{ "questions": [ { "body": "Is Hirschsprung disease a mendelian or a multifactorial disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15858239", "http://www.ncbi.nlm.nih.gov/pubmed/15829955", "http://www.ncbi.nlm.nih.gov/pubmed/6650562", "http://www.ncbi.nlm.nih.gov/pubmed/12239580", "http://www.ncbi.nlm.nih.gov/pubmed/21995290", "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "http://www.ncbi.nlm.nih.gov/pubmed/15617541", "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "http://www.ncbi.nlm.nih.gov/pubmed/20598273" ], "ideal_answer": [ "Coding sequence mutations in RET, GDNF, EDNRB, EDN3, and SOX10 are involved in the development of Hirschsprung disease. The majority of these genes was shown to be related to Mendelian syndromic forms of Hirschsprung's disease, whereas the non-Mendelian inheritance of sporadic non-syndromic Hirschsprung disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10487", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020412", "http://www.disease-ontology.org/api/metadata/DOID:11372" ], "type": "summary", "id": "55031181e9bde69634000014", "snippets": [ { "offsetInBeginSection": 131, "offsetInEndSection": 358, "text": "Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15829955", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 992, "text": "In this study, we review the identification of genes and loci involved in the non-syndromic common form and syndromic Mendelian forms of Hirschsprung's disease. The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease. The non-Mendelian inheritance of sporadic non-syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15617541", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 939, "text": "Coding sequence mutations in e.g. RET, GDNF, EDNRB, EDN3, and SOX10 lead to long-segment (L-HSCR) as well as syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). Furthermore, mutations in the RET gene are responsible for approximately half of the familial and some sporadic cases, strongly suggesting, on the one hand, the importance of non-coding variations and, on the other hand, that additional genes involved in the development of the enteric nervous system still await their discovery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12239580", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1279, "text": "For almost all of the identified HSCR genes incomplete penetrance of the HSCR phenotype has been reported, probably due to modifier loci. Therefore, HSCR has become a model for a complex oligo-/polygenic disorder in which the relationship between different genes creating a non-mendelian inheritance pattern still remains to be elucidated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12239580", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 358, "text": " Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15829955", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1007, "text": " The inheritance of Hirschsprung disease is generally consistent with sex-modified multifactorial inheritance with a lower threshold of expression in males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6650562", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 359, "text": "Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15829955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598273", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "BACKGROUND: RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21995290", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 376, "text": "In the etiology of Hirschsprung disease various genes play a role; these are: RET, EDNRB, GDNF, EDN3 and SOX10, NTN3, ECE1, Mutations in these genes may result in dominant, recessive or multifactorial patterns of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15858239", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Chromosomal and related Mendelian syndromes associated with Hirschsprung's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "endSection": "title" }, { "offsetInBeginSection": 715, "offsetInEndSection": 818, "text": "The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15617541", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 375, "text": "In the etiology of Hirschsprung disease various genes play a role; these are: RET, EDNRB, GDNF, EDN3 and SOX10, NTN3, ECE1, Mutations in these genes may result in dominant, recessive or multifactorial patterns of inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15858239", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 615, "text": "On the basis of a skewed sex-ratio (M/F = 4/1) and a risk to relatives much higher than the incidence in the general population, HSCR has long been regarded as a sex-modified multifactorial disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1012, "text": "The inheritance of Hirschsprung disease is generally consistent with sex-modified multifactorial inheritance with a lower threshold of expression in males", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6650562", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 992, "text": "The non-Mendelian inheritance of sporadic non-syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15617541", "endSection": "abstract" } ] }, { "body": "List signaling molecules (ligands) that interact with the receptor EGFR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23959273", "http://www.ncbi.nlm.nih.gov/pubmed/21514161", "http://www.ncbi.nlm.nih.gov/pubmed/23212918", "http://www.ncbi.nlm.nih.gov/pubmed/23888072", "http://www.ncbi.nlm.nih.gov/pubmed/23821377", "http://www.ncbi.nlm.nih.gov/pubmed/23099994", "http://www.ncbi.nlm.nih.gov/pubmed/22260327", "http://www.ncbi.nlm.nih.gov/pubmed/24204699", "http://www.ncbi.nlm.nih.gov/pubmed/24323361", "http://www.ncbi.nlm.nih.gov/pubmed/23089711", "http://www.ncbi.nlm.nih.gov/pubmed/23399900", "http://www.ncbi.nlm.nih.gov/pubmed/23382875", "http://www.ncbi.nlm.nih.gov/pubmed/23729230", "http://www.ncbi.nlm.nih.gov/pubmed/23787814", "http://www.ncbi.nlm.nih.gov/pubmed/24124521", "http://www.ncbi.nlm.nih.gov/pubmed/22247333" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q9QX70", "o": "http://linkedlifedata.com/resource/#_5139515837300022" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5139515837300022", "o": "Egfr" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/intact/EBI-1256812", "o": "http://purl.uniprot.org/uniprot/Q9QX70" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-1256812", "o": "Egfr" } ], "ideal_answer": [ "The 7 known EGFR ligands are: epidermal growth factor (EGF), betacellulin (BTC), epiregulin (EPR), heparin-binding EGF (HB-EGF), transforming growth factor-\u03b1 [TGF-\u03b1], amphiregulin (AREG) and epigen (EPG)." ], "exact_answer": [ [ "epidermal growth factor" ], [ "betacellulin" ], [ "epiregulin" ], [ "heparin-binding epidermal growth factor" ], [ "transforming growth factor-\u03b1" ], [ "amphiregulin" ], [ "epigen" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005154", "http://www.uniprot.org/uniprot/EGFR_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005488", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042058", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018773", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008024", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045741", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007173", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005006", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007175", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007176", "http://www.uniprot.org/uniprot/EGFR_CHICK" ], "type": "list", "id": "55046d5ff8aee20f27000007", "snippets": [ { "offsetInBeginSection": 1085, "offsetInEndSection": 1199, "text": "the epidermal growth factor receptor (EGFR) ligands, such as epidermal growth factor (EGF) and amphiregulin (AREG)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24323361", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1247, "text": " EGFR ligands epidermal growth factor (EGF), amphiregulin (AREG) and transforming growth factor alpha (TGF\u03b1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24124521", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 97, "text": " EGFR and its ligand EGF ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23959273", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1058, "text": "Among EGFR ligands, heparin-binding EGF-like growth factor, TGF-\u03b1 and Betacellulin (BTC) are produced in the tumor microenvironment of FDC-S at RNA level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23888072", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 493, "text": ". Plasma amphiregulin (AR), epidermal growth factor (EGF), transforming growth factor-\u03b1, and heparin binding-EGF were assessed by ELISA in 45 chemorefractory mCRC patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821377", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 414, "text": "Among EGFR ligands, heparin-binding epidermal growth factor (HB-EGF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787814", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 521, "text": " Of the six known EGFR ligands, transforming growth factor alpha (TGF\u03b1) was expressed more highly in triple-negative breast tumors than in tumors of other subtypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729230", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 923, "text": "the 7 known EGFR ligands (EGF, betacellulin, epiregulin, heparin-binding EGF, transforming growth factor-\u03b1 [TGF-\u03b1], amphiregulin, and epigen) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23399900", "endSection": "abstract" }, { "offsetInBeginSection": 1393, "offsetInEndSection": 1472, "text": "EGFR ligands based on the two affinity classes: EGF>HB-EGF>TGF-\u03b1>BTC>EPR>EPG>AR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382875", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 320, "text": "In this article, however, we demonstrate that PEPD directly binds to and activates epidermal growth factor receptor (EGFR),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212918", "endSection": "abstract" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1607, "text": "four EGFR ligands (AR, HB-EGF, TGF-\u03b1, and EREG) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Epidermal growth factor (EGF) family peptides are ligands for the EGF receptor (EGFR). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22260327", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 490, "text": "oluble amphiregulin (AR), transforming growth factor alpha (TGF\u03b1), neuregulin 2 beta, and epigen stimulate greater EGFR coupling to cell proliferation and DNA synthesis than do EGF, betacellulin, heparin-binding EGF-like growth factor, and epiregulin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22260327", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 563, "text": "Here, we demonstrate that histamine releases 2 EGFR ligands, amphiregulin and heparin-binding epidermal growth factor-like growth factor (HB-EGF), from airway epithelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247333", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 231, "text": "mammalian EGFR ligands including EGF, TGF-\u03b1 (TGF\u03b1), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin, epiregulin, and epigen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21514161", "endSection": "abstract" } ] }, { "body": "Is the protein Papilin secreted?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3320045", "http://www.ncbi.nlm.nih.gov/pubmed/7515725", "http://www.ncbi.nlm.nih.gov/pubmed/20805556", "http://www.ncbi.nlm.nih.gov/pubmed/19297413", "http://www.ncbi.nlm.nih.gov/pubmed/19724244", "http://www.ncbi.nlm.nih.gov/pubmed/15094122", "http://www.ncbi.nlm.nih.gov/pubmed/12666201", "http://www.ncbi.nlm.nih.gov/pubmed/21784067", "http://www.ncbi.nlm.nih.gov/pubmed/11076767", "http://www.ncbi.nlm.nih.gov/pubmed/15094110" ], "ideal_answer": [ "Yes, papilin is a secreted protein" ], "exact_answer": "yes", "type": "yesno", "id": "54e25eaaae9738404b000017", "snippets": [ { "offsetInBeginSection": 1085, "offsetInEndSection": 1307, "text": "Using expression analysis, we identify three genes that are transcriptionally regulated by HLH-2: the protocadherin cdh-3, and two genes encoding secreted extracellular matrix proteins, mig-6/papilin and him-4/hemicentin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21784067", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 458, "text": "We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297413", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 111, "text": "apilins are homologous, secreted extracellular matrix proteins which share a common order of protein domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15094122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "The TSR superfamily is a diverse family of extracellular matrix and transmembrane proteins, many of which have functions related to regulating matrix organization, cell-cell interactions and cell guidance. This review samples some of the contemporary literature regarding TSR superfamily members (e.g. F-spondin, UNC-5, ADAMTS, papilin, and TRAP) where specific functions are assigned to the TSR domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15094110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Papilins are extracellular matrix proteins ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12666201", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Papilin is an extracellular matrix glycoprotein ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11076767", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 882, "text": " Collagen IV, laminin, glutactin, papilin, and other extracellular matrix proteins were made primarily by hemocytes and were secreted into the medium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7515725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "A sulfated glycoprotein was isolated from the culture media of Drosophila Kc cells and named papilin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3320045", "endSection": "abstract" } ] }, { "body": "Are long non coding RNAs spliced?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "http://www.ncbi.nlm.nih.gov/pubmed/22955974", "http://www.ncbi.nlm.nih.gov/pubmed/24285305", "http://www.ncbi.nlm.nih.gov/pubmed/22707570", "http://www.ncbi.nlm.nih.gov/pubmed/21622663", "http://www.ncbi.nlm.nih.gov/pubmed/24106460" ], "ideal_answer": [ "Long non coding RNAs appear to be spliced through the same pathway as the mRNAs" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085" ], "type": "yesno", "id": "535d292a9a4572de6f000003", "snippets": [ { "offsetInBeginSection": 546, "offsetInEndSection": 739, "text": "Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "abstract" }, { "offsetInBeginSection": 1602, "offsetInEndSection": 1732, "text": "For alternative exons and long noncoding RNAs, splicing tends to occur later, and the latter might remain unspliced in some cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955974", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 557, "text": "bosome-mapping data to identify lncRNAs of Caenorhabditis elegans. We found 170 long intervening ncRNAs (lincRNAs), which had single- or multiexonic structures that did not overlap protein-coding transcripts, and about sixty antisense lncRNAs (ancRNAs), which were complementary to protein-coding transcripts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707570", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 401, "text": "We introduce an approach to predict spliced lncRNAs in vertebrate genomes combining comparative genomics and machine learning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21622663", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 856, "text": "Owing to similar alternative splicing pattern to mRNAs, the concept of lncRNA genes was put forward to help systematic understanding of lncRNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285305", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 746, "text": "Our synthesis of recent studies suggests that neither size, presence of a poly-A tail, splicing, direction of transcription, nor strand specificity are of importance to lncRNA function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106460", "endSection": "abstract" } ] }, { "body": "Is RANKL secreted from the cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21618594", "http://www.ncbi.nlm.nih.gov/pubmed/23698708", "http://www.ncbi.nlm.nih.gov/pubmed/23827649", "http://www.ncbi.nlm.nih.gov/pubmed/22901753", "http://www.ncbi.nlm.nih.gov/pubmed/22948539", "http://www.ncbi.nlm.nih.gov/pubmed/23835909", "http://www.ncbi.nlm.nih.gov/pubmed/23632157", "http://www.ncbi.nlm.nih.gov/pubmed/24265865", "http://www.ncbi.nlm.nih.gov/pubmed/24267510", "http://www.ncbi.nlm.nih.gov/pubmed/22867712" ], "ideal_answer": [ "Receptor activator of nuclear factor \u03baB ligand (RANKL) is a cytokine predominantly secreted by osteoblasts." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/TNF11_RAT", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870", "http://www.uniprot.org/uniprot/TNF11_HUMAN" ], "type": "yesno", "id": "55262a9787ecba3764000009", "snippets": [ { "offsetInBeginSection": 114, "offsetInEndSection": 242, "text": "Osteoprotegerin (OPG) is a soluble secreted factor that acts as a decoy receptor for receptor activator of NF-\u03baB ligand (RANKL) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24267510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily. It usually functions in bone remodeling, by inhibiting osteoclastogenesis through interaction with a receptor activator of the nuclear factor \u03baB (RANKL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265865", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1247, "text": "e RANKL/OPG ratio secreted by osteoblasts increased and RANK expression by osteoclasts increased, leading to increased osteoclastogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23835909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Osteoprotegerin (OPG) is an essential secreted protein in bone turnover due to its role as a decoy receptor for the Receptor Activator of Nuclear Factor-kB ligand (RANKL) in the osteoclasts, thus inhibiting their differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23827649", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 439, "text": "We identify a TNFSF11 transcript variant that extends the originally identified transcript encoding secreted RANKL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23698708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23698708", "endSection": "title" }, { "offsetInBeginSection": 471, "offsetInEndSection": 621, "text": "OPG, on the other hand, is secreted by osteoblast as a decoy receptor for RANKL, prevents RANKL from binding to RANK and thus prevents bone resorption", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23632157", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 486, "text": "Receptor activator of nuclear factor \u03baB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22948539", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 1005, "text": "Although B. abortus-activated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22901753", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 758, "text": " osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22867712", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 478, "text": "Osteoprotegerin (OPG) and receptor activator of nuclear factor \u03baB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21618594", "endSection": "abstract" } ] }, { "body": "Does metformin interfere thyroxine absorption?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26191653" ], "ideal_answer": [ "No. There are not reported data indicating that metformin reduce with thyroxine absorption." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008687", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000042" ], "type": "yesno", "id": "51406e6223fec90375000009", "snippets": [ { "offsetInBeginSection": 1418, "offsetInEndSection": 1481, "text": "LT4 absorption is unchanged by concomitant metformin ingestion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26191653", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 302, "text": "It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic-pituitary axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26191653", "endSection": "abstract" } ] }, { "body": "Which miRNAs could be used as potential biomarkers for epithelial ovarian cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21345725", "http://www.ncbi.nlm.nih.gov/pubmed/22246341", "http://www.ncbi.nlm.nih.gov/pubmed/23836287", "http://www.ncbi.nlm.nih.gov/pubmed/20035894", "http://www.ncbi.nlm.nih.gov/pubmed/23542579", "http://www.ncbi.nlm.nih.gov/pubmed/19074899", "http://www.ncbi.nlm.nih.gov/pubmed/21971665", "http://www.ncbi.nlm.nih.gov/pubmed/23978303", "http://www.ncbi.nlm.nih.gov/pubmed/18954897", "http://www.ncbi.nlm.nih.gov/pubmed/21571355", "http://www.ncbi.nlm.nih.gov/pubmed/23888941", "http://www.ncbi.nlm.nih.gov/pubmed/23918241", "http://www.ncbi.nlm.nih.gov/pubmed/23272653", "http://www.ncbi.nlm.nih.gov/pubmed/23621186" ], "ideal_answer": [ "miR-200a, miR-100, miR-141, miR-200b, miR-200c, miR-203, miR-510, miR-509-5p, miR-132, miR-26a, let-7b, miR-145, miR-182, miR-152, miR-148a, let-7a, let-7i, miR-21, miR-92 and miR-93 could be used as potential biomarkers for epithelial ovarian cancer." ], "exact_answer": [ [ "let-7a" ], [ "let-7b" ], [ "let-7i" ], [ "miR-21" ], [ "miR-26a" ], [ "miR-92" ], [ "miR-93" ], [ "miR-100" ], [ "miR-132" ], [ "miR-141" ], [ "miR-145" ], [ "miR-148a" ], [ "miR-152" ], [ "miR-182" ], [ "miR-200a" ], [ "miR-200b" ], [ "miR-200c" ], [ "miR-203" ], [ "miR-509-5p" ], [ "miR-510" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010051", "http://www.disease-ontology.org/api/metadata/DOID:2394" ], "type": "list", "id": "553fa78b1d53b76422000007", "snippets": [ { "offsetInBeginSection": 1010, "offsetInEndSection": 1388, "text": "Finally, five promising differentially miRNAs (miR-200a, miR-100, miR-141, miR-200b, and miR-200c) were reported with the consistent direction in four or more studies. MiR-200a, miR-200b, miR-200c, and miR-141, all of them belong to miR-200 family, were reported with consistently up-regulated in at least 4 studies, whereas miR-100 was reported with down-regulated in 4 studies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23978303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918241", "endSection": "title" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1418, "text": "multivariate analysis showed that the status of miR-203 expression was an independent predictor for both overall survival and progression-free survival in EOC. These findings provide the convincing evidence for the first time that the upregulation of miR-203 may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of EOC patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918241", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 773, "text": "Some, but not all, of the data indicated that the miR-200 family was dysregulated in a variety of malignancies. In this study, we demonstrated that miR-200a and E-cadherin were significantly upregulated in EOC compared to benign epithelial ovarian cysts and normal ovarian tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23888941", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1656, "text": "There was a significantly positive correlation between miR-200a and E-cadherin in EOC. The biphasic expression pattern suggested that miR-200a levels may serve as novel biomarkers for the early detection of EOC, and miR-200a and E-cadherin are candidate targets for the development of new treatment modalities against ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23888941", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1771, "text": "Kaplan-Meier analysis showed low miR-510 expression, low miR-509-5p expression, and advanced FIGO stage, and chemotherapy resistance were significantly associated with poorer overall survival (P < 0.05). Our results suggest that miRNAs may play a role in the progression of OSC, and miR-510 and miR-509-5p may be considered novel-candidate clinical biomarkers for predicting OSC outcome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836287", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1383, "text": "The qRT-PCR results showed that miR-510, miR-509-5p, and miR-508-3p were significantly downregulated and that miR-483-5p was upregulated in stage III OSC compared with stage I, which was consistent with the microarray results", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836287", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 704, "text": "In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621186", "endSection": "title" }, { "offsetInBeginSection": 1680, "offsetInEndSection": 1813, "text": "Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23542579", "endSection": "abstract" }, { "offsetInBeginSection": 1173, "offsetInEndSection": 1665, "text": "Among the miRNAs that showed a consistent regulation tendency through all specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132, miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly down-regulated miRNAs in the serum from ovarian cancer patients with respect to those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5 selected miRNAs were significantly underexpressed in the serum of ovarian cancer patients in qRT-PCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23542579", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 968, "text": " microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272653", "endSection": "abstract" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1633, "text": "Together, these results suggest that low miR-100 expression may be an independent poor prognostic factor and miR-100 can function as a tumor suppressor by targeting PLK1 in human EOCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246341", "endSection": "title" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1738, "text": "Taken together, miR-152 and miR-148a may be involved in the carcinogenesis of ovarian cancer through deregulation of cell proliferation. They may be novel biomarkers for early detection or therapeutic targets of ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21971665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "MicroRNA let-7a: a potential marker for selection of paclitaxel in ovarian cancer management", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21571355", "endSection": "title" }, { "offsetInBeginSection": 1988, "offsetInEndSection": 2236, "text": " The study suggests that the beneficial impact of the addition of paclitaxel on EOC survival was significantly linked to let-7a levels, and that miRNAs such as let-7a may be a useful marker for selection of chemotherapeutic agents in EOC management", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21571355", "endSection": "abstract" }, { "offsetInBeginSection": 2573, "offsetInEndSection": 2669, "text": "miR-200c has potential as a predictor of survival, and is a biomarker of relapse, in stage I EOC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21345725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074899", "endSection": "title" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1723, "text": " our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074899", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1641, "text": "miRNAs-21, 92 and 93 are known oncogenes with therapeutic and biomarker potential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18954897", "endSection": "abstract" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1773, "text": "Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23542579", "endSection": "abstract" } ] }, { "body": "Which acetylcholinesterase inhibitors are used for treatment of myasthenia gravis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21815707", "http://www.ncbi.nlm.nih.gov/pubmed/21845054", "http://www.ncbi.nlm.nih.gov/pubmed/21328290", "http://www.ncbi.nlm.nih.gov/pubmed/20663605", "http://www.ncbi.nlm.nih.gov/pubmed/21133188", "http://www.ncbi.nlm.nih.gov/pubmed/15610702" ], "ideal_answer": [ "Pyridostigmine and neostygmine are acetylcholinesterase inhibitors that are used as first-line therapy for symptomatic treatment of myasthenia gravis. Pyridostigmine is the most widely used acetylcholinesterase inhibitor. Extended release pyridotsygmine and novel acetylcholinesterase inhibitors inhibitors with oral antisense oligonucleotides are being studied." ], "exact_answer": [ [ "neostigmine" ], [ "pyridostigmine" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000110", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002800", "http://www.disease-ontology.org/api/metadata/DOID:437", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009157", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ], "type": "list", "id": "5149199dd24251bc05000040", "snippets": [ { "offsetInBeginSection": 1251, "offsetInEndSection": 1321, "text": "Pyridostigmine is the most widely used acetylcholinesterase inhibitor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21133188", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 171, "text": "For more than 50 years the acetylcholinesterase inhibitor pyridostigmine bromide has been the drug of choice in the symptomatic therapy for myasthenia gravis. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20663605", "endSection": "sections.0" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1229, "text": "The switch to SR-Pyr ameliorated the total quantified myasthenia gravis (QMG) score from 0.9 \u00b1 0.5 to 0.6 \u00b1 0.4 (p<0.001) in all patients and in the younger subgroup. This was accompanied by a significant improvement in the quality of life parameters. The health status valued by EuroQoL questionnaire improved from 0.626 \u00b1 0.286 to 0.782 \u00b1 0.186 (p<0.001). ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20663605", "endSection": "sections.0" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1578, "text": "Our results support the usefulness of SR-Pyr in an individualized therapeutic regimen to improve quality of life regardless of the patient's age in myasthenia gravis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20663605", "endSection": "sections.0" }, { "offsetInBeginSection": 476, "offsetInEndSection": 571, "text": "This review focuses on treatment of MG, mainly on the use of the AChE inhibitor pyridostigmine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815707", "endSection": "sections.0" }, { "offsetInBeginSection": 572, "offsetInEndSection": 768, "text": "Despite a lack of data from well controlled clinical trials to support their use, AChE inhibitors, of which pyridostigmine is the most commonly used, are recommended as first-line therapy for MG. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815707", "endSection": "sections.0" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1197, "text": "Novel AChE inhibitors with oral antisense oligonucleotides have been developed and preliminary results appear to be promising.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815707", "endSection": "sections.0" }, { "offsetInBeginSection": 2418, "offsetInEndSection": 2808, "text": "Except for one small and inconclusive trial of intranasal neostigmine, no randomised controlled trial has been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. Response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in the placebo arm of treatment would be difficult to justify.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21328290", "endSection": "sections.0" }, { "offsetInBeginSection": 178, "offsetInEndSection": 475, "text": " Current guidelines and recommendations for MG treatment are based largely on clinical experience, retrospective analyses and expert consensus. Available therapies include oral acetylcholinesterase (AChE) inhibitors for symptomatic treatment, and short- and long-term disease-modifying treatments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815707", "endSection": "sections.0" }, { "offsetInBeginSection": 768, "offsetInEndSection": 1071, "text": "Pyridostigmine has been used as a treatment for MG for over 50 years and is generally considered safe. It is suitable as a long-term treatment in patients with generalized non-progressive milder disease, and as an adjunctive therapy in patients with severe disease who are also receiving immunotherapy. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815707", "endSection": "sections.0" }, { "offsetInBeginSection": 343, "offsetInEndSection": 452, "text": "Acetylcholinesterase inhibitors provide temporary, symptomatic treatment for all forms of myasthenia gravis. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15610702", "endSection": "sections.0" } ] }, { "body": "Has Denosumab (Prolia) been approved by FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24126422", "http://www.ncbi.nlm.nih.gov/pubmed/22826702", "http://www.ncbi.nlm.nih.gov/pubmed/21208140", "http://www.ncbi.nlm.nih.gov/pubmed/21113693", "http://www.ncbi.nlm.nih.gov/pubmed/21129866", "http://www.ncbi.nlm.nih.gov/pubmed/23956508", "http://www.ncbi.nlm.nih.gov/pubmed/22716221", "http://www.ncbi.nlm.nih.gov/pubmed/23757624", "http://www.ncbi.nlm.nih.gov/pubmed/23367751", "http://www.ncbi.nlm.nih.gov/pubmed/22074657", "http://www.ncbi.nlm.nih.gov/pubmed/21785279", "http://www.ncbi.nlm.nih.gov/pubmed/21942303", "http://www.ncbi.nlm.nih.gov/pubmed/24114694", "http://www.ncbi.nlm.nih.gov/pubmed/22540167", "http://www.ncbi.nlm.nih.gov/pubmed/24308016", "http://www.ncbi.nlm.nih.gov/pubmed/21170699", "http://www.ncbi.nlm.nih.gov/pubmed/23652187", "http://www.ncbi.nlm.nih.gov/pubmed/23759273", "http://www.ncbi.nlm.nih.gov/pubmed/21470540", "http://www.ncbi.nlm.nih.gov/pubmed/24316116", "http://www.ncbi.nlm.nih.gov/pubmed/20811384" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18043383", "o": "FDA Structured Product Labels" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A17995522" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11914653", "o": "Densosumab" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A18043383" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A18087179" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12802315", "o": "Denosumab" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A18084860" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A12802315" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A9373021" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A11920279" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A17699205" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1690432", "o": "http://linkedlifedata.com/resource/umls/label/A11914653" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18043383", "o": "DENOSUMAB" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11920279", "o": "denosumab" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2917754", "o": "http://linkedlifedata.com/resource/umls/id/C1690432" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18043386", "o": "Prolia" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17995522", "o": "993449" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11914653", "o": "CDR0000481348" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11920279", "o": "CDR0000481348" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18087179", "o": "27218" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17995522", "o": "RXNORM" } ], "ideal_answer": [ "Yes, Denosumab was approved by the FDA in 2010." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4268082" ], "type": "yesno", "id": "52bf1db603868f1b06000011", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 177, "text": "Denosumab is a RANK-ligand antibody that was approved by the FDA in 2010 for the prevention of skeletal fractures in patients with bone metastases from solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24316116", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 1261, "text": " The authors present the imaging findings and technical report of an attempted percutaneous vertebroplasty in the only patient found to be actively under treatment with denosumab after a retrospective review of the databank of patients with pathological fractures referred to the Department Radiology of the Ohio State University for percutaneous vertebroplasty (a total sample of 20 patients) since the FDA approval of denosumab (November 2010) until June of 2013 (a 30-month period).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24316116", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 769, "text": "On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24308016", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 816, "text": "Denosumab (Prolia\u00ae) is a fully human monoclonal antibody for RANKL, which selectively inhibits osteoclastogenesis, being recently approved for the treatment of postmenopausal osteoporosis in women at a high or increased risk of fracture by the FDA in the United Sates and by the European Medicines Agency in Europe since June 2010.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24126422", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 999, "text": "Recent phase II clinical trials with denosumab in skeletally mature adolescents over age 12 years and adults with GCTB, have shown both safety and efficacy, leading to its accelerated US FDA approval on 13 June 2013. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114694", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1016, "text": "Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23956508", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 970, "text": "These results led to the approval of denosumab by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), for the prevention of SREs in adults with bone metastases from solid tumors, including breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23759273", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1210, "text": "Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23757624", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1196, "text": "Several of these therapies have recently been approved by the FDA to treat bone cancer pain (bisphosphonates, denosumab) and others are currently being evaluated in human clinical trials (tanezumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652187", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1086, "text": "A fourth agent, denosumab (bone targeted therapy) was also recently approved by the FDA for patients with bone metastasis after showing a reduction in the occurrence of skeletal-related events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23367751", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 968, "text": "AHRQ published an updated review in March 2012 that summarized the benefits and risks of osteoporosis medications in treatment and prevention of osteoporosis, including bisphosphonates (aledronate, risedronate, ibandronate, zoledronic acid), parathyroid hormone, teriparatide, calcitonin, estrogens (for prevention in postmenopausal women), selective estrogen receptor modulators (raloxifene), and denosumab(approved by the FDA in 2010). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22716221", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 1029, "text": "Four new drugs have received U.S. Food and Drug Administration (FDA)-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22826702", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 326, "text": "Recently, the US FDA and the EMA approved denosumab (a fully human monoclonal antibody) to treat skeletal-related events in bone-metastatic prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540167", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1260, "text": "In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22074657", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 798, "text": "Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21942303", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 604, "text": "In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21785279", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 562, "text": "We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470540", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 546, "text": " It has been approved for clinical use by the FDA in the US and by the European Medicines Agency in Europe since June 2010 (trade name Prolia(\u2122), Amgen, Thousand Oaks, CA, USA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208140", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 363, "text": "The fully human monoclonal antibody denosumab (Prolia(\u00ae)) has been recently approved by the European Medical Agency (EMEA) and the Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21170699", "endSection": "abstract" }, { "offsetInBeginSection": 1321, "offsetInEndSection": 1400, "text": "Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21129866", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 936, "text": "The new antiresorptive drug, denosumab, although FDA-approved only for postmenopausal women, has been shown in a study of men on ADT to increase bone density in spine, hip, and forearm and decrease vertebral fractures on x-ray. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21113693", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 665, "text": " Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811384", "endSection": "abstract" } ] }, { "body": "List the human genes encoding for the dishevelled proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12883684", "http://www.ncbi.nlm.nih.gov/pubmed/24040443", "http://www.ncbi.nlm.nih.gov/pubmed/19618470", "http://www.ncbi.nlm.nih.gov/pubmed/8817329", "http://www.ncbi.nlm.nih.gov/pubmed/8856345", "http://www.ncbi.nlm.nih.gov/pubmed/23836490", "http://www.ncbi.nlm.nih.gov/pubmed/8149913", "http://www.ncbi.nlm.nih.gov/pubmed/7958461", "http://www.ncbi.nlm.nih.gov/pubmed/16457155" ], "ideal_answer": [ "DVL-1\nDVL-2\nDVL-3" ], "exact_answer": [ [ "DVL-1" ], [ "DVL-2" ], [ "DVL-3" ] ], "type": "list", "id": "5709e4b2cf1c32585100001c", "snippets": [ { "offsetInBeginSection": 294, "offsetInEndSection": 516, "text": "Dishevelled (Dvl/Dsh) is a multi-module protein and a key regulator of both the canonical Wnt and the PCP pathway. In mouse, all Dvl1(-/-) ; Dvl2(-/-) double mutants display craniorachischisis, a severe form of open NTDs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836490", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 511, "text": " In this study, we explore the cause of HSCR by studying the expression of DVL-1 and DVL-3 genes and their proteins in the aganglionic segment and the ganglionic segment of colon in HSCR patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Dishevelled (Dvl) proteins are key transducers of Wnt signaling encoded by members of a multi-gene family in vertebrates. We report here the divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression patterns in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19618470", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 346, "text": "velopmental processes, including segmentation and neuroblast specification. We have isolated and characterized cDNA clones from two different human dsh-homologous genes, designated as DVL-1 and DVL-3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8817329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "In the Drosophila embryo dishevelled (dsh) function is required by target cells in order to respond to wingless (wg, the homolog of Wnt-1), demonstrating a role for dsh in Wnt signal transduction. We have isolated a mouse homolog of the Drosophila dsh segment polarity gene. The 695-amino-acid protein encoded by the mouse dishevelled gene (Dvl-1) shares 50% identity (65% similarity) with dsh.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7958461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "The Dvl-1 gene on chromosome 1p36 belongs to a family of highly conserved secreted proteins which regulates embryonic induction, generation of cell polarity and specification of cell fate through activation of Wnt signaling pathways. Wnt signaling activates the gene encoding DVL-1;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12883684", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 629, "text": "We report here that the mouse Dishevelled-1 (Dvl-1) and Dishevelled-2 genes encode proteins that are differentially localized in Wnt-overexpressing PC12 cell lines (PC12/Wnt). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8856345", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 255, "text": "Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta-catenin signaling pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16457155", "endSection": "abstract" } ] }, { "body": "Name synonym of Acrokeratosis paraneoplastica.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3819049", "http://www.ncbi.nlm.nih.gov/pubmed/18775590", "http://www.ncbi.nlm.nih.gov/pubmed/6225397", "http://www.ncbi.nlm.nih.gov/pubmed/22146896", "http://www.ncbi.nlm.nih.gov/pubmed/7796616", "http://www.ncbi.nlm.nih.gov/pubmed/18672707", "http://www.ncbi.nlm.nih.gov/pubmed/16435144", "http://www.ncbi.nlm.nih.gov/pubmed/7640201", "http://www.ncbi.nlm.nih.gov/pubmed/22252191", "http://www.ncbi.nlm.nih.gov/pubmed/17097409", "http://www.ncbi.nlm.nih.gov/pubmed/17374318", "http://www.ncbi.nlm.nih.gov/pubmed/22470801", "http://www.ncbi.nlm.nih.gov/pubmed/8949310", "http://www.ncbi.nlm.nih.gov/pubmed/1521479", "http://www.ncbi.nlm.nih.gov/pubmed/1433123" ], "ideal_answer": [ "Acrokeratosis paraneoplastic (Bazex syndrome) is a rare, but distinctive paraneoplastic dermatosis characterized by erythematosquamous lesions located at the acral sites and is most commonly associated with carcinomas of the upper aerodigestive tract." ], "exact_answer": [ "Bazex syndrome" ], "type": "factoid", "id": "56bc751eac7ad10019000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Acrokeratosis paraneoplastica of Bazex is a rare but important paraneoplastic dermatosis, usually manifesting as psoriasiform rashes over the acral sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22252191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "[Paraneoplastic palmoplantar hyperkeratosis. Minor form of acrokeratosis neoplastica Bazex?].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22146896", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Acrokeratosis paraneoplastica Bazex is a rare, obligate paraneoplasia initially presenting with palmoplantar hyperkeratosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22146896", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 529, "text": "We diagnosed a minor form of acrokeratosis paraneoplastica Bazex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22146896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Acrokeratosis paraneoplastica (Bazex syndrome): report of a case associated with small cell lung carcinoma and review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22470801", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Acrokeratosis paraneoplastic (Bazex syndrome) is a rare, but distinctive paraneoplastic dermatosis characterized by erythematosquamous lesions located at the acral sites and is most commonly associated with carcinomas of the upper aerodigestive tract. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22470801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Bazex syndrome (acrokeratosis paraneoplastica): persistence of cutaneous lesions after successful treatment of an associated oropharyngeal neoplasm.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18775590", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Acrokeratosis paraneoplastica Bazex syndrome associated with esophageal squamocellular carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18672707", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "BACKGROUND: Acrokeratosis paraneoplastica Bazex (APB) is a very rare disease in the group of obligate paraneoplastic dermatoses, associated mostly with squamous cell carcinoma of the upper aerodigestive tract and metastatic cervical lymphadenopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18672707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Acrokeratosis paraneoplastica (Bazex' syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3819049", "endSection": "title" }, { "offsetInBeginSection": 362, "offsetInEndSection": 1122, "text": "Acrokeratosis paraneoplastica (first described by Gougerot and Rupp in 1922) was named after Bazex who had then reported several cases in a French dermatological journal since 1965 (Bazex et al. in Bull Soc Fr Dermatol Syphiligr 72:182, 1965; Bazex and Griffiths in Br J Dermatol 102:301-306, 1980).METHOD: The study is a clinical case of a patient with acrokeratosis paraneoplastica.RESULTS: the patient was later diagnosed with a cervical lymph node metastasis and thereafter with a primary squamous cell carcinoma of the left upper lobe and upon treatment responded with the clearing of the skin changes.CONCLUSION: Identification of a paraneoplastic syndrome may enhance the earlier diagnosis of the associated tumor and may thus enable curative treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16435144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Acrokeratosis paraneoplastica (Bazex's syndrome): association with liposarcoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17097409", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Acrokeratosis paraneoplastica of Bazex as an indicator for underlying squamous cell carcinoma of the lung.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16435144", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Acrokeratosis paraneoplastica (Bazex syndrome) with oropharyngeal squamous cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7796616", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Acrokeratosis paraneoplastica of Bazex: report of a case in a young black woman.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1521479", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Acrokeratosis paraneoplastica of Bazex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1433123", "endSection": "title" }, { "offsetInBeginSection": 354, "offsetInEndSection": 548, "text": "Acrokeratosis paraneoplastica (first described by Gougerot and Rupp in 1922) was named after Bazex who had then reported several cases in a French dermatological journal since 1965 (Bazex et al.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16435144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Acrokeratosis paraneoplastica: Bazex syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8949310", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Bazex syndrome: acrokeratosis paraneoplastica.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7640201", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 405, "text": "Acrokeratosis paraneoplastica (Bazex' syndrome) is a rare but clinically distinctive dermatosis that has been associated in all reported cases, to our knowledge, with either a primary malignant neoplasm of the upper aerodigestive tract or metastatic cancer to the lymph nodes of the neck. Acrokeratosis paraneoplastica was found in a 53-year-old black man with squamous cell carcinoma of the tonsil.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6225397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 501, "text": "Bazex syndrome (acrokeratosis paraneoplastica) is a rare paraneoplastic syndrome that usually occurs in males over 40 years old and is particularly associated with squamous cell carcinoma of the upper aerodigestive tract and adenopathy above the diaphragm.The objectives of our article are (1) to describe a unique case of acrokeratosis paraneoplastica and (2) to review the current literature regarding skin findings, commonly associated neoplasms, and treatment options relative to this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17374318", "endSection": "abstract" } ] }, { "body": "Which are the classes of anti-arrhythmic drugs according to Vaughan-Williams classification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9803978", "http://www.ncbi.nlm.nih.gov/pubmed/11564050", "http://www.ncbi.nlm.nih.gov/pubmed/1290288", "http://www.ncbi.nlm.nih.gov/pubmed/7875632", "http://www.ncbi.nlm.nih.gov/pubmed/10810787" ], "ideal_answer": [ "Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV). Class I antiarrhythmic agents have as a common action, blockade of the sodium channels. Class II agents are antisympathetic drugs, particularly the beta-adrenoceptor blockers. Class-III antiarrhythmics have as a common action the potassium-channel blockade. Class IV antiarrhythmic drugs are calcium channel blockers." ], "exact_answer": [ [ "Class I: sodium channel blockers" ], [ "ClassII: beta blockers" ], [ "Class III: potassium channel blockers" ], [ "Class IV: calcium channel blockers" ] ], "type": "list", "id": "54d4e03a3706e89528000001", "snippets": [ { "offsetInBeginSection": 491, "offsetInEndSection": 577, "text": "Class II agents are antisympathetic drugs, particularly the beta-adrenoceptor blockers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9803978", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 709, "text": "Class III antiarrhythmic agents include sotalol and amiodarone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9803978", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 923, "text": "Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9803978", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1111, "text": "Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9803978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV) according to defined electrophysiological effects on the myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10810787", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 350, "text": "Thus, the Vaughan Williams classification also coincides with the main myocardial targets of the antiarrhythmics, i.e., myocardial sodium-, potassium-, and calcium-channels or beta-adrenergic receptors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10810787", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 1079, "text": "The sodium-channel blockade induced by class-I substances is enhanced with increasing heart rates. Thus, class-I antiarrhythmics can be subclassified as substances showing a more exponential, an approximately linear, or rather saturated block-frequency relation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10810787", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1270, "text": "Class-III antiarrhythmics (potassium-channel blockade) can be further differentiated according to the component of the delayed rectifier potassium current (IK) which is inhibited by a drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10810787", "endSection": "abstract" }, { "offsetInBeginSection": 1711, "offsetInEndSection": 1863, "text": "Class-III substances inhibiting the slowly activating IKs component are currently under investigation and are expected to show a direct rate dependence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10810787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9803978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV) according to defined electrophysiological effects on the myocardium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10810787", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 337, "text": "The classification of antiarrhythmic agents according to Vaughan Williams is based on electrophysiological findings in isolated heart muscle and defines four classes of drug actions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1290288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11564050", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 575, "text": "Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11564050", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 707, "text": "Class III antiarrhythmic agents include sotalol and amiodarone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11564050", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 920, "text": "Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11564050", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 819, "text": "These are classified according to their electrophysiological effects observed in isolated cardiac tissues in vitro (Vaughan Williams, 1989). Fast sodium channel blockers (class I) which reduce the upstroke velocity of the action potential are usually subclassified into three groups, class I A-C, according to their effect on the action potential duration. Beta-adrenergic antagonists (class II) exert their effects by antagonizing the electrophysiological effects of beta-adrenergic catecholamines. Class III antiarrhythmic agents (eg amiodarone) prolong the action potential and slow calcium channel blockers (class IV) suppress the calcium inward current and calcium-dependent action potentials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7875632", "endSection": "abstract" } ] }, { "body": "Which are the different isoforms of the mammalian Notch receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23028706", "http://www.ncbi.nlm.nih.gov/pubmed/21639801", "http://www.ncbi.nlm.nih.gov/pubmed/21356309", "http://www.ncbi.nlm.nih.gov/pubmed/22842086", "http://www.ncbi.nlm.nih.gov/pubmed/11532344", "http://www.ncbi.nlm.nih.gov/pubmed/11732008", "http://www.ncbi.nlm.nih.gov/pubmed/16307184" ], "ideal_answer": [ "Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Four Notch receptors have been identified in man: Notch-1, Notch-2, Notch-3 and Notch-4." ], "exact_answer": [ [ "Notch-1" ], [ "Notch-2" ], [ "Notch-3" ], [ "Notch-4" ] ], "type": "list", "id": "55072c803b8a5dc045000001", "snippets": [ { "offsetInBeginSection": 346, "offsetInEndSection": 597, "text": "Here, we investigate protein interactions between NOTCH3 and other vascular Notch isoforms and characterize the effects of elevated NOTCH3 on smooth muscle gene regulation. We demonstrate that NOTCH3 forms heterodimers with NOTCH1, NOTCH3, and NOTCH4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028706", "endSection": "abstract" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1388, "text": "We conclude that CADASIL mutants of NOTCH3 complex with NOTCH1, 3, and 4, slow NOTCH3 clearance, and that overexpressed wild type and mutant NOTCH3 protein interfere with key NOTCH-mediated functions in smooth muscle cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "In the vertebrate embryo, skeletal muscle is derived from the myotome of the somites. Notch1-3 demonstrate overlapping and distinct expression patterns in mouse somites. Notch1 and Notch2 have been shown to be inhibitors of skeletal myogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21356309", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 684, "text": "In this study, we analyzed the immunohistochemical staining pattern of four Notch receptors (Notch1-4) and their ligands (Delta1 and Jagged1) in 14 synovial tissues obtained from 14 RA patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16307184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Four Notch receptors have been identified in man (Notch-1 to -4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11732008", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 658, "text": "All 4 receptors were expressed in the adult liver, with no significant differences in the levels of Notch-1, -2, and -4 messenger RNA (mRNA) between normal and diseased liver. However, Notch-3 expression appeared to be increased in diseased tissue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11732008", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1142, "text": "We studied the immunohistochemical expression of NOTCH2 and its isoforms NOTCH1, NOTCH3, and NOTCH4 and the NOTCH2 primary ligand JAGGED1 in hepatoblastomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21639801", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 231, "text": "There are four different mammalian Notch receptors that can be activated by five cell surface ligands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22842086", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 304, "text": "There are four mammalian Notch receptors that have only partially overlapping functions despite sharing similar structures and ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11532344", "endSection": "abstract" } ] }, { "body": "Which are the major characteristics of cellular senescence?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9624027", "http://www.ncbi.nlm.nih.gov/pubmed/18976161", "http://www.ncbi.nlm.nih.gov/pubmed/8824885" ], "ideal_answer": [ "The defining characteristics of cellular senescence are altered morphology, arrested cell-cycle progression, development of aberrant gene expression with proinflammatory behavior, and telomere shortening." ], "exact_answer": [ [ "altered morphology" ], [ "arrested cell-cycle progression" ], [ "development of aberrant gene expression with proinflammatory behavior" ], [ "telomere shortening" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090398", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016922", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000772", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000773", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000774" ], "type": "list", "id": "53061af558348c0f52000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Cellular senescence is recognized as a critical cellular response to prolonged rounds of replication and environmental stresses. Its defining characteristics are arrested cell-cycle progression and the development of aberrant gene expression with proinflammatory behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18976161", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 368, "text": "telomeres are the central timing mechanism for cellular aging", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9624027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Recent research has shown that inserting a gene for the protein component of telomerase into senescent human cells reextends their telomeres to lengths typical of young cells, and the cells then display all the other identifiable characteristics of young, healthy cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9624027", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 655, "text": "Our data demonstrate that Sod1 transfected cell lines that have an elevation in the ratio of Sod1 activity to Gpx1 activity produce higher levels of H2O2 and exhibit well characterised markers of cellular senescence viz. slower proliferation and altered morphology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8824885", "endSection": "abstract" } ] }, { "body": "Orteronel was developed for treatment of which cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "http://www.ncbi.nlm.nih.gov/pubmed/24418642", "http://www.ncbi.nlm.nih.gov/pubmed/25537627", "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "http://www.ncbi.nlm.nih.gov/pubmed/25624429", "http://www.ncbi.nlm.nih.gov/pubmed/25264242", "http://www.ncbi.nlm.nih.gov/pubmed/21978946", "http://www.ncbi.nlm.nih.gov/pubmed/26150028", "http://www.ncbi.nlm.nih.gov/pubmed/24100689" ], "ideal_answer": [ "Orteronel was developed for treatment of castration-resistant prostate cancer." ], "exact_answer": [ "castration-resistant prostate cancer" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "factoid", "id": "56c1f01def6e394741000045", "snippets": [ { "offsetInBeginSection": 225, "offsetInEndSection": 395, "text": "Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26150028", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1087, "text": "The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26150028", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1879, "text": " Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P<0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P<0.00001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26150028", "endSection": "abstract" }, { "offsetInBeginSection": 2416, "offsetInEndSection": 2541, "text": "Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26150028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "BACKGROUND: Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "endSection": "abstract" }, { "offsetInBeginSection": 2578, "offsetInEndSection": 2793, "text": "NTERPRETATION: In chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus prednisone versus placebo plus prednisone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "endSection": "abstract" }, { "offsetInBeginSection": 2986, "offsetInEndSection": 3123, "text": "On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25624429", "endSection": "title" }, { "offsetInBeginSection": 111, "offsetInEndSection": 246, "text": "This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25624429", "endSection": "abstract" }, { "offsetInBeginSection": 1690, "offsetInEndSection": 1780, "text": "Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25624429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A phase 1 multiple-dose study of orteronel in Japanese patients with castration-resistant prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25537627", "endSection": "title" }, { "offsetInBeginSection": 97, "offsetInEndSection": 305, "text": "We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25537627", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1642, "text": "CONCLUSIONS: Orteronel at doses up to 400 mg BID was tolerable in Japanese CRPC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25537627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Orteronel for the treatment of prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Orteronel (also known as TAK-700) is a novel hormonal therapy that is currently in testing for the treatment of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25264242", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 1043, "text": "Early reports of clinical studies demonstrate that orteronel treatment leads to reduced prostate-specific antigen levels, a marker of prostate cancer tumor burden, and more complete suppression of androgen synthesis than conventional androgen deprivation therapies that act in the testes alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21978946", "endSection": "title" }, { "offsetInBeginSection": 790, "offsetInEndSection": 993, "text": "Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21978946", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 413, "text": "We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25264242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Phase I/II trial of orteronel (TAK-700)--an investigational 17,20-lyase inhibitor--in patients with metastatic castration-resistant prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24418642", "endSection": "title" }, { "offsetInBeginSection": 2986, "offsetInEndSection": 3232, "text": "On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer.FUNDING: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 1043, "text": "New androgen biosynthesis inhibitors have been developed, such as orteronel (TAK-700), but also new antiandrogens (enzalutamide, ARN-509, ODM-201) or even agents with a dual mechanism of action (galeterone). In this review the development of new hormonal therapies following the arrival of abiraterone for the treatment of prostate cancer will be summarized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24100689", "endSection": "abstract" } ] }, { "body": "Is the monoclonal antibody Trastuzumab (Herceptin) of potential use in the treatment of prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23294030", "http://www.ncbi.nlm.nih.gov/pubmed/10473102", "http://www.ncbi.nlm.nih.gov/pubmed/11786427", "http://www.ncbi.nlm.nih.gov/pubmed/17210707", "http://www.ncbi.nlm.nih.gov/pubmed/21364123", "http://www.ncbi.nlm.nih.gov/pubmed/12173324", "http://www.ncbi.nlm.nih.gov/pubmed/22322558", "http://www.ncbi.nlm.nih.gov/pubmed/16163160", "http://www.ncbi.nlm.nih.gov/pubmed/11236029", "http://www.ncbi.nlm.nih.gov/pubmed/10519379", "http://www.ncbi.nlm.nih.gov/pubmed/15919200", "http://www.ncbi.nlm.nih.gov/pubmed/20716957", "http://www.ncbi.nlm.nih.gov/pubmed/11502465", "http://www.ncbi.nlm.nih.gov/pubmed/15046685", "http://www.ncbi.nlm.nih.gov/pubmed/11685733", "http://www.ncbi.nlm.nih.gov/pubmed/17211467", "http://www.ncbi.nlm.nih.gov/pubmed/11920466", "http://www.ncbi.nlm.nih.gov/pubmed/17142577", "http://www.ncbi.nlm.nih.gov/pubmed/11685722", "http://www.ncbi.nlm.nih.gov/pubmed/21844010", "http://www.ncbi.nlm.nih.gov/pubmed/18038879", "http://www.ncbi.nlm.nih.gov/pubmed/21326934", "http://www.ncbi.nlm.nih.gov/pubmed/12677892", "http://www.ncbi.nlm.nih.gov/pubmed/15036648", "http://www.ncbi.nlm.nih.gov/pubmed/22977535", "http://www.ncbi.nlm.nih.gov/pubmed/23255921", "http://www.ncbi.nlm.nih.gov/pubmed/15264245", "http://www.ncbi.nlm.nih.gov/pubmed/15139054", "http://www.ncbi.nlm.nih.gov/pubmed/18071949", "http://www.ncbi.nlm.nih.gov/pubmed/19373278", "http://www.ncbi.nlm.nih.gov/pubmed/11331475", "http://www.ncbi.nlm.nih.gov/pubmed/22505344", "http://www.ncbi.nlm.nih.gov/pubmed/15571968", "http://www.ncbi.nlm.nih.gov/pubmed/21254978", "http://www.ncbi.nlm.nih.gov/pubmed/22137850" ], "ideal_answer": [ "Although is still controversial, Trastuzumab (Herceptin) can be of potential use in the treatment of prostate cancer overexpressing HER2, either alone or in combination with other drugs." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4002084", "http://www.disease-ontology.org/api/metadata/DOID:10283" ], "type": "yesno", "id": "5313b049e3eabad021000013", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 161, "text": "Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23294030", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1735, "text": "Our data demonstrate that Re-188-labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with androgen-independent prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23294030", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 194, "text": "epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extra-cellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23255921", "endSection": "abstract" }, { "offsetInBeginSection": 1644, "offsetInEndSection": 1843, "text": " there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23255921", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 1150, "text": "We performed a comparative analysis in vitro and in vivo of the antitumor effects of three different antibodies targeting different epitopes of ErbB2: Herceptin (trastuzumab), 2C4 (pertuzumab) and Erb-hcAb (human anti-ErbB2-compact antibody), a novel fully human compact antibody produced in our laboratory. Herein, we demonstrate that the growth of both androgen-dependent and independent prostate cancer cells was efficiently inhibited by Erb-hcAb. The antitumor effects induced by Erb-hcAb on some cell lines were more potent than those observed for either Herceptin or 2C4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505344", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1058, "text": "These findings suggest that a systemic delivery of 212Pb-trastuzumab could be an effective modality for management of advanced human prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22322558", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 149, "text": "Human epidermal growth factor receptor type 2 (HER2) overexpression supports proliferation of androgen-independent prostate cancer (PC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137850", "endSection": "abstract" }, { "offsetInBeginSection": 1722, "offsetInEndSection": 1861, "text": "Radiolabeled ABY-025 Affibody molecule provides higher contrast in imaging of HER2-expressing PC xenografts than radiolabeled trastuzumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137850", "endSection": "abstract" }, { "offsetInBeginSection": 1706, "offsetInEndSection": 1848, "text": "These studies indicate that dual EGFR/HER2 inhibition, administered together with AWT, sensitize prostate cancer cells to apoptosis during AWT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21844010", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 508, "text": "The overall goal of these studies is to determine whether dual inhibition of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER2 would prolong the effectiveness of this treatment in prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21844010", "endSection": "abstract" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1107, "text": "The expression of HER2 was demonstrated and quantified in all three tested prostate cancer cell-lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22977535", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1523, "text": "Such features would definitely favor the use of radiometal labels for trastuzumab and, most likely, for affibody molecules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22977535", "endSection": "abstract" }, { "offsetInBeginSection": 1579, "offsetInEndSection": 1848, "text": "our data demonstrate that Her2 plays an important role in the support of AR protein stability in the transition of androgen requirement in prostate cancer cells. We hope these findings will provide novel insight into the treatment of hormone-refractory prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364123", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1429, "text": "These two cell lines exhibited distinct responses to Her2 activation (by heregulin treatment) on Her2 phosphorylation and Her2 inhibition (by AG825 or Herceptin treatments) on proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364123", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 457, "text": " While prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by lentiviruses with envelope proteins engineered to bind to this therapeutic antibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21326934", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 517, "text": "Overexpression of ErbB-2 and EGFR has been associated with aggressive disease and poor patient prognosis in a range of human tumour types (e.g. breast, lung, ovarian, prostate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21254978", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 796, "text": "Various approaches have been developed to target the ErbB signalling pathways including monoclonal antibodies (trastuzumab/Herceptin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21254978", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1555, "text": "The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20716957", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 534, "text": "Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian, and prostate carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20716957", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1397, "text": "we found that although prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by viruses with envelope proteins engineered to bind this antibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19373278", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 177, "text": "detection of prostate cancer (PCa) and advances in hormonal and chemotherapy treatments have provided great clinical benefits to patients with early stages of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18071949", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1182, "text": "MAbs directed to established targets include those approved for other solid tumors, including anti-human epidermal growth factor receptor-2 (HER2) MAb trastuzumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18071949", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1431, "text": "We conclude that Her2/neu expression in the peripheral blood mononuclear cell fraction of prostate cancer patients is frequent and therefore this assay may potentially be useful to detect the presence of micrometastatic disease in men with prostate cancer and for monitoring patients enrolled in trastuzumab-based therapeutic protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18038879", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1552, "text": "This study suggests that the docetaxel/trastuzumab combination may prove an effective therapeutic approach for HER2-expressing hormone-refractory prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17211467", "endSection": "abstract" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1629, "text": "there was no significant difference in antimetastatic activity between the emulsion and the immunoemulsion despite the affinity of the immunoemulsion towards the HER2 receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17210707", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 896, "text": "a targeted drug delivery system based on cationic emulsion covalently linked to anti-HER2 monoclonal antibody (Herceptin), in a well-established in vivo pharmacologic model of metastatic prostate cancer that overexpresses the HER2 receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17210707", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1198, "text": "The finding of strong, consistent HER-2/neu expression in ACBCC suggests that treatment with Herceptin (trastuzumab) may be effective in patients with this rare tumour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17142577", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 807, "text": "Although HER2 can be over-expressed in prostate cancer, there is no clinical data to support the use of trastuzumab for prostate cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16163160", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1066, "text": "whereas the effect of the trastuzumab-RT combination was inferior to that predicted by the individual effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15919200", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 86, "text": "HER 1-2 targeting of hormone-refractory prostate cancer by ZD1839 and trastuzumab", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15571968", "endSection": "title" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1048, "text": "Trastuzumab (Herceptin) as a single agent demonstrated poor efficacy in treating HRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15264245", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 187, "text": "To investigate the efficacy and toxicity of the antibody to the HER-2/neu receptor (trastuzumab, Herceptin) in the treatment of advanced hormone-refractory prostate cancer (HRPC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15264245", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1679, "text": "Conclusions regarding the predictive value of HER-2 status on outcome after trastuzumab-based therapy were not reached and were only drawn after larger-scale screening efforts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15139054", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 67, "text": "rastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15139054", "endSection": "title" }, { "offsetInBeginSection": 1869, "offsetInEndSection": 2034, "text": "clinical trials are currently in progress in patients with prostate cancer testing novel agents that selectively interfere with these receptors, such as trastuzumab,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15046685", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 122, "text": "ytotoxicity of human prostate cancer cell lines in vitro and induction of apoptosis using 213Bi-Herceptin alpha-conjugate", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15036648", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 561, "text": "The clinical interpretation of c-erbB-2 abnormalities should reflect the complexity of c-erbB-2 mediated regulatory pathway and explain why tumours with overexpression/amplification of c-erbB-2 very often do not respond to therapy using Herceptin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12677892", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 295, "text": "HER-2 overexpression also has been reported in up to 60% of patients with hormone-refractory prostate carcinoma (HRPC) and was correlated with shortened survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12173324", "endSection": "abstract" }, { "offsetInBeginSection": 2235, "offsetInEndSection": 2574, "text": "Unlike breast carcinoma and contrary to prior reports, HER-2 overexpression by IHC in archival prostate tissue from patients who eventually developed hormone-refractory disease was infrequent. There did not appear to be any correlation between HER-2 overexpression by IHC and shed HER-2 antigen levels in serum by ELISA in this tumor type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12173324", "endSection": "abstract" }, { "offsetInBeginSection": 2019, "offsetInEndSection": 2270, "text": "Further development of trastuzumab for the treatment of patients with metastatic prostate carcinoma is not feasible until more reliable and practical methods of sampling metastatic disease are developed to identify patients with HER-2 positive tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11920466", "endSection": "abstract" }, { "offsetInBeginSection": 1549, "offsetInEndSection": 1792, "text": "the expression of ERBB2 in prostate cancer is relatively low, and is not altered during disease progression. Thus, it is unlikely that treatment modalities relying on the overexpression of ERBB2 gene will be useful in treating prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11786427", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 392, "text": "A phase I study was designed to evaluate docetaxel/estramustine plus trastuzumab, a humanized monoclonal antibody that binds to the HER2 receptor, in patients with metastatic androgen-independent prostate cancer (AIPC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11685733", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1170, "text": "Laboratory evidence also supports the clinical evaluation of docetaxel-based combinations that include agents such as trastuzumab and/or estramustine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11685722", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 702, "text": "trastuzumab, a monoclonal antibody binding to the HER2 receptor; immunotoxin conjugates use an antibody directed against EGFR joined to a cell toxin. All are in clinical trials for a number of cancers, including prostate cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11502465", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 366, "text": "we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11331475", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 480, "text": "trastuzumab was found to have additive and synergistic effects with some chemotherapeutic agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11236029", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 80, "text": "ER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11236029", "endSection": "title" }, { "offsetInBeginSection": 1683, "offsetInEndSection": 1844, "text": "in these prostate cancer model systems, Herceptin alone has clinical activity only in the androgen-dependent tumor and has at least an additive effect on growth,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10519379", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1446, "text": "anti-HER2 receptor monoclonal antibody Herceptin significantly enhanced growth inhibition of the MDA PCa 2a cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473102", "endSection": "abstract" } ] }, { "body": "Which are the Yamanaka factors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21761058", "http://www.ncbi.nlm.nih.gov/pubmed/21839145", "http://www.ncbi.nlm.nih.gov/pubmed/23612755", "http://www.ncbi.nlm.nih.gov/pubmed/23939864", "http://www.ncbi.nlm.nih.gov/pubmed/24150221", "http://www.ncbi.nlm.nih.gov/pubmed/22357549", "http://www.ncbi.nlm.nih.gov/pubmed/19030024", "http://www.ncbi.nlm.nih.gov/pubmed/23527808", "http://www.ncbi.nlm.nih.gov/pubmed/23658991", "http://www.ncbi.nlm.nih.gov/pubmed/21640101", "http://www.ncbi.nlm.nih.gov/pubmed/20144262", "http://www.ncbi.nlm.nih.gov/pubmed/23704989", "http://www.ncbi.nlm.nih.gov/pubmed/22449255", "http://www.ncbi.nlm.nih.gov/pubmed/22075965", "http://www.ncbi.nlm.nih.gov/pubmed/21249204", "http://www.ncbi.nlm.nih.gov/pubmed/23166588" ], "ideal_answer": [ "The Yamanaka factors are the OCT4, SOX2, MYC, and KLF4 transcription factors" ], "exact_answer": [ [ "OCT4", "Oct3/4", "Pou5f1" ], [ "SOX2" ], [ "MYC", "c-MYC" ], [ "KLF4" ] ], "type": "list", "id": "53137541e3eabad021000010", "snippets": [ { "offsetInBeginSection": 462, "offsetInEndSection": 505, "text": "Yamanaka factors (OCT4, SOX2, MYC, and KLF4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704989", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 63, "text": "Yamanaka factors' (Oct4, Sox2, Klf4 and c-Myc)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24150221", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 350, "text": "Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23939864", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 862, "text": "Yamanaka factors (c-myc, KLF4, Oct3/4 and SOX2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23612755", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 877, "text": "Yamanaka factors (i.e., Oct4, Sox2, Klf4, and c-Myc) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658991", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 160, "text": "Yamanaka factors (Oct3/4, Sox2, Klf4, and c-Myc)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527808", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 886, "text": "Yamanaka factors (OCT4, SOX2, KLF4, cMYC - OSKM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166588", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 726, "text": "Oct4, Sox2, Klf4 and cMyc (4TF, Yamanaka factors) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22449255", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 854, "text": "Yamanaka factors (Pou5f1, Myc, Klf4, and Sox2) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357549", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 611, "text": "c-Myc, Klf4, Oct3/4, and Sox2 (the so-called \"Yamanaka factors\")", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075965", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1049, "text": "Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839145", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 275, "text": "Yamanaka factors, namely Sox2, Oct3/4 (Pou5f1), Klf4, and c-Myc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761058", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 218, "text": "Oct4, Sox2, Klf4 and c-Myc, also known as the Yamanaka factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21640101", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 715, "text": "Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249204", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 810, "text": "Yamanaka factors Oct4, Sox2, Klf4, and c-Myc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20144262", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 44, "text": "amanaka factors (Oct3/4, Sox2, Klf4, c-Myc)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19030024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19030024", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 337, "text": "These protein sets have been called the Yamanaka factors, namely Sox2, Oct3/4 (Pou5f1), Klf4, and c-Myc, and the Thomson factors, namely Sox2, Oct3, Lin28, and Nanog", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19030024", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 756, "text": "Transcription factors, Oct4, Sox2, Klf4 and cMyc (4TF, Yamanaka factors) are used as basal conditions to generate iPS cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22449255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Generation of induced pluripotent stem (iPS) cells from somatic cells has been successfully achieved by ectopic expression of four transcription factors, Oct4, Sox2, Klf4 and c-Myc, also known as the Yamanaka factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21640101", "endSection": "abstract" } ] }, { "body": "What is the aim of the Human Chromosome-centric Proteome Project (C-HPP)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23312004", "http://www.ncbi.nlm.nih.gov/pubmed/23253012", "http://www.ncbi.nlm.nih.gov/pubmed/23252913", "http://www.ncbi.nlm.nih.gov/pubmed/22966780", "http://www.ncbi.nlm.nih.gov/pubmed/23227862", "http://www.ncbi.nlm.nih.gov/pubmed/23259496", "http://www.ncbi.nlm.nih.gov/pubmed/21742803", "http://www.ncbi.nlm.nih.gov/pubmed/23205526", "http://www.ncbi.nlm.nih.gov/pubmed/23234512", "http://www.ncbi.nlm.nih.gov/pubmed/23308364", "http://www.ncbi.nlm.nih.gov/pubmed/23214983", "http://www.ncbi.nlm.nih.gov/pubmed/23276153", "http://www.ncbi.nlm.nih.gov/pubmed/23153008", "http://www.ncbi.nlm.nih.gov/pubmed/23249167", "http://www.ncbi.nlm.nih.gov/pubmed/22443261" ], "ideal_answer": [ "The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams", "The Chromosome-Centric Human Proteome Project (C-HPP) is an international effort for creating an annotated proteomic catalog for each chromosome. (PMID: 23312004) The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams. (PMID: 23308364) The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. (PMID: 23253012)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002875", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D041322", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002877" ], "type": "summary", "id": "515aa0abd24251bc050000a8", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The Chromosome-Centric Human Proteome Project (C-HPP) is an international effort for creating an annotated proteomic catalog for each chromosome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312004", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23308364", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23276153", "endSection": "sections.0" }, { "offsetInBeginSection": 317, "offsetInEndSection": 423, "text": "dedicated to a systematic description of proteins as gene products encoded in the human genome (the C-HPP)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259496", "endSection": "sections.0" }, { "offsetInBeginSection": 856, "offsetInEndSection": 915, "text": "a chromosome-centric protein mapping strategy, termed C-HPP", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742803", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23253012", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 669, "text": "The objective of the international Chromosome-Centric Human Proteome Project (C-HPP) is to map and annotate all proteins encoded by the genes on each human chromosome. The C-HPP consortium was established to organize a collaborative network among the research teams responsible for protein mapping of individual chromosomes and to identify compelling biological and genetic mechanisms influencing colocated genes and their protein products. The C-HPP aims to foster the development of proteome analysis and integration of the findings from related molecular -omics technology platforms through collaborations among universities, industries, and private research groups.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22443261", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "The goal of the Human Proteome Project (HPP) is to fully characterize the 21,000 human protein-coding genes with respect to the estimated two million proteins they encode. As such, the HPP aims to create a comprehensive, detailed resource to help elucidate protein functions and to advance medical treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22966780", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The Chromosome-centric Human Proteome Project (C-HPP) aims to define all proteins encoded in each chromosome and especially to identify proteins that currently lack evidence by mass spectrometry.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153008", "endSection": "sections.0" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1115, "text": "Our results will contribute to the accomplishment of the primary goal of the C-HPP in identifying so-called \"missing proteins\" and generating a whole protein catalog for each chromosome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153008", "endSection": "sections.0" }, { "offsetInBeginSection": 138, "offsetInEndSection": 398, "text": "there is only little information relative to their abundance, distribution, subcellular localization, interactions, or cellular functions. The aim of the HUPO Human Proteome Project (HPP, www.thehpp.org ) is to collect this information for every human protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23205526", "endSection": "sections.0" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1042, "text": ". To support the efforts of the Chromosome-centric Human Proteome Project Consortium, we have annotated these proteins with their respective chromosome location.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23214983", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "One of the major challenges of a chromosome-centric proteome project is to explore in a systematic manner the potential proteins identified from the chromosomal genome sequence, but not yet characterized on a protein level.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227862", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "The Chromosome 16 Consortium forms part of the Human Proteome Project that aims to develop an entire map of the proteins encoded by the human genome following a chromosome-centric strategy (C-HPP) to make progress in the understanding of human biology in health and disease (B/D-HPP).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23234512", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented ( http://www.c-hpp.org ).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23249167", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "In an effort to map the human proteome, the Chromosome-centric Human Proteome Project (C-HPP) was recently initiated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23252913", "endSection": "sections.0" } ] }, { "body": "Where is the protein Pannexin1 located?", "documents": [ 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"http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17400569", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2743999", "o": "http://linkedlifedata.com/resource/umls/id/C0969748" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17909603", "o": "Brachydanio rerio Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17885251", "o": "Zebra Danio Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2030874", "o": "Danio rerio Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18005491", "o": "Zebrafish Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17885252", "o": "Zebrafish Proteins [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17909604", "o": "Zebra Fish Proteins" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0969748", "o": "http://linkedlifedata.com/resource/umls/id/C2743999" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2743999", "o": "http://linkedlifedata.com/resource/umls/id/C0110611" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18025970", "o": "Connexins [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0361672", "o": "Gap Junction Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15367648", "o": "Connexin" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17882031", "o": "Protein, Gap Junction" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1305072", "o": "connexin" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0188058", "o": "Gap Junction Protein" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18025971", "o": "Proteins, Gap Junction" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0361674", "o": "Junction Protein, Gap" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0361675", "o": "Junction Proteins, Gap" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12992664", "o": "Gap Junction Channel Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A4365650", "o": "Connexins" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0110611", "o": "http://linkedlifedata.com/resource/umls/id/C2743999" }, { "p": "http://www.w3.org/2004/02/skos/core#inScheme", "s": "http://linkedlifedata.com/resource/umls/id/C2743999", "o": "http://linkedlifedata.com/resource/umls" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q29ZM8", "o": "http://linkedlifedata.com/resource/#_5132395A4D38008" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5132395A4D38008", "o": "Pannexin1" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R120084487", "o": "http://linkedlifedata.com/resource/umls/id/C2743999" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C2743999", "o": "http://linkedlifedata.com/resource/umls/relation/R119818176" } ], "ideal_answer": [ "The protein Pannexin1 is localized to the plasma membranes." ], "exact_answer": [ "plasma membrane" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051179" ], "type": "factoid", "id": "56af9f130a360a5e45000015", "snippets": [ { "offsetInBeginSection": 394, "offsetInEndSection": 620, "text": "zfPanx1 was identified on the surface of horizontal cell dendrites invaginating deeply into the cone pedicle near the glutamate release sites of the cones, providing in vivo evidence for hemichannel formation at that location.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19409451", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 915, "text": "pannexin1, a vertebrate homolog of invertebrate gap junction proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17064878", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 422, "text": "The specific profile of gap junction proteins, the connexins, expressed in these different cell types forms compartments of intercellular communication that can be further shaped by the release of extracellular nucleotides via pannexin1 channels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26100513", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 430, "text": "Recent studies demonstrated that ATP can be released from cells in a controlled manner through pannexin (Panx) channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24642372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "The ATP release channel Pannexin1 (Panx1) is self-regulated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24694658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The membrane protein Pannexin1 forms two open-channel conformations depending on the mode of activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25056878", "endSection": "title" }, { "offsetInBeginSection": 92, "offsetInEndSection": 143, "text": " Pannexin1 channels traffic to the plasma membrane.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25698922", "endSection": "title" }, { "offsetInBeginSection": 204, "offsetInEndSection": 340, "text": "We previously showed that pannexins form oligomeric channels but unlike connexins and innexins, they form only single membrane channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25698922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 30, "text": "ATP release channel Pannexin1 ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25007779", "endSection": "title" }, { "offsetInBeginSection": 209, "offsetInEndSection": 359, "text": "Pannexin1 (Panx1) is a newly discovered extracellular ATP release channel with a wide tissue distribution and diverse biological functions in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25007779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "In mammals, a single pannexin1 gene (Panx1) is widely expressed in the CNS including the inner and outer retinae, forming large-pore voltage-gated membrane channels, which are involved in calcium and ATP signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194896", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 366, "text": "Six of them form a \"gap junction hemichannel-like\" structure that connects the cytoplasm with the extracellular space; here they will be called Panx1 channels. These are poorly selective channels permeable to ions, small metabolic substrate, and signaling molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24782784", "endSection": "abstract" } ] }, { "body": "Which currently known mitochondrial diseases have been attributed to POLG mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20927567", "http://www.ncbi.nlm.nih.gov/pubmed/12825077", "http://www.ncbi.nlm.nih.gov/pubmed/18546365", "http://www.ncbi.nlm.nih.gov/pubmed/22647225", "http://www.ncbi.nlm.nih.gov/pubmed/15351195" ], "ideal_answer": [ "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO).", "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO)" ], "exact_answer": [ [ "childhood Myocerebrohepatopathy Spectrum disorders (MCHS)" ], [ "Alpers syndrome" ], [ "Ataxia Neuropathy Spectrum (ANS) disorders" ], [ "Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA)" ], [ "autosomal recessive Progressive External Ophthalmoplegia (arPEO)" ], [ "autosomal dominant Progressive External Ophthalmoplegia (adPEO)" ] ], "type": "list", "id": "5718bbb37de986d80d00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 576, "text": "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18546365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Mutations in the gene encoding mitochondrial DNA polymerase gamma (POLG), the enzyme that synthesises mitochondrial DNA (mtDNA), have been associated with a mitochondrial disease-autosomal dominant or recessive progressive external ophthalmoplegia-and multiple deletions of mtDNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15351195", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 486, "text": "About 150 mutations in the human POLG have been identified in patients with mitochondrial diseases such as Alpers syndrome, progressive external ophthalmoplegia, and ataxia-neuropathy syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20927567", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 1030, "text": "Nineteen exhibited a cluster of three or more predefined clinical manifestations suggestive of POLG-related disease: progressive external ophthalmoplegia, seizures and/or an abnormal electroencephalogram, neuropathy, ataxia, liver function abnormalities, migraine or dysphagia/dysarthria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647225", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12825077", "endSection": "title" } ] }, { "body": "What is the effect of ivabradine in heart failure after myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21838751", "http://www.ncbi.nlm.nih.gov/pubmed/19074674", "http://www.ncbi.nlm.nih.gov/pubmed/14981003", "http://www.ncbi.nlm.nih.gov/pubmed/19411283", "http://www.ncbi.nlm.nih.gov/pubmed/18757088", "http://www.ncbi.nlm.nih.gov/pubmed/19129742", "http://www.ncbi.nlm.nih.gov/pubmed/20000882", "http://www.ncbi.nlm.nih.gov/pubmed/19664404", "http://www.ncbi.nlm.nih.gov/pubmed/18310678", "http://www.ncbi.nlm.nih.gov/pubmed/23096376", "http://www.ncbi.nlm.nih.gov/pubmed/21878041", "http://www.ncbi.nlm.nih.gov/pubmed/22416440", "http://www.ncbi.nlm.nih.gov/pubmed/19514618", "http://www.ncbi.nlm.nih.gov/pubmed/23536611", "http://www.ncbi.nlm.nih.gov/pubmed/18621770", "http://www.ncbi.nlm.nih.gov/pubmed/23067195", "http://www.ncbi.nlm.nih.gov/pubmed/20028694", "http://www.ncbi.nlm.nih.gov/pubmed/23394554" ], "ideal_answer": [ "\u0399vabradine decreases heart rate and reduces myocardial oxygen demand, increases diastolic perfusion time and improves energetics in ischemic myocardium. Ivabradine protects the myocardium during ischemia, improves left ventricular function in heart failure and reduces remodeling following myocardial infarction. It improves prognosis in patients with coronary artery disease, left ventricular dysfunction and heart rate \u226570 beats per minute, as well as in patients with heart failure and left ventricular dysfunction. The beneficial effects of ivabradine may be due to the reversal of electrophysiological cardiac remodelling in post-MI rats by reduction of functional overexpression of HCN channels. Furthermore, the improvement of cardiac function is related not only to the HR reduction per se but also to modifications in the extracellular matrix." ], "concepts": [ "http://www.biosemantics.org/jochem#4266225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143" ], "type": "summary", "id": "532f062ad6d3ac6a34000027", "snippets": [ { "offsetInBeginSection": 1290, "offsetInEndSection": 1515, "text": "Ivabradine may be important for the improvement of clinical outcomes in patients with LV systolic dysfunction and heart rate \u2265 70 b.p.m., whatever the primary clinical presentation (CAD or HF) or clinical status (NYHA class).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23536611", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 888, "text": "Treatment with ivabradine was associated with a 13% relative risk reduction for the composite of cardiovascular mortality or HF hospitalization (P < 0.001 vs. placebo); this was driven by HF hospitalizations (19%, P < 0.001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23536611", "endSection": "abstract" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1766, "text": "Ivabradine (IVA), a pure HR lowering drug, reduces the demand of myocardial oxygen during exercise, contributes to the restoration of oxygen balance and is therefore beneficial in chronic CVD. No relevant negative effects have been observed on cardiac conduction, contractility, relaxation, repolarization or blood pressure (BP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394554", "endSection": "abstract" }, { "offsetInBeginSection": 2149, "offsetInEndSection": 2651, "text": "The most significant results were obtained in the subgroup of patients with life-limiting exertional angina. In this group, ivabradine significantly reduced the primary endpoint, a composite of cardiovascular death, hospitalization for fatal and nonfatal acute myocardial infarction (AMI) or heart failure, by 24%, and hospitalizations for AMI by 42%. In the subgroup of patients with baseline heart rate >70 bpm, hospitalizations for AMI and revascularization were reduced by 73% and 59%, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23096376", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 975, "text": "Indeed, heart rate reduction with ivabradine, a selective and specific I(f) inhibitor, reduces myocardial oxygen demand, increases diastolic perfusion time and improves energetics in ischemic myocardium. Ivabradine protects the myocardium during ischemia, improves left ventricular function in heart failure and reduces remodeling following myocardial infarction. It improves prognosis in patients with coronary artery disease, left ventricular dysfunction and heart rate \u226570 beats per minute, as well as in patients with heart failure and left ventricular dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21878041", "endSection": "abstract" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1790, "text": "The beneficial effects of ivabradine may be due to the reversal of electrophysiological cardiac remodelling in post-MI rats by reduction of functional overexpression of HCN channels. This is attributable to transcriptional and post-transcriptional mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838751", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1758, "text": "Addition of ivabradin to standard treatment of SCCF after MI promoted less frequency of hospitalizations, recurrent non-fatal MI, fatal cardiovascular events. This effect was especially strong in high baseline HR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22416440", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1447, "text": "The most important finding of the study was that patients with high baseline HR had an increase in serious cardiovascular events including death (34%), hospital admission secondary to congestive heart failure (53%), acute myocardial infarction (46%), or revascularization procedure (38%). In addition, in the subset analysis focusing on patients with baseline HR > or =70 bpm and left ventricular ejection fraction <40% the agent resulted in a 36% decrease in hospital admissions secondary to fatal and nonfatal myocardial infarction and a 30% decrease in coronary revascularization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20000882", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 1078, "text": "In the subgroup of patients with a baseline heart rate > or =70 bpm, treatment with ivabradine resulted in a significant, 36% reduction in the risk of myocardial infarction and a 20% reduction in the need for coronary revascularisation. Ivabradine was well tolerated, with an increased rate of treatment discontinuation, mainly due to bradycardia, compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19664404", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1289, "text": "Ivabradine did not significantly affect the combined primary endpoint. Significant reduction by 36% (p = 0.001) in myocardial infarction and by 30% (p = 0.016) in coronary revascularization was observed in the pre-defined subgroup of patients with heart rate > or = 70/min. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19514618", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1677, "text": "In conclusion, these data indicated that HR reduction by Iva prevents the worsening of LV dysfunction and remodeling that may be related to a downregulation of cardiac renin-angiotensin-aldosterone system transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074674", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1342, "text": "Interstitial fibrosis in the MI-remote LV was markedly reduced by Iva (4.0 +/- 0.1 vs. 1.8 +/- 0.1%, P < 0.005). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074674", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1729, "text": "Although both metoprolol and ivabradine comparably prevented post-MI deterioration of haemodynamic function in the rat, metoprolol had additional potentially beneficial effects; it prevented LV dilation and hypertrophy, chronotropic incompetence, strongly increased contractility of isolated cardiomyocytes, and prevented the potentially proarrhythmic increase in NCX activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18310678", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1779, "text": "In rats with CHF, long-term HRR induced by the selective I(f) inhibitor ivabradine improves LV function and increases stroke volume, preserving cardiac output despite the HRR. The improvement of cardiac function is related not only to the HRR per se but also to modifications in the extracellular matrix and/or function of myocytes as a consequence of long-term HRR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14981003", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of Wilson's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/838566", "http://www.ncbi.nlm.nih.gov/pubmed/12152840", "http://www.ncbi.nlm.nih.gov/pubmed/14580665", "http://www.ncbi.nlm.nih.gov/pubmed/20662462", "http://www.ncbi.nlm.nih.gov/pubmed/16932613", "http://www.ncbi.nlm.nih.gov/pubmed/1248830", "http://www.ncbi.nlm.nih.gov/pubmed/22610954", "http://www.ncbi.nlm.nih.gov/pubmed/2724779", "http://www.ncbi.nlm.nih.gov/pubmed/8615372", "http://www.ncbi.nlm.nih.gov/pubmed/1940586", "http://www.ncbi.nlm.nih.gov/pubmed/6620327", "http://www.ncbi.nlm.nih.gov/pubmed/8186659", "http://www.ncbi.nlm.nih.gov/pubmed/759736", "http://www.ncbi.nlm.nih.gov/pubmed/6109943" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4181", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1198" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1198", "o": "Wilson_disease" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1198", "o": "http://www.dbpedia.org/resource/Wilson%27s_disease" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4181", "o": "Wilson disease, 277900" } ], "ideal_answer": [ "Wilson's disease (WD) is an autosomal recessive disorder." ], "exact_answer": [ "autosomal recessive" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.disease-ontology.org/api/metadata/DOID:893", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006527", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020739", "http://www.disease-ontology.org/api/metadata/DOID:2214" ], "type": "factoid", "id": "52bf1b0a03868f1b06000009", "snippets": [ { "offsetInBeginSection": 122, "offsetInEndSection": 272, "text": "The disease has an autosomal recessive mode of inheritance, and is characterized by excessive copper deposition, predominantly in the liver and brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16932613", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 219, "text": " The inheritance is autosomal recessive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20662462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal recessive inheritance disorder of copper metabolism caused by ATP7B gene mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22610954", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 193, "text": "Inheritance seems most likely to be autosomal recessive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14580665", "endSection": "abstract" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1349, "text": "When familial, it is inherited recessively and has been linked to chromosome 20. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14580665", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 409, "text": "Inheritance of a pair of alleles of an autosomal recessive gene on chromosome 13 is necessary and sufficient to cause such copper accumulation in WD; reducing the dietary intake of copper cannot prevent the development of WD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8615372", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 177, "text": "Wilson's disease is a treatable movement disorder with autosomal recessive inheritance which is associated with severe morbidity and mortality if not treated early. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12152840", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 388, "text": "The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8186659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Wilson's disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1940586", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 305, "text": "Autosomal recessive inheritance indicates that siblings of affected patients are at 25% risk of having the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1940586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Wilson's disease is a rare genetic disorder of copper metabolism with autosomal recessive inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2724779", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1040, "text": "Recessive inheritance is, however, supported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6620327", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 338, "text": "The autosomal recessive mode of inheritance strongly suggests that mutation of a single gene causes the impairment of both caeruloplasmin synthesis and biliary copper excretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6109943", "endSection": "abstract" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1260, "text": "This is consistent with the autosomal-recessive pattern of inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/759736", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 408, "text": "The overall sex ratio of patients was nearly 1:1, and genetic analysis of 20 families confirmed an autosomal recessive mode of inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/838566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Dermatoglyphics of 11 patients with Wilson's disease and 16 of their clinically asymptomatic relatives of first degree were investigated; 11 of the latter ones were heterozygous in agreement with the turn over rates of Cu-67, 12 under the assumption of autosomal recessive inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1248830", "endSection": "abstract" } ] }, { "body": "Are transcription and splicing connected?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20808788", "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "http://www.ncbi.nlm.nih.gov/pubmed/23097425", "http://www.ncbi.nlm.nih.gov/pubmed/17189193", "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "http://www.ncbi.nlm.nih.gov/pubmed/16921380", "http://www.ncbi.nlm.nih.gov/pubmed/15870275", "http://www.ncbi.nlm.nih.gov/pubmed/22479188", "http://www.ncbi.nlm.nih.gov/pubmed/15383674", "http://www.ncbi.nlm.nih.gov/pubmed/15905409", "http://www.ncbi.nlm.nih.gov/pubmed/21095588", "http://www.ncbi.nlm.nih.gov/pubmed/16172632", "http://www.ncbi.nlm.nih.gov/pubmed/22975042", "http://www.ncbi.nlm.nih.gov/pubmed/22156210", "http://www.ncbi.nlm.nih.gov/pubmed/23209445", "http://www.ncbi.nlm.nih.gov/pubmed/16769980" ], "ideal_answer": [ "Yes. There is strong evidence that splicing and transcription are intimately coupled in metazoans, with genome wide surveys show that most splicing occurs during transcription. Chromatin structure, RNA polymerase dynamics, and recruitment of splicing factors through the transcriptional machinery are factors that explain a role for transcription in the regulation of splicing." ], "exact_answer": "yes", "type": "yesno", "id": "517395b98ed59a060a00001a", "snippets": [ { "offsetInBeginSection": 476, "offsetInEndSection": 791, "text": ", as splicing is often cotranscriptional, a complex picture emerges in which splicing regulation not only depends on the balance of splicing factor binding to their pre-mRNA target sites but also on transcription-associated features such as protein recruitment to the transcribing machinery and elongation kinetics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "endSection": "sections.0" }, { "offsetInBeginSection": 851, "offsetInEndSection": 968, "text": "recent evidence shows that chromatin structure is another layer of regulation that may act through various mechanisms", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "endSection": "sections.0" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1135, "text": "hese span from regulation of RNA polymerase II elongation, which ultimately determines splicing decisions, to splicing factor recruitment by specific histone marks.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "endSection": "sections.0" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1250, "text": "Chromatin may not only be involved in alternative splicing regulation but in constitutive exon recognition as well", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "endSection": "sections.0" }, { "offsetInBeginSection": 1252, "offsetInEndSection": 1480, "text": "Moreover, splicing was found to be necessary for the proper 'writing' of particular chromatin signatures, giving further mechanistic support to functional interconnections between splicing, transcription and chromatin structure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "endSection": "sections.0" }, { "offsetInBeginSection": 1481, "offsetInEndSection": 1671, "text": "These links between chromatin configuration and splicing raise the intriguing possibility of the existence of a memory for splicing patterns to be inherited through epigenetic modifications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "endSection": "sections.0" }, { "offsetInBeginSection": 148, "offsetInEndSection": 285, "text": "Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may directly influence alternative splicing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "endSection": "sections.0" }, { "offsetInBeginSection": 287, "offsetInEndSection": 475, "text": "upporting such an association, recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "endSection": "sections.0" }, { "offsetInBeginSection": 477, "offsetInEndSection": 564, "text": "Moreover, the rate of transcription elongation has been linked to alternative splicing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "endSection": "sections.0" }, { "offsetInBeginSection": 566, "offsetInEndSection": 827, "text": "ere we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wide", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "endSection": "sections.0" }, { "offsetInBeginSection": 148, "offsetInEndSection": 232, "text": "We recently showed that cotranscriptional splicing occurs efficiently in Drosophila,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23097425", "endSection": "sections.0" }, { "offsetInBeginSection": 138, "offsetInEndSection": 221, "text": "In recent years it became apparent that splicing is predominantly cotranscriptional", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975042", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 385, "text": "To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slowly, with \u223c3% being almost completely retained in nascent pre-mRNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22156210", "endSection": "sections.0" }, { "offsetInBeginSection": 720, "offsetInEndSection": 877, "text": "We estimate that > or =90% of endogenous yeast splicing is posttranscriptional, consistent with an analysis of posttranscriptional snRNP-associated pre-mRNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17189193", "endSection": "sections.0" }, { "offsetInBeginSection": 748, "offsetInEndSection": 1039, "text": "Notably, the topoisomerase I inhibitor camptothecin, which stalls elongating Pol II, increased cotranscriptional splicing factor accumulation and splicing in parallel. This provides direct evidence for a kinetic link between transcription, splicing factor recruitment and splicing catalysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16921380", "endSection": "sections.0" }, { "offsetInBeginSection": 739, "offsetInEndSection": 950, "text": "Recent evidence indicates that transcriptional elongation and splicing can be influenced reciprocally: Elongation rates control alternative splicing and splicing factors can, in turn, modulate pol II elongation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15383674", "endSection": "sections.0" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1251, "text": "The presence of transcription factors in the spliceosome and the existence of proteins, such as the coactivator PGC-1, with dual activities in splicing and transcription can explain the links between both processes and add a new level of complexity to the regulation of gene expression in eukaryotes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15383674", "endSection": "sections.0" } ] }, { "body": "What is the mode of inheritance of Facioscapulohumeral muscular dystrophy (FSHD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10864616", "http://www.ncbi.nlm.nih.gov/pubmed/15307599", "http://www.ncbi.nlm.nih.gov/pubmed/10969520", "http://www.ncbi.nlm.nih.gov/pubmed/19248726", "http://www.ncbi.nlm.nih.gov/pubmed/10487912", "http://www.ncbi.nlm.nih.gov/pubmed/23143600", "http://www.ncbi.nlm.nih.gov/pubmed/22551571", "http://www.ncbi.nlm.nih.gov/pubmed/7739631", "http://www.ncbi.nlm.nih.gov/pubmed/22525183", "http://www.ncbi.nlm.nih.gov/pubmed/21795275", "http://www.ncbi.nlm.nih.gov/pubmed/23573591" ], "ideal_answer": [ "Facioscapulohumeral muscular dystrophy has an autosomal dominant inheritance pattern." ], "exact_answer": [ "autosomal dominant" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918" ], "type": "factoid", "id": "52bf19c503868f1b06000001", "snippets": [ { "offsetInBeginSection": 214, "offsetInEndSection": 238, "text": "autosomal dominant FSHD1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23143600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disease, characterized by an autosomal dominant mode of inheritance, facial involvement, and selectivity and asymmetry of muscle involvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22551571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant disorder characterized by weakness of the face, upper arm, shoulder, and lower limb musculature, with an onset between the first and third decades. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525183", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 659, "text": "Clinical diagnosis is made from the distinctive pattern of weakness, autosomal-dominant inheritance, and confirmed by genetic testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795275", "endSection": "abstract" }, { "offsetInBeginSection": 1205, "offsetInEndSection": 1353, "text": " In one family together with prenatal diagnosis founder mutation in FSHD A1 gene was detected, according to the autosomal dominant (AD) inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19248726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Facioscapulohumeral muscular dystrophy (FSHD) is a primary muscle disorder with autosomal dominant inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15307599", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive myopathy with autosomal dominant inheritance remarkable for its early involvement of facial musculature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10969520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Consensual diagnostic criteria for facioscapulohumeral dystrophy (FSHD) include onset of the disease in facial or shoulder girdle muscles, facial weakness in more than 50% of affected family members, autosomal dominant inheritance in familial cases, and evidence of myopathic disease in at least one affected member without biopsy features specific to alternative diagnoses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10864616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant muscular disorder associated with a short (<35 kb) EcoRI/BlnI fragment resulting from deletion of an integral number of units of a 3.3-kb repeat located at 4q35.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10487912", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 369, "text": "In 139 families, dominant inheritance was observed in 97, a pattern compatible with germline mosaicism in 6, while sporadic cases were found in 36 families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23573591", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 368, "text": "In 139 families, dominant inheritance was observed in 97, a pattern compatible with germline mosaicism in 6, while sporadic cases were found in 36 families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7739631", "endSection": "abstract" } ] }, { "body": "Is Alu hypomethylation associated with breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20682973", "http://www.ncbi.nlm.nih.gov/pubmed/24971511" ], "ideal_answer": [ "Yes, Alu elements were found to be hypomethylated in breast cancer, especially in the HER2-enriched subtype. Furthermore, Alu hypomethylation was identified as a late event during breast cancer progression, and in invasive breast cancer, tended to be associated with negative estrogen receptor status and poor disease-free survival of the patients.", "Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer " ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1612" ], "type": "yesno", "id": "54db1d580f63c58e6e000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971511", "endSection": "title" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1241, "text": "In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971511", "endSection": "abstract" }, { "offsetInBeginSection": 1516, "offsetInEndSection": 1637, "text": "In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971511", "endSection": "abstract" }, { "offsetInBeginSection": 1709, "offsetInEndSection": 1786, "text": "Alu hypomethylation is probably a late event during breast cancer progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971511", "endSection": "abstract" }, { "offsetInBeginSection": 1792, "offsetInEndSection": 1928, "text": "prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971511", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 754, "text": "DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682973", "endSection": "abstract" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1241, "text": "DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682973", "endSection": "abstract" } ] }, { "body": "Which proteins participate in the formation of the ryanodine receptor quaternary macromolecular complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12909320", "http://www.ncbi.nlm.nih.gov/pubmed/11069905", "http://www.ncbi.nlm.nih.gov/pubmed/15205169", "http://www.ncbi.nlm.nih.gov/pubmed/22298808", "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "http://www.ncbi.nlm.nih.gov/pubmed/18620751", "http://www.ncbi.nlm.nih.gov/pubmed/18206802", "http://www.ncbi.nlm.nih.gov/pubmed/16289269", "http://www.ncbi.nlm.nih.gov/pubmed/15731387", "http://www.ncbi.nlm.nih.gov/pubmed/14638677", "http://www.ncbi.nlm.nih.gov/pubmed/9287354", "http://www.ncbi.nlm.nih.gov/pubmed/22427521" ], "ideal_answer": [ "Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin. ", "Calsequestrin (CSQ) is a Ca(2+) storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca(2+) signaling complex in the cardiac junctional sarcoplasmic reticulum (SR). Junctin, calsequestrin, triadin, and the ryanodine receptor form a quaternary complex that may be required for normal operation of Ca2+ release." ], "exact_answer": [ [ "Ryanodine receptor", "RyR" ], [ "Calsequestrin", "CASQ", "CSQ" ], [ "Triadin", "TrD", "TRN" ], [ "Junctin", "JCN", "JnC", "JUN" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0065003", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020836", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019837" ], "type": "list", "id": "54f9d3eedd3fc62544000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Calsequestrin (CSQ) is a Ca(2+) storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca(2+) signaling complex in the cardiac junctional sarcoplasmic reticulum (SR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427521", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 645, "text": "The decrease of CASQ2 is associated with a reduction in the levels of Triadin (TrD) and Junctin (JnC), two proteins that form, with CASQ2 and RyR2, a macromolecular complex devoted to control of calcium release from the sarcoplasmic reticulum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22298808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Triadin and junctin are integral sarcoplasmic reticulum membrane proteins that form a macromolecular complex with the skeletal muscle ryanodine receptor (RyR1) but their roles in skeletal muscle calcium homeostasis remain incompletely understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18620751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Junctin, a 26 kDa intra-sarcoplasmic reticulum (SR) protein, forms a quaternary complex with triadin, calsequestrin and the ryanodine receptor (RyR) at the junctional SR membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "In cardiac muscle, junctin forms a quaternary protein complex with the ryanodine receptor (RyR), calsequestrin, and triadin 1 at the luminal face of the junctional sarcoplasmic reticulum (jSR). By binding directly the RyR and calsequestrin, junctin may mediate the Ca(2+)-dependent regulatory interactions between both proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16289269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15731387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 1. This quaternary protein complex is thought to facilitate SR Ca2+ release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15205169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "In mammalian striated muscles, ryanodine receptor (RyR), triadin, junctin, and calsequestrin form a quaternary complex in the lumen of sarcoplasmic reticulum. Such intermolecular interactions contribute not only to the passive buffering of sarcoplasmic reticulum luminal Ca2+, but also to the active Ca2+ release process during excitation-contraction coupling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638677", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 213, "text": "Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12909320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Triadin 1 is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum (SR), which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), junctin, and calsequestrin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11069905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 469, "text": "Several key proteins have been localized to junctional sarcoplasmic reticulum which are important for Ca2+ release. These include the ryanodine receptor, triadin, and calsequestrin, which may associate into a stable complex at the junctional membrane. We recently purified and cloned a fourth component of this complex, junctin, which exhibits homology with triadin and is the major 125I-calsequestrin-binding protein detected in cardiac sarcoplasmic reticulum vesicles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9287354", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 993, "text": "By a combination of approaches including calsequestrin-affinity chromatography, filter overlay, immunoprecipitation assays, and fusion protein binding analyses, we find that junctin binds directly to calsequestrin, triadin, and the ryanodine receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9287354", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1731, "text": "Taken together, these results suggest that junctin, calsequestrin, triadin, and the ryanodine receptor form a quaternary complex that may be required for normal operation of Ca2+ release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9287354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15731387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Junctin, a 26 kDa intra-sarcoplasmic reticulum (SR) protein, forms a quaternary complex with triadin, calsequestrin and the ryanodine receptor (RyR) at the junctional SR membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18206802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18206802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15731387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12909320", "endSection": "abstract" } ] }, { "body": "What kind of chromatography is HILIC?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21737084", "http://www.ncbi.nlm.nih.gov/pubmed/23217321", "http://www.ncbi.nlm.nih.gov/pubmed/22946920", "http://www.ncbi.nlm.nih.gov/pubmed/23073287", "http://www.ncbi.nlm.nih.gov/pubmed/21238772", "http://www.ncbi.nlm.nih.gov/pubmed/21316059" ], "ideal_answer": [ "Hydrophilic Interaction Chromatography (HILIC)" ], "exact_answer": [ "Hydrophilic Interaction Chromatography" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002845" ], "type": "factoid", "id": "5505edac8e1671127b000005", "snippets": [ { "offsetInBeginSection": 2, "offsetInEndSection": 96, "text": "hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23217321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Hydrophilic-interaction liquid chromatography (HILIC) is a widely used technique for small polar molecule analysis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23073287", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 417, "text": "hydrophilic-interaction LC (HILIC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22946920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737084", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 107, "text": "Hydrophilic Interaction Chromatography (HILIC) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21316059", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 365, "text": "n this study a hydrophilic interaction chromatographic (HILIC) method ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21238772", "endSection": "abstract" } ] }, { "body": "What is the effect of TRH on myocardial contractility?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9225129", "http://www.ncbi.nlm.nih.gov/pubmed/1979356", "http://www.ncbi.nlm.nih.gov/pubmed/9088928", "http://www.ncbi.nlm.nih.gov/pubmed/15096458", "http://www.ncbi.nlm.nih.gov/pubmed/2848686", "http://www.ncbi.nlm.nih.gov/pubmed/1611701" ], "ideal_answer": [ "TRH improves myocardial contractility" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008437", "http://www.uniprot.org/uniprot/TRFR_RAT", "http://www.uniprot.org/uniprot/TRFR_MOUSE", "http://www.uniprot.org/uniprot/TRFR_CHICK", "http://www.disease-ontology.org/api/metadata/DOID:114", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.uniprot.org/uniprot/TRFR_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003285", "http://www.uniprot.org/uniprot/TRFR_HUMAN", "http://www.biosemantics.org/jochem#4254151", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.uniprot.org/uniprot/TRFR_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013973", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009200" ], "type": "summary", "id": "5160193d298dcd4e51000039", "snippets": [ { "offsetInBeginSection": 876, "offsetInEndSection": 1078, "text": "Acute intravenous administration of TRH to rats with ischemic cardiomyopathy caused a significant increase in heart rate, mean arterial pressure, cardiac output, stroke volume, and cardiac contractility", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15096458", "endSection": "sections.0" }, { "offsetInBeginSection": 92, "offsetInEndSection": 144, "text": "TRH can enhance cardiomyocyte contractility in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9225129", "endSection": "sections.0" }, { "offsetInBeginSection": 151, "offsetInEndSection": 257, "text": "TRH in the range of 0.1-10 mumol/l was found to exert a positive inotropic effect on cardiac contractility", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9088928", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Thyrotropin-releasing hormone (TRH) improved mean arterial pressure (MAP) and myocardial contractility (dp/dtmax, -dp/dtmax, Vpm, and Vmax)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1611701", "endSection": "sections.0" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1192, "text": "TRH improves cardiac contractility, cardiac output, and hemodynamics", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1611701", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Thyrotropin-releasing hormone (TRH) could improve mean arterial pressure (MAP), myocardial contractile parameters (+/- dp/dtmax, Vpm and Vmax)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1979356", "endSection": "sections.0" }, { "offsetInBeginSection": 170, "offsetInEndSection": 281, "text": "TRH increased the contractile force of muscles dose-dependently without changing the time course of contraction", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2848686", "endSection": "sections.0" }, { "offsetInBeginSection": 522, "offsetInEndSection": 619, "text": "TRH potentiated the response of contractile force to increasing extracellular Ca2+ concentration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2848686", "endSection": "sections.0" }, { "offsetInBeginSection": 857, "offsetInEndSection": 959, "text": "TRH has a positive inotropic effect at least partly due to an increase in the slow inward Ca2+ current", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2848686", "endSection": "sections.0" }, { "offsetInBeginSection": 1118, "offsetInEndSection": 1218, "text": "Thus, TRH improves cardiac contractility, cardiac output, and hemodynamics during hemorrhagic shock.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1611701", "endSection": "sections.0" } ] }, { "body": "Proteomic analyses need prior knowledge of the organism complete genome. Is the complete genome of the bacteria of the genus Arthrobacter available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28904741", "http://www.ncbi.nlm.nih.gov/pubmed/28450506", "http://www.ncbi.nlm.nih.gov/pubmed/21677849", "http://www.ncbi.nlm.nih.gov/pubmed/28315371", "http://www.ncbi.nlm.nih.gov/pubmed/23039946", "http://www.ncbi.nlm.nih.gov/pubmed/28642378", "http://www.ncbi.nlm.nih.gov/pubmed/28138355" ], "ideal_answer": [ "Yes, the complete genome sequence of Arthrobacter (two strains) is deposited in GenBank." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001173", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ], "type": "yesno", "id": "51593dc8d24251bc05000099", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Complete genome sequence of Arthrobacter phenanthrenivorans type strain (Sphe3).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21677849", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Complete genome sequence and metabolic potential of the quinaldine-degrading bacterium Arthrobacter sp. Rue61a.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23039946", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 387, "text": "Here, we described the high quality draft genome sequence, annotations and the features ofArthrobactersp. B6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28138355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Complete genome sequence of Arthrobacter sp. ZXY-2 associated with effective atrazine degradation and salt adaptation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28315371", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "We announce here the draft genome sequence ofArthrobactersp. strain EpSL27, isolated from the stem and leaves of the medicinal plantEchinacea purpureaand able to inhibit human-pathogenic bacterial strains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28642378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "We report here the 4.6-Mb genome sequence of a nylon oligomer-degrading bacterium,Arthrobactersp. strain KI72.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28450506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Arthrobacter alpinusR3.8 is a psychrotolerant bacterial strain isolated from a soil sample obtained at Rothera Point, Adelaide Island, close to the Antarctic Peninsula. Strain R3.8 was sequenced in order to help discover potential cold active enzymes with biotechnological applications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28904741", "endSection": "abstract" } ] }, { "body": "What is the structural fold of bromodomain proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17498659", "http://www.ncbi.nlm.nih.gov/pubmed/17148447", "http://www.ncbi.nlm.nih.gov/pubmed/17694091", "http://www.ncbi.nlm.nih.gov/pubmed/10827952", "http://www.ncbi.nlm.nih.gov/pubmed/17848202", "http://www.ncbi.nlm.nih.gov/pubmed/17582821", "http://www.ncbi.nlm.nih.gov/pubmed/11090279", "http://www.ncbi.nlm.nih.gov/pubmed/17274598", "http://www.ncbi.nlm.nih.gov/pubmed/10365964" ], "ideal_answer": [ "The structure fold of the bromodomains is an all-alpha-helical fold, which includes a left-handed four-helix bundle topology, with two short additional helices in a long connecting loop." ], "exact_answer": [ "All-alpha-helical fold" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506" ], "type": "factoid", "id": "56e2cec751531f7e33000015", "snippets": [ { "offsetInBeginSection": 780, "offsetInEndSection": 1028, "text": "These new studies also support the notion that functional diversity of a conserved bromodomain structural fold is achieved by evolutionary changes of structurally flexible amino-acid sequences in the ligand binding site such as the ZA and BC loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17694091", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1046, "text": "Although the overall fold resembles the bromodomains from other proteins, significant differences can be found in loop regions, especially in the ZA loop in which a two amino acids insertion is involved in an uncommon pi-helix, termed piD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17848202", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 905, "text": "In addition to a typical all-alpha-helical fold that was observed in the bromodomains, we observed for the first time a small beta-sheet in the ZA loop region of the BRG1 protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17582821", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 665, "text": "Here, we report the crystal structure of the N-terminal bromodomain (BD1, residues 74-194) of human BRD2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17148447", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 882, "text": "This is the first observation of a homodimer among the known bromodomain structures, through the buried hydrophobic core region at the interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17148447", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 762, "text": "The Brg1 bromodomain conserves the left-handed, four-helix bundle topology found in other bromodomain structures. However, the alphaZ helix of Brg1 bromodomain is about 4 residues shorter relative to previously published bromodomain structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17274598", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 626, "text": "Here, we report the solution structure of BRD7 bromodomain determined by NMR spectroscopy, and its binding specificity revealed by NMR titration with several acetylated histone peptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17498659", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 510, "text": "The 2.1 angstrom crystal structure of the double bromodomain reveals two side-by-side, four-helix bundles with a highly polarized surface charge distribution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10827952", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 249, "text": "The structure has a left-handed four-helix bundle topology, with two short additional helices in a long connecting loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11090279", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 598, "text": "The structure reveals an unusual left-handed up-and-down four-helix bundle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10365964", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 906, "text": "In addition to a typical all-alpha-helical fold that was observed in the bromodomains, we observed for the first time a small beta-sheet in the ZA loop region of the BRG1 protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17582821", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 813, "text": "In addition to a typical all-alpha-helical fold that was observed in the bromodomains,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17582821", "endSection": "abstract" } ] }, { "body": "List the endoscopic diagnoses that have been reported in children with autism", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "http://www.ncbi.nlm.nih.gov/pubmed/22607127", "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "http://www.ncbi.nlm.nih.gov/pubmed/9585670", "http://www.ncbi.nlm.nih.gov/pubmed/10547242", "http://www.ncbi.nlm.nih.gov/pubmed/12907332" ], "ideal_answer": [ "Endoscopic examinations in autistic children have been reported to show : I or II reflux esophagitis, Achalasia, chronic gastritis and chronic duodenitis, mild acute and chronic inflammation of the small bowel and colorectum and Ileo-colonic lymphoid nodular hyperplasia (LNH). \nThe number of Paneth's cells in the duodenal crypts was found to be significantly elevated in autistic children compared with non-autistic control subjects. Low intestinal carbohydrate digestive enzyme activity was reported although there was no abnormality found in pancreatic function. Autistic children have ben reported to have an increased pancreatico-biliary fluid output after intravenous secretin administration." ], "exact_answer": [ [ "Reflux esophagitis" ], [ "Achalasia" ], [ "chronic gastritis" ], [ "chronic duodenitis" ], [ "inflammation of the small bowel and colorectum" ], [ "Ileo-colonic lymphoid nodular hyperplasia (LNH)" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:12849", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016099", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004724" ], "type": "list", "id": "515deafd298dcd4e51000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Autism and esophageal achalasia in childhood: a possible correlation?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22607127", "endSection": "title" }, { "offsetInBeginSection": 801, "offsetInEndSection": 902, "text": "In the last case, a 15-year-old male underwent barium swallow and endoscopy that confirmed achalasia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22607127", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 258, "text": "Intestinal mucosal pathology, characterized by ileo-colonic lymphoid nodular hyperplasia (LNH) and mild acute and chronic inflammation of the colorectum, small bowel and stomach, has been reported in children with autistic spectrum disorder (ASD)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "endSection": "sections.0" }, { "offsetInBeginSection": 2154, "offsetInEndSection": 2308, "text": "Ileo-colonic LNH is a characteristic pathological finding in children with ASD and gastrointestinal symptoms, and is associated with mucosal inflammation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "endSection": "sections.0" }, { "offsetInBeginSection": 2386, "offsetInEndSection": 2481, "text": "The data support the hypothesis that LNH is a significant pathological finding in ASD children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 285, "text": "A relationship between autism and gastrointestinal (GI) immune dysregulation has been postulated based on incidence of GI complaints as well as macroscopically observed lymphonodular hyperplasia and microscopically determined enterocolitis in pediatric patients with autism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12907332", "endSection": "sections.0" }, { "offsetInBeginSection": 1980, "offsetInEndSection": 2057, "text": "These data fail to support an association between autism and GI inflammation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12907332", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 172, "text": "Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "endSection": "sections.0" }, { "offsetInBeginSection": 173, "offsetInEndSection": 752, "text": "This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "endSection": "sections.0" }, { "offsetInBeginSection": 1265, "offsetInEndSection": 1889, "text": "Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "endSection": "sections.0" }, { "offsetInBeginSection": 177, "offsetInEndSection": 390, "text": "Thirty-six children (age: 5.7 +/- 2 years, mean +/- SD) with autistic disorder underwent upper gastrointestinal endoscopy with biopsies, intestinal and pancreatic enzyme analyses, and bacterial and fungal cultures", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10547242", "endSection": "sections.0" }, { "offsetInBeginSection": 524, "offsetInEndSection": 1235, "text": "Histologic examination in these 36 children revealed grade I or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15, and chronic duodenitis in 24. The number of Paneth's cells in the duodenal crypts was significantly elevated in autistic children compared with non-autistic control subjects. Low intestinal carbohydrate digestive enzyme activity was reported in 21 children (58.3%), although there was no abnormality found in pancreatic function. Seventy-five percent of the autistic children (27/36) had an increased pancreatico-biliary fluid output after intravenous secretin administration. Nineteen of the 21 patients with diarrhea had significantly higher fluid output than those without diarrhea.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10547242", "endSection": "sections.0" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1583, "text": "Unrecognized gastrointestinal disorders, especially reflux esophagitis and disaccharide malabsorption, may contribute to the behavioral problems of the non-verbal autistic patients. The observed increase in pancreatico-biliary secretion after secretin infusion suggests an upregulation of secretin receptors in the pancreas and liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10547242", "endSection": "sections.0" }, { "offsetInBeginSection": 10, "offsetInEndSection": 297, "text": "three children with autistic spectrum disorders who underwent upper gastrointestinal endoscopy and intravenous administration of secretin to stimulate pancreaticobiliary secretion. All three had an increased pancreaticobiliary secretory response when compared with nonautistic patients (", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9585670", "endSection": "sections.0" } ] }, { "body": "What are the outcomes of Renal sympathetic denervation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21247927", "http://www.ncbi.nlm.nih.gov/pubmed/22573363", "http://www.ncbi.nlm.nih.gov/pubmed/23176687", "http://www.ncbi.nlm.nih.gov/pubmed/23541665", "http://www.ncbi.nlm.nih.gov/pubmed/23774592", "http://www.ncbi.nlm.nih.gov/pubmed/24029963", "http://www.ncbi.nlm.nih.gov/pubmed/23890950", "http://www.ncbi.nlm.nih.gov/pubmed/23514712", "http://www.ncbi.nlm.nih.gov/pubmed/23819768" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0121834", "o": "U004557" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": 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The complication rate was minimal.\nRenal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013563", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013562", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003714", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012077" ], "type": "summary", "id": "532624ae600967d132000005", "snippets": [ { "offsetInBeginSection": 544, "offsetInEndSection": 703, "text": "Significant decreases and progressively higher reductions of systolic and diastolic blood pressure were observed after RSD. The complication rate was minimal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029963", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 866, "text": "In conclusion, the RSD presents itself as an effective and safe approach to resistant hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029963", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 854, "text": "Renal sympathetic denervation delivers not only a decrease in blood pressure levels but also renal as well as systemic sympathetic nerve activity. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which implies no counterregulatory mechanism or re-innervation of afferent renal sympathetic nerve so far.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890950", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 811, "text": "Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23819768", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 497, "text": "Clinical trials of renal sympathetic denervation have shown significant reductions in blood pressure in these patients. Renal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23774592", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 1339, "text": "Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23541665", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1447, "text": "Clinical evaluation of selective renal sympathetic denervation demonstrated a decrease of renal norepinephrine spillover and renin activity, an increase of renal plasma flow, and has confirmed clinically significant, sustained reductions in blood pressure in patients with resistant hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23514712", "endSection": "abstract" }, { "offsetInBeginSection": 1254, "offsetInEndSection": 1407, "text": "In addition to drug treatment, baroreceptor stimulation therapy and renal sympathetic denervation are promising new approaches in this group of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176687", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 1553, "text": "Early clinical evaluation with catheter-based, selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity, increased renal plasma flow, and has demonstrated clinically significant, sustained reductions in blood pressure. The SYMPLICITY HTN-3 Trial is a pivotal study designed as a prospective, randomized, masked procedure, single-blind trial evaluating the safety and effectiveness of catheter-based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes (at least one of which is a diuretic) at maximal tolerable doses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22573363", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 761, "text": "Novel procedure- and device-based strategies to control hypertension include renal sympathetic denervation and baroreflex sensitization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21247927", "endSection": "abstract" } ] }, { "body": "Which MAP kinase phosphorylates the transcription factor c-jun?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24113186", "http://www.ncbi.nlm.nih.gov/pubmed/24300195", "http://www.ncbi.nlm.nih.gov/pubmed/24272171", "http://www.ncbi.nlm.nih.gov/pubmed/24291243", "http://www.ncbi.nlm.nih.gov/pubmed/24252081", "http://www.ncbi.nlm.nih.gov/pubmed/15228586", "http://www.ncbi.nlm.nih.gov/pubmed/23028407", "http://www.ncbi.nlm.nih.gov/pubmed/15637069", "http://www.ncbi.nlm.nih.gov/pubmed/24285252", "http://www.ncbi.nlm.nih.gov/pubmed/23385061", "http://www.ncbi.nlm.nih.gov/pubmed/24321566", "http://www.ncbi.nlm.nih.gov/pubmed/23147205", "http://www.ncbi.nlm.nih.gov/pubmed/8607977", "http://www.ncbi.nlm.nih.gov/pubmed/15708845", "http://www.ncbi.nlm.nih.gov/pubmed/24139673", "http://www.ncbi.nlm.nih.gov/pubmed/24270002", "http://www.ncbi.nlm.nih.gov/pubmed/24144051", "http://www.ncbi.nlm.nih.gov/pubmed/24321066" ], "ideal_answer": [ "c-Jun is phosphorylated by c-Jun NH2-terminal kinase (JNK).", "An in vitro kinase assay revealed that c-Jun phosphorylation is primarily mediated via activated c-Jun N-terminal protein kinase (JNK)." ], "exact_answer": [ "c-Jun NH2-terminal kinase", "JNK" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007257", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007258", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016755" ], "type": "factoid", "id": "5518e7da622b194345000004", "snippets": [ { "offsetInBeginSection": 955, "offsetInEndSection": 987, "text": " c-Jun NH2-terminal kinase (JNK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321566", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 294, "text": " c-jun N-terminal kinase (JNK) of mitogen-activated protein kinase (MAPK) family ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321066", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 955, "text": "-Jun N-terminal kinase (JNK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24300195", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 859, "text": "activated c-Jun N-terminal kinase (JNK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291243", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1006, "text": "-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathways", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285252", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 454, "text": " c-Jun N-terminal kinases (JNK) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24272171", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1116, "text": " including c-Jun N-terminal kinase, c-Jun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24270002", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 118, "text": "The c-Jun N-terminal kinase (JNK) is thought to be involved in inflammation, proliferation and apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252081", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 828, "text": " c-Jun NH2-terminal protein kinases (JNK), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24144051", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1357, "text": " c-Jun N-terminal kinase (JNK) phosphorylation, c-Jun phosphorylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24139673", "endSection": "abstract" }, { "offsetInBeginSection": 1820, "offsetInEndSection": 1893, "text": "JNK phosphorylated recombinant c-Jun at T91/T93 in a T95-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24113186", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 898, "text": " c-Jun N-terminal kinase (JNK) MAPKs (mitogen-activated protein kinases)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15228586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "c-Jun N-terminal kinases (JNKs) are a group of mitogen-activated protein kinase family members that are important in regulating cell growth, proliferation, and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15637069", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 943, "text": "Jun and Fos transcriptional activities are also regulated by phosphorylation as a result of the activation of intracellular signaling cascades. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been readily documented, whereas a role for Fos proteins in UV-mediated responses and the identification of Fos-activating kinases has remained elusive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15708845", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 388, "text": "An in vitro kinase assay revealed that the resultant c-Jun phosphorylation was primarily mediated via activated c-Jun N-terminal protein kinase (JNK).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The c-Jun N-terminal kinase (JNK) pathway forms part of the mitogen-activated protein kinase (MAPK) signaling pathways comprising a sequential three-tiered kinase cascade. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23147205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family and are activated by environmental stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028407", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 890, "text": "JNK phosphorylates and regulates the activity of transcription factors other than c-Jun, including ATF2, Elk-1, p53 and c-Myc and non-transcription factors, such as members of the Bcl-2 family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028407", "endSection": "abstract" }, { "offsetInBeginSection": 1932, "offsetInEndSection": 2132, "text": "A candidate for this extended family of MAP kinases is the c-Jun NH2-terminal kinase (Jnk), which binds to and phosphorylates the transcription factor c-Jun at the activating sites Ser-63 and Ser-73.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8607977", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 386, "text": "An in vitro kinase assay revealed that the resultant c-Jun phosphorylation was primarily mediated via activated c-Jun N-terminal protein kinase (JNK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385061", "endSection": "abstract" }, { "offsetInBeginSection": 1953, "offsetInEndSection": 2151, "text": "A candidate for this extended family of MAP kinases is the c-Jun NH2-terminal kinase (Jnk), which binds to and phosphorylates the transcription factor c-Jun at the activating sites Ser-63 and Ser-73", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8607977", "endSection": "abstract" } ] }, { "body": "What is the meaning of the acronym \"TAILS\" used in protein N-terminomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20305284", "http://www.ncbi.nlm.nih.gov/pubmed/21604127", "http://www.ncbi.nlm.nih.gov/pubmed/22577022", "http://www.ncbi.nlm.nih.gov/pubmed/21604129", "http://www.ncbi.nlm.nih.gov/pubmed/23667905", "http://www.ncbi.nlm.nih.gov/pubmed/22367194" ], "ideal_answer": [ "TAILS stands for \"Terminal Amine Isotopic Labeling of Substrates\"" ], "exact_answer": [ "TAILS: Terminal Amine Isotopic Labeling of Substrates" ], "concepts": [ "http://www.uniprot.org/uniprot/TERM_DROME", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506" ], "type": "factoid", "id": "530a5117970c65fa6b000007", "snippets": [ { "offsetInBeginSection": 127, "offsetInEndSection": 305, "text": ". It is important to identify what proteins are substrates of proteases and where their cleavage sites are so as to reveal the molecular mechanisms and specificity of signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21604127", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 304, "text": "It is important to identify what proteins are substrates of proteases and where their cleavage sites are so as to reveal the molecular mechanisms and specificity of signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21604127", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 712, "text": "analysis of N- terminomics data generated by terminal amine isotopic labeling of substrates (TAILS) enables high confidence peptide to protein assignment, protein N-terminal characterization and annotation, and for protease analysis readily allows protease substrate discovery with high confidence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23667905", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 571, "text": "Several approaches to studying proteolytic activity as it relates to biology, pathophysiology, and drug therapy have been published, including the recently described terminal amine isotopic labeling of substrates (TAILS) strategy by Kleifeld and colleagues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577022", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1418, "text": " The degradomics screen terminal amine isotopic labeling of substrates (TAILS), which enriches for neo-N-terminal peptides of cleaved substrates, was used to identify 58 new native substrates in fibroblast secretomes after incubation with MT6-MMP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22367194", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 603, "text": " Here we present in detail the steps required to perform our recently described approach we call Terminal Amine Isotopic Labeling of Substrates (TAILS), a combined N-terminomics and protease substrate discovery degradomics platform for the simultaneous quantitative and global analysis of the N-terminome and proteolysis in one MS/MS experiment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21604129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Identification of proteolytic products and natural protein N-termini by Terminal Amine Isotopic Labeling of Substrates (TAILS).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21604129", "endSection": "title" }, { "offsetInBeginSection": 717, "offsetInEndSection": 955, "text": " Incorporating iTRAQ whole protein labeling with terminal amine isotopic labeling of substrates (iTRAQ-TAILS) to enrich the N-terminome by negative selection of the blocked mature original N-termini and neo-N-termini has many advantages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20305284", "endSection": "abstract" } ] }, { "body": "Do mutations of AKT1 occur in meningiomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25146167", "http://www.ncbi.nlm.nih.gov/pubmed/23475883", "http://www.ncbi.nlm.nih.gov/pubmed/23348505", "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "http://www.ncbi.nlm.nih.gov/pubmed/24096618", "http://www.ncbi.nlm.nih.gov/pubmed/25857641" ], "ideal_answer": [ "Yes, AKT1 mutation occurs in meningiomas." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4264173", "http://www.disease-ontology.org/api/metadata/DOID:3565", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579" ], "type": "yesno", "id": "56bf365eef6e39474100000e", "snippets": [ { "offsetInBeginSection": 921, "offsetInEndSection": 1122, "text": "The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25857641", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 611, "text": "A mutation in PIK3CA or AKT1 was found in around 9 % of the cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25146167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096618", "endSection": "title" }, { "offsetInBeginSection": 424, "offsetInEndSection": 744, "text": "AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096618", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1088, "text": "We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "SMO and AKT1 mutations occur in non-NF2 meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475883", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "endSection": "title" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1002, "text": " A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23348505", "endSection": "title" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1201, "text": "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "SMO and AKT1 mutations occur in non-NF2 meningiomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475883", "endSection": "title" }, { "offsetInBeginSection": 921, "offsetInEndSection": 1121, "text": "The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25857641", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 1001, "text": "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23348505", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475883", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 1106, "text": "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 1003, "text": "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. 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"N0000177931" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A15872952", "o": "623400" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A15872952", "o": "RXNORM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18124823", "o": "LOINC" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18129219", "o": "LOINC" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16026747", "o": "Multum" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16029231", "o": "Multum" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17686104", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17694684", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16388630", "o": "National Drug File" } ], "ideal_answer": [ "Lacosamide is an anti-epileptic drug, licensed for refractory partial-onset seizures. In addition to this, it has demonstrated analgesic activity in various animal models. Apart from this, LCM has demonstrated potent effects in animal models for a variety of CNS disorders like schizophrenia and stress induced anxiety." ], "exact_answer": [ [ "epilepsy", "refractory epilepsy", "refractory partial-onset seizures" ], [ "analgesic" ], [ "CNS disorders" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4267957" ], "type": "list", "id": "52bf202003868f1b06000018", "snippets": [ { "offsetInBeginSection": 301, "offsetInEndSection": 457, "text": "The current article presents a concise review of network theory and its application to the characterization of AED use in children with refractory epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23648276", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 892, "text": "Furthermore, first generation AEDs were often discontinued, while lacosamide and topiramate were most likely to be initiated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23648276", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1593, "text": "Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288091", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1658, "text": "The first examples are carbamazepine, gabapentin, and lacosamide as drugs well established in epilepsy market as well as drug candidates such as valnoctamide, and other valproic acid derivatives, novel biphenyl pyrazole derivatives, etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21861814", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 756, "text": "Two additional AEDs, lacosamide and eslicarbazepine acetate, have been licensed recently for a more traditional indication, refractory partial-onset seizures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21301338", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1679, "text": "A discussion is made of recent findings that the atypical antidepressant tianeptine increases CRMP2 expression, whereas other, neuroactive small molecules including the epilepsy drug lacosamide and the natural brain metabolite lanthionine ketimine appear to bind CRMP2 directly with concomitant affects on neural structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21271304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Lacosamide (LCM) is a newer antiepileptic drug with a dual mode of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20677583", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 700, "text": " It has shown potent and broad neuroprotective effects in vitro and in vivo animal models making it a potential candidate for long term treatment of epilepsy. In addition to this, it has demonstrated analgesic activity in various animal models. Apart from this, LCM has demonstrated potent effects in animal models for a variety of CNS disorders like schizophrenia and stress induced anxiety. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20677583", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 985, "text": "Clinical trials have also suggested that LCM is a safe, effective, and well tolerated adjunctive treatment for reduction of seizure frequency in patients with highly refractory, partial seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20677583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 490, "text": "Lacosamide (LCM), (SPM 927, (R)-2-acetamido-N-benzyl-3-methoxypropionamide, previously referred to as harkoseride or ADD 234037) is a member of a series of functionalized amino acids that were specifically synthesized as anticonvulsive drug candidates. LCM has demonstrated antiepileptic effectiveness in different rodent seizure models and antinociceptive potential in experimental animal models that reflect distinct types and symptoms of neuropathic as well as chronic inflammatory pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17461888", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 602, "text": "Recent results suggest that LCM has a dual mode of action underlying its anticonvulsant and analgesic activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17461888", "endSection": "abstract" }, { "offsetInBeginSection": 1750, "offsetInEndSection": 1976, "text": "Currently, LCM is in a late stage of clinical development as an adjunctive treatment for patients with uncontrolled partial-onset seizures, and it is being assessed as monotherapy in patients with painful diabetic neuropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17461888", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 491, "text": "Lacosamide was effective against sound-induced seizures in the genetically susceptible Frings mouse, against maximal electroshock test (MES)-induced seizures in rats and mice, in the rat hippocampal kindling model of partial seizures, and in the 6Hz model of psychomotor seizures in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17433624", "endSection": "abstract" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1206, "text": "Lacosamide was inactive against clonic seizures induced by subcutaneous administration of the chemoconvulsants pentylenetetrazol, bicuculline, and picrotoxin, but it did inhibit NMDA-induced seizures in mice and showed full efficacy in the homocysteine model of epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17433624", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1608, "text": "These results suggest that lacosamide may have the potential to be clinically useful for at least the treatment of generalized tonic-clonic and partial-onset epilepsies, and support ongoing clinical trials in these indications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17433624", "endSection": "abstract" } ] }, { "body": "Which fusion protein is involved in the development of Ewing sarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25432018", "http://www.ncbi.nlm.nih.gov/pubmed/21979944", "http://www.ncbi.nlm.nih.gov/pubmed/16206264", "http://www.ncbi.nlm.nih.gov/pubmed/18256529", "http://www.ncbi.nlm.nih.gov/pubmed/25162919", "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "http://www.ncbi.nlm.nih.gov/pubmed/22241085", "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "http://www.ncbi.nlm.nih.gov/pubmed/25483190", "http://www.ncbi.nlm.nih.gov/pubmed/17250957", "http://www.ncbi.nlm.nih.gov/pubmed/22723308", "http://www.ncbi.nlm.nih.gov/pubmed/23750284", "http://www.ncbi.nlm.nih.gov/pubmed/24481407", "http://www.ncbi.nlm.nih.gov/pubmed/20691659", "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "http://www.ncbi.nlm.nih.gov/pubmed/17453169", "http://www.ncbi.nlm.nih.gov/pubmed/18485618", "http://www.ncbi.nlm.nih.gov/pubmed/23894528", "http://www.ncbi.nlm.nih.gov/pubmed/21680731" ], "ideal_answer": [ "Ewing sarcoma is the second most common bone malignancy in children and young adults. In almost 95% of the cases, it is driven by oncogenic fusion protein EWS/FLI1, which acts as an aberrant transcription factor, that upregulates or downregulates target genes, leading to cellular transformation." ], "exact_answer": [ "EWS/FLI1" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3368", "http://www.disease-ontology.org/api/metadata/DOID:4980", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512" ], "type": "factoid", "id": "552fac4fbc4f83e828000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Ewing sarcoma is the second most common bone malignancy in children and young adults. It is driven by oncogenic fusion proteins (i.e. EWS/FLI1) acting as aberrant transcription factors that upregulate and downregulate target genes, leading to cellular transformation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "EWS/FLI-1 oncoprotein subtypes impose different requirements for transformation and metastatic activity in a murine model", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17453169", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Ewing sarcoma/primitive neuroectodermal tumors (EWS/PNET) are characterized by specific chromosomal translocations most often generating a chimeric EWS/FLI-1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17453169", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 912, "text": "The resulting EWS-FLI-1 fusion protein is believed to behave as an aberrant transcriptional activator that contributes to ESFT development by altering the expression of its target genes in a permissive cellular environment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17250957", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 590, "text": "Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The orphan nuclear receptor DAX1 is up-regulated by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16206264", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 553, "text": "The Ewing family of tumors harbors chromosomal translocations that join the N-terminal region of the EWS gene with the C-terminal region of several transcription factors of the ETS family, mainly FLI1, resulting in chimeric transcription factors that play a pivotal role in the pathogenesis of Ewing tumors. To identify downstream targets of the EWS/FLI1 fusion protein, we established 293 cells expressing constitutively either the chimeric EWS/FLI1 or wild type FLI1 proteins and used cDNA arrays to identify genes differentially regulated by EWS/FLI1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16206264", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1616, "text": "The high levels of DAX1 found in Ewing tumors and its potent transcriptional repressor activity suggest that the oncogenic effect of EWS/FLI1 may be mediated, at least in part, by the up-regulation of DAX1 expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16206264", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 589, "text": "Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Ewing sarcoma family tumors (ESFT) are highly aggressive and highly metastatic tumors caused by a chromosomal fusion between the Ewing sarcoma protein (EWS) with the transcription factor FLI-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22241085", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 774, "text": "EWS-FLI1 is a fusion protein that results from the pathognomonic translocation of Ewing sarcoma (ES).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24481407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 207, "text": "Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Blocking the road, stopping the engine or killing the driver? Advances in targeting EWS/FLI-1 fusion in Ewing sarcoma as novel therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25162919", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Fusion of the EWS gene to FLI1 produces a fusion oncoprotein that drives an aberrant gene expression program responsible for the development of Ewing sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894528", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 911, "text": "Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewings sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979944", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Ewing sarcoma family of tumors (ESFT) is a group of aggressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription factor up-regulating specific target genes, such as neuropeptide Y (NPY) and its Y1 and Y5 receptors (Y5Rs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691659", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 591, "text": "Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723308", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 503, "text": "The EWS-ETS fusion is causative in the development of Ewing's tumour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18485618", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 913, "text": "The resulting EWS-FLI-1 fusion protein is believed to behave as an aberrant transcriptional activator that contributes to ESFT development by altering the expression of its target genes in a permissive cellular environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17250957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing's sarcoma family tumors (ESFT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25432018", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 206, "text": "Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "endSection": "abstract" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1496, "text": "Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 817, "text": "Thus, we developed a highly validated transcriptional profile for the EWS/FLI fusion protein and identified a critical target gene in Ewing's sarcoma development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Our understanding of Ewing's sarcoma development mediated by the EWS/FLI fusion protein has been limited by a lack of knowledge regarding the tumor cell of origin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 614, "text": "Ewing's sarcomas are characterized by recurrent chromosomal translocations expressing EWS-ETS fusion proteins, the most common of which is EWS-FLI.(1-5) EWS-FLI is an oncogenic transcription factor that regulates genes involved in tumorigenesis.(6,7) Because the Ewing's sarcoma cell of origin remains unknown, a variety of model systems have been developed to study EWS-FLI fusions,(8-14) and multiple microarray experiments describing potential EWS-FLI target genes have been reported.(8,10,11,13,15-21) Each model has potential benefits and drawbacks, but a large-scale comparison of these has not been reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256529", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 147, "text": "Most cases of Ewing's sarcoma express the EWS/FLI fusion protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "endSection": "abstract" } ] }, { "body": "List Hemolytic Uremic Syndrome Triad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25011592", "http://www.ncbi.nlm.nih.gov/pubmed/25765799", "http://www.ncbi.nlm.nih.gov/pubmed/8589282", "http://www.ncbi.nlm.nih.gov/pubmed/25345382", "http://www.ncbi.nlm.nih.gov/pubmed/7487540", "http://www.ncbi.nlm.nih.gov/pubmed/2831711", "http://www.ncbi.nlm.nih.gov/pubmed/19227723", "http://www.ncbi.nlm.nih.gov/pubmed/26265890", "http://www.ncbi.nlm.nih.gov/pubmed/20499172", "http://www.ncbi.nlm.nih.gov/pubmed/17705684", "http://www.ncbi.nlm.nih.gov/pubmed/20865638", "http://www.ncbi.nlm.nih.gov/pubmed/16006690", "http://www.ncbi.nlm.nih.gov/pubmed/20209841", "http://www.ncbi.nlm.nih.gov/pubmed/16387683", "http://www.ncbi.nlm.nih.gov/pubmed/24516709", "http://www.ncbi.nlm.nih.gov/pubmed/25280590", "http://www.ncbi.nlm.nih.gov/pubmed/24161037", "http://www.ncbi.nlm.nih.gov/pubmed/24548192", "http://www.ncbi.nlm.nih.gov/pubmed/19625716", "http://www.ncbi.nlm.nih.gov/pubmed/23380391", "http://www.ncbi.nlm.nih.gov/pubmed/22956028" ], "ideal_answer": [ "Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of anaemia, thrombocytopenia, renal failure." ], "exact_answer": [ [ "anaemia" ], [ "thrombocytopenia" ], [ "renal failure" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006463", "http://www.disease-ontology.org/api/metadata/DOID:12554" ], "type": "list", "id": "56be0da3ef6e394741000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26265890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25765799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Atypical hemolytic uremic syndrome (aHUS) is a relatively rare disorder described by the triad of hemolytic anemia, thrombocytopenia, and renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25345382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 531, "text": "Until recently, atypical hemolytic uremic syndrome (aHUS), conventionally defined in the pediatric literature as a syndrome of the triad of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia without a prodrome of hemorrhagic diarrhea, has received little attention in adult practice because the patients are commonly given the diagnosis of thrombotic thrombocytopenic purpura (TTP) or TTP/HUS and treated as TTP with plasma exchange, augmented in refractory cases with rituximab and sometimes even splenectomy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25280590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24548192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Hemolyitic uremic syndrome (HUS), characterized by triad of acute kidney injury, thrombocytopenia, and hemolytic anemia, has considerable morbidity and mortality and is known to be associated with diarrheal illness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24516709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 530, "text": "Until recently, atypical hemolytic uremic syndrome (aHUS), conventionally defined in the pediatric literature as a syndrome of the triad of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia without a prodrome of hemorrhagic diarrhea, has received little attention in adult practice because the patients are commonly given the diagnosis of thrombotic thrombocytopenic purpura (TTP) or TTP/HUS and treated as TTP with plasma exchange, augmented in refractory cases with rituximab and sometimes even splenectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25280590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Hemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20499172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24161037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The hemolytic-uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Atypical hemolytic uremic syndrome (aHUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Hemolytic uremic syndrome is a rare condition compromising the clinical triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Hemolytic Uremic Syndrome (HUS) consists ofa triad of acquired hemolytic anemia, thrombocytopenia, and renal failure that occurs acutely in otherwise healthy individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19227723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "The hemolytic-uremic syndrome is a pathology characterized by a triad consisting of acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia, with complications of the central nervous system arising in a considerable number of cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7487540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Hemolytic uremic syndrome, one of the common causes of acute renal failure in children, is characterized by the triad of microangiopathy, haemolytic anemia, thrombocytopenia and acute renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20209841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16387683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24516709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Hemolytic uremic syndrome (HUS) is a disorder characterized by the presence of the classic triad: microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Hemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20499172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Hemolytic uremic syndrome (HUS) is a severe disease characterized by the clinical triad of hemolytic anemia, thrombocytopenia, and acute renal failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20865638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Hemolytic uremic syndrome is a rare condition compromising the clinical triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Hemolytic uremic syndrome is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17705684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Hemolytic uremic syndrome is a rare entity in patients with carcinoma and presents with a triad of renal insufficiency, microangiopathic hemolytic anemia, and thrombocytopenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2831711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Hemolytic Uremic Syndrome (HUS) consists ofa triad of acquired hemolytic anemia, thrombocytopenia, and renal failure that occurs acutely in otherwise healthy individuals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19227723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Hemolytic Uremic Syndrome (HUS) consists ofa triad of acquired hemolytic anemia, thrombocytopenia, and renal failure that occurs acutely in otherwise healthy individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19227723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 464, "text": "Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes adult or pediatric hemolytic uremic syndrome, can be associated with or triggered by diverse conditions such as verocytotoxin-producing Escherichia coli, viral infections, pregnancy, malignant hypertension, scleroderma, renal radiation, allograft rejection, lupus erythematosus, and assorted medications such as mitomycin C, cyclosporine, and oral contraceptives.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8589282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Hemolytic uremic syndrome, one of the common causes of acute renal failure in children, is characterized by the triad of microangiopathy, haemolytic anemia, thrombocytopenia and acute renal failure. The diarrhoea-associated Hemolytic uremic syndrome is usually termed as a typical Hemolytic uremic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20209841", "endSection": "abstract" } ] }, { "body": "Does physical activity influence gut hormones?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2888163", "http://www.ncbi.nlm.nih.gov/pubmed/23402716", "http://www.ncbi.nlm.nih.gov/pubmed/18987287", "http://www.ncbi.nlm.nih.gov/pubmed/11321513", "http://www.ncbi.nlm.nih.gov/pubmed/21554896", "http://www.ncbi.nlm.nih.gov/pubmed/22619704", "http://www.ncbi.nlm.nih.gov/pubmed/19158129", "http://www.ncbi.nlm.nih.gov/pubmed/16942616", "http://www.ncbi.nlm.nih.gov/pubmed/15795476", "http://www.ncbi.nlm.nih.gov/pubmed/20690071", "http://www.ncbi.nlm.nih.gov/pubmed/23111564", "http://www.ncbi.nlm.nih.gov/pubmed/19737911", "http://www.ncbi.nlm.nih.gov/pubmed/21615652", "http://www.ncbi.nlm.nih.gov/pubmed/17470516", "http://www.ncbi.nlm.nih.gov/pubmed/21927572", "http://www.ncbi.nlm.nih.gov/pubmed/20061436" ], "ideal_answer": [ "Yes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444" ], "type": "yesno", "id": "5158644cd24251bc0500008e", "snippets": [ { "offsetInBeginSection": 1052, "offsetInEndSection": 1259, "text": "Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19737911", "endSection": "sections.0" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1430, "text": "A decrease in serum leptin levels (-48.4%, p < 0.001) was observed after intervention without changes in total peptide YY and insulin levels.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615652", "endSection": "sections.0" }, { "offsetInBeginSection": 1576, "offsetInEndSection": 1765, "text": "ur data suggest that the control of spontaneous physical activity by gut hormones or their neuropeptide targets may represent an important mechanistic component of energy balance regulation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554896", "endSection": "sections.0" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1165, "text": "Hunger and gut hormones remained unchanged during the bed rest.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20061436", "endSection": "sections.0" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1309, "text": "weight-bearing exercise has a greater exercise-induced appetite suppressive effect compared with non-weight-bearing exercise, and both forms of exercise lowered acylated ghrelin and increased total PYY, but the changes did not differ significantly between exercise modes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23402716", "endSection": "sections.0" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1211, "text": "Appetite (P\u00a0<\u00a00.0005) and acylated ghrelin (P\u00a0<\u00a00.002) were suppressed during exercise but more so during SIE. Peptide YY increased during exercise but most consistently during END (P\u00a0<\u00a00.05). Acylated ghrelin was lowest in the afternoon of SIE (P\u00a0=\u00a00.018) despite elevated appetite", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23111564", "endSection": "sections.0" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1791, "text": "Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21927572", "endSection": "sections.0" }, { "offsetInBeginSection": 810, "offsetInEndSection": 926, "text": "Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19158129", "endSection": "sections.0" }, { "offsetInBeginSection": 1370, "offsetInEndSection": 1457, "text": "These findings suggest ghrelin and PYY may regulate appetite during and after exercise,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18987287", "endSection": "sections.0" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1125, "text": "significant (P < 0.05) interaction effects for hunger, acylated ghrelin, and PYY, indicating suppressed hunger and acylated ghrelin during aerobic and resistance exercise and increased PYY during aerobic exercise", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18987287", "endSection": "sections.0" }, { "offsetInBeginSection": 1682, "offsetInEndSection": 1774, "text": "'exercise-induced anorexia' may potentially be linked to increased PYY, GLP-1 and PP levels.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17470516", "endSection": "sections.0" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1393, "text": "Hunger scores and PYY, GLP-1 and PP levels showed an inverse temporal pattern during the 1-h exercise/control intervention", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17470516", "endSection": "sections.0" }, { "offsetInBeginSection": 744, "offsetInEndSection": 969, "text": "Exercise significantly increased mean PYY, GLP-1 and PP levels, and this effect was maintained during the post-exercise period for GLP-1 and PP. No significant effect of exercise was observed on postprandial levels of ghrelin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17470516", "endSection": "sections.0" }, { "offsetInBeginSection": 2370, "offsetInEndSection": 2469, "text": "following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11321513", "endSection": "sections.0" }, { "offsetInBeginSection": 1977, "offsetInEndSection": 2362, "text": "We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11321513", "endSection": "sections.0" }, { "offsetInBeginSection": 729, "offsetInEndSection": 811, "text": "the unrestricted exercise group has a significantly elevated SRIF-LI concentration", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2888163", "endSection": "sections.0" }, { "offsetInBeginSection": 360, "offsetInEndSection": 440, "text": "Exercise has recently been reported to influence ghrelin and PYY concentrations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20690071", "endSection": "sections.0" } ] }, { "body": "What are the effects of depleting protein km23-1 (DYNLRB1) in a cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15925487", "http://www.ncbi.nlm.nih.gov/pubmed/19711352", "http://www.ncbi.nlm.nih.gov/pubmed/17420258", "http://www.ncbi.nlm.nih.gov/pubmed/22637579", "http://www.ncbi.nlm.nih.gov/pubmed/23079622", "http://www.ncbi.nlm.nih.gov/pubmed/16778097", "http://www.ncbi.nlm.nih.gov/pubmed/19571232" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_41324156523900B", "o": "http://linkedlifedata.com/resource/#_41324156523900A" } ], "ideal_answer": [ "The knockdown of km23-1 results in numerous effects at the cellular level, such as decreased cell migration. Additionaly, km23-1 is involved in signalling pathways and its knockdown results in decreased RhoA activation, inhibition of TGF\u03b2-mediated activation of ERK and JNK, phosphorylation of c-Jun, transactivation of the c-Jun promoter and decreased TGFbeta responses." ], "exact_answer": [ [ "inhibition of cell migration of human colon carcinoma cells (HCCCs) in wound-healing assays" ], [ "decreased RhoA activation" ], [ "inhibition of TGF\u03b2-mediated activation of ERK and JNK" ], [ "phosphorylation of c-Jun" ], [ "transactivation of the c-Jun promoter" ], [ "decreased key TGFbeta responses" ] ], "concepts": [ "http://www.uniprot.org/uniprot/DLRB1_HUMAN" ], "type": "list", "id": "515a7ffdd24251bc050000a5", "snippets": [ { "offsetInBeginSection": 797, "offsetInEndSection": 1156, "text": "Finally, our results demonstrated for the first time that depletion of km23-1 inhibited cell migration of human colon carcinoma cells (HCCCs) in wound-healing assays. Overall, our findings demonstrate that km23-1 regulates RhoA and motility-associated actin modulating proteins, suggesting that km23-1 may represent a novel target for anti-metastatic therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23079622", "endSection": "sections.0" }, { "offsetInBeginSection": 650, "offsetInEndSection": 798, "text": "Further, knockdown of km23-1 inhibited TGF\u03b2-mediated activation of ERK and JNK, phosphorylation of c-Jun, and transactivation of the c-Jun promoter.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22637579", "endSection": "sections.0" }, { "offsetInBeginSection": 719, "offsetInEndSection": 795, "text": "knockdown (KD) of km23-1 decreased RhoA activation in Mv1Lu epithelial cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23079622", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "We have previously reported that the dynein light chain (DLC) km23-1 is required for Smad2-dependent TGFbeta signaling.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19711352", "endSection": "sections.0" }, { "offsetInBeginSection": 701, "offsetInEndSection": 894, "text": "Blockade of km23-1 using a small interfering RNA approach resulted in a reduction in both total intracellular Smad2 levels and in nuclear levels of phosphorylated Smad2 after TGFbeta treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17420258", "endSection": "sections.0" }, { "offsetInBeginSection": 572, "offsetInEndSection": 741, "text": "Blockade of km23 using small interfering RNAs significantly decreased key TGFbeta responses, including induction of fibronectin expression and inhibition of cell growth.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15925487", "endSection": "sections.0" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1446, "text": "On the other hand, inhibiting the endogenous DYNLRB1 with gene-specific small interfering RNA or pharmacologically with a specific inhibitor (vanadate) led to a significant (P < 0.05) decrease in folate uptake.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571232", "endSection": "sections.0" }, { "offsetInBeginSection": 189, "offsetInEndSection": 361, "text": "Functional studies showed that some mutations disrupt km23 function, resulting in aberrant transforming growth factor-beta signaling and presumably enhanced tumorigenicity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16778097", "endSection": "sections.0" } ] }, { "body": "Treatment of which disease was investigated in the MR CLEAN study?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25179366", "http://www.ncbi.nlm.nih.gov/pubmed/25432979", "http://www.ncbi.nlm.nih.gov/pubmed/25517348", "http://www.ncbi.nlm.nih.gov/pubmed/24330796" ], "ideal_answer": [ "Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study investigated endovascular treatment for acute ischemic stroke." ], "exact_answer": [ "acute ischemic stroke" ], "type": "factoid", "id": "54cf7051f693c3b16b000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "INTRODUCTION: A recent randomized controlled trial (RCT), the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), demonstrated better outcomes with endovascular treatment compared with medical therapy for acute ischemic stroke (AIS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25432979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "INTRODUCTION: A recent randomized controlled trial (RCT), the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), demonstrated better outcomes with endovascular treatment compared with medical therapy for acute ischemic stroke (AIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25432979", "endSection": "abstract" }, { "offsetInBeginSection": 1845, "offsetInEndSection": 2223, "text": "CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25517348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "MR CLEAN, a multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands: study protocol for a randomized controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25179366", "endSection": "title" }, { "offsetInBeginSection": 480, "offsetInEndSection": 744, "text": " In our view, a rational and ethical approach would now be to treat quickly with IV rtPA and when possible, refer and include in new randomized clinical trials that compare intra-arterial treatment with standard care, such as MR CLEAN or BASICS in the Netherlands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24330796", "endSection": "abstract" } ] }, { "body": "Which factors activate zygotic gene expression during the maternal-to-zygotic transition in zebrafish?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24056933" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0134867", "o": "D015027" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2030872", "o": "D015027" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0062415", "o": "D015870" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0057285", "o": "D015870" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0057283", "o": "D015870" } ], "ideal_answer": [ "Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression." ], "exact_answer": [ [ "Nanog" ], [ "Pou5f1" ], [ "SoxB1" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015027", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018507", "http://amigo.geneontology.org/amigo/term/GO:0010468", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020869", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005786", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870" ], "type": "list", "id": "56a92be0a17756b72f000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056933", "endSection": "title" }, { "offsetInBeginSection": 889, "offsetInEndSection": 1088, "text": "Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056933", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 487, "text": "Here we show that Nanog, Pou5f1 (also called Oct4) and SoxB1 regulate zygotic gene activation in zebrafish.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056933", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 618, "text": "Here we show that Nanog, Pou5f1 (also called Oct4) and SoxB1 regulate zygotic gene activation in zebrafish. We identified several hundred genes directly activated by maternal factors, constituting the first wave of zygotic transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056933", "endSection": "abstract" } ] }, { "body": "Is irritable bowel syndrome more common in women with endometriosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15341718", "http://www.ncbi.nlm.nih.gov/pubmed/18478547", "http://www.ncbi.nlm.nih.gov/pubmed/14501624", "http://www.ncbi.nlm.nih.gov/pubmed/15605531", "http://www.ncbi.nlm.nih.gov/pubmed/22134016", "http://www.ncbi.nlm.nih.gov/pubmed/22096721", "http://www.ncbi.nlm.nih.gov/pubmed/18646315", "http://www.ncbi.nlm.nih.gov/pubmed/21868492", "http://www.ncbi.nlm.nih.gov/pubmed/23507008", "http://www.ncbi.nlm.nih.gov/pubmed/15894210", "http://www.ncbi.nlm.nih.gov/pubmed/19694698", "http://www.ncbi.nlm.nih.gov/pubmed/18715239", "http://www.ncbi.nlm.nih.gov/pubmed/17635599", "http://www.ncbi.nlm.nih.gov/pubmed/17701798", "http://www.ncbi.nlm.nih.gov/pubmed/19832874", "http://www.ncbi.nlm.nih.gov/pubmed/17493437", "http://www.ncbi.nlm.nih.gov/pubmed/21527837", "http://www.ncbi.nlm.nih.gov/pubmed/18715240" ], "ideal_answer": [ "Yes, irritable bowel syndrome (IBS) is more common in women with endometriosis. It has been shown that 15% of the patients with endometriosis also had IBS. Women with endometriosis are more likely to have received a diagnosis of IBS. Endometriosis may coexist with or be misdiagnosed as IBS." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:289", "http://www.disease-ontology.org/api/metadata/DOID:9778" ], "type": "yesno", "id": "54f08d4a94afd61504000016", "snippets": [ { "offsetInBeginSection": 1673, "offsetInEndSection": 1799, "text": "CONCLUSIONS: Comorbid pain syndromes, mood conditions and asthma are common in adolescents and young women with endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23507008", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 753, "text": "There are many etiologies of pelvic pain that present with symptoms resembling those of endometriosis-associated pelvic pain that are not diagnosable with laparoscopy, such as interstitial cystitis and irritable bowel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134016", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 399, "text": "Often, such patients are labelled with irritable bowel syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22096721", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 417, "text": "Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21868492", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1220, "text": "RESULTS: Compared with controls, patients with minimal to mild and moderate to severe endometriosis had a higher prevalence of symptoms consistent with IBS (0% vs 65% and 50%, respectively, p<0.001) with significantly lower mean pain thresholds (39.5 mm\u2002Hg (95% CI 36.0 to 43.0) vs 28.1 mm\u2002Hg (95% CI 24.5 to 31.6), p=0.001 and 28.8 mm\u2002Hg (95% CI 24.9 to 32.6), p=0.002) not explained by differences in rectal compliance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21868492", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1176, "text": "Similarly, women with a history of irritable bowel syndrome were twice as likely to develop endometriosis [AOR=1.9, 95% CI (1.03-3.87)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527837", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1638, "text": "A weak association between reported family history of endometriosis and history of irritable bowel syndrome and the development of endometriosis was also observed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Irritable bowel syndrome and chronic constipation in patients with endometriosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19832874", "endSection": "title" }, { "offsetInBeginSection": 718, "offsetInEndSection": 866, "text": "Fifteen per cent of the patients with endometriosis also had IBS and 14% of the patients with endometriosis had functional constipation without IBS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19832874", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1211, "text": "CONCLUSION: In patients with endometriosis, 29% also had IBS or constipation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19832874", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 966, "text": "Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19694698", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 1304, "text": "Compared with controls, women with endometriosis had increased risks of abdominopelvic pain (OR 5.2 [95% CI: 4.7-5.7]), dysmenorrhoea (OR 8.1 [95% CI: 7.2-9.3]), menorrhagia (OR 4.0 [95% CI: 3.5-4.5]), subfertility (OR 8.2 [95% CI: 6.9-9.9]), dyspareunia and/or postcoital bleeding (OR 6.8 [95% CI: 5.7-8.2]), and ovarian cysts (OR 7.3 [95% CI: 5.7-9.4]), and of being diagnosed with irritable bowel syndrome (IBS) (OR 1.6 [95% CI: 1.3-1.8]) or pelvic inflammatory disease (OR 3.0 [95% CI: 2.5-3.6]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18715240", "endSection": "abstract" }, { "offsetInBeginSection": 1585, "offsetInEndSection": 1673, "text": "Endometriosis may coexist with or be misdiagnosed as pelvic inflammatory disease or IBS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18715240", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1285, "text": "RESULTS: Compared with the controls, women with endometriosis were 3.5 times more likely to have received a diagnosis of IBS (OR 3.5 [95% CI: 3.1-3.9]). Even after women had been diagnosed with endometriosis, they were still two and a half times more likely to receive a new diagnosis of IBS when compared with the controls (OR 2.5 [95% CI: 2.2-2.8]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18715239", "endSection": "abstract" }, { "offsetInBeginSection": 1513, "offsetInEndSection": 1683, "text": "CONCLUSIONS: Women with endometriosis are more likely to be diagnosed with IBS and PID than controls, even after a definitive diagnosis of endometriosis has been reached.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18715239", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "In women, clinical studies suggest that functional pain syndromes such as irritable bowel syndrome, interstitial cystitis, and fibromyalgia, are co-morbid with endometriosis, chronic pelvic pain, and others diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18646315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "In women, clinical studies suggest that pain syndromes such as irritable bowel syndrome and interstitial cystitis, which are associated with visceral hyperalgesia, are often comorbid with endometriosis and chronic pelvic pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18478547", "endSection": "abstract" }, { "offsetInBeginSection": 1721, "offsetInEndSection": 1823, "text": "Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine with EM group than in controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17635599", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 596, "text": "Intestinal endometriosis can mimic many gastrointestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, infections and neoplasms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17493437", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 790, "text": "Endometriosis is often associated with other painful conditions such as irritable bowel syndrome, interstitial cystitis and fibromyalgia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15894210", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 1057, "text": "CONCLUSIONS: Diagnosis of endometriosis should be considered in women with recurrent monthly abdominal pain and bowel symptoms, especially if accompanied by gynaecologic complaints, even because the significant symptoms overlap with the irritable bowel syndrome (IBS) and makes the differentiation extremely difficult.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15605531", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 452, "text": "Intestinal endometriosis is typically asymptomatic; however, when symptoms occur, they can mimic those of irritable bowel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15341718", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1085, "text": " Similarly, women with a history of irritable bowel syndrome were twice as likely to develop endometriosis [AOR=1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527837", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 416, "text": "Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21868492", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 405, "text": "Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21868492", "endSection": "abstract" } ] }, { "body": "What is evaluated using the EORTC QLQ \u2013 INFO25 questionnaire?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21680301", "http://www.ncbi.nlm.nih.gov/pubmed/24834120", "http://www.ncbi.nlm.nih.gov/pubmed/25475735", "http://www.ncbi.nlm.nih.gov/pubmed/21671697", "http://www.ncbi.nlm.nih.gov/pubmed/22052786", "http://www.ncbi.nlm.nih.gov/pubmed/20674333", "http://www.ncbi.nlm.nih.gov/pubmed/22638756" ], "ideal_answer": [ "The European Organisation for Research and Treatment of Cancer Quality of Life Group information questionnaire (EORTC QLQ-INFO 25) evaluates the level of information patients have received in different areas of their disease, treatment and care, and evaluates qualitative aspects together with satisfaction with information." ], "type": "summary", "id": "54f49995d0d681a040000002", "snippets": [ { "offsetInBeginSection": 688, "offsetInEndSection": 788, "text": "The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22638756", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 342, "text": "METHODS: The EORTC information questionnaire, EORTC QLQ-INFO25, was administered during the treatment process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22052786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The EORTC information questionnaire, EORTC QLQ-INFO25. Validation study for Spanish patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680301", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "INTRODUCTION: The EORTC QLQ-INFO25 evaluates the information received by cancer patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Information disclosure to cancer patients: EORTC QLQ-INFO25 questionnaire.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21671697", "endSection": "title" }, { "offsetInBeginSection": 568, "offsetInEndSection": 986, "text": "We highlight the need to assess patients' characteristics and desires through questionnaires and interviews and present the European Organisation for Research and Treatment of Cancer Quality of Life Group information questionnaire (EORTC QLQ-INFO 25). This instrument evaluates the level of information patients have received in different areas of their disease, treatment and care, and evaluates qualitative aspects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21671697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "AIM: The EORTC Quality of Life (QOL) Group has developed an instrument to evaluate the information received by cancer patients. This study assessed the psychometric characteristics of the EORTC INFO module in a large international/multi-cultural sample of cancer patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20674333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "An international validation study of the EORTC QLQ-INFO25 questionnaire: an instrument to assess the information given to cancer patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20674333", "endSection": "title" }, { "offsetInBeginSection": 688, "offsetInEndSection": 787, "text": "The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22638756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "The EORTC QLQ-INFO25 evaluates the information received by cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680301", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 786, "text": "The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22638756", "endSection": "abstract" } ] }, { "body": "Does BNP increase after intensive exercise in athletes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16338248", "http://www.ncbi.nlm.nih.gov/pubmed/16446686", "http://www.ncbi.nlm.nih.gov/pubmed/16125505", "http://www.ncbi.nlm.nih.gov/pubmed/17289431", "http://www.ncbi.nlm.nih.gov/pubmed/19092706", "http://www.ncbi.nlm.nih.gov/pubmed/12417808", "http://www.ncbi.nlm.nih.gov/pubmed/16879068", "http://www.ncbi.nlm.nih.gov/pubmed/17395308", "http://www.ncbi.nlm.nih.gov/pubmed/11320362", "http://www.ncbi.nlm.nih.gov/pubmed/12890912", "http://www.ncbi.nlm.nih.gov/pubmed/23304255", "http://www.ncbi.nlm.nih.gov/pubmed/18630737", "http://www.ncbi.nlm.nih.gov/pubmed/19638823", "http://www.ncbi.nlm.nih.gov/pubmed/18248532", "http://www.ncbi.nlm.nih.gov/pubmed/18184752", "http://www.ncbi.nlm.nih.gov/pubmed/14523304", "http://www.ncbi.nlm.nih.gov/pubmed/22653984", "http://www.ncbi.nlm.nih.gov/pubmed/18076361" ], "ideal_answer": [ "BNP and NTproBNP increase early after exercise in healthy athletes performing different types of sports. It is unknown the reason of this increase. The transient increases in BNP, NT-pro-BNP and troponin T are more likely to reflect myocardial stunning than cardiomyocyte damage." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054874", "http://www.uniprot.org/uniprot/ANFB_OREMO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020097", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177" ], "type": "yesno", "id": "531d2aa5267d7dd053000003", "snippets": [ { "offsetInBeginSection": 1235, "offsetInEndSection": 1368, "text": "NT-pro-BNP was significantly elevated postexercise in both adults and adolescents and remained above baseline at 24 h in both groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22653984", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1427, "text": "NT-pro-BNP concentrations increased significantly (28 +/- 17.1 vs 795 +/- 823 ng x L, P < 0.05), whereas postrace cTnT were elevated in just five athletes (20%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19092706", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 902, "text": "[NT-pro-BNP] was observed immediately after the marathon (median [NT-pro-BNP] before: 39.6 pg ml(-1), after: 138.6 pg ml(-1), p=0.003) with a further increase on day one. [BNP] did not increase immediately after the marathon but increased on day one (median [BNP] before: 15 pg ml(-1), day one: 27.35 pg ml(-1), p=0.006).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18630737", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 896, "text": "Pro-BNP was significantly increased immediately post-race (27+/-21 vs 7+/-2 pmol/L pre-race, P < or = 0.007), which 12-24 h later, decreased to 19+/-14 pmol/L (P = 0.07 vs pre-race).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18248532", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1520, "text": "The relatively high NT-proBNP levels after active recovery when psychophysical stress is higher, because of cycling and cold water immersion, suggest that not only endurance exercise, but also strenuous, stressful short exercise can induce an increase in NT-proBNP concentrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18076361", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1418, "text": "Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16879068", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1843, "text": "Increases in NT-proBNP can be found in a major part of obviously healthy athletes after prolonged strenuous exercise. The release of BNP during and after exercise may not result from myocardial damage but may have cytoprotective and growth-regulating effects. The different nature of exercise-induced increases in BNP and cardiac troponins has to be elucidated in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16338248", "endSection": "abstract" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1175, "text": "In healthy cyclists, transient increases in NT-pro-BNP and cTnT are more likely to reflect cardiac fatigue than injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16125505", "endSection": "abstract" }, { "offsetInBeginSection": 1670, "offsetInEndSection": 1777, "text": "The rise in BNP in older athletes may reflect a reversible, mainly diastolic left ventricular dysfunction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14523304", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 918, "text": "Plasma BNP concentrations were higher in both the judo and marathon groups than in controls, and positively correlated with LV mass as well as with deceleration time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12890912", "endSection": "abstract" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1593, "text": "Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11320362", "endSection": "abstract" } ] }, { "body": "What is the association of estrogen replacement therapy and intracranial meningioma risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16570277", "http://www.ncbi.nlm.nih.gov/pubmed/22287638", "http://www.ncbi.nlm.nih.gov/pubmed/21067422", "http://www.ncbi.nlm.nih.gov/pubmed/20802020", "http://www.ncbi.nlm.nih.gov/pubmed/15006250", "http://www.ncbi.nlm.nih.gov/pubmed/24138870", "http://www.ncbi.nlm.nih.gov/pubmed/20738039", "http://www.ncbi.nlm.nih.gov/pubmed/20091865", "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "http://www.ncbi.nlm.nih.gov/pubmed/25335165" ], "ideal_answer": [ "The association between hormone replacement therapy and meningioma risk is controversial. Increased risk of meningioma was demonstrated in estrogen-only hormonal replacement therapy. However, other studies did not find an association between hormonal replacement therapy and meningioma risk." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015914", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579", "http://www.disease-ontology.org/api/metadata/DOID:3565" ], "type": "summary", "id": "56bf3a79ef6e39474100000f", "snippets": [ { "offsetInBeginSection": 1178, "offsetInEndSection": 1814, "text": "The meta-analyses yielded significantly increased risks for all CNS tumors, glioma and meningioma in users of estrogen-only [1.35 (1.22-1.49), 1.23 (1.06-1.42) and 1.31 (1.20-1.43), respectively] but not estrogen-progestin HT [1.09 (0.99-1.19), 0.92 (0.78-1.08) and 1.05 (0.95-1.16), respectively]; these differences were statistically significant (p<0.005 for each tumor type). There was no significant difference between glioma and meningioma risk in users of estrogen-only HT. The totality of the available evidence suggests an increased risk of all CNS tumors (and of glioma and meningioma separately) in users of estrogen-only HT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25335165", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1310, "text": "Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "endSection": "abstract" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1838, "text": "The relationship between current use of exogenous hormones and meningioma remains unclear, limited by the small numbers of patients currently on oral hormone medications and a lack of hormone receptor data for meningioma tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 1052, "text": "Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P<0.001) than in the background population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287638", "endSection": "abstract" }, { "offsetInBeginSection": 1291, "offsetInEndSection": 1375, "text": "Estradiol-only therapy was accompanied with a slightly increased risk of meningioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287638", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 447, "text": "Results from several prospective, large-scale studies indicate that postmenopausal hormone therapy may increase the risk for diagnosing meningioma by 30-80%, but there is no effect in regard to glioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21067422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "A retrospective study including more than 350,000 women, about 1400 of whom had developed meningioma, showed that the risk of meningioma was about twice as high in users of postmenopausal hormone replacement therapy as in non-users.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20738039", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 870, "text": "Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05-1.36), 1.09 (95% CI: 0.89-1.32), 1.34 (95% CI: 1.03-1.75) and 1.58 (95% CI: 1.02-2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20091865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND: Previous studies on association of exogenous female sex hormones and risk for meningioma have yielded conflicting results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "endSection": "abstract" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1131, "text": "RESULTS: Postmenopausal hormonal treatment, use of contraceptives, or fertility treatment did not influence the risk of meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "endSection": "abstract" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1549, "text": "CONCLUSIONS: Overall, we found little indication that reproductive factors or use of exogenous sex hormones affect meningioma risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 954, "text": "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND: The role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 812, "text": "RESULTS: Although risk of meningioma appeared modestly elevated in past OC users (OR = 1.5, 95% CI 0.8 - 2.7), and in current users (OR = 2.5, 95% CI 0.5 - 12.6), the confidence intervals were wide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1073, "text": "Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI 0.4 - 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 - 2.2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract" }, { "offsetInBeginSection": 1318, "offsetInEndSection": 1716, "text": " Overall, in post menopausal women, HRT use appeared to confer a non-significant protective effect, and was not associated with low or high PR expressing meningiomas.CONCLUSION: This study found little evidence of associations between meningioma and exogenous hormone exposures in women but did suggest that some hormonal exposures may influence tumor biology in those women who develop meningioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1608, "text": "The increased odds ratios with African Americans was retained in post-menopausal women, while the protective odds ratios for pregnancy, smoking and oral contraceptives (OCs) became stronger in pre-menopausal women. The pattern by duration and timing of use does not suggest an etiologic role for OCs or hormone replacement therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16570277", "endSection": "abstract" }, { "offsetInBeginSection": 1044, "offsetInEndSection": 1221, "text": "The use of hormone replacement therapy in symptomatic postmenopausal women either with previously treated disease or with dormant tumors is discussed, but remains controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006250", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1088, "text": "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1321, "text": "OC use was associated with increased risk of a meningioma expressing less rather than more PR (OR = 3.2, 95% CI 1.3 - 8.0). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1421, "text": "In further analysis by hormone receptor status, there was some indication for an increased risk of progesterone receptor-positive meningiomas associated with oral contraceptive use (OR 1.39, 95% confidence interval 0.92-2.10) and other hormonal contraception (OR 1.50, 95% CI 0.95-2.36). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138870", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 954, "text": "available data suggest an association between the use of hormone replacement therapy and increased meningioma risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 1296, "text": "A significant positive association existed between meningioma risk and increased body mass index (p < 0.01) while a significant negative association existed between meningioma risk and current smoking (p < 0.01). Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1068, "text": "A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20802020", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1379, "text": "Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67). There was no association between use of fertility medications and meningioma risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 954, "text": "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1120, "text": "A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20802020", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1296, "text": "Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "endSection": "abstract" } ] }, { "body": "Are there web based self management strategies for chronic pain ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23859438", "http://www.ncbi.nlm.nih.gov/pubmed/24251273", "http://www.ncbi.nlm.nih.gov/pubmed/23768119", "http://www.ncbi.nlm.nih.gov/pubmed/23538392", "http://www.ncbi.nlm.nih.gov/pubmed/24067267" ], "ideal_answer": [ "Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. ", "Yes, there are successful web based self management strategies for chronic pain." ], "exact_answer": "yes", "type": "yesno", "id": "54fefff26ad7dcbc1200000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Fibromyalgia Symptom Reduction by Online Behavioral Self-monitoring, ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251273", "endSection": "title" }, { "offsetInBeginSection": 368, "offsetInEndSection": 565, "text": "This study aimed to evaluate effects of a web-based, self-monitoring and symptom management system (SMARTLog) that analyzes personal self-monitoring data and delivers data-based feedback over time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251273", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1374, "text": "Moderate use (3 times weekly x 3 months) increased likelihood of clinically significant improvements in pain, memory, gastrointestinal problems, depression, fatigue, and concentration; heavy use (4.5 times weekly x five months) produced the above plus improvement in stiffness and sleep difficulties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251273", "endSection": "abstract" }, { "offsetInBeginSection": 2365, "offsetInEndSection": 2576, "text": "Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24067267", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1653, "text": "Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859438", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 499, "text": "Patient involvement can be fostered by web-based applications combining health information with decision support or behaviour change support. These so-called Interactive Health Communication Applications (IHCAs) can reach great numbers of patients at low financial cost and provide information and support at the time, place and learning speed patients prefer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23768119", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 502, "text": "Web-based interventions may also be effective in enhancing self-management for individuals with chronic pain, but little is known about long-term effects. Research on Web-based interventions to support self-management following participation in pain management programs is limited. OBJECTIVE: The aim is to examine the long-term effects of a 4-week smartphone-intervention ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538392", "endSection": "abstract" } ] }, { "body": "Is Weaver syndrome similar to Sotos?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9781911", "http://www.ncbi.nlm.nih.gov/pubmed/12464997", "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "http://www.ncbi.nlm.nih.gov/pubmed/22287508", "http://www.ncbi.nlm.nih.gov/pubmed/12807965", "http://www.ncbi.nlm.nih.gov/pubmed/19011474", "http://www.ncbi.nlm.nih.gov/pubmed/24852293", "http://www.ncbi.nlm.nih.gov/pubmed/24214728" ], "ideal_answer": [ "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling." ], "exact_answer": "yes", "type": "yesno", "id": "571f34ac0fd6f91b68000005", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 439, "text": "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24852293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling: NSD1 preferentially methylates lysine residue 36 of histone 3 (H3K36) and is primarily associated with active transcription, while EZH2 shows specificity for lysine residue 27 (H3K27) and is associated with transcriptional repression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 966, "text": "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011474", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 700, "text": "Thus, it is not surprising that prenatal overgrowth occurs in several syndromes, including the Sotos and Weaver syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9781911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12464997", "endSection": "title" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1159, "text": "We conclude therefore that NSD1 mutations account for most cases of Sotos syndrome and a significant number of Weaver syndrome cases in our series.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12807965", "endSection": "abstract" }, { "offsetInBeginSection": 1794, "offsetInEndSection": 1979, "text": "We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12464997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12464997", "endSection": "title" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1805, "text": "We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12464997", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1226, "text": "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 1143, "offsetInEndSection": 1411, "text": "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": " Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia. Two previous cases of neuroblastoma have been reported in children with Weaver syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011474", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 66, "text": "Weaver syndrome is closely related to Sotos syndrome,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011474", "endSection": "abstract" }, { "offsetInBeginSection": 1143, "offsetInEndSection": 1226, "text": "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287508", "endSection": "abstract" } ] }, { "body": "Which enzyme is targeted by Evolocumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24691094", "http://www.ncbi.nlm.nih.gov/pubmed/25410046", "http://www.ncbi.nlm.nih.gov/pubmed/25052769", "http://www.ncbi.nlm.nih.gov/pubmed/24661068", "http://www.ncbi.nlm.nih.gov/pubmed/24477778", "http://www.ncbi.nlm.nih.gov/pubmed/25079474", "http://www.ncbi.nlm.nih.gov/pubmed/24662398", "http://www.ncbi.nlm.nih.gov/pubmed/25470376", "http://www.ncbi.nlm.nih.gov/pubmed/24694531", "http://www.ncbi.nlm.nih.gov/pubmed/24961142", "http://www.ncbi.nlm.nih.gov/pubmed/24481874", "http://www.ncbi.nlm.nih.gov/pubmed/24373748", "http://www.ncbi.nlm.nih.gov/pubmed/25282520", "http://www.ncbi.nlm.nih.gov/pubmed/24953393", "http://www.ncbi.nlm.nih.gov/pubmed/24953396", "http://www.ncbi.nlm.nih.gov/pubmed/25002170", "http://www.ncbi.nlm.nih.gov/pubmed/24859266", "http://www.ncbi.nlm.nih.gov/pubmed/24678979", "http://www.ncbi.nlm.nih.gov/pubmed/25282519", "http://www.ncbi.nlm.nih.gov/pubmed/24255061", "http://www.ncbi.nlm.nih.gov/pubmed/24509273", "http://www.ncbi.nlm.nih.gov/pubmed/24284914", "http://www.ncbi.nlm.nih.gov/pubmed/24598985", "http://www.ncbi.nlm.nih.gov/pubmed/24825642" ], "ideal_answer": [ "Evolocumab (AMG145) is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that demonstrated marked reductions in plasma low-density lipoprotein cholesterol concentrations in statin-intolerant patients." ], "exact_answer": [ "proprotein convertase subtilisin/kexin type 9" ], "type": "factoid", "id": "54e0d1491388e8454a000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Efficacy and safety profile of evolocumab (AMG145), an injectable inhibitor of the proprotein convertase subtilisin/kexin type 9: the available clinical evidence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661068", "endSection": "title" }, { "offsetInBeginSection": 353, "offsetInEndSection": 582, "text": "AREAS COVERED: Evolocumab (AMG145) is a monoclonal antibody inhibiting the proprotein convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal recycling by targeting it for degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661068", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598985", "endSection": "title" }, { "offsetInBeginSection": 449, "offsetInEndSection": 560, "text": "We report a pooled analysis from four phase 2 studies of evolocumab (AMG 145), a monoclonal antibody to PCSK9. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24509273", "endSection": "title" }, { "offsetInBeginSection": 449, "offsetInEndSection": 775, "text": "METHODS: A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab, a fully human monoclonal antibody to PCSK9, on Lp(a), the relationship between Lp(a) and lowering of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B, and the influence of background statin therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24509273", "endSection": "abstract" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 1597, "text": "CONCLUSIONS: Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in Lp(a). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24509273", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 703, "text": "Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, including evolocumab (previously AMG 145), dramatically lowered LDL-C in phase 2 clinical trials when administered alone or in combination with a statin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24481874", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 722, "text": "Evolocumab (AMG 145) is a fully human monoclonal antibody that binds PCSK9, inhibiting its interaction with the LDL receptor to preserve LDL-receptor recycling and reduce LDL-C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24477778", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 1082, "text": "Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24284914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND: Evolocumab (AMG 145), a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) in phase 2 studies of 12 weeks' duration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255061", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 876, "text": "These compounds act either by reducing low-density lipoprotein (LDL) production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen) or by inhibiting microsomal triglyceride transfer protein (lomitapide), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9) (evolocumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25410046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25282520", "endSection": "title" }, { "offsetInBeginSection": 292, "offsetInEndSection": 433, "text": "Evolocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), reduced LDL cholesterol by 16% in a pilot study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25282520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25282519", "endSection": "title" }, { "offsetInBeginSection": 346, "offsetInEndSection": 470, "text": "We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25282519", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1099, "text": "Some of the anti-dyslipidemic drugs which work by PCSK9 inhibition include evolocumab, alirocumab and ALN-PCS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079474", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 842, "text": "We highlight the different steps of this adventure and review the published clinical trials especially those with the anti-PCSK9 antibodies evolocumab (AMG 145) and alirocumab (SAR236553/REGN727), which are in phase III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25052769", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 930, "text": "Monoclonal antibodies against PCSK9 represent so far the most advanced approach in clinical development, with alirocumab, evolocumab and bococizumab under advanced clinical development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25002170", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 554, "text": "AREAS COVERED: Evolocumab and alirocumab are fully human monoclonal antibodies inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) that binds to hepatic LDL receptor and prevents it from normal recycling by targeting it for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24961142", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 939, "text": "Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show that PCSK9 inhibitors are equally well tolerated, with adverse events mainly limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and back pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24961142", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1208, "text": "Four classes of newer lipid-lowering drugs offer promising advances in treating FH, namely the apolipoprotein-B synthesis inhibitors (mipomersen), the microsomal transfer protein inhibitors (lomitapide), the cholesterol ester transfer protein inhibitors (anacetrapib, evacetrapib) and the proprotein convertase subtilisin/kexin type 9 inhibitors (evolocumab, alirocumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24953396", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 762, "text": "Monoclonal antibodies that inhibit proprotein convertase subtilisin/ kexin type 9 (PCSK9), which degrades the LDL receptor, like alirocumab and evolocumab, are in phase 3 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24953393", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 462, "text": "In support of the drug development program for Evolocumab, a fully human IgG\u2082 antibody that targets PCSK9, a quantitative ELISA to measure free PCSK9 in human serum was developed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "IMPORTANCE: In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24694531", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 580, "text": "Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24694531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24691094", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 342, "text": "BACKGROUND: Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24691094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "BACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in hypercholesterolemic, statin-treated Japanese patients at high cardiovascular risk--primary results from the phase 2 YUKAWA study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24662398", "endSection": "title" } ] }, { "body": "Are ultraconserved elements often transcribed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "http://www.ncbi.nlm.nih.gov/pubmed/22094949", "http://www.ncbi.nlm.nih.gov/pubmed/20202189", "http://www.ncbi.nlm.nih.gov/pubmed/22617881", "http://www.ncbi.nlm.nih.gov/pubmed/24384562", "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "http://www.ncbi.nlm.nih.gov/pubmed/19660540", "http://www.ncbi.nlm.nih.gov/pubmed/21187392", "http://www.ncbi.nlm.nih.gov/pubmed/16705037", "http://www.ncbi.nlm.nih.gov/pubmed/23393190" ], "ideal_answer": [ "Yes. Especially, a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand." ], "exact_answer": "yes", "type": "yesno", "id": "553a8d78f321868558000003", "snippets": [ { "offsetInBeginSection": 222, "offsetInEndSection": 479, "text": "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1476, "text": "Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393190", "endSection": "title" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1303, "text": "The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as 'Olfactores conserved non-coding elements'", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393190", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 1083, "text": "We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20202189", "endSection": "abstract" }, { "offsetInBeginSection": 1506, "offsetInEndSection": 1876, "text": "Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20202189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19660540", "endSection": "title" }, { "offsetInBeginSection": 360, "offsetInEndSection": 564, "text": "The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22617881", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 555, "text": "Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22094949", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1232, "text": "The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393190", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 320, "text": "Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393190", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16705037", "endSection": "title" }, { "offsetInBeginSection": 484, "offsetInEndSection": 630, "text": "In this report, we show that the Dlx-5/6 ultraconserved region is transcribed to generate an alternatively spliced form of Evf-1, the ncRNA Evf-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16705037", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1738, "text": "These studies identify a critical role for TUC338 in regulation of transformed cell growth and of transcribed ultraconserved ncRNA as a unique class of genes involved in the pathobiology of HCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187392", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 426, "text": "Transcribed ultraconserved region (T-UCR) transcripts are a novel class of lncRNAs transcribed from ultraconserved regions (UCRs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24384562", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1231, "text": "The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393190", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 307, "text": "Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 554, "text": "Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22094949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Transcribed ultraconserved region in human cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24384562", "endSection": "title" }, { "offsetInBeginSection": 730, "offsetInEndSection": 859, "text": "We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20202189", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1265, "text": "Although uc.338 is partially located within the poly(rC) binding protein 2 (PCBP2) gene, the transcribed ncRNA encoding uc.338 is expressed independently of PCBP2 and was cloned as a 590-bp RNA gene, termed TUC338", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187392", "endSection": "abstract" }, { "offsetInBeginSection": 1624, "offsetInEndSection": 1846, "text": "Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20202189", "endSection": "abstract" } ] }, { "body": "What is the methyl donor of DNA (cytosine-5)-methyltransferases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7578083", "http://www.ncbi.nlm.nih.gov/pubmed/8441638", "http://www.ncbi.nlm.nih.gov/pubmed/1584813", "http://www.ncbi.nlm.nih.gov/pubmed/11208790", "http://www.ncbi.nlm.nih.gov/pubmed/8065896", "http://www.ncbi.nlm.nih.gov/pubmed/15273274", "http://www.ncbi.nlm.nih.gov/pubmed/7607467" ], "ideal_answer": [ "S-adenosyl-L-methionine (AdoMet, SAM) is the methyl donor of DNA (cytosine-5)-methyltransferases. DNA (cytosine-5)-methyltransferases catalyze the transfer of a methyl group from S-adenosyl-L-methionine to the C-5 position of cytosine residues in DNA." ], "exact_answer": [ "S-adenosyl-L-methionine" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003886" ], "type": "factoid", "id": "51404dd723fec90375000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "The product of the dcm gene is the only DNA cytosine-C5 methyltransferase of Escherichia coli K-12; it catalyses transfer of a methyl group from S-adenosyl methionine (SAM) to the C-5 position of the inner cytosine residue of the cognate sequence CCA/TGG. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8441638", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Deoxycytosine methylase (Dcm) enzyme activity causes mutagenesis in vitro either directly by enzyme-induced deamination of cytosine to uracil in the absence of the methyl donor, S-adenosylmethionine (SAM), or indirectly through spontaneous deamination of [5-methyl]cytosine to thymine", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11208790", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "In the absence of DNA substrate, the DNA methyltransferase (MTase) M.BspRI can methylate itself using the methyl donor S-adenosyl-L-methionine (AdoMet). The methyl group is transferred to two Cys residues of the MTase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7607467", "endSection": "sections.0" }, { "offsetInBeginSection": 446, "offsetInEndSection": 539, "text": "The reaction is fairly insensitive to the methyl donor in the reaction, S-adenosylmethionine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7578083", "endSection": "sections.0" }, { "offsetInBeginSection": 641, "offsetInEndSection": 831, "text": "Formation of the complex was dependent upon the presence of the methyl donor S-adenosylmethionine, suggesting that it comprises an enzyme-linked 5-substituted dihydrocytosine moiety in DNA. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1584813", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The DNA (cytosine-5)-methyltransferase (m5C-MTase) M.BspRI is able to accept the methyl group from the methyl donor S-adenosyl-L-methionine (AdoMet) in the absence of DNA. Transfer of the methyl group to the enzyme is a slow reaction relative to DNA methylation. S", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8065896", "endSection": "sections.0" }, { "offsetInBeginSection": 170, "offsetInEndSection": 374, "text": "Here, we report the structure of HhaI methyltransferase in complex with DNA containing a south-constrained abasic carbocyclic sugar at the target site in the presence of the methyl donor byproduct AdoHcy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15273274", "endSection": "sections.0" } ] }, { "body": "Is peripheral neuroepithelioma related to Ewing sarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8204006", "http://www.ncbi.nlm.nih.gov/pubmed/25303625", "http://www.ncbi.nlm.nih.gov/pubmed/9825003", "http://www.ncbi.nlm.nih.gov/pubmed/7595741", "http://www.ncbi.nlm.nih.gov/pubmed/7513503", "http://www.ncbi.nlm.nih.gov/pubmed/1283315", "http://www.ncbi.nlm.nih.gov/pubmed/10968707", "http://www.ncbi.nlm.nih.gov/pubmed/8321753", "http://www.ncbi.nlm.nih.gov/pubmed/3390826", "http://www.ncbi.nlm.nih.gov/pubmed/8644855", "http://www.ncbi.nlm.nih.gov/pubmed/7771924", "http://www.ncbi.nlm.nih.gov/pubmed/3760036" ], "ideal_answer": [ "Experimental data support the concept that Ewing sarcoma and peripheral neuroepithelioma are both peripheral primitive neuroectodermal neoplasms, differing only in the extent of neuroectodermal phenotype and morphological differentiation." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3369", "http://www.disease-ontology.org/api/metadata/DOID:3368", "http://www.disease-ontology.org/api/metadata/DOID:4388", "http://www.disease-ontology.org/api/metadata/DOID:4389", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018241", "http://www.disease-ontology.org/api/metadata/DOID:4980", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512" ], "type": "yesno", "id": "552fa6f5bc4f83e828000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 784, "text": "The term \"small round-cell tumor\" describes a group of highly aggressive malignant tumors composed of relatively small and monotonous undifferentiated cells with high nuclear to cytoplasmic ratios. This group includes Ewing's sarcoma (ES), peripheral neuroepithelioma (aka, primitive neuroectodermal tumor or extraskeletal ES), peripheral neuroblastoma (\"classic-type\"), rhabdomyosarcoma, desmoplastic small round-cell tumor, lymphoma, leukemia, small-cell osteosarcoma, small-cell carcinoma (either undifferentiated or neuroendocrine), olfactory neuroblastoma, cutaneous neuroendocrine carcinoma (aka, Merkel-cell carcinoma), small-cell melanoma, and mesenchymal chondrosarcoma. Their clinical presentations often overlap, thus making a definitive diagnosis problematic in some cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10968707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "AIMS: To retrospectively study the DNA content in a series of childhood Ewing Family Tumors (EFT), and to investigate its prognostic value. METHODS: The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraosseous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9825003", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 172, "text": "To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7595741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "Large group of small-round-cell tumours of soft tissues and bone represents a complex diagnostic problem for the pathologists. Neuronal nature of many tumours from this group is proven by means of new methods--immunophenotypic analysis, tissue culture, cytogenetics. Peripheral neuroepithelioma, Ewing tumour, primitive neuroectodermal tumour (PNET), Askin tumour belong to these neoplasms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7771924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Comparison of Ewing's sarcoma of bone and peripheral neuroepithelioma. An immunocytochemical and ultrastructural analysis of two primitive neuroectodermal neoplasms", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8204006", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 415, "text": "Ewing's sarcoma of bone (ESB) and peripheral neuroepithelioma (PN) are frequently considered to be different tumors. Some researchers have suggested that PN is morphologically a neuroectodermal Ewing's sarcoma. We sought to determine the extent of neuroectodermal features in conventional ESB on direct patient material (25 cases) and to compare these tumors with a similar group of readily diagnosed PNs (10 cases)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8204006", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 827, "text": "Neuroectodermal antigens (neuron-specific enolase, Leu-7 [HNK-1], neurofilament 200 kd, and S100) were found in nine of 10 cases of PN and in 17 of 25 cases of ESB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8204006", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1265, "text": "These data support the concept that ESB and PN are both peripheral primitive neuroectodermal neoplasms, differing only in extent of neuroectodermal phenotype and morphological differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8204006", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1291, "text": "Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3760036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Ewings sarcoma (ES) and peripheral neuroepithelioma (PN) are closely related tumors, and it can be difficult to distinguish them from other small-round-cell tumors (SRCTs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7513503", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1123, "text": "The presence of this translocation in Ewing sarcoma and peripheral primitive neuroectodermal tumor has been taken as evidence that these two tumors are related.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8644855", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1299, "text": "Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3760036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Indistinguishable patterns of protooncogene expression in two distinct but closely related tumors: Ewing's sarcoma and neuroepithelioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3390826", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1283315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET) are a group of small round cell sarcomas that show varying degrees of neuroectodermal differentiation characterized by translocation involving the EWS gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are closely related tumors, and it can be difficult to distinguish them from other small-round-cell tumors (SRCTs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7513503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1283315", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 754, "text": "This genetical similarity further supports a nosological concept according to which Askin's tumour, Ewing's sarcoma and peripheral neuroepithelioma represent phenotypic variations of the same tumour, namely the peripheral primitive neuroectodermal tumour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8321753", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1298, "text": "Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3760036", "endSection": "abstract" } ] }, { "body": "Which signaling pathway does sonidegib inhibit?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24598114", "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "http://www.ncbi.nlm.nih.gov/pubmed/24523439", "http://www.ncbi.nlm.nih.gov/pubmed/24613036", "http://www.ncbi.nlm.nih.gov/pubmed/25646180", "http://www.ncbi.nlm.nih.gov/pubmed/24817600", "http://www.ncbi.nlm.nih.gov/pubmed/24928708", "http://www.ncbi.nlm.nih.gov/pubmed/25473003" ], "ideal_answer": [ "Sonidegib is a Hedghog signalling pathway inhibitor." ], "exact_answer": [ "Hedghog signalling pathway" ], "type": "factoid", "id": "56d0451c3975bb303a00000e", "snippets": [ { "offsetInBeginSection": 942, "offsetInEndSection": 1066, "text": "The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25473003", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 129, "text": "Distinct molecular subgroups of medulloblastoma, including hedgehog (Hh) pathway-activated disease, have been reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25473003", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 296, "text": "We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 989, "text": "Among such pathways, RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, EGFR, and Notch are of particular interest because agents that selectively inhibit these pathways are available and can be readily combined with agents such as vismodegib, sonidegib (LDE225), and BMS-833923, which target smoothened-a key Hh pathway regulator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24613036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24817600", "endSection": "abstract" }, { "offsetInBeginSection": 1598, "offsetInEndSection": 1830, "text": "Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598114", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 412, "text": "We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 378, "text": "We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.METHODS: BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 646, "text": "PURPOSE: This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Oral sonidegib was administered to 103 patients with advanced solid tumors, including medulloblastoma and basal cell carcinoma (BCC), at doses ranging from 100 to 3,000 mg daily and 250 to 750 mg twice daily, continuously, with a single-dose pharmacokinetics run-in period. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "PURPOSE: The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24817600", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 520, "text": "Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.METHODS: BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients had locally advanced basal cell carcinoma not amenable to curative surgery or radiation or metastatic basal cell carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "PURPOSE: The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. METHODS: Six subjects received a single oral dose of 800 mg \u00b9\u2074C-sonidegib (74 kBq, 2.0 \u00b5Ci) under fasting conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24817600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": " The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. Six subjects received a single oral dose of 800 mg \u00b9\u2074C-sonidegib (74 kBq, 2.0 \u00b5Ci) under fasting conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24817600", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1611, "text": "Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598114", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1039, "text": "The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25473003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 617, "text": " This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. Oral sonidegib was administered to 103 patients with advanced solid tumors, including medulloblastoma and basal cell carcinoma (BCC), at doses ranging from 100 to 3,000 mg daily and 250 to 750 mg twice daily, continuously, with a single-dose pharmacokinetics run-in period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523439", "endSection": "abstract" }, { "offsetInBeginSection": 1203, "offsetInEndSection": 1608, "text": "Preliminary clinical data also suggest that inhibition of the Hh pathway, alone or in combination with JAK2 inhibition, may enable disease modification in patients with MF. Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. Six subjects received a single oral dose of 800 mg \u00b9\u2074C-sonidegib (74 kBq, 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24817600", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1486, "text": "including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 617, "text": "This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. Oral sonidegib was administered to 103 patients with advanced solid tumors, including medulloblastoma and basal cell carcinoma (BCC), at doses ranging from 100 to 3,000 mg daily and 250 to 750 mg twice daily, continuously, with a single-dose pharmacokinetics run-in period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523439", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 285, "text": "Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "endSection": "abstract" } ] }, { "body": "In which phase of the cell cycle arrest is impaired in Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11035915", "http://www.ncbi.nlm.nih.gov/pubmed/9414295", "http://www.ncbi.nlm.nih.gov/pubmed/14988723", "http://www.ncbi.nlm.nih.gov/pubmed/9650445", "http://www.ncbi.nlm.nih.gov/pubmed/11749045" ], "ideal_answer": [ "In response to damage induced by DNA cross-linking agents, the S-phase checkpoint is inefficient in Fanconi anemia (FA) cells, leading to accumulation of secondary lesions, such as single- and double-strand breaks and gaps. The prolonged time in G2 phase seen in FA cells therefore exists in order to allow the cells to remove lesions which accumulated during the preceding abnormal S phase." ], "exact_answer": [ "In Fanconi anemia cells, the S-phase checkpoint is inefficient." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007050", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059447", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0022403" ], "type": "factoid", "id": "54ede8c594afd61504000009", "snippets": [ { "offsetInBeginSection": 538, "offsetInEndSection": 850, "text": "We found that ICLs activate a branched pathway downstream of the ATR kinase: one branch depending on CHK1 activity and the other on the FANCs-RMN complex. The transient slow-down of DNA synthesis was abolished in cells lacking ATR, whereas CHK1-siRNA-treated cells, NBS1 or FA cells showed partial S-phase arrest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14988723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Arrest of S-phase progression is impaired in Fanconi anemia cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11035915", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability, hypersensitivity to DNA cross-linking agents, and a prolonged G2 phase of the cell cycle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11035915", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 374, "text": "We observed a marked dose-dependent accumulation of FA cells in the G2 compartment after treatment with 4,5',8-trimethylpsoralen (Me(3)Pso) in combination with 365 nm irradiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11035915", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 1090, "text": "Taken together, the above data suggest that, in response to damage induced by DNA cross-linking agents, the S-phase checkpoint is inefficient in FA cells. This would lead to accumulation of secondary lesions, such as single- and double-strand breaks and gaps. The prolonged time in G2 phase seen in FA cells therefore exists in order to allow the cells to remove lesions which accumulated during the preceding abnormal S phase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11035915", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Fanconi anemia (FA) is a genetic disorder defined by cellular hypersensitivity to DNA cross-linking agents, such as mitomycin C (MMC). MMC causes increased FA cell death, chromosome breakage, and accumulation in the G2 phase of the cell cycle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9650445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "DNA cross-linker-induced G2/M arrest in group C Fanconi anemia lymphoblasts reflects normal checkpoint function", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9414295", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Cells from individuals with Fanconi anemia (FA) arrest excessively in the G2/M cell cycle compartment after exposure to low doses of DNA cross-linking agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9414295", "endSection": "abstract" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1871, "text": "Based on these studies we conclude that the aberrant G2/M arrest that typifies the response of FA(C) cells to low doses of cross-linking agents does not represent an abnormal cell cycle response but instead represents a normal cellular response to the excessive DNA damage that results in FA(C) cells following exposure to low doses of cross-linking agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9414295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Arrest of S-phase progression is impaired in Fanconi anemia cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11035915", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11749045", "endSection": "title" } ] }, { "body": "Which DNA sequences are more prone for the formation of R-loops?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16793409", "http://www.ncbi.nlm.nih.gov/pubmed/25147206", "http://www.ncbi.nlm.nih.gov/pubmed/24843019", "http://www.ncbi.nlm.nih.gov/pubmed/20080737", "http://www.ncbi.nlm.nih.gov/pubmed/15531884", "http://www.ncbi.nlm.nih.gov/pubmed/18986989", "http://www.ncbi.nlm.nih.gov/pubmed/24743386", "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "http://www.ncbi.nlm.nih.gov/pubmed/22464440", "http://www.ncbi.nlm.nih.gov/pubmed/24787137", "http://www.ncbi.nlm.nih.gov/pubmed/25296254" ], "ideal_answer": [ "R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia. Physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes. R-loops are particularly enriched over G-rich terminator elements." ], "exact_answer": [ [ "G-rich elements" ], [ "CpG islands" ], [ "(CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n" ] ], "type": "list", "id": "56c3327c50c68dd41600000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25147206", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1429, "text": "Double-R-loop formation and processing to instability was extended to the expanded C9orf72 (GGGGCC)\u00b7(GGCCCC) repeats, known to cause amyotrophic lateral sclerosis and frontotemporal dementia, providing the first suggestion through which these repeats may become unstable. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25147206", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 461, "text": "Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 466, "text": "R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25296254", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 576, "text": "Furthermore, we have previously shown that R-loops are particularly enriched over G-rich terminator elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25296254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "R-loops associated with triplet repeat expansions", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24787137", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Periodic DNA patrolling underlies diverse functions of Pif1 on R-loops and G-rich DNA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24843019", "endSection": "title" }, { "offsetInBeginSection": 33, "offsetInEndSection": 233, "text": "Ginno et al. (2012) describe unusual sequence features at promoter CpG islands that can lead to formation of persistent RNA-DNA hybrids (R loops), which are proposed to prevent genomic DNA methylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22464440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "R loops stimulate genetic instability of CTG.CAG repeats", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080737", "endSection": "title" }, { "offsetInBeginSection": 179, "offsetInEndSection": 333, "text": " We demonstrate, using biochemical and genetic approaches, that the formation of stable RNA.DNA hybrids enhances the instability of CTG.CAG repeat tracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080737", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 265, "text": " The R-loop, previously characterized in vitro at the leading strand replication origin (OH), is isolated as a native RNA-DNA hybrid copurifying with mtDNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18986989", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 475, "text": "All of these R-loops arise upon generation of a G-rich RNA strand by an RNA polymerase upon transcription of a C-rich DNA template strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16793409", "endSection": "abstract" }, { "offsetInBeginSection": 1219, "offsetInEndSection": 1525, "text": "Finally, non-denaturing bisulfite mapping of the displaced single-stranded DNA confirmed R-loop formation at the endogenous FMR1 locus and further indicated that R-loops formed over CGG repeats may be prone to structural complexities, including hairpin formation, not commonly associated with other R-loops", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743386", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 754, "text": "We have observed that transcription through the GC-rich FMR1 5'UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743386", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 440, "text": "which is rich in AT and not prone to form R-loops,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15531884", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1527, "text": "Finally, non-denaturing bisulfite mapping of the displaced single-stranded DNA confirmed R-loop formation at the endogenous FMR1 locus and further indicated that R-loops formed over CGG repeats may be prone to structural complexities, including hairpin formation, not commonly associated with other R-loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743386", "endSection": "abstract" } ] }, { "body": "Mutation of which gene is implicated in the familial isolated pituitary adenoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23743763", "http://www.ncbi.nlm.nih.gov/pubmed/24078436", "http://www.ncbi.nlm.nih.gov/pubmed/24050928", "http://www.ncbi.nlm.nih.gov/pubmed/24423289", "http://www.ncbi.nlm.nih.gov/pubmed/22915287", "http://www.ncbi.nlm.nih.gov/pubmed/17961654", "http://www.ncbi.nlm.nih.gov/pubmed/22291433", "http://www.ncbi.nlm.nih.gov/pubmed/17244780", "http://www.ncbi.nlm.nih.gov/pubmed/21450940", "http://www.ncbi.nlm.nih.gov/pubmed/23038625", "http://www.ncbi.nlm.nih.gov/pubmed/23652674", "http://www.ncbi.nlm.nih.gov/pubmed/21778740", "http://www.ncbi.nlm.nih.gov/pubmed/17893250", "http://www.ncbi.nlm.nih.gov/pubmed/19883897", "http://www.ncbi.nlm.nih.gov/pubmed/21454441", "http://www.ncbi.nlm.nih.gov/pubmed/24996936", "http://www.ncbi.nlm.nih.gov/pubmed/20570174", "http://www.ncbi.nlm.nih.gov/pubmed/20457215", "http://www.ncbi.nlm.nih.gov/pubmed/23371967", "http://www.ncbi.nlm.nih.gov/pubmed/22584704", "http://www.ncbi.nlm.nih.gov/pubmed/21498161", "http://www.ncbi.nlm.nih.gov/pubmed/20669561", "http://www.ncbi.nlm.nih.gov/pubmed/20616502", "http://www.ncbi.nlm.nih.gov/pubmed/22527616", "http://www.ncbi.nlm.nih.gov/pubmed/24366639", "http://www.ncbi.nlm.nih.gov/pubmed/20616498", "http://www.ncbi.nlm.nih.gov/pubmed/20833337", "http://www.ncbi.nlm.nih.gov/pubmed/23310926", "http://www.ncbi.nlm.nih.gov/pubmed/24789813", "http://www.ncbi.nlm.nih.gov/pubmed/23633209", "http://www.ncbi.nlm.nih.gov/pubmed/23286415", "http://www.ncbi.nlm.nih.gov/pubmed/17993773", "http://www.ncbi.nlm.nih.gov/pubmed/20506337" ], "ideal_answer": [ "Mutation of aryl hydrocarbon receptor interacting protein (AIP) gene was implicated in the familial isolated pituitary adenoma (FIPA) syndrome. About 20% of the families with FIPA harbor inactivating mutation in AIP gene." ], "exact_answer": [ "aryl hydrocarbon receptor interacting protein" ], "type": "factoid", "id": "551c23bc6b348bb82c00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a high percentage of cases, but the AIP gene plays an important role in the etiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Familial isolated pituitary adenoma caused by a Aip gene mutation not described before in a family context.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078436", "endSection": "title" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1014, "text": "We report a Spanish family with FIPA in whom a mutation in the AIP gene previously unreported in a familiar context was identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078436", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 1068, "text": "FIPA, an autosomal-dominant disease with variable penetrance, is explained in 20% of patients by germline mutations in the tumor suppressor aryl hydrocarbon receptor interacting protein(AIP), while no gene abnormality has been identified to date in the majority of the FIPA families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652674", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1486, "text": "Understanding the tumorigenic process in AIP-positive and AIP-negative FIPA patients could result in better diagnostic and treatment options for both familial and sporadic cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652674", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 230, "text": "The aryl hydrocarbon receptor interacting protein (AIP) gene has a major role in the pathogenesis of familial isolated pituitary adenoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633209", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 581, "text": " The discovery of heterozygous, loss-of-function germline mutations in the gene encoding the aryl hydrocarbon receptor interacting protein (AIP) in 2006 has subsequently enabled the identification of a mutation in this gene in 20% of FIPA families and 20% of childhood-onset simplex soma- totroph adenomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23310926", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 977, "text": " This review aims to summarize currently available clinical data on AIP mutation-positive and negative FIPA patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23310926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "[Aryl hydrocarbon receptor interacting protein gene and familial isolated pituitary adenomas].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286415", "endSection": "title" }, { "offsetInBeginSection": 337, "offsetInEndSection": 424, "text": "Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Germline mutations of aryl-hydrocarbon-receptor interacting protein (AIP) are associated with pituitary adenoma predisposition. They occur in 20\u00a0% of familial isolated pituitary adenoma (FIPA) and in about 3-5\u00a0% of sporadic pituitary adenomas, especially in early onset somatotropinomas and prolactinomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22915287", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1188, "text": "We report a FIPA family harbouring an AIP R16H change, supporting the hypothesis that the latter represents a variant of unknown significance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22915287", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 805, "text": "Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22584704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Genetic analysis in a patient presenting with meningioma and familial isolated pituitary adenoma (FIPA) reveals selective involvement of the R81X mutation of the AIP gene in the pathogenesis of the pituitary tumor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22527616", "endSection": "title" }, { "offsetInBeginSection": 305, "offsetInEndSection": 633, "text": "About 20 % of the families with FIPA harbor inactivating mutation in aryl hydrocarbon receptor-interacting protein gene (AIP) associated with loss of heterozygosity of the same genetic locus (11q13) in the tumor. Rarely different types of extra-pituitary tumors have been described in the setting of AIP mutation-positive FIPA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22527616", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 197, "text": "Mutations in AIP account only for 15-25% of FIPA families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22291433", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 559, "text": "In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498161", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Germline mutations in the aryl hydrocarbon receptor-interacting protein gene (AIP) predispose to young-onset pituitary tumours, most often to GH- or prolactin-secreting adenomas, and most of these patients belong to familial isolated pituitary adenoma families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21454441", "endSection": "abstract" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1628, "text": "We also briefly describe the genetic basis of three other inherited states predisposing individuals to endocrine tumors, namely Carney's syndrome, hyperparathyroidism type 2 (HRPT2) and familial isolated pituitary adenoma (FIPA), which are related to inactivating mutations in the PRKAR1-alpha, HRPT2 and AIP genes, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20669561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The identification of mutations in the Aryl hydrocarbon receptor interacting protein (AIP) gene in a subset of familial isolated pituitary adenoma (FIPA) cases has recently expanded our understanding of the pathophysiology of inherited pituitary adenoma disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616498", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 655, "text": "Several studies and reviews have assessed the genetic and clinical features of AIP-mutated FIPA patients, which range from a complete lack of symptoms in adult/elderly individuals to large, aggressive early-onset pituitary tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616498", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 538, "text": "In 20% of FIPA families, heterozygous mutations have been described in the aryl hydrocarbon receptor interacting (AIP) gene, whereas in other families the causative gene(s) are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20570174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "A novel C-terminal nonsense mutation, Q315X, of the aryl hydrocarbon receptor-interacting protein gene in a Japanese familial isolated pituitary adenoma family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789813", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371967", "endSection": "title" }, { "offsetInBeginSection": 659, "offsetInEndSection": 804, "text": "Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22584704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21450940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Clinical experience in the screening and management of a large kindred with familial isolated pituitary adenoma due to an aryl hydrocarbon receptor interacting protein (AIP) mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24423289", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma kindreds.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22291433", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Although the cause of familial isolated pituitary adenoma (FIPA) remains unknown in many cases, germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene were identified in approximately 20 % of families with FIPA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a high percentage of cases, but the AIP gene plays an important role in the etiology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078436", "endSection": "abstract" }, { "offsetInBeginSection": 784, "offsetInEndSection": 1066, "text": "FIPA, an autosomal-dominant disease with variable penetrance, is explained in 20% of patients by germline mutations in the tumor suppressor aryl hydrocarbon receptor interacting protein(AIP), while no gene abnormality has been identified to date in the majority of the FIPA families", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652674", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 803, "text": "Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22584704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "The identification of mutations in the Aryl hydrocarbon receptor interacting protein (AIP) gene in a subset of familial isolated pituitary adenoma (FIPA) cases has recently expanded our understanding of the pathophysiology of inherited pituitary adenoma disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616498", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 1111, "text": "To date, the number of molecular genetic factors unequivocally linked to pituitary tumours can be counted on the fingers of one hand: (1) GNAS1 activation in acromegaly; (2) the MENIN and p27Kip1 (CDKN1B) mutations associated with multiple endocrine neoplasia type 1; (3) mutations of PRKA1RA with loss of 17q22-24 in Carney complex, and (4) aryl hydrocarbon receptor interacting protein gene mutations in 15% of familial isolated pituitary adenomas and 50% of familial isolated acromegaly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21778740", "endSection": "abstract" } ] }, { "body": "which mutations of troponin C gene have been found to cause hypertrophic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19439414", "http://www.ncbi.nlm.nih.gov/pubmed/18572189", "http://www.ncbi.nlm.nih.gov/pubmed/23425245", "http://www.ncbi.nlm.nih.gov/pubmed/21262074", "http://www.ncbi.nlm.nih.gov/pubmed/22489623", "http://www.ncbi.nlm.nih.gov/pubmed/16302972", "http://www.ncbi.nlm.nih.gov/pubmed/20459070", "http://www.ncbi.nlm.nih.gov/pubmed/18285522", "http://www.ncbi.nlm.nih.gov/pubmed/22815480", "http://www.ncbi.nlm.nih.gov/pubmed/19506933", "http://www.ncbi.nlm.nih.gov/pubmed/24260207", "http://www.ncbi.nlm.nih.gov/pubmed/20566645" ], "ideal_answer": [ "The following mutations of troponin C gene have been found to cause hypertrophic cardiomyopathy: L29Q; A8V; A31S; E134D; c.363dupG; A23Q; D145E and C84Y" ], "exact_answer": [ [ "L29Q" ], [ "A8V" ], [ "A31S" ], [ "E134D" ], [ "c.363dupG" ], [ "A23Q" ], [ "D145E" ], [ "C84Y" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019209", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "list", "id": "5314a7a4dae131f847000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The Ca(2+) binding properties of the FHC-associated cardiac troponin C (cTnC) mutation L29Q were examined in isolated cTnC, troponin complexes, reconstituted thin filament preparations, and skinned cardiomyocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Effects of calcium binding and the hypertrophic cardiomyopathy A8V mutation on the dynamic equilibrium between closed and open conformations of the regulatory N-domain of isolated cardiac troponin C", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23425245", "endSection": "title" }, { "offsetInBeginSection": 1489, "offsetInEndSection": 1644, "text": "We also used PRE data to assess the structural effects of a familial hypertrophic cardiomyopathy point mutation located within the N-domain of cTnC (A8V). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23425245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "A mutation in TNNC1-encoded cardiac troponin C, TNNC1-A31S, predisposes to hypertrophic cardiomyopathy and ventricular fibrillation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815480", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 471, "text": "Here, we report clinical and functional characterization of a novel TNNC1 mutation, A31S, identified in a pediatric HCM proband with multiple episodes of ventricular fibrillation and aborted sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815480", "endSection": "abstract" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1758, "text": "In summary, we report a novel mutation in the TNNC1 gene that is associated with HCM pathogenesis and may predispose to the pathogenesis of a fatal arrhythmogenic subtype of HCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "The objective of this work was to investigate the effect of hypertrophic cardiomyopathy-linked A8V and E134D mutations in cardiac troponin C (cTnC) on the response of reconstituted thin filaments to calcium upon phosphorylation of cardiac troponin I (cTnI) by protein kinase A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22489623", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 418, "text": "We describe a novel type of mutation (c.363dupG) in Troponin C, a rare form of hypertrophic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21262074", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 1030, "text": "We report the first frameshift mutation (c.363dupG or p.Gln122AlafsX30) in Troponin C causing hypertrophic cardiomyopathy (and sudden cardiac death) in a 19-year-old male, and have demonstrated that the mutation segregates with hypertrophic cardiomyopathy within the family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21262074", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 716, "text": "One mutant (A23Q) was found with HCM-like properties (increased Ca(2+) sensitivity of force and normal levels of ATPase inhibition).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20566645", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 285, "text": "In this study, we investigated the effects of hypertrophic cardiomyopathy-linked mutations A8V, E134D, and D145E in cardiac troponin C on the properties of the C-domain sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Recently four new hypertrophic cardiomyopathy mutations in cardiac troponin C (cTnC) (A8V, C84Y, E134D, and D145E) were reported, and their effects on the Ca(2+) sensitivity of force development were evaluated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19439414", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 987, "text": "Comprehensive open reading frame/splice site mutation analysis of TNNC1 performed on 1025 unrelated HCM patients enrolled over the last 10 years revealed novel missense mutations in TNNC1: A8V, C84Y, E134D, and D145E.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18572189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The cardiac troponin C (cTnC) mutation, L29Q, has been found in a patient with familial hypertrophic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285522", "endSection": "abstract" }, { "offsetInBeginSection": 1666, "offsetInEndSection": 1858, "text": "These results demonstrate that the L29Q mutation enhances the Ca(2+)-binding characteristics of cTnC and that when incorporated into cardiac myocytes, this mutant alters myocyte contractility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the transduction of the protein kinase A dependent phosphorylation signal from cardiac troponin I to C.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16302972", "endSection": "title" }, { "offsetInBeginSection": 304, "offsetInEndSection": 422, "text": "This mutation leads to a leucine-glutamine exchange at position 29 in the nonfunctional calcium-binding site of cTnC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16302972", "endSection": "abstract" } ] }, { "body": "What is known about the effect of acupuncture in smoking cessation ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24030452", "http://www.ncbi.nlm.nih.gov/pubmed/17264832", "http://www.ncbi.nlm.nih.gov/pubmed/15861492", "http://www.ncbi.nlm.nih.gov/pubmed/16566674", "http://www.ncbi.nlm.nih.gov/pubmed/17698433", "http://www.ncbi.nlm.nih.gov/pubmed/22373002", "http://www.ncbi.nlm.nih.gov/pubmed/11154059", "http://www.ncbi.nlm.nih.gov/pubmed/10024707", "http://www.ncbi.nlm.nih.gov/pubmed/12356614", "http://www.ncbi.nlm.nih.gov/pubmed/15004442", "http://www.ncbi.nlm.nih.gov/pubmed/18405159", "http://www.ncbi.nlm.nih.gov/pubmed/12416359" ], "ideal_answer": [ "Ear acupressure (EAP) and ear acupuncture have been used for smoking cessation, and some positive results have been reported.\nAuricular (ear) acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant.\nThe combined acupuncture-education group showing the greatest effect from treatment." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026881", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020831", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012907", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016540", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015669" ], "type": "summary", "id": "535d78137d100faa09000005", "snippets": [ { "offsetInBeginSection": 256, "offsetInEndSection": 380, "text": "Ear acupressure (EAP) and ear acupuncture have been used for smoking cessation, and some positive results have been reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24030452", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 295, "text": "Auricular (ear) acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22373002", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 842, "text": "Acupuncture combined with auricular point sticking and pressing has reliable therapeutic effect for smoking cessation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18405159", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 307, "text": "Acupuncture has been promoted as a treatment modality for smoking cessation. However, its efficacy still remains controversial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17698433", "endSection": "abstract" }, { "offsetInBeginSection": 1857, "offsetInEndSection": 2168, "text": "Our results showed that auricular acupuncture did not have a better efficacy in smoking cessation compared to sham acupuncture. Combined acupuncture with behavior counseling or with nicotine replacement therapy should be used in further smoking cessation trials to enhance the success rate of smoking cessation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17698433", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 958, "text": "Combining ten studies showed auricular acupuncture at 'correct' points to be more effective than control interventions, odds ratio 2.24 (95% CI 1.61, 3.10),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17264832", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1532, "text": "Auricular acupuncture appears to be effective for smoking cessation, but the effect may not depend on point location.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17264832", "endSection": "abstract" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1263, "text": "The combination of auricular acupressure and Internet-assisted smoking cessation program was more efficacious than auricular acupressure alone in terms of quit rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16566674", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1579, "text": "auricular acupuncture in smoking cessation has some effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15861492", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1750, "text": "With a one-year success rate of 41.1% ear acupuncture is a competitive alternative to orthodox medicine withdrawal methods. Acupuncture treatment can be applied and adapted individually, furthermore it is economical and without side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15004442", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 513, "text": "Auriculotherapy is an useful aid for giving up smoking. It is easy and painless, has no secondary effects and it is economic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12416359", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 462, "text": "the combined acupuncture-education group showing the greatest effect from treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12356614", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1042, "text": "Acupuncture and education, alone and in combination, significantly reduce smoking; however, combined they show a significantly greater effect, as seen in subjects with a greater pack-year history.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12356614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "A double blind, randomized, placebo-controlled clinical study was conducted to evaluate the efficacy of laser acupuncture treatment in adolescent smokers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154059", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 780, "text": "Thus, there was no significant difference in the rates of smoking cessation in the treatment and control groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154059", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1101, "text": "This simple ear electroacupuncture treatment was significantly more effective in helping volunteers to quit smoking than placebo treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10024707", "endSection": "abstract" } ] }, { "body": "Which post-translational histone modifications are characteristic of constitutive heterochromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11740497", "http://www.ncbi.nlm.nih.gov/pubmed/21541345", "http://www.ncbi.nlm.nih.gov/pubmed/17710556", "http://www.ncbi.nlm.nih.gov/pubmed/11356363", "http://www.ncbi.nlm.nih.gov/pubmed/22319459", "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "http://www.ncbi.nlm.nih.gov/pubmed/18592385", "http://www.ncbi.nlm.nih.gov/pubmed/18987983", "http://www.ncbi.nlm.nih.gov/pubmed/17891782", "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "http://www.ncbi.nlm.nih.gov/pubmed/12581305", "http://www.ncbi.nlm.nih.gov/pubmed/20532208" ], "ideal_answer": [ "H3K9me3 is the major marker of constitutive heterochromatin. Other histone methylation marks usually found in constitutive heterochromatin, are H4K20me3 and H3K79me3. Classical histone modifications associated with heterochromatin include H3K9me2, H3K27me1 and H3K27me2. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin. H3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage" ], "exact_answer": [ [ "H3S10p" ], [ "H3K36me3" ], [ "H4K20me3" ], [ "H3K9me3" ], [ "H3K79me3" ], [ "H3K9me2" ], [ "H3K27me1" ], [ "H3K27me2" ], [ "H3K27me3" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006570", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002843" ], "type": "list", "id": "56c6dd275795f9a73e000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "H3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "endSection": "title" }, { "offsetInBeginSection": 393, "offsetInEndSection": 665, "text": "We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1382, "text": "This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 624, "text": "Classical histone modifications associated with heterochromatin, including H3K9me2, H3K27me1 and H3K27me2, were distributed throughout both A and B chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18987983", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 813, "text": "In this review, available data will be evaluated concerning (1) the phylogenetic distribution of H3K9me as heterochromatin-specific histone modification and its evolutionary stability in relation to other epigenetic marks, (2) known families of H3K9 methyltransferases, (3) their responsibility for the formation of constitutive heterochromatin and (4) the evolution of Su(var)3-9-like and SUVH-like H3K9 methyltransferases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17710556", "endSection": "abstract" }, { "offsetInBeginSection": 1436, "offsetInEndSection": 1748, "text": " While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription in spite of the simultaneous presence of activating marks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20532208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Histone modifications in Arabidopsis- high methylation of H3 lysine 9 is dispensable for constitutive heterochromatin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581305", "endSection": "title" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1056, "text": "The recent discovery of the first histone Lys methyltransferase has allowed the identification of a molecular mechanism in which the specific methylation of histone H3 at Lys9 generates a binding site for heterochromatin-associated proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11356363", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1086, "text": "At the SUMO-1 labelled areas, the presence of HP1alpha protein, as well as of trimethylated H3-K9 and H4-K20 histone modifications, supports a role for SUMO-1 in constitutive heterochromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18592385", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1612, "text": "Surprisingly, the marsupial Xi was stably enriched for modifications associated with constitutive heterochromatin in all eukaryotes (H4K20me3, H3K9me3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21541345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Constitutive heterochromatin during mouse oogenesis: the pattern of histone H3 modifications and localization of HP1alpha and HP1beta proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17891782", "endSection": "title" }, { "offsetInBeginSection": 109, "offsetInEndSection": 266, "text": "In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22319459", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 393, "text": "Methylation of histone H3 at lysine 9 (H3-Lys9) by site-specific histone methyltransferases (Suv39h HMTases) marks constitutive heterochromatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11740497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "H3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "endSection": "title" }, { "offsetInBeginSection": 163, "offsetInEndSection": 338, "text": "In placental mammals non-coding XIST RNA triggers silencing of one X (Xi) and recruits a characteristic suite of epigenetic modifications, including the histone mark H3K27me3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21541345", "endSection": "abstract" } ] }, { "body": "GV1001 vaccine targets which enzyme?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24815142", "http://www.ncbi.nlm.nih.gov/pubmed/19072345", "http://www.ncbi.nlm.nih.gov/pubmed/20822343", "http://www.ncbi.nlm.nih.gov/pubmed/21377838", "http://www.ncbi.nlm.nih.gov/pubmed/19388882", "http://www.ncbi.nlm.nih.gov/pubmed/23827187", "http://www.ncbi.nlm.nih.gov/pubmed/24954781", "http://www.ncbi.nlm.nih.gov/pubmed/22841437", "http://www.ncbi.nlm.nih.gov/pubmed/21586625", "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "http://www.ncbi.nlm.nih.gov/pubmed/24411674" ], "ideal_answer": [ "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence. It has been developed as a vaccine against various cancers." ], "exact_answer": [ "human telomerase reverse transcriptase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014612", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798" ], "type": "factoid", "id": "56c1f02cef6e39474100004c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24411674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "endSection": "title" }, { "offsetInBeginSection": 120, "offsetInEndSection": 365, "text": "A study was conducted to investigate safety and immunogenicity in non-resectable pancreatic carcinoma patients using a 16-amino acid telomerase peptide (GV1001) for vaccination in combination with GM-CSF and gemcitabine as first line treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "endSection": "abstract" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1596, "text": "Telomerase vaccination (GV1001) in combination with chemotherapy appeared to be safe but the immune responses were weak and transient. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24954781", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "BACKGROUND: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24954781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Novel vaccine peptide GV1001 effectively blocks \u03b2-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1379, "text": "Together, these results suggest that GV1001 possesses neuroprotective effects against A\u03b2\u2082\u2085\u208b\u2083\u2085 oligomer in NSCs and that these effects are mediated through mimicking the extra-telomeric functions of human telomerase reverse transcriptase, including the induction of cellular proliferation, anti-apoptotic effects, mitochondrial stabilization, and anti-aging and anti-oxidant effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 307, "text": "Peptide GV1001 is a peptide vaccine representing a 16-amino acid human telomerase reverse transcriptase sequence, which has been reported to possess potential antineoplastic and anti-inflammatory activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24815142", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1232, "text": "Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23827187", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 784, "text": "Of the increasing number of immunological agents, the GV1001 antitelomerase vaccine holds some interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19072345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24411674", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 498, "text": "Peptide GV1001 is a peptide vaccine representing a 16-amino acid human telomerase reverse transcriptase sequence, which has been reported to possess potential antineoplastic and anti-inflammatory activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24815142", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 678, "text": "It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "GV1001 is a telomerase-specific, promiscuous class II peptide vaccine which is currently in an advanced stage of clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The study is a proof-of-principle trial evaluating toxicity, immune response, and clinical response in melanoma patients after combined therapy with temozolomide and the telomerase peptide vaccine GV1001.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21586625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21377838", "endSection": "title" }, { "offsetInBeginSection": 136, "offsetInEndSection": 488, "text": "This article reviews the biological rationale underpinning the design of ongoing studies with the vaccine as well as its immunogenicity and clinical activity. It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822343", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 491, "text": "It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822343", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 496, "text": "Human telomerase reverse transcriptase (hTERT), the rate-limiting subunit of the telomerase complex, is therefore an attractive target for cancer vaccination. The present review provides an update on the development of GV1001, a peptide vaccine representing a 16-aa hTERT sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19388882", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 488, "text": "It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822343", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 686, "text": "Of the increasing number of immunological agents, the GV1001 antitelomerase vaccine holds some interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19072345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1233, "text": "Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841437", "endSection": "abstract" } ] }, { "body": "Which is the E3 ubiquitin ligase which ubiquitinates IkB leading to its proteasomal degradation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22435548", "http://www.ncbi.nlm.nih.gov/pubmed/17001349", "http://www.ncbi.nlm.nih.gov/pubmed/16778892", "http://www.ncbi.nlm.nih.gov/pubmed/10837071", "http://www.ncbi.nlm.nih.gov/pubmed/20028970" ], "ideal_answer": [ "I\u03baB degradation involves ubiquitination mediated by a specific E3 ubiquitin ligase SCF(\u03b2-TrCP). SCF(\u03b2-TrCP) -mediated I\u03baB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor I\u03baB\u03b1 within a few minutes of cell stimulation.", "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase.Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation.", "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase. SCF(\u03b2-TrCP) -mediated I\u03baB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor I\u03baB\u03b1 within a few minutes of cell stimulation." ], "exact_answer": [ "SCF(\u03b2-TrCP)", "SCF beta-transducin repeat-containing protein (beta-TrCP)", "beta-Trcp" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044767" ], "type": "factoid", "id": "550af222c2af5d5b7000000b", "snippets": [ { "offsetInBeginSection": 600, "offsetInEndSection": 1200, "text": "IKK activation and I\u03baB degradation involve different ubiquitination modes; the latter is mediated by a specific E3 ubiquitin ligase SCF(\u03b2-TrCP) . The F-box component of this E3, \u03b2-TrCP, recognizes the I\u03baB degron formed following phosphorylation by IKK and thus couples I\u03baB phosphorylation to ubiquitination. SCF(\u03b2-TrCP) -mediated I\u03baB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor I\u03baB\u03b1 within a few minutes of cell stimulation. In vivo ablation of \u03b2-TrCP results in accumulation of all the I\u03baBs and complete NF-\u03baB inhibition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22435548", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 710, "text": "Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20028970", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 548, "text": "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17001349", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 1100, "text": "Here we show that beta-catenin stabilizes the mRNA encoding the F-box protein betaTrCP1, and identify the RNA-binding protein CRD-BP (coding region determinant-binding protein) as a previously unknown target of beta-catenin/Tcf transcription factor. CRD-BP binds to the coding region of betaTrCP1 mRNA. Overexpression of CRD-BP stabilizes betaTrCP1 mRNA and elevates betaTrCP1 levels (both in cells and in vivo), resulting in the activation of the Skp1-Cullin1-F-box protein (SCF)(betaTrCP) E3 ubiquitin ligase and in accelerated turnover of its substrates including IkappaB and beta-catenin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16778892", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 2122, "text": " The multisubunit IkappaB kinase (IKK) responsible for inducible IkappaB phosphorylation is the point of convergence for most NF-kappaB-activating stimuli. IKK contains two catalytic subunits, IKKalpha and IKKbeta, both of which are able to correctly phosphorylate IkappaB. Gene knockout studies have shed light on the very different physiological functions of IKKalpha and IKKbeta. After phosphorylation, the IKK phosphoacceptor sites on IkappaB serve as an essential part of a specific recognition site for E3RS(IkappaB/beta-TrCP), an SCF-type E3 ubiquitin ligase, thereby explaining how IKK controls IkappaB ubiquitination and degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10837071", "endSection": "abstract" } ] }, { "body": "Is c-met involved in the activation of the Akt pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17258200", "http://www.ncbi.nlm.nih.gov/pubmed/23345546", "http://www.ncbi.nlm.nih.gov/pubmed/14570904", "http://www.ncbi.nlm.nih.gov/pubmed/18234991", "http://www.ncbi.nlm.nih.gov/pubmed/22820099", "http://www.ncbi.nlm.nih.gov/pubmed/22789825", "http://www.ncbi.nlm.nih.gov/pubmed/17942284", "http://www.ncbi.nlm.nih.gov/pubmed/15522281", "http://www.ncbi.nlm.nih.gov/pubmed/10714768", "http://www.ncbi.nlm.nih.gov/pubmed/17464994", "http://www.ncbi.nlm.nih.gov/pubmed/21536148", "http://www.ncbi.nlm.nih.gov/pubmed/19850646", "http://www.ncbi.nlm.nih.gov/pubmed/11821397", "http://www.ncbi.nlm.nih.gov/pubmed/18262389", "http://www.ncbi.nlm.nih.gov/pubmed/20233866", "http://www.ncbi.nlm.nih.gov/pubmed/21687953", "http://www.ncbi.nlm.nih.gov/pubmed/16278380", "http://www.ncbi.nlm.nih.gov/pubmed/23229794" ], "ideal_answer": [ "HGF-induced activation of c-Met is playing a pivotal role in the stimulation of c-Src activation, resulting in induction of phosphatidylinositol 3-kinase complexes p85\u03b1/p110\u03b1 and p85\u03b1/p110\u03b4, which is required for Akt-mediated activation of mammalian target of rapamycin, with consequent inhibition of I\u03baB kinase and nuclear factor-\u03baB activation, resulting in enhanced cell survival." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048012", "http://www.uniprot.org/uniprot/SLTM_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051896", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051057", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019859", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043491", "http://www.uniprot.org/uniprot/AKT1_HUMAN" ], "type": "yesno", "id": "5318a955b166e2b806000020", "snippets": [ { "offsetInBeginSection": 421, "offsetInEndSection": 726, "text": "Amplification of MET has been reported in approximately 5%-22% of lung tumors with acquired resistance to small-molecule inhibitors of the epidermal growth factor receptor (EGFR). Resistance to EGFR inhibitors is likely mediated through downstream activation of the phosphoinositide 3-kinase /AKT pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23345546", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 965, "text": "Simultaneous treatment of resistant tumors with a MET inhibitor plus an EGFR inhibitor can abrogate activation of downstream effectors of cell growth, proliferation, and survival, thereby overcoming acquired resistance to EGFR inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23345546", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 885, "text": "HGF mediated both ERK and Akt phosphorylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229794", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1360, "text": "ERK/Akt signaling, but not the Smad pathway, may be one of the main processes in HGF-induced EMT,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229794", "endSection": "abstract" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1503, "text": "The MAPK/Akt pathway is indispensable in HGF/c-Met signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820099", "endSection": "title" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1083, "text": "Specifically, we demonstrated that inhibition of c-Met activity led to suppression of the PI3K-Akt pathway, thus enhancing cisplatin chemosensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820099", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1245, "text": "Our study clearly suggests that inhibition of c-Met activity can effectively sensitize osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820099", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 806, "text": "We found that a dual Met/VEGF receptor 2 kinase inhibitor, E7050, circumvented HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer cell lines by inhibiting the Met/Gab1/PI3K/Akt pathway in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22789825", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 728, "text": "Here, we report that i) treatment of RL95-2 cells with HGF resulted in phosphorylation of the HGF receptor c-Met, activation of Akt and I\u03baB, translocation of NF-\u03baB into the nucleus, and up-regulation of COX-2 mRNA;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21687953", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1205, "text": "Our data suggest that HGF possesses chemotactic ability, has anti-apoptosis action, and induces cellular infiltration via the PI3K/Akt pathway;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21687953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Hepatocyte growth factor-induced c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway inhibits dendritic cell activation by blocking I\u03baB kinase activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21536148", "endSection": "title" }, { "offsetInBeginSection": 715, "offsetInEndSection": 938, "text": "Activation of c-Src in turn establishes a complex consisting of phosphatidylinositol 3-kinase and c-MET, and promotes downstream activation of the phosphatidylinositol 3-kinase/AKT pathway and mammalian target of rapamycin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21536148", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1443, "text": "Notably, hepatocyte growth factor-stimulated c-Src activation results in induction of phosphatidylinositol 3-kinase complexes p85\u03b1/p110\u03b1 and p85\u03b1/p110\u03b4, which is required for activation of mammalian target of rapamycin, and consequent inhibition of I\u03baB kinase and nuclear factor-\u03baB activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21536148", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1735, "text": "Our findings, for the first time, have identified the c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway that plays a pivotal role in mediating the inhibitory effects of hepatocyte growth factor on dendritic cell activation by blocking nuclear factor-\u03baB signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21536148", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1487, "text": "Cyr61 siRNA inhibited a second phase of Akt phosphorylation measured 12 hours after cell stimulation with HGF and also inhibited HGF-induced phosphorylation of the Akt target glycogen synthase kinase 3alpha.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20233866", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1594, "text": "HGF+EGF treatment increased the duration of ERK1/2 and AKT activation compared to HGF or EGF alone. All these data indicate that a crosstalk between the EGF and HGF pathways in mammary epithelial cells may modulate the development of the mammary gland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19850646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Hepatocyte growth factor and c-Met promote dendritic maturation during hippocampal neuron differentiation via the Akt pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18262389", "endSection": "title" }, { "offsetInBeginSection": 758, "offsetInEndSection": 1053, "text": "Consistent with these results, HGF activated Akt, which phosphorylates glycogen synthase kinase-3beta (GSK-3beta) to inactivate it, and reduced phosphorylation of microtubule-associated protein 2 (MAP2), which can promote microtubule polymerization and dendrite elongation when dephosphorylated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18262389", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1374, "text": "Conversely, pharmacological inhibition of c-Met with its specific inhibitor, PHA-665752, or genetic knock-down of c-Met with short hairpin RNAs (shRNAs) suppressed HGF-induced phosphorylation of Akt and GSK-3beta, increased phosphorylation of MAP2, and reduced dendrite number and length in cultured hippocampal neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18262389", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1699, "text": "Inhibiting Akt activity with the phosphoinositide-3-kinase inhibitor LY294002 or Akt inhibitor X suppressed HGF-induced phosphorylation of GSK-3beta, increased MAP2 phosphorylation, and blocked the ability of HGF to enhance dendritic length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18262389", "endSection": "abstract" }, { "offsetInBeginSection": 1700, "offsetInEndSection": 1844, "text": "These observations indicate that HGF and c-Met can regulate the early stages of dendrite maturation via activation of the Akt/GSK-3beta pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18262389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18234991", "endSection": "title" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1415, "text": "HGF was found to enhance cell migration, and that HGF-induced migration depends on PI3K/Akt pathway. The activation of PI3K/Akt pathway induced by the HGF/c-Met axis is involved in the downregulation of cell adhesion molecules E-cadherin and beta-catenin, contributing to the attenuation of cell-cell adhesion and promoting the enhanced motility and migration of uveal melanoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18234991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "HGF protects cultured cortical neurons against hypoxia/reoxygenation induced cell injury via ERK1/2 and PI-3K/Akt pathways", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942284", "endSection": "title" }, { "offsetInBeginSection": 462, "offsetInEndSection": 528, "text": "HGF stimulated both ERK1/2 and Akt activities in cortical neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942284", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 718, "text": "Inhibition of ERK activation completely abolished the protective effects of HGF, and inhibition of Akt activation reduced, but did not completely eliminate the HGF mediated neuroprotection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942284", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 837, "text": "It is suggested that the neuroprotection of HGF depend on ERK1/2 pathway, and, to a lesser extent, PI-3K/Akt pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17464994", "endSection": "title" }, { "offsetInBeginSection": 1318, "offsetInEndSection": 1488, "text": "Thus, Met acting on PI3K and Akt ensures high levels of FLIPL, and disruption of this pathway contributes to hepatic apoptosis and possibly to Fas-related liver diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17464994", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 990, "text": "The HGF-induced increase in Nkx 2.5 expression was inhibited by co-treatment with the PI3 kinase inhibitors Wortmannin and LY294002, but not by its inactive homolog LY303511, suggesting an involvement of the PI3 kinase/Akt pathway in this effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17258200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16278380", "endSection": "title" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1347, "text": "Activation of XIAP expression by HGF was inhibited by siRNA targeting Akt1 and Akt2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16278380", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1419, "text": "Activation of C-MET enhances XIAP through the Akt pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16278380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15522281", "endSection": "title" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1331, "text": "A significant reduction in apoptosis in the HGF-treated hearts was observed compared with control hearts, and was strongly associated with increased Akt activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15522281", "endSection": "abstract" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1546, "text": "The antiapoptotic effect of HGF was mediated by activation of PI3-kinase/Akt pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15522281", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 874, "text": "The protective effect of HGF/SF against the ADR-induced apoptosis was abolished in the presence of either LY294002, an inhibitor of phosphatidylinositol-3'-OH kinase (PI3-K) or 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, an inhibitor of Akt, thus implicating the activation of PI3-K-Akt signaling in the antiapoptotic action of HGF/SF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570904", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 985, "text": "Immunoblotting analysis revealed that HGF/SF stimulated the sustained phosphorylation of Akt for several hours", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570904", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1185, "text": "Furthermore, ADR-induced activation of caspase-9, a downstream molecule of Akt, was inhibited for at least 24 h after HGF/SF stimulation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570904", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1656, "text": "These results indicate that HGF/SF, but not EGF, transmitted protective signals against ADR-induced apoptosis by causing sustained activation of the PI3-K-Akt signaling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Hepatocyte growth factor/scatter factor inhibits UVB-induced apoptosis of human keratinocytes but not of keratinocyte-derived cell lines via the phosphatidylinositol 3-kinase/AKT pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11821397", "endSection": "title" }, { "offsetInBeginSection": 349, "offsetInEndSection": 575, "text": "When we analyzed the signaling pathways initiated by the HGF/SF receptor c-met, we found that the phosphatidylinositol (PI) 3-kinase and its downstream-element AKT and the mitogen-activated protein (MAP) kinase were activated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11821397", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 728, "text": "Inhibition of PI 3-kinase led to a complete abrogation of the anti-apoptotic effect of HGF/SF, whereas blockade of the MAP kinase pathway had no effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11821397", "endSection": "abstract" }, { "offsetInBeginSection": 1261, "offsetInEndSection": 1411, "text": "We now show in detached cells a cooperative effect of HGF and FN in the activation of PI 3-kinase and on the phosphorylation of PKB/Akt at serine 473.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10714768", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1554, "text": "PI 3-kinase activity is also required for the HGF- and fibronectin-induced survival responses, as well as anchorage-independent colony growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10714768", "endSection": "abstract" }, { "offsetInBeginSection": 1645, "offsetInEndSection": 1964, "text": "Together, these results demonstrate that the PI 3-kinase/Akt pathway is a key effector of the HGF- and fibronectin-induced survival response of breast carcinoma cells under detached conditions and corroborate an interaction between integrin and HGF/ Met signalling pathways in the development of invasive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10714768", "endSection": "abstract" } ] }, { "body": "Is pregnancy an additional risk during during H1N1 infection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22901103", "http://www.ncbi.nlm.nih.gov/pubmed/22551713", "http://www.ncbi.nlm.nih.gov/pubmed/22782418", "http://www.ncbi.nlm.nih.gov/pubmed/22482974", "http://www.ncbi.nlm.nih.gov/pubmed/22851818", "http://www.ncbi.nlm.nih.gov/pubmed/20148081", "http://www.ncbi.nlm.nih.gov/pubmed/24051575", "http://www.ncbi.nlm.nih.gov/pubmed/22515877", "http://www.ncbi.nlm.nih.gov/pubmed/22859826", "http://www.ncbi.nlm.nih.gov/pubmed/22331165", "http://www.ncbi.nlm.nih.gov/pubmed/22564554", "http://www.ncbi.nlm.nih.gov/pubmed/21596080", "http://www.ncbi.nlm.nih.gov/pubmed/21756329", "http://www.ncbi.nlm.nih.gov/pubmed/20531946", "http://www.ncbi.nlm.nih.gov/pubmed/20100064", "http://www.ncbi.nlm.nih.gov/pubmed/21913391", "http://www.ncbi.nlm.nih.gov/pubmed/22411229", "http://www.ncbi.nlm.nih.gov/pubmed/19643469", "http://www.ncbi.nlm.nih.gov/pubmed/21252793", "http://www.ncbi.nlm.nih.gov/pubmed/22030045", "http://www.ncbi.nlm.nih.gov/pubmed/23116790", "http://www.ncbi.nlm.nih.gov/pubmed/22272853", "http://www.ncbi.nlm.nih.gov/pubmed/22120858" ], "ideal_answer": [ "Pregnant women are at increased risk for complications from pandemic influenza H1N1 virus infection. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. Pregnancy, particularly during the third trimester, increases the risk of complications and early antiviral treatment is associated with improved outcomes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018566", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053118", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247" ], "type": "yesno", "id": "531a3fe3b166e2b806000038", "snippets": [ { "offsetInBeginSection": 495, "offsetInEndSection": 566, "text": "H1N1 influenza in pregnancy can be associated with severe complications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20148081", "endSection": "abstract" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1560, "text": "This case series confirms a high number of complications in pregnant women due to pandemic H1N1/09.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100064", "endSection": "abstract" }, { "offsetInBeginSection": 1841, "offsetInEndSection": 1936, "text": "Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19643469", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1592, "text": "Pregnant women are at increased risk for complications from pandemic influenza H1N1 virus infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22030045", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1756, "text": "Vaccination of pregnant women against influenza A (H1N1) by Russian subunit formulation (MonoGrippol plus) showed reactogenicity comparable to control group by the level of influence on general metabolic and immunologic homeostasis and on the course of pregnancy, which is an evidence of its safety", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913391", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 284, "text": "Pregnancy was identified as a major risk factor for increased mortality and morbidity due to H1N1 influenza in the pandemic of 2009 to 2010", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21756329", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1285, "text": "While it is not possible to ascertain retrospectively if myocarditis was caused by either infection with H1N1 virus or as a result of pregnancy (in the absence of endomyocardial biopsies), the significant association with myocardial involvement in both women demonstrates the increased risk of exposure to H1N1 influenza virus in pregnant women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21756329", "endSection": "abstract" }, { "offsetInBeginSection": 1664, "offsetInEndSection": 1940, "text": "Although limited in size, the fully prospective nature of the safety follow-up of these women vaccinated during pregnancy is unique and offers an important degree of reassurance for the use of the AS03 adjuvanted H1N1 (2009) vaccine in this high risk group for H1N1 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596080", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 320, "text": "During the H1N1 2009 pandemic, pregnant women constituted one of the priority groups for vaccination in many countries, creating a need for close monitoring of the safety of the vaccine in pregnant women", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596080", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 154, "text": "Emerging data suggest that pregnancy conveys high risk for severe complications from the 2009 pandemic influenza A virus (2009 H1N1) infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21252793", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 199, "text": "Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20531946", "endSection": "abstract" }, { "offsetInBeginSection": 1567, "offsetInEndSection": 1681, "text": "This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20531946", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1230, "text": "The results of our study do not indicate a risk for the pregnant woman and the developing embryo/fetus after H1N1 vaccination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22564554", "endSection": "abstract" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1704, "text": "This large cohort study found no evidence of an increased risk of fetal death associated with exposure to an adjuvanted pandemic A/H1N1 2009 influenza vaccine during pregnancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22551713", "endSection": "abstract" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1158, "text": "Our results suggest that second- or third-trimester H1N1 vaccination was associated with improved fetal and neonatal outcomes during the recent pandemic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22515877", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 278, "text": "Pregnant women might thus be at increased risk of complications from pandemic H1N1 virus infection, and illness may progress rapidly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22482974", "endSection": "abstract" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1332, "text": "Pregnant women with H1N1 infection seem to benefit from antiviral therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22482974", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 863, "text": "arly identification and treatment were the most important factors in different countries and areas examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22411229", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1013, "text": "The vaccine and antiviral drugs that have been the most efficient means to control the novel virus appear to be safe but require more extensive study", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22411229", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 987, "text": "However, there were significant differences between the two groups in relation to mean age, treatment with oseltamivir, schooling, and presence of other risk factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22331165", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 286, "text": "To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22782418", "endSection": "abstract" }, { "offsetInBeginSection": 2168, "offsetInEndSection": 2386, "text": "In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22782418", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 755, "text": "Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22851818", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1216, "text": "Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22851818", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1678, "text": "The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22851818", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 249, "text": "regnant women were at increased risk for serious outcomes of 2009 pandemic influenza A virus subtype H1N1 (influenza A[H1N1]pdm09) infection, but little is known about the overall impact of the pandemic on neonatal and maternal outcomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859826", "endSection": "abstract" }, { "offsetInBeginSection": 1572, "offsetInEndSection": 1700, "text": "In this large, geographically diverse population, A(H1N1)pdm09 infection increased the risk for hospitalization during pregnancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859826", "endSection": "abstract" }, { "offsetInBeginSection": 1358, "offsetInEndSection": 1582, "text": "Vaccination during pregnancy with Pandemrix(\u00ae) appeared to have no ill effects on the pregnancy. On the contrary, the rate of preterm birth and low birthweight was lower than expected, which agrees with some previous results", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22901103", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 745, "text": "During the influenza A(H1N1)pmd09 pandemic, although many cases occurred in younger adults, the risk factors identified for severe infections and complications were similar to those for seasonal influenza, including chronic respiratory, renal, liver, and heart diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116790", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1228, "text": "In terms of pregnancy, the studies have shown contradictory results due to variations in methodology and medical care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116790", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1413, "text": "However, it seems that pregnancy, particularly during the third trimester, increases the risk of complications, and that early antiviral treatment is associated with improved outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116790", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1024, "text": "Pregnant women with mild clinical illness secondary to 2009 H1N1 were not at a greater risk of adverse pregnancy outcomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24051575", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1098, "text": "However, severely infected women were more likely to deliver SGA infants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24051575", "endSection": "abstract" }, { "offsetInBeginSection": 1852, "offsetInEndSection": 1984, "text": "Gestational age is associated with the risk of developing critical infection. The risk increases with increasing weeks of gestation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120858", "endSection": "abstract" }, { "offsetInBeginSection": 67, "offsetInEndSection": 205, "text": " Following the start of winter in Liaoning province in China, the number of pregnant women infected with influenza increased significantly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120858", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 236, "text": "regnancy, with or without additional complications, constitutes a high-risk condition for complications of influenza infection and warrants early intervention with neuraminidase inhibitors such as oseltamivir, if influenza is suspected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272853", "endSection": "abstract" } ] }, { "body": "Are long non coding RNAs as conserved in sequence as protein coding genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21112873", "http://www.ncbi.nlm.nih.gov/pubmed/23467124", "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "http://www.ncbi.nlm.nih.gov/pubmed/22844254", "http://www.ncbi.nlm.nih.gov/pubmed/22708672", "http://www.ncbi.nlm.nih.gov/pubmed/23463798", "http://www.ncbi.nlm.nih.gov/pubmed/23028352", "http://www.ncbi.nlm.nih.gov/pubmed/20428234", "http://www.ncbi.nlm.nih.gov/pubmed/20624288", "http://www.ncbi.nlm.nih.gov/pubmed/22707570", "http://www.ncbi.nlm.nih.gov/pubmed/21622663", "http://www.ncbi.nlm.nih.gov/pubmed/20587619", "http://www.ncbi.nlm.nih.gov/pubmed/23454638" ], "ideal_answer": [ "No. Most long non coding RNAs (lncRNAs) are under lower sequence constraints than protein-coding genes." ], "exact_answer": "no", "type": "yesno", "id": "51757bbb8ed59a060a00002e", "snippets": [ { "offsetInBeginSection": 101, "offsetInEndSection": 265, "text": "Most lncRNAs are under lower sequence constraints than protein-coding genes and lack conserved secondary structures, making it hard to predict them computationally.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21622663", "endSection": "sections.0" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1166, "text": "hey are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "sections.0" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1243, "text": "bout one-third seem to have arisen within the primate lineage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "sections.0" } ] }, { "body": "Mutation of which gene is implicated in the Brain-lung-thyroid syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22166853", "http://www.ncbi.nlm.nih.gov/pubmed/20020530", "http://www.ncbi.nlm.nih.gov/pubmed/25759798", "http://www.ncbi.nlm.nih.gov/pubmed/26196025", "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "http://www.ncbi.nlm.nih.gov/pubmed/24171694", "http://www.ncbi.nlm.nih.gov/pubmed/23430038", "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "http://www.ncbi.nlm.nih.gov/pubmed/21867529" ], "ideal_answer": [ "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations." ], "exact_answer": [ "thyroid transcription factor 1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "factoid", "id": "56c1f03bef6e394741000053", "snippets": [ { "offsetInBeginSection": 151, "offsetInEndSection": 362, "text": " The disorder is caused by mutations to the NKX2.1 (TITF1) gene and also forms part of the \"brain-lung-thyroid syndrome\", in which additional developmental abnormalities of lung and thyroid tissue are observed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26196025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Novel NKX2-1 Frameshift Mutations in Patients with Atypical Phenotypes of the Brain-Lung-Thyroid Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759798", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "OBJECTIVES: To verify the involvement of NKX2-1 gene in infants with brain-lung-thyroid (BLT) syndrome and hypothyroid phenotypes variable among congenital hypothyroidism (CH) or idiopathic mild hypothyroidism (IMH) of postnatal onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759798", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 988, "text": "They were carriers of new de novo heterozygous frameshift mutations of NKX2-1 (c.177delG and c.153_166del14).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759798", "endSection": "abstract" }, { "offsetInBeginSection": 1273, "offsetInEndSection": 1444, "text": "CONCLUSIONS: Two novel heterozygous frameshift mutations of NKX2-1 were identified in 2 cases selected on the basis of a BLT-like phenotype among 183 hypothyroid infants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 1250, "text": "Two of the four patients presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1 [c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this raises the possibility of mitochondrial mutations contributing to thyroid dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological, and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities will enable a unifying diagnosis and genetic counseling for the affected families. In addition, identification of an NKX2-1 defect would be helpful in allaying the concerns about inadequate thyroxine supplementation as the cause of neurological defects observed in some children with congenital hypothyroidism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 377, "text": "Loss-of-function mutations in NKX2.1, a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a number of individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND: NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1057, "text": "CONCLUSION: MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Mutations in NKX2-1 cause neurological, pulmonary, and thyroid hormone impairment. Recently, the disease was named brain-lung-thyroid syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22166853", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 808, "text": "Genetic analysis of NKX2-1 revealed a novel missense mutation (p.Val205Phe) in two patients who were cousins and their maternal families, and a novel 2.6-Mb deletion including NKX2-1 on chromosome 14 in the other patient. Congenital hypothyroidism was not detected on neonatal screening in the patient with the missense mutation, and frequent respiratory infections were observed in the patient with the deletion in NKX2-1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22166853", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 420, "text": "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867529", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 607, "text": "We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867529", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1522, "text": "In conclusion, ILD in patients with NKX2-1 mutations was associated with altered surfactant protein metabolism, and both gain and loss of function of the mutated NKX2-1 genes on surfactant protein promoters were associated with ILD in \"Brain-Lung-Thyroid syndrome\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20020530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 751, "text": "The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain-lung-thyroid syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in \"Brain-Lung-Thyroid Syndrome\".", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20020530", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Multiplex Ligation-dependent Probe Amplification improves the detection rate of NKX2.1 mutations in patients affected by brain-lung-thyroid syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "endSection": "abstract" }, { "offsetInBeginSection": 1173, "offsetInEndSection": 1376, "text": "The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 673, "text": "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1179, "text": "The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1262, "text": "In conclusion, ILD in patients with NKX2-1 mutations was associated with altered surfactant protein metabolism, and both gain and loss of function of the mutated NKX2-1 genes on surfactant protein promoters were associated with ILD in \"Brain-Lung-Thyroid syndrome\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20020530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND: NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1060, "text": "CONCLUSION: MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 487, "text": "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain-lung-thyroid syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": " Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867529", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 362, "text": "The disorder is caused by mutations to the NKX2.1 (TITF1) gene and also forms part of the \"brain-lung-thyroid syndrome\", in which additional developmental abnormalities of lung and thyroid tissue are observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26196025", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 494, "text": "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 408, "text": "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in \"Brain-Lung-Thyroid Syndrome\".", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20020530", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Novel NKX2-1 Frameshift Mutations in Patients with Atypical Phenotypes of the Brain-Lung-Thyroid Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759798", "endSection": "title" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1179, "text": "The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Mutations in the gene encoding thyroid transcription factor, NKX2-1, result in neurologic abnormalities, hypothyroidism, and neonatal respiratory distress syndrome (RDS) that together are known as the brain-thyroid-lung syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23430038", "endSection": "abstract" } ] }, { "body": "What is clathrin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24322426", "http://www.ncbi.nlm.nih.gov/pubmed/23093191", "http://www.ncbi.nlm.nih.gov/pubmed/19809570", "http://www.ncbi.nlm.nih.gov/pubmed/12952941", "http://www.ncbi.nlm.nih.gov/pubmed/22042622", "http://www.ncbi.nlm.nih.gov/pubmed/24307937", "http://www.ncbi.nlm.nih.gov/pubmed/24280271", "http://www.ncbi.nlm.nih.gov/pubmed/24263003", "http://www.ncbi.nlm.nih.gov/pubmed/24299503", "http://www.ncbi.nlm.nih.gov/pubmed/21445329", "http://www.ncbi.nlm.nih.gov/pubmed/24257253" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11597306", "o": "GO:0030276" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1149166", "o": "http://linkedlifedata.com/resource/umls/label/A11597306" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1149166", "o": "http://linkedlifedata.com/resource/umls/label/A11597306" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11597306", "o": "clathrin binding" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0030136", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0030135" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0030135", "o": "coated vesicle" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0030136", "o": "clathrin-coated vesicle" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A14252573", "o": "GO:0030119" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1749488", "o": "http://linkedlifedata.com/resource/umls/label/A14252573" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14252573", "o": "clathrin adaptor" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1749488", "o": "http://linkedlifedata.com/resource/umls/label/A14252573" }, { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0030276", "o": "molecular_function" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0030276", "o": "clathrin binding" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11615777", "o": "GO:0030100" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11615777", "o": "regulation of endocytosis" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1159767", "o": "http://linkedlifedata.com/resource/umls/label/A11615777" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1159767", "o": "http://linkedlifedata.com/resource/umls/label/A11615777" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A14275283", "o": "GO:0045807" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14275283", "o": "activation of endocytosis" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2249588", "o": "http://linkedlifedata.com/resource/umls/label/A14275283" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2249588", "o": "http://linkedlifedata.com/resource/umls/label/A14275283" } ], "ideal_answer": [ "Clathrin helps build small vesicles in order to safely transport molecules within and between cells." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030118", "http://www.uniprot.org/uniprot/CLCA_MOUSE", "http://www.uniprot.org/uniprot/CLCA_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D033922", "http://www.uniprot.org/uniprot/CLCA_BOVIN", "http://www.uniprot.org/uniprot/CLC1_SCHPO", "http://www.uniprot.org/uniprot/CLC_DICDI", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030119", "http://www.uniprot.org/uniprot/CLC1_YEAST", "http://www.biosemantics.org/jochem#4250446", "http://www.uniprot.org/uniprot/EPN4_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D033942", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D033941", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030276", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071439", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002966", "http://www.uniprot.org/uniprot/EPN4_MOUSE", "http://www.uniprot.org/uniprot/CLCA_HUMAN", "http://www.uniprot.org/uniprot/CLC_DROME" ], "type": "summary", "id": "52d946c798d023950500000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Clathrin-mediated endocytosis is a central and well-studied trafficking process in eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24322426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "We reported the first small molecule inhibitors of the interaction between the clathrin N-terminal domain (TD) and endocyctic accessory proteins (i.e., clathrin inhibition1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24299503", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 185, "text": "Tubulobulbar complexes are elaborate clathrin/actin related structures that form at sites of intercellular attachment in the seminiferous epithelium of the mammalian testis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24280271", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 222, "text": " Clathrin-coated vesicles (CCVs) are formed at the plasma membrane and act as vectors for endocytosis. They also assemble at the trans-Golgi network (TGN), but their exact function at this organelle is unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24263003", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1329, "text": " Clathrin immunohistochemistry and immunoblotting showed increased immunoreactivity of clathrin protein in the placental tissues of mice treated with 20- and 50-nm gold nanoparticles; clathrin immunopositivity was observed in syncytiotrophoblasts and fetal endothelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257253", "endSection": "abstract" } ] }, { "body": "What are the main results of PRKAR1A Knockdown?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20824711", "http://www.ncbi.nlm.nih.gov/pubmed/24122441", "http://www.ncbi.nlm.nih.gov/pubmed/16937372", "http://www.ncbi.nlm.nih.gov/pubmed/23480756" ], "ideal_answer": [ "Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis. Also, Knockdown of the cAMP-dependent protein kinase (PKA) Type Ialpha regulatory subunit in mouse oocytes disrupts meiotic arrest and results in meiotic spindle defects." ], "concepts": [ "http://www.uniprot.org/uniprot/KAP0_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055785" ], "type": "summary", "id": "5322d9339b2d7acc7e000011", "snippets": [ { "offsetInBeginSection": 1583, "offsetInEndSection": 1766, "text": "These results show that RI\u03b1 inactivation leads to multiple, compartment-specific alterations of the cAMP/PKA pathway revealing new aspects of signaling dysregulation in tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24122441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23480756", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 926, "text": "Silencing PRKAR1A expression induced growth inhibition and apoptosis of CCA cells, with an associated decrease in mitogen-activated protein kinases, PI3K/Akt, JAK/STAT and Wnt/\u03b2-catenin pathway signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20824711", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1037, "text": "The inhibition of PKA using a PKA inhibitor and cAMP analogs also led to a significant cell growth inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20824711", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1317, "text": "abrogation of gene expression caused significant CCA cell growth inhibition, oncogenic signaling and coupled apoptosis induction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20824711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Knockdown of the cAMP-dependent protein kinase (PKA) Type Ialpha regulatory subunit in mouse oocytes disrupts meiotic arrest and results in meiotic spindle defects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16937372", "endSection": "title" }, { "offsetInBeginSection": 820, "offsetInEndSection": 976, "text": "These results demonstrate that RIalpha is required for regulating PKA activity in maturing oocytes and that compensatory upregulation of RII does not occur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16937372", "endSection": "abstract" } ] }, { "body": "Is TENS machine effective in pain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7644247", "http://www.ncbi.nlm.nih.gov/pubmed/17333874" ], "ideal_answer": [ "Transcutaneous electrical nerve stimulation is widely used in pain management" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018710", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010146", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059350", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004561" ], "type": "yesno", "id": "535d75ab7d100faa09000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Transcutaneous electrical nerve stimulation is widely used in pain management but its effectiveness depends on the stimulation being targeted appropriately", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17333874", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 146, "text": "hypoalgesic effects of transcutaneous electrical nerve stimulation upon experimentally induced ischaemic pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7644247", "endSection": "title" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1416, "text": "The results of this study have provided evidence of the hypoalgesic effects of TENS upon experimental ischaemic pain which were found to be frequency specific with the lower frequency used here (4 Hz) demonstrating the only significant effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7644247", "endSection": "abstract" } ] }, { "body": "Is there any algorithm for enhancer identification from chromatin state?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23526891", "http://www.ncbi.nlm.nih.gov/pubmed/22328731" ], "ideal_answer": [ "yes", "Yes. RFECS is a random-forest based algorithm for enhancer identification from chromatin state. It integrates histone modification profiles for the identification of enhancers, and can be used to identify enhancers in a number of cell-types. RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000465" ], "type": "yesno", "id": "56d1d14567f0cb3d66000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "RFECS: a random-forest based algorithm for enhancer identification from chromatin state.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526891", "endSection": "title" }, { "offsetInBeginSection": 348, "offsetInEndSection": 1249, "text": "However, only a limited number of cell types or chromatin marks have previously been investigated for this purpose, leaving the question unanswered whether there exists an optimal set of histone modifications for enhancer prediction in different cell types. Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. We show that RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526891", "endSection": "abstract" }, { "offsetInBeginSection": 1025, "offsetInEndSection": 1281, "text": "We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526891", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 1030, "text": "Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526891", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 722, "text": "ChromaGenSVM selects optimum combinations of specific histone epigenetic marks to predict enhancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328731", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1030, "text": "We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526891", "endSection": "abstract" } ] }, { "body": "Which enzyme is targeted by the drug Imetelstat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21208905", "http://www.ncbi.nlm.nih.gov/pubmed/23386830", "http://www.ncbi.nlm.nih.gov/pubmed/21549308", "http://www.ncbi.nlm.nih.gov/pubmed/23521791", "http://www.ncbi.nlm.nih.gov/pubmed/23558965", "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "http://www.ncbi.nlm.nih.gov/pubmed/20072842", "http://www.ncbi.nlm.nih.gov/pubmed/21845093", "http://www.ncbi.nlm.nih.gov/pubmed/23467584", "http://www.ncbi.nlm.nih.gov/pubmed/20232321", "http://www.ncbi.nlm.nih.gov/pubmed/21332640", "http://www.ncbi.nlm.nih.gov/pubmed/22382179", "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "http://www.ncbi.nlm.nih.gov/pubmed/23272238", "http://www.ncbi.nlm.nih.gov/pubmed/24327604", "http://www.ncbi.nlm.nih.gov/pubmed/23516479", "http://www.ncbi.nlm.nih.gov/pubmed/19908230", "http://www.ncbi.nlm.nih.gov/pubmed/23326372", "http://www.ncbi.nlm.nih.gov/pubmed/22870217", "http://www.ncbi.nlm.nih.gov/pubmed/20824134", "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "http://www.ncbi.nlm.nih.gov/pubmed/20048334", "http://www.ncbi.nlm.nih.gov/pubmed/23727752" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/umls/id/C2746063", "o": "NCI: A synthetic lipid-conjugated, 13-mer oligonucleotide N3'-P5'-thio-phosphoramidate with potential antineoplastic activity. Complementary to the template region of telomerase (hTR) RNA, telomerase inhibitor GRN163L as a competitive enzyme inhibitor that binds and blocks the active site of the enzyme (a telomerase template antagonist), a mechanism of action which differs from that for the antisense oligonucleotide-mediated inhibition of telomerase activity through telomerase mRNA binding. Inhibition of telomerase activity in tumor cells by telomerase inhibitor GRN163L results in telomere shortening, which leads to cell cycle arrest or apoptosis." }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17693237", "o": "IMETELSTAT" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17693235", "o": "Imetelstat" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2746063", "o": "http://linkedlifedata.com/resource/umls/label/A17693237" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2746063", "o": "http://linkedlifedata.com/resource/umls/label/A17693236" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2746063", "o": "http://linkedlifedata.com/resource/umls/label/A17693235" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17693236", "o": "DNA, d(3'-amino-3'-deoxy-P-thio)(T-A-G-G-G-T-T-A-G-A-C-A-A), 5'-[O-[2-hydroxy-3- [(1-oxohexadecyl)amino]propyl] hydrogen phosphorothioate]" } ], "ideal_answer": [ "Imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'\u2192P5' thio-phosphoramidate lipid conjugate, which represents the latest generation of telomerase inhibitors targeting the template region of the human functional telomerase RNA subunit. In preclinical trials, this compound has been found to inhibit telomerase activity in multiple cancer cell lines, as well as in vivo xenograft mouse models." ], "exact_answer": [ "Human Telomerase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004358" ], "type": "factoid", "id": "532498959b2d7acc7e000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Imetelstat (a telomerase antagonist) exerts off\u2011target effects on the cytoskeleton.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "endSection": "title" }, { "offsetInBeginSection": 228, "offsetInEndSection": 636, "text": "imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'\u2192P5' thio-phosphoramidate lipid conjugate, which represents the latest generation of telomerase inhibitors targeting the template region of the human functional telomerase RNA (hTR) subunit. In preclinical trials, this compound has been found to inhibit telomerase activity in multiple cancer cell lines, as well as in vivo xenograft mouse models. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1017, "text": "In addition to the inhibition of telomerase activity in cancer cell lines, GRN163L causes morphological cell rounding changes, independent of hTR expression or telomere length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 421, "text": "We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 695, "text": "Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 691, "text": " Telomerase extension is less processive during the first few weeks following the reversal of long-term treatment with the telomerase inhibitor Imetelstat (GRN163L), a time when Cajal bodies fail to deliver telomerase RNA to telomeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549308", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 883, "text": "The role of telomerase as an immunotherapy, as a gene therapy approach using telomerase promoter driven oncolytic viruses and as a small oligonucleotide targeted therapy (Imetelstat) will be discussed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21332640", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 811, "text": "We then tested the efficacy of the telomerase inhibitor Imetelstat on propagation and self-renewal capacity of TIC and normal stem cells in vitro and in vivo. R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208905", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 105, "text": "e telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "title" }, { "offsetInBeginSection": 455, "offsetInEndSection": 769, "text": "In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 700, "text": "Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20824134", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1205, "text": "Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20824134", "endSection": "abstract" }, { "offsetInBeginSection": 1666, "offsetInEndSection": 1851, "text": "Short oligonucleotide N3'-->P5' thio-phosphoramidate conjugated to 5'-palmitoyl group, designated as GRN163L (Imetelstat), was recently introduced as a potent human telomerase inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20232321", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 54, "text": "etelstat (GRN163L)--telomerase-based cancer therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20072842", "endSection": "title" }, { "offsetInBeginSection": 579, "offsetInEndSection": 703, "text": "Imetelstat (GRN163L) is a potent and specific telomerase inhibitor and so far the only drug of its class in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20072842", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 147, "text": "e telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048334", "endSection": "title" }, { "offsetInBeginSection": 108, "offsetInEndSection": 271, "text": "The effects of a novel human telomerase antagonist, imetelstat, on primary human glioblastoma (GBM) tumor-initiating cells were investigated in vitro and in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048334", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 961, "text": "Imetelstat treatment produced a dose-dependent inhibition of telomerase (IC(50) 0.45 micromol/L). Long-term imetelstat treatment led to progressive telomere shortening, reduced rates of proliferation, and eventually cell death in GBM tumor-initiating cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048334", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 1040, "text": " We have found that prostate TICs have significant telomerase activity which is inhibited by imetelstat sodium (GRN163L), a new telomerase antagonist that is currently in Phase I/II clinical trials for several hematological and solid tumor malignancies. Prostate TICs telomeres were of similar average length to the telomeres of the main population of cells and significant telomere shortening was detected in prostate TICs as a result of imetelstat treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19908230", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 677, "text": "Telomerase activation was countered by co-treatment with Imetelstat (GRN163L), a potent telomerase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516479", "endSection": "abstract" } ] }, { "body": "Which interleukins are inhibited by Dupilumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "http://www.ncbi.nlm.nih.gov/pubmed/25584909", "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "http://www.ncbi.nlm.nih.gov/pubmed/25645542", "http://www.ncbi.nlm.nih.gov/pubmed/24275927", "http://www.ncbi.nlm.nih.gov/pubmed/23688323" ], "ideal_answer": [ "Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels." ], "exact_answer": [ [ "interleukin-4" ], [ "interleukin-13" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007378" ], "type": "list", "id": "56c1f005ef6e39474100003a", "snippets": [ { "offsetInBeginSection": 450, "offsetInEndSection": 822, "text": "The world's first prospective controlled studies with the biologic human anti-IL4R antibody dupilumab for the indication \"atopic dermatitis\" were published in 2014. These motivated (1) to extend the studies to dupilumab and (2) to clinically test antagonization of other target molecules of TH2 polarized, atopic inflammation, e.g., IL-13, IL-31, IL-22, TSLP, and CRTH2. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25645542", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 850, "text": "Among the recently developed antiasthma biologic drugs, the monoclonal antibody dupilumab is very promising because of its ability to inhibit the biological effects of both IL-4 and IL-13. Indeed, dupilumab prevents IL-4/13 interactions with the \u03b1-subunit of the IL-4 receptor complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 310, "text": " In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor \u03b1, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1372, "text": "Examples include the efficacy of omalizumab in patients with severe refractory atopic asthma characterized by raised serum total IgE, mepolizumab, reslizumab, and benralizumab in patients with recurrent eosinophilic exacerbations characterized by blood and sputum eosinophilia despite high doses of corticosteroids, and lebrikizumab, pitrakinra, dupilumab, and tralokinumab that target the IL-4/IL-13 signalling pathways in patients with eosinophilic asthma or raised serum periostin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24275927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "BACKGROUND: Moderate-to-severe asthma remains poorly treated. We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1335, "text": "With respect to immune dysregulation, dupilumab, a fully human monoclonal antibody directed at the IL-4 receptor alpha subunit was recently shown to be effective in treating adults with moderate-to-severe AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25584909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 535, "text": "We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 942, "text": "Indeed, dupilumab prevents IL-4/13 interactions with the \u03b1-subunit of the IL-4 receptor complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 306, "text": "We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation could help in the treatment of related diseases, including atopic dermatitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 849, "text": "Indeed, dupilumab prevents IL-4/13 interactions with the \u03b1-subunit of the IL-4 receptor complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "endSection": "abstract" }, { "offsetInBeginSection": 51, "offsetInEndSection": 294, "text": "We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "endSection": "abstract" } ] }, { "body": "Which human genes are more commonly related to craniosynostosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12407713", "http://www.ncbi.nlm.nih.gov/pubmed/19530187", "http://www.ncbi.nlm.nih.gov/pubmed/16258006", "http://www.ncbi.nlm.nih.gov/pubmed/20643727", "http://www.ncbi.nlm.nih.gov/pubmed/10914960", "http://www.ncbi.nlm.nih.gov/pubmed/9934984", "http://www.ncbi.nlm.nih.gov/pubmed/18000908", "http://www.ncbi.nlm.nih.gov/pubmed/11428324", "http://www.ncbi.nlm.nih.gov/pubmed/17042739", "http://www.ncbi.nlm.nih.gov/pubmed/11746040", "http://www.ncbi.nlm.nih.gov/pubmed/17955513", "http://www.ncbi.nlm.nih.gov/pubmed/14672347", "http://www.ncbi.nlm.nih.gov/pubmed/10951518", "http://www.ncbi.nlm.nih.gov/pubmed/9917362", "http://www.ncbi.nlm.nih.gov/pubmed/15964893", "http://www.ncbi.nlm.nih.gov/pubmed/9042914", "http://www.ncbi.nlm.nih.gov/pubmed/11820058", "http://www.ncbi.nlm.nih.gov/pubmed/8106171", "http://www.ncbi.nlm.nih.gov/pubmed/9600744", "http://www.ncbi.nlm.nih.gov/pubmed/11484208", "http://www.ncbi.nlm.nih.gov/pubmed/11197897", "http://www.ncbi.nlm.nih.gov/pubmed/11341328" ], "ideal_answer": [ "The genes that are most commonly linked to craniosynostoses are the members of the Fibroblast Growth Factor Receptor family FGFR3 and to a lesser extent FGFR1 and FGFR2. Some variants of the disease have been associated with the triplication of the MSX2 gene and mutations in NELL-1. NELL-1 is being regulated bu RUNX2, which has also been associated to cases of craniosynostosis. Other genes reported to have a role in the development of the disease are RECQL4, TWIST, SOX6 and GNAS." ], "exact_answer": [ [ "FGFR3" ], [ "FGFR2" ], [ "FGFR1" ], [ "MSX2" ], [ "NELL1" ], [ "RUNX2" ], [ "RECQL4" ], [ "TWIST" ], [ "SOX6" ], [ "GNAS" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018566", "http://www.disease-ontology.org/api/metadata/DOID:2340", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003398" ], "type": "list", "id": "513ce3c8bee46bd34c000008", "snippets": [ { "offsetInBeginSection": 635, "offsetInEndSection": 721, "text": "The FGFR3 P250R mutation was the single largest contributor (24%) to the genetic group", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20643727", "endSection": "sections.0" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1521, "text": "FGFR3 P250R and FGFR2 exons IIIa/c) should be targeted to patients with coronal or multisuture synostoses", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20643727", "endSection": "sections.0" }, { "offsetInBeginSection": 602, "offsetInEndSection": 845, "text": "GNAS, the gene for guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (gene for PHP1A), identified a de novo heterozygous 3 bp in frame deletion predicting a deletion of the asparagine residue at position 377 (deltaN377", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19530187", "endSection": "sections.0" }, { "offsetInBeginSection": 924, "offsetInEndSection": 961, "text": "craniosynostosis genes (FGFR2, FGFR3)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19530187", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Syndromic craniosynostosis due to complex chromosome 5 rearrangement and MSX2 gene triplication", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000908", "endSection": "title" }, { "offsetInBeginSection": 782, "offsetInEndSection": 898, "text": "early fusion of cranial sutures commonly observed in the dup(5q) syndrome is caused by triplication of the MSX2 gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000908", "endSection": "sections.0" }, { "offsetInBeginSection": 52, "offsetInEndSection": 123, "text": "further evidence that extra copy of MSX2 gene leads to craniosynostosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17955513", "endSection": "title" }, { "offsetInBeginSection": 737, "offsetInEndSection": 903, "text": "Our results support the previous finding that distal 5q-trisomy together with an extra copy of the MSX2 gene leads to abnormal closure of sutures and craniosynostosis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17955513", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Craniosynostosis-associated gene nell-1 is regulated by runx2", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17042739", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 96, "text": "We studied the transcriptional regulation of NELL-1, a craniosynostosis-related gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17042739", "endSection": "sections.0" }, { "offsetInBeginSection": 2217, "offsetInEndSection": 2377, "text": "Runx2 directly binds to the OSE2 elements and transactivates the human NELL-1 promoter. These results suggest that Nell-1 is likely a downstream target of Runx2", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17042739", "endSection": "sections.0" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1035, "text": "The breakpoint on chromosome 11p15 disrupts the SOX6 gene, known to be involved in skeletal growth and differentiation processes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258006", "endSection": "sections.0" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1252, "text": "SOX6 mutation screening of another 104 craniosynostosis patients revealed one missense mutation leading to the exchange of a highly conserved amino acid (p.D68N) in a single patient and his reportedly healthy mother", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258006", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15964893", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Overexpression of Nell-1, a craniosynostosis-associated gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14672347", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 266, "text": "Mutations in five genes (FGFR1-, -2, -3, TWIST, and MSX2) causing craniosynostosis as the main clinical feature were described.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12407713", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "One of the genes involved in craniosynostosis syndromes is the fibroblast growth factor receptor 2 (FGFR2) gene, a tyrosine kinase receptor gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11820058", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Most mutations in Crouzon, Pfeiffer, and Apert syndromes are in the extracellular, third immunoglobulin-like domain and adjacent linker regions (exons IIIa and IIIc) of the fibroblast growth factor receptor 2 (FGFR2) gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11484208", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Familial craniosynostosis due to Pro250Arg mutation in the fibroblast growth factor receptor 3 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11428324", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Apert (Ap) syndrome is characterized by premature cranial suture ossification caused by fibroblast growth factor receptor 2 (FGFR-2) mutations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11341328", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Recently, the substitution of proline 250 by arginine in the fibroblast growth factor receptor 3 (FGFR3) gene, has been identified in patients with craniosynostosis and defines a new syndrome on a molecular basis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11197897", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Mutations in the fibroblast growth factor receptor 1, 2 and 3 (FGFR1, -2 and -3) and TWIST genes have been identified in several syndromic forms of craniosynostosis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10951518", "endSection": "sections.0" }, { "offsetInBeginSection": 303, "offsetInEndSection": 472, "text": "We describe a novel heterozygous mutation of FGFR2 (943G --> T, encoding the amino acid substitution Ala315Ser) in a girl with non-syndromic unicoronal craniosynostosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10951518", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A unique Pro250Arg mutation in fibroblast growth factor receptor 3 (FGFR3) was recently found in patients with non-syndromic craniosynostosis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10914960", "endSection": "sections.0" }, { "offsetInBeginSection": 123, "offsetInEndSection": 188, "text": "a possible mechanism for MSX2-mediated craniosynostosis in humans", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9917362", "endSection": "title" }, { "offsetInBeginSection": 532, "offsetInEndSection": 713, "text": "We found previously that a single amino acid substitution in the homeodomain of the human MSX2 gene is associated with the autosomal dominant disorder craniosynostosis, Boston type.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9917362", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Recently, a unique Pro250Arg point mutation in fibroblast growth factor receptor 3 (FGFR3) was reported in 61 individuals with coronal craniosynostosis from 20 unrelated families", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9600744", "endSection": "sections.0" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1409, "text": "We identified a novel TWIST gene mutation in this patient, a Glu181Stop mutation predicting a premature termination of the protein carboxy-terminal to the helix 2 domain", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9934984", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9042914", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8106171", "endSection": "title" } ] }, { "body": "Are transcribed ultraconserved regions involved in cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "http://www.ncbi.nlm.nih.gov/pubmed/21298224", "http://www.ncbi.nlm.nih.gov/pubmed/22617881", "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "http://www.ncbi.nlm.nih.gov/pubmed/24247010", "http://www.ncbi.nlm.nih.gov/pubmed/18323801", "http://www.ncbi.nlm.nih.gov/pubmed/20802525", "http://www.ncbi.nlm.nih.gov/pubmed/20383195" ], "ideal_answer": [ "Yes, it appears that there is widespread T-UCR (Transcribed - UltraConserved Region) involvement in diverse cellular processes that are deregulated in the process of tumourigenesis. Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "yesno", "id": "553f78c7ab98a37113000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "Although most cancer research has focused in mRNA, non-coding RNAs are also an essential player in tumorigenesis. In addition to the well-recognized microRNAs, recent studies have also shown that epigenetic silencing by CpG island hypermethylation of other classes of non-coding RNAs, such as transcribed ultraconserved regions (T-UCRs) or small nucleolar RNAs (snoRNAs), also occur in human neoplasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247010", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 684, "text": "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named 'hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1147, "text": "Consistent with the hypothesis that T-UCRs have important function in tumor formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 563, "text": "The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22617881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "endSection": "title" }, { "offsetInBeginSection": 105, "offsetInEndSection": 566, "text": "Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells. Genome-wide profiling revealed that T-UCRs have distinct signatures in human leukemia and carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1424, "text": " Our preliminary results suggest that uc.73 and uc.388 could be potential diagnostic and prognostic biomarkers in CRC patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The transcribed-ultraconserved regions: a novel class of long noncoding RNAs involved in cancer susceptibility", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21298224", "endSection": "title" }, { "offsetInBeginSection": 491, "offsetInEndSection": 906, "text": "This review gives a picture of the state of the art of a novel class of long ncRNA known as transcribed-ultraconserved regions (T-UCRs). Most recent studies show that they are significantly altered in adult chronic lymphocytic leukemias, carcinomas, and pediatric neuroblastomas, leading to the hypothesis that UCRs may play a role in tumorigenesis and promising innovative future T-UCR-based therapeutic approaches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21298224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20802525", "endSection": "title" }, { "offsetInBeginSection": 676, "offsetInEndSection": 1951, "text": "We focused on the transcribed-ultraconserved regions (T-UCRs), a subset of DNA sequences that are absolutely conserved between orthologous regions of the human, rat and mouse genomes and that are located in both intra- and intergenic regions. We used a pharmacological and genomic approach to reveal the possible existence of an aberrant epigenetic silencing pattern of T-UCRs by treating cancer cells with a DNA-demethylating agent followed by hybridization to an expression microarray containing these sequences. We observed that DNA hypomethylation induces release of T-UCR silencing in cancer cells. Among the T-UCRs that were reactivated upon drug treatment, Uc.160+, Uc283+A and Uc.346+ were found to undergo specific CpG island hypermethylation-associated silencing in cancer cells compared with normal tissues. The analysis of a large set of primary human tumors (n=283) demonstrated that hypermethylation of the described T-UCR CpG islands was a common event among the various tumor types. Our finding that, in addition to microRNAs, another class of ncRNAs (T-UCRs) undergoes DNA methylation-associated inactivation in transformed cells supports a model in which epigenetic and genetic alterations in coding and non-coding sequences cooperate in human tumorigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20802525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383195", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383195", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 969, "text": "our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383195", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 938, "text": "Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype. Here we review the main studies investigating the role of miRNAs and UCRs in both normal hemopoiesis and hematological malignancies, and identify the molecular, clinical and therapeutic implications of these recent findings", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18323801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The transcribed-ultraconserved regions: a novel class of long noncoding RNAs involved in cancer susceptibility.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21298224", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20802525", "endSection": "title" }, { "offsetInBeginSection": 220, "offsetInEndSection": 479, "text": "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 564, "text": "The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22617881", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 714, "text": "Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18323801", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 713, "text": "Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18323801", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 479, "text": "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "endSection": "abstract" } ] }, { "body": "In which breast cancer patients can palbociclib be used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25524798", "http://www.ncbi.nlm.nih.gov/pubmed/25792301", "http://www.ncbi.nlm.nih.gov/pubmed/26236140" ], "ideal_answer": [ "Palbociclib is useful for women with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer." ], "exact_answer": [ "hormone receptor-positive, human epidermal growth factor receptor 2-negative" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1612", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943" ], "type": "factoid", "id": "56d06e043975bb303a000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Women with hormone receptor-positive, human epidermal growth factor receptor 2- negative breast cancer-the most common subtype-have new options as palbociclib and similar drugs debut. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26236140", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 637, "text": "We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25524798", "endSection": "abstract" } ] }, { "body": "Do patients with Pendred syndrome present congenital deafness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15320950", "http://www.ncbi.nlm.nih.gov/pubmed/9070918", "http://www.ncbi.nlm.nih.gov/pubmed/10502702", "http://www.ncbi.nlm.nih.gov/pubmed/1810081", "http://www.ncbi.nlm.nih.gov/pubmed/10602116", "http://www.ncbi.nlm.nih.gov/pubmed/9398842", "http://www.ncbi.nlm.nih.gov/pubmed/21551164", "http://www.ncbi.nlm.nih.gov/pubmed/22717225", "http://www.ncbi.nlm.nih.gov/pubmed/8979104", "http://www.ncbi.nlm.nih.gov/pubmed/10443670", "http://www.ncbi.nlm.nih.gov/pubmed/9585042", "http://www.ncbi.nlm.nih.gov/pubmed/11375792", "http://www.ncbi.nlm.nih.gov/pubmed/21704276", "http://www.ncbi.nlm.nih.gov/pubmed/21274344", "http://www.ncbi.nlm.nih.gov/pubmed/18250610", "http://www.ncbi.nlm.nih.gov/pubmed/16924389", "http://www.ncbi.nlm.nih.gov/pubmed/22109890", "http://www.ncbi.nlm.nih.gov/pubmed/16482981", "http://www.ncbi.nlm.nih.gov/pubmed/10037079", "http://www.ncbi.nlm.nih.gov/pubmed/11716048", "http://www.ncbi.nlm.nih.gov/pubmed/8706311", "http://www.ncbi.nlm.nih.gov/pubmed/9920104", "http://www.ncbi.nlm.nih.gov/pubmed/8630498", "http://www.ncbi.nlm.nih.gov/pubmed/19318451", "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "http://www.ncbi.nlm.nih.gov/pubmed/8476169", "http://www.ncbi.nlm.nih.gov/pubmed/14727345", "http://www.ncbi.nlm.nih.gov/pubmed/23459462", "http://www.ncbi.nlm.nih.gov/pubmed/17299139" ], "ideal_answer": [ "Congenital deafness is one of the characteristics of Pendred syndrome patients." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003638" ], "type": "yesno", "id": "56d8b27651531f7e33000003", "snippets": [ { "offsetInBeginSection": 918, "offsetInEndSection": 1053, "text": "Pendred Syndrome can be characterized by the triad composed of familial goitre, abnormal perchlorate discharge and congenital deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14727345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Pendred syndrome comprises congenital sensorineural hearing loss, thyroid goiter, and positive perchlorate discharge test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10602116", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 548, "text": "The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8630498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Pendred syndrome is the autosomal recessively transmitted association of familial goiter and congenital deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Pendred syndrome (PDS) is an autosomal recessive disorder characterized by congenital deafness, goiter and iodide organification defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21274344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9398842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15320950", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1275, "text": "These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9398842", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 686, "text": "Mutations in the Pendred syndrome gene have been observed in patients with deafness and vestibular aqueduct dilatation, in the absence of other Pendred syndrome features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16482981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1810081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11375792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Pendred's syndrome is an autosomal recessive disease characterized by goiter, impaired iodide organification, and congenital sensorineural deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9920104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Pendred's syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8979104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Although the textbook view of the Pendred syndrome is that of an autosomal recessive condition characterised by deafness and goitre, it is increasingly clear that not all patients present this classical clinical description.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16482981", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 641, "text": "Pendred's syndrome may account for up to 10% of the cases with hereditary hearing loss, and pendrin mutations have also been found in a kindred with non-syndromic deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9920104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Pendred syndrome comprises the association of severe congenital sensorineural deafness with thyroid pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9585042", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 523, "text": "The first one is named Pendred Syndrome (PS) when deafness is associated with thyroid goiter; the second is called DFNB4, when no other symptoms are present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22717225", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, a partial defect in iodide organification, and dyshormonogenetic goiter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23459462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Pendred syndrome and non-syndromic recessive deafness associated with enlarged vestibular aqueduct (NSRD with EVA) are caused by mutations in the SLC26A4 (PDS) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16924389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1810081", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 406, "text": "The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8630498", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 482, "text": "The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9398842", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 374, "text": "Pendred's syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland. The majority of patients with Pendred's syndrome are euthyroid. We report on an unusual case of a patient with Pendred's syndrome presenting with amenorrhea and late-onset hypothyroidism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8979104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 528, "text": " Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. It has been estimated that 4-10 % of children with congenital deafness suffer from this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1810081", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 701, "text": "Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome. Since this is the most common radiological malformation of the cochlea in deaf patients, we investigated what proportion of such cases were due to mutation of the PDS gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 528, "text": "Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "endSection": "abstract" } ] }, { "body": "List side effects of SGLT2 inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25962253", "http://www.ncbi.nlm.nih.gov/pubmed/22977310", "http://www.ncbi.nlm.nih.gov/pubmed/24400675", "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "http://www.ncbi.nlm.nih.gov/pubmed/23807940", "http://www.ncbi.nlm.nih.gov/pubmed/24631482", "http://www.ncbi.nlm.nih.gov/pubmed/23042029", "http://www.ncbi.nlm.nih.gov/pubmed/24455799", "http://www.ncbi.nlm.nih.gov/pubmed/25488697", "http://www.ncbi.nlm.nih.gov/pubmed/24341330" ], "ideal_answer": [ "SGLT2 inhibitors can be associated with urogenital infections related to the enhanced glycosuria, and low blood pressure." ], "exact_answer": [ [ "urinary tract infections" ], [ "genital infections" ], [ "low blood pressure" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051297", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064420", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065606" ], "type": "list", "id": "571e1e11bb137a4b0c000004", "snippets": [ { "offsetInBeginSection": 515, "offsetInEndSection": 697, "text": "Due to side effects such as urinary tract and genital infections and decrease in blood pressure, proper patient selection for drug initiation and close monitoring will be important. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23807940", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1732, "text": "Urogenital side-effects related to the enhanced glycosuria can be troublesome, yet seldom lead to discontinuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 1019, "text": "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 1017, "text": "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Effect of SGLT2 inhibitors in a murine model of urinary tract infection with Candida albicans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24400675", "endSection": "title" }, { "offsetInBeginSection": 801, "offsetInEndSection": 975, "text": "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "endSection": "abstract" }, { "offsetInBeginSection": 1619, "offsetInEndSection": 1733, "text": "Urogenital side-effects related to the enhanced glycosuria can be troublesome, yet seldom lead to discontinuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 1019, "text": "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1348, "text": "There are some side effects that warrant further investigation and establishing whether SGLT2 inhibition provides a renal benefit relies on future long-term studies with specific renal end-points.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23042029", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1074, "text": "It should be noted that the currently approved agents have side effects that include an increased incidence of genital infections, predominantly in women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24631482", "endSection": "abstract" } ] }, { "body": "Is CD56 useful in Ewing sarcoma prognosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "http://www.ncbi.nlm.nih.gov/pubmed/9692823", "http://www.ncbi.nlm.nih.gov/pubmed/22498946" ], "ideal_answer": [ "Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometryIn patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)", "CD56 expression could be used to reveal Ewing sarcoma patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512" ], "type": "yesno", "id": "552fa32fbc4f83e828000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "title" }, { "offsetInBeginSection": 804, "offsetInEndSection": 986, "text": "There was a highly significant correlation between CD56 expression and progression-free survival (PFS; 69% in low/negative expression versus 30% in high expression groups, P = 0.024)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1132, "text": "In patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1305, "text": "CD56 was found to be an independent prognostic marker with an 11-fold increased risk for relapse in patients with localized disease (P = 0.006)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1654, "text": "CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "title" }, { "offsetInBeginSection": 530, "offsetInEndSection": 852, "text": "Three years after diagnosis the patient presented with severe respiratory difficulty and following resection, the final pathology revealed multiple tumors with foci of high grade sarcoma compatible with primitive neuroectodermal tumor/extraskeletal Ewing sarcoma based on morphology and immunohistochemistry (CD99, CD56).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22498946", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 336, "text": "CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Identification of CD56 and CD57 by flow cytometry in Ewing's sarcoma or primitive neuroectodermal tumor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9692823", "endSection": "title" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1607, "text": "CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "endSection": "abstract" } ] }, { "body": "What is the method FASP used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23603217", "http://www.ncbi.nlm.nih.gov/pubmed/22949036", "http://www.ncbi.nlm.nih.gov/pubmed/24051509", "http://www.ncbi.nlm.nih.gov/pubmed/24022122", "http://www.ncbi.nlm.nih.gov/pubmed/24288579", "http://www.ncbi.nlm.nih.gov/pubmed/23126408", "http://www.ncbi.nlm.nih.gov/pubmed/22324799", "http://www.ncbi.nlm.nih.gov/pubmed/23784971", "http://www.ncbi.nlm.nih.gov/pubmed/24289162", "http://www.ncbi.nlm.nih.gov/pubmed/23436586", "http://www.ncbi.nlm.nih.gov/pubmed/24309553", "http://www.ncbi.nlm.nih.gov/pubmed/23214492", "http://www.ncbi.nlm.nih.gov/pubmed/22092713" ], "ideal_answer": [ "Filter Aided Sample Preparation (FASP), a type of proteomic reactor, in which samples dissolved in sodium dodecyl sulfate (SDS) are digested in an ultrafiltration unit." ], "exact_answer": [ "proteomic sample preparation" ], "type": "factoid", "id": "5509f433c2af5d5b70000008", "snippets": [ { "offsetInBeginSection": 197, "offsetInEndSection": 236, "text": "FASP (filter-aided sample preparation) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309553", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 684, "text": "mouse brain tissue lysate was prepared using filter-aided sample preparation (FASP) method ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289162", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1047, "text": " an increased number of confident protein identifications are attained with a filter-aided digestion approach as compared to an in-solution digestion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24288579", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 897, "text": "filter-aided sample preparation (FASP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24051509", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 507, "text": "In the second step the isolated cells are lysed and processed using 'filter aided sample preparation' (FASP) technique. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24022122", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 914, "text": "filter-aided sample preparation (FASP),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23784971", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1135, "text": "filter assisted sample preparation (FASP) method", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603217", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 278, "text": "d filter-aided sample preparation (FASP)-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23436586", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 125, "text": " filter-aided sample preparation (FASP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23214492", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 438, "text": "filter-aided sample preparation (FASP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23126408", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 486, "text": "Filter Aided Sample Preparation (FASP), a type of proteomic reactor, in which samples dissolved in sodium dodecyl sulfate (SDS) are digested in an ultrafiltration unit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22324799", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 354, "text": " filter-aided sample preparation (FASP) protocol ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22092713", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 482, "text": "by combining a filter-aided sample preparation method a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22949036", "endSection": "abstract" } ] }, { "body": "What is the role of extracellular signal-related kinases 1 and 2 (ERK1/2) proteins in craniosynostosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23354439" ], "ideal_answer": [ "Reduced dosage of ERF, which encodes an inhibitory ETS transcription factor directly bound by ERK1/2 causes complex craniosynostosis (premature fusion of the cranial sutures) in humans and mice. Features of this newly recognized clinical disorder include multiple-suture synostosis, craniofacial dysmorphism, Chiari malformation and language delay." ], "concepts": [ "http://www.uniprot.org/uniprot/ERK1_CANAL", "http://www.disease-ontology.org/api/metadata/DOID:2340", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070371" ], "type": "summary", "id": "553fa2201d53b76422000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1/2 signaling to regulation of osteogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354439", "endSection": "title" }, { "offsetInBeginSection": 239, "offsetInEndSection": 793, "text": "we show that reduced dosage of ERF, which encodes an inhibitory ETS transcription factor directly bound by ERK1/2 (refs. 2,3,4,5,6,7), causes complex craniosynostosis (premature fusion of the cranial sutures) in humans and mice. Features of this newly recognized clinical disorder include multiple-suture synostosis, craniofacial dysmorphism, Chiari malformation and language delay. Mice with functional Erf levels reduced to \u223c30% of normal exhibit postnatal multiple-suture synostosis; by contrast, embryonic calvarial development appears mildly delayed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354439", "endSection": "abstract" } ] }, { "body": "Are there any urine biomarkers for chronic kidney disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20425065", "http://www.ncbi.nlm.nih.gov/pubmed/24315007", "http://www.ncbi.nlm.nih.gov/pubmed/24281781", "http://www.ncbi.nlm.nih.gov/pubmed/23758910", "http://www.ncbi.nlm.nih.gov/pubmed/21286212", "http://www.ncbi.nlm.nih.gov/pubmed/24065527", "http://www.ncbi.nlm.nih.gov/pubmed/23617441", "http://www.ncbi.nlm.nih.gov/pubmed/21151537", "http://www.ncbi.nlm.nih.gov/pubmed/23339563", "http://www.ncbi.nlm.nih.gov/pubmed/24133923", "http://www.ncbi.nlm.nih.gov/pubmed/24308223", "http://www.ncbi.nlm.nih.gov/pubmed/24224012", "http://www.ncbi.nlm.nih.gov/pubmed/24152229", "http://www.ncbi.nlm.nih.gov/pubmed/23344473", "http://www.ncbi.nlm.nih.gov/pubmed/22189039", "http://www.ncbi.nlm.nih.gov/pubmed/21538916", "http://www.ncbi.nlm.nih.gov/pubmed/23061738", "http://www.ncbi.nlm.nih.gov/pubmed/22914685", "http://www.ncbi.nlm.nih.gov/pubmed/21816077", "http://www.ncbi.nlm.nih.gov/pubmed/24205707" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/keyword/CHRONIC+DISEASE%2Furine", "o": "CHRONIC DISEASE/urine" } ], "ideal_answer": [ "Chronic kidney disease (CKD), is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia or pericarditis. It is differentiated from acute kidney disease in that the reduction in kidney function must be present for over 3 months.", "Yes, there is a number of urine biomarkers used for early detection of chronic kidney disease." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:784", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002678", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012079", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007674", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002676", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002677", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007672", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014556", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014554", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007676", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.disease-ontology.org/api/metadata/DOID:3265", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002544", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002908", "http://www.disease-ontology.org/api/metadata/DOID:2975", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051437", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051436", "http://www.disease-ontology.org/api/metadata/DOID:557", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003928", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007668", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054316" ], "type": "yesno", "id": "52fa73c62059c6d71c000058", "snippets": [ { "offsetInBeginSection": 485, "offsetInEndSection": 726, "text": "Kidney and urine proteomic biomarkers are considered as promising diagnostic tools to predict CKD progression early in diabetic nephropathy, facilitating timely and selective intervention that may reduce the related health-care expenditures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21538916", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 1028, "text": "Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21286212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21286212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "There is a strong association between both acute and chronic dysfunction of the heart and kidneys with respect to morbidity and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151537", "endSection": "abstract" }, { "offsetInBeginSection": 1265, "offsetInEndSection": 1452, "text": "Both blood and urine biomarkers, including the assessment of catalytic iron, a critical element to the generation of oxygen-free radicals and oxidative stress, are reviewed in this paper.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151537", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 1225, "text": "Identification of urine biomarkers has proven to be beneficial in recent years because of ease of handling, stability, and the ability to standardize the various markers to creatinine or other peptides generally already present in the urine. Recent markers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and podocin have garnered a lot of attention. The emergence of these and other biomarkers is largely because of the evolution of novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20425065", "endSection": "abstract" } ] }, { "body": "What is being measured with an accelerometer in back pain patients", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23865908", "http://www.ncbi.nlm.nih.gov/pubmed/18752975", "http://www.ncbi.nlm.nih.gov/pubmed/19945891", "http://www.ncbi.nlm.nih.gov/pubmed/16426878", "http://www.ncbi.nlm.nih.gov/pubmed/15271728", "http://www.ncbi.nlm.nih.gov/pubmed/21872993", "http://www.ncbi.nlm.nih.gov/pubmed/21195646", "http://www.ncbi.nlm.nih.gov/pubmed/23560880", "http://www.ncbi.nlm.nih.gov/pubmed/19895697", "http://www.ncbi.nlm.nih.gov/pubmed/16437292", "http://www.ncbi.nlm.nih.gov/pubmed/20921030", "http://www.ncbi.nlm.nih.gov/pubmed/11387574", 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"s": "http://linkedlifedata.com/resource/umls/id/C0178951", "o": "http://linkedlifedata.com/resource/umls/relation/R55686825" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R112090206", "o": "http://linkedlifedata.com/resource/umls/id/C0178951" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R55854007", "o": "http://linkedlifedata.com/resource/umls/id/C0178951" }, { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/umls/id/C0178951", "o": "UMD: Devices designed to measure the rate of change of an object's velocity. These devices typically consist of a sensor and transducer, an amplifier, and extension cables for connection to an electronic measuring unit. They work on the principle of seismic mass: this mass is restrained by a spring, and when the transducer case is accelerated, the mass moves relative to the case and exerts a force on the spring. The acceleration is calculated by measuring mass displacement or the mass' force on the spring, converted to an electrical signal. Acceleration transducers are available using strain gauges (e.g., metallic foil, piezoresistive), capacitive elements, and piezoelectric elements. Clinical accelerometers are intended for several purposes, including measuring the acceleration of body parts to assess a patient's mobility and/or activity (alone or as a component of activity monitors and gait analyzers respectively); assess tremor (e.g., in patients with Parkinson's disease); and activate pacemakers according" } ], "ideal_answer": [ "Accelerometer assessment measuring overall physical activity (PAL), constant strain postures (CSP), standing time (ST) and lying time (LT)...\nThe following parameters of physical activity were recorded: time upright (standing or walking), time standing, time walking, and step count." ], "exact_answer": [ [ "Physical activity", "PA", "PAL" ], [ "Constant Strain Postures", "CSP", "constant postures" ], [ "Standing time", "ST" ], [ "Lying time", "LT" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013001", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059787", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001416", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010146", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019567", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059350", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017116", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018710" ], "type": "list", "id": "533f9df0c45e133714000016", "snippets": [ { "offsetInBeginSection": 373, "offsetInEndSection": 511, "text": "accelerometer assessment measuring overall physical activity (PAL), constant strain postures (CSP), standing time (ST) and lying time (LT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23865908", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 790, "text": "Physical activity was measured for 7 days at both baseline and at 3 months with an RT3 accelerometer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560880", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 600, "text": "wearing an accelerometer to assess physical activity in daily life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21872993", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 659, "text": "An accelerometer was used to objectively assess their activity level ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21195646", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 581, "text": "objective activity data to determine whether patients with chronic lower back pain report their activity levels as accurately as controls do. DESIGN: A cross-sectional study was performed in patients and controls. SETTING: The study was carried out in the daily environment of the subjects. SUBJECTS: Thirty-two chronic lower back pain patients with symptoms more than three months and 20 healthy controls from the Netherlands, aged 18-65 years. MAIN MEASURES: A tri-axial accelerometer was worn for five weekdays", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921030", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 666, "text": "During 14days physical activity in daily life was measured, with both an electronic diary and an accelerometer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20457489", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 920, "text": "physical activity in daily life was measured with an accelerometer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19945891", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 539, "text": "physical activity (PA) in individuals with chronic low back pain (CLBP). Thirty-eight participants with non-specific CLBP (29=distressed; 9=non-distressed) were recruited. PA levels were measured using an accelerometer (activPAL activity monitor) over a one week period. The following parameters of physical activity were recorded: time upright (standing or walking), time standing, time walking, and step count.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19945334", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 866, "text": "Physical activity levels will be measured by self report, RT3 triaxial accelerometer,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19895697", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 452, "text": "to study the time spent in different static trunk postures which was recorded by a biaxial accelerometer attached to the T12 level", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19402888", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 538, "text": "Daily activities were assessed by measuring body movement with a tri-axial accelerometer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18752975", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 556, "text": "nighttime activity data from 18 patients diagnosed with chronic back pain. The patients were followed for 6 days and 5 nights. Pain levels were collected every 90 min between 0800 hours and 2,200 hours using a computerized electronic diary. Activity levels were collected using a wrist accelerometer (Actiwatch AW-64). The Actiwatch sampled activity counts every 1 min. Patients were asked to wear the Actiwatch on their non-dominant arm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16437292", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 884, "text": " 8-h accelerometer assessment in their daily life (physical activity level (PAL), number of constant postures (CP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426878", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 321, "text": "The activity levels were collected automatically using a wrist accelerometer and were sampled every minute.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15271728", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 691, "text": "Physical activity in daily life, expressed as whole-body acceleration measured with a triaxial accelerometer (Tracmor),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11387574", "endSection": "abstract" } ] }, { "body": "List the releases of JASPAR database", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16381983", "http://www.ncbi.nlm.nih.gov/pubmed/14681366", "http://www.ncbi.nlm.nih.gov/pubmed/24194598", "http://www.ncbi.nlm.nih.gov/pubmed/19906716", "http://www.ncbi.nlm.nih.gov/pubmed/18006571" ], "ideal_answer": [ "JASPAR, JASPAR CORE, JASPAR FAM, JASPAR phyloFACTS, JASPAR 2008 update, JASPAR 2010, JASPAR 2014." ], "exact_answer": [ [ "JASPAR" ], [ "JASPAR CORE" ], [ "JASPAR FAM" ], [ "JASPAR phyloFACTS" ], [ "JASPAR 2008 update" ], [ "JASPAR 2010" ], [ "JASPAR 2014" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ], "type": "list", "id": "56a3a386496b62f23f000007", "snippets": [ { "offsetInBeginSection": 276, "offsetInEndSection": 789, "text": "JASPAR is an open-access database of annotated, high-quality, matrix-based transcription factor binding site profiles for multicellular eukaryotes. The profiles were derived exclusively from sets of nucleotide sequences experimentally demonstrated to bind transcription factors. The database is complemented by a web interface for browsing, searching and subset selection, an online sequence analysis utility and a suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 750, "text": "JASPAR is the most complete open-access collection of transcription factor binding site (TFBS) matrices. In this new release, JASPAR grows into a meta-database of collections of TFBS models derived by diverse approaches. We present JASPAR CORE--an expanded version of the original, non-redundant collection of annotated, high-quality matrix-based transcription factor binding profiles, JASPAR FAM--a collection of familial TFBS models and JASPAR phyloFACTS--a set of matrices computationally derived from statistically overrepresented, evolutionarily conserved regulatory region motifs from mammalian genomes. JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19906716", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194598", "endSection": "title" }, { "offsetInBeginSection": 189, "offsetInEndSection": 1037, "text": "The fifth major release greatly expands the heart of JASPAR-the JASPAR CORE subcollection, which contains curated, non-redundant profiles-with 135 new curated profiles (74 in vertebrates, 8 in Drosophila melanogaster, 10 in Caenorhabditis elegans and 43 in Arabidopsis thaliana; a 30% increase in total) and 43 older updated profiles (36 in vertebrates, 3 in D. melanogaster and 4 in A. thaliana; a 9% update in total). The new and updated profiles are mainly derived from published chromatin immunoprecipitation-seq experimental datasets. In addition, the web interface has been enhanced with advanced capabilities in browsing, searching and subsetting. Finally, the new JASPAR release is accompanied by a new BioPython package, a new R tool package and a new R/Bioconductor data package to facilitate access for both manual and automated methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194598", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006571", "endSection": "title" }, { "offsetInBeginSection": 106, "offsetInEndSection": 610, "text": "In this new release, JASPAR grows into a meta-database of collections of TFBS models derived by diverse approaches. We present JASPAR CORE--an expanded version of the original, non-redundant collection of annotated, high-quality matrix-based transcription factor binding profiles, JASPAR FAM--a collection of familial TFBS models and JASPAR phyloFACTS--a set of matrices computationally derived from statistically overrepresented, evolutionarily conserved regulatory region motifs from mammalian genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381983", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 824, "text": "JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis. The new release of JASPAR is available at http://jaspar.genereg.net. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381983", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 809, "text": "JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis. The new release of JASPAR is available at http://jaspar.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381983", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 821, "text": "JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis. The new release of JASPAR is available at http://jaspar.genereg.net.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381983", "endSection": "abstract" } ] }, { "body": "List symptoms of the IFAP syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10398262", "http://www.ncbi.nlm.nih.gov/pubmed/1915513", "http://www.ncbi.nlm.nih.gov/pubmed/19689518", "http://www.ncbi.nlm.nih.gov/pubmed/21886760", "http://www.ncbi.nlm.nih.gov/pubmed/14708109", "http://www.ncbi.nlm.nih.gov/pubmed/15370546", "http://www.ncbi.nlm.nih.gov/pubmed/25685152", "http://www.ncbi.nlm.nih.gov/pubmed/10694306", "http://www.ncbi.nlm.nih.gov/pubmed/16268889", "http://www.ncbi.nlm.nih.gov/pubmed/10326971", "http://www.ncbi.nlm.nih.gov/pubmed/21315478", "http://www.ncbi.nlm.nih.gov/pubmed/12004300", "http://www.ncbi.nlm.nih.gov/pubmed/1456297", "http://www.ncbi.nlm.nih.gov/pubmed/24090718", "http://www.ncbi.nlm.nih.gov/pubmed/24313295" ], "ideal_answer": [ "The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia." ], "exact_answer": [ [ "follicular ichthyosis" ], [ "atrichia" ], [ "photophobia" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "list", "id": "56c1f038ef6e394741000051", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 147, "text": "The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 846, "text": "Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum of X-linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and photophobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia) syndrome, keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) and an X-linked form of Olmsted syndrome. We report a recurrent intronic mutation in MBTPS2 (c.671-9T>G) in a Chinese patient with the typical triad of IFAP syndrome (i.e. ichthyosis, atrichia and photophobia), along with pachyonychia, palmoplantar and periorificial keratoderma, which were reminiscent of Olmsted syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24313295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090718", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 850, "text": "This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090718", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 787, "text": "The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia, recurrent respiratory infections, etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1456297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Photoletter to the editor: A new variant of ichthyosis follicularis with alopecia and photophobia (IFAP) syndrome with coexisting psoriasiform lesions and palmoplantar keratoderma. IFAP-PPK syndrome?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21886760", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Ichthyosis follicularis, atrichia, and photophobia (IFAP) are typical features of a rare neuroichthyosis termed IFAP syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10326971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Child with manifestations of dermotrichic syndrome and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1456297", "endSection": "title" }, { "offsetInBeginSection": 352, "offsetInEndSection": 448, "text": "These features correspond to the ichthyosis follicularis, alopecia, photophobia (IFAP) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14708109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome is a rare congenital disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21315478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome in two unrelated female patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12004300", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Linear lesions reflecting lyonization in women heterozygous for IFAP syndrome (ichthyosis follicularis with atrichia and photophobia).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10398262", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome due to mutation of the gene MBTPS2 in a large Australian kindred.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19689518", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome treated with acitretin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16268889", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Atrichia, ichthyosis, follicular hyperkeratosis, chronic candidiasis, keratitis, seizures, mental retardation and inguinal hernia: a severe manifestation of IFAP syndrome?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10694306", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Ocular findings in ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15370546", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "We describe an 18-month-old male infant suffering from the ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome and further delineate the clinical phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1915513", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 739, "text": "The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia, recurrent respiratory infections, etc.), those that are present only in dermotrichic syndrome (nail anomalies, hypohydrosis, megacolon, vertebral defects, etc.) and additional ones (enamel dysplasia, renal anomalies, inguinal hernia, etc.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1456297", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 499, "text": "The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1456297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Ichthyosis follicularis, atrichia, and photophobia (IFAP) are typical features of a rare neuroichthyosis termed IFAP syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10326971", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 354, "text": "These features correspond to the ichthyosis follicularis, alopecia, photophobia (IFAP) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14708109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome is a rare congenital disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21315478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090718", "endSection": "abstract" } ] }, { "body": "Which gene is required for the efficient function of clopidogrel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23150151", "http://www.ncbi.nlm.nih.gov/pubmed/23506580", "http://www.ncbi.nlm.nih.gov/pubmed/15933261", "http://www.ncbi.nlm.nih.gov/pubmed/21099121", "http://www.ncbi.nlm.nih.gov/pubmed/19463375", "http://www.ncbi.nlm.nih.gov/pubmed/20826260", "http://www.ncbi.nlm.nih.gov/pubmed/21806387" ], "ideal_answer": [ "The prodrug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 CYP2C19), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients" ], "exact_answer": [ "cytochrome P450, CYPC19" ], "concepts": [ "http://www.biosemantics.org/jochem#4275944", "http://www.biosemantics.org/jochem#4260620", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "factoid", "id": "531a34d5b166e2b806000036", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 104, "text": "The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23506580", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 380, "text": "This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23506580", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 87, "text": "ssociation of a functional polymorphism in the clopidogrel target receptor gene, P2Y12", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15933261", "endSection": "title" }, { "offsetInBeginSection": 129, "offsetInEndSection": 330, "text": "We tested for an association of gene sequence variations in P2Y12 and occurrence of neurological adverse events in patients with symptomatic peripheral artery disease (PAD) during clopidogrel treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15933261", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 377, "text": "Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463375", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 831, "text": "Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463375", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 117, "text": "The prodrug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes for its antiplatelet effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20826260", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1558, "text": "Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463375", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 945, "text": "Carriers of the CYP2C19*17 T-allele, with increased clopidogrel activation, had a 37% relative reduction in the TLR incidence, the primary end point", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20826260", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "The cytochrome P450 (CYP) 2C19*2 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after stent implantation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21099121", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1624, "text": "From these results it is suggested that CYP2C19*2 polymorphism is associated with subclinical thrombus formation among Japanese patients receiving clopidogrel. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21099121", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 457, "text": "To determine the effect of various SNPs on post-clopidogrel platelet reactivity and clinical outcome. MATERIALS & METHODS: Cytochrome 2C19 (CYP2C19) loss-of-function (LOF; *2, *3) and gain-of-function (GOF; *17) allelic variants, together with ABCB1 (3435 C\u2192T and 2677 G\u2192T/A) and paraoxonase-1 (PON-1; 192 Q\u2192R) SNPs were analyzed in 189 patients after elective stent implantation who participated in a randomized, placebo-controlled trial (NCT00638326)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21806387", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 126, "text": "Chinese people are more frequent carriers of cytochrome P450 2C19 (CYP2C19) loss-of-function alleles than Caucasians.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150151", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 555, "text": "The aim of this study was to investigate the effect of the CYP2C19, ABCB1, and PON1 variants on clopidogrel pharmacodynamics and clinical outcomes in these patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150151", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1344, "text": "The risk of a low response to clopidogrel and composite ischemic events increased with the number of CYP2C19 loss-of-function alleles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150151", "endSection": "abstract" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1582, "text": "However, there were not significant differences in clopidogrel pharmacodynamics and clinical outcomes across the ABCB1 and PON1 genotype groups; bleeding was not significantly different across the CYP2C19, ABCB1, and PON1 genotype groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150151", "endSection": "abstract" }, { "offsetInBeginSection": 1597, "offsetInEndSection": 1894, "text": "The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150151", "endSection": "abstract" } ] }, { "body": "Is valproic acid effective for glioblastoma treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "http://www.ncbi.nlm.nih.gov/pubmed/24874578", "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "http://www.ncbi.nlm.nih.gov/pubmed/23680820", "http://www.ncbi.nlm.nih.gov/pubmed/24899645", "http://www.ncbi.nlm.nih.gov/pubmed/23523186" ], "ideal_answer": [ "Yes, valproic acid prolong survival of glioblastoma patients. Valproic acid is an antiepileptic agent with histone deacetylase inhibitor activity shown to sensitize glioblastoma cells to radiation in preclinical models." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014635", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005909", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4271063", "http://www.biosemantics.org/jochem#4271063" ], "type": "yesno", "id": "56c1f029ef6e39474100004a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "PURPOSE: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "endSection": "abstract" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1377, "text": " Median overall survival (OS) was 29.6\u00a0months (range: 21-63.8\u00a0months), and median progression-free survival (PFS) was 10.5\u00a0months (range: 6.8-51.2\u00a0months). OS at 6, 12, and 24\u00a0months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24\u00a0months was 70%, 43%, and 38% respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1955, "text": "CONCLUSIONS: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1394, "text": "Treatment of GDSCs with histone deacetylase inhibitors, TSA and VPA, significantly reduced proliferation rates of the cells and expression of the stem cell markers, indicating differentiation of the cells. Since differentiation into GBM makes them susceptible to the conventional cancer treatments, we posit that use of histone deacetylase inhibitors may increase efficacy of the conventional cancer treatments for eliminating GDSCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24874578", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 346, "text": "Several clinical studies have reported that valproic acid could prolong survival of GBM patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1327, "text": "Our meta-analysis confirmed the benefit of using VPA (HR, 0.56; 95% CI, 0.44-0.71). Sub-group analysis shows that patients treated with VPA had a hazard ratio of 0.74 with a 95% confidence interval of 0.59-0.94 vs. patients treated by other-AEDs and a hazard ratio of 0.66 with a 95% confidence interval of 0.52-0.84 vs. patients treated by administration of non-AEDs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1513, "text": ".CONCLUSION: The results of our study suggest that glioblastoma patients may experience prolonged survival due to VPA administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1453, "text": "A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24899645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Valproic acid use during radiation therapy for glioblastoma associated with improved survival", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523186", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Valproic acid use during radiation therapy for glioblastoma associated with improved survival.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523186", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 772, "text": "PURPOSE: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS).METHODS AND MATERIALS: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS.RESULTS: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523186", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 820, "text": "When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), independently of RTOG RPA class and seizure history.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523186", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 850, "text": "Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23680820", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 225, "text": "Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23680820", "endSection": "abstract" } ] }, { "body": "Which transcription factor is considered as a master regulator of lysosomal genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23457305", "http://www.ncbi.nlm.nih.gov/pubmed/25315655", "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "http://www.ncbi.nlm.nih.gov/pubmed/21752829", "http://www.ncbi.nlm.nih.gov/pubmed/25750174", "http://www.ncbi.nlm.nih.gov/pubmed/23830905", "http://www.ncbi.nlm.nih.gov/pubmed/25605940", "http://www.ncbi.nlm.nih.gov/pubmed/21804531", "http://www.ncbi.nlm.nih.gov/pubmed/23604321", "http://www.ncbi.nlm.nih.gov/pubmed/23524842", "http://www.ncbi.nlm.nih.gov/pubmed/21617040", "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "http://www.ncbi.nlm.nih.gov/pubmed/23609508", "http://www.ncbi.nlm.nih.gov/pubmed/25060788", "http://www.ncbi.nlm.nih.gov/pubmed/23393155" ], "ideal_answer": [ "Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy, driving lysosome adaptation to environmental cues, such as starvation, and therefore targeting of TFEB may provide a novel therapeutic strategy for modulating lysosomal function in human disease." ], "exact_answer": [ "Transcription factor EB (TFEB)" ], "type": "factoid", "id": "56cdf40d5795f9a73e00003d", "snippets": [ { "offsetInBeginSection": 252, "offsetInEndSection": 424, "text": "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 584, "text": "Interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to mTORC1-dependent phosphorylation and inhibition of TFEB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 868, "text": "Depletion or inactivation of Rags prevented recruitment of TFEB to lysosomes, whereas expression of active Rags induced association of TFEB with lysosomal membranes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 874, "text": "The identification of a master regulator, transcription factor EB (TFEB), that regulates lysosomal biogenesis and autophagy has revealed how the lysosome adapts to environmental cues, such as starvation, and targeting TFEB may provide a novel therapeutic strategy for modulating lysosomal function in human disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23609508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 37, "text": "TFEB regulates lysosomal proteostasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "title" }, { "offsetInBeginSection": 763, "offsetInEndSection": 933, "text": "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "abstract" }, { "offsetInBeginSection": 1648, "offsetInEndSection": 1724, "text": "our findings identify TFEB as a specific regulator of lysosomal proteostasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 483, "text": "the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23604321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 414, "text": "the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1201, "text": "the lysosome senses its content and regulates its own biogenesis by a lysosome-to-nucleus signalling mechanism that involves TFEB and mTOR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1189, "text": "These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21804531", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 867, "text": "We showed that the mouse GRN gene has two possible coordinated lysosomal expression and regulation (CLEAR) sequences that bind to transcription factor EB (TFEB), a master regulator of lysosomal genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830905", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 596, "text": "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 606, "text": "In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23524842", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 603, "text": "Here, we show that the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "abstract" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1100, "text": "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 771, "text": "Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc1\u03b1 and Ppar1\u03b1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23604321", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 835, "text": "Transcription factor EB, a master regulator of lysosomal biogenesis, also negatively regulated HIF-1 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23457305", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1345, "text": "These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21804531", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1330, "text": "We found that ceria nanoparticles promote activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and induce upregulation of genes of the lysosome-autophagy system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315655", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 558, "text": "The transcription factor EB (TFEB), a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21617040", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 443, "text": "In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23524842", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 671, "text": "We showed that the mouse GRN gene has two possible coordinated lysosomal expression and regulation (CLEAR) sequences that bind to transcription factor EB (TFEB), a master regulator of lysosomal genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830905", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 426, "text": "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 517, "text": "We recently discovered the CLEAR (Coordinated Lysosomal Expression and Regulation) gene network and its master gene transcription factor EB (TFEB), which regulates lysosomal biogenesis and function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752829", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1251, "text": "Transcription factor EB (TFEB) is the only known transcription factor that is a master regulator of lysosomal biogenesis although its role in macrophages has not been studied. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25060788", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 532, "text": "In contrast to its classical function as the waste management machinery, lysosomes are now considered to be an integral part of various cellular signaling processes. The diverse functionality of this single organelle requires a very complex and coordinated regulation of its activity with transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, at its core.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25750174", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 416, "text": "Here, we show that the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 671, "text": "We showed that the mouse GRN gene has two possible coordinated lysosomal expression and regulation (CLEAR) sequences that bind to transcription factor EB (TFEB), a master regulator of lysosomal genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830905", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 426, "text": "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 509, "text": "We observed that the MiT family of transcription factors, which includes the melanoma oncogene MITF (micropthalmia-associated transcription factor) and the lysosomal master regulator TFEB, had the highest phylogenetic conservation of three consecutive putative GSK3 phosphorylation sites in animal proteomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25605940", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 730, "text": "Transcription factor EB, a master regulator of lysosomal biogenesis, also negatively regulated HIF-1 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23457305", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 940, "text": "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "abstract" }, { "offsetInBeginSection": 1044, "offsetInEndSection": 1219, "text": "Transcription factor EB (TFEB) is the only known transcription factor that is a master regulator of lysosomal biogenesis although its role in macrophages has not been studied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25060788", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1190, "text": "These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21804531", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 443, "text": "In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23524842", "endSection": "abstract" } ] }, { "body": "Which antibiotics target peptidoglycan biosynthesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9210483", "http://www.ncbi.nlm.nih.gov/pubmed/10801476", "http://www.ncbi.nlm.nih.gov/pubmed/12440876", "http://www.ncbi.nlm.nih.gov/pubmed/12197711", "http://www.ncbi.nlm.nih.gov/pubmed/22280885", "http://www.ncbi.nlm.nih.gov/pubmed/8891144", "http://www.ncbi.nlm.nih.gov/pubmed/21867549", "http://www.ncbi.nlm.nih.gov/pubmed/11751110", "http://www.ncbi.nlm.nih.gov/pubmed/2334153", "http://www.ncbi.nlm.nih.gov/pubmed/7590155", "http://www.ncbi.nlm.nih.gov/pubmed/25224006", "http://www.ncbi.nlm.nih.gov/pubmed/20515462", "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "http://www.ncbi.nlm.nih.gov/pubmed/18558445", "http://www.ncbi.nlm.nih.gov/pubmed/21091161", "http://www.ncbi.nlm.nih.gov/pubmed/22815801", "http://www.ncbi.nlm.nih.gov/pubmed/16832063" ], "ideal_answer": [ "Under some conditions, both ramoplanin and vancomycin probes produce helicoid staining patterns along the cylindrical walls of B. subtilis cells. This work has implications for the design of ramoplanin derivatives and may influence how other proposed substrate binding antibiotics are studied. This was confirmed by in vitro studies involving a wall-membrane particulate fraction from Gaffkya homari in which peptidoglycan synthesis from UDP-MurNAc-tetrapeptide was inhibited by ramoplanin but not by vancomycin. New results support a two-state model for septal and peripheral PG synthesis at mid-cell, involvement of essential cell division proteins in PG remodeling, and mid-cell localization of proteins that organize PG biosynthesis and that form the protein translocation apparatus.", "Antibiotics which inhibit bacterial peptidoglycan biosynthesis are the most widely used in current clinical practice. Cells treated with ampicillin, D-cycloserine, or fosfomycin had only one chloroplast after cell division, suggesting that the cells divided without chloroplast division. The antibiotics bacitracin and vancomycin showed no obvious effect. Colchicine inhibits Closterium cell elongation after division. Surprisingly, also cinnamycin of Streptomyces cinnamoneus cinnamoneus), previously known to bind specifically to phosphatidylethanolamin of biological membranes, provoked strong cell wall biosynthetic stress. Other substances include fluorescent derivatives of two PG-binding antibiotics, vancomycin and ramoplanin. The muraymycins constitute a new antibiotic family whose core structure contains a glycosylated uronic acid derivative joined by an aminopropane group to a hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing dipeptide that is further extended by a urea-valine moiety. The muraymycins inhibited peptidoglycan biosynthesis. Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis. The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation. Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria." ], "exact_answer": [ [ "colchicine" ], [ "fosfomycin" ], [ "bacitracin" ], [ "vancomycin" ], [ "D-cycloserine", "seromycin" ], [ "ampicillin" ], [ "cinnamycin" ], [ "ramoplanin" ], [ "muraymycin" ], [ "mersacidin" ] ], "type": "list", "id": "571529efcb4ef8864c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Treatment with antibiotics that interfere with peptidoglycan biosynthesis inhibits chloroplast division in the desmid Closterium", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815801", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 360, "text": "To detect cells just after division, we used colchicine, which inhibits Closterium cell elongation after division", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815801", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 685, "text": "The antibiotics bacitracin and vancomycin showed no obvious effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815801", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 616, "text": "cells treated with ampicillin, D-cycloserine, or fosfomycin had only one chloroplast after cell division, suggesting that the cells divided without chloroplast division", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815801", "endSection": "abstract" }, { "offsetInBeginSection": 67, "offsetInEndSection": 245, "text": "We investigated the effects of antibiotics that interfere with peptidoglycan biosynthesis on chloroplast division in the desmid Closterium peracerosum-strigosum-littorale complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Recent advances in pneumococcal peptidoglycan biosynthesis suggest new vaccine and antimicrobial targets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22280885", "endSection": "title" }, { "offsetInBeginSection": 418, "offsetInEndSection": 657, "text": "Of late, the peptidoglycan (PG) layer, the most important component of the bacterial cell wall has been the subject of drug targeting because, first, it is essential for the survivability of eubacteria and secondly, it is absent in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21091161", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 129, "text": "Antibiotics which inhibit bacterial peptidoglycan biosynthesis are the most widely used in current clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867549", "endSection": "abstract" }, { "offsetInBeginSection": 1587, "offsetInEndSection": 1710, "text": "A dose-response experiment with an E. coli strain susceptible to ampicillin demonstrated a weak effect before the MIC dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867549", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1408, "text": " In an initial approach, the procedure accurately discriminates susceptible, intermediate and resistant strains of Escherichia coli to amoxicillin/clavulanic acid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21867549", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1255, "text": "Surprisingly, also cinnamycin of Streptomyces cinnamoneus cinnamoneus), previously known to bind specifically to phosphatidylethanolamin of biological membranes, provoked strong cell wall biosynthetic stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18558445", "endSection": "abstract" }, { "offsetInBeginSection": 571, "offsetInEndSection": 727, "text": "Here, we compare the staining patterns observed in Bacillus subtilis using fluorescent derivatives of two PG-binding antibiotics, vancomycin and ramoplanin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16832063", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1061, "text": "Ramoplanin probes may be better imaging agents than vancomycin probes because they yield clear staining patterns at concentrations well below their minimum inhibitory concentrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16832063", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Structures of the muraymycins, novel peptidoglycan biosynthesis inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12197711", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 605, "text": "The muraymycins constitute a new antibiotic family whose core structure contains a glycosylated uronic acid derivative joined by an aminopropane group to a hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing dipeptide that is further extended by a urea-valine moiety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12197711", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 796, "text": "The muraymycins inhibited peptidoglycan biosynthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12197711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Rethinking ramoplanin: the role of substrate binding in inhibition of peptidoglycan biosynthesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12440876", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12440876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Vancomycin binds to bacterial cell-wall intermediates to achieve its antibiotic effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10801476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9210483", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The lantibiotic mersacidin has been previously reported to interfere with bacterial peptidoglycan biosynthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9210483", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 454, "text": "Here, we focus on the target reaction and describe a mersacidin-induced accumulation of UDP-N-acetylmuramoyl-pentapeptide, indicating that inhibition of peptidoglycan synthesis occurs after the formation of cytoplasmic precursors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9210483", "endSection": "abstract" }, { "offsetInBeginSection": 1099, "offsetInEndSection": 1430, "text": "The analogy to the glycopeptides may hint at an interaction of mersacidin with the peptidoglycan precursor rather than with the enzyme. Unlike vancomycin however, mersacidin inhibits peptidoglycan formation from UDP-N-acetylmuramoyl-tripeptide and is active against Enterococcus faecium expressing the vanA resistance gene cluster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9210483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8891144", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "LY191145 is a p-chlorobenzyl derivative of LY264826 (A82846B) with activity against both vancomycin-susceptible and -resistant enterococci. Incorporation of L-[14C]lysine into peptidoglycan of intact vancomycin-susceptible and -resistant Enterococcus faecium was inhibited by LY191145 (50% inhibitory concentrations of 1 and 5 microgram/ml, respectively). Inhibition was accompanied by accumulation of UDP-muramyl-peptide precursors in the cytoplasm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8891144", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1397, "text": "The fact that inhibition of peptidoglycan biosynthesis by LY191145 was not readily antagonized by an excess of free acyl-D-alanyl-D-alanine or acyl-D-alanyl-D-lactate ligands indicates that the manner in which this compound inhibits transglycosylation may not be identical to that of vancomycin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8891144", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 980, "text": "Comparison with tunicamycin-treated cells indicated that peptidoglycan rather than teichoic acid metabolism is primarily affected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1076, "text": "Mersacidin caused the excretion of a putative cell wall precursor into the culture supernatant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Mersacidin is an antibiotic peptide produced by Bacillus sp. strain HIL Y-85,54728 that belongs to the group of lantibiotics. Its activity in vivo against methicillin-resistant Staphylococcus aureus strains compares with that of the glycopeptide antibiotic vancomycin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 521, "text": "Incubation of Staphylococcus simulans 22 with mersacidin resulted in the cessation of growth and slow lysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1437, "text": "n contrast to vancomycin, the activity of mersacidin was not antagonized by the tripeptide diacetyl-L-Lys-D-Ala-D-Ala, indicating that on the molecular level its mode of action differs from those of glycopeptide antibiotics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Inhibition of peptidoglycan biosynthesis by ramoplanin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2334153", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2334153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Bacitracin and other antibiotics that inhibit late stages in peptidoglycan biosynthesis induce vancomycin resistance in a high-level, inducibly vancomycin-resistant strain of Enterococcus faecium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7590155", "endSection": "abstract" }, { "offsetInBeginSection": 1632, "offsetInEndSection": 1814, "text": "This effect does not involve a change in the permeability of the cell wall by this drug and is consistent with the identification of D-alanine racemase as a target of D-cycloserine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11751110", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1459, "text": "CONCLUSIONS: Several pathways and genes downregulated by fosfomycin have been identified, in contrast to previously described cell wall active antibiotics, and was explained by starvation response induced by phosphoenolpyruvate accumulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20515462", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1092, "text": "The target pathway - peptidoglycan biosynthesis - was upregulated following fosfomycin treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20515462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2334153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Fosfomycin inhibited the first enzymatic step of peptidoglycan synthesis, which was followed by decreased levels of peptidoglycan precursors but enhanced levels of substrates such as UDP-GlcNAc and alanine-alanine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25224006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "In contrast, vancomycin and ampicillin inhibited the last stage of peptidoglycan construction on the outer cell surface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25224006", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1197, "text": "The target pathway - peptidoglycan biosynthesis - was upregulated following fosfomycin treatment. Modulation of transport processes, cofactor biosynthesis, energy metabolism and nucleic acid biosynthesis was also observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20515462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2334153", "endSection": "abstract" } ] }, { "body": "Can Levoxyl (levothyroxine sodium) cause insomnia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19701833" ], "ideal_answer": [ "Levoxyl monotherapy is associated with increased insomnia compared to a combination of levothyroxine and liothyronine." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007319" ], "type": "yesno", "id": "52b2ec744003448f55000001", "snippets": [ { "offsetInBeginSection": 200, "offsetInEndSection": 987, "text": "METHODS: Seventy-one patients diagnosed with primary hypothyroidism were randomly allocated into two study groups: the first group received usual dose of levothyroxine and the second group received combination of levothyroxine and liothyronine for at least 4 months. The main outcomes were psychosocial problems (Goldberg's General Health Questionnaire, GHQ-28), bodyweight, heart rate, blood pressure, and serum lipid levels. RESULTS: In both groups serum thyroid-stimulating hormone levels remained unchanged compared with baseline. Psychosocial scores, body weight, heart rate, blood pressure, and lipid profile in the two groups remained constant. The only exception was a small but significant reduction in anxiety/insomnia in combined treatment group as compared with monotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19701833", "endSection": "abstract" } ] }, { "body": "Is fatigue prevalent in patients receiving treatment for glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20510539", "http://www.ncbi.nlm.nih.gov/pubmed/19593660", "http://www.ncbi.nlm.nih.gov/pubmed/3008359", "http://www.ncbi.nlm.nih.gov/pubmed/22832897", "http://www.ncbi.nlm.nih.gov/pubmed/19904263", "http://www.ncbi.nlm.nih.gov/pubmed/2168357", "http://www.ncbi.nlm.nih.gov/pubmed/18758912", "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "http://www.ncbi.nlm.nih.gov/pubmed/23419575", "http://www.ncbi.nlm.nih.gov/pubmed/18477765", "http://www.ncbi.nlm.nih.gov/pubmed/23422478", "http://www.ncbi.nlm.nih.gov/pubmed/14649883", "http://www.ncbi.nlm.nih.gov/pubmed/23642624", "http://www.ncbi.nlm.nih.gov/pubmed/18581057", "http://www.ncbi.nlm.nih.gov/pubmed/18990027", "http://www.ncbi.nlm.nih.gov/pubmed/20308655", "http://www.ncbi.nlm.nih.gov/pubmed/22079725", "http://www.ncbi.nlm.nih.gov/pubmed/21514945", "http://www.ncbi.nlm.nih.gov/pubmed/20200024", "http://www.ncbi.nlm.nih.gov/pubmed/21986722", "http://www.ncbi.nlm.nih.gov/pubmed/22090453", "http://www.ncbi.nlm.nih.gov/pubmed/20665891", "http://www.ncbi.nlm.nih.gov/pubmed/20729242", "http://www.ncbi.nlm.nih.gov/pubmed/23184145" ], "ideal_answer": [ "Yes, fatigue is a common complication of glioblastoma patients receiving chemotherapy or radiotherapy." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3073", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015995", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005909", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005222", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005221" ], "type": "yesno", "id": "530e42e65937551c09000007", "snippets": [ { "offsetInBeginSection": 1468, "offsetInEndSection": 1602, "text": "By contrast, fatigue worsened over time, with a difference in mean score of 5.6 points between baseline and 4-month follow-up (P=.02).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23642624", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 789, "text": "In the GB cohort, the most common side effects were fatigue (56 %), diarrhea (44 %), neutropenia (31 %), and thrombocytopenia (25 %). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22832897", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 969, "text": "A total of 37 patients were treated, and treatment was well tolerated: grade 3, 4 nonhematologic toxicity occurred in 30% of patients and consisted mainly of fatigue (14%) and neuropathy (5%); grade 3, 4 hematologic toxicity occurred in 37% of patients and consisted of thrombocytopenia (30%), lymphopenia (4%), and neutropenia (4%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090453", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1409, "text": "Nonhematologic Grade 3 toxicity was rare, and included fatigue in 4 patients and cognitive disability in 1 patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22079725", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1457, "text": "The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21986722", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 1104, "text": "Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21514945", "endSection": "abstract" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1259, "text": "This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21514945", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1470, "text": "One patient treated with temozolomide plus isotretinoin plus thalidomide had dose-limiting grade 3 fatigue and rash, and 1 patient receiving all 4 agents had dose-limiting grade 4 neutropenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20729242", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 969, "text": "The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20665891", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1779, "text": "Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20510539", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1454, "text": "The most common grades 3 and 4 nonhematologic toxicities were nausea/vomiting (6.7%) and fatigue (5.8%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20308655", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1021, "text": "Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20200024", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 994, "text": "The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19904263", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1205, "text": "Bevacizumab-related toxicity included fatigue (16 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (7; 1 grade 3), deep vein thrombosis (4; 1 grade 3) and wound dehiscence (2; 1 grade 3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19593660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Tiredness may be caused by the brain injury due to the tumor or the treatment in patients with glioblastoma multiforme (GBM). Some patients describe a sense of tiredness particularly after radiation or oral chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18990027", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 996, "text": "Levels of tiredness in patients with GBM were greatly affected by the radiotherapy and oral chemotherapy (temozolomide).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18990027", "endSection": "abstract" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1534, "text": "The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18758912", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1089, "text": " This regimen was well tolerated with grade 3/4 toxicities of fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18581057", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1018, "text": "The most common atrasentan-related toxicities were grade 1 or 2 rhinitis, fatigue, and edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18477765", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 761, "text": "One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14649883", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1378, "text": "Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2168357", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 616, "text": " Some patients suffered from fatigue and weak concentration about three months after the end of radiotherapy, in some cases even the neurologic state was deteriorated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3008359", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1545, "text": "grade 1-2 common toxicities included fever, chills, fatigue, dizziness, nausea, vomiting and headache, neutrophilia and skin painful reactions appeared regularly at levels 3 and 4 (2.5 mg and 3.5 mg). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422478", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1141, "text": "Ten episodes of grade 3/4 adverse events were observed in nine patients, including fatigue (n = 3), thrombocytopenia (n = 4), and myelotoxicity, febrile neutropenia, and pulmonary embolism (each n = 1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419575", "endSection": "abstract" }, { "offsetInBeginSection": 1306, "offsetInEndSection": 1397, "text": "Common adverse events were CTCAE grade 1-2 fatigue, loss of appetite, diarrhea, and nausea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184145", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1097, "text": "The most common grade 3-4 toxicities were venous thrombosis, fatigue, skin reactions, encephalopathy, and neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "endSection": "abstract" } ] }, { "body": "List two common features of Tay syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6538137", "http://www.ncbi.nlm.nih.gov/pubmed/18376101", "http://www.ncbi.nlm.nih.gov/pubmed/9050052", "http://www.ncbi.nlm.nih.gov/pubmed/2087835", "http://www.ncbi.nlm.nih.gov/pubmed/20687499", "http://www.ncbi.nlm.nih.gov/pubmed/10797890", "http://www.ncbi.nlm.nih.gov/pubmed/17504703" ], "ideal_answer": [ "Tay syndrome is a rare autosomal recessive genetic disorder characterized by congenital ichthyosis and trichothiodystrophy (abnormal brittle hair). Other less common features of this syndrome are photosensitivity, low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections." ], "exact_answer": [ [ "ichthyosis" ], [ "trichothiodystrophy" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054463", "http://www.disease-ontology.org/api/metadata/DOID:2960" ], "type": "list", "id": "53358cd2d6d3ac6a3400004e", "snippets": [ { "offsetInBeginSection": 1259, "offsetInEndSection": 1809, "text": "TTD is part of a more broadly defined group of diseases identified as IBIDS (ichthyosis, brittle hair, impaired intelligence, decreased fertility and short stature). Photosensitive cases are also identified as PIBIDS (photosensitivity with IBIDS). Cases without manifest ichthyosis are also identified as PBIDS. These syndromes defy rigorous definition because of clinical variation between patients. The original two cases were described by Tay in oriental siblings, whose parents were first cousins; thus the disease is also known as Tay syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20687499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Tay syndrome or IBIDS is a rare autosomal recessive genetic disorder characterized by congenital ichthyosis and abnormal brittle hair (trichothiodystrophy). Other features include photosensitivity, abnormal nails and multiple developmental defects affecting organs mainly derived from neuroectoderm. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18376101", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 453, "text": "We report a case of trichothiodystrophy initially classified as Tay syndrome that based on clinical features, complementary exams as well as on the disease evolution was labelled as PIBIDS syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17504703", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 401, "text": "Tay-syndrome is a rare monogen-inherited ektodermal dysplastic syndrome with ichtyosis, fragility of the hair and physical and mental retardation. The congenital ichtyosis is ubiquitous. Only the skin on the flexion side of the extremity joints are not involved (orthocerathosis combined with paraceratotic strings).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10797890", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 399, "text": "In Tay syndrome, the trichothiodystrophy is accompanied by congenital ichthyosis, short stature, delayed physical and mental development and pyramidal tract signs with increase in muscular tone and brisk tendon reflexes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9050052", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 775, "text": "We present a case of Tay syndrome in which a cranial MRI revealed an almost total lack of myelin within the cerebral hemispheres and a patchy hypomyelination of the cerebellum. In accordance, a strongly prolonged visual evoked response pointed to a dysfunction of the white matter in Tay syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9050052", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 458, "text": "For example, the brittle hair due to sulphur deficiency (trichothiodystrophy) is nowadays regarded as genetically heterogeneous; three different syndromes can be distinguished: BIDS syndrome, Tay syndrome, and PIBIDS syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2087835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "The Tay syndrome (congenital ichthyosis with trichothiodystrophy).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6538137", "endSection": "title" }, { "offsetInBeginSection": 147, "offsetInEndSection": 302, "text": "The Tay syndrome is a distinct type of congenital ichthyosis characterized by a peculiar anomaly of hair growth which has been termed trichothiodystrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6538137", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 789, "text": "Other features of this syndrome are low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6538137", "endSection": "abstract" } ] }, { "body": "Which cell types are known to be driving Rheumatoid Arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19863844", "http://www.ncbi.nlm.nih.gov/pubmed/15692990", "http://www.ncbi.nlm.nih.gov/pubmed/21160042", "http://www.ncbi.nlm.nih.gov/pubmed/24276088", "http://www.ncbi.nlm.nih.gov/pubmed/18613841", "http://www.ncbi.nlm.nih.gov/pubmed/16567358", "http://www.ncbi.nlm.nih.gov/pubmed/17875202", "http://www.ncbi.nlm.nih.gov/pubmed/12060849", "http://www.ncbi.nlm.nih.gov/pubmed/15641091", "http://www.ncbi.nlm.nih.gov/pubmed/23036591", "http://www.ncbi.nlm.nih.gov/pubmed/20519953" ], "ideal_answer": [ "Macrophages, T cells and their respective cytokines play a pivotal role in RA. Rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. Activated synovial fibroblasts (SFs) have the ability to invade joint cartilage, actively contributing to joint destruction in RA." ], "exact_answer": [ [ "Macrophages" ], [ "T-cells" ], [ "Fibroblast-like synoviocytes (FLS)" ], [ "Dendritic cells" ], [ "synovial fibroblasts" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005623" ], "type": "list", "id": "52b2d405f828ad283c000009", "snippets": [ { "offsetInBeginSection": 471, "offsetInEndSection": 646, "text": "Integration of GWAS results with cell-type specific gene expression or epigenetic marks have highlighted regulatory T cells and CD4 memory T cells as critical cell types in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276088", "endSection": "abstract" }, { "offsetInBeginSection": 2100, "offsetInEndSection": 2172, "text": "A subset of synovial DCs is important in the response to cigarette smoke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036591", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1159, "text": " we demonstrate that autoimmune patient (systemic lupus erythematosus and rheumatoid arthritis) serum activates both pDC and B cells, but IRAK1/4 kinase inhibition affects only the pDC response, underscoring the differential IRAK1/4 functional requirements in human immune cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21160042", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 588, "text": "In rheumatoid arthritis (RA), activated synovial fibroblasts (SFs) have the ability to invade joint cartilage, actively contributing to joint destruction in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20519953", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 733, "text": "Recently, RASFs have been shown to be able to migrate to non-affected areas and joints through the blood stream and to invade distant cartilage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20519953", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1530, "text": "MSC interaction with B cells provides stimuli for B-cell survival and therefore may contribute to the pathogenesis of rheumatoid arthritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863844", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 211, "text": "Fibroblast-like synoviocytes (FLS) are resident mesenchymal cells of synovial joints that have been recognized to play an increasingly important role in the pathogenesis of rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18613841", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 434, "text": "This study investigates the production of CCL18 in polymorphonuclear neutrophils (PMN), the predominant cell type recruited into synovial fluid (SF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17875202", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 333, "text": "In this regard, macrophages, T cells and their respective cytokines play a pivotal role in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16567358", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 630, "text": "it has been understood that resident, fibroblast-like cells contribute significantly to the perpetuation of disease, and that they may even play a role in its initiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16567358", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1299, "text": "RASFs are no longer considered passive bystanders but active players in the complex intercellular network of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16567358", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 794, "text": "These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16567358", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1692, "text": "The molecular feature that defines the myofibroblast-like phenotype was reflected as an increased proportion of myofibroblast-like cells in the heterogeneous FLS population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15692990", "endSection": "abstract" }, { "offsetInBeginSection": 1803, "offsetInEndSection": 2027, "text": "ur findings support the notion that heterogeneity between synovial tissues is reflected in FLS as a stable trait, and provide evidence of a possible link between the behavior of FLS and the inflammation status of RA synovium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15692990", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1072, "text": "This change was accompanied by a significant decrease in the synovial monocyte/macrophage population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15641091", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1611, "text": "In RA patients, both etanercept and infliximab are able to induce cell type-specific apoptosis in the monocyte/macrophage population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15641091", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 956, "text": "Furthermore, fluorescent double-staining showed that the HOXD9 protein was expressed in fibroblast-like synoviocytes (FLS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12060849", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1251, "text": "AHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036591", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 707, "text": "Twenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036591", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 284, "text": "Release of the chemokine CCL18 has been widely attributed to antigen-presenting cells, including macrophages and dendritic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17875202", "endSection": "abstract" } ] }, { "body": "What is the association between personality trait of neuroticism and risk for Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23040035", "http://www.ncbi.nlm.nih.gov/pubmed/19153372", "http://www.ncbi.nlm.nih.gov/pubmed/20973606", "http://www.ncbi.nlm.nih.gov/pubmed/17244848", "http://www.ncbi.nlm.nih.gov/pubmed/18590355", "http://www.ncbi.nlm.nih.gov/pubmed/20438208", "http://www.ncbi.nlm.nih.gov/pubmed/16252381", "http://www.ncbi.nlm.nih.gov/pubmed/7493597", "http://www.ncbi.nlm.nih.gov/pubmed/10718200", "http://www.ncbi.nlm.nih.gov/pubmed/16314587", "http://www.ncbi.nlm.nih.gov/pubmed/16974109", "http://www.ncbi.nlm.nih.gov/pubmed/21835104", "http://www.ncbi.nlm.nih.gov/pubmed/23706517", "http://www.ncbi.nlm.nih.gov/pubmed/23567438", "http://www.ncbi.nlm.nih.gov/pubmed/22040898", "http://www.ncbi.nlm.nih.gov/pubmed/18079420", "http://www.ncbi.nlm.nih.gov/pubmed/10679843", "http://www.ncbi.nlm.nih.gov/pubmed/12767492", "http://www.ncbi.nlm.nih.gov/pubmed/15358438", "http://www.ncbi.nlm.nih.gov/pubmed/23079898", "http://www.ncbi.nlm.nih.gov/pubmed/21905097", "http://www.ncbi.nlm.nih.gov/pubmed/18694539", "http://www.ncbi.nlm.nih.gov/pubmed/21427641", "http://www.ncbi.nlm.nih.gov/pubmed/25274849", "http://www.ncbi.nlm.nih.gov/pubmed/9924832" ], "ideal_answer": [ "High neuroticism is associated with increased risk to develop Alzheimer's disease. Greater neuroticism is also associated more advanced Alzheimer's disease neuropathology and younger age of dementia onset. Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety. Neuroticism moderates the relationship between APOE-4 genotype and cognitive outcomes in elderly. Neuroticism also predicts Mild Cognitive Impairment, Aging-Associated Cognitive Decline and cognitive decline among elderly. Alzheimer's disease patients have greater neuroticism relative to controls." ], "type": "summary", "id": "550324d7e9bde6963400002f", "snippets": [ { "offsetInBeginSection": 415, "offsetInEndSection": 685, "text": "RESULTS: Individuals with scores in the top quartile of neuroticism (hazard ratio = 3.1; 95% confidence interval = 1.6-6.0) or the lowest quartile of conscientiousness (hazard ratio = 3.3; 95% confidence interval = 1.4-7.4) had a threefold increased risk of incident AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23706517", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 967, "text": "Five of nine studies found that higher neuroticism was associated with greater dementia risk (pooled hazard ratio [HR] per unit increase on neuroticism score, HR\u00a0= 1.13, 95% confidence interval [CI]\u00a0= 1.08-1.18, z\u00a0= 5.11, p\u00a0<0.001, N\u00a0= 3,285), and two studies showed it increased risk of MCI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567438", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1609, "text": "CONCLUSIONS: Neuroticism increased risk for dementia, and conscientiousness reduced risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567438", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 1194, "text": "RESULTS: Fully adjusted multivariate analyses showed that the association between the presence of APOE [Latin Small Letter Open E]-4 allele(s) and both outcomes was evident among individuals with high levels of neuroticism and extraversion but not among persons with low levels of these traits. CONCLUSIONS: Phenotypic personality dimensions, primarily neuroticism and extraversion, moderate the relationship between APOE [Latin Small Letter Open E]-4 genotype and cognitive outcomes among older adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23079898", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 1181, "text": " Individuals with higher baseline scores on vulnerability to stress, anxiety, and depression (neuroticism: odds ratio, 2.0; 95% confidence interval, 1.2-3.5), or lower scores on order and competence (conscientiousness: odds ratio, 0.4; 95% confidence interval, 0.2-0.9) were less likely to remain asymptomatic in the presence of AD neuropathology. Neuroticism (r = 0.26), low agreeableness (r = -0.34), and some facets were also significantly associated with advanced stages of neurofibrillary tangles, but the associations between personality traits and risk of clinical dementia were mostly unchanged by controlling for the extent of neurofibrillary tangles and A\u03b2 neuritic plaques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040035", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 518, "text": "Using mixed models adjusted for age, sex, education, race, social network size, depression, chronic conditions, disability, neuroticism, extraversion, cognitive activity, and physical activity, more social activity was associated with less cognitive decline during average follow-up of 5.2 years (SD = 2.7).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22040898", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 1007, "text": "RESULTS: After controlling for age, the Alzheimer disease group presented significantly higher scores than normal control subjects on current neuroticism, and significantly lower scores on current extraversion, openness, and conscientiousness, while no significant difference was observed on agreeableness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835104", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1458, "text": " In analyses of specific cognitive systems, neuroticism subscales were related to decline in episodic memory, working memory, and perceptual speed, but not in semantic memory or visuospatial ability. No component of neuroticism was related to the neuropathologic lesions most commonly associated with late-life dementia. CONCLUSIONS: Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety and their correlation with decline in the ability to process and retain new information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21427641", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 993, "text": "The finding that AD risk is associated with elevated Neuroticism and lower Conscientiousness can be added to the accumulating literature documenting the pathogenic effects of these two traits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20973606", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1315, "text": "tau was also correlated with the psychometric measures of episodic/semantic memory, working memory, and processing speed, and with the personality traits of neuroticism and conscientiousness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20438208", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 300, "text": "The pre-morbid personality domain of Neuroticism constituted an interesting and theoretically plausible, yet uninvestigated, candidate for such an association. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18694539", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1042, "text": "RESULTS: Midlife Neuroticism predicted younger age of dementia onset in females but not in males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18694539", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 497, "text": "Preliminary research suggests that cognitively impaired MS patients exhibit elevation in Neuroticism, and diminution in Extraversion, Agreeableness, and Conscientiousness, as do patients with Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18590355", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 694, "text": "On the basis of both self-report and informant report, there was an increase in neuroticism and a decrease in conscientiousness in persons with very mild DAT relative to healthy individuals without it, and in persons with mild DAT relative to those with very mild DAT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18079420", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1481, "text": "CONCLUSIONS: As subjective cognitive complaints in the AACD group were related to neuroticism and gender rather than to cognitive performance, their inclusion in diagnostic concepts such as AACD should be revaluated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16252381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Multiple studies of individuals with Alzheimer disease have substantiated significant levels of informant-rated change in several domains and facets of the Neuroticism-Extraversion-Openness Personality Inventory, including increases in Neuroticism and decreases in Extraversion and Conscientiousness relative to premorbid personality traits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10718200", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 556, "text": "RESULTS: The AD patients showed higher neuroticism than the controls with PD (p=0.013). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10679843", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 880, "text": "CONCLUSION: Our results support the assumption of specific premorbid characteristics in AD patients, ie increased neuroticism and rigidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10679843", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 535, "text": "Personality change in DAT was consistent with previous reports of increased neuroticism, decreased extraversion, and decreased conscientiousness, with smaller decreases in openness and agreeableness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7493597", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1180, "text": "Neuroticism (r = 0.26), low agreeableness (r = -0.34), and some facets were also significantly associated with advanced stages of neurofibrillary tangles, but the associations between personality traits and risk of clinical dementia were mostly unchanged by controlling for the extent of neurofibrillary tangles and A\ufffd neuritic plaques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Multiple studies of individuals with Alzheimer disease have substantiated significant levels of informant-rated change in several domains and facets of the Neuroticism-Extraversion-Openness Personality Inventory, including increases in Neuroticism and decreases in Extraversion and Conscientiousness relative to premorbid personality traits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10718200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Multiple studies of individuals with Alzheimer disease have substantiated significant levels of informant-rated change in several domains and facets of the Neuroticism-Extraversion-Openness Personality Inventory, including increases in Neuroticism and decreases in Extraversion and Conscientiousness relative to premorbid personality traits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10718200", "endSection": "abstract" } ] }, { "body": "What is the mode of action of everolimus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17890266", "http://www.ncbi.nlm.nih.gov/pubmed/24183081", "http://www.ncbi.nlm.nih.gov/pubmed/19620795", "http://www.ncbi.nlm.nih.gov/pubmed/20384580", "http://www.ncbi.nlm.nih.gov/pubmed/19299048", "http://www.ncbi.nlm.nih.gov/pubmed/16625599", "http://www.ncbi.nlm.nih.gov/pubmed/16699448", "http://www.ncbi.nlm.nih.gov/pubmed/21279702", "http://www.ncbi.nlm.nih.gov/pubmed/18025810", "http://www.ncbi.nlm.nih.gov/pubmed/22139982" ], "ideal_answer": [ "Everolimus is a drug that binds to mTORC1 and inhibits activation of the mTOR signalling pathway. It is used in targeted cancer therapy protocols or after transplantation for maintenance immunosuppression, against allograft rejection." ], "concepts": [ "http://www.biosemantics.org/jochem#4267185" ], "type": "summary", "id": "52f125332059c6d71c000007", "snippets": [ { "offsetInBeginSection": 520, "offsetInEndSection": 575, "text": "Target-of-Rapamycin Inhibitors (Sirolimus, Everolimus),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22139982", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 372, "text": "Although the mTOR inhibitor everolimus is effective for the treatment of patients who have failed TKI therapy, it is important to consider all available treatment options before switching therapy mode of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279702", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 771, "text": "The mTOR pathway, and its upstream regulators in the PI3K/PTEN/AKT cascade, are altered in a variety of experimental and human malignancies.This has led to the prediction that mTOR inhibitors may be used as anticancer agents. With the recent approval of two mTOR-targeted drugs (temsirolimus and everolimus) for the treatment of renal cell carcinoma and mantle cell lymphoma, this paradigm has been effectively translated into the clinical setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20384580", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 811, "text": "mTOR inhibitors such as Temsirolimus (CCI779) and Everolimus (RAD001) are effective for suppressing cell growth with inhibiting mTOR kinase activity. Rapamycin and its related analogs such as Temsirolimus and Everolimus are less toxic for humans compared with other anti-VEGFR inhibitors and has been used as an immunosuppressive agent. These agents have an inhibitory activity against the mTORC1 complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19620795", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 887, "text": "mTOR inhibitors act on the signaling pathway PI3K/AKT/mTOR, and key molecules are temsirolimus, everolimus, and deforolimus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19299048", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 690, "text": "The introduction of the inhibitors of the mammalian target of rapamycin sirolimus and everolimus in renal transplantation has increased the repertoire of immunosuppressive protocols substantially.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17890266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Octreotide and the mTOR inhibitor RAD001 (everolimus) block proliferation and interact with the Akt-mTOR-p70S6K pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025810", "endSection": "title" }, { "offsetInBeginSection": 368, "offsetInEndSection": 508, "text": "RAD001 (everolimus) is a novel agent that is being trialled in the treatment of neuro-endocrine tumours, and is known to interact with mTOR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025810", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1305, "text": "In this cell model, octreotide and RAD001 appear to act through a similar pathway and inhibit the Akt-mTOR-p70S6 kinase pathway downstream of Akt.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Target of rapamycin inhibitors (sirolimus and everolimus)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16699448", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16625599", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 131, "text": "Target of rapamycin inhibitors (TOR-I) (sirolimus, everolimus) are immunosuppressive agents with a novel mode of action", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16625599", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 625, "text": "These three classes are tyrosine kinase inhibitors with sunitinib and sorafenib, the anti-VEGF antibodies (bevacizumab which is associated with alpha interferon in the treatment of advanced kidney cancer) and mTOR inhibitors with temsirolimus and everolimus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183081", "endSection": "abstract" } ] }, { "body": "Have Quantitative Trait Loci affecting splicing (splicing QTLs) been linked to disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21846806", "http://www.ncbi.nlm.nih.gov/pubmed/20707912", "http://www.ncbi.nlm.nih.gov/pubmed/22784570", "http://www.ncbi.nlm.nih.gov/pubmed/20856809" ], "ideal_answer": [ "Yes, mutations in the DNA that affect the splicing pattern of genes have been linked in transcriptome population studies to a number of diseases." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056426", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000395", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000381", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040641", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022821", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000398", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043484", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019655", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045291", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008380", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006376" ], "type": "yesno", "id": "5158a5b8d24251bc05000097", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 616, "text": "The spontaneously hypertensive rat (SHR) is a widely used rodent model of hypertension and metabolic syndrome. Previously we identified thousands of cis-regulated expression quantitative trait loci (eQTLs) across multiple tissues using a panel of rat recombinant inbred (RI) strains derived from Brown Norway and SHR progenitors. These cis-eQTLs represent potential susceptibility loci underlying physiological and pathophysiological traits manifested in SHR. We have prioritized 60 cis-eQTLs and confirmed differential expression between the parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21846806", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1713, "text": "These colocalizing correlated cis-eQTLs (c3-eQTLs) are highly attractive as primary susceptibility loci for the colocalizing pQTLs. Furthermore, sequence analysis of the c3-eQTL genes identified single nucleotide polymorphisms (SNPs) that are predicted to affect transcription factor binding affinity, splicing and protein function. These SNPs, which potentially alter transcript abundance and stability, represent strong candidate factors underlying not just eQTL expression phenotypes, but also the correlated metabolic and physiological traits. In conclusion, by integration of genomic sequence, eQTL and QTT datasets we have identified several genes that are strong positional candidates for pathophysiological traits observed in the SHR strain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21846806", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1107, "text": "Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application.RESULTS: Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants.CONCLUSION: Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20707912", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1851, "text": "The six genes corresponded to rat and mouse quantitative trait loci (QTLs) that had shown associations with the common traits such as the well characterized MS and even tumor susceptibility. Our findings suggest that the six genes may play important roles in the pleiotropic effects on lipid metabolism and the MS, which increase the risk of Type 2 Diabetes and cardiovascular disease. The use of the multivariate phenotypes can be advantageous in identifying genetic risk factors, accounting for the pleiotropic effects when the multivariate phenotypes have a common etiological pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22784570", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 693, "text": "To elucidate mechanisms involved in multiple sclerosis (MS), we studied genetic regulation of experimental autoimmune encephalomyelitis (EAE) in rats, assuming a conservation of pathogenic pathways. In this study, we focused on Eae23, originally identified to regulate EAE in a (LEW.1AV1xPVG.1AV1)F2 cross. Our aim was to determine whether one or more genes within the 67 Mb region regulate EAE and to define candidate risk genes.METHODOLOGY/PRINCIPAL FINDINGS: We used high resolution quantitative trait loci (QTL) analysis in the 10th generation (G10) of an advanced intercross line (AIL) to resolve Eae23 into two QTLs that independently regulate EAE, namely Eae23a and Eae23b. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20856809", "endSection": "abstract" } ] }, { "body": "Which technique is used for detection of EWS/FLI1 fusion transcripts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23475435", "http://www.ncbi.nlm.nih.gov/pubmed/20231617", "http://www.ncbi.nlm.nih.gov/pubmed/9552022", "http://www.ncbi.nlm.nih.gov/pubmed/16157025", "http://www.ncbi.nlm.nih.gov/pubmed/9135495", "http://www.ncbi.nlm.nih.gov/pubmed/24293381", "http://www.ncbi.nlm.nih.gov/pubmed/10379685", "http://www.ncbi.nlm.nih.gov/pubmed/17154184", "http://www.ncbi.nlm.nih.gov/pubmed/15363317", "http://www.ncbi.nlm.nih.gov/pubmed/15565546" ], "ideal_answer": [ "Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors is carried out by reverse transcription-polymerase chain reaction (RT-PCR)." ], "exact_answer": [ "Reverse transcription - polymerase chain reaction (RT-PCR)" ], "type": "factoid", "id": "553653a5bc4f83e828000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 520, "text": "We evaluated the feasibility and usefulness of reverse transcriptase-polymerase chain reaction (RT-PCR) on fine-needle aspirates for categorization of small blue round cell tumors (SBRCTs). A total of 51 cases, including 25 Ewing sarcoma/peripheral primitive neuroectodermal tumors (PNETs), 11 rhabdomyosarcomas, 13 neuroblastomas, and 2 desmoplastic small round cell tumors (DSRCTs) were analyzed. The detection of the EWS-FLI1 (20/25) and EWS-ERG (4/25) fusion transcripts resolved 24 of 25 cases of Ewing sarcoma/PNET", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20231617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10379685", "endSection": "title" }, { "offsetInBeginSection": 374, "offsetInEndSection": 1042, "text": "To assess the feasibility and reliability of the molecular detection of the transcript originating from the chimeric gene in paraffin-embedded tumor specimens, we performed a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the EWS-FLI1 chimeric message in a series of Ewing family tumors. Of 24 paraffin-embedded tumor specimens from 23 cases analyzed, the chimeric message was detectable in 20 (83%) specimens from 20 cases (87%) by this nested RT-PCR assay, whereas none of 7 small round cell tumors not from this family (3 alveolar rhabdomyosarcomas, 2 neuroblastomas, 2 malignant lymphomas) showed detectable chimeric messages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10379685", "endSection": "abstract" }, { "offsetInBeginSection": 3113, "offsetInEndSection": 3359, "text": "Using our different sets of exon specific primer pairs, it was possible to detect 4 different breakpoints of ews/fli1 fusion transcripts and the ews/erg fusion by RT-PCR in RNA isolates from formalin-fixed, paraffin-embedded Ewing's tumor tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565546", "endSection": "abstract" }, { "offsetInBeginSection": 1814, "offsetInEndSection": 2011, "text": "Molecular detection of EWS-Fli1 fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16157025", "endSection": "abstract" }, { "offsetInBeginSection": 1729, "offsetInEndSection": 2045, "text": "We established a novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs, selected according to the coding ews and fli1 nucleotide sequences (NCBI database), suitable for RT-PCR identification of variant ews/fli1 fusion transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565546", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 393, "text": "In this study, we evaluated reverse transcriptase-polymerase chain (RT-PCR) for EWS-FLI1 fusion transcripts in 18 neurally derived small round cell tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9135495", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 869, "text": "We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9552022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Molecular detection of EWS-Fli1 fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16157025", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 677, "text": "RT-PCR confirmed that SK-NEP-1 expresses EWS-FLI1 gene fusion transcripts characteristic of Ewing sarcoma, and DNA sequencing demonstrated the joining of exon 7 of EWS with exon 5 of FLI1 for these transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17154184", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 937, "text": "Reverse transcriptase-polymerase chain reaction confirmed the expression of EWS-FLI1 fusion transcripts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475435", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 626, "text": "The aims of this study were (1) to present the diverse clinicopathological and molecular profile of EFTs in our settings, (2) to identify a pragmatic approach for diagnosing EFTs, especially for application of ancillary techniques, namely RT-PCR for specific transcripts (EWS-FLI1, EWS-ERG) and FISH for EWSR1 gene rearrangement, in certain cases and (3) to show the utility of tissue microarray in establishing a new FISH test", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "[Detection of EWS-FLI1 fusion transcript in Ewing's sarcoma/peripheral primitive neuroectodermal tumors by one-step RT-PCR using paraffin-embedded tissues].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15363317", "endSection": "title" }, { "offsetInBeginSection": 1835, "offsetInEndSection": 2032, "text": "Molecular detection of EWS-Fli1 fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16157025", "endSection": "abstract" }, { "offsetInBeginSection": 1751, "offsetInEndSection": 2066, "text": "We established a novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs, selected according to the coding ews and fli1 nucleotide sequences (NCBI database), suitable for RT-PCR identification of variant ews/fli1 fusion transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction: application to archival paraffin-embedded tumor tissues.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10379685", "endSection": "title" } ] }, { "body": "Does the CTCF protein co-localize with cohesin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "http://www.ncbi.nlm.nih.gov/pubmed/23010778", "http://www.ncbi.nlm.nih.gov/pubmed/19158269", "http://www.ncbi.nlm.nih.gov/pubmed/22550178", "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "http://www.ncbi.nlm.nih.gov/pubmed/23204437", "http://www.ncbi.nlm.nih.gov/pubmed/18623068", "http://www.ncbi.nlm.nih.gov/pubmed/21876668", "http://www.ncbi.nlm.nih.gov/pubmed/19308701", "http://www.ncbi.nlm.nih.gov/pubmed/21444719", "http://www.ncbi.nlm.nih.gov/pubmed/24257606", "http://www.ncbi.nlm.nih.gov/pubmed/20133600", "http://www.ncbi.nlm.nih.gov/pubmed/21880767", "http://www.ncbi.nlm.nih.gov/pubmed/21106760", "http://www.ncbi.nlm.nih.gov/pubmed/23945083", "http://www.ncbi.nlm.nih.gov/pubmed/22952237", "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "http://www.ncbi.nlm.nih.gov/pubmed/18550811", "http://www.ncbi.nlm.nih.gov/pubmed/21948239", "http://www.ncbi.nlm.nih.gov/pubmed/21970734", "http://www.ncbi.nlm.nih.gov/pubmed/22440186", "http://www.ncbi.nlm.nih.gov/pubmed/24321385", "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "http://www.ncbi.nlm.nih.gov/pubmed/23295672", "http://www.ncbi.nlm.nih.gov/pubmed/21606361", "http://www.ncbi.nlm.nih.gov/pubmed/23804403", "http://www.ncbi.nlm.nih.gov/pubmed/23498937" ], "ideal_answer": [ "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin.", "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin " ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/CTCF_RAT", "http://www.uniprot.org/uniprot/CTCFL_HUMAN" ], "type": "yesno", "id": "5344310baeec6fbd0700000c", "snippets": [ { "offsetInBeginSection": 348, "offsetInEndSection": 560, "text": "To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 886, "text": "In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 541, "text": "Here we report that cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 834, "text": "By use of human hepatocellular carcinoma cells (HepG2), we found that liver-specific transcription factors colocalize with cohesin independently of CTCF at liver-specific targets that are distinct from those found in breast cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 879, "text": "Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 486, "text": "Here we show that zebrafish runx1 is directly bound by cohesin and CCCTC binding factor (CTCF) at the P1 and P2 promoters, and within the intron between P1 and P2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321385", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 866, "text": "The intronic binding sites for cohesin and CTCF coincide with histone modifications that confer enhancer-like properties, and two of the cohesin/CTCF sites behaved as insulators in an in vivo assay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321385", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1023, "text": "The identified cohesin and CTCF binding sites are likely to be cis-regulatory elements (CREs) for runx1 since they also recruit RNA polymerase II (RNAPII).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321385", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 387, "text": "We have found that CTCF and cohesin are highly enriched at the convergent and partially overlapping transcripts for the LMP1 and LMP2A genes, but it is not yet known how CTCF and cohesin may coordinately regulate these transcripts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257606", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 124, "text": "haracterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945083", "endSection": "title" }, { "offsetInBeginSection": 744, "offsetInEndSection": 890, "text": "Our analysis revealed: 1) constitutive CTCF loci were located in constitutive open chromatin and often co-localized with constitutive cohesin loci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945083", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 922, "text": "In brain, a third of CTCF and cohesin binding sites coincide, consistent with the potential for many interactions between cohesin and CTCF but also many instances of independent action", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23804403", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 389, "text": "Here, we focus on the emerging roles of CTCF and the cohesin in coordinating long-range interactions between regulatory elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23498937", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 1018, "text": "Chromatin immunoprecipitation for CTCF and the cohesin subunits RAD21 and SMC3 reveals evolutionarily conserved binding sites within unmethylated regions \u223c5 kb downstream of the PLAGL1 differentially methylated region and within the PLAGL1 3' untranslated region (UTR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23295672", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 42, "text": "TCF physically links cohesin to chromatin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18550811", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 65, "text": "ohesin and CTCF: cooperating to control chromosome conformation?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18623068", "endSection": "title" }, { "offsetInBeginSection": 222, "offsetInEndSection": 374, "text": "Recently, three groups mapped numerous cohesin-binding sites in mammalian chromosomes and found substantial overlap with the CCCTC-binding factor (CTCF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18623068", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 644, "text": "We found that each site contains a conserved CTCF consensus sequence, binds CTCF, and recruits the cohesin subunit Rad21 in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19158269", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 408, "text": "Recent experiments have revealed that cohesin binds to the same sites in mammalian genomes as the zinc finger transcription factor CTCF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19308701", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 765, "text": "Here we review what is known about the roles of cohesin and CTCF in regulating gene expression in mammalian cells, and we discuss how cohesin might mediate the insulator function of CTCF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19308701", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 674, "text": "Previous studies have shown that this major latency control region is occupied by the cellular chromatin boundary factor CTCF and chromosome structural maintenance proteins SMC1, SMC3, and RAD21, which comprise the cohesin complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1070, "text": "Cohesin subunits assembled at the CTCF binding sites and bound CTCF proteins in a cell cycle-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "endSection": "abstract" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1788, "text": "We propose that the CTCF-cohesin complex plays a critical role in regulating the cell cycle control of viral gene expression during latency and that failure to maintain cell cycle control of latent transcripts inhibits host cell proliferation and survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 298, "text": "We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the beta-globin locus and flanking olfactory receptor genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20133600", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1115, "text": "These results support a genome-wide role for CTCF/cohesin sites through loop formation that both influences transcription and contributes to cell-type-specific chromatin organization and function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20133600", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 892, "text": "Increased methylation at this promoter triggered the dissociation of the insulator protein CTCF as well as the accompanying cohesin from the BDNF locus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106760", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 152, "text": "icotinamide adenine dinucleotide (NAD)-regulated DNA methylation alters CCCTC-binding factor (CTCF)/cohesin binding and transcription at the BDNF locus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106760", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 234, "text": "ecent studies have shown that the protein CTCF, which plays an important role in insulation and in large-scale organization of chromatin within the eukaryotic nucleus, depends for both activities on recruitment of the cohesin complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21444719", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 411, "text": "We show here that the interaction of CTCF with the cohesin complex involves direct contacts between the cohesin subunit SA2 and specific regions of the C-terminal tail of CTCF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21444719", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 885, "text": "Taken together, our results demonstrate that specific sites on the C terminus of CTCF are essential for cohesin binding and insulator function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21444719", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1004, "text": "The only direct interaction between CTCF and cohesin involves contact with SA2, which is external to the cohesin ring", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21444719", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 788, "text": "These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606361", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 399, "text": "We have previously shown that the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) major latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are regulated, in part, by a chromatin organizing element that binds CTCF and cohesins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876668", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 924, "text": "Mutation of the CTCF-cohesin binding site reduced or eliminated the chromatin conformation linkages, and deregulated viral transcription and genome copy number control", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876668", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1483, "text": "Our findings indicate that KSHV genomes are organized into chromatin loops mediated by CTCF and cohesin interactions, and that these inter-chromosomal linkages coordinate latent and lytic gene control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876668", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 491, "text": "We show here that GA disrupts an RNA polymerase II (RNAPII) complex that accumulates at the CTCF-cohesin binding site within the first intron of the latency transcript.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880767", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 638, "text": "GA altered the enrichment of the RNAPII pausing complex, along with pausing factors SPT5 and NELF-A, at the intragenic CTCF-cohesin binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880767", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1116, "text": "GA treatment also inhibited the transcription of some cellular genes, like c-myc, which contain a similar CTCF-cohesin binding site within the first intron.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880767", "endSection": "abstract" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1499, "text": "These findings suggest that RNAPII pauses at intragenic CTCF-cohesin binding sites and that abrogation of this pausing by GA leads to loss of proper mRNA production and defects in sister chromatid cohesion, a process important for both viral and cellular chromosome stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880767", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 120, "text": "TCF and cohesin cooperatively mediate the cell-type specific interchromatin interaction between Bcl11b and Arhgap6 loci", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21948239", "endSection": "title" }, { "offsetInBeginSection": 467, "offsetInEndSection": 648, "text": "Additional experiments verified that the interchromatin interaction between the Bcl11b and Arhgap6 loci was cell-type specific, which was cooperatively mediated by CTCF and cohesin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21948239", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 118, "text": "enome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight into chromatin structure and regulation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952237", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 544, "text": "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952237", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 375, "text": "Here, we show by ChIP-Seq that most human subtelomeres contain a CTCF- and cohesin-binding site within \u223c1-2\u2009kb of the TTAGGG repeat tract and adjacent to a CpG-islands implicated in TERRA transcription control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23010778", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1155, "text": "These findings indicate that CTCF and cohesin are integral components of most human subtelomeres, and important for the regulation of TERRA transcription and telomere end protection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23010778", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 731, "text": "In addition, we show that this DNA looping requires specific binding of the CTCF/cohesin complex to two symmetrically aligned binding sites in both the transcriptionally active promoters and in one of the enhancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204437", "endSection": "abstract" } ] }, { "body": "What is the application of the Bimolecular Fluorescence Complementation (BiFC) assay in Drosophila embryos?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16454041", "http://www.ncbi.nlm.nih.gov/pubmed/18155474", "http://www.ncbi.nlm.nih.gov/pubmed/19771334", "http://www.ncbi.nlm.nih.gov/pubmed/18573091", "http://www.ncbi.nlm.nih.gov/pubmed/17406412", "http://www.ncbi.nlm.nih.gov/pubmed/25151172", "http://www.ncbi.nlm.nih.gov/pubmed/23317900", "http://www.ncbi.nlm.nih.gov/pubmed/21091444", "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "http://www.ncbi.nlm.nih.gov/pubmed/17534848" ], "ideal_answer": [ "Bimolecular fluorescence complementation (BiFC) is a powerful method for studying protein-protein interactions in different cell types and organisms. This method was recently developed in the fruit fly Drosophila melanogaster, allowing analyzing protein interaction properties in a physiologically relevant developing context." ], "exact_answer": [ "The study of protein-protein interactions in a physiologically relevant developing context." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004331", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005453", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013050" ], "type": "factoid", "id": "56c868a95795f9a73e000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 598, "text": "Bimolecular fluorescence complementation (BiFC) is a powerful method for studying protein-protein interactions in different cell types and organisms. This method was recently developed in the fruit fly Drosophila melanogaster, allowing analyzing protein interaction properties in a physiologically relevant developing context. Here we present a detailed protocol for performing BiFC with the Venus fluorescent protein in live Drosophila embryos, taking the Hox-PBC partnership as an illustrative test case. This protocol applies to any transcription factor and split fluorescent protein in general.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25151172", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 416, "text": "The understanding of developmental complexity will, therefore, require the characterization of protein interactions within their proper environment. The bimolecular fluorescence complementation (BiFC) technology offers this possibility as it enables the direct visualization of protein interactions in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 1119, "text": "Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. Importantly, all BiFC parameters were established with constructs that were stably expressed under the control of endogenous promoters. Under these physiological conditions, we showed that BiFC is specific and sensitive enough to analyse dynamic protein interactions. We next used BiFC in a candidate interaction screen, which led to the identification of several Hox protein partners.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 657, "text": "Using fluorescent proteins, we previously developed a bimolecular fluorescence complementation (BiFC) assay and a multicolor BiFC assay to visualize protein-protein interactions in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16454041", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 562, "text": "The bimolecular fluorescence complementation (BiFC) assay represents one of these imaging tools for direct visualization of PPIs in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21091444", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 455, "text": "The bimolecular fluorescence complementation (BiFC) assay provides an approach for the visualization of protein interactions and modifications in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19771334", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 580, "text": "The bimolecular fluorescence complementation (BiFC) assay provides a direct approach for the visualization of molecular interactions in living cells and organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18155474", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 949, "text": "The purpose of this protocol is to calculate signal-to-noise (S/N) ratio in the bimolecular fluorescence complementation (BiFC) assay and to provide a semi-quantitative analysis of protein-protein interaction (PPI) in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23317900", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 605, "text": "Bimolecular fluorescence complementation (BiFC) analysis enables direct visualization of protein interactions in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18573091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The bimolecular fluorescence complementation (BiFC) assay has been widely accepted for studying in vivo detection of protein-protein interactions in several organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17534848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Visualization of protein interactions in living Drosophila embryos by the bimolecular fluorescence complementation assay.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "title" }, { "offsetInBeginSection": 567, "offsetInEndSection": 735, "text": "RESULTS: Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17406412", "endSection": "title" }, { "offsetInBeginSection": 417, "offsetInEndSection": 735, "text": "However, its potential has rarely been applied in embryos of animal model organisms and was only performed under transient protein expression levels. RESULTS: Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 715, "text": "However, its potential has rarely been applied in embryos of animal model organisms and was only performed under transient protein expression levels. Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 555, "text": "The bimolecular fluorescence complementation (BiFC) technology offers this possibility as it enables the direct visualization of protein interactions in living cells. However, its potential has rarely been applied in embryos of animal model organisms and was only performed under transient protein expression levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 466, "text": "we previously developed a bimolecular fluorescence complementation (BiFC) assay and a multicolor BiFC assay to visualize protein-protein interactions in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16454041", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 715, "text": "Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 466, "text": "Using fluorescent proteins, we previously developed a bimolecular fluorescence complementation (BiFC) assay and a multicolor BiFC assay to visualize protein-protein interactions in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16454041", "endSection": "abstract" } ] }, { "body": "Which pathological condition of the heart is known as hypertrophic cardiomyopathy (HCM)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25044876", "http://www.ncbi.nlm.nih.gov/pubmed/23782526", "http://www.ncbi.nlm.nih.gov/pubmed/25309450", "http://www.ncbi.nlm.nih.gov/pubmed/22665960", "http://www.ncbi.nlm.nih.gov/pubmed/21507890", "http://www.ncbi.nlm.nih.gov/pubmed/25328416", "http://www.ncbi.nlm.nih.gov/pubmed/25191275", "http://www.ncbi.nlm.nih.gov/pubmed/25209314", "http://www.ncbi.nlm.nih.gov/pubmed/25228955", "http://www.ncbi.nlm.nih.gov/pubmed/25081404" ], "ideal_answer": [ "Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young particularly among athletes. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins. HCM is the most prevalent genetic disorder affecting the heart and is typically inherited in an autosomal dominant pattern. Adults with cardiomyopathy suffer SCD or adverse events such as stroke and heart failure from HCM." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11984" ], "type": "summary", "id": "54dcb29dc0bb8dce23000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25328416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Familial hypertrophic cardiomyopathy (HCM), due to point mutations in genes for sarcomere proteins such as myosin, occurs in 1/500 people and is the most common cause of sudden death in young individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309450", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 689, "text": "n HCM, the modified protein function leads, over years to decades, to secondary remodeling with substantial morphological changes, such as hypertrophy, myofibrillar disarray, and extensive fibrosis associated with severe functional deterioration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in the young, particularly among athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228955", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 134, "text": "Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25209314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 522, "text": "Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy. The prevalence of phenotypic expression, in the absence of another systemic or cardiac disease causing increased left ventricular (LV) wall thickness, is estimated to be 1:500. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25081404", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 819, "text": "HCM is the most prevalent genetic disorder affecting the heart, it often goes undiagnosed until midlife after patients show symptoms of myocardial remodeling. Adults with cardiomyopathy suffer SCD or adverse events such as stroke and heart failure from HCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous autosomal dominant heart disease characterised by left ventricular hypertrophy in the absence of another cardiac or systemic disease that is capable of producing significant wall thickening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21507890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited genetic disease characterized by compensatory pathological left ventricle (LV) hypertrophy due to sarcomere dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665960", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 217, "text": "Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23782526", "endSection": "abstract" } ] }, { "body": "What is the genetic basis of Rubinstein-Taybi syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23432975", "http://www.ncbi.nlm.nih.gov/pubmed/16359492", "http://www.ncbi.nlm.nih.gov/pubmed/15706485", "http://www.ncbi.nlm.nih.gov/pubmed/20684013", "http://www.ncbi.nlm.nih.gov/pubmed/18773673", "http://www.ncbi.nlm.nih.gov/pubmed/22991675", "http://www.ncbi.nlm.nih.gov/pubmed/7630403", "http://www.ncbi.nlm.nih.gov/pubmed/14974086", "http://www.ncbi.nlm.nih.gov/pubmed/20689175", "http://www.ncbi.nlm.nih.gov/pubmed/22303793", "http://www.ncbi.nlm.nih.gov/pubmed/22269667" ], "ideal_answer": [ "Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder (prevalence 1:125,000) characterised by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa and short stature. The known genetic causes are a microdeletion at 16p13.3 or mutations or deletions of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) at 22q13 (5%). Direct sequencing of CREBBP performed in 13 RSTS patients identified the three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots. Thus about 55% of patients have cytogenetic or molecular abnormalities in the Crebbp or E1A binding protein p300 (Ep300) gene, leaving the diagnosis in 45% of patients to rest on clinical features only." ], "exact_answer": [ "Mutations or/and deletions in the genes of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) at 22q13 (5%)." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1933" ], "type": "factoid", "id": "516e5f41298dcd4e5100007f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7630403", "endSection": "sections.0" }, { "offsetInBeginSection": 173, "offsetInEndSection": 277, "text": "Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16p13.3", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7630403", "endSection": "sections.0" }, { "offsetInBeginSection": 314, "offsetInEndSection": 513, "text": "these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating as a co-activator in cyclic-AMP-regulated gene expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7630403", "endSection": "sections.0" }, { "offsetInBeginSection": 193, "offsetInEndSection": 351, "text": "RTS was shown to be associated with disruption of the CREB-binding protein gene CBP (CREBBP), either by gross chromosomal rearrangements or by point mutations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14974086", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15706485", "endSection": "title" }, { "offsetInBeginSection": 199, "offsetInEndSection": 348, "text": "A certain level of CREB-binding protein is essential for normal development, since inactivation of one allele causes Rubinstein-Taybi syndrome (RSTS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15706485", "endSection": "sections.0" }, { "offsetInBeginSection": 666, "offsetInEndSection": 737, "text": "In 92 patients, we were able to identify a total of 36 mutations in CBP", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15706485", "endSection": "sections.0" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1023, "text": "We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15706485", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Mutations in the CREBBP (CREB-binding protein gene) cause Rubinstein-Taybi syndrome (RSTS).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16359492", "endSection": "sections.0" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1242, "text": "Heterozygous CREBBP mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16359492", "endSection": "sections.0" }, { "offsetInBeginSection": 661, "offsetInEndSection": 756, "text": "It could be possible that genetic heterogeneity is related with novel mutations in other genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18773673", "endSection": "sections.0" }, { "offsetInBeginSection": 599, "offsetInEndSection": 680, "text": "identified a novel CREBBP missense mutation, c.2728A > G (predicting p.Thr910Ala)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20684013", "endSection": "sections.0" }, { "offsetInBeginSection": 730, "offsetInEndSection": 863, "text": "The p.Thr910Ala variant is outside the crucial histone acetyltransferase domain, and this may explain the mild and variable phenotype", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20684013", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Rubinstein-Taybi syndrome (RSTS), a developmental disorder comprising abnormalities that include mental retardation, an unusual facial appearance, broad thumbs and big toes is frequently associated with molecular lesions in the CREB-binding protein gene, CREBBP", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20689175", "endSection": "sections.0" }, { "offsetInBeginSection": 395, "offsetInEndSection": 595, "text": "Direct sequencing of CREBBP performed in 13 RSTS patients identified the three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots in which ten novel pathogenic mutations were localized", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20689175", "endSection": "sections.0" } ] }, { "body": "What is the function of the viral KP4 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7582897", "http://www.ncbi.nlm.nih.gov/pubmed/11901234", "http://www.ncbi.nlm.nih.gov/pubmed/21116630", "http://www.ncbi.nlm.nih.gov/pubmed/7966296", "http://www.ncbi.nlm.nih.gov/pubmed/10748529", "http://www.ncbi.nlm.nih.gov/pubmed/8145639", "http://www.ncbi.nlm.nih.gov/pubmed/17849147", "http://www.ncbi.nlm.nih.gov/pubmed/17522822", "http://www.ncbi.nlm.nih.gov/pubmed/8809749", "http://www.ncbi.nlm.nih.gov/pubmed/11532143", "http://www.ncbi.nlm.nih.gov/pubmed/21303448", "http://www.ncbi.nlm.nih.gov/pubmed/8616260" ], "ideal_answer": [ "The virally encoded fungal toxin KP4 specifically blocks L-type voltage-gated calcium channels." ], "concepts": [ "http://www.biosemantics.org/jochem#4265993", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014764", "http://www.uniprot.org/uniprot/KP4T_UMV4" ], "type": "summary", "id": "511a51331159fa8212000009", "snippets": [ { "offsetInBeginSection": 359, "offsetInEndSection": 381, "text": "antifungal protein KP4", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303448", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Killer protein 4 (KP4) is a well studied viral toxin secreted by the maize smut fungus Ustilago maydis that kills sensitive Ustilago strains as well as inhibits Fusarium and plant root growth by inhibiting calcium uptake.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21116630", "endSection": "sections.0" }, { "offsetInBeginSection": 390, "offsetInEndSection": 645, "text": "Our previous work on a virally encoded fungal toxin, KP4, from Ustilago maydis and subsequently with the plant defensin, MsDef1, from Medicago sativa demonstrated that some of these proteins specifically blocked calcium channels in both fungi and animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17849147", "endSection": "sections.0" }, { "offsetInBeginSection": 646, "offsetInEndSection": 838, "text": "The results presented here demonstrate that KP4 and three plant defensins, MsDef1, MtDef2, and RsAFP2, all inhibit root growth in germinating Arabidopsis seeds at low micromolar concentrations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17849147", "endSection": "sections.0" }, { "offsetInBeginSection": 148, "offsetInEndSection": 447, "text": ". There are three well-characterized killer toxins in U. maydis-KP1, KP4, and KP6-which are secreted by the P1, P4, and P6 subtypes, respectively. These killer toxins are small polypeptides encoded by segments of an endogenous, persistent double-stranded RNA (dsRNA) virus in each U. maydis subtype.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8809749", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The viral gene for the killer protein 4 (KP4) has been explored for its antifungal effect", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17522822", "endSection": "sections.0" }, { "offsetInBeginSection": 22, "offsetInEndSection": 81, "text": "antifungal protein KP4 from Ustilago maydis-infecting virus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10748529", "endSection": "sections.0" }, { "offsetInBeginSection": 399, "offsetInEndSection": 473, "text": "The antifungal activity correlated with the presence of the KP4 transgene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10748529", "endSection": "sections.0" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1078, "text": "These results suggest that KP4 may inhibit cell growth and division by blocking calcium-regulated signal transduction pathways.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11532143", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11532143", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11901234", "endSection": "sections.0" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1214, "text": "Our results defining the type of mammalian channel affected by this fungal toxin further support our contention that KP4 inhibits fungal growth by blocking transmembrane calcium flux through fungal calcium channels,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11901234", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Killer toxins are polypeptides secreted by some fungal species that kill sensitive cells of the same or related species. In the best-characterized cases, they function by creating new pores in the cell membrane and disrupting ion fluxes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8145639", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "KP4 is a virally encoded and highly specific toxin that kills fungi closely related to the fungus Ustilago maydis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7966296", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 167, "text": "The P4 strain of the corn smut fungus, Ustilago maydis, secretes a fungal toxin, KP4, encoded by a fungal virus (UMV4) that persistently infects its cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7582897", "endSection": "sections.0" }, { "offsetInBeginSection": 1307, "offsetInEndSection": 1438, "text": "These results led to experiments demonstrating that the toxin specifically inhibits voltage-gated Ca2+ channels in mammalian cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7582897", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Ustilago maydis killer toxins are small polypeptides (7-14 kDa) which kill susceptible cells of closely related fungal species. The KP4 toxin is a single polypeptide subunit with a molecular weight of 11.1 kDa", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8616260", "endSection": "sections.0" } ] }, { "body": "What is the function of the AIRE gene at the embryonic stage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21952165", "http://www.ncbi.nlm.nih.gov/pubmed/19302042", "http://www.ncbi.nlm.nih.gov/pubmed/19008896", "http://www.ncbi.nlm.nih.gov/pubmed/20226168", "http://www.ncbi.nlm.nih.gov/pubmed/22540148" ], "ideal_answer": [ "Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells. Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance. Knockdown of Aire in mouse ESCs resulted in significantly decreased clone-forming efficiency as well as attenuated cell cycle, suggesting Aire plays a role in ESC self-renewal. Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells.", "Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells.", "The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. Monitoring Aire expression in MSCs may thus be a critical parameter for clinical use." ], "exact_answer": [ "stem cell renewal and self-immune tolerance" ], "type": "factoid", "id": "56ed27012ac5ed145900000b", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 359, "text": "Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540148", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 496, "text": "we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540148", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 750, "text": "Instead, Aire reduced T cell mitochondrial reductase by negatively regulating a proinflammatory cytokine, early T cell activation factor (Eta)-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21952165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20226168", "endSection": "title" }, { "offsetInBeginSection": 557, "offsetInEndSection": 679, "text": "Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20226168", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 443, "text": "Mutations in the autoimmune regulator (AIRE) protein cause a breakdown of central tolerance that is associated with decreased expression of self antigens in the thymus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19008896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20226168", "endSection": "title" }, { "offsetInBeginSection": 167, "offsetInEndSection": 360, "text": "The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Aire promotes the self-renewal of embryonic stem cells through Lin28.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540148", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": " Abstract Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540148", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 497, "text": "The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Abstract Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540148", "endSection": "abstract" } ] }, { "body": "What is the principle of the PAR-CLIP methodology?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22152485", "http://www.ncbi.nlm.nih.gov/pubmed/21816340", "http://www.ncbi.nlm.nih.gov/pubmed/21559008", "http://www.ncbi.nlm.nih.gov/pubmed/22926237", "http://www.ncbi.nlm.nih.gov/pubmed/23706177", "http://www.ncbi.nlm.nih.gov/pubmed/21851591", "http://www.ncbi.nlm.nih.gov/pubmed/22213601", "http://www.ncbi.nlm.nih.gov/pubmed/23368412", "http://www.ncbi.nlm.nih.gov/pubmed/22844102", "http://www.ncbi.nlm.nih.gov/pubmed/20371350", "http://www.ncbi.nlm.nih.gov/pubmed/24297251", "http://www.ncbi.nlm.nih.gov/pubmed/22885304", "http://www.ncbi.nlm.nih.gov/pubmed/21572407", "http://www.ncbi.nlm.nih.gov/pubmed/20644507" ], "ideal_answer": [ "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. ", "A powerful cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs was termed PAR-CliP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation). PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions. It relies on the intracellular incorporation of photoactivatable ribonucleoside analogs into nascent transcripts, and yields characteristic sequence changes upon crosslinking that facilitate the separation of signal from noise.", "AR-CliP--a method to identify transcriptome-wide the binding sites of RNA binding proteinsOne characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. ", "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. ", "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins. PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions " ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722" ], "type": "summary", "id": "533c388dc45e133714000008", "snippets": [ { "offsetInBeginSection": 222, "offsetInEndSection": 371, "text": "We developed a cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20371350", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 567, "text": "To gain insight into the complexity of snoRNA processing and the functional relevance of snoRNA-derived small RNAs, we sequence long and short RNAs, small RNAs that co-precipitate with the Argonaute 2 protein and RNA fragments obtained in photoreactive nucleotide-enhanced crosslinking and immunoprecipitation (PAR-CLIP) of core snoRNA-associated proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23706177", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 441, "text": "A large amount of miRNA-target interactions (MTIs) have been identified by the crosslinking and immunoprecipitation (CLIP) and the photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) along with the next-generation sequencing (NGS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23368412", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 584, "text": "PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23368412", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 279, "text": "A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22152485", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 611, "text": "In this article, we review crosslinking and immunoprecipitation (CLIP) methods adapted for large-scale identification of target RNA-binding sites and the respective RNA recognition elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22213601", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 779, "text": "CLIP methods have the potential to detect hundreds of thousands of binding sites in single experiments although the separation of signal from noise can be challenging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22213601", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1184, "text": "We focus on photoactivatable ribonucleoside-enhanced CLIP, which relies on the intracellular incorporation of photoactivatable ribonucleoside analogs into nascent transcripts, and yields characteristic sequence changes upon crosslinking that facilitate the separation of signal from noise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22213601", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 184, "text": "Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844102", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 301, "text": "The strength of this versatile method results from induction of specific T to C transitions at sites of interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844102", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 343, "text": "PAR-CLIP reveals a collection of RNAs bound to a protein whereas SILAC-based RNA pull-downs identify a group of proteins bound to an RNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22885304", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 743, "text": "Here we present a step-by-step protocol and guidelines for the computational analysis for the large-scale identification of miRNA target sites in cultured cells by photoactivatable ribonucleoside enhanced crosslinking and immunoprecipitation (PAR-CLIP) of AGO proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22926237", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 233, "text": "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21851591", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 136, "text": "rosslinking and immunoprecipitation (CLIP) protocols have made it possible to identify transcriptome-wide RNA-protein interaction sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21851591", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 294, "text": "In this issue of Molecular Cell, Mukherjee et al. (2011) and Lebedeva et al. (2011) identify transcriptome-wide HuR-RNA interactions using PAR-CLIP, unveiling HuR's nuclear role in pre-mRNA processing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816340", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 130, "text": "ross-linking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21572407", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 373, "text": "We developed a method for CLIP data analysis, and applied it to compare CLIP with photoactivatable ribonucleoside-enhanced CLIP (PAR-CLIP) and to uncover how differences in cross-linking and ribonuclease digestion affect the identified sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21572407", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 905, "text": "In order to increase the specificity and positional resolution, a strategy referred to as CLIP (UV cross-linking and immunoprecipitation) was introduced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21559008", "endSection": "abstract" }, { "offsetInBeginSection": 1252, "offsetInEndSection": 1350, "text": "Recently, PAR-CLIP was introduced that uses photoreactive ribonucleoside analogs for cross-linking", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21559008", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 91, "text": "AR-CliP--a method to identify transcriptome-wide the binding sites of RNA binding proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644507", "endSection": "title" }, { "offsetInBeginSection": 1457, "offsetInEndSection": 1716, "text": "We developed a powerful cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs that we term PAR-CliP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644507", "endSection": "abstract" }, { "offsetInBeginSection": 1761, "offsetInEndSection": 1943, "text": "The method relies on the incorporation of photoreactive ribonucleoside analogs, such as 4-thiouridine (4-SU) and 6-thioguanosine (6-SG) into nascent RNA transcripts by living cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644507", "endSection": "abstract" }, { "offsetInBeginSection": 2303, "offsetInEndSection": 2477, "text": "One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644507", "endSection": "abstract" } ] }, { "body": "Which drugs are utilized to treat amiodarone-induced thyroitoxicosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16910349", "http://www.ncbi.nlm.nih.gov/pubmed/2781955", "http://www.ncbi.nlm.nih.gov/pubmed/19675515", "http://www.ncbi.nlm.nih.gov/pubmed/9217642", "http://www.ncbi.nlm.nih.gov/pubmed/12727944", "http://www.ncbi.nlm.nih.gov/pubmed/16544025", "http://www.ncbi.nlm.nih.gov/pubmed/7946779", "http://www.ncbi.nlm.nih.gov/pubmed/21135419", "http://www.ncbi.nlm.nih.gov/pubmed/11901034" ], "ideal_answer": [ "Amiodarone-induced thyrotoxicosis treatment includes anti-thyroid drugs and steroid therapy\nRadio Iodine Treatment (RIT) may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated.\nLithium is a useful and safe medication for treatment of iodine-induced thyrotoxicosis caused by amiodarone.\nThyrodectomy may be necessary in presence of unresponsiveness to standard medical treatments" ], "exact_answer": [ [ "Antithyroid drugs" ], [ "Corticosteroids" ], [ "Lithium" ], [ "Radioiodine" ] ], "type": "list", "id": "518cb4b5310faafe08000006", "snippets": [ { "offsetInBeginSection": 1462, "offsetInEndSection": 1517, "text": "good response to anti-thyroid drugs and steroid therapy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21135419", "endSection": "sections.0" }, { "offsetInBeginSection": 1813, "offsetInEndSection": 1986, "text": "The disease course of amiodarone-induced thyrotoxicosis is usually benign and remits with timely administration of anti-thyroid medications, with or without corticosteroids.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21135419", "endSection": "sections.0" }, { "offsetInBeginSection": 2852, "offsetInEndSection": 2982, "text": "RIT may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19675515", "endSection": "sections.0" }, { "offsetInBeginSection": 144, "offsetInEndSection": 262, "text": "Treatment consists in the use of a high dose of anti-thyroid drugs and steroids in an isolated form or in combination.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16544025", "endSection": "sections.0" }, { "offsetInBeginSection": 818, "offsetInEndSection": 968, "text": "the addition of lithium carbonate to the two other drugs resulted in a successful and safety therapy in controlling amiodarone-induced thyrotoxicosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16544025", "endSection": "sections.0" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1691, "text": "lithium is a useful and safe medication for treatment of iodine-induced thyrotoxicosis caused by amiodarone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9217642", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Two patients with amiodarone-induced thyrotoxicosis were treated successfully with potassium perchlorate and carbimazole while treatment with amiodarone was continued.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7946779", "endSection": "sections.0" }, { "offsetInBeginSection": 365, "offsetInEndSection": 545, "text": "Amiodarone-induced thyrotoxicosis seems to be a transient condition that can be treated successfully with a short course of antithyroid drugs without stopping amiodarone treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7946779", "endSection": "sections.0" }, { "offsetInBeginSection": 551, "offsetInEndSection": 643, "text": "Both patients were successfully treated with propylthiouracil (PTU) and dexamethasone (DXT).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2781955", "endSection": "sections.0" } ] }, { "body": "How is spastic diplegia diagnosed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2816867", "http://www.ncbi.nlm.nih.gov/pubmed/24901761", "http://www.ncbi.nlm.nih.gov/pubmed/15157997", "http://www.ncbi.nlm.nih.gov/pubmed/1743414", "http://www.ncbi.nlm.nih.gov/pubmed/23121133", "http://www.ncbi.nlm.nih.gov/pubmed/24409030", "http://www.ncbi.nlm.nih.gov/pubmed/17509240", "http://www.ncbi.nlm.nih.gov/pubmed/23085499", "http://www.ncbi.nlm.nih.gov/pubmed/25276040", "http://www.ncbi.nlm.nih.gov/pubmed/10427678", "http://www.ncbi.nlm.nih.gov/pubmed/7270517", "http://www.ncbi.nlm.nih.gov/pubmed/25700542", "http://www.ncbi.nlm.nih.gov/pubmed/2600179", "http://www.ncbi.nlm.nih.gov/pubmed/24239880", "http://www.ncbi.nlm.nih.gov/pubmed/21310339", "http://www.ncbi.nlm.nih.gov/pubmed/16344032", "http://www.ncbi.nlm.nih.gov/pubmed/17826455", "http://www.ncbi.nlm.nih.gov/pubmed/24182356", "http://www.ncbi.nlm.nih.gov/pubmed/20829081", "http://www.ncbi.nlm.nih.gov/pubmed/12549749" ], "ideal_answer": [ "Diagnosis of spastic diplegia is mainly carried out with through clinical gait analysis (CGA), with variations such as 1-minute walk, LSU, and 10-meter walk tests, or Gross Motor Function Measure-88 (GMFM-88). Other methods used for evaluation of patients include brain magnetic resonance imaging (MRI) and motor function, presence of epileptic episodes, and IQ or developmental quotient.", "Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of Hereditary Spastic Paraplegia (HSP) and Spastic Diplegia (SD). Argininaimia should be considered more frequently in the differential diagnosis of a patient with slowly progressive neurologic manifestations, especially progressive spastic diplegia. Gait Analysis (GA) complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10965" ], "type": "summary", "id": "56c3323a50c68dd416000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Spastic diplegia is the most common form of cerebral palsy worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25700542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Hereditary spastic paraplegia (HSP) and spastic diplegia (SD) patients share a strong clinical resemblance. Thus, HSP patients are frequently misdiagnosed with a mild form of SD. Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of HSP and SD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "The predominant clinical feature of patients with Hereditary Spastic Paraparesis (HSP) is gait disturbance owing to spasticity and weakness of the lower limbs; the spasticity in early-onset disease (infancy or childhood) often cannot be distinguished from mild form of spastic diplegia (SD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20829081", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 652, "text": "The aim of this study was to quantify the gait strategy in HSP and SD children, focusing on the differences between groups as concerns functional limitation during gait. 9 HSP and 16 SD children were evaluated using Gait Analysis; kinematic and kinetic parameters and EMG pattern during walking were identified and calculated to compare the two gait strategies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20829081", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 404, "text": "In contrast to other urea cycle disorders, hyperammonemic encephalopathy is rarely observed in patients with argininemia. Rather, most exhibit an insidious onset and progression of neurologic manifestations, including spastic diplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21310339", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 1005, "text": "We conclude that argininemia should be considered more frequently in the differential diagnosis of a patient with slowly progressive neurologic manifestations, especially progressive spastic diplegia, even in a population where argininemia was previously unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21310339", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 139, "text": "To assess the reliability and validity of a newly described classification of sagittal plane alignment in spastic diplegic gait.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16344032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "The objective of this prospective study was the application of proton magnetic resonance spectroscopy in children with spastic diplegia (SD) to determine the metabolite profile of SD children in the left basal ganglia, and to assess the relationship of this profile with motor and mental developmen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15157997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "The aim of this study was to establish the reliability and validity of visual gait assessment in children with spastic diplegia, who were community or household ambulators, using a modified version of the Physicians Rating Scale, known as the Observational Gait Scale (OGS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12549749", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 321, "text": "The aim of this study was to analyse quantitatively the gait of HSP and SD subjects in order to define the gait pattern in HSP and the differences between the two conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17509240", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 1044, "text": "This study shows that GA complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17509240", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 377, "text": "nstruct validity of the In-Hand Manipulation Test (IMT) by assessing the test's ability to discriminate between samples of children with and without known fine motor problems.METHOD: The IMT was administered to 55 children without known fine motor problems and 24 children with spastic diplegia who had mild to moderate fine motor problems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10427678", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 700, "text": "A discriminant analysis indicated that IMT total score correctly classified 83.33% of the participants as having or not having fine motor problems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10427678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Calcaneal gait or deformity can be a significant complication after heel cord lengthening. After heel cord lengthening, 20 children with spastic diplegia were evaluated by gait analysis to define calcaneal gait objectively and describe associated morbidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2600179", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 464, "text": "Significant differences were found in birth weight, birth head circumference, and the one-minute Apgar score", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7270517", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 709, "text": " Intracranial hemorrhage and neonatal seizures occurred significantly more often in infants with SD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7270517", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 690, "text": "On the Movement Assessment of Infants at 4 months of age, the children with hemiplegia and quadriplegia showed significantly higher risk scores than the nonhandicapped group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2816867", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1097, "text": "At 1 year of age, however, the Bayley Motor Scale was extremely sensitive in picking up motor deficits in children with all three types of cerebral palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2816867", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 848, "text": "Hip flexion combined with knee extension (leg elevation) and isolated knee movements were not seen in diplegic infants, but were seen in all control preterm infants with a good prognosis, after five and six months corrected age, respectively. The absence of these movements is a useful diagnostic item for spastic diplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1743414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Full body gait analysis may improve diagnostic discrimination between hereditary spastic paraplegia and spastic diplegia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085499", "endSection": "title" }, { "offsetInBeginSection": 179, "offsetInEndSection": 557, "text": "Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of HSP and SD. Previous analysis has focused on the lower-body but not the upper-body, where numerous compensations during walking occur. The aim of this study was to compare the full-body movements of HSP and SD groups and, in particular, the movement of the upper limbs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085499", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 526, "text": "The study subjects were eight patients with spastic diplegia and eight normal children. Three-dimensional gait analysis was used for the survey. The measured gait variables were the joints of the lower extremity in the sagittal plane, frontal plane, and transverse planes and the maximum and minimum angles of their stance phase and swing phases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25276040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Relationships between spasticity, strength, gait, and the GMFM-66 in persons with spastic diplegia cerebral palsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17826455", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "[Purpose] This study aimed to investigate the effects of Vojta therapy on spatiotemporal gait parameters in children with spastic diplegia. [Methods] The study population consisted of 3 children diagnosed with spastic diplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24409030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "The aim of this study was to explore the physical status and gait patterns of children with spastic diplegia secondary to human immunodeficiency virus encephalopathy (HIVE). A cross-sectional study was conducted on children diagnosed with HIVE and spastic diplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24182356", "endSection": "abstract" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1264, "text": "The results demonstrated that HSP patients used more spine movement to compensate for lower limb movement alterations, whereas SD patients used their arms for compensation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085499", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 205, "text": "To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23121133", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 239, "text": "To examine the validity and clinical utility of functional assessments (1-minute walk test, 10-meter walk test, Timed Up&Go [TUG] test, Timed Up and Down Stairs [TUDS]test, sit-to-stand [STS] test, and lateral step-up [LSU]test)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24239880", "endSection": "abstract" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1958, "text": "These functional assessments (1-minute walk, LSU, and 10-meter walk tests) are simple to administer, quick, low cost, and user-friendly. Although these assessments are not a substitute for the criterion standard (GMFM-88), they may be used for a quick assessment in adolescents with cerebral palsy (levels I-III) either at school or during rehabilitation, especially when time is limited", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24239880", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 255, "text": "The aim of this study was to evaluate the effect of dynamic bilateral postural stability on balance control and gait parameters in children with cerebral palsy.DESIGN: Thirty children with spastic diplegia (8-10 yrs) were included in this study", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24901761", "endSection": "abstract" } ] }, { "body": "Which is the genetic defect causing Neurofibromatosis type 1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16835897", "http://www.ncbi.nlm.nih.gov/pubmed/16323217", "http://www.ncbi.nlm.nih.gov/pubmed/21567923", "http://www.ncbi.nlm.nih.gov/pubmed/14722917", "http://www.ncbi.nlm.nih.gov/pubmed/2129297" ], "ideal_answer": [ "Neurofibromatosis type 1 (NF1) is due to all types of mutations in the neurofibromin (NF1) gene." ], "exact_answer": [ "Mutation in NF1 gene." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025542", "http://www.uniprot.org/uniprot/NF1_RAT", "http://www.disease-ontology.org/api/metadata/DOID:0050325", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016514", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009456", "http://www.uniprot.org/uniprot/NF1_HUMAN", "http://www.uniprot.org/uniprot/NF1_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020022", "http://www.disease-ontology.org/api/metadata/DOID:8712", "http://www.uniprot.org/uniprot/NF1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:630", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820" ], "type": "factoid", "id": "52f223e02059c6d71c00000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Neurofibromatosis type 1 and Noonan syndrome are both common genetic disorders with autosomal dominant inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21567923", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1086, "text": "Molecular analysis showed a missense mutation in exon 25 of the NF1 gene (4288A>G, p.N1430D)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21567923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16835897", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of caf\u00e9-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16835897", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 1207, "text": "Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frame-shift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16835897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome affecting approximately 1 in 4,000 persons. It is an autosomal-dominant disorder with half of the cases resulting from spontaneous mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16323217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Characterization of the somatic mutational spectrum of the neurofibromatosis type 1 (NF1) gene in neurofibromatosis patients with benign and malignant tumors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14722917", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 1026, "text": "Ninety-one tumors from 31 NF1 patients were screened for gross changes in the NF1 gene using microsatellite/restriction fragment length polymorphism (RFLP) markers; loss of heterozygosity (LOH) was found in 17 out of 91 (19%) tumors (including two out of seven MPNSTs). Denaturing high performance liquid chromatography (DHPLC) was then used to screen 43 LOH-negative and 10 LOH-positive tumors for NF1 microlesions at both RNA and DNA levels. Thirteen germline and 12 somatic mutations were identified, of which three germline (IVS7-2A>G, 3731delT, 6117delG) and eight somatic (1888delG, 4374-4375delCC, R2129S, 2088delG, 2341del18, IVS27b-5C>T, 4083insT, Q519P) were novel. A mosaic mutation (R2429X) was also identified in a neurofibroma by DHPLC analysis and cloning/sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14722917", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 736, "text": "The region of DNA located between two translocation breakpoints has been cloned and a DNA sequence encoding a 11-13 kb mRNA identified. That this sequence shows deletions and point mutations in NF1 affected individuals and not in normal controls provides strong evidence that it is indeed the NF1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2129297", "endSection": "abstract" } ] }, { "body": "Which is the human selenoprotein that contains several Se-Cys residues?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10692426", "http://www.ncbi.nlm.nih.gov/pubmed/15777501", "http://www.ncbi.nlm.nih.gov/pubmed/11122377", "http://www.ncbi.nlm.nih.gov/pubmed/7637580", "http://www.ncbi.nlm.nih.gov/pubmed/19345254", "http://www.ncbi.nlm.nih.gov/pubmed/20417644", "http://www.ncbi.nlm.nih.gov/pubmed/17000762", "http://www.ncbi.nlm.nih.gov/pubmed/9288402", "http://www.ncbi.nlm.nih.gov/pubmed/15104205" ], "ideal_answer": [ "Selenoprotein P, that contains 10 selenocysteines." ], "exact_answer": [ "Selenoprotein P" ], "concepts": [ "http://www.biosemantics.org/jochem#4275372", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051149", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051140" ], "type": "factoid", "id": "5343caffaeec6fbd07000002", "snippets": [ { "offsetInBeginSection": 453, "offsetInEndSection": 547, "text": "selenoprotein P and several other selenoproteins are known to contain multiple selenocysteines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417644", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 226, "text": "Sepp1) is a secreted protein that is made up of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19345254", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 447, "text": "selenoprotein P genes encode multiple UGAs and two SECIS elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17000762", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 117, "text": "Human selenoprotein P (HSelP) is unique protein that contains 10 selenocysteines encoded by 10 inframe UGA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15777501", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 93, "text": "SeP) is an extracellular glycoprotein with 8-10 selenocysteines per molecule", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15104205", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 305, "text": "human, bovine and rodent selenoprotein P genes encode proteins containing 10-12 selenocysteines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11122377", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 197, "text": "Selenoprotein P is unique in that its mRNA encodes 10-12 selenocysteine residues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10692426", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 561, "text": "The deduced polypeptide sequence comprises 380 residues including ten selenocysteines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9288402", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 147, "text": "selenoprotein-P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9288402", "endSection": "abstract" }, { "offsetInBeginSection": 44, "offsetInEndSection": 103, "text": "selenoprotein P-like protein containing 12 selenocysteines ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7637580", "endSection": "title" }, { "offsetInBeginSection": 236, "offsetInEndSection": 308, "text": " rat and human selenoprotein P cDNA but contained 12 rather than 10 TGAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7637580", "endSection": "abstract" } ] }, { "body": "Which package is available for analysing genomic interactions in R/Bioconductor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23671339" ], "ideal_answer": [ "r3Cseq is an R/Bioconductor package designed to perform 3C-seq data analysis in a number of different experimental designs. The package reads a common aligned read input format, provides data normalization, allows the visualization of candidate interaction regions and detects statistically significant chromatin interactions, thus greatly facilitating hypothesis generation and the interpretation of experimental results." ], "exact_answer": [ "r3Cseq" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009693" ], "type": "factoid", "id": "56a39d60496b62f23f000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "r3Cseq: an R/Bioconductor package for the discovery of long-range genomic interactions from chromosome conformation capture and next-generation sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23671339", "endSection": "title" }, { "offsetInBeginSection": 596, "offsetInEndSection": 1097, "text": "We present r3Cseq, an R/Bioconductor package designed to perform 3C-seq data analysis in a number of different experimental designs. The package reads a common aligned read input format, provides data normalization, allows the visualization of candidate interaction regions and detects statistically significant chromatin interactions, thus greatly facilitating hypothesis generation and the interpretation of experimental results. We further demonstrate its use on a series of real-world applications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23671339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "r3Cseq: an R/Bioconductor package for the discovery of long-range genomic interactions from chromosome conformation capture and next-generation sequencing data", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23671339", "endSection": "title" } ] }, { "body": "How many clinical trials for off-label drugs in neonates are cited in the literature.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20821198" ], "ideal_answer": [ "There are no reports on clinical trials of off-label drugs in neonates. An analysis of Pediatric Investigation Plans submitted between 2007 and 2010 shows that neonates were included in the study of 4 products, but it is unknown if the trial drugs are off-label and if the trials are being conducted at all." ], "exact_answer": [ "none", "0", "zero" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056687", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017326", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016032", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007231", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018849" ], "type": "factoid", "id": "5150b807d24251bc05000072", "snippets": [ { "offsetInBeginSection": 459, "offsetInEndSection": 1195, "text": "Of the 17 Paediatric Investigation Plans submitted, 14 have resulted in an EMA Decision, 3 were withdrawn by the applicants, 8 were granted a full waiver from development, and 1 resulted in a negative opinion. Decisions as issued included 15 clinical trials, with at least 1,282 children to be recruited into studies across five different products. Neonates were included in four of the products. CONCLUSIONS: The small number of submissions indicates a lack of new drugs being developed for the management of pain. Ethical concerns that too many vulnerable children will be recruited into clinical trials must be balanced against limiting the number of off-label prescribing and obtaining age-appropriate information on paediatric use.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20821198", "endSection": "sections.0" }, { "offsetInBeginSection": 298, "offsetInEndSection": 449, "text": "Paediatric Investigations Plans (PIPs) submitted with a Decision (outcome) reached between September 2007 and March 2010 were included in the analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20821198", "endSection": "sections.0" } ] }, { "body": "Are stress granules involved in the pathogenesis of Amyotrophic Lateral Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23474818", "http://www.ncbi.nlm.nih.gov/pubmed/24297750", "http://www.ncbi.nlm.nih.gov/pubmed/24013423", "http://www.ncbi.nlm.nih.gov/pubmed/22405725", "http://www.ncbi.nlm.nih.gov/pubmed/23257289", "http://www.ncbi.nlm.nih.gov/pubmed/24312274", "http://www.ncbi.nlm.nih.gov/pubmed/23629963", "http://www.ncbi.nlm.nih.gov/pubmed/21173160", "http://www.ncbi.nlm.nih.gov/pubmed/20699327", "http://www.ncbi.nlm.nih.gov/pubmed/25429138", "http://www.ncbi.nlm.nih.gov/pubmed/20674093", "http://www.ncbi.nlm.nih.gov/pubmed/20606625", "http://www.ncbi.nlm.nih.gov/pubmed/24920614", "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "http://www.ncbi.nlm.nih.gov/pubmed/26557057", "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "http://www.ncbi.nlm.nih.gov/pubmed/24336168", "http://www.ncbi.nlm.nih.gov/pubmed/25216585", "http://www.ncbi.nlm.nih.gov/pubmed/23152885", "http://www.ncbi.nlm.nih.gov/pubmed/19765185" ], "ideal_answer": [ "Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis. ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism.", "Yes, stress granules (SGs) have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0034063", "http://amigo.geneontology.org/amigo/term/GO:0097165", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000690", "http://www.disease-ontology.org/api/metadata/DOID:332", "http://amigo.geneontology.org/amigo/term/GO:0035617" ], "type": "yesno", "id": "56c81fd15795f9a73e00000c", "snippets": [ { "offsetInBeginSection": 333, "offsetInEndSection": 544, "text": "SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26557057", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 624, "text": "Like several other ALS-associated proteins, CREST is recruited to induced stress granules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1453, "text": "Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 250, "text": "A unifying feature of many proteins associated with ALS, including TDP-43 and ataxin-2, is that they localize to stress granules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336168", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 292, "text": "Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23629963", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 796, "text": "Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as part of its normal function, might be coopted during disease pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23629963", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 507, "text": "Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 586, "text": "Fused in sarcoma (FUS) belongs to the group of RNA-binding proteins implicated as underlying factors in amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. Multiple FUS gene mutations have been linked to hereditary forms, and aggregation of FUS protein is believed to play an important role in pathogenesis of these diseases. In cultured cells, FUS variants with disease-associated amino acid substitutions or short deletions affecting nuclear localization signal (NLS) and causing cytoplasmic mislocalization can be sequestered into stress granules (SGs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920614", "endSection": "title" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1529, "text": "Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920614", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 897, "text": "Furthermore, in response to oxidative stress or heat shock conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type FUS, assembled into perinuclear stress granules in proportion to their cytoplasmic expression levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20699327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20699327", "endSection": "title" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1150, "text": "Our results suggest that the ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20674093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257289", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "TDP-43 is an RNA-binding protein linked to amyotrophic lateral sclerosis (ALS) that is known to regulate the splicing, transport, and storage of specific mRNAs into stress granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25429138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons and glia, where it associates with stress granules (SGs) and forms large inclusions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24312274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20699327", "endSection": "title" }, { "offsetInBeginSection": 650, "offsetInEndSection": 793, "text": "Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297750", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 474, "text": "Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21173160", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 605, "text": "We found that in response to oxidative stress and to environmental insults of different types TDP-43 is capable to assemble into stress granules (SGs), ribonucleoprotein complexes where protein synthesis is temporarily arrested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19765185", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1233, "text": "Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20606625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "endSection": "title" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1236, "text": "Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20606625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216585", "endSection": "title" }, { "offsetInBeginSection": 322, "offsetInEndSection": 437, "text": "However, the role of autophagy in regulation of FUS-positive stress granules (SGs) and aggregates remains unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216585", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 874, "text": "Although co-localized primarily in the nucleus in normal condition, FUS/TLS and PRMT1 were partially recruited to the cytoplasmic granules under oxidative stress, which were merged with stress granules (SGs) markers in SH-SY5Y cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The effect of PRMT1-mediated arginine methylation on the subcellular localization, stress granules, and detergent-insoluble aggregates of FUS/TLS", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152885", "endSection": "title" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1320, "text": "Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22405725", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1305, "text": "These findings support a two-hit hypothesis, whereby cytoplasmic mislocalization of FUS protein, followed by cellular stress, contributes to the formation of cytoplasmic aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474818", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 779, "text": "Here, we exploited a Drosophila model of ALS and neuronal cell lines to elucidate the role of the RNA-binding ability of FUS in regulating FUS-mediated toxicity, cytoplasmic mislocalization and incorporation into stress granules (SGs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Stress granules as crucibles of ALS pathogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23629963", "endSection": "title" } ] }, { "body": "Does TGF-beta play a role in cardiac regeneration after myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12374778", "http://www.ncbi.nlm.nih.gov/pubmed/23293297", "http://www.ncbi.nlm.nih.gov/pubmed/18985280", "http://www.ncbi.nlm.nih.gov/pubmed/17322368", "http://www.ncbi.nlm.nih.gov/pubmed/19966054", "http://www.ncbi.nlm.nih.gov/pubmed/22513374", "http://www.ncbi.nlm.nih.gov/pubmed/15883211", "http://www.ncbi.nlm.nih.gov/pubmed/10198196", "http://www.ncbi.nlm.nih.gov/pubmed/16842199" ], "ideal_answer": [ "TGF\u03b2 signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016212", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ], "type": "yesno", "id": "52f5083d2059c6d71c00001e", "snippets": [ { "offsetInBeginSection": 768, "offsetInEndSection": 1034, "text": "We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor \u03b2 signaling pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23293297", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 477, "text": "Here, we report that the balance between the reparative and regenerative processes is achieved through Smad3-dependent TGF\u03b2 signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513374", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1529, "text": "Thus, TGF\u03b2 signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513374", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1558, "text": "As expected, transforming growth factor (TGF)-beta, a profibrotic cytokine, was dramatically upregulated in MI hearts, but its phosphorylated comediator (pSmad) was significantly downregulated in the nuclei of Cx43-deficient hearts post-MI, suggesting that downstream signaling of TGF-beta is diminished substantially in Cx43-deficient hearts. This diminution in profibrotic TGF-beta signaling resulted in the attenuation of adverse structural remodeling as assessed by echocardiography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19966054", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1230, "text": "Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-beta(1). Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18985280", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 760, "text": "After injury, the presence of macrophages, which secreted high levels of transforming growth factor-beta and vascular endothelial growth factor-A, led to rapid removal of cell debris and replacement by granulation tissue containing inflammatory cells and blood vessels, followed by myofibroblast infiltration and collagen deposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17322368", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1037, "text": "Secretion of transforming growth factor-beta and vascular endothelial growth factor-A as well as neovascularization, myofibroblast infiltration, and collagen deposition decreased. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17322368", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1181, "text": "Repression of proinflammatory cytokine and chemokine synthesis, mediated in part through Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10, is critical for resolution of the inflammatory infiltrate and transition to fibrous tissue deposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16842199", "endSection": "abstract" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 2026, "text": "TGF-beta conducted the myogenic differentiation of CD117+ stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-beta-preprogrammed CD117+ cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15883211", "endSection": "abstract" }, { "offsetInBeginSection": 1593, "offsetInEndSection": 1790, "text": "These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10198196", "endSection": "abstract" } ] }, { "body": "Is there a genetic component for happiness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26060713", "http://www.ncbi.nlm.nih.gov/pubmed/19728071", "http://www.ncbi.nlm.nih.gov/pubmed/20981772", "http://www.ncbi.nlm.nih.gov/pubmed/23769682", "http://www.ncbi.nlm.nih.gov/pubmed/24690898", "http://www.ncbi.nlm.nih.gov/pubmed/20397744", "http://www.ncbi.nlm.nih.gov/pubmed/22885141", "http://www.ncbi.nlm.nih.gov/pubmed/19569406", "http://www.ncbi.nlm.nih.gov/pubmed/20440640" ], "ideal_answer": [ "Results of studies on genetic factors indicated an average effectiveness of genetic about 35 -50 percent on happiness. The MAOA gene predicts happiness in women. The heritability of happiness was estimated at 22% for males and 41% in females." ], "type": "summary", "id": "56cf413f3975bb303a000009", "snippets": [ { "offsetInBeginSection": 895, "offsetInEndSection": 1083, "text": "inally, a systematic review performed based on existing information. Results of studies on genetic factors indicated an average effectiveness of genetic about 35 -50 percent on happiness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26060713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "The MAOA gene predicts happiness in women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22885141", "endSection": "title" }, { "offsetInBeginSection": 164, "offsetInEndSection": 310, "text": "Although twin studies estimate that genetic factors account for 35-50% of the variance in human happiness, knowledge of specific genes is limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22885141", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 531, "text": "This investigation examines association between happiness and monoamine oxidase A (MAOA) genotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22885141", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 371, "text": "Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other ones involving severe developmental handicap. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981772", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 473, "text": "The heritability of happiness was estimated at 22% for males and 41% in females. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20397744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Biometric studies have shown that happiness is strongly affected by genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20440640", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1145, "text": "The clustering of the four different measures (quality of life in general, satisfaction with life, quality of life at present, and subjective happiness) was explained by an underlying additive genetic factor and an underlying non-additive genetic factor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728071", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 379, "text": " happiness and the environment are influenced by genetic factors and family upbringing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19569406", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 815, "text": "The results suggest that many putative indicators of the environment are highly heritable and, indeed, that the same genes that affect the environment may affect happiness as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19569406", "endSection": "abstract" } ] }, { "body": "What enzyme is inhibied by Opicapone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24271646", "http://www.ncbi.nlm.nih.gov/pubmed/23336248", "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "http://www.ncbi.nlm.nih.gov/pubmed/23248072", "http://www.ncbi.nlm.nih.gov/pubmed/24925090" ], "ideal_answer": [ "Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease" ], "exact_answer": [ "catechol-O-methyltransferase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ], "type": "factoid", "id": "56c1d857ef6e394741000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24271646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "OBJECTIVE: The present study aimed at evaluating the effect of opicapone, a third generation nitrocatechol catechol-O-methyltransferase (COMT) inhibitor, on the systemic and central bioavailability of 3,4-dihydroxy-l-phenylalanine (levodopa) and related metabolites in the cynomolgus monkey.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1563, "text": "CONCLUSIONS: Opicapone behaved as long-acting COMT inhibitor that markedly increased systemic and central levodopa bioavailability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925090", "endSection": "abstract" }, { "offsetInBeginSection": 2232, "offsetInEndSection": 2467, "text": "CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248072", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925090", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 325, "text": "The purpose of this study was to evaluate the tolerability, pharmacokinetics (including the effect of food) and pharmacodynamics (effect on COMT activity) following single oral doses of opicapone in young healthy male volunteers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "AIMS: The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23336248", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1350, "text": "CONCLUSION: Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23336248", "endSection": "abstract" }, { "offsetInBeginSection": 2079, "offsetInEndSection": 2171, "text": "Opicapone demonstrated marked and sustained inhibition of erythrocyte soluble COMT activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248072", "endSection": "abstract" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1597, "text": "The long duration of COMT inhibition by opicapone, however, tended to be independent from the dose taken.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248072", "endSection": "abstract" } ] }, { "body": "What kind of affinity purification would you use in order to isolate soluble lysosomal proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15789345", "http://www.ncbi.nlm.nih.gov/pubmed/16709564", "http://www.ncbi.nlm.nih.gov/pubmed/18507433", "http://www.ncbi.nlm.nih.gov/pubmed/17258946", "http://www.ncbi.nlm.nih.gov/pubmed/18370023", "http://www.ncbi.nlm.nih.gov/pubmed/16145712", "http://www.ncbi.nlm.nih.gov/pubmed/11079561", "http://www.ncbi.nlm.nih.gov/pubmed/16399764", "http://www.ncbi.nlm.nih.gov/pubmed/18977398", "http://www.ncbi.nlm.nih.gov/pubmed/19383612", "http://www.ncbi.nlm.nih.gov/pubmed/22158965" ], "ideal_answer": [ "The rationale for purification of the soluble lysosomal proteins resides in their characteristic sugar, the mannose-6-phosphate (M6P), which allows an easy purification by affinity chromatography on immobilized M6P receptors." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000345", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008247", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005764", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002846" ], "type": "summary", "id": "5140569623fec90375000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Most luminal lysosomal proteins are synthesized as precursors containing mannose 6-phosphate (Man6-P) and a number of recent studies have conducted affinity purification of Man6-P containing proteins as a step toward defining the composition of the lysosome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18507433", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "This chapter describes the process of production, purification, separation, and mass spectrometry identification of soluble lysosomal proteins. The rationale for purification of these proteins resides in their characteristic sugar, the mannose-6-phosphate (M6P), which allows an easy purification by affinity chromatography on immobilized M6P receptor (MPR", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18370023", "endSection": "sections.0" }, { "offsetInBeginSection": 419, "offsetInEndSection": 616, "text": "ecretions of these cells were affinity purified using an affinity matrix derivatized with MPR46 and MPR300. In the protein fraction bound to the affinity matrix and eluted with mannose 6-phosphate,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16145712", "endSection": "sections.0" }, { "offsetInBeginSection": 643, "offsetInEndSection": 850, "text": "Proteins containing mannose 6-phosphate (Man6-P), a carbohydrate modification used for targeting resident soluble lysosomal proteins to the lysosome, were affinity-purified using immobilized Man6-P receptor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15789345", "endSection": "sections.0" }, { "offsetInBeginSection": 710, "offsetInEndSection": 784, "text": ". We purified mannose 6-phosphorylated proteins by affinity chromatography", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19383612", "endSection": "sections.0" }, { "offsetInBeginSection": 683, "offsetInEndSection": 852, "text": "Since lysosomal soluble proteins are characterized by the presence of mannose-6-phosphate, they were purified on an affinity support bearing mannose-6-phosphate receptor", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11079561", "endSection": "sections.0" }, { "offsetInBeginSection": 617, "offsetInEndSection": 744, "text": "The most abundant lysosomal substrates of Acp2 and Acp5 were identified by Man6P affinity chromatography and mass spectrometry.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22158965", "endSection": "sections.0" }, { "offsetInBeginSection": 761, "offsetInEndSection": 834, "text": "urinary proteins were affinity purified on immobilized Man-6-P receptors,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17258946", "endSection": "sections.0" }, { "offsetInBeginSection": 212, "offsetInEndSection": 391, "text": "A number of proteomic studies have focused on lysosomal proteins, exploiting the fact that Man-6-P-containing forms can be purified by affinity chromatography on immobilized MPRs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16399764", "endSection": "sections.0" }, { "offsetInBeginSection": 463, "offsetInEndSection": 589, "text": "In this study, we purified the Man-6-P glycoforms of proteins from human plasma by affinity chromatography on immobilized MPRs", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16709564", "endSection": "sections.0" } ] }, { "body": "Which are the genes thought to be regulated by EWS/FLI?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "http://www.ncbi.nlm.nih.gov/pubmed/18927503", "http://www.ncbi.nlm.nih.gov/pubmed/15492248", "http://www.ncbi.nlm.nih.gov/pubmed/19920188", "http://www.ncbi.nlm.nih.gov/pubmed/23527175", "http://www.ncbi.nlm.nih.gov/pubmed/17114343" ], "ideal_answer": [ "The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of a significant number of genes are affected in Ewing sarcoma, some of which are known to be directly or indirectly regulated by EWS/FLI. Such genes are BCL11B, NRoB1, GSTM4, NKX2.2 and p53." ], "exact_answer": [ [ "BCL11B" ], [ "NRoB1" ], [ "GSTM4" ], [ "NKX2.2" ], [ "p53" ] ], "type": "list", "id": "552faa43bc4f83e828000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527175", "endSection": "title" }, { "offsetInBeginSection": 123, "offsetInEndSection": 549, "text": "EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma, however, it is unknown which of these genes contribute to the transformed phenotype. Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527175", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 705, "text": "BCL11B, a zinc finger transcription factor, acts as a transcriptional repressor in Ewing's sarcoma and contributes to the EWS/FLI repressed gene signature", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527175", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 539, "text": "EWS/FLI functions as an aberrant transcription factor to regulate genes that mediate the oncogenic phenotype of Ewing's sarcoma. One of these regulated genes, NR0B1, encodes a corepressor protein, and likely plays a transcriptional role in tumorigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "GSTM4 is a microsatellite-containing EWS/FLI target involved in Ewing's sarcoma oncogenesis and therapeutic resistance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 407, "text": "We recently showed that EWS/FLI regulates one of its key targets, NR0B1, through a GGAA-microsatellite in its promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 856, "text": "We found that EWS/FLI directly binds the GSTM4 promoter, and regulates GSTM4 expression through a GGAA-microsatellite in its promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1092, "text": "The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17114343", "endSection": "abstract" }, { "offsetInBeginSection": 1203, "offsetInEndSection": 1313, "text": "We validated NR0B1 as an EWS/FLI-dysregulated gene and confirmed its expression in primary human tumor samples", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17114343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "endSection": "title" }, { "offsetInBeginSection": 523, "offsetInEndSection": 653, "text": "Functional analysis revealed that NKX2.2 is an EWS/FLI-regulated gene that is necessary for oncogenic transformation in this tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 989, "text": "Neuroblastoma-Ews/Fli-1 infectant cell lines showed marked increases in p53 protein expression without transcriptional up-regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15492248", "endSection": "abstract" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1804, "text": "We then tested the p53 response pathway and observed that the neuroblastoma parent cells responded to genotoxic stress, whereas the neuroblastoma-Ews/Fli-1 infectants did not. These results suggest that Ews/Fli-1 can directly abrogate the p53 pathway to promote tumorigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15492248", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 741, "text": "We recently showed that EWS/FLI interacts with GGAA-microsatellites to regulate some of its target genes, including NR0B1, an EWS/FLI-regulated gene that is required for the oncogenic phenotype of Ewings sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18927503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527175", "endSection": "title" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1093, "text": "The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17114343", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 549, "text": "Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527175", "endSection": "abstract" } ] }, { "body": "Do archaeal genomes contain one or multiple origins of replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15197606", "http://www.ncbi.nlm.nih.gov/pubmed/20850498", "http://www.ncbi.nlm.nih.gov/pubmed/16249118", "http://www.ncbi.nlm.nih.gov/pubmed/2541880", "http://www.ncbi.nlm.nih.gov/pubmed/16321966", "http://www.ncbi.nlm.nih.gov/pubmed/24185008", "http://www.ncbi.nlm.nih.gov/pubmed/22978470", "http://www.ncbi.nlm.nih.gov/pubmed/16980466", "http://www.ncbi.nlm.nih.gov/pubmed/11967086", "http://www.ncbi.nlm.nih.gov/pubmed/20667100", "http://www.ncbi.nlm.nih.gov/pubmed/17350933", "http://www.ncbi.nlm.nih.gov/pubmed/18922777", "http://www.ncbi.nlm.nih.gov/pubmed/14526006", "http://www.ncbi.nlm.nih.gov/pubmed/23375370", "http://www.ncbi.nlm.nih.gov/pubmed/15876567", "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "http://www.ncbi.nlm.nih.gov/pubmed/17511521", "http://www.ncbi.nlm.nih.gov/pubmed/11521661", "http://www.ncbi.nlm.nih.gov/pubmed/17956224", "http://www.ncbi.nlm.nih.gov/pubmed/15337158", "http://www.ncbi.nlm.nih.gov/pubmed/21784908", "http://www.ncbi.nlm.nih.gov/pubmed/20978102", "http://www.ncbi.nlm.nih.gov/pubmed/12646230", "http://www.ncbi.nlm.nih.gov/pubmed/22942672", "http://www.ncbi.nlm.nih.gov/pubmed/12237132", "http://www.ncbi.nlm.nih.gov/pubmed/22812406", "http://www.ncbi.nlm.nih.gov/pubmed/17392430" ], "ideal_answer": [ "Some archaea replicate from single origins but most archaea and all eukaryotes replicate using multiple origins.", "Multiple functional sites of origin of replication may exist in the genomes of most archaea. This has only been demonstrated recently. Two studies have shown that multiple origins of replication function in two archaeal species." ], "exact_answer": [ "mostly multiple", "Multiple" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006270", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006260", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020745", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018741", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001105", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051738", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003688" ], "type": "factoid", "id": "52fe58f82059c6d71c00007a", "snippets": [ { "offsetInBeginSection": 1056, "offsetInEndSection": 1407, "text": "Therefore, these lines of evidence strongly suggest that the identified region is a replication origin, which is designated as oriC1. The analysis of the y component of the Z curve, i.e., MK disparity curve, suggests the presence of another replication origin corresponding to one of the peaks in the MK disparity curve at around 1,388 kb of the genom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15197606", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1039, "text": "Our results strongly suggest that the single replication origin of M. mazei is situated at the intergenic region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12237132", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 424, "text": "Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185008", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 95, "text": "multiple DNA replication origins are a hallmark of Eukaryotes and some Archaea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23375370", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 509, "text": "Multiple orc/cdc6-associated replication origins were predicted in all of the analyzed haloarchaeal genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22978470", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 822, "text": "different replication origins in some archaeal genomes leave quite different patterns of strand asymmetry", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22942672", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 301, "text": "the single chromosome of Pyrobaculum calidifontis contains four replication origins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22812406", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 569, "text": "six archaeal genomes from the genus Sulfolobus containing three origins of replication were selected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978102", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 835, "text": "The strong replication-biased structuring of the Sulfolobus chromosome implies that the multiple replication origins serve purposes other than simply shortening the time required for replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20667100", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 295, "text": "The 3 DNA replication origins of Sulfolobus acidocaldarius", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18922777", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 665, "text": "We have used a combination of genetic, biochemical, and bioinformatic approaches to map DNA replication origins in H. volcanii. Five autonomously replicating sequences were found adjacent to cdc6/orc1 genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17511521", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 427, "text": "the multiple replication origin paradigm has also been demonstrated within the archaeal domain of life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17392430", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 132, "text": "multiple chromosome replication origins in Sulfolobus species has added yet another eukaryotic trait to the archaea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16249118", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 434, "text": "We employed Z-curve analysis to identify one replication origin in the Methanocaldococcus jannaschii genome, two replication origins in the Halobacterium species NRC-1 genome and one replication origin in the Methanosarcina mazei genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15876567", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 245, "text": "Archaea seem to replicate using a single origin (as do eubacteria) even though archaeal replication factors are more like those of eukaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11521661", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 877, "text": "Based on the above analysis, a model of replication of Halobacterium NRC-1 with two replication origins and two termini has been proposed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12646230", "endSection": "abstract" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1285, "text": "In addition, the potential multiple replication origins of the archaeon Sulfolobus solfataricus are suggested by the analysis based on the Z curve method", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12646230", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "While multiple replication origins have been observed in archaea, considerably less is known about their evolutionary processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22978470", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1680, "text": "multiple orc/cdc6-associated replication origins in haloarchaeal genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22978470", "endSection": "abstract" } ] }, { "body": "Which pathological conditions are caused by mutations in the CYLD gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16922728", "http://www.ncbi.nlm.nih.gov/pubmed/23426135", "http://www.ncbi.nlm.nih.gov/pubmed/20132422", "http://www.ncbi.nlm.nih.gov/pubmed/12190880", "http://www.ncbi.nlm.nih.gov/pubmed/19730223", "http://www.ncbi.nlm.nih.gov/pubmed/18806492", "http://www.ncbi.nlm.nih.gov/pubmed/21598248", "http://www.ncbi.nlm.nih.gov/pubmed/21552290", "http://www.ncbi.nlm.nih.gov/pubmed/21389835", "http://www.ncbi.nlm.nih.gov/pubmed/21345146", "http://www.ncbi.nlm.nih.gov/pubmed/20838385", "http://www.ncbi.nlm.nih.gov/pubmed/15541090", "http://www.ncbi.nlm.nih.gov/pubmed/20972631", "http://www.ncbi.nlm.nih.gov/pubmed/20151946", "http://www.ncbi.nlm.nih.gov/pubmed/21577203", "http://www.ncbi.nlm.nih.gov/pubmed/20607853", "http://www.ncbi.nlm.nih.gov/pubmed/19917957", "http://www.ncbi.nlm.nih.gov/pubmed/17851586", "http://www.ncbi.nlm.nih.gov/pubmed/15024746", "http://www.ncbi.nlm.nih.gov/pubmed/23694822", "http://www.ncbi.nlm.nih.gov/pubmed/22077640", "http://www.ncbi.nlm.nih.gov/pubmed/19668078", "http://www.ncbi.nlm.nih.gov/pubmed/23641715", "http://www.ncbi.nlm.nih.gov/pubmed/19076795", "http://www.ncbi.nlm.nih.gov/pubmed/23404581", "http://www.ncbi.nlm.nih.gov/pubmed/19911186", "http://www.ncbi.nlm.nih.gov/pubmed/17083363" ], "ideal_answer": [ "Since loss of CYLD expression can be observed in different types of human cancer, it is now well established that CYLD acts as a tumor suppressor gene. Pathogenic mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma. CYLD expression has also been reported to be dramatically downregulated in basal cell carcinoma (BCC), the most common cancer in humans." ], "exact_answer": [ [ "Brooke-Spiegler syndrome", "BSS" ], [ "Cylindromatosis" ], [ "Multiple Familial Trichoepithelioma", "MFT" ] ], "concepts": [ "http://www.uniprot.org/uniprot/CYLD_BOVIN", "http://www.uniprot.org/uniprot/CYLD_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.uniprot.org/uniprot/CYLD_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010336", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/CYLD_HUMAN", "http://www.uniprot.org/uniprot/CYLD_PONAB" ], "type": "list", "id": "533c3af6c45e13371400000d", "snippets": [ { "offsetInBeginSection": 948, "offsetInEndSection": 1176, "text": "We detected a frameshift mutation in the CYLD gene, designated 2253delG, underlying the disorder and were able to show that a single mutation can result in distinct clinical and histologic expression in familial cylindromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12190880", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 728, "text": "Previously, a candidate MTF locus has been mapped to 9p21 while disease gene for familial cylindromatosis, the CYLD gene located on 16q21-13 has been identified", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15024746", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 848, "text": "Here, we show that mutations in the CYLD gene are also the genetic basis for three different Chinese families with MFT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15024746", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 284, "text": "familial trichoepithelioma (MFT) and familial cylindromatosis are two clinically distinct cancer syndromes. MFT patients developed mostly trichoepithelioma in the face while cylindromatosis patients developed cylindromas predominantly (approximately 90%) on the head and neck", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15024746", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 120, "text": "phenotype of familial cylindromatosis associated with an R758X nonsense mutation in the CYLD tumour suppressor gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15541090", "endSection": "title" }, { "offsetInBeginSection": 288, "offsetInEndSection": 410, "text": "We describe a family with cylindromatosis, in which affected individuals have an inherited R758X nonsense mutation of CYLD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15541090", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 116, "text": "YLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16922728", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 440, "text": "We describe a single family with affected members exhibiting either the FC or the MFT phenotypes associated with a mutation in the CYLD gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16922728", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 202, "text": "ndividuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21552290", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 120, "text": "YLD is a tumor-suppressor gene mutated in the skin appendage tumors cylindromas, trichoepitheliomas, and spiradenomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23426135", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1230, "text": "In addition, we have characterized Maspin downregulation in cylindromas, trichoepitheliomas, and spiradenomas carrying functional inactivating mutations of CYLD, also providing an evidence of the correlation between impaired CYLD function and Maspin decreased expression in vivo in human tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23426135", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 262, "text": "Germ\u2011line mutation in cylindromatosis (CYLD), a tumor suppressor gene, causes familial cylindromatosis and Brook\u2011Spiegler syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404581", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 271, "text": "atients carrying heterozygous germline truncating mutations in the CYLD gene develop multiple primary hair follicle-related tumours. A highly patterned tumour, termed cylindroma, and a highly disorganized tumour, termed spiradenoma, may both develop in the same patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21598248", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 139, "text": "ultiple trichoepitheliomas associated with a novel heterozygous mutation in the CYLD gene as an adjunct to the histopathological diagnosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23694822", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 145, "text": "ultiple trichoepitheliomas (TEs), especially in the familial setting, have been associated with germline heterozygous mutations in the CYLD gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23694822", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 726, "text": "We describe a 35-year-old woman with multiple facial TEs, in whom the molecular genetic analysis revealed a novel heterozygous c.1843delT mutation in the CYLD gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23694822", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 930, "text": "This frameshift mutation was also present in a heterozygous state in the TE tumor cells. The demonstration of a novel CYLD mutation was used as an adjunct to the histopathological diagnosis in this case", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23694822", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 92, "text": "novel germline mutation in the CYLD gene in a Slovak patient with Brooke-Spiegler syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23641715", "endSection": "title" }, { "offsetInBeginSection": 627, "offsetInEndSection": 793, "text": "This new germline mutation in the CYLD gene of a Slovak patient with Brooke-Spiegler syndrome extends the catalogue of known CYLD germline mutations in this condition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23641715", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 625, "text": "Molecular biologic study of the CYLD gene performed from the peripheral blood identified a novel splice site c.2041+1 G>T mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23641715", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 422, "text": "Patients with Brooke-Spiegler syndrome have various mutations in the CYLD gene, a tumor-suppressor gene located on chromosome 16q", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22077640", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 258, "text": "Mutation and loss of heterozygosity of the CYLD gene causes development of cylindromatosis, a benign tumour originating from the skin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21577203", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 390, "text": "Our study shows that CYLD expression is dramatically downregulated in basal cell carcinoma (BCC), the most common cancer in humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21577203", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 415, "text": "Although some early studies suggested a role for the PTCH gene on chromosome 9q22.3 in the etiopathogenesis of MFT, recent studies of occasional patients with the MFT clinical phenotype identified mutations in the CYLD gene on chromosome 16q12-q13, a gene responsible for BSS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21389835", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 551, "text": "Since loss of CYLD expression can be observed in different types of human cancer, it is now well established that CYLD acts as a tumor suppressor gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21345146", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 164, "text": "mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20972631", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 298, "text": "we demonstrate that the expression in tumorigenic epidermal cells of a catalytically inactive form of CYLD (CYLD(C/S)) that mimics the identified mutations of cyld in human tumors and competes with the endogenous CYLD results in enhanced cell proliferation and inhibition of apoptosi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20838385", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1351, "text": "In contrast with previous studies showing the development of benign tumors by mutations in the CYLD gene, here we provide evidence that the occurrence of mutations in the CYLD gene in tumorigenic epidermal cells (carrying previous mutations) increases the aggressiveness of carcinomas, mainly through enhancement of the expression of angiogenic factors, having therefore a key role in epidermal cancer malignancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20838385", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 926, "text": "By interphase cytogenetics, a (sub)clonal biallelic CYLD deletion was observed by interphase cytogenetics in 1 of 29 primary cHL, whereas signal patterns indicating decreased CYLD copy numbers were observed in a total of 10 of 29 primary cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20607853", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 75, "text": "mutation in the CYLD gene within a family with Brooke-Spiegler syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20151946", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 179, "text": "rooke-Spiegler syndrome is a rare, autosomal dominant disease characterized by multiple skin appendage tumors caused by various mutations in the CYLD gene on chromosome 16q12-q13", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20151946", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 160, "text": "authors report a case of Brooke-Spiegler syndrome (BSS) with a novel germline CYLD mutation and various somatic mutations identified in the lesional tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20132422", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 486, "text": "he available histopathological material included 24 trichoepitheliomas, 2 large nodular basal cell carcinomas (BCCs), 2 spiradenomas, 1 spiradenocylindroma and 1 trichoblastoma composed of large and small nodules with prominent clear cell differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20132422", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 417, "text": "To comprehensively ascertain the extent and severity of clinical features in affected individuals from 2 large families with proven heterozygous mutations in the CYLD locus and to correlate these findings with the 3 appendageal tumor predisposition syndromes (familial cylindromatosis, Brooke-Spiegler syndrome, and multiple familial trichoepitheliomas) known to be associated with such germline mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19917957", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 323, "text": "In this report, we identified a novel mutation of CYLD gene in a Chinese family with MFT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19911186", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 178, "text": "case of Brooke-Spiegler syndrome with a novel germline deep intronic mutation in the CYLD gene leading to intronic exonization, diverse somatic mutations, and unusual histology", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19668078", "endSection": "title" }, { "offsetInBeginSection": 3, "offsetInEndSection": 133, "text": "present a case of Brooke-Spiegler syndrome with a germline deep intronic mutation in the CYLD gene leading to intronic exonization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19668078", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 763, "text": "A deep intronic mutation resulting in exonization and a somatic sequence mutations causing exon skipping are hitherto unreported genetic mechanisms involving the CYLD gene in patients with Brooke-Spiegler syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19668078", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 105, "text": "novel splicing mutation of the CYLD gene in a Taiwanese family with multiple familial trichoepithelioma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19076795", "endSection": "title" }, { "offsetInBeginSection": 144, "offsetInEndSection": 264, "text": "Mutations in the CYLD gene, which is also the gene responsible for familial cylindromatosis, have been reported recently", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19076795", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 634, "text": "We report a novel splicing mutation (IVS12 + 1 G-->A) in the CYLD gene in a Taiwanese pedigree with MFT, and discuss new developments in treatment options", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19076795", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 133, "text": "new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17851586", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 237, "text": "rooke-Spiegler syndrome, familial cylindromatosis, and familial trichoepithelioma are autosomal-dominant genetic predispositions for benign tumors of skin appendages caused by mutations in the CYLD gene localized on chromosome 16q12-q13", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17851586", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 252, "text": "The disease gene was mapped to 16q12-13, and mutations in the CYLD gene were identified in families with BSS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17083363", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 920, "text": "By sequence analysis, we identified a recurrent mutation 2272C>T (R758X) of the CYLD gene in the affected individuals of this family, which was previously identified in other ethnic families with familial cylindromatosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17083363", "endSection": "abstract" } ] }, { "body": "Which is the genetic basis of Spinal Muscular Atrophy (SMA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19062530", "http://www.ncbi.nlm.nih.gov/pubmed/22628388", "http://www.ncbi.nlm.nih.gov/pubmed/11442327", "http://www.ncbi.nlm.nih.gov/pubmed/9731538", "http://www.ncbi.nlm.nih.gov/pubmed/22323744", "http://www.ncbi.nlm.nih.gov/pubmed/12220455", "http://www.ncbi.nlm.nih.gov/pubmed/12115944", "http://www.ncbi.nlm.nih.gov/pubmed/9073029", "http://www.ncbi.nlm.nih.gov/pubmed/10339583", "http://www.ncbi.nlm.nih.gov/pubmed/17076267", "http://www.ncbi.nlm.nih.gov/pubmed/19646678", "http://www.ncbi.nlm.nih.gov/pubmed/20225030" ], "ideal_answer": [ "The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1). Mutations of the SMN1 gene are responsible for SMA. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. A critical question is why only the homozygous loss of SMN1, and not SMN2, results in spinal muscular atrophy (SMA). H4F5 is also highly deleted in type I SMA chromosomes, and thus is a candidate phenotypic modifier for SMA.\nThe molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1)." ], "exact_answer": [ "The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009133", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009134", "http://www.disease-ontology.org/api/metadata/DOID:767", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001284" ], "type": "factoid", "id": "56c5fd325795f9a73e000005", "snippets": [ { "offsetInBeginSection": 192, "offsetInEndSection": 437, "text": "Mutations in TRPV4, encoding a cation channel, have recently been identified in one large dominant congenital spinal muscular atrophy kindred, but the genetic basis of dominant congenital spinal muscular atrophy in many families remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22628388", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 1339, "text": "We report clinical, electrophysiology, muscle magnetic resonance imaging and histopathology findings in a four generation family with typical dominant congenital spinal muscular atrophy features, without mutations in TRPV4, and in whom linkage to other known dominant neuropathy and spinal muscular atrophy genes has been excluded. The autopsy findings in the proband, who died at 14 months of age from an unrelated illness, provided a rare opportunity to study the neuropathological basis of dominant congenital spinal muscular atrophy. There was a redu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22628388", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 452, "text": "Recently, the common forms of spinal muscular atrophy (SMA) have been associated with mutations of the SMN and NAIP genes on chromosome 5, in the region q11.2-13.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9073029", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 649, "text": "Some correlation has been established between SMN protein levels and disease course; nevertheless, the genetic basis for SMA phenotypic variability remains unclear, and it has been postulated that the loss of an additional modifying factor contributes to the severity of type I SMA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731538", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 893, "text": "Using comparative genomics to screen for such a factor among evolutionarily conserved sequences between mouse and human, we have identified a novel transcript, H4F5, which lies closer to SMN1 than any previously identified gene in the region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731538", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1150, "text": "A multi-copy microsatellite marker that is deleted in more than 90% of type I SMA chromosomes is embedded in an intron of this gene, indicating that H4F5 is also highly deleted in type I SMA chromosomes, and thus is a candidate phenotypic modifier for SMA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10339583", "endSection": "title" }, { "offsetInBeginSection": 65, "offsetInEndSection": 181, "text": "A critical question is why only the homozygous loss of SMN1, and not SMN2, results in spinal muscular atrophy (SMA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10339583", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1103, "text": "Thus, the failure of SMN2 to fully compensate for SMN1 and protect from SMA is due to a nucleotide exchange (C/T) that attenuates activity of an exonic enhancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10339583", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 535, "text": "Autosomal recessive childhood proximal SMA is the commonest form and is due to mutations in a gene encoding a novel protein, SMN, that appears to play a critical role in RNA metabolism but has also been shown to interact with actin-binding proteins and mediators of programmed cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11442327", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 319, "text": "Mutations of the SMN1 gene are responsible for SMA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12115944", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 773, "text": "All patients were found to be homozygous for the loss of either exon 7 or exons 7 and 8 of the SMN1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12220455", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 946, "text": "Six additional patients had anterior horn cell disease but were negative for the SMN1 gene deletion. All six had exclusion features listed in the international guidelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12220455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17076267", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 475, "text": "The structures of the SMN1 gene and SMN2 pseudogene, mutations distorting the SMN1 function, the structure and functions of the Smn neurotrophic protein, its role in biogenesis of small nuclear ribonucleoproteins (snRNPs), and the principles and prdblems of molecular diagnosis in SMA are described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19062530", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 250, "text": "SMA are caused by mutations of the survival of motor neuron gene (SMN1) leading to a reduction of the SMN protein amount.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225030", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 886, "text": "From a better knowledge of the genetic basis of SMA and the defects resulting from the mutations of SMN1 in cellular or animal models, several therapeutics strategies have been selected aiming at targeting SMN2, a partially functional copy of SMN1 gene which remains present in patients, or to prevent neurons from death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225030", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 690, "text": "We used a homozygosity mapping and positional cloning approach in a consanguineous family of Ashkenazi Jewish origin and identified a nonsense mutation in the vaccinia-related kinase 1 gene (VRK1) as a cause of SMA-PCH", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19646678", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 838, "text": "SMN1 and SMN2 quantification was undertaken to investigate the genotype-phenotype relationship.RESULTS: Two novel point mutations were identified in exon 3 of SMN1 (p.Tyr130Cys and p.Tyr130His) in the highly conserved Tudor domain of the Smn protein.CONCLUSIONS: The genetic basis of SMA in the rare cases of compound heterozygous carriers of SMN1 deletions is complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22323744", "endSection": "abstract" } ] }, { "body": "Which are the common symptoms of Cushing's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24062268", "http://www.ncbi.nlm.nih.gov/pubmed/17322955" ], "ideal_answer": [ "Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension." ], "exact_answer": [ [ "weight gain" ], [ "growth retardation" ], [ "hirsutism" ], [ "obesity" ], [ "striae" ], [ "acne" ], [ "hypertension" ] ], "type": "list", "id": "571f3b320fd6f91b68000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. The most common cause of Cushing syndrome in children and adolescents is exogenous administration of glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24062268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "This is a rare syndrome and its main endocrine manifestation, primary pigmented nodular adrenal disease (PPNAD), is an uncommon cause of adrenocorticotropic hormone-independent Cushing's syndrome.We report the case of a 20-year-old patient with a history of weight gain, hirsutism, acne, secondary amenorrhea and facial lentiginosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17322955", "endSection": "abstract" } ] }, { "body": "Which is the third subunit of the TSC1-TSC2 complex upstream of mTORC1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22795129" ], "ideal_answer": [ "TBC1D7 was identified as a stably associated and ubiquitous third core subunit of the TSC1-TSC2 complex. It was demonstrated that TSC1-TSC2-TBC1D7 (TSC-TBC) is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity to negatively regulate mTORC1 activity. In agreement with this, TBC1D7 knockdown was shown to result in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions." ], "exact_answer": [ "TBC1D7" ], "concepts": [ "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.biosemantics.org/jochem#4266396", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031931", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ], "type": "factoid", "id": "5319ac99b166e2b806000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex, which limits cell growth in response to poor growth conditions. Through its GTPase-activating protein (GAP) activity toward Rheb, this complex inhibits the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a key promoter of cell growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795129", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 633, "text": "Here, we identify and biochemically characterize TBC1D7 as a stably associated and ubiquitous third core subunit of the TSC1-TSC2 complex. We demonstrate that the TSC1-TSC2-TBC1D7 (TSC-TBC) complex is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795129", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 894, "text": "TBC1D7 knockdown decreases the association of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization of TSC2 to the lysosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795129", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1072, "text": "Like the other TSC-TBC components, TBC1D7 knockdown results in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795129", "endSection": "abstract" } ] }, { "body": "Which kinase is inhibited by the small molecule KN-93?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17457979", "http://www.ncbi.nlm.nih.gov/pubmed/16896952", "http://www.ncbi.nlm.nih.gov/pubmed/14749212", "http://www.ncbi.nlm.nih.gov/pubmed/9864285", "http://www.ncbi.nlm.nih.gov/pubmed/10712242", "http://www.ncbi.nlm.nih.gov/pubmed/22290426", "http://www.ncbi.nlm.nih.gov/pubmed/11827960", "http://www.ncbi.nlm.nih.gov/pubmed/11164895", "http://www.ncbi.nlm.nih.gov/pubmed/11248432", "http://www.ncbi.nlm.nih.gov/pubmed/7690557", "http://www.ncbi.nlm.nih.gov/pubmed/8939965", "http://www.ncbi.nlm.nih.gov/pubmed/21187407", "http://www.ncbi.nlm.nih.gov/pubmed/9596994", "http://www.ncbi.nlm.nih.gov/pubmed/15175389", "http://www.ncbi.nlm.nih.gov/pubmed/15569687", "http://www.ncbi.nlm.nih.gov/pubmed/1662507" ], "ideal_answer": [ "The calcium/calmodulin-dependent protein kinase-II (CaMK-II) is inhibited by the small molecule KN-93. KN-93 is a membrane-permeant calcium/calmodulin- dependent kinase II (CaMK-II)-selective inhibitor" ], "exact_answer": [ "The calcium/calmodulin-dependent protein kinase-II", "CaM kinase II", "CAMK2" ], "concepts": [ "http://www.biosemantics.org/jochem#4263678", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007266" ], "type": "factoid", "id": "54f89e1a06d9727f76000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective inhibitor, induces apoptosis in some lines of human tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22290426", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 707, "text": "Knockdown of \u03b2CaMKII by lentiviral-mediated expression of shRNA prevented the synaptic inactivity-induced increase in GluA1, as did treatment with the CaM kinase inhibitor KN-93, but not the inactive analog KN-92.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187407", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 167, "text": "To investigate the effects of KN-93, a CaMKII selective inhibitor on cell proliferation and the expression of p53 or p21 protein in human hepatic stellate cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17457979", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1113, "text": "Injection of the CaM kinase inhibitor KN-93 into pupae resulted in a reduced number of antennal lobe glial cells migrating into the neuropil to form borders around glomeruli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16896952", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1172, "text": "In contrast, addition of the intracellular Ca2+ chelator BAPTA-AM or the Ca2+/calmodulin-dependent (CaM) kinase inhibitor KN93 blocked reporter gene activation in response to IH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15569687", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 761, "text": "These increases in CPEB phosphorylation were attenuated by a specific peptide inhibitor of CaMKII and by the general CaM-kinase inhibitor KN-93.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15175389", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1141, "text": "Alternatively, treatment with KN-93, a selective inhibitor of CaMKII activation, or adenoviral overexpression of kinase-negative CaMKII-delta(2), inhibited ATP-dependent activation of ERK1/2 but had no effect on PDBu- or PDGF-stimulated ERK1/2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14749212", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 569, "text": "Ca(2+)/CaM-dependent protein kinase inhibitor KN-93 also blocked zygote elongation, while its ineffective analog KN-92 did not have such effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11827960", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 416, "text": "CaM kinase inhibitor KN93 on its own exhibits little toxicity up to 10 mM, as measured by release of lactate dehydrogenase (LDH) into the culture medium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11248432", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 586, "text": "To further elucidate the mechanism by which calcium-induced ERK activation occurs, we used the CaM-kinase inhibitor KN-93 and an inactive analog of KN-93 (KN-92).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11164895", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 598, "text": "Hearts were pretreated with the CaM kinase inhibitor KN-93 or the inactive analog KN-92 (0.5 microM) for 10 min before clofilium exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9864285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The calmodulin-dependent protein kinase-II (CaMK-II) inhibitor KN-93 has been shown to reversibly arrest mouse and human cells in the G1 phase of the cell cycle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9596994", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1009, "text": "NE-induced MAP kinase and cPLA2 activation was also inhibited in cells treated with a CaM kinase II inhibitor, KN-93, or with CaM kinase II antisense oligonucleotide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8939965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "A novel Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) inhibitor, KN-93 potently inhibits gastric acid secretion from parietal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7690557", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 735, "text": "CaM kinase II activation was inhibited by KN-93 pretreatment (IC(50) approximately 1 microM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10712242", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1164, "text": "In vitro, KN-93 potently inhibited rabbit myocardial CaM kinase activity (calculated Ki", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9864285", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 850, "text": "KN-93 also inhibited the autophosphorylation of both the alpha- and beta-subunits of CaMKII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1662507", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 734, "text": "CaM kinase II activation was inhibited by KN-93 pretreatment (IC(50) approximately 1 microM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10712242", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1238, "text": "In vitro, KN-93 potently inhibited rabbit myocardial CaM kinase activity (calculated Ki 100 microM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9864285", "endSection": "abstract" } ] }, { "body": "What is the effect of Chk2 splice variants on wild-type Chk2 kinase activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20080130" ], "ideal_answer": [ "Chk2 splice variants have been demonstrated to exert a dominant-negative effect on wild-type Chk2 kinase activity." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064447", "http://www.uniprot.org/uniprot/CHK2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043549", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008380", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020033", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016301" ], "type": "summary", "id": "5357bd56f1005d6b58000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Chk2 splice variants express a dominant-negative effect on the wild-type Chk2 kinase activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080130", "endSection": "title" }, { "offsetInBeginSection": 661, "offsetInEndSection": 1130, "text": "Here we evaluated the function of four Chk2 splice proteins for which mRNA splice variants were identified in human breast carcinomas. These splice variants were stably expressed as nuclear proteins. Two splice forms (Chk2Delta4 and Chk2del(2-3)) expressed kinase activity while variants Chk2Delta11 and Chk2isoI were essentially kinase inactive. Independent of intrinsic kinase activity, each splice variant impaired wild-type Chk2 activity through heterodimerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080130", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1262, "text": "we suggest alternative splicing as a possible novel mechanism for repression of the Chk2 wild-type function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Chk2 splice variants express a dominant-negative effect on the wild-type Chk2 kinase activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080130", "endSection": "title" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1130, "text": "Independent of intrinsic kinase activity, each splice variant impaired wild-type Chk2 activity through heterodimerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080130", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1129, "text": "Independent of intrinsic kinase activity, each splice variant impaired wild-type Chk2 activity through heterodimerization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080130", "endSection": "abstract" } ] }, { "body": "List genes that have been found mutated in CMT1A (Charcot-Marie-Tooth disease type 1 A).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25522693", "http://www.ncbi.nlm.nih.gov/pubmed/25430934", "http://www.ncbi.nlm.nih.gov/pubmed/24819634", "http://www.ncbi.nlm.nih.gov/pubmed/25500726", "http://www.ncbi.nlm.nih.gov/pubmed/25400662", "http://www.ncbi.nlm.nih.gov/pubmed/25385046", "http://www.ncbi.nlm.nih.gov/pubmed/25519680", "http://www.ncbi.nlm.nih.gov/pubmed/25429913", "http://www.ncbi.nlm.nih.gov/pubmed/25150498" ], "ideal_answer": [ "PMP22 is the common gene found mutated through a duplication in CMT1A. Other genes are\nMPZ and SH3TC2" ], "exact_answer": [ [ "PMP22" ], [ "MPZ" ], [ "SH3TC2" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10595", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002607" ], "type": "list", "id": "54d65b6b3706e8952800000c", "snippets": [ { "offsetInBeginSection": 26, "offsetInEndSection": 77, "text": "Most cases of CMT are caused by mutations in PMP22,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25522693", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 196, "text": " structural myelin protein PMP22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25519680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Duplication of the gene encoding the peripheral myelin protein of 22 kDa (PMP22) underlies the most common inherited neuropathy, Charcot-Marie-Tooth 1A (CMT1A), a disease without a known cure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25150498", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1085, "text": ". Two patients showed rearrangements in the PMP22 gene, which is commonly associated with CMT1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24819634", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 290, "text": "Many PMP22 mutants accumulate in excess in the endoplasmic reticulum (ER) and lead to the inherited neuropathies of Charcot-Marie-Tooth (CMT) disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25385046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400662", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 794, "text": "In CMT1, PMP22 duplication was the most common mutation while the second gene in order of frequency was MPZ in familial and SH3TC2 in isolated cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25429913", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 762, "text": "CMT1A/PMP22 duplication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430934", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 287, "text": "he most frequent subtype is type 1A (CMT1A) caused by duplication in chromosome 17p12 that includes PMP22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25500726", "endSection": "abstract" } ] }, { "body": "Which viruses are best known to cause myocarditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18039618", "http://www.ncbi.nlm.nih.gov/pubmed/18277927", "http://www.ncbi.nlm.nih.gov/pubmed/2641165", "http://www.ncbi.nlm.nih.gov/pubmed/14993139", "http://www.ncbi.nlm.nih.gov/pubmed/3889351", "http://www.ncbi.nlm.nih.gov/pubmed/8199011" ], "ideal_answer": [ "The most frequent viruses causing myocarditis are Enterovirus, Adenovirus and Coxsackie B viruses." ], "exact_answer": [ [ "Enterovirus" ], [ "Adenovirus" ], [ "Coxsackie B virus" ] ], "type": "list", "id": "517a8c918ed59a060a000043", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 183, "text": "Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18277927", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 147, "text": "Enteroviruses have been considered to be the most common cause of acute myocarditis and possible consequence of dilated cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18039618", "endSection": "sections.0" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1116, "text": "n our study the adenovirus genome was found to be the most frequent virus genome in explanted heart tissues.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18039618", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Coxsackie B viruses (types 1 to 5) are the most frequent reported cause of acute viral myocarditis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3889351", "endSection": "sections.0" } ] }, { "body": "Which genes have been associated with Cerebral Cavernous Malformation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25122144", "http://www.ncbi.nlm.nih.gov/pubmed/24287896", "http://www.ncbi.nlm.nih.gov/pubmed/20592472", "http://www.ncbi.nlm.nih.gov/pubmed/24466005", "http://www.ncbi.nlm.nih.gov/pubmed/16100539", "http://www.ncbi.nlm.nih.gov/pubmed/12877753", "http://www.ncbi.nlm.nih.gov/pubmed/12172908", "http://www.ncbi.nlm.nih.gov/pubmed/24990152", "http://www.ncbi.nlm.nih.gov/pubmed/14697511", "http://www.ncbi.nlm.nih.gov/pubmed/12140362", "http://www.ncbi.nlm.nih.gov/pubmed/24251678", "http://www.ncbi.nlm.nih.gov/pubmed/16465592", "http://www.ncbi.nlm.nih.gov/pubmed/26246098", "http://www.ncbi.nlm.nih.gov/pubmed/11310633", "http://www.ncbi.nlm.nih.gov/pubmed/25451273", "http://www.ncbi.nlm.nih.gov/pubmed/15543491", "http://www.ncbi.nlm.nih.gov/pubmed/25086949", "http://www.ncbi.nlm.nih.gov/pubmed/24481819" ], "ideal_answer": [ "Loss-of-function mutations in genes encoding CCM1 (also known as KRIT1), CCM2 (also known as OSM and malcavernin) or CCM3 (also known as PDCD10) cause cerebral cavernous malformations (CCMs)." ], "exact_answer": [ [ "CCM1/KRIT1" ], [ "CCM2/OSM/Malcavernin" ], [ "CCM3/PDCD10" ] ], "type": "list", "id": "571f2b5bbb137a4b0c000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26246098", "endSection": "title" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1150, "text": "we outline a consistent association between PDCD10 mutations and a syndrome of CCMs with multiple meningiomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26246098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Cerebral cavernous malformation (CCM) is a disease of vascular malformations known to be caused by mutations in one of three genes: CCM1, CCM2 or CCM3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990152", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 189, "text": "To study the molecular genetic and clinical features of cerebral cavernous malformations (CCM) in a cohort of Spanish patients.METHODS: We analyzed the CCM1, CCM2, and CCM3 genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24466005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Loss-of-function mutations in genes encoding KRIT1 (also known as CCM1), CCM2 (also known as OSM and malcavernin) or PDCD10 (also known as CCM3) cause cerebral cavernous malformations (CCMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24481819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Surveying genetic variants and molecular phylogeny of cerebral cavernous malformation gene, CCM3/PDCD10", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451273", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The three cerebral cavernous malformations (CCMs) genes namely CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10 have been identified for which mutations cause cerebral cavernous malformations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451273", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 888, "text": "At least 45% of families affected with cerebral cavernous malformations harbour a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1, CCM1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14697511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Mutations in Krev1 interaction trapped gene 1 (KRIT1) cause cerebral cavernous malformation, an autosomal dominant disease featuring malformation of cerebral capillaries resulting in cerebral hemorrhage, strokes, and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12140362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12140362", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11310633", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15543491", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16465592", "endSection": "title" }, { "offsetInBeginSection": 766, "offsetInEndSection": 877, "text": "These findings document a de novo germline mutation in Kritl gene that causes cerebral cavernous malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11310633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Cerebral cavernous malformation is a common human vascular disease that arises due to loss-of-function mutations in genes encoding three intracellular adaptor proteins, cerebral cavernous malformations 1 protein (CCM1), CCM2, and CCM3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Cerebral cavernous malformation is a common human vascular disease that arises due to loss-of-function mutations in genes encoding three intracellular adaptor proteins, cerebral cavernous malformations 1 protein (CCM1), CCM2, and CCM3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12172908", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12877753", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Loss-of-function mutations in CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10 genes are identified in the vast majority of familial cases with multiple cerebral cavernous malformations (CCMs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251678", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 490, "text": "Mutations in three genes are associated with CCM. These genes encode for the proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations 1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3 (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell death 10 (CCM3/PDCD10).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24287896", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 705, "text": "At least 45% of families affected with cerebral cavernous malformations harbour a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14697511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25122144", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A novel CCM1 mutation associated with multiple cerebral and vertebral cavernous malformations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25086949", "endSection": "title" }, { "offsetInBeginSection": 209, "offsetInEndSection": 490, "text": "These genes encode for the proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations 1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3 (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell death 10 (CCM3/PDCD10).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24287896", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 985, "text": "CCM1 is caused by a mutation in the KRIT1 gene and CCM2 is caused by a mutation in the MGC4607 gene, while the gene for CCM3 is not yet identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16100539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12172908", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 712, "text": "At least 45% of families affected with cerebral cavernous malformations harbour a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1, CCM1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14697511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12140362", "endSection": "title" } ] }, { "body": "Is DITPA a thyroid hormone analog utilized in experimental and clinical studies", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "http://www.ncbi.nlm.nih.gov/pubmed/22993035", "http://www.ncbi.nlm.nih.gov/pubmed/10749704", "http://www.ncbi.nlm.nih.gov/pubmed/15072976", "http://www.ncbi.nlm.nih.gov/pubmed/17612639", "http://www.ncbi.nlm.nih.gov/pubmed/9618233", "http://www.ncbi.nlm.nih.gov/pubmed/12414442", "http://www.ncbi.nlm.nih.gov/pubmed/11040100", "http://www.ncbi.nlm.nih.gov/pubmed/9069582", "http://www.ncbi.nlm.nih.gov/pubmed/17710084", "http://www.ncbi.nlm.nih.gov/pubmed/18353884", "http://www.ncbi.nlm.nih.gov/pubmed/8353891", "http://www.ncbi.nlm.nih.gov/pubmed/16616210", "http://www.ncbi.nlm.nih.gov/pubmed/8936682", "http://www.ncbi.nlm.nih.gov/pubmed/21131480", "http://www.ncbi.nlm.nih.gov/pubmed/10329215", "http://www.ncbi.nlm.nih.gov/pubmed/21658725", "http://www.ncbi.nlm.nih.gov/pubmed/19286941", "http://www.ncbi.nlm.nih.gov/pubmed/21215270", "http://www.ncbi.nlm.nih.gov/pubmed/18030062", "http://www.ncbi.nlm.nih.gov/pubmed/10710355", "http://www.ncbi.nlm.nih.gov/pubmed/20080837", "http://www.ncbi.nlm.nih.gov/pubmed/1403782", "http://www.ncbi.nlm.nih.gov/pubmed/19903697", "http://www.ncbi.nlm.nih.gov/pubmed/12145478", "http://www.ncbi.nlm.nih.gov/pubmed/15454853", "http://www.ncbi.nlm.nih.gov/pubmed/10474790", "http://www.ncbi.nlm.nih.gov/pubmed/12165118", "http://www.ncbi.nlm.nih.gov/pubmed/15148346", "http://www.ncbi.nlm.nih.gov/pubmed/19506112", "http://www.ncbi.nlm.nih.gov/pubmed/15572044", "http://www.ncbi.nlm.nih.gov/pubmed/20192904", "http://www.ncbi.nlm.nih.gov/pubmed/16384862", "http://www.ncbi.nlm.nih.gov/pubmed/7828308" ], "ideal_answer": [ "There is very large body of evidence that DITPA is a true thyroid hormone analog, largely utilized in experimental and clinical studies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013956", "http://www.biosemantics.org/jochem#4021241", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ], "type": "yesno", "id": "52fb4b462059c6d71c00005f", "snippets": [ { "offsetInBeginSection": 1036, "offsetInEndSection": 1174, "text": "DITPA normalized the elevated serum T(3) and TSH when the dose reached 1 mg/kg \u00b7 d and T(4) and rT(3) increased to the lower normal range.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22993035", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1067, "text": "The identification of 3,5-diiodothyropropionic acid (DITPA) that binds to both \u03b1- and \u03b2-type TRs with relatively low affinity was unique in that this analog improves left ventricular function in heart failure as well as lowers cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21215270", "endSection": "abstract" }, { "offsetInBeginSection": 1837, "offsetInEndSection": 1937, "text": "Treatment with DITPA attenuates the acute inflammatory response and reduces myocardial infarct size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21658725", "endSection": "abstract" }, { "offsetInBeginSection": 1790, "offsetInEndSection": 1913, "text": "Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21131480", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1443, "text": "DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19506112", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1593, "text": "The results suggested that DITPA can promote a healthy vasculature independently from its thyroid-related metabolic effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19286941", "endSection": "abstract" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1693, "text": " Moreover, DITPA and T(4) were efficacious in preventing effects of hypothyroidism on cardiac function and BVD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18353884", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1349, "text": "Both T4 and DITPA had beneficial effects on chamber remodeling, which was most likely due to beneficial changes in cell shape and improved vascular supply.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17612639", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1539, "text": "The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15454853", "endSection": "abstract" } ] }, { "body": "What is Tarlov Cyst?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20712856", "http://www.ncbi.nlm.nih.gov/pubmed/23400656", "http://www.ncbi.nlm.nih.gov/pubmed/21139800", "http://www.ncbi.nlm.nih.gov/pubmed/25191117", "http://www.ncbi.nlm.nih.gov/pubmed/19110185", "http://www.ncbi.nlm.nih.gov/pubmed/11453427", "http://www.ncbi.nlm.nih.gov/pubmed/21830055", "http://www.ncbi.nlm.nih.gov/pubmed/25216402", "http://www.ncbi.nlm.nih.gov/pubmed/20102100", "http://www.ncbi.nlm.nih.gov/pubmed/19569467", "http://www.ncbi.nlm.nih.gov/pubmed/10758434" ], "ideal_answer": [ "Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral spine level arising between covering layers of the perineurium and the endoneurium near the dorsal root ganglion and are usually asymptomatic." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052958" ], "type": "summary", "id": "56c1d848ef6e39474100002f", "snippets": [ { "offsetInBeginSection": 753, "offsetInEndSection": 975, "text": "She underwent ultrasound, CT, and eventually MRI evaluations that led to the diagnosis of a giant (6.7 \u00d7 6.4 \u00d7 6.6 cm) Tarlov cyst originating from the right S-2 nerve root sleeve/sacral foramen with intrapelvic extension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216402", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 261, "text": "We report here a case of multiloculated disseminated perineural or Tarlov cysts (TCs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191117", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 941, "text": "TCs are typically benign, asymptomatic lesions that can simply be monitored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Tarlov cyst syndrome is a rare, often asymptomatic disorder, characterised by isolated or multiple nerve-root cysts, usually occurring in the sacral spine, near the dorsal root ganglion, between the perineurium and endoneurium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Perineural (Tarlov) cysts are most often found in the sacral region and are rare in the cervical spine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21830055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A case of symptomatic cervical perineural (Tarlov) cyst: clinical manifestation and management.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21830055", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Tarlov cysts or spinal perineurial cysts are uncommon lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19569467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Tarlov cyst syndrome is a rare, often asymptomatic disorder, characterised by isolated or multiple nerve-root cysts, usually occurring in the sacral spine, near the dorsal root ganglion, between the perineurium and endoneurium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Symptomatic sacral perineurial (Tarlov) cysts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20102100", "endSection": "title" }, { "offsetInBeginSection": 668, "offsetInEndSection": 824, "text": "Subsequent MRI and CT myelography demonstrated the nature of the photopenic area as secondary to vertebral erosion by sacral perineurial cyst (Tarlov cyst).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10758434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Tarlov cysts are sacral perineural cysts. This case report describes the clinical course after biopsy of a very large Tarlov cyst via laparoscopy, which was thought preoperatively to be an adnexal mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19110185", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 673, "text": "Subsequent MRI and CT myelography demonstrated the nature of the photopenic area as secondary to vertebral erosion by sacral perineurial cyst (Tarlov cyst).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10758434", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 563, "text": "A spinal MRI scan was then performed and revealed a sacral fracture which drained into an unknown perineurial cyst (Tarlov cyst).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20712856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Tarlov or perineurial cysts are lesions of the nerve root most often found in the sacral region. Although there is agreement that asymptomatic Tarlov cysts should be followed, it is still debated whether patients with symptomatic Tarlov cysts should be treated surgically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11453427", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 287, "text": "Tarlov cysts (sacral perineural cysts) are nerve root cysts found most commonly in the sacral roots,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21139800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Tarlov cysts or spinal perineurial cysts are uncommon lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19569467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Sacral perineurial (Tarlov) cysts are rare lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20102100", "endSection": "abstract" } ] }, { "body": "What are 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin'?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "http://www.ncbi.nlm.nih.gov/pubmed/24793580", "http://www.ncbi.nlm.nih.gov/pubmed/21320267", "http://www.ncbi.nlm.nih.gov/pubmed/24320733", "http://www.ncbi.nlm.nih.gov/pubmed/22215383", "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "http://www.ncbi.nlm.nih.gov/pubmed/22162539", "http://www.ncbi.nlm.nih.gov/pubmed/23803146", "http://www.ncbi.nlm.nih.gov/pubmed/20690781", "http://www.ncbi.nlm.nih.gov/pubmed/19791828", "http://www.ncbi.nlm.nih.gov/pubmed/23837679", "http://www.ncbi.nlm.nih.gov/pubmed/23743694", "http://www.ncbi.nlm.nih.gov/pubmed/23501107", "http://www.ncbi.nlm.nih.gov/pubmed/24996141", "http://www.ncbi.nlm.nih.gov/pubmed/24186878", "http://www.ncbi.nlm.nih.gov/pubmed/21500969", "http://www.ncbi.nlm.nih.gov/pubmed/24793219", "http://www.ncbi.nlm.nih.gov/pubmed/22686547", "http://www.ncbi.nlm.nih.gov/pubmed/22106978", "http://www.ncbi.nlm.nih.gov/pubmed/21913883", "http://www.ncbi.nlm.nih.gov/pubmed/25687897", "http://www.ncbi.nlm.nih.gov/pubmed/25860270", "http://www.ncbi.nlm.nih.gov/pubmed/17100408", "http://www.ncbi.nlm.nih.gov/pubmed/23136353", "http://www.ncbi.nlm.nih.gov/pubmed/24567800", "http://www.ncbi.nlm.nih.gov/pubmed/22429011", "http://www.ncbi.nlm.nih.gov/pubmed/18223196" ], "ideal_answer": [ "\"Sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and \"dutogliptin\" are dipeptidyl peptidase-4 (DPP-4) inhibitors." ], "exact_answer": [ "dipeptidyl peptidase-4 (DPP-4) inhibitors" ], "concepts": [ "http://www.biosemantics.org/jochem#4243818", "http://www.biosemantics.org/jochem#4243458", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054873", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018819", "http://www.biosemantics.org/jochem#4274679", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069476", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4274679" ], "type": "factoid", "id": "571e275dbb137a4b0c000005", "snippets": [ { "offsetInBeginSection": 301, "offsetInEndSection": 785, "text": "The present metaanalysis was designed to assess the effect of DPP-4 inhibitors on blood lipids, verifying possible differences across compounds of this class.METHODS: An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words \"sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and/or \"dutogliptin.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22215383", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 600, "text": "Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1217, "text": "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Testing the therapeutic equivalence of alogliptin, linagliptin, saxagliptin, sitagliptin or vildagliptin as monotherapy or in combination with metformin in patients with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793219", "endSection": "title" }, { "offsetInBeginSection": 442, "offsetInEndSection": 732, "text": "The aim of this review is to compare the clinical pharmacokinetics of available DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin) for the purpose of identifying potential selection preferences according to individual patient variables and co-morbidities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22686547", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 594, "text": "The reader will gain detailed pharmacological and clinical information on alogliptin, dutogliptin and linagliptin and will learn how these DPP IV inhibitors may widen the whole drug class.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21500969", "endSection": "abstract" }, { "offsetInBeginSection": 3646, "offsetInEndSection": 3955, "text": "When considered in total, data reviewed in this report suggest that the best overall balance between potency and the clinical pharmacokinetic characteristics of distribution, metabolism and elimination may be observed with linagliptin followed closely by vildagliptin, saxagliptin, sitagliptin and alogliptin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22686547", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 854, "text": "Currently, there are four DPP IV inhibitors available in various countries-alogliptin, sitagliptin, vildagliptin and saxagliptin (1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 464, "text": "The various marketed or under developmental status, potential gliptins have been opted to build a pharmacophore model, e.g. Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 723, "text": "Currently, there are four DPP IV inhibitors available in various countries-alogliptin, sitagliptin, vildagliptin and saxagliptin (1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 1023, "text": "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Recently, the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus--Thrombolysis in Myocardial Infarction-53) reported a significant increase in the risk of hospitalizations for heart failure in patients treated with saxagliptin in comparison with placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793580", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 824, "text": "Of these, two have been approved for clinical use in the United States: sitagliptin and saxagliptin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24186878", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "To investigate the long-term safety and efficacy of empagliflozin, a sodium glucose cotransporter 2 inhibitor; sitagliptin; and metformin in patients with type 2 diabetes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24186878", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 543, "text": "METHODS: DATA SOURCES: an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23837679", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 574, "text": "RESEARCH DESIGN AND METHODS: An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22106978", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 632, "text": "METHODS: We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy in patients with T2DM by the end of December 2012, using the key words 'alogliptin', 'dutogliptin', 'linagliptin', 'saxagliptin', 'sitagliptin', 'vildagliptin' and 'metformin'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23803146", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 466, "text": "Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 780, "text": "Aim of the present meta-analysis is the systematic collection and synthesis of information on treatment-emergent cases of acute heart failure described in randomized clinical trials with DPP4.DATA SOURCES: An extensive Medline, Embase, and Cochrane Database search for \"vildagliptin\", \"sitagliptin\", \"saxagliptin\", \"alogliptin\", \"linagliptin\", and \"dutogliptin\" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Quantitative model of the relationship between dipeptidyl peptidase-4 (DPP-4) inhibition and response: meta-analysis of alogliptin, saxagliptin, sitagliptin, and vildagliptin efficacy results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22162539", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The dipeptidyl peptidase-4 (DPP-4) inhibitors linagliptin, sitagliptin, saxagliptin, vildagliptin and alogliptin are being developed and have been approved for the treatment of type-2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913883", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 313, "text": "The objective of this model-based meta-analysis was to describe the time course of HbA1c response after dosing with alogliptin (ALOG), saxagliptin (SAXA), sitagliptin (SITA), or vildagliptin (VILD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22162539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Discovery of highly potent DPP-4 inhibitors by hybrid compound design based on linagliptin and alogliptin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24996141", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320733", "endSection": "title" }, { "offsetInBeginSection": 1399, "offsetInEndSection": 1627, "text": "In conclusion, BI 1356 inhibited DPP-4 more effectively than vildagliptin, sitagliptin, saxagliptin, and alogliptin and has the potential to become the first truly once-a-day DPP-4 inhibitor for the treatment of type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18223196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Highly potent DPP-4 inhibitors have been identified by hybrid compound design based on linagliptin and alogliptin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24996141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "AIM: We assessed the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin, sitagliptin, saxagliptin and alogliptin to reach the haemoglobin HbA1c target of <7% in people with type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21320267", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 337, "text": "Whether the DPP-IV inhibitors sitagliptin, vildagliptin or saxagliptin impair immune responses is, however, currently unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320733", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 278, "text": "OBJECTIVE: To assess the efficacy and safety of DPP-4 inhibitors, including sitagliptin, saxagliptin, vildagliptin, and linagliptin, in type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23136353", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1042, "text": "Given as monotherapy, linagliptin, sitagliptin, and vildagliptin (but not saxagliptin) met the equivalence criterion when compared with one another.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793219", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1225, "text": "Given in combination with metformin, linagliptin, saxagliptin, sitagliptin, and vildagliptin showed an equivalent effect whereas alogliptin did not satisfy the equivalence criterion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793219", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 514, "text": "an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23837679", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 533, "text": "An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22106978", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 748, "text": "An extensive Medline, Embase, and Cochrane Database search for \"vildagliptin\", \"sitagliptin\", \"saxagliptin\", \"alogliptin\", \"linagliptin\", and \"dutogliptin\" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 12, "text": "Saxagliptin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19791828", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 13, "text": "Vildagliptin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17100408", "endSection": "title" }, { "offsetInBeginSection": 327, "offsetInEndSection": 515, "text": "an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23837679", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 534, "text": "An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22106978", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 749, "text": "An extensive Medline, Embase, and Cochrane Database search for \"vildagliptin\", \"sitagliptin\", \"saxagliptin\", \"alogliptin\", \"linagliptin\", and \"dutogliptin\" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793580", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 864, "text": "the words \"sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and/or \"dutogliptin.\" Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22215383", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 466, "text": "Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 1025, "text": "Of these, two have been approved for clinical use in the United States: sitagliptin and saxagliptin. Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 617, "text": "We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy in patients with T2DM by the end of December 2012, using the key words 'alogliptin', 'dutogliptin', 'linagliptin', 'saxagliptin', 'sitagliptin', 'vildagliptin' and 'metformin'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23803146", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1226, "text": "Given as monotherapy, linagliptin, sitagliptin, and vildagliptin (but not saxagliptin) met the equivalence criterion when compared with one another. Given in combination with metformin, linagliptin, saxagliptin, sitagliptin, and vildagliptin showed an equivalent effect whereas alogliptin did not satisfy the equivalence criterion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793219", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1114, "text": "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2). Alogliptin was approved for use in Japan under the trade name Nesina\u00ae in April 2010 (3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 817, "text": "Any DPP-4 inhibitor (vildagliptin, sitagliptin, saxagliptin, linagliptin or alogliptin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687897", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 898, "text": "An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words \"sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and/or \"dutogliptin.\" Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website, using the same keywords as above.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22215383", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 345, "text": "A systematic review and meta-analysis of randomised controlled trials (RCTs) of DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin and alogliptin) on HbA1c were conducted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687897", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 780, "text": "Several clinical trials have studied the addition of GLP-1 receptor agonists [exenatide BID (twice daily), lixisenatide, albiglutide] or DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, alogliptin, linagliptin) to ongoing insulin therapy or adding insulin to ongoing therapy with a GLP-1 receptor agonist (liraglutide).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24567800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Testing the therapeutic equivalence of alogliptin, linagliptin, saxagliptin, sitagliptin or vildagliptin as monotherapy or in combination with metformin in patients with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793219", "endSection": "title" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1025, "text": "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431099", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1326, "text": "This review summarizes the available data on drug-drug interactions reported in the literature for these five DDP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20690781", "endSection": "abstract" } ] }, { "body": "Which is the most important prognosis sub-classification in Chronic Lymphocytic Leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22560084", "http://www.ncbi.nlm.nih.gov/pubmed/16083281", "http://www.ncbi.nlm.nih.gov/pubmed/23468975", "http://www.ncbi.nlm.nih.gov/pubmed/20353875", "http://www.ncbi.nlm.nih.gov/pubmed/16014569", "http://www.ncbi.nlm.nih.gov/pubmed/20090781", "http://www.ncbi.nlm.nih.gov/pubmed/17786276", "http://www.ncbi.nlm.nih.gov/pubmed/19500131", "http://www.ncbi.nlm.nih.gov/pubmed/16825496", "http://www.ncbi.nlm.nih.gov/pubmed/19127482" ], "ideal_answer": [ "The mutational status of the immunoglobulin heavy variable (IGHV) genes, defines two subsets: mutated and unmutated CLL. Unmutated CLL patients show a shorter progression-free and overall survival than mutated CLL patients." ], "exact_answer": [ "The mutational status of the IGHV genes." ], "type": "factoid", "id": "51739df58ed59a060a00001c", "snippets": [ { "offsetInBeginSection": 621, "offsetInEndSection": 879, "text": "One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22560084", "endSection": "sections.0" }, { "offsetInBeginSection": 119, "offsetInEndSection": 268, "text": "Mutational status of the immunoglobulin heavy chain variable regions (IGHVs) of CLL cells offers useful prognostic information for high-risk patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20090781", "endSection": "sections.0" }, { "offsetInBeginSection": 270, "offsetInEndSection": 496, "text": "but time and economical costs originally prevented it from being routinely used in a clinical setting. Instead, alternative markers of IGHV status, such as zeta-associated protein (ZAP70) or messenger RNA levels are often used", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20090781", "endSection": "sections.0" }, { "offsetInBeginSection": 109, "offsetInEndSection": 282, "text": "Patients with unmutated IgV(H) gene show a shorter progression-free and overall survival than patients with immunoglobulin heavy chain variable regions (IgV(H)) gene mutated", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19127482", "endSection": "sections.0" } ] }, { "body": "Is MammaPrint cleared by the United States Food and Drug Administration? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19506735", "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "http://www.ncbi.nlm.nih.gov/pubmed/18786252" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17680439", "o": "MammaPrint" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2827401", "o": "http://linkedlifedata.com/resource/umls/label/A17680439" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F383737393600D", "o": "fda" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4530503539300011", "o": "fda" } ], "ideal_answer": [ "Yes. MammaPrint is cleared by the FDA for breast cancer recurrence." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017322", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017327", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017326" ], "type": "yesno", "id": "5168023b298dcd4e51000061", "snippets": [ { "offsetInBeginSection": 1350, "offsetInEndSection": 1539, "text": "Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "endSection": "sections.0" } ] }, { "body": "Is amantadine effective for treatment of disorders conciousness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15759228", "http://www.ncbi.nlm.nih.gov/pubmed/19894299", "http://www.ncbi.nlm.nih.gov/pubmed/20129511", "http://www.ncbi.nlm.nih.gov/pubmed/18540467", "http://www.ncbi.nlm.nih.gov/pubmed/20658796", "http://www.ncbi.nlm.nih.gov/pubmed/22375973", "http://www.ncbi.nlm.nih.gov/pubmed/20460949", "http://www.ncbi.nlm.nih.gov/pubmed/24025054", "http://www.ncbi.nlm.nih.gov/pubmed/24025057", "http://www.ncbi.nlm.nih.gov/pubmed/24025056", "http://www.ncbi.nlm.nih.gov/pubmed/19404190", "http://www.ncbi.nlm.nih.gov/pubmed/15825541" ], "ideal_answer": [ "Amantadine, a dopaminergic agent, has been shown to be effective for induction of recovery from disorders of consciousness. Amantadine is a commonly prescribed medication for patients with prolonged disorders of consciousness after traumatic brain injury. Amantadine accelerates the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. Higher dosing of amantadine may be considered in the setting of brain injury." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4095490", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000547", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.biosemantics.org/jochem#4278064", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003244" ], "type": "yesno", "id": "530f7cdde3eabad021000001", "snippets": [ { "offsetInBeginSection": 266, "offsetInEndSection": 599, "text": "We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025057", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1368, "text": "Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic medications desipramine, amitriptyline, protriptyline and fluoxetine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025056", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1162, "text": "Sporadic cases of recovery from a DOC have been reported after the administration of various pharmacological agents (baclofen, zolpidem, amantadine etc.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025054", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 256, "text": "Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22375973", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1143, "text": " During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22375973", "endSection": "abstract" }, { "offsetInBeginSection": 1748, "offsetInEndSection": 1886, "text": "Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22375973", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1718, "text": "Sporadic cases of dramatic recovery from DOC after the administration of various pharmacological agents, such as baclofen, zolpidem and amantadine, have been recently supported by intriguing scientific observations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20658796", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1149, "text": "According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20460949", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1307, "text": "Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129511", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1569, "text": "Based on the preliminary data, higher dosing may be considered in the setting of brain injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129511", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 1046, "text": "Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19894299", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1068, "text": "There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404190", "endSection": "abstract" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1276, "text": "This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404190", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 332, "text": "The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18540467", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 926, "text": "This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15825541", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1704, "text": "Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15759228", "endSection": "abstract" } ] }, { "body": "What is needed for MMP proteins to be functional?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25360794", "http://www.ncbi.nlm.nih.gov/pubmed/24570026", "http://www.ncbi.nlm.nih.gov/pubmed/26013370", "http://www.ncbi.nlm.nih.gov/pubmed/23001203", "http://www.ncbi.nlm.nih.gov/pubmed/26087627", "http://www.ncbi.nlm.nih.gov/pubmed/26150355", "http://www.ncbi.nlm.nih.gov/pubmed/22257051" ], "ideal_answer": [ "Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases." ], "exact_answer": [ "zinc" ], "type": "factoid", "id": "56e857ae42442bac75000004", "snippets": [ { "offsetInBeginSection": 73, "offsetInEndSection": 105, "text": "matrix metalloproteinase (MMP)-9", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26013370", "endSection": "abstract" }, { "offsetInBeginSection": 57, "offsetInEndSection": 97, "text": "matrix metalloproteinase-3 (MMP-3) gene ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087627", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 710, "text": "matrix metalloproteinases (MMPs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24570026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Matrix metalloproteinase-9 (MMP-9) is a secreted glycoprotein with a major role in shaping the extracellular matrix and a detailed understanding of the secretory mechanism could help identify methods to correct diseases resulting from dysregulation of secretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26150355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Gelatinase B/matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) cleaves many substrates and is produced by most cell types\u00a0as a zymogen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25360794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases involved in physiological and pathological processes, through the cleavage of extracellular matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22257051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Extracellular matrix metalloproteinases (MMPs) are a family of endopeptydases which recquire a zinc ion at their active site, for proteolityc activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001203", "endSection": "abstract" } ] }, { "body": "What is hyperosmia", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24302690", "http://www.ncbi.nlm.nih.gov/pubmed/21250223", "http://www.ncbi.nlm.nih.gov/pubmed/23520356" ], "ideal_answer": [ "Hyperosmia is increased olfactory acuity ", "increased olfactory acuity" ], "exact_answer": [ "increased olfactory acuity" ], "type": "factoid", "id": "5509c52f1180f13250000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Hyperosmia is suspected in pregnancy; however, no empirical study using validated measures of olfactory function has clearly confirmed the anecdotal reports of this phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24302690", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 676, "text": "subjective hyperosmia is associated with primarily negative odor-related experiences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23520356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Hyperosmia is increased olfactory acuity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21250223", "endSection": "abstract" } ] }, { "body": "What is the number of long non coding RNAs in the human genome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23126680", "http://www.ncbi.nlm.nih.gov/pubmed/23846593", "http://www.ncbi.nlm.nih.gov/pubmed/23369519" ], "ideal_answer": [ "Different estimates put currently the number of human long non coding RNAs between 10,000 and 20,000" ], "exact_answer": [ "between 10,000 and 20,000" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085" ], "type": "factoid", "id": "535d2cf09a4572de6f000004", "snippets": [ { "offsetInBeginSection": 344, "offsetInEndSection": 516, "text": "The recent ENCODE (Encyclopedia of DNA Elements) study reported 9,640 lncRNA loci in the human genome, which corresponds to around half the number of protein-coding genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23126680", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 695, "text": "Over 18,000 transcripts are presently annotated as lncRNA, and encompass previously annotated classes of noncoding transcripts including large intergenic noncoding RNA, antisense RNA and processed pseudogenes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23846593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "BACKGROUND: Over 10,000 long intergenic non-coding RNAs (lincRNAs) have been identified in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23369519", "endSection": "abstract" } ] }, { "body": "Which is the most known bacterium responsible for botulism (sausage-poisoning)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24961027", "http://www.ncbi.nlm.nih.gov/pubmed/24246230", "http://www.ncbi.nlm.nih.gov/pubmed/24206405", "http://www.ncbi.nlm.nih.gov/pubmed/24252222", "http://www.ncbi.nlm.nih.gov/pubmed/23025151", "http://www.ncbi.nlm.nih.gov/pubmed/19573697", "http://www.ncbi.nlm.nih.gov/pubmed/17458494", "http://www.ncbi.nlm.nih.gov/pubmed/20569065", "http://www.ncbi.nlm.nih.gov/pubmed/23421373", "http://www.ncbi.nlm.nih.gov/pubmed/21975066", "http://www.ncbi.nlm.nih.gov/pubmed/21130733", "http://www.ncbi.nlm.nih.gov/pubmed/15027048", "http://www.ncbi.nlm.nih.gov/pubmed/18388640", "http://www.ncbi.nlm.nih.gov/pubmed/16080379", "http://www.ncbi.nlm.nih.gov/pubmed/23971808", "http://www.ncbi.nlm.nih.gov/pubmed/23523511", "http://www.ncbi.nlm.nih.gov/pubmed/23971806", "http://www.ncbi.nlm.nih.gov/pubmed/23971804", "http://www.ncbi.nlm.nih.gov/pubmed/24253240", "http://www.ncbi.nlm.nih.gov/pubmed/24252701", "http://www.ncbi.nlm.nih.gov/pubmed/15839401", "http://www.ncbi.nlm.nih.gov/pubmed/11153358", "http://www.ncbi.nlm.nih.gov/pubmed/21747146", "http://www.ncbi.nlm.nih.gov/pubmed/24997242", "http://www.ncbi.nlm.nih.gov/pubmed/21171846", "http://www.ncbi.nlm.nih.gov/pubmed/20961439", "http://www.ncbi.nlm.nih.gov/pubmed/23239346" ], "ideal_answer": [ "Botulism is a severe neuroparalytic disease caused by botulinum neurotoxin (BoNT), and affects humans, all warm-blooded animals, birds, and some fishes. Botulinum toxin is produced under anaerobic conditions by the bacterium Clostridium botulinum, which is the most known etiological agent of the disease, and some other clostridia, and is one of the most dangerous toxin in the world." ], "exact_answer": [ "Clostridium botulinum" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11976" ], "type": "factoid", "id": "55475dc2f35db75526000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24253240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Cattle botulism is a fatal intoxication caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Botulism in horses in the USA is attributed to Clostridium botulinum types A, B or C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Clostridium botulinum is the etiological agent of botulism. Due to food-borne poisoning and the potential use of the extremely toxic botulinum neurotoxin (BoNT) from C. botulinum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246230", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 207, "text": "Botulism is a serious neuroparalytic disease caused by toxins of Clostridium botulinum. Botulinum toxin is produced under anaerobic conditions and is one of the most dangerous toxin in the world.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24206405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Botulism is a neuroparalytic disease that can occur in all warm-blooded animals, birds, and fishes. The disease in animals is mainly caused by toxins produced by Clostridium botulinum strains belonging to group III, although outbreaks due to toxins produced by group I and II organisms have been recognized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23971808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Botulism is a severe neuroparalytic disease that affects humans, all warm-blooded animals, and some fishes. The disease is caused by exposure to toxins produced by Clostridium botulinum and other botulinum toxin-producing clostridia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23971806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "The botulinum neurotoxins (BoNTs) produced by different strains of the bacterium Clostridium botulinum are responsible for the disease botulism and include a group of immunologically distinct serotypes (A, B, E, and F) that are considered to be the most lethal natural proteins known for humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21130733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Botulinumtoxin (BTX) is a neurotoxin produced from Clostridium botulinum under anaerobic conditions and is responsible for botulism, a notifiable, bacterial form of food poisoning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Botulism is a disease characterized by neuromuscular paralysis and is produced from botulinum neurotoxins (BoNTs) found within the Gram positive bacterium Clostridium botulinum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21975066", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 248, "text": "An epidemiological investigation and laboratory detection studies showed that sausage contaminated by type A Clostridium botulinum caused this outbreak of food poisoning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20569065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Botulism is caused by botulinum neurotoxin produced by the bacterium Clostridium botulinum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23025151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Botulinumtoxin (BTX) is a neurotoxin produced from Clostridium botulinum under anaerobic conditions and is responsible for botulism, a notifiable, bacterial form of food poisoning", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153358", "endSection": "abstract" } ] }, { "body": "What is the association of spermidine with \u03b1-synuclein neurotoxicity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25483063", "http://www.ncbi.nlm.nih.gov/pubmed/22662273" ], "ideal_answer": [ "Spermidine protects against \u03b1-synuclein neurotoxicity. In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human \u03b1-synuclein, which is thought to be the principal toxic trigger of Parkinson's Disease (PD). In this line, administration of spermidine rescued \u03b1-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes. Alleviation of PD-related neurodegeneration by spermidine was accompanied by induction of autophagy, suggesting that this cytoprotective process may be responsible for the beneficial effects of spermidine administration." ], "exact_answer": [ "Spermidine protects against \u03b1-synuclein neurotoxicity" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013095", "http://www.biosemantics.org/jochem#4275085", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275085" ], "type": "factoid", "id": "56c073fcef6e394741000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Spermidine protects against \u03b1-synuclein neurotoxicity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483063", "endSection": "title" }, { "offsetInBeginSection": 227, "offsetInEndSection": 1132, "text": "Here, we show that administration of the naturally occurring polyamine spermidine, which declines continuously during aging in various species, alleviates a series of PD-related degenerative processes in the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, two established model systems for PD pathology. In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human \u03b1-synuclein, which is thought to be the principal toxic trigger of PD. In this line, administration of spermidine rescued \u03b1-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes. Alleviation of PD-related neurodegeneration by spermidine was accompanied by induction of autophagy, suggesting that this cytoprotective process may be responsible for the beneficial effects of spermidine administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483063", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Spermidine protects against \u03b1-synuclein neurotoxicity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483063", "endSection": "title" }, { "offsetInBeginSection": 558, "offsetInEndSection": 910, "text": "In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human \u03b1-synuclein, which is thought to be the principal toxic trigger of PD. In this line, administration of spermidine rescued \u03b1-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483063", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1483, "text": "Together with the fact that spermidine facilitates late stages of \u03b1-Syn aggregation, our data demonstrate that spermidine promotes the very early stages of protein aggregation including \u03b1-Syn misfolding and dimerization. This finding suggests that increased levels of spermidine and potentially other polyamines can initiate the disease-related process of \u03b1-Syn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22662273", "endSection": "abstract" } ] }, { "body": "List symptoms of 4H leukodystrophy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24190003", "http://www.ncbi.nlm.nih.gov/pubmed/18671210", "http://www.ncbi.nlm.nih.gov/pubmed/23307887", "http://www.ncbi.nlm.nih.gov/pubmed/23242285", "http://www.ncbi.nlm.nih.gov/pubmed/22855961", "http://www.ncbi.nlm.nih.gov/pubmed/21855841", "http://www.ncbi.nlm.nih.gov/pubmed/22451160", "http://www.ncbi.nlm.nih.gov/pubmed/25339210" ], "ideal_answer": [ "Hypomyelination, hypodontia, and hypogonadotropic hypogonadism are major symptoms of 4H leukodystrophy." ], "exact_answer": [ [ "hypomyelination" ], [ "hypodontia" ], [ "hypogonadotropic hypogonadism" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10579" ], "type": "list", "id": "550320cbe9bde6963400002d", "snippets": [ { "offsetInBeginSection": 161, "offsetInEndSection": 426, "text": " MRI demonstrated diffuse cerebral hypomyelination, cerebellar atrophy, and thin corpus callosum; X-ray revealed persistent milk teeth and hypoplastic crowns and roots (figure), indicative of 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24190003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "4H syndrome is a rare and distinct leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23307887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242285", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 887, "text": " The five overlapping clinical phenotypes (described as distinct entities before their molecular basis was known) include: Hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); Ataxia, delayed dentition, and hypomyelination (ADDH); Tremor-ataxia with central hypomyelination (TACH); Leukodystrophy with oligodontia (LO); and Hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22855961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "OBJECTIVE: To report a novel clinical and genetic presentation of a patient with 4H syndrome, which is a recently described leukodystrophy syndrome characterized by ataxia, hypomyelination, hypodontia, and hypogonadotropic hypogonadism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451160", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 905, "text": "Because these families were mapped to the same locus as leukodystrophy with oligodontia (LO) and presented clinical and radiological overlap with individuals with hypomyelination, hypodontia and hypogonadotropic hypogonadism (4H) syndrome, we sequenced this gene in nine individuals with 4H and eight with LO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21855841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "AIM: To report one patient with slowly progressive encephalopathy, ataxia, central hypomyelination, hypodontia and hypogonadotropic hypogonadism, the 4H syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18671210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "4H syndrome is a rare and distinct leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23307887", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 903, "text": "Because these families were mapped to the same locus as leukodystrophy with oligodontia (LO) and presented clinical and radiological overlap with individuals with hypomyelination, hypodontia and hypogonadotropic hypogonadism (4H) syndrome, we sequenced this gene in nine individuals with 4H and eight with LO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21855841", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 424, "text": "MRI demonstrated diffuse cerebral hypomyelination, cerebellar atrophy, and thin corpus callosum; X-ray revealed persistent milk teeth and hypoplastic crowns and roots (figure), indicative of 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24190003", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 904, "text": "Because these families were mapped to the same locus as leukodystrophy with oligodontia (LO) and presented clinical and radiological overlap with individuals with hypomyelination, hypodontia and hypogonadotropic hypogonadism (4H) syndrome, we sequenced this gene in nine individuals with 4H and eight with LO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21855841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "4H syndrome is a rare and distinct leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23307887", "endSection": "abstract" } ] }, { "body": "What is the extracellular core \"matrisome\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23539364", "http://www.ncbi.nlm.nih.gov/pubmed/22159717", "http://www.ncbi.nlm.nih.gov/pubmed/21937732" ], "ideal_answer": [ "The \"matrisome\" is defined as the ensemble of extracellular matrix proteins (ECM) proteins and associated factors. The core matrisome have been defined in mammals through the analysis of whole genome sequences and comprises of ~ 300 proteins." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031012", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005576", "http://www.uniprot.org/uniprot/MATRX_BRSVA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005109" ], "type": "summary", "id": "53312464d6d3ac6a3400003a", "snippets": [ { "offsetInBeginSection": 152, "offsetInEndSection": 287, "text": "Over 300 ECM molecules have been defined as comprising the \"core matrisome\" in mammals through the analysis of whole genome sequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Completion of genome sequences for many organisms allows a reasonably complete definition of the complement of extracellular matrix (ECM) proteins. In mammals this \"core matrisome\" comprises \u223c300 proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21937732", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 600, "text": "we have developed a bioinformatic approach to predict the in silico \"matrisome\" defined as the ensemble of ECM proteins and associated factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22159717", "endSection": "abstract" } ] }, { "body": "Is GAGA associated with nucleosome-free regions (NFR)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15579691", "http://www.ncbi.nlm.nih.gov/pubmed/8474442", "http://www.ncbi.nlm.nih.gov/pubmed/11158316", "http://www.ncbi.nlm.nih.gov/pubmed/7737124" ], "ideal_answer": [ "The GAGA factor is a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin. The interactions of GAGA factor and heat shock factor with their binding sites in chromatin occurred in two modes. Their interaction with binding sites in the nucleosome-free regions did not require ATP. In the presence of ATP both factors interacted also with nucleosomal binding sites, causing nucleosome rearrangements and a refinement of nucleosome positions. While chromatin remodeling upon transcription factor interaction has previously been interpreted to involve nucleosome disruption, the data suggest energy-dependent nucleosome sliding as main principle of chromatin reorganization.", "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. To study the contribution of transcription factors to the establishment of this specific chromatin configuration we assembled nucleosomes on the hsp26 promoter using a cell-free reconstitution system derived from fly embryos. This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) sites (Q. Lu, L.L. Wallrath, B.D. Allan, R.L. Glaser, J.T. Lis, and S.C.R. Elgin, J. Mol. Biol. Both DH sites were readily reconstituted from extract components.", "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016584", "http://amigo.geneontology.org/amigo/term/GO:0034728", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009707", "http://amigo.geneontology.org/amigo/term/GO:0000786" ], "type": "yesno", "id": "56f3f6b12ac5ed145900001a", "snippets": [ { "offsetInBeginSection": 261, "offsetInEndSection": 510, "text": "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15579691", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 832, "text": "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11158316", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 980, "text": "The interactions of GAGA factor and heat shock factor with their binding sites in chromatin occurred in two modes. Their interaction with binding sites in the nucleosome-free regions did not require ATP. In the presence of ATP both factors interacted also with nucleosomal binding sites, causing nucleosome rearrangements and a refinement of nucleosome positions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7737124", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1212, "text": "While chromatin remodeling upon transcription factor interaction has previously been interpreted to involve nucleosome disruption, the data suggest energy-dependent nucleosome sliding as main principle of chromatin reorganization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7737124", "endSection": "abstract" }, { "offsetInBeginSection": 1795, "offsetInEndSection": 1942, "text": " These (CT)n repeats are associated with a nonhistone protein(s) in vivo and are bound by a purified Drosophila protein, the GAGA factor, in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8474442", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 630, "text": "This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) site", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8474442", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1086, "text": "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11158316", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 758, "text": "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15579691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "The iab-7 polycomb response element maps to a nucleosome-free region of chromatin and requires both GAGA and pleiohomeotic for silencing activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11158316", "endSection": "title" }, { "offsetInBeginSection": 574, "offsetInEndSection": 833, "text": "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11158316", "endSection": "abstract" } ] }, { "body": "Which are the plant DNA (cytosine-5) methyltransferase families?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11353082", "http://www.ncbi.nlm.nih.gov/pubmed/18640997", "http://www.ncbi.nlm.nih.gov/pubmed/21060858", "http://www.ncbi.nlm.nih.gov/pubmed/10845458", "http://www.ncbi.nlm.nih.gov/pubmed/8152926", "http://www.ncbi.nlm.nih.gov/pubmed/21542302", "http://www.ncbi.nlm.nih.gov/pubmed/9680985", "http://www.ncbi.nlm.nih.gov/pubmed/10781108", "http://www.ncbi.nlm.nih.gov/pubmed/8389441", "http://www.ncbi.nlm.nih.gov/pubmed/17689048", "http://www.ncbi.nlm.nih.gov/pubmed/19132393", "http://www.ncbi.nlm.nih.gov/pubmed/20331964" ], "ideal_answer": [ "The plant DNA (cytosine-5)methyltransferases are classified into the families: MET, CMT, and the de novo DRM." ], "exact_answer": [ [ "MET" ], [ "CMT" ], [ "DRM" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248", "http://www.uniprot.org/uniprot/CMT1_DICDI" ], "type": "list", "id": "511a4d391159fa8212000003", "snippets": [ { "offsetInBeginSection": 370, "offsetInEndSection": 760, "text": "The topologies of the trees were overall congruent: four monophyletic groups corresponding to the four plant C5-MTase families were clearly distinguished. In addition, sequence analyses of the plant C5-MTase target recognition domain sequences were performed and phylogenetic trees were reconstructed showing that there is good conservation among but not within the plant C5-MTase families.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17689048", "endSection": "sections.0" }, { "offsetInBeginSection": 399, "offsetInEndSection": 605, "text": "To determine the inheritance of DNA methyltransferase genes and their expression patterns we examined three major DNA methyltransferase families (MET1, CMT3 and DRM) from tobacco and the progenitor species.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19132393", "endSection": "sections.0" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1475, "text": "The comparative investigation of transcription levels of different genes of cytosine DNA methyltransferase family MET (MET1, MET2a, MET2b, MET3) and their methylation patterns shows that there may exist some mechanisms defending the most actively transcribed gene MET1 of this family from methylation mediated silencing. In contrast to DRM2 gene we could not find any adenine methylated GATC sites in the MET1 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542302", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Using the 1kb 3' terminal DNA fragment of the mouse methyltransferase cDNA as a probe and low stringent hybridisation conditions, a new potential methyltransferase (MTase) gene family was isolated from an Arabidopsis thaliana genomic DNA library.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8152926", "endSection": "sections.0" }, { "offsetInBeginSection": 292, "offsetInEndSection": 752, "text": "The Dnmt3 family of de novo DNA methyltransferases has recently been characterized in animals. Here we describe DNA methyltransferase genes from both Arabidopsis and maize that show a high level of sequence similarity to Dnmt3, suggesting that they encode plant de novo methyltransferases. Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10781108", "endSection": "sections.0" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1417, "text": "These results provide the first direct demonstration that DNA-METases of a higher eukaryote are encoded by a gene family.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9680985", "endSection": "sections.0" }, { "offsetInBeginSection": 183, "offsetInEndSection": 312, "text": "Here we show that Arabidopsis DNA methyltransferase2 (AtDNMT2) is localized in nucleus and associates with histone deacetylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20331964", "endSection": "sections.0" }, { "offsetInBeginSection": 344, "offsetInEndSection": 651, "text": "To explore possible relationships between DNA methylation level and accumulation of DNA-(cytosine-5) methyltransferase (DNMT) transcripts, the full-length coding sequences corresponding to three different DNMT families in oil palm, namely the MET, CMT, and DRM classes, have been isolated and characterized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18640997", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "In Arabidopsis a SWI2/SNF2 chromatin remodeling factor-related protein DDM1 and a cytosine methyltransferase MET1 are required for maintenance of genomic cytosine methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11353082", "endSection": "sections.0" }, { "offsetInBeginSection": 582, "offsetInEndSection": 752, "text": "Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10781108", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "In the present study, the isolation and characterization of two distinct cDNAs that code for carrot DNA (cytosine-5)-methyltransferase (DNA-METase) are reported.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9680985", "endSection": "sections.0" }, { "offsetInBeginSection": 709, "offsetInEndSection": 908, "text": "The Arabidopsis methylase has eight of the ten conserved sequence motifs found in prokaryote cytosine-5 methyltransferases and shows 50% homology to the murine enzyme in the methyltransferase domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8389441", "endSection": "sections.0" }, { "offsetInBeginSection": 553, "offsetInEndSection": 674, "text": "As deduced form the DNA sequence this protein contains all conserved sequence motifs specific for the 5m cytosine MTases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8152926", "endSection": "sections.0" } ] }, { "body": "Where is the histone variant CENPA preferentially localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18314594", "http://www.ncbi.nlm.nih.gov/pubmed/23439889", "http://www.ncbi.nlm.nih.gov/pubmed/23562479", "http://www.ncbi.nlm.nih.gov/pubmed/20940262", "http://www.ncbi.nlm.nih.gov/pubmed/12953060", "http://www.ncbi.nlm.nih.gov/pubmed/12906131", "http://www.ncbi.nlm.nih.gov/pubmed/10655499", "http://www.ncbi.nlm.nih.gov/pubmed/12011073", "http://www.ncbi.nlm.nih.gov/pubmed/9465302", "http://www.ncbi.nlm.nih.gov/pubmed/16314512", "http://www.ncbi.nlm.nih.gov/pubmed/18411404", "http://www.ncbi.nlm.nih.gov/pubmed/24213134", "http://www.ncbi.nlm.nih.gov/pubmed/20119530", "http://www.ncbi.nlm.nih.gov/pubmed/19778997", "http://www.ncbi.nlm.nih.gov/pubmed/12217960", "http://www.ncbi.nlm.nih.gov/pubmed/21508988", "http://www.ncbi.nlm.nih.gov/pubmed/9605877", "http://www.ncbi.nlm.nih.gov/pubmed/21888900" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B5XB04", "o": "http://linkedlifedata.com/resource/#_423558423034001A" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_423558423034001A", "o": "CENPA" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4235584230340015", "o": "Histone H3" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B9EMI5", "o": "http://linkedlifedata.com/resource/#_4239454D49350018" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4239454D49350013", "o": "Histone H3" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4239454D49350018", "o": "CENPA" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/C1BY79", "o": "http://linkedlifedata.com/resource/#_4331425937390011" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4331425937390011", "o": "CENPA" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_43314259373900C", "o": "Histone H3" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/A5HUM4", "o": "http://linkedlifedata.com/resource/#_413548554D3400C" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_413548554D3400C", "o": "CenpA" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413548554D34008", "o": "Histone H3" } ], "ideal_answer": [ "Centromere protein A (Cenpa for mouse, CENP-A for other species) is an essential histone H3-like protein that localizes to the centromeric region of eukaryotic chromosomes, where it replaces conventional histone H3 and together with centromere-specific-DNA-binding factors directs the assembly of active kinetochores.", "THe histone variant CENPA is preferentially located at Centromeric chromatin" ], "exact_answer": [ "Centromeres", "CENPA is preferentially localized in eukaryotic centromeres" ], "concepts": [ "http://www.uniprot.org/uniprot/CENPA_XENTR", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002503", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.uniprot.org/uniprot/CENPA_CHICK", "http://www.biosemantics.org/jochem#4278518", "http://www.uniprot.org/uniprot/CENPA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000775", "http://www.uniprot.org/uniprot/CENPA_CRIGR", "http://www.uniprot.org/uniprot/CENPA_DANRE", "http://www.uniprot.org/uniprot/CENPA_BOVIN", "http://www.uniprot.org/uniprot/CENPA_HUMAN", "http://www.uniprot.org/uniprot/CENPA_MOUSE" ], "type": "factoid", "id": "52fe52702059c6d71c000078", "snippets": [ { "offsetInBeginSection": 745, "offsetInEndSection": 774, "text": "centromere protein A (CENPA),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314512", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 434, "text": "Centromere activity of the alphoid YAC was suppressed at ectopic locations on the host chromosome, as indicated by the absent or reduced assembly of CENP-A and -C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12953060", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 357, "text": "Heterozygous and homozygous Cenpa-GFP fusion-protein mouse mutants, generated through targeted insertion of the green fluorescent protein (GFP) gene into the mouse Cenpa gene locus, show specific localized fluorescence at all the centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12906131", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 884, "text": "Co-immunoprecipitation assay demonstrates interaction between PARP-2 and its functional homolog PARP-1, constitutive centromere proteins Cenpa and Cenpb, and spindle checkpoint protein Bub3, but not with a third constitutive centromere protein Cenpc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12217960", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 824, "text": "Here we investigated the interaction of this protein with, and poly(ADP-ribosyl)ation of, three constitutive centromere proteins, Cenpa, Cenpb, and Cenpc, and a spindle checkpoint protein, Bub3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12011073", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1091, "text": "The evidence is consistent with the proposal of a critical epigenetic function for CENP-A in marking a chromosomal region for centromere formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10655499", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 319, "text": "CENPA is a member of the histone H3-like proteins and is thought to replace histone H3 in centromeric nucleosomes. CENPC is a DNA-binding protein that is located at the inner kinetochore plate of active mammalian centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9465302", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 57, "text": "ENPA/Cse4 assembles centromeric chromatin on diverse DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23439889", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 262, "text": "constitutive kinetochore proteins such as CENPA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21888900", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 579, "text": "A specific histone H3 variant, CENPA, replaces conventional histone H3 and together with centromere-specific-DNA-binding factors directs the assembly of active kinetochores", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20119530", "endSection": "abstract" } ] }, { "body": "In which proteins is the chromodomain present?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22705977", "http://www.ncbi.nlm.nih.gov/pubmed/22219182", "http://www.ncbi.nlm.nih.gov/pubmed/23239876", "http://www.ncbi.nlm.nih.gov/pubmed/16949368", "http://www.ncbi.nlm.nih.gov/pubmed/19279158", "http://www.ncbi.nlm.nih.gov/pubmed/21646535", "http://www.ncbi.nlm.nih.gov/pubmed/11956312", "http://www.ncbi.nlm.nih.gov/pubmed/20389031", "http://www.ncbi.nlm.nih.gov/pubmed/22086334", "http://www.ncbi.nlm.nih.gov/pubmed/17428788", "http://www.ncbi.nlm.nih.gov/pubmed/12186646", "http://www.ncbi.nlm.nih.gov/pubmed/21369828", "http://www.ncbi.nlm.nih.gov/pubmed/23071455", "http://www.ncbi.nlm.nih.gov/pubmed/21211724", "http://www.ncbi.nlm.nih.gov/pubmed/19399177", "http://www.ncbi.nlm.nih.gov/pubmed/22033296", "http://www.ncbi.nlm.nih.gov/pubmed/22768949", "http://www.ncbi.nlm.nih.gov/pubmed/22302795", 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"http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42384C4337300016", "o": "Chromodomain-helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B8LC70", "o": "http://linkedlifedata.com/resource/#_42384C4337300016" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42384C4337300017", "o": "http://linkedlifedata.com/resource/#_42384C4337300016" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42384C4337300016", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4335474B333300F", "o": "Chromodomain helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C5GK33", "o": "http://linkedlifedata.com/resource/#_4335474B333300F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4335474B33330010", "o": "http://linkedlifedata.com/resource/#_4335474B333300F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4335474B333300F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_43354A54543500F", "o": "Chromodomain helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C5JTT5", "o": "http://linkedlifedata.com/resource/#_43354A54543500F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_43354A5454350010", "o": "http://linkedlifedata.com/resource/#_43354A54543500F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_43354A54543500F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51375246303400A", "o": "Chromodomain protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q7RF04", "o": "http://linkedlifedata.com/resource/#_51375246303400A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_51375246303400B", "o": "http://linkedlifedata.com/resource/#_51375246303400A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_51375246303400A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D7WDJ2", "o": "http://linkedlifedata.com/resource/#_443757444A3200D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_443757444A3200E", "o": "http://linkedlifedata.com/resource/#_443757444A3200D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513235373332009", "o": "Chromodomain protein" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513235373332009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42394936463000A", "o": "Chromodomain protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B9I6F0", "o": "http://linkedlifedata.com/resource/#_42394936463000A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42394936463000B", "o": "http://linkedlifedata.com/resource/#_42394936463000A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42394936463000A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_43305654453100D", "o": "Chromodomain helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C0VTE1", "o": "http://linkedlifedata.com/resource/#_43305654453100D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_43305654453100E", "o": "http://linkedlifedata.com/resource/#_43305654453100D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_43305654453100D", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4238434154330016", "o": "Chromodomain-helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B8CAT3", "o": "http://linkedlifedata.com/resource/#_4238434154330016" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4238434154330017", "o": "http://linkedlifedata.com/resource/#_4238434154330016" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4238434154330016", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42364B35523200E", "o": "Chromodomain helicase hrp1" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B6K5R2", "o": "http://linkedlifedata.com/resource/#_42364B35523200E" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42364B35523200F", "o": "http://linkedlifedata.com/resource/#_42364B35523200E" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42364B35523200E", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42384E49523400F", "o": "Chromodomain helicase (Chd1), putative" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B8NIR4", "o": "http://linkedlifedata.com/resource/#_42384E49523400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42384E4952340010", "o": "http://linkedlifedata.com/resource/#_42384E49523400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42384E49523400F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_433147344D3400F", "o": "Chromodomain helicase hrp3" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C1G4M4", "o": "http://linkedlifedata.com/resource/#_433147344D3400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_433147344D340010", "o": "http://linkedlifedata.com/resource/#_433147344D3400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_433147344D3400F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_44304E45343000A", "o": "Chromodomain protein, putative" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44304E45343000A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513759525130009", "o": "Chromodomain Y-like protein" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513759525130009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_43364839453100F", "o": "Chromodomain helicase hrp3" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C6H9E1", "o": "http://linkedlifedata.com/resource/#_43364839453100F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4336483945310010", "o": "http://linkedlifedata.com/resource/#_43364839453100F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_43364839453100F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D0NPW7", "o": "http://linkedlifedata.com/resource/#_44304E50573700A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_44304E50573700B", "o": "http://linkedlifedata.com/resource/#_44304E50573700A" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_443256545539009", "o": "Chromodomain-containing protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D2VTU9", "o": "http://linkedlifedata.com/resource/#_443256545539009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_44325654553900A", "o": "http://linkedlifedata.com/resource/#_443256545539009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_443256545539009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513458363931009", "o": "Chromodomain protein, putative" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513458363931009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513759525039009", "o": "Chromodomain Y protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q7YRP9", "o": "http://linkedlifedata.com/resource/#_513759525039009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_51375952503900A", "o": "http://linkedlifedata.com/resource/#_513759525039009" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513759525039009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5139354B543500C", "o": "Y chromosomal chromodomain protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q95KT5", "o": "http://linkedlifedata.com/resource/#_5139354B543500C" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_5139354B543500D", "o": "http://linkedlifedata.com/resource/#_5139354B543500C" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_5139354B543500C", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4139543534350010", "o": "SNF2 family chromodomain-helicase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/A9T545", "o": "http://linkedlifedata.com/resource/#_4139543534350010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4139543534350011", "o": "http://linkedlifedata.com/resource/#_4139543534350010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4139543534350010", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_433146484235008", "o": "Chromodomain-containing protein" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C1FHB5", "o": "http://linkedlifedata.com/resource/#_433146484235008" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_433146484235009", "o": "http://linkedlifedata.com/resource/#_433146484235008" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_433146484235008", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4339534A48310011", "o": "Chromodomain helicase hrp3" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/C9SJH1", "o": "http://linkedlifedata.com/resource/#_4339534A48310011" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4339534A48310012", "o": "http://linkedlifedata.com/resource/#_4339534A48310011" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4339534A48310011", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_44304E41333900A", "o": "Chromodomain protein, putative" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D0NA39", "o": "http://linkedlifedata.com/resource/#_44304E41333900A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_44304E41333900B", "o": "http://linkedlifedata.com/resource/#_44304E41333900A" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44304E41333900A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_45334B535A380010", "o": "Chromodomain helicase hrp1" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/E3KSZ8", "o": "http://linkedlifedata.com/resource/#_45334B535A380010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_45334B535A380011", "o": "http://linkedlifedata.com/resource/#_45334B535A380010" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_45334B535A380010", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/ecName", "s": "http://linkedlifedata.com/resource/#_513641594B39009", "o": "2.3.1.48" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513641594B39009", "o": "Chromodomain Y-like protein" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q6AYK9", "o": "http://linkedlifedata.com/resource/#_513641594B39009" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_513641594B39009", "o": "CDY-like" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11683673", "o": "1811" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44325647443600A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4531465947360019", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513957544B320013", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_443257314B3600A", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_44304E453935001B", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_443256464734009", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_423656414439009", "o": "http://purl.uniprot.org/core/Structured_Name" } ], "ideal_answer": [ "The chromodomain (chromatin organizer modifier domain) is a highly conserved motif, 40-50 amino acids in length, present in a wide range of animal and plant proteins involved in chromatin organization. Chromodomain-containing proteins can be classified into boader families based, particularly, on the presence of other types of domains. Chromodomain is present in: the heterochromatin proteins HP1 alpha and HP1 beta, chromointgrases (e.g. Tf1 integrase) the chromodomain helicase DNA-binding proteins (CHD) and CHD 1-like (CHD1L), CReMM (chromatin-related mesenchymal modulator), dna methyltransferase 3 (cmt3), the chromointegrase of the LTR-retrotransposons, the Polycomb group (PcG) proteins, the mouse Polycomb homologs (Cbx2, Cbx4, Cbx6, Cbx7, Cbx8), the chromodomain Y chromosome (CDY) family of proteins and the CDY-like protein (CDYL), the histone acetyltransferases TgMYST-A and \u2013B, MRG-1 and -15 (MORF4-Related Gene on chromosome 15), ADP/ATP translocase 1, MPP8, MSL3, NlMof, Chp1, Chriz, dMi-2, Corto, cpSRP43, KISMET, PICKLE (PKL), ScoHET1 and ScoHET2.\n" ], "exact_answer": [ [ "HP1 alpha" ], [ "CHD proteins", "Chromodomain helicase DNA-binding protein" ], [ "CReMM" ], [ "cmt3" ], [ "chromointegrases" ], [ "Polycomb group (PcG) proteins" ], [ "Cbx2" ], [ "TgMYST-A" ], [ "MRG15" ], [ "MSL3" ], [ "Swi6" ], [ "Chp1" ], [ "dMi-2" ], [ "Corto" ], [ "ScoHET1" ], [ "cpSRP43" ], [ "CDY", "chromodomain Y chromosome" ], [ "transposable elements" ], [ "like heterochromatin protein", "LHP1" ], [ "ADP/ATP translocase 1" ], [ "CDYL", "CDY-like protein" ], [ "CHD1L", "CHD1-like" ], [ "NlMof" ], [ "TIP60" ], [ "Kismet" ], [ "Chriz" ], [ "PICKLE", "PKL" ], [ "HP1 beta" ], [ "HP1 gamma" ], [ "TgMYST \u2013B" ], [ "Cbx4" ], [ "Cbx6" ], [ "Cbx7" ], [ "Cbx8" ], [ "ScoHET2" ], [ "Cbx3" ], [ "MPP8" ], [ "MRG1" ] ], "concepts": [ "http://www.uniprot.org/uniprot/CHD3_DROME", "http://www.uniprot.org/uniprot/CHD7_HUMAN", "http://www.uniprot.org/uniprot/CHD4_HUMAN", "http://www.uniprot.org/uniprot/CHD1_MOUSE", "http://www.uniprot.org/uniprot/CHD7_CHICK", "http://www.uniprot.org/uniprot/CHD1L_DANRE", "http://www.uniprot.org/uniprot/CDYL_RAT", "http://www.uniprot.org/uniprot/CDY2_HUMAN", "http://www.uniprot.org/uniprot/CHD8_XENTR", "http://www.uniprot.org/uniprot/CDYL_MOUSE", "http://www.uniprot.org/uniprot/CHD1L_BOVIN", "http://www.uniprot.org/uniprot/CHD9_HUMAN", "http://www.uniprot.org/uniprot/HRP3_SCHPO", "http://www.uniprot.org/uniprot/CHD8_DANRE", "http://www.uniprot.org/uniprot/CHD6_HUMAN", "http://www.uniprot.org/uniprot/CHD8_HUMAN", "http://www.uniprot.org/uniprot/CHD1L_MOUSE", "http://www.uniprot.org/uniprot/CDYL2_HUMAN", "http://www.uniprot.org/uniprot/CDYL1_HUMAN", "http://www.uniprot.org/uniprot/CHDM_DROME", "http://www.uniprot.org/uniprot/CHD9_MOUSE", "http://www.uniprot.org/uniprot/CHD1_HUMAN", "http://www.uniprot.org/uniprot/CHD3_HUMAN", "http://www.uniprot.org/uniprot/CHD2_HUMAN", "http://www.uniprot.org/uniprot/CHD3_CAEEL", "http://www.uniprot.org/uniprot/CHD1_DROME", "http://www.uniprot.org/uniprot/CHD1L_HUMAN", "http://www.uniprot.org/uniprot/CHD4_MOUSE", "http://www.uniprot.org/uniprot/HRP1_SCHPO", "http://www.uniprot.org/uniprot/CHD7_MOUSE", "http://www.uniprot.org/uniprot/CHD5_HUMAN", "http://www.uniprot.org/uniprot/CHD1_BOMMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.uniprot.org/uniprot/CHD8_MOUSE", "http://www.uniprot.org/uniprot/CDY1_HUMAN", "http://www.uniprot.org/uniprot/CHD8_RAT", "http://www.uniprot.org/uniprot/CHD1_CHICK" ], "type": "list", "id": "517137c18ed59a060a000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Chromodomain helicase DNA-binding protein 2 affects the repair of X-ray and UV-induced DNA damage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223433", "endSection": "title" }, { "offsetInBeginSection": 408, "offsetInEndSection": 734, "text": "Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription. In an effort to understand the physiological role of one of the CHD members in a mammalian model system, we developed a mutant mouse model for the Chd2 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223433", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Crystal structure of the chromodomain helicase DNA-binding protein 1 (Chd1) DNA-binding domain in complex with DNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033927", "endSection": "title" }, { "offsetInBeginSection": 581, "offsetInEndSection": 969, "text": "Because, in plants, DNA methylation can serve as a signal for H3-lysine9-dimethylation (H3K9me2), and subsequently for non-CG-context DNA methylation, SET-domain histone methyltransferase and chromodomain dna methyltransferase 3 (cmt3) mutations were introgressed. In suvh4 suvh5 suvh6 and cmt3 mutants, H3K9me2 associated with lacO repeats is diminished, but homologous pairing persists.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21830056", "endSection": "sections.0" }, { "offsetInBeginSection": 197, "offsetInEndSection": 341, "text": "Mutations in CHD7, the gene encoding chromodomain helicase DNA binding protein 7, are present in 60-80% of individuals with the CHARGE syndrome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596839", "endSection": "sections.0" }, { "offsetInBeginSection": 1252, "offsetInEndSection": 1414, "text": "Chromodomain is present in the integrase structures of blastopia and 412 subgroup LTR-retrotransposons and may facilitate the process of non-specific integration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21369828", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "The CHARGE syndrome is a multiple congenital malformation syndrome that usually results from deletion or heterozygous loss of function mutations of the chromodomain helicase DNA-binding protein 7 (CHD7) gene at 8q12.1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21094707", "endSection": "sections.0" }, { "offsetInBeginSection": 193, "offsetInEndSection": 374, "text": "A causative mutation within the chromodomain helicase DNA-binding protein-7 gene, which plays an important role in the embryonic development, is present in 2/3 of affected patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20860631", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "CHD1 is a subfamily member of the CHD family, which possesses a chromodomain, a helicase domain, and a DNA-binding domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20568999", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The chromatin organizer modifier domain (chromodomain) is present in proteins that contribute to chromatin organization and mediates their binding to methylated histone H3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20493168", "endSection": "sections.0" }, { "offsetInBeginSection": 761, "offsetInEndSection": 1442, "text": "Mass spectrometric analysis revealed serine-42, a conserved amino acid in the chromodomain, as a phosphorylation site of Cbx2. Phosphorylation of the chromodomain of Cbx2 on this residue in vitro resulted in a reduced level of binding to an H3 peptide containing trimethylated lysine-9 as well as an increase in the extent of binding to an H3 peptide containing trimethylated lysine-27, suggesting that such phosphorylation changes the binding specificity of Cbx2 for modified histone H3. Phosphorylation of the chromodomain of Cbx2 may therefore serve as a molecular switch that affects the reading of the histone modification code and thereby controls epigenetic cellular memory.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20493168", "endSection": "sections.0" }, { "offsetInBeginSection": 327, "offsetInEndSection": 501, "text": "Here we identify the ATP-dependent chromatin remodeling factor chromodomain helicase DNA-binding protein 8 (CHD8) as a novel coregulator of androgen-responsive transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20308527", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19279158", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Two new chromodomain-containing proteins that associate with heterochromatin in Sciara coprophila chromosomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19205716", "endSection": "title" }, { "offsetInBeginSection": 219, "offsetInEndSection": 410, "text": "Both proteins, ScoHET1 of 37 kDa and ScoHET2 of 44 kDa, display two chromodomain motifs that contain the conserved residues essential for the recognition of methylated histone H3 at lysine 9.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19205716", "endSection": "sections.0" }, { "offsetInBeginSection": 637, "offsetInEndSection": 796, "text": "In this study, we present a detailed histomorphologic characterization of mice containing a mutation in the chromodomain helicase DNA-binding protein 2 (Chd2).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19142019", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450745", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Previous studies have shown two homologous chromodomain modules in the HP1 and Polycomb proteins exhibit discriminatory binding to related methyllysine residues (embedded in ARKS motifs) of the histone H3 tail.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450745", "endSection": "sections.0" }, { "offsetInBeginSection": 440, "offsetInEndSection": 667, "text": "In vertebrates, HP1-like chromodomains are also present in the chromodomain Y chromosome (CDY) family of proteins adjacent to a putative catalytic motif. The human genome encodes three CDY family proteins, CDY, CDYL, and CDYL2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450745", "endSection": "sections.0" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1320, "text": "The CDY chromodomain exhibits discriminatory binding to lysine-methylated ARK(S/T) motifs, whereas the CDYL2 chromodomain binds with comparable strength to multiple ARK(S/T) motifs. Interestingly, subtle amino acid changes in the CDYL chromodomain prohibit such binding interactions in vitro and in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450745", "endSection": "sections.0" }, { "offsetInBeginSection": 487, "offsetInEndSection": 883, "text": "We assessed mRNA transcript abundance of seven genes that code for proteins with established roles in epigenetically-mediated gene silencing [transcriptional co-repressor SIN3A, DNA (cytosine-5-) methyltransferase 1, methyl CpG binding protein 2, chromodomain helicase DNA binding protein 4, histone binding protein rbbp4, histone deacetylase 1 and nuclear receptor co-repressor 2] using qRT-PCR.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18369641", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "CHD7 is a member of the chromodomain helicase DNA binding domain (CHD) family of ATP-dependent chromatin remodelling enzymes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17603073", "endSection": "sections.0" }, { "offsetInBeginSection": 284, "offsetInEndSection": 368, "text": "The cysteine-rich CXXC domains of MBD1 bound to Ring1b and the chromodomain of hPc2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17428788", "endSection": "sections.0" }, { "offsetInBeginSection": 228, "offsetInEndSection": 495, "text": "Methylation of lysine 9 within histone H3 and the subsequent binding of the chromodomain protein heterochromatin protein 1 (HP1) are thought to initiate heterochromatin formation in vivo and to propagate a heterochromatic state lasting through several cell divisions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17101786", "endSection": "sections.0" }, { "offsetInBeginSection": 200, "offsetInEndSection": 320, "text": "Here, we show that the SNF2-like chromodomain helicase protein CHD8 interacts with the insulator binding protein CTCF. C", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16949368", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The chromodomain (CD) of the Drosophila Polycomb protein exhibits preferential binding affinity for histone H3 when trimethylated at lysine 27.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16537902", "endSection": "sections.0" }, { "offsetInBeginSection": 246, "offsetInEndSection": 362, "text": "Despite a high degree of conservation, the Cbx chromodomains display significant differences in binding preferences.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16537902", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Three-dimensional solution structures of the chromodomains of cpSRP43.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16183644", "endSection": "title" }, { "offsetInBeginSection": 194, "offsetInEndSection": 284, "text": "Recently, three functionally distinct chromodomains (CDs) have been identified in cpSRP43.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16183644", "endSection": "sections.0" }, { "offsetInBeginSection": 520, "offsetInEndSection": 613, "text": "The C-terminal helical segment typically found in the nuclear chromodomains is absent in CD1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16183644", "endSection": "sections.0" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1139, "text": "Critical comparison of the structures of the chromodomains of cpSRP43 with those found in nuclear chromodomain proteins revealed that the diverse protein-protein interactions mediated by the CDs appear to stem from the differences that exist in the surface charge potentials of each CD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16183644", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Characterization and functional analysis of CReMM, a novel chromodomain helicase DNA-binding protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16095617", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 422, "text": "The present study describes a newly identified protein named CReMM (chromatin-related mesenchymal modulator). The protein was studied by bioinformatic means and classified as a member of the third subfamily of chromodomain helicase DNA-binding proteins (CHD). In silico translation defined CReMM as a multiple domains protein including two chromodomains, SNF2/ATPase, helicase C domain and an A/T-DNA-binding domain (DBD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16095617", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Identification and analysis of chromodomain-containing proteins encoded in the mouse transcriptome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12819141", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "The chromodomain is 40-50 amino acids in length and is conserved in a wide range of chromatic and regulatory proteins involved in chromatin remodeling. Chromodomain-containing proteins can be classified into families based on their broader characteristics, in particular the presence of other types of domains, and which correlate with different subclasses of the chromodomains themselves.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12819141", "endSection": "sections.0" }, { "offsetInBeginSection": 434, "offsetInEndSection": 622, "text": "Here we show that the chromodomain of CMT3 can directly interact with the N-terminal tail of histone H3, but only when it is simultaneously methylated at both the H3K9 and H3K27 positions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15457214", "endSection": "sections.0" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1027, "text": "In addition to the canonical MYST HAT catalytic domain, both TgMYST-A and -B possess an atypical C2HC zinc finger and a chromodomain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339723", "endSection": "sections.0" }, { "offsetInBeginSection": 416, "offsetInEndSection": 753, "text": "Clr7 and Clr8 are required for localization of the Swi6 chromodomain protein and for histone H3 lysine 9 methylation, thereby influencing not only mating-type switching but also transcriptional silencing in all previously characterized heterochromatic regions, chromosome segregation, and meiotic recombination in the mating-type region.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16157682", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12397079", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "MRG15 is a novel chromodomain protein that is a member of a family of genes related to MORF4. MORF4 (mortality factor on chromosome 4) induces senescence in a subset of human tumor cell lines.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12397079", "endSection": "sections.0" }, { "offsetInBeginSection": 640, "offsetInEndSection": 1201, "text": "Analysis of deletion mutants of MRG15 indicated that the leucine zipper at the C-terminal region of MRG15 was important for the protein associations in MAF1 and that the N-terminal chromodomain was required for the assembly of the MAF2 protein complex. Consistent with these data was the fact that a histone acetyltransferase activity associated with MRG15 was lost when the chromodomain was deleted and that both mutant MRG15 proteins failed to activate the B-myb promoter. The various mechanisms by which MRG15 could activate gene transcription are discussed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12397079", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The chromodomain (CD) is a highly conserved motif present in a variety of animal and plant proteins, and its probable role is to assemble a variety of macromolecular complexes in chromatin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11956312", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11859155", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 596, "text": "The chromodomain of the HP1 family of proteins recognizes histone tails with specifically methylated lysines. Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing. The histone tail inserts as a beta strand, completing the beta-sandwich architecture of the chromodomain. The methylammonium group is caged by three aromatic side chains, whereas adjacent residues form discerning contacts with one face of the chromodomain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11859155", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "The MORF4-Related Gene on chromosome 15 (MRG15) is a member of a novel family of genes originally identified in studies to reveal cell senescence-inducing factors. MRG15 contains several predicted protein motifs, including a nuclear localization signal, a helix-loop-helix region, a leucine zipper, and a chromodomain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11500496", "endSection": "sections.0" }, { "offsetInBeginSection": 737, "offsetInEndSection": 1036, "text": "Four alleles of dMi-2 mutants were further characterized in molecular nature; dMi-2(BL1) was found to have a mutation in the ATP-binding motif of the ATPase domain, dMi-2(BL7) in the core histidine of the first plant homeodomain zinc finger and dMi-2(BL12) in a conserved serine in the chromodomain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12137948", "endSection": "sections.0" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1443, "text": "These analyses also suggest that the msl-3/MRG15 duplication occurred after the fungus/animal split, while an independent duplication occurred in plants. The proteins encoded by these genes have similar structures, including a putative chromodomain close to their N-terminal end and a putative leucine zipper at their C-terminus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10908644", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "CHD1 interacts with SSRP1 and depends on both its chromodomain and its ATPase/helicase-like domain for proper association with chromatin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10199952", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8663349", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8460153", "endSection": "title" }, { "offsetInBeginSection": 472, "offsetInEndSection": 650, "text": "A Southern blot analysis indicated that this protein, which we have named CHD-1, for chromodomain-helicase-DNA-binding protein, is present in most, if not all, mammalian species.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8460153", "endSection": "sections.0" }, { "offsetInBeginSection": 271, "offsetInEndSection": 464, "text": "Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-\u03b3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23471993", "endSection": "sections.0" }, { "offsetInBeginSection": 195, "offsetInEndSection": 471, "text": "Chromodomain helicase DNA-binding protein 4 (CHD4), the defining subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is a nucleosome-remodeling protein of the SNF2/ISWI2 family, members of which contain two chromo domains and an ATP-dependent helicase module.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23417793", "endSection": "sections.0" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1320, "text": "Among those proteins with >40% regulation were Macrophage Capping protein (CAPG) and Chromodomain Helicase DNA binding protein 4 (CHD4) proteins which were significantly upregulated by pp32r1 and pp32r1Y140H overexpression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23403278", "endSection": "sections.0" }, { "offsetInBeginSection": 316, "offsetInEndSection": 448, "text": "This heterochromatin coordinates expression levels by associating with a chromodomain protein Chp1 and an antisilencing factor Epe1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388053", "endSection": "sections.0" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1257, "text": "Within NCCs, Brg1 partners with chromatin remodeler Chromodomain-helicase-DNA-binding protein 7 (Chd7) on the PlexinA2 promoter to activate PlexinA2, which encodes a receptor for semaphorin to guide NCCs into the OFT.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23319608", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Chromodomain Helicase DNA binding protein 5 (CHD5) is a tumor suppressor mapping to 1p36, a genomic region that is frequently deleted in human cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318260", "endSection": "sections.0" }, { "offsetInBeginSection": 271, "offsetInEndSection": 513, "text": "Here, we identify ENHANCED PHOTOMORPHOGENIC1 (EPP1), previously known as PICKLE (PKL), an ATP-dependent chromatin remodeling factor of the chromodomain/helicase/DNA binding family, as a repressor of photomorphogenesis in Arabidopsis thaliana.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314848", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Chromodomain on Y-like (CDYL) is a chromodomain protein that has sequence homology to members of the enoyl CoA hydratase family.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23282990", "endSection": "sections.0" }, { "offsetInBeginSection": 232, "offsetInEndSection": 850, "text": "Our previous structural work demonstrated that a coiled-coil interaction between MBD2 and GATA zinc finger domain containing 2A (GATAD2A/p66\u03b1) proteins recruits the chromodomain helicase DNA-binding protein (CHD4/Mi2\u03b2) to the NuRD complex and is necessary for MBD2-mediated DNA methylation-dependent gene silencing in vivo (Gnanapragasam, M. N., Scarsdale, J. N., Amaya, M. L., Webb, H. D., Desai, M. A., Walavalkar, N. M., Wang, S. Z., Zu Zhu, S., Ginder, G. D., and Williams, D. C., Jr. (2011) p66\u03b1-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23239876", "endSection": "sections.0" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1132, "text": "Sequence analysis showed that NlElp3 contains GNAT-type HAT domain and Radical SAM domain, and NlMof contains chromodomain and MOZ-SAS acetyltransferase domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23142031", "endSection": "sections.0" }, { "offsetInBeginSection": 152, "offsetInEndSection": 454, "text": "We examined requirements for individual domains of chromodomain helicase DNA-binding protein 4 (CHD4), a core catalytic component of NuRD complexes, as well as the NuRD subunit methyl-binding domain protein 2 (MBD2) and methylated DNA, for NuRD function in the context of tissue-specific transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071088", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "OBJECTIVE: Chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L) is an SNF2-like transcription factor involved in the development of human hepatocellular carcinoma (HCC).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022495", "endSection": "sections.0" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1347, "text": "Twelve rare copy number variants segregate with talipes equinovarus in multiplex pedigrees, and contain the developmentally expressed transcription factors and transcriptional regulators PITX1, TBX4, HOXC13, UTX, CHD (chromodomain protein)1, and RIPPLY2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892537", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "OBJECTIVE: Chromodomain helicase DNA-binding protein 5 (CHD5) plays a role in normal neural development and in tumorigenesis of various human cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22855185", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The chromodomain, helicase, DNA-binding protein 5 (CHD5) is a chromatin remodeling enzyme which is implicated in tumor suppression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22834704", "endSection": "sections.0" }, { "offsetInBeginSection": 543, "offsetInEndSection": 663, "text": "The methyl-mark determines a highly flexible and very dynamic interaction of the chromodomain of hHP1\u03b2 with the H3-tail.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815475", "endSection": "sections.0" }, { "offsetInBeginSection": 359, "offsetInEndSection": 556, "text": "To test this hypothesis, we performed a comprehensive molecular dynamics study in which we analyzed a crystallographically defined complex that involves the HP1 chromodomain and an H3 tail peptide.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768949", "endSection": "sections.0" }, { "offsetInBeginSection": 567, "offsetInEndSection": 754, "text": "Whereas the molecular target of the MRG15 chromodomain (CD) has been suggested to be H3K36me(2/3), the precise molecular target of the Pf1 plant homeodomain 1 (PHD1) has remained elusive.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728643", "endSection": "sections.0" }, { "offsetInBeginSection": 81, "offsetInEndSection": 279, "text": "Chp1, a chromodomain (CD) protein, forms the Ago1-containing RNA-induced transcriptional silencing (RITS) complex and recruits siRNA-bound RITS to methylated histone H3 lysine 9 (H3K9me) via its CD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727667", "endSection": "sections.0" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1076, "text": "In addition, cells expressing S473A also displayed defective mobilization of the HP1-\u03b2 chromodomain protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22715096", "endSection": "sections.0" }, { "offsetInBeginSection": 300, "offsetInEndSection": 488, "text": "CHD7 is a chromodomain-containing, ATP dependent helicase protein that is highly expressed in the developing ear and is required for semicircular canal development in both humans and mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22705977", "endSection": "sections.0" }, { "offsetInBeginSection": 734, "offsetInEndSection": 997, "text": "Moreover, the LTR retrotransposon fraction in BAC clones harboring genes is disproportionately composed of chromodomain-containing Gypsy LTR retrotransposons ('chromoviruses'), and the majority of the intact chromoviruses contain tandem chromodomain duplications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22691070", "endSection": "sections.0" }, { "offsetInBeginSection": 483, "offsetInEndSection": 633, "text": "Stimulated by positively charged residues in the hinge region, RNA competes with methylated histone H3K9 for binding to the chromodomain of HP1(Swi6).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683269", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "CHD7 is one of the nine members of the chromodomain helicase DNA-binding family of ATP-dependent chromatin remodeling enzymes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22646239", "endSection": "sections.0" }, { "offsetInBeginSection": 1847, "offsetInEndSection": 2069, "text": "Therefore, p53, ZNF237, and Chromodomain helicase DNA-binding protein 3 inhibit the function ER Ca\u00b2\u207a leak channels to regulate both ER and cytoplasmic Ca\u00b2\u207a levels and may potentially control Ca\u00b2\u207a-signaling function of PS1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22607268", "endSection": "sections.0" }, { "offsetInBeginSection": 79, "offsetInEndSection": 358, "text": "We show that chromodomain helicase DNA-binding domain 2 (Chd2), a SNF2 chromatin remodelling enzyme family member, interacts with MyoD and myogenic gene regulatory sequences to specifically mark these loci via deposition of the histone variant H3.3 prior to cell differentiation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22569126", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Analysis of the Neurospora crassa chromodomain protein CDP-2, a component of a newly characterized HP1-containing complex, reveals a second gene-silencing mechanism and provides insights into the dynamic nature of chromatin domains that possess shared components.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22551706", "endSection": "sections.0" }, { "offsetInBeginSection": 1552, "offsetInEndSection": 1799, "text": "We state that the non-tumorogenic potential of bitumen transformant in nude/SCID mice can be attributed to the downregulation of galectin-1, chromodomain helicase DNA-binding protein 1-like gene, and membrane-associated guanylate kinase 2 protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22528993", "endSection": "sections.0" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1205, "text": "Mutagenesis of Tf1 integrase revealed that the complete Tf1 integrase protein (excluding its chromodomain) is required for stimulating the Tf1 RT primer removal activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22491446", "endSection": "sections.0" }, { "offsetInBeginSection": 212, "offsetInEndSection": 362, "text": "About 80% of patients with a clinical diagnose, have a mutation or a deletion in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22462537", "endSection": "sections.0" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1208, "text": "Owing to different polyadenylation sites and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419124", "endSection": "sections.0" }, { "offsetInBeginSection": 236, "offsetInEndSection": 398, "text": "Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22302795", "endSection": "sections.0" }, { "offsetInBeginSection": 408, "offsetInEndSection": 576, "text": "Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223433", "endSection": "sections.0" }, { "offsetInBeginSection": 545, "offsetInEndSection": 687, "text": "Here, we report that chromodomain helicase DNA-binding protein 4 (CHD4) is a novel BRIT1 binding partner that regulates the HR repair process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22219182", "endSection": "sections.0" }, { "offsetInBeginSection": 315, "offsetInEndSection": 460, "text": "Here, we report that the chromodomain-containing protein MRG-1 is an important factor for genomic integrity in meiosis in Caenorhabditis elegans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22212480", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The chromodomain protein, Chromator, can be divided into two main domains, a NH(2)-terminal domain (NTD) containing the chromodomain (ChD) and a COOH-terminal domain (CTD) containing a nuclear localization signal.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22203189", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Chromodomain helicase DNA binding protein 5 (CHD5) is a potent tumor suppressor that serves as a master regulator of a tumor-suppressive network.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22186629", "endSection": "sections.0" }, { "offsetInBeginSection": 466, "offsetInEndSection": 631, "text": "By high-resolution tiling array CGH, the smallest common deletion targeted just one gene, the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22179824", "endSection": "sections.0" }, { "offsetInBeginSection": 629, "offsetInEndSection": 786, "text": "Here we report direct evidence for presynaptic pairing activity intrinsic to non-PC regions, which is facilitated by a conserved chromodomain protein, MRG-1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22172672", "endSection": "sections.0" }, { "offsetInBeginSection": 390, "offsetInEndSection": 456, "text": "The chromodomain of MPP8 recognizes the dimethylated Dnmt3aK44me2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086334", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Members of the chromodomain helicase DNA-binding (CHD) family of proteins are thought to regulate gene expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22083958", "endSection": "sections.0" }, { "offsetInBeginSection": 161, "offsetInEndSection": 284, "text": "It has been shown that the methylation mark of vertebrate histone H1 is specifically recognized by the chromodomain of HP1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22083954", "endSection": "sections.0" }, { "offsetInBeginSection": 602, "offsetInEndSection": 761, "text": "To this end, we have performed mutation studies on the Drosophila HP1\u03b1 chromodomain, which binds H3K9Me(2) and H3K9Me(3) with approximately equal affinities.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22052799", "endSection": "sections.0" }, { "offsetInBeginSection": 110, "offsetInEndSection": 276, "text": "We are interested in defining which elements of the chromodomain helicase DNA-binding protein 1 (Chd1) remodeler are necessary and sufficient for sliding nucleosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22039057", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Chromatin remodelers are ATP-dependent machines that dynamically alter the chromatin packaging of eukaryotic genomes by assembling, sliding, and displacing nucleosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033927", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Ocular coloboma, heart malformation, choanal atresia, retardation of growth and/or development, genital hypoplasia, and ear anomalies associated with deafness (CHARGE) syndrome is a rare, usually sporadic, autosomal dominant disorder, caused by mutations within the CHD7 (chromodomain helicase DNA-binding protein 7) gene, in nearly 70% of cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033296", "endSection": "sections.0" }, { "offsetInBeginSection": 366, "offsetInEndSection": 568, "text": "Here we report that the chromodomain-containing protein CDYL specifically recognizes di- and tri-methylated H3K27 (H3K27me2 and H3K27me3) and directly interacts with EZH2, the catalytic subunit of PRC2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009739", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Murine Chd1 (chromodomain helicase DNA-binding protein 1), a chromodomain-containing chromatin remodeling protein, is necessary for embryonic stem (ES) cell pluripotency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979373", "endSection": "sections.0" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1055, "text": "Among those genes, zinc finger helicase (ZFH), also termed chromodomain-helicase-DNA-binding protein 3 (Chd3), was one of the highly expressed transcripts in tentative cementoblasts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21972924", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "UNLABELLED: Emerging evidence implicates the chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) as a specific oncogene in human hepatocellular carcinoma (HCC).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953552", "endSection": "sections.0" }, { "offsetInBeginSection": 230, "offsetInEndSection": 349, "text": "Here, we investigate the function of chromodomain helicase DNA binding protein 7 (chd7) during zebrafish somitogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21901784", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875659", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: The CHD5 gene located on 1p36 encodes a protein-chromodomain helicase DNA-binding protein 5. CHD5 has been shown to be a tumor suppressor gene candidate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21860208", "endSection": "sections.0" }, { "offsetInBeginSection": 581, "offsetInEndSection": 845, "text": "Because, in plants, DNA methylation can serve as a signal for H3-lysine9-dimethylation (H3K9me2), and subsequently for non-CG-context DNA methylation, SET-domain histone methyltransferase and chromodomain dna methyltransferase 3 (cmt3) mutations were introgressed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21830056", "endSection": "sections.0" }, { "offsetInBeginSection": 122, "offsetInEndSection": 293, "text": "Previously, we have shown that the chromodomain protein Chriz and the zinc-finger protein Z4 are essentially required for the maintenance of polytene chromosome structure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21799255", "endSection": "sections.0" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1214, "text": "In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21730028", "endSection": "sections.0" }, { "offsetInBeginSection": 179, "offsetInEndSection": 411, "text": "RESULTS: Here we demonstrated that chromobox protein homolog 3 (Cbx3) is crucial for SMC differentiation from stem cells and that the chromodomain and chromoshadow domain of Cbx3 are responsible for Cbx3-induced SMC differentiation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21659642", "endSection": "sections.0" }, { "offsetInBeginSection": 323, "offsetInEndSection": 468, "text": "Fractionation of the extract identified a single protein, chromodomain helicase DNA binding protein 1 (Chd1), capable of the remodeling activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21646535", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Chromodomain helicase DNA-binding protein 5 (CHD5) has been found to be a candidate tumor suppressor gene (TSG) in malignant neural tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21636313", "endSection": "sections.0" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1244, "text": "Similarly, CenH3-GFP distribution was altered in the absence of HP1, the chromodomain protein that binds to H3K9me3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505064", "endSection": "sections.0" }, { "offsetInBeginSection": 463, "offsetInEndSection": 631, "text": "ChIP-Seq reveals that KDM5B is predominantly targeted to intragenic regions and that it is recruited to H3K36me3 via an interaction with the chromodomain protein MRG15.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21448134", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "OBJECTIVE: Chromodomain helicase DNA-binding protein (CHD) is a regulator of the chromatin remodelling process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21447119", "endSection": "sections.0" }, { "offsetInBeginSection": 239, "offsetInEndSection": 328, "text": "We determined the crystal structure of MPP8 chromodomain in complex with H3K9me3 peptide.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21419134", "endSection": "sections.0" }, { "offsetInBeginSection": 338, "offsetInEndSection": 550, "text": "On this gene the chromodomain protein HP1\u03b3, frequently defined as a transcriptional repressor, facilitates inclusion of the alternative exons via a mechanism involving decreased RNA polymerase II elongation rate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358630", "endSection": "sections.0" }, { "offsetInBeginSection": 492, "offsetInEndSection": 703, "text": "Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core component of the NuRD complex and contains a nucleosome remodeling ATPase domain along with two chromodomains and two plant homeodomain (PHD) fingers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21278251", "endSection": "sections.0" }, { "offsetInBeginSection": 289, "offsetInEndSection": 346, "text": "H3-Lys-9-Me2 interacts with the chromodomain of Swi6/HP1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21224386", "endSection": "sections.0" }, { "offsetInBeginSection": 108, "offsetInEndSection": 270, "text": "The chromodomain (CD) of HP1 proteins specifically recognizes the methyl mark on H3 peptides, but the same extent of specificity is not observed within chromatin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211724", "endSection": "sections.0" }, { "offsetInBeginSection": 328, "offsetInEndSection": 468, "text": "We have performed simulations on models of chromodomain helicase DNA-binding protein 1 complexed with a variety of histone H3 modifications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21195088", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "CHARGE syndrome is an autosomal dominant multisystem disorder caused by mutation in the CHD7 gene, encoding chromodomain helicase DNA-binding protein 7. Molecular diagnostic testing for CHD7 mutation has been available in a clinical setting since 2005.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21158681", "endSection": "sections.0" }, { "offsetInBeginSection": 613, "offsetInEndSection": 822, "text": "In this work we identified Kismet, a chromodomain-containing protein of the SNF2-like family of ATPases, as a novel component of the hedgehog transcriptional repression mechanism in anterior compartment cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21146514", "endSection": "sections.0" } ] }, { "body": "What is Genomicus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20185404", "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "http://www.ncbi.nlm.nih.gov/pubmed/25378326" ], "ideal_answer": [ "Genomicus had been developed as a database and a browser to study gene synteny in modern and ancestral genomes. It allows easy comparative genomic visualization in >150 eukaryote genomes and in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. The graphical modules of Genomicus show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and facilitate the study of the evolution of a locus through homology relationships. The Genomicus server provides access to ancestral gene orders, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064878", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026801" ], "type": "summary", "id": "56b3efc38525abca1e000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Genomicus: a database and a browser to study gene synteny in modern and ancestral genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185404", "endSection": "title" }, { "offsetInBeginSection": 470, "offsetInEndSection": 917, "text": "Here we present Genomicus, a new synteny browser that can represent and compare unlimited numbers of genomes in a broad phylogenetic view. In addition, Genomicus includes reconstructed ancestral gene organization, thus greatly facilitating the interpretation of the data.AVAILABILITY: Genomicus is freely available for online use at http://www.dyogen.ens.fr/genomicus while data can be downloaded at ftp://ftp.biologie.ens.fr/pub/dyogen/genomicus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 936, "text": "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in>150 eukaryote genomes. It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. We extended the Genomicus database originally dedicated to vertebrate to four new clades, including plants, non-vertebrate metazoa, protists and fungi. This visualization tool allows evolutionary phylogenomics analysis and exploration. Here, we describe the graphical modules of Genomicus and show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and study the evolution of a locus through homology relationships.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Genomicus update 2015: KaryoView and MatrixView provide a genome-wide perspective to multispecies comparative genomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1198, "text": "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides access to genomic information from extant species, as well as ancestral gene content and gene order for vertebrates and flowering plants. Here we present the new features available for vertebrate genome with a focus on new graphical tools. The interface to enter the database has been improved, two pairwise genome comparison tools are now available (KaryoView and MatrixView) and the multiple genome comparison tools (PhyloView and AlignView) propose three new kinds of representation and a more intuitive menu. These new developments have been implemented for Genomicus portal dedicated to vertebrates. This allows the analysis of 68 extant animal genomes, as well as 58 ancestral reconstructed genomes. The Genomicus server also provides access to ancestral gene orders, to facilitate evolutionary and comparative genomics studies, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Genomicus: five genome browsers for comparative genomics in eukaryota.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in >150 eukaryote genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in >150 eukaryote genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "abstract" } ] }, { "body": "Is amiodarone a class I anti-arrhythmic drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15989900", "http://www.ncbi.nlm.nih.gov/pubmed/20041841", "http://www.ncbi.nlm.nih.gov/pubmed/17352036", "http://www.ncbi.nlm.nih.gov/pubmed/21626366", "http://www.ncbi.nlm.nih.gov/pubmed/12491809", "http://www.ncbi.nlm.nih.gov/pubmed/11825323", "http://www.ncbi.nlm.nih.gov/pubmed/21728182" ], "ideal_answer": [ "Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile", "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone.", "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile.", "No. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile.", "Amiodarone, an iodinated benzofuran derivative, introduced in 1960 s as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970 s and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent. " ], "exact_answer": "no", "concepts": [ "http://www.biosemantics.org/jochem#4274241", "http://www.biosemantics.org/jochem#4075064" ], "type": "yesno", "id": "5509df4ac2af5d5b70000003", "snippets": [ { "offsetInBeginSection": 1185, "offsetInEndSection": 1374, "text": "Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21626366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11825323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 413, "text": "Amiodarone, an iodinated benzofuran derivative, introduced in 1960's as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970's and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20041841", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 655, "text": "Amiodarone, a representative class III agent, exerts negative dromotropism by suppressing the fast sodium current responsible for conduction in acute administration (class I effects). Chronic amiodarone causes prolongation of ERP (class III effects), which is sometimes associated with negative dromotropism based on the alteration of passive or active membrane properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12491809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Amiodarone, an iodinated benzofuran derivative with predominantly class III anti-arrhythmic effects, is used to treat supraventricular and ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21728182", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 411, "text": "Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20041841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Amiodarone, a class III antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17352036", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 412, "text": "Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20041841", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 316, "text": "Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11825323", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 236, "text": "Amiodarone is a potent class III anti-arrhythmic drug that also possesses beta-blocking properties", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15989900", "endSection": "abstract" } ] }, { "body": "Which is the prognostic meaning of delayed enhancement documented in patients hypertrophic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19477402", "http://www.ncbi.nlm.nih.gov/pubmed/19740409", "http://www.ncbi.nlm.nih.gov/pubmed/23376948", "http://www.ncbi.nlm.nih.gov/pubmed/22128204", "http://www.ncbi.nlm.nih.gov/pubmed/19784900", "http://www.ncbi.nlm.nih.gov/pubmed/20688032", "http://www.ncbi.nlm.nih.gov/pubmed/18204915", "http://www.ncbi.nlm.nih.gov/pubmed/22135401", "http://www.ncbi.nlm.nih.gov/pubmed/12224720", "http://www.ncbi.nlm.nih.gov/pubmed/19808288", "http://www.ncbi.nlm.nih.gov/pubmed/22498326", "http://www.ncbi.nlm.nih.gov/pubmed/22348519", "http://www.ncbi.nlm.nih.gov/pubmed/21234292", "http://www.ncbi.nlm.nih.gov/pubmed/15861263", "http://www.ncbi.nlm.nih.gov/pubmed/21498307", "http://www.ncbi.nlm.nih.gov/pubmed/20339815", "http://www.ncbi.nlm.nih.gov/pubmed/19474054", "http://www.ncbi.nlm.nih.gov/pubmed/22687593", "http://www.ncbi.nlm.nih.gov/pubmed/20079992", "http://www.ncbi.nlm.nih.gov/pubmed/20667520", "http://www.ncbi.nlm.nih.gov/pubmed/20102955", "http://www.ncbi.nlm.nih.gov/pubmed/18208827", "http://www.ncbi.nlm.nih.gov/pubmed/18562248", "http://www.ncbi.nlm.nih.gov/pubmed/22935464" ], "ideal_answer": [ "Delayed enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients, and is associated with cardiovascular mortality, heart failure death, and all-cause mortality in HCM." ], "exact_answer": [ "Delayed enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.disease-ontology.org/api/metadata/DOID:11984", "http://www.disease-ontology.org/api/metadata/DOID:11986", "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009682", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024741", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312" ], "type": "factoid", "id": "5339ecf4d6d3ac6a3400005f", "snippets": [ { "offsetInBeginSection": 1208, "offsetInEndSection": 1466, "text": " It is possible to conclude that there is a high prevalence of myocardial fibrosis in hypertrophic cardiomyopathy patients with high-risk or recovered from cardiac sudden death, like those with clinical indication to implantable cardioverter -defibrillator. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20339815", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1018, "text": "AF in HCM is related with myocardial fibrosis detected by DE-CMR and dilatation of the LA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20079992", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1388, "text": "Over the follow-up period, the annualized adverse cardiovascular event rate in patients with DE exceeded that in patients without DE but did not achieve statistical significance (5.5% versus 3.3%; P=0.5). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808288", "endSection": "abstract" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1780, "text": "Late gadolinium enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients. There are significant relationships between LGE and cardiovascular mortality, heart failure death, and all-cause mortality in HCM. Additionally, LGE and SCD/aborted SCD displayed a trend toward significance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22498326", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1364, "text": "The hyperenhanced apical myocardium had a lower percentage of systolic myocardial thickening, and was associated with serious symptoms (e.g. syncope) and ventricular arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498307", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1413, "text": "A semi-quantitative index of DCE is a significant multivariable predictor of both clinical VT/VF and of risk for SCD and may contribute to risk assessment in borderline or controversial cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19474054", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1509, "text": "Myocardial scar imaged by CE-CMR is common in patients with HCM, and is predictive of VT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18562248", "endSection": "abstract" } ] }, { "body": "What is the COUGER tool?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24861628" ], "ideal_answer": [ "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. ", "COUGER is a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. It takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. To achieve this task, COUGER uses a classification approach, with features that reflect the DNA-binding specificities of the putative co-factors. The identified co-factors are presented in a user-friendly output page, together with information that allows the user to understand and to explore the contributions of individual co-factor features." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984" ], "type": "summary", "id": "56ae35bc0a360a5e45000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "COUGER--co-factors associated with uniquely-bound genomic regions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "title" }, { "offsetInBeginSection": 576, "offsetInEndSection": 1374, "text": "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. To achieve this task, COUGER uses a classification approach, with features that reflect the DNA-binding specificities of the putative co-factors. The identified co-factors are presented in a user-friendly output page, together with information that allows the user to understand and to explore the contributions of individual co-factor features. COUGER can be run as a stand-alone tool or through a web interface: http://couger.oit.duke.edu.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 929, "text": "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1102, "text": "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 931, "text": "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 933, "text": "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 1079, "text": "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. To achieve this task, COUGER uses a classification approach, with features that reflect the DNA-binding specificities of the putative co-factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 933, "text": "Here, we present an interactive web implementation of COUGER, a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24861628", "endSection": "abstract" } ] }, { "body": "Are there drugs for Tick-borne Encephalitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24001228", "http://www.ncbi.nlm.nih.gov/pubmed/24076358", "http://www.ncbi.nlm.nih.gov/pubmed/23784447", "http://www.ncbi.nlm.nih.gov/pubmed/23697658", "http://www.ncbi.nlm.nih.gov/pubmed/22535622", "http://www.ncbi.nlm.nih.gov/pubmed/20656033", "http://www.ncbi.nlm.nih.gov/pubmed/23919605", "http://www.ncbi.nlm.nih.gov/pubmed/24035586", "http://www.ncbi.nlm.nih.gov/pubmed/23452322", "http://www.ncbi.nlm.nih.gov/pubmed/22727684", "http://www.ncbi.nlm.nih.gov/pubmed/22730949", "http://www.ncbi.nlm.nih.gov/pubmed/24096319", "http://www.ncbi.nlm.nih.gov/pubmed/24225644", "http://www.ncbi.nlm.nih.gov/pubmed/24256889", "http://www.ncbi.nlm.nih.gov/pubmed/23096037", "http://www.ncbi.nlm.nih.gov/pubmed/22984545", "http://www.ncbi.nlm.nih.gov/pubmed/24159517", "http://www.ncbi.nlm.nih.gov/pubmed/23377671", "http://www.ncbi.nlm.nih.gov/pubmed/23638205", "http://www.ncbi.nlm.nih.gov/pubmed/23259984" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050175", "o": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:993" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:993", "o": "Flavivirus infectious disease" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050175", "o": "tick-borne encephalitis" } ], "ideal_answer": [ "No drug therapy available today" ], "exact_answer": [ [ "No drug therapy available today" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004667", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060829", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004668", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004669", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017282", "http://www.disease-ontology.org/api/metadata/DOID:0050175", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004672", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004663", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004664", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004675", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018349" ], "type": "list", "id": "532083389b2d7acc7e000003", "snippets": [ { "offsetInBeginSection": 42, "offsetInEndSection": 321, "text": " tick-borne encephalitis (TBE) have been detected in Bulgaria. Considering the remarkable increase in TBE morbidity in Europe over the past two decades, we conducted a study of TBE among patients with acute viral meningitis who were hospitalised in Bulgaria during 2009 to 2012. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256889", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 913, "text": "Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24001228", "endSection": "abstract" } ] }, { "body": "Is SLC22A3 expressed in the brain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "http://www.ncbi.nlm.nih.gov/pubmed/21352605", "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "http://www.ncbi.nlm.nih.gov/pubmed/18513366", "http://www.ncbi.nlm.nih.gov/pubmed/19033200", "http://www.ncbi.nlm.nih.gov/pubmed/15028779", "http://www.ncbi.nlm.nih.gov/pubmed/19702534" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0091809", "o": "D009474" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0091286", "o": "D009474" } ], "ideal_answer": [ "Yes, SLC22A3 (organic cation transporter (OCT3)) is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054022", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001921" ], "type": "yesno", "id": "571e3d42bb137a4b0c000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1223, "text": "In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18513366", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1619, "text": "CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21352605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1441, "text": "CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21352605", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 205, "text": "Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1676, "text": "CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21352605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": " The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1441, "text": "CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21352605", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 302, "text": "Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 834, "text": "OCT2-OCT-3 display differential tissue distribution: OCT1 is predominantly found in liver of humans, and liver and kidney in rodents; OCT2 is most strongly expressed in both human and rodent kidney, whereas is OCT3 primarily expressed in placenta, but also more widely detected in various tissues, including brain and lung.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19702534", "endSection": "abstract" } ] }, { "body": "Has the protein TIEG1 been associated with apoptosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20691807", "http://www.ncbi.nlm.nih.gov/pubmed/23815903", "http://www.ncbi.nlm.nih.gov/pubmed/12065093", "http://www.ncbi.nlm.nih.gov/pubmed/12788480", "http://www.ncbi.nlm.nih.gov/pubmed/21524276", "http://www.ncbi.nlm.nih.gov/pubmed/21423731", "http://www.ncbi.nlm.nih.gov/pubmed/14743447", "http://www.ncbi.nlm.nih.gov/pubmed/22563190", "http://www.ncbi.nlm.nih.gov/pubmed/17659279", "http://www.ncbi.nlm.nih.gov/pubmed/10471833", "http://www.ncbi.nlm.nih.gov/pubmed/10573529", "http://www.ncbi.nlm.nih.gov/pubmed/17308981", "http://www.ncbi.nlm.nih.gov/pubmed/22349513", "http://www.ncbi.nlm.nih.gov/pubmed/18930345", "http://www.ncbi.nlm.nih.gov/pubmed/17951258", "http://www.ncbi.nlm.nih.gov/pubmed/22025675", "http://www.ncbi.nlm.nih.gov/pubmed/12771931", "http://www.ncbi.nlm.nih.gov/pubmed/20201061", "http://www.ncbi.nlm.nih.gov/pubmed/20945337", "http://www.ncbi.nlm.nih.gov/pubmed/18798273", "http://www.ncbi.nlm.nih.gov/pubmed/23244828", "http://www.ncbi.nlm.nih.gov/pubmed/17729309" ], "triples": 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"http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F303838373600E", "o": "Cpg20" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_4F303838373600B", "o": "TIEG-1" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_4F303838373600B", "o": "TGFB-inducible early growth response protein 1" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F303838373600E", "o": "Tieg1" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4F303838373600E", "o": "Klf10" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F303838373600C", "o": "Zinc finger transcription factor homolog CPG20" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F303838373600A", "o": "Krueppel-like factor 10" }, { "p": 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"http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8423440", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8428062", "o": "MeSH" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/O89091", "o": "http://linkedlifedata.com/resource/#_4F38393039310010" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_4F383930393100E", "o": "TGFB-inducible early growth response protein 1" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F38393039310010", "o": "Tieg" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F383930393100C", "o": "GDNF-inducible factor" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F383930393100D", "o": "Transcription factor GIF" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F38393039310010", "o": "Gdnfif" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F383930393100E", "o": "Transforming growth factor-beta-inducible early growth response protein 1" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_4F383930393100D", "o": "mGIF" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F383930393100B", "o": "Krueppel-like factor 10" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F38393039310010", "o": "Tieg1" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4F38393039310010", "o": "Klf10" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_4F383930393100E", "o": "TIEG-1" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1308314", "o": "http://linkedlifedata.com/resource/umls/id/C0012940" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0050767", "o": "DNA Binding Protein" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0404940", "o": "DNA binding protein" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17877761", "o": "DNA-Binding Proteins [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17974184", "o": "Binding Protein, DNA" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0050901", "o": "DNA-Binding Proteins" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0050769", "o": "DNA Binding Proteins" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1308314", "o": "http://linkedlifedata.com/resource/umls/id/C0040648" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0057942", "o": "Factors, Transcription" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17904335", "o": "Transcription Factors [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18024172", "o": "Factor, Transcription" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0127530", "o": "Transcription Factors" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1811857", "o": "transcription factors" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18048422", "o": "Transcription Factor" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1959548", "o": "TRANSCRIPTION FACTOR" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0490726", "o": "transcription factor" } ], "ideal_answer": [ "Yes, TIEG1 (also known as KLF10) seems to play a role in regulating apoptosis." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/KLF10_RAT", "http://www.uniprot.org/uniprot/KLF10_MOUSE", "http://www.uniprot.org/uniprot/KLF10_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017209" ], "type": "yesno", "id": "53386282d6d3ac6a3400005a", "snippets": [ { "offsetInBeginSection": 33, "offsetInEndSection": 215, "text": "TGF-beta) inducible early gene 1 (TIEG1) is known to induce apoptosis in TGF-beta sensitive pancreatic cancer cells, yet its effect on TGF-beta resistant cancer cells remains unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18930345", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1116, "text": "overexpression of TIEG1, protected ALL cells against chemotherapy-induced cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18798273", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1366, "text": " TIEG1 might be involved in mediating this effect from the microenvironment onto the leukemia cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18798273", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 813, "text": "We also demonstrate that TIEG-1 ectopic expression in CGNPs induces cell cycle arrest that can lead to apoptosis but fails to promote differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17951258", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 830, "text": "TIEG1 acts as an inducer or repressor of gene transcription to enhance the TGFbeta/Smad pathway, as well at other signaling pathways, to regulate cell proliferation, differentiation, and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17729309", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 98, "text": "TGFbeta inducible early gene (TIEG1) mimics TGFbeta action and induces apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17659279", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 514, "text": "the transforming growth factor-beta- (TGF-beta-) inducible early response 1 gene (TIEG1), which plays a pivotal role in TGF-beta-regulated cell growth control and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12788480", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1430, "text": "Induction of mRNA for Smad4 and the TGF-beta1-regulated apoptosis-inducing transcription factor TGF-beta1-inducible early gene (TIEG1) was detected within the first 6 h of doxazosin treatmen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12771931", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 316, "text": "TIEG1 (TGF-beta inducible early gene) is a recently characterized transcription factor regulated by TGF-beta that induces apoptosis when overexpressed in pancreatic adenocarcinoma cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12065093", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 32, "text": "Influence of TIEG1 on apoptosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815903", "endSection": "title" }, { "offsetInBeginSection": 36, "offsetInEndSection": 118, "text": "the influence of TIEG1 on apoptosis of HL-60 cells and the expression of Bcl-2/Bax", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815903", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1030, "text": "The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244828", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1512, "text": "the overexpression of TIEG1 mediated growth inhibition and apoptosis in TGF-\u03b21-resistant HCC cell lines,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22563190", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 421, "text": "On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22349513", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 58, "text": "LF10, transforming growth factor-\u03b2-inducible early gene 1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22349513", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 42, "text": "IEG1 can induce apoptosis of cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025675", "endSection": "abstract" }, { "offsetInBeginSection": 7, "offsetInEndSection": 108, "text": "TGF-\u03b2 inducible early gene 1) plays a significant role in regulating cell proliferation and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21524276", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 178, "text": "TIEG1) is a Kr\u00fcppel-like transcription factor (KLF10) that was originally cloned from human osteoblasts as an early response gene to TGF-\u03b2 treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21423731", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1412, "text": "Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1(-/-) cells reversed the RANKL-induced NFATc1 signaling defect in TIEG1(-/-) precursors and eliminated the differentiation and apoptosis defects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21423731", "endSection": "abstract" }, { "offsetInBeginSection": 31, "offsetInEndSection": 170, "text": "(TGF)-\u03b2 inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20945337", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 685, "text": "TIEG1 has been shown to mimic the effects of TGF-beta in various carcinoma cells and plays a critical role in the apoptotic cascade", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691807", "endSection": "abstract" }, { "offsetInBeginSection": 39, "offsetInEndSection": 181, "text": "(TIEG) is a family of primary response genes induced by TGF-beta, which are well recognized in regulating cellular proliferation and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20201061", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 492, "text": "In human and murine tissues it has been shown that TIEG1 and TIEG2 induce apoptosis and inhibit cell growth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17308981", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 550, "text": "overexpression of TIEG1 in OLI-neu cells induced apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14743447", "endSection": "abstract" }, { "offsetInBeginSection": 35, "offsetInEndSection": 215, "text": "(TGF-beta(1))-inducible transcription factors have recently elicited interest because of their critical role in the regulation of cell proliferation, differentiation, and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573529", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 502, "text": "ectopic overexpression of TIEG is sufficient to trigger the apoptotic cell program in these cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10471833", "endSection": "abstract" } ] }, { "body": "Which is the cellular localization of the protein Opa1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25579226", "http://www.ncbi.nlm.nih.gov/pubmed/19168126", "http://www.ncbi.nlm.nih.gov/pubmed/17709430", "http://www.ncbi.nlm.nih.gov/pubmed/22406748", "http://www.ncbi.nlm.nih.gov/pubmed/18281461", "http://www.ncbi.nlm.nih.gov/pubmed/22579715", "http://www.ncbi.nlm.nih.gov/pubmed/21983901", "http://www.ncbi.nlm.nih.gov/pubmed/16413305", "http://www.ncbi.nlm.nih.gov/pubmed/17545159", "http://www.ncbi.nlm.nih.gov/pubmed/11847212", "http://www.ncbi.nlm.nih.gov/pubmed/24282027", "http://www.ncbi.nlm.nih.gov/pubmed/20045077", "http://www.ncbi.nlm.nih.gov/pubmed/23663851", "http://www.ncbi.nlm.nih.gov/pubmed/20079867", "http://www.ncbi.nlm.nih.gov/pubmed/21980395", "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "http://www.ncbi.nlm.nih.gov/pubmed/16737747", "http://www.ncbi.nlm.nih.gov/pubmed/25112877", "http://www.ncbi.nlm.nih.gov/pubmed/14970223", "http://www.ncbi.nlm.nih.gov/pubmed/12123827", "http://www.ncbi.nlm.nih.gov/pubmed/24632637", "http://www.ncbi.nlm.nih.gov/pubmed/18074630", "http://www.ncbi.nlm.nih.gov/pubmed/25582749", "http://www.ncbi.nlm.nih.gov/pubmed/25847151", "http://www.ncbi.nlm.nih.gov/pubmed/20678484", "http://www.ncbi.nlm.nih.gov/pubmed/23906536", "http://www.ncbi.nlm.nih.gov/pubmed/24633199", "http://www.ncbi.nlm.nih.gov/pubmed/25744979", "http://www.ncbi.nlm.nih.gov/pubmed/25298396", "http://www.ncbi.nlm.nih.gov/pubmed/21459773", "http://www.ncbi.nlm.nih.gov/pubmed/11017079", "http://www.ncbi.nlm.nih.gov/pubmed/20652258", "http://www.ncbi.nlm.nih.gov/pubmed/21397211" ], "ideal_answer": [ "The Opa1 protein localizes to the mitochondria.", "Opa1 is found normally in the mitochondrial intermembrane space." ], "exact_answer": [ "mitochondrial intermembrane space" ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0070585" ], "type": "factoid", "id": "5717d64f29809bbe7a000001", "snippets": [ { "offsetInBeginSection": 302, "offsetInEndSection": 457, "text": ". The subcellular distribution of mOPA1 overexpressed in COS-7 cells largely overlapped that of endogenous cytochrome c, a well known mitochondrial marker,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11847212", "endSection": "abstract" }, { "offsetInBeginSection": 921, "offsetInEndSection": 990, "text": "elease of high MW Opa-1 isoforms from the mitochondria to the cytosol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24632637", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 861, "text": " mitochondrial fusion (opa-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23663851", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1037, "text": "mitochondrial fusion genes Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optic atrophy 1) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21459773", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 833, "text": "Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. Submitochondrial fractionation by sucrose density-gradient centrifugation shows that the 88-kDa protein predominantly associates with the mitochondrial outer membrane, on the contrary, the 93-kDa protein associates with the inner membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 575, "text": "We describe here a nuclear gene, OPA1, that maps within the candidate region and encodes a dynamin-related protein localized to mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11017079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space, where it facilitates fusion between mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17709430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17709430", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12123827", "endSection": "title" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1105, "text": "In addition to the capacity of these proteins to promote fusion, mitofusin 2 or OPA1 regulate mitochondrial metabolism and loss-of-function reduces oxygen consumption and the capacity to oxidize substrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20079867", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 380, "text": "Here, we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 924, "text": "Our experiments restrict the function of prohibitins to mitochondria and identify the processing of the dynamin-like GTPase OPA1, an essential component of the mitochondrial fusion machinery, as the central cellular process controlled by prohibitins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18281461", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1047, "text": "LRRK2 partially co-localizes with endosomal dynamin-1 or with mitofusins and OPA1 at mitochondrial membranes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282027", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 1280, "text": "While initial fusion of mitochondria by 15d-PGJ2 required the presence of both outer (Mfn1 and Mfn2) and inner (OPA1) mitochondrial membrane fusion proteins, later mitochondrial changes involved increased degradation of the fusion protein OPA1 and ubiquitination of newly synthesized OPA1 along with decreased expression of Mfn1 and Mfn2, which likely contributed to the loss of tubular rigidity, disorganization of cristae, and formation of large swollen degenerated dysfunctional mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20678484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Assay and properties of the mitochondrial dynamin related protein Opa1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16413305", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Mitochondrial remodeling following fission inhibition by 15d-PGJ2 involves molecular changes in mitochondrial fusion protein OPA1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20678484", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial Ca(2+) signaling and aldosterone production in H295R adrenocortical cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23906536", "endSection": "abstract" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1652, "text": "Our results define, for the first time, a function of the middle domain of the Opa1 protein and demonstrate that mitochondrial retention of Opa1 protein is essential for normal embryogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20652258", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 244, "text": "Here, we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space, where it facilitates fusion between mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17709430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545159", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21980395", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 807, "text": "Lack of mitochondrial retention of Opa1 is sufficient to cause the cellular Opa1 loss-of-function phenotype as the mitochondria are fragmented, indicating an inability to fuse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20652258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Opa1, also known as Mgm1 in yeast, is a mitochondrial member of the dynamin family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16413305", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 237, "text": "Unlike other dynamin family members, Opa1 has an N-terminal mitochondrial targeting sequence, suggesting that this protein is imported into mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16413305", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 521, "text": "Here, we describe biochemical techniques, such as mitochondrial isolation, digitonin extraction, a protease protection assay, and carbonate extraction, that were used to determine that mammalian Opa1 resides in the intermembrane space where it is tightly bound to the inner membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16413305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17709430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21980395", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 246, "text": "we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12504110", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 534, "text": "PKA phosphorylates perilipin, a protein localized on the surface of lipid droplets that serves as a gatekeeper to regulate access of lipases converting stored triglycerides to free fatty acids and glycerol in a phosphorylation-dependent manner. Here, we report a new function for optic atrophy 1 (OPA1), a protein known to regulate mitochondrial dynamics, as a dual-specificity A-kinase anchoring protein associated with lipid droplets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21983901", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 521, "text": "We find that Mgm1/OPA1 is localized to the mitochondrial intermembrane space,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14970223", "endSection": "abstract" } ] }, { "body": "Which are the drugs utilized for the burning mouth syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8725589", "http://www.ncbi.nlm.nih.gov/pubmed/12110042", "http://www.ncbi.nlm.nih.gov/pubmed/21223496", "http://www.ncbi.nlm.nih.gov/pubmed/1776404", "http://www.ncbi.nlm.nih.gov/pubmed/17287703", "http://www.ncbi.nlm.nih.gov/pubmed/22040716", "http://www.ncbi.nlm.nih.gov/pubmed/20690412", "http://www.ncbi.nlm.nih.gov/pubmed/12536654", "http://www.ncbi.nlm.nih.gov/pubmed/18625105", "http://www.ncbi.nlm.nih.gov/pubmed/14650993", "http://www.ncbi.nlm.nih.gov/pubmed/23772971", "http://www.ncbi.nlm.nih.gov/pubmed/23201368", "http://www.ncbi.nlm.nih.gov/pubmed/2726203", "http://www.ncbi.nlm.nih.gov/pubmed/14765022", "http://www.ncbi.nlm.nih.gov/pubmed/24558551", "http://www.ncbi.nlm.nih.gov/pubmed/11485137", "http://www.ncbi.nlm.nih.gov/pubmed/23229252", "http://www.ncbi.nlm.nih.gov/pubmed/1508523", "http://www.ncbi.nlm.nih.gov/pubmed/17541900", "http://www.ncbi.nlm.nih.gov/pubmed/19837207", "http://www.ncbi.nlm.nih.gov/pubmed/17559486", "http://www.ncbi.nlm.nih.gov/pubmed/22260804", "http://www.ncbi.nlm.nih.gov/pubmed/10625850", "http://www.ncbi.nlm.nih.gov/pubmed/9830647", "http://www.ncbi.nlm.nih.gov/pubmed/17849966", "http://www.ncbi.nlm.nih.gov/pubmed/20415927", "http://www.ncbi.nlm.nih.gov/pubmed/22092585", "http://www.ncbi.nlm.nih.gov/pubmed/15210564", "http://www.ncbi.nlm.nih.gov/pubmed/23429751", "http://www.ncbi.nlm.nih.gov/pubmed/18548844", "http://www.ncbi.nlm.nih.gov/pubmed/18588600", "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "http://www.ncbi.nlm.nih.gov/pubmed/18976257", "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "http://www.ncbi.nlm.nih.gov/pubmed/19450321", "http://www.ncbi.nlm.nih.gov/pubmed/22612823", "http://www.ncbi.nlm.nih.gov/pubmed/22669143", "http://www.ncbi.nlm.nih.gov/pubmed/2811814", "http://www.ncbi.nlm.nih.gov/pubmed/8543701", "http://www.ncbi.nlm.nih.gov/pubmed/18343329", "http://www.ncbi.nlm.nih.gov/pubmed/21743415", "http://www.ncbi.nlm.nih.gov/pubmed/21743413", "http://www.ncbi.nlm.nih.gov/pubmed/16903201", "http://www.ncbi.nlm.nih.gov/pubmed/22750263", "http://www.ncbi.nlm.nih.gov/pubmed/24164777", "http://www.ncbi.nlm.nih.gov/pubmed/11441716", "http://www.ncbi.nlm.nih.gov/pubmed/21528119", "http://www.ncbi.nlm.nih.gov/pubmed/14704612", "http://www.ncbi.nlm.nih.gov/pubmed/11838624", "http://www.ncbi.nlm.nih.gov/pubmed/22344742", "http://www.ncbi.nlm.nih.gov/pubmed/19658340", "http://www.ncbi.nlm.nih.gov/pubmed/22044166", "http://www.ncbi.nlm.nih.gov/pubmed/18558051", "http://www.ncbi.nlm.nih.gov/pubmed/1923398", "http://www.ncbi.nlm.nih.gov/pubmed/2098940", "http://www.ncbi.nlm.nih.gov/pubmed/19689438", "http://www.ncbi.nlm.nih.gov/pubmed/15195716", "http://www.ncbi.nlm.nih.gov/pubmed/22957483", "http://www.ncbi.nlm.nih.gov/pubmed/22819057", "http://www.ncbi.nlm.nih.gov/pubmed/10425973", "http://www.ncbi.nlm.nih.gov/pubmed/16637799", "http://www.ncbi.nlm.nih.gov/pubmed/20969436", "http://www.ncbi.nlm.nih.gov/pubmed/7629360", "http://www.ncbi.nlm.nih.gov/pubmed/20597947", "http://www.ncbi.nlm.nih.gov/pubmed/8323246", "http://www.ncbi.nlm.nih.gov/pubmed/9844361" ], "ideal_answer": [ "Dopaminergic drugs should be given in patients with BMS. \nCatuama reduces the symptoms of BMS and may be a novel therapeutic strategy for the treatment of this disease.\nCapsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS.\nTreatment with placebos produced a response that was 72% as large as the response to active drugs" ], "exact_answer": [ [ "Dopaminergig drugs" ], [ "Catuama" ], [ "Capsaicina" ], [ "Alpha-lipoic acid" ], [ "Clonazepam" ], [ "Placebo therapy" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002054", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009059", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ], "type": "list", "id": "531d7430267d7dd053000008", "snippets": [ { "offsetInBeginSection": 269, "offsetInEndSection": 379, "text": "On average, treatment with placebos produced a response that was 72% as large as the response to active drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24164777", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1228, "text": "The concomitant prescription of tongue protector and AV is effective for treating patients with BMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22957483", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1101, "text": "We suggest that a subset of patients with BMS may be a phenotypic variant of RLS and a trial of dopaminergic drugs should be given in patients with BMS who has a history suggestive of RLS or in a patient who do not show a response to usual therapies for BMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819057", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1003, "text": "The systemic administration of Catuama reduces the symptoms of BMS and may be a novel therapeutic strategy for the treatment of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22669143", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 894, "text": "Therapies that used capsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22092585", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1382, "text": "Topical clonazepam, which previous analyses of clinical evidence have shown to be the drug of choice for BMS, also proved to be the most cost-effective of the drugs analysed for this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22044166", "endSection": "abstract" } ] }, { "body": "Is PTEN involved in follicular thyroid carcinoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11297621", "http://www.ncbi.nlm.nih.gov/pubmed/16487009", "http://www.ncbi.nlm.nih.gov/pubmed/9790504", "http://www.ncbi.nlm.nih.gov/pubmed/18055323", "http://www.ncbi.nlm.nih.gov/pubmed/12203792", "http://www.ncbi.nlm.nih.gov/pubmed/21417916", "http://www.ncbi.nlm.nih.gov/pubmed/9832031" ], "ideal_answer": [ "The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3962", "http://www.uniprot.org/uniprot/PTEN_XENLA" ], "type": "yesno", "id": "55031650e9bde69634000026", "snippets": [ { "offsetInBeginSection": 986, "offsetInEndSection": 1221, "text": "Two of the 259 patients (0.8%), with both follicular thyroid carcinoma and macrocephaly, were found to carry a germline mutation in the PTEN gene. The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21417916", "endSection": "abstract" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1422, "text": "The frequency of germline pathogenic PTEN mutations in an unselected series of patients with DTC is relatively low, but it is enriched by considering follicular histology and macrocephaly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21417916", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 594, "text": "Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18055323", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1489, "text": "A single male with follicular thyroid carcinoma from one of these 64 (2%) CS-like families harboured a germline point mutation, c.209T-->C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9832031", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 595, "text": "Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18055323", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1437, "text": "The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12203792", "endSection": "abstract" }, { "offsetInBeginSection": 1499, "offsetInEndSection": 1656, "text": "These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16487009", "endSection": "abstract" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1215, "text": "Our findings suggest that the PTEN tumor suppressor gene is occasionally inactivated in sporadic follicular thyroid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9790504", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 471, "text": "Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-specificity phosphatase, have been found in up to 80% of patients with Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11297621", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 647, "text": "The most common neoplasms in Cowden disease patients arise in the breast, skin, and thyroid (follicular subtype)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9790504", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1436, "text": "The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12203792", "endSection": "abstract" } ] }, { "body": "Which genome browser database for DNA shape annotations is available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25326329" ], "ideal_answer": [ "The Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution." ], "exact_answer": [ "GBshape" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064878", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ], "type": "factoid", "id": "56c8f4615795f9a73e00001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "GBshape: a genome browser database for DNA shape annotations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 1353, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1078, "text": "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 788, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1077, "text": "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1354, "text": "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 789, "text": "Whereas higher-order effects, such as chromatin accessibility, cooperativity and cofactors, have been described, DNA shape recently gained attention as another feature that fine-tunes the DNA binding specificities of some transcription factor families. Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 1078, "text": "Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 857, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1078, "text": "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 789, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" } ] }, { "body": "What is known about clinical efficacy of ceftriaxone for treatment of amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19008722", "http://www.ncbi.nlm.nih.gov/pubmed/20638444", "http://www.ncbi.nlm.nih.gov/pubmed/15907788", "http://www.ncbi.nlm.nih.gov/pubmed/23613806", "http://www.ncbi.nlm.nih.gov/pubmed/15635412", "http://www.ncbi.nlm.nih.gov/pubmed/25297012", "http://www.ncbi.nlm.nih.gov/pubmed/21970974", "http://www.ncbi.nlm.nih.gov/pubmed/16723044", "http://www.ncbi.nlm.nih.gov/pubmed/18326497", "http://www.ncbi.nlm.nih.gov/pubmed/24771634", "http://www.ncbi.nlm.nih.gov/pubmed/19694903", "http://www.ncbi.nlm.nih.gov/pubmed/22680643", "http://www.ncbi.nlm.nih.gov/pubmed/19697382", "http://www.ncbi.nlm.nih.gov/pubmed/8161465", "http://www.ncbi.nlm.nih.gov/pubmed/16832072", "http://www.ncbi.nlm.nih.gov/pubmed/17212618" ], "ideal_answer": [ "There have been a few case reports to suggest that ceftriaxone can be effective for treatment of amyotrophic lateral sclerosis. However, other case reports did not report clinical benefit of ceftriaxone therapy for ALS. Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis a through increased expression and activity of the glutamate transporter, GLT1. Clinical trials investigating potential clinical benefits of ceftriaxone in ALS are ongoing." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:332", "http://www.biosemantics.org/jochem#4249031" ], "type": "summary", "id": "54fc97b86ad7dcbc12000002", "snippets": [ { "offsetInBeginSection": 1143, "offsetInEndSection": 1252, "text": "Importantly, ceftriaxone is currently in clinical trials for the treatment of amyotrophic lateral sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22680643", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 472, "text": "Ceftriaxone delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis through upregulation of astrocytic glutamate transporter expression (GLT-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21970974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "OBJECTIVES: Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613806", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1219, "text": "Thirty-four compounds (including riluzole, ceftriaxone, minocyclin, PBA, lithium, acetylcysteine) in human and mouse ALS trials and an additional set of 1040 FDA-approved compounds also showed no effect on SOD1 promoter activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20638444", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 422, "text": "Two of these patients received ceftriaxone for 1 month without clinical improvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19697382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "In amyotrophic lateral sclerosis, down-regulation of the astrocyte-specific glutamate excitatory amino acid transporter 2 is hypothesized to increase extracellular glutamate, thereby leading to excitotoxic motor neuron death. The antibiotic ceftriaxone was recently reported to induce excitatory amino acid transporter 2 and to prolong the survival of mutant superoxide dismutase 1 transgenic mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19694903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "OBJECTIVE: Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis and in an in-vitro model of neuronal ischaemia through increased expression and activity of the glutamate transporter, GLT1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19008722", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 703, "text": "Dysfunction of EAAT2 is implicated in acute and chronic neurological disorders, including stroke/ischemia, temporal lobe epilepsy, amyotrophic lateral sclerosis, Alzheimer disease, human immunodeficiency virus 1-associated dementia, and growth of malignant gliomas. Ceftriaxone, one of the beta-lactam antibiotics, is a stimulator of EAAT2 expression with neuroprotective effects in both in vitro and in vivo models based in part on its ability to inhibit neuronal cell death by glutamate excitotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18326497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Motor neuron disease recovery associated with IV ceftriaxone and anti-Babesia therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17212618", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "This report summarizes what we believe to be the first verifiable case of a significant and progressive motor neuron disease (MND) consistent with amyotrophic lateral sclerosis that resolved during treatment with i.v. ceftriaxone plus oral atovaquone and mefloquine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17212618", "endSection": "abstract" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1100, "text": "Other agents (ceftriaxone, minocycline, ONO-2506, and IGF-1 polypeptide) are already in phase III trials involving large numbers of patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16832072", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 974, "text": "Ongoing trials are exploring the value of antiglutamatergic agents, including the cephalosporin antibiotic ceftriaxone, as well as antioxidants, mitochondrial enhancers and anti-apoptotic drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16723044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Recently, Rothstein et al. reported that beta-lactam antibiotics, including penicillin and ceftriaxone, are potential therapeutic drugs to treat some neurological disorders, e.g., amyotrophic lateral sclerosis (ALS), by modulating the expression of glutamate transporter GLT1 via gene activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15907788", "endSection": "abstract" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1536, "text": "Ceftriaxone was neuroprotective in vitro when used in models of ischaemic injury and motor neuron degeneration, both based in part on glutamate toxicity. When used in an animal model of the fatal disease ALS, the drug delayed loss of neurons and muscle strength, and increased mouse survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15635412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "We describe two patients with lateral amyotrophic sclerosis who, after informed consent, received empirical treatment with intravenous cephtriaxone at a dose of 2 g/24 hours for three weeks, with no positive results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8161465", "endSection": "abstract" }, { "offsetInBeginSection": 2933, "offsetInEndSection": 3066, "text": "Despite promising stage 2 data, stage 3 of this trial of ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25297012", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1243, "text": " Importantly, ceftriaxone is currently in clinical trials for the treatment of amyotrophic lateral sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22680643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The cephalosporin antibiotic ceftriaxone was evaluated as a potential therapeutic agent for the treatment of amyotrophic lateral sclerosis (ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24771634", "endSection": "abstract" } ] }, { "body": "What is the relationship between TailorX and Oncotype?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18922117", "http://www.ncbi.nlm.nih.gov/pubmed/23411384", "http://www.ncbi.nlm.nih.gov/pubmed/20665886", "http://www.ncbi.nlm.nih.gov/pubmed/23643806", "http://www.ncbi.nlm.nih.gov/pubmed/25240289" ], "ideal_answer": [ "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone." ], "type": "summary", "id": "56ccae765795f9a73e000035", "snippets": [ { "offsetInBeginSection": 302, "offsetInEndSection": 494, "text": "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411384", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 551, "text": "A cohort study was undertaken, including consecutive patients with early node-negative, ER-positive breast cancer diagnosed between 2006 and May 2013, including a period of prospective clinical trial (Trial Assigning Individualised Options for Treatment (TAILORx)) recruitment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25240289", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 701, "text": "Data were collected regarding patient demographics, tumour clinico-pathological features, Oncotype DX use and recurrence score and chemotherapy use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25240289", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1167, "text": "Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25240289", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1028, "text": "479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25240289", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1429, "text": "To evaluate the ability to guide treatment decisions in the group with a mid-range recurrence score, the North American Cooperative Groups developed the Trial Assessing IndiviuaLized Options for Treatment for breast cancer, a randomized trial of chemotherapy followed by hormonal therapy versus hormonal therapy alone on invasive disease-free survival-ductal carcinoma in situ (IDFS-DCIS) survival in women with node-negative, estrogen-receptor-positive breast cancer with a recurrence score of 11-25.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18922117", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 546, "text": "One of these tests, Oncotype DXtrade mark, is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue, which allows physicians to predict subgroups of hormone-receptor-positive, node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18922117", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 600, "text": "We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23643806", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 492, "text": "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Prediction of Oncotype DX and TAILORx risk categories using histopathological and immunohistochemical markers by classification and regression tree (CART) analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23643806", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 602, "text": "Each patient is stratified into a risk category based on a recurrence score (RS) and the TAILORx trial is determining the benefit of chemotherapy for patients with mid-range RSs. We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23643806", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1136, "text": "479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial. Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25240289", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 402, "text": "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411384", "endSection": "abstract" } ] }, { "body": "Does strenuous physical activity affect thyroid hormone metabolism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3101339", "http://www.ncbi.nlm.nih.gov/pubmed/7198038", "http://www.ncbi.nlm.nih.gov/pubmed/8743723", "http://www.ncbi.nlm.nih.gov/pubmed/14637241", "http://www.ncbi.nlm.nih.gov/pubmed/16175495", "http://www.ncbi.nlm.nih.gov/pubmed/596247", "http://www.ncbi.nlm.nih.gov/pubmed/2807143", "http://www.ncbi.nlm.nih.gov/pubmed/8325717", "http://www.ncbi.nlm.nih.gov/pubmed/18057380" ], "ideal_answer": [ "YES" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.biosemantics.org/jochem#4250045", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.biosemantics.org/jochem#4275389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000609", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042404", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0030375", "http://www.uniprot.org/uniprot/THA_SALSA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042403", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0097066", "http://www.biosemantics.org/jochem#4275394", "http://www.biosemantics.org/jochem#4250044", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006590", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070460", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "yesno", "id": "51598b08d24251bc0500009f", "snippets": [ { "offsetInBeginSection": 1207, "offsetInEndSection": 1517, "text": "The results of the present study in a unique experimental human model of maximal exposure to altitude and physical exercise demonstrate that extreme HA and strenuous physical exercise are coupled with specific endocrine adaptations. These include increased activity of the GH/IGF-I axis and a low T(3) syndrome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18057380", "endSection": "sections.0" }, { "offsetInBeginSection": 373, "offsetInEndSection": 585, "text": "3,5,3'-triiodothyronine (T3) and T4 levels increase during strenuous exercise, and, at the end of the exercise bout, a decrease of T3 and T4 levels, with an increase in TSH during the following 4-5 days, is seen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14637241", "endSection": "sections.0" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1584, "text": "the obtained results indicate that in intense exercise, causing the rapid development of fatigue, rapid increases in serum levels of hormones of the pituitary-adrenocortical, pituitary-gonadal and pituitary-thyroid systems occur.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8743723", "endSection": "sections.0" }, { "offsetInBeginSection": 435, "offsetInEndSection": 616, "text": "Mean levels of fasting plasma estradiol, luteinizing hormone, follicle-stimulating hormone, free thyroxine and triiodothyronine were significantly lower in AR compared to ER and SE.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8325717", "endSection": "sections.0" }, { "offsetInBeginSection": 565, "offsetInEndSection": 856, "text": "Reductions in plasma T4, T3 and T3/T4 ratio are probably due to inhibition of T4 secretion and 5'-monodeiodination with possible conversion of T4 to reverse T3 (rT3). These processes may represent a mechanism for regulation of thyroid hormone metabolism during strenuous and extended flight.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2807143", "endSection": "sections.0" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1429, "text": "Strenuous endurance training seems to have minor changes on the function of the thyroid gland. Depressed T4 levels in runners may rather be due to lowered TBG levels than due to direct effect of training.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3101339", "endSection": "sections.0" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1410, "text": "brief strenuous swimming or moderate bicycle exercise had minor or no effect on thyroid hormone concentrations when consideration was given to the attendant hemoconcentration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7198038", "endSection": "sections.0" }, { "offsetInBeginSection": 17, "offsetInEndSection": 154, "text": "thyroxine were determined in 26 men participating in a 90-km cross-country ski race, before, immediately after, and on the following days", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/596247", "endSection": "sections.0" }, { "offsetInBeginSection": 643, "offsetInEndSection": 823, "text": "Total thyroxine and free thyroxine in serum were significantly increased at the end of the race, but had returned to the pre-raced levels during the rest of the observation period.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/596247", "endSection": "sections.0" }, { "offsetInBeginSection": 124, "offsetInEndSection": 360, "text": "There are controversial results concerning thyroid hormone metabolism during strenuous exercise in adult athletes and only scant data concerning the impact of strenuous exercise on thyroid hormone metabolism in children and adolescents.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16175495", "endSection": "sections.0" } ] }, { "body": "Which is the main function of \"RNA sponges\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "http://www.ncbi.nlm.nih.gov/pubmed/25580223", "http://www.ncbi.nlm.nih.gov/pubmed/25630703", "http://www.ncbi.nlm.nih.gov/pubmed/25957803", "http://www.ncbi.nlm.nih.gov/pubmed/23615404", "http://www.ncbi.nlm.nih.gov/pubmed/25483404", "http://www.ncbi.nlm.nih.gov/pubmed/25404635" ], "ideal_answer": [ "Natural RNA circles function as efficient microRNA sponges. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants.", "Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. Natural RNA sponges sequestering cellular noncoding RNA molecules have been found in diverse organisms. In this issue, Lalaouna et al. (2015) report another type of RNA sponge, showing that stable intermediates of bacterial tRNA processing control endogenous small RNAs. Furthermore, survival analysis suggests that high OCT4-pg4 level is significantly correlated with poor prognosis of HCC patients." ], "type": "summary", "id": "56f112932ac5ed145900000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23615404", "endSection": "title" }, { "offsetInBeginSection": 675, "offsetInEndSection": 818, "text": "Mechanistic analysis revealed that OCT4-pg4 functions as a natural micro RNA sponge to protect OCT4 transcript from being inhibited by miR-145.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23615404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Natural RNA circles function as efficient microRNA sponges", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "endSection": "title" }, { "offsetInBeginSection": 179, "offsetInEndSection": 357, "text": "Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 579, "text": "Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1308, "text": "We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Natural RNA sponges sequestering cellular noncoding RNA molecules have been found in diverse organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25957803", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 270, "text": "n this issue, Lalaouna et al. (2015) report another type of RNA sponge, showing that stable intermediates of bacterial tRNA processing control endogenous small RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25957803", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 791, "text": "Circular RNAs can function as templates for viroid and viral replication, as intermediates in RNA processing reactions, as regulators of transcription in cis, as snoRNAs, and as miRNA sponges", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404635", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 757, "text": "Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 627, "text": "This can involve RNA sponges that sequester regulatory RNAs of mRNAs in the same regulon, but the underlying molecular mechanism of such mRNA cross talk remains little understood. Here, we report sponge-mediated mRNA cross talk in the posttranscriptional network of GcvB, a conserved Hfq-dependent small RNA with one of the largest regulons known in bacteria. We show that mRNA decay from the gltIJKL locus encoding an amino acid ABC transporter generates a stable fragment (SroC) that base-pairs with GcvB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25630703", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 303, "text": "the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25580223", "endSection": "abstract" } ] }, { "body": "Is the gene MAOA epigenetically modified by methylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22948232", "http://www.ncbi.nlm.nih.gov/pubmed/20505345", "http://www.ncbi.nlm.nih.gov/pubmed/22198720", "http://www.ncbi.nlm.nih.gov/pubmed/16893905", "http://www.ncbi.nlm.nih.gov/pubmed/22436428", "http://www.ncbi.nlm.nih.gov/pubmed/22139575", "http://www.ncbi.nlm.nih.gov/pubmed/22906985", "http://www.ncbi.nlm.nih.gov/pubmed/19777560", "http://www.ncbi.nlm.nih.gov/pubmed/18454435", "http://www.ncbi.nlm.nih.gov/pubmed/23116433", "http://www.ncbi.nlm.nih.gov/pubmed/20421737" ], "ideal_answer": [ "In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus.\nWe conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032259", "http://www.uniprot.org/uniprot/AOFA_CANFA", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006306", "http://www.uniprot.org/uniprot/AOFA_PONAB", "http://www.uniprot.org/uniprot/AOFA_SHEEP", "http://www.uniprot.org/uniprot/AOFA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175" ], "type": "yesno", "id": "56cf50253975bb303a00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22948232", "endSection": "title" }, { "offsetInBeginSection": 765, "offsetInEndSection": 888, "text": "We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22948232", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 349, "text": "In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22436428", "endSection": "abstract" }, { "offsetInBeginSection": 1251, "offsetInEndSection": 1468, "text": " The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22436428", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1148, "text": "The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116433", "endSection": "title" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1601, "text": "Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Effects of MAOA promoter methylation on susceptibility to paranoid schizophrenia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22198720", "endSection": "title" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1454, "text": "In conclusion, abnormalities of DNA methylation at the MAOA promoter may be associated with schizophrenia in males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22198720", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 383, "text": "In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22139575", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1720, "text": "Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22139575", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1174, "text": "We conclude that smoking reliably decreases MAOA methylation, but exact characterization of effects on level of methylation depend on genotype, smoking history, current smoking status, gender, and region of the promoter-associated CpG Island examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777560", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 742, "text": "Given that DNA methylation is linked to the regulation of gene expression, we hypothesized that epigenetic mechanisms factor into the MAOA expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20421737", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1489, "text": " the extended MAOA regulatory region contains two CpG islands (CGIs), one of which overlaps with the canonical MAOA promoter and the other is located further upstream; both CGIs exhibit sensitivity to differential methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20421737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Identification and characterization of putative methylation targets in the MAOA locus using bioinformatic approaches.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20421737", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20505345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "MAOA methylation is associated with nicotine and alcohol dependence in women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454435", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454435", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1266, "text": "We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454435", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 729, "text": "Analysis of CpG methylation in the MAOA promoter region revealed substantial methylation in females but not in males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893905", "endSection": "abstract" }, { "offsetInBeginSection": 1371, "offsetInEndSection": 1519, "text": "Therefore, allelic mRNA expression is affected by genetic and epigenetic events, both with the potential to modulate biogenic amine tone in the CNS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893905", "endSection": "abstract" } ] }, { "body": "Which mutations of phopspholamban have been found in patients with cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "http://www.ncbi.nlm.nih.gov/pubmed/22707725", "http://www.ncbi.nlm.nih.gov/pubmed/23871674", "http://www.ncbi.nlm.nih.gov/pubmed/21282613", "http://www.ncbi.nlm.nih.gov/pubmed/23568436", "http://www.ncbi.nlm.nih.gov/pubmed/12639993", "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "http://www.ncbi.nlm.nih.gov/pubmed/21332051", "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "http://www.ncbi.nlm.nih.gov/pubmed/16829191" ], "ideal_answer": [ "PLN mutation R14del [or c.40_42delAGA(p.Arg14del)] was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. Another PLN mutation is a T116G point mutation, substituting a termination codon for Leu-39 (L39stop), and it was identified in two families with hereditary heart failure. Hereditary mutants of phospholamban, such as Arg(9) to Cys, Arg(9) to Leu, Arg(9) to His, cause lethal, hereditary dilated cardiomyopathy.in specific, two patients presented a G-T missense mutation at the G26 nucleotide, which encodes an Arg-Leu substitution at codon 9 (R9L).One patient presented a G-A missense mutation at the same nucleotide, which encodes an Arg-His substitution at codon 9 (R9H). A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death." ], "exact_answer": [ [ "c.40_42delAGA(p.Arg14del)", "PLN R14 del" ], [ "PLN L39stop", "PLN R39X" ], [ "Arg(9) to Cys", "R9C" ], [ "Arg(9) to Leu", "R9L" ], [ "Arg(9) to His", "R9H" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.disease-ontology.org/api/metadata/DOID:0050700" ], "type": "list", "id": "5523f1a62c8b63434a000002", "snippets": [ { "offsetInBeginSection": 741, "offsetInEndSection": 1147, "text": " In 19 of 142 patients (13%), the PLN founder mutation c.40_42delAGA (p.Arg14del) was identified. PLN mutation carriers more often had low-voltage electrocardiograms (p\u00a0= 0.004), inverted T waves in leads V4 to V6 (p <0.001), and additional structural (p\u00a0= 0.007) or functional (p\u00a0= 0.017) left ventricular impairment, whereas desmosomal mutation carriers had more solitary right ventricular abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23871674", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 217, "text": "Recently, we showed that the c.40_42delAGA (p.Arg14del) mutation in the phospholamban (PLN) gene can be identified in 10-15\u00a0% of Dutch patients with dilated cardiomyopathy or arrhythmogenic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23568436", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 450, "text": "PLN mutation R14del was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1656, "text": "The PLN R14del founder mutation is present in a substantial number of patients clinically diagnosed with DCM or ARVC. R14del+ patients diagnosed with DCM showed an arrhythmogenic phenotype, and SCD at young age can be the presenting symptom. These findings support the concept of 'arrhythmogenic cardiomyopathy'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 1328, "text": "Herein we reveal mechanistic insight into how four hereditary mutants of phospholamban, Arg(9) to Cys, Arg(9) to Leu, Arg(9) to His, and Arg(14) deletion, alter regulation of SERCA. Deletion of Arg(14) disrupts the protein kinase A recognition motif, which abrogates phospholamban phosphorylation and results in constitutive SERCA inhibition. Mutation of Arg(9) causes more complex changes in function, where hydrophobic substitutions such as cysteine and leucine eliminate both SERCA inhibition and phospholamban phosphorylation, whereas an aromatic substitution such as histidine selectively disrupts phosphorylation. We demonstrate that the role of Arg(9) in phospholamban function is multifaceted: it is important for inhibition of SERCA, it increases the efficiency of phosphorylation, and it is critical for protein kinase A recognition in the context of the phospholamban pentamer. Given the synergistic consequences on contractility, it is not surprising that the mutants cause lethal, hereditary dilated cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707725", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 443, "text": "Phospholamban (PLN) is a key regulator of SR and cardiac function, and PLN mutations in humans have been associated with dilated cardiomyopathy (DCM). We previously reported the deletion of the highly conserved amino acid residue arginine 14 (nucleic acids 39, 40 and 41) in DCM patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 682, "text": "To assess the function of this mutant PLN, we introduced the PLN-R14Del in cardiac myocytes of the PLN null mouse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "endSection": "abstract" }, { "offsetInBeginSection": 1801, "offsetInEndSection": 1945, "text": "Thus, human PLN-R14Del is misrouted to the sarcolemma, in the absence of endogenous PLN, and alters NKA activity, leading to cardiac remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 337, "text": "Mutations in the gene encoding PLN have been associated with idiopathic dilated cardiomyopathy; however, no systematic search for PLN mutations in heart failure has been conducted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 892, "text": "Two patients presented a G-T missense mutation at the G26 nucleotide, which encodes an Arg-Leu substitution at codon 9 (R9L).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1158, "text": "One patient presented a G-A missense mutation at the same nucleotide, which encodes an Arg-His substitution at codon 9 (R9H). The fourth affected patient presented a T-G nonsense mutation at the nucleotide 116, substituting a termination codon for Leu-39 (L39stop).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 867, "text": "The genetic analysis was focused on R9C mutation with the ability to block PLN phosphorylation leading to chronic inhibition of SERCA2a activity. Another analysed mutation causing the alteration of PLN level in cells was related to the substitution of a leucine residue at position 39 with a premature stop codon (L39X). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21332051", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 295, "text": "A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282613", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 746, "text": "These effects are enhanced under oxidizing conditions, suggesting that oxidative stress may exacerbate the cardiotoxic effects of the PLN(R9C) mutant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282613", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 950, "text": "We identified 1 family with a deletion of arginine 14 in the PLN. Interestingly, unlike other individuals reported with the identical PLN mutation, these individuals were not diagnosed with dilated cardiomyopathy until their seventh decade when they were only mildly symptomatic with congestive heart failure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Phospholamban R14 deletion results in late-onset, mild, hereditary dilated cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "endSection": "title" }, { "offsetInBeginSection": 223, "offsetInEndSection": 689, "text": "Through genetic screening of dilated cardiomyopathy patients, we identified a previously uncharacterized deletion of arginine 14 (PLN-R14Del) in the coding region of the phospholamban (PLN) gene in a large family with hereditary heart failure. No homozygous individuals were identified. By middle age, heterozygous individuals developed left ventricular dilation, contractile dysfunction, and episodic ventricular arrhythmias, with overt heart failure in some cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 847, "text": "Transgenic mice overexpressing the mutant PLN-R14Del recapitulated human cardiomyopathy exhibiting similar histopathologic abnormalities and premature death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "endSection": "title" }, { "offsetInBeginSection": 370, "offsetInEndSection": 769, "text": "Here, a T116G point mutation, substituting a termination codon for Leu-39 (L39stop), was identified in two families with hereditary heart failure. The heterozygous individuals exhibited hypertrophy without diminished contractile performance. Strikingly, both individuals homozygous for L39stop developed dilated cardiomyopathy and heart failure, requiring cardiac transplantation at ages 16 and 27. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12639993", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 878, "text": "Here we report that an inherited human dilated cardiomyopathy with refractory congestive heart failure is caused by a dominant Arg --> Cys missense mutation at residue 9 (R9C) in phospholamban (PLN), a transmembrane phosphoprotein that inhibits the cardiac sarcoplasmic reticular Ca2+-adenosine triphosphatase (SERCA2a) pump. Transgenic PLN(R9C) mice recapitulated human heart failure with premature death. Cellular and biochemical studies revealed that, unlike wild-type PLN, PLN(R9C) did not directly inhibit SERCA2a. Rather, PLN(R9C) trapped protein kinase A (PKA), which blocked PKA-mediated phosphorylation of wild-type PLN and in turn delayed decay of calcium transients in myocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "endSection": "title" }, { "offsetInBeginSection": 704, "offsetInEndSection": 813, "text": "The PLN -42 C>G mutation was found in one patient with late onset familial apical hypertrophic cardiomyopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16829191", "endSection": "abstract" } ] }, { "body": "Which are the supplemental antioxidant in athletes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24323888", "http://www.ncbi.nlm.nih.gov/pubmed/21830999", "http://www.ncbi.nlm.nih.gov/pubmed/19089749", "http://www.ncbi.nlm.nih.gov/pubmed/23980734", "http://www.ncbi.nlm.nih.gov/pubmed/22828460", "http://www.ncbi.nlm.nih.gov/pubmed/23349254", "http://www.ncbi.nlm.nih.gov/pubmed/21116022", "http://www.ncbi.nlm.nih.gov/pubmed/23717772", "http://www.ncbi.nlm.nih.gov/pubmed/22212240", "http://www.ncbi.nlm.nih.gov/pubmed/21813916", "http://www.ncbi.nlm.nih.gov/pubmed/23600891", "http://www.ncbi.nlm.nih.gov/pubmed/21990004", "http://www.ncbi.nlm.nih.gov/pubmed/20308973", "http://www.ncbi.nlm.nih.gov/pubmed/21400082", "http://www.ncbi.nlm.nih.gov/pubmed/19597720", "http://www.ncbi.nlm.nih.gov/pubmed/23436649", "http://www.ncbi.nlm.nih.gov/pubmed/22080314", "http://www.ncbi.nlm.nih.gov/pubmed/23717765", "http://www.ncbi.nlm.nih.gov/pubmed/23800565", "http://www.ncbi.nlm.nih.gov/pubmed/18562771", "http://www.ncbi.nlm.nih.gov/pubmed/19838998", "http://www.ncbi.nlm.nih.gov/pubmed/16575496" ], "ideal_answer": [ "There are several antioxidant supplements belonging to different families, i.e. Vitamins, Polyphenols, alpha-lipoic acid, ubiquinones, n-3- polyunsaturated acids (PUFAs), minerals and others. Nonetheless the widespread use of these supplements, it is still debated their true usefulness, and it is not unanimously advised their use in athletes." ], "exact_answer": [ [ "Resveratrol" ], [ "Quercetin" ], [ "Vitamin C" ], [ "Biostimine" ], [ "Astaxanthin" ], [ "Melatonin" ], [ "coenzyme Q(10)" ], [ "Creatine" ], [ "Isoquercetin" ], [ "Epigallocatechin gallate" ], [ "n-3 fatty acids" ], [ "L. rhamnosus IMC 501" ], [ "L. paracasei IMC 502" ], [ "docosahexanoic acid (DHA)" ], [ "eicosapentanoic acid (EPA)" ], [ "Rhodiola Rosea" ], [ "Vitamin E" ], [ "Zinc" ], [ "whey and/or soy proteins" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000975", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019587", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ], "type": "list", "id": "52df8ce798d023950500000d", "snippets": [ { "offsetInBeginSection": 1138, "offsetInEndSection": 1515, "text": "Although these supplementations are increasingly used by master athletes, very few data are available on their effects on oxidative stress, muscle recovery, and physical performance. The potential benefits of supplement use in athletes are thus questionable. Some studies indicate no benefits, while others highlight potential negative side effects of vitamin supplementation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24323888", "endSection": "abstract" }, { "offsetInBeginSection": 1525, "offsetInEndSection": 1683, "text": "These data indicate that RQ significantly reduces exercise-induced lipid peroxidation without associated changes in inflammation or plasma antioxidant status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23980734", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1700, "text": "Cr supplementation inhibited the increase of inflammation markers TNF-\u03b1 and CRP, but not oxidative stress markers, due to acute exercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23800565", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1538, "text": "Quercetin and vitamin C supplementation may not be beneficial in lipid profile improvement, although it may reduce induce muscle damage and body fat percent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23717772", "endSection": "abstract" }, { "offsetInBeginSection": 1321, "offsetInEndSection": 1413, "text": "Vitamins C and E supplementation had no significant effect on any of the studied parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23717765", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1367, "text": "Effects of the two treatments relative to placebo on mean performance in the incremental test and time trial were unclear, but runners faster by 1 SD of peak speed demonstrated a possible improvement on peak running speed with BC juice (1.9%; \u00b12.5%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23600891", "endSection": "abstract" }, { "offsetInBeginSection": 1722, "offsetInEndSection": 1801, "text": "Training status correlates more strongly with antioxidant status than diet does", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23436649", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1714, "text": "Consequently, we can conclude that Biostimine supplementation reduces the postexercise level of TBARS by increasing the antioxidant activity of plasma but has no effect on inflammatory markers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349254", "endSection": "abstract" }, { "offsetInBeginSection": 2215, "offsetInEndSection": 2370, "text": "Supplementation with Asx could prevent exercise induced free radical production and depletion of non-enzymatic antioxidant defense in young soccer players.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828460", "endSection": "abstract" }, { "offsetInBeginSection": 1536, "offsetInEndSection": 1744, "text": "In conclusion these results indicated that treatment with melatonin in acute sports exercise reversed oxidative stress, improved defenses and lipid metabolism, which would result in an improvement in fitness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22212240", "endSection": "abstract" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 1534, "text": "CoQ(10) supplementation before strenuous exercise decreases the oxidative stress and modulates the inflammatory signaling, reducing the subsequent muscle damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21990004", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 648, "text": "Heretofore, Cr's positive therapeutic benefits in various oxidative stress-associated diseases have been reported in the literature and, recently, Cr has also been shown to exert direct antioxidant effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080314", "endSection": "abstract" }, { "offsetInBeginSection": 1932, "offsetInEndSection": 2062, "text": "These results indicate that Cr supplementation reduced oxidative DNA damage and lipid peroxidation induced by a single bout of RE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080314", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1584, "text": "Nevertheless, based upon the growing evidence that many athletic populations are vitamin D deficient or insufficient, it is recommended that athletes monitor their serum vitamin D concentration and consult with their health care professional and/or nutritionist to determine if they would derive health benefits from vitamin D supplementation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21830999", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 396, "text": "This study examined the effects of 1,000 mg quercetin + 1,000 mg vitamin C (QC); 1,000 mg quercetin, 1,000 mg vitamin C, 400 mg isoquercetin, 30 mg epigallocatechin gallate, and 400 mg n-3 fatty acids (QFO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813916", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1387, "text": "The two strains, L. rhamnosus IMC 501(\u00ae) and L. paracasei IMC 502(\u00ae), exert strong antioxidant activity. Athletes and all those exposed to oxidative stress may benefit from the ability of these probiotics to increase antioxidant levels and neutralize the effects of reactive oxygen species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21400082", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1791, "text": "These results indicate that supplementation with n-3 LCPUFAs significantly increased oxidative stress at rest and after a judo-training session.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21116022", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 207, "text": "Rhodiola Rosea, is an adaptogen plant which has been reported to promote fatty acids utilisation, to ameliorate antioxidant function, and to improve body resistance to physical strenuous efforts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20308973", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 390, "text": "Supplementation with antioxidant vitamin E to athletes at 267 mg (400 IUs) or greater has been reported to reduce levels of LP associated with exercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19838998", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1756, "text": "Results obtained at the end of the study indicate that zinc supplementation prevents production of free radicals by activating the antioxidant system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19597720", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1586, "text": "The significant increase in the UI of erythrocyte membranes indicates the potential for harm, because a high intake of PUFA might increase susceptibility to lipid peroxidation not counterbalanced by a higher increase in TAA. Adherence to the Mediterranean diet seems to be the better choice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18562771", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 248, "text": "A number of clinical trials have successfully been performed using whey and/or soy proteins in the treatment of many diseases. They both have antioxidant properties, which appears to be a factor in aerobic physical performance as well. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575496", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1733, "text": "The antioxidant effect of the two proteins is based on different mechanisms of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575496", "endSection": "abstract" } ] }, { "body": "Is glycyl-tRNA synthetase gene involved in the development of Charcot-Marie-Tooth disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17035524", "http://www.ncbi.nlm.nih.gov/pubmed/25420567", "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "http://www.ncbi.nlm.nih.gov/pubmed/12690580", "http://www.ncbi.nlm.nih.gov/pubmed/24669931", "http://www.ncbi.nlm.nih.gov/pubmed/24368416", "http://www.ncbi.nlm.nih.gov/pubmed/25168514", "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "http://www.ncbi.nlm.nih.gov/pubmed/23279345", "http://www.ncbi.nlm.nih.gov/pubmed/19470612", "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "http://www.ncbi.nlm.nih.gov/pubmed/24898252", "http://www.ncbi.nlm.nih.gov/pubmed/23990368" ], "ideal_answer": [ "Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration.", "Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D" ], "exact_answer": "yes", "type": "yesno", "id": "5713c4a11174fb1755000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25168514", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 375, "text": "Dominant mutations in GARS cause rare forms of Charcot-Marie-Tooth disease and distal spinal muscular atrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669931", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 809, "text": "Using exome sequencing she was found to harbor compound heterozygous mutations within the glycyl-tRNA synthetase (GARS) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669931", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 428, "text": "mutations of human GlyRS (hGlyRS) were also found to be associated with Charcot-Marie-Tooth disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24898252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24368416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25420567", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 957, "text": "Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25420567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12690580", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "[A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25420567", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279345", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 553, "text": "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 605, "text": "Here, we report the identification of four disease-associated missense mutations in the glycyl tRNA synthetase gene in families with CMT2D and dSMA-V.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12690580", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 305, "text": "Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25168514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "endSection": "title" }, { "offsetInBeginSection": 90, "offsetInEndSection": 321, "text": "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25420567", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 243, "text": "Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25168514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19470612", "endSection": "title" }, { "offsetInBeginSection": 194, "offsetInEndSection": 314, "text": "We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24368416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": " Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). In addition to GARS, mutations in three other tRNA synthetase genes cause similar neuropathies, although the underlying mechanisms are not fully understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 255, "text": "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": " Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25168514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12690580", "endSection": "title" }, { "offsetInBeginSection": 91, "offsetInEndSection": 323, "text": "These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25420567", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279345", "endSection": "abstract" } ] }, { "body": "Is there any software for automated analysis of FISH images?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21310746", "http://www.ncbi.nlm.nih.gov/pubmed/22665392", "http://www.ncbi.nlm.nih.gov/pubmed/21656271", "http://www.ncbi.nlm.nih.gov/pubmed/16749443", "http://www.ncbi.nlm.nih.gov/pubmed/17889539", "http://www.ncbi.nlm.nih.gov/pubmed/23903043", "http://www.ncbi.nlm.nih.gov/pubmed/15887538", "http://www.ncbi.nlm.nih.gov/pubmed/17674627", "http://www.ncbi.nlm.nih.gov/pubmed/22935778", "http://www.ncbi.nlm.nih.gov/pubmed/22163442", "http://www.ncbi.nlm.nih.gov/pubmed/20639591", "http://www.ncbi.nlm.nih.gov/pubmed/15351517", "http://www.ncbi.nlm.nih.gov/pubmed/11818019", "http://www.ncbi.nlm.nih.gov/pubmed/24240725", "http://www.ncbi.nlm.nih.gov/pubmed/20966547" ], "ideal_answer": [ "FISH is a popular molecular cytogenetic method. The output of a single FISH analysis is a set of several tens or hundreds microscopic images \u2014 a single evaluated sample is of roughly 20mm diameter. The goal of an automated evaluation is to replace the subjective evaluation of images by the laboratory technician to achieve higher uniformity of results. Following explanation of the principle of the method and the typical contents of images, the processing flow of image segmentation is outlined and the results are presented on several example images. Based on results there are software for automated analysis of FISH images." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007091", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984" ], "type": "yesno", "id": "5311cdcce3eabad021000007", "snippets": [ { "offsetInBeginSection": 1622, "offsetInEndSection": 1770, "text": "he study demonstrated the feasibility of automated FISH signal analysis that applying a CAD scheme to the automated generated 2-D projection images.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22935778", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 1485, "text": "A color imaging technique, multiplex fluorescent in situ hybridization (M-FISH), has been developed to ease the analysis of the process. Using an M-FISH technique each chromosome class (1,2, \u2026,22,X,Y) is stained with a unique color. However, significant variations between images are observed due to a number of factors such as uneven hybridization and spectral overlap among channels. These types of variations influence the pixel classification accuracy of image classification methods which are supervised and require a set of annotated images for training. In this paper, we present a fully unsupervised M-FISH chromosome image classification methodology. Our main contributions are 1) the assumption that the intensity of a chromosome pixel is sampled from multiple Gaussian components [Gaussian mixture model (GMM)] such that each component corresponds to one chromosome class, and 2) the initialization of the GMM model using the emission information of each chromosome class. This is feasible since prior to the M-FISH image acquirement, we already know which chromosome class is emitting to each of the five M-FISH image channels. The method has been tested on a large number of M-FISH images and an overall accuracy of 89.85% is reported. Our method is unsupervised and presents higher classification accuracy even when it is compared with common supervised based methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240725", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 1620, "text": "hybridization (FISH) tests provide promising molecular imaging biomarkers to more accurately and reliably detect and diagnose cancers and genetic disorders. Since current manual FISH signal analysis is low-efficient and inconsistent, which limits its clinical utility, developing automated FISH image scanning systems and computer-aided detection (CAD) schemes has been attracting research interests. To acquire high-resolution FISH images in a multi-spectral scanning mode, a huge amount of image data with the stack of the multiple three-dimensional (3-D) image slices is generated from a single specimen. Automated preprocessing these scanned images to eliminate the non-useful and redundant data is important to make the automated FISH tests acceptable in clinical applications. In this study, a dual-detector fluorescence image scanning system was applied to scan four specimen slides with FISH-probed chromosome X. A CAD scheme was developed to detect analyzable interphase cells and map the multiple imaging slices recorded FISH-probed signals into the 2-D projection images. CAD scheme was then applied to each projection image to detect analyzable interphase cells using an adaptive multiple-threshold algorithm, identify FISH-probed signals using a top-hat transform, and compute the ratios between the normal and abnormal cells. To assess CAD performance, the FISH-probed signals were also independently visually detected by an observer. The Kappa coefficients for agreement between CAD and observer ranged from 0.69 to 1.0 in detecting/counting FISH signal spots in four testing samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22935778", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 1185, "text": " In this paper we developed a sparse representation-based classification (SRC) algorithm based on L1-norm minimization for classifying chromosomes from multicolor fluorescence in situ hybridization (M-FISH) images. The algorithm has been tested on a comprehensive M-FISH database that we established, demonstrating improved performance in classification. When compared with other pixel-wise M-FISH image classifiers such as fuzzy c-means (FCM) clustering algorithms and adaptive fuzzy c-means (AFCM) clustering algorithms that we proposed earlier the current method gave the lowest classification error. In order to evaluate the performance of different SRC for M-FISH imaging analysis, three different sparse representation methods, namely, Homotopy method, Orthogonal Matching Pursuit (OMP), and Least Angle Regression (LARS), were tested and compared. Results from our statistical analysis have shown that Homotopy based method is significantly better than the other two methods. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665392", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1397, "text": "Fluorescence in situ hybridization (FISH) is used to study the organization and the positioning of specific DNA sequences within the cell nucleus. Analyzing the data from FISH images is a tedious process that invokes an element of subjectivity. Automated FISH image analysis offers savings in time as well as gaining the benefit of objective data analysis. While several FISH image analysis software tools have been developed, they often use a threshold-based segmentation algorithm for nucleus segmentation. As fluorescence signal intensities can vary significantly from experiment to experiment, from cell to cell, and within a cell, threshold-based segmentation is inflexible and often insufficient for automatic image analysis, leading to additional manual segmentation and potential subjective bias. To overcome these problems, we developed a graphical software tool called FISH Finder to automatically analyze FISH images that vary significantly. By posing the nucleus segmentation as a classification problem, compound Bayesian classifier is employed so that contextual information is utilized, resulting in reliable classification and boundary extraction. This makes it possible to analyze FISH images efficiently and objectively without adjustment of input parameters. Additionally, FISH Finder was designed to analyze the distances between differentially stained FISH probes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21310746", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1417, "text": "The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining. Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21656271", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1516, "text": "The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20966547", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1513, "text": "The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell.Methods: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion.Results: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20639591", "endSection": "abstract" } ] }, { "body": "How do histone methyltransferases cause histone modification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19571682", "http://www.ncbi.nlm.nih.gov/pubmed/20026581", "http://www.ncbi.nlm.nih.gov/pubmed/17468742", "http://www.ncbi.nlm.nih.gov/pubmed/18058811", "http://www.ncbi.nlm.nih.gov/pubmed/12893173", "http://www.ncbi.nlm.nih.gov/pubmed/17846168", "http://www.ncbi.nlm.nih.gov/pubmed/12154089", "http://www.ncbi.nlm.nih.gov/pubmed/17548343", "http://www.ncbi.nlm.nih.gov/pubmed/17584191", "http://www.ncbi.nlm.nih.gov/pubmed/11316813", "http://www.ncbi.nlm.nih.gov/pubmed/14690609", "http://www.ncbi.nlm.nih.gov/pubmed/22483804", "http://www.ncbi.nlm.nih.gov/pubmed/16581777", "http://www.ncbi.nlm.nih.gov/pubmed/20305384", "http://www.ncbi.nlm.nih.gov/pubmed/23150054", "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "http://www.ncbi.nlm.nih.gov/pubmed/18846226", "http://www.ncbi.nlm.nih.gov/pubmed/22476432", "http://www.ncbi.nlm.nih.gov/pubmed/11850410", "http://www.ncbi.nlm.nih.gov/pubmed/15775980", "http://www.ncbi.nlm.nih.gov/pubmed/16409643", "http://www.ncbi.nlm.nih.gov/pubmed/18231586", "http://www.ncbi.nlm.nih.gov/pubmed/22393255", "http://www.ncbi.nlm.nih.gov/pubmed/18498648", "http://www.ncbi.nlm.nih.gov/pubmed/23195220" ], "ideal_answer": [ "Histone methyltransferases (HMTs) are responsible for the site-specific addition of covalent modifications on the histone tails, which serve as markers for the recruitment of chromatin organization complexes. There are two major types of HMTs: histone-lysine N-Methyltransferases and histone-arginine N-methyltransferases. The former methylate specific lysine (K) residues such as 4, 9, 27, 36, and 79 on histone H3 and residue 20 on histone H4. The latter methylate arginine (R) residues such as 2, 8, 17, and 26 on histone H3 and residue 3 on histone H4. Depending on what residue is modified and the degree of methylation (mono-, di- and tri-methylation), lysine methylation of histones is linked to either transcriptionally active or silent chromatin." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011495", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016570", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008469" ], "type": "summary", "id": "51659356298dcd4e5100005a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23195220", "endSection": "sections.0" }, { "offsetInBeginSection": 512, "offsetInEndSection": 706, "text": "This approach identified Txr1p as a histone methyltransferase in Tetrahymena thermophila and characterized the relationships of the Txr1p and Ezl2p methyltransferases to histone H3 modification.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150054", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "Histone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1-MLL4) whose specific functions are largely unknown. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22483804", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Epigenetic regulation of gene expression by covalent modification of histones is important for germ line cell development. In mammals, histone H3 lysine 9 (H3K9)-specific histone methyltransferases (HMTases), such as G9a, SETDB1, and SUV39H, play critical roles, but the contribution of H3K9-specific HMTases in Drosophila remains to be clarified, especially in male sperm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476432", "endSection": "sections.0" }, { "offsetInBeginSection": 288, "offsetInEndSection": 566, "text": "By analyzing the distribution of histone modifications in nuclei using quantitative fluorescence microscopy, we found that H4K16 acetylation (H4K16ac) is underrepresented and H4K20 monomethylation (H4K20me1) is enriched on hermaphrodite X chromosomes in a DCC-dependent manner. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22393255", "endSection": "sections.0" }, { "offsetInBeginSection": 723, "offsetInEndSection": 888, "text": " Here, we found the epigenetic modification of the BZLF1 promoter in latent Raji cells by histone H3 lysine 27 trimethylation (H3K27me3), H3K9me2/me3, and H4K20me3. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "endSection": "sections.0" }, { "offsetInBeginSection": 144, "offsetInEndSection": 441, "text": "Although DNA methyltransferases have been shown to interact with histone methyltransferases such as EZH2 (which methylates histone H3 on lysine 27) and G9a (which methylates histone H3 on lysine 9), the relationship between DNA methylation and repressive histone marks has not been fully studied. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20305384", "endSection": "sections.0" }, { "offsetInBeginSection": 408, "offsetInEndSection": 685, "text": "Methylation of histone H4 lysine 20 (H4K20me) plays critical roles in diverse cellular processes such as gene expression, cell cycle progression and DNA damage repair, with each of the three degrees of methylation (mono-, di- and tri-methylation) making a unique contribution. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571682", "endSection": "sections.0" }, { "offsetInBeginSection": 339, "offsetInEndSection": 498, "text": "Histone H3-lysine (K) 4, H3-K9 and H3-K27 modifications in all these four genes were examined by chromatin immunoprecipitation (ChIP) assay in HCC cell lines. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584191", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The histone H4 N-terminal tail has long been regarded as a major regulator in chromatin structure and function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17548343", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Gene transcription is critically influenced by chromatin structure and the modification status of histone tails. Methylation of lysine residues in histone tails is dynamically regulated by the opposing activities of histone methyltransferases and histone demethylases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17468742", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The SAS3-dependent NuA3 histone acetyltransferase complex was originally identified on the basis of its ability to acetylate histone H3 in vitro.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16581777", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "SU(VAR)3-9 like histone methyltransferases control heterochromatic domains in eukaryotes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15775980", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Methylation of position-specific lysine residues in histone N termini is a central modification for regulating epigenetic transitions in chromatin. Each methylatable lysine residue can exist in a mono-, di-, or trimethylated state, thereby extending the indexing potential of this particular modification. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14690609", "endSection": "sections.0" }, { "offsetInBeginSection": 126, "offsetInEndSection": 259, "text": "One of these modifications, histone lysine methylation, has been shown to be highly stable and to represent an epigenetic alteration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12893173", "endSection": "sections.0" }, { "offsetInBeginSection": 282, "offsetInEndSection": 540, "text": "Primarily because of the recent discovery of the SET domain-depending H3-specific histone methyltransferases SUV39H1 and Suv39h1, which selectively methylate lysine 9 of the H3 N terminus, this posttranslational modification has regained scientific interest.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12154089", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850410", "endSection": "title" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1168, "text": "Our results suggest that the methylation of histone tails can have distinct effects on transcription, depending on its chromosomal location, the combination of posttranslational modifications, and the enzyme (or protein complex) involved in the particular modification.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850410", "endSection": "sections.0" }, { "offsetInBeginSection": 164, "offsetInEndSection": 363, "text": "Among the different groups of enzymes known to catalyze the covalent modification, the most recent additions are the histone methyltransferases (HMTases), whose functions are now being characterized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11316813", "endSection": "sections.0" } ] }, { "body": "Is there an increased risk for cancer in Dyskeratosis Congenita?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19327580", "http://www.ncbi.nlm.nih.gov/pubmed/20925138", "http://www.ncbi.nlm.nih.gov/pubmed/18054794", "http://www.ncbi.nlm.nih.gov/pubmed/20507306", "http://www.ncbi.nlm.nih.gov/pubmed/23352883", "http://www.ncbi.nlm.nih.gov/pubmed/22362038", "http://www.ncbi.nlm.nih.gov/pubmed/20301779", "http://www.ncbi.nlm.nih.gov/pubmed/18938267", "http://www.ncbi.nlm.nih.gov/pubmed/17825470", "http://www.ncbi.nlm.nih.gov/pubmed/22058220", "http://www.ncbi.nlm.nih.gov/pubmed/22932338", "http://www.ncbi.nlm.nih.gov/pubmed/24034063", "http://www.ncbi.nlm.nih.gov/pubmed/23541441", "http://www.ncbi.nlm.nih.gov/pubmed/19558498", "http://www.ncbi.nlm.nih.gov/pubmed/23619122" ], "ideal_answer": [ "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis ", "Yes. Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer. Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST)", "People with Dyskeratosis Congenita are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.disease-ontology.org/api/metadata/DOID:2729", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369" ], "type": "yesno", "id": "54ede5df94afd61504000007", "snippets": [ { "offsetInBeginSection": 288, "offsetInEndSection": 544, "text": "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19327580", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 790, "text": "Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23352883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS). Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507306", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1026, "text": "Patients with FA had earlier onset of cancers, need for stem cell transplant, and death; followed by DC; DBA and SDS were mildest. While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507306", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1232, "text": "The findings demonstrate that both FA and DC are major cancer susceptibility syndromes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507306", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 544, "text": "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23619122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Dyskeratosis congenita (DC) is characterized by the clinical triad of reticular skin pigmentation, oral leukoplakia, and nail dystrophy associated with bone marrow failure (BMF) and an high risk to develop cancer and pulmonary complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24034063", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 718, "text": "CONCLUSION: Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22932338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20925138", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 212, "text": "Dyskeratosis Congenita (DC) also known as Zinsser-Engman-Cole syndrome is a rare multi-system bone marrow failure syndrome characterised by mucocutaneous abnormalities and an increased predisposition to cancer\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18054794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17825470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22932338", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 243, "text": "Epidermal atrophy, hair growth defects, bone marrow failure and increased risk of cancer are also common in DC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19558498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Telomere dysfunction and tumor suppression responses in dyskeratosis congenita: balancing cancer and tissue renewal impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23541441", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23619122", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 682, "text": "Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22932338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17825470", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1026, "text": "While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507306", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1341, "text": "As in Fanconi anemia and dyskeratosis congenita, DBA is both an inherited bone marrow failure syndrome and a cancer predisposition syndrome; cancer risks appear lower in DBA than in Fanconi anemia or dyskeratosis congenita", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362038", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 417, "text": "Severe pancytopenia frequently causes early mortality of DC patients, who have an increased risk of developing oropharyngeal squamous cell carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18938267", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 1048, "text": "Here different aspects of telomere biology, concerning adult stem cells senescence, tumor suppression and cancer are considered in the context of DC, resulting in two translational models: late onset of DC symptoms in telomere-related mutations carriers is a potential indicator of increased cancer risk and differences in tumor suppression capacities among the genetic subgroups are (at least partial) causes of different clinical manifestations of the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23541441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20925138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Dyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058220", "endSection": "abstract" } ] }, { "body": "Does MicroRNA-21 (miR-21) contribute to cardiovascular disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19043405", "http://www.ncbi.nlm.nih.gov/pubmed/22960625", "http://www.ncbi.nlm.nih.gov/pubmed/20649511", "http://www.ncbi.nlm.nih.gov/pubmed/20980922", "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "http://www.ncbi.nlm.nih.gov/pubmed/19336275", "http://www.ncbi.nlm.nih.gov/pubmed/20219857", "http://www.ncbi.nlm.nih.gov/pubmed/20959496", "http://www.ncbi.nlm.nih.gov/pubmed/20015039", "http://www.ncbi.nlm.nih.gov/pubmed/23691029", "http://www.ncbi.nlm.nih.gov/pubmed/21712654", "http://www.ncbi.nlm.nih.gov/pubmed/22859901", "http://www.ncbi.nlm.nih.gov/pubmed/19706597", "http://www.ncbi.nlm.nih.gov/pubmed/22882958", "http://www.ncbi.nlm.nih.gov/pubmed/21464712" ], "ideal_answer": [ "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.disease-ontology.org/api/metadata/DOID:1287" ], "type": "yesno", "id": "54f4703764850a5854000008", "snippets": [ { "offsetInBeginSection": 1167, "offsetInEndSection": 1329, "text": "The synergistic effect of miR-21 and miR-1 were functionally validated for their significant influences on myocardial apoptosis, cardiac hypertrophy and fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23691029", "endSection": "abstract" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1682, "text": "Taken together, we found a novel reciprocal loop between miR-21 and TGF\u03b2RIII in cardiac fibrosis caused by myocardial infarction in mice, and targeting this pathway could be a new strategy for the prevention and treatment of myocardial remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960625", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 316, "text": "It is still controversial whether microRNA-21 (miR-21) participates in the process of cardiac fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960625", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 288, "text": "In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22882958", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1135, "text": "The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22882958", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1751, "text": "Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22882958", "endSection": "abstract" }, { "offsetInBeginSection": 1736, "offsetInEndSection": 1914, "text": "Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859901", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1309, "text": "In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type \u2160, type \u2162 and PCNA positive cells all significantly decreased compared with the Ad-GFP group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859901", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 825, "text": "While miR-21, -133, -150, -195, and -214 regulate cardiomyocyte hypertrophy, miR-1/-133 and miR-208 have been elucidated to influence myocardial contractile function. In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis. Myocardial fibrosis can be regulated by the miR-29 family and miR-21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The small regulatory RNA microRNA-21 (miR-21) plays a crucial role in a plethora of biological functions and diseases including development, cancer, cardiovascular diseases and inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21712654", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 907, "text": "During recent years, additional roles of miR-21 in cardiovascular and pulmonary diseases, including cardiac and pulmonary fibrosis as well as myocardial infarction have been described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21712654", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 758, "text": "On the other hand, miR-21, miR-199a, miR-210, and miR-494 have been proven critical for the myocytes' adaptation and survival during hypoxia/ischemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21464712", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 858, "text": "Studies have shown that several miRs, including miR-1, miR-133, miR-21, miR-126, miR-320, miR-92a, and miR-199a, are regulated after preconditioning and play an active role in protecting the heart against ischemia/reperfusion injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20980922", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1053, "text": "Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20959496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 672, "text": "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 993, "text": "miR-21 might be a novel therapeutic target in cardiovascular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1103, "text": "This review article summarizes the research progress regarding the roles of miR-21 in cardiovascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 1173, "text": "Remarkably, miR-21 was one of most upregulated miRNAs in hearts after IP. In vivo, IP-mediated cardiac protection against ischaemia/reperfusion injury was inhibited by knockdown of cardiac miR-21. In cultured cardiac myocytes, we identified that miR-21 also had a protective effect on hypoxia/reoxygenation-induced cell apoptosis that was associated with its target gene, programmed cell death 4. The protective effect of miR-21 on cardiac cell apoptosis was further confirmed in rat hearts after ischaemia/reperfusion injury in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219857", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 747, "text": "Lately, some highlight articles revealed that the altered expression of miRNAs such as miR-1, miR-133, miR-21, miR-208 etc in hearts also contributed to cardiovascular diseases, such as heart ischemia, cardiac hypertrophy, and arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20015039", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 1537, "text": "Remarkably, miR-21 expression was significantly down-regulated in infarcted areas, but was up-regulated in border areas. The down-regulation of miR-21 in the infarcted areas was inhibited by ischemic preconditioning, a known cardiac protective method. Overexpression of miR-21 via adenovirus expressing miR-21 (Ad-miR-21) decreased myocardial infarct size by 29% at 24 h and decreased the dimension of left ventricles at 2 weeks after AMI. Using both gain-of-function and loss-of-function approaches in cultured cardiac myocytes, we identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that was associated with its target gene programmed cell death 4 and activator protein 1 pathway. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by decreased cell apoptosis in the border and infarcted areas of the infarcted rat hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19706597", "endSection": "abstract" }, { "offsetInBeginSection": 1439, "offsetInEndSection": 1792, "text": "The results suggest that miR-21 is sensitive to H(2)O(2) stimulation. miR-21 participates in H(2)O(2)-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043405", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22882958", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859901", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336275", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043405", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 992, "text": "miR-21 might be a novel therapeutic target in cardiovascular diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "MicroRNA-21 as therapeutic target in cancer and cardiovascular disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20649511", "endSection": "title" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1273, "text": "These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043405", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1451, "text": "Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043405", "endSection": "abstract" } ] }, { "body": "What is the enzymatic activity of the breast cancer associated gene BRCA1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20681793", "http://www.ncbi.nlm.nih.gov/pubmed/24278741", "http://www.ncbi.nlm.nih.gov/pubmed/15254397", "http://www.ncbi.nlm.nih.gov/pubmed/16479151", "http://www.ncbi.nlm.nih.gov/pubmed/16710298", "http://www.ncbi.nlm.nih.gov/pubmed/17420471", "http://www.ncbi.nlm.nih.gov/pubmed/22034435", "http://www.ncbi.nlm.nih.gov/pubmed/19088202" ], "ideal_answer": [ "E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain.BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways.", "Discovering the precise function of the breast and ovarian specific tumor suppressor, BRCA1, has proven to be quite complicated. The protein encoded by BRCA1 interacts in vivo with the related BARD1 protein to form a heterodimeric complex that acts as a ubiquitin E3 ligase. E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain." ], "exact_answer": [ "E3 ubiquitin ligase activity" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070531", "http://www.uniprot.org/uniprot/BRCA1_GORGO" ], "type": "factoid", "id": "552421082c8b63434a000005", "snippets": [ { "offsetInBeginSection": 347, "offsetInEndSection": 478, "text": "E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20681793", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 852, "text": "BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24278741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "E3 ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19088202", "endSection": "title" }, { "offsetInBeginSection": 291, "offsetInEndSection": 609, "text": "The protein encoded by BRCA1 interacts in vivo with the related BARD1 protein to form a heterodimeric complex that acts as a ubiquitin E3 ligase. Because the enzymatic activity of the BRCA1/BARD1 heterodimer is conserved over a broad phylogenetic range, it is thought to be critical for the central functions of BRCA1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19088202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "A mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17420471", "endSection": "title" }, { "offsetInBeginSection": 508, "offsetInEndSection": 772, "text": "In this study, we identified an ubiquitin-dependent mechanism by which BRCA1 inhibits transcription. BRCA1 ubiquitinates the transcriptional preinitiation complex, preventing stable association of TFIIE and TFIIH, and thus blocks the initiation of mRNA synthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17420471", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 937, "text": "In the structure the arrangement of the Ring-domains is similar to another H2A E3 ligase, the BRCA1/BARD1 complex, but complex formation depends on an N-terminal arm of Ring1b that embraces the Bmi1 Ring-domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16710298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "Discovering the precise function of the breast and ovarian specific tumor suppressor, BRCA1, has proven to be quite complicated. It has been determined that BRCA1, together with BARD1, comprise an E3 ubiquitin ligase. Since it is now known that BRCA1 is an enzyme, the challenge for BRCA1 research is to learn how this enzymatic activity functions in normal breast and ovarian cells in order to suppress cancerous transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16479151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "The BRCA1 tumor suppressor gene is expressed in all mammalian cells. Within these cells, the BRCA1 protein product interacts with several seemingly distinct nuclear complexes. Proteins within these complexes are potential targets for the E3-ubiquitin ligase activity associated with BRCA1:BARD1 complexes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15254397", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 765, "text": "During both DNA replication and DNA repair, BRCA1 appears to serve both adaptor and enzymatic functions. Roles include transient physical recruitment of NBS1, gammaH2AX, FANCD2 and other proteins in specific repair associated complexes, and enzymatic activity as an E3-ubiquitin ligase against a subset of these proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15254397", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 245, "text": "The BRCA1 protein displays E3 ubiquitin ligase activity, and this enzymatic function is thought to be required for tumor suppression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22034435", "endSection": "abstract" } ] }, { "body": "List markers for autophagy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22807527", "http://www.ncbi.nlm.nih.gov/pubmed/23940944", "http://www.ncbi.nlm.nih.gov/pubmed/23737395", "http://www.ncbi.nlm.nih.gov/pubmed/23626658", "http://www.ncbi.nlm.nih.gov/pubmed/24141623", "http://www.ncbi.nlm.nih.gov/pubmed/24126619", "http://www.ncbi.nlm.nih.gov/pubmed/23193914", "http://www.ncbi.nlm.nih.gov/pubmed/24255881", "http://www.ncbi.nlm.nih.gov/pubmed/24291536", "http://www.ncbi.nlm.nih.gov/pubmed/23437259", "http://www.ncbi.nlm.nih.gov/pubmed/23608825", "http://www.ncbi.nlm.nih.gov/pubmed/24231340", "http://www.ncbi.nlm.nih.gov/pubmed/23727153", "http://www.ncbi.nlm.nih.gov/pubmed/23182945", "http://www.ncbi.nlm.nih.gov/pubmed/23598404", "http://www.ncbi.nlm.nih.gov/pubmed/23117929", "http://www.ncbi.nlm.nih.gov/pubmed/22652752", "http://www.ncbi.nlm.nih.gov/pubmed/23822101" ], "ideal_answer": [ "Expression of LC3-II and BECN1 as well as SQSTM1 are used as markers of autophagy activity." ], "exact_answer": [ [ "LC3-II", "microtubule-associated protein 1 light chain 3" ], [ "BECN1", "beclin 1" ], [ "SQSTM1", "p62", "Sequestosome 1" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000943", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343" ], "type": "list", "id": "5505b9ff8e1671127b000001", "snippets": [ { "offsetInBeginSection": 536, "offsetInEndSection": 580, "text": ". Light chain 3/Atg8 as an autophagy marker ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291536", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1235, "text": "increased conversion of microtubule-associated protein, 1A/1B-light chain 3, from its cytosolic form (LC3B-I) to its lipidated form (LC3B-II), increased Beclin-1 levels, and increased acridine orange staining as determined by flow cytometry analysis, providing further evidence of \u03b3-tocotrienol-induced autophagy in these mammary cancer cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231340", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1070, "text": "Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3 (LC3)-II protein expression as a marker for autophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255881", "endSection": "abstract" }, { "offsetInBeginSection": 1821, "offsetInEndSection": 1844, "text": "autophagy marker LC3-II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255881", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 41, "text": "autophagy marker LC3B ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141623", "endSection": "title" }, { "offsetInBeginSection": 498, "offsetInEndSection": 522, "text": "the autophagy marker LC3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24126619", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 562, "text": "autophagy marker molecules, p62 and LC3-II ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940944", "endSection": "abstract" }, { "offsetInBeginSection": 1635, "offsetInEndSection": 1742, "text": " LC3-I into LC3-II and has been confirmed in multiple mammalian cell lines with multiple autophagy markers ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23822101", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 685, "text": " light chain 3 (LC3), which is an autophagy marker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23737395", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 904, "text": "LC3 (tfLC3) autophagy marker", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23727153", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 684, "text": "the autophagy marker LC3,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23608825", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 731, "text": "autophagy marker beclin 1 and microtubule-associated protein light chain 3 (LC3) were analyzed in control, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23626658", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 925, "text": " LC3-II levels (an autophagy marker);", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23598404", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 918, "text": "autophagy marker, microtubule-associated protein light chain3 (LC3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23437259", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1257, "text": "the autophagy marker LC3B-II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193914", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 480, "text": "utophagy marker protein microtubule-associated protein 1 light chain 3 (LC3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182945", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 594, "text": "autophagy marker LC3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23117929", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 320, "text": "We used the expression of LC3-II and BECN1 as well as SQSTM1 as markers of autophagy activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22652752", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1102, "text": "autophagy marker LC3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22807527", "endSection": "abstract" } ] }, { "body": "Are there any statistical methods for normalizing and identifying differential regions in histone modification ChIP-seq data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22870189" ], "ideal_answer": [ "Yes. ChIPnorm is a two-stage statistical method to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016570", "http://www.biosemantics.org/jochem#4278518" ], "type": "yesno", "id": "56b29bf545561f0573000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "title" }, { "offsetInBeginSection": 444, "offsetInEndSection": 1264, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 879, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 664, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 789, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 663, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 789, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 664, "text": "This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 664, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" } ] }, { "body": "Is CD84 genetically associated with arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21094032", "http://www.ncbi.nlm.nih.gov/pubmed/21255096", "http://www.ncbi.nlm.nih.gov/pubmed/23555300" ], "ideal_answer": [ "Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations. Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with Rheumatoid Arthritis disease activity." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001168", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.disease-ontology.org/api/metadata/DOID:7148" ], "type": "yesno", "id": "52ef7170c8da898910000012", "snippets": [ { "offsetInBeginSection": 901, "offsetInEndSection": 1241, "text": "The SNP is predicted to disrupt transcription factor binding site motifs in the 3' UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1 \u00d7 10(-11) in 228 non-RA patients and P = 0.004 in 132 RA patients)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555300", "endSection": "abstract" }, { "offsetInBeginSection": 1748, "offsetInEndSection": 1944, "text": "Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555300", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 352, "text": " Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21094032", "endSection": "abstract" } ] }, { "body": "What is the function of Neu5Gc (N-Glycolylneuraminic acid)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25003133", "http://www.ncbi.nlm.nih.gov/pubmed/25124893", "http://www.ncbi.nlm.nih.gov/pubmed/18669916", "http://www.ncbi.nlm.nih.gov/pubmed/23945141", "http://www.ncbi.nlm.nih.gov/pubmed/23520510", "http://www.ncbi.nlm.nih.gov/pubmed/11786991" ], "ideal_answer": [ "N-glycolylneuraminic acid (Neu5Gc) is an immunogenic sugar of dietary origin that metabolically incorporates into diverse native glycoconjugates in humans. Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. N-Glycolylneuraminic acid (Neu5Gc) can be incorporated in human cells and can trigger immune response, a response that is diverse and polyclonal. As dietary Neu5Gc is primarily found in red meat and milk products, it is suggested that this ongoing antigen-antibody reaction may generate chronic inflammation, possibly contributing to the high frequency of diet-related carcinomas and other diseases in humans." ], "exact_answer": [ "Neu5Gc is an immune message to self" ], "concepts": [ "http://www.biosemantics.org/jochem#4256873", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019158" ], "type": "factoid", "id": "5719f5b27de986d80d00000c", "snippets": [ { "offsetInBeginSection": 77, "offsetInEndSection": 250, "text": "Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25124893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "N-glycolylneuraminic acid (Neu5Gc) is an immunogenic sugar of dietary origin that metabolically incorporates into diverse native glycoconjugates in humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23520510", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 195, "text": "N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid synthesized by animals, but not by humans or birds. However, it can be incorporated in human cells and can trigger immune response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Human heterophile antibodies that agglutinate animal erythrocytes are known to detect the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18669916", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 416, "text": " the human anti-Neu5Gc antibody response is diverse and polyclonal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18669916", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1677, "text": "As dietary Neu5Gc is primarily found in red meat and milk products, we suggest that this ongoing antigen-antibody reaction may generate chronic inflammation, possibly contributing to the high frequency of diet-related carcinomas and other diseases in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18669916", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1247, "text": "These data suggest that anti-Neu5Gc Abs represent a barrier for long-term acceptance of porcine xenografts. Because anti-Neu5Gc Abs can promote chronic inflammation, the long-term safety of living and acellular pig tissue implants in recipients warrants further evaluation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945141", "endSection": "abstract" } ] }, { "body": "Are there any specific antidotes for rivaroxaban?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12871541", "http://www.ncbi.nlm.nih.gov/pubmed/23117666", "http://www.ncbi.nlm.nih.gov/pubmed/23312927", "http://www.ncbi.nlm.nih.gov/pubmed/19351313", "http://www.ncbi.nlm.nih.gov/pubmed/23821689", "http://www.ncbi.nlm.nih.gov/pubmed/24170233", "http://www.ncbi.nlm.nih.gov/pubmed/24103671", "http://www.ncbi.nlm.nih.gov/pubmed/23810130", "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "http://www.ncbi.nlm.nih.gov/pubmed/20858186", "http://www.ncbi.nlm.nih.gov/pubmed/23628464", "http://www.ncbi.nlm.nih.gov/pubmed/23953907", "http://www.ncbi.nlm.nih.gov/pubmed/23866358", "http://www.ncbi.nlm.nih.gov/pubmed/23460104", "http://www.ncbi.nlm.nih.gov/pubmed/23657589", "http://www.ncbi.nlm.nih.gov/pubmed/22353706", "http://www.ncbi.nlm.nih.gov/pubmed/23790307", "http://www.ncbi.nlm.nih.gov/pubmed/23634925", "http://www.ncbi.nlm.nih.gov/pubmed/22308807" ], "ideal_answer": [ "Currently, there is no specific antidote for rivaroxaban" ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000931", "http://www.biosemantics.org/jochem#4243836" ], "type": "yesno", "id": "532f08b8d6d3ac6a34000029", "snippets": [ { "offsetInBeginSection": 172, "offsetInEndSection": 490, "text": "Novel oral anticoagulants (NOACs)--apixaban, dabigatran, and rivaroxaban--have a significantly smaller risk of intracerebral hemorrhage (ICH). However, two facts make this situation complicated: First, the risk of hematoma expansion is unknown for NOACs. Second, there is no specific antidote for neither of the NOACs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24103671", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 414, "text": "he new oral anticoagulants dabigatran etexilate (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many physicians are wary of these drugs, since there is limited evidence on how to manage bleeding in patients taking them, and since no specific antidote is known to reverse their anticoagulant effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821689", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 592, "text": "Given the absence of a specific antidote, the action to be taken in these situations must be defined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810130", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1176, "text": "The fact that there is no specific antidote to reverse the anticoagulant action of the new anticoagulants can impair management of hemorrhagic complications; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23790307", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 537, "text": "Like any new therapy, the potential benefits must be weighed against the potential challenges and one of the most concerning aspects of the new target-specific oral anticoagulants is the lack of a proven method to reverse their effect. Unlike the vitamin K antagonist, i.e. warfarin, there is no specific antidote for these medications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23657589", "endSection": "abstract" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1598, "text": "Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460104", "endSection": "abstract" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1741, "text": "NOA also have other unresolved problems: drug interactions are still possible, specific coagulation test to assess them must be developed, and no specific antidote is currently available in case of hemorrhagic complication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312927", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1333, "text": "But they have disadvantages also, they depend on renal clearance, they can interact with other medicaments and they lack a specific antidote. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23117666", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 957, "text": "While these trial data are extremely encouraging, several practical issues (e.g., lack of specific antidote, safety of long-term treatment or cost-effectiveness in \"real-life\" clinical practice) still need to be elucidated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22353706", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 661, "text": "In case of massive bleeding, management is unclear and none of these newer agents has a specific antidote that completely reverses its anticoagulant effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22308807", "endSection": "abstract" }, { "offsetInBeginSection": 1935, "offsetInEndSection": 2044, "text": "The short half-life of these new agents compensates for the lack of any specific antidote in many instances. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 750, "text": "Currently, none of these new agents has a specific antidote, and little advise can be given on how to manage a major bleeding event.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20858186", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 865, "text": "Rivaroxaban, which inhibits activated factor X (Xa), is currently in clinical trials and is the most advanced factor Xa inhibitor. The drug offers once-daily oral dosing, with no need for injections, dose titration, or frequent blood tests to monitor the international normalised ratio. It has a rapid onset of action and, although there is no specific antidote, it has a short plasma elimination half-life (about 5-9 hours). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19351313", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 731, "text": "Increased use of dabigatran, rivaroxaban, and apixaban as oral anticoagulants for the treatment of atrial fibrillation and acute deep venous thrombosis has increased despite the lack of known antidotes to these medications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23634925", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 812, "text": "There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628464", "endSection": "abstract" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1570, "text": "Further concerns about the use of NOAC in the elderly are the high prevalence of renal insufficiency in AF patients >75 years of age, the largely unknown risk of drug-drug and drug-food interactions, the lack of easily available laboratory monitoring tests of anticoagulant activity and the lack of an antidote.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170233", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 576, "text": "Specific antidotes for the reversal of the anticoagulant effect of these drugs, such as monoclonal antibodies against the direct thrombin inhibitor dabigatran or recombinant Xa-analog in the case of factor Xa inhibitors, are still being investigated in early clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23953907", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1596, "text": "In early 2013 there is no antidote for dabigatran, rivaroxaban or apixaban, nor any specific treatment with proven efficacy for severe bleeding linked to these drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23866358", "endSection": "abstract" } ] }, { "body": "Which metabolite activates AtxA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "http://www.ncbi.nlm.nih.gov/pubmed/15149039", "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "http://www.ncbi.nlm.nih.gov/pubmed/17302798" ], "ideal_answer": [ "Upon infection of a mammalian host, Bacillus anthracis responds to host cues, and particularly to elevated temperature (37\u00b0C) and bicarbonate/CO2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer. Cultures grown with elevated CO(2) /bicarbonate exhibited increased AtxA dimer/monomer ratios and increased AtxA activity, relative to cultures grown without added CO(2) /bicarbonate, suggesting that this host-associated signal enhances AtxA function by shifting the dimer/monomer equilibrium towards the dimeric state. CO2-enhanced toxin gene transcription is not observed in atx4-null mutants. Overall data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.", "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2. However, the steady-state level of atxA mRNA in cells grown in elevated CO2/bicarbonate at 37 degrees C is five- to sixfold higher than that observed in cells grown in the same conditions at 28 degrees C. A corresponding difference in AtxA protein was also seen at the different growth temperatures. All mutants multimerized, but one mutation, C402S, prevented cross-linking." ], "exact_answer": [ "CO2", "bicarbonate" ], "concepts": [ "http://www.uniprot.org/uniprot/ATXA_BACAN" ], "type": "factoid", "id": "5710a592cf1c32585100002a", "snippets": [ { "offsetInBeginSection": 217, "offsetInEndSection": 471, "text": "Here we report that bioinformatic analyses suggested the presence in AtxA of two PTS (phosphenolpyruvate : sugar phosphotransferase system) regulation domains (PRD) generally regulated by phosphorylation/dephosphorylation at conserved histidine residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302798", "endSection": "abstract" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1342, "text": "Our results link virulence factor production in B. anthracis to carbohydrate metabolism and, for the first time, provide a mechanistic explanation for AtxA transcriptional activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302798", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 286, "text": "Upon infection of a mammalian host, Bacillus anthracis responds to host cues, and particularly to elevated temperature (37\u00b0C) and bicarbonate/CO2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 330, "text": "The 475 amino acid sequence of AtxA reveals DNA binding motifs and regions similar to proteins associated with the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "endSection": "abstract" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1577, "text": "cultures grown with elevated CO(2) /bicarbonate exhibited increased AtxA dimer/monomer ratios and increased AtxA activity, relative to cultures grown without added CO(2) /bicarbonate, suggesting that this host-associated signal enhances AtxA function by shifting the dimer/monomer equilibrium towards the dimeric state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Transcription of the major Bacillus anthracis virulence genes is triggered by CO2, a signal mimicking the host environment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15149039", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 941, "text": "Furthermore, in vitro in presence of CO2 and in vivo, AtxA is part of the sap and eag regulatory network. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15149039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Regulation of anthrax toxin activator gene (atxA) expression in Bacillus anthracis: temperature, not CO2/bicarbonate, affects AtxA synthesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "endSection": "title" }, { "offsetInBeginSection": 165, "offsetInEndSection": 332, "text": " In atxA+ strains, expression of the toxin genes (pag, lef, and cya) is enhanced by two physiologically significant signals: elevated CO2/bicarbonate and temperature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1130, "text": "Our data indicate that atxA expression is not influenced by CO2/bicarbonate levels. However, the steady-state level of atxA mRNA in cells grown in elevated CO2/bicarbonate at 37 degrees C is five- to sixfold higher than that observed in cells grown in the same conditions at 28 degrees C. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 418, "text": "CO2-enhanced toxin gene transcription is not observed in atx4-null mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 837, "text": "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1293, "text": "Transposon-insertion libraries were screened for mutants expressing CO2-enhanced atxA-dependent beta-galactosidase activity. DNA sequence analysis of transposon insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed 10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which did not map to the toxin genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1648, "text": "data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "abstract" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1703, "text": "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The anthrax toxin activator gene atxA is associated with CO2-enhanced non-toxin gene expression in Bacillus anthracis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2 through an AtxA-dependent mechanism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "title" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1581, "text": "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2 through an AtxA-dependent mechanism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 271, "text": "Expression of the toxin genes by B. anthracis is enhanced during growth under elevated levels of CO2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 407, "text": "This CO2 effect is observed only in the presence of another pXO1 gene, atxA, which encodes a transactivator of anthrax toxin synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 532, "text": "Here we show that transcription of atxA does not appear to differ in cells grown in 5% CO2 compared with cells grown in air.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1756, "text": "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate. Deletion analysis of the upstream region of the cap promoter revealed that activation by both atxA and acpA required a DNA segment of 70 bp extending upstream of the P1 site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1581, "text": "We identified two major apparent transcriptional start sites, designated P1 and P2, located at positions 731 bp and 625 bp, respectively, upstream of the translation-initiation codon of capB. Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1581, "text": "Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Regulation of anthrax toxin activator gene (atxA) expression in Bacillus anthracis: temperature, not CO2/bicarbonate, affects AtxA synthesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The anthrax toxin activator gene atxA is associated with CO2-enhanced non-toxin gene expression in Bacillus anthracis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "title" } ] }, { "body": "What is the function of 6SRNA in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/58611", "http://www.ncbi.nlm.nih.gov/pubmed/17332013", "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "http://www.ncbi.nlm.nih.gov/pubmed/23667906", "http://www.ncbi.nlm.nih.gov/pubmed/22214309", "http://www.ncbi.nlm.nih.gov/pubmed/2579060" ], "ideal_answer": [ "6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase. Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. The carboxy terminus containing the Arg-Gly-Gly (RGG) repeat domains in these proteins are necessary for cis-repression of transcription activation and HAT activity by the N-terminal glutamine-rich domain.", "Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. 6S RNA-deficient cells are at a disadvantage for survival in stationary phase, a time when 6S RNA regulates transcription. 6S RNA regulation of both sigma(70) and sigma(S) activities contributes to increased cell persistence during nutrient deprivation. 6S RNA acts as a template for the transcription of defined RNA molecules in the absence of DNA. 6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase.", "6S RNA function enhances long-term cell survival. " ], "type": "summary", "id": "57169662cb4ef8864c000008", "snippets": [ { "offsetInBeginSection": 464, "offsetInEndSection": 643, "text": "Qbeta replicase lacking subunit alpha (R-alpha) is capable of replicating templates other than (+) strand, such as (--), \"6S\" RNA, poly(C) etc., in the absence of the host factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/58611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Escherichia coli 6S RNA gene is part of a dual-function transcription unit.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2579060", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 697, "text": "The DNA sequence results confirm the accuracy of the previously established RNA sequence and, with genomic hybridization data, reveal that there is only one copy of the 6S DNA in the chromosome. Consistent with its relaxed mode of expression, the promoter region of the 6S RNA gene was found to lack the hypothetical GC-rich discriminator domain common to other stable RNA genes under stringent control. The sequence results also revealed the occurrence of a 540-base-pair open reading frame immediately downstream from the 6S RNA coding region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2579060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "6S RNA function enhances long-term cell survival.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "endSection": "title" }, { "offsetInBeginSection": 143, "offsetInEndSection": 265, "text": "6S RNA-deficient cells are at a disadvantage for survival in stationary phase, a time when 6S RNA regulates transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 685, "text": "6S RNA inhibition of sigma(70)-dependent transcription was not ubiquitous, in spite of the fact that the vast majority of sigma(70)-RNA polymerase is bound by 6S RNA during stationary phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 856, "text": "The sigma(70)-dependent promoters inhibited by 6S RNA contain an extended -10 promoter element, suggesting that this feature may define a class of 6S RNA-regulated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 980, "text": " a secondary effect of 6S RNA in the activation of sigma(S)-dependent transcription at several promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1128, "text": "6S RNA regulation of both sigma(70) and sigma(S) activities contributes to increased cell persistence during nutrient deprivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17332013", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 702, "text": "Preferred binding of 6S RNA to Esigma(70) was confirmed, however weaker binding to Esigma(38) was also observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17332013", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1355, "text": "Moreover, we show for the first time that 6S RNA acts as a template for the transcription of defined RNA molecules in the absence of DNA. In conclusion, this study reveals new aspects of 6S RNA function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17332013", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 501, "text": "6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22214309", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 746, "text": "The release reaction depends on a characteristic property of 6S RNAs, namely to act as template for the de novo synthesis of small RNAs, termed pRNAs.Here, we used limited hydrolysis with structure-specific RNases and in-line probing of isolated 6S RNA and 6SRNA \u223c pRNA complexes to investigate the molecular details leading to the release reaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23667906", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 748, "text": "The release reaction depends on a characteristic property of 6S RNAs, namely to act as template for the de novo synthesis of small RNAs, termed pRNAs.Here, we used limited hydrolysis with structure-specific RNases and in-line probing of isolated 6S RNA and 6SRNA \u223c pRNA complexes to investigate the molecular details leading to the release reaction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23667906", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 748, "text": "The release reaction depends on a characteristic property of 6S RNAs, namely to act as template for the de novo synthesis of small RNAs, termed pRNAs.Here, we used limited hydrolysis with structure-specific RNases and in-line probing of isolated 6S RNA and 6SRNA \u223c pRNA complexes to investigate the molecular details leading to the release reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23667906", "endSection": "abstract" } ] }, { "body": "Is cytisine superior to nicotine replacement therapy for smoking cessation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22513936", "http://www.ncbi.nlm.nih.gov/pubmed/21154363", "http://www.ncbi.nlm.nih.gov/pubmed/17130378", "http://www.ncbi.nlm.nih.gov/pubmed/22104038", "http://www.ncbi.nlm.nih.gov/pubmed/25517706", "http://www.ncbi.nlm.nih.gov/pubmed/23404838", "http://www.ncbi.nlm.nih.gov/pubmed/23834141", "http://www.ncbi.nlm.nih.gov/pubmed/24574554", "http://www.ncbi.nlm.nih.gov/pubmed/21328282", "http://www.ncbi.nlm.nih.gov/pubmed/18076335", "http://www.ncbi.nlm.nih.gov/pubmed/17825502", "http://www.ncbi.nlm.nih.gov/pubmed/21385905", "http://www.ncbi.nlm.nih.gov/pubmed/18646137", "http://www.ncbi.nlm.nih.gov/pubmed/20040957", "http://www.ncbi.nlm.nih.gov/pubmed/24831822", "http://www.ncbi.nlm.nih.gov/pubmed/17220536", "http://www.ncbi.nlm.nih.gov/pubmed/17253581", "http://www.ncbi.nlm.nih.gov/pubmed/23978314", "http://www.ncbi.nlm.nih.gov/pubmed/23728690" ], "ideal_answer": [ "Yes, one clinical trial that directly compared smoking cessation rates with cytisine versus nicotine replacement therapy reported that cytisine was superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4273701", "http://www.biosemantics.org/jochem#4251343" ], "type": "yesno", "id": "54d77f0e3706e8952800001b", "snippets": [ { "offsetInBeginSection": 1245, "offsetInEndSection": 1541, "text": "The effectiveness of cytisine for continuous abstinence was superior to that of nicotine-replacement therapy at 1 week, 2 months, and 6 months. In a prespecified subgroup analysis of the primary outcome, cytisine was superior to nicotine-replacement therapy among women and noninferior among men.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25517706", "endSection": "abstract" }, { "offsetInBeginSection": 1833, "offsetInEndSection": 2068, "text": "CONCLUSIONS: When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25517706", "endSection": "abstract" } ] }, { "body": "Which amino acid residue appears mutated in most of the cases reported with cadasil syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24086431", "http://www.ncbi.nlm.nih.gov/pubmed/22623959", "http://www.ncbi.nlm.nih.gov/pubmed/23587639", "http://www.ncbi.nlm.nih.gov/pubmed/21772710", "http://www.ncbi.nlm.nih.gov/pubmed/21038489", "http://www.ncbi.nlm.nih.gov/pubmed/11706120", "http://www.ncbi.nlm.nih.gov/pubmed/18710532", "http://www.ncbi.nlm.nih.gov/pubmed/19006080", "http://www.ncbi.nlm.nih.gov/pubmed/16717210", "http://www.ncbi.nlm.nih.gov/pubmed/17726918", "http://www.ncbi.nlm.nih.gov/pubmed/23799017", "http://www.ncbi.nlm.nih.gov/pubmed/22367627", "http://www.ncbi.nlm.nih.gov/pubmed/20224942", "http://www.ncbi.nlm.nih.gov/pubmed/15304596", "http://www.ncbi.nlm.nih.gov/pubmed/22082899", "http://www.ncbi.nlm.nih.gov/pubmed/23597439", "http://www.ncbi.nlm.nih.gov/pubmed/21616505", "http://www.ncbi.nlm.nih.gov/pubmed/19043263", "http://www.ncbi.nlm.nih.gov/pubmed/18313300" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "UMLS_CUI:C0751587" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "cadasil" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "MSH2010_2010_02_22:D046589" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "C499374" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "Notch homolog 3 (Drosophila) protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "NOTCH3 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400718" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400738" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "CADASIL protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "C499374" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17705411", "o": "CADASIL Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17683439", "o": "CADASIL Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12021175", "o": "CADASIL" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6957136", "o": "CADASIL" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CADASIL", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/genes" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CADASIL", "o": "CADASIL" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1802", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CADASIL" } ], "ideal_answer": [ "CADASIL is caused mostly by missense mutations in the NOTCH3 gene, invariably involving a cysteine residue." ], "exact_answer": [ "Cysteine" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046589", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024342", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000596", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.disease-ontology.org/api/metadata/DOID:13945" ], "type": "factoid", "id": "532366f09b2d7acc7e000015", "snippets": [ { "offsetInBeginSection": 5, "offsetInEndSection": 253, "text": "missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, have been described in patients considered to be affected by paucisymptomatic CADASIL. However, the significance of such molecular variants is still unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597439", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 374, "text": "CADASIL is caused mostly by missense mutations in the NOTCH3 gene, invariably involving a cysteine residue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587639", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 302, "text": "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease due to mutations involving loss or gain of a cysteine residue in the NOTCH3 gene. A cluster of mutations around exons 3 and 4 was originally reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21616505", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 521, "text": "The authors report a family with CADASIL carrying a deletion in the Notch3 gene that did not involve a cysteine residue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15304596", "endSection": "abstract" } ] }, { "body": "Which syndromes are associated with mutations in the EZH2 gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21856302", "http://www.ncbi.nlm.nih.gov/pubmed/24507812", "http://www.ncbi.nlm.nih.gov/pubmed/24953053", "http://www.ncbi.nlm.nih.gov/pubmed/10780782", "http://www.ncbi.nlm.nih.gov/pubmed/24218139", "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "http://www.ncbi.nlm.nih.gov/pubmed/24852293", "http://www.ncbi.nlm.nih.gov/pubmed/22177091", "http://www.ncbi.nlm.nih.gov/pubmed/23099237", "http://www.ncbi.nlm.nih.gov/pubmed/25177364", "http://www.ncbi.nlm.nih.gov/pubmed/22475286", "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "http://www.ncbi.nlm.nih.gov/pubmed/22190405", "http://www.ncbi.nlm.nih.gov/pubmed/24760151" ], "ideal_answer": [ "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined. Recent studies have shown that EZH2 mutations are often associated with RUNX1 mutations in MDS patients, although its pathological function remains to be addressed. These data show that mutations in EZH2 cause Weaver syndrome. The EZH2 gene is a homolog of the Drosophila Polycomb group (PcG) gene enhancer of zest, a crucial regulator of homeotic gene expression.", "Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML). Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL). The EZH2 gene is involved in the pathogenesis of 7q35-q36 aberrations in myeloid leukaemia." ], "exact_answer": [ [ "myelodysplastic syndrome (MDS)" ], [ "Acquired aplastic anemia (AA)" ], [ "Weaver syndrome" ], [ "non-Hodgkin lymphoma (NHL)" ], [ "myeloid leukaemia" ] ], "concepts": [ "http://www.uniprot.org/uniprot/EZH2_MACFA", "http://www.uniprot.org/uniprot/EZH2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "list", "id": "57090784cf1c325851000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24953053", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 491, "text": "We describe the use of an oligo-SNP array for genomic profiling of aCNA and cnLOH, together with sequence analysis of recurrently mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with normal karyotype and FISH result", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25177364", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 970, "text": " Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760151", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 967, "text": "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1422, "text": "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "Weaver syndrome and EZH2 mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "title" }, { "offsetInBeginSection": 143, "offsetInEndSection": 237, "text": "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1410, "text": "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Mutations in EZH2 cause Weaver syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177091", "endSection": "title" }, { "offsetInBeginSection": 436, "offsetInEndSection": 496, "text": "These data show that mutations in EZH2 cause Weaver syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177091", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 808, "text": "The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190405", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 963, "text": "EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856302", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 616, "text": "The EZH2 gene was previously reported to be located on chromosome 21q22 and was proposed as a candidate gene for some characteristics of the Down syndrome phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10780782", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 727, "text": "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218139", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 833, "text": "EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475286", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 332, "text": "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 509, "text": "Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24852293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "title" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1107, "text": "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1584, "text": "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 966, "text": "We postulated that mutations in writers of these two chromatin marks could cause overgrowth conditions, resembling Sotos or Weaver syndromes, in patients with no NSD1 or EZH2 abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24852293", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 407, "text": "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099237", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 745, "text": "Recently, the advent of next generation sequencing (NGS) techniques has helped identify somatic gene mutations in 75-80% of MDS, that cluster mainly in four functional groups, i.e. cytokine signaling (RAS genes), DNA methylation, (TET2, IDH1/2, DNMT3a genes) histone modifications (ASXL1 and EZH2 genes), and spliceosome (SF3B1 and SRSF2 genes) along with mutations of RUNX1 and TP 53 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24507812", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1123, "text": "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. NSD1 mutations that cause Sotos syndrome are loss-of-function, primarily truncating mutations or missense mutations at key residues in functional domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 630, "text": "EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475286", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1414, "text": "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 630, "text": "EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475286", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 968, "text": "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 776, "text": "The deletion involved multiple genes, including two tumor suppressor candidate genes (CTNNA1 and HSPA9) that are associated with MDS/AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25177364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099237", "endSection": "abstract" } ] }, { "body": "Which databases exist for experimentally determined topologies of \u03b1-helical transmembrane proteins ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "http://www.ncbi.nlm.nih.gov/pubmed/20601677" ], "ideal_answer": [ "ExTopoDB and TMPDB." ], "exact_answer": [ [ "ExTopoDB" ], [ "TMPDB" ] ], "type": "list", "id": "55414a763f2354b713000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "ExTopoDB: a database of experimentally derived topological models of transmembrane proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 726, "text": "ExTopoDB is a publicly accessible database of experimentally derived topological models of transmembrane proteins. It contains information collected from studies in the literature that report the use of biochemical methods for the determination of the topology of \u03b1-helical transmembrane proteins. Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of \u03b1-helical transmembrane proteins. Topological information is combined with transmembrane topology prediction resulting in more reliable topological models. AVAILABILITY: http://bioinformatics.biol.uoa.gr/ExTopoDB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "TMPDB: a database of experimentally-characterized transmembrane topologies", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 895, "text": "TMPDB is a database of experimentally-characterized transmembrane (TM) topologies. TMPDB release 6.2 contains a total of 302 TM protein sequences, in which 276 are alpha-helical sequences, 17 beta-stranded, and 9 alpha-helical sequences with short pore-forming helices buried in the membrane. The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods. TMPDB would be useful as a test and/or training dataset in improving the proposed TM topology prediction methods or developing novel methods with higher performance, and as a guide for both the bioinformaticians and biologists to better understand TM proteins. TMPDB and its subsets are freely available at the following web site: http://bioinfo.si.hirosaki-u.ac.jp/~TMPDB/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 533, "text": "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of \u0436\u2534-helical transmembrane proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "TMPDB: a database of experimentally-characterized transmembrane topologies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "TMPDB is a database of experimentally-characterized transmembrane (TM) topologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 518, "text": "The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 533, "text": "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of \u03b1-helical transmembrane proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 547, "text": "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of \ufffd-helical transmembrane proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "UNLABELLED: ExTopoDB is a publicly accessible database of experimentally derived topological models of transmembrane proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 521, "text": "The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 534, "text": "Transmembrane protein topology is highly important in order to understand their function and ExTopoDB provides an up to date, complete and comprehensive dataset of experimentally determined topologies of \u03b1-helical transmembrane proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 520, "text": "The TM topologies in TMPDB were determined experimentally by means of X-ray crystallography, NMR, gene fusion technique, substituted cysteine accessibility method, N-linked glycosylation experiment and other biochemical methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "TMPDB is a database of experimentally-characterized transmembrane (TM) topologies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "ExTopoDB: a database of experimentally derived topological models of transmembrane proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "ExTopoDB is a publicly accessible database of experimentally derived topological models of transmembrane proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601677", "endSection": "abstract" } ] }, { "body": "Which disease is characterized by congenital absence of intrinsic ganglion cells of the gastrointestinal tract?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23272425", "http://www.ncbi.nlm.nih.gov/pubmed/16618617", "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "http://www.ncbi.nlm.nih.gov/pubmed/23836442", "http://www.ncbi.nlm.nih.gov/pubmed/10980580", "http://www.ncbi.nlm.nih.gov/pubmed/22184102", "http://www.ncbi.nlm.nih.gov/pubmed/20860806", "http://www.ncbi.nlm.nih.gov/pubmed/16080919", "http://www.ncbi.nlm.nih.gov/pubmed/8401580", "http://www.ncbi.nlm.nih.gov/pubmed/9556633", "http://www.ncbi.nlm.nih.gov/pubmed/22974608", "http://www.ncbi.nlm.nih.gov/pubmed/23043324", "http://www.ncbi.nlm.nih.gov/pubmed/8894691", "http://www.ncbi.nlm.nih.gov/pubmed/22131258", "http://www.ncbi.nlm.nih.gov/pubmed/21656899" ], "ideal_answer": [ "Hirschsprung disease (HSCR, aganglionic megacolon) is a common congenital malformation leading to bowel obstruction, with an incidence of 1/5,000 live births. It is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract. ", "The medical condition characterized by the congenital absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract is called aganlionic megacolon or Hirschsprung disease.", "Hirschsprung disease (HSCR) is a congenital disorder associated with the absence of intrinsic ganglion cells in the distal gastrointestinal tract.This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells.", "Hirschsprungs disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells." ], "exact_answer": [ "Aganlionic megacolon or Hirschsprung disease" ], "type": "factoid", "id": "55000cc4e9bde69634000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Hirschsprung's disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23043324", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 599, "text": "This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23043324", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 162, "text": "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21656899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Hirschsprung disease (HSCR, aganglionic megacolon) is a common congenital malformation leading to bowel obstruction, with an incidence of 1/5,000 live births. It is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Hirschsprung disease (HSCR) is a congenital disorder associated with the absence of intrinsic ganglion cells in the distal gastrointestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8894691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22184102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21656899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Hirschsprung's disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerves forming the plexus of the lower intestine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Hirschsprung disease (HSCR) is an inherited disorder characterised by absence of intrinsic ganglion cells in the distal gastrointestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10980580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8401580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20860806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "BACKGROUND: Hirschsprungs Disease (HD) is a developmental disorder of enteric nervous system characterised by the absence of ganglion cells in submucosal (Meissners) and myenteric (Aurbachs) plexuses of distal bowel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272425", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Hirschsprung's disease is an inherited disorder characterized by the absence of ganglion cells in the distal bowel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16080919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of ganglion cells in various length of distal digestive tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22131258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Hirschsprung disease (HSCR) is a congenital disorder associated with the absence of intrinsic ganglion cells in the distal gastrointestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8894691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Hirschsprung's disease (HSCR) is a congenital intestinal disease, characterized by the absence of ganglion cells in the distal portion of the intestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9556633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intramural ganglion cells along with variable lengths of the gastrointestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22974608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21656899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22184102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Hirschsprung's disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerves forming the plexus of the lower intestine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8401580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20860806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Hirschsprung disease (HSCR) is an inherited disorder characterised by absence of intrinsic ganglion cells in the distal gastrointestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10980580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16618617", "endSection": "abstract" } ] }, { "body": "What is the disease in which patients are sensitive to DNA crosslinking agents, presenting with a high frequency of chromosomal aberrations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20132664", "http://www.ncbi.nlm.nih.gov/pubmed/8876687", "http://www.ncbi.nlm.nih.gov/pubmed/7011307", "http://www.ncbi.nlm.nih.gov/pubmed/7116934", "http://www.ncbi.nlm.nih.gov/pubmed/21568838", "http://www.ncbi.nlm.nih.gov/pubmed/16115458", "http://www.ncbi.nlm.nih.gov/pubmed/8058745" ], "ideal_answer": [ "Fanconi anemia (FA) is an autosomal disorder that causes genome instability and manifests by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations.", "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations. ", "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations." ], "exact_answer": [ "Fanconi anemia" ], "type": "factoid", "id": "54ede28094afd61504000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21568838", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Fanconi anemia (FA) is characterized at the cellular level by a high frequency of spontaneous chromosomal aberrations; crosslinking agents cause an abnormal increase in the frequency of chromosomal damage, and semiconservative DNA synthesis is severely inhibited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8876687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8058745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Cells from patients wtih Fanconi's anemia are unusually sensitive to agents which are capable of crosslinking DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7116934", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 375, "text": "An elevated frequency of chromosome aberrations, which is further exaggerated by exposure of cells to DNA crosslinking agents, is a general feature of Fanconi's anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7116934", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 303, "text": "FA patients exhibit spontaneous chromosome breakage and FA cells are sensitive to DNA interstrand crosslink agents and expresses high frequency of chromosome breakage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20132664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Fanconi anemia (FA) is characterized at the cellular level by a high frequency of spontaneous chromosomal aberrations; crosslinking agents cause an abnormal increase in the frequency of chromosomal damage, and semiconservative DNA synthesis is severely inhibited", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8876687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Cells from patients wtih Fanconi's anemia are unusually sensitive to agents which are capable of crosslinking DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7116934", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 388, "text": "At the cellular level, FA is characterized by hypersensitivity to DNA cross-linking agents and by high frequencies of induced chromosomal aberrations, a property used for diagnosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16115458", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 374, "text": "An elevated frequency of chromosome aberrations, which is further exaggerated by exposure of cells to DNA crosslinking agents, is a general feature of Fanconi's anemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7116934", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1395, "text": "Similarly, Fanconi's anemia cells, which are chromosomally sensitive to crosslinking agents, and appear to be defective in the \"unhooking\" of linked polynucleotide strands [15, 16, 49, 51], are reported to be chromosomally sensitive to ethyl methanesulfonate as well [29], and to be sensitive to ionizing radiation [7, 19, ]0], again implying overlapping repair systems", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7011307", "endSection": "abstract" } ] }, { "body": "How is oprozomib administered?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "http://www.ncbi.nlm.nih.gov/pubmed/22929803", "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "http://www.ncbi.nlm.nih.gov/pubmed/24239172" ], "ideal_answer": [ "Oprozomib is administered orally." ], "exact_answer": [ "Orally" ], "type": "factoid", "id": "56ecfd572ac5ed1459000002", "snippets": [ { "offsetInBeginSection": 715, "offsetInEndSection": 802, "text": "Further, new orally administered second-generation PI oprozomib is being investigated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 254, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 917, "text": "This review provides an overview of the role of oral proteasome inhibitors including Marizomib, Oprozomib, Delanzomib, chemical proteasome inhibitors, and cinnabaramides, in the therapy of MM, focusing on developments over the past five years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24239172", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1071, "text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 882, "text": "Further, new orally administered second-generation PI oprozomib is being investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1414, "text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1365, "text": "We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 716, "text": "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 384, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 800, "text": "Further, new orally administered second-generation PI oprozomib is being investigated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1070, "text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "title" }, { "offsetInBeginSection": 123, "offsetInEndSection": 428, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 543, "text": "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 255, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 802, "text": "new orally administered second-generation PI oprozomib is being investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1072, "text": "including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 428, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1234, "text": "Finally, we found that DC incubation with the drug(s) enhanced I\u03baB expression and that oprozomib inhibited NF-\u03baB expression. We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "endSection": "abstract" } ] }, { "body": "What is a Caveolae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24013648", "http://www.ncbi.nlm.nih.gov/pubmed/23899671", "http://www.ncbi.nlm.nih.gov/pubmed/23727353", "http://www.ncbi.nlm.nih.gov/pubmed/24023653", "http://www.ncbi.nlm.nih.gov/pubmed/23593340", "http://www.ncbi.nlm.nih.gov/pubmed/23340574", "http://www.ncbi.nlm.nih.gov/pubmed/23521716", "http://www.ncbi.nlm.nih.gov/pubmed/23787000", "http://www.ncbi.nlm.nih.gov/pubmed/7407830", "http://www.ncbi.nlm.nih.gov/pubmed/24308657", "http://www.ncbi.nlm.nih.gov/pubmed/23610576", "http://www.ncbi.nlm.nih.gov/pubmed/24013596" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1304410", "o": "4007-0024" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1304410", "o": "caveola intracellularis" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0598071", "o": "http://linkedlifedata.com/resource/umls/label/A1304410" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0598071", "o": "http://linkedlifedata.com/resource/umls/label/A1304410" }, { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0044155", "o": "cellular_component" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0044155", "o": "host caveola" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2752448", "o": "http://linkedlifedata.com/resource/umls/id/C2247081" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14274436", "o": "host cell membrane" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2752448", "o": "http://linkedlifedata.com/resource/umls/label/A17471949" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17471949", "o": "host caveola" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17471949", "o": "Gene Ontology" }, { "p": "http://linkedlifedata.com/resource/geneontology/part_of", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0044155", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0033644" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0033644", "o": "host cell membrane" } ], "ideal_answer": [ "Caveolae, plasma membrane invaginations of 60-80nm in diameter, are a subset of lipid rafts enriched in cholesterol and sphingolipids." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021941", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0072584", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005901", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070836" ], "type": "summary", "id": "54f57892d0d681a040000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Caveolae are flask-shaped plasma membrane invaginations formed by constitutive caveolin proteins and regulatory cavin proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24308657", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 408, "text": "Caveolae are membrane subdomains that function as signaling platforms, endocytic carriers, sensors of membrane tension, and mechanical stress, as well as in lipid homeostasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013596", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 328, "text": "Caveolae are cholesterol-rich microdomains that form mechanically deformable invaginations of the sarcolemma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24023653", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 451, "text": "Caveolae are specialized membrane lipid rafts coated with caveolin scaffolding proteins,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23899671", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 124, "text": " Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects transduced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Caveolae, plasma membrane invaginations of 60-80nm in diameter, are a subset of lipid rafts enriched in cholesterol and sphingolipids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23727353", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 813, "text": "The efficiency of youth is built upon cellular signaling scaffolds that provide tight and coordinated signaling. Lipid rafts are one such scaffold of which caveolae are a subset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23610576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Caveolae are submicroscopic, plasma membrane pits that are abundant in many mammalian cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23340574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Caveolae are non-clathrin invaginations of the plasma membrane in most cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23521716", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 96, "text": "Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Caveolae are an abundant feature of the plasma membrane of many mammalian cell types, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013648", "endSection": "abstract" } ] }, { "body": "Which are the roles of chromatin compartments in the eukaryotic nucleus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15791412", "http://www.ncbi.nlm.nih.gov/pubmed/18974210", "http://www.ncbi.nlm.nih.gov/pubmed/21637796", "http://www.ncbi.nlm.nih.gov/pubmed/15140983", "http://www.ncbi.nlm.nih.gov/pubmed/22198682", "http://www.ncbi.nlm.nih.gov/pubmed/11909528", "http://www.ncbi.nlm.nih.gov/pubmed/9636146", "http://www.ncbi.nlm.nih.gov/pubmed/9291094", "http://www.ncbi.nlm.nih.gov/pubmed/24002784", "http://www.ncbi.nlm.nih.gov/pubmed/9587055", "http://www.ncbi.nlm.nih.gov/pubmed/18434402", "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "http://www.ncbi.nlm.nih.gov/pubmed/11186332" ], "ideal_answer": [ "The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments. Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements. Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Therefore, concentrating proteins needed to perform different steps of RNA synthesis within specialized nuclear compartments is important in orchestrating events required for efficient gene expression." ], "exact_answer": [ [ "providing complex regulation" ], [ "facilitating matching genes and regulatory elements" ], [ "efficient trancription" ] ], "type": "list", "id": "56ebfa13107309bc2f000004", "snippets": [ { "offsetInBeginSection": 1047, "offsetInEndSection": 1242, "text": "concentrating proteins needed to perform different steps of RNA synthesis within specialized nuclear compartments will be important in orchestrating events required for efficient gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9291094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Chromatin domains and nuclear compartments: establishing sites of gene expression in eukaryotic nuclei.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9291094", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 529, "text": "Using the adult bovine lens as a model system, nuclear changes accompanying denucleation are described with particular emphasis on the lamina, nucleolar and coiled body compartments in lens nuclei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9587055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Changes in the nucleolar and coiled body compartments precede lamina and chromatin reorganization during fibre cell denucleation in the bovine lens", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9587055", "endSection": "title" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1419, "text": "Prior to chromatin condensation, coilin redistributed to the nucleolar compartment and was absent from nuclei where chromatin had begun to condense.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9587055", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 876, "text": "These constraints reflect the physical attachment of chromatin to nuclear compartments or steric impairment caused by local ultrastructure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11909528", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 964, "text": "A number of these proteins accumulate in viral replication compartments in the infected cell nucleus, indicating that these proteins may have a role in viral replication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15140983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Nuclear marginalization of host cell chromatin associated with expansion of two discrete virus-induced subnuclear compartments during baculovirus infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434402", "endSection": "title" }, { "offsetInBeginSection": 729, "offsetInEndSection": 898, "text": "In the late stage of infection, however, the peristromal region (PR), another virus-induced subnuclear compartment, was also excluded from the chromatin-localizing area.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434402", "endSection": "abstract" }, { "offsetInBeginSection": 1587, "offsetInEndSection": 1818, "text": "This correlation between compartmentalization and chromatin exclusion suggests the possibility that a chromatin-exclusive property of viral molecules, at least in part, supports nuclear compartmentalization of virus-infected cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Chromatin modifications in hematopoietic multipotent and committed progenitors are independent of gene subnuclear positioning relative to repressive compartments", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974210", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "To further clarify the contribution of nuclear architecture in the regulation of gene expression patterns during differentiation of human multipotent cells, we analyzed expression status, histone modifications, and subnuclear positioning relative to repressive compartments, of hematopoietic loci in multipotent and lineage-committed primary human hematopoietic progenitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974210", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 638, "text": "We report here that positioning of lineage-affiliated loci relative to pericentromeric heterochromatin compartments (PCH) is identical in multipotent cells from various origins and is unchanged between multipotent and lineage-committed hematopoietic progenitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21637796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002784", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002784", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 869, "text": "we find that architectural compartments are maintained in noncycling mouse thymocytes after genetic depletion of cohesin in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002784", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1410, "text": "Our findings indicate that cohesin-mediated long-range interactions facilitate discrete gene expression states within preexisting chromosomal compartments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Histone posttranslational modifications mediate establishment of structurally and functionally distinct chromatin compartments of eukaryotic nuclei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15791412", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 910, "text": "Recent studies employing chromatin conformation capture techniques indicate that Hox clusters adopt a remarkable spatial configuration, in which active and inactive genes are segregated into two distinct chromatin compartments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22198682", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1189, "text": "Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9636146", "endSection": "title" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1940, "text": "We propose that basically three nuclear compartments exist, an "open" higher-order chromatin compartment with chromatin domains containing active genes, a "closed" chromatin compartment comprising inactive genes, and an interchromatin domain (ICD) compartment (Cremer et al., 1993; Zirbel et al., 1993) that contains macromolecular complexes for transcription, splicing, DNA replication, and repair. Genes in "open," but not in "closed" higher-order chromatin compartments have access to transcription and splicing complexes located in the ICD compartment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11186332", "endSection": "abstract" }, { "offsetInBeginSection": 1764, "offsetInEndSection": 2180, "text": "Genes in "open," but not in "closed" higher-order chromatin compartments have access to transcription and splicing complexes located in the ICD compartment. Chromatin domains that build the "open" chromatin compartment are organized in a way that allows the direct contact of genes and nascent RNA to transcription and splicing complexes, respectively, preformed in the ICD compartment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11186332", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1638, "text": "We propose that basically three nuclear compartments exist, an "open" higher-order chromatin compartment with chromatin domains containing active genes, a "closed" chromatin compartment comprising inactive genes, and an interchromatin domain (ICD) compartment (Cremer et al.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11186332", "endSection": "abstract" } ] }, { "body": "Is the abnormal dosage of ultraconserved elements disfavored in cancer cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25340765" ], "ideal_answer": [ "No. Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "yesno", "id": "56c0708eef6e39474100001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 1335, "text": "We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 954, "text": "Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" } ] }, { "body": "Does thyroid hormone regulate calcium transient in the myocardium? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19298522", "http://www.ncbi.nlm.nih.gov/pubmed/9773867", "http://www.ncbi.nlm.nih.gov/pubmed/2428004", "http://www.ncbi.nlm.nih.gov/pubmed/9875761" ], "ideal_answer": [ "YES" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "yesno", "id": "515ac533d24251bc050000a9", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "3-iodothyronamine (T(1)AM) is a novel endogenous relative of thyroid hormone, able to interact with trace amine-associated receptors, a class of plasma membrane G protein-coupled receptors, and to produce a negative inotropic and chronotropic effect", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19298522", "endSection": "sections.0" }, { "offsetInBeginSection": 455, "offsetInEndSection": 580, "text": "In adult rat cardiomyocytes acute exposure to 20 microM T(1)AM decreased the amplitude and duration of the calcium transient.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19298522", "endSection": "sections.0" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1869, "text": "In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9875761", "endSection": "sections.0" }, { "offsetInBeginSection": 2162, "offsetInEndSection": 2428, "text": "The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9773867", "endSection": "sections.0" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1525, "text": "hese results indicate that the thyroid state influences the time course of the calcium transient and are consistent with the abbreviation in the duration of contraction that is observed in the hyperthyroid state.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2428004", "endSection": "sections.0" } ] }, { "body": "What are the biological roles proposed for proteins containing the SPRY domain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22337885", "http://www.ncbi.nlm.nih.gov/pubmed/22872646", "http://www.ncbi.nlm.nih.gov/pubmed/17431422", "http://www.ncbi.nlm.nih.gov/pubmed/23886867", "http://www.ncbi.nlm.nih.gov/pubmed/15857996", "http://www.ncbi.nlm.nih.gov/pubmed/23775985", "http://www.ncbi.nlm.nih.gov/pubmed/16648259", "http://www.ncbi.nlm.nih.gov/pubmed/16226405", "http://www.ncbi.nlm.nih.gov/pubmed/23091002", "http://www.ncbi.nlm.nih.gov/pubmed/21035437", "http://www.ncbi.nlm.nih.gov/pubmed/15689398", "http://www.ncbi.nlm.nih.gov/pubmed/19184407", "http://www.ncbi.nlm.nih.gov/pubmed/16313355", "http://www.ncbi.nlm.nih.gov/pubmed/23139046", "http://www.ncbi.nlm.nih.gov/pubmed/12479811" ], "ideal_answer": [ "defence against retroviral infection\ninnate and adaptative immunity\nvesicular trafficking\nneural differentiation\nembryonic development" ], "exact_answer": [ [ "defence against retroviral infection" ], [ "immunity" ], [ "vesicular trafficking" ], [ "neural differentiation" ], [ "embryonic development" ] ], "concepts": [ "http://www.uniprot.org/uniprot/FBSP1_RAT", "http://www.uniprot.org/uniprot/TRI51_HUMAN", "http://www.uniprot.org/uniprot/FBSP1_DROAN", "http://www.uniprot.org/uniprot/CMYA5_HUMAN", "http://www.uniprot.org/uniprot/FBSP1_DROMO", "http://www.uniprot.org/uniprot/SPRY7_BOVIN", "http://www.uniprot.org/uniprot/SPRY7_RAT", "http://www.uniprot.org/uniprot/FSD1_HUMAN", "http://www.uniprot.org/uniprot/FBSP1_DROPE", "http://www.uniprot.org/uniprot/RSPRY_MOUSE", "http://www.uniprot.org/uniprot/FBSP1_ANOGA", "http://www.uniprot.org/uniprot/FBSP1_BRUMA", "http://www.uniprot.org/uniprot/FBSP1_MOUSE", "http://www.uniprot.org/uniprot/FBSP1_XENLA", "http://www.uniprot.org/uniprot/FBSP1_DROGR", "http://www.uniprot.org/uniprot/SPRY3_PONAB", "http://www.uniprot.org/uniprot/FBSP1_AEDAE", "http://www.uniprot.org/uniprot/FBSP1_HUMAN", "http://www.uniprot.org/uniprot/SPRY3_HUMAN", "http://www.uniprot.org/uniprot/SPSB1_BOVIN", "http://www.uniprot.org/uniprot/SPRY4_HUMAN", "http://www.uniprot.org/uniprot/SPRY7_MOUSE", "http://www.uniprot.org/uniprot/FBSP1_DROSE", "http://www.uniprot.org/uniprot/SPRY7_CHICK", "http://www.uniprot.org/uniprot/SPRY7_HUMAN", "http://www.uniprot.org/uniprot/FSD2_MOUSE", "http://www.uniprot.org/uniprot/RSPRY_MACFA", "http://www.uniprot.org/uniprot/FBSP1_CAEBR", "http://www.uniprot.org/uniprot/SPRY4_MOUSE", "http://www.uniprot.org/uniprot/BSPRY_HUMAN", "http://www.uniprot.org/uniprot/FSD1_DANRE", "http://www.uniprot.org/uniprot/SPSB1_HUMAN", "http://www.uniprot.org/uniprot/BSPRY_MOUSE", "http://www.uniprot.org/uniprot/BSPRY_RAT", "http://www.uniprot.org/uniprot/SPRY4_RAT" ], "type": "list", "id": "533c2230c45e133714000002", "snippets": [ { "offsetInBeginSection": 7, "offsetInEndSection": 141, "text": "monkey TRIM5\u03b1 SPRY domain recognizes multiple epitopes that span several capsid monomers on the surface of the HIV-1 mature viral core", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886867", "endSection": "title" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1033, "text": "These properties, which may enhance resistance of TRIM5\u03b1 to capsid mutations, result in relatively low affinity of the individual SPRY domains for the capsid", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886867", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 180, "text": "RIM5\u03b1 is a retroviral restriction factor, in which the B30.2 (SPRY) and coiled-coil domains cooperate to determine the specificity of TRIM5\u03b1-mediated capture of retroviral capsids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23775985", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 84, "text": "function of the SPRY/B30.2 domain proteins involved in innate immunity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23139046", "endSection": "title" }, { "offsetInBeginSection": 4, "offsetInEndSection": 202, "text": "SPRY domain is a protein interaction module found in 77 murine and ~100 human proteins, and is implicated in important biological pathways, including those that regulate innate and adaptive immunity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23139046", "endSection": "abstract" }, { "offsetInBeginSection": 42, "offsetInEndSection": 136, "text": "TRIM5\u03b1) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23091002", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 257, "text": " TRIM5\u03b1 recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23091002", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 782, "text": "binding of the PRY-SPRY domain from the TRIM50 C-terminal region to phosphatidylinositol species, suggesting that TRIM50 is involved in vesicular dynamics by sensing the phosphorylated state of phosphoinositol lipids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872646", "endSection": "abstract" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1159, "text": "TRIM50 seems to play an essential role in tubulovesicular dynamics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872646", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 988, "text": "TRIM67 regulates Ras signaling via degradation of 80K-H, leading to neural differentiation including neuritogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22337885", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 423, "text": "TRIM67, which has a TRIM motif, an FN3 domain and a SPRY domain, is highly expressed in the cerebellum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22337885", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 468, "text": "Vasa coding region is sufficient for its selective enrichment and find that gustavus, the B30.2/SPRY and SOCS box domain gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035437", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1011, "text": "We propose that Gustavus has a conserved, positive regulatory role in Vasa protein accumulation during embryonic development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035437", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 275, "text": "two zebrafish genes, SSB-1 and SSB-4 (SPRY domain SOCS box proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19184407", "endSection": "abstract" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1063, "text": "We hypothesize that SSB-4 plays a role in the early development of germ cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19184407", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 150, "text": "SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17431422", "endSection": "title" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1290, "text": "TRIM proteins may be conducive to the convergent evolution of virus-restricting factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648259", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 95, "text": "SPRY and B30.2 protein domains. Evolution of a component of immune defence", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16313355", "endSection": "title" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1115, "text": ". The combination of SPRY and PRY to produce B30.2 domains may have been selected and maintained as a component of immune defence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16313355", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 76, "text": " evolution of primate TRIM5alpha, a gene restricting HIV-1 infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16226405", "endSection": "title" }, { "offsetInBeginSection": 433, "offsetInEndSection": 776, "text": "The SPRY domain of TRIM5alpha, which may be responsible for recognition of incoming viral capsids showed higher nonsynonymous/synonymous substitution ratios than the non-SPRY domain, indicating that the adaptive evolution of TRIM5alpha in primates might be an innate strategy developed in defending retrovirus infection during primate evolutio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16226405", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1409, "text": "The results are consistent with a role for TRIM5alpha in innate immunity against retroviruses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15857996", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 70, "text": "B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15857996", "endSection": "title" }, { "offsetInBeginSection": 22, "offsetInEndSection": 109, "text": "primate TRIM5alpha identifies a critical species-specific retroviral restriction domain", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15689398", "endSection": "title" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1426, "text": "By using functional studies of chimeric TRIM5alpha genes, we show that this patch is generally essential for retroviral restriction and is responsible for most of the species-specific antiretroviral restriction activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15689398", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1091, "text": "SPRY protein domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15689398", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 569, "text": "Heterozygotes for gus or a deletion including gus produce embryos with fewer pole cells and posterior patterning defects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12479811", "endSection": "abstract" }, { "offsetInBeginSection": 31, "offsetInEndSection": 85, "text": "SPRY-domain and SOCS-box containing protein, GUSTAVUS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12479811", "endSection": "title" } ] }, { "body": "How could we infer functional associations from gene fusion events?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19582169", "http://www.ncbi.nlm.nih.gov/pubmed/15980440", "http://www.ncbi.nlm.nih.gov/pubmed/16571130", "http://www.ncbi.nlm.nih.gov/pubmed/11438739", "http://www.ncbi.nlm.nih.gov/pubmed/15215406", "http://www.ncbi.nlm.nih.gov/pubmed/22267904", "http://www.ncbi.nlm.nih.gov/pubmed/12095249", "http://www.ncbi.nlm.nih.gov/pubmed/15701682", "http://www.ncbi.nlm.nih.gov/pubmed/18546511", "http://www.ncbi.nlm.nih.gov/pubmed/11178267", "http://www.ncbi.nlm.nih.gov/pubmed/21729286", "http://www.ncbi.nlm.nih.gov/pubmed/17767732", "http://www.ncbi.nlm.nih.gov/pubmed/20532224", "http://www.ncbi.nlm.nih.gov/pubmed/18629289", "http://www.ncbi.nlm.nih.gov/pubmed/23220349", "http://www.ncbi.nlm.nih.gov/pubmed/16221304", "http://www.ncbi.nlm.nih.gov/pubmed/14673105", "http://www.ncbi.nlm.nih.gov/pubmed/20851221", "http://www.ncbi.nlm.nih.gov/pubmed/12429063", "http://www.ncbi.nlm.nih.gov/pubmed/15128449", "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "http://www.ncbi.nlm.nih.gov/pubmed/17597916", "http://www.ncbi.nlm.nih.gov/pubmed/12952538", "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "http://www.ncbi.nlm.nih.gov/pubmed/22161322", "http://www.ncbi.nlm.nih.gov/pubmed/23365410", "http://www.ncbi.nlm.nih.gov/pubmed/12519996", "http://www.ncbi.nlm.nih.gov/pubmed/11820254", "http://www.ncbi.nlm.nih.gov/pubmed/12429059", "http://www.ncbi.nlm.nih.gov/pubmed/12049665", "http://www.ncbi.nlm.nih.gov/pubmed/15960802", "http://www.ncbi.nlm.nih.gov/pubmed/22925561", "http://www.ncbi.nlm.nih.gov/pubmed/11864366", "http://www.ncbi.nlm.nih.gov/pubmed/18081932", "http://www.ncbi.nlm.nih.gov/pubmed/16381848" ], "ideal_answer": [ "The detection of gene fusion events across genomes can be used for the prediction of functional associations of proteins, based on the observation that related proteins in one organism (including physically interacting proteins/members of complexes, proteins involved in the same pathway) tend to be found in other species as a fused composite gene encoding a single multifunctional protein. For this purpose, gene fusion events may be used as the sole evidence or as independent information combined with other 'genome-aware' or similarity-based methods, and functional association may be predicted at different levels. An advantage of this approach is that it is not necessary to know the function of the composite/components to infer association." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050939" ], "type": "summary", "id": "511979b04eab811676000003", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 148, "text": "Gene fusion is an important evolutionary process. It can yield valuable information to infer the interactions and functions of proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23365410", "endSection": "sections.0" }, { "offsetInBeginSection": 424, "offsetInEndSection": 768, "text": "We have developed a Bayesian framework to infer phosphorylation networks from time series measurements of phosphosite concentrations upon ligand stimulation. To increase the prediction accuracy we integrated different types of data, e.g., amino acid sequence data, genomic context data (gene fusion, gene neighborhood, and phylogentic profiles)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22161322", "endSection": "sections.0" }, { "offsetInBeginSection": 174, "offsetInEndSection": 560, "text": "It is assumed that two proteins, which are found to be transcribed by a single transcript in one (or several) genomes are likely to be functionally linked, for example by acting in a same metabolic pathway or by forming a multiprotein complex. This method is of particular interest for studying genes that exhibit no, or only remote, homologies with already well-characterized proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "endSection": "sections.0" }, { "offsetInBeginSection": 469, "offsetInEndSection": 719, "text": "PLEX search results are accompanied by quantitative estimates of linkage confidence, enabling users to take advantage of coinheritance, operon and gene fusion-based methods for inferring gene function and reconstructing cellular systems and pathways.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701682", "endSection": "sections.0" }, { "offsetInBeginSection": 466, "offsetInEndSection": 700, "text": "While phylogenomic profiles remain the central focus of Phydbac2, it now integrates chromosomal proximity and gene fusion analyses as two additional non-similarity-based indicators for inferring pairwise gene functional relationships.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215406", "endSection": "sections.0" }, { "offsetInBeginSection": 34, "offsetInEndSection": 165, "text": "detection of gene fusion events can contribute towards the elucidation of functional associations of proteins within entire genomes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18629289", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Inference of gene function based on gene fusion events: the rosetta-stone method.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 85, "text": "protein domain fusions in human protein interaction networks prediction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851221", "endSection": "title" }, { "offsetInBeginSection": 136, "offsetInEndSection": 410, "text": "Some proteins, involved in a common biological process and encoded by separate genes in one organism, can be found fused within a single protein chain in other organisms. By detecting these triplets, a functional relationship can be established between the unfused proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851221", "endSection": "sections.0" }, { "offsetInBeginSection": 716, "offsetInEndSection": 815, "text": "These results suggest that domain fusion is an appropriate method for predicting protein complexes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851221", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The detection of gene fusion events across genomes can be used for the prediction of functional associations of proteins, including physical interactions or complex formation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18546511", "endSection": "sections.0" }, { "offsetInBeginSection": 394, "offsetInEndSection": 706, "text": "These genomic constraints form the basis for a variety of techniques that employ systematic genome comparisons to predict functional associations among genes. The most powerful techniques to date are based on conserved gene neighborhood, gene fusion events, and common phylogenetic distributions of gene families", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14673105", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "Functional links between proteins can often be inferred from genomic associations between the genes that encode them: groups of genes that are required for the same function tend to show similar species coverage, are often located in close proximity on the genome (in prokaryotes), and tend to be involved in gene-fusion events.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12519996", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Genes linked by fusion events are generally of the same functional category", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11438739", "endSection": "title" }, { "offsetInBeginSection": 53, "offsetInEndSection": 197, "text": "a functional association between two genes can be derived from the existence of a fusion of the two as one continuous sequence in another genome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11438739", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Protein interaction maps for complete genomes based on gene fusion events", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "endSection": "title" }, { "offsetInBeginSection": 760, "offsetInEndSection": 920, "text": "Because there must be selective pressure for certain genes to be fused over the course of evolution, we are able to predict functional associations of proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "endSection": "sections.0" }, { "offsetInBeginSection": 522, "offsetInEndSection": 715, "text": "We observed that gene fusion events are more related to physical interaction between proteins than to other weaker functional relationships such as participation in a common biological pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851221", "endSection": "sections.0" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1058, "text": "FusionDB provides a characterization of a large number of gene fusion events at hand of multiple sequence alignments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "endSection": "sections.0" }, { "offsetInBeginSection": 171, "offsetInEndSection": 283, "text": "Domain fusion analysis has been proposed recently to infer the functional association of the component proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12095249", "endSection": "sections.0" }, { "offsetInBeginSection": 642, "offsetInEndSection": 759, "text": "Here we present a method that identifies gene-fusion events in complete genomes, solely based on sequence comparison.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "endSection": "sections.0" } ] }, { "body": "The protein NONO forms heterodimers. With which proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16148043", "http://www.ncbi.nlm.nih.gov/pubmed/22101825", "http://www.ncbi.nlm.nih.gov/pubmed/22102035", "http://www.ncbi.nlm.nih.gov/pubmed/20421735", "http://www.ncbi.nlm.nih.gov/pubmed/18655028", "http://www.ncbi.nlm.nih.gov/pubmed/19423654", "http://www.ncbi.nlm.nih.gov/pubmed/22416126" ], "ideal_answer": [ "The protein NONO forms heterodimers with PSPC1, SFPQ." ], "exact_answer": [ [ "PSPC1" ], [ "SFPQ" ] ], "concepts": [ "http://www.uniprot.org/uniprot/NONO_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043497", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019281", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055503", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046982" ], "type": "list", "id": "514241fcd24251bc05000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The paraspeckle component 1 (PSPC1) and non-POU-domain-containing octamer-binding protein (NONO) heterodimer is an essential structural component of paraspeckles,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102035", "endSection": "sections.0" }, { "offsetInBeginSection": 117, "offsetInEndSection": 140, "text": "PSPC1-NONO heterodimer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22101825", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Crystallization of a paraspeckle protein PSPC1-NONO heterodimer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102035", "endSection": "title" }, { "offsetInBeginSection": 143, "offsetInEndSection": 409, "text": "difficult heterodimeric complex of two human proteins, paraspeckle component 1 (PSPC1) and non-POU domain-containing octamer-binding protein (NONO), that are involved in gene regulation and the structural integrity of nuclear bodies termed paraspeckles is described.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22101825", "endSection": "sections.0" }, { "offsetInBeginSection": 272, "offsetInEndSection": 495, "text": "SFPQ (PSF) and NONO (p54) are nuclear proteins that interact with each other and have diverse roles in nucleic acids metabolism. The SFPQ/NONO heterodimer was previously found to enhance DNA strand break rejoining in vitro.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20421735", "endSection": "sections.0" }, { "offsetInBeginSection": 181, "offsetInEndSection": 225, "text": "We identified a heterodimer, p54nrb and PSF,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18655028", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16148043", "endSection": "title" }, { "offsetInBeginSection": 402, "offsetInEndSection": 581, "text": "e demonstrated that the PSF heterodimer partner, p54nrb (non-POU-domain-containing, octamer binding protein), can also function as a transcription corepressor, independent of PSF.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19423654", "endSection": "sections.0" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1080, "text": "The PSPC1/NONO heterodimer has a right-handed antiparallel coiled-coil", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22416126", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Structure of the heterodimer of human NONO and paraspeckle protein component 1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22416126", "endSection": "title" } ] }, { "body": "Which syndrome is associated with mutant DVL1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25817014", "http://www.ncbi.nlm.nih.gov/pubmed/25817016" ], "ideal_answer": [ "Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome." ], "exact_answer": [ "Robinow syndrome" ], "type": "factoid", "id": "5709ee36cf1c32585100001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817014", "endSection": "title" }, { "offsetInBeginSection": 311, "offsetInEndSection": 525, "text": "Here, we identified de novo frameshift mutations in DVL1, a mediator of both canonical and non-canonical Wnt signaling, as the cause of RS-OS, an RS subtype involving osteosclerosis, in three unrelated individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817016", "endSection": "title" }, { "offsetInBeginSection": 634, "offsetInEndSection": 784, "text": "argeted Sanger sequencing in additional subjects with DRS uncovered DVL1 exon 14 mutations in five individuals, including a pair of monozygotic twins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817016", "endSection": "abstract" } ] }, { "body": "Are proteasome inhibitors good candidates for treatment of leukemia and solid tumors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22057347", "http://www.ncbi.nlm.nih.gov/pubmed/17145882", "http://www.ncbi.nlm.nih.gov/pubmed/22012631", "http://www.ncbi.nlm.nih.gov/pubmed/15169797", "http://www.ncbi.nlm.nih.gov/pubmed/20160034", "http://www.ncbi.nlm.nih.gov/pubmed/20219102", "http://www.ncbi.nlm.nih.gov/pubmed/19712963", "http://www.ncbi.nlm.nih.gov/pubmed/17431003", "http://www.ncbi.nlm.nih.gov/pubmed/19821999", "http://www.ncbi.nlm.nih.gov/pubmed/22134540", "http://www.ncbi.nlm.nih.gov/pubmed/23477519", "http://www.ncbi.nlm.nih.gov/pubmed/16135477", "http://www.ncbi.nlm.nih.gov/pubmed/23181572", "http://www.ncbi.nlm.nih.gov/pubmed/22353937", "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "http://www.ncbi.nlm.nih.gov/pubmed/12171876" ], "ideal_answer": [ "Yes, several compounds that inhibit different members of the proteasome pathway (for example Bortezomib) are on trial for treatment of leukemia and solid tumors. It seems that a combination with other drugs may be a useful therapy for solid tumors." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061988", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007938" ], "type": "yesno", "id": "517179718ed59a060a00000e", "snippets": [ { "offsetInBeginSection": 824, "offsetInEndSection": 1115, "text": "We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22057347", "endSection": "sections.0" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1464, "text": "We further found that ATO targets AME via both myelodysplastic syndrome 1 (MDS1) and EVI1 moieties and degrades EVI1 via the ubiquitin-proteasome pathway and MDS1 in a proteasome-independent manner. Our results suggest that ATO could be used as a part of targeted therapy for AME-, AML1/MDS1-, MDS1/EVI1-, and EVI1-positive human cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17145882", "endSection": "sections.0" }, { "offsetInBeginSection": 315, "offsetInEndSection": 795, "text": "Previously we had shown the synergic effect of bortezomib and thiostrepton in breast cancer cells in vitro, where sub-apoptotic concentrations of both proteasome inhibitors resulted in synergic increase in cell death when combined as a treatment. Here, we administered such a combination to MDA-MB-231 xenograft tumors in vivo, and found that the effect of complementary proteasome inhibitors reduced tumor growth rates more efficiently than compared with when administered alone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22353937", "endSection": "sections.0" }, { "offsetInBeginSection": 1477, "offsetInEndSection": 1678, "text": "Addition of a proteasome inhibitor to anti-hormonal therapy resulted in a clinical benefit rate of 22% in a limited number of patients with endocrine resistant and progressive metastatic breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134540", "endSection": "sections.0" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1288, "text": "Taken together, these data support the clinical development of MLN9708 for both hematologic and solid tumor indications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20160034", "endSection": "sections.0" }, { "offsetInBeginSection": 1584, "offsetInEndSection": 1690, "text": "Bortezomib has minimal activity as a single-agent in the treatment of recurrent platinum-sensitive EOC/PPC", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712963", "endSection": "sections.0" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1762, "text": "Our study indicates a molecular mechanism by which the sensitivity of thyroid cancer cells is regulated by the level of GRP78 as well as preferential induction of GRP78 or CHOP upon treatment with proteasome inhibitors. Our experiments therefore suggest a novel approach toward sensitization of thyroid cancer cells to proteasome inhibitors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17431003", "endSection": "sections.0" }, { "offsetInBeginSection": 1270, "offsetInEndSection": 1511, "text": "Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16135477", "endSection": "sections.0" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1709, "text": "The maximum-tolerated dose and recommended phase II dose of bortezomib in this schedule is 1.6 mg/m(2). Biologic activity (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is seen in AIPCa at tolerated doses of bortezomib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15169797", "endSection": "sections.0" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1278, "text": "Given the results of this trial, it is safe and reasonable to recommend treatment with PS341 on the schedule used in this trial at 1.56 mg/m2/dose in Phase II trials. Particular care should be taken with patients with preexisting neuropathy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171876", "endSection": "sections.0" }, { "offsetInBeginSection": 518, "offsetInEndSection": 647, "text": "The successes of proteasome inhibitors in MM are now being translated to other hematologic malignancies, including acute leukemia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23477519", "endSection": "sections.0" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1048, "text": "Such efforts have led to bortezomib, the first FDA approved proteasome inhibitor now used as a frontline treatment for newly diagnosed multiple myeloma (MM), relapsed/refractory MM and mantle cell lymphoma", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23181572", "endSection": "sections.0" }, { "offsetInBeginSection": 383, "offsetInEndSection": 696, "text": "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "sections.0" } ] }, { "body": "Is there any link between CTF4 and CTF18 during sister chromatid cohesion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "http://www.ncbi.nlm.nih.gov/pubmed/17483413", "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "http://www.ncbi.nlm.nih.gov/pubmed/19430531", "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "http://www.ncbi.nlm.nih.gov/pubmed/14742714", "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "http://www.ncbi.nlm.nih.gov/pubmed/23036200" ], "ideal_answer": [ "Yes. CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. Absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045876", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007062", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007063" ], "type": "yesno", "id": "553cae13f32186855800000e", "snippets": [ { "offsetInBeginSection": 1152, "offsetInEndSection": 1292, "text": "Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19430531", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 880, "text": "These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17483413", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 1082, "text": "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks. The ring-shaped cohesin complex is loaded onto chromosomes before S phase in an ATP hydrolysis-dependent reaction. Cohesion establishment during DNA replication follows without further cohesin recruitment and without need for cohesin to re-engage an ATP hydrolysis motif that is critical for its initial DNA binding. This provides evidence for cohesion establishment in the context of replication forks and imposes constraints on the mechanism involved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "title" }, { "offsetInBeginSection": 199, "offsetInEndSection": 430, "text": "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 810, "text": "We also show that, in contrast to mitosis, RF-C(Ctf18/Dcc1/Cft8), Ctf4 and Chl1 are essential for chromosome segregation during meiosis and for the viability of meiotic products.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 614, "text": "Ctf8p is a component of Ctf18-RFC, an alternative replication factor C-like complex required for efficient sister chromatid cohesion in Saccharomyces cerevisiae. We performed synthetic genetic array (SGA) analysis with a ctf8 deletion strain as a primary screen to identify other nonessential genes required for efficient sister chromatid cohesion. We then assessed proficiency of cohesion at three chromosomal loci in strains containing deletions of the genes identified in the ctf8 SGA screen. Deletion of seven genes (CHL1, CSM3, BIM1, KAR3, TOF1, CTF4, and VIK1) resulted in defective sister chromatid cohesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14742714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 587, "text": "CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1452, "text": "The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 626, "text": "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "title" }, { "offsetInBeginSection": 140, "offsetInEndSection": 324, "text": "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 430, "text": "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 584, "text": "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "title" }, { "offsetInBeginSection": 629, "offsetInEndSection": 858, "text": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036200", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 587, "text": "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 629, "text": "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 326, "text": "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 431, "text": "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 628, "text": "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 586, "text": "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 325, "text": "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 831, "text": "In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" } ] }, { "body": "What is the Genomic Regions Enrichment of Annotations Tool (GREAT)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20436461" ], "ideal_answer": [ "Genomic Regions Enrichment of Annotations Tool (GREAT) is a tool to analyse the functional significance of cis-regulatory regions identified by localised measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions. GREAT incorporates annotations from 20 ontologies and is available as a web application. Applying GREAT to data sets from chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) of multiple transcription-associated factors, including SRF, NRSF, GABP, Stat3 and p300 in different developmental contexts, many functions of these factors are recovered that are missed by existing gene-based tools, and testable hypotheses are generated. The utility of GREAT is not limited to ChIP-seq, as it could also be applied to open chromatin, localized epigenomic markers and similar functional data sets, as well as comparative genomics sets." ], "type": "summary", "id": "56a7d5afa17756b72f000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 439, "text": "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436461", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 1093, "text": " GREAT incorporates annotations from 20 ontologies and is available as a web application. Applying GREAT to data sets from chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) of multiple transcription-associated factors, including SRF, NRSF, GABP, Stat3 and p300 in different developmental contexts, we recover many functions of these factors that are missed by existing gene-based tools, and we generate testable hypotheses. The utility of GREAT is not limited to ChIP-seq, as it could also be applied to open chromatin, localized epigenomic markers and similar functional data sets, as well as comparative genomics sets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": " We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436461", "endSection": "abstract" } ] }, { "body": "What is the target of the drug Olaparib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25221646", "http://www.ncbi.nlm.nih.gov/pubmed/25120693", "http://www.ncbi.nlm.nih.gov/pubmed/25139258", "http://www.ncbi.nlm.nih.gov/pubmed/25417706", "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "http://www.ncbi.nlm.nih.gov/pubmed/25275045", "http://www.ncbi.nlm.nih.gov/pubmed/25302833", "http://www.ncbi.nlm.nih.gov/pubmed/25144364", "http://www.ncbi.nlm.nih.gov/pubmed/25531448", "http://www.ncbi.nlm.nih.gov/pubmed/25218906", "http://www.ncbi.nlm.nih.gov/pubmed/25481791", "http://www.ncbi.nlm.nih.gov/pubmed/25128455", "http://www.ncbi.nlm.nih.gov/pubmed/25526472", "http://www.ncbi.nlm.nih.gov/pubmed/25483710", "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "http://www.ncbi.nlm.nih.gov/pubmed/25374341" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17682038", "o": "C71721" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2316164", "o": "http://linkedlifedata.com/resource/umls/label/A17696481" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17696481", "o": "Olaparib" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2316164", "o": "http://linkedlifedata.com/resource/umls/label/A17682038" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17682038", "o": "PARP Inhibitor AZD2281" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17696481", "o": "C71721" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17682038", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17696481", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#inScheme", "s": "http://linkedlifedata.com/resource/umls/id/C2316164", "o": "http://linkedlifedata.com/resource/umls" } ], "ideal_answer": [ "The drug Olaparib target the protein poly(ADP-ribose) polymerase." ], "exact_answer": [ "poly(ADP-ribose) polymerase", "PARP" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011065", "http://www.uniprot.org/uniprot/PARP_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042493", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364", "http://www.uniprot.org/uniprot/PARP_SARPE" ], "type": "factoid", "id": "54d649843706e89528000009", "snippets": [ { "offsetInBeginSection": 97, "offsetInEndSection": 168, "text": "We show that targeting PARP by the small molecule inhibitors, Olaparib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531448", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 774, "text": "Following treatment with the PARP1 inhibitor olaparib, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25526472", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 111, "text": "the PARP inhibitor olaparib", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Olaparib (AZD-2281, Ku-0059436) is an orally bioavailable and well-tolerated poly(ADP-ribose) polymerase (PARP) inhibitor currently under investigation in patients with solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483710", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 62, "text": "The poly(ADP-ribose) polymerase inhibitor olaparib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25481791", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 569, "text": "olaparib (poly(ADP ribose)polymerase inhibitor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25417706", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 282, "text": " olaparib, a PARP inhibitor, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25374341", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 67, "text": "Olaparib is an oral poly (ADP-ribose) polymerase inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 826, "text": "olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25302833", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 363, "text": "he poly (ADP-ribose) polymerase inhibitor olaparib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25275045", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1468, "text": " PARP-inhibitor, Olaparib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25221646", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 63, "text": "Olaparib is a poly(ADP-ribose) polymerase inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218906", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1045, "text": "olaparib, a specific PARP1 inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25144364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 24, "text": "PARP inhibitor olaparib ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25139258", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 603, "text": "We used two PARP inhibitors in clinical development, olaparib and rucaparib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25128455", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 673, "text": " the PARPi, olaparib, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "endSection": "abstract" } ] }, { "body": "Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23633213", "http://www.ncbi.nlm.nih.gov/pubmed/17906375", "http://www.ncbi.nlm.nih.gov/pubmed/7913092", "http://www.ncbi.nlm.nih.gov/pubmed/9092799", "http://www.ncbi.nlm.nih.gov/pubmed/17040361", "http://www.ncbi.nlm.nih.gov/pubmed/7711514", "http://www.ncbi.nlm.nih.gov/pubmed/8068885", "http://www.ncbi.nlm.nih.gov/pubmed/12750454", "http://www.ncbi.nlm.nih.gov/pubmed/15913586", "http://www.ncbi.nlm.nih.gov/pubmed/9685218", "http://www.ncbi.nlm.nih.gov/pubmed/15988389", "http://www.ncbi.nlm.nih.gov/pubmed/9350446", "http://www.ncbi.nlm.nih.gov/pubmed/8954015", "http://www.ncbi.nlm.nih.gov/pubmed/8115332", "http://www.ncbi.nlm.nih.gov/pubmed/8594618", "http://www.ncbi.nlm.nih.gov/pubmed/8384535", "http://www.ncbi.nlm.nih.gov/pubmed/15860414", "http://www.ncbi.nlm.nih.gov/pubmed/8475937", "http://www.ncbi.nlm.nih.gov/pubmed/12356724" ], "ideal_answer": [ "The lack of TR alpha1 exacerbates the manifestation of RTH in TR betaPV mice. Therefore, TR alpha1 could play a compensatory role in mediating the functions of T3 in heterozygous patients with RTH" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018382", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.disease-ontology.org/api/metadata/DOID:11633", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988" ], "type": "yesno", "id": "52f7c4bd2059c6d71c00002d", "snippets": [ { "offsetInBeginSection": 1376, "offsetInEndSection": 1525, "text": "This study reports the consequences of LT4 treatment over a prolonged period of time in 2 of the first patients with a heterozygous mutation in TR\u03b11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633213", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 937, "text": "Here we show that the dysregulation of the pituitary-thyroid axis was worsened by the lack of TR alpha1 in TR betaPV mice, and severe impairment of postnatal growth was manifested in TR betaPV mice deficient in TR alpha1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12750454", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 556, "text": "Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12356724", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1171, "text": "The data demonstrate a novel array of effects mediated by a dominant negative TRalpha1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12356724", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1049, "text": "No mutations in DNA- and hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, suggesting that the defect could be due to an unknown mutation in either the TR gene or a post receptor abnormality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17906375", "endSection": "abstract" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1285, "text": "These results demonstrate that the lack of TR alpha1 exacerbates the manifestation of RTH in TR betaPV mice. Therefore, TR alpha1 could play a compensatory role in mediating the functions of T3 in heterozygous patients with RTH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12750454", "endSection": "abstract" } ] }, { "body": "What is the role of RhoA in bladder cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19896475", "http://www.ncbi.nlm.nih.gov/pubmed/21054792", "http://www.ncbi.nlm.nih.gov/pubmed/12855641", "http://www.ncbi.nlm.nih.gov/pubmed/22006759", "http://www.ncbi.nlm.nih.gov/pubmed/18190825" ], "ideal_answer": [ "In urinary bladder cancer, RhoA was more commonly found to be activated in the later stages of the disease. This activation was related to poor tumor differentiation, muscle invasion, lymph node metastasis, and shortened disease-free and overall survival." ], "concepts": [ "http://www.uniprot.org/uniprot/RHOA_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001749", "http://www.disease-ontology.org/api/metadata/DOID:4007", "http://www.disease-ontology.org/api/metadata/DOID:11054", "http://www.disease-ontology.org/api/metadata/DOID:7371" ], "type": "summary", "id": "53188c12b166e2b80600001a", "snippets": [ { "offsetInBeginSection": 1238, "offsetInEndSection": 1382, "text": "Alterations in RhoA, RhoB, RhoC, Rac1 and Cdc42 expression play a significant role in the genesis and progression of UCC of the urinary bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22006759", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 951, "text": "Published reports suggest that elevated RhoA/Rho-kinase signaling plays a role in the development of benign prostatic hyperplasia, erectile dysfunction, kidney failure, ejaculation disorders, prostate and bladder cancer initiation, and eventual metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21054792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The suppressive effect of Rho kinase inhibitor, Y-27632, on oncogenic Ras/RhoA induced invasion/migration of human bladder cancer TSGH cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19896475", "endSection": "title" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1410, "text": "Our results provide evidence that Ras-induced RhoA and NF-kappaB activation was involved in the invasion/migration of bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19896475", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1075, "text": "Increased RHOA expression was more common in grade 3 than in grade 2 tumors (P = 0.016).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18190825", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 674, "text": "RhoA, RhoC, and ROCK were more abundant in tumors and metastatic lymph nodes than in nontumor bladder and uninvolved lymph nodes (P < 0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12855641", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 986, "text": "High RhoA, RhoC, and ROCK expression were related to poor tumor differentiation (P < 0.05, P < 0.01, and P < 0.01, respectively), muscle invasion (P < 0.001), and lymph node metastasis (P < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12855641", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1118, "text": "Kaplan-Meier plots linked high RhoA, RhoC, and ROCK protein expression to shortened disease-free and overall survival (P < 0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12855641", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1255, "text": "By univariate analysis, high RhoA, RhoC, and ROCK protein expression predicted shortened disease-free and overall survival (P < 0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12855641", "endSection": "abstract" }, { "offsetInBeginSection": 1690, "offsetInEndSection": 1890, "text": "Overall survival in tumors invading muscle (T2 to T4; 44 patients) was significantly influenced by RhoA, RhoC, and ROCK in a Kaplan-Meier analysis (P < 0.0001, P < 0.0001, and P < 0.01, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12855641", "endSection": "abstract" } ] }, { "body": "List human proteins that are subject to a dimer-to-tetramer transition.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23739980", "http://www.ncbi.nlm.nih.gov/pubmed/21080238", "http://www.ncbi.nlm.nih.gov/pubmed/25548170", "http://www.ncbi.nlm.nih.gov/pubmed/25619277", "http://www.ncbi.nlm.nih.gov/pubmed/21987805" ], "ideal_answer": [ "GAC\nSHMT2\nAMPAR\nOrai1\nOrai3" ], "exact_answer": [ [ "GAC" ], [ "SHMT2" ], [ "AMPAR" ], [ "Orai1" ], [ "Orai3" ] ], "type": "list", "id": "56f802ea09dd18d46b000017", "snippets": [ { "offsetInBeginSection": 850, "offsetInEndSection": 946, "text": " the ability of GAC to undergo the dimer-to-tetramer transition necessary for enzyme activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25548170", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1600, "text": "while SHMT2 undergoes a dimer-to-tetramer transition upon PLP binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25619277", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1364, "text": "AMPARs that is required for the critical dimer-to-tetramer transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739980", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1319, "text": "We conclude that the human Orai1 and Orai3 channels undergo a dimer-to-tetramer transition to form a Ca(2+)-selective pore during store-operated activation and that Orai3 forms a dimeric nonselective cation pore upon activation by 2-APB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21987805", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 697, "text": "the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21080238", "endSection": "abstract" } ] }, { "body": "Inhibition of which transporter is the mechanism of action of drug Canagliflozin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24040872", "http://www.ncbi.nlm.nih.gov/pubmed/24025022", "http://www.ncbi.nlm.nih.gov/pubmed/22621689", "http://www.ncbi.nlm.nih.gov/pubmed/21680987", "http://www.ncbi.nlm.nih.gov/pubmed/23590413", "http://www.ncbi.nlm.nih.gov/pubmed/24257692", "http://www.ncbi.nlm.nih.gov/pubmed/23087012", "http://www.ncbi.nlm.nih.gov/pubmed/22547464", "http://www.ncbi.nlm.nih.gov/pubmed/23895803", "http://www.ncbi.nlm.nih.gov/pubmed/10481836", "http://www.ncbi.nlm.nih.gov/pubmed/23563279", "http://www.ncbi.nlm.nih.gov/pubmed/23042029", "http://www.ncbi.nlm.nih.gov/pubmed/23412078", "http://www.ncbi.nlm.nih.gov/pubmed/23729000", "http://www.ncbi.nlm.nih.gov/pubmed/23326927" ], "ideal_answer": [ "Inhibition of sodium glucose co-transporter 2 (SGLT2) is the major mechanism of action of canagliflozin. Canagliflozin is the first SGLT2 inhibitor to be approved in the USA for the treatment of type 2 diabetes and is under regulatory review in the EU. Other SGLT2 inhibitors include dapagliflozin and empagliflozin." ], "exact_answer": [ "sodium glucose co-transporter 2" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051051", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032410", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ], "type": "factoid", "id": "5335c7f2d6d3ac6a34000051", "snippets": [ { "offsetInBeginSection": 303, "offsetInEndSection": 436, "text": "During the past year, two SGLT2 inhibitors, canagliflozin and dapagliflozin, have been approved for the treatment of type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257692", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 955, "text": "Currently dapagliflozin, one of the three most advanced SGLT2 inhibitors in the development (along with canagliflozin and empagliflozin), is already in the market in few European countries and canagliflozin has been approved from the Food and Drug Administration (FDA) in US.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Sodium glucose co-transporter 2 (SGLT2) inhibition with canagliflozin in type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025022", "endSection": "title" }, { "offsetInBeginSection": 429, "offsetInEndSection": 636, "text": "This report reviews the potentially beneficial effects of SGLT2 inhibitors in type 2 diabetes mellitus, specifically focusing on canagliflozin, the only SGLT2 inhibitor approved for use in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025022", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 290, "text": "The sodium glucose co-transporter 2 inhibitor canagliflozin lowered blood glucose, blood pressure, and body weight, with increased risk of urogenital infections in Phase 2 studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23895803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Canagliflozin (Invokana\u2122), an oral selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, is under global development with Mitsubishi Tanabe Pharma and Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson, for the treatment of type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729000", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 780, "text": "Canagliflozin is the first SGLT2 inhibitor to be approved in the USA and is under regulatory review in the EU. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Canagliflozin , an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23590413", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 141, "text": "Canagliflozin is an orally administered sodium glucose cotransporter 2 inhibitor proposed for the treatment of type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23590413", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 665, "text": "In this review, we summarize recent animal and human studies on ipragliflozin and other SGLT2 inhibitors including dapagliflozin, canagliflozin, empagliflozin, tofogliflozin, and luseogliflozin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23563279", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 116, "text": "Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23412078", "endSection": "abstract" }, { "offsetInBeginSection": 1665, "offsetInEndSection": 1834, "text": "Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23412078", "endSection": "abstract" } ] }, { "body": "What is the prognostic role of thyroid hormone in patients with heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15642542", "http://www.ncbi.nlm.nih.gov/pubmed/12963854", "http://www.ncbi.nlm.nih.gov/pubmed/17315395", "http://www.ncbi.nlm.nih.gov/pubmed/15694896", "http://www.ncbi.nlm.nih.gov/pubmed/2189307", "http://www.ncbi.nlm.nih.gov/pubmed/20024637", "http://www.ncbi.nlm.nih.gov/pubmed/19110971", "http://www.ncbi.nlm.nih.gov/pubmed/18221125", "http://www.ncbi.nlm.nih.gov/pubmed/22870736", "http://www.ncbi.nlm.nih.gov/pubmed/23369135", "http://www.ncbi.nlm.nih.gov/pubmed/19181292", "http://www.ncbi.nlm.nih.gov/pubmed/2358611", "http://www.ncbi.nlm.nih.gov/pubmed/16499159", "http://www.ncbi.nlm.nih.gov/pubmed/15259379", "http://www.ncbi.nlm.nih.gov/pubmed/19917524", "http://www.ncbi.nlm.nih.gov/pubmed/8333797", "http://www.ncbi.nlm.nih.gov/pubmed/17966446", "http://www.ncbi.nlm.nih.gov/pubmed/8960429", "http://www.ncbi.nlm.nih.gov/pubmed/23435988", "http://www.ncbi.nlm.nih.gov/pubmed/17923583", "http://www.ncbi.nlm.nih.gov/pubmed/20978564", "http://www.ncbi.nlm.nih.gov/pubmed/12165115", "http://www.ncbi.nlm.nih.gov/pubmed/23555069", "http://www.ncbi.nlm.nih.gov/pubmed/9489964", "http://www.ncbi.nlm.nih.gov/pubmed/17893267", "http://www.ncbi.nlm.nih.gov/pubmed/19006851" ], "ideal_answer": [ "Altered thyroid profile, particularly sick euthyroid syndrome, is an independent predictor of mortality in patients with chronic heart failure, adding prognostic information to conventional clinical and functional cardiac parameters." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005067", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.disease-ontology.org/api/metadata/DOID:9651", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143" ], "type": "summary", "id": "531b2fc3b166e2b80600003c", "snippets": [ { "offsetInBeginSection": 1115, "offsetInEndSection": 1429, "text": " Cumulative survival was significantly lower among patients with free triiodothyronine < 2.12 pg/mL and among patients with brain natriuretic peptide > 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978564", "endSection": "abstract" }, { "offsetInBeginSection": 1261, "offsetInEndSection": 1430, "text": "The T3 was more meaningful than the BNP in the prognosis of CHF. The BNP and T3 combination detection was more valuable in determining the severity of CHF and prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870736", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1679, "text": "fT3 and BNP hold an independent and additive prognostic value in HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19181292", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1177, "text": "Univariate regression analysis showed that TSH (p<0.0001), fT3 (p<0.0001), fT4 (p=0.016) and fT3/fT4 (p<0.0001) were associated with heart failure progression but multivariate analysis showed that only TSH considered as a continuous variable (p = 0.001) as well as subclinical hypothyroidism (TSH > 5.5 mUI/l; p=0.014) remained significantly associated with the events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19006851", "endSection": "abstract" }, { "offsetInBeginSection": 1816, "offsetInEndSection": 2003, "text": "Low T(3) levels are an independent predictor of mortality in patients with chronic heart failure, adding prognostic information to conventional clinical and functional cardiac parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15694896", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1181, "text": "Sixteen patients (14%) died during the follow-up period; their fT3/fT4 ratio was significantly lower than the patients who survived (1.31+/-0.37 vs. 2.01+/-0.72, p<0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15642542", "endSection": "abstract" }, { "offsetInBeginSection": 1549, "offsetInEndSection": 1717, "text": "The authors conclude that among elderly patients with heart failure, lower triiodothyronine concentrations are more prevalent and are associated with a worse prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12963854", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1190, "text": "A low free T3 index/reverse T3 ratio is associated with poor ventricular function and nutritional status and is the strongest predictor yet identified for short-term outcome in patients with advanced heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2358611", "endSection": "abstract" } ] }, { "body": "which mutations of phospholamban gene have been found to cause hypertrophic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17655857", "http://www.ncbi.nlm.nih.gov/pubmed/21167350", "http://www.ncbi.nlm.nih.gov/pubmed/16829191", "http://www.ncbi.nlm.nih.gov/pubmed/12705874" ], "ideal_answer": [ "The following mutations of the phospholamban gene have been found to be associated with hypertrophic cardiomyopathy: PLN L39X nonsense mutation; PLN Leu39Ter; PLN -42 C>G and PLN -77A-->G" ], "exact_answer": [ [ "PLN L39X nonsense mutation" ], [ "PLN Leu39Ter" ], [ "PLN -42 C>G" ], [ "PLN -77A-->G" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.uniprot.org/uniprot/PPLA_CANFA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "list", "id": "531376c8e3eabad021000012", "snippets": [ { "offsetInBeginSection": 840, "offsetInEndSection": 1095, "text": "one L39X nonsense mutation was identified in 1 of 1,064 HCM proband cases with a family history of HCM, previously found to be negative for the current HCM genetic test panel. This mutation cosegregated with incidence of HCM in a multigenerational family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21167350", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 848, "text": "The PLN -42 C>G mutation was found in one patient with late onset familial apical hypertrophic cardiomyopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16829191", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1353, "text": "The PLN -42 C>G mutation is associated with a benign form of apical hypertrophic cardiomyopathy in this family, though the presence of a healthy adult carrier suggests that other genetic and environmental factors could be involved. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16829191", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 692, "text": "We found a heterozygous single nucleotide transition from A to G at -77-bp upstream of the transcription start site in the phospholamban promoter region of one patient with familial hypertrophic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12705874", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 1066, "text": "Using neonatal rat cardiomyocytes, the mutation, -77A-->G, increased the phospholamban promoter activity. No nucleotide change in the phospholamban coding region was found in 99 patients with cardiomyopathy. We suspect that the mutation plays an important role in the development of hypertrophic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12705874", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1025, "text": "Two novel mutations in the CALR3 gene were identified (Lys82Arg, Arg73Gln) and one truncation mutation in the PLN gene (Leu39Ter). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17655857", "endSection": "abstract" } ] }, { "body": "Which gene strand is targeted by transcription-coupled repair (TCR)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18817898", "http://www.ncbi.nlm.nih.gov/pubmed/8807287", "http://www.ncbi.nlm.nih.gov/pubmed/12142466", "http://www.ncbi.nlm.nih.gov/pubmed/10637337", "http://www.ncbi.nlm.nih.gov/pubmed/9637246", "http://www.ncbi.nlm.nih.gov/pubmed/11821423", "http://www.ncbi.nlm.nih.gov/pubmed/15380101", "http://www.ncbi.nlm.nih.gov/pubmed/7957102", "http://www.ncbi.nlm.nih.gov/pubmed/9288788", "http://www.ncbi.nlm.nih.gov/pubmed/15249207", "http://www.ncbi.nlm.nih.gov/pubmed/17893751", "http://www.ncbi.nlm.nih.gov/pubmed/22902626", "http://www.ncbi.nlm.nih.gov/pubmed/20463888", "http://www.ncbi.nlm.nih.gov/pubmed/11182543", "http://www.ncbi.nlm.nih.gov/pubmed/15913669", "http://www.ncbi.nlm.nih.gov/pubmed/17015469", "http://www.ncbi.nlm.nih.gov/pubmed/14599741", "http://www.ncbi.nlm.nih.gov/pubmed/14599769", "http://www.ncbi.nlm.nih.gov/pubmed/9065408", "http://www.ncbi.nlm.nih.gov/pubmed/8972850", "http://www.ncbi.nlm.nih.gov/pubmed/9934845", "http://www.ncbi.nlm.nih.gov/pubmed/16158195", "http://www.ncbi.nlm.nih.gov/pubmed/18291710", "http://www.ncbi.nlm.nih.gov/pubmed/9150262", "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "http://www.ncbi.nlm.nih.gov/pubmed/21466822", "http://www.ncbi.nlm.nih.gov/pubmed/16394029", "http://www.ncbi.nlm.nih.gov/pubmed/15186415", "http://www.ncbi.nlm.nih.gov/pubmed/21214942", "http://www.ncbi.nlm.nih.gov/pubmed/11452033", "http://www.ncbi.nlm.nih.gov/pubmed/20978633", "http://www.ncbi.nlm.nih.gov/pubmed/19381941", "http://www.ncbi.nlm.nih.gov/pubmed/16978026", "http://www.ncbi.nlm.nih.gov/pubmed/14734564", "http://www.ncbi.nlm.nih.gov/pubmed/12509290" ], "ideal_answer": [ "Nucleotide Excision Repair (NER) removes a variety of helix-distorting lesions from DNA. It has two sub-pathways, the global genome (gg) NER and the transcription-coupled repair (TCR). TCR is triggered when a RNA polymerase, translocating along the transcribed strand, is arrested at a lesion or unusual structure in the DNA. TCR is dedicated to target and repair the transcribed strand of an active gene." ], "exact_answer": [ "the transcribed strand" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090262", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052416", "http://www.uniprot.org/uniprot/MFD_STAAM", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006283" ], "type": "factoid", "id": "5545186cbf90a13052000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Transcription-coupled repair (TCR) is the major pathway involved in the removal of UV-induced photolesions from the transcribed strand of active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22902626", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 641, "text": "transcription-coupled repair (TCR) provides faster repair of the transcribed strand of active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21466822", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 362, "text": "there are two sub-pathways of nucleotide excision repair (NER), the global genome (gg) NER and the transcription-coupled repair (TCR). TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21214942", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 892, "text": "transcription-coupled repair (TCR) since targets for DNA damage are situated on the transcribed or coding strand of DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Nucleotide Excision Repair (NER), which removes a variety of helix-distorting lesions from DNA, is initiated by two distinct DNA damage-sensing mechanisms. Transcription Coupled Repair (TCR) removes damage from the active strand of transcribed genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20463888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair that allows for the enhanced repair of the transcribed strand of active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19381941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Transcription coupled repair (TCR) is a nucleotide excision repair (NER) pathway that is dedicated to repair in the transcribed strand of an active gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18817898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Transcription-coupled repair (TCR) is a pathway dedicated to the removal of damage from the template strands of actively transcribed genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18291710", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 325, "text": "Although the detailed mechanism of TCR is not yet understood, it is believed to be triggered when a translocating RNA polymerase is arrested at a lesion or unusual structure in the DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18291710", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 446, "text": "Among these is a process called transcription-coupled repair (TCR) that catalyzes the removal of DNA lesions from the transcribed strand of expressed genes, often resulting in a preferential bias of damage clearance from this strand relative to its non-transcribed counterpart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12509290", "endSection": "abstract" }, { "offsetInBeginSection": 1427, "offsetInEndSection": 1660, "text": "These results suggest that UV treatment results in an induced repair of UV-damaged DNA in the transcribed strand of an active gene in XP-C and normal cells through an enhancement of TCR or a mechanism which involves the TCR pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9934845", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 349, "text": "TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21214942", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 479, "text": "The proficient repair of the nontranscribed strand cannot be explained by the dedicated subpathway of transcription-coupled repair (TCR), which is targeted to the transcribed strand in expressed genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17015469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Transcription-coupled repair (TCR) is a universal sub-pathway of the nucleotide excision repair (NER) system that is limited to the transcribed strand of active structural genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7957102", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 613, "text": "NER can operate via two subpathways: global genome repair (GGR) and a specialized pathway coupled to active transcription (transcription-coupled repair, TCR) and directed to DNA lesions in the transcribed strand of active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14599769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Transcription coupled repair (TCR), a special sub-pathway of nucleotide excision repair (NER), removes transcription blocking lesions rapidly from the transcribing strand of active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11182543", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 527, "text": "Transcription-coupled repair (TCR) acts solely on the transcribed strand of expressed genes, while global genomic repair (GGR) is responsible for the ubiquitous repair of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16394029", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 496, "text": "In addition to the recognition and excision of DNA damage throughout the genome (GGR), there exists a mechanism, transcription-coupled nucleotide excision repair (TCR), for recognizing some types of DNA damage in the transcribed strand of genes in Escherichia coli, yeast and mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15186415", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 481, "text": "The proficient repair of the nontranscribed strand cannot be explained by the dedicated subpathway of transcription-coupled repair (TCR), which is targeted to the transcribed strand in expressed genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17015469", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 362, "text": "TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21214942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Transcription-coupled repair (TCR) is a subpathway of nucleotide excision repair (NER) that acts specifically on lesions in the transcribed strand of expressed genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "The blockage of transcription elongation by RNA polymerase II (pol II) at a DNA damage site on the transcribed strand triggers a transcription-coupled DNA repair (TCR), which rapidly removes DNA damage on the transcribed strand of the expressed gene and allows the resumption of transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15249207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "It has been previously shown that disruption of RAD26 in yeast strain W303-1B results in a strain that is deficient in transcription-coupled repair (TCR), the preferential repair of the transcribed strand of an expressed gene over the non-transcribed strand and the rest of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11452033", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 480, "text": "The proficient repair of the nontranscribed strand cannot be explained by the dedicated subpathway of transcription-coupled repair (TCR), which is targeted to the transcribed strand in expressed genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17015469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "A dedicated excision repair pathway, termed transcription-coupled repair (TCR), targets the removal of DNA lesions from transcribed strands of expressed genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16978026", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 616, "text": "NER can operate via two subpathways: global genome repair (GGR) and a specialized pathway coupled to active transcription (transcription-coupled repair, TCR) and directed to DNA lesions in the transcribed strand of active genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14599769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Transcription coupled repair (TCR) is a nucleotide excision repair (NER) pathway that is dedicated to repair in the transcribed strand of an active gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18817898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Transcription-coupled repair (TCR) is generally observed as more rapid or more efficient removal of certain types of DNA damage from the transcribed strands of expressed genes compared with the nontranscribed strands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15913669", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 496, "text": "In addition to the recognition and excision of DNA damage throughout the genome (GGR), there exists a mechanism, transcription-coupled nucleotide excision repair (TCR), for recognizing some types of DNA damage in the transcribed strand of genes in Escherichia coli, yeast and mammalian cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15186415", "endSection": "abstract" } ] }, { "body": "Abnormalities in which chromosomes were linked to the Moyamoya disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10754001", "http://www.ncbi.nlm.nih.gov/pubmed/23713105", "http://www.ncbi.nlm.nih.gov/pubmed/22426657", "http://www.ncbi.nlm.nih.gov/pubmed/15340753", "http://www.ncbi.nlm.nih.gov/pubmed/16164190", "http://www.ncbi.nlm.nih.gov/pubmed/23966756", "http://www.ncbi.nlm.nih.gov/pubmed/22436252", "http://www.ncbi.nlm.nih.gov/pubmed/21968521", "http://www.ncbi.nlm.nih.gov/pubmed/11037190", "http://www.ncbi.nlm.nih.gov/pubmed/17431895", "http://www.ncbi.nlm.nih.gov/pubmed/15675355", "http://www.ncbi.nlm.nih.gov/pubmed/20644152", "http://www.ncbi.nlm.nih.gov/pubmed/18576213", "http://www.ncbi.nlm.nih.gov/pubmed/24167642", "http://www.ncbi.nlm.nih.gov/pubmed/10757474", "http://www.ncbi.nlm.nih.gov/pubmed/9128751", "http://www.ncbi.nlm.nih.gov/pubmed/9973290", "http://www.ncbi.nlm.nih.gov/pubmed/19335127", "http://www.ncbi.nlm.nih.gov/pubmed/8898827", "http://www.ncbi.nlm.nih.gov/pubmed/21596366", "http://www.ncbi.nlm.nih.gov/pubmed/15675354", "http://www.ncbi.nlm.nih.gov/pubmed/20635402", "http://www.ncbi.nlm.nih.gov/pubmed/18463369", "http://www.ncbi.nlm.nih.gov/pubmed/23077562", "http://www.ncbi.nlm.nih.gov/pubmed/16475235", "http://www.ncbi.nlm.nih.gov/pubmed/19918425", "http://www.ncbi.nlm.nih.gov/pubmed/17138018", "http://www.ncbi.nlm.nih.gov/pubmed/18174554", "http://www.ncbi.nlm.nih.gov/pubmed/15362573", "http://www.ncbi.nlm.nih.gov/pubmed/8937199", "http://www.ncbi.nlm.nih.gov/pubmed/21631222", "http://www.ncbi.nlm.nih.gov/pubmed/16723886", "http://www.ncbi.nlm.nih.gov/pubmed/21048783" ], "ideal_answer": [ "chromosomes 3, 6, 8, 12, 15, 17, 21, X and Y were implicated in the Moyamoya disease." ], "exact_answer": [ [ "3" ], [ "6" ], [ "8" ], [ "12" ], [ "15" ], [ "17" ], [ "21" ], [ "X" ], [ "Y" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009072", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002875", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005694", "http://www.disease-ontology.org/api/metadata/DOID:13099", "http://www.disease-ontology.org/api/metadata/DOID:0080014" ], "type": "list", "id": "5312280ce3eabad02100000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Complex chromosome rearrangement of 6p25.3->p23 and 12q24.32->qter in a child with moyamoya.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23713105", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 534, "text": "Routine karyotype demonstrated extra chromosomal material on 6p. Single nucleotide polymorphism microarray revealed a previously unreported complex de novo genetic rearrangement involving subtelomeric segments on chromosomes 6p and 12q.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23713105", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 756, "text": "In terms of the genetics, recent literature suggests a low penetrance autosomal dominant or polygenic mode of transmission involving chromosomes 3, 6, 8, 12, and 17 for familial MMD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21631222", "endSection": "abstract" }, { "offsetInBeginSection": 1354, "offsetInEndSection": 1535, "text": "Furthermore, the current literature on familial MMD has pointed to a low penetrance autosomal dominant or polygenic mode of transmittance at loci on chromosomes 3, 6, 8, 12, and 17.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21631222", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 967, "text": "Here, we report on three unrelated families affected with an X-linked moyamoya syndrome characterized by the association of a moyamoya angiopathy, short stature, and a stereotyped facial dysmorphism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596366", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1259, "text": "We show that this syndromic moyamoya is caused by Xq28 deletions removing MTCP1/MTCP1NB and BRCC3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596366", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 575, "text": "A genome-wide association study of 785,720 single-nucleotide polymorphisms (SNPs) was performed, comparing 72 Japanese MMD patients with 45 Japanese controls and resulting in a strong association of chromosome 17q25-ter with MMD risk. This result was further confirmed by a locus-specific association study using 335 SNPs in the 17q25-ter region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21048783", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 587, "text": "Investigations included neuroimaging, cardiologic and ophthalmologic evaluation, hormonal testing, hemoglobin electrophoresis, chromosomal karyotyping, muscle biopsy for morphology, immunohistochemistry and enzyme assays, mtDNA mutation screening, and haplotype analysis of 2 loci previously linked to moyamoya, on chromosomes 10 (ACTA2) and 17.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644152", "endSection": "abstract" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1704, "text": "These data strongly suggest that this family is affected by a hereditary moyamoya multisystem disorder with X-linked recessive pattern of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644152", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 532, "text": "Her features were consistent with TS and chromosome analysis revealed mosaicism in which 17% of the cells showed a pseudoisodicentric Y chromosome: 45,X (25)/46,X psu idic (Y)(11.2) (5). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20635402", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1231, "text": "The small number of cases does not allow detailed analysis other than noting patient age (two older than 40 years), karyotype (two others associated with isochrome Xq), and associated cardiac risk factors (one with BAV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20635402", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 816, "text": " Studies have shown a possible genetic association of MMD linked to chromosome 17 in Japanese cases as well as in cases found in other demographics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19335127", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 436, "text": "The gene responsible for NF1 is located on the chromosome region 17q11.2 and for familial moyamoya disease on chromosome 17q25. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18576213", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Autosomal dominant moyamoya disease maps to chromosome 17q25.3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463369", "endSection": "title" }, { "offsetInBeginSection": 619, "offsetInEndSection": 1238, "text": "Under both classifications, significant evidence of linkage was only observed on chromosome 17q25.3, with maximum multipoint logarithm of odds (lod) scores of 6.57 (under the narrow classification) and 8.07 (under the broad classification) at D17S704. Haplotype analysis revealed segregation of a disease haplotype in all families but one, and informative crossovers enabled mapping of the MMD locus to a 3.5-Mb region between D17S1806 and the telomere of 17q, encompassing 94 annotated genes. CONCLUSIONS: Our data suggest that there is a major gene locus for autosomal dominant moyamoya disease on chromosome 17q25.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463369", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 915, "text": "However, the mitochondrial DNA and Y chromosomal genotype showed that affected members had the same sequence of the Mitochondrial 3 portion of D-loop with Japanese patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Smith-Magenis syndrome and Moyamoya disease in a patient with del(17)(p11.2p13.1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17431895", "endSection": "title" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1149, "text": "We have employed a combination of aCGH, FISH, and MLPA to characterize an approximately 6.3 Mb deletion spanning chromosome region 17p11.2-p13.1 in this patient, with the proximal breakpoint within the RAI1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17431895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Moyamoya syndrome in a child with trisomy 12p syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17138018", "endSection": "title" }, { "offsetInBeginSection": 669, "offsetInEndSection": 798, "text": "This report presents the first case of moyamoya syndrome with trisomy 12p with a familial pericentric inversion of chromosome 12.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17138018", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 399, "text": " She had been prenatally diagnosed with trisomy 12p with a familial pericentric inversion of chromosome 12 originating from her mother. She manifested developmental delay and some dysmorphic features of the face and limbs compatible with the clinical features of trisomy 12p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17138018", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 207, "text": "The genes encoding tissue inhibitor of metalloproteinase (TIMP) 4 and TIMP2 span chromosomes 3p24.2-p26 and 17q25, respectively, which are the locations of familial moyamoya disease (FMMD) genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16723886", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 708, "text": "We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of Down's syndrome with moyamoya syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16164190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "[Molecular screening for moyamoya disease by use of expressed sequence tag on chromosome 3p].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15675355", "endSection": "title" }, { "offsetInBeginSection": 307, "offsetInEndSection": 607, "text": " To identify the expressed sequence tags (ESTs) with monoallelic expressions on chromosome 3, we used mouse A9 hybrid cells having human chromosome 3. Two ESTs showed only maternal expression in mouse A9 hybrid cells, and four showed non-expression in the lymphocytes derived from moyamoya patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15675355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "A novel susceptibility locus for moyamoya disease on chromosome 8q23.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15362573", "endSection": "title" }, { "offsetInBeginSection": 335, "offsetInEndSection": 722, "text": "Previous linkage studies have indicated that susceptibility loci for the disease are located on chromosomes 3p, 6q, and 17q. In the present study, we searched for loci linked to the disease in 12 Japanese families using 428 microsatellite markers and found significant evidence for linkage to 8q23 [maximum LOD score (MLS) of 3.6] and suggestive evidence for linkage to 12p12 (MLS=2.3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15362573", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 503, "text": "Considering the function, we selected nine genes as candidates from a total of 65 genes identified in the 9-cM region of D17S785-D17S836 in chromosome 17q25, and performed sequence analysis on the DNA samples obtained from a pedigree of familial moyamoya disease, which showed a complete linkage to the region by a haplotype analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15340753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10754001", "endSection": "title" }, { "offsetInBeginSection": 189, "offsetInEndSection": 361, "text": "The characteristic lesions of moyamoya disease are occasionally seen in neurofibromatosis type 1, of which the causative gene (NF1) has been assigned to chromosome 17q11.2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10754001", "endSection": "abstract" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1340, "text": "CONCLUSIONS: A gene for familial moyamoya disease is located on chromosome 17q25.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10754001", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1192, "text": "Recent genetic studies suggest some responsible genetic foci in chromosomes 3, 6 and 17.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11037190", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 395, "text": "To further specify the genetic component of moyamoya disease, a linkage study of moyamoya disease using markers on chromosome 6, where the HLA gene is located, was performed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10757474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973290", "endSection": "title" }, { "offsetInBeginSection": 726, "offsetInEndSection": 799, "text": "A linkage was found between the disease and markers located at 3p24.2-26.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973290", "endSection": "abstract" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 1595, "text": "We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of moyamoya disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8898827", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 369, "text": "The diagnosis of PWS was confirmed genetically by the method of fluorescence in situ hybridization which showed the deletion of chromosome 15. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8937199", "endSection": "abstract" } ] }, { "body": "Which is the branch site consensus sequence in U12-dependent introns?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18824513" ], "ideal_answer": [ "The branch site consensus sequence in U12-dependent introns is UUCCUUAAC." ], "exact_answer": [ "UUCCUUAAC" ], "concepts": [ "http://www.uniprot.org/uniprot/PM14_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005689", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000348", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005693", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032921", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016384", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007438", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071017", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071015", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030626" ], "type": "factoid", "id": "5357a6d0f1005d6b58000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "Highly conserved sequences at the 5' splice site and branch site of U12-dependent introns are important determinants for splicing by U12-dependent spliceosomes. This study investigates the in vivo splicing phenotypes of mutations in the branch site consensus sequence of the U12-dependent intron F from a human NOL1 (P120) minigene. Intron F contains a fully consensus branch site sequence (UUCCUUAAC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824513", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 401, "text": "Intron F contains a fully consensus branch site sequence (UUCCUUAAC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824513", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 400, "text": "Intron F contains a fully consensus branch site sequence (UUCCUUAAC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824513", "endSection": "abstract" } ] }, { "body": "For what is Protein A from Staphylococcus aureus used in biochemistry?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22136061", "http://www.ncbi.nlm.nih.gov/pubmed/24184233", "http://www.ncbi.nlm.nih.gov/pubmed/22621885", "http://www.ncbi.nlm.nih.gov/pubmed/24033345", "http://www.ncbi.nlm.nih.gov/pubmed/12472184", "http://www.ncbi.nlm.nih.gov/pubmed/23776704", "http://www.ncbi.nlm.nih.gov/pubmed/24291195", "http://www.ncbi.nlm.nih.gov/pubmed/23770556" ], "ideal_answer": [ "Protein A from the bacterium Staphylococcus aureus (SpA) is used as an affinity ligand for purification of immunoglobulin G (IgG)." ], "concepts": [ "http://www.uniprot.org/uniprot/SRAP_STAAW", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013211", "http://www.uniprot.org/uniprot/SRAP_STAAU" ], "type": "summary", "id": "5523dc8c7b523f2123000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Staphylococcal protein A (SpA) binds Fc\u03b3 and VH3 clan Fab domains of human and animal immunoglobulin (Ig) with each of its five Ig binding domains (IgBDs),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Protein A from Staphylococcus aureus plays one key role as an immobilized affinity ligand for the purification of antibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24184233", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 215, "text": "The recombinant SpA is also widely used in biotechnology to purify polyclonal and monoclonal immunoglobulin G antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24033345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Staphylococcus aureus protein A (SpA) is the most popular affinity ligand for immunoglobulin G1 (IgG1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23776704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Staphylococcal Protein A (SPA), a cell wall protein of Staphylococcus aureus, is in high demand because of its ability to bind immunoglobulins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23770556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Protein A from the bacterium Staphylococcus aureus (SpA) has been widely used as an affinity ligand for purification of immunoglobulin G (IgG). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Affinity chromatography with protein A from Staphylococcus aureus (SpA) is the most widespread and accepted methodology for antibody capture during the downstream process of antibody manufacturing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22621885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Affinity chromatography using protein A from Staphylococcus aureus as the ligand has been widely used for the isolation of immunoglobulin G (IgG) from various species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12472184", "endSection": "abstract" } ] }, { "body": "What is the suggested therapy for Mycobacterium avium infection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19929882", "http://www.ncbi.nlm.nih.gov/pubmed/1832527", "http://www.ncbi.nlm.nih.gov/pubmed/9875582", "http://www.ncbi.nlm.nih.gov/pubmed/11073759", "http://www.ncbi.nlm.nih.gov/pubmed/1387133", "http://www.ncbi.nlm.nih.gov/pubmed/10714126", "http://www.ncbi.nlm.nih.gov/pubmed/16584300", "http://www.ncbi.nlm.nih.gov/pubmed/8733409" ], "ideal_answer": [ "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection. TLC G-65 in combination with rifapentine appears to be an attractive regimen for the treatment of infections caused by bacteria in the M. avium complex. Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. In vivo phage treatment may also be used in some cases.", "Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks", "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection" ], "type": "summary", "id": "5710ade4cf1c32585100002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1387133", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 880, "text": "TLC G-65 in combination with rifapentine appears to be an attractive regimen for the treatment of infections caused by bacteria in the M. avium complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1387133", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 621, "text": "Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9875582", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 493, "text": "TM4 is a lytic mycobacteriophage that kills both extracellular M. avium and M. tuberculosis. When delivered by M. smegmatis transiently infected with TM4, it kills both M. avium and M. tuberculosis within RAW 264.7 macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16584300", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 898, "text": "The patient was commenced on a 3-drug regimen with rifabutin, ethambutol and clarithromycin and has remained asymptomatic now for over 9 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10714126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11073759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1832527", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Evolution was favorable with multiple-drug therapy including rifampicin, ethambutol, and clarithromycin, along with a slight reduction in immunosuppression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19929882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The turning point in antimicrobial therapy of Mycobacterium avium infections came with the development of two new macrolides, clarithromycin and azithromycin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8733409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Clarithromycin against Mycobacterium avium complex infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8733409", "endSection": "title" } ] }, { "body": "What is the treatment of acute pericarditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18924029", "http://www.ncbi.nlm.nih.gov/pubmed/10560235", "http://www.ncbi.nlm.nih.gov/pubmed/12405580", "http://www.ncbi.nlm.nih.gov/pubmed/17415329", "http://www.ncbi.nlm.nih.gov/pubmed/12379412", "http://www.ncbi.nlm.nih.gov/pubmed/6966005", "http://www.ncbi.nlm.nih.gov/pubmed/7375968", "http://www.ncbi.nlm.nih.gov/pubmed/6727432", "http://www.ncbi.nlm.nih.gov/pubmed/20074469", "http://www.ncbi.nlm.nih.gov/pubmed/10920507", "http://www.ncbi.nlm.nih.gov/pubmed/17180574", "http://www.ncbi.nlm.nih.gov/pubmed/6726718", "http://www.ncbi.nlm.nih.gov/pubmed/308705" ], "ideal_answer": [ "A multidisciplinary approach is frequently necessary to treat acute pericarditis; the most frequent treatments are: antiinflammatory steroid and non-steroid drugs, antibiotic therapy, pericardial drainage and, less frequently ,intrapericardial irrigation of fibrinolytics; antituberculous chemotherapy in presence of Tuberculous Agent" ], "type": "summary", "id": "517a8ce98ed59a060a000045", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Recurrences develop in up to 20-50% of patients with acute pericarditis. Although different causes of recurrent pericarditis have been identified, the etiology remains obscure in most cases which are therefore labelled as idiopathic.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074469", "endSection": "sections.0" }, { "offsetInBeginSection": 1955, "offsetInEndSection": 2124, "text": "A poor response to colchicine treatment and/or a steroid-dependence may be the clue to investigate TNFRSF1A mutations in patients with idiopathic recurrent pericarditis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074469", "endSection": "sections.0" }, { "offsetInBeginSection": 338, "offsetInEndSection": 378, "text": "intravenous infusion of inotropic agents", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18924029", "endSection": "sections.0" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1343, "text": "medical treatment may be changed in these patients with a slower tapering of the dosage of steroidal and non-steroidal antiinflammatory drugs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17180574", "endSection": "sections.0" }, { "offsetInBeginSection": 462, "offsetInEndSection": 766, "text": "The incidence of purulent pericarditis has decreased considerably since the antibiotic era. It is typically an acute and potentially lethal disease, necessitating rapid diagnosis and adequate therapy to improve prognosis. Standard treatment combines appropriate antibiotic therapy with surgical drainage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12405580", "endSection": "sections.0" }, { "offsetInBeginSection": 478, "offsetInEndSection": 703, "text": "We report successful treatment of a non-resolving fibrino-purulent pericardial effusion by combined intrapericardial irrigation of fibrinolytics and systemic corticosteroids administration as an alternative to pericardectomy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12379412", "endSection": "sections.0" }, { "offsetInBeginSection": 1617, "offsetInEndSection": 1747, "text": "Prednisolone (20-30 mg/d) was used in addition to antituberculous chemotherapy in 11 of the 17 patients with effusive pericarditis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10560235", "endSection": "sections.0" }, { "offsetInBeginSection": 803, "offsetInEndSection": 1064, "text": "antibiotic therapy has been initiated. Use of appropriate parenterally administered antibiotics, in combination with early surgical pericardial drainage or partial pericardiectomy, should minimize morbidity and mortality and prevent acute constrictive sequelae.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6727432", "endSection": "sections.0" } ] }, { "body": "What is the genetic basis of tuberous sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24105488", "http://www.ncbi.nlm.nih.gov/pubmed/15579029", "http://www.ncbi.nlm.nih.gov/pubmed/10823953", "http://www.ncbi.nlm.nih.gov/pubmed/20073603", "http://www.ncbi.nlm.nih.gov/pubmed/15565817", "http://www.ncbi.nlm.nih.gov/pubmed/11520734", "http://www.ncbi.nlm.nih.gov/pubmed/9743993", "http://www.ncbi.nlm.nih.gov/pubmed/7546221", "http://www.ncbi.nlm.nih.gov/pubmed/15563017" ], "ideal_answer": [ "The genetic basis of tuberous sclerosis has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2. The functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, have remained ill defined until recently. Genetic, biochemical, and biologic analyses have highlighted their role as negative regulators of the mTOR signaling pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival. Emerging evidence also suggests that the TSC 1/2 complex may play a role in modulating the activity of beta-catenin and TGFbeta. These findings provide novel functional links between the TSC genes and other tumor suppressors.", "The genetic basis of this disease has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2.", "We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic TSC2 mutations in five of seven angiomyolipomas from sporadic LAM patients. Our data demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of TSC2 in the pathogenesis of this disease. The study of hereditary tumor syndromes has laid a solid foundation toward understanding the genetic basis of cancer." ], "exact_answer": [ "TSC1 and TSC2 genes" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402" ], "type": "factoid", "id": "56ed14d92ac5ed145900000a", "snippets": [ { "offsetInBeginSection": 620, "offsetInEndSection": 731, "text": "The genetic basis of this disease has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565817", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 984, "text": "The functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, have remained ill defined until recently", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565817", "endSection": "abstract" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1535, "text": "Genetic, biochemical, and biologic analyses have highlighted their role as negative regulators of the mTOR signaling pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival. Emerging evidence also suggests that the TSC 1/2 complex may play a role in modulating the activity of beta-catenin and TGFbeta. These findings provide novel functional links between the TSC genes and other tumor suppressors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565817", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 326, "text": "Ten years ago, a mutation in the TSC2 gene was identified in the Eker rat at Fox Chase Cancer Center by Yeung and Knudson, and in Tokyo by Kobayashi and Hino.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15579029", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 1052, "text": "Here, we will review the clinical association of RCC in TSC, consider the factors that have led to its under-emphasis within the RCC field, address the cellular and biochemical mechanisms that may contribute to RCC in cells with TSC1 or TSC2 mutations, and finally discuss the ways in which the TSC signaling pathways may be linked to sporadic RCC in the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15579029", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 231, "text": "Either of two genes, TSC1 or TSC2, can be mutated, resulting in the tuberous sclerosis complex phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15563017", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 409, "text": "The protein products of the tuberous sclerosis complex genes, hamartin (TSC1) and tuberin (TSC2), have been discovered to play important roles in several cell-signaling pathways", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15563017", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 520, "text": "Knowledge regarding the function of the tuberin-hamartin complex has led to therapeutic intervention trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15563017", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1579, "text": "TSC2 mutations were identified in all cyst-positive patients who were tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with nodular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11520734", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 666, "text": "We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10823953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10823953", "endSection": "title" }, { "offsetInBeginSection": 182, "offsetInEndSection": 306, "text": "The disease can be caused by mutations in either of two genes, TSC2, identified in 1993, and TSC1, only recently identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9743993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis (Tsc2)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7546221", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "We have recently identified on rat chromosome 10q a germline mutation in the tuberous sclerosis gene (Tsc2), the gene predisposing to renal carcinoma (RC) in the Eker rat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7546221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Tuberous sclerosis complex is a genetic disorder caused by mutations in either the TSC1 or TSC2 gene that can result in the growth of hamartomas in multiple organ systems", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105488", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 679, "text": "Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20073603", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 670, "text": "In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20073603", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 608, "text": "In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20073603", "endSection": "abstract" } ] }, { "body": "What is the molecular function of the Chd1 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "http://www.ncbi.nlm.nih.gov/pubmed/17098252", "http://www.ncbi.nlm.nih.gov/pubmed/21177652", "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "http://www.ncbi.nlm.nih.gov/pubmed/15647753", "http://www.ncbi.nlm.nih.gov/pubmed/23319591", "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "http://www.ncbi.nlm.nih.gov/pubmed/19948887" ], "ideal_answer": [ "The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. One of the two chromodomains of Chd1 specifically interacts with the methylated lysine 4 mark on histone H3 that is associated with transcriptional activity. Human CHD1 is an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4." ], "exact_answer": [ "Chd1 is an ATP-dependent DNA helicase" ], "concepts": [ "http://www.uniprot.org/uniprot/CHD1_MOUSE", "http://www.uniprot.org/uniprot/CHD1_DROME" ], "type": "factoid", "id": "57092332cf1c325851000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 728, "text": "The presence of these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means of efficiently harnessing the action of the Snf2-related ATPase domain for the purpose of nucleosome spacing and provide an explanation for partial redundancy between these proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 827, "text": "Here we identify the chromatin remodelling protein Chd1 (chromo-ATPase/helicase-DNA binding domain 1) as a component of SAGA and SLIK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15647753", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1012, "text": "one of the two chromodomains of Chd1 specifically interacts with the methylated lysine 4 mark on histone H3 that is associated with transcriptional activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15647753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "title" }, { "offsetInBeginSection": 196, "offsetInEndSection": 375, "text": "In the current study, we identify human CHD1, an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 692, "text": "human CHD1 binds to methylated H3K4 in a manner that requires both of its tandem chromodomains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1034, "text": "Our findings indicate that yeast and human CHD1 have diverged in their ability to discriminate covalently modified histones and link histone modification-recognition and non-covalent chromatin remodeling activities within a single human protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 397, "text": "We find that the yeast Isw1a, Isw2, and Chd1 enzymes preferentially move nucleosomes toward more central locations on short DNA fragments whereas Isw1b does not. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Analysis of nucleosome repositioning by yeast ISWI and Chd1 chromatin remodeling complexes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "endSection": "title" }, { "offsetInBeginSection": 555, "offsetInEndSection": 719, "text": "However, a key difference is that the Isw1a, Isw2, and Chd1 enzymes are unable to move nucleosomes to positions closer than 15 bp from a DNA end, whereas Isw1b can.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The ISWI and CHD1 chromatin remodelling activities influence ADH2 expression and chromatin organization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "title" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1002, "text": "Here we show that the absence of the Isw1 and Chd1 ATP-dependent chromatin remodelling activities delays the maximal expression of ADH2 without impairing the chromatin remodelling that occurs upon activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1701, "text": "Thus, the ISWI and Chd1 remodelling factors are not only involved in transcription-related chromatin remodelling, but also are required to maintain a specific chromatin configuration across the yeast genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1492, "text": "the lack of Chd1 combined with the absence of Isw1 and Isw2 impairs nucleosome spacing along the ADH2 gene, and genome-wide in S. cerevisiae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 991, "text": "Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6-9 proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177652", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1333, "text": "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 574, "text": "CHD1 is known to bind H3K4me3 in mammalian cells, and Neurospora CHD1 is required for proper regulation of the frequency (frq) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23319591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177652", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1358, "text": "Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in transcription.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948887", "endSection": "title" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1184, "text": "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177652", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1359, "text": "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": " Chromodomain from heterochromatin protein 1 and polycomb protein is known to be a lysine-methylated histone H3 tail-binding module. Chromo-helicase/ATPase DNA-binding protein 1 (CHD1) is an ATP-dependent chromatin remodeling factor, containing two tandem chromodomains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17098252", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1185, "text": "Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1185, "text": "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the FEC-75 regimen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8808724", "http://www.ncbi.nlm.nih.gov/pubmed/12525522", "http://www.ncbi.nlm.nih.gov/pubmed/16315865", "http://www.ncbi.nlm.nih.gov/pubmed/16282727", "http://www.ncbi.nlm.nih.gov/pubmed/1988577", "http://www.ncbi.nlm.nih.gov/pubmed/10885599", "http://www.ncbi.nlm.nih.gov/pubmed/22902450", "http://www.ncbi.nlm.nih.gov/pubmed/11875727", "http://www.ncbi.nlm.nih.gov/pubmed/18189160", "http://www.ncbi.nlm.nih.gov/pubmed/17647266", "http://www.ncbi.nlm.nih.gov/pubmed/22772380", "http://www.ncbi.nlm.nih.gov/pubmed/7693420", "http://www.ncbi.nlm.nih.gov/pubmed/24239210", "http://www.ncbi.nlm.nih.gov/pubmed/17054108", "http://www.ncbi.nlm.nih.gov/pubmed/10963640", "http://www.ncbi.nlm.nih.gov/pubmed/18344024" ], "ideal_answer": [ "Fluorouracil, epirubicin, and cyclophosphamide are included in the FEC-75 regimen. This chemotherapy regiment is used for breast cancer treatment." ], "exact_answer": [ [ "fluorouracil" ], [ "epirubicin" ], [ "cyclophosphamide" ] ], "type": "list", "id": "54df69af1388e8454a000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24239210", "endSection": "title" }, { "offsetInBeginSection": 697, "offsetInEndSection": 1272, "text": "Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24239210", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 255, "text": "In May 2008, the patient underwent preoperative chemotherapy consisting of 4 courses of FEC 75(fluororracil, epirubicin, and cyclophosphamide).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22902450", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 1098, "text": "Stage II-IIIC HER2-positive breast cancer patients, including inflammatory disease, were treated with weekly-trastuzumab for 24 weeks administered concurrently with all primary chemotherapy containing paclitaxel (80 mg/m(2)) for 12 weeks and 4 cycles of FEC-75 (fluorouracil 500 mg/m(2), epirubicine 75 mg/m(2), and cyclophosphamide 500 mg/m(2)) followed by surgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22772380", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 610, "text": "Further improvements can be achieved with dose-dense regimens, but densification of fluorouracil/epirubicin/cyclophosphamide (FEC) has proved difficult, with FEC(60) providing little benefit over standard chemotherapy and FEC(100) associated with toxicity. We investigated the feasibility of two intermediate dose-dense FEC regimens. Patients were randomised to six cycles of FEC(75) or FEC(90), with all three drugs given on day 1 of each 14-day cycle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18189160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "BACKGROUND: A previously published prospective randomized phase 3 trial showed that administration of 24 weeks of primary systemic chemotherapy (PST) with paclitaxel and FEC(75) (fluorouracil, epirubicin, cyclophosphamide) concurrently with trastuzumab in patients with HER2-positive primary breast cancer resulted in a 60% pathologic complete response rate (PCR) with no associated severe cardiac toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17647266", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 796, "text": "Maintenance chemotherapy was FEC 75 (fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) on Day 1 every 21 days for 4 cycles). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17054108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1988577", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 1105, "text": "Patients were randomised to 1 of 3 treatment groups: Group A (n = 207) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 6 cycles; Group B (n = 193) received FEC 50 every 21 days for 3 cycles; Group C (n = 195) received FEC 75 (fluorouracil 500 mg/m2, epirubicin 75 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 3 cycles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7693420", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 852, "text": "Sixty chemotherapy-naive breast cancer patients of 30 to 71 years in age, P.S. = 0-1, receiving 5-fluorouracil-epirubicin-cyclophosphamide (FEC 75) q 21 days or cyclophosphamide-methotrexate-5-fluorouracil (CMF) or 120 mg/m2 epirubicin or high dose mitomycin-methotrexate-mitoxantrone (MMM) q 14 days (+ G-CSF) or 100 mg/m2 epirubicin (+ G-CSF) were randomized to receive, 15 min before chemotherapy, 8 mg i.v. bolus of ondansetron or 3 mg i.v. granisetron or 5 mg i.v. tropisetron and no further antiemetic therapy in the following days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8808724", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 670, "text": "PATIENTS AND METHODS: Four hundred seventeen anthracycline-naive MBC patients were randomized to receive one of the following regimens: arm A: 11 cycles of fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 75) every 21 days; arm B: four cycles of FEC 100 (same regimen but with epirubicin 100 mg/m(2)) then eight cycles of FEC 50 (epirubicin 50 mg/m(2)); and arm C: four cycles of FEC 100 then restart the same regimen at disease progression in case of prior response or stabilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10963640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere 100 x mg x m(-2) docetaxel and FEC 75 cyclophosphamide 500 mg x m(-2), fluorouracil 500 x mg x m(-2) and epirubicin 75 mg x m(-2), in alternating and sequential schedules for the first-line treatment of metastatic breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11875727", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 609, "text": "PATIENTS AND METHODS: Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525522", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 471, "text": "We studied the feasibility of FEC (75) (fluorouracil: 500 mg/m(2), epirubicin: 75 mg/m(2), and cyclophosphamide:500 mg/m(2), q 3 w, 6 cycles) as adjuvant chemotherapy for 59 primary breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16282727", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 578, "text": "Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525522", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 640, "text": "Four hundred seventeen anthracycline-naive MBC patients were randomized to receive one of the following regimens: arm A: 11 cycles of fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 75) every 21 days; arm B: four cycles of FEC 100 (same regimen but with epirubicin 100 mg/m(2)) then eight cycles of FEC 50 (epirubicin 50 mg/m(2)); and arm C: four cycles of FEC 100 then restart the same regimen at disease progression in case of prior response or stabilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10963640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1988577", "endSection": "abstract" } ] }, { "body": "Between which probes does the recurrent translocation breakpoint on chromosome 22 of neuroepithelioma lie?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2303258" ], "ideal_answer": [ "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids", "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids. ", "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids.", "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids " ], "exact_answer": [ [ "D22S1" ], [ "D22S15" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056905", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014178", "http://www.disease-ontology.org/api/metadata/DOID:4388", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015342", "http://www.disease-ontology.org/api/metadata/DOID:4389" ], "type": "list", "id": "5536554abc4f83e828000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2303258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2303258", "endSection": "abstract" } ] }, { "body": "Does administration of triiodothyronine improve outcome following coronary artery bypass grafting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18290900", "http://www.ncbi.nlm.nih.gov/pubmed/16820580", "http://www.ncbi.nlm.nih.gov/pubmed/19303793", "http://www.ncbi.nlm.nih.gov/pubmed/8633935", "http://www.ncbi.nlm.nih.gov/pubmed/19609889", "http://www.ncbi.nlm.nih.gov/pubmed/7995828", "http://www.ncbi.nlm.nih.gov/pubmed/8389710", "http://www.ncbi.nlm.nih.gov/pubmed/10343261", "http://www.ncbi.nlm.nih.gov/pubmed/7477166", "http://www.ncbi.nlm.nih.gov/pubmed/23958074", "http://www.ncbi.nlm.nih.gov/pubmed/12213743", "http://www.ncbi.nlm.nih.gov/pubmed/8594265" ], "ideal_answer": [ "Perioperative administration of synthetic thyroid hormone therapy have positive hemodynamic effects (consisting of increases cardiac output, lowered systemic vascular resistance) determining improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, in the absence of relevant effects on outcome ad exception of lower incidence of atrial fibrillation." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047549", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020249", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001026", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.biosemantics.org/jochem#4275387", "http://www.disease-ontology.org/api/metadata/DOID:3393" ], "type": "yesno", "id": "532673c4d6d3ac6a34000009", "snippets": [ { "offsetInBeginSection": 889, "offsetInEndSection": 1204, "text": "Serum T3 concentrations were significantly higher with fewer patients having T3 concentrations below the normal range in the T3 group than the placebo group throughout the postoperative period. Hemodynamic variables, postoperative inotrope requirement, and outcome variables showed no differences between the groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23958074", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 835, "text": "We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18290900", "endSection": "abstract" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1588, "text": "Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16820580", "endSection": "abstract" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1222, "text": "Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12213743", "endSection": "abstract" }, { "offsetInBeginSection": 1614, "offsetInEndSection": 2031, "text": "Parenteral triiodothyronine given after crossclamp removal during elective coronary artery bypass grafting significantly improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, and decreased the incidence of myocardial ischemia. The incidence of atrial fibrillation was slightly decreased, and the need for postoperative pacemaker support was reduced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10343261", "endSection": "abstract" }, { "offsetInBeginSection": 1370, "offsetInEndSection": 1486, "text": "Perioperative T3 administration decreased the incidence and need for treatment of postoperative atrial fibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8633935", "endSection": "abstract" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1625, "text": " Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8594265", "endSection": "abstract" }, { "offsetInBeginSection": 1978, "offsetInEndSection": 2225, "text": "Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7477166", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1344, "text": "No significant differences were noted in the pre and post CPB hemodynamics between the two groups for the most part of the study except that heart rate was increased in T3 group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7995828", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1366, "text": "The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8389710", "endSection": "abstract" } ] }, { "body": "Which are the most widely used computational methods for the identification of CRMs (cis-regulatory modules)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22422841", "http://www.ncbi.nlm.nih.gov/pubmed/25268582", "http://www.ncbi.nlm.nih.gov/pubmed/15883375", "http://www.ncbi.nlm.nih.gov/pubmed/18606616", "http://www.ncbi.nlm.nih.gov/pubmed/20671200", "http://www.ncbi.nlm.nih.gov/pubmed/19478006", "http://www.ncbi.nlm.nih.gov/pubmed/21152003" ], "ideal_answer": [ "Computational methods attempting to identify instances of cis-regulatory modules (CRMs) in the genome face a challenging problem of searching for potentially interacting transcription factor binding sites while knowledge of the specific interactions involved remains limited. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. CisMiner allows to perform a blind search of CRMs without any prior information about target CRMs nor limitation in the number of motifs.", "The optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. A statistical model to describe the underlying cluster structure as well as individual motif conservation has also been proposed, accompanied with a Monte Carlo motif screening strategy for predicting novel regulatory modules in upstream sequences of coregulated genes." ], "exact_answer": [ [ "motif conservation" ], [ "fuzzy itemset mining" ], [ "combinatorial methods" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019295" ], "type": "list", "id": "56f3f0f02ac5ed1459000017", "snippets": [ { "offsetInBeginSection": 282, "offsetInEndSection": 663, "text": "Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). However, these tools present at least one of the following limitations: 1) scope limited to promoter or conserved regions of the genome; 2) do not allow to identify combinations involving more than two motifs; 3) require prior information about target motifs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268582", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 1219, "text": "In this work we present CisMiner, a novel methodology to detect putative CRMs by means of a fuzzy itemset mining approach able to operate at genome-wide scale. CisMiner allows to perform a blind search of CRMs without any prior information about target CRMs nor limitation in the number of motifs. CisMiner tackles the combinatorial complexity of genome-wide cis-regulatory module extraction using a natural representation of motif combinations as itemsets and applying the Top-Down Fuzzy Frequent- Pattern Tree algorithm to identify significant itemsets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268582", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 912, "text": "To be able to handle the large datasets, the query-based setting and other specificities proper to CRM detection on ChIP-Seq based data, we developed a novel powerful CRM detection method 'CPModule'", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22422841", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1379, "text": "the optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21152003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "CisMiner: genome-wide in-silico cis-regulatory module prediction by fuzzy itemset mining", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268582", "endSection": "title" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1306, "text": "Additionally, we make a number of new predictions on combinatorial regulation of these five key TFs with other TFs documented in TRANSFAC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22422841", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 597, "text": "Due to degeneracy of nucleotide content among binding site instances or motifs, and intricate 'grammatical organization' of motifs within cis-regulatory modules (CRMs), extant pattern matching-based in silico motif search methods often suffer from impractically high false positive rates, especially in the context of analyzing large genomic datasets, and noisy position weight matrices which characterize binding sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19478006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Genome-wide identification of cis-regulatory motifs and modules underlying gene coregulation using statistics and phylogeny.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20671200", "endSection": "title" }, { "offsetInBeginSection": 430, "offsetInEndSection": 693, "text": "We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-occurring in multiple CRMs. It can identify 'orthologous' CRMs without multiple alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606616", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 619, "text": "These methods are problematic when binding sites are not well aligned in multiple alignments or when the number of input known motifs is large. We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-occurring in multiple CRMs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606616", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 619, "text": "We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-occurring in multiple CRMs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606616", "endSection": "abstract" } ] }, { "body": "Which enzyme does MLN4924 inhibit?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22874562", "http://www.ncbi.nlm.nih.gov/pubmed/19360080", "http://www.ncbi.nlm.nih.gov/pubmed/24672057", "http://www.ncbi.nlm.nih.gov/pubmed/20142034", "http://www.ncbi.nlm.nih.gov/pubmed/21873567", "http://www.ncbi.nlm.nih.gov/pubmed/21969368", "http://www.ncbi.nlm.nih.gov/pubmed/24213570", "http://www.ncbi.nlm.nih.gov/pubmed/22951983", "http://www.ncbi.nlm.nih.gov/pubmed/25615422", "http://www.ncbi.nlm.nih.gov/pubmed/24634471", "http://www.ncbi.nlm.nih.gov/pubmed/21914854", "http://www.ncbi.nlm.nih.gov/pubmed/24525735", "http://www.ncbi.nlm.nih.gov/pubmed/21677879", "http://www.ncbi.nlm.nih.gov/pubmed/21994410", "http://www.ncbi.nlm.nih.gov/pubmed/22439935", "http://www.ncbi.nlm.nih.gov/pubmed/22012946", "http://www.ncbi.nlm.nih.gov/pubmed/25388161", "http://www.ncbi.nlm.nih.gov/pubmed/22072567", "http://www.ncbi.nlm.nih.gov/pubmed/21417215", "http://www.ncbi.nlm.nih.gov/pubmed/22927439", "http://www.ncbi.nlm.nih.gov/pubmed/21159650", "http://www.ncbi.nlm.nih.gov/pubmed/20129059", "http://www.ncbi.nlm.nih.gov/pubmed/24155378", "http://www.ncbi.nlm.nih.gov/pubmed/22832224", "http://www.ncbi.nlm.nih.gov/pubmed/21463634", "http://www.ncbi.nlm.nih.gov/pubmed/20525923", "http://www.ncbi.nlm.nih.gov/pubmed/23624319", "http://www.ncbi.nlm.nih.gov/pubmed/22246439", "http://www.ncbi.nlm.nih.gov/pubmed/23527154", "http://www.ncbi.nlm.nih.gov/pubmed/23986575" ], "ideal_answer": [ "MLN4924 is an investigational small molecule inhibitor of NEDD8-activating enzyme (NAE)." ], "exact_answer": [ "NEDD8-activating enzyme" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ], "type": "factoid", "id": "56ed03862ac5ed1459000004", "snippets": [ { "offsetInBeginSection": 880, "offsetInEndSection": 1110, "text": "Finally, MLN4924, an investigational small molecule inhibitor of NEDD8-activating enzyme (NAE) that inhibits CRL, suppresses in vitro migration, proliferation and tube formation, as well as in vivo angiogenesis and tumorigenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24213570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "MLN4924, a small molecule inhibitor of NEDD8 activating enzyme (NAE), has been reported to elicit an anti-tumor effect on various malignancies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25615422", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 693, "text": "The more targeted impact of NEDD8-activating enzyme on protein degradation prompted us to study MLN4924, an investigational NEDD8-activating enzyme inhibitor, in preclinical multiple myeloma models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "A gatekeeper residue for NEDD8-activating enzyme inhibition by MLN4924.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22832224", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Treatment-emergent mutations in NAE\u03b2 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22439935", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Quantifiable analysis of cellular pathway inhibition of a Nedd8-activating enzyme inhibitor, MLN4924, using AlphaScreen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624319", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Cellular effects of a Nedd8-activating enzyme (NAE) inhibitor, MLN4924, using the AlphaScreen format were explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Quantitative proteomic analysis of cellular protein modulation upon inhibition of the NEDD8-activating enzyme by MLN4924.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21873567", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Inactivation of the Cullin (CUL)-RING E3 ligase by the NEDD8-activating enzyme inhibitor MLN4924 triggers protective autophagy in cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22874562", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The Nedd8-activating enzyme inhibitor MLN4924 thwarts microenvironment-driven NF-\u03baB activation and induces apoptosis in chronic lymphocytic leukemia B cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24634471", "endSection": "title" }, { "offsetInBeginSection": 618, "offsetInEndSection": 778, "text": "Inhibition of Nedd8-activating enzyme by MLN4924 prevents the conjugation of cullin proteins with NEDD8, resulting in inactivation of the entire family of CRLs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21873567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129059", "endSection": "title" }, { "offsetInBeginSection": 708, "offsetInEndSection": 908, "text": "To inhibit cellular neddylation, we used a cell line with tetracycline-inducible expression of a dominant-negative form of the Nedd8 E2 enzyme or treatment of cells with the Nedd8 E1 inhibitor MLN4924", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21463634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155378", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 411, "text": "MLN4924 is an investigational agent that inhibits the Nedd8-activating enzyme, thereby neutralizing Cullin-RING ubiquitin ligases and preventing degradation of their substrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24634471", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 614, "text": "We used MLN4924, a phase 2 oncology therapeutic, which targets and inhibits the NEDD8-activating enzyme pathway involved in the ubiquitin-proteasome system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21994410", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 794, "text": "Neddylation occurs through a multistep enzymatic process involving Nedd8 activating enzymes, and recent studies have shown that the pharmacological agent, MLN4924, can potently inhibit Nedd8 activating enzymes, thereby preventing neddylation of Cullin proteins and preventing the degradation of CRL target proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22927439", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 694, "text": "The stability of the NEDD8-MLN4924 adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by MLN4924. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The NEDD8-activating enzyme inhibitor, MLN4924, cooperates with TRAIL to augment apoptosis through facilitating c-FLIP degradation in head and neck cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21914854", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Initial testing of the investigational NEDD8-activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22012946", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20525923", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": " MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE). Herein, we report that MLN4924 inhibits Vpx/Vpr-induced SAMHD1 degradation by inhibiting the neddylation of E3 ubiquitin ligase and blocks macaque simian immunodeficiency virus (SIVmac) replication in myeloid cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155378", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 987, "text": "Neddylation can be prevented by MLN4924, a drug that inhibits the nedd8-activating enzyme. We report that MLN4924 inhibits the neddylation of CRL4, blocking Vpx-induced degradation of SAMHD1 and maintaining the restriction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23986575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": " MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates. The mechanism by which MLN4924 inhibits cancer cell proliferation has not been defined, although it is accompanied by DNA rereplication and attendant DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159650", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 355, "text": "MLN4924 inhibits NAE (NEDD8 Activating Enzyme),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22072567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": " MLN4924 is an investigational small-molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trials for the treatment of cancer. MLN4924 is a mechanism-based inhibitor, with enzyme inhibition occurring through the formation of a tight-binding NEDD8-MLN4924 adduct.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22439935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 464, "text": "Ubiquitin-activating enzyme (UAE or E1) activates ubiquitin via an adenylate intermediate and catalyzes its transfer to a ubiquitin-conjugating enzyme (E2). MLN4924 is an adenosine sulfamate analogue that was identified as a selective, mechanism-based inhibitor of NEDD8-activating enzyme (NAE), another E1 enzyme, by forming a NEDD8-MLN4924 adduct that tightly binds at the active site of NAE, a novel mechanism termed substrate-assisted inhibition (Brownell, J.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21969368", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 272, "text": "(2010) elucidate the mechanism of action of MLN4924, a NEDD8-activating enzyme inhibitor. MLN4924 requires the activity of the enzyme to generate a NEDD8-adenylate analog that potently and selectively shuts down this posttranslational modification system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": " Cellular effects of a Nedd8-activating enzyme (NAE) inhibitor, MLN4924, using the AlphaScreen format were explored. MLN4924 acts as a substrate-assisted inhibitor of NAE by forming a tight binding Nedd8-MLN4924 adduct.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE). Herein, we report that MLN4924 inhibits Vpx/Vpr-induced SAMHD1 degradation by inhibiting the neddylation of E3 ubiquitin ligase and blocks macaque simian immunodeficiency virus (SIVmac) replication in myeloid cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates. The mechanism by which MLN4924 inhibits cancer cell proliferation has not been defined, although it is accompanied by DNA rereplication and attendant DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "MLN4924 is an investigational small-molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trials for the treatment of cancer. MLN4924 is a mechanism-based inhibitor, with enzyme inhibition occurring through the formation of a tight-binding NEDD8-MLN4924 adduct.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22439935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Cellular effects of a Nedd8-activating enzyme (NAE) inhibitor, MLN4924, using the AlphaScreen format were explored. MLN4924 acts as a substrate-assisted inhibitor of NAE by forming a tight binding Nedd8-MLN4924 adduct.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624319", "endSection": "abstract" } ] }, { "body": "Which protein has been found to interact with phospholamban (PLN) and is also an anti-apoptotic protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "http://www.ncbi.nlm.nih.gov/pubmed/18971376", "http://www.ncbi.nlm.nih.gov/pubmed/18415121", "http://www.ncbi.nlm.nih.gov/pubmed/17241641", "http://www.ncbi.nlm.nih.gov/pubmed/24550830" ], "ideal_answer": [ "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function.The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca(2+) homeostasis and cell survival, with significant therapeutic potential.", "The HS-1 associated protein X-1 (HAX-1) is a mitochondrial protein with anti-apoptotic function and presents with numerous similarities to Bcl-2. and was identified as a phospholamban-binding partner. Using the yeast-two-hybrid system, HS-1 associated protein X-1 (HAX-1) was identified as a PLN-binding partner.", "The sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation. Recently, the antiapoptotic HS-1-associated protein X-1 (HAX-1) was identified as a binding partner of PLN, and this interaction was postulated to regulate cell apoptosis.Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function." ], "exact_answer": [ "The HS-1 associated protein X-1", "(HAX-1)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051017", "http://www.uniprot.org/uniprot/PPLA_RABIT", "http://www.uniprot.org/uniprot/PPLA_RAT", "http://www.uniprot.org/uniprot/PPLA_CHICK", "http://www.uniprot.org/uniprot/PPLA_MOUSE", "http://www.uniprot.org/uniprot/PPLA_BOVIN", "http://www.uniprot.org/uniprot/PPLA_CANFA", "http://www.uniprot.org/uniprot/PPLA_PIG" ], "type": "factoid", "id": "54f9cb34dd3fc62544000002", "snippets": [ { "offsetInBeginSection": 260, "offsetInEndSection": 479, "text": "To identify additional proteins that may interact with PLN, we used the yeast-two-hybrid system to screen an adult human cardiac cDNA library. HS-1 associated protein X-1 (HAX-1) was identified as a PLN-binding partner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241641", "endSection": "abstract" }, { "offsetInBeginSection": 1348, "offsetInEndSection": 1669, "text": "Analysis of the anti-apoptotic function of HAX-1 revealed that the presence of PLN enhanced the HAX-1 protective effects from hypoxia/reoxygenation-induced cell death. These findings suggest a possible link between the Ca(2+) handling by the sarcoplasmic reticulum and cell survival mediated by the PLN/HAX-1 interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241641", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 800, "text": "The sarco(endo)plasmic reticulum Ca(2+) transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca(2+) homeostasis and, therefore, cardiac function. Herein, we discuss the mechanisms through which SERCA2a and PLN control cardiomyocyte function in health and disease. Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18415121", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1123, "text": "The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca(2+) homeostasis and cell survival, with significant therapeutic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18415121", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 442, "text": "The sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation. Recently, the antiapoptotic HS-1-associated protein X-1 (HAX-1) was identified as a binding partner of PLN, and this interaction was postulated to regulate cell apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971376", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1038, "text": "On triple transfections with PLN, however, HAX-1 massively translocated to the ER membranes, where it codistributed with PLN and SERCA2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971376", "endSection": "abstract" }, { "offsetInBeginSection": 1343, "offsetInEndSection": 1473, "text": "These findings suggest that HAX-1 may promote cell survival through modulation of SERCA2 protein levels and thus ER Ca(2+) stores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241641", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 407, "text": "The HS-1 associated protein X-1 (HAX-1) is a ubiquitously expressed protein that protects cardiomyocytes from programmed cell death. Here we identify HAX-1 as a regulator of contractility and calcium cycling in the heart. HAX-1 overexpression reduced sarcoplasmic reticulum Ca-ATPase (SERCA2) pump activity in isolated cardiomyocytes and in vivo, leading to depressed myocyte calcium kinetics and mechanics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 723, "text": "The inhibitory effects of HAX-1 were abolished upon phosphorylation of phospholamban, which plays a fundamental role in controlling basal contractility and constitutes a key downstream effector of the beta-adrenergic signaling cascade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 978, "text": " Furthermore, the effects of PLN and its phosphorylation on cardiac function are subject to additional regulation by its interacting partners, the anti-apoptotic HAX-1 protein and Gm or the anchoring unit of protein phosphatase 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24550830", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 796, "text": " Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18415121", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 982, "text": "Furthermore, the effects of PLN and its phosphorylation on cardiac function are subject to additional regulation by its interacting partners, the anti-apoptotic HAX-1 protein and Gm or the anchoring unit of protein phosphatase 1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24550830", "endSection": "abstract" } ] }, { "body": "Is long QT syndrome a cause for sudden cardiac death in athletes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17853713", "http://www.ncbi.nlm.nih.gov/pubmed/22362900", "http://www.ncbi.nlm.nih.gov/pubmed/20675977", "http://www.ncbi.nlm.nih.gov/pubmed/22375212", "http://www.ncbi.nlm.nih.gov/pubmed/20089483", "http://www.ncbi.nlm.nih.gov/pubmed/17726868", "http://www.ncbi.nlm.nih.gov/pubmed/16672832", "http://www.ncbi.nlm.nih.gov/pubmed/12831662", "http://www.ncbi.nlm.nih.gov/pubmed/11475927", "http://www.ncbi.nlm.nih.gov/pubmed/24198575", "http://www.ncbi.nlm.nih.gov/pubmed/15074012", "http://www.ncbi.nlm.nih.gov/pubmed/19535269", "http://www.ncbi.nlm.nih.gov/pubmed/15184297", "http://www.ncbi.nlm.nih.gov/pubmed/21234187" ], "ideal_answer": [ "One of several causes of sudden cardiac death in athletes is long QT syndrome" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016757", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008133", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ], "type": "yesno", "id": "53009f6d2059c6d71c00007e", "snippets": [ { "offsetInBeginSection": 151, "offsetInEndSection": 573, "text": "A diversity of cardiovascular disorders including hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, aortic rupture due to Marfan syndrome, myocarditis, valvular disease and electrical disorders (Wolff-Parkinson-White syndrome, long QT syndrome, Brugada syndrome), as well as commotio cordis represent the common causes of SCD in young athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22375212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Sudden cardiac death is the leading cause of mortality among young athletes with an incidence of 1-2 per 100,000 athletes per annum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362900", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 691, "text": "The majority of cases are caused by an underlying structural cardiac abnormality, most commonly hypertrophic cardiomyopathy. More recently, the understanding of non-structural causes such as long QT syndrome and Brugada syndrome has grown and diagnostic criteria have been developed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362900", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 484, "text": "This review considers in particular the causes of death affecting athletes below 35 years of age. In this age group the largest proportion of deaths are caused by diseases with autosomal dominant inheritance such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT-syndrome, and Marfan's syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Knowledge of sudden cardiac death in young athletes is imperative for all physicians and allied health professionals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20675977", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 493, "text": "In this article, we review several etiologies of sudden cardiac death, including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, Wolff-Parkinson-White syndrome, long QT syndrome, Brugada syndrome, and commotio cordis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20675977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Sudden cardiac death (SCD) in young athletes is generally caused by inherited cardiac disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089483", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 471, "text": "The genetic abnormalities most associated with SCD are hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089483", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 789, "text": "The most common cause of sudden cardiac death in athletes is hypertrophic cardiomyopathy. Other reasons are congenital coronary artery anomalies, nivocarditis, dilatative cardiomyopathy, arrhythmogenic cardiomyopathy of the right ventricle, sarcoidosis, mitral valve prolapse, aortic valve stenosis, atherosclerosis, long QT syndrome, and blunt impact to the chest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17853713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The congenital long QT syndrome (LQTS) is caused by cardiac ion channel mutations, which predispose young individuals to sudden cardiac death often related to exercise. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16672832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "A group of relatively uncommon but important genetic cardiovascular diseases (GCVDs) are associated with increased risk for sudden cardiac death during exercise, including hypertrophic cardiomyopathy, long-QT syndrome, Marfan syndrome, and arrhythmogenic right ventricular cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15184297", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 383, "text": "Primary electrical disorders (such as the long QT syndrome) are rarely present in athletes but, so far, are a considerable reason for disqualification from sport activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12831662", "endSection": "abstract" } ] }, { "body": "What is the clinical value of MammaPrint?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "http://www.ncbi.nlm.nih.gov/pubmed/20110242", "http://www.ncbi.nlm.nih.gov/pubmed/20975745", "http://www.ncbi.nlm.nih.gov/pubmed/19125125", "http://www.ncbi.nlm.nih.gov/pubmed/21847392", "http://www.ncbi.nlm.nih.gov/pubmed/18159035", "http://www.ncbi.nlm.nih.gov/pubmed/19825882", "http://www.ncbi.nlm.nih.gov/pubmed/19214742" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7746488", "o": "Clinic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8316941", "o": "Clinical" } ], "ideal_answer": [ "MammaPrint has a prognostic value for distant metastasis and death, as well as predictive value for response to adjuvant chemotherapy in patients with breast cancer. However, the EGAPP Working Group found no evidence regarding the clinical utility of the MammaPrint." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013677", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003695", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008495", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019411", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015510" ], "type": "summary", "id": "51485b9ad24251bc0500002b", "snippets": [ { "offsetInBeginSection": 1118, "offsetInEndSection": 1280, "text": "In the intermediate-risk subgroup, the 70-gene signature could be useful to decide in elderly patients whether they may benefit from adjuvant chemotherapy or not.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "endSection": "sections.0" }, { "offsetInBeginSection": 209, "offsetInEndSection": 401, "text": "Adjuvant assessment tools for prognosis and prediction of treatment benefit, including Adjuvant! Online, the St Gallen Consensus, Oncotype DX(\u00ae) and MammaPrint(\u00ae), aid clinical decision making", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20975745", "endSection": "sections.0" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1368, "text": "The 70-gene MammaPrint prognosis profile accurately identified Japanese breast cancer patients at low risk of developing recurrences. In fact, 100% of the individuals in the low-risk category remained metastasis-free for the duration of the observation period.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110242", "endSection": "sections.0" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1094, "text": "he probability of distant metastasis-free survival at five years was 100% for the low-risk group and 94% for the high-risk group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110242", "endSection": "sections.0" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1350, "text": "The 70-gene prognosis signature can accurately select postmenopausal patients at low risk of breast cancer-related death within 5 years of diagnosis and can be of clinical use in selecting postmenopausal women for adjuvant chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19825882", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The 70-gene signature (MammaPrint) is a prognostic tool used to guide adjuvant treatment decisions", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214742", "endSection": "sections.0" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1036, "text": "A pCR is unlikely to be achieved in tumors that have a good prognosis-signature. Tumors with a poor prognosis-signature are more sensitive to chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214742", "endSection": "sections.0" }, { "offsetInBeginSection": 2090, "offsetInEndSection": 2349, "text": "The EWG found adequate evidence to characterize the association of MammaPrint with future metastases, but inadequate evidence to assess the added value to standard risk stratification, and could not determine the population to which the test would best apply.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125125", "endSection": "sections.0" }, { "offsetInBeginSection": 2458, "offsetInEndSection": 2665, "text": "he EWG found no evidence regarding the clinical utility of the MammaPrint and Quest H:I Ratio tests, and inadequate evidence regarding Oncotype DX. These technologies have potential for both benefit and harm", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125125", "endSection": "sections.0" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1323, "text": "MammaPrint, an oligonucleotide microassay performed on fresh-frozen tumor samples, analyzes the expression of 70 genes. Studies have found that MammaPrint allows young patients (<61 years) with early-stage breast cancer to be categorized as having a high or low risk of distant metastasis. High-risk patients may then be managed with more aggressive therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18159035", "endSection": "sections.0" } ] }, { "body": "Is protein M3/6 a dual specificity phosphatase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15888437", "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "http://www.ncbi.nlm.nih.gov/pubmed/8910287", "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "http://www.ncbi.nlm.nih.gov/pubmed/11948422", "http://www.ncbi.nlm.nih.gov/pubmed/12524447", "http://www.ncbi.nlm.nih.gov/pubmed/12598532", "http://www.ncbi.nlm.nih.gov/pubmed/10915787", "http://www.ncbi.nlm.nih.gov/pubmed/23159405" ], "ideal_answer": [ "M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs.", "Yes. Phosphatases play a particularly important role in this respect, by tightly controlling MAPK phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins.", "The protein M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK" ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016791", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054638", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054637", "http://www.uniprot.org/uniprot/DUS1_RAT", "http://www.uniprot.org/uniprot/DUS8_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008138", "http://www.uniprot.org/uniprot/DUS2_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004712", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054641", "http://www.uniprot.org/uniprot/DUS3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0017017", "http://www.uniprot.org/uniprot/DUS8_HUMAN" ], "type": "yesno", "id": "5512cce26a8cde6b7200000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Involvement of the dual-specificity phosphatase M3/6 in c-Jun N-terminal kinase inactivation following cerebral ischemia in the rat hippocampus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "endSection": "title" }, { "offsetInBeginSection": 324, "offsetInEndSection": 453, "text": "The results revealed upregulation of dual-specificity phosphatase M3/6 (DUSP8) activity at 4\u00a0h of reperfusion in rat hippocampi. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 323, "text": "This study examines the molecular mechanism underlying JNK dephosphorylation and inactivation evoked by dual-specificity phosphates following cerebral ischemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 677, "text": "Phosphatases play a particularly important role in this respect, by tightly controlling MAPK phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159405", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 448, "text": "Dual-specificity phosphatases (DUSPs) play a very important role in these events by modulating the extent of JNK phosphorylation and activation and thus regulating cellular responses to stress. M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 702, "text": "M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 555, "text": "Here we describe two new dual specificity phosphatases of the CL100/MKP-1 family that are selective for inactivating ERK or JNK/SAPK and p38 MAP kinases when expressed in COS-7 cells. M3/6 is the first phosphatase of this family to display highly specific inactivation of JNK/SAPK and p38 MAP kinases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8910287", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 319, "text": "We previously demonstrated that the dual specificity phosphatases (DSPs) MKP7 and M3/6 bind the scaffold JNK-interacting protein-1 (JIP-1) and inactivate the bound subset of JNK (1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15888437", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 52, "text": "the dual-specificity phosphatase M3/6", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "endSection": "title" }, { "offsetInBeginSection": 360, "offsetInEndSection": 402, "text": " dual-specificity phosphatase M3/6 (DUSP8)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 523, "text": "M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159405", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 56, "text": "the M3/6 dual-specificity phosphatase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "title" }, { "offsetInBeginSection": 345, "offsetInEndSection": 447, "text": "M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 693, "text": "M3/6 is a dual-specificity phosphatase selective for JNK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8910287", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Phosphorylation of the M3/6 dual-specificity phosphatase enhances the activation of JNK by arsenite.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "title" }, { "offsetInBeginSection": 581, "offsetInEndSection": 681, "text": "Indeed, expanded polyglutamine impaired the solubility of the dual-specificity JNK phosphatase M3/6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12598532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Regulation of dual-specificity phosphatases M3/6 and hVH5 by phorbol esters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10915787", "endSection": "title" }, { "offsetInBeginSection": 345, "offsetInEndSection": 448, "text": "M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 699, "text": "M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 446, "text": "M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 429, "text": "Here we describe how diverse cellular stresses affect differently the stability and activity of a JNK-inactivating dual-specificity threonine-tyrosine phosphatase M3/6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11948422", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 700, "text": "M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Regulation of dual-specificity phosphatases M3/6 and hVH5 by phorbol esters. Analysis of a delta-like domain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10915787", "endSection": "title" }, { "offsetInBeginSection": 324, "offsetInEndSection": 451, "text": "The results revealed upregulation of dual-specificity phosphatase M3/6 (DUSP8) activity at 4\u00a0h of reperfusion in rat hippocampi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 680, "text": "Indeed, expanded polyglutamine impaired the solubility of the dual-specificity JNK phosphatase M3/6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12598532", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 689, "text": "Here we report that JIP-1 also binds the dual-specificity phosphatases MKP7 and M3/6 via a region independent of its JNK binding domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12524447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Differential regulation of M3/6 (DUSP8) signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159405", "endSection": "title" } ] }, { "body": "Are there focused databases from which you can retrieve gene expression data on renal disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20616184", "http://www.ncbi.nlm.nih.gov/pubmed/23593176", "http://www.ncbi.nlm.nih.gov/pubmed/21143788", "http://www.ncbi.nlm.nih.gov/pubmed/19604367", "http://www.ncbi.nlm.nih.gov/pubmed/21044771", "http://www.ncbi.nlm.nih.gov/pubmed/21930502", "http://www.ncbi.nlm.nih.gov/pubmed/19703314", "http://www.ncbi.nlm.nih.gov/pubmed/17877839" ], "ideal_answer": [ "Biological databases are used to store and edit large amount of data, created from genomics data. In the most of the cases the data are stored according to their type but there are cases of focused databases that store database on a specific disease. In the case of renal disease there are plenty of databases, for example KUPKB a collection of omics datasets, Nephromine a renal genome-wide gene expression dataset based in transcriptomics, CDKD and Proteomics Database in Chronic Kidney Disease." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020869", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051436", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007674", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870" ], "type": "yesno", "id": "532c0946d6d3ac6a34000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Proteomics database in chronic kidney disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21044771", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616184", "endSection": "title" } ] }, { "body": "What systems have been developed for the numbering of antibody residues?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9367782", "http://www.ncbi.nlm.nih.gov/pubmed/22907343", "http://www.ncbi.nlm.nih.gov/pubmed/8227075", "http://www.ncbi.nlm.nih.gov/pubmed/22665257", "http://www.ncbi.nlm.nih.gov/pubmed/2687698", "http://www.ncbi.nlm.nih.gov/pubmed/18503082", "http://www.ncbi.nlm.nih.gov/pubmed/10592229", "http://www.ncbi.nlm.nih.gov/pubmed/19900967", "http://www.ncbi.nlm.nih.gov/pubmed/12182069", "http://www.ncbi.nlm.nih.gov/pubmed/16305737", "http://www.ncbi.nlm.nih.gov/pubmed/8918594", "http://www.ncbi.nlm.nih.gov/pubmed/23157214", "http://www.ncbi.nlm.nih.gov/pubmed/22390639" ], "ideal_answer": [ "The most prevalent antibody numbering systems are the Kabat system, the Chothia system as well as the IMGT numbering system." ], "concepts": [ "http://www.biosemantics.org/jochem#4000002", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007158", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003823", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007136", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906" ], "type": "summary", "id": "532ad23ad6d3ac6a34000011", "snippets": [ { "offsetInBeginSection": 217, "offsetInEndSection": 771, "text": "IMGT is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune system (RPI) of any species which belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF). IMGT consists of five databases, ten on-line tools and more than 8,000 HTML pages of Web resources. IMGT provides a common access to standardized data from genome, genetics, proteome and three-dimensional structures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16305737", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1121, "text": "amino acid positions according to the IMGT unique numbering (NUMEROTATION) that are used in IMGT/3Dstructure-DB cards, results of contact analysis and renumbered flat files.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19900967", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 691, "text": "Standardized sequence and structure analysis of antibody using IMGT(\u00ae) databases and tools allows one to bridge, for the first time, the gap between antibody sequences and three-dimensional (3D) structures. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts of classification (IMGT gene and allele nomenclature), description (IMGT standardized labels), and numerotation (IMGT unique numbering and IMGT Colliers de Perles). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22907343", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 152, "text": "Kabat Database was initially started in 1970 to determine the combining site of antibodies based on the available amino acid sequences at that time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10592229", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 855, "text": "comparative analysis of the main-chain conformation of the L1, L2, L3, H1 and H2 hypervariable regions in 17 immunoglobulin structures that have been accurately determined at high resolution is described. This involves 79 hypervariable regions in all. We also analysed a part of the H3 region in 12 of the 15 VH domains considered here. On the basis of the residues at key sites the 79 hypervariable regions can be assigned to one of 18 different canonical structures. We show that 71 of these hypervariable regions have a conformation that is very close to what can be defined as a \"standard\" conformation of each canonical structure. These standard conformations are described in detail. The other eight hypervariable regions have small deviations from the standard conformations that, in six cases, involve only the rotation of a single peptide group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9367782", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 316, "text": "the basis of comparative studies of known antibody structures and sequences it has been argued that there is a small repertoire of main-chain conformations for at least five of the six hypervariable regions of antibodies, and that the particular conformation adopted is determined by a few key conserved residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2687698", "endSection": "abstract" } ] }, { "body": "Are there any DNMT3 proteins present in plants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22058406", "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "http://www.ncbi.nlm.nih.gov/pubmed/15946751", "http://www.ncbi.nlm.nih.gov/pubmed/17660570", "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "http://www.ncbi.nlm.nih.gov/pubmed/21150311", "http://www.ncbi.nlm.nih.gov/pubmed/23021223", "http://www.ncbi.nlm.nih.gov/pubmed/21060858", "http://www.ncbi.nlm.nih.gov/pubmed/15282033", "http://www.ncbi.nlm.nih.gov/pubmed/9584105", "http://www.ncbi.nlm.nih.gov/pubmed/18488247", "http://www.ncbi.nlm.nih.gov/pubmed/12121623", "http://www.ncbi.nlm.nih.gov/pubmed/12151602", "http://www.ncbi.nlm.nih.gov/pubmed/10781108" ], "ideal_answer": [ "Yes. The plant DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2) is a homolog of the mammalian de novo methyltransferase DNMT3. DRM2 contains a novel arrangement of the motifs required for DNA methyltransferase catalytic activity." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/CMT3_ARATH", "http://www.uniprot.org/uniprot/CMT2_ARATH", "http://www.uniprot.org/uniprot/CMT1_ARATH" ], "type": "yesno", "id": "511a16f9df1ebcce7d000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "De novo DNA methylation in Arabidopsis thaliana is catalyzed by the methyltransferase DRM2, a homolog of the mammalian de novo methyltransferase DNMT3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150311", "endSection": "sections.0" }, { "offsetInBeginSection": 387, "offsetInEndSection": 851, "text": "Here we describe DNA methyltransferase genes from both Arabidopsis and maize that show a high level of sequence similarity to Dnmt3, suggesting that they encode plant de novo methyltransferases. Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity. The N termini of these methyltransferases contain a series of ubiquitin-associated (UBA) domains. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10781108", "endSection": "sections.0" }, { "offsetInBeginSection": 365, "offsetInEndSection": 519, "text": "BLASTX searches and phylogenetic analysis suggested that five cDNAs belonged to four classes (Dnmt1, Dnmt2, CMT and Dnmt3) of DNA methyltransferase genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15946751", "endSection": "sections.0" } ] }, { "body": "What is the number of protein coding genes in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18040051", "http://www.ncbi.nlm.nih.gov/pubmed/15034132", "http://www.ncbi.nlm.nih.gov/pubmed/20175080", "http://www.ncbi.nlm.nih.gov/pubmed/22955987" ], "ideal_answer": [ "The number of protein coding genes in the human genome is currently estimated between 20,000 and 25,000" ], "exact_answer": [ "Between 20,000 and 25,000" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016366", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "factoid", "id": "535d3c069a4572de6f000006", "snippets": [ { "offsetInBeginSection": 277, "offsetInEndSection": 556, "text": "Here, seven membrane protein topology prediction methods based on different underlying algorithms, such as hidden Markov models, neural networks and support vector machines, have been used for analysis of the protein sequences from the 21,416 annotated genes in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20175080", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 523, "text": "he GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955987", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 220, "text": "Current catalogs list a total of approximately 24,500 putative protein-coding genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18040051", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 442, "text": "Clustering of these sequences using cross-species relationships suggests that millions of expressed sequences may correspond to only approximately 20,000 distinct protein-coding transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15034132", "endSection": "abstract" } ] }, { "body": "Has vitamin D has been shown to reduce incidence of falls in older people in clinical trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20796001", "http://www.ncbi.nlm.nih.gov/pubmed/21795448", "http://www.ncbi.nlm.nih.gov/pubmed/20136906", "http://www.ncbi.nlm.nih.gov/pubmed/22972103", "http://www.ncbi.nlm.nih.gov/pubmed/23922354", "http://www.ncbi.nlm.nih.gov/pubmed/18979152", "http://www.ncbi.nlm.nih.gov/pubmed/20230348", "http://www.ncbi.nlm.nih.gov/pubmed/23728680" ], "ideal_answer": [ "The rate of falls and the number of fallers was significantly reduced in two studies evaluating the effect of medication on preventing falls; one study (85 participants) compared vitamin D versus placebo in institutionalised women after stroke with low vitamin D levels, and the other study (79 participants) evaluated alendronate versus alphacalcidol in hospitalised people after stroke.\nTwo studies testing vitamin D versus placebo and alendronate versus alphacalcidol found a significant reduction in falls and the number of people falling.\nOverall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment.\nWe found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96)" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014807", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004872", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002762", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014808" ], "type": "yesno", "id": "530cf57efe2466f70c000006", "snippets": [ { "offsetInBeginSection": 503, "offsetInEndSection": 682, "text": "However, apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly, causality remains yet unproven in randomized controlled trials (RCTs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23922354", "endSection": "abstract" }, { "offsetInBeginSection": 2457, "offsetInEndSection": 2845, "text": "The rate of falls and the number of fallers was significantly reduced in two studies evaluating the effect of medication on preventing falls; one study (85 participants) compared vitamin D versus placebo in institutionalised women after stroke with low vitamin D levels, and the other study (79 participants) evaluated alendronate versus alphacalcidol in hospitalised people after stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728680", "endSection": "abstract" }, { "offsetInBeginSection": 3420, "offsetInEndSection": 3573, "text": "Two studies testing vitamin D versus placebo and alendronate versus alphacalcidol found a significant reduction in falls and the number of people falling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728680", "endSection": "abstract" }, { "offsetInBeginSection": 6029, "offsetInEndSection": 6177, "text": ".Overall, vitamin D supplementation does not appear to reduce falls but may be effective in people who have lower vitamin D levels before treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728680", "endSection": "abstract" }, { "offsetInBeginSection": 2538, "offsetInEndSection": 2803, "text": "Overall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22972103", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 102, "text": "Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795448", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 1041, "text": "We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795448", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1193, "text": "This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795448", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1356, "text": "Vitamin D combined with calcium reduces the risk of falls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795448", "endSection": "abstract" }, { "offsetInBeginSection": 1455, "offsetInEndSection": 1531, "text": "The majority of the evidence is derived from trials enrolling elderly women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20796001", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1081, "text": "Despite significant increases in the provision of hip protectors and use of vitamin D supplementation in both intervention and control facilities, there was no difference in the number of falls or falls injuries between the intervention and control groups, nor a reduction in falls overall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20230348", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 379, "text": "Beyond fall and fracture prevention, vitamin D may also reduce overall morbidity by multiple mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20136906", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1341, "text": "There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18979152", "endSection": "abstract" } ] }, { "body": "What is the indication for prophylactic use of antibiotics in COPD?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20477251", "http://www.ncbi.nlm.nih.gov/pubmed/22108462", "http://www.ncbi.nlm.nih.gov/pubmed/11498704" ], "ideal_answer": [ "In a subset of patients with severe disease and prone to developing infections prophylactic use of antibiotics may reduce number of exacerbations and improve social and health care costs." ], "exact_answer": [ "Reduction of number of exacerbations" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029424", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000900", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019072", "http://www.disease-ontology.org/api/metadata/DOID:3083" ], "type": "factoid", "id": "515df063298dcd4e51000029", "snippets": [ { "offsetInBeginSection": 193, "offsetInEndSection": 657, "text": "Yet recent well-designed studies have demonstrated that prophylactic antibiotic use is of significant benefit to patients prone to developing infections. Study patients suffered from recurrent urinary tract infections, COPD or were mechanically ventilated in intensive care units. In the first 2 populations, use of antibiotics was associated with an increase in carriage of antibiotic-resistant bacteria, but in intensive care patients the opposite was documented", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22108462", "endSection": "sections.0" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1459, "text": "Guidelines do not recommend the use of prophylactic antibiotics in COPD but there is preliminary evidence to suggest that they may reduce the number of exacerbations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20477251", "endSection": "sections.0" }, { "offsetInBeginSection": 585, "offsetInEndSection": 784, "text": "A short prophylactic treatment course with azithromycin is a good alternative in the management of patients with severe, advanced COPD, and could lead to an improvement in social and healthcare costs", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11498704", "endSection": "sections.0" } ] }, { "body": "Has depression been shown to be a predictor of frailty?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9520923", "http://www.ncbi.nlm.nih.gov/pubmed/24314697", "http://www.ncbi.nlm.nih.gov/pubmed/18684366", "http://www.ncbi.nlm.nih.gov/pubmed/10855595", "http://www.ncbi.nlm.nih.gov/pubmed/11490597" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A15575023", "o": "797" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A15575023" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A7186488" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A17777767" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7186488", "o": "Frailty" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A7186488" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17777767", "o": "R54" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17777767", "o": "ICD-10-CM" } ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003866", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863" ], "type": "yesno", "id": "530cf57efe2466f70c000001", "snippets": [ { "offsetInBeginSection": 1457, "offsetInEndSection": 1560, "text": "significant role of frailty as a predictor of depression in a relatively younger old Chinese population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24314697", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1335, "text": "significant relationships between frailty and depressive symptoms and mortality at 1 year", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18684366", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1367, "text": "These findings suggest that malnutrition is a major predictor of frailty or the \"failure to thrive\" syndrome in older persons. Depression is a major cause of poor nutritional status in older persons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11490597", "endSection": "abstract" }, { "offsetInBeginSection": 2000, "offsetInEndSection": 2288, "text": "Depressed mood was associated with increased risk of steep strength decline, in particular in older men with low body weight. Low body weight in combination with depressed mood may be an indicator of frailty or severe disease status that leads to accelerated strength loss and disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10855595", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1198, "text": "Longitudinally, depressed mood was the only independent predictor of decline in cognition, functional ability, physician-rated health, and mortality;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9520923", "endSection": "abstract" } ] }, { "body": "What is the generic name of Gliolan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24468659", "http://www.ncbi.nlm.nih.gov/pubmed/22849976", "http://www.ncbi.nlm.nih.gov/pubmed/18389144", "http://www.ncbi.nlm.nih.gov/pubmed/25248327", "http://www.ncbi.nlm.nih.gov/pubmed/23870657" ], "ideal_answer": [ "5-aminolevulinic acid (or 5-ALA) is the generic name of Gliolan. It is approved for fluorescence-guided resections of adult malignant gliomas." ], "exact_answer": [ "5-aminolevulinic acid" ], "type": "factoid", "id": "54d73e223706e89528000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25248327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "OBJECTIVE: This study evaluates the cost-effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan\u00ae) in patients undergoing surgery for malignant glioma, in standard clinical practice conditions in Spain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24468659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "OBJECTIVE: To assess effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan(\u00ae)) in patients treated for malignant glioma under typical daily practice conditions in Spain, using complete resection rate (CR) and progression free survival at 6 months (PFS6). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23870657", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 585, "text": "Today, ALA is approved as Levulan for actinic keratoses, the ALA-methyl ester Metvix for actinic keratoses and basal cell carcinoma, the ALA-hexyl ester Hexvix for the diagnosis of bladder cancer and Gliolan for malignant glioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389144", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 850, "text": "MATERIAL AND METHODS: All patients who had undergone 5-ALA fluorescence-guided surgery due to suspected malignant glioma were included. Patients received a standard preoperative dose of Gliolan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22849976", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 583, "text": "Today, ALA is approved as Levulan for actinic keratoses, the ALA-methyl ester Metvix for actinic keratoses and basal cell carcinoma, the ALA-hexyl ester Hexvix for the diagnosis of bladder cancer and Gliolan for malignant glioma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389144", "endSection": "abstract" } ] }, { "body": "Is there any association between Jarid2 and miR-155 in Th17 cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "http://www.ncbi.nlm.nih.gov/pubmed/24950205" ], "ideal_answer": [ "Yes. Activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/JARD2_CHICK", "http://www.uniprot.org/uniprot/JARD2_HUMAN", "http://amigo.geneontology.org/amigo/term/GO:2000317", "http://www.uniprot.org/uniprot/JARD2_MOUSE", "http://amigo.geneontology.org/amigo/term/GO:0072538", "http://amigo.geneontology.org/amigo/term/GO:2000318", "http://amigo.geneontology.org/amigo/term/GO:2000316", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058504", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018417" ], "type": "yesno", "id": "56b8f28a156496395c000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Jarid2 links MicroRNA and chromatin in Th17 cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950205", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "In this issue of Immunity, Escobar et\u00a0al. (2014) bring microRNAs and chromatin together by showing how activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "title" }, { "offsetInBeginSection": 340, "offsetInEndSection": 1032, "text": "Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1122, "text": "Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1032, "text": "Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 1033, "text": "Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1033, "text": "Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "abstract" } ] }, { "body": "What is enCHIP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "http://www.ncbi.nlm.nih.gov/pubmed/25051498", "http://www.ncbi.nlm.nih.gov/pubmed/24201379" ], "ideal_answer": [ "Engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) is a novel method for purification of specific genomic regions retaining molecular interactions. EnChIP using the CRISPR system efficiently isolates specific genomic regions. In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins. enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047369" ], "type": "summary", "id": "56b2863945561f0573000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24201379", "endSection": "title" }, { "offsetInBeginSection": 148, "offsetInEndSection": 628, "text": "Here, we report isolation of telomeres by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using a transcription activator-like (TAL) protein recognizing telomere repeats. Telomeres recognized by the tagged TAL protein were immunoprecipitated with an antibody against the tag and subjected to identification of telomere-binding molecules. enChIP-mass spectrometry (enChIP-MS) targeting telomeres identified known and novel telomere-binding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24201379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 926, "text": "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. We showed that enChIP using the CRISPR system efficiently isolates specific genomic regions. In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins. enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 492, "text": "Recently, we developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology for purification of specific genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25051498", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 313, "text": "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 330, "text": "Recently, we developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology for purification of specific genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25051498", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 312, "text": "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 791, "text": "In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 406, "text": "Recently, we developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology for purification of specific genomic regions. Here, we developed a retroviral expression system for enChIP using CRISPR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25051498", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 406, "text": "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. We showed that enChIP using the CRISPR system efficiently isolates specific genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "abstract" } ] }, { "body": "How many genes does the human hoxD cluster contain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10364522", "http://www.ncbi.nlm.nih.gov/pubmed/22879880" ], "ideal_answer": [ "The human HOXD complex contains nine genes: HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12 and HOXD13, which are clustered from 3\u2032 to 5\u2032 in an approximately 100-kb stretch on chromosome 2q31.1 with HOXD1 at the 3' end and HOXD13 the 5\u2032 end." ], "exact_answer": [ "9" ], "type": "factoid", "id": "515db083298dcd4e51000012", "snippets": [ { "offsetInBeginSection": 699, "offsetInEndSection": 828, "text": "Both children are heterozygous for a deletion that eliminates at least eight (HOXD3-HOXD13) of the nine genes in the HOXD cluster", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10364522", "endSection": "sections.0" } ] }, { "body": "Is it safe to take isotretinoin during pregnancy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3209676", "http://www.ncbi.nlm.nih.gov/pubmed/18937624", "http://www.ncbi.nlm.nih.gov/pubmed/3459732", "http://www.ncbi.nlm.nih.gov/pubmed/23559397", "http://www.ncbi.nlm.nih.gov/pubmed/2923442", "http://www.ncbi.nlm.nih.gov/pubmed/17214828", "http://www.ncbi.nlm.nih.gov/pubmed/21198520", "http://www.ncbi.nlm.nih.gov/pubmed/7962395", "http://www.ncbi.nlm.nih.gov/pubmed/19961047", "http://www.ncbi.nlm.nih.gov/pubmed/12171680", "http://www.ncbi.nlm.nih.gov/pubmed/2102396", "http://www.ncbi.nlm.nih.gov/pubmed/9439011", "http://www.ncbi.nlm.nih.gov/pubmed/9035347", "http://www.ncbi.nlm.nih.gov/pubmed/20436882", "http://www.ncbi.nlm.nih.gov/pubmed/3162101", "http://www.ncbi.nlm.nih.gov/pubmed/3162748", "http://www.ncbi.nlm.nih.gov/pubmed/11445913", "http://www.ncbi.nlm.nih.gov/pubmed/15545101", "http://www.ncbi.nlm.nih.gov/pubmed/3501432", "http://www.ncbi.nlm.nih.gov/pubmed/9091512", "http://www.ncbi.nlm.nih.gov/pubmed/9299599", "http://www.ncbi.nlm.nih.gov/pubmed/1473624" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugbank/description", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00982", "o": "Isotretinoin is a medication used for the treatment of severe acne. It is sometimes used in prevention of certain skin cancers. It is a retinoid, meaning it derives from vitamin A and is found in small quantities naturally in the body. Isotretinoin binds to and activates nuclear retinoic acid receptors (RAR), thereby regulating cell proliferation and differentiation. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization." }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11572307", "o": "FDA Structured Product Labels" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12802988", "o": "Isotretinoin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17902718", "o": "National Drug File - Reference Terminology" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0022265", "o": "http://linkedlifedata.com/resource/umls/label/A17902718" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Isotretinoin", "o": "Isotretinoin" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0599177", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17035190", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A18361057", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10769142", "o": "ISOTRETINOIN" } ], "ideal_answer": [ "No. The isotretinoin has severe teratogenic effects and it is not safe to use during pregnancy." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0007565", "http://www.biosemantics.org/jochem#4165261", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015474", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011259", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061685" ], "type": "yesno", "id": "51640b4a298dcd4e51000050", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559397", "endSection": "sections.0" }, { "offsetInBeginSection": 134, "offsetInEndSection": 185, "text": "a number of important adverse effects were reported", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559397", "endSection": "sections.0" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1483, "text": "even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559397", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 75, "text": "Isotretinoin has revolutionized the management of acne vulgaris.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21198520", "endSection": "sections.0" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1383, "text": "The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21198520", "endSection": "sections.0" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1369, "text": "Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436882", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "The isotretinoin, a 13-cis-retinoic acid, has revolutionized the management of severe treatment-resistant acne and it has been widely used for a range of dermatological conditions, in 90% of the time in young women between 13 and 45 years of age. This agent has severe teratogenic effects, as serious craniofacial, cardiovascular, thymic and central nervous system malformations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961047", "endSection": "sections.0" }, { "offsetInBeginSection": 412, "offsetInEndSection": 757, "text": "malformations is 3-5%, but it increases to almost 30% in women exposed to isotretinoin during the first trimester of pregnancy. Generally, patients in treatment with isotretinoin avoid eventual pregnancy during assumption and, after its stopping, fertility and foetal development are normal once circulating isotretinoin levels return to normal.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961047", "endSection": "sections.0" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1491, "text": "After 3 months of pharmacological wash out, patient become pregnant and manifested this severe malformation. Woman interrupted gestation, by labour induction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961047", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18937624", "endSection": "sections.0" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1186, "text": "Safety of CTG use in pregnancy has not been established.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18937624", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 224, "text": "To estimate the population-based incidence rates of pregnancy, spontaneous and elective abortions, and birth defects associated with isotretinoin use, and to determine predictors of pregnancy while on isotretinoin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17214828", "endSection": "sections.0" }, { "offsetInBeginSection": 706, "offsetInEndSection": 833, "text": "Pregnancies, spontaneous and elective abortions, and birth defects were identified using procedure codes and medical diagnoses.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17214828", "endSection": "sections.0" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1347, "text": "90 women who became pregnant while on the drug, 76 terminated the pregnancy (84%), three had a spontaneous abortion (3%), two had trauma during delivery resulting in neonatal deaths (2%) and nine had a live birth (10%). Among the live births, only one had a congenital anomaly of the face and neck (11%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17214828", "endSection": "sections.0" }, { "offsetInBeginSection": 1870, "offsetInEndSection": 1929, "text": "elective abortion rates were also much higher in our study.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17214828", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 346, "text": "Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15545101", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 211, "text": "Isotretinoin has been used to treat acne since 1982. Its current indications in the package insert are limited and many physicians still feel uncomfortable prescribing it because of its side effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171680", "endSection": "sections.0" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1189, "text": "Aside from its teratogenic effect, isotretinoin is a safe and excellent drug for acne therapy. I", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171680", "endSection": "sections.0" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1375, "text": "a pregnancy test in females.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171680", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11445913", "endSection": "sections.0" }, { "offsetInBeginSection": 463, "offsetInEndSection": 905, "text": "Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11445913", "endSection": "sections.0" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1272, "text": "The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11445913", "endSection": "sections.0" }, { "offsetInBeginSection": 123, "offsetInEndSection": 335, "text": "Isotretinoin (13-cis-RA) is teratogenic in all species examined; based on administered dose, humans appear most sensitive, followed by (in order or decreasing sensitivity) monkey, rabbit, hamster, mouse, and rat.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9299599", "endSection": "sections.0" }, { "offsetInBeginSection": 2575, "offsetInEndSection": 2685, "text": "Based on embryonic delivered dose, we suggest that 13-cis-RA is an equipotent teratogen in hamster and rabbit.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9299599", "endSection": "sections.0" }, { "offsetInBeginSection": 153, "offsetInEndSection": 296, "text": "its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9091512", "endSection": "sections.0" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1197, "text": "topical tretinoin is not a potential human developmental toxicant.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9091512", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 402, "text": "Teratogenicity of vitamin A was firstly detected in experimental animals in 1953. Nearly 30 years later, teratogenicity of vitamin A analogue-isotretinoin was reported in humans. Isotretinoin induces serious birth defects of craniofacial and central nervous system, cardiovascular system and thymic malformations--in about 25% of babies exposed during the first trimester of their prenatal development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9439011", "endSection": "sections.0" }, { "offsetInBeginSection": 526, "offsetInEndSection": 713, "text": "high vitamin A intake in pregnant woman: Women who use daily vitamin A supplements during early pregnancy have approximately a two-fold increased risk of giving birth to a malformed baby.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9439011", "endSection": "sections.0" }, { "offsetInBeginSection": 1377, "offsetInEndSection": 1576, "text": "Vitamin A started to affect development between doses 0.3-0.3 microm [corrected] per embryo. Malformations of head, extremities and heart were detected similarly like in laboratory mammals and in man", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9439011", "endSection": "sections.0" }, { "offsetInBeginSection": 1875, "offsetInEndSection": 1988, "text": "the minimal embryotoxic doses of vitamin A in mammals were estimated to be between 0.1-1 mg/kg of maternal weight", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9439011", "endSection": "sections.0" }, { "offsetInBeginSection": 2060, "offsetInEndSection": 2665, "text": "Human epidemiological studies have proved teratogenicity of vitamin A after daily doses 25,000 i.u.-8.3 mg (0.13 mg/kg)- and reduction of its maximum intake has been recommended to 10,000 i.u. per day (0.05 mg/kg). The results about teratogenicity of vitamin A achieved in the chick embryo are in agreement with such a recommendation. Intake of vitamin A in the food is sufficient for pregnant woman in common Czech population. Therefore, an artificial supplementation of vitamin A brings risk of overdosage. If supplementation by vitamin A is unavoidable during pregnancy, B-carotene should be preferred.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9439011", "endSection": "sections.0" }, { "offsetInBeginSection": 461, "offsetInEndSection": 551, "text": "a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193].", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9035347", "endSection": "sections.0" }, { "offsetInBeginSection": 2942, "offsetInEndSection": 3397, "text": "plasma AUC values of all-trans-RA were 2- to 7-fold higher after all-trans-RA administration (present study) than after dosing with the teratogenic dose of 13-cis-RA. These results strengthen our recent suggestion that the teratogenic effects induced in cynomolgus monkeys by 13-cis-RA treatment cannot solely result from the action of all-trans-RA, but may involve 13-cis-RA and 13-cis-4-oxo-RA, which could act directly or function as transport vehicle.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9035347", "endSection": "sections.0" }, { "offsetInBeginSection": 128, "offsetInEndSection": 346, "text": "VITA, among others, is involved in the process of morphogenesis. In contrast, synthetic derivatives of VITA, specifically Tigasone (etretinate, TIG) and Roaccutane (isotretinoin, ROA), are regarded as major teratogens.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7962395", "endSection": "sections.0" }, { "offsetInBeginSection": 706, "offsetInEndSection": 1087, "text": "A biphasic maximal inhibition was present at 1 microM concentrations when the retinoids VITA, TIG and ROA were added for 16 h (52, 58 and 57%, respectively; P < 0.01 by one-way analysis of variance). In contrast, the addition of the three retinoids at 1 microM concentrations for 16 h had no significant effect on HCG secretion by placental explants of 11-13 weeks gestational age.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7962395", "endSection": "sections.0" }, { "offsetInBeginSection": 1321, "offsetInEndSection": 1431, "text": "Inhibition of HCG secretion by retinoids may contribute either directly or indirectly to their teratogenicity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7962395", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1473624", "endSection": "sections.0" }, { "offsetInBeginSection": 390, "offsetInEndSection": 477, "text": "defects that includes heart defects, by inhibiting the migration of neural crest cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1473624", "endSection": "sections.0" }, { "offsetInBeginSection": 656, "offsetInEndSection": 804, "text": "Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1473624", "endSection": "sections.0" }, { "offsetInBeginSection": 1410, "offsetInEndSection": 1619, "text": "The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1473624", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 606, "text": "Oral administration of 400 mg/kg of 13-cis retinoic acid to 9 day pregnant mice gives rise to important maxillofacial malformations. The first manifestation of teratogenic effect is an increase of density of cell death arising in the dorsal part of the first two branchial arches at day 9.5. These two arches become hypoplastic at days 10 and 11, and the preskeletal anlagen appear too late in comparison to control embryos. Meckel's cartilage is too curvilinear and medially situated. Pre-ossicular and pre-mandibular blastemata develop with spatial distortions which are well analyzable at days 16 and 17", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2102396", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Isotretinoin (13-cis-retinoic acid, Accutane) increases the risk of major congenital malformations in infants exposed to isotretinoin during pregnancy. However, there have been no epidemiologic reports to date on the effect of a subsequent pregnancy after discontinuation of isotretinoin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2923442", "endSection": "sections.0" }, { "offsetInBeginSection": 316, "offsetInEndSection": 443, "text": "analysis of pregnancy case reports from patients in whom conception occurred after isotretinoin treatment had been discontinued", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2923442", "endSection": "sections.0" }, { "offsetInBeginSection": 521, "offsetInEndSection": 699, "text": "spontaneous and missed abortions from all pregnancies was 9.1% (eight patients), and the incidence rate of congenital malformation among the live births was 5.0% (four patients).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2923442", "endSection": "sections.0" }, { "offsetInBeginSection": 744, "offsetInEndSection": 968, "text": "were not significantly different from the rates reported for women of reproductive age in the general population. In addition, the malformations reported were not characteristic of retinoic acid-induced congenital anomalies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2923442", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Keratolenticular dysgenesis (Peters' anomaly) was induced in mice by exposure to the human teratogens, ethanol or 13-cis retinoic acid (isotretinoin, Accutane). Acute teratogen exposure on the seventh day of gestation (corresponding to the third week of human gestation) resulted in an eye malformation incidence of 46% to 100% in day 14 fetuses", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3162748", "endSection": "sections.0" }, { "offsetInBeginSection": 706, "offsetInEndSection": 904, "text": "This secondary effect on neural crest derivatives is exhibited in the adult animals as corneal opacities associated with defects in Descemet's membrane and endothelium, and anterior polar cataracts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3162748", "endSection": "sections.0" }, { "offsetInBeginSection": 38, "offsetInEndSection": 173, "text": "13-cis-retinoic acid (13-cis-RA, or isotretinoin) is responsible for various craniofacial malformations in the rodent and human embryo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3209676", "endSection": "sections.0" }, { "offsetInBeginSection": 290, "offsetInEndSection": 440, "text": "In whole embryo culture, 13-cis-RA caused significant overall embryonic growth retardation, especially in the primary and secondary palatal processes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3209676", "endSection": "sections.0" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1498, "text": "subsequent cell growth was decreased at concentrations of 13-cis-RA greater than 1 X 10(-5) M. After a 40-hr treatment period, labeling indices in retinoid-treated cells were significantly lower than control values (25% compared with 40%). Retinoic acid also caused a significant, concentration-dependent decrease in 3H-thymidine incorporation. The inhibitory effect of 13-cis-RA on proliferation of oral-nasal mesenchymal cells appears to be related to the production of craniofacial malformations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3209676", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Reports of adverse human pregnancy outcomes including cleft palate have increased as the clinical use of isotretinoin (13-cis-retinoic acid) and other retinoic acid (RA) derivatives have increased, but the mechanisms by which their effects are exerted are not understood.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3501432", "endSection": "sections.0" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1827, "text": "In shelves exposed to EGF and trans-RA early in their development, DNA synthesis appears to terminate prematurely as compared to shelves cultured in control media, and this effect is accompanied by excessive mesenchymal extracellular space expansion. Exposure of shelves to EGF alone is sufficient to block degeneration and induce hyperplasia of the medial epithelial cells but does not induce other ultrastructural changes seen with both EGF and RA. The observed alterations in medial cell morphology could interfere with adhesion of the palatal shelves and may play a role in retinoid-induced cleft palate in the human embryo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3501432", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Recent clinical observations strongly suggest that isotretinoin [13-cis-retinoic acid (cis RA)] is a human teratogen causing primarily heart and craniofacial malformations including ear and palatal defects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3459732", "endSection": "sections.0" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1699, "text": "Our results demonstrate that labeled cis RA enters the tissues of the embryo both in vivo and in vitro. Cis RA inhibited proliferation of the frontonasal mesenchyme cells in primary culture with 31% inhibition occurring at 2 X 10(-5) M cis RA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3459732", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 536, "text": "Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3162101", "endSection": "sections.0" }, { "offsetInBeginSection": 639, "offsetInEndSection": 830, "text": "Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3162101", "endSection": "sections.0" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1568, "text": "It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3162101", "endSection": "sections.0" } ] }, { "body": "Which protein is the E3-ubiquitin ligase that targets the tumor suppressor p53 for proteasomal degradation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22666487", "http://www.ncbi.nlm.nih.gov/pubmed/16082221", "http://www.ncbi.nlm.nih.gov/pubmed/22819825", "http://www.ncbi.nlm.nih.gov/pubmed/23150437", "http://www.ncbi.nlm.nih.gov/pubmed/11948425", "http://www.ncbi.nlm.nih.gov/pubmed/12832479", "http://www.ncbi.nlm.nih.gov/pubmed/21075307", "http://www.ncbi.nlm.nih.gov/pubmed/15632057", "http://www.ncbi.nlm.nih.gov/pubmed/19934289", "http://www.ncbi.nlm.nih.gov/pubmed/18235222", "http://www.ncbi.nlm.nih.gov/pubmed/24174547", "http://www.ncbi.nlm.nih.gov/pubmed/15013777", "http://www.ncbi.nlm.nih.gov/pubmed/19166840", "http://www.ncbi.nlm.nih.gov/pubmed/16339144", "http://www.ncbi.nlm.nih.gov/pubmed/23671280", "http://www.ncbi.nlm.nih.gov/pubmed/23581014" ], "ideal_answer": [ "The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2). The RING domain E3 ubiquitin ligase Mdm2 is the master regulator of the tumor suppressor p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation.", "This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development., p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation., Mdm2 has been thought to regulate the tumor suppressor p53 in two ways: by masking p53's access to transcriptional machinery, and by ubiquitinating p53, targeting it for proteasomal degradation" ], "exact_answer": [ "The mouse double minute 2 (mdm2)", "The human homologue of Mdm2 (Hdm2)" ], "type": "factoid", "id": "55058af6f73303d458000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "p53 levels and activity are controlled in large part through regulated ubiquitination and subsequent destruction by the 26S proteasome. Monoubiquitination of p53 is mediated primarily by the RING-finger E3 ubiquitin ligase MDM2 and impacts p53 activity through modulation of p53 localization and transcription activities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "The RING domain E3 ubiquitin ligase Mdm2 is the master regulator of the tumor suppressor p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23671280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "The p53 transcription factor and tumor suppressor is regulated primarily by the E3 ubiquitin ligase Mdm2, which ubiquitinates p53 to target it for proteasomal degradation. Aside from its ubiquitin ligase function, Mdm2 has been believed to be capable of suppressing p53's transcriptional activity by binding with and masking the transactivation domain of p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22666487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "The regulation of p53 expression levels is critical in controlling p53 activity in normal and damaged cells. This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23581014", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 232, "text": "p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19934289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 530, "text": "Mdm2 has been thought to regulate the tumor suppressor p53 in two ways: by masking p53's access to transcriptional machinery, and by ubiquitinating p53, targeting it for proteasomal degradation. This dogma was recently challenged by data generated from knockin mice in which Mdm2's RING E3 ubiquitin ligase activity was abrogated by a single point mutation. The RING mutant Mdm2 is fully capable of binding with p53, yet cannot suppress p53 activity, suggesting that Mdm2 cannot block p53 by binding alone, without ubiquitination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18235222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "MDM2 is an E3 ubiquitin ligase that regulates the proteasomal degradation and activity of proteins involved in cell growth and apoptosis, including the tumor suppressors p53 and retinoblastoma and the transcription factor E2F1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "The p53 tumor suppressor protein has a major role in protecting genome integrity. Under normal circumstances Mdmx and Mdm2 control the activity of p53. Both proteins inhibit the transcriptional regulation by p53, while Mdm2 also functions as an E3 ubiquitin ligase to target both p53 and Mdmx for proteasomal degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16082221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 515, "text": "p53 is a critical coordinator of a wide range of stress responses. To facilitate a rapid response to stress, p53 is produced constitutively but is negatively regulated by MDM2. MDM2 can inhibit p53 in multiple independent ways: by binding to its transcription activation domain, inhibiting p53 acetylation, promoting nuclear export, and probably most importantly by promoting proteasomal degradation of p53. The latter is achieved via MDM2's E3 ubiquitin ligase activity harbored within the MDM2 RING finger domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15632057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Mdm2 is a RING finger E3 ubiquitin ligase, which promotes ubiquitination and proteasomal degradation of the p53 tumor suppressor protein. Acetylation of p53 regulates p53's transcriptional activity and inhibits Mdm2-mediated p53 ubiquitination and degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15013777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "MDM2 is an E3 ubiquitin ligase that targets p53 for proteasomal degradation. Recent studies have shown, however, that the ring-finger domain (RFD) of MDM2, where the ubiquitin E3 ligase activity resides, is necessary but not sufficient for p53 ubiquitination, suggesting that an additional activity of MDM2 might be required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "The Mdm2 proto-oncogene is amplified and over-expressed in a variety of tumors. One of the major functions of Mdm2 described to date is its ability to modulate the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N-terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53 for rapid proteasomal degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11948425", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 450, "text": "The HDM2-p53 loop is crucial for monitoring p53 level and human pathologies. Therefore, identification of novel molecules involved in this regulatory loop is necessary for understanding the dynamic regulation of p53 and treatment of human diseases. Here, we characterized that the ribosomal protein L6 binds to and suppresses the E3 ubiquitin ligase activity of HDM2, and subsequently attenuates HDM2-mediated p53 polyubiquitination and degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24174547", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1399, "text": "Together, our study identifies the crucial function of RPL6 in regulating HDM2-p53 pathway, which highlights the importance of RPL6 in human genetic diseases and cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24174547", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 356, "text": "Targeting the E3 ubiquitin ligase HDM2 can lead to a therapeutic surge in p53 levels. However, the efficacy of HDM2 inhibition can be compromised by overexpression of HDMX, an HDM2 homolog that binds and sequesters p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21075307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a negative feedback loop. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19166840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Murine double minute (MDM2) is an E3 ligase that promotes ubiquitination and degradation of tumor suppressor protein 53 (p53).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819825", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 300, "text": "This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23581014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Mdm2 is a RING finger E3 ubiquitin ligase, which promotes ubiquitination and proteasomal degradation of the p53 tumor suppressor protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15013777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "MDM2 is an E3 ubiquitin ligase that regulates the proteasomal degradation and activity of proteins involved in cell growth and apoptosis, including the tumor suppressors p53 and retinoblastoma and the transcription factor E2F1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The p53 transcription factor and tumor suppressor is regulated primarily by the E3 ubiquitin ligase Mdm2, which ubiquitinates p53 to target it for proteasomal degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22666487", "endSection": "abstract" } ] }, { "body": "Can DNA intercalators function as topoisomerase inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23495154", "http://www.ncbi.nlm.nih.gov/pubmed/2820967", "http://www.ncbi.nlm.nih.gov/pubmed/3002440", "http://www.ncbi.nlm.nih.gov/pubmed/8242865", "http://www.ncbi.nlm.nih.gov/pubmed/2168281", "http://www.ncbi.nlm.nih.gov/pubmed/10691026", "http://www.ncbi.nlm.nih.gov/pubmed/21591994", "http://www.ncbi.nlm.nih.gov/pubmed/7525959", "http://www.ncbi.nlm.nih.gov/pubmed/3009009", "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "http://www.ncbi.nlm.nih.gov/pubmed/18043127", "http://www.ncbi.nlm.nih.gov/pubmed/19424733", "http://www.ncbi.nlm.nih.gov/pubmed/17433851", "http://www.ncbi.nlm.nih.gov/pubmed/10637356", "http://www.ncbi.nlm.nih.gov/pubmed/11077044", "http://www.ncbi.nlm.nih.gov/pubmed/17442658", "http://www.ncbi.nlm.nih.gov/pubmed/8941714", "http://www.ncbi.nlm.nih.gov/pubmed/2157558", "http://www.ncbi.nlm.nih.gov/pubmed/8449832", "http://www.ncbi.nlm.nih.gov/pubmed/2164630", "http://www.ncbi.nlm.nih.gov/pubmed/1727386", "http://www.ncbi.nlm.nih.gov/pubmed/10434060", "http://www.ncbi.nlm.nih.gov/pubmed/2695099", "http://www.ncbi.nlm.nih.gov/pubmed/22304499", "http://www.ncbi.nlm.nih.gov/pubmed/11230801", "http://www.ncbi.nlm.nih.gov/pubmed/8812219", "http://www.ncbi.nlm.nih.gov/pubmed/2845248", "http://www.ncbi.nlm.nih.gov/pubmed/22975492", "http://www.ncbi.nlm.nih.gov/pubmed/16798938", "http://www.ncbi.nlm.nih.gov/pubmed/20133050", "http://www.ncbi.nlm.nih.gov/pubmed/2537142", "http://www.ncbi.nlm.nih.gov/pubmed/367540", "http://www.ncbi.nlm.nih.gov/pubmed/21446672", "http://www.ncbi.nlm.nih.gov/pubmed/9619832" ], "ideal_answer": [ "The DNA unwinding suggests DNA intercalation, which could explain the inhibition of topoisomerase II. Among its many properties, amiloride is a DNA intercalator and topoisomerase II inhibitor. Amsacrine, a DNA intercalator and topoisomerase II inhibitor, is efficacious as an antileukemogenic agent. AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator. Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026942", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059004", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059005", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004264", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004250" ], "type": "yesno", "id": "56c71cb65795f9a73e00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "The aporphine alkaloids (+)-dicentrine and (+)-bulbocapnine are non-planar molecules lacking features normally associated with DNA binding by intercalation or minor groove binding. Surprisingly, dicentrine showed significant activity as a topoisomerase II (EC 5.99.1.3) inhibitor and also was active in a DNA unwinding assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11230801", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 427, "text": "The DNA unwinding suggests DNA intercalation, which could explain the inhibition of topoisomerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11230801", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 605, "text": "We found that several agents, including adriamycin (a DNA intercalator and inhibitor of topoisomerase II)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9619832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Amsacrine, a DNA intercalator and topoisomerase II inhibitor, is efficacious as an antileukemogenic agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8812219", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1544, "text": "Quinacrine was less effective. (ii) Inhibitors intercalating and binding to the 'cleavable' DNA-topoisomerase complex (m-AMSA, mitoxantrone, doxorubicin and daunorubicin) strongly suppressed reparative DNA incision. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8242865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "DNA intercalation and inhibition of topoisomerase II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Among its many properties, amiloride is a DNA intercalator and topoisomerase II inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 459, "text": "To determine whether the ability of amiloride to intercalate into DNA and to inhibit DNA topoisomerase II was dependent on the ability to assume a cyclized conformation, we studied the structure-activity relationship for 12 amiloride analogs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 890, "text": "Empirical assays consisting of biophysical, biochemical, and cell biological approaches, as well as computational molecular modeling approaches, were used to determine conformational properties for these molecules, and to determine whether they intercalated into DNA and inhibited topoisomerase II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "endSection": "abstract" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1590, "text": "Results indicated that only those analogs capable of cyclization could intercalate into DNA and inhibit topoisomerase II. Thus, the ability of amiloride and the 12 analogs studied to intercalate into DNA and to inhibit topoisomerase II appears dependent on the ability to exist in a planar, hydrogen-bonded, tricyclic conformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Abnormal expression of the nuclear-associated enzyme DNA topoisomerase II (topoisomerase II) has been implicated in the in vitro phenotype of radiation hypersensitive ataxia-telangiectasia (A-T) cells and in modifying sensitivity of eukaryotic cells to topoisomerase II-inhibitor drugs [e.g., the DNA intercalator amsacrine (mAMSA)]. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2537142", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 448, "text": "All three tested anthraquinones, emodin, aloe-emodin, and danthron, showed capabilities to inhibit the non-covalent binding of bisbenzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells comparable to the topoisomerase II inhibitor and intercalator m-amsacrine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10434060", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1195, "text": "These studies suggest that AD 288 inhibits topoisomerase II activity by preventing the initial non-covalent binding of topoisomerase II to DNA. Since AD 288 is a potent DNA intercalator, catalytic inhibition is achieved by prohibiting access of the enzyme to DNA binding sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11077044", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 248, "text": "AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17442658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18043127", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1152, "text": " We found that three compounds had similar cancer cell-selective growth inhibition to amonafide, while retaining similar subcellular localization, DNA intercalation and topoisomerase II inhibition activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18043127", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 168, "text": "Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21591994", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 718, "text": "At higher concentrations, inhibition of Top1 catalytic activity and DNA intercalation is observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16798938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17433851", "endSection": "title" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1514, "text": "It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (but not doxorubicin) stimulated DNA topoisomerase I-induced cleavage at specific DNA sites; 2) only doxorubicin and Actinomycin D stimulated DNA cleavage by DNA topoisomerase II; 3) at higher drug concentrations, DNA intercalators suppressed enzyme-mediated DNA cleavage induced by DNA topoisomerase I, as well as topoisomerase II; 4) only cyanomorpholinyldoxorubicin produced DNA-DNA cross-links; no DNA unwinding could be observed; and 5) DNA intercalation (unwinding) potency of morpholinyldoxorubicin was about 2-fold less than that of doxorubicin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2164630", "endSection": "abstract" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1129, "text": "The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2164630", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1149, "text": "The screen of cMAP for uncharacterized drugs indicated the signature of Epoxy anthraquinone derivative (EAD) matched the profiles of multiple known DNA targeted agents (topoisomerase I/II inhibitors, DNA intercalators, and DNA alkylation agents) as predicted by its structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20133050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Cytotoxicity of several classes of antitumor DNA intercalators is thought to result from disturbance of DNA metabolism following trapping of the nuclear enzyme DNA topoisomerase II as a covalent complex on DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8941714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3009009", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 612, "text": "Many compounds capable of inhibiting DNA topoisomerase II are DNA intercalators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2820967", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 799, "text": "Numerous topoisomerase I poisons including DNA minor groove binders such as Hoechst 33258 and DNA intercalators such as benzophenanthridine alkaloids and indolocarbazole derivatives have been discovered and developed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10637356", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1275, "text": "The stabilization of cleavage intermediates by intercalators may have a common mechanism for DNA topoisomerase I and DNA topoisomerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2164630", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 613, "text": "Because structurally related antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19424733", "endSection": "abstract" }, { "offsetInBeginSection": 1665, "offsetInEndSection": 1935, "text": "Taken together, our results suggest that much of the activity and specificity of m-AMSA as a topoisomerase II poison is embodied in the headgroup, while DNA intercalation is used primarily to increase the affinity of m-AMSA for the topoisomerase II-DNA cleavage complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22304499", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 1080, "text": "The cross-sensitivity patterns of the mutant were examined for covalently (anthramycin) and non-covalently (distamycin A) binding minor groove ligands, and DNA intercalating [adriamycin, mitoxantrone and 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA)] and non-intercalating (VP16-213) topoisomerase II poisons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2157558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Quinoline alkaloids as intercalative topoisomerase inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19424733", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "DNA intercalation and inhibition of topoisomerase II. Structure-activity relationships for a series of amiloride analogs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "endSection": "title" }, { "offsetInBeginSection": 1835, "offsetInEndSection": 2260, "text": "These include: (i) the production of improved topoisomerase inhibitors (by consideration of drug/protein as well as drug/DNA interactions); (ii) the development of reductively-activated chromophores as hypoxia-selective agents; and (iii) the use of DNA-intercalators of known DNA binding orientation as 'carriers' for the delivery of other reactive functionality specifically (sequence-, regio- and site-specifically) to DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2695099", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 486, "text": "Indolo[2,3-b]quinolines are a family of DNA intercalators and inhibitors of topoisomerase II, synthetic analogs of neocryptolepine, an alkaloid traditionally used in African folk medicine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975492", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 707, "text": "Their ability to function as bis-intercalators was assessed by a novel and convenient topoisomerase fluorescent assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/367540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Structure-activity relationship of polypyridyl ruthenium(II) complexes as DNA intercalators, DNA photocleavage reagents, and DNA topoisomerase and RNA polymerase inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23495154", "endSection": "title" }, { "offsetInBeginSection": 826, "offsetInEndSection": 1121, "text": "In addition, fragments of about 900 kbp were detected in the cells treated with a topoisomerase inhibitor, 4'-(9-acridinylamino)methane-sulfon-m-anisidine, and fragments in the broad size range between 700 and 245 kbp in the cells treated with radical producers, bleomycin and neocarzinostatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8449832", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1003, "text": "The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2164630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Long-term inhibition of DNA synthesis and the persistence of trapped topoisomerase II complexes in determining the toxicity of the antitumor DNA intercalators mAMSA and mitoxantrone.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2168281", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Effects of the DNA intercalators 4'-(9-acridinylamino)methanesulfon-m-anisidide and 2-methyl-9-hydroxyellipticinium on topoisomerase II mediated DNA strand cleavage and strand passage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3002440", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3009009", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 422, "text": "Here, molecular interactions of the potent antitumor drug amsacrine (m-AMSA), an inhibitor of topoisomerase II, within living K562 cancer cells have been studied using surface-enhanced Raman (SER) spectroscopy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8941714", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 336, "text": "It has been shown previously that DNA intercalators can inhibit the action of amsacrine and several other topoisomerase II poisons, presumably as a result of interference with the DNA binding sites for the enzyme. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10691026", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1102, "text": "The gadd153 promoter was strongly activated by a broad spectrum of genotoxic agents including UV-mimetic agents, DNA-cross-linking and alkylating agents, DNA intercalators, and topoisomerase inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1727386", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1536, "text": "Our study indicates that Epoxy anthraquinone derivative may be a novel DNA topoisomerase inhibitor that can be potentially used for treatment of neuroblastoma or other cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20133050", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 386, "text": "Organic intercalators can inhibit nucleic acid synthesis in vivo, and they are now common anticancer drugs in clinical therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21446672", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 355, "text": "Because structurally related antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19424733", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1381, "text": "Specifically, we measured the ability of these compounds to 1) alter the thermal denaturation profile of DNA, 2) modify the hydrodynamic behavior of DNA, 3) inhibit the catalytic activity of purified DNA topoisomerase II in vitro, 4) promote the topoisomerase II-dependent cleavage of DNA, and 5) inhibit functions associated with DNA topoisomerase II in intact cells. Results indicated that only those analogs capable of cyclization could intercalate into DNA and inhibit topoisomerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "A function for topoisomerases I and II in DNA excision repair can be postulated from the organization of the mammalian chromosome, involving nucleosomal structures and matrix-attached DNA loops. To analyse this function we determined UV-induced DNA incision in confluent human fibroblasts in the presence of 16 inhibitors of topoisomerases I and II which belonged to at least five different drug categories, based on their mechanism of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8242865", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 536, "text": "In experiments to determine the mechanism of inhibition of DNA synthesis by amiloride, we observed that amiloride inhibited both the catalytic activity of purified DNA topoisomerase II in vitro and DNA topoisomerase II-dependent cell functions in vivo. Many compounds capable of inhibiting DNA topoisomerase II are DNA intercalators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2820967", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 1003, "text": "The pyridoacridines' ability to inhibit TOPO II-mediated decatenation of kDNA correlated with their cytotoxic potencies and their ability to intercalate into calf thymus DNA. These results suggest that disruption of the function of TOPO II, subsequent to intercalation, is a probable mechanism by which pyridoacridines inhibit the proliferation of HCT cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7525959", "endSection": "abstract" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1463, "text": "Evidence for DNA intercalation by AD41 is provided by the observation that the drug introduces positive supercoils into covalently closed plasmid DNA. Based on these data, a hypothesis is proposed that would provide a general mechanism whereby intercalating agents and epipodophyllotoxins alter topoisomerase function and presumably exert their antitumor effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2845248", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 990, "text": "Therefore, to more fully analyze structure-function relationships and the role of DNA binding in the action of m-AMSA, we analyzed a series of derivatives for the ability to enhance DNA cleavage mediated by human topoisomerase II\u03b1 and topoisomerase II\u03b2 and to intercalate DNA. Results indicate that the 3'-methoxy (m-AMSA) positively affects drug function, potentially by restricting the rotation of the headgroup in a favorable orientation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22304499", "endSection": "abstract" } ] }, { "body": "Which diseases is microRNA 132 (miR-132) implicated in?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22659469", "http://www.ncbi.nlm.nih.gov/pubmed/23560086", "http://www.ncbi.nlm.nih.gov/pubmed/22315408", "http://www.ncbi.nlm.nih.gov/pubmed/22518321", "http://www.ncbi.nlm.nih.gov/pubmed/23001356", "http://www.ncbi.nlm.nih.gov/pubmed/21807765", "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "http://www.ncbi.nlm.nih.gov/pubmed/21136867", "http://www.ncbi.nlm.nih.gov/pubmed/17314675", "http://www.ncbi.nlm.nih.gov/pubmed/20949564", "http://www.ncbi.nlm.nih.gov/pubmed/23485811", "http://www.ncbi.nlm.nih.gov/pubmed/23269581" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A18453276", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0015570" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0015570", "o": "MeSH" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17694181", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A7568412", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "Several targets for for miR-132 have been described and it is implicated in many diseases such as:\nneurodegenerative disease, \nepilepsy,\nschizophrenia,\nHuntington's disease (HD),\nAlzheimer's disease (AD),\nneuroinflammation,\nosteosarcoma,\nchronic lymphocytic leukemia (CLL),\nangiogenesis,\neye disease,\nalcoholic liver disease,\nprogressive supranuclear palsy (PSP taupathy),\nmild cognitive impairment." ], "exact_answer": [ [ "neurodegenerative disease" ], [ "epilepsy" ], [ "schizophrenia" ], [ "Huntington's disease (HD)" ], [ "Alzheimer's disease (AD)" ], [ "neuroinflammation" ], [ "osteosarcoma" ], [ "chronic lymphocytic leukemia (CLL)" ], [ "angiogenesis" ], [ "eye disease" ], [ "alcoholic liver disease" ], [ "progressive supranuclear palsy (PSP taupathy)" ], [ "mild cognitive impairment" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007905", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020734", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030342", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006816", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002908", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005128", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "list", "id": "5156be75d24251bc05000088", "snippets": [ { "offsetInBeginSection": 588, "offsetInEndSection": 901, "text": "Levels of six candidate miRNAs (miR-21, miR-199a-3p, miR-143, miR-34, miR-140, and miR-132) that were previously demonstrated to be regulated in osteosarcoma were examined in plasma of 40 osteosarcoma patients and 40 matched healthy controls by quantitative reverse-transcription polymerase chain reaction assays.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23269581", "endSection": "sections.0" }, { "offsetInBeginSection": 1538, "offsetInEndSection": 2044, "text": "Functional studies employing antagomirs have identified contributions from miR-34a and miR-132 to seizure-induced neuronal death whereas silencing miR-134 potently reduced status epilepticus, seizure-damage and the later occurrence of spontaneous seizures. Efforts to identify the in vivo target(s) of epilepsy-regulated miRNAs, is now a priority. Last, miRNA are stable, information-carrying (paracrine) signals. Profiling miRNA in biofluids may represent a novel source of disease biomarkers in epilepsy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23485811", "endSection": "sections.0" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1265, "text": "Inflammation, stress signalling and neuronal excitation are among the pathways most impacted.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23485811", "endSection": "sections.0" }, { "offsetInBeginSection": 119, "offsetInEndSection": 469, "text": "Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659469", "endSection": "sections.0" }, { "offsetInBeginSection": 498, "offsetInEndSection": 647, "text": "miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659469", "endSection": "sections.0" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1526, "text": "The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659469", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 31, "text": "Role of miR-132 in angiogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659469", "endSection": "title" }, { "offsetInBeginSection": 459, "offsetInEndSection": 818, "text": "The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315408", "endSection": "sections.0" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1740, "text": "Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315408", "endSection": "sections.0" }, { "offsetInBeginSection": 768, "offsetInEndSection": 1630, "text": "Analysis of miRNA expression profiles from sporadic progressive supranuclear palsy (PSP) patients, a major 4R-tau tauopathy, showed that miR-132 is specifically down-regulated in disease. We demonstrate that miR-132 directly targets the neuronal splicing factor polypyrimidine tract-binding protein 2 (PTBP2), which protein levels were increased in PSP patients. miR-132 overexpression or PTBP2 knockdown similarly affected endogenous 4R:3R-tau ratios in neuronal cells. Finally, we provide evidence that miR-132 is inversely correlated with PTBP2 during post-natal brain development at the time when 4R-tau becomes expressed. Taken together, these results suggest that changes in the miR-132/PTBP2 pathway could contribute to the abnormal splicing of tau exon 10 in the brain, and sheds light into the potential role played by miRNAs in a subset of tauopathies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21807765", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "endSection": "sections.0" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1302, "text": "Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "endSection": "sections.0" }, { "offsetInBeginSection": 103, "offsetInEndSection": 236, "text": "Osteosarcoma is the first primary malignant bone tumor, characterized by a complex genetic and resistance to conventional treatments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949564", "endSection": "sections.0" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1306, "text": "Osteosarcoma of rat and human origins showed a miRNA signature, which could discriminate good from bad responders. In particular, we identified five discriminating miRNAs (miR-92a, miR-99b, miR-132, miR-193a-5p and miR-422a) in patient tumors, which could be easily transferable to diagnosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949564", "endSection": "sections.0" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1576, "text": "Levels of several microRNA (miR-10a, -10b, -212, -132, -495) were significantly altered. One of them (miR-132) has been reported to be highly inducible by growth factors and to be a key regulator of neurite outgrowth. Moreover, miR-132-recognition sequences were detected in the mRNA transcripts of two differentially expressed proteins. MicroRNA may thus represent novel biomarkers for neuronal malfunction and potential therapeutic targets for human neurodegenerative diseases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21136867", "endSection": "sections.0" }, { "offsetInBeginSection": 407, "offsetInEndSection": 889, "text": "The data indicate that micro-RNAs encoding miR-9, miR-124a, miR-125b, miR-128, miR-132 and miR-219 are abundantly represented in fetal hippocampus, are differentially regulated in aged brain, and an alteration in specific micro-RNA complexity occurs in Alzheimer hippocampus. These data are consistent with the idea that altered micro-RNA-mediated processing of messenger RNA populations may contribute to atypical mRNA abundance and neural dysfunction in Alzheimer's disease brain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17314675", "endSection": "sections.0" } ] }, { "body": "Which are the human glutamate transporters?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23313319", "http://www.ncbi.nlm.nih.gov/pubmed/25196144", "http://www.ncbi.nlm.nih.gov/pubmed/14730707", "http://www.ncbi.nlm.nih.gov/pubmed/23943043", "http://www.ncbi.nlm.nih.gov/pubmed/9011758", "http://www.ncbi.nlm.nih.gov/pubmed/23393130", "http://www.ncbi.nlm.nih.gov/pubmed/18096700", "http://www.ncbi.nlm.nih.gov/pubmed/15265858", "http://www.ncbi.nlm.nih.gov/pubmed/22539860", "http://www.ncbi.nlm.nih.gov/pubmed/15863236", "http://www.ncbi.nlm.nih.gov/pubmed/26099588", "http://www.ncbi.nlm.nih.gov/pubmed/17311293", "http://www.ncbi.nlm.nih.gov/pubmed/14662797", "http://www.ncbi.nlm.nih.gov/pubmed/14672993", "http://www.ncbi.nlm.nih.gov/pubmed/19074430", "http://www.ncbi.nlm.nih.gov/pubmed/11031254", "http://www.ncbi.nlm.nih.gov/pubmed/9614067", "http://www.ncbi.nlm.nih.gov/pubmed/22427946" ], "ideal_answer": [ "Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined. Using immunofluorescence and postembedding immunogold labeling, we investigated the distributions of the glutamate-aspartate transporter (GLAST or excitatory amino acid transporter 1), vesicular glutamate transporter (VGLUT1), and the AMPA receptor glutamate receptor 4 (GluR4) along the spiral.", "To date, five distinct mammalian glutamate transporters have been cloned. The extracellular levels of excitatory amino acids are kept low by the action of the glutamate transporters. Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined. Expression of short interfering RNA-mediated knockdown of RTN2B decreases the EAAC1 protein level in neurons." ], "exact_answer": [ [ "EAAC1", "EAAT3" ], [ "GLT-1", "glutamate transporter-1", "excitatory amino acid transporter 1" ], [ "GLAST", "Glutamate/aspartate transporter" ], [ "GluR4", "AMPA receptor glutamate receptor 4" ], [ "VGLUT1", "vesicular glutamate transporter" ] ], "type": "list", "id": "57169b63cb4ef8864c00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22539860", "endSection": "title" }, { "offsetInBeginSection": 109, "offsetInEndSection": 470, "text": "Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22539860", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 953, "text": "Using immunofluorescence and postembedding immunogold labeling, we investigated the distributions of the glutamate-aspartate transporter (GLAST or excitatory amino acid transporter 1), vesicular glutamate transporter (VGLUT1), and the AMPA receptor glutamate receptor 4 (GluR4) along the spiral. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14672993", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1710, "text": "Immunogold labeling for GluR4 was confined to synaptic sites, represented by puncta in immunofluorescence. The relative numbers of puncta changed with a gradient similar to that of GLAST labeling. VGLUT1 labeling occurred in IHCs but showed no clear cochleotopic gradient. These data suggest that both the density of innervation and the activity levels of glutamatergic synapses may be involved in modulating regional expression of GLAST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14672993", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 449, "text": "In brain, EAAC1 (excitatory amino acid carrier 1) is the primary neuronal glutamate transporter, localized on the perisynaptic membranes that are near release sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18096700", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Reticulon RTN2B regulates trafficking and function of neuronal glutamate transporter EAAC1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18096700", "endSection": "title" }, { "offsetInBeginSection": 624, "offsetInEndSection": 747, "text": "Previously, we identified an EAAC1-associated protein, GTRAP3-18, an ER protein that prevents ER exit of EAAC1 when induced", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18096700", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 899, "text": "Here we show that RTN2B, a member of the reticulon protein family that mainly localizes in the ER and ER exit sites interacts with EAAC1 and GTRAP3-18", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18096700", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 355, "text": "In this study, uptake of L-[14C]cystine by three of the high affinity sodium-dependent mammalian glutamate transporters (GLT1, GLAST and EAAC1) individually expressed in HEK cells has been determined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15863236", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 942, "text": "Reduction of L-[14C]cystine to L-[14C]cysteine in the presence of 1mM cysteinylglycine increases the uptake rate in HEK(GLT1), HEK(GLAST) and HEK(EAAC1) cells, but only a small proportion (<10%) of L-[14C]cysteine uptake in HEK(GLT1) and HEK(GLAST) cells occurs by the high affinity glutamate transporters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15863236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Position of the third Na+ site in the aspartate transporter GltPh and the human glutamate transporter, EAAT1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427946", "endSection": "title" }, { "offsetInBeginSection": 502, "offsetInEndSection": 701, "text": "We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Glutamate receptors and transporters, including T1R1 and T1R3 (taste receptor 1, subtypes 1 and 3), mGluRs (metabotropic glutamate receptors), EAAC-1 (excitatory amino acid carrier-1), GLAST-1 (glutamate-aspartate transporter-1), and GLT-1 (glutamate transporter-1), are expressed in the gastrointestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23943043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "The ASCTs (alanine, serine, and cysteine transporters) belong to the solute carrier family 1 (SLC1), which also includes the human glutamate transporters (excitatory amino acid transporters, EAATs) and the prokaryotic aspartate transporter GltPh", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393130", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 533, "text": "As astrocytes protect neurons by taking up glutamate via plasma-membrane transporters, we also studied the effect of GRK2 on the localization of the GLutamate ASpartate Transporter (GLAST)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23313319", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1383, "text": "GLT-1, Glutamate Transporter 1, same as excitatory amino acid transporter 2; Glu, glutamate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25196144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Multiple Functions of Glutamate Uptake via Meningococcal GltT-GltM l-Glutamate ABC Transporter in Neisseria meningitidis Internalization into Human Brain Microvascular Endothelial Cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26099588", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 386, "text": "Despite the high degree of amino acid sequence identity between family members, ASCTs function quite differently from the EAATs and GltPh. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393130", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 643, "text": "First, Li(+) cannot support transport by EAAT2, whereas it can support transport by the other excitatory amino acid transporters, and second, EAAT2 is sensitive to a wider range of blockers than other subtypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074430", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 320, "text": "hGLT-1 and hGLuT-1 mRNAs were most abundantly expressed in the brain, while hEAAC1 mRNA expression (3.8 kb and 2,4 kb) was strongest in peripheral organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9011758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Identification of functional domains of the human glutamate transporters EAAT1 and EAAT2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9614067", "endSection": "title" }, { "offsetInBeginSection": 350, "offsetInEndSection": 432, "text": "The glutamate transporter EAAT2 is different from other subtypes in two respects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "DNA methylation dependent silencing of the human glutamate transporter EAAT2 gene in glial cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17311293", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "We have investigated the functional impact of a naturally occurring mutation of the human glutamate transporter GLT1 (EAAT2), which had been detected in a patient with sporadic amyotrophic lateral sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11031254", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 813, "text": "We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP. Using blue native polyacrylamide gel electrophoresis, analysis of concatenated transporters, and chemical cross-linking, we demonstrated that human and prokaryotic glutamate transporters expressed in Xenopus laevis oocytes or in mammalian cells are assembled as trimers composed of three identical subunits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265858", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 431, "text": "Five glutamate transporters in the human brain (EAAT1-5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: human glial restricted precursors (HGRP), human astrocyte precursors (HAPC), and early-differentiated astrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14730707", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 505, "text": "They are known to be multimers; however, the number of subunits forming a functional transporter is controversial. We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265858", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 505, "text": "We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Position of the third Na+ site in the aspartate transporter GltPh and the human glutamate transporter, EAAT1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427946", "endSection": "title" }, { "offsetInBeginSection": 374, "offsetInEndSection": 551, "text": "Immunofluorescent analysis was used to investigate the existence and location of glutamate, glutamate receptor (NR2B), and glutamate transporter (GLT1) in mouse and human sperm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14662797", "endSection": "abstract" } ] }, { "body": "What are the functions of sorting nexin 27?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18690037", "http://www.ncbi.nlm.nih.gov/pubmed/22411990", "http://www.ncbi.nlm.nih.gov/pubmed/23536889", "http://www.ncbi.nlm.nih.gov/pubmed/21303929", "http://www.ncbi.nlm.nih.gov/pubmed/17577583", "http://www.ncbi.nlm.nih.gov/pubmed/15466885", "http://www.ncbi.nlm.nih.gov/pubmed/21300787", "http://www.ncbi.nlm.nih.gov/pubmed/20733053", "http://www.ncbi.nlm.nih.gov/pubmed/17644068", "http://www.ncbi.nlm.nih.gov/pubmed/17828261", "http://www.ncbi.nlm.nih.gov/pubmed/21602791", "http://www.ncbi.nlm.nih.gov/pubmed/17351151", "http://www.ncbi.nlm.nih.gov/pubmed/21926430", "http://www.ncbi.nlm.nih.gov/pubmed/23524343" ], "ideal_answer": [ "Sorting nexin 27 (SNX27) regulates endocytic sorting/recycling and intracellular trafficking of ion channels and receptors." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058305", "http://www.uniprot.org/uniprot/SNX27_HUMAN" ], "type": "summary", "id": "5162da97298dcd4e51000048", "snippets": [ { "offsetInBeginSection": 808, "offsetInEndSection": 1027, "text": "Knockdown of SNX27 by siRNA in HEK293 cells raised MRP4 expression on the plasma membrane, increased the extrusion of 6-[(14)C]mercaptopurine, an MRP4 substrate, and conferred resistance against 6-[(14)C]mercaptopurine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22411990", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Sorting nexin 27 (SNX27) is a 62-kDa protein localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21926430", "endSection": "sections.0" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1315, "text": "Finally, migration assays revealed that depletion of SNX27 from HeLa and mouse principal kidney cortical collecting duct cells significantly decreases cell motility. We propose a model by which SNX27 regulates trafficking of \u03b2-Pix to focal adhesions and thereby influences cell motility.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21926430", "endSection": "sections.0" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1306, "text": "We found that SNX27a redirected part of 5-HT4(a)R to early endosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15466885", "endSection": "sections.0" }, { "offsetInBeginSection": 688, "offsetInEndSection": 800, "text": "sorting nexin 27 (SNX27), a recently described member of a protein family involved in intracellular trafficking,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17351151", "endSection": "sections.0" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1323, "text": "SNX27 co-localized with transferrin receptor-positive vesicles, pointing to its participation in T cell endocytic recycling.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17351151", "endSection": "sections.0" }, { "offsetInBeginSection": 631, "offsetInEndSection": 783, "text": "This protein is a unique member of the sorting nexin family of proteins, a group generally involved in the endocytic and intracellular sorting machinery", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17577583", "endSection": "sections.0" }, { "offsetInBeginSection": 815, "offsetInEndSection": 954, "text": "These previously unreported results indicate that SNX27 is a participant in NK cell polarization, as a mediator or target of the mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644068", "endSection": "sections.0" }, { "offsetInBeginSection": 271, "offsetInEndSection": 480, "text": "Like most sorting nexins, SNX27 possesses a functional PX domain that selectively binds the membrane phospholipid phosphatidylinositol-3-phosphate (PI3P) and is important for trafficking to the early endosome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17828261", "endSection": "sections.0" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1130, "text": "This is consistent with a role of SNX27 as a general regulator for sorting of membrane proteins containing a PDZ-binding motif, and its absence may alter the trafficking of these proteins, leading to growth and survival defects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300787", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Sorting nexin 27 (SNX27) belongs to the sorting nexin family of proteins, which participate in vesicular and protein trafficking. Similarly to all sorting nexin proteins, SNX27 has a functional PX domain that is important for endosome binding, but it is the only sorting nexin with a PDZ domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303929", "endSection": "sections.0" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1424, "text": "These results identify SNX27 as a PDZ-containing component of the T cell immunological synapse, and demonstrate a role for this protein in the regulation of the Ras-ERK pathway, suggesting a functional relationship between SNX27 and DGK\u03b6.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303929", "endSection": "sections.0" }, { "offsetInBeginSection": 406, "offsetInEndSection": 500, "text": "Sorting nexins have been implicated in trafficking of proteins through endosomal compartments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18690037", "endSection": "sections.0" } ] }, { "body": "Do orphan and gene related CpG islands follow power-law-like distributions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25242375" ], "ideal_answer": [ "Yes. Orphan and gene related CpG Islands follow power-law-like distributions in several genomes. The observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899" ], "type": "yesno", "id": "56bb154aac7ad10019000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Orphan and gene related CpG Islands follow power-law-like distributions in several genomes: evidence of function-related and taxonomy-related modes of distribution.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "title" }, { "offsetInBeginSection": 477, "offsetInEndSection": 778, "text": "Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1703, "text": " Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1394, "offsetInEndSection": 1608, "text": "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1695, "offsetInEndSection": 1996, "text": "The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1402, "text": "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1703, "text": "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 779, "text": "Initially, they were assigned the role of transcriptional regulation of protein-coding genes, especially the house-keeping ones, while more recently there is found evidence that they are involved in several other functions as well, which might include regulation of the expression of RNA genes, DNA replication etc. Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1401, "text": "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1402, "offsetInEndSection": 1703, "text": "The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1412, "text": "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract" } ] }, { "body": "What is the proportion of non canonical splice sites in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11125105", "http://www.ncbi.nlm.nih.gov/pubmed/11058137" ], "ideal_answer": [ "Between 1% and 2% of human splice sites do not contain the canonical GT-AG dinucleotides" ], "exact_answer": [ "Between 1% and 2% " ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004274", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019154" ], "type": "factoid", "id": "535d35779a4572de6f000005", "snippets": [ { "offsetInBeginSection": 428, "offsetInEndSection": 635, "text": "Of these, 98.71% contain canonical GT-AG junctions (22 199 entries) and 0.56% have non-canonical GC-AG splice site pairs. The remainder (0.73%) occurs in a lot of small groups (with a maximum size of 0.05%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11125105", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 396, "text": "Of these, 98.71% contain canonical dinucleotides GT and AG for donor and acceptor sites, respectively; 0.56% hold non-canonical GC-AG splice site pairs; and the remaining 0.73% occurs in a lot of small groups (with a maximum size of 0.05%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11058137", "endSection": "abstract" } ] }, { "body": "List protein gel staining methods visualizing the entire protein set.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24043422", "http://www.ncbi.nlm.nih.gov/pubmed/23941326", "http://www.ncbi.nlm.nih.gov/pubmed/24114871", "http://www.ncbi.nlm.nih.gov/pubmed/22665294", "http://www.ncbi.nlm.nih.gov/pubmed/22821490", "http://www.ncbi.nlm.nih.gov/pubmed/23681577", "http://www.ncbi.nlm.nih.gov/pubmed/23256673", "http://www.ncbi.nlm.nih.gov/pubmed/23428344", "http://www.ncbi.nlm.nih.gov/pubmed/23161123", "http://www.ncbi.nlm.nih.gov/pubmed/23977684", "http://www.ncbi.nlm.nih.gov/pubmed/24136520" ], "ideal_answer": [ "Several staining protocols for the visualization of proteins separated by SDS-PAGE have been described in literature: \nfluorescence\nSypro Ruby\nColloidal Coomassie Blue\nCoomassie Blue\nSilver staining\nCoomassie Brilliant Blue" ], "exact_answer": [ [ "fluorochromes", "fluorescence" ], [ "Sypro Ruby" ], [ "Colloidal Coomassie Blue" ], [ "Coomassie Blue" ], [ "Silver staining" ], [ "Coomassie Brilliant Blue" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013194", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016622", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004396", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005782" ], "type": "list", "id": "55184d46622b194345000001", "snippets": [ { "offsetInBeginSection": 707, "offsetInEndSection": 803, "text": "DIGE requires the labelling of proteins by fluorochromes prior to their separation on 2DE gels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136520", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 91, "text": "Stains-All (ISA) staining method for phosphoproteins in SDS-PAGE was described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114871", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 353, "text": " Pro-Q Diamond stain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Quantitative proteome analyses suggest that the well-established stain colloidal Coomassie Blue, when used as an infrared dye, may provide sensitive, post-electrophoretic in-gel protein detection that can rival even Sypro Ruby.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24043422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Several new fast staining protocols for the visualization of proteins separated by SDS-PAGE utilizing Coomassie Blue staining (CBS) have been described in literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23977684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The CyDye family of fluorescent dyes is currently the overwhelming choice for applications in proteomic analysis, using two-dimensional difference gel electrophoresis (2D-DIGE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23941326", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 945, "text": "his enables the co-detection of phosphoproteins as well as total proteins from the same gel and is accomplished by utilizing two different fluorescent stains, the ProQ-Diamond, which stains only phosphorylated proteins, and Sypro Ruby, which stains the entire subset of proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681577", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 449, "text": "Detection of the resulting protein maps relies on staining (i.e. colloidal coomassie blue (CCB) or SYPRO Ruby (SR), in addition to many others). Fluorescent in-gel protein stains are generally preferred for higher sensitivity, reduced background, and wider dynamic range.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23428344", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 486, "text": "Commonly used staining methods with excellent mass spectrometry compatibility are coomassie brilliant blue (CBB) or fluorescent dyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23256673", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "The typical concentration of protein loaded varies from 0.13 to 1.40 \u03bcg/\u03bcL for a classical silver staining method in 2DE gel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Silver staining is widely used to detect protein in polyacrylamide gels when high sensitivity is required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Silver staining is used to detect proteins after electrophoretic separation on polyacrylamide gels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665294", "endSection": "abstract" } ] }, { "body": "What clinical use aptamers may have?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18708826", "http://www.ncbi.nlm.nih.gov/pubmed/23738000", "http://www.ncbi.nlm.nih.gov/pubmed/20855639", "http://www.ncbi.nlm.nih.gov/pubmed/16631118", "http://www.ncbi.nlm.nih.gov/pubmed/9704089", "http://www.ncbi.nlm.nih.gov/pubmed/15968382", "http://www.ncbi.nlm.nih.gov/pubmed/20161621", "http://www.ncbi.nlm.nih.gov/pubmed/21838685", "http://www.ncbi.nlm.nih.gov/pubmed/24198064", "http://www.ncbi.nlm.nih.gov/pubmed/15461575", "http://www.ncbi.nlm.nih.gov/pubmed/18025536", "http://www.ncbi.nlm.nih.gov/pubmed/16842232", "http://www.ncbi.nlm.nih.gov/pubmed/22352726", "http://www.ncbi.nlm.nih.gov/pubmed/20463739", "http://www.ncbi.nlm.nih.gov/pubmed/15926872", "http://www.ncbi.nlm.nih.gov/pubmed/17951900", "http://www.ncbi.nlm.nih.gov/pubmed/12828856" ], "ideal_answer": [ "In the clinic, aptamers may be used to enhance the antigenicity of disseminated tumors, leading to their immune recognition and rejection; to target HPV16 E7 oncoprotein, inhibiting cell proliferation and activating apoptosis of infected cells; to act as inhibitors for targets such as VEGF, in age-related macular degeneration, and thrombin, or von Willebrand factor, in patients with acute coronary syndromes; to target the RNase H domain of the HIV-1 reverse transcriptase and inhibit viral replication; to transfect and activate B cells in human chronic lymphocytic leukemia (CLL); or finally, to be used as probes in CD4-cell phenotyping." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052157", "http://www.biosemantics.org/jochem#4265428", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052158" ], "type": "summary", "id": "5318a6b2b166e2b80600001f", "snippets": [ { "offsetInBeginSection": 1215, "offsetInEndSection": 1642, "text": "In murine tumor models, the aptamer-targeted siRNA-mediated NMD inhibition in tumor cells led to significant inhibition of tumor growth, which was superior to best-in-class \"conventional\" cancer vaccination protocols. Tumor-targeted NMD inhibition forms the basis of a simple, broadly useful, and clinically feasible approach to enhance the antigenicity of disseminated tumors leading to their immune recognition and rejection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198064", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 876, "text": "This study is focused on one aptamer (termed A2). Transfection of this molecule into HPV16-transformed cells resulted in inhibition of cell proliferation (shown using real-time cell electronic sensing and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin V/propidium iodide staining).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738000", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1579, "text": "Transfection of cells with A2 was correlated with the loss of E7 and the induction of apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738000", "endSection": "abstract" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1768, "text": "Aptamers specific for a number of cellular and viral proteins have been documented previously; one aptamer (Macugen) is approved for clinical use and several others are in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738000", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 355, "text": "The high binding affinity and specificity of aptamers allows for isolation of an artificial ligand for theoretically any therapeutic target of interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22352726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "Aptamers are a special class of nucleic acid molecules that are beginning to be investigated for clinical use. These small RNA/DNA molecules can form secondary and tertiary structures capable of specifically binding proteins or other cellular targets; they are essentially a chemical equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small in size, and non-immunogenic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838685", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 741, "text": "In the last two decades, many aptamers have been clinically developed as inhibitors for targets such as vascular endothelial growth factor (VEGF) and thrombin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838685", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 933, "text": "The first aptamer based therapeutic was FDA approved in 2004 for the treatment of age-related macular degeneration and several other aptamers are currently being evaluated in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838685", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1295, "text": "Preclinical studies using aptamer-siRNA chimeras and aptamer targeted nanoparticle therapeutics have been very successful in mouse models of cancer and HIV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838685", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1437, "text": "In summary aptamers are in several stages of development, from pre-clinical studies to clinical trials and even as FDA approved therapeutics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838685", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1233, "text": "In subcutaneous and metastatic tumour models, tumour-targeted delivery of NMD factor-specific siRNAs conjugated to oligonucleotide aptamer ligands led to significant inhibition of tumour growth that was superior to that of vaccination with granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing irradiated tumour cells, and could be further enhanced by co-stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20463739", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 764, "text": "An assortment of non-viral carriers including liposomes, peptides, polymers, and aptamers are being evaluated for their ability to shepherd siRNA to the target tissue and cross the plasma membrane barrier into the cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20161621", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 951, "text": "In addition, a new thromboxane receptor antagonist, NCX-4016, a newly discovered protease-activated receptor antagonist that targets thrombin-induced platelet aggregation, and anti-von Willebrand factor aptamers show tremendous promise in refining antiplatelet therapy by targeting different receptors and molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18708826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025536", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 268, "text": "ARC1779 is a therapeutic aptamer antagonist of the A1 domain of von Willebrand Factor (vWF), the ligand for receptor glycoprotein 1b on platelets. ARC1779 is being developed as a novel antithrombotic agent for use in patients with acute coronary syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025536", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1794, "text": "This is the first-in-human evaluation of a novel aptamer antagonist of vWF. ARC1779 produced dose- and concentration-dependent inhibition of vWF activity and platelet function with duration of effect suitable for the intended clinical use in acute coronary syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Wet age-related macular degeneration and diabetic retinopathy are pathological consequences of vascular endothelial growth factor (VEGF) release as a reaction to deficiency of oxygen and nutrients in the macular cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17951900", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 848, "text": "FDA recently approved two drugs specifically aimed at VEGF, bevacizumab, a humanized monoclonal antibody, and pegaptinib, a pegylated aptamer with application in ophthalmic pathologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16842232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Delivery of double-stranded DNA thioaptamers into HIV-1 infected cells for antiviral activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16631118", "endSection": "title" }, { "offsetInBeginSection": 401, "offsetInEndSection": 550, "text": "Our lead thioaptamer, R12-2, targets the RNase H domain of the HIV-1 reverse transcriptase (RT) and inhibits viral infection in U373-MAGI-CCR5 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16631118", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1263, "text": "In this report, we demonstrate that monothioate-modified DNA duplex oligonucleotides can be efficiently delivered into cells by liposome-based transfection agents to inhibit HIV replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16631118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Nucleic acid aptamers in therapeutic anticoagulation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15968382", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Pegaptanib sodium for the treatment of neovascular age-related macular degeneration", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15926872", "endSection": "title" }, { "offsetInBeginSection": 617, "offsetInEndSection": 722, "text": "Pegaptanib sodium is one of the first therapeutics belonging to the class of compounds known as aptamers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15926872", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1075, "text": "The article highlights and summarises the results of the multi-centre, randomised, sham-controlled clinical trials with pegaptanib sodium to treat subfoveal choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15926872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Regulatable aptamers in medicine: focus on antithrombotic strategies", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15461575", "endSection": "title" }, { "offsetInBeginSection": 397, "offsetInEndSection": 692, "text": "After a decade of intensive research, technology development and initial clinical evaluation, aptamers have now demonstrated broad potential as direct protein ligands and inhibitors, and thus represent an exciting class of compounds for the development of new therapeutic and diagnostic agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15461575", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 840, "text": "Two R-aptamers (R10-60 and D-R15-8) with the predominant shared characteristics were selected for further study on primary human chronic lymphocytic leukemia (CLL) B cells, which are well known to be difficult to transfect and activate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12828856", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1633, "text": "Together, these findings suggest that the sequence compositions in R-aptamers that promote multimerization and contain optimal ISS CpG motifs facilitate the delivery of ISS-ODN to CLL cells and enhance the activation of these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12828856", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 528, "text": "In particular, the use of aptamers for the alleviation of blood clotting and the treatment of AIDS are considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9704089", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 674, "text": "We synthesized an RNA aptamer probe specific for human CD4 using a reported sequence and investigated the potential use of this probe in cell phenotyping. Studies in cultured cells demonstrated that the synthetic CD4 aptamer had a nearly identical cell-binding specificity as the standard CD4 antibody. Fluorescent microscopy confirmed that the aptamer and antibody generated the same CD4 staining pattern in cells without competing with one another.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20855639", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1291, "text": "transfection of HPV16-transformed cells with A2 appeared to result in the loss of E7 and rise in pRb levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738000", "endSection": "abstract" } ] }, { "body": "What is the causative agent of the \"Panama disease\" affecting bananas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24304681", "http://www.ncbi.nlm.nih.gov/pubmed/18943184", "http://www.ncbi.nlm.nih.gov/pubmed/12926878", "http://www.ncbi.nlm.nih.gov/pubmed/25969777", "http://www.ncbi.nlm.nih.gov/pubmed/9482835", "http://www.ncbi.nlm.nih.gov/pubmed/24376590", "http://www.ncbi.nlm.nih.gov/pubmed/23355016" ], "triples": [ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "true" }, { "p": "http://purl.uniprot.org/core/otherName", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "fungal sp. ZZF51" }, { "p": "http://purl.uniprot.org/core/commonName", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "Panama disease fungus" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "Fusarium oxysporum" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "FUSOX" }, { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/taxonomy/660034", "o": "http://purl.uniprot.org/taxonomy/5507" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/660034", "o": "Fusarium oxysporum II5" }, { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/taxonomy/909454", "o": "http://purl.uniprot.org/taxonomy/5507" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/909454", "o": "Fusarium oxysporum Cotton" }, { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/taxonomy/660031", "o": "http://purl.uniprot.org/taxonomy/5507" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/660031", "o": "Fusarium oxysporum PHW808" }, { "p": "http://purl.uniprot.org/core/strain", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "http://linkedlifedata.com/resource/#_2503" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://linkedlifedata.com/resource/#_2503", "o": "FOM24" } ], "ideal_answer": [ "Panama disease of banana is caused by the fungus Fusarium oxysporum f. sp. cubense." ], "exact_answer": [ "Fusarium oxysporum f. sp. cubense" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010176", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010935" ], "type": "factoid", "id": "56b7083376d8bf8d13000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Fusarium oxysporum f. sp. cubense (Foc), the causal agent of Fusarium wilt (Panama disease), is one of the most devastating diseases of banana (Musa spp.)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24376590", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 322, "text": "avendish, the most widely grown banana cultivar, is relatively resistant to Race 1 of Fusarium oxysporum f. sp. cubense (Foc1) which caused widespread Panama disease during the first half of the 20th century but is susceptible to Tropical Race 4 of Foc (Foc TR4) which is threatening world banana production. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304681", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 454, "text": "Fusarium oxysporum f. sp. cubense race 4 (FOC), the causal agent of Panama disease in banana,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23355016", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 213, "text": "Fusarium oxysporum f.sp. cubense, a causative agent of Panama disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969777", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 110, "text": "Fusarium wilt of banana (also known as Panama disease) is caused by Fusarium oxysporum f. sp. cubense", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18943184", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 323, "text": " inoculated with Fusarium oxysporum f.sp. cubense (FOC), Race 4, the causal agent of Panama disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12926878", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 76, "text": "the fungus causing Panama disease of banana", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9482835", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Panama disease of banana, caused by the fungus Fusarium oxysporum f. sp. cubense, is a serious constraint both to the commercial production of banana and cultivation for subsistence agriculture", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9482835", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Nalmefene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22078567", "http://www.ncbi.nlm.nih.gov/pubmed/21651459", "http://www.ncbi.nlm.nih.gov/pubmed/21291870" ], "ideal_answer": [ "Nalmefene shows opioid receptor antagonism, binds the \u03bc-opioid receptor (MOR1) and modulates opioidergic transmission in the CNS." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.biosemantics.org/jochem#4258016", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040542" ], "type": "summary", "id": "52bf1df903868f1b06000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 908, "text": "Opioids that stimulate the \u03bc-opioid receptor (MOR1) are the most frequently prescribed and effective analgesics. Here we present a structural model of MOR1. Molecular dynamics simulations show a ligand-dependent increase in the conformational flexibility of the third intracellular loop that couples with the G protein complex. These simulations likewise identified residues that form frequent contacts with ligands. We validated the binding residues using site-directed mutagenesis coupled with radioligand binding and functional assays. The model was used to blindly screen a library of \u223c1.2 million compounds. From the 34 compounds predicted to be strong binders, the top three candidates were examined using biochemical assays. One compound showed high efficacy and potency. Post hoc testing revealed this compound to be nalmefene, a potent clinically used antagonist, thus further validating the model. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22078567", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 332, "text": "The neurobiological mechanism by which opioid modulators affect drinking behavior is based on the strong connection between the endogenous opioid system, the dopamine system and the influence of the CNS stress response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21651459", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1085, "text": "Naltrexone- and to a lesser extent nalmefene- is an agent that modulates opioidergic transmission in the CNS and it shows a limited but well-studied efficacy in treating alcohol dependence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21651459", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 578, "text": "Several derivatives of Naltrexone, Nalmefene (Nal) and JKB-119, exert immunomodulatory activity; however, unlike Nal, JKB-119 does not show significant opioid receptor antagonism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21291870", "endSection": "abstract" } ] }, { "body": "Synostosis of which cranial structures are characteristic to the Mercedes Benz syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20048621", "http://www.ncbi.nlm.nih.gov/pubmed/19396832", "http://www.ncbi.nlm.nih.gov/pubmed/9780908" ], "ideal_answer": [ "Synostosis of sagittal and lambdoid structures are characteristic to the Mercedes Benz syndrome." ], "exact_answer": [ [ "sagittal" ], [ "lambdoid" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11971", "http://www.disease-ontology.org/api/metadata/DOID:2340", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "list", "id": "54cf43abf693c3b16b000008", "snippets": [ { "offsetInBeginSection": 172, "offsetInEndSection": 295, "text": "Among these are a trisutural fusion, dubbed the \"Mercedes Benz pattern,\" involving the sagittal and both lambdoid sutures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048621", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1615, "text": "CONCLUSIONS: Despite fusion of the sagittal suture, the surgical treatment for Mercedes Benz pattern craniosynostosis should include skull lengthening, not reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 414, "text": "Multisutural craniosynostosis that includes bilateral lambdoid and sagittal synostosis (BLSS) results in a very characteristic head shape with frontal bossing, turribrachycephaly, biparietal narrowing, occipital concavity, and inferior displacement of the ears. This entity has been reported both in the genetics literature as craniofacial dyssynostosis and in the surgical literature as \"Mercedes Benz\" syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19396832", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 72, "text": "Bilambdoid and posterior sagittal synostosis: the Mercedes Benz syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9780908", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "A consistent pattern of craniosynostosis in the sagittal and bilateral lambdoid sutures is described in three patients. The external cranial ridging associated with fusion of these sutures produces a characteristic triradiate, or \"Mercedes Benz,\" appearance to the posterior skull.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9780908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Bilambdoid and posterior sagittal synostosis: the Mercedes Benz syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9780908", "endSection": "title" } ] }, { "body": "Can valproic acid act as an activator of AMPK?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24105977", "http://www.ncbi.nlm.nih.gov/pubmed/23889921" ], "ideal_answer": [ "Yes, valproic acid canact as an activator of AMPK.", "VPA is a novel activator of AMP-activated protein kinase (AMPK)" ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031588", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055372", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004679", "http://www.uniprot.org/uniprot/AAKB1_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000479", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014635", "http://www.biosemantics.org/jochem#4271063", "http://www.uniprot.org/uniprot/AAPK2_HUMAN" ], "type": "yesno", "id": "52f89ee42059c6d71c00004d", "snippets": [ { "offsetInBeginSection": 89, "offsetInEndSection": 261, "text": "Here we demonstrate that VPA is a novel activator of AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism, using primary mouse and human hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105977", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1503, "text": "These studies are the first to establish VPA and its metabolites as in vitro activators of AMPK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105977", "endSection": "abstract" } ] }, { "body": "Which signaling pathways have been associated with medulloblastoma formation and growth?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21679342", "http://www.ncbi.nlm.nih.gov/pubmed/20232424", "http://www.ncbi.nlm.nih.gov/pubmed/16510586", "http://www.ncbi.nlm.nih.gov/pubmed/24982684", "http://www.ncbi.nlm.nih.gov/pubmed/18651559", "http://www.ncbi.nlm.nih.gov/pubmed/9973222", "http://www.ncbi.nlm.nih.gov/pubmed/19738049", "http://www.ncbi.nlm.nih.gov/pubmed/16707597", "http://www.ncbi.nlm.nih.gov/pubmed/20053726", "http://www.ncbi.nlm.nih.gov/pubmed/25052069", "http://www.ncbi.nlm.nih.gov/pubmed/17545597", "http://www.ncbi.nlm.nih.gov/pubmed/21358093", "http://www.ncbi.nlm.nih.gov/pubmed/16398471", "http://www.ncbi.nlm.nih.gov/pubmed/19747111", "http://www.ncbi.nlm.nih.gov/pubmed/15013214", "http://www.ncbi.nlm.nih.gov/pubmed/15195141" ], "ideal_answer": [ "Medulloblastoma comprises approximately 20% of all primary pediatric brain tumors. Multiple signaling pathways have been associated with disease formation and growth. These include the developmental pathways Hedgehog, Notch, and Wnt, as well as pathways in which the receptor tyrosine kinases (RTK) c-Met, erbB2, IGF-R and TrkC, and the oncoprotein Myc are involved." ], "exact_answer": [ [ "Hedgehog" ], [ "Notch" ], [ "Wnt" ], [ "c-Met" ], [ "erbB2" ], [ "IGF-R" ], [ "TrkC" ], [ "Myc" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009966", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015398", "http://www.disease-ontology.org/api/metadata/DOID:3858" ], "type": "list", "id": "55391ce8bc4f83e828000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Hedgehog (Hh) signaling is an important factor in growth and patterning during embryonic development. A mutation in Patched, Smoothened or Gli1, which regulate the Hh signaling pathway, might lead to the onset of glioblastoma, basal cell carcinoma, medulloblastoma and rhabdomyosarcoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679342", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1546, "text": "These data indicate that inhibition of Aurora Kinase A inhibits cell growth in medulloblastoma through inhibition of pro-proliferative signaling pathways Wnt, Myc, and RB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20232424", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 324, "text": "Multiple signaling pathways have been associated with medulloblastoma formation and growth. These include the developmental pathways Hedgehog, (Hh) Notch, and Wnt as well as the receptor tyrosine kinases (RTK) c-Met, erbB2, IGF-R and TrkC, and the oncoprotein Myc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18651559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973222", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973222", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 961, "text": "Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome by inhibiting tumor growth through the promotion of apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "During development, proliferation of cerebellar granule neuron precursors (CGNP), candidate cells-of-origin for the pediatric brain tumor medulloblastoma, requires signaling by Sonic hedgehog (Shh) and insulin-like growth factor (IGF), the pathways of which are also implicated in medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19738049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15195141", "endSection": "title" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1077, "text": "Ectopic expression of alpha and beta interferons in the developing brain also induces Shh-mediated medulloblastoma formation, suggesting a possible role for antiviral response in the genesis of medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16398471", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 922, "text": "Aberrant activation of the Hedgehog (Hh) and Wnt developmental pathways is associated with medulloblastoma, but deregulation of other molecular pathways, including insulin-like growth factor (IGF) signaling, has also been implicated in the pathogenesis of the tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19747111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Sunitinib induces apoptosis and growth arrest of medulloblastoma tumor cells by inhibiting STAT3 and AKT signaling pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20053726", "endSection": "title" }, { "offsetInBeginSection": 282, "offsetInEndSection": 418, "text": "Aberrant activation of the Sonic hedgehog (Shh) and insulin-like growth factor (IGF) pathways is associated with human medulloblastomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16510586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "N-myc can substitute for insulin-like growth factor signaling in a mouse model of sonic hedgehog-induced medulloblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16510586", "endSection": "title" }, { "offsetInBeginSection": 655, "offsetInEndSection": 920, "text": "Aberrant activation of the Hedgehog (Hh) and Wnt developmental pathways is associated with medulloblastoma, but deregulation of other molecular pathways, including insulin-like growth factor (IGF) signaling, has also been implicated in the pathogenesis of the tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19747111", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 486, "text": "Aberrant expression/activation of EGFR is found in multiple human cancers, including medulloblastoma, the most prevalent pediatric brain cancer, and often has been associated with metastasis, poor prognosis, and resistance to chemotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25052069", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 560, "text": "We emphasize the cancer-relevance of cilia-dependent signaling pathways and proteins including mTOR, VHL, TSC, WNT, Aurora-A, NEDD9, and Hedgehog, and highlight the emerging role of ciliary dysfunction in renal cell carcinoma, medulloblastoma, and breast cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24982684", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1125, "text": "Here, we show that in medulloblastoma cells, both EGF and ouabain activate Erk1/2 and PI3K/Akt signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25052069", "endSection": "abstract" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1856, "text": "Expression level of tumor/metastasis suppressive miRNAs in the WNT signaling associated medulloblastomas is likely to determine their response to treatment, and thus, these miRNAs would be important biomarkers for risk stratification within the WNT signaling associated medulloblastomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358093", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 417, "text": "Aberrant activation of the Sonic hedgehog (Shh) and insulin-like growth factor (IGF) pathways is associated with human medulloblastomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16510586", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 474, "text": "Shh-dependent medulloblastoma formation is enhanced by hyperactive insulin-like growth factor (IGF) signaling and ectopic expression of Myc oncogenes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Phosphatidylinositol 3'-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16707597", "endSection": "title" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1319, "text": "A number of miRNAs like miR-193a, miR-224/miR-452 cluster, miR-182/miR-183/miR-96 cluster, and miR-148a having potential tumor/metastasis suppressive activity were found to be overexpressed in the WNT signaling associated medulloblastomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358093", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1189, "text": "The requirement for SHH-Gli signaling in the growth of the mouse brain, together with the ability of inappropriate pathway activation in the cerebellum to cause medulloblastomas, and the inhibition of the growth of a number of brain tumors with cyclopamine, a SHH signaling inhibitor, underscores the critical role of the SHH-GLI pathway in brain growth and tumor formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15013214", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 921, "text": "Aberrant activation of the Hedgehog (Hh) and Wnt developmental pathways is associated with medulloblastoma, but deregulation of other molecular pathways, including insulin-like growth factor (IGF) signaling, has also been implicated in the pathogenesis of the tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19747111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358093", "endSection": "title" } ] }, { "body": "What is the role of invadopodia in EMT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23873099", "http://www.ncbi.nlm.nih.gov/pubmed/24086398", "http://www.ncbi.nlm.nih.gov/pubmed/21725138", "http://www.ncbi.nlm.nih.gov/pubmed/19169796", "http://www.ncbi.nlm.nih.gov/pubmed/21397860", "http://www.ncbi.nlm.nih.gov/pubmed/22529104", "http://www.ncbi.nlm.nih.gov/pubmed/19656240", "http://www.ncbi.nlm.nih.gov/pubmed/23991004" ], "ideal_answer": [ "In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. An important type of such membrane protrusions are the invadopodia, which have been increasingly recognized as important drivers of local invasion in metastasis. They are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058750", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837" ], "type": "summary", "id": "5319ac7fb166e2b806000033", "snippets": [ { "offsetInBeginSection": 574, "offsetInEndSection": 651, "text": "FHOD1, a poorly studied formin, appeared to be markedly upregulated upon EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086398", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1475, "text": "Furthermore, functional assays demonstrated that FHOD1 contributes to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our results indicate that FHOD1 participates in cytoskeletal changes in EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086398", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 230, "text": "Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM) by using matrix metalloproteinases (MMPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23991004", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 674, "text": "Previously, we isolated a highly invasive A431-III subline from parental A431 cells by Boyden chamber assay. The A431-III cells possess higher invasive and migratory abilities, elevated levels of MMP-9 and an enhanced epithelial-mesenchymal transition (EMT) phenotype. In this study, we discovered that A431-III cells had an increased potential to form invadopodia and an improved capacity to degrade ECM compared with the original A431 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23991004", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 744, "text": "Activated Twist upregulates N-cadherin and downregulates E-cadherin, which are the hallmarks of EMT. Moreover, Twist plays an important role in some physiological processes involved in metastasis, like angiogenesis, invadopodia, extravasation, and chromosomal instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23873099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Transforming growth factor \u03b2 (TGF-\u03b2)-stimulated epithelial-mesenchymal transition (EMT) is an important developmental process that has also been implicated in increased cell invasion and metastatic potential of cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22529104", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 566, "text": "Herein, we demonstrate that TGF-\u03b2-induced Hic-5 up-regulation or ectopic expression of Hic-5 in normal MCF10A cells promoted increased extracellular matrix degradation and invasion through the formation of invadopodia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22529104", "endSection": "abstract" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1127, "text": "These data identify Hic-5 as a critical mediator of TGF-\u03b2-stimulated invadopodia formation, cell migration, and invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22529104", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 638, "text": "Recently, invadopodia have been increasingly recognized as important drivers of local invasion in metastasis. Invadopodia are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix. We recently found that the transcription factor Twist1, a central regulator of the epithelial-mesenchymal transition (EMT), promotes invadopodia formation via upregulation of platelet-derived growth factor receptor (PDGFR) expression and activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21725138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Twist1-induced invadopodia formation promotes tumor metastasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21397860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "The Twist1 transcription factor is known to promote tumor metastasis and induce Epithelial-Mesenchymal Transition (EMT). Here, we report that Twist1 is capable of promoting the formation of invadopodia, specialized membrane protrusions for extracellular matrix degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21397860", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 493, "text": "Twist1 induces PDGFR\u03b1 expression, which in turn activates Src, to promote invadopodia formation. We show that Twist1 and PDGFR\u03b1 are central mediators of invadopodia formation in response to various EMT-inducing signals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21397860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Podosome-like structures of non-invasive carcinoma cells are replaced in epithelial-mesenchymal transition by actin comet-embedded invadopodia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656240", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Podosomes and invadopodia are actin-based structures at the ventral cell membrane, which have a role in cell adhesion, migration and invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656240", "endSection": "abstract" }, { "offsetInBeginSection": 1758, "offsetInEndSection": 2136, "text": "In conclusion, EMT affects the invasion machinery of oral squamous carcinoma cells. Non-invasive squamous carcinoma cells constitutively organize podosomes, whereas invasive cells form invadopodia. The club-ended cell extensions, or externalized invadopodia, are involved in ECM degradation and maintenance of contact to adhesion substrate and surrounding cells during invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656240", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 819, "text": "In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169796", "endSection": "abstract" } ] }, { "body": "What are cancer driver genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23416983", "http://www.ncbi.nlm.nih.gov/pubmed/19574499", "http://www.ncbi.nlm.nih.gov/pubmed/24009526", "http://www.ncbi.nlm.nih.gov/pubmed/24233780", "http://www.ncbi.nlm.nih.gov/pubmed/20707908", "http://www.ncbi.nlm.nih.gov/pubmed/22851646", "http://www.ncbi.nlm.nih.gov/pubmed/21169372", "http://www.ncbi.nlm.nih.gov/pubmed/24084849", "http://www.ncbi.nlm.nih.gov/pubmed/24214964", "http://www.ncbi.nlm.nih.gov/pubmed/23694700", "http://www.ncbi.nlm.nih.gov/pubmed/18339846", "http://www.ncbi.nlm.nih.gov/pubmed/19081671" ], "ideal_answer": [ "Recent sequencing and resequencing (i.e., polymorphism identification) efforts have catalyzed the quest for 'driver' mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to 'passenger' mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation. Analysis of the frequency of specific mutations across different tumors has been able to identify some, but not all of the mutated genes that contribute to tumor initiation and progression. A subset of these mutations contribute to tumor progression (known as \"driver\" mutations) whereas the majority of these mutations are effectively neutral (known as \"passenger\" mutations)." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052138" ], "type": "summary", "id": "534428feaeec6fbd0700000a", "snippets": [ { "offsetInBeginSection": 225, "offsetInEndSection": 493, "text": "We constructed DriverDB (http://ngs.ym.edu.tw/driverdb/), a database which incorporates 6079 cases of exome-seq data, annotation databases (such as dbSNP, 1000 Genome and Cosmic) and published bioinformatics algorithms dedicated to driver gene/mutation identification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "DriverDB: an exome sequencing database for cancer driver gene identification.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214964", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "With the ability to fully sequence tumor genomes/exomes, the quest for cancer driver genes can now be undertaken in an unbiased manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24084849", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 452, "text": "Here we show that the combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24084849", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 964, "text": "In summary, the catalog of driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24084849", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 270, "text": "A subset of these mutations contribute to tumor progression (known as \"driver\" mutations) whereas the majority of these mutations are effectively neutral (known as \"passenger\" mutations)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18339846", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 421, "text": "The ability to differentiate between drivers and passengers will be critical to the success of upcoming large-scale cancer DNA resequencing projects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18339846", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 1263, "text": " In fact, recent sequencing and resequencing (i.e., polymorphism identification) efforts have catalyzed the quest for protein kinase 'driver' mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to kinase 'passenger' mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19081671", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1213, "text": "This method was applied to available breast cancer, colorectal cancer, and glioblastoma sequence data, and identified Wnt/TGF-beta cross-talk, Wnt/VEGF signaling, and MAPK/focal adhesion kinase pathways as targets of rare driver mutations in breast, colorectal cancer, and glioblastoma, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19574499", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 314, "text": "Analysis of the frequency of specific mutations across different tumors has been able to identify some, but not all of the mutated genes that contribute to tumor initiation and progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19574499", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 251, "text": "We are developing a cross-species comparison strategy to distinguish between cancer driver- and passenger gene alteration candidates, by utilizing the difference in genomic location of orthologous genes between the human and other mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20707908", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 161, "text": "Major tumor sequencing projects have been conducted in the past few years to identify genes that contain 'driver' somatic mutations in tumor samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169372", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1115, "text": "At the same time, we determined that some genes previously reported as drivers were not significant by the new analysis because mutations in these genes occurred mainly in tumors with large background mutation rates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22851646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Herein we report a proof-of-principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver-passenger distinction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23416983", "endSection": "abstract" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1818, "text": "Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23416983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Adjusting for background mutation frequency biases improves the identification of cancer driver genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23694700", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The identification of cancer drivers is a major goal of current cancer research", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24009526", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1265, "text": "We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24009526", "endSection": "abstract" } ] }, { "body": "What is a mitochondrial nucleoid?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23637282", "http://www.ncbi.nlm.nih.gov/pubmed/19703654", "http://www.ncbi.nlm.nih.gov/pubmed/23721879", "http://www.ncbi.nlm.nih.gov/pubmed/20577028", "http://www.ncbi.nlm.nih.gov/pubmed/19704786", "http://www.ncbi.nlm.nih.gov/pubmed/23220174", "http://www.ncbi.nlm.nih.gov/pubmed/15126284" ], "ideal_answer": [ "A naked mtDNA molecule is longer than a typical mitochondrion and is therefore compacted in vivo to form a nucleoprotein complex, denoted the mitochondrial nucleoid." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042645", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090144", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009295", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024101", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090143" ], "type": "summary", "id": "552016a36b348bb82c000018", "snippets": [ { "offsetInBeginSection": 208, "offsetInEndSection": 373, "text": "A naked mtDNA molecule is longer than a typical mitochondrion and is therefore compacted in vivo to form a nucleoprotein complex, denoted the mitochondrial nucleoid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23721879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The packaging of mitochondrial DNA (mtDNA) into DNA-protein assemblies called nucleoids provides an efficient segregating unit of mtDNA,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23637282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Mitochondrial DNA (mtDNA) is organized in nucleoids in complex with accessory proteins, proteins of mtDNA replication and gene expression machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23220174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The independent mitochondrial genetic information is organized in so-called mitochondrial nucleoids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20577028", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 179, "text": " packaging of mitochondrial DNA (mtDNA) into protein-DNA assemblies called nucleoids confers higher-order organization to the mitochondrial genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704786", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 420, "text": "mitochondrial DNA is packaged into macromolecular assemblies called nucleoids, composed of one or more copies of mitochondrial DNA and associated proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19703654", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 178, "text": "human mitochondrial DNA (mtDNA) had long been believed to be rather naked because mitochondria lack histone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15126284", "endSection": "abstract" } ] }, { "body": "What is the treatment of amiodarone-induced thyrotoxicosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22130792", "http://www.ncbi.nlm.nih.gov/pubmed/19109209", "http://www.ncbi.nlm.nih.gov/pubmed/20583541", "http://www.ncbi.nlm.nih.gov/pubmed/19105148", "http://www.ncbi.nlm.nih.gov/pubmed/22386340", "http://www.ncbi.nlm.nih.gov/pubmed/19675515", "http://www.ncbi.nlm.nih.gov/pubmed/18410546", "http://www.ncbi.nlm.nih.gov/pubmed/21865355", "http://www.ncbi.nlm.nih.gov/pubmed/22865896", "http://www.ncbi.nlm.nih.gov/pubmed/21225109", "http://www.ncbi.nlm.nih.gov/pubmed/18595575", "http://www.ncbi.nlm.nih.gov/pubmed/18421194", "http://www.ncbi.nlm.nih.gov/pubmed/19622616" ], "ideal_answer": [ "Treatment of amiodarone-induced thyrotoxicosis is complex and may include drugs such as antithyroid drugs, beta-blockers, corticosteroids lithium as well as iopanoic acid in preparation of thyroidectomy. Total thyroidectomy and radioiodine represent alternative treatment options" ], "type": "summary", "id": "518cb513310faafe08000007", "snippets": [ { "offsetInBeginSection": 1746, "offsetInEndSection": 1902, "text": "Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22130792", "endSection": "sections.0" }, { "offsetInBeginSection": 1924, "offsetInEndSection": 2085, "text": "Total thyroidectomy, by rapidly restoring euthyroidism, may improve cardiac function and reduce the risk of mortality in AIT patients with severe LV dysfunction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22865896", "endSection": "sections.0" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1957, "text": "Prednisone restores euthyroidism in most type 2 AIT patients, irrespective of amiodarone continuation or withdrawal. However, continuing amiodarone increases the recurrence rate of thyrotoxicosis, causing a delay in the stable restoration of euthyroidism and a longer exposure of the heart to thyroid hormone excess.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865355", "endSection": "sections.0" }, { "offsetInBeginSection": 714, "offsetInEndSection": 912, "text": "Steroid therapy should be started when findings indicate type II or mixed-type AIT. Beta blockers may prevent heart thyrotoxicosis and recurrence of primary arrhythmia if amiodarone is discontinued.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20583541", "endSection": "sections.0" }, { "offsetInBeginSection": 1668, "offsetInEndSection": 1793, "text": "Glucocorticoids are the first-line treatment in type 2 AIT, whereas thionamides play no role in this destructive thyroiditis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622616", "endSection": "sections.0" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1065, "text": "iopanoic can be used to rapidly lower FT(3) levels and to treat symptoms of thyrotoxicosis in a preoperative setting.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19105148", "endSection": "sections.0" }, { "offsetInBeginSection": 633, "offsetInEndSection": 752, "text": "The patient responded to iopanoic acid with a rapid decrease in his FT(3) level and slight increase in his FT(4) level.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19105148", "endSection": "sections.0" }, { "offsetInBeginSection": 1791, "offsetInEndSection": 1890, "text": "In patients with type-2 AIT, RAI treatment may be the therapy of choice for thyroid gland ablation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18595575", "endSection": "sections.0" }, { "offsetInBeginSection": 1582, "offsetInEndSection": 1687, "text": "In type 1 AIT thionamides represent the treatment of choice for North Americans as well as for Europeans,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410546", "endSection": "sections.0" }, { "offsetInBeginSection": 1876, "offsetInEndSection": 2008, "text": "Glucocorticoids are the selected treatment for type 2 AIT, alone (62%vs. 46% in Europe, P < 0.05) or in association with thionamides", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410546", "endSection": "sections.0" }, { "offsetInBeginSection": 2041, "offsetInEndSection": 2200, "text": "After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 AIT less frequently by North Americans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410546", "endSection": "sections.0" } ] }, { "body": "How does exercise affect thyroid hormone receptors expression in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "http://www.ncbi.nlm.nih.gov/pubmed/21625820" ], "ideal_answer": [ "Exercise has been shown to increase TR\u03b21 receptor expression in young rats. Exercise has been shown to increase both TR\u03b11 and TR\u03b21 receptor expression in aged rats." ], "concepts": [ "http://www.uniprot.org/uniprot/THAB_PAROL", "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THAB_XENLA", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/TR150_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/TR150_HUMAN", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://www.uniprot.org/uniprot/TR150_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0030375", "http://www.uniprot.org/uniprot/THBB_XENLA", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "summary", "id": "5159cc88d24251bc050000a4", "snippets": [ { "offsetInBeginSection": 1107, "offsetInEndSection": 1162, "text": "Exercise increased the TR\u03b21 receptor, L-channel and NCX", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21625820", "endSection": "sections.0" }, { "offsetInBeginSection": 878, "offsetInEndSection": 1093, "text": "Expression of TR-alpha1 and TR-beta1 proteins in the heart were significantly lower in sedentary aged rats than in sedentary young rats and were significantly higher in trained aged rats than in sedentary aged rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "endSection": "sections.0" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1040, "text": "Myocyte TRbeta1 was upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine, T3), in culture and exercise in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "endSection": "sections.0" } ] }, { "body": "Is the Drosophila Translational Control Element (TCE) involved in spermatogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22984601", "http://www.ncbi.nlm.nih.gov/pubmed/8111973" ], "ideal_answer": [ "Yes. The Drosophila Translational Control Element (TCE), a 12 nucleotide long sequence element, was demonstrated to be necessary for translational control of expression in the male germ line of Drosophila melanogaster." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330", "http://amigo.geneontology.org/amigo/term/GO:0007283", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013091", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029721" ], "type": "yesno", "id": "56b8841189239fd259000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Gene regulation in Drosophila spermatogenesis: analysis of protein binding at the translational control element TCE.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8111973", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "We have previously identified a 12 nucleotide long sequence element, the TCE, that was demonstrated to be necessary for translational control of expression in the male germ line of Drosophila melanogaster (Sch\u00e4fer et al., 1990).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8111973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Gene regulation in Drosophila spermatogenesis: analysis of protein binding at the translational control element TCE", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8111973", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22984601", "endSection": "title" }, { "offsetInBeginSection": 188, "offsetInEndSection": 389, "text": "Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22984601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22984601", "endSection": "title" } ] }, { "body": "What are the symptoms of abacavir hypersensitivity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12719670", "http://www.ncbi.nlm.nih.gov/pubmed/12869229", "http://www.ncbi.nlm.nih.gov/pubmed/18855539", "http://www.ncbi.nlm.nih.gov/pubmed/17245797" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/class", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1297", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseaseClass/Immunological" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A12061804", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1840547", "o": "http://linkedlifedata.com/resource/umls/label/A12061804" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A11948761", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11994170", "o": "ABACAVIR HYPERSENSITIVITY, SUSCEPTIBILITY TO" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17030126", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A7589770", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A7589770" } ], "ideal_answer": [ "Patients receiving abacavir develop an idiosyncratic hypersensitivity reaction that can include a wide range of symptoms. The most common are: fever, enathema, skin rash, nausea, vomiting, diarrhoea, cough, gastrointestinal disorders, anaphylactic shock, respiratory symptoms." ], "exact_answer": [ [ "fever" ], [ "enathema" ], [ "skin rash" ], [ "nausea" ], [ "vomiting" ], [ "diarrhea" ], [ "cough" ], [ "gastrointestinal disorders" ], [ "anaphylactic shock" ], [ "respiratory symptoms" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4239946", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006967", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002524", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.biosemantics.org/jochem#4274474", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004342", "http://www.biosemantics.org/jochem#4274473" ], "type": "list", "id": "51542dc3d24251bc0500007e", "snippets": [ { "offsetInBeginSection": 148, "offsetInEndSection": 286, "text": "patients receiving abacavir develop a hypersensitivity reaction, characterized by rash, fever and, occasionally, multisystemic involvement", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18855539", "endSection": "sections.0" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1127, "text": "The predictors included any one of several specific symptoms commonly found with this reaction, a claims diagnosis of adverse effect of drug, anaphylactic shock or unspecified allergy, and a discontinuation in abacavir prior to completing a 90-day course of therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17245797", "endSection": "sections.0" }, { "offsetInBeginSection": 176, "offsetInEndSection": 615, "text": "patients who receive abacavir develop an idiosyncratic hypersensitivity reaction. The most common symptoms are fever, skin rash and gastrointestinal disorders. Respiratory symptoms occurred in approximately 20% of patients who have hypersensitivity reaction. We describe the first case, to our knowledge, of hypesensitivity reaction characterized by enanthema and fever without skin rash promptly resolved after discontinuation of abacavir", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12719670", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 161, "text": "Abacavir is associated with an infrequent but potentially serious hypersensitivity reaction (HSR) that can include a wide range of signs and symptoms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17245797", "endSection": "sections.0" }, { "offsetInBeginSection": 229, "offsetInEndSection": 515, "text": "Rash was associated with hypersensitivity (odds ratio [OR] = 13.1, P = 0.02) as was the presence of nausea (OR = 30, P < 0.001), vomiting (OR = 17.1, P = 0.001) or diarrhoea (OR = 22, P < 0.001). The number of gastrointestinal symptoms was also predictive of hypersensitivity reaction (", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12869229", "endSection": "sections.0" }, { "offsetInBeginSection": 747, "offsetInEndSection": 957, "text": "the number of gastrointestinal symptoms (OR = 8.6, P = 0.0032), cough (OR = 0.039, P = 0.02) and rash (OR = 16.9, P = 0.07). Abacavir hypersensitivity is strongly associated with gastrointestinal (GI) symptoms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12869229", "endSection": "sections.0" } ] }, { "body": "What is the effect of ivabradine in heart failure with preserved ejection fraction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22833515", "http://www.ncbi.nlm.nih.gov/pubmed/20005474", "http://www.ncbi.nlm.nih.gov/pubmed/23916925", "http://www.ncbi.nlm.nih.gov/pubmed/23274284", "http://www.ncbi.nlm.nih.gov/pubmed/21212673" ], "ideal_answer": [ "I(f)-channel inhibition potentially exhibits beneficial effects in diastolic heart failure. In patients with heart failure with preserved ejection fraction (HFpEF), short-term treatment with ivabradine increased exercise capacity, with a contribution from improved left ventricular filling pressure response to exercise as reflected by the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity. Ivabradine has demonstrated benefits in HFpEF without improving mortality.\tIn db/db, a model of HFpEF, ivabradine improved vascular stiffness, left ventricular contractility, and diastolic function. Furthermore, ivabradine reduces cardiac fibrosis in hypercholesterolemic rabbits." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054144", "http://www.biosemantics.org/jochem#4266225" ], "type": "summary", "id": "532f0511d6d3ac6a34000024", "snippets": [ { "offsetInBeginSection": 864, "offsetInEndSection": 1094, "text": "Traditional agents with strong evidence in HFrEF have proved unsuccessful in HFpEF. Newer agents such as angiotensin receptor neprilysin inhibitor, sildenafil, and ivabradine have demonstrated benefits without improving mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23274284", "endSection": "abstract" }, { "offsetInBeginSection": 1664, "offsetInEndSection": 1893, "text": "In db/db, a model of HFPEF, selective HR reduction by If-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, If-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22833515", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1359, "text": "Selective HR reduction with IVA reduces DD and cardiac fibrosis in hypercholesterolemic rabbits. These beneficial effects of IVA support testing pure HR reduction in patients with diastolic heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21212673", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 839, "text": "Beside its use in therapy of coronary artery disease, I(f)-channel inhibition potentially exhibits beneficial effects in systolic and diastolic heart failure as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20005474", "endSection": "abstract" }, { "offsetInBeginSection": 1781, "offsetInEndSection": 2079, "text": "In patients with HFpEF, short-term treatment with ivabradine increased exercise capacity, with a contribution from improved left ventricular filling pressure response to exercise as reflected by the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23916925", "endSection": "abstract" } ] }, { "body": "Is low T3 syndrome a prognostic marker in patients with renal insufficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/958900", "http://www.ncbi.nlm.nih.gov/pubmed/21189433", "http://www.ncbi.nlm.nih.gov/pubmed/22419237", "http://www.ncbi.nlm.nih.gov/pubmed/18211669", "http://www.ncbi.nlm.nih.gov/pubmed/17908160", "http://www.ncbi.nlm.nih.gov/pubmed/999108", "http://www.ncbi.nlm.nih.gov/pubmed/7385804", "http://www.ncbi.nlm.nih.gov/pubmed/19367004", "http://www.ncbi.nlm.nih.gov/pubmed/21389695", "http://www.ncbi.nlm.nih.gov/pubmed/20178724", "http://www.ncbi.nlm.nih.gov/pubmed/16230785", "http://www.ncbi.nlm.nih.gov/pubmed/23857979", "http://www.ncbi.nlm.nih.gov/pubmed/17082213", "http://www.ncbi.nlm.nih.gov/pubmed/16775599", "http://www.ncbi.nlm.nih.gov/pubmed/22260378", "http://www.ncbi.nlm.nih.gov/pubmed/22881233" ], "ideal_answer": [ "Low fT3 is an independent predictor of death in chronic kidney disease, in particular in dialised patients at end-stage renal diseases." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058186", "http://www.disease-ontology.org/api/metadata/DOID:784", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051437", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051436" ], "type": "yesno", "id": "5325de7d9b2d7acc7e000029", "snippets": [ { "offsetInBeginSection": 561, "offsetInEndSection": 723, "text": "Low T3 was particularly common (44.3 %), and clearly associated with increased 6- and 12-month mortality and decreased overall survival (log rank test, P=0.007). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22881233", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1131, "text": "Increased rT3 may be more common in ESRD patients than previously described, and together with decreased T3 it may serve as an indicator of poor prognosis in subsequent months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22881233", "endSection": "abstract" }, { "offsetInBeginSection": 2451, "offsetInEndSection": 2568, "text": "The presence of TFT alterations seems to not be associated with clinical and prognostic implications in AKI patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419237", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 939, "text": "Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17908160", "endSection": "abstract" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1364, "text": "Finally, low T3 but not low free triiodothyronine was associated with worse all-cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17908160", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1423, "text": " In Cox analyses, fT3 was a significant predictor of mortality independent of the main traditional as well as non-traditional risk factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17082213", "endSection": "abstract" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1774, "text": "All-cause and CV mortality rates were significantly higher in patients with 'lower' T3 levels than in the 'higher' T3 group (113.4 vs 18.2 events per 1000 patient-years, P<0.001, and 49.8 vs 9.1 events per 1000 patient-years, P=0.001, respectively). The Kaplan-Meier analysis also showed significantly worse cumulative survival rates in the 'lower' T3 group (P<0.001). In the Cox regression analysis, low T3 was an independent predictor of all-cause mortality even after adjusting for traditional risk factors (hazard ratio=3.76, P=0.021). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23857979", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1566, "text": "In CKD patients with proteinuria, low T3 concentration predicted all-cause mortality and cardiovascular event independently of the severity of proteinuria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22260378", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1344, "text": "Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21389695", "endSection": "abstract" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1435, "text": "These data suggest that low FT3 levels are not predictive for mortality in a subgroup of stable HD patients who could survive more than 12 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20178724", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1438, "text": "Low fT3 is an independent predictor of death in hemodialysis patients. These data lend support to the hypothesis that thyroid dysfunction is implicated in the high risk of the ESRD population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16775599", "endSection": "abstract" } ] }, { "body": "Does burning mouth syndrome preferentially affect post-mepopausal women?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8725589", "http://www.ncbi.nlm.nih.gov/pubmed/17439072", "http://www.ncbi.nlm.nih.gov/pubmed/15055637", "http://www.ncbi.nlm.nih.gov/pubmed/18985004", "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "http://www.ncbi.nlm.nih.gov/pubmed/12017897", "http://www.ncbi.nlm.nih.gov/pubmed/23772971", "http://www.ncbi.nlm.nih.gov/pubmed/23201368", "http://www.ncbi.nlm.nih.gov/pubmed/15911160", "http://www.ncbi.nlm.nih.gov/pubmed/3476895", "http://www.ncbi.nlm.nih.gov/pubmed/21685517", "http://www.ncbi.nlm.nih.gov/pubmed/21528120", "http://www.ncbi.nlm.nih.gov/pubmed/17967714", "http://www.ncbi.nlm.nih.gov/pubmed/20701667", "http://www.ncbi.nlm.nih.gov/pubmed/20230455", "http://www.ncbi.nlm.nih.gov/pubmed/12907696", "http://www.ncbi.nlm.nih.gov/pubmed/12764983", "http://www.ncbi.nlm.nih.gov/pubmed/19689438", "http://www.ncbi.nlm.nih.gov/pubmed/16142094", "http://www.ncbi.nlm.nih.gov/pubmed/17849966", "http://www.ncbi.nlm.nih.gov/pubmed/20440632", "http://www.ncbi.nlm.nih.gov/pubmed/8469539", "http://www.ncbi.nlm.nih.gov/pubmed/8170453", "http://www.ncbi.nlm.nih.gov/pubmed/7838464", "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "http://www.ncbi.nlm.nih.gov/pubmed/12618668", "http://www.ncbi.nlm.nih.gov/pubmed/19450321", "http://www.ncbi.nlm.nih.gov/pubmed/22612823", "http://www.ncbi.nlm.nih.gov/pubmed/23050296", "http://www.ncbi.nlm.nih.gov/pubmed/24096230", "http://www.ncbi.nlm.nih.gov/pubmed/17452954", "http://www.ncbi.nlm.nih.gov/pubmed/17541900", "http://www.ncbi.nlm.nih.gov/pubmed/9237148", "http://www.ncbi.nlm.nih.gov/pubmed/15024358", "http://www.ncbi.nlm.nih.gov/pubmed/11441716", "http://www.ncbi.nlm.nih.gov/pubmed/21903545", "http://www.ncbi.nlm.nih.gov/pubmed/20597947", "http://www.ncbi.nlm.nih.gov/pubmed/9844361", "http://www.ncbi.nlm.nih.gov/pubmed/18305436", "http://www.ncbi.nlm.nih.gov/pubmed/21418666", "http://www.ncbi.nlm.nih.gov/pubmed/10478959", "http://www.ncbi.nlm.nih.gov/pubmed/11603307", "http://www.ncbi.nlm.nih.gov/pubmed/19658340", "http://www.ncbi.nlm.nih.gov/pubmed/6589575", "http://www.ncbi.nlm.nih.gov/pubmed/16905808", "http://www.ncbi.nlm.nih.gov/pubmed/18558051", "http://www.ncbi.nlm.nih.gov/pubmed/15195716", "http://www.ncbi.nlm.nih.gov/pubmed/18625105", "http://www.ncbi.nlm.nih.gov/pubmed/23787507", "http://www.ncbi.nlm.nih.gov/pubmed/10446526", "http://www.ncbi.nlm.nih.gov/pubmed/16637799", "http://www.ncbi.nlm.nih.gov/pubmed/7629360", "http://www.ncbi.nlm.nih.gov/pubmed/2700889", "http://www.ncbi.nlm.nih.gov/pubmed/20038880", "http://www.ncbi.nlm.nih.gov/pubmed/22030140", "http://www.ncbi.nlm.nih.gov/pubmed/18278306" ], "ideal_answer": [ "BMS is observed principally in middle-aged patients and postmenopausal women \nBMS mostly affects elderly citizens, especially postmenopausal women with prevalence up to 12-18%." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002054", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002056", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008593", "http://www.disease-ontology.org/api/metadata/DOID:403", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016387", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014930", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017698", "http://www.disease-ontology.org/api/metadata/DOID:4331" ], "type": "yesno", "id": "531d76a2267d7dd05300000a", "snippets": [ { "offsetInBeginSection": 172, "offsetInEndSection": 303, "text": "It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096230", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 304, "text": "It occurs more commonly in middle-aged and elderly women and often affects the tongue tip and lateral borders, lips, and hard and soft palate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23772971", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 289, "text": "BMS is a chronic disorder that frequently affects women and is characterised by burning symptoms of the oral mucosa without clinical signs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22612823", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 279, "text": "It mostly affects elderly citizens, especially postmenopausal women with prevalence up to 12-18%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22030140", "endSection": "abstract" } ] }, { "body": "Which biomarker is widely used in the diagnosis of Ewing sarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12783138" ], "ideal_answer": [ "CD99 is a hallmark marker for Ewing sarcoma and primitive neuroectodermal tumors." ], "exact_answer": [ "CD99" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.disease-ontology.org/api/metadata/DOID:4980", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512", "http://www.disease-ontology.org/api/metadata/DOID:3368" ], "type": "factoid", "id": "55376663bc4f83e82800000a", "snippets": [ { "offsetInBeginSection": 218, "offsetInEndSection": 463, "text": "half of B-LBL patients are negative for CD45 (leucocyte common antigen, LCA), a widely used marker for the diagnosis of lymphoma, and a significant portion express CD99, a marker for Ewing's sarcoma (ES) or primitive neuroectodermal tumor (PNET)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783138", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 463, "text": "Moreover, half of B-LBL patients are negative for CD45 (leucocyte common antigen, LCA), a widely used marker for the diagnosis of lymphoma, and a significant portion express CD99, a marker for Ewing's sarcoma (ES) or primitive neuroectodermal tumor (PNET)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783138", "endSection": "abstract" } ] }, { "body": "Proteomic analyses have revealed proteins associated with the triple-negative breast cancers. List some proposed proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19416831", "http://www.ncbi.nlm.nih.gov/pubmed/23172894", "http://www.ncbi.nlm.nih.gov/pubmed/22414580", "http://www.ncbi.nlm.nih.gov/pubmed/20068102", "http://www.ncbi.nlm.nih.gov/pubmed/21630460", "http://www.ncbi.nlm.nih.gov/pubmed/19485423", "http://www.ncbi.nlm.nih.gov/pubmed/23436753", "http://www.ncbi.nlm.nih.gov/pubmed/22178447", "http://www.ncbi.nlm.nih.gov/pubmed/22934887", "http://www.ncbi.nlm.nih.gov/pubmed/22692575", "http://www.ncbi.nlm.nih.gov/pubmed/20005186" ], "ideal_answer": [ "Selected proteins of interest proposed from triple-negative cancer proteomic studies are CD44, PARP1, Mage-A4, LSR, RAB25, S100A14, MUC1, Hsp90, Actin, 14-3-3, vimentin, HSP70, CK18, moesin, IDH2, CRABP2, SEC14L2, beta-catenin, MUC18, Stat1 and CD74." ], "exact_answer": [ [ "CD44" ], [ "PARP1" ], [ "Mage-A4" ], [ "LSR" ], [ "RAB25" ], [ "S100A14" ], [ "MUC1" ], [ "Hsp90" ], [ "Actin" ], [ "14-3-3" ], [ "vimentin" ], [ "HSP70" ], [ "CK18" ], [ "moesin" ], [ "IDH2" ], [ "CRABP2" ], [ "SEC14L2" ], [ "beta-catenin" ], [ "MUC18" ], [ "Stat1" ], [ "CD74" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.disease-ontology.org/api/metadata/DOID:0060081", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "list", "id": "51595fb0d24251bc0500009c", "snippets": [ { "offsetInBeginSection": 839, "offsetInEndSection": 969, "text": "Some of these proteins are of outstanding interest in the biology and clinical management of this disease, such as CD44 and PARP1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23436753", "endSection": "sections.0" }, { "offsetInBeginSection": 1254, "offsetInEndSection": 1532, "text": "We present here our results, including a large cumulative database of proteins based on the analysis of 78 TNBCs, and the identification and validation of one specific protein, Mage-A4, which was expressed in a significant fraction of TNBC and Her2-positive/ER negative lesions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23172894", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Proteomic profiling of triple-negative breast carcinomas in combination with a three-tier orthogonal technology approach identifies Mage-A4 as potential therapeutic target in estrogen receptor negative breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23172894", "endSection": "title" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1334, "text": "Further, we performed comparative quantitative proteomic and gene array analyses of these cells and identified potential novel markers of breast cancer cells with tumor-initiating features, such as lipolysis-stimulated lipoprotein receptor (LSR), RAB25, S100A14 and mucin 1 (MUC1), as well as a novel 31-gene signature capable of predicting distant metastasis in cohorts of estrogen receptor-negative human breast cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22692575", "endSection": "sections.0" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1718, "text": "he results identify Hsp90 as a critical and multimodal target in this most difficult to treat breast cancer subtype and support the use of the Hsp90 inhibitor PU-H71 for clinical trials involving patients with TNBC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19416831", "endSection": "sections.0" }, { "offsetInBeginSection": 227, "offsetInEndSection": 511, "text": "We obtained differential expression patterns for several glycolytic enzymes (as for example MDH2, PGK1, TKT, Aldolase1), cytokeratins (CK7, 8, 9, 14, 17, 19), further structure proteins (vimentin, fibronectin, L-plastin), for NME1-NME2, lactoferrin, and members of the Annexin family.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19485423", "endSection": "sections.0" }, { "offsetInBeginSection": 1689, "offsetInEndSection": 2085, "text": "he expression of calreticulin, cellular retinoic acid-binding protein II, chloride intracellular channel protein 1, EF-1-beta, galectin 1, peroxiredoxin-2, platelet-derived endothelial cell growth factor, protein disulfide isomerase and ubiquitin carboxyl-terminal hydrolase 5 were further validated using a tissue microarray containing 70 malignant breast carcinomas of various grades of atypia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20005186", "endSection": "sections.0" }, { "offsetInBeginSection": 484, "offsetInEndSection": 554, "text": "The first is characterized by high expression of Stat1, Mx1, and CD74.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22178447", "endSection": "sections.0" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1330, "text": "This effect was accompanied with a marked increase in the membrane expression of beta-catenin, MUC18, plexins, integrins, and other proteins involved in cell adhesion and cancer metastasis. Taken together, our results show that Stat1/CD74 positive triple-negative tumors are more aggressive and suggest an approach for development of better diagnostics and more targeted therapies for triple negative breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22178447", "endSection": "sections.0" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1185, "text": "Proteomic analysis also identified high levels of IDH2 and CRABP2 and low levels of SEC14L2 to be prognostic markers for overall breast cancer survival.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22414580", "endSection": "sections.0" }, { "offsetInBeginSection": 651, "offsetInEndSection": 796, "text": "Proteomic and validation immunohistochemical analyses revealed that alpha-defensins (DEFA) were overexpressed in tumors from patients with a pCR.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20068102", "endSection": "sections.0" }, { "offsetInBeginSection": 583, "offsetInEndSection": 913, "text": "The expression of a selected group of high abundance and/or breast cancer-specific potential biomarkers including thromobospondin 1, galectin-3 binding protein, cathepsin D, vimentin, zinc-\u03b12-glycoprotein, CD44, and EGFR from the breast cancer cell lines and in their culture media were further validated by Western blot analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22934887", "endSection": "sections.0" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1354, "text": "his provided novel evidence for PMA regulation of the enzymes glyceraldehyde-3-phosphate dehydrogenase, nucleolar RNA helicase 2 and Heterogeneous nuclear ribonucleoprotein M.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21630460", "endSection": "sections.0" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1501, "text": "Among them, we identify downregulation of components of the Ras/Raf/MAPK pathway and G(2)-M phase to contribute to its anti-proliferative effect, degradation of activated Akt and Bcl-xL to induce apoptosis, and inhibition of activated NF-kappaB, Akt, ERK2, Tyk2, and PKC to reduce TNBC invasive potential.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19416831", "endSection": "sections.0" } ] }, { "body": "Which signalling pathway is involved in Tuberous Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20457704", "http://www.ncbi.nlm.nih.gov/pubmed/19506736", "http://www.ncbi.nlm.nih.gov/pubmed/12172555", "http://www.ncbi.nlm.nih.gov/pubmed/15388940", "http://www.ncbi.nlm.nih.gov/pubmed/12766776", "http://www.ncbi.nlm.nih.gov/pubmed/12766775", "http://www.ncbi.nlm.nih.gov/pubmed/23159330", "http://www.ncbi.nlm.nih.gov/pubmed/12556239", "http://www.ncbi.nlm.nih.gov/pubmed/15562827", "http://www.ncbi.nlm.nih.gov/pubmed/12711473", "http://www.ncbi.nlm.nih.gov/pubmed/18368626" ], "ideal_answer": [ "Tuberous Sclerosis is a multisystem genetic disorder caused by mutation in TSC1 or TSC2 gene, that leads to hyperactivation of the mTOR signalling pathway, and subsequent dysregulation of cell growth control." ], "exact_answer": [ "Tuberous Sclerosis is caused by hyperactivation of the mTOR signalling pathway." ], "concepts": [ "http://www.uniprot.org/uniprot/TSC2_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://www.uniprot.org/uniprot/TSC1_RAT", "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC2_MOUSE", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC1_MOUSE", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ], "type": "factoid", "id": "52f11b922059c6d71c000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Tuberous sclerosis, caused by germline mutations in the TSC1 or TSC2 genes, is associated with aberrant upregulation of the mammalian target of rapamycin (mTOR) signalling pathway, resulting in growth of tumours, including renal angiomyolipomas (AMLs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20457704", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 581, "text": "Tuberous Sclerosis Complex is genetically determined with an autosomal dominant inheritance and is caused by inactivating mutations in either the TSC1 or TSC2 genes. TSC1/2 genes play a fundamental role in the regulation of phosphoinositide 3-kinase (PI3K) signalling pathway, inhibiting the mammalian target of rapamycin (mTOR) through activation of the GTPase activity of Rheb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19506736", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 541, "text": "TSC is an autosomal dominant disorder caused by mutation in either of two genes: TSC1, encoding hamartin, and TSC2, encoding tuberin. Both proteins form a complex inhibiting mTOR signalling pathway and thus regulate cell size and proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18368626", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 1058, "text": "Recent findings from this laboratory and others suggests that the tumour suppressor complex made of two proteins TSC1/hamartin and TSC2/tuberin, acts as a negative regulator of mTOR/S6K1 signalling. Mutations in either TSC1 or TSC2 are genetically linked to tuberous sclerosis complex (TSC) syndrome, which can lead to severe pathological consequences, including mental retardation, epilepsy and autism, as well as cardiac, pulmonary and renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15562827", "endSection": "abstract" }, { "offsetInBeginSection": 1774, "offsetInEndSection": 1911, "text": "Here we review recent findings demonstrating that the TSC1/TSC2 inhibitory complex normally acts on Rheb to mediate mTOR/S6K1-signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15562827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Ras homologue enriched in brain (Rheb) represents a unique group of small GTPases and shares moderate sequence identity with the Ras/Rap subfamily. It acts downstream of nutrient signalling as the direct target of the tuberous sclerosis complex (TSC) and upstream of mTOR/S6K1/4EBP in the insulin-signalling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15388940", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 300, "text": "Recent studies suggest that the tuberous sclerosis complex Tsc1-Tsc2 may couple insulin signalling to Tor activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12766776", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 656, "text": "Our genetic and biochemical analyses suggest that Rheb functions downstream of the tumour suppressors Tsc1 (tuberous sclerosis 1)-Tsc2 in the TOR (target of rapamycin) signalling pathway to control growth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12766775", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 656, "text": "Our results indicate activation of a mammalian target of rapamycin metabolic pathway in tuberous sclerosis lesions, which contributes to their growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12711473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Tuberous sclerosis (TSC) is an autosomal dominant hamartoma syndrome whose causative genes (TSC1 and TSC2) were identified 5 and 9 years ago respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12556239", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 639, "text": "Recent studies in Drosophila have pinpointed a critical function for the DrosophilaTSC1/TSC2 homologues in the regulation of cell size. Epistasis experiments and a variety of biochemical studies that followed have indicated a critical function for these proteins in the highly conserved PI-3-kinase-Akt-mTOR signalling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12556239", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 576, "text": "Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour suppressors that are responsible for the tuberous sclerosis syndrome, antagonize this amino acid-TOR signalling pathway. We show that Tsc1 and Tsc2 can physically associate with TOR and function upstream of TOR genetically. In Drosophila melanogaster and mammalian cells, loss of Tsc1 and Tsc2 results in a TOR-dependent increase of S6K activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12172555", "endSection": "abstract" } ] }, { "body": "Can life style changes reduce oxidative stress", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21150342", "http://www.ncbi.nlm.nih.gov/pubmed/23185200", "http://www.ncbi.nlm.nih.gov/pubmed/19031760", "http://www.ncbi.nlm.nih.gov/pubmed/23105513" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18450882", "o": "D008019" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18450882", "o": "Life Style Induced Illness" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2936742", "o": "http://linkedlifedata.com/resource/umls/label/A18450882" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18450882", "o": "MeSH" } ], "ideal_answer": [ "Our results suggested that life style changes which related to migration might reduce DNA damage in Hasake nationalities." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008019", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018384" ], "type": "yesno", "id": "52f88a972059c6d71c000033", "snippets": [ { "offsetInBeginSection": 1016, "offsetInEndSection": 1435, "text": "The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185200", "endSection": "abstract" }, { "offsetInBeginSection": 1792, "offsetInEndSection": 1981, "text": "Once detected, these patients may be offered more aggressive treatment strategies such as early pharmacotherapy in addition to life style changes targeted to maintaining pericyte integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150342", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 976, "text": "Our results suggested that life style changes which related to migration might reduce DNA damage in Hasake nationalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19031760", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1268, "text": "Low levels of antioxidants and increased oxidative stress with insulin resistance in metabolic syndrome suggests that besides therapeutic life style changes (TLC) as suggested in ATP III guidelines inclusion of antioxidant vitamins, fruits and vegetable could be beneficial to ward off the consequences of metabolic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23105513", "endSection": "abstract" } ] }, { "body": "Which is the relation between sweating and anaerobic threshold?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2703281", "http://www.ncbi.nlm.nih.gov/pubmed/12937031", "http://www.ncbi.nlm.nih.gov/pubmed/9694410", "http://www.ncbi.nlm.nih.gov/pubmed/7588694" ], "ideal_answer": [ "There is no clear evidence of the relationship between sweating and anaerobic threshold" ], "exact_answer": [ "There is no clear evidence of the relationship between sweating and anaerobic threshold" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015308", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008660", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013546" ], "type": "factoid", "id": "536787467d100faa09000010", "snippets": [ { "offsetInBeginSection": 1353, "offsetInEndSection": 1560, "text": "It is concluded that the sweating response during upright recovery is significantly modified by exercise intensity and may likely be influenced by the nonthermal baroreceptor reflex adjustments postexercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12937031", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 429, "text": " The purpose of this paper is to delineate the effects of training status, heat acclimation, environmental conditions and host factors on the sweating response to exercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9694410", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1399, "text": "These results would suggest that at a given exercise intensity in subjects with a higher aerobic capacity body temperature is maintained with a lower sweating rate than that in subjects with a lower aerobic capacity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7588694", "endSection": "abstract" } ] }, { "body": "Name monoclonal antibody against SLAMF7.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26035255", "http://www.ncbi.nlm.nih.gov/pubmed/25287778", "http://www.ncbi.nlm.nih.gov/pubmed/25312647", "http://www.ncbi.nlm.nih.gov/pubmed/24941981" ], "ideal_answer": [ "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer cell-mediated antibody-dependent cellular cytotoxicity of SLAMF7-expressing myeloma cells." ], "exact_answer": [ "signaling lymphocytic activation molecule-F7" ], "concepts": [ "http://www.uniprot.org/uniprot/SLAF7_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000911" ], "type": "factoid", "id": "56c077e9ef6e394741000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26035255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) of SLAMF7-expressing myeloma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287778", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 275, "text": "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25312647", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 347, "text": "One of the most promising MoAb is elotuzumab, the only humanized IgG1 MoAb specifically targeting CS1 (SLAMF7), a cell surface glycoprotein that is highly expressed in plasma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24941981", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 365, "text": "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25312647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) of SLAMF7-expressing myeloma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": " New agents are awaited for the treatment of multiple myeloma and research is ongoing for the development of monoclonal antibodies (MoAbs) targeting the tumor cells. One of the most promising MoAb is elotuzumab, the only humanized IgG1 MoAb specifically targeting CS1 (SLAMF7), a cell surface glycoprotein that is highly expressed in plasma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24941981", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 276, "text": "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25312647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26035255", "endSection": "abstract" } ] }, { "body": "What is the mode of action of bedaquiline?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24563587", "http://www.ncbi.nlm.nih.gov/pubmed/25203970", "http://www.ncbi.nlm.nih.gov/pubmed/25114537", "http://www.ncbi.nlm.nih.gov/pubmed/24173008", "http://www.ncbi.nlm.nih.gov/pubmed/23459487", "http://www.ncbi.nlm.nih.gov/pubmed/24259600" ], "ideal_answer": [ "Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents that is used for treatment of multi drug resistant tuberculosis." ], "type": "summary", "id": "54d9071a4b1fd0d33c000007", "snippets": [ { "offsetInBeginSection": 122, "offsetInEndSection": 289, "text": "Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents in more than 40 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25203970", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 974, "text": "Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25114537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Bedaquiline - The first ATP synthase inhibitor against multi drug resistant tuberculosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24563587", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 472, "text": " Bedaquiline is an anti-tuberculosis drug with unique mechanism of action. It selectively inhibits the mycobacterial energy metabolism i.e. ATP synthesis and found to be effective against all states of Mycobacterium tuberculosis like active, dormant, replicating, non-replicating, intracellular and extracellular.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24563587", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 927, "text": "DATA SYNTHESIS: Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259600", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 764, "text": "By directly inhibiting adenosine triphosphate (ATP) synthase, bedaquiline is effective against both replicating and dormant mycobacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24173008", "endSection": "abstract" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1396, "text": "Enhanced sterilizing capacity via synergistic depletion of ATP further exhibits the promising potential of bedaquiline with pyrazinamide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24173008", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 850, "text": "Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259600", "endSection": "abstract" } ] }, { "body": "Does helicobacter pylori infection increase risk for ischemic stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18988408", "http://www.ncbi.nlm.nih.gov/pubmed/21060340", "http://www.ncbi.nlm.nih.gov/pubmed/15694938", "http://www.ncbi.nlm.nih.gov/pubmed/18249521", "http://www.ncbi.nlm.nih.gov/pubmed/22713083", "http://www.ncbi.nlm.nih.gov/pubmed/12725602", "http://www.ncbi.nlm.nih.gov/pubmed/19355997", "http://www.ncbi.nlm.nih.gov/pubmed/18665936", "http://www.ncbi.nlm.nih.gov/pubmed/12388919", "http://www.ncbi.nlm.nih.gov/pubmed/11588309", "http://www.ncbi.nlm.nih.gov/pubmed/22688569", "http://www.ncbi.nlm.nih.gov/pubmed/9805426", "http://www.ncbi.nlm.nih.gov/pubmed/11157171", "http://www.ncbi.nlm.nih.gov/pubmed/17669100", "http://www.ncbi.nlm.nih.gov/pubmed/11155465", "http://www.ncbi.nlm.nih.gov/pubmed/16230797", "http://www.ncbi.nlm.nih.gov/pubmed/21775946", "http://www.ncbi.nlm.nih.gov/pubmed/11253332", "http://www.ncbi.nlm.nih.gov/pubmed/18346651", "http://www.ncbi.nlm.nih.gov/pubmed/14500942", "http://www.ncbi.nlm.nih.gov/pubmed/16386288", "http://www.ncbi.nlm.nih.gov/pubmed/16004850", "http://www.ncbi.nlm.nih.gov/pubmed/12063957", "http://www.ncbi.nlm.nih.gov/pubmed/24890556", "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "http://www.ncbi.nlm.nih.gov/pubmed/18706211", "http://www.ncbi.nlm.nih.gov/pubmed/16466297", "http://www.ncbi.nlm.nih.gov/pubmed/15166387", "http://www.ncbi.nlm.nih.gov/pubmed/12147540", "http://www.ncbi.nlm.nih.gov/pubmed/9436737", "http://www.ncbi.nlm.nih.gov/pubmed/11412864" ], "ideal_answer": [ "Findings regarding association between helicobacter pylori infection and ischemic stroke risk are conflicting. There is evidence to suggest that helicobacter pylori infection is associated with increased risk for ischemic stroke and should be considered stroke risk factors. However, some studies reported no association between helicobacter pylori infection and stroke." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016480", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016481" ], "type": "summary", "id": "551c2cd26b348bb82c00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Helicobacter pylori (H. pylori) infection is reported to be associated with many extragastrointestinal manifestations, such as hematological diseases [idiopathic thrombocytopenic purpura (ITP) and unexplained iron deficiency anemia (IDA)], cardiovascular diseases (ischemic heart diseases), neurological disorders (stroke, Parkinson's disease, Alzheimer's disease), obesity and skin disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Helicobacter pylori infection contributes to high risk of ischemic stroke: evidence from a meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22688569", "endSection": "title" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1859, "text": "This meta-analysis indicated that chronic H. pylori infection was significantly associated with an increased risk of IS, especially for non-cardioembolic IS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22688569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "In the last years, a considerable number of studies have been performed on the relationship between infection from Helicobacter Pylori and atherosclerotic diseases, like stroke and ischemic heart disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21775946", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 249, "text": "However, there are conflicting results on the relevance of chronic infection by Helicobacter pylori as a risk factor for ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "endSection": "abstract" }, { "offsetInBeginSection": 2123, "offsetInEndSection": 2266, "text": "CONCLUSIONS: This case-control study does not reveal any strong association between chronic Helicobacter pylori infection and ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1106, "text": "Case-control and prospective studies indicate that chronic infections, such as periodontitis, chronic bronchitis and infection with Helicobacter pylori, Chlamydia pneumoniae or Cytomegalovirus, might increase stroke risk, although considerable variation exists in the results of these studies, and methodological issues regarding serological results remain unresolved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21060340", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1208, "text": "Chronic infections, presently discussed as stroke risk factors mainly include periodontitis and infections with Helicobacter pylori (Hp) and Chlamydia pneumoniae (Cp). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19355997", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 901, "text": "CONCLUSION: H. Pylori gastritis is not independently associated with increased risk for stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18988408", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1495, "text": "CONCLUSIONS: Our results support the hypothesis that CagA-seropositive strains infection is significantly associated with susceptibility to ischemic strokes and coronary heart diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18706211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "BACKGROUND: Previous studies suggested an association between CagA-positive H. pylori strains and ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18665936", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1199, "text": "CONCLUSIONS: Our findings suggest that CagA-positive strains of H. pylori are significantly associated to atherosclerotic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18665936", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1452, "text": "We concluded that H pylori infection is common in DM and seems to be linked to the presence of atherosclerosis and ischemic cerebrovascular stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18346651", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 897, "text": "Interesting results show that H. pylori infection affects atherosclerosis and is weakly associated with ischemic heart disease and stroke. Moreover, CagA-positive H. pylori strains may play a role in the natural history of atherosclerotic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18249521", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 284, "text": "Interestingly, the majority of the extradigestive-related literature is focused on two vascular manifestations: stroke and ischemic heart disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17669100", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 490, "text": "Chronic infectious diseases that may increase the risk of stroke include periodontitis, chronic bronchitis and infections with microbial antigens, such as Helicobacter pylori and Chlamydia pneumoniae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16466297", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1446, "text": "CONCLUSIONS: These results suggest that H. pylori infection is a risk factor for ischemic stroke and that CD14 polymorphism is not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16386288", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1653, "text": " CONCLUSIONS: Our case-control study provides evidence of an association between the immune response to H. pylori , a marker of prior infection with this organism and noncardioembolic ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16230797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Case-control studies and a few prospective studies have indicated that chronic infections may add to the risk of stroke and that acute infections may act as trigger factors for stroke. Such chronic infections include periodontal disease, infection with Chlamydia pneumoniae or Helicobacter pylori, and chronic bronchitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16004850", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1602, "text": "Chronic H. pylori infection still showed an overall association with ischemic stroke (odds ratio for all subtypes combined: 2.57; 95% CI: 1.09-6.08) after adjusting for major cardiovascular risk factors. These results suggest that chronic H. pylori infection may be a triggering factor that increases the risk of acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15694938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15166387", "endSection": "abstract" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1357, "text": "CONCLUSIONS: Our results support the hypothesis of an association between infection with CagA-positive H. pylori strains and acute cerebral ischemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15166387", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1315, "text": " Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500942", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1395, "text": "CONCLUSIONS: Infection with Helicobacter pylori is associated with an increased risk of stroke and increased fibrinogen levels but these findings can be attributed to a confounding effect of socio-economic status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12725602", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1698, "text": " CONCLUSIONS: Hp infection represents risk factor of ischemic stoke via an interaction of Hp cytotoxins or cytokines with atherosclerotic plaques in carotic arteries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12388919", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1608, "text": "CONCLUSIONS: The association between H pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H pylori strains in patients with atherosclerotic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12147540", "endSection": "abstract" }, { "offsetInBeginSection": 1748, "offsetInEndSection": 1891, "text": "CONCLUSIONS: H. pylori infection appears to be significantly more frequent in middle-aged patients with acute ischemic stroke than in controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12063957", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1353, "text": "Chronic H pylori infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not associated with ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11588309", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 188, "text": "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11412864", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1101, "text": " H. pylori seropositivity may be an independent risk factor for stroke of atherothrombotic origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11412864", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1452, "text": "Appropriately randomized studies employing an antibiotic treatment for patients affected by ischemic vascular disease will answer the question of whether H. pylori has a causal role in the pathogenesis of acute myocardial infarction and ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11253332", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 579, "text": "Results on the association between this bacterium and acute myocardial infarction or stroke are controversial, due to the degree of studies heterogeneity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11155465", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 1010, "text": "Interventional randomized studies employing an antibiotic treatment for patients affected by ischemic vascular diseases will rapidly answer the question of wheather Helicobacter pylori has a causal role in the pathogenesis of acute myocardial infarction and ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11155465", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1584, "text": " CONCLUSION: Chronic H pylori infection is an independent risk factor for ischaemic cerebrovascular disease and may act, at least in part, by increasing atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9436737", "endSection": "abstract" }, { "offsetInBeginSection": 59, "offsetInEndSection": 187, "text": "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11412864", "endSection": "abstract" }, { "offsetInBeginSection": 2048, "offsetInEndSection": 2177, "text": "This case-control study does not reveal any strong association between chronic Helicobacter pylori infection and ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 237, "text": "However, there are conflicting results on the relevance of chronic infection by Helicobacter pylori as a risk factor for ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1314, "text": "Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15166387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "This case-control study does not reveal any strong association between chronic Helicobacter pylori infection and ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 186, "text": "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11412864", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 487, "text": "Chronic infectious diseases that may increase the risk of stroke include periodontitis, chronic bronchitis and infections with microbial antigens, such as Helicobacter pylori and Chlamydia pneumoniae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16466297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15166387", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 187, "text": "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11412864", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 237, "text": "However, there are conflicting results on the relevance of chronic infection by Helicobacter pylori as a risk factor for ischemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "endSection": "abstract" } ] }, { "body": "Which are the major types of the motor speech disorder dysarthria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1809779", "http://www.ncbi.nlm.nih.gov/pubmed/24222784", "http://www.ncbi.nlm.nih.gov/pubmed/9197089", "http://www.ncbi.nlm.nih.gov/pubmed/22268902", "http://www.ncbi.nlm.nih.gov/pubmed/23422471", "http://www.ncbi.nlm.nih.gov/pubmed/10693258", "http://www.ncbi.nlm.nih.gov/pubmed/22774423", "http://www.ncbi.nlm.nih.gov/pubmed/21088427", "http://www.ncbi.nlm.nih.gov/pubmed/19995207", "http://www.ncbi.nlm.nih.gov/pubmed/19295217", "http://www.ncbi.nlm.nih.gov/pubmed/18953144", "http://www.ncbi.nlm.nih.gov/pubmed/20184513", "http://www.ncbi.nlm.nih.gov/pubmed/23312647", "http://www.ncbi.nlm.nih.gov/pubmed/23033442", "http://www.ncbi.nlm.nih.gov/pubmed/20882349" ], "ideal_answer": [ "Dysarthria is a motor speech disorder which can be classified according to the underlying neuropathology and is associated with disturbances of respiration, laryngeal function, airflow direction, and articulation resulting in difficulties of speech quality and intelligibility. There are six major types of dysarthria: \"flaccid dysarthria\" associated with lower motor neuron impairment, \"spastic dysarthria\" associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, \"ataxic dysarthria\" primarily caused by cerebellar dysfunction, and \"hyperkinetic dysarthria\" and \"hypokinetic dysarthria\", which are related to a disorder of the extrapyramidal system. The sixth is generally termed a \"mixed dysarthria\" and is associated with damage in more than one area, resulting in speech characteristics of at least two groups." ], "exact_answer": [ [ "flaccid dysarthria" ], [ "spastic dysarthria" ], [ "ataxic dysarthria" ], [ "hyperkinetic dysarthria" ], [ "hypokinetic dysarthria" ], [ "mixed dysarthria" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:92", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004401", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013064" ], "type": "list", "id": "5547d700f35db75526000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 839, "text": "Dysarthria is a motor speech disorder which can be classified according to the underlying neuropathology and is associated with disturbances of respiration, laryngeal function, airflow direction, and articulation resulting in difficulties of speech quality and intelligibility. There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system. The sixth is generally termed a mixed dysarthria and is associated with damage in more than one area, resulting in speech characteristics of at least two groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312647", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 315, "text": "address voice problems of stroke patients with mixed dysarthria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Characterizing intonation deficit in motor speech disorders: an autosegmental-metrical analysis of spontaneous speech in hypokinetic dysarthria, ataxic dysarthria", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23033442", "endSection": "title" }, { "offsetInBeginSection": 359, "offsetInEndSection": 381, "text": "ataxic dysarthria (AT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23033442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Acoustic analysis provides objective quantitative measures of speech that enable a comprehensive and accurate understanding of motor disorders and complement the traditional measures. This paper aims to distinguish between normal and pathological speech, more specifically between apraxia of speech and spastic dysarthria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22774423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Long-term phonatory instability in ataxic dysarthria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21088427", "endSection": "title" }, { "offsetInBeginSection": 97, "offsetInEndSection": 209, "text": "The objective of this study is to evaluate phonation in ataxic dysarthria and a control group of normal speakers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21088427", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 83, "text": "Dysprosody is a common feature in speakers with hypokinetic dysarthria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19995207", "endSection": "abstract" }, { "offsetInBeginSection": 1354, "offsetInEndSection": 1487, "text": "The prosodic profile of Cantonese speakers with hypokinetic dysarthria is similar to those of other languages (for example, English).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19995207", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 127, "text": "Classification of dysarthria types comprises flaccid, spastic, ataxic, hypo- and hyperkinetic and mixed dysarthria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19295217", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 217, "text": "Dysarthria affects linguistic domains such as respiration, phonation, articulation, resonance and prosody due to upper motor neuron, lower motor neuron, cerebellar or extrapyramidal tract lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953144", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1305, "text": "The dysarthria types were spastic (15 subjects), flaccid (10), mixed (12), hypokinetic (12), hyperkinetic (9) and ataxic (8).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Dysarthria is a motor speech disorder which can be classified according to the underlying neuropathology and is associated with disturbances of respiration, laryngeal function, airflow direction, and articulation resulting in difficulties of speech quality and intelligibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312647", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 676, "text": "There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312647", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 677, "text": "There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Motor neuron disease encompasses a group of terminal, demyelinating diseases affecting upper- and lower-motor neurons and producing muscular weakness resulting in a flaccid, spastic, or spastic-flaccid dysarthria of speech.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1809779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Dysarthria is a frequently occurring motor speech disorder which can be caused by neurological trauma, cerebral palsy, or degenerative neurological diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24222784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Dysarthria is a motor disorder of speech characterized by abnormalities of the articulation and intelligibility of speech.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20184513", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 676, "text": "There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312647", "endSection": "abstract" } ] }, { "body": "Is oxidative stress affected by FOXO expression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16709600", "http://www.ncbi.nlm.nih.gov/pubmed/19842039", "http://www.ncbi.nlm.nih.gov/pubmed/24269635", "http://www.ncbi.nlm.nih.gov/pubmed/22986347" ], "ideal_answer": [ "Yes. In different cell types, induction of forkhead transcription factor FOXO1 was found to increase expression of the mitochondrial antioxidant manganese superoxide dismutase, and lead to suppression of oxidative stress." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/FOXO_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006979", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034599", "http://www.uniprot.org/uniprot/FOXO_CAEEL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900407", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018384" ], "type": "yesno", "id": "5316111fb166e2b806000001", "snippets": [ { "offsetInBeginSection": 65, "offsetInEndSection": 237, "text": "Forkhead-box class O (FoxO) transcription factors regulate mechanisms of cellular aging, including protein quality control, autophagy and defenses against oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24269635", "endSection": "abstract" }, { "offsetInBeginSection": 1306, "offsetInEndSection": 1454, "text": "Statin-mediated upregulation of klotho expression and differential regulation of FoxO expression promote resistance to CsA-induced oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22986347", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1612, "text": "FoxO expression suppressed the ROS-induced apoptosis in differentiated 3T3-L1 cells via the expression of ROS-scavenging enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16709600", "endSection": "title" }, { "offsetInBeginSection": 246, "offsetInEndSection": 647, "text": "We demonstrate that human endometrial stromal cells become extraordinarily resistant to oxidative stress-induced apoptosis upon decidualization in response to cAMP and progesterone signaling. This differentiation process is associated with the induction of the forkhead transcription factor FOXO1, which in turn increases the expression of the mitochondrial antioxidant manganese superoxide dismutase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16709600", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 978, "text": "Comparative analysis demonstrated that hydrogen peroxide, a source of free radicals, strongly induces FOXO3a mRNA and protein expression in undifferentiated human endometrial stromal cells but not in decidualized cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16709600", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1609, "text": "These results suggest that the induction of FOXO1 may enhance the ability of decidualized cells to prevent oxidative damage while the simultaneous repression of FOXO3a expression disables the signaling pathway responsible for oxidative cell death. The differential regulation of FOXO expression provides the decidua with a robust system capable of coping with prolonged episodes of oxidative stress during pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16709600", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of the LINX system for treatment of gastroesophageal reflux disease.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23155537", "http://www.ncbi.nlm.nih.gov/pubmed/22538694", "http://www.ncbi.nlm.nih.gov/pubmed/24117632", "http://www.ncbi.nlm.nih.gov/pubmed/21037442", "http://www.ncbi.nlm.nih.gov/pubmed/25062898", "http://www.ncbi.nlm.nih.gov/pubmed/24778041", "http://www.ncbi.nlm.nih.gov/pubmed/19951799", "http://www.ncbi.nlm.nih.gov/pubmed/25000345", "http://www.ncbi.nlm.nih.gov/pubmed/25012804", "http://www.ncbi.nlm.nih.gov/pubmed/23814607", "http://www.ncbi.nlm.nih.gov/pubmed/23237251", "http://www.ncbi.nlm.nih.gov/pubmed/25264655" ], "ideal_answer": [ "LINX Reflux Management System is a sphincter augmentation device designed to prevent gastroesophageal reflux due to abnormal opening of the lower esophageal sphincter (LES) by augmenting the sphincter barrier. It is implanted via laparoscopic procedure that does not alter gastric anatomy and is easily reversible." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8534" ], "type": "summary", "id": "54e22ee4ae9738404b000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Magnetic sphincter augmentation with the LINX device for gastroesophageal reflux disease after U.S. Food and Drug Administration approval.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25264655", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Magnetic sphincter augmentation (MSA) of the gastroesophageal junction with the LINX Reflux Management System is an alternative to fundoplication for gastroesophageal reflux disease (GERD) that was approved by the U.S. Food and Drug Administration (FDA) in March 2012. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25264655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Is the LINX reflux management system an effective treatment for gastro-oesophageal reflux disease?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25062898", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Laparoscopic magnetic sphincter augmentation (MSA) with the LINX device is a promising new therapy for the treatment of gastroesophageal reflux disease (GERD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012804", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 664, "text": "Other nonmedical therapies include, the Stretta procedure, transoral incisionless fundoplication, and the magnetic sphincter augmentation device (LINX). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25000345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "LINX(\u00ae) Reflux Management System in chronic gastroesophageal reflux: a novel effective technology for restoring the natural barrier to reflux.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23814607", "endSection": "title" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1206, "text": " The LINX(\u00ae) Reflux Management System (Torax Medical, St. Paul, MN, USA) is designed to provide a permanent solution to GERD by augmenting the sphincter barrier with a standardized, reproducible laparoscopic procedure that does not alter gastric anatomy and is easily reversible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23814607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "LINX(\u2122) Reflux Management System: magnetic sphincter augmentation in the treatment of gastroesophageal reflux disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23237251", "endSection": "title" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1267, "text": "The LINX(\u2122) Reflux Management System (Torax Medical) is designed to provide a permanent solution to GERD by augmenting the physiologic function of the sphincter barrier with a simple and reproducible laparoscopic procedure that does not alter gastric anatomy and can be easily reversed if necessary.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23237251", "endSection": "abstract" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1436, "text": "The Linx sphincter augmentation device has been developed to address this gap with improvement of the barrier function of LES and reversible design if necessary.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23155537", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 575, "text": " METHODS: A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21037442", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 357, "text": "Specific topics include reviews of long-term outcomes after laparoscopic antireflux surgery, the use of surgically placed implantable device for LES augmentation (Linx), the use of mesh for hiatal hernioplasty, and prone and nonthoracic approaches to minimally invasive esophagectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19951799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "LINX( ) Reflux Management System: magnetic sphincter augmentation in the treatment of gastroesophageal reflux disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23237251", "endSection": "title" }, { "offsetInBeginSection": 300, "offsetInEndSection": 575, "text": "METHODS: A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21037442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "BACKGROUND: Sphincter augmentation with the LINX\ufffd Reflux Management System is a surgical option for patients with chronic gastroesophageal disease (GERD) and an inadequate response to proton pump inhibitors (PPIs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22538694", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 554, "text": "A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21037442", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1488, "text": "Sphincter augmentation with the LINX Reflux Management System provided long-term clinical benefits with no safety issues, as demonstrated by reduced esophageal acid exposure, improved GERD-related quality of life, and cessation of dependence on PPIs, with minimal side effects and no safety issues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22538694", "endSection": "abstract" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1436, "text": "The limitations of current therapy for GERD have encouraged a search for more effective treatment.The Linx sphincter augmentation device has been developed to address this gap with improvement of the barrier function of LES and reversible design if necessary.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23155537", "endSection": "abstract" } ] }, { "body": "Which enzyme deficiency can cause GM1 gangliosidoses?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10571006", "http://www.ncbi.nlm.nih.gov/pubmed/2837434", "http://www.ncbi.nlm.nih.gov/pubmed/8112731", "http://www.ncbi.nlm.nih.gov/pubmed/1909089", "http://www.ncbi.nlm.nih.gov/pubmed/10757351", "http://www.ncbi.nlm.nih.gov/pubmed/17442056", "http://www.ncbi.nlm.nih.gov/pubmed/8068159", "http://www.ncbi.nlm.nih.gov/pubmed/2117086", "http://www.ncbi.nlm.nih.gov/pubmed/117628", "http://www.ncbi.nlm.nih.gov/pubmed/2123760", "http://www.ncbi.nlm.nih.gov/pubmed/1588015", "http://www.ncbi.nlm.nih.gov/pubmed/3088302", "http://www.ncbi.nlm.nih.gov/pubmed/25936995", "http://www.ncbi.nlm.nih.gov/pubmed/23622392", "http://www.ncbi.nlm.nih.gov/pubmed/3084261", "http://www.ncbi.nlm.nih.gov/pubmed/15086521" ], "ideal_answer": [ "GM1 gangliosidoses are associated with deficiency of \u03b2-galactosidase." ], "exact_answer": [ "\u03b2-galactosidase" ], "type": "factoid", "id": "571f609c0fd6f91b6800000c", "snippets": [ { "offsetInBeginSection": 272, "offsetInEndSection": 382, "text": "GM1 and GM2 gangliosidosis are associated with deficiency of \u03b2-galactosidase and \u03b2-hexosaminidase respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23622392", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 257, "text": "The total content and distribution of retinal glycosphingolipids was studied for the first time in control mice and in Sandhoff disease (SD) and GM1 gangliosidosis mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17442056", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1056, "text": "The GSL abnormalities in the SD and the GM1 retinas reflect significant reductions in beta-hexosaminidase and beta-galactosidase enzyme activities, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17442056", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 911, "text": "In the absence of macular or retinal degeneration, organomegaly, and somatic-facial features suggesting mucopolysaccharidosis, the presence of hyperacusis together with sea-blue histiocytes in bone marrow biopsies and deficient beta-galactosidase activity but normal glucosidase, hexosaminidase, and neuraminidase activity on lysosomal enzyme assays constitutes the clinical-pathologic-biochemical profile of GM1 gangliosidosis type 2. This is a rare, late infantile onset, progressive gray-matter disease in which beta-galactosidase deficiency is largely localized to the brain, though it can be demonstrated in leukocytes and cultured skin fibroblasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1588015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "GM1-gangliosidosis (genetic beta-galactosidase deficiency)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1909089", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "GM1-gangliosidosis is a genetic neurological disorder caused by mutations in the lysosomal acid beta-galactosidase gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1909089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "GM1-gangliosidosis is a rare neurovisceral storage disease caused by an inherited deficiency of acid beta-galactosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2123760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "A female infant with early-onset GM1-gangliosidosis type I was investigated. The lymphocytes, transformed lymphocytes and cultured skin fibroblasts of the patient were demonstrated to have severe beta-D-galactosidase deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2117086", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 801, "text": "Only 1 individual was found to have about 50% of normal beta-galactosidase activity; presumably he is a carrier for beta-galactosidase deficiency (GM1 gangliosidosis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2837434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme \u03b2-d-galactosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25936995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "GM1 gangliosidosis is a genetic disease with lysosomal beta-galactosidase deficiency caused by mutations of the gene coding for this enzyme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8068159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid beta-galactosidase (beta-gal), the enzyme that catabolyzes GM1 within lysosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15086521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Correction of acid beta-galactosidase deficiency in GM1 gangliosidosis human fibroblasts by retrovirus vector-mediated gene transfer: higher efficiency of release and cross-correction by the murine enzyme", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10757351", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Review of the data is presented on the hereditary disease gangliosidosis GM1 and on the enzyme beta-galactosidose, deficiency of which is responsible for this disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/117628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "GM1 gangliosidosis and Morquio B disease are distinct disorders both clinically and biochemically yet they arise from the same beta-galactosidase enzyme deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10571006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Heterogeneous patterns of biosynthesis, posttranslational processing, and degradation were demonstrated for mutant enzymes in three clinical forms of beta-galactosidase deficiency (beta-galactosidosis): juvenile GM1-gangliosidosis, adult GM1-gangliosidosis, and Morquio B disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8112731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "GM1 gangliosidosis and Morquio B disease are distinct disorders both clinically and biochemically yet they arise from the same beta-galactosidase enzyme deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10571006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Cerebral lipids of patients with GM1-gangliosidoses, infantile, juvenile, and chronic type which are caused by deficiency of beta-galactosidase, were examined and compared to each other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3088302", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 848, "text": "In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface. The lysosomes remain unlabeled, indicative for the absence of enzyme molecules in this organelle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3084261", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 750, "text": "In the lysosomes virtually all beta-gal exists as a high molecular weight multimer of mature enzyme. In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3084261", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 750, "text": "In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3084261", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 384, "text": "GM1 and GM2 gangliosidosis are associated with deficiency of \u03b2-galactosidase and \u03b2-hexosaminidase respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23622392", "endSection": "abstract" } ] }, { "body": "What is the characteristic feature of the Dyke-Davidoff-Masson syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25207154", "http://www.ncbi.nlm.nih.gov/pubmed/23672850", "http://www.ncbi.nlm.nih.gov/pubmed/20691943", "http://www.ncbi.nlm.nih.gov/pubmed/21764333", "http://www.ncbi.nlm.nih.gov/pubmed/15869006", "http://www.ncbi.nlm.nih.gov/pubmed/7761171", "http://www.ncbi.nlm.nih.gov/pubmed/7214933", "http://www.ncbi.nlm.nih.gov/pubmed/15158218", "http://www.ncbi.nlm.nih.gov/pubmed/19204321", "http://www.ncbi.nlm.nih.gov/pubmed/23591309", "http://www.ncbi.nlm.nih.gov/pubmed/10029885", "http://www.ncbi.nlm.nih.gov/pubmed/22967682", "http://www.ncbi.nlm.nih.gov/pubmed/20236868", "http://www.ncbi.nlm.nih.gov/pubmed/23189018", "http://www.ncbi.nlm.nih.gov/pubmed/17250509", "http://www.ncbi.nlm.nih.gov/pubmed/24419451", "http://www.ncbi.nlm.nih.gov/pubmed/12763349", "http://www.ncbi.nlm.nih.gov/pubmed/15798614", "http://www.ncbi.nlm.nih.gov/pubmed/11814746", "http://www.ncbi.nlm.nih.gov/pubmed/21559157", "http://www.ncbi.nlm.nih.gov/pubmed/24891488", "http://www.ncbi.nlm.nih.gov/pubmed/1547482", "http://www.ncbi.nlm.nih.gov/pubmed/16100487", "http://www.ncbi.nlm.nih.gov/pubmed/19744394", "http://www.ncbi.nlm.nih.gov/pubmed/8997138", "http://www.ncbi.nlm.nih.gov/pubmed/23344879", "http://www.ncbi.nlm.nih.gov/pubmed/19029569", "http://www.ncbi.nlm.nih.gov/pubmed/19169186", "http://www.ncbi.nlm.nih.gov/pubmed/24257011", "http://www.ncbi.nlm.nih.gov/pubmed/22681314", "http://www.ncbi.nlm.nih.gov/pubmed/19097769", "http://www.ncbi.nlm.nih.gov/pubmed/24977128" ], "ideal_answer": [ "Cerebral hemiatrophy (atrophy of one cerebral hemisphere) is the characteristic feature of the Dyke-Davidoff-Masson syndrome. It develops due to an insult to the brain in fetal or early childhood period. Calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures are also characteristic to the Dyke-Davidoff-Masson syndrome.\n." ], "exact_answer": [ "cerebral hemiatrophy" ], "type": "factoid", "id": "55032e65e9bde69634000034", "snippets": [ { "offsetInBeginSection": 202, "offsetInEndSection": 402, "text": "Dyke-Davidoff-Masson syndrome is a rare condition characterized by cerebral hemiatrophy, calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23672850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Dyke-Davidoff-Masson syndrome refers to atrophy of one cerebral hemisphere (hemiatrophy) due to an insult to the brain in fetal or early childhood period. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Acquired cerebral hemiatrophy: Dyke-Davidoff-Masson Syndrome - a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23344879", "endSection": "title" }, { "offsetInBeginSection": 620, "offsetInEndSection": 730, "text": "CT and MRI scan of the head showed hemiatrophic cerebral parenchyma with prominent sulci and encephalomalacia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23344879", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 298, "text": "CT of the brain revealed characteristic features diagnostic of infantile type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23189018", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 728, "text": "Magnetic resonance imaging (MRI) of brain revealed atrophic of left cerebral hemisphere with mildly ventricular dilatation, prominent paranasal and mastoid air cells, suggestive of Dyke-Davidoff-Masson syndrome (DDMS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22967682", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1271, "text": "Imaging showed resolution of the infection and features of Dyke-Davidoff-Masson syndrome (cerebral hemiatrophy). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22681314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Dyke-Davidoff-Masson syndrome (DDMS) is a rare epilepsy syndrome that is characterized by cerebral hemiatrophy, homolateral skull hyperplasia, hyperpneumatization of the paranasal sinuses, seizures with or without mental retardation, and contralateral hemiparesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764333", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 857, "text": "Brain MRI showed prominent atrophy in the left frontal dorsal and lateral regions and mild atrophy of the left superior temporal gyrus and left parietal gyri.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "A 15-year-old female presented with seizures, right-sided hemiparesis, hemiatrophy of the right side of the body and mental retardation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21559157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Described here is the case of a girl with a reticulated capillary malformation on the right side of her face, along with Dyke-Davidoff-Masson syndrome, as evidenced by microphthalmia and severe associated anomalies in the right eye, and right cerebral hemispheric atrophy and cerebral arteries malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The purpose of this study was to retrospectively evaluate the cognitive and electroclinical characteristics of right cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome [DDMS]). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20236868", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 810, "text": "The CHA of childhood or Dyke-Davidoff-Masson syndrome, is originated by intrauterine or perinatal insults that affect the perfusion of a single cerebral hemisphere, manifesting clinically by variable mental retardation, refractory epilepsy, facial asymmetry, hemiplegia/hemiparesis or abnormal movements of the contralateral extremities and by imaging studies, loss of volume in one cerebral hemisphere and ipsilateral compensatory cranial changes such as skull vault thickening, elevation of the orbital roof and petreous ridge, also hyperpneumatization of the frontal sinus and mastoid cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19744394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "Dyke-Davidoff-Masson syndrome is a disorder involving hemiatrophy or hypoplasia of 1 cerebral hemisphere secondary to an insult in the developing brain. Often this will manifest with seizures, hemiparesis, mental retardation, and facial changes. Associated with this pathology are the radiologically evident changes, such as thickening of the calvarium, hyperpneumatization of the sinuses, and dilation of the ipsilateral lateral ventricle among others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19204321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Dyke-Davidoff-Masson syndrome, or cerebral hemiatrophy, is a pre- or perinatally acquired entity characterized by predominantly neurologic symptoms, such as seizures, facial asymmetry, contralateral hemiplegia, and mental retardation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "The Dyke-Davidoff-Masson syndrome is characterized by various symptoms related to hemiatrophy of the cerebrum and hypertrophy of the ipsilateral calvarium and paranasal sinuses. Clinical findings include hemiparesis or hemiplegia, seizures and/or mental retardation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19097769", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 572, "text": "Asymmetry of cerebral hemispheric growth with atrophy on one side, ipsilateral osseous hypertrophy and hyper-pneumatization of sinuses with contralateral paresis are features of Dyke Davidoff Masson Syndrome (DDMS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 402, "text": "Dyke Davidoff Masson syndrome (DDMS) is characterized by seizures, facial asymmetry, contralateral hemiplegia and mental retardation. The characteristic radiologic features are cerebral hemiatrophy with homolateral hypertrophy of the skull and sinuses. We report a case of DDMS in an 18-month-old girl who presented with right sided focal seizures, hemiparesis of the same side, and delayed milestones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19029569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome) in childhood: clinicoradiological analysis of 19 cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17250509", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "The so-called Dyke-Davidoff-Masson syndrome (DDMS) is a rare disorder of cerebral hemiatrophy. The clinical presentation may consist of facial asymmetry, contralateral atrophy (including the trunk, and the extremities) and hemiparesis, speech difficulties, mental retardation, and epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15869006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Dyke-Davidoff-Masson syndrome is clinically characterized by hemiparesis, hemiplegia, seizures, mental retardation, and facial asymmetry secondary to congenital or early childhood vascular insult. A 21-year-old man with Dyke-Davidoff-Masson syndrome presented with uncontrolled seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16100487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis and mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15798614", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 408, "text": "Brain MRI showed unilateral loss of cerebral volume with hypertrophy and hyperpneumatization of the paranasal sinuses and mastoid cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15798614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Although radiological findings of cerebral hemiatrophy (Dyke-Davidoff-Masson Syndrome) are well known, there is no systematic study about the gender and the affected side in this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15158218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 635, "text": "The patient was a 19-year-old woman who presented with hemiatrophy and diminished superficial sensation on the left side of her body including her face. She had a past history of tonic-clonic seizures accompanied by left hemiparesis in late childhood. Brain CT demonstrated dilatation of the frontal sinus, calvarial thickening, cerebral hemiatrophy and dilatation of the lateral ventricle on the right side. Brain MRI showed atrophy of the right cerebrum and midbrain and dilatation of the lateral ventricle on T1-weighted images, as well as a high signal intensity area from the parietal to the occipital lobe on T2-weighted images. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12763349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis, and mental retardation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10029885", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 507, "text": "The radiological features are unilateral loss of cerebral volume and associated compensatory bone alterations in the calvarium, like thickening, hyperpneumatization of the paranasal sinuses and mastoid cells and elevation of the petrous ridge. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10029885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "We reported a 39-year-old man with Dyke-Davidoff-Masson syndrome presenting with total hemiatrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8997138", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 623, "text": "This paper presents an 18-year-old mentally retarded patient with cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome) associated with a growing skull fracture in the ipsilateral hemicranium, in whom not only a dural tear but also the ipsilaterally displaced and dilated lateral ventricle due to the original disease apparently contributed to the development of growing skull fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7761171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The magnetic resonance (MR) findings of three patients with cerebral hemiatrophy, the so-called Dyke-Davidoff-Masson syndrome, which is characterized by variable degrees of unilateral loss of cerebral volume and compensatory changes of the calvarium are presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1547482", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 267, "text": "MRI brain revealed characteristic features diagnostic of congenital type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21559157", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1270, "text": "Imaging showed resolution of the infection and features of Dyke-Davidoff-Masson syndrome (cerebral hemiatrophy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22681314", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 571, "text": "Asymmetry of cerebral hemispheric growth with atrophy on one side, ipsilateral osseous hypertrophy and hyper-pneumatization of sinuses with contralateral paresis are features of Dyke Davidoff Masson Syndrome (DDMS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257011", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 296, "text": "CT of the brain revealed characteristic features diagnostic of infantile type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23189018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Dyke-Davidoff-Masson syndrome refers to atrophy of one cerebral hemisphere (hemiatrophy) due to an insult to the brain in fetal or early childhood period", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591309", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 726, "text": "Magnetic resonance imaging (MRI) of brain revealed atrophic of left cerebral hemisphere with mildly ventricular dilatation, prominent paranasal and mastoid air cells, suggestive of Dyke-Davidoff-Masson syndrome (DDMS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22967682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Dyke-Davidoff-Masson syndrome is a relatively rare syndrome with its typical clinical and radiological features including facial asymmetry, hemiplegia, cerebral hemiatrophy, mental retardation with calvarial thickening, hypertrophy of sinuses and elevated petrous ridge on imaging", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24419451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The purpose of this study was to retrospectively evaluate the cognitive and electroclinical characteristics of right cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome [DDMS])", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20236868", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 853, "text": "We describe a female infant with prenatal diagnosis of unilateral left ventriculomegaly in which early brain MRI and contrast enhanced-MRI angiography, showed cerebral left hemiatrophy associated with reduced caliber of the left middle cerebral artery revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23672850", "endSection": "abstract" } ] }, { "body": "Which gene is involved in the development of Barth syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20981509", "http://www.ncbi.nlm.nih.gov/pubmed/24342716", "http://www.ncbi.nlm.nih.gov/pubmed/23523468", "http://www.ncbi.nlm.nih.gov/pubmed/24813252", "http://www.ncbi.nlm.nih.gov/pubmed/24093814", "http://www.ncbi.nlm.nih.gov/pubmed/24801725", "http://www.ncbi.nlm.nih.gov/pubmed/25941633", "http://www.ncbi.nlm.nih.gov/pubmed/16857210", "http://www.ncbi.nlm.nih.gov/pubmed/22023389", "http://www.ncbi.nlm.nih.gov/pubmed/16442164", "http://www.ncbi.nlm.nih.gov/pubmed/16794186", "http://www.ncbi.nlm.nih.gov/pubmed/25247053", "http://www.ncbi.nlm.nih.gov/pubmed/25776009" ], "ideal_answer": [ "Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause Barth syndrome (BTHS)", "Tafazzin, a mitochondrial acyltransferase encoded by a gene of the same name, plays an important role in cardiolipin side chain remodeling. Studies have shown that mutation-induced dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome (BTHS)." ], "exact_answer": [ "Tafazzin (TAZ) gene" ], "type": "factoid", "id": "5717d86029809bbe7a000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause Barth syndrome (BTHS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25941633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25247053", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 422, "text": "we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24813252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16794186", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523468", "endSection": "title" }, { "offsetInBeginSection": 758, "offsetInEndSection": 1006, "text": "This resynthesis of deacylated cardiolipin from monolysocardiolipin occurs via the Barth Syndrome gene product tafazzin and acyllysocardiolipin acyltransferase-1, monolysocardiolipin acyltransferase-1 and the alpha subunit of trifunctional protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24801725", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1719, "text": "We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25247053", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 715, "text": "Here, we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24813252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Mutations in the human TAZ gene are associated with Barth Syndrome, an often fatal X-linked disorder that presents with cardiomyopathy and neutropenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16857210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "A Novel TAZ Gene Mutation and Mosaicism in a Polish Family with Barth Syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25776009", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523468", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Barth syndrome is caused by mutations in the TAZ (tafazzin) gene on human chromosome Xq28", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24342716", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 185, "text": "BTHS is caused by loss-of-function mutations of the tafazzin (TAZ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023389", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 562, "text": "This abnormality involves the deletion of the bases TGA starting at cDNA nucleotide 891 (c891_893delTGA), resulting in the absence of glutamic acid at codon 202 from a highly conserved area of the tafazzin protein, consistent with the diagnosis of Barth syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Novel mutations in the TAZ gene in patients with Barth syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24093814", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16794186", "endSection": "title" }, { "offsetInBeginSection": 673, "offsetInEndSection": 783, "text": "The Barth Syndrome gene TAZ has been identified and expression of the gene yields proteins known as tafazzins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16442164", "endSection": "abstract" } ] }, { "body": "What is the treatment of subacute thyroiditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17923793", "http://www.ncbi.nlm.nih.gov/pubmed/22138076", "http://www.ncbi.nlm.nih.gov/pubmed/22313427", "http://www.ncbi.nlm.nih.gov/pubmed/23227861" ], "ideal_answer": [ "Common treatment of subacute thyroiditis is with anti-inflammatory drug agents, namely corticosteroids" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:7187", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364", "http://www.disease-ontology.org/api/metadata/DOID:7166", "http://www.disease-ontology.org/api/metadata/DOID:7165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013959", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042493", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013968", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013956" ], "type": "summary", "id": "51406dd123fec90375000008", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 108, "text": "Oral glucocorticoids are administered in moderate and severe cases of subacute thyroiditis (SAT)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227861", "endSection": "sections.0" }, { "offsetInBeginSection": 1841, "offsetInEndSection": 1984, "text": "he treatment protocol that we employed had 15 mg/day of PSL as the initial dosage for the treatment of SAT, with tapering by 5 mg every 2 weeks", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227861", "endSection": "sections.0" } ] }, { "body": "What are the effects of BMAL1 deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22611086", "http://www.ncbi.nlm.nih.gov/pubmed/24481314", "http://www.ncbi.nlm.nih.gov/pubmed/20576619", "http://www.ncbi.nlm.nih.gov/pubmed/21149897", "http://www.ncbi.nlm.nih.gov/pubmed/22101268", "http://www.ncbi.nlm.nih.gov/pubmed/20519775" ], "ideal_answer": [ "BMAL1 deficiency is associated with premature aging and reduced lifespan and BMAL1 deficiency leads to development of stress induced senescence in vivo. Down-regulation of Bmal1 also accelerates the development of tumours, adipogenesis." ], "type": "summary", "id": "56e45bc651531f7e33000018", "snippets": [ { "offsetInBeginSection": 224, "offsetInEndSection": 296, "text": "BMAL1 deficiency is associated with premature aging and reduced lifespan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24481314", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1314, "text": "BMAL1 deficiency leads to development of stress induced senescence in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22101268", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1143, "text": " Down-regulation of Bmal1 accelerates the development of tumours ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20576619", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 281, "text": "BMAL1 deficiency results in premature aging in mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149897", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1437, "text": "BMAL1 deficiency disrupts circadian oscillation in gene expression and reactive oxygen species homeostasis in the brain,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20519775", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 774, "text": "We demonstrate that attenuation of Bmal1 function resulted in down-regulation of genes in the canonical Wnt pathway, known to suppress adipogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22611086", "endSection": "abstract" } ] }, { "body": "Which histone modifications are associated with Polycomb group (PcG) proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23104054", "http://www.ncbi.nlm.nih.gov/pubmed/19723660", "http://www.ncbi.nlm.nih.gov/pubmed/17525233", "http://www.ncbi.nlm.nih.gov/pubmed/20385584", "http://www.ncbi.nlm.nih.gov/pubmed/16537902", "http://www.ncbi.nlm.nih.gov/pubmed/23322639", "http://www.ncbi.nlm.nih.gov/pubmed/23694722" ], "ideal_answer": [ "A member of the polycomb repressive complex 2 (PRC2) directly mediates the addition of K27me3 to histone H3, a modification associated with heterochromatin, and it is believed that this activity mediates transcriptional repression. At the same time PRC2 activity results in a global increase in H3K27 acetylation. Some members of the PcG display affinity towards both histone H3 trimethylated at K9 and H3K27me3, and one CD prefers K9me3." ], "exact_answer": [ [ "H3K27me3" ], [ "H3K27Ac" ], [ "H3K9me3" ], [ "H3K36me" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031519", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063146", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016573", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016570", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016571", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035102" ], "type": "list", "id": "531b1e3cb166e2b80600003b", "snippets": [ { "offsetInBeginSection": 267, "offsetInEndSection": 521, "text": "The PcG proteins are well-conserved chromatin factors that repress transcription of numerous target genes. They bind the genome at specific sites, forming chromatin domains of associated histone modifications as well as higher-order chromatin structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23694722", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 994, "text": "A component of Polycomb repressive complex 2 (PRC2), which mediates the addition of K27me3 to histone H3 (Suz12), was also recruited by 14 dpi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322639", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1381, "text": "We found that a component of the PRC1 complex (Bmi1), which binds to H3K27me3, was not enriched at promoters found previously to be enriched for H3K27me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322639", "endSection": "abstract" }, { "offsetInBeginSection": 1837, "offsetInEndSection": 2080, "text": " Here we show that the HSV DNA first associates with histone H3, with later recruitment of Polycomb repressor complex 2 (PRC2) and trimethylation of the lysine 27 residue of histone H3 (H3K27me3), a modification associated with heterochromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322639", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 506, "text": "Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104054", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 755, "text": "Furthermore, we show that Phf19 binds to a subset of PRC2 targets in mouse embryonic stem cells and that this is required for their repression and for H3K27me3 deposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104054", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 382, "text": "The Polycomb repressive complex 2 (PRC2) catalyzes trimethylation (me3) of histone H3 lysine 27 (K27), and it is believed that this activity mediates transcriptional repression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385584", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 896, "text": "We show that loss of PRC2 activity results in a global increase in H3K27 acetylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385584", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1204, "text": "Moreover, we provide evidence that the acetylation of H3K27 is catalyzed by the acetyltransferases p300 and CBP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385584", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1490, "text": "Taken together, these studies suggest that patterns of epigenetic modifiers and the histone code influence the propensity of a gene to become hypermethylated in cancer and that DNMT3B plays an important role in regulating PRC1 function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19723660", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 296, "text": "During differentiation, binding of polycomb repressive complex 2 (PRC2), which mediates trimethylation of lysine 27 on histone H3 (K27me3), is lost on developmental genes that are transcriptionally induced", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525233", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 142, "text": "chromodomain (CD) of the Drosophila Polycomb protein exhibits preferential binding affinity for histone H3 when trimethylated at lysine 27", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16537902", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 518, "text": "Not all CDs bind preferentially to K27me3; rather, some display affinity towards both histone H3 trimethylated at K9 and H3K27me3, and one CD prefers K9me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16537902", "endSection": "abstract" } ] }, { "body": "Where is the protein CLIC1 localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21055175", "http://www.ncbi.nlm.nih.gov/pubmed/15827065", "http://www.ncbi.nlm.nih.gov/pubmed/9880541" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q5E9B7", "o": "http://linkedlifedata.com/resource/#_51354539423700E" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51354539423700E", "o": "CLIC1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51354539423700C", "o": "Chloride intracellular channel protein 1" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q95MF9", "o": "http://linkedlifedata.com/resource/#_5139354D463900A" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5139354D463900A", "o": "CLIC1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5139354D4639009", "o": "Chloride intracellular channel protein 1" } ], "ideal_answer": [ "CLIC1 is an intracellular chloride ion channel that is localized both to the nucleus and to the cytolasm." ], "concepts": [ "http://www.uniprot.org/uniprot/CLIC1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008104", "http://www.uniprot.org/uniprot/CLIC1_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051234", "http://www.uniprot.org/uniprot/CLIC1_PIG", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051179", "http://www.uniprot.org/uniprot/CLIC1_HUMAN", "http://www.uniprot.org/uniprot/CLIC1_RABIT", "http://www.uniprot.org/uniprot/CLIC1_BOVIN" ], "type": "summary", "id": "53319916d6d3ac6a3400003f", "snippets": [ { "offsetInBeginSection": 611, "offsetInEndSection": 706, "text": "CLIC1 expression was obtained in the cytoplasm and plasma membrane of cells in both cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21055175", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 686, "text": "CLIC1, an intracellular chloride ion channel,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15827065", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 678, "text": "Like NCC27/CLIC1, CLIC3 is predominantly localized in the nucleus ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9880541", "endSection": "abstract" }, { "offsetInBeginSection": 1270, "offsetInEndSection": 1357, "text": "the nuclear localization pattern of CLIC1 was remarkably changed by insulin stimulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15827065", "endSection": "abstract" } ] }, { "body": "List phosphorylation consensus motifs for Casein Kinase 1 (CK1)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8055935", "http://www.ncbi.nlm.nih.gov/pubmed/18239272", "http://www.ncbi.nlm.nih.gov/pubmed/15975091", "http://www.ncbi.nlm.nih.gov/pubmed/12925738", "http://www.ncbi.nlm.nih.gov/pubmed/11781102", "http://www.ncbi.nlm.nih.gov/pubmed/14710188", "http://www.ncbi.nlm.nih.gov/pubmed/18799313" ], "ideal_answer": [ "The most common consensus motifs for CK1 are: pSer-Xaa-Xaa-Ser, K/R-X-K/R-X-X-S/T, SLS and acidic cluster motifs and SerP/ThrP-Xaa-Xaa-Ser/Thr." ], "exact_answer": [ [ "pSer-Xaa-Xaa-Ser" ], [ "K/R-X-K/R-X-X-S/T" ], [ "SLS and acidic cluster motifs" ], [ "SerP/ThrP-Xaa-Xaa-Ser/Thr" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010766", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016310", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042327", "http://www.uniprot.org/uniprot/KC1A_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032921", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016384", "http://www.uniprot.org/uniprot/KC1_PLAF7", "http://www.uniprot.org/uniprot/KC1A_CAEEL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042325", "http://www.uniprot.org/uniprot/KC1A_HUMAN", "http://www.uniprot.org/uniprot/KC1AL_HUMAN" ], "type": "list", "id": "52d832dd98d0239505000003", "snippets": [ { "offsetInBeginSection": 152, "offsetInEndSection": 305, "text": "Members of the protein kinase CK1 family usually phosphorylate residues of serine that are close to other phosphoserine in a consensus motif of pS-X-X-S,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18799313", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 773, "text": "a novel consensus phosphorylation motif (K/R-X-K/R-X-X-S/T) for CK1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18239272", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 299, "text": "CK1 acts as a 'phosphate-directed' kinase whose targeting is primed by a single phosphorylated side chain at position n-3 or n-4 relative to serine/threonine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15975091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The protein kinase CK1 phosphorylates serine residues that are located close to another phosphoserine in the consensus pSer-Xaa-Xaa-Ser.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14710188", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1003, "text": "The results demonstrate that SLS and acidic cluster motifs are crucial for CK1 recognition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12925738", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 750, "text": "The common features include an SLS motif followed two to five residues downstream by a cluster of acidic residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12925738", "endSection": "abstract" }, { "offsetInBeginSection": 1686, "offsetInEndSection": 1832, "text": "These data provide the clear-cut demonstration that the consensus sequence with N-terminal prephosphorylated residue(s), SerP/ThrP-Xaa-Xaa-Ser/Thr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8055935", "endSection": "abstract" } ] }, { "body": "What medication were compared in the ROCKET AF Trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23352688", "http://www.ncbi.nlm.nih.gov/pubmed/22664783", "http://www.ncbi.nlm.nih.gov/pubmed/24659084", "http://www.ncbi.nlm.nih.gov/pubmed/24794785", "http://www.ncbi.nlm.nih.gov/pubmed/24895454", "http://www.ncbi.nlm.nih.gov/pubmed/23869941", "http://www.ncbi.nlm.nih.gov/pubmed/25148838", "http://www.ncbi.nlm.nih.gov/pubmed/23405833", "http://www.ncbi.nlm.nih.gov/pubmed/25083135", "http://www.ncbi.nlm.nih.gov/pubmed/24552831", "http://www.ncbi.nlm.nih.gov/pubmed/25209598", "http://www.ncbi.nlm.nih.gov/pubmed/23954611", "http://www.ncbi.nlm.nih.gov/pubmed/23391196", "http://www.ncbi.nlm.nih.gov/pubmed/24315894", "http://www.ncbi.nlm.nih.gov/pubmed/23500298", "http://www.ncbi.nlm.nih.gov/pubmed/24763930", "http://www.ncbi.nlm.nih.gov/pubmed/24755148", "http://www.ncbi.nlm.nih.gov/pubmed/23030284", "http://www.ncbi.nlm.nih.gov/pubmed/24711702", "http://www.ncbi.nlm.nih.gov/pubmed/25749644" ], "ideal_answer": [ "ROCKET-AF trial compared rivaroxaban and warfarin for for prevention of stroke and embolism." ], "exact_answer": [ [ "rivaroxaban" ], [ "warfarin" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016449", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016032", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986" ], "type": "list", "id": "56bb616dac7ad10019000008", "snippets": [ { "offsetInBeginSection": 241, "offsetInEndSection": 735, "text": "METHODS AND RESULTS: Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25209598", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 895, "text": "This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24711702", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1515, "text": "Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24711702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763930", "endSection": "title" }, { "offsetInBeginSection": 1666, "offsetInEndSection": 1806, "text": "CONCLUSIONS: Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation in relation to the CHADS2 score: a subgroup analysis of the J-ROCKET AF trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954611", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND: Results from a trial of rivaroxaban versus warfarin in 1280 Japanese patients with atrial fibrillation (J-ROCKET AF) revealed that rivaroxaban was noninferior to warfarin with respect to the principal safety outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Rivaroxaban, an oral direct factor Xa-inhibitor was non-inferior to adjusted dose warfarin in the prevention of stroke and embolism among patients with atrial fibrillation (AF) in the ROCKET-AF trial and has been approved for stroke prevention in AF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794785", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 810, "text": "The ROCKET AF trial compared rivaroxaban (20 mg/day; 15 mg/day in patients with creatinine clearance 30-49 ml/min) with dose-adjusted warfarin (international normalized ratio 2-3) in 14,264 patients with AF and a prior history of stroke or at least two other additional risk factors for stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24315894", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763930", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 736, "text": "Different clinical trials have shown the benefits of new oral anticoagulants over warfarin, but patients included in the ROCKET-AF trial were found to be at a higher risk of AF-related complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23405833", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 986, "text": "The ROCKET AF trial demonstrated the noninferiority of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism, with a similar rate of major bleeding and a substantial reduction in intracranial hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Rivaroxaban for stroke prevention in atrial fibrillation: a critical review of the ROCKET AF trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030284", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23500298", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The overall analysis of the rivaroxaban versus warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial revealed that rivaroxaban was not inferior to warfarin with respect to the primary safety outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23352688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Medical costs in the US of clinical events associated with oral anticoagulant (OAC) use compared to warfarin among non-valvular atrial fibrillation patients \u226575 and <75 years of age, based on the ARISTOTLE, RE-LY, and ROCKET-AF trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869941", "endSection": "title" }, { "offsetInBeginSection": 603, "offsetInEndSection": 1061, "text": "In patients at risk of stroke due to atrial fibrillation, rivaroxaban was noninferior compared to warfarin in preventing stroke/systemic embolism in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial and was associated with a similar risk of major bleeding; the incidence of intracranial hemorrhage was 33% lower with rivaroxaban", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24659084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391196", "endSection": "title" }, { "offsetInBeginSection": 87, "offsetInEndSection": 435, "text": "The Phase III ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial showed that rivaroxaban, an oral, direct Factor Xa inhibitor, was noninferior to warfarin for the reduction of stroke or systemic embolism in patients with AF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25083135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25148838", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24895454", "endSection": "title" }, { "offsetInBeginSection": 145, "offsetInEndSection": 392, "text": "The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24895454", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 378, "text": "We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25749644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391196", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24755148", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24895454", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24552831", "endSection": "title" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1275, "text": " Health care providers should consider renal function, concomitant medication, polymorbidity and age prior to prescribing rivaroxaban. Care has to be taken when prescribing rivaroxaban to patients who are different from those included in the ROCKET AF trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794785", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1275, "text": "Health care providers should consider renal function, concomitant medication, polymorbidity and age prior to prescribing rivaroxaban. Care has to be taken when prescribing rivaroxaban to patients who are different from those included in the ROCKET AF trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794785", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 412, "text": "A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF.J-ROCKET AF was a prospective, randomized, double-blind, phase III trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664783", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 412, "text": "A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664783", "endSection": "abstract" } ] }, { "body": "Describe the usefulness of the SPIKE database in human signaling pathways", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "http://www.ncbi.nlm.nih.gov/pubmed/18289391" ], "ideal_answer": [ "The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator\u2019s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015398", "http://amigo.geneontology.org/amigo/term/GO:0007165", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ], "type": "summary", "id": "56bdc452a36a056b3d000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1217, "text": "The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator\u2019s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "SPIKE: a database of highly curated human signaling pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "endSection": "title" }, { "offsetInBeginSection": 553, "offsetInEndSection": 830, "text": "SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "SPIKE--a database, visualization and analysis tool of cellular signaling pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18289391", "endSection": "title" }, { "offsetInBeginSection": 277, "offsetInEndSection": 555, "text": "SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 559, "text": "SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "endSection": "abstract" } ] }, { "body": "Is the Dictyostelium discoideum proteome known?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16875414", "http://www.ncbi.nlm.nih.gov/pubmed/20013782", "http://www.ncbi.nlm.nih.gov/pubmed/20422638", "http://www.ncbi.nlm.nih.gov/pubmed/16957282", "http://www.ncbi.nlm.nih.gov/pubmed/11990506", "http://www.ncbi.nlm.nih.gov/pubmed/16957286", "http://www.ncbi.nlm.nih.gov/pubmed/18820470", "http://www.ncbi.nlm.nih.gov/pubmed/9150929", "http://www.ncbi.nlm.nih.gov/pubmed/22120990" ], "ideal_answer": [ "Yes, The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. Consequently, this genomic sequence information can now be exploited to realize D. discoideum proteomics projects." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004023" ], "type": "yesno", "id": "56b39f148525abca1e000004", "snippets": [ { "offsetInBeginSection": 658, "offsetInEndSection": 1023, "text": "The Negative Proteome Database (NPD) is populated with pair-wise protein sequence comparisons between each of the following proteomes: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Dictyostelium discoideum, Chlamydomonus reinhardti, Escherichia coli K12, Arabidopsis thaliana and Methanoscarcina acetivorans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18820470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The Dictyostelium discoideum proteome--the SWISS-2DPAGE database of the multicellular aggregate (slug).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9150929", "endSection": "title" }, { "offsetInBeginSection": 346, "offsetInEndSection": 461, "text": "Consequently, this genomic sequence information can now be exploited to realize D. discoideum proteomics projects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16957286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16957282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "The 34 Mb genome of Dictyostelium discoideum is carried on 6 chromosomes and has been fully sequenced by an international consortium. The sequence was assembled on the classical and physical maps that had been built up over the years and refined by HAPPY mapping. Annotation of the sequence predicted about 12,000 genes for proteins of at least 50 amino acids in length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16875414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "In this study, a quantitative comparative proteomics approach has been used to analyze the Dictyostelium discoideum mitochondrial proteome variations during vegetative growth, starvation and the early stages of development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20013782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "The secreted proteome profile of developing Dictyostelium discoideum cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20422638", "endSection": "title" }, { "offsetInBeginSection": 764, "offsetInEndSection": 914, "text": "The present repertoire validates our purification method and paves the way for a future proteomics approach to study the dynamics of macropinocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Proteomic analysis of a developmentally regulated secretory vesicle.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11990506", "endSection": "title" } ] }, { "body": "List proteins of lipids droplets", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23204327", "http://www.ncbi.nlm.nih.gov/pubmed/18202123", "http://www.ncbi.nlm.nih.gov/pubmed/21420243", "http://www.ncbi.nlm.nih.gov/pubmed/24036367", "http://www.ncbi.nlm.nih.gov/pubmed/19717842", "http://www.ncbi.nlm.nih.gov/pubmed/19748893", "http://www.ncbi.nlm.nih.gov/pubmed/15731108", "http://www.ncbi.nlm.nih.gov/pubmed/20870251" ], "triples": [ { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "PLIN1_HUMAN" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000B" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000C" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000B", "o": "Perilipin-1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000C", "o": "Lipid droplet-associated protein" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "PLIN_RAT" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834009" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834009", "o": "Lipid droplet-associated protein" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834008", "o": "Perilipin-1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834008" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "PERL_RAT" } ], "ideal_answer": [ "perilipins\nadipose differentiation-related protein\nlipid storage droplet protein 5 \ntail-interacting protein of 47 kilodaltons \nS3-12" ], "exact_answer": [ [ "perilipins" ], [ "adipose differentiation-related protein", "ADFP" ], [ "LSDP5", "lipid storage droplet protein 5" ], [ "tail-interacting protein of 47 kilodaltons", "TIP47" ], [ "S3-12" ] ], "type": "list", "id": "56b3a3ce8525abca1e000005", "snippets": [ { "offsetInBeginSection": 569, "offsetInEndSection": 690, "text": "The perilipins are a multi-protein family that targets lipid droplet surfaces and regulates lipid storage and hydrolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24036367", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1364, "text": "or the abundance of the lipid droplet coat proteins (perilipins 2, 3, 4, and 5) between treatments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "This study investigated the lipid droplet coat proteins perilipin 1 (PLIN1) and perilipin 2 (PLIN2) localization in pig skeletal muscle and their relationship with intramuscular fat (IMF) content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21420243", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 587, "text": "Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilipin A, adipose differentiation-related protein (ADFP), and LSDP5, control lipolysis catalyzed by hormone-sensitive lipase (HSL), a major lipase in adipocytes and several non-adipose cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19717842", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 640, "text": "The coordination of lipid storage and utilization is regulated by the perilipin family of lipid droplet coat proteins [perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), S3-12, tail-interacting protein of 47 kilodaltons (TIP47), and myocardial lipid droplet protein (MLDP)/oxidative tissues-enriched PAT protein (OXPAT)/lipid storage droplet protein 5 (LSDP5)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18202123", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 523, "text": " Perilipin is a member of the evolutionarily related family of PAT proteins (Perilipin, Adipophilin, TIP47), which is defined by sequence similarity and association with lipid droplets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15731108", "endSection": "abstract" } ] }, { "body": "What is the Barr body?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21416650", "http://www.ncbi.nlm.nih.gov/pubmed/17611545", "http://www.ncbi.nlm.nih.gov/pubmed/6270519", "http://www.ncbi.nlm.nih.gov/pubmed/21356720", "http://www.ncbi.nlm.nih.gov/pubmed/7973466", "http://www.ncbi.nlm.nih.gov/pubmed/15682788", "http://www.ncbi.nlm.nih.gov/pubmed/12915472", "http://www.ncbi.nlm.nih.gov/pubmed/16980188", "http://www.ncbi.nlm.nih.gov/pubmed/8978813", "http://www.ncbi.nlm.nih.gov/pubmed/23542155", "http://www.ncbi.nlm.nih.gov/pubmed/10079142", "http://www.ncbi.nlm.nih.gov/pubmed/21811421", "http://www.ncbi.nlm.nih.gov/pubmed/22522168", "http://www.ncbi.nlm.nih.gov/pubmed/10393442" ], "ideal_answer": [ "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). Barr body is an inactivated X chromosome in the normal female somatic cell. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified. ", "The Barr body is the inactive X chromosome in a female somatic cell.", "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). ", "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified. ", "In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. Despite being known for over 50 years, relatively few components of the Barr body have been identified. The Barr body, is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). However, numerous investigators have observed extreme variations in Barr body frequency in tumour cells." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009048", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001740", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900095", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900096", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900097", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012728" ], "type": "summary", "id": "55152c0a46478f2f2c000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21416650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Human inactive X chromosome (Xi) forms a compact structure called the Barr body, which is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23542155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. This discovery offered an important diagnostic technology to the burgeoning clinical science community engaged with the medical interpretation and management of sexual anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16980188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Barr body is an inactivated X chromosome in the normal female somatic cell. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15682788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12915472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6270519", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 315, "text": "However, numerous investigators have observed extreme variations in Barr body frequency in tumour cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6270519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Human inactive X chromosome (Xi) forms a compact structure called the Barr body, which is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23542155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "The Barr body is the inactive X chromosome in a female somatic cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21416650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Barr body is an inactivated X chromosome in the normal female somatic cell. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15682788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16980188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12915472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6270519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "The Barr body is the inactive X chromosome in a female somatic cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21416650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "There are three classical problems at the chromosome level in cytogenetics, namely the formation mechanisms and effects of Barr body, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522168", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 772, "text": ". The fascination arose in part from the realisation that the inactive X corresponded to a dense heterochromatin mass called the \"Barr body\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21811421", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 326, "text": "The presence of a heavily stained condensed chromatin body (i.e., a Barr body) indicates the XX samples. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21356720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Interest has recently reawakened in whether loss of the heterochromatic X chromosome (Barr body) is prevalent in certain breast and ovarian cancers, and new insights into the mechanisms involved have emerged. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17611545", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 583, "text": "The colocalization of a 4,6-diamidino-2-phenylindole dihydrochloride-stained Barr body with one of the two painted X territories allowed the unequivocal discrimination of the inactive X from its active counterpart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8978813", "endSection": "abstract" } ] }, { "body": "Is single-cell analysis (SCA) possible in proteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18392595", "http://www.ncbi.nlm.nih.gov/pubmed/16806894", "http://www.ncbi.nlm.nih.gov/pubmed/16098176", "http://www.ncbi.nlm.nih.gov/pubmed/22203961", "http://www.ncbi.nlm.nih.gov/pubmed/17560583", "http://www.ncbi.nlm.nih.gov/pubmed/20680590", "http://www.ncbi.nlm.nih.gov/pubmed/23445532", "http://www.ncbi.nlm.nih.gov/pubmed/20434785", "http://www.ncbi.nlm.nih.gov/pubmed/21708264", "http://www.ncbi.nlm.nih.gov/pubmed/22468600", "http://www.ncbi.nlm.nih.gov/pubmed/21347466", "http://www.ncbi.nlm.nih.gov/pubmed/15174138", "http://www.ncbi.nlm.nih.gov/pubmed/18664433", "http://www.ncbi.nlm.nih.gov/pubmed/23256674", "http://www.ncbi.nlm.nih.gov/pubmed/18657818", "http://www.ncbi.nlm.nih.gov/pubmed/22921068", "http://www.ncbi.nlm.nih.gov/pubmed/18682362", "http://www.ncbi.nlm.nih.gov/pubmed/22498881", "http://www.ncbi.nlm.nih.gov/pubmed/17109634", "http://www.ncbi.nlm.nih.gov/pubmed/17953400", "http://www.ncbi.nlm.nih.gov/pubmed/17439240" ], "ideal_answer": [ "No, it is not yet feasible, although smaller pilot studies has been performed where a limited number of proteins has been analysed." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005623", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059010" ], "type": "yesno", "id": "5144bc8fd24251bc0500000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Toward Single Cell Analysis by Plume Collimation in Laser Ablation Electrospray Ionization Mass Spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23445532", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 399, "text": "he advent of proteomics and genomics at a single-cell level has set the basis for an outstanding improvement in analytical technology and data acquisition.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23256674", "endSection": "sections.0" }, { "offsetInBeginSection": 613, "offsetInEndSection": 1125, "text": "The new-generation technology of single-cell analysis is able to better characterize a cell's population, identifying and differentiating outlier cells, in order to provide both a single-cell experiment and a corresponding bulk measurement, through the identification, quantification and characterization of all system biology aspects (genomics, transcriptomics, proteomics, metabolomics, degradomics and fluxomics). The movement of omics into single-cell analysis represents a significant and outstanding shift.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23256674", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Laser ablation electrospray ionization (LAESI) is a novel method for the direct imaging of biological tissues by mass spectrometry. By performing ionization in the ambient environment, this technique enables in vivo studies with potential for single-cell analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20680590", "endSection": "sections.0" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1484, "text": "Other approaches for MS-based chemical imaging and profiling include those based on near-field laser ablation and inductively-coupled plasma MS analysis, which offer complementary capabilities for subcellular chemical imaging and profiling.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22498881", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Mass spectrometry imaging and profiling of single cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22498881", "endSection": "title" }, { "offsetInBeginSection": 221, "offsetInEndSection": 560, "text": "his is rapidly changing with the recent examples of single cell genomics, transcriptomics, proteomics and metabolomics. The rate of change is expected to accelerate owing to emerging technologies that range from micro/nanofluidics to microfabricated interfaces for mass spectrometry to third- and fourth-generation automated DNA sequencers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20434785", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Single-cell analysis (SCA) has been increasingly recognized as the key technology for the elucidation of cellular functions, which are not accessible from bulk measurements on the population level. Thus far, SCA has been achieved by miniaturization of established engineering concepts to match the dimensions of a single cell", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22468600", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22203961", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 335, "text": "The amount of single proteins in single cells can be as low as one copy per cell and is for most proteins in the attomole range or below; usually considered as insufficient for proteomic analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21708264", "endSection": "sections.0" }, { "offsetInBeginSection": 517, "offsetInEndSection": 818, "text": "n Arabidopsis thaliana, we have successfully identified nine unique proteins in a single-cell sample and 56 proteins from a pool of 15 single-cell samples from glucosinolate-rich S-cells by nanoLC-MS/MS proteomic analysis, thus establishing the proof-of-concept for true single-cell proteomic analysis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21708264", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "A first step towards practical single cell proteomics: a microfluidic antibody capture chip with TIRF detection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21347466", "endSection": "title" } ] }, { "body": "Is shotgun lipidomics the direct infusion of a lipid sample into a mass spectrometer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17920553", "http://www.ncbi.nlm.nih.gov/pubmed/22629264", "http://www.ncbi.nlm.nih.gov/pubmed/19408941", "http://www.ncbi.nlm.nih.gov/pubmed/22946708", "http://www.ncbi.nlm.nih.gov/pubmed/21207296", "http://www.ncbi.nlm.nih.gov/pubmed/22282095", "http://www.ncbi.nlm.nih.gov/pubmed/23825371", "http://www.ncbi.nlm.nih.gov/pubmed/21755525" ], "ideal_answer": [ "Yes, shotgun lipidomics relies on direct infusion of total lipid extracts into a high-resolution tandem mass spectrometer." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053719", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013057", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007260", "http://www.biosemantics.org/jochem#4269483" ], "type": "yesno", "id": "532f3e08d6d3ac6a34000034", "snippets": [ { "offsetInBeginSection": 70, "offsetInEndSection": 122, "text": "In direct infusion/injection (or shotgun) lipidomics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23825371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "An efficient shotgun lipidomics strategy was established and optimized for fast phospholipid profiling of viscera from three fish species: Lateolabrax japonicas, Ctenopharyngodon idellus, and Carassius auratus. This strategy relies on direct infusion of total lipid extracts into a tandem mass spectrometer without additional separation of the individual molecular species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22946708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Top-down shotgun lipidomics relies on direct infusion of total lipid extracts into a high-resolution tandem mass spectrometer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22282095", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 317, "text": "shotgun lipidomic approaches that use direct infusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21755525", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 341, "text": "direct infusion (shotgun lipidomics) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21207296", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 745, "text": "direct infusion-based shotgun lipidomics approaches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22629264", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 306, "text": "shotgun lipidomics (MDMS-SL) data, which are acquired directly from lipid extracts after direct infusion ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19408941", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 1123, "text": "Through direct infusion of the resultant enriched solution, we identified and quantitated a variety of very-low-abundance sphingolipid classes (e.g., sphingosine, psychosine, and lysosphingomyelin) and molecular species (e.g., sphingomyelin) using electrospray ionization mass spectrometry (i.e., shotgun sphingolipidomics).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17920553", "endSection": "abstract" } ] }, { "body": "How many genes are in the gene signature screened by MammaPrint?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "http://www.ncbi.nlm.nih.gov/pubmed/20094918", "http://www.ncbi.nlm.nih.gov/pubmed/21291290", "http://www.ncbi.nlm.nih.gov/pubmed/19126254", "http://www.ncbi.nlm.nih.gov/pubmed/20359886", "http://www.ncbi.nlm.nih.gov/pubmed/20204499", "http://www.ncbi.nlm.nih.gov/pubmed/21081926", "http://www.ncbi.nlm.nih.gov/pubmed/23347730", "http://www.ncbi.nlm.nih.gov/pubmed/23371464", "http://www.ncbi.nlm.nih.gov/pubmed/21347257", "http://www.ncbi.nlm.nih.gov/pubmed/19214742", "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "http://www.ncbi.nlm.nih.gov/pubmed/21151591", "http://www.ncbi.nlm.nih.gov/pubmed/18483364", "http://www.ncbi.nlm.nih.gov/pubmed/18786252", "http://www.ncbi.nlm.nih.gov/pubmed/22738860" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17680439", "o": "MammaPrint" } ], "ideal_answer": [ "Mammaprint has a 70 gene signature." ], "exact_answer": [ "70 genes" ], "type": "factoid", "id": "514a0f4ad24251bc05000053", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "The 70 gene-signature (MammaPrint(\u00ae)) is a prognostic profile of distant recurrence and survival of primary breast cancer (BC)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23347730", "endSection": "sections.0" }, { "offsetInBeginSection": 501, "offsetInEndSection": 552, "text": "The 70-gene signature was analysed using MammaPrint", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22738860", "endSection": "sections.0" }, { "offsetInBeginSection": 52, "offsetInEndSection": 104, "text": "the prognostic value of the MammaPrint(TM) signature", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "endSection": "sections.0" }, { "offsetInBeginSection": 474, "offsetInEndSection": 498, "text": "by the 70-gene signature", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "endSection": "sections.0" }, { "offsetInBeginSection": 477, "offsetInEndSection": 498, "text": "the 70-gene signature", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "endSection": "sections.0" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1484, "text": "n FDA-cleared 70-gene signature of MammaPrint panel", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "endSection": "sections.0" }, { "offsetInBeginSection": 22, "offsetInEndSection": 50, "text": "70-gene MammaPrint signature", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21291290", "endSection": "title" }, { "offsetInBeginSection": 470, "offsetInEndSection": 487, "text": "70-gene signature", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21291290", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 156, "text": "The 70-gene signature (MammaPrint) is a prognostic test used to guide adjuvant treatment decisions in patients with node-negative breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20359886", "endSection": "sections.0" }, { "offsetInBeginSection": 917, "offsetInEndSection": 935, "text": "70-gene signature.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20359886", "endSection": "sections.0" }, { "offsetInBeginSection": 26, "offsetInEndSection": 43, "text": "70-gene signature", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20359886", "endSection": "title" }, { "offsetInBeginSection": 158, "offsetInEndSection": 220, "text": "the 70-gene MammaPrint signature for chemotherapy (CT) benefit", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20204499", "endSection": "sections.0" }, { "offsetInBeginSection": 61, "offsetInEndSection": 93, "text": "the 70-gene MammaPrint signature", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20094918", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The 70-gene signature (MammaPrint) is a prognostic tool used to guide adjuvant treatment decisions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214742", "endSection": "sections.0" }, { "offsetInBeginSection": 214, "offsetInEndSection": 233, "text": "the 70-gene profile", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214742", "endSection": "sections.0" }, { "offsetInBeginSection": 287, "offsetInEndSection": 373, "text": "the 70-gene prognosis signature (MammaPrint) for node-negative breast cancer patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19126254", "endSection": "sections.0" }, { "offsetInBeginSection": 642, "offsetInEndSection": 660, "text": "70-gene signature.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19126254", "endSection": "sections.0" }, { "offsetInBeginSection": 642, "offsetInEndSection": 659, "text": "70-gene signature", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19126254", "endSection": "sections.0" }, { "offsetInBeginSection": 836, "offsetInEndSection": 868, "text": "The MammaPrint 70-gene signature", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483364", "endSection": "sections.0" } ] }, { "body": "Is apixaban effective for treatment of acute venous thromboembolism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18393142", "http://www.ncbi.nlm.nih.gov/pubmed/22084658", "http://www.ncbi.nlm.nih.gov/pubmed/22153026", "http://www.ncbi.nlm.nih.gov/pubmed/24057162", "http://www.ncbi.nlm.nih.gov/pubmed/23808982", "http://www.ncbi.nlm.nih.gov/pubmed/24554904", "http://www.ncbi.nlm.nih.gov/pubmed/19014462", "http://www.ncbi.nlm.nih.gov/pubmed/22795419", "http://www.ncbi.nlm.nih.gov/pubmed/23233582", "http://www.ncbi.nlm.nih.gov/pubmed/19308891", "http://www.ncbi.nlm.nih.gov/pubmed/23150473", "http://www.ncbi.nlm.nih.gov/pubmed/24278706", "http://www.ncbi.nlm.nih.gov/pubmed/23822763", "http://www.ncbi.nlm.nih.gov/pubmed/23117646" ], "ideal_answer": [ "Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies.", "Yes, apixaban is effective for treatment of acute venous thromboembolismis. Apixiban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013923", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020246", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054556", "http://www.biosemantics.org/jochem#4243936" ], "type": "yesno", "id": "52fc94572059c6d71c000070", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24057162", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1132, "text": "These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24057162", "endSection": "abstract" }, { "offsetInBeginSection": 1718, "offsetInEndSection": 1898, "text": "A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23808982", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 186, "text": "To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150473", "endSection": "abstract" }, { "offsetInBeginSection": 2087, "offsetInEndSection": 2308, "text": "ompared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150473", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 329, "text": "Nowadays, the new anticoagulants, such as dabigatran, rivaroxaban and apixaban, show potential advantages over classical treatments. These agents inhibit specific coagulation factors and are administered orally at fixed doses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23117646", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1308, "text": "In a recently completed phase III trial, apixaban also demonstrated promising efficacy and safety in that indication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795419", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 419, "text": "the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18393142", "endSection": "abstract" } ] }, { "body": "Is the tricarboxylic acid (TCA) cycle affected in inflammation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23776651", "http://www.ncbi.nlm.nih.gov/pubmed/24727425", "http://www.ncbi.nlm.nih.gov/pubmed/21523508", "http://www.ncbi.nlm.nih.gov/pubmed/24361092", "http://www.ncbi.nlm.nih.gov/pubmed/21287666", "http://www.ncbi.nlm.nih.gov/pubmed/25461442", "http://www.ncbi.nlm.nih.gov/pubmed/24086109", "http://www.ncbi.nlm.nih.gov/pubmed/25686106", "http://www.ncbi.nlm.nih.gov/pubmed/25798621", "http://www.ncbi.nlm.nih.gov/pubmed/18383346" ], "ideal_answer": [ "Metabolic reprogramming is implicated in macrophage activation. In many cases, intermediates of the TCA cycle are involved in the response to hypoxic conditions brought about by inflammation." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007249", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002952", "http://amigo.geneontology.org/amigo/term/GO:0006099" ], "type": "yesno", "id": "56c4a217b04e159d0e000001", "snippets": [ { "offsetInBeginSection": 210, "offsetInEndSection": 555, "text": "In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21523508", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1290, "text": "Our study raises the possibility that GC/MS-based profiling of amino acids and TCA cycle-related molecules is a useful early diagnostic tool for UC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21523508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24361092", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1025, "text": "In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23776651", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 804, "text": "Thus, IL-1beta+TNFalpha treated astrocytes show a marked decrease in glycogen levels, a slight but not significant decrease in lactate release as well as a massive increase in both the pentose phosphate pathway and TCA cycle activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18383346", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 879, "text": "A total of 77 and 92 metabolites were detected in serum and colon tissue, respectively, and among the metabolites the compositions of TCA cycle intermediates and amino acids changed depending on the degree of colitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21287666", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1119, "text": "Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086109", "endSection": "abstract" }, { "offsetInBeginSection": 1756, "offsetInEndSection": 2006, "text": "These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086109", "endSection": "abstract" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1570, "text": "These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24727425", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 910, "text": "The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24727425", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1711, "text": "Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25461442", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 814, "text": "Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25798621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Metabolic reprogramming is implicated in macrophage activation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25798621", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1526, "text": "BHB blocks the NLRP3 inflammasome without undergoing oxidation in the TCA cycle, and independently of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydrocaboxylic acid receptor 2 (HCAR2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25686106", "endSection": "abstract" }, { "offsetInBeginSection": 1865, "offsetInEndSection": 2030, "text": "Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25686106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Succinate: a metabolic signal in inflammation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24361092", "endSection": "title" } ] }, { "body": "What are the indications for treatment with anti-hepcidin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24231125", "http://www.ncbi.nlm.nih.gov/pubmed/24175256", "http://www.ncbi.nlm.nih.gov/pubmed/24159166" ], "ideal_answer": [ "improving anemia control\nanemia management in hemodialysis\niron-restricted anemias" ], "exact_answer": [ [ "iron-restricted anemias" ], [ "anemia of inflammation" ], [ "anemia of cancer" ], [ "anemia of chronic kidney disease" ], [ "anemia of chronic disease" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064451" ], "type": "list", "id": "535d59349a4572de6f000009", "snippets": [ { "offsetInBeginSection": 694, "offsetInEndSection": 748, "text": "anti-hepcidin strategies for improving anemia control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231125", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1228, "text": "anti-hepcidin therapies may improve anemia management in hemodialysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24175256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Anti-hepcidin therapy for iron-restricted anemias", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24159166", "endSection": "title" }, { "offsetInBeginSection": 73, "offsetInEndSection": 219, "text": "human anti-hepcidin antibody as a novel therapeutic for iron-restricted anemias such as anemia of inflammation, cancer, or chronic kidney disease ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24159166", "endSection": "abstract" } ] }, { "body": "How many genera comprise the Flaviviridae family?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21249176", "http://www.ncbi.nlm.nih.gov/pubmed/19555498", "http://www.ncbi.nlm.nih.gov/pubmed/19035566", "http://www.ncbi.nlm.nih.gov/pubmed/16225688", "http://www.ncbi.nlm.nih.gov/pubmed/8396675", "http://www.ncbi.nlm.nih.gov/pubmed/18991746", "http://www.ncbi.nlm.nih.gov/pubmed/22039536", "http://www.ncbi.nlm.nih.gov/pubmed/20470249", "http://www.ncbi.nlm.nih.gov/pubmed/19534676", "http://www.ncbi.nlm.nih.gov/pubmed/22513121", "http://www.ncbi.nlm.nih.gov/pubmed/22031952" ], "ideal_answer": [ "The family Flaviviridae is comprised of three genera: Flavivirus, Pestivirus and Hepacivirus." ], "exact_answer": [ "three", "3" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018067" ], "type": "factoid", "id": "51651e24298dcd4e51000054", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "Within a project aimed at discovering new Flaviviridae inhibitors, new variously substituted 2-phenylbenzimidazoles were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against viruses representatives of the three genera of the Flaviviridae family, i.e.: Pestivirus (BVDV), Flavivirus (YFV) and Hepacivirus (HCV).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513121", "endSection": "sections.0" }, { "offsetInBeginSection": 172, "offsetInEndSection": 340, "text": "Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Pestiviruses and Flaviviruses;", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20470249", "endSection": "sections.0" }, { "offsetInBeginSection": 189, "offsetInEndSection": 368, "text": "The RNA-stimulated NTPase activity of this protein from prototypic members of the Pestivirus and Flavivirus genera has recently been established and enzymologically characterized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8396675", "endSection": "sections.0" }, { "offsetInBeginSection": 196, "offsetInEndSection": 539, "text": "Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19534676", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 490, "text": "Forty-three 2-[(benzotriazol-1/2-yl)methyl]benzimidazoles, bearing either linear (dialkylamino)alkyl- or bulkier (quinolizidin-1-yl)alkyl moieties at position 1, were evaluated in cell-based assays for cytotoxicity and antiviral activity against viruses representative of two of the three genera of the Flaviviridae family, i.e. Flaviviruses (Yellow Fever Virus (YFV)) and Pestiviruses (Bovine Viral Diarrhoea Virus (BVDV)), as Hepaciviruses can hardly be used in routine cell-based assays.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19035566", "endSection": "sections.0" }, { "offsetInBeginSection": 360, "offsetInEndSection": 703, "text": "Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991746", "endSection": "sections.0" }, { "offsetInBeginSection": 292, "offsetInEndSection": 352, "text": ": Pestivirus (BVDV), Flavivirus (YFV) and Hepacivirus (HCV).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513121", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The family Flaviviridae contains three genera of positive-strand RNA viruses, namely, Flavivirus, Hepacivirus (e.g., hepatitis C virus [HCV]), and Pestivirus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22031952", "endSection": "sections.0" } ] }, { "body": "Are reduced-nicotine cigarettes effective for smoking cessation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26422724", "http://www.ncbi.nlm.nih.gov/pubmed/25150282", "http://www.ncbi.nlm.nih.gov/pubmed/21232155", "http://www.ncbi.nlm.nih.gov/pubmed/25025523", "http://www.ncbi.nlm.nih.gov/pubmed/24746485", "http://www.ncbi.nlm.nih.gov/pubmed/17573781", "http://www.ncbi.nlm.nih.gov/pubmed/23603206", "http://www.ncbi.nlm.nih.gov/pubmed/16497603", "http://www.ncbi.nlm.nih.gov/pubmed/18629723", "http://www.ncbi.nlm.nih.gov/pubmed/19793786", "http://www.ncbi.nlm.nih.gov/pubmed/20078491" ], "ideal_answer": [ "Yes, reduced-nicotine cigarettes are effective for smoking cessation." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016540" ], "type": "yesno", "id": "56bc8d65ac7ad1001900001a", "snippets": [ { "offsetInBeginSection": 1812, "offsetInEndSection": 1989, "text": "CONCLUSIONS: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26422724", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1037, "text": "RESULTS: Significant reductions in nicotine intake were observed between usual brand smoking (\u223c1.2 mg nicotine) and the 0.3 and 0.05 mg nicotine emission cigarettes, but not the 0.6 mg cigarette.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25150282", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1526, "text": "CONCLUSIONS: The study adds to the evidence that cigarettes with markedly reduced nicotine content are not associated with increased smoking intensity or exposure to smoke toxicants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25150282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "BACKGROUND: When switching from usual brand cigarettes, very low nicotine content (VLNC) cigarettes lead to a reduction in the number of cigarettes smoked, toxicant exposure, withdrawal symptoms and dependence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24746485", "endSection": "abstract" }, { "offsetInBeginSection": 1623, "offsetInEndSection": 1927, "text": "Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16497603", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1358, "text": "Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18629723", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1620, "text": "Quest plus NRT offers promise as a new smoking cessation treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18629723", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 932, "text": "We identified three clinical trials (total n = 489) that suggest that smokers can dissociate nicotine delivery from the act of smoking if they use reduced-nicotine content cigarettes in combination with nicotine replacement therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793786", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1250, "text": "CONCLUSION: The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20078491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17573781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603206", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 739, "text": "Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21232155", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 878, "text": "The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18629723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17573781", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 406, "text": "Specifically, standards that required substantially reduced nicotine content in cigarettes could enable cessation in smokers and prevent future smoking among current non-smokers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25025523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603206", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 499, "text": "Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21232155", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 567, "text": "The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18629723", "endSection": "abstract" }, { "offsetInBeginSection": 1480, "offsetInEndSection": 1927, "text": "These results suggest that use of NRT before a target quit-smoking date deserves further evaluation as a possible smoking cessation treatment. Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16497603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17573781", "endSection": "abstract" } ] }, { "body": "Is the Wnt protein modified by notum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18505598", "http://www.ncbi.nlm.nih.gov/pubmed/22669824", "http://www.ncbi.nlm.nih.gov/pubmed/22159580", "http://www.ncbi.nlm.nih.gov/pubmed/18429952", "http://www.ncbi.nlm.nih.gov/pubmed/24523458", "http://www.ncbi.nlm.nih.gov/pubmed/15647319", "http://www.ncbi.nlm.nih.gov/pubmed/25731175", "http://www.ncbi.nlm.nih.gov/pubmed/10049571", "http://www.ncbi.nlm.nih.gov/pubmed/24992682" ], "ideal_answer": [ "Yes, \tNotum deacylates Wnt proteins to suppress signalling activity." ], "exact_answer": "yes", "type": "yesno", "id": "57089865cf1c32585100000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Notum deacylates Wnt proteins to suppress signalling activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731175", "endSection": "title" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1089, "text": "Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731175", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 817, "text": "the Wnt inhibitor notum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24992682", "endSection": "abstract" }, { "offsetInBeginSection": 929, "offsetInEndSection": 953, "text": "the WNT-inhibitor notum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523458", "endSection": "abstract" } ] }, { "body": "List functions that are evaluated with the Full Outline of Unresponsiveness score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24556655", "http://www.ncbi.nlm.nih.gov/pubmed/19648386", "http://www.ncbi.nlm.nih.gov/pubmed/24013867", "http://www.ncbi.nlm.nih.gov/pubmed/20551672" ], "ideal_answer": [ "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration." ], "exact_answer": [ [ "eye responses" ], [ "motor responses" ], [ "brainstem reflexes" ], [ "respiration" ] ], "type": "list", "id": "56c1d84cef6e394741000031", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The Full Outline of UnResponsiveness (FOUR) Score is a coma scale that consists of four components (eye and motor response, brainstem reflexes, and respiration). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24556655", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 585, "text": "Recently, the full outline of unresponsiveness (FOUR) score was introduced, which is composed of four clinically distinct categories of evaluation: eye reaction, motor function, brainstem reflexes and respiratory pattern. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013867", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 346, "text": "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20551672", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 485, "text": "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20551672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "To evaluate the validity of the FOUR (Full Outline of UnResponsiveness) score (ranging from 0 to 16), a new coma scale consisting of 4 components (eye response, motor response, brainstem reflexes, and respiration pattern), when used by the staff members of a medical intensive care unit (ICU).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19648386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "To evaluate the validity of the FOUR (Full Outline of UnResponsiveness) score (ranging from 0 to 16), a new coma scale consisting of 4 components (eye response, motor response, brainstem reflexes, and respiration pattern), when used by the staff members of a medical intensive care unit (ICU).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19648386", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 573, "text": "Recently, the full outline of unresponsiveness (FOUR) score was introduced, which is composed of four clinically distinct categories of evaluation: eye reaction, motor function, brainstem reflexes and respiratory pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013867", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 334, "text": "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20551672", "endSection": "abstract" } ] }, { "body": "For the constructions of which organs has 3D printing been tested?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23822094", "http://www.ncbi.nlm.nih.gov/pubmed/12740943", "http://www.ncbi.nlm.nih.gov/pubmed/25281749", "http://www.ncbi.nlm.nih.gov/pubmed/12679063", "http://www.ncbi.nlm.nih.gov/pubmed/25641220", "http://www.ncbi.nlm.nih.gov/pubmed/25839977", "http://www.ncbi.nlm.nih.gov/pubmed/2087655", "http://www.ncbi.nlm.nih.gov/pubmed/23635097", "http://www.ncbi.nlm.nih.gov/pubmed/25159591", "http://www.ncbi.nlm.nih.gov/pubmed/23172542", "http://www.ncbi.nlm.nih.gov/pubmed/19901446", "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "http://www.ncbi.nlm.nih.gov/pubmed/25492194", "http://www.ncbi.nlm.nih.gov/pubmed/24805923", "http://www.ncbi.nlm.nih.gov/pubmed/25197745", "http://www.ncbi.nlm.nih.gov/pubmed/24288392", "http://www.ncbi.nlm.nih.gov/pubmed/22436025", "http://www.ncbi.nlm.nih.gov/pubmed/25387454", "http://www.ncbi.nlm.nih.gov/pubmed/24942232", "http://www.ncbi.nlm.nih.gov/pubmed/25691496", "http://www.ncbi.nlm.nih.gov/pubmed/25866560", "http://www.ncbi.nlm.nih.gov/pubmed/18154465" ], "ideal_answer": [ "Nose, ear and meniscus prototypes/constructs have been produced with 3D (3-dimesional) printing." ], "exact_answer": [ [ "nose" ], [ "ear" ], [ "meniscus" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D066330", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011327" ], "type": "list", "id": "5713bf261174fb1755000011", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 245, "text": "To determine the potential of an integrated, image-based computer-aided design (CAD) and 3-dimensional (3D) printing approach to engineer scaffolds for head and neck cartilaginous reconstruction for auricular and nasal reconstruction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25281749", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 867, "text": "Subcutaneous in vivo implantation of auricular and nasal scaffolds was performed in a porcine model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25281749", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1616, "text": "Auricular and nasal constructs with several types of microporous architecture were rapidly manufactured with high fidelity to human patient anatomy. Subcutaneous in vivo implantation of auricular and nasal scaffolds resulted in an excellent appearance and complete soft tissue ingrowth. Histological analysis of in vitro scaffolds demonstrated native-appearing cartilaginous growth that respected the boundaries of the scaffold.CONCLUSION: Integrated, image-based CAD and 3D printing processes generated patient-specific nasal and auricular scaffolds that supported cartilage regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25281749", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 929, "text": "A prototype meniscus cartilage was prepared to illustrate the potential application in bioengineering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25197745", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 1148, "text": "As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23635097", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1598, "text": "In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23172542", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 864, "text": "Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25866560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25866560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "3D printing of HEK 293FT cell-laden hydrogel into macroporous constructs with high cell viability and normal biological functions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25691496", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "3D-printing of lightweight cellular composites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24942232", "endSection": "title" }, { "offsetInBeginSection": 329, "offsetInEndSection": 459, "text": "3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 355, "text": "In this paper, we reported a novel study of 3D printing of cell lines derived from human embryonic kidney tissue into a macroporous tissue-like construct. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25691496", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 731, "text": "Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 509, "text": "Organ printing, which we define as computer-aided, jet-based 3D tissue-engineering of living human organs, offers a possible solution. Organ printing involves three sequential steps: pre-processing or development of \"blueprints\" for organs; processing or actual organ printing; and postprocessing or organ conditioning and accelerated organ maturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12679063", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 509, "text": "Organ printing involves three sequential steps: pre-processing or development of \"blueprints\" for organs; processing or actual organ printing; and postprocessing or organ conditioning and accelerated organ maturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12679063", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 633, "text": "Bioprinting has no or little side effect to the printed mammalian cells and it can conveniently combine with gene transfection or drug delivery to the ejected living systems during the precise placement for tissue construction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22436025", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 731, "text": "Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Innovations in 3D printing: a 3D overview from optics to organs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24288392", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Organ printing: computer-aided jet-based 3D tissue engineering.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12679063", "endSection": "title" } ] }, { "body": "Is ospemifene effective for treatment of dyspareunia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24055829", "http://www.ncbi.nlm.nih.gov/pubmed/24075094", "http://www.ncbi.nlm.nih.gov/pubmed/23985562", "http://www.ncbi.nlm.nih.gov/pubmed/23605694", "http://www.ncbi.nlm.nih.gov/pubmed/23945733", "http://www.ncbi.nlm.nih.gov/pubmed/20429673", "http://www.ncbi.nlm.nih.gov/pubmed/20032798", "http://www.ncbi.nlm.nih.gov/pubmed/24109197", "http://www.ncbi.nlm.nih.gov/pubmed/23361170", "http://www.ncbi.nlm.nih.gov/pubmed/23777900", "http://www.ncbi.nlm.nih.gov/pubmed/24251418" ], "ideal_answer": [ "Yes, ospamifene is effective for treatment of dyspareunia. Ospemifene is a selective estrogen receptor modulator, or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women. Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.biosemantics.org/jochem#4226329", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004414" ], "type": "yesno", "id": "5335b373d6d3ac6a34000050", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 175, "text": "Ospemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251418", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1554, "text": "For the comparison of short-term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD]\u2009=\u2009-37.5, 95% confidence interval [CI]\u2009=\u2009-41.83 to -33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD =\u2009-0.89, 95% CI =\u2009-0.98 to -0.80, P = 0.00001), and dyspareunia (SMD =\u2009-0.37, 95% CI =\u2009-0.43 to -0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251418", "endSection": "abstract" }, { "offsetInBeginSection": 1841, "offsetInEndSection": 1998, "text": "This meta-analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251418", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 325, "text": "Ospemifene is a selective estrogen receptor modulator (SERM), or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24109197", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1190, "text": "In conclusion, ospemifene is a SERM with a unique estrogen agonist/antagonist tissue profile that was recently approved in the US for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24109197", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 334, "text": "To characterize the pharmacokinetics of the oral, non-estrogen agent ospemifene, an estrogen agonist/antagonist with tissue-selective effects (also called a selective estrogen receptor modulator) that was recently approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075094", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 647, "text": "Here, we review the estrogen agonist/antagonist profile of ospemifene, a novel triphenylethylene derivative recently approved to treat dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause, both preclinically and clinically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055829", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1348, "text": " Long-term studies on the endometrial safety of local estrogen and ospemifene are lacking. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23985562", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 590, "text": "Ospemifene is a tissue-selective estrogen agonist/antagonist (a selective estrogen receptor modulator) recently approved by the US Food and Drug Administration for treatment of dyspareunia, a symptom of VVA, due to menopause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945733", "endSection": "abstract" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1662, "text": "SERMs with positive vaginal effects (such as improvement in the vaginal maturation index, reduced vaginal pH, and improvement in the signs and symptoms of VVA) on postmenopausal symptomatic women include lasofoxifene (clinical development on hold) and ospemifene, which was recently approved for the treatment of VVA-related dyspareunia, with a class effect warning of potential venous thrombosis risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777900", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 446, "text": "Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23605694", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 729, "text": "This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23605694", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 258, "text": "The aim of this work was to study the role of ospemifene, a novel selective estrogen receptor modulator, in the treatment of vulvar and vaginal atrophy in postmenopausal women with moderate to severe dyspareunia and physiological vaginal changes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23361170", "endSection": "abstract" }, { "offsetInBeginSection": 1677, "offsetInEndSection": 1828, "text": "In this study, once-daily oral ospemifene 60 mg was effective for the treatment of vulvar and vaginal atrophy in postmenopausal women with dyspareunia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23361170", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1367, "text": "Clinical trials have confirmed that daily doses are well-tolerated and that it is effective in normalizing vaginal maturation index and pH as well as improving the symptoms associated with VVA including dyspareunia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20429673", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1521, "text": "Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20032798", "endSection": "abstract" } ] }, { "body": "Is pregabalin effective for treatment of patients with restless leg syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23859128", "http://www.ncbi.nlm.nih.gov/pubmed/22851801", "http://www.ncbi.nlm.nih.gov/pubmed/18656214", "http://www.ncbi.nlm.nih.gov/pubmed/24521108", "http://www.ncbi.nlm.nih.gov/pubmed/17489946", "http://www.ncbi.nlm.nih.gov/pubmed/23746768", "http://www.ncbi.nlm.nih.gov/pubmed/24363103", "http://www.ncbi.nlm.nih.gov/pubmed/23385700", "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "http://www.ncbi.nlm.nih.gov/pubmed/24119681", "http://www.ncbi.nlm.nih.gov/pubmed/23304742", "http://www.ncbi.nlm.nih.gov/pubmed/20466589", "http://www.ncbi.nlm.nih.gov/pubmed/24899755", "http://www.ncbi.nlm.nih.gov/pubmed/22570552", "http://www.ncbi.nlm.nih.gov/pubmed/20427750", "http://www.ncbi.nlm.nih.gov/pubmed/23771546", "http://www.ncbi.nlm.nih.gov/pubmed/23703310", "http://www.ncbi.nlm.nih.gov/pubmed/23524988" ], "ideal_answer": [ "Yes, numerous evidence from clinical trials indicate that pregabalic is effective for treatment of patients diagnosed with restless leg syndrome." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4236113" ], "type": "yesno", "id": "54cf4a0ef693c3b16b00000c", "snippets": [ { "offsetInBeginSection": 1504, "offsetInEndSection": 1784, "text": "CONCLUSIONS: This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24899755", "endSection": "abstract" }, { "offsetInBeginSection": 2175, "offsetInEndSection": 2372, "text": "CONCLUSIONS: Pregabalin provided significantly improved treatment outcomes as compared with placebo, and augmentation rates were significantly lower with pregabalin than with 0.5 mg of pramipexole.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24521108", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1318, "text": "The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24363103", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 905, "text": "Pregabalin has been established as effective for up to 1 year in treating RLS/WED (Level A evidence). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859128", "endSection": "abstract" }, { "offsetInBeginSection": 2827, "offsetInEndSection": 2982, "text": "In the group of anticonvulsants, only the trials performed with \u03b1\u2082\u03b4 ligands such as gabapentin, gabapentin enacarbil, and pregabalin showed good efficacy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746768", "endSection": "abstract" }, { "offsetInBeginSection": 1395, "offsetInEndSection": 1619, "text": "Alternative or additional pharmacologic treatment with a lower level of overall quality of evidence includes opioids (codeine, tramadol, and oxycodone) and anticonvulsants (gabapentin, gabapentin enacarbil, and pregabalin). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23703310", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 1116, "text": "There is sufficient evidence to conclude that dopamine agonists such as rotigotine transdermal patch, pramipexole, ropinirole, gabapentin enacarbil, pregabalin and gabapentin are effective in the short-term treatment of RLS and rotigotine, followed by gabapentin enacarbil, ropinirole, pramipexole and gabapentin for long-term treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23524988", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 818, "text": "Calcium channel alpha-2-delta ligands (gabapentin, gabapentin enacarbil, and pregabalin) provide alternative therapies for RLS especially in patients with augmentation, impulse control disorders, or hypersomnia induced by dopamine agonists. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385700", "endSection": "abstract" }, { "offsetInBeginSection": 2129, "offsetInEndSection": 2381, "text": "Alpha-2-delta ligands (gabapentin enacarbil, gabapentin, and pregabalin) increased the number of IRLS responders (RR=1.66; [95% CI: 1.33 to 2.09], k=3, high strength of evidence) and mean change in IRLS symptom scores (k=3, high strength of evidence). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23304742", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1408, "text": "RECOMMENDATIONS: Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short-term treatment for RLS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 810, "text": "Therapies with an OPTION level of recommendation include carbamazepine, gabapentin, pregabalin, clonidine, and for patients with low ferritin levels, iron supplementation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22851801", "endSection": "abstract" }, { "offsetInBeginSection": 1439, "offsetInEndSection": 1565, "text": "CONCLUSIONS: In this 6-week phase 2b study, pregabalin reduced RLS symptoms in patients with moderate-to-severe idiopathic RLS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20466589", "endSection": "abstract" }, { "offsetInBeginSection": 1974, "offsetInEndSection": 2206, "text": "CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20427750", "endSection": "abstract" }, { "offsetInBeginSection": 2493, "offsetInEndSection": 2634, "text": "In severe, refractory or neuropathy-associated RLS, antiepileptic (gabapentin, pregabalin) or opioid (oxycodone, tramadol) drugs can be used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18656214", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1315, "text": "The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24363103", "endSection": "abstract" }, { "offsetInBeginSection": 1935, "offsetInEndSection": 2139, "text": "This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20427750", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1360, "text": "Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short-term treatment for RLS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "endSection": "abstract" } ] }, { "body": "What is the biological role of expansins in fungi?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15195944", "http://www.ncbi.nlm.nih.gov/pubmed/18400936", "http://www.ncbi.nlm.nih.gov/pubmed/20478643", "http://www.ncbi.nlm.nih.gov/pubmed/18406638", "http://www.ncbi.nlm.nih.gov/pubmed/15605243", "http://www.ncbi.nlm.nih.gov/pubmed/19479322" ], "ideal_answer": [ "Expansins are extracellular proteins that increase plant cell-wall extensibility. These wall-loosening proteins are involved in cell wall extension and polysaccharide degradation. In fungi expansins and expansin-like proteins have been found to localize in the conidial cell wall and are probably involved in cell wall remodeling during germination." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005658" ], "type": "summary", "id": "513eec89bee46bd34c00000d", "snippets": [ { "offsetInBeginSection": 88, "offsetInEndSection": 174, "text": "interactions with alpha-expansin in cell wall extension and polysaccharide degradation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20478643", "endSection": "sections.0" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1524, "text": "cell wall swelling may not be a significant event during the action of expansin and hydrolases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20478643", "endSection": "sections.0" }, { "offsetInBeginSection": 442, "offsetInEndSection": 585, "text": "To evaluate a putative implication of three newly identified expansin/family 45 endoglucanase-like (EEL) proteins in lignocellulose degradation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19479322", "endSection": "sections.0" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1232, "text": "Our results show that EglD is a conidial cell wall localized expansin-like protein, which could be involved in cell wall remodeling during germination", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18406638", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Swollenin, a protein first characterized in the saprophytic fungus Trichoderma reesei, contains an N-terminal carbohydrate-binding module family 1 domain (CBD) with cellulose-binding function and a C-terminal expansin-like domain", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18400936", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "alpha-Expansins are extracellular proteins that increase plant cell-wall extensibility", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15605243", "endSection": "sections.0" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1561, "text": "these wall-loosening proteins are directly involved in the accommodation of the fungus by infected cortical cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15605243", "endSection": "sections.0" } ] }, { "body": "Can zinc finger nucleases be used to combat disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24223114", "http://www.ncbi.nlm.nih.gov/pubmed/15806097", "http://www.ncbi.nlm.nih.gov/pubmed/22318089", "http://www.ncbi.nlm.nih.gov/pubmed/20389291", "http://www.ncbi.nlm.nih.gov/pubmed/18511461", "http://www.ncbi.nlm.nih.gov/pubmed/23161061", "http://www.ncbi.nlm.nih.gov/pubmed/16082368", "http://www.ncbi.nlm.nih.gov/pubmed/21411759", "http://www.ncbi.nlm.nih.gov/pubmed/20846404", "http://www.ncbi.nlm.nih.gov/pubmed/21631241", "http://www.ncbi.nlm.nih.gov/pubmed/20594338", "http://www.ncbi.nlm.nih.gov/pubmed/24557916", "http://www.ncbi.nlm.nih.gov/pubmed/24808958", "http://www.ncbi.nlm.nih.gov/pubmed/23451191" ], "ideal_answer": [ "Yes, zinc finger nucleases are a useful tool for treating disease." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016335", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015032", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.disease-ontology.org/api/metadata/DOID:4" ], "type": "yesno", "id": "56f15c5a2ac5ed1459000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Genetic engineering has emerged as a powerful mechanism for understanding biological systems and a potential approach for redressing congenital disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318089", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1227, "text": "This is of particular importance, given the momentum currently behind ZFNs in moving into phase I clinical trials. This study provides a historical account of the origins of ZFN technology, an analysis of current techniques and applications, and an examination of the ethical issues applicable to translational ZFN genetic engineering in early phase clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318089", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 830, "text": "This broad range of tractable species renders ZFNs a useful tool for improving the understanding of complex physiological systems, to produce transgenic animals, cell lines, and plants, and to treat human disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161061", "endSection": "abstract" }, { "offsetInBeginSection": 1262, "offsetInEndSection": 1417, "text": "We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15806097", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Using engineered nucleases, such as Zinc Finger Nucleases (ZFNs) or Transcription Activator-Like Effector Nucleases (TALENs), to make targeted genomic modifications has become a common technique to create new model organisms and custom cell lines, and has shown great promise for disease treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24557916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Zinc Finger nucleases (ZFNs) have been used to create precise genome modifications at frequencies that might be therapeutically useful in gene therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20389291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Zinc finger nucleases as tools to understand and treat human diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20594338", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Evaluation of novel design strategies for developing zinc finger nucleases tools for treating human diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24808958", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "An over expression APP model for anti-Alzheimer disease drug screening created by zinc finger nuclease technology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24223114", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21411759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Recently, it has been shown that targeted mutagenesis using zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) can be used to generate knockout zebrafish lines for analysis of their function and/or developing disease models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23451191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Using engineered nucleases, such as Zinc Finger Nucleases (ZFNs) or Transcription Activator-Like Effector Nucleases (TALENs), to make targeted genomic modifications has become a common technique to create new model organisms and custom cell lines, and has shown great promise for disease treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24557916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Gene correction by homologous recombination with zinc finger nucleases in primary cells from a mouse model of a generic recessive genetic disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20389291", "endSection": "title" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1268, "text": "raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15806097", "endSection": "abstract" } ] }, { "body": "What is known about depression in acoustic neuroma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17711494", "http://www.ncbi.nlm.nih.gov/pubmed/8965089", "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "http://www.ncbi.nlm.nih.gov/pubmed/2775668" ], "ideal_answer": [ "From 10.2% to 38% acoustic neuroma patients report depression. Depression is predicted by the number of symptoms, prolonged postoperative headache, deterioration of hearing and female gender." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:12689", "http://www.disease-ontology.org/api/metadata/DOID:1596", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009464" ], "type": "summary", "id": "56bb54d3ac7ad10019000006", "snippets": [ { "offsetInBeginSection": 710, "offsetInEndSection": 805, "text": "Clinically significant anxiety was reported by 29.8% of participants and 10.2% were depressed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1124, "text": "Time since management, number of symptoms and comorbid medical conditions predicted anxiety, while depression was predicted by number of symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 864, "text": "Depression (usually mild) occurred in 24% of the respondents, being significantly more common in prolonged postoperative headache patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17711494", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 681, "text": "Three patients had a depressive disorder in the preoperative assessment. Of the remaining 24 patients, nine (38%) had a depressive disorder at the three month check up. Deterioration of hearing was the only postoperative detriment associated with a depressive disorder (P = 0\u00b7024). All nine patients with a depressive disorder were women (P = 0\u00b7001), giving them a 69% incidence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8965089", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1091, "text": "Content analysis indicated that the majority of subjects experienced tiredness, depression, headache, and dryness of eyes and mouth in the postoperative and convalescent phases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2775668", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1587, "text": "Treating physicians should be aware that as the number of acoustic neuroma symptoms increases, so may the likelihood of clinically significant anxiety and depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1430, "text": "Treating physicians should be aware that as the number of acoustic neuroma symptoms increases, so may the likelihood of clinically significant anxiety and depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 804, "text": "Clinically significant anxiety was reported by 29.8% of participants and 10.2% were depressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1123, "text": "Time since management, number of symptoms and comorbid medical conditions predicted anxiety, while depression was predicted by number of symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1431, "text": "This appears to be the first study among acoustic neuroma patients in which anxiety and depression were compared across management options. Treating physicians should be aware that as the number of acoustic neuroma symptoms increases, so may the likelihood of clinically significant anxiety and depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1264, "text": "Time since management, number of symptoms and comorbid medical conditions predicted anxiety, while depression was predicted by number of symptoms. This appears to be the first study among acoustic neuroma patients in which anxiety and depression were compared across management options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "endSection": "abstract" } ] }, { "body": "Mutation of which gene is associated with Achondroplasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10932008", "http://www.ncbi.nlm.nih.gov/pubmed/10881785", "http://www.ncbi.nlm.nih.gov/pubmed/9115628", "http://www.ncbi.nlm.nih.gov/pubmed/7702086", "http://www.ncbi.nlm.nih.gov/pubmed/9949234", "http://www.ncbi.nlm.nih.gov/pubmed/15221641", "http://www.ncbi.nlm.nih.gov/pubmed/20301331", "http://www.ncbi.nlm.nih.gov/pubmed/12048679", "http://www.ncbi.nlm.nih.gov/pubmed/21225389" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1308", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/ACH" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/ACH", "o": "ACH" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1308", "o": "Achondroplasia, 100800" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1308", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/FGFR3" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/FGFR3", "o": "FGFR3" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/FGFR3", "o": "http://www.dbpedia.org/resource/FGFR3" }, { "p": 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These phenotypic findings were later confirmed by the presence of fibroblast growth factor receptor 3 (FGFR3) gene mutation N540K.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21225389", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 819, "text": "Achondroplasia can be diagnosed by characteristic clinical and radiographic findings in most affected individuals. In individuals who may be too young to diagnose with certainty or in individuals with atypical findings, molecular genetic testing can be used to detect a mutation in FGFR3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301331", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 668, "text": "Achondroplasia comes from the genetic point mutations in the fibroblastic growth factor receptor 3 gene (FGFR3), which enables abnormal cartilage growth-plate differentiation and insufficient bony development. The most common genetic mutations in this receptor are G to A at position 1138 (G1138A), which result in the substitution of glycine to arginine at codon 380.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15221641", "endSection": "abstract" }, { "offsetInBeginSection": 23, "offsetInEndSection": 338, "text": "To investigate the mutation at the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying the major pathologic mechanism of achondroplasia (ACH) and to evaluate the efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening the point mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12048679", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1180, "text": "Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12048679", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 1050, "text": "The nucleotide 1138 of FGFR3 gene is also the hotspot of mutation in Chinese patients with ACH. A simple and rapid molecular diagnostic method has been set up to differentiate ACH from other similar genetic dwarfism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10932008", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 580, "text": "The diagnosis of achondroplasia was based on the presence of clinical and radiographic findings and confirmed by the presence of a common FGFR3 gene mutation (Gly380Arg) detected by restriction enzyme analysis and sequencing of the polymerase chain reaction products.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10881785", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 407, "text": "All patients carried the same glycine-to-arginine mutation at codon 380(G380R) of the transmembrane domain of FGFR3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9949234", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 728, "text": "The results suggest that the G380R mutation of FGFR3 is also a frequent mutation causing achondroplasia in Chinese. Detecting FGFR 3 gene mutation with PCR-SSCP and restriction enzymes analysis is a convenient, rapid and reliable molecular diagnostic assay for prenatal and early diagnosis of achondroplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9949234", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 160, "text": "To evaluate whether mutation in the exon 10 of the fibroblast growth factor receptor 3(FGFR3) gene in common in Chinese patients with achondroplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9949234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "Achondroplasia (ACH) is the most frequent form of short-limb dwarfism. Recently, the gene mutation responsible for ACH has been identified in the transmembrane domain of the fibroblast growth factor receptor 3 gene. The cause of ACH is a point mutation at nucleotide 1138 of the cDNA, resulting in the substitution of an arginine residue for a glycine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9115628", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 420, "text": "Recent studies mapped the achondroplasia gene on chromosome region 4p16.3 and identified a common mutation in the gene encoding the fibroblast growth factor receptor 3 (FGFR3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7702086", "endSection": "abstract" } ] }, { "body": "What is the mode of action of Hsp90 inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18852131", "http://www.ncbi.nlm.nih.gov/pubmed/18347135", "http://www.ncbi.nlm.nih.gov/pubmed/15849317", "http://www.ncbi.nlm.nih.gov/pubmed/10962573" ], "ideal_answer": [ "Pharmacologic inhibition of Hsp90 involves interaction with the ATP-binding site of the chaperone. This exerts antiproliferative effects resulting in a marked suppression of tumor growth. Following treatment with a Hsp90 inhibitor, expression of a number of proteins is affected, and most notably the Hsp90 clients, leading to dysregulation of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism, finally resulting in cancer cell death through activation of both intrinsic and extrinsic apoptotic pathways." ], "concepts": [ "http://www.uniprot.org/uniprot/HSP82_ENCCU", "http://www.uniprot.org/uniprot/HSP90_THEPA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051879", "http://www.uniprot.org/uniprot/HSP90_ASPFU", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018841", "http://www.uniprot.org/uniprot/HSP90_BRUPA", "http://www.biosemantics.org/jochem#4250710", "http://www.uniprot.org/uniprot/HSP90_EIMTE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.uniprot.org/uniprot/H90A1_DANRE", "http://www.biosemantics.org/jochem#4175054", "http://www.uniprot.org/uniprot/HSP90_THEAN" ], "type": "summary", "id": "5309fa5e970c65fa6b000003", "snippets": [ { "offsetInBeginSection": 432, "offsetInEndSection": 608, "text": "In vitro, we show that pharmacologic inhibition of Hsp90 by IPI-504 exerts antiproliferative effects in a panel of pancreatic cancer cells in a dose- and time-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18852131", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 754, "text": "In pancreatic cancer xenografts obtained directly from patients with pancreas cancer, the agent resulted in a marked suppression of tumor growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18852131", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1589, "text": "Using a proteomic profiling analysis with isotope tags for relative and absolute quantitation labeling technique, we have identified 20 down-regulated proteins and 42 up-regulated proteins on IPI-504 treatment.tumor growth Identical changes were observed in the expression of the genes coding for these proteins in a subset of proteins including HSPA1B, LGALS3, CALM1, FAM84B, FDPS, GOLPH2, HBA1, HIST1H1C, HLA-B, and MARCKS. The majority of these proteins belong to the functional class of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18852131", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 403, "text": "Dicoumarol, a long-established oral anticoagulant, is a new Hsp90 inhibitor that represses PTTG1/Securin gene expression and provokes apoptosis through a complex trait involving both intrinsic and extrinsic pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347135", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 584, "text": "Dicoumarol activity as an Hsp90 inhibitor is confirmed by smaller levels of Hsp90 clients in treated cells and inhibition of in vivo heat shock luciferase activity recovery assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347135", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 707, "text": "Likewise, established Hsp90 inhibitors (17-allylamino-geldanamycin and novobiocin) repress PTTG1/Securin gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347135", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1185, "text": "However, effects on PTTG1/Securin could be partially ascribed to inhibition of the Ras/Raf/extracellular signal-regulated kinase pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347135", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 620, "text": "To document this field, we have studied two Hsp90 inhibitors (radicicol and geldanamycin), known to interact with the ATP-binding site of Hsp90 (the Bergerat fold),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15849317", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 481, "text": "One of these is the novel agent 17-allylamino-17-demethoxygeldanamycin that acts to inhibit the hsp90 molecular chaperone. Treatment of four human colon cancer cell lines with iso-effective concentrations of this agent resulted in depletion of c-raf-1 and akt and inhibition of signal transduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10962573", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 747, "text": "The expression of hsp90 client protein genes was not affected, but hsc hsp70, hsp90beta, keratin 8, keratin 18 and caveolin-1 were deregulated following treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10962573", "endSection": "abstract" } ] }, { "body": "Is RET the major gene involved in Hirschsprung disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12865274", "http://www.ncbi.nlm.nih.gov/pubmed/22574178", "http://www.ncbi.nlm.nih.gov/pubmed/16816022", "http://www.ncbi.nlm.nih.gov/pubmed/22131258", "http://www.ncbi.nlm.nih.gov/pubmed/23400839", "http://www.ncbi.nlm.nih.gov/pubmed/17108762", "http://www.ncbi.nlm.nih.gov/pubmed/16986122", "http://www.ncbi.nlm.nih.gov/pubmed/23372769", "http://www.ncbi.nlm.nih.gov/pubmed/9727738", "http://www.ncbi.nlm.nih.gov/pubmed/16877807", "http://www.ncbi.nlm.nih.gov/pubmed/16441254", "http://www.ncbi.nlm.nih.gov/pubmed/22584707", "http://www.ncbi.nlm.nih.gov/pubmed/16448984", "http://www.ncbi.nlm.nih.gov/pubmed/10664228", "http://www.ncbi.nlm.nih.gov/pubmed/10790203", "http://www.ncbi.nlm.nih.gov/pubmed/20598273", "http://www.ncbi.nlm.nih.gov/pubmed/22344793", "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "http://www.ncbi.nlm.nih.gov/pubmed/21995290", "http://www.ncbi.nlm.nih.gov/pubmed/18285831", "http://www.ncbi.nlm.nih.gov/pubmed/17965226", "http://www.ncbi.nlm.nih.gov/pubmed/7883791" ], "ideal_answer": [ "The RET proto-oncogene is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology.", "RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology " ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10487", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051096" ], "type": "yesno", "id": "5503121de9bde69634000019", "snippets": [ { "offsetInBeginSection": 284, "offsetInEndSection": 477, "text": "The RET proto-oncogene is the major gene associated to HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23372769", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 465, "text": "The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22574178", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 238, "text": "The rearranged during transfection gene (RET) is considered the major gene in HSCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22131258", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 209, "text": "RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21995290", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 988, "text": "While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17965226", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 545, "text": " The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22584707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16441254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17108762", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 390, "text": " Hirschsprung disease (HSCR), a developmental disorder characterized by the absence of enteric neurons in distal segments of the gut, shows a complex pattern of inheritance, with the RET protooncogene acting as a major gene and additional susceptibility loci playing minor roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16986122", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 334, "text": " Traditional RET germline mutations account for a small subset of Hirschsprung disease patients, but several studies have shown that there is a specific haplotype of RET associated with the sporadic forms of Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17108762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "PURPOSE: The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17108762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The RET proto-oncogene is the major gene involved in the pathogenesis of Hirschsprung (HSCR), a complex genetic disease characterized by lack of ganglia along variable lengths of the gut.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16448984", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 437, "text": "While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400839", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 547, "text": "The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22584707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 413, "text": "The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C-->T allele (rs2435357: p = 3.9 x 10(-43) in European ancestry; p = 1.1 x 10(-21) in Chinese samples) that probably arose once within the intronic RET enhancer MCS+9.7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598273", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 391, "text": "Hirschsprung disease (HSCR), a developmental disorder characterized by the absence of enteric neurons in distal segments of the gut, shows a complex pattern of inheritance, with the RET protooncogene acting as a major gene and additional susceptibility loci playing minor roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16986122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: The RET gene encodes a tyrosine kinase receptor involved in different human neurocristopathies, such as specific neuroendocrine tumours and Hirschsprung disease (HSCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12865274", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 539, "text": "The first major susceptibility gene for Hirschsprung disease is the RET proto-oncogene on 10q11.2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9727738", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 883, "text": "The developmental abnormalities apparent in these mice, together with the observation that the major tissues affected in MEN 2 and Hirschsprung disease have a common origin in the embryonal neural crest, suggest that RET encodes a receptor for a developmental regulator involved in the genesis of a variety of neural crest derivatives, and in the organogenesis of the kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7883791", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 213, "text": "RET is the major gene involved in HSCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790203", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 221, "text": "Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16877807", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 612, "text": "Although with several genes involved in its pathogenesis, the major HSCR gene is the RET proto-oncogene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22344793", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 285, "text": "In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The RET proto-oncogene is the major gene involved in the pathogenesis of Hirschsprung (HSCR), a complex genetic disease characterized by lack of ganglia along variable lengths of the gut", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16448984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16441254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17108762", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 402, "text": "Analysis of the RET gene, the major gene involved in HSCR susceptibility, revealed neither linkage nor mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16816022", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 212, "text": "RET is the major gene involved in HSCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790203", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 611, "text": "Although with several genes involved in its pathogenesis, the major HSCR gene is the RET proto-oncogene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22344793", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 436, "text": "While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400839", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 546, "text": "The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22584707", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 220, "text": "Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16877807", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 284, "text": "In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "We report on mutation analysis of five genes involved in the receptor tyrosine kinase (RET) or the endothelin-signalling pathways in 28 sporadic Japanese patients with Hirschsprung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664228", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1465, "text": "In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664228", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 353, "text": "The RET gene is the major HSCR gene, although reduced penetrance of RET mutations and variable expression of HSCR phenotype indicates that more than one gene is required", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285831", "endSection": "abstract" } ] }, { "body": "Which type of lung cancer is the most strongly associated with Lambert-Eaton syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8568672", "http://www.ncbi.nlm.nih.gov/pubmed/18032743", "http://www.ncbi.nlm.nih.gov/pubmed/16100656", "http://www.ncbi.nlm.nih.gov/pubmed/9094058", "http://www.ncbi.nlm.nih.gov/pubmed/9254841", "http://www.ncbi.nlm.nih.gov/pubmed/19803409", "http://www.ncbi.nlm.nih.gov/pubmed/1339000", "http://www.ncbi.nlm.nih.gov/pubmed/1318636", "http://www.ncbi.nlm.nih.gov/pubmed/2189179", "http://www.ncbi.nlm.nih.gov/pubmed/18644631", "http://www.ncbi.nlm.nih.gov/pubmed/20392978", "http://www.ncbi.nlm.nih.gov/pubmed/8009147", "http://www.ncbi.nlm.nih.gov/pubmed/18841652", "http://www.ncbi.nlm.nih.gov/pubmed/20514935", "http://www.ncbi.nlm.nih.gov/pubmed/2833535", "http://www.ncbi.nlm.nih.gov/pubmed/1448671", "http://www.ncbi.nlm.nih.gov/pubmed/10486838", "http://www.ncbi.nlm.nih.gov/pubmed/7731034", "http://www.ncbi.nlm.nih.gov/pubmed/9538660", "http://www.ncbi.nlm.nih.gov/pubmed/20979723", "http://www.ncbi.nlm.nih.gov/pubmed/18506722", "http://www.ncbi.nlm.nih.gov/pubmed/3016531", "http://www.ncbi.nlm.nih.gov/pubmed/8186692", "http://www.ncbi.nlm.nih.gov/pubmed/15793845", "http://www.ncbi.nlm.nih.gov/pubmed/15767964", "http://www.ncbi.nlm.nih.gov/pubmed/12632823", "http://www.ncbi.nlm.nih.gov/pubmed/9484375", "http://www.ncbi.nlm.nih.gov/pubmed/1470196", "http://www.ncbi.nlm.nih.gov/pubmed/15000529", "http://www.ncbi.nlm.nih.gov/pubmed/8387255", "http://www.ncbi.nlm.nih.gov/pubmed/17395141" ], "ideal_answer": [ "Small-cell lung cancer is most commonly associated with Lambert-Eaton syndrome. Case reports suggest that other non-small-cell lung cancer types, such as large-cell neuroendocrine carcinoma and squamous cell carcinoma, can be also very rarely associated this syndrome." ], "exact_answer": [ "small-cell lung cancer" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015624", "http://www.disease-ontology.org/api/metadata/DOID:3905", "http://www.disease-ontology.org/api/metadata/DOID:1324", "http://www.disease-ontology.org/api/metadata/DOID:0050214", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008175" ], "type": "factoid", "id": "5147c088d24251bc05000026", "snippets": [ { "offsetInBeginSection": 1592, "offsetInEndSection": 1792, "text": "The autoantibodies implicated in the Lambert-Eaton myasthenic syndrome (LES), which are known to inhibit ICa and INa in bovine adrenal chromaffin cells, also significantly inhibited INa in SCLC cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7731034", "endSection": "sections.0" }, { "offsetInBeginSection": 1793, "offsetInEndSection": 2211, "text": "These results indicate that (i) action potentials in human SCLC cells result from the regenerative increase in voltage-gated Na+ channel conductance; (ii) fundamental characteristics of SCLC Na+ channels are the same as the classical sodium channels found in a variety of excitable cells; and (iii) in some LES patients, SCLC Na+ channels are an additional target of the pathological IgG present in the patients' sera.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7731034", "endSection": "sections.0" }, { "offsetInBeginSection": 110, "offsetInEndSection": 369, "text": "Clinical features were those of LES and occurred insidiously in this 68-year old man: proximal weakness predominant in the lower limbs, generalized areflexia, dryness of the mouth and partial right eye palsy. Investigations disclosed a small cell lung cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8009147", "endSection": "sections.0" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1240, "text": "Voltage-gated Ca2+ channels may be important to the secretion of ectopic hormones and the etiology and pathogenesis of Lambert-Eaton syndrome, an autoimmune disorder of the motor nerve terminal in which autoantibodies directed against voltage-gated Ca2+ channels are produced.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1318636", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Lambert-Eaton syndrome is a myasthenia-like syndrome of paraneoplastic origin which is often associated with anaplastic small-cell lung cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1339000", "endSection": "sections.0" }, { "offsetInBeginSection": 185, "offsetInEndSection": 247, "text": "Small-cell lung cancer (SCLC) is the most common cause of LES.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18506722", "endSection": "sections.0" }, { "offsetInBeginSection": 248, "offsetInEndSection": 353, "text": "We report an unusual case of LES associated with large-cell neuroendocrine carcinoma (LCNEC) of the lung.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18506722", "endSection": "sections.0" }, { "offsetInBeginSection": 406, "offsetInEndSection": 553, "text": "The Lambert-Eaton syndrome is caused by antibodies against voltage-gated calcium channels and often occurs in patients with small cell lung cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17395141", "endSection": "sections.0" }, { "offsetInBeginSection": 214, "offsetInEndSection": 560, "text": "A 53 year-old heavy smoker presented with a Lambert-Eaton myasthenic syndrome (LEMS). Bronchoscopy was normal but radiological examinations revealed a lymph node in site 4R. The pathological diagnosis after mediastinoscopy was negative. Twenty-five months later, an opacity on chest X-ray led to a biopsy which revealed a squamous cell carcinoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15767964", "endSection": "sections.0" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1019, "text": "LEMS is generally associated with small cell lung cancer occurring in three percent of cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15767964", "endSection": "sections.0" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1202, "text": "However, the case that we report shows the unusual association of LEMS with non small-cell lung cancer and highlights the difficulties associated in the management of this condition.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15767964", "endSection": "sections.0" }, { "offsetInBeginSection": 1672, "offsetInEndSection": 1824, "text": "LEMS has a high degree of coincidence (approximately 60%) with small cell lung cancer; the remaining 40% of patients with LEMS have no detectable tumor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15000529", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND: To enhance the acknowledgement of Lambert-Eaton syndrome in patients with small cell lung cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20979723", "endSection": "sections.0" }, { "offsetInBeginSection": 455, "offsetInEndSection": 555, "text": "There were 10 cases of Lambert-Eaton syndrome in 332 pathologically diagnosed small cell lung cancer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20979723", "endSection": "sections.0" }, { "offsetInBeginSection": 800, "offsetInEndSection": 886, "text": "Treatment of small cell lung cancer may improve the symptoms of Lambert-Eaton syndrome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20979723", "endSection": "sections.0" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1140, "text": "Improving the recognition of Lambert-Eaton syndrome may be helpful to identify early small cell lung cancer and improve the prognosis,as the symptom of muscular weakness usually appears early before the diagnosis of small cell lung cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20979723", "endSection": "sections.0" }, { "offsetInBeginSection": 799, "offsetInEndSection": 1001, "text": "The Lambert Eaton syndrome is a paraneoplastic manifestation of small-cell lung cancer in 50% of the cases unlike generalized myasthenia which apparently is never associated with small-cell lung cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10486838", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Paraneoplastic Lambert-Eaton myasthenia syndrome is presented in two cases with small cell lung cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9538660", "endSection": "sections.0" }, { "offsetInBeginSection": 3, "offsetInEndSection": 280, "text": "Human small-cell lung cancer (SCLC) cells are believed to express the antigens responsible for the production of pathological antibodies in the Lambert-Eaton syndrome (LES), a Ca2+ channel disorder in which quantal transmitter release from the motor nerve terminal is impaired.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8568672", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic autoimmune disorder caused by an IgG-mediated reduction in number of presynaptic voltage-gated calcium channels (VGCC) at the neuromuscular junction. In at least 50% of cases, the stimulus for antibody production may be VGCC on small cell lung cancer (SCLC)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2833535", "endSection": "sections.0" }, { "offsetInBeginSection": 691, "offsetInEndSection": 804, "text": "Also, there was no obvious band pattern distinguishing patients with LES from those with LES and concurrent SCLC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1470196", "endSection": "sections.0" }, { "offsetInBeginSection": 157, "offsetInEndSection": 279, "text": "The cancer associated with LEMS was small-cell lung carcinoma (SCLC) in 15 cases and epidermoid lung carcinoma in 3 cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1448671", "endSection": "sections.0" }, { "offsetInBeginSection": 501, "offsetInEndSection": 698, "text": "Etiology of this disease is uncertain but in view of its frequent association with small cell lung cancer, this specific type of neoplasm may be implicated in the initiation of autoimmune response.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2189179", "endSection": "sections.0" }, { "offsetInBeginSection": 699, "offsetInEndSection": 881, "text": "Recent studies indeed support the possibility that the antigenic stimulus in the neoplastic form of LES may arise from voltage-dependent Ca2+ channels found in the lung cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2189179", "endSection": "sections.0" }, { "offsetInBeginSection": 2007, "offsetInEndSection": 2220, "text": "In the majority of LEMS patients, those having detectable tumor, the disease is thought to occur as a result of immune response directed initially against voltage-gated Ca2+ channels found on the lung tumor cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15000529", "endSection": "sections.0" }, { "offsetInBeginSection": 620, "offsetInEndSection": 781, "text": "Radiological, bronchoscopic and histological investigations revealed small-cell lung cancer, and neurophysiological investigations confirmed a diagnosis of LEMS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20392978", "endSection": "sections.0" }, { "offsetInBeginSection": 1787, "offsetInEndSection": 1996, "text": "Physicians need to be aware that patients may develop PCD and LEMS associated with anti-VGCC antibody caused by small cell lung cancer, and a mass survey should be conducted and careful examinations performed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19803409", "endSection": "sections.0" }, { "offsetInBeginSection": 329, "offsetInEndSection": 525, "text": "Biopsy revealed small cell lung cancer (SCLC) indicating the importance of repeated chest CT in LEMS even when an existing autoimmune-like disease and negative CT may suggest an autoimmune origin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18841652", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND: Neuromuscular symptoms in patients with Lambert-Eaton myasthenic syndrome (LEMS) and a small cell lung cancer (SCLC) develop more rapidly than in LEMS patients without a SCLC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18644631", "endSection": "sections.0" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1630, "text": "The detection of SOX1 antibodies in patients with Lambert-Eaton myasthenic syndrome (LEMS) predicts the presence of small cell lung cancer and may be used to follow more closely those LEMS patients with no evidence of cancer at the initial workup.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18032743", "endSection": "sections.0" }, { "offsetInBeginSection": 738, "offsetInEndSection": 954, "text": "The presence of a particular symptom associated with LEMS did not predict the presence of SCLC, but in patients with rapidly progressive LEMS the possibility of underlying lung cancer should be of particular concern.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15793845", "endSection": "sections.0" }, { "offsetInBeginSection": 288, "offsetInEndSection": 520, "text": "We report a case of small-cell lung cancer (SCLC) presenting with LEMS and ventilatory failure in a 67-year-old man who initially presented with progressive limb weakness for 6 months and tachypnea with shallow breathing for 1 week.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12632823", "endSection": "sections.0" }, { "offsetInBeginSection": 442, "offsetInEndSection": 638, "text": "Using this protein, we demonstrated that anti-beta-subunit antibodies are present in the sera of 23% of LEMS patients and only, in low titer, in 2% of small cell lung cancer patients without LEMS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9484375", "endSection": "sections.0" }, { "offsetInBeginSection": 291, "offsetInEndSection": 543, "text": "The gene encoding the beta 2 protein, first described as a Lambert-Eaton myasthenic syndrome (LEMS) antigen in humans, is found close to a region that undergoes chromosome rearrangements in small cell lung cancer, which occurs in association with LEMS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9254841", "endSection": "sections.0" }, { "offsetInBeginSection": 449, "offsetInEndSection": 719, "text": "We then tested sera from 72 LEMS patients' 25 with proven small cell lung cancer (SCLC) and 66 healthy or other neurological, SCLC or autoimmune disease controls in an immunoprecipitation assay using 125I-omega-CmTx-labelled (P/Q-type) VGCCs in human cerebellar extract.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9094058", "endSection": "sections.0" }, { "offsetInBeginSection": 471, "offsetInEndSection": 553, "text": "In the majority of patients LEMS is associated with small cell lung cancer (SCLC).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8186692", "endSection": "sections.0" }, { "offsetInBeginSection": 207, "offsetInEndSection": 344, "text": "Patients with small cell lung cancer (SCLC) in particular may develop LEMS, and SCLC is very often detected in patients affected by LEMS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8387255", "endSection": "sections.0" }, { "offsetInBeginSection": 264, "offsetInEndSection": 539, "text": "We present a 69-year-old woman who had preventive whole brain radiation after a diagnosis of paraneoplastic Lambert-Eaton syndrome related to small cell lung cancer Five months after radiation therapy, she developed radiation-induced leukoencephalopathy manifested by ataxia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20514935", "endSection": "sections.0" }, { "offsetInBeginSection": 176, "offsetInEndSection": 248, "text": "Among the symptoms of lung cancer LEMS can be seen, but it is very rare.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16100656", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "A patient with the Lambert-Eaton syndrome (LES) and small cell lung cancer developed respiratory failure several hours after verapamil was given.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3016531", "endSection": "sections.0" } ] }, { "body": "What distinguishes lantibiotics from antibiotics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12361237", "http://www.ncbi.nlm.nih.gov/pubmed/19009315", "http://www.ncbi.nlm.nih.gov/pubmed/1482192", "http://www.ncbi.nlm.nih.gov/pubmed/21905643", "http://www.ncbi.nlm.nih.gov/pubmed/11945173", "http://www.ncbi.nlm.nih.gov/pubmed/24069959", "http://www.ncbi.nlm.nih.gov/pubmed/21470152", "http://www.ncbi.nlm.nih.gov/pubmed/23168402", "http://www.ncbi.nlm.nih.gov/pubmed/8264800", "http://www.ncbi.nlm.nih.gov/pubmed/25787977", "http://www.ncbi.nlm.nih.gov/pubmed/23475977", "http://www.ncbi.nlm.nih.gov/pubmed/15044440", "http://www.ncbi.nlm.nih.gov/pubmed/24621781", "http://www.ncbi.nlm.nih.gov/pubmed/24210177", "http://www.ncbi.nlm.nih.gov/pubmed/19393544" ], "ideal_answer": [ "Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials.", "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. Low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Nisin is the oldest and the most widely used lantibiotic, in food preservation, without having developed any significant resistance against it.", "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides." ], "exact_answer": [ "Lantibiotics are post-translationally modified natural peptides containing lanthionine" ], "concepts": [ "http://www.biosemantics.org/jochem#4275453", "http://www.biosemantics.org/jochem#4260744" ], "type": "factoid", "id": "5719f5c67de986d80d00000d", "snippets": [ { "offsetInBeginSection": 124, "offsetInEndSection": 339, "text": "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25787977", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 460, "text": "low levels of resistance have been reported for lantibiotics compared with commercial antibiotics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25787977", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 877, "text": "Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25787977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Lantibiotics are biologically active peptides produced by Gram-positive bacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23168402", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 269, "text": "Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24069959", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 287, "text": "Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24621781", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 422, "text": "Lantibiotics are ribosomally synthesized peptide antibiotics that are posttranslationally modified to introduce (methyl)lanthionine bridges.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Lantibiotics are defined as peptide antibiotics containing the unusual amino acids mesolanthionine, 3-methyllanthionine, dehydroalanine, and dehydrobutyrine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8264800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Lantibiotics are antibiotic peptides distinguished by the presence of the rare thioether amino acids lanthionine and/or methyllanthionine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11945173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Lantibiotics are ribosomally synthesized, post-translationally modified, peptide antibiotics containing unusual amino acids such as dehydrated amino acids and lanthionine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Lantibiotics are peptide antibiotics, realizing their unique secondary structure by posttranslational modifications, the most important one being the formation of the characteristic amino acid lanthionine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21905643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Lantibiotics are lanthionine-containing peptide antibiotics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15044440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Lantibiotics, a group of lanthionine-containing peptides, display their antibiotic activity by combining different killing mechanisms within one molecule. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009315", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 697, "text": "Lantibiotics are ribosomally synthesized as prepeptides, which are posttranslationally modified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8264800", "endSection": "abstract" } ] }, { "body": "List three major features of the CCFDN syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10439962", "http://www.ncbi.nlm.nih.gov/pubmed/25186864", "http://www.ncbi.nlm.nih.gov/pubmed/17195938", "http://www.ncbi.nlm.nih.gov/pubmed/14512967", "http://www.ncbi.nlm.nih.gov/pubmed/11805249", "http://www.ncbi.nlm.nih.gov/pubmed/19070320", "http://www.ncbi.nlm.nih.gov/pubmed/17578274", "http://www.ncbi.nlm.nih.gov/pubmed/15234148", "http://www.ncbi.nlm.nih.gov/pubmed/14517542", "http://www.ncbi.nlm.nih.gov/pubmed/16939648", "http://www.ncbi.nlm.nih.gov/pubmed/10442556", "http://www.ncbi.nlm.nih.gov/pubmed/10360766" ], "ideal_answer": [ "Congenital cataracts, facial dysmorphism and peripheral neuropathy are three major features of the CCFDN syndrome. Other described signs and symptoms of the CCFDN syndrome include microcornea, microphthalmos, micropupil, floppy eyelid syndrome, pseudoptosis, nystagmus, congenital esotropia, impairment of distant visual acuity, ataxia, pyramidal signs, mild chorea, short stature, muscular atrophy, delayed early motor and intellectual development, hypogonadotrop hypogonadism, hypomyelination of the peripheral nervous system, serious complications related to general anaesthesia and parainfectious rhabdomyolysis." ], "exact_answer": [ [ "congenital cataracts" ], [ "facial dysmorphism" ], [ "peripheral neuropathy" ] ], "type": "list", "id": "5503263fe9bde69634000030", "snippets": [ { "offsetInBeginSection": 1028, "offsetInEndSection": 1468, "text": "Because of our experience in neuromuscular disorders, we choose six, frequent, autosomal recessive disorders for these clinical and genetic studies: hereditary motor and sensory neuropathy type Lom (HMSNL), hereditary motor and sensory neuropathy type Russe (HMSNR), congenital cataracts facial dysmorphism syndrome (CCFDN), limb-girdle muscular dystrophy 2C (LGMD2C), congenital myasthenic syndrome (CMS) and spinal muscular atrophy (SMA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome (OMIM 604168) is a recently described autosomal recessive developmental disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part of the clinical management of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17195938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16939648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "OBJECTIVE: To determine the nature and course of ophthalmologic abnormalities in congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome in a genetically verified group of 9 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15234148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome (OMIM 604168) is an autosomal recessive developmental disorder that occurs in an endogamous group of Vlax Roma (Gypsies; refs. 1-3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14517542", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 587, "text": "The major differential diagnosis of MSS is the syndrome defined by congenital cataracts, facial dysmorphism and peripheral neuropathy (CCFDN), which is localised to 18qter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14512967", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 599, "text": "The CCFDN syndrome is a complex phenotype involving multiple systems, characterized by facial dysmorphism, congenital cataracts, microcorneae, delayed early motor and intellectual development, hypogonadotrop hypogonadism, hypomyelination of the peripheral nervous system, and serious complications related to general anaesthesia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578274", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 623, "text": "Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, mild facial dysmorphism and hypogonadism. Para-infectious rhabdomyolysis is a serious complication reported in an increasing number of patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16939648", "endSection": "abstract" }, { "offsetInBeginSection": 1755, "offsetInEndSection": 1972, "text": "CONCLUSIONS: Early-onset congenital cataracts associated with microcornea, microphthalmos, and micropupil are essential ocular features of the CCFDN syndrome and are the first recognizable signs during early infancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15234148", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1427, "text": "All patients showed a peripheral, demyelinating neuropathy and varying degrees of ataxia. In the older patients, muscular atrophy in distal muscles and facial dysmorphism was evident. Early-onset bilateral congenital cataracts associated with microcornea, microphthalmos, and micropupil could be found in all patients. All children had floppy eyelid syndrome and pseudoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15234148", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1754, "text": "All patients had syndrome-associated nystagmus and congenital esotropia. Distant visual acuity could be classified as severe to moderate impairment, whereas near visual acuity was much better (mild to moderate impairment).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15234148", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 577, "text": "Because these families originated from the same genetically isolated founder population as did patients with congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome, and because the two syndromes have clinical manifestations in common, we hypothesized that the two related, albeit distinct, syndromes may represent clinical variants of a single genetic disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11805249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Peripheral nerve abnormalities in the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10442556", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10439962", "endSection": "title" }, { "offsetInBeginSection": 196, "offsetInEndSection": 295, "text": "We propose to refer to the syndrome as congenital cataracts facial dysmorphism neuropathy (CCFDN). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10439962", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 357, "text": "The disorder has been termed the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome to emphasize its salient features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10360766", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1302, "text": "Associated neurological features are a moderate nonprogressive cognitive deficit in most affected individuals together with pyramidal signs and mild chorea in some. Accompanying nonneurological features include short stature, characteristic facial dysmorphism, and hypogonadotrophic hypogonadism. Nerve conduction studies suggest a hypomyelinating/demyelinating neuropathy, confirmed by nerve biopsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10360766", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17195938", "endSection": "title" }, { "offsetInBeginSection": 1755, "offsetInEndSection": 1971, "text": "CONCLUSIONS: Early-onset congenital cataracts associated with microcornea, microphthalmos, and micropupil are essential ocular features of the CCFDN syndrome and are the first recognizable signs during early infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15234148", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 356, "text": "The disorder has been termed the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome to emphasize its salient features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10360766", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 576, "text": "Because these families originated from the same genetically isolated founder population as did patients with congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome, and because the two syndromes have clinical manifestations in common, we hypothesized that the two related, albeit distinct, syndromes may represent clinical variants of a single genetic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11805249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part of the clinical management of the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17195938", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 586, "text": "The major differential diagnosis of MSS is the syndrome defined by congenital cataracts, facial dysmorphism and peripheral neuropathy (CCFDN), which is localised to 18qter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14512967", "endSection": "abstract" } ] }, { "body": "is intense physical activity associated with longevity ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21925040", "http://www.ncbi.nlm.nih.gov/pubmed/14662259", "http://www.ncbi.nlm.nih.gov/pubmed/12832429", "http://www.ncbi.nlm.nih.gov/pubmed/16355084", "http://www.ncbi.nlm.nih.gov/pubmed/17436206", "http://www.ncbi.nlm.nih.gov/pubmed/23300766", "http://www.ncbi.nlm.nih.gov/pubmed/23241272", "http://www.ncbi.nlm.nih.gov/pubmed/21477204", "http://www.ncbi.nlm.nih.gov/pubmed/12919770", "http://www.ncbi.nlm.nih.gov/pubmed/17036189", "http://www.ncbi.nlm.nih.gov/pubmed/21435018", "http://www.ncbi.nlm.nih.gov/pubmed/22413946", "http://www.ncbi.nlm.nih.gov/pubmed/23450998", "http://www.ncbi.nlm.nih.gov/pubmed/19575156", "http://www.ncbi.nlm.nih.gov/pubmed/21618162", "http://www.ncbi.nlm.nih.gov/pubmed/2279154", "http://www.ncbi.nlm.nih.gov/pubmed/23241269", "http://www.ncbi.nlm.nih.gov/pubmed/22332442" ], "ideal_answer": [ "Several survival studies showed that professional athletes has higher longevity than general population. These epidemiological data matches the evidences that long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality, and also telomere length." ], "exact_answer": "yes", "type": "yesno", "id": "5167be1a298dcd4e5100005c", "snippets": [ { "offsetInBeginSection": 1114, "offsetInEndSection": 1451, "text": "We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21618162", "endSection": "sections.0" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1458, "text": "Competitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450998", "endSection": "sections.0" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1595, "text": "Medallists lived an average of 2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13, 1.09 to 1.17; 1.11, 1.09 to 1.13) than that of medallists in power sports (1.05, 1.01 to 1.08). CONCLUSIONS: Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23241272", "endSection": "sections.0" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1616, "text": "Long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16355084", "endSection": "sections.0" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1822, "text": "Sports activity in adolescents and young adults was associated with an increased risk of SD, both in males and females. Sports, per se, was not a cause of the enhanced mortality, but it triggered SD in those athletes who were affected by cardiovascular conditions predisposing to life-threatening ventricular arrhythmias during physical exercise.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14662259", "endSection": "sections.0" } ] }, { "body": "Are cyclophilins proteins that bind to prolines?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24831536", "http://www.ncbi.nlm.nih.gov/pubmed/12358793", "http://www.ncbi.nlm.nih.gov/pubmed/18823995", "http://www.ncbi.nlm.nih.gov/pubmed/25967372" ], "ideal_answer": [ "Cyclophilins are ubiquitously expressed proteins that bind to prolines." ], "exact_answer": "yes", "type": "yesno", "id": "56f6a63d09dd18d46b00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25967372", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 722, "text": "a characteristic of the cyclophilin family of proteins that bind prolines and often act as cis-trans peptidyl-prolyl isomerases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18823995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The cyclophilins are widely expressed enzymes that catalyze the interconversion of the cis and trans peptide bonds of prolines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24831536", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1564, "text": " an immunophilin on the isomerization of critical prolines that are found in the tCHT1 sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12358793", "endSection": "abstract" } ] }, { "body": "Can a given genotype exhibit opposite fitness effects (beneficial and detrimental) within the same environment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23169561", "http://www.ncbi.nlm.nih.gov/pubmed/15454545", "http://www.ncbi.nlm.nih.gov/pubmed/19226414" ], "ideal_answer": [ "A given genotype can be either beneficial or detrimental, even deleterious, depending on the environment in which an organism lives. This is known as antagonistic pleiotropy. Antagonistic pleiotropy can operate even within the same environment. For example, in Escherichia coli, certain mutations can exhibit beneficial, deleterious or neutral fitness effects at different growth rates. Also, antagonistic pleiotropy is involved in the evolution of ageing, since a certain genotype may affect late- and early-life fitness in opposite directions." ], "exact_answer": "yes", "type": "yesno", "id": "5549f7a1f35db7552600000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Mutations beneficial in one environment may cause costs in different environments, resulting in antagonistic pleiotropy. Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23169561", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 951, "text": "The hfq mutations were beneficial, deleterious or neutral at an intermediate growth rate (0.5\u2009h(-1)) and one changed from beneficial to deleterious within a 36\u2009min difference in doubling time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23169561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Two genetic models exist to explain the evolution of ageing - mutation accumulation (MA) and antagonistic pleiotropy (AP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19226414", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 345, "text": "Under AP, late-acting deleterious mutations accumulate because they confer beneficial effects early in life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19226414", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1135, "text": "Many marker loci responded in opposite directions to selection for late- and early-life fitness, indicating negative genetic correlations or trade-offs between those traits. Indirect evidence suggested that some negative genetic correlations were due to antagonistic pleiotropy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15454545", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 311, "text": "Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23169561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "The basis of antagonistic pleiotropy in hfq mutations that have opposite effects on fitness at slow and fast growth rates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23169561", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 310, "text": "Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23169561", "endSection": "abstract" } ] }, { "body": "Has the protein SETMAR (Metnase) a transposase domain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18263876", "http://www.ncbi.nlm.nih.gov/pubmed/22231448", "http://www.ncbi.nlm.nih.gov/pubmed/20620605", "http://www.ncbi.nlm.nih.gov/pubmed/20309721", "http://www.ncbi.nlm.nih.gov/pubmed/17877369", "http://www.ncbi.nlm.nih.gov/pubmed/16332963", "http://www.ncbi.nlm.nih.gov/pubmed/17130240", "http://www.ncbi.nlm.nih.gov/pubmed/21491884", "http://www.ncbi.nlm.nih.gov/pubmed/18790802", "http://www.ncbi.nlm.nih.gov/pubmed/23090115", "http://www.ncbi.nlm.nih.gov/pubmed/18773976", "http://www.ncbi.nlm.nih.gov/pubmed/20416268", "http://www.ncbi.nlm.nih.gov/pubmed/20521842", "http://www.ncbi.nlm.nih.gov/pubmed/17403897", "http://www.ncbi.nlm.nih.gov/pubmed/16672366", "http://www.ncbi.nlm.nih.gov/pubmed/19458360" ], "ideal_answer": [ "Yes, the protein SETMAR (Metnase) has a transposase domain." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004803", "http://www.uniprot.org/uniprot/SETMR_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019895", "http://www.uniprot.org/uniprot/SETMR_RAT", "http://www.uniprot.org/uniprot/TRAT_CHEHE", "http://www.uniprot.org/uniprot/TRA_BPMU", "http://www.uniprot.org/uniprot/SETMR_MOUSE", "http://www.uniprot.org/uniprot/SETMR_BOVIN" ], "type": "yesno", "id": "54f5f8925f206a0c06000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Metnase (SETMAR) is a SET-transposase fusion protein that promotes nonhomologous end joining (NHEJ) repair in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21491884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20620605", "endSection": "title" }, { "offsetInBeginSection": 93, "offsetInEndSection": 219, "text": " Metnase (also termed SETMAR) is a fusion of a histone methylase and transposase protein that arose specifically in primates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20620605", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 219, "text": "the only intact Hsmar1 transposase gene exists within a chimeric SET-transposase fusion protein referred to as Metnase or SETMAR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20521842", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1253, "text": "The Metnase transposase has been remarkably conserved through evolution;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20521842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "Metnase (also known as SETMAR) is a SET and transposase fusion protein in humans and plays a positive role in double-strand break (DSB) repair. While the SET domain possesses histone lysine methyltransferase activity, the transposase domain is responsible for 5'-terminal inverted repeat (TIR)-specific binding, DNA looping, and DNA cleavage activities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20416268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Metnase is a fusion gene comprising a SET histone methyl transferase domain and a transposase domain derived from the Mariner transposase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20309721", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 589, "text": "ulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Metnase is a human SET and transposase domain protein ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18790802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "The human set and transposase domain protein Metnase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18773976", "endSection": "title" }, { "offsetInBeginSection": 207, "offsetInEndSection": 520, "text": " of transposase-related sequences in humans are pseudogenes. We recently isolated and characterized a SET and transposase domain protein termed Metnase that promotes DNA double-strand break (DSB) repair by non-homologous end-joining (NHEJ). Both the SET and transposase domain were required for its NHEJ activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18773976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Metnase, also known as SETMAR, is a SET and transposase fusion protein with an undefined role in mammalian DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18263876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Biochemical characterization of a SET and transposase fusion protein, Metnase: i", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17877369", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Metnase (SETMAR) is a SET and transposase fusion protein that promotes in vivo end joining activity and mediates genomic integration of foreign DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17877369", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 462, "text": " This transposase coding region is part of the SETMAR gene, in which a histone methylatransferase SET domain is fused to an Hsmar1 transposase domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17403897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17130240", "endSection": "title" }, { "offsetInBeginSection": 183, "offsetInEndSection": 334, "text": "ere we investigate the activity of the human SETMAR protein, a highly expressed fusion between a histone H3 methylase and a mariner family transposase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17130240", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 533, "text": "SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16672366", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 419, "text": "We identified a protein, termed Metnase, that has a SET domain and a transposase/nuclease domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16332963", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 211, "text": "Metnase has a nuclease domain that shares homology with the Transposase family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090115", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 430, "text": "Metnase (also called SETMAR) is a SET and transposase domain protein that promotes both DNA double-strand break (DSB) repair and restart of stalled replication forks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22231448", "endSection": "abstract" } ] }, { "body": "Is alternative splicing of apoptotic genes playing a role in the response to DNA or mitochondrial damage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19450518", "http://www.ncbi.nlm.nih.gov/pubmed/18806759", "http://www.ncbi.nlm.nih.gov/pubmed/9010037", "http://www.ncbi.nlm.nih.gov/pubmed/17692132", "http://www.ncbi.nlm.nih.gov/pubmed/19690168", "http://www.ncbi.nlm.nih.gov/pubmed/21483803", "http://www.ncbi.nlm.nih.gov/pubmed/19170108", "http://www.ncbi.nlm.nih.gov/pubmed/18571879", "http://www.ncbi.nlm.nih.gov/pubmed/18211505", "http://www.ncbi.nlm.nih.gov/pubmed/12067235", "http://www.ncbi.nlm.nih.gov/pubmed/10391249", "http://www.ncbi.nlm.nih.gov/pubmed/22266985" ], "ideal_answer": [ "Yes, alternative splicing seem to play a key role in the response to DNA or mitocondrial damage as suggested by the number of apoptotic genes that are alternatively spliced, with often antagonistic roles of the isoforms generated." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004249", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398" ], "type": "yesno", "id": "5175b97a8ed59a060a00002f", "snippets": [ { "offsetInBeginSection": 596, "offsetInEndSection": 761, "text": "Apoptosis promoted by UV in cells lacking p53 is prevented when the change in AS of the apoptotic gene bcl-x is reverted, confirming the relevance of this mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450518", "endSection": "sections.0" }, { "offsetInBeginSection": 465, "offsetInEndSection": 839, "text": "We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18806759", "endSection": "sections.0" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1204, "text": "This analysis revealed that DNA damage resulted in changes in splicing activity that modified the splicing pattern of Fas, a key pro-apoptotic, p53-inducible death receptor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18571879", "endSection": "sections.0" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1519, "text": "Bortezomib induces mitochondrial damage in native cells and also activates the UPR by splicing of Xbp-1 and induction of CHOP, which is significantly reduced by silencing of MUC4.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266985", "endSection": "sections.0" }, { "offsetInBeginSection": 151, "offsetInEndSection": 507, "text": "The tumour-suppressor protein p53 is an important activator of apoptosis. Although p53-deficient cancer cells are less responsive to chemotherapy, their resistance is not complete, which suggests that other apoptotic pathways may exist. A p53-related gene, p73, which encodes several proteins as a result of alternative splicing, can also induce apoptosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10391249", "endSection": "sections.0" }, { "offsetInBeginSection": 784, "offsetInEndSection": 1110, "text": "Induction of apoptosis was significantly reduced in P388/SPR cells, as indicated by minimal DNA fragmentation. Analysis of oncogenes regulating apoptotic cell death revealed a marked decrease of bcl-2 in combination with a moderate reduction of bax protein, but a striking overexpression of the long form of the bcl-X protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9010037", "endSection": "sections.0" } ] }, { "body": "Which oncogenes are able to induce cellular senescence?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23216904", "http://www.ncbi.nlm.nih.gov/pubmed/19053174", "http://www.ncbi.nlm.nih.gov/pubmed/20010815", "http://www.ncbi.nlm.nih.gov/pubmed/17409421", "http://www.ncbi.nlm.nih.gov/pubmed/17634581", "http://www.ncbi.nlm.nih.gov/pubmed/11971980", "http://www.ncbi.nlm.nih.gov/pubmed/22791394", "http://www.ncbi.nlm.nih.gov/pubmed/22019769", "http://www.ncbi.nlm.nih.gov/pubmed/17664422", "http://www.ncbi.nlm.nih.gov/pubmed/20227040", "http://www.ncbi.nlm.nih.gov/pubmed/16818632", "http://www.ncbi.nlm.nih.gov/pubmed/20237562", "http://www.ncbi.nlm.nih.gov/pubmed/12581156", "http://www.ncbi.nlm.nih.gov/pubmed/21969595", "http://www.ncbi.nlm.nih.gov/pubmed/12134086", "http://www.ncbi.nlm.nih.gov/pubmed/19150958" ], "ideal_answer": [ "Cellular senescence can be induced through activation or inactivation of a number of oncogenes, such as Ras, c-Abl, Raf, Myc, Skp2, BRAF, AKT, HDAC2, p38 MAPK, Caveolin-1 and Mek1." ], "exact_answer": [ [ "Ras" ], [ "c-Abl" ], [ "Raf" ], [ "Myc" ], [ "Skp2" ], [ "BRAF" ], [ "AKT" ], [ "HDAC2" ], [ "p38 MAPK" ], [ "Caveolin-1" ], [ "Mek1" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016922", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000773", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000772", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000774", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016283", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090398", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011905", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018631", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016315", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016313", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016374", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090402" ], "type": "list", "id": "5309f8f5970c65fa6b000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "ROS-generating oxidases Nox1 and Nox4 contribute to oncogenic Ras-induced premature senescence", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23216904", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Activated oncogenes induce premature cellular senescence, a permanent state of proliferative arrest in primary rodent and human fibroblasts. Recent studies suggest that generation of reactive oxygen species (ROS) is involved in oncogenic Ras-induced premature senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23216904", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1397, "text": "these findings suggest that Nox1- and Nox4-generated ROS play an important role in Ras-induced premature senescence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23216904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "A role for c-Abl in cell senescence and spontaneous immortalization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791394", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 497, "text": "Here, we report an important role for c-Abl in replicative senescence and immortalization by regulating the expression of two tumor suppressors that induce cellular senescence, p53 and p16(INK4a).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791394", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1419, "text": "The role for c-Abl in regulating cell senescence and immortalization might explain some of the developmental defects in c-Abl (-/-) mice and how BCR-ABL transforms cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Ras/Raf-prototypic oncogenes induce cellular senescence, a terminal cell-cycle arrest, as a default cellular safeguard program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22019769", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 64, "text": "oncogene-induced senescence, Myc style", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22019769", "endSection": "title" }, { "offsetInBeginSection": 218, "offsetInEndSection": 666, "text": "We review and discuss here evidence for Myc-induced senescence - which is detectable to a limited degree as a cell-autonomous, direct response to Myc action, but occurs predominantly in a non-cell-autonomous fashion via crosstalk of the oncogene-driven cell population with non-neoplastic bystanders, namely cells of the host immune system, prompting them to release pro-senescent cytokines that strike back onto adjacent proliferating tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22019769", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1137, "text": "genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19(Arf)-p53 response is impaired, whereas a Skp2-SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20237562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20227040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Cdk2 suppresses cellular senescence induced by the c-myc oncogene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010815", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 644, "text": "Loss of Cdk2 also caused sensitization to Myc-induced senescence in pancreatic beta-cells or splenic B-cells in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010815", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 887, "text": "Myc also causes senescence in cells lacking the DNA repair protein Wrn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010815", "endSection": "abstract" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1225, "text": "In MEFs, Myc-induced senescence was genetically dependent on the ARF-p53-p21Cip1 and p16INK4a-pRb pathways, p21Cip1 and p16INK4a being selectively induced in Cdk2-/- cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010815", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 362, "text": "We have found that expression of such an oncogene, Akt, causes senescence in primary mouse hepatoblasts in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19150958", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 653, "text": "hyperproliferative signaling through AKT might be a driving force of the senescence in activated hepatic stellate cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19150958", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1238, "text": "oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19053174", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 300, "text": "Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664422", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 372, "text": "MYC inactivation was associated with prototypical markers of senescence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664422", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 938, "text": "only after lymphomas were repaired for p53 expression did MYC inactivation induce robust senescence and sustained tumor regression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664422", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1309, "text": "Replicative senescence due to telomere shortening can, for example, be induced by a dominant negative version of telomerase, premature senescence by the overexpression of oncogenic ras, or p16.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17634581", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 908, "text": "knockdown of HDAC2 induced cellular senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17409421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "MYC overexpression is thought to initiate tumorigenesis by inducing cellular proliferation and growth and to be restrained from causing tumorigenesis by inducing cell cycle arrest, cellular senescence, and/or apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16818632", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 340, "text": "Several conditions, including oncogenic Ras over-expression and inappropriate culture conditions, also induce senescence without telomere shortening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581156", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 700, "text": "We demonstrate that p38 mitogen-activated protein kinase (MAPK) plays important causative roles in senescent cells following telomere shortening, Ras-Raf activation, oxidative stress or inappropriate culture conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581156", "endSection": "title" }, { "offsetInBeginSection": 1359, "offsetInEndSection": 1465, "text": "These results indicate that p38 comprises the senescence-executing pathway in response to diverse stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581156", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1346, "text": "this p38-activating condition appears to be defined quantitatively as a sum of continuous and low-level stresses, and remains even after the initial stimuli are withdrawn, which may explain the well-known irreversible nature of cellular senescence. We also show that papilloma virus E7 abolishes the p38-induced growth arrest but not other senescence-associated phenotypes, indicating the differential role of pRb in the downstream of p38.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Expression of caveolin-1 induces premature cellular senescence in primary cultures of murine fibroblasts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12134086", "endSection": "title" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1224, "text": "Here, we demonstrate that mouse embryonic fibroblasts transgenically overexpressing caveolin-1 show: 1) a reduced proliferative lifespan; 2) senescence-like cell morphology; and 3) a senescence-associated increase in beta-galactosidase activity. These results indicate for the first time that the expression of caveolin-1 in vivo is sufficient to promote and maintain the senescent phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12134086", "endSection": "abstract" }, { "offsetInBeginSection": 1799, "offsetInEndSection": 2028, "text": "Interestingly, premature senescence induced by hydrogen peroxide is greatly reduced in NIH 3T3 cells harboring antisense caveolin-1. Importantly, induction of premature senescence is recovered when caveolin-1 levels are restored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12134086", "endSection": "abstract" }, { "offsetInBeginSection": 2045, "offsetInEndSection": 2138, "text": "these results clearly indicate a central role for caveolin-1 in promoting cellular senescence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12134086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Oncogenic activation of the mitogen-activated protein (MAP) kinase cascade in murine fibroblasts initiates a senescence-like cell cycle arrest that depends on the ARF/p53 tumor suppressor pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11971980", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 841, "text": "In contrast, coexpression of oncogenic ras or activated mek1 with p53 enhanced both p53 levels and activity relative to that observed for p53 alone and produced an irreversible cell cycle arrest that displayed features of cellular senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11971980", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1585, "text": "our results indicate that oncogenic activation of the MAP kinase pathway in murine fibroblasts converts p53 into a senescence inducer through both quantitative and qualitative mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11971980", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 1077, "text": "Myc-evoked apoptosis serves as a signal for macrophage attraction and activation, followed by the secretion of TGF-\u03b2 as a cytokine that is capable of terminally arresting Myc-driven lymphoma cells without causing further DNA damage and without launching a senescence-associated, pro-inflammatory, and, therefore, potentially detrimental cytokine response in the target population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22019769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and/or apoptosis, a phenomenon known as oncogene addiction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21969595", "endSection": "abstract" } ] }, { "body": "What is HbVar?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17221864", "http://www.ncbi.nlm.nih.gov/pubmed/14681476", "http://www.ncbi.nlm.nih.gov/pubmed/21932936", "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "http://www.ncbi.nlm.nih.gov/pubmed/24137000" ], "ideal_answer": [ "HbVar (http://globin.cse.psu.edu) is a relational database of hemoglobin variants and thalassemia mutations. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying \"all beta-globin variants associated with instability and found in Scottish populations.\" This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017085", "http://www.disease-ontology.org/api/metadata/DOID:10241", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017086", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991", "http://www.biosemantics.org/jochem#4249395", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005319", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055538", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006441", "http://www.disease-ontology.org/api/metadata/DOID:1099", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013789" ], "type": "summary", "id": "56c23652ef6e39474100005a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1281, "text": "We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying \"all beta-globin variants associated with instability and found in Scottish populations.\" This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 611, "text": "A registry of these Hb variants and other information, a legacy from Professor Huisman, is now available online, at HbVar database (hhtp://globin.bx.psu.edu/hbvar).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "HbVar (http://globin.bx.psu.edu/hbvar) is a locus-specific database (LSDB) developed in 2001 by a multi-center academic effort to provide timely information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17221864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "HbVar database of human hemoglobin variants and thalassemia mutations: 2007 update.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17221864", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Updates of the HbVar database of human hemoglobin variants and thalassemia mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137000", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681476", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "HbVar (http://globin.bx.psu.edu/hbvar) is a locus-specific database (LSDB) developed in 2001 by a multi-center academic effort to provide timely information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17221864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137000", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 456, "text": "A registry of these Hb variants and other information, a legacy from Professor Huisman, is now available online, at HbVar database (hhtp://globin.bx.psu.edu/hbvar).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932936", "endSection": "abstract" } ] }, { "body": "Can DMSO as an additive improve proteomic analysis results?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18393531", "http://www.ncbi.nlm.nih.gov/pubmed/18926777", "http://www.ncbi.nlm.nih.gov/pubmed/23975139" ], "ideal_answer": [ "Quantitative precisions improved significantly when DMSO (dimethylsulfoxide) was added to the matrix solution.\nIntroducing to the 80% formic acid injection solution an organic solvent such as acetonitrile or acetonitrile-DMSO induced further retention selectivity, and increasing levels of organic solvents reduced on-column retention.\nLow percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold.", "Llow percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold. Additionally, the presence of DMSO in the sample allow the retention time selectivity of the peptides." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004121", "http://www.biosemantics.org/jochem#4275915" ], "type": "summary", "id": "52f89fba2059c6d71c00004f", "snippets": [ { "offsetInBeginSection": 597, "offsetInEndSection": 821, "text": "Introducing to the 80% formic acid injection solution an organic solvent such as acetonitrile or acetonitrile-DMSO induced further retention selectivity, and increasing levels of organic solvents reduced on-column retention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18926777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "We report that low percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23975139", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 464, "text": "We found that the quantitative precisions improved significantly when DMSO (dimethylsulfoxide) was added to the matrix solution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18393531", "endSection": "abstract" } ] }, { "body": "The antibodies MK-3475 and CT-011 have shown promising results in treating malignancies. Which protein are they targeting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23460532", "http://www.ncbi.nlm.nih.gov/pubmed/20460501", "http://www.ncbi.nlm.nih.gov/pubmed/21577144", "http://www.ncbi.nlm.nih.gov/pubmed/23263823", "http://www.ncbi.nlm.nih.gov/pubmed/21710477", "http://www.ncbi.nlm.nih.gov/pubmed/18483370" ], "ideal_answer": [ "Modulation of the immune system by targeting coinhibitory and costimulatory receptors has become a promising new approach of immunotherapy for cancer. OBJECTIVE: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies. We have developed a cancer vaccine in which autologous tumor is fused with dendritic cells resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. The median t1/2 of CT-011 ranged from 217 to 410 hours. The PD1/PDL1 pathway is an important element contributing to tumor-mediated immune suppression. The recent approval of the CTLA-4-blocking antibody ipilimumab for the treatment of melanoma was a watershed event, opening up a new era in the field of immunotherapy. T-cell expression of programmed death receptor-1 down-regulates the immune response against malignancy by interacting with cognate ligands ( eg, PD-L1 ) on tumor cells; however, little is known regarding PD-1 and natural killer ( NK ) cells. ", "PD-1" ], "exact_answer": [ "PD-1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000918", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.disease-ontology.org/api/metadata/DOID:4159", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058950" ], "type": "factoid", "id": "517901bc8ed59a060a00003b", "snippets": [ { "offsetInBeginSection": 293, "offsetInEndSection": 342, "text": "we find that using an anti-PD-1 antibody (CT-011)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21710477", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "PD-1 blockade by CT-011, anti-PD-1 antibody,", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21577144", "endSection": "title" }, { "offsetInBeginSection": 862, "offsetInEndSection": 905, "text": ". Presence of CT-011, an anti-PD1 antibody,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21577144", "endSection": "sections.0" }, { "offsetInBeginSection": 111, "offsetInEndSection": 156, "text": "CT-011, a novel monoclonal anti-PD-1 antibody", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20460501", "endSection": "title" }, { "offsetInBeginSection": 44, "offsetInEndSection": 95, "text": "CT-011, a humanized antibody interacting with PD-1,", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483370", "endSection": "title" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1053, "text": "Anti-PD1 (nivolumab and MK-3475)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460532", "endSection": "sections.0" }, { "offsetInBeginSection": 481, "offsetInEndSection": 509, "text": "anti-PD-1 antibodies MK-3475", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23263823", "endSection": "sections.0" } ] }, { "body": "Which are the different proteins/isoforms encoded but the ASPH (aspartate beta-hydroxylase) gene in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17706594", "http://www.ncbi.nlm.nih.gov/pubmed/17341613", "http://www.ncbi.nlm.nih.gov/pubmed/11007777", "http://www.ncbi.nlm.nih.gov/pubmed/10974562", "http://www.ncbi.nlm.nih.gov/pubmed/17156427", "http://www.ncbi.nlm.nih.gov/pubmed/10956665", "http://www.ncbi.nlm.nih.gov/pubmed/11735129", "http://www.ncbi.nlm.nih.gov/pubmed/15798210" ], "ideal_answer": [ "Alternative splicing of the locus AbetaH-J-J (asparetyl-beta-hydroxylase) generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate). Aspartyl (asparaginyl)-beta-hydroxylase (AAH), has also two related transcripts, Humbug and Junctin, which lack catalytic domains. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila. A human junctin isoform (isoform 1, 225 aa) was also identified and characterized. The isoform 1 has a 15 aa insertion at the amino acid residue 55 of the human junctin." ], "exact_answer": [ [ "Aspartyl-beta-hydroxylase", "Aspartyl (asparaginyl)-beta-hydroxylase", "AbetaH", "AAH", "BAH" ], [ "humbug" ], [ "junctate" ], [ "junctin" ], [ "junctin isoform" ] ], "concepts": [ "http://www.uniprot.org/uniprot/ASPH_BOVIN" ], "type": "list", "id": "5517f9286487737b43000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The single genomic locus, AbetaH-J-J, encodes three functionally distinct proteins aspartyl beta-hydroxylase, junctin and junctate by alternative splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17706594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The human AbetaH-J-J locus is a genomic sequence which generates three functionally distinct proteins, the enzyme aspartyl-beta-hydroxylase (AbetaH), the structural protein of sarcoplasmic reticulum junctin, and the membrane-bound calcium binding protein junctate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341613", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 367, "text": "Aspartyl (asparaginyl)-beta-hydroxylase (AAH) hydroxylates Asp and Asn residues within EGF-like domains of Notch and Jagged, which mediate cell motility and differentiation. This study examines the expression, regulation and function of AAH, and its related transcripts, Humbug and Junctin, which lack catalytic domains, using SH-Sy5y neuroblastoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Alternative splicing of the locus AbetaH-J-J generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15798210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Junctate is a newly identified integral ER/SR membrane calcium binding protein, which is an alternative splicing form of the same gene generating aspartyl beta-hydroxylase and junctin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11735129", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 374, "text": "Screening a mouse heart cDNA library using canine junctin cDNA as a probe yielded three complete mouse heart cDNAs. One of the cDNAs is homologous to the previously reported human junctate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11735129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 641, "text": "Screening a cDNA library from human skeletal muscle and cardiac muscle with a cDNA probe derived from junctin led to the isolation of two groups of cDNA clones. The first group displayed a deduced amino acid sequence that is 84% identical to that of dog heart junctin, whereas the second group had a single open reading frame that encoded a polypeptide with a predicted mass of 33 kDa, whose first 78 NH(2)-terminal residues are identical to junctin whereas its COOH terminus domain is identical to aspartyl beta-hydroxylase, a member of the alpha-ketoglutarate-dependent dioxygenase family. We named the latter amino acid sequence junctate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007777", "endSection": "abstract" }, { "offsetInBeginSection": 1832, "offsetInEndSection": 2080, "text": "Our study shows that alternative splicing of the same gene generates the following functionally distinct proteins: an enzyme (aspartyl beta-hydroxylase), a structural protein of SR (junctin), and a membrane-bound calcium binding protein (junctate).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 864, "text": "Junctin is a calsequestrin binding protein detected in junctional sarcoplasmic reticulum of striated muscles. In the present study, the human cardiac junctin cDNA has been cloned by human heart cDNA library screening and RT-PCR, and the cDNA sequence has been determined. The deduced amino acid sequence of human junctin (210 aa) has 84% sequence identity to that of canine junctin identified previously. A human junctin isoform (isoform 1, 225 aa) was also identified and characterized. The isoform 1 has a 15 aa insertion at the amino acid residue 55 of the human junctin. Northern blot analysis revealed that the human junctin was present both in cardiac and skeletal muscles, and the sizes of the transcripts were approximately 3.0 and 4.2kb. Amino acid residues 6-78 of human junctin and 35-107 of human aspartyl beta-hydroxylase (hAspH) overlapped perfectly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10974562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 610, "text": "The mouse aspartyl beta-hydroxylase gene (Asph, BAH) has been cloned and characterized. The mouse BAH gene spans 200 kilobase pairs of genomic DNA and contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629 and 4,419 base pairs) encode full-length protein and differ only in the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10956665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The single genomic locus, AbetaH-J-J, encodes three functionally distinct proteins aspartyl beta-hydroxylase, junctin and junctate by alternative splicing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17706594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Multiple levels of control of the expression of the human A beta H-J-J locus encoding aspartyl-beta-hydroxylase, junctin, and junctate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341613", "endSection": "title" }, { "offsetInBeginSection": 405, "offsetInEndSection": 486, "text": "A human junctin isoform (isoform 1, 225 aa) was also identified and characterized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10974562", "endSection": "abstract" } ] }, { "body": "List processes which are under the control of the YAP protein.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26109050", "http://www.ncbi.nlm.nih.gov/pubmed/25719868", "http://www.ncbi.nlm.nih.gov/pubmed/25109332", "http://www.ncbi.nlm.nih.gov/pubmed/26125451", "http://www.ncbi.nlm.nih.gov/pubmed/26109051", "http://www.ncbi.nlm.nih.gov/pubmed/26366214", "http://www.ncbi.nlm.nih.gov/pubmed/26039999", "http://www.ncbi.nlm.nih.gov/pubmed/26199863" ], "ideal_answer": [ "Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control, cell poliferation and cancer development and tissue homeostasis and differentiation." ], "exact_answer": [ [ "cell proliferation" ], [ "organ size control" ], [ "cancer development" ], [ "tissue homeostasis" ], [ "cell differentiation" ] ], "type": "list", "id": "56d1d94667f0cb3d66000005", "snippets": [ { "offsetInBeginSection": 732, "offsetInEndSection": 784, "text": "in which YAP appears to regulate cell proliferation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25109332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "YAP and TAZ oncoproteins confer malignancy and drug resistance to various cancer types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26199863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control and cancer development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26039999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are major downstream effectors of the Hippo pathway that influences tissue homeostasis, organ size, and cancer development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26109050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The Hippo signaling pathway converges on YAP to regulate growth, differentiation, and regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26109051", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 511, "text": "Yes associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are its targets and terminal effectors: inhibition of the pathway promotes YAP/TAZ translocation to the nucleus, where they interact with transcriptional enhancer associate domain (TEAD) transcription factors and coactivate the expression of target genes, promoting cell proliferation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25719868", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 325, "text": "Intracellular molecules Yap, Akt, mTOR, and Erk are signaling pathway members that regulate the proliferation of tumor cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26366214", "endSection": "abstract" } ] }, { "body": "What family do mDia proteins belong in?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18230650", "http://www.ncbi.nlm.nih.gov/pubmed/24333164", "http://www.ncbi.nlm.nih.gov/pubmed/24025634", "http://www.ncbi.nlm.nih.gov/pubmed/16487696", "http://www.ncbi.nlm.nih.gov/pubmed/23721065", "http://www.ncbi.nlm.nih.gov/pubmed/24563699", "http://www.ncbi.nlm.nih.gov/pubmed/19160018", "http://www.ncbi.nlm.nih.gov/pubmed/11509578", "http://www.ncbi.nlm.nih.gov/pubmed/21930699", "http://www.ncbi.nlm.nih.gov/pubmed/24242070", "http://www.ncbi.nlm.nih.gov/pubmed/18362183", "http://www.ncbi.nlm.nih.gov/pubmed/14765113", "http://www.ncbi.nlm.nih.gov/pubmed/16303559", "http://www.ncbi.nlm.nih.gov/pubmed/11591323", "http://www.ncbi.nlm.nih.gov/pubmed/16361707", "http://www.ncbi.nlm.nih.gov/pubmed/14519394", "http://www.ncbi.nlm.nih.gov/pubmed/8144827", "http://www.ncbi.nlm.nih.gov/pubmed/17682067", "http://www.ncbi.nlm.nih.gov/pubmed/18239683", "http://www.ncbi.nlm.nih.gov/pubmed/16361249", "http://www.ncbi.nlm.nih.gov/pubmed/22179776", "http://www.ncbi.nlm.nih.gov/pubmed/23060957", "http://www.ncbi.nlm.nih.gov/pubmed/12673949", "http://www.ncbi.nlm.nih.gov/pubmed/23740402", "http://www.ncbi.nlm.nih.gov/pubmed/20869367", "http://www.ncbi.nlm.nih.gov/pubmed/19768111", "http://www.ncbi.nlm.nih.gov/pubmed/10436006", "http://www.ncbi.nlm.nih.gov/pubmed/15371418", "http://www.ncbi.nlm.nih.gov/pubmed/18287523", "http://www.ncbi.nlm.nih.gov/pubmed/12857739", "http://www.ncbi.nlm.nih.gov/pubmed/15096506", "http://www.ncbi.nlm.nih.gov/pubmed/17198702", "http://www.ncbi.nlm.nih.gov/pubmed/21278336", "http://www.ncbi.nlm.nih.gov/pubmed/10629846" ], "ideal_answer": [ "mDia proteins are members of the formin family." ], "exact_answer": [ "mDia proteins are members of the formin family" ], "type": "factoid", "id": "54e0e902ae9738404b000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "mDia proteins are members of the formin family of actin nucleating proteins that polymerize linear actin filaments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23060957", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 703, "text": "mDia1, a linear actin nucleator of the Formin family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24563699", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 373, "text": "the mammalian Diaphanous members of the formin family of proteins (mDia) are two key players in the formation of filopodia and neurites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23740402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "mDia proteins are mammalian homologues of Drosophila diaphanous and belong to the formin family proteins that catalyze actin nucleation and polymerization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18287523", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 232, "text": " The mDia family of formins ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17682067", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 693, "text": "interacts with the formin protein mDia1 (DIAPH1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18230650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Formin-family proteins, in the active state, form actin-based structures such as stress fibres. Their activation mechanisms, however, are largely unknown except that mDia and its closely related formins can be activated by direct binding of the small GTPase Rho or Cdc42.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18239683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Mouse Diaphanous-related formins (mDias) are members of the formin protein family that nucleate actin polymerization and subsequently promote filamentous actin (F-actin) elongation by monomer addition to fast-growing barbed ends.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20869367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Diaphanous related formins (DRFs) are part of the formin protein family that control morphogenesis, embryonic differentiation, cytokinesis, and cell polarity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12857739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Diaphanous related formins (DRFs) are cytoskeleton remodeling proteins that mediate specific upstream GTPase signals to regulate cellular processes such as cytokinesis, cell polarity, and organelle motility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16361249", "endSection": "abstract" } ] }, { "body": "Is nucleosome eviction ATP-dependent?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24068556", "http://www.ncbi.nlm.nih.gov/pubmed/20513433", "http://www.ncbi.nlm.nih.gov/pubmed/17235287", "http://www.ncbi.nlm.nih.gov/pubmed/22177115", "http://www.ncbi.nlm.nih.gov/pubmed/19470761", "http://www.ncbi.nlm.nih.gov/pubmed/19029894", "http://www.ncbi.nlm.nih.gov/pubmed/23460895", "http://www.ncbi.nlm.nih.gov/pubmed/19933844", "http://www.ncbi.nlm.nih.gov/pubmed/24008565" ], "ideal_answer": [ "Yes, nucleosome eviction and chromatin remodelling depends on ATP" ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000786", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006337", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009707", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000255" ], "type": "yesno", "id": "532ff558d6d3ac6a34000037", "snippets": [ { "offsetInBeginSection": 33, "offsetInEndSection": 166, "text": "ATP-dependent chromatin remodeling and nucleosome-depleted 'barriers' co-operate to determine the kinetics of nucleosome organization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068556", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 275, "text": "ATP-dependent nucleosome-remodeling factors endow chromatin with structural flexibility by promoting assembly or disruption of nucleosomes and the exchange of histone variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24008565", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1164, "text": "remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460895", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 735, "text": "which promotes histone deposition onto DNA, and a novel activity, which prevents nucleosome eviction but not remodeling mediated by the ATP-dependent RSC complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177115", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 134, "text": "ATP-dependent chromatin remodeling complex SWI/SNF regulates transcription and has been implicated in promoter nucleosome eviction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20513433", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 122, "text": "ATP-dependent nucleosome-remodeling enzyme involved in transcription, replication, and the DNA damage response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933844", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1430, "text": "Iec1-Ino80 complex promotes transcription through nucleosome eviction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933844", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 323, "text": "Ino80 complex from fission yeast mediates ATP-dependent nucleosome remodeling in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933844", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1153, "text": "reconstitution of nucleosome disassembly using the ATP-dependent chromatin remodeler Rsc and Vps75 revealed that these proteins can cooperate to remove H2A/H2B dimers from nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19470761", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 106, "text": "TP-dependent chromatin-remodeling complexes, such as RSC, can reposition, evict or restructure nucleosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19029894", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 87, "text": "TP-dependent chromatin remodeling complexes play a critical role in chromatin dynamics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235287", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 418, "text": " activity of SWI/SNF to histone eviction in trans from gene promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235287", "endSection": "abstract" } ] }, { "body": "Is TREM2 associated with Alzheimer's disease in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "http://www.ncbi.nlm.nih.gov/pubmed/23462268", "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "http://www.ncbi.nlm.nih.gov/pubmed/17088018", "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "http://www.ncbi.nlm.nih.gov/pubmed/23150934" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_45325250343700D", "o": "http://purl.uniprot.org/core/Gene" } ], "ideal_answer": [ "TREM2 variants have been found to be associated with early as well as with late onset Alzheimer's disease." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/TREM2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "yesno", "id": "51588c34d24251bc05000095", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer's disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23462268", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "sections.0" }, { "offsetInBeginSection": 588, "offsetInEndSection": 637, "text": "possible involvement of TREM2 in AD pathogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "TREM2 is associated with the risk of Alzheimer's disease in Spanish population.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Two recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "endSection": "sections.0" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1044, "text": "we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "endSection": "sections.0" }, { "offsetInBeginSection": 99, "offsetInEndSection": 198, "text": "(TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "endSection": "sections.0" }, { "offsetInBeginSection": 199, "offsetInEndSection": 409, "text": "In this study we examined the association between TREM2 exon 2 variants and early-onset AD in a sample of Caucasian subjects of French origin including 726 patients with age of onset \u226465 years and 783 controls.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "endSection": "sections.0" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1077, "text": "We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150934", "endSection": "sections.0" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1349, "text": "The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150934", "endSection": "sections.0" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1780, "text": "Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E \u03b54 allele.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150934", "endSection": "sections.0" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1806, "text": "CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150934", "endSection": "sections.0" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1128, "text": "RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42\u00d710(-10)).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "endSection": "sections.0" } ] }, { "body": "Which is the most common measure of differences between dinucleotide relative abundance \"genomic signatures\"", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "http://www.ncbi.nlm.nih.gov/pubmed/15046306", "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "http://www.ncbi.nlm.nih.gov/pubmed/9294192", "http://www.ncbi.nlm.nih.gov/pubmed/10430918", "http://www.ncbi.nlm.nih.gov/pubmed/9190805", "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "http://www.ncbi.nlm.nih.gov/pubmed/10066522", "http://www.ncbi.nlm.nih.gov/pubmed/7809131", "http://www.ncbi.nlm.nih.gov/pubmed/18953039" ], "ideal_answer": [ "The concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs). The set of dinucleotide odds ratios or 'general design' is a remarkably stable property of the DNA of an organism, and can be used to discriminate between sequences from different organisms. The average absolute dinucleotide relative abundance difference is termed delta-distance. Delta-distance is the most commonly used measure of differences bwetween \"genomic signatures\". Delta-distances between different genomic sequences in the same species are low, and are generally smaller than the between-species delta-distances." ], "exact_answer": [ "delta-distance" ], "type": "factoid", "id": "554356d0ed966d112c000005", "snippets": [ { "offsetInBeginSection": 594, "offsetInEndSection": 780, "text": "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature',", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953039", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 359, "text": "the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 212, "text": "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 531, "text": "The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 369, "text": "The genome signatures (dinucleotide relative abundance values)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10430918", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 643, "text": "the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10066522", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 841, "text": "the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome, which can discriminate between sequences from different organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Genomic homogeneity is investigated for a broad base of DNA sequences in terms of dinucleotide relative abundance distances (abbreviated delta-distances)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7809131", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 423, "text": "delta-distances between different genomic sequences in the same species are low, only about 2 or 3 times the distance found in random DNA, and are generally smaller than the between-species delta-distances", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7809131", "endSection": "abstract" }, { "offsetInBeginSection": 47, "offsetInEndSection": 160, "text": "the set of dinucleotide odds ratios or 'general design' is a remarkably stable property of the DNA of an organism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 819, "text": "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature', between bacterial chromosomes and plasmids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 601, "text": "The correlation between the genomic signature and DNA-DNA hybridisation values was high and taxa that showed less than 30% DNA-DNA binding will in general not have dinucleotide relative abundance dissimilarity (delta*) values below 40.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15046306", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 476, "text": "Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 488, "text": "Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9294192", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 818, "text": "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or genomic signature, between bacterial chromosomes and plasmids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953039", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 489, "text": "Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9294192", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1127, "text": "We demonstrate that the Mahalanobis distance is better than the delta-distance at measuring genomic signature differences between plasmids and chromosomes of potential hosts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953039", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 824, "text": "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature', between bacterial chromosomes and plasmids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953039", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 823, "text": "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature', between bacterial chromosomes and plasmids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953039", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 476, "text": "Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "endSection": "abstract" } ] }, { "body": "Name a method for enrichment of arginine-methylated peptides.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24129315" ], "ideal_answer": [ "Immunoaffinity purification using specific antibodies has been used in order to perform enrichment of methylated peptides." ], "exact_answer": [ "Immunoaffinity purification" ], "concepts": [ "http://www.biosemantics.org/jochem#4275376", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010455", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001120", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745" ], "type": "factoid", "id": "532206819b2d7acc7e00000f", "snippets": [ { "offsetInBeginSection": 395, "offsetInEndSection": 795, "text": "To better study protein methylation, we have developed highly specific antibodies against monomethyl arginine; asymmetric dimethyl arginine; and monomethyl, dimethyl, and trimethyl lysine motifs. These antibodies were used to perform immunoaffinity purification of methyl peptides followed by LC-MS/MS analysis to identify and quantify arginine and lysine methylation sites in several model studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129315", "endSection": "abstract" } ] }, { "body": "Why do we use \"N-terminal proteomics\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23745983", "http://www.ncbi.nlm.nih.gov/pubmed/19767749", "http://www.ncbi.nlm.nih.gov/pubmed/22065552", "http://www.ncbi.nlm.nih.gov/pubmed/18836177", "http://www.ncbi.nlm.nih.gov/pubmed/20627866", "http://www.ncbi.nlm.nih.gov/pubmed/23964590" ], "ideal_answer": [ "N-terminal proteomics allows the systematic identification of protease/peptidase cleavage events revealing substrate cleavage specificities." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "summary", "id": "5335ebb6d6d3ac6a34000054", "snippets": [ { "offsetInBeginSection": 1183, "offsetInEndSection": 1264, "text": "ChaFRADIC is a powerful and practicable tool for protease and peptidase research,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964590", "endSection": "abstract" }, { "offsetInBeginSection": 46, "offsetInEndSection": 138, "text": "systematic identification of protease cleavage events by quantitative N-terminal proteomics,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20627866", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 783, "text": " identifying the largest set of protein protease substrates ever reported and gaining novel insight into substrate specificity differences of these cathepsins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20627866", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1138, "text": "new insights into the structure-function relationship of protease targets and their validation from large-scale approaches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19767749", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 835, "text": "revealed unknown cleavage specificities, uncharacterized extended specificity profiles, and macromolecular determinants in substrate selection that were confirmed by molecular modeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18836177", "endSection": "abstract" } ] }, { "body": "List omics technologies comprised in system biology.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23294434", "http://www.ncbi.nlm.nih.gov/pubmed/23287290", "http://www.ncbi.nlm.nih.gov/pubmed/26557869", "http://www.ncbi.nlm.nih.gov/pubmed/23369275", "http://www.ncbi.nlm.nih.gov/pubmed/22221061", "http://www.ncbi.nlm.nih.gov/pubmed/23137709", "http://www.ncbi.nlm.nih.gov/pubmed/24957891", "http://www.ncbi.nlm.nih.gov/pubmed/16895927", "http://www.ncbi.nlm.nih.gov/pubmed/23256674" ], "ideal_answer": [ "System biology combines various omics technologies such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, glucomics, degradomics and fluxomics." ], "exact_answer": [ [ "genomics" ], [ "transcriptomics" ], [ "proteomics" ], [ "metabolomics" ], [ "degradomics" ], [ "fluxomics" ], [ "epigenomics" ], [ "glucomics" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049490" ], "type": "list", "id": "56d29d4df22319765a000003", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 170, "text": "The increasing role of metabolomics in system biology is driving the development of tools for comprehensive analysis of high-resolution NMR spectral datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16895927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Proteomics technology, a major component of system biology, has gained comprehensive attention in the area of medical diagnosis, drug development, and mechanism research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26557869", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 441, "text": "Metabolomics complements other omics, such as transcriptomics and proteomics and since it is a 'downstream' result of gene expression, changes in the metabolome is considered to best reflect the activities of the cell at a functional level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23369275", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 903, "text": "In addition, integrated applications with genomics, transcriptomics, and proteomics provide greater understanding of global system biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23369275", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 73, "text": "From proteomics to integrated omics towards system biology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23137709", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "In recent years, in the post genomic era, more and more data is being generated by biological high throughput technologies, such as proteomics and transcriptomics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23294434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Glycomics meets genomics, epigenomics and other high throughput omics for system biology studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23287290", "endSection": "title" }, { "offsetInBeginSection": 634, "offsetInEndSection": 782, "text": "The current state-of-the-art in high-throughput glycomics and its integration with genomics, epigenomics and lipidomics is reviewed in this article.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23287290", "endSection": "abstract" }, { "offsetInBeginSection": 889, "offsetInEndSection": 1039, "text": "The resulting lists of metabolites and their steady state concentrations in combination with transcriptomics can be used in system biology approaches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24957891", "endSection": "abstract" }, { "offsetInBeginSection": 921, "offsetInEndSection": 1030, "text": "all system biology aspects (genomics, transcriptomics, proteomics, metabolomics, degradomics and fluxomics). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23256674", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 671, "text": "Recent development in high-throughput methods enables analysis of genome, transcriptome, proteome, and metabolome at an unprecedented scale, thus contributing to the deluge of experimental data in numerous public databases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22221061", "endSection": "abstract" } ] }, { "body": "Rindopepimut is an analog of which growth factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25186601", "http://www.ncbi.nlm.nih.gov/pubmed/23055947", "http://www.ncbi.nlm.nih.gov/pubmed/22309662", "http://www.ncbi.nlm.nih.gov/pubmed/21154166" ], "ideal_answer": [ "Rindopepimut is an analog of EGFRvIII. It is being tested for treatment of glioblastoma multiforme", "Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. " ], "exact_answer": [ "EGFRvIII" ], "concepts": [ "http://www.uniprot.org/uniprot/GRFA_CAMPM", "http://www.uniprot.org/uniprot/GRFA_RFVKA", "http://www.uniprot.org/uniprot/GRFA_RABPU", "http://www.uniprot.org/uniprot/GRFA_MYXVL", "http://www.uniprot.org/uniprot/GRFA_CAMPS" ], "type": "factoid", "id": "54d8fd334b1fd0d33c000005", "snippets": [ { "offsetInBeginSection": 600, "offsetInEndSection": 829, "text": "Rindopepimut consists of a 14-mer peptide that spans the length of EGF receptor variant III, a mutant variant of EGF receptor found on approximately 30% of primary GBM, conjugated to the carrier protein keyhole limpet hemocyanin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25186601", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 645, "text": "Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055947", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 731, "text": "A peptide vaccine, rindopepimut (CDX-110, Celldex Therapeutics), is directed against the novel exon 1-8 junction produced by the EGFRvIII deletion, and it has shown high efficacy in preclinical models. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22309662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Rindopepimut, a 14-mer injectable peptide vaccine against EGFRvIII for the potential treatment of glioblastoma multiforme.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21154166", "endSection": "title" }, { "offsetInBeginSection": 157, "offsetInEndSection": 365, "text": "Rindopepimut specifically targets a novel junctional epitope of the EGFR deletion mutant EGFRvIII, which is a constitutively active receptor that is expressed in approximately 60 to 70% of patients with GBM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21154166", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 729, "text": "A peptide vaccine, rindopepimut (CDX-110, Celldex Therapeutics), is directed against the novel exon 1-8 junction produced by the EGFRvIII deletion, and it has shown high efficacy in preclinical models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22309662", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 643, "text": "Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055947", "endSection": "abstract" } ] }, { "body": "Which gene mutations are responsible for isolated Non-compaction cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21285074", "http://www.ncbi.nlm.nih.gov/pubmed/18159245", "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "http://www.ncbi.nlm.nih.gov/pubmed/19438153", "http://www.ncbi.nlm.nih.gov/pubmed/14662268", "http://www.ncbi.nlm.nih.gov/pubmed/21604106", "http://www.ncbi.nlm.nih.gov/pubmed/20083571", "http://www.ncbi.nlm.nih.gov/pubmed/20542340", "http://www.ncbi.nlm.nih.gov/pubmed/21551322", "http://www.ncbi.nlm.nih.gov/pubmed/20386670", "http://www.ncbi.nlm.nih.gov/pubmed/23314057", "http://www.ncbi.nlm.nih.gov/pubmed/23074372", "http://www.ncbi.nlm.nih.gov/pubmed/18395448", "http://www.ncbi.nlm.nih.gov/pubmed/17101628", "http://www.ncbi.nlm.nih.gov/pubmed/22619057", "http://www.ncbi.nlm.nih.gov/pubmed/23800289", "http://www.ncbi.nlm.nih.gov/pubmed/19467449", "http://www.ncbi.nlm.nih.gov/pubmed/19028670", "http://www.ncbi.nlm.nih.gov/pubmed/22859017", "http://www.ncbi.nlm.nih.gov/pubmed/17956225", "http://www.ncbi.nlm.nih.gov/pubmed/24015429", "http://www.ncbi.nlm.nih.gov/pubmed/21894393", "http://www.ncbi.nlm.nih.gov/pubmed/21789513", "http://www.ncbi.nlm.nih.gov/pubmed/17947214" ], "ideal_answer": [ "The gene mutations that have been shown to be the causes of isolated non-compaction cardiomyopathy are alpha-tropomyosin, alpha-tropomyosin, troponin T and desmoplakin", "cardiac \u03b2-myosin heavy chain gene (MYH7)\nc.349G>A (p.D117N) in the ZASP gene\nmutation in the isoform-1 specific region of the DSP C-terminus\npE96K mutation in the cardiac troponin T gene (TNNT2)" ], "exact_answer": [ [ "alpha-tropomyosin", "TPM1" ], [ "\u03b2-myosin heavy chain", "MYH7" ], [ "troponin T", "TNNT2", "pE96K mutation" ], [ "Desmoplakin", "DSP", "mutation in the isoform-1 specific region of the DSP C-terminus" ], [ "mindbomb homolog 1", "MIB1" ], [ "c.349G>A (p.D117N) in the ZASP gene" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056830", "http://www.disease-ontology.org/api/metadata/DOID:0050700" ], "type": "list", "id": "52ea605098d0239505000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "A novel alpha-tropomyosin mutation associates with dilated and non-compaction cardiomyopathy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "endSection": "title" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1418, "text": "We show that a mutation in TPM1 is associated with DCM and a lethal, early onset form of NCCM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1105, "text": "Mutation in MYH7B causes a classical LVNC phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23800289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "We report on two prenatal ultrasound diagnoses of left ventricular non-compaction cardiomyopathy (LVNC) associated with mutation of the cardiac \u03b2-myosin heavy chain gene (MYH7)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859017", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 972, "text": "This novel homozygous truncating mutation in the isoform-1 specific region of the DSP C-terminus caused Carvajal syndrome comprising severe early-onset heart failure with features of non-compaction cardiomyopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Severe familial left ventricular non-compaction cardiomyopathy due to a novel troponin T (TNNT2) mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20083571", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 391, "text": "we describe a family with LVNC due to a novel missense mutation, pE96K, in the cardiac troponin T gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20083571", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 800, "text": "We describe, in two separate autosomal-dominant NCCM families, the identification of mutations in the sarcomeric cardiac beta-myosin heavy chain gene (MYH7)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17947214", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1109, "text": "the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17947214", "endSection": "abstract" } ] }, { "body": "From which tissue was the NCI-H520 cell-line derived?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20219072", "http://www.ncbi.nlm.nih.gov/pubmed/8822090", "http://www.ncbi.nlm.nih.gov/pubmed/23489803", "http://www.ncbi.nlm.nih.gov/pubmed/12702576", "http://www.ncbi.nlm.nih.gov/pubmed/14965369", "http://www.ncbi.nlm.nih.gov/pubmed/15750352", "http://www.ncbi.nlm.nih.gov/pubmed/12964003", "http://www.ncbi.nlm.nih.gov/pubmed/9099905", "http://www.ncbi.nlm.nih.gov/pubmed/16798224", "http://www.ncbi.nlm.nih.gov/pubmed/16820889", "http://www.ncbi.nlm.nih.gov/pubmed/14586397", "http://www.ncbi.nlm.nih.gov/pubmed/16462760", "http://www.ncbi.nlm.nih.gov/pubmed/12851688", "http://www.ncbi.nlm.nih.gov/pubmed/16549820", "http://www.ncbi.nlm.nih.gov/pubmed/17600088", "http://www.ncbi.nlm.nih.gov/pubmed/14720367", "http://www.ncbi.nlm.nih.gov/pubmed/18223678", "http://www.ncbi.nlm.nih.gov/pubmed/16877704", "http://www.ncbi.nlm.nih.gov/pubmed/23715514", "http://www.ncbi.nlm.nih.gov/pubmed/19968287", "http://www.ncbi.nlm.nih.gov/pubmed/11830536", "http://www.ncbi.nlm.nih.gov/pubmed/22562359", "http://www.ncbi.nlm.nih.gov/pubmed/19700217", "http://www.ncbi.nlm.nih.gov/pubmed/9492037", "http://www.ncbi.nlm.nih.gov/pubmed/15007389", "http://www.ncbi.nlm.nih.gov/pubmed/15254679", "http://www.ncbi.nlm.nih.gov/pubmed/18502124", "http://www.ncbi.nlm.nih.gov/pubmed/9616291", "http://www.ncbi.nlm.nih.gov/pubmed/24040647", "http://www.ncbi.nlm.nih.gov/pubmed/12680874", "http://www.ncbi.nlm.nih.gov/pubmed/11598125" ], "ideal_answer": [ "Non-small cell lung cancer (NSCLC) cell line NCI-H520. \nSquamous cell carcinoma cell line NCI-H520.", "The NCI-H520 cell-line is derived from human non-small cell lung cancer tissue." ], "exact_answer": [ "Squamous cell carcinoma", "Non-small cell lung cancer", "Lung" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002460", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014024", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045744", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054547" ], "type": "factoid", "id": "52f89fc62059c6d71c000050", "snippets": [ { "offsetInBeginSection": 509, "offsetInEndSection": 841, "text": "The nanostructures target the cells with high affinity and specificity via the specific interaction between the aptamer (a 45-base oligonucleotide) and the cell, and distinguish A549 cells from other types of cancer cells (HeLa and MCF-7 cells) and subtypes of lung cancer cells (NCI-H157, NCI-H520, NCI-H1299, and NCI-H446 cells). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040647", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 609, "text": "Functional studies in A549 bronchioalveolar carcinoma and NCI-H520 squamous cell carcinoma cells revealed that Msi1 was enriched in spheroid cultures of tumor cells and in the CD133+ cell population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23715514", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 383, "text": "BHLHB3 gene overexpression inhibited colony formation of A549, NCI-H520 and NCI-H596 lung cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18223678", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 738, "text": "Cellular proliferation was inhibited in non-small cell lung cancer (NSCLC) cell lines NCI-H460, NCI-H520, NCI-H1299, and SK-MES-1 by CTGF overexpression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16877704", "endSection": "abstract" }, { "offsetInBeginSection": 1113, "offsetInEndSection": 1210, "text": "Human NCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased colony-forming ability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16549820", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1024, "text": "In 4 lung cancer cell strains, BNIP3L protein was not detected in A549, NCI-H460, NCI-H446, except for NCI-H520, in which the protein expression level was slightly lower than that in immortal bronchial epithelial cell strain HBE4-E6/E7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14720367", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1139, "text": "We show that CLN3 mRNA and protein are overexpressed in glioblastoma (U-373G and T98g), neuroblastoma (IMR-32 and SK-N-MC), prostate (Du145, PC-3, and LNCaP), ovarian (SK-OV-3, SW626, and PA-1), breast (BT-20, BT-549, and BT-474), and colon (SW1116, SW480, and HCT 116) cancer cell lines but not in pancreatic (CAPAN and As-PC-1) or lung (A-549 and NCI-H520) cancer cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11830536", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 659, "text": "NSCLC cell lines NCI-H520 and H460, which have no endogenous Cyr61, formed 60-90% fewer colonies after being transfected with a Cyr61 cDNA expression vector than cells transfected with the same amount of empty vector.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11598125", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1249, "text": "Importantly, the non-small cell lung carcinoma cell lines expressed either liver-specific (non-neuronal) mRNA (cell line A549) or predominantly the neuronal (cell line NCI-H520) AADC message. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9616291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The antitumor effect of CGP41251 (4'-N-benzoyl staurosporine), a selective protein kinase C (PKC) inhibitor, was examined on two kinds of human non-small cell lung cancer (NSCLC) cell lines (adenocarcinoma: A549 and squamous cell carcinoma: NCI-H520).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8822090", "endSection": "abstract" } ] }, { "body": "Have mutations in the Polycomb group been found in human diseases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22869879", "http://www.ncbi.nlm.nih.gov/pubmed/22190018", "http://www.ncbi.nlm.nih.gov/pubmed/23418308", "http://www.ncbi.nlm.nih.gov/pubmed/20506229", "http://www.ncbi.nlm.nih.gov/pubmed/18668134", "http://www.ncbi.nlm.nih.gov/pubmed/16397222", "http://www.ncbi.nlm.nih.gov/pubmed/16575874", "http://www.ncbi.nlm.nih.gov/pubmed/22328940", "http://www.ncbi.nlm.nih.gov/pubmed/23204235", "http://www.ncbi.nlm.nih.gov/pubmed/16963837", "http://www.ncbi.nlm.nih.gov/pubmed/22237151", "http://www.ncbi.nlm.nih.gov/pubmed/19904743", "http://www.ncbi.nlm.nih.gov/pubmed/22431509", "http://www.ncbi.nlm.nih.gov/pubmed/21921040" ], "ideal_answer": [ "Yes, different members of the Polycomb family have been found mutated in diseases such as primary microcephaly, nonsyndromic cleft lip and several cancers (including hemotopoietic malignancies, esophageal carcinoma, head and neck cancer or prostate cancer).\n\nExact anser:\nYes" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/PC_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031519" ], "type": "yesno", "id": "5176c6d08ed59a060a000032", "snippets": [ { "offsetInBeginSection": 543, "offsetInEndSection": 831, "text": "We identify a novel mutation in PHC1, a human orthologue of the Drosophila polyhomeotic member of polycomb group (PcG), which significantly decreases PHC1 protein expression, increases Geminin protein level and markedly abolishes the capacity to ubiquitinate histone H2A in patient cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23418308", "endSection": "sections.0" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1407, "text": "In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204235", "endSection": "sections.0" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1413, "text": "Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22869879", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "In this study, we show the high frequency of spontaneous \u03b3\u03b4 T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431509", "endSection": "sections.0" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1237, "text": "Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190018", "endSection": "sections.0" }, { "offsetInBeginSection": 273, "offsetInEndSection": 434, "text": "A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21921040", "endSection": "sections.0" }, { "offsetInBeginSection": 326, "offsetInEndSection": 732, "text": "In the present investigation we have focused on the candidate region in 6p23, a region that have been found linked to CL/P in several investigations, in the attempt to find out the susceptibility gene provisionally named OFC1. Gene expression experiments in mice embryo of positional candidate genes revealed that JARID2 was highly and specifically expressed in epithelial cells in merging palatal shelves.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20506229", "endSection": "sections.0" }, { "offsetInBeginSection": 558, "offsetInEndSection": 660, "text": "High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19904743", "endSection": "sections.0" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1256, "text": "We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18668134", "endSection": "sections.0" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1378, "text": "We demonstrate that in multiple experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are amplified and gene amplification is associated with increased expression of corresponding mRNAs and proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963837", "endSection": "sections.0" }, { "offsetInBeginSection": 1512, "offsetInEndSection": 1618, "text": "he EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575874", "endSection": "sections.0" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1222, "text": "The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16397222", "endSection": "sections.0" } ] }, { "body": "Describe the mechanism of action of drisapersen", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25209738", "http://www.ncbi.nlm.nih.gov/pubmed/24321374", "http://www.ncbi.nlm.nih.gov/pubmed/24620745", "http://www.ncbi.nlm.nih.gov/pubmed/24292388", "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "http://www.ncbi.nlm.nih.gov/pubmed/24229740" ], "ideal_answer": [ "Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. It has potential for treatment of Duchenne muscular dystrophy." ], "type": "summary", "id": "54fc98f16ad7dcbc12000003", "snippets": [ { "offsetInBeginSection": 167, "offsetInEndSection": 319, "text": "Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "UNLABELLED: Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292388", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 646, "text": "Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 610, "text": "Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 317, "text": "Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321374", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 664, "text": "Fast forward 25 years, and two phase 2b/3 trials have been carried out with agents designed to induce de novo dystrophin production in DMD patient's muscle; ataluren (stop codon read through) with 174 patients, and drisapersen (exon skipping) with 186 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24229740", "endSection": "abstract" } ] }, { "body": "Is microRNA(miRNA) 29 involved in post-ischemic cardiac remodeling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20971881", "http://www.ncbi.nlm.nih.gov/pubmed/20959496", "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "http://www.ncbi.nlm.nih.gov/pubmed/20733099", "http://www.ncbi.nlm.nih.gov/pubmed/18723672" ], "ideal_answer": [ "miRNA 29 is involved in post-ischemic myocardial remodeling in particular in the peri-infarctual zone. miRNA 29 produces apoptosis and enhances fibrotic response." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0035196", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010586", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010587", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "yesno", "id": "513f4025bee46bd34c000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. I", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "endSection": "sections.0" }, { "offsetInBeginSection": 590, "offsetInEndSection": 754, "text": "In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "endSection": "sections.0" }, { "offsetInBeginSection": 756, "offsetInEndSection": 813, "text": "Myocardial fibrosis can be regulated by the miR-29 family", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "endSection": "sections.0" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1053, "text": "Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20959496", "endSection": "sections.0" }, { "offsetInBeginSection": 620, "offsetInEndSection": 1357, "text": "Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18723672", "endSection": "sections.0" } ] }, { "body": "What is the incidence of Edwards syndrom in the european population?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19911411", "http://www.ncbi.nlm.nih.gov/pubmed/18467377", "http://www.ncbi.nlm.nih.gov/pubmed/20584846", "http://www.ncbi.nlm.nih.gov/pubmed/18067809", "http://www.ncbi.nlm.nih.gov/pubmed/18156713", "http://www.ncbi.nlm.nih.gov/pubmed/21786507", "http://www.ncbi.nlm.nih.gov/pubmed/23421080", "http://www.ncbi.nlm.nih.gov/pubmed/19408854", "http://www.ncbi.nlm.nih.gov/pubmed/8248469", "http://www.ncbi.nlm.nih.gov/pubmed/23116348" ], "ideal_answer": [ "Between 0.125 and 39 in every 1000 live births. Most probably 1:5000 of live-born." ], "exact_answer": [ "1:5000" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015994", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014314", "http://www.disease-ontology.org/api/metadata/DOID:1085" ], "type": "factoid", "id": "52f350042059c6d71c000010", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 102, "text": "dwards syndrome (trisomy 18) occurs in 1: 8000 live births and is closely related to the mother's age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23421080", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1274, "text": "Mean incidence was 390.06 (449.08 in boys and 327.93 in girls) per 10 000 live births", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116348", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 396, "text": "The incidence of Edwards syndrome is 1:5000 of live-born", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21786507", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1310, "text": "The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); and for XYY syndrome, 1.99 (0.75 to 5.26)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20584846", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 937, "text": "The live birth prevalence in the absence of prenatal screening and selective termination in England and Wales from 1997 to 2004 was 1.4 (95% CI: 1.2-1.6) per 10 000 births for trisomy 13 and 2.3 (95% CI: 2.1-2.5) for trisomy 18", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19911411", "endSection": "abstract" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1997, "text": "During the period under the study, following total numbers, mean relative incidences (per 10,000 live births, in brackets) and mean prenatal diagnostics efficiency (in %) were found in following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19408854", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1278, "text": "There was evidence of space-time clustering for Down syndrome (fixed threshold of close in space: P = 0.01, NN threshold: P = 0.02), but little or no clustering for Patau (P = 0.57, P = 0.19) or Edwards (P = 0.37, P = 0.06) syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467377", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 836, "text": "Of the 49,806 pregnant women between 15 and 23 weeks' gestational age who received prenatal serum screening with a cut-off value (a risk of 1:270 for Down and 1:100 for Edwards syndrome), 2,116 (4.2%) and 196 (0.4%) were screen positive for Down syndrome and for Edwards syndrome, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18156713", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1265, "text": "26,803 of the 27,313 women (98%) were screened. The average was 25.1, and 1.7% of them were over 35. Serum screening showed that 1,244 (5%) were Down syndrome positive and 105 (0.4%) were Edwards syndrome positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18067809", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 728, "text": "235 pregnancies of women delivered in units in the North West Thames region over a two-year period (1990-91) whose babies or fetuses were diagnosed as having Down, Edwards or Patau syndrome. RESULTS: 33% of Down syndrome, 68% of Edwards syndrome and 52% of Patau syndrome were diagnosed prenatally (before 28 weeks) in the region without the use of serum screening. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8248469", "endSection": "abstract" } ] }, { "body": "Is exonuclease Xrn1 a component of the P-bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19729507", "http://www.ncbi.nlm.nih.gov/pubmed/17923231", "http://www.ncbi.nlm.nih.gov/pubmed/16299471", "http://www.ncbi.nlm.nih.gov/pubmed/22383165", "http://www.ncbi.nlm.nih.gov/pubmed/20011505", "http://www.ncbi.nlm.nih.gov/pubmed/17178403", "http://www.ncbi.nlm.nih.gov/pubmed/18652574", "http://www.ncbi.nlm.nih.gov/pubmed/22590546", "http://www.ncbi.nlm.nih.gov/pubmed/16177138", "http://www.ncbi.nlm.nih.gov/pubmed/22056521", "http://www.ncbi.nlm.nih.gov/pubmed/23756462", "http://www.ncbi.nlm.nih.gov/pubmed/20962086", "http://www.ncbi.nlm.nih.gov/pubmed/23102969", "http://www.ncbi.nlm.nih.gov/pubmed/19091970", "http://www.ncbi.nlm.nih.gov/pubmed/21859862", "http://www.ncbi.nlm.nih.gov/pubmed/15901504", "http://www.ncbi.nlm.nih.gov/pubmed/20074068", "http://www.ncbi.nlm.nih.gov/pubmed/23892092" ], "ideal_answer": [ "In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' \u2192 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place. Many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3.", "In eukaryotic cells, degradation of bulk mRNA in the 5' to 3' direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 5' to 3' exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies.", "We show that the RNA-binding protein GW182 and the DCP1:DCP2 decapping complex are required for miRNA-mediated gene silencing, uncovering a crucial role for P-body components in the miRNA pathway. An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. Our results show that mammalian cells, similar to yeast, require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs. Recent evidence suggests that the processing bodies may constitute specialized cellular compartments of mRNA turnover, which suggests that mRNA and protein localization may be integral to mRNA decay." ], "exact_answer": "yes", "type": "yesno", "id": "56c9e9d15795f9a73e00001d", "snippets": [ { "offsetInBeginSection": 909, "offsetInEndSection": 1246, "text": "PBs are associated with mRNA decay and contain the decapping enzymes DCP1/2, the 5' to 3' exonuclease Xrn1, the Lsm proteins (1-7), and the scaffolding proteins hedls/GE-1 and GW182. Both SGs and PBs contain mRNA, eIF4E, microRNAs and argonaute proteins, and various regulators of mRNA stability and translation (TTP, RCK/p54, and CPEB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17923231", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 555, "text": "An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16299471", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 328, "text": "n eukaryotic cells degradation of bulk mRNA in the 5' to 3' direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 5' to 3' exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies or GW-bodies (because of the accumulation of the GW182 antigen).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16177138", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 718, "text": "Several proteins that stimulate mRNA decapping by the Dcp1:Dcp2 complex co-localize with Dcp1 and Dcp2, together with Xrn1, a 5'-to-3' exonuclease, to structures in the cytoplasm called processing bodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15901504", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 538, "text": " On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23102969", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1121, "text": "We identified the Pab 1801 cytoplasmic puncta as P Bodies (PBs), which are involved in mRNA regulation. We found that, in several cell lines, including U2OS, WI38, SK-N-SH and HCT116, the Pab 1801 puncta strictly colocalize with PBs identified with specific antibodies against the PB components Hedls, Dcp1a, Xrn1 or Rck/p54.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22590546", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 732, "text": "The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056521", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1326, "text": "The second type of granules, piP-bodies, harbors the MIWI2-TDRD9-MAEL module of the piRNA pathway and signature components of P-bodies, GW182, DCP1a, DDX6/p54, and XRN1 proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20011505", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 440, "text": "In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18652574", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 581, "text": "Here, we show that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic \"P bodies,\" including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression (Dhh1p/Me31B) pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17178403", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 793, "text": " In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' \u2192 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383165", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 449, "text": "In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18652574", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 566, "text": "Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23892092", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 741, "text": "The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056521", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 590, "text": "Here, we show that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic "P bodies," including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression (Dhh1p/Me31B) pathways", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17178403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23102969", "endSection": "title" }, { "offsetInBeginSection": 488, "offsetInEndSection": 880, "text": "The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated. Various growth conditions, including glucose deprivation, hyperosmotic stress, and heat stress, stimulated the accumulation of P-bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056521", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 539, "text": "Here we show that microscopically visible P-bodies are greatly diminished following West Nile viral infection, but the component proteins are not depleted. On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23102969", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 775, "text": "Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71. Computational analyses of non-synonymous SNPs of these components was initiated using well utilized publicly available software programs such as the SIFT, followed by PolyPhen, PANTHER, MutPred, I-Mutant-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23892092", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 384, "text": "Xrn1 has been shown to be a component of P-bodies (processing bodies),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18652574", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 601, "text": "Here, we show that hDIS3L2 is an exosome-independent cytoplasmic mRNA 3'-5' exonuclease, which exhibits processive activity on structured RNA substrates in vitro. hDIS3L2 associates with hXRN1 in an RNA-dependent manner and can, like hXRN1, be found on polysomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23756462", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 670, "text": "Inhibition of TAK1-JNK signaling also affected the number and size of P bodies and the localization of DCP1a, Xrn1, and Edc4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21859862", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1298, "text": " The organizing mechanism that forms P body foci in cells is unknown; however, potential scaffolding, aggregating, or other regulatory proteins found in P bodies were investigated for degradation. Two factors involved in 5'-end mRNA decapping and degradation, Xrn1 and Dcp1a, and the 3' deadenylase complex component Pan3 underwent accelerated degradation during infection, and Dcp1a may be a direct substrate of PV 3C proteinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20962086", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 543, "text": "Secondly, P-bodies recruit mRNAs that are targeted for deadenylation and degradation by the decapping/Xrn1 pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074068", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1053, "text": "Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5'-3' exonuclease Xrn1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19729507", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 595, "text": "In this paper we show for the first time that Pacman, the Drosophila homologue of Xrn1, is localized in cytoplasmic particles in Drosophila testis cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18652574", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1062, "text": "Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5'-3' exonuclease Xrn1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19729507", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 849, "text": "These structures stain positively for a number of P-body and microRNP components, a microRNA-repressed mRNA and some translational repressors. They appear more heterogeneous than P-bodies of HeLa cells, and they rarely contain the exonuclease Xrn1 but are positive for rRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19091970", "endSection": "abstract" } ] }, { "body": "What is the substrate of the microbial enzyme inulinase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22622836", "http://www.ncbi.nlm.nih.gov/pubmed/18592410", "http://www.ncbi.nlm.nih.gov/pubmed/22286980", "http://www.ncbi.nlm.nih.gov/pubmed/23419675", "http://www.ncbi.nlm.nih.gov/pubmed/23997327", "http://www.ncbi.nlm.nih.gov/pubmed/17659392", "http://www.ncbi.nlm.nih.gov/pubmed/18065000", "http://www.ncbi.nlm.nih.gov/pubmed/17005986", "http://www.ncbi.nlm.nih.gov/pubmed/23265469", "http://www.ncbi.nlm.nih.gov/pubmed/19256341", "http://www.ncbi.nlm.nih.gov/pubmed/23271628", "http://www.ncbi.nlm.nih.gov/pubmed/18663416", "http://www.ncbi.nlm.nih.gov/pubmed/24031675", "http://www.ncbi.nlm.nih.gov/pubmed/18427804", "http://www.ncbi.nlm.nih.gov/pubmed/24031804", "http://www.ncbi.nlm.nih.gov/pubmed/19107534", "http://www.ncbi.nlm.nih.gov/pubmed/18449567", "http://www.ncbi.nlm.nih.gov/pubmed/18833660", "http://www.ncbi.nlm.nih.gov/pubmed/18726619", "http://www.ncbi.nlm.nih.gov/pubmed/20597549", "http://www.ncbi.nlm.nih.gov/pubmed/19514896", "http://www.ncbi.nlm.nih.gov/pubmed/22629216", "http://www.ncbi.nlm.nih.gov/pubmed/18051293" ], "ideal_answer": [ "The inulinase acts on the beta-(2,1)-D-fructoside links in inulin releasing D-fructose." ], "exact_answer": [ "The inulinase acts on the beta-(2,1)-D-fructoside links in inulin releasing D-fructose." ], "concepts": [ "http://www.uniprot.org/uniprot/INU2_ASPFI", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051670", "http://www.uniprot.org/uniprot/INU1_KLUMA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013379" ], "type": "factoid", "id": "54f60ae05f206a0c06000008", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 269, "text": "Inulinases mainly produced by the microorganism and it degrades inulin into fructose which is a digestible form. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997327", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 502, "text": " Inulin or inulin-rich materials can be actively hydrolyzed by microbial inulinases to produce glucose and fructose syrups that can be used in bioprocesses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419675", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 732, "text": " The catalysts treated at these conditions in both fluids were then used for the production of fructooligosaccharides (FOS) using sucrose and inulin as substrates in aqueous and organic systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23271628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "This work is focused on the synthesis of the fructooligosaccharides (FOS) from sucrose and inulin, using free, immobilized and pre-treated immobilized inulinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23265469", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 913, "text": "Using inulinases from K. marxianus NRRL Y 7571, 11.89% of GF2 and 20.83% of GF3 were obtained, using inulin as substrate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23265469", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1050, "text": "TLC analysis of end product revealed that inulinase hydrolyzed inulin exclusively into fructose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24031804", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 357, "text": "One product was an endo-inulinase, and the other was a \u03b2-fructofuranosidase. Both enzymes worked together to effectively degrade inulin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22286980", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 317, "text": "The K (m) and V (max) values of the purified enzyme for inulin were 2.3 mg/mL and 4.8 mg/min, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22622836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Fructans were extracted from Agave salmiana juice, characterized and subjected to hydrolysis process using a commercial inulinase preparation acting freely. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22629216", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1095, "text": "A comparatively lower Michaelis-Menten constant (2.15 mg/ml) and higher maximum initial velocity (115 \u00b5mol/min/mg of protein) for inulinase I on inulin demonstrated the exoinulinase's greater affinity for inulin substrate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24031675", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 432, "text": "Inulin was hydrolyzed by the purified enzyme, yielding d-fructose as the main product. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20597549", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 681, "text": "The inulinase acts on the beta-(2,1)-D-fructoside links in inulin releasing D-fructose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19514896", "endSection": "abstract" } ] }, { "body": "What is the treatment of acute myocarditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19214293", "http://www.ncbi.nlm.nih.gov/pubmed/11477833", "http://www.ncbi.nlm.nih.gov/pubmed/17622371", "http://www.ncbi.nlm.nih.gov/pubmed/17574515", "http://www.ncbi.nlm.nih.gov/pubmed/12055771", "http://www.ncbi.nlm.nih.gov/pubmed/20034334", "http://www.ncbi.nlm.nih.gov/pubmed/20207278" ], "ideal_answer": [ "Treatment of acute myocarditis includes antiinflammatory drugs like ibuoprofen and steroids, inotropic agents and mechanical support (intra-aortic ballon pump). TandemHeart percutaneous ventricular assist device may be used in some, more compromised, patients for few days." ], "exact_answer": [ [ "antiinflammatory steroid and non steroid drugs" ], [ "inotropic agents" ], [ "mechanical support" ] ], "type": "list", "id": "517a8cc68ed59a060a000044", "snippets": [ { "offsetInBeginSection": 2394, "offsetInEndSection": 2433, "text": "ibuprofen 400 mg twice a day as therapy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20034334", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Acute fulminant myocarditis commonly manifests itself as severe, rapidly progressive hemodynamic deterioration and circulatory collapse that may be resistant to high doses of inotropic agents and steroids and to mechanical support by intra-aortic balloon pump", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17622371", "endSection": "sections.0" }, { "offsetInBeginSection": 478, "offsetInEndSection": 579, "text": "the TandemHeart percutaneous ventricular assist device, can enable patients to recover in a few days.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17622371", "endSection": "sections.0" }, { "offsetInBeginSection": 477, "offsetInEndSection": 642, "text": "he authors report a typical case of fulminating myocarditis with electromechanical dissociation, which recovered completely after a period of circulatory assistance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12055771", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 161, "text": "To clarify the effects of Astragalus Membranaceus (AM) combined with taurine and/or coenzyme Q10(CoQ10) on coxsackievirus B3 (CVB3) murine myocarditis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11477833", "endSection": "sections.0" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1001, "text": "AM, taurine and CoQ10 have some curative effects on CVB3 murine myocarditis, AM combined with taurine and CoQ10 is the best.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11477833", "endSection": "sections.0" } ] }, { "body": "List causative genes for autosomal recessive forms of monogenic Parkinson's disease", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24167038", "http://www.ncbi.nlm.nih.gov/pubmed/18787878", "http://www.ncbi.nlm.nih.gov/pubmed/11128611", "http://www.ncbi.nlm.nih.gov/pubmed/15525661", "http://www.ncbi.nlm.nih.gov/pubmed/15917645", "http://www.ncbi.nlm.nih.gov/pubmed/18279377", "http://www.ncbi.nlm.nih.gov/pubmed/17713120", "http://www.ncbi.nlm.nih.gov/pubmed/24244333", "http://www.ncbi.nlm.nih.gov/pubmed/12446870", "http://www.ncbi.nlm.nih.gov/pubmed/10072423", "http://www.ncbi.nlm.nih.gov/pubmed/16003110", "http://www.ncbi.nlm.nih.gov/pubmed/18175395", "http://www.ncbi.nlm.nih.gov/pubmed/19168133", "http://www.ncbi.nlm.nih.gov/pubmed/21626549", "http://www.ncbi.nlm.nih.gov/pubmed/14712351", "http://www.ncbi.nlm.nih.gov/pubmed/19297401", "http://www.ncbi.nlm.nih.gov/pubmed/11911988", "http://www.ncbi.nlm.nih.gov/pubmed/22166400", "http://www.ncbi.nlm.nih.gov/pubmed/17704838", "http://www.ncbi.nlm.nih.gov/pubmed/11261251", "http://www.ncbi.nlm.nih.gov/pubmed/22166450", "http://www.ncbi.nlm.nih.gov/pubmed/17713119", "http://www.ncbi.nlm.nih.gov/pubmed/22427796", "http://www.ncbi.nlm.nih.gov/pubmed/20696312", "http://www.ncbi.nlm.nih.gov/pubmed/11487197" ], "ideal_answer": [ "Causative genes for autosomal recessive forms of monogenic Parkinson's disease are:\nPARK2\nPARK7\nPINK1\nPARK9\nPARK14\nPARK15" ], "exact_answer": [ [ "PARK2" ], [ "PARK7", "DJ-1" ], [ "PINK1" ], [ "PARK9", "ATP13A2" ], [ "PARK14", "PLA2G6" ], [ "PARK15", "FBX07" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.disease-ontology.org/api/metadata/DOID:0050737", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030849", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.disease-ontology.org/api/metadata/DOID:14330", "http://www.disease-ontology.org/api/metadata/DOID:0050177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300" ], "type": "list", "id": "5318367cb166e2b806000012", "snippets": [ { "offsetInBeginSection": 295, "offsetInEndSection": 400, "text": "Mutations in the Parkin gene (PARK2) are the major cause of autosomal recessive early-onset parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244333", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 327, "text": "Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Homozygous or compound heterozygous mutations in the phosphatase and tensin homolog-induced putative kinase 1 (PINK1) gene are causative of autosomal recessive, early onset Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24167038", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1293, "text": "Mutations in other genes, including ATP13A2 (PARK9), PLA2G6 (PARK14), and FBX07 (PARK15), cause more rare forms of recessive parkinsonism with very early-onset (<30 years)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22166450", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 147, "text": "In three forms, caused by mutations in parkin (PARK2), PINK1 (PARK6), or DJ-1 (PARK7),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22166450", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 615, "text": "oss-of-function mutations in Parkin, PINK1, DJ-1 and ATP13A2 cause autosomal recessive parkinsonism with early-onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297401", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 716, "text": "mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 all cause autosomal-recessive parkinsonism of early onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19168133", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 661, "text": "mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 cause autosomal recessive parkinsonism of early onset", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18787878", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 592, "text": "Mutations in the parkin gene, in DJ-1 and PINK1 all cause autosomal recessive parkinsonism of early onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18175395", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "PTEN-induced putative kinase 1 (PINK1) is a causative gene for autosomal recessive early onset parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17713119", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 415, "text": " we focus on PARK7, a gene relates to an autosomal recessive form of early-onset Parkinsonism and encodes a protein named DJ-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17704838", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 908, "text": "PINK-1 for an autosomal-recessive early-onset variant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003110", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 244, "text": " Heritable mutations in alpha-synuclein, parkin, DJ-1 and PINK1 cause familial forms of PD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15525661", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 284, "text": "we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14712351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12446870", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Autosomal recessive parkinsonism associated with mutations in the parkin gene represents a monogenic form of hereditary parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11911988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11487197", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1336, "text": " A gene causing autosomal recessive parkinsonism of juvenile onset has been mapped to chromosome 6 (PARK 2), and the causative gene has been identified and named parkin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11128611", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 362, "text": "The gene responsible for AR-JP was recently identified and designated parkin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10072423", "endSection": "abstract" } ] }, { "body": "How does ranolazine affect calcium handling in the heart", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21741479", "http://www.ncbi.nlm.nih.gov/pubmed/17027025", "http://www.ncbi.nlm.nih.gov/pubmed/18439620", "http://www.ncbi.nlm.nih.gov/pubmed/23247666", "http://www.ncbi.nlm.nih.gov/pubmed/17220471", "http://www.ncbi.nlm.nih.gov/pubmed/22879384", "http://www.ncbi.nlm.nih.gov/pubmed/22245792", "http://www.ncbi.nlm.nih.gov/pubmed/19675298", "http://www.ncbi.nlm.nih.gov/pubmed/23271797", "http://www.ncbi.nlm.nih.gov/pubmed/22709755", "http://www.ncbi.nlm.nih.gov/pubmed/22343711", "http://www.ncbi.nlm.nih.gov/pubmed/8735623", "http://www.ncbi.nlm.nih.gov/pubmed/16781216", "http://www.ncbi.nlm.nih.gov/pubmed/16775092", "http://www.ncbi.nlm.nih.gov/pubmed/20924097", "http://www.ncbi.nlm.nih.gov/pubmed/23596505" ], "ideal_answer": [ "Ranolazine has only a small effect on the basal calcium current, while it greatly affects whole cell calcium current when facilitated by beta-adrenoceptor or histamine receptor activation.\nRanolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload.\nRanolazine reduces Ca2+ overload and LV mechanical dysfunction during ischemia/reperfusion.\nranolazine decreases I(Na,L)-induced dysregulation of calcium cycling that contributes to the antiarrhythmic actions of this agent.\nranolazine desensitizes Ca(2+)-dependent RyR2 activation, and inhibits Ca(i) oscillations.\nranolazine ameliorates the Ca(2+) response and cross-bridge kinetics of cardiac myofilaments." ], "concepts": [ "http://www.uniprot.org/uniprot/CCAMK_ORYSJ", "http://www.uniprot.org/uniprot/CCAMK_LOTJA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002118", "http://www.disease-ontology.org/api/metadata/DOID:114", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.uniprot.org/uniprot/CCAMK_PEA", "http://www.biosemantics.org/jochem#4277675", "http://www.biosemantics.org/jochem#4268168", "http://www.biosemantics.org/jochem#4071295", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.biosemantics.org/jochem#4000018", "http://www.biosemantics.org/jochem#4260677", "http://www.biosemantics.org/jochem#4202863", "http://www.biosemantics.org/jochem#4202864", "http://www.uniprot.org/uniprot/CCAMK_LILLO" ], "type": "summary", "id": "517138d98ed59a060a000003", "snippets": [ { "offsetInBeginSection": 957, "offsetInEndSection": 1131, "text": "Ranolazine and lidocaine (10 \u03bcM) similarly reduced Ca2+i overload and improved left ventricle work recovery in whole-heart models of IR injury or exposure to ouabain (80 \u03bcM).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22879384", "endSection": "sections.0" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1245, "text": "Ranolazine (10 \u03bcM), but not lidocaine (10 \u03bcM), reduced RM NCX1.1-mediated Ca2+i overload in ventricular myocytes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22879384", "endSection": "sections.0" }, { "offsetInBeginSection": 389, "offsetInEndSection": 583, "text": "Blockade of the late inward sodium current, late I(Na), offers another target for the treatment of ischemia. Blockade of late I(Na) reduces the sodium and calcium overload that follows ischemia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23247666", "endSection": "sections.0" }, { "offsetInBeginSection": 728, "offsetInEndSection": 952, "text": "Ranolazine, a late I(Na) inhibitor, has been shown to provide both anti-anginal and anti-ischemic benefits without significant alterations in the heart rate and blood pressure in patients with stable coronary artery disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23247666", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 171, "text": "Ranolazine is a new antianginal drug that reduces intracellular sodium and calcium accumulation during ischemia, thus potentially limiting myocardial ischemia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22709755", "endSection": "sections.0" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1544, "text": "Detergent extracted fiber bundles from DOCA-salt hearts demonstrated increased myofilament response to Ca(2+) with glutathionylation of myosin binding protein C. Treatment with ranolazine ameliorated the Ca(2+) response and cross-bridge kinetics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343711", "endSection": "sections.0" }, { "offsetInBeginSection": 1770, "offsetInEndSection": 1875, "text": "Ran reduces P(o) of RyR2, desensitizes Ca(2+)-dependent RyR2 activation, and inhibits Ca(i) oscillations,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22245792", "endSection": "sections.0" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1748, "text": "Ranolazine may provide functional protection of the heart during IR injury by reducing cCa2+ and mCa2+ loading secondary to its effect to block the late Na+ current.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21741479", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 123, "text": "Ranolazine is a novel antianginal medication that acts by ameliorating disturbed sodium and calcium homeostasis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20924097", "endSection": "sections.0" }, { "offsetInBeginSection": 124, "offsetInEndSection": 248, "text": "By preventing myocyte sodium and calcium overload, ranolazine also have potential beneficial effects on myocardial function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20924097", "endSection": "sections.0" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1734, "text": "Reduction by RAN of I(Na,L)-induced dysregulation of calcium cycling could contribute to the antiarrhythmic actions of this agent in both reentrant and triggered arrhythmias.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19675298", "endSection": "sections.0" }, { "offsetInBeginSection": 1743, "offsetInEndSection": 2048, "text": "Moreover, in rabbit myocytes the increases in late I(Na), [Na(+)](i) and [Ca(2+)](i) caused by ATX-II, were significantly blunted by ranolazine. These results suggest that ranolazine may be of therapeutic benefit in conditions of diastolic dysfunction due to elevated [Na(+)](i) and diastolic [Ca(2+)](i).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18439620", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Ranolazine is a selective inhibitor of the late sodium current relative to peak sodium channel current, and via this mechanism, it may decrease sodium-dependent intracellular calcium overload during ischemia and reperfusion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17220471", "endSection": "sections.0" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1597, "text": "he beneficial effects of ranolazine in reducing Ca2+ overload and LV mechanical dysfunction during ischemia/reperfusion is consistent with the inhibition of late INa mechanism of action.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17027025", "endSection": "sections.0" }, { "offsetInBeginSection": 219, "offsetInEndSection": 338, "text": "Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16781216", "endSection": "sections.0" }, { "offsetInBeginSection": 1425, "offsetInEndSection": 1661, "text": "Ranolazine selectively inhibits late I(Na), reduces [Na(+)](i)-dependent calcium overload and attenuates the abnormalities of ventricular repolarisation and contractility that are associated with ischaemia/reperfusion and heart failure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16775092", "endSection": "sections.0" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1632, "text": "The results indicate that ranolazine, at concentrations which have significantly beneficial effects during ischaemic episodes, only greatly affects whole cell calcium current when facilitated by beta-adrenoceptor or histamine receptor activation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8735623", "endSection": "sections.0" }, { "offsetInBeginSection": 642, "offsetInEndSection": 705, "text": "Ranolazine had only a small effect on the basal calcium current", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8735623", "endSection": "sections.0" } ] }, { "body": "Which is the primary distinction between the Reverse Warburg effect and the conventional Warburg effect?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19923890", "http://www.ncbi.nlm.nih.gov/pubmed/22236875", "http://www.ncbi.nlm.nih.gov/pubmed/25197670", "http://www.ncbi.nlm.nih.gov/pubmed/20495363", "http://www.ncbi.nlm.nih.gov/pubmed/22313602", "http://www.ncbi.nlm.nih.gov/pubmed/21778829", "http://www.ncbi.nlm.nih.gov/pubmed/22395432", "http://www.ncbi.nlm.nih.gov/pubmed/21300172", "http://www.ncbi.nlm.nih.gov/pubmed/23388463", "http://www.ncbi.nlm.nih.gov/pubmed/20818174", "http://www.ncbi.nlm.nih.gov/pubmed/23844381", "http://www.ncbi.nlm.nih.gov/pubmed/21558814", "http://www.ncbi.nlm.nih.gov/pubmed/23443971", "http://www.ncbi.nlm.nih.gov/pubmed/21521946", "http://www.ncbi.nlm.nih.gov/pubmed/20562527" ], "ideal_answer": [ "The conventional \"Warburg effect\" reffers to the metabolic shift of cancer cells towards aerobic glycolysis, due to mitochondrial dysfunction. The \"reverse Warburg effect\" or \"parasitic\" energy-transfer, is a model of \"two-compartment tumor metabolism\". In this model, cancer cells secrete hydrogen peroxide (H2O2), initiating oxidative stress and aerobic glycolysis in the tumor stroma. The cancer-associated fibroblasts of the stroma are glycolytic and lack detectable mitochondria. These glycolytic stromal cells produce mitochondrial fuels (L-lactate, ketone bodies and chemical building blocks, such as amino acids -glutamine-, and nucleotides) that are then transferred to oxidative epithelial cancer cells. Lactate and ketones drive cancer cell oxidative mitochondrial metabolism (OXPHOS), and building blocks sustain the anabolic needs of rapidly proliferating cancer cells. Therefore, according to the \"reverse Warburg effect\", stromal catabolism fuels anabolic tumor growth via energy transfer. Thus, in \"reverse Warburg effect\" the cancer-associated fibroblasts of the stroma undergo aerobic glycolysis, rather than epithelial cancer cells themselves, as proposed by the conventional \"Warburg effect\"." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004129" ], "type": "summary", "id": "554403395beec11c10000001", "snippets": [ { "offsetInBeginSection": 717, "offsetInEndSection": 1017, "text": "The metabolic energy transduction pathways are strongly affected in cancers. Mitochondrial dysfunction in cancer cells (Warburg effect) or in fibroblasts associated with cancer cells (reverse Warburg effect) results in decreased or increased power of the generated electromagnetic field, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23844381", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1209, "text": "cigarette smoke induces catabolism in the local microenvironment, directly fueling oxidative mitochondrial metabolism (OXPHOS) in neighboring epithelial cancer cells, actively promoting anabolic tumor growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388463", "endSection": "abstract" }, { "offsetInBeginSection": 1736, "offsetInEndSection": 1962, "text": "our current findings are consistent with the idea that cigarette smoke induces the \"reverse Warburg effect,\" thereby fueling \"two-compartment tumor metabolism\" and oxidative mitochondrial metabolism in epithelial cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 537, "text": "We have recently proposed a new two-compartment model for understanding the Warburg effect in tumor metabolism. In this model, glycolytic stromal cells produce mitochondrial fuels (L-lactate and ketone bodies) that are then transferred to oxidative epithelial cancer cells, driving OXPHOS and mitochondrial metabolism. Thus, stromal catabolism fuels anabolic tumor growth via energy transfer. We have termed this new cancer paradigm the \"reverse Warburg effect,\" because stromal cells undergo aerobic glycolysis, rather than tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22395432", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1151, "text": "Consistent with the \"reverse Warburg effect,\" our results indicate that metastatic breast cancer cells amplify oxidative mitochondrial metabolism (OXPHOS) and that adjacent stromal cells are glycolytic and lack detectable mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22395432", "endSection": "abstract" }, { "offsetInBeginSection": 1738, "offsetInEndSection": 1903, "text": "\"glycolytic\" cancer cells were rarely observed, indicating that the conventional \"Warburg effect\" does not frequently occur in cancer-positive lymph node metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22395432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 718, "text": "We have recently proposed a new model of cancer metabolism to explain the role of aerobic glycolysis and L-lactate production in fueling tumor growth and metastasis. In this model, cancer cells secrete hydrogen peroxide (H2O2), initiating oxidative stress and aerobic glycolysis in the tumor stroma. This, in turn, drives L-lactate secretion from cancer-associated fibroblasts. Secreted L-lactate then fuels oxidative mitochondrial metabolism (OXPHOS) in epithelial cancer cells, by acting as a paracrine onco-metabolite. We have previously termed this type of two-compartment tumor metabolism the \"Reverse Warburg Effect,\" as aerobic glycolysis takes place in stromal fibroblasts, rather than epithelial cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22313602", "endSection": "abstract" }, { "offsetInBeginSection": 1850, "offsetInEndSection": 1909, "text": "the \"Reverse Warburg Effect\" or \"parasitic\" energy-transfer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22313602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 627, "text": "We have previously demonstrated that enhanced aerobic glycolysis and/or autophagy in the tumor stroma supports epithelial cancer cell growth and aggressive behavior, via the secretion of high-energy metabolites. These nutrients include lactate and ketones, as well as chemical building blocks, such as amino acids (glutamine) and nucleotides. Lactate and ketones serve as fuel for cancer cell oxidative metabolism, and building blocks sustain the anabolic needs of rapidly proliferating cancer cells. We have termed these novel concepts the \"Reverse Warburg Effect,\" and the \"Autophagic Tumor Stroma Model of Cancer Metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22236875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 667, "text": "Previously, we proposed that cancer cells behave as metabolic parasites, as they use targeted oxidative stress as a \"weapon\" to extract recycled nutrients from adjacent stromal cells. Oxidative stress in cancer-associated fibroblasts triggers autophagy and\u00a0 mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis, and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the \"reverse Warburg effect.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21778829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 450, "text": "Recently, we proposed a new mechanism for understanding the Warburg effect in cancer metabolism. In this new paradigm, cancer-associated fibroblasts undergo aerobic glycolysis, and extrude lactate to \"feed\" adjacent cancer cells, which then drives mitochondrial biogenesis and oxidative mitochondrial metabolism in cancer cells. Thus, there is vectorial transport of energy-rich substrates from the fibroblastic tumor stroma to anabolic cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21558814", "endSection": "abstract" }, { "offsetInBeginSection": 2073, "offsetInEndSection": 2487, "text": " the \"reverse Warburg effect,\" which states that cancer-associated fibroblasts undergo aerobic glycolysis, thereby producing lactate, which is utilized as a metabolic substrate by adjacent cancer cells. In this model, \"energy transfer\" or \"metabolic-coupling\" between the tumor stroma and epithelial cancer cells \"fuels\" tumor growth and metastasis, via oxidative mitochondrial metabolism in anabolic cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21558814", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 701, "text": "the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300172", "endSection": "abstract" }, { "offsetInBeginSection": 1367, "offsetInEndSection": 1637, "text": " stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm \"The Autophagic Tumor Stroma Model of Cancer Metabolism\", or the \"Reverse Warburg Effect\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300172", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1606, "text": "Our findings are consistent with the recently proposed \"Reverse Warburg Effect\" and the \"Autophagic Tumor Stroma Model of Cancer Metabolism.\" In these two complementary models, cancer cells induce oxidative stress in adjacent stromal cells, which then forces these stromal fibroblasts to undergo autophagy/mitophagy and aerobic glycolysis. This, in turn, produces recycled nutrients (lactate, ketones and glutamine) to feed anabolic cancer cells, which are undergoing oxidative mitochondrial metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21521946", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 418, "text": "cancer-associated fibroblasts undergo aerobic glycolysis and the resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP production via oxidative phosphorylation. We have termed this new paradigm \"The Reverse Warburg Effect.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20818174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Previously, we proposed a new model for understanding the Warburg effect in tumorigenesis and metastasis. In this model, the stromal fibroblasts would undergo aerobic glycolysis (a.k.a., the Warburg effect)--producing and secreting increased pyruvate/lactate that could then be used by adjacent epithelial cancer cells as \"fuel\" for the mitochondrial TCA cycle, oxidative phosphorylation, and ATP production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20562527", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 1228, "text": "In this alternative model of tumorigenesis, the epithelial cancer cells instruct the normal stroma to transform into a wound-healing stroma, providing the necessary energy-rich micro-environment for facilitating tumor growth and angiogenesis. In essence, the fibroblastic tumor stroma would directly feed the epithelial cancer cells, in a type of host-parasite relationship. We have termed this new idea the \"Reverse Warburg Effect.\" In this scenario, the epithelial tumor cells \"corrupt\" the normal stroma, turning it into a factory for the production of energy-rich metabolites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19923890", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1370, "text": "Warburg's original observation that tumors show a metabolic shift towards aerobic glycolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19923890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19923890", "endSection": "title" }, { "offsetInBeginSection": 389, "offsetInEndSection": 534, "text": "We have termed this new cancer paradigm the \"reverse Warburg effect,\" because stromal cells undergo aerobic glycolysis, rather than tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22395432", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1208, "text": "Thus, we conclude that ketones and lactate fuel tumor growth and metastasis, providing functional evidence to support the \"Reverse Warburg Effect\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20818174", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 536, "text": "We have termed this new cancer paradigm the \"reverse Warburg effect,\" because stromal cells undergo aerobic glycolysis, rather than tumor cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22395432", "endSection": "abstract" } ] }, { "body": "What is the role of per genes in circadian rhythm control?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16596306", "http://www.ncbi.nlm.nih.gov/pubmed/15817328" ], "ideal_answer": [ "PER1 and PER2 genes are involved in cell cycle regulation and tumor suppression, controlling expression of genes such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha." ], "concepts": [ "http://www.uniprot.org/uniprot/PER1_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032922", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002940", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042752", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007623" ], "type": "summary", "id": "53175e4fb166e2b806000008", "snippets": [ { "offsetInBeginSection": 787, "offsetInEndSection": 967, "text": "Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha is deregulated in mPer2 mutant mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 459, "text": "The Period (Per) genes are key circadian rhythm regulators in mammals. Expression of the mouse Per (mPer) genes have diurnal pattern in the suprachiamstic nuclei and in peripheral tissues. Genetic ablation mPER1 and mPER2 function results in a complete loss of circadian rhythm control based on wheel running activity in mice. In addition, these animals also display apparent premature aging and significant increase in neoplastic and hyperplastic phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 456, "text": "Period (Per) genes are key circadian rhythm regulators in mammals. Expression of mouse Per (mPer) genes has a diurnal pattern in the suprachiasmatic nucleus and in peripheral tissues. Genetic ablation mPER1 and mPER2 function results in a complete loss of circadian rhythm control based on wheel-running activity in mice. In addition, these animals also display apparent premature aging and a significant increase in neoplastic and hyperplastic phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15817328", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 967, "text": "The temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15817328", "endSection": "abstract" } ] }, { "body": "Can sorafenib activate AMPK?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23963659", "http://www.ncbi.nlm.nih.gov/pubmed/25080865", "http://www.ncbi.nlm.nih.gov/pubmed/25349646" ], "ideal_answer": [ "Sorafenib induces persisten AMPK activation" ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4243524", "http://www.biosemantics.org/jochem#4243524", "http://amigo.geneontology.org/amigo/term/GO:0031588" ], "type": "yesno", "id": "56c8318f5795f9a73e00000f", "snippets": [ { "offsetInBeginSection": 310, "offsetInEndSection": 452, "text": "Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25080865", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1271, "text": "Persistent activation of AMPK by sorafenib finally led to the impairment of glucose metabolism both in MCF-7 and SKBR3 cells as well as in the highly glycolytic MDA-MB-231 cells, resulting in cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23963659", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 450, "text": "Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25080865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25080865", "endSection": "title" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1396, "text": "Persistent activation of AMPK by sorafenib finally led to the impairment of glucose metabolism both in MCF-7 and SKBR3 cells as well as in the highly glycolytic MDA-MB-231 cells, resulting in cell death. This previously unrecognized long-term effect of sorafenib was mediated by AMPK-dependent inhibition of the mTORC1 pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23963659", "endSection": "abstract" } ] }, { "body": "What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16757427", "http://www.ncbi.nlm.nih.gov/pubmed/22037271", "http://www.ncbi.nlm.nih.gov/pubmed/22461032", "http://www.ncbi.nlm.nih.gov/pubmed/23090888", "http://www.ncbi.nlm.nih.gov/pubmed/21903771", "http://www.ncbi.nlm.nih.gov/pubmed/21279819", "http://www.ncbi.nlm.nih.gov/pubmed/22761178", "http://www.ncbi.nlm.nih.gov/pubmed/17379100", "http://www.ncbi.nlm.nih.gov/pubmed/11808344", "http://www.ncbi.nlm.nih.gov/pubmed/19641300", "http://www.ncbi.nlm.nih.gov/pubmed/14744784", "http://www.ncbi.nlm.nih.gov/pubmed/18205699", "http://www.ncbi.nlm.nih.gov/pubmed/14639002", "http://www.ncbi.nlm.nih.gov/pubmed/12755554", "http://www.ncbi.nlm.nih.gov/pubmed/12783369", "http://www.ncbi.nlm.nih.gov/pubmed/22160058", "http://www.ncbi.nlm.nih.gov/pubmed/16850123", "http://www.ncbi.nlm.nih.gov/pubmed/20425400", "http://www.ncbi.nlm.nih.gov/pubmed/22460758", "http://www.ncbi.nlm.nih.gov/pubmed/21672900", "http://www.ncbi.nlm.nih.gov/pubmed/11986206", "http://www.ncbi.nlm.nih.gov/pubmed/22895079", "http://www.ncbi.nlm.nih.gov/pubmed/12082821", "http://www.ncbi.nlm.nih.gov/pubmed/21892537", "http://www.ncbi.nlm.nih.gov/pubmed/20875546", "http://www.ncbi.nlm.nih.gov/pubmed/18974832", "http://www.ncbi.nlm.nih.gov/pubmed/23174189", "http://www.ncbi.nlm.nih.gov/pubmed/22087818", "http://www.ncbi.nlm.nih.gov/pubmed/22052279", "http://www.ncbi.nlm.nih.gov/pubmed/17382020", "http://www.ncbi.nlm.nih.gov/pubmed/12750692", "http://www.ncbi.nlm.nih.gov/pubmed/22191306", "http://www.ncbi.nlm.nih.gov/pubmed/23942795", "http://www.ncbi.nlm.nih.gov/pubmed/19075651", "http://www.ncbi.nlm.nih.gov/pubmed/23666688", "http://www.ncbi.nlm.nih.gov/pubmed/16146726", "http://www.ncbi.nlm.nih.gov/pubmed/17956348", "http://www.ncbi.nlm.nih.gov/pubmed/11870241", "http://www.ncbi.nlm.nih.gov/pubmed/17292736", "http://www.ncbi.nlm.nih.gov/pubmed/15739279", "http://www.ncbi.nlm.nih.gov/pubmed/12869662", "http://www.ncbi.nlm.nih.gov/pubmed/21672337", "http://www.ncbi.nlm.nih.gov/pubmed/16988930", "http://www.ncbi.nlm.nih.gov/pubmed/12411298", "http://www.ncbi.nlm.nih.gov/pubmed/23032801", "http://www.ncbi.nlm.nih.gov/pubmed/21203982", "http://www.ncbi.nlm.nih.gov/pubmed/23233201", "http://www.ncbi.nlm.nih.gov/pubmed/12173333", "http://www.ncbi.nlm.nih.gov/pubmed/17970609", "http://www.ncbi.nlm.nih.gov/pubmed/15899391", "http://www.ncbi.nlm.nih.gov/pubmed/15027317", "http://www.ncbi.nlm.nih.gov/pubmed/17364993", "http://www.ncbi.nlm.nih.gov/pubmed/21061842", "http://www.ncbi.nlm.nih.gov/pubmed/19064740", "http://www.ncbi.nlm.nih.gov/pubmed/12176881", "http://www.ncbi.nlm.nih.gov/pubmed/22519766", "http://www.ncbi.nlm.nih.gov/pubmed/20425355", "http://www.ncbi.nlm.nih.gov/pubmed/12796373", "http://www.ncbi.nlm.nih.gov/pubmed/22349810", "http://www.ncbi.nlm.nih.gov/pubmed/18533795", "http://www.ncbi.nlm.nih.gov/pubmed/17929114", "http://www.ncbi.nlm.nih.gov/pubmed/19254884", "http://www.ncbi.nlm.nih.gov/pubmed/17382013", "http://www.ncbi.nlm.nih.gov/pubmed/20945321", "http://www.ncbi.nlm.nih.gov/pubmed/17671641", "http://www.ncbi.nlm.nih.gov/pubmed/23285088", "http://www.ncbi.nlm.nih.gov/pubmed/16475128", "http://www.ncbi.nlm.nih.gov/pubmed/12200353", "http://www.ncbi.nlm.nih.gov/pubmed/15791812", "http://www.ncbi.nlm.nih.gov/pubmed/16689455", "http://www.ncbi.nlm.nih.gov/pubmed/22506320", "http://www.ncbi.nlm.nih.gov/pubmed/22985168", "http://www.ncbi.nlm.nih.gov/pubmed/22893108", "http://www.ncbi.nlm.nih.gov/pubmed/16843101", "http://www.ncbi.nlm.nih.gov/pubmed/19860186", "http://www.ncbi.nlm.nih.gov/pubmed/22151181", "http://www.ncbi.nlm.nih.gov/pubmed/20529808", "http://www.ncbi.nlm.nih.gov/pubmed/12454739", "http://www.ncbi.nlm.nih.gov/pubmed/20607973" ], "ideal_answer": [ "The fusion protein BCR-ABL" ], "exact_answer": [ "BCR-ABL" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010677", "http://www.biosemantics.org/jochem#4275840", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011505", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016044", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015464", "http://www.disease-ontology.org/api/metadata/DOID:8552" ], "type": "factoid", "id": "5324a8ac9b2d7acc7e000018", "snippets": [ { "offsetInBeginSection": 108, "offsetInEndSection": 193, "text": "CR-ABL-targeted TKI that inhibits BCR-ABL with greater potency compared with imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942795", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 135, "text": "reciprocal translocation between chromosomes 9 and 22 [t(9;22)(q34;q11), Philadelphia chromosome] creates a BCR-ABL1 fusion protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666688", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 780, "text": "A novel tyrosine kinase inhibitor (TKI), imatinib, has been confirmed as an effective targeted treatment in most CML patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666688", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 184, "text": "The availability of tyrosine kinase inhibitors (TKIs) has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23285088", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 492, "text": "The BCR/ABL fusion tyrosine kinase is expressed in chronic myeloid leukemia and Philadelphia-positive (Ph+) acute lymphoblastic leukemia cells, and its inhibition by the clinically used tyrosine kinase inhibitors imatinib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23233201", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 183, "text": "Chronic myeloid leukemia (CML) is a clonal malignant myeloproliferative disorder characterized by the expansion of hematopoietic cells carrying the Philadelphia chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23174189", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 556, "text": "Patients received imatinib after diagnosis and underwent regular laboratory monitoring (quantification of BCR-ABL ratio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23174189", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 494, "text": "CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090888", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 711, "text": "tyrosine kinase inhibitors (TKIs), imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090888", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 346, "text": "Characterized by a translocation between chromosomes 9 and 22, known as the Philadelphia chromosome, small-molecule tyrosine kinase inhibitors (TKIs) targeted against the oncogenic BCR-ABL fusion protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23032801", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 176, "text": "Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22985168", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 398, "text": "ABL-kinase inhibitors (AKIs) Imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22985168", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 120, "text": "hiladelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by constitutively activated BCR-ABL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22895079", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 324, "text": " BCR-ABL tyrosine kinase inhibitor imatinib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22895079", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 56, "text": "matinib was the first BCR-ABL tyrosine kinase inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893108", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 185, "text": "CML) is a pluripotent hematopoietic disorder that is currently considered incurable. The tyrosine kinase product of the Philadelphia chromosome, P210 BCR-ABL, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22761178", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 385, "text": "Imatinib mesylate, an orally available BCR-ABL kinase inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22761178", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 193, "text": "Since the initial approval of imatinib much has been learned about its resistance mechanisms, and efforts have continued to improve upon BCR-ABL tyrosine kinase inhibitor therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22519766", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 202, "text": "CML) originates from a hematopoietic stem cell carrying the Philadelphia (Ph) chromosome and oncogenic BCR-ABL1 fusion gene. The first tyrosine-kinase inhibitor (TKI) imatinib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22506320", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 171, "text": "chronic myeloid leukemia (CML) patients ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461032", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 455, "text": "Philadelphia chromosome and/or BCR-ABL positive, received first-line treatment with imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461032", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 152, "text": "matinib mesylate is the sole BCR-ABL tyrosine kinase inhibitor approved as first-line treatment of accelerated-phase (AP) chronic myeloid leukemia (CML", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22460758", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 64, "text": "Imatinib is an inhibitor of the Bcr-Abl tyrosine kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22349810", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 160, "text": "Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has revolutionized the treatment of Bcr-Abl positive chronic myeloid leukemia ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22191306", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 575, "text": "The development of first-generation (imatinib) and second-generation (dasatinib and nilotinib) tyrosine kinase inhibitors (TKIs) that target the BCR-ABL1 fusion protein produced by the Ph chromosome revolutionized the treatment of chronic myelogenous leukemia (CML).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22160058", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 219, "text": "The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22151181", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 137, "text": "chronic myeloid leukemia (CML), BCR-ABL-mediated oncogenic signaling can be successfully targeted with the BCRABL- inhibitors imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22087818", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 195, "text": "matinib mesylate (STI 571; Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) is an orally available tyrosine kinase inhibitor that targets a constitutively activated BCR-ABL tyrosine kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22052279", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 448, "text": "Philadelphia chromosome positive chronic myelogenous leukemia (CML) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22052279", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 263, "text": "CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22037271", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 357, "text": "BCR-ABL levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903771", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 125, "text": "Imatinib induces a durable response in most patients with Philadelphia chromosome-positive chronic myeloid leukemia,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903771", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 295, "text": "CML is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome or the BCR-ABL fusion oncogene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21892537", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 373, "text": "imatinib therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21892537", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1186, "text": "The discovery of targeted tyrosine kinase inhibition of BCR-ABL kinase dramatically changed the treatment of CML. Imatinib, the first TKI approved for treatment of patients with Philadelphia chromosome--positive CML", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21672900", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 299, "text": "CML) is a genetically associated malignancy of haematopoietic stem cells, characterized by a t(9;22) translocation that forms the Philadelphia chromosome and creates a novel fusion gene, BCR-ABL. Treatment with molecular-targeted therapy is usually initiated with imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21672337", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 603, "text": "imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was started but Ph-positive chromosomes remained", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279819", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 848, "text": "CML is induced by the BCR-ABL oncogene, whose gene product is a BCR-ABL tyrosine kinase. Currently, inhibition of BCR-ABL kinase activity by its kinase inhibitor such as imatinib mesylate (Gleevec)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21203982", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 518, "text": "The Bcr-Abl tyrosine kinase inhibitor imatinib represented a major advance over conventional CML therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17382013", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 352, "text": "Imatinib (Glivec, Gleevec), a specific small molecule inhibitor of Bcr-Abl, has become the standard drug therapy for CML,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17379100", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 416, "text": "Imatinib blocks proliferation and induces apoptosis of BCR-ABL-expression in CML", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17364993", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 429, "text": "CML is the presence of a balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11.2), which is known as the Philadelphia (Ph) chromosome. This translocation results in the formation of the bcr-abl fusion gene,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17292736", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1005, "text": "emergence of imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17292736", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 210, "text": "matinib mesylate, binding to the inactive conformation of Bcr-Abl tyrosine kinase and suppressing the Ph chromosome positive clone, has revolutionized the treatment of chronic myeloid leukaemia (CML) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16988930", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 312, "text": "Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML). The translocation forms a chimeric gene, bcr-abl, which generates BCR-ABL. This fusion protein constitutively activate ABL tyrosine kinase and causes CML. Imatinib mesylate is a selective tyrosine kinase inhibitor on ABL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16850123", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 244, "text": "CML) is characterized by the presence of a BCR-ABL fusion gene, which is the result of a reciprocal translocation between chromosomes 9 and 22, and is cytogenetically visible as a shortened chromosome 22 (Philadelphia)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16843101", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 595, "text": "imatinib mesylate was introduced into the treatment regimen for CML", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16843101", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 179, "text": "matinib was developed as the first molecularly targeted therapy to specifically inhibit the BCR-ABL kinase in Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16757427", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 218, "text": "hronic myelogenous leukemia is characterized by the Philadelphia-chromosome, a shortened chromosome 22 which is the result of a reciprocal translocation between chromosome 9 and 22. The fusion gene is called BCR-ABL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16689455", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 621, "text": "Imatinib mesylate (Glivec) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16689455", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 611, "text": " BCR-ABL transcripts in the peripheral blood of patients with CML who were treated with imatinib mesylate (Glivec, Novartis)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16475128", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 450, "text": "Imatinib was the first small molecule developed to inhibit BCR-ABL tyrosine kinase ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16146726", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 60, "text": "hronic myeloid leukemia cells contain a BCR-ABL oncoprotein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16146726", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 246, "text": "Imatinib mesylate, a tyrosine kinase inhibitor with specific activity against the breakpoint cluster region--Abelson murine leukemia (BCR-ABL) tyrosine kinase has been developed for treatment of chronic myelogenous leukemia (CML).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21061842", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 489, "text": "The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph), which results in the synthesis of the breakpoint cluster region-Abelson murine leukemia (BCR-ABL) fusion oncoprotein, a constitutively active tyrosine kinase. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) that is specific for BCR-ABL, was a major breakthrough in CML therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20945321", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1157, "text": "original TKI, imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875546", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 759, "text": "CML were the discovery of the Philadelphia chromosome in 1960, and of the (9;22) translocation in 1973. There followed definition of the breakpoint cluster region on chromosome 22 in 1984 and the demonstration of the BCR-ABL transcript in CM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875546", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 186, "text": "Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has proved to be most effective therapy of Philadelphia chromosome-positive chronic myelogenous leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20607973", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 415, "text": "The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph) that results in the synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase (TK). The introduction of imatinib, a TK inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20529808", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 439, "text": "CML has enabled the development of Abl-specific tyrosine kinase inhibitors, such as imatinib mesylate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20425400", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 150, "text": "CML) arises as a consequence of a chromosomal translocation giving rise to the Philadelphia chromosome and Bcr-Abl oncogene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20425400", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 133, "text": "CML) is a paradigm for neoplasias that are defined by a unique genetic aberration, the BCR-ABL1 fusion gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19860186", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 257, "text": "protein tyrosine kinase inhibitor, imatinib,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19860186", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 150, "text": "BCR-ABL fusion gene represents the hallmark of chronic myelogenous leukemia (CML) and is derived from a translocation between chromosome 9 and 22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19641300", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 406, "text": "CML patients with imatinib treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19641300", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 244, "text": "CML) is characterized by the presence of the Philadelphia chromosome (Ph), a genetic aberration that codes for bcrabl, which plays a key role in disease pathophysiology. The first oral inhibitor of Brc-Abl was imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19254884", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 328, "text": "CML) is characterized by the presence of the Philadelphia (Ph) chromosome, which results from a reciprocal translocation between the long arms of the chromosomes 9 and 22 t(9;22)(q34;q11). This translocation creates two new genes, BCR-ABL on the 22q- (Ph chromosome) and the reciprocal ABL-BCR on 9q-. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19075651", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 801, "text": "tyrosine kinase inhibitor (TKI), introduced into clinical practice in 1998, was imatinib mesylate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19075651", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 613, "text": "BCR-ABL tyrosine kinase is the critical pathogenetic event in CML and an ideal target for therapy. This was confirmed in clinical trials of imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19064740", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 290, "text": "CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974832", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 279, "text": "CML) is the first human malignancy for which the promise of targeted therapy has come true. CML is invariably associated with a specific genetic lesion--the t(9;22) chromosomal translocation. As a consequence of this translocation, a BCR-ABL fusion gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18533795", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 631, "text": "Imatinib mesylate, an orally available tyrosine kinase inhibitor that targets Bcr-Abl,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18533795", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 173, "text": "CR-ABL tyrosine kinase inhibitors, such as imatinib (Gleevec) are highly effective in treating human Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18205699", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 174, "text": "Chronic myeloid leukemia (CML) is a hematopoietic stem cell cancer driven by the BCR-ABL fusion protein that arises from the translocation of chromosomes 9 and 22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17970609", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1005, "text": "BCR-ABL inhibitors, such as imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17970609", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 577, "text": "TKIs (tyrosine kinase inhibitors), including IM (imatinib mesylate),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17956348", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 228, "text": "chronic myeloid leukaemia) is a myeloproliferative disease that originates in an HSC (haemopoietic stem cell) as a result of the t(9;22) translocation, giving rise to the Ph (Philadelphia chromosome) and bcr-abl oncoprotein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17956348", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 310, "text": "CML) was the first human malignant disease to be linked to a single, acquired genetic abnormality. Identification of the Bcr-Abl kinase fusion protein and its pivotal role in the pathogenesis of CML provided new opportunities to develop molecular-targeted therapies. Imatinib mesylate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17929114", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 297, "text": " identification of the Philadelphia chromosome in cells from individuals with chronic myelogenous leukemia (CML) led to the recognition that the BCR-ABL tyrosine kinase causes CML. This in turn led to the development of imatinib mesylate, a clinically successful inhibitor of the BCR-ABL kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671641", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 441, "text": "CML) was the first human malignancy to be associated with a single genetic abnormality, characterized by a reciprocal translocation involving chromosomes 9 and 22 (the Philadelphia chromosome). The fusion gene that results (BCR-ABL) produces a constitutively activated tyrosine kinase that exists in different isoforms depending on BCR break-points. Imatinib mesylate is a highly selective inhibitor of this kinase,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20425355", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 358, "text": "CML) is characterized by the presence of the Philadelphia chromosome, which is associated with a balanced translocation involving chromosomes 9 and 22 to produce a fusion gene (bcr-abl) that gives rise to a constitutively activated Abl tyrosine kinase. This kinase led to the discovery of several small-molecule inhibitors, imatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17382020", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 163, "text": "matinib mesylate was designed as an inhibitor targeting the BCR-ABL tyrosine kinase, the molecular counterpart of the Philadelphia translocation t(9;22)(q34;q11).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15899391", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 431, "text": "CML) is a clonal hematopoietic disorder caused by the reciprocal translocation between chromosome 9 and 22. As a result of this translocation, a novel fusion gene, BCR-ABL, is created on Philadelphia (Ph) chromosome, and the constitutive activity of the BCR-ABL protein tyrosine kinase plays a critical role in the disease pathogenesis. Imatinib mesylate, a selective BCR-ABL tyrosine kinase inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15791812", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 458, "text": "CML was the first human cancer demonstrated to be strongly associated to the presence of a recurrent chromosomal translocation (the t(9;22)(q34;q11) that creates the Philadelphia (Ph)-chromosome) and to a specific molecular defect, the formation of a hybrid BCR-ABL gene ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15739279", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 747, "text": "imatinib, (Glivec, Gleevec, Novartis), a potent tyrosine kinase inhibitor of the Bcr-Abl protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15739279", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 391, "text": "matinib mesylate is a new drug that can inhibit the tyrosine kinase activity of Bcr-Abl, the receptors for platelet-derived growth factor receptor(PDGF) and stem cell factor, or c-kit. Chronic myeloid leukemia (CML) is distinguished by the presence of a reciprocal translocation between chromosomes 9 and 22 that results in a shortened chromosome 22, termed the Philadelphia(Ph) chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15027317", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 51, "text": "IM) binds to the BCR-ABL protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14744784", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 224, "text": "Philadelphia chromosome found in leukemia cells of chronic myelogenous leukemia (CML) patients is produced by translocation between chromosomes 9 and 22, resulting in expression of a chimera protein of Bcr and Abl kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14639002", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 416, "text": "Abl kinase inhibitors were synthesized. STI571 (imatinib mesylate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14639002", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 167, "text": "CML) is characterized by the Philadelphia translocation that fuses BCR sequences from chromosome 22 upstream of the ABL gene on chromosome 9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12869662", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 380, "text": "Imatinib, an ATP-competitive selective inhibitor of Bcr-Abl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12869662", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 183, "text": "Imatinib mesylate is a tyrosine kinase inhibitor with high affinity for the BCR-ABL fusion protein expressed by the hematopoietic cells in chronic myelogenous leukemia (CML).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12796373", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 414, "text": "BCR/ABL, encodes an activated tyrosine kinase that can act alone to induce a CML-like syndrome ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783369", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 593, "text": "The kinase inhibitor imatinib mesylate (Gleevec)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783369", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 240, "text": "hiladelphia chromosome translocation (t(9;22)) results in the molecular juxtaposition of two genes, BCR and ABL, to form an aberrant BCR-ABL gene on chromosome 22. BCR-ABL is critical to the pathogenesis of chronic myelogenous leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12755554", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 661, "text": "imatinib mesylate (Gleevec,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12755554", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 180, "text": "matinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12750692", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 174, "text": "matinib mesylate (STI571, Glivec, Gleevec) is a powerful inhibitor of the tyrosine kinase activity of Bcr-Abl, the oncoprotein responsible for chronic myeloid leukemia (CML)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12454739", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 238, "text": "CML) is characterized by the presence of a Bcr-Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of Bcr-Abl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12411298", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 398, "text": "Imatinib is an orally administered, potent inhibitor of the Bcr-Abl tyrosine kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200353", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 328, "text": "Imatinib mesylate (STI571), a selective inhibitor of the Bcr-Abl tyrosine kinase, has significant activity in AP CML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12176881", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 320, "text": "Chronic myelogenous leukemia (CML) is characterized by a molecular aberration, a fusion BCR-ABL gene encoding for aberrant tyrosine kinase activity, which is crucial in the pathogenesis of CML. In vitro, inhibition of BCR-ABL protein tyrosine kinase activity by a tyrosine kinase inhibitor, Imatinib mesylate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12173333", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 497, "text": "CML) is characterised by the occurrence of the Philadelphia (Ph) chromosome (9/22 translocation) and the formation of a fusion protein--the BCR-ABL transcript with constitutive activation of the BCR-ABL tyrosine kinase and consequent changes in the intracellular signal transduction, which is responsible for the deregulated myeloid cell proliferation. STI571 (signal transduction inhibition number 571) is a potent and selective inhibitor of the BCR-ABL tyrosine kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12082821", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 356, "text": "Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11986206", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 209, "text": "Chronic myelogenous leukemia (CML) is caused by the BCR-ABL tyrosine kinase, the product of the Philadelphia chromosome. Imatinib mesylate, formerly STI571, is a selective inhibitor of this kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11870241", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 265, "text": "CML) is a clonal hematopoietic stem cell disorder characterized by Philadelphia chromosome and resultant production of the constitutively activated BCR-ABL tyrosine kinase. Imatinib (STI571), selective inhibitor of the ABL-tyrosine kinase,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11808344", "endSection": "abstract" } ] }, { "body": "When was empagliflozin FDA approved?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25712444" ], "ideal_answer": [ "Empagliflozin was approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM)." ], "exact_answer": [ "2014" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014486", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017277" ], "type": "factoid", "id": "571e172bbb137a4b0c000002", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 257, "text": "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" } ] }, { "body": "Which R/bioconductor package is used for integrative genomics visualizations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24903420" ], "ideal_answer": [ "Sushi.R is a flexible, quantitative and integrative genomic visualizations for publication-quality multi-panel figures using common genomic data formats including Browser Extensible Data (BED), bedGraph and Browser Extensible Data Paired-End (BEDPE). Sushi.R is open source and made publicly available through GitHub (https://github.com/dphansti/Sushi) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/Sushi.html)." ], "exact_answer": [ "Sushi.R" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ], "type": "factoid", "id": "56b330bb39c782df06000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Sushi.R: flexible, quantitative and integrative genomic visualizations for publication-quality multi-panel figures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24903420", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 785, "text": "Interpretation and communication of genomic data require flexible and quantitative tools to analyze and visualize diverse data types, and yet, a comprehensive tool to display all common genomic data types in publication quality figures does not exist to date. To address this shortcoming, we present Sushi.R, an R/Bioconductor package that allows flexible integration of genomic visualizations into highly customizable, publication-ready, multi-panel figures from common genomic data formats including Browser Extensible Data (BED), bedGraph and Browser Extensible Data Paired-End (BEDPE). Sushi.R is open source and made publicly available through GitHub (https://github.com/dphansti/Sushi) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/Sushi.html).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24903420", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 588, "text": "To address this shortcoming, we present Sushi.R, an R/Bioconductor package that allows flexible integration of genomic visualizations into highly customizable, publication-ready, multi-panel figures from common genomic data formats including Browser Extensible Data (BED), bedGraph and Browser Extensible Data Paired-End (BEDPE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24903420", "endSection": "abstract" } ] }, { "body": "List symptoms of congenital toxoplasmosis triad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19744303", "http://www.ncbi.nlm.nih.gov/pubmed/25547178", "http://www.ncbi.nlm.nih.gov/pubmed/2089735", "http://www.ncbi.nlm.nih.gov/pubmed/7193392" ], "ideal_answer": [ "Classic triad of toxoplasmosis include hydrocephalus, cerebral calcification and chorioretinitis." ], "exact_answer": [ [ "hydrocephalus" ], [ "cerebral calcification" ], [ "chorioretinitis" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014125", "http://www.disease-ontology.org/api/metadata/DOID:13336", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816" ], "type": "list", "id": "56be06cdef6e394741000004", "snippets": [ { "offsetInBeginSection": 844, "offsetInEndSection": 1011, "text": "Most patients had systemic manifestations, but only 25% of diagnosed patients exhibited the classic triad of hydrocephalus, cerebral calcification and chorioretinitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547178", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 491, "text": "The pathogenic potential of T. gondii was recognized in the 1920s and 1930s, in congenitally infected children presenting with the classic triad of symptoms, namely hydrocephalus, retinochoroiditis and encephalitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19744303", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 728, "text": "Intracranial calcifications within the classical triad were only found in two cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7193392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Congenital toxoplasmosis is characterized by the classical triads: hydrocephaly, chorioretinitis and intracerebral calcifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2089735", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1012, "text": "Most patients had systemic manifestations, but only 25% of diagnosed patients exhibited the classic triad of hydrocephalus, cerebral calcification and chorioretinitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547178", "endSection": "abstract" } ] }, { "body": "How many genes are imprinted in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22894909", "http://www.ncbi.nlm.nih.gov/pubmed/17955261", "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "http://www.ncbi.nlm.nih.gov/pubmed/24501229", "http://www.ncbi.nlm.nih.gov/pubmed/11932239", "http://www.ncbi.nlm.nih.gov/pubmed/15802919", "http://www.ncbi.nlm.nih.gov/pubmed/17653590" ], "ideal_answer": [ "Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. ", "Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive. To date, fewer than 100 imprinted genes have been identified in the human genome." ], "exact_answer": [ " fewer than 100" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894" ], "type": "factoid", "id": "57090c33cf1c325851000013", "snippets": [ { "offsetInBeginSection": 203, "offsetInEndSection": 331, "text": "Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24501229", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 984, "text": "By applying dsPIG to the mRNA-Seq data, we predicted 94 imprinted genes in 20 cerebellum samples and 57 imprinted genes in 9 diverse tissue samples with expected low false discovery rates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1434, "text": "Interestingly, we found that, among biallelically expressed genes, at least 18 genes expressed significantly more transcripts from one allele than the other among different individuals and tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 286, "text": "To date, however, fewer than 100 imprinted genes have been identified in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 379, "text": "Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894909", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 781, "text": " In this study we analyzed the imprinting of 22 genes in human, mouse, and cattle and found that in only 11 was imprinting conserved across the three species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653590", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 1260, "text": "However, 62 unique clones in the library were characterized, all of which were methylated and GC-rich, with a GC content>50%. Of these, 43 clones also showed a CpG(obs)/CpG(exp)>0.6, of which 30 were studied in detail. These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11932239", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1350, "text": "Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17955261", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 363, "text": "To date, however, fewer than 100 imprinted genes have been identified in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 383, "text": "The Imprinted Gene Catalogue now has more than 200 genes listed, and estimates based on mouse models suggest many more may exist in humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802919", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1484, "text": "Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted. With samples of mRNA from appropriate tissues and a collection of informative cSNPs, a genome-wide search using this methodology could expand the list of genes that undergo genomic imprinting in a tissue- or temporal-specific manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17955261", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1250, "text": "We confirmed that PEG10 is paternally expressed, identified one gene (ZNF331) with multiple lines of data indicating it is imprinted, and predicted several additional imprinting candidate genes. Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17955261", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1250, "text": "Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17955261", "endSection": "abstract" } ] }, { "body": "Is exome sequencing efficient for the detection of germline mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24102379", "http://www.ncbi.nlm.nih.gov/pubmed/23341325", "http://www.ncbi.nlm.nih.gov/pubmed/23832012", "http://www.ncbi.nlm.nih.gov/pubmed/22468815" ], "ideal_answer": [ "Exome sequencing is an efficient, sensitive, rapid and relatively cheap method for detection of germline mutations." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018095", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059472", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004252", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017421" ], "type": "yesno", "id": "5318b452b166e2b806000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24102379", "endSection": "title" }, { "offsetInBeginSection": 1711, "offsetInEndSection": 1812, "text": "Whole exome sequencing is sensitive, rapid and efficient for detection of PCC/PGL germline mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24102379", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 649, "text": "These results from deep sequencing demonstrate a higher mutational detection rate than reported with conventional sequencing methodology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23832012", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 743, "text": "We performed exome sequencing of germline DNA from members of the affected family. Exome-wide analysis identified a novel loss-of-function mutation in the BAP1 gene, previously suggested as a tumor suppressor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23341325", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 576, "text": "whole-exome sequencing has been widely applied in the identification of germline mutations underlying Mendelian disorders, somatic mutations in various cancers and de novo mutations in neurodevelopmental disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22468815", "endSection": "abstract" } ] }, { "body": "Which cellular processes are regulated by Nanog?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19544407", "http://www.ncbi.nlm.nih.gov/pubmed/20962578", "http://www.ncbi.nlm.nih.gov/pubmed/20581802", "http://www.ncbi.nlm.nih.gov/pubmed/20578184", "http://www.ncbi.nlm.nih.gov/pubmed/22421047", "http://www.ncbi.nlm.nih.gov/pubmed/19139263", "http://www.ncbi.nlm.nih.gov/pubmed/22493428", "http://www.ncbi.nlm.nih.gov/pubmed/22315219", "http://www.ncbi.nlm.nih.gov/pubmed/22378194", "http://www.ncbi.nlm.nih.gov/pubmed/19415763", "http://www.ncbi.nlm.nih.gov/pubmed/16518401", "http://www.ncbi.nlm.nih.gov/pubmed/14728807", "http://www.ncbi.nlm.nih.gov/pubmed/22934707" ], "ideal_answer": [ "The pluripotency sustaining factor Nanog, controls a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination. Elevated expression of Nanog has also been reported to result in clonal expansion of murine ESCs, but it also plays a role in tumor development. A positive regulator of cell proliferation, it is essential for G1 to S transition in human embryonic stem cells while it regulates primordial germ cell migration." ], "exact_answer": [ [ "cell proliferation" ], [ "pluripotency" ], [ "cell fate determination" ], [ "G1 to S transition" ], [ "germ cell migration" ], [ "tumour development" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0065007", "http://www.uniprot.org/uniprot/NANOG_MOUSE" ], "type": "list", "id": "515d1ff7298dcd4e51000009", "snippets": [ { "offsetInBeginSection": 487, "offsetInEndSection": 536, "text": "critical for the regulation of cancer stem cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22934707", "endSection": "sections.0" }, { "offsetInBeginSection": 1525, "offsetInEndSection": 1665, "text": "the effect of FAK and Nanog cross-regulation on cancer cell morphology, invasion, and growth that plays a significant role in carcinogenesis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22493428", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Nanog-like regulates endoderm formation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421047", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421047", "endSection": "sections.0" }, { "offsetInBeginSection": 241, "offsetInEndSection": 338, "text": "we identified a zebrafish Nanog ortholog and found that its\u00a0knockdown impaired endoderm formation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421047", "endSection": "sections.0" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1047, "text": "establishes a role for Nanog-like in regulating the formation of the extraembryonic tissue required for endoderm induction", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421047", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Nanog regulates molecules involved in stemness and cell cycle-signaling pathway for maintenance of pluripotency", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22378194", "endSection": "title" }, { "offsetInBeginSection": 44, "offsetInEndSection": 170, "text": "Nanog, a key transcription factor in the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22378194", "endSection": "sections.0" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1015, "text": "Nanog, a positive regulator of ESC proliferation and G1/S transition", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315219", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Nanog is a stem cell transcription factor required for self-renewal and for maintaining pluripotency", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20962578", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "NANOG regulates glioma stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581802", "endSection": "title" }, { "offsetInBeginSection": 519, "offsetInEndSection": 626, "text": "We find that NANOG modulates gliomasphere clonogenicity, CD133(+) stem cell cell behavior and proliferation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581802", "endSection": "sections.0" }, { "offsetInBeginSection": 789, "offsetInEndSection": 831, "text": "NANOG is essential for GBM tumourigenicity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581802", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Nanog regulates primordial germ cell migration", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20578184", "endSection": "title" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1334, "text": "Nanog mediates PGC migration by regulating Cxcr4b expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20578184", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Nanog regulates proliferation during early fish development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19544407", "endSection": "title" }, { "offsetInBeginSection": 693, "offsetInEndSection": 777, "text": "Nanog is necessary for S-phase transition and proliferation in the developing embryo", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19544407", "endSection": "sections.0" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1293, "text": "our results demonstrate that NANOG, a cell-fate regulatory molecule known to be important for ESC self-renewal, also plays a novel role in tumor development", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19415763", "endSection": "sections.0" }, { "offsetInBeginSection": 25, "offsetInEndSection": 86, "text": "the self-renewal gene NANOG regulates human tumor development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19415763", "endSection": "title" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1134, "text": "The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16518401", "endSection": "sections.0" }, { "offsetInBeginSection": 58, "offsetInEndSection": 98, "text": "the pluripotency sustaining factor nanog", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14728807", "endSection": "title" } ] }, { "body": "In which cells are A-type lamins expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24213377", "http://www.ncbi.nlm.nih.gov/pubmed/21842415", "http://www.ncbi.nlm.nih.gov/pubmed/9363444", "http://www.ncbi.nlm.nih.gov/pubmed/9274531", "http://www.ncbi.nlm.nih.gov/pubmed/20568006", "http://www.ncbi.nlm.nih.gov/pubmed/2404771", "http://www.ncbi.nlm.nih.gov/pubmed/2415378", "http://www.ncbi.nlm.nih.gov/pubmed/7781761", "http://www.ncbi.nlm.nih.gov/pubmed/16179429", "http://www.ncbi.nlm.nih.gov/pubmed/9410886", "http://www.ncbi.nlm.nih.gov/pubmed/8381765", "http://www.ncbi.nlm.nih.gov/pubmed/17203376", "http://www.ncbi.nlm.nih.gov/pubmed/1808207", "http://www.ncbi.nlm.nih.gov/pubmed/2209722", "http://www.ncbi.nlm.nih.gov/pubmed/9367621" ], "ideal_answer": [ "In the rat brain, lamin A and C are expressed in relatively equal amounts, while the expressions of lamin B1 and B2 vary depending on the cell type. Human cells with reduced expression of the major B-type lamin protein, lamin B1, were generated using RNA interference. In addition, horizontal cells and a subpopulation of retinal ganglion cells expressed lamin A and C, while photoreceptor cells expressed neither lamin A nor C, and all other retinal neurons expressed lamin C only. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6.", "Early embryonic cells and stem cells of mammals generally possess only lamin B while lamins A and C appear later during differentiation. Northern analysis and immunoblotting demonstrated that lamin A/C mRNA and protein were not detectable in some human cell lines whereas lamin B1 was always present. Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B." ], "exact_answer": [ "late differentiating primary cells" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034882", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034904", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ], "type": "factoid", "id": "56ed27202ac5ed145900000c", "snippets": [ { "offsetInBeginSection": 676, "offsetInEndSection": 845, "text": "Antibodies specific for mouse A/C lamins, human A/C lamins, or B lamins have been used to define the lamin complement as a function of time in culture and of cell type. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2209722", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1234, "text": "dramatic increase in lamin A/C-positive cells was observed in the first 3 days of culture with both accessory cells and macrophages expressing lamins A/C as soon as such cell types could be identified. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2209722", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 332, "text": "Early embryonic cells and stem cells of mammals generally possess only lamin B while lamins A and C appear later during differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2404771", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 334, "text": "Northern analysis and immunoblotting demonstrated that lamin A/C mRNA and protein were not detectable in some human cell lines whereas lamin B1 was always present", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9367621", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 345, "text": "In the rat brain, lamin A and C are expressed in relatively equal amounts, while the expressions of lamin B1 and B2 vary depending on the cell type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21842415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2209722", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 941, "text": "These results demonstrated that EC cells devoid of lamins A and C nevertheless possessed the appropriate mechanisms for the localization and mitotic redistribution of exogenous lamins A and C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2404771", "endSection": "abstract" }, { "offsetInBeginSection": 1687, "offsetInEndSection": 1861, "text": "Spermatogonia and seminoma cells, which follow a differentiation pathway along the spermatogenic lineage and show characteristics of germ cells, do not express A-type lamins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9274531", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 667, "text": "While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1808207", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 476, "text": "B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16179429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "The expression of A-type lamins coincides with cell differentiation and as A-type lamins specifically interact with chromatin, a role in the regulation of differential gene expression has been suggested for A-type lamins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9410886", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 660, "text": "In the literature it is conveyed that only B-type lamins are required in these early stages of development and that A-type lamins are not present or required until differentiation of specific cell types associated with specialized tissue is initiated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17203376", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 292, "text": "B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16179429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 577, "text": "The nuclear lamina is a meshwork of intermediate filaments adjacent to the inner nuclear membrane that in mammalian cells is predominantly composed of three proteins: lamin A, lamin B, and lamin C. Because lamin A and C (A-type lamins) expression has been shown to be lacking in several types of undifferentiated or rapidly proliferating cells, we investigated lamin expression in the human liver in conditions with hepatocellular regeneration (cirrhosis of various etiologies and macroregenerative nodules) and in hepatocellular carcinomas of various grades of differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8381765", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1513, "text": "Our results identify the absence of A-type lamin expression as a novel marker for undifferentiated ES cells and further support a role for nuclear lamins in cell maintenance and differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16179429", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 523, "text": "In an attempt to provide an additional meaning to lamin-genome contacts, a recent study characterized the association of gene promoters with A-type lamins in progenitor and differentiated cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24213377", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 450, "text": "Previous studies have shown that lamin A/C is not expressed during mouse development before day 9, nor in undifferentiated mouse embryonic carcinoma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16179429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Ectopic expression of an A-type lamin does not interfere with differentiation of lamin A-negative embryonal carcinoma cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1808207", "endSection": "title" }, { "offsetInBeginSection": 503, "offsetInEndSection": 617, "text": "Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1808207", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 617, "text": "While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines. Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1808207", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 450, "text": "B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state. Previous studies have shown that lamin A/C is not expressed during mouse development before day 9, nor in undifferentiated mouse embryonic carcinoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16179429", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 503, "text": "On the basis of biochemical properties and sequence criteria, vertebrate lamin proteins are classified as either A- or B-type. While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1808207", "endSection": "abstract" } ] }, { "body": "What is the definition of autophagy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24308968", "http://www.ncbi.nlm.nih.gov/pubmed/23159909", "http://www.ncbi.nlm.nih.gov/pubmed/20116986", "http://www.ncbi.nlm.nih.gov/pubmed/19323652", "http://www.ncbi.nlm.nih.gov/pubmed/20595626", "http://www.ncbi.nlm.nih.gov/pubmed/23774579", "http://www.ncbi.nlm.nih.gov/pubmed/20404488", "http://www.ncbi.nlm.nih.gov/pubmed/21778180", "http://www.ncbi.nlm.nih.gov/pubmed/23422284", "http://www.ncbi.nlm.nih.gov/pubmed/16271306" ], "ideal_answer": [ "There are several definitions of autophagy. Among them, autophagy can be defined as a non- apoptotic programmed cell death that consists on a catabolic trafficking pathway for bulk destruction and turnover of long-lived proteins and organelles via regulated lysosomal degradation." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343" ], "type": "summary", "id": "5341d15dc45e133714000018", "snippets": [ { "offsetInBeginSection": 494, "offsetInEndSection": 604, "text": "autophagy, a process in which de novo formed membrane enclosed vesicles engulf and consume cellular components", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24308968", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1112, "text": "As a general definition, autophagy encompasses a range of processes in which the cell degrades parts of itself within the lysosome (or the analogous organelle, the vacuole, in yeast and plants), followed by the release and reuse of the breakdown products", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23774579", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 202, "text": "definition of autophagy is the following: all processes in which intracellular material is degraded within the lysosome/vacuole and where the macromolecular constituents are recycled", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159909", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1023, "text": "Autophagic PCD in animals is defined as being accompanied by an increase in the number of autophagosomes, autolysosomes, and small lytic vacuoles produced by autolysosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21778180", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 182, "text": "utophagy is the endogenous, tightly regulated cellular \"housekeeping\" process responsible for the degradation of damaged and dysfunctional cellular organelles and protein aggregates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20595626", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 156, "text": "utophagy has been predominantly studied as a nonselective self-digestion process that recycles macromolecules and produces energy in response to starvation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20404488", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 85, "text": "utophagy is a ubiquitous eukaryotic cytoplasmic quality and quantity control pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20116986", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 153, "text": "utophagy is a catabolic trafficking pathway for bulk destruction and turnover of long-lived proteins and organelles via regulated lysosomal degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19323652", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 161, "text": " non-apoptotic programmed cell death, such as autophagy ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16271306", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 292, "text": "utophagy and senescence share a number of characteristics, which suggests that both responses could serve to collaterally protect the cell from the toxicity of external stress such as radiation and chemotherapy and internal forms of stress such as telomere shortening and oncogene activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422284", "endSection": "abstract" } ] }, { "body": "Gene silencing can be achieved by RNA interference (RNAi) in eukaryotic organisms. What is the name of the analogous process in prokaryotic organisms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20109154", "http://www.ncbi.nlm.nih.gov/pubmed/16545108", "http://www.ncbi.nlm.nih.gov/pubmed/19706170", "http://www.ncbi.nlm.nih.gov/pubmed/21441598", "http://www.ncbi.nlm.nih.gov/pubmed/17537822", "http://www.ncbi.nlm.nih.gov/pubmed/18971321", "http://www.ncbi.nlm.nih.gov/pubmed/23439366", "http://www.ncbi.nlm.nih.gov/pubmed/19945378" ], "ideal_answer": [ "Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium." ], "exact_answer": [ "CRISPR-Cas" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=1900370", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016246", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=1900368", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011387", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056890", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005057" ], "type": "factoid", "id": "5157539ed24251bc0500008a", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 304, "text": "he CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23439366", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19945378", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Compelling evidence indicates that the CRISPR-Cas system protects prokaryotes from viruses and other potential genome invaders.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19945378", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "RNA in defense: CRISPRs protect prokaryotes against mobile genetic elements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21441598", "endSection": "title" }, { "offsetInBeginSection": 588, "offsetInEndSection": 777, "text": "n this article, we discuss our current understanding of this fascinating adaptive and heritable defense system, and describe functional similarities and differences with RNAi in eukaryotes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21441598", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 503, "text": "Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20109154", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "In many prokaryotes, noncoding RNAs that arise from the clustered regularly interspaced short palindromic repeat (CRISPR) loci are now thought to mediate defense against viruses and other molecular invaders by an RNAi-like pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971321", "endSection": "sections.0" } ] }, { "body": "Between which types of DNA bases are mutational biases introduced due to directional mutation pressure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20838599", "http://www.ncbi.nlm.nih.gov/pubmed/3357886", "http://www.ncbi.nlm.nih.gov/pubmed/2326195", "http://www.ncbi.nlm.nih.gov/pubmed/7932780", "http://www.ncbi.nlm.nih.gov/pubmed/2253708", "http://www.ncbi.nlm.nih.gov/pubmed/1556753", "http://www.ncbi.nlm.nih.gov/pubmed/8411203", "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "http://www.ncbi.nlm.nih.gov/pubmed/3454289", "http://www.ncbi.nlm.nih.gov/pubmed/1978331", "http://www.ncbi.nlm.nih.gov/pubmed/8433382" ], "ideal_answer": [ "The rates of substitution mutations in two directions, v (from an AT-pair to a GC-pair) and u (from a GC-pair to an AT-pair), are usually not the same. Thereafter, the effect of mutation on a genome is not random but has a directionality toward higher or lower GC content of DNA. The net effect, v/(u + v), has previously been defined as directional mutation pressure. Thus, directional mutation pressure (GC/AT pressure) refers to mutational biases between alpha-bases (A or T) and gamma-bases (G or C)." ], "type": "summary", "id": "55424745ed966d112c000002", "snippets": [ { "offsetInBeginSection": 673, "offsetInEndSection": 820, "text": "directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 524, "text": "A/T-biased directional mutation pressure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8433382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "Rates of substitution mutations in two directions, v [from an A-T or T-A nucleotide pair (AT-pair) to a G-C or C-G nucleotide pair (GC-pair)] and u [from a GC-pair to an AT-pair], are usually not the same. The net effect, v/(u + v), has previously been defined as directional mutation pressure (mu D), which explains the wide interspecific variation and narrow intragenomic heterogeneity of DNA G + C content in bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1556753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The prokaryotic genetic code has been influenced by directional mutation pressure (GC/AT pressure) that has been exerted on the entire genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2253708", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 203, "text": "directional mutation pressure affecting the base composition of DNA, sometimes in the direction of increased GC content and at other times, in the direction of AT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1978331", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 234, "text": "GC content of DNA varies, as a result of directional mutation pressure (AT/GC pressure), especially in bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3454289", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 526, "text": "the effect of mutation on a genome is not random but has a directionality toward higher or lower guanine-plus-cytosine content of DNA, and this pressure generates directional changes more in neutral parts of the genome than in functionally significant parts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3357886", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 35, "text": "GC-biased mutation pressure", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2326195", "endSection": "title" }, { "offsetInBeginSection": 282, "offsetInEndSection": 586, "text": "Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8411203", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 973, "text": "The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 585, "text": "Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8411203", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 407, "text": "Directional mutation pressure, the heterogenicity in the likelihood of different nucleotide substitutions, is used to explain the increasing or decreasing guanine-cytosine content (GC%) in DNA and is represented by microD, in agreement with Sueoka (1962, Proc Natl Acad Sci USA 48:582-592).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7932780", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 420, "text": "The net effect, v/(u + v), has previously been defined as directional mutation pressure (mu D), which explains the wide interspecific variation and narrow intragenomic heterogeneity of DNA G + C content in bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1556753", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 975, "text": "The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 974, "text": "The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 585, "text": "Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8411203", "endSection": "abstract" } ] }, { "body": "Is it feasible to determine the complete proteome of yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23438854", "http://www.ncbi.nlm.nih.gov/pubmed/12912986", "http://www.ncbi.nlm.nih.gov/pubmed/23334424", "http://www.ncbi.nlm.nih.gov/pubmed/15768030", "http://www.ncbi.nlm.nih.gov/pubmed/14730684", "http://www.ncbi.nlm.nih.gov/pubmed/16784548" ], "ideal_answer": [ "Yes, since the complete genome of yeast is known." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015003" ], "type": "yesno", "id": "5157fce5d24251bc0500008c", "snippets": [ { "offsetInBeginSection": 101, "offsetInEndSection": 191, "text": "or model organisms like yeast, we can now quantify complete proteomes in just a few hours.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23438854", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334424", "endSection": "title" }, { "offsetInBeginSection": 488, "offsetInEndSection": 806, "text": "So far, attempts to generate such maps for any proteome have failed to reach complete proteome coverage. Here we use a strategy based on high-throughput peptide synthesis and mass spectrometry to generate an almost complete reference map (97% of the genome-predicted proteins) of the Saccharomyces cerevisiae proteome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334424", "endSection": "sections.0" } ] }, { "body": "Which mutations of alpha-myosin heavy chain gene are implicated in hypertrophic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11827928", "http://www.ncbi.nlm.nih.gov/pubmed/18480046", "http://www.ncbi.nlm.nih.gov/pubmed/8290568", "http://www.ncbi.nlm.nih.gov/pubmed/9884344", "http://www.ncbi.nlm.nih.gov/pubmed/8614836", "http://www.ncbi.nlm.nih.gov/pubmed/9869991", "http://www.ncbi.nlm.nih.gov/pubmed/15998695", "http://www.ncbi.nlm.nih.gov/pubmed/10066683", "http://www.ncbi.nlm.nih.gov/pubmed/9045856", "http://www.ncbi.nlm.nih.gov/pubmed/23986715", "http://www.ncbi.nlm.nih.gov/pubmed/18362229", "http://www.ncbi.nlm.nih.gov/pubmed/10231857", "http://www.ncbi.nlm.nih.gov/pubmed/18281382" ], "ideal_answer": [ "The following mutations of alpha-myosin heavy chain gene are implicated in hypertrophic cardiomyopathy: R403Q; Q1065H and Arg-249-->Gln" ], "exact_answer": [ [ "R403Q", "Arg403Gln" ], [ "Q1065H" ], [ "Arg-249-->Gln" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018995" ], "type": "list", "id": "530cf4e0c8a0b4a00c000004", "snippets": [ { "offsetInBeginSection": 209, "offsetInEndSection": 382, "text": "Accordingly, pressure overload by transverse aortic constriction (TAC) was induced in 2-month-old, male mice with and without a FHC (R403Q) mutation in \u03b1-myosin heavy chain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23986715", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 733, "text": "This model (designated TnI-203/MHC-403) was generated by crossbreeding mice with the Gly203Ser cardiac troponin I (TnI-203) and Arg403Gln alpha-myosin heavy chain (MHC-403) FHC-causing mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18362229", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Male but not female mice carrying a single R403Q missense allele for cardiac alpha-myosin heavy chain (M-alphaMHC(R403Q/+) and F-alphaMHC(R403Q/+), respectively) develop significant hypertrophic cardiomyopathy (HCM) compared with male and female wild-type mice (M-alphaMHC(+/+) and F-alphaMHC(+/+), respectively) after approximately 30 wk of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18281382", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 829, "text": "A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15998695", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 340, "text": "To understand further the pathogenesis of familial hypertrophic cardiomyopathy, we determined how the cardiomyopathy induced by an Arg403-->Gln missense mutation in the alpha-myosin heavy chain (403) is affected by chronically enhancing sympathetic drive by mating the mice with those overexpressing G(s)alpha (G(s)alpha x403). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11827928", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 410, "text": "A mouse model of FHC resulting from a mutation in the alpha-myosin heavy-chain (Arg403Gln) was used to study the electrophysiologic phenotype of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10231857", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 391, "text": "We used small-amplitude (0.25%) length-perturbation analysis to examine the mechanical properties of skinned left ventricular papillary muscle strips from mouse hearts bearing the R403Q mutation in the alpha-myosin heavy chain (alphaMHC403/+).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10066683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Genetically-manipulated mice harboring an alpha-myosin heavy chain Arg403Gln missense mutation (alpha-MHC403/+) display a phenotype characteristic of familial hypertrophic cardiomyopathy (FHC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9869991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "A new mouse cardiac electrophysiology method was used to study mice harboring an alpha-myosin heavy chain Arg403Gln missense mutation (alpha-MHC403/+), which results in histological and hemodynamic abnormalities characteristic of familial hypertrophic cardiomyopathy (FHC) and sudden death of uncertain etiology during exercise. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9045856", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 602, "text": "The introduction of the mouse model for FHC (the mouse expresses predominantly alpha-MHC as opposed to the beta-isoform in larger mammals) created a new paradigm for FHC based on finding enhanced motor function for R403Q alpha-MHC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18480046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "A mouse model of familial hypertrophic cardiomyopathy (FHC) was generated by the introduction of an Arg 403 --> Gln mutation into the alpha cardiac myosin heavy chain (MHC) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8614836", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1382, "text": "Biochemical analysis of one FHC mutant (Arg-249-->Gln) demonstrates that the structures formed by the mutant are solubilized at a lower ionic strength than those formed by wild-type MHC. We conclude that although the FHC mutant MHC is not labile, its assembly properties may be impaired.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8290568", "endSection": "abstract" } ] }, { "body": "Which are the cardiac manifestations of Marfan syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2225986", "http://www.ncbi.nlm.nih.gov/pubmed/15554020", "http://www.ncbi.nlm.nih.gov/pubmed/22457261", "http://www.ncbi.nlm.nih.gov/pubmed/11865681", "http://www.ncbi.nlm.nih.gov/pubmed/7113187", "http://www.ncbi.nlm.nih.gov/pubmed/20301510", "http://www.ncbi.nlm.nih.gov/pubmed/15755703", "http://www.ncbi.nlm.nih.gov/pubmed/24043612", "http://www.ncbi.nlm.nih.gov/pubmed/20232788", "http://www.ncbi.nlm.nih.gov/pubmed/16358146", "http://www.ncbi.nlm.nih.gov/pubmed/21161115", "http://www.ncbi.nlm.nih.gov/pubmed/8322324", "http://www.ncbi.nlm.nih.gov/pubmed/22397493", "http://www.ncbi.nlm.nih.gov/pubmed/9586150", "http://www.ncbi.nlm.nih.gov/pubmed/21866385", "http://www.ncbi.nlm.nih.gov/pubmed/9587454", "http://www.ncbi.nlm.nih.gov/pubmed/24030414", "http://www.ncbi.nlm.nih.gov/pubmed/11159287" ], "ideal_answer": [ "Cardiac manifestations of Marfan syndrome include aortic root dilation,aortic regurgitation, mitral valve prolapse and mitral valve regurgitation." ], "exact_answer": [ [ "aortic root dilation" ], [ "mitral valve prolapse" ], [ "aortic regurgitation" ], [ "mitral valve regurgitation" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382" ], "type": "list", "id": "530cf4e0c8a0b4a00c000005", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 115, "text": "Cardiac manifestations of Marfan syndrome include aortic root dilation and mitral valve prolapse (MVP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24030414", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 238, "text": "Marfan syndrome (MFS) is a genetic disorder of the connective tissue. Aortic root dilation is a main criterion of the Ghent Nosology. Dural ectasia and the presence of mitral valve prolapse (MVP) contribute to its systemic score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24043612", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 255, "text": "The typical cardiac manifestations of Marfan syndrome are aortic regurgitation with progressive dilatation of the aortic root, which may cause dissection and rupture of the ascending aorta, mitral valve prolapse and mitral valve regurgitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21161115", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 189, "text": "To describe the clinical cardiac manifestations and temporal evolution of Marfan syndrome in children; to estimate the incidence of annuloaortic ectasia and mitral valve prolapse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16358146", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 567, "text": "the presence of mitral valve prolapse, aortic root diameter, mitral and aortic valves regurgitation, and aortic enlargement during beta-blocker therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16358146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Cardiovascular manifestations in Marfan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11865681", "endSection": "title" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1149, "text": "The major cardiac diagnoses were aortic dilatation (1/3) and mitral valve prolapse with severe mitral regurgitation (2/3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11865681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Marfan syndrome is a hereditable disorder of connective tissue that causes several distinct cardiovascular abnormalities, including aortic regurgitation, dissection, and aneurysm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2225986", "endSection": "abstract" } ] }, { "body": "How is connected \"isolated Non-compaction cardiomyopathy\" with dilated cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "http://www.ncbi.nlm.nih.gov/pubmed/17947214" ], "ideal_answer": [ "Mutations in cardiac beta-myosin heavy chain and alpha-tropomyosin link isolated Non-compaction cardiomyopathy with dilated cardiomyopathy" ], "exact_answer": [ "via mutations in beta-MHC and alpha-TPM1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056830" ], "type": "factoid", "id": "530cf4e0c8a0b4a00c000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "A novel alpha-tropomyosin mutation associates with dilated and non-compaction cardiomyopathy and diminishes actin binding", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "endSection": "title" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1527, "text": "We show that a mutation in TPM1 is associated with DCM and a lethal, early onset form of NCCM, probably as a result of diminished actin binding caused by weakened charge-charge interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 931, "text": "We describe, in two separate autosomal-dominant NCCM families, the identification of mutations in the sarcomeric cardiac beta-myosin heavy chain gene (MYH7), known to be associated with hypertrophic cardiomyopathy (HCM), restricted cardiomyopathy (RCM), and dilated cardiomyopathy (DCM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17947214", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1133, "text": "These results confirm the genetic heterogeneity of NCCM and suggest that the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM with HCM, RCM, and DCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17947214", "endSection": "abstract" } ] }, { "body": "What is the role of AMPK in diabetic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23223177", "http://www.ncbi.nlm.nih.gov/pubmed/19561140", "http://www.ncbi.nlm.nih.gov/pubmed/22842069", "http://www.ncbi.nlm.nih.gov/pubmed/22146585", "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "http://www.ncbi.nlm.nih.gov/pubmed/21562078", "http://www.ncbi.nlm.nih.gov/pubmed/23380689", "http://www.ncbi.nlm.nih.gov/pubmed/21685727", "http://www.ncbi.nlm.nih.gov/pubmed/15367397" ], "ideal_answer": [ "AMPK activation protects cardiac structure and function by increasing cardiac autophagy in the diabetic heart. Decreased AMPK activity and the subsequent reduction in cardiac autophagy are central to the development of diabetic cardiomyopathy. In fact, dissociation of Bcl-2 from Beclin1 may be an important mechanism for preventing diabetic cardiomyopathy via AMPK activation that restores autophagy and protects against cardiac apoptosis. In addition, genetic inhibition of AMPK in cardiomyocytes attenuates cardiac autophagy, exacerbates cardiac dysfunction and increases mortality in diabetic mice. The modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy. Stimulation of AMPK by metformin or trimetazidine administration may represent a novel approach to treat diabetic cardiomyopathy." ], "concepts": [ "http://www.uniprot.org/uniprot/AAPK1_PONAB", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031588", "http://www.uniprot.org/uniprot/AAKG1_HUMAN", "http://www.uniprot.org/uniprot/AAKG2_HUMAN", "http://www.uniprot.org/uniprot/AAKB2_RAT", "http://www.uniprot.org/uniprot/AAPK2_RAT", "http://www.uniprot.org/uniprot/AAPK2_HUMAN", "http://www.uniprot.org/uniprot/AAPK1_CAEEL", "http://www.uniprot.org/uniprot/AAPK1_PIG", "http://www.uniprot.org/uniprot/AAPK2_PONAB", "http://www.uniprot.org/uniprot/AAKG1_BOVIN", "http://www.uniprot.org/uniprot/AAKB1_PIG", "http://www.uniprot.org/uniprot/AAPK1_MOUSE", "http://www.uniprot.org/uniprot/AAPK1_RAT", "http://www.uniprot.org/uniprot/AAKB1_BOVIN", "http://www.uniprot.org/uniprot/AAKG2_MOUSE", "http://www.uniprot.org/uniprot/AAKG1_RAT", "http://www.uniprot.org/uniprot/AAKB1_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004679", "http://www.uniprot.org/uniprot/AAKG1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:9351", "http://www.uniprot.org/uniprot/AAKG2_PONAB", "http://www.uniprot.org/uniprot/AAKB2_HUMAN", "http://www.uniprot.org/uniprot/AAKG1_PIG", "http://www.uniprot.org/uniprot/AAKB1_MOUSE", "http://www.uniprot.org/uniprot/AAKB1_PONAB", "http://www.uniprot.org/uniprot/AAPK2_MOUSE", "http://www.uniprot.org/uniprot/AAPK2_CAEEL", "http://www.uniprot.org/uniprot/AAPK1_HUMAN", "http://www.uniprot.org/uniprot/AAPK2_PIG", "http://www.uniprot.org/uniprot/AAKB2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.uniprot.org/uniprot/AAKB1_HUMAN", "http://www.uniprot.org/uniprot/AAKG_YEAST" ], "type": "summary", "id": "51753a948ed59a060a000029", "snippets": [ { "offsetInBeginSection": 269, "offsetInEndSection": 394, "text": "We recently reported that diabetes depresses AMP-activated protein kinase (AMPK) activity, inhibits MAPK8/JNK1-BCL2 signaling", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380689", "endSection": "sections.0" }, { "offsetInBeginSection": 539, "offsetInEndSection": 809, "text": "Activation of AMPK directly phosphorylates MAPK8, which mediates BCL2 phosphorylation and subsequent BECN1-BCL2 dissociation, leading to restoration of cardiac autophagy, protection against cardiac apoptosis, and ultimately improvement in cardiac structure and function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380689", "endSection": "sections.0" }, { "offsetInBeginSection": 325, "offsetInEndSection": 412, "text": "studies were shown that p38 MAPK stimulates glucose uptake through the AMPK activation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22146585", "endSection": "sections.0" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1725, "text": "Taken together, it is suggested that the modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22146585", "endSection": "sections.0" }, { "offsetInBeginSection": 698, "offsetInEndSection": 825, "text": "We conclude that AMPK activation protects cardiac structure and function by increasing cardiac autophagy in the diabetic heart.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685727", "endSection": "sections.0" }, { "offsetInBeginSection": 185, "offsetInEndSection": 333, "text": "Genetic inhibition of AMPK in cardiomyocytes attenuates cardiac autophagy, exacerbates cardiac dysfunction and increases mortality in diabetic mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685727", "endSection": "sections.0" }, { "offsetInBeginSection": 579, "offsetInEndSection": 803, "text": "Oxidative stress and lipid deposition were markedly increased in the myocardium, concomitant with inactivation of AMPK and increased expression of peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1 alpha).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "endSection": "sections.0" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1107, "text": "Trimetazidine also caused AMPK activation and reduced PGC-1 alpha expression in the hearts of db/db mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "endSection": "sections.0" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1377, "text": "The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1 alpha were involved in this process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "endSection": "sections.0" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1125, "text": "Our findings highlight a role of PP2C and AMPK in the derangements of cardiac lipid metabolism in obesity and provide new insights as to the mechanisms of the liporegulatory disorder leading to lipotoxic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15367397", "endSection": "sections.0" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1050, "text": "We conclude that dissociation of BCL2 from BECN1 through activation of MAPK8-BCL2 signaling may be an important mechanism by which AMPK activation restores autophagy, protects against cardiac apoptosis, and prevents diabetic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380689", "endSection": "sections.0" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1666, "text": "Both the AMPK activator resveratrol and the antioxidant N-acetylcysteine mimicked the UCF-101-induced beneficial effect in STZ-induced diabetic cardiomyocytes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561140", "endSection": "sections.0" }, { "offsetInBeginSection": 2038, "offsetInEndSection": 2156, "text": "UCF-101 protects against STZ-induced cardiomyocyte contractile dysfunction, possibly via an AMPK-associated mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561140", "endSection": "sections.0" } ] }, { "body": "Are circRNAs associated with diseases and traits?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "http://www.ncbi.nlm.nih.gov/pubmed/24339831" ], "ideal_answer": [ "Yes. Circular RNAs (circRNAs) play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194" ], "type": "yesno", "id": "56b73c7a345adcac48000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "endSection": "title" }, { "offsetInBeginSection": 258, "offsetInEndSection": 508, "text": "Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 806, "text": "Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1086, "text": "Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 808, "text": "In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 990, "text": "Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "endSection": "abstract" } ] }, { "body": "Which is the most common cause of sudden cardiac death in young athletes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15929462", "http://www.ncbi.nlm.nih.gov/pubmed/21858983", "http://www.ncbi.nlm.nih.gov/pubmed/11886323", "http://www.ncbi.nlm.nih.gov/pubmed/12793636", "http://www.ncbi.nlm.nih.gov/pubmed/12651044", "http://www.ncbi.nlm.nih.gov/pubmed/21234187", "http://www.ncbi.nlm.nih.gov/pubmed/6686529", "http://www.ncbi.nlm.nih.gov/pubmed/20962423", "http://www.ncbi.nlm.nih.gov/pubmed/7788945", "http://www.ncbi.nlm.nih.gov/pubmed/17157688", "http://www.ncbi.nlm.nih.gov/pubmed/18384577", "http://www.ncbi.nlm.nih.gov/pubmed/18325444", "http://www.ncbi.nlm.nih.gov/pubmed/19336382", "http://www.ncbi.nlm.nih.gov/pubmed/22846097", "http://www.ncbi.nlm.nih.gov/pubmed/16352133", "http://www.ncbi.nlm.nih.gov/pubmed/20378375", "http://www.ncbi.nlm.nih.gov/pubmed/20559995", "http://www.ncbi.nlm.nih.gov/pubmed/6446987", "http://www.ncbi.nlm.nih.gov/pubmed/1554567", "http://www.ncbi.nlm.nih.gov/pubmed/22874472", "http://www.ncbi.nlm.nih.gov/pubmed/8667563", "http://www.ncbi.nlm.nih.gov/pubmed/10798028", "http://www.ncbi.nlm.nih.gov/pubmed/21160605", "http://www.ncbi.nlm.nih.gov/pubmed/19575162", "http://www.ncbi.nlm.nih.gov/pubmed/9858396", "http://www.ncbi.nlm.nih.gov/pubmed/9636339", "http://www.ncbi.nlm.nih.gov/pubmed/17853713", "http://www.ncbi.nlm.nih.gov/pubmed/8198037", "http://www.ncbi.nlm.nih.gov/pubmed/17322504", "http://www.ncbi.nlm.nih.gov/pubmed/17961794", "http://www.ncbi.nlm.nih.gov/pubmed/21716109", "http://www.ncbi.nlm.nih.gov/pubmed/11043079", "http://www.ncbi.nlm.nih.gov/pubmed/1450882", "http://www.ncbi.nlm.nih.gov/pubmed/23681420" ], "ideal_answer": [ "the most common cause of sudden cardiac death in young athletes is hypertrophic cardiomyopathy" ], "exact_answer": [ "hypertrophic cardiomyopathy" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016757", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002423" ], "type": "factoid", "id": "530cf4e0c8a0b4a00c000006", "snippets": [ { "offsetInBeginSection": 1077, "offsetInEndSection": 1216, "text": "The most common cause of death was hypertrophic cardiomyopathy (30 %), followed by coronary artery anomalies (9 %), and myocarditis (9 %). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681420", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 319, "text": "The most common cause of this, hypertrophic cardiomyopathy (HCM), is a genetic disorder responsible for more than a third of cases and is manageable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22846097", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 881, "text": "HCM is the most common cause of sudden death in young competitive athletes and preparticipation screening programs have to be implemented to avoid these tragic fatalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21160605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in young people, including trained athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20962423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Hypertrophic cardiomyopathy (HCM) is regarded as the most common cause of sudden cardiac death in young people (including trained athletes). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20559995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people, including trained athletes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18384577", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Hypertrophic cardiomyopathy is regarded as the most common cause of sudden cardiac death in young people (including trained athletes).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378375", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 563, "text": "The most common cause of sudden cardiac death in athletes is hypertrophic cardiomyopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17853713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Hypertrophic cardiomyopathy (HCM) is one of the most common inherited primary cardiac disorders and the most common cause of sudden cardiac death in young athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17157688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The most common cause of sudden cardiac death in individuals aged less than 35 years, including competitive athletes, is the inherited disorder hypertrophic cardiomyopathy (HCM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16352133", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 261, "text": "udden death in young competitive athletes is due to a variety of cardiovascular diseases (CVDs) and, most commonly, HCM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12651044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Hypertrophic cardiomyopathy (HCM) is the most common cause of death in the young, particularly in young competitive athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7788945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Hypertrophic cardiomyopathy (HC) is probably the most common cause of sudden cardiac death in youthful athletes, and this diagnosis has represented a contraindication to continued participation in competitive sports. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8198037", "endSection": "abstract" } ] }, { "body": "Could the Menzerath-Altmann law be proved mathematically trivial in genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25503672" ], "ideal_answer": [ "Yes. The view of Menzerath-Altmann law in genomes, as inevitable, is seriously flawed." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ], "type": "yesno", "id": "56bb1b4eac7ad10019000004", "snippets": [ { "offsetInBeginSection": 581, "offsetInEndSection": 1101, "text": "Here we review the statistical foundations of that test and consider three non-parametric tests based upon different correlation metrics and one parametric test to evaluate if Z \u223c 1/X in genomes. The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z \u223c 1/X in nine out of 11 taxonomic groups and detect a borderline group. Rather than a fact, Z \u223c 1/X is a baseline that real genomes do not meet. The view of Menzerath-Altmann law as inevitable is seriously flawed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25503672", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1163, "text": "The view of Menzerath-Altmann law as inevitable is seriously flawed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25503672", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1101, "text": "The view of Menzerath-Altmann law as inevitable is seriously flawed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25503672", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1107, "text": "The view of Menzerath-Altmann law as inevitable is seriously flawed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25503672", "endSection": "abstract" } ] }, { "body": "What is the rate of survival after commotio cordis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23107651", "http://www.ncbi.nlm.nih.gov/pubmed/23015869", "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "http://www.ncbi.nlm.nih.gov/pubmed/11555799", "http://www.ncbi.nlm.nih.gov/pubmed/21763255", "http://www.ncbi.nlm.nih.gov/pubmed/20086611" ], "ideal_answer": [ "Survival rates for commotio cordis are low, even when resuscitation is performed. Survival rates vary between 10% and 28%." ], "exact_answer": [ "10-28%" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013534", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056104" ], "type": "factoid", "id": "530cf4e0c8a0b4a00c000007", "snippets": [ { "offsetInBeginSection": 592, "offsetInEndSection": 779, "text": "At their commotio cordis event, 216 study patients were 0.2-51 years old (mean age 15\u00b19 years); 95% were males. Death occurred in 156 individuals (72%), while the other 60 (28%) survived.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23107651", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 864, "text": "In the 2 groups, events were largely similar demographically, including frequency of survival (26% in U.S. vs 25%; P = .84),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21763255", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1508, "text": "Survival of commotio cordis has risen from 10% to 15% since 2001.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015869", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1622, "text": "Only 21 (16%) individuals survived their event, with particularly prompt cardiopulmonary resuscitation/defibrillation (most commonly reversing ventricular fibrillation) the only identifiable factor associated with a favorable outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 435, "text": "Survival rates for commotio cordis are low, even with prompt CPR and defibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11555799", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 536, "text": "Survival is low, even when resuscitation is performed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20086611", "endSection": "abstract" } ] }, { "body": "What is the oldest human sample analysed by paleontology proteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18720427", "http://www.ncbi.nlm.nih.gov/pubmed/22348088", "http://www.ncbi.nlm.nih.gov/pubmed/23739949", "http://www.ncbi.nlm.nih.gov/pubmed/22848450", "http://www.ncbi.nlm.nih.gov/pubmed/17918181" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0096938", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0030224", "o": "http://linkedlifedata.com/resource/umls/label/A0096938" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0030224", "o": "http://linkedlifedata.com/resource/umls/label/A1308492" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1308492", "o": "paleontology" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0030224", "o": "http://linkedlifedata.com/resource/umls/label/A0096937" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0096937", "o": "Paleontology" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0096938", "o": "D010163" } ], "ideal_answer": [ "The Tyrolean Iceman's brain is the oldest (5300 years old) human sample that has been studied by paleoproteomics." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010163", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "summary", "id": "530a34eb970c65fa6b000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Paleoproteomic study of the Iceman's brain tissue.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739949", "endSection": "title" }, { "offsetInBeginSection": 189, "offsetInEndSection": 347, "text": "We report the first use of shotgun proteomics to detect the protein expression profile of buccal swabs and cloth samples from two 500-year-old Andean mummies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22848450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Identification of ancient biological samples from the 1991-discovered and more than 5300-year-old Tyrolean mummy, also called iceman or Oetzi, is very difficult. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18720427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "To determine whether a 2,700-year-old tumor can be reliably diagnosed using microscopic and proteomic techniques ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17918181", "endSection": "abstract" } ] }, { "body": "What are the results of loss of the protein Lon1 in the plant Arabidopsis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19076295", "http://www.ncbi.nlm.nih.gov/pubmed/22968828", "http://www.ncbi.nlm.nih.gov/pubmed/22023720" ], "ideal_answer": [ "Loss of Lon1 in Arabidopsis changes the mitochondrial proteome leading to altered metabolite profiles and growth retardation. Additionaly, seedling establishment is also impaired." ], "exact_answer": [ [ "growth rate deficit in both roots and shoots" ], [ "lowered activity of specific mitochondrial enzymes associated with respiratory metabolism" ], [ "impaired seedling establishment" ] ], "concepts": [ "http://www.uniprot.org/uniprot/LON_AQUAE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017360", "http://www.uniprot.org/uniprot/LON_MYCAP", "http://www.uniprot.org/uniprot/LON_DESDA", "http://www.uniprot.org/uniprot/LON_BUCAP", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029681", "http://www.uniprot.org/uniprot/LON_RICFE", "http://www.uniprot.org/uniprot/LON_ORITI", "http://www.uniprot.org/uniprot/LON_CHLT3", "http://www.uniprot.org/uniprot/LON_GEOMG", "http://www.uniprot.org/uniprot/LON_ERWAM", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049070" ], "type": "list", "id": "52e0141498d023950500000e", "snippets": [ { "offsetInBeginSection": 95, "offsetInEndSection": 305, "text": "Knockout in Arabidopsis (Arabidopsis thaliana) leads to a significant growth rate deficit in both roots and shoots and lowered activity of specific mitochondrial enzymes associated with respiratory metabolism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968828", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1493, "text": "loss of Lon1 significantly modifies respiratory function and plant performance by small but broad alterations in the mitochondrial proteome gained by subtly changing steady-state protein assembly, stability, and damage of a range of components that debilitate an anaplerotic role for mitochondria in cellular carbon metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968828", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1245, "text": "the lack of Lon selective proteolysis leading to growth retardation and impaired seedling establishment can be attributed to defects in the oil reserve mobilization pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Loss of Lon1 in Arabidopsis changes the mitochondrial proteome leading to altered metabolite profiles and growth retardation without an accumulation of oxidative damage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968828", "endSection": "title" }, { "offsetInBeginSection": 195, "offsetInEndSection": 363, "text": " a genetic screen was performed that led to the identification of Arabidopsis thaliana Lon1 protease mutants that exhibit a post-embryonic growth retardation phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19076295", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1267, "text": "mitochondria isolated from lon1 mutants had a lower capacity for respiration of succinate and cytochrome c via complexes II and IV, respectively. Furthermore, the activity of key enzymes of the tricarboxylic acid (TCA) cycle was significantly reduced. Additionally, mitochondria in lon1 mutants had an aberrant morphology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19076295", "endSection": "abstract" }, { "offsetInBeginSection": 1402, "offsetInEndSection": 1470, "text": " AtLon1 protease in organelle biogenesis and seedling establishment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19076295", "endSection": "abstract" } ] }, { "body": "Which gene is involved in Giant Axonal Neuropathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23248352", "http://www.ncbi.nlm.nih.gov/pubmed/25003002", "http://www.ncbi.nlm.nih.gov/pubmed/11971098", "http://www.ncbi.nlm.nih.gov/pubmed/19398414", "http://www.ncbi.nlm.nih.gov/pubmed/12398836", "http://www.ncbi.nlm.nih.gov/pubmed/24947478", "http://www.ncbi.nlm.nih.gov/pubmed/17587580", "http://www.ncbi.nlm.nih.gov/pubmed/23890932", "http://www.ncbi.nlm.nih.gov/pubmed/23332420", "http://www.ncbi.nlm.nih.gov/pubmed/24758703", "http://www.ncbi.nlm.nih.gov/pubmed/23316953", "http://www.ncbi.nlm.nih.gov/pubmed/25398950", "http://www.ncbi.nlm.nih.gov/pubmed/20949505", "http://www.ncbi.nlm.nih.gov/pubmed/19295179", "http://www.ncbi.nlm.nih.gov/pubmed/24211141", "http://www.ncbi.nlm.nih.gov/pubmed/24273072" ], "ideal_answer": [ "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin", "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene, resulting in a loss of a ubiquitously expressed protein, gigaxonin." ], "exact_answer": [ "GAN gene" ], "type": "factoid", "id": "572096c90fd6f91b6800000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398950", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 464, "text": "We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding of compound heterozygous mutations involving the GAN gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by autosomal recessive mutations in the GAN gene on chromosome 16q24.1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890932", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 136, "text": "Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Giant axonal neuropathy (GAN) is a rare pediatric neurodegenerative disease. It is best known for the \"giant\" axons caused by accumulations of intermediate filaments. The disease is progressive, with onset around age 3 years and death by the third decade of life. GAN results from recessive mutations in the GAN gene encoding gigaxonin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24947478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316953", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332420", "endSection": "title" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1027, "text": "In this family, missense mutation of c.224 T>A and missense mutation of c.1634G>A in GAN gene caused the phenotype of giant axonal neuropathy in the proband.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19295179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Different missense, nonsense and frameshift mutations in the GAN gene encoding gigaxonin have been described to cause giant axonal neuropathy, a severe early-onset progressive neurological disease with autosomal recessive inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949505", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1326, "text": "The giant axonal neuropathy gene was localised by homozygosity mapping to chromosome 16q24.1 and identified as encoding a novel, ubiquitously expressed cytoskeletal protein named gigaxonin.We describe a consanguineous Algerian family with three affected sibs aged 16, 14 and 12 years who present a mild demyelinating sensory motor neuropathy, hypoacousia and kyphoscoliosis which was moderate in the two elder patients, severe in the third one, with no sign of central nervous system involvement and normal cerebral magnetic resonance imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12398836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11971098", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248352", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248352", "endSection": "title" }, { "offsetInBeginSection": 224, "offsetInEndSection": 595, "text": "We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding of compound heterozygous mutations involving the GAN gene, including a novel interstitial microdeletion at 16q23.2 detected by microarray and a point mutation detected by direct sequencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211141", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 317, "text": "Indeed, recessive mutations in the Gigaxonin-encoding gene cause Giant Axonal Neuropathy (GAN), a severe neurodegenerative disorder characterized by a wide disorganization of the Intermediate Filament network", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24758703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316953", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "Giant axonal neuropathy (GAN)(1) is a rare autosomal recessive neurological disorder caused by mutations in the GAN gene that encodes gigaxonin, a member of the BTB/Kelch family of E3 ligase adaptor proteins.(1) This disease is characterized by the aggregation of Intermediate Filaments (IF)-cytoskeletal elements that play important roles in cell physiology including the regulation of cell shape, motility, mechanics and intra-cellular signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by autosomal recessive mutations in the GAN gene on chromosome 16q24.1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890932", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 331, "text": "Indeed, recessive mutations in the Gigaxonin-encoding gene cause Giant Axonal Neuropathy (GAN), a severe neurodegenerative disorder characterized by a wide disorganization of the Intermediate Filament network. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24758703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The instability of the BTB-KELCH protein Gigaxonin causes Giant Axonal Neuropathy and constitutes a new penetrant and specific diagnostic test.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24758703", "endSection": "title" }, { "offsetInBeginSection": 224, "offsetInEndSection": 596, "text": "We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding of compound heterozygous mutations involving the GAN gene, including a novel interstitial microdeletion at 16q23.2 detected by microarray and a point mutation detected by direct sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "INTRODUCTION: Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273072", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1130, "text": "Analysis of the microarray data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation of this gene has been linked to the development of giant axonal neuropathy (GAN), a rare autosomal recessive condition characterized by a progressive sensorimotor neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 392, "text": " Giant axonal neuropathy (GAN, MIM: 256850) is a devastating autosomal recessive disorder characterized by an early onset severe peripheral neuropathy, varying central nervous system involvement and strikingly frizzly hair. Giant axonal neuropathy is usually caused by mutations in the gigaxonin gene (GAN) but genetic heterogeneity has been demonstrated for a milder variant of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17587580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248352", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by autosomal recessive mutations in the GAN gene on chromosome 16q24.1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316953", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273072", "endSection": "abstract" } ] }, { "body": "Are there studies representing the involvement of Notch mutations in neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and cadasil syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17981814", "http://www.ncbi.nlm.nih.gov/pubmed/24101600", "http://www.ncbi.nlm.nih.gov/pubmed/21772710", "http://www.ncbi.nlm.nih.gov/pubmed/24252593", "http://www.ncbi.nlm.nih.gov/pubmed/24249312", "http://www.ncbi.nlm.nih.gov/pubmed/15640354", "http://www.ncbi.nlm.nih.gov/pubmed/19383720", "http://www.ncbi.nlm.nih.gov/pubmed/16126912", "http://www.ncbi.nlm.nih.gov/pubmed/19419698", "http://www.ncbi.nlm.nih.gov/pubmed/24191040", "http://www.ncbi.nlm.nih.gov/pubmed/23432468", "http://www.ncbi.nlm.nih.gov/pubmed/24244188", "http://www.ncbi.nlm.nih.gov/pubmed/24107444", "http://www.ncbi.nlm.nih.gov/pubmed/24140581", "http://www.ncbi.nlm.nih.gov/pubmed/11244211", "http://www.ncbi.nlm.nih.gov/pubmed/16473372", "http://www.ncbi.nlm.nih.gov/pubmed/24159576", "http://www.ncbi.nlm.nih.gov/pubmed/20205843" ], "ideal_answer": [ "The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in organisms as diverse as insects, nematodes, echinoderms and mammals. Disruptions in conserved developmental pathways frequently result in inherited congenital anomalies in humans. Mutations in genes encoding Notch pathway components underlie human disease such as Down syndrome, Pick's and Prion's disease, and cadasil syndrome." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051880", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059645" ], "type": "yesno", "id": "532bf822d6d3ac6a34000016", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 602, "text": "he Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252593", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 791, "text": "In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244188", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 327, "text": "Signaling pathways have become a major source of targets for novel therapies in hepatocellular carcinoma (HCC). Survival benefits achieved with sorafenib, a multikinase inhibitor, are unprecedented and underscore the importance of improving our understanding of how signaling networks interact in transformed cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24159576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16473372", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 401, "text": "(PSEN1) is the major locus for mutations causing familial Alzheimer's disease (FAD) and is also mutated in Pick disease of brain, familial acne inversa and dilated cardiomyopathy. It is a critical facilitator of Notch signalling and many other signalling pathways and protein cleavage events including production of the Amyloid\u03b2 (A\u03b2) peptide from the AMYLOID BETA A4 PRECURSOR PROTEIN (APP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101600", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 666, "text": "As beta-APP and Notch are both processed by gamma-secretase, we analyzed expression of the Notch signaling pathway in the adult DS brain and in a model system for DS, human trisomy 21 fibroblasts by quantitative PCR. In adult DS cortex we found that Notch1, Dll1 and Hes1 expression is up-regulated. Moreover, DS fibroblasts and Alzheimer disease cortex also show overexpression of Notch1 and Dll1, indicating that enhanced beta-APP processing found in both DS and AD could be instrumental in these changes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19419698", "endSection": "title" }, { "offsetInBeginSection": 4, "offsetInEndSection": 169, "text": "Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11244211", "endSection": "abstract" } ] }, { "body": "Are there any functional differences between Mfd and its human Cocaine syndrome protein B (CSB) homolog?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "http://www.ncbi.nlm.nih.gov/pubmed/8999876" ], "ideal_answer": [ "Both Cockayne syndrome protein B (CSB) and Mfd are involved in transcription-coupled repair. CSB is the human TCR coupling factor and Mfd is the bacterial TCR coupling factor. However, unlike Mfd, CSB does not act as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. Moreover, Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050783", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050784" ], "type": "yesno", "id": "553f8bc11d53b76422000002", "snippets": [ { "offsetInBeginSection": 214, "offsetInEndSection": 534, "text": "In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "endSection": "abstract" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1584, "text": "Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 813, "text": "CSB has an ATPase activity that is stimulated strongly by DNA; however, it neither acts as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8999876", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1572, "text": "In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1584, "text": "In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1086, "text": "In contrast, no difference was detected in the rate of transcription recovery in mfd, uvrA, fpg, nth, or polB dinB umuDC mutants relative to wild-type cells following oxidative damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "endSection": "abstract" } ] }, { "body": "What is membrane scission?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25429432", "http://www.ncbi.nlm.nih.gov/pubmed/24440309", "http://www.ncbi.nlm.nih.gov/pubmed/25783003", "http://www.ncbi.nlm.nih.gov/pubmed/25784211", "http://www.ncbi.nlm.nih.gov/pubmed/24102355", "http://www.ncbi.nlm.nih.gov/pubmed/24878737", "http://www.ncbi.nlm.nih.gov/pubmed/24753582", "http://www.ncbi.nlm.nih.gov/pubmed/24099087", "http://www.ncbi.nlm.nih.gov/pubmed/23252497", "http://www.ncbi.nlm.nih.gov/pubmed/24016602", "http://www.ncbi.nlm.nih.gov/pubmed/25232009", "http://www.ncbi.nlm.nih.gov/pubmed/25353823", "http://www.ncbi.nlm.nih.gov/pubmed/25202029", "http://www.ncbi.nlm.nih.gov/pubmed/23297414", "http://www.ncbi.nlm.nih.gov/pubmed/25664996" ], "ideal_answer": [ "Membrane scission is the final step in order to complete the budding process, pinching off of the vesicle. To promote membrane scission, dynamin proteins polymerize, wrap around, and constrict the membrane. The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers." ], "type": "summary", "id": "570a7594cf1c325851000026", "snippets": [ { "offsetInBeginSection": 161, "offsetInEndSection": 341, "text": "To promote membrane scission, dynamin proteins polymerize, wrap around, and constrict the membrane; however, the mechanism underlying their role in membrane fusion remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25784211", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 463, "text": " Its role in endocytosis may be mediated by its reported interaction with dynamin 2, a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25783003", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 340, "text": "Because the neck's radius is, in general, finite, membrane scission and the consequent pinching off of the vesicle can only occur if it is narrowed to permit the necessary membrane topological reformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353823", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25232009", "endSection": "title" }, { "offsetInBeginSection": 147, "offsetInEndSection": 277, "text": "ESCRT-III is the final complex in the pathway that assembles on endosomes and executes membrane scission of intraluminal vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24440309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25202029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Dynamin-2 is a pleiotropic GTPase whose best-known function is related to membrane scission during vesicle budding from the plasma or Golgi membranes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24102355", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 310, "text": " Force produced by actin similarly contributes in membrane scission in endocytosis or Golgi remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25664996", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 154, "text": "Dynamin 2 (Dyn2) is a ~100kDa GTPase that assembles around the necks of nascent endocytic and Golgi vesicles and catalyzes membrane scission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24016602", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 833, "text": "membrane scission protein dynamin-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24753582", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 657, "text": " Finally, a membrane scission event must occur to release the free virion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23252497", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 888, "text": " Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23297414", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 275, "text": "few can mediate membrane scission to complete the budding process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24099087", "endSection": "abstract" } ] }, { "body": "How many TAp73 isoforms have been identified in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21946516", "http://www.ncbi.nlm.nih.gov/pubmed/22457351", "http://www.ncbi.nlm.nih.gov/pubmed/19139399", "http://www.ncbi.nlm.nih.gov/pubmed/23159862", "http://www.ncbi.nlm.nih.gov/pubmed/23271007", "http://www.ncbi.nlm.nih.gov/pubmed/21807636", "http://www.ncbi.nlm.nih.gov/pubmed/19885566", "http://www.ncbi.nlm.nih.gov/pubmed/20615966", "http://www.ncbi.nlm.nih.gov/pubmed/20926182", "http://www.ncbi.nlm.nih.gov/pubmed/22388545", "http://www.ncbi.nlm.nih.gov/pubmed/16254107", "http://www.ncbi.nlm.nih.gov/pubmed/18342333", "http://www.ncbi.nlm.nih.gov/pubmed/15059898", "http://www.ncbi.nlm.nih.gov/pubmed/12235210", "http://www.ncbi.nlm.nih.gov/pubmed/20298673", "http://www.ncbi.nlm.nih.gov/pubmed/23470527", "http://www.ncbi.nlm.nih.gov/pubmed/11753569", "http://www.ncbi.nlm.nih.gov/pubmed/15610529", "http://www.ncbi.nlm.nih.gov/pubmed/14634023", "http://www.ncbi.nlm.nih.gov/pubmed/19861456", "http://www.ncbi.nlm.nih.gov/pubmed/12897129", "http://www.ncbi.nlm.nih.gov/pubmed/15975558", "http://www.ncbi.nlm.nih.gov/pubmed/12920125", "http://www.ncbi.nlm.nih.gov/pubmed/14676279", "http://www.ncbi.nlm.nih.gov/pubmed/15781249", "http://www.ncbi.nlm.nih.gov/pubmed/21852228", "http://www.ncbi.nlm.nih.gov/pubmed/16467208", "http://www.ncbi.nlm.nih.gov/pubmed/16322298", "http://www.ncbi.nlm.nih.gov/pubmed/19777343", "http://www.ncbi.nlm.nih.gov/pubmed/18546269", "http://www.ncbi.nlm.nih.gov/pubmed/15138575", "http://www.ncbi.nlm.nih.gov/pubmed/11830511", "http://www.ncbi.nlm.nih.gov/pubmed/16773194", "http://www.ncbi.nlm.nih.gov/pubmed/12944917", "http://www.ncbi.nlm.nih.gov/pubmed/18350258", "http://www.ncbi.nlm.nih.gov/pubmed/15803372", "http://www.ncbi.nlm.nih.gov/pubmed/17626635", "http://www.ncbi.nlm.nih.gov/pubmed/22056305", "http://www.ncbi.nlm.nih.gov/pubmed/20146801", "http://www.ncbi.nlm.nih.gov/pubmed/19148480", "http://www.ncbi.nlm.nih.gov/pubmed/18477895", "http://www.ncbi.nlm.nih.gov/pubmed/19509292", "http://www.ncbi.nlm.nih.gov/pubmed/20733477", "http://www.ncbi.nlm.nih.gov/pubmed/20803057", "http://www.ncbi.nlm.nih.gov/pubmed/16964385", "http://www.ncbi.nlm.nih.gov/pubmed/20842728", "http://www.ncbi.nlm.nih.gov/pubmed/20581467", "http://www.ncbi.nlm.nih.gov/pubmed/19615968", "http://www.ncbi.nlm.nih.gov/pubmed/21643019", "http://www.ncbi.nlm.nih.gov/pubmed/16083956", "http://www.ncbi.nlm.nih.gov/pubmed/17076661", "http://www.ncbi.nlm.nih.gov/pubmed/19671150", "http://www.ncbi.nlm.nih.gov/pubmed/18039564", "http://www.ncbi.nlm.nih.gov/pubmed/18611950", "http://www.ncbi.nlm.nih.gov/pubmed/18469517", "http://www.ncbi.nlm.nih.gov/pubmed/16380414", "http://www.ncbi.nlm.nih.gov/pubmed/17029218", "http://www.ncbi.nlm.nih.gov/pubmed/22740507", "http://www.ncbi.nlm.nih.gov/pubmed/15889017", "http://www.ncbi.nlm.nih.gov/pubmed/22508983", "http://www.ncbi.nlm.nih.gov/pubmed/22484480", "http://www.ncbi.nlm.nih.gov/pubmed/20528922", "http://www.ncbi.nlm.nih.gov/pubmed/20194434", "http://www.ncbi.nlm.nih.gov/pubmed/23414597", "http://www.ncbi.nlm.nih.gov/pubmed/20807817", "http://www.ncbi.nlm.nih.gov/pubmed/11859407", "http://www.ncbi.nlm.nih.gov/pubmed/18256531", "http://www.ncbi.nlm.nih.gov/pubmed/23436675", "http://www.ncbi.nlm.nih.gov/pubmed/23362263", "http://www.ncbi.nlm.nih.gov/pubmed/23188674", "http://www.ncbi.nlm.nih.gov/pubmed/18583365", "http://www.ncbi.nlm.nih.gov/pubmed/21459846", "http://www.ncbi.nlm.nih.gov/pubmed/15752257", "http://www.ncbi.nlm.nih.gov/pubmed/16630058", "http://www.ncbi.nlm.nih.gov/pubmed/17430565", "http://www.ncbi.nlm.nih.gov/pubmed/18421303", "http://www.ncbi.nlm.nih.gov/pubmed/17047653", "http://www.ncbi.nlm.nih.gov/pubmed/17446929", "http://www.ncbi.nlm.nih.gov/pubmed/17912537", "http://www.ncbi.nlm.nih.gov/pubmed/15741235", "http://www.ncbi.nlm.nih.gov/pubmed/15467455", "http://www.ncbi.nlm.nih.gov/pubmed/16290057", "http://www.ncbi.nlm.nih.gov/pubmed/19103865", "http://www.ncbi.nlm.nih.gov/pubmed/19363520", "http://www.ncbi.nlm.nih.gov/pubmed/16980297", "http://www.ncbi.nlm.nih.gov/pubmed/17637683", "http://www.ncbi.nlm.nih.gov/pubmed/20613985" ], "ideal_answer": [ "The TP73 gene, due to the presence of two promoters (P1 and P2) in its 5' flanking region, encodes a fully transcriptionally active domain (TAp73) and the amino terminus deleted (\u0394Np73). TAp73 possesses pro-apoptotic properties, while deltaNp73 has anti-apoptotic functions. Alternative 3'-end splicing results in generation of at least seven TAp73 distinctive isoforms ( \u03b1, \u03b2, \u03b3, etc ).", "The Trp73 gene belongs to the p53 family of transcription factors and, like the other members, is transcribed into different isoforms [1-4]. TP73 gene contains two promoters, encoding the transcriptional domain-containing (TAp73) and the amino deleted (DNp73) isoforms [5, 6]. Furthermore alternative splicing at the 3'-end (to generate a, b, g, etc isoforms) and 5'-end (to generate D2, D3 and D2-3 isoforms) results in generation of at least 14 different transcripts, with different abilities to promote or repress apoptosis [7, 8]. (PMID: 22388545)" ], "exact_answer": [ "seven", "7" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020033" ], "type": "factoid", "id": "5173bdb38ed59a060a000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "A member of the p53 family, p73, has several isoforms and differentially regulates transcription of genes involved in the control of the cell cycle and apoptosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256531", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The p73 gene, a homologue of the p53 tumor suppressor, is expressed as TA and \u0394N isoforms. TAp73 has similar activity as p53 and functions as a tumor suppressor whereas \u0394Np73 has both pro- and anti-survival functions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852228", "endSection": "sections.0" }, { "offsetInBeginSection": 103, "offsetInEndSection": 316, "text": "Transcription from two different promoters on the p73 gene results in generation of transcriptionally active TAp73 isoforms and dominant negative DeltaNp73 isoforms with opposing pro- and anti-apoptotic functions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20615966", "endSection": "sections.0" }, { "offsetInBeginSection": 78, "offsetInEndSection": 426, "text": "We have evaluated the differential expression and subcellular localization of the functionally distinct apoptotic (TA) and anti-apoptotic (DeltaN) isoforms of p73 in non-small cell lung cancer (NSCLC), their possible association with p53 expression and determined the methylation status of the two p73 gene promoters (P1 and P2) in this tumor type.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19148480", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "The role of various p73 isoforms in tumorigenesis has been controversial. However, as we have recently shown, the generation of TAp73-deficient (TAp73(-/-)) mice reveals that TAp73 isoforms exert tumor-suppressive functions, indicating an emerging role for Trp-73 in the maintenance of genomic stability. Unlike mice lacking all p73 isoforms, TAp73(-/-) mice show a high incidence of spontaneous tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19139399", "endSection": "sections.0" }, { "offsetInBeginSection": 150, "offsetInEndSection": 445, "text": "Alternative promoters and N-terminal splicing result in the transcription and processing of either full-length (TA) or N-terminally truncated (deltaN) p73 isoforms. TAp73 possesses pro-apoptotic functions, while deltaNp73 has anti-apoptotic properties via functional inhibition of TAp73 and p53.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16980297", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The p73 gene is able to encode transcriptionaly active TAp73, as well as a dominant-negatively acting DeltaNp73 transcript isoforms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15138575", "endSection": "sections.0" }, { "offsetInBeginSection": 143, "offsetInEndSection": 333, "text": "Since some mutant p53 proteins and \u0394Np73 isoforms form heterocomplexes with TAp73, we asked whether p53 isoforms can do the same and potentially act as dominant-negative inhibitors of TAp73.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23188674", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "p73, a p53 family tumor suppressor, is expressed as TA and \u0394N isoforms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22508983", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "p73 is expressed as TA and \u0394N isoforms, both of which are implicated in tumor suppression and/or promotion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22457351", "endSection": "sections.0" }, { "offsetInBeginSection": 881, "offsetInEndSection": 971, "text": "We found that TAp73 isoforms are down regulated in oocytes from women older than 38 years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21946516", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "p73 possesses an extrinsic P1 promoter and an intrinsic P2 promoter controlling the expression of the pro-apoptotic TAp73 isoforms and the anti-apoptotic \u0394\u039dp73 isoforms respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20926182", "endSection": "sections.0" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1150, "text": "BRCA1-deficient ovarian carcinoma cells exhibit hypermethylation within a p73 regulatory region, which includes the binding site for the p73 transcriptional repressor ZEB1, leading to the abrogation of ZEB1 binding and increased expression of transactivating p73 isoforms (TAp73).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807817", "endSection": "sections.0" }, { "offsetInBeginSection": 359, "offsetInEndSection": 540, "text": "In this study, we investigated the expression and subcellular distribution of two N-terminal isoforms, TAp73 and \u0394Np73, in medulloblastoma cells using immunofluorescence microscopy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20803057", "endSection": "sections.0" }, { "offsetInBeginSection": 409, "offsetInEndSection": 600, "text": "Proteasomal degradation of p73 is mediated by polyubiquitination-dependent and -independent processes both of which appear, thus far, to lack selectivity for the TAp73 and DeltaNp73 isoforms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20615966", "endSection": "sections.0" }, { "offsetInBeginSection": 218, "offsetInEndSection": 406, "text": "In general, TAp73 isoforms show proapoptotic activities, whereas members of the N-terminally truncated (\u0394N) p73 subfamily that lack the transactivation domain show antiapoptotic functions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581467", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The p73 gene possesses an extrinsic P1 promoter and an intrinsic P2 promoter, resulting in TAp73 and DeltaNup73 isoforms, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20528922", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence of all TAp73 and DeltaNp73 isoforms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20194434", "endSection": "sections.0" }, { "offsetInBeginSection": 713, "offsetInEndSection": 822, "text": "Moreover, we also found that subcellular location of p73 isoforms changes with the culture density increases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19885566", "endSection": "sections.0" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1271, "text": "Moreover, ectopic expression of DeltaNp73alpha (but not other p73 isoforms) increased alphaB-crystallin mRNA levels in the absence of p53.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777343", "endSection": "sections.0" }, { "offsetInBeginSection": 329, "offsetInEndSection": 437, "text": "Like wt p53, TAp63 and TAp73 isoforms transactivate target genes that activate apoptosis signaling pathways.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19615968", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The TP73 gene gives rise to transactivation domain-p73 isoforms (TAp73) as well as DeltaNp73 variants with a truncated N terminus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509292", "endSection": "sections.0" }, { "offsetInBeginSection": 225, "offsetInEndSection": 344, "text": "In contrast, antiapoptotic DeltaNp73 isoforms lack the TA domain and are dominant-negative inhibitors of p53 and TAp73.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19363520", "endSection": "sections.0" }, { "offsetInBeginSection": 125, "offsetInEndSection": 336, "text": "The isoforms TAp63 and TAp73 transactivate p53 target genes and induce apoptosis, whereas the isoforms DeltaNp63 and DeltaNp73 lack transactivation and might have dominant-negative effects in p53 family members.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19103865", "endSection": "sections.0" }, { "offsetInBeginSection": 347, "offsetInEndSection": 602, "text": "The expression of all 5 N-terminal isoforms (TAp73, DeltaNp73, DeltaN'p73, Ex2p73 and Ex2/3p73) was measured by real-time RT-PCR and p53 status was analyzed by immunohistochemistry. TAp73, DeltaNp73 and DeltaN'p73 were significantly upregulated in tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16964385", "endSection": "sections.0" }, { "offsetInBeginSection": 552, "offsetInEndSection": 734, "text": "Consequently, different p73 isoforms can be degraded by calpains, i.e., both N-terminal isoforms (TAp73 and DeltaNp73) as well as the C-terminal isoforms (alpha, beta, gamma, delta).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15975558", "endSection": "sections.0" }, { "offsetInBeginSection": 218, "offsetInEndSection": 343, "text": "Variants lacking the TA domain (DeltaN isoforms) are induced by TAp73 and by p53, and inhibit their transcriptional activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15781249", "endSection": "sections.0" }, { "offsetInBeginSection": 429, "offsetInEndSection": 675, "text": "Indeed, tazarotene modulates the expression of the p73 gene in immortalized keratinocyte cell lines by inducing the pro-apoptotic and anti-proliferative TAp73 isoforms and by repressing the anti-apoptotic and pro-proliferative DeltaNp73 isoforms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15610529", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "p73, the first p53 gene homologue, encodes an array of p73 proteins including p73 alpha full-length (TAp73 alpha) and amino-truncated isoforms (Delta Np73 alpha), two proteins with opposite biological functions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14676279", "endSection": "sections.0" }, { "offsetInBeginSection": 329, "offsetInEndSection": 567, "text": "We further showed that DeltaNp73 is a potent transdominant inhibitor of wild-type p53 and TAp73 in cultured human tumor cells by efficiently counteracting their target gene transactivations, apoptosis, and growth suppression functions (A.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12897129", "endSection": "sections.0" }, { "offsetInBeginSection": 216, "offsetInEndSection": 408, "text": "In developing sympathetic neurons of mice, p73 is predominantly expressed as a truncated anti-apoptotic isoform (DeltaNp73), which antagonizes both p53 and the full-length p73 protein (TAp73).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11859407", "endSection": "sections.0" }, { "offsetInBeginSection": 1358, "offsetInEndSection": 1561, "text": "Interestingly, expression of the Delta Np73 is strongly up-regulated by the TA isoforms and by p53, thus creating a feedback loop that tightly regulates the function of TAp73 and more importantly of p53.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11753569", "endSection": "sections.0" } ] }, { "body": "Is the yeast \u039cac1 transcription factor induced upon copper deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "http://www.ncbi.nlm.nih.gov/pubmed/9159110", "http://www.ncbi.nlm.nih.gov/pubmed/9430656", "http://www.ncbi.nlm.nih.gov/pubmed/10922376", "http://www.ncbi.nlm.nih.gov/pubmed/18977757", "http://www.ncbi.nlm.nih.gov/pubmed/22683637", "http://www.ncbi.nlm.nih.gov/pubmed/21489137" ], "ideal_answer": [ "In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003300", "http://amigo.geneontology.org/amigo/term/GO:0046688" ], "type": "yesno", "id": "56e19eba51531f7e33000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Low-affinity copper transporter CTR2 is regulated by copper-sensing transcription factor Mac1p in Saccharomyces cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "endSection": "title" }, { "offsetInBeginSection": 766, "offsetInEndSection": 895, "text": "The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1415, "text": "Taken together, our results suggest that Mac1p can activate the expression of vacuolar copper transporter Ctr2p in response to copper deficiency, resulting in yeast resistance to copper starvation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 568, "text": "The ablation of either MAC1 or AFT1 also abrogated CTR2 expression induced by copper depletion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683637", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 765, "text": "Our further study revealed that exogenous Aft1p upregulates CTR2 transcription only in the presence of Mac1p, whereas exogenous Mac1p upregulates CTR2 transcription only in the presence of Aft1p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683637", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 233, "text": "We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683637", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 455, "text": "In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18977757", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 680, "text": "Although Mac1 activates the transcription of genes involved in high affinity copper uptake during periods of deficiency, little is known about the mechanisms by which Mac1 senses or responds to reduced copper availability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18977757", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1232, "text": "The catalytic activity of Sod1 is essential for Mac1 activation and promotes a regulated increase in binding of Mac1 to copper response elements in the promoter regions of genomic Mac1 target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18977757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10922376", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 299, "text": "Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10922376", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1604, "text": "Taken together, our results suggest that Mac1p can activate the expression of vacuolar copper transporter Ctr2p in response to copper deficiency, resulting in yeast resistance to copper starvation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 594, "text": "In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18977757", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 351, "text": "We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683637", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 461, "text": "The yeast Mac1 protein is a copper-sensing transcription factor that is essential for both the activation and inactivation of genes required for high affinity copper ion transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9430656", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 897, "text": "The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Copper-mediated repression of the activation domain in the yeast Mac1p transcription factor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9159110", "endSection": "title" }, { "offsetInBeginSection": 114, "offsetInEndSection": 234, "text": "We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683637", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 897, "text": "In this study, we found that copper depletion can upregulate yeast CTR2 gene transcription while copper overload downregulate it. The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "endSection": "abstract" } ] }, { "body": "What is the mechanism of DNA replication termination in vertebrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26322582" ], "ideal_answer": [ "Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly. DNA synthesis does not slow detectably as forks approach each other, and leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:2000621", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/amigo/term/GO:0097047", "http://amigo.geneontology.org/amigo/term/GO:0071170", "http://www.uniprot.org/uniprot/RTP_BACPZ", "http://www.uniprot.org/uniprot/RTP_BACVA", "http://amigo.geneontology.org/amigo/term/GO:0006274", "http://amigo.geneontology.org/amigo/term/GO:0071946" ], "type": "summary", "id": "56a8b1a5a17756b72f000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26322582", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 1171, "text": "We show that DNA synthesis does not slow detectably as forks approach each other, and that leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26322582", "endSection": "abstract" } ] }, { "body": "Which are the different members/isoforms of the Ras oncogenes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24194124", "http://www.ncbi.nlm.nih.gov/pubmed/21924373", "http://www.ncbi.nlm.nih.gov/pubmed/22648805", "http://www.ncbi.nlm.nih.gov/pubmed/21779492", "http://www.ncbi.nlm.nih.gov/pubmed/23103856", "http://www.ncbi.nlm.nih.gov/pubmed/21779495", "http://www.ncbi.nlm.nih.gov/pubmed/22981836", "http://www.ncbi.nlm.nih.gov/pubmed/24247240", "http://www.ncbi.nlm.nih.gov/pubmed/22589270", "http://www.ncbi.nlm.nih.gov/pubmed/17671181", "http://www.ncbi.nlm.nih.gov/pubmed/23412389", "http://www.ncbi.nlm.nih.gov/pubmed/23496764", "http://www.ncbi.nlm.nih.gov/pubmed/23871832" ], "ideal_answer": [ "Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions.", "H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B)" ], "exact_answer": [ [ "H-Ras" ], [ "N-Ras" ], [ "K-Ras4A" ], [ "K-Ras4B" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020033", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011905", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005099", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015689", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018631", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016283" ], "type": "list", "id": "5518e817622b194345000006", "snippets": [ { "offsetInBeginSection": 135, "offsetInEndSection": 172, "text": "The major Ras isoforms (K, H, and N) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Mutations in Ras isoforms such as K-Ras, N-Ras, and H-Ras contribute to roughly 85, 15, and 1% of human cancers, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194124", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 249, "text": "the Ras isoforms (H, N and K) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23871832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "The mutant forms of KRas, NRas and HRas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23496764", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 190, "text": " lipidated Ras isoforms (H-Ras and N-Ras)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23412389", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 134, "text": ": H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23103856", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 327, "text": "Human tumours frequently express Ras proteins (Ha-, Ki-, N-Ras) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981836", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 175, "text": " There are three major ras isoforms: H-, N- and K-Ras. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22648805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589270", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 132, "text": "hree closely related isoforms, HRAS, KRAS and NRAS, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21924373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21779495", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 422, "text": "he 3 Ras isoforms-H-Ras, K-Ras, and N-Ras-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21779492", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 980, "text": "In this study, we compared the leukemogenic potential of activated NRAS, KRAS, and HRAS in the same bone marrow transduction/transplantation model system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671181", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 134, "text": "H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23103856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 437, "text": "Ras proteins are small GTPase functioning as molecular switches that, in response to particular extracellular signalling, as growth factors, activate a diverse array of intracellular effector cascades regulating cell proliferation, differentiation and apoptosis. Human tumours frequently express Ras proteins (Ha-, Ki-, N-Ras) activated by point mutations which contribute to malignant phenotype, including invasiveness and angiogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Ras small GTPases function as transducers of extracellular signals regulating cell survival, growth and differentiation. There are three major ras isoforms: H-, N- and K-Ras. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22648805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21924373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21779495", "endSection": "abstract" } ] }, { "body": "Which is the subcellular localization of ERAP2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23988446", "http://www.ncbi.nlm.nih.gov/pubmed/23946506", "http://www.ncbi.nlm.nih.gov/pubmed/16054015" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/A6QPT7", "o": 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}, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17731032", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17746860", "o": "HUGO" } ], "ideal_answer": [ "Endoplasmic reticulum aminopeptidase 2 (ERAP2) is localized to the luminal side of the endoplasmic reticulum." ], "exact_answer": [ "luminal side of the endoplasmic reticulum" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060341", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008104", "http://www.uniprot.org/uniprot/ERAP2_PONAB", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051179", "http://www.uniprot.org/uniprot/ERAP2_HUMAN", "http://www.uniprot.org/uniprot/ERAP2_BOVIN" ], "type": "factoid", "id": "53442ca9aeec6fbd0700000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "The human endoplasmic reticulum aminopeptidase (ERAP) 1 and 2 proteins ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23946506", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 329, "text": "They are categorized as a unique class of proteases based on their subcellular localization on the luminal side of the endoplasmic reticulum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23946506", "endSection": "abstract" }, { "offsetInBeginSection": 22, "offsetInEndSection": 69, "text": "endoplasmic reticulum aminopeptidase 2 (ERAP2) ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23988446", "endSection": "title" }, { "offsetInBeginSection": 740, "offsetInEndSection": 808, "text": "ERAP2 is a proteolytic enzyme set in the endoplasmic reticulum (ER) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23988446", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 592, "text": "both A-LAP and L-RAP are retained in the endoplasmic reticulum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16054015", "endSection": "abstract" } ] }, { "body": "Have thyronamines effects on fat tissue?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17912534", "http://www.ncbi.nlm.nih.gov/pubmed/17204552", "http://www.ncbi.nlm.nih.gov/pubmed/6094171", "http://www.ncbi.nlm.nih.gov/pubmed/20880963", "http://www.ncbi.nlm.nih.gov/pubmed/20005733", "http://www.ncbi.nlm.nih.gov/pubmed/18486124", "http://www.ncbi.nlm.nih.gov/pubmed/19273499", "http://www.ncbi.nlm.nih.gov/pubmed/22016721", "http://www.ncbi.nlm.nih.gov/pubmed/21664427", "http://www.ncbi.nlm.nih.gov/pubmed/19116337", "http://www.ncbi.nlm.nih.gov/pubmed/21490071", "http://www.ncbi.nlm.nih.gov/pubmed/17579492" ], "ideal_answer": [ "There is not clear evidence that thyronamines have direct effect on adipose tissue" ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000273", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050153", "http://www.biosemantics.org/jochem#4251308", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019358", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014024", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005218", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005223", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017667" ], "type": "yesno", "id": "532c147bd6d3ac6a3400001e", "snippets": [ { "offsetInBeginSection": 1523, "offsetInEndSection": 1598, "text": "In conclusion, trace amines and thyronamines are negative inotropic agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18486124", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 229, "text": "Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21664427", "endSection": "abstract" } ] }, { "body": "What are the names of anti-CD52 monoclonal antibody that is used for treatment of multiple sclerosis patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23122652", "http://www.ncbi.nlm.nih.gov/pubmed/23122650", "http://www.ncbi.nlm.nih.gov/pubmed/19296065", "http://www.ncbi.nlm.nih.gov/pubmed/10482259", "http://www.ncbi.nlm.nih.gov/pubmed/20236038", "http://www.ncbi.nlm.nih.gov/pubmed/7914262", "http://www.ncbi.nlm.nih.gov/pubmed/15049789", "http://www.ncbi.nlm.nih.gov/pubmed/24116901", "http://www.ncbi.nlm.nih.gov/pubmed/23558379", "http://www.ncbi.nlm.nih.gov/pubmed/24289293", "http://www.ncbi.nlm.nih.gov/pubmed/18283404", "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "http://www.ncbi.nlm.nih.gov/pubmed/18713579", "http://www.ncbi.nlm.nih.gov/pubmed/19740383", "http://www.ncbi.nlm.nih.gov/pubmed/21550857", "http://www.ncbi.nlm.nih.gov/pubmed/22229582", "http://www.ncbi.nlm.nih.gov/pubmed/22056965", "http://www.ncbi.nlm.nih.gov/pubmed/20088763", "http://www.ncbi.nlm.nih.gov/pubmed/18946064", "http://www.ncbi.nlm.nih.gov/pubmed/18075272", "http://www.ncbi.nlm.nih.gov/pubmed/24198283", "http://www.ncbi.nlm.nih.gov/pubmed/16231285", "http://www.ncbi.nlm.nih.gov/pubmed/8624684", "http://www.ncbi.nlm.nih.gov/pubmed/23759318", "http://www.ncbi.nlm.nih.gov/pubmed/24170099", "http://www.ncbi.nlm.nih.gov/pubmed/23494602", "http://www.ncbi.nlm.nih.gov/pubmed/23459567", "http://www.ncbi.nlm.nih.gov/pubmed/22252465", "http://www.ncbi.nlm.nih.gov/pubmed/23634277", "http://www.ncbi.nlm.nih.gov/pubmed/21899662", "http://www.ncbi.nlm.nih.gov/pubmed/23709214", "http://www.ncbi.nlm.nih.gov/pubmed/10568572", "http://www.ncbi.nlm.nih.gov/pubmed/17920549", "http://www.ncbi.nlm.nih.gov/pubmed/19878629" ], "ideal_answer": [ "Alemtuzumab and Campath-1H are the names of anti-CD52 monoclonal antibody that is used for treatment of multiple sclerosis patients. It has been shown to be effective for treatment naive and treatment resistant multiple sclerosis patients." ], "exact_answer": [ [ "Alemtuzumab" ], [ "Campath-1H" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103", "http://www.disease-ontology.org/api/metadata/DOID:2377", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000911" ], "type": "list", "id": "530cefaaad0bf1360c000003", "snippets": [ { "offsetInBeginSection": 1395, "offsetInEndSection": 1556, "text": "Alemtuzumab offers induction strategy for very active relapsing MS patients who have failed conventional therapy, and possibly selected treatment-naive patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198283", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression in relapsing-remitting multiple sclerosis (RRMS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198283", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 169, "text": "Alemtuzumab, an anti-CD52 monoclonal antibody, increased the risk of thyroid dysfunction in CAMMS223, a phase 2 trial in relapsing-remitting multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170099", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1314, "text": "Since then, one phase II and two phase III trials have shown that alemtuzumab reduces the relapse rate, compared with the active comparator interferon beta-1a (IFN\u03b2-1a), in treatment-na\u00efve and treatment-experienced MS up to 10 years from disease onset. Furthermore, in two of these trials, alemtuzumab reduced the risk of accumulating disability compared with IFN\u03b2-1a; indeed alemtuzumab treatment led to an improvement in disability and reduction in cerebral atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23709214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Alemtuzumab is a humanized monoclonal antibody specific for the CD52 protein present at high levels on the surface of B and T lymphocytes. In clinical trials, alemtuzumab has shown a clinical benefit superior to that of interferon-\u03b2 in relapsing-remitting multiple sclerosis patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24116901", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 696, "text": "These results potentially help explain the level of immunocompetence observed in alemtuzumab-treated MS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23759318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Alemtuzumab was first used in multiple sclerosis in 1991. It is a monoclonal antibody which is directed against CD52, a protein of unknown function on lymphocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23634277", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 784, "text": "Against an active comparator and the current first-line therapy for relapsing-remitting multiple sclerosis (interferon-beta), alemtuzumab showed a significant reduction in annualized relapse rate as well as a significant reduction in the accumulation of disability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23558379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Alemtuzumab (previously known as Campath(\u00ae)) is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23494602", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 1060, "text": "Compared to interferon beta-1a, alemtuzumab reduced the relapse rate by 49%-74% (P < 0.0001), and in two studies it reduced the risk of sustained disability accumulation by 42%-71% (P < 0.01). In one study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CARE-MS1), there was no significant difference compared to interferon, perhaps reflecting the surprisingly low frequency of disability events in the comparator group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23494602", "endSection": "abstract" }, { "offsetInBeginSection": 2103, "offsetInEndSection": 2222, "text": "Alemtuzumab has been submitted for licensing in relapsing-remitting multiple sclerosis in the United States and Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23494602", "endSection": "abstract" }, { "offsetInBeginSection": 1513, "offsetInEndSection": 1665, "text": "Alemtuzumab was associated with a greater chance of improved contrast sensitivity in patients with RRMS and may delay the worsening of visual function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23459567", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 180, "text": "The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122652", "endSection": "abstract" }, { "offsetInBeginSection": 2640, "offsetInEndSection": 2919, "text": "Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 473, "text": "Alemtuzumab, formally known as Campath-1H, is a humanized monoclonal antibody directed against CD52, a protein on the surface of lymphocytes and monocytes with unknown function. A single dose of alemtuzumab leads to a rapid, profound and prolonged lymphopenia. A Phase II trial has shown that alemtuzumab reduces the risk of relapse and accumulation of disability by over 70% compared with interferon beta in patients with early relapsing-remitting multiple sclerosis (MS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19878629", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 963, "text": "Alemtuzumab, targeting CD52 expressed on T-cells, B-cells, monocytes and macrophages, has also shown to be effective in early RRMS and phase III trials are currently ongoing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20088763", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 1000, "text": "monoclonal antibody therapy has provided the opportunity to rationally direct the therapeutic intervention by specifically targeting mechanisms of the immune system such as CD52 (alemtuzumab), CD25 (daclizumab), VLA-4 (natalizumab) and CD20 (rituximab)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20236038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Alemtuzumab is a humanized monoclonal antibody targeting CD52, a broadly expressed cell surface molecule on immune cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21550857", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 441, "text": "Alemtuzumab-treatment of MS patients with relapsing-remitting forms of the disease significantly reduced the risk of relapse and accumulation of disability compared to interferon \u03b2-1a treatment in a phase II trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21550857", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 181, "text": "Alemtuzumab (CD52-specific humanized monoclonal antibody) was found to be an effective therapy for treatment-naive patients with relapsing-remitting multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21899662", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1633, "text": "Alemtuzumab effectively reduced relapse rates and improved clinical scores in patients with active relapsing-remitting multiple sclerosis not controlled by interferon therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21899662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Alemtuzumab is an anti-CD52 monoclonal antibody with remarkable efficacy in relapsing multiple sclerosis (MS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22252465", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 161, "text": "The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122650", "endSection": "abstract" }, { "offsetInBeginSection": 2454, "offsetInEndSection": 2636, "text": "For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122650", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1221, "text": "Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10568572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Campath-1H is a humanized monoclonal antibody directed at CD52 expressed on lymphocytes and other cells of the immune system. It has been tested extensively in lymphoid malignancies, autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and organ transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15049789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 563, "text": "Campath 1-H (Alemtuzumab) is a humanised monoclonal antibody which targets the CD52 antigen, a low molecular weight glycoprotein present on the surface of most lymphocyte lineages, causing complement mediated lysis and rapid and prolonged T lymphocyte depletion. Following encouraging initial data from other centres we report our open label experience of using Campath 1-H as a treatment in aggressive relapsing multiple sclerosis in a consecutive series of 39 highly selected patients treated across three regional centres and followed for a mean of 1.89 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18283404", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "Alemtuzumab, a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes, may be an effective treatment for early multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18946064", "endSection": "abstract" }, { "offsetInBeginSection": 2023, "offsetInEndSection": 2242, "text": "In patients with early, relapsing-remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18946064", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 1019, "text": "Alemtuzumab, a monoclonal antibody targeting CD52, is a highly promising agent currently being studied in two phase III clinical trials. In this review, data from the recently published phase II clinical trial in the treatment of early relapsing remitting MS is summarized and analyzed in light of the development of alemtuzumab for MS and its potential role in treating this disease is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19296065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on the surface of normal and malignant lymphocytes. It is approved for the treatment of B-cell chronic lymphocytic leukaemia and is undergoing Phase III clinical trials for the treatment of multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19740383", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 422, "text": "To assess the effect of systemic lymphocyte depletion on disease activity, seven patients with MS received a 10-day intravenous course of the humanised monoclonal antibody CAMPATH-1H (anti-CDw52).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7914262", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1423, "text": "The effect of CAMPATH-1H on disease activity provides direct, but preliminary, evidence that disease activity in MS depends on the availability of circulating lymphocytes and can be prevented by lymphocyte depletion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7914262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "The elective treatment of patients with multiple sclerosis, using a humanized anti-leukocyte (CD52) monoclonal antibody (Campath-1H), has illuminated mechanisms that underlie the clinical course of the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10482259", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 544, "text": "Alemtuzumab is currently under review to treat relapsing multiple sclerosis (MS) in the United States, based on positive Phase II and Phase III trials in both treatment-na\u00efve and treated relapsing MS patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289293", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 881, "text": "Alemtuzumab has recently been approved by the European authorities for active relapsing MS, in essence as a first-line agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Alemtuzumab is a humanized monoclonal antibody directed against CD52. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23709214", "endSection": "abstract" } ] }, { "body": "Is there a package in R/bioconductor for classification of alternative splicing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24655717" ], "ideal_answer": [ "Yes. SpliceR is an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398", "http://amigo.geneontology.org/amigo/term/GO:0000381", "http://amigo.geneontology.org/amigo/term/GO:0000380" ], "type": "yesno", "id": "56d19ffaab2fed4a47000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 345, "text": "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 999, "text": "spliceR uses the full-length transcript output from RNA-seq assemblers to detect single or multiple exon skipping, alternative donor and acceptor sites, intron retention, alternative first or last exon usage, and mutually exclusive exon events. For each of these events spliceR also annotates the genomic coordinates of the differentially spliced elements, facilitating downstream sequence analysis. For each transcript isoform fraction values are calculated to identify transcript switching between conditions. Lastly, spliceR predicts the coding potential, as well as the potential nonsense mediated decay (NMD) sensitivity of each transcript.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 524, "text": "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 346, "text": "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 334, "text": "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "abstract" } ] }, { "body": "Which brain structures have been investigated as potential targets for deep brain stimulation of patients suffering from major depression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24112897", "http://www.ncbi.nlm.nih.gov/pubmed/23230531", "http://www.ncbi.nlm.nih.gov/pubmed/22473055", "http://www.ncbi.nlm.nih.gov/pubmed/17429407", "http://www.ncbi.nlm.nih.gov/pubmed/21736514", "http://www.ncbi.nlm.nih.gov/pubmed/19284243", "http://www.ncbi.nlm.nih.gov/pubmed/15481726", "http://www.ncbi.nlm.nih.gov/pubmed/16816792", "http://www.ncbi.nlm.nih.gov/pubmed/19137233", "http://www.ncbi.nlm.nih.gov/pubmed/17498883", "http://www.ncbi.nlm.nih.gov/pubmed/19092783", "http://www.ncbi.nlm.nih.gov/pubmed/19727257", "http://www.ncbi.nlm.nih.gov/pubmed/18704495" ], "ideal_answer": [ "Subgenual cingulate gyrus, the anterior limb of the capsula interna, nucleus accumbens, medial forebrain bundle, habenula, and caudate nucleus have been investigated as potential targeted for the deep brain stimulation of patients suffering from major depression." ], "exact_answer": [ [ "subgenual cingulate gyrus" ], [ "anterior limb of the capsula interna" ], [ "nucleus accumbens" ], [ "medial forebrain bundle" ], [ "habenula" ], [ "ventral caudate nucleus" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003865", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046690", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001921", "http://www.disease-ontology.org/api/metadata/DOID:1470" ], "type": "list", "id": "530cefaaad0bf1360c000002", "snippets": [ { "offsetInBeginSection": 200, "offsetInEndSection": 516, "text": "Deep brain stimulation (DBS) is under scientific evaluation as a new treatment option for these treatment-resistant patients. First clinical studies with small samples have been stimulated at the subgenual cingulate gyrus (Cg25/24), the anterior limb of the capsula interna (ALIC), and the nucleus accumbens (NAcc). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24112897", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1017, "text": "New hypothesis-guided targets (e.g., medial forebrain bundle, habenula) are about to be assessed in clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24112897", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 168, "text": "Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) has antidepressant effects in patients suffering from treatment-resistant depression (TRD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21736514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "The ventral striatum, including the head of the caudate nucleus and the nucleus accumbens, is a putative target for deep brain stimulation (DBS) in the treatment of obsessive-compulsive disorder (OCD) and major depression (MD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19284243", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1672, "text": "High frequency stimulation was successfully applied in several small samples of patients with treatment-resistant depression when the stimulation focused on different areas, e.g., nucleus accumbens, the lateral habenula or cortical areas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19137233", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 485, "text": "We recorded electrophysiological activity directly from the nucleus accumbens of five patients undergoing deep brain stimulation for treatment of refractory major depression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19092783", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1131, "text": "Functional inhibition of the lateral habenula via deep brain stimulation (DBS) has antidepressive properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17498883", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 504, "text": "Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17429407", "endSection": "abstract" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 1831, "text": "These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17429407", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1380, "text": "Deep brain stimulation of the ventral caudate nucleus markedly improved symptoms of depression and anxiety until their remission, which was achieved at 6 months after the start of stimulation (HDRS < or = 7 and HARS < or = 10).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15481726", "endSection": "abstract" }, { "offsetInBeginSection": 1572, "offsetInEndSection": 1773, "text": "No neuropsychological deterioration was observed, indicating that DBS of the ventral caudate nucleus could be a promising strategy in the treatment of refractory cases of both OCD and major depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15481726", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 710, "text": "Comparisons of clinical outcomes and anatomical data on electrode positioning showed that caudate nucleus stimulation preferentially alleviated OCD manifestations, whereas nucleus accumbens stimulation improved depressive symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19284243", "endSection": "abstract" } ] }, { "body": "Is alemtuzumab effective for remission induction in patients diagnosed with T-cell prolymphocytic leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15453953", "http://www.ncbi.nlm.nih.gov/pubmed/17118783", "http://www.ncbi.nlm.nih.gov/pubmed/15757437", "http://www.ncbi.nlm.nih.gov/pubmed/12950233", "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "http://www.ncbi.nlm.nih.gov/pubmed/23211022", "http://www.ncbi.nlm.nih.gov/pubmed/16720203", "http://www.ncbi.nlm.nih.gov/pubmed/16645226", "http://www.ncbi.nlm.nih.gov/pubmed/22517037", "http://www.ncbi.nlm.nih.gov/pubmed/22649104", "http://www.ncbi.nlm.nih.gov/pubmed/11535503", "http://www.ncbi.nlm.nih.gov/pubmed/11986948", "http://www.ncbi.nlm.nih.gov/pubmed/23645660", "http://www.ncbi.nlm.nih.gov/pubmed/15869731", "http://www.ncbi.nlm.nih.gov/pubmed/21948296", "http://www.ncbi.nlm.nih.gov/pubmed/10561018", "http://www.ncbi.nlm.nih.gov/pubmed/23233647" ], "ideal_answer": [ "Yes, alemtuzumab (anti-CD52, Campath-1H) is effective for remission induction in patients diagnosed with T-cell prolymphocytic leukemia. Alemtuzumab can be administered in combination with other chemotherapeutic agents or as mono-therapy. Response rate to alemtuzumab is more than 90%. Alemtuzumab therapy is associated with improved survival of T-cell prolymphocytic leukemia patients." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4002029", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012074" ], "type": "yesno", "id": "530cefaaad0bf1360c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "endSection": "title" }, { "offsetInBeginSection": 131, "offsetInEndSection": 318, "text": "A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "endSection": "abstract" }, { "offsetInBeginSection": 1489, "offsetInEndSection": 1581, "text": "FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 773, "text": "Currently, the best treatment for T-PLL is IV alemtuzumab, which has resulted in very high response rates of more than 90% when given as frontline treatment and a significant improvement in survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23233647", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 906, "text": "The patient failed to respond to standard ALL induction chemotherapy, but achieved complete remission following treatment with a fludarabine and alemtuzumab-based regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23211022", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 401, "text": "Here we present a rare case of concurrent T-PLL and Kaposi sarcoma who achieved a complete hematologic and cytogenetic remission after a very short course of treatment with alemtuzumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22517037", "endSection": "abstract" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1243, "text": " Recent studies with single-agent alemtuzumab, an anti-CD52 monoclonal antibody, have shown improved response rates and survival in patients with T-cell prolymphocytic leukemia and cutaneous T-cell lymphoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16720203", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 696, "text": "The CD52 antigen is expressed at high density on the malignant T-cells and therapy with alemtuzumab, a humanized IgG1 antibody that targets this antigen, has produced promising results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16645226", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 707, "text": "With the introduction of alemtuzumab, most patients who progressed despite treatment with pentostatin had a major response with a complete remission rate higher than that obtained with pentostatin when used as a first line.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15869731", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 227, "text": "Alemtuzumab (anti-CD52, Campath-1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B-cell chronic lymphocytic leukemia and T-cell prolymphocytic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12950233", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 384, "text": "Here we report the outcome of two patients with CD4-positive T cell prolymphocytic leukemia treated with CAMPATH-1H. Both patients responded rapidly to treatment and subsequently developed CD4 lymphopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11986948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a median survival of 7.5 months. Preliminary results indicated a high remission induction rate with the human CD52 antibody, CAMPATH-1H. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11535503", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 738, "text": "CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal response. The overall response rate was 76% with 60% CR and 16% partial remission (PR). These responses were durable with a median disease-free interval of 7 months (range, 4-45 months). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11535503", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1570, "text": "The conclusion is that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11535503", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1343, "text": "For example, most patients with T-cell prolymphocytic leukemia, including those with large tumor burdens and high peripheral white blood cell counts, will enter complete remission using the antibody CAMPATH-1H without any evidence of tumor lysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10561018", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1006, "text": "Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "endSection": "abstract" } ] }, { "body": "What is the association between moon cycle and rupture risk of intracranial aneurysms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19101078", "http://www.ncbi.nlm.nih.gov/pubmed/18353534", "http://www.ncbi.nlm.nih.gov/pubmed/23702791" ], "ideal_answer": [ "It has been reported that moon phases correlate with the incidence of aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysms. However, other authors have found no correlation between incidence of aneurysmal SAH, location of the aneurysm, initial clinical presentation, or amount of subarachnoid blood and the lunar cycle." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10941", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002532", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016081", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017542" ], "type": "summary", "id": "530cefaaad0bf1360c000006", "snippets": [ { "offsetInBeginSection": 115, "offsetInEndSection": 288, "text": "Recently, it has been reported that moon phases correlate with the incidence of aneurysmal subarachnoid hemorrhage (SAH), however, another author found no such association. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23702791", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 949, "text": "We found no correlation between incidence of aneurysmal SAH, location of the aneurysm, initial clinical presentation, or amount of subarachnoid blood and the lunar cycle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23702791", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1106, "text": "The moon influences neither the incidence of aneurysmal SAH nor the grade of initial neurological deterioration or amount of subarachnoid blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23702791", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 502, "text": "We did not observe any significant impact of the lunar cycle on the incidence of aneurysmal subarachnoid haemorrhage in 717 consecutive patients (p=0.84).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19101078", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 615, "text": "The impact of the lunar cycle on aneurysmal subarachnoid haemorrhage is a myth rather than reality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19101078", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 520, "text": "An incidence peak for aneurysm rupture (28 patients) was seen during the phase of new moon, which was statistically significant (p < 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18353534", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 763, "text": "The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18353534", "endSection": "abstract" } ] }, { "body": "Is there an association between TERT promoter mutation and survival of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23393205", "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "http://www.ncbi.nlm.nih.gov/pubmed/23955565" ], "ideal_answer": [ "Telomerase reverse transcriptase (TERT) promoter are associated with shorter survival of glioblastoma patients. Prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3073" ], "type": "yesno", "id": "55032bbfe9bde69634000032", "snippets": [ { "offsetInBeginSection": 993, "offsetInEndSection": 1734, "text": "Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs. 10.5 months; P = 0.015) and multivariate analysis after adjusting for age and gender (HR 1.38, 95 % CI 1.01-1.88, P = 0.041). However, TERT mutations had no significant impact on patients' survival in multivariate analysis after further adjusting for other genetic alterations, or when primary and secondary glioblastomas were separately analysed. These results suggest that the prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations, which are a significant prognostic marker of better survival in patients with secondary glioblastomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955565", "endSection": "abstract" }, { "offsetInBeginSection": 1593, "offsetInEndSection": 1825, "text": "Patients with tumors lacking hTERT expression/TA showed a significant survival benefit (Kaplan-Meier test, both P < .01), which, however, was based exclusively on the younger patient subgroup (\u226460 y, both P < .005; >60 y, both ns). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393205", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1133, "text": "Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955565", "endSection": "abstract" } ] }, { "body": "Is bapineuzumab effective for treatment of patients with Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20189881", "http://www.ncbi.nlm.nih.gov/pubmed/21263194", "http://www.ncbi.nlm.nih.gov/pubmed/24255592", "http://www.ncbi.nlm.nih.gov/pubmed/22357853", "http://www.ncbi.nlm.nih.gov/pubmed/24086465", "http://www.ncbi.nlm.nih.gov/pubmed/24216217", "http://www.ncbi.nlm.nih.gov/pubmed/20929585", "http://www.ncbi.nlm.nih.gov/pubmed/24434253", "http://www.ncbi.nlm.nih.gov/pubmed/23861639", "http://www.ncbi.nlm.nih.gov/pubmed/22529838", "http://www.ncbi.nlm.nih.gov/pubmed/19674435", "http://www.ncbi.nlm.nih.gov/pubmed/23299380", "http://www.ncbi.nlm.nih.gov/pubmed/22506132", "http://www.ncbi.nlm.nih.gov/pubmed/23582316", "http://www.ncbi.nlm.nih.gov/pubmed/23847530", "http://www.ncbi.nlm.nih.gov/pubmed/21091109", "http://www.ncbi.nlm.nih.gov/pubmed/23555764", "http://www.ncbi.nlm.nih.gov/pubmed/21592055", "http://www.ncbi.nlm.nih.gov/pubmed/22815077", "http://www.ncbi.nlm.nih.gov/pubmed/23874844", "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "http://www.ncbi.nlm.nih.gov/pubmed/23894286", "http://www.ncbi.nlm.nih.gov/pubmed/20205639", "http://www.ncbi.nlm.nih.gov/pubmed/23931438", "http://www.ncbi.nlm.nih.gov/pubmed/23809364", "http://www.ncbi.nlm.nih.gov/pubmed/20154508", "http://www.ncbi.nlm.nih.gov/pubmed/23210837", "http://www.ncbi.nlm.nih.gov/pubmed/23599675", "http://www.ncbi.nlm.nih.gov/pubmed/19585948", "http://www.ncbi.nlm.nih.gov/pubmed/20388189", "http://www.ncbi.nlm.nih.gov/pubmed/20497044", "http://www.ncbi.nlm.nih.gov/pubmed/23416764", "http://www.ncbi.nlm.nih.gov/pubmed/23085451", "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "http://www.ncbi.nlm.nih.gov/pubmed/23568994", "http://www.ncbi.nlm.nih.gov/pubmed/23255116", "http://www.ncbi.nlm.nih.gov/pubmed/23663286", "http://www.ncbi.nlm.nih.gov/pubmed/22957288", "http://www.ncbi.nlm.nih.gov/pubmed/19923550", "http://www.ncbi.nlm.nih.gov/pubmed/24489866", "http://www.ncbi.nlm.nih.gov/pubmed/22305802", "http://www.ncbi.nlm.nih.gov/pubmed/20122289", "http://www.ncbi.nlm.nih.gov/pubmed/21501112" ], "ideal_answer": [ "Clinical trials have demonstrated that bapineuzumab, a humanized monoclonal antibody against the end terminus of amyloid plaques, is not effective for treatment of patients with Alzheimer's disease. The burden of beta amyloid plaques was reduced in response to bapineuzumab therapy. However, bapineuzumab therapy did not improve cognitive functioning and was associated with significant adverse effects in Alzheimer's disease patients." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "yesno", "id": "530cefaaad0bf1360c000004", "snippets": [ { "offsetInBeginSection": 517, "offsetInEndSection": 666, "text": " Thus far, results from two large phase 3 trial programs with bapineuzumab and solaneuzumab, respectively, have brought rather disappointing results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24216217", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 1043, "text": "More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23931438", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1137, "text": "Passive immunotherapy with monoclonal antibodies (mAbs) against A\u03b2 is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively, failed to meet their target of improving or stabilizing cognition and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23663286", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 607, "text": "The marginal effects observed in recent clinical studies of solanezumab, targeting monomeric A\u03b2, and bapineuzumab, targeting amyloid plaques, prompted expert comments that drug discovery efforts in Alzheimer's disease should focus on soluble forms of A\u03b2 rather than fibrillar A\u03b2 deposits found in amyloid plaques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582316", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 852, "text": "Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 990, "text": "Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23568994", "endSection": "abstract" }, { "offsetInBeginSection": 1790, "offsetInEndSection": 1904, "text": "Despite the alteration in biochemical composition, all 3 immunized subjects exhibited continued cognitive decline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Despite negative topline phase 3 clinical trial results for bapineuzumab and solanezumab in mild to moderate AD, findings from these trials and recent advances suggest renewed optimism for anti-amyloid therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23299380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "The lack of progress in the development of disease-modifying therapy in Alzheimer's disease (AD) was highlighted recently by the cessation of a phase 3 clinical trial studying the effects of bapineuzumab on mild to moderate disease. No treatment benefit was apparent, whereas several serious side effects occurred more commonly in the treatment group compared to placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085451", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 595, "text": "Clinical studies using the N-terminal-directed anti-A\u03b2 antibody bapineuzumab have demonstrated reduced brain PET-Pittsburg-B signals, suggesting the reduction of A\u03b2 plaques, and reduced levels of total and phosphorylated tau protein in the CSF of treated AD patients. Preclinical studies using 3D6 (the murine form of bapineuzumab) have demonstrated resolution of A\u03b2 plaque and vascular burdens, neuritic dystrophy, and preservation of synaptic density in the transgenic APP mouse models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357853", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1424, "text": "The clinical results of the initial studies with bapineuzumab were equivocal in terms of cognitive benefit. The occurrence of vasogenic edema after bapineuzumab, and more rarely brain microhemorrhages (especially in Apo E \u03b54 carriers), has raised concerns on the safety of these antibodies directed against the N-terminus of the A\u03b2 peptide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1330, "text": " The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-A\u03b2 monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce A\u03b2 burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21592055", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 523, "text": "However, the preliminary cognitive efficacy of bapineuzumab, a humanized anti-A\u03b2 monoclonal antibody, appears uncertain. Moreover, the occurrence of vasogenic edema and, more rarely, brain microhemorrhages, especially in apolipoprotein E \u03f54 carriers, have led to abandoning of the highest dose of the drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501112", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1118, "text": "However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent \u03b3-secretase inhibitor, raise the possibility that targeting A\u03b2 may not be clinically efficacious in AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501112", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 1209, "text": "The patient received four bapineuzumab infusions over a 39 week period. During the course of this treatment, there was no remarkable change in cognitive impairment as determined by MMSE scores. Forty-eight days after the fourth bapineuzumab infusion was given, MRI revealed that the patient had developed lacunar infarcts and possible vasogenic edema, probably related to immunotherapy, but a subsequent MRI scan 38 days later demonstrated resolution of vasogenic edema. The patient expired due to acute congestive heart failure complicated by progressive AD and cerebrovascular accident 378 days after the first bapineuzumab infusion and 107 days after the end of therapy. Neuropathological and biochemical analysis did not produce evidence of lasting plaque regression or clearance of A\u03b2 due to immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21263194", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1726, "text": "These results suggest that, in this particular case, bapineuzumab immunotherapy neither resulted in detectable clearance of amyloid plaques nor prevented further cognitive impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21263194", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1027, "text": "Bapineuzumab has been shown to reduce A\u03b2 burden in the brain of AD patients. However, its preliminary cognitive efficacy appears uncertain, particularly in ApoE \u03b54 carriers, and vasogenic edema may limit its clinical use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21091109", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1276, "text": "Bapineuzumab appears capable of reducing the cerebral beta-amyloid peptide burden in patients with Alzheimer's disease. However, particularly in APOE 4 carriers, its ability to slow disease progression remains uncertain, and vasogenic edema - a dose-limiting and potentially severe adverse reaction - may limit its clinical applicability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20497044", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 634, "text": "The first is a phase 2 study of passive immunotherapy with bapineuzumab, a humanized anti-Abeta monoclonal antibody directed against the N-terminus of Abeta. This trial showed no differences within dose cohorts on the primary efficacy analysis. Exploratory analyses showed potential treatment differences on cognitive and functional endpoints in study completers and apolipoprotein E epsilon4 noncarriers. A safety concern was the occurrence of reversible vasogenic edema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20388189", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 836, "text": "The first passive immunotherapy trial with bapineuzumab, a humanized monoclonal antibody against the end terminus of Abeta, also encountered some dose dependent adverse events during the Phase II portion of the study, vasogenic edema in 12 cases, which were significantly over represented in ApoE4 carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205639", "endSection": "abstract" } ] }, { "body": "Which deiodinase polymorphisms are implicated in arterial hypertension?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21415143", "http://www.ncbi.nlm.nih.gov/pubmed/17224473", "http://www.ncbi.nlm.nih.gov/pubmed/19178511", "http://www.ncbi.nlm.nih.gov/pubmed/18198294", "http://www.ncbi.nlm.nih.gov/pubmed/23329579", "http://www.ncbi.nlm.nih.gov/pubmed/19014646" ], "ideal_answer": [ "Two deiodinase polymorphisms are implicated in arterial hypertension: Ala92 type 2 deiodinase allele and rs7140952 polymorphism of DIO2", "At least two deiodinease polymorfisms are implicated in arterial hypertension:\nDIO 2 Thr92Ala\nrs7140952" ], "exact_answer": [ [ "rs7140952 polymorphism of DIO2", "rs7140952" ], [ "Ala92 type 2 deiodinase allele", "DIO 2 Thr92Ala" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10825", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006973", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110", "http://www.disease-ontology.org/api/metadata/DOID:10763", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007453" ], "type": "list", "id": "52ecf2dd98d023950500002e", "snippets": [ { "offsetInBeginSection": 1358, "offsetInEndSection": 1487, "text": "However, rs7140952 polymorphism is associated with components of metabolic syndrome including blood pressure and central obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23329579", "endSection": "abstract" }, { "offsetInBeginSection": 1106, "offsetInEndSection": 1245, "text": "Among euthyroid adults, the common Ala92 allele of the type 2 iodothyronine deiodinase increases risk for the development of hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17224473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Ala92 type 2 deiodinase allele increases risk for the development of hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17224473", "endSection": "title" }, { "offsetInBeginSection": 93, "offsetInEndSection": 280, "text": "This study investigates the clinical and biochemical response to L-T4 replacement therapy in hypothyroid patients in correlation with genetic variation in Deiodinase type || (DIO2) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23329579", "endSection": "abstract" } ] }, { "body": "At which kind of individuals is pharmacological treatment of subclinical hypothyroidism effective in reducing cardiovascular events?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23559085", "http://www.ncbi.nlm.nih.gov/pubmed/16542047", "http://www.ncbi.nlm.nih.gov/pubmed/17544610", "http://www.ncbi.nlm.nih.gov/pubmed/22529180", "http://www.ncbi.nlm.nih.gov/pubmed/16026106", "http://www.ncbi.nlm.nih.gov/pubmed/17636722", "http://www.ncbi.nlm.nih.gov/pubmed/19463607", "http://www.ncbi.nlm.nih.gov/pubmed/19114542" ], "ideal_answer": [ "Treatment of subclinical hypothyroidism is associated with fewer cardiovascular events in younger individuals, but this issue has not been resolved yet in elderly people." ], "exact_answer": [ "effective in younger individuals" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007037" ], "type": "factoid", "id": "52efbfccc8da898910000018", "snippets": [ { "offsetInBeginSection": 1447, "offsetInEndSection": 2119, "text": "sHT in older people should be not regarded as a unique condition, and moderately old patients (aged <70-75 y) could be considered clinically similar to the adult population, albeit with a higher optimal TSH target value. Conversely, the oldest old subjects should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. The decision to treat elderly people is still an unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559085", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1796, "text": "Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people. An appropriately powered randomized controlled trial of levothyroxine in SCH examining vascular outcomes is now warranted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22529180", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1709, "text": "SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463607", "endSection": "abstract" }, { "offsetInBeginSection": 1497, "offsetInEndSection": 1800, "text": "Sustained normalization of thyroid function during l-T(4) replacement therapy significantly decreases baPWV in female subclinical hypothyroid patients with autoimmune chronic thyroiditis, suggesting the improvement of arterial stiffening and, consequently, possible prevention of cardiovascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19114542", "endSection": "abstract" }, { "offsetInBeginSection": 1467, "offsetInEndSection": 1806, "text": "Our results suggest that L-T(4) replacement therapy may be especially beneficial in female subclinical hypothyroid patients with high baseline baPWV and pulse pressure. The beneficial effects of L-T(4) replacement therapy in decreasing arterial stiffening and thus preventing cardiovascular disease might be limited to this sub-population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17544610", "endSection": "abstract" }, { "offsetInBeginSection": 1695, "offsetInEndSection": 2027, "text": "Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16542047", "endSection": "abstract" }, { "offsetInBeginSection": 2028, "offsetInEndSection": 2165, "text": "However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16542047", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1633, "text": "Restoration of euthyroidism by levothyroxine (LT4) treatment may correct the lipid profile and cardiac abnormalities, especially in patients with an initially higher deviation from normality and higher serum TSH levels. Importantly, a strong association between SH and atherosclerotic cardiovascular disease, independent of the traditional risk factors, has been recently reported in a large cross-sectional survey (the Rotterdam Study). However, whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16026106", "endSection": "abstract" } ] }, { "body": "Is intense physical activity associated with longevity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23449779", "http://www.ncbi.nlm.nih.gov/pubmed/7707624", "http://www.ncbi.nlm.nih.gov/pubmed/22587716", "http://www.ncbi.nlm.nih.gov/pubmed/21618162", "http://www.ncbi.nlm.nih.gov/pubmed/2279154", "http://www.ncbi.nlm.nih.gov/pubmed/10670554" ], "ideal_answer": [ "YES:" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008136", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005082", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005081" ], "type": "yesno", "id": "518ccac0310faafe0800000b", "snippets": [ { "offsetInBeginSection": 1345, "offsetInEndSection": 1451, "text": "Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21618162", "endSection": "sections.0" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1690, "text": "Death rates declined with increased levels of total activity (estimated in kilocalories), and declined also with increased intensity of effort measured as from none, to light, to moderately vigorous or vigorous sports play. Death rates at any given quantity of physical exercise were lower for men playing moderately intense sports than for less vigorous men.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22587716", "endSection": "sections.0" }, { "offsetInBeginSection": 168, "offsetInEndSection": 318, "text": "he purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23449779", "endSection": "sections.0" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1230, "text": "This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23449779", "endSection": "sections.0" }, { "offsetInBeginSection": 470, "offsetInEndSection": 776, "text": "Light activities (<4 multiples of resting metabolic rate (METs)) were not associated with reduced mortality rates, moderate activities (4-<6 METs) appeared somewhat beneficial, and vigorous activities (> or =6 METs) clearly predicted lower mortality rates (p, trend = 0.72, 0.07, and <0.001, respectively).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10670554", "endSection": "sections.0" }, { "offsetInBeginSection": 1732, "offsetInEndSection": 1927, "text": "These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7707624", "endSection": "sections.0" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1042, "text": "The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2279154", "endSection": "sections.0" } ] }, { "body": "How homoplasy affects phylogenetic reconstruction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8042708", "http://www.ncbi.nlm.nih.gov/pubmed/21619604", "http://www.ncbi.nlm.nih.gov/pubmed/22728915", "http://www.ncbi.nlm.nih.gov/pubmed/15062799", "http://www.ncbi.nlm.nih.gov/pubmed/12116430", "http://www.ncbi.nlm.nih.gov/pubmed/22192390", "http://www.ncbi.nlm.nih.gov/pubmed/14530127", "http://www.ncbi.nlm.nih.gov/pubmed/22354957", "http://www.ncbi.nlm.nih.gov/pubmed/22491068", "http://www.ncbi.nlm.nih.gov/pubmed/9664695", "http://www.ncbi.nlm.nih.gov/pubmed/18577231", "http://www.ncbi.nlm.nih.gov/pubmed/18787123", "http://www.ncbi.nlm.nih.gov/pubmed/22228800", "http://www.ncbi.nlm.nih.gov/pubmed/15347815", "http://www.ncbi.nlm.nih.gov/pubmed/22431149", "http://www.ncbi.nlm.nih.gov/pubmed/20525577", "http://www.ncbi.nlm.nih.gov/pubmed/11098408", "http://www.ncbi.nlm.nih.gov/pubmed/16414286", "http://www.ncbi.nlm.nih.gov/pubmed/23906600", "http://www.ncbi.nlm.nih.gov/pubmed/11534998", "http://www.ncbi.nlm.nih.gov/pubmed/2682738", "http://www.ncbi.nlm.nih.gov/pubmed/10605118", "http://www.ncbi.nlm.nih.gov/pubmed/24932884", "http://www.ncbi.nlm.nih.gov/pubmed/23199982", "http://www.ncbi.nlm.nih.gov/pubmed/23378793", "http://www.ncbi.nlm.nih.gov/pubmed/15805007" ], "ideal_answer": [ "Evolutionary processes create both newly derived characteristics shared by related descendant lineages (homology) and \"false\" similarities which confound phylogenetic reconstruction (homoplasy). Homology arises by divergent evolution from a common ancestor and provides us with a phylogenetic signal, while homoplasy arises by convergent evolution or random coincidence. Homoplastic characters do not allows branch points and clade membership to be accurately estimated, as they may group unrelated taxa together. Such characters add \"noise\" in phylogenetic analysis and are not informative for the population genetics and the phylogenetic reconstruction of closely related taxa. In phylogenetic reconstruction, homoplasy leads to inaccurate conclusions about phylogenetic relationships among operational taxonomic units, and characters with high degree of homoplasy result in incongruences of cladistic relationships." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058974" ], "type": "summary", "id": "55476a3ff35db75526000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Phylogenetic reconstruction using molecular data is often subject to homoplasy, leading to inaccurate conclusions about phylogenetic relationships among operational taxonomic units.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15347815", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1634, "text": "Our use of nonhomoplastic whole-genome SNP characters allows branch points and clade membership to be estimated with great precision", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15347815", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1166, "text": "The control region proved to be a less useful molecular marker for the population genetics and the phylogenetic reconstruction of closely related taxa in A. urticae than it has for other species. The extreme bias in adenine and thymine content (A+T=90.91%) probably renders this region highly susceptible to homoplasy, resulting in a less informative molecular marker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15062799", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 751, "text": "Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22354957", "endSection": "abstract" }, { "offsetInBeginSection": 1659, "offsetInEndSection": 2014, "text": "These findings provide evidence for the occurrence of a high degree of homoplasy in the DR locus leading to convergent evolution to identical spoligotypes. The incongruence between Large Sequence Polymorphism and spoligotype polymorphism argues against the use of spoligotyping for establishing phylogenetic relationships within the Euro-American lineage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728915", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The species diversity of the phylum Rotifera has been largely studied on the basis of morphological characters. However, cladistic relationships within this group are poorly resolved due to extensive homoplasy in morphological traits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11098408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Molecular evolutionary processes modify DNA over time, creating both newly derived substitutions shared by related descendant lineages (phylogenetic signal) and \"false\" similarities which confound phylogenetic reconstruction (homoplasy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8042708", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 612, "text": "This added level of homoplasic \"noise\" can make DNA regions with repeats less reliable in phylogenetic reconstruction than those without repeats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8042708", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 751, "text": "Computational and phylogenetic analyses suggest that only some BH3 motifs arose by divergent evolution from a common ancestor (homology), whereas others arose by convergent evolution or random coincidence (homoplasy)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23199982", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 797, "text": "The high frequency of morphological homoplasy in pennatulaceans has led to many misinterpretations in the systematics of the group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23906600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "Conflict among data sources can be frequent in evolutionary biology, especially in cases where one character set poses limitations to resolution. Earthworm taxonomy, for example, remains a challenge because of the limited number of morphological characters taxonomically valuable. An explanation to this may be morphological convergence due to adaptation to a homogeneous habitat, resulting in high degrees of homoplasy. This sometimes impedes clear morphological diagnosis of species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378793", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1251, "text": "We also report one of the first findings of homoplasy in mitochondrial gene order, namely a shared relative position of trnV in unrelated isopod lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22491068", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 636, "text": "This taxon therefore provides the opportunity to evaluate those neural characters common to these two clades likely to be results of shared ancestry (homology) versus convergence (homoplasy). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431149", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 676, "text": "Taxa that experienced molecular homoplasy, recent selection, a spur of evolution, and so forth may disrupt the inference and cause incongruences in the estimated phylogeny.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22228800", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 972, "text": "myrmecophagy in these mammalian lineages was more likely because of homoplasy (convergent evolution) than being an ancestral character.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22192390", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1531, "text": "The four regions were equally affected by homoplasy and were, therefore, equally unreliable for phylogenetic reconstruction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Early hominid masticatory characters are widely considered to be more prone to homoplasy than characters from other regions of the early hominid skull and therefore less reliable for phylogenetic reconstruction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534998", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1457, "text": "These findings are in clear contrast with the views that rapidly evolving regions and the 3rd codon position have inevitable negative impact on phylogenetic reconstruction at deep historic level due to accumulation of multiple hits and subsequent elevation in homoplasy and saturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24932884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Phylogenetic reconstructions are often plagued by difficulties in distinguishing phylogenetic signal (due to shared ancestry) from phylogenetic noise or homoplasy (due to character-state convergences or reversals).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18787123", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1109, "text": "Homoplasy, in particular, is a difficulty faced by all methods of phylogenetic inference.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2682738", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1116, "text": "Homoplasy, in particular, is a difficulty faced by all methods of phylogenetic inference.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2682738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Sequence-based methods for phylogenetic reconstruction from (nucleic acid) sequence data are notoriously plagued by two effects: homoplasies and alignment errors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18577231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Early hominid masticatory characters are widely considered to be more prone to homoplasy than characters from other regions of the early hominid skull and therefore less reliable for phylogenetic reconstruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Molecular evolutionary processes modify DNA over time, creating both newly derived substitutions shared by related descendant lineages (phylogenetic signal) and \"false\" similarities which confound phylogenetic reconstruction (homoplasy)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8042708", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1538, "text": "The four regions were equally affected by homoplasy and were, therefore, equally unreliable for phylogenetic reconstruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534998", "endSection": "abstract" }, { "offsetInBeginSection": 1310, "offsetInEndSection": 1396, "text": "mellifera that the detection of size homoplasy may alter phylogenetic reconstructions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9664695", "endSection": "abstract" } ] }, { "body": "What is known about the association between the use of selective serotonin reuptake inhibitors during pregnancy and risk for autism in offspring?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24065914", "http://www.ncbi.nlm.nih.gov/pubmed/21727247", "http://www.ncbi.nlm.nih.gov/pubmed/23681158", "http://www.ncbi.nlm.nih.gov/pubmed/23604083", "http://www.ncbi.nlm.nih.gov/pubmed/20018455", "http://www.ncbi.nlm.nih.gov/pubmed/22090498", "http://www.ncbi.nlm.nih.gov/pubmed/23495208", "http://www.ncbi.nlm.nih.gov/pubmed/23042258" ], "ideal_answer": [ "Greater risk for autism spectrum disorders has been reported among mothers that have used selective serotonin reuptake inhibitors during pregnancy. However, others did not find an association between the use of selective serotonin reuptake inhibitors during pregnancy and risk for autism in offspring. Also, selective serotonin reuptake inhibitor use during pregnancy were associated with a greater number of gastrointestinal complaints in children with autism spectrum disorders." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007565", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017367", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321", "http://www.disease-ontology.org/api/metadata/DOID:12849", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247", "http://www.disease-ontology.org/api/metadata/DOID:0060041" ], "type": "summary", "id": "530cefaaad0bf1360c000009", "snippets": [ { "offsetInBeginSection": 709, "offsetInEndSection": 1188, "text": "In doing so, we examined whether two proposed risk factors - low birth weight (LBW), and in utero exposure to selective serotonin reuptake inhibitors (SSRIs) - are associated with greater behavioral homogeneity. Using data from the Western Australian Autism Biological Registry, this study found that LBW and maternal SSRI use during pregnancy were associated with greater sleep disturbances and a greater number of gastrointestinal complaints in children with ASD, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065914", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1173, "text": "The outcome of one study suggested that children with autism were more likely to have a mother who was prescribed an SSRI during pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681158", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1436, "text": "A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23604083", "endSection": "abstract" }, { "offsetInBeginSection": 1755, "offsetInEndSection": 1976, "text": "In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23604083", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 529, "text": "Repeated findings of elevated platelet serotonin levels in approximately one third of children with autism has led some to believe that dysfunctional serotonin signaling may be a causal mechanism for the disorder. Because serotonin is critical to fetal brain development, concerns have arisen regarding prenatal exposure to substances that manipulate serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23495208", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1209, "text": "Though the majority of studies conducted in infants and children suggest prenatal exposure to SSRIs does not affect neurodevelopment, interpretation must be tempered given small sample sizes. The only published study that focused on prenatal SSRI exposure and ASD found an increased risk with exposure to SSRIs, especially during the first trimester. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23495208", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 818, "text": "Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise. In the rodent model developed by Whitaker-Azmitia and colleagues, hyperserotonemia during fetal development results in a dysfunction of the hypothalamo-pituitary axis, affecting the amygdala as well as pro-social hormone oxytocin regulation. Dysfunction of the amygdala and abnormal oxytocin levels may underlie many clinical features of ASD. Selective serotonin reuptake inhibitors (SSRI) are the most widely used class of antidepressants drugs, and they are not contraindicated during pregnancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20018455", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1554, "text": "In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2 [95% confidence interval, 1.2-4.3]), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8 [95% confidence interval, 1.8-7.8]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21727247", "endSection": "abstract" }, { "offsetInBeginSection": 1732, "offsetInEndSection": 1963, "text": "Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21727247", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1697, "text": "Together, these results indicate that administration of SSRIs during a sensitive period of brain development results in long-lasting alterations in NE-LC circuit function in adults and may be useful in understanding the etiology of pervasive developmental disorders such as autism spectrum disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090498", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1295, "text": " Although several studies have not confirmed an increased risk for adverse neurodevelopment, a recent study observed an increased risk for autism spectrum disorders in prenatally exposed offspring. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23042258", "endSection": "abstract" }, { "offsetInBeginSection": 1600, "offsetInEndSection": 1776, "text": "Considering the important role of serotonin in central nervous system development, more studies are needed to assess the possible adverse effects on long-term neurodevelopment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23042258", "endSection": "abstract" } ] }, { "body": "Which transcription factors are involved in E-cadherin repression during EMT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19581928", "http://www.ncbi.nlm.nih.gov/pubmed/22833386", "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "http://www.ncbi.nlm.nih.gov/pubmed/22727060", "http://www.ncbi.nlm.nih.gov/pubmed/22562246", "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "http://www.ncbi.nlm.nih.gov/pubmed/22406531", "http://www.ncbi.nlm.nih.gov/pubmed/20735391", "http://www.ncbi.nlm.nih.gov/pubmed/22266854", "http://www.ncbi.nlm.nih.gov/pubmed/17615296", "http://www.ncbi.nlm.nih.gov/pubmed/18286686", "http://www.ncbi.nlm.nih.gov/pubmed/24297167" ], "ideal_answer": [ "Downregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression. Overexpression of Snail1 (Snail), Snail2 (Slug), Zeb1, Twist, SIP1 and DeltaEF1 have been found to mediate E-cadherin repression, induce the mesenchymal markers vimentin and fibronectin, and finally promote the migratory and invasive capabilities in cancer cells." ], "exact_answer": [ [ "Snail1 (Snail)" ], [ "Snail2 (Slug)" ], [ "Zeb1" ], [ "Twist" ], [ "SIP1" ], [ "DeltaEF1" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015820", "http://www.uniprot.org/uniprot/CADH1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058750", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060231" ], "type": "list", "id": "5319abe4b166e2b80600002e", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 117, "text": "ifferential role of Snail1 and Snail2 zinc fingers in E-cadherin repression and epithelial to mesenchymal transition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297167", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 363, "text": "nail1 (Snail) and Snail2 (Slug) are transcription factors that share a similar DNA binding structure of four and five C2H2 zinc finger motifs (ZF), respectively. Both factors bind specifically to a subset of E-box motifs (E2-box: CAGGTG/CACCTG) in target promoters like the E-cadherin promoter and are key mediators of epithelial-to-mesenchymal transition (EMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297167", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 167, "text": "hrombin induces slug-mediated E-cadherin transcriptional repression and the parallel up-regulation of N-cadherin by a transcription-independent mechanism in RPE cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22833386", "endSection": "title" }, { "offsetInBeginSection": 706, "offsetInEndSection": 848, "text": "We demonstrate, for the first time, that thrombin induces E-cadherin repression by stimulating snail-2 (SLUG) transcription factor expression,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22833386", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 543, "text": "Mutation of the putative GSK-3\u03b2 phosphorylation sites (S92/96A or S100/104A) enhanced the Slug/Snail2-mediated EMT properties of E-cadherin repression and vimentin induction, compared with wild-type Slug/Snail2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727060", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 162, "text": "xpression of E-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often lost due to promoter DNA methylation in basal-like breast cancer (BLBC),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562246", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 467, "text": "Here, we identified that Snail interacted with Suv39H1 (suppressor of variegation 3-9 homolog 1), a major methyltransferase responsible for H3K9me3 that intimately links to DNA methylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562246", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 809, "text": "We showed that Snail interacted with Suv39H1 and recruited it to the E-cadherin promoter for transcriptional repression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562246", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 984, "text": "Knockdown of Suv39H1 restored E-cadherin expression by blocking H3K9me3 and DNA methylation and resulted in the inhibition of cell migration, invasion and metastasis of BLBC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562246", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 104, "text": "9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406531", "endSection": "title" }, { "offsetInBeginSection": 806, "offsetInEndSection": 1014, "text": "Here, we have determined that methylation of histone H3 on lysine 9 (H3K9me2) is critical for promoter DNA methylation of E-cadherin in three TGF-\u03b2-induced EMT model cell lines, as well as in CLBC cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406531", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1206, "text": "Further, Snail interacted with G9a, a major euchromatin methyltransferase responsible for H3K9me2, and recruited G9a and DNA methyltransferases to the E-cadherin promoter for DNA methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406531", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1467, "text": "Knockdown of G9a restored E-cadherin expression by suppressing H3K9me2 and blocking DNA methylation. This resulted in inhibition of cell migration and invasion in vitro and suppression of tumor growth and lung colonization in in vivo models of CLBC metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406531", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 456, "text": "ZEB1, which targets E-cadherin repression, is a transcriptional regulator that has been implicated in EMT, and is associated with uterine and colorectal cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20735391", "endSection": "abstract" }, { "offsetInBeginSection": 2008, "offsetInEndSection": 2163, "text": "The introduction or knockdown of ZEB1 expression in bladder carcinoma cell lines showed enhanced or reduced migration and invasive potential, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20735391", "endSection": "abstract" }, { "offsetInBeginSection": 2504, "offsetInEndSection": 2672, "text": "However, in vitro assays showed enhanced or reduced migration and invasion after the introduction or reduction of ZEB1, respectively, in transfected bladder cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20735391", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1441, "text": "Finally, we showed aberrant IL-6 production and STAT3 activation in MCF-7 cells that constitutively express Twist, a metastatic regulator and direct transcriptional repressor of E-cadherin. To our knowledge, this is the first study that shows IL-6 as an inducer of an EMT phenotype in breast cancer cells and implicates its potential to promote breast cancer metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19581928", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 339, "text": "unctional loss of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration during embryonic development and tumour invasion. In most carcinomas, transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 438, "text": "Here, we report the identification of class I bHLH factor E2-2 (TCF4/ITF2) as a new EMT regulator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 772, "text": "E-cadherin repression mediated by E2-2 is indirect and independent of proximal E-boxes of the promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 888, "text": "Knockdown studies indicate that E2-2 expression is dispensable for maintenance of the EMT driven by Snail1 and E47.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1146, "text": "Slug mRNA was shown to be over-expressed in adenocarcinoma and inversely correlated to E-cadherin expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18286686", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1270, "text": "Overexpression of Slug in OE33 mediated E-cadherin repression and induced the mesenchymal markers vimentin and fibronectin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18286686", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 632, "text": "SIP1 and deltaEF1 each dramatically down-regulated the transcription of E-cadherin in NMuMG cells through direct binding to the E-cadherin promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17615296", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 770, "text": "Silencing of the expression of both SIP1 and deltaEF1, but not either alone, completely abolished TGF-beta-induced E-cadherin repression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17615296", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 112, "text": "eltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 143, "text": "ownregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 319, "text": "Using the EpFosER mammary tumour model we show that during EMT, upregulation of the transcriptional regulator deltaEF1 coincided with transcriptional repression of E-cadherin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 431, "text": "Ectopic expression of deltaEF1 in epithelial cells was sufficient to downregulate E-cadherin and to induce EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 577, "text": "Analysis of E-cadherin promoter activity and chromatin immunoprecipitation identified deltaEF1 as direct transcriptional repressor of E-cadherin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 729, "text": "In human cancer cells, transcript levels of deltaEF1 correlated directly with the extent of E-cadherin repression and loss of the epithelial phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1067, "text": "RNA interference-mediated downregulation of deltaEF1 in cancer cells was sufficient to derepress E-cadherin expression and restore cell to cell adhesion, suggesting that deltaEF1 is a key player in late stage carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1125, "text": "TGF-beta-induced the expression of Ets1, which in turn activated deltaEF1 promoter activity. Moreover, up-regulation of SIP1 and deltaEF1 expression by TGF-beta was suppressed by knockdown of Ets1 expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17615296", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 867, "text": "ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266854", "endSection": "abstract" } ] }, { "body": "Is desmin an intermediate filament protein involved in Dilated Cardiomyopathy (DCM)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24091796", "http://www.ncbi.nlm.nih.gov/pubmed/15475165", "http://www.ncbi.nlm.nih.gov/pubmed/16890305", "http://www.ncbi.nlm.nih.gov/pubmed/11515275", "http://www.ncbi.nlm.nih.gov/pubmed/14734054", "http://www.ncbi.nlm.nih.gov/pubmed/10974018", "http://www.ncbi.nlm.nih.gov/pubmed/17325244", "http://www.ncbi.nlm.nih.gov/pubmed/11374497", "http://www.ncbi.nlm.nih.gov/pubmed/7774871", "http://www.ncbi.nlm.nih.gov/pubmed/12025381", "http://www.ncbi.nlm.nih.gov/pubmed/15572040", "http://www.ncbi.nlm.nih.gov/pubmed/10904833", "http://www.ncbi.nlm.nih.gov/pubmed/15699919", "http://www.ncbi.nlm.nih.gov/pubmed/21525025" ], "ideal_answer": [ "According to the predominant view, desmin mutations cause dilated cardiomyopathy (DCM). Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Desmin defects were also recently identified in 1 familial dilated cardiomyopathy." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/DESM_HUMAN", "http://www.uniprot.org/uniprot/DESM_RAT", "http://www.uniprot.org/uniprot/DESM_CHICK", "http://www.uniprot.org/uniprot/DESM_MOUSE", "http://www.uniprot.org/uniprot/DESM_XENLA", "http://www.disease-ontology.org/api/metadata/DOID:12930", "http://www.uniprot.org/uniprot/DESM_CANFA", "http://www.uniprot.org/uniprot/DESM_PIG", "http://www.uniprot.org/uniprot/DESM_MESAU" ], "type": "yesno", "id": "55031963e9bde6963400002a", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 377, "text": "Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17325244", "endSection": "abstract" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1699, "text": "The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17325244", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 292, "text": "According to the predominant view, desmin mutations cause dilated cardiomyopathy (DCM). We evaluated a family with restrictive cardiomyopathy (RCM) associated with a novel desmin mutation and reviewed recent reports regarding the frequency of RCM in patients with desmin myopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16890305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 716, "text": "Dilated cardiomyopathy (DCM) is characterized by enlargement and dilation of all heart compartments associated with serious decrease of its contractile function. DCM hallmark is the combination of dystrophic and hypertrophic alterations of cardiomyocytes. Since the power output of cardiac cells is directly related to remodeling of their contractile machinery we investigated expression of selected contractile and cytoskeletal proteins in the left ventricle of DCM patients using immunoblotting. The content of the recognized protein markers of cardiomyocyte hypertrophy such as tubulin, desmin and slow skeletal myosin heavy chain isoform, MHCbeta, was significantly elevated in DCM compared to normal myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15699919", "endSection": "abstract" }, { "offsetInBeginSection": 1311, "offsetInEndSection": 1857, "text": "In contrast, overexpression of desmin filaments by itself is not detrimental to the heart. Although loss-of-function studies have been more limited, ablation of the desmin gene causes mitochondrial dysfunction and apoptosis, resulting in cardiomyopathy in mice. From function studies, abnormal desmin aggregation and disruption of the desmin networks resulting from expression of either mutant desmin or mutant CryAB have been shown to remodel the heart and compromise cardiac function, suggesting their synergistic roles in disease pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15572040", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 261, "text": "A missense mutation in the desmin gene (DES) causes DCM in a human family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15475165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 440, "text": "Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14734054", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 796, "text": "Familial DCM is commonly inherited as autosomal dominant trait; less frequently it is autosomal recessive, X-linked or matrilinear. The disease is clinically and genetically heterogeneous. Genes causally linked to this phenotype include dystrophin, dystrophin-associated glycoproteins, actin, desmin, beta-miosin heavy chain, cardiac troponin T, and mitochondrial DNA genes, mostly transfer RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12025381", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1309, "text": "Examination of families has identified so far eight disease genes, namely the dystrophin, tafazzin, cardiac actin, desmin, lamin A/C, delta- sarcoglycan, cardiac beta-myosin heavy chain, and cardiac troponin T gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11515275", "endSection": "abstract" }, { "offsetInBeginSection": 1789, "offsetInEndSection": 2001, "text": "Mutations of the desmin, delta-sarcoglycan, the cardiac actin and beta-myosin heavy chain as well as the troponin T gene are known to cause autosomal dominant-dilated cardiomyopathy without other abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11515275", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 605, "text": "Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11374497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two genes have been identified for the X-linked forms (dystrophin and tafazzin), whereas three other genes (actin, lamin A/C, and desmin) cause autosomal dominant DCM;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10974018", "endSection": "abstract" }, { "offsetInBeginSection": 1658, "offsetInEndSection": 1740, "text": "Desmin defects were also recently identified in 1 familial dilated cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10904833", "endSection": "abstract" }, { "offsetInBeginSection": 1904, "offsetInEndSection": 2043, "text": "By candidate gene screening, the molecular diagnosis can be provided for dystrophin, DAG, mitochondrial DNA, actin and desmin gene defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10904833", "endSection": "abstract" }, { "offsetInBeginSection": 1698, "offsetInEndSection": 1939, "text": "Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7774871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Desmin, the muscle-specific intermediate filament protein, is a major target in dilated cardiomyopathy and heart failure in humans and mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21525025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Desmin, the muscle-specific intermediate filament, is involved in myofibrillar myopathies, dilated cardiomyopathy and muscle wasting", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24091796", "endSection": "abstract" } ] }, { "body": "Is lambrolizumab effective for treatment of patients with melanoma ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23724846", "http://www.ncbi.nlm.nih.gov/pubmed/24416617", "http://www.ncbi.nlm.nih.gov/pubmed/23847357", "http://www.ncbi.nlm.nih.gov/pubmed/24089441", "http://www.ncbi.nlm.nih.gov/pubmed/24499550", "http://www.ncbi.nlm.nih.gov/pubmed/23970885", "http://www.ncbi.nlm.nih.gov/pubmed/24516336", "http://www.ncbi.nlm.nih.gov/pubmed/23907003", "http://www.ncbi.nlm.nih.gov/pubmed/24348481", "http://www.ncbi.nlm.nih.gov/pubmed/23997828" ], "ideal_answer": [ "Lambrolizumab, a programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibody, has been shown to be effective for treatment of patients with melanoma. High rate of sustained tumor regression with mainly minimal adverse effects in melanoma patients treated with lambrolizumab has been reported. Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year.", "Yes. In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018328", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018326", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545" ], "type": "yesno", "id": "530cefaaad0bf1360c000008", "snippets": [ { "offsetInBeginSection": 683, "offsetInEndSection": 1181, "text": "However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP-ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of molecularly targeted therapies, immunotherapies, and molecular targeted therapies with immunotherapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24089441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibodies have changed the landscape in oncology in 2013. The most mature results have been obtained in advanced melanoma patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Merck's lambrolizumab (MK-3475) monoclonal antibody received \"Breakthrough Therapy\" designation from the U.S. Food and Drug Administration in April for treating patients with advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23847357", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 263, "text": "The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724846", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1995, "text": "In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724846", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1031, "text": "Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907003", "endSection": "abstract" } ] }, { "body": "List human diseases involving genomic imprinting.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8565331", "http://www.ncbi.nlm.nih.gov/pubmed/15945483", "http://www.ncbi.nlm.nih.gov/pubmed/11568896", "http://www.ncbi.nlm.nih.gov/pubmed/12444886", "http://www.ncbi.nlm.nih.gov/pubmed/16035043", "http://www.ncbi.nlm.nih.gov/pubmed/7868070", "http://www.ncbi.nlm.nih.gov/pubmed/15802919", "http://www.ncbi.nlm.nih.gov/pubmed/22960339", "http://www.ncbi.nlm.nih.gov/pubmed/20822494", "http://www.ncbi.nlm.nih.gov/pubmed/12524013" ], "ideal_answer": [ "Prader Willi Syndrome\nAngelman syndrome\nBeckwith-Wiedemann syndrome\nHydatidiform mole\nCancer\nSilver-Russell syndrome\nDiabetes" ], "exact_answer": [ [ "Prader Willi Syndrome" ], [ "Angelman syndrome" ], [ "Beckwith-Wiedemann syndrome" ], [ "Hydatidiform mole" ], [ "Cancer" ], [ "Silver-Russell syndrome" ], [ "Diabetes" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000653", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018392", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071514", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ], "type": "list", "id": "54ff30dc6ad7dcbc1200000f", "snippets": [ { "offsetInBeginSection": 252, "offsetInEndSection": 371, "text": " Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS), a genomic imprinting disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960339", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 977, "text": "Perturbation of the allelic DNA methylation at ICRs is causally involved in several human diseases, including the Beckwith-Wiedemann and Silver-Russell syndromes, associated with aberrant foetal growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822494", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1114, "text": "Perturbed imprinted gene expression is also implicated in the neuro-developmental disorders Prader-Willi syndrome and Angelman syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822494", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 943, "text": "This epigenetic \"life cycle\" of imprinting (germline erasure, germline establishment, and somatic maintenance) can be disrupted in several human diseases, including Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), Angelman syndrome and Hydatidiform mole.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16035043", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1044, "text": "In the neurodevelopmental Rett syndrome, the way the ICR mediates imprinted expression is perturbed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16035043", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 455, "text": "eregulation of imprinted genes has been observed in a number of human diseases as gestation trophoblastic disease, Prader-Willi, Angelmann and Beckwith-Wiedemann syndromes and plays significant role in the carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15945483", "endSection": "abstract" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1077, "text": "Angelman's syndrome families, which are known to be imprinted. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Deregulation of imprinted genes has been observed in a number of human diseases such as Beckwith-Wiedemann syndrome, Prader-Willi/Angelman syndromes and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12524013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 438, "text": "Genomic imprinting is the phenomenon whereby some genes preferentially produce mRNA transcripts from the gene copy derived from the parent of a specific sex. It has been implicated in a number of human diseases (most of them of endocrine interest), such as Prader-Willi/Angelman syndromes, Silver-Russell syndrome, Beckwith-Wiedemann syndrome, transient neonatal diabetes, the focal form of nesidioblastosis, and pseudohypoparathyroidism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12444886", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 205, "text": "imprinting disorders like Beckwith-Wiedemann and Prader-Willi/Angelman syndromes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11568896", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 821, "text": "It is particularly interesting from the clinical point of view that a number of human diseases, such as the Beckwith-Wiedemann and Prader-Willi/Angelman syndromes, appear to involve unbalanced parental contributions of imprinted loci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7868070", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 769, "text": "Examples include the Prader-Willi, Angelman, and Beckwith-Wiedemann syndromes [Nicholls (1994): Am J Hum Genet 54:733-740], malignancy [Sapienza (1990): Biochim Biophys Acta 1072:51-61; Feinberg (1993): Nat Genet 4:110-113], and insulin-dependent diabetes mellitus (IDDM) [Julier et al. (1994) Nature 354:155-159; Bennett et al. (1995) Nat Genet 9:284-292]. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8565331", "endSection": "abstract" } ] }, { "body": "Why are insulators necessary in gene therapy vectors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21562592", "http://www.ncbi.nlm.nih.gov/pubmed/21205311", "http://www.ncbi.nlm.nih.gov/pubmed/21475904", "http://www.ncbi.nlm.nih.gov/pubmed/19352322", "http://www.ncbi.nlm.nih.gov/pubmed/12200360", "http://www.ncbi.nlm.nih.gov/pubmed/24098520", "http://www.ncbi.nlm.nih.gov/pubmed/9368350", "http://www.ncbi.nlm.nih.gov/pubmed/24312663", "http://www.ncbi.nlm.nih.gov/pubmed/19746166", "http://www.ncbi.nlm.nih.gov/pubmed/21247248", "http://www.ncbi.nlm.nih.gov/pubmed/14683449", "http://www.ncbi.nlm.nih.gov/pubmed/23786330", "http://www.ncbi.nlm.nih.gov/pubmed/15638709", "http://www.ncbi.nlm.nih.gov/pubmed/19536296" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11616828", "o": "GO:0043035" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1156211", "o": "http://linkedlifedata.com/resource/umls/label/A11616828" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11616828", "o": "chromatin insulator sequence binding" } ], "ideal_answer": [ "a) They inhibit oncogene activation upon vector integration and b) They maximize the probability of vector expression upon integration in heterochromatinic regions", "The presence of insulators in gene therapy vectors is necessary because these elements have the ability to help overcome the problem of position effects, caused due to random integration of the therapeutic genes in the host cell genome." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044009", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044008", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002273", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D038101", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006355", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043035", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010629", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005822", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016458", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015316", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010628", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045893", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045892", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010468", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009857", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004199", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015513" ], "type": "summary", "id": "52fa74252059c6d71c00005b", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 361, "text": "hromatin insulators separate active transcriptional domains and block the spread of heterochromatin in the genome. Studies on the chicken hypersensitive site-4 (cHS4) element, a prototypic insulator, have identified CTCF and USF-1/2 motifs in the proximal 250 bp of cHS4, termed the \"core\", which provide enhancer blocking activity and reduce position effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19746166", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 513, "text": "An attractive solution to the problem of oncogene activation is the inclusion of insulators/enhancer-blockers in the viral vectors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19536296", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 934, "text": "We propose the incorporation of chromatin insulators in the design of gene therapy vectors to overcome the problem of position effects. Chromatin insulators are protein-binding DNA elements that lack intrinsic promoter/enhancer activity but shelter genes from transcriptional influence of surrounding chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9368350", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1624, "text": "The design and incorporation of effective chromatin insulator sequences in the next generation of gene therapy vectors should lead to improved and more predictable expression of therapeutic transgenes and constitute an important step toward clinically effective gene therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9368350", "endSection": "abstract" } ] }, { "body": "Which deficiency is the cause of restless leg syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19935988", "http://www.ncbi.nlm.nih.gov/pubmed/11863398", "http://www.ncbi.nlm.nih.gov/pubmed/22258033", "http://www.ncbi.nlm.nih.gov/pubmed/21358851", "http://www.ncbi.nlm.nih.gov/pubmed/11310286", "http://www.ncbi.nlm.nih.gov/pubmed/11799409", "http://www.ncbi.nlm.nih.gov/pubmed/20814842", "http://www.ncbi.nlm.nih.gov/pubmed/19039990", "http://www.ncbi.nlm.nih.gov/pubmed/24267148", "http://www.ncbi.nlm.nih.gov/pubmed/20303704", "http://www.ncbi.nlm.nih.gov/pubmed/22096645", "http://www.ncbi.nlm.nih.gov/pubmed/17804903", "http://www.ncbi.nlm.nih.gov/pubmed/21211209", "http://www.ncbi.nlm.nih.gov/pubmed/14643912", "http://www.ncbi.nlm.nih.gov/pubmed/16982219", "http://www.ncbi.nlm.nih.gov/pubmed/18360657", "http://www.ncbi.nlm.nih.gov/pubmed/24101430", "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "http://www.ncbi.nlm.nih.gov/pubmed/12530992", "http://www.ncbi.nlm.nih.gov/pubmed/8363978", "http://www.ncbi.nlm.nih.gov/pubmed/21398376", "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "http://www.ncbi.nlm.nih.gov/pubmed/19467991", "http://www.ncbi.nlm.nih.gov/pubmed/22377249", "http://www.ncbi.nlm.nih.gov/pubmed/21779527", "http://www.ncbi.nlm.nih.gov/pubmed/23257652", "http://www.ncbi.nlm.nih.gov/pubmed/16828857", "http://www.ncbi.nlm.nih.gov/pubmed/20598107" ], "ideal_answer": [ "It has been well-documented that iron deficiency is the cause of restless leg syndrome. Magnesium and ferritin were also associated with restless leg syndrome." ], "exact_answer": [ "iron" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003677", "http://www.disease-ontology.org/api/metadata/DOID:0050425", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012148" ], "type": "factoid", "id": "530cefaaad0bf1360c000012", "snippets": [ { "offsetInBeginSection": 438, "offsetInEndSection": 775, "text": "We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1369, "text": "Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1562, "text": "These results when viewed along with prior RLS SPECT and autopsy studies of DAT, and cell culture studies with iron deficiency and DAT, suggest that membrane-bound striatal DAT, but not total cellular DAT, may be decreased in RLS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358851", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 860, "text": " Compared with the PD or healthy group, the level of serum ferritin and the H-reflex latency of tibial nerve were significantly decreased in PD with RLS group (P < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211209", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1031, "text": "Deficiency of iron and decreased inhibition function of spinal cord may lead to the occurrence of RLS in PD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211209", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 691, "text": "Association of iron deficiency with febrile seizures, pica, breath holding spells, restless leg syndrome and thrombosis is increasingly being recognized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20814842", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 857, "text": " Iron status was generally poor among regular blood donors, especially in women, with a high incidence of iron depletion (>20%) and RLS (18%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598107", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1350, "text": "Iron status is poor in regular blood donors, restless legs syndrome is common, and the routine iron supplementation is insufficient. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598107", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1366, "text": "Furthermore, there appears to be an association between iron deficiency and those suffering from Restless Leg Syndrome (RLS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19935988", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1784, "text": "The authors propose that PPIs, such as omeprazole, may interfere with iron absorption in certain patients and that a subpopulation of patients who develop significant iron deficiency characterized by low serum ferritin levels while on PPIs may also develop RLS-like symptoms (including RLSAP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19935988", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 211, "text": "Clinical studies have implicated the dopaminergic system in RLS, while others have suggested that it is associated with insufficient levels of brain iron. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19467991", "endSection": "abstract" }, { "offsetInBeginSection": 1674, "offsetInEndSection": 1877, "text": "The results are consistent with the hypothesis that a primary iron insufficiency produces a dopaminergic abnormality characterized as an overly activated dopaminergic system as part of the RLS pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19467991", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 608, "text": "RLS may also be secondary to a number of conditions including iron deficiency, pregnancy and end-stage renal failure and, perhaps, neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18360657", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 860, "text": "The pathogenesis of RLS probably involves the interplay of systemic or brain iron deficiency and impaired dopaminergic neurotransmission in the subcortex of the brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18360657", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 958, "text": "All patients showed low levels of ferritin and iron supplementation was effective in five cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19039990", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 724, "text": "Clinical and animal studies that support the benefits of iron supplementation, independent of increasing hemoglobin, such as those on immune function, physical performance, thermoregulation, cognition, and restless leg syndrome and aluminum absorption is the subject of this narrative review.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17804903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "Restless leg syndrome (RLS) and periodic limb movement disorder (PLMD) are considered to be a continuum of a neurological sleep disorder associated with abnormal iron metabolism or deficiency. I describe a case of RLS and PLMD in a cystic fibrosis patient with iron deficiency from chronic hemoptysis. This is the first case that reports RLS and PLMD manifesting from iron deficiency caused by chronic hemoptysis in advanced cystic fibrosis lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Restless leg syndrome manifested by iron deficiency from chronic hemoptysis in cystic fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982219", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Diurnal effects on motor control are evident in the human disease of Restless Leg Syndrome (RLS), which is purported to be linked to brain iron deficiency as well as alterations in dopaminergic systems. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16828857", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 974, "text": "Iron deficiency in the central nervous system is known to cause motor impairment and cognitive deficits; more recently, it has been suggested that it may play a role in the pathophysiology of the restless leg syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12530992", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 412, "text": "Restless leg syndrome (RLS), aging, pregnancy, uraemia, iron deficiency, polyneuropathy are some of the common causes of secondary PLMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11799409", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 662, "text": "The syndrome is increasingly often diagnosed, particularly in association with iron deficiency, during pregnancy, in chronic renal failure and in patients with peripheral neuropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11310286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8363978", "endSection": "title" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1373, "text": "A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "endSection": "abstract" } ] }, { "body": "What histone modification is recognized by the bromodomain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15014446", "http://www.ncbi.nlm.nih.gov/pubmed/21596426", "http://www.ncbi.nlm.nih.gov/pubmed/17049045", "http://www.ncbi.nlm.nih.gov/pubmed/21189220", "http://www.ncbi.nlm.nih.gov/pubmed/10746732", "http://www.ncbi.nlm.nih.gov/pubmed/23095041", "http://www.ncbi.nlm.nih.gov/pubmed/15382140", "http://www.ncbi.nlm.nih.gov/pubmed/15143168", "http://www.ncbi.nlm.nih.gov/pubmed/21851057", "http://www.ncbi.nlm.nih.gov/pubmed/15970672", "http://www.ncbi.nlm.nih.gov/pubmed/16265664", "http://www.ncbi.nlm.nih.gov/pubmed/21271695", "http://www.ncbi.nlm.nih.gov/pubmed/10716917" ], "ideal_answer": [ "Acetylated lysines in histones (generally H3 and H4)" ], "exact_answer": [ "Acetylated lysines" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016573", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016570" ], "type": "factoid", "id": "53398855d6d3ac6a3400005b", "snippets": [ { "offsetInBeginSection": 280, "offsetInEndSection": 361, "text": "acetyllysine-specific protein-protein interaction with bromodomain reader modules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095041", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 228, "text": "Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21851057", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 472, "text": " three acetyllysine ligands are indentified for a PHD-adjacent bromodomain in BPTF via systematic screening and biophysical characterization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596426", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 712, "text": "acetyl-lysine binding bromodomain (BRD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21271695", "endSection": "abstract" }, { "offsetInBeginSection": 7, "offsetInEndSection": 66, "text": "bromodomain proteins bind to acetylated lysines in histones", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21189220", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 251, "text": "romodomains are present in many chromatin-associated proteins such as the SWI/SNF and RSC chromatin remodelling and the SAGA HAT (histone acetyltransferase) complexes, and can bind to acetylated lysine residues in the N-terminal tails of the histones", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17049045", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 60, "text": "recognition of acetylated histones by bromodomains", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17049045", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 160, "text": "BRD7, a novel bromodomain gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16265664", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 717, "text": "BRD7 interacted with H3 peptide acetylated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16265664", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 424, "text": "bromodomain-containing proteins that recognize histone acetylation sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15970672", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 677, "text": "bromodomains of Gcn5, PCAF, TAF1 and CBP are able to recognize acetyllysine residues in histones", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15382140", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 26, "text": "romodomain factor 1 (Bdf1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15143168", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 274, "text": " Bdf1 binds preferentially to acetylated histone H4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15143168", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 233, "text": "chromatin remodeling complex RSC bears multiple bromodomains, motifs for acetyl-lysine and histone tail interaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15014446", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 769, "text": " in vitro binding of a HAT bromodomain with acetylated lysines within H3 and H4 amino-terminal peptides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10746732", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 583, "text": "bromodomain, that recognizes acetylated residues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10716917", "endSection": "abstract" } ] }, { "body": "What memory problems are reported in the \" Gulf war syndrome\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15251045", "http://www.ncbi.nlm.nih.gov/pubmed/11600803", "http://www.ncbi.nlm.nih.gov/pubmed/14590665", "http://www.ncbi.nlm.nih.gov/pubmed/12446953", "http://www.ncbi.nlm.nih.gov/pubmed/9005271", "http://www.ncbi.nlm.nih.gov/pubmed/14515407", "http://www.ncbi.nlm.nih.gov/pubmed/9096828", "http://www.ncbi.nlm.nih.gov/pubmed/11478226", "http://www.ncbi.nlm.nih.gov/pubmed/21930452" ], "ideal_answer": [ "Loss of memory and dysmnesia are memory problems reported in the \" Gulf war syndrome\". Patients suffering from this syndrome often have other\nnonspecific symptoms such as fatigue, skin rash, headache, muscle and joint pain and sexual dysfunction." ], "exact_answer": [ [ "loss of memory" ], [ "dysmnesia" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008568", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008569", "http://www.disease-ontology.org/api/metadata/DOID:4491", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018923", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007613" ], "type": "list", "id": "530cefaaad0bf1360c000011", "snippets": [ { "offsetInBeginSection": 1233, "offsetInEndSection": 1501, "text": "The strongest associations were for mood swings (OR 20.9, 95%CI 16.2-27.0), memory loss/lack of concentration (OR 19.6, 95% CI 15.5-24.8), night sweats (OR 9.9, 95% CI 6.5-15.2), general fatigue (OR 9.6, 95% CI 8.3-11.1) and sexual dysfunction (OR 4.6, 95%CI 3.2-6.6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15251045", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 1017, "text": "The symptoms include incapacitating fatigue, musculoskeletel and joint pains, headaches, neuropsychiatric disorders, affect changes, confusion, visual problems, changes of gait, loss of memory, lymphadenopathies, respiratory impairment, impotence, and urinary tract morphological and functional alterations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14515407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "In early 1992, U.S. troops returning from the Gulf War began reporting a variety of nonspecific symptoms such as fatigue, skin rash, headache, muscle and joint pain, and loss of memory. These reports marked the beginning of what was to be identified as the Gulf War Syndrome (GWS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11600803", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 561, "text": "We report on a 29-year-old man who suffered from dysmnesia, disturbance of orientation, cognitive impairment, and double vision. His history revealed several front-line operations in 1990 and 1991 during the Gulf War. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11478226", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1059, "text": "Neuropsychological tests disclosed severe cognitive impairment especially concerning memory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11478226", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1308, "text": "A cluster of common health problems included: skin rash, cough, depression, unintentional weight loss, insomnia, and memory problems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9096828", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1677, "text": "Syndromes 1 (\"impaired cognition,\" characterized by problems with attention, memory, and reasoning, as well as insomnia, depression, daytime sleepiness, and headaches), 2 (\"confusion-ataxia,\" characterized by problems with thinking, disorientation, balance disturbances, vertigo, and impotence), and 3 (\"arthro-myo-neuropathy,\" characterized by joint and muscle pains, muscle fatigue, difficulty lifting, and extremity paresthesias) represented strongly clustered symptoms; whereas, syndromes 4 (\"phobia-apraxia\"), 5 (\"fever-adenopathy\"), and 6 (\"weakness-incontinence\") involved weaker clustering and mostly overlapped syndromes 2 and 3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9005271", "endSection": "abstract" } ] }, { "body": "Is cadasil syndrome a hereditary disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23355563", "http://www.ncbi.nlm.nih.gov/pubmed/23587639", "http://www.ncbi.nlm.nih.gov/pubmed/21772710", "http://www.ncbi.nlm.nih.gov/pubmed/23221354", "http://www.ncbi.nlm.nih.gov/pubmed/23394849", "http://www.ncbi.nlm.nih.gov/pubmed/23597439", "http://www.ncbi.nlm.nih.gov/pubmed/21197470", "http://www.ncbi.nlm.nih.gov/pubmed/24274803", "http://www.ncbi.nlm.nih.gov/pubmed/23465844", "http://www.ncbi.nlm.nih.gov/pubmed/23868154", "http://www.ncbi.nlm.nih.gov/pubmed/23602593", "http://www.ncbi.nlm.nih.gov/pubmed/23412372", "http://www.ncbi.nlm.nih.gov/pubmed/23799017", "http://www.ncbi.nlm.nih.gov/pubmed/23649698", "http://www.ncbi.nlm.nih.gov/pubmed/23308019", "http://www.ncbi.nlm.nih.gov/pubmed/23799141", "http://www.ncbi.nlm.nih.gov/pubmed/23460375", "http://www.ncbi.nlm.nih.gov/pubmed/23705041", "http://www.ncbi.nlm.nih.gov/pubmed/23832984", "http://www.ncbi.nlm.nih.gov/pubmed/23639391", "http://www.ncbi.nlm.nih.gov/pubmed/23584202" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "UMLS_CUI:C0751587" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "cadasil" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "C499374" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "Notch homolog 3 (Drosophila) protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "NOTCH3 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400718" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400738" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "CADASIL protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "MSH2010_2010_02_22:D046589" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "MeSH" } ], "ideal_answer": [ "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. CADASIL is the most common form of hereditary cerebral angiopathy." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046589", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020271", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030342", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.disease-ontology.org/api/metadata/DOID:13945" ], "type": "yesno", "id": "532361fd9b2d7acc7e000013", "snippets": [ { "offsetInBeginSection": 23, "offsetInEndSection": 487, "text": " CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868154", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 158, "text": " (CADASIL) is the most common form of hereditary cerebral angiopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23705041", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 386, "text": "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23639391", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 233, "text": "Mutations in the TREX1 and NOTCH3 genes cause retinal vasculopathy with cerebral leukodystrophy (RVCL) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23602593", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 569, "text": "We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23584202", "endSection": "abstract" } ] }, { "body": "Which neuroendocrine tumors are associated with specific tumor syndromes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23010473", "http://www.ncbi.nlm.nih.gov/pubmed/21181474", "http://www.ncbi.nlm.nih.gov/pubmed/19708762", "http://www.ncbi.nlm.nih.gov/pubmed/22041710", "http://www.ncbi.nlm.nih.gov/pubmed/14685672" ], "ideal_answer": [ "Neuroendocrine tumors are a heterogeneous group of benign and malignant neoplasias, detectable in the context of hereditary tumor syndromes in up to 30% of cases. Neuroendocrine tumors include medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma." ], "exact_answer": [ [ "medullary thyroid carcinoma" ], [ "gastroenteropancreatic tumors" ], [ "pheochromocytoma" ], [ "paraganglioma" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:169" ], "type": "list", "id": "55031628e9bde69634000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Pheochromocytomas are neuroendocrine tumors of the adrenal medulla which can occur either sporadically or in the context of hereditary tumor syndromes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23010473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22041710", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 184, "text": "Pancreatic neuroendocrine tumors (PNETs) are a characteristic feature of the tumor syndromes multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21181474", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1804, "text": "This review focuses on hereditary syndromes with neuroendocrine tumors, including multiple endocrine neoplasia types 1 and 2, Von Hippel-Lindau disease, neurofibromatosis type 1, Carney complex, pheochromocytoma-paraganglioma syndrome, and familial nonmedullary thyroid carcinoma. In addition, several individual neuroendocrine tumors are described, such as medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma, emphasizing specific histopathologic characteristics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19708762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Neuroendocrine tumors (NETs) are a heterogeneous group of benign and malignant neoplasias, detectable in the context of hereditary tumor syndromes in up to 30% of cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685672", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1218, "text": "RET gene analysis can identify individuals with a very high risk to develop familial medullary cancer (MEN2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685672", "endSection": "abstract" }, { "offsetInBeginSection": 1577, "offsetInEndSection": 1803, "text": "In addition, several individual neuroendocrine tumors are described, such as medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma, emphasizing specific histopathologic characteristics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19708762", "endSection": "abstract" } ] }, { "body": "How many periods of regulatory innovation led to the evolution of vertebrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21852499" ], "ideal_answer": [ "Investigators proposed that there have been three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers." ], "exact_answer": [ "Three" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014714", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005075" ], "type": "factoid", "id": "56d1da3b67f0cb3d66000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Three periods of regulatory innovation during vertebrate evolution.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "title" }, { "offsetInBeginSection": 141, "offsetInEndSection": 927, "text": "To investigate the gain of regulatory elements throughout vertebrate evolution, we identified genome-wide sets of putative regulatory regions for five vertebrates, including humans. These putative regulatory regions are conserved nonexonic elements (CNEEs), which are evolutionarily conserved yet do not overlap any coding or noncoding mature transcript. We then inferred the branch on which each CNEE came under selective constraint. Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1180, "text": "Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 669, "text": "Our analysis identified three extended periods in the evolution of gene regulatory elements. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 927, "text": "Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 928, "text": "Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 669, "text": "We then inferred the branch on which each CNEE came under selective constraint. Our analysis identified three extended periods in the evolution of gene regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 669, "text": "Our analysis identified three extended periods in the evolution of gene regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" }, { "offsetInBeginSection": 670, "offsetInEndSection": 928, "text": "Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract" } ] }, { "body": "Is nintedanib effective for Idiopathic Pulmonary Fibrosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25628503", "http://www.ncbi.nlm.nih.gov/pubmed/24834811", "http://www.ncbi.nlm.nih.gov/pubmed/26039104", "http://www.ncbi.nlm.nih.gov/pubmed/25439569", "http://www.ncbi.nlm.nih.gov/pubmed/24782550", "http://www.ncbi.nlm.nih.gov/pubmed/26380465", "http://www.ncbi.nlm.nih.gov/pubmed/24556663", "http://www.ncbi.nlm.nih.gov/pubmed/23818761", "http://www.ncbi.nlm.nih.gov/pubmed/26261848", "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "http://www.ncbi.nlm.nih.gov/pubmed/25767391", "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "http://www.ncbi.nlm.nih.gov/pubmed/25635490" ], "ideal_answer": [ "Yes, nintedanib is approved for Idiopathic Pulmonary Fibrosis treatment. Nintedanib was shown to slow the decline in lung function, decrease acute exacerbations, decrease the annual rate of decline in forced vital capacity and increase time to acute exacerbation." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054990", "http://www.disease-ontology.org/api/metadata/DOID:0050156" ], "type": "yesno", "id": "56c048e2ef6e39474100001d", "snippets": [ { "offsetInBeginSection": 532, "offsetInEndSection": 689, "text": "In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26380465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "endSection": "title" }, { "offsetInBeginSection": 629, "offsetInEndSection": 1217, "text": " In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1372, "text": " Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26039104", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 558, "text": "Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261848", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1217, "text": "Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25767391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628503", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 628, "text": " More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 630, "text": "Nintedanib (Ofev(\u00ae)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1037, "text": "This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24782550", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24834811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818761", "endSection": "title" }, { "offsetInBeginSection": 2247, "offsetInEndSection": 2383, "text": "These results suggest that nintedanib may impact the progressive course of fibrotic lung diseases such as idiopathic pulmonary fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24556663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25439569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The tyrosine kinase inhibitor nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24556663", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 470, "text": "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 304, "text": "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 436, "text": "Data from the Phase II TOMORROW study suggested that nintedanib 150\ufffdmg twice daily had clinical benefits with an acceptable safety profile.METHODS: The INPULSIS\ufffd trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150\ufffdmg twice daily with placebo in patients with IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24834811", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 297, "text": "Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "endSection": "abstract" }, { "offsetInBeginSection": 1615, "offsetInEndSection": 2143, "text": "The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 563, "text": "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Nintedanib (Ofev(\ufffd)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "endSection": "title" }, { "offsetInBeginSection": 112, "offsetInEndSection": 542, "text": "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "endSection": "abstract" } ] }, { "body": "What is the role of SERCA in diabetic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18570267", "http://www.ncbi.nlm.nih.gov/pubmed/16810072", "http://www.ncbi.nlm.nih.gov/pubmed/22137362", "http://www.ncbi.nlm.nih.gov/pubmed/20008278", "http://www.ncbi.nlm.nih.gov/pubmed/22621761", "http://www.ncbi.nlm.nih.gov/pubmed/12217882", "http://www.ncbi.nlm.nih.gov/pubmed/19882101", "http://www.ncbi.nlm.nih.gov/pubmed/12206992", "http://www.ncbi.nlm.nih.gov/pubmed/21441944", "http://www.ncbi.nlm.nih.gov/pubmed/17716638", "http://www.ncbi.nlm.nih.gov/pubmed/18492789", "http://www.ncbi.nlm.nih.gov/pubmed/22590623" ], "ideal_answer": [ "Diabetic cardiomyopathy is accompanied by reduced SERCA levels and activity in later stages. The up-regulation of SERCA2a in the early phase of type 2 diabetes is an important physiological adaptation of the heart." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.disease-ontology.org/api/metadata/DOID:9351" ], "type": "summary", "id": "51713cb58ed59a060a000006", "snippets": [ { "offsetInBeginSection": 919, "offsetInEndSection": 1115, "text": "Compared with control group, [Ca(2+)](i) and the expression of CaSR, RyR and SERCA/PLN were decreased, while PKC-\u03b1 and PLN were significantly increased in a time-dependent manner in diabetic group", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137362", "endSection": "sections.0" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1492, "text": "Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19882101", "endSection": "sections.0" }, { "offsetInBeginSection": 689, "offsetInEndSection": 888, "text": "Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17716638", "endSection": "sections.0" }, { "offsetInBeginSection": 1538, "offsetInEndSection": 1651, "text": "The levels of SERCA and GLUT4, but not PLB, were significantly reduced in diabetic hearts compared with controls.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12217882", "endSection": "sections.0" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1518, "text": "CONCLUSIONS: CASQ2, FKBP12.6 and SERCA2a were down-regulated in diabetic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21441944", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Reduced sarcoplasmic calcium ATPase (SERCA2a) expression has been shown to play a significant role in the cardiac dysfunction in diabetic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20008278", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Depressed sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) and Ca(2+)-release channels (ryanodine receptor RyR2) are involved in diabetic cardiomyopathy, however, the implication of intracellular calcium handling proteins in SR is undefined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18570267", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The depressed sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) and Ca2+-release channels (ryanodine receptor RyR2) are involved in the diabetic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16810072", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to diminished expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase SERCA2a.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12206992", "endSection": "sections.0" } ] }, { "body": "Is pesticide exposure associated with polyneuropathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2158793", "http://www.ncbi.nlm.nih.gov/pubmed/23251840", "http://www.ncbi.nlm.nih.gov/pubmed/23251841", "http://www.ncbi.nlm.nih.gov/pubmed/16140621", "http://www.ncbi.nlm.nih.gov/pubmed/21432383", "http://www.ncbi.nlm.nih.gov/pubmed/19079407", "http://www.ncbi.nlm.nih.gov/pubmed/22728724", "http://www.ncbi.nlm.nih.gov/pubmed/23185328", "http://www.ncbi.nlm.nih.gov/pubmed/21787602", "http://www.ncbi.nlm.nih.gov/pubmed/12718377", "http://www.ncbi.nlm.nih.gov/pubmed/7998771", "http://www.ncbi.nlm.nih.gov/pubmed/15116371", "http://www.ncbi.nlm.nih.gov/pubmed/17107865", "http://www.ncbi.nlm.nih.gov/pubmed/11600725", "http://www.ncbi.nlm.nih.gov/pubmed/7194975", "http://www.ncbi.nlm.nih.gov/pubmed/10528323", "http://www.ncbi.nlm.nih.gov/pubmed/21258583", "http://www.ncbi.nlm.nih.gov/pubmed/9311548", "http://www.ncbi.nlm.nih.gov/pubmed/14691285", "http://www.ncbi.nlm.nih.gov/pubmed/16856766", "http://www.ncbi.nlm.nih.gov/pubmed/16042503", "http://www.ncbi.nlm.nih.gov/pubmed/16702122", "http://www.ncbi.nlm.nih.gov/pubmed/19922373", "http://www.ncbi.nlm.nih.gov/pubmed/7787373", "http://www.ncbi.nlm.nih.gov/pubmed/11843436", "http://www.ncbi.nlm.nih.gov/pubmed/21601587", "http://www.ncbi.nlm.nih.gov/pubmed/22399093", "http://www.ncbi.nlm.nih.gov/pubmed/23703814", "http://www.ncbi.nlm.nih.gov/pubmed/22262687", "http://www.ncbi.nlm.nih.gov/pubmed/1481520", "http://www.ncbi.nlm.nih.gov/pubmed/8160653", "http://www.ncbi.nlm.nih.gov/pubmed/11146591", "http://www.ncbi.nlm.nih.gov/pubmed/6179111", "http://www.ncbi.nlm.nih.gov/pubmed/9592856", "http://www.ncbi.nlm.nih.gov/pubmed/11045057", "http://www.ncbi.nlm.nih.gov/pubmed/22655091", "http://www.ncbi.nlm.nih.gov/pubmed/2707289", "http://www.ncbi.nlm.nih.gov/pubmed/2462700", "http://www.ncbi.nlm.nih.gov/pubmed/18780003", "http://www.ncbi.nlm.nih.gov/pubmed/21120082", "http://www.ncbi.nlm.nih.gov/pubmed/1665780" ], "ideal_answer": [ "Yes, it is associated with peripheral neuropathy.", "Yes, pesticide exposure is associated with delayed polyneuropathy. Electrophysiological studies have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). Pesticide exposure was also implicated in Alzheimer's disease, suicide attempts and affective disorders." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011115", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004781", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016273", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010575" ], "type": "yesno", "id": "530cefaaad0bf1360c000010", "snippets": [ { "offsetInBeginSection": 262, "offsetInEndSection": 431, "text": "As the syndrome occurred after the acute cholinergic syndrome but before organophosphate-induced delayed polyneuropathy, the syndrome was called 'intermediate syndrome'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16856766", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 1204, "text": "The characteristic features of the IMS are weakness of the muscles of respiration (diaphragm, intercostal muscles and accessory muscles including neck muscles) and of proximal limb muscles. Accompanying features often include weakness of muscles innervated by some cranial nerves. It is now emerging that the degree and extent of muscle weakness may vary following the onset of the IMS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16856766", "endSection": "abstract" }, { "offsetInBeginSection": 3353, "offsetInEndSection": 3805, "text": "Electrophysiological studies following OP poisoning have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16856766", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 387, "text": "Organophosphate-induced delayed polyneuropathy is a sensory-motor distal axonopathy which usually occurs after exposure of certain OP insecticides. Neuropathies due to ingestion of OPs have rarely been reported in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780003", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 830, "text": "We report a patient with serious organophosphorus-induced delayed neuropathy due to malathion injection. The patient was a 32-year-old female who self-injected undetermined amounts of malathion over the median nerve trace on the forearm crease in a suicide attempt which resulted in peripheral neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780003", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 845, "text": " Acutely, these patients present with cholinergic crisis; intermediate syndrome and delayed polyneuropathy are other sequel of this form of poisoning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19079407", "endSection": "abstract" }, { "offsetInBeginSection": 1667, "offsetInEndSection": 1803, "text": "There was no strong evidence of irreversible peripheral nerve damage following acute OP poisoning, however further studies are required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185328", "endSection": "abstract" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1613, "text": "Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728724", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1453, "text": "The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21601587", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 357, "text": "These compounds cause four important neurotoxic effects in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP) and chronic organophosphate-induced neuropsychiatric disorder (COPIND). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21787602", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 819, "text": "An 18-year-old woman and a 22-year-old man were admitted to the hospital with weakness, paresthesia, and gait disturbances at 35 and 22 days, respectively, after ingesting dimethyl-2,2-dichloro vinyl phosphate (DDVP). Neurological examination revealed weakness, vibration sense loss, bilateral dropped foot, brisk deep tendon reflexes, and bilaterally positive Babinski sign. Electroneurography demonstrated distal motor polyneuropathy with segmental demyelination associated with axonal degeneration prominent in the distal parts of both lower extremities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19922373", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 912, "text": "Sensory complaints and electrodiagnostic findings consistent with polyneuropathy were found in a minority (3/7) of subjects 28 years after an acute toxic arsenic exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Organophosphate-induced delayed polyneuropathy (OPIDP) is a rare toxicity resulting from exposure to certain organophosphorus (OP) esters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16042503", "endSection": "abstract" }, { "offsetInBeginSection": 1800, "offsetInEndSection": 1914, "text": "Therefore, OPIDP may develop only after very large exposures to insecticides, causing severe cholinergic toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16042503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15116371", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1478, "text": "We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15116371", "endSection": "abstract" }, { "offsetInBeginSection": 1498, "offsetInEndSection": 1790, "text": "Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14691285", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 284, "text": "Besides the well known acute cholinergic toxicity, these compounds may cause late-onset distal polyneuropathy occurring two to three weeks after the acute exposure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12718377", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 730, "text": "Electromyography demonstrated motor weighed sensory-motor polyneuropathy with axonal degeneration significant in the distal parts of bilateral lower extremities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12718377", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1055, "text": "The two cases are presented here since organophosphate poisonings are common in our country, and since late-onset polyneuropathy is not a well known clinical presentation as acute toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12718377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The course of organophosphate-induced delayed polyneuropathy (OPIDP) in humans has not been quantitatively measured in epidemiologic studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11843436", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1443, "text": "The persistence of deficits in motor strength in all severely poisoned patients regardless of pesticide type was unexpected, and may reflect persistent cholinergic blockade or intermediate syndrome, neuropathy, or a combination of these.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11843436", "endSection": "abstract" }, { "offsetInBeginSection": 1517, "offsetInEndSection": 1679, "text": "The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11600725", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 734, "text": "Following accidental or suicidal exposure, these anticholinesterases lead to three well defined neurological syndromes i.e. initial life threatening acute cholinergic crisis which often requires management in intensive care unit, intermediate syndrome in which cranial nerve palsies, proximal muscle weakness and respiratory muscle weakness are common and patients often require respiratory support and delayed organophosphate induced polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11146591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "[Late onset polyneuropathy due to exposure to organophosphates].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10528323", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 236, "text": " Less often a polyneuropathic syndrome of late onset may occur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10528323", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1051, "text": "On electromyography there was sensomotor peripheral polyneuropathy, which was primarily axonal and predominantly motor and distal. Peripheral nerve biopsy confirmed the presence of 'dying back' type axonopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10528323", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1367, "text": "Agricultural workers chronically exposed to organophosphate insecticides, without adequate protection, have an increased risk of developing late onset neuropathy due to organophosphates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10528323", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 750, "text": "Epidemiologic studies on pesticides have found associations with long-term effects on health mainly in three fields: cancer (especially hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral hazards, Parkinson's disease), and reproductive disorders (infertility, birth defects, adverse pregnancy outcomes, perinatal mortality). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9592856", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 1015, "text": "EMG studies showed evidence of partial denervation of the anterior tibial group of muscles and flexor digiti minimi in 2 of the 30 workers (6.7%) who underwent EMG examination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9311548", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 737, "text": "Neurological symptoms consist in cerebro-organic disfunctions, locomotory disorders reminiscent of multiple sclerosis or M. Parkinson, and sensory, motoric and vegetative polyneuropathy, leading, for instance, to cardiovascular regulatory disorder like sympathicotonia or, orthostatic hypotonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7787373", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 972, "text": "Thirty percent of patients had definite or possible exposure to organophosphate pesticides, and the peak use coincides with the peak incidence of Guillain-Barr\u00e9 syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7998771", "endSection": "abstract" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1289, "text": "These results suggest that previously reported cases of organophosphate-induced delayed polyneuropathy may represent only the worst disease in a spectrum of impairment, a sequela of exposure that may be much more common than previously thought.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8160653", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 367, "text": "It is suggested that the main cause of nervous lesions in these cases was the complex effect of pesticides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1481520", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 415, "text": "Delayed polyneuropathy develops within 1 to 3 weeks and abates after 6 to 12 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1665780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Isolated case reports have circumstantially linked the use of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) to polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2158793", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1117, "text": "Thus, the weight of evidence indicates that 2,4-D is an unlikely cause of polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2158793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "A patient is reported presenting a cerebellar disorder developing about 5 weeks after acute exposure to an organophosphate insecticide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2707289", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 364, "text": "Less well known, but more complex and idiosyncratic, is the potential for some agents to produce a delayed and progressive polyneuropathy--Organophosphorus Induced Delayed Neurotox-icity (OPIDN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2462700", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1570, "text": " It is also quite probable that human neurotoxicity may be a potential hazard from exposure to more than the handful of organophosphorus pesticides that have been described in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2462700", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 601, "text": "In the present study the electroencephalograms of 3 of a group 10 workmen, who had been continually exposed to hexachlorcyclohexane, show pathological findings. The electromyograms of 8 of these 10 workman demonstrate a disturbance of the peripherical motoneuron. All probands, who exhibit o pathological EEG, also show a polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6179111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Many organophosphorus compounds, including the organophosphate insecticides, may cause polyneuropathy of delayed onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7194975", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 333, "text": "Nevertheless, we describe a patient with delayed polyneuropathy after suicidal ingestion of parathion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7194975", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 186, "text": "Following acute organophosphorus (OP) poisoning patients complain of numbness without objective sensory abnormalities or other features of OP induced delayed polyneuropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185328", "endSection": "abstract" } ] }, { "body": "What is the methodological principle of ChIA-PET?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20181287", "http://www.ncbi.nlm.nih.gov/pubmed/25563301", "http://www.ncbi.nlm.nih.gov/pubmed/22564980", "http://www.ncbi.nlm.nih.gov/pubmed/24051548", "http://www.ncbi.nlm.nih.gov/pubmed/22926262", "http://www.ncbi.nlm.nih.gov/pubmed/25114054" ], "ideal_answer": [ "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. To minimize non-specific noise and reduce complexity, as well as to increase the specificity of the chromatin interaction analysis, chromatin immunoprecipitation (ChIP) is used against specific protein factors to enrich chromatin fragments of interest before proximity ligation. Combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors. Here, we propose a statistical model taking into account the genomic distance relationship, as well as the general propensity of anchors to be involved in contacts overall.", "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. It converts functional chromatin structure into millions of short tag sequences. By combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors." ], "type": "summary", "id": "56f3f94109dd18d46b000001", "snippets": [ { "offsetInBeginSection": 574, "offsetInEndSection": 750, "text": "Overall we show that ChIA-PET is the cornerstone to explore the three-dimensional (3D) chromatin structure, and certainly will lead the forthcoming wave of 3D genomics studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25563301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20181287", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 688, "text": "Chromatin Interaction Analysis using Paired-End Tag sequencing (ChIA-PET) is a method which converts functional chromatin structure into millions of short tag sequences. Combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22926262", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 539, "text": "Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) was developed to identify these higher-order chromatin structures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22564980", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 392, "text": " ChIA-PET is a novel method to identify such interactions, where physical contacts between regions bound by a specific protein are quantified using next-generation sequencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25114054", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1062, "text": "Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24051548", "endSection": "abstract" } ] }, { "body": "Is there an association between borna virus and brain tumor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10483922", "http://www.ncbi.nlm.nih.gov/pubmed/10227422", "http://www.ncbi.nlm.nih.gov/pubmed/1731117", "http://www.ncbi.nlm.nih.gov/pubmed/17020949", "http://www.ncbi.nlm.nih.gov/pubmed/17306587", "http://www.ncbi.nlm.nih.gov/pubmed/11507219", "http://www.ncbi.nlm.nih.gov/pubmed/11070091", "http://www.ncbi.nlm.nih.gov/pubmed/21937656", "http://www.ncbi.nlm.nih.gov/pubmed/8917593", "http://www.ncbi.nlm.nih.gov/pubmed/15596826", "http://www.ncbi.nlm.nih.gov/pubmed/8184547", "http://www.ncbi.nlm.nih.gov/pubmed/10518583", "http://www.ncbi.nlm.nih.gov/pubmed/11907227", "http://www.ncbi.nlm.nih.gov/pubmed/22848506" ], "ideal_answer": [ "There is no data to suggest an association between borna virus and brain tumor. Borna disease virus establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures causing cellular damage. Infected neural cells, include astrocytes, neurons, oligodendroglioma cell line. Borna disease virus replicates and can cause damage of brain cells." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001890", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001891", "http://www.disease-ontology.org/api/metadata/DOID:1319", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932", "http://www.disease-ontology.org/api/metadata/DOID:5154" ], "type": "yesno", "id": "530f685c329f5fcf1e000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Borna disease virus (BDV), a nonsegmented, negative-strand RNA virus, infects a wide variety of mammalian species and readily establishes a long-lasting, persistent infection in brain cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21937656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "To investigate the biological characteristics of field isolates of Borna disease virus (BDV), as well as to understand BDV infections outside endemic countries, we isolated the virus from brain samples of a heifer with Borna disease in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17306587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to the certain neuronal populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17020949", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1677, "text": "In addition, compared to uninfected mixed cultures, activation of microglia in BDV-infected mixed cultures was associated with a significantly greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1beta, and interleukin 10. Taken together, the present data are the first in vitro evidence that persistent BDV infection of neurons and astrocytes rather than direct exposure to the virus or dying neurons is critical for activating microglia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17020949", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 708, "text": "Usually, Borna disease virus is not cleared from the brain but rather persists in neural cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15596826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Varied persistent life cycles of Borna disease virus in a human oligodendroglioma cell line.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11907227", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Borna disease virus (BDV) establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11907227", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1719, "text": "Thus, our findings show that BDV may have established a persistent infection at low levels of viral expression in OL cells with the possibility of a latent infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11907227", "endSection": "abstract" }, { "offsetInBeginSection": 1726, "offsetInEndSection": 1899, "text": "These results suggested that BDV infection may cause direct damage in the developing brain by inhibiting the function of amphoterin due to binding by the p24 phosphoprotein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11507219", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 462, "text": "We describe a model for investigating disorders of central nervous system development based on neonatal rat infection with Borna disease virus, a neurotropic noncytolytic RNA virus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10518583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10483922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Borna disease virus (BDV) causes central nervous system (CNS) disease in several vertebrate species, which is frequently accompanied by behavioral abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10227422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Intrinsic responses to Borna disease virus infection of the central nervous system.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8917593", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Immune cells invading the central nervous system (CNS) in response to Borna disease virus (BDV) antigens are central to the pathogenesis of Borna disease (BD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8917593", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 439, "text": "We report here the partial purification and characterization of cell-free BDV from the tissue culture supernatant of infected human neuroblastoma SKNSH cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8184547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "We have used the reverse transcriptase-polymerase chain reaction technique to gain insight into the pathogenesis of encephalitis caused by Borna disease virus (BDV). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1731117", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1064, "text": "In contrast, in the BDV-infected primary mixed cultures, we observed proliferation of microglia cells that acquired the round morphology and expressed major histocompatibility complex molecules of classes I and II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17020949", "endSection": "abstract" } ] }, { "body": "List medication interfering with purine metabolism that are used for treatment of T-cell prolymphocytic leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18039954", "http://www.ncbi.nlm.nih.gov/pubmed/22538464", "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "http://www.ncbi.nlm.nih.gov/pubmed/19915381", "http://www.ncbi.nlm.nih.gov/pubmed/18309944", "http://www.ncbi.nlm.nih.gov/pubmed/19778847", "http://www.ncbi.nlm.nih.gov/pubmed/19275513", "http://www.ncbi.nlm.nih.gov/pubmed/12447847", "http://www.ncbi.nlm.nih.gov/pubmed/8468724", "http://www.ncbi.nlm.nih.gov/pubmed/15869731", "http://www.ncbi.nlm.nih.gov/pubmed/22483155", "http://www.ncbi.nlm.nih.gov/pubmed/9215839", "http://www.ncbi.nlm.nih.gov/pubmed/15039804" ], "ideal_answer": [ "Deoxycoformycin and pentostatin are purine analogs that interfere with purine metabolism and are used for treatment of T-cell prolymphocytic leukemia patients." ], "exact_answer": [ [ "deoxycoformycin" ], [ "pentostatin" ], [ "nelarabine" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008660", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006144", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042278", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006163", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011684", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011687" ], "type": "list", "id": "530cefaaad0bf1360c00000c", "snippets": [ { "offsetInBeginSection": 259, "offsetInEndSection": 382, "text": "Treatment with purine analogues and alemtuzumab has resulted in significantly higher response rates and improved survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19778847", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 438, "text": " Treatment with purine analogs and the monoclonal antibody alemtuzumab has resulted in significantly higher response rates and increased survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19275513", "endSection": "abstract" }, { "offsetInBeginSection": 1671, "offsetInEndSection": 1888, "text": "Nelarabine is an effective regimen against indolent leukemias, and combining it with fludarabine was most promising. Determination of tumor cell ara-GTP levels may provide a predictive test for response to nelarabine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18309944", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 483, "text": "T-cell prolymphocytic leukemia has an aggressive course with short median survival and poor response to chemotherapy. With the use of the purine analogue pentostatin more than half of patients will have a major response and a minority will have a complete remission, usually lasting months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15869731", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 339, "text": " T-cell prolymphocytic leukaemia (T-PLL) is a rare post-thymic T-cell malignancy with an aggressive clinical course. It has generally been resistant to alkylating chemotherapy, but some effect has been observed with the purine analog 2-deoxycoformicin with documented partial or complete response rates in up to 45% of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15039804", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 418, "text": "Fifteen patients with T-PLL, most of whom had received the purine analog deoxycoformycin (DCF), were treated with CAMPATH-1H.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9215839", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 849, "text": "Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8468724", "endSection": "abstract" }, { "offsetInBeginSection": 2693, "offsetInEndSection": 2911, "text": "Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8468724", "endSection": "abstract" } ] }, { "body": "Does PU.1 (SPI1) affect NF-kB binding?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19966852", "http://www.ncbi.nlm.nih.gov/pubmed/12020825", "http://www.ncbi.nlm.nih.gov/pubmed/7678251", "http://www.ncbi.nlm.nih.gov/pubmed/21245163", "http://www.ncbi.nlm.nih.gov/pubmed/8647196", "http://www.ncbi.nlm.nih.gov/pubmed/10023076" ], "ideal_answer": [ "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs). Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified.", "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs)." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016328" ], "type": "yesno", "id": "56e05a7b51531f7e3300000d", "snippets": [ { "offsetInBeginSection": 260, "offsetInEndSection": 528, "text": "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21245163", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 532, "text": "Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12020825", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1171, "text": "As little as 82 bp of upstream sequence gave relatively strong luciferase activity, a region containing both a PU.1 and NF-kB site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12020825", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1236, "text": "Potential transcription regulatory elements, AP1, AP2, AP3, NF-kB and GATA recognition sequences, are located within 523 bp upstream of the p35 gene; however, no TATA box was identified. The p40 subunit gene consists of eight exons. A TATA box is located 30 bp upstream from the transcription start site, and AP1, AP3, GATA, and Pu.1 recognition sequences are located within 690 bp upstream of the p40 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8647196", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1177, "text": "Several putative binding sequences for ubiquitous (Sp1, AP-1, AP-2, and NF-kB) and leukocyte-specific (PU.1) transcription factors have been identified in the proximal region of the CD11c promoter which may participate in the regulation of the expression of p150,95.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7678251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "PU.1 is regulated by NF-kappaB through a novel binding site in a 17 kb upstream enhancer element.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19966852", "endSection": "title" } ] }, { "body": "Does the majority of the mitochondrial genomes abide to the second parity rule (PR2)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "http://www.ncbi.nlm.nih.gov/pubmed/17562011", "http://www.ncbi.nlm.nih.gov/pubmed/11675596" ], "ideal_answer": [ "A large number of mitochondrial genomes significantly deviate from the 2nd parity rule, in contrast to the eubacterial ones. This behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054629", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000262" ], "type": "yesno", "id": "55423fc0ed966d112c000001", "snippets": [ { "offsetInBeginSection": 465, "offsetInEndSection": 587, "text": "a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 803, "text": "mitochondria may be divided into three distinct sub-groups according to their overall deviation from the aforementioned parity rule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1284, "text": "The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 659, "text": "We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1283, "text": "The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 660, "text": "We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1283, "text": "The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 659, "text": "We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" } ] }, { "body": "What is the association between h-index and academic rank in academic neurosurgery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23820322", "http://www.ncbi.nlm.nih.gov/pubmed/23079075", "http://www.ncbi.nlm.nih.gov/pubmed/22381859", "http://www.ncbi.nlm.nih.gov/pubmed/20469986", "http://www.ncbi.nlm.nih.gov/pubmed/19392590", "http://www.ncbi.nlm.nih.gov/pubmed/24055571", "http://www.ncbi.nlm.nih.gov/pubmed/23886815", "http://www.ncbi.nlm.nih.gov/pubmed/22544537", "http://www.ncbi.nlm.nih.gov/pubmed/23870040", "http://www.ncbi.nlm.nih.gov/pubmed/24239737", "http://www.ncbi.nlm.nih.gov/pubmed/20380531", "http://www.ncbi.nlm.nih.gov/pubmed/23872122", "http://www.ncbi.nlm.nih.gov/pubmed/21495810" ], "ideal_answer": [ "Greater h-index is associated with greater academic rank in academic neurosurgery. The h indices increased significantly with increasing academic rank, with the median for instructors, assistant professors, associate professors, and professors was shown to be 2, 5, 10, and 19, respectively. In addition, h-index was shown to be predictive of NIH funding, fellowship training, academic productivity and salary." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009493", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000043" ], "type": "summary", "id": "530cefaaad0bf1360c00000b", "snippets": [ { "offsetInBeginSection": 944, "offsetInEndSection": 1037, "text": " The contemporary h-index was found to be significantly predictive of NIH funding (p<0.001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24239737", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1493, "text": "Bibliometric indices are higher for those with NIH funding compared to those without, but only the contemporary h-index was shown to be predictive of NIH funding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24239737", "endSection": "abstract" }, { "offsetInBeginSection": 1513, "offsetInEndSection": 1650, "text": "However, when stratified by academic rank, a trend was observed showing greater mean h-index scores for those who completed fellowships. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055571", "endSection": "abstract" }, { "offsetInBeginSection": 1704, "offsetInEndSection": 1834, "text": "Overall, being a senior faculty member corresponds with a greater h-index score, regardless of whether a fellowship was completed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055571", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 958, "text": "There was a positive association between the h-index, academic rank, and years posttraining.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23872122", "endSection": "abstract" }, { "offsetInBeginSection": 1467, "offsetInEndSection": 1651, "text": "Application of the h-index as a bibliometric in neurosurgery can distinguish academic productivity on the basis of academic rank, years posttraining, and neurosurgical subspecialties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23872122", "endSection": "abstract" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1217, "text": "Overall, the authors conclude that the h index metric is a reasonable measure of academic productivity in the pediatric neurosurgery arena that provides a robust measure of an individual's contribution to the pediatric neurosurgery literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23870040", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1490, "text": "The h index calculation also reveals the productivity of the pediatric neurosurgeons to be on par with the productivity of neurosurgeons in general.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23870040", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 803, "text": "The h-index frequency distribution conformed to both the log-linear variation of a power law (r (2)\u2009=\u2009.99) and the beta distribution with the same fitting exponents as previously described in a power law analysis of the productivity of neurosurgeons. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544537", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 1275, "text": "The h indices increased significantly with increasing academic rank, with the median for instructors, assistant professors, associate professors, and professors being 2, 5, 10, and 19, respectively (p < 0.0001, Kruskal-Wallis; all groups significantly different from each other except the difference between instructor and assistant professor [Conover]). Departmental chairs had a median h index of 22 (range 3-55) and program directors a median of 17 (range 0-62). Plot of the log of the rank versus h index demonstrated a remarkable linear pattern (R(2) = 0.995, p < 0.0001), suggesting that this is a power-law relationship.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20469986", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1559, "text": "The distribution of the h index within an academic population is described for the first time and appears related to the ubiquitous power-law distribution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20469986", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1301, "text": "As expected, the h index increased with academic rank and there was a statistically significant difference between each rank. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19392590", "endSection": "abstract" }, { "offsetInBeginSection": 1795, "offsetInEndSection": 2034, "text": "Within the field of academic neurosurgery, clear differences of h indices between academic ranks exist. On average, an increase of the h index by 5 appears to correspond to the next highest academic rank, with the exception of chairperson.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19392590", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1536, "text": "Scopus h-index was of borderline significance in predicting physician salary (P = 0.12). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23820322", "endSection": "abstract" } ] }, { "body": "Is there an association between bruxism and reflux?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22926484", "http://www.ncbi.nlm.nih.gov/pubmed/15520695", "http://www.ncbi.nlm.nih.gov/pubmed/19089153", "http://www.ncbi.nlm.nih.gov/pubmed/23738993", "http://www.ncbi.nlm.nih.gov/pubmed/22156738", "http://www.ncbi.nlm.nih.gov/pubmed/24011800", "http://www.ncbi.nlm.nih.gov/pubmed/14655925", "http://www.ncbi.nlm.nih.gov/pubmed/21248360", "http://www.ncbi.nlm.nih.gov/pubmed/19830044", "http://www.ncbi.nlm.nih.gov/pubmed/841409" ], "ideal_answer": [ "Yes, bruxism is associated with reflux. Sleep bruxism is prevalent in GERD patients." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020186", "http://www.disease-ontology.org/api/metadata/DOID:2846", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002012", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005764", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001244", "http://www.disease-ontology.org/api/metadata/DOID:8534" ], "type": "yesno", "id": "530cefaaad0bf1360c00000f", "snippets": [ { "offsetInBeginSection": 1564, "offsetInEndSection": 1647, "text": "Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24011800", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1219, "text": "There was a statistical trend towards tooth wear progression being associated with gastric risk factors (p < 0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22156738", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 482, "text": "This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21248360", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 741, "text": "RMMA episodes including SB were induced by esophageal acidification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21248360", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 224, "text": "Chronic regurgitation of gastric acids in patients with gastroesophageal reflux disease may cause dental erosion, which can lead in combination with attrition or bruxism to extensive loss of coronal tooth tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830044", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 489, "text": "This clinical report describes treatment of severe tooth wear of a gastroesophageal reflux disease patient who is 54-year-old Turkish male patient. After his medical treatment, severe tooth wear, bruxism and decreased vertical dimensions were determined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830044", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1084, "text": "Gastroesophageal reflux disease by itself or in combination with attrition, abrasion or bruxism may be responsible for the loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830044", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 910, "text": "The association between bruxism, feeding and smoking habits and digestive disorders may lead to serious consequences to dental and related structures, involving dental alterations (wear, fractures and cracks), periodontal signs (gingival recession and tooth mobility) and muscle-joint sensitivity, demanding a multidisciplinary treatment plan. This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19089153", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 683, "text": "The frequencies of RMMA, single short-burst, and clenching episodes were significantly higher during decreased esophageal pH episodes than those during other times. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520695", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 988, "text": "These results suggest that most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520695", "endSection": "abstract" }, { "offsetInBeginSection": 2192, "offsetInEndSection": 2328, "text": "Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14655925", "endSection": "abstract" } ] }, { "body": "What is known about the value of mindfulness interventions in prostate cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16685074", "http://www.ncbi.nlm.nih.gov/pubmed/14749092", "http://www.ncbi.nlm.nih.gov/pubmed/22442202", "http://www.ncbi.nlm.nih.gov/pubmed/22853988", "http://www.ncbi.nlm.nih.gov/pubmed/7776900", "http://www.ncbi.nlm.nih.gov/pubmed/18400281", "http://www.ncbi.nlm.nih.gov/pubmed/23442556", "http://www.ncbi.nlm.nih.gov/pubmed/21625914", "http://www.ncbi.nlm.nih.gov/pubmed/12883107", "http://www.ncbi.nlm.nih.gov/pubmed/11696736", "http://www.ncbi.nlm.nih.gov/pubmed/17521871" ], "ideal_answer": [ "In prostate cancer patients, mindfulness interventions were well accepted and were effective in reducing stress, anxiety, avoidance, fear of cancer recurrence, cortisol levels and blood pressure, and improving quality of life, sleep quality and immune system functioning. In addition, mindfulness interventions promoted initiation of healthy dietary changes and decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064866" ], "type": "summary", "id": "54f09a5894afd6150400001c", "snippets": [ { "offsetInBeginSection": 1136, "offsetInEndSection": 1718, "text": "Participants reported regular mindfulness training practice, and there was a significant correlation between mindfulness training practice and changes in both initiation and maintenance of the change in A:V. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes mindfulness training in supporting dietary change for men with recurrent prostate cancer and invite further study to explore the possible role of mindfulness training as a means of supporting both initiation of dietary changes and maintenance of those changes over time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22853988", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 1428, "text": "FINDINGS: Following the 6-week MBSR program, patients showed improvements in stress and anxiety (p < .05); caregivers' psychological and QOL also improved but were not statistically significant. Both patients and caregivers had decreases in cortisol at Weeks 1 and 3 (p < .05) but not at Week 6. Similar to cortisol levels at Week 6, salivary interleukin-6 levels were lower overall (before/after an MBSR-C session), compared with Week 1 for patients and caregivers. CONCLUSIONS: MBSR-C may be a beneficial intervention for reducing stress, anxiety, cortisol levels, and symptoms in advanced-stage cancer patients and may also benefit caregivers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22442202", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 931, "text": "ESULTS: Significant improvements were observed for anxiety (p = 0.027), avoidance (p = 0.032), and mindfulness skills (p = 0.019), with a trend for a reduction in fear of cancer recurrence (p = 0.062).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21625914", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1317, "text": "CONCLUSIONS: Mindfulness-based group interventions appear to have utility in this patient group and show promise for reducing anxiety, avoidance, and fear of cancer recurrence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21625914", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1625, "text": " Linear mixed modeling showed significant improvements in overall symptoms of stress which were maintained over the follow-up period. Cortisol levels decreased systematically over the course of the follow-up. Immune patterns over the year supported a continued reduction in Th1 (pro-inflammatory) cytokines. Systolic blood pressure (SBP) decreased from pre- to post-intervention and HR was positively associated with self-reported symptoms of stress. CONCLUSIONS: MBSR program participation was associated with enhanced quality of life and decreased stress symptoms, altered cortisol and immune patterns consistent with less stress and mood disturbance, and decreased blood pressure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17521871", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1077, "text": "Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality, but these improvements were not significantly correlated with the degree of program attendance or minutes of home practice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14749092", "endSection": "abstract" }, { "offsetInBeginSection": 1747, "offsetInEndSection": 2001, "text": "CONCLUSIONS: MBSR program enrollment was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients, and resulted in possibly beneficial changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14749092", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 1142, "text": "Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality. Although there were no significant changes in the overall number of lymphocytes or cell subsets, T cell production of IL-4 increased and IFN-gamma decreased, whereas NK cell production of IL-10 decreased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12883107", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1542, "text": "CONCLUSIONS: MBSR participation was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients. This study is also the first to show changes in cancer-related cytokine production associated with program participation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12883107", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1638, "text": "CONCLUSIONS: Our small study provides evidence that a plant-based diet delivered in the context of MBSR decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11696736", "endSection": "abstract" } ] }, { "body": "What is known about prostate cancer screening in the UK ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20507844", "http://www.ncbi.nlm.nih.gov/pubmed/11002455", "http://www.ncbi.nlm.nih.gov/pubmed/12614245", "http://www.ncbi.nlm.nih.gov/pubmed/10185137", "http://www.ncbi.nlm.nih.gov/pubmed/21047592", "http://www.ncbi.nlm.nih.gov/pubmed/12587941", "http://www.ncbi.nlm.nih.gov/pubmed/10682690", "http://www.ncbi.nlm.nih.gov/pubmed/15049981", "http://www.ncbi.nlm.nih.gov/pubmed/15946386", "http://www.ncbi.nlm.nih.gov/pubmed/17309171", "http://www.ncbi.nlm.nih.gov/pubmed/19138385", "http://www.ncbi.nlm.nih.gov/pubmed/22952783", "http://www.ncbi.nlm.nih.gov/pubmed/16978272", "http://www.ncbi.nlm.nih.gov/pubmed/19021912", "http://www.ncbi.nlm.nih.gov/pubmed/16720000", "http://www.ncbi.nlm.nih.gov/pubmed/23728749" ], "ideal_answer": [ "There is still no national screening programme established in the UK. Prostate cancer screening of asymptomatic men is not recommended by the National Screening Council at present and is not encouraged in the NHS. However, PSA tests are being performed for prostate cancer screening. The CAP and ProtecT trials are aimed to evaluate prostate cancer screening in the UK." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011471", "http://www.disease-ontology.org/api/metadata/DOID:10286", "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055088", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008403" ], "type": "summary", "id": "530cefaaad0bf1360c00000e", "snippets": [ { "offsetInBeginSection": 95, "offsetInEndSection": 243, "text": "Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Latest results from the UK trials evaluating prostate cancer screening and treatment: the CAP and ProtecT studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047592", "endSection": "title" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1738, "text": "The CAP and ProtecT trials (ISRCTN92187251 and ISRCTN20141217) will help resolve the prostate cancer screening debate, define the optimum treatment for localised disease and generate evidence to improve men's health.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047592", "endSection": "abstract" }, { "offsetInBeginSection": 1686, "offsetInEndSection": 1818, "text": "Increased usage of Prosdex leads to more informed decision making, the key aim of the UK Prostate Cancer Risk Management Programme. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507844", "endSection": "abstract" }, { "offsetInBeginSection": 1343, "offsetInEndSection": 1663, "text": "To date, the AIDIT team has established a website to facilitate communication between project collaborators (www.impact-study.co.uk), has been represented at several international meetings and has facilitated a conference for the IMPACT study to bring together international research teams, clinicians and policy makers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17309171", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 474, "text": " This prospective questionnaire study was nested within the case-finding component of the ProtecT (prostate testing for cancer and treatment) feasibility study (ISRCTN20141297). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16978272", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 247, "text": "The UK NHS Executive has issued extensive guidance stressing the importance of adequate counselling prior to performing this test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16720000", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 187, "text": "To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15049981", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 1322, "text": "In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15049981", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1545, "text": "These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15049981", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 249, "text": "There is no current prostate cancer screening programme in the UK. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12614245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Prostate cancer screening of asymptomatic men is not recommended by the National Screening Council at present and is not encouraged in the NHS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12587941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10682690", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1063, "text": "Some respondents were reluctant to give the leaflet to people enquiring about screening for prostate cancer, for example, because they thought that the leaflet would cause anxiety, or because prostate cancer screening was not freely available locally. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10185137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "National guidance (executive letter) EL(97)12 stated that population screening should not be provided by the NHS, or be offered to the public until there is effective screening technology for prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11002455", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 653, "text": "This postal questionnaire survey reveals that 81% (95% CI 75% to 87%) of responding general practitioners in North Staffordshire agreed with EL(97)12 and one in ten said that the executive letter changed their views, suggesting that such national guidance has an effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11002455", "endSection": "abstract" } ] }, { "body": "Which hormone abnormalities are common in Williams syndrome ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21209713", "http://www.ncbi.nlm.nih.gov/pubmed/23734615", "http://www.ncbi.nlm.nih.gov/pubmed/18204753", "http://www.ncbi.nlm.nih.gov/pubmed/22719898", "http://www.ncbi.nlm.nih.gov/pubmed/7789182", "http://www.ncbi.nlm.nih.gov/pubmed/10378390", "http://www.ncbi.nlm.nih.gov/pubmed/15751610", "http://www.ncbi.nlm.nih.gov/pubmed/16181239", "http://www.ncbi.nlm.nih.gov/pubmed/20301427", "http://www.ncbi.nlm.nih.gov/pubmed/20425788", "http://www.ncbi.nlm.nih.gov/pubmed/16473313", "http://www.ncbi.nlm.nih.gov/pubmed/16596673", "http://www.ncbi.nlm.nih.gov/pubmed/15108207", "http://www.ncbi.nlm.nih.gov/pubmed/3164411", "http://www.ncbi.nlm.nih.gov/pubmed/17188616", "http://www.ncbi.nlm.nih.gov/pubmed/1867260", "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "http://www.ncbi.nlm.nih.gov/pubmed/3405972", "http://www.ncbi.nlm.nih.gov/pubmed/8835601" ], "ideal_answer": [ "Thyroid hormone abnormalities are common in Williams syndrome. Oxytocin and vasopressin, cortisol, growth hormone and calcitonin were also implicated in the Williams syndrome." ], "exact_answer": [ "thyroid" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018980", "http://www.disease-ontology.org/api/metadata/DOID:1928", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006728" ], "type": "factoid", "id": "530cefaaad0bf1360c00000d", "snippets": [ { "offsetInBeginSection": 302, "offsetInEndSection": 768, "text": "WS and TD participants had similar profiles in a familiar setting, while participants with WS had elevated cortisol late in the day in the novel setting when social demands were higher. The cortisol awakening response in WS was associated with parent-reported levels of somatic complaints and social difficulties. Results suggest that adults with WS have a typical diurnal cortisol profile that may be sensitive to social and activity transitions throughout the day.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23734615", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1636, "text": "Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22719898", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 487, "text": "Three quarters of the WS subjects showed abnormal glucose curves, meeting diagnostic criteria for either diabetes or the pre-diabetic state of impaired glucose tolerance. Fasting mean glucose and median insulin levels did not differ significantly in the total WS cohort versus age-gender-BMI matched controls, though the glucose area under the curve was greater in the WS subjects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20425788", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 467, "text": "Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvular aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 913, "text": "In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a low FT(4) concentration (10.21 pmol/l; normal range: 10.29-24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas (99m)Tc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1427, "text": "Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 418, "text": "As growth hormone (GH) deficiency was diagnosed by an additional GH-stimulation test, we commenced with a GH-treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18204753", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 626, "text": "None of our patients had overt hypothyroidism; 29 patients (31.5%) had subclinical hypothyroidism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17188616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Thyroid involvement in Williams syndrome (WS) was recently reported in two small groups of patients, both showing an increased prevalence of elevation of TSH serum concentration; in one of the two reports, 70% of the patients demonstrated a hypoplasia of thyroid gland as well. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596673", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 829, "text": "Our study confirms the increased incidence of both elevated TSH serum values (37.9% in our sample) and thyroid gland hypoplasia (74.7%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596673", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 439, "text": "A WS patient with CPP is presented, whose pubertal development and bone age progression were arrested by administration of GnRH analogues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16473313", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1354, "text": " This study confirms the presence of alterations of thyroid function in WS and also suggests the frequent occurrence of abnormalities of thyroid morphology in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16181239", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 513, "text": "We report a female infant with confirmed WBS who, through provocative testing, was found to have GHD and who responded satisfactorily to hGH therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15751610", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1040, "text": "In conclusion, GH deficiency might contribute to the growth failure in a number of patients with WBS and in such cases hGH therapy will most likely improve final height.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15751610", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 697, "text": "Thyrotropin level was very high (>50 microU/ml; normal value 0.2-4 microU/ml), while serum free T(3) (FT3) and free T(4) (FT4) levels were normal (FT3 3.6 pg/ml, normal value 2.8-5.6 pg/ml; FT4 11.6 pg/ml, normal value 6.6-14 pg/ml); antithyroid autoantibodies were absent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108207", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1330, "text": "Recently a case of thyroid hemiagenesis in a child with WS has been reported; our patient underscores the association of hypothyroidism and WS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 microU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 707, "text": "TSH response to thyrotropin-releasing hormone (TRH) injection (200 microg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6-2.2]. These abnormalities are similar to those seen in patients with hypothalamic hypothyroidism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 930, "text": "However, abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis and thyroid dysgenesis have been found in other WS cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 412, "text": "We report a boy with confirmed Williams-Beuren syndrome, who was found to have classical growth hormone deficiency and responded well to growth hormone therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10378390", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 647, "text": "Although growth hormone deficiency is not likely to be a common cause of short stature in Williams-Beuren syndrome, we nevertheless recommend evaluation of the growth hormone-insulin-like growth factor I axis in all cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10378390", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 488, "text": "Endocrinological examinations revealed hypergonadotropic hypogonadism. Prolonged and exaggerated responses of adrenocorticotropin (ACTH) to insulin-induced hypoglycemia and corticotropin releasing hormone (CRH) were also noted. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8835601", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 387, "text": "Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1867260", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1202, "text": "These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1867260", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 222, "text": "It has been suggested that a defect in calcitonin function may play a role in Williams syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3164411", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 559, "text": " These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion, compared with a group of seven normal children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 988, "text": "Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "endSection": "abstract" }, { "offsetInBeginSection": 2146, "offsetInEndSection": 2494, "text": "Additional periodic evaluations during childhood: serum concentration of calcium, thyroid function, hearing, and renal and bladder ultrasound examination. Periodic evaluations during adulthood: glucose tolerance; cardiac evaluation for mitral valve prolapse, aortic insufficiency, and arterial stenosis; and ophthalmologic evaluation for cataracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301427", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1188, "text": "Subclinical hypothyroidism is a frequent but stable finding in young children with WS. The great majority of patients with WS >10 years, either with normal or hypoplastic thyroid, have normal thyroid function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17188616", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 521, "text": " Three cases (15%) of subclinical hypothyroidism were identified. Overt hypothyroidism was diagnosed in two cases (10%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16181239", "endSection": "abstract" } ] }, { "body": "The secreted frizzled-related protein 3 (sFPR3) is altered in human cancers.\nAre its level found to increase or to decrease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23408665", "http://www.ncbi.nlm.nih.gov/pubmed/20160027", "http://www.ncbi.nlm.nih.gov/pubmed/21494614", "http://www.ncbi.nlm.nih.gov/pubmed/17420170", "http://www.ncbi.nlm.nih.gov/pubmed/17702698", "http://www.ncbi.nlm.nih.gov/pubmed/11798016", "http://www.ncbi.nlm.nih.gov/pubmed/17079093", "http://www.ncbi.nlm.nih.gov/pubmed/16266997" ], "ideal_answer": [ "SFRPs are down-regulated in several cancers and this is often correlated with poor prognosis, as has been shown for breast, colorectal, and a number of other cancers. (PMID: 21494614) We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. (PMID: 20160027)", "Secreted frizzled-related protein 3 is potentially acting as a tumor suppressor gene, thus it is down-regulated (decreased) in some cancers." ], "type": "summary", "id": "5159502dd24251bc0500009b", "snippets": [ { "offsetInBeginSection": 238, "offsetInEndSection": 419, "text": "We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20160027", "endSection": "sections.0" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1484, "text": "In conclusion, this is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20160027", "endSection": "sections.0" }, { "offsetInBeginSection": 486, "offsetInEndSection": 562, "text": "secreted frizzled-related protein-3 were produced by multiple myeloma cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702698", "endSection": "sections.0" }, { "offsetInBeginSection": 1837, "offsetInEndSection": 1908, "text": "these data suggest a tumor-suppressive potential for FRZB/sFRP3 in OGS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17079093", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "The ability of Frzb/secreted Frizzled-related protein 3 (sFRP3) to inhibit Wnt signaling and the localization of Frzb/sFRP3 on chromosome 2q to a region frequently deleted in cancers have led some investigators to hypothesize that Frzb/sFRP3 is a tumor suppressor gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16266997", "endSection": "sections.0" }, { "offsetInBeginSection": 1575, "offsetInEndSection": 1784, "text": "Together, these data suggest that Frzb/sFRP3 and DN-LRP5 exhibit antitumor activity through the reversal of epithelial-to-mesenchymal transition and inhibition of MMP activities in a subset of prostate cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16266997", "endSection": "sections.0" }, { "offsetInBeginSection": 443, "offsetInEndSection": 531, "text": "secreted frizzled related protein (hsFRP) was found to be down-regulated in some cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11798016", "endSection": "sections.0" }, { "offsetInBeginSection": 597, "offsetInEndSection": 640, "text": "hsFRP is a potential tumor suppressor gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11798016", "endSection": "sections.0" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1274, "text": "All these cases were associated with either up-regulation of FzE3 or down-regulation of hsFRP", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11798016", "endSection": "sections.0" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1406, "text": "Since modified Wnt signaling and down-regulation of frizzled-related proteins have been observed in many human cancers, this variant may also affect the susceptibility to other cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17420170", "endSection": "sections.0" } ] }, { "body": "Albumin depletion is a common first step for proteomic analysis of CSF fluid. What is the advantage and disadvantage of this procedure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18288611", "http://www.ncbi.nlm.nih.gov/pubmed/16335978", "http://www.ncbi.nlm.nih.gov/pubmed/15952730", "http://www.ncbi.nlm.nih.gov/pubmed/18412540", "http://www.ncbi.nlm.nih.gov/pubmed/19327347", "http://www.ncbi.nlm.nih.gov/pubmed/15822917", "http://www.ncbi.nlm.nih.gov/pubmed/21906361", "http://www.ncbi.nlm.nih.gov/pubmed/23300121" ], "ideal_answer": [ "Depletion of the high abundant protein Albumin from CSF samples is improving the detection of lower abundant proteins but may also lead to the potential loss of non-target proteins." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005441", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000418", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0033326" ], "type": "summary", "id": "515a9d86d24251bc050000a7", "snippets": [ { "offsetInBeginSection": 206, "offsetInEndSection": 436, "text": "However, albumin binds peptides and proteins, which raises concerns as to how the removal of albumin could impact the outcome of the biomarker study while ignoring the possibility that this could be a biomarker subproteome itself.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300121", "endSection": "sections.0" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1274, "text": "This study demonstrates that reduction of sample complexity by albumin depletion of CSF can be performed without CV impairment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19327347", "endSection": "sections.0" }, { "offsetInBeginSection": 125, "offsetInEndSection": 350, "text": "We have utilized albumin depletion prior to 2D gel electrophoresis to enhance glycoprotein concentration for image analysis as well as structural glycoprotein determination without glycan release using mass spectrometry (MS).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18288611", "endSection": "sections.0" }, { "offsetInBeginSection": 355, "offsetInEndSection": 543, "text": "The albumin depletion method is the most suitable as prefractionation method of CSF prior to 2-DE for structural determination of glycoproteins in the study of neurodegenerative disorders.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16335978", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 479, "text": "A proper sample preparation, in particular, abundant protein removal is crucial in the characterization of low-abundance proteins including those harboring post-translational modifications. In human cerebrospinal fluid (CSF), approximately 80% of proteins originate from serum, and removal of major proteins is necessary to study brain-derived proteins that are present at low concentrations for successful biomarker and therapeutic target discoveries for neurological disorders.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15952730", "endSection": "sections.0" }, { "offsetInBeginSection": 221, "offsetInEndSection": 590, "text": "The most abundant component in human body fluids, human serum albumin (HSA), is present at concentrations corresponding to approximately 50% of the total protein content in, e.g., plasma and cerebrospinal fluid (CSF). If this component could be selectively removed, then the chances of observing lower-abundance component of clinical interest would be greatly improved.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15822917", "endSection": "sections.0" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1337, "text": ", and the identification of lower abundant components was clearly facilitated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15822917", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 363, "text": "Two different depletion strategies for removing albumin from human cerebrospinal fluid (CSF), Microcon Centrifugal Filter vs. Montage Albumin Deplete kit, were evaluated for improving protein profiling pattern and reproducibility in SELDI analysis. METHODS: Pooled CSF was divided into 20 aliquots and these aliquots were subjected to SELDI analysis ei", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19327347", "endSection": "sections.0" }, { "offsetInBeginSection": 1740, "offsetInEndSection": 1880, "text": "Enhanced identification of lower-abundance components was observed in the depleted fraction, in terms of more detected peptides per protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18412540", "endSection": "sections.0" } ] }, { "body": "How are lincRNA affecting the regulation of gene expression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22403033", "http://www.ncbi.nlm.nih.gov/pubmed/22841487", "http://www.ncbi.nlm.nih.gov/pubmed/23541921", "http://www.ncbi.nlm.nih.gov/pubmed/24268656", "http://www.ncbi.nlm.nih.gov/pubmed/23965803", "http://www.ncbi.nlm.nih.gov/pubmed/23597480", "http://www.ncbi.nlm.nih.gov/pubmed/24080187", "http://www.ncbi.nlm.nih.gov/pubmed/24316222", "http://www.ncbi.nlm.nih.gov/pubmed/24022994" ], "ideal_answer": [ "lincRNA may function either as modulators of epigenetic mark deposition or as endogenous antagonists for microRNA binding. A lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog. Mdig is involved in the regulation of H3K9me3 to influence the heterochromatin structure of the genome and the expression of genes important for cell growth or transformation. Observed biases in lincRNA genomic locations and expression profiles are consistent with some of these lincRNAs being involved in the regulation of neighboring protein-coding genes with developmental functions." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085" ], "type": "summary", "id": "533c3571c45e133714000005", "snippets": [ { "offsetInBeginSection": 259, "offsetInEndSection": 483, "text": "We detected a considerable number of cis expression quantitative trait loci (cis-eQTLs) and demonstrated that the genetic regulation of lincRNA expression is independent of the regulation of neighboring protein-coding genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268656", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 930, "text": "We observe biases in lincRNA genomic locations and expression profiles that are consistent with some of these lincRNAs being involved in the regulation of neighboring protein-coding genes with developmental functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403033", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 337, "text": "In\u00a0this issue of Developmental Cell, Wang et\u00a0al. (2013) find that linc-RoR maintains human embryonic stem cell self-renewal by functioning as a sponge to trap miR-145, thus regulating core pluripotency factors Oct4, Nanog, and Sox2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597480", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1175, "text": "Enrichment of expressed lincRNA promoters in enhancer marks provides an additional argument for the involvement of lincRNAs in the regulation of transcription in cis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268656", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 938, "text": "Together, these findings suggest that lincRNA-p21 is an important player in the regulation of the Warburg effect and also implicate lincRNA-p21 as a valuable therapeutic target for cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24316222", "endSection": "abstract" }, { "offsetInBeginSection": 1387, "offsetInEndSection": 1675, "text": "Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24080187", "endSection": "abstract" }, { "offsetInBeginSection": 1252, "offsetInEndSection": 1466, "text": "Taken together, our results imply that mdig is involved in the regulation of H3K9me3 to influence the heterochromatin structure of the genome and the expression of genes important for cell growth or transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23965803", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 110, "text": "ndogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23541921", "endSection": "title" }, { "offsetInBeginSection": 386, "offsetInEndSection": 552, "text": "Here, we demonstrate that a lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23541921", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 848, "text": "We suggest that linc-RoR forms a feedback loop with core TFs and miRNAs to regulate ESC maintenance and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23541921", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 96, "text": "ammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841487", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 875, "text": "Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841487", "endSection": "abstract" } ] }, { "body": "Which is the protein encoded by the human gene GRIK?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24449200", "http://www.ncbi.nlm.nih.gov/pubmed/22291662" ], "ideal_answer": [ "Glutamate Receptor Ionotropic Kainate" ], "exact_answer": [ "glutamate receptor ionotropic kainate" ], "type": "factoid", "id": "56f6d11c09dd18d46b00000f", "snippets": [ { "offsetInBeginSection": 331, "offsetInEndSection": 377, "text": "GRIK\u2009=\u2009glutamate receptor, ionotropic, kainate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24449200", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 825, "text": " To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA) subunit variant and kainate (GRIK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22291662", "endSection": "abstract" } ] }, { "body": "Which residue of alpha-synuclein was found to be phosphorylated in Lewy bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22232559", "http://www.ncbi.nlm.nih.gov/pubmed/15834418", "http://www.ncbi.nlm.nih.gov/pubmed/18562315", "http://www.ncbi.nlm.nih.gov/pubmed/16847063", "http://www.ncbi.nlm.nih.gov/pubmed/11813001", "http://www.ncbi.nlm.nih.gov/pubmed/23314528", "http://www.ncbi.nlm.nih.gov/pubmed/23567651" ], "ideal_answer": [ "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson's disease patients where it mainly accumulates in the Lewy bodiesApproximately 90% of \u03b1-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129). In contrast, only 4% or less of total \u03b1-syn is phosphorylated at this residue in the normal brain. This suggests that the accumulation of Ser129-phosphorylated \u03b1-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease", "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies, which are characteristic pathologic lesions of Parkinson disease.", "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinsons disease patients where it mainly accumulates in the Lewy bodies", "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson s disease patients where it mainly accumulates in the Lewy bodies " ], "exact_answer": [ "Serine 129" ], "concepts": [ "http://www.uniprot.org/uniprot/SYUA_SERCA", "http://www.uniprot.org/uniprot/SYUA_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.uniprot.org/uniprot/SYUA_ERYPA", "http://www.uniprot.org/uniprot/SYUA_GORGO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016310", "http://www.uniprot.org/uniprot/SYUA_PANPA", "http://www.uniprot.org/uniprot/SYUA_ATEGE", "http://www.uniprot.org/uniprot/SYUA_RAT", "http://www.uniprot.org/uniprot/SYUA_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016631", "http://www.uniprot.org/uniprot/SYUA_MACMU" ], "type": "factoid", "id": "550c4011a103b78016000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson's disease patients where it mainly accumulates in the Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567651", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 649, "text": "Approximately 90% of \u03b1-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129). In contrast, only 4% or less of total \u03b1-syn is phosphorylated at this residue in the normal brain. This suggests that the accumulation of Ser129-phosphorylated \u03b1-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314528", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies. These inclusion bodies are the characteristic pathologic lesions of Parkinson disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15834418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15834418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "\ufffd-Synuclein is causative for autosomal dominant familial Parkinson disease and dementia with Lewy bodies, and the phosphorylation of \ufffd-synuclein at residue Ser-129 is a key posttranslational modification detected in Parkinson disease/dementia with Lewy bodies lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232559", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 939, "text": "Here, we show by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11813001", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 940, "text": "Here, we show by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11813001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "alpha-Synuclein is a major protein component deposited in Lewy bodies and Lewy neurites that is extensively phosphorylated at Ser(129), although its role in neuronal degeneration is still elusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18562315", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1802, "text": "These observations are most consistent with a model in which preferential accumulation of normally produced Ser-129 phosphorylated alpha-synuclein is the key event responsible for the formation of Lewy bodies in various Lewy body diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847063", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 406, "text": "The predominant modification of alpha-synuclein in Lewy bodies is a single phosphorylation at Ser-129.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847063", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 390, "text": "Approximately 90% of \u00ce\u00b1-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314528", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 655, "text": "This suggests that the accumulation of Ser129-phosphorylated \u00ce\u00b1-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314528", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 939, "text": "Here, we show by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11813001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15834418", "endSection": "abstract" } ] }, { "body": "Is paroxetine effective for treatment of premenstrual dysphoric disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16633152", "http://www.ncbi.nlm.nih.gov/pubmed/18517289", "http://www.ncbi.nlm.nih.gov/pubmed/12215058", "http://www.ncbi.nlm.nih.gov/pubmed/9463792", "http://www.ncbi.nlm.nih.gov/pubmed/8834412", "http://www.ncbi.nlm.nih.gov/pubmed/20175591", "http://www.ncbi.nlm.nih.gov/pubmed/17035933", "http://www.ncbi.nlm.nih.gov/pubmed/17286545", "http://www.ncbi.nlm.nih.gov/pubmed/15089103", "http://www.ncbi.nlm.nih.gov/pubmed/18983224", "http://www.ncbi.nlm.nih.gov/pubmed/18289149", "http://www.ncbi.nlm.nih.gov/pubmed/19803925", "http://www.ncbi.nlm.nih.gov/pubmed/12672169", "http://www.ncbi.nlm.nih.gov/pubmed/19370564", "http://www.ncbi.nlm.nih.gov/pubmed/11420571", "http://www.ncbi.nlm.nih.gov/pubmed/9213079", "http://www.ncbi.nlm.nih.gov/pubmed/11403977", "http://www.ncbi.nlm.nih.gov/pubmed/16098854", "http://www.ncbi.nlm.nih.gov/pubmed/11865558", "http://www.ncbi.nlm.nih.gov/pubmed/16259535", "http://www.ncbi.nlm.nih.gov/pubmed/15385695", "http://www.ncbi.nlm.nih.gov/pubmed/15841196", "http://www.ncbi.nlm.nih.gov/pubmed/18559957", "http://www.ncbi.nlm.nih.gov/pubmed/15139800", "http://www.ncbi.nlm.nih.gov/pubmed/19724771" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugbank/pharmacology", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00715", "o": "Paroxetine, an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type, has no active metabolites and has the highest specificity for serotonin receptors of all the SSRIs. It is used to treat depression resistant to other antidepressants, depression complicated by anxiety, panic disorder, social and general anxiety disorder, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder, premature ejaculation, and hot flashes of menopause in women with breast cancer." } ], "ideal_answer": [ "Yes, paroxetine is effective and FDA approved treatment of women with premenstrual dysphoric disorder. A number of well designed clinical trials have confirmed efficacy and safety of both continuous or intermittent regiments of paroxetine for treatment of premenstrual dysphoric disorder. A number of other antidepressants and hormaonal therapies were also shown to be effective and are FDA approved for treatment of women with premenstrual dysphoric disorder." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017374", "http://www.biosemantics.org/jochem#4272785", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011293" ], "type": "yesno", "id": "514a59c2d24251bc0500005d", "snippets": [ { "offsetInBeginSection": 360, "offsetInEndSection": 548, "text": "To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20175591", "endSection": "sections.0" }, { "offsetInBeginSection": 2379, "offsetInEndSection": 2518, "text": "All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19370564", "endSection": "sections.0" }, { "offsetInBeginSection": 230, "offsetInEndSection": 593, "text": "Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18983224", "endSection": "sections.0" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1174, "text": "Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18559957", "endSection": "sections.0" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1641, "text": "When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18517289", "endSection": "sections.0" }, { "offsetInBeginSection": 1655, "offsetInEndSection": 1769, "text": "Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18517289", "endSection": "sections.0" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1323, "text": "All these women had significant improvements in the HAMA, HAMD, CGI, and PRISM calendar. The rate of response to paroxetine treatment lay between 50% and 78.6% in the continuous-treatment group, and 37.5-93.8% in the intermittent-treatment group, as determined at the study end-point.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18289149", "endSection": "sections.0" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1672, "text": "The present results indicate that paroxetine is effective in both continuous and intermittent treatment of oriental PMDD women, and that the effects of active treatment lasted for six consecutive treatment menstrual cycles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18289149", "endSection": "sections.0" }, { "offsetInBeginSection": 609, "offsetInEndSection": 760, "text": "Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17286545", "endSection": "sections.0" }, { "offsetInBeginSection": 886, "offsetInEndSection": 993, "text": "Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035933", "endSection": "sections.0" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1278, "text": "Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035933", "endSection": "sections.0" }, { "offsetInBeginSection": 819, "offsetInEndSection": 991, "text": "Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16633152", "endSection": "sections.0" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1222, "text": "However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16633152", "endSection": "sections.0" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1404, "text": "Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16633152", "endSection": "sections.0" }, { "offsetInBeginSection": 596, "offsetInEndSection": 732, "text": "The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19803925", "endSection": "sections.0" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1053, "text": "Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16098854", "endSection": "sections.0" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1196, "text": "For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16098854", "endSection": "sections.0" }, { "offsetInBeginSection": 595, "offsetInEndSection": 904, "text": "A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15841196", "endSection": "sections.0" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1063, "text": "Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15841196", "endSection": "sections.0" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1313, "text": "At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15385695", "endSection": "sections.0" }, { "offsetInBeginSection": 1631, "offsetInEndSection": 1749, "text": "Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15385695", "endSection": "sections.0" }, { "offsetInBeginSection": 483, "offsetInEndSection": 658, "text": "Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15139800", "endSection": "sections.0" }, { "offsetInBeginSection": 225, "offsetInEndSection": 759, "text": "In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD]).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15089103", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12672169", "endSection": "sections.0" }, { "offsetInBeginSection": 4127, "offsetInEndSection": 4477, "text": "Studies having compared the efficiency of antidepressants according to their serotonin activity (paroxetine or sertraline versus maprotiline, that is a selective noradrenaline re-uptake inhibitor), showed that serotonin re-uptake inhibitors were significantly more efficient on all symptoms than maprotiline, that was not more efficient than placebo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11865558", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11420571", "endSection": "sections.0" }, { "offsetInBeginSection": 1469, "offsetInEndSection": 1612, "text": "Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9463792", "endSection": "sections.0" }, { "offsetInBeginSection": 822, "offsetInEndSection": 1137, "text": "The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8834412", "endSection": "sections.0" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1614, "text": "The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8834412", "endSection": "sections.0" }, { "offsetInBeginSection": 1615, "offsetInEndSection": 1745, "text": "These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8834412", "endSection": "sections.0" }, { "offsetInBeginSection": 312, "offsetInEndSection": 563, "text": "The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9213079", "endSection": "sections.0" } ] }, { "body": "What is known about thalidomide therapy and survival of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10673511", "http://www.ncbi.nlm.nih.gov/pubmed/15817350", "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "http://www.ncbi.nlm.nih.gov/pubmed/18403492", "http://www.ncbi.nlm.nih.gov/pubmed/16053669", "http://www.ncbi.nlm.nih.gov/pubmed/22086614", "http://www.ncbi.nlm.nih.gov/pubmed/11763420", "http://www.ncbi.nlm.nih.gov/pubmed/20729242", "http://www.ncbi.nlm.nih.gov/pubmed/18661102", "http://www.ncbi.nlm.nih.gov/pubmed/15380566", "http://www.ncbi.nlm.nih.gov/pubmed/17031553", "http://www.ncbi.nlm.nih.gov/pubmed/14654909", "http://www.ncbi.nlm.nih.gov/pubmed/15072467", "http://www.ncbi.nlm.nih.gov/pubmed/25427949", "http://www.ncbi.nlm.nih.gov/pubmed/17031561", "http://www.ncbi.nlm.nih.gov/pubmed/21896554", "http://www.ncbi.nlm.nih.gov/pubmed/18314417", "http://www.ncbi.nlm.nih.gov/pubmed/17465245" ], "ideal_answer": [ "Findings regarding clinical value of thalidomide in terms of survival in patients with glioblastoma remain mixed. It has been shown that thalidomide can improve survival of recurrent glioblastoma patients. However, other authors have not confirmed these findings. Furthermore, thalidomide did not improve survival of newly diagnosed glioblastoma and pediatric glioblastoma patients." ], "concepts": [ "http://www.biosemantics.org/jochem#4250023", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013792" ], "type": "summary", "id": "54f1e887c409818c32000004", "snippets": [ { "offsetInBeginSection": 1098, "offsetInEndSection": 1254, "text": "In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 296, "text": "The authors previously reported improved outcome in patients with recurrent glioblastoma treated with thalidomide and irinotecan compared with historical controls. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086614", "endSection": "abstract" }, { "offsetInBeginSection": 1546, "offsetInEndSection": 1746, "text": "CONCLUSIONS: The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against AG, although a subset of patients experienced prolonged PFS/OS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086614", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1402, "text": "The treatment regimen was well tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotinib and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896554", "endSection": "abstract" }, { "offsetInBeginSection": 1592, "offsetInEndSection": 1769, "text": "The addition of celecoxib and thalidomide to adjuvant temozolomide was well tolerated but did not meet the primary end point of improvement of 4-month PFS from study enrollment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18403492", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1642, "text": "CONCLUSION: The combination of irinotecan and thalidomide has limited activity against GBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18661102", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1401, "text": "The combination of irinotecan, a cytotoxic agent, and thalidomide, an antiangiogenic agent, shows promising activity against recurrent GBM in patients not receiving EIACs and warrants further study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18314417", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 1015, "text": "CONCLUSION: The administration of temozolomide in association with thalidomide after radiotherapy (RT) does not offer an advantage over temozolomide alone in adults with newly diagnosed GBM. The two therapeutic strategies produce similar results for survival, but the latter regimen shows a moderate increase in toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17465245", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1734, "text": "CONCLUSION: This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17031561", "endSection": "abstract" }, { "offsetInBeginSection": 2100, "offsetInEndSection": 2257, "text": "In this small patient sample adding thalidomide to radiation did not improve TTP or TTD from historical controls, however, toxicity appeared to be increased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17031553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Experimental studies have demonstrated that thalidomide has anti-tumor activity mediated by blockage of angiogenesis, with clinical efficacy in multiple myeloma, glioblastoma multiforme, and renal cell cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16053669", "endSection": "abstract" }, { "offsetInBeginSection": 905, "offsetInEndSection": 1159, "text": "CONCLUSIONS: The combined therapy was relatively well tolerated, but there was no survival advantage compared with historical studies using XRT either with adjuvant nitrosourea chemotherapy, with TMZ alone, or with the combination of TMZ and thalidomide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15817350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "PURPOSE: The chemotherapeutic agent temozolomide (TMZ) and the antiangiogenic agent thalidomide have both demonstrated antitumor activity in patients with recurrent malignant glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15380566", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1470, "text": "CONCLUSIONS: This strategy of combination TMZ, thalid and RT was relatively well tolerated with favorable survival outcome for patients with GM when compared to patients not treated with adjuvant chemotherapy and similar to those who have received nitrosourea adjuvant chemotherapy. It is unclear the added advantage thalid has in combination with TMZ for this patient population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15380566", "endSection": "abstract" }, { "offsetInBeginSection": 1937, "offsetInEndSection": 2193, "text": "CONCLUSIONS: The combination of thalidomide and temozolomide in the treatment of GBM appears to be more effective than that of thalidomide alone with respect to survival, TTP, and neuroradiological documentation of progression, stable disease or response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15072467", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1306, "text": "In conclusion, thalidomide induces modest side effects and it may be considered a valid therapeutic option for patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14654909", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1399, "text": "Thalidomide is a well-tolerated drug that may have some activity in the treatment of recurrent glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11763420", "endSection": "abstract" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1637, "text": "Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10673511", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1231, "text": " In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Thalidomide prolongs disease stabilization after conventional therapy in patients with recurrent glioblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14654909", "endSection": "title" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1276, "text": "In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1246, "text": "No patients completed the planned 12 months of thalidomide therapy and all have since died of disease progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17031553", "endSection": "abstract" } ] }, { "body": "Is endostatin a proangiogenic factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11301401", "http://www.ncbi.nlm.nih.gov/pubmed/17191085", "http://www.ncbi.nlm.nih.gov/pubmed/12516034", "http://www.ncbi.nlm.nih.gov/pubmed/12525513", "http://www.ncbi.nlm.nih.gov/pubmed/15023336", "http://www.ncbi.nlm.nih.gov/pubmed/20926012", "http://www.ncbi.nlm.nih.gov/pubmed/18316578", "http://www.ncbi.nlm.nih.gov/pubmed/20739545", "http://www.ncbi.nlm.nih.gov/pubmed/15985216", "http://www.ncbi.nlm.nih.gov/pubmed/23788612", "http://www.ncbi.nlm.nih.gov/pubmed/12857600", "http://www.ncbi.nlm.nih.gov/pubmed/15901832", "http://www.ncbi.nlm.nih.gov/pubmed/12209972", "http://www.ncbi.nlm.nih.gov/pubmed/12209593", "http://www.ncbi.nlm.nih.gov/pubmed/18838410", "http://www.ncbi.nlm.nih.gov/pubmed/17471348", "http://www.ncbi.nlm.nih.gov/pubmed/10599057", "http://www.ncbi.nlm.nih.gov/pubmed/21442281", "http://www.ncbi.nlm.nih.gov/pubmed/17950364", "http://www.ncbi.nlm.nih.gov/pubmed/17003465", "http://www.ncbi.nlm.nih.gov/pubmed/21181203", "http://www.ncbi.nlm.nih.gov/pubmed/17475706", "http://www.ncbi.nlm.nih.gov/pubmed/22212932", "http://www.ncbi.nlm.nih.gov/pubmed/9887458", "http://www.ncbi.nlm.nih.gov/pubmed/11400342", "http://www.ncbi.nlm.nih.gov/pubmed/18483373", "http://www.ncbi.nlm.nih.gov/pubmed/19336373", "http://www.ncbi.nlm.nih.gov/pubmed/10835101", "http://www.ncbi.nlm.nih.gov/pubmed/20594164", "http://www.ncbi.nlm.nih.gov/pubmed/15939343", "http://www.ncbi.nlm.nih.gov/pubmed/21330475", "http://www.ncbi.nlm.nih.gov/pubmed/15739185", "http://www.ncbi.nlm.nih.gov/pubmed/15931265", "http://www.ncbi.nlm.nih.gov/pubmed/14614021", "http://www.ncbi.nlm.nih.gov/pubmed/15831230" ], "ideal_answer": [ "No, endostatin is an antiangiogenic factor" ], "exact_answer": "no", "concepts": [ "http://www.uniprot.org/uniprot/COFA1_MOUSE", "http://www.uniprot.org/uniprot/COIA1_MOUSE", "http://www.uniprot.org/uniprot/COFA1_HUMAN", "http://www.uniprot.org/uniprot/COIA1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043169" ], "type": "yesno", "id": "53124e84e3eabad02100000c", "snippets": [ { "offsetInBeginSection": 536, "offsetInEndSection": 569, "text": "endostatin (antiangiogenic factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788612", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 423, "text": "antiangiogenic factors include thrombospondin-1, angiostatin, and endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22212932", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 80, "text": " human endostatin (rh-endostatin), a potential antiangiogenic agent, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21442281", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 214, "text": "antiangiogenic PF4 and endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330475", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 106, "text": "Angiostatin and endostatin are endogenous inhibitors of angiogenesis with anticancer effects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21181203", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 544, "text": "the antiangiogenic factors, cystatin C and endostatin, were measured", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20926012", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 696, "text": "accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20739545", "endSection": "abstract" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1549, "text": "antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20594164", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 60, "text": "Endostatin is an antiangiogenic growth factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336373", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 184, "text": "angiogenesis inhibitor endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18838410", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 183, "text": "Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483373", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 130, "text": "Thrombospondin-1 (Tsp1), endostatin, and tumstatin are extracellular matrix-associated proteins that inhibit angiogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18316578", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 542, "text": "specific inhibitors of angiogenesis such as platelet factor, angiostatin, endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17950364", "endSection": "abstract" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1468, "text": "endostatin, an endogenous inhibitor of angiogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17475706", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 486, "text": "antiangiogenic factors (pigment epithelium-derived factor [PEDF]; angiostatin; restin; and endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17471348", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 434, "text": "endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17191085", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 245, "text": "endogenous angiogenesis inhibitors endostatin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17003465", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 66, "text": "ndostatin is a potent inhibitor of angiogenesis and tumor growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15985216", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1157, "text": "endogenous angiogenesis inhibitor - endostatin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15939343", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 317, "text": "Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15931265", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 956, "text": "antiangiogenic protein endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15901832", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 556, "text": "A number of endogenous inhibitors of angiogenesis are found in the body. Some of these are synthesized by specific cells in different organs, and others are created by extracellular proteolytic cleavage of plasma-derived or extracellular matrix-localized proteins. In this review, we focus on angiostatin, endostatin,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831230", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 552, "text": "endostatin (a direct inhibitor of angiogenesis) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15739185", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 308, "text": "endogenous angiogenesis inhibitor endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15023336", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 136, "text": "Endostatin, a peptide derived from proteolysis of collagen XVIII, is an endogenous inhibitor of angiogenesis and tumor growth. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14614021", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 182, "text": "anti-angiogenic factor endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12857600", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 91, "text": "Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525513", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 972, "text": "angiogenic inhibitors such as endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12516034", "endSection": "abstract" }, { "offsetInBeginSection": 1779, "offsetInEndSection": 1820, "text": "endostatin inhibits the angiogenic switch", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12209972", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 802, "text": "antiangiogenic endostatin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12209593", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 709, "text": "direct acting antiangiogenic agents (e.g., endostatin) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11400342", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 238, "text": "Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301401", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 532, "text": "specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10835101", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 804, "text": "Endostatin, which is a natural inhibitor of angiogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10599057", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 985, "text": "Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9887458", "endSection": "abstract" } ] }, { "body": "List Genes associated with adolescent idiopathic scoliosis", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17632395", "http://www.ncbi.nlm.nih.gov/pubmed/11136708", "http://www.ncbi.nlm.nih.gov/pubmed/11343318", "http://www.ncbi.nlm.nih.gov/pubmed/12384783", "http://www.ncbi.nlm.nih.gov/pubmed/20543391", "http://www.ncbi.nlm.nih.gov/pubmed/23591653", "http://www.ncbi.nlm.nih.gov/pubmed/22615788", "http://www.ncbi.nlm.nih.gov/pubmed/24551838", "http://www.ncbi.nlm.nih.gov/pubmed/25401082", "http://www.ncbi.nlm.nih.gov/pubmed/16540873", "http://www.ncbi.nlm.nih.gov/pubmed/21983728", "http://www.ncbi.nlm.nih.gov/pubmed/17108412", "http://www.ncbi.nlm.nih.gov/pubmed/22009847", "http://www.ncbi.nlm.nih.gov/pubmed/22002330", "http://www.ncbi.nlm.nih.gov/pubmed/18001530", "http://www.ncbi.nlm.nih.gov/pubmed/18386809", "http://www.ncbi.nlm.nih.gov/pubmed/22992817", "http://www.ncbi.nlm.nih.gov/pubmed/21192222", "http://www.ncbi.nlm.nih.gov/pubmed/21216876", "http://www.ncbi.nlm.nih.gov/pubmed/17534191", "http://www.ncbi.nlm.nih.gov/pubmed/22744455", "http://www.ncbi.nlm.nih.gov/pubmed/22193623", "http://www.ncbi.nlm.nih.gov/pubmed/17785083", "http://www.ncbi.nlm.nih.gov/pubmed/18007247", "http://www.ncbi.nlm.nih.gov/pubmed/25283277", "http://www.ncbi.nlm.nih.gov/pubmed/23453657", "http://www.ncbi.nlm.nih.gov/pubmed/15303021", "http://www.ncbi.nlm.nih.gov/pubmed/23467837", "http://www.ncbi.nlm.nih.gov/pubmed/23038618", "http://www.ncbi.nlm.nih.gov/pubmed/10494097", "http://www.ncbi.nlm.nih.gov/pubmed/19139660", "http://www.ncbi.nlm.nih.gov/pubmed/19212754", "http://www.ncbi.nlm.nih.gov/pubmed/24603539", "http://www.ncbi.nlm.nih.gov/pubmed/17023856", "http://www.ncbi.nlm.nih.gov/pubmed/8180508", "http://www.ncbi.nlm.nih.gov/pubmed/21146321", "http://www.ncbi.nlm.nih.gov/pubmed/19634821", "http://www.ncbi.nlm.nih.gov/pubmed/22278929", "http://www.ncbi.nlm.nih.gov/pubmed/21520258", "http://www.ncbi.nlm.nih.gov/pubmed/25313366", "http://www.ncbi.nlm.nih.gov/pubmed/1345899", "http://www.ncbi.nlm.nih.gov/pubmed/12973153", "http://www.ncbi.nlm.nih.gov/pubmed/15832907", "http://www.ncbi.nlm.nih.gov/pubmed/15457700", "http://www.ncbi.nlm.nih.gov/pubmed/15457701", "http://www.ncbi.nlm.nih.gov/pubmed/25504735", "http://www.ncbi.nlm.nih.gov/pubmed/19340878", "http://www.ncbi.nlm.nih.gov/pubmed/18021699", "http://www.ncbi.nlm.nih.gov/pubmed/24833718", "http://www.ncbi.nlm.nih.gov/pubmed/21308753", "http://www.ncbi.nlm.nih.gov/pubmed/21228746", "http://www.ncbi.nlm.nih.gov/pubmed/19337134", "http://www.ncbi.nlm.nih.gov/pubmed/20627007", "http://www.ncbi.nlm.nih.gov/pubmed/17414906", "http://www.ncbi.nlm.nih.gov/pubmed/15088139", "http://www.ncbi.nlm.nih.gov/pubmed/21691901", "http://www.ncbi.nlm.nih.gov/pubmed/2605936", "http://www.ncbi.nlm.nih.gov/pubmed/20733416", "http://www.ncbi.nlm.nih.gov/pubmed/19192405", "http://www.ncbi.nlm.nih.gov/pubmed/9408396", "http://www.ncbi.nlm.nih.gov/pubmed/21228692", "http://www.ncbi.nlm.nih.gov/pubmed/24469715", "http://www.ncbi.nlm.nih.gov/pubmed/10096591", "http://www.ncbi.nlm.nih.gov/pubmed/24038971", "http://www.ncbi.nlm.nih.gov/pubmed/23096252", "http://www.ncbi.nlm.nih.gov/pubmed/20436380", "http://www.ncbi.nlm.nih.gov/pubmed/22158057", "http://www.ncbi.nlm.nih.gov/pubmed/18794762", "http://www.ncbi.nlm.nih.gov/pubmed/17108395", "http://www.ncbi.nlm.nih.gov/pubmed/17108398", "http://www.ncbi.nlm.nih.gov/pubmed/8982144", "http://www.ncbi.nlm.nih.gov/pubmed/25408124", "http://www.ncbi.nlm.nih.gov/pubmed/2932368", "http://www.ncbi.nlm.nih.gov/pubmed/23259508", "http://www.ncbi.nlm.nih.gov/pubmed/23364988", "http://www.ncbi.nlm.nih.gov/pubmed/22095884", "http://www.ncbi.nlm.nih.gov/pubmed/23812140", "http://www.ncbi.nlm.nih.gov/pubmed/18985072", "http://www.ncbi.nlm.nih.gov/pubmed/23724359", "http://www.ncbi.nlm.nih.gov/pubmed/24023777", "http://www.ncbi.nlm.nih.gov/pubmed/17932119", "http://www.ncbi.nlm.nih.gov/pubmed/19726741", "http://www.ncbi.nlm.nih.gov/pubmed/15717203", "http://www.ncbi.nlm.nih.gov/pubmed/19080622", "http://www.ncbi.nlm.nih.gov/pubmed/17108457", "http://www.ncbi.nlm.nih.gov/pubmed/21740577", "http://www.ncbi.nlm.nih.gov/pubmed/22183150", "http://www.ncbi.nlm.nih.gov/pubmed/17156628", "http://www.ncbi.nlm.nih.gov/pubmed/25005481", "http://www.ncbi.nlm.nih.gov/pubmed/25410117", "http://www.ncbi.nlm.nih.gov/pubmed/10399127", "http://www.ncbi.nlm.nih.gov/pubmed/10466862" ], "ideal_answer": [ "Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis.Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.", "No genetic associations have yet been found to adolescent idiopathic scoliosis." ], "exact_answer": [ [ "no associations found yet" ] ], "type": "list", "id": "54d670163706e8952800000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25504735", "endSection": "title" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1329, "text": "Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25283277", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1299, "text": "HL1 is of interest, as it encodes an axon guidance protein related to Robo3. Mutations in the Robo3 protein cause horizontal gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Other top associations in our GWAS were with SNPs in the DSCAM gene encoding an axon guidance protein in the same structural class with Chl1 and Robo3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21216876", "endSection": "abstract" } ] }, { "body": "Can botulism poisoning of a pregnant woman harm her fetus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23735780", "http://www.ncbi.nlm.nih.gov/pubmed/24235190" ], "ideal_answer": [ "Botulinum toxin, which causes botulism, is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, botulinum toxin has a high molecular weight, and does not appear to cross the placenta. Based on the study cases reported in the literature, botulism poisoning during pregnancy does not appear to increase the risk of adverse outcome in the fetus." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11976", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005333", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014930", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011042", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011041", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037841" ], "type": "yesno", "id": "554763f0f35db75526000002", "snippets": [ { "offsetInBeginSection": 632, "offsetInEndSection": 871, "text": "Two botulism outbreaks were attributed to commercial ready-to-eat meat products and 3 to foods served in restaurants; several cases were attributed to non-Native home-prepared foods. Three affected pregnant women delivered healthy infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23735780", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 610, "text": "Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24235190", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 593, "text": "From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24235190", "endSection": "abstract" } ] }, { "body": "List the off-label use of SSRIs", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22473248", "http://www.ncbi.nlm.nih.gov/pubmed/16310120", "http://www.ncbi.nlm.nih.gov/pubmed/22136212", "http://www.ncbi.nlm.nih.gov/pubmed/20235039", "http://www.ncbi.nlm.nih.gov/pubmed/15062207", "http://www.ncbi.nlm.nih.gov/pubmed/18330528", "http://www.ncbi.nlm.nih.gov/pubmed/18371047", "http://www.ncbi.nlm.nih.gov/pubmed/21176430", "http://www.ncbi.nlm.nih.gov/pubmed/22712761", "http://www.ncbi.nlm.nih.gov/pubmed/23093633", "http://www.ncbi.nlm.nih.gov/pubmed/15928960", "http://www.ncbi.nlm.nih.gov/pubmed/23425613", "http://www.ncbi.nlm.nih.gov/pubmed/18360636", "http://www.ncbi.nlm.nih.gov/pubmed/22760463", "http://www.ncbi.nlm.nih.gov/pubmed/21077473", "http://www.ncbi.nlm.nih.gov/pubmed/21601255", "http://www.ncbi.nlm.nih.gov/pubmed/16481094", "http://www.ncbi.nlm.nih.gov/pubmed/15291651", "http://www.ncbi.nlm.nih.gov/pubmed/15643101" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/55601", "o": "Use within normal clinical practice" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/55601", "o": "Intervention #55601 (Drug:SSRIs)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/55601", "o": "SSRIs" } ], "ideal_answer": [ "depression during childhood and adolescence\nPremature ejaculation (PE)\nerectile dysfunction\nInsomnia\npostprostatectomy established stress urinary incontinence.\nmood and anxiety disorders during pregnancy and breast feeding\nsymptoms of vasomotor dysregulation (hot flashes) associated with the menopausal transition and sex hormone deprivation\n..off-label uses include the treatment of bulimia, benzodiazepine/alcohol dependence, fibromyalgia, central nervous system degenerative diseases (behavioral disorders in dementia and other organic disorders), schizophrenia, chronic pain disease and diabetic neuropathy, sexual dysfunction." ], "exact_answer": [ [ "depression during childhood and adolescence" ], [ "Premature ejaculation", "PE" ], [ "erectile dysfunction" ], [ "Insomnia" ], [ "postprostatectomy established stress urinary incontinence", "SUI" ], [ "mood and anxiety disorders during pregnancy and breast feeding" ], [ "hot flashes", "postmenopausal symptoms" ], [ "bulimia" ], [ "benzodiazepine/alcohol dependence" ], [ "fibromyalgia" ], [ "behavioral disorders in dementia" ], [ "schizophrenia" ], [ "chronic pain disease" ], [ "diabetic neuropathy" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056687" ], "type": "list", "id": "5324cf139b2d7acc7e00001f", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 138, "text": "The present analysis evaluates the prevalence and medication use in inpatients with depression during childhood and adolescence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23425613", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1478, "text": "Fluoxetine and mirtazapine were the most frequently prescribed substances. Sertraline, escitalopram, and citalopram were also prescribed. CONCLUSION: A reserved medical treatment can be observed in child and adolescence psychiatry. Off-label use seems to be nearly unavoidable due to the lack of newly authorized medicine. Moreover, the numerous prescriptions for fluoxetine, the only SSRI currently approved for this age group in Germany, lead to the question of possible unauthorized alternatives.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23425613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Premature ejaculation (PE) is a common sexual dysfunction affecting 20% to 30% of men worldwide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23093633", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 654, "text": "Treatment of PE typically involves pharmacotherapy, particularly when lifelong. Although there are numerous reports on the off-label use of selective serotonin reuptake inhibitors (SSRIs) and other compounds, only 2 treatments have been evaluated in randomized controlled phase 3 clinical trials: PSD502 and dapoxetine (SSRI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23093633", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 88, "text": "Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22760463", "endSection": "title" }, { "offsetInBeginSection": 1526, "offsetInEndSection": 1744, "text": "Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended. Off-label use of duloxetine and pregabalin can be considered in case of no comorbid mental disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22760463", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 617, "text": "Trazodone is an antidepressant belonging to the class of serotonin receptor antagonists and reuptake inhibitors. It is approved by the FDA for the treatment of depression. Insomnia is the most frequent reason for prescription of trazodone. It has also been proven useful in the treatment of anxiety disorders. Other off-label uses include the treatment of bulimia, benzodiazepine/alcohol dependence, fibromyalgia, central nervous system degenerative diseases (behavioral disorders in dementia and other organic disorders), schizophrenia, chronic pain disease and diabetic neuropathy, sexual dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22712761", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 405, "text": "symptoms of vasomotor dysregulation (hot flashes) associated with the menopausal transition and sex hormone deprivation. Implication of changes in central neurotransmission in the pathogenesis of hot flashes has prompted the off-label use of serotonergic and \u03b3-aminobutyric acid-ergic drugs as a therapeutic alternative,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473248", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 1052, "text": "Sertraline was the most prescribed antidepressant for the treatment of major depressive disorder, followed by fluvoxamine and tianeptine. Fluvoxamine was the most prescribed antidepressant for the treatment of anxiety disorders and mixed disorders of emotions and conduct. Off-label prescribing of antidepressants was found in 85.6% of young patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136212", "endSection": "abstract" }, { "offsetInBeginSection": 1653, "offsetInEndSection": 1786, "text": "Our results suggest that duloxetine is a possible alternative treatment of postprostatectomy established stress urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21601255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Pharmacological treatment of fibromyalgia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21176430", "endSection": "title" }, { "offsetInBeginSection": 664, "offsetInEndSection": 838, "text": "different classes of drugs with different mechanisms of action are used off-label, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21176430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 473, "text": "Gynaecological cancer patients generally suffer from an earlier and more severe menopausal syndrome than the general female population. Hormone replacement therapy is often contraindicated and there are non-hormonal treatments that are proven to be more effective than placebo in randomized controlled trials, e.g., some antidepressants, gabapentine and clonidine. The main limits to the use of these drugs in controlling hot flashes are the off-label use for this purpose,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21077473", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 150, "text": "ymptomatic therapy for patients with erectile dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20235039", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1073, "text": "a oral daily off label use therapy with selective serotonin re-uptake inhibitors (paroxetine, fluoxetine, sertraline) can be offered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20235039", "endSection": "abstract" }, { "offsetInBeginSection": 1547, "offsetInEndSection": 1668, "text": "Without the Food and Drug Administration approval, dapoxetine, as well as other SSRIs in PE, is an off-label drug for PE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371047", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 512, "text": "the treatment of PE consists of primarily off-label use of oral selective serotonin reuptake inhibitors (SSRIs) via either on-demand or daily delivery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18360636", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 961, "text": "The results of this off-label use show that Duloxetine is effective in men with SUI after prostate surgery even if standard pelvic floor exercises have failed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18330528", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Preliminary results on the off-label use of duloxetine for the treatment of stress incontinence after radical prostatectomy or cystectomy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16481094", "endSection": "title" }, { "offsetInBeginSection": 1536, "offsetInEndSection": 1972, "text": "the number of children and adolescents whose visits involved prescription of antidepressants, particularly SSRIs, has increased markedly through 2002. Although fluoxetine remained the most commonly prescribed, other SSRIs were increasingly prescribed through 2002. These trends raise concerns regarding the widespread off-label use of antidepressants lacking reliable evidence of safety and efficacy for use in children and adolescents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16310120", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 732, "text": "Given the presumed efficacy of these new compounds and the off-label use of the current SSRIs, one might conclude that psychotherapy\\behavior therapy for rapid ejaculation is an obsolete and antiquated intervention", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15928960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The use of selective serotonin reuptake inhibitors during pregnancy and breast-feeding:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15643101", "endSection": "title" }, { "offsetInBeginSection": 171, "offsetInEndSection": 618, "text": "The use of selective serotonin reuptake inhibitors during pregnancy or lactation is, to date, not promoted because of lack of safety documentation. However, the off-label use of these drugs has been common for several years. In the treatment of mood and anxiety disorders during pregnancy, the serotonin reuptake inhibitors are often preferred over tricyclic antidepressants because of their relatively few adverse effects and safety in overdose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15643101", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 224, "text": "The last few years have seen a remarkable rise in the off-label use of trazodone for inducing sleep in nondepressed patients, to a degree that it is prescribed for this purpose as commonly as the leading hypnotic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15291651", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 693, "text": "Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15062207", "endSection": "abstract" } ] }, { "body": "Which is the definition of pyknons in DNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16636294", "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "http://www.ncbi.nlm.nih.gov/pubmed/19833446", "http://www.ncbi.nlm.nih.gov/pubmed/16751093", "http://www.ncbi.nlm.nih.gov/pubmed/19229130", "http://www.ncbi.nlm.nih.gov/pubmed/19052667" ], "ideal_answer": [ "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA, which have additional nonoverlapping instances in the untranslated and protein-coding regions. They are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009711" ], "type": "summary", "id": "52e204a998d0239505000012", "snippets": [ { "offsetInBeginSection": 234, "offsetInEndSection": 472, "text": "Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16636294", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 231, "text": "a nonrandom pattern of repeated elements, called pyknons, which are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751093", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 551, "text": "We discuss the general implications of molecular epigenetics with special emphasis on drug abuse, bar-codes, pyknons, and miRNAs for translational and clinical research", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19052667", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 394, "text": "Here we report identification of ubiquitous template design sequences (templum intentio series, templints) of human genomes common for disease-associated SNPs, microRNAs and pyknons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19229130", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 604, "text": "We demonstrate that genome-unique SNP-coding sequences associated with multiple common human disorders appear assembled from series of ubiquitous short octamer sequences shared by 5'-UTR pyknons and microRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19229130", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1225, "text": "Allele-specific sequence variations link disease-associated SNPs to distinct sets of pyknons and microRNAs, suggesting that increased susceptibility to multiple common human disorders is associated with global alterations of genome-wide regulatory templates affecting the biogenesis and functions of non-coding RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19229130", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 147, "text": "yknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 417, "text": "Pyknons have only been discovered in the human genome, so it is unknown whether pyknons have wider biological relevance or are simply a phenomenon of the human genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 951, "text": "A. thaliana pyknons exhibit features similar to human pyknons, including being distinct sequence patterns, having multiple instances in genes and having remarkable similarity to small RNA sequences with roles in gene silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1090, "text": "Chromosomal position mapping revealed that genomic pyknon density has concordance with siRNA and transposable element positioning density", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1335, "text": "Because the A. thaliana and human genomes have approximately the same number of genes but drastically different amounts of non-coding DNA, these data reveal that pyknons represent a biologically important link between coding and non-coding DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1559, "text": "Because of the association of pyknons with siRNAs and localization to silenced regions of heterochromatin, we postulate that RNA-mediated gene silencing leads to the accumulation of gene sequences in non-coding DNA regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 1624, "offsetInEndSection": 1834, "text": " The new GSCKs are produced by evolutionary consolidation of retro-transcripts into pyknons that collect and evolve at the end of the pericentromeric heterochromatin and are eventually incorporated into the MDP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19833446", "endSection": "abstract" } ] }, { "body": "Does a linker histone exist in the yeast genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22586276", "http://www.ncbi.nlm.nih.gov/pubmed/9516420", "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "http://www.ncbi.nlm.nih.gov/pubmed/15046982", "http://www.ncbi.nlm.nih.gov/pubmed/11471242", "http://www.ncbi.nlm.nih.gov/pubmed/18687885", "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "http://www.ncbi.nlm.nih.gov/pubmed/16342967", "http://www.ncbi.nlm.nih.gov/pubmed/11574687", "http://www.ncbi.nlm.nih.gov/pubmed/24023978", "http://www.ncbi.nlm.nih.gov/pubmed/15050829" ], "ideal_answer": [ "Here, we present our results showing a connection between the linker histones, the higher-order chromatin structures, and the process of chronological lifespan of yeast cells. Characteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type. These results suggest that HHO1p may play a similar role to linker histones, but at restricted locations in the chromatin. The binding was structure specific, since the use of double-stranded DNA, or a mutant Hho1p in which the second DNA binding site of globular domain 1 was abolished, resulted in a significant decrease in bridged binding.", "Hho1p is a bona fide linker histone", "In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1. The putative linker histone in Saccharomyces cerevisiae, Hho1p, has two regions of sequence (GI and GII) that are homologous to the single globular domains of linker histones H1 and H5 in higher eukaryotes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015003", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012441", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.biosemantics.org/jochem#4278518", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4278518", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657" ], "type": "yesno", "id": "5709152ecf1c325851000014", "snippets": [ { "offsetInBeginSection": 999, "offsetInEndSection": 1034, "text": "Hho1p is a bona fide linker histone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9516420", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 248, "text": "In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11574687", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1089, "text": "HHO1p may play a similar role to linker histones, but at restricted locations in the chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11574687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The putative linker histone in Saccharomyces cerevisiae, Hho1p, has two regions of sequence (GI and GII) that are homologous to the single globular domains of linker histones H1 and H5 in higher eukaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15046982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The Saccharomyces cerevisiae homologue of the linker histone H1, Hho1p, has two domains that are similar in sequence to the globular domain of H1 (and variants such as H5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15050829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Two homologous domains of similar structure but different stability in the yeast linker histone, Hho1p", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15050829", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Saccharomyces cerevisiae encodes a single linker histone, Hho1p, with two globular domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16342967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The Saccharomyces cerevisiae linker histone Hho1p, with two globular domains, can simultaneously bind to two four-way junction DNA molecules", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16342967", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 272, "text": "Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687885", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Saccharomyces cerevisiae linker histone Hho1p is not essential for cell viability, and very little is known about its function in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Saccharomyces cerevisiae linker histone Hho1p functionally interacts with core histone H4 and negatively regulates the establishment of transcriptionally silent chromatin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "endSection": "title" }, { "offsetInBeginSection": 813, "offsetInEndSection": 1133, "text": " Unlike canonical linker histones in higher eukaryotes that have a single conserved globular domain, Hho1p possesses two globular domains. We show that the carboxyl-terminal globular domain of Hho1p is dispensable for its function, suggesting that the mode of Hho1p action is similar to that of canonical linker histones", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 440, "text": "To identify new proteins involved in spore nuclear organization, we purified chromatin from mature spores and discovered a significant enrichment of the linker histone (Hho1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22586276", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 837, "text": "Hho1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed increased genome-wide binding in mature spores and provides novel in vivo evidence of the linker histone binding to nucleosomal linker DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22586276", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 327, "text": "One of the peculiarities of S. cerevisiae cells is the unusual and less abundant linker histone, Hho1p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Hho1p, the linker histone of Saccharomyces cerevisiae, is important for the proper chromatin organization in vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "endSection": "title" }, { "offsetInBeginSection": 700, "offsetInEndSection": 817, "text": "Characteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Saccharomyces cerevisiae linker histone-Hho1p maintains chromatin loop organization during ageing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24023978", "endSection": "title" }, { "offsetInBeginSection": 359, "offsetInEndSection": 583, "text": "Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11471242", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 361, "text": "Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11471242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Biochemical studies to date have not been able to identify the linker histone H1 protein in the budding yeast Saccharomyces cerevisiae. Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11471242", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 361, "text": "Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11471242", "endSection": "abstract" } ] }, { "body": "What is the role of deadenylases in the cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15247430", "http://www.ncbi.nlm.nih.gov/pubmed/19307292", "http://www.ncbi.nlm.nih.gov/pubmed/23274303", "http://www.ncbi.nlm.nih.gov/pubmed/18056425", "http://www.ncbi.nlm.nih.gov/pubmed/23224971", "http://www.ncbi.nlm.nih.gov/pubmed/18625844", "http://www.ncbi.nlm.nih.gov/pubmed/22614729", "http://www.ncbi.nlm.nih.gov/pubmed/22834816", "http://www.ncbi.nlm.nih.gov/pubmed/12590136", "http://www.ncbi.nlm.nih.gov/pubmed/15475613", "http://www.ncbi.nlm.nih.gov/pubmed/21984185", "http://www.ncbi.nlm.nih.gov/pubmed/23221646", "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "http://www.ncbi.nlm.nih.gov/pubmed/22955276", "http://www.ncbi.nlm.nih.gov/pubmed/17090538", "http://www.ncbi.nlm.nih.gov/pubmed/19111172", "http://www.ncbi.nlm.nih.gov/pubmed/18334997", "http://www.ncbi.nlm.nih.gov/pubmed/21965533", "http://www.ncbi.nlm.nih.gov/pubmed/23496118", "http://www.ncbi.nlm.nih.gov/pubmed/14970390", "http://www.ncbi.nlm.nih.gov/pubmed/23019593" ], "triples": [ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_443256444B36007", "o": "mRNA deadenylase" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503331333834001E", "o": "Cytoplasmic deadenylase" } ], "ideal_answer": [ "The 3'-poly(A) tail, found on mRNAs, is enzymatically shortened by a process referred to as \"deadenylation\" which is carried out by deadenylases. Deadenylases are magnesium dependent exoribonucleases that specifically catalyze the degradation of eukaryotic mRNA poly(A) tail in the 3'-->5' direction with the release of 5'-AMP as the product. They consist of three potential RNA-binding domains: the catalytic nuclease domain, the R3H domain and the RRM domain." ], "concepts": [ "http://www.uniprot.org/uniprot/CNOT6_HUMAN" ], "type": "summary", "id": "5162af0f298dcd4e51000045", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 149, "text": "Deadenylation of eukaryotic mRNA is a mechanism critical for mRNA function by influencing mRNA turnover and efficiency of protein synthesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23496118", "endSection": "sections.0" }, { "offsetInBeginSection": 516, "offsetInEndSection": 696, "text": "In short, PARN is a divalent metal-ion dependent poly(A)-specific, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades poly(A) tails of eukaryotic mRNAs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23496118", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Distinct roles of the R3H and RRM domains in poly(A)-specific ribonuclease structural integrity and catalysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "Deadenylases specifically catalyze the degradation of eukaryotic mRNA poly(A) tail in the 3'- to 5'-end direction with the release of 5'-AMP as the product. Among the deadenylase family, poly(A)-specific ribonuclease (PARN) is unique in its domain composition, which contains three potential RNA-binding domains: the catalytic nuclease domain, the R3H domain and the RRM domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21984185", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 224, "text": "The rate-limiting step of mRNA degradation is the removal of the poly(A) tail by deadenylases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22614729", "endSection": "sections.0" }, { "offsetInBeginSection": 668, "offsetInEndSection": 819, "text": "Purified PUM complexes were found to contain subunits of the CCR4-NOT (CNOT) complex, which contains multiple enzymes that catalyze mRNA deadenylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955276", "endSection": "sections.0" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1381, "text": "These findings demonstrate a conserved mechanism of PUF-mediated repression via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955276", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The activity and selectivity of fission yeast Pop2p are affected by a high affinity for Zn2+ and Mn2+ in the active site.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19307292", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "In eukaryotic organisms, initiation of mRNA turnover is controlled by progressive shortening of the poly-A tail, a process involving the mega-Dalton Ccr4-Not complex and its two associated 3'-5' exonucleases, Ccr4p and Pop2p (Caf1p).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19307292", "endSection": "sections.0" }, { "offsetInBeginSection": 421, "offsetInEndSection": 698, "text": "Here, we show biochemically and structurally that fission yeast (Schizosaccharomyces pombe) Pop2p prefers Mn(2+) and Zn(2+) over Mg(2+) at the concentrations of the ions found inside cells and that the identity of the ions in the active site affects the activity of the enzyme.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19307292", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The 3'-poly(A) tail, found on virtually all mRNAs, is enzymatically shortened by a process referred to as \"deadenylation.\" Deadenylation is a widespread means of controlling mRNA stability and translation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19111172", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Dynamic changes of the lengths of mRNA poly(A) tails are catalysed by diverse deadenylase enzymes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18334997", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "In eukaryotes, shortening of the 3'-poly(A) tail is the rate-limiting step in the degradation of most mRNAs, and two major mRNA deadenylase complexes--Caf1-Ccr4 and Pan2-Pan3--play central roles in this process, referred to as deadenylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056425", "endSection": "sections.0" }, { "offsetInBeginSection": 317, "offsetInEndSection": 471, "text": "Previously, we demonstrated that eukaryotic releasing factor eRF3 mediates deadenylation and decay of mRNA in a manner coupled to translation termination.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056425", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "PUF protein-mediated deadenylation is catalyzed by Ccr4p.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17090538", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Deadenylation of mRNA is often the first and rate-limiting step in mRNA decay. PARN, a poly(A)-specific 3' --> 5' ribonuclease which is conserved in many eukaryotes, has been proposed to be primarily responsible for such a reaction, yet the importance of the PARN function at the whole-organism level has not been demonstrated in any species.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15247430", "endSection": "sections.0" }, { "offsetInBeginSection": 586, "offsetInEndSection": 776, "text": "The trypanosomal deadenylase activity is a 3'-->5' exonuclease specific for adenylate residues, generates 5'-AMP as a product, is magnesium dependent, and is inhibited by neomycin B sulfate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14970390", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Identification of multiple RNA features that influence CCR4 deadenylation activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12590136", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The CCR4 family proteins are 3'-5'-deadenylases that function in the first step of the degradation of poly(A) mRNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12590136", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "PARN, Nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23274303", "endSection": "sections.0" }, { "offsetInBeginSection": 741, "offsetInEndSection": 953, "text": "Thus, deadenylation and the participating deadenylases are not simply required for preparing mRNA substrates; they play an indispensable role both structurally and functionally in P-body formation and regulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23224971", "endSection": "sections.0" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1597, "text": "In this context, the wide repertoire of RBPs and molecules that regulate PARN activity, together with the established role of deadenylases in miRNA-mediated regulation of mRNA expression, suggest that mRNA turnover is more complex than it was previously thought and PARN holds a key role in this process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22834816", "endSection": "sections.0" }, { "offsetInBeginSection": 122, "offsetInEndSection": 330, "text": "A set of multiple poly(A)-specific deadenylases has been identified, some, if not most, of which are likely to play a role in the key first step of mRNA turnover--the regulated shortening of the poly(A) tail.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15475613", "endSection": "sections.0" } ] }, { "body": "What molecule is targeted by brodalumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25093016", "http://www.ncbi.nlm.nih.gov/pubmed/26422722", "http://www.ncbi.nlm.nih.gov/pubmed/24646743", "http://www.ncbi.nlm.nih.gov/pubmed/24200404", "http://www.ncbi.nlm.nih.gov/pubmed/24552447", "http://www.ncbi.nlm.nih.gov/pubmed/24918373", "http://www.ncbi.nlm.nih.gov/pubmed/25599143", "http://www.ncbi.nlm.nih.gov/pubmed/25713988", "http://www.ncbi.nlm.nih.gov/pubmed/25246805", "http://www.ncbi.nlm.nih.gov/pubmed/22455412" ], "ideal_answer": [ "Interleukin-17. Brodalumab is anti interleukin-17 monoclonal antibody." ], "exact_answer": [ "Interleukin-17" ], "type": "factoid", "id": "56bc9268ac7ad1001900001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "BACKGROUND: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26422722", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 559, "text": "METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24552447", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 618, "text": "These include the IL-17 antagonists, secukinumab, brodalumab and ixekizumab; the IL-23 antagonists, guselkumab and tildrakizumab; and the oral small molecule therapies, tofacitinib and apremilast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25713988", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1426, "text": "RECENT FINDINGS: New drugs that are designed to inhibit steps in this pathway, the IL12/IL23 inhibitor, ustekinumab, the IL17A inhibitors secukinumab and ixekizumab, the IL17A receptor inhibitor, brodalumab, and the IL23 inhibitors guselkumab and tildrakizumab, have demonstrated significant effectiveness in treating these diseases, particularly psoriasis, psoriatic arthritis and ankylosing spondylitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25599143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24918373", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22455412", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24200404", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24646743", "endSection": "title" }, { "offsetInBeginSection": 403, "offsetInEndSection": 614, "text": "The three new therapies with biologic drugs - brodalumab, secukinumab, and ixekizumab - all target the IL-17 signaling pathway. Secukinumab and ixekizumab neutralize IL-17A, while brodalumab blocks its receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25246805", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 520, "text": "Brodalumab is a human monoclonal antibody that targets IL-17 receptor A,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093016", "endSection": "abstract" } ] }, { "body": "How long, in kb (kilobases), is a \"Long interspersed nuclear element\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11810275", "http://www.ncbi.nlm.nih.gov/pubmed/21916613", "http://www.ncbi.nlm.nih.gov/pubmed/21637438" ], "ideal_answer": [ "The retrotransposon known as long interspersed nuclear element-1 (L1) is 6-7 kb long," ], "exact_answer": [ "6-7 kb" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020084", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004602", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020071" ], "type": "factoid", "id": "54ff5197e9bde69634000001", "snippets": [ { "offsetInBeginSection": 457, "offsetInEndSection": 633, "text": " A combination of molecular hybridization studies and long-range polymerase chain reaction was used to isolate a 6-kb full-length long interspersed nuclear element (LINE or L1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11810275", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 512, "text": "LINE (7kb long interspersed nuclear element),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21916613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The retrotransposon known as long interspersed nuclear element-1 (L1) is 6 kb long, although most L1s in mammalian and other eukaryotic cells are truncated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21637438", "endSection": "abstract" } ] }, { "body": "Which is the gene mutated in type 1 neurofibromatosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20442305", "http://www.ncbi.nlm.nih.gov/pubmed/9326316", "http://www.ncbi.nlm.nih.gov/pubmed/7485153", "http://www.ncbi.nlm.nih.gov/pubmed/8528106", "http://www.ncbi.nlm.nih.gov/pubmed/8699317", "http://www.ncbi.nlm.nih.gov/pubmed/9190537", "http://www.ncbi.nlm.nih.gov/pubmed/17573495", "http://www.ncbi.nlm.nih.gov/pubmed/17209131", "http://www.ncbi.nlm.nih.gov/pubmed/16741618", "http://www.ncbi.nlm.nih.gov/pubmed/10973261", "http://www.ncbi.nlm.nih.gov/pubmed/16861979", "http://www.ncbi.nlm.nih.gov/pubmed/8845843", "http://www.ncbi.nlm.nih.gov/pubmed/11257108", "http://www.ncbi.nlm.nih.gov/pubmed/10874316", "http://www.ncbi.nlm.nih.gov/pubmed/23578956", "http://www.ncbi.nlm.nih.gov/pubmed/10712197", "http://www.ncbi.nlm.nih.gov/pubmed/9668168", "http://www.ncbi.nlm.nih.gov/pubmed/12695655", "http://www.ncbi.nlm.nih.gov/pubmed/18196300", "http://www.ncbi.nlm.nih.gov/pubmed/8264648", "http://www.ncbi.nlm.nih.gov/pubmed/15770836", "http://www.ncbi.nlm.nih.gov/pubmed/17019046", "http://www.ncbi.nlm.nih.gov/pubmed/17564507", "http://www.ncbi.nlm.nih.gov/pubmed/17295913", "http://www.ncbi.nlm.nih.gov/pubmed/21354044" ], "ideal_answer": [ "NF1 gene, encoding neurofibromin 1" ], "exact_answer": [ "NF1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025542", "http://www.uniprot.org/uniprot/NF1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016514", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009456", "http://www.uniprot.org/uniprot/NF1_HUMAN", "http://www.uniprot.org/uniprot/NF1_CHICK", "http://www.disease-ontology.org/api/metadata/DOID:8712", "http://www.uniprot.org/uniprot/NF1_MOUSE" ], "type": "factoid", "id": "5343fc1aaeec6fbd07000003", "snippets": [ { "offsetInBeginSection": 190, "offsetInEndSection": 238, "text": "Individuals with NF1 harbor 1 mutated NF1 allele", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23578956", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 91, "text": "type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21354044", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 298, "text": "The NF1 gene, mutated in NF1, is also commonly mutated in sporadic glioblastoma multiforme (GBM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442305", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 120, "text": " type 1 (NF1) is a common genetic disease caused by haploinsufficiency of the NF1 tumor-suppressor gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18196300", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 149, "text": "Neurofibromatosis type 1 (NF1) is a common disorder of dysregulated tissue growth secondary to mutations in the tumor suppressor gene NF1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17573495", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 969, "text": "tumor suppressor protein neurofibromin, which is mutated in NF1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17564507", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 187, "text": " Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, affecting about 1:3,500 individuals. NF1 exon 7 displays weakly defined exon-intron boundaries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17295913", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 635, "text": "Loss of heterozygosity (LOH) of NF1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209131", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 121, "text": "Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder resulting in the growth of a variety of tumours, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209131", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 404, "text": "ten occur in both children and adults as sporadic events with no family history of the disease, but they are also among the clinical manifestations of a significant number of familial cancer syndromes, including familial retinoblastoma, neurofibromatosis 1 and 2, tuberous sclerosis, and Cowden, Turcot, Li-Fraumeni and nevoid basal cell carcinoma (Gorlin) syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17019046", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 663, "text": "These genes include RB1, NF1, NF2, TSC1, TSC2, TP53, PTEN, APC, hMLH1, hPSM2, and PTCH", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17019046", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 194, "text": "von Recklinghausen syndrome (NF-1) (OMIM 162200) carrying NF1 germline mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16861979", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 97, "text": "mutations of the NF1 gene have been reported in patients with neurofibromatosis type 1 (NF1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16741618", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 76, "text": "NF1 gene mutation in a Japanese patient with neurofibromatosis type 1 ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16741618", "endSection": "title" }, { "offsetInBeginSection": 328, "offsetInEndSection": 470, "text": "Neurofibromatosis 1 gene (NF1 ) fulfills the criteria of a tumor suppressor gene and is deleted or mutated heterozygously in patients with NF1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15770836", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 208, "text": "type 1 (NF1) is one of the most common human genetic disorders and is associated with significant morbidity and mortality. The gene responsible for this disorder, NF1, encodes neurofibromin,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12695655", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 415, "text": " genes mutated in these two disorders encode tumor suppressor proteins, termed neurofibromin (NF1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11257108", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 664, "text": " tumour-suppressor genes, Nf1 and Trp53. Humans with mutations in NF1 develop neurofibromatosis type I (NF1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10973261", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 187, "text": "type 1 (NF1) is an autosomal dominant genetic disorder affecting one in 3,500 individuals. The mutation rate in the NF1 gene is one of the highest known for human genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10874316", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 113, "text": "patients with neurofibromatosis type 1 (NF1) were screened for mutations in the NF1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10712197", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 338, "text": "It is caused by a wide spectrum of mutations affecting the NF1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9668168", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 121, "text": "NF1) is a common familial tumour syndrome with multiple clinical features such as neurofibromas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9668168", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 257, "text": "This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called \"neurofibromin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9326316", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 237, "text": "type 1 (NF1) and type 2 (NF2) are connected with genes localized on chromosomes 17 and 22, respectively. The genes that are inactivated in neurofibromatosis code for the proteins neurofibromine and merline", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9190537", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 530, "text": "neurofibromatosis type 1 (NF1) gene, well recognized for its high frequency of spontaneous mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8845843", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 648, "text": "An NF1 gene was identified as a gene whose loss of function causes an onset of human disorder, neurofibromatosis type I.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8699317", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 118, "text": "type 1 (NF1) is caused by deletions, insertions, translocations, and point mutations in the NF1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7485153", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 103, "text": "type 1 (NF1) gene is a tumor suppressor gene, and the NF1 gene product, neurofibromin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8528106", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 119, "text": "ysine 1423 of neurofibromin (neurofibromatosis type I gene product [NF1]) plays a crucial role in the function of NF1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8264648", "endSection": "abstract" } ] }, { "body": "List receptors of the drug Cilengitide", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22517378", "http://www.ncbi.nlm.nih.gov/pubmed/25486381", "http://www.ncbi.nlm.nih.gov/pubmed/23728220", "http://www.ncbi.nlm.nih.gov/pubmed/12706360", "http://www.ncbi.nlm.nih.gov/pubmed/17896915", "http://www.ncbi.nlm.nih.gov/pubmed/23948974", "http://www.ncbi.nlm.nih.gov/pubmed/21739168", "http://www.ncbi.nlm.nih.gov/pubmed/21049281", "http://www.ncbi.nlm.nih.gov/pubmed/18981465", "http://www.ncbi.nlm.nih.gov/pubmed/21914576", "http://www.ncbi.nlm.nih.gov/pubmed/24328341", "http://www.ncbi.nlm.nih.gov/pubmed/23060541", "http://www.ncbi.nlm.nih.gov/pubmed/16729916", "http://www.ncbi.nlm.nih.gov/pubmed/19929817", "http://www.ncbi.nlm.nih.gov/pubmed/24433287", "http://www.ncbi.nlm.nih.gov/pubmed/22582818", "http://www.ncbi.nlm.nih.gov/pubmed/20648558", "http://www.ncbi.nlm.nih.gov/pubmed/17693653", "http://www.ncbi.nlm.nih.gov/pubmed/21269250", "http://www.ncbi.nlm.nih.gov/pubmed/12154028", "http://www.ncbi.nlm.nih.gov/pubmed/24595274", "http://www.ncbi.nlm.nih.gov/pubmed/21827415", "http://www.ncbi.nlm.nih.gov/pubmed/20029421", "http://www.ncbi.nlm.nih.gov/pubmed/21512659", "http://www.ncbi.nlm.nih.gov/pubmed/23152080", "http://www.ncbi.nlm.nih.gov/pubmed/23229276", "http://www.ncbi.nlm.nih.gov/pubmed/18838556", "http://www.ncbi.nlm.nih.gov/pubmed/20820929", "http://www.ncbi.nlm.nih.gov/pubmed/18779539" ], "ideal_answer": [ "Cilengitide binds \u03b1v\u03b23 and \u03b1v\u03b25 integrins. It inhibits attachment and invasion of malignant cells. Thus, cilengitide is being tested for treatment of cancer patients." ], "exact_answer": [ [ "\u03b1v\u03b23 integrin" ], [ "\u03b1\u03bd\u03b25 integrin" ], [ "\u03b1v\u03b25", "\u03b1v\u03b23" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4242009" ], "type": "list", "id": "54cf705ff693c3b16b000014", "snippets": [ { "offsetInBeginSection": -1, "offsetInEndSection": 130, "text": "Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins \u03b1v\u03b23 and \u03b1v\u03b25.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595274", "endSection": "title" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1764, "text": "Also, this dimer bound 3650-fold stronger and inhibited tumor cell migration and proliferation compared with cilengitide, an integrin-targeting peptidomimetic that performed poorly in recent clinical trials, suggesting promise for further therapeutic development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25486381", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 727, "text": "As there is evidence for expression of the integrins \u03b1v\u03b23 and \u03b1v\u03b25 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin \u03b1v heterodimer with high specificity for \u03b1v\u03b23 and \u03b1v\u03b25. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595274", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1186, "text": "Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of \u03b1v\u03b23 and \u03b1v\u03b25.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Abstract The RGD cyclic pentapetide, cilengitide, is a selective inhibitor of \u03b1v\u03b23 and \u03b1v\u03b25 integrins and was developed for antiangiogenic therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24433287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was was developed as a highly active and selective ligand for the \u03b1v\u03b23 and \u03b1v\u03b25 integrin receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24328341", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 793, "text": "RESULTS: \u03b1v\u03b25 was the predominantly expressed integrin heterodimer in meningiomas, whereas \u03b1v\u03b23 was mainly detected in tumor blood vessels. Application of up to 100 \u03bcg/mL cilengitide resulted in only mildly reduced proliferation/survival of meningioma cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23948974", "endSection": "abstract" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1066, "text": "UW479 cells expressed only \u03b1v\u03b25 integrin and were not sensitive to cilengitide, suggesting that cilengitide's action largely depends on \u03b1v\u03b23 inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728220", "endSection": "abstract" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1629, "text": "Cilengitide's action on glioma and neuroblastoma cells appears to be dependent on \u03b1v\u03b23 expression and sensitivity to anoikis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728220", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 542, "text": "METHODS: For this purpose, nude rats bearing bone metastases were treated with cilengitide, a small molecule inhibitor of \u03b1v\u03b23 and \u03b1v\u03b25 integrins, from day 30 to 55 after tumor cell inoculation of MDA-MB-231 breast cancer cells (25 mg/kg, 5 days per week; n = 8 rats) and compared to control rats (n = 8). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229276", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 124, "text": "The \u03b1V\u03b23/\u03b1V\u03b25 integrin inhibitor cilengitide augments tumor response to melphalan isolated limb perfusion in a sarcoma model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152080", "endSection": "title" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1385, "text": "Cilengitide, a cyclized Arg-Gly-Glu(RGD)-containing pentapeptide that selectively blocks activation of the \u03b1v\u03b23 and \u03b1v\u03b25 integrins has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23060541", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 871, "text": " Aza-amino acid scanning was performed on the cyclic RGD-peptide Cilengitide, cyclo[R-G-D-f-N(Me)V] 1, and its parent peptide cyclo(R-G-D-f-V) 2, potent antagonists of the \u03b1v\u03b23, \u03b1v\u03b25, and \u03b15\u03b21 integrin receptors, which play important roles in human tumor metastasis and tumor-induced angiogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22582818", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 244, "text": "Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) is a new drug targeting \u03b1v\u03b23 and \u03b1v\u03b25 integrins thanks to a specific peptide called RGD sequence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21914576", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 669, "text": "Cilengitide, a cyclic RGD-mimetic peptide of \u03b1v\u03b23 and \u03b1v\u03b25 integrins is in advanced clinical development in glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21827415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the \u03b1\u03bd\u03b2 3 and \u03b1\u03bd\u03b2 5 integrin receptors in rats with breast cancer bone metastases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512659", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 269, "text": "We conducted a phase II study of cilengitide, a selective antagonist of \u03b1(v)\u03b2(3) and \u03b1(v)\u03b2(5) integrins, in non-metastatic castration resistant prostate cancer with rising PSA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21049281", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 346, "text": "AlphaVbeta3 and alphaVbeta5 integrins are overexpressed on both glioma cells and tumor vasculature. Cilengitide, the most advanced specific integrin inhibitor in oncology, has shown antitumor activity against glioma in early clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20820929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 468, "text": "The aim of this study was to investigate the effect of inhibiting \u03b1v\u03b2(3)/\u03b1(v) \u03b2(5) integrins by cilengitide in experimentally induced breast cancer bone metastases using noninvasive imaging techniques. For this purpose, nude rats bearing established breast cancer bone metastases were treated with cilengitide, a small molecule inhibitor of \u03b1v\u03b2(3) and \u03b1v\u03b2(5) integrins (75 mg/kg, five days per week; n = 12 rats) and compared to vehicle-treated control rats (n = 12). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648558", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1488, "text": " In conclusion, treatment of experimental breast cancer bone metastases with cilengitide resulted in pronounced antiresorptive and antitumor effects, suggesting that \u03b1v\u03b2(3)/\u03b1v\u03b2(5) inhibition may be a promising therapeutic approach for bone metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648558", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 543, "text": "Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20029421", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1108, "text": "Cilengitide (cyclic peptidic alphavbeta3 and alphavbeta5 antagonist) is currently in clinical trials for anti cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19929817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "PURPOSE: Cilengitide, an inhibitor of alphavbeta3 and alphavbeta5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18981465", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 865, "text": "In line with this concept, peptide ligands containing the Arginine-Glycine-Aspartate (RGD) triad, which display a strong affinity and selectivity to the alpha(V)beta(3) integrin, have been developed to target the tumor-associated cells expressing the alpha (V)beta (3) receptors. Among the validated ligands, the leader compound is the cyclic pentapeptide c[-RGDf(NMe)V-] (Cilengitide) developed by kessler et al. (J. Med. Chem., 1999, 42, 3033-3040). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17896915", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 192, "text": "Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17693653", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "BACKGROUND: Cilengitide, an antiangiogenic agent that inhibits the binding of integrins alpha(nu)beta(3) and alpha(nu)beta(5) to the extracellular matrix, was studied at two dose levels in cancer patients to determine the optimal biological dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17693653", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 397, "text": "Cilengitide (EMD121974; NSC 707544), is a potent selective alphavbeta3 and alphavbeta5 integrin antagonist. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16729916", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 219, "text": "Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12706360", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "A single-agent dose escalating phase I and pharmacokinetic study with Cilengitide, an inhibitor of the integrins alphavbeta3 and alphavbeta5, was performed to determine its safety and toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12706360", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 767, "text": "This study was designed to determine whether, and how, the cyclic Arg-Gly-Asp peptide Cilengitide (EMD 121974), which targets the alpha(v)beta(3) integrin receptor expressed on neovasculature, could increase systemic RIT efficacy of therapy in a human breast cancer tumor model having mutant p53 and expressing bcl-2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12154028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the \u03b1\u03bd\u03b2 3 and \u03b1\u03bd\u03b2 5 integrin receptors in rats with breast cancer bone metastases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512659", "endSection": "abstract" } ] }, { "body": "Can protein coding exons originate from ALU sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15328599", "http://www.ncbi.nlm.nih.gov/pubmed/21282640", "http://www.ncbi.nlm.nih.gov/pubmed/21188497", "http://www.ncbi.nlm.nih.gov/pubmed/20803091", "http://www.ncbi.nlm.nih.gov/pubmed/18332115", "http://www.ncbi.nlm.nih.gov/pubmed/20532223", "http://www.ncbi.nlm.nih.gov/pubmed/17594509", "http://www.ncbi.nlm.nih.gov/pubmed/19393186", "http://www.ncbi.nlm.nih.gov/pubmed/17204284", "http://www.ncbi.nlm.nih.gov/pubmed/23374342", "http://www.ncbi.nlm.nih.gov/pubmed/15099521", "http://www.ncbi.nlm.nih.gov/pubmed/18047649", "http://www.ncbi.nlm.nih.gov/pubmed/19324900", "http://www.ncbi.nlm.nih.gov/pubmed/15901843", "http://www.ncbi.nlm.nih.gov/pubmed/16027113", "http://www.ncbi.nlm.nih.gov/pubmed/23303787", "http://www.ncbi.nlm.nih.gov/pubmed/12764196" ], "ideal_answer": [ "Yes. Intronic ALUs can evolve into exons by the activation of splice signals residing within the ALU sequence. While most ALU exons do not add or modify the coding capacity of the resulting transcript, examples have been identified of ALU exons becoming protein coding." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020087", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005091" ], "type": "yesno", "id": "51763a278ed59a060a000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The Alu element has been a major source of new exons during primate evolution. Thousands of human genes contain spliced exons derived from Alu elements.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282640", "endSection": "sections.0" }, { "offsetInBeginSection": 476, "offsetInEndSection": 671, "text": "More than 25% of Alu exons analyzed by RNA-Seq have estimated transcript inclusion levels of at least 50% in the human cerebellum, indicating widespread establishment of Alu exons in human genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282640", "endSection": "sections.0" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1388, "text": "his study presents genomic evidence that a major functional consequence of Alu exonization is the lineage-specific evolution of translational regulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282640", "endSection": "sections.0" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1500, "text": "Our data suggests that lineage-specific exonization events should be determined by the combination event of the formation of splicing sites and protection against site-specific mutation pressures. These evolutionary mechanisms could be major sources for primate diversification.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20803091", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Exonization of Alu elements creates primate-specific genomic diversity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18332115", "endSection": "sections.0" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1158, "text": "Our data show that, once acquired, some exonizations were lost again in some lineages. In general, Alu exonization occurred at various time points over the evolutionary history of primate lineages, and protein-coding potential was acquired either relatively soon after integration or millions of years thereafter.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15901843", "endSection": "sections.0" }, { "offsetInBeginSection": 131, "offsetInEndSection": 355, "text": "Once integrated, they have the potential to become exapted as functional modules, e.g., as protein-coding domains via alternative splicing. This particular process is also termed exonization and increases protein versatility", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15901843", "endSection": "sections.0" }, { "offsetInBeginSection": 125, "offsetInEndSection": 288, "text": "alternative \"Alu-exons\" also carry the potential to greatly enhance genetic diversity by increasing the transcriptome of primates chiefly via alternative splicing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15328599", "endSection": "sections.0" }, { "offsetInBeginSection": 289, "offsetInEndSection": 528, "text": "ere, we report a 5' exon generated from one of the two alternative transcripts in human tumor necrosis factor receptor gene type 2 (p75TNFR) that contains an ancient Alu-SINE, which provides an alternative N-terminal protein-coding domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15328599", "endSection": "sections.0" } ] }, { "body": "How could U1 small nuclear RNA be used in therapeutics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22362925", "http://www.ncbi.nlm.nih.gov/pubmed/22968481", "http://www.ncbi.nlm.nih.gov/pubmed/20869034", "http://www.ncbi.nlm.nih.gov/pubmed/19219028", "http://www.ncbi.nlm.nih.gov/pubmed/22454066", "http://www.ncbi.nlm.nih.gov/pubmed/22454067", "http://www.ncbi.nlm.nih.gov/pubmed/21520335", "http://www.ncbi.nlm.nih.gov/pubmed/21326217" ], "ideal_answer": [ "Until now, two main types of therapeutic strategies have been developed using U1 small nuclear RNA (snRNA): 1) Production of a defective, but partially functional protein, with the help of exon skipping, through modulation of pre-mRNA splicing, and 2) Correction of pathogenic effects of splice donor site mutations with the use of U1 snRNA adapted to the defective variant." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000394", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0017069", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012322", "http://www.uniprot.org/uniprot/PRP24_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000398", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000395", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012342", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070054", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000379", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000373", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000372", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008380", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022821", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043484", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000375", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000374", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016180", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030623", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030620", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030621", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030626", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030625", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0017070", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071209", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040031", "http://www.uniprot.org/uniprot/SF01_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030619", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000365", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051030", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048024", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000945", "http://www.uniprot.org/uniprot/SUGP1_HUMAN" ], "type": "summary", "id": "5357a514f1005d6b58000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Exon 45 skipping through U1-snRNA antisense molecules recovers the Dys-nNOS pathway and muscle differentiation in human DMD myoblasts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968481", "endSection": "title" }, { "offsetInBeginSection": 200, "offsetInEndSection": 382, "text": "Here, we show the selection of U1 snRNA-antisense constructs able to confer effective rescue of dystrophin synthesis in a \u039444 Duchenne genetic background, through skipping of exon 45", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968481", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 521, "text": "U1 small nuclear RNA have been used to carry antisense sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454067", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 955, "text": "we showed that bifunctional U7 snRNAs harboring silencer motifs induce complete skipping of exon 51, and thus restore dystrophin expression in DMD patients cells to near wild-type levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454067", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1161, "text": "These new constructs are very promising for the optimization of therapeutic exon skipping for DMD, but also offer powerful and versatile tools to modulate pre-mRNA splicing in a wide range of applications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "U1 snRNA as an effective vector for stable expression of antisense molecules and for the inhibition of the splicing reaction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454066", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "We report the use of the U1 snRNA as a vector for the stable expression of antisense molecules against the splice junctions of specific dystrophin exons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454066", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 470, "text": "Effective exon skipping has been obtained for different dystrophin exons by antisense sequences against 5' and 3' splice sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454066", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1254, "text": "the U1-antisense molecules, delivered to mice via systemic injection of recombinant AAV viruses, displayed body wide transduction, long-term expression, dystrophin rescue as well as morphological and functional benefit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "U1 snRNA-mediated gene therapeutic correction of splice defects caused by an exceptionally mild BBS mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21520335", "endSection": "title" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1132, "text": "For a gene therapeutic approach, we have adapted the sequence of U1 to increase its complementarity to the mutated SD. Lentiviral treatment of patient-derived fibroblasts with the adapted U1 partially corrected aberrant splicing of endogenously expressed BBS1 transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21520335", "endSection": "abstract" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1328, "text": "Our results show that the adaptation of U1 can correct pathogenic effects of splice donor site mutations and suggest a high potential for gene therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21520335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Gene therapeutic approach using mutation-adapted U1 snRNA to correct a RPGR splice defect in patient-derived cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21326217", "endSection": "title" }, { "offsetInBeginSection": 504, "offsetInEndSection": 623, "text": "To correct the splice defect, we developed a gene therapeutic approach using mutation-adapted U1 small nuclear RNA (U1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21326217", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1251, "text": "Full complementarity of U1 corrects the splice defect partially and increases recognition of the mutant SDS. The therapeutic effect is U1-concentration dependent as we show for endogenously expressed RPGR transcripts in patient-derived cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21326217", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1391, "text": "U1-based gene therapeutic approaches constitute promising technologies to treat SDS mutations in inherited diseases including X-linked RP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21326217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20869034", "endSection": "title" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1487, "text": "use of lentiviral vectors as a delivery system to introduce expression cassettes for TT-adapted U1 snRNAs into primary FANCC patient fibroblasts allowed the correction of the DNA-damage-induced G2 cell-cycle arrest in these cells, thus representing an alternative transcript-targeting approach for genetic therapy of inherited splice-site mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20869034", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 418, "text": "Using F9 exon 5, CFTR exon 12 and SMN2 exon 7 models, we characterized natural mutations associated to exon skipping in Haemophilia B, cystic fibrosis and spinal muscular atrophy (SMA), respectively, and the therapeutic splicing rescue by using U1 small nuclear RNA (snRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362925", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 389, "text": "U1 Adaptors are bifunctional oligonucleotides with a 'target domain' complementary to a site in the target gene's terminal exon and a 'U1 domain' that binds to the U1 small nuclear RNA component of the U1 small nuclear ribonucleoprotein (U1 snRNP) splicing factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19219028", "endSection": "abstract" } ] }, { "body": "What is the influence of patent expiry on ACE inhibitor prescribing.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21738055", "http://www.ncbi.nlm.nih.gov/pubmed/16309337", "http://www.ncbi.nlm.nih.gov/pubmed/22521158" ], "ideal_answer": [ "Patent expiry has different effects on prescribing in different systems. It leads to decreased cost but no decreased refill compliance in countries like Sweden, Germany etc. In countries like Taiwan, where doctors profit directly from dispensing, patients are switched to ARBs which are more costly." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000806" ], "type": "summary", "id": "5150b5c4d24251bc05000070", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Generic switch after ramipril patent expiry is not associated with decreased pharmacy refill compliance: a retrospective study using the DAPI database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21738055", "endSection": "title" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1333, "text": "The costs per DDD decreased for all three drugs and, as expected, these costs decrease more rapidly after patent expiry. Significant differences in the trend lines were found for enalapril and fluoxetine", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16309337", "endSection": "sections.0" } ] }, { "body": "Is there evidence that tomato juice lowers cholesterol levels?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22098224", "http://www.ncbi.nlm.nih.gov/pubmed/22223578", "http://www.ncbi.nlm.nih.gov/pubmed/17617941", "http://www.ncbi.nlm.nih.gov/pubmed/21755327", "http://www.ncbi.nlm.nih.gov/pubmed/24392102" ], "ideal_answer": [ "Yes, there is evidence to suggest that tomato juice (and other tomato products) can decrease cholesterol concentrations. It was shown that tomatoes inhibit cholesterol biosynthesis." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4271425", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002784", "http://www.biosemantics.org/jochem#4271425" ], "type": "yesno", "id": "56c1d85cef6e394741000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The hypocholesterolemic effect of tomato juice has been investigated in an intervention study with rats, along with the possible inhibition effect of bioactive tomato compounds binding to the HMGCR enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392102", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1250, "text": "The molecular modelling showed that components of tomato can bind to the active site of the enzyme and compete with the ligand HMGCoA. Lycopene, from tomato juice, accumulates in the liver and can inhibit the activity of the rate-limiting enzyme of cholesterol biosynthesis, HMGCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392102", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1215, "text": " Juice consumption significantly improved resistance of LDL+VLDL-C to Cu(2+)-mediated oxidation (P = 0.039), HDL-C (47.3 \u00b1 15.8 to 51.7 \u00b1 14.8 mg/dL, P<0.001), and the ratio of total-C/HDL-C (4.25 \u00b1 1.59 to 3.63 \u00b1 1.16, P<0.001) at 8 wk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22098224", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 832, "text": "RESULTS: Intervention with the enriched juice had no effect on the lipid profile, and serum levels of triglycerides and cholesterol (total, LDL, and HDL) remained unchanged. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21755327", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1510, "text": "Women consuming \u226510 compared with<1.5 servings/wk of tomato-based food products had significant but clinically modest improvements in total cholesterol (TC) (5.38 vs. 5.51 mmol/L; P = 0.029), the TC:HDL cholesterol ratio (4.08 vs. 4.22; P = 0.046), and hemoglobin A1c (5.02 vs. 5.13%; P<0.001) in multivariable models. Considering clinical cutpoints, women consuming \u226510 compared with<1.5 servings/wk were 31% (95% CI = 6%, 50%), 40% (95% CI = 13%, 59%), and 66% (95% CI = 20%, 86%) less likely to have elevated TC (\u22656.21 mmol/L), LDL cholesterol (\u22654.14 mmol/L), and hemoglobin A1c (\u22656%), respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223578", "endSection": "abstract" }, { "offsetInBeginSection": 1587, "offsetInEndSection": 1823, "text": "In conclusion, women consuming \u226510 compared with<1.5 servings/wk of tomato-based food products had clinically modest but significant improvements in TC, the TC:HDL cholesterol ratio, and hemoglobin A1c but not other coronary biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17617941", "endSection": "title" }, { "offsetInBeginSection": 536, "offsetInEndSection": 734, "text": "Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17617941", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1400, "text": "In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17617941", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 833, "text": "Total, LDL and HDL cholesterol were significantly lower in the intervention group after the intake of tomato juice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392102", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 735, "text": "Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17617941", "endSection": "abstract" } ] }, { "body": "Are there transposon-free regions in mammalian genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18093339", "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "http://www.ncbi.nlm.nih.gov/pubmed/21515576" ], "ideal_answer": [ "Yes. Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation." ], "exact_answer": "yes", "type": "yesno", "id": "56c44ce83aaba2a675000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Transposon-free regions in mammalian genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 963, "text": "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1131, "text": "All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21515576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 562, "text": "RESULTS: Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18093339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 958, "text": "All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21515576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 542, "text": "Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18093339", "endSection": "abstract" } ] }, { "body": "Are messenger RNA molecules epigenetically methylated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26121403", "http://www.ncbi.nlm.nih.gov/pubmed/24768686", "http://www.ncbi.nlm.nih.gov/pubmed/25469751", "http://www.ncbi.nlm.nih.gov/pubmed/24480744", "http://www.ncbi.nlm.nih.gov/pubmed/25378335", "http://www.ncbi.nlm.nih.gov/pubmed/26458103", "http://www.ncbi.nlm.nih.gov/pubmed/25430002" ], "ideal_answer": [ "Yes, methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012333", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0080188", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032259", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036265", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001510" ], "type": "yesno", "id": "56d2ee61f22319765a000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The most abundant mRNA post-transcriptional modification is N(6)-methyladenosine (m(6)A), which has broad roles in RNA biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26458103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26121403", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 742, "text": " Recently, methylation patterns have also been revealed in mRNA. Surprisingly, the two most commonly studied methylation states in mRNA (m6A and m5C) are found to be enriched in 3'-UTRs (untranslated regions), the target site for the majority of miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25469751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "MeT-DB: a database of transcriptome methylation in mammalian cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378335", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. The MethylTranscriptome DataBase (MeT-DB, http://compgenomics.utsa.edu/methylation/) is the first comprehensive resource for N6-methyladenosine (m(6)A) in mammalian transcriptome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Mammalian messenger RNA (mRNA) and long noncoding RNA (lncRNA) contain tens of thousands of posttranscriptional chemical modifications. Among these, the N(6)-methyl-adenosine (m(6)A) modification is the most abundant and can be removed by specific mammalian enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24768686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Recent discoveries of reversible N(6)-methyladenosine (m(6)A) methylation on messenger RNA (mRNA) and mapping of m(6)A methylomes in mammals and yeast have revealed potential regulatory functions of this RNA modification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430002", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 543, "text": "There are several identified methylation modifications in eukaryotic messenger RNA (mRNA), such as N(7)-methylguanosine (m(7)G) at the cap, N(6)-methyl-2'-O-methyladenosine (m(6)Am), 2'-O-methylation (Nm) within the cap and the internal positions, and internal N(6)-methyladenosine (m(6)A) and 5-methylcytosine (m(5)C).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24480744", "endSection": "abstract" } ] }, { "body": "Which genes are more frequently affected by somatic mutations in Chronic Lymphocytic Leukemia", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19367498", "http://www.ncbi.nlm.nih.gov/pubmed/10803511", "http://www.ncbi.nlm.nih.gov/pubmed/21642962", "http://www.ncbi.nlm.nih.gov/pubmed/22158541", "http://www.ncbi.nlm.nih.gov/pubmed/22150006", "http://www.ncbi.nlm.nih.gov/pubmed/22675518" ], "ideal_answer": [ "TP53, ATM, NOTCH1, XPO1, MYD88, KLHL6, SF3B1, ZMYM3, MAPK1, FBXW7 and DDX3X" ], "exact_answer": [ [ "TP53" ], [ "ATM" ], [ "NOTCH1" ], [ "XPO1" ], [ "MYD88" ], [ "KLHL6" ], [ "SF3B1" ], [ "ZMYM3" ], [ "MAPK1" ], [ "FBXW7" ], [ "DDX3X" ] ], "type": "list", "id": "5171a1498ed59a060a000012", "snippets": [ { "offsetInBeginSection": 333, "offsetInEndSection": 497, "text": "Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22158541", "endSection": "sections.0" }, { "offsetInBeginSection": 583, "offsetInEndSection": 815, "text": "Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642962", "endSection": "sections.0" }, { "offsetInBeginSection": 476, "offsetInEndSection": 917, "text": "Nine genes that are mutated at significant frequencies were identified, including four with established roles in chronic lymphocytic leukemia (TP53 in 15% of patients, ATM in 9%, MYD88 in 10%, and NOTCH1 in 4%) and five with unestablished roles (SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X). SF3B1, which functions at the catalytic core of the spliceosome, was the second most frequently mutated gene (with mutations occurring in 15% of patients).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22150006", "endSection": "sections.0" } ] }, { "body": "How effective is the dentritic cells treatment on cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11022098", "http://www.ncbi.nlm.nih.gov/pubmed/22042118", "http://www.ncbi.nlm.nih.gov/pubmed/22230748", "http://www.ncbi.nlm.nih.gov/pubmed/23369287", "http://www.ncbi.nlm.nih.gov/pubmed/23684423", "http://www.ncbi.nlm.nih.gov/pubmed/11570584", "http://www.ncbi.nlm.nih.gov/pubmed/17986000", "http://www.ncbi.nlm.nih.gov/pubmed/18684638", "http://www.ncbi.nlm.nih.gov/pubmed/20811715", "http://www.ncbi.nlm.nih.gov/pubmed/21895989", "http://www.ncbi.nlm.nih.gov/pubmed/16221071", "http://www.ncbi.nlm.nih.gov/pubmed/19968878" ], "ideal_answer": [ "Another approach to cancer therapy takes advantage of the normal role of the dendritic cell as an immune educator. Dendritic cells grab antigens from viruses, bacteria, or other organisms and wave them at T cells to recruit their help in an initial T cell immune response. This works well against foreign cells that enter the body, but cancer cells often evade the self/non-self detection system. By modifying dendritic cells, researchers are able to trigger a special kind of autoimmune response that includes a T cell attack of the cancer cells. Because a cancer antigen alone is not enough to rally the immune troops, scientists first fuse a cytokine to a tumor antigen with the hope that this will send a strong antigenic signal. Next, they grow a patient's dendritic cells in the incubator and let them take up this fused cytokine-tumor antigen. This enables the dendritic cells to mature and eventually display the same tumor antigens as appear on the patient's cancer cells. When these special mature dendritic cells are given back to the patient, they wave their newly acquired tumor antigens at the patient's immune system, and those T cells that can respond mount an attack on the patient's cancer cells." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016609", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024221", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "summary", "id": "5321bc029b2d7acc7e00000c", "snippets": [ { "offsetInBeginSection": 4, "offsetInEndSection": 530, "text": "BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23684423", "endSection": "abstract" }, { "offsetInBeginSection": 22, "offsetInEndSection": 920, "text": " silencing of suppressor of cytokine signalling 1 (Socs1) or stably expressing transgenic protein Ags in antigen-presenting dentritic cells (DCs) strongly enhances antigen-specific anti-tumour immunity. However, whether the strong and long-lasting T cell responses induced by the modified DCs could modulate the immunosuppressive tumour microenvironment has not been clarified. In this study, we explored the anti-tumour immunity of DCs modified by Socs1-shRNA lentiviral transduction combined with sustained expression of TRP2 in different tumour models. We showed that transfer Socs1-silenced or tumour antigen TRP2 persistent expressed DCs, or DCs modified by combination of Socs1-silencing and sustaining TRP2 expression prior to inoculation of tumour cells delayed B16 tumour cell growth, prolonged mouse survival and increased the ratio of CD8+ T/Treg as well as the CTL activity in tumours. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22230748", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 294, "text": "To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22042118", "endSection": "abstract" }, { "offsetInBeginSection": 1481, "offsetInEndSection": 2028, "text": "Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1. Our study describes for the first time the density of subepithelial DC-SIGN+ dendritic cells in patients with anal severe anal intraepithelial neoplasia and points to the possibility that a specific therapy for HIV ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22042118", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 1078, "text": "transfer of CD40 ligand (CD40L) holds promise as a novel therapy for lymphoid malignancies and a number of solid carcinomas because of its multiple anti-tumor activities. However, membrane-bound CD40L can be cleaved into a soluble form, sCD40L, which contributes to systemic inflammatory and cardiovascular diseases, and induces survival signals in the absence of protein synthesis block, suggesting a deleterious side effect of CD40L gene therapy. We generated a plasmid encoding non-cleavable human CD40L mutant (pcDNA3.1+-CD40L-M) to determine the direct anti-proliferative and pro-apoptotic effects in CD40-positive lung adenocarcinoma cell line A549, to verify activation of immature dentritic cells (DCs) by co-cultivation with the transfected A549 cells and to evaluate the lower expression of sCD40L relative to that of wild-type CD40L (CD40L-WT) transfectant in cell-free supernatants. These studies suggest that gene transfer of the membrane-stable CD40L mutant into CD40-positive cells may provide an efficient and safe method to treat non-small cell lung cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811715", "endSection": "abstract" }, { "offsetInBeginSection": 34, "offsetInEndSection": 1143, "text": " (AITL) is a rare and aggressive neoplasm clinically characterized by sudden onset of constitutional symptoms, lymphadenopathy, hepatosplenomegaly, frequent autoimmune phenomena, particularly hemolytic anemia and thrombocytopenia, and polyclonal hypergammaglobulinemia. The lymph node histological picture is also distinctive, constituted by a polymorphic infiltrate, a marked proliferation of high endothelial venules, and a dense meshwork of dentritic cells. The neoplastic CD4+ T-cells represent a minority of the lymph node cell population; its detection is facilitated by the aberrant expression of CD10. Almost all cases arbor an EBV infected B-cell population. Patients with AITL have a poor prognosis with conventional treatment, with a median overall survival of less than 3 years. Patients achieving a good clinical response seem beneficiate from a consolidation with high-dose therapy and autologous stem cell transplantation. Constitutional symptoms and autoimmune phenomena, and some times also the neoplastic masses may respond to immunosuppressive or immunomodulatory agents such as thalidomide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18684638", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 1381, "text": "Survivin expression is a poor prognostic marker in a number of cancers. Clinical trials are currently underway evaluating anti-sense oligonucleotides against Survivin, immunotherapy using Survivin primed dentritic cells and peptide mimics that block interaction of Survivin with Hsp90 resulting in loss of Survivin protein stability. Additional approaches using ribozymes against Survivin mRNA, or dominant-negative cDNA to block Survivin function are in pre-clinical stages. Like many genes, Survivin is alternately spliced and a number of new splice variants have recently been identified. Expression of some of these splice variants correlates with loss of steroid receptors as well as the tumor suppressor p53, in some cancers, suggesting that like wild-type Survivin, at least some of these splice variants may also have prognostic relevance. This review will focus on the current understanding of the function of Survivin splice variants and their expression and sub-cellular localization in normal and neoplastic tissues as well as critically evaluating the potential toxicity of the Survivin directed therapies and their predicted effect on the alternatively spliced Survivin isoforms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17986000", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 965, "text": " Immunotherapy applying ex vivo-generated and tumor antigen-loaded dentritic cells has been successfully introduced in clinical vaccination protocols and has proven to be feasible and effective in some patients. A better understanding of how dentritic cells succeed to induce and modulate immunity is necessary to optimally exploit dentritic cells in anticancer vaccines. The authors will review novel insights in antigen loading, activation and migration of dentritic cells and their impact on the application of ex vivo-generated dentritic cell vaccines. In addition, novel means to exploit dentritic cells in cancer vaccines by loading and activation of dentritic cells directly in situ and possible obstacles that should be overcome to induce long-lasting immunity in therapeutic settings will be discussed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16221071", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of nemaline myopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17846275", "http://www.ncbi.nlm.nih.gov/pubmed/2213842", "http://www.ncbi.nlm.nih.gov/pubmed/15336686" ], "ideal_answer": [ "Nemaline myopathy has a autosomal dominant or recessive mode of inheritance." ], "exact_answer": [ "autosomal dominant", "autosomal recessive" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020512", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017696", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020914", "http://www.disease-ontology.org/api/metadata/DOID:423", "http://www.disease-ontology.org/api/metadata/DOID:3191" ], "type": "factoid", "id": "516be1d6298dcd4e5100006a", "snippets": [ { "offsetInBeginSection": 879, "offsetInEndSection": 1010, "text": "The results indicate that mutations in TPM2 may cause nemaline myopathy as well as cap disease with a dominant mode of inheritance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17846275", "endSection": "sections.0" }, { "offsetInBeginSection": 346, "offsetInEndSection": 435, "text": "Autosomal recessive inheritance had been verified or appeared likely in all nebulin cases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15336686", "endSection": "sections.0" }, { "offsetInBeginSection": 664, "offsetInEndSection": 850, "text": "Most cases were sporadic, but in addition there were instances of both autosomal dominant and autosomal recessive inheritance, while two families showed mosaicism for dominant mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15336686", "endSection": "sections.0" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1114, "text": "Finding the causative mutation(s) determines the mode of inheritance", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15336686", "endSection": "sections.0" }, { "offsetInBeginSection": 751, "offsetInEndSection": 967, "text": "We conclude that in the Finnish CNM patients, the mode of inheritance appears to be recessive. Apart from a few instances of dominant inheritance, most cases published also seem compatible with recessive inheritance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2213842", "endSection": "sections.0" } ] }, { "body": "Which syndrome is NHE6 associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "http://www.ncbi.nlm.nih.gov/pubmed/24035762", "http://www.ncbi.nlm.nih.gov/pubmed/25044251" ], "ideal_answer": [ "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia." ], "exact_answer": [ "Christianson syndrome" ], "type": "factoid", "id": "56d860ad51531f7e33000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 141, "text": "Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035762", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "OBJECTIVE: Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 170, "text": "encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" } ] }, { "body": "What is known about the reimbursement of Viagra", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20608882", "http://www.ncbi.nlm.nih.gov/pubmed/22554140", "http://www.ncbi.nlm.nih.gov/pubmed/10718038", "http://www.ncbi.nlm.nih.gov/pubmed/23231890", "http://www.ncbi.nlm.nih.gov/pubmed/12442853", "http://www.ncbi.nlm.nih.gov/pubmed/12119585", "http://www.ncbi.nlm.nih.gov/pubmed/14769012", "http://www.ncbi.nlm.nih.gov/pubmed/19715380", "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "http://www.ncbi.nlm.nih.gov/pubmed/10858175", "http://www.ncbi.nlm.nih.gov/pubmed/14769010", "http://www.ncbi.nlm.nih.gov/pubmed/16194131", "http://www.ncbi.nlm.nih.gov/pubmed/10345973" ], "ideal_answer": [ "Coverage of Viagra/Sildenafil for erectile dysfunction by health insurance plans is a contentious issue in developed countries. There are data of the limitations (6 per month) and co-payments (26.6%) by patients in the US.\nThe costs for Viagra/Sildenafil for PAH (pulmonary artery hypertension) appear to be covered by health insurances in the US." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059034", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059033", "http://www.biosemantics.org/jochem#4266960", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019458", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012943", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007356", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012052", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012051", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007357", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016527", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007350", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008329", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009310", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009313", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003365", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017281", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007345", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006278", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007341", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007342", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007348", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007349", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017048" ], "type": "summary", "id": "5150b45ad24251bc0500006f", "snippets": [ { "offsetInBeginSection": 887, "offsetInEndSection": 1031, "text": "Treatment with sildenafil was less costly and resulted in a greater gain in quality-adjusted life-years (QALYs) compared with other treatments. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715380", "endSection": "sections.0" }, { "offsetInBeginSection": 1214, "offsetInEndSection": 1329, "text": "Based on this model, sildenafil is a cost-effective treatment for PAH with a low price and a net increase in QALYs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715380", "endSection": "sections.0" }, { "offsetInBeginSection": 713, "offsetInEndSection": 917, "text": "Four treatment strategies, Viagra, Rivastigmine, statins, and lung transplants, are analysed with respect to whether either cost-effectiveness or need, or both, seem to have played a role in the decisions", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14769012", "endSection": "sections.0" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1246, "text": "it seems that decisions are almost exclusively made with reference to the principle of need.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14769012", "endSection": "sections.0" }, { "offsetInBeginSection": 128, "offsetInEndSection": 138, "text": "In Sweden ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14769012", "endSection": "sections.0" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1563, "text": "decisions on priority setting are almost solely based on the principle of need. This implies that the principle of cost-effectiveness is given very little space, which is a problem as this means an obvious risk of inefficient resource use.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14769012", "endSection": "sections.0" }, { "offsetInBeginSection": 530, "offsetInEndSection": 721, "text": "The case of Viagra, it concludes, holds out two general lessons: first, allow exceptions to total bans on reimbursement; second, involve the medical profession in the decision-making process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12442853", "endSection": "sections.0" }, { "offsetInBeginSection": 260, "offsetInEndSection": 377, "text": "This paper analyzes the rationing strategies adopted in four countries (United States, Britain, Germany, and Sweden),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12442853", "endSection": "sections.0" }, { "offsetInBeginSection": 44, "offsetInEndSection": 178, "text": "the question whether statutory social health insurances are obliged to reimburse the costs for the treatment of erectile dysfunction. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12119585", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 85, "text": "Coverage of sildenafil by health insurance plans is a contentious issue. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10858175", "endSection": "sections.0" }, { "offsetInBeginSection": 725, "offsetInEndSection": 983, "text": "coverage of Viagra and Zyban was limited predominantly through generalized exclusion or through restrictions on quantity or duration of use. Value judgments, rather than cost, seem to play a central, though largely unspoken, role in these coverage decisions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10718038", "endSection": "sections.0" }, { "offsetInBeginSection": 284, "offsetInEndSection": 486, "text": "availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "endSection": "sections.0" }, { "offsetInBeginSection": 2412, "offsetInEndSection": 2816, "text": "lthough the present study showed some variations between countries in selected indicators of availability and access to orphan drugs, virtually all of the drugs in question were available and accessible in our sample. However, substantial co-payments in the US and Canada represent important barriers to patient access, especially in the case of expensive treatments such as those analysed in this study.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "endSection": "sections.0" }, { "offsetInBeginSection": 223, "offsetInEndSection": 370, "text": "Adults with evidence of PAH from 1 January 2004 (commercial and Medicaid) or 1 July 2006 (Medicare Advantage) through 30 June 2008 were identified.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22554140", "endSection": "sections.0" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1236, "text": "Most patients (94%) initiated treatment with monotherapy (most commonly sildenafil or bosentan)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22554140", "endSection": "sections.0" }, { "offsetInBeginSection": 1659, "offsetInEndSection": 1761, "text": "Mean PAH-related healthcare costs were $6617 per patient per month, comprising 71% of all-cause costs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22554140", "endSection": "sections.0" }, { "offsetInBeginSection": 141, "offsetInEndSection": 278, "text": "Retrospective claims database analysis of 706 patients with PAH enrolled in a large, geographically diverse US managed-care organization.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20608882", "endSection": "sections.0" }, { "offsetInBeginSection": 1816, "offsetInEndSection": 2124, "text": "Of the oral agents approved for treating PAH at the time of this study, sildenafil was most commonly prescribed as index therapy and was also associated with the lowest costs, largely due to significantly lower pharmacy costs. This study is characterized by limitations inherent to claims database analyses, ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20608882", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 332, "text": "Erectile dysfunction (ED) affects approximately 30 million men in the United States. The objectives of this study were to (1) assess the cost and utilization of sildenafil citrate (Viagra), an oral therapeutic agent for ED, in a large managed care organization (MCO) with a quantity limit of 6 units per 30-day supply and", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16194131", "endSection": "sections.0" }, { "offsetInBeginSection": 1480, "offsetInEndSection": 2004, "text": "The total allowed charges for sildenafil pharmacy claims in 2001 were 3.56 million US dollars, of which patients paid 26.6% in average cost-share, and the net MCO cost per member per month (PMPM) was 0.18 US dollars. A total of 1,681 patients (8.3%) exceeded their quantity restrictions for sildenafil tablets in 2001, of which 1,362 (81.0%) paid cash and 319 (19.0%, or 1.6% of all sildenafil users) appealed and received approval from the MCO for additional sildenafil tablets beyond the restriction of 6 tablets per month", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16194131", "endSection": "sections.0" }, { "offsetInBeginSection": 2211, "offsetInEndSection": 2469, "text": "A quantity limit of 6 tablets of sildenafil per 30-day period was associated with a drug cost to users and the MCO of 0.25 US dollars PMPM. Sildenafil users paid an average cost-share of 26.6%, resulting in a net drug cost of 0.18 US dollars PMPM to the MCO.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16194131", "endSection": "sections.0" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1008, "text": "Managed care companies are expected to counter runaway pharmacy costs for sildenafil by excluding it from coverage, imposing significant limitations, or requiring higher copayments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10345973", "endSection": "sections.0" } ] }, { "body": "Why is lock mass used in Orbitrap measurements?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21133379", "http://www.ncbi.nlm.nih.gov/pubmed/22941912", "http://www.ncbi.nlm.nih.gov/pubmed/21953191", "http://www.ncbi.nlm.nih.gov/pubmed/16249172", "http://www.ncbi.nlm.nih.gov/pubmed/16478717" ], "ideal_answer": [ "The lock mass is a compound of known mass and is used to compensate for drifts in instrument calibration." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058" ], "type": "summary", "id": "530b01a6970c65fa6b000008", "snippets": [ { "offsetInBeginSection": 1060, "offsetInEndSection": 1123, "text": "Benzyldimethylphenylammonium was used as an internal lock mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22941912", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 409, "text": "To compensate for drifts in instrument calibration, a compound of known mass is often employed. This 'lock mass' provides an internal mass standard in every spectrum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953191", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 569, "text": "The use of mass calibrants (lock masses) to reduce the systematic error of mass-to-charge measurements has also been reported and, in some cases, incorporated in the instrument control software by the instrument manufacturers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21133379", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 845, "text": "We achieved absolute mass accuracies for intact proteins between 0.92 and 2.8 ppm using the \"lock mass\" mode of operation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16478717", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 772, "text": "Real time recalibration on the \"lock mass\" by corrections of mass shift removes mass error associated with calibration of the mass scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16249172", "endSection": "abstract" } ] }, { "body": "Which virus is Cidofovir (Vistide) indicated for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19725597", "http://www.ncbi.nlm.nih.gov/pubmed/9814660", "http://www.ncbi.nlm.nih.gov/pubmed/11772283", "http://www.ncbi.nlm.nih.gov/pubmed/11154213" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10493715", "o": "RXNORM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10493715", "o": "Cidofovir Injectable Solution" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1251348", "o": "http://linkedlifedata.com/resource/umls/label/A10493715" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1251348", "o": "http://linkedlifedata.com/resource/umls/label/A10493715" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10493715", "o": "377136" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1236858", "o": "http://linkedlifedata.com/resource/umls/id/C1251348" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1236858", "o": "http://linkedlifedata.com/resource/umls/label/A10660704" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10660704", "o": "Cidofovir Injectable Solution [Vistide]" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10660704", "o": "362931" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1751684", "o": "J0740" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1751684", "o": "INJECTION, CIDOFOVIR, 375 MG" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0520139", "o": "http://linkedlifedata.com/resource/umls/label/A1751684" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10418206", "o": "RXNORM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0984907", "o": "http://linkedlifedata.com/resource/umls/label/A10418206" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10418206", "o": "Cidofovir 75 MG/ML" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A1751684", "o": "HCPCS" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10725904", "o": "571699" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1605899", "o": "http://linkedlifedata.com/resource/umls/label/A10725904" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10725904", "o": "Cidofovir 75 MG/ML [Vistide]" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10660704", "o": "RXNORM" } ], "ideal_answer": [ "Cidofovir is commonly used in the treatment of cytomegalovirus (CMV) infection and disease." ], "exact_answer": [ "cytomegalovirus" ], "concepts": [ "http://www.biosemantics.org/jochem#4236374", "http://www.biosemantics.org/jochem#4261248" ], "type": "factoid", "id": "52bf1cad03868f1b0600000a", "snippets": [ { "offsetInBeginSection": 326, "offsetInEndSection": 457, "text": "Currently, there are four antivirals available that are active against CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19725597", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 731, "text": "At present, the antiviral drugs ganciclovir, foscarnet and cidofovir are commonly used in the treatment of CMV infection and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772283", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1360, "text": "Cidofovir can be considered as second-line therapy in patients with CMV disease failing previous antiviral therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154213", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1128, "text": "dditional drugs like lobucavir and cidofovir have been used for specific indications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9814660", "endSection": "abstract" } ] }, { "body": "Have gnotobiotic animal models been used for the study of bowel disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17145736", "http://www.ncbi.nlm.nih.gov/pubmed/11984521", "http://www.ncbi.nlm.nih.gov/pubmed/20004202", "http://www.ncbi.nlm.nih.gov/pubmed/24500617", "http://www.ncbi.nlm.nih.gov/pubmed/18841702", "http://www.ncbi.nlm.nih.gov/pubmed/24959425", "http://www.ncbi.nlm.nih.gov/pubmed/16127016", "http://www.ncbi.nlm.nih.gov/pubmed/16954804", "http://www.ncbi.nlm.nih.gov/pubmed/21426337", "http://www.ncbi.nlm.nih.gov/pubmed/21278760", "http://www.ncbi.nlm.nih.gov/pubmed/12906096", "http://www.ncbi.nlm.nih.gov/pubmed/2765093" ], "ideal_answer": [ "Yes, gnotobiotic animals (e.g. mice) have been used for the study of bowel disease (e.g. inflammatory bowel disease)." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13419", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003424", "http://www.disease-ontology.org/api/metadata/DOID:5143", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043183", "http://www.disease-ontology.org/api/metadata/DOID:6880", "http://www.disease-ontology.org/api/metadata/DOID:0050589", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055496", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058535", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015212", "http://www.disease-ontology.org/api/metadata/DOID:8778" ], "type": "yesno", "id": "56f12ca92ac5ed145900000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains: common patterns and bacteria strain specific signatures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16954804", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 372, "text": " Specific pathogen-free (SPF), but not germfree (GF), interleukin (IL)-2-deficient (IL-2-/-) mice develop inflammatory bowel disease (IBD) at 10 to 15 weeks of age. Gnotobiotic IL-2-/- mice monocolonized with E. coli mpk develop IBD at 25 to 33 weeks of age but not B. vulgatus mpk, E. coli Nissle 1917, or mice cocolonized with both E. coli mpk and B. vulgatus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16954804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Lactobacillus reuteri promotes Helicobacter hepaticus-associated typhlocolitis in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426337", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 517, "text": "To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice. No typhlocolitis developed in germ-free controls (n=21) or in L. reuteri (n=8) or H. hepaticus (n=18) mono-associated mice for 20 weeks post-infection. As positive controls, three specific pathogen-free IL-10(-/-) mice dosed with H. hepaticus developed severe typhlocolitis within 11 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426337", "endSection": "abstract" }, { "offsetInBeginSection": 1597, "offsetInEndSection": 1787, "text": "These data support that the development of typhlocolitis in H. hepaticus-infected IL-10(-/-) mice required co-colonization with other microbiota and in this study, required only L. reuteri. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426337", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1305, "text": "When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24500617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21278760", "endSection": "title" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1279, "text": "The immunomodulatory effects of microbiota and probiotics for inflammatory bowel diseases and the role of bacteria in their etiologies are being studied in gnotobiotic systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18841702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426337", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1153, "text": "Gnotobiotic piglets may be used as a suitable animal model to study colitis induced by C. jejuni", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2765093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21278760", "endSection": "title" }, { "offsetInBeginSection": 404, "offsetInEndSection": 720, "text": "We investigated the changes in renal expression of Kl as a consequence of colitis. METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20004202", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 720, "text": "METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20004202", "endSection": "abstract" } ] }, { "body": "List chromosomes that have been linked to Arnold Chiari syndrome in the literature.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15742475", "http://www.ncbi.nlm.nih.gov/pubmed/2798270", "http://www.ncbi.nlm.nih.gov/pubmed/24359474", "http://www.ncbi.nlm.nih.gov/pubmed/324229", "http://www.ncbi.nlm.nih.gov/pubmed/17103432", "http://www.ncbi.nlm.nih.gov/pubmed/23620759", "http://www.ncbi.nlm.nih.gov/pubmed/20101707", "http://www.ncbi.nlm.nih.gov/pubmed/6548367", "http://www.ncbi.nlm.nih.gov/pubmed/2130777", "http://www.ncbi.nlm.nih.gov/pubmed/20571508", "http://www.ncbi.nlm.nih.gov/pubmed/11754060", "http://www.ncbi.nlm.nih.gov/pubmed/23476832", "http://www.ncbi.nlm.nih.gov/pubmed/23942271", "http://www.ncbi.nlm.nih.gov/pubmed/17190989" ], "ideal_answer": [ "Chromosomes 1, 3, 5, 6, 8, 9, 12, 13, 15, 16, 18, 22, X and Y have been reported in association with Arnold Chiari syndrome in genetic linkage studies and individual case reports." ], "exact_answer": [ [ "1" ], [ "3" ], [ "5" ], [ "6" ], [ "8" ], [ "9" ], [ "12" ], [ "13" ], [ "15" ], [ "16" ], [ "18" ], [ "22" ], [ "X" ], [ "Y" ] ], "type": "list", "id": "54d77bdf3706e89528000019", "snippets": [ { "offsetInBeginSection": 920, "offsetInEndSection": 1247, "text": "Consistent with a genetic hypothesis for CMI, much of the PF morphology was found to be heritable and multiple genomic regions were strongly implicated from OSA, including regions on Chromosomes 1 (LOD = 3.07, p = 3 \u00d7 10(-3) ) and 22 (LOD = 3.45, p = 6 \u00d7 10(-5) ) containing several candidates warranting further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24359474", "endSection": "abstract" }, { "offsetInBeginSection": 2057, "offsetInEndSection": 2206, "text": "Furthermore, we report the first case of documented Arnold-Chiari malformation type I and increased factor XIII activity associated with 6p trisomy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942271", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1506, "text": "Of particular interest were two regions (Chr8, Max LOD\u200a=\u200a3.04; Chr12, Max LOD\u200a=\u200a2.09) identified within the subset of \"CTD-negative\" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23620759", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 766, "text": "Moreover, the performed DNA analysis showed interstitial duplication in chromosome 5 (5q35.1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23476832", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 774, "text": "CGH microarray showed a approximately 520.7 kb microdeletion on 16p13.3 involving CREBBP, ADCY9, and SRL genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20101707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Pentasomy 49,XXXXY associated with a Chiari type 1 malformation and cervical syrinx.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17190989", "endSection": "title" }, { "offsetInBeginSection": 312, "offsetInEndSection": 431, "text": "A 13-year-old with pentasomy 49,XXXXY and a Chiari type 1 malformation with an associated cervical syrinx is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17190989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Phenotypic definition of Chiari type I malformation coupled with high-density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103432", "endSection": "title" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1101, "text": "Two-point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1-22.3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103432", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1516, "text": "Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33-33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103432", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 1032, "text": "In addition, this child had an Arnold-Chiari type I malformation that required surgical decompression. FISH studies using BAC clones spanning the 5q15 to 5q22 region revealed that these were all present in both homologues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15742475", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 448, "text": "The karyotype showed 46, XY, del(1)(q23q31.2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11754060", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1091, "text": "Karyotype analysis showed inversion of Y chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2130777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 557, "text": "The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male:female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2798270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "An unusual heterotopia of striated skeletal muscle and glial tissue occurred in the pontine meninges of a stillborn male showing feature of trisomy 13 and an Arnold-Chiari malformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6548367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Type II Arnold-Chiari malformation with normal spine in trisomy 18.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/324229", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "A variety of anomalies of the central nervous system are observed in trisomy 18. The present case describes an infant having a type II Arnold-Chiari malformation without spina bifida. One previous case of an Arnold-Chiari malformation was reported in trisomy 18 but that infant also had a lumbar meningomyelocoele. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/324229", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 806, "text": "Recently, a child was reported who presented with a 3p13-14.1 deletion of four genes, including FOXP1, and a constellation of deficits that included speech delay. In this study, we report the case of a patient with a single deletion of FOXP1. This patient presented with speech and motor developmental delays, a Chiari I malformation, and epileptiform discharges.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20571508", "endSection": "abstract" } ] }, { "body": "Which translocation is the hallmark of Ewing sarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22266186", "http://www.ncbi.nlm.nih.gov/pubmed/10030577", "http://www.ncbi.nlm.nih.gov/pubmed/24974828", "http://www.ncbi.nlm.nih.gov/pubmed/24124617", "http://www.ncbi.nlm.nih.gov/pubmed/22742646", "http://www.ncbi.nlm.nih.gov/pubmed/23145994", "http://www.ncbi.nlm.nih.gov/pubmed/16864960", "http://www.ncbi.nlm.nih.gov/pubmed/21942527", "http://www.ncbi.nlm.nih.gov/pubmed/16083345", "http://www.ncbi.nlm.nih.gov/pubmed/15919668", "http://www.ncbi.nlm.nih.gov/pubmed/21653923", "http://www.ncbi.nlm.nih.gov/pubmed/18971581", "http://www.ncbi.nlm.nih.gov/pubmed/15274413", "http://www.ncbi.nlm.nih.gov/pubmed/6416622", "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "http://www.ncbi.nlm.nih.gov/pubmed/22240531", "http://www.ncbi.nlm.nih.gov/pubmed/8644855", "http://www.ncbi.nlm.nih.gov/pubmed/21422656" ], "ideal_answer": [ "Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients", "The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24;12), is detected in 95% of Ewing sarcoma patients.", "The hallmark of Ewing s sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene " ], "exact_answer": [ "translocation t(11;22) (q24;12)" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3368", "http://www.disease-ontology.org/api/metadata/DOID:4232", "http://www.disease-ontology.org/api/metadata/DOID:4980", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512" ], "type": "factoid", "id": "552faababc4f83e828000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24124617", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 199, "text": "Ewing's sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23145994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The hallmark of Ewing's sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22742646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The chromosomal translocation t(11;22)(q24;q12) yields the EWS-Fli1 fusion gene, which contributes to the development of Ewing Family Tumors (EFTs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266186", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 82, "text": "Ewing sarcoma is extremely rare in people from East and Southeast Asia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22240531", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1141, "text": "The t(11;22)(q24:q12) translocation was present in all patients in our series", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22240531", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1318, "text": "We confirmed that distant metastases is highly predictive of a poor outcome, and that the t(11;22)(q24:q12) translocation was present in all patients in our series", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22240531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "The genetic hallmark of the Ewing sarcoma family of tumours (ESFT) is the presence of the t(11;22)(q24;q12) translocation, present in up to 85% of cases of ESFT, which creates the EWS/FLI1 fusion gene and results in the expression of a chimeric protein regulating many other genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16083345", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 424, "text": "Ewing sarcoma family of tumors (ESFTs) are characterized by the t(11;22)(q24;q12) translocation that generates the Ewing sarcoma breakpoint region 1 and Friend leukemia virus integration 1 (EWS-FLI1) fusion transcription factor responsible for the highly malignant phenotype of this tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21653923", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 770, "text": "The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21422656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Translocation of chromosomes 11 and 22 in choroidal metastatic Ewing sarcoma detected by fluorescent in situ hybridization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10030577", "endSection": "title" }, { "offsetInBeginSection": 632, "offsetInEndSection": 778, "text": "Molecular detection of the t(11;22)(q24;q12) translocation in Ewing sarcoma is valuable in the differential diagnosis of small round cell tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10030577", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 818, "text": "This patient illustrates the second reported occurrence of primary Ewing sarcoma in the stomach and the first reported with the t(11;22)(q24;q12) gene translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971581", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Translocations involving ETS-transcription factors, most commonly leading to the EWSR1-FLI1 fusion protein, are the hallmark of Ewing sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24974828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "EWS-Fli1, a fusion gene resulting from a chromosomal translocation t(11;22, q24;q12) and found in Ewing sarcoma and primitive neuroectodermal tumors, encodes a transcriptional activator and promotes cellular transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15919668", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 957, "text": "The presence of the t(11;22)(q24;ql2) translocation should probably not be considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor in the absence of supporting histological evidence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8644855", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 417, "text": "Ewing sarcoma is the prototypical member of this group of sarcomas; it was the first to be recognized pathologically as a singular entity and to have its signature translocation defined cytogenetically, which led to the identification of its key driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, chimeric transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21942527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The hallmark of Ewings sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22742646", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 437, "text": "Ewing sarcoma family of tumors (ESFTs) are characterized by the t(11;22)(q24;q12) translocation that generates the Ewing sarcoma breakpoint region 1 and Friend leukemia virus integration 1 (EWS-FLI1) fusion transcription factor responsible for the highly malignant phenotype of this tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21653923", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 823, "text": "This patient illustrates the second reported occurrence of primary Ewing sarcoma in the stomach and the first reported with the t(11;22)(q24;q12) gene translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971581", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 445, "text": "Diagnosis is based on history, immunostaining with at least 2 neural markers, ultrastructural examination, and evidence of an abnormal t(11;22)(q24;q12) translocation as the hallmark for the Ewing's sarcoma family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15274413", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 562, "text": "The translocation results in the fusion of the EWS gene with the transcription factor gene FLI1 which has been considered a hallmark of ESFT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16864960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "[Chromosomal translocation (11; 22) in cell lines of Ewing's sarcoma].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6416622", "endSection": "title" }, { "offsetInBeginSection": 187, "offsetInEndSection": 409, "text": "These results, associated with those obtained at the same time and independently from fresh tumor cells, suggest that the translocation t(11; 22)(q24; q12) may be a chromosomal marker characteristic of Ewing sarcoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6416622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 444, "text": "Diagnosis is based on history, immunostaining with at least 2 neural markers, ultrastructural examination, and evidence of an abnormal t(11;22)(q24;q12) translocation as the hallmark for the Ewing's sarcoma family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15274413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Translocations involving ETS-transcription factors, most commonly leading to the EWSR1-FLI1 fusion protein, are the hallmark of Ewing sarcoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24974828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "The genetic hallmark of the Ewing sarcoma family of tumours (ESFT) is the presence of the t(11;22)(q24;q12) translocation, present in up to 85% of cases of ESFT, which creates the EWS/FLI1 fusion gene and results in the expression of a chimeric protein regulating many other genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16083345", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 561, "text": "The translocation results in the fusion of the EWS gene with the transcription factor gene FLI1 which has been considered a hallmark of ESFT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16864960", "endSection": "abstract" } ] }, { "body": "Is invasion and metastasis one of the hallmarks of cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19662202" ], "ideal_answer": [ "Yes, invasion and metastasis are one of the so-called hallmarks of cancer." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009362", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009361", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369" ], "type": "yesno", "id": "5316d4fcb166e2b806000005", "snippets": [ { "offsetInBeginSection": 258, "offsetInEndSection": 601, "text": "The pathogenesis of MM involves the accumulation of extensive cytogenetic changes, as well as cancer-related phenotypic alterations that facilitate tumor cell survival, invasion and metastasis. This review presents current knowledge regarding the biological characteristics of this disease that are linked to the so-called hallmarks of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19662202", "endSection": "abstract" } ] }, { "body": "Is it possible to detect survivin protein expression in normal human adult tissues?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22930255", "http://www.ncbi.nlm.nih.gov/pubmed/14719083", "http://www.ncbi.nlm.nih.gov/pubmed/18425079", "http://www.ncbi.nlm.nih.gov/pubmed/16360419", "http://www.ncbi.nlm.nih.gov/pubmed/18376799", "http://www.ncbi.nlm.nih.gov/pubmed/17382535", "http://www.ncbi.nlm.nih.gov/pubmed/15195112", "http://www.ncbi.nlm.nih.gov/pubmed/15990723", "http://www.ncbi.nlm.nih.gov/pubmed/18856066", "http://www.ncbi.nlm.nih.gov/pubmed/12671708", "http://www.ncbi.nlm.nih.gov/pubmed/15138808", "http://www.ncbi.nlm.nih.gov/pubmed/17611626", "http://www.ncbi.nlm.nih.gov/pubmed/17204284", "http://www.ncbi.nlm.nih.gov/pubmed/17163847", "http://www.ncbi.nlm.nih.gov/pubmed/23132836", "http://www.ncbi.nlm.nih.gov/pubmed/20520718", "http://www.ncbi.nlm.nih.gov/pubmed/16619249", "http://www.ncbi.nlm.nih.gov/pubmed/21371446", "http://www.ncbi.nlm.nih.gov/pubmed/20514400", "http://www.ncbi.nlm.nih.gov/pubmed/10626797" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10780389", "o": "Survivin" } ], "ideal_answer": [ "No. Survivin is an inhibitor of apoptosis that is undetectable in normal differentiated tissues of adult human.", "Most normal adult tissues do not express survivin, thymus and testis are the only exceptions." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014024", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0048729", "http://www.uniprot.org/uniprot/BIRC5_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0009888", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801" ], "type": "yesno", "id": "51680a49298dcd4e51000062", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Survivin (BIRC5) is one of the members of IAP-family apoptosis inhibitors. The BIRCS gene is expressed in most human embryonic tissues and malignant tumors but not in normal differentiated tissues of adult human.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18856066", "endSection": "sections.0" }, { "offsetInBeginSection": 177, "offsetInEndSection": 399, "text": "Survivin is an inhibitor of apoptosis that is undetectable in most terminally differentiated normal human tissues, strongly expressed in embryonic and fetal organs and is strongly expressed in many different human cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18425079", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Survivin is a member of the inhibitor apoptosis family that is overexpressed in many malignancies. It has five known alternative splice forms, some of which differ in their antiapoptotic properties and expression levels in human cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17204284", "endSection": "sections.0" }, { "offsetInBeginSection": 400, "offsetInEndSection": 458, "text": "survivin is usually not expressed in normal adult tissues,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16360419", "endSection": "sections.0" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1409, "text": "AZD1152-hQPA induced caspase-dependent apoptosis of some cell lines, demonstrated by loss of mitochondrial membrane potential, activation of caspase-9, followed by activation of caspase-3. This effect was accompanied by the inhibition of survivin expression. In vivo efficacy was determined in NOD/SCID/\u03b3c(null) mice implanted with the Ramos human BL cell line. AZD1152 had anti-tumour effects in this murine xenograft model. There preclinical data suggest that the inhibition of Aurora B kinase is a potentially useful therapeutic strategy in BL and HL.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21371446", "endSection": "sections.0" }, { "offsetInBeginSection": 10, "offsetInEndSection": 469, "text": "a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10626797", "endSection": "sections.0" }, { "offsetInBeginSection": 630, "offsetInEndSection": 1193, "text": "Further comparison of the distribution of PDEF with other widely recognized cancer-associated molecules showed that PDEF has more restricted distributions than Her-2/neu, Bcl-2, survivin or telomerase in cDNA libraries from normal human tissues and more increased distribution than Her-2/neu, CA-125, Bcl-2, survivin and telomerase in cDNA libraries from brain (except survivin), breast, lung and ovarian tumors. These data together show a better tumor-association for PDEF and suggest that PDEF is a more suitable target for developing specific cancer therapies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14719083", "endSection": "sections.0" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1750, "text": "we identified decreased FHIT expression resulting in apoptosis inhibition and decreasing apoptosis associated with abnormal levels of some pro- and anti-apoptotic proteins (Bax, Bcl-2 and Survivin) by TUNEL and TMA. Our results demonstrated that the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT, inactivated specifically in human CRC, and contributes to our understanding of the mechanism of colorectal carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17382535", "endSection": "sections.0" } ] }, { "body": "List symptoms of Meigs' Syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24962423", "http://www.ncbi.nlm.nih.gov/pubmed/23328144", "http://www.ncbi.nlm.nih.gov/pubmed/25469326", "http://www.ncbi.nlm.nih.gov/pubmed/24490014", "http://www.ncbi.nlm.nih.gov/pubmed/26046039" ], "ideal_answer": [ "Meigs' syndrome is a benign ovarian tumor associated with ascites and pleural effusion." ], "exact_answer": [ [ "benign ovarian tumor" ], [ "ascites" ], [ "pleural effusion" ] ], "type": "list", "id": "56be0a18ef6e394741000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Meigs' syndrome is a benign ovarian tumor associated with ascites and pleural effusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26046039", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 1030, "text": "Although postmenopausal women with ovarian tumor, ascites, pleural effusion, and elevation of CA-125 levels probably have malignant ovarian tumors, Meigs' syndrome must be considered in the differential diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26046039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND: The Demons-Meigs syndrome should usually be evoked in case of presence of a typical triad: abdominopelvic mass, ascites and hydrothorax. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25469326", "endSection": "abstract" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1109, "text": "CONCLUSION: Meigs' syndrome should be considered at the differential diagnosis for a patient with pelvic mass, pleural effusion and ascites with normal cytology, increased CA125 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24490014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND: The Meigs' syndrome is a rare but well-known syndrome defined as the triad of benign solid ovarian tumor, ascites, and pleural effusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24962423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Ovarian mass, pleural effusion, and ascites: revisiting Meigs syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328144", "endSection": "title" }, { "offsetInBeginSection": 198, "offsetInEndSection": 306, "text": "When benign ovarian fibroma is associated with ascites and/or pleural effusion it is termed Meigs syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Ovarian mass, pleural effusion, and ascites: revisiting Meigs syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328144", "endSection": "title" } ] }, { "body": "What is the effect of CRD-BP on the stability of c-myc mRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17264115", "http://www.ncbi.nlm.nih.gov/pubmed/16778892", "http://www.ncbi.nlm.nih.gov/pubmed/11745432", "http://www.ncbi.nlm.nih.gov/pubmed/10692488", "http://www.ncbi.nlm.nih.gov/pubmed/12024010", "http://www.ncbi.nlm.nih.gov/pubmed/10850408", "http://www.ncbi.nlm.nih.gov/pubmed/9178888", "http://www.ncbi.nlm.nih.gov/pubmed/9801297", "http://www.ncbi.nlm.nih.gov/pubmed/12894594" ], "ideal_answer": [ "The c-myc mRNA coding region determinant-binding protein (CRD-BP) has high affinity for the coding region determinant (CRD) of c-myc mRNA. Such affinity is believed to protect c-myc CRD from endonucleolytic attack.", "The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance " ], "exact_answer": [ "To protect c-myc CRD from endonucleolytic attack." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043488", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070937", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070934", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048255" ], "type": "factoid", "id": "55390901bc4f83e828000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a mammalian endoribonuclease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17264115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The c-myc mRNA coding region determinant-binding protein (CRD-BP) has high affinity for the coding region determinant (CRD) of c-myc mRNA. Such affinity is believed to protect c-myc CRD from endonucleolytic attack", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17264115", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1192, "text": " These results provide the first direct evidence that CRD-BP can indeed protect c-myc CRD cleavage initiated by an endoribonuclease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17264115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12894594", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "The Coding Region Determinant-Binding Protein (CRD-BP) is an RRM and KH-domain-containing protein that recognizes specifically at least three RNAs. It binds to one of the two c-myc mRNA instability elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12894594", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 402, "text": "CRD-BP has been assigned a role in stabilizing c-myc mRNA by preventing its endonucleolytic cleavage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12894594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "A 249-nucleotide coding region instability determinant (CRD) destabilizes c-myc mRNA. Previous experiments identified a CRD-binding protein (CRD-BP) that appears to protect the CRD from endonuclease cleavage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12024010", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1118, "text": "These data suggest that c-myc mRNA is rapidly degraded unless it is (i) translated without pausing or (ii) protected by the CRD-BP when pausing occurs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12024010", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 303, "text": "Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11745432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10850408", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 521, "text": "Two regions within c- myc mRNA determine its short half-life. One is in the 3'-untranslated region, the other is in the coding region. A cytoplasmic protein, the coding region determinant-binding protein (CRD-BP), binds in vitro to the c- myc coding region instability determinant. We have proposed that the CRD-BP, when bound to the mRNA, shields the mRNA from endonucleolytic attack and thereby prolongs the mRNA half-life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9801297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9178888", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "We previously isolated and characterized a coding region determinant-binding protein (CRD-BP) that might regulate c-myc mRNA post-transcriptionally", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9178888", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 296, "text": "CRD-BP binds specifically to the coding region of c-myc mRNA and might stabilize c-myc mRNA in vitro by protecting it from endonucleolytic cleavage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9178888", "endSection": "abstract" } ] }, { "body": "What is the molecular function of psoralen photobinding on DNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1432387", "http://www.ncbi.nlm.nih.gov/pubmed/23416947", "http://www.ncbi.nlm.nih.gov/pubmed/10075890", "http://www.ncbi.nlm.nih.gov/pubmed/1821628", "http://www.ncbi.nlm.nih.gov/pubmed/20685815", "http://www.ncbi.nlm.nih.gov/pubmed/3273186", "http://www.ncbi.nlm.nih.gov/pubmed/1445915", "http://www.ncbi.nlm.nih.gov/pubmed/6504703", "http://www.ncbi.nlm.nih.gov/pubmed/367436" ], "ideal_answer": [ "The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix." ], "exact_answer": [ "It intercalates into the double helix." ], "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4272414", "http://www.biosemantics.org/jochem#4272414", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247" ], "type": "factoid", "id": "56c341acfedd0b786b000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6504703", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 380, "text": "Both compounds bind very efficiently to DNA, the extent of this process being modulated by the nature of substituents at position 8", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1432387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "We have described an exonuclease III/photoreversal procedure to map, with base pair resolution, the bases which have photoreacted with 4,5',8-trimethylpsoralen (Me3-psoralen) forming either monoadducts or interstrand cross-links in DNA (20)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3273186", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 382, "text": "Psoralen and light treatment removed negative superhelical turns, and extensive treatments failed to produce positive superhelical turns in covalently closed plasmid DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/367436", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 599, "text": "Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1821628", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 601, "text": "The crystal and molecular structure of 4,4',5'-trimethylazapsoralen, obtained by X ray diffraction, was also reported. Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1821628", "endSection": "abstract" } ] }, { "body": "Is progesterone effective for treatment of patients with traumatic brain injury based on clinical trial data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17327733", "http://www.ncbi.nlm.nih.gov/pubmed/19318112", "http://www.ncbi.nlm.nih.gov/pubmed/23326789", "http://www.ncbi.nlm.nih.gov/pubmed/17418038", "http://www.ncbi.nlm.nih.gov/pubmed/18447940", "http://www.ncbi.nlm.nih.gov/pubmed/19401954", "http://www.ncbi.nlm.nih.gov/pubmed/22033509", "http://www.ncbi.nlm.nih.gov/pubmed/24241345", "http://www.ncbi.nlm.nih.gov/pubmed/19660659", "http://www.ncbi.nlm.nih.gov/pubmed/17011666", "http://www.ncbi.nlm.nih.gov/pubmed/22570859", "http://www.ncbi.nlm.nih.gov/pubmed/25493974", "http://www.ncbi.nlm.nih.gov/pubmed/21249708", "http://www.ncbi.nlm.nih.gov/pubmed/25493978", "http://www.ncbi.nlm.nih.gov/pubmed/23076947", "http://www.ncbi.nlm.nih.gov/pubmed/18522765", "http://www.ncbi.nlm.nih.gov/pubmed/17933428", "http://www.ncbi.nlm.nih.gov/pubmed/22626570", "http://www.ncbi.nlm.nih.gov/pubmed/22668124", "http://www.ncbi.nlm.nih.gov/pubmed/24900479", "http://www.ncbi.nlm.nih.gov/pubmed/20486864", "http://www.ncbi.nlm.nih.gov/pubmed/23871679", "http://www.ncbi.nlm.nih.gov/pubmed/22300914", "http://www.ncbi.nlm.nih.gov/pubmed/17588708", "http://www.ncbi.nlm.nih.gov/pubmed/24205899", "http://www.ncbi.nlm.nih.gov/pubmed/19394357", "http://www.ncbi.nlm.nih.gov/pubmed/21497181" ], "ideal_answer": [ "No. Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. However, a recent large clinical trial showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials." ], "exact_answer": "no", "concepts": [ "http://www.biosemantics.org/jochem#4271493" ], "type": "yesno", "id": "54cf48acf693c3b16b00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND: Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25493978", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1583, "text": "The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo. CONCLUSIONS: Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25493978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25493974", "endSection": "abstract" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 1869, "text": "There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P=0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25493974", "endSection": "abstract" }, { "offsetInBeginSection": 1950, "offsetInEndSection": 2094, "text": "CONCLUSIONS: This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25493974", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 693, "text": "Numerous studies, however, show that progesterone has substantial pleiotropic properties as a neuroprotective agent in both animal models and humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24241345", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 1190, "text": "RESULTS: There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period (50% vs. 21%); subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5-8 (p=0.03). CONCLUSION: The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury, especially those with 5\u2264GCS\u22648, providing a potential benefit to the treatment of acute severe TBI patients. Considering this drug had no significant side effects, so progesterone could be used in patients with severe TBI as a neuro-protective drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23871679", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1283, "text": "While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22668124", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1793, "text": " All three studies reported the effects of progesterone on mortality. The pooled risk ratio (RR) for mortality at end of follow-up was 0.61, 95% confidence interval (CI) 0.40 to 0.93. Three studies measured disability and found the RR of death or severe disability in patients treated with progesterone to be 0.77, 95% CI 0.62 to 0.96.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23076947", "endSection": "abstract" }, { "offsetInBeginSection": 2161, "offsetInEndSection": 2418, "text": "AUTHORS' CONCLUSIONS: Current clinical evidence from three small RCTs indicates progesterone may improve the neurologic outcome of patients suffering TBI. This evidence is still insufficient and further multicentre randomised controlled trials are required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23076947", "endSection": "abstract" }, { "offsetInBeginSection": 1438, "offsetInEndSection": 1976, "text": "GOS was classified to 2 main categories of favorable and unfavorable recovery, of which, favorable recovery in placebo, progesterone, and progesterone-vitamin D was 25%, 45%, and 60%, respectively which showed a statistical significant difference among the groups (P-value = 0.03). CONCLUSION: The results showed that recovery rate in patients with severe brain trauma in the group receiving progesterone and vitamin D together was significantly higher than that of progesterone group, which was in turn higher than that of placebo group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326789", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1575, "text": " The pooled relative risk (RR) for mortality at end of follow-up is 0.61, 95% confidence interval (CI) 0.40 to 0.93. Three studies measured disability and found the RR of death or severe disability in patients treated with progesterone was 0.77, 95% confidence interval (CI) 0.62 to 0.96.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249708", "endSection": "abstract" }, { "offsetInBeginSection": 1774, "offsetInEndSection": 2031, "text": "AUTHORS' CONCLUSIONS: Current clinical evidence from three small RCTs indicates progesterone may improve the neurologic outcome of patients suffering TBI. This evidence is still insufficient and further multicentre randomised controlled trials are required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249708", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 633, "text": "Clinical trials have shown that short-and long-term progesterone treatment induces a significant improvement in the level of disability among patients with brain injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19318112", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 142, "text": "Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18447940", "endSection": "title" }, { "offsetInBeginSection": 701, "offsetInEndSection": 998, "text": "CONCLUSION: Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18447940", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1814, "text": "The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up (P < 0.05 and P < 0.01). The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up (P < 0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18447940", "endSection": "abstract" }, { "offsetInBeginSection": 2139, "offsetInEndSection": 2436, "text": "CONCLUSION: Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18447940", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 632, "text": "These data, combined with the results of the previously published ProTECT trial, show progesterone to be safe and potentially efficacious in the treatment of TBI. Larger phase III trials will be necessary to verify results prior to clinical implementation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18522765", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1649, "text": "CONCLUSION: It indicated that successive early application of PG will benefit the patients with acute severe head injury by improving the recovery and reducing the disability, which may be related to its alleviating inflammatory and lipid peroxidation response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17418038", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1508, "text": "Adverse and serious adverse event rates were similar in both groups, except that patients randomized to progesterone had a lower 30-day mortality rate than controls (rate ratio 0.43; 95% confidence interval 0.18 to 0.99). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17011666", "endSection": "abstract" }, { "offsetInBeginSection": 1690, "offsetInEndSection": 1963, "text": "However, moderate traumatic brain injury survivors who received progesterone were more likely to have a moderate to good outcome than those randomized to placebo. CONCLUSION: In this small study, progesterone caused no discernible harm and showed possible signs of benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17011666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900479", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 763, "text": "A US National Institutes of Health-sponsored, nationwide Phase III clinical trial is now evaluating progesterone for moderate-to-severe TBI in 1200 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033509", "endSection": "abstract" }, { "offsetInBeginSection": 765, "offsetInEndSection": 921, "text": "An industry-sponsored Phase III international trial is also under way, and planning for a trial using progesterone to treat pediatric brain injury has begun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19394357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900479", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1248, "text": "RESULTS: Analysis of these reviews yielded meanfuling observations: (1) The effectiveness of most ordinary treatments in TBI is inconclusive except that corticosteroids are likely to be ineffective or harmful, and tranexamic acid, nimodipine and progesterone show a promising effect in bleeding trauma, traumatic subarachnoid hemorrhage, TBI or severe TBI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22300914", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 387, "text": "Laboratory data strongly show that progesterone treatment after TBI reduces edema, improves outcomes, and restores blood-brain barrier function. Clinical studies to date agree with these data, and there are ongoing human trials for progesterone treatment after TBI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19401954", "endSection": "abstract" } ] }, { "body": "Is there a role for the cylindromatosis tumor suppressor (CYLD) in lung cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "http://www.ncbi.nlm.nih.gov/pubmed/22017589" ], "ideal_answer": [ "To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF - B activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF - B activity. Cyld encodes a 956-amino acid deubiquitinating enzyme, which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 mice ) using a conditional approach. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer. ", "To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF - B activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B activity. Cyld encodes a 956-amino acid deubiquitinating enzyme, which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 mice ) using a conditional approach. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer. ", "Yes. Down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. Fibroblasts from Cyld(Delta 9/Delta 9) embryos had hyperactive nuclear factor kappaB and c-Jun kinase pathways compared with control fibroblasts. Cyld(Delta 9/Delta 9) newborn mice were smaller than wild-type littermates with a short and kinky tail and no major developmental defects. However, Cyld(Delta 9/Delta 9) mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 Cyld(Delta 9/Delta 9) lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle and endothelial structures. Thus, it is thought that CYLD has an important role in lung maturation, which may underlie the development of many cases of lung cancer." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008175", "http://www.disease-ontology.org/api/metadata/DOID:1324" ], "type": "yesno", "id": "5545e926d355485447000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-\u03baB survival signaling in lung cancer cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22017589", "endSection": "title" }, { "offsetInBeginSection": 521, "offsetInEndSection": 834, "text": "increased expression of CYLD directly blocks TRAIL-induced NF-\u03baB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-\u03baB activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22017589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Truncation of the catalytic domain of the cylindromatosis tumor suppressor impairs lung maturation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "endSection": "title" }, { "offsetInBeginSection": 326, "offsetInEndSection": 462, "text": "down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 1584, "text": "Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. In accordance with previous studies, fibroblasts from Cyld(Delta 9/Delta 9) embryos had hyperactive nuclear factor kappaB and c-Jun kinase pathways compared with control fibroblasts. Cyld(Delta 9/Delta 9) newborn mice were smaller than wild-type littermates with a short and kinky tail and no major developmental defects. However, Cyld(Delta 9/Delta 9) mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 Cyld(Delta 9/Delta 9) lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle. and endothelial structures. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 463, "text": "Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1585, "text": "Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 462, "text": "Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "endSection": "abstract" } ] }, { "body": "Which medical diagnostic tests are used to test kidney function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23526674", "http://www.ncbi.nlm.nih.gov/pubmed/22797727", "http://www.ncbi.nlm.nih.gov/pubmed/2510609", "http://www.ncbi.nlm.nih.gov/pubmed/23097569", "http://www.ncbi.nlm.nih.gov/pubmed/20978142", "http://www.ncbi.nlm.nih.gov/pubmed/22257305", "http://www.ncbi.nlm.nih.gov/pubmed/23194995", "http://www.ncbi.nlm.nih.gov/pubmed/23952327", "http://www.ncbi.nlm.nih.gov/pubmed/23449218", "http://www.ncbi.nlm.nih.gov/pubmed/22973348", "http://www.ncbi.nlm.nih.gov/pubmed/23106053", "http://www.ncbi.nlm.nih.gov/pubmed/23650931", "http://www.ncbi.nlm.nih.gov/pubmed/23521456" ], "ideal_answer": [ "Most common tests used in diagnosing normal kidney function include blood tests such as serum creatinine levels, glomerular filtration rate (GFR) and blood urea nitrogen (BUN) levels, also medical imaging tests like ultrasound and CT Scan. Additionally kidney biopsy is used in more direct but invasive approach. Lastly, and probably the most relevant tests to kidney function are urine tests along the lines of urinalysis, urine protein levels and microalbuminuria creatinine clearance." ], "exact_answer": [ [ "Blood Tests" ], [ "Imaging Tests" ], [ "Kidney Biopsy" ], [ "Urine Tests" ], [ "estimated GFR (eGFR)" ], [ "Decreased tryptophan (TRP)" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4273958", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046449", "http://www.uniprot.org/uniprot/CRNA_PSEPU", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003093", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003105", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003104", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005919", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003404", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001806" ], "type": "list", "id": "5311b99ae3eabad021000004", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 196, "text": "kidney dysfunction and decreased glomerular filtration rate (GFR) are diagnosed by the evaluation of changes in the serum creatinine (SCr) and blood urea nitrogen (BUN) concentrations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23952327", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 646, "text": "Renal biomarkers, especially those present in urine, may be useful for the study of both acute and chronic nephropathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23952327", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 942, "text": "The International Renal Interest Society (IRIS) canine AKI grading system and the implementation of urinary biomarkers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23952327", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 181, "text": "Decreased tryptophan (TRP) and increased kynurenine (KYN) and kynurenic acid (KYNA) in blood have been reported in patients and experimental animals with renal diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23650931", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 922, "text": "Acute kidney injury was defined as a decrease in estimated glomerular filtration rate of 50% or more from the beginning of vancomycin therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526674", "endSection": "abstract" }, { "offsetInBeginSection": 1810, "offsetInEndSection": 1985, "text": " In critically ill children, the development of reversible AKI during vancomycin therapy is associated with administration of nephrotoxic drugs and an elevated BUN: Scr ratio.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526674", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 364, "text": "The physiologic determination of renal status is the measured glomerular filtration rate (mGFR). Serum creatinine, blood urea nitrogen, cystatin C, and estimated GFR (eGFR), based on serum creatinine have failed to replace mGFR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23521456", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1132, "text": "After kidney donation, renal function measured by blood urea nitrogen (BUN) and serum creatinine of all donors returned to normal within one week, and no serious complications were noticed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23106053", "endSection": "abstract" }, { "offsetInBeginSection": 1402, "offsetInEndSection": 1479, "text": " In living kidney donors GFR is not significantly correlated with age or sex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23106053", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 96, "text": "Increased proteinuria would lead to a larger risk for renal failure in the long term", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973348", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1705, "text": "A reduction of proteinuria in patients with non-diabetic renal disease was observed during the 4-month treatment with pioglitazone which continued for 2 months after the cessation of the treatment. However, 4 months after the cessation of the treatment, a little increase was detected in the level of proteinuria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973348", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1059, "text": "We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22797727", "endSection": "abstract" } ] }, { "body": "Against which protein is the antibody used for immonostaining of Lewy bodies raised?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11005264", "http://www.ncbi.nlm.nih.gov/pubmed/10867800", "http://www.ncbi.nlm.nih.gov/pubmed/15854770", "http://www.ncbi.nlm.nih.gov/pubmed/19272424", "http://www.ncbi.nlm.nih.gov/pubmed/22370907", "http://www.ncbi.nlm.nih.gov/pubmed/9600226", "http://www.ncbi.nlm.nih.gov/pubmed/12536227", "http://www.ncbi.nlm.nih.gov/pubmed/16691119", "http://www.ncbi.nlm.nih.gov/pubmed/10787032", "http://www.ncbi.nlm.nih.gov/pubmed/9759660", "http://www.ncbi.nlm.nih.gov/pubmed/10822429", "http://www.ncbi.nlm.nih.gov/pubmed/10967182", "http://www.ncbi.nlm.nih.gov/pubmed/11207422", "http://www.ncbi.nlm.nih.gov/pubmed/12722831" ], "ideal_answer": [ "alpha-Synuclein is a presynaptic protein, which was identified as a specific component of Lewy bodies (LB) and Lewy neurites. Therefore, immunostaining for detecting the presence of Lewy bodies is carried out using antibodies against alpha-synuclein." ], "exact_answer": [ "alpha-Synuclein" ], "concepts": [ "http://www.uniprot.org/uniprot/SYUA_SERCA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016631", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003823" ], "type": "factoid", "id": "53189656b166e2b80600001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "\u03b1-Synuclein is the major protein associated with Lewy body dementia, Parkinson's disease and multiple system atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370907", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 518, "text": "With the aim to develop antibodies showing high specificity and sensitivity for disease-associated \u03b1-synuclein, synthetic peptides containing different amino acid sequences were used for immunization of mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "Parkinson's disease and dementia with Lewy bodies are very frequent neurological disorders of the elderly. Mutations in the alpha-synuclein (alphaSYN) gene cause Parkinson's disease, often associated with dementia. Neuropathologically these diseases are characterized by the presence of Lewy bodies and Lewy neurites, intraneuronal inclusions mostly composed of alphaSYN protein fibrils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19272424", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 677, "text": "Immunohistochemistry for alpha-synuclein revealed LBs in 31 of 290 PSP cases (11%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16691119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "We immunohistochemically investigated the degeneration processes of the nigro-striatal and nigro-amygdaloid pathways and the relationship between the loss of dopaminergic neurons and Lewy bodies (LB) formation in the substantia nigra using 15 autopsied cases of dementia with Lewy bodies (DLB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15854770", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 650, "text": "The substantia nigra possessed alpha-synuclein-positive LB-bearing neurons that were almost evenly distributed, while the putamen exhibited diffuse or granular alpha-synuclein-immunostaining.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15854770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The major protein constituent of Lewy bodies (LBs), the pathological hallmark of Parkinson disease and dementia with Lewy bodies, is considered to be alpha-synuclein,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12722831", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 251, "text": "Recently, alpha-synuclein (alphaS) has been found to be a central constituent of LB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12536227", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 824, "text": "By having the antibody AFshp raised specifically to alpha-synuclein to label Parkinson disease-specific Lewy bodies and Lewy neurites as well as synaptic boutons containing the unaltered protein, an initial attempt is made to map the overall distribution pattern and describe the staining behavior of the immunoreactive punctae in select regions of the prosencephalon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11207422", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 880, "text": "Notably, carboxy-terminal alpha-syn epitopes were immunodominant in GCIs, but the entire panel of antibodies immunostained cortical Lewy bodies (LBs) in dementia with LBs brain with similar intensity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11005264", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1165, "text": "Discrete immunostaining was demonstrated in NFTs and neuropil threads with various antibodies against phosphorylated tau, and in LBs with antibody against alpha-synuclein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10967182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-synuclein as a component of Lewy bodies has heralded a new era in the study of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10867800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10822429", "endSection": "title" }, { "offsetInBeginSection": 358, "offsetInEndSection": 524, "text": "recent advances in immunostaining of alpha-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10822429", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1133, "text": "CLBs positive for alpha-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10822429", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1433, "text": "CLBs detected by alpha-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10822429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "alpha-Synuclein immunoreactivity in dementia with Lewy bodies", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10787032", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "alpha-Synuclein is a presynaptic protein recently identified as a specific component of Lewy bodies (LB) and Lewy neurites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10787032", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 738, "text": "alpha-Synuclein immunostaining was more specific than ubiquitin immunostaining in that it differentiated LB from globose tangles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10787032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP) (also known as alpha-synuclein) is a presynaptic terminal molecule that abnormally accumulates in the plaques of Alzheimer's disease (AD) and in the Lewy bodies (LBs) of Lewy body variant of AD, diffuse Lewy body disease, and Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9759660", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 725, "text": "To better understand the distribution of NACP/alpha-synuclein and its fragments in the LB-bearing neurons and neurites, as well as to clarify the patterns of NACP/alpha-synuclein compartmentalization, we studied NACP/alpha-synuclein immunoreactivity using antibodies against the C-terminal, N-terminal, and NAC regions after Proteinase K and formic acid treatment in the cortex of patients with LBs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9759660", "endSection": "abstract" }, { "offsetInBeginSection": 1656, "offsetInEndSection": 1872, "text": "Ultrastructural analysis revealed that NACP/alpha-synuclein immunoreactivity was diffusely distributed within the amorphous electrodense material in the LBs and as small clusters in the filaments of LBs and neurites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9759660", "endSection": "abstract" }, { "offsetInBeginSection": 1873, "offsetInEndSection": 2023, "text": "These results support the view that aggregated NACP/alpha-synuclein might play an important role in the pathogenesis of disorders associated with LBs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9759660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson's disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9600226", "endSection": "title" }, { "offsetInBeginSection": 341, "offsetInEndSection": 453, "text": "PD brain demonstrated alpha-synuclein immunoreactivity in nigral Lewy bodies, pale bodies and abnormal neurites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9600226", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 651, "text": "DLB cases demonstrated these findings as well as alpha-synuclein immunoreactivity in cortical Lewy bodies and CA2-3 neurites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9600226", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 833, "text": "These results suggest that, even in sporadic cases, there is an early and direct role for alpha-synuclein in the pathogenesis of PD and the neuropathologically related disorder DLB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9600226", "endSection": "abstract" } ] }, { "body": "Which are the main causes of fetal echogenic bowel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20932506", "http://www.ncbi.nlm.nih.gov/pubmed/22378220", "http://www.ncbi.nlm.nih.gov/pubmed/14626795", "http://www.ncbi.nlm.nih.gov/pubmed/9664617", "http://www.ncbi.nlm.nih.gov/pubmed/10364670", "http://www.ncbi.nlm.nih.gov/pubmed/22990134", "http://www.ncbi.nlm.nih.gov/pubmed/17364293", "http://www.ncbi.nlm.nih.gov/pubmed/18577682", "http://www.ncbi.nlm.nih.gov/pubmed/14663844", "http://www.ncbi.nlm.nih.gov/pubmed/7474061", "http://www.ncbi.nlm.nih.gov/pubmed/21606744", "http://www.ncbi.nlm.nih.gov/pubmed/11169342", "http://www.ncbi.nlm.nih.gov/pubmed/1415421", "http://www.ncbi.nlm.nih.gov/pubmed/10550877", "http://www.ncbi.nlm.nih.gov/pubmed/8633653", "http://www.ncbi.nlm.nih.gov/pubmed/10590441", "http://www.ncbi.nlm.nih.gov/pubmed/8142051", "http://www.ncbi.nlm.nih.gov/pubmed/8538346", "http://www.ncbi.nlm.nih.gov/pubmed/11717628", "http://www.ncbi.nlm.nih.gov/pubmed/10912967", "http://www.ncbi.nlm.nih.gov/pubmed/18254450", "http://www.ncbi.nlm.nih.gov/pubmed/20059439", "http://www.ncbi.nlm.nih.gov/pubmed/12835583", "http://www.ncbi.nlm.nih.gov/pubmed/19921962", "http://www.ncbi.nlm.nih.gov/pubmed/10419606", "http://www.ncbi.nlm.nih.gov/pubmed/18417974", "http://www.ncbi.nlm.nih.gov/pubmed/22589170" ], "ideal_answer": [ "Fetal echogenic bowel is mainly associated to feto-maternal, intramniotic bleeding but in several cases it is linked to cystic fibrosis, cytomegalovirus (CMV), herpes simplex virus and other viral infections and fetal aneuploidy.", "Fetal echogenic bowel (FEB) is a soft marker found on second trimester sonography. (PMID: 22990134) A disorder was diagnosed in 32.2% of the fetuses, cystic fibrosis being the most commonly identified (7.6%). We also found digestive malformations (7.0%), chromosomal abnormalities (3.7%), and maternofetal infections (3.7%). (PMID: 20932506) Brightly echogenic bowel in the second trimester was found to be associated with a significant risk of fetal aneuploidy. (PMID: 1415421) echogenic bowel does not uniformly herald an abnormal outcome. Echogenic bowel coexistent with other abnormalities (such as growth deficiency or structural malformations) may be a comarker for aneuploidy. (PMID: 8142051) 112 cases (57%) had a known etiology, which included chromosomal abnormality (7%), infection (4%), cystic fibrosis (1.5%), bowel abnormality (3%), bleeding or stained amniotic fluid (11%), Doppler abnormality (14%), malformation (16%) and miscellaneous (0.5%) (PMID: 12835583)" ], "exact_answer": [ [ "Itramniotic bleeding" ], [ "CMV infection" ], [ "Cystic Fibrosis (CF)" ], [ "Fetal aneuploidy" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058535", "http://www.disease-ontology.org/api/metadata/DOID:9779" ], "type": "list", "id": "5131fa145274a5fb07000009", "snippets": [ { "offsetInBeginSection": 1054, "offsetInEndSection": 1156, "text": "In group 2 and 3, two anomalies, anorectal malformation and cystic fibrosis, were detected postnatally", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990134", "endSection": "sections.0" }, { "offsetInBeginSection": 671, "offsetInEndSection": 774, "text": "Six had chromosomal/genetic abnormalities, two had congenital cytomegalovirus, none had cystic fibrosis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589170", "endSection": "sections.0" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1385, "text": "Primary bowel pathology is rare following the finding of FEB", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589170", "endSection": "sections.0" }, { "offsetInBeginSection": 899, "offsetInEndSection": 974, "text": "Maternal serology for cytomegalovirus (CMV) was performed in 49 (78%) cases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22378220", "endSection": "sections.0" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1181, "text": "Thirty-three pregnancies (53%) were tested for cystic fibrosis (CF) and 1 baby was confirmed to have CF postnatally", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22378220", "endSection": "sections.0" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1618, "text": "This study reiterates the increased prevalence of aneuploidy, CMV, CF and fetal growth restriction in pregnancies complicated by the midtrimester sonographic finding of FEB", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22378220", "endSection": "sections.0" }, { "offsetInBeginSection": 453, "offsetInEndSection": 616, "text": "Primary outcomes were IUGR, defined as birth weight less than the 10th percentile for gestational age and intrauterine fetal demise at 20 weeks or more of gestatio", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606744", "endSection": "sections.0" }, { "offsetInBeginSection": 780, "offsetInEndSection": 872, "text": "Analyses were repeated after excluding cases of aneuploidy, cytomegalovirus (CMV) infection,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606744", "endSection": "sections.0" }, { "offsetInBeginSection": 1969, "offsetInEndSection": 2114, "text": "The presence of echogenic bowel on ultrasonography is independently associated with an increased risk for both IUGR and intrauterine fetal demise", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606744", "endSection": "sections.0" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1133, "text": "This study highlights the importance of pregnancy ultrasound examinations and their efficiency in detecting cystic fibrosis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20932506", "endSection": "sections.0" }, { "offsetInBeginSection": 612, "offsetInEndSection": 836, "text": "A disorder was diagnosed in 32.2% of the fetuses, cystic fibrosis being the most commonly identified (7.6%). We also found digestive malformations (7.0%), chromosomal abnormalities (3.7%), and maternofetal infections (3.7%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20932506", "endSection": "sections.0" }, { "offsetInBeginSection": 781, "offsetInEndSection": 887, "text": "A potential association with placental abnormalities and a low prevalence of viral infections was observed", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20059439", "endSection": "sections.0" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1512, "text": "Our data suggests an inverse relationship between the maternal BMI and the detection of fetal EIF and/or EB", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19921962", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Fetal echogenic bowel at 17 weeks' gestational age as the early and only sign of a very long segment of Hirschsprung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18577682", "endSection": "title" }, { "offsetInBeginSection": 17, "offsetInEndSection": 103, "text": "fetal ultrasound findings associated with intrauterine cytomegalovirus (CMV) infection", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18417974", "endSection": "sections.0" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1235, "text": "the combination of hydrops fetalis, cerebral hemorrhage, and hyperechoic bowel should raise the possibility of a CMV infection", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18417974", "endSection": "sections.0" }, { "offsetInBeginSection": 706, "offsetInEndSection": 914, "text": "strongly associated with adverse pregnancy outcome due to utero-placental insufficiency, particularly in women with elevated maternal serum alpha-fetoprotein concentration due to severe feto-maternal bleeding", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18254450", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Congenital cytomegalovirus infection presenting with echogenic bowel and oligohydramnios.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17364293", "endSection": "title" }, { "offsetInBeginSection": 450, "offsetInEndSection": 515, "text": "Five cases of trisomy 21 and one case of trisomy 18 were detected", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1415421", "endSection": "sections.0" }, { "offsetInBeginSection": 809, "offsetInEndSection": 929, "text": "Brightly echogenic bowel in the second trimester was found to be associated with a significant risk of fetal aneuploidy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1415421", "endSection": "sections.0" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1126, "text": "echogenic bowel does not uniformly herald an abnormal outcome. Echogenic bowel coexistent with other abnormalities (such as growth deficiency or structural malformations) may be a comarker for aneuploidy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8142051", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Congenital cytomegalovirus infection with oligohydramnios and echogenic bowel at 14 weeks' gestation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7474061", "endSection": "title" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1220, "text": "Parental CF carrier testing and amniocentesis to identify aneuploidy or fetal CF status has a high positive ascertainment rate in fetuses with echogenic bowel grades 2 and 3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8538346", "endSection": "sections.0" }, { "offsetInBeginSection": 1804, "offsetInEndSection": 1968, "text": "Swallowing of amniotic fluid after intraamniotic bleeding seems implicated in the etiology of second-trimester echogenic bowel in both euploid and aneuploid fetuses", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8633653", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Fetal echogenic bowel and a dilated loop of bowel associated with cystic fibrosis (CF) mutations delta F508 and 2183AA-->G", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9664617", "endSection": "title" }, { "offsetInBeginSection": 319, "offsetInEndSection": 385, "text": "Fifteen cases (19%) were associated with maternal vaginal bleeding", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10364670", "endSection": "sections.0" }, { "offsetInBeginSection": 613, "offsetInEndSection": 722, "text": "Five fetuses (6.3%) had evidence of bowel obstruction or perforation not associated with cystic fibrosis (CF)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10364670", "endSection": "sections.0" }, { "offsetInBeginSection": 724, "offsetInEndSection": 926, "text": "Chromosomal aberrations were found in 5 fetuses (6.3%). Intrauterine infection with cytomegalovirus, herpes simplex virus, varicella-zoster virus, or parvovirus B-19 was documented in 5 patients (6.3%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10364670", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Fetal echogenic bowel has been reported as a normal variant in the second trimester, and has also been associated with an adverse fetal outcome, including cystic fibrosis (CF)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10419606", "endSection": "sections.0" }, { "offsetInBeginSection": 918, "offsetInEndSection": 969, "text": "Intra-amniotic bleeding can lead to echogenic bowel", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10912967", "endSection": "sections.0" }, { "offsetInBeginSection": 549, "offsetInEndSection": 808, "text": "112 cases (57%) had a known etiology, which included chromosomal abnormality (7%), infection (4%), cystic fibrosis (1.5%), bowel abnormality (3%), bleeding or stained amniotic fluid (11%), Doppler abnormality (14%), malformation (16%) and miscellaneous (0.5%)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12835583", "endSection": "sections.0" } ] }, { "body": "How does trimetazidine affect intracellular kinase signaling in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20167841", "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "http://www.ncbi.nlm.nih.gov/pubmed/19546072", "http://www.ncbi.nlm.nih.gov/pubmed/15616764" ], "ideal_answer": [ "Trimetazidine activates AMPK in diabetic myocardium. Trimetazidine when administered before reperfusion results in activation of p38 mitogen-activated protein kinase and Akt signaling. Trimetazidine when administered during reperfusion does not affect p38MAPK and JNK activation." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004706", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048670", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004709", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004708", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020930", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008349", "http://www.uniprot.org/uniprot/M4K1_HUMAN", "http://www.uniprot.org/uniprot/M4K3_MOUSE", "http://www.uniprot.org/uniprot/M4K4_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014292", "http://www.biosemantics.org/jochem#4250101", "http://www.uniprot.org/uniprot/M3K1_ARATH", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000185", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048730", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000186", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048369", "http://www.biosemantics.org/jochem#4059120", "http://www.uniprot.org/uniprot/M4K5_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000165", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043408", "http://www.uniprot.org/uniprot/M4K2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048490", "http://www.uniprot.org/uniprot/ALPK2_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031435", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048768", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048669", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048748", "http://www.uniprot.org/uniprot/M4K2_HUMAN", "http://www.uniprot.org/uniprot/ALPK2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010627", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0007243", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020929", "http://www.uniprot.org/uniprot/M4K3_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048688", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042655", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042656", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000197", "http://www.uniprot.org/uniprot/M4K1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0051390", "http://www.uniprot.org/uniprot/M4K5_MOUSE", "http://www.uniprot.org/uniprot/M4K3_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048370", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048728", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008545", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0033161", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048848" ], "type": "summary", "id": "5171393e8ed59a060a000005", "snippets": [ { "offsetInBeginSection": 1121, "offsetInEndSection": 1377, "text": "The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1 alpha were involved in this process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "endSection": "sections.0" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1751, "text": "the results demonstrated that TMZ is cardioprotective when administered before reperfusion and that this protection appears to be mediated by activation of p38 mitogen-activated protein kinase and Akt signaling. The study emphasizes the importance of administering TMZ before reflow to prevent reperfusion-mediated cardiac injury and dysfunction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20167841", "endSection": "sections.0" }, { "offsetInBeginSection": 874, "offsetInEndSection": 937, "text": "TMZ induced cardioprotection did not involve p38 MAPK and JNKs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15616764", "endSection": "sections.0" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1017, "text": "Phospho-p38 MAPK and JNKs levels after I/R were not changed with TMZ treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15616764", "endSection": "sections.0" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1107, "text": "Trimetazidine also caused AMPK activation and reduced PGC-1 alpha expression in the hearts of db/db mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "endSection": "sections.0" } ] }, { "body": "Which is the enzymatic activity of the myotubularin family of proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15998640", "http://www.ncbi.nlm.nih.gov/pubmed/23086420", "http://www.ncbi.nlm.nih.gov/pubmed/12646134", "http://www.ncbi.nlm.nih.gov/pubmed/21372139", "http://www.ncbi.nlm.nih.gov/pubmed/22578719", "http://www.ncbi.nlm.nih.gov/pubmed/17346927", "http://www.ncbi.nlm.nih.gov/pubmed/12788949", "http://www.ncbi.nlm.nih.gov/pubmed/20188094", "http://www.ncbi.nlm.nih.gov/pubmed/23818870", "http://www.ncbi.nlm.nih.gov/pubmed/12118066", "http://www.ncbi.nlm.nih.gov/pubmed/11846405", "http://www.ncbi.nlm.nih.gov/pubmed/11275328", "http://www.ncbi.nlm.nih.gov/pubmed/21510942", "http://www.ncbi.nlm.nih.gov/pubmed/23114011", "http://www.ncbi.nlm.nih.gov/pubmed/12925573", "http://www.ncbi.nlm.nih.gov/pubmed/14690594", "http://www.ncbi.nlm.nih.gov/pubmed/23857703", "http://www.ncbi.nlm.nih.gov/pubmed/19325702", "http://www.ncbi.nlm.nih.gov/pubmed/21175430", "http://www.ncbi.nlm.nih.gov/pubmed/12018406", "http://www.ncbi.nlm.nih.gov/pubmed/12045210", "http://www.ncbi.nlm.nih.gov/pubmed/16828287", "http://www.ncbi.nlm.nih.gov/pubmed/20736309", "http://www.ncbi.nlm.nih.gov/pubmed/12554688", "http://www.ncbi.nlm.nih.gov/pubmed/16410353", "http://www.ncbi.nlm.nih.gov/pubmed/11733541", "http://www.ncbi.nlm.nih.gov/pubmed/22647598", "http://www.ncbi.nlm.nih.gov/pubmed/16289848", "http://www.ncbi.nlm.nih.gov/pubmed/16262718", "http://www.ncbi.nlm.nih.gov/pubmed/12829232", "http://www.ncbi.nlm.nih.gov/pubmed/16914545", "http://www.ncbi.nlm.nih.gov/pubmed/16787938" ], "ideal_answer": [ "The myotubularin family of proteins are lipid inositol phosphatases" ], "exact_answer": [ "lipid inositol phosphatase activity" ], "type": "factoid", "id": "54d6562c3706e8952800000b", "snippets": [ { "offsetInBeginSection": 518, "offsetInEndSection": 554, "text": "myotubularin family of phosphatases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23857703", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 282, "text": "Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., \"MTMRs\")", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818870", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 463, "text": "myotubalarin family phosphatase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23114011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "MTMR2 is a member of the myotubularin family of inositol lipid phosphatases, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21372139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Myotubularin related protein 2 (MTMR2) is a member of the myotubularin family of phosphoinositide lipid phosphatases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21510942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Myotubularin phosphoinositide phosphatases: cellular functions and disease pathophysiology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22578719", "endSection": "title" }, { "offsetInBeginSection": 481, "offsetInEndSection": 795, "text": "Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11275328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Myotubularin is the archetype of a family of highly conserved protein-tyrosine phosphatase-like enzymes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11733541", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 364, "text": "we and others have characterized myotubularin as a potent and specific phosphatidylinositol 3-phosphate 3-phosphatase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11846405", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 544, "text": "MTMR2 encodes a member of the myotubularin family of phosphoinositide-3-phosphatases, which dephosphorylate phosphatidylinositol 3-phosphate (PI(3)P) and bisphosphate PI(3,5)P2. MTMR13 encodes a large, uncharacterized member of the myotubularin family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15998640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Myotubularin-related proteins are a large subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14690594", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 409, "text": "Myotubularin, the gene mutated in myotubular myopathy, functions as a lipid phosphatase with specificity for PtdIns(3)P.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12018406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "The myotubularin family: novel phosphoinositide regulators.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12018406", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "The myotubularins are a large family of inositol polyphosphate 3-phosphatases that", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647598", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 422, "text": "The myotubularin family consists of 16 different proteins, 9 members of which possess catalytic activity, dephosphorylating phosphatidylinositol 3-phosphate [PtdIns(3)P] and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)] at the D-3 position.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647598", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Myotubularin phosphoinositide phosphatases in human diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The MTM (myotubularin)/MTMR (myotubularin-related) protein family is comprised of 15 lipid phosphatases, of which nine members are catalytically active. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "The myotubularin family of lipid phosphatases ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175430", "endSection": "title" } ] }, { "body": "Can we detect DNA strand asymmetries using dinucleotide relative abundance \"genomic signatures\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15046306", "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "http://www.ncbi.nlm.nih.gov/pubmed/9294192", "http://www.ncbi.nlm.nih.gov/pubmed/18799480", "http://www.ncbi.nlm.nih.gov/pubmed/9520433", "http://www.ncbi.nlm.nih.gov/pubmed/10430918", "http://www.ncbi.nlm.nih.gov/pubmed/9190805", "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "http://www.ncbi.nlm.nih.gov/pubmed/10066522" ], "ideal_answer": [ "The set of dinucleotide relative abundances can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome. Thus, dinucleotide relative abundance profiles are species-type specific. These profiles are computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). Dinucleotide relative abundance \"genomic signatures\" are strand-independent second-order DNA features. Thus, they cannot be used to detect DNA strand asymmetries." ], "exact_answer": "no", "type": "yesno", "id": "55435aeced966d112c000007", "snippets": [ { "offsetInBeginSection": 523, "offsetInEndSection": 702, "text": "comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18799480", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 477, "text": "the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 116, "text": "dinucleotide relative abundance values (the genomic signature)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15046306", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 212, "text": "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 532, "text": "The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 369, "text": "The genome signatures (dinucleotide relative abundance values)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10430918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Early biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10066522", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 643, "text": "the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10066522", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 773, "text": "the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Dinucleotide relative abundance extremes: a genomic signature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 476, "text": "Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 488, "text": "Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9294192", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 887, "text": "Dinucleotide relative abundances (i.e., dinucleotide representations normalized by the component nucleotide frequencies) are consonant with respect to the leading and lagging strands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9520433", "endSection": "abstract" } ] }, { "body": "What is the percentage of responders to tetrabenazine treatment for dystonia in children?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19808991", "http://www.ncbi.nlm.nih.gov/pubmed/9040721", "http://www.ncbi.nlm.nih.gov/pubmed/12710012", "http://www.ncbi.nlm.nih.gov/pubmed/6128697", "http://www.ncbi.nlm.nih.gov/pubmed/3400500", "http://www.ncbi.nlm.nih.gov/pubmed/6502174", "http://www.ncbi.nlm.nih.gov/pubmed/9549503", "http://www.ncbi.nlm.nih.gov/pubmed/18555882", "http://www.ncbi.nlm.nih.gov/pubmed/2904118", "http://www.ncbi.nlm.nih.gov/pubmed/6889706", "http://www.ncbi.nlm.nih.gov/pubmed/22515742" ], "ideal_answer": [ "Tetrabenazine is used empirically in the treatment of dystonia in children with variable success. Observational studies report improvement of up to > 60% of the patients." ], "exact_answer": [ "up to > 60%" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:543", "http://www.disease-ontology.org/api/metadata/DOID:5159", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014103", "http://www.disease-ontology.org/api/metadata/DOID:544", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013747", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004421", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020821", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009069" ], "type": "factoid", "id": "515ddda6298dcd4e5100001f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 94, "text": "report a patient with dystonia secondary to bilateral lesions of the basal ganglia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808991", "endSection": "sections.0" }, { "offsetInBeginSection": 494, "offsetInEndSection": 635, "text": "The patient's dystonia responded to Trihexyphenidyl and to tetrabenazine, but these medications needed to be stopped because of side effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808991", "endSection": "sections.0" }, { "offsetInBeginSection": 239, "offsetInEndSection": 375, "text": "An 8-year-old girl received 53 grays radiotherapy after surgery for craniopharyngioma. One year later she developed generalized dystonia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18555882", "endSection": "sections.0" }, { "offsetInBeginSection": 481, "offsetInEndSection": 606, "text": "Pharmacological treatment with tetrabenazine, clonazepam and trihexiphenydile allowed a very limited improvement of dystonia;", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18555882", "endSection": "sections.0" }, { "offsetInBeginSection": 167, "offsetInEndSection": 249, "text": "welve cases of status dystonicus, of various underlying aetiologies, are presented", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9549503", "endSection": "sections.0" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1237, "text": "Drug therapy with benzhexol, tetrabenazine and pimozide or haloperidol may be beneficial in some cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9549503", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Over the past 15 years we have treated 526 patients with severe hyperkinetic movement disorders with tetrabenazine (TBZ)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9040721", "endSection": "sections.0" }, { "offsetInBeginSection": 502, "offsetInEndSection": 799, "text": "The global response rating of 1 (marked improvement) was recorded in 89.2% of 93 patients with tardive stereotypy, 83.3% of 12 with myoclonus, 82.8% of 29 with Huntington's disease, 80.5% of 82 with tardive dystonia, 79.3% of 29 with other movement disorders, 62.9% of 108 with idiopathic dystonia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9040721", "endSection": "sections.0" }, { "offsetInBeginSection": 462, "offsetInEndSection": 692, "text": "Twelve adults with severe axial dystonia, and two children with life-threatening generalised dystonia were treated with a combination of a low constant dose of tetrabenazine to which were added pimozide and benzhexol as necessary.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6502174", "endSection": "sections.0" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1582, "text": "When benzhexol treatment alone fails in adults with severe disabling axial dystonia, or in children with life-threatening generalised dystonia, combined therapy with tetrabenazine, pimozide and benzhexol may give valuable symptomatic relief.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6502174", "endSection": "sections.0" }, { "offsetInBeginSection": 330, "offsetInEndSection": 424, "text": "We present 42 patients with tardive dystonia. The age of onset of dystonia was 13 to 60 years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6128697", "endSection": "sections.0" }, { "offsetInBeginSection": 682, "offsetInEndSection": 804, "text": "The most frequently helpful medications were tetrabenazine (68% of patients improved) and anticholinergics (39% improved).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6128697", "endSection": "sections.0" }, { "offsetInBeginSection": 151, "offsetInEndSection": 373, "text": "8-year-old boy of non-Jewish, Mexican-American descent with autosomal-dominant dystonia musculorum deformans who developed rapidly progressive and severe generalized dystonia, hyperpyrexia, myoglobinuria, and renal failure", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6889706", "endSection": "sections.0" }, { "offsetInBeginSection": 402, "offsetInEndSection": 468, "text": "Transient improvement was achieved with tetrabenazine and baclofen", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6889706", "endSection": "sections.0" } ] }, { "body": "Is there any relationship between histone ubiquitylation and splicing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23824326", "http://www.ncbi.nlm.nih.gov/pubmed/19561118", "http://www.ncbi.nlm.nih.gov/pubmed/23209445", "http://www.ncbi.nlm.nih.gov/pubmed/22188810" ], "ideal_answer": [ "Yes, in the case of histone H2B" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054875", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025801", "http://www.uniprot.org/uniprot/UBIQ_CAMDR", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008380", "http://www.biosemantics.org/jochem#4278518", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016574" ], "type": "yesno", "id": "5344194daeec6fbd07000006", "snippets": [ { "offsetInBeginSection": 387, "offsetInEndSection": 551, "text": "histone H2B-specific deubiquitinase and demonstrate that H2B deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23824326", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 357, "text": "H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22188810", "endSection": "abstract" }, { "offsetInBeginSection": 35, "offsetInEndSection": 78, "text": "H2B ubiquitination by facilitating splicing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561118", "endSection": "title" }, { "offsetInBeginSection": 1505, "offsetInEndSection": 1574, "text": "pre-mRNA splicing plays a critical role in histone H2B ubiquitination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561118", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1540, "text": "unanticipated functional link between histone H2B ubiquitination and pre-mRNA splicing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23209445", "endSection": "abstract" } ] }, { "body": "Which disease can be treated with Delamanid?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25404020", "http://www.ncbi.nlm.nih.gov/pubmed/26288734", "http://www.ncbi.nlm.nih.gov/pubmed/25327169", "http://www.ncbi.nlm.nih.gov/pubmed/24729727", "http://www.ncbi.nlm.nih.gov/pubmed/22670901" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A20909765", "o": "C516022" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "D004194" } ], "ideal_answer": [ "Delamanid is used in patients with multidrug-resistant tuberculosis." ], "exact_answer": [ "tuberculosis" ], "type": "factoid", "id": "56bc7d71ac7ad10019000018", "snippets": [ { "offsetInBeginSection": 189, "offsetInEndSection": 362, "text": "Recently approved anti-Tb drugs (bedaquiline and delamanid) have the potential to induce arrhythmia and are recommended in patients with MDR-Tb when other alternatives fail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26288734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Delamanid: a review of its use in patients with multidrug-resistant tuberculosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404020", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Delamanid (Deltyba(\u00ae)), a nitroimidazo-oxazole derivative, is a new anti-tuberculosis (TB) drug which exhibits potent in vitro and in vivo antitubercular activity against drug-susceptible and -resistant strains of Mycobacterium tuberculosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404020", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 758, "text": "In a robust phase\u00a0II trial in adult patients with MDR-TB, oral delamanid 100\u00a0mg twice daily for 2\u00a0months plus an optimized background regimen improved sputum culture conversion rates to a significantly greater extent than placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404020", "endSection": "abstract" }, { "offsetInBeginSection": 1653, "offsetInEndSection": 1769, "text": "In conclusion, delamanid is a useful addition to the treatment options currently available for patients with MDR-TB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Delamanid when other anti-tuberculosis-treatment regimens failed due to resistance or tolerability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25327169", "endSection": "title" }, { "offsetInBeginSection": 272, "offsetInEndSection": 533, "text": "This review covers the efficacy and safety of delamanid for MDR-TB.AREA COVERED: This paper reviews the pharmacological profile of delamanid and the results of clinical trials evaluating its efficacy for treating MDR-TB in combination with other anti-TB drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25327169", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 750, "text": "EXPERT OPINION: Delamanid showed potent activity against drug-susceptible and -resistant Mycobacterium tuberculosis in both in vitro and in vivo studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25327169", "endSection": "abstract" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1097, "text": "In addition, decreased mortality was observed in MDR-TB patients who received>6 months of delamanid treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25327169", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1455, "text": "Therefore, delamanid could be used as part of an appropriate combination regimen for pulmonary MDR-TB in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25327169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Delamanid for multidrug-resistant pulmonary tuberculosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22670901", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 741, "text": "BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis.METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22670901", "endSection": "abstract" }, { "offsetInBeginSection": 2099, "offsetInEndSection": 2206, "text": "This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22670901", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1484, "text": "Delamanid was not associated with clinically relevant drug-drug interactions, including with antiretroviral drugs and those commonly used in treating TB. Delamanid was generally well tolerated in patients with MDR-TB, with gastrointestinal adverse events and insomnia reported most commonly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404020", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1444, "text": "Linezolid may represent a valuable drug to treat cases of XDR-TB. Delamanid, bedaquiline, and PA-824 are new anti-TB agents in the development pipeline that have the potential to enhance the cure rate of XDR-TB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24729727", "endSection": "abstract" } ] }, { "body": "What was the aim of the COSS (Carotid Occlusion Surgery Study) clinical trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21772967", "http://www.ncbi.nlm.nih.gov/pubmed/22682265", "http://www.ncbi.nlm.nih.gov/pubmed/23101451", "http://www.ncbi.nlm.nih.gov/pubmed/22244016", "http://www.ncbi.nlm.nih.gov/pubmed/22645702", "http://www.ncbi.nlm.nih.gov/pubmed/22220280", "http://www.ncbi.nlm.nih.gov/pubmed/22068990", "http://www.ncbi.nlm.nih.gov/pubmed/21960571", "http://www.ncbi.nlm.nih.gov/pubmed/23909253", "http://www.ncbi.nlm.nih.gov/pubmed/24339571" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/trials/NCT00029146", "o": "\n The overall purpose of this research is to determine if a surgical operation called\n \"Extracranial-Intracranial Bypass\" can reduce the chance of a subsequent stroke in someone\n who has complete blockage in one main artery in the neck (the carotid artery) that supplies\n blood to the brain and has already suffered a small stroke. This surgery involves taking an\n artery from the scalp outside the skull, making a small hole in the skull and then connecting\n the scalp artery to a brain artery inside the skull. In this way the blockage of the carotid\n artery in the neck is bypassed and more blood can flow to the brain. In some people natural\n bypass arteries develop and the brain is already getting plenty of blood. These people have a\n low risk of stroke if they take medicine. In other people, no natural bypass arteries develop\n so less blood flows to their brains. This second group has a much higher risk of stroke while\n taking medicine, as high as 25-50% within the next two years. It is this second group of\n people who may benefit from having the bypass operation and who are the candidates for this\n study.\n\n This bypass surgery is considered experimental because it is not generally performed for this\n condition and it is unknown whether it leads to a decrease, an increase or no change in the\n risk of stroke. In order to determine if people fit into this second group of people who may\n benefit from the bypass operation they need to have a test called a PET scan. The PET scan\n measures the amount of blood that is getting to the brain and the amount of oxygen that the\n brain is using. The PET scan uses radioactive oxygen and water and is experimental (not\n approved by the United States Food and Drug Administration). If the PET scan shows that less\n blood is getting to the brain, there will be a 50-50 chance (like a coin toss) of receiving\n the bypass surgery or not. There will then be follow-up visits to the clinic one month later\n and then every three months for two years to check on the appropriate medical treatment that\n everyone will receive and to determine who has had a stroke.\n\n The study hypothesis is that extracranial-intracranial bypass surgery when added to best\n medical therapy can reduce by 40 percent subsequent stroke within two years in participants\n with recent TIA ('ministroke\") or stroke (32 kg/m(2)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21631446", "endSection": "sections.0" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1159, "text": "A prospective comparative study including 63 patients with PCOS has been done during 2 years. Women were randomly allocated to clomifene + Metformin (Metformin group, Metformin took during 8 weeks, 850 mg twice a day, plus Clomifene 100 mg per day during five days) or Clomifene only (100 mg per day during five days)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20517830", "endSection": "sections.0" }, { "offsetInBeginSection": 1854, "offsetInEndSection": 2033, "text": "Our conclusion is that Metformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement, excluding ART cycles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20517830", "endSection": "sections.0" }, { "offsetInBeginSection": 442, "offsetInEndSection": 628, "text": "A prospective, randomized, double-blind 26 week long study was undertaken in 50 women with PCOS. They all received diet and lifestyle counselling, and metformin 850 mg three times daily.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19342396", "endSection": "sections.0" }, { "offsetInBeginSection": 155, "offsetInEndSection": 275, "text": "nti-M\u00fcllerian hormone (AMH) levels reflect the number of small antral follicles in the ovaries and are elevated in PCOS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19342396", "endSection": "sections.0" }, { "offsetInBeginSection": 1602, "offsetInEndSection": 1736, "text": "Six months of androgen suppression by either metformin or low-dose dexamethasone treatment failed to influence circulating AMH levels.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19342396", "endSection": "sections.0" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1139, "text": "The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802325", "endSection": "sections.0" }, { "offsetInBeginSection": 1735, "offsetInEndSection": 1854, "text": "Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802325", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15117902", "endSection": "title" }, { "offsetInBeginSection": 27, "offsetInEndSection": 159, "text": "investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome (PCOS) scheduled for IVF stimulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15117902", "endSection": "sections.0" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1753, "text": "Pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome. However, among normal weight PCOS women, pre-treatment with metformin tends to improve pregnancy rates.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15117902", "endSection": "sections.0" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1218, "text": "Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12364442", "endSection": "sections.0" }, { "offsetInBeginSection": 407, "offsetInEndSection": 493, "text": "double-blind, placebo-controlled approach with detailed assessment of ovarian activity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11836287", "endSection": "sections.0" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 2185, "text": "The effect of metformin on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the metformin group. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the metformin group, whereas the placebo group actually increased weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the metformin-treated group. Metabolic risk factor benefits of metformin treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11836287", "endSection": "sections.0" }, { "offsetInBeginSection": 2262, "offsetInEndSection": 2669, "text": "We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11836287", "endSection": "sections.0" }, { "offsetInBeginSection": 193, "offsetInEndSection": 304, "text": "studies evaluating metformin treatment in women with clomiphene citrate (CC)-resistant polycystic ovaries (PCO)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11473953", "endSection": "sections.0" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1273, "text": "There was no improvement in the ovulation rate despite a significant reduction of body mass index, serum testosterone and fasting leptin concentrations in the metformin group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11473953", "endSection": "sections.0" } ] }, { "body": "List the main proteases used for sample digestion in proteomics.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23728546", "http://www.ncbi.nlm.nih.gov/pubmed/24140975", "http://www.ncbi.nlm.nih.gov/pubmed/23606249", "http://www.ncbi.nlm.nih.gov/pubmed/24106208", "http://www.ncbi.nlm.nih.gov/pubmed/24012793", "http://www.ncbi.nlm.nih.gov/pubmed/24136523", "http://www.ncbi.nlm.nih.gov/pubmed/23576383", "http://www.ncbi.nlm.nih.gov/pubmed/24168082", "http://www.ncbi.nlm.nih.gov/pubmed/23710360", "http://www.ncbi.nlm.nih.gov/pubmed/23703833", "http://www.ncbi.nlm.nih.gov/pubmed/22324799", "http://www.ncbi.nlm.nih.gov/pubmed/23792921", "http://www.ncbi.nlm.nih.gov/pubmed/24133050", "http://www.ncbi.nlm.nih.gov/pubmed/23580477", "http://www.ncbi.nlm.nih.gov/pubmed/23454304", "http://www.ncbi.nlm.nih.gov/pubmed/24144163", "http://www.ncbi.nlm.nih.gov/pubmed/23943586", "http://www.ncbi.nlm.nih.gov/pubmed/23775586", "http://www.ncbi.nlm.nih.gov/pubmed/20218731", "http://www.ncbi.nlm.nih.gov/pubmed/23819575", "http://www.ncbi.nlm.nih.gov/pubmed/24116745" ], "ideal_answer": [ "Trypsin is the main protease used in proteomics followed by Asp-N, chymotrypsin, LysC, GluC and thermolysin." ], "exact_answer": [ [ "trypsin" ], [ "Asp-N" ], [ "chymotrypsin" ], [ "LysC" ], [ "Glu-C" ], [ "thermolysin" ] ], "type": "list", "id": "5505eed08e1671127b000006", "snippets": [ { "offsetInBeginSection": 1144, "offsetInEndSection": 1199, "text": "the consecutive use of endoproteinases LysC and trypsin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22324799", "endSection": "abstract" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1226, "text": " Asp-N to trypsin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20218731", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 467, "text": " tryptic digestion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24168082", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1363, "text": "tryptic digest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24144163", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 175, "text": "enzymatic digestion is most commonly performed using trypsin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24144163", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 40, "text": "chymotrypsin/trypsin digestion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136523", "endSection": "title" }, { "offsetInBeginSection": 550, "offsetInEndSection": 744, "text": "In this method, chymotrypsin, single or in combination with trypsin, was used, which enabled to obtain proteolytic peptides from the hydrophobic regions and to identify new oil bodies' proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136523", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 124, "text": "proteins were digested by thermolysin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140975", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 30, "text": "tryptic digestion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24133050", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 123, "text": "protein digestion by trypsin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24133050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Trypsin is an endoprotease commonly used for sample preparation in proteomics experiments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24116745", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 72, "text": "tryptic digestion ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106208", "endSection": "title" }, { "offsetInBeginSection": 176, "offsetInEndSection": 200, "text": "direct tryptic digestion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24012793", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 295, "text": " trypsin digestion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23943586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Tryptic digestion is an important component of most proteomics experiments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23819575", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 753, "text": "We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23792921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Getting intimate with trypsin, the leading protease in proteomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23775586", "endSection": "title" }, { "offsetInBeginSection": 593, "offsetInEndSection": 633, "text": "sample preparation via trypsin digestion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728546", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 664, "text": " in-gel digested with trypsin, chymotrypsin, Asp-N, or trypsin plus Asp-N in triplicate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23710360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "In this study, we examined the use of multiple proteases (trypsin, LysC, tandem LysC/trypsin) on both protein identification and quantification ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23703833", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 503, "text": "digested with LysC and trypsin, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23606249", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 720, "text": "In-gel trypsin digestion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Magnetic bead cellulose activated with divinyl sulfone was used for the immobilization of Staphylococcus aureus endoproteinase Glu-C (EC 3.4.21.19).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576383", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 820, "text": "protease digestion with AspN or trypsin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23454304", "endSection": "abstract" } ] }, { "body": "Which proteins act as factors that promote transcription-coupled repair in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18707026", "http://www.ncbi.nlm.nih.gov/pubmed/24554077", "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "http://www.ncbi.nlm.nih.gov/pubmed/15687384", "http://www.ncbi.nlm.nih.gov/pubmed/20110508", "http://www.ncbi.nlm.nih.gov/pubmed/20702425", "http://www.ncbi.nlm.nih.gov/pubmed/21559463", "http://www.ncbi.nlm.nih.gov/pubmed/17572090", "http://www.ncbi.nlm.nih.gov/pubmed/8807287", "http://www.ncbi.nlm.nih.gov/pubmed/9535092", "http://www.ncbi.nlm.nih.gov/pubmed/21145481", "http://www.ncbi.nlm.nih.gov/pubmed/24118570", "http://www.ncbi.nlm.nih.gov/pubmed/20696893", "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "http://www.ncbi.nlm.nih.gov/pubmed/20638914", "http://www.ncbi.nlm.nih.gov/pubmed/12086674", "http://www.ncbi.nlm.nih.gov/pubmed/16469698", "http://www.ncbi.nlm.nih.gov/pubmed/7869378", "http://www.ncbi.nlm.nih.gov/pubmed/20178806", "http://www.ncbi.nlm.nih.gov/pubmed/20436399", "http://www.ncbi.nlm.nih.gov/pubmed/22960746" ], "ideal_answer": [ "Transcription coupled nucleotide excision repair (TC-NER or TCR) is a cellular process by which UV-induced damage and other road-blocks encountered in the transcribed strand are restored. Bacterial transcription-coupled repair is initiated when RNA polymerase stalled at a DNA lesion is removed by Mfd (Mutation frequency decline), an ATP-dependent DNA translocase. Mfd is the major transcription repair coupling factor in bacteria. Also, the transcription elongation factor NusA, in addition to its role in recruiting translesion synthesis (TLS) DNA polymerases to gaps encountered during transcription, promotes an alternative class of TCR involved in the identification and removal of a class of lesion, such as the N(2)-f-dG lesion." ], "exact_answer": [ [ "Mfd" ], [ "NusA" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090262", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006283" ], "type": "list", "id": "55451e53bf90a13052000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 534, "text": "Transcription-coupled repair (TCR) is a cellular process by which some forms of DNA damage are repaired more rapidly from transcribed strands of active genes than from nontranscribed strands or the overall genome. In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Transcription coupled nucleotide excision repair (TC-NER) is involved in correcting UV-induced damage and other road-blocks encountered in the transcribed strand. Mutation frequency decline (Mfd) is a transcription repair coupling factor, involved in repair of template strand during transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21559463", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 622, "text": "the transcription-repair coupling factor, Mfd, promotes direct restart of the fork following the collision by facilitating displacement of the RNAP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "We report observations suggesting that the transcription elongation factor NusA promotes a previously unrecognized class of transcription-coupled repair (TCR) in addition to its previously proposed role in recruiting translesion synthesis (TLS) DNA polymerases to gaps encountered during transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20696893", "endSection": "abstract" }, { "offsetInBeginSection": 1382, "offsetInEndSection": 1524, "text": "NusA participates in an alternative class of TCR involved in the identification and removal of a class of lesion, such as the N(2)-f-dG lesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20696893", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 370, "text": "Bacterial transcription-coupled repair is initiated when RNA polymerase stalled at a DNA lesion is removed by Mfd, an ATP-dependent DNA translocase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Transcription-coupled repair, the targeted repair of the transcribed strands of active genes, is defective in bacteria, yeast, and human cells carrying mutations in mfd, RAD26 and ERCC6, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8807287", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 984, "text": "The effect of the bacterial transcription-repair coupling factor, Mfd, at such lesions is not known: it has been suggested that Mfd may promote mutagenesis by increasing the efficiency with which RNA polymerase bypasses non-bulky lesions, but it has also been reported that 8-oxoguanine, a major product of oxidative DNA damage that is efficiently bypassed by RNA polymerase, is subject to Mfd-dependent transcription-coupled repair in Escherichia coli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18707026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The transcription-repair coupling factor (TRCF, the product of the mfd gene) is a widely conserved bacterial protein that mediates transcription-coupled DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702425", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 679, "text": "Recent structural studies of the bacterial transcription-repair coupling factor, Mfd, have revealed a modular architecture in which an ATP-dependent DNA-based motor is coupled to protein-protein interaction domains that can attach the motor to RNA polymerase and the DNA repair protein UvrA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17572090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The bacterial Mfd protein is a transcription-repair coupling factor that performs two key functions during transcription-coupled DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687384", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 883, "text": "Mfd remains bound to the DNA in a long-lived complex that could act as a marker for sites of DNA damage, directing assembly of subsequent DNA repair factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Transcription and DNA repair are coupled in E. coli by the Mfd protein, which dissociates transcription elongation complexes blocked at nonpairing lesions and mediates recruitment of DNA repair proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086674", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 328, "text": "The first is to remove RNA polymerase (RNAP) complexes that have been stalled by a DNA lesion from the site of damage, and the second is to mediate the recruitment of DNA repair proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Coupling of transcription and DNA repair in bacteria is mediated by transcription-repair coupling factor (TRCF, the product of the mfd gene), which removes transcription elongation complexes stalled at DNA lesions and recruits the nucleotide excision repair machinery to the site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16469698", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 882, "text": "Mfd remains bound to the DNA in a long-lived complex that could act as a marker for sites of DNA damage, directing assembly of subsequent DNA repair factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960746", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 747, "text": "Mfd may act through a translocase activity that rewinds upstream DNA, leading either to translocation or to release of RNA polymerase when the enzyme active site cannot continue elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086674", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 678, "text": "Recent structural studies of the bacterial transcription-repair coupling factor, Mfd, have revealed a modular architecture in which an ATP-dependent DNA-based motor is coupled to protein-protein interaction domains that can attach the motor to RNA polymerase and the DNA repair protein UvrA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17572090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086674", "endSection": "title" }, { "offsetInBeginSection": 456, "offsetInEndSection": 621, "text": "We also find that the transcription-repair coupling factor, Mfd, promotes direct restart of the fork following the collision by facilitating displacement of the RNAP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436399", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 612, "text": "We also found that the transcription-repair coupling factor Mfd promotes direct restart of the fork after the collision by facilitating displacement of the RNAP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110508", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 761, "text": "We show that Mfd-dependent TCR in bacteria involves the formation of a damage search complex that can detect lesions downstream of a stalled RNAP, and that the strand specificity of the accelerated repair pathway is independent of the requirement for a lesion to stall RNAP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24554077", "endSection": "abstract" }, { "offsetInBeginSection": 47, "offsetInEndSection": 202, "text": "coli by the Mfd protein, which dissociates transcription elongation complexes blocked at nonpairing lesions and mediates recruitment of DNA repair proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086674", "endSection": "abstract" } ] }, { "body": "What is the association between Generalized anxiety disorder and mortality risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12947243", "http://www.ncbi.nlm.nih.gov/pubmed/9133488", "http://www.ncbi.nlm.nih.gov/pubmed/1474300", "http://www.ncbi.nlm.nih.gov/pubmed/19321850", "http://www.ncbi.nlm.nih.gov/pubmed/23929442", "http://www.ncbi.nlm.nih.gov/pubmed/22549369", "http://www.ncbi.nlm.nih.gov/pubmed/11769822", "http://www.ncbi.nlm.nih.gov/pubmed/17450651", "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "http://www.ncbi.nlm.nih.gov/pubmed/12063146", "http://www.ncbi.nlm.nih.gov/pubmed/12490824" ], "ideal_answer": [ "Numerous studies have demonstrated that Generalized anxiety disorder is associated with increased mortality risk in different populations, including veterans and non demented elderly individuals. Anxiety disorders predict greater mortality, particularly when present with other psychiatric disorders. However, one study has found that generalized anxiety disorder was not associated with excess mortality in depressive elderly people." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009026", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306" ], "type": "summary", "id": "54f4914bd0d681a040000001", "snippets": [ { "offsetInBeginSection": 722, "offsetInEndSection": 1010, "text": "RESULTS: MDD and GAD were positively and significantly associated with all-cause and CVD mortality. The relationships between MDD and GAD and CVD mortality were no longer significant after adjustment for sociodemograhics, health status at entry, health behaviors, and other risk markers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19321850", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1537, "text": "In analyses comparing comorbidity and GAD and MDD alone, with neither diagnosis, comorbidity proved to be the strongest predictor of both all-cause and CVD mortality. CONCLUSION: GAD and MDD predict all-cause mortality in a veteran population after adjusting for a range of covariates. However, those with both GAD and MDD were at greatest risk of subsequent death, and it would seem that these disorders may interact synergistically to affect mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19321850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Anxiety disorders are prevalent and associated with an increase in morbidity and mortality, particularly when present with additional psychiatric disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17450651", "endSection": "abstract" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1480, "text": "ICD-10 GAD was related to an increased mortality rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22549369", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1515, "text": "Neither generalized anxiety nor mixed anxiety-depression are associated with excess mortality. Generalized anxiety disorder may even predict less mortality in depressive elderly people. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 393, "text": "Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12947243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Anxiety disorders are prevalent and associated with increased morbidity and mortality. Some chronic anxiety disorders, including generalized anxiety disorder (GAD), may be characterized by an underlying high level of anxiety on which exacerbations of symptoms are superimposed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12490824", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 160, "text": "Neither generalized anxiety nor mixed anxiety-depression are associated with excess mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 251, "text": "Generalized anxiety disorder may even predict less mortality in depressive elderly people.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 765, "text": "In women, mortality risk was increased for anxiety disorder and GAD in multivariate Cox models (hazard ratio (HR) = 1.53, 95% CI 1.02-2.27 and HR = 2.04, 95% CI 1.08-3.86 respectively), whereas for phobia it was nearly significant (HR = 1.52, 95% CI 0.94-2.47)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23929442", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1464, "text": "Generalized anxiety disorder may even predict less mortality in depressive elderly people", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1042, "text": "In generalized anxiety disorder and mixed anxiety-depression no significant excess mortality was found", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1591, "text": "The relation between generalized anxiety disorder and its possibly protective effect on mortality has to be further explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1373, "text": "Neither generalized anxiety nor mixed anxiety-depression are associated with excess mortality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998780", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1497, "text": "However, those with both GAD and MDD were at greatest risk of subsequent death, and it would seem that these disorders may interact synergistically to affect mortality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19321850", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by a monoclonal antibody Mepolizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21824072", "http://www.ncbi.nlm.nih.gov/pubmed/20021987", "http://www.ncbi.nlm.nih.gov/pubmed/25199060", "http://www.ncbi.nlm.nih.gov/pubmed/19929788", "http://www.ncbi.nlm.nih.gov/pubmed/22092535", "http://www.ncbi.nlm.nih.gov/pubmed/11496242", "http://www.ncbi.nlm.nih.gov/pubmed/16184589", "http://www.ncbi.nlm.nih.gov/pubmed/14699394", "http://www.ncbi.nlm.nih.gov/pubmed/21346698", "http://www.ncbi.nlm.nih.gov/pubmed/24424174", "http://www.ncbi.nlm.nih.gov/pubmed/14523040", "http://www.ncbi.nlm.nih.gov/pubmed/19264687", "http://www.ncbi.nlm.nih.gov/pubmed/19264686", "http://www.ncbi.nlm.nih.gov/pubmed/21958585", "http://www.ncbi.nlm.nih.gov/pubmed/12704348", "http://www.ncbi.nlm.nih.gov/pubmed/12870444", "http://www.ncbi.nlm.nih.gov/pubmed/24685200", "http://www.ncbi.nlm.nih.gov/pubmed/21348536", "http://www.ncbi.nlm.nih.gov/pubmed/15175031", "http://www.ncbi.nlm.nih.gov/pubmed/23257685", "http://www.ncbi.nlm.nih.gov/pubmed/20110057", "http://www.ncbi.nlm.nih.gov/pubmed/25199059", "http://www.ncbi.nlm.nih.gov/pubmed/21790283", "http://www.ncbi.nlm.nih.gov/pubmed/12406833", "http://www.ncbi.nlm.nih.gov/pubmed/20810155", "http://www.ncbi.nlm.nih.gov/pubmed/17872493", "http://www.ncbi.nlm.nih.gov/pubmed/23742015", "http://www.ncbi.nlm.nih.gov/pubmed/23844029", "http://www.ncbi.nlm.nih.gov/pubmed/15813818", "http://www.ncbi.nlm.nih.gov/pubmed/24322486", "http://www.ncbi.nlm.nih.gov/pubmed/22998420", "http://www.ncbi.nlm.nih.gov/pubmed/16462679", "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "http://www.ncbi.nlm.nih.gov/pubmed/19828470", "http://www.ncbi.nlm.nih.gov/pubmed/18298130", "http://www.ncbi.nlm.nih.gov/pubmed/19243381", "http://www.ncbi.nlm.nih.gov/pubmed/20513524", "http://www.ncbi.nlm.nih.gov/pubmed/18344568", "http://www.ncbi.nlm.nih.gov/pubmed/20565230", "http://www.ncbi.nlm.nih.gov/pubmed/16931891", "http://www.ncbi.nlm.nih.gov/pubmed/22901886", "http://www.ncbi.nlm.nih.gov/pubmed/23362812", "http://www.ncbi.nlm.nih.gov/pubmed/21443279", "http://www.ncbi.nlm.nih.gov/pubmed/23544105" ], "ideal_answer": [ "Mepolizumab is a humanized monoclonal antibody that binds to and inactivates interleukin-5 that has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma." ], "exact_answer": [ "interleukin-5" ], "concepts": [ "http://www.biosemantics.org/jochem#4002251" ], "type": "factoid", "id": "54d907c84b1fd0d33c000008", "snippets": [ { "offsetInBeginSection": 258, "offsetInEndSection": 438, "text": "Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25199060", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 704, "text": " Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25199059", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1231, "text": "Among developing therapies, biologics designed to block certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13 (lebrikizumab), have a greater chance of being used in the clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685200", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1454, "text": "Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424174", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 978, "text": " Recent results of the treatment of idiopathic hypereosinophilic syndrome (HES) with the anti-interleukin 5 monoclonal antibody mepolizumab showed its efficacy and manageable safety profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24322486", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 808, "text": "Individuals also received a segmental bronchoprovocation with allergen (SBP-Ag) 1 month before and after administering a single dose of mepolizumab (anti-IL-5 monoclonal antibody) to reduce airway EOS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23844029", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 919, "text": "For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23544105", "endSection": "title" }, { "offsetInBeginSection": 115, "offsetInEndSection": 255, "text": "Previous clinical trials have evaluated the efficacy and safety of mepolizumab, a monoclonal antibody against IL-5, in patients with asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23544105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "In this large (616 patients), double-blind, placebo-controlled, dose-ranging study of mepolizumab (a monoclonal antibody that blocks IL-5 binding to its receptor), patients were given placebo, 75-, 250- or 750-mg mepolizumab by intravenous infusion every 4 weeks for 1 year. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23362812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "BACKGROUND: We examined levels of hyaluronan, a matrix glycosaminoglycan and versican, a matrix proteoglycan, in the sputum of asthmatics treated with mepolizumab (anti-IL-5 monoclonal antibody) versus placebo to evaluate the utility of these measurements as possible biomarkers of asthma control and airway remodeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257685", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 526, "text": "Mepolizumab is a humanized monoclonal antibody that blocks binding of the key cytokine implicated specifically in eosinophil maturation and survival, interleukin-5, to its receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22998420", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 318, "text": "Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22901886", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 752, "text": "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1053, "text": "Two monoclonal antibodies have been designed to neutralize IL-5 (mepolizumab and reslizumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22092535", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 703, "text": "To date, two humanized monoclonal antibodies, mepolizumab and reslizumab, have been developed that bind to human IL-5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21824072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Mepolizumab (Bosatria(\u00ae), GlaxoSmithKline) is a biologic agent developed to treat asthma. It represents a humanized monoclonal antibody of IgG1 \u03ba type, which targets human IL-5 and thus prevents its interaction with the \u03b1-chain of the IL-5 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21790283", "endSection": "abstract" }, { "offsetInBeginSection": 1285, "offsetInEndSection": 1462, "text": "There has been a variable effect with the leukotriene receptor antagonist montelukast and promising early results with mepolizumab, a monoclonal antibody against interleukin-5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21443279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin-5 monoclonal antibody.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21348536", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Mepolizumab is a fully humanized monoclonal antibody (IgG1/\u03ba) targeting human interleukin-5 (IL-5), a key haematopoietin needed for eosinophil development and function. Mepolizumab blocks human IL-5 from binding to the \u03b1-chain of the IL-5 receptor complex on the eosinophil cell surface, thereby inhibiting IL-5 signalling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21348536", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1383, "text": "Recently, encouraging results of treatment with monoclonal antibody neutralizing IL-5, mepolizumab, have been published.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21346698", "endSection": "abstract" }, { "offsetInBeginSection": 1306, "offsetInEndSection": 1524, "text": "This manuscript reviews the available treatments for HES and the range of side-effects associated with long-term corticosteroid use, and then focuses on the anti-IL-5 monoclonal antibodies, mepolizumab and reslizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20565230", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1810, "text": "The therapeutic progress is primarily due to an explosion of biological therapies, particularly four of them very useful for internists (in an off label use) : Interleukin 1 inhibitors (anakinra, Canakinumab) to treat some auto inflammatory diseases (cryopirin associated periodic syndromes and deficency of interleukin 1 receptor antagonist), monoclonal antibody against interleukin 5 (mepolizumab) to treat some hypereosinophilic syndromes and Churg and Strauss angiitis, interleukin 6 inhibitiors to treat multifocal Castleman's disease and adult Still disease, a monoclonal antibody against vascular endothelial growth factor (Bevacizumab) to treat hereditary hemorrhagic telangiectasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110057", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 826, "text": " Besides steroid therapy, the anti-IL-5 monoclonal antibody mepolizumab is considered as a target therapy for L-HES.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20021987", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 475, "text": "Mepolizumab is a humanized monoclonal antibody (mAb) with potent IL-5 neutralizing effects that represents a potential treatment for eosinophilic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19929788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19828470", "endSection": "title" }, { "offsetInBeginSection": 183, "offsetInEndSection": 299, "text": "The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19828470", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 529, "text": "We studied the prednisone-sparing effect of mepolizumab, a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19264687", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 667, "text": "Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19264686", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1424, "text": "A recent study showed that a monoclonal antibody to IL-5, mepolizumab, reduced glucocorticoid therapy in HES patients who did not possess the FIP1L1-PDGFRA mutation while controlling eosinophilia and preventing recurrence or progression of tissue damage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19243381", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 579, "text": "METHODS: We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti-interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18344568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Mepolizumab: 240563, anti-IL-5 monoclonal antibody - GlaxoSmithKline, anti-interleukin-5 monoclonal antibody - GlaxoSmithKline, SB 240563.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18298130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Mepolizumab is an anti-interleukin-5 monoclonal antibody that is in clinical trials with GlaxoSmithKline (GSK) for the treatment of severe asthma, nasal polyposis and hypereosinophilic syndrome and eosinophilic oesophagitis (the latter two indications are classed as eosinophilia in the phase table). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18298130", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 480, "text": "A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17872493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16931891", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 346, "text": "Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16931891", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1357, "text": "Mepolizumab, an anti-IL-5 monoclonal antibody, currently being evaluated, seems promising. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16462679", "endSection": "abstract" }, { "offsetInBeginSection": 1261, "offsetInEndSection": 1389, "text": "These include imatinib mesylate, a tyrosine kinase inhibitor, and more recently, mepolizumab, an anti-IL-5 monoclonal antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16184589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15813818", "endSection": "title" }, { "offsetInBeginSection": 179, "offsetInEndSection": 273, "text": "A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15813818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Anti-IL-5 monoclonal antibody (mepolizumab) reduces baseline bronchial mucosal eosinophils and deposition of extracellular matrix proteins in the reticular basement membrane in mild asthma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15175031", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 677, "text": "Skin biopsies were performed in 24 atopic subjects at allergen- and diluent-injected sites before 6 and 48 h after, three infusions of a humanized, monoclonal antibody against IL-5 (mepolizumab) using a randomized double-blind, placebo-controlled design. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15175031", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 547, "text": "OBJECTIVE: We aimed to assess the safety and efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab) in patients with several forms of hyper-eosinophilic syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14699394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14699394", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 409, "text": "Bronchial biopsies were obtained before and after three infusions of a humanized, anti-IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14523040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "GlaxoSmithKline (formerly SmithKline Beecham) is developing mepolizumab (SB-240563), a monoclonal antibody directed against IL-5, as a potential treatment for asthma and atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12870444", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 748, "text": "METHODS: Blood, bone marrow, and airway mucosal biopsy specimens were examined before and after anti-IL-5 (mepolizumab) treatment of asthmatic individuals in a double-blind, placebo-controlled trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12704348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12704348", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "The role of eosinophils as effector cells in asthma pathogenesis has been questioned since an anti-interleukin (IL)-5 monoclonal antibody (mepolizumab), which depleted blood and sputum eosinophils, failed to inhibit allergen-induced bronchoconstriction and airway hyperresponsiveness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12406833", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 454, "text": "Mepolizumab (SB-240563), a humanized monoclonal antibody (mAb) specific for human IL-5, is currently in clinical trials for treatment of asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11496242", "endSection": "abstract" }, { "offsetInBeginSection": 2091, "offsetInEndSection": 2366, "text": "CONCLUSION: These studies demonstrate that chronic antagonism of IL-5 by mepolizumab in monkeys is safe and has the potential, through long-term reductions in circulating and tissue-resident eosinophils, to be beneficial therapy for chronic inflammatory respiratory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11496242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11496242", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Mepolizumab is a fully humanized monoclonal antibody (IgG1/\ufffd) targeting human interleukin-5 (IL-5), a key haematopoietin needed for eosinophil development and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21348536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "BACKGROUND: Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor \ufffd fusion (F/P)-negative hypereosinophilic syndrome (HES).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Mepolizumab is a fully humanized monoclonal antibody (IgG1/\u03ba) targeting human interleukin-5 (IL-5), a key haematopoietin needed for eosinophil development and function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21348536", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 323, "text": "Mepolizumab blocks human IL-5 from binding to the \u03b1-chain of the IL-5 receptor complex on the eosinophil cell surface, thereby inhibiting IL-5 signalling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21348536", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 825, "text": "Besides steroid therapy, the anti-IL-5 monoclonal antibody mepolizumab is considered as a target therapy for L-HES", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20021987", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 750, "text": "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "endSection": "abstract" } ] }, { "body": "Which is the major symptom of the Doose syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24696509", "http://www.ncbi.nlm.nih.gov/pubmed/22266062", "http://www.ncbi.nlm.nih.gov/pubmed/18990309", "http://www.ncbi.nlm.nih.gov/pubmed/12073789", "http://www.ncbi.nlm.nih.gov/pubmed/21396429", "http://www.ncbi.nlm.nih.gov/pubmed/23159713", "http://www.ncbi.nlm.nih.gov/pubmed/1396420", "http://www.ncbi.nlm.nih.gov/pubmed/19049588", "http://www.ncbi.nlm.nih.gov/pubmed/20722665", "http://www.ncbi.nlm.nih.gov/pubmed/17105462", "http://www.ncbi.nlm.nih.gov/pubmed/20472190", "http://www.ncbi.nlm.nih.gov/pubmed/8214350", "http://www.ncbi.nlm.nih.gov/pubmed/8243377", "http://www.ncbi.nlm.nih.gov/pubmed/20301494", "http://www.ncbi.nlm.nih.gov/pubmed/22780699", "http://www.ncbi.nlm.nih.gov/pubmed/9184597", "http://www.ncbi.nlm.nih.gov/pubmed/10768159", "http://www.ncbi.nlm.nih.gov/pubmed/8891396", "http://www.ncbi.nlm.nih.gov/pubmed/22322415", "http://www.ncbi.nlm.nih.gov/pubmed/21351810", "http://www.ncbi.nlm.nih.gov/pubmed/8753132", "http://www.ncbi.nlm.nih.gov/pubmed/23941843", "http://www.ncbi.nlm.nih.gov/pubmed/2115971" ], "ideal_answer": [ "Myoclonic astatic epilepsy is the major symptom of the Doose syndrome, which is a difficult to treat idiopathic generalized epilepsy of early childhood." ], "exact_answer": [ "myoclonic astatic epilepsy" ], "type": "factoid", "id": "550342a8f8aee20f27000002", "snippets": [ { "offsetInBeginSection": 816, "offsetInEndSection": 1011, "text": "KD is particularly effective in myoclonic astatic epilepsy (MAE; Doose Syndrome) and West syndrome with 100% and 81.25% of the patients having a greater than 50% seizure reduction, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23941843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Myoclonic astatic epilepsy (Doose syndrome) - a lamotrigine responsive epilepsy?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159713", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "PURPOSE: Myoclonic astatic epilepsy (MAE, Doose syndrome) is a difficult to treat idiopathic generalized epilepsy of early childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Herman Doose first described the generalized childhood epilepsy syndrome of myoclonic astatic epilepsy (MAE) in 1970, attributing a genetic cause from this first description. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22780699", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 704, "text": "RECENT FINDINGS: In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22322415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "First long-term experience with the orphan drug rufinamide in children with myoclonic-astatic epilepsy (Doose syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266062", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "INTRODUCTION: We evaluated the long-term efficacy and tolerability of the orphan drug rufinamide (RUF) in children with pharmacoresistant myoclonic-astatic epilepsy (MAE, Doose syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Mutations in SCN1A gene, encoding the voltage-gated sodium channel \u03b11-subunit, are found to be associated with severe myoclonic epilepsy in infancy or Dravet syndrome (DS), but only rarely with the myoclonic astatic epilepsy (MAE, or Doose syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21396429", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1305, "text": "The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21351810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Doose syndrome (myoclonic-astatic epilepsy): 40 years of progress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20722665", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Doose syndrome, otherwise traditionally known as myoclonic-astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20722665", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 769, "text": "Of 38 patients, 22 had Lennox-Gastaut syndrome (58%); 6 had myoclonic-astatic epilepsy of Doose (16%); 5 had symptomatic generalized epilepsy, not otherwise specified (13%); and 5 had symptomatic localization-related epilepsy (13%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20472190", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1080, "text": "With felbamate treatment, 6 patients (16%) became seizure free, including 4 of the 6 patients with myoclonic-astatic epilepsy of Doose; 24 patients (63%) had a greater than 50% reduction in seizure frequency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20472190", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 738, "text": "Less commonly observed phenotypes include myoclonic-astatic epilepsy (MAE or Doose syndrome), Lennox-Gastaut syndrome (LGS), infantile spasms, and vaccine-related encephalopathy and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301494", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 343, "text": "This includes syndromes with multiple etiologies, including Lennox-Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau-Kleffner syndrome; and idiopathic epilepsies, such as myoclonic-astatic (Doose) epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19049588", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 303, "text": "It should be considered early in the treatment of Dravet syndrome and myoclonic-astatic epilepsy (Doose syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18990309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The purpose of this article is to present a short review of the natural history of myoclonic astatic epilepsy (MAE; Doose syndrome) and the Lennox-Gastaut syndrome (LGS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17105462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "[Clinical case of the month. Myoclonic-astatic epilepsy in a young child (MAE) or Doose syndrome].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12073789", "endSection": "title" }, { "offsetInBeginSection": 601, "offsetInEndSection": 771, "text": "His refractory epilepsy which started 7 years ago shares symptoms and signs of both epilepsy with myoclonic-astatic seizures (Doose Syndrome) and Lennox-Gastaut Syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10768159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "PURPOSE: Before 1986, the spectrum of childhood epilepsies, including Lennox-Gastaut syndrome (LGS) and Doose syndrome (DS), known collectively as \"epilepsia myoclonica astatica,\" was believed to represent a single disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9184597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "We reported a 7-year-old girl with myoclonic-astatic epilepsy of early childhood (Doose syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8753132", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 1005, "text": "Other myoclonic epilepsy syndromes with onset in the first year of life (Aicardi's Neonatal (Early) Myoclonic Encephalopathy, West's Syndrome, Dravet's Severe Myoclonic Epilepsy, and Dravet's Benign Myoclonic Epilepsy of Infancy), in early childhood (Lennox-Gastaut-Dravet Syndrome, Myoclonic Variant of Lennox Gastaut Dravet Syndrome, Myoclonic-Astatic Epilepsy of Doose, Benign Myoclonic Epilepsies (BME), or even in late childhood (Childhood Absence Epilepsy with myoclonias, vs. Myoclonic Absence Epilepsy) are probably genetically complex diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8891396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "A study of epileptic drop attacks (EDA) by simultaneous video-polygraphic recordings was carried out in one epileptic patient with myoclonic astatic seizures (Doose syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8214350", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 981, "text": "A number of variants or atypical forms have been proposed. As a result, differential diagnosis presents a major challenge and includes specific generalized epilepsies, i.e., metabolic or inflammatory; secondarily generalized epilepsies, i.e., those arising from the frontal lobe; and severe forms of idiopathic generalized epilepsy, i.e., Doose syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8243377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Video-EEG analysis of drop seizures in myoclonic astatic epilepsy of early childhood (Doose syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1396420", "endSection": "title" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1204, "text": " The clinical and EEG pattern, the high familial incidence are shared by the Doose syndrome, of which the present series seems to be a subgroup, as are other well-defined syndromes: benign and severe myoclonic epilepsies of infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2115971", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1304, "text": "The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21351810", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1302, "text": "The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21351810", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 770, "text": "His refractory epilepsy which started 7 years ago shares symptoms and signs of both epilepsy with myoclonic-astatic seizures (Doose Syndrome) and Lennox-Gastaut Syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10768159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Doose syndrome, otherwise traditionally known as myoclonic-astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20722665", "endSection": "abstract" } ] }, { "body": "Have mutations in the GARS gene been identified to cause Charcot-Marie-Tooth Disease Type 2D (CMT2D)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17035524", "http://www.ncbi.nlm.nih.gov/pubmed/23990368", 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}, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18458984", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18458985", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18468134", "o": "MeSH" } ], "ideal_answer": [ "Charcot-Marie-Tooth disease type 2D (CMT2D) is caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/SYG_RAT", "http://www.uniprot.org/uniprot/SYG_HUMAN", "http://www.uniprot.org/uniprot/SYG_PONAB" ], "type": "yesno", "id": "52b2ecd34003448f55000003", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Mutations in the GARS gene cause Charcot-Marie-Tooth 2D and distal spinal muscular atrophy type V - allelic disorders characterized by predominantly distal upper extremity weakness and atrophy, typically beginning during the second decade of life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22462675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22144914", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 854, "text": "The 13 genes known to be associated with the CMT2 subtypes are KIF1B (CMT2A1), MFN2 (CMT2A2), RAB7A (formerly RAB7) (CMT2B), LMNA (CMT2B1), MED25 (CMT2B2), TRPV4 (CMTC), GARS (CMT2D), NEFL (CMT2E/1F), HSPB1 (CMT2F), MPZ (CMT2I/J), GDAP1 (CMT2H/K), HSPB8 (CMT2L), and AARS (CMT2N). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301462", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1154, "text": " The diagnosis of GARS-associated axonal neuropathy is based on clinical findings, electromyography (EMG), and molecular genetic testing of GARS, encoding glycyl-tRNA synthetase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "Sporadic juvenile muscular atrophy of the distal upper extremity or Hirayama's disease (HD) and autosomal dominant motor distal neuronopathy/axonopathy (CMT2D/dSMA-V), produced by glycyl-tRNA synthetase (GARS) gene mutations, share some clinical features including: young age of onset, predilection for the distal upper extremity, asymmetry, sparing of proximal muscles and unusual cold sensitivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412816", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 394, "text": "Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17663003", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 313, "text": "We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982418", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 632, "text": "Missense mutations in the glycyl-tRNA synthetase (GARS) gene have been recently reported in families with either dHMN-V, CMT2D, or both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16769947", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1359, "text": "Based on the presence or absence of sensory changes, the disease phenotype was initially defined as distal spinal muscular atrophy type V (dSMA-V) in three families, Charcot-Marie-Tooth disease type 2D (CMT2D) in a single family, and as either dSMA-V or CMT2D in patients of another large family. Linkage to chromosome 7p15 and the presence of disease-associated heterozygous GARS mutations have been identified in patients from each of the five studied families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16014653", "endSection": "abstract" } ] }, { "body": "Which treatment leads to an increase in neutrophil counts in severe congenital neutropenia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7529539", "http://www.ncbi.nlm.nih.gov/pubmed/2683920", "http://www.ncbi.nlm.nih.gov/pubmed/1705835", "http://www.ncbi.nlm.nih.gov/pubmed/1689595", "http://www.ncbi.nlm.nih.gov/pubmed/10779444", "http://www.ncbi.nlm.nih.gov/pubmed/21052952", "http://www.ncbi.nlm.nih.gov/pubmed/16822461" ], "ideal_answer": [ "In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections ", "In patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050590" ], "type": "summary", "id": "550313aae9bde6963400001f", "snippets": [ { "offsetInBeginSection": 173, "offsetInEndSection": 441, "text": "This chapter focuses on cyclic and congenital neutropenia, two very interesting and rare hematological conditions causing severe chronic neutropenia. Both disorders respond well to treatment with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21052952", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1474, "text": "Data on more than 600 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) demonstrate that, regardless of the particular CN subtype, more than 95% of these patients respond to recombinant human (rHu)G-CSF with ANCs that can be maintained above 1.0 x 10(9)/L.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16822461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7529539", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 380, "text": "In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7529539", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 660, "text": "A sustained ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10 cyclic neutropenia patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7529539", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 433, "text": "We examined peripheral blood mononuclear cells (PBMC) of SCN patients who demonstrated normalization of their blood neutrophil counts in a phase II clinical study with recombinant human granulocyte colony-stimulating factor (rhG-CSF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1705835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia secondary to a maturational arrest at the level of promyelocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1689595", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1170, "text": "In contrast to rhGM-CSF treatment, all five patients responded to rhG-CSF during the first 6 weeks of treatment with an increase in the ANC to above 1,000/microL. The level of ANC could be maintained during maintenance treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1689595", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 470, "text": "Treatment of these patients with granulocyte colony-stimulating factor (G-CSF) leads to a significant increase in circulating neutrophils and a reduction in infection-related events in more than 95% of the patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10779444", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1333, "text": "In patients with chronic neutropenia, rhGM-CSF may increase neutrophil counts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2683920", "endSection": "abstract" } ] }, { "body": "Which genes are affected in ROMANO-WARD syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10482963", "http://www.ncbi.nlm.nih.gov/pubmed/15511625", "http://www.ncbi.nlm.nih.gov/pubmed/20981542", "http://www.ncbi.nlm.nih.gov/pubmed/19490272", "http://www.ncbi.nlm.nih.gov/pubmed/9511785", "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "http://www.ncbi.nlm.nih.gov/pubmed/12388934", "http://www.ncbi.nlm.nih.gov/pubmed/10953551", "http://www.ncbi.nlm.nih.gov/pubmed/17560885", "http://www.ncbi.nlm.nih.gov/pubmed/10973849", "http://www.ncbi.nlm.nih.gov/pubmed/16931984", "http://www.ncbi.nlm.nih.gov/pubmed/16981927", "http://www.ncbi.nlm.nih.gov/pubmed/9848024", "http://www.ncbi.nlm.nih.gov/pubmed/9641694", "http://www.ncbi.nlm.nih.gov/pubmed/10613047", "http://www.ncbi.nlm.nih.gov/pubmed/20301308", "http://www.ncbi.nlm.nih.gov/pubmed/10868746", "http://www.ncbi.nlm.nih.gov/pubmed/20850564", "http://www.ncbi.nlm.nih.gov/pubmed/19540844", "http://www.ncbi.nlm.nih.gov/pubmed/9791861", "http://www.ncbi.nlm.nih.gov/pubmed/18752142", "http://www.ncbi.nlm.nih.gov/pubmed/16831322", "http://www.ncbi.nlm.nih.gov/pubmed/14756674", "http://www.ncbi.nlm.nih.gov/pubmed/23000022", "http://www.ncbi.nlm.nih.gov/pubmed/12442276", "http://www.ncbi.nlm.nih.gov/pubmed/10898405", "http://www.ncbi.nlm.nih.gov/pubmed/10220144", "http://www.ncbi.nlm.nih.gov/pubmed/10560244", "http://www.ncbi.nlm.nih.gov/pubmed/15306731", "http://www.ncbi.nlm.nih.gov/pubmed/22461049", "http://www.ncbi.nlm.nih.gov/pubmed/11216980" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2988", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/KCNQ1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/KCNQ1", "o": "KCNQ1" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2988", "o": "Long QT syndrome-1, 192500" } ], "ideal_answer": [ "The genes involved in ROMANO-WARD syndrome are KCNQ1, KCNE1, KCNE2, KCNH2, SCN5A, CAV3, SCN4B, AKAP9, SNTA1, KCNJ5 and Ankyrin-B." ], "exact_answer": [ [ "KCNQ1", "KVLQT1", "KCNA9" ], [ "KCNE1" ], [ "KCNE2" ], [ "KCNH2", "HERG" ], [ "SCN5A" ], [ "CAV3" ], [ "SCN4B" ], [ "AKAP9" ], [ "SNTA1" ], [ "KCNJ5" ], [ "Ankyrin-B gene" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029597", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "list", "id": "52eea509c8da89891000000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Long QT syndrome (LQTS) 1 is the most common type of inherited LQTS and is linked to mutations in the KCNQ1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23000022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "This report describes a three-generation family with a severe phenotype of long-QT syndrome-1 (LQTS-1) caused by a single nucleotide mutation in the KQT-like, voltage-gated potassium channel-1 gene (KCNQ1; MIM 607542).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981542", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 297, "text": "Mutations in a cardiac voltage-gated potassium channel, KCNQ1, account for the most common form of LQTS, LQTS1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19540844", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 684, "text": "Nine patients were diagnosed with LQT1 and nine with LQT2. The other six individuals were healthy, with no symptoms characteristic for prolonged QT syndrome, but came from families with confirmed disease occurrence. The study was conducted on members of four families. In order to search for mutations (using mSSCP and sequencing), genomic DNA was obtained from patients to determine the expression levels of the genes KCNQ1 and KCNH2 (HERG), involved in the occurrence of clinical signs of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461049", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1495, "text": "Diagnosis of RWS is established by prolongation of the QTc interval in the absence of specific conditions known to lengthen it (for example, QT-prolonging drugs) and/or molecular genetic testing of the genes known to be associated with RWS, of which KCNQ1 (locus name LQT1), KCNH2 (locus name LQT2) and SCN5A (locus name LQT3) are the most common. Other, less frequently involved genes are KCNE1 (locus name LQT5), KCNE2 (locus name LQT6), CAV3 (locus name LQT9), SCN4B (locus name LQT10), AKAP9 (locus name LQT11), SNTA1 (locus name LQT12) and KCNJ5 (locus name LQT13).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301308", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 84, "text": "Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19490272", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 267, "text": "Congenital LQTS is most frequently caused by mutations in KCNQ1 (Kv7.1), whereas drug-induced LQTS is a consequence of HERG (human ether-a-go-go-related gene) channel inhibition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16931984", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 300, "text": "Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 425, "text": "Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15511625", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 681, "text": "Seven family members were carriers of two amino acid alterations in cis (V254M-V417M) in the cardiac potassium channel gene KCNQ1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14756674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "KCNQ1 (formerly called KVLQT1) is a Shaker-like voltage-gated potassium channel gene responsible for the LQT1 sub-type of LQTS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12388934", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 306, "text": "Five genes have been implicated in Romano-Ward syndrome, the autosomal dominant form of LQTS: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10973849", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 313, "text": "It usually is inherited as an autosomal dominant trait (Romano-Ward syndrome). The primary defect in LQT1 is a mutation in KVLQT1, a gene that encodes the pore-forming alpha-subunit of a K+ channel. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10868746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "Romano-Ward syndrome is an autosomal dominant long-QT syndrome (LQTS) that predisposes affected individuals to sudden death from tachyarrhythmias. We investigated the molecular basis of LQTS in a Taiwanese kindred. Clinical and genetic analyses revealed that a mutation was linked to the human ether-a-go-go-related gene (HERG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10560244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "We describe a Swedish family with the proband and his brother suffering from severe Romano-Ward syndome (RWS) associated with compound heterozygosity for two mutations in the KVLQT1 (also known as KCNQ1 and KCNA9)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10482963", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 895, "text": "The cardiac sodium channel gene, SCN5A, is also mutated in some Romano-Ward cases to produce defects in INa, the cardiac inward Na+ current. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9848024", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1511, "text": "These findings provide the first evidence for a recessive form of the Romano-Ward long-QT syndrome and indicate that homozygous mutations on KVLQT1 do not invariably produce the Jervell and Lange-Nielsen syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9641694", "endSection": "abstract" } ] }, { "body": "Does melanoma occur in people of African origin ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1920508", "http://www.ncbi.nlm.nih.gov/pubmed/20415670", "http://www.ncbi.nlm.nih.gov/pubmed/8260178", "http://www.ncbi.nlm.nih.gov/pubmed/19538377", "http://www.ncbi.nlm.nih.gov/pubmed/19450404", "http://www.ncbi.nlm.nih.gov/pubmed/475965", "http://www.ncbi.nlm.nih.gov/pubmed/15540891", "http://www.ncbi.nlm.nih.gov/pubmed/12883369", "http://www.ncbi.nlm.nih.gov/pubmed/1135705", "http://www.ncbi.nlm.nih.gov/pubmed/876685", "http://www.ncbi.nlm.nih.gov/pubmed/8000657", "http://www.ncbi.nlm.nih.gov/pubmed/8402099", "http://www.ncbi.nlm.nih.gov/pubmed/1138394", "http://www.ncbi.nlm.nih.gov/pubmed/5776549", "http://www.ncbi.nlm.nih.gov/pubmed/1156726", "http://www.ncbi.nlm.nih.gov/pubmed/18227705", "http://www.ncbi.nlm.nih.gov/pubmed/10461463", "http://www.ncbi.nlm.nih.gov/pubmed/97949", "http://www.ncbi.nlm.nih.gov/pubmed/11205232" ], "ideal_answer": [ "Yes. Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians. The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018326", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.disease-ontology.org/api/metadata/DOID:4159", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545" ], "type": "yesno", "id": "515df6f2298dcd4e5100002d", "snippets": [ { "offsetInBeginSection": 109, "offsetInEndSection": 174, "text": "ALM is the most common type of melanoma amongst Asians, Africans,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20415670", "endSection": "sections.0" }, { "offsetInBeginSection": 261, "offsetInEndSection": 442, "text": "ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20415670", "endSection": "sections.0" }, { "offsetInBeginSection": 195, "offsetInEndSection": 259, "text": "We present four albinos with histologic diagnoses of skin cancer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19538377", "endSection": "sections.0" }, { "offsetInBeginSection": 571, "offsetInEndSection": 633, "text": "Four Nigerian albinos (two men and two women) with skin cancer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19538377", "endSection": "sections.0" }, { "offsetInBeginSection": 768, "offsetInEndSection": 933, "text": "The sites of the lesions included the head [squamous cell carcinoma (SCC) in two patients and basal cell carcinoma (BCC) in one patient] and the upper limb (melanoma", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19538377", "endSection": "sections.0" }, { "offsetInBeginSection": 386, "offsetInEndSection": 464, "text": "wenty-nine patients (18 males and 11 females) with skin cancer were identified", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450404", "endSection": "sections.0" }, { "offsetInBeginSection": 634, "offsetInEndSection": 785, "text": "Kaposi sarcoma associated with HIV represented 81.8 percent of KS cases found. Squamous cell carcinoma (SCC) ranked second and malignant melanoma third", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450404", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18227705", "endSection": "sections.0" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1666, "text": "In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18227705", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best of our knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenital giant hairy nevus is probably the first (in an accessible literature) in a black African child.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15540891", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Malignant melanomas in black Africans are predominantly located on the lower extremities", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11205232", "endSection": "sections.0" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1335, "text": "Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11205232", "endSection": "sections.0" }, { "offsetInBeginSection": 453, "offsetInEndSection": 724, "text": "Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10461463", "endSection": "sections.0" }, { "offsetInBeginSection": 727, "offsetInEndSection": 966, "text": "Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10461463", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 63, "text": "Scant data exists on melanoma in blacks from Africa", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8000657", "endSection": "sections.0" }, { "offsetInBeginSection": 582, "offsetInEndSection": 907, "text": "The mean age at presentation of the 39 women and 24 men was 60.5 years (range of 30 to 85 years), with a peak incidence in the sixth decade. The foot was the most common site of disease (45 patients). Seven patients had subungual melanoma, seven had primary mucosal lesions, and in six, the primary lesion could not be found.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8000657", "endSection": "sections.0" }, { "offsetInBeginSection": 1663, "offsetInEndSection": 1801, "text": "The poor prognosis in black patients in South Africa is the result of delayed presentation with thick primary lesions and advanced disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8000657", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The outcome of treatment in 40 black patients (27 women, 13 men; mean age 62.9 years) with plantar melanoma over a 13-year period was analysed", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8402099", "endSection": "sections.0" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1089, "text": "Delay in presentation and locally advanced disease may explain the poor prognosis of plantar melanoma in black South Africans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8402099", "endSection": "sections.0" }, { "offsetInBeginSection": 171, "offsetInEndSection": 537, "text": "Eighteen cases of malignant skin tumors seen at the University of Port Harcourt Teaching Hospital over 3 years (1984 to 1987) were analyzed for diagnoses, site of tumors, sex, and age. Seven patients (39%) had malignant melanomas affecting only the soles of the feet, while the same number had squamous cell carcinomas widely distributed in various parts of the body", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1920508", "endSection": "sections.0" }, { "offsetInBeginSection": 313, "offsetInEndSection": 454, "text": "Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/475965", "endSection": "sections.0" }, { "offsetInBeginSection": 511, "offsetInEndSection": 729, "text": "Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/475965", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Pathological features of twenty-one cases of malignant melanoma studied in the University of Nigeria Teaching Hospital, Enugu during the period January, 1974 to December, 1975 are presented. Malignant melanoma accounted for 2.4% of all tumours and 4.5% of all malignant tumours, greatest age incidence being in the fifth to seventh decades.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/97949", "endSection": "sections.0" }, { "offsetInBeginSection": 423, "offsetInEndSection": 563, "text": "81% melanomas occurred on the sole of feet validating the hypothesis that the pigmented skin in Africans is resistant to malignant melanoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/97949", "endSection": "sections.0" }, { "offsetInBeginSection": 182, "offsetInEndSection": 319, "text": "This paper reports the incidence of this lesion in association with invasive malignant melanomas of the feet and hands of Black Africans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/876685", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Follow-up data (over a 3-year period) and the histological appearances of primary lesion were studied and related in 40 Black patients with malignant melanoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1138394", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Malignant melanoma of the skin in Blacks in formidable and sinister tumour.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1135705", "endSection": "sections.0" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1278, "text": "The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1135705", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Twenty-one cases of malignant melanoma occurring in the Igbos of Nigeria have been analysed. The site of predilection is the sole of the foot. This result supports the conclusion that Negroes tend to have the disease in the non-pigmented parts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1156726", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/5776549", "endSection": "sections.0" } ] }, { "body": "What is the effect of resveratrol on mTOR activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23272906", "http://www.ncbi.nlm.nih.gov/pubmed/23211629", "http://www.ncbi.nlm.nih.gov/pubmed/22242130", "http://www.ncbi.nlm.nih.gov/pubmed/21966552", "http://www.ncbi.nlm.nih.gov/pubmed/24060150", "http://www.ncbi.nlm.nih.gov/pubmed/22530672", "http://www.ncbi.nlm.nih.gov/pubmed/23680031", "http://www.ncbi.nlm.nih.gov/pubmed/21179458", "http://www.ncbi.nlm.nih.gov/pubmed/22269797", "http://www.ncbi.nlm.nih.gov/pubmed/22029423", "http://www.ncbi.nlm.nih.gov/pubmed/21168265", "http://www.ncbi.nlm.nih.gov/pubmed/19108833", "http://www.ncbi.nlm.nih.gov/pubmed/19827268", "http://www.ncbi.nlm.nih.gov/pubmed/19471118", "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "http://www.ncbi.nlm.nih.gov/pubmed/23248098", "http://www.ncbi.nlm.nih.gov/pubmed/25448084", "http://www.ncbi.nlm.nih.gov/pubmed/20169165" ], "ideal_answer": [ "Resveratrol (RSV) inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR.", "Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human cells. It has been found that resveratrol targets multiple components of the phosphatidylinositol 3- kinase(PI3K)/Akt and mTOR signaling pathways, including PI3K, Akt, PTEN, and DEPTOR, suggesting that this natural compound and its derivatives may offer a promising new cancer treatment." ], "concepts": [ "http://www.uniprot.org/uniprot/MTOR_MOUSE", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://www.biosemantics.org/jochem#4272358" ], "type": "summary", "id": "551177626a8cde6b72000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "title" }, { "offsetInBeginSection": 226, "offsetInEndSection": 359, "text": "Here, we show that RSV inhibits insulin- and leucine-stimulated mTOR signaling in C2C12 fibroblasts via a Sirt1-independent mechanism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 601, "text": "Treating C2C12 cells with RSV dramatically inhibited insulin-stimulated Akt, S6 kinase, and 4E-BP1 phosphorylation but had little effect on tyrosine phosphorylation of the insulin receptor and activation of the p44/42 MAPK signaling pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 790, "text": "RSV treatment also partially blocked mTOR and S6 kinase phosphorylation in TSC1/2-deficient mouse embryonic fibroblasts, suggesting the presence of an inhibitory site downstream of TSC1/2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1396, "text": "Taken together, our studies reveal that RSV inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 824, "text": "Recent studies suggest that modulation of the mTOR signalling pathway could play an important role in mediating the beneficial effects of RSV. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24060150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108833", "endSection": "title" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1299, "text": "esveratrol blocked the oxLDL-induced phosphorylation and activation of the PI3K/Akt/mTOR/p70S6K pathway and strongly inhibited both the DNA synthesis and proliferation of SMC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19471118", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Here we demonstrated that, at cytostatic, near-toxic concentrations, resveratrol inhibited S6 phosphorylation and prevented the senescence morphology in human cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19471118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19827268", "endSection": "title" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1011, "text": "On the other hand, RSV significantly increased the association between mTOR and its inhibitor, DEPTOR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Resveratrol inhibits mTOR signaling by targeting DEPTOR", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21966552", "endSection": "title" }, { "offsetInBeginSection": 206, "offsetInEndSection": 502, "text": "Recent studies suggest that suppressing the signaling pathway mediated by mTOR, a well-known energy sensor that integrates various hormonal, nutrient and environmental signals to regulate cell growth, metabolism and survival, could play an important role in mediating the beneficial effect of RSV", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21966552", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269797", "endSection": "title" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1018, "text": "Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22530672", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21168265", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "title" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1681, "text": "Consistent with the in vitro findings, resveratrol intervention in the PTEN knockout mouse model was associated with reduction in the prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248098", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 546, "text": "Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21179458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108833", "endSection": "title" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1310, "text": "Resveratrol also alleviated the PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and up-regulation of PTEN expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25448084", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1272, "text": "Resveratrol blocked the oxLDL-induced phosphorylation and activation of the PI3K/Akt/mTOR/p70S6K pathway and strongly inhibited both the DNA synthesis and proliferation of SMC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108833", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 825, "text": "Resveratrol reduced phosphorylation of ribosomal protein S6 and the mTOR inhibitor rapamycin further enhanced resveratrol-induced cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19827268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19827268", "endSection": "title" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1019, "text": "Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269797", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 695, "text": "The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20169165", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1257, "text": "We conclude that resveratrol is an inhibitor of global protein synthesis, and that this effect is mediated through modulation of mTOR-dependent and independent signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22242130", "endSection": "abstract" }, { "offsetInBeginSection": 732, "offsetInEndSection": 888, "text": "RSV treatment has no effect on the expression levels of mTOR, raptor and DEPTOR, but greatly promotes the interaction between mTOR and its inhibitor DEPTOR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21966552", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1397, "text": "Taken together, our studies reveal that RSV inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1184, "text": "Furthermore, the inhibitory effect of RSV on leucine-stimulated mTOR signaling was greatly reduced in cells in which the expression levels of DEPTOR were suppressed by RNAi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20851890", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1688, "text": "Consistent with the in vitro findings, resveratrol intervention in the PTEN knockout mouse model was associated with reduction in the prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248098", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 694, "text": "The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20169165", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1298, "text": "However, most frequently, RSV is found to inhibit the activity of the mTOR pathway proteins, and to activate AMPK and LKB1, which can suppress mTOR signalling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24060150", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 557, "text": "Over the past few years, numerous studies have suggested that suppressing the activity of mammalian target of rapamycin (mTOR), a critical regulator of cell metabolism, growth, and proliferation, may provide a key mechanism underlying the anticarcinogenic properties of resveratrol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272906", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1628, "text": "Resveratrol blocks specifically this pathway, thereby inhibiting oxLDL-induced SMC proliferation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108833", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 300, "text": "Resveratrol causes cell cycle arrest and induces apoptotic cell death in various types of cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19827268", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 575, "text": "Resveratrol decreased both the expression and phosphorylation of Akt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19827268", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 119, "text": " Modulation of the AMPK, Akt and mTOR pathways", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22029423", "endSection": "title" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1097, "text": "RSV (2.5-5 \u03bcM) inhibited clonogenic survival of PC3 and 22RV1 cells but not of normal prostate PNT1A cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22029423", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1513, "text": "RSV enhanced IR-activation of ATM and AMPK but inhibited basal and IR-induced phosphorylation of Akt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22029423", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1755, "text": "Our results suggest that RSV arrests cell cycle, promotes apoptosis and sensitizes PrCa cells to IR likely through a desirable dual action to activate the ATM-AMPK-p53-p21(cip1)/p27(kip1) and inhibit the Akt signalling pathways", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22029423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Resveratrol pre-treatment reduces early inflammatory responses induced by status epilepticus via mTOR signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23211629", "endSection": "title" }, { "offsetInBeginSection": 276, "offsetInEndSection": 558, "text": "Over the past few years, numerous studies have suggested that suppressing the activity of mammalian target of rapamycin (mTOR), a critical regulator of cell metabolism, growth, and proliferation, may provide a key mechanism underlying the anticarcinogenic properties of resveratrol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272906", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 840, "text": "It has been found that resveratrol targets multiple components of the phosphatidylinositol 3- kinase(PI3K)/Akt and mTOR signaling pathways, including PI3K, Akt, PTEN, and DEPTOR, suggesting that this natural compound and its derivatives may offer a promising new cancer treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Autophagic cell death induced by resveratrol depends on the Ca(2+)/AMPK/mTOR pathway in A549 cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23680031", "endSection": "title" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1587, "text": "In conclusion, we demonstrate that resveratrol-induced A549 cell death was mediated by the process of autophagic cell death via Ca(2+)/AMPK-mTOR signaling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23680031", "endSection": "abstract" } ] }, { "body": "Are people with blood group O protected against severe Malaria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22771625", "http://www.ncbi.nlm.nih.gov/pubmed/15814030", "http://www.ncbi.nlm.nih.gov/pubmed/23071435", "http://www.ncbi.nlm.nih.gov/pubmed/22818742", "http://www.ncbi.nlm.nih.gov/pubmed/17959777" ], "ideal_answer": [ "It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14067", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001769", "http://www.disease-ontology.org/api/metadata/DOID:4176", "http://www.disease-ontology.org/api/metadata/DOID:12365", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008288", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001789" ], "type": "yesno", "id": "551ae6c564b14b4618000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Differential carbonylation of cytoskeletal proteins in blood group O erythrocytes: potential role in protection against severe malaria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22771625", "endSection": "title" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1460, "text": ". Our findings indicate a possible correlation between the protection against severe malaria in blood group O individuals and a specific pattern of 4-HNE-carbonylation of cytoskeleton proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22771625", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 314, "text": "There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071435", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1541, "text": "These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Blood group phenotypes A and B are risk factors for cerebral malaria in Odisha, India.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22818742", "endSection": "title" }, { "offsetInBeginSection": 519, "offsetInEndSection": 652, "text": "type O is significantly associated with protection against CM, patients with type A and B group had increased risk for developing CM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22818742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17959777", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 448, "text": "Malaria has been a major selective force on the human population, and several erythrocyte polymorphisms have evolved that confer resistance to severe malaria. Plasmodium falciparum rosetting, a parasite virulence phenotype associated with severe malaria, is reduced in blood group O erythrocytes compared with groups A, B, and AB, but the contribution of the ABO blood group system to protection against severe malaria has received little attention", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17959777", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 579, "text": "We hypothesized that blood group O may confer resistance to severe falciparum malaria through the mechanism of reduced rosetting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17959777", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1142, "text": "It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15814030", "endSection": "abstract" } ] }, { "body": "Which eye condition is managed by the athens protocol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21117539", "http://www.ncbi.nlm.nih.gov/pubmed/24763473", "http://www.ncbi.nlm.nih.gov/pubmed/25176050", "http://www.ncbi.nlm.nih.gov/pubmed/22347790", "http://www.ncbi.nlm.nih.gov/pubmed/24893359" ], "ideal_answer": [ "The athens protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking) was developed for the management of cornea blindness due to severe corneal scarring." ], "exact_answer": [ "Keratoconus", "cornea blindness due to severe corneal scarring" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10428", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005123" ], "type": "factoid", "id": "56bdc79bef6e394741000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763473", "endSection": "title" }, { "offsetInBeginSection": 1624, "offsetInEndSection": 1910, "text": "The Athens Protocol to arrest keratectasia progression and improve corneal regularity demonstrates safe and effective results as a keratoconus management option. Progressive potential for long-term flattening validates using caution in the surface normalization to avoid overcorrection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22347790", "endSection": "title" }, { "offsetInBeginSection": 8, "offsetInEndSection": 296, "text": " To evaluate the safety and efficacy of combined transepithelial topography-guided photorefractive keratectomy (PRK) therapeutic remodeling, combined with same-day, collagen cross-linking (CXL). This protocol was used for the management of cornea blindness due to severe corneal scarring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22347790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Management of corneal ectasia after LASIK with combined, same-day, topography-guided partial transepithelial PRK and collagen cross-linking: the athens protocol.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21117539", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Corneal refractive power and symmetry changes following normalization of ectasias treated with partial topography-guided PTK combined with higher-fluence CXL (the Athens Protocol).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24893359", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25176050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "To evaluate a series of patients with corneal ectasia after LASIK that underwent the Athens Protocol: combined topography-guided photorefractive keratectomy (PRK) to reduce or eliminate induced myopia and astigmatism followed by sequential, same-day ultraviolet A (UVA) corneal collagen cross-linking (CXL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21117539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 676, "text": "PURPOSE: To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes.SETTING: Private clinical practice, Athens, Greece.DESIGN: Comparative case series.METHODS: Fourier-domain anterior segment optical coherence tomography (AS-OCT) was used to obtain in vivo 3-dimensional epithelial thickness maps and center, superior, inferior, maximum, minimum, mean, midperipheral, and variability data.RESULTS: Group A comprised 175 treated keratoconic eyes (Athens protocol); Group B, 193 untreated keratoconic eyes; and Group C, 160 healthy eyes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25176050", "endSection": "abstract" }, { "offsetInBeginSection": 1614, "offsetInEndSection": 1789, "text": "CONCLUSIONS: The Athens Protocol to arrest keratectasia progression and improve corneal regularity demonstrates safe and effective results as a keratoconus management option. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes. Private clinical practice, Athens, Greece.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25176050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "To compare epithelial remodeling in keratoconic eyes that had photorefractive keratectomy and corneal collagen crosslinking (Athens protocol) with that in untreated keratoconic eyes and healthy eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25176050", "endSection": "abstract" } ] }, { "body": "What is the role of AMPK kinase in myocardial remodeling after myocardial infarction", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16155579", "http://www.ncbi.nlm.nih.gov/pubmed/23122726", "http://www.ncbi.nlm.nih.gov/pubmed/22344560", "http://www.ncbi.nlm.nih.gov/pubmed/22043210", "http://www.ncbi.nlm.nih.gov/pubmed/21572014" ], "ideal_answer": [ "AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI). \nAdiponectin protects the heart from ischemia-reperfusion injury through an AMPK-dependent mechanism.\nAMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:5843", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031588", "http://www.disease-ontology.org/api/metadata/DOID:5846", "http://www.disease-ontology.org/api/metadata/DOID:5847", "http://www.disease-ontology.org/api/metadata/DOID:5844", "http://www.disease-ontology.org/api/metadata/DOID:5845", "http://www.disease-ontology.org/api/metadata/DOID:10649", "http://www.disease-ontology.org/api/metadata/DOID:5848", "http://www.disease-ontology.org/api/metadata/DOID:5849", "http://www.uniprot.org/uniprot/AAKB2_RAT", "http://www.uniprot.org/uniprot/AAPK1_PIG", "http://www.uniprot.org/uniprot/AAPK2_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000480", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000481", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.uniprot.org/uniprot/AAPK2_HUMAN", "http://www.uniprot.org/uniprot/AAKB1_PIG", "http://www.uniprot.org/uniprot/AAKB1_PONAB", "http://www.uniprot.org/uniprot/AAPK2_PONAB", "http://www.uniprot.org/uniprot/AAKG1_BOVIN", "http://www.uniprot.org/uniprot/AAPK1_CAEEL", "http://www.uniprot.org/uniprot/AAPK1_MOUSE", "http://www.uniprot.org/uniprot/AAPK1_HUMAN", "http://www.uniprot.org/uniprot/AAKB1_BOVIN", "http://www.uniprot.org/uniprot/AAKG1_RAT", "http://www.uniprot.org/uniprot/AAKB1_HUMAN", "http://www.uniprot.org/uniprot/AAPK1_PONAB", "http://www.disease-ontology.org/api/metadata/DOID:5850", "http://www.disease-ontology.org/api/metadata/DOID:5853", "http://www.disease-ontology.org/api/metadata/DOID:5852", "http://www.uniprot.org/uniprot/AAKG1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:5854", "http://www.uniprot.org/uniprot/PRKAG_DICDI", "http://www.uniprot.org/uniprot/AAKB2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:10651", "http://www.uniprot.org/uniprot/AAKG_SCHPO", "http://www.disease-ontology.org/api/metadata/DOID:9408", "http://www.disease-ontology.org/api/metadata/DOID:5855", "http://www.uniprot.org/uniprot/AAPK1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056988", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056989", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004679", "http://www.uniprot.org/uniprot/AAPK2_MOUSE", "http://www.uniprot.org/uniprot/AAPK2_CAEEL", "http://www.uniprot.org/uniprot/AAKB1_MOUSE", "http://www.uniprot.org/uniprot/AAKG1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007238", "http://www.uniprot.org/uniprot/AAKB2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:5851", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380", "http://www.uniprot.org/uniprot/AAKB1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.uniprot.org/uniprot/AAKG_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000479" ], "type": "summary", "id": "516c0dc6298dcd4e5100006c", "snippets": [ { "offsetInBeginSection": 1142, "offsetInEndSection": 1280, "text": "These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16155579", "endSection": "sections.0" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1448, "text": "The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21572014", "endSection": "sections.0" }, { "offsetInBeginSection": 1625, "offsetInEndSection": 1766, "text": "Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21572014", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122726", "endSection": "sections.0" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1574, "text": "These results suggest that AMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart, which may indicate a link between AMPK and TLRs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122726", "endSection": "sections.0" } ] }, { "body": "What is the mechanism of action of solanezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24101429", "http://www.ncbi.nlm.nih.gov/pubmed/21784350", "http://www.ncbi.nlm.nih.gov/pubmed/21868184", "http://www.ncbi.nlm.nih.gov/pubmed/24353405", "http://www.ncbi.nlm.nih.gov/pubmed/24063020", "http://www.ncbi.nlm.nih.gov/pubmed/22482074", "http://www.ncbi.nlm.nih.gov/pubmed/21504387", "http://www.ncbi.nlm.nih.gov/pubmed/22848160", "http://www.ncbi.nlm.nih.gov/pubmed/24259408", "http://www.ncbi.nlm.nih.gov/pubmed/22506132", "http://www.ncbi.nlm.nih.gov/pubmed/23582316", "http://www.ncbi.nlm.nih.gov/pubmed/23847530", "http://www.ncbi.nlm.nih.gov/pubmed/22110351", "http://www.ncbi.nlm.nih.gov/pubmed/21694458", "http://www.ncbi.nlm.nih.gov/pubmed/22292124", "http://www.ncbi.nlm.nih.gov/pubmed/23254906", "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "http://www.ncbi.nlm.nih.gov/pubmed/22288451", "http://www.ncbi.nlm.nih.gov/pubmed/21897718", "http://www.ncbi.nlm.nih.gov/pubmed/22134132", "http://www.ncbi.nlm.nih.gov/pubmed/22672770", "http://www.ncbi.nlm.nih.gov/pubmed/23416764", "http://www.ncbi.nlm.nih.gov/pubmed/23735288", "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "http://www.ncbi.nlm.nih.gov/pubmed/23568994", "http://www.ncbi.nlm.nih.gov/pubmed/23663286", "http://www.ncbi.nlm.nih.gov/pubmed/20375655", "http://www.ncbi.nlm.nih.gov/pubmed/21614635", "http://www.ncbi.nlm.nih.gov/pubmed/24119446", "http://www.ncbi.nlm.nih.gov/pubmed/24399967" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "Drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "Solanezumab" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "Intervention #13258 (Drug:Solanezumab)" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2935150", "o": "http://linkedlifedata.com/resource/umls/id/C0003250" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469068", "o": "solanezumab" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17949023", "o": "Antibodies, Monoclonal [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0024758", "o": "Antibodies, Monoclonal" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7654540", "o": "Monoclonal Antibody" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A4346004", "o": "monoclonal antibodies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7572230", "o": "Monoclonal Antibodies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10786467", "o": "MoAB" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2935150", "o": "http://linkedlifedata.com/resource/umls/label/A18469068" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1307845", "o": "MAb" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0319457", "o": "monoclonal antibody" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18469068", "o": "C550616" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18469068", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2935151", "o": "http://linkedlifedata.com/resource/umls/id/C2935150" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18472154", "o": "LY-2062430" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18456783", "o": "LY 2062430" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18465965", "o": "LY2062430" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00637130", "o": "http://data.linkedct.org/resource/intervention/13258" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00637130", "o": "Trial NCT00637130" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/13258", "o": "13258" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0003250", "o": "http://linkedlifedata.com/resource/umls/id/C2935150" } ], "ideal_answer": [ "Solanezumab is a monoclonal anti-amyloid beta peptide (A\u03b2) antibody. It has been tested for treatment of Alzheimer's disease patients.", "Solanezumab, a humanized anti-A\u03b2 monoclonal antibody directed against the midregion of the A\u03b2 peptide, was shown to neutralize soluble A\u03b2 species." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ], "type": "summary", "id": "52fc94ae2059c6d71c000073", "snippets": [ { "offsetInBeginSection": 1156, "offsetInEndSection": 1456, "text": "Anti-amyloid treatment in asymptomatic AD (A4) is a prevention trial aimed at treating older individuals with normal cognition but at risk of developing AD dementia on the basis of having biomarker evidence of amyloid (preclinical AD). They selected solanezumab for the anti-amyloid treatment for A4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101429", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1056, "text": "Passive immunotherapy with monoclonal antibodies (mAbs) against A\u03b2 is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23663286", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 389, "text": "solanezumab, targeting monomeric A\u03b2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582316", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 387, "text": "Immunotherapeutic agents have been developed to remove the neurotoxic amyloid \u03b242 protein and prevent the hypothesized amyloid \u03b242-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 891, "text": "A\u03b2 removal and improved cognitive function in animal models of AD. Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23568994", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 156, "text": "solanezumab, an anti-\u03b2-amyloid (A\u03b2) antibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22672770", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1081, "text": "Anti-A\u03b2 monoclonal antibodies (bapineuzumab and solanezumab) are now being developed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "endSection": "abstract" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1571, "text": "Solanezumab, a humanized anti-A\u03b2 monoclonal antibody directed against the midregion of the A\u03b2 peptide, was shown to neutralize soluble A\u03b2 species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Solanezumab (LY2062430) is a humanized monoclonal antibody that binds to the central region of \u03b2-amyloid, a peptide believed to play a key role in the pathogenesis of Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22288451", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 176, "text": "Solanezumab is a humanized anti-amyloid \u03b2 monoclonal antibody being developed as a passive immunization treatment to slow the progression of Alzheimer disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134132", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 567, "text": "This situation was encountered in the development of LY2062430, a therapeutic mid-domain monoclonal anti-amyloid beta peptide (A\u03b2) antibody undergoing clinical trials for the treatment of Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21868184", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 250, "text": "Solanezumab is a monoclonal antibody that binds to \u03b2-amyloid (A\u03b2), a protein that plays a key role in the pathogenesis of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504387", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 912, "text": "Solanezumab can neutralize soluble A\u03b2 peptides,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504387", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 260, "text": "LY2062430 (solanezumab) is a humanized monoclonal antibody being studied as a putative disease-modifying treatment of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20375655", "endSection": "abstract" } ] }, { "body": "What are the major clinical Villefranche criteria for classic Ehlers-Danlos syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22696272" ], "ideal_answer": [ "The major clinical Villefranche criteria for classic Ehlers-Danlos syndrome are skin hyperextensibility, dystrophic scarring, and joint hypermobility." ], "exact_answer": [ [ "skin hyperextensibility" ], [ "dystrophic scarring" ], [ "joint hypermobility" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13359" ], "type": "list", "id": "54e1252fae9738404b000003", "snippets": [ { "offsetInBeginSection": 790, "offsetInEndSection": 995, "text": "All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696272", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 994, "text": "All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696272", "endSection": "abstract" } ] }, { "body": "What is the treatment of neuropathic pain in children?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22401313", "http://www.ncbi.nlm.nih.gov/pubmed/22147611", "http://www.ncbi.nlm.nih.gov/pubmed/18363625", "http://www.ncbi.nlm.nih.gov/pubmed/7561230", "http://www.ncbi.nlm.nih.gov/pubmed/15265351", "http://www.ncbi.nlm.nih.gov/pubmed/22735246", "http://www.ncbi.nlm.nih.gov/pubmed/18820538", "http://www.ncbi.nlm.nih.gov/pubmed/12712053", "http://www.ncbi.nlm.nih.gov/pubmed/21332246", "http://www.ncbi.nlm.nih.gov/pubmed/11902308" ], "ideal_answer": [ "It is unclear if any treatment is registered for pediatric use. The reported treatments are:\nOxcarbazepine \nOpioids alone, in rotations or with Analgesics (e.g. Ketamine and Lidocaine infusion)\nOpioids and Benzodiazepines\nPregabalin - is one of the first drugs registered for the treatment of neuropathic pain. It is unclear if Pregabalin is registered for the treatment of neuropathic pain in children specifically but it is being used in practice.\nTricyclic Antidepressants\nLidocaine 5% patches for chronic localized neuropathic pain" ], "exact_answer": [ [ "Oxcarbazepine" ], [ "Opioids alone, in rotations or with Analgesics (e.g. Ketamine and Lidocaine infusion)" ], [ "Opioids and Benzodiazepines - for terminal care" ], [ "Pregabalin" ], [ "Tricyclic Antidepressants" ], [ "Lidocaine 5% patches for chronic localized neuropathic pain" ], [ "Ketamine" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010146", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.disease-ontology.org/api/metadata/DOID:0060164" ], "type": "list", "id": "515da6e2298dcd4e51000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Oxcarbazepine, a metabolite of carbamazepine, is used as an antiepileptic, analgesic for neuropathic pain and in the treatment of affective disorders. It has been approved by the Food and Drug Administration for partial seizures in adults as both adjunctive and monotherapy, and as adjunctive therapy in children aged from 2 to 16 years", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735246", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "For difficult to treat neuropathic pain from cancer, adjuvant analgesics are often used with opioids", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22401313", "endSection": "sections.0" }, { "offsetInBeginSection": 448, "offsetInEndSection": 593, "text": "Ketamine and lidocaine can be safely infused together with concomitant opioids for the treatment of refractory neuropathic pain caused by cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22401313", "endSection": "sections.0" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1417, "text": "Patient-controlled analgesia with morphine as continuous subcutaneous or intravenous infusions and the possibility of a bolus injection is suited for children aged 6 years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147611", "endSection": "sections.0" }, { "offsetInBeginSection": 1773, "offsetInEndSection": 1881, "text": "In neuropathic pain or phantom pain coanalgetics should be used to effectively treat pain in young patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147611", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 236, "text": "Pregabalin is one of the first drugs registered for the treatment of neuropathic pain. It is also indicated as adjuvant therapy in the treatment of epilepsy and for generalized anxiety disorder. Pregabalin is a GABA analogue", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21332246", "endSection": "sections.0" }, { "offsetInBeginSection": 694, "offsetInEndSection": 1166, "text": "Treatment was typically initiated with a tricyclic antidepressant, and 5 of the 6 girls noted improvement in their symptoms, including 2 who had marked improvement, and another 3 with substantial improvement who were able to discontinue therapy without a recurrence. CONCLUSIONS: Vulvodynia does occur among young girls and, when treated as a neuropathic pain disorder, was found to dramatically improve or remit in the majority of those treated in this small case series.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18820538", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "We describe a case series of five adolescents who were managed with lidocaine 5% patches for chronic localized neuropathic pain from a variety of causes with minimal adverse effects. Treatment was effective in four of five patients with only one patient complaining of minimal pain relief", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18363625", "endSection": "sections.0" }, { "offsetInBeginSection": 317, "offsetInEndSection": 1022, "text": "Twenty-two children or 14% of children on opioid therapy underwent 30 opioid rotations. Mucositis was the cause of pain in 19 (70%) children, bone pain in 3 (11%) children, and postoperative, visceral, or neuropathic pain in the remainder. The opioid was rotated either for excessive side effects with adequate analgesia (70%), excessive side effects with inadequate analgesia (16.7%), or tolerance (6.7%). Five (23%) children required two rotations, 3 during the same admission. The favored rotations were morphine to fentanyl in 20 (67%) children and fentanyl to hydromorphone in 6 (20%). Adverse opioid effects were resolved in 90% of cases, all failures occurred when morphine was rotated to fentanyl.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265351", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 268, "text": "To test the hypothesis that children with terminal cancer and neuropathic pain require rapid increases of opioids and benzodiazepines immediately before death, we compared drug usage in the last 72 hours of life in children with and without neuropathic pain", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12712053", "endSection": "sections.0" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1394, "text": "Dying children with cancer and neuropathic pain have higher baseline requirements of morphine and benzodiazepines and require rapid increases of both drugs in the last 72 hours of life than dying children without neuropathic pain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12712053", "endSection": "sections.0" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1580, "text": "ketamine treatment may be effective in children with severe neuropathic pain not responsive to other analgesics. This patient also demonstrates the feasibility of long-term ketamine treatment in pediatric oncology and that such treatment can be administered in a home care setting.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11902308", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 734, "text": "Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this formulation have been limited to pharmacokinetic studies in normal volunteers, trials in depressed patients, and analyses of electroencephalogram (EEG) activation. We retrospectively reviewed our experience using intravenous (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate medications by the oral route, received IV amitriptyline for a variety of indications, including neuropathic pain, depression, sleep disturbance, and as an adjuvant agent for opioid analgesia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7561230", "endSection": "sections.0" } ] }, { "body": "Which phenomenon is known as the \"calcium paradox\" in the isolated perfused heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16901476", "http://www.ncbi.nlm.nih.gov/pubmed/6626051", "http://www.ncbi.nlm.nih.gov/pubmed/4058248", "http://www.ncbi.nlm.nih.gov/pubmed/1031954", "http://www.ncbi.nlm.nih.gov/pubmed/2720439", "http://www.ncbi.nlm.nih.gov/pubmed/6823106", "http://www.ncbi.nlm.nih.gov/pubmed/24289081", "http://www.ncbi.nlm.nih.gov/pubmed/23284963", "http://www.ncbi.nlm.nih.gov/pubmed/3117031" ], "ideal_answer": [ "When hearts are reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity is observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the \"calcium paradox\". This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores. The Ca(2+) paradox represents a good model to study Ca(2+) overload injury in ischemic heart diseases. The Ca(2+) paradox can be elicited by perfusing isolated hearts with Ca(2+)-free media for 3 min or 5 min followed by 30 min of Ca(2+) repletion. A possible mechanism for the 'calcium paradox' is that exposure to a calcium-free medium removes extracellular calcium rendering the sarcolemma more permeable to calcium. On calcium repletion, cell injury is triggered by calcium influx. Cardiac dysfunction due to Ca2+ -paradox may be associated with apoptosis.", "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. ", "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the calcium paradox . Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. ", "\"Calcium paradox\" as a term describes the deleterious effects conferred to a heart perfused with a calcium-free solution followed by repletion, including loss of mechanical activity and sarcomere disruption.Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002118", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010477", "http://www.biosemantics.org/jochem#4277675" ], "type": "summary", "id": "54fc3cf410565e080c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "\"Calcium paradox\" as a term describes the deleterious effects conferred to a heart perfused with a calcium-free solution followed by repletion, including loss of mechanical activity and sarcomere disruption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289081", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 487, "text": "Calcium paradox was found to markedly activate members of the MAPKs (p43-ERK, JNKs, p38-MAPK). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289081", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1352, "text": "To our knowledge, this is the first time that the calcium paradox has been shown to induce apoptosis in amphibians, with p38-MAPK and calpain playing significant roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The Ca(2+) paradox represents a good model to study Ca(2+) overload injury in ischemic heart diseases. We and others have demonstrated that contracture and calpain are involved in the Ca(2+) paradox-induced injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23284963", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 421, "text": "The Ca(2+) paradox was elicited by perfusing isolated rat hearts with Ca(2+)-free KH media for 3 min or 5 min followed by 30 min of Ca(2+) repletion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23284963", "endSection": "abstract" }, { "offsetInBeginSection": 1749, "offsetInEndSection": 1925, "text": "These results provide evidence suggesting that contracture is the main cause for contractile dysfunction, while activation of calpain mediates cell death in the Ca(2+) paradox.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23284963", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 353, "text": "The Ca2+ -paradox is an important phenomenon to study cell injury induced by Ca2+ -overload in myocardium. Although intracellular Ca2+ -overload acts as a trigger and modulator of cell death due to apoptosis under various pathophysiological conditions, the presence of apoptosis in hearts subjected to Ca2+ -paradox has not been demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16901476", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 742, "text": "Ca2+ -paradox was induced by perfusing the isolated rat heart with Ca2+ -free medium for 5 min followed by reperfusion with Ca2+ -containing medium for 30 min.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16901476", "endSection": "abstract" }, { "offsetInBeginSection": 2030, "offsetInEndSection": 2129, "text": "This study suggests that cardiac dysfunction due to Ca2+ -paradox may be associated with apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16901476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 581, "text": "Normothermic 3 min lasting perfusion of the isolated rat heart by Krebs--Henseleit solution in which Ca2+ was replaced by EDTA and subsequent perfusion with a Ca2+ containing medium induced structural and metabolic changes demonstrated electron microscopically and histochemically. In contrast to the ischemic reperfusion damage, in calcium paradox, the histochemically studied enzymes alpha-glucan-phosphorylase, lactate dehydrogenase, succinic dehydrogenase, beta-hydroxybutyric dehydrogenase, and ATPases were better preserved in the subendocardial region of the left ventricle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2720439", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 1199, "text": "On the other hand, myocytes in the subepicardial region and in the midmyocardium were markedly damaged and all characteristic signs of calcium paradox were present, including hypercontraction bands with myofilament fusion, extrusion and accumulation of edematous mitochondria with occurrence of electron dense material in mitochondrial cristae, ruptures of the sarcolemma in all its layers, separation of intercalated discs, etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2720439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 492, "text": "Intracellular Ca2+-overload in the myocardium can be induced not only after readmission of Ca2+-containing fluid to rat hearts previously perfused with a Ca2+-free buffer, a phenomenon called \"the calcium paradox\", but also during administration of a Ca2+-ionophore to cardiac tissue. In rat hearts, the myocardial damage induced by the Ca2+ paradox was more pronounced than that after administration of the Ca2+-ionophore A23187, as indicated by the amount of lactate dehydrogenase released.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3117031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 364, "text": "When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the \"calcium paradox\". Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4058248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "Injury is sustained by isolated hearts on repletion with calcium after a short period of perfusion with calcium-free medium at 37 degrees. A possible mechanism for the 'calcium paradox' is that exposure to a calcium-fre medium removes extracellular calcium rendering the sarcolemma more permeable to calcium. On calcium repletion, cell injury is triggered by calcium influx.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6626051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6823106", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1075, "text": "It is concluded that there is no calcium paradox in canine kidney under these conditions and it is suggested that the Ca2+ paradox may be characteristics only of muscle tissue that can undergo Ca2+-dependent contraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6823106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1031954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6823106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6823106", "endSection": "abstract" } ] }, { "body": "Is there a crystal structure of the full-length of the flaviviridae NS5(Methyltransferase - RNA depended RNA Polymerase) ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22365326", "http://www.ncbi.nlm.nih.gov/pubmed/19710254", "http://www.ncbi.nlm.nih.gov/pubmed/23355615", "http://www.ncbi.nlm.nih.gov/pubmed/22757685", "http://www.ncbi.nlm.nih.gov/pubmed/17287213", "http://www.ncbi.nlm.nih.gov/pubmed/23950717" ], "ideal_answer": [ "Yes, there is the crystal Structure of the full-length Japanese encephalitis virus (Flaviviridae) NS5 - PDB:4K6M" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003460", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018178", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006127" ], "type": "yesno", "id": "532aad53d6d3ac6a34000010", "snippets": [ { "offsetInBeginSection": 3, "offsetInEndSection": 456, "text": " flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal \u2248 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23950717", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 980, "text": "(DENV) nonstructural protein 5 (NS5) is composed of two globular domains separated by a 10-residue linker. The N-terminal domain participates in the synthesis of a mRNA cap 1 structure ((7Me)GpppA(2'OMe)) at the 5' end of the viral genome and possesses guanylyltransferase, guanine-N7-methyltransferase, and nucleoside-2'O-methyltransferase activities. The C-terminal domain is an RNA-dependent RNA polymerase responsible for viral RNA synthesis. Although crystal structures of the two isolated domains have been obtained, there are no structural data for full-length NS5. It is also unclear whether the two NS5 domains interact with each other to form a stable structure in which the relative orientation of the two domains is fixed. To investigate the structure and dynamics of DENV type 3 NS5 in solution, we conducted small-angle X-ray scattering experiments with the full-length protein. NS5 was found to be monomeric and well-folded under the conditions tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22757685", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 1391, "text": "West Nile virus (WNV) NS5 protein contains a methyltransferase (MTase) domain involved in RNA capping and an RNA-dependent RNA polymerase (RdRp) domain essential for virus replication. Crystal structures of individual WNV MTase and RdRp domains have been solved; however, the structure of full-length NS5 has not been determined. To gain more insight into the structure of NS5 and interactions between the MTase and RdRp domains, we generated a panel of seven monoclonal antibodies (mAbs) to the NS5 protein of WNV (Kunjin strain) and mapped their binding sites using a series of truncated NS5 proteins and synthetic peptides. Binding sites of four mAbs (5D4, 4B6, 5C11 and 6A10) were mapped to residues 354-389 in the fingers subdomain of the RdRp. This is consistent with the ability of these mAbs to inhibit RdRp activity in vitro and suggests that this region represents a potential target for RdRp inhibitors. Using a series of synthetic peptides, we also identified a linear epitope (bound by mAb 5H1) that mapped to a 13 aa stretch surrounding residues 47 and 49 in the MTase domain, a region predicted to interact with the palm subdomain of the RdRp. The failure of one mAb (7G6) to bind both N- and C-terminally truncated NS5 recombinants indicates that the antibody recognizes a conformational epitope that requires the presence of residues in both the MTase and RdRp domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19710254", "endSection": "abstract" } ] }, { "body": "How do Hsp70 and Hsp110 affect mRNA stability?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10358092" ], "ideal_answer": [ "Hsp70 and Hsp110 act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation." ], "type": "summary", "id": "56cafb1b5795f9a73e00002f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10358092", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 201, "text": "Hsp/Hsc70 and Hsp110 proteins preferentially bound AU-rich RNA in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10358092", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1268, "text": "certain heat shock proteins may act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10358092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10358092", "endSection": "title" } ] }, { "body": "What is Prudent Diet?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23741179", "http://www.ncbi.nlm.nih.gov/pubmed/17076904", "http://www.ncbi.nlm.nih.gov/pubmed/20624672", "http://www.ncbi.nlm.nih.gov/pubmed/2173390", "http://www.ncbi.nlm.nih.gov/pubmed/22034645", "http://www.ncbi.nlm.nih.gov/pubmed/23953031", "http://www.ncbi.nlm.nih.gov/pubmed/207959", "http://www.ncbi.nlm.nih.gov/pubmed/6622440", "http://www.ncbi.nlm.nih.gov/pubmed/23639938", "http://www.ncbi.nlm.nih.gov/pubmed/11493127", "http://www.ncbi.nlm.nih.gov/pubmed/16580586", "http://www.ncbi.nlm.nih.gov/pubmed/22835136", "http://www.ncbi.nlm.nih.gov/pubmed/21676220", "http://www.ncbi.nlm.nih.gov/pubmed/15853117", "http://www.ncbi.nlm.nih.gov/pubmed/23885043", "http://www.ncbi.nlm.nih.gov/pubmed/23524862", "http://www.ncbi.nlm.nih.gov/pubmed/23530637", "http://www.ncbi.nlm.nih.gov/pubmed/1511475", "http://www.ncbi.nlm.nih.gov/pubmed/18796495", "http://www.ncbi.nlm.nih.gov/pubmed/4072955", "http://www.ncbi.nlm.nih.gov/pubmed/7870637", "http://www.ncbi.nlm.nih.gov/pubmed/22914994", "http://www.ncbi.nlm.nih.gov/pubmed/23933622", "http://www.ncbi.nlm.nih.gov/pubmed/3819235", "http://www.ncbi.nlm.nih.gov/pubmed/216895", "http://www.ncbi.nlm.nih.gov/pubmed/22717188", "http://www.ncbi.nlm.nih.gov/pubmed/1852180", "http://www.ncbi.nlm.nih.gov/pubmed/422845", "http://www.ncbi.nlm.nih.gov/pubmed/23398686", "http://www.ncbi.nlm.nih.gov/pubmed/15539255", "http://www.ncbi.nlm.nih.gov/pubmed/3886611" ], "ideal_answer": [ "The Prudent dietary pattern is characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products, legumes, fish, poultry. Generally recommendations are to use saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake \u2265 25 g/day in women and \u2265 35 grams per day in men." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004035", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005526", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005510", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004032" ], "type": "summary", "id": "533175add6d3ac6a3400003c", "snippets": [ { "offsetInBeginSection": 518, "offsetInEndSection": 704, "text": "Long-term diet was assessed by using FFQs every 4 y since 1986. Prudent (high in vegetables) and Western (high in meats) patterns were identified by using a principal component analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23885043", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1076, "text": "The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398686", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 765, "text": "aerobic exercise combined with diet recommendations (saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake \u2265 25 g/day in women and \u2265 35 grams per day in men", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21676220", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1039, "text": " a prudent pattern (high in fish, peas, honey, nuts, juice, dry fruits, vegetable oil, liver and organic meat, and coconuts and low in hydrogenated fat and non-leafy vegetables)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624672", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 942, "text": " The prudent pattern was characterized by higher intakes of fruits, vegetables, legumes, fish, poultry, and whole grains, while the Western pattern was characterized by higher intakes of red and processed meats, sweets and desserts, french fries, and refined grains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11493127", "endSection": "abstract" } ] }, { "body": "What is the role of necroptosis in cancer therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23875666", "http://www.ncbi.nlm.nih.gov/pubmed/23301705", "http://www.ncbi.nlm.nih.gov/pubmed/23625539", "http://www.ncbi.nlm.nih.gov/pubmed/23729362" ], "ideal_answer": [ "Necroptosis, a novel form of programmed cell death (PCD), is caspase independent but RIPK and RIPK3 dependent. The apoptotic, autophagic and necroptotic pathways of PCD were shown to be interconnected, with molecules such as FLIP acting as a bridge between them. Therefore, simultaneous activation of the three PCD pathways would make cancer therapy more effective, whereas induction of necroptosis could be an alternative, in cases where apoptosis-inducing cancer chemotherapy is not effective. For example, inhibition of GSK3B was found to bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to 5-FU treatment." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070266", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060553", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060544" ], "type": "summary", "id": "53175f0bb166e2b80600000c", "snippets": [ { "offsetInBeginSection": 514, "offsetInEndSection": 707, "text": "Previous evidences suggest that necroptosis has significant effects in regulating various physiological processes and disease, such as ischemic brain injury, immune system disorders and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23875666", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 513, "text": "Its signaling pathways have something in common with apoptosis, although the molecular mechanisms of necroptosis need to be further elucidated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23875666", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 369, "text": "Necroptosis, a novel form of programmed cell death, is caspase independent but RIPK and RIPK3 dependent. Moreover, it is suggested that necroptosis can be specifically inhibited by small molecular inhibitors such as necrostatin-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23875666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Inhibition of GSK3B bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to chemotherapy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729362", "endSection": "title" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1523, "text": "Cell death of 5-fluorouracil (5FU)-treated p53-null GSK3B-silenced colon carcinoma cells occurred via PARP1-dependent and AIF-mediated but RIP1-independent necroptosis. In vivo studies showed that drug-resistant xenograft tumor mass was significantly reduced only when 5FU was given after GSK3B inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729362", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 833, "text": "Inducing programmed cell death (PCD) is a promising method to prevent or inhibit the progression of tumor cells. Intricate cross talk among various programmed cell death pathways including cell death by apoptosis, necroptosis or autophagy plays a critical role in the regulation of PCD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625539", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1265, "text": "This review article focuses on targeting FLIP (Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein) signaling as a bridge between various PCD processes as an effective approach for cancer management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23301705", "endSection": "title" }, { "offsetInBeginSection": 759, "offsetInEndSection": 944, "text": "Upon introduction of molecular pathways governing autophagy and necrosis (also called necroptosis or programmed necrosis), we focus on the interconnected character of cell death signals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23301705", "endSection": "abstract" } ] }, { "body": "Can venlafaxine block NET and SERT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10490914", "http://www.ncbi.nlm.nih.gov/pubmed/9252010", "http://www.ncbi.nlm.nih.gov/pubmed/12784104", "http://www.ncbi.nlm.nih.gov/pubmed/16140280", "http://www.ncbi.nlm.nih.gov/pubmed/23090625", "http://www.ncbi.nlm.nih.gov/pubmed/15989562", "http://www.ncbi.nlm.nih.gov/pubmed/18923402", "http://www.ncbi.nlm.nih.gov/pubmed/18418363", "http://www.ncbi.nlm.nih.gov/pubmed/18538356", "http://www.ncbi.nlm.nih.gov/pubmed/11454918", "http://www.ncbi.nlm.nih.gov/pubmed/10884561", "http://www.ncbi.nlm.nih.gov/pubmed/11524036", "http://www.ncbi.nlm.nih.gov/pubmed/9400006" ], "ideal_answer": [ "Yes, venlafaxine inhibits both the NET and SERT." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4277061" ], "type": "yesno", "id": "56cf32e23975bb303a000006", "snippets": [ { "offsetInBeginSection": 1148, "offsetInEndSection": 1395, "text": "Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced antidepressant-like effects on behavior without altering NET or SERT expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18923402", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 124, "text": "Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140280", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1343, "text": "Chronic venlafaxine treatment affected SERT and NET binding differently from paroxetine or desipramine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter (NET) antagonists", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18418363", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 453, "text": "Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18418363", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1394, "text": "Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced antidepressant-like effects on behavior without altering NET or SERT expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18923402", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1176, "text": "We then performed the first reported investigation of epistasis between the SERT gene and norepinephrine transporter gene (SLC6A2, alias NET) in AN, as an earlier study suggested that atypical AN responds to the dual serotonin-norepinephrine reuptake inhibitor venlafaxine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12784104", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1159, "text": "Of particular interest were the findings that paroxetine, generally thought of as a selective SERT antagonist, possesses moderately high affinity for the NET and that venlafaxine, which has been described as a "dual uptake inhibitor", possesses weak affinity for the NET", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9400006", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1181, "text": "The ratios of measured occupancy ED(50) values (doses at which 50% occupancy occurs) among SERT, NET and DAT sites for duloxetine, venlafaxine, nomifensine, indatraline, DOV 21,947 and DOV 216,303 were consistent with the ratios of the in vitro affinities between these target binding sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18538356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "SERT and NET occupancy by venlafaxine and milnacipran in nonhuman primates: a PET study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090625", "endSection": "title" }, { "offsetInBeginSection": 390, "offsetInEndSection": 583, "text": "In this study in nonhuman primates, we aimed to investigate the relationship between SERT and NET affinity by measuring the in vivo occupancy at both transporters of venlafaxine and milnacipran", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090625", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 665, "text": "We hypothesized that venlafaxine would affect monoamine transporters dose-dependently, with low doses causing selective reduction of SERT binding sites and higher doses reducing both SERT and NET binding sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140280", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1684, "text": "Comparative studies with clinically used antidepressants showed that venlafaxine possessed a profile similar to S33005 but was less potent. Clomipramine likewise interacted with SERTs and NETs but also with several other receptors types, while citalopram and reboxetine were preferential ligands of SERTs and NETs, respectively. In conclusion, S33005 interacts potently with SERTs and, less markedly, with NETs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11454918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT. Serotonergic effects occur with lower doses, whereas both serotonergic and noradrenergic effects occur with higher doses of venlafaxine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140280", "endSection": "abstract" }, { "offsetInBeginSection": 2257, "offsetInEndSection": 2685, "text": "Taken together, the results from this study indicate that the low dose of venlafaxine blocked selectively the reuptake of 5-HT, whereas the high dose blocked the reuptake of both 5-HT and NE. Moreover, an enhancement of serotonergic neurotransmission by venlafaxine was only achieved under conditions whereby the desensitization of the terminal 5-HT(1B) autoreceptor is appended to that of the somatodendritic 5-HT(1A) receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10884561", "endSection": "abstract" } ] }, { "body": "Is Rheumatoid Arthritis more common in men or women?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21340496", "http://www.ncbi.nlm.nih.gov/pubmed/22853635", "http://www.ncbi.nlm.nih.gov/pubmed/19158113", "http://www.ncbi.nlm.nih.gov/pubmed/20889597", "http://www.ncbi.nlm.nih.gov/pubmed/18759162", "http://www.ncbi.nlm.nih.gov/pubmed/16418123", "http://www.ncbi.nlm.nih.gov/pubmed/17965425", "http://www.ncbi.nlm.nih.gov/pubmed/15083883", "http://www.ncbi.nlm.nih.gov/pubmed/1563036", "http://www.ncbi.nlm.nih.gov/pubmed/12723987", "http://www.ncbi.nlm.nih.gov/pubmed/20810033", "http://www.ncbi.nlm.nih.gov/pubmed/23217568" ], "ideal_answer": [ "Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome." ], "exact_answer": [ "Women" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001171", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015535", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013167", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012217" ], "type": "factoid", "id": "5118dd1305c10fae75000001", "snippets": [ { "offsetInBeginSection": 591, "offsetInEndSection": 678, "text": "Our results show a high prevalence of RA in LAC women with a ratio of 5.2 women per man", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23217568", "endSection": "sections.0" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1394, "text": "RA in LAC women is not only more common but presents with some clinical characteristics that differ from RA presentation in men. Some of those characteristics could explain the high rates of disability and worse prognosis observed in women with RA in LAC", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23217568", "endSection": "sections.0" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1062, "text": "Intense anti-CCP2 reaction was 19.8-fold higher in females vs. males,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21340496", "endSection": "sections.0" }, { "offsetInBeginSection": 911, "offsetInEndSection": 944, "text": " men (n = 67) and women (n = 225)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20889597", "endSection": "sections.0" }, { "offsetInBeginSection": 1808, "offsetInEndSection": 1943, "text": " Responses to treatment over time were better among men in this prebiologic era; women had worse progression despite similar treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20889597", "endSection": "sections.0" }, { "offsetInBeginSection": 1550, "offsetInEndSection": 1629, "text": "BMI appears to be associated with RA disease activity in women, but not in men.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810033", "endSection": "sections.0" }, { "offsetInBeginSection": 729, "offsetInEndSection": 785, "text": "A total of 5,161 RA patients (4,082 women and 1,079 men)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810033", "endSection": "sections.0" }, { "offsetInBeginSection": 561, "offsetInEndSection": 744, "text": "In women the DAS28 was significantly higher than in men due to higher scores for general health and tender joints. Likewise, HAQ and VAS pain were rated significantly higher in women.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19158113", "endSection": "sections.0" }, { "offsetInBeginSection": 263, "offsetInEndSection": 285, "text": "432 females, 125 males", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759162", "endSection": "sections.0" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1017, "text": "ESR significantly increased with age, independent of other variables of disease activity. This increase was more pronounced in male than in female patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17965425", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1563036", "endSection": "sections.0" }, { "offsetInBeginSection": 688, "offsetInEndSection": 830, "text": "The female to male ratio was 2.5:1 and the mean age at diagnosis was 49.4 +/- 14.9 years for women and 55.3 +/-15.6 years for men (P < 0.0003)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15083883", "endSection": "sections.0" }, { "offsetInBeginSection": 453, "offsetInEndSection": 514, "text": "in 244 female and 91 male patients with rheumatoid arthritis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16418123", "endSection": "sections.0" } ] }, { "body": "What is FINDbase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21113021", "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "http://www.ncbi.nlm.nih.gov/pubmed/22659238", "http://www.ncbi.nlm.nih.gov/pubmed/24234438" ], "ideal_answer": [ "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Database access is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.", "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ], "type": "summary", "id": "56c234a4ef6e394741000059", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1502, "text": "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Databaseaccess is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24234438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 558, "text": "We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "FINDbase: a worldwide database for genetic variation allele frequencies updated.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21113021", "endSection": "title" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1502, "text": "FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 344, "text": "We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24234438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 345, "text": "We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659238", "endSection": "abstract" } ] }, { "body": "Can vitamin B1 deficiency cause encephalopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9279523", "http://www.ncbi.nlm.nih.gov/pubmed/20943242", "http://www.ncbi.nlm.nih.gov/pubmed/23042832", "http://www.ncbi.nlm.nih.gov/pubmed/24620429", "http://www.ncbi.nlm.nih.gov/pubmed/24379094", "http://www.ncbi.nlm.nih.gov/pubmed/24973622", "http://www.ncbi.nlm.nih.gov/pubmed/23935638", "http://www.ncbi.nlm.nih.gov/pubmed/23090806", "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "http://www.ncbi.nlm.nih.gov/pubmed/14644703", "http://www.ncbi.nlm.nih.gov/pubmed/22703872", "http://www.ncbi.nlm.nih.gov/pubmed/24117525", "http://www.ncbi.nlm.nih.gov/pubmed/25276464", "http://www.ncbi.nlm.nih.gov/pubmed/7695937", "http://www.ncbi.nlm.nih.gov/pubmed/23278769", "http://www.ncbi.nlm.nih.gov/pubmed/23715222", "http://www.ncbi.nlm.nih.gov/pubmed/16254404", "http://www.ncbi.nlm.nih.gov/pubmed/25050351", "http://www.ncbi.nlm.nih.gov/pubmed/21217196", "http://www.ncbi.nlm.nih.gov/pubmed/24701066", "http://www.ncbi.nlm.nih.gov/pubmed/11304071", "http://www.ncbi.nlm.nih.gov/pubmed/2361826" ], "ideal_answer": [ "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. It is commonly associated with heavy alcohol consumption. Other clinical associations are with hyperemesis gravidarum (HG), starvation, and prolonged intravenous feeding.", "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia" ], "exact_answer": "yes", "type": "yesno", "id": "572211540fd6f91b68000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Wernicke's encephalopathy (WE) is a potentially reversible yet serious neurological manifestation caused by vitamin B1(thiamine) deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24701066", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 81, "text": "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 876, "text": "Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9279523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Wernicke's encephalopathy (WE) is an acute neurological disease resulting from thiamine (vitamin B1) deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24620429", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 525, "text": "Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11304071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Wernicke's encephalopathy is an acute neuropsychiatric disorder, due to thiamine (vitamin B1) deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25276464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20943242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24117525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke's encephalopathy (WE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24973622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Wernicke's encephalopathy is caused by thiamin deficiency and can be recognized by severe neurological symptoms that are occasionally accompanied by systemic signs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7695937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "INTRODUCTION: Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20943242", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 518, "text": "OBSERVATION: We report a case of encephalopathy due to dual vitamin deficiency of both thiamine (vitamin\u00a0B1) and niacin (vitamin\u00a0PP) in an 80-year-old women, hospitalized for severe sepsis caused by aspiration pneumonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22703872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Acute Wernicke's encephalopathy (WE) is caused by profound vitamin B1 (thiamine) deficiency and commonly presents with the classic clinical triad of mental confusion, ataxia, and ophthalmoplegia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "[Wernicke\u00b4s encephalopathy and polyneuropathy associated with vitamin B complex deficiency after a bariatric surgery].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23715222", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "BACKGROUND: Thiamine deficiency in patients who abuse alcohol can cause Wernicke's encephalopathy (WE). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23278769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Wernicke encephalopathy--a debilitating acute or subacute neurological disorder-is caused by a deficiency in thiamine (vitamin B(1)). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23042832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Wernicke's encephalopathy is a serious neurological manifestation of vitamin B1 deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2361826", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 723, "text": "Both the thyrotoxicosis and a catabolic state due to the hyperemesis were thought to have induced a vitamin B1 deficiency, causing the Wernicke encephalopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9279523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090806", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 603, "text": "Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients. The causes of vitamin deficiency are reviewed with special attention to the inhibition of oral thiamine hydrochloride absorption in man caused by malnutrition present in alcoholic patients or by the direct effects of ethanol on intestinal transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11304071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Wernicke's encephalopathy is a serious neurologic disorder caused by vitamin-B1 or thiamine deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14644703", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 276, "text": "Wernicke's encephalopathy results from thiamine (vitamin B1) deficiency. Common causes include alcoholism and gastric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23935638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217196", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 353, "text": "Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11304071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20943242", "endSection": "abstract" } ] }, { "body": "Which methyl-CpG-binding protein when mutant becomes the hallmark for Rett syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18534925", "http://www.ncbi.nlm.nih.gov/pubmed/22138506", "http://www.ncbi.nlm.nih.gov/pubmed/22302819", "http://www.ncbi.nlm.nih.gov/pubmed/11180222" ], "ideal_answer": [ "Rett syndrome (RTT) was shown to be caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, with molecular studies identifying MECP2 mutations in up to 80% of classic RTT patients. MECP2 protein was found to assist in the transcriptional silencing process via DNA methylation. We therefore hypothesize that disruption of this gene alters the normal developmental expression of various other genes, some of which must account for the peculiar neurologic phenotype of RTT." ], "exact_answer": [ "Methyl-CpG-binding protein 2 (MECP2)" ], "concepts": [ "http://www.uniprot.org/uniprot/MECP2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032259", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004268", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015518", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051783", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008327", "http://www.disease-ontology.org/api/metadata/DOID:1206" ], "type": "factoid", "id": "534ebb59288f4dae47000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Rett syndrome (RTT) results from loss-of-function mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2) and is characterized by abnormal motor, respiratory and autonomic control, cognitive impairment, autistic-like behaviors and increased risk of seizures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22302819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Rett syndrome (RTT) is an autism spectrum disorder caused by mutation in the gene encoding methyl CpG binding protein 2 (MECP2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22138506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "Severely arrhythmic breathing is a hallmark of Rett syndrome (RTT) and profoundly affects quality of life for patients and their families. The last decade has seen the identification of the disease-causing gene, methyl-CpG-binding protein 2 (Mecp2) and the development of mouse models that phenocopy many aspects of the human syndrome, including breathing dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18534925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder that manifests in females, typically after the first year of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11180222", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 695, "text": "It was recently discovered that RTT is caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. MECP2 assists in the transcriptional silencing process via DNA methylation; we hypothesize that disruption of this gene alters the normal developmental expression of various other genes, some of which must account for the peculiar neurologic phenotype of RTT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11180222", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 927, "text": "Molecular studies have identified MECP2 mutations in up to 80% of classic RTT patients; mutation type has some effect on the phenotypic manifestation of RTT, but the pattern of X inactivation seems to determine phenotypic severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11180222", "endSection": "abstract" } ] }, { "body": "Are epigenetic modifications implicated in cardiovascular development and disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22773406", "http://www.ncbi.nlm.nih.gov/pubmed/22981780", "http://www.ncbi.nlm.nih.gov/pubmed/20603647", "http://www.ncbi.nlm.nih.gov/pubmed/21372004", "http://www.ncbi.nlm.nih.gov/pubmed/23448446", "http://www.ncbi.nlm.nih.gov/pubmed/22035349", "http://www.ncbi.nlm.nih.gov/pubmed/23261320", "http://www.ncbi.nlm.nih.gov/pubmed/19488075", "http://www.ncbi.nlm.nih.gov/pubmed/23640490", "http://www.ncbi.nlm.nih.gov/pubmed/21764886", "http://www.ncbi.nlm.nih.gov/pubmed/20881938", "http://www.ncbi.nlm.nih.gov/pubmed/22234702", "http://www.ncbi.nlm.nih.gov/pubmed/24183004", "http://www.ncbi.nlm.nih.gov/pubmed/22669047", "http://www.ncbi.nlm.nih.gov/pubmed/22621747" ], "ideal_answer": [ "Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD).Recent studies have greatly expanded our understanding of the regulation of cardiovascular development at the chromatin level, including the remodeling of chromatin and the modification of histones. Thus, understanding chromatin-level regulation will allow for a better appreciation of gene regulation as a whole and may set a fundamental basis for cardiovascular disease." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057890", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318" ], "type": "yesno", "id": "54f7291630767eb92e000002", "snippets": [ { "offsetInBeginSection": 1016, "offsetInEndSection": 1252, "text": "Gene expression regulation through the interplay of DNA methylation and histone modifications is well-established, although the knowledge about the function of epigenetic signatures in cardiovascular disease is still largely unexplored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981780", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1508, "text": "The study of epigenetic markers is, therefore, a very promising frontier of science which may aid in a deeper understanding of molecular mechanisms underlying the modulation of gene expression in the biomolecule pathways linked to cardiovascular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981780", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1291, "text": "This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodeling and histone modifications play key roles in the pathogenesis of cardiovascular disease through (re)programming of cardiovascular (stem) cells commitment, identity and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773406", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 918, "text": "Notably, multiple subunits of switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complexes have been identified as strong candidates underlying these defects because they physically and functionally interact with cardiogenic transcription factors critical to cardiac development, such as TBX5, GATA-4, and NKX2-5. While these studies indicate a critical role of SWI/SNF complexes in cardiac development and congenital heart disease, many exciting new discoveries have identified their critical role in the adult heart in both physiological and pathological conditions involving multiple cell types in the heart, including cardiomyocytes, vascular endothelial cells, pericytes, and neural crest cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183004", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1535, "text": "Recent studies have greatly expanded our understanding of the regulation of cardiovascular development at the chromatin level, including the remodeling of chromatin and the modification of histones. Chromatin-level regulation integrates multiple inputs and coordinates broad gene expression programs. Thus, understanding chromatin-level regulation will allow for a better appreciation of gene regulation as a whole and may set a fundamental basis for cardiovascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22035349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23640490", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 521, "text": "Epigenetic modifications, including DNA methylation, histone modification (acetylation, methylation and phosphorylation) and miRNA, are critical for regulating developmental events. However, aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD), neurodegenerative disease, obesity, metabolic disorder, bone and skeletal diseases and various cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448446", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1423, "text": "Cardiovascular disease pathways are now being approached from the epigenetic perspective, including those associated with atherosclerosis, angiogenesis, ischemia-reperfusion damage, and the cardiovascular response to hypoxia and shear stress, among many others. With increasing interest and expanding partnerships in the field, we can expect new insights to emerge from epigenetic perspectives of cardiovascular health.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261320", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 357, "text": "Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22669047", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 865, "text": "From varied study approaches directed either toward the general understanding of the key pathway regulatory genes, or sampling population cohorts for global and gene-specific changes, it has been possible to identify several epigenetic signatures of environmental exposure relevant to CVD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22669047", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1423, "text": "An understanding of chromatin remodelling in response to environmental stimuli conducive to CVD is emerging, with the promise of novel diagnostic and therapeutic candidates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22669047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 651, "text": "Consolidated knowledge is accumulating as to the role of epigenetic regulatory mechanisms in the physiology of vascular development and vascular tone as well as in the pathogenesis of cardiovascular disease. The modulation of gene expression through modification of the epigenome by structural changes of the chromatin architecture without alterations of the associated genomic DNA sequence is part of the cellular response to environmental changes. Such environmental conditions, which are finally being translated into adaptations of the cardiovascular system, also comprise pathological conditions such as atherosclerosis or myocardial infarction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22621747", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1187, "text": "Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease. Histone modifications lead to the modulation of the expression of genetic information through modification of DNA accessibility. In addition, RNA-based mechanisms (e.g., microRNAs and long non-coding RNAs) influence the development of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234702", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1289, "text": "We here outline the recent work pertaining to epigenetic changes in a cardiovascular disease setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234702", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 473, "text": "Epigenetics may represent one of the possible scientific explanations of the impact of such intrauterine risk factors for the subsequent development of cardiovascular disease (CVD) during adulthood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764886", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1272, "text": "Epigenetic mechanisms include DNA methylation, histone modification, and microRNA alterations, which collectively enable the cell to respond quickly to environmental changes. A number of CVD risk factors, such as nutrition, smoking, pollution, stress, and the circadian rhythm, have been associated with modification of epigenetic marks. Further examination of these mechanisms may lead to earlier prevention and novel therapy for CVD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20603647", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 934, "text": " Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234702", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 943, "text": "Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234702", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1265, "text": "Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20881938", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 942, "text": "Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Epigenetic mechanisms that underpin metabolic and cardiovascular diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19488075", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Epigenetic regulation of cardiovascular differentiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21372004", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Epigenetic control mechanisms play a key role in the regulation of embryonic development and tissue homeostasis and modulate cardiovascular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21372004", "endSection": "abstract" } ] }, { "body": "Which deiodinases are present in skeletal muscle?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19293265", "http://www.ncbi.nlm.nih.gov/pubmed/17986277", "http://www.ncbi.nlm.nih.gov/pubmed/23396445", "http://www.ncbi.nlm.nih.gov/pubmed/16127464" ], "ideal_answer": [ "Type 2 and Type 3 deiodinases are expressed in skeletal muscle and their expression is modulated by disease state and fasting." ], "exact_answer": [ [ "Type 2 deiodinase" ], [ "Tipe 3 deiodinase" ] ], "type": "list", "id": "517a8bef8ed59a060a000041", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 335, "text": "The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in systemic as well as local T3 production", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19293265", "endSection": "sections.0" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1435, "text": "Human skeletal muscle D2 mRNA expression is modulated by fasting and insulin, but not by hypothyroidism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19293265", "endSection": "sections.0" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1414, "text": "SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17986277", "endSection": "sections.0" }, { "offsetInBeginSection": 338, "offsetInEndSection": 558, "text": "Deiodinase activities were then assayed in cell sonicates. The ratio of T3 production in cell sonicates (catalytic efficiency) was multiplied by the tissue activities reported in human liver (D1) and skeletal muscle (D2)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16127464", "endSection": "sections.0" } ] }, { "body": "Which genes are involved in patient response to warfarin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23208322", "http://www.ncbi.nlm.nih.gov/pubmed/22321278", "http://www.ncbi.nlm.nih.gov/pubmed/22023024", "http://www.ncbi.nlm.nih.gov/pubmed/21651319", "http://www.ncbi.nlm.nih.gov/pubmed/17496169", "http://www.ncbi.nlm.nih.gov/pubmed/19348697", "http://www.ncbi.nlm.nih.gov/pubmed/18464049", "http://www.ncbi.nlm.nih.gov/pubmed/19794411", "http://www.ncbi.nlm.nih.gov/pubmed/21590310", "http://www.ncbi.nlm.nih.gov/pubmed/22122181", "http://www.ncbi.nlm.nih.gov/pubmed/21713343", "http://www.ncbi.nlm.nih.gov/pubmed/18034618", "http://www.ncbi.nlm.nih.gov/pubmed/19538716", "http://www.ncbi.nlm.nih.gov/pubmed/20615525", "http://www.ncbi.nlm.nih.gov/pubmed/19069171", "http://www.ncbi.nlm.nih.gov/pubmed/20210733", "http://www.ncbi.nlm.nih.gov/pubmed/19752777", "http://www.ncbi.nlm.nih.gov/pubmed/19135231", "http://www.ncbi.nlm.nih.gov/pubmed/16611750", "http://www.ncbi.nlm.nih.gov/pubmed/20854800", "http://www.ncbi.nlm.nih.gov/pubmed/11213860", "http://www.ncbi.nlm.nih.gov/pubmed/23342320", "http://www.ncbi.nlm.nih.gov/pubmed/18752379", "http://www.ncbi.nlm.nih.gov/pubmed/22952875" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_5131303833330011", "o": "http://purl.uniprot.org/core/Gene" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10524252", "o": "Gene" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/10524252", "o": "http://purl.uniprot.org/pubmed/10524252" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/10974568", "o": "http://purl.uniprot.org/pubmed/10974568" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/11587856", "o": "http://purl.uniprot.org/pubmed/11587856" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/11587856", "o": "http://purl.uniprot.org/pubmed/11587856" } ], "ideal_answer": [ "The following genes have been associated with patient response to warfarin: CYP2C9, VKORC1, ORM1, CYP4F2, EPHX1, CYP2C18, CYP2C19, CYP3A5, protein S, clotting factor V, PROC, GGCX." ], "exact_answer": [ [ "CYP2C9" ], [ "VKORC1" ], [ "ORM1" ], [ "CYP4F2" ], [ "EPHX1" ], [ "CYP2C18" ], [ "CYP2C19" ], [ "CYP3A5" ], [ "protein S" ], [ "clotting factor V" ], [ "PROC" ], [ "GGCX" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056426", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014644", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005819", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0047058", "http://www.biosemantics.org/jochem#4044132", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014859", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005823", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D036281", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0047057", "http://www.biosemantics.org/jochem#4044131", "http://www.biosemantics.org/jochem#4250139", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005826", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005815" ], "type": "list", "id": "5148885ad24251bc05000032", "snippets": [ { "offsetInBeginSection": 1005, "offsetInEndSection": 1199, "text": "We identified ORM1 as another polymorphic gene affecting warfarin dose requirements. ORM1 *S carriers require lower maintenance doses to achieve and maintain an optimal level of anticoagulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23208322", "endSection": "sections.0" }, { "offsetInBeginSection": 1877, "offsetInEndSection": 2078, "text": "Detecting genetic polymorphism of CYP2C9 and VKORC1 could guide clinical use of warfarin to reduce the risk of adverse reactions including bleeding in patients receiving chronic anticoagulation therapy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22321278", "endSection": "sections.0" }, { "offsetInBeginSection": 406, "offsetInEndSection": 622, "text": "The genes encoding for cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are the major genetic determinants of warfarin pharmacokinetics and pharmacodynamics, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122181", "endSection": "sections.0" }, { "offsetInBeginSection": 623, "offsetInEndSection": 914, "text": "Numerous studies have demonstrated significant contributions of these genes to warfarin dose requirements. The CYP2C9 gene has also been associated with bleeding risk with warfarin. The CYP4F2 gene influences vitamin K availability and makes minor contributions to warfarin dose requirements", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122181", "endSection": "sections.0" }, { "offsetInBeginSection": 367, "offsetInEndSection": 685, "text": "There are other genetic polymorphisms that may further explain the response to warfarin. The VKORC1 genotype is an important determinant of response to warfarin in Chinese, but some genetic variants found in other ethnic groups that have a large effect on warfarin response and dosing are not commonly found in Chinese", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023024", "endSection": "sections.0" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1379, "text": "the alleles rs1799853 (*2) and rs1057910 (*3) of the CYP2C9 gene, as well as rs9923231 of the VKORC1 gene were associated with warfarin dose required to achieve anticoagulation with INR of 2-3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21713343", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 200, "text": "Polymorphisms in the genes encoding the cytochrome P450 2C9 enzyme (CYP2C9) and the vitamin K epoxide reductase (VKORC1) are known to contribute to variability in sensitivity to coumarins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21651319", "endSection": "sections.0" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1329, "text": "VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21590310", "endSection": "sections.0" }, { "offsetInBeginSection": 13, "offsetInEndSection": 136, "text": "he response to the anticoagulant drug warfarin is greatly affected by genetic polymorphisms in the VKORC1 and CYP2C9 genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20854800", "endSection": "sections.0" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1339, "text": "The HDA-based assays demonstrated a clinically acceptable performance for genotyping the VKORC1 -1639G>A SNP and two SNPs (430C>T and 1075A>C) for the CYP2C9 enzyme (CYP2C9*2 and CYP2C9*3), all of which are relevant in warfarin pharmacogenentics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20854800", "endSection": "sections.0" }, { "offsetInBeginSection": 92, "offsetInEndSection": 192, "text": "Genetic variability in the VKORC1 and CYP2C9 genes is associated with increased warfarin sensitivity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20615525", "endSection": "sections.0" }, { "offsetInBeginSection": 74, "offsetInEndSection": 139, "text": "CYP2C9 and VKORC1 polymorphisms known to affect warfarin response", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20210733", "endSection": "sections.0" }, { "offsetInBeginSection": 542, "offsetInEndSection": 720, "text": "genetic variants of VKORC1, CYP2C9, CYP4F2, and EPHX1 were found to be significant predictor variables for the maintenance dose of warfarin, explaining 26.6% of dose variability.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19794411", "endSection": "sections.0" }, { "offsetInBeginSection": 561, "offsetInEndSection": 1032, "text": "CYP2C9 was the most important gene determining initial anticoagulant control, whereas VKORC1 was more important for stable anticoagulation. Novel associations with some clinical outcomes were found with single nucleotide polymorphisms in the cytochrome 450 genes CYP2C18 and CYP2C19, which were independent of the associations observed with CYP2C9 and in genes encoding CYP3A5, protein S and clotting factor V, although the variability explained by these genes was small.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19752777", "endSection": "sections.0" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1075, "text": "VKORC1 -1639 G>A polymorphism, body weight, age, and serum albumin were found to affect the inter-individual variabilit", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19135231", "endSection": "sections.0" }, { "offsetInBeginSection": 332, "offsetInEndSection": 423, "text": "the CYP2C9 and VKORC1 genes have been demonstrated to be determinants of warfarin response.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19069171", "endSection": "sections.0" }, { "offsetInBeginSection": 817, "offsetInEndSection": 1063, "text": "On the basis of these observations, the Food and Drug Administration (FDA) approved a labeling change for warfarin that includes the genetic information of VKORC1 and CYP2C9 as factors influencing interindividual variability in warfarin dosing. T", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19069171", "endSection": "sections.0" }, { "offsetInBeginSection": 275, "offsetInEndSection": 424, "text": "the two key genes of interest, the cytochrome P450 2C9 gene, CYP2C9, and the vitamin K epoxide reductase complex 1 gene, VKORC1, on warfarin response", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18752379", "endSection": "sections.0" }, { "offsetInBeginSection": 498, "offsetInEndSection": 708, "text": "The influence of CYP2C9 and VKORC1 genotypes on warfarin dose requirements has been consistently demonstrated in diverse racial and ethnic patient groups in observational studies and randomized clinical trials.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18752379", "endSection": "sections.0" }, { "offsetInBeginSection": 445, "offsetInEndSection": 701, "text": "genetic factors influencing drug pharmacokinetics (CYP2C9) and pharmacodynamic response (VKORC1). In particular, the discovery of polymorphisms in the VKORC1 gene that strongly impact oral anticoagulant dose has heightened expectations that genetic testing", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18464049", "endSection": "sections.0" }, { "offsetInBeginSection": 1402, "offsetInEndSection": 1686, "text": "Our data suggest that CYP2C9 genotype, age and body size are important determinants of warfarin dose requirements in African-Americans. Our data further suggest that the VKORC1 G6853C polymorphism alone may not be useful for predicting warfarin dose requirements in this racial group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18034618", "endSection": "sections.0" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1015, "text": "A strong association was found between genetic polymorphisms in six genes, including VKORC1, CYP2C9, PROC, EPHX1, GGCX, and ORM1, and interindividual variability in the anticoagulant effect of warfarin; the strongest predictors were VKORC1 and CYP2C9.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17496169", "endSection": "sections.0" }, { "offsetInBeginSection": 786, "offsetInEndSection": 961, "text": "Three of six VKORC1 SNPs were found to be very strongly associated with the average warfarin dose required to achieve the target international normalised ratio (INR; p<0.0001)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16611750", "endSection": "sections.0" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1741, "text": "These results are of considerable clinical interest and confirm recently published results regarding the role of these two genes in modifying warfarin metabolism and maintenance dosage. The consistent findings regarding the role of VKORC1 and CYP2C9 in warfarin metabolism and maintenance dosage represent a clinically useful proof of principal for the use of pharmacogenomic information in medicine and may lead to improved understanding of warfarin's actions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16611750", "endSection": "sections.0" }, { "offsetInBeginSection": 571, "offsetInEndSection": 780, "text": "Clinical studies showed an increased plasma level of S-warfarin, decreased clearance of S-warfarin, increased frequency of bleeding, and prolongation of hospitalization in patients with variant CYP2C9 alleles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11213860", "endSection": "sections.0" } ] }, { "body": "Which is the molecular weight of the protein angiogenin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7585697", "http://www.ncbi.nlm.nih.gov/pubmed/1723310", "http://www.ncbi.nlm.nih.gov/pubmed/18055286", "http://www.ncbi.nlm.nih.gov/pubmed/2775757", "http://www.ncbi.nlm.nih.gov/pubmed/10486275", "http://www.ncbi.nlm.nih.gov/pubmed/8574597", "http://www.ncbi.nlm.nih.gov/pubmed/10673358", "http://www.ncbi.nlm.nih.gov/pubmed/10441122", "http://www.ncbi.nlm.nih.gov/pubmed/4074709" ], "ideal_answer": [ "The molecular weight of angiogenin is 14,120 Da. The bovine angiogenin is 14,595 Da" ], "exact_answer": [ "14,120 Da" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014894", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008970", "http://www.uniprot.org/uniprot/ANGI_HUMAN", "http://www.uniprot.org/uniprot/ANGI_SAGOE", "http://www.uniprot.org/uniprot/ANGI_PYGBI", "http://www.uniprot.org/uniprot/ANGI_MOUSE", "http://www.uniprot.org/uniprot/ANGI_AOTTR", "http://www.uniprot.org/uniprot/ANGI_MACMU", "http://www.uniprot.org/uniprot/ANGI_MIOTA", "http://www.uniprot.org/uniprot/ANGI_PYGRO", "http://www.uniprot.org/uniprot/ANGI_SAISC" ], "type": "factoid", "id": "54d7ae1fe19bba8909000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Angiogenin is a potent blood-vessel-inducing polypeptide with a molecular weight of 14,000 that has a unique ribonucleolytic activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1723310", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 339, "text": " Bovine angiogenin is a single-chain protein of 125 amino acids; it contains six cysteines and has a calculated molecular weight of 14,595.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2775757", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 875, "text": "The amino acid composition of this basic (isoelectric point greater than 9.5), single-chain protein of molecular weight approximately 14 400 has been determined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4074709", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 536, "text": "was found to have a molecular weight of 15 kDa on SDS-PAGE, and the sequence of the N-terminal 25 amino acid residues was identical to that of bovine angiogenin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18055286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Human angiogenin is a 14-kDa plasma protein with angiogenic and ribonucleolytic activities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10673358", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 350, "text": " angiogenin-1 (15 kDa). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10486275", "endSection": "abstract" }, { "offsetInBeginSection": 1059, "offsetInEndSection": 1158, "text": "This protein is 14 kD in molecular weight, and is identical to the angioplastic factor angiogenin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8574597", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1156, "text": " angiogenin (M(r) = 14,120),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7585697", "endSection": "abstract" } ] }, { "body": "List sodium glucose co-transporter-2 (SGLT2) inhibitors that have been FDA approved for type 2 diabetes mellitus treatment.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24040872", "http://www.ncbi.nlm.nih.gov/pubmed/22632452", "http://www.ncbi.nlm.nih.gov/pubmed/25488697", "http://www.ncbi.nlm.nih.gov/pubmed/22433611", "http://www.ncbi.nlm.nih.gov/pubmed/24741548", "http://www.ncbi.nlm.nih.gov/pubmed/24455799", "http://www.ncbi.nlm.nih.gov/pubmed/25414933", "http://www.ncbi.nlm.nih.gov/pubmed/24585202", "http://www.ncbi.nlm.nih.gov/pubmed/25255411", "http://www.ncbi.nlm.nih.gov/pubmed/24059302", "http://www.ncbi.nlm.nih.gov/pubmed/25598831", "http://www.ncbi.nlm.nih.gov/pubmed/25688893", "http://www.ncbi.nlm.nih.gov/pubmed/24998153", "http://www.ncbi.nlm.nih.gov/pubmed/23194084", "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "http://www.ncbi.nlm.nih.gov/pubmed/24633706", "http://www.ncbi.nlm.nih.gov/pubmed/22583331", "http://www.ncbi.nlm.nih.gov/pubmed/19243283", "http://www.ncbi.nlm.nih.gov/pubmed/24025022", "http://www.ncbi.nlm.nih.gov/pubmed/24950857", "http://www.ncbi.nlm.nih.gov/pubmed/24705156", "http://www.ncbi.nlm.nih.gov/pubmed/25059406", "http://www.ncbi.nlm.nih.gov/pubmed/23729000", "http://www.ncbi.nlm.nih.gov/pubmed/22548646" ], "ideal_answer": [ "Canagliflozin, along with dapagliflozin and empagliflozin, are SGLT2 inhibitors approved by the US FDA for use in the treatment of type 2 diabetes." ], "exact_answer": [ [ "Dapagliflozin" ], [ "Empagliflozin" ], [ "Canagliflozin" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014486", "http://www.uniprot.org/uniprot/SC5A2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:9352", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017277", "http://www.uniprot.org/uniprot/SC5A2_RAT", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051297", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051273" ], "type": "list", "id": "571e189dbb137a4b0c000003", "snippets": [ { "offsetInBeginSection": 151, "offsetInEndSection": 319, "text": "Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998153", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 257, "text": "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 802, "text": " Empagliflozin is a new once-daily oral SGLT2 inhibitor with a mechanism of action that is independent of \u03b2-cell function and the insulin pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Sodium-glucose cotransporter type 2 (SGLT2) inhibitors such as canagliflozin and dapagliflozin have been approved for the treatment of type 2 diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 494, "text": "The present study emphasizes the molecular interactions between a new Food and Drug Administration (FDA) approved antidiabetic drug 'Invokana' (chemically known as Canagliflozin) with AChE and SGLT2 to establish a link between the treatment of T2DM and Alzheimer's Disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24059302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Invokana (Canagliflozin) as a dual inhibitor of acetylcholinesterase and sodium glucose co-transporter 2: advancement in Alzheimer's disease- diabetes type 2 linkage via an enzoinformatics study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24059302", "endSection": "title" }, { "offsetInBeginSection": 142, "offsetInEndSection": 296, "text": "This analysis assessed the effects of the SGLT2 inhibitor, canagliflozin, on model-based measures of beta cell function in patients with type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24585202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": " Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) promote the excretion of glucose to reduce glycated hemoglobin (HbA1c) levels. Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998153", "endSection": "abstract" }, { "offsetInBeginSection": 47, "offsetInEndSection": 247, "text": "a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Sodium glucose co-transporter 2 (SGLT2) inhibition with canagliflozin in type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025022", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Canagliflozin (Invokana\u2122), an oral selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, is under global development with Mitsubishi Tanabe Pharma and Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson, for the treatment of type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Invokana (Canagliflozin) as a dual inhibitor of acetylcholinesterase and sodium glucose co-transporter 2: advancement in Alzheimer's disease- diabetes type 2 linkage via an enzoinformatics study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24059302", "endSection": "title" }, { "offsetInBeginSection": 138, "offsetInEndSection": 306, "text": "Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998153", "endSection": "abstract" } ] }, { "body": "What is the gene mutated in the Gaucher disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8213821", "http://www.ncbi.nlm.nih.gov/pubmed/8556817", "http://www.ncbi.nlm.nih.gov/pubmed/11479729", "http://www.ncbi.nlm.nih.gov/pubmed/16039881", "http://www.ncbi.nlm.nih.gov/pubmed/8986634", "http://www.ncbi.nlm.nih.gov/pubmed/23936319", "http://www.ncbi.nlm.nih.gov/pubmed/20004604", "http://www.ncbi.nlm.nih.gov/pubmed/14757438", "http://www.ncbi.nlm.nih.gov/pubmed/1899336", "http://www.ncbi.nlm.nih.gov/pubmed/10882637", "http://www.ncbi.nlm.nih.gov/pubmed/21704274", "http://www.ncbi.nlm.nih.gov/pubmed/9733040", "http://www.ncbi.nlm.nih.gov/pubmed/9187679", "http://www.ncbi.nlm.nih.gov/pubmed/22230121", "http://www.ncbi.nlm.nih.gov/pubmed/21223590", "http://www.ncbi.nlm.nih.gov/pubmed/8051940", "http://www.ncbi.nlm.nih.gov/pubmed/7857677", "http://www.ncbi.nlm.nih.gov/pubmed/2464926", "http://www.ncbi.nlm.nih.gov/pubmed/17427031", "http://www.ncbi.nlm.nih.gov/pubmed/2117855", "http://www.ncbi.nlm.nih.gov/pubmed/2349952", "http://www.ncbi.nlm.nih.gov/pubmed/9175735", "http://www.ncbi.nlm.nih.gov/pubmed/9295080", "http://www.ncbi.nlm.nih.gov/pubmed/7923859" ], "ideal_answer": [ "The glucocerebrosidase gene (GBA)" ], "exact_answer": [ "glucocerebrosidase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005776", "http://www.disease-ontology.org/api/metadata/DOID:1926" ], "type": "factoid", "id": "532f55fed6d3ac6a34000036", "snippets": [ { "offsetInBeginSection": 127, "offsetInEndSection": 242, "text": "The glucocerebrosidase gene (GBA), located in a gene-rich region on chromosome 1q 21, is mutated in Gaucher disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21704274", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 143, "text": "(GD) is the most common of the lysosomal storage disorders and is caused by defects in the GBA gene encoding glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23936319", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 91, "text": "(GD) results from a deficiency of the lysosomal enzyme glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22230121", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 78, "text": "Gaucher disease is caused by defective glucocerebrosidase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21223590", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 71, "text": "Gaucher disease (GD), the inherited deficiency of glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20004604", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 73, "text": "utations in the glucocerebrosidase (GBA) gene cause Gaucher disease (GD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17427031", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 596, "text": "mutations in glucocerebrosidase (GBA) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16039881", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 122, "text": "GD) is a disorder of glycosphinglipid metabolism caused by deficiency of lysosomal acid beta-glucosidase ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16039881", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 134, "text": "Gaucher disease (GD) is a heterogeneous disease characterized by an impaired activity of the lysosomal glucocerebrosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14757438", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 276, "text": "Mutations in GBA may lead to Gaucher disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11479729", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 129, "text": "Gaucher's disease (GD) is an autosomal recessive disease produced by mutations of the Glucocerebrosidase gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10882637", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 97, "text": "aucher disease results, in most patients, from mutations in the gene encoding glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9733040", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 333, "text": "mutations in the glucocerebrosidase gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9295080", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 129, "text": "type I Gaucher disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9295080", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 394, "text": "complete deletion of the beta-glucocerebrosidase gene was investigated in 25 unrelated non-Jewish patients with Gaucher's disease ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9187679", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 120, "text": "aucher disease is a heterogeneous disease characterized by impaired activity of the lysosomal enzyme glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9175735", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 97, "text": "aucher disease, resulting from the decreased activity of the lysosomal enzyme glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8986634", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 148, "text": "screening of the glucocerebrosidase gene by SSCP analysis revealed an abnormal pattern of exon 10 in two unrelated Italian Gaucher patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8556817", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 74, "text": "GD) is an inherited deficiency of beta-glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7857677", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 160, "text": "Gaucher disease is type 1. The N370S glucocerebrosidase gene mutation accounts for 63% of mutated alleles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7923859", "endSection": "abstract" }, { "offsetInBeginSection": 43, "offsetInEndSection": 115, "text": "mutated glucocerebrosidase alleles of Portuguese type 1 Gaucher patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8051940", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 132, "text": "mutated alleles known to occur in the glucocerebrosidase gene was determined in 247 Gaucher patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8213821", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 264, "text": "Gaucher disease has marked phenotypic variation and molecular heterogeneity, and several simple and complex alleles of the acid beta-glucosidase gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1899336", "endSection": "abstract" }, { "offsetInBeginSection": 49, "offsetInEndSection": 193, "text": "Gaucher disease in 3 successive generations were tested for the presence of the 2 common mutations known to occur in the glucocerebrosidase gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2117855", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 262, "text": "Gaucher disease has marked phenotypic variation and molecular heterogeneity, and seven point mutations in the acid beta-glucosidase (beta-Glc) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2349952", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 147, "text": "cDNA clones containing the entire coding sequence of human glucocerebrosidase were isolated from libraries originated from Gaucher patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2464926", "endSection": "abstract" } ] }, { "body": "Why does the prodrug amifostine (ethyol) create hypoxia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "http://www.ncbi.nlm.nih.gov/pubmed/11597323", "http://www.ncbi.nlm.nih.gov/pubmed/21590129", "http://www.ncbi.nlm.nih.gov/pubmed/20334641", "http://www.ncbi.nlm.nih.gov/pubmed/17602063", "http://www.ncbi.nlm.nih.gov/pubmed/11984063", "http://www.ncbi.nlm.nih.gov/pubmed/8783669", "http://www.ncbi.nlm.nih.gov/pubmed/11379297", "http://www.ncbi.nlm.nih.gov/pubmed/8976819", "http://www.ncbi.nlm.nih.gov/pubmed/19182669", "http://www.ncbi.nlm.nih.gov/pubmed/23154884", "http://www.ncbi.nlm.nih.gov/pubmed/11712796", "http://www.ncbi.nlm.nih.gov/pubmed/14574457" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17889382", "o": "N0000022033" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A17889382" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17889382", "o": "AMIFOSTINE/MANNITOL" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A12102802" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A17985952" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17985952", "o": "N0000022033" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12102802", "o": "4024028" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10414743", "o": "330576" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10414743", "o": "Amifostine 50 MG/ML" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1126264", "o": "http://linkedlifedata.com/resource/umls/label/A10414743" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10488633", "o": "RXNORM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1251303", "o": "http://linkedlifedata.com/resource/umls/label/A10488633" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1251303", "o": "http://linkedlifedata.com/resource/umls/label/A10488633" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10488633", "o": "Amifostine Injectable Solution" } ], "ideal_answer": [ "After the administration of Prodrug amifostine the cells of the tissue prefer anaerobic glycolysis rather than regular cellular aerobic respiration. By the beggining of anaerobic glycolysis the inducible by hypoxia proteins are induced and by all these molecules the hypoxic conditions consist of." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071456", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015687", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001666", "http://www.biosemantics.org/jochem#4217067", "http://www.biosemantics.org/jochem#4277891", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000860", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004999" ], "type": "summary", "id": "533eba45c45e133714000014", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 261, "text": "Amifostine (WR-2721, delivered as Ethyol) is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334641", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 671, "text": "However, amifostine has also been described as a potent hypoxia-mimetic compound and as a strong p53 inducer; both effects are known to potently modulate vascular endothelial growth factor (VEGF-A) expression. The angiogenic properties of this drug have not been clearly defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334641", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1158, "text": "Both dose fractionation and amifostine protect osteoblasts from the growth inhibitory effects of ionizing radiation. Fractionation but not amifostine was protective for hypoxia-induced vascular endothelial growth factor production (used as a surrogate marker of normal osteoblast function)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19182669", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 451, "text": "Radioprotective modalities such as dose fractionation and pharmacologic agents such as amifostine have been used to protect bone and other types of normal tissue from the damaging effects of ionizing radiation without significantly impacting tumor kill. To better understand the cellular mechanism of radioprotection of osseous tissue, the authors sought to determine the effect of dose fractionation and amifostine on isolated osteoblasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19182669", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 364, "text": "Tumor hypoxia and low intrinsic radiosensitivity may counteract the efficacy of standard radiotherapy for locally advanced head and neck cancer (HNC). We investigated the involvement of hypoxia-regulated proteins (Hypoxia inducible factors HIF1alpha, HIF2alpha and carbonic anhydrase CA9) in HNC resistance to accelerated and hypofractionated radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 864, "text": " Immunohistochemical analysis of hypoxia-regulated proteins, namely HIF1alpha, HIF2alpha and CA9, was performed in formalin-fixed paraffin-embedded tissues obtained prior to radio-chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1867, "text": "In accord with previously reported studies, high levels of the hypoxia regulated proteins HIF1alpha and CA9 in HNC predict resistance to platinum based radio-chemotherapy. Whether HIF2alpha expressing tumors are more sensitive to larger radiotherapy fractions, compared to standard radiotherapy fractionation, is an issue that deserves further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 760, "text": "Amifostine has been shown to specifically protect normal tissues from damage caused by radiation and chemotherapy. An inactive prodrug, amifostine is converted to an active thiol by dephosphorylation by alkaline phosphatase in the normal endothelium. The hypovascularity and acidity of the tumor environment and the differential expression of alkaline phosphatase in normal and neoplastic tissues contribute to its cytoprotective selectivity. The cytoprotective mechanism of amifostine is complicated, involving free-radical scavenging, DNA protection and repair acceleration, and induction of cellular hypoxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17602063", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 389, "text": "We investigated additional cytoprotective pathways involving intracellular hypoxia and the activation of the hypoxia-inducible factor (HIF) pathway, a key transcription factor regulating glycolysis, angiogenesis and apoptosis, which is also linked with radioresistance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14574457", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 587, "text": " tumor hypoxia and ability of cancer cells to undergo rapid repopulation during radiotherapy are associated with failure of radiotherapy. Tumors with low alpha/beta-ratio values or hypoxic tumors unable to undergo re-oxygenation, are unlikely to be eradicated with standard radiotherapy. Although the therapeutic efficacy of accelerated regimens based on low-dose per fraction may be high since they minimize the adverse role of rapid tumor repopulation, the cellular compartment with low alpha/beta-ratio values (i.e. hypoxic cells) remains a limiting factor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11712796", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 878, "text": "Amifostine (Ethyol) is a prodrug that must be dephosphorylated to the free thiol in which form it can detoxify free oxygen radicals generated by radiation, hypoxia and by drugs such anthracyclines, platinum analogues and alkylating agents. Amifostine as inactive prodrug is primarily metabolized at the tissue site by membrane alkaline phosphatase, which is highly active in the cell membranes of normal endothelial cells and biliary tree cells but not in the cell membranes and neovascular capillaries of tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11379297", "endSection": "abstract" } ] }, { "body": "What is considered a reliable technique for the definitive cytogenetic diagnosis of Fanconi anemia homozygosity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19278965", "http://www.ncbi.nlm.nih.gov/pubmed/8374893", "http://www.ncbi.nlm.nih.gov/pubmed/22052692", "http://www.ncbi.nlm.nih.gov/pubmed/3133104" ], "ideal_answer": [ "In vitro enhancement of chromosome breakage by diepoxybutane (DEB) and mitomycin C (MMC) are reliable techniques for the definitive cytogenetic diagnosis of Fanconi anemia homozygosity.", "In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020732", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "summary", "id": "54eded8c94afd6150400000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "The in vitro enhancement of chromosome breakage by diepoxybutane (DEB) and mitomycin C (MMC) was studied in 24 Fanconi's anemia (FA) homozygotes and 28 heterozygotes. Both drugs were shown to enhance chromosome breakage significantly in the homozygotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3133104", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 391, "text": "In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3133104", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 390, "text": " In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3133104", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 512, "text": "The diagnosis of Fanconi anemia was confirmed by increased chromosomal breakage abnormalities observed in cultured cells that were treated with cross-linking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22052692", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 392, "text": "In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3133104", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 396, "text": "The cytogenetic test was shown to be reliable in ascertaining the diagnosis of FA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8374893", "endSection": "abstract" }, { "offsetInBeginSection": 1867, "offsetInEndSection": 2038, "text": "For that purpose, the flow-based mitomycin C sensitivity test here described proved to be a reliable alternative method to evaluate Fanconi anemia phenotype in fibroblasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19278965", "endSection": "abstract" } ] }, { "body": "Can exosomes be detected in urine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24250247", "http://www.ncbi.nlm.nih.gov/pubmed/24315007", "http://www.ncbi.nlm.nih.gov/pubmed/24205503", "http://www.ncbi.nlm.nih.gov/pubmed/24101370", "http://www.ncbi.nlm.nih.gov/pubmed/24196483", "http://www.ncbi.nlm.nih.gov/pubmed/24044569", "http://www.ncbi.nlm.nih.gov/pubmed/24060994", "http://www.ncbi.nlm.nih.gov/pubmed/24069349", "http://www.ncbi.nlm.nih.gov/pubmed/23585095", "http://www.ncbi.nlm.nih.gov/pubmed/24058411" ], "ideal_answer": [ "Yes, urinary exosomes can be detected in urine." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014556", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055354" ], "type": "yesno", "id": "550895c12e93f0133a000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Exosomes are nanovesicles secreted into the extracellular environment upon internal vesicle fusion with the plasma membrane. The molecular content of exosomes is a fingerprint of the releasing cell type and of its status. For this reason, and because they are released in easily accessible body fluids such as blood and urine, they represent a precious biomedical tool. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24044569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Exosomes are vesicles that are released from the kidney into urine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24060994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Quantification of human urinary exosomes by nanoparticle tracking analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24060994", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24069349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Urinary exosomes have been proposed as potential diagnostic tools.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24315007", "endSection": "title" }, { "offsetInBeginSection": 73, "offsetInEndSection": 231, "text": ". Here we sought to optimize the methodologies for the isolation and quantification of urinary exosomal microRNA as a prelude to biomarker discovery studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24250247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Exosomes are small (30-150\u2009nm) vesicles containing unique RNA and protein cargo, secreted by all cell types in culture. They are also found in abundance in body fluids including blood, saliva, and urine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24205503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40-200\u2009nm) containing vesicles shed from all segments of the nephron including glomerular podocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24196483", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "Exosomes are cytoplasm containing vesicles released by many cells that can be found in several biological fluids including urine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Proteomic analysis of urinary exosomes in cardiovascular and associated kidney diseases by two-dimensional electrophoresis and LC-MS/MS", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23585095", "endSection": "title" } ] }, { "body": "What is the role of lysine-specific demethylase 1 (LSD1) in hematopoiesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "http://www.ncbi.nlm.nih.gov/pubmed/19736520", "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "http://www.ncbi.nlm.nih.gov/pubmed/22399799" ], "ideal_answer": [ "LSD1 represents a central regulator of hematopoietic stem and progenitor cells. LSD1 knockdown (LSD1-kd) expanded progenitor numbers by enhancing their proliferative behavior. LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors. In contrast, terminal granulopoiesis, erythropoiesis and platelet production were severely inhibited. The only exception was monopoiesis, which was promoted by LSD1 deficiency. Importantly, we showed that peripheral blood granulocytopenia, monocytosis, anemia and thrombocytopenia were reversible after LSD1-kd termination. Extramedullary splenic hematopoiesis contributed to the phenotypic reversion, and progenitor populations remained expanded. LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, Hoxa9 and Meis1, which are known regulators of the HSC/progenitor compartment. We also demonstrated that LSD1-kd abrogated Gfi1b-negative autoregulation by crossing LSD1-kd with Gfi1b:GFP mice. There is also epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b that is mediated by the cofactors CoREST and LSD1. A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain. The enzymatic domain of LSD1 plays an important role in repressing the TAL1-directed transcription of GAL4 reporter linked to a thymidine kniase minimal promoter. Furthermore, the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation. Consistent with the rapid changes of TAL1-corepressor complex during differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells. ShRNA-mediated knockdown of LSD1 in MEL cells resulted in derepression of the TAL1 target gene accompanied by increasing dimeH3K4 at the promoter region. Thus, it appears that histone lysine demethylase LSD1 may negatively regulate TAL1-mediated transcription and that the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs. Furthermore, RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 in erythroid cells. RUNX1 interacts with LSD1 and MYEF2 in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Finally, LSD1 also participates in the trans-repressive effects of SALL4. Based on luciferase assays, the amine oxidase domain of LSD1 is important in suppressing SALL4-mediated reporter transcription. In freshly isolated adult mouse bone marrows, both SALL4 and LSD1 proteins are preferentially expressed in undifferentiated progenitor cells and co-localize in the nuclei. Further sequential chromatin immunoprecipitation assay confirmed that these two factors share the same binding sites at the promoter regions of important hematopoietic regulatory genes including EBF1, GATA1, and TNF." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033193" ], "type": "summary", "id": "55435a46ed966d112c000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "title" }, { "offsetInBeginSection": 285, "offsetInEndSection": 699, "text": "we demonstrate that LSD1, a histone lysine demethylase, also participates in the trans-repressive effects of SALL4. Based on luciferase assays, the amine oxidase domain of LSD1 is important in suppressing SALL4-mediated reporter transcription. In freshly isolated adult mouse bone marrows, both SALL4 and LSD1 proteins are preferentially expressed in undifferentiated progenitor cells and co-localize in the nuclei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 916, "text": "Further sequential chromatin immunoprecipitation assay confirmed that these two factors share the same binding sites at the promoter regions of important hematopoietic regulatory genes including EBF1, GATA1, and TNF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1560, "text": "our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 631, "text": "RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 (N. Meier et al., Development 133:4913-4923, 2006) in erythroid cells. We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "title" }, { "offsetInBeginSection": 327, "offsetInEndSection": 1499, "text": "LSD1 represents a central regulator of hematopoietic stem and progenitor cells. LSD1 knockdown (LSD1-kd) expanded progenitor numbers by enhancing their proliferative behavior. LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors. In contrast, terminal granulopoiesis, erythropoiesis and platelet production were severely inhibited. The only exception was monopoiesis, which was promoted by LSD1 deficiency. Importantly, we showed that peripheral blood granulocytopenia, monocytosis, anemia and thrombocytopenia were reversible after LSD1-kd termination. Extramedullary splenic hematopoiesis contributed to the phenotypic reversion, and progenitor populations remained expanded. LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, Hoxa9 and Meis1, which are known regulators of the HSC/progenitor compartment. We also demonstrated that LSD1-kd abrogated Gfi1b-negative autoregulation by crossing LSD1-kd with Gfi1b:GFP mice. Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799", "endSection": "title" }, { "offsetInBeginSection": 468, "offsetInEndSection": 629, "text": "Gfi-1B p32 isoform binds to Gfi-1B target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major Gfi-1B p37 isoform", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 962, "text": "Furthermore, we show that Gfi-1B includes a KSKK motif in its SNAG domain, which recruits the repressor complex only when dimethylated on lysine 8. Mutation of lysine 8 prevents Gfi-1B p32-induced erythroid development. Our results thus highlight a key role for the alternatively spliced Gfi-1B p32 isoform in erythroid development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 1362, "text": "we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis. Knockdown of TAL1 or LSD1 led to a derepression of the TAL1 target genes in T-cell acute lymphoblast leukemia (T-ALL) Jurkat cells, which is accompanied by elevating promoter H3K4 methylation. Similarly, treatment of PKA activator forskolin resulted in derepression of target genes by reducing its interaction with LSD1 while PKA inhibitor H89 represses them by suppressing H3K4 methylation levels. Consistent with the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased while recruitment of hSET1 is increased at the TAL1 targets during erythroid differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 415, "text": "TAL1 has recently been shown to differentially recruit LSD1 and other histone modifying complexes to regulate its target genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19736520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 525, "text": "we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 1508, "text": "The enzymatic domain of LSD1 plays an important role in repressing the TAL1-directed transcription of GAL4 reporter linked to a thymidine kniase minimal promoter. Furthermore, we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation. Consistent with the rapid changes of TAL1-corepressor complex during differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells. Finally, shRNA-mediated knockdown of LSD1 in MEL cells resulted in derepression of the TAL1 target gene accompanied by increasing dimeH3K4 at the promoter region. Thus, our data revealed that histone lysine demethylase LSD1 may negatively regulate TAL1-mediated transcription and suggest that the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "endSection": "title" }, { "offsetInBeginSection": 223, "offsetInEndSection": 590, "text": "To elucidate the function of Gfi proteins, we purified Gfi-1b complexes and identified interacting proteins. Prominent among these is the corepressor CoREST, the histone demethylase LSD1, and HDACs 1 and 2. CoREST and LSD1 associate with Gfi-1/1b via the SNAG repression domain. Gfi-1b further recruits these cofactors to the majority of target gene promoters in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1489, "text": "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "title" }, { "offsetInBeginSection": 547, "offsetInEndSection": 775, "text": "Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "title" }, { "offsetInBeginSection": 1336, "offsetInEndSection": 1500, "text": "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" } ] }, { "body": "For the treatment of which conditions can atypical neuroleptic drugs be used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16625511", "http://www.ncbi.nlm.nih.gov/pubmed/10440458", "http://www.ncbi.nlm.nih.gov/pubmed/16047503", "http://www.ncbi.nlm.nih.gov/pubmed/11533860", "http://www.ncbi.nlm.nih.gov/pubmed/7952245", "http://www.ncbi.nlm.nih.gov/pubmed/1618284", "http://www.ncbi.nlm.nih.gov/pubmed/8891947", "http://www.ncbi.nlm.nih.gov/pubmed/12596031", "http://www.ncbi.nlm.nih.gov/pubmed/10746298", "http://www.ncbi.nlm.nih.gov/pubmed/9384923", "http://www.ncbi.nlm.nih.gov/pubmed/17347940", "http://www.ncbi.nlm.nih.gov/pubmed/10320209" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8360847", "o": "94.23" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17351788", "o": "Neuroleptic therapy" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1281543", "o": "http://linkedlifedata.com/resource/umls/label/A8360847" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1281543", "o": "http://linkedlifedata.com/resource/umls/label/A17351788" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1281543", "o": "http://linkedlifedata.com/resource/umls/label/A17351788" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8360847", "o": "ICD-9-CM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17351788", "o": "Metathesaurus Names" } ], "ideal_answer": [ "Atypical neuroloeptic drugs are antipsychotics used in patients with schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders, psychotic relapse in neuroleptic malignant syndrome and attention deficit hyperactivity disorder when presenting with negativism and conduct disorder." ], "exact_answer": [ [ "schizophrenia", "schizophrenia psychosis" ], [ "schizoaffective disorder" ], [ "delusional disorder" ], [ "psychotic relapse in neuroleptic malignant syndrome" ], [ "attention deficit hyperactivity disorder (ADHD) with negativism or conduct disorders" ], [ "psychotic disorders" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016320", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014150", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ], "type": "list", "id": "52bf1f4503868f1b06000016", "snippets": [ { "offsetInBeginSection": 1297, "offsetInEndSection": 1554, "text": "Further clinical implications are described (capability of learning the therapeutic strategies, deliverability in broader clinical settings, acceptability by patients, combination with atypical neuroleptic drugs,and treatment of choice in risk populations).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12596031", "endSection": "abstract" }, { "offsetInBeginSection": 1784, "offsetInEndSection": 1993, "text": "Intervention strategies are a multimodal psychological programme for the intervention in early prodromal stages and a combination of psychotherapy with atypical neuroleptic drugs in the late prodromal stages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11533860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Atypical neuroleptic drugs have enriched our treatment programs, especially in childhood and adolescent schizophrenia. Reviewed here is the use of atypical neuroleptics in children and adolescents with a schizophrenic disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10746298", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 400, "text": "o prove whether weight gain is a relevant side effect of atypical neuroleptics, the charts of all patients admitted with DSM-III-R diagnoses of schizophrenia, schizoaffective disorder, or delusional disorder in the years 1991 to 1995 were evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10440458", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 364, "text": "The handwriting of 18 schizophrenic patients before and during treatment with typical (haloperidol, haloperidol decanoate) and atypical (clozapine, risperidone) neuroleptic drugs was examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10320209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Atypical and typical neuroleptics, when administered chronically, can bring about profound but contrasting changes in schizophrenic symptoms and motor activation and dramatically modulate brain neurochemistry", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8891947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Recent studies suggest that clozapine is more effective than typical neuroleptics for patients with treatment-resistant schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9384923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Acute and late onset movement disorders frequently complicate the treatment of psychosis with typical neuroleptic drugs like haloperidol, but not with atypical neuroleptic drugs like clozapine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1618284", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1224, "text": "Only the group of boys presented other comorbidities such as negativism and conduct disorders; approximately 25% of them required treatment with atypical neuroleptic drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17347940", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 480, "text": "Atypical neuroleptic drugs are the preferred treatment for symptoms such as delusions, hallucinations, agitation and aggressive behaviour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16625511", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 904, "text": "Monotherapeutic treatment with new atypical neuroleptic drugs had a more positive effect on the mental health related quality of life (MCS) in comparison to treatment with polypharmacological treatment but not with oral conventional antipsychotics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16047503", "endSection": "abstract" } ] }, { "body": "Which are the characteristics of Andersen syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12689820", "http://www.ncbi.nlm.nih.gov/pubmed/15176430", "http://www.ncbi.nlm.nih.gov/pubmed/20306271", "http://www.ncbi.nlm.nih.gov/pubmed/15831539", "http://www.ncbi.nlm.nih.gov/pubmed/22589293", "http://www.ncbi.nlm.nih.gov/pubmed/17119796", "http://www.ncbi.nlm.nih.gov/pubmed/12148092", "http://www.ncbi.nlm.nih.gov/pubmed/17395133", "http://www.ncbi.nlm.nih.gov/pubmed/16571646", "http://www.ncbi.nlm.nih.gov/pubmed/17272325", "http://www.ncbi.nlm.nih.gov/pubmed/16859779", "http://www.ncbi.nlm.nih.gov/pubmed/12032359", "http://www.ncbi.nlm.nih.gov/pubmed/20609799", "http://www.ncbi.nlm.nih.gov/pubmed/10406668", "http://www.ncbi.nlm.nih.gov/pubmed/16769944", "http://www.ncbi.nlm.nih.gov/pubmed/17399643", "http://www.ncbi.nlm.nih.gov/pubmed/20382953", "http://www.ncbi.nlm.nih.gov/pubmed/12536108", "http://www.ncbi.nlm.nih.gov/pubmed/12909315", "http://www.ncbi.nlm.nih.gov/pubmed/19445372", "http://www.ncbi.nlm.nih.gov/pubmed/8080508", "http://www.ncbi.nlm.nih.gov/pubmed/16877549", "http://www.ncbi.nlm.nih.gov/pubmed/23644778", "http://www.ncbi.nlm.nih.gov/pubmed/10190827", "http://www.ncbi.nlm.nih.gov/pubmed/15269659", "http://www.ncbi.nlm.nih.gov/pubmed/18554214", "http://www.ncbi.nlm.nih.gov/pubmed/21317470", "http://www.ncbi.nlm.nih.gov/pubmed/17582433", "http://www.ncbi.nlm.nih.gov/pubmed/19570891" ], "ideal_answer": [ "the characteristics of Andersen syndrome are abnormal QT-U complex, ventricular arrhythmia, periodic paralysis, and facial and skeletal dysmorphisms" ], "exact_answer": [ [ "abnormal QT-U complex" ], [ "ventricular arrhythmia" ], [ "periodic paralysis" ], [ "facial dysmorphisms" ], [ "skeletal dysmorphisms" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050030" ], "type": "list", "id": "52eeddfcc8da898910000010", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 229, "text": "Mutations of KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1, cause Andersen-Tawil syndrome (ATS), a disease exhibiting ventricular arrhythmia, periodic paralysis, and dysmorphic features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Andersen cardiodysrhythmic periodic paralysis or Andersen-Tawil syndrome includes the distinct clinical features of periodic paralysis, cardiac arrhythmia, and facial and skeletal dysmorphisms and exhibits autosomal dominant inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382953", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 244, "text": "The patient was a 19-year-old woman with familial periodic paralysis, abnormal QT-U complex, and nonsustained ventricular tachycardia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17399643", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 265, "text": "Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16571646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 655, "text": "Evaluation of candidate loci culminated in the identification of a heterozygous missense mutation (R67W) in KCNJ2, the gene encoding the inward-rectifying potassium current, Kir2.1, in 41 members of a kindred in which ventricular arrhythmias (13 of 16 female members [81%]) and periodic paralysis (10 of 25 male members [40%]) segregated as autosomal dominant traits with sex-specific variable expressivity. Some mutation carriers exhibited dysmorphic features, including hypertelorism, small mandible, syndactyly, clinodactyly, cleft palate, and scoliosis, which, together with cardiodysrhythmic periodic paralysis, have been termed \"Andersen syndrome.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12148092", "endSection": "abstract" } ] }, { "body": "How are induced pluripotent stem cells used in the study and treatment of cardiovascular diseases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21919874", "http://www.ncbi.nlm.nih.gov/pubmed/23229562", "http://www.ncbi.nlm.nih.gov/pubmed/22917225", "http://www.ncbi.nlm.nih.gov/pubmed/21569778", "http://www.ncbi.nlm.nih.gov/pubmed/23896987", "http://www.ncbi.nlm.nih.gov/pubmed/22447279", "http://www.ncbi.nlm.nih.gov/pubmed/23390563", "http://www.ncbi.nlm.nih.gov/pubmed/21527744", "http://www.ncbi.nlm.nih.gov/pubmed/23819949", "http://www.ncbi.nlm.nih.gov/pubmed/21451408", "http://www.ncbi.nlm.nih.gov/pubmed/22385148", "http://www.ncbi.nlm.nih.gov/pubmed/23292032", "http://www.ncbi.nlm.nih.gov/pubmed/23955788", "http://www.ncbi.nlm.nih.gov/pubmed/24298311" ], "ideal_answer": [ "The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. The production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and cardiotoxicity screening. In addition, the ability to derive human-induced pluripotent stem cells from somatic tissues, combined with current high-throughput screening and pharmacogenomics, may help realize the use of these cells to fulfill the potential of personalized medicine. Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study \"disease in a dish\" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. Long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia are two heart rhythm disorders that have been already successfully modeled by several groups using this approach, which will likely serve to model other mono- or polygenetic cardiovascular disorders in the future. The use of iPSC-derived cardiomyocytes to study genetic cardiovascular disorders will enable a deeper and more applicable understanding of the molecular mechanisms of human disease, as well as improving our ability to achieve successful cell-based therapies." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2348", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057026", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039904", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013234", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318" ], "type": "summary", "id": "54fc48bb6ea36a810c000002", "snippets": [ { "offsetInBeginSection": 187, "offsetInEndSection": 375, "text": "iPSC technology holds tremendous promises for therapeutic cardiovascular regeneration because of the cells' unlimited capacity for proliferation and differentiation into all cell lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298311", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 1113, "text": "The iPSCs can be generated from somatic cells of patients with a genetic basis for their disease so as to understand the pathobiology of the disorder. This disease modeling can be adapted to high-throughput screens to discover new therapeutic molecules. Finally, the iPSC technology may enable personalized cell therapies, while avoiding the ethical concerns surrounding human embryonic stem cells. Intensive efforts are underway to develop reliable methods to guide stem cell differentiation into cardiovascular lineages in the treatment of peripheral artery disease and heart diseases. Studies of disease pathogenesis and drug discovery using iPSC technology shall advance the discovery of novel treatments for cardiovascular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Induced pluripotent stem cells: how they will change the practice of cardiovascular medicine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298311", "endSection": "title" }, { "offsetInBeginSection": 424, "offsetInEndSection": 626, "text": "Since the first description of human induced pluripotent stem cell-derived cardiomyocytes, these cells have garnered tremendous interest for their potential use in patient-specific analysis and therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955788", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 1435, "text": "The promise of successful therapies with stem cells to treat these conditions has remained elusive to the scientific community. However, recent advances in this field have opened new opportunities for regenerative cardiac therapy. Transplantation of cardiomyocytes derived from human pluripotent stem cells has the potential to alleviate heart disease. Since the initial derivation of human embryonic stem cells, significant progress has been made in the generation and characterization of enriched cardiomyocytes and the demonstration of the ability of these cardiomyocytes to survive, integrate, and function in animal models. The scope of therapeutic potential from pluripotent stem cell-derived cardiomyocytes has been further expanded with the invention of induced pluripotent stem cells, which can be induced to generate functional cardiomyocytes for regenerative cardiac therapy in a patient specific manner. The reprogramming technology has also inspired the recent discovery of direct conversion of fibroblasts into cardiomyocyte-like cells, which may allow endogenous cardiac repair. Regenerative cardiac therapy with human pluripotent stem cells is now moving closer to clinic testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23819949", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 637, "text": " Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study \"disease in a dish\" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. They also provide an exciting opportunity for drug discovery and drug repurposing for disorders with a known molecular basis including childhood onset heart disease, particularly cardiac genetic disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23292032", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 1017, "text": "The in vitro production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and cardiotoxicity screening. In addition, the ability to derive human-induced pluripotent stem cells from somatic tissues, combined with current high-throughput screening and pharmacogenomics, may help realize the use of these cells to fulfill the potential of personalized medicine. In this review, we discuss the use of pluripotent stem cell-derived cardiomyocytes for drug discovery and cardiotoxicity screening, as well as current hurdles that must be overcome for wider clinical applications of this promising approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229562", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 681, "text": "The progress made toward the generation of induced Pluripotent Stem (iPS) cells hold great potential for future use in myocardial repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22917225", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 543, "text": "Cardiovascular diseases are still the leading cause of death worldwide. Despite the improvement shown in the prognosis of patients with acute MI, there remains still a significant mortality risk. Since the main underlying problem after an MI is the loss of cardiomyocytes and microvasculature, treatment strategies aimed at preserving or regenerating myocardial tissue have been examined as potential therapeutic modalities. Toward this goal, many cell types are being investigated as potent sources of cardiomyocytes for cell transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22917225", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSC) by overexpression of a combination of transcription factors bears the potential to spawn a wealth of new applications in both preclinical and clinical cardiovascular research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22447279", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 1204, "text": "Disease modeling, which is accomplished by deriving iPSC lines from patients affected by heritable diseases and then studying the pathophysiology of the diseases in somatic cells differentiated from these patient-specific iPSC lines, is the so far most advanced of these applications. Long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia are two heart rhythm disorders that have been already successfully modeled by several groups using this approach, which will likely serve to model other mono- or polygenetic cardiovascular disorders in the future. Test systems based on cells derived from iPSC might prove beneficial to screen for novel cardiovascular drugs or unwanted drug side effects and to individualize medical therapy. The application of iPSC for cell therapy of cardiovascular disorders, albeit promising, will only become feasible if the problem of biological safety of these cells will be mastered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22447279", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 728, "text": "The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, for cell transplantation or disease modelling using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22385148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Stem cells in cardiovascular regeneration: from preservation of endogenous repair to future cardiovascular therapies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21919874", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 811, "text": "Cardiovascular disease remains the leading cause of morbidity and mortality in the developed countries. This review summarizes current pre-clinical and clinical evidence for the potential role and mechanisms of action of stem and progenitor cells in vascular and cardiac repair and regeneration. Apart from cell transplantation strategies, approaches to maintain stem cell niche function and targeting mobilization/recruitment of specific stem/progenitor cell populations may aid in preserving vascular and cardiac function. Moreover, with the use of patient-derived induced pluripotent stem cells, the field of regenerative medicine is entering a new era. Potential applications of induced pluripotent stem cells and direct reprogrammed cells as well as recent developments in tissue engineering are discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21919874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "The successful derivation of human induced pluripotent stem cells (hiPSCs) by dedifferentiation of somatic cells offers significant potential to overcome obstacles in the field of cardiovascular disease. hiPSC derivatives offer incredible potential for new disease models and regenerative medicine therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527744", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 315, "text": "The development of induced pluripotent stem cell (iPSC) technology has led to many advances in the areas of directed cell differentiation and characterization. New methods for generating iPSC-derived cardiomyocytes provide an invaluable resource for the study of certain cardiovascular disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21451408", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 525, "text": "This review highlights the current technology in this field, its application thus far to the study of genetic disorders of the RAS/MAPK pathway and long-QT syndrome (LQTS), and future directions for the field.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21451408", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 843, "text": "The use of cardiomyocytes derived from patients with LEOPARD syndrome and LQTS has shed light on the molecular mechanisms of disease and validated their use as reliable human disease models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21451408", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1111, "text": "The use of iPSC-derived cardiomyocytes to study genetic cardiovascular disorders will enable a deeper and more applicable understanding of the molecular mechanisms of human disease, as well as improving our ability to achieve successful cell-based therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21451408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) are promising for treatment of vascular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Human induced pluripotent stem (iPS) cells potentially provide a unique resource for generating patient-specific cardiomyocytes to study cardiac disease mechanisms and treatments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21569778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 402, "text": "Cardiovascular progenitor cells (CVPCs) derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold great promise for the study of cardiovascular development and cell-based therapy of heart diseases, but their applications are challenged by the difficulties in their efficient generation and stable maintenance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23896987", "endSection": "abstract" } ] }, { "body": "Which disease is included as an additional feature in the Goldberg-Shprintzen syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12878302", "http://www.ncbi.nlm.nih.gov/pubmed/7573130", "http://www.ncbi.nlm.nih.gov/pubmed/7573131", "http://www.ncbi.nlm.nih.gov/pubmed/18192286", "http://www.ncbi.nlm.nih.gov/pubmed/23023332", "http://www.ncbi.nlm.nih.gov/pubmed/1785632", "http://www.ncbi.nlm.nih.gov/pubmed/23427148", "http://www.ncbi.nlm.nih.gov/pubmed/8563763", "http://www.ncbi.nlm.nih.gov/pubmed/12846610", "http://www.ncbi.nlm.nih.gov/pubmed/23984569", "http://www.ncbi.nlm.nih.gov/pubmed/22639450", "http://www.ncbi.nlm.nih.gov/pubmed/21307714", "http://www.ncbi.nlm.nih.gov/pubmed/17303258", "http://www.ncbi.nlm.nih.gov/pubmed/10874640", "http://www.ncbi.nlm.nih.gov/pubmed/20621975", "http://www.ncbi.nlm.nih.gov/pubmed/9130129", "http://www.ncbi.nlm.nih.gov/pubmed/9571278", "http://www.ncbi.nlm.nih.gov/pubmed/20301454", "http://www.ncbi.nlm.nih.gov/pubmed/8929375", "http://www.ncbi.nlm.nih.gov/pubmed/16760737", "http://www.ncbi.nlm.nih.gov/pubmed/15883926", "http://www.ncbi.nlm.nih.gov/pubmed/9508238", "http://www.ncbi.nlm.nih.gov/pubmed/17979970", "http://www.ncbi.nlm.nih.gov/pubmed/7605558", "http://www.ncbi.nlm.nih.gov/pubmed/15884042", "http://www.ncbi.nlm.nih.gov/pubmed/16970241" ], "ideal_answer": [ "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis and marfanoid habitus.", "Hirschsprung disease is very often identified as an additional feature of the Goldberg-Shprintzen syndrome.", "Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndromeMutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Goldberg-Shprintzen syndrome (GSS) in humans.", "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.\nThe Shprintzen-Goldberg syndrome is an extremely rare syndrome with a characteristic face. This is one of a group of disorders characterized by craniosynostosis and marfanoid features." ], "exact_answer": [ "Craniosynostosis" ], "type": "factoid", "id": "5519110f622b19434500000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Goldberg-Shprintzen syndrome (GOSHS, MIM #609460) is an autosomal recessive disorder of intellectual disability, specific facial gestalt and Hirschsprung's disease (HSCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Goldberg-Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20621975", "endSection": "abstract" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1400, "text": "Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20621975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Mutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Goldberg-Shprintzen syndrome (GSS) in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18192286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "We describe a brother and sister with Hirschsprung disease, hypotonia, and ptosis. Their condition resembles that in 2 sibs reported by Goldberg and Shprintzen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1785632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "A 5-year-old girl with Hirschsprung disease, unusual facial appearance, psychomotor retardation, epilepsy, and congenital heart disease is reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7605558", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 487, "text": "Cranial computed tomography demonstrated abnormal findings that may suggest defective neuronal migration and/or dysgenesis of the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7605558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "In 1981, Goldberg and Shprintzen described siblings with short-segment Hirschsprung disease, cleft palate, microcephaly, mild mental retardation, short stature and distinctive facial appearance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9571278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10874640", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10874640", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 402, "text": "The patient showed dysmorphic facies and weakness of connective tissue, and was scheduled to undergo abdominal surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23984569", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 558, "text": "Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23023332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "We report on maternal half-sibs born to unaffected, non-consanguineous parents with classical Shprintzen-Goldberg syndrome (SGS) who had in addition intestinal malrotation and an aberrant subclavian artery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22639450", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 441, "text": "keletal abnormalities common to 3 of them include bowing of long bones (with a variable degree of progression over time), flare of the metaphyses, a large anterior fontanel with persistent patency into the second to fourth years of life, 13 pairs of ribs, distinct vertebral abnormalities which were absent neonatally but evolved by the second year of life, and progressive osteopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7573130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Marfanoid phenotype with craniosynostosis (Shprintzen-Goldberg syndrome) is a rare disorder previously described in only 5 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7573131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8563763", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 503, "text": "Additional common findings include other craniofacial anomalies, hypotonia, obstructive apnea, foot deformity, and congenital weakness of the abdominal wall", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8563763", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 372, "text": " The radiological features were characterized by late-onset craniosynostosis, arachnodactyly, undermodeling of short tubular bones, mildly undermodeled and slightly bowed long bones, twisted ribs and tall vertebral bodies with elongated neural arches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8929375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Aortic root replacement for annuloaortic ectasia in Shprintzen-Goldberg syndrome: a case report", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9130129", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Annuloaortic ectasia due to Shprintzen-Goldberg syndrome (SGS) is reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9130129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Shprintzen-Goldberg syndrome is one of a group of disorders characterized by craniosynostosis and marfanoid habitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9508238", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 195, "text": "The Shprintzen-Goldberg syndrome is an extremely rare syndrome with a characteristic face. This is one of a group of disorders characterized by craniosynostosis and marfanoid features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12846610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The Shprintzen-Goldberg syndrome (SGS) is a disorder of unknown cause comprising craniosynostosis, a marfanoid habitus and skeletal, neurological, cardiovascular, and connective-tissue anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15884042", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 913, "text": "Other commonly reported manifestations include hypotonia in at least the neonatal period, developmental delay, and inguinal or umbilical hernia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15884042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Shprintzen-Goldberg syndrome is a rare connective tissue disorder characterized by marfanoid habitus and additional dysmorphic stigmata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16970241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Overall intelligibility, language, articulation, voice and resonance characteristics in a child with Shprintzen-Goldberg syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17303258", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Shprintzen-Goldberg syndrome (SGS) is a rare disorder characterized by a Marfan-like habitus, mental retardation and craniosynostosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17979970", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 802, "text": "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Surgical treatment for scoliosis in patients with Shprintzen-Goldberg syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21307714", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 106, "text": "Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis and marfanoid habitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21307714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "We identified, by homozygosity mapping, a novel locus on 10q21.3-q22.1 for Goldberg-Shprintzen syndrome (GOSHS) in a consanguineous Moroccan family. Phenotypic features of GOSHS in this inbred family included microcephaly and mental retardation, which are both central nervous system defects, as well as Hirschsprung disease, an enteric nervous system defect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15883926", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 839, "text": "We demonstrate that homozygous nonsense mutations in KIAA1279 at 10q22.1, encoding a protein with two tetratrico peptide repeats, underlie this syndromic form of Hirschsprung disease and generalized polymicrogyria, establishing the importance of KIAA1279 in both enteric and central nervous system development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15883926", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 991, "text": "We report on four children in whom was diagnosed a neurocristopathy, associating Hirschsprung's disease with a wide spectrum of neurologic abnormalities. The patients included two children presenting the phenotypic features of the Goldberg-Shprintzen syndrome: distinct dysmorphic facial features, microcephaly, and mental retardation, along with agenesis of the corpus callosum and cortical malformations associated with intractable seizures in one child. The third newborn presented with the Haddad syndrome: short-segment Hirschsprung's disease associated with the congenital central hypoventilation syndrome requiring permanent artificial ventilation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12878302", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1394, "text": "Therefore, awareness of a possible neurocristopathy associated with neurologic abnormalities should be taken into account in any patient newly diagnosed with Hirschsprung's disease to detect the abnormalities early and promptly manage them", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12878302", "endSection": "abstract" } ] }, { "body": "Which protein is causing Netherton syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23344365", "http://www.ncbi.nlm.nih.gov/pubmed/24015757", "http://www.ncbi.nlm.nih.gov/pubmed/24292773", "http://www.ncbi.nlm.nih.gov/pubmed/21697885", "http://www.ncbi.nlm.nih.gov/pubmed/21895535", "http://www.ncbi.nlm.nih.gov/pubmed/24138501", "http://www.ncbi.nlm.nih.gov/pubmed/23347305", "http://www.ncbi.nlm.nih.gov/pubmed/23407075", "http://www.ncbi.nlm.nih.gov/pubmed/24211642", "http://www.ncbi.nlm.nih.gov/pubmed/20657595" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3345", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/SPINK5" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/SPINK5", "o": "http://www.dbpedia.org/resource/SPINK5" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/SPINK5", "o": "SPINK5" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3345", "o": "Netherton syndrome, 256500" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3345", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/LEKTI" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/LEKTI", "o": "LEKTI" } ], "ideal_answer": [ "Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor)" ], "exact_answer": [ "LEKTI", "lymphoepithelial Kazal type-related inhibitor" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056770", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:0050474", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "factoid", "id": "54ff45966ad7dcbc12000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Netherton syndrome (NTS) is a rare genetic skin disease caused by mutations in the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho-epithelial Kazal-type-related inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Netherton syndrome is caused by loss-of-function mutations in SPINK5 encoding the Kazal-type inhibitor LEKTI-1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211642", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 252, "text": "Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138501", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 308, "text": "Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24015757", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 502, "text": "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407075", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 879, "text": "syndrome and caused by a genetic mutation in SPINK5, may be a facilitating factor for the infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23347305", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 382, "text": "NS is caused by loss-of-function mutations in SPINK5 (serine protease inhibitor of kazal type 5) encoding LEKTI-1 (lympho-epithelial kazal type related inhibitor type 5) expressed in stratified epithelia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23344365", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 445, "text": "Netherton syndrome, which arises due to mutations in serine protease inhibitor Kazal-type 5 (SPINK5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21895535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is the defective protein of the ichthyosiform condition Netherton syndrome (NS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Deficiency in the serine protease inhibitor LEKTI is the etiological origin of Netherton syndrome, which causes detachment of the stratum corneum and chronic inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20657595", "endSection": "abstract" } ] }, { "body": "Mutations in which gene and which protein are associated with Netherton syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22377713", "http://www.ncbi.nlm.nih.gov/pubmed/17608759", "http://www.ncbi.nlm.nih.gov/pubmed/10835624", "http://www.ncbi.nlm.nih.gov/pubmed/19438860", "http://www.ncbi.nlm.nih.gov/pubmed/11841556", "http://www.ncbi.nlm.nih.gov/pubmed/16307658", "http://www.ncbi.nlm.nih.gov/pubmed/20877344", "http://www.ncbi.nlm.nih.gov/pubmed/17989726", "http://www.ncbi.nlm.nih.gov/pubmed/21251800", "http://www.ncbi.nlm.nih.gov/pubmed/11511292", "http://www.ncbi.nlm.nih.gov/pubmed/21255986", "http://www.ncbi.nlm.nih.gov/pubmed/23407075", "http://www.ncbi.nlm.nih.gov/pubmed/15304086", "http://www.ncbi.nlm.nih.gov/pubmed/16225619", "http://www.ncbi.nlm.nih.gov/pubmed/24015757", "http://www.ncbi.nlm.nih.gov/pubmed/16796630" ], "ideal_answer": [ "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues." ], "exact_answer": [ [ "SPINK5 gene" ], [ "LEKTI protein" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056770" ], "type": "list", "id": "56f56a8609dd18d46b00000b", "snippets": [ { "offsetInBeginSection": 323, "offsetInEndSection": 502, "text": "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407075", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 489, "text": "Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11841556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Netherton syndrome (NS) is a rare, life-threatening ichthyosiform syndrome caused by recessive loss-of-function mutations in SPINK5 gene encoding lymphoepithelial Kazal-type-related inhibitor (LEKTI), a serine protease inhibitor expressed in the most differentiated epidermal layers and crucial for skin barrier function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22377713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Netherton syndrome (NS) is a debilitating congenital skin disorder caused by mutations in the SPINK5 gene encoding the lymphoepithelial Kazal-type-related inhibitor (LEKTI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20877344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Loss-of-function mutations in the Kazal-type serine protease inhibitor, LEKTI, encoded by the SPINK5 gene cause the rare autosomal recessive skin disease Netherton syndrome (NS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19438860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15304086", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Netherton's syndrome is a rare autosomal recessive disorder caused by mutations of the SPINK5 gene, which encodes the lymphoepithelial Kazal-type-related inhibitor (LEKTI) protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17608759", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 462, "text": "We observed microstructural changes and detected LEKTI activity and SPINK5 gene mutation in three Chinese patients with Netherton's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17608759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Several skin diseases and atopic disorders including Netherton syndrome and atopic dermatitis have been associated with mutations and deviations of expression of SPINK5, the gene encoding the human 15-domain serine proteinase inhibitor LEKTI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16307658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Loss-of-function mutations in the Kazal-type serine protease inhibitor, LEKTI, encoded by the SPINK5 gene cause the rare autosomal recessive skin disease Netherton syndrome (NS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19438860", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 309, "text": "Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24015757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": " Netherton syndrome is a severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11841556", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 577, "text": "Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome. Here we describe the intron-exon organization of the gene and characterize the SPINK5 mutations in patients from 21 families of different geographic origin, using denaturing high performance liquid chromatography and direct sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11841556", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 687, "text": "Mutation of the SPINK5 gene has been identified as disease-causing in Netherton syndrome, but the pathophysiology still remains unclear. Almost all SPINK5 mutations result in the absence of the serine-protease inhibitor LEKTI protein in both keratinocytes and lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21255986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Several skin diseases and atopic disorders including Netherton syndrome and atopic dermatitis have been associated with mutations and deviations of expression of SPINK5, the gene encoding the human 15-domain serine proteinase inhibitor LEKTI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16307658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Netherton's syndrome is a rare autosomal recessive disorder caused by mutations of the SPINK5 gene, which encodes the lymphoepithelial Kazal-type-related inhibitor (LEKTI) protein. We observed microstructural changes and detected LEKTI activity and SPINK5 gene mutation in three Chinese patients with Netherton's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17608759", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 799, "text": "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues. Following the identification of the NS causative gene and protein, specific diagnostic tools have been developed, thus breaking up the challenge of distinguishing NS from other congenital ichthyoses with overlapping features, and from severe, early-onset forms of atopic dermatitis or psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407075", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 341, "text": "Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11841556", "endSection": "abstract" } ] }, { "body": "Which disease of the central nervous system is characterized by the presence of Lewy bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2085926", "http://www.ncbi.nlm.nih.gov/pubmed/22355263", "http://www.ncbi.nlm.nih.gov/pubmed/22251432", "http://www.ncbi.nlm.nih.gov/pubmed/25514659", "http://www.ncbi.nlm.nih.gov/pubmed/23281786", "http://www.ncbi.nlm.nih.gov/pubmed/23979994", "http://www.ncbi.nlm.nih.gov/pubmed/23587141", "http://www.ncbi.nlm.nih.gov/pubmed/24465140", "http://www.ncbi.nlm.nih.gov/pubmed/10986355", "http://www.ncbi.nlm.nih.gov/pubmed/23225525", "http://www.ncbi.nlm.nih.gov/pubmed/24291999", "http://www.ncbi.nlm.nih.gov/pubmed/19877240", "http://www.ncbi.nlm.nih.gov/pubmed/20174468", "http://www.ncbi.nlm.nih.gov/pubmed/19155272", "http://www.ncbi.nlm.nih.gov/pubmed/23531432", "http://www.ncbi.nlm.nih.gov/pubmed/1534893", "http://www.ncbi.nlm.nih.gov/pubmed/24095115" ], "ideal_answer": [ "Parkinson s disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar \u03b1-synuclein ", "Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar \u03b1-synuclein.", "Parkinsons disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The protein \u03b1-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites" ], "exact_answer": [ "Parkinson's disease (PD)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002490", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002493", "http://www.disease-ontology.org/api/metadata/DOID:331" ], "type": "factoid", "id": "550c3754a103b78016000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar \u03b1-synuclein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23979994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Parkinson's disease is characterized by \u03b1-synuclein pathology in the form of Lewy bodies and Lewy neurites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Parkinson's disease is characterized by neuronal death in the substantia nigra and the presence of intracellular inclusions of \u03b1-synuclein in the Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Parkinson's disease, also known as paralysis agitans, is a progressive degenerative disorder of the central nervous system, with onset usually between the ages of 50 and 65 years, and is associated with loss of dopaminergic neurons in the subsantia nigra and the presence of Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281786", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1118, "text": "The protein \u03b1-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23225525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Parkinson's disease (PD) and related Lewy body diseases are characterized by deposition of \u03b1-synuclein aggregates in both the central nervous system and peripheral nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24465140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Parkinsons disease (PD) and dementia with Lewy bodies are common disorders of the aging population and characterized by the progressive accumulation of \ufffd-synuclein (\ufffd-syn) in the central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22251432", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 343, "text": "AF-LB and Parkinsons disease (PD) share the neuropathological findings characterized by widely distributed Lewy bodies in the central nervous system including the substantia nigra and locus coeruleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2085926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Parkinsons disease (PD) and dementia with Lewy bodies (DLB) are characterized by abnormal deposition of \ufffd-synuclein aggregates in many regions of the central and peripheral nervous systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22355263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "A number of neurodegenerative diseases including Parkinsons disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19155272", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 452, "text": "They have been a long time the hallmark of Parkinsons disease, but in recent years it has emerged that a small group of rare disorders or rare variants of common degenerative diseases are also sometimes associated with Lewy bodies in the nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1534893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "BACKGROUND: Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by alpha-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinsons Disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20174468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Although Parkinsons disease with later dementia (PDD) and dementia with Lewy bodies (DLB) are pathologically characterized by the presence of intraneuronal Lewy inclusion bodies, amyloid deposition is also associated to varying degrees with both these disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19877240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Parkinsons disease (PD) is a neurodegnerative disorder that is pathologically characterized by the presence of Lewy bodies in the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10986355", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 962, "text": "However, it seems that Braak staging can not explain difference in severity of autonomic failure between DLB and PD. As a possibility, in DLB patients with significant autonomic failure, Lewy bodies may have been localized to the peripheral autonomic nervous system in a long time before onset of dementia or parkinsonism, and propagation of Lewy bodies into the central nervous system may be initiated by apparition of certain promotion factor, such as ageing and amyloid-\ufffd.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514659", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 942, "text": "These include multiple system atrophy (MSA), characterized by accumulation of glial cytoplasmic inclusions, and Lewy body disorders, including Parkinson disease (PD), dementia with Lewy bodies, and the so-called \"pure\" autonomic failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24095115", "endSection": "abstract" } ] }, { "body": "Which deiodinase is known to be present in liver?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9389494", "http://www.ncbi.nlm.nih.gov/pubmed/9794474", "http://www.ncbi.nlm.nih.gov/pubmed/8550759", "http://www.ncbi.nlm.nih.gov/pubmed/9709961", "http://www.ncbi.nlm.nih.gov/pubmed/7629231", "http://www.ncbi.nlm.nih.gov/pubmed/15072569" ], "ideal_answer": [ "High D1 and D3 activities are present in fetal human liver, and high D1 and mostly absent D3 activities are present in adult human liver." ], "exact_answer": [ "Type 1 deiodinase", "type 3 deiodinase" ], "type": "factoid", "id": "517a8b768ed59a060a00003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15072569", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "In embryonic chicken liver (ECL) two types of iodothyronine deiodinases are expressed: D1 and D3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9389494", "endSection": "sections.0" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1666, "text": "In liver homogenates, D1 activity was not correlated with age, whereas D3 activity showed a strong negative correlation with age (r -0.84), with high D3 activities in preterm infants and (except in 1 infant of 35 weeks) absent D3 activity in full-term infants. In microsomes, D1 activities amounted to 4.3-60 pmol/min/mg protein in fetal livers and to 170-313 pmol/min/mg protein in adult livers, whereas microsomal D3 activities were 0.15-1.45 pmol/min/mg protein in fetuses and <0.1 pmol/min/mg protein in all but one adult.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9709961", "endSection": "sections.0" }, { "offsetInBeginSection": 1822, "offsetInEndSection": 1935, "text": "high D1 and D3 activities in fetal human liver, and high D1 and mostly absent D3 activities in adult human liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9709961", "endSection": "sections.0" } ] }, { "body": "Which proteins participate in the formation of the Notch transcriptional activation complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20972443", "http://www.ncbi.nlm.nih.gov/pubmed/18758478", "http://www.ncbi.nlm.nih.gov/pubmed/11536431", "http://www.ncbi.nlm.nih.gov/pubmed/20118921", "http://www.ncbi.nlm.nih.gov/pubmed/21124806", "http://www.ncbi.nlm.nih.gov/pubmed/12644465", "http://www.ncbi.nlm.nih.gov/pubmed/12205678", "http://www.ncbi.nlm.nih.gov/pubmed/21245387", "http://www.ncbi.nlm.nih.gov/pubmed/16530044", "http://www.ncbi.nlm.nih.gov/pubmed/22325781" ], "ideal_answer": [ "The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML). ICN binds to a highly conserved DNA-binding transcription factor called CSL (also known as RBP-Jkappa, CBF1, Suppressor of Hairless, and Lag-1) and recruits Mastermind-like transcriptional co-activators to form a transcriptional activation complex.", "Although it is well understood that N(ICD) forms a transcriptional activation complex, little is known about how the complex is assembled. The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML)." ], "exact_answer": [ [ "Notch intracellular domain (NICD)", "NICD", "Intracellular part of Notch", "ICN", "NIC" ], [ "Transcription factor CSL", "RBP-Jkappa", "CBF1", "Suppressor of Hairless", "Lag-1" ], [ "The coactivator protein Mastermind-like 1", "MAML-1" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015533", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051880" ], "type": "list", "id": "54fb6fb5d176fff445000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML). The \"RAM\" region of NICD recruits Notch to CSL, facilitating the binding of MAML at the interface between the ankyrin (ANK) repeat domain of NICD and CSL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22325781", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 623, "text": "Inappropriate release of the intracellular domain of Notch (N(ICD)) from the plasma membrane results in the accumulation of deregulated nuclear N(ICD) that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear N(ICD) forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21245387", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 762, "text": "Although it is well understood that N(ICD) forms a transcriptional activation complex, little is known about how the complex is assembled.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21245387", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 640, "text": "Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21124806", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 414, "text": "We report here the crystal structure of a Notch transcriptional activation complex containing the ankyrin domain of human Notch1 (ANK), the transcription factor CSL on cognate DNA, and a polypeptide from the coactivator Mastermind-like-1 (MAML-1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16530044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "Ligand binding by Notch receptors triggers a series of proteolytic cleavages that liberate the intracellular portion of Notch (ICN) from the cell membrane, permitting it to translocate to the nucleus. Nuclear ICN binds to a highly conserved DNA-binding transcription factor called CSL (also known as RBP-Jkappa, CBF1, Suppressor of Hairless, and Lag-1) and recruits Mastermind-like transcriptional co-activators to form a transcriptional activation complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12644465", "endSection": "abstract" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1709, "text": "On the basis of our results, we present a working structural model for the organization of the MAML1.ICN.CSL.DNA complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12644465", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1587, "text": "The requirement for cooperative assembly of the MAML1.ICN.CSL.DNA complex suggests that a primary function of ICN is to render CSL competent for MAML loading.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12644465", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 642, "text": "We report here that the astrogliogenic role of Notch is in part mediated by direct binding of the Notch intracellular domain to the CSL DNA binding protein, forming a transcriptional activation complex onto the astrocyte marker gene, glial fibrillary acidic protein (GFAP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12205678", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1103, "text": "Importantly, although the classical CSL-dependent Notch signaling pathway is intact and able to activate the Notch canonical target promoter during the neurogenic phase, it is unable to activate the GFAP promoter during neurogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12205678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Mastermind (Mam) is a component of Notch pathway signaling. In combination with the intracellular domain of Notch and Suppressor of Hairless, Mam forms a transcriptional activation complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11536431", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 564, "text": "High levels of Notch-mediated transcriptional activation require the formation of a ternary complex consisting of NotchICD, CSL (CBF-1, suppressor of hairless, LAG-1) and a Mastermind family member.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20118921", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 353, "text": "This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20972443", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 352, "text": "This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20972443", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 563, "text": "High levels of Notch-mediated transcriptional activation require the formation of a ternary complex consisting of NotchICD, CSL (CBF-1, suppressor of hairless, LAG-1) and a Mastermind family member", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20118921", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 638, "text": "NotchIC, together with the transcriptional coactivator Mastermind, form a ternary complex with CSL that activates transcription from genes that are responsive to Notch signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18758478", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 622, "text": "Nuclear N(ICD) forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21245387", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 456, "text": "Nuclear ICN binds to a highly conserved DNA-binding transcription factor called CSL (also known as RBP-Jkappa, CBF1, Suppressor of Hairless, and Lag-1) and recruits Mastermind-like transcriptional co-activators to form a transcriptional activation complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12644465", "endSection": "abstract" } ] }, { "body": "How is the sequence variability defined in antibodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12072528", "http://www.ncbi.nlm.nih.gov/pubmed/20421997", "http://www.ncbi.nlm.nih.gov/pubmed/9783696", "http://www.ncbi.nlm.nih.gov/pubmed/11292724", "http://www.ncbi.nlm.nih.gov/pubmed/22661385", "http://www.ncbi.nlm.nih.gov/pubmed/17258731", "http://www.ncbi.nlm.nih.gov/pubmed/22863657", "http://www.ncbi.nlm.nih.gov/pubmed/22067045", "http://www.ncbi.nlm.nih.gov/pubmed/12547627", "http://www.ncbi.nlm.nih.gov/pubmed/18721481", "http://www.ncbi.nlm.nih.gov/pubmed/11790764", "http://www.ncbi.nlm.nih.gov/pubmed/8944774", "http://www.ncbi.nlm.nih.gov/pubmed/16609350", "http://www.ncbi.nlm.nih.gov/pubmed/7511773", "http://www.ncbi.nlm.nih.gov/pubmed/16517887", "http://www.ncbi.nlm.nih.gov/pubmed/17353288", "http://www.ncbi.nlm.nih.gov/pubmed/15613860" ], "ideal_answer": [ "The variability at each position of the polypeptide chain is defined as:\nVariability = number of different amino acids at a given position / frequency of the most common amino acid at given position." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000917", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057127", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000940", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906" ], "type": "summary", "id": "532ad4b4d6d3ac6a34000012", "snippets": [ { "offsetInBeginSection": 221, "offsetInEndSection": 399, "text": "Structural and immunochemical data suggest, however, that V3 contains conserved elements which explain its role in binding to virus co-receptors despite its sequence variability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20421997", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 711, "text": "This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates involving a total of 976 Vpr sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18721481", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 1084, "text": "We investigated the possible link between enzyme secretion and variability in the linker sequence segment using site-directed mutagenesis and linker domain swapping to construct mutated and chimeric forms of the IgA1 protease from", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17353288", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 457, "text": "We have performed low to high resolution molecular typing to assess the genetic variability of major histocompatibility complex loci (HLA-A, -B, -Cw, -DRB1, and -DQA1) in a large population of European American patients with IIM (n = 571) representing the major myositis autoantibody groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16609350", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 518, "text": "In this study, we analyzed the value of IHC versus that of microsatellite instability (MSI) testing in predicting mutation status of the MLH1, MSH2, and MSH6 genes in colorectal carcinomas and adenomas, and explored the frequency and significance of immunohistochemical staining variability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15613860", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 1004, "text": "Computational analyses were used to position the epitope in the context of the virion-associated envelope glycoprotein complex, to determine the variability of the surrounding surface, and to calculate the surface accessibility of possible glycan- and polypeptide-epitope components. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12072528", "endSection": "abstract" }, { "offsetInBeginSection": 1541, "offsetInEndSection": 1847, "text": "ese variations in structure of an expression site for a major, immunoprotective outer membrane protein have important implications for vaccine development and for obtaining an improved understanding of the mechanisms of persistence of ehrlichial infections in humans, domestic animals, and reservoir hosts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11292724", "endSection": "abstract" }, { "offsetInBeginSection": 930, "offsetInEndSection": 1127, "text": " The V3 region of the isolates used in the neutralization assay was amplified by PCR, directly sequenced, and analyzed to reveal variability between the consensus HIV-1 sequences and the isolates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9783696", "endSection": "abstract" } ] }, { "body": "Is the transcriptional regulator BACH1 an activator or a repressor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23738048", "http://www.ncbi.nlm.nih.gov/pubmed/23181164", "http://www.ncbi.nlm.nih.gov/pubmed/17257585", "http://www.ncbi.nlm.nih.gov/pubmed/12511571", "http://www.ncbi.nlm.nih.gov/pubmed/15809329", "http://www.ncbi.nlm.nih.gov/pubmed/18426999", "http://www.ncbi.nlm.nih.gov/pubmed/23562577", "http://www.ncbi.nlm.nih.gov/pubmed/14660636", "http://www.ncbi.nlm.nih.gov/pubmed/24035498", "http://www.ncbi.nlm.nih.gov/pubmed/15613547", "http://www.ncbi.nlm.nih.gov/pubmed/19439223", "http://www.ncbi.nlm.nih.gov/pubmed/19011633", "http://www.ncbi.nlm.nih.gov/pubmed/17701549", "http://www.ncbi.nlm.nih.gov/pubmed/16824198", "http://www.ncbi.nlm.nih.gov/pubmed/20127796", "http://www.ncbi.nlm.nih.gov/pubmed/11387216", "http://www.ncbi.nlm.nih.gov/pubmed/22698995", "http://www.ncbi.nlm.nih.gov/pubmed/18555605", "http://www.ncbi.nlm.nih.gov/pubmed/11530014", "http://www.ncbi.nlm.nih.gov/pubmed/19282658", "http://www.ncbi.nlm.nih.gov/pubmed/18325350", "http://www.ncbi.nlm.nih.gov/pubmed/20388958", "http://www.ncbi.nlm.nih.gov/pubmed/15464985", "http://www.ncbi.nlm.nih.gov/pubmed/16530877", "http://www.ncbi.nlm.nih.gov/pubmed/23880309", "http://www.ncbi.nlm.nih.gov/pubmed/16724942", "http://www.ncbi.nlm.nih.gov/pubmed/20501657", "http://www.ncbi.nlm.nih.gov/pubmed/16487043", "http://www.ncbi.nlm.nih.gov/pubmed/18948842", "http://www.ncbi.nlm.nih.gov/pubmed/21555518", "http://www.ncbi.nlm.nih.gov/pubmed/20345481", "http://www.ncbi.nlm.nih.gov/pubmed/19035757", "http://www.ncbi.nlm.nih.gov/pubmed/18550526", "http://www.ncbi.nlm.nih.gov/pubmed/16894358", "http://www.ncbi.nlm.nih.gov/pubmed/23446334", "http://www.ncbi.nlm.nih.gov/pubmed/15743416", "http://www.ncbi.nlm.nih.gov/pubmed/22127667", "http://www.ncbi.nlm.nih.gov/pubmed/17682061", "http://www.ncbi.nlm.nih.gov/pubmed/19119918", "http://www.ncbi.nlm.nih.gov/pubmed/17901053", "http://www.ncbi.nlm.nih.gov/pubmed/21473739", "http://www.ncbi.nlm.nih.gov/pubmed/22847612", "http://www.ncbi.nlm.nih.gov/pubmed/17942419", "http://www.ncbi.nlm.nih.gov/pubmed/22289179", "http://www.ncbi.nlm.nih.gov/pubmed/21982894", "http://www.ncbi.nlm.nih.gov/pubmed/14580148", "http://www.ncbi.nlm.nih.gov/pubmed/22107958", "http://www.ncbi.nlm.nih.gov/pubmed/15855052", "http://www.ncbi.nlm.nih.gov/pubmed/22735309", "http://www.ncbi.nlm.nih.gov/pubmed/15068251", "http://www.ncbi.nlm.nih.gov/pubmed/21373270", "http://www.ncbi.nlm.nih.gov/pubmed/21812759", "http://www.ncbi.nlm.nih.gov/pubmed/15734732", "http://www.ncbi.nlm.nih.gov/pubmed/14504288", "http://www.ncbi.nlm.nih.gov/pubmed/19591297", "http://www.ncbi.nlm.nih.gov/pubmed/16771696", "http://www.ncbi.nlm.nih.gov/pubmed/15175654", "http://www.ncbi.nlm.nih.gov/pubmed/19897490", "http://www.ncbi.nlm.nih.gov/pubmed/12356737" ], "triples": [ { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/P97302", "o": "http://purl.uniprot.org/keywords/678" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5039373330320012", "o": "BTB and CNC homolog 1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5039373330320011", "o": "Transcription regulator protein BACH1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P97302", "o": "http://linkedlifedata.com/resource/#_5039373330320011" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/P97302", "o": "http://linkedlifedata.com/resource/#_5039373330320012" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/678", "o": "Repressor" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/O14867", "o": "http://purl.uniprot.org/keywords/678" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/O14867", "o": "http://linkedlifedata.com/resource/#_4F3134383637001F" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-1263541", "o": "BACH1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/O14867", "o": "http://linkedlifedata.com/resource/#_4F3134383637001D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3134383637001D", "o": "Transcription regulator protein BACH1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3134383637001E", "o": "BTB and CNC homolog 1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3134383637001F", "o": "HA2303" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/intact/EBI-1263541", "o": "http://purl.uniprot.org/uniprot/O14867" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/O14867", "o": "http://linkedlifedata.com/resource/#_4F3134383637001E" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/P97302", "o": "http://purl.uniprot.org/keywords/10" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/10", "o": "Activator" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/10", "o": "Positive activator" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/O14867", "o": "http://purl.uniprot.org/go/0003700" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0003700", "o": "http://www.geneontology.org/go#GO:0003700" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0003700", "o": "sequence-specific DNA binding transcription factor activity" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasMolecularFunction", "s": "http://purl.uniprot.org/uniprot/O14867", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0003700" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0003700", "o": "sequence-specific DNA binding transcription factor activity" } ], "ideal_answer": [ "BACH1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1), a key cytoprotective enzyme that has antioxidant and anti-inflammatory activities. In the absence of elevated intracellular heme or oxidative stress, BACH1 functions as a repressor of the enhancers of heme oxygenase-1 (HO-1) gene (Hmox-1) by forming heterodimers with the small Maf proteins such as MafK. Bach1 is recruited to a subset of p53 target genes and contributes to impeding p53 action by promoting histone deacetylation.", "BACH1 is, in most contexts, a transcriptional repressor" ], "exact_answer": [ "Repressor" ], "concepts": [ "http://www.uniprot.org/uniprot/BACH1_MOUSE", "http://www.uniprot.org/uniprot/FANCJ_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006351", "http://www.uniprot.org/uniprot/CODY_LACLA", "http://www.uniprot.org/uniprot/FANCJ_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050976", "http://www.uniprot.org/uniprot/BACH1_HUMAN" ], "type": "factoid", "id": "52fa6ac72059c6d71c000055", "snippets": [ { "offsetInBeginSection": 948, "offsetInEndSection": 995, "text": "the impact of BACH1 repression on transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21555518", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 268, "text": "Bach1 is a repressor of the oxidative stress response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20501657", "endSection": "abstract" }, { "offsetInBeginSection": 2113, "offsetInEndSection": 2147, "text": "transcriptional repressor Bach-1, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23562577", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 475, "text": "Bach1, a transcriptional repressor of the HMOX1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22698995", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 315, "text": "The mechanism underlying Bach1-mediated HO-1 repression is less well understood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22107958", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 905, "text": "Transcription factor BACH1 [BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1] binds to ARE-like sequences, functioning as a transcriptional repressor ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21812759", "endSection": "abstract" }, { "offsetInBeginSection": 23, "offsetInEndSection": 87, "text": "Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20388958", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 437, "text": " its regulatory mechanism by the transcriptional repressor, BTB and CNC homology 1 (Bach1),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20345481", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 201, "text": "Bach1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20127796", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 295, "text": "Bach1, the negative regulator of Nrf2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19897490", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 72, "text": "ach1 is a transcriptional repressor of the heme oxygenase (HO)-1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19439223", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1668, "text": "The inhibitory role for Bach1 may stem from its activity to repress gene expression including HO-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19282658", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 290, "text": "Bach1 is a transcriptional repressor of the HO-1 gene (Hmox-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19119918", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 413, "text": "Here we show that the transcription factor Bach1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1), which inhibits oxidative stress-inducible genes, is a crucial negative regulator of oxidative stress-induced cellular senescence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011633", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 427, "text": "Bach1 is a transcriptional repressor of the HO-1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18555605", "endSection": "abstract" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1645, "text": "Bach1 repressively controls myocardial HO-1 expression ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18426999", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 263, "text": " the transcriptional repressor BACH1 binds ARE-like enhancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942419", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 123, "text": " transcription factor Bach1 functions as a repressor of the enhancers of heme oxygenase-1 (HO-1) gene (Hmox-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17701549", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 297, "text": "Bach1, a transcription factor that suppresses the HO-1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17257585", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 742, "text": "Bach1, a transcriptional repressor that is negatively regulated by heme in mammalian cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16894358", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1184, "text": "Bach1 normally represses HO-1 expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16724942", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 300, "text": "Bach1, a heme binding protein that represses gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16530877", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1137, "text": "complexes with Bach1 repress MARE-dependent gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16487043", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 55, "text": "transcriptional repressor Bach1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15855052", "endSection": "title" }, { "offsetInBeginSection": 469, "offsetInEndSection": 525, "text": "bach1-ablation resulted in increased expression of HO-1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15743416", "endSection": "abstract" }, { "offsetInBeginSection": 1478, "offsetInEndSection": 1541, "text": "Bach1 contributes to the down-regulation of ARE-regulated genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15734732", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1458, "text": "evidence that BACH1 acts as a transcriptional repressor in the regulation of MARE-dependent genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15613547", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 150, "text": "Bach1 forms a heterodimer with small Maf family, and functions as a repressor of the Maf recognition element (MARE) in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15464985", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 79, "text": "ach1 is a transcriptional repressor of heme oxygenase-1 and beta-globin genes,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15175654", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1494, "text": "BACH1 suppresses expression of HO1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15068251", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 138, "text": "transcription factor Bach1 heterodimerizes with small Maf proteins to repress Maf recognition element (MARE)-dependent gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14660636", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 994, "text": " Bach1 as a heme-regulated and hypoxia-inducible repressor for transcription of the HO-1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14580148", "endSection": "abstract" }, { "offsetInBeginSection": 34, "offsetInEndSection": 93, "text": "Bach1, a transcriptional repressor of heme oxygenase-1 gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14504288", "endSection": "title" }, { "offsetInBeginSection": 570, "offsetInEndSection": 619, "text": "Bach1, a heme-regulated transcriptional repressor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12511571", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 313, "text": "a heme-binding factor, Bach1, is a critical physiological repressor of ho-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12356737", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 109, "text": "transcription repressor Bach1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11387216", "endSection": "title" } ] }, { "body": "Is Kanzaki disease associated with deficiency in alpha-N-acetylgalactosaminidase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11251574", "http://www.ncbi.nlm.nih.gov/pubmed/14685826", "http://www.ncbi.nlm.nih.gov/pubmed/19683538", "http://www.ncbi.nlm.nih.gov/pubmed/8577046", "http://www.ncbi.nlm.nih.gov/pubmed/15136691", "http://www.ncbi.nlm.nih.gov/pubmed/15619430" ], "ideal_answer": [ "Yes, Kanzaki disease is attributable to a deficiency in alpha-N-acetylgalactosaminidase, which hydrolyzes GalNAcalpha1-O-Ser/Thr." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/NAGAB_CHICK", "http://www.uniprot.org/uniprot/NAGAB_BOSIN", "http://www.uniprot.org/uniprot/NAGAB_RAT", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048809", "http://www.uniprot.org/uniprot/G1092_BACFN", "http://www.uniprot.org/uniprot/GH109_ELIME", "http://www.uniprot.org/uniprot/GH109_SHEON", "http://www.uniprot.org/uniprot/NAGAB_HUMAN" ], "type": "yesno", "id": "56f7c44109dd18d46b000013", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 178, "text": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1875, "text": " Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685826", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "We describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15136691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11251574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Schindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme, alpha-N-acetylgalactosaminidase (E.C.3.2.1.49).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19683538", "endSection": "title" }, { "offsetInBeginSection": 1920, "offsetInEndSection": 2171, "text": "These data suggest that a prototype of alpha-NAGA deficiency in Kanzaki disease and factors other than the defect of alpha-NAGA may contribute to severe neurological disorders, and Kanzaki disease is thought to be caused by a single enzyme deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11251574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. Missense mutations, R329W or R329Q were identified in two Japanese Kanzaki patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11251574", "endSection": "abstract" } ] }, { "body": "Is Mycobacterium avium less susceptible to antibiotics than Mycobacterium tuberculosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19956964", "http://www.ncbi.nlm.nih.gov/pubmed/12355367", "http://www.ncbi.nlm.nih.gov/pubmed/21258569", "http://www.ncbi.nlm.nih.gov/pubmed/16410940", "http://www.ncbi.nlm.nih.gov/pubmed/17548640", "http://www.ncbi.nlm.nih.gov/pubmed/15328105", "http://www.ncbi.nlm.nih.gov/pubmed/19302308", "http://www.ncbi.nlm.nih.gov/pubmed/15347635", "http://www.ncbi.nlm.nih.gov/pubmed/10988097", "http://www.ncbi.nlm.nih.gov/pubmed/17897062", "http://www.ncbi.nlm.nih.gov/pubmed/1441463", "http://www.ncbi.nlm.nih.gov/pubmed/19119013" ], "ideal_answer": [ "Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome. M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival. Patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count<100.0 cell/mL were investigated. Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare. The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. intracellulare, 0.06/0.5" ], "exact_answer": "yes", "type": "yesno", "id": "5710a650cf1c32585100002b", "snippets": [ { "offsetInBeginSection": 1447, "offsetInEndSection": 1550, "text": "The prevalence of MAC lung infection in two inner city hospitals was four times higher than that of TB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21258569", "endSection": "abstract" }, { "offsetInBeginSection": 1792, "offsetInEndSection": 1908, "text": "Most patients with combined infection were clinically consistent with MTB and responded to anti MTB treatment alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21258569", "endSection": "abstract" }, { "offsetInBeginSection": 1719, "offsetInEndSection": 1868, "text": "The triplex PCR developed by us could be used to detect and differentiate M. tuberculosis, M. avium and other mycobacteria in a single reaction tube.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19302308", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 567, "text": "Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16410940", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 296, "text": "The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15347635", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 627, "text": "The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. intracellulare, 0.06/0.5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15347635", "endSection": "abstract" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1692, "text": "These results suggest that capuramycin analogues exhibit strong antimycobacterial potential and should be considered for further evaluation in the treatment of M. tuberculosis and M. avium-M. intracellulare complex infections in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15347635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12355367", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 694, "text": "Overall incidences of Mycobacterium tuberculosis (TB) and Mycobacterium avium complex (MAC) were 0.8 and 1.4 cases/100 person-years of follow-up (PYF), decreasing from 1.8 (TB) and 3.5 cases/100 PYF (MAC) before September 1995 to 0.3 and 0.2 cases/100 PYF after March 1997.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10988097", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 750, "text": "Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1441463", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1385, "text": "MAC pulmonary disease should be considered in the differential diagnosis of SPNs, even when encountered in geographic regions with a high prevalence of pulmonary tuberculosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19956964", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 400, "text": "From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count<100.0 cell/mL were investigated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16410940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to Mycobacterium avium infection and influences efficacy of antibiotic therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17548640", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19119013", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 364, "text": "Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12355367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19119013", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 179, "text": "a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19119013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19119013", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1214, "text": "tuberculosis appear to have different genetic mechanisms for resisting the effects of these antibiotics, with pks12 playing a relatively more significant role in MAC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15328105", "endSection": "abstract" } ] }, { "body": "What molecule is targeted by suvorexant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22920041", "http://www.ncbi.nlm.nih.gov/pubmed/25489915", "http://www.ncbi.nlm.nih.gov/pubmed/25406050", "http://www.ncbi.nlm.nih.gov/pubmed/25533960", "http://www.ncbi.nlm.nih.gov/pubmed/25667197", "http://www.ncbi.nlm.nih.gov/pubmed/23197752", "http://www.ncbi.nlm.nih.gov/pubmed/24757363", "http://www.ncbi.nlm.nih.gov/pubmed/25397996", "http://www.ncbi.nlm.nih.gov/pubmed/21473737", "http://www.ncbi.nlm.nih.gov/pubmed/26478806" ], "ideal_answer": [ "Suvorexant is a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia." ], "exact_answer": [ "orexin" ], "type": "factoid", "id": "56c1f003ef6e394741000039", "snippets": [ { "offsetInBeginSection": 605, "offsetInEndSection": 773, "text": "Suvorexant is the first DORA to be approved and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26478806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Suvorexant: a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25667197", "endSection": "title" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1329, "text": "CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25667197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533960", "endSection": "title" }, { "offsetInBeginSection": 362, "offsetInEndSection": 594, "text": " The human OX2 receptor (OX2R) belongs to the \u03b2 branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23197752", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21473737", "endSection": "title" }, { "offsetInBeginSection": 588, "offsetInEndSection": 1041, "text": "The neurotransmitter systems on which the development of these agents were based included serotonin for ondansetron and lorcaserin, dopamine for varenicline, substance P (or neurokinin) for aprepitant, melatonin for ramelteon, and orexin for suvorexant. The indications were chemotherapy-induced nausea and vomiting for ondansetron and aprepitant, smoking cessation for varenicline, weight loss for lorcaserin, and insomnia for suvorexant and ramelteon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25406050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Suvorexant, a dual orexin receptor antagonist for the management of insomnia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24757363", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Suvorexant, a dual orexin receptor antagonist for the management of insomnia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24757363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25489915", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 283, "text": "Suvorexant helps in decreasing wakefulness by counteracting orexin activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25397996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": " The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25489915", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 760, "text": "Hypnotic drug development has arguably become more focused in recent years, particularly upon the highly anticipated novel target, the orexin (hypocretin) system. Merck's suvorexant (MK-4305) is the first compound of the so-called dual orexin receptor antagonist (DORA) class expected to be submitted for FDA approval, with a new drug application anticipated in 2012.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22920041", "endSection": "abstract" } ] }, { "body": "For which type of diabetes can empagliflozin be used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "http://www.ncbi.nlm.nih.gov/pubmed/24943000", "http://www.ncbi.nlm.nih.gov/pubmed/26557225", "http://www.ncbi.nlm.nih.gov/pubmed/25692841", "http://www.ncbi.nlm.nih.gov/pubmed/24007456", "http://www.ncbi.nlm.nih.gov/pubmed/22268612", "http://www.ncbi.nlm.nih.gov/pubmed/24186878", "http://www.ncbi.nlm.nih.gov/pubmed/25598831", "http://www.ncbi.nlm.nih.gov/pubmed/24843716", "http://www.ncbi.nlm.nih.gov/pubmed/24746173", "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "http://www.ncbi.nlm.nih.gov/pubmed/25644093", "http://www.ncbi.nlm.nih.gov/pubmed/24795251", "http://www.ncbi.nlm.nih.gov/pubmed/24991224", "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "http://www.ncbi.nlm.nih.gov/pubmed/25941565", "http://www.ncbi.nlm.nih.gov/pubmed/24944269", "http://www.ncbi.nlm.nih.gov/pubmed/23940010", "http://www.ncbi.nlm.nih.gov/pubmed/25332189", "http://www.ncbi.nlm.nih.gov/pubmed/24964723", "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "http://www.ncbi.nlm.nih.gov/pubmed/24948511", "http://www.ncbi.nlm.nih.gov/pubmed/24622369", "http://www.ncbi.nlm.nih.gov/pubmed/23906374", "http://www.ncbi.nlm.nih.gov/pubmed/24463454", "http://www.ncbi.nlm.nih.gov/pubmed/25775379" ], "ideal_answer": [ "The oral antidiabetes agent, empagliflozin, can be used as monotherapy or alongside other glucose-lowering treatments, including insulin, to treat T2DM." ], "exact_answer": [ "type 2 diabetes mellitus" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.disease-ontology.org/api/metadata/DOID:9352" ], "type": "factoid", "id": "571e14fbbb137a4b0c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 257, "text": "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1422, "text": "In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c) and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Empagliflozin: a review of its use in patients with type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "title" }, { "offsetInBeginSection": 1655, "offsetInEndSection": 1774, "text": "This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991224", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "To evaluate the pharmacodynamics, pharmacokinetics, safety and tolerability of empagliflozin in Japanese patients with type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24843716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Pharmacokinetics, pharmacodynamics, safety and tolerability of 4\u00a0weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24843716", "endSection": "title" }, { "offsetInBeginSection": 364, "offsetInEndSection": 481, "text": "We assessed the efficacy and safety of empagliflozin as an add-on treatment in patients with type 2 diabetes and CKD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795251", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 499, "text": "The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24943000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Data from five randomized, placebo-controlled, multiple oral dose studies of empagliflozin in patients with type 2 diabetes mellitus (T2DM; N\u2009=\u2009974; 1-100\u2009mg q.d.; \u226412 weeks) were used to develop a population pharmacokinetic (PK) model for empagliflozin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Empagliflozin, (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol was recently approved by the FDA for the treatment of chronic type 2 diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332189", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 456, "text": "The SGLT2 inhibitor empagliflozin has gained approval in the EU and in the USA for the treatment of adults with T2DM (there is no current indication in type 1 diabetes)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25941565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Pharmacokinetics, pharmacodynamics, safety and tolerability of 4\u00a0weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24843716", "endSection": "title" }, { "offsetInBeginSection": 318, "offsetInEndSection": 513, "text": "The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24943000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23906374", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24944269", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Rationale, design and baseline characteristics of a 4-year (208-week) phase III trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to metformin in patients with type 2 diabetes mellitus with insufficient glycemic control.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24007456", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Exposure-response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24964723", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "With its insulin-independent mechanism of action, empagliflozin monotherapy or combination therapy with other antidiabetic drugs, including insulin, provides a useful addition to the therapeutic options for the management of type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "In several phase III trials (104weeks' duration; typically 24weeks' duration) and extension studies (typically76weeks' treatment), empagliflozin monotherapy or add-on therapy to other antihyperglycaemics, including insulin, improved glycaemic control and reduced bodyweight and systolic blood pressure in adult patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Oral empagliflozin (Jardiance()), a sodium glucose cotransporter-2 (SGLT2) inhibitor, is a convenient once-daily treatment for adult patients with type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 675, "text": "Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of treatment for T2DM that reduce hyperglycemia by reducing renal glucose reabsorption and thereby increasing urinary glucose excretion.This paper reviews the pharmacokinetic and pharmacodynamic properties of the SGLT2 inhibitor empagliflozin , the results of clinical trials investigating the efficacy of empagliflozin given as monotherapy or as add-on therapy on glycemic control, body weight, and blood pressure in patients with T2DM, and the safety and tolerability profile of empagliflozin.Empagliflozin offers good glycemic efficacy, weight loss, blood pressure reduction, and a low risk of hypoglycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Empagliflozin for the treatment of type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "endSection": "title" }, { "offsetInBeginSection": 596, "offsetInEndSection": 955, "text": "This paper reviews the pharmacokinetic and pharmacodynamic properties of the SGLT2 inhibitor empagliflozin , the results of clinical trials investigating the efficacy of empagliflozin given as monotherapy or as add-on therapy on glycemic control, body weight, and blood pressure in patients with T2DM, and the safety and tolerability profile of empagliflozin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "endSection": "abstract" }, { "offsetInBeginSection": 2286, "offsetInEndSection": 2519, "text": "In patients with type 2 diabetes and stage 2 or 3 CKD, empagliflozin reduced HbA1c and was well tolerated. However, our findings might not be applicable to the general population of patients with type 2 diabetes and renal impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795251", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1663, "text": "With its insulin-independent mechanism of action, empagliflozin monotherapy or combination therapy with other antidiabetic drugs, including insulin, provides a useful addition to the therapeutic options for the management of type 2 diabetes. This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 1469, "offsetInEndSection": 1715, "text": "In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo. Empagliflozin was well-tolerated with a favourable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "endSection": "abstract" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1648, "text": "No UTIs or genital infections led to premature discontinuation. In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "endSection": "abstract" }, { "offsetInBeginSection": 1469, "offsetInEndSection": 1648, "text": "In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1155, "text": "In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c) and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991224", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1663, "text": "This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Empagliflozin: a review of its use in patients with type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991224", "endSection": "title" }, { "offsetInBeginSection": 1846, "offsetInEndSection": 2116, "text": "In patients with type 2 diabetes, empagliflozin-induced glycosuria improved \u03b2 cell function and insulin sensitivity, despite the fall in insulin secretion and tissue glucose disposal and the rise in EGP after one dose, thereby lowering fasting and postprandial glycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24463454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus empagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25775379", "endSection": "title" } ] }, { "body": "Which are the main methods for pharmacophore modelling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23651479", "http://www.ncbi.nlm.nih.gov/pubmed/23651482", "http://www.ncbi.nlm.nih.gov/pubmed/16783689", "http://www.ncbi.nlm.nih.gov/pubmed/22650262", "http://www.ncbi.nlm.nih.gov/pubmed/23651486", "http://www.ncbi.nlm.nih.gov/pubmed/23933279", "http://www.ncbi.nlm.nih.gov/pubmed/15807512", "http://www.ncbi.nlm.nih.gov/pubmed/23957390", "http://www.ncbi.nlm.nih.gov/pubmed/24504131", "http://www.ncbi.nlm.nih.gov/pubmed/23862697", "http://www.ncbi.nlm.nih.gov/pubmed/20362693", "http://www.ncbi.nlm.nih.gov/pubmed/22380004", "http://www.ncbi.nlm.nih.gov/pubmed/16996282", "http://www.ncbi.nlm.nih.gov/pubmed/23621564", "http://www.ncbi.nlm.nih.gov/pubmed/18410307", "http://www.ncbi.nlm.nih.gov/pubmed/24266725", "http://www.ncbi.nlm.nih.gov/pubmed/21521148", "http://www.ncbi.nlm.nih.gov/pubmed/21400356", "http://www.ncbi.nlm.nih.gov/pubmed/23334436", "http://www.ncbi.nlm.nih.gov/pubmed/23675939" ], "ideal_answer": [ "A pharmacophore describes the arrangement of molecular features a ligand must contain to efficaciously bind a receptor. Pharmacophore models are developed to improve molecular understanding of ligand\u2013protein interactions, and can be used as a tool to identify novel compounds that fulfil the pharmacophore requirements and have a high probability of being biologically active. Protein structure-based pharmacophores (SBPs) derive these molecular features by conversion of protein properties to reciprocal ligand space. Unlike ligand-based pharmacophore models, which require templates of ligands in their bioactive conformation, SBPs do not depend on ligand information." ], "exact_answer": [ [ "Ligand-based, pharmacophore modeling" ], [ "Structure-base, pharmacophore modeling" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015195", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722" ], "type": "list", "id": "532c0c21d6d3ac6a3400001b", "snippets": [ { "offsetInBeginSection": 8, "offsetInEndSection": 901, "text": "protein interactions are becoming increasingly significant as potential drug targets; however, the rational identification of small molecule inhibitors of such interactions remains a challenge. Pharmacophore modelling is a popular tool for virtual screening of compound libraries, and has previously been successfully applied to the discovery of enzymatic inhibitors. However, the application of pharmacophore modelling in the field of protein:protein interaction inhibitors has historically been considered more of a challenge and remains limited. In this review, we explore the interaction mimicry by known inhibitors that originate from in vitro screening, demonstrating the validity of pharmacophore mapping in the generation of queries for virtual screening. We discuss the pharmacophore mapping methods that have been successfully employed in the discovery of first-in-class inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651479", "endSection": "abstract" }, { "offsetInBeginSection": 34, "offsetInEndSection": 887, "text": " a popular tool for virtual screening of libraries to identify novel active substances that can be potentially developed into drugs. While they have been applied for years on common drug targets, their application in the discovery of protein-protein interaction inhibitors remains limited. This review describes current pharmacophore modelling methods applied in the discovery of novel inhibitors targeting protein-protein interactions. We first address the mimicry of protein-protein interactions with their respective inhibitors as observed in crystal structure complexes. This mimicry can be exploited to derive a pharmacophore query from protein-protein complex structures. We then discuss several cases where pharmacophore queries were utilized for the discovery of first-in-class inhibitors of their respective protein-protein interaction targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650262", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 1068, "text": "The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features. The best pharmacophore hypotheses were validated by various methods such as test set, decoy set and Cat-Scramble methodology. The validated pharmacophore models were used to screen several small-molecule databases, including Specs, NCI, ChemDiv and Natural product databases to identify the potential dual ACC inhibitors. The virtual hits were then subjected to several filters such as estimated [Formula: see text] value, quantitative estimation of drug-likeness and molecular docking analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334436", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 713, "text": "pharmacophore model has been developed using diverse classes of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors useful in the treatment of human tumours. Among the top 10 generated hypotheses, the second hypothesis, with one hydrogen bond acceptor, one ring aromatic and three hydrophobic features, was found to be the best on the basis of Cat Scramble validation as well as test set prediction (r(training) = 0.89, r(test) = 0.82). The model also maps well to the external test set molecules as well as clinically active molecules and corroborates the docking studies. Finally, 10 hits were identified as potential leads after virtual screening of ZINC database for EGFR TK inhibition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21400356", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 391, "text": "In order to clarify the essential structure-activity relationship for the known Aurora-A inhibitors as well as identify new lead compounds against Aurora-A, 3D pharmacophore models were developed based on the known inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410307", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 854, "text": "computational methods for molecular design are well established in medicinal chemistry research, their application in the field of natural products is still not exhaustively explored. This article gives a short introduction into both the potential for the application of computer-assisted approaches, such as pharmacophore modelling, virtual screening, docking, and neural networking to efficiently access the bioactive metabolites, and the requirements and limitations related to this specific field. The challenge is which selection criteria and/or multiple filtering tools to apply for a target-oriented isolation of potentially bioactive secondary metabolites. Application examples are provided where in silico tools and classical methods used by natural product scientists are used in an effort to maximize their efficacy in drug discovery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16783689", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 331, "text": "pharmacophore models derived from protein binding site atoms without the inclusion of any ligand information have become more popular in virtual screening studies. However, the accuracy of protein-based pharmacophore models for reproducing the critical protein-ligand interactions has never been explicitly assessed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621564", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1259, "text": "Our results demonstrate that there are significant variations in the success of protein-based pharmacophore models to reproduce native contacts and consequently native ligand poses dependent on the details of the pharmacophore generation process. We show that the generation of optimized protein-based pharmacophore models is a promising approach for ligand pose prediction and pose rankings", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621564", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 701, "text": "pharmacophore model does not describe a real molecule or a real association of functional groups but illustrates a molecular recognition of a biological target shared by a group of compounds. Pharmacophores also represent the spatial arrangement of essential interactions in a receptor-binding pocket. Structure based pharmacophores (SBPs) can work both with a free (apo) structure or a macromolecule-ligand complex (holo) structure. The SBP methods that derive pharmacophore from protein-ligand complexes use the potential interactions observed between ligand and protein, whereas, the SBP method that aims to derive pharmacophore from ligand free protein, uses only protein active site information", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651482", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 334, "text": "3D pharmacophore methods are now commonly used as part of more complex workflows in drug discovery campaigns, and have been successfully and extensively applied in virtual screening (VS) approaches. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651486", "endSection": "abstract" } ] }, { "body": "Are there conserved noncoding elements identified between genomes of human and teleosts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19095434", "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "http://www.ncbi.nlm.nih.gov/pubmed/19782672", "http://www.ncbi.nlm.nih.gov/pubmed/19562753", "http://www.ncbi.nlm.nih.gov/pubmed/18047696", "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "http://www.ncbi.nlm.nih.gov/pubmed/17617896", "http://www.ncbi.nlm.nih.gov/pubmed/16556802" ], "ideal_answer": [ "Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages ", "Yes. Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. CNEs have been identified, among others, in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu)." ], "exact_answer": "yes", "type": "yesno", "id": "5544bcde5beec11c10000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1454, "text": "After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1167, "text": "This implicates the \"fish-specific\" whole-genome duplication in the accelerated evolution and the loss of a large number of both copies of duplicated CNEs in teleost fishes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 504, "text": "We found zebrafish conserved noncoding elements (CNEs) with pan-vertebrate as well as fish-specific orthologous sequences from across 200 kb of the zebrafish fgf8a genomic regulatory block to direct reporter expression in patterns consistent with the expression pattern of fgf8a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19782672", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 860, "text": " A significant number of conserved noncoding elements (CNEs) shared between cartilaginous fishes and tetrapods have diverged beyond recognition in teleost fishes. The divergence of CNEs seems to have been initiated in basal ray-finned fishes before the WGD. The fast evolving singleton and duplicated genes as well as the divergent CNEs might have contributed to the diversity of teleost fishes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095434", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 353, "text": "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Ancient vertebrate conserved noncoding elements have been evolving rapidly in teleost fishes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "endSection": "title" }, { "offsetInBeginSection": 463, "offsetInEndSection": 625, "text": "A significant number of conserved noncoding elements (CNEs) shared between cartilaginous fishes and tetrapods have diverged beyond recognition in teleost fishes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095434", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 304, "text": "We have used a transposon-based transgenic assay in zebrafish to evaluate noncoding sequences at the zebrafish ret locus, conserved among teleosts, and at the human RET locus, conserved among mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16556802", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 651, "text": "Using computational analysis and exploiting the diversity of teleost genomes, we identified a cluster of highly conserved noncoding sequences surrounding the Six3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17617896", "endSection": "abstract" } ] }, { "body": "How early during pregnancy does non-invasive cffDNA testing allow sex determination of the fetus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22261468", "http://www.ncbi.nlm.nih.gov/pubmed/25343090", "http://www.ncbi.nlm.nih.gov/pubmed/14680784", "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "http://www.ncbi.nlm.nih.gov/pubmed/24094458", "http://www.ncbi.nlm.nih.gov/pubmed/11746166", "http://www.ncbi.nlm.nih.gov/pubmed/12661284", "http://www.ncbi.nlm.nih.gov/pubmed/23407464", "http://www.ncbi.nlm.nih.gov/pubmed/22192861" ], "ideal_answer": [ "Using cffDNA from maternal blood, the fetal gender can be determined as early as 6 to 10 weeks of gestation (during the first trimester of pregnancy)." ], "exact_answer": [ "6th to 10th week of gestation", "first trimester of pregnancy" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005333", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019849", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012732", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012723", "http://amigo.geneontology.org/amigo/term/GO:0030237", "http://amigo.geneontology.org/amigo/term/GO:0007530", "http://amigo.geneontology.org/amigo/term/GO:0030238" ], "type": "factoid", "id": "57136a7e1174fb1755000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The use of cffDNA in fetal sex determination during the first trimester of pregnancy of female DMD carriers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25343090", "endSection": "title" }, { "offsetInBeginSection": 403, "offsetInEndSection": 561, "text": "We determined fetal sex during the first trimester using a quantitative real-time polymerase chain reaction (PCR) assay of cffDNA in pregnant carriers of DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25343090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Early fetal gender determination using real-time PCR analysis of cell-free fetal DNA during 6th-10th weeks of gestation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "endSection": "title" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1391, "text": "Considerable 97.3% sensitivity and 97.3% specificity were obtained in fetal gender determination which is significant in the first trimester of pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 1001, "text": "Therefore in this study, the probability of detecting sequences on the human Y-chromosome in pregnant women has been evaluated to identify the gender of fetuses. Peripheral blood samples were obtained from 80 pregnant women with gestational age between 6th to 10th weeks and the fetal DNA was extracted from the plasma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 597, "text": "We evaluated the feasibility and accuracy of non-invasive fetal gender determination using quantitative fluorescent-polymerase chain reaction (QF-PCR) analysis of circulating cffDNA in the first-trimester maternal plasma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22192861", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 1103, "text": "This study aims to validate a reliable method for non-invasive prenatal diagnosis of fetal gender using maternal plasma cell-free fetal DNA (cffDNA) for fetal sex assessment in the first trimester of pregnancy and test its clinical utility in the diagnosis of potentially affected pregnancies in carriers of X-linked disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261468", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 991, "text": "We performed a review of the published literature evaluating the use of cffDNA and ultrasound for prenatal determination of fetal sex during the first trimester of pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24094458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The use of cffDNA in fetal sex determination during the first trimester of pregnancy of female DMD carriers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25343090", "endSection": "title" }, { "offsetInBeginSection": 652, "offsetInEndSection": 825, "text": "We performed a review of the published literature evaluating the use of cffDNA and ultrasound for prenatal determination of fetal sex during the first trimester of pregnancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24094458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Fetal Sex Determination using Non-Invasive Method of Cell-free Fetal DNA in Maternal Plasma of Pregnant Women During 6(th)- 10(th) Weeks of Gestation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407464", "endSection": "title" }, { "offsetInBeginSection": 781, "offsetInEndSection": 858, "text": "US allows reliable fetal sex determination only during the second trimester. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14680784", "endSection": "abstract" } ] }, { "body": "Does cortical spreading depression appear in ischemic penumbra following ischemic stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15078545", "http://www.ncbi.nlm.nih.gov/pubmed/20087371", "http://www.ncbi.nlm.nih.gov/pubmed/9740103", "http://www.ncbi.nlm.nih.gov/pubmed/22821441", "http://www.ncbi.nlm.nih.gov/pubmed/10082816", "http://www.ncbi.nlm.nih.gov/pubmed/20700132", "http://www.ncbi.nlm.nih.gov/pubmed/14759495", "http://www.ncbi.nlm.nih.gov/pubmed/8623122", "http://www.ncbi.nlm.nih.gov/pubmed/15879337", "http://www.ncbi.nlm.nih.gov/pubmed/11450018", "http://www.ncbi.nlm.nih.gov/pubmed/18446167", "http://www.ncbi.nlm.nih.gov/pubmed/7944288", "http://www.ncbi.nlm.nih.gov/pubmed/14568331", "http://www.ncbi.nlm.nih.gov/pubmed/22994218", "http://www.ncbi.nlm.nih.gov/pubmed/20660268", "http://www.ncbi.nlm.nih.gov/pubmed/15703392" ], "ideal_answer": [ "Yes, cortical spreading depression appears in ischemic penumbra following ischemic stroke and is associated with expansion of ischemic injury. This has been shown in humans and in animal models." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3455", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013181", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020521" ], "type": "yesno", "id": "514b335dd24251bc05000061", "snippets": [ { "offsetInBeginSection": 393, "offsetInEndSection": 638, "text": "During the subacute phase, the irreversible damage expands into the penumbra: multiple electrical and biological signals are triggered by periinfarct, spreading depression-like depolarizations leading to hypoxia and stepwise increase in lactate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994218", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Experimental and clinical studies indicate that waves of cortical spreading depolarization (CSD) appearing in the ischemic penumbra contribute to secondary lesion growth.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20700132", "endSection": "sections.0" }, { "offsetInBeginSection": 665, "offsetInEndSection": 854, "text": "Analysis of MCA occlusions (MCAOs) revealed a first CSD wave starting off during ischemic decline at the emerging core region, propagating concentrically over large portions of left cortex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20700132", "endSection": "sections.0" }, { "offsetInBeginSection": 855, "offsetInEndSection": 974, "text": "Subsequent recurrent waves of CSD did not propagate concentrically but preferentially circled around the ischemic core.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20700132", "endSection": "sections.0" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1195, "text": "In the vicinity of the core region, CSDs were coupled to waves of predominantly vasoconstrictive CBF(LSF) responses, resulting in further decline of CBF in the entire inner penumbra and in expansion of the ischemic core.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20700132", "endSection": "sections.0" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1347, "text": "We conclude that CSDs and corresponding CBF responses follow a defined spatiotemporal order, and contribute to early evolution of ischemic territories.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20700132", "endSection": "sections.0" }, { "offsetInBeginSection": 562, "offsetInEndSection": 801, "text": "Astrocytes in the metabolically compromised ischemic penumbra-like area showed a long lasting swelling response to spontaneous spreading depolarizations despite rapid dendritic recovery in a photothrombotic occlusion model of focal stroke.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821441", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Spontaneous spreading depolarizations (SDs) occur in the penumbra surrounding ischemic core.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20660268", "endSection": "sections.0" }, { "offsetInBeginSection": 93, "offsetInEndSection": 411, "text": "These SDs, often referred to as peri-infarct depolarizations, cause vasoconstriction and recruitment of the penumbra into the ischemic core in the critical first hours after focal ischemic stroke; however, the real-time spatiotemporal dynamics of SD-induced injury to synaptic circuitry in the penumbra remain unknown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20660268", "endSection": "sections.0" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1685, "text": "We propose that metabolic stress resulting from recurring SDs facilitates acute injury at the level of dendrites and dendritic spines in metabolically compromised tissue, expediting penumbral recruitment into the ischemic core.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20660268", "endSection": "sections.0" }, { "offsetInBeginSection": 316, "offsetInEndSection": 432, "text": "Although the mechanism remains unknown, SDs show delayed electrophysiological recovery within the ischemic penumbra.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20087371", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Spreading depression-like peri-infarct depolarizations not only characterize but also worsen penumbra conditions in cortical border zones of experimental focal ischemia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703392", "endSection": "sections.0" }, { "offsetInBeginSection": 1372, "offsetInEndSection": 1587, "text": "We conclude that in focal ischemia, transient peri-infarct depolarizations emerge not only in cortical but also in striatal gray matter, thereby demonstrating the existence of subcortical zones of ischemic penumbra.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703392", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Spreading depression (SD) has been demonstrated following focal ischemia, and the additional workload imposed by SD on a tissue already compromised by a marked reduction in blood flow may contribute to the evolution of irreversible damage in the ischemic penumbra.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14759495", "endSection": "sections.0" }, { "offsetInBeginSection": 1566, "offsetInEndSection": 1811, "text": "While the changes in the glucose-related metabolites persisted during recovery even in anterior portions of the cortex in both groups in the aftermath of the SD, the magnitude of the changes was greater in the penumbra than in the normal cortex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14759495", "endSection": "sections.0" }, { "offsetInBeginSection": 1812, "offsetInEndSection": 1979, "text": "SD appears to impose an equivalent increase in energy demands in control and ischemic brain, but the ability of the penumbra to recover from the insult is compromised.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14759495", "endSection": "sections.0" }, { "offsetInBeginSection": 1980, "offsetInEndSection": 2215, "text": "Thus, increasing the energy imbalance in the penumbra after multiple SDs may hasten the deterioration of the energy status of the tissue and eventually contribute to terminal depolarization and cell death, particularly in the penumbra.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14759495", "endSection": "sections.0" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1640, "text": "It is suggested that the limited survival of the penumbra is due to periinfarct depolarizations, which result in repeated episodes of tissue hypoxia, because the increased metabolic workload is not coupled to an adequate increase of collateral blood supply.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7944288", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 243, "text": "Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8623122", "endSection": "sections.0" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1580, "text": "Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8623122", "endSection": "sections.0" }, { "offsetInBeginSection": 152, "offsetInEndSection": 376, "text": "One current but controversial hypothesis is that this penumbra tissue often eventually dies because of the metabolic stress imposed by multiple cortical spreading depression (CSD) waves, that is, by ischemic depolarizations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9740103", "endSection": "sections.0" }, { "offsetInBeginSection": 479, "offsetInEndSection": 739, "text": "After simulated infarction, the model displays the linear relation between final infarct size and the number of CSD waves traversing the penumbra that has been reported experimentally, although damage with each individual wave progresses nonlinearly with time.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9740103", "endSection": "sections.0" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1413, "text": "These findings support the hypothesis that CSD waves play an important causal role in the death of ischemic penumbra tissue.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9740103", "endSection": "sections.0" }, { "offsetInBeginSection": 364, "offsetInEndSection": 484, "text": "MCAO also triggers periodic periinfarction depolarizing waves (PIDs) in the ischemic penumbra, the territory of salvage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10082816", "endSection": "sections.0" }, { "offsetInBeginSection": 151, "offsetInEndSection": 255, "text": "Here, the effects of SD at reduced flow conditions as encountered in the ischemic penumbra are examined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11450018", "endSection": "sections.0" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1397, "text": "The experiments illustrate how peri-infarct depolarizations may detrimentally affect the penumbra.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11450018", "endSection": "sections.0" }, { "offsetInBeginSection": 667, "offsetInEndSection": 865, "text": "In the second series of experiments, periinfarct depolarizations (PIDs) were recorded with an extracellular DC electrode at two locations in the ischemic penumbra for the initial 3 h following MCAO.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14568331", "endSection": "sections.0" }, { "offsetInBeginSection": 656, "offsetInEndSection": 850, "text": "In vivo two-photon microscopy of green fluorescent protein-expressing neurons in this penumbra-like area at risk revealed that SDs were temporally correlated with rapid (<6 s) dendritic beading.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20660268", "endSection": "sections.0" } ] }, { "body": "Is phospholamban a regulatory/inhibitory protein of the Ca ATPase SERCA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16564056", "http://www.ncbi.nlm.nih.gov/pubmed/19395670", "http://www.ncbi.nlm.nih.gov/pubmed/23308118", "http://www.ncbi.nlm.nih.gov/pubmed/15134458", "http://www.ncbi.nlm.nih.gov/pubmed/19112098", "http://www.ncbi.nlm.nih.gov/pubmed/22971924", "http://www.ncbi.nlm.nih.gov/pubmed/24101520", "http://www.ncbi.nlm.nih.gov/pubmed/9845327", "http://www.ncbi.nlm.nih.gov/pubmed/18045856", "http://www.ncbi.nlm.nih.gov/pubmed/19840770", "http://www.ncbi.nlm.nih.gov/pubmed/21576492", "http://www.ncbi.nlm.nih.gov/pubmed/10024311", "http://www.ncbi.nlm.nih.gov/pubmed/11559781", "http://www.ncbi.nlm.nih.gov/pubmed/10951187", "http://www.ncbi.nlm.nih.gov/pubmed/17286271", "http://www.ncbi.nlm.nih.gov/pubmed/19708671", "http://www.ncbi.nlm.nih.gov/pubmed/19158349" ], "ideal_answer": [ "Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca2+]i and contractility in these muscles.The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. \u03b2-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.", "Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+) up-take by this organelle and is inhibited in a reversible manner by phospholamban. When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance.Thus, alleviation of phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option for heart failure and cardiomyopathy." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053498" ], "type": "yesno", "id": "5501b3b3e9bde69634000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. \u03b2-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle. In membranes, PLN forms pentamers that have been proposed to function either as a storage for active monomers or as ion channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19708671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 493, "text": "Calcium transport across the membrane of the sarcoplasmic reticulum (SR) plays an important role in the regulation of heart muscle contraction and relaxation. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+) up-take by this organelle and is inhibited in a reversible manner by phospholamban, another SR membrane protein. Thus, alleviation of phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option for heart failure and cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19158349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19112098", "endSection": "abstract" }, { "offsetInBeginSection": 1312, "offsetInEndSection": 1508, "text": "In larger mammals, a higher fraction of SERCA2a pumps are regulated by phospholamban, and this may influence therapeutic strategies to enhance cardiac contractility and functional cardiac reserve.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19112098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and this inhibition is relieved by Ca(2+) calmodulin-dependent protein kinase II (CaM kinase II) phosphorylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045856", "endSection": "abstract" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1622, "text": "These findings suggest that PLB is an important modulator of gastric antrum smooth muscle contractility by modulation of SR Ca(2+) release and CaM kinase II activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045856", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1183, "text": "The function of the SERCA pump is modulated by the endogenous molecules phospholamban (PLB) and sarcolipin (SLN), expressed in cardiac and skeletal muscles. The mechanism of action of PLB on SERCA is well characterized, whereas that of SLN is only beginning to be understood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17286271", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 94, "text": " Phospholamban (PLB) is an inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11559781", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1353, "text": "These results show that alteration of the PLB:SERCA ratio can significantly modulate smooth muscle [Ca2+]i.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11559781", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1237, "text": "Phospholamban expressed in cardiac muscle and sarcolipin expressed in skeletal muscle regulate SERCA activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10951187", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 446, "text": "Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca2+]i and contractility in these muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10024311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA 2a) depends on the phosphorylation state of phospholamban (PLB). When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9845327", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 375, "text": " Ca(2+) reuptake occurs via sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19395670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23308118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Phospholamban (PLN) is the endogenous inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), the integral membrane enzyme responsible for 70\ufffd% of the removal of Ca(2+) from the cytosol, inducing cardiac muscle relaxation in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22971924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Phospholamban (PLB) is an integral membrane protein regulating Ca(2+) transport through inhibitory interaction with sarco(endo)plasmic reticulum calcium ATPase (SERCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19840770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16564056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16564056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "We used EPR spectroscopy to probe directly the interaction between phospholamban (PLB) and its regulatory target, the sarcoplasmic reticulum Ca-ATPase (SERCA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15134458", "endSection": "abstract" } ] }, { "body": "What is TFBSshape?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24214955" ], "ideal_answer": [ "To utilize DNA shape information when analysing the DNA binding specificities of TFs, the TFBSshape database was developed for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0051090", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001665" ], "type": "summary", "id": "56a3a6c9496b62f23f000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "TFBSshape: a motif database for DNA shape features of transcription factor binding sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "title" }, { "offsetInBeginSection": 588, "offsetInEndSection": 1465, "text": "To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1148, "text": "To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1410, "text": "The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1780, "text": "As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 871, "text": "DNA structural features refine the description of TF binding specificities and provide mechanistic insights into protein-DNA recognition. Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 1144, "text": "To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 871, "text": "Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1466, "text": "The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1469, "text": "As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214955", "endSection": "abstract" } ] }, { "body": "Is Alpers disease inherited in an autosomal recessive mode?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22000311", "http://www.ncbi.nlm.nih.gov/pubmed/15122711", "http://www.ncbi.nlm.nih.gov/pubmed/22006280", "http://www.ncbi.nlm.nih.gov/pubmed/1861211", "http://www.ncbi.nlm.nih.gov/pubmed/21451360", "http://www.ncbi.nlm.nih.gov/pubmed/16181814", "http://www.ncbi.nlm.nih.gov/pubmed/7897414" ], "ideal_answer": [ "Alpers disease is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease.", "Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder" ], "exact_answer": "yes", "type": "yesno", "id": "5718a69e7de986d80d00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22006280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16181814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15122711", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 883, "text": "Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7897414", "endSection": "abstract" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1317, "text": "Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7897414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Alpers syndrome is a rare autosomal recessive hepatocerebral degenerative disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22000311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Alpers disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21451360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16181814", "endSection": "abstract" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1829, "text": "We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1861211", "endSection": "abstract" } ] }, { "body": "Is vemurafenib effective for hairy-cell leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25480661", "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "http://www.ncbi.nlm.nih.gov/pubmed/25148599", "http://www.ncbi.nlm.nih.gov/pubmed/26352686", "http://www.ncbi.nlm.nih.gov/pubmed/24137951", "http://www.ncbi.nlm.nih.gov/pubmed/25774734" ], "ideal_answer": [ "Yes, vemurafenib is highly effective in patients with relapsed or refractory hairy-cell leukemia." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007943", "http://www.disease-ontology.org/api/metadata/DOID:285" ], "type": "yesno", "id": "56c02bc3ef6e394741000018", "snippets": [ { "offsetInBeginSection": 1961, "offsetInEndSection": 2090, "text": "CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26352686", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1600, "text": "Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25480661", "endSection": "abstract" }, { "offsetInBeginSection": 2204, "offsetInEndSection": 2344, "text": "The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25774734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "endSection": "title" }, { "offsetInBeginSection": 113, "offsetInEndSection": 453, "text": "Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 881, "text": "We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 \u00d7 240 mg) daily without inducing major toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 591, "text": "The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25148599", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "[Successful use of vemurafenib in a patient with resistant hairy cell leukemia].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137951", "endSection": "title" }, { "offsetInBeginSection": 1781, "offsetInEndSection": 2091, "text": "The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26352686", "endSection": "abstract" }, { "offsetInBeginSection": 1934, "offsetInEndSection": 2050, "text": "A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26352686", "endSection": "abstract" }, { "offsetInBeginSection": 1937, "offsetInEndSection": 2054, "text": "A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26352686", "endSection": "abstract" }, { "offsetInBeginSection": 2148, "offsetInEndSection": 2287, "text": "The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25774734", "endSection": "abstract" } ] }, { "body": "Which are the inhibitors of histone methyltransferases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23557020", "http://www.ncbi.nlm.nih.gov/pubmed/22522911", "http://www.ncbi.nlm.nih.gov/pubmed/22924785", "http://www.ncbi.nlm.nih.gov/pubmed/21940714", "http://www.ncbi.nlm.nih.gov/pubmed/23077658", "http://www.ncbi.nlm.nih.gov/pubmed/23092945", "http://www.ncbi.nlm.nih.gov/pubmed/23139138", "http://www.ncbi.nlm.nih.gov/pubmed/20567762", "http://www.ncbi.nlm.nih.gov/pubmed/23379261", "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "http://www.ncbi.nlm.nih.gov/pubmed/22781932", "http://www.ncbi.nlm.nih.gov/pubmed/23011794", "http://www.ncbi.nlm.nih.gov/pubmed/22964322", "http://www.ncbi.nlm.nih.gov/pubmed/22420752", "http://www.ncbi.nlm.nih.gov/pubmed/19860425", "http://www.ncbi.nlm.nih.gov/pubmed/22560341", "http://www.ncbi.nlm.nih.gov/pubmed/22429326", "http://www.ncbi.nlm.nih.gov/pubmed/22904200", "http://www.ncbi.nlm.nih.gov/pubmed/20556507", "http://www.ncbi.nlm.nih.gov/pubmed/21546573", "http://www.ncbi.nlm.nih.gov/pubmed/21936531", "http://www.ncbi.nlm.nih.gov/pubmed/22665483" ], "ideal_answer": [ "In general, histone methyltransferases (HMTs) have no widely approved high-throughput screening assay format, and therefore reference inhibitors are not available for many of the HMTs. However, there are several selective HMT inhibitors: Trichostatin A (TSA), BIX-01294 and its derivative TM2-115, 2,4-pyridinedicarboxylic acid (2,4-PDCA), 3-deazaneplanocin A (DZNep), Psammaplin A (PsA) and Sulforaphane (SFN)." ], "exact_answer": [ [ "BIX-01294" ], [ "TM2-115" ], [ "2,4-pyridinedicarboxylic acid", "2,4-PDCA" ], [ "3-deazaneplanocin A", "DZNep" ], [ "Trichostatin A", "TSA" ], [ "Psammaplin A", "PsA" ], [ "Sulforaphane", "SFN" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056572", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042054" ], "type": "list", "id": "5166f41a298dcd4e5100005b", "snippets": [ { "offsetInBeginSection": 559, "offsetInEndSection": 722, "text": "However, in general, HMTs have no widely accepted high-throughput screening (HTS) assay format, and reference inhibitors are not available for many of the enzymes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23557020", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Small-molecule histone methyltransferase inhibitors display rapid antimalarial activity against all blood stage forms in Plasmodium falciparum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23011794", "endSection": "title" }, { "offsetInBeginSection": 299, "offsetInEndSection": 675, "text": "We synthesized a compound library based upon a known specific inhibitor (BIX-01294) of the human G9a histone methyltransferase. Two compounds, BIX-01294 and its derivative TM2-115, inhibited P. falciparum 3D7 parasites in culture with IC(50) values of ~100 nM, values at least 22-fold more potent than their apparent IC(50) toward two human cell lines and one mouse cell line.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23011794", "endSection": "sections.0" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1486, "text": "Together, these results suggest that BIX-01294 and TM2-115 inhibit malaria parasite histone methyltransferases, resulting in rapid and irreversible parasite death.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23011794", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22924785", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 329, "text": "A total of 55 adenosine-containing compounds were designed and synthesized, among which several potent DOT1L inhibitors were identified with K(i) values as low as 0.5 nM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22924785", "endSection": "sections.0" }, { "offsetInBeginSection": 606, "offsetInEndSection": 773, "text": "Several new reagents and assays were developed to aid in the identification of EZH2 inhibitors, and these were used to execute two high-throughput screening campaigns.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22904200", "endSection": "sections.0" }, { "offsetInBeginSection": 83, "offsetInEndSection": 396, "text": "Of the five histone methyltransferases known to mediate methylation of the lysine 9 residue of histone H3 (H3K9), euchromatic histone-lysine N-methyltransferase 2 (EHMT2; also known as G9a) has been shown to be a primary mediator of H3K9 dimethylation; BIX-01294 has been shown to be a specific inhibitor of EHMT2", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22781932", "endSection": "sections.0" }, { "offsetInBeginSection": 533, "offsetInEndSection": 675, "text": "We hypothesised that inhibition of EHMT2 by BIX-01294 would result in reduced levels of H3K9 dimethylation and compromised embryo development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22781932", "endSection": "sections.0" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1135, "text": "We also demonstrate that peptides that mimic SET1 family Win motif sequences inhibit H3K4 dimethylation by the MLL1 core complex with varying degrees of efficiency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665483", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22420752", "endSection": "title" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1451, "text": "Inhibition studies of ccKDM5B showed both in vitro and in cell inhibition of ccKDM5B by 2,4-pyridinedicarboxylic acid (2,4-PDCA) with a potency similar to that reported for the HDM KDM4C.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22420752", "endSection": "sections.0" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1220, "text": "Treatment with 3-deazaneplanocin A (DZNep), an inhibitor of H3K27me3 and H4K20me3, significantly enhanced the BZLF1 transcription in Raji cells when in combination with an HDAC inhibitor, trichostatin A (TSA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "endSection": "sections.0" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1552, "text": "All assays allowed profiling of known SET7/9 and LSD1 inhibitors. The results demonstrate that the optimized LANCE Ultra and AlphaLISA assay formats provide a relevant biochemical screening approach toward the identification of small-molecule inhibitors of HMTs and HDMs that could lead to novel epigenetic therapies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21940714", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21936531", "endSection": "title" }, { "offsetInBeginSection": 145, "offsetInEndSection": 273, "text": "We used structure- and mechanism-based design to discover several potent inhibitors of DOT1L with IC(50) values as low as 38 nM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21936531", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Inhibition of histone lysine methylation enhances cancer-testis antigen expression in lung cancer cells: implications for adoptive immunotherapy of cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21546573", "endSection": "title" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1205, "text": "Short hairpin RNAs were used to inhibit several histone methyltransferases (KMT) and histone demethylases (KDM) that mediate histone methylation and repress gene expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21546573", "endSection": "sections.0" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1449, "text": "DZNep, a pharmacologic inhibitor of KMT6 expression, recapitulated the effects of KMT6 knockdown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21546573", "endSection": "sections.0" }, { "offsetInBeginSection": 296, "offsetInEndSection": 693, "text": "Recent evidence shows that S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors (AHI) such as 3-deazaneplanocin A (DZNep) modulate chromatin through indirect inhibition of histone methyltransferases including EZH2. We investigated the biological effects of AdoHcy hydrolase inhibition using DZNep and its structural analogues 3-deazaadenosine (DZA) and neplanocin A (Nep A) in breast cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20556507", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "A chemiluminescence-based method for identification of histone lysine methyltransferase inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20567762", "endSection": "title" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1226, "text": "The method is particularly well suited for detection of inhibitors acting by the desired histone peptide competitive mechanism and is applicable to testing other HMTs, demonstrated here with the G9a homolog EHMT1, also known as GLP.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20567762", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "This study reports the pharmacokinetics and tissue distribution of a novel histone deacetylase and DNA methyltransferase inhibitor, psammaplin A (PsA), in mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23139138", "endSection": "sections.0" }, { "offsetInBeginSection": 328, "offsetInEndSection": 513, "text": "Human diet contains many histone deacetylase (HDAC) inhibitors, such as the bioactive component sulforaphane (SFN), whose epigenetic effects on MSTN gene in satellite cells are unknown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23092945", "endSection": "sections.0" }, { "offsetInBeginSection": 515, "offsetInEndSection": 672, "text": "We found that DNA methyltransferase inhibitor (5-Aza-2'-deoxycytidine) and histone deacetylase inhibitor (trichostatin A) reduced leptin receptor expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22560341", "endSection": "sections.0" }, { "offsetInBeginSection": 735, "offsetInEndSection": 885, "text": "However, histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate (NaBt) significantly increased Wnt5a mRNA expression in SW620.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522911", "endSection": "sections.0" } ] }, { "body": "What is the main characteristic of Amyotrophic Lateral Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8959997", "http://www.ncbi.nlm.nih.gov/pubmed/16228969", "http://www.ncbi.nlm.nih.gov/pubmed/17128093", "http://www.ncbi.nlm.nih.gov/pubmed/25384799" ], "ideal_answer": [ "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons. ", "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons." ], "type": "summary", "id": "56b469448525abca1e000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Motor neuron diseases (MND), such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are progressive neurodegenerative diseases that share the common characteristic of upper and/or lower motor neuron degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16228969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17128093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "There are four main hypotheses about the cause of ALS: excitotoxicity linked to glutamate receptor overactivation; mutation of the superoxide dismutase gene; production of autoantibodies to calcium channels; neurofilament accumulation. The motoneuron degeneration characteristic of ALS could be caused by any one or a combination of these mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8959997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1 mutations suggest that neurodegeneration is a non-cell autonomous process where microglial cells influence disease progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25384799", "endSection": "abstract" } ] }, { "body": "Which genes are regulated by MEF-2 in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17518763", "http://www.ncbi.nlm.nih.gov/pubmed/8035789", "http://www.ncbi.nlm.nih.gov/pubmed/17938175", "http://www.ncbi.nlm.nih.gov/pubmed/8321243", "http://www.ncbi.nlm.nih.gov/pubmed/21244855", "http://www.ncbi.nlm.nih.gov/pubmed/16049055", "http://www.ncbi.nlm.nih.gov/pubmed/8366095", "http://www.ncbi.nlm.nih.gov/pubmed/21812548", "http://www.ncbi.nlm.nih.gov/pubmed/10998641", "http://www.ncbi.nlm.nih.gov/pubmed/9043061", "http://www.ncbi.nlm.nih.gov/pubmed/1328854", "http://www.ncbi.nlm.nih.gov/pubmed/7982978", "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "http://www.ncbi.nlm.nih.gov/pubmed/1532229", "http://www.ncbi.nlm.nih.gov/pubmed/19893013", "http://www.ncbi.nlm.nih.gov/pubmed/10794526", "http://www.ncbi.nlm.nih.gov/pubmed/15491989", "http://www.ncbi.nlm.nih.gov/pubmed/15040454", "http://www.ncbi.nlm.nih.gov/pubmed/8449897", "http://www.ncbi.nlm.nih.gov/pubmed/11770083", "http://www.ncbi.nlm.nih.gov/pubmed/8674419", "http://www.ncbi.nlm.nih.gov/pubmed/20075332", "http://www.ncbi.nlm.nih.gov/pubmed/12805933" ], "ideal_answer": [ "COX-2, ANF, estrogen receptor (ER)alpha gene, calsequestrin gene, casq2, cTnT, MCK, alpha-cardiac actin, sarco(endo)plasmic reticulum Ca2+-ATPase, SERCA, MLC-2, alpha-cardiac myosin heavy chain gene, phosphoglycerate mutase and PGAM-M are regulated by MEF-2 in the heart" ], "exact_answer": [ [ "COX-2" ], [ "ANF" ], [ "estrogen receptor (ER)alpha gene" ], [ "calsequestrin gene", "casq2" ], [ "cTnT" ], [ "MCK" ], [ "alpha-cardiac actin" ], [ "sarco(endo)plasmic reticulum Ca2+-ATPase", "SERCA" ], [ "MLC-2" ], [ "alpha-cardiac myosin heavy chain gene" ], [ "phosphoglycerate mutase", "PGAM-M" ], [ "cardiac troponin C", "cTnC" ] ], "concepts": [ "http://www.uniprot.org/uniprot/MYEF2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.uniprot.org/uniprot/MYEF2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "list", "id": "517539af8ed59a060a000026", "snippets": [ { "offsetInBeginSection": 1560, "offsetInEndSection": 1654, "text": "Inhibition of MEF2A using siRNA attenuated HB-EGF-induced COX-2, ANF expression and cell size.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21244855", "endSection": "sections.0" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1077, "text": "This genetic reprogramming coincides with a pronounced increase in expression of the estrogen receptor (ER)alpha gene, which we show to be a direct MEF2 target gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19893013", "endSection": "sections.0" }, { "offsetInBeginSection": 120, "offsetInEndSection": 154, "text": "cardiac calsequestrin gene (casq2)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17938175", "endSection": "sections.0" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1732, "text": "Functional studies demonstrated that site-directed mutagenesis of the proximal MEF-2 and CArG box sites significantly decreased the transcription of the gene in cardiac and skeletal muscle cells, indicating that they are important to drive cardiac and skeletal muscle-specific transcription of the casq2 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17938175", "endSection": "sections.0" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1025, "text": "DTEF-1 also interacts with MEF- 2 by coimmunoprecipitation and independently or cooperatively (with MEF-2) trans-activates the cTnT promoter", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16049055", "endSection": "sections.0" }, { "offsetInBeginSection": 432, "offsetInEndSection": 822, "text": "An 85-bp region within the enhancer is highly conserved between human and mouse and contains a central AT-rich site, which is essential for enhancer activity. This site binds myocyte enhancer factor (MEF)2 factors, principally MEF2D and MEF2A in cardiocyte nuclear extracts. These results are discussed in the context of MEF2 activity and of the regulation of the alpha-cardiac actin locus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15491989", "endSection": "sections.0" }, { "offsetInBeginSection": 261, "offsetInEndSection": 424, "text": "The cis-acting elements, MEF-2, E boxes and A/T rich elements present in the enhancer region of the mouse MCK gene are known to regulate the expression of the gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15040454", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5 -regulatory region.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805933", "endSection": "sections.0" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1252, "text": "Among the DNA cis-elements present in these two regulatory regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF-1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb, there is no significant homology among the SERCA2 genes cloned.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805933", "endSection": "sections.0" }, { "offsetInBeginSection": 554, "offsetInEndSection": 890, "text": "The cardiac calsequestrin gene consists of 11 exons and its 5' flanking region is characterized by the presence of a TATA-like box, muscle specific promoter elements such as 7 E-boxes, 1 MEF-2, 1 MCBF and 1 Repeat (musS) motifs, as well as several muscle non-specific transcriptional elements (AP-2A, NRE1, NRE2, p53, Spel and TFI-IIA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11770083", "endSection": "sections.0" }, { "offsetInBeginSection": 336, "offsetInEndSection": 516, "text": "our laboratory identified a 28 bp HF-la/MEF-2 element in the MLC-2v promoter region, which confers cardiac ventricular chamber-specific gene expression during murine cardiogenesis,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9043061", "endSection": "sections.0" }, { "offsetInBeginSection": 501, "offsetInEndSection": 742, "text": "In this study, we investigated T3R alpha 1-vs. T3R beta 1-specific interactions with the myocyte enhancer-specific factor-2 (MEF-2) on the expression of the SERCA 2 gene in transient transfection assays in embryonal heart-derived H9c2 cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "endSection": "sections.0" }, { "offsetInBeginSection": 1759, "offsetInEndSection": 1902, "text": "point to T3R isoform-specific interactions with a cell type-specific transcription factor (MEF-2) in the regulation of SERCA 2 gene expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "endSection": "sections.0" }, { "offsetInBeginSection": 519, "offsetInEndSection": 874, "text": "In multiple independent transgenic mouse lines, we found that both a 250 base pair myosin light chain-2 ventricular promoter fragment, as well as a dimerized 28 bp sub-element (HF-1) containing binding sites for HF1a and HF1b/MEF2 factors, directed ventricular-specific reporter expression from as early as the endogenous gene, at day 7.5-8.0 post coitum.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8674419", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Myocyte-specific enhancer-binding factor (MEF-2) regulates alpha-cardiac myosin heavy chain gene expression in vitro and in vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8366095", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 288, "text": "In the MLC-2 gene, an AT-rich element (HF-1b) which contains a consensus MEF-2 site is required for cardiac tissue-specific expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8321243", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the alpha-cardiac myosin heavy chain gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8449897", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "In order to analyze the transcriptional regulation of the muscle-specific subunit of the human phosphoglycerate mutase (PGAM-M) gene, chimeric genes composed of the upstream region of the PGAM-M gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1328854", "endSection": "sections.0" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1650, "text": "These observations define the PGAM-M enhancer as the only cardiac- and skeletal-muscle-specific enhancer characterized thus far that is mainly activated through MEF-2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1328854", "endSection": "sections.0" }, { "offsetInBeginSection": 223, "offsetInEndSection": 457, "text": "Transcription of each gene is independently controlled but coordinately regulated. During each embryogenesis, the beta-MHC gene is expressed as part of the cardiac myogenic program under the control of NKX-2.5, MEF-2C, and GATA-4/5/6.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10998641", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 713, "text": "We have characterized the specific DNA regulatory elements responsible for the function of the human cardiac troponin C gene (cTnC) muscle-specific enhancer in myogenic cells. We used functional transient transfection assays with deletional and site-specific mutagenesis to evaluate the role of the conserved sequence elements. Gel electrophoresis mobility shift assays (EMSA) demonstrated the ability of the functional sites to interact with nuclear proteins. We demonstrate that three distinct transcription activator binding sites commonly found in muscle-specific enhancers (a MEF-2 site, a MEF-3 site, and at least four redundant E-box sites) all contribute to full enhancer activity but a CArG box does not.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10794526", "endSection": "sections.0" } ] }, { "body": "Is there an association between TERT promoter mutation and survival of glioma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25081751", "http://www.ncbi.nlm.nih.gov/pubmed/25314060", "http://www.ncbi.nlm.nih.gov/pubmed/24722048", "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "http://www.ncbi.nlm.nih.gov/pubmed/26061753" ], "ideal_answer": [ "Yes, TERT mutation is associated with survival of glioma patients and was suggested as a bio-marker of gliomas." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005910" ], "type": "yesno", "id": "56c095b7ef6e394741000025", "snippets": [ { "offsetInBeginSection": 148, "offsetInEndSection": 254, "text": "Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25081751", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 2166, "text": "Kaplan-Meier's survival analysis showed that TERT promoter mutation (P=0.037), Isocitrate dehydrogenase (IDH) mutation (P<0.001), and 1p/19q codeletion (P<0.001) were associated with favorable overall survival (OS). In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). Consistent with this observation, in the subset of 97 IDH-mutated astrocytomas, 14 TERT promoter-mutated tumors showed longer PFS (P=0.001) and OS (P=0.001). In contrast, among the subset of 74 IDH wild-type lower-grade gliomas with intact 1p/19q, TERT promoter mutation was associated with shorter PFS (P=0.001) and OS (P=0.001). Similarly, in the subset of 65 IDH wild-type astrocytomas, 16 TERT promoter-mutated tumors exhibited unfavorable PFS (P=0.007) and OS (P=0.008). Our results indicate that when combined with IDH status, TERT promoter mutation contributes to prognostic subgroups of lower-grade astrocytic tumors or 1p/19q intact lower-grade gliomas and this may further refine future molecular classification of lower-grade gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25081751", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 857, "text": "RESULTS: TERTp-mut identified in 60.8% of gliomas (491 out of 807) was globally associated with poorer outcome (Hazard ratio (HR)=1.50). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25314060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "TERT promoter mutations lead to high transcriptional activity under hypoxia and temozolomide treatment and predict poor prognosis in gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "endSection": "title" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1323, "text": "Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1608, "text": "TERT promoter mutations maintained its ability of inducing high transcriptional activity even under hypoxic and TMZ treatment conditions, and the presence of mutations was associated with poor prognosis in glioma patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1579, "text": "Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24722048", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1385, "text": "Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.CONCLUSION: TERT promoter mutations were specific to gliomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1251, "text": "We defined, based on TERTp-mut and IDH mutation status, four prognostic groups: (1) TERTp-mut and IDH-mut associated with 1p19q codeletion, overall survival (OS)>17 years; (2) TERTp-wt and IDH-mut, associated with TP53 mutation, OS=97.5 months; (3) TERTp-wt and IDH-wt, with no specific association, OS=31.6 months; (4) TERTp-mut and IDH-wt, associated with EGFR amplification, OS=15.4 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25314060", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 255, "text": "Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25081751", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1421, "text": "In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25081751", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1581, "text": "The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26061753", "endSection": "abstract" }, { "offsetInBeginSection": 930, "offsetInEndSection": 1299, "text": "Mutations were detected in gliomas, but not in meningiomas, pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or peripheral blood of glioma patients. Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "endSection": "abstract" } ] }, { "body": "Which JAK (Janus kinase) inhibitor is approved for treatment of rheumatoid arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19587388", "http://www.ncbi.nlm.nih.gov/pubmed/20732649", "http://www.ncbi.nlm.nih.gov/pubmed/22374445", "http://www.ncbi.nlm.nih.gov/pubmed/22899318", "http://www.ncbi.nlm.nih.gov/pubmed/22121136", "http://www.ncbi.nlm.nih.gov/pubmed/22777068", "http://www.ncbi.nlm.nih.gov/pubmed/23599436", "http://www.ncbi.nlm.nih.gov/pubmed/23212593", "http://www.ncbi.nlm.nih.gov/pubmed/23961674", "http://www.ncbi.nlm.nih.gov/pubmed/24285764", "http://www.ncbi.nlm.nih.gov/pubmed/19404006", "http://www.ncbi.nlm.nih.gov/pubmed/19565475", "http://www.ncbi.nlm.nih.gov/pubmed/20701804", "http://www.ncbi.nlm.nih.gov/pubmed/22006202", "http://www.ncbi.nlm.nih.gov/pubmed/24193189", "http://www.ncbi.nlm.nih.gov/pubmed/22209716", "http://www.ncbi.nlm.nih.gov/pubmed/22147632", "http://www.ncbi.nlm.nih.gov/pubmed/23523202", "http://www.ncbi.nlm.nih.gov/pubmed/22252297", "http://www.ncbi.nlm.nih.gov/pubmed/20233177", "http://www.ncbi.nlm.nih.gov/pubmed/23384668", "http://www.ncbi.nlm.nih.gov/pubmed/22971156", "http://www.ncbi.nlm.nih.gov/pubmed/24218541", "http://www.ncbi.nlm.nih.gov/pubmed/23642011", "http://www.ncbi.nlm.nih.gov/pubmed/21884580", "http://www.ncbi.nlm.nih.gov/pubmed/21105711", "http://www.ncbi.nlm.nih.gov/pubmed/22460142", "http://www.ncbi.nlm.nih.gov/pubmed/23627915", "http://www.ncbi.nlm.nih.gov/pubmed/24013646", "http://www.ncbi.nlm.nih.gov/pubmed/21548952", "http://www.ncbi.nlm.nih.gov/pubmed/21952978" ], "ideal_answer": [ "Tofacitinib (or CP690.550) is an oral JAK (Janus kinase) inhibitor that is approved for treatment of rheumatoid arthritis. Tofacitinib inhibits JAK family kinase members, in particular JAK1 and JAK3, achieving a broad limitation of inflammation by interfering with several cytokine receptors. Tofacitinib has also a proven efficacy as an immunosuppressive regimen after renal transplantation. \nGLPG-0634 and INCB18424 are other JAK kinase inhibitors that are being studied for treatment of rheumatoid arthritis." ], "exact_answer": [ "tofacitinib" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.uniprot.org/uniprot/JAK2_PIG", "http://www.uniprot.org/uniprot/JAK2_MOUSE", "http://www.uniprot.org/uniprot/JAK2_RAT", "http://www.uniprot.org/uniprot/JAK2_HUMAN", "http://www.uniprot.org/uniprot/JAK3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004713", "http://www.uniprot.org/uniprot/JAK3_MOUSE", "http://www.uniprot.org/uniprot/JAK1_MOUSE", "http://www.uniprot.org/uniprot/JAK3_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053614", "http://www.uniprot.org/uniprot/JAK2_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053613", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053612", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033673", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.uniprot.org/uniprot/JAK1_DANRE", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://www.uniprot.org/uniprot/JAK1_CYPCA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053616", "http://www.uniprot.org/uniprot/JAK2_CHICK", "http://www.uniprot.org/uniprot/JAK1_HUMAN" ], "type": "factoid", "id": "53357193d6d3ac6a34000047", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Tofacitinib: The First Janus Kinase (JAK) inhibitor for the treatment of rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285764", "endSection": "title" }, { "offsetInBeginSection": 774, "offsetInEndSection": 876, "text": "Tofacitinib is the first oral Janus kinase inhibitor indicated for treatment of moderate to severe RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218541", "endSection": "title" }, { "offsetInBeginSection": 180, "offsetInEndSection": 434, "text": "The preclinical pharmacokinetic (PK)/pharmacodynamic (PD) profile of tofacitinib, an oral Janus kinase (JAK) inhibitor, in a mouse collagen-induced arthritis (mCIA) model was compared with clinical PK/PD data from patients with rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218541", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 430, "text": "With tofacitinib, the first Janus kinase (JAK) inhibitor has been approved in the USA, as well as in Switzerland and other countries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24193189", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 134, "text": "Tofacitinib, which is a Janus kinase (JAK) inhibitor, has shown clinical effects in the treatment of rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013646", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 625, "text": "Tofacitinib is an oral janus kinase (JAK) inhibitor that inhibits JAK family kinase members, in particular JAK1 and JAK3, achieving a broad limitation of inflammation by interfering with several cytokine receptors. It first proved its efficacy as an immunosuppressive regimen after renal transplantation, and was recently approved by the FDA for rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23627915", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1272, "text": " In patients treated with the JAK inhibitor tofacitinib, RR for hypercholesterolaemia was 1.70 (1.10 to 2.63) that was dose related. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23599436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "After two decades of research and development activity focussed on orally active kinase inhibitors, the first such drug (the JAK inhibitor Xeljanz, tofacitinib) was approved by the FDA in November 2012 for the treatment of rheumatoid arthritis (RA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "JAK inhibitor tofacitinib for treating rheumatoid arthritis: from basic to clinical.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212593", "endSection": "title" }, { "offsetInBeginSection": 317, "offsetInEndSection": 474, "text": "An orally available JAK3 inhibitor, tofacitinib, has been applied for RA, with satisfactory effects and acceptable safety in multiple clinical examinations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212593", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 935, "text": "Subsequently, multiple phase 3 studies were carried out, and tofacitinib with or without methotrexate (MTX) is efficacious and has a manageable safety profile in active RA patients who are MTX na\u00efve or show inadequate response to methotrexate (MTX-IR), disease-modifying antirheumatic drugs (DMARD)-IR, or tumor necrosis factor (TNF)-inhibitor-IR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212593", "endSection": "abstract" }, { "offsetInBeginSection": 1369, "offsetInEndSection": 1519, "text": "Taken together, an orally available kinase inhibitor tofacitinib targeting JAK-mediated signals would be expected to be a new option for RA treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212593", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 355, "text": "A non-selective JAK inhibitor, ruxolitinib, has recently been approved to treat myelofibrosis whereas tofacitinib is poised for approval to treat rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22971156", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1138, "text": "The recent disclosure of the clinical efficacy of a selective JAK1 inhibitor (GLPG-0634) in rheumatoid arthritis and detailed disclosure of the some potent and highly selective JAK1 inhibitors provide a clear stimulus for further activity in this area. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22971156", "endSection": "abstract" }, { "offsetInBeginSection": 1632, "offsetInEndSection": 1818, "text": "These results suggest that the JAK inhibitor tofacitinib suppresses osteoclast-mediated structural damage to arthritic joints, and this effect is secondary to decreased RANKL production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22899318", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1285, "text": "More recently, the Janus kinase (JAK) inhibitor tofacitinib has been evaluated as a potential new treatment option in RA and is awaiting approval.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777068", "endSection": "abstract" }, { "offsetInBeginSection": 1300, "offsetInEndSection": 1794, "text": "A total of 140 patients were randomised to tofacitinib 1, 3, 5, 10 mg or placebo twice daily and the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12, a primary end point, was significant for all tofacitinib treatment groups. Thus, an orally available tofacitinib in combination with MTX was efficacious and had a manageable safety profile. Tofacitinib at 5 and 10 mg twice a day appears suitable for further evaluation to optimise the treatment of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22460142", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1440, "text": "Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374445", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 539, "text": "Recently, CP-690,550 (tofacitinib), originally developed as a JAK3 inhibitor, has been shown to be effective in phase III clinical trials of rheumatoid arthritis and collagen-induced arthritis (CIA) models, but the precise mechanism of the effect, especially with respect to Th17 cells, is poorly understood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22252297", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 146, "text": " Tofacitinib (CP-690,550) is a novel JAK inhibitor that is currently in clinical trials for the treatment of rheumatoid arthritis (RA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147632", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 298, "text": "To compare the efficacy, safety, and tolerability of 6 dosages of oral tofacitinib (CP-690,550) with placebo for the treatment of active rheumatoid arthritis (RA) in patients receiving a stable background regimen of methotrexate (MTX) who have an inadequate response to MTX monotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22006202", "endSection": "abstract" }, { "offsetInBeginSection": 1724, "offsetInEndSection": 1930, "text": "In patients with active RA in whom the response to MTX has been inadequate, the addition of tofacitinib at a dosage \u22653 mg twice daily showed sustained efficacy and a manageable safety profile over 24 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22006202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "OBJECTIVE: To compare the efficacy, safety, and tolerability of 5 doses of oral tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response to disease-modifying antirheumatic drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21952978", "endSection": "abstract" }, { "offsetInBeginSection": 1749, "offsetInEndSection": 1913, "text": "Tofacitinib monotherapy at \u22653 mg twice a day was efficacious in the treatment of patients with active RA over 24 weeks and demonstrated a manageable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21952978", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 107, "text": "The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21884580", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 326, "text": "CP-690,550 is a potent and selective JAK inhibitor currently in clinical trials for rheumatoid arthritis (RA) and other autoimmune disease indications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20701804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Co-administration of the JAK inhibitor CP-690,550 and methotrexate is well tolerated in patients with rheumatoid arthritis without need for dose adjustment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20233177", "endSection": "title" }, { "offsetInBeginSection": 6, "offsetInEndSection": 369, "text": "To investigate the effects of methotrexate (MTX) on the pharmacokinetics (PK) of CP-690,550, a novel Janus kinase (JAK) inhibitor in development as a therapy for rheumatoid arthritis (RA), to determine the effects of multiple doses of CP-690,550 on the PK of MTX, and to evaluate the short-term safety and tolerability of co-administration of CP-690,550 and MTX. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20233177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19587388", "endSection": "title" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1101, "text": "CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19587388", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1730, "text": "Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19565475", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 578, "text": "INCB18424 targeting Jak1/2 and CP690,550 targeting Jak3 has been developed and is now on phase II clinical study for RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404006", "endSection": "abstract" } ] }, { "body": "Which is the mechanism used for synthesis of a highly functional N-truncated dystrophin isoform that attenuates dystrophinopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25108525" ], "ideal_answer": [ "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice", "Alternative translation initiation beginning in DMD exon 6 with the use of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible leads to expression of a highly functional N-truncated dystrophin isoform which is able to ameliorate disease severity.", "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice " ], "type": "summary", "id": "57167625cb4ef8864c000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "title" }, { "offsetInBeginSection": 149, "offsetInEndSection": 488, "text": "amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. Here we demonstrate that this isoform results from usage of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 543, "text": "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "title" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1412, "text": "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 341, "text": "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 1038, "text": "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 343, "text": "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 1040, "text": "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 342, "text": "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 1040, "text": "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 343, "text": "amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 343, "text": "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108525", "endSection": "title" } ] }, { "body": "Which are the newly identified DNA nucleases that can be used to treat thalassemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24305179", "http://www.ncbi.nlm.nih.gov/pubmed/24286287", "http://www.ncbi.nlm.nih.gov/pubmed/24323919", "http://www.ncbi.nlm.nih.gov/pubmed/24305403", "http://www.ncbi.nlm.nih.gov/pubmed/24299737", "http://www.ncbi.nlm.nih.gov/pubmed/24211574", "http://www.ncbi.nlm.nih.gov/pubmed/24155235", "http://www.ncbi.nlm.nih.gov/pubmed/24305278", "http://www.ncbi.nlm.nih.gov/pubmed/24157834", "http://www.ncbi.nlm.nih.gov/pubmed/24253446", "http://www.ncbi.nlm.nih.gov/pubmed/23408852", "http://www.ncbi.nlm.nih.gov/pubmed/21953455", "http://www.ncbi.nlm.nih.gov/pubmed/23002118", "http://www.ncbi.nlm.nih.gov/pubmed/24291598", "http://www.ncbi.nlm.nih.gov/pubmed/23386979" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/keywords/540", "o": "http://purl.uniprot.org/keywords/378" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/540", "o": "Nuclease" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/378", "o": "Hydrolase" }, { "p": "http://www.w3.org/2000/01/rdf-schema#seeAlso", "s": "http://purl.uniprot.org/keywords/540", "o": "http://purl.uniprot.org/go/0004518" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0004518", "o": "nuclease activity" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0004518", "o": "http://www.geneontology.org/go#GO:0004518" } ], "ideal_answer": [ "Thalassemia is genetic diseases of the blood caused by mutations in the globin gene. Main goal for thalassemia treatment is to develop homologous recombination based gene therapy in order to cure these diseases. Zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) are proper targets for the human globin gene. Genome editing using engineered nucleases such as ZFNs and TALENs has become a powerful technology for reverse genetics.", "The newly identified DNA nucleases that can be used to treat thalassemia are the transcription activator-like effector nucleases (TALEN). These are engineered proteins able to stimulate targeted integration of therapeutic wild-type beta-globin cDNAs to the endogenous beta-globin locus." ], "exact_answer": [ [ "TALEN", "Transcription activator-like effector nucleases" ], [ "Crispr/CAS" ], [ "zinc-finger nucleases" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004523", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008821", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032075", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004269", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013789", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015723", "http://www.disease-ontology.org/api/metadata/DOID:1099", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.uniprot.org/uniprot/NUCE_STRPN", "http://www.uniprot.org/uniprot/NUCA_BACSU", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064112", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064113", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064130", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017085", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017086", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004530", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032069", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059372", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004274", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004518", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032074", "http://www.uniprot.org/uniprot/NUC1_SYNRA", "http://www.uniprot.org/uniprot/NUCE_STRR6", "http://www.uniprot.org/uniprot/NUCA_NOSS1", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003851", "http://www.disease-ontology.org/api/metadata/DOID:10241", "http://www.disease-ontology.org/api/metadata/DOID:12241", "http://www.uniprot.org/uniprot/NUCA_SERMA" ], "type": "list", "id": "52d2818403868f1b06000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) DNA editing technology enables site-directed engineering of the genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24305278", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 792, "text": "We used this opportunity to evaluate the effect of total donor homology on transcription activator-like effector nuclease (TALEN) mediated bi-allelic modification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24305403", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 535, "text": "Herein we describe our applications of site-specific nucleases, especially transcription activator-like effector nucleases, to engineer specific alterations in the genomes of pigs and cows.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24305179", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 286, "text": "In this study, we used zinc finger nuclease-mediated knockout of the aryl hydrocarbon receptor (AHR) or AHR nuclear translocator (ARNT) in MCF7 and AHR knockout in MDA-MB-231 human breast cancer cells to investigate cross talk among AHR, ARNT, and estrogen receptor \u03b1 (ER\u03b1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24299737", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1005, "text": " For example, after binding DNA, TALEs fused to transcriptional activation domains can function as robust transcription factors (TALE-TFs), while fused to restriction endonucleases (TALENs) can cut DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291598", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 172, "text": "Genome editing using engineered nucleases such as transcription activator-like effector nucleases (TALENs) has become a powerful technology for reverse genetics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24286287", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 806, "text": "Here, we describe a robust process combining efficient generation of integration-free \u03b2-Thal iPSCs from the cells of patients and transcription activator-like effector nuclease (TALEN)-based universal correction of HBB mutations in situ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155235", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 723, "text": "We report here the correction of \u03b1-thalassemia major hydrops fetalis in transgene-free iPS cells using zinc finger-mediated insertion of a globin transgene in the AAVS1 site on human chromosome 19. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23002118", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 724, "text": " Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site-specific transcriptional repression or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24323919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "RNA-guided endonucleases (RGENs), derived from the prokaryotic adaptive immune system known as CRISPR/Cas, enable targeted genome engineering in cells and organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24253446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The CRISPR/Cas technology has been successfully used to stimulate the integration of small DNA sequences in a target locus to produce gene mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211574", "endSection": "abstract" } ] }, { "body": "Does ziconotide bind to N-type calcium channels?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11279062", "http://www.ncbi.nlm.nih.gov/pubmed/16831862", "http://www.ncbi.nlm.nih.gov/pubmed/16225359", "http://www.ncbi.nlm.nih.gov/pubmed/22608964", "http://www.ncbi.nlm.nih.gov/pubmed/20413151", "http://www.ncbi.nlm.nih.gov/pubmed/25456079", "http://www.ncbi.nlm.nih.gov/pubmed/10666532", "http://www.ncbi.nlm.nih.gov/pubmed/15578997", "http://www.ncbi.nlm.nih.gov/pubmed/16207099", "http://www.ncbi.nlm.nih.gov/pubmed/10834782", "http://www.ncbi.nlm.nih.gov/pubmed/20188724", "http://www.ncbi.nlm.nih.gov/pubmed/22084632", "http://www.ncbi.nlm.nih.gov/pubmed/17063978", "http://www.ncbi.nlm.nih.gov/pubmed/16845440", "http://www.ncbi.nlm.nih.gov/pubmed/11059665", "http://www.ncbi.nlm.nih.gov/pubmed/21577088", "http://www.ncbi.nlm.nih.gov/pubmed/10666519", "http://www.ncbi.nlm.nih.gov/pubmed/15209164", "http://www.ncbi.nlm.nih.gov/pubmed/9315745", "http://www.ncbi.nlm.nih.gov/pubmed/25446431", "http://www.ncbi.nlm.nih.gov/pubmed/22428804", "http://www.ncbi.nlm.nih.gov/pubmed/17199507", "http://www.ncbi.nlm.nih.gov/pubmed/10436454", "http://www.ncbi.nlm.nih.gov/pubmed/22188924", "http://www.ncbi.nlm.nih.gov/pubmed/21992243", "http://www.ncbi.nlm.nih.gov/pubmed/19300539", "http://www.ncbi.nlm.nih.gov/pubmed/10547097" ], "ideal_answer": [ "Yes, ziconotide/omega-conotoxin MVIIA blocks N-type calcium channels." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020864" ], "type": "yesno", "id": "56cf27293975bb303a000003", "snippets": [ { "offsetInBeginSection": 375, "offsetInEndSection": 749, "text": "Since this region partially overlaps with residues previously implicated in block of the channel by omega-conotoxin GVIA, we assessed the effects of mutations in the putative EF hand domain on channel block by omega-conotoxin GVIA and the structurally related omega-conotoxin MVIIA. Both of the toxins irreversibly block the activity of wild type alpha(1B) N-type channels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11279062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Despite their high sequence homology, the peptide neurotoxins omega-conotoxin MVIIA and MVIIC selectively block N- and P/Q-type calcium channels, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9315745", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 637, "text": " Binding assay for both N- and P/Q-type calcium channels showed that amino acid residues restricted to the N-terminal half are important for the recognition of N-type channels, whereas essential residues for P/Q-type channel recognition are widely spread over the whole omega-conotoxin molecule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9315745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Ziconotide is a novel peptide that blocks the entry of calcium into neuronal N-type voltage-sensitive calcium channels, preventing the conduction of nerve signals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16207099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Ziconotide is a selective, potent and reversible blocker of neuronal N-type voltage-sensitive calcium channels (VSCCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10666532", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 456, "text": "The therapeutic benefit of ziconotide derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16225359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10666532", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10834782", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16207099", "endSection": "title" }, { "offsetInBeginSection": 756, "offsetInEndSection": 854, "text": "Thus, ziconotide is the first of a new class of agents--N-type calcium channel blockers, or NCCBs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16225359", "endSection": "abstract" }, { "offsetInBeginSection": 1227, "offsetInEndSection": 1342, "text": "Ziconotide, formerly known also as SNX- 111, represents a new class of agents, the N-type calcium channel blockers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16845440", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 419, "text": "The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25456079", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 594, "text": "A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16831862", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1292, "text": "As the clinically available analgesics, pregabalin (alpha2delta-subunit calcium channel ligand), ziconotide (N-type calcium channel blocker), mexiletine (sodium channel blocker), and duloxetine (serotonin and norepinephrine reuptake inhibitors) were evaluated in these neurochemically-induced allodynia models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20188724", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 626, "text": "The present investigation was designed to assess the safety and analgesic efficacy of ziconotide, a new N-type calcium channel blocker, when administered intrathecally to patients with acute postoperative pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10834782", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 588, "text": "Inhibition of the N-type calcium channel by intrathecal administration of the channel-specific blocker omega-conotoxin MVIIA (ziconotide) is efficacious in the treatment of severe chronic pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17199507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Ziconotide is a powerful analgesic drug that has a unique mechanism of action involving potent and selective block of N-type calcium channels, which control neurotransmission at many synapses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19300539", "endSection": "abstract" }, { "offsetInBeginSection": 1924, "offsetInEndSection": 2212, "text": "In conclusion, present findings provide implication that the spinal anti-nociceptive mechanistic site of pregabalin is different from that of ziconotide, mexiletine, and duloxetine, and pregabalin could have a broader anti-nociceptive mechanism other than N-type calcium channel blockade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20188724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive calcium channels, is antinociceptive when it is administered intrathecally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10666519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10666519", "endSection": "title" }, { "offsetInBeginSection": 142, "offsetInEndSection": 288, "text": "A state-dependent Ca(V)2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl Ca(V)2.2 inhibitor used clinically. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22188924", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 273, "text": "There is also human validation data from ziconotide, the CaV2.2-selective peptidyl inhibitor used clinically to treat refractory pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25446431", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 432, "text": "A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16831862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10436454", "endSection": "title" } ] }, { "body": "How is OCT3 associated with serotonin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "http://www.ncbi.nlm.nih.gov/pubmed/19033200", "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "http://www.ncbi.nlm.nih.gov/pubmed/19025979", "http://www.ncbi.nlm.nih.gov/pubmed/21636115", "http://www.ncbi.nlm.nih.gov/pubmed/24618127", "http://www.ncbi.nlm.nih.gov/pubmed/24246570", "http://www.ncbi.nlm.nih.gov/pubmed/23982114", "http://www.ncbi.nlm.nih.gov/pubmed/12584728", "http://www.ncbi.nlm.nih.gov/pubmed/19371745" ], "ideal_answer": [ "OCT3 plays a role in serotonin clearance" ], "exact_answer": [ "serotonin clearance" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012701", "http://www.biosemantics.org/jochem#4274509", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4274509", "http://www.uniprot.org/uniprot/OCT3_ARATH" ], "type": "factoid", "id": "571e2beabb137a4b0c000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "The organic cation transporter 3 (OCT3) is a widely expressed transporter for endogenous and exogenous organic cations. Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982114", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 959, "text": "Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 413, "text": "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982114", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1152, "text": "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates bidirectional, sodium-independent transport of dopamine, norepinephrine, epinephrine, serotonin, and histamine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19025979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "The effect of blockade of either 5-hydroxytryptamine (5-HT)/serotonin transporter (SERT) with citalopram or the organic cation transporter 3 (OCT3)/plasma membrane monoamine transporter (PMAT) with decynium-22 (D-22) on spontaneous and evoked release of 5-HT in the nucleus tractus solitarius (NTS) was investigated in rat brainstem slices treated with gabazine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24618127", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 266, "text": "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982114", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 993, "text": "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 764, "text": "Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates bidirectional, sodium-independent transport of dopamine, norepinephrine, epinephrine, serotonin, and histamine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19025979", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1386, "text": "RESULTS: We found a drastic decrease in IL-4 production by stimulated basophils on exposure to serotonin (5-hydroxytryptamine [5-HT]) that is taken up by basophils through the specific high-affinity transporters serotonin transporter and the polyspecific, high-capacity organic cation transporter 3 (OCT3; or Slc22a3) but inhibits their function exclusively through the latter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21636115", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 268, "text": "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982114", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 995, "text": "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19033200", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Organic cation transporter capable of transporting serotonin is up-regulated in serotonin transporter-deficient mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12584728", "endSection": "title" }, { "offsetInBeginSection": 568, "offsetInEndSection": 766, "text": "Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 268, "text": "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982114", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 995, "text": "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1345, "text": "We found a drastic decrease in IL-4 production by stimulated basophils on exposure to serotonin (5-hydroxytryptamine [5-HT]) that is taken up by basophils through the specific high-affinity transporters serotonin transporter and the polyspecific, high-capacity organic cation transporter 3 (OCT3; or Slc22a3) but inhibits their function exclusively through the latter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21636115", "endSection": "abstract" } ] }, { "body": "What constitutes an increased risk for individuals with Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22965917", "http://www.ncbi.nlm.nih.gov/pubmed/24259538", "http://www.ncbi.nlm.nih.gov/pubmed/1084238", "http://www.ncbi.nlm.nih.gov/pubmed/10994546", "http://www.ncbi.nlm.nih.gov/pubmed/21279724", "http://www.ncbi.nlm.nih.gov/pubmed/21355096", "http://www.ncbi.nlm.nih.gov/pubmed/22504776", "http://www.ncbi.nlm.nih.gov/pubmed/21131752", "http://www.ncbi.nlm.nih.gov/pubmed/21109493", "http://www.ncbi.nlm.nih.gov/pubmed/12750283", "http://www.ncbi.nlm.nih.gov/pubmed/18786261", "http://www.ncbi.nlm.nih.gov/pubmed/17909071", "http://www.ncbi.nlm.nih.gov/pubmed/22937327", "http://www.ncbi.nlm.nih.gov/pubmed/12354784", "http://www.ncbi.nlm.nih.gov/pubmed/19728769", "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "http://www.ncbi.nlm.nih.gov/pubmed/12685843", "http://www.ncbi.nlm.nih.gov/pubmed/23146055" ], "ideal_answer": [ "Fanconi anemia is a rare genetic disorder associated with an increased risk of leukemias and solid tumors." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "summary", "id": "54ede5a494afd61504000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Fanconi anemia (FA) is a rare autosomal recessive disease characterized by a greatly increased risk of cancer among those diagnosed with the syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17909071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Fanconi anaemia (FA) is an inherited condition characterised by congenital and developmental abnormalities and a strong cancer predisposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair. Major clinical problems in FA include congenital abnormalities, endocrinopathies, early onset bone marrow failure and increased risk of myelodysplastic syndrome, acute leukemia and solid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Fanconi anemia is associated with an increased risk of malignancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22937327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, congenital abnormalities, and an increased risk for cancer and leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21355096", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 261, "text": "Fanconi anemia (FA) is an autosomal recessive, cancer susceptibility disorder characterized by diverse clinical features, such as short stature, skeletal or skin abnormalities, progressive bone marrow (BM) failure, and increased risk of malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21131752", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1457, "text": "The FA patients have a high risk of developing malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21131752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Fanconi anemia (FA) is an autosomal recessive DNA repair disorder with affected individuals having a high risk of developing acute myeloid leukaemia and certain solid tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18786261", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1193, "text": "In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure, increased cancer risk and hypersensitivity to DNA cross-linking agents, implying a role for this pathway in the maintenance of genomic stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by bone marrow failure and increased risk of cancers including acute myelogenous leukemia and various solid tumors, especially head and neck cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22965917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Fanconi anemia (FA) is a rare recessive DNA repair disorder that is clinically characterized by congenital malformations, progressive bone marrow failure, and increased incidence of malignancies, especially acute myeloid leukemia and squamous cell carcinomas of the head and neck (HNSCCs) and the anogenital regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504776", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1205, "text": "In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279724", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 437, "text": "FA is one of a group of recessive syndromes characterized by excessive spontaneous chromosomal breakage in which heterozygote carriers appear to display an increased risk of cancer and there is some indirect evidence that FA carriers may also be at increased risk of AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12685843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Mutations in Fanconi anemia genes and the risk of esophageal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279724", "endSection": "title" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1271, "text": "The co-occurrence of brain tumors, Fanconi anemia, and breast cancer observed in one of these kindreds constitutes a new syndromic association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Fanconi anemia is a genetically heterogeneous disorder associated with chromosome instability and a highly elevated risk for developing cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728769", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 407, "text": "BRCA2 is an FA gene and additionally conveys an inherited risk for breast, ovarian, and pancreatic cancer for individuals carrying a single mutated allele [N. G. Howlett et al., Science (Wash. DC), 297: 606-609, 2002]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12750283", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 165, "text": "Around 10-15% of individuals with recessively inherited Fanconi anaemia (FA) develop AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12685843", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1270, "text": "The co-occurrence of brain tumors, Fanconi anemia, and breast cancer observed in one of these kindreds constitutes a new syndromic association", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 565, "text": "It is postulated that both T and B cells could be involved in the development of leukemia in Fanconi's anemia patients, assuming that chromosome breaks constitute a factor predisposing to the development of malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1084238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Patients with Fanconi Anemia (FANC) have a well documented increased risk to develop malignancies, especially Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10994546", "endSection": "abstract" }, { "offsetInBeginSection": 1890, "offsetInEndSection": 2032, "text": "The findings within this family support the hypothesis of an increased risk to develop malignancies in heterozygous carriers of FANC-mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10994546", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 436, "text": "FA is one of a group of recessive syndromes characterized by excessive spontaneous chromosomal breakage in which heterozygote carriers appear to display an increased risk of cancer and there is some indirect evidence that FA carriers may also be at increased risk of AML", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12685843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Fanconi anemia (FA) is a rare autosomal recessive disease characterized by skeletal defects, anemia, chromosomal instability and increased risk of leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12354784", "endSection": "abstract" } ] }, { "body": "Is stop codon bypass possible?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17961216", "http://www.ncbi.nlm.nih.gov/pubmed/2010914", "http://www.ncbi.nlm.nih.gov/pubmed/21969101", "http://www.ncbi.nlm.nih.gov/pubmed/18809619", "http://www.ncbi.nlm.nih.gov/pubmed/23083810", "http://www.ncbi.nlm.nih.gov/pubmed/17187982", 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"http://purl.uniprot.org/uniprot/Q08280", "o": "http://purl.uniprot.org/citations/14562095" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/14562095", "o": "http://purl.uniprot.org/medline/22923954" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/14562095", "o": "Nature" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/14562095", "o": "http://purl.uniprot.org/pubmed/14562095" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/Q08280", "o": "http://purl.uniprot.org/citations/14562106" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/14562106", "o": "http://purl.uniprot.org/pubmed/14562106" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/14562106", "o": "Nature" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/14562106", "o": "http://purl.uniprot.org/medline/22923965" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/Q08280", "o": "http://purl.uniprot.org/citations/9169874" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/9169874", "o": "Nature" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/9169874", "o": "http://purl.uniprot.org/pubmed/9169874" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/9169874", "o": "http://purl.uniprot.org/medline/97313270" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q12140", "o": "true" }, { "p": "http://linkedlifedata.com/resource/relationontology/binding", "s": "http://purl.uniprot.org/uniprot/Q12140", "o": "http://purl.uniprot.org/uniprot/P38822" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5033383832320012", "o": "Protein BZZ1" } ], "ideal_answer": [ "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC.\nAminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT).\nExpression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift).", "Yes it is. The UGA stop codon was found to code for seleno-cysteine in a number of Saccharomyces cerevisiae genes, whereas the UAG stop codon was shown to code for pyrro-lysine in some archaean species. Moreover, in experimental and therapeutic settings, aminoglycoside-induced stop codon bypass has been used to restore protein translation by promoting readthrough of stop codons, generated by mutations causing premature termination of protein synthesis. Additionally, cytosine deamination to uracil in stop codons may result in stop codon bypass, whereas in a number of polycistronic genes or sequential ORFs, there is evidence for stop codon bypass, although their induction mechanisms are still unclear. Additional hypotheses for stop codon bypass involve the 3' context of the translated transcript, non-conventional anticodon-codon interactions or translational frameshifts." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/BSC1_YEAST", "http://www.uniprot.org/uniprot/BSC6_YEAST", "http://www.uniprot.org/uniprot/BSC2_YEAST", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018388", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003062", "http://www.uniprot.org/uniprot/BSC5_YEAST", "http://www.uniprot.org/uniprot/BSC4_YEAST", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018387" ], "type": "yesno", "id": "52f77f892059c6d71c00002c", "snippets": [ { "offsetInBeginSection": 275, "offsetInEndSection": 492, "text": "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17881586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Expression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22718819", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 426, "text": "Recent studies on translation termination in the yeast Saccharomyces cerevisiae have not only enabled the identification of the key components of the termination machinery, but have also revealed several regulatory mechanisms that might enable the controlled synthesis of C-terminally extended polypeptides via stop-codon readthrough. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17187982", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1124, "text": "The effects of all possible single-base mutations in the codons flanking the stop indicated that 3' contexts of the form CAR-YYA confer leakiness and that the 3' context permits read through of UAA and UGA stop codons as well as UAG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2010914", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 362, "text": "As a first step to elucidate the mechanism(s) by which ribosomes bypass leaky stop codons in vivo, we have devised a system in which readthrough is coupled to the transient expression of beta-glucuronidase (GUS) in tobacco protoplasts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2103444", "endSection": "abstract" } ] }, { "body": "Is the protein \u03b21-integrin recycled?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23264734", "http://www.ncbi.nlm.nih.gov/pubmed/22454518", "http://www.ncbi.nlm.nih.gov/pubmed/23139422", "http://www.ncbi.nlm.nih.gov/pubmed/24887021", "http://www.ncbi.nlm.nih.gov/pubmed/25344254", "http://www.ncbi.nlm.nih.gov/pubmed/26256210", "http://www.ncbi.nlm.nih.gov/pubmed/23839032", "http://www.ncbi.nlm.nih.gov/pubmed/24036548", "http://www.ncbi.nlm.nih.gov/pubmed/24719112", "http://www.ncbi.nlm.nih.gov/pubmed/22561348", "http://www.ncbi.nlm.nih.gov/pubmed/22222055" ], "ideal_answer": [ "Yes, the \u03b21-integrin is recycled." ], "exact_answer": "yes", "type": "yesno", "id": "56e5b445edfc094c1f000001", "snippets": [ { "offsetInBeginSection": 87, "offsetInEndSection": 190, "text": "Pathways selectively regulating \u03b21-integrin recycling are implicated in cancer invasion and metastasis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26256210", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 629, "text": "integrin-positive early and recycling endosomes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24719112", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 847, "text": "LPA-induced recycling of \u03b21 integrin,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25344254", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 391, "text": "RCP-mediated recycling of \u03b15\u03b21 integrin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24887021", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 838, "text": "CycD1 overexpression increased \u03b21 integrin recycling ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23839032", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1092, "text": "inhibition of autophagy slowed down the lysosomal degradation of internalized \u03b21 integrins and promoted its membrane recycling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24036548", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 460, "text": "recycling pathway for \u03b21-integrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23264734", "endSection": "abstract" }, { "offsetInBeginSection": 65, "offsetInEndSection": 87, "text": " \u03b21 integrin recycling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454518", "endSection": "title" }, { "offsetInBeginSection": 561, "offsetInEndSection": 583, "text": " \u03b21 integrin recycling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454518", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 390, "text": " controlling \u03b21 integrin recycling to the plasma membrane ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23139422", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 712, "text": "integrin recycling pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23139422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Distinct recycling of active and inactive \u03b21 integrins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22222055", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Integrin functions are controlled by regulating their affinity for ligand, and by the efficient recycling of intact integrins through endosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561348", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 934, "text": " \u03b21 integrins, resulting in their recycling to the cell surface where they can be reused.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561348", "endSection": "abstract" } ] }, { "body": "Are BBS mutations involved in syndromic Hirschsprung disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19666486" ], "ideal_answer": [ "In 3 families with Bardet-Biedl syndrome (BBS) and Hirschsprung disease (HSCR), concomitant mutations in BBS genes and regulatory RET elements have been identified. Analysis of the data suggests that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10487" ], "type": "yesno", "id": "55032179e9bde6963400002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666486", "endSection": "title" }, { "offsetInBeginSection": 341, "offsetInEndSection": 656, "text": "Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666486", "endSection": "title" }, { "offsetInBeginSection": 521, "offsetInEndSection": 657, "text": "Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666486", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 518, "text": "Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666486", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 655, "text": "Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666486", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 519, "text": "Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666486", "endSection": "abstract" } ] }, { "body": "Which signaling pathway is activating the dishevelled proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25358879", "http://www.ncbi.nlm.nih.gov/pubmed/15936275", "http://www.ncbi.nlm.nih.gov/pubmed/19561403" ], "ideal_answer": [ "Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling" ], "exact_answer": [ "Wnt signaling" ], "type": "factoid", "id": "5708a845cf1c32585100000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Wnt signaling is known to be important for diverse embryonic and post-natal cellular events and be regulated by the proteins Dishevelled and Axin. Although Dishevelled is activated by Wnt and involved in signal transduction, it is not clear how Dishevelled-mediated signaling is turned off. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The Dishevelled protein mediates several diverse biological processes. Intriguingly, within the same tissues where Xenopus Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15936275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25358879", "endSection": "abstract" } ] }, { "body": "Which is the defective protein causing the lysosomal storage disease Fabry?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19202000", "http://www.ncbi.nlm.nih.gov/pubmed/9323559", "http://www.ncbi.nlm.nih.gov/pubmed/15533650", "http://www.ncbi.nlm.nih.gov/pubmed/19146893", "http://www.ncbi.nlm.nih.gov/pubmed/15702403", "http://www.ncbi.nlm.nih.gov/pubmed/9395081" ], "ideal_answer": [ "Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme." ], "exact_answer": [ "alpha-galactosidase A" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008247", "http://www.disease-ontology.org/api/metadata/DOID:3211", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016464", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005764", "http://www.disease-ontology.org/api/metadata/DOID:14499", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000795" ], "type": "factoid", "id": "51405cd123fec90375000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "The lysosomal storage disorder Fabry disease is characterized by excessive globotriaosylceramide (Gb3) accumulation in major organs such as the heart and kidney. Defective lysosomal alpha-galactosidase A (Gla) is responsible for excessive Gb3 accumulation, and one cell sensitive to the effects of Gb3 accumulation is vascular endothelium.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19202000", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15702403", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Human alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A) is the lysosomal exoglycosidase responsible for the hydrolysis of terminal alpha-galactosyl residues from glycoconjugates and is the defective enzyme causing Fabry disease (McKusick 301500).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9323559", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Transgenic mice expressing a human mutant alpha-galactosidase with an R301Q substitution, which was found in a patient with a variant form of Fabry disease, were established.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9395081", "endSection": "sections.0" } ] }, { "body": "Is there any software for automated analysis of immuno-histochemistry images?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21818782", "http://www.ncbi.nlm.nih.gov/pubmed/23625497", "http://www.ncbi.nlm.nih.gov/pubmed/22114700", "http://www.ncbi.nlm.nih.gov/pubmed/20663194", "http://www.ncbi.nlm.nih.gov/pubmed/20588996", "http://www.ncbi.nlm.nih.gov/pubmed/24003130", "http://www.ncbi.nlm.nih.gov/pubmed/23586030", "http://www.ncbi.nlm.nih.gov/pubmed/24262147" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2864120", "o": "NJW" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2864120", "o": "CONTROL MATERIAL, HER-2/NEU, IMMUNOHISTOCHEMISTRY" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1262352", "o": "http://linkedlifedata.com/resource/umls/label/A2864120" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17697331", "o": "C82988" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17697331", "o": "S-100 Immunohistochemistry Staining Method" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2826611", "o": "http://linkedlifedata.com/resource/umls/label/A17697331" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2864179", "o": "NJT" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2864179", "o": "IMMUNOHISTOCHEMISTRY REAGENTS AND KITS" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1262349", "o": "http://linkedlifedata.com/resource/umls/label/A2864179" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11967491", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11967491", "o": "Peripheral and cytoplasmic desmoplakin staining (immunohistochemistry) ELECTRON MICROSCOPY:" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1843296", "o": "http://linkedlifedata.com/resource/umls/label/A11967491" } ], "ideal_answer": [ "In some studies of breast cancer, quantitation of immunohistochemically highlighted microvessel \u2018hot spots\u2019 has been shown to be a powerful prognostic tool. However, the antibody used, the number and size of the \u2018hot spots\u2019 assessed, and the stratification of patients into high and low vascular groups vary between studies. Furthermore, little is known about the relationship between microvessel density and other vascular parameters. These uncertainties and the laborious nature of the technique make it unsuitable for diagnostic practice. Both manual and computerized image analysis techniques were used in this study to examine the relationship between microvessel density and the vascular parameters in different sized microscopic fields in a pilot series of 30 invasive breast carcinomas. Automated pixel analysis of immunohistochemical staining, Chalkley point counting, and observer subjective vascular grading were also assessed as more rapid methods of measuring tumour vascularity" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007150", "http://www.uniprot.org/uniprot/HCP_ECOSE", "http://www.uniprot.org/uniprot/GFP_AEQVI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017403", "http://www.uniprot.org/uniprot/HCP_CLOB1", "http://www.disease-ontology.org/api/metadata/DOID:4943", "http://www.uniprot.org/uniprot/HCP_ENT38", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005453" ], "type": "yesno", "id": "5311ceeae3eabad021000008", "snippets": [ { "offsetInBeginSection": 164, "offsetInEndSection": 466, "text": "The LIM homeobox gene Lhx2 is expressed in cortical progenitors during development and also in the superficial layers of the neocortex in maturity. However, analysis of Lhx2 function at later stages of cortical development has been hampered by severe phenotypes associated with early loss of function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24262147", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 695, "text": "The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23586030", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 619, "text": "Tissue Transglutaminase (TG2) is a multifunctional enzyme, which amongst other functions, is involved in cell differentiation. Therefore, we hypothesized that TG2 contributes to differentiation of OPCs into OLGs and thereby stimulates remyelination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21818782", "endSection": "abstract" } ] }, { "body": "Is TALEN being used on stem cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24305178", "http://www.ncbi.nlm.nih.gov/pubmed/24206569", "http://www.ncbi.nlm.nih.gov/pubmed/25245091", "http://www.ncbi.nlm.nih.gov/pubmed/25408877", "http://www.ncbi.nlm.nih.gov/pubmed/24155235", "http://www.ncbi.nlm.nih.gov/pubmed/24319658", "http://www.ncbi.nlm.nih.gov/pubmed/24691488", "http://www.ncbi.nlm.nih.gov/pubmed/25047178", "http://www.ncbi.nlm.nih.gov/pubmed/26052525", "http://www.ncbi.nlm.nih.gov/pubmed/23246482", "http://www.ncbi.nlm.nih.gov/pubmed/24996167", "http://www.ncbi.nlm.nih.gov/pubmed/23666012", "http://www.ncbi.nlm.nih.gov/pubmed/23928856", "http://www.ncbi.nlm.nih.gov/pubmed/25434822", "http://www.ncbi.nlm.nih.gov/pubmed/25414332", "http://www.ncbi.nlm.nih.gov/pubmed/23921522", "http://www.ncbi.nlm.nih.gov/pubmed/23945944", "http://www.ncbi.nlm.nih.gov/pubmed/21738127", "http://www.ncbi.nlm.nih.gov/pubmed/22749015" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0036575", "o": "D013234" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0119455", "o": "D013234" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0036467", "o": "D013234" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0119446", "o": "D013234" } ], "ideal_answer": [ "Yes, TALEN is being used on stem cells for genome editing." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013234", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ], "type": "yesno", "id": "56f555b609dd18d46b000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434822", "endSection": "title" }, { "offsetInBeginSection": 119, "offsetInEndSection": 323, "text": "Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434822", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 392, "text": "We generated helper-dependent, capsid-modified adenovirus (HD-Ad5/35) vectors for zinc-finger nuclease (ZFN)- or transcription activator-like effector nuclease (TALEN)-mediated genome editing in human CD34+ hematopoietic stem cells (HSCs) from mobilized adult donors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052525", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 564, "text": "We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free \u03b2-thalassemia induced pluripotent stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155235", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "A TALEN genome-editing system for generating human stem cell-based disease models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23246482", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24996167", "endSection": "title" }, { "offsetInBeginSection": 623, "offsetInEndSection": 820, "text": "Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24996167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "A modified TALEN-based system for robust generation of knock-out human pluripotent stem cell lines and disease models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24206569", "endSection": "title" }, { "offsetInBeginSection": 464, "offsetInEndSection": 558, "text": "In this study, we utilized a cell-penetrating peptide-based system for ZFN and TALEN delivery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25408877", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 650, "text": "At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21738127", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 753, "text": "We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23246482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) have been successfully used to knock out endogenous genes in stem cell research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25408877", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 682, "text": "Here we report different methods to efficiently perform TALEN-mediated gene integration and inactivation in different mammalian cell systems including induced pluripotent stem cells and delineate experimental examples associated with these approaches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25047178", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1163, "text": "Together, our results demonstrate that TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA clusters in somatic cells and pluripotent stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24319658", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 474, "text": "We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23246482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25245091", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Baculoviral transduction facilitates TALEN-mediated targeted transgene integration and Cre/LoxP cassette exchange in human-induced pluripotent stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945944", "endSection": "title" }, { "offsetInBeginSection": 125, "offsetInEndSection": 346, "text": "We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666012", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 626, "text": "Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24996167", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1246, "text": "A 5% modification rate was observed in human induced pluripotent stem cells (hiPSCs) treated with TAT-TALEN as measured by the Surveyor assay. TAT-TALEN protein-mediated gene disruption was applicable in hiPSCs and represents a promising technique for gene knockout in stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25408877", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 474, "text": "Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21738127", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928856", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 698, "text": "At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21738127", "endSection": "abstract" } ] }, { "body": "Is there an association between bruxism and reflux", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15520695", "http://www.ncbi.nlm.nih.gov/pubmed/19089153", "http://www.ncbi.nlm.nih.gov/pubmed/23738993", "http://www.ncbi.nlm.nih.gov/pubmed/23937680", "http://www.ncbi.nlm.nih.gov/pubmed/24011800", "http://www.ncbi.nlm.nih.gov/pubmed/14655925", "http://www.ncbi.nlm.nih.gov/pubmed/21248360", "http://www.ncbi.nlm.nih.gov/pubmed/19830044" ], "ideal_answer": [ "There is an association between bruxism and reflux." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057045", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004942", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020186", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005764", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002012" ], "type": "yesno", "id": "52f8a7eb2059c6d71c000052", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 326, "text": "Rhythmic masticatory muscle activity, including sleep bruxism (SB), can be induced in healthy individuals by experimental esophageal acidification, which plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). However, no robust evidence supports the association between SB and GERD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24011800", "endSection": "abstract" }, { "offsetInBeginSection": 1564, "offsetInEndSection": 1647, "text": "Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24011800", "endSection": "abstract" }, { "offsetInBeginSection": 1471, "offsetInEndSection": 1670, "text": "Our large-scale cross-sectional study found that problem behaviors in adolescents were associated with sleep problems, including sleep bruxism, as well as lifestyle and food habits and GERD symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23937680", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 741, "text": "The frequencies of EMG bursts, rhythmic masticatory muscle activity (RMMA) episodes, grinding noise, and the RMMA/microarousal ratio were significantly higher in the 20-minute period after acidic infusion than after saline infusion. RMMA episodes including SB were induced by esophageal acidification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21248360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Direct restorative treatment of dental erosion caused by gastroesophageal reflux disease associated with bruxism:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738993", "endSection": "title" }, { "offsetInBeginSection": 338, "offsetInEndSection": 480, "text": "This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Dental wear caused by association between bruxism and gastroesophageal reflux disease:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19089153", "endSection": "title" }, { "offsetInBeginSection": 699, "offsetInEndSection": 909, "text": "This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19089153", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 988, "text": "most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Association between nocturnal bruxism and gastroesophageal reflux.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14655925", "endSection": "title" }, { "offsetInBeginSection": 2192, "offsetInEndSection": 2328, "text": "Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14655925", "endSection": "abstract" } ] }, { "body": "what is the role of IGF-1 in cardiac regeneration after myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22403243", "http://www.ncbi.nlm.nih.gov/pubmed/21546606", "http://www.ncbi.nlm.nih.gov/pubmed/15951423", "http://www.ncbi.nlm.nih.gov/pubmed/9329962", "http://www.ncbi.nlm.nih.gov/pubmed/17525368", "http://www.ncbi.nlm.nih.gov/pubmed/16141414", "http://www.ncbi.nlm.nih.gov/pubmed/19704095", "http://www.ncbi.nlm.nih.gov/pubmed/17805990", "http://www.ncbi.nlm.nih.gov/pubmed/21723061", "http://www.ncbi.nlm.nih.gov/pubmed/22590612", "http://www.ncbi.nlm.nih.gov/pubmed/20607468", "http://www.ncbi.nlm.nih.gov/pubmed/18948617", "http://www.ncbi.nlm.nih.gov/pubmed/18556576", "http://www.ncbi.nlm.nih.gov/pubmed/17045939", "http://www.ncbi.nlm.nih.gov/pubmed/21621517", "http://www.ncbi.nlm.nih.gov/pubmed/16698918", "http://www.ncbi.nlm.nih.gov/pubmed/20889201" ], "ideal_answer": [ "Ischemia-reperfusion injury is a strong stimulus for both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of IGF-1. Furthermore, in an animal model of myocardial infarction, intracoronary administration of IGF-1 is shown to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function. IGF-1 is a potent modulator of stem cell replication, commitment to the myocyte lineage, and myocyte differentiation. In another study, the dual delivery of IGF-1 and HGF from affinity-binding alginate biomaterial prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry and increased the incidence of GATA-4-positive cell clusters. The addition of nanofiber-mediated IGF-1 delivery to Cardiac Progenitor Cells therapy improved in part the recovery of myocardial structure and function after infarction. IGF-1 promotes proliferation and survival of CPCs. The strategy of IGF-1 transgene expression has shown to induce massive stem cell mobilization via SDF-1alpha signaling and culminated in extensive angiomyogenesis in the infarcted heart." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007334" ], "type": "summary", "id": "52f385052059c6d71c000011", "snippets": [ { "offsetInBeginSection": 1528, "offsetInEndSection": 1966, "text": "In conclusion, ischemia-reperfusion injury was the strongest stimulus with both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of the growth factors IGF-1 and HGF. Also pregnancy induced a general up-regulation of c-Kit and early Nkx2.5+ cardiomyocytes throughout the heart. Utilization of these pathways could provide new strategies for the treatment of cardiac disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22590612", "endSection": "abstract" }, { "offsetInBeginSection": 1312, "offsetInEndSection": 1570, "text": "Together, our data demonstrate that the paracrine regulation of cardiac miRNAs by transplanted BMCs contributes to the protective effects of cell therapy. BMCs release IGF-1, which inhibits the processing of miR-34a, thereby blocking cardiomyocyte apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403243", "endSection": "abstract" }, { "offsetInBeginSection": 1737, "offsetInEndSection": 1982, "text": "In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21723061", "endSection": "abstract" }, { "offsetInBeginSection": 1487, "offsetInEndSection": 1770, "text": "hCSCs expressing only IGF-1R synthesize both IGF-1 and IGF-2, which are potent modulators of stem cell replication, commitment to the myocyte lineage, and myocyte differentiation, which points to this hCSC subset as the ideal candidate cell for the management of human heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21546606", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 699, "text": "In physiologic conditions, cardiac overexpression of the IGF-1Ea propeptide is associated with an enrichment of c-Kit/Sca-1 positive side population cells in the bone marrow and the occurrence of an endothelial-primed CD34 positive side population in the heart. This cellular profile is shown here to correlate with the expression of cytokines involved in stem cell mobilization and vessel formation. This molecular and cellular interplay favored IGF-1Ea-mediated vessel formation in injured hearts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21621517", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1547, "text": "Furthermore, this treatment prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry and increased the incidence of GATA-4-positive cell clusters. The dual delivery of IGF-1 and HGF from affinity-binding alginate biomaterial represents a useful strategy to treat MI. It showed a marked therapeutic efficacy at various tissue levels, as well as potential to induce endogenous regeneration of cardiac muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20889201", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1284, "text": "Finally, neuregulins and periostin are proteins that induce cell-cycle reentry of cardiomyocytes, and growth factors like IGF-1 can induce growth and differentiation of stem cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20607468", "endSection": "abstract" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1703, "text": "The addition of nanofiber-mediated IGF-1 delivery to CPC therapy improved in part the recovery of myocardial structure and function after infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704095", "endSection": "abstract" }, { "offsetInBeginSection": 1780, "offsetInEndSection": 1969, "text": "In conclusion, the strategy of IGF-1 transgene expression induced massive stem cell mobilization via SDF-1alpha signaling and culminated in extensive angiomyogenesis in the infarcted heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18948617", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 724, "text": "We tested whether cardiac progenitor cells (CPCs) implanted in proximity of healed infarcts or resident CPCs stimulated locally by hepatocyte growth factor and insulin-like growth factor-1 invade the scarred myocardium and generate myocytes and coronary vessels improving the hemodynamics of the infarcted heart. Hepatocyte growth factor is a powerful chemoattractant of CPCs, and insulin-like growth factor-1 promotes their proliferation and survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18556576", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1689, "text": "Alternatively, growth factors may be delivered locally to stimulate resident CPCs and promote myocardial regeneration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18556576", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 735, "text": "supplemental mIGF-1 expression did not perturb normal cardiac growth and physiology. Restoration of cardiac function in post-infarct mIGF-1 transgenic mice was facilitated by modulation of the inflammatory response and increased antiapoptotic signaling. mIGF-1 ventricular tissue exhibited increased proliferative activity several weeks after injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Cardiac stem cells and early committed cells (CSCs-ECCs) express c-Met and insulin-like growth factor-1 (IGF-1) receptors and synthesize and secrete the corresponding ligands, hepatocyte growth factor (HGF) and IGF-1. HGF mobilizes CSCs-ECCs and IGF-1 promotes their survival and proliferation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16141414", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 932, "text": "After infarction, HGF and IGF-1 were injected intramyocardially to stimulate resident cardiac progenitor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951423", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1793, "text": "These results suggest that strategies capable of activating the growth reserve of the myocardium may be important in cardiac repair after ischemic injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951423", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1469, "text": "In conclusion, constitutive overexpression of IGF-1 prevented activation of cell death in the viable myocardium after infarction, limiting ventricular dilation, myocardial loading, and cardiac hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9329962", "endSection": "abstract" } ] }, { "body": "What is known about prostate cancer screening in the UK", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11495383", "http://www.ncbi.nlm.nih.gov/pubmed/20507844", "http://www.ncbi.nlm.nih.gov/pubmed/20840664", "http://www.ncbi.nlm.nih.gov/pubmed/19904272", "http://www.ncbi.nlm.nih.gov/pubmed/19671770", "http://www.ncbi.nlm.nih.gov/pubmed/20060331", "http://www.ncbi.nlm.nih.gov/pubmed/17826892", "http://www.ncbi.nlm.nih.gov/pubmed/23728749" ], "ideal_answer": [ "Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. Two systematic reviews have concluded that screening should not be carried out. In general, this recommendation has been accepted in the United Kingdom." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011471", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006113", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055088" ], "type": "summary", "id": "52f88a062059c6d71c000032", "snippets": [ { "offsetInBeginSection": 1208, "offsetInEndSection": 1367, "text": "Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19904272", "endSection": "abstract" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1808, "text": "The vast majority of citizens in nine European countries systematically overestimate the benefits of mammography and PSA screening. In the countries investigated, physicians and other information sources appear to have little impact on improving citizens' perceptions of these benefits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19671770", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1430, "text": "National systematic prostate cancer screening programmes outside randomised clinical trial settings have not been implemented to date owing to lack of robust evidence that such programmes would improve survival and/or quality of life in men with screen-detected disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17826892", "endSection": "abstract" }, { "offsetInBeginSection": 1099, "offsetInEndSection": 1293, "text": "In the case of prostate cancer screening, two systematic reviews have concluded that screening should not be carried out. In general, this recommendation has been accepted in the United Kingdom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11495383", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 244, "text": "Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728749", "endSection": "abstract" }, { "offsetInBeginSection": 1303, "offsetInEndSection": 1450, "text": "the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840664", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 150, "text": "Web-based decision aids are known to have an effect on knowledge, attitude, and behavior; important components of informed decision making", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507844", "endSection": "abstract" }, { "offsetInBeginSection": 1686, "offsetInEndSection": 1818, "text": "Increased usage of Prosdex leads to more informed decision making, the key aim of the UK Prostate Cancer Risk Management Programme. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 697, "text": "Prostate specific antigen (PSA) was introduced as a prostate cancer screening tool more than 20 years ago. However, there is continuing debate regarding its utility in screening for prostate cancer. Mass screening is costly, may result in the diagnosis and treatment of prostate cancers that never become clinically significant, and the evidence of a subsequent reduction in mortality is inconclusive. In addition to its role in screening, PSA is also used to monitor the progression of the disease, both localized and metastatic. Although the evidence is contradictory, PSA is still an important tool for monitoring patient progression following treatment of definitive localized prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20060331", "endSection": "abstract" } ] }, { "body": "Can a peptide aptamer be used as protein inhibitor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20842131", "http://www.ncbi.nlm.nih.gov/pubmed/21296653", "http://www.ncbi.nlm.nih.gov/pubmed/20191379", "http://www.ncbi.nlm.nih.gov/pubmed/18186614", "http://www.ncbi.nlm.nih.gov/pubmed/22956136", "http://www.ncbi.nlm.nih.gov/pubmed/17917077", "http://www.ncbi.nlm.nih.gov/pubmed/16581027", "http://www.ncbi.nlm.nih.gov/pubmed/18195017", "http://www.ncbi.nlm.nih.gov/pubmed/19150354", "http://www.ncbi.nlm.nih.gov/pubmed/10439043", "http://www.ncbi.nlm.nih.gov/pubmed/19389625", "http://www.ncbi.nlm.nih.gov/pubmed/24130701", "http://www.ncbi.nlm.nih.gov/pubmed/22811618", "http://www.ncbi.nlm.nih.gov/pubmed/22714536", "http://www.ncbi.nlm.nih.gov/pubmed/12123800", "http://www.ncbi.nlm.nih.gov/pubmed/22533554", "http://www.ncbi.nlm.nih.gov/pubmed/16815302", "http://www.ncbi.nlm.nih.gov/pubmed/16139842", "http://www.ncbi.nlm.nih.gov/pubmed/24188027" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8405672", "o": "D052158" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "http://linkedlifedata.com/resource/umls/label/A17888724" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "http://linkedlifedata.com/resource/umls/label/A17937093" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17888724", "o": "Aptamers, Peptide [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8405672", "o": "Aptamers, Peptide" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "http://linkedlifedata.com/resource/umls/label/A8405672" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18057015", "o": "Peptide Aptamers" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "http://linkedlifedata.com/resource/umls/label/A18057015" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "http://linkedlifedata.com/resource/umls/label/A8419254" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8419254", "o": "D052158" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8405672", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8419254", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17888724", "o": "N0000170367" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17937093", "o": "N0000170367" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18057015", "o": "N0000170367" } ], "ideal_answer": [ "Yes, peptide aptamers can be used as inhibitors." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/INH_BPT4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010455", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011500", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052158" ], "type": "yesno", "id": "53443b13aeec6fbd0700000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Peptide aptamers of LIM-only protein 2 (Lmo2) were previously used to successfully treat Lmo2-induced tumours in a mouse model of leukaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24188027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Inhibition of mammalian cell proliferation by genetically selected peptide aptamers that functionally antagonize E2F activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10439043", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Accumulating work over the past decade has shown that peptide aptamer screening represents a valid strategy for inhibitor identification that can be applied to a variety of different targets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956136", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 460, "text": ". The target of one inhibitor peptide, Pep80, identified in this screen was determined to be Snapin, a protein associated with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE) complex that is critical for calcium-dependent exocytosis during neurotransmission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24130701", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1174, "text": "Use of the genetically selected intracellular aptamer inhibitors allowed us to define unique mechanisms important to HIV-1 replication and T cell biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24130701", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1688, "text": "This review will describe pre-clinical and clinical data of four major classes of TGF-\u03b2 inhibitor, namely i) ligand traps, ii) antisense oligonucleotides, iii) receptor kinase inhibitors and iv) peptide aptamers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22811618", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 471, "text": " A peptide aptamer (ID1/3-PA7) has been designed to prevent this interaction and thereby leading to the transcription of p16(INK4a).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22714536", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 530, "text": "A peptide kinase inhibitor (IP(20)) was used as the aptameric peptide ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22533554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Peptide aptamer mimicking RAD51-binding domain of BRCA2 inhibits DNA damage repair and survival in Trypanosoma brucei.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21296653", "endSection": "title" }, { "offsetInBeginSection": 593, "offsetInEndSection": 644, "text": " peptide aptamer, Id1/3-PA7, targeting Id1 and Id3,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20842131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Targeting Id1 and Id3 by a specific peptide aptamer induces E-box promoter activity, cell cycle arrest, and apoptosis in breast cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20191379", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Aptamer-derived peptides as potent inhibitors of the oncogenic RhoGEF Tgat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19389625", "endSection": "title" }, { "offsetInBeginSection": 826, "offsetInEndSection": 961, "text": "Our approach thus demonstrates that peptide aptamers are potent inhibitors that can be used to interfere with RhoGEF functions in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19389625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Development of systemic in vitro evolution and its application to generation of peptide-aptamer-based inhibitors of cathepsin E.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19150354", "endSection": "title" }, { "offsetInBeginSection": 525, "offsetInEndSection": 674, "text": "he fusion peptide, TA aptamer, was observed within PC12 cytoplasm and maintained both Abeta-binding ability and antioxygenic property similar to TRX.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17917077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Stable expression of a novel fusion peptide of thioredoxin-1 and ABAD-inhibiting peptide protects PC12 cells from intracellular amyloid-beta.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17917077", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "In order to efficiently select aptamers that bind to and inhibit proteins,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16815302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Aptamer selection based on inhibitory activity using an evolution-mimicking algorithm.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16815302", "endSection": "title" }, { "offsetInBeginSection": 640, "offsetInEndSection": 744, "text": "This demonstrates the utility of this strategy for screening aptamers based on their inhibitory actions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16815302", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 523, "text": "Intracellular expression of the DRD-binding peptide aptamer specifically suppressed receptor-mediated extrinsic apoptosis but not intrinsic pathway, which was recapitulated by the antisense oligonucleotides for FLASH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16581027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Peptide aptamers are peptides constrained and presented by a scaffold protein that are used to study protein function in cells. They are able to disrupt protein-protein interactions ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16139842", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 676, "text": "Here we have used a genetic screen in yeast to select in vivo peptides coupled to thioredoxin, called aptamers, that could inhibit GEFD2 activity. One aptamer, TRIAPalpha (TRio Inhibitory APtamer), specifically blocks GEFD2-exchange activity on RhoA in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12123800", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1375, "text": "These results show that cell proliferation can be inhibited using genetically-selected synthetic peptides that specifically target protein-protein interaction motifs within cell cycle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10439043", "endSection": "abstract" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1776, "text": "These data highlight the utility of peptide aptamers to identify novel binding interfaces and highlight a role for MAP1B in DAPK-1-dependent signaling in autophagy and membrane blebbing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18195017", "endSection": "abstract" } ] }, { "body": "List inflammatory caspase proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21051981", "http://www.ncbi.nlm.nih.gov/pubmed/20401526", "http://www.ncbi.nlm.nih.gov/pubmed/20401456", "http://www.ncbi.nlm.nih.gov/pubmed/22195746", "http://www.ncbi.nlm.nih.gov/pubmed/25943872", "http://www.ncbi.nlm.nih.gov/pubmed/19927353", "http://www.ncbi.nlm.nih.gov/pubmed/20541850", "http://www.ncbi.nlm.nih.gov/pubmed/22895188", "http://www.ncbi.nlm.nih.gov/pubmed/20514521", "http://www.ncbi.nlm.nih.gov/pubmed/23215645", "http://www.ncbi.nlm.nih.gov/pubmed/24280500", "http://www.ncbi.nlm.nih.gov/pubmed/21880711" ], "ideal_answer": [ "caspase-1\ncaspase-4\ncaspase-5" ], "exact_answer": [ [ "caspase-1" ], [ "caspase-4" ], [ "caspase-5" ] ], "type": "list", "id": "571cd9537de986d80d00000e", "snippets": [ { "offsetInBeginSection": 1291, "offsetInEndSection": 1524, "text": " In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25943872", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 607, "text": "However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25943872", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 342, "text": "Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25943872", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 559, "text": "In contrast, engagement of various PRR in the recently identified inflammasome complexes lead to activation of a cysteine protease, caspase-1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24280500", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 331, "text": "ctivation of inflammatory caspase proteases. One such caspase, CASPASE-1 (CASP1), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23215645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Inflammasomes are cytosolic multiprotein complexes assembled by intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and they initiate innate immune responses to invading pathogens and danger signals by activating caspase-1 (ref. 1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22895188", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 611, "text": "e activation of inflammasome by different stimuli triggers the proteolytic cleavage of pro-caspase 1 into active caspase 1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20541850", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 377, "text": "Formation of the inflammasome can lead to the activation of inflammatory caspases, such as Caspase-1, which then activate pro-inflammatory cytokines by proteolytic cleavage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880711", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 503, "text": "inflammatory caspase-1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22195746", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 675, "text": "Human caspase-5 is classified as an inflammatory caspase, although its substrate has not been identified yet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21051981", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 712, "text": "e inflammatory Caspase-1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20401526", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 855, "text": "the inflammatory caspase-1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20401456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Although it is conventionally regarded as an inflammatory caspase, recent studies have shown that caspase-4 plays a role in induction of apoptosis by endoplasmic reticulum (ER) stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20514521", "endSection": "abstract" } ] }, { "body": "List invertebrates where ultraconserved elements have been identified.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16024819", "http://www.ncbi.nlm.nih.gov/pubmed/23217155", "http://www.ncbi.nlm.nih.gov/pubmed/16697139", "http://www.ncbi.nlm.nih.gov/pubmed/15899965", "http://www.ncbi.nlm.nih.gov/pubmed/18514361", "http://www.ncbi.nlm.nih.gov/pubmed/17114937", "http://www.ncbi.nlm.nih.gov/pubmed/23393190" ], "ideal_answer": [ "Ultraconserved elements have been identified in the following genomes of invertebrates: tunicates, diptera, worm and yeast." ], "exact_answer": [ [ "tunicates" ], [ "diptera" ], [ "worm" ], [ "yeast" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007448" ], "type": "list", "id": "553c994af32186855800000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393190", "endSection": "title" }, { "offsetInBeginSection": 231, "offsetInEndSection": 572, "text": "To trace the history of non-coding elements, which may represent candidate ancestral cis-regulatory modules affirmed during chordate evolution, we have searched for conserved elements in tunicate and vertebrate (Olfactores) genomes. We identified, for the first time, 183 non-coding sequences that are highly conserved between the two groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "In a recent study that identified highly evolutionary conserved sequences in three genomes of Diptera species we described an ultraconserved element found at an internal exon-intron junction of the Drosophila melanogaster homothorax (hth) gene that appeared to be involved in the control of hth pre-mRNA splicing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17114937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "We have explored the distributions of fully conserved ungapped blocks in genome-wide pair-wise alignments of recently completed species of Drosophila: D. melanogaster, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis, and D. mojavensis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16697139", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 547, "text": "Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16024819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Ultraconserved elements in insect genomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15899965", "endSection": "title" }, { "offsetInBeginSection": 191, "offsetInEndSection": 400, "text": "Here, we used similar methods to identify ultraconserved genomic regions between the insect species Drosophila melanogaster and Drosophila pseudoobscura, as well as the more distantly related Anopheles gambiae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15899965", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 565, "text": "Here, we identified a wide range of ultraconserved elements common to distant species, from primitive aquatic organisms to terrestrial species with complicated body systems, including some novel elements conserved in fruit fly and human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23217155", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 590, "text": "RESULTS: Here, we identified a wide range of ultraconserved elements common to distant species, from primitive aquatic organisms to terrestrial species with complicated body systems, including some novel elements conserved in fruit fly and human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23217155", "endSection": "abstract" } ] }, { "body": "Which gene is most commonly associated with severe congenital and cyclic neutropenia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20582973", "http://www.ncbi.nlm.nih.gov/pubmed/19057199", "http://www.ncbi.nlm.nih.gov/pubmed/12483111", "http://www.ncbi.nlm.nih.gov/pubmed/17761833", "http://www.ncbi.nlm.nih.gov/pubmed/23463630", "http://www.ncbi.nlm.nih.gov/pubmed/19415009", "http://www.ncbi.nlm.nih.gov/pubmed/11001877", "http://www.ncbi.nlm.nih.gov/pubmed/17053055", "http://www.ncbi.nlm.nih.gov/pubmed/17107353", "http://www.ncbi.nlm.nih.gov/pubmed/11543999", "http://www.ncbi.nlm.nih.gov/pubmed/14962902" ], "ideal_answer": [ "Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (SCN) and cyclic neutropenia (CN).", "Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other " ], "exact_answer": [ "The neutrophil elastase gene (ELANE)" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050590" ], "type": "factoid", "id": "5503133ae9bde6963400001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463630", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 430, "text": "We screened CN (n\u00a0=\u00a0395) or CyN (n\u00a0=\u00a092) patients for ELANE mutations and investigated the impact of mutations on mRNA expression, protein expression, and activity. We found 116 different mutations in 162 (41%) CN patients and 26 in 51 (55%) CyN patients, 69 of them were novel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582973", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 356, "text": "Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582973", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 624, "text": "One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582973", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 202, "text": "Three familial cases of each of severe congenital neutropenia (SCN) and cyclic neutropenia (CN) in addition to 3 sporadic cases of SCN were analyzed for neutrophil elastase (Ela2) gene mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19415009", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 836, "text": "Three cases of familial SCN (P13L, R52P, and S97L), 2 of familial CN (W212stop and P110L), and 1 of sporadic SCN (V72M) were shown to have heterozygous mutations in the Ela2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19415009", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 689, "text": "Recent studies have elucidated a role for the unfolded protein response in mediating the pathogenic effects of ELA2 mutations, the most common mutation in severe congenital neutropenia (SCN) as well as cyclic neutropenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19057199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Mutations of the ELA2 gene encoding neutrophil elastase (NE) are responsible for most cases of SCN and cyclic neutropenia (CN), a related but milder disorder of granulopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17761833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14962902", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 508, "text": "The observation that mutations in the neutrophil elastase gene, which cause cyclic and severe congenital neutropenia, are associated with protease maldistribution gives some clue as to the potential importance of inhibitor proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17107353", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 510, "text": "All cases of cyclic neutropenia and most cases of severe congenital neutropenia result from heterozygous germline mutations in the gene encoding neutrophil elastase, ela2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12483111", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 571, "text": "Mutations in the neutrophil elastase gene were identified in all patients with cyclic neutropenia and most of the patients with severe congenital neutropenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11543999", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 569, "text": "Mutations in the neutrophil elastase gene were identified in all patients with cyclic neutropenia and most of the patients with severe congenital neutropenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11543999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463630", "endSection": "abstract" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1826, "text": "This study indicates that mutations of the gene encoding neutrophil elastase are probably the most common cause for severe congenital neutropenia as well as the cause for sporadic and autosomal dominant cyclic neutropenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11001877", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Mutations in ELA2 encoding the neutrophil granule protease, neutrophil elastase (NE), are the major cause of the 2 main forms of hereditary neutropenia, cyclic neutropenia and severe congenital neutropenia (SCN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17053055", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 251, "text": "Mutations of the ELA2 gene encoding neutrophil elastase (NE) are responsible for most cases of SCN and cyclic neutropenia (CN), a related but milder disorder of granulopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17761833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14962902", "endSection": "abstract" } ] }, { "body": "what is the role of TGFbeta in cardiac regeneration after myocardial injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21611174", "http://www.ncbi.nlm.nih.gov/pubmed/23293297", "http://www.ncbi.nlm.nih.gov/pubmed/22982064", "http://www.ncbi.nlm.nih.gov/pubmed/22765842", "http://www.ncbi.nlm.nih.gov/pubmed/23166366", "http://www.ncbi.nlm.nih.gov/pubmed/23270300", "http://www.ncbi.nlm.nih.gov/pubmed/18620057", "http://www.ncbi.nlm.nih.gov/pubmed/18832581" ], "ideal_answer": [ "TGF\u03b2 is activated in the myocardium in response to injury and plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. In fact, upregulation of TGF-beta signaling promotes the formation of a myofibroblast-like phenotype. TGF-beta interacts with bone morphogenic protein and Wnt pathways to form a complex signaling network that is critical in regulating the fate choices of both stromal and tissue-specific resident stem cells, determining whether functional regeneration or the formation of scar tissue follows an injury. In addition, TGF-beta enhances the formation of cardiospheres and could potentially enhance the regenerative potential of adult cardiac progenitor cells." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016212", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006335", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ], "type": "summary", "id": "530b7ae4970c65fa6b00000b", "snippets": [ { "offsetInBeginSection": 1181, "offsetInEndSection": 1374, "text": "Transforming growth factor (TGF)-beta plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18620057", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 1330, "text": "We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor \u03b2 signaling pathways. Direct examination of heart regeneration after mechanical or genetic ablation injuries indicated that these pathways are activated in regenerating cardiomyocytes and that they can be pharmacologically manipulated to inhibit or enhance cardiomyocyte proliferation during adult heart regeneration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23293297", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1244, "text": "Transforming growth factor beta, bone morphogenic protein and Wnt pathways interact to form a complex signaling network that is critical in regulating the fate choices of both stromal and tissue-specific resident stem cells (TSCs), determining whether functional regeneration or the formation of scar tissue follows an injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23270300", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1089, "text": "In the adult heart under pressure overload, Notch inhibited the development of cardiomyocyte hypertrophy and transforming growth factor-\u03b2/connective tissue growth factor-mediated cardiac fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166366", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1346, "text": "EMT and CSps formation is enhanced in the presence of transforming growth factor \u03b21 (TGF\u03b21) and drastically blocked by the type I TGF\u03b2-receptor inhibitor SB431452, indicating that TGF\u03b2-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGF\u03b2 is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22765842", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 908, "text": "During the proliferative phase of healing, infarct fibroblasts undergo myofibroblast transdifferentiation forming stress fibers and expressing contractile proteins (such as \u03b1-smooth muscle actin). Mechanical stress, transforming growth factor (TGF)-\u03b2/Smad3 signaling and alterations in the composition of the extracellular matrix induce acquisition of the myofibroblast phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982064", "endSection": "abstract" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1765, "text": "Collectively, this data strongly suggests Wnt3a promotes the formation of a myofibroblast-like phenotype in cultured fibroblasts, in part, by upregulating TGF-\u03b2 signaling through SMAD2 in a \u03b2-catenin-dependent mechanism. As myofibroblasts are critical regulators of wound healing responses, these findings may have important implications for our understanding of normal and aberrant injury and repair events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21611174", "endSection": "abstract" }, { "offsetInBeginSection": 1510, "offsetInEndSection": 1733, "text": "Conversely, exogenous addition of TGF-beta to the wound increased VIC activation, proliferation, wound closure rate, and stress fibers. Thus, wounding activates VICs, and TGF-beta signaling modulates VIC response to injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18832581", "endSection": "abstract" } ] }, { "body": "List two chemotherapeutic agents that are used for treatment of Subependymal Giant Cell Astrocytoma", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24667713", "http://www.ncbi.nlm.nih.gov/pubmed/23567018", "http://www.ncbi.nlm.nih.gov/pubmed/24276039", "http://www.ncbi.nlm.nih.gov/pubmed/23686401", "http://www.ncbi.nlm.nih.gov/pubmed/24293099", "http://www.ncbi.nlm.nih.gov/pubmed/24143074", "http://www.ncbi.nlm.nih.gov/pubmed/21047224", "http://www.ncbi.nlm.nih.gov/pubmed/23325902", "http://www.ncbi.nlm.nih.gov/pubmed/22000822", "http://www.ncbi.nlm.nih.gov/pubmed/24729041", "http://www.ncbi.nlm.nih.gov/pubmed/22805244", "http://www.ncbi.nlm.nih.gov/pubmed/22136276", "http://www.ncbi.nlm.nih.gov/pubmed/23231513", "http://www.ncbi.nlm.nih.gov/pubmed/18952591", "http://www.ncbi.nlm.nih.gov/pubmed/24756805", "http://www.ncbi.nlm.nih.gov/pubmed/23158522", "http://www.ncbi.nlm.nih.gov/pubmed/21806479", "http://www.ncbi.nlm.nih.gov/pubmed/24518170", "http://www.ncbi.nlm.nih.gov/pubmed/22262746", "http://www.ncbi.nlm.nih.gov/pubmed/23689226" ], "ideal_answer": [ "Everolimus and rapamycin are chemotherapeutic agents that are used for treatment of Subependymal Giant Cell Astrocytoma." ], "exact_answer": [ [ "everolimus" ], [ "rapamycin" ] ], "type": "list", "id": "54e061ee1388e8454a00000c", "snippets": [ { "offsetInBeginSection": 273, "offsetInEndSection": 612, "text": "Everolimus has been approved by the FDA and the EMA for the treatment of advanced renal cell carcinoma (RCC), subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TSC), pancreatic neuroendocrine tumors (PNET), in combination with exemestane in advanced hormone-receptor (HR)-positive, HER2-negative breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24756805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24729041", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 751, "text": "Our objective was to evaluate everolimus, an mTOR inhibitor, in the treatment of angiomyolipoma in patients with subependymal giant cell astrocytoma (SEGA) associated with TSC. METHODS: EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 (NCT00789828), a prospective, double-blind, randomized, placebo-controlled, Phase 3 study, examined everolimus in treating SEGA associated with TSC. Patients with serial SEGA growth from pre-baseline to baseline scans were randomly assigned (2:1) to receive 4.5 mg/m(2)/day everolimus (target blood trough: 5-15 ng/mL; n = 78) or placebo (n = 39). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24729041", "endSection": "abstract" }, { "offsetInBeginSection": 1693, "offsetInEndSection": 1816, "text": "CONCLUSIONS: Everolimus showed efficacy in reducing angiomyolipoma lesion volume in patients with SEGA associated with TSC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24729041", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 798, "text": "Everolimus has demonstrated substantial clinical benefit in randomized, controlled, phase III studies leading to approval for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, renal angiomyolipoma and subependymal giant-cell astrocytoma associated with tuberous sclerosis complex, as well as advanced hormone-receptor-positive (HR(+)) and human epidermal growth factor receptor-2-negative advanced breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Everolimus for the treatment of subependymal giant cell astrocytoma probably causing seizure aggravation in a child with tuberous sclerosis complex: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293099", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "We are reporting on a 13.5-year-old girl with tuberous sclerosis complex (TSC) who was treated with everolimus because of giant cell astrocytoma and bilateral angiomyolipoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Response of subependymal giant cell astrocytoma with spinal cord metastasis to everolimus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276039", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND: Brain subependymal giant cell astrocytomas (SEGAs) in patients with tuberous sclerosis have been reported to respond to everolimus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276039", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 881, "text": "CONCLUSIONS: We describe a rare case of metastatic SEGA, which was successfully treated with everolimus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276039", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 749, "text": "Additional oncology indications for everolimus include renal angiomyolipoma with tuberous sclerosis complex and subependymal giant-cell astrocytoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23689226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced renal cell carcinoma, pancreatic neuroendocrine tumors, subependymal giant cell astrocytoma associated with tuberous sclerosis complex, renal angiomyolipoma and tuberous sclerosis complex, and, in combination with exemestane, for hormone receptor-positive HER2-negative advanced breast cancer after failure of treatment with letrozole or anastrozole. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Long-term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567018", "endSection": "title" }, { "offsetInBeginSection": 565, "offsetInEndSection": 742, "text": "AIMS: To show the long-term safety data and the effect of everolimus treatment on epilepsy in children under the age of 3 who received everolimus for SEGAs associated with TSC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567018", "endSection": "abstract" }, { "offsetInBeginSection": 1394, "offsetInEndSection": 1577, "text": "CONCLUSIONS: This study suggests that everolimus is effective and safe in infants and young children with epilepsy and SEGA associated with TSC and offers a valuable treatment option.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23325902", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "OBJECTIVE: To report long-term efficacy and safety data for everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23325902", "endSection": "abstract" }, { "offsetInBeginSection": 1291, "offsetInEndSection": 1665, "text": "CONCLUSION: Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that everolimus, titrated to trough serum levels of 5-15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23325902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Everolimus (RAD001): first systemic treatment for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23231513", "endSection": "title" }, { "offsetInBeginSection": 172, "offsetInEndSection": 580, "text": "In patients with subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis complex who are not candidates for surgery, single-agent everolimus has demonstrated the ability to significantly reduce SEGA volume with good tolerability. In the Phase III, randomized, placebo-controlled trial, everolimus was associated with a SEGA response rate of 35% compared with 0% in the placebo group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23231513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23158522", "endSection": "title" }, { "offsetInBeginSection": 320, "offsetInEndSection": 625, "text": "In an open-label, phase 1/2 study, the mTOR inhibitor everolimus substantially and significantly reduced the volume of subependymal giant cell astrocytomas. We assessed the efficacy and safety of everolimus in patients with subependymal giant cell astrocytomas associated with tuberous sclerosis complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23158522", "endSection": "abstract" }, { "offsetInBeginSection": 2272, "offsetInEndSection": 2408, "text": "INTERPRETATION: These results support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23158522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Everolimus for tumor recurrence after surgical resection for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22805244", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "A recent phase 1/2 study demonstrated that treatment with the mammalian target of rapamycin inhibitor everolimus reduced subependymal giant cell astrocytoma volume by 30% in 75% of the patients, all of whom were poor candidates for surgical resection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22805244", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 592, "text": "All 4 experienced over 50% initial reduction in the volume of their subependymal giant cell astrocytoma after 2 to 3 years of therapy with everolimus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22805244", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 437, "text": "METHODS: Recently, a phase I/II trial of everolimus demonstrated significant reductions in subependymal giant cell astrocytoma (SEGA) volume and decreased seizure frequency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22262746", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 632, "text": "TSC patients with SEGA received everolimus, titrated to tolerability to achieve target trough concentrations of 5-15 ng/mL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22262746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Everolimus: in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136276", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR). Everolimus (starting dosage 3.0\u2009mg/m(2)) was associated with a significant reduction in the volume of the largest subependymal giant cell astrocytoma (SEGA) in 28 patients aged \u22653 years with tuberous sclerosis complex (TSC) in a phase II trial (C2485). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136276", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 785, "text": "During the extension phase of this trial (median duration 34 months), the reduction in SEGA volume was maintained, with no everolimus recipient requiring surgery or other therapy for SEGA or hydrocephalus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Effective everolimus treatment of inoperable, life-threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with tuberous sclerosis complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22000822", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22000822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Everolimus tablets for patients with subependymal giant cell astrocytoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21806479", "endSection": "title" }, { "offsetInBeginSection": 382, "offsetInEndSection": 483, "text": "Recently, mTOR inhibitors such as everolimus have shown encouraging benefit for patients with SEGAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21806479", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 1001, "text": "The authors also examine the rationale for targeted agents against this pathway therapeutically and describe the clinical evidence underlying the FDA approval of everolimus for patients with inoperable SEGAs. EXPERT OPINION: Everolimus (Afinitor) selectively targets a molecular defect of SEGAs in TSC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21806479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047224", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 327, "text": "An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047224", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 1087, "text": "Everolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P<0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047224", "endSection": "abstract" }, { "offsetInBeginSection": 2030, "offsetInEndSection": 2288, "text": "CONCLUSIONS: Everolimus therapy was associated with marked reduction in the volume of subependymal giant-cell astrocytomas and seizure frequency and may be a potential alternative to neurosurgical resection in some cases, though long-term studies are needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The authors present a 21-year-old woman who has been receiving rapamycin for 5 months for bilateral subependymal giant cell astrocytomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18952591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22000822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "A recent phase 1/2 study demonstrated that treatment with the mammalian target of rapamycin inhibitor everolimus reduced subependymal giant cell astrocytoma volume by 30% in 75% of the patients, all of whom were poor candidates for surgical resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22805244", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1310, "text": "This review provides an overview of TSC, everolimus, and the clinical trials that led to its approval for the treatment of TSC-associated subependymal giant cell astrocytoma and renal angiomyolipoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24143074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24143074", "endSection": "title" }, { "offsetInBeginSection": 172, "offsetInEndSection": 424, "text": "In patients with subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis complex who are not candidates for surgery, single-agent everolimus has demonstrated the ability to significantly reduce SEGA volume with good tolerability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23231513", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 870, "text": "The authors also examine the rationale for targeted agents against this pathway therapeutically and describe the clinical evidence underlying the FDA approval of everolimus for patients with inoperable SEGAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21806479", "endSection": "abstract" } ] }, { "body": "Are integrins part of the extracellular matrix?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25220424", "http://www.ncbi.nlm.nih.gov/pubmed/26029690", "http://www.ncbi.nlm.nih.gov/pubmed/26096733", "http://www.ncbi.nlm.nih.gov/pubmed/25631868", "http://www.ncbi.nlm.nih.gov/pubmed/24965068", "http://www.ncbi.nlm.nih.gov/pubmed/26067407", "http://www.ncbi.nlm.nih.gov/pubmed/25605337", "http://www.ncbi.nlm.nih.gov/pubmed/25886986", "http://www.ncbi.nlm.nih.gov/pubmed/25759527", "http://www.ncbi.nlm.nih.gov/pubmed/25460334", "http://www.ncbi.nlm.nih.gov/pubmed/26089687" ], "ideal_answer": [ "Yes, \tintegrins are a central family of extracellular matrix receptors." ], "exact_answer": "yes", "type": "yesno", "id": "56e83a2342442bac75000001", "snippets": [ { "offsetInBeginSection": 314, "offsetInEndSection": 451, "text": "Several constituents of the ECM provide adhesive cues, which serve as binding sites for cell trans-membrane receptors, such as integrins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029690", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1129, "text": "We also determined that blocking \u03b21integrins, the major class of receptors for all ECM proteins tested,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26067407", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 298, "text": "Here, we elucidate a cross-scale mechanism for tissue assembly and ECM remodeling involving Cadherin 2, the ECM protein Fibronectin, and its receptor Integrin \u03b15. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26096733", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 604, "text": "due to the diverse functions and variable expression of proteoglycans, matrix proteins, and integrins, it is rather difficult to identify a comprehensive therapeutic target among ECM components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26089687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25605337", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins \u03b1v\u03b23 and \u03b1v\u03b25. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Integrin receptors connect the extracellular matrix to the cell cytoskeleton to provide essential forces and signals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25460334", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 839, "text": " the integrin, talin, and actin filament form a linear complex of which both ends are typically anchored to the extracellular matrices via integrins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24965068", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 338, "text": "Integrins, a central family of cellular ECM receptors, have been implicated in these processes but their specific role in ES cell self-renewal remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25886986", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 446, "text": "Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25631868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25220424", "endSection": "title" } ] }, { "body": "Is Calcium homeostasis important in cardiac physiology and pathophysiology?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23595672", "http://www.ncbi.nlm.nih.gov/pubmed/21750914", "http://www.ncbi.nlm.nih.gov/pubmed/22137362", "http://www.ncbi.nlm.nih.gov/pubmed/24657282", "http://www.ncbi.nlm.nih.gov/pubmed/20347784", "http://www.ncbi.nlm.nih.gov/pubmed/22707075", "http://www.ncbi.nlm.nih.gov/pubmed/23554644", "http://www.ncbi.nlm.nih.gov/pubmed/17517353", "http://www.ncbi.nlm.nih.gov/pubmed/7889444", "http://www.ncbi.nlm.nih.gov/pubmed/22733365", "http://www.ncbi.nlm.nih.gov/pubmed/22673935", "http://www.ncbi.nlm.nih.gov/pubmed/19068246", "http://www.ncbi.nlm.nih.gov/pubmed/17353151", "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "http://www.ncbi.nlm.nih.gov/pubmed/19678847", "http://www.ncbi.nlm.nih.gov/pubmed/20457122", "http://www.ncbi.nlm.nih.gov/pubmed/17509680", "http://www.ncbi.nlm.nih.gov/pubmed/18172603", "http://www.ncbi.nlm.nih.gov/pubmed/21614516", "http://www.ncbi.nlm.nih.gov/pubmed/20875630" ], "ideal_answer": [ "Calcium homeostasis is very important in cardiac physiology and pathophysiology. Maintenance of cellular calcium homeostasis is critical to regulating cardiac contraction. Abnormalities in calcium homeostasis underlie cardiac arrhythmia, contractile dysfunction and cardiac remodelling." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003301", "http://www.biosemantics.org/jochem#4277675", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0055074", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042592" ], "type": "yesno", "id": "54c26e29f693c3b16b000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Maintenance of cellular calcium homeostasis is critical to regulating mitochondrial ATP production and cardiac contraction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24657282", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1753, "text": "the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23595672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Pharmacologic modification of cellular calcium handling recently moved into focus as an alternative for prevention and treatment of ventricular tachyarrhythmias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673935", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1472, "text": "diabetic rats displayed abnormal cardiac structure and systolic and diastolic dysfunction, and spermine (CaSR agonist) could prevent or slow its progression. These results indicate that the CaSR expression of myocardium is reduced in the progress of DCM, and its potential mechanism is related to the impaired intracellular calcium homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137362", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 68, "text": "calcium-sensing receptor (CaSR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Na(+)/Ca(2+) exchanger (NCX) plays important roles in cardiac electrical activity and calcium homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750914", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 321, "text": "NCX current (I(NCX)) shows transmural gradient across left ventricle in many species. Previous studies demonstrated that NCX expression was increased and transmural gradient of I(NCX) was disrupted in failing heart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750914", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 298, "text": "calcium homeostasis, the key process underlying excitation-contraction coupling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21614516", "endSection": "abstract" }, { "offsetInBeginSection": 2057, "offsetInEndSection": 2186, "text": "The results indicate the calcium handling properties of hiPSC-derived cardiomyocytes are relatively immature to hESC counterparts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21614516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 495, "text": "Our understanding of the molecular processes which regulate cardiac function has grown immeasurably in recent years. Even with the advent of \u03b2-blockers, angiotensin inhibitors and calcium modulating agents, heart failure (HF) still remains a seriously debilitating and life-threatening condition. Here, we review the molecular changes which occur in the heart in response to increased load and the pathways which control cardiac hypertrophy, calcium homeostasis, and immune activation during HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875630", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 238, "text": "Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23554644", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1540, "text": "CaSRs are associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23554644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 533, "text": "Important insights into the molecular basis of hypertrophic cardiomyopathy and related diseases have been gained by studying families with inherited cardiac hypertrophy. Integrated clinical and genetic investigations have demonstrated that different genetic defects can give rise to the common phenotype of cardiac hypertrophy. Diverse pathways have been identified, implicating perturbations in force generation, force transmission, intracellular calcium homeostasis, myocardial energetics, and cardiac metabolism in causing disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20347784", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 407, "text": "HAX-1 as a regulator of contractility and calcium cycling in the heart. HAX-1 overexpression reduced sarcoplasmic reticulum Ca-ATPase (SERCA2) pump activity in isolated cardiomyocytes and in vivo, leading to depressed myocyte calcium kinetics and mechanics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1104, "text": "Thus, HAX-1 represents a regulatory mechanism in cardiac calcium cycling and its responses to sympathetic stimulation, implicating its importance in calcium homeostasis and cell survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Calcium ions are the most ubiquitous and versatile signaling molecules in eukaryotic cells. Calcium homeostasis and signaling systems are crucial for both the normal growth of the budding yeast Saccharomyces cerevisiae and the intricate working of the mammalian heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19678847", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1233, "text": "this knowledge can be used to help treat relevant human diseases such as pathological cardiac hypertrophy and heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19678847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "With aging, the heart develops myocyte hypertrophy associated with impaired relaxation indices. To define the cellular basis of this adaptation, we examined the physiological changes that arise in calcium handling in the aging heart and contrasted the adaptations that occur following the imposition of a stimulus that alters calcium homeostasis in a young and an old heart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18172603", "endSection": "abstract" }, { "offsetInBeginSection": 1306, "offsetInEndSection": 1489, "text": "alterations in the calcium-handling machinery of the cardiocyte differ in the context of age and as such may predispose the older heart to the development of a hypertrophic phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18172603", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 142, "text": "The cardiac sodium-calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17517353", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1435, "text": "Thus exchanger overexpression in mice leads to abnormal calcium handling and a decompensatory transition to heart failure with stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17517353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "Central to controlling intracellular calcium concentration ([Ca(2+)](i)) are a number of Ca(2+) transporters and channels with the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) being of particular note in the heart. This review concentrates on the regulation of [Ca(2+)](i) in cardiac muscle and the homeostatic mechanisms employed to ensure that the heart can operate under steady-state conditions on a beat by beat basis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17509680", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1480, "text": "the tight regulation of SR Ca(2+) content is also required to prevent the abnormal, spontaneous or diastolic release of Ca(2+) from the SR. Such diastolic events are a major factor contributing to the genesis of cardiac arrhythmias in disease situations and in recently identified familial mutations in the SR Ca(2+) release channel (ryanodine receptor, RyR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17509680", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 570, "text": "Calcium channels have a unique functional role, because not only do they participate in this activity, they form the means by which electrical signals are converted to responses within the cell. Calcium channels play an integral role in excitation in the heart and shaping the cardiac action potential. In addition, calcium influx through calcium channels is responsible for initiating contraction. Abnormalities in calcium homeostasis underlie cardiac arrhythmia, contractile dysfunction and cardiac remodelling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17353151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Cardiac calcium (Ca(2+)) handling subsumes the mechanisms maintaining the myocardial Ca(2+) homeostasis that contribute essentially to cardiac performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Calcium is an important mediator in cardiac excitation and disorders in cardiac Ca(2+) homeostasis have great influence on the cardiac action potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22733365", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 778, "text": "We review the physiology of the cardiac calcium homeostasis, including the cardiac excitation contraction coupling and myocyte calcium cycling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19068246", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 777, "text": "We review the physiology of the cardiac calcium homeostasis, including the cardiac excitation contraction coupling and myocyte calcium cycling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19068246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Calcium is an important mediator in cardiac excitation and disorders in cardiac Ca(2+) homeostasis have great influence on the cardiac action potential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22733365", "endSection": "abstract" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1576, "text": "The role of calcium in cardiac and vascular smooth muscle physiology was reviewed, highlighting the major mechanisms responsible for maintaining calcium homeostasis in these cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7889444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Energy metabolism and Ca(2+) handling serve critical roles in cardiac physiology and pathophysiology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20457122", "endSection": "abstract" } ] }, { "body": "List available databases containing information about conserved noncoding elements.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "http://www.ncbi.nlm.nih.gov/pubmed/18045502" ], "ideal_answer": [ "Ancora and TFCONES." ], "exact_answer": [ [ "Ancora" ], [ "TFCONES" ] ], "type": "list", "id": "553d061cf321868558000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 519, "text": " We describe Ancora http://ancora.genereg.net, a web resource that provides data and tools for exploring genomic organization of HCNEs for multiple genomes. Ancora includes a genome browser that shows HCNE locations and features novel HCNE density plots as a powerful tool to discover developmental regulatory genes and distinguish their regulatory elements and domains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "TFCONES: a database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045502", "endSection": "title" }, { "offsetInBeginSection": 508, "offsetInEndSection": 769, "text": " We have created a database named TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS) (http://tfcones.fugu-sg.org) which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045502", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1592, "text": "The conserved noncoding elements identified in TFCONES represent a catalog of highly prioritized putative cis-regulatory elements of TF-encoding genes and are candidates for functional assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "TFCONES: a database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045502", "endSection": "title" }, { "offsetInBeginSection": 480, "offsetInEndSection": 608, "text": "We have created a database named TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS) (http://tfcones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045502", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 745, "text": "We have created a database named TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS) (http://tfcones.fugu-sg.org) which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045502", "endSection": "abstract" } ] }, { "body": "What was the purpose of the FANTOM5 project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24669905", "http://www.ncbi.nlm.nih.gov/pubmed/24670763", "http://www.ncbi.nlm.nih.gov/pubmed/24670764" ], "ideal_answer": [ "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome." ], "exact_answer": [ "To provide comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research." ], "type": "factoid", "id": "569e731cca240fa209000003", "snippets": [ { "offsetInBeginSection": 227, "offsetInEndSection": 372, "text": "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669905", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1212, "text": "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670764", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1439, "text": "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670764", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1246, "text": "The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670763", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 504, "text": "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669905", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1213, "text": "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670764", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 373, "text": "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669905", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1125, "text": "The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670763", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 414, "text": "Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670763", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 532, "text": "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. Here we investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669905", "endSection": "abstract" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1224, "text": "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670764", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 361, "text": "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669905", "endSection": "abstract" } ] }, { "body": "Is the gene DUX4 epigenetically regulated in somatic cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23969240", "http://www.ncbi.nlm.nih.gov/pubmed/22522912", "http://www.ncbi.nlm.nih.gov/pubmed/23196547", "http://www.ncbi.nlm.nih.gov/pubmed/23272181", "http://www.ncbi.nlm.nih.gov/pubmed/24278031", "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "http://www.ncbi.nlm.nih.gov/pubmed/24940479", "http://www.ncbi.nlm.nih.gov/pubmed/21734574", "http://www.ncbi.nlm.nih.gov/pubmed/22871573", "http://www.ncbi.nlm.nih.gov/pubmed/22025602", "http://www.ncbi.nlm.nih.gov/pubmed/21060811", "http://www.ncbi.nlm.nih.gov/pubmed/23143600" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16475868", "o": "C532958" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2607370", "o": "http://linkedlifedata.com/resource/umls/label/A16475868" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16475868", "o": "Dux4 protein, mouse" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16475868", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3832170", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1317909", "o": "http://linkedlifedata.com/resource/umls/label/A3832170" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3832170", "o": "DUX4 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1317909", "o": "http://linkedlifedata.com/resource/umls/label/A3840964" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3840964", "o": "double homeobox, 4 protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3840964", "o": "MeSH" } ], "ideal_answer": [ "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Recent studies provide evidence that DUX4 is expressed in the human germline and then epigenetically silenced in somatic cells.", "Yes, the human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.", "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ", "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063185", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044127", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040029", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040030", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057890", "http://www.uniprot.org/uniprot/DUX4_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045858" ], "type": "yesno", "id": "55152c2946478f2f2c000005", "snippets": [ { "offsetInBeginSection": 590, "offsetInEndSection": 853, "text": "There are several genes on chromosome 4q35 region including DUX4 within D4Z4 repeats. Transcription of these genes is usually repressed by epigenetic modifications of this chromosomal region and also accumulation of transcriptional repressors to the repeat array.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196547", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 399, "text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24278031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 1029, "text": " These mice recapitulate important epigenetic and DUX4 expression attributes seen in patients and controls, respectively, including high DUX4 expression levels in the germline, (incomplete) epigenetic repression in somatic tissue, and FSHD-specific variegated DUX4 expression in sporadic muscle nuclei associated with D4Z4 chromatin relaxation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 681, "text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21734574", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1625, "text": "In contrast to control skeletal muscle and most other somatic tissues, full-length DUX4 transcript and protein is expressed at relatively abundant levels in human testis, most likely in the germ-line cells. Induced pluripotent (iPS) cells also express full-length DUX4 and differentiation of control iPS cells to embryoid bodies suppresses expression of full-length DUX4, whereas expression of full-length DUX4 persists in differentiated FSHD iPS cells. Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21060811", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 398, "text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 682, "text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21734574", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 640, "text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21734574", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 396, "text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 897, "text": "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24940479", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 396, "text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24278031", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 899, "text": "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24940479", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 645, "text": "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21734574", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 397, "text": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "endSection": "abstract" }, { "offsetInBeginSection": 1755, "offsetInEndSection": 2022, "text": "The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23969240", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 594, "text": "This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4) gene. DUX4 expresses a transcription factor that plays a major role in the development of FSHD through the initiation of a large gene dysregulation cascade that causes myogenic differentiation defects, atrophy and reduced response to oxidative stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272181", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 581, "text": "decreased epigenetic repression and variegated expression of DUX4 in skeletal muscle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 915, "text": "(incomplete) epigenetic repression in somatic tissue,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23143600", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 232, "text": "derepression of the DUX4 retrogene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22871573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522912", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1162, "text": "Specifically, abundance of RNA transcripts encoded by the DUX4 locus correlated to differential DNA methylation and H3K36me3 enrichment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025602", "endSection": "abstract" }, { "offsetInBeginSection": 1472, "offsetInEndSection": 1623, "text": "Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21060811", "endSection": "abstract" } ] }, { "body": "What is the function of the mammalian gene Irg1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19014335", "http://www.ncbi.nlm.nih.gov/pubmed/12893884", "http://www.ncbi.nlm.nih.gov/pubmed/21424586", "http://www.ncbi.nlm.nih.gov/pubmed/21865384", "http://www.ncbi.nlm.nih.gov/pubmed/16415166", "http://www.ncbi.nlm.nih.gov/pubmed/23455712", "http://www.ncbi.nlm.nih.gov/pubmed/11356686", "http://www.ncbi.nlm.nih.gov/pubmed/15937114", "http://www.ncbi.nlm.nih.gov/pubmed/14500577", "http://www.ncbi.nlm.nih.gov/pubmed/21947773", "http://www.ncbi.nlm.nih.gov/pubmed/7721348" ], "ideal_answer": [ "Human IRG1 and mouse Irg1 mediates antiviral and antimicrobial immune responses, without its exact role having been elucidated. Irg1 has been suggested to have a role in apoptosis and to play a significant role in embryonic implantation. Irg1 is reported as the mammalian ortholog of methylcitrate dehydratase." ], "concepts": [ "http://www.uniprot.org/uniprot/IRG1_MOUSE" ], "type": "summary", "id": "513832a75274a5fb07000012", "snippets": [ { "offsetInBeginSection": 1205, "offsetInEndSection": 1440, "text": "IRG1 is highly upregulated in murine ANA-1 macrophages by several proinflammatory cytokines and Toll-like receptor (TLR) agonists, as well as in spleen and lung of Listeria monocytogenes or Toxoplasma gondii infected mice, respectively", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19014335", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The proinflammatory cytokine-induced IRG1 protein associates with mitochondria", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19014335", "endSection": "title" }, { "offsetInBeginSection": 44, "offsetInEndSection": 143, "text": "multiple genes induced by Borrelia burgdorferi in macrophages to regulate Lyme disease inflammation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947773", "endSection": "title" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1164, "text": "One of these genes, IRG1, was confirmed by single nucleotide polymorphism analysis to be involved in susceptibility. Its precise mechanism remains to be elucidated, although the analysis of gene expression data suggests it has a role in apoptosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865384", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Murine immune-responsive gene 1 (IRG1) plays significant roles in embryonic implantation and neurodegeneration", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21424586", "endSection": "sections.0" }, { "offsetInBeginSection": 638, "offsetInEndSection": 732, "text": "the IRG1 gene is differentially expressed in human fetal PBMCs and LPS-stimulated adult PBMCs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21424586", "endSection": "sections.0" }, { "offsetInBeginSection": 357, "offsetInEndSection": 538, "text": "we identified the immune-responsive gene 1 (IRG1), which was expressed substantially higher in lipopolysaccharide (LPS)-stimulated than in MAP-infected murine macrophage cell lines.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16415166", "endSection": "sections.0" }, { "offsetInBeginSection": 729, "offsetInEndSection": 895, "text": "The inhibitor also blocked induction by LIF of several LIF-regulated genes in the LE including Irg1, which has been shown previously to be essential for implantation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15937114", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500577", "endSection": "title" }, { "offsetInBeginSection": 1510, "offsetInEndSection": 1678, "text": "our studies identified Irg1 as a novel target of PR in the pregnant uterus and also revealed that it is a critical regulator of the early events leading to implantation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500577", "endSection": "sections.0" }, { "offsetInBeginSection": 370, "offsetInEndSection": 647, "text": " This resulted in the identification of one novel P4-regulated gene that had been previously found in lipopolysaccharide-stimulated macrophages and called immune response gene-1 (Irg1) and which is the mammalian ortholog of the bacterial gene encoding methylcitrate dehydratase", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12893884", "endSection": "sections.0" }, { "offsetInBeginSection": 27, "offsetInEndSection": 103, "text": "the mammalian ortholog of methylcitrate dehydratase (immune response gene 1)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12893884", "endSection": "title" }, { "offsetInBeginSection": 358, "offsetInEndSection": 474, "text": "Here we report the isolation of a complementary DNA representing a novel gene, interferon-regulated gene 1 (IRG1). T", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11356686", "endSection": "sections.0" }, { "offsetInBeginSection": 358, "offsetInEndSection": 637, "text": "Here we report the isolation of a complementary DNA representing a novel gene, interferon-regulated gene 1 (IRG1). This gene exhibits significant homology to interferon (IFN)-alpha/beta-inducible human genes p27 and 6-16, indicating that these genes may belong to the same family", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11356686", "endSection": "sections.0" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1065, "text": "The level of IRG1 mRNA again rose transiently on day 4 immediately preceding implantation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11356686", "endSection": "sections.0" }, { "offsetInBeginSection": 1678, "offsetInEndSection": 1856, "text": "Although the functional roles of IRG1 and p27 remain unclear, we describe for the first time, identification of a gene family regulated by IFNalpha in both rodent and human uteri", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11356686", "endSection": "sections.0" }, { "offsetInBeginSection": 1615, "offsetInEndSection": 1711, "text": "Hence, the induction of IRG1 by LPS is mediated by tyrosine kinase and protein kinase C pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7721348", "endSection": "sections.0" } ] }, { "body": "Have hESC been tested for the treatment of age-related macular degeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22281388", "http://www.ncbi.nlm.nih.gov/pubmed/19521979", "http://www.ncbi.nlm.nih.gov/pubmed/20709808", "http://www.ncbi.nlm.nih.gov/pubmed/22514096", "http://www.ncbi.nlm.nih.gov/pubmed/23601133", "http://www.ncbi.nlm.nih.gov/pubmed/25273541" ], "ideal_answer": [ "Yes, human embryonic stem cell (hESC) therapies are being assessed for age-related macular degeneration (AMD)." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4448", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008268", "http://www.disease-ontology.org/api/metadata/DOID:10871" ], "type": "yesno", "id": "56f553aa09dd18d46b000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Development of human embryonic stem cell therapies for age-related macular degeneration", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23601133", "endSection": "title" }, { "offsetInBeginSection": 270, "offsetInEndSection": 736, "text": "In this review, we describe recent approaches to develop cell-based therapies for the treatment of AMD. Recent research has focused on replacing the retinal pigment epithelium (RPE), a monolayer of cells vital to photoreceptor cell health. We discuss the various methods used to differentiate and purify RPE from human embryonic stem cells (HESC), and describe the surgical approaches being used to transplant these cells in existing and forthcoming clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23601133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and is the most common cause of vision loss among the elderly. Stem-cell-based strategies, using human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs), may provide an abundant donor source for generating RPE cells in cell replacement therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20709808", "endSection": "abstract" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1662, "text": "This study contributes to our understanding of the utility of hESC/hiPSC-derived RPE in AMD therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20709808", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 606, "text": "Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19521979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25273541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25273541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19521979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease. RPE cells derived from hESCs (hESC-RPEs) and iPSCs (iPSC-RPEs) express essential RPE markers and can rescue visual function in animal models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514096", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 537, "text": "Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19521979", "endSection": "abstract" } ] }, { "body": "What disease in Loxapine prominently used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7914051", "http://www.ncbi.nlm.nih.gov/pubmed/22014696" ], "ideal_answer": [ "The best indication of loxapine is paranoid schizophrenia." ], "exact_answer": [ "schizophrenia" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008152", "http://www.biosemantics.org/jochem#4122154", "http://www.biosemantics.org/jochem#4274767", "http://www.biosemantics.org/jochem#4090321" ], "type": "factoid", "id": "52b2e409f828ad283c00000e", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 135, "text": "To describe the frequency and trends in the use of antipsychotics for adults with schizophrenia in Canada from 2005 to 2009.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22014696", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 972, "text": "Antipsychotic recommendations were estimated using CDTI data in which schizophrenia was listed as the indication. RESULTS: First-generation antipsychotic (FGA) recommendations for adults with schizophrenia increased by 38% between 2005 and 2009, from 329 380 to 454 960 recommendations. There were notable increases in recommendations for chlorpromazine, loxapine, zuclopenthixol, and flupentixol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22014696", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1212, "text": "Loxapine has been prescribed in France since 1980. Its pharmacological profile is close to that of clozapine: it has dopamine (D2), histamine (H1), serotonin (5-HT2) and adrenergic (alpha 1)-blocking activities. Its best indication seems to be paranoid schizophrenia, although some data suggest bipolar action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7914051", "endSection": "abstract" } ] }, { "body": "What is the systemic nickel allergy syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22217998", "http://www.ncbi.nlm.nih.gov/pubmed/22652902", "http://www.ncbi.nlm.nih.gov/pubmed/24067467", "http://www.ncbi.nlm.nih.gov/pubmed/24256166", "http://www.ncbi.nlm.nih.gov/pubmed/23405604", "http://www.ncbi.nlm.nih.gov/pubmed/23393800", "http://www.ncbi.nlm.nih.gov/pubmed/23527730", "http://www.ncbi.nlm.nih.gov/pubmed/21409856", "http://www.ncbi.nlm.nih.gov/pubmed/19843408", "http://www.ncbi.nlm.nih.gov/pubmed/20378005", "http://www.ncbi.nlm.nih.gov/pubmed/21658331" ], "ideal_answer": [ "A severe form of this allergy is the Systemic nickel allergy syndrome, clinically characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and systemic symptoms (headache, asthenia, itching, and gastrointestinal disorders related to histopathological alterations of gastrointestinal mucosa, borderline with celiac disease)." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009532", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005512" ], "type": "summary", "id": "5325b0419b2d7acc7e000026", "snippets": [ { "offsetInBeginSection": 170, "offsetInEndSection": 324, "text": "patients with \"systemic nickel allergy syndrome\" (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Systemic (gastrointestinal and skin) reactions to ingestion of nickel rich foods in patients with nickel allergic contact dermatitis characterize Systemic Nickel Allergy Syndrome (SNAS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24067467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Nickel ingested with food can elicit either systemic cutaneous or gastrointestinal symptoms causing a systemic nickel allergy syndrome (SNAS) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527730", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 280, "text": "Sistemic Nickel Allergy Syndrome (SNAS) consisting of urticaria-like troubles, itch, erythema, cutaneous rush, headache, intestinal symptoms, recurrent vesicular palmar dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23405604", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 515, "text": "A severe form of this allergy is the Systemic nickel allergy syndrome, clinically characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and systemic symptoms (headache, asthenia, itching, and gastrointestinal disorders related to histopathological alterations of gastrointestinal mucosa, borderline with celiac disease).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22652902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Some patients with nickel (Ni) allergic contact dermatitis (ACD) suffer from systemic symptoms after ingestion of Ni-rich foods, a condition termed Systemic Nickel Allergy Syndrome (SNAS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22217998", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 776, "text": "Recently a Systemic Nickel Allergy Syndrome (SNAS) has been identified in allergic subjects, with a clinical picture of urticaria, general hitching, headache, gastrointestinal troubles. SNAS may affect allergic occupational or non-occupational ones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Some patients affected by nickel-contact allergy present digestive symptoms in addition to systemic cutaneous manifestations, falling under the condition known as systemic nickel allergy syndrome (SNAS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21658331", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 977, "text": "systemic nickel allergy syndrome (SNAS). The SNAS can have cutaneous signs and symptoms (Systemic Contact Dermatitis or SCD) or extracutaneous signs and symptoms (gastrointestinal, respiratory, neurological, etc.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21409856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic (intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and experience symptoms reduction with low-Ni diet, a condition termed Systemic Ni Allergy Syndrome (SNAS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378005", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 301, "text": "\"systemic nickel allergy syndrome\" (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843408", "endSection": "abstract" } ] }, { "body": "Which antibodies cause Riedel thyroiditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "http://www.ncbi.nlm.nih.gov/pubmed/26273473", "http://www.ncbi.nlm.nih.gov/pubmed/24783026", "http://www.ncbi.nlm.nih.gov/pubmed/22498583", "http://www.ncbi.nlm.nih.gov/pubmed/25224542", "http://www.ncbi.nlm.nih.gov/pubmed/21881964", "http://www.ncbi.nlm.nih.gov/pubmed/22210556" ], "ideal_answer": [ "Riedel thyroiditis (Immunoglobulin G4-related thyroid disease) is caused by IgG4 antibodies. It is part of the spectrum of Ig4-related sclerosing disease.\nIt is associated with fibrosis and inflammation of the thyroid gland." ], "exact_answer": [ "IgG4" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:7188", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013966", "http://www.disease-ontology.org/api/metadata/DOID:7166", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906" ], "type": "factoid", "id": "56c1f040ef6e394741000055", "snippets": [ { "offsetInBeginSection": 934, "offsetInEndSection": 1080, "text": "LEARNING POINTS: There are potential clinical applications of identifying subsets of patients with IgG4 thyroiditis (FVHT and Riedel thyroiditis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26273473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "The importance of IgG4 in the predictive model of thyroiditis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26273473", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Increased lymphangiogenesis in Riedel thyroiditis (Immunoglobulin G4-related thyroid disease).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1378, "text": "Our findings support the inclusion of RT within the spectrum of IgG4-related thyroid disease (IgG4-RTD). Although the etiology and physiopathology of IgG4-RTD still remain elusive, the results obtained in the present case suggest the participation of lymphatic vessels in the pathogenesis of RT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 734, "text": "More than 80 % of the left thyroid lobe was effaced by fibrosis and inflammation (lymphocytes, 57 IgG4+ plasma cells per 1 high-power field, an IgG4/IgG ratio of 0.67, and eosinophils) with extension into the surrounding tissues and occlusive phlebitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 624, "text": "Diagnosed early as Riedel disease, the high serum IgG4, immunohistopathology and decreased fibrosis with corticosteroid therapy, finally confirm for the first time, the origin of IgG4-RSD fibrosis of the thyroid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25224542", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 298, "text": " While IgG4-RSD is well documented in the pancreas and other organs, it is poorly characterized in the thyroid gland. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25224542", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 357, "text": "He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24783026", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 978, "text": "The relationship between HT and Riedel thyroiditis remains unclear; however, recent evidence seems to suggest that it may also be part of the spectrum of Ig4-related sclerosing disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22498583", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1534, "text": " One patient with advanced thyroid fibrosis associated with Riedel thyroiditis and a history of disease in multiple other organ systems did not have improvement in the thyroid gland, but the disease did not progress to involve new organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22210556", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 531, "text": "IgG4RD may be present in a certain proportion of patients with a wide variety of diseases, including Mikulicz's disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21881964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Increased lymphangiogenesis in Riedel thyroiditis (Immunoglobulin G4-related thyroid disease)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "endSection": "abstract" } ] }, { "body": "What are the effects of ILK ablation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19575460", "http://www.ncbi.nlm.nih.gov/pubmed/19920070", "http://www.ncbi.nlm.nih.gov/pubmed/16951252", "http://www.ncbi.nlm.nih.gov/pubmed/20980390", "http://www.ncbi.nlm.nih.gov/pubmed/16837631", "http://www.ncbi.nlm.nih.gov/pubmed/20564195", "http://www.ncbi.nlm.nih.gov/pubmed/22658851", "http://www.ncbi.nlm.nih.gov/pubmed/19349584", "http://www.ncbi.nlm.nih.gov/pubmed/18846549" ], "ideal_answer": [ "Depending on the tissue or cell where ILK is ablated we see different effects:\nAblation of ILK in heart results in dilated cardiomyopathy and spontaneous heart failure\nAblation of ILK in fibroblasts leads to impaired healing due to a severe reduction in the number of myofibroblasts\nAblation of ILK in osteoclasts inhibits bone resorption\nAblation of ILK in liver results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration and in abnormal histology\nAblation of ILK in podocytes caused an aberrant distribution of nephrin and alpha-actinin-4" ], "exact_answer": [ [ "Ablation of ILK in heart results in dilated cardiomyopathy and spontaneous heart failure" ], [ "Ablation of ILK in fibroblasts leads to impaired healing due to a severe reduction in the number of myofibroblasts" ], [ "Ablation of ILK in osteoclasts inhibits bone resorption" ], [ "Ablation of ILK in liver results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration and in abnormal histology" ], [ "Ablation of ILK in podocytes caused an aberrant distribution of nephrin and alpha-actinin-4" ] ], "concepts": [ "http://www.uniprot.org/uniprot/ILK_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055011", "http://www.uniprot.org/uniprot/ILK_HUMAN" ], "type": "list", "id": "5179602c8ed59a060a00003d", "snippets": [ { "offsetInBeginSection": 450, "offsetInEndSection": 544, "text": "ILK knockdown had no effect on the viability or survival pathway activity pattern of MM cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22658851", "endSection": "sections.0" }, { "offsetInBeginSection": 768, "offsetInEndSection": 869, "text": "We conclude that ILK does not play a prominent role in the promotion or sustenance of established MM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22658851", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Defective granulation tissue formation in mice with specific ablation of integrin-linked kinase in fibroblasts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20980390", "endSection": "title" }, { "offsetInBeginSection": 311, "offsetInEndSection": 558, "text": "Here, we show that fibroblast-restricted inactivation of ILK in mice leads to impaired healing due to a severe reduction in the number of myofibroblasts, whereas inflammatory infiltrate and vascularization of the granulation tissue are unaffected.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20980390", "endSection": "sections.0" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1152, "text": "in fibroblasts, ILK is crucial for limiting RhoA activity, thus promoting TGF\u03b21 production, which is essential for dermal repair following injury.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20980390", "endSection": "sections.0" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1530, "text": "Our results show that ILK is important for the function, but not the differentiation, of osteoclasts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20564195", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20564195", "endSection": "title" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1622, "text": "ack of ILK in the hepatocytes imparts prolonged proliferative response not only to stimuli related to liver regeneration but also to xenobiotic chemical mitogens, such as PB.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920070", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Liver-specific ablation of integrin-linked kinase in mice results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920070", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19575460", "endSection": "title" }, { "offsetInBeginSection": 794, "offsetInEndSection": 966, "text": "ILK deficiency caused an aberrant distribution of nephrin and alpha-actinin-4 in podocytes, whereas the localization of podocin and synaptopodin remained relatively intact.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16837631", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951252", "endSection": "title" }, { "offsetInBeginSection": 155, "offsetInEndSection": 309, "text": "Here we show that targeted ablation of the integrin-linked kinase (ILK) expression results in spontaneous cardiomyopathy and heart failure by 6 wk of age.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951252", "endSection": "sections.0" }, { "offsetInBeginSection": 637, "offsetInEndSection": 768, "text": "Together, these results suggest that ILK plays a central role in protecting the mammalian heart against cardiomyopathy and failure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951252", "endSection": "sections.0" }, { "offsetInBeginSection": 1653, "offsetInEndSection": 1810, "text": "Our results show for the first time in vivo the significance of ILK and hepatic ECM-signaling for regulation of hepatocyte proliferation and differentiation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18846549", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18846549", "endSection": "title" } ] }, { "body": "Does d-tubocurarine (d-TC) induces irreversible inhibition of nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9788777", "http://www.ncbi.nlm.nih.gov/pubmed/11562442", "http://www.ncbi.nlm.nih.gov/pubmed/16931985", "http://www.ncbi.nlm.nih.gov/pubmed/9291508", "http://www.ncbi.nlm.nih.gov/pubmed/6141831", "http://www.ncbi.nlm.nih.gov/pubmed/2611499", "http://www.ncbi.nlm.nih.gov/pubmed/11867382", "http://www.ncbi.nlm.nih.gov/pubmed/2002334", "http://www.ncbi.nlm.nih.gov/pubmed/12145052", "http://www.ncbi.nlm.nih.gov/pubmed/21453711", "http://www.ncbi.nlm.nih.gov/pubmed/2066280", "http://www.ncbi.nlm.nih.gov/pubmed/1884116", "http://www.ncbi.nlm.nih.gov/pubmed/3781972" ], "ideal_answer": [ "The d-tubocurarine is a nondepolarizing neuromuscular blocking agent (nondepolarizing muscle relaxant - NDMR). The nondepolarizing muscle relaxants act by blocking the nicotinic acetylcholine receptors of the neuromuscular junction. The neuromuscular blocking action of tubocurarine is reversible and concentration-dependent. The inhibition of acetylcholine-induced currents by d-tubocurarine can be reversed by anticholinesterase agents, such as edrophonium and methamidophos." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0015464", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005892", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011978", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009469", "http://www.biosemantics.org/jochem#4273076", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031594" ], "type": "yesno", "id": "554614bcd355485447000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3781972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The ability of hexamethonium (C6) to reverse the neuromuscular blocking action of tubocurarine (Tc)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6141831", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 353, "text": "Volatile anesthetics enhance the neuromuscular blockade produced by nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a postulated site of this interaction. We tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12145052", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 954, "text": "Concentration-effect curves for the inhibition of acetylcholine-induced currents were established for vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the volatile anesthetics at a concentration equivalent to half the concentration producing a 50% inhibition alone. All individually tested compounds produced rapid and readily reversible concentration-dependent inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12145052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "The pharmacological diversity of the different isoforms of the nicotinic acetylcholine receptor arises from the diversity of the subunits that assemble to form the native receptors. The aim of this study was to investigate the actions of the muscle relaxants d-tubocurarine, pancuronium and vecuronium on different isoforms of nicotinic acetylcholine receptors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9788777", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1029, "text": "At all three receptor types, d-tubocurarine and pancuronium blocked the responses elicited by acetylcholine in a reversible manner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9788777", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 861, "text": "As further evidence of anticholinesterase activity, methamidophos (1-100 microM) was able to reverse the blockade by d-tubocurarine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9291508", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 800, "text": "There was an initial partial reversal of the neuromuscular inhibition caused by tubocurarine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2611499", "endSection": "abstract" }, { "offsetInBeginSection": 1676, "offsetInEndSection": 1814, "text": "Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12145052", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1437, "text": "Because other purinergic 2X (P2X) receptor antagonists, NF023 and NF279, do not have the reverse effects on the neuromuscular blockade of d-TC, the effect of NF449 seems irrelevant to inhibition of P2X receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21453711", "endSection": "abstract" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1464, "text": "The association rate constant for Tc binding to sites on the nicotinic acetylcholine receptor appears to be very fast (k+D = 8.9 x 10(8) M-1 s-1) and comparable to that for acetylcholine (ACh).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1884116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The aim of this study was to investigate the mechanism for the reversal effect of NF449 (a suramin analogue) on the neuromuscular block induced by d-tubocurarine (d-TC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21453711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21453711", "endSection": "title" } ] }, { "body": "Which receptors are bound by Tasimelteon?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25423562", "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "http://www.ncbi.nlm.nih.gov/pubmed/24610704", "http://www.ncbi.nlm.nih.gov/pubmed/25207602", "http://www.ncbi.nlm.nih.gov/pubmed/19579175", "http://www.ncbi.nlm.nih.gov/pubmed/24228714", "http://www.ncbi.nlm.nih.gov/pubmed/25422900", "http://www.ncbi.nlm.nih.gov/pubmed/20945020" ], "ideal_answer": [ "Tasimelteon (HETLIOZ\u2122) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder." ], "exact_answer": [ [ "MT1" ], [ "MT2" ] ], "type": "list", "id": "56c1f043ef6e394741000057", "snippets": [ { "offsetInBeginSection": 124, "offsetInEndSection": 648, "text": "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 751, "text": "The drugs covered target GABAA (zaleplon-CR, lorediplon, EVT-201), orexin (filorexant, MIN-202), histamine-H1 (LY2624803), serotonin 5-HT2A (ITI-007), melatonin/serotonin5-HT1A (piromelatine) and melatonin (indication expansions of prolonged-release melatonin and tasimelteon for pediatric sleep and circadian rhythm disorders) receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25423562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythms sleep-wake disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25207602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Tasimelteon (HETLIOZ\u2122) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24610704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Numerous physiological functions of the pineal gland hormone melatonin are mediated via activation of two G-protein-coupled receptors, MT1 and MT2. The melatonergic drugs on the market, ramelteon and agomelatine, as well as the most advanced drug candidates under clinical evaluation, tasimelteon and TIK-301, are high-affinity nonselective MT1/MT2 agonists. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24228714", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 326, "text": "A new melatonin 1 and melatonin 2 agonist tasimelteon improves sleep in these patients, resetting their circadian sleep-wake clocks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25422900", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1484, "text": "A general suitability in mitigating other symptoms of major depressive disorder cannot be deduced from the actions of tasimelteon via the melatonin receptors MT1 and MT2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19579175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Tasimelteon (HETLIOZ\u2122) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24610704", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 571, "text": "Ramelteon and tasimelteon are new chrono-hypnotic agents, selective for melatonin MT1 and MT2 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20945020", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 649, "text": "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1321, "text": "A general suitability in mitigating other symptoms of major depressive disorder cannot be deduced from the actions of tasimelteon via the melatonin receptors MT1 and MT2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19579175", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 303, "text": "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 648, "text": "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 649, "text": "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 790, "text": "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively). Tasimelteon was also shown to have no appreciable affinity for more than 160 other pharmacologically relevant receptors and several enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": " Hetlioz(\u00ae) (tasimelteon) is the first approved treatment in the United States for Non-24-Hour Sleep-Wake Disorder (Non-24). We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 649, "text": "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 304, "text": "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "endSection": "abstract" } ] }, { "body": "Is zyxin a focal adhesion protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22553491", "http://www.ncbi.nlm.nih.gov/pubmed/23454549", "http://www.ncbi.nlm.nih.gov/pubmed/23336069", "http://www.ncbi.nlm.nih.gov/pubmed/21598955", "http://www.ncbi.nlm.nih.gov/pubmed/23742986", "http://www.ncbi.nlm.nih.gov/pubmed/23267329", "http://www.ncbi.nlm.nih.gov/pubmed/22778267", "http://www.ncbi.nlm.nih.gov/pubmed/21889443", "http://www.ncbi.nlm.nih.gov/pubmed/23254340", "http://www.ncbi.nlm.nih.gov/pubmed/24039980", "http://www.ncbi.nlm.nih.gov/pubmed/20139076", "http://www.ncbi.nlm.nih.gov/pubmed/19853601", "http://www.ncbi.nlm.nih.gov/pubmed/22609203", "http://www.ncbi.nlm.nih.gov/pubmed/24157374", "http://www.ncbi.nlm.nih.gov/pubmed/19856213", "http://www.ncbi.nlm.nih.gov/pubmed/20801875", "http://www.ncbi.nlm.nih.gov/pubmed/22516607", "http://www.ncbi.nlm.nih.gov/pubmed/23028903", "http://www.ncbi.nlm.nih.gov/pubmed/23687301", "http://www.ncbi.nlm.nih.gov/pubmed/19173742" ], "triples": [ { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/A5H447", "o": "http://purl.uniprot.org/keywords/130" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/130", "o": "Cell adhesion" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/A5H447", "o": "http://linkedlifedata.com/resource/#_413548343437008" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413548343437008", "o": "Zyxin" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q04584", "o": "http://purl.uniprot.org/keywords/130" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513034353834008", "o": "Zyxin" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q04584", "o": "http://linkedlifedata.com/resource/#_513034353834008" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q0VA45", "o": "http://purl.uniprot.org/keywords/130" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513056413435009", "o": "Zyxin" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q0VA45", "o": "http://linkedlifedata.com/resource/#_513056413435009" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q62523", "o": "http://purl.uniprot.org/keywords/130" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136323532330010", "o": "Zyxin" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q62523", "o": "http://linkedlifedata.com/resource/#_5136323532330010" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/A5H447", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0005925" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0005925", "o": "focal adhesion" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0005925", "o": "focal contact" }, { "p": "http://www.w3.org/2004/02/skos/core#relatedSynonym", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0005925", "o": "hemi-adherens junction" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q04584", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0005925" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q0VA45", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0005925" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q62523", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0005925" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q15942", "o": "http://purl.uniprot.org/go/0005925" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513135393432002F", "o": "Zyxin" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0005925", "o": "http://www.geneontology.org/go#GO:0005925" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5131353934320030", "o": "Zyxin-2" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-444225", "o": "ZYX" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0005925", "o": "focal adhesion" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0005925", "o": "focal contact" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q15942", "o": "http://linkedlifedata.com/resource/#_5131353934320030" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/intact/EBI-444225", "o": "http://purl.uniprot.org/uniprot/Q15942" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q15942", "o": "http://linkedlifedata.com/resource/#_513135393432002F" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0005925", "o": "hemi-adherens junction" } ], "ideal_answer": [ "Yes, zyxin is a focal adhesion protein." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060589", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051894", "http://www.uniprot.org/uniprot/ZYX_HUMAN", "http://www.uniprot.org/uniprot/ZYX_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005925", "http://www.uniprot.org/uniprot/ZYX_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048041", "http://www.uniprot.org/uniprot/ZYX_XENTR", "http://www.uniprot.org/uniprot/ZYX_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022001", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002448" ], "type": "yesno", "id": "54f4b319d0d681a040000005", "snippets": [ { "offsetInBeginSection": 518, "offsetInEndSection": 533, "text": " zyxin from FAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039980", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1271, "text": "zyxin relocation from focal adhesions ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157374", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 487, "text": ". Here we systematically examined the expression, localization, and function of zyxin, a focal adhesion protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742986", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 607, "text": "focal adhesion protein zyxin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23336069", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1270, "text": "Focal adhesions formed in the absence of \u03b1-actinins are delayed in their maturation, exhibit altered morphology, have decreased amounts of Zyxin and VASP, and reduced adhesiveness to extracellular matrix", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23454549", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 751, "text": "one focal adhesion protein (zyxin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23687301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Zyxin is a focal adhesion protein that has been implicated in the modulation of cell adhesion and motility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23267329", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 677, "text": " focal adhesion proteins (vinculin, talin, zyxin, FAK, and paxilin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23254340", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1340, "text": "Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028903", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 523, "text": "Zyxin concentrates at focal adhesions ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22778267", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 196, "text": "zyxin, a focal adhesion protein,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22609203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Focal adhesion proteins Zyxin and Vinculin are co-distributed at tubulobulbar complexes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553491", "endSection": "title" }, { "offsetInBeginSection": 785, "offsetInEndSection": 918, "text": " Here we explore the prediction that zyxin, a focal adhesion protein known to be present at podosomes, also is present at apical TBCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553491", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 805, "text": "the association of zyxin with focal adhesions is force-dependent, smaller zyxin-positive adhesion as well as its higher turnover rate suggests that the traction force in focal adhesion on 350 nm topography is decreased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516607", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 267, "text": ". Zyxin is a focal adhesion protein that responds to external mechanical forces;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21889443", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 423, "text": "Vinculin and zyxin in focal adhesions but not integrins are seen to bridge ligand gaps. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21598955", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 131, "text": "The focal adhesion protein zyxin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20801875", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 592, "text": ". To explore how this response is regulated by focal adhesion-associated proteins the expression levels of paxillin, focal adhesion kinase (FAK), and zyxin were knocked down using gene silencing techniques", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19856213", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1239, "text": " Zyxin is an adaptor protein at focal adhesion plaque", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19173742", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1020, "text": "ocked localization of zyxin at focal adhesion sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19853601", "endSection": "abstract" } ] }, { "body": "What is the role of ELMO1 gene in cell migration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11595183", "http://www.ncbi.nlm.nih.gov/pubmed/22503503", "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "http://www.ncbi.nlm.nih.gov/pubmed/23591873", "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "http://www.ncbi.nlm.nih.gov/pubmed/20466982", "http://www.ncbi.nlm.nih.gov/pubmed/12029088", "http://www.ncbi.nlm.nih.gov/pubmed/24819662", "http://www.ncbi.nlm.nih.gov/pubmed/16377631", "http://www.ncbi.nlm.nih.gov/pubmed/15952790" ], "ideal_answer": [ "ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex. In mammalian cells, ELMO1 interacts with Dock180 as a component of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration. We also show that Hck and ELMO1 interact in intact cells and that ELMO1 is heavily tyrosine-phosphorylated in cells that co-express Hck, suggesting that it is a substrate of Hck.The ELMO1/DOCK180 complex then forms a guanine nucleotide exchange factor for Rac1, regulating its activation during cell migration in different biological systems. Rac activation by the ELMO.Dock180 complex at discrete intracellular locations is mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.", "Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016477", "http://www.uniprot.org/uniprot/ELMO1_HUMAN" ], "type": "summary", "id": "56c2fbd91e69116444000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24819662", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 220, "text": "Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24819662", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1513, "text": "Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24819662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Elmo1 and Elmo2 are highly homologous cytoplasmic adaptor proteins that interact with Dock family guanine nucleotide exchange factors to promote activation of the small GTPase Rac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1711, "text": "This work provides valuable insights into the molecular regulation of Dock2 by Elmo1 that can be used to design improved inhibitors that target the Elmo-Dock-Rac signaling complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1403, "text": "Taken together, these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 491, "text": "Here we show that CXCL12 stimulation promotes interaction between G\u03b1i2 and ELMO1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591873", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 762, "text": "Gi signalling and ELMO1 are both required for CXCL12-mediated actin polymerization, migration and invasion of breast cancer cells. CXCL12 triggers a G\u03b1i2-dependent membrane translocation of ELMO1, which associates with Dock180 to activate small G-proteins Rac1 and Rac2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591873", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1073, "text": "Our findings indicate that a chemokine-controlled pathway, consisting of G\u03b1i2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591873", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1327, "text": "These findings suggest that clearance of apoptotic cells in living vertebrates is accomplished by the combined actions of apoptotic cell migration and elmo1-dependent macrophage engulfment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503503", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 928, "text": "Mechanistically, we identified Netrin-1 and its receptor Unc5B as upstream activators of the ELMO1/DOCK180 complex, regulating its functional interaction and leading to Rac1 activation in endothelial cells and vessel formation in zebrafish", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20466982", "endSection": "abstract" }, { "offsetInBeginSection": 63, "offsetInEndSection": 222, "text": "The ELMO1/DOCK180 complex forms a guanine nucleotide exchange factor for Rac1, regulating its activation during cell migration in different biological systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20466982", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 376, "text": "ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16377631", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1591, "text": "Finally, in contrast to most other ERM-binding proteins, ELMO1 binding occurred independently of the state of radixin C-terminal phosphorylation, suggesting an ELMO1 interaction with both the active and inactive forms of ERM proteins and implying a possible role of ELMO in localizing or retaining ERM proteins in certain cellular sites. Together these data suggest that ELMO1-mediated cytoskeletal changes may be coordinated with ERM protein crosslinking activity during dynamic cellular functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16377631", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 672, "text": "In mammalian fibroblasts, ELMO1 binds to Dock180, and functions upstream of Rac during phagocytosis and cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15952790", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 771, "text": "We previously showed that ELMO1 binds directly to the Hck SH3 domain and is phosphorylated by Hck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15952790", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1473, "text": "The data suggest that Src family kinase mediated tyrosine phosphorylation of ELMO1 might represent an important regulatory mechanism that controls signaling through the ELMO1/Crk/Dock180 pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15952790", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1045, "text": "We also found that ELMO1 regulated multiple Dock180 superfamily members to promote migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1522, "text": "This finding suggests that Rac activation by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 816, "text": "In mammalian cells, ELMO1 interacts with Dock180 as a component of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12029088", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1325, "text": "The binding of ELMO1 to Hck is specifically dependent on the interaction of a polyproline motif with the SH3 domain of Hck. Our results suggest that these proteins may be novel activators/effectors of Hck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12029088", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1118, "text": "We also show that Hck and ELMO1 interact in intact cells and that ELMO1 is heavily tyrosine-phosphorylated in cells that co-express Hck, suggesting that it is a substrate of Hck", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12029088", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1403, "text": "these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Essential role of Elmo1 in Dock2-dependent lymphocyte migration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "endSection": "title" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1405, "text": "Taken together, these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "endSection": "abstract" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1405, "text": "nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 596, "text": "Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1512, "text": "Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24819662", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 594, "text": "Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 596, "text": "Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1523, "text": "This finding suggests that Rac activation by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 830, "text": "These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11595183", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 673, "text": "elegans, ced-12 is required for the engulfment of dying cells and for cell migration. In mammalian fibroblasts, ELMO1 binds to Dock180, and functions upstream of Rac during phagocytosis and cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15952790", "endSection": "abstract" } ] }, { "body": "What is the biological role of K-48 linked protein ubiquitination?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22389394", "http://www.ncbi.nlm.nih.gov/pubmed/20696248", "http://www.ncbi.nlm.nih.gov/pubmed/19432818", "http://www.ncbi.nlm.nih.gov/pubmed/15728425", "http://www.ncbi.nlm.nih.gov/pubmed/19887490", "http://www.ncbi.nlm.nih.gov/pubmed/24126522" ], "ideal_answer": [ "The proteasome, which identifies and destroys unwanted proteins rapidly, plays a vital role in maintaining cellular protein homeostasis. Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine (K) 48 that targets them to the proteolytic machinery. K(48)-linked polyubiquitinated proteins are degraded by the proteasomes to elevate cellular levels of amino acids needed for intracellular proliferation. NF-\u03baB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-\u03baB precursors and the degradation of inhibitor of kappa B (I\u03baB) proteins." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016567" ], "type": "summary", "id": "5507fc114b2a315d41000003", "snippets": [ { "offsetInBeginSection": 191, "offsetInEndSection": 392, "text": "On the LCV, AnkB triggers docking of K(48)-linked polyubiquitinated proteins that are degraded by the host proteasomes to elevate cellular levels of amino acids needed for intracellular proliferation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24126522", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1560, "text": "Transcription and injection of ankB is triggered by attached extracellular bacteria followed by rapid farnesylation and anchoring of AnkB to the cytosolic side of the plasma membrane beneath bacterial attachment, where K(48)-linked polyubiquitinated proteins are assembled and degraded by the proteasomes, leading to a rapid rise in the cellular levels of amino acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24126522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 478, "text": "Although it has been known for a long time that ubiquitylation has a major role in the activation and regulation of the nuclear factor kappa B (NF-\u03baB) pathway, recent studies have revealed that the picture is a lot more complex than originally thought. NF-\u03baB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-\u03baB precursors and the degradation of inhibitor of kappa B (I\u03baB) proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22389394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "The proteasome, which identifies and destroys unwanted proteins rapidly, plays a vital role in maintaining cellular protein homeostasis. Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine (K) 48 that targets them to the proteolytic machinery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20696248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Covalent and reversible post-translational modifications of proteins are a common theme in signaling. Ubiquitin conjugation was originally described to target proteins to proteasomal degradation by ubiquitin polymerization involving lysine (K) 48 residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Proteins tagged with lysine (Lys, K) 48 polyubiquitins chains are destined for degradation by the 26S proteasomal system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19432818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 541, "text": "Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15728425", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1197, "text": "Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15728425", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 479, "text": "NF-\u03baB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-\u03baB precursors and the degradation of inhibitor of kappa B (I\u03baB) proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22389394", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 476, "text": "NF-\u03baB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-\u03baB precursors and the degradation of inhibitor of kappa B (I\u03baB) proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22389394", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 316, "text": "Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine (K) 48 that targets them to the proteolytic machinery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20696248", "endSection": "abstract" } ] }, { "body": "Could DNA (cytosine-5-)-methyltransferases serve as tumour markers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21993668", "http://www.ncbi.nlm.nih.gov/pubmed/22490330", "http://www.ncbi.nlm.nih.gov/pubmed/19468253", "http://www.ncbi.nlm.nih.gov/pubmed/18639561", "http://www.ncbi.nlm.nih.gov/pubmed/15854288", "http://www.ncbi.nlm.nih.gov/pubmed/21045206", "http://www.ncbi.nlm.nih.gov/pubmed/21458988", "http://www.ncbi.nlm.nih.gov/pubmed/21629434", "http://www.ncbi.nlm.nih.gov/pubmed/20460473", "http://www.ncbi.nlm.nih.gov/pubmed/19723570", "http://www.ncbi.nlm.nih.gov/pubmed/17071074", "http://www.ncbi.nlm.nih.gov/pubmed/14742272", "http://www.ncbi.nlm.nih.gov/pubmed/17046852", "http://www.ncbi.nlm.nih.gov/pubmed/20613874", "http://www.ncbi.nlm.nih.gov/pubmed/23251566", "http://www.ncbi.nlm.nih.gov/pubmed/16053511", "http://www.ncbi.nlm.nih.gov/pubmed/1684097", "http://www.ncbi.nlm.nih.gov/pubmed/15499388", "http://www.ncbi.nlm.nih.gov/pubmed/18097598", "http://www.ncbi.nlm.nih.gov/pubmed/21521786", "http://www.ncbi.nlm.nih.gov/pubmed/21150312", "http://www.ncbi.nlm.nih.gov/pubmed/15509558", "http://www.ncbi.nlm.nih.gov/pubmed/23177624", "http://www.ncbi.nlm.nih.gov/pubmed/15289832", "http://www.ncbi.nlm.nih.gov/pubmed/22330137", "http://www.ncbi.nlm.nih.gov/pubmed/17196739", "http://www.ncbi.nlm.nih.gov/pubmed/23100393", "http://www.ncbi.nlm.nih.gov/pubmed/21678477", "http://www.ncbi.nlm.nih.gov/pubmed/20454457", "http://www.ncbi.nlm.nih.gov/pubmed/17965599" ], "ideal_answer": [ "Yes. It has been demonstrated in a number of experimental studies that DNA (Cytosine-5-)-methyltransferases (DNMT1, DNMT3A and DNMT3B) are deregulated in several types of cancer (invasive cervical cancer, colon cancer, esophageal squamous cell carcinoma (ESCC), gastric cancer, embryonal carcinoma, cervical cancer, adenoma, adenoid cystic carcinoma, salivary gland neoplasms). Moreover, three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region have been reported to be stratification markers that can predict an individual's susceptibility to cancers. Therefore, DNA (Cytosine-5-)-methyltransferases can serve as tumour markers." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248" ], "type": "yesno", "id": "5162e9df298dcd4e5100004b", "snippets": [ { "offsetInBeginSection": 226, "offsetInEndSection": 398, "text": "Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the inhibition of metastasis by DNMT3B interference.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22330137", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "This study was designed to determine the significance of DNA methyltransferases (DNMTs) in DNA hypermethylation in esophageal squamous cell carcinoma (ESCC) and to identify DNA methylation markers in serum for the early diagnosis of ESCC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150312", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "DNA methyltransferase 1 as a predictive biomarker and potential therapeutic target for chemotherapy in gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458988", "endSection": "title" }, { "offsetInBeginSection": 178, "offsetInEndSection": 342, "text": "We examined the prognostic and predictive impact of DNA methyltransferase (DNMT) 1 and 3b expression in gastric carcinomas (GC) treated by neoadjuvant chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458988", "endSection": "sections.0" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1072, "text": "High DNMT1 and DNMT3b expression was found in 105/127 (83%) and 79/127 (62%) carcinomas, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458988", "endSection": "sections.0" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1132, "text": "Tumoral DNMT3b mRNA up-regulation was significantly correlated with hypermethylation of multiple tumor-related genes (P=0.021).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150312", "endSection": "sections.0" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1406, "text": "A regulator of de novo DNA methyltransferases DNMT3A and DNMT3B, DNMT3L promoter was found to have lost DNA methylation to varying levels in 14 out of 15 cancer cervix samples analysed. The present study highlights the importance of DNA methylation profile at DNMT3L promoter not only as a promising biomarker for cervical cancer, which is the second most common cancer among women worldwide, but also provides insight into the possible role of DNMT3L in cancer development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17965599", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "DNMT3L is a novel marker and is essential for the growth of human embryonal carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20460473", "endSection": "title" }, { "offsetInBeginSection": 753, "offsetInEndSection": 1040, "text": "Among the DNMT genes, we found that mRNA for DNMT3L was specifically expressed in TGCTs, but neither in normal testicular tissues nor in cancer cells of somatic tissue origin. DNMT3L protein was strongly expressed in two EC cell lines, but not in the cell lines of somatic tissue origin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20460473", "endSection": "sections.0" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1297, "text": "Positive nuclear labeling for DNMT3a was found only in few neoplasms: 1 pleomorphic adenoma (9.0%), 2 adenoid cystic carcinoma (16.6%) and 1 mucoepidermoid (9.0%) cases. CONCLUSIONS: Our results were not able to demonstrate a clear correlation between DNMT1 and DNMT3a immunoexpression and salivary gland neoplasms development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19468253", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "DNA methylation, mediated by the combined action of three DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), is essential for mammalian development and is a major contributor to cellular transformation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23177624", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22490330", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "The recent identification of DNMT3A mutations in de novo acute myeloid leukemia prompted us to determine their frequency, patterns and clinical impact in a cohort of 98 patients with either therapy-related or secondary acute myeloid leukemia developing from an antecedent hematologic disorder.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993668", "endSection": "sections.0" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1132, "text": "DNA methyltransferases (DNMT1 and DNMT3b) were also decreased in vorinostat-treated A549 cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21678477", "endSection": "sections.0" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1314, "text": "To identify the mechanisms responsible for these genome-wide DNA methylation alterations, we measured the gene expression levels of several DNA methyltransferases (DNMTs) and their interacting proteins by TaqMan qPCR and observed increased expression of DNMT3A2, DNMT3B, and EZH2 in tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21521786", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "DNA methyltransferase 1 (DNMT1) is the primary enzyme that maintains DNA methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21045206", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "5-Azactydine inhibits cell growth by direct cytotoxic action as well as by inhibition of DNA methyl transferase enzyme.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19723570", "endSection": "sections.0" }, { "offsetInBeginSection": 384, "offsetInEndSection": 729, "text": "Alterations in metabolism of methyl donors, disturbances in activity and/or expression of DNA methyltransferases, and presence of DNA single-strand breaks could contribute to the loss of cytosine methylation during carcinogenesis; however, the precise mechanisms of genomic hypomethylation induced by chemical carcinogens remain largely unknown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18639561", "endSection": "sections.0" }, { "offsetInBeginSection": 145, "offsetInEndSection": 383, "text": "Recently, three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T (-149C>T), -283T>C, and -579G>T have also been reported to be stratification markers that can predict an individual's susceptibility to cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18097598", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Aberrant DNA methylation has been shown to play important roles during multistage carcinogenesis in various human organs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17196739", "endSection": "sections.0" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1092, "text": "Thus, tumour subsets exist that display concurrent decreased BRCA1 expression, BRCA1 promoter methylation, cytoplasmic CTCF expression and with DNMT3b over-expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17071074", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "DNA methylation patterns in genome are maintained during replication by a DNA methyltransferase Dnmt1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046852", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Aberrant DNA methylation has been shown to play an important role during multistage carcinogenesis in various human organs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16053511", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "To investigate the relationship between the expression of DNMT and clinical prognosis in adult patients with acute leukemia (AL), the mRNA expressions of DNMT, p15(INK4B), mdr1 were measured in 72 AL patients and 20 normal controls by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR); the ratio of p15 CpG land methylation was measured in 56 AL patients and 14 normal controls by methylation-specific PCR (MSP-PCR).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15854288", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "DNA methyltransferase Dnmt1 ensures clonal transmission of lineage-specific DNA methylation patterns in a mammalian genome during replication.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15509558", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Overexpression of the major DNA methyltransferase Dnmt1 is cytotoxic and has been hypothesized to result in aberrant hypermethylation of genes required for cell survival.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15499388", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "DNA (cytosine-5-)-methyltransferase 1 (DNMT1) plays an important role in the maintenance of DNA methylation patterns via complicated networks including signaling pathways and transcriptional factors, relating to cell differentiation or carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15289832", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "We evaluated the significance of aberrant DNA methyltransferase 1 (DNMT1) protein expression during gastric carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14742272", "endSection": "sections.0" } ] }, { "body": "Which RNA polymerase is used for the replication of viroids?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11713308", "http://www.ncbi.nlm.nih.gov/pubmed/6896006", "http://www.ncbi.nlm.nih.gov/pubmed/1733098", "http://www.ncbi.nlm.nih.gov/pubmed/10664390", "http://www.ncbi.nlm.nih.gov/pubmed/10668797", "http://www.ncbi.nlm.nih.gov/pubmed/6760914", "http://www.ncbi.nlm.nih.gov/pubmed/16912306", "http://www.ncbi.nlm.nih.gov/pubmed/22422064", "http://www.ncbi.nlm.nih.gov/pubmed/7231549", "http://www.ncbi.nlm.nih.gov/pubmed/16593489", "http://www.ncbi.nlm.nih.gov/pubmed/16406459" ], "ideal_answer": [ "DNA-dependent RNA polymerase II of plant origin transcribes viroid RNA into full-length copies", "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro. The RNA genome of potato spindle tuber viroid (PSTV) is transcribed in vitro into complementary DNA and RNA by DNA-dependent DNA polymerase I and RNA polymerase, respectively, from Escherichia coli. Host DNA-dependent RNA polymerase II (RNAP II) was proposed to be critical for its replication, but no interaction site for RNAP II on the PSTVd RNA genome was identified. Whereas maximum total activity was observed in 1 mM Mn(2+) with a pronounced reduction (80%) in 5 mM Mn(2+), CEV synthesis was maintained in 1-15 mM Mn(2+).", "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro. Research results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV." ], "exact_answer": [ [ "DNA-dependent RNA polymerase II" ], [ "RNA polymerase II" ], [ "RNAP II" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014772" ], "type": "list", "id": "56f24fec2ac5ed1459000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "DNA-dependent RNA polymerase II of plant origin transcribes viroid RNA into full-length copies", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7231549", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7231549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Viroid RNA is accepted as a template for in vitro transcription by DNA-dependent DNA polymerase I and RNA polymerase from Escherichia coli", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6760914", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The RNA genome of potato spindle tuber viroid (PSTV) is transcribed in vitro into complementary DNA and RNA by DNA-dependent DNA polymerase I and RNA polymerase, respectively, from Escherichia coli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6760914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "In vitro transcription of viroid RNA into full-length copies by RNA-dependent RNA polymerase from healthy tomato leaf tissue", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6896006", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "RNA-dependent RNA polymerase from healthy tomato plant tissue accepts potato spindle tuber viroid (PSTV) RNA as a template for the in vitro synthesis of full-length RNA copies of the PSTV genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6896006", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 823, "text": "Whereas maximum total activity was observed in 1 mM Mn(2+) with a pronounced reduction (80%) in 5 mM Mn(2+), CEV synthesis was maintained in 1-15 mM Mn(2+). Inhibition of alpha-amanitin-sensitive CEV synthesis in 200 mM (NH(4))(2)SO(4) resembles the reaction of RNA polymerase II on a free nucleic acid template", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16593489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Citrus exocortis viroid RNA is associated with the largest subunit of RNA polymerase II in tomato in vivo.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664390", "endSection": "title" }, { "offsetInBeginSection": 498, "offsetInEndSection": 672, "text": "The results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Transcription of potato spindle tuber viroid by RNA polymerase II starts predominantly at two specific sites", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11713308", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Pospiviroidae, with their main representative potato spindle tuber viroid (PSTVd), are replicated via a rolling circle mechanism by the host-encoded DNA-dependent RNA polymerase II (pol II)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11713308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Transcription of potato spindle tuber viroid by RNA polymerase II starts in the left terminal loop", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16406459", "endSection": "title" }, { "offsetInBeginSection": 144, "offsetInEndSection": 322, "text": "Viroids of the family Pospiviroidae, of which potato spindle tuber viroid (PSTVd) is the type strain, are replicated by the host's DNA-dependent RNA polymerase II in the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16406459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Tomato RNA polymerase II interacts with the rod-like conformation of the left terminal domain of the potato spindle tuber viroid positive RNA genome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22422064", "endSection": "title" }, { "offsetInBeginSection": 100, "offsetInEndSection": 272, "text": "Host DNA-dependent RNA polymerase II (RNAP II) was proposed to be critical for its replication, but no interaction site for RNAP II on the PSTVd RNA genome was identified. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22422064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "RNA polymerase II is implicated in the RNA-templated RNA synthesis during replication of viroids and Hepatitis Delta Virus (HDV); however, neither the RNA template nor protein factor requirements for this process are well defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10668797", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 532, "text": "Viroids of the Pospiviroidae family, as represented by the Potato spindle tuber viroid (PSTVd), replicate in the nucleus by utilizing DNA-dependent RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16912306", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 843, "text": "The results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664390", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1061, "text": "These results suggest that either RNA polymerase I or an unidentified RNA polymerase activity resistant to alpha-amanitin, acting on an RNA template, plays a role in the replication of ASBV, whereas for the rest of the viroids studied so far it appears that RNA polymerase II is involved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1733098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "RNA polymerase II is implicated in the RNA-templated RNA synthesis during replication of viroids and Hepatitis Delta Virus (HDV); however, neither the RNA template nor protein factor requirements for this process are well defined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10668797", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 326, "text": "Viroids of the family Pospiviroidae, of which potato spindle tuber viroid (PSTVd) is the type strain, are replicated by the host's DNA-dependent RNA polymerase II in the nucleus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16406459", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 369, "text": "Viroids of the Pospiviroidae family, as represented by the Potato spindle tuber viroid (PSTVd), replicate in the nucleus by utilizing DNA-dependent RNA polymerase II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16912306", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1063, "text": "These results suggest that either RNA polymerase I or an unidentified RNA polymerase activity resistant to alpha-amanitin, acting on an RNA template, plays a role in the replication of ASBV, whereas for the rest of the viroids studied so far it appears that RNA polymerase II is involved. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1733098", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 1063, "text": "Inhibition studies with alpha-amanitin showed that the synthesis of ASBV-specific RNAs was not affected by concentrations of 1 and 200 micrograms/ml of the drug, which typically inhibit RNA polymerase II and III, respectively, from most animal and plant systems. These results suggest that either RNA polymerase I or an unidentified RNA polymerase activity resistant to alpha-amanitin, acting on an RNA template, plays a role in the replication of ASBV, whereas for the rest of the viroids studied so far it appears that RNA polymerase II is involved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1733098", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 673, "text": "Nucleoprotein complexes in the soluble fraction which bound to a monoclonal antibody to the carboxy terminal domain of the largest subunit of RNA polymerase II (8WG16) were affinity purified and contained plus- and minus-sense CEV RNA. The results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664390", "endSection": "abstract" } ] }, { "body": "List Parkin binding partners", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21437181", "http://www.ncbi.nlm.nih.gov/pubmed/20064468", "http://www.ncbi.nlm.nih.gov/pubmed/18623069", "http://www.ncbi.nlm.nih.gov/pubmed/24244333", "http://www.ncbi.nlm.nih.gov/pubmed/15987638", "http://www.ncbi.nlm.nih.gov/pubmed/14579121", "http://www.ncbi.nlm.nih.gov/pubmed/17553932", "http://www.ncbi.nlm.nih.gov/pubmed/17229476", "http://www.ncbi.nlm.nih.gov/pubmed/18190519", "http://www.ncbi.nlm.nih.gov/pubmed/16842202", "http://www.ncbi.nlm.nih.gov/pubmed/16714300" ], "ideal_answer": [ "HSP90\nCDC37\nGRP75\nHSP60\nLRPPRC\nTUFM\nPICK1\nPSMA7\nPael receptor" ], "exact_answer": [ [ "HSP90" ], [ "CDC37" ], [ "GRP75" ], [ "HSP60" ], [ "LRPPRC" ], [ "TUFM" ], [ "PICK1" ], [ "PSMA7", "XAPC7" ], [ "Pael receptor" ] ], "concepts": [ "http://www.uniprot.org/uniprot/PRKN2_HUMAN" ], "type": "list", "id": "5318380bb166e2b806000013", "snippets": [ { "offsetInBeginSection": 482, "offsetInEndSection": 666, "text": "In addition to two known binding partners (HSP90, CDC37), 12 proteins were identified using the TAP assay; four of which are mitochondrially localized (GRP75, HSP60, LRPPRC, and TUFM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21437181", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 595, "text": "We find that parkin binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17553932", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 416, "text": "We have identified the 20S proteasomal subunit alpha4 (synonyms: PSMA7, XAPC7, subunit alpha type 7) as a new interacting partner of parkin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15987638", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 569, "text": "we cloned parkin-binding protein using a yeast two-hybrid system and identified a putative G protein-coupled receptor protein,which we named the Pael receptor (Pael-R)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14579121", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 735, "text": ", whose interactions with CASK are reviewed here, include the Parkinson's disease molecule parkin, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16842202", "endSection": "abstract" } ] }, { "body": "What is generic name of drug Adempas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24218053", "http://www.ncbi.nlm.nih.gov/pubmed/25395817", "http://www.ncbi.nlm.nih.gov/pubmed/24524094", "http://www.ncbi.nlm.nih.gov/pubmed/24391396", "http://www.ncbi.nlm.nih.gov/pubmed/25352393" ], "ideal_answer": [ "Riociguat is generic name of drug Adempas. It is a soluble guanylate cyclase stimulator that was approved for the treatment of patients with chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension." ], "exact_answer": [ "riociguat" ], "type": "factoid", "id": "54e1bdacae9738404b000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25395817", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Riociguat (Adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25395817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Riociguat (Adempas(\u00ae)), a soluble guanylate cyclase stimulator, is a new, first-in-class drug approved for the treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) [inoperable or persistent/recurrent following surgery] or pulmonary arterial hypertension (PAH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25352393", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 516, "text": "On October 8, 2013, riociguat (Adempas\u00ae) became the first medication approved for multiple etiologies of PH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24524094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Duavee, an oral contraceptive; riociguat (Adempas) for two types of pulmonary hypertension; and macitentan (Opsumit) for pulmonary arterial hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24391396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "Riociguat (Adempas(\u00ae)), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc. for the treatment of adult patients with inoperable or chronic/persistent chronic thromboembolic pulmonary hypertension (CTEPH) and for the treatment of adult patients with pulmonary arterial hypertension (PAH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Riociguat (Adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25395817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Riociguat (Adempas(\u00ae)), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Duavee, an oral contraceptive; riociguat (Adempas) for two types of pulmonary hypertension; and macitentan (Opsumit) for pulmonary arterial hypertension", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24391396", "endSection": "abstract" } ] }, { "body": "What is known about Vancomycin dosing in neonates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21862473", "http://www.ncbi.nlm.nih.gov/pubmed/22488303", "http://www.ncbi.nlm.nih.gov/pubmed/11378679", "http://www.ncbi.nlm.nih.gov/pubmed/21455009", "http://www.ncbi.nlm.nih.gov/pubmed/10801244", "http://www.ncbi.nlm.nih.gov/pubmed/2630235", "http://www.ncbi.nlm.nih.gov/pubmed/21378399", "http://www.ncbi.nlm.nih.gov/pubmed/10103340", "http://www.ncbi.nlm.nih.gov/pubmed/3991250", "http://www.ncbi.nlm.nih.gov/pubmed/22892931" ], "ideal_answer": [ "Staphylococcus epidermis, including methicillin-resistant strains, are inhibited by vancomycin concentrations of 1-4 \u00b5g/ml. \nStaphylococcus pyogenes, Streptococcus pneumonia, and Streptococcus viridans are susceptible to 2 \u00b5g/ml vancomycin. \nBacillus spp. are inhibited by 2 \u00b5g/ml, Corynebacterium spp. by 0.04-3.1 \u00b5g/ml and Clostridium spp. by 0.39-6 \u00b5g/ml vancomycin. \nPeak and trough concentrations of vancomycin should be 40 \u03bcg/ml and 10 \u03bcg/ml, respectively, to both be effective and avoid oto- or nephrotoxicity in adults. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. Because vancomycin activity is primarily time-dependent, the 24-h area under the curve (AUC0-24h) divided by the minimum inhibitor concentration (MIC) value (AUC0-24h/MIC) is a better predictor of efficacy. In adults with MIC values less than 1 \u03bcg/ml, trough concentrations greater than 10 \u00b5g/ml result in AUC0-24h/MIC values 400\nCompared with adults, neonates have a higher extracellular fluid volume and a limited renal elimination capacity resulting in different pharmacokinetics subject to maturation stage. Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age. These differences alter the vancomycin dosing recommendations in these two groups of premature infants.\nVancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations 40 microg/mL. Vancomycin is associated with ototoxicity.\nThere is no consensus on vancomycin dosing in newborns and young infants, which leads to significant variation in vancomycin dosing regimens and TDM guidance across neonatal units. The development of standardized, evidence-based protocols should be prioritized." ], "concepts": [ "http://www.biosemantics.org/jochem#4272288", "http://www.biosemantics.org/jochem#4272290", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014640", "http://www.biosemantics.org/jochem#4022642", "http://www.biosemantics.org/jochem#4145076", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007231", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007234" ], "type": "summary", "id": "515d71ee298dcd4e5100000b", "snippets": [ { "offsetInBeginSection": 2117, "offsetInEndSection": 2534, "text": "Monte Carlo simulations based on our population pharmacokinetic model suggest that vancomycin dosing guidelines based on serum creatinine concentration have a greater likelihood of achieving trough concentrations in the 5-15-mg/L range compared with other evaluated dosing regimens. None of the four dosing regimens is suitable to produce target trough concentration of 15-20 mg/L in an acceptable number of patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488303", "endSection": "sections.0" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1039, "text": "There is significant variation in gentamicin and vancomycin dosing regimens and TDM guidance across a UK network of neonatal units. The development of standardized, evidence-based protocols should be prioritized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862473", "endSection": "sections.0" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1380, "text": "Vancomycin, by contrast, was associated with ototoxicity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21455009", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 85, "text": "There is no consensus on vancomycin dosing in newborns and young infants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21378399", "endSection": "sections.0" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1391, "text": "The modified regimen for a target vancomycin concentration of 25 mg/l consisted of a bolus of 20 mg/kg followed by continuous infusion of 30 mg/kg.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21378399", "endSection": "sections.0" }, { "offsetInBeginSection": 1767, "offsetInEndSection": 1857, "text": "There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11378679", "endSection": "sections.0" }, { "offsetInBeginSection": 1598, "offsetInEndSection": 1775, "text": "Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11378679", "endSection": "sections.0" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1879, "text": "Targets were a trough concentration between 5 and 15 mg/L and a peak below 40 mg/L. In the prospective study, the optimal scheme was tested in 22 patients. RESULTS: Of the 108 patients, 34.3% of measured trough concentrations and 17.6% of peak concentrations were outside the desired therapeutic range. The model that best fitted the data included clearance and volume per kilogram and was independent of gestational age. Simulation of various dosing schemes showed that a dosing schedule of 30 mg/kg/day, irrespective of gestational age, in three doses was optimal, and this scheme was prospectively tested. Mean trough concentrations before the second dose were 8.2 +/- 2.2 mg/L versus a predicted trough of 8.9 +/- 2.5 mg/L. No peak levels higher than 40 mg/L were found. CONCLUSIONS: The use of the proposed schedule leads to adequate vancomycin trough serum concentrations, and there is no need for routine monitoring of peak serum concentrations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10801244", "endSection": "sections.0" }, { "offsetInBeginSection": 2578, "offsetInEndSection": 2686, "text": "Vancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations >40 microg/mL.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10103340", "endSection": "sections.0" }, { "offsetInBeginSection": 68, "offsetInEndSection": 760, "text": "Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age. These differences alter the vancomycin dosing recommendations in these two groups of premature infants. We recommend initial dosage regimens consisting of a loading dose of vancomycin of 25 mg/kg followed by doses of 15 mg/kg every 12 hours for infants with weights less than 1,000 gm. Infants weighing over 1,000 gm should receive 10 mg/kg every 12 hours, with a loading dose of 12.5 mg/kg. Serum vancomycin concentration should be monitored, however, for final optimization of therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3991250", "endSection": "sections.0" } ] }, { "body": "Is single guide RNA part of the CRISPR/Cas9 tool or an inhibitor of its function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25161872", "http://www.ncbi.nlm.nih.gov/pubmed/25122746", "http://www.ncbi.nlm.nih.gov/pubmed/25048165", "http://www.ncbi.nlm.nih.gov/pubmed/25731961", "http://www.ncbi.nlm.nih.gov/pubmed/24870050", "http://www.ncbi.nlm.nih.gov/pubmed/23907171", "http://www.ncbi.nlm.nih.gov/pubmed/25713377", "http://www.ncbi.nlm.nih.gov/pubmed/24825012", "http://www.ncbi.nlm.nih.gov/pubmed/25398342", "http://www.ncbi.nlm.nih.gov/pubmed/25437567", "http://www.ncbi.nlm.nih.gov/pubmed/25274302", "http://www.ncbi.nlm.nih.gov/pubmed/24838573", "http://www.ncbi.nlm.nih.gov/pubmed/24710347", "http://www.ncbi.nlm.nih.gov/pubmed/24920971", "http://www.ncbi.nlm.nih.gov/pubmed/25239977" ], "ideal_answer": [ "Single guide RNA is part of the CRISPR/Cas9 system." ], "exact_answer": [ "Single guide RNA is part of the CRISPR/Cas9 system." ], "concepts": [ "http://www.uniprot.org/uniprot/CAS9_CAMJE", "http://www.uniprot.org/uniprot/CAS9_NEIMA", "http://www.uniprot.org/uniprot/CAS9_FRATN", "http://www.uniprot.org/uniprot/CAS9_STRTR", "http://www.uniprot.org/uniprot/CAS9_ACTNH", "http://www.uniprot.org/uniprot/CAS9_NEIM8", "http://www.uniprot.org/uniprot/CAS9_PASMU" ], "type": "factoid", "id": "56f146db2ac5ed145900000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "Cas9, an RNA-guided DNA endonuclease found in clustered regularly interspaced short palindromic repeats (CRISPR) bacterial immune systems, is a versatile tool for genome editing, transcriptional regulation, and cellular imaging applications. Structures of Streptococcus pyogenes Cas9 alone or bound to single-guide RNA (sgRNA) and target DNA revealed a bilobed protein architecture that undergoes major conformational changes upon guide RNA and DNA binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25713377", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 1042, "text": "Although the lobes do not interact on their own, the sgRNA recruits them into a ternary complex that recapitulates the activity of full-length Cas9 and catalyzes site-specific DNA cleavage. The use of a modified sgRNA abrogates split-Cas9 activity by preventing dimerization, allowing for the development of an inducible dimerization system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25713377", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 550, "text": "This new type of genetic library is constructed through the lentiviral delivery of single-guide RNA collections that direct Cas9 or inactive dead Cas9 fused with effectors to interrogate gene function or regulate gene transcription in targeted cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 382, "text": "The CRISPR/Cas9 system has recently emerged as a\u00a0powerful tool for functional genomic studies in Drosophila melanogaster. However, single-guide RNA (sgRNA) parameters affecting the specificity and efficiency of the system in flies are still not clear. Here, we found that off-target effects did not occur in regions of genomic DNA with three or more nucleotide mismatches to sgRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437567", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1050, "text": "Our work demonstrates a comprehensive optimization of sgRNA and promises to vastly simplify CRISPR/Cas9 experiments in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437567", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 928, "text": "Targeted genome engineering is expected to contribute significantly to future varietal improvement, and genome editing technologies using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9/single guide RNA (sgRNA) have already been successfully used to genetically modify plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24710347", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 707, "text": "A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25122746", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 937, "text": "To determine if the Cas9 and single guide RNA (sgRNA) genes were functional in C. reinhardtii, we tested the ability of a codon-optimized Cas9 gene along with one of four different sgRNAs to cause targeted gene disruption during a 24-h period immediately following transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25239977", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 635, "text": "Recently, compared to the wildtype nuclease, paired Cas9 nickase (Cas9n) combined with single guide RNA (sgRNA) molecules has been found to enhance the specificity of genome editing while reducing off-target effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25161872", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 761, "text": "Here we utilized a CRISPR/CAS9-based system with single guide RNAs to disrupt genes in T.\u00a0gondii.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825012", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1391, "text": "To address the need for uniform and sustained delivery of multiplex CRISPR/Cas9-based genome engineering tools, we developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four sgRNAs from independent RNA polymerase III promoters that are incorporated into the vector by a convenient Golden Gate cloning method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25122746", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 519, "text": "A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25122746", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 629, "text": "Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25048165", "endSection": "abstract" } ] }, { "body": "What is the target protein of the drug Idelalisib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24261963", "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "http://www.ncbi.nlm.nih.gov/pubmed/24085367", "http://www.ncbi.nlm.nih.gov/pubmed/23847354", "http://www.ncbi.nlm.nih.gov/pubmed/24014301", "http://www.ncbi.nlm.nih.gov/pubmed/24323900", "http://www.ncbi.nlm.nih.gov/pubmed/24009233", "http://www.ncbi.nlm.nih.gov/pubmed/24273091", "http://www.ncbi.nlm.nih.gov/pubmed/24060900" ], "ideal_answer": [ "Idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform." ], "exact_answer": [ "PI3K-\u03b4", "phosphoinositol-3 kinase delta isoform" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011955", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ], "type": "factoid", "id": "5321bc309b2d7acc7e00000d", "snippets": [ { "offsetInBeginSection": 1348, "offsetInEndSection": 1369, "text": " PI3K\u03b4 (idelalisib). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24323900", "endSection": "abstract" }, { "offsetInBeginSection": 1962, "offsetInEndSection": 1990, "text": "Idelalisib (PI3K inhibitor) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273091", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 656, "text": "In the last few years, several classes of potent and selective small molecule PI3K inhibitors have been developed, and at least fifteen compounds have progressed into clinical trials as new anticancer drugs. Among these, idelalisib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24261963", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1112, "text": " idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24085367", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 577, "text": "PI3K inhibitor idelalisib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24014301", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1211, "text": "the PI3K inhibitor idelalisib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24009233", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 64, "text": "PI3K-\u03b4 inhibitor idelalisib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23847354", "endSection": "abstract" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1077, "text": "idelalisib (GS-1101) -a specific isoform of the PI3K (PI3K) inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "endSection": "abstract" } ] }, { "body": "Which antiepileptic drug is most strongly associated with spina bifida? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3939491", "http://www.ncbi.nlm.nih.gov/pubmed/22051200", "http://www.ncbi.nlm.nih.gov/pubmed/8075508", "http://www.ncbi.nlm.nih.gov/pubmed/23082254", "http://www.ncbi.nlm.nih.gov/pubmed/10339792", "http://www.ncbi.nlm.nih.gov/pubmed/17075842", "http://www.ncbi.nlm.nih.gov/pubmed/19490036", "http://www.ncbi.nlm.nih.gov/pubmed/11077457", "http://www.ncbi.nlm.nih.gov/pubmed/2707392", "http://www.ncbi.nlm.nih.gov/pubmed/21766433" ], "ideal_answer": [ "Phenytoin is not used in pregnancy as it is associated with a severe fetal deformation. From the other anticonvulsants most studies report the higher association between use during pregnancy and spin bifida to occur with Valproate." ], "exact_answer": [ "Valproate" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0080016", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000927" ], "type": "factoid", "id": "51588bb2d24251bc05000091", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051200", "endSection": "sections.0" }, { "offsetInBeginSection": 721, "offsetInEndSection": 1062, "text": "The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0-21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3-9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3-7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1-4.5) in the United States.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21766433", "endSection": "sections.0" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1307, "text": "Increased risk for MCMs could be demonstrated only for exposure to valproate (5.6%, p = 0.005) and AED polytherapy (6.1%, p = 0.02). Neonatal spina bifida was not significantly increased, but was a major indication for elective pregnancy termination among women with epilepsy. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19490036", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Valproic acid, a drug commonly used to treat seizures and other psychiatric disorders, causes neural tube defects (NTDs) in exposed fetuses at a rate 20 times higher than in the general population. Failure of the neural tube to close during development results in exencephaly or anencephaly, as well as spina bifida.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17075842", "endSection": "sections.0" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1095, "text": "Associations were found for spina bifida with valproic acid. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11077457", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Fetal exposure to valproic acid or carbamazepine increases the risk of neural tube defect (NTD)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10339792", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 684, "text": "Women with epilepsy giving birth during 1973 to 1991 were identified by record linkage of Swedish health registries. Among 3,625 identified infants, 9 had spina bifida. A nested case-control study was performed, comparing drugs used in early pregnancy in the 9 cases and in 18 controls, matched for year of delivery, maternal age, and parity. Six of the spina bifida mothers had used carbamazepine and two had used valproic acid. Among the controls, 5 women used carbamazepine and one valproic acid. There is an apparent excess risk for spina bifida after use of either of these two drugs, but it is not statistically significant when the analysis is restricted to drug-using women. T", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8075508", "endSection": "sections.0" }, { "offsetInBeginSection": 459, "offsetInEndSection": 623, "text": "A significant association was seen between maternal use of valproic acid and spina bifida, and a weaker, non-significant one between carbamazepine and spina bifida.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2707392", "endSection": "sections.0" }, { "offsetInBeginSection": 768, "offsetInEndSection": 988, "text": "A statistically significant association between Spina Bifida and Valproic Acid (odds ratio 22.7; Fisher p value = 0.0364) was observed: no other anticonvulsant tested showed any association with any type of malformation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3939491", "endSection": "sections.0" } ] }, { "body": "Which bacteria caused plague?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8052312", "http://www.ncbi.nlm.nih.gov/pubmed/16410352" ], "ideal_answer": [ "Yersinia pestis is the causative bacteria of the plague." ], "exact_answer": [ "Yersinia pestis" ], "type": "factoid", "id": "571cdd227de986d80d00000f", "snippets": [ { "offsetInBeginSection": 187, "offsetInEndSection": 344, "text": " the causative bacteria Yersinia pestis as an agent of biological warfare have highlighted the need for a safe, efficacious, and rapidly producible vaccine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16410352", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 256, "text": "Yersinia, the causative bacteria of the bubonic plague and other enteric diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8052312", "endSection": "abstract" } ] }, { "body": "The drug JTV519 is derivative of which group of chemical compounds?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11429046", "http://www.ncbi.nlm.nih.gov/pubmed/11757794", "http://www.ncbi.nlm.nih.gov/pubmed/21989257", "http://www.ncbi.nlm.nih.gov/pubmed/17313373", "http://www.ncbi.nlm.nih.gov/pubmed/10683355", "http://www.ncbi.nlm.nih.gov/pubmed/10789707", "http://www.ncbi.nlm.nih.gov/pubmed/12433661", "http://www.ncbi.nlm.nih.gov/pubmed/23349825", "http://www.ncbi.nlm.nih.gov/pubmed/17112502", "http://www.ncbi.nlm.nih.gov/pubmed/15073377", "http://www.ncbi.nlm.nih.gov/pubmed/22509897", "http://www.ncbi.nlm.nih.gov/pubmed/12359358", "http://www.ncbi.nlm.nih.gov/pubmed/12551874", "http://www.ncbi.nlm.nih.gov/pubmed/10864882", "http://www.ncbi.nlm.nih.gov/pubmed/11101196" ], "ideal_answer": [ "The 1,4-benzothiazepine derivative JTV-519 is a new type of calcium ion channel modulator.JTV-519, which has potential use as an antiarrhythmic [285800]. The drug is a novel cardioprotectant derivative of 1,4-benzothiazepine for which phase I trials were completed in the third quarter of 1998", "JTV519 (K201), is a 1,4-benzothiazepine derivative and multi-channel blocker, which has been found to stabilize RyR2s and decrease SR Ca\u00b2\u207a leak." ], "exact_answer": [ "1,4-benzothiazepine", "benzothiazepine" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=chemicals_and_drugs_category", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004339" ], "type": "factoid", "id": "54f9b74306d9727f76000004", "snippets": [ { "offsetInBeginSection": 202, "offsetInEndSection": 341, "text": "In these conditions, JTV519 (K201), a 1,4-benzothiazepine derivative and multi-channel blocker, stabilizes RyR2s and decrease SR Ca\u00b2\u207a leak.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22509897", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 514, "text": "The 1,4-benzothiazepine derivative JTV519, and the more specific derivative S107 (2,3,4,5,-tetrahydro-7-methoxy-4-methyl-1,4-benzothiazepine), are thought to improve skeletal muscle function by stabilizing the RyR1-FKBP12 complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349825", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 491, "text": "In this article, we synthesize derivatives of the channel activator 4-chloro-3-methyl phenol (4-CmC) and the 1,4-benzothiazepine channel inhibitor 4-[-3{1-(4-benzyl) piperidinyl}propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine (K201, JTV519) with enhanced electron donor properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21989257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "K201 (JTV519), a benzothiazepine derivative, has been shown to possess anti-arrhythmic and cardioprotective properties, but the mechanism of its action is both complex and controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17313373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "K201 (JTV519) is a 1,4-benzothiazepine derivative that exhibits a strong cardioprotective action and acts as a multiple-channel blocker, including as a K+ channel blocker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17112502", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 644, "text": "A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak that triggers arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15073377", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 396, "text": "We report that a new drug, the 1,4-benzothiazepine derivative JTV519, reverses this pathogenic process. JTV519 is known to have a protective effect against Ca2+ overload-induced myocardial injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12551874", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1066, "text": "In conclusion, JTV519, a new 1,4-benzothiazepine derivative, corrected the defective channel gating in RyR (increase in both the rapid conformational change and the subsequent Ca(2+) release rate) in HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12433661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "A newly synthesized 1,4-benzothiazipine derivate, 4-[3-(4-benzylpiperidin-1-yl) propionyl]-7-methoxy-2,3,4,5-tetrahydro-1, 4-benzothiazepine monohydrochloride (JTV-519) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) mediated multidrug resistance (MDR) in K562/MDR and KB/MRP cells, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12359358", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 269, "text": "JTV-519, which has potential use as an antiarrhythmic [285800]. The drug is a novel cardioprotectant derivative of 1,4-benzothiazepine for which phase I trials were completed in the third quarter of 1998", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11757794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The 1,4-benzothiazepine derivative JTV-519 is a new type of calcium ion channel modulator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11429046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "A new 1,4-benzothiazepine derivative, JTV519 (JTV), has strong protective effects against isoproterenol-induced myocardial injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11101196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A newly synthesized benzothiazepine derivative, JTV-519 (JT) has been reported to be cardioprotective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10864882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Protective effect of JTV519, a new 1,4-benzothiazepine derivative, on prolonged myocardial preservation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10789707", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 139, "text": "A new 1,4-benzothiazepine derivative, JTV519, has a strong protective effect against Ca(2+) overload-induced myocardial injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10683355", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 289, "text": " We report that a new drug, the 1,4-benzothiazepine derivative JTV519, reverses this pathogenic process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12551874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Protective effect of JTV519, a new 1,4-benzothiazepine derivative, on prolonged myocardial preservation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10789707", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "A new 1,4-benzothiazepine derivative, JTV519 (JTV), has strong protective effects against isoproterenol-induced myocardial injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11101196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A new 1,4-benzothiazepine derivative, JTV519, has a strong protective effect against Ca(2+) overload-induced myocardial injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10683355", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 315, "text": " In these conditions, JTV519 (K201), a 1,4-benzothiazepine derivative and multi-channel blocker, stabilizes RyR2s and decrease SR Ca?\u207a leak.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22509897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The cardioprotective effects of a new 1,4-benzothiazepine derivative, JTV519, on ischemia/reperfusion-induced Ca2+ overload in isolated rat hearts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11101196", "endSection": "title" }, { "offsetInBeginSection": 188, "offsetInEndSection": 290, "text": "We report that a new drug, the 1,4-benzothiazepine derivative JTV519, reverses this pathogenic process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12551874", "endSection": "abstract" } ] }, { "body": "Is the long non- coding RNA malat-1 up or downregulated in cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16441420", "http://www.ncbi.nlm.nih.gov/pubmed/21266177", "http://www.ncbi.nlm.nih.gov/pubmed/22722759", "http://www.ncbi.nlm.nih.gov/pubmed/15552795", "http://www.ncbi.nlm.nih.gov/pubmed/24163781", "http://www.ncbi.nlm.nih.gov/pubmed/18006640", "http://www.ncbi.nlm.nih.gov/pubmed/23726266", "http://www.ncbi.nlm.nih.gov/pubmed/16878148", "http://www.ncbi.nlm.nih.gov/pubmed/12970751", "http://www.ncbi.nlm.nih.gov/pubmed/23845456", "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "http://www.ncbi.nlm.nih.gov/pubmed/23104528", "http://www.ncbi.nlm.nih.gov/pubmed/21678027", "http://www.ncbi.nlm.nih.gov/pubmed/22088988" ], "ideal_answer": [ "Malat-1 expression is upregulated in several tumor types" ], "exact_answer": [ "upregulated" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022661" ], "type": "factoid", "id": "53440d2caeec6fbd07000004", "snippets": [ { "offsetInBeginSection": 132, "offsetInEndSection": 188, "text": "lncRNA MALAT-1 expression is upregulated in some tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722759", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 225, "text": "Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) is an ncRNA that is highly expressed in several tumor types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088988", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 158, "text": "metastasis-associated lung adenocarcinoma transcript (MALAT)-1 is known to be consistently upregulated in several epithelial malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163781", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1048, "text": "MALAT-1 was up-regulated in human prostate cancer tissues and cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845456", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1043, "text": "Genome-wide profiling revealed that MALAT-1 and prostate cancer gene 3 (PCA3) are overexpressed in PCa tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23726266", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1131, "text": "The level of MALAT-1 in LSCC was significantly higher than that in the corresponding adjacent non-neoplastic tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104528", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 189, "text": "metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 185, "text": "(MALAT1), a long non-coding RNA (lncRNA), is up-regulated in many solid tumors and associated with cancer metastasis and recurrence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21678027", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 715, "text": " Quantitative analyses indicated a 6-7-fold increased RNA level in HCCs versus uninvolved liver,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16878148", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 335, "text": "(hcn), encoding a 7-kb mRNA-like transcript. The gene appears to be the murine ortholog of the human alpha gene, that is, MALAT-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16878148", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 532, "text": "After suppression subtractive hybridization and differential screening, we detected the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene as one of the major genes upregulated in ESS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16441420", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1117, "text": "a novel non-coding RNA (MALAT-1) to be expressed at significantly higher levels in stage-I and stage-II NSCLC primary tumours that subsequently metastasised", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15552795", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 635, "text": "quantitative RT-PCR verified overexpression in metastasizing samples. Several of the identified genes (eIF4A1, thymosin beta4 and a novel transcript named MALAT-1) were demonstrated to be significantly associated with metastasis in NSCLC patients ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12970751", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 289, "text": "\u03a3 RNA is a class of conserved large non-coding RNAs (murine Hepcarcin; human MALAT-1) up-regulated in carcinomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21266177", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 415, "text": "To date, most known NCTs studied have been relatively short, but several important regulatory NCTs, including XIST, MALAT-1, BC1 and BC200, are considerably larger in length", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006640", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1364, "text": "These NCTs were among the most abundantly expressed transcripts detected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006640", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 642, "text": "The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "endSection": "abstract" } ] }, { "body": "Oxantel is used for periodontitis treatment. How does it work?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20038616", "http://www.ncbi.nlm.nih.gov/pubmed/24165189" ], "triples": [ { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/oxantel", "o": "36531-26-7" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/oxantel", "o": "oxantel" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0294401", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0163908", "o": "http://linkedlifedata.com/resource/umls/label/A0294401" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0294401", "o": "oxantel pamoate" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0163908", "o": "http://linkedlifedata.com/resource/umls/label/A0294401" } ], "ideal_answer": [ "Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms." ], "exact_answer": [ "Oxantel disrupts polymicrobial biofilm" ], "concepts": [ "http://www.biosemantics.org/jochem#4251142", "http://www.disease-ontology.org/api/metadata/DOID:824", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010518" ], "type": "factoid", "id": "530c7f52970c65fa6b000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Oxantel disrupts polymicrobial biofilm development of periodontal pathogens", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165189", "endSection": "title" }, { "offsetInBeginSection": 273, "offsetInEndSection": 444, "text": "he anthelmintic drug oxantel has been shown to inhibit fumarate reductase (Frd) activity in some pathogenic bacteria and inhibit P. gingivalis homotypic biofilm formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165189", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 349, "text": "Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms at concentrations below its MIC against planktonic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038616", "endSection": "abstract" } ] }, { "body": "What is apelin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25362565", "http://www.ncbi.nlm.nih.gov/pubmed/25486928", "http://www.ncbi.nlm.nih.gov/pubmed/25380625", "http://www.ncbi.nlm.nih.gov/pubmed/25711427", "http://www.ncbi.nlm.nih.gov/pubmed/25931124", "http://www.ncbi.nlm.nih.gov/pubmed/25965959", "http://www.ncbi.nlm.nih.gov/pubmed/25668242", "http://www.ncbi.nlm.nih.gov/pubmed/25491175", "http://www.ncbi.nlm.nih.gov/pubmed/26491547", "http://www.ncbi.nlm.nih.gov/pubmed/26149233" ], "ideal_answer": [ "Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor." ], "exact_answer": [ "Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor." ], "type": "factoid", "id": "56e6dfc2edfc094c1f000003", "snippets": [ { "offsetInBeginSection": 115, "offsetInEndSection": 215, "text": "Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25965959", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 334, "text": "Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25931124", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 248, "text": "Apelin, as the endogenous ligand of G protein-coupled receptor APJ, participates in a number of physiological and pathological processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26491547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Apelin is a novel bioactive peptide as the endogenous ligand for APJ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149233", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 53, "text": "adipokine apelin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25491175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Apelin is the endogenous ligand of the APJ receptor, a member of the G protein-coupled receptor family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25668242", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1019, "text": "To date four adipokines (leptin, visfatin, apelin and ghrelin) have been investigated and all affect myometrial contractility, but some more potently than others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25711427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The adipocytokine apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous and cardiovascular systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25362565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The aim of this study was to determine the levels of regulatory peptides apelin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25380625", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 432, "text": "Apelin is a vaso-dilatory peptide that also has a modulatory role in pain processing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25486928", "endSection": "abstract" } ] }, { "body": "What is the function of the protein encoded by the gene PABPC4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23938467", "http://www.ncbi.nlm.nih.gov/pubmed/22884093", "http://www.ncbi.nlm.nih.gov/pubmed/21300955", "http://www.ncbi.nlm.nih.gov/pubmed/23300856", "http://www.ncbi.nlm.nih.gov/pubmed/21940797", "http://www.ncbi.nlm.nih.gov/pubmed/20943973", "http://www.ncbi.nlm.nih.gov/pubmed/11328870", "http://www.ncbi.nlm.nih.gov/pubmed/22530058", "http://www.ncbi.nlm.nih.gov/pubmed/22896784", "http://www.ncbi.nlm.nih.gov/pubmed/23181716" ], "triples": [ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/P21187", "o": "true" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5032313138370015", "o": "Poly(A)-binding protein" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-103658", "o": "pAbp" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/intact/EBI-103658", "o": "http://purl.uniprot.org/uniprot/P21187" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5032313138370015", "o": "Polyadenylate-binding protein" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P21187", "o": "http://linkedlifedata.com/resource/#_5032313138370015" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5032313138370015", "o": "PABP" } ], "ideal_answer": [ "The main function of PABPC4 is in mRNA stability and translation initiation. PABPC4 may also play a role in chronic inflammation and in the pathogenesis of colorectal cancer." ], "exact_answer": [ "PABC4 is important for mRNA stability and translation initiation, in chronic inflammation and in the pathogenesis of colorectal cancer." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006378", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026723", "http://www.uniprot.org/uniprot/PABP_DROME", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002352", "http://www.uniprot.org/uniprot/PABP4_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011485", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043631", "http://www.biosemantics.org/jochem#4249823", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005515", "http://www.biosemantics.org/jochem#4002540", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008143" ], "type": "factoid", "id": "531d744c267d7dd053000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "In testis mRNA stability and translation initiation are extensively under the control of poly(A)-binding proteins (PABP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11328870", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1081, "text": "Taken together, our findings indicate that PABPC4 may play a role in the pathogenesis of colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884093", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1447, "text": "Consistent with these biochemical activities, plus corresponding histological profiles, the identified RNA processing factors are predicted to collectively drive post-transcriptional expression of an alternative exome that fuels finishing steps of sperm maturation and fitness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23938467", "endSection": "abstract" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1719, "text": "This is the first evidence that PABPCs have a targeted role in hTERT regulation leading to a growth advantage in cells expressing HPV16 E6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20943973", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 953, "text": "to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300955", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 495, "text": "and with the exception of PABP4, appear to be restricted in their expression to a small number of cell types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21940797", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1493, "text": "PABPC4 (p(Het) = 0.034) for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22530058", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1115, "text": "In addition, PABP4 was associated with the poly(A) tract of pre-mRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300856", "endSection": "abstract" } ] }, { "body": "What kind of enzyme is encoded by the proto-oncogene ABL1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19290927", "http://www.ncbi.nlm.nih.gov/pubmed/20841568", "http://www.ncbi.nlm.nih.gov/pubmed/23842646", "http://www.ncbi.nlm.nih.gov/pubmed/19794087", "http://www.ncbi.nlm.nih.gov/pubmed/18528425", "http://www.ncbi.nlm.nih.gov/pubmed/12796783", "http://www.ncbi.nlm.nih.gov/pubmed/9500553", "http://www.ncbi.nlm.nih.gov/pubmed/21435002", "http://www.ncbi.nlm.nih.gov/pubmed/18796434", "http://www.ncbi.nlm.nih.gov/pubmed/24012954" ], "ideal_answer": [ "ABL-family proteins comprise one of the best conserved branches of the tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ", "The Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, transduces diverse extracellular signals to protein networks that control proliferation, survival, migration and invasion. Constitutively activated mutants of the non-receptor tyrosine kinase (TK) ABL1 (Abelson murine leukemia viral (v-abl) homolog (1) protein) play a central role in the pathogenesis myeloproliferative disorders and in some cases of acute leukemia and lymphoma." ], "exact_answer": [ "Nonreceptor tyrosine kinase", "Protein-Tyrosine Kinase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011519", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011518" ], "type": "factoid", "id": "55241f9e2c8b63434a000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "The Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, transduces diverse extracellular signals to protein networks that control proliferation, survival, migration and invasion. ABL1 was first identified as an oncogene required for the development of leukaemias initiated by retroviruses or chromosome translocations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23842646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 613, "text": "Chromosomal rearrangements involving the ABL1 gene, leading to a BCR-ABL1 fusion gene, have been mainly associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia (ALL). At present, six other genes have been shown to fuse to ABL1. The kinase domain of ABL1 is retained in all chimeric proteins that are also composed of the N-terminal part of the partner protein that often includes a coiled-coil or a helix-loop-helix domain. These latter domains allow oligomerization of the protein that is required for tyrosine kinase activation, cytoskeletal localization, and neoplastic transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 543, "text": "ABL-family proteins comprise one of the best conserved branches of the tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20841568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 857, "text": "Protein tyrosine kinases form a large family of signaling proteins implicated in both normal and malignant cell signaling. The aim of this study was to identify protein tyro-sine kinases that can transform hematopoietic cells to growth factor independent proliferation when constitutively activated by homodimerization. We used a modified retroviral insertion mutagenesis screen with a retroviral vector containing the homodimerization domain of ETV6 followed by an artificial splice donor site. Integration of this retroviral vector within a gene of the host genome would generate a fusion transcript containing the dimerization domain and part of the disrupted gene. Using this strategy with the IL3 dependent Ba/F3 cell line, we identified 8 different protein tyrosine kinases (Abl1, Fgfr1, Hck, Jak2, Lck, Mertk, Mst1r, Tnk1) that transformed the cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19794087", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 952, "text": "Three families of tyrosine kinases have long been recognized to play critical roles in TCR-dependent signaling. They are the Src, zeta-associated protein of 70 kDa, and Tec families of kinases. More recently, the Abelson (Abl) tyrosine kinases have been shown to be activated by TCR engagement and to be required for maximal TCR signaling. Using T-cell conditional knockout mice deficient for Abl family kinases, Abl (Abl1) and Abl-related gene (Arg) (Abl2), it was recently shown that loss of Abl kinases results in defective T-cell development and a partial block in the transition to the CD4(+)CD8(+) stage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19290927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "ABL family tyrosine kinases are tightly regulated by autoinhibition and phosphorylation mechanisms. These kinases maintain an inactive conformation through intramolecular interactions involving SH3 and SH2 domains. RIN1, a downstream effector of RAS, binds to the ABL SH3 and SH2 domains and stimulates ABL tyrosine kinase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18796434", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 471, "text": "RIN1 binding to the ABL2 kinase resulted in a large decrease in Km and a small increase in Vmax toward an ABL consensus substrate peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18796434", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 1036, "text": "RIN1 increased the kinase activity of both ABL1 and ABL2, and this occurred in the presence or absence of ABL regulatory domains outside the SH3-SH2-tyrosine kinase domain core.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18796434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "Constitutively activated mutants of the non-receptor tyrosine kinases (TK) ABL1 (Abelson murine leukemia viral (v-abl) homolog (1) protein) and JAK2 (JAnus Kinase 2 or Just Another Kinase 2) play a central role in the pathogenesis of clinically and morphologically distinct chronic myeloproliferative disorders but are also found in some cases of de novo acute leukemia and lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18528425", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 639, "text": "Abl1 (previously known as Abl) and the Abl1-related gene product Abl2 (previously known as Arg) define a family of tyrosine kinases that regulate actin structure and presynaptic axon guidance. Here we show that the Abl kinases are critical mediators of postsynaptic assembly downstream of agrin and MuSK. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12796783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase (c-Abl) that has been implicated in processes of cell differentiation, cell division, cell adhesion and stress response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9500553", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 723, "text": "Two essential proteins, Proto-oncogene tyrosine-protein kinase ABL1 (c-ABL) and Heat shock 70kDa protein 4 (Apg-2), were confirmed by Western blot and showed consistent changes with proteomic results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24012954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase (c-Abl) that has been implicated in processes of cell differentiation, cell division, cell adhesion and stress response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9500553", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of Romano Ward long QT syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7994803", "http://www.ncbi.nlm.nih.gov/pubmed/10593671", "http://www.ncbi.nlm.nih.gov/pubmed/8048706", "http://www.ncbi.nlm.nih.gov/pubmed/8098062", "http://www.ncbi.nlm.nih.gov/pubmed/19862833", "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "http://www.ncbi.nlm.nih.gov/pubmed/8223759", "http://www.ncbi.nlm.nih.gov/pubmed/2771275", "http://www.ncbi.nlm.nih.gov/pubmed/7695867", "http://www.ncbi.nlm.nih.gov/pubmed/10560244", "http://www.ncbi.nlm.nih.gov/pubmed/9302275", "http://www.ncbi.nlm.nih.gov/pubmed/9272155", "http://www.ncbi.nlm.nih.gov/pubmed/8180509" ], "ideal_answer": [ "The Romano Ward long QT syndrome (LQTS) has an autosomal dominant mode of inheritance." ], "exact_answer": [ "autosomal dominant" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008133", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029597", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582" ], "type": "factoid", "id": "52ee9f55c8da898910000009", "snippets": [ { "offsetInBeginSection": 301, "offsetInEndSection": 550, "text": "KCNQ1 is associated with two different entities of LQTS, the autosomal-dominant Romano-Ward syndrome (RWS), and the autosomal-recessive Jervell and Lange-Nielsen syndrome (JLNS) characterized by bilateral deafness in addition to cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The Romano Ward long QT syndrome (LQTS) has an autosomal dominant mode of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9272155", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 875, "text": "The genetic forms of LQTS include Romano-Ward syndrome (RWS), which is characterized by isolated LQTS and an autosomal dominant pattern of inheritance, and syndromes with LQTS in association with other conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19862833", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 449, "text": "The Jervell and Lange-Nielsen syndrome (JLNS) is characterized by prolongation of the QT interval, deafness, and autosomal-recessive inheritance, and the Romano-Ward syndrome is characterized by a prolonged QT interval, autosomal-dominant inheritance, and no deafness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10593671", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 612, "text": "Different mutations in KVLQT1 cause the dominant Romano-Ward (RW) syndrome and the recessive Jervell and Lange-Nielsen (JLN) syndrome, which, in addition to cardiac abnormalities, includes congenital deafness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9302275", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 450, "text": "The Romano-Ward syndrome shows an autosomal dominant pattern of inheritance and normal hearing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8223759", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 295, "text": "The Romano-Ward syndrome is of autosomal dominant inheritance, and the Jervell and Lange-Nielson syndrome, with associated deafness, of autosomal recessive inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8048706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Romano-Ward syndrome is a subtype of prolonged QT syndrome with autosomal dominant inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8098062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "A family with the Romano-Ward syndrome is presented. This family showed typical features of this syndrome with QT prolongation, torsades de pointes ventricular tachycardia, sudden death and an autosomal dominant inheritance pattern. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2771275", "endSection": "abstract" } ] }, { "body": "Which histone modifications have been associated to alternative splicing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21289049", "http://www.ncbi.nlm.nih.gov/pubmed/20407423", "http://www.ncbi.nlm.nih.gov/pubmed/19687145", "http://www.ncbi.nlm.nih.gov/pubmed/19182803", "http://www.ncbi.nlm.nih.gov/pubmed/20133523", "http://www.ncbi.nlm.nih.gov/pubmed/22242188", "http://www.ncbi.nlm.nih.gov/pubmed/21358630", "http://www.ncbi.nlm.nih.gov/pubmed/22455468", "http://www.ncbi.nlm.nih.gov/pubmed/21057525", "http://www.ncbi.nlm.nih.gov/pubmed/21173847", "http://www.ncbi.nlm.nih.gov/pubmed/22345622", "http://www.ncbi.nlm.nih.gov/pubmed/23353998" ], "ideal_answer": [ "H3K36m3 has been systematically associated to exon inclusion in almost all published studies. Other marks have been associated as well in specific studies to exon expression, but it can not be concluded that the effect of these marks in exon expression it is not a consequence of their effect in gene expression." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398" ], "type": "summary", "id": "5173b5ea8ed59a060a00001f", "snippets": [ { "offsetInBeginSection": 382, "offsetInEndSection": 706, "text": "We found that several types of histone modifications including H3K36me3 were associated with the inclusion or exclusion of alternative exons. Furthermore, we observed that the levels of H3K36me3 and H3K79me1 in the cell lines were well correlated with the differences in alternative splicing patterns between the cell lines.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23353998", "endSection": "sections.0" }, { "offsetInBeginSection": 175, "offsetInEndSection": 337, "text": "Here we find that elevated levels of trimethylation of histone H3 on Lys9 (H3K9me3) are a characteristic of the alternative exons of several genes including CD44.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358630", "endSection": "sections.0" }, { "offsetInBeginSection": 724, "offsetInEndSection": 955, "text": "he first report shows that a physiological stimulus such as neuron depolarization promotes intragenic histone acetylation (H3K9ac) and chromatin relaxation, causing the skipping of exon 18 of the neural cell adhesion molecule gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21289049", "endSection": "sections.0" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1393, "text": "Using small interfering RNAs (siRNAs), we increased the levels of H3K9me2 and H3K27me3 in the proximity of alternative exon 33 of the human fibronectin gene, favoring its inclusion into mature messenger RNA (mRNA) through a mechanism that recalls RNA-mediated transcriptional gene silencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21289049", "endSection": "sections.0" }, { "offsetInBeginSection": 646, "offsetInEndSection": 881, "text": "Among the 38 histone modifications analyzed in man, H3K36me3, H3K79me1, H2BK5me1, H3K27me1, H3K27me2, and H3K27me3 had evidently higher signals in internal exons than in the following introns and were clearly related to exon expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19687145", "endSection": "sections.0" } ] }, { "body": "Is phospholamban phosphorylated by Protein kinase A?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14577598", "http://www.ncbi.nlm.nih.gov/pubmed/12962492", "http://www.ncbi.nlm.nih.gov/pubmed/15909986", "http://www.ncbi.nlm.nih.gov/pubmed/11502581", "http://www.ncbi.nlm.nih.gov/pubmed/7857766", "http://www.ncbi.nlm.nih.gov/pubmed/19191503", "http://www.ncbi.nlm.nih.gov/pubmed/17548345", "http://www.ncbi.nlm.nih.gov/pubmed/15524173", "http://www.ncbi.nlm.nih.gov/pubmed/10330247", "http://www.ncbi.nlm.nih.gov/pubmed/15049694", "http://www.ncbi.nlm.nih.gov/pubmed/11812163", "http://www.ncbi.nlm.nih.gov/pubmed/3730367", "http://www.ncbi.nlm.nih.gov/pubmed/15362510", "http://www.ncbi.nlm.nih.gov/pubmed/15229104", "http://www.ncbi.nlm.nih.gov/pubmed/3957897", "http://www.ncbi.nlm.nih.gov/pubmed/16600289", "http://www.ncbi.nlm.nih.gov/pubmed/16226237" ], "ideal_answer": [ "Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that is phosphorylated at Ser16 by PKA. Phosphorylation of PLB by PKA reverses the inhibitory action of PLB." ], "exact_answer": "yes", "type": "yesno", "id": "54da0c524b1fd0d33c00000b", "snippets": [ { "offsetInBeginSection": 456, "offsetInEndSection": 514, "text": "cAMP-dependent protein kinase (PKA) phosphorylation of PLB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19191503", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 246, "text": "phosphorylation of PLN, at either Ser(16) by PKA ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16226237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Activation of cardiac muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) by beta1-agonists involves cAMP- and PKA-dependent phosphorylation of phospholamban (PLB), which relieves the inhibitory effects of PLB on SERCA2a. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15909986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that when phosphorylated at Ser16 by PKA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15524173", "endSection": "abstract" }, { "offsetInBeginSection": 1044, "offsetInEndSection": 1163, "text": "phosphorylation of PLB by the Ca2+-calmodulin-dependent protein kinase (CaMK) and cAMP-dependent protein kinase (PKA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15362510", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 990, "text": "cAMP-dependent protein kinase (PKA)-mediated phospholamban (PLB) phosphorylation at serine-16", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15229104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, functioning to modulate contractile force by altering the rate of calcium re-sequestration by the Ca-ATPase. Functionally, inhibition by PLB binding is manifested by shifts in the calcium dependence of Ca-ATPase activation toward higher calcium levels; phosphorylation of PLB by PKA reverses the inhibitory action of PLB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15049694", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 213, "text": "phosphorylation of both PLB residues (Ser16, PKA site, and Thr17, CaMKII site) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14577598", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1434, "text": "Phosphorylation of Ser(16) by PKA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12962492", "endSection": "abstract" }, { "offsetInBeginSection": 2296, "offsetInEndSection": 2370, "text": "stabilization of the structure of PLB following phosphorylation of Ser(16)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12962492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and this inhibition is relieved by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11502581", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1341, "text": "Two-dimensional tryptic peptide maps of phosphorylated phospholamban indicated that cAMP-dependent protein kinase phosphorylates at a single site, A, and Ca2+-calmodulin-dependent protein kinase phosphorylates at sites C1 and C2 in the low molecular weight form, where A is different from C1 but may be the same as C2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3957897", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 455, "text": "Because SR function is regulated by phosphorylation of phospholamban (PLB), a SR protein phosphorylated by cAMP-dependent protein kinase (PKA) at Ser(16)and Ca(2+)-calmodulin-dependent protein kinase (CaMKII) at Thr(17), the phosphorylation of these residues during ischemia and reperfusion was examined in Langendorff-perfused rat hearts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11812163", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 908, "text": "These changes were associated with reduced protein expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and protein kinase A phosphorylated phospholamban (PLB), which was reduced in HF, but essentially abolished in VD-HF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16600289", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1499, "text": "The data indicate that 1) phosphorylation of phospholamban at Ser16 by cAMP-dependent protein kinase is the main regulator of beta-adrenergic-induced cardiac relaxation definitely preceding Thr17 phosphorylation and 2) the beta-adrenergic-mediated phosphorylation of Thr17 by Ca2+-calmodulin-dependent protein kinase required influx of Ca2+ through the L-type Ca2+ channel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10330247", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 654, "text": "Here we extend this model to explain the reversal of SERCA2a inhibition that occurs after phosphorylation of PLB at Ser(16) by protein kinase A (PKA) and after binding of the anti-PLB monoclonal antibody 2D12, which recognizes residues 7-13 of PLB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17548345", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 421, "text": "Phospholamban is phosphorylated in heart by cAMP-dependent protein kinase, cGMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II (CM-kinase-II) and in smooth muscle cells by cGMP-dependent protein kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7857766", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Phospholamban, the cardiac sarcoplasmic reticulum proteolipid, is phosphorylated by cAMP-dependent protein kinase, by Ca2+/phospholipid-dependent protein kinase, and by an endogenous Ca2+/calmodulin-dependent protein kinase, the identity of which remains to be defined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3730367", "endSection": "abstract" } ] }, { "body": "Are there telemedicine applications for chronic pain management?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22662734", "http://www.ncbi.nlm.nih.gov/pubmed/21375412", "http://www.ncbi.nlm.nih.gov/pubmed/23291270", "http://www.ncbi.nlm.nih.gov/pubmed/23659470", "http://www.ncbi.nlm.nih.gov/pubmed/22303839", "http://www.ncbi.nlm.nih.gov/pubmed/16691087", "http://www.ncbi.nlm.nih.gov/pubmed/17336868" ], "ideal_answer": [ "Yes, telemedicine is feasible and cost-effective for education and therapy of patients with chronic pain.", "Yes, there are." ], "exact_answer": "yes", "type": "yesno", "id": "54ff106b6ad7dcbc1200000c", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 366, "text": "An integrated cognitive-behavioral and physical therapy group protocol has been developed and then implemented at remote sites using videoconferencing technology to provide pain management for veterans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22662734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Tele-pain management: use of videoconferencing technology in the delivery of an integrated cognitive-behavioral and physical therapy group intervention.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22662734", "endSection": "title" }, { "offsetInBeginSection": 1517, "offsetInEndSection": 1720, "text": "It is feasible to provide treatment to women veterans living in rural areas by utilizing video-teleconferencing technology between larger VA medical centers and facilities at CBOCs in more rural settings", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659470", "endSection": "abstract" }, { "offsetInBeginSection": 2204, "offsetInEndSection": 2470, "text": "The results suggest that a smartphone-delivered intervention with diaries and personalized feedback can reduce catastrophizing and prevent increases in functional impairment and symptom levels in women with chronic widespread pain following inpatient rehabilitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23291270", "endSection": "abstract" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1426, "text": " Of the studies available, there are very few randomized trials of telehealth pain care and only one general overview of e-health and chronic pain, which dedicates just a few paragraphs to telehealth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22303839", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 405, "text": "therapy adaptation and the resultant specification for the SMART2 project-a technology-based self-management system for assisting long-term health conditions, including chronic pain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21375412", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1278, "text": "Results showed the use of videoconferencing for this group of patients is useable and satisfactory for both patients and staff, that the patients save time and money, and that for a system where videoconferencing equipment is already in use, it is also cost effective. Staff were able to identify new patient problems. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17336868", "endSection": "abstract" }, { "offsetInBeginSection": 1557, "offsetInEndSection": 1766, "text": "This pilot study indicates that telemedicine follow-up consultations for chronic pain patients are feasible and cost-saving. Patients and anesthesiologists were highly satisfied with telemedicine consultation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16691087", "endSection": "abstract" } ] }, { "body": "What is a P-body (processing body)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25529221", "http://www.ncbi.nlm.nih.gov/pubmed/25482014", "http://www.ncbi.nlm.nih.gov/pubmed/24862735", "http://www.ncbi.nlm.nih.gov/pubmed/25514416", "http://www.ncbi.nlm.nih.gov/pubmed/24755989", "http://www.ncbi.nlm.nih.gov/pubmed/25416063", "http://www.ncbi.nlm.nih.gov/pubmed/25339350", "http://www.ncbi.nlm.nih.gov/pubmed/25110026", "http://www.ncbi.nlm.nih.gov/pubmed/24659297", "http://www.ncbi.nlm.nih.gov/pubmed/25110034", "http://www.ncbi.nlm.nih.gov/pubmed/24569876", "http://www.ncbi.nlm.nih.gov/pubmed/24860588", "http://www.ncbi.nlm.nih.gov/pubmed/24418890", "http://www.ncbi.nlm.nih.gov/pubmed/25128566", "http://www.ncbi.nlm.nih.gov/pubmed/25437551", "http://www.ncbi.nlm.nih.gov/pubmed/24292556", "http://www.ncbi.nlm.nih.gov/pubmed/24525673", "http://www.ncbi.nlm.nih.gov/pubmed/24918601", "http://www.ncbi.nlm.nih.gov/pubmed/24504254" ], "ideal_answer": [ "Processing bodies (P bodies, PB) are cytoplasmic protein complexes involved in degradation and translational arrest of mRNA." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043186", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000932", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033962", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010494" ], "type": "summary", "id": "54d8e59f4b1fd0d33c000001", "snippets": [ { "offsetInBeginSection": 803, "offsetInEndSection": 855, "text": " processing (P) bodies, a site for mRNA degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514416", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 400, "text": "processing bodies are RNA-containing granules that contribute to this process by modulating cellular signaling pathways, metabolic machinery, and stress response programs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25482014", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 304, "text": "translationally repressed mRNAs localize to P-bodies and stress granules where their decay and storage, respectively, are directed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437551", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 479, "text": "stress-dependent formation of P-bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437551", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1122, "text": " P-bodies involved in RNA metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25416063", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 288, "text": "cytoplasmic RNA granules called processing bodies (P-bodies)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25339350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The 5'-to-3' mRNA degradation machinery localizes to cytoplasmic processing bodies (P-bodies), which are non-membranous structures found in all eukaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25128566", "endSection": "abstract" }, { "offsetInBeginSection": 1044, "offsetInEndSection": 1166, "text": "This analysis demonstrates the dual role of P-bodies as decay sites and storage areas under regular and stress conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25128566", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 396, "text": " mRNA P-bodies (processing bodies) harbour much of the mRNA decay machinery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25110034", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 256, "text": "P-bodies contain the mRNA decay and translational repression machineries ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25110026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "P-bodies belong to a large family of RNA granules that are associated with post-transcriptional gene regulation, conserved from yeast to mammals, and influence biological processes ranging from germ cell development to neuronal plasticity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24918601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "In eukaryotic cells, components of the 5' to 3' mRNA degradation machinery can undergo a rapid phase transition. The resulting cytoplasmic foci are referred to as processing bodies (P-bodies). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24862735", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 402, "text": "Processing bodies (P bodies, PB) are cytoplasmic protein complexes involved in degradation and translational arrest of mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24860588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The mRNA processing body (P-body) is a cellular structure that regulates the stability of cytoplasmic mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24755989", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 215, "text": "while most other messenger RNAs (mRNAs) are stored away in stress granules or degraded in processing bodies (P-bodies).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24659297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Numerous mRNAs are degraded in processing bodies (P bodies) in Saccharomyces cerevisiae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24569876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Processing (P)-bodies are cytoplasmic RNA protein aggregates responsible for the storage, degradation, and quality control of translationally repressed messenger RNAs in eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24525673", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 916, "text": "in P-bodies (PBs), where translationally silenced mRNAs are deposited, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Processing bodies (P-bodies) are cytoplasmatic mRNP granules containing non-translating mRNAs and proteins from the mRNA decay and silencing machineries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24418890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The control of mRNA translation and degradation is mediated in part by a set of proteins that can inhibit translation and promote decapping, as well as function in the assembly of cytoplasmic mRNP granules referred to as processing bodies (P-bodies). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24504254", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of decitabine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25130173", "http://www.ncbi.nlm.nih.gov/pubmed/25123082", "http://www.ncbi.nlm.nih.gov/pubmed/16043219", "http://www.ncbi.nlm.nih.gov/pubmed/24286424", "http://www.ncbi.nlm.nih.gov/pubmed/16273408", "http://www.ncbi.nlm.nih.gov/pubmed/16585166", "http://www.ncbi.nlm.nih.gov/pubmed/22893792", "http://www.ncbi.nlm.nih.gov/pubmed/16211386" ], "ideal_answer": [ "Decitabine reactivates unmethylated p21WAF1 in some AML cell lines but the possible occurrence of p21WAF1 methylation in AML in vivo has not been studied in detail and decitabine effects on p21WAF1 chromatin remodeling have not been reported. We also discuss the following questions: What is the best administration schedule of decitabine in solid tumors? Is there tumor type specificity for decitabine-based epigenetic therapy? We found that p21WAF1 mRNA was undetectable in 6 of 24 AML patient samples and 4 of 5 AML cell lines but there was no evidence of p21WAF1 promoter methylation.", "The use of the DNA methylation inhibitor decitabine (Dacogen\u00ae) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention.", "Decitabine is a potent demethylating agent that exhibits clinical activity against myeloid malignancies. Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones. Recent studies indicating that decitabine also induces regional chromatin remodeling of some unmethylated genes suggest additional mechanisms of action." ], "concepts": [ "http://www.biosemantics.org/jochem#4269908", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4269908" ], "type": "summary", "id": "57169a49cb4ef8864c00000a", "snippets": [ { "offsetInBeginSection": 92, "offsetInEndSection": 284, "text": "The use of the DNA methylation inhibitor decitabine (Dacogen\u00ae) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25130173", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 913, "text": "low-dose decitabine and combined therapy show significant improvement in solid tumor treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25130173", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 405, "text": "Here, we demonstrate dose-dependent degradation of Dnmt1 in mouse embryonic stem (ES) cells expressing catalytic site mutant (cys-ser), confirming that the covalent bond formation between Dnmt1 and decitabine-incorporated DNA is not essential for this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893792", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 633, "text": "NMT1o, the oocyte-specific isoform that lacks the N-terminal 118-amino acid domain, did not undergo decitabine-mediated degradation, which further proves the requirement of multiple domains including nuclear localization signa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893792", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 859, "text": "Analysis of glycerol density gradient fractions of micrococcal nuclease-digested nuclei showed that both nucleosomal and nucleoplasmic DNMT1 are degraded upon decitabine treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893792", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1161, "text": "The maximal effect caused by inhibiting protein kinase C (PKC) persuaded us to investigate further its role in decitabine-mediated DNMT1 degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893792", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1766, "text": "These studies provide substantial evidence that decitabine-induced degradation of the maintenance methyltransferase DNMT1 does not require covalent bond formation with the substrate and also elucidate its underlying molecular mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 481, "text": "Decitabine is a potent demethylating agent that exhibits clinical activity against myeloid malignancies. Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones. Recent studies indicating that decitabine also induces regional chromatin remodeling of some unmethylated genes suggest additional mechanisms of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16043219", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1538, "text": "Our findings indicate that decitabine can relieve p21WAF1 repression in AML by a mechanism that involves release of HDAC1 without requiring promoter demethylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16043219", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 550, "text": "Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16043219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "5-Aza-2'-deoxycytidine (decitabine) can relieve p21WAF1 repression in human acute myeloid leukemia by a mechanism involving release of histone deacetylase 1 (HDAC1) without requiring p21WAF1 promoter demethylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16043219", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic syndromes and gains better overall survival, which is based on epigenetic mechanism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25123082", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 241, "text": "Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism, thus enhance the immunogenicity of leukemia cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24286424", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1080, "text": "However, further elucidation of its mechanism of action is required, as clinical response to decitabine does not correlate with demethylation of the p15 gene promoter or the repetitive DNA element LINE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16273408", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 402, "text": "In the area of epigenetic therapy, the demethylating drug decitabine (5-aza-2'-deoxycytidine) is increasingly used to treat acute myelogenous leukemia and myelodysplastic syndrome, but the mechanisms of its anticancer activity have remained unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16585166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2'-deoxycytidine (decitabine) in 177 patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16211386", "endSection": "title" }, { "offsetInBeginSection": 106, "offsetInEndSection": 482, "text": "Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones. Recent studies indicating that decitabine also induces regional chromatin remodeling of some unmethylated genes suggest additional mechanisms of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16043219", "endSection": "abstract" }, { "offsetInBeginSection": 878, "offsetInEndSection": 1080, "text": "However, further elucidation of its mechanism of action is required, as clinical response to decitabine does not correlate with demethylation of the p15 gene promoter or the repetitive DNA element LINE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16273408", "endSection": "abstract" } ] }, { "body": "Which gene is associated with the Mitchell-Riley syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21215266", "http://www.ncbi.nlm.nih.gov/pubmed/23914949" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17467973", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2748662", "o": "http://linkedlifedata.com/resource/umls/label/A17467973" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17467973", "o": "MITCHELL-RILEY SYNDROME" } ], "ideal_answer": [ "Mutations in the gene coding for the transcription factor RFX6 (regulatory factor X,6) have been described as the cause of the Mitchell-Riley syndrome." ], "exact_answer": [ "RFX6" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004402", "http://www.disease-ontology.org/api/metadata/DOID:0050657", "http://www.disease-ontology.org/api/metadata/DOID:11589", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "factoid", "id": "52e92c6e98d0239505000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Mutations in rfx6 were recently associated with Mitchell-Riley syndrome, which involves neonatal diabetes, and other digestive system defects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21215266", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 215, "text": "bi-allelic mutations in the transcription factor RFX6 were described as the cause of a rare condition characterized by neonatal diabetes with pancreatic and biliary hypoplasia and duodenal/jejunal atresia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23914949", "endSection": "abstract" } ] }, { "body": "Is paramyxovirus involved in human subacute thyroiditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22819125", "http://www.ncbi.nlm.nih.gov/pubmed/1691523", "http://www.ncbi.nlm.nih.gov/pubmed/806773", "http://www.ncbi.nlm.nih.gov/pubmed/20960165", "http://www.ncbi.nlm.nih.gov/pubmed/9797", "http://www.ncbi.nlm.nih.gov/pubmed/22459018", "http://www.ncbi.nlm.nih.gov/pubmed/2998895", "http://www.ncbi.nlm.nih.gov/pubmed/1180050", "http://www.ncbi.nlm.nih.gov/pubmed/20886354", "http://www.ncbi.nlm.nih.gov/pubmed/9637274", "http://www.ncbi.nlm.nih.gov/pubmed/16279854" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7165", "o": "Granulomatous thyroiditis" } ], "ideal_answer": [ "There is no evidence that paramyxovirus are involved in etiology of subacute thyroiditis." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013968", "http://www.disease-ontology.org/api/metadata/DOID:7165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018109", "http://www.disease-ontology.org/api/metadata/DOID:7187", "http://www.disease-ontology.org/api/metadata/DOID:7166" ], "type": "yesno", "id": "513efe01bee46bd34c00000e", "snippets": [ { "offsetInBeginSection": 95, "offsetInEndSection": 310, "text": "Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus. Influenza immunization or infection may cause subacute thyroiditis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819125", "endSection": "sections.0" }, { "offsetInBeginSection": 396, "offsetInEndSection": 483, "text": "Coxsackie virus has been reported to be one of the viruses associated with the disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20886354", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it is postulated to be associated with viral infections and genetic factors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9637274", "endSection": "sections.0" }, { "offsetInBeginSection": 1511, "offsetInEndSection": 1587, "text": "The results suggest that SAT is not usually associated with acute infections", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9637274", "endSection": "sections.0" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1699, "text": "No evidence was obtained to support the proposed role of enteroviruses as an important etiologic agent of SAT.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9637274", "endSection": "sections.0" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1400, "text": "The viral antibodies evaluated were those of Influenza A and B, Coxsackie A9, B1, B2, B3, B4, B5 and B6, Echo 3, 7, 11 and 12, Parainfluenza 1, 2, 3 and 4, and Adeno 8 virus. The following results were obtained: In class I HLA typing, the frequency of HLA-Bw35 in SAT was 67.4%, which was significantly (p less than 0.0001) higher than that in the control (14.1%). On the other hand, the frequency of Cw1 in SAT (14.6%) was significantly (p less than 0.01) lower than that of the control (32.1%), and that of Cw3 (65.2%) was significantly (p less than 0.01) higher than that of the control (46.5%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2998895", "endSection": "sections.0" } ] }, { "body": "What are the mobile applications fields of use for patients ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22942063", "http://www.ncbi.nlm.nih.gov/pubmed/24073184", "http://www.ncbi.nlm.nih.gov/pubmed/24067948", "http://www.ncbi.nlm.nih.gov/pubmed/24139770", "http://www.ncbi.nlm.nih.gov/pubmed/21689119", "http://www.ncbi.nlm.nih.gov/pubmed/21591562", "http://www.ncbi.nlm.nih.gov/pubmed/23821609" ], "ideal_answer": [ "Weight-loss mobile applications\npediatric obesity prevention and treatment, healthy eating, and physical activity promotion\nA total of 229 dermatology-related apps were identified in the following categories: general dermatology reference (61 [26.6%]), self-surveillance/diagnosis (41 [17.9%]), disease guide (39 [17.0%]), educational aid (20 [8.7%]), sunscreen/UV recommendation (19 [8.3%]), calculator (12 [5.2%]), teledermatology (8 [3.5%]), conference (6 [2.6%]), journal (6 [2.6%]), photograph storage/sharing (5 [2.2%]), dermoscopy (2 [0.9%]), pathology (2 [0.9%]), and other (8 [3.5%]). The most reviewed apps included Ultraviolet\u2009~\u2009UV Index (355 reviews), VisualDx (306), SPF (128), iSore (61), and SpotMole (50)\nmobile health and fitness app\nalcohol-use behavior change or recovery\nMore than 17,000 mHealth apps now are available for smart phones and other devices, and they do everything from monitoring urine flow for patients with enlarged prostates to reminding people prone to kidney stones to drink more water." ], "exact_answer": [ [ "weight loss" ], [ "exercise", "physical activity", "fitness" ], [ "dermatology" ], [ "alcohol-use behavior change" ], [ "urine flow" ], [ "fluid intake" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063731", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017216" ], "type": "list", "id": "5324cca79b2d7acc7e00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Evidence-based strategies in weight-loss mobile apps", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24139770", "endSection": "title" }, { "offsetInBeginSection": 168, "offsetInEndSection": 246, "text": "Weight-loss mobile applications (apps) have the potential to be a helpful tool", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24139770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Mobile apps for pediatric obesity prevention and treatment, healthy eating, and physical activity promotion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24073184", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Mobile applications (apps) offer a novel way to engage children in behavior change,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24073184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "Mobile applications in dermatology", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24067948", "endSection": "title" }, { "offsetInBeginSection": 782, "offsetInEndSection": 1379, "text": "A total of 229 dermatology-related apps were identified in the following categories: general dermatology reference (61 [26.6%]), self-surveillance/diagnosis (41 [17.9%]), disease guide (39 [17.0%]), educational aid (20 [8.7%]), sunscreen/UV recommendation (19 [8.3%]), calculator (12 [5.2%]), teledermatology (8 [3.5%]), conference (6 [2.6%]), journal (6 [2.6%]), photograph storage/sharing (5 [2.2%]), dermoscopy (2 [0.9%]), pathology (2 [0.9%]), and other (8 [3.5%]). The most reviewed apps included Ultraviolet\u2009~\u2009UV Index (355 reviews), VisualDx (306), SPF (128), iSore (61), and SpotMole (50).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24067948", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1644, "text": " Twenty-seven mobile apps were identified and reviewed that involved general pharmacy practice, including apps that involved drug references, clinical references, medical calculators, laboratory references, news and continuing medical education, and productivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821609", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 304, "text": "Today, many high quality mobile apps are available for users and health professionals and cover the whole health care chain, i.e. information collection, prevention, diagnosis, treatment and monitoring", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22942063", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 388, "text": "Our team has developed a mobile health and fitness app called myFitnessCompanion\u00ae ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22942063", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 688, "text": "to examine the current available mobile smartphone applications (e.g., apps) that utilize principles of ecological momentary assessment (EMA)-daily self-monitoring or near real-time self-assessment of alcohol-use behavior-to promote positive behavior change, alcohol harm reduction, psycho-education about alcohol use, or abstinence from alcohol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21689119", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1190, "text": "few apps addressed alcohol-use behavior change or recovery. Aside from tracking drinking consumption, a minority utilized empirically based components of alcohol treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21689119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "More than 17,000 mHealth apps now are available for smart phones and other devices, and they do everything from monitoring urine flow for patients with enlarged prostates to reminding people prone to kidney stones to drink more water.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21591562", "endSection": "abstract" } ] }, { "body": "Is there any link between the aurora B kinase and the polycomb protein ring1B?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24034696" ], "ideal_answer": [ "Yes. The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064127", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064107", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063146", "http://www.biosemantics.org/jochem#4262561" ], "type": "yesno", "id": "56ae67a40a360a5e4500000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24034696", "endSection": "title" }, { "offsetInBeginSection": 172, "offsetInEndSection": 974, "text": "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T\u00a0cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. Aurora B phosphorylates histone H3S28 at active promoters in resting B cells as well as inhibiting Ring1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Our results identify a mechanism for regulating transcription in quiescent cells that has implications for epigenetic regulation of the choice between proliferation and quiescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24034696", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 483, "text": "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24034696", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 564, "text": "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T\u00a0cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24034696", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 416, "text": "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T\u00a0cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24034696", "endSection": "abstract" } ] }, { "body": "Which are the genes responsible for Dyskeratosis Congenita?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10903840", "http://www.ncbi.nlm.nih.gov/pubmed/22160078", "http://www.ncbi.nlm.nih.gov/pubmed/21199492", "http://www.ncbi.nlm.nih.gov/pubmed/20301779", "http://www.ncbi.nlm.nih.gov/pubmed/18989882", "http://www.ncbi.nlm.nih.gov/pubmed/15842668", "http://www.ncbi.nlm.nih.gov/pubmed/20687509", "http://www.ncbi.nlm.nih.gov/pubmed/9886310", "http://www.ncbi.nlm.nih.gov/pubmed/15304085", "http://www.ncbi.nlm.nih.gov/pubmed/9863595", "http://www.ncbi.nlm.nih.gov/pubmed/19419704" ], "ideal_answer": [ "To date, 8 genes have been associated with Dyskeratosis Congenita development. These are DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1. Seven of these are important in telomere maintenance, because either they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2).", "To date, CTC1, DKC1, TERC, TERT, TINF2, NHP2, NOP10, and WRAP53 are the genes in which mutations are known to cause DC and result in very short telomeres Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2) " ], "exact_answer": [ [ "DKC1" ], [ "TERC" ], [ "TERT" ], [ "NOP10" ], [ "NHP2" ], [ "TIN2" ], [ "C16orf57" ], [ "TCAB1" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2729" ], "type": "list", "id": "54f431d664850a5854000006", "snippets": [ { "offsetInBeginSection": 293, "offsetInEndSection": 458, "text": "Studies over the last 15 years have led to significant advances, with 8 DC genes (DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1) having been characterized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22160078", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 659, "text": "Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22160078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Dyskeratosis congenita (DC) is a heterogeneous bone marrow failure syndrome with seven disease-causing genes identified to date, six of which are linked to telomere maintenance. Mutations in one of these genes (TINF2), which encodes a component of the shelterin complex, are associated with particularly short telomeres", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Dyskeratosis congenita (DC) is an inheritable bone marrow failure syndrome characterized by reticulated hyperpigmentation, dystrophic nails and oral leukoplakia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20687509", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 742, "text": "Four genes, namely DKC1 (codes for dyskerin), TERC and TERT (code for telomerase) and NOP10, have been implicated in the pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20687509", "endSection": "abstract" }, { "offsetInBeginSection": 1619, "offsetInEndSection": 1772, "text": "To date, CTC1, DKC1, TERC, TERT, TINF2, NHP2, NOP10, and WRAP53 are the genes in which mutations are known to cause DC and result in very short telomeres", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301779", "endSection": "abstract" }, { "offsetInBeginSection": 3731, "offsetInEndSection": 3932, "text": "The mode of inheritance of DC varies by gene: DKC1 (X-linked), TERC and TINF2 (autosomal dominant), TERT (autosomal dominant or autosomal recessive), CTC1, WRAP53, NHP2, and NOP10 (autosomal recessive)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301779", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 990, "text": "Six genes have been identified, defects in which cause different genetic subtypes (X-linked recessive, autosomal dominant, autosomal recessive) of DC. The products of these genes encode components that are critical for telomere maintenance; either because they are core constituents of telomerase (dyskerin, TERC, TERT, NOP10 and NHP2) or are part of the shelterin complex that protects the telomeric end (TIN2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19419704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND: Telomerase complex genes mutations (DKC1, TERC, TERT, and NOP10) lead to premature telomere shortening and are responsible for different forms of dyskeratosis congenita.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989882", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 329, "text": "Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15304085", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 371, "text": "The DC1 gene responsible for the X linked form (MIM 305000) of dyskeratosis congenita has been mapped to Xq28.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9863595", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 370, "text": "The DC1 gene responsible for the X linked form (MIM 305000) of dyskeratosis congenita has been mapped to Xq28", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9863595", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 328, "text": "Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15304085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Mutations in the DKC1 gene are responsible for causing X-linked recessive dyskeratosis congenita (DKC) and a more severe allelic variant of the disease, Hoyeraal-Hreidarsson syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10903840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Telomerase complex genes mutations (DKC1, TERC, TERT, and NOP10) lead to premature telomere shortening and are responsible for different forms of dyskeratosis congenita", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989882", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1145, "text": "Linkage analysis in multiplex families confirmed that the DKC1 gene, responsible for the X-linked form of DC, is located within Xq28 and facilitated its positional cloning", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886310", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 379, "text": "DKC1 has been identified as the gene responsible for X-linked DC, and genetic analyses have been performed in a worldwide study", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15842668", "endSection": "abstract" } ] }, { "body": "Is CD99 encoded by MIC2 gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25007147", "http://www.ncbi.nlm.nih.gov/pubmed/8399135", "http://www.ncbi.nlm.nih.gov/pubmed/24322504", "http://www.ncbi.nlm.nih.gov/pubmed/17725386", "http://www.ncbi.nlm.nih.gov/pubmed/10941840", "http://www.ncbi.nlm.nih.gov/pubmed/9623916", "http://www.ncbi.nlm.nih.gov/pubmed/10492040", "http://www.ncbi.nlm.nih.gov/pubmed/24158076", "http://www.ncbi.nlm.nih.gov/pubmed/1867320", "http://www.ncbi.nlm.nih.gov/pubmed/15359120", "http://www.ncbi.nlm.nih.gov/pubmed/10782405", "http://www.ncbi.nlm.nih.gov/pubmed/11037347", "http://www.ncbi.nlm.nih.gov/pubmed/15978751", "http://www.ncbi.nlm.nih.gov/pubmed/9278313", "http://www.ncbi.nlm.nih.gov/pubmed/22356523", "http://www.ncbi.nlm.nih.gov/pubmed/23644663", "http://www.ncbi.nlm.nih.gov/pubmed/21063743", "http://www.ncbi.nlm.nih.gov/pubmed/22020966", "http://www.ncbi.nlm.nih.gov/pubmed/10688843" ], "ideal_answer": [ "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene ", "CD99 is a transmembrane protein encoded by MIC2 gene. It is involved in multiple cellular functions, including cell adhesion and migration, apoptosis, cell differentiation, and regulation of protein trafficking, in either physiological or pathological conditions." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/CD99_HUMAN" ], "type": "yesno", "id": "55376b37bc4f83e82800000b", "snippets": [ { "offsetInBeginSection": 285, "offsetInEndSection": 488, "text": "We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24322504", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 609, "text": "We obtained the final diagnosis of ES/PNET by immunohistochemical molecular study with positive staining for the MIC2 gene product (CD99) and a Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24158076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23644663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020966", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 445, "text": "The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21063743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17725386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15359120", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 374, "text": "Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15978751", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 697, "text": "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10782405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23644663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism coregulated with the polymorphism of the XG blood group gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10688843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10941840", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1183, "text": "Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9623916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11037347", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 615, "text": "MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22356523", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 376, "text": "Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15978751", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 699, "text": "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10782405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9278313", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Relation of neurological marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10492040", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The Ewing family of tumors (EFT) is characterized by high MIC2/CD99 expression and specific EWS/ETS gene rearrangements, resulting in different chimeric transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10492040", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 701, "text": "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10782405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1867320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Monoclonal antibodies (mAbs) directed against E2, a 32-kDa transmembrane protein encoded by the MIC2 gene located in the pseudoautosomal region, induce a transbilayer movement of phosphatidylserine and, to a lesser extent, phosphatidylethanolamine in human thymocytes and a Jurkat T lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8399135", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1188, "text": "Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9623916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23644663", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 444, "text": "The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21063743", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 487, "text": "We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24322504", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 617, "text": "MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22356523", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1034, "text": "Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25007147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15359120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17725386", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 700, "text": "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10782405", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 375, "text": "Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15978751", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 618, "text": "MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22356523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10941840", "endSection": "abstract" } ] }, { "body": "Name five programs for transcript quantification from RNASeq experiments", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20436464", "http://www.ncbi.nlm.nih.gov/pubmed/22285831", "http://www.ncbi.nlm.nih.gov/pubmed/21896509", "http://www.ncbi.nlm.nih.gov/pubmed/23616006", "http://www.ncbi.nlm.nih.gov/pubmed/23888185", "http://www.ncbi.nlm.nih.gov/pubmed/23821651", "http://www.ncbi.nlm.nih.gov/pubmed/23349747", "http://www.ncbi.nlm.nih.gov/pubmed/22537040", "http://www.ncbi.nlm.nih.gov/pubmed/21816040", "http://www.ncbi.nlm.nih.gov/pubmed/22072384", "http://www.ncbi.nlm.nih.gov/pubmed/24130305", "http://www.ncbi.nlm.nih.gov/pubmed/21106091", "http://www.ncbi.nlm.nih.gov/pubmed/24209455", "http://www.ncbi.nlm.nih.gov/pubmed/21794104", "http://www.ncbi.nlm.nih.gov/pubmed/21059678", "http://www.ncbi.nlm.nih.gov/pubmed/23980025", "http://www.ncbi.nlm.nih.gov/pubmed/23329413", "http://www.ncbi.nlm.nih.gov/pubmed/23155066", "http://www.ncbi.nlm.nih.gov/pubmed/23461570", "http://www.ncbi.nlm.nih.gov/pubmed/23202426", "http://www.ncbi.nlm.nih.gov/pubmed/23734627", "http://www.ncbi.nlm.nih.gov/pubmed/22592379" ], "ideal_answer": [ "Popular programs for transcript quantification from RNASeq experiments include: Cufflinks, RSEM, Flux Capacitor, Mitie, Miso, Tigar, Montebello, Drut, Traph, Pome, IsoformEx, Neuma," ], "exact_answer": [ [ "Cufflinks" ], [ "RSEM" ], [ "Flux Capacitor" ], [ "Mitie" ], [ "Miso" ], [ "Tigar" ], [ "Montebello" ], [ "Drut" ], [ "Traph" ], [ "Pome" ], [ "IsoformEx" ], [ "Neuma" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017423" ], "type": "list", "id": "5354f289288f4dae47000008", "snippets": [ { "offsetInBeginSection": 1228, "offsetInEndSection": 1257, "text": "Splicing Analysis Kit (Spanki", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24209455", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 936, "text": "ORMAN ( O ptimal R esolution of M ultimapping A mbiguity of R N A-Seq Reads), which aims to compute the minimum number of potential transcript products for each gene and to assign each multimapping read to one of these transcripts based on the estimated distribution of the region covering the read.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24130305", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 550, "text": "MITIE (Mixed Integer Transcript IdEntification) for simultaneous transcript reconstruction and quantification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23980025", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1120, "text": "Montebello, an integrated statistical approach which performs simultaneous isoform discovery and quantification by using a Monte Carlo simulation to find the most likely isoform composition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23888185", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 91, "text": "IGAR: transcript isoform abundance estimation method with gapped alignment of RNA-Seq data", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821651", "endSection": "title" }, { "offsetInBeginSection": 484, "offsetInEndSection": 565, "text": "a statistical method to estimate transcript isoform abundances from RNA-Seq data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821651", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 50, "text": "RNA-Seq data with TopHat and Cufflinks", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23616006", "endSection": "title" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1799, "text": "Experimental results on prediction accuracy show that our method is very competitive with popular tools such as Cufflinks and IsoLasso. Our tool, called Traph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23734627", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1526, "text": "By resolving the linear system with LASSO, our approach can infer an accurate set of dominantly expressed transcripts while existing methods tend to assign positive expression to every candidate isoform", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23461570", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 691, "text": "the Minimum Unique Length Tool (MULTo), a framework for efficient and comprehensive representation of mappability information, through identification of the shortest possible length required for each genomic coordinate to become unique in the genome and transcriptome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349747", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 732, "text": " a pipeline for processing and analyzing RNA-Seq data, that we have named Grape (Grape RNA-Seq Analysis Pipeline Environment)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23329413", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 653, "text": "Our method, referred as Discovery and Reconstruction of Unannotated Transcripts (DRUT), can be used to enhance existing transcriptome assemblers, such as Cufflinks, as well as to accurately estimate the transcript frequencies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23202426", "endSection": "abstract" }, { "offsetInBeginSection": 2041, "offsetInEndSection": 2051, "text": "DiffSplice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23155066", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 513, "text": "Omicsoft sequence aligner (OSA), a fast and accurate alignment tool for RNA-Seq data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22592379", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 754, "text": " two popular tools for isoform quantification, MISO and Cufflinks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22537040", "endSection": "abstract" }, { "offsetInBeginSection": 1025, "offsetInEndSection": 1130, "text": " The method is implemented in the seqbias R/Bioconductor package, available freely under the LGPL license", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22285831", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 802, "text": "Poisson mixed-effects (POME) model to characterize base-level read coverage within each transcript", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22072384", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 466, "text": "SpliceTrap, a method to quantify exon inclusion levels using paired-end RNA-seq data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896509", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 744, "text": "We present RSEM, an user-friendly software package for quantifying gene and isoform abundances from single-end or paired-end RNA-Seq data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816040", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 505, "text": "We propose a novel algorithm (IsoformEx) that employs weighted non-negative least squares estimation method to estimate the expression levels of transcript isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21794104", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 556, "text": "Rnnotator, an automated software pipeline that generates transcript models by de novo assembly of RNA-Seq data without the need for a reference genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106091", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 347, "text": "Here we introduce such algorithms in an open-source software program called Cufflinks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20436464", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 322, "text": "propose a novel, efficient and intuitive approach of estimating mRNA abundances from the whole transcriptome shotgun sequencing (RNA-Seq) data. Our method, NEUMA (Normalization by Expected Uniquely Mappable Area), is based on effective length normalization using uniquely mappable areas of gene and mRNA isoform models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21059678", "endSection": "abstract" } ] }, { "body": "What are the main characteristics/symptoms of the \"Brugada\" syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23905889", "http://www.ncbi.nlm.nih.gov/pubmed/14671564", "http://www.ncbi.nlm.nih.gov/pubmed/24827804", "http://www.ncbi.nlm.nih.gov/pubmed/23669108", "http://www.ncbi.nlm.nih.gov/pubmed/22559801", "http://www.ncbi.nlm.nih.gov/pubmed/10443304", "http://www.ncbi.nlm.nih.gov/pubmed/24405173", "http://www.ncbi.nlm.nih.gov/pubmed/11892423", "http://www.ncbi.nlm.nih.gov/pubmed/25448794", "http://www.ncbi.nlm.nih.gov/pubmed/10959460", "http://www.ncbi.nlm.nih.gov/pubmed/22451857", "http://www.ncbi.nlm.nih.gov/pubmed/24352520", "http://www.ncbi.nlm.nih.gov/pubmed/23612926", "http://www.ncbi.nlm.nih.gov/pubmed/24932359", "http://www.ncbi.nlm.nih.gov/pubmed/25187091" ], "ideal_answer": [ "In 1992, Brugada and Brugada first described a new entity, which became known as Brugada syndrome, that is associated with a high risk of ventricular arrhythmias and sudden cardiac death in patients without structural heart disease. This syndrome is characterized by a distinct electrocardiographic phenotype, type 1 Brugada pattern, consisting of a coved ST-segment elevation (\u22650.2 mV) followed by a negative T wave in more than one right precordial lead. The typical Brugada electrocardiogram (ECG) phenotype is often concealed in affected population. Brugada syndrome is a genetically determined familial disease with autosomal dominant transmission and variable penetrance, conferring a predisposition to sudden cardiac death due to ventricular arrhythmias. Brugada syndrome (BrS)is considered to be a primary inherited channelopathy often involving the inward sodium current and the diagnosis has traditionally required the exclusion of overt structural heart disease. Brugada syndrome (BrS) is an inherited cardiac disease characterized by ST segment elevation in V1-V3 ECG leads. Mutations SCN5A gene encoding for the cardiac voltage-gated Na(+) channel are found in some BrS patients, but also in family members with isolated conduction disturbances." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "summary", "id": "54d8efb84b1fd0d33c000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 456, "text": "In 1992, Brugada and Brugada first described a new entity, which became known as Brugada syndrome, that is associated with a high risk of ventricular arrhythmias and sudden cardiac death in patients without structural heart disease. This syndrome is characterized by a distinct electrocardiographic phenotype, type 1 Brugada pattern, consisting of a coved ST-segment elevation (\u22650.2 mV) followed by a negative T wave in more than one right precordial lead.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25448794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Brugada syndrome predisposes individuals to ventricular arrhythmias and sudden cardiac death, in the absence of structural heart disease. The typical Brugada electrocardiogram (ECG) phenotype is often concealed in affected population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25187091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Brugada syndrome is a rare cardiac arrhythmia characterized by electrocardiographic right bundle branch block and persistent ST-segment elevation in the right precordial leads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24932359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Brugada syndrome is a genetically determined familial disease with autosomal dominant transmission and variable penetrance, conferring a predisposition to sudden cardiac death due to ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24827804", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 44, "text": "Brugada syndrome (BrS) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24405173", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 298, "text": "BrS is considered to be a primary inherited channelopathy often involving the inward sodium current and the diagnosis has traditionally required the exclusion of overt structural heart disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24405173", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 97, "text": "Brugada syndrome (BrS) primarily associates with the loss of sodium channel function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24352520", "endSection": "abstract" }, { "offsetInBeginSection": 1778, "offsetInEndSection": 1854, "text": "PKP2 mutations may be a molecular substrate leading to the diagnosis of BrS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24352520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Brugada syndrome is an inherited arrhythmia syndrome predisposing to sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23905889", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 239, "text": "the first mutations in SCN5A encoding the cardiac sodium channel Nav1.5 were reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23905889", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 152, "text": "Brugada syndrome is characterized by typical ECG features, ventricular arrhythmias and sudden cardiac death (SCD), more frequent during nighttime.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23669108", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 290, "text": "Brugada syndrome (BrS) is an inherited cardiac disease characterized by ST segment elevation in V1-V3 ECG leads. Mutations SCN5A gene encoding for the cardiac voltage-gated Na(+) channel are found in some BrS patients, but also in family members with isolated conduction disturbances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23612926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Brugada syndrome (BrS), one of the most frequently diagnosed inherited arrhythmogenic syndromes, is responsible for more than 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22559801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Brugada syndrome is a major cause of sudden death in young adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Brugada's syndrome is one of the main causes of sudden death in young adults without a structural heart disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10959460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 545, "text": "The Brugada syndrome is a clinical-electrocardiographic diagnosis characterized by syncopal episodes or sudden death (caused by ventricular tachycardia and ventricular fibrillation) in patients with a structurally normal heart with a characteristic electrocardiographic pattern consisting of ST segment elevation in precordial leads (Vl-V3) and a morphology of the QRS complex resembling right bundle branch block (the latter can transiently disappear). Timely diagnosis and adequate treatment may essentially decrease mortality of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14671564", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 17, "text": "Brugada syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443304", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 532, "text": "In 1992 we described a new syndrome consisting of syncopal episodes and/or sudden death in patients with a structurally normal heart and a characteristic electrocardiogram displaying a pattern resembling right bundle branch block with an ST segment elevation in leads V1 to V3. In 1998 it was described that the disease is genetically determined with an autosomal dominant pattern of transmission. Three different mutations have been identified. All three mutations affect the structure and the function of the sodium channel SCN5A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443304", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1089, "text": "The diagnosis is easily made by means of the electrocardiogram (ECG). The presence of concealed and intermittent forms, however, makes the diagnosis difficult in some patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 507, "text": "The Brugada syndrome is a clinical-electrocardiographic diagnosis characterised by syncopal or sudden death episodes in patients with a structurally normal heart with a characteristic electrocardiographic pattern consisting of ST segment elevation in the precordial leads V1 to V3 and a morphology of the QRS complex resembling a right bundle branch block. In many patients with the Brugada syndrome, the electrocardiographic manifestations transiently normalize; leading to underdiagnosis of the syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11892423", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 839, "text": "The incidence of sudden death in this syndrome is very high and can only be prevented by implanting a cardioverter-defibrillator. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11892423", "endSection": "abstract" } ] }, { "body": "What is the main component of the Lewy bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23300799", "http://www.ncbi.nlm.nih.gov/pubmed/22843682", "http://www.ncbi.nlm.nih.gov/pubmed/15541000", "http://www.ncbi.nlm.nih.gov/pubmed/20534649", "http://www.ncbi.nlm.nih.gov/pubmed/22923347", "http://www.ncbi.nlm.nih.gov/pubmed/11412709", "http://www.ncbi.nlm.nih.gov/pubmed/20846907", "http://www.ncbi.nlm.nih.gov/pubmed/16969096", "http://www.ncbi.nlm.nih.gov/pubmed/18991634", "http://www.ncbi.nlm.nih.gov/pubmed/23183883", "http://www.ncbi.nlm.nih.gov/pubmed/10327208", "http://www.ncbi.nlm.nih.gov/pubmed/21683963", "http://www.ncbi.nlm.nih.gov/pubmed/21937912", "http://www.ncbi.nlm.nih.gov/pubmed/23382946", "http://www.ncbi.nlm.nih.gov/pubmed/23295909", "http://www.ncbi.nlm.nih.gov/pubmed/15530662", "http://www.ncbi.nlm.nih.gov/pubmed/23562579", "http://www.ncbi.nlm.nih.gov/pubmed/23384565", "http://www.ncbi.nlm.nih.gov/pubmed/11085897", "http://www.ncbi.nlm.nih.gov/pubmed/16951579", "http://www.ncbi.nlm.nih.gov/pubmed/24597591" ], "ideal_answer": [ "Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. Alpha-synuclein has been identified as the main component of the Lewy bodies.", "The main component of Lewy bodies is alpha-synuclein.", "Parkinson s disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis " ], "exact_answer": [ "Alpha-synuclein" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016631", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961" ], "type": "factoid", "id": "550c3d45a103b78016000008", "snippets": [ { "offsetInBeginSection": 350, "offsetInEndSection": 443, "text": "\u03b1-syn is the main component of Lewy bodies in Parkinson's disease (PD) and Lewy body dementia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23562579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23384565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. \u03b1-synuclein is the main component of LB, but the pathological mechanisms that lead to neurodegeneration associated with LB formation remain unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "\u03b1-Synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinson's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 409, "text": "Parkinson's disease (PD) is the second most common neurodegenerative disease. The majority of PD cases are sporadic, for which genetic causes and underlying molecular mechanisms remain largely unclear. Autophagy, a highly conserved cellular process that governs the breakdown of long-lived proteins and organelles, has been involved in the degradation of \u03b1-synuclein (\u03b1-Syn), the main component of Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23295909", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 483, "text": "The main component of Lewy bodies is alpha-synuclein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951579", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 274, "text": "alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15541000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Amyloid precursor protein (APP) is involved in the accumulation of alpha-synuclein, the main component of Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15530662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20534649", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 730, "text": "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that \u03b1-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20846907", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 654, "text": "LBD has neuropathological characteristics whereby numerous Lewy bodies are present in the central and sympathetic nervous systems, and it is a type of alpha-synucleinopathy because the main component of Lewy body is alpha-synuclein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24597591", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 273, "text": "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16969096", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 482, "text": "The main component of Lewy bodies is alpha-synuclein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991634", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 231, "text": "The main component of Lewy bodies is alpha-synuclein (AS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22923347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Amyloid precursor protein (APP) is involved in the accumulation of alpha-synuclein, the main component of Lewy bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15530662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "\ufffd-Synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinsons disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300799", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 834, "text": "In the 1990s, \ufffd-synuclein was identified as the main constituent of the Lewy pathology, and its aggregation was shown to be central to PD, dementia with Lewy bodies, and multiple system atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23183883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Identification of protein interfaces between \ufffd-synuclein, the principal component of Lewy bodies in Parkinson disease, and the molecular chaperones human Hsc70 and the yeast Ssa1p.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22843682", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Fibrillar \ufffd-synuclein (\ufffd-Syn) is the principal component of Lewy bodies, which are evident in individuals affected by Parkinson disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22843682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "\ufffd-Synuclein is a major component of Lewy bodies in Parkinson disease (PD) and dementia with Lewy bodies (DLB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21937912", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 484, "text": "The main component of Lewy bodies is alpha-synuclein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991634", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 274, "text": "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16969096", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 735, "text": "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that \u00ce\u00b1-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20846907", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 273, "text": "alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15541000", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 410, "text": "In Parkinson's disease and Lewy body dementia, alpha-synuclein is the main component of Lewy bodies and dystrophic neurites; alpha-synuclein also accumulates in the cytoplasm of glial cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11412709", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 273, "text": "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16969096", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 231, "text": "The main component of Lewy bodies is alpha-synuclein (AS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22923347", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 732, "text": "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that \u03b1-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20846907", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 272, "text": "alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15541000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "alpha-Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11085897", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 275, "text": "Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10327208", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 287, "text": "Alpha-synuclein (AS) is the main component of Lewy bodies and its aggregation is a key event in the pathogenesis of PD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21683963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The therapeutical potential of alpha-synuclein antiaggregatory agents for dementia with Lewy bodies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991634", "endSection": "title" } ] }, { "body": "How does thyroid hormone regulate mitochondrial biogenesis in the myocardium?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15543939", "http://www.ncbi.nlm.nih.gov/pubmed/17962579", "http://www.ncbi.nlm.nih.gov/pubmed/2773621", "http://www.ncbi.nlm.nih.gov/pubmed/12388124", "http://www.ncbi.nlm.nih.gov/pubmed/19462004", "http://www.ncbi.nlm.nih.gov/pubmed/215035", "http://www.ncbi.nlm.nih.gov/pubmed/20100314", "http://www.ncbi.nlm.nih.gov/pubmed/21568860", "http://www.ncbi.nlm.nih.gov/pubmed/7556180", "http://www.ncbi.nlm.nih.gov/pubmed/22109994", "http://www.ncbi.nlm.nih.gov/pubmed/12734114", "http://www.ncbi.nlm.nih.gov/pubmed/19036942", "http://www.ncbi.nlm.nih.gov/pubmed/1321044", "http://www.ncbi.nlm.nih.gov/pubmed/15893763", "http://www.ncbi.nlm.nih.gov/pubmed/21914860", "http://www.ncbi.nlm.nih.gov/pubmed/20515651", "http://www.ncbi.nlm.nih.gov/pubmed/18575627", "http://www.ncbi.nlm.nih.gov/pubmed/6157679" ], "ideal_answer": [ "T4 increases myocardial mitochondrial bioenergetic capacity, oxygen consumption and markers of mitochondrial biogenesis. The marked, parallel increases in PPARalpha levels suggest its potential involvement in mediating myocardial-specific remodeling of mitochondria in response to T4. T3 induces mitochondrial biogenesis. In fact, T3 treatment for 72h increases activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha). Furthermore, L-T3 increases the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as hypoxic inducible factor-1\u03b1, mitochondrial transcription factor A and peroxisome proliferator activated receptor \u03b3 coactivator-1\u03b1, in the LV peri-infarct zone.\nThe activation of TFAM and TFB2M expression is shown to be required for the induction of mtDNA biogenesis by T3. Truncated forms of the nuclear receptor TR\u03b11, with molecular weights of 43 kDa (p43) and 28 Kda have been previously identified in mitochondria. P43 is a mitochondrial T3 receptor which stimulates mitochondrial transcription and protein synthesis in the presence of T3. p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity." ], "concepts": [ "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002154", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.biosemantics.org/jochem#4250045", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008929", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008928", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006590", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "summary", "id": "515ac941d24251bc050000ab", "snippets": [ { "offsetInBeginSection": 1083, "offsetInEndSection": 1364, "text": "L-T3 significantly increased the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as hypoxic inducible factor-1\u03b1, mitochondrial transcription factor A and peroxisome proliferator activated receptor \u03b3 coactivator-1\u03b1, in the LV peri-infarct zone", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100314", "endSection": "sections.0" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 1918, "text": "the T(3)-induced phosphorylation of p38 and AMPK in both slow- and fast-twitch skeletal muscles suggests that these events may be important in mediating hormone-induced increases in mitochondrial biogenesis in skeletal muscle.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962579", "endSection": "sections.0" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1498, "text": "Our findings indicate parallel increases in myocardial mitochondrial bioenergetic capacity, oxygen consumption and markers of mitochondrial biogenesis with 15-day T4", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15543939", "endSection": "sections.0" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1751, "text": "The marked, parallel increases in PPARalpha levels suggest its potential involvement in mediating myocardial-specific remodeling of mitochondria in response to T4", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15543939", "endSection": "sections.0" }, { "offsetInBeginSection": 1099, "offsetInEndSection": 1287, "text": "T3 mediates an early stimulation of enzymes containing mtDNA encoded subunits (e.g. complex IV and V) in contrast to a different regulatory pattern for the entirely nuclear-encoded enzymes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15893763", "endSection": "sections.0" }, { "offsetInBeginSection": 386, "offsetInEndSection": 682, "text": "Activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha), were significantly elevated with 72 h T3 treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15893763", "endSection": "sections.0" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1209, "text": "T(3) increased PGC-1alpha content similarly in both fast- and slow-twitch muscle, as well as in the liver, but not in heart.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12734114", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Thyroid hormone [3,5,3'-triiodo-l-thyronine (T(3))] induces phenotypic alterations in cardiac mitochondria, in part by influencing protein import and the expression of the import motor mitochondrial heat shock protein (mtHsp70).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12388124", "endSection": "sections.0" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1436, "text": "These findings indicate that import machinery components are differentially regulated in response to stimuli that induce mitochondrial biogenesis, like T(3) and differentiation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12388124", "endSection": "sections.0" }, { "offsetInBeginSection": 159, "offsetInEndSection": 422, "text": "We have previously identified a mitochondrial triiodothyronine receptor (p43) regulating mitochondrial transcription and mitochondrial biogenesis. When overexpressed in skeletal muscle, it increases mitochondrial DNA content, stimulates mitochondrial respiration,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109994", "endSection": "sections.0" }, { "offsetInBeginSection": 548, "offsetInEndSection": 679, "text": "Here we show that a p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity in skeletal muscle", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109994", "endSection": "sections.0" }, { "offsetInBeginSection": 692, "offsetInEndSection": 1147, "text": "The contribution of TFAM, TFB2M, and helicase Twinkle in thyroid-induced mtDNA biogenesis was assessed. The activation of TFAM and TFB2M expression is shown to be required for the induction of mtDNA biogenesis. The role of helicase Twinkle, the expression induction of which is also observed after triiodothyronine addition, remains unclear. The analysis of factors that activate TFAM and TFB2M expression showed that NRF-1 is the determinative regulator:", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21568860", "endSection": "sections.0" }, { "offsetInBeginSection": 558, "offsetInEndSection": 730, "text": "in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1alpha, NRF-1alpha and Tfam", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20515651", "endSection": "sections.0" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1108, "text": "These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20515651", "endSection": "sections.0" }, { "offsetInBeginSection": 1759, "offsetInEndSection": 1942, "text": "T(3) acts to reduce cellular oxidative stress, which may help attenuate ROS-mediated damage, along with improving mitochondrial function and energy status in cells with mtDNA defects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19036942", "endSection": "sections.0" }, { "offsetInBeginSection": 1254, "offsetInEndSection": 1583, "text": "These findings suggest the existence of compensatory mechanisms operating at the translational and/or post-translational levels which promote proliferation of mitochondria in the hypothyroid liver. However, when the liver mass was considered, hypothyroidism significantly reduced overall mitochondrial proliferation in rat liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7556180", "endSection": "sections.0" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1595, "text": "Total liver mitochondrial DNA levels in thyroid-treated animals were greater than age-paired controls by 79% at 7 days but only 67% at 14 days since a small gain occurred in control animals and no further increase occurred in treated rats during the second week.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6157679", "endSection": "sections.0" }, { "offsetInBeginSection": 1809, "offsetInEndSection": 1917, "text": "thyroid hormone treatment produces hyperplasia and an increase in mitochondrial number and mass in rat liver", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6157679", "endSection": "sections.0" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1340, "text": "It is concluded that T3 exerts a direct, rather than permissive, effect on mitochondrial biogenesis, and that high affinity binding sites for GH are not present in rat liver mitochondria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2773621", "endSection": "sections.0" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1248, "text": "These data strengthen the view that thyroid hormone regulates synthesis of specific components within each respiratory-chain complex and that these products apparently play key roles in inner-membrane biogenesis and assembly", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1321044", "endSection": "sections.0" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1312, "text": "It is concluded that thyroid hormone causes an increase in the mitochondrial mass, mitochondrial cytochrome content, and respiratory rate, and consequently expands the capacity of oxidative metabolism without an uncoupling effect on oxidative phosphorylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/215035", "endSection": "sections.0" } ] }, { "body": "What is the link between HOT regions and RNA polymerase recruitment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24138567" ], "ideal_answer": [ "Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance." ], "exact_answer": [ "Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012320", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012318", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012321", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012319" ], "type": "factoid", "id": "56ae2fab0a360a5e45000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "title" }, { "offsetInBeginSection": 422, "offsetInEndSection": 787, "text": "Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1360, "text": "CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 525, "text": "We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 768, "text": "Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 896, "text": "At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1337, "text": "Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 525, "text": "We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1337, "text": "Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138567", "endSection": "abstract" } ] }, { "body": "List variants of the MC1R gene.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24170137", "http://www.ncbi.nlm.nih.gov/pubmed/25219681", "http://www.ncbi.nlm.nih.gov/pubmed/26103569", "http://www.ncbi.nlm.nih.gov/pubmed/24917043" ], "ideal_answer": [ "V60L\nD84E\nV92M\nR151C\nR160W\nR163Q\nD294H" ], "exact_answer": [ [ "V60L" ], [ "D84E" ], [ "V92M" ], [ "R151C" ], [ "R160W" ], [ "R163Q" ], [ "D294H" ] ], "type": "list", "id": "570a5343cf1c325851000022", "snippets": [ { "offsetInBeginSection": 873, "offsetInEndSection": 1131, "text": "All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26103569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The melanocortin 1 receptor (MC1R) gene encodes for a seven-pass transmembrane receptor primarily expressed on melanocytes and melanoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25219681", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 755, "text": "for V60L to 2.74 (1.53-4.89) for D84E. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24917043", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 305, "text": " We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170137", "endSection": "abstract" } ] }, { "body": "Which is the enzyme that degrades decapped mRNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24510189", "http://www.ncbi.nlm.nih.gov/pubmed/22383165" ], "ideal_answer": [ "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1", "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1." ], "exact_answer": [ "XRN1" ], "type": "factoid", "id": "56cdf5315795f9a73e000046", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510189", "endSection": "abstract" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1227, "text": "DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "XRN1 is a 5' \u2192 3' processive exoribonuclease that degrades mRNAs after they have been decapped", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383165", "endSection": "abstract" } ] }, { "body": "Which phenotypes are associated with heterozygous mutations of the BSCL2 gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17387721", "http://www.ncbi.nlm.nih.gov/pubmed/20598714", "http://www.ncbi.nlm.nih.gov/pubmed/17633104", "http://www.ncbi.nlm.nih.gov/pubmed/14981520", "http://www.ncbi.nlm.nih.gov/pubmed/20806400", "http://www.ncbi.nlm.nih.gov/pubmed/17663003", "http://www.ncbi.nlm.nih.gov/pubmed/15242882" ], "ideal_answer": [ "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.", "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement" ], "exact_answer": [ [ "Silver syndrome/spastic paraplegia 17" ], [ "Distal hereditary motor neuropathy type V" ], [ "Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement" ] ], "type": "list", "id": "5713b29f1174fb175500000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20806400", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 392, "text": "Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17663003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20806400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17633104", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 670, "text": "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15242882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Distal hereditary motor neuropathy type V (dHMN-V) and Silver syndrome are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) gene or Seipin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14981520", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Heterozygous mutations in the Seipin/BSCL2 gene have recently been identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V and Silver's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387721", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 484, "text": "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15242882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14981520", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17633104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20806400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20806400", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 574, "text": "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V). Here we report the clinical features of two families with heterozygous BSCL2 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15242882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20806400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14981520", "endSection": "title" }, { "offsetInBeginSection": 299, "offsetInEndSection": 486, "text": "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15242882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17633104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Heterozygous mutations in the Seipin/BSCL2 gene have recently been identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V and Silver's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387721", "endSection": "abstract" } ] }, { "body": "Which is the target protein of the drug nivolumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "http://www.ncbi.nlm.nih.gov/pubmed/26448890", "http://www.ncbi.nlm.nih.gov/pubmed/26273207", "http://www.ncbi.nlm.nih.gov/pubmed/26027431", "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "http://www.ncbi.nlm.nih.gov/pubmed/26406148" ], "ideal_answer": [ "Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation." ], "exact_answer": [ "programmed death receptor-1" ], "type": "factoid", "id": "56f780cb09dd18d46b000011", "snippets": [ { "offsetInBeginSection": 280, "offsetInEndSection": 372, "text": "nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 72, "text": " Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26027431", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 188, "text": "Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "endSection": "abstract" }, { "offsetInBeginSection": 46, "offsetInEndSection": 173, "text": " programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26448890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26273207", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 72, "text": "Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26406148", "endSection": "abstract" } ] }, { "body": "The CXCR2 receptor is targeted in cancer. Name five antagonists.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15623601", "http://www.ncbi.nlm.nih.gov/pubmed/19549892", "http://www.ncbi.nlm.nih.gov/pubmed/15805273", "http://www.ncbi.nlm.nih.gov/pubmed/22590561", "http://www.ncbi.nlm.nih.gov/pubmed/21328342", "http://www.ncbi.nlm.nih.gov/pubmed/19809428", "http://www.ncbi.nlm.nih.gov/pubmed/17634442", "http://www.ncbi.nlm.nih.gov/pubmed/18289803", "http://www.ncbi.nlm.nih.gov/pubmed/20967859", "http://www.ncbi.nlm.nih.gov/pubmed/23204236", "http://www.ncbi.nlm.nih.gov/pubmed/11700073", "http://www.ncbi.nlm.nih.gov/pubmed/20652010", "http://www.ncbi.nlm.nih.gov/pubmed/23019013", "http://www.ncbi.nlm.nih.gov/pubmed/16540656", "http://www.ncbi.nlm.nih.gov/pubmed/21670971", "http://www.ncbi.nlm.nih.gov/pubmed/18790747", "http://www.ncbi.nlm.nih.gov/pubmed/18780829", "http://www.ncbi.nlm.nih.gov/pubmed/22391039", "http://www.ncbi.nlm.nih.gov/pubmed/23359652", "http://www.ncbi.nlm.nih.gov/pubmed/12244149", "http://www.ncbi.nlm.nih.gov/pubmed/12753603", "http://www.ncbi.nlm.nih.gov/pubmed/19293256", "http://www.ncbi.nlm.nih.gov/pubmed/21035946" ], "ideal_answer": [ "There are numerous CXCR2 receptor antagonists, such as SB225002, G31P, SCH-527123, AZ10397767, SCH-479833." ], "exact_answer": [ [ "SB225002" ], [ "G31P" ], [ "SCH-527123" ], [ "AZ10397767" ], [ "SCH-479833" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0048019", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006605", "http://www.uniprot.org/uniprot/CXCR2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045238", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046817", "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "list", "id": "5141bcd423fec9037500000d", "snippets": [ { "offsetInBeginSection": 517, "offsetInEndSection": 559, "text": "CXCR2 small-molecule antagonist (SB225002)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204236", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "G31P, an antagonist against CXC chemokine receptors 1 and 2, inhibits growth of human prostate cancer cells in nude mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23019013", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "The CXCR2 antagonist, SCH-527123, shows antitumor activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22391039", "endSection": "title" }, { "offsetInBeginSection": 761, "offsetInEndSection": 809, "text": "retreatment with the CXCR2 antagonist AZ10397767", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18790747", "endSection": "sections.0" }, { "offsetInBeginSection": 477, "offsetInEndSection": 690, "text": "The aim of this study was to investigate whether the CXCR2 antagonist, SCH-527123, inhibits colorectal cancer proliferation and if it can sensitize colorectal cancer cells to oxaliplatin both in vitro and in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22391039", "endSection": "sections.0" }, { "offsetInBeginSection": 196, "offsetInEndSection": 441, "text": "we report that targeting CXCR2 and CXCR1 activity using orally active small molecule antagonist (SCH-527123, SCH-479833) inhibits human colon cancer liver metastasis mediated by decreased neovascularization and enhanced malignant cell apoptosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035946", "endSection": "sections.0" }, { "offsetInBeginSection": 593, "offsetInEndSection": 720, "text": "CXCR2-specific small molecule inhibitor (AZ10397767) to investigate the recruitment and function of human neutrophils in tumors", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21328342", "endSection": "sections.0" } ] }, { "body": "What is the genomic structure of the FAA (FANCA) gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9169126" ], "ideal_answer": [ "The FAA (FANCA) gene contains 43 exons spanning approximately 80 kb. Exons range from 34 to 188 bp, whereas sequence analysis of the 5' region upstream of the putative transcription start site showed no obvious TATA and CAAT boxes, but did show a GC-rich region, typical of housekeeping genes." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052217" ], "type": "summary", "id": "54edf27e94afd61504000010", "snippets": [ { "offsetInBeginSection": 249, "offsetInEndSection": 553, "text": "In the present study we describe the genomic structure of the FAA gene. The gene contains 43 exons spanning approximately 80 kb as determined by the alignment of four cosmids and the fine localization of the first and the last exons in restriction fragments of these clones. Exons range from 34 to 188 bp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9169126", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1011, "text": "Sequence analysis of the 5' region upstream of the putative transcription start site showed no obvious TATA and CAAT boxes, but did show a GC-rich region, typical of housekeeping genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9169126", "endSection": "abstract" } ] }, { "body": "What is Snord116?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24311433", "http://www.ncbi.nlm.nih.gov/pubmed/18320030", "http://www.ncbi.nlm.nih.gov/pubmed/22694955", "http://www.ncbi.nlm.nih.gov/pubmed/22495932", "http://www.ncbi.nlm.nih.gov/pubmed/21880592", "http://www.ncbi.nlm.nih.gov/pubmed/20803659", "http://www.ncbi.nlm.nih.gov/pubmed/22664655", "http://www.ncbi.nlm.nih.gov/pubmed/20588305" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11643850", "o": "HUGO" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11710462", "o": "HBII-85" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/label/A17735607" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/label/A14197897" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/label/A11717071" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/label/A11710462" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/label/A17735606" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14197897", "o": "PET1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11643850", "o": "small nucleolar RNA, C/D box 116 cluster" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17735607", "o": "SNORD116@ gene cluster" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/label/A11643850" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17735606", "o": "SNORD116@" }, { "p": 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"http://linkedlifedata.com/resource/umls/label/A17735606", "o": "32781" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17735607", "o": "32781" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11717071", "o": "Metathesaurus Names" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/relation/R115185196" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/relation/R58817161" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R115185196", "o": "http://linkedlifedata.com/resource/umls/id/C1823072" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R91971052", "o": "http://linkedlifedata.com/resource/umls/id/C1823072" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R115153156", "o": "http://linkedlifedata.com/resource/umls/id/C1823072" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1823072", "o": "http://linkedlifedata.com/resource/umls/relation/R91978740" } ], "ideal_answer": [ "SNORD116 is a small nucleolar (sno) RNA gene cluster (HBII-85) implicated as a major contributor the Prader-Willi phenotype. \nSNORD116 genes appears to be responsible for the major features of PWS. \nSNORD116 is a paternally expressed box C/D snoRNA gene cluster.\nThe mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs.\nSnord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally.\nSnord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058727", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020537" ], "type": "summary", "id": "52b2f1014003448f5500000a", "snippets": [ { "offsetInBeginSection": 357, "offsetInEndSection": 603, "text": "Further analysis with array-CGH identified a mosaic 847\u2009kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and B), SNORD64 (HBII-13), and NPAP1 (C15ORF2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311433", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1242, "text": "All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311433", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 281, "text": "Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22694955", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 1497, "text": "Small nucleolar (sno) RNAs are a group of small RNAs located in nucleoli that modulate chemical modifications and maturation of ribosomal or other RNAs. Recent data suggest that snoRNA Snord116 is important for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia and obesity. The current study was conducted to assess a potential cellular link between Snord116 and phenotypes of PWS. Data from mice revealed Snord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "The imprinted Snurf-Snrpn chromosomal domain contains two large arrays of tandemly repeated, paternally expressed box C/D small-nucleolar RNA (snoRNA) genes: the SNORD115 (H/MBII-52) and SNORD116 (H/MBII-85) gene clusters believed to play key roles in the fine-tuning of serotonin receptor (5-HT2C) pre-mRNA processing and in the etiology of the Prader-Willi Syndrome (PWS), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495932", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 312, "text": "We demonstrate that the mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880592", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 377, "text": "Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20803659", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 711, "text": "In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20588305", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1684, "text": " Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20588305", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 571, "text": "Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18320030", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 1814, "text": "Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18320030", "endSection": "abstract" } ] }, { "body": "What is the functional role of the protein Drp1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17015472", "http://www.ncbi.nlm.nih.gov/pubmed/23027751", "http://www.ncbi.nlm.nih.gov/pubmed/22334657", "http://www.ncbi.nlm.nih.gov/pubmed/23888838", "http://www.ncbi.nlm.nih.gov/pubmed/23904108", "http://www.ncbi.nlm.nih.gov/pubmed/20850011", "http://www.ncbi.nlm.nih.gov/pubmed/22020994", "http://www.ncbi.nlm.nih.gov/pubmed/25658204", "http://www.ncbi.nlm.nih.gov/pubmed/23334860", "http://www.ncbi.nlm.nih.gov/pubmed/16684605", "http://www.ncbi.nlm.nih.gov/pubmed/25012575", "http://www.ncbi.nlm.nih.gov/pubmed/22703557", "http://www.ncbi.nlm.nih.gov/pubmed/24080278", "http://www.ncbi.nlm.nih.gov/pubmed/19638400", "http://www.ncbi.nlm.nih.gov/pubmed/23128392", "http://www.ncbi.nlm.nih.gov/pubmed/25348719", "http://www.ncbi.nlm.nih.gov/pubmed/25036098", "http://www.ncbi.nlm.nih.gov/pubmed/24388463", "http://www.ncbi.nlm.nih.gov/pubmed/20649536", "http://www.ncbi.nlm.nih.gov/pubmed/25332205", "http://www.ncbi.nlm.nih.gov/pubmed/24485837", "http://www.ncbi.nlm.nih.gov/pubmed/24878071", "http://www.ncbi.nlm.nih.gov/pubmed/20179104", "http://www.ncbi.nlm.nih.gov/pubmed/15791210", "http://www.ncbi.nlm.nih.gov/pubmed/25192600", "http://www.ncbi.nlm.nih.gov/pubmed/24764190", "http://www.ncbi.nlm.nih.gov/pubmed/22367970", "http://www.ncbi.nlm.nih.gov/pubmed/24755420", "http://www.ncbi.nlm.nih.gov/pubmed/24631294", "http://www.ncbi.nlm.nih.gov/pubmed/24616159", "http://www.ncbi.nlm.nih.gov/pubmed/21613270", "http://www.ncbi.nlm.nih.gov/pubmed/21459773", "http://www.ncbi.nlm.nih.gov/pubmed/25237193", "http://www.ncbi.nlm.nih.gov/pubmed/26038571", "http://www.ncbi.nlm.nih.gov/pubmed/24302731" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0112997", "o": "D012380" } ], "ideal_answer": [ "Drp1 is involved in the regulation of mitochondrial fission.", "Dynamin-related protein 1 (Drp1) mediates mitochondrial fission." ], "exact_answer": [ "mitochondrial fission" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024101", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380" ], "type": "factoid", "id": "5717dbfe7de986d80d000001", "snippets": [ { "offsetInBeginSection": 239, "offsetInEndSection": 318, "text": "dynamin-related protein 1 (Drp1), a GTPase that mediates mitochondrial fission,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332205", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 389, "text": "dynamin-related protein 1 (DRP1), a protein required for mitochondrial network division.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25658204", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 370, "text": "dynamin-related protein 1 (Drp1)-mediated mitochondrial fission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26038571", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 192, "text": "Mitochondrial fission is mediated by dynamin-related protein 1 (Drp1),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25192600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25237193", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 698, "text": "Mitochondrial fission requires the dynamin GTPase Drp1, which assembles in a ring around the mitochondrion and appears to constrict both outer and inner mitochondrial membranes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24485837", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 304, "text": "DRP1; a mitochondrial fission protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24631294", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 446, "text": "Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012575", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 617, "text": "The change in mitochondrial morphology was caused by downregulation of the expression of Fis1 and Drp1, two proteins regulating mitochondrial fission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20179104", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1645, "text": "Furthermore, overexpression of the fission protein Drp1 (dynamin-related protein 1) or knocking down of the fusion protein OPA1 (optical atrophy 1) suppressed PINK1 RNAi-induced mitochondrial morphological defect, and overexpression of PINK1 or Parkin suppressed the elongated mitochondria phenotype caused by Drp1 RNAi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21613270", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1054, "text": "These results collectively indicate that ER-specific BNIP1 plays an important role in mitochondrial dynamics by modulating the mitochondrial fission protein Drp1 in a BH3 domain-dependent fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020994", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 710, "text": "In the present study, we found a marked upregulation of mitochondrial fission protein dynamin-related protein 1 (Drp1) expression in human invasive breast carcinoma and metastases to lymph nodes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23128392", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1367, "text": "Mitochondrial remodeling was associated with increased proximity between Rab11a and mitochondrial membranes, changes in fusion-fission dynamics, and mitochondrial relocalization of the fission factor dynamin-related protein 1 (Drp1), which was regulated by the Rab11a effector protein FIP1/RCP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24302731", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 750, "text": "Functional analysis demonstrated that BNIP1 expression increased dynamin-related protein 1 (Drp1) expression followed by the mitochondrial translocation of Drp1 and subsequent mitochondrial fission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334860", "endSection": "title" }, { "offsetInBeginSection": 109, "offsetInEndSection": 227, "text": "In this study the role of the mitochondrial fission protein, Drp1 during Shigella infection in HeLa cells was examined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24755420", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 403, "text": "In this study, we investigate the role of mitochondrial fission factor dynamin-related protein 1 (Drp1) in myogenic differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23904108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334860", "endSection": "title" }, { "offsetInBeginSection": 356, "offsetInEndSection": 553, "text": "Functional analysis demonstrated that BNIP1 expression increased dynamin-related protein 1 (Drp1) expression followed by the mitochondrial translocation of Drp1 and subsequent mitochondrial fission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020994", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 861, "text": "These results collectively indicate that ER-specific BNIP1 plays an important role in mitochondrial dynamics by modulating the mitochondrial fission protein Drp1 in a BH3 domain-dependent fashion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Glucocorticoid modulation of mitochondrial function in hepatoma cells requires the mitochondrial fission protein Drp1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22703557", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Mitochondria in DRG neurons undergo hyperglycemic mediated injury through Bim, Bax and the fission protein Drp1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16684605", "endSection": "title" }, { "offsetInBeginSection": 577, "offsetInEndSection": 680, "text": "This novel function for DRP1 is distinct from its recognized role in regulating mitochondrial fission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15791210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer's disease neurons: implications for mitochondrial dysfunction and neuronal damage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22367970", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19638400", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20649536", "endSection": "title" }, { "offsetInBeginSection": 397, "offsetInEndSection": 546, "text": "We highlight posttranslational modifications of the mitochondrial fission protein Drp1, for which these regulatory mechanisms are best characterized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20649536", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1476, "text": "Furthermore, overexpression of the fission protein Drp1 (dynamin-related protein 1) or knocking down of the fusion protein OPA1 (optical atrophy 1) suppressed PINK1 RNAi-induced mitochondrial morphological defect, and overexpression of PINK1 or Parkin suppressed the elongated mitochondria phenotype caused by Drp1 RNAi. Functionally, PINK1 knockdown and overexpression had opposite effects on dendritic spine formation and neuronal vulnerability to excitotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21613270", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 229, "text": "In this study the role of the mitochondrial fission protein, Drp1 during Shigella infection in HeLa cells was examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24755420", "endSection": "abstract" } ] }, { "body": "Which is the genetic cause for the development of Fanconi anemia complementation group D1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15695377", "http://www.ncbi.nlm.nih.gov/pubmed/15645491", "http://www.ncbi.nlm.nih.gov/pubmed/18212739", "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "http://www.ncbi.nlm.nih.gov/pubmed/14695169", "http://www.ncbi.nlm.nih.gov/pubmed/12383764", "http://www.ncbi.nlm.nih.gov/pubmed/16920162" ], "ideal_answer": [ "Fanconi anemia complementation group D1 (FANCD1) was shown to be induced by biallelic mutations in the BRCA2 breast-cancer-susceptibility gene." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.uniprot.org/uniprot/BRCA2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024682" ], "type": "summary", "id": "54ede34694afd61504000004", "snippets": [ { "offsetInBeginSection": 155, "offsetInEndSection": 327, "text": "The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16920162", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 679, "text": "Although he lacked a strong family history of cancer, he was subsequently shown to carry biallelic mutations in the FANCD1/BRCA2 gene. These included an IVS7 splice-site mutation, which is strongly associated with early AML in homozygous or compound heterozygous carrier status in FA-D1 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15645491", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 317, "text": "Biallelic BRCA2 mutations were shown recently to cause FA-D1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14695169", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 265, "text": "The breast cancer susceptibility gene BRCA2 was recently found to be associated with Fanconi anemia complementation group D1 (FA-D1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 576, "text": "One kindred, of Ashkenazi Jewish ancestry, had five members who were diagnosed with breast cancer and two cousins who were BRCA2*6174delT/C3069X compound heterozygotes and had Fanconi anemia and brain tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 752, "text": "In another kindred of Ashkenazi Jewish and Lithuanian Catholic ancestry, a child with Fanconi anemia and a medulloblastoma was a BRCA2*6174delT/886delGT compound heterozygote", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 1034, "text": "Two other kindreds each contained a Fanconi anemia-afflicted child who developed medulloblastoma; one child was of Latin American ancestry and a compound heterozygote for BRCA2*I2490T/ 5301insA and the other was African American and a compound heterozygote for BRCA2*Q3066X/E1308X", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Surprisingly, biallelic mutations in the BRCA2 breast-cancer-susceptibility gene were found in Fanconi anemia (FA), a rare hereditary disorder characterized by chromosomal instability, hypersensitivity to DNA cross-linking agents, and cancer susceptibility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12383764", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 265, "text": " The breast cancer susceptibility gene BRCA2 was recently found to be associated with Fanconi anemia complementation group D1 (FA-D1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Biallelic mutations in Fanconi anemia complementation group genes disrupt DNA repair and result in the complex Fanconi anemia phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15695377", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 254, "text": "Thirteen complementation groups and genes are identified, including BRCA2, which is defective in the FA-D1 group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18212739", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 316, "text": "Biallelic BRCA2 mutations were shown recently to cause FA-D1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14695169", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 315, "text": "Biallelic BRCA2 mutations were shown recently to cause FA-D1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14695169", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 253, "text": "Thirteen complementation groups and genes are identified, including BRCA2, which is defective in the FA-D1 group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18212739", "endSection": "abstract" } ] }, { "body": "Which diseases are caused by mutations in Calsequestrin 2 (CASQ2) gene?", "documents": [ 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"http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51375A574D300011", "o": "casq1" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_51375A574D300011", "o": "casq2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51375A574D3000C", "o": "Calsequestrin" } ], "ideal_answer": [ "CASQ2 mutations are associated with autosomal recessive catecholaminergic polymorphic ventricular tachycardia (CPVT) and familial hypertrophic cardiomyopathy.", "Mutations in the gene encoding for cardiac calsequestrin, CASQ2, cause a rare but severe form of catecholaminergic polymorphic ventricular tachycardia (CPVT).\nThere is also a publication that links mutations in CASQ2 gene to the disease of hypertrophic cardiomyopathy (HCM)." ], "exact_answer": [ [ "catecholaminergic polymorphic ventricular tachycardia (CPVT)", "CPVT", "catecholaminergic polymorphic ventricular tachycardia" ], [ "familial hypertrophic cardiomyopathy", "HCM", "hypertrophic cardiomyopathy" ] ], "concepts": [ "http://www.uniprot.org/uniprot/CASQ2_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.uniprot.org/uniprot/CASQ2_PIG", "http://www.uniprot.org/uniprot/CASQ2_PONAB", "http://www.uniprot.org/uniprot/CASQ2_HUMAN", "http://www.uniprot.org/uniprot/CASQ2_CANFA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/CASQ2_RAT", "http://www.uniprot.org/uniprot/CASQ2_RABIT", "http://www.uniprot.org/uniprot/CASQ2_MOUSE" ], "type": "list", "id": "52bf1af803868f1b06000008", "snippets": [ { "offsetInBeginSection": 136, "offsetInEndSection": 507, "text": "Recessively inherited CPVT is caused by either missense or null-allele mutations in the cardiac calsequestrin (CASQ2) gene. It was suggested that defects in CASQ2 cause protein deficiency and impair Ca(2+) uptake to the sarcoplasmic reticulum and Ca(2+)-dependent inhibition of ryanodine channels, leading to diastolic Ca(2+) leak, after-depolarizations, and arrhythmia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23042908", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 473, "text": "The autosomal recessive form of CPVT is caused by mutations in the CASQ2 gene. In a consanguineous family, a novel homozygous CASQ2 mutation (p.L77P) was identified in a child with CPVT who required implantation of a cardioverter defibrillator due to episodes of syncope while on medical therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Catecholaminergic polymorphic ventricular tachycardia is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22557844", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 298, "text": "Thirteen mutations in the CASQ2 gene have been reported so far in association with CPVT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21618644", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 1204, "text": "These data increased significantly the number of CASQ2 mutations described in association with CPVT, revealed the high prevalence of splicing and truncating mutations in this gene and brought new insight regarding the dominant inheritance of the disease. Moreover, our report of the first splicing abnormalities in CASQ2 caused by intronic mutation or synonymous change underlines the absolute necessity to perform extensive molecular analysis for genetic diagnosis and counseling of CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21618644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Mutations in the human cardiac calsequestrin gene (CASQ2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT-2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20302875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19568611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 488, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death. Two genes involved in calcium homeostasis, the ryanodine receptor gene and the calsequestrin 2 (CASQ2) gene, have been implicated in this disease. We describe a young man presenting with exercise-induced syncope, clinically diagnosed as CPVT. Genetic analysis revealed two mutations, p.Y55C (c.164A>G) and p.P308L (c.923C>T), in the CASQ2 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18684293", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 369, "text": "A novel heterozygous mutation, F189L, in CASQ2 gene was identified in one family with CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18543230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Catecholamine-induced polymorphic ventricular tachycardia (CPVT) is a familial disorder caused by cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) gene mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17607358", "endSection": "abstract" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1225, "text": "We conclude that CPVT-causing CASQ2 missense mutations function as null alleles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17607358", "endSection": "abstract" }, { "offsetInBeginSection": 1594, "offsetInEndSection": 1813, "text": "The central role of RyR2 dysfunction in CASQ2 deficiency unifies the pathophysiologic mechanism underlying CPVT due to RyR2 or CASQ2 mutations and suggests a therapeutic approach for these inherited cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17607358", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1172, "text": "Mutations of the RyR2 gene cause autosomal dominant CPVT, while mutations of the CASQ2 gene may cause an autosomal recessive or dominant form of CPVT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15913575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting with salvoes of exercise-induced bidirectional and polymorphic tachycardias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14571276", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 1054, "text": "These data, combined with our previous findings, show that RYR2 mutations are present in at least 6/16 (38%) of the catecholaminergic polymorphic ventricular tachycardia families, while CASQ2 mutations must be a rare cause of CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14571276", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 375, "text": "This report reviews evidence that a missense mutation in the CASQ2 gene is associated with autosomal-recessive CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12732448", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 1213, "text": "An Australian cohort of 252 unrelated familial hypertrophic cardiomyopathy patients were screened for mutations in the Ca(2+) regulatory genes, sorcin (SRI), calstabin (FKBP1B), calsequestrin (CASQ2), phospholamban (PLN), sarcolipin (SLN), calreticulin (CALR3) and calmodulin (CALM). A total of 17 exonic DNA variants were identified in the 7 Ca(2+) regulatory genes studied, of which 4 were considered of pathogenic significance. Two novel mutations in the CALR3 gene were identified (Lys82Arg, Arg73Gln) and one truncation mutation in the PLN gene (Leu39Ter). A variant was also identified in the CASQ2 gene (Asp63Glu). These four variants were all novel, resulted in changes in conserved amino acids and were not identified in a normal population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17655857", "endSection": "abstract" } ] }, { "body": "What are the most frequent non-canonical sequence motifs at the donor and acceptor splice sites in vertebrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21079731", "http://www.ncbi.nlm.nih.gov/pubmed/17082203", "http://www.ncbi.nlm.nih.gov/pubmed/11058137", "http://www.ncbi.nlm.nih.gov/pubmed/11125105", "http://www.ncbi.nlm.nih.gov/pubmed/20163699", "http://www.ncbi.nlm.nih.gov/pubmed/16267086", "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "http://www.ncbi.nlm.nih.gov/pubmed/11574683" ], "ideal_answer": [ "There are two major exceptions to the canonical GT-AG dinucleotides at donor and acceptor sites: the GG-AG splice site pairs, recognized through the typical U2 splicing machinery, and the AT-AC splice pairs recognized by the U12 splicing machinery." ], "type": "summary", "id": "517575558ed59a060a00002d", "snippets": [ { "offsetInBeginSection": 170, "offsetInEndSection": 356, "text": "About 1-2% of introns are non-canonical, with the most abundant subtype of non-canonical introns being characterized by GC and AG dinucleotides at their 5'- and 3'-termini, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "endSection": "sections.0" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1147, "text": "Our results indicate that the incorporation of non-canonical splice site models yields dramatic improvements in annotating genes containing GC-AG and AT-AC non-canonical introns", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "endSection": "sections.0" }, { "offsetInBeginSection": 1614, "offsetInEndSection": 1903, "text": "If we assume that approximately the same situation is true for the whole set of annotated mammalian non-canonical splice sites, then the 99.24% of splice site pairs should be GT-AG, 0.69% GC-AG, 0.05% AT-AC and finally only 0.02% could consist of other types of non-canonical splice sites.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11058137", "endSection": "sections.0" } ] }, { "body": "What does isradipine do to L-type channels?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17311846", "http://www.ncbi.nlm.nih.gov/pubmed/17218348", "http://www.ncbi.nlm.nih.gov/pubmed/20816785", "http://www.ncbi.nlm.nih.gov/pubmed/11285265", "http://www.ncbi.nlm.nih.gov/pubmed/21515375", "http://www.ncbi.nlm.nih.gov/pubmed/11283860", "http://www.ncbi.nlm.nih.gov/pubmed/18996099", "http://www.ncbi.nlm.nih.gov/pubmed/9398449", "http://www.ncbi.nlm.nih.gov/pubmed/19385055", "http://www.ncbi.nlm.nih.gov/pubmed/8178970", "http://www.ncbi.nlm.nih.gov/pubmed/17884683", "http://www.ncbi.nlm.nih.gov/pubmed/7978480", "http://www.ncbi.nlm.nih.gov/pubmed/21487241", "http://www.ncbi.nlm.nih.gov/pubmed/21925266", "http://www.ncbi.nlm.nih.gov/pubmed/9585150" ], "ideal_answer": [ "Isradipine antagonizes/blocks the L-type channels." ], "exact_answer": [ "antagonizes", "blocks" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020746", "http://www.biosemantics.org/jochem#4250298", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017275" ], "type": "factoid", "id": "56cf20eb3975bb303a000001", "snippets": [ { "offsetInBeginSection": 514, "offsetInEndSection": 641, "text": "The L-type channel blocker, isradipine (5 microM), had no significant effect on the amplitude or kinetics of the Ca(2+) signal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18996099", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 1047, "text": "A comparison of the sensitivity to blockade by isradipine of the L-type currents in Purkinje cells and ventricular epicardial myocytes, which only express Ca(v)1.2, suggests that the Ca(v)1.3 channels make, at most, a minor contribution to the L-type current in canine Purkinje cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17218348", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1326, "text": "Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker omega-conotoxin GVIA, but not by the L-type channel blocker isradipine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17311846", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 991, "text": "Systemic administration of isradipine, a dihydropyridine blocker of L-type channels, forces dopaminergic neurons in rodents to revert to a juvenile, Ca(2+)-independent mechanism to generate autonomous activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17884683", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 603, "text": "The release of glutamate was significantly inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9585150", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 836, "text": "What distinguishes snail and mammalian L-type channels is a difference in dihydropyridine sensitivity: 100 nM isradipine exhibits a significant block of mammalian Ca(v) 1.2 currents without effect on snail LCa(v)1 currents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21487241", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1326, "text": "A comparison of the sensitivity to blockade by isradipine of the L-type currents in Purkinje cells and ventricular epicardial myocytes, which only express Ca(v)1.2, suggests that the Ca(v)1.3 channels make, at most, a minor contribution to the L-type current in canine Purkinje cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17218348", "endSection": "abstract" }, { "offsetInBeginSection": 1319, "offsetInEndSection": 1496, "text": "Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker omega-conotoxin GVIA, but not by the L-type channel blocker isradipine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17311846", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 987, "text": "During control stimulation of the presynaptic GABAergic neuron at 40 Hz for 1-2 s, DeltaF/F(0) increased rapidly to a peak value and started to decline shortly after the train ended, returning to baseline within 10-20 s. The L-type channel blocker, isradipine (5 microM), had no significant effect on the amplitude or kinetics of the Ca(2+) signal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18996099", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 773, "text": "The release of glutamate was significantly inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9585150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21515375", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20816785", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Effects of isradipine, an L-type calcium channel blocker on permanent and transient focal cerebral ischemia in spontaneously hypertensive rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9398449", "endSection": "title" }, { "offsetInBeginSection": 431, "offsetInEndSection": 750, "text": "The release of glutamate was significantly inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist. Omega-conotoxin GVIA, an N type calcium channel antagonist and flunarizine, a nonselective T-type calcium channel antagonist were without effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9585150", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1479, "text": "Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker omega-conotoxin GVIA, but not by the L-type channel blocker isradipine. These data showed that selective functional coupling between N-type Ca(2+) and BK channels provided rapid activation of BK channels in central neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17311846", "endSection": "abstract" } ] }, { "body": "Why does cranberry juice help combat urinary tract infections?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21688109", "http://www.ncbi.nlm.nih.gov/pubmed/19921981", "http://www.ncbi.nlm.nih.gov/pubmed/9110682", "http://www.ncbi.nlm.nih.gov/pubmed/21480803", "http://www.ncbi.nlm.nih.gov/pubmed/19636526", "http://www.ncbi.nlm.nih.gov/pubmed/19257836", "http://www.ncbi.nlm.nih.gov/pubmed/20495471", "http://www.ncbi.nlm.nih.gov/pubmed/23440506", "http://www.ncbi.nlm.nih.gov/pubmed/24304610", "http://www.ncbi.nlm.nih.gov/pubmed/19284180", "http://www.ncbi.nlm.nih.gov/pubmed/22499815" ], "ideal_answer": [ "Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029799", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014552", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014551" ], "type": "summary", "id": "5314ad66dae131f847000004", "snippets": [ { "offsetInBeginSection": 1339, "offsetInEndSection": 1486, "text": " Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19257836", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 435, "text": " Cranberry juice has been shown to be effective in preventing adhesion of bacteria such as Escherichia coli to the bladder epithelium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22499815", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 1014, "text": "Inhibition of adherence to an extent of about 70% with multi-drug resistant E. coli strains was observed on uroepithelial cell. The anti-adherence bioactivity of the proanthocyanidin was detected at concentrations of 10-50 \u00b5g/ml with significant bacteriuria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21688109", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1156, "text": "Still with regard to antibiotic treatment in women, a recently published study investigated also the potential cranberry juice interaction with beta-lactam antibiotics supporting the hypothesis that cranberry juice in usual quantities as prophylaxis for UTI is not likely to alter the pharmacokinetics of these oral antibiotics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20495471", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 781, "text": "In vitro studies have shown that binding of the P fimbriae of Escherichia coli to the uroepithelial tissue can be inhibited in the presence of proanthocyanidins, the active ingredient of cranberries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19636526", "endSection": "abstract" }, { "offsetInBeginSection": 918, "offsetInEndSection": 1172, "text": "NDM at concentrations between 0.2/mL and 1mg/mL significantly (P<.05) decreased secretion of extracellular FTF, as well as down-regulated ftf expression in a dose-dependent manner. NDM also markedly reduced the luciferase activity under the ftf promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19284180", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 189, "text": "Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary tract infections. Its proposed mechanism of action is antiadhesion of bacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19284180", "endSection": "abstract" }, { "offsetInBeginSection": 1427, "offsetInEndSection": 1617, "text": "The AFM adhesion force measurements were consistent with the results of a hemagglutination assay, confirming that oral consumption of CJC could act against adhesion of uropathogenic E. coli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21480803", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 945, "text": "These data suggest that daily consumption of concentrated cranberry juice can significantly prevent the recurrence of symptomatic UTIs in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19921981", "endSection": "abstract" } ] }, { "body": "In which diseases have electronic patient diaries been applied ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20841643", "http://www.ncbi.nlm.nih.gov/pubmed/19301936", "http://www.ncbi.nlm.nih.gov/pubmed/22949085", "http://www.ncbi.nlm.nih.gov/pubmed/8904620", "http://www.ncbi.nlm.nih.gov/pubmed/10594395", "http://www.ncbi.nlm.nih.gov/pubmed/14728392", "http://www.ncbi.nlm.nih.gov/pubmed/19999626", "http://www.ncbi.nlm.nih.gov/pubmed/19226411" ], "ideal_answer": [ "Parkinson's disease\nCOPD\nFood hypersensitivity\nNiacin induced flushing\nHemophilia\nHeartburn\nHeadache" ], "exact_answer": [ [ "Parkinson's disease" ], [ "COPD", "Chronic obstructive pulmonary disease", "Chronic Obstructive Airways Disease", "Chronic Obstructive Lung Disease" ], [ "Food hypersensitivity", "Allergy" ], [ "Niacin induced flushing" ], [ "Hemophilia" ], [ "Heartburn", "Reflux", "GERD", "Esophageal reflux" ], [ "Headache", "Migraine", "migraine headache", "Migraine Disorder", "Migraine Headaches" ] ], "type": "list", "id": "550303a5e9bde6963400000c", "snippets": [ { "offsetInBeginSection": 124, "offsetInEndSection": 538, "text": "WiiPD is an approach for the objective home based assessment of Parkinson's disease which utilizes the intuitive and sensor rich Nintendo Wii Remote. Combined with an electronic patient diary, a suite of mini-games, a metric analyzer, and a visualization engine, we propose that this system can complement existing clinical practice by providing objective metrics gathered frequently over extended periods of time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22949085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "This research paper examines the challenges in the development and adoption of an electronic patient diary within the Pathways Home for Respiratory Illness Project", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20841643", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 418, "text": "This project supported community-based patients suffering from chronic obstructive pulmonary disease (COPD) to achieve increased levels of self-management and self-efficacy using electronic-monitoring techniques and mentoring by community health nurses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20841643", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 836, "text": "Instead of measuring physiological parameters, a Smartphone based Personal Allergy Assistant (PAA) allows patients to keep an electronic patient diary by scanning the barcode of the consumed food products.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19999626", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 77, "text": "Telemedicine assisted diet and diagnosis management in food hypersensitivity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19999626", "endSection": "title" }, { "offsetInBeginSection": 147, "offsetInEndSection": 279, "text": "The Flushing ASsessment Tool (FAST) was developed to assess flushing symptoms and their impact on patients receiving niacin therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19301936", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 675, "text": " This was a prospective, randomized, double-blind, placebo-controlled, parallel-group 8-week study conducted to evaluate the psychometric characteristics of the FAST. The instrument is administered daily using an electronic patient diary.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19301936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Haemoassist--a hand-held electronic patient diary for haemophilia home care.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19226411", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "A comparison of self-documentation in diabetics: electronic versus paper diaries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14728392", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 548, "text": "Subjects with self-perceived heartburn without known gastrointestinal disease or interfering treatments were selected with questionnaires. The study was performed unsupervised, whenever heartburn required medication. An electronic patient diary gave instructions when to take study medication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10594395", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Self-medication of a single headache episode with ketoprofen, ibuprofen or placebo, home-monitored with an electronic patient diary.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8904620", "endSection": "title" } ] }, { "body": "Which type of myeloma is ixazomib being evaluated for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24920586", "http://www.ncbi.nlm.nih.gov/pubmed/24292417", "http://www.ncbi.nlm.nih.gov/pubmed/24904120", "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "http://www.ncbi.nlm.nih.gov/pubmed/25268212", "http://www.ncbi.nlm.nih.gov/pubmed/24486586", "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "http://www.ncbi.nlm.nih.gov/pubmed/24578203", "http://www.ncbi.nlm.nih.gov/pubmed/25456369", "http://www.ncbi.nlm.nih.gov/pubmed/25302026", "http://www.ncbi.nlm.nih.gov/pubmed/25935605" ], "ideal_answer": [ "The disease focus for the irreversible epoxyketone proteasome inhibitor ixazomib is multiple myeloma." ], "exact_answer": [ "Multiple myeloma" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009101" ], "type": "factoid", "id": "56ed0ffe2ac5ed1459000008", "snippets": [ { "offsetInBeginSection": 353, "offsetInEndSection": 707, "text": "Next generation proteasome inhibitors include carfilzomib and oprozomib which are irreversible epoxyketone proteasome inhibitors; and ixazomib and delanzomib which are reversible boronic acid proteasome inhibitors. Two proteasome inhibitors, bortezomib and carfilzomib are FDA approved drugs and ixazomib and oprozomib are in late stage clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25935605", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 820, "text": "The disease focus for all the proteasome inhibitors is multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25935605", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1071, "text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "endSection": "abstract" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1454, "text": "These findings have informed the subsequent clinical development of ixazomib in multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920586", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25302026", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904120", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "(18)F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292417", "endSection": "title" }, { "offsetInBeginSection": 506, "offsetInEndSection": 750, "text": "Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904120", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 508, "text": "Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904120", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 675, "text": "Among second-generation proteasome inhibitors, ixazomib (MLN9708) is the first oral compound to be evaluated for the treatment of MM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25302026", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 510, "text": "Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 396, "text": "Ixazomib is the first investigational oral proteasome inhibitor to be studied clinically. In this phase 1 trial, 60 patients with relapsed/refractory multiple myeloma (median of 4 prior lines of therapy; bortezomib, lenalidomide, thalidomide, and carfilzomib/marizomib in 88%, 88%, 62%, and 5%, respectively) received single-agent ixazomib 0.24 to 2.23 mg/m(2) (days 1, 4, 8, 11; 21-day cycles). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25456369", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 892, "text": "In a phase 1/2 trial we aimed to assess the safety, tolerability, and activity of ixazomib in combination with lenalidomide and dexamethasone in newly diagnosed multiple myeloma.METHODS: We enrolled patients newly diagnosed with multiple myeloma aged 18 years or older with measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and no grade 2 or higher peripheral neuropathy, and treated them with oral ixazomib (days 1, 8, 15) plus lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (days 1, 8, 15, 22) for up to 12 28-day cycles, followed by maintenance therapy with ixazomib alone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25456369", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 872, "text": "Among second-generation proteasome inhibitors, ixazomib (MLN9708) is the first oral compound to be evaluated for the treatment of MM. Ixazomib has shown improved pharmacokinetic and pharmacodynamic parameters compared with bortezomib, in addition to similar efficacy in the control of myeloma growth and prevention of bone loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25302026", "endSection": "abstract" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1368, "text": "Among 55 response-evaluable patients, 15% achieved partial response or better (76% stable disease or better). These findings have informed the subsequent clinical development of ixazomib in multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920586", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 510, "text": "Ixazomib is an investigational, orally bioavailable 20S proteasome inhibitor. Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904120", "endSection": "abstract" } ] }, { "body": "Which are the Atg8 homologs in human?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21893048", "http://www.ncbi.nlm.nih.gov/pubmed/23043107", "http://www.ncbi.nlm.nih.gov/pubmed/20418806", "http://www.ncbi.nlm.nih.gov/pubmed/21862879", "http://www.ncbi.nlm.nih.gov/pubmed/20723759", "http://www.ncbi.nlm.nih.gov/pubmed/22948227", "http://www.ncbi.nlm.nih.gov/pubmed/10856287", "http://www.ncbi.nlm.nih.gov/pubmed/16303767", "http://www.ncbi.nlm.nih.gov/pubmed/22120110", "http://www.ncbi.nlm.nih.gov/pubmed/20562859", "http://www.ncbi.nlm.nih.gov/pubmed/22302004", "http://www.ncbi.nlm.nih.gov/pubmed/20574168", "http://www.ncbi.nlm.nih.gov/pubmed/19549685", "http://www.ncbi.nlm.nih.gov/pubmed/21620860", "http://www.ncbi.nlm.nih.gov/pubmed/23022382" ], "ideal_answer": [ "Autophagy (Autophagy-related protein 8 or Atg8p or APG8 or AUT7 or CVT5) is a yeast protein involved in cytoplasm to vacuole transport (Cvt) vesicles and autophagosomes formation. In yeast it is represented by a single gene, the ATG8 family in humans contains 6 members (microtubule-associated protein-1 light chain 3A (MAP1LC3A), MAP1LC3B, MAP1LC3C, GABA(A) receptor-associated protein (GABARAP), GABARAPL1, and GABARAPL2/GATE-16)." ], "exact_answer": [ [ "MAP1LC3A", "microtubule-associated protein-1 light chain 3A", "LC3A" ], [ "MAP1LC3B", "microtubule-associated protein-1 light chain 3B", "LC3B" ], [ "MAP1LC3C", "microtubule-associated protein-1 light chain 3C", "LC3C" ], [ "GABARAP", "GABA(A) receptor-associated protein", "Gamma-aminobutyric acid receptor-associated protein", "MM46" ], [ "GABARAPL1", "Gamma-aminobutyric acid receptor-associated protein-like 1", "Early estrogen-regulated protein", "GABA(A) receptor-associated protein-like 1", "Glandular epithelial cell protein 1", "GEC-1" ], [ "GABARAPL2", "Gamma-aminobutyric acid receptor-associated protein-like 2", "GABA(A) receptor-associated protein-like 2", "Ganglioside expression factor 2", "GEF-2", "General protein transport factor p16", "Golgi-associated ATPase enhancer of 16 kDa", "GATE-16", "MAP1 light chain 3-related protein" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.uniprot.org/uniprot/ATG8_MAGO7" ], "type": "list", "id": "51bdf045047fa84d1d000003", "snippets": [ { "offsetInBeginSection": 482, "offsetInEndSection": 631, "text": "Strikingly, in addition to ULK1 and ULK2, ATG13 and FIP200 interacted with human ATG8 proteins, all with strong preference for the GABARAP subfamily.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23043107", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "GABARAPL1 belongs to the small family of GABARAP proteins (including GABARAP, GABARAPL1 and GABARAPL2/GATE-16), one of the two subfamilies of the yeast Atg8 orthologue.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120110", "endSection": "sections.0" }, { "offsetInBeginSection": 76, "offsetInEndSection": 182, "text": "Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893048", "endSection": "title" }, { "offsetInBeginSection": 398, "offsetInEndSection": 505, "text": "Stbd1 has been reported to interact with a known autophagy protein, GABARAPL1, a member of the Atg8 family.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893048", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 424, "text": "Atg8 is a yeast protein involved in the autophagic process and in particular in the elongation of autophagosomes. In mammals, several orthologs have been identified and are classed into two subfamilies: the LC3 subfamily and the GABARAP subfamily, referred to simply as the LC3 or GABARAP families. GABARAPL1 (GABARAP-like protein 1), one of the proteins belonging to the GABARAP (GABA(A) receptor-associated protein) family", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862879", "endSection": "sections.0" }, { "offsetInBeginSection": 565, "offsetInEndSection": 776, "text": "The proteins that make up the GABARAP family demonstrate conservation of their amino acid sequences and protein structures. In humans, GABARAPL1 shares 86% identity with GABARAP and 61% with GABARAPL2 (GATE-16).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862879", "endSection": "sections.0" }, { "offsetInBeginSection": 96, "offsetInEndSection": 311, "text": "The selectivity is mediated by autophagy receptors, such as p62 and NBR1, which can bind to autophagic effector proteins (Atg8 in yeast, MAP1LC3 protein family in mammals) anchored in the membrane of autophagosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21620860", "endSection": "sections.0" }, { "offsetInBeginSection": 204, "offsetInEndSection": 282, "text": "ATG3 is the E2-like enzyme necessary for ATG8/LC3 lipidation during autophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20723759", "endSection": "sections.0" }, { "offsetInBeginSection": 154, "offsetInEndSection": 356, "text": "Recently, autophagy receptors, like p62/SQSTM1 and NBR1, which physically link autophagic cargo to ATG8/MAP1-LC3/GABARAP family members located on the forming autophagic membranes, have been identified.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20574168", "endSection": "sections.0" }, { "offsetInBeginSection": 173, "offsetInEndSection": 361, "text": "At least eight different Atg8 orthologs belonging to two subfamilies (LC3 and GATE-16/GABARAP) occur in mammalian cells, but their individual roles and modes of action are largely unknown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20418806", "endSection": "sections.0" }, { "offsetInBeginSection": 589, "offsetInEndSection": 741, "text": "truncated DeltaN63 Atg4D displays increased activity against the Atg8 paralogue, gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAP-L1)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549685", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10856287", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 300, "text": "The yeast ortholog of GATE-16 is the autophagocytosis factor Aut7p. GATE-16 is also closely related to the GABA receptor-associated protein (GABARAP),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10856287", "endSection": "sections.0" }, { "offsetInBeginSection": 126, "offsetInEndSection": 384, "text": "Three human Atg8 (hAtg8) homologs, LC3, GABARAP, and GATE-16, have been characterized as modifiers in reactions mediated by hAtg7 (an E1-like enzyme) and hAtg3 (an E2-like enzyme) as in yeast Atg8 lipidation, but their final targets have not been identified.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16303767", "endSection": "sections.0" } ] }, { "body": "To which family does the Zika virus belong?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25310102" ], "triples": [ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/taxonomy/64320", "o": "false" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/64320", "o": "Zika virus" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0820708", "o": "64320" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0820708", "o": "Zika virus" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14224049", "o": "Zika virus (organism)" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0318793", "o": "http://linkedlifedata.com/resource/umls/label/A0820708" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0318793", "o": "http://linkedlifedata.com/resource/umls/label/A14224049" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0820708", "o": "NCBI Taxonomy" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14224049", "o": "Metathesaurus Names" } ], "ideal_answer": [ "The Zika virus belongs to the family Flaviviridae." ], "exact_answer": [ "Flaviviridae" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009679", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014780", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014777", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005190" ], "type": "factoid", "id": "56b76d916e3f8eaf4c000001", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 69, "text": "Zika virus (ZIKV; genus Flavivirus, family Flaviviridae) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25310102", "endSection": "abstract" } ] }, { "body": "Has the fungus Ashbya gossypii got many nuclei that share cytoplasm?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24094857", "http://www.ncbi.nlm.nih.gov/pubmed/20053682", "http://www.ncbi.nlm.nih.gov/pubmed/16449188", "http://www.ncbi.nlm.nih.gov/pubmed/16023404", "http://www.ncbi.nlm.nih.gov/pubmed/17158735", "http://www.ncbi.nlm.nih.gov/pubmed/23015595", "http://www.ncbi.nlm.nih.gov/pubmed/21737675", "http://www.ncbi.nlm.nih.gov/pubmed/21642510", "http://www.ncbi.nlm.nih.gov/pubmed/16899511", "http://www.ncbi.nlm.nih.gov/pubmed/22267774", "http://www.ncbi.nlm.nih.gov/pubmed/20844079", "http://www.ncbi.nlm.nih.gov/pubmed/11181180", "http://www.ncbi.nlm.nih.gov/pubmed/17122387", "http://www.ncbi.nlm.nih.gov/pubmed/19910487", "http://www.ncbi.nlm.nih.gov/pubmed/23771903" ], "ideal_answer": [ "Yes, Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002467", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002529" ], "type": "yesno", "id": "550e6688a103b7801600000d", "snippets": [ { "offsetInBeginSection": 81, "offsetInEndSection": 118, "text": "multinucleated Ashbya gossypii cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158735", "endSection": "title" }, { "offsetInBeginSection": 60, "offsetInEndSection": 103, "text": "multinucleated Ashbya gossypii fungal cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17122387", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide asynchronously. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16899511", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 108, "text": "multinucleated Ashbya gossypii cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16899511", "endSection": "title" }, { "offsetInBeginSection": 55, "offsetInEndSection": 168, "text": "We analyzed a unique asynchronous nuclear division cycle in a multinucleated filamentous fungus, Ashbya gossypii.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16449188", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 103, "text": " multinucleated hyphae in Ashbya gossypii.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16023404", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "We have followed the migration of GFP-labelled nuclei in multinucleate hyphae of Ashbya gossypii", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11181180", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 319, "text": "multinucleate fungus Ashbya gossypii", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24094857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Ashbya gossypii grows as multinucleated and constantly elongating hyphae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23771903", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 96, "text": "multinucleated hyphae of Ashbya gossypii.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015595", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "We report the mechanistic basis guiding the migration pattern of multiple nuclei in hyphae of Ashbya gossypii. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015595", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 139, "text": "multinucleate fungal cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22267774", "endSection": "title" }, { "offsetInBeginSection": 35, "offsetInEndSection": 107, "text": "multinucleate Ashbya gossypii cells relies on a minimal network of genes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737675", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Clustering of nuclei in multinucleated hyphae is prevented by dynein-driven bidirectional nuclear movements and microtubule growth control in Ashbya gossypii.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642510", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs) emerge from the spindle pole body outer plaque (OP) in perpendicular and tangential directions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20053682", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 125, "text": "multinucleated hyphae of Ashbya gossypii.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19910487", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 53, "text": "multiple nuclei in Ashbya gossypii hyphae", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20844079", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20844079", "endSection": "abstract" } ] }, { "body": "What is the functionality of the Triplex R/bioconductor package?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23709494" ], "ideal_answer": [ "Triplex is an R/Bioconductor package for identification and visualization of potential intramolecular triplex patterns in DNA sequences. The package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz." ], "type": "summary", "id": "56d1ddd267f0cb3d66000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Triplex: an R/Bioconductor package for identification and visualization of potential intramolecular triplex patterns in DNA sequences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23709494", "endSection": "title" }, { "offsetInBeginSection": 258, "offsetInEndSection": 829, "text": "The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23709494", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 579, "text": "RESULTS: We combined a previously published implementation of a triplex DNA search algorithm with visualization to create a versatile R/Bioconductor package 'triplex'. The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23709494", "endSection": "abstract" } ] }, { "body": "Which is the molecular mechanism underlying K-ras alterations in carcinomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19509115", "http://www.ncbi.nlm.nih.gov/pubmed/12697967", "http://www.ncbi.nlm.nih.gov/pubmed/19783717", "http://www.ncbi.nlm.nih.gov/pubmed/8613066", "http://www.ncbi.nlm.nih.gov/pubmed/21779504", "http://www.ncbi.nlm.nih.gov/pubmed/8178941", "http://www.ncbi.nlm.nih.gov/pubmed/16757361", "http://www.ncbi.nlm.nih.gov/pubmed/16166322", "http://www.ncbi.nlm.nih.gov/pubmed/19826477", "http://www.ncbi.nlm.nih.gov/pubmed/21626008", "http://www.ncbi.nlm.nih.gov/pubmed/21886451" ], "ideal_answer": [ "Activating point mutations most frequently in codon 12" ], "exact_answer": [ "Point mutations" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011905", "http://www.disease-ontology.org/api/metadata/DOID:305", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0032856" ], "type": "factoid", "id": "5177def18ed59a060a000034", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 79, "text": "activating mutations in KRAS are identified in most pancreatic cancers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16757361", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 182, "text": "Mutations at codon 12 of the K-ras gene are present in 65%-100% of carcinomas of human exocrine pancreas and could be used as a potential tumor marker at the tissue level.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8613066", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Activating point mutations in the K-Ras oncogene are among the most common genetic alterations in pancreatic cancer, occurring early in the progression of the disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509115", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Activating K-ras mutations are found in approximately 90% of pancreatic carcinomas and may contribute to the poor prognosis of these tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16166322", "endSection": "sections.0" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1216, "text": "Five of the seven duct lesions harbored activating point mutations in codon 12 of K-ras; a G to A transition was found in four and a G to C transversion in one.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8178941", "endSection": "sections.0" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1095, "text": "Ki-RAS mutations in 38% of the overall series", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12697967", "endSection": "sections.0" }, { "offsetInBeginSection": 533, "offsetInEndSection": 665, "text": "KRAS exon 2 mutations were detected in a total of 62 patients with the two methods combined, comprising 11 different mutant alleles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19783717", "endSection": "sections.0" }, { "offsetInBeginSection": 9, "offsetInEndSection": 119, "text": "gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21779504", "endSection": "sections.0" } ] }, { "body": "Is microRNA(miRNA) 30 involved in post-ischemic cardiac remodeling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22352753", "http://www.ncbi.nlm.nih.gov/pubmed/21434842", "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "http://www.ncbi.nlm.nih.gov/pubmed/19096030" ], "ideal_answer": [ "Myocardial remodeling after an ischemic insult involves extracellular matrix proteins with increased fibrosis\nInitial experimental data indicate that miRNA 30 decreases CTGF a key molecule in the process of fibrosis, by directly downregulating the production of CTGF" ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010586", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "yesno", "id": "513f4249bee46bd34c000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosi", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096030", "endSection": "sections.0" }, { "offsetInBeginSection": 209, "offsetInEndSection": 345, "text": "Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an attractive therapeutic target", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096030", "endSection": "sections.0" }, { "offsetInBeginSection": 571, "offsetInEndSection": 659, "text": "CTGF is importantly regulated by 2 major cardiac microRNAs (miRNAs), miR-133 and miR-30.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096030", "endSection": "sections.0" }, { "offsetInBeginSection": 667, "offsetInEndSection": 1060, "text": "the expression of both miRNAs was inversely related to the amount of CTGF in 2 rodent models of heart disease and in human pathological left ventricular hypertrophy. Second, in cultured cardiomyocytes and fibroblasts, knockdown of these miRNAs increased CTGF levels. Third, overexpression of miR-133 or miR-30c decreased CTGF levels, which was accompanied by decreased production of collagens.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096030", "endSection": "sections.0" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1296, "text": "miR-30 importantly limit the production of CTGF", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096030", "endSection": "sections.0" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1733, "text": "miR-30 directly downregulate CTGF, a key profibrotic protein, and thereby establish an important role for these miRNAs in the control of structural changes in the extracellular matrix of the myocardium.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096030", "endSection": "sections.0" } ] }, { "body": "List all clinical trials of the polypill.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15670547", "http://www.ncbi.nlm.nih.gov/pubmed/21682553", "http://www.ncbi.nlm.nih.gov/pubmed/22080542", "http://www.ncbi.nlm.nih.gov/pubmed/20334446", "http://www.ncbi.nlm.nih.gov/pubmed/16479100", "http://www.ncbi.nlm.nih.gov/pubmed/15830173", "http://www.ncbi.nlm.nih.gov/pubmed/22787067", "http://www.ncbi.nlm.nih.gov/pubmed/19339045", "http://www.ncbi.nlm.nih.gov/pubmed/21205325", "http://www.ncbi.nlm.nih.gov/pubmed/21777702", "http://www.ncbi.nlm.nih.gov/pubmed/20687931", "http://www.ncbi.nlm.nih.gov/pubmed/21647425", "http://www.ncbi.nlm.nih.gov/pubmed/23038750", "http://www.ncbi.nlm.nih.gov/pubmed/18227490", "http://www.ncbi.nlm.nih.gov/pubmed/22162939" ], "ideal_answer": [ "'Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial, European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250.\n'IMProving Adherence using Combination Therapy (IMPACT)', Australian New Zealand Clinical Trial Registry (ACTRN12606000067572).\n'Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)'\nPhase II study of the Polycap, double-blind, randomised trial, registered with ClinicalTrials.gov, number NCT00443794\nSecond Indian Polycap Study, TIPS-2\nCluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial)\nGEMINI trial, 14-week, open-label trial conducted in 1220 patients from the USA\nGEMINI-Australia, Asia, Latin America, Africa/Middle East (AALA) study \nJEWEL study program, with JEWEL 1 conducted among 1138 patients from the UK and Canada and JEWEL 2 conducted in 1107 patients from Europe\nCAPABLE54, the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points , in the USA\nCUSP (The Caduet\u00ae in an Untreated Subject Population trial)\nTOGETHER trial\nA randomised controlled trial in seven countries \u2013 Australia, Brazil, India, Netherlands , New Zealand , United Kingdom and United States. Australian New Zealand Clinical Trials Registry (ACTRN 12607000099426)", "A number of clinical trials evaluating polypill, mainly in cardiovascular patients, have been performed and include the Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial, Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial), Atorvastatin and Amlodipine in Patients with Elevated Lipids and Hypertension (AVALON) trial, Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), GEMINI trial, GEMINI-Australia, Asia, Latin America, Africa/Middle East (GEMINI-AALA) study, JEWEL 1 trial, JEWEL 2 trial, Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points (CAPABLE54), The Caduet\u00ae in an Untreated Subject Population trial (CUSP), TOGETHER trial, TIPS trial, TIPS-2 trial and IMProving Adherence using Combination Therapy (IMPACT)." ], "exact_answer": [ [ "Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial, European Clinical Trials database\\, as EudraCT: 2009-016278-34 and the Clinical Trials Registry\\, India as CTRI/2010/091/000250.", "UMPIRE" ], [ "IMProving Adherence using Combination Therapy (IMPACT)', Australian New Zealand Clinical Trial Registry (ACTRN12606000067572)", "IMPACT" ], [ "Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)" ], [ "Phase II study of the Polycap, double-blind\\, randomised trial\\, registered with ClinicalTrials.gov\\, number NCT00443794", "ndian Polycap Study, TIPS", "TIPS" ], [ "Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial)", "CRUCIAL" ], [ "GEMINI trial, 14-week\\, open-label trial conducted in 1220 patients from the USA", "GEMINI" ], [ "GEMINI-Australia, Asia\\, Latin America\\, Africa/Middle East (AALA) study", "GEMINI-AALA" ], [ "JEWEL 1 conducted among 1138 patients from the UK and Canada", "JEWEL 1" ], [ "JEWEL 2 conducted in 1107 patients from Europe", "JEWEL 2" ], [ "CAPABLE54, the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points\\, in the USA", "CAPABLE54" ], [ "CUSP (The Caduet\u00ae in an Untreated Subject Population trial)", "CUSP" ], [ "TOGETHER trial", "TOGETHER" ], [ "A randomised controlled trial in seven countries \u2013 Australia, Brazil\\, India\\, Netherlands\\, New Zealand\\, United Kingdom and United States\\, Australian New Zealand Clinical Trials Registry (ACTRN 12607000099426)" ], [ "Second Indian Polycap Study, TIPS-2", "TIPS-2" ], [ " Atorvastatin and Amlodipine in Patients with Elevated Lipids and Hypertension (AVALON) trial", "AVALON" ], [ "Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)", "ASCOT" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986" ], "type": "list", "id": "515db020298dcd4e51000011", "snippets": [ { "offsetInBeginSection": 404, "offsetInEndSection": 987, "text": "The 'Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial assesses whether a polypill strategy (by combining aspirin, a statin and two blood pressure lowering agents) would improve adherence to guideline-indicated therapies and would lower both blood pressure and cholesterol, in people with established cardiovascular disease. UMPIRE, running in India and three European countries (England, Ireland and the Netherlands), is an open, randomised, controlled trial designed to include 1000 participants in India and 1000 in Europe, with a followup of 12-24 months.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23038750", "endSection": "sections.0" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1923, "text": "UMPIRE is registered with the European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250. The trial was part of the 'Single Pill Against Cardiovascular Events (SPACE)' collaboration, which encompasses the 'IMProving Adherence using Combination Therapy (IMPACT)' and 'Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)' trials.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23038750", "endSection": "sections.0" }, { "offsetInBeginSection": 711, "offsetInEndSection": 897, "text": "IMProving Adherence using Combination Therapy (IMPACT) is an open-label randomised controlled trial comparing a once-daily polypill containing four preventive medications with usual care", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21777702", "endSection": "sections.0" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1803, "text": "The trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12606000067572).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21777702", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339045", "endSection": "title" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1352, "text": "This study is registered with ClinicalTrials.gov, number NCT00443794", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339045", "endSection": "sections.0" } ] }, { "body": "What is transvection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12429702", "http://www.ncbi.nlm.nih.gov/pubmed/2238088", "http://www.ncbi.nlm.nih.gov/pubmed/3135240", "http://www.ncbi.nlm.nih.gov/pubmed/9348657", "http://www.ncbi.nlm.nih.gov/pubmed/11931232", "http://www.ncbi.nlm.nih.gov/pubmed/11504843", "http://www.ncbi.nlm.nih.gov/pubmed/10322135", "http://www.ncbi.nlm.nih.gov/pubmed/1979484", "http://www.ncbi.nlm.nih.gov/pubmed/2505416" ], "ideal_answer": [ "An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals.", "Pairing-dependent interallelic complementation was first described for the Ultrabithorax gene of the bithorax-complex in Drosophila by Lewis and cited as an example of a new phenomenon that Lewis called the trans-vection effect. Several different kinds of pairing-dependent gene expression have been observed in Drosophila, and it is now clear that a variety of different molecular mechanisms probably underlie the changes in gene expression that are observed after disrupting chromosome pairing. Transvection in the bithorax-complex appears to result from the ability of cis-regulatory elements to regulate transcription of the promoter on the homologous chromosome. The same phenomenon appears to be responsible for pairing-dependent interallelic complementation at numerous other genes in Drosophila. Some transvection effects are dependent on the presence of wild-type or specific mutant forms of the protein encoded by the zeste trans-regulatory gene, but other transvection effects are zeste-independent. The ease with which chromosome aberrations can disrupt transvection also varies widely among different genes " ], "type": "summary", "id": "553d0c1df321868558000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1604, "text": "An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12429702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1121, "text": "Pairing-dependent interallelic complementation was first described for the Ultrabithorax gene of the bithorax-complex in Drosophila by Lewis and cited as an example of a new phenomenon that Lewis called the \"trans-vection effect.\" Several different kinds of pairing-dependent gene expression have been observed in Drosophila, and it is now clear that a variety of different molecular mechanisms probably underlie the changes in gene expression that are observed after disrupting chromosome pairing. Transvection in the bithorax-complex appears to result from the ability of cis-regulatory elements to regulate transcription of the promoter on the homologous chromosome. The same phenomenon appears to be responsible for pairing-dependent interallelic complementation at numerous other genes in Drosophila. Some transvection effects are dependent on the presence of wild-type or specific mutant forms of the protein encoded by the zeste trans-regulatory gene, but other transvection effects are zeste-independent. The ease with which chromosome aberrations can disrupt transvection also varies widely among different genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11931232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "The presence of homologous nucleic acid sequences can exert profound effects on chromosomal and gene function in a wide range of organisms. These homology effects reveal remarkable forms of regulation as well as suggest possible avenues for the development of new technologies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10322135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 667, "text": "Enhancers have been defined operationally as cis-regulatory sequences that can stimulate transcription of RNA polymerase-II-transcribed genes over large distances and even when located downstream of the gene. Recently, it has become evident that enhancers can also stimulate transcription in trans if they are brought into close proximity to the promoter/gene. These reports provide clues to the mechanism of remote enhancer action. In addition, the findings, together with genetic studies in Drosophila, strongly suggest that enhancer action in trans could underlie phenomena such as 'transvection', where one chromosome affects gene expression in the paired homolog", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2238088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 559, "text": "Numerous genes contain regulatory elements located many tens of kilobases away from the promoter they control. Specific mechanisms must be required to ensure that such distant elements can find and interact with their proper targets but not with extraneous genes. This review explores the connections between transvection phenomena, the activation of domains of homeotic gene expression, position effect variegation and silencers. These various examples of long-distance effects suggest that, in all cases, related forms of chromatin packaging may be involved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1979484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "The zeste locus of Drosophila melanogaster encodes a DNA-binding protein that can influence transcription. A number of sites recognized by this protein fall within genes associated with transvection, a phenomenon suggesting a form of gene regulation that is responsive to the proximity of a gene to its homologous allele on another chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2505416", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 412, "text": "Special attention is paid to the transvection effect (synapsis-dependent interaction between white and zeste genes), cis-acting regulatory elements and the behaviour of the white genes introduced into the genome by P element-mediated DNA transformation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3135240", "endSection": "abstract" } ] }, { "body": "What is the role of probiotics in gastrointestinal disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15076628", "http://www.ncbi.nlm.nih.gov/pubmed/12846937", "http://www.ncbi.nlm.nih.gov/pubmed/16215086", "http://www.ncbi.nlm.nih.gov/pubmed/20890386", "http://www.ncbi.nlm.nih.gov/pubmed/21426607", "http://www.ncbi.nlm.nih.gov/pubmed/22529959", "http://www.ncbi.nlm.nih.gov/pubmed/19930635", "http://www.ncbi.nlm.nih.gov/pubmed/22118700", "http://www.ncbi.nlm.nih.gov/pubmed/20216432" ], "ideal_answer": [ "Probiotics are live, microbial food supplements that benefit the host animal by improving intestinal microbial balance. Across all 11 probiotic species and eight different gastrointestinal diseases - Irritable Bowel Syndrome (IBS), Helicobacter pylori infection (HPP), Necrotizing Enterocolitis (NEC), Pouchitis (Pouch), Antibiotic Associated diarrhea (AAD), Clostridium difficile Disease (CDD), Infectious diarrhea (ID), and Travellers diarrhea (TD) - probiotics have been shown to have effect on prevention and treatment of gastrointestinal disease through enhancing the immune response, protection against abnormal invasive bacteria. Probiotics have a role in all age groups, incl. infants." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005767", "http://www.disease-ontology.org/api/metadata/DOID:77", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019936" ], "type": "summary", "id": "515de643298dcd4e51000022", "snippets": [ { "offsetInBeginSection": 619, "offsetInEndSection": 1210, "text": "The overall response rate was 80.5%, of which 69.5% of respondents said they recommended or prescribed probiotic food supplements to their patients, including 53.4% of surgeons and 80.8% of gastroenterologists (P = 0.00013). The most popular probiotic supplements among surgeons were probiotic-containing yoghurt and drinks (79.5% and 71.8%, respectively), whereas VSL#3 was more popular with gastroenterologists (83.3%). The most popular indications were irritable bowel syndrome (70.7% of prescribers) and pouchitis (67.5% of prescribers). Many respondents prescribed long-term probiotics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22118700", "endSection": "sections.0" }, { "offsetInBeginSection": 266, "offsetInEndSection": 776, "text": "Current evidence indicates that probiotic effects are strain-specific, they do not act through the same mechanisms, and nor are all probiotics indicated for the same health conditions. However, they do share several common features in that they exert anti-inflammatory effects, they employ different strategies to antagonize competing microorganisms, and they induce cytoprotective changes in the host either through enhancement of barrier function, or through the upregulation of cytoprotective host proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20890386", "endSection": "sections.0" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1360, "text": "Most surveyed physicians recommended probiotics for irritable bowel syndrome, antibiotic, and Clostridium difficile-associated diarrhea because they believed that the literature supports their usage for these conditions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20216432", "endSection": "sections.0" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1681, "text": "This study suggests most gastrointestinal disease specialists recognize a role for and have used probiotics as part of their therapeutic armamentarium", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20216432", "endSection": "sections.0" }, { "offsetInBeginSection": 242, "offsetInEndSection": 363, "text": "probiotics for these patients with small bowel bacterial overgrowth, inflammatory bowel disease, and radiation enteritis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16215086", "endSection": "sections.0" }, { "offsetInBeginSection": 1764, "offsetInEndSection": 1957, "text": "These results provide some evidence that viable Bifidobacterium lactis strain Bb 12, added to an acidified infant formula, has some protective effect against acute diarrhea in healthy children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15076628", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "Probiotics are live, microbial food supplements that benefit the host animal by improving intestinal microbial balance. Their major role in preventing and treating gastrointestinal disease appears to be from their effect on the immune process, protection against abnormal invasive bacteria, and in the production of short-chain fatty acids from starch and non-starch polysaccharides.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12846937", "endSection": "sections.0" } ] }, { "body": "What is the main symptom of Marfan syndrome patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23801775", "http://www.ncbi.nlm.nih.gov/pubmed/25490352", "http://www.ncbi.nlm.nih.gov/pubmed/24721296", "http://www.ncbi.nlm.nih.gov/pubmed/23877552", "http://www.ncbi.nlm.nih.gov/pubmed/1464550", "http://www.ncbi.nlm.nih.gov/pubmed/21958999", "http://www.ncbi.nlm.nih.gov/pubmed/10147800", "http://www.ncbi.nlm.nih.gov/pubmed/20067609", "http://www.ncbi.nlm.nih.gov/pubmed/3392569", "http://www.ncbi.nlm.nih.gov/pubmed/22397493", "http://www.ncbi.nlm.nih.gov/pubmed/23852405", "http://www.ncbi.nlm.nih.gov/pubmed/19216964", "http://www.ncbi.nlm.nih.gov/pubmed/16731131", "http://www.ncbi.nlm.nih.gov/pubmed/19430557", "http://www.ncbi.nlm.nih.gov/pubmed/23941798" ], "ideal_answer": [ "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. Pathohistological alterations of the aorta in patients with Marfan syndrome consisted in pronounced restructuring of the wall with deep irreversible alternative changes. The risk of aortic dissection, which is the most serious manifestation of the Marfan syndrome, increases as the aorta enlarges. Surgical replacement of the aortic root with a composite graft does not end the disease process.", "Marfan syndrome is a multisystemic connective tissue disorder caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular system is affected in patients with Marfan syndrome. Aortic root dilatation, which may involve the proximal and distal aorta, mitral valve prolapse, and mitral regurgitation, aortic valve regurgitation or - the most feared and life-threatening symptom - aortic root dissection are the most common manifestations.", "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. It is of utmost importance to identify patients at risk for acute aortic events to establish the correct surgical timing and the appropriate surgical treatment" ], "exact_answer": [ "aortic root dissection" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010361", "http://www.disease-ontology.org/api/metadata/DOID:14323", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382" ], "type": "factoid", "id": "56f4011709dd18d46b000003", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 263, "text": "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. It is of utmost importance to identify patients at risk for acute aortic events to establish the correct surgical timing and the appropriate surgical treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877552", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The not-uncommon spinal abnormalities associated with Marfan's syndrome rarely undergird clinical problems, and neurological features accompanying such bone abnormalities are rare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3392569", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 344, "text": "The major cardiovascular manifestations of this condition are aortic dilation, which may involve the proximal and distal aorta, aortic regurgitation, aortic dissection, mitral valve prolapse, and mitral regurgitation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10147800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "For the first time Bernhard Marfan described the Marfan-Syndrome in 1896; it is a meso- and ectodermed variety with the conducting symptom of \"arachnodactyly\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1464550", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 858, "text": "Initial physical examination revealed an aortic systolic murmur and musculoskeletal morphological abnormalities compatible with Marfan syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21958999", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 368, "text": "Marfan syndrome is a multisystemic connective tissue disorder caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular system is affected in patients with Marfan syndrome. Aortic root dilatation, aortic valve regurgitation or - the most feared and life-threatening symptom - aortic root dissection are the most common manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22397493", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 127, "text": "Meningeal abnormalities such as dural ectasia are seen in Marfan syndrome, but spinal meningeal cysts are rarely seen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23941798", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1483, "text": "Pathohistological alterations of the aorta in patients with Marfan syndrome consisted in pronounced restructuring of the wall with deep irreversible alternative changes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25490352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The characteristics of acute aortic dissection among young Chinese patients: a comparison between Marfan syndrome and non-Marfan syndrome patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19430557", "endSection": "title" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1029, "text": "The main objective of this trial is to assess whether losartan treatment leads to a clinically relevant decrease of aortic dilatation in adult patients with Marfan syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20067609", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 842, "text": "During a 16-year period, 300 patients with presumed Marfan syndrome underwent 398 operations on the aorta and branch arteries, including 125 aortic root operations, 59 aortic arch repairs, 31 descending thoracic aortic repairs, and 178 thoracoabdominal aortic repairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16731131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Aortic disease in patients with Marfan syndrome: aortic volume assessment for surveillance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23801775", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "To compare the clinical features of type A aortic dissection (AAD) in patients with Marfan syndrome (MFS) and bicuspid aortic valves (BAV)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24721296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23852405", "endSection": "title" } ] }, { "body": "What species is associated with Tetrodotoxin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22163191", "http://www.ncbi.nlm.nih.gov/pubmed/22069694", "http://www.ncbi.nlm.nih.gov/pubmed/20479966", "http://www.ncbi.nlm.nih.gov/pubmed/22690139", "http://www.ncbi.nlm.nih.gov/pubmed/23724281", "http://www.ncbi.nlm.nih.gov/pubmed/24279996", "http://www.ncbi.nlm.nih.gov/pubmed/24295175", "http://www.ncbi.nlm.nih.gov/pubmed/22028709", "http://www.ncbi.nlm.nih.gov/pubmed/20161971", "http://www.ncbi.nlm.nih.gov/pubmed/20637221", "http://www.ncbi.nlm.nih.gov/pubmed/20411115", "http://www.ncbi.nlm.nih.gov/pubmed/22688023", "http://www.ncbi.nlm.nih.gov/pubmed/21734837", "http://www.ncbi.nlm.nih.gov/pubmed/21549050" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0463937", "o": "DXplain" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0275142", "o": "http://linkedlifedata.com/resource/umls/label/A0463937" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0463937", "o": "TETRODOTOXIN POISONING" }, { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin", "o": "4368-28-9" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin", "o": "Tetrodotoxin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0366686", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0208311", "o": "http://linkedlifedata.com/resource/umls/label/A0366687" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0366686", "o": "Tetrodotoxin, (4beta)-" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0208311", "o": "http://linkedlifedata.com/resource/umls/label/A0366686" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0366687", "o": "4-epitetrodotoxin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0366687", "o": "MeSH" } ], "ideal_answer": [ "Tetrodotoxin (TTX) is a low molecular weight (approximately 319 Da) neurotoxin found in a number of animal species, including pufferfish. TTX is originally produced by marine bacteria, and pufferfish are intoxicated through the food chain that starts with the bacteria. TTX is found in warm waters, especially of the Indian and Pacific Oceans. TTX poisoning due to marine snails has recently spread through Japan, China, Taiwan, and Europe." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013779", "http://www.biosemantics.org/jochem#4053979", "http://www.biosemantics.org/jochem#4274648" ], "type": "summary", "id": "552033206b348bb82c00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The selling and importing of puffer fish species and their products was banned in Thailand in 2002, because of possible neurotoxic effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Efficiency of a rapid test for detection of tetrodotoxin in puffer fish.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295175", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Marine pufferfish contain tetrodotoxin (TTX), an extremely potent neurotoxin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24279996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Tetrodotoxin is a potent low weight marine toxin found in warm waters, especially of the Indian and Pacific Oceans. Intoxications are usually linked to the consumption of the puffer fish, although TTX was already detected in several different edible taxa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22690139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Food poisoning due to ingestion of a puffer fish occurred in Nagasaki Prefecture, Japan, in October 2008, causing neurotoxic symptoms similar to those of tetrodotoxin (TTX) poisoning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22688023", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1366, "text": " Our findings raised a concern for people, not only Thais but also inhabitants of other countries situated on the Andaman coast; consuming puffers of the Andaman seas is risky due to potential TTX intoxication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Toxic marine puffer fish in Thailand seas and tetrodotoxin they contained.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069694", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Puffer fish, Takifugu niphobles, collected from the Hong Kong coastal waters were screened for tetrodotoxin-producing bacteria. A Gram-negative, non-acid-fast, non-sporing and rod shaped bacterial strain (designated as gutB01) was isolated from the intestine of the puffer fish and was shown to produce tetrodotoxin (TTX)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22163191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Isolation and identification of a new tetrodotoxin-producing bacterial species, Raoultella terrigena, from Hong Kong marine puffer fish Takifugu niphobles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22163191", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Green toadfish Lagocephalus lunaris inhabits tropical and subtropical seas and contains high tetrodotoxin (TTX) levels in the muscle as well as liver and gonad", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Tetrodotoxin (TTX) is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Na(v))", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21734837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Suspected tetrodotoxin (TTX) poisoning was associated with eating unknown fish in April 2009 in Taiwan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Marine pufferfish generally contain a large amount of tetrodotoxin (TTX) in their skin and viscera, and have caused many incidences of food poisoning, especially in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724281", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 504, "text": " TTX is originally produced by marine bacteria, and pufferfish are intoxicated through the food chain that starts with the bacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724281", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 759, "text": ", TTX poisoning due to marine snails has recently spread through Japan, China, Taiwan, and Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The inhibitory effects of toxin extracted from muscle or liver of five different puffer fishes (hereafter referred as puffer(s)) captured on the Japanese sea coast ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20637221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "LC/MS analysis of tetrodotoxin and its deoxy analogs in the marine puffer fish Fugu niphobles from the southern coast of Korea, and in the brackishwater puffer fishes Tetraodon nigroviridis and Tetraodon biocellatus from Southeast Asia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479966", "endSection": "title" }, { "offsetInBeginSection": 200, "offsetInEndSection": 446, "text": "Toxins such as saxitoxins, tetrodotoxin, palytoxin, nodularin, okadaic acid, domoic acid, may be produced in large amounts by dinoflagellates, cyanobacteria, bacteria and diatoms and accumulate in vectors that transfer the toxin along food chains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20161971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Tetrodotoxin (TTX) is a low molecular weight (approximately 319 Da) neurotoxin found in a number of animal species, including pufferfish.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20411115", "endSection": "abstract" } ] }, { "body": "How is myotonic dystrophy inherited?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12970845", "http://www.ncbi.nlm.nih.gov/pubmed/18228241", "http://www.ncbi.nlm.nih.gov/pubmed/8154209", "http://www.ncbi.nlm.nih.gov/pubmed/22332444", "http://www.ncbi.nlm.nih.gov/pubmed/12577208" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1189440", "o": "myotonic dystrophy" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12058083", "o": "Myotonic Dystrophy" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0027126", "o": "http://linkedlifedata.com/resource/umls/label/A12058083" } ], "ideal_answer": [ "Myotonic dystrophy (DM) is a heterogeneous neuromuscular disease with an autosomal dominant pattern of inheritance." ], "exact_answer": [ "autosomal dominant" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11722", "http://www.disease-ontology.org/api/metadata/DOID:655", "http://www.disease-ontology.org/api/metadata/DOID:9884", "http://www.disease-ontology.org/api/metadata/DOID:450" ], "type": "factoid", "id": "51635202298dcd4e5100004f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 229, "text": "Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332444", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder, caused by an expansion of a CTG triplet repeat in the DMPK gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18228241", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, is a clinically and genetically heterogeneous neuromuscular disorder. DM is characterized by autosomal dominant inheritance, muscular dystrophy, myotonia, and multisystem involvement. Type 1 DM (DM1) is caused by a (CTG)(n) expansion in the 3' untranslated region of DMPK in 19q13.3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12970845", "endSection": "sections.0" }, { "offsetInBeginSection": 470, "offsetInEndSection": 677, "text": "proximal myotonic myopathy (PROMM) and type 2 DM (DM2) but without the DM1 mutation, showed linkage to the 3q21 region and were recently shown to segregate a (CCTG)(n) expansion mutation in intron 1 of ZNF9.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12970845", "endSection": "sections.0" }, { "offsetInBeginSection": 859, "offsetInEndSection": 905, "text": "All patients have the DM2 (CCTG)(n) expansion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12970845", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 195, "text": "Myotonic dystrophy type 1 is a neuromuscular, degenerative and progressive disease, with an autosomal dominant pattern of inheritance, variable expressivity and incomplete penetrance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12577208", "endSection": "sections.0" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1259, "text": "The worldwide intergenerational behavior of the DM1 mutation is similar in Costa Rica", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12577208", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Dystrophic myotonia is a sufficiently rare disease inherited mainly by the autosomal dominant type.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8154209", "endSection": "sections.0" } ] }, { "body": "How do HBS1L-MYB intergenic variants regulate fetal hemoglobin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24614105" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067026", "o": "D006454" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067106", "o": "D006454" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0058894", "o": "D005319" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067093", "o": "D005319" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067060", "o": "D005319" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067059", "o": "D005319" } ], "ideal_answer": [ "HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers. Several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. Several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels." ], "concepts": [ "http://www.biosemantics.org/jochem#4257620", "http://www.uniprot.org/uniprot/HBBF_CAPHI", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020570", "http://www.biosemantics.org/jochem#4256386", "http://www.uniprot.org/uniprot/MYB_BOVIN", "http://www.uniprot.org/uniprot/MYB_CHICK", "http://www.biosemantics.org/jochem#4265352", "http://www.biosemantics.org/jochem#4264315", "http://www.biosemantics.org/jochem#4249310", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020598", "http://www.uniprot.org/uniprot/MYB_HUMAN", "http://www.uniprot.org/uniprot/HBS1L_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006441", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006442", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006443", "http://www.biosemantics.org/jochem#4259159", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020626", "http://www.uniprot.org/uniprot/HBBF_BOVIN", "http://www.uniprot.org/uniprot/HBS1L_PONAB", "http://www.biosemantics.org/jochem#4249395", "http://amigo.geneontology.org/amigo/term/GO:0020027", "http://www.uniprot.org/uniprot/HBS1L_BOVIN", "http://amigo.geneontology.org/amigo/term/GO:0042540", "http://amigo.geneontology.org/amigo/term/GO:0031523", "http://amigo.geneontology.org/amigo/term/GO:0020028", "http://www.biosemantics.org/jochem#4264470", "http://www.biosemantics.org/jochem#4259595", "http://www.uniprot.org/uniprot/HBBF_SHEEP", "http://www.biosemantics.org/jochem#4256471", "http://www.uniprot.org/uniprot/HBB1_TRICR", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005319", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006454" ], "type": "summary", "id": "56ae5a8a0a360a5e4500000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24614105", "endSection": "title" }, { "offsetInBeginSection": 413, "offsetInEndSection": 1129, "text": "Here, we determined that several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. We found that several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels. These data provide a functional explanation for the genetic association of HBS1L-MYB intergenic polymorphisms with human erythroid traits and HbF levels. Our results further designate MYB as a target for therapeutic induction of HbF to ameliorate sickle cell and \u03b2-thalassemia disease severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24614105", "endSection": "abstract" } ] }, { "body": "Which are the mammalian orthologs of Drosophila Yki?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17980593", "http://www.ncbi.nlm.nih.gov/pubmed/18413746", "http://www.ncbi.nlm.nih.gov/pubmed/23484853", "http://www.ncbi.nlm.nih.gov/pubmed/22898666", "http://www.ncbi.nlm.nih.gov/pubmed/23985272", "http://www.ncbi.nlm.nih.gov/pubmed/22101275", "http://www.ncbi.nlm.nih.gov/pubmed/19878874" ], "ideal_answer": [ "There are two mammalian orthologs of Yki: YAP and TAZ" ], "exact_answer": [ [ "YAP" ], [ "TAZ" ] ], "concepts": [ "http://www.uniprot.org/uniprot/YORKI_DROME" ], "type": "list", "id": "533c2a55c45e133714000003", "snippets": [ { "offsetInBeginSection": 1508, "offsetInEndSection": 1527, "text": "Yorkie ortholog YAP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22898666", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 350, "text": "Yorkie ortholog, Yap1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19878874", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 284, "text": "human ortholog of Yorkie, YAP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18413746", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 251, "text": "YAP1, the ortholog of Drosophila Yorkie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980593", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 702, "text": "Yorkie ortholog YAP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23985272", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 710, "text": " Yorkie homolog YAP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23484853", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 936, "text": "Yki (YAP/TAZ in vertebrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22101275", "endSection": "abstract" } ] }, { "body": "Is statin use associated with improved outcomes after aneurysmal subarachnoid hemorrhage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16051891", "http://www.ncbi.nlm.nih.gov/pubmed/19875741", "http://www.ncbi.nlm.nih.gov/pubmed/19614959", "http://www.ncbi.nlm.nih.gov/pubmed/24323051", "http://www.ncbi.nlm.nih.gov/pubmed/19439205", "http://www.ncbi.nlm.nih.gov/pubmed/23392270", "http://www.ncbi.nlm.nih.gov/pubmed/20934152", "http://www.ncbi.nlm.nih.gov/pubmed/19458605", "http://www.ncbi.nlm.nih.gov/pubmed/16049199", "http://www.ncbi.nlm.nih.gov/pubmed/22709377", "http://www.ncbi.nlm.nih.gov/pubmed/23298376", "http://www.ncbi.nlm.nih.gov/pubmed/19199459", "http://www.ncbi.nlm.nih.gov/pubmed/19231192", "http://www.ncbi.nlm.nih.gov/pubmed/23633351", "http://www.ncbi.nlm.nih.gov/pubmed/19912325", "http://www.ncbi.nlm.nih.gov/pubmed/18382320", "http://www.ncbi.nlm.nih.gov/pubmed/18658040", "http://www.ncbi.nlm.nih.gov/pubmed/23691312", "http://www.ncbi.nlm.nih.gov/pubmed/22929438", "http://www.ncbi.nlm.nih.gov/pubmed/17413047", "http://www.ncbi.nlm.nih.gov/pubmed/17029334", "http://www.ncbi.nlm.nih.gov/pubmed/21125471", "http://www.ncbi.nlm.nih.gov/pubmed/21926584", "http://www.ncbi.nlm.nih.gov/pubmed/18691455", "http://www.ncbi.nlm.nih.gov/pubmed/19197830", "http://www.ncbi.nlm.nih.gov/pubmed/21556312", "http://www.ncbi.nlm.nih.gov/pubmed/17986515", "http://www.ncbi.nlm.nih.gov/pubmed/15730572", "http://www.ncbi.nlm.nih.gov/pubmed/21755120" ], "ideal_answer": [ "Statin use after subarachnoid hemorrhage has been shown be associated with improved outcomes by some prospective clinical trials. It has been reported that statin use after subarachnoid hemorrhage reduced rates of vasospasm, delayed cerebral ischemia, and mortality. However, other authors have failed to find beneficial effect of statin use in subarachnoid hemorrhage patients." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019161", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013345", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017063", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010043" ], "type": "yesno", "id": "530e131b5937551c09000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Statins have been shown in two recent small phase I/II trials to be associated with a marked reduction in clinical and transcranial Doppler (TCD) evidence of vasospasm after aneurysmal subarachnoid haemorrhage (SAH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19231192", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 658, "text": "Statins did not result in reduced TCD velocities, clinical or angiographic vasospasm, or improvements in global outcome at the time of hospital discharge. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19231192", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 900, "text": "There remains significant uncertainty as to the role of statins in preventing vasospasm after SAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19231192", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 308, "text": "Although the results of 2 randomized clinical trials demonstrated that statin decreases the incidence of symptomatic cerebral vasospasm after aSAH, retrospective studies have failed to confirm this.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19199459", "endSection": "abstract" }, { "offsetInBeginSection": 1473, "offsetInEndSection": 1825, "text": "There were no differences in the incidence of symptomatic vasospasm (25.3 vs 30.5%; p = 0.277), in-hospital mortality rate (18 vs 15%; p = 0.468), length of hospitalization (21 +/- 15 vs 19 +/- 12 days; p = 0.281), or poor outcome at discharge (Glasgow Outcome Scale Scores 1-2: 21.7 vs 18.2%; p = 0.416) between the simvastatin and nonstatin cohorts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19199459", "endSection": "abstract" }, { "offsetInBeginSection": 1882, "offsetInEndSection": 2126, "text": "The uniform introduction of simvastatin did not reduce the incidence of symptomatic cerebral vasospasm, death, or poor outcome in patients with aSAH. Simvastatin was well tolerated, but its benefit may be less than has been previously reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19199459", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 254, "text": "Cholesterol-reducing agents might improve unfavourable outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633351", "endSection": "abstract" }, { "offsetInBeginSection": 2150, "offsetInEndSection": 2326, "text": "We cannot draw any conclusions about the effectiveness and safety of lowering cholesterol in aneurysmal SAH because of insufficient reliable evidence from only one small trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633351", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 119, "text": "Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23392270", "endSection": "abstract" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1466, "text": "There was an improvement in the functional outcome in the simvastatin group at 1, 3 or 6 months in the follow-up; however, this difference was not statistically significant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298376", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1648, "text": " There was benefit of simvastatin in terms of reduction in clinical vasospasm, mortality or improved functional outcome, however, this was not statistically significant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298376", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 713, "text": "Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22929438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: a comparative study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21926584", "endSection": "title" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1845, "text": "In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3-5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21926584", "endSection": "abstract" }, { "offsetInBeginSection": 1859, "offsetInEndSection": 2321, "text": "Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21926584", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 281, "text": "3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved clinical outcomes after ischemic stroke and subarachnoid hemorrhage, but with an increased risk of incidental spontaneous intracerebral hemorrhage (ICH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21755120", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 536, "text": "Statins are known to have pleiotropic vascular effects, some of which may interrupt the pathogenesis of DNDs. Based on promising preliminary reports, many clinicians routinely administer statins to prevent DNDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21125471", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1504, "text": "However, observational studies have not revealed an association between statin-use and reduced DNDs or improved neurological outcomes. Results of RCTs have been inconsistent and limited by small sample size, but together suggest that statins may reduce DNDs, with no clear impact on mortality or neurological recovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21125471", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1797, "text": "the role of statins in the management of patients with SAH remains unclear. Although promising, statins should not, at this time, be considered standard care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21125471", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 660, "text": "In patients with SAH, they may decrease the incidence of symptomatic vasospasm, although the effects on overall outcome are less clear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20934152", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 202, "text": "Statins treatment may have potential clinical impact in vascular disease beyond cholesterol lowering. Its benefits have been documented in cerebral ischaemia and in subarachnoid haemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19912325", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 257, "text": "A recent meta-analysis investigating the efficacy of statin treatment in patients with aneurysmal subarachnoid hemorrhage reported a reduced incidence of vasospasm, delayed cerebral ischemia, and mortality in statin-treated patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19875741", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1711, "text": "The results of the present systematic review do not lend statistically significant support to the finding of a beneficial effect of statins in patients with aneurysmal subarachnoid hemorrhage as reported in a previous meta-analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19875741", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 253, "text": "Pre-treatment with cholesterol lowering drugs of the statin family may exert protective effects in patients with ischaemic stroke and subarachnoid haemorrhage but their effects are not clear in patients with intracerebral haemorrhage (ICH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19614959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Recently, two randomized controlled phase II studies showed that acute initiation of statin treatment directly after aneurysmal subarachnoid hemorrhage (SAH) decreases the incidence of radiologic vasospasm and clinical signs of delayed cerebral ischemia (DCI), and even reduces mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458605", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1367, "text": "We conclude that both the primary and secondary outcome results of this study do not support a beneficial effect of simvastatin in patients with SAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458605", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1215, "text": "Novel uses of their anti-inflammatory properties in sepsis and vasomotor properties in subarachnoid haemorrhage are being further investigated by randomised trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19439205", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 970, "text": "A trend towards a lower mortality within 14 days in patients receiving solely simvastatin and those receiving statin and magnesium as compared with the control group was found. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18691455", "endSection": "abstract" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1546, "text": "Initiation of statin therapy after aneurysmal SAH significantly reduces the incidence of vasospasm, delayed ischemic deficits, and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18658040", "endSection": "abstract" }, { "offsetInBeginSection": 1806, "offsetInEndSection": 1986, "text": "The addition of statins to standard care was not associated with any reduction in the development of vasospasm or improvement in outcomes after aneurysmal subarachnoid hemorrhage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18382320", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 184, "text": "We have previously demonstrated that acute pravastatin therapy after aneurysmal subarachnoid hemorrhage ameliorates vasospasm-related delayed ischemic deficits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17413047", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1617, "text": " This trial demonstrates that acute statin treatment reduces traditional rescue therapy for vasospasm after aneurysmal subarachnoid hemorrhage. Improvement in early outcome has proved robust at 6 months, particularly in relation to physical and psychosocial (Short Form 36) outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17413047", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 214, "text": "The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17029334", "endSection": "abstract" }, { "offsetInBeginSection": 1715, "offsetInEndSection": 1853, "text": "The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17029334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16051891", "endSection": "title" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1861, "text": "The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16051891", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1709, "text": "Acute treatment with pravastatin after aSAH is safe and ameliorates cerebral vasospasm, improves cerebral autoregulation, and reduces vasospasm-related DID.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16049199", "endSection": "abstract" }, { "offsetInBeginSection": 1557, "offsetInEndSection": 1911, "text": " SAH statin users demonstrated significant improvement in 14-day functional outcome, a significantly lower incidence of DCI and cerebral infarctions of any type, as well as prevention of TCD highest mean velocity elevation. However, we did not find a significant statin impact on mortality or global outcome (Modified Rankin Scale) in this small sample. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15730572", "endSection": "abstract" } ] }, { "body": "What is the typical outer diameter of microtubules (tubulin heterodimers)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19565362", "http://www.ncbi.nlm.nih.gov/pubmed/23145817", "http://www.ncbi.nlm.nih.gov/pubmed/9549038", "http://www.ncbi.nlm.nih.gov/pubmed/23729907", "http://www.ncbi.nlm.nih.gov/pubmed/7161484", "http://www.ncbi.nlm.nih.gov/pubmed/18085218" ], "ideal_answer": [ "Microtubules are highly anisotropic structures built from tubulin heterodimers. They are hollow cylindrical shells with a \u223c 25 nm (24nm - 25nm) outer diameter." ], "exact_answer": [ "24nm - 25 nm" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045298", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005874" ], "type": "factoid", "id": "553f72edab98a37113000007", "snippets": [ { "offsetInBeginSection": 418, "offsetInEndSection": 562, "text": "microtubules are highly anisotropic structures built from tubulin heterodimers. They are hollow cylindrical shells with a \u223c 25\u00a0nm outer diameter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729907", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 431, "text": "single microtubules (diameter 25 nm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23145817", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 664, "text": "The individual microtubules measured about 24 nm in outer diameter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7161484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Microtubules are hollow tubes some 25 nm in diameter participating in the eukaryotic cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19565362", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 583, "text": "Microtubule assembly is accompanied by hydrolysis of GTP associated with beta-tubulin so that microtubules consist principally of \"GDP-tubulin\" stabilized by a short \"GTP cap.\" Microtubules are polar, cylindrical structures some 25 nm in diameter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18085218", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 591, "text": "They are hollow cylindrical shells with a \u223c 25\u00a0nm outer diameter and are tens of microns long", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729907", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 582, "text": "Microtubule assembly is accompanied by hydrolysis of GTP associated with beta-tubulin so that microtubules consist principally of \"GDP-tubulin\" stabilized by a short \"GTP cap.\" Microtubules are polar, cylindrical structures some 25 nm in diameter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18085218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Microtubules are hollow tubes some 25 nm in diameter participating in the eukaryotic cytoskeleton", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19565362", "endSection": "abstract" } ] }, { "body": "Does molindone affect body weight?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10796464", "http://www.ncbi.nlm.nih.gov/pubmed/10548138", "http://www.ncbi.nlm.nih.gov/pubmed/2671060", "http://www.ncbi.nlm.nih.gov/pubmed/3780420", "http://www.ncbi.nlm.nih.gov/pubmed/8800628", "http://www.ncbi.nlm.nih.gov/pubmed/20502331", "http://www.ncbi.nlm.nih.gov/pubmed/8290673", "http://www.ncbi.nlm.nih.gov/pubmed/7481576", "http://www.ncbi.nlm.nih.gov/pubmed/18794207", "http://www.ncbi.nlm.nih.gov/pubmed/11488257", "http://www.ncbi.nlm.nih.gov/pubmed/12518268", "http://www.ncbi.nlm.nih.gov/pubmed/17253473", "http://www.ncbi.nlm.nih.gov/pubmed/20494268", "http://www.ncbi.nlm.nih.gov/pubmed/842709", "http://www.ncbi.nlm.nih.gov/pubmed/22372512", "http://www.ncbi.nlm.nih.gov/pubmed/10553730" ], "ideal_answer": [ "Yes, molindone has a tendency to cause weight loss or limited weight gain." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015431", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015430", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008972", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001836", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001837", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001835", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019440", "http://www.biosemantics.org/jochem#4249624" ], "type": "yesno", "id": "52cae04c03868f1b06000024", "snippets": [ { "offsetInBeginSection": 1464, "offsetInEndSection": 1540, "text": "Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22372512", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 712, "text": "A large-scale trial comparing a first-generation antipsychotic (molindone) with newer agents did not find significant differences in treatment response, although the newer antipsychotics were associated with more severe weight gain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20502331", "endSection": "abstract" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1602, "text": "No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20494268", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1349, "text": "The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20494268", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1698, "text": "Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18794207", "endSection": "abstract" }, { "offsetInBeginSection": 2130, "offsetInEndSection": 2320, "text": "Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17253473", "endSection": "abstract" }, { "offsetInBeginSection": 2490, "offsetInEndSection": 2670, "text": "Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17253473", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 459, "text": "Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12518268", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1037, "text": "Loxapine and molindone induce weight decreases, and these exceptions are difficult to explain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11488257", "endSection": "abstract" }, { "offsetInBeginSection": 2837, "offsetInEndSection": 2983, "text": "It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10796464", "endSection": "abstract" }, { "offsetInBeginSection": 3154, "offsetInEndSection": 3339, "text": "Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10796464", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 844, "text": "Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10553730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10548138", "endSection": "abstract" }, { "offsetInBeginSection": 2144, "offsetInEndSection": 2260, "text": "Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8800628", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 385, "text": "Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7481576", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 840, "text": "On average, molindone patients lost 5 pounds over the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8290673", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 856, "text": "Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2671060", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 407, "text": " Monthly weights and neuroleptic dosages during the first three months of psychiatric hospitalization were compared between matched groups of patients receiving molindone, a combination of molindone and other neuroleptics, or other neuroleptic drugs. We found no significant differences in weight gain among the three groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3780420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/842709", "endSection": "abstract" } ] }, { "body": "What is the genetic basis of propionic acidemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18790721", "http://www.ncbi.nlm.nih.gov/pubmed/10447268", "http://www.ncbi.nlm.nih.gov/pubmed/19157943", "http://www.ncbi.nlm.nih.gov/pubmed/15235904", "http://www.ncbi.nlm.nih.gov/pubmed/11592820", "http://www.ncbi.nlm.nih.gov/pubmed/12409268", "http://www.ncbi.nlm.nih.gov/pubmed/17051315", "http://www.ncbi.nlm.nih.gov/pubmed/12007220", "http://www.ncbi.nlm.nih.gov/pubmed/12559849", "http://www.ncbi.nlm.nih.gov/pubmed/9683601", "http://www.ncbi.nlm.nih.gov/pubmed/15164333", "http://www.ncbi.nlm.nih.gov/pubmed/21094621", "http://www.ncbi.nlm.nih.gov/pubmed/23053474", "http://www.ncbi.nlm.nih.gov/pubmed/9385377", "http://www.ncbi.nlm.nih.gov/pubmed/8188292", "http://www.ncbi.nlm.nih.gov/pubmed/8023851", "http://www.ncbi.nlm.nih.gov/pubmed/11245989", "http://www.ncbi.nlm.nih.gov/pubmed/15464417", "http://www.ncbi.nlm.nih.gov/pubmed/15059621", "http://www.ncbi.nlm.nih.gov/pubmed/15949719", "http://www.ncbi.nlm.nih.gov/pubmed/21986446", "http://www.ncbi.nlm.nih.gov/pubmed/2154743", "http://www.ncbi.nlm.nih.gov/pubmed/22033733", "http://www.ncbi.nlm.nih.gov/pubmed/12385775", "http://www.ncbi.nlm.nih.gov/pubmed/10502773", "http://www.ncbi.nlm.nih.gov/pubmed/19099776", "http://www.ncbi.nlm.nih.gov/pubmed/11749052", "http://www.ncbi.nlm.nih.gov/pubmed/12757933", "http://www.ncbi.nlm.nih.gov/pubmed/20549364", "http://www.ncbi.nlm.nih.gov/pubmed/11136555", "http://www.ncbi.nlm.nih.gov/pubmed/2095843", "http://www.ncbi.nlm.nih.gov/pubmed/10329019", "http://www.ncbi.nlm.nih.gov/pubmed/11914040", "http://www.ncbi.nlm.nih.gov/pubmed/2249848", "http://www.ncbi.nlm.nih.gov/pubmed/10820128", "http://www.ncbi.nlm.nih.gov/pubmed/20950151", "http://www.ncbi.nlm.nih.gov/pubmed/19025475", "http://www.ncbi.nlm.nih.gov/pubmed/10101253", "http://www.ncbi.nlm.nih.gov/pubmed/9887338" ], "ideal_answer": [ "Mutations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA carboxylase." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056693" ], "type": "summary", "id": "5318813ab166e2b806000016", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 128, "text": "utations in the PCCA or PCCB genes coding for alpha and beta subunits of propionyl CoA carboxylase can cause propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15949719", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 228, "text": "propionic acidemia (PA) can result from mutations in either of the genes PCCA or PCCB, which encode the alpha and beta subunits, respectively, of the mitochondrial enzyme propionyl CoA-carboxylase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10101253", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 129, "text": "eficiency of propionyl-CoA carboxylase (PCC; alpha 4 beta 4) results in the rare, autosomal recessive disease propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8023851", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 290, "text": "PA is caused by mutations in either the PCCA or PCCB genes encoding the \u03b1- and \u03b2-subunits of the PCC enzyme ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053474", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 122, "text": "eficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033733", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 466, "text": "Recent studies have identified the genomic mutations in the genes PCCA and PCCB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21986446", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 77, "text": "ropionic acidemia is an organic acidemia that can lead to metabolic acidosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21986446", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 184, "text": "plicing defects account for 16% of the mutant alleles in the PCCA and PCCB genes, encoding both subunits of the propionyl-CoA carboxylase (PCC) enzyme, defective in propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21094621", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 137, "text": "ropionic acidemia (PA) is an autosomal recessive disorder of metabolism caused by a deficiency of propionyl-coenzyme A carboxylase (PCC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20950151", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 296, "text": "In the PA patients, we have identified four different changes in the PCCA gene, including one novel one (c.414+5G>A) affecting the splicing process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20549364", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 86, "text": "utations in either the PCCA or PCCB genes are responsible for propionic acidemia (PA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19157943", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 360, "text": "Propionic acidemia is a common organic acidemia, caused by deficiency of propionyl-CoA carboxylase (PCC), which catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA. PCC is a dodecameric enzyme of alpha-PCC and beta-PCC subunits, nuclearly encoded by genes PCCA and PCCB, respectively. Mutation in either gene cause propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19099776", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 272, "text": "PA is inherited in an autosomal recessive fashion involving mutations in PCCA or PCCB encoding the alpha and beta subunits of propionyl-CoA carboxylase (PCC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19025475", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 656, "text": "Two siblings affected with propionic acidemia were screened for putative mutations in PCCA and PCCB genes coding alpha and beta subunits of propionyl-coenzyme A (CoA) carboxylase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18790721", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 158, "text": "ropionic acidemia results from mutations in either of the two genes, PCCA or PCCB, that encode the two subunits of the propionyl-CoA carboxylase (PCC) enzyme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17051315", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 118, "text": "utations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA carboxylase, result in propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15464417", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 273, "text": " we analyze splicing mutations identified in propionic acidemia patients to clarify their functional effects and their involvement in the disease phenotype. Two mutations in the PCCA gene detected in homozygous patients and involving consensus splice sequences ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15235904", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 324, "text": "An enzyme deficiency can result from mutations in either PCCA or PCCB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15059621", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 122, "text": "(PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15059621", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 391, "text": "Mutations in either gene cause PA and to date, up to 47 different allelic variations in the PCCB gene have been identified in different population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757933", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 184, "text": "ropionic acidemia (PA) is a recessive disorder caused by a deficiency of propionyl-CoA carboxylase (PCC), a dodecameric enzyme composed of two different proteins alpha-PCC and beta-PC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757933", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 412, "text": "PCC is a multimeric protein composed of two different alpha- and beta-PCC subunits, nuclearly encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause the clinically heterogeneous disease propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12559849", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 641, "text": "More than 24 mutations have been found in the PCCA gene in patients with PA, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12385775", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 272, "text": "ropionic acidemia (PA, MIM 232000 and 232050) is caused by a deficiency of mitochondrial biotin-dependent propionyl-CoA carboxylase (PCC, EC 6.4.1.3), a heteropolymeric enzyme composed of alpha and beta subunits, which are encoded by the PCCA and PCCB genes, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12385775", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 560, "text": "Approximately 60 mutations have been reported in the nuclear genes PCCA and PCCB that encode the two PCC subunits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12007220", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 75, "text": "eficiency of propionyl-CoA carboxylase (PCC) results in propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12007220", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 107, "text": "ropionic acidemia can result from mutations in the PCCA or PCCB genes encoding the alpha and beta subunits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11914040", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 170, "text": "ropionic acidemia is an inherited metabolic disorder caused by deficiency of propionyl-CoA carboxylase, a dodecameric enzyme composed of alpha-PCC and beta-PCC subunits ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11749052", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 677, "text": "A genetic deficiency of PCC activity causes propionic acidemia, a potentially fatal disease with onset in severe cases in the newborn period. Affected patients may have mutations of either the PCCA or PCCB gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11592820", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 358, "text": "PCC is composed of two equal subunits, alpha and beta, which are encoded by two separate genes at two distinct human loci. Mutations of either gene in humans results in propionic acidemia (PA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11245989", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 349, "text": "Deficiency of PCC results in propionic acidemia (PA), a metabolic disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11136555", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 353, "text": " PCC consists of two subunits, alpha and beta, encoded by the PCCA and PCCB genes, respectively. Inherited PCC deficiency due to mutations in either gene results in propionic acidemia (PA),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10820128", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 75, "text": "mutations in the PCCA and PCCB genes causing propionic acidemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502773", "endSection": "title" }, { "offsetInBeginSection": 98, "offsetInEndSection": 226, "text": "Mutations in the PCCA and PCCB genes, which encode the a and b subunits of this heteropolymer, result in propionic acidemia (PA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10447268", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 254, "text": "ropionic acidemia is a rare autosomal recessive disorder of intermediary metabolism. It is caused by a deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC, EC 6.4.1.3), a heteropolymeric protein composed of two subunits, alpha and beta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10329019", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 222, "text": "ropionic acidemia is an autosomal recessive disorder caused by a deficiency in the mitochondrial enzyme propionyl-CoA carboxylase (PCC). PCC is composed of two subunits, alpha and beta, encoded by the PCCA and PCCB genes,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9887338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1534, "text": "Propionyl-CoA carboxylase (PCC) is a mitochondrial biotin-dependent enzyme composed of an equal number of alpha and beta subunits. Mutations in the PCCA (alpha subunit) or PCCB (beta subunit) gene can cause the inherited metabolic disease propionic acidemia (PA), which can be life threatening in the neonatal period. Lack of data on the genomic structure of PCCB has been a significant impediment to full characterization of PCCB mutant chromosomes. In this study, we describe the genomic organization of the coding sequence of the human PCCB gene and the characterization of mutations causing PA in a total of 29 unrelated patients-21 from Spain and 8 from Latin America. The implementation of long-distance PCR has allowed us to amplify the regions encompassing the exon/intron boundaries and all the exons. The gene consists of 15 exons of 57-183 bp in size. All splice sites are consistent with the gt/ag rule. The availability of the intron sequences flanking each exon has provided the basis for implementation of screening for mutations in the PCCB gene. A total of 56/58 mutant chromosomes studied have been defined, with a total of 16 different mutations detected. The mutation spectrum includes one insertion/deletion, two insertions, 10 missense mutations, one nonsense mutation, and two splicing defects. Thirteen of these mutations correspond to those not described yet in other populations. The mutation profile found in the chromosomes from the Latin American patients basically resembles that of the Spanish patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9683601", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 401, "text": "Inherited deficiency of PCC due to mutations in either the PCCA or the PCCB gene results in propionic acidemia (PA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9385377", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 342, "text": "Mutations of the PCCA (alpha subunit) or PCCB (beta subunit) gene cause the inherited metabolic disease, propionic acidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8188292", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 244, "text": "We have detected three types of mutation in the same exon of the coding sequence of beta-subunit of PCC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2095843", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 114, "text": "ropionic acidemia is an inborn error of organic acid metabolism caused by deficiency of propionyl-CoA carboxylase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2095843", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 395, "text": "we have identified two mutations of the PCCB gene in a propionic acidemia patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2249848", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 321, "text": "ropionic acidemia is an inherited disorder of organic acid metabolism that is caused by deficiency of propionyl-CoA carboxylase (PCC; EC 6.4.1.3). Affected patients fall into two complementation groups, pccA and pccBC (subgroups B, C, and BC), resulting from deficiency of the nonidentical alpha and beta subunits of PCC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2154743", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 62, "text": "ropionic acidemia (PA) is an autosomal recessive inborn error", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12409268", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 345, "text": "It is caused by a deficiency of propionyl-CoA carboxylase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12409268", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 534, "text": "PCC is a heteropolymeric enzyme composed of alpha- and beta-subunits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12409268", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 890, "text": "Mutation analysis confirmed the diagnosis of propionic acidemia (PA) with compound heterozygosity for 2 new missense mutations L417W/Q293E in the PCCA gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15164333", "endSection": "abstract" } ] }, { "body": "Which protein phosphatase has been found to interact with the heat shock protein, HSP20?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24244723", "http://www.ncbi.nlm.nih.gov/pubmed/21493896" ], "ideal_answer": [ "Protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, revealed an association between Hsp20 and PP1. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.", "Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling." ], "exact_answer": [ "Protein phosphatase 1", "PP1" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016791", "http://www.uniprot.org/uniprot/HSP20_NIPBR" ], "type": "factoid", "id": "5506ce078e1671127b00000b", "snippets": [ { "offsetInBeginSection": 1120, "offsetInEndSection": 1453, "text": " Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Indeed, human genetic variants of inhibitor-1 (G147D) or Hsp20 (P20L) result in reduced binding and inhibition of protein phosphatase-1, suggesting aberrant enzymatic regulation in human carriers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21493896", "endSection": "title" }, { "offsetInBeginSection": 510, "offsetInEndSection": 1420, "text": " Hsp20 overexpression in intact animals resulted in significant enhancement of cardiac function, coupled with augmented Ca cycling and sarcoplasmic reticulum Ca load in isolated cardiomyocytes. This was associated with specific increases in phosphorylation of phospholamban (PLN) at both Ser16 and Thr17, relieving its inhibition of the apparent Ca affinity of SERCA2a. Accordingly, the inotropic effects of Hsp20 were abrogated in cardiomyocytes expressing nonphosphorylatable PLN (S16A/T17A). Interestingly, the activity of type 1 protein phosphatase (PP1), a known regulator of PLN signaling, was significantly reduced by Hsp20 overexpression, suggesting that the Hsp20 stimulatory effects are partially mediated through the PP1-PLN axis. This hypothesis was supported by cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, which revealed an association between Hsp20, PP1, and PLN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21493896", "endSection": "abstract" }, { "offsetInBeginSection": 1564, "offsetInEndSection": 1799, "text": "Hsp20 is a novel regulator of sarcoplasmic reticulum Ca cycling by targeting the PP1-PLN axis. These findings, coupled with the well-recognized cardioprotective role of Hsp20, suggest a dual benefit of targeting Hsp20 in heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21493896", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1255, "text": "Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244723", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1254, "text": "Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244723", "endSection": "abstract" } ] }, { "body": "What is the risk in G-CSF treatment for severe congenital neutropenia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15642668", "http://www.ncbi.nlm.nih.gov/pubmed/20456363", "http://www.ncbi.nlm.nih.gov/pubmed/20237318", "http://www.ncbi.nlm.nih.gov/pubmed/22371884", "http://www.ncbi.nlm.nih.gov/pubmed/21052952", "http://www.ncbi.nlm.nih.gov/pubmed/12555210" ], "ideal_answer": [ "Severe congenital neutropenia is a rare hematological condition causing severe chronic neutropenia. Treatment with the myeloid growth factor, granulocyte-colony stimulating factor (G-CSF) is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of the patients evolve to develop acute myeloid leukemia or myelodysplastic syndromes, necessitating careful clinical monitoring." ], "concepts": [ "http://www.biosemantics.org/jochem#4250245", "http://www.disease-ontology.org/api/metadata/DOID:0050590", "http://www.uniprot.org/uniprot/CSF3_CANFA" ], "type": "summary", "id": "55031406e9bde69634000021", "snippets": [ { "offsetInBeginSection": 211, "offsetInEndSection": 1301, "text": "We obtained serial hematopoietic samples from an SCN patient who developed AML 17 years after the initiation of G-CSF treatment. Next- generation sequencing was performed to identify mutations during disease progression. In the AML phase, we found 12 acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co-occurred in a subpopulation of progenitor cells already in the early SCN phase. This population expanded over time, whereas clones harboring only CSF3R mutations disappeared from the BM. The other 9 mutations were only apparent in the AML cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred autonomous proliferation to myeloid progenitors was found. We conclude that progression from SCN to AML is a multistep process, with distinct mutations arising early during the SCN phase and others later in AML development. The sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a driver of leukemic transformation in this case of SCN", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371884", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 441, "text": "This chapter focuses on cyclic and congenital neutropenia, two very interesting and rare hematological conditions causing severe chronic neutropenia. Both disorders respond well to treatment with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21052952", "endSection": "abstract" }, { "offsetInBeginSection": 1688, "offsetInEndSection": 1957, "text": "Treatment with G-CSF is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of severe congenital neutropenia patients evolve to develop acute myeloid leukemia, necessitating careful clinical monitoring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21052952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "In severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20456363", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 332, "text": "Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced the frequency and severity of infections, but its possible influence on the risk of malignancy is not known", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15642668", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1238, "text": "No septic deaths occurred during G-CSF therapy. Thirteen cases of MDS/AL were recorded. The cumulative incidence of MDS/AL was 2.7% (SD 1.3%) at 10 years and 8.1% (SD 2.7%) at 20 years", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15642668", "endSection": "abstract" }, { "offsetInBeginSection": 1488, "offsetInEndSection": 1706, "text": "Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15642668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20456363", "endSection": "title" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1139, "text": "This specifically applies to children with severe congenital neutropenia who receive lifelong treatment with G-CSF and in which the high susceptibility to develop MDS and acute myeloid leukemia (AML) has now become a major clinical concern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20237318", "endSection": "abstract" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1622, "text": "Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15642668", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1205, "text": "As of January 1, 2000, myelodysplasia (MDS) or acute myelogenous leukemia (AML) has occurred in 35 of 387 patients with congenital neutropenia with a cumulative risk of 13% after 8 years of G-CSF treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12555210", "endSection": "abstract" } ] }, { "body": "Neurostimulation of which nucleus is used for treatment of dystonia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17093249", "http://www.ncbi.nlm.nih.gov/pubmed/11254790", "http://www.ncbi.nlm.nih.gov/pubmed/11481711", "http://www.ncbi.nlm.nih.gov/pubmed/21549607", "http://www.ncbi.nlm.nih.gov/pubmed/12151848", "http://www.ncbi.nlm.nih.gov/pubmed/24268100", "http://www.ncbi.nlm.nih.gov/pubmed/16410002", "http://www.ncbi.nlm.nih.gov/pubmed/19576854", "http://www.ncbi.nlm.nih.gov/pubmed/15689584", "http://www.ncbi.nlm.nih.gov/pubmed/17277672", "http://www.ncbi.nlm.nih.gov/pubmed/16717218", "http://www.ncbi.nlm.nih.gov/pubmed/24292857", "http://www.ncbi.nlm.nih.gov/pubmed/25127231", "http://www.ncbi.nlm.nih.gov/pubmed/17973330", "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "http://www.ncbi.nlm.nih.gov/pubmed/20482602", "http://www.ncbi.nlm.nih.gov/pubmed/23037556" ], "ideal_answer": [ "Neurostimulation of globus pallidus internus is effective for treatment of dystonia. Ventral intermediate thalamic nucleus has also been tested for neurostimulation in dystonia patients." ], "exact_answer": [ "globus pallidus internus" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:543" ], "type": "factoid", "id": "54fc99f36ad7dcbc12000004", "snippets": [ { "offsetInBeginSection": 829, "offsetInEndSection": 1044, "text": "Bilateral globus pallidus internus (GPi) DBS was performed in five SD patients and unilateral ventralis oralis anterior and posterior (Voa/Vop) nucleus of the thalamus DBS in two post-stroke hemiballismus patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: Deep brain stimulation of the internal pallidum (GPi-DBS) is effective for various types of drug-refractory primary dystonias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268100", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 696, "text": "METHODS: In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "endSection": "abstract" }, { "offsetInBeginSection": 1996, "offsetInEndSection": 2379, "text": "INTERPRETATION: 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 618, "text": "We describe a patient who received bilateral globus pallidus internus DBS for dystonia with initially good clinical response, but the device eventually failed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576854", "endSection": "title" }, { "offsetInBeginSection": 163, "offsetInEndSection": 439, "text": "Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576854", "endSection": "abstract" }, { "offsetInBeginSection": 1789, "offsetInEndSection": 1927, "text": "INTERPRETATION: Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Pallidal deep-brain stimulation in primary generalized or segmental dystonia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17093249", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17093249", "endSection": "abstract" }, { "offsetInBeginSection": 1867, "offsetInEndSection": 2029, "text": "CONCLUSIONS: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17093249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "OBJECTIVE: To assess the effects of bilateral pallidal deep brain stimulation (DBS) on mood and cognitive performance in patients with dystonia before surgery (at baseline, while patients received their usual treatment) and 12 months postoperatively (while patients received neurostimulation and their medications) in a multicenter prospective study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16717218", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1433, "text": "CONCLUSIONS: Bilateral pallidal stimulation has a good benefit-to-risk ratio as it did not negatively affect cognitive performance and mood in primary dystonia, while a significant motor improvement was obtained.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16717218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 513, "text": "Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16410002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15689584", "endSection": "title" }, { "offsetInBeginSection": 252, "offsetInEndSection": 437, "text": "METHODS: We performed a prospective, controlled, multicenter study assessing the efficacy and safety of bilateral pallidal stimulation in 22 patients with primary generalized dystonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15689584", "endSection": "abstract" }, { "offsetInBeginSection": 1729, "offsetInEndSection": 1912, "text": "CONCLUSIONS: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15689584", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1312, "text": "Bilateral pallidotomy or pallidal stimulation may provide major benefit especially in patients with generalized, disabling dystonia with the most dramatic improvements in dystonia type 1 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12151848", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 498, "text": "This suggests that neurostimulation of the VIM may be an effective treatment for myoclonus in pharmacologically intractable IMDS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11481711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "We report on the effects of bilateral neurostimulation of the ventral intermediate thalamic nucleus (VIM) in a patient with medically intractable and progressing inherited myoclonus dystonia syndrome (IMDS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11481711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11481711", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Pallidal and thalamic neurostimulation in severe tardive dystonia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11254790", "endSection": "title" }, { "offsetInBeginSection": 101, "offsetInEndSection": 281, "text": "After informed consent, a bilateral stereotactic electrode placement targeting the ventral intermediate thalamic nucleus (VIM) and the globus pallidus internus (GPi) was performed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11254790", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 584, "text": "Stimulation of the VIM did not improve the hyperkinetic movements and simultaneous stimulation of both the GPi and the VIM did not result in any additional benefit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11254790", "endSection": "abstract" }, { "offsetInBeginSection": 1733, "offsetInEndSection": 1854, "text": "Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576854", "endSection": "abstract" }, { "offsetInBeginSection": 1947, "offsetInEndSection": 2119, "text": "3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "endSection": "abstract" }, { "offsetInBeginSection": 2118, "offsetInEndSection": 2313, "text": " This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "endSection": "abstract" }, { "offsetInBeginSection": 1996, "offsetInEndSection": 2184, "text": "INTERPRETATION: 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "endSection": "abstract" }, { "offsetInBeginSection": 2185, "offsetInEndSection": 2379, "text": "This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "endSection": "abstract" }, { "offsetInBeginSection": 1761, "offsetInEndSection": 1881, "text": "Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576854", "endSection": "abstract" }, { "offsetInBeginSection": 1968, "offsetInEndSection": 2139, "text": "3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "endSection": "abstract" } ] }, { "body": "Which myosin isozymes are located within the pericuticular necklace of the hair cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12471897", "http://www.ncbi.nlm.nih.gov/pubmed/17048225", "http://www.ncbi.nlm.nih.gov/pubmed/12486594", "http://www.ncbi.nlm.nih.gov/pubmed/9182663" ], "ideal_answer": [ "The hair cell is located in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes. Within the pericuticular necklace, a domain of the hair cell, certain unconventional myosin isozymes are located, namely myosins-Ibeta, myosin-VI, and myosin-VIIa." ], "exact_answer": [ [ "myosins-Ibeta" ], [ "myosin-VI" ], [ "myosin-VIIa" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035315", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002093", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032507" ], "type": "list", "id": "5548da00f35db7552600000b", "snippets": [ { "offsetInBeginSection": 416, "offsetInEndSection": 527, "text": "Myosin 1 beta, VI, VIIa and probably XV are all expressed within a single cell in the inner ear, the hair cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12471897", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 692, "text": "The myosin isozymes expressed in the hair cell all have unique domains of expression and in some areas, such as the pericuticular necklace, several domains overlap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12471897", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1163, "text": "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182663", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 281, "text": "four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182663", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 687, "text": "The myosin isozymes expressed in the hair cell all have unique domains of expression and in some areas, such as the pericuticular necklace, several domains overlap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12471897", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1292, "text": "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined the distribution of four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182663", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 533, "text": "This study examined the changes of myosin VI and myosin VIIa, two unconventional myosins that are critical for normal hair cell formation and function, during hair cell death and regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17048225", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1298, "text": "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182663", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1297, "text": "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182663", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 691, "text": "The myosin isozymes expressed in the hair cell all have unique domains of expression and in some areas, such as the pericuticular necklace, several domains overlap", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12471897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined the distribution of four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182663", "endSection": "abstract" } ] }, { "body": "Which is the treatment strategy followed in spinocerebellar ataxia type 3 for CAG removal?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23659897" ], "ideal_answer": [ "The novel treatment strategy proposed for treatment of Spinocerebellar ataxia type 3 is the removal of the toxic polyglutamine repeat from the ataxin-3 protein through antisense oligonucleotide-mediated exon skipping while maintaining important wild type functions of the protein." ], "type": "summary", "id": "571394701174fb175500000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Spinocerebellar ataxia type 3 is caused by a polyglutamine expansion in the ataxin-3 protein, resulting in gain of toxic function of the mutant protein. The expanded glutamine stretch in the protein is the result of a CAG triplet repeat expansion in the penultimate exon of the ATXN3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 831, "text": "we propose a novel protein modification approach to reduce mutant ataxin-3 toxicity by removing the toxic polyglutamine repeat from the ataxin-3 protein through antisense oligonucleotide-mediated exon skipping while maintaining important wild type functions of the protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1184, "text": "exon skipping may be a novel therapeutic approach to reduce polyglutamine-induced toxicity in spinocerebellar ataxia type 3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "endSection": "title" } ] }, { "body": "Where is the angiogenin binding element located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24122807", "http://www.ncbi.nlm.nih.gov/pubmed/7875314", "http://www.ncbi.nlm.nih.gov/pubmed/12515546", "http://www.ncbi.nlm.nih.gov/pubmed/9413551", "http://www.ncbi.nlm.nih.gov/pubmed/2813401", "http://www.ncbi.nlm.nih.gov/pubmed/3289612" ], "ideal_answer": [ "Angiogenin binds to CT repeats that are abundant in the nontranscribed region of the ribosomal RNA gene. An angiogenin-binding DNA sequence (CTCTCTCTCTCTCTCTCCCTC) has been identified and designated angiogenin-binding element (ABE)." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004602", "http://www.uniprot.org/uniprot/ANGI_GORGO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032311" ], "type": "summary", "id": "551d8b3a6b348bb82c000011", "snippets": [ { "offsetInBeginSection": 362, "offsetInEndSection": 542, "text": "ANG binds at the upstream control element (UCE) of the promoter and enhances promoter occupancy of RNA Pol I as well as the selectivity factor SL1 components TAFI 48 and TAFI 110. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24122807", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 852, "text": " Here we report that angiogenin binds to CT repeats that are abundant in the nontranscribed region of the ribosomal RNA gene. An angiogenin-binding DNA sequence (CTCTCTCTCTCTCTCTCCCTC) has been identified and designated angiogenin-binding element (ABE). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12515546", "endSection": "abstract" } ] }, { "body": "Which proteins cause cytoplasmic sequestration of NF-kB?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22975329", "http://www.ncbi.nlm.nih.gov/pubmed/12972430", "http://www.ncbi.nlm.nih.gov/pubmed/12399470", "http://www.ncbi.nlm.nih.gov/pubmed/16136188", "http://www.ncbi.nlm.nih.gov/pubmed/20845110", "http://www.ncbi.nlm.nih.gov/pubmed/8692272", "http://www.ncbi.nlm.nih.gov/pubmed/10454561", "http://www.ncbi.nlm.nih.gov/pubmed/8804077", "http://www.ncbi.nlm.nih.gov/pubmed/9566872", "http://www.ncbi.nlm.nih.gov/pubmed/7809091" ], "ideal_answer": [ "In unstimulated cells, NF-kB transcription factors are retained in the cytoplasm with the inhibitory activity of I-kBs, Sef, NF-kB1 (p105) and NF-kB2 (p100)." ], "exact_answer": [ [ "I-kBs" ], [ "Sef" ], [ "NF-kB1 (p105)" ], [ "NF-kB2 (p100)" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008588", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035525", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032088", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042994", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007253", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051220", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016328", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071159", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042347" ], "type": "list", "id": "530db83b38c1322806000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Sef is an inhibitor of proinflammatory cytokine signaling, acting by cytoplasmic sequestration of NF-\u03baB", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975329", "endSection": "title" }, { "offsetInBeginSection": 70, "offsetInEndSection": 268, "text": "According to the classical model, NF-\u03baB is retained in the cytoplasm of resting cells via binding to inhibitory, I\u03baB proteins and translocates into the nucleus upon their ligand-induced degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975329", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 649, "text": "Like I\u03baBs, Sef sequesters NF-\u03baB in the cytoplasm of resting cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975329", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 233, "text": "The activity of NF-\u03baB is tightly controlled through its cytoplasmic sequestration by specific inhibitors, I\u03baBs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20845110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The inhibitor of NF-kappaB (IkappaB) family of proteins is believed to regulate NF-kappaB activity by cytoplasmic sequestration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16136188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "IkappaBalpha is an inhibitory molecule that sequesters NF-kappaB dimers in the cytoplasm of unstimulated cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12972430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "p105.Ikappa Bgamma and prototypical Ikappa Bs use a similar mechanism to bind but a different mechanism to regulate the subcellular localization of NF-kappa B", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12399470", "endSection": "title" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1501, "text": "We show that the death domain of p105 (also of IkappaBgamma) is essential for the cytoplasmic sequestration of NF-kappaB by p105 and IkappaBgamma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12399470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "In unstimulated cells, NF-kappaB transcription factors are retained in the cytoplasm by inhibitory IkappaB proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10454561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "The ability of the IkappaB alpha protein to sequester dimeric NF-kappaB/Rel proteins in the cytoplasm provides an effective mechanism for regulating the potent transcriptional activation properties of NF-kappaB/Rel family members.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9566872", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1201, "text": "The presence of a discrete nuclear import sequence in IkappaB alpha suggests that cytoplasmic sequestration of the NF-kappaB/Rel-IkappaB alpha complex is a consequence of the mutual masking of the NLS within NF-kappaB/Rel proteins and the import sequence within IkappaB alpha.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9566872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "The viral Tax protein, which is encoded by human T-cell leukaemia virus HTLV-I, activates nuclear translocation of the NF-kappa B/Rel transcription factors and relieves cytoplasmic sequestration of RelA and Rel by heterodimerization with NF-kappa B1/p1O5 (refs 1,2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8692272", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 711, "text": "The I-kappa B protein, which is necessary for the cytoplasmic sequestration of the NF-kappa B transcription factor complex, was identified specifically in regions of limbic, hypothalamic, and autonomic nuclei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8804077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Human T-cell leukemia virus type I Tax-protein-mediated activation of NF-kappa B from p100 (NF-kappa B2)-inhibited cytoplasmic reservoirs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7809091", "endSection": "title" }, { "offsetInBeginSection": 407, "offsetInEndSection": 668, "text": "The preexisting NF-kappa B proteins are retained in the cytoplasm of cells by association with inhibitory ankyrin-motif-containing I kappa B proteins, primarily I kappa B-alpha but also including the precursor proteins p105 (NF-kappa B1) and p100 (NF-kappa B2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7809091", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of Marchesani syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10707143", "http://www.ncbi.nlm.nih.gov/pubmed/8914744", "http://www.ncbi.nlm.nih.gov/pubmed/20301293", "http://www.ncbi.nlm.nih.gov/pubmed/19396027", "http://www.ncbi.nlm.nih.gov/pubmed/6739588", "http://www.ncbi.nlm.nih.gov/pubmed/19836009", "http://www.ncbi.nlm.nih.gov/pubmed/12525539", "http://www.ncbi.nlm.nih.gov/pubmed/14598350", "http://www.ncbi.nlm.nih.gov/pubmed/11941487" ], "ideal_answer": [ "Marchesani syndrome is transmitted either by an autosomal dominant (mutations in FBN1) or an autosomal recessive (mutations in ADAMTS10) mode of inheritance" ], "exact_answer": [ "autosomal dominant or autosomal recessive" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056846", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582" ], "type": "factoid", "id": "532f0bd6d6d3ac6a3400002d", "snippets": [ { "offsetInBeginSection": 534, "offsetInEndSection": 633, "text": "Autosomal recessive and autosomal dominant WMS cannot be distinguished by clinical findings alone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Weill-Marchesani syndrome (WMS) is a well-characterized disorder in which patients develop eye and skeletal abnormalities. Autosomal-recessive and autosomal-dominant forms of WMS are caused by mutations in ADAMTS10 and FBN1 genes, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19836009", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 830, "text": "Finally, WMS is transmitted either by an autosomal dominant or an autosomal recessive (AR) mode of inheritance, GD by an autosomal recessive mode of inheritance and AD by an autosomal dominant mode of inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19396027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Weill-Marchesani syndrome (WMS) is a rare condition characterized by short stature, brachydactyly, joint stiffness, and characteristic eye abnormalities including microspherophakia, ectopia of lens, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described for WMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14598350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by short stature, brachydactyly, joint stiffness, and characteristic eye anomalies including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described and a gene for AR WMS has recently been mapped to chromosome 19p13.3-p13.2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525539", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 325, "text": "Both autosomal recessive and autosomal dominant modes of inheritance have been described in association with WMS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11941487", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 440, "text": "We report 6 patients with Weill-Marchesani syndrome (with or without ocular involvement) in three generations, identified by screening 26 members of two families. This is the largest family in the literature showing an autosomal dominant pattern of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10707143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Weill-Marchesani syndrome comprises short stature, brachydactyly, microspherophakia, glaucoma, and ectopia lentis is regarded as an autosomal recessive trait", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8914744", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 323, "text": "We present two families each with affected individuals in 3 generations demonstrating autosomal dominant inheritance of Weill-Marchesani syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8914744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Weill-Marchesani syndrome is a rare, generalized disorder of connective tissue manifested by short stature, brachymorphia, and spherophakia. Inheritance is autosomal recessive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6739588", "endSection": "abstract" } ] }, { "body": "Tumor-treating fields are effective for treatment of which cancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19133110", "http://www.ncbi.nlm.nih.gov/pubmed/23899985", "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "http://www.ncbi.nlm.nih.gov/pubmed/20492723", "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "http://www.ncbi.nlm.nih.gov/pubmed/19387848" ], "ideal_answer": [ "Clinical trials have shown that Tumor-treating fields are effective for treatment of non-small cell lung cancer and glioblastoma. Ongoing and future trials will evaluate TTFields in solid tumor brain metastases, and ovarian, pancreatic cancers and multidrug resistance cancer cells." ], "exact_answer": [ [ "non-small cell lung cancer" ], [ "glioblastoma" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812" ], "type": "list", "id": "56c1f007ef6e39474100003b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "endSection": "title" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1219, "text": "e evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1798, "text": "Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Response patterns of recurrent glioblastomas treated with tumor-treating fields.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "title" }, { "offsetInBeginSection": 293, "offsetInEndSection": 1152, "text": "NovoTTF Therapy is a novel and US Food and Drug Administration (FDA)-approved antimitotic treatment for recurrent GBM with potential benefits compared with other options. Recurrent GBM patients from two prior trials with demonstrated radiologic tumor response to single-agent NovoTTF Therapy were analyzed to better characterize tumor response patterns and evaluate the associations between response, compliance, and OS. In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields). The overall response rate across both trials was 15% (4% complete responses): 14% in the phase III trial (14/120) and 20% (2/10) in a pilot study. Tumor responses to NovoTTF Therapy developed slowly (median time to response, 5.2 months) but were durable (median duration, 12.9 months).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "abstract" }, { "offsetInBeginSection": 1645, "offsetInEndSection": 1807, "text": "NovoTTF Therapy is a novel antimitotic treatment for recurrent GBM associated with slowly developing but durable tumor responses in approximately 15% of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF\u2122-100A system.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 334, "text": " An ongoing trial is assessing its efficacy for newly diagnosed glioblastoma multiforme (GBM) and it has been FDA-approved for recurrent GBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 712, "text": "We present three patients with GBM in whom the fields were adjusted at recurrence and the effects of each adjustment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 975, "text": "The first patient underwent subtotal resection, radiotherapy with temozolomide (TMZ), and then began NovoTTF Therapy with metronomic TMZ. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1713, "text": " A second patient underwent two resections followed by radiotherapy/TMZ and NovoTTF Therapy/TMZ. Six months later, two new distal lesions were noted, and he underwent further resection with adjustment of his fields. He remained stable over the subsequent year on NovoTTF Therapy and bevacizumab. A third patient on NovoTTF Therapy/TMZ remained stable for two years but developed a small, slow growing enhancing lesion, which was resected, and his fields were adjusted accordingly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "title" }, { "offsetInBeginSection": 160, "offsetInEndSection": 466, "text": "Promising preclinical data have led to a single arm phase I/II trial in NSCLC patients.METHODS: Forty-two inoperable stage IIIB (with pleural effusion) and IV NSCLC patients who had had tumor progression received pemetrexed 500 mg/m(2) iv q3w together with daily TTFields therapy until disease progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 770, "text": "The median time to in-field progression was 28 weeks and the median time to systemic progression was 22 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1298, "text": "CONCLUSIONS: The combination of TTFields and pemetrexed as a second line therapy for NSCLC is safe and potentially more effective than pemetrexed alone. TTFields improved disease control within the treatment field and a phase III study is planned to further investigate its role as a novel treatment in NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment modality that has been approved for the treatment of recurrent glioblastoma by the U.S. FDA and has a CE mark in Europe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 1227, "text": "The antimitotic effect of TTFields therapy has been demonstrated in multiple cell lines when the appropriate frequency was utilized. A phase III trial of TTFields monotherapy compared to active chemotherapy in recurrent glioblastoma patients established that TTFields therapy is associated with minimal toxicity, better quality of life, and comparable efficacy to chemotherapy. Ongoing and future trials will evaluate TTFields in newly diagnosed glioblastoma, solid tumor brain metastases, nonsmall cell lung cancer, and ovarian and pancreatic cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 401, "text": "The U.S. Food and Drug Administration has approved the first device, the NovoTTF-100A\u2122, that uses this technology and is indicated for use in progressive glioblastoma multiforme after standard therapies have failed. Promising clinical trial results will likely lead to expanded uses in primary brain tumors and other cancer types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23899985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "endSection": "title" }, { "offsetInBeginSection": 336, "offsetInEndSection": 1080, "text": "Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. Our center was the first to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals in 2004 and 2005, and four of those original 20 patients are still alive today. We report two cases of GBM and two cases of RGBM treated by TTField therapy, all in good health and no longer receiving any treatment more than seven years after initiating TTField therapy, with no clinical or radiological evidence of recurrence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 349, "text": "Tumor treating fields (TTFields) are low intensity (1 ? 2 V/cm), intermediate frequency (100 ? 200 kHz) alternating electric fields administered using insulated electrodes placed on the skin surrounding the region of a malignant tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 1113, "text": "Furthermore, it summarizes the clinical experience with TTFields, mainly in two indications: one in recurrent glioblastoma multiforme: in a large prospective randomized Phase III trial TTFields was compared with best standard care (including chemotherapy): TTFields significantly improved median overall survival (OS) compared with standard therapy (7.8 vs 6.1 months) for the patients treated per protocol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1331, "text": "The second indication was a Phase II study in second-line non-small cell lung cancer, where TTFields was administered concomitantly with pemetrexed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract" }, { "offsetInBeginSection": 1546, "offsetInEndSection": 1711, "text": "EXPERT OPINION: The proof of concept of TTFields has been well demonstrated in the preclinical setting, and the clinical data seem promising in various tumor types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract" }, { "offsetInBeginSection": 1568, "offsetInEndSection": 1831, "text": "CONCLUSIONS: The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20492723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19387848", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19387848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "BACKGROUND: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19133110", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 847, "text": "In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients.RESULTS: The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19133110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "endSection": "title" }, { "offsetInBeginSection": 306, "offsetInEndSection": 555, "text": "PATIENTS AND METHODS: This open, prospective pilot study was designed to evaluate the safety, tolerability, and efficacy profile of TTFields treatment in patients with locally advanced and/or metastatic solid tumors using the NovoTTF100A(TM) device.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 1442, "text": "Outcomes showed 1 partial response of a treated skin metastasis from a primary breast cancer, 3 cases where tumor growth was arrested during treatment, and 1 case of disease progression. One mesothelioma patient experienced lesion regression near TTFields with simultaneous tumor stability or progression in distal areas.CONCLUSION: Although the number of patients in this study is small, the lack of therapy toxicity and the efficacy observed in data gathered to date indicate the potential of TTFields as a new treatment modality for solid tumors, definitely warranting further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "OBJECTIVES: Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. The present study determined the efficacy and mechanism of action of TTFields in preclinical models of pancreatic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 1371, "text": "RESULTS: Application of TTFields in vitro showed a significant decrease in cell count, an increase in cell volume and reduced clonogenicity. Further analysis demonstrated significant increase in the number of abnormal mitotic figures, as well as a decrease in G2-M cell population. In hamsters with orthotopic pancreatic tumors, TTFields significantly reduced tumor volume accompanied by an increase in the frequency of abnormal mitotic events. TTFields efficacy was enhanced both in vitro and in vivo when combined with chemotherapy.CONCLUSIONS: These results provide the first evidence that TTFields serve as an effective antimitotic treatment in preclinical pancreatic cancer models and have a long term negative effect on cancer cell survival. These results make TTFields an attractive candidate for testing in the treatment of patients with pancreatic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1013, "text": "In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 924, "text": "Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment modality that has been approved for the treatment of recurrent glioblastoma by the U.S. FDA and has a CE mark in Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 632, "text": "Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 867, "text": "In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "OBJECTIVES: Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "abstract" } ] }, { "body": "Which event results in the acetylation of S6K1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "http://www.ncbi.nlm.nih.gov/pubmed/19961954" ], "ideal_answer": [ "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation. We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling. Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300", "Acetylation of S6K1 and 2 is increased upon the inhibition of class I/II histone deacetylases (HDACs) by trichostatin-A, while the enhancement of S6K1 acetylation by nicotinamide suggests the additional involvement of sirtuin deacetylases in S6K deacetylationUsing acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation", "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling", "K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling, followed by interaction with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6K1 can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006473", "http://www.uniprot.org/uniprot/KS6B1_MOUSE", "http://www.uniprot.org/uniprot/KS6B1_BOVIN", "http://www.uniprot.org/uniprot/KS6B1_RAT", "http://www.uniprot.org/uniprot/KS6B1_HUMAN", "http://www.uniprot.org/uniprot/KS6B1_RABIT" ], "type": "summary", "id": "551173c26a8cde6b72000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "S6K1 is acetylated at lysine 516 in response to growth factor stimulation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "endSection": "title" }, { "offsetInBeginSection": 293, "offsetInEndSection": 396, "text": "In addition to phosphorylation, we have recently shown that S6K1 is also targeted by lysine acetylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 590, "text": "Here, using tandem mass spectrometry we have mapped acetylation of S6K1 to lysine 516, a site close to the C-terminus of the kinase that is highly conserved amongst vertebrate S6K1 orthologues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 738, "text": "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1215, "text": "We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Histone acetyltransferases interact with and acetylate p70 ribosomal S6 kinases in vitro and in vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961954", "endSection": "title" }, { "offsetInBeginSection": 404, "offsetInEndSection": 626, "text": "Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961954", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1033, "text": "Acetylation of S6K1 and 2 is increased upon the inhibition of class I/II histone deacetylases (HDACs) by trichostatin-A, while the enhancement of S6K1 acetylation by nicotinamide suggests the additional involvement of sirtuin deacetylases in S6K deacetylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961954", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 627, "text": "Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961954", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 773, "text": "Furthermore, it appears that the acetylation sites targeted by p300 lie within the divergent C-terminal regulatory domains of both S6K1 and S6K2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961954", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 771, "text": "Furthermore, it appears that the acetylation sites targeted by p300 lie within the divergent C-terminal regulatory domains of both S6K1 and S6K2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961954", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1216, "text": "We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "endSection": "abstract" } ] }, { "body": "List angiocrine factors", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21148069", "http://www.ncbi.nlm.nih.gov/pubmed/24018375", "http://www.ncbi.nlm.nih.gov/pubmed/24257808", "http://www.ncbi.nlm.nih.gov/pubmed/20094048", "http://www.ncbi.nlm.nih.gov/pubmed/21068842", "http://www.ncbi.nlm.nih.gov/pubmed/24257019" ], "ideal_answer": [ "Angiocrine factors are: Ccl4, neurotensin, vascular endothelial growth factor, metalloproteinases-1, thrombospondin 3, Slit2, hepatocyte growth factor, Wnt2. " ], "exact_answer": [ [ "Ccl4" ], [ "neurotensin" ], [ "vascular endothelial growth factor" ], [ "metalloproteinases-1" ], [ "thrombospondin 3" ], [ "Slit2" ], [ "hepatocyte growth factor" ], [ "Wnt2" ] ], "type": "list", "id": "56e46ad951531f7e3300001a", "snippets": [ { "offsetInBeginSection": 697, "offsetInEndSection": 744, "text": "Ccl4 and neurotensin (Nts) (angiocrine factors)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257808", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 838, "text": "vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24018375", "endSection": "abstract" }, { "offsetInBeginSection": 1628, "offsetInEndSection": 1726, "text": "angiocrine factors tissue inhibitor of metalloproteinases-1 (Timp-1) and thrombospondin 3 (THBS3) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257019", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 575, "text": "We found that Slit2, which is negatively regulated by endothelial EphA2 receptor, is one such tumor suppressive angiocrine factor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21148069", "endSection": "abstract" }, { "offsetInBeginSection": 1631, "offsetInEndSection": 1701, "text": "angiocrine factors, including hepatocyte growth factor (HGF) and Wnt2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21068842", "endSection": "abstract" } ] }, { "body": "What is protein carbamylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23335428", "http://www.ncbi.nlm.nih.gov/pubmed/24161613", "http://www.ncbi.nlm.nih.gov/pubmed/21235354", "http://www.ncbi.nlm.nih.gov/pubmed/25037561", "http://www.ncbi.nlm.nih.gov/pubmed/24056952", "http://www.ncbi.nlm.nih.gov/pubmed/24386107", "http://www.ncbi.nlm.nih.gov/pubmed/17828273", "http://www.ncbi.nlm.nih.gov/pubmed/24324801", "http://www.ncbi.nlm.nih.gov/pubmed/24900204", "http://www.ncbi.nlm.nih.gov/pubmed/21838543", "http://www.ncbi.nlm.nih.gov/pubmed/23582087", "http://www.ncbi.nlm.nih.gov/pubmed/23431074" ], "ideal_answer": [ "Protein carbamylation is a post-translational modification that can occur in the presence of urea. In solution, urea is in equilibrium with ammonium cyanate, and carbamylation occurs when cyanate ions react with the amino groups of lysines, arginines, protein N-termini, as well as sulfhydryl groups of cysteines. Protein carbamylation is one of the important post-translational modifications, which plays a pivotal role in a number of biological conditions, such as diseases, chronic renal failure and atherosclerosis." ], "type": "summary", "id": "56f82a39cf1c325851000001", "snippets": [ { "offsetInBeginSection": 158, "offsetInEndSection": 302, "text": "urea solution can cause carbamylation at the N termini of proteins/peptides and at the side chain amino groups of lysine and arginine residues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24161613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Carbamylation describes a nonenzymatic posttranslational protein modification mediated by cyanate, a dissociation product of urea. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25037561", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 290, "text": "Cyanate, a reactive electrophilic species in equilibrium with urea, posttranslationally modifies proteins through a process called carbamylation, which promotes atherosclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23431074", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 238, "text": "Protein carbamylation, a posttranslational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "Carbamylation (carbamoylation) of lysine residues and protein N-termini is a nonenzymatic PTM that has been related to protein ageing. In contrast to other PTM, such as phosphorylation, carbamylation can be artificially introduced during sample preparation with urea, thus affecting studies directed toward in vivo carbamylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23335428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Carbamylation is a general process involved in protein molecular ageing due to the nonenzymatic binding of isocyanic acid, mainly generated by urea dissociation, to free amino groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Protein carbamylation is one of the important post-translational modifications, which plays a pivotal role in a number of biological conditions, such as diseases, chronic renal failure and atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Protein carbamylation is a post-translational modification that can occur in the presence of urea. In solution, urea is in equilibrium with ammonium cyanate, and carbamylation occurs when cyanate ions react with the amino groups of lysines, arginines, protein N-termini, as well as sulfhydryl groups of cysteines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24386107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Carbamylation of proteins through reactive cyanate has been demonstrated to predict an increased cardiovascular risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21235354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Protein carbamylation is of great concern both in vivo and in vitro. Here, we report the first structural characterization of a protein carbamylated at the N-terminal proline. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Post-translational modification and functional impairment of proteins through carbamylation is thought to promote vascular dysfunction during end-stage renal disease. Cyanate, a reactive species in equilibrium with urea, carbamylates protein lysine residues to form epsilon-carbamyllysine (homocitrulline), altering protein structure and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17828273", "endSection": "abstract" } ] }, { "body": "What is the cause of episodic ataxia type 6?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23107647" ], "ideal_answer": [ "Episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1. Reduced glutamate uptake by mutant excitatory amino acid transporter-1 (EAAT1) has been thought to be the main pathophysiological process in episodic ataxia type 6." ], "exact_answer": [ "EAAT1 mutations" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:963" ], "type": "factoid", "id": "571e4293bb137a4b0c00000b", "snippets": [ { "offsetInBeginSection": 98, "offsetInEndSection": 497, "text": "There are several genetically and clinically distinct forms of this disease, and one of them, episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1. So far, reduced glutamate uptake by mutant excitatory amino acid transporter-1 has been thought to be the main pathophysiological process in episodic ataxia type 6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23107647", "endSection": "abstract" }, { "offsetInBeginSection": 1645, "offsetInEndSection": 1934, "text": "Episodic ataxia type 6 represents the first human disease found to be associated with altered function of excitatory amino acid transporter anion channels and illustrates possible physiological and pathophysiological impacts of this functional mode of this class of glutamate transporters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23107647", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 497, "text": "There are several genetically and clinically distinct forms of this disease, and one of them, episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1. So far, reduced glutamate uptake by mutant excitatory amino acid transporter-1 has been thought to be the main pathophysiological process in episodic ataxia type 6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23107647", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 332, "text": "There are several genetically and clinically distinct forms of this disease, and one of them, episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23107647", "endSection": "abstract" } ] }, { "body": "What is the main role of Ctf4 in dna replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "http://www.ncbi.nlm.nih.gov/pubmed/24255107", "http://www.ncbi.nlm.nih.gov/pubmed/20381454", "http://www.ncbi.nlm.nih.gov/pubmed/9199353", "http://www.ncbi.nlm.nih.gov/pubmed/17761813", "http://www.ncbi.nlm.nih.gov/pubmed/12455694", "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "http://www.ncbi.nlm.nih.gov/pubmed/19430531", "http://www.ncbi.nlm.nih.gov/pubmed/19805216", "http://www.ncbi.nlm.nih.gov/pubmed/20980819", "http://www.ncbi.nlm.nih.gov/pubmed/24805245", "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "http://www.ncbi.nlm.nih.gov/pubmed/19910927", "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "http://www.ncbi.nlm.nih.gov/pubmed/14742710", "http://www.ncbi.nlm.nih.gov/pubmed/1448101" ], "ideal_answer": [ "coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this processAnd-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery", "Ctf4 coordinates the progression of helicase and DNA polymerase alpha. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery." ], "exact_answer": [ "Coordination of the progression of helicase and DNA polymerase alpha at the eukaryotic replication fork." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045740", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006260", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006275", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008156" ], "type": "factoid", "id": "530cf22aa177c6630c000004", "snippets": [ { "offsetInBeginSection": 95, "offsetInEndSection": 351, "text": "In this report, interactions between human Ctf4 (hCtf4) and the replicative helicase containing the cell division cycle 45 (Cdc45)/minichromosome maintenance 2-7 (Mcm2-7)/Go, Ichi, Nii, and San (GINS) (CMG) proteins [human CMG (hCMG) complex] were examined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255107", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1130, "text": "We demonstrate that the hCtf4-CMG complex contains a homodimeric hCtf4 and a monomeric hCMG complex and suggest that the homodimeric hCtf4 acts as a platform linking polymerase \u03b1 to the hCMG complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "title" }, { "offsetInBeginSection": 246, "offsetInEndSection": 392, "text": "The Ctf4 protein has been shown to be a central member of the replication fork and links the replicative MCM helicase and DNA polymerase \u03b1 primase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 584, "text": " it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC), and as being important for sister chromatid cohesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 913, "text": "Drosophila Ctf4 is a conserved protein that interacts with members of the GINS complex, Mcm2, and Polymerase \u03b1 primase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1173, "text": "Ctf4 remains a central player in DNA replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1084, "text": "These data indicate that Ctf4p facilitates Mcm10p to promote the DNA replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20381454", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1050, "text": " hCtf4 plays an essential role in DNA replication and its ability to stimulate the replicative DNA polymerases ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 592, "text": "Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1119, "text": "coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Ctf4 coordinates the progression of helicase and DNA polymerase alpha", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17761813", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 433, "text": "We show that And-1/Ctf4 (Chromosome transmission fidelity 4) interacts with Mcm10, which associates with MCM2-7, and with the p180 subunit of DNA pol alpha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17761813", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 1125, "text": "And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17761813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17761813", "endSection": "title" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1131, "text": "Ctf4 remains a central player in DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Influence of the human cohesion establishment factor Ctf4/AND-1 on DNA replication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 250, "text": "In this report, we examined the mechanism of action of human Ctf4 (hCtf4) in DNA replication both in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1120, "text": "And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17761813", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 909, "text": "We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1083, "text": "Using in vivo RNAi knockdown of CTF4 in Drosophila we show that Ctf4 is required for viability, S phase progression, sister chromatid cohesion, endoreplication, and coping with replication stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "abstract" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1480, "text": "We show that Ctf4 function is conserved and that Drosophila can be effectively used as a model to further probe the precise function of Ctf4 as a member of the replication fork and possible roles in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Chromosome transmission fidelity 4 (Ctf4) is a conserved protein required for DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255107", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 626, "text": "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "title" } ] }, { "body": "Could Arimidex (anastrozole) cause hot flashes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21378354", "http://www.ncbi.nlm.nih.gov/pubmed/23452648", "http://www.ncbi.nlm.nih.gov/pubmed/17292609", "http://www.ncbi.nlm.nih.gov/pubmed/20975874", "http://www.ncbi.nlm.nih.gov/pubmed/20679610", "http://www.ncbi.nlm.nih.gov/pubmed/15494636", "http://www.ncbi.nlm.nih.gov/pubmed/14584060", "http://www.ncbi.nlm.nih.gov/pubmed/14675683", "http://www.ncbi.nlm.nih.gov/pubmed/18072256", "http://www.ncbi.nlm.nih.gov/pubmed/18728707", "http://www.ncbi.nlm.nih.gov/pubmed/12902876", "http://www.ncbi.nlm.nih.gov/pubmed/23314924", "http://www.ncbi.nlm.nih.gov/pubmed/23383974", "http://www.ncbi.nlm.nih.gov/pubmed/22677000", "http://www.ncbi.nlm.nih.gov/pubmed/22370325", "http://www.ncbi.nlm.nih.gov/pubmed/15508444" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10338338", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0878174", "o": "http://linkedlifedata.com/resource/umls/label/A11917539" } ], "ideal_answer": [ "Yes. Hot flashes are one of the most common adverse effects of Arimidex." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019584", "http://www.biosemantics.org/jochem#4266381", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006358" ], "type": "yesno", "id": "516523fd298dcd4e51000055", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "More than a third of breast cancer patients undergoing aromatase inhibitor (AI) treatment report joint pain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452648", "endSection": "sections.0" }, { "offsetInBeginSection": 789, "offsetInEndSection": 967, "text": "In the first 6 weeks, emergence of joint pain was associated with increase in general pain, fatigue, disturbed sleep, hot flashes, vaginal dryness, and decreased sexual activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452648", "endSection": "sections.0" }, { "offsetInBeginSection": 21, "offsetInEndSection": 138, "text": "Antiestrogen therapy can cause vasomotor symptoms similar to those occurring during menopause, including hot flashes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23383974", "endSection": "sections.0" }, { "offsetInBeginSection": 275, "offsetInEndSection": 455, "text": "The purpose of this study was to assess the feasibility and safety of acupuncture for treatment of hot flashes in Korean patients with breast cancer receiving antiestrogen therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23383974", "endSection": "sections.0" }, { "offsetInBeginSection": 715, "offsetInEndSection": 857, "text": "10 patients with breast cancer who were undergoing antiestrogen therapy with tamoxifen or anastrozole and who were suffering from hot flashes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23383974", "endSection": "sections.0" }, { "offsetInBeginSection": 1118, "offsetInEndSection": 1199, "text": "During treatment, severity of hot flashes was reduced by 70%-95% in all patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23383974", "endSection": "sections.0" }, { "offsetInBeginSection": 59, "offsetInEndSection": 188, "text": "anastrozole has been widely used in Japan as an adjuvant treatment for postmenopausal, hormone-responsive breast cancer patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314924", "endSection": "sections.0" }, { "offsetInBeginSection": 291, "offsetInEndSection": 435, "text": "The aim of this study is to evaluate the rate of bone fracture and bone mineral density (BMD) during anastrozole treatment in Japanese patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314924", "endSection": "sections.0" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1177, "text": "Musculoskeletal disorders were the most common (26.1\u00a0%), and hot flashes were the second most common adverse event (7.9\u00a0%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314924", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 177, "text": "To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370325", "endSection": "sections.0" }, { "offsetInBeginSection": 455, "offsetInEndSection": 592, "text": "fulvestrant loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370325", "endSection": "sections.0" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1373, "text": "Incidences of prespecified adverse events (AEs) were similar. Hot flashes were more common in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the standard arm (P = .0023).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370325", "endSection": "sections.0" }, { "offsetInBeginSection": 414, "offsetInEndSection": 602, "text": "The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22677000", "endSection": "sections.0" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1181, "text": "AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22677000", "endSection": "sections.0" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1520, "text": "Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22677000", "endSection": "sections.0" }, { "offsetInBeginSection": 342, "offsetInEndSection": 571, "text": "Twenty-five PM-BC patients received, in sequence, leuprorelin, taxane-anthracycline induction chemotherapy, radiation therapy, a platinum-based intensification high-dose CT, followed by leuprorelin and anastrazole for five years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21378354", "endSection": "sections.0" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1143, "text": "Grade 4 hematologic toxicity was observed in all patients, no patient showed a decrease of cardiac ejection fraction and hot flashes and arthralgias were of moderate intensity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21378354", "endSection": "sections.0" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1826, "text": "Of the patients treated with anastrozole, 3 (37.5%) reported toxicity, with 1 report each of decreased libido, leg swelling, and depression (12.5%). Toxicity was reported in 2 patients taking letrozole (40%), with both reporting peripheral edema, and 1 reporting hot flashes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20975874", "endSection": "sections.0" }, { "offsetInBeginSection": 507, "offsetInEndSection": 652, "text": "Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20679610", "endSection": "sections.0" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1369, "text": "The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20679610", "endSection": "sections.0" }, { "offsetInBeginSection": 319, "offsetInEndSection": 553, "text": "These studies were designed to evaluate the safety and efficacy of AIs in the following clinical settings: 1) as initial adjuvant therapy (the Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group Trial 1-98),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18072256", "endSection": "sections.0" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1274, "text": "AIs were tolerated well, and patients who received them experienced fewer thrombolic events and less endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with patients who receive tamoxifen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18072256", "endSection": "sections.0" }, { "offsetInBeginSection": 238, "offsetInEndSection": 523, "text": "It has been suggested that the association of AI and GnRh analogues and AI could block the two routes of oestrogen production in males, and therefore this approach could increase efficacy. However, it could also enhance the rate of adverse events (hot flashes, sexual impotence, etc.).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17292609", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "We reviewed therapeutic effects and harmful side effects in 33 patients with advanced or recurrent breast cancer who underwent treatment with Anastrozole 1 mg/day in our department.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15508444", "endSection": "sections.0" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1527, "text": "The most frequent harmful side effects were rise in total cholesterol, general fatigue, hot flashes and arthralgia (9.1%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15508444", "endSection": "sections.0" }, { "offsetInBeginSection": 151, "offsetInEndSection": 330, "text": "We analyzed the changes in frequency and severity of menopausal symptoms in patients receiving tamoxifen or aromatase inhibitors and identified factors influencing these symptoms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15494636", "endSection": "sections.0" }, { "offsetInBeginSection": 662, "offsetInEndSection": 816, "text": "Both first-line tamoxifen and aromatase inhibitors induced an increase in the occurrence and severity of hot flashes (p<0.0001 and p=0.014, respectively).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15494636", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 208, "text": "To evaluate the efficacy and toxicity of the selective aromatase inhibitor anastrozole (Arimidex), we conducted a phase II trial in 53 women with asymptomatic recurrent/persistent m\u00fcllerian cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14675683", "endSection": "sections.0" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1615, "text": "Toxicity was modest (grade I) and infrequent, with the most common toxicities being fatigue and hot flashes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14675683", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 390, "text": "The first analysis of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial (median follow-up, 33 months) demonstrated that in adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer, anastrozole was superior to tamoxifen in terms of disease-free survival (DFS), time to recurrence (TTR), and incidence of contralateral breast cancer (CLBC).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14584060", "endSection": "sections.0" }, { "offsetInBeginSection": 1813, "offsetInEndSection": 2194, "text": "in that endometrial cancer (P = 0.007), vaginal bleeding and discharge (P < 0.001 for both), cerebrovascular events (P < 0.001), venous thromboembolic events (P < 0.001), and hot flashes (P < 0.001) all occurred less frequently in the anastrozole group, whereas musculoskeletal disorders and fractures (P < 0.001 for both) continued to occur less frequently in the tamoxifen group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14584060", "endSection": "sections.0" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1173, "text": "reduced nausea, hot flashes, and abdominal discomfort caused almost twice as many patients to prefer to continue with letrozole therapy than with anastrozole", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12902876", "endSection": "sections.0" } ] }, { "body": "What is the role of Inn1 in cytokinesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "http://www.ncbi.nlm.nih.gov/pubmed/22454527", "http://www.ncbi.nlm.nih.gov/pubmed/20442249", "http://www.ncbi.nlm.nih.gov/pubmed/19707790", "http://www.ncbi.nlm.nih.gov/pubmed/19528296", "http://www.ncbi.nlm.nih.gov/pubmed/18344988" ], "ideal_answer": [ "Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane during cytokinesis in budding yeast, whereas the remainder of the protein recruits Inn1 to the actomyosin ring" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000910", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048749", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032466", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032467", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032465" ], "type": "summary", "id": "530cf22aa177c6630c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "endSection": "title" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1334, "text": "Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Cdc14-dependent dephosphorylation of Inn1 contributes to Inn1-Cyk3 complex formation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454527", "endSection": "title" }, { "offsetInBeginSection": 488, "offsetInEndSection": 975, "text": "Cdc14 colocalizes with Inn1 at the cell division site and interacts with the C-terminal proline-rich domain of Inn1 that mediates its binding to the SH3-domain-containing proteins Hof1 and Cyk3. We show that phosphorylation of Inn1 by Cdk1 partially perturbs the interaction of Inn1 with Cyk3 thereby reducing the levels of Cyk3 at the cell division site. We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442249", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Cyk3 acts in actomyosin ring independent cytokinesis by recruiting Inn1 to the yeast bud neck", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707790", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19528296", "endSection": "title" }, { "offsetInBeginSection": 87, "offsetInEndSection": 442, "text": "we identified a novel factor that we call Inn1, which associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. We show that Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane, whereas the remainder of the protein recruits Inn1 to the actomyosin ring", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18344988", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 837, "text": " Our data indicate that recruitment of the C2 domain of Inn1 to the contractile actomyosin ring is crucial for ingression of the plasma membrane during cytokinesis in budding yeast", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18344988", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 329, "text": "We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 971, "text": "We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Cyk3 acts in actomyosin ring independent cytokinesis by recruiting Inn1 to the yeast bud neck.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707790", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Inn1 couples contraction of the actomyosin ring to membrane ingression during cytokinesis in budding yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18344988", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442249", "endSection": "title" }, { "offsetInBeginSection": 877, "offsetInEndSection": 995, "text": "We therefore propose that the MEN directly controls cytokinesis via targeting of Inn1, Cyk3 and Chs2 to the bud neck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442249", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1326, "text": "Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1180, "text": "In addition to compensating for mutations in the Inn1 C2-domain, the dominant CHS2 alleles suppress cytokinesis defects produced by the lack of the Cyk3 protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1171, "text": "We propose that Cyk3 is part of an actomyosin ring independent cytokinesis pathway, which acts as a rescue mechanism to recruit Inn1 to the bud neck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707790", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 330, "text": "We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1179, "text": "We propose that Cyk3 is part of an actomyosin ring independent cytokinesis pathway, which acts as a rescue mechanism to recruit Inn1 to the bud neck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707790", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 707, "text": "The Inn1 C-terminal region is necessary for localization, and distinct PXXP motifs in this region mediate functionally important interactions with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore PS formation in inn1Delta cells).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19528296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19528296", "endSection": "title" }, { "offsetInBeginSection": 844, "offsetInEndSection": 976, "text": "We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454527", "endSection": "abstract" } ] }, { "body": "Which hormone deficiency is implicated in the Costello syndrome ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15940703", "http://www.ncbi.nlm.nih.gov/pubmed/18483625", "http://www.ncbi.nlm.nih.gov/pubmed/17551924", "http://www.ncbi.nlm.nih.gov/pubmed/22752028", "http://www.ncbi.nlm.nih.gov/pubmed/22887473", "http://www.ncbi.nlm.nih.gov/pubmed/16278907", "http://www.ncbi.nlm.nih.gov/pubmed/20307337", "http://www.ncbi.nlm.nih.gov/pubmed/22821884", "http://www.ncbi.nlm.nih.gov/pubmed/14564166", "http://www.ncbi.nlm.nih.gov/pubmed/19035362", "http://www.ncbi.nlm.nih.gov/pubmed/15316968", "http://www.ncbi.nlm.nih.gov/pubmed/21438134", "http://www.ncbi.nlm.nih.gov/pubmed/15316966", "http://www.ncbi.nlm.nih.gov/pubmed/8168845", "http://www.ncbi.nlm.nih.gov/pubmed/19258709" ], "ideal_answer": [ "Growth hormone deficiency is implicated in Costello syndrome. Growth hormone therapy should be administered with caution due to possible severe side effects. Cortisol and sex hormone deficiencies were also implicated in Costello syndrome." ], "exact_answer": [ "Growth hormone deficiency" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056685", "http://www.disease-ontology.org/api/metadata/DOID:0050469", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006728" ], "type": "factoid", "id": "53130a77e3eabad02100000f", "snippets": [ { "offsetInBeginSection": 1019, "offsetInEndSection": 1120, "text": "Measurements obtained after growth hormone exposure in 15 individuals were excluded in this analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22887473", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1001, "text": "Furthermore, we observed that RasGRF1 becomes phosphorylated in ARMS after stimulation by several pro-metastatic factors, such as SDF-1 and HGF/SF, as well as after exposure to growth-promoting Igf-2 and insulin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22752028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Progressively worsening hypertrophic cardiomyopathy in a child with newly diagnosed Costello syndrome while receiving growth hormone therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20307337", "endSection": "title" }, { "offsetInBeginSection": 235, "offsetInEndSection": 458, "text": "This report highlights two important concepts: the association of genetic syndromes with hypertrophic cardiomyopathy and the possibility of worsening severity of hypertrophic cardiomyopathy linked to growth hormone therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20307337", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Oncogenic HRAS mutations cause prolonged PI3K signaling in response to epidermal growth factor in fibroblasts of patients with Costello syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19035362", "endSection": "title" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1291, "text": "Statistical significance was achieved, despite the relatively small number of patients with BRAF and MEK1 mutations reported here, for polyhydramnios, growth hormone deficiency and the presence of more than one papilloma, which were less common in CFC compared to HRAS mutation positive patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17551924", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 503, "text": "Endocrine abnormalities including growth hormone deficiency, adrenal insufficiency, glucose intolerance, parathyroid adenoma with hyperprolactinemia and hypoglycemia have been described. Hypoglycemia has been documented due to growth hormone and cortisol deficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16278907", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 468, "text": "Endocrine problems in this series were osteoporosis, central hypogonadism, and delayed puberty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15940703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Growth hormone deficiency in Costello syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316968", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 458, "text": "We report on three patients with Costello syndrome and isolated growth hormone (GH) deficiency treated with biosynthetic GH. To our knowledge, these are the only patients with Costello syndrome who have been successfully treated for GH deficiency. We review the pathophysiology of Costello syndrome and highlight the recent recommendations of tumor screening and cardiac surveillance in this population, of particular relevance to those receiving GH therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Costello syndrome with growth hormone deficiency and hypoglycemia: a new report and review of the endocrine associations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316966", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "We describe an 18-month-old boy with Costello syndrome (CS) with proven partial growth hormone (GH) deficiency and hypoglycemic episodes. The hypoglycemia is deemed to be due to cortisol deficiency. This report represents the second published case of cortisol deficiency in the CS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "We present the case of a boy with Costello syndrome who developed osteofibrous dysplasia during a phase of growth hormone therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14564166", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 520, "text": "Thus, although osteofibrous dysplasia in Costello syndrome has not been reported before, growth hormone therapy should be used under close supervision in children with this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14564166", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 412, "text": "Endocrinological investigations revealed a partial deficiency of growth hormone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8168845", "endSection": "abstract" } ] }, { "body": "List the components of a Replisome Progression Complex (RPC).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22918584", "http://www.ncbi.nlm.nih.gov/pubmed/16930479", "http://www.ncbi.nlm.nih.gov/pubmed/16531994", "http://www.ncbi.nlm.nih.gov/pubmed/23499444", "http://www.ncbi.nlm.nih.gov/pubmed/21701592", "http://www.ncbi.nlm.nih.gov/pubmed/19913425", "http://www.ncbi.nlm.nih.gov/pubmed/21505101", "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "http://www.ncbi.nlm.nih.gov/pubmed/19910927", "http://www.ncbi.nlm.nih.gov/pubmed/16483939", "http://www.ncbi.nlm.nih.gov/pubmed/19622120" ], "ideal_answer": [ "RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I.", "RPCs also interact with Mcm10 and topoisomerase I. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs. This interaction requires the RPC components Mrc1 and Ctf4, both of which associate with a tetratricopeptide repeat (TPR) domain located at the amino terminus of Dia2. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. " ], "exact_answer": [ [ "Cdc45" ], [ "Mrc1" ], [ "Tof1-Csm3 complex" ], [ "FACT" ], [ "Ctf4" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030894" ], "type": "list", "id": "530cf22aa177c6630c000005", "snippets": [ { "offsetInBeginSection": 540, "offsetInEndSection": 706, "text": "This interaction requires the RPC components Mrc1 and Ctf4, both of which associate with a tetratricopeptide repeat (TPR) domain located at the amino terminus of Dia2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19913425", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 534, "text": "Here we show that SCF(Dia2) associates with the replisome progression complex (RPC) that assembles around the MCM2-7 helicase at DNA replication forks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19913425", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 332, "text": "We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 592, "text": "Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 742, "text": "Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 424, "text": "we show that the GINS (go ichi ni san) complex allows the MCM (minichromosome maintenance) helicase to interact with key regulatory proteins in large replisome progression complexes (RPCs) that are assembled during initiation and disassembled at the end of S phase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16531994", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 796, "text": "RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16531994", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1081, "text": "During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16531994", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 332, "text": "We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 537, "text": "Here we show that SCF(Dia2) associates with the replisome progression complex (RPC) that assembles around the MCM2-7 helicase at DNA replication forks [6].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19913425", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 821, "text": "Compared with wild type, hydroxyurea-treated ctf18\u0436\u0434 cells exhibited increased chromatin association of replisome progression complex components including Cdc45, Ctf4, and GINS complex subunits, the polymerase processivity clamp PCNA and the single-stranded DNA-binding complex RPA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The amino-terminal TPR domain of Dia2 tethers SCF(Dia2) to the replisome progression complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19913425", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Ctf4 is a protein conserved in eukaryotes and a constituent of the replisome progression complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 540, "text": "Eukaryotic GINS also links with other key proteins at the fork to maintain an active replisome progression complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918584", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 345, "text": "Dia2 has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21701592", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 966, "text": "The Cdc45-MCM-GINS complex could constitute the core of a larger macromolecular structure that has been termed the \"replisome progression complex\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16930479", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 706, "text": "FACT does not associate with the Mcm2-7 helicase at replication origins during G1 phase but is subsequently incorporated into the replisome progression complex independently of histone binding and uniquely among histone chaperones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23499444", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 590, "text": "Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Replisome progression complex links DNA replication to sister chromatid cohesion in Xenopus egg extracts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622120", "endSection": "title" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1032, "text": "On the basis of the physical interactions between AND-1 and DNA polymerases, we discuss a model to describe how replisome progression complex establishes sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The components of the replisome that preserve genomic stability by controlling the progression of eukaryotic DNA replication forks are poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16531994", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 746, "text": "RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16531994", "endSection": "abstract" } ] }, { "body": "What is the definition of minimal absent words?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19426495", "http://www.ncbi.nlm.nih.gov/pubmed/22974263", "http://www.ncbi.nlm.nih.gov/pubmed/25526884" ], "ideal_answer": [ "An absent word of a word y of length n is a word that does not occur in y. It is a minimal absent word if all its proper factors occur in y. Minimal absent words have been computed in genomes of organisms from all domains of life; their computation also provides a fast alternative for measuring approximation in sequence comparison." ], "type": "summary", "id": "56acda7c0a360a5e45000005", "snippets": [ { "offsetInBeginSection": 336, "offsetInEndSection": 761, "text": " We show how absent words relate to the repetitions and structure of the data, and define a new and larger class of absent words, called minimal absent words, that still captures the essential properties of the shortest absent words introduced in recent works. The words of this new class are minimal in the sense that if their leftmost or rightmost character is removed, then the resulting word is no longer an absent word. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19426495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "An absent word (also called a forbidden word or an unword in other contexts) in a sequence is a segment that does not appear in the given sequence. It is a minimal absent word if all its proper factors occur in the given sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22974263", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 345, "text": "An absent word of a word y of length n is a word that does not occur in y. It is a minimal absent word if all its proper factors occur in y. Minimal absent words have been computed in genomes of organisms from all domains of life; their computation also provides a fast alternative for measuring approximation in sequence comparison.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25526884", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 742, "text": " We show how absent words relate to the repetitions and structure of the data, and define a new and larger class of absent words, called minimal absent words, that still captures the essential properties of the shortest absent words introduced in recent works. The words of this new class are minimal in the sense that if their leftmost or rightmost character is removed, then the resulting word is no longer an absent word.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19426495", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 742, "text": "We show how absent words relate to the repetitions and structure of the data, and define a new and larger class of absent words, called minimal absent words, that still captures the essential properties of the shortest absent words introduced in recent works. The words of this new class are minimal in the sense that if their leftmost or rightmost character is removed, then the resulting word is no longer an absent word.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19426495", "endSection": "abstract" } ] }, { "body": "What is the common feature in congenital central hypoventilation and Mowat-Wilson syndromes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "http://www.ncbi.nlm.nih.gov/pubmed/17397038" ], "ideal_answer": [ "About 30% of Hirschsprung disease (HSCR) cases are syndromic. Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS).", "In CCHS patients, the weak predisposing haplotype of the RET gene can be regarded as a quantitative trait, being a risk factor for the HSCR phenotype, while in MWS, for which the HSCR penetrance is high, the role of the RET predisposing haplotype is not significant." ], "type": "summary", "id": "55167dec46478f2f2c00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 982, "text": "Hirschsprung's disease (HSCR) is a fairly frequent cause of intestinal obstruction in children. It is characterized as a sex-linked heterogonous disorder with variable severity and incomplete penetrance giving rise to a variable pattern of inheritance. Although Hirschsprung's disease occurs as an isolated phenotype in at least 70% of cases, it is not infrequently associated with a number of congenital abnormalities and associated syndromes, demonstrating a spectrum of congenital anomalies. Certain of these syndromic phenotypes have been linked to distinct genetic sites, indicating underlying genetic associations of the disease and probable gene-gene interaction, in its pathogenesis. These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 879, "text": "On the other hand, about 30% of HSCR are syndromic. Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 642, "text": "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 764, "text": "The RET locus was genotyped in 143 CCHS patients, among whom 44 had HSCR, and in 30 MWS patients, among whom 20 had HSCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1077, "text": "RET was shown to act as a modifier gene for the HSCR phenotype in patients with CCHS but not with MWS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 982, "text": "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 880, "text": "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 643, "text": "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1078, "text": "RET was shown to act as a modifier gene for the HSCR phenotype in patients with CCHS but not with MWS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1558, "text": "In CCHS patients, the weak predisposing haplotype of the RET gene can be regarded as a quantitative trait, being a risk factor for the HSCR phenotype, while in MWS, for which the HSCR penetrance is high, the role of the RET predisposing haplotype is not significant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 979, "text": "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 874, "text": "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 606, "text": "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 980, "text": "These associations with HSCR include Downs syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 642, "text": "METHODS: The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 983, "text": "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 878, "text": "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 981, "text": "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "endSection": "abstract" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1791, "text": "The frequent, low penetrant, predisposing allele of the RET gene can be regarded as a risk factor for the HSCR phenotype in CCHS, BBS, and Down syndrome, while its role is not significant in MWS and WS4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1587, "text": "RET acts as a modifier gene for the HSCR phenotype in patients with CCHS, BBS, and Down syndrome, but not in patients with MWS and WS4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 612, "text": "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 879, "text": "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" }, { "offsetInBeginSection": 1794, "offsetInEndSection": 1884, "text": "These data highlight the pivotal role of the RET gene in both isolated and syndromic HSCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "endSection": "abstract" } ] }, { "body": "Which is the most common CFTR mutation in Caucasians?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11014930", "http://www.ncbi.nlm.nih.gov/pubmed/8222279", "http://www.ncbi.nlm.nih.gov/pubmed/1376017", "http://www.ncbi.nlm.nih.gov/pubmed/19837664", "http://www.ncbi.nlm.nih.gov/pubmed/8825494", "http://www.ncbi.nlm.nih.gov/pubmed/24517344", "http://www.ncbi.nlm.nih.gov/pubmed/23148214", "http://www.ncbi.nlm.nih.gov/pubmed/22081250", "http://www.ncbi.nlm.nih.gov/pubmed/12357328", "http://www.ncbi.nlm.nih.gov/pubmed/17662673" ], "ideal_answer": [ "The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4)." ], "exact_answer": [ "deltaF508" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003550", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801" ], "type": "factoid", "id": "56c5feb75795f9a73e000006", "snippets": [ { "offsetInBeginSection": 1382, "offsetInEndSection": 1497, "text": "Exposure to WCS caused a pronounced reduction in CFTR activity in both CFTR (+/+) cells and F508del CFTR (+/-) cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517344", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1096, "text": "Moreover, the common heterozygous F508del/5T and F508del/R117H were observed in 17 and 4% of CBAVD cases respectively, and the allele frequency in CBAVD was 17% for F508del, 25% for 5T and 3% for R117H.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081250", "endSection": "abstract" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1785, "text": "The most common mutations were p.F508del (DeltaF508) (18.1%), c.2183_2184delAAinsG (2183AA>G) (6.5%), p.S466X (5.8%), p.N1303K (4.3%), c.2789+5G>A (4.3%), p.G542X (3.6%), c.3120+1G>A (3.6%), p.R334W (2.9%) and c.3130delA (2.9%). These 9 types of mutant CFTR genes totaled for 52% of all CFTR genes derived from the 69 Iranian CF patients. Eight mutations, c.406-8T>C, p.A566D, c.2576delA, c.2752-1_2756delGGTGGCinsTTG, p.T1036I, p.W1145R, c.3850-24G>A, c.1342-?_1524+?del, were found for the first time in this study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662673", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 1116, "text": "The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12357328", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 561, "text": "Although the major mutation that results in a single amino acid deletion (F508) accounts for 70% of the disease alleles, more than 550 additional mutant alleles of different forms have been detected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8825494", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 678, "text": "Besides the major 3-bp deletion, delta F508 that was found on 73% of German CF chromosomes, more than 50 other missense, nonsense, frame-shift, and splice-site mutations have already been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8222279", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 660, "text": "However, the CFTR mutation delta F508 is the most common reason for the frequently inherited disease among the Caucasian population. Maturation and processing of delta F508-CFTR is defective which leads to expression of only very little but functional CFTR in the cell membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11014930", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1151, "text": "The most common disease-causing mutation, DeltaF508, is found in 70% of patients with cystic fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19837664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": " Cystic fibrosis is the most common inherited lethal disease in Caucasians. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), of which the cftr \u0394F508 mutation is the most common.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23148214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Cystic fibrosis is the most common inherited lethal disease in Caucasians. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), of which the cftr \u0394F508 mutation is the most common.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23148214", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1196, "text": "Caucasians (eight of nine), Northern Irish (four of five), and Israelis (three of three) also occurred in other Caucasian groups. The preponderance of previously reported mutations in these three groups suggested that a subset of the non-delta F508 mutations occur in common among Caucasians.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1376017", "endSection": "abstract" } ] }, { "body": "Which CDK targets control cytokinesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25371407" ], "ideal_answer": [ "Aip1, Ede1 and Inn1 are CDK targets whose dephosphorylation is required for cytokinesis." ], "exact_answer": [ [ "Aip1" ], [ "Ede1" ], [ "Inn1" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048749", "http://amigo.geneontology.org/amigo/term/GO:0032465", "http://amigo.geneontology.org/amigo/term/GO:0000910", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018844" ], "type": "list", "id": "56bf487def6e394741000011", "snippets": [ { "offsetInBeginSection": 464, "offsetInEndSection": 1093, "text": "We use phosphoproteome analysis of mitotic exit to identify Cdk targets that are dephosphorylated at the time of cytokinesis. We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis. This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators. Our results suggest that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25371407", "endSection": "abstract" } ] }, { "body": "Are Alu elements transcribed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7528809", "http://www.ncbi.nlm.nih.gov/pubmed/8093066", "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "http://www.ncbi.nlm.nih.gov/pubmed/22716230", "http://www.ncbi.nlm.nih.gov/pubmed/1709156", "http://www.ncbi.nlm.nih.gov/pubmed/8366099", "http://www.ncbi.nlm.nih.gov/pubmed/16682445", "http://www.ncbi.nlm.nih.gov/pubmed/15342557", "http://www.ncbi.nlm.nih.gov/pubmed/21987713", "http://www.ncbi.nlm.nih.gov/pubmed/6173130", "http://www.ncbi.nlm.nih.gov/pubmed/20424511", "http://www.ncbi.nlm.nih.gov/pubmed/2415825", "http://www.ncbi.nlm.nih.gov/pubmed/1704372", "http://www.ncbi.nlm.nih.gov/pubmed/15593371" ], "ideal_answer": [ "A significant percentage of the more than 1 million copies of Alu elements was shown to be transrcribed. Free Alu RNAs are known to be transcribed by Pol III from their own promoter. On the other hand, embedded Alu RNAs are transcribed by Pol II as part of protein- and non-protein-coding RNAs. Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression." ], "exact_answer": "yes", "type": "yesno", "id": "54dcd8f61388e8454a000001", "snippets": [ { "offsetInBeginSection": 15, "offsetInEndSection": 50, "text": "Alu RNAs in the human transcriptome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "endSection": "title" }, { "offsetInBeginSection": 179, "offsetInEndSection": 264, "text": "Alu elements can be transcribed in two different ways, by two independent polymerases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 332, "text": "'Free Alu RNAs' are transcribed by Pol III from their own promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 433, "text": "'embedded Alu RNAs' are transcribed by Pol II as part of protein- and non-protein-coding RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 576, "text": "Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 355, "text": "Alu RNAs transcribed from these elements are present at low levels at normal cell growth but various stress conditions increase their abundance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682445", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 412, "text": "Alu RNAs are known to bind the cognate proteins SRP9/14", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15593371", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 411, "text": "we used primer extension analysis to determine the level of polymerase III directed Alu RNA and found an increased expression of Alu RNA in hepatocellular carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15593371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Widespread RNA editing of embedded alu elements in the human transcriptome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342557", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 282, "text": "Transcribed Alu sequences can alter splicing patterns by generating new exons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342557", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 950, "text": "In the vast majority of edited RNAs, A-to-I substitutions are clustered within transcribed sense or antisense Alu sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342557", "endSection": "abstract" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1209, "text": "Alu-associated RNA editing may be a mechanism for marking nonstandard transcripts, not destined for translation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342557", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 80, "text": "the case of transcribed Alus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21987713", "endSection": "title" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1129, "text": "Differential levels of Alu RNA during different conditions of stress also await clear functional understanding", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21987713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Alu expression in human cell lines and their retrotranspositional potential", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22716230", "endSection": "title" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1196, "text": "Alu expression likely varies by cell type, growth conditions and transformation state", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22716230", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1560, "text": "The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22716230", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1263, "text": "We suggest that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2415825", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1383, "text": "These similarities suggest that some Alu family sequences are mobile genetic elements that can transpose to new chromosomal loci using as an intermediate a cDNA copy of an RNA transcribed from the Alu family element by RNA polymerase III.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6173130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Primate and rodent genomes are populated with hundreds of thousands copies of Alu and B1 elements dispersed by retroposition, i.e., by genomic reintegration of their reverse transcribed RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7528809", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 254, "text": "Members of this family are readily transcribed in vitro by RNA polymerase III, but RNA corresponding to only a small sub-set of Alu elements has been found in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8093066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Alu interspersed repetitive elements possess internal RNA polymerase III promoters which are strongly transcribed in vitro, yet these elements are nearly silent in somatic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8366099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The amplification of genomic Alu elements by retroposition, i.e. by reintegration of reverse-transcribed RNA, suggests that Alu RNA plays an important role in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1709156", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 303, "text": "We report enzymatic studies of the secondary structure of Alu RNAs transcribed in vitro from two recently retroposed Alu elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1709156", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1262, "text": "The results of this study indicate that Alu and 7SL RNA gene sequences interact with cellular factors that are important for HeLa cell proliferation and suggest that these pol III-transcribed elements may be involved in the regulation of cellular growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1704372", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 410, "text": "Then we used primer extension analysis to determine the level of polymerase III directed Alu RNA and found an increased expression of Alu RNA in hepatocellular carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15593371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Alu interspersed repetitive elements possess internal RNA polymerase III promoters which are strongly transcribed in vitro, yet these elements are nearly silent in somatic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8366099", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 433, "text": "'Free Alu RNAs' are transcribed by Pol III from their own promoter, while 'embedded Alu RNAs' are transcribed by Pol II as part of protein- and non-protein-coding RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 302, "text": "We report enzymatic studies of the secondary structure of Alu RNAs transcribed in vitro from two recently retroposed Alu elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1709156", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 369, "text": "Transcribed Alu sequences can alter splicing patterns by generating new exons, but other impacts of intragenic Alu elements on their host RNA are largely unexplored", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342557", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 459, "text": "Both 7SL genes and Alu elements are transcribed by RNA polymerase III, and we show here that the internal 7SL promoter lies within the Alu-like part of the 7SL gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2415825", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1317, "text": "Each group revealed a divergent pattern of transcribed Alu elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20424511", "endSection": "abstract" } ] }, { "body": "In what type(s) of plant organelles we can detect prolamellar bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24232321", "http://www.ncbi.nlm.nih.gov/pubmed/23415648", "http://www.ncbi.nlm.nih.gov/pubmed/22704664", "http://www.ncbi.nlm.nih.gov/pubmed/24151298", "http://www.ncbi.nlm.nih.gov/pubmed/18071923", "http://www.ncbi.nlm.nih.gov/pubmed/12602886", "http://www.ncbi.nlm.nih.gov/pubmed/11532175", "http://www.ncbi.nlm.nih.gov/pubmed/23777838", "http://www.ncbi.nlm.nih.gov/pubmed/14581621", "http://www.ncbi.nlm.nih.gov/pubmed/10080697", "http://www.ncbi.nlm.nih.gov/pubmed/22278767", "http://www.ncbi.nlm.nih.gov/pubmed/24249610", "http://www.ncbi.nlm.nih.gov/pubmed/20012672", "http://www.ncbi.nlm.nih.gov/pubmed/22573443", "http://www.ncbi.nlm.nih.gov/pubmed/12447549", "http://www.ncbi.nlm.nih.gov/pubmed/1467651", "http://www.ncbi.nlm.nih.gov/pubmed/20616380", "http://www.ncbi.nlm.nih.gov/pubmed/16228577", "http://www.ncbi.nlm.nih.gov/pubmed/16229815", "http://www.ncbi.nlm.nih.gov/pubmed/13376637", "http://www.ncbi.nlm.nih.gov/pubmed/19222806", "http://www.ncbi.nlm.nih.gov/pubmed/16663945" ], "ideal_answer": [ "Prolamellar body (PLB) is a highly organized lipid structure, which is the main site of accumulation of the ternary light-harvesting POR complex LHPP (light-harvesting NADPH:protochlorophyllide oxidoreductase:protochlorophyllide). Prolamellar bodies have been discovered in etioplasts with the use of thin section electron microscopy. Etioplasts develop in the place of chloroplasts in the dark. During skotomorphogenesis in angiosperms, NADPH:protochlorophyllide oxidoreductase (POR) forms the photolabile NADPH-POR-protochlorophyllide (Pchlide) ternary complexes. Prolamellar bodies (PLBs) efficiently capture the light energy for photo conversion in etioplasts. Upon illumination, the etioplasts transformed into regular chloroplasts. PLBs are formed not only in etioplasts but also in chloroplasts in young developing leaves during the night." ], "exact_answer": [ [ "etioplasts (mainly)" ], [ "chloroplasts (in young developing leaves during the night)" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043226", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009541" ], "type": "list", "id": "5543a1b2ee40ea110c000001", "snippets": [ { "offsetInBeginSection": 881, "offsetInEndSection": 1097, "text": "CPP1 depletion also causes reduced POR accumulation in etioplasts of dark-grown plants and as a result impairs the formation of prolamellar bodies, which subsequently affects chloroplast biogenesis upon illumination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24151298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Prolamellar bodies (PLBs) isolated from etiolated wheat seedlings were studied with the use of atomic force microscopy (AFM), transmission electron microscopy (TEM) and fluorescence spectroscopy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777838", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 421, "text": "TEM analyses confirmed that PLBs of wheat leaf etioplasts also had an average diameter of appr. 1\u03bcm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777838", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 796, "text": "etioplasts with prolamellar bodies (PLBs) and photoactive, 655nm emitting Pchlide form accumulated primarily in the basal leaf regions after 2 weeks of regeneration. When these latter leaves were illuminated with continuous light for 3 days, the etioplasts transformed into regular chloroplasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23415648", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1100, "text": "POR complex assembly (including LHPP and POR dimers) did not affect the formation of prolamellar bodies (PLBs) that function for efficient capture of light energy for photo conversion in etioplasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704664", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 674, "text": "Etioplasts that develop in the place of chloroplasts in the dark contain a highly organized lipid structure termed prolamellar body (PLB), which is the main site of accumulation of the ternary Pchlide:POR:NADPH complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22573443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "During skotomorphogenesis in angiosperms, NADPH:protochlorophyllide oxidoreductase (POR) forms an aggregate of photolabile NADPH-POR-protochlorophyllide (Pchlide) ternary complexes localized to the prolamellar bodies within etioplasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22278767", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 944, "text": "The content of the supramolecular light-harvesting POR complex LHPP (light-harvesting NADPH:protochlorophyllide oxidoreductase:protochlorophyllide) and the density of prolamellar bodies in etioplasts are decreased in the mutant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616380", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 734, "text": "The Arabidopsis porB-1 porC-1 mutant displays a severe xantha (highly chlorophyll-deficient) phenotype characterized by smaller prolamellar bodies in etioplasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20012672", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 644, "text": "The most notable contributions of thin section electron microscopy include the elucidation of the 3-D organization of thylakoid membranes, the discovery of prolamellar bodies in etioplasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16228577", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 809, "text": "This resulted in the recovery of thylakoid membrane stacking in chloroplasts in the light, and the formation of prolamellar bodies and plastoglobuli in etioplasts in the dark.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12447549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The prolamellar body (PLB) proteome of dark-grown wheat leaves was characterized. PLBs are formed not only in etioplasts but also in chloroplasts in young developing leaves during the night", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18071923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "A fraction of highly purified prolamellar bodies was isolated from etioplasts of wheat (Triticum aestivum L.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24249610", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 588, "text": "The highest specific activity of the enzyme in etiolated leaf tissue was confirmed to be in the fraction of prolamellar bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24249610", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1311, "text": "This work reveals a new view on the formation of prolamellar bodies and provides new clues about the function of POR in the etioplast-chloroplast transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19222806", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 780, "text": "The Arabidopsis porB-1 porC-1 mutant displays a severe xantha (highly chlorophyll-deficient) phenotype characterized by smaller prolamellar bodies in etioplasts and decreased thylakoid stacking in chloroplasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20012672", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 810, "text": "Transmission electron microscopy revealed partially developed, agranal plastids in the dark-grown mutant, unlike wild-type seedlings that contain etioplasts with prolamellar bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1467651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Organization of protochlorophyllide oxidoreductase in prolamellar bodies isolated from etiolated carotenoid-deficient wheat leaves as revealed by fluorescence probes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16229815", "endSection": "title" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1062, "text": "In fully etiolated leaves lamellae are absent and the prolamellar bodies become quite large, presumably because of inhibition of the fusion step which appears to require chlorophyll.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/13376637", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 397, "text": "POR is a peripheral membrane protein that accumulates to high levels in the prolamellar bodies of vascular plant etioplasts and is present at low levels in the thylakoid membranes of developing and mature plastids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10080697", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1320, "text": "This work reveals a new view on the formation of prolamellar bodies and provides new clues about the function of POR in the etioplast-chloroplast transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19222806", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1300, "text": "The results presented in this paper are not consistent with the hypothesis that the molar ratio of MGDG/DGDG is responsible for the tubular structure of prolamellar bodies in etioplasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24232321", "endSection": "abstract" } ] }, { "body": "What do mepolizumab and reslizumab have in common?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "http://www.ncbi.nlm.nih.gov/pubmed/21824072", "http://www.ncbi.nlm.nih.gov/pubmed/26285457", "http://www.ncbi.nlm.nih.gov/pubmed/23742015", "http://www.ncbi.nlm.nih.gov/pubmed/22092535", "http://www.ncbi.nlm.nih.gov/pubmed/25671117", "http://www.ncbi.nlm.nih.gov/pubmed/24275927", "http://www.ncbi.nlm.nih.gov/pubmed/20565230", "http://www.ncbi.nlm.nih.gov/pubmed/19037962" ], "ideal_answer": [ "Mepolizumab and reslizumab are monoclonal antibodies that target and neutralize interleukin 5. They have been shown to reduce eosinophil counts and they are used for the treatment of refractory asthma (associated with eosiniphilia) and other eosinophilic diseases." ], "exact_answer": [ [ "monoclonal antibodies" ], [ "treatment for refractory asthma" ], [ "treatment for eosinophilic disease" ], [ "neutralize interleukin 5" ], [ "reduce eosinophil counts" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4002251", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015848" ], "type": "list", "id": "56cf2be73975bb303a000005", "snippets": [ { "offsetInBeginSection": 992, "offsetInEndSection": 1224, "text": "The most promising agents are targeted against cytokines of Th2 pattern and related receptors, such as IL-2 (daclizumab) and IL-13 (lebrikizumab) or IL-5 in patients with hypereosinophilia (mepolizumab, reslizumab and benralizumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25671117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Patients with severe asthma or COPD have often a suboptimal symptom control due to inadequate treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25671117", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 1214, "text": "For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor \u03b1-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742015", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 751, "text": "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1634, "text": "In patients with severe, refractory asthma associated with eosinophilia, however, clinical trials have demonstrated significant reductions in asthma exacerbations. Clinical studies in other disorders, particularly eosinophilic esophagitis and hypereosinophilic syndrome, have also shown significant improvements in blood and/or tissue eosinophilia and variable alterations in clinical disease activity. Strategies aimed at the inhibition of IL-5 may hold great promise in the treatment of eosinophilic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1145, "text": "Two monoclonal antibodies have been designed to neutralize IL-5 (mepolizumab and reslizumab). Both antibodies have demonstrated the ability to reduce blood and tissue eosinophil counts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22092535", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1141, "text": "Two monoclonal antibodies have been designed to neutralize IL-5 (mepolizumab and reslizumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22092535", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 817, "text": "To date, two humanized monoclonal antibodies, mepolizumab and reslizumab, have been developed that bind to human IL-5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21824072", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 439, "text": "Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26285457", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 986, "text": "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1449, "text": "The most promising agents are targeted against cytokines of Th2 pattern and related receptors, such as IL-2 (daclizumab) and IL-13 (lebrikizumab) or IL-5 in patients with hypereosinophilia (mepolizumab, reslizumab and benralizumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25671117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26285457", "endSection": "abstract" } ] }, { "body": "When are itaconic acid levels elevated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23610393", "http://www.ncbi.nlm.nih.gov/pubmed/25209111", "http://www.ncbi.nlm.nih.gov/pubmed/25064235" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/id/C0951348" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7819222", "o": "itaconic acid, copper salt" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/label/A0196938" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0196938", "o": "itaconic 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"http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O49144", "o": "http://linkedlifedata.com/resource/#_4F343931343400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F34393134340010", "o": "http://linkedlifedata.com/resource/#_4F343931343400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F343931343400F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F353030333700F", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O50037", "o": "http://linkedlifedata.com/resource/#_4F353030333700F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F35303033370010", "o": "http://linkedlifedata.com/resource/#_4F353030333700F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F353030333700F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3634393936005", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O64996", "o": "http://linkedlifedata.com/resource/#_4F3634393936005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F3634393936006", "o": "http://linkedlifedata.com/resource/#_4F3634393936005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F3634393936005", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513057534338006", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q0WSC8", "o": "http://linkedlifedata.com/resource/#_513057534338006" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_513057534338007", "o": "http://linkedlifedata.com/resource/#_513057534338006" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513057534338006", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/chromomethylase", "o": "chromomethylase" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3634393934005", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O64994", "o": "http://linkedlifedata.com/resource/#_4F3634393934005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F3634393934006", "o": "http://linkedlifedata.com/resource/#_4F3634393934005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F3634393934005", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42365A43513700D", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B6ZCQ7", "o": "http://linkedlifedata.com/resource/#_42365A43513700D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42365A43513700E", "o": "http://linkedlifedata.com/resource/#_42365A43513700D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42365A43513700D", "o": "http://purl.uniprot.org/core/Structured_Name" } ], "ideal_answer": [ "No. Multiple lines of experimental evidence suggest that chromomethylases (CMTs) have been hitherto identified in plant genomes(Arabidopsis, maize, tomato). CMTs maintain CpNpG (N = A, T, C, or G) methylation and they are unique to the plant kingdom. The lack of CMT homologs in animal genomes could be explained based on the fact that, in contrast to plants, animals maintain primarily CG methylation. Therefore, the presence of CMTs is not required in the animal genomes." ], "exact_answer": "no", "concepts": [ "http://www.uniprot.org/uniprot/CMT3_ARATH", "http://www.uniprot.org/uniprot/CMT2_ARATH", "http://www.uniprot.org/uniprot/CMT1_ARATH" ], "type": "yesno", "id": "5171833c8ed59a060a00000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Many plant, animal, and fungal genomes contain cytosine DNA methylation in asymmetric sequence contexts (CpHpH, H = A, T, C).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12151602", "endSection": "sections.0" }, { "offsetInBeginSection": 852, "offsetInEndSection": 996, "text": "However, at the SUPERMAN locus, asymmetric methylation was only completely abolished in drm1 drm2 chromomethylase 3 (cmt3) triple mutant plants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12151602", "endSection": "sections.0" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1486, "text": "Although neither the drm1 drm2 double mutants nor the cmt3 single mutants show morphological defects, drm1 drm2 cmt3 triple mutant plants show pleiotropic effects on plant development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12151602", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "endSection": "title" }, { "offsetInBeginSection": 558, "offsetInEndSection": 705, "text": "The lack of CMT homologs in animal genomes could account for the observation that in contrast to plants, animals maintain primarily CG methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23021223", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "A role for CHROMOMETHYLASE3 in mediating transposon and euchromatin silencing during egg cell reprogramming in Arabidopsis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "During embryogenesis there is a major switch from dependence upon maternally-deposited products to reliance on products of the zygotic genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "endSection": "sections.0" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1556, "text": "Expression analysis of eight putative tomato DNA methyltransferases encoding genes showed that one chromomethylase (CMT) and two rearranged methyltransferases (DRMs) are preferentially expressed in the pericarp during fruit growth and could be involved in the locus-specific increase of methylation observed at this developmental phase in the pericarp.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18488247", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Natural variation for alleles under epigenetic control by the maize chromomethylase zmet2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17660570", "endSection": "title" }, { "offsetInBeginSection": 233, "offsetInEndSection": 516, "text": "Arabidopsis has two types of methyltransferases with demonstrated maintenance activity: MET1, which maintains CpG methylation and is homologous to mammalian DNMT1, and CHROMOMETHYLASE 3 (CMT3), which maintains CpNpG (N = A, T, C, or G) methylation and is unique to the plant kingdom.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12121623", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Maize chromomethylase Zea methyltransferase2 is required for CpNpG methylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "A cytosine DNA methyltransferase containing a chromodomain, Zea methyltransferase2 (Zmet2), was cloned from maize. The sequence of ZMET2 is similar to that of the Arabidopsis chromomethylases CMT1 and CMT3, with C-terminal motifs characteristic of eukaryotic and prokaryotic DNA methyltransferases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "endSection": "sections.0" }, { "offsetInBeginSection": 96, "offsetInEndSection": 427, "text": "We have detected a chromodomain embedded within the catalytic region of a predicted Arabidopsis DNA methyltransferase that is diverged from other eukaryotic enzymes. The 791 residue \"chromomethylase\" (CMT1) is encoded by a floral transcript that is spliced from 20 exons and is present at only approximately 1/10(-7) of total mRNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9584105", "endSection": "sections.0" } ] }, { "body": "Which genes are associated with autosomal dominant Charcot-Marie-Tooth?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25337607", "http://www.ncbi.nlm.nih.gov/pubmed/14561495", "http://www.ncbi.nlm.nih.gov/pubmed/12707075", "http://www.ncbi.nlm.nih.gov/pubmed/16775366", "http://www.ncbi.nlm.nih.gov/pubmed/24894446", "http://www.ncbi.nlm.nih.gov/pubmed/15099592", "http://www.ncbi.nlm.nih.gov/pubmed/12481988", "http://www.ncbi.nlm.nih.gov/pubmed/18492089", "http://www.ncbi.nlm.nih.gov/pubmed/17636067", "http://www.ncbi.nlm.nih.gov/pubmed/22451505", "http://www.ncbi.nlm.nih.gov/pubmed/22096584", "http://www.ncbi.nlm.nih.gov/pubmed/12566280", "http://www.ncbi.nlm.nih.gov/pubmed/25326399", "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "http://www.ncbi.nlm.nih.gov/pubmed/18975529", "http://www.ncbi.nlm.nih.gov/pubmed/12525712", "http://www.ncbi.nlm.nih.gov/pubmed/8655146", "http://www.ncbi.nlm.nih.gov/pubmed/22091729", "http://www.ncbi.nlm.nih.gov/pubmed/17052987", "http://www.ncbi.nlm.nih.gov/pubmed/19502294", "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "http://www.ncbi.nlm.nih.gov/pubmed/22781092", "http://www.ncbi.nlm.nih.gov/pubmed/21753178", "http://www.ncbi.nlm.nih.gov/pubmed/15731758" ], "ideal_answer": [ "The genes associated with the X-linked and the autosomal dominant forms of Charcot-Marie-Tooth disease are GJB1, MPZ, INF2, DNM2, YARS, GNB4, NEFL, MFN2, LRSAM1, GDAP1, PMP22, LITAF, and EGR2. Identification of these genes has not only been important for patients and families, but also provided new information about disease pathogenesis." ], "exact_answer": [ [ "GJB1" ], [ "MPZ" ], [ "INF2" ], [ "DNM2" ], [ "YARS" ], [ "GNB4" ], [ "NEFL" ], [ "MFN2" ], [ "LRSAM1" ], [ "GDAP1" ], [ "PMP22" ], [ "LITAF" ], [ "EGR2" ] ], "type": "list", "id": "5713bc991174fb1755000010", "snippets": [ { "offsetInBeginSection": 505, "offsetInEndSection": 853, "text": " GJB1 is currently considered to be associated with X-linked DI-CMT, and MPZ, INF2, DNM2, YARS, GNB4, NEFL, and MFN2 are associated with autosomal DI-CMT. Moreover, GDAP1, KARS, and PLEKHG5 are associated with RI-CMT. Identification of these genes is not only important for patients and families but also provides new information about pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant inheritance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894446", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 642, "text": "Charcot-Marie-Tooth disease (CMT) refers to a heterogeneous group of genetic motor and sensory neuropathies. According to the primary site of damage, a distinction is made between demyelinating and axonal forms (CMT1 and 2, respectively, when inherited as an autosomal dominant trait). Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) is a ubiquitin-protein ligase with a role in sorting internalised cell-surface receptor proteins. So far, mutations in the LRSAM1 gene have been shown to cause axonal CMT in three different families and can confer either dominant or recessive transmission of the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894446", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 750, "text": "We have identified a novel mutation in LRSAM1 in a small family with dominant axonal CMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Mutations in the ganglioside-induced-differentiation-associated protein 1 gene (GDAP1) can cause Charcot-Marie-Tooth (CMT) disease with demyelinating (CMT4A) or axonal forms (CMT2K and ARCMT2K). Most of these mutations present a recessive inheritance, but few autosomal dominant GDAP1 mutations have also been reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1460, "text": " Our findings highlight the relevance of dominantly transmitted p.R120W GDAP1 gene mutations which can cause an axonal CMT with a wide clinical profile", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "endSection": "title" }, { "offsetInBeginSection": 279, "offsetInEndSection": 361, "text": "There have been very few reports of GDAP1 mutations in autosomal dominant (AD) CMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 441, "text": "Here, we report an AD CMT family with a novel Q218E mutation in the GDAP1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 948, "text": "CMT type 1 (CMT1; MIM 118200) is a group of autosomal dominant-inherited demyelinating neuropathies with a disease onset at or after childhood. Five different subtypes have been identified based on different causative genes. Among them, CMT1A (MIM #118220) is most common and is usually associated with a duplication of a 1.5-Mb region on chromosome 17p11.2, which includes peripheral myelin protein 22 gene (PMP22; MIM *601097)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18975529", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 358, "text": "Mutations in the NF-L gene (NEFL) cause autosomal dominant neuropathies that are classified either as axonal Charcot-Marie-Tooth (CMT) type 2E (CMT2E) or demyelinating CMT type 1F (CMT1F)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17052987", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 249, "text": "Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17636067", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1203, "text": "Four genes (PMP22, MPZ, LITAF, and EGR2) have been described in the last 15 yr associated with AD CMTI and a further gene (NEFL), originally described as causing AD CMT2 can also cause AD CMT1 (by neurophysiological criteria)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16775366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15731758", "endSection": "title" }, { "offsetInBeginSection": 248, "offsetInEndSection": 519, "text": "We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 to 4.2 Mb in three unrelated families with CMT originating from Australia, Belgium and North America. After screening candidate genes, we identified unique mutations in dynamin 2 (DNM2) in all families", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15731758", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 442, "text": "Here, we report a large family showing characteristic phenotypes of Charcot-Marie-Tooth type 1A along with deafness in an autosomal dominant fashion. We detected a sequence variation (c.68C>G) co-segregating with the disease phenotype and leading to a T23R missense mutation in PMP22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15099592", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 249, "text": "The authors recently mapped an autosomal dominant demyelinating form of CMT type 1 (CMT1C) to chromosome 16p13.1-p12.3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525712", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 900, "text": "The authors identified missense mutations (G112S, T115N, W116G) in the LITAFgene (lipopolysaccharide-induced tumor necrosis factor-alpha factor) in three CMT1C pedigrees", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525712", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 846, "text": "We identified a novel neurofilament-light missense mutation (C64T) that causes the disease in a large Slovenian CMT2 family. This novel mutation shows complete co-segregation with the dominantly inherited CMT2 phenotype in our family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12481988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21753178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "endSection": "title" }, { "offsetInBeginSection": 529, "offsetInEndSection": 871, "text": "In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Mutations in dynamin 2 (DNM2) lead to dominant intermediate Charcot-Marie-Tooth neuropathy type B, while a different set of DNM2 mutations cause autosomal dominant centronuclear myopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot-Marie-Tooth disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22781092", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17636067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Mutations in the Dynamin 2 gene (DNM2) cause autosomal dominant centronuclear myopathy or autosomal dominant (AD) Charcot-Marie-Tooth (CMT) disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22091729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Mutations in the ganglioside-induced differentiation-associated protein 1 gene cause either autosomal recessive demyelinating Charcot-Marie-Tooth disease type 4A or autosomal recessive axonal Charcot-Marie-Tooth disease with vocal cord paresis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14561495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "A novel mutation in the GDAP1 gene is associated with autosomal recessive Charcot-Marie-Tooth disease in an Amish family", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18492089", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12707075", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin gene PMP22. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8655146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "OBJECTIVE: Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21753178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Mutations in the ganglioside-induced-differentiation-associated protein 1 gene (GDAP1) can cause Charcot-Marie-Tooth (CMT) disease with demyelinating (CMT4A) or axonal forms (CMT2K and ARCMT2K). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 259, "text": "Mutations in the NEFL gene were recently reported as a cause for autosomal dominant Charcot-Marie-Tooth type 2E (CMT2E) linked to chromosome 8p21. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12566280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and Charcot-Marie Tooth peripheral neuropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22096584", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21753178", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 816, "text": "In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy. We used tissue derived from Dnm2-deficient mice to establish an appropriate peripheral nerve model and found that dominant intermediate Charcot-Marie-Tooth neuropathy type B-associated dynamin 2 mutants, but not autosomal dominant centronuclear myopathy mutants, impaired myelination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 531, "text": " Mutations in dynamin 2 (DNM2) lead to dominant intermediate Charcot-Marie-Tooth neuropathy type B, while a different set of DNM2 mutations cause autosomal dominant centronuclear myopathy. In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451505", "endSection": "abstract" }, { "offsetInBeginSection": 1981, "offsetInEndSection": 2310, "text": "We conclude that dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype, especially when Charcot-Marie-Tooth is associated with neutropaenia or cataracts. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19502294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot-Marie-Tooth disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22781092", "endSection": "title" }, { "offsetInBeginSection": 1981, "offsetInEndSection": 2307, "text": "We conclude that dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype, especially when Charcot-Marie-Tooth is associated with neutropaenia or cataracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19502294", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 531, "text": "In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Mutations in the ganglioside-induced-differentiation-associated protein 1 gene (GDAP1) can cause Charcot-Marie-Tooth (CMT) disease with demyelinating (CMT4A) or axonal forms (CMT2K and ARCMT2K).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "A wide range of phenotypes have been reported in autosomal recessive (AR) Charcot-Marie-Tooth disease (CMT) patients carrying mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene, such as axonal, demyelinating, and intermediate forms of AR CMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25337607", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot-Marie-Tooth disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22781092", "endSection": "title" } ] }, { "body": "Which transcription factors (TFs) participate in the formation of the interferon-beta (IFN-b) enhanceosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10747925", "http://www.ncbi.nlm.nih.gov/pubmed/19944700", "http://www.ncbi.nlm.nih.gov/pubmed/15510218", "http://www.ncbi.nlm.nih.gov/pubmed/9659924", "http://www.ncbi.nlm.nih.gov/pubmed/9770462", "http://www.ncbi.nlm.nih.gov/pubmed/8548797", "http://www.ncbi.nlm.nih.gov/pubmed/9659909", "http://www.ncbi.nlm.nih.gov/pubmed/9809067", "http://www.ncbi.nlm.nih.gov/pubmed/10024886", "http://www.ncbi.nlm.nih.gov/pubmed/10848607", "http://www.ncbi.nlm.nih.gov/pubmed/18420790", "http://www.ncbi.nlm.nih.gov/pubmed/10357819" ], "ideal_answer": [ "Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y). Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. ", "Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B. However, HMG I(Y) plays an essential role in the assembly and function of the IFN beta gene enhanceosome." ], "exact_answer": [ [ "NF-kappa B (p50/p65)" ], [ "ATF-2" ], [ "c-jun" ], [ "IRF-3" ], [ "IRF-7" ], [ "IRF-1" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016899", "http://www.uniprot.org/uniprot/IFN_ANAPL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034206", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157", "http://www.biosemantics.org/jochem#4250284" ], "type": "list", "id": "54fb4b34d176fff445000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The dimer formed by the ATF-2 and c-Jun transcription factors is one of the main components of the human interferon-beta enhanceosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19944700", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 614, "text": "The induction of IFN transcription resulted from the activation of the components of the IFN-beta enhanceosome, i.e. IFN regulatory factor (IRF) 3, nuclear factor (NF)-kappaB, activating transcription factor (ATF)-2 and c-Jun.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18420790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF-3/IRF-7, NF-kappaB and HMGI(Y). These factors cooperatively bind a composite DNA site and activate expression of the IFN-beta gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15510218", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 457, "text": "Here we report that within the IFN-beta enhanceosome the ATF-2-c-jun heterodimer binds in a specific orientation, which is required for assembly of a complex between ATF-2-c-jun and interferon regulatory factor 3 (IRF-3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10848607", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 332, "text": " Here, we identified a small molecule that induces the assembly of the interferon-beta (IFN-beta) enhanceosome by stimulating all the enhancer-binding activator proteins: ATF2/c-JUN, IRF3, and p50/p65 of NF-kappaB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10747925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Transcriptional activation of the virus inducible enhancer of the human interferon-beta (IFN-beta) gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappaB, ATF-2/c-Jun, IRFs and the architectural protein of the mammalian high mobility group I(Y) [HMG I(Y)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10357819", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 818, "text": "Here, we demonstrate that the first step in enhanceosome assembly, i.e. HMG I(Y)-dependent recruitment of NF-kappaB and ATF-2/c-Jun to the enhancer, is facilitated by discrete regions of HMG I and is mediated by allosteric changes induced in the DNA by HMG I(Y) and not by protein-protein interactions between HMG I(Y) and these proteins. However, we show that completion of the enhanceosome assembly process requires protein-protein interactions between HMG I(Y) and the activators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10357819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10024886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "The transcriptional coactivators CBP and P/CAF are required for activation of transcription from the IFN beta enhanceosome. We show that CBP and P/CAF acetylate HMG I(Y), the essential architectural component required for enhanceosome assembly, at distinct lysine residues, causing distinct effects on transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9809067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "The transcriptional activity of an in vitro assembled human interferon-beta gene enhanceosome is highly synergistic. This synergy requires five distinct transcriptional activator proteins (ATF2/c-JUN, interferon regulatory factor 1, and p50/p65 of NF-kappaB), the high mobility group protein HMG I(Y), and the correct alignment of protein-binding sites on the face of the DNA double helix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9770462", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1042, "text": "In addition, we provide evidence that recruitment of the holoenzyme by the enhanceosome is due, at least in part, to interactions between the enhanceosome and the transcriptional coactivator CREB, cAMP responsive element binding protein (CBP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9770462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9659924", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 785, "text": "Transcriptional synergy requires recruitment of the CBP/p300 coactivator to the enhanceosome, via a new activating surface assembled from the novel p65 domain and the activation domains of all of the activators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9659924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 411, "text": "A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B. Maximal levels of transcriptional synergy between these activators required the specific interactions with the architectural protein HMG I(Y) and the correct helical phasing of the binding sites of these proteins on the DNA helix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9659909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "We present evidence that transcriptional activation of the human interferon-beta (IFN beta) gene requires the assembly of a higher order transcription enhancer complex (enhanceosome). This multicomponent complex includes at least three distinct transcription factors and the high mobility group protein HMG I(Y).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8548797", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 813, "text": "Thus, HMG I(Y) plays an essential role in the assembly and function of the IFN beta gene enhanceosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8548797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF-3/IRF-7, NF-kappaB and HMGI(Y).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15510218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9659909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10024886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9659924", "endSection": "abstract" } ] }, { "body": "Is low T3 syndrome related with high BNP in cardiac patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14678288", "http://www.ncbi.nlm.nih.gov/pubmed/20888651", "http://www.ncbi.nlm.nih.gov/pubmed/17375888", "http://www.ncbi.nlm.nih.gov/pubmed/16649727", "http://www.ncbi.nlm.nih.gov/pubmed/18620103", "http://www.ncbi.nlm.nih.gov/pubmed/18729306", "http://www.ncbi.nlm.nih.gov/pubmed/17646607", "http://www.ncbi.nlm.nih.gov/pubmed/18949097", "http://www.ncbi.nlm.nih.gov/pubmed/22870736", "http://www.ncbi.nlm.nih.gov/pubmed/8345811", "http://www.ncbi.nlm.nih.gov/pubmed/20492497", "http://www.ncbi.nlm.nih.gov/pubmed/12655635", "http://www.ncbi.nlm.nih.gov/pubmed/19423177", "http://www.ncbi.nlm.nih.gov/pubmed/12578873", "http://www.ncbi.nlm.nih.gov/pubmed/19181292", "http://www.ncbi.nlm.nih.gov/pubmed/17635576", "http://www.ncbi.nlm.nih.gov/pubmed/18073483", "http://www.ncbi.nlm.nih.gov/pubmed/16952785", "http://www.ncbi.nlm.nih.gov/pubmed/19221174", "http://www.ncbi.nlm.nih.gov/pubmed/19778808" ], "ideal_answer": [ "BNP and fT3 are independently associated in severely compromised HF patients.\nNT-pro-BNP was significantly associated with low-T3 syndrome in cardiac patients.\nHigher NT-pro BNP concentrations are related to lower total T3 concentrations in cardiac patients" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/ANFB_OREMO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005067", "http://www.disease-ontology.org/api/metadata/DOID:2856", "http://www.disease-ontology.org/api/metadata/DOID:1287", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020097" ], "type": "yesno", "id": "5321bb019b2d7acc7e00000b", "snippets": [ { "offsetInBeginSection": 1300, "offsetInEndSection": 1400, "text": "BNP and fT3 are independently associated with exercise capacity in severely compromised HF patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20888651", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 896, "text": "fter adjustment for known confounders, NT-pro-BNP was significantly associated with fT3 and low-T3 syndrome. fT3 (HR 0.58, 95%CI 0.34-0.98) and low-T3 syndrome (HR 3.0, 95%CI 1.4-6.3) were predictive for mortality after adjustment for NT-pro-BNP levels and other cardiovascular prognostic variables.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19423177", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1381, "text": "fT3 and low-T3 syndrome are significantly related to NT-pro-BNP in patients with cardiovascular disease, but are predictors of mortality independently of NT-pro-BNP and other known cardiovascular risk parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19423177", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1183, "text": "Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16649727", "endSection": "abstract" } ] }, { "body": "List packages for transcription factor binding sites' (TFBS) analysis available in R/Bioconductor", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23144600", "http://www.ncbi.nlm.nih.gov/pubmed/17402923", "http://www.ncbi.nlm.nih.gov/pubmed/17550915", "http://www.ncbi.nlm.nih.gov/pubmed/24267901", "http://www.ncbi.nlm.nih.gov/pubmed/12176838" ], "ideal_answer": [ "Neighbourhood Consistent PC (NCPC) algorithms, MMDiff and cosmo." ], "exact_answer": [ [ "Neighbourhood Consistent PC (NCPC) algorithms" ], [ "MMDiff" ], [ "cosmo" ], [ "dPattern" ], [ "TFBS" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0008134", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001665" ], "type": "list", "id": "56a39a32496b62f23f000005", "snippets": [ { "offsetInBeginSection": 230, "offsetInEndSection": 1589, "text": "Clustered occurrence of multiple TFs at genomic sites may arise from chromatin accessibility and local cooperation between TFs, or binding sites may simply appear clustered if the profiles are generated from diverse cell populations. Overlaps in TF binding profiles may also result from measurements taken at closely related time intervals. It is thus of great interest to distinguish TFs that directly regulate gene expression from those that are indirectly associated with gene expression. Graphical models, in particular Bayesian networks, provide a powerful mathematical framework to infer different types of dependencies. However, existing methods do not perform well when the features (here: TF binding profiles) are highly correlated, when their association with the biological outcome is weak, and when the sample size is small. Here, we develop a novel computational method, the Neighbourhood Consistent PC (NCPC) algorithms, which deal with these scenarios much more effectively than existing methods do. We further present a novel graphical representation, the Direct Dependence Graph (DDGraph), to better display the complex interactions among variables. NCPC and DDGraph can also be applied to other problems involving highly correlated biological features. Both methods are implemented in the R package ddgraph, available as part of Bioconductor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144600", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 817, "text": "Here, we present MMDiff, a robust, broadly applicable method for detecting differences between sequence count data sets. Based on quantifying shape changes in signal profiles, it overcomes challenges imposed by the highly structured nature of the data and the paucity of replicates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24267901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Supervised detection of conserved motifs in DNA sequences with cosmo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17402923", "endSection": "title" }, { "offsetInBeginSection": 187, "offsetInEndSection": 716, "text": "We here introduce an algorithm, called cosmo, that allows this search to be supervised by specifying a set of constraints that the position weight matrix of the unknown motif must satisfy. Such constraints may be formulated, for example, on the basis of prior knowledge about the structure of the transcription factor in question. The algorithm is based on the same two-component multinomial mixture model used by MEME, with stronger reliance, however, on the likelihood principle instead of more ad-hoc criteria like the E-value", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17402923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "dPattern: transcription factor binding site (TFBS) discovery in human genome using a discriminative pattern analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17550915", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "TFBS: Computational framework for transcription factor binding site analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12176838", "endSection": "title" } ] }, { "body": "Simpson grading is used to describe resection of which brain tumor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12605979", "http://www.ncbi.nlm.nih.gov/pubmed/25774702", "http://www.ncbi.nlm.nih.gov/pubmed/24965072", "http://www.ncbi.nlm.nih.gov/pubmed/25464274", "http://www.ncbi.nlm.nih.gov/pubmed/22839654", "http://www.ncbi.nlm.nih.gov/pubmed/20380529", "http://www.ncbi.nlm.nih.gov/pubmed/23061394", "http://www.ncbi.nlm.nih.gov/pubmed/24053497", "http://www.ncbi.nlm.nih.gov/pubmed/24193889" ], "ideal_answer": [ "The Simpson grading system was used to assess the extent of surgical resection of meningioma." ], "exact_answer": [ "meningioma" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932" ], "type": "factoid", "id": "56c1f010ef6e394741000041", "snippets": [ { "offsetInBeginSection": 558, "offsetInEndSection": 1283, "text": "The impact of age (\u2264 70 vs.>70 years), sex, tumor diameter (<6 vs. \u2265 6 cm), pre- and postoperative KPS (<80 vs. \u2265 80), Simpson grade (I-II vs. III-IV), and World Health Organization (WHO) histologic grade (I vs. II-III) on survival was assessed. Kaplan-Meier survival curves were plotted and differences in survival between groups of patients were compared. A multivariate analysis adjusted for age, pre- and postoperative KPS, Simpson grade, tumor diameter, and WHO histologic grade also was performed.RESULTS: The fronto-orbito-basal approach (n = 22) allowed a significantly greater percentage of Simpson I-II removals than the bifrontal (n = 70) and pterional approach (n = 21) (P = 0.0354 and P = 0.0485, respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25464274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Simpson Grade I-III Resection of Spinal Atypical (World Health Organization Grade II) Meningiomas is Associated With Symptom Resolution and Low Recurrence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25774702", "endSection": "title" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1293, "text": "Simpson grade I, II, III, and IV resection were achieved in 3 (15%), 13 (65%), 2 (10%), and 2 (10%) tumors, respectively. One patient that underwent Simpson grade III resection received adjuvant radiation therapy. After Simpson grade I-III or gross total resection, no tumors recurred (0%; confidence interval, 0%-17.6%). After Simpson grade IV resection, 1 tumor recurred (50%; confidence interval, 1.3%-98.7%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25774702", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 923, "text": " The Simpson grading system was used to assess the extent of surgical resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24965072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Simpson grade: an opportunity to reassess the need for complete resection of meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24193889", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "BACKGROUND: The relevance of the Simpson grading system as a predictor of meningioma progression or recurrence in modern neurosurgical practice has recently been called into question. The aim of our study was to compare the risk of progression/recurrence of tumours that had been treated with different Simpson grade resections in a contemporary population of benign (WHO grade I) meningioma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24193889", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 1291, "text": "RESULTS: The three-year progression/recurrence-free survival rates for patients receiving Simpson grade 1, 2 or 4 resections were 95 %, 87 % and 67 %, respectively. Simpson grade 4 resections progressed/recurred at a significantly greater rate than Simpson grade 1 resections (hazard ratio [HR]\u2009=\u20093.26, P\u2009=\u20090.04), whereas Simpson grade 2 resections did not progress/recur at a significantly greater rate than Simpson grade 1 resections (HR\u2009=\u20091.78, P\u2009=\u20090.29).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24193889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson grade IV resection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24053497", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 931, "text": "The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection.METHODS: This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24053497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12605979", "endSection": "title" }, { "offsetInBeginSection": 1504, "offsetInEndSection": 2430, "text": "Multivariate analysis revealed that no dural detachment (hazard ratio [HR]6.42, 95% CI 1.41-45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18-218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm(3) or more was not a statistically significant risk factor.CONCLUSIONS: Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24053497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The relevance of Simpson Grade I and II resection in modern neurosurgical treatment of World Health Organization Grade I meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20380529", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Surgery for convexity meningioma: Simpson Grade I resection as the goal: clinical article.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23061394", "endSection": "title" }, { "offsetInBeginSection": 2931, "offsetInEndSection": 3084, "text": "However, for skull base meningiomas, in which mostly Simpson Grade II resection is achieved, the use of this classification should be further validated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22839654", "endSection": "abstract" } ] }, { "body": "Where in the cell do we find the protein Cep135?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20392737", "http://www.ncbi.nlm.nih.gov/pubmed/22898782", "http://www.ncbi.nlm.nih.gov/pubmed/16240430", "http://www.ncbi.nlm.nih.gov/pubmed/17681131", "http://www.ncbi.nlm.nih.gov/pubmed/18851962", "http://www.ncbi.nlm.nih.gov/pubmed/23213374", "http://www.ncbi.nlm.nih.gov/pubmed/19321663", "http://www.ncbi.nlm.nih.gov/pubmed/22976301", "http://www.ncbi.nlm.nih.gov/pubmed/21766470", "http://www.ncbi.nlm.nih.gov/pubmed/22261722", "http://www.ncbi.nlm.nih.gov/pubmed/23115304", "http://www.ncbi.nlm.nih.gov/pubmed/10842375", "http://www.ncbi.nlm.nih.gov/pubmed/19454482", "http://www.ncbi.nlm.nih.gov/pubmed/22521416", "http://www.ncbi.nlm.nih.gov/pubmed/14983524", "http://www.ncbi.nlm.nih.gov/pubmed/11781336", "http://www.ncbi.nlm.nih.gov/pubmed/19293139", "http://www.ncbi.nlm.nih.gov/pubmed/23456457" ], "ideal_answer": [ "centrosome" ], "exact_answer": [ "centrosome" ], "concepts": [ "http://www.uniprot.org/uniprot/CP135_HUMAN" ], "type": "factoid", "id": "51596a8ad24251bc0500009e", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 219, "text": "CEP family protein is the active component of centrosome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23456457", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Cep135/Bld10 is a conserved centriolar protein required for the formation of the central cartwheel, an early intermediate in centriole assembly.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22976301", "endSection": "sections.0" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1157, "text": "Thus, in flies, Cep135/Bld10 is not essential for cartwheel assembly or for establishing the ninefold symmetry of centrioles; rather, it appears to stabilize the connection between inner and outer centriole components.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22976301", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Cep135 is a 135-kDa, coiled-coil centrosome protein important for microtubule organization in mammalian cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14983524", "endSection": "sections.0" }, { "offsetInBeginSection": 634, "offsetInEndSection": 670, "text": "135\u00a0kDa centrosomal protein (CEP135)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22521416", "endSection": "sections.0" }, { "offsetInBeginSection": 301, "offsetInEndSection": 415, "text": "In the present study, we investigated a novel interaction between CEP135 and C-NAP1, two core centriolar proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18851962", "endSection": "sections.0" }, { "offsetInBeginSection": 350, "offsetInEndSection": 520, "text": "Drosophila Bld10, the ortholog of Chlamydomonas reinhardtii Bld10p and human Cep135, is a ubiquitous centriolar protein that also localizes to the spermatid basal body. M", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19321663", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BLD10/CEP135 is a microtubule-associated protein that controls the formation of the flagellum central microtubule pair.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22898782", "endSection": "title" }, { "offsetInBeginSection": 683, "offsetInEndSection": 877, "text": "We found an evolutionarily cohesive and ancestral module, which we term UNIMOD and is defined by three components (SAS6, SAS4/CPAP and BLD10/CEP135), that correlates with the occurrence of CBBs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20392737", "endSection": "sections.0" }, { "offsetInBeginSection": 717, "offsetInEndSection": 783, "text": "pericentriolar material proteins including pericentrin and CEP135.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261722", "endSection": "sections.0" }, { "offsetInBeginSection": 690, "offsetInEndSection": 802, "text": "hereas Cep135 and CPAP formed a core structure within the proximal lumen of both parental and nascent centrioles", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17681131", "endSection": "sections.0" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1016, "text": ". Centrosome components, including \u03b3-tubulin and Cep135,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21766470", "endSection": "sections.0" }, { "offsetInBeginSection": 257, "offsetInEndSection": 324, "text": "suggesting that Cep135 is a structural component of the centrosome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10842375", "endSection": "sections.0" } ] }, { "body": "Is delayed enhancement documented in patients with non-ischemic dilated cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17131077", "http://www.ncbi.nlm.nih.gov/pubmed/21176853", "http://www.ncbi.nlm.nih.gov/pubmed/22875171", "http://www.ncbi.nlm.nih.gov/pubmed/23021326", "http://www.ncbi.nlm.nih.gov/pubmed/17885521", "http://www.ncbi.nlm.nih.gov/pubmed/19185371", "http://www.ncbi.nlm.nih.gov/pubmed/19317068", "http://www.ncbi.nlm.nih.gov/pubmed/23422782", "http://www.ncbi.nlm.nih.gov/pubmed/20118568", "http://www.ncbi.nlm.nih.gov/pubmed/17602984", "http://www.ncbi.nlm.nih.gov/pubmed/22552168", "http://www.ncbi.nlm.nih.gov/pubmed/21234292", "http://www.ncbi.nlm.nih.gov/pubmed/20149594", "http://www.ncbi.nlm.nih.gov/pubmed/24315973" ], "ideal_answer": [ "Delayed enhancement is documented in almost 30% of patients with non-ischemic dilated cardiomyopathy and its pattern is characterized by mid-wall, patchy or diffuse location." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009682", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.disease-ontology.org/api/metadata/DOID:12930", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311" ], "type": "yesno", "id": "5339ed7bd6d3ac6a34000060", "snippets": [ { "offsetInBeginSection": 714, "offsetInEndSection": 814, "text": "Myocardial fibrosis was present in 30% of patients, the majority of which was mid-myocardial (63%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21234292", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1400, "text": " DCM patients frequently have myocardial fibrosis detected on CE-CMR, the majority of which is mid-myocardial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21234292", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 689, "text": "Fifty (40%) patients showed myocardial DE, representing 12\u00b17% of LV mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21176853", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 675, "text": "one case was dilated cardiomyopathy, in which the delayed enhancement was diffuse small midwall spots ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19317068", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1013, "text": "In the dilated cardiomyopathy group, only seven (29%) patients showed delayed enhancement and its pattern was characterized by mid-wall, patchy or diffuse location.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17885521", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1838, "text": "Patterns of delayed enhancement are different in dilated cardiomyopathy and ischemic cardiomyopathy, reflecting the presence of scarring or various degrees of fibrosis in left ventricular myocardium. The presence of subendocardial or transmural delayed enhancement at contrast-enhanced cardiovascular magnetic resonance allowed distinction between dilated cardiomyopathy and ischemic cardiomyopathy with high sensitivity (88%) and specificity (100%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17885521", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by Varespladib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23590147", "http://www.ncbi.nlm.nih.gov/pubmed/19697278", "http://www.ncbi.nlm.nih.gov/pubmed/24115030", "http://www.ncbi.nlm.nih.gov/pubmed/24247616", "http://www.ncbi.nlm.nih.gov/pubmed/23349189", "http://www.ncbi.nlm.nih.gov/pubmed/22281412", "http://www.ncbi.nlm.nih.gov/pubmed/21098449", "http://www.ncbi.nlm.nih.gov/pubmed/25533115", "http://www.ncbi.nlm.nih.gov/pubmed/24864079", "http://www.ncbi.nlm.nih.gov/pubmed/24419257", "http://www.ncbi.nlm.nih.gov/pubmed/21602519" ], "ideal_answer": [ "Varespladib is a secretory phospholipase A2 (sPLA2) inhibitor. It was tested in patients with acute coronary syndrome." ], "exact_answer": [ "secretory phospholipase A2" ], "concepts": [ "http://www.biosemantics.org/jochem#4240439", "http://www.biosemantics.org/jochem#4240440", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4240439", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798" ], "type": "factoid", "id": "56c1f00def6e39474100003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The VISTA-16 trial of varespladib, a secretory phospholipase A2 (sPLA2) inhibitor, in patients with an acute coronary syndrome was terminated prematurely owing to futility and a signal towards harm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24419257", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1269, "text": "Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24864079", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 367, "text": "The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown.OBJECTIVE: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247616", "endSection": "abstract" }, { "offsetInBeginSection": 2164, "offsetInEndSection": 2298, "text": "The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247616", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 728, "text": "The potential pro-atherogenic role of PLA(2) led to the development of two small molecules, varespladib, a reversible sPLA(2) inhibitor, and darapladib, a selective Lp-PLA(2) inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533115", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1667, "text": "In the present article, the enzymatic properties and the involvement of sPLA(2) and Lp-PLA(2) in atherogenesis are reviewed, with a focus on the results of experimental studies and clinical studies with both varespladib and darapladib inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "OBJECTIVE: Several secreted phospholipases A2 (sPLA2s), including group IIA, III, V, and X, have been linked to the development of atherosclerosis, which led to the clinical testing of A-002 (varespladib), a broad sPLA2 inhibitor for the treatment of coronary artery disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349189", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1142, "text": "Varespladib was able to inhibit sPLA2 in the types of neonatal lung injury investigated. sPLA2 activity was reduced in hyaline membrane disease (P < .0001), infections (P = .003), and meconium aspiration (P = .04) using 40 \u00b5M varespladib; 10 \u00b5M was able to lower enzyme activity (P = .001), with an IC(50) of 87 \u00b5M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21602519", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 483, "text": "Varespladib methyl is a prodrug that is rapidly metabolized to varespladib, and both compounds are able to potently inhibit the enzymes of the human secretory phospholipase groups IIa, V and X, which play a pivotal role in atherosclerotic disease and inflammation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19697278", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 1199, "text": "The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown.OBJECTIVE: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes.DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n\u2009=\u20092572) or placebo (n\u2009=\u20092573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012).INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies.MAIN OUTCOMES AND MEASURES: The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247616", "endSection": "abstract" }, { "offsetInBeginSection": 1771, "offsetInEndSection": 2361, "text": "The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P\u2009=\u2009.04).CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247616", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 661, "text": "The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA(2) would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention.METHODS AND RESULTS: Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098449", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 711, "text": "We evaluated whether endothelial function is attenuated after PCI and if inhibition of secretory phospholipase A2 (sPLA2) activity augments endothelial function and coronary flow reserve (CFR) in these patients.METHODS: In the sPLA2 Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) study, patients undergoing elective PCI were randomized to receive Varespladib (Anthera Pharmaceuticals Inc, San Mateo, CA), an inhibitor of sPLA2, or placebo 3-5 days prior to PCI and for 5 days after PCI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22281412", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 1011, "text": "The present study evaluated the effects of sPLA2-IIA inhibition with varespladib acid in a novel mouse model, human apolipoprotein B (apoB)/human cholesteryl ester transfer protein (CETP)/human sPLA2-IIA triple transgenic mice (TTT) fed a Western-type diet.APPROACH AND RESULTS: sPLA2-IIA expression increased atherosclerotic lesion formation in TTT compared with human apoB/human CETP double transgenic mice (P<0.01). Varespladib acid effectively inhibited plasma sPLA2-IIA activity. Surprisingly, however, administration of varespladib acid to TTT had no impact on atherosclerosis, which could be attributed to a proatherogenic plasma lipoprotein profile that appears in response to sPLA2-IIA inhibition because of increased plasma CETP activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24115030", "endSection": "abstract" }, { "offsetInBeginSection": 1729, "offsetInEndSection": 1845, "text": "Acute inhibition of sPLA2 activity with Varespladib does not affect endothelial or microvascular function after PCI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22281412", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 982, "text": "Varespladib acid effectively inhibited plasma sPLA2-IIA activity. Surprisingly, however, administration of varespladib acid to TTT had no impact on atherosclerosis, which could be attributed to a proatherogenic plasma lipoprotein profile that appears in response to sPLA2-IIA inhibition because of increased plasma CETP activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24115030", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 522, "text": "We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity. Alveolar macrophages were cultured and stimulated with lipopolysaccharide and then treated with either varespladib, surfactant, varespladib followed by surfactant or nothing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23590147", "endSection": "abstract" } ] }, { "body": "Which protein does empagliflozin inhibit?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "http://www.ncbi.nlm.nih.gov/pubmed/25488697", "http://www.ncbi.nlm.nih.gov/pubmed/23054692", "http://www.ncbi.nlm.nih.gov/pubmed/24622320", "http://www.ncbi.nlm.nih.gov/pubmed/25369239", "http://www.ncbi.nlm.nih.gov/pubmed/23906374", "http://www.ncbi.nlm.nih.gov/pubmed/25419452", "http://www.ncbi.nlm.nih.gov/pubmed/24226524", "http://www.ncbi.nlm.nih.gov/pubmed/24007456", "http://www.ncbi.nlm.nih.gov/pubmed/24993361", "http://www.ncbi.nlm.nih.gov/pubmed/24152604", "http://www.ncbi.nlm.nih.gov/pubmed/25260362", "http://www.ncbi.nlm.nih.gov/pubmed/22268612", "http://www.ncbi.nlm.nih.gov/pubmed/25598831", "http://www.ncbi.nlm.nih.gov/pubmed/24491572", "http://www.ncbi.nlm.nih.gov/pubmed/26045645", "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "http://www.ncbi.nlm.nih.gov/pubmed/25402275", "http://www.ncbi.nlm.nih.gov/pubmed/23859534", "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "http://www.ncbi.nlm.nih.gov/pubmed/24944269", "http://www.ncbi.nlm.nih.gov/pubmed/23390498", "http://www.ncbi.nlm.nih.gov/pubmed/23940010", "http://www.ncbi.nlm.nih.gov/pubmed/24964723", "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "http://www.ncbi.nlm.nih.gov/pubmed/24622369", "http://www.ncbi.nlm.nih.gov/pubmed/23859488", "http://www.ncbi.nlm.nih.gov/pubmed/21985634", "http://www.ncbi.nlm.nih.gov/pubmed/23253948", "http://www.ncbi.nlm.nih.gov/pubmed/23149871", "http://www.ncbi.nlm.nih.gov/pubmed/24463454", "http://www.ncbi.nlm.nih.gov/pubmed/25775379", "http://www.ncbi.nlm.nih.gov/pubmed/23497760" ], "ideal_answer": [ "Empagliflozin (Jardiance) is a SGLT2 inhibitor." ], "exact_answer": [ "SGLT2" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051273", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051297", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920" ], "type": "factoid", "id": "571e12097de986d80d000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26045645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "AIMS: Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus (T2DM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Effect of food on the pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and assessment of dose proportionality in healthy volunteers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152604", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23149871", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23906374", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859488", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, and metformin following co-administration in healthy volunteers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23253948", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Exposure-response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24964723", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Rationale, design and baseline characteristics of a 4-year (208-week) phase III trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to metformin in patients with type 2 diabetes mellitus with insufficient glycemic control.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24007456", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "By inhibiting reabsorption of glucose from the proximal tubules in the kidney via inhibition of SGLT2, empagliflozin provides a novel insulin-independent mechanism of lowering blood glucose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 675, "text": "Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of treatment for T2DM that reduce hyperglycemia by reducing renal glucose reabsorption and thereby increasing urinary glucose excretion.This paper reviews the pharmacokinetic and pharmacodynamic properties of the SGLT2 inhibitor empagliflozin , the results of clinical trials investigating the efficacy of empagliflozin given as monotherapy or as add-on therapy on glycemic control, body weight, and blood pressure in patients with T2DM, and the safety and tolerability profile of empagliflozin.Empagliflozin offers good glycemic efficacy, weight loss, blood pressure reduction, and a low risk of hypoglycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Oral empagliflozin (Jardiance()), a sodium glucose cotransporter-2 (SGLT2) inhibitor, is a convenient once-daily treatment for adult patients with type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 414, "text": " This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23054692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 499, "text": "Empagliflozin is a potent, oral, selective inhibitor of sodium glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus. The goal of these studies was to investigate potential drug-drug interactions between empagliflozin and gemfibrozil (an organic anion-transporting polypeptide 1B1 [OATP1B1]/1B3 and organic anion transporter 3 [OAT3] inhibitor), rifampicin (an OATP1B1/1B3 inhibitor), or probenecid (an OAT3 and uridine diphosphate glucuronosyltransferase inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24491572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21985634", "endSection": "title" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1621, "text": " Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the highest selectivity window of the tested SGLT-2 inhibitors over hSGLT-1. Empagliflozin represents an innovative therapeutic approach to treat diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21985634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21985634", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859488", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1542, "text": "Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the highest selectivity window of the tested SGLT-2 inhibitors over hSGLT-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21985634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859534", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859488", "endSection": "title" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1127, "text": "Compared with other SGLT-2 inhibitors, empagliflozin has a high degree of selectivity over SGLT-1, 4, 5 and 6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21985634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23149871", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24944269", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Empagliflozin is an orally available, potent and highly selective inhibitor of the sodium glucose cotransporter 2 (SGLT2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23054692", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 414, "text": "Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23054692", "endSection": "abstract" } ] }, { "body": "What symptoms 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"CRANIOSTENOSIS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18014478", "o": "Craniosynostoses [Disease/Finding]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18457000", "o": "Plagiocephalies, Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1305187", "o": "synostosis (cranial)" }, { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "NCI: A rare autosomal dominant inherited disorder caused by mutations in the FGFR3 gene. It is characterized by premature fusion of cranial bones, resulting in head shape abnormalities, flattened cheekbones, and wide-set eyes." } ], "ideal_answer": [ "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition. Tarsal coalition is a distinct feature of Muenke syndrome and has been reported since the initial description of the disorder in the 1990s. ", "Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pansynostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (broad skull), although turribrachycephaly (a \"tower-shaped\" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: ocular hypertelorism, ptosis or proptosis (usually mild), midface hypoplasia, temporal bossing, and a highly arched palate. Strabismus is common. Extracranial findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "summary", "id": "52bf1d3c03868f1b0600000d", "snippets": [ { "offsetInBeginSection": 164, "offsetInEndSection": 481, "text": "Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition. Tarsal coalition is a distinct feature of Muenke syndrome and has been reported since the initial description of the disorder in the 1990s. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Muenke syndrome caused by the FGFR3(P250R) mutation is an autosomal dominant disorder mostly identified with coronal suture synostosis, but it also presents with other craniofacial phenotypes that include mild to moderate midface hypoplasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016144", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1207, "text": "Sensorineural hearing loss at lower frequencies was found only in patients with Muenke syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21844411", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1544, "text": " Sensorineural hearing loss can occur in all 4 syndromes studied but is the primary cause of hearing loss in children and young adults with Muenke syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21844411", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 298, "text": "The facial features of children with FGFR3Pro250Arg mutation (Muenke syndrome) differ from those with the other eponymous craniosynostotic disorders. We documented midfacial growth and position of the forehead after fronto-orbital advancement (FOA) in patients with the FGFR3 mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 1281, "text": "Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pansynostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (broad skull), although turribrachycephaly (a \"tower-shaped\" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: ocular hypertelorism, ptosis or proptosis (usually mild), midface hypoplasia, temporal bossing, and a highly arched palate. Strabismus is common. Extracranial findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 762, "text": "A majority of the patients (95%) demonstrated a mild-to-moderate, low frequency sensorineural hearing loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1222, "text": "Increased digital markings were more severe posteriorly in Muenke patients than in non-Muenke patients. The Muenke patients with unilateral coronal synostosis showed a somewhat more severe asymmetry in the anterior part of the skull than the non-Muenke patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17414289", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 322, "text": "Muenke syndrome is a genetically determined craniosynostosis that involves one or both coronal sutures. In some patients it is associated with skeletal abnormalities such as thimble-like middle phalanges, coned epiphysis, and/or neurological impairment, namely sensorineural hearing loss or mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14963686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3(P250R) ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22622662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 665, "text": "Muenke syndrome and FGFR2-related isolated coronal synostosis are characterized only by uni- or bicoronal craniosynostosis; the remainder are characterized by bicoronal craniosynostosis or cloverleaf skull, distinctive facial features, and variable hand and foot findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301628", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 409, "text": "Muenke syndrome is an autosomal-dominant craniosynostosis syndrome characterized by unilateral or bilateral coronal craniosynostosis, hearing loss, intellectual disability, and relatively subtle limb findings such as carpal bone fusion and tarsal bone fusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446440", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 264, "text": "Muenke syndrome is characterized by coronal suture synostosis, midface hypoplasia, subtle limb anomalies, and hearing loss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 408, "text": "Muenke syndrome is an autosomal-dominant craniosynostosis syndrome characterized by unilateral or bilateral coronal craniosynostosis, hearing loss, intellectual disability, and relatively subtle limb findings such as carpal bone fusion and tarsal bone fusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 339, "text": "Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3(P250R) )", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22622662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" } ] }, { "body": "List all reported treatment options for anxiety in autism spectrum disorder.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18437549", "http://www.ncbi.nlm.nih.gov/pubmed/22964266", "http://www.ncbi.nlm.nih.gov/pubmed/22735897", "http://www.ncbi.nlm.nih.gov/pubmed/23118256", "http://www.ncbi.nlm.nih.gov/pubmed/22588377", "http://www.ncbi.nlm.nih.gov/pubmed/21571763", "http://www.ncbi.nlm.nih.gov/pubmed/17171539", "http://www.ncbi.nlm.nih.gov/pubmed/20694508", "http://www.ncbi.nlm.nih.gov/pubmed/22299802", "http://www.ncbi.nlm.nih.gov/pubmed/22934167" ], "ideal_answer": [ "The predominant approach is to use versions of cognitive behavioural therapies, such as:\nMindfulness Based Therapy (MBT)\nMultimodal Anxiety and Social Skills Intervention (MASSI) program\nmodified version of the Coping Cat program, (cognitive-behavioral therapy; CBT)\nFamily cognitive-behavioral therapy has been found to be more effective than Individual cognitive-behavioral therapy \nConflict management for couples, even when conflict and family distress is low\n\nDrugtherapy: \nSertraline" ], "exact_answer": [ [ "Mindfulness Based Therapy (MBT)" ], [ "Multimodal Anxiety and Social Skills Intervention (MASSI) program" ], [ "modified version of the Coping Cat program", "(cognitive-behavioral therapy; CBT" ], [ "Family cognitive-behavioral therapy" ], [ "Individual cognitive-behavioral therapy" ], [ "Conflict management for couples", "even when conflict and family distress is low" ], [ "Sertraline" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002659", "http://www.disease-ontology.org/api/metadata/DOID:2030", "http://www.disease-ontology.org/api/metadata/DOID:12849", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001007", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001008", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321", "http://www.disease-ontology.org/api/metadata/DOID:0060041" ], "type": "list", "id": "515de993298dcd4e51000024", "snippets": [ { "offsetInBeginSection": 1127, "offsetInEndSection": 1368, "text": "A parent report of comorbid diagnosis of attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, depression, or anxiety was associated with a high rate of use, with 80% receiving \u2265 1 psychotropic medication", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118256", "endSection": "sections.0" }, { "offsetInBeginSection": 129, "offsetInEndSection": 269, "text": "Mindfulness-based therapy (MBT) has been found effective in reducing anxiety and depression symptoms, however research in autism is limited.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22964266", "endSection": "sections.0" }, { "offsetInBeginSection": 270, "offsetInEndSection": 377, "text": "Therefore, we examined the effects of a modified MBT protocol (MBT-AS) in high-functioning adults with ASD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22964266", "endSection": "sections.0" }, { "offsetInBeginSection": 715, "offsetInEndSection": 823, "text": "the present study is the first controlled trial to demonstrate that adults with ASD can benefit from MBT-AS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22964266", "endSection": "sections.0" }, { "offsetInBeginSection": 167, "offsetInEndSection": 423, "text": "This pilot, randomized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention (MASSI) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735897", "endSection": "sections.0" }, { "offsetInBeginSection": 736, "offsetInEndSection": 833, "text": "These findings suggest MASSI is a feasible treatment program and further evaluation is warranted.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735897", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder (ASD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22588377", "endSection": "sections.0" }, { "offsetInBeginSection": 315, "offsetInEndSection": 373, "text": "the Coping Cat program (cognitive-behavioral therapy; CBT)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22588377", "endSection": "sections.0" }, { "offsetInBeginSection": 572, "offsetInEndSection": 791, "text": "Results provide preliminary evidence that a modified version of the Coping Cat program may be a feasible and effective program for reducing clinically significant levels of anxiety in children with high-functioning ASD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22588377", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 313, "text": "The intent of this article is to explore the efficacy of both the literal and concrete externalization aspects within narrative therapy, and the implementation of interactive metaphors as a combined psychotherapeutic approach for decreasing anxiety with people who present with high-functioning autism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22299802", "endSection": "sections.0" }, { "offsetInBeginSection": 752, "offsetInEndSection": 989, "text": "This paper reports a case series of children and adolescents with ASD and an anxiety disorder who were treated with a standard cognitive behaviour therapy (CBT) rationale adapted to take account of the neuropsychological features of ASD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21571763", "endSection": "sections.0" }, { "offsetInBeginSection": 249, "offsetInEndSection": 408, "text": "children with moderate autistic symptomology (per SRS-P) were significantly more likely to improve from family CBT (FCBT) than individual CBT (ICBT; OR\u00a0=\u00a08.67)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20694508", "endSection": "sections.0" }, { "offsetInBeginSection": 653, "offsetInEndSection": 850, "text": "Though both treatments reduced anxiety, FCBT outperformed ICBT for children with moderate ASD symptoms, a benefit potentially linked to more at-home exposures and greater child involvement in FCBT.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20694508", "endSection": "sections.0" }, { "offsetInBeginSection": 412, "offsetInEndSection": 577, "text": "A structural model-building approach was used to test the extent to which family and peer variables directly or indirectly affected ASD via child anxiety/depression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437549", "endSection": "sections.0" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1297, "text": "The key findings were that anxiety/depression and ASD symptomatology were significantly related, and family conflict was more predictive of ASD symptomatology than positive family/peer influences. The results point to the utility of expanding interventions to include conflict management for couples, even when conflict and family distress is low.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437549", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "A family-based, cognitive behavioural treatment for anxiety in 47 children with comorbid anxiety disorders and High Functioning Autism Spectrum Disorder (HFA) was evaluated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17171539", "endSection": "sections.0" }, { "offsetInBeginSection": 402, "offsetInEndSection": 674, "text": "Following treatment, 71.4% of the treated participants no longer fulfilled diagnostic criteria for an anxiety disorder. Comparisons between the two conditions indicated significant reductions in anxiety symptoms as measured by self-report, parent report and teacher report", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17171539", "endSection": "sections.0" } ] }, { "body": "List adenosine A2A receptor antagonists that are used for Parkinson's disease treatment.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23748382", "http://www.ncbi.nlm.nih.gov/pubmed/20182024", "http://www.ncbi.nlm.nih.gov/pubmed/24687255", "http://www.ncbi.nlm.nih.gov/pubmed/15298067", "http://www.ncbi.nlm.nih.gov/pubmed/22585137", "http://www.ncbi.nlm.nih.gov/pubmed/25175961", "http://www.ncbi.nlm.nih.gov/pubmed/15974638", "http://www.ncbi.nlm.nih.gov/pubmed/23483627", "http://www.ncbi.nlm.nih.gov/pubmed/16004599", "http://www.ncbi.nlm.nih.gov/pubmed/23642267" ], "ideal_answer": [ "Istradefylline and preladenant are adenosine A2A receptor antagonists that are used for Parkinson's disease treatment." ], "exact_answer": [ [ "istradefylline" ], [ "preladenant" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058917", "http://www.disease-ontology.org/api/metadata/DOID:14330", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300" ], "type": "list", "id": "54fc9b236ad7dcbc12000005", "snippets": [ { "offsetInBeginSection": 177, "offsetInEndSection": 323, "text": "Adenosine A2A antagonists, such as istradefylline, improve motor function in PD, but their effect on cognitive impairment has not been determined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23748382", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 995, "text": "Both istradefylline and preladenant have demonstrated moderate efficacy in reducing off time in PD patients with motor fluctuations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22585137", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1310, "text": " The available data also suggest that caffeine can improve the motor deficits of PD and that adenosine A2A receptor antagonists such as istradefylline reduces OFF time and dyskinesia associated with standard 'dopamine replacement' treatments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20182024", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1228, "text": "Istradefylline (KW-6002) is the first of several adenosine A2A receptor antagonists in development for PD to advance to phase III clinical trials. Initial studies indicate that in patients with motor fluctuations on levodopa, addition of istradefylline reduces 'off' time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15974638", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1240, "text": "These include alpha2 adrenergic receptor antagonists (eg, fipamezole), adenosine A2A receptor antagonists (eg, istradefylline), AMPA receptor antagonists (eg, talampanel), neuronal synchronization modulators (eg, levetiracetam) and agents that interact with serotonergic systems such as 5-hydroxytryptamine (5-HT)1A agonists (eg, sarizotan) and 5-HT2A antagonists (eg, quetiapine). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15298067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "BACKGROUND: We evaluated the efficacy and safety of istradefylline, a selective adenosine A2A receptor antagonist administered as adjunctive treatment to levodopa for 12 weeks in a double-blind manner in Parkinsons disease patients with motor complications in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23483627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinsons disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16004599", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16004599", "endSection": "title" }, { "offsetInBeginSection": 431, "offsetInEndSection": 606, "text": "In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23642267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23642267", "endSection": "title" } ] }, { "body": "What is the clinical indication of cardiac T1 mapping magnetic resonance?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23564562", "http://www.ncbi.nlm.nih.gov/pubmed/22720998", "http://www.ncbi.nlm.nih.gov/pubmed/24058912", "http://www.ncbi.nlm.nih.gov/pubmed/24518490", "http://www.ncbi.nlm.nih.gov/pubmed/24036385", "http://www.ncbi.nlm.nih.gov/pubmed/24566951", "http://www.ncbi.nlm.nih.gov/pubmed/25310419", "http://www.ncbi.nlm.nih.gov/pubmed/23403334", "http://www.ncbi.nlm.nih.gov/pubmed/17896383", "http://www.ncbi.nlm.nih.gov/pubmed/23549230", "http://www.ncbi.nlm.nih.gov/pubmed/22279111", "http://www.ncbi.nlm.nih.gov/pubmed/24425501", "http://www.ncbi.nlm.nih.gov/pubmed/24931636", "http://www.ncbi.nlm.nih.gov/pubmed/21974927", "http://www.ncbi.nlm.nih.gov/pubmed/23071146", "http://www.ncbi.nlm.nih.gov/pubmed/23349348", "http://www.ncbi.nlm.nih.gov/pubmed/23643513", "http://www.ncbi.nlm.nih.gov/pubmed/24903343", "http://www.ncbi.nlm.nih.gov/pubmed/17659622", "http://www.ncbi.nlm.nih.gov/pubmed/22967246", "http://www.ncbi.nlm.nih.gov/pubmed/19007595", "http://www.ncbi.nlm.nih.gov/pubmed/24011774", "http://www.ncbi.nlm.nih.gov/pubmed/23272704", "http://www.ncbi.nlm.nih.gov/pubmed/24043965", "http://www.ncbi.nlm.nih.gov/pubmed/23408722", "http://www.ncbi.nlm.nih.gov/pubmed/12765114", "http://www.ncbi.nlm.nih.gov/pubmed/22161952", "http://www.ncbi.nlm.nih.gov/pubmed/22309452", "http://www.ncbi.nlm.nih.gov/pubmed/22710483", "http://www.ncbi.nlm.nih.gov/pubmed/25424139", "http://www.ncbi.nlm.nih.gov/pubmed/23845576", "http://www.ncbi.nlm.nih.gov/pubmed/24576837", "http://www.ncbi.nlm.nih.gov/pubmed/24472162", "http://www.ncbi.nlm.nih.gov/pubmed/23280998", "http://www.ncbi.nlm.nih.gov/pubmed/23890156", "http://www.ncbi.nlm.nih.gov/pubmed/24124732", "http://www.ncbi.nlm.nih.gov/pubmed/23498672", "http://www.ncbi.nlm.nih.gov/pubmed/22903654", "http://www.ncbi.nlm.nih.gov/pubmed/23498674" ], "ideal_answer": [ "T1 mapping can quantitatively characterize myocardial tissue, in particular diffuse and interstitial fibrosis, edema in both overt and subclinical cardiophyopathies. However more research is required before a large-scale application for clinical decision-making can be recommended.", "The clinical indication of cardiac T1 mapping magnetic resonance is the detection of diffuse myocardial fibrosis in nonischemic cardiomyopathies" ], "exact_answer": [ "detection of myocardial fibrosis in nonischemic cardiomyopathies", "T1 mapping can quantitatively characterize myocardial tissue, i.e. fibrosis and edema." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321" ], "type": "factoid", "id": "533ba218fd9a95ea0d000007", "snippets": [ { "offsetInBeginSection": 504, "offsetInEndSection": 671, "text": "More diverse patterns of late enhancement including patchy, mid-wall, subepicardial, or diffuse enhancement are of interest in diagnosing nonischemic cardiomyopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903654", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1339, "text": "Methods for quantification of T1 and extracellular volume fraction are emerging to tackle the issue of discriminating globally diffuse fibrosis from normal healthy tissue which is challenging using conventional late enhancement methods. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903654", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 593, "text": "Recent T1 mapping techniques aim to overcome the limitations of late gadolinium enhancement to assess diffuse fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058912", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1432, "text": "T1 mapping techniques performed both with and without contrast are enabling quantification of diffuse myocardial fibrosis and myocardial infiltration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845576", "endSection": "abstract" }, { "offsetInBeginSection": 1857, "offsetInEndSection": 2094, "text": "Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac AL amyloidosis, correlates well with markers of systolic and diastolic dysfunction, and is potentially more sensitive for detecting early disease than LGE imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23498672", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 544, "text": "T1 mapping has been proposed as potentially valuable in the quantitative assessment of diffuse myocardial fibrosis, but no studies to date have systematically evaluated its role in the differentiation of healthy myocardium from diffuse disease in a clinical setting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23498674", "endSection": "abstract" }, { "offsetInBeginSection": 2141, "offsetInEndSection": 2318, "text": "This study demonstrates that native and post-contrast T1 values provide indexes with high diagnostic accuracy for the discrimination of normal and diffusely diseased myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23498674", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1646, "text": "T1 values lengthened with greater LVMI and correlated with the degree of biopsy-quantified fibrosis. This may provide a useful clinical assessment of diffuse myocardial fibrosis in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349348", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 115, "text": "Cardiac magnetic resonance (CMR) T1 mapping has been used to characterize myocardial diffuse fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272704", "endSection": "abstract" }, { "offsetInBeginSection": 1846, "offsetInEndSection": 1986, "text": "In HCM and DCM, noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071146", "endSection": "abstract" } ] }, { "body": "Which autophagy pathway is trigered by the KFERQ motif of cytosolic proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15149326", "http://www.ncbi.nlm.nih.gov/pubmed/24477641", "http://www.ncbi.nlm.nih.gov/pubmed/23452232", "http://www.ncbi.nlm.nih.gov/pubmed/16209346", "http://www.ncbi.nlm.nih.gov/pubmed/10938088", "http://www.ncbi.nlm.nih.gov/pubmed/12105396", "http://www.ncbi.nlm.nih.gov/pubmed/19433452", "http://www.ncbi.nlm.nih.gov/pubmed/23880665", "http://www.ncbi.nlm.nih.gov/pubmed/23070014", "http://www.ncbi.nlm.nih.gov/pubmed/24323530", "http://www.ncbi.nlm.nih.gov/pubmed/16782460", "http://www.ncbi.nlm.nih.gov/pubmed/23404999", "http://www.ncbi.nlm.nih.gov/pubmed/11262416" ], "ideal_answer": [ "Cytosolic proteins carrying the KFERQ motif (a specific lysosomal import consensus sequence) are directed to a selective form of lysosomal degradation, called chaperone-mediated autophagy (CMA), as chaperone protein Hsc73 and other chaperones are involved in this process." ], "exact_answer": [ "chaperone-mediated autophagy (CMA)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054730", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343" ], "type": "factoid", "id": "5540fbce234c5a7c75000001", "snippets": [ { "offsetInBeginSection": 304, "offsetInEndSection": 428, "text": "Chaperone-mediated autophagy (CMA) is a selective form of lysosomal degradation targeting proteins carrying the KFERQ motif.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452232", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 354, "text": "The significance of the receptor glycoprotein lamp2a in the chaperone-mediated autophagy of cytosolic proteins with KFERQ motif has been described in details as well as the chaperone protein Hsc73 and other chaperones involved in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16209346", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 448, "text": "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11262416", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 353, "text": "The significance of the receptor glycoprotein lamp2a in the chaperone-mediated autophagy of cytosolic proteins with KFERQ motif has been described in details as well as the chaperone protein Hsc73 and other chaperones involved in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16209346", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 445, "text": "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11262416", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 420, "text": "Chaperone-mediated autophagy (CMA) is a selective form of lysosomal degradation targeting proteins carrying the KFERQ motif.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404999", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1234, "text": "The abundance of proteins containing that chaperone-mediated autophagy KFERQ signal motif increased 38% and individual KFERQ containing proteins [e.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15149326", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1175, "text": "Furthermore, four annexins containing KFERQ-like sequences, annexins I, II, IV, and VI, are enriched in lysosomes with high chaperone-mediated autophagy activity as expected for substrate proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10938088", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 861, "text": "Using isolated lysosomes, only the annexins containing KFERQ-like sequences are degraded by chaperone mediated-autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10938088", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1425, "text": "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23070014", "endSection": "abstract" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1432, "text": "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23070014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "AIMS: Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404999", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 447, "text": "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11262416", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 353, "text": "The significance of the receptor glycoprotein lamp2a in the chaperone-mediated autophagy of cytosolic proteins with KFERQ motif has been described in details as well as the chaperone protein Hsc73 and other chaperones involved in this process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16209346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404999", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 946, "text": "In cell culture, growth factors suppress the lysosomal pathway of chaperone-mediated autophagy leading to the accumulation of specific cytoplasmic proteins containing KFERQ motifs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12105396", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 446, "text": "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11262416", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1346, "text": "The abundance of proteins containing that chaperone-mediated autophagy KFERQ signal motif increased 38% and individual KFERQ containing proteins [e.g., M2 pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pax2] were more abundant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15149326", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1303, "text": "These results provide striking evidence for the importance of KFERQ motifs in substrates of chaperone-mediated autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10938088", "endSection": "abstract" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1431, "text": "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23070014", 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A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease. TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation." ], "exact_answer": [ [ "Brain lesions" ], [ "Kidney lesions" ], [ "Lung lesions" ], [ "renal angiomyolipoma" ], [ "subependymal giant cell astrocytoma (SEGA)" ], [ "seizures" ], [ "mental detardation" ], [ "autism" ], [ "hepatic lesions" ], [ "Pulmonary lymphangioleiomyomatosis" ] ], "concepts": [ "http://www.uniprot.org/uniprot/TSC2_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://www.uniprot.org/uniprot/TSC1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012598", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC1_SCHPO", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.uniprot.org/uniprot/TSC2_SCHPO", "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ], "type": "list", "id": "52f77f042059c6d71c000029", "snippets": [ { "offsetInBeginSection": 1346, "offsetInEndSection": 1448, "text": "Most cases of tuberous sclerosis complex are complicated with bilateral multiple renal angiomyolipoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24169285", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1147, "text": "Periodic imaging surveillance for development of subependymal giant cell astrocytoma (SEGA), preferably by magnetic resonance imaging (MRI) every 1-3\u00a0years, is now standard of care", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23852707", "endSection": "abstract" }, { "offsetInBeginSection": 1689, "offsetInEndSection": 1935, "text": " Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23274119", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 603, "text": "Hepatic angiomyolipomas (AML), cysts, and other benign lesions were identified in 30% of the cohort, and some lesions grew significantly over time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22251200", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 698, "text": "Pulmonary lymphangioleiomyomatosis and bilateral renal angiomyolipomas are some presentations of tuberous sclerosis and the coexistence of both conditions may cause devastating morbidity and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20184711", "endSection": "abstract" }, { "offsetInBeginSection": 58, "offsetInEndSection": 356, "text": "uberous sclerosis, a genetic, rare, variably expressed disease. Clinical symptoms were chest pain, and progressive dyspnea. Computed tomography scan of the chest showed bilateral, diffuse, small thin-walled cysts scattered throughout the lungs characteristic for pulmonary lymphangioleiomyomatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20184711", "endSection": "abstract" } ] }, { "body": "How does dabigatran therapy affect aPTT in patients with atrial fibrillation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23100377", "http://www.ncbi.nlm.nih.gov/pubmed/23784008", "http://www.ncbi.nlm.nih.gov/pubmed/22608344", "http://www.ncbi.nlm.nih.gov/pubmed/22539097", "http://www.ncbi.nlm.nih.gov/pubmed/23680005", "http://www.ncbi.nlm.nih.gov/pubmed/24151507", "http://www.ncbi.nlm.nih.gov/pubmed/22398858", "http://www.ncbi.nlm.nih.gov/pubmed/22293451" ], "ideal_answer": [ "Dabigatran increases aPTT in patients with atrial fibrillation, although aPTT does not respond linearily to dabigatran therapy." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001281", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010314", "http://www.biosemantics.org/jochem#4242811" ], "type": "summary", "id": "532f06e6d6d3ac6a34000028", "snippets": [ { "offsetInBeginSection": 549, "offsetInEndSection": 821, "text": "He had been started on dabigatran 150\u2009mg twice a day about 4 months ago as an outpatient by his cardiologist. His prothrombin time (PT) was 63 seconds with international normalized ratio (INR) of 8.8 and his activated partial thromboplastin time (aPTT) was 105.7 seconds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24151507", "endSection": "abstract" }, { "offsetInBeginSection": 1754, "offsetInEndSection": 1898, "text": "The aPTT assay is relatively insensitive to dabigatran, and normal aPTT results may be observed even with therapeutic dabigatran concentrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23784008", "endSection": "abstract" }, { "offsetInBeginSection": 1642, "offsetInEndSection": 1925, "text": "The APTT values became prolonged under dabigatran usage and exhibited a remarkable diversity. Although major bleeding did not occur unless APTT was prolonged excessively, minor bleeding arose irrespective of the APTT values even within the range of the APTT values not exceeding 80s.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23680005", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 1096, "text": "Dabigatran led to a dose-dependent prolongation of the clotting times in coagulometric tests and influenced the majority of the parameters measured. Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100377", "endSection": "abstract" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1579, "text": "Although aPTT does not provide a linear response to dabigatran therapy, the presence of a completely normal PTT may exclude therapeutic dabigatran anticoagulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22608344", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 623, "text": "Commonly available global coagulation time assessments (e.g. prothrombin time and activated partial thromboplastin time) are highly influenced by rivaroxaban and dabigatran but these assays are relatively insensitive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22539097", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1143, "text": "The relationship between dabigatran plasma concentrations and activated partial thromboplastin time in healthy volunteers and patients (n=762) was best described with a combination of a linear model and a maximum effect (Emax) model, consistent with previous reports. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22398858", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 707, "text": "We found a wide distribution of APTT in NVAF patients under dabigatran treatment. High APTT might help screen for bleeding risks among patients under dabigatran, but requires future investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22293451", "endSection": "abstract" } ] }, { "body": "List fish anti-freeze proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19857362", "http://www.ncbi.nlm.nih.gov/pubmed/23479899", "http://www.ncbi.nlm.nih.gov/pubmed/17189482", "http://www.ncbi.nlm.nih.gov/pubmed/10405170", "http://www.ncbi.nlm.nih.gov/pubmed/15059666", "http://www.ncbi.nlm.nih.gov/pubmed/16297800", "http://www.ncbi.nlm.nih.gov/pubmed/12065219", "http://www.ncbi.nlm.nih.gov/pubmed/17553775", "http://www.ncbi.nlm.nih.gov/pubmed/11240367", "http://www.ncbi.nlm.nih.gov/pubmed/15146494", "http://www.ncbi.nlm.nih.gov/pubmed/22180206" ], "ideal_answer": [ "AFP-I\nAFP-II\nAFP-III\nAnti-freeze glycoprotein\nThermal hysteresis protein" ], "exact_answer": [ [ "anti-freeze protein-3", "AFP-III" ], [ "anti-freeze glycoprotein" ], [ "Thermal hysteresis protein" ], [ "AFP-I" ], [ "AFP-II" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050826", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009409", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005615", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033637" ], "type": "list", "id": "54fe09036ad7dcbc12000009", "snippets": [ { "offsetInBeginSection": 713, "offsetInEndSection": 780, "text": "the anti-freeze glycoprotein of Antarctic and Arctic notothenoids, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22180206", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 86, "text": "pe III anti-freeze protein (AFP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17189482", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 308, "text": "AFP I or AFP III", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16297800", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 975, "text": "type III anti-freeze proteins ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15146494", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 356, "text": "wild type III thermal hysteresis protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15059666", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 338, "text": "Thermal hysteresis proteins (THPs) have been found in vertebrates, invertebrates, plants, bacteria and fungi and are able to depress the freezing point of water (in the presence of ice crystals) in a non-colligative manner by binding to the surface of nascent ice crystals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11240367", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 424, "text": "skin-type anti-freeze protein-3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405170", "endSection": "abstract" } ] }, { "body": "Which is the phosphorylated residue in the promoter paused form of RNA polymerase II?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8015613", "http://www.ncbi.nlm.nih.gov/pubmed/23064645", "http://www.ncbi.nlm.nih.gov/pubmed/17942706", "http://www.ncbi.nlm.nih.gov/pubmed/12612070", "http://www.ncbi.nlm.nih.gov/pubmed/21095588", "http://www.ncbi.nlm.nih.gov/pubmed/21385935", "http://www.ncbi.nlm.nih.gov/pubmed/23087403", "http://www.ncbi.nlm.nih.gov/pubmed/14560008" ], "ideal_answer": [ "The promoter paused form of RNA polymerase II is phosphorylated on serine 5 residues of the C-terminal heptapeptide repeat domain (CTD) of the largest subunit." ], "exact_answer": [ "Serine 5" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012319", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071620", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071619" ], "type": "factoid", "id": "5343bdd6aeec6fbd07000001", "snippets": [ { "offsetInBeginSection": 1239, "offsetInEndSection": 1394, "text": "increase levels of serine-5 phosphorylated RNA polymerase II in the mutation target region, consistent with an effect on transcriptional elongation/pausing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23087403", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 912, "text": "pol-II accumulated in the 5'-region of the gene, which indicated postinitiation pausing. pol-II binding, 5'-accumulation, C-terminal domain Ser-5 and Ser-2 phosphorylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21385935", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 852, "text": "The carboxy-terminal domain of the paused polymerase large subunit is hyperphosphorylated on serine 5, and phosphorylation of serine 2 is first detected here", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21095588", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 697, "text": "the promoter-paused form of Pol II (Pol IIo(ser5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942706", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 648, "text": "Pause release depends on Cdk9-cyclin T1 (P-TEFb); Cdk7 is also required for Cdk9-activating phosphorylation and Cdk9-dependent downstream events--Pol II C-terminal domain Ser2 phosphorylation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064645", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 749, "text": "For genes containing a 5' paused polymerase, passage of the paused RNA polymerase into an elongationally competent mode in vivo coincides with phosphorylation of the CTD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8015613", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 815, "text": "Ser-5 phosphorylation of Pol II is concentrated near the promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12612070", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 630, "text": "the promoter-paused Pol II shows Ser5 but not Ser2 phosphorylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14560008", "endSection": "abstract" } ] }, { "body": "Has overexpression of sirtuins been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12006491", "http://www.ncbi.nlm.nih.gov/pubmed/21938067", "http://www.ncbi.nlm.nih.gov/pubmed/15308206", "http://www.ncbi.nlm.nih.gov/pubmed/23082874" ], "ideal_answer": [ "Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/SIR2_MOUSE", "http://www.uniprot.org/uniprot/SIR2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004718", "http://www.uniprot.org/uniprot/SIR6_HUMAN", "http://www.uniprot.org/uniprot/SIR3_MOUSE", "http://www.uniprot.org/uniprot/SIR7_HUMAN", "http://www.uniprot.org/uniprot/SIR6_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015003", "http://www.uniprot.org/uniprot/SIR2_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037761", "http://www.uniprot.org/uniprot/SIR2_DANRE", "http://www.uniprot.org/uniprot/SIR7_MOUSE", "http://www.uniprot.org/uniprot/SIR4_HUMAN", "http://www.uniprot.org/uniprot/SIR4_BOVIN", "http://www.uniprot.org/uniprot/SIR1_HUMAN", "http://www.uniprot.org/uniprot/SIR7_BOVIN", "http://www.uniprot.org/uniprot/SIR2_RAT", "http://www.uniprot.org/uniprot/SIR4_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056564", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056565", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056566", "http://www.uniprot.org/uniprot/SIR1_MOUSE", "http://www.uniprot.org/uniprot/SIR2_MACFA" ], "type": "yesno", "id": "52b2e97df828ad283c000012", "snippets": [ { "offsetInBeginSection": 1007, "offsetInEndSection": 1117, "text": "In addition, Sir2 overexpression prevents Rif1 deletion from disrupting Sir2 at IGS1 and shortening lifespan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23082874", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 169, "text": "Roles for sirtuin proteins at telomeres are thought to promote lifespan in yeast and mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23082874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21938067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15308206", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 813, "text": "When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12006491", "endSection": "abstract" } ] }, { "body": "Name the major classes of small non coding RNAs in mammalians?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20823303", "http://www.ncbi.nlm.nih.gov/pubmed/19908360" ], "ideal_answer": [ "microRNAs (miRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs) are the major classes of small non coding RNAs. Recently, thanks mostly to massively parallel sequencing technologies, other classes of small RNAs have been discovered, such as piRNAs and scaRNAs." ], "exact_answer": [ [ "miRNA" ], [ "snRNA" ], [ "snoRNAs" ], [ "scaRNAs" ], [ "piRNAS" ] ], "type": "list", "id": "517295c18ed59a060a000016", "snippets": [ { "offsetInBeginSection": 292, "offsetInEndSection": 429, "text": "Some of these RNA classes, in particular microRNAs and snoRNAs, undergo maturation processes that lead to the production of shorter RNAs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19908360", "endSection": "sections.0" } ] }, { "body": "Describe a diet that reduces the chance of kidney stones.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23302672", "http://www.ncbi.nlm.nih.gov/pubmed/23546565", "http://www.ncbi.nlm.nih.gov/pubmed/23593205", "http://www.ncbi.nlm.nih.gov/pubmed/23880796", "http://www.ncbi.nlm.nih.gov/pubmed/23535174", "http://www.ncbi.nlm.nih.gov/pubmed/24127678", "http://www.ncbi.nlm.nih.gov/pubmed/22857835", "http://www.ncbi.nlm.nih.gov/pubmed/24026180", "http://www.ncbi.nlm.nih.gov/pubmed/16174292", "http://www.ncbi.nlm.nih.gov/pubmed/23221031", "http://www.ncbi.nlm.nih.gov/pubmed/23732207", "http://www.ncbi.nlm.nih.gov/pubmed/21369385", "http://www.ncbi.nlm.nih.gov/pubmed/23634702", "http://www.ncbi.nlm.nih.gov/pubmed/11269613", "http://www.ncbi.nlm.nih.gov/pubmed/23674806", "http://www.ncbi.nlm.nih.gov/pubmed/23568066", "http://www.ncbi.nlm.nih.gov/pubmed/23438422", "http://www.ncbi.nlm.nih.gov/pubmed/14552081", "http://www.ncbi.nlm.nih.gov/pubmed/23827660" ], "triples": [ { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13727389", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13688679", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13725651", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13688680", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13903830", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13816280", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13688678", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" } ], "ideal_answer": [ "People can help prevent kidney stones by making changes in fluid intake and, depending on the type of kidney stone, changes in consumption of sodium, animal protein, calcium, and oxalate.\nDrinking enough fluids each day is the best way to help prevent most types of kidney stones. Health care providers recommend that a person drink 2 to 3 liters of fluid a day. People with cystine stones may need to drink even more. Though water is best, other fluids may also help prevent kidney stones, such as citrus drinks." ], "exact_answer": [ "reducing sodium" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007669", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007668", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014545", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014676", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007674", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004035", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018753", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004032", "http://www.disease-ontology.org/api/metadata/DOID:585" ], "type": "factoid", "id": "5311bcc2e3eabad021000005", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 727, "text": "calcium oxalate remains the dominant type accounting for 64% of stones in our dataset,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24127678", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 849, "text": "Uric acid stones contributed 16% of contemporary stone compositions,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24127678", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1015, "text": "Struvite stones showed a decreasing trend from 14% in the 1970s, to 12% in the 1980s and 7% in the current data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24127678", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 263, "text": ". Given recent concerns that calcium supplements may raise risk for cardiovascular disease and kidney stones,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880796", "endSection": "abstract" } ] }, { "body": "What pharmacological and non-pharmacological interventions can be considered as prophylactic therapies in Cluster Headache patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11252143", "http://www.ncbi.nlm.nih.gov/pubmed/16628535", "http://www.ncbi.nlm.nih.gov/pubmed/15651299", "http://www.ncbi.nlm.nih.gov/pubmed/21284609", "http://www.ncbi.nlm.nih.gov/pubmed/17901920", "http://www.ncbi.nlm.nih.gov/pubmed/11026146", "http://www.ncbi.nlm.nih.gov/pubmed/2520442", "http://www.ncbi.nlm.nih.gov/pubmed/12390644", "http://www.ncbi.nlm.nih.gov/pubmed/20352587", "http://www.ncbi.nlm.nih.gov/pubmed/16041199" ], "ideal_answer": [ "Verapamil, a calcium channel blocker, is considered the mainstay of prophylactic therapy of Cluster Headache patients. Lithium carbonate, topiramate, valproic acid, gabapentin, baclofen, methysergide, melatonin, ketoprofen and indomethacin can also be tried for prophylactic therapy of Cluster Headaches patients. Non-pharmacological prophylactic measures, such as peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation, ablative surgery, and botulinum toxin type-A (BTX-A) injection, can be also considered." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003027", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055502" ], "type": "summary", "id": "5148a2f6d24251bc05000035", "snippets": [ { "offsetInBeginSection": 563, "offsetInEndSection": 767, "text": "The calcium channel blocker verapamil is the drug of choice for CH prevention. Other drugs that may be used for this purpose include lithium carbonate, topiramate, valproic acid, gabapentin, and baclofen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21284609", "endSection": "sections.0" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1149, "text": "Recently, the therapeutic options for refractory CH patients have expanded with the emergence of both peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21284609", "endSection": "sections.0" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1244, "text": "With the emergence of these novel treatments, the role of ablative surgery in CH has declined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21284609", "endSection": "sections.0" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1338, "text": "The mainstay of prophylactic therapy is verapamil. Yet, other medications, including lithium, divalproex sodium, topiramate, methysergide, gabapentin, and even indomethacin, may be useful when the headache fails to respond to verapamil.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20352587", "endSection": "sections.0" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1471, "text": "For medically refractory patients, surgical interventions, occipital nerve stimulation, and deep brain stimulation remain an option.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20352587", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The objective of this open single-centre study was to evaluate the efficacy and tolerability of botulinum toxin type-A (BTX-A) as add-on in the prophylactic treatment of cluster headache (CH).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17901920", "endSection": "sections.0" }, { "offsetInBeginSection": 829, "offsetInEndSection": 973, "text": "These findings provide evidence that BTX-A may be beneficial as an add-on prophylactic therapy for a limited number of patients with chronic CH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17901920", "endSection": "sections.0" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1397, "text": "There are a variety of different medications for abortive and prophylactic therapy, accompanied by a variable amount of evidence-based medicine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16041199", "endSection": "sections.0" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1639, "text": "Most procedures are directed against the sensory trigeminal nerve and associated ganglia, eg, anesthetizing the sphenopalatine ganglion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16041199", "endSection": "sections.0" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1172, "text": "The mainstay of prophylactic therapy is verapamil. Lithium, divalproex sodium, or topiramate may also be useful.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16628535", "endSection": "sections.0" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1299, "text": "Based on our clinical experience, we recommended the combination of nasal sumatriptan for acute attacks and verapamil 240 mg/day for prophylaxis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15651299", "endSection": "sections.0" }, { "offsetInBeginSection": 3204, "offsetInEndSection": 3308, "text": "Topiramate also appears to be well tolerated and useful in the adjunctive treatment of cluster headache.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12390644", "endSection": "sections.0" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1276, "text": "The cornerstone of maintenance prophylaxis is verapamil, yet methysergide, lithium, and divalproex sodium may also be employed. In some patients, melatonin or topiramate may be useful adjunctive therapies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11252143", "endSection": "sections.0" }, { "offsetInBeginSection": 600, "offsetInEndSection": 685, "text": "Prophylactic therapy in most cases consisted of verapamil, also with a good response.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11026146", "endSection": "sections.0" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1079, "text": "Patients with chronic cluster headache may achieve good results from long-term treatment with other therapies, including lithium carbonate, verapamil, and ketoprofen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2520442", "endSection": "sections.0" } ] }, { "body": "How does phospholamban affect the biological activity of the calcium ATPase SERCA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23308118", "http://www.ncbi.nlm.nih.gov/pubmed/15781867", "http://www.ncbi.nlm.nih.gov/pubmed/22679139", "http://www.ncbi.nlm.nih.gov/pubmed/24101520", "http://www.ncbi.nlm.nih.gov/pubmed/21576492", "http://www.ncbi.nlm.nih.gov/pubmed/19708671" ], "ideal_answer": [ "SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum. Based on structural and dynamics data, a model in which PLN undergoes allosteric activation upon encountering SERCA has been proposed. The allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation of PLN shifts the populations toward the B state, increasing SERCA activity. Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure." ], "concepts": [ "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053498" ], "type": "summary", "id": "54fd5dd86ad7dcbc12000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23308118", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 660, "text": "SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22679139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19708671", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 346, "text": "Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15781867", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1538, "text": "Based on structural and dynamics data, we propose a model in which PLN undergoes allosteric activation upon encountering SERCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15781867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. \u03b2-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101520", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 939, "text": "We found that the allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation at Ser-16 of PLN shifts the populations toward the B state, increasing SERCA activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576492", "endSection": "abstract" } ] }, { "body": "List the components of mTOR Complex 2 (mTORC2).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23455608", "http://www.ncbi.nlm.nih.gov/pubmed/22820188", "http://www.ncbi.nlm.nih.gov/pubmed/22595285", "http://www.ncbi.nlm.nih.gov/pubmed/22678916", "http://www.ncbi.nlm.nih.gov/pubmed/23049074", "http://www.ncbi.nlm.nih.gov/pubmed/22532249", "http://www.ncbi.nlm.nih.gov/pubmed/24077282", "http://www.ncbi.nlm.nih.gov/pubmed/23673367", "http://www.ncbi.nlm.nih.gov/pubmed/22773877", "http://www.ncbi.nlm.nih.gov/pubmed/24244675" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10789460", "o": "C39159" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "mTOR Signaling Pathway" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A10789460" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "C39159" } ], "ideal_answer": [ "Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/G\u03b2L and PRR5." ], "exact_answer": [ [ "mTOR" ], [ "Rictor" ], [ "mSin1" ], [ "mLST8/G\u03b2L" ], [ "PRR5" ] ], "concepts": [ "http://www.uniprot.org/uniprot/MTOR_MOUSE", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://www.uniprot.org/uniprot/MTOR_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070438" ], "type": "list", "id": "5505c9008e1671127b000002", "snippets": [ { "offsetInBeginSection": 104, "offsetInEndSection": 192, "text": "mTOR is the major component of two protein complexes: mTOR complex 1 (mTORC1) and mTORC2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24077282", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 259, "text": " Rictor, an mTORC2-specific component", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244675", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 960, "text": "f Rictor (rapamycin-insensitive companion of mTOR), an mTORC2 component,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23673367", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 398, "text": " The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23455608", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 690, "text": " Rictor, a key component of mTORC2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23049074", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 841, "text": "SIN1, a key component of mTOR complex 2 (mTORC2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820188", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 218, "text": " the essential mTORC2 component rictor ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773877", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 203, "text": "Sin1 is an essential component of mTOR complex 2 (mTORC2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22678916", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 844, "text": " SIN1 or Rictor, two key components of mTOR complex 2 (mTORC2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22595285", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 297, "text": " Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/G\u03b2L and PRR5 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22532249", "endSection": "abstract" } ] }, { "body": "What is known about the Digit Ratio (2D:4D) cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23218867", "http://www.ncbi.nlm.nih.gov/pubmed/23146972", "http://www.ncbi.nlm.nih.gov/pubmed/24677324", "http://www.ncbi.nlm.nih.gov/pubmed/20633006", "http://www.ncbi.nlm.nih.gov/pubmed/12208164", "http://www.ncbi.nlm.nih.gov/pubmed/18203126", "http://www.ncbi.nlm.nih.gov/pubmed/23154605", "http://www.ncbi.nlm.nih.gov/pubmed/21119657", "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "http://www.ncbi.nlm.nih.gov/pubmed/23623693", "http://www.ncbi.nlm.nih.gov/pubmed/23131519", "http://www.ncbi.nlm.nih.gov/pubmed/21730975", "http://www.ncbi.nlm.nih.gov/pubmed/12441204", "http://www.ncbi.nlm.nih.gov/pubmed/21445935" ], "ideal_answer": [ "Digit ratio (2D:4D) is associated with gastric cancer, prostate cancer, breast cancer, cervical intraepithelial neoplasia and oral squamous cell carcinoma. 2D:4D was found to be higher in patients diagnosed with gastric cancer and prostate cancer patients relative to controls. Among prostate cancer patients, 2D:4D shows strong differences between African-Americans and Caucasians; however, it does not correlate with disease severity in men already diagnosed with prostate cancer. However, other authors did not find an association between 2D:4D and prostate cancer risk.\n 2D:4D is not associated with testicular germ cell tumors." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "summary", "id": "54f08fa494afd61504000017", "snippets": [ { "offsetInBeginSection": 883, "offsetInEndSection": 1295, "text": "RESULTS: Right 2D:4D was not associated with TGCT [odds ratio (OR) for a one-standard deviation (SD) increase in right-hand 2D:4D: 1.12, 95% confidence interval (CI): 0.93-1.34]. The results were consistent when evaluating the association based on the left hand. The difference between right and left-hand 2D:4D was also not associated with TGCT risk [OR for a one-SD increase in \u0394R-L: 1.03, 95% CI: 0.87-1.23]. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23623693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Digit ratio (2D:4D) is associated with gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23218867", "endSection": "title" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1222, "text": "RESULTS: GCA group presented significantly higher left 2D:4D, but significantly lower R-L in comparison to healthy controls, particularly so for males. Digit ratio did not correlate to clinical staging or TNM staging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23218867", "endSection": "abstract" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1529, "text": "The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23218867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Higher second fourth digit ratio predicts higher incidence of prostate cancer in prostate biopsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154605", "endSection": "title" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1091, "text": "2D/4D ratio >0,95 (OR (CI 95%) 4,4 (1,491-13,107) was related to neoplasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154605", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1363, "text": "CONCLUSION: High digit ratio predicts PCa in men undergoing prostate biopsy. Digit ratio >0,95 has 4-fold risk of PCa compared to men with digit ratio \u22640.95.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154605", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1638, "text": "RESULTS: African-American men with prostate cancer are 3.70 times more likely to have a low 2D:4D digit ratio than Caucasian men with prostate cancer (95% confidence interval: 1.98, 6.92; P < 0.0001). There were no statistically significant differences in the presence of metastasis, Gleason score, family history or age at diagnosis by digit ratio. CONCLUSION: 2D:4D ratio shows strong differences between African-Americans and Caucasians; however, it does not correlate with disease severity in men already diagnosed with prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146972", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 1093, "text": "RESULTS: We found a direct association between left 2D:4D and breast cancer risk, an inverse association between \u0394(r-l) and risk of breast cancer, but no association between right 2D:4D and breast cancer risk. Among breast cancer cases, both right 2D:4D and \u0394(r-l) were inversely associated with age at diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "endSection": "abstract" }, { "offsetInBeginSection": 1261, "offsetInEndSection": 1372, "text": "CONCLUSION: Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 280, "text": "Recent studies have reported a strong association between 2D:4D and risk of prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21730975", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 707, "text": "RESULTS: No association was observed between 2D:4D and prostate cancer risk overall (HRs 1.00; 95% CIs, 0.92-1.08 for right, 0.93-1.08 for left). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21730975", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1066, "text": "CONCLUSION: Our results are not consistent with an association between 2D:4D and overall prostate cancer risk, but we cannot exclude a weak inverse association between 2D:4D and early onset prostate cancer risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21730975", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1295, "text": "Males in the OSCC group presented significantly higher digit ratio (P = 0.03) in comparison with males with OPLs and individuals without oral lesions. CONCLUSIONS: According to the results, males with the higher digit ratio seem to be more prone to undergo malignization of lesions in the oral cavity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21445935", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 774, "text": "Compared with index finger shorter than ring finger (low 2D\u2009:\u20094D), men with index finger longer than ring finger (high 2D\u2009:\u20094D) showed a negative association, suggesting a protective effect with a 33% risk reduction (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.57-0.80). Risk reduction was even greater (87%) in age group <60 (OR 0.13, 95% CI 0.09-0.21). CONCLUSION: Pattern of finger lengths may be a simple marker of prostate cancer risk, with length of 2D greater than 4D suggestive of lower risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21119657", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1284, "text": "In the case-control analysis (n = 263), after controlling for ethnicity, women who developed CIN were significantly more likely to have a higher 2D:4D compared with HPV-negative women. A similar, nonsignificant trend was observed among women with a persistent HPV infection. CONCLUSION: Lower fetal androgen exposure may predispose to persistent HPV and increased risk of CIN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18203126", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 448, "text": "Low numbers of CAG repeats and low 2D:4D are both associated with high sperm numbers and protection against breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12208164", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1320, "text": "Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "endSection": "abstract" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1478, "text": "A lower digit ratio is related to an increased detection rate of prostate cancer, a high percentage of core cancer volume and a high Gleason score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23131519", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 311, "text": " Digit ratio could act as a possible marker for cancer predisposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23218867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Right hand digit ratio (2D:4D) is associated with oral cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21445935", "endSection": "title" }, { "offsetInBeginSection": 1260, "offsetInEndSection": 1371, "text": "CONCLUSION: Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Second to fourth digit ratio: a predictor of prostate-specific antigen level and the presence of prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20633006", "endSection": "title" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1375, "text": "CONCLUSIONS: Patients with a lower digit ratio have higher risks of prostate biopsy and prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20633006", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 890, "text": "Second and fourth digit ratio has also found to be correlated with sexual orientation, left hand preference autism and some adult onset diseases such as breast cancer and myocardial infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12441204", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 447, "text": "Low numbers of CAG repeats and low 2D:4D are both associated with high sperm numbers and protection against breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12208164", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 876, "text": "Findings from AR studies predict that low 2D:4D will be associated with prostate and hepatocellular cancer, urolithiasis, ADHD, ankylosing spondylitis, spontaneous abortion, and polycystic ovaries, while high 2D:4D will be associated with motor neuron diseases and endometrial cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12208164", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 960, "text": "We found a direct association between left 2D:4D and breast cancer risk, an inverse association between \u0394(r-l) and risk of breast cancer, but no association between right 2D:4D and breast cancer risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "endSection": "abstract" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1332, "text": "Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1483, "text": "The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23218867", "endSection": "abstract" } ] }, { "body": "Is TREM2 associated with Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23855982", "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "http://www.ncbi.nlm.nih.gov/pubmed/24041969", "http://www.ncbi.nlm.nih.gov/pubmed/23582655", "http://www.ncbi.nlm.nih.gov/pubmed/23562540", "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "http://www.ncbi.nlm.nih.gov/pubmed/17088018", "http://www.ncbi.nlm.nih.gov/pubmed/24119542", "http://www.ncbi.nlm.nih.gov/pubmed/23510020", "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "http://www.ncbi.nlm.nih.gov/pubmed/23533697", "http://www.ncbi.nlm.nih.gov/pubmed/23692967", "http://www.ncbi.nlm.nih.gov/pubmed/24002183" ], "ideal_answer": [ "A rare variant of the TREM2 gene, which encodes the triggering receptor encoded in myeloid cells 2 (rs75932628-T) causing a R47H substitution has been associated with both early and late onset Alzheimer's disease in various populations. Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons. Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients which indicates that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis. Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/TREM2_HUMAN", "http://www.uniprot.org/uniprot/TREM2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "yesno", "id": "531a31a1b166e2b806000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Absence of TREM2 polymorphisms in patients with Alzheimer's disease and Frontotemporal Lobar Degeneration", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17088018", "endSection": "title" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1210, "text": " These data demonstrate that TREM2 coding region is highly conserved, implying a crucial role of this receptor. Further studies, including a functional analysis, are certainly required to clarify the role of TREM2 in neurodegenerative processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17088018", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 278, "text": "Moreover, a rare TREM2 exon 2 variant (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an odds ratio as strong as that for APOE\u03b54", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119542", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 601, "text": "We observed an enrichment of rare variants across TREM2 in both AD and FTD patients compared to controls, most notably in the extracellular IgV-set domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119542", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 966, "text": "None of the rare variants individually reached significant association, but the frequency of p.R47H was increased ~ 3-fold in both AD and FTD patients compared to controls, in line with previous reports", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119542", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1313, "text": "Our data corroborate and extend previous findings to include an increased frequency of rare heterozygous TREM2 variations in AD and FTD, and show that TREM2 variants may play a role in neurodegenerative diseases in general.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119542", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 170, "text": "non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041969", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1076, "text": "These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041969", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 279, "text": " Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002183", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 672, "text": "Our results indicate that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002183", "endSection": "abstract" }, { "offsetInBeginSection": 7, "offsetInEndSection": 157, "text": "studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23855982", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 850, "text": "This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23855982", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 965, "text": "Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17088018", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1048, "text": "A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1517, "text": "We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "endSection": "abstract" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1835, "text": "Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 197, "text": "rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 690, "text": "These results confirm the association between this variant and AD and underline its involvement in early-onset cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 125, "text": "recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 269, "text": "Rs75932628-T is a rare nonsynonymous variant (p.R47H) that confers a high risk of AD with an effect size similar to that of the APOE \u025b4 allele", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1043, "text": "Here, we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "endSection": "abstract" }, { "offsetInBeginSection": 7, "offsetInEndSection": 285, "text": "works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E \u03b54 allele", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 636, "text": "The reduced function of TREM2 was speculated to be the main cause in the pathogenic effects of this risk variant, and TREM2 is highly expressed in white matter, as well as in the hippocampus and neocortex, which is partly consistent with the pathological features reported in AD brain, indicating the possible involvement of TREM2 in AD pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "abstract" }, { "offsetInBeginSection": 638, "offsetInEndSection": 858, "text": "Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 980, "text": "TREM2 also participates in the regulation of phagocytic pathways that are responsible for the removal of neuronal debris", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1295, "text": "Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 927, "text": "Under the hypothesis that low-prevalence variants showing moderate-to-high effect size may be associated with risk for sAD, two independent research groups have demonstrated that a rare variant (rs75932628, encoding a substitution of arginine by histidine at residue 47 (R47H), in the TREM2 gene, which encodes the triggering receptor expressed on myeloid cells 2) is significantly associated with an increased susceptibility to sAD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23510020", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 604, "text": "Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533697", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 748, "text": "TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23562540", "endSection": "abstract" }, { "offsetInBeginSection": 7, "offsetInEndSection": 131, "text": "evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582655", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1343, "text": "These data suggest that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582655", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1666, "text": "The association of TREM2 variants with AD brings innate immune signaling into the light, affirming innate immunity's role as a significant factor in AD pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692967", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1113, "text": "The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533697", "endSection": "abstract" }, { "offsetInBeginSection": 1861, "offsetInEndSection": 2125, "text": "Even though we are more at the beginning than at the end of sAD genetics, there is some reason for optimism given the recent identification of novel risk or protective variants (such as rare TREM2 and APP mutations) showing strong statistical associations with sAD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23510020", "endSection": "abstract" } ] }, { "body": "Does the protein mTOR regulate autophagy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24275666", "http://www.ncbi.nlm.nih.gov/pubmed/24209762", "http://www.ncbi.nlm.nih.gov/pubmed/23940798", "http://www.ncbi.nlm.nih.gov/pubmed/24024901", "http://www.ncbi.nlm.nih.gov/pubmed/24255881", "http://www.ncbi.nlm.nih.gov/pubmed/24326530", "http://www.ncbi.nlm.nih.gov/pubmed/24275748", "http://www.ncbi.nlm.nih.gov/pubmed/24092929", "http://www.ncbi.nlm.nih.gov/pubmed/24131573", "http://www.ncbi.nlm.nih.gov/pubmed/23982275", "http://www.ncbi.nlm.nih.gov/pubmed/24278483", "http://www.ncbi.nlm.nih.gov/pubmed/24265855" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10789460", "o": "C39159" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "mTOR Signaling Pathway" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A10789460" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "C39159" } ], "ideal_answer": [ "mammalian target of rapamycin (mTOR) is a major negative regulator of autophagy." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/MTOR_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010508", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010506", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.uniprot.org/uniprot/MTOR_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010507" ], "type": "yesno", "id": "5505ad7ff73303d458000007", "snippets": [ { "offsetInBeginSection": 614, "offsetInEndSection": 700, "text": "autophagy is negatively regulated by the mammalian target of rapamycin receptor (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24326530", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 300, "text": "Subjecting cells to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR signaling pathway triggering increased autophagic flux. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24275748", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 501, "text": "Several pathways, including mTOR, have been shown to regulate autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24278483", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1205, "text": "these results provide insights into the mechanism by which hyperactivation of mTORC1 promotes breast cancer progression through increasing autophagy and Akt activation in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24275666", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 126, "text": " the canonical mTOR-controlled autophagy pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265855", "endSection": "abstract" }, { "offsetInBeginSection": 2935, "offsetInEndSection": 3019, "text": "mTOR inhibition severely impairs liver regeneration and increases autophagy after PH", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255881", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 537, "text": "mTOR remains at a high level and inhibits autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24209762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24131573", "endSection": "title" }, { "offsetInBeginSection": 231, "offsetInEndSection": 309, "text": "mammalian target of rapamycin (mTOR), a major negative regulator of autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24131573", "endSection": "abstract" }, { "offsetInBeginSection": 1593, "offsetInEndSection": 1633, "text": "mTOR suppresses granulosa cell autophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24131573", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1275, "text": "Mammalian target of rapamycin (mTOR), a potent suppressor of autophagy,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24092929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The mTOR signaling pathway integrates inputs from a variety of upstream stimuli to regulate diverse cellular processes including proliferation, growth, survival, motility, autophagy, protein synthesis and metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24024901", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1291, "text": "The activation of mammalian target of rapamycin (mTOR) signaling pathway blocks the effects of ghrelin-induced autophagy and apoptosis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982275", "endSection": "abstract" }, { "offsetInBeginSection": 1516, "offsetInEndSection": 1580, "text": " inducing apoptosis and autophagy via the mTOR signaling pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982275", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 128, "text": " The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940798", "endSection": "abstract" } ] }, { "body": "Which are the mains risk factors of metabolic syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21448316", "http://www.ncbi.nlm.nih.gov/pubmed/24290837", "http://www.ncbi.nlm.nih.gov/pubmed/24227418", "http://www.ncbi.nlm.nih.gov/pubmed/24308220", "http://www.ncbi.nlm.nih.gov/pubmed/24320032", "http://www.ncbi.nlm.nih.gov/pubmed/24320038", "http://www.ncbi.nlm.nih.gov/pubmed/24269186", "http://www.ncbi.nlm.nih.gov/pubmed/24247648", "http://www.ncbi.nlm.nih.gov/pubmed/24277673", "http://www.ncbi.nlm.nih.gov/pubmed/24203651", "http://www.ncbi.nlm.nih.gov/pubmed/24152591", "http://www.ncbi.nlm.nih.gov/pubmed/24314947", "http://www.ncbi.nlm.nih.gov/pubmed/24287796", "http://www.ncbi.nlm.nih.gov/pubmed/24313546", "http://www.ncbi.nlm.nih.gov/pubmed/24326560", "http://www.ncbi.nlm.nih.gov/pubmed/24295929", "http://www.ncbi.nlm.nih.gov/pubmed/23093663", "http://www.ncbi.nlm.nih.gov/pubmed/18793503", "http://www.ncbi.nlm.nih.gov/pubmed/24309486", "http://www.ncbi.nlm.nih.gov/pubmed/24274871", "http://www.ncbi.nlm.nih.gov/pubmed/24327239", "http://www.ncbi.nlm.nih.gov/pubmed/18931101", "http://www.ncbi.nlm.nih.gov/pubmed/24314937", "http://www.ncbi.nlm.nih.gov/pubmed/24305580", "http://www.ncbi.nlm.nih.gov/pubmed/16855517", "http://www.ncbi.nlm.nih.gov/pubmed/24191289" ], "ideal_answer": [ "Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels. Metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes." ], "exact_answer": [ [ "Obesity" ], [ "High blood pressure", "Hypertension" ], [ "High serum triglycerides" ], [ "Low high-density cholesterol (HDL) levels" ], [ "Diabetes type 2" ], [ "Dyslipidaemia" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024821", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008659", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008660" ], "type": "list", "id": "5326c6fed6d3ac6a3400000c", "snippets": [ { "offsetInBeginSection": 20, "offsetInEndSection": 1204, "text": "tigated the association between circulating levels of 60 and 70 kDa heat-shock proteins (HSP60 and 70) and cardiovascular risk factors in postmenopausal women with or without metabolic syndrome (MetS). This cross-sectional study included 311 Brazilian women (age \u226545 years with amenorrhea \u226512 months). Women showing three or more of the following diagnostic criteria were diagnosed with MetS: waist circumference (WC) \u226588 cm, blood pressure \u2265130/85 mmHg, triglycerides \u2265150 mg/dl, high-density lipoprotein (HDL) <50 mg/dl, and glucose \u2265100 mg/dl. Clinical, anthropometric, and biochemical parameters were collected. HSP60, HSP70, antibodies to HSP60 and HSP70, and C-reactive protein (CRP) levels were measured in serum. Student's t test, Kruskal-Wallis test, chi-square test, and Pearson correlation were used for statistical analysis. Of the 311 women, 30.9 % (96/311) were diagnosed with MetS. These women were, on average, obese with abdominal fat deposition and had lower HDL values as well as higher triglycerides and glucose levels. Homeostasis model assessment-insulin resistant (HOMA-IR) test values in these women were compatible with insulin resistance (P\u2009<\u20090.05). CRP and ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24327239", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 289, "text": " is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Several", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320038", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 380, "text": "alence of the metabolic syndrome (MetS), a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder is not only associated with a higher risk of appearance of type 2 diabetes and cardiovascular events, but impacts on the liver in different ways. Nonalc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320032", "endSection": "abstract" }, { "offsetInBeginSection": 22, "offsetInEndSection": 1148, "text": "bolic syndrome (MS) components, such as dyslipidemia, prothrombotic status, and increased blood pressure, are risk factors for patients with renal disease. Visceral fat mass is closely related to the MS and atherosclerosis. We investigated the effects of body compositions and MS on anemia parameters and recombinant human erythropoietin (rHuEPO) requirements in maintenance hemodialysis patients. METHODS: Body composition (body mass index and bioimpedance analysis) and laboratory data were obtained from 110 dialysis patients. The MS was identified according to ATP-III criteria. Anemia parameters, hemoglobin (Hgb), albumin, C-reactive protein (CRP), calcium, phosphorus, parathormone levels, and rHuEPO requirements over the last 6 months were retrospectively analyzed. RESULTS: Patients with the MS seem to reach target Hgb levels more frequently (10-12 g/dL; 66.3% vs 84.8%; P = .03) without any difference in total intravenous iron therapy dosage. MS patients also required lower rHuEPO for reaching similar Hgb levels compared with patients without MS (2679.3 \u00b1 1936.1 vs 3702.5 \u00b1 2213.0 U/kg/6 mo; P = .02). There we", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24314937", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 1871, "text": "bolic syndrome (MetS) is typically diagnosed based on abnormalities in specific clustered clinical measures that are associated with increased risk for coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM). However, current MetS criteria result in racial/ethnic discrepancies. Our goals were to use confirmatory factor analysis (CFA) to delineate differential contributions to MetS by sub-group, and if contributions were discovered, develop sex and racial/ethnic-specific equations to calculate MetS severity. RESEARCH DESIGN AND METHODS: Using data on adults from the National Health and Nutrition Examination Survey 1999-2010, we performed a CFA of a single MetS factor that allowed differential loadings across groups, resulting in a sex and race/ethnicity-specific continuous MetS severity score. RESULTS: Loadings to the single MetS factor differed by sub-group for each MetS component (p<0.001), with lower factor loadings among non-Hispanic-blacks for triglycerides and among Hispanics for waist circumference. Systolic blood pressure exhibited low factor loadings among all groups. MetS severity scores were correlated with biomarkers of future disease (high-sensitivity C-reactive-protein, uric acid, insulin resistance). Non-Hispanic-black-males with diabetics had a low prevalence of MetS but high MetS severity scores that were not significantly different from other racial/ethnic groups. CONCLUSIONS: This analysis among adults uniquely demonstrated differences between sexes and racial/ethnic groups regarding contributions of traditional MetS components to an assumed single factor. The resulting equations provide a clinically-accessible and interpretable continuous measure of MetS for potential use in identifying adults at higher risk for MetS-related diseases and following changes within individuals over time. These eq", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24290837", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 305, "text": " study, we aim to examine the associations of obesity related loci with risk of metabolic syndrome (MetS) in a children population from China. A tota", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24269186", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 199, "text": "alence of obesity is on the increase, and consequently metabolic syndrome is also becoming a serious health problem in children and adolescents all over the world. This rev", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247648", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 333, "text": "ciation between alopecia areata (AA), psoriasis, and other autoimmune diseases has been well reported in the literature, an association with metabolic syndrome has not been reported. We present two young women with the combination of severe psoriasis, androgen excess, metabolic syndrome, thyroiditis, and AA. Both w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24326560", "endSection": "abstract" } ] }, { "body": "Which multiple kinase inhibitors are used in cancer therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16159418" ], "ideal_answer": [ "Multiple kinase inhibitors used in cancer therapy include ZD6474, SU11248, AEE 788, sorafenib, vatalanib, and AG-013736." ], "exact_answer": [ [ "ZD6474" ], [ "SU11248" ], [ "AEE 788" ], [ "sorafenib" ], [ "vatalanib" ], [ "AG-013736" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004358", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033673", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011494", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047428", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "list", "id": "5319a6c9b166e2b806000022", "snippets": [ { "offsetInBeginSection": 660, "offsetInEndSection": 973, "text": "These inhibitors generally hinder the phosphorylation of several protein kinases of membrane receptors, such as vascular endothelial growth factor receptors, platelet-derived growth factor receptors, the human epidermal growth factor receptor family, and cytoplasmic receptors such as c-Kit, Raf kinase, and FLT3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16159418", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1061, "text": "These inhibitors include ZD6474, SU11248, AEE 788, sorafenib, vatalanib, and AG-013736.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16159418", "endSection": "abstract" } ] }, { "body": "Has proteomics been used in the study of Pick's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11880199", "http://www.ncbi.nlm.nih.gov/pubmed/16987245", "http://www.ncbi.nlm.nih.gov/pubmed/16555340", "http://www.ncbi.nlm.nih.gov/pubmed/12650976" ], "ideal_answer": [ "Yes, proteomics has been used in the study of Pick's disease." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057180", "http://www.disease-ontology.org/api/metadata/DOID:11870", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020774" ], "type": "yesno", "id": "532f05bdd6d3ac6a34000026", "snippets": [ { "offsetInBeginSection": 776, "offsetInEndSection": 993, "text": "In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16987245", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 529, "text": "Thus, brain and cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease, Down syndrome, Pick's disease, Parkinson's disease, schizophrenia, and other disorders as well as brain and CSF from animals serving as models of neurological disorders have been analyzed by proteomics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16555340", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 771, "text": "The present study is designed to investigate expression of peroxiredoxins (Prxs), the newly characterized family of highly conserved antioxidant enzymes, and other antioxidant enzymes in frontal cortex and cerebellum of DS, AD and PD patients using the technique of proteomics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12650976", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 486, "text": "HMT levels were measured in the frontal cortex and cerebellum of brains of patients with AD, DS, and PiD, and normal aged subjects using proteomics techniques. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11880199", "endSection": "abstract" } ] }, { "body": "Are there any urine biomarkers for bladder cancer diagnosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24139504", "http://www.ncbi.nlm.nih.gov/pubmed/24578952", "http://www.ncbi.nlm.nih.gov/pubmed/22559832", "http://www.ncbi.nlm.nih.gov/pubmed/24183881", "http://www.ncbi.nlm.nih.gov/pubmed/18070176", "http://www.ncbi.nlm.nih.gov/pubmed/24306957", "http://www.ncbi.nlm.nih.gov/pubmed/18923359", "http://www.ncbi.nlm.nih.gov/pubmed/24140246", "http://www.ncbi.nlm.nih.gov/pubmed/19181545", "http://www.ncbi.nlm.nih.gov/pubmed/22426337", "http://www.ncbi.nlm.nih.gov/pubmed/22615872", "http://www.ncbi.nlm.nih.gov/pubmed/22888342", "http://www.ncbi.nlm.nih.gov/pubmed/20960509", "http://www.ncbi.nlm.nih.gov/pubmed/23764080", "http://www.ncbi.nlm.nih.gov/pubmed/19565266", "http://www.ncbi.nlm.nih.gov/pubmed/23094052", "http://www.ncbi.nlm.nih.gov/pubmed/20082749", "http://www.ncbi.nlm.nih.gov/pubmed/24212086", "http://www.ncbi.nlm.nih.gov/pubmed/22792272", "http://www.ncbi.nlm.nih.gov/pubmed/23945108", "http://www.ncbi.nlm.nih.gov/pubmed/20657287", "http://www.ncbi.nlm.nih.gov/pubmed/24281040", "http://www.ncbi.nlm.nih.gov/pubmed/15341676", "http://www.ncbi.nlm.nih.gov/pubmed/23300915" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7638941", "o": "C16181" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7638941", "o": "Cancer Biomarkers Research Group" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1516166", "o": "http://linkedlifedata.com/resource/umls/label/A7638941" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7638941", "o": "NCI Thesaurus" } ], "ideal_answer": [ "Bladder cancer is any of several types of malignancy arising from the epithelial lining of the urinary bladder. Rarely the bladder is involved by non-epithelial cancers, such as lymphoma or sarcoma. It is a disease in which abnormal cells multiply without control in the bladder.The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer recapitulates the normal histology of the urothelium and is known as transitional cell carcinoma or more properly urothelial cell carcinoma. It is estimated that there are 383,000 cases of bladder cancer worldwide", "Yes, there are. Urine biomarkers for bladder cancer diagnosis range from voided urine cytology and the UroVysion\u00ae cytogenetic test, to fluorescence in situ hybridisation (FISH), ImmunoCyt, NMP22, Bladder Tumor Antigen, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, Survivin, telomerase, IL-8, MMP-9 and 10, PAI-1, VEGF, ANG, CA9 and APOE." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001749", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014554", "http://www.disease-ontology.org/api/metadata/DOID:6933", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014556", "http://www.disease-ontology.org/api/metadata/DOID:4007", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001743", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055088", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054316", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042241", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.uniprot.org/uniprot/BLCAP_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:11054" ], "type": "yesno", "id": "52cb9b9b03868f1b0600002d", "snippets": [ { "offsetInBeginSection": 1232, "offsetInEndSection": 1517, "text": "CONCLUSIONS: Several gene-based urinary biomarkers have demonstrated promise in initial studies, which now need to be rigorously validated in the clinical setting for them to be translated into clinically useful tests in diagnosis, surveillance or risk-stratification of bladder cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140246", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1865, "text": " Novel promising markers are in various stages of clinical testing, and a panel of biomarkers may serve in the future as a feasible alternative to urine cytology and cystoscopy for the screening, detection, and follow-up of non-muscle invasive bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15341676", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1130, "text": "RESULTS: Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer. The 7 biomarkers were assessed in a new model, which had an AUROC of 0.88 (95% CI 0.84-0.93), and 74% sensitivity and 90% specificity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23764080", "endSection": "abstract" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1644, "text": "The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23764080", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 1417, "text": "The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23094052", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 401, "text": ": Histopathological grading of papillary urothelial tumors (PUTs) of the urinary bladder is subjective and poorly reproducible. We investigated the relationship between the expression of frequently deregulated microRNAs (miRNAs) as well as their target genes (ZEB1/ZEB2) and bladder cancer histopathological grade in an attempt to find a miRNA that might allow more reliable grading of PUTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24306957", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1914, "text": "The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22792272", "endSection": "abstract" }, { "offsetInBeginSection": 1738, "offsetInEndSection": 1959, "text": "HYAL-1 and HAS1 expression predicted BCa metastasis, and HYAL-1 expression also predicted disease-specific survival. Furthermore, the combined HAS2-HYAL-1 biomarker detected BCa and significantly predicted its recurrence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20960509", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 124, "text": "Cancer biomarkers are the backbone for the implementation of individualized approaches to bladder cancer (BCa). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20960509", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 676, "text": "Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8), Matrix metallopeptidase 9 (MMP-9) and Syndecan in the diagnosis of BCa through urinalysis. METHODS: Voided urines from 127 subjects, cancer subjects (n = 64), non-cancer subjects (n = 63) were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22559832", "endSection": "abstract" }, { "offsetInBeginSection": 1653, "offsetInEndSection": 1998, "text": ". There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients. Collectively, our findings identify caveats intrinsic to the common practice of protein standardization in biomarker discovery studies conducted on urine, particularly in patients with hematuria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300915", "endSection": "abstract" } ] }, { "body": "List types of avoided words in bacterial genomes", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12762852", "http://www.ncbi.nlm.nih.gov/pubmed/9171096" ], "ideal_answer": [ "Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a statistically significant level in the genomes of several bacteria, including the completely sequenced Haemophilus influenzae and Synechocystis sp. genomes and in the complete genome of the archaeon Methanococcus jannaschii. Palindromes corresponding to sites for restriction enzymes from other species are also avoided, albeit less significantly, suggesting that in the course of evolution bacterial DNA has been exposed to a wide spectrum of restriction enzymes, probably as the result of lateral transfer mediated by mobile genetic elements, such as plasmids and prophages. Palindromic words appear to accumulate in DNA once it becomes isolated from restriction-modification systems, as demonstrated by the case of organellar genomes." ], "exact_answer": [ [ "Short palindromic sequences (4, 5 and 6 bp palindromes)" ], [ "Palindromes corresponding to sites for restriction enzymes from other species" ] ], "type": "list", "id": "56a37e33496b62f23f000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Avoidance of palindromic words in bacterial and archaeal genomes: a close connection with restriction enzymes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9171096", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a statistically significant level in the genomes of several bacteria, including the completely sequenced Haemophilus influenzae and Synechocystis sp. genomes and in the complete genome of the archaeon Methanococcus jannaschii.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9171096", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 1154, "text": "Palindromes corresponding to sites for restriction enzymes from other species are also avoided, albeit less significantly, suggesting that in the course of evolution bacterial DNA has been exposed to a wide spectrum of restriction enzymes, probably as the result of lateral transfer mediated by mobile genetic elements, such as plasmids and prophages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9171096", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1315, "text": "Palindromic words appear to accumulate in DNA once it becomes isolated from restriction-modification systems, as demonstrated by the case of organellar genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9171096", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1642, "text": "In certain cases, a comparison of avoided palindromic words in taxonomically related bacteria shows a pattern of relatedness of their R-M systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12762852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Recognition sites for type II restriction and modification enzymes in genomes of several bacteria are recognized as semi-palindromic motifs and are avoided at a significant degree.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12762852", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1506, "text": "On the basis of the set of most avoided words, and in accordance to the IUPAC coding standards, suggestions are made regarding potential recognition sequences. In certain cases, a comparison of avoided palindromic words in taxonomically related bacteria shows a pattern of relatedness of their R-M systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12762852", "endSection": "abstract" } ] }, { "body": "Which gene(s) should be genotyped in order to prescribe the drug Cetuximab (anti-EGFR)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20645028", "http://www.ncbi.nlm.nih.gov/pubmed/20637356", "http://www.ncbi.nlm.nih.gov/pubmed/19367287", "http://www.ncbi.nlm.nih.gov/pubmed/24152305", "http://www.ncbi.nlm.nih.gov/pubmed/21673069", "http://www.ncbi.nlm.nih.gov/pubmed/19368524", "http://www.ncbi.nlm.nih.gov/pubmed/21036743", "http://www.ncbi.nlm.nih.gov/pubmed/23671647", "http://www.ncbi.nlm.nih.gov/pubmed/18810446", "http://www.ncbi.nlm.nih.gov/pubmed/20619739", "http://www.ncbi.nlm.nih.gov/pubmed/22287728", "http://www.ncbi.nlm.nih.gov/pubmed/21851273", "http://www.ncbi.nlm.nih.gov/pubmed/19343364", "http://www.ncbi.nlm.nih.gov/pubmed/21686179", "http://www.ncbi.nlm.nih.gov/pubmed/23299277", "http://www.ncbi.nlm.nih.gov/pubmed/22735045" ], "ideal_answer": [ "KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients.\nOther genes are such as EGFR, BRAF and T53 have also been suggested to be genotyped in order to evaluate the drug responsivness." ], "exact_answer": [ [ "KRAS" ], [ "EGFR" ], [ "BRAF" ], [ "T53" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005838", "http://www.biosemantics.org/jochem#4002122" ], "type": "list", "id": "5518414a15fa47643f000001", "snippets": [ { "offsetInBeginSection": 222, "offsetInEndSection": 473, "text": "Treatment of metastatic colorectal cancer with targeted anti-EGFR therapeutics such as cetuximab extends survival in only 25% of patients who test wild-type for KRAS, while the majority of patients prove resistant (J Clin Oncol 28(7):1254-1261, 2010).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152305", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 973, "text": ". Somatic mutation of the EGFR signalling pathway is a prevalent mechanism of resistance to cetuximab (Nature 486(7404):532-536, 2012). If the human genome harbours variants that influence susceptibility of the EGFR pathway to oncogenic mutation, such variants could also be prognostic for cetuximab responsiveness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152305", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 271, "text": "KRAS mutations are strong predictors for clinical outcomes of EGFR-targeted treatments such as cetuximab and panitumumab in metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23671647", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 176, "text": "KRAS mutation is widely accepted as a strong, negative predictive marker for anti-epidermal growth factor receptor antibodies, including cetuximab and panitumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23299277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-Epidermal Growth Factor Receptor (EGFR) antibodies, such as cetuximab or panitumumab. KRAS mutations are unambiguously linked to a lack of response to these targeted therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735045", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1335, "text": "The EGFR-R497K polymorphism is a potential predictor for overall survival in HNSCC patients treated with cetuximab based therapy in the palliative setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Laboratories are increasingly required to perform molecular tests for the detection of mutations in the KRAS gene in metastatic colorectal cancers to allow better clinical management and more effective treatment for these patients. KRAS mutation status predicts a patient's likely response to the monoclonal antibody cetuximab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21851273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21686179", "endSection": "abstract" }, { "offsetInBeginSection": 1637, "offsetInEndSection": 1848, "text": " This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21673069", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 1076, "text": "Intratumoral gene expression levels of EGFR, VEGFR2 and NRP as well as polymorphisms in FCGR3A, CyclinD1 and EGFR could predict clinical outcome in mCRC patients enrolled in BOND2, independent of KRAS mutation status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21036743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 624, "text": "Numerous clinical studies have shown that anti-EGFR therapies are effective only in a subset of patients with colorectal cancer. Even though mutations in the KRAS gene have been confirmed as negative predictors of the response to EGFR-targeted therapies, not all KRAS wild-type (wt-KRAS) patients will respond to treatment. Recent studies have demonstrated that additionally wild-type BRAF (wt-BRAF) genotype is required for response to panitumumab or cetuximab, suggesting that BRAF genotype criteria should be used together with KRAS genotype for selecting the patients who are about to benefit from the anti-EGFR therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20645028", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1366, "text": "KRAS mutation is a dramatic example of single nucleotide polymorphism, which is able to identify a priori patients that could receive or not an anti-EGFR monoclonal antibody such as cetuximab or panitumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20637356", "endSection": "abstract" }, { "offsetInBeginSection": 3095, "offsetInEndSection": 3286, "text": "While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20619739", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 253, "text": "Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19368524", "endSection": "abstract" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1328, "text": ". This study suggests that TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetuximab-based CT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19367287", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1358, "text": "A KRAS mutation confers resistance to cetuximab, which reduces treatment options, especially in first-line. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19343364", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1032, "text": "KRAS genotyping was recently introduced as predictive biomarker, since only tumors carrying a wildtype were found to respond to treatment with panitumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18810446", "endSection": "abstract" } ] }, { "body": "Is signal transducer and activator of transcription-3 (STAT3) critical for tumor angiogenesis progression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24042330", "http://www.ncbi.nlm.nih.gov/pubmed/20204067", "http://www.ncbi.nlm.nih.gov/pubmed/24305878", "http://www.ncbi.nlm.nih.gov/pubmed/24058783", "http://www.ncbi.nlm.nih.gov/pubmed/24200081", "http://www.ncbi.nlm.nih.gov/pubmed/22076197", "http://www.ncbi.nlm.nih.gov/pubmed/24307888", "http://www.ncbi.nlm.nih.gov/pubmed/17610223", 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"p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1514955", "o": "http://linkedlifedata.com/resource/umls/label/A10788344" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1514955", "o": "http://linkedlifedata.com/resource/umls/label/A10788344" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10788344", "o": "Stat3 Signaling Pathway" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1514955", "o": "http://linkedlifedata.com/resource/umls/label/A7663266" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7663266", "o": "C39238" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/Q7Z4H9", "o": "http://purl.uniprot.org/citations/12853948" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/12853948", "o": "Nature" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51375A34483900F", "o": "STAT3-interacting protein as a repressor" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/12853948", "o": "http://purl.uniprot.org/pubmed/12853948" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/12853948", "o": "http://purl.uniprot.org/medline/22737999" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q7Z4H9", "o": "http://linkedlifedata.com/resource/#_51375A34483900F" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInCellLine", "s": "http://purl.uniprot.org/uniprot/Q3ZN08", "o": "http://purl.uniprot.org/tissues/597" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q3ZN08", "o": "http://linkedlifedata.com/resource/#_51335A4E30380015" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Breast tumor" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Mammary tumour" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q3ZN08", "o": "http://linkedlifedata.com/resource/#_51335A4E30380014" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51335A4E30380014", "o": "STAT3-interacting protein as a repressor" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51335A4E30380015", "o": "Acrosomal protein ACPIN1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Mammary tumor" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Mammary gland tumor" } ], "ideal_answer": [ "(STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/STAT3_MOUSE", "http://www.biosemantics.org/jochem#4243664", "http://www.uniprot.org/uniprot/STAT3_BOVIN", "http://www.uniprot.org/uniprot/STAT3_CHICK", "http://www.uniprot.org/uniprot/STAT3_HUMAN", "http://www.uniprot.org/uniprot/STAT3_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043925", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045766", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045765", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050796", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001525", "http://www.uniprot.org/uniprot/STAT3_PIG", "http://www.uniprot.org/uniprot/STATC_DICDI", "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "yesno", "id": "533d0f44c45e13371400000e", "snippets": [ { "offsetInBeginSection": 50, "offsetInEndSection": 345, "text": " (STAT3) is critical for cancer progression by regulating tumor cell survival, proliferation, and angiogenesis. Herein, we investigated the regulation of STAT3 activation and the therapeutic effects of Icaritin, a prenyl flavonoid derivative from Epimedium Genus, in renal cell carcinoma (RCC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324713", "endSection": "abstract" }, { "offsetInBeginSection": 1205, "offsetInEndSection": 1377, "text": " Overall, these results suggest that Icaritin strongly inhibits STAT3 activation and is a potentially effective therapeutic option for the treatment of renal cell carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324713", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 664, "text": "we have reviewed important signaling pathways that are closely related to radiosensitization, such as cell cycle arrest, tumor angiogenesis, JAK/STAT3 signaling pathway and Mismatch repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24307888", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 270, "text": "Interleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial-mesenchymal transition (EMT) and angiogenesis are key processes in carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24274066", "endSection": "abstract" }, { "offsetInBeginSection": 1813, "offsetInEndSection": 1909, "text": "The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24274066", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 254, "text": "STAT3 plays a vital role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment and is reported to be a critical mediator of the oncogenic effects of EGFR mutations. STAT3 activation is mediated through JAK family kinases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24238495", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 2061, "text": " EESB treatment could significantly suppress the activation of several CRC-related pathways, including STAT3, Erk, and p38 signalings in tumor tissues, and alter the expression of multiple critical target genes such as Bcl-2, Bax, Cyclin D1, CDK4, and p21. These molecular effects lead to the induction of cancer cell apoptosis and inhibition of cell proliferation. Our findings demonstrate that SB possesses a broad range of antitumor activities because of its ability to affect multiple intracellular targets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231788", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1554, "text": "Western immunoblotting analyses of mouse lung tissues indicated significantly lower level of pSTAT3 and Mcl-1 in the carcinogen plus DMAPT group relative to the group treated with the carcinogen only. Given the evidence that STAT3 is activated in more than half of lung cancers and it regulates genes involved in cell proliferation, survival and angiogenesis, DMAPT is a promising agent for lung cancer chemoprevention in subjects who are at high risk of developing this devastating disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24200081", "endSection": "abstract" }, { "offsetInBeginSection": 51, "offsetInEndSection": 702, "text": "(STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24199193", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 251, "text": "STAT3) signaling pathway plays important roles in oncogenesis, angiogenesis, immunity, and tumor cell invasion. In the present study, we investigated the association of interleukin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24116074", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 585, "text": " Phosphorylated STAT3 (pSTAT3) regulates many genes that are necessarily expressed in cancer initiation, development, and progression, being involved in proliferation, anti-apoptosis, invasion, angiogenesis, and immune surveillance evasion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24005169", "endSection": "abstract" } ] }, { "body": "Which is the physiological target for LeuRS translational quality control?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24935946" ], "ideal_answer": [ "QUALITY CONTROL", "The physiological target for LeuRS translational quality control is norvaline.", "The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid selectivity is compromised, fidelity can be ensured by an inherent AARS editing activity that hydrolyses mischarged tRNAs. Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline." ], "exact_answer": [ "Norvaline" ], "concepts": [ "http://www.uniprot.org/uniprot/SYL_SHEWM", "http://www.uniprot.org/uniprot/SYL_SHESR", "http://www.uniprot.org/uniprot/SYL_COXBR", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007935", "http://www.uniprot.org/uniprot/SYL_SHESW", "http://www.uniprot.org/uniprot/SYLC_MOUSE", "http://www.uniprot.org/uniprot/SYL_SHIB3", "http://www.uniprot.org/uniprot/SYLB_AQUAE", "http://www.uniprot.org/uniprot/SYL2_METS5", "http://www.uniprot.org/uniprot/SYL_SHESA", "http://www.uniprot.org/uniprot/SYL_RICPU", "http://www.uniprot.org/uniprot/SYLC_ENCCU", "http://www.uniprot.org/uniprot/SYLC_SCHPO", "http://www.uniprot.org/uniprot/SYL_SHIBS", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011786" ], "type": "factoid", "id": "56ae57350a360a5e4500000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The physiological target for LeuRS translational quality control is norvaline.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24935946", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The physiological target for LeuRS translational quality control is norvaline", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24935946", "endSection": "title" }, { "offsetInBeginSection": 435, "offsetInEndSection": 618, "text": "Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24935946", "endSection": "abstract" } ] }, { "body": "Is sumoylation implicated in myogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16973431", "http://www.ncbi.nlm.nih.gov/pubmed/24344126", "http://www.ncbi.nlm.nih.gov/pubmed/23247248", "http://www.ncbi.nlm.nih.gov/pubmed/25002400", "http://www.ncbi.nlm.nih.gov/pubmed/16631162", "http://www.ncbi.nlm.nih.gov/pubmed/17202138", "http://www.ncbi.nlm.nih.gov/pubmed/16478538", "http://www.ncbi.nlm.nih.gov/pubmed/23637228", "http://www.ncbi.nlm.nih.gov/pubmed/16966324", "http://www.ncbi.nlm.nih.gov/pubmed/23754700" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18469770", "o": "D058207" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7814146", "o": "D024510" } ], "ideal_answer": [ "Yes, sumoylation is implicated in myogenesis.", "Yes, protein sumoylation present in myoblasts is regulated in myogenesis." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024510", "http://amigo.geneontology.org/amigo/term/GO:0016925", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058207" ], "type": "yesno", "id": "56cca4da5795f9a73e000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) has broad de-SUMOylation activities in vitro, which is essential for embryonic heart development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24344126", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 622, "text": "Silencing SENP2 can reduce myostatin expression and, therefore, promote myogenesis of skeletal muscle. These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24344126", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 426, "text": "Overexpression of c-Ski/SnoN also induces skeletal muscle differentiation, but how c-Ski/SnoN function in myogenesis is largely unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17202138", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1293, "text": "Notably, loss of sumoylation in the Lys-50 site (via a Lys-to-Arg point mutation) potently activates muscle-specific gene expression and enhances myotube formation. Our study suggests a novel role for SUMO modification in the regulation of myogenic differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17202138", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1415, "text": "Although this modification has little effect on SnoN repression of the plasminogen activator inhibitor-1 promoter and only modestly potentiates SnoN repression of the p21 promoter, SnoN sumoylation robustly augments the ability of SnoN to suppress transcription of the myogenesis master regulatory gene myogenin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16966324", "endSection": "abstract" }, { "offsetInBeginSection": 1724, "offsetInEndSection": 1861, "text": "Our study also points to a physiological role for SnoN sumoylation in the control of myogenin expression in differentiating muscle cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16966324", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 714, "text": "Here, we biochemically characterize SnoN sumoylation in detail and report the physiological function of the modification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17202138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "An essential role of small ubiquitin-like modifier (SUMO)-specific Protease 2 in myostatin expression and myogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24344126", "endSection": "title" }, { "offsetInBeginSection": 516, "offsetInEndSection": 622, "text": "These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24344126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The E3 SUMO ligase Nse2 regulates sumoylation and nuclear-to-cytoplasmic translocation of skNAC-Smyd1 in myogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25002400", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Sumoylation of the basic helix-loop-helix transcription factor sharp-1 regulates recruitment of the histone methyltransferase G9a and function in myogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23637228", "endSection": "title" }, { "offsetInBeginSection": 516, "offsetInEndSection": 637, "text": " We show that the overall load of sumoylated proteins present in myoblasts diminishes progressively throughout myogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16631162", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1059, "text": "These novel results suggest that protein sumoylation plays a pivotal role in myoblast differentiation and is required to regulate the activity of key targets downstream of MyoD and myogenin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16631162", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 435, "text": "a composite sequence motif has recently been identified that couples phosphorylation, sumoylation, and perhaps also deacetylation to control transcriptional repression in stress response, mitogen and nuclear hormone signaling, myogenesis, and neuronal differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973431", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 904, "text": "Mutation of these SUMO acceptor sites in Sharp-1 does not impact its subcellular localization but attenuates its ability to act as a transcriptional repressor and inhibit myogenic differentiation. Consistently, co-expression of the SUMO protease SENP1 with wild type Sharp-1 abrogates Sharp-1-dependent inhibition of myogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23637228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Transforming growth factor-beta-independent regulation of myogenesis by SnoN sumoylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17202138", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Ubiquitin Specific Protease 25 (USP25), a member of the deubiquitinase family, is involved in several disease-related signal pathways including myogenesis, immunity and protein degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754700", "endSection": "abstract" }, { "offsetInBeginSection": 918, "offsetInEndSection": 1317, "text": " In addition, we show that the skNAC interaction partner Smyd1 contains a putative sumoylation motif and is sumoylated in muscle cells, with depletion of Mms21/Nse2 leading to reduced concentrations of sumoylated Smyd1. Taken together, our data suggest that the function, specifically the balance between the nuclear and cytosolic roles, of the skNAC-Smyd1 complex might be regulated by sumoylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25002400", "endSection": "abstract" } ] }, { "body": "What do studies show about the effect of Induced hypothermia in premature babies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20470651", "http://www.ncbi.nlm.nih.gov/pubmed/20100756", "http://www.ncbi.nlm.nih.gov/pubmed/22320395", "http://www.ncbi.nlm.nih.gov/pubmed/19020525" ], "ideal_answer": [ "Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities in term or late preterm infants. It remains unclear to what degree preterm infants were included in these studies.\nA prospective non-randomised pilot study reported that mild hypothermia for 48 hours in preterm neonates with severe NEC (necrotising enterocolitis) seems both feasible and safe." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007036", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047928", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007234", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007235", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007752" ], "type": "summary", "id": "515dc066298dcd4e5100001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Therapeutic hypothermia is a recognized treatment for term infants with hypoxic-ischemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities. Little is known about applications of this treatment to preterm newborns.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22320395", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 179, "text": "Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in term or late preterm infants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20470651", "endSection": "sections.0" }, { "offsetInBeginSection": 263, "offsetInEndSection": 679, "text": "We aimed to establish the feasibility and safety of mild hypothermia in preterm neonates with NEC and MODS as a prelude to a randomized trial. METHODS: This was a prospective, nonrandomized pilot study of 15 preterm infants who were referred for surgical intervention of advanced NEC and failure of at least 3 organs. Whole-body cooling was achieved by ambient temperature adjustment with or without cooling mattress", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100756", "endSection": "sections.0" }, { "offsetInBeginSection": 1915, "offsetInEndSection": 2117, "text": "Mild hypothermia for 48 hours in preterm neonates with severe NEC seems both feasible and safe. Additional investigation of the efficacy of this therapeutic intervention in this population is warranted.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100756", "endSection": "sections.0" } ] }, { "body": "Describe what is the advantage of using a stain free protein gel in a Western Blot experiment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23085117", "http://www.ncbi.nlm.nih.gov/pubmed/23712695", "http://www.ncbi.nlm.nih.gov/pubmed/24429481" ], "ideal_answer": [ "Stain-Free technology can be used as a normalization tool in Western blot analysis." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015153", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013194", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005782" ], "type": "summary", "id": "54da21bf4b1fd0d33c00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "V3 stain-free workflow for a practical, convenient, and reliable total protein loading control in western blotting.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24429481", "endSection": "title" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1199, "text": "The V3 stain-free workflow makes the western blot process faster, transparent, more quantitative\u00a0and reliable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24429481", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 430, "text": "Direct Blue 71 (DB71) staining-a novel, sensitive, dye-binding staining method compatible with immunodetection-may offer advantages over these traditional loading control methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23712695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Direct Blue 71 staining as a destaining-free alternative loading control method for Western blotting.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23712695", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Stain-Free technology as a normalization tool in Western blot analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085117", "endSection": "title" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1162, "text": "Stain-Free technology appears to be more reliable, more robust, and more sensitive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085117", "endSection": "abstract" }, { "offsetInBeginSection": 1252, "offsetInEndSection": 1442, "text": "tain-Free technology offers the additional advantages of providing checkpoints throughout the Western blotting process by allowing rapid visualization of gel separation and protein transfer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085117", "endSection": "abstract" } ] }, { "body": "Which is the target of the drug Denosumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26504466", "http://www.ncbi.nlm.nih.gov/pubmed/26203221", "http://www.ncbi.nlm.nih.gov/pubmed/26508890", "http://www.ncbi.nlm.nih.gov/pubmed/26029270" ], "ideal_answer": [ "Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-\u03baB ligand (RANKL)." ], "exact_answer": [ "receptor activator of nuclear factor-\u03baB ligand", "RANKL" ], "type": "factoid", "id": "56e6ec49edfc094c1f000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Denosumab is a human monoclonal antibody which specifically blocks receptor activator of nuclear factor \u03baB ligand and is a very potent antiresorptive drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029270", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 606, "text": "denosumab, a monoclonal antibody against RANKL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26203221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Denosumab is a human monoclonal antibody indicated for the treatment of osteoporosis in postmenopausal women with a high risk of fractures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26504466", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 776, "text": "Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-\u03baB ligand (RANKL), which, through the prevention of the RANKL/RANK interaction, inhibits osteoclast-mediated bone resorption and significantly reduces the risk of vertebral, nonvertebral, and hip fractures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508890", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by a drug fostamatinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20716772", "http://www.ncbi.nlm.nih.gov/pubmed/23233565", "http://www.ncbi.nlm.nih.gov/pubmed/21211067", "http://www.ncbi.nlm.nih.gov/pubmed/20879879", "http://www.ncbi.nlm.nih.gov/pubmed/22374444", "http://www.ncbi.nlm.nih.gov/pubmed/21239804", "http://www.ncbi.nlm.nih.gov/pubmed/23151054", "http://www.ncbi.nlm.nih.gov/pubmed/23378467", "http://www.ncbi.nlm.nih.gov/pubmed/21394647", "http://www.ncbi.nlm.nih.gov/pubmed/22362000", "http://www.ncbi.nlm.nih.gov/pubmed/23055694", "http://www.ncbi.nlm.nih.gov/pubmed/22421457", "http://www.ncbi.nlm.nih.gov/pubmed/21700926", "http://www.ncbi.nlm.nih.gov/pubmed/21438742", "http://www.ncbi.nlm.nih.gov/pubmed/21209239", "http://www.ncbi.nlm.nih.gov/pubmed/22492694", "http://www.ncbi.nlm.nih.gov/pubmed/20601600", "http://www.ncbi.nlm.nih.gov/pubmed/22301676", "http://www.ncbi.nlm.nih.gov/pubmed/23078058", "http://www.ncbi.nlm.nih.gov/pubmed/20522642", "http://www.ncbi.nlm.nih.gov/pubmed/19333898", "http://www.ncbi.nlm.nih.gov/pubmed/23574525", "http://www.ncbi.nlm.nih.gov/pubmed/21279990", "http://www.ncbi.nlm.nih.gov/pubmed/22035435", "http://www.ncbi.nlm.nih.gov/pubmed/19965662", "http://www.ncbi.nlm.nih.gov/pubmed/22357358", "http://www.ncbi.nlm.nih.gov/pubmed/23861534", "http://www.ncbi.nlm.nih.gov/pubmed/22166799", "http://www.ncbi.nlm.nih.gov/pubmed/17537677", "http://www.ncbi.nlm.nih.gov/pubmed/24072968", "http://www.ncbi.nlm.nih.gov/pubmed/18975322", "http://www.ncbi.nlm.nih.gov/pubmed/22875912", "http://www.ncbi.nlm.nih.gov/pubmed/23281837", "http://www.ncbi.nlm.nih.gov/pubmed/23523202", "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "http://www.ncbi.nlm.nih.gov/pubmed/20415544", "http://www.ncbi.nlm.nih.gov/pubmed/24455520", "http://www.ncbi.nlm.nih.gov/pubmed/21878134", "http://www.ncbi.nlm.nih.gov/pubmed/19959716", "http://www.ncbi.nlm.nih.gov/pubmed/22284392", "http://www.ncbi.nlm.nih.gov/pubmed/22830347", "http://www.ncbi.nlm.nih.gov/pubmed/21711059", "http://www.ncbi.nlm.nih.gov/pubmed/19107952", "http://www.ncbi.nlm.nih.gov/pubmed/24376763", "http://www.ncbi.nlm.nih.gov/pubmed/23717217", "http://www.ncbi.nlm.nih.gov/pubmed/22776094", "http://www.ncbi.nlm.nih.gov/pubmed/21304505", "http://www.ncbi.nlm.nih.gov/pubmed/23190017", "http://www.ncbi.nlm.nih.gov/pubmed/23398911", "http://www.ncbi.nlm.nih.gov/pubmed/23170196", "http://www.ncbi.nlm.nih.gov/pubmed/23642011", "http://www.ncbi.nlm.nih.gov/pubmed/22612424", "http://www.ncbi.nlm.nih.gov/pubmed/23455231", "http://www.ncbi.nlm.nih.gov/pubmed/23094030", "http://www.ncbi.nlm.nih.gov/pubmed/23431463", "http://www.ncbi.nlm.nih.gov/pubmed/23133664" ], "ideal_answer": [ "Fostamatinib (R788) acts by inhibiting spleen tyrosine kinase. Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase that is required for the expression of a number of proinflammatory cytokines. Fostamatinib has been shown to be effective in patients with rheumatoid arthritis, leukemia, lymphoma, bronchial asthma and thrombocytopenic purpura." ], "exact_answer": [ "spleen tyrosine kinase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ], "type": "factoid", "id": "53357ca0d6d3ac6a3400004b", "snippets": [ { "offsetInBeginSection": 618, "offsetInEndSection": 806, "text": "It outlines preclinical and early clinical experiences with the Syk inhibitor fostamatinib disodium (R788) and discusses various options for further clinical development of this compound. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21438742", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 218, "text": "To assess the efficacy and safety of R788 (fostamatinib disodium), an inhibitor of spleen tyrosine kinase (Syk), in patients with active rheumatoid arthritis (RA) that did not respond to biologic therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279990", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 866, "text": "The mTOR inhibitors temsirolimus and everolimus have demonstrated antitumor activity in all types of lymphoma, the Syk inhibitor fostamatinib has activity in diffuse large B-cell lymphoma and chronic lymphocytic leukemia, and the PKC-\u03b2 inhibitor enzastaurin is being used as consolidation therapy after remission in diffuse large B-cell lymphoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21239804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Fostamatinib, a Syk-kinase inhibitor, does not affect methotrexate pharmacokinetics in patients with rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21209239", "endSection": "title" }, { "offsetInBeginSection": 88, "offsetInEndSection": 273, "text": "The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20879879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the E\u03bc- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20716772", "endSection": "title" }, { "offsetInBeginSection": 223, "offsetInEndSection": 444, "text": "We have now investigated whether inhibition of BCR signaling with the selective Syk inhibitor fostamatinib disodium (R788) will affect the growth of the leukemias that develop in the E\u03bc-TCL1 transgenic mouse model of CLL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20716772", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 378, "text": "We show that conditional ablation of the syk gene in dendritic cells (DCs) abrogates FcgammaR-mediated cross priming of diabetogenic T cells in RIP-mOVA mice, a situation phenocopied in wild-type RIP-mOVA mice treated with the selective Syk inhibitor R788.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601600", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 678, "text": "We investigated the ability of a small drug Syk inhibitor, R788, to protect mice against mesenteric ischemia-reperfusion (I/R)-induced local (intestine) and remote lung injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20522642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "The spleen tyrosine kinase (Syk) inhibitor R406 is orally administered as the prodrug R788. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20415544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19965662", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 444, "text": "These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19965662", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 540, "text": "We examined the effect of R788 (fostamatinib disodium), an oral prodrug of the selective Syk inhibitor R406, in nephrotoxic nephritis in Wistar-Kyoto rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19959716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Fostamatinib, a Syk inhibitor prodrug for the treatment of inflammatory diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333898", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Rigel Pharmaceuticals Inc is developing fostamatinib, a prodrug of the spleen tyrosine kinase (Syk) inhibitor R-406, for the potential treatment of autoimmune diseases such as rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and B-cell lymphomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333898", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 225, "text": "In developmental toxicity studies with the Syk kinase inhibitor R788, a spectrum of findings, including renal agenesis, were observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19107952", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 386, "text": "R788, a prodrug of active metabolite R406, has been shown to be an inhibitor of Syk kinase, active in a variety of in vitro and in vivo models, suggesting potential activity in the treatment of rheumatoid arthritis (RA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18975322", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 381, "text": "In collagen-induced arthritis, R788/R406, a novel and potent small molecule Syk inhibitor suppressed clinical arthritis, bone erosions, pannus formation, and synovitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17537677", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 621, "text": "Fostamatinib (R788) inhibits spleen tyrosine kinase (Syk) and has been in clinical trials involving both MTX inadequate responders (MTX-IRs) and biologic inadequate responders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23861534", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1078, "text": "The compounds that are currently investigated in patients with CLL include ibrutinib -inhibitor of Btk, fostamatinib-inhibitor of Syk and idelalisib (GS-1101) -a specific isoform of the PI3K (PI3K) inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 807, "text": "TK inhibitors including spleen TK (fostamatinib) and Janus kinases (tofacitinib) inhibitors are two novel oral therapies that have demonstrated short-term good clinical responses in active rheumatoid arthritis patients with and inadequate responses to methotrexate or other traditional (non-biologic) disease-modifying antirheumatic drugs (DMARDs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574525", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 656, "text": "Progress is also being made with orally active Syk inhibitors. One such inhibitor (fostamatinib) is currently in large-scale phase 3 trials, and there are others in clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523202", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 664, "text": "We have shown that R406, the active metabolite of the Syk inhibitor fostamatinib, induces apoptosis and cell cycle arrest while decreasing downstream phosphatidylinositol-3'-kinase (PI3K)/Akt signaling in EBV+ B cell lymphoma PTLD lines in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Effects of fostamatinib (R788), an oral spleen tyrosine kinase inhibitor, on health-related quality of life in patients with active rheumatoid arthritis: analyses of patient-reported outcomes from a randomized, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378467", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190017", "endSection": "title" }, { "offsetInBeginSection": 5, "offsetInEndSection": 194, "text": "Fostamatinib (R788) is an orally dosed prodrug designed to deliver the active metabolite R940406 (R406), a spleen tyrosine kinase (SYK) inhibitor, for the treatment of rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190017", "endSection": "abstract" }, { "offsetInBeginSection": 1318, "offsetInEndSection": 1404, "text": "Fostamatinib demonstrates rapid and extensive conversion to R406, an inhibitor of SYK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190017", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 388, "text": "Fostamatinib, a Syk inhibitor that successfully completed phase II clinical trials, also exhibits some undesirable side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23151054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase, required for the expression of a number of proinflammatory cytokines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23078058", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 865, "text": "The Syk inhibitor, fostamatinib, proved superior to placebo in Phase II trials and is currently under Phase III investigation. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055694", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 938, "text": "More recently, several KIs have been developed to target the proximal B-cell receptor (BCR) signaling pathway including spleen tyrosine kinase inhibitor (Fostamatinib) and Bruton's tyrosine kinase inhibitors (Ibrutinib, AVL-263). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22830347", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1606, "text": "Because inhibitors of SYK activity, such as fostamatinib, are in advanced clinical trials for rheumatoid arthritis and other autoimmune diseases, understanding the role of SYK in signalling via TLR4 is of immediate importance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22776094", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 999, "text": "The search terms used were Bruton's tyrosine kinase (Btk) inhibitors, PCI-32765, GDC-0834, LFM-A13, AVL-101, AVL-292, spleen tyrosine kinase (Syk) inhibitors, R343, R406, R112, R788, fostamatinib, BAY-61-3606, C-61, piceatannol, Lyn, imatinib, nilotinib, bafetinib, dasatinib, GDC-0834, PP2, SU6656 in conjunction with lymphoid malignancy, NHL, CLL, autoimmune disease, allergic disease, asthma, and rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22612424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492694", "endSection": "title" }, { "offsetInBeginSection": 744, "offsetInEndSection": 949, "text": "Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374444", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 476, "text": "In chronic lymphocytic leukemia (CLL), Syk becomes activated by external signals from the tissue microenvironment, and was targeted in a first clinical trial with R788 (fostamatinib), a relatively nonspecific Syk inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362000", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 747, "text": "In vivo expansion of luciferase(+) donor Tcs in mice developing GvHD was reduced by treatment with the Syk inhibitor Fostamatinib, which led to increased survival and reduced histologically confirmed GvHD severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22301676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Syk inhibition with fostamatinib leads to transitional B lymphocyte depletion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22284392", "endSection": "title" }, { "offsetInBeginSection": 225, "offsetInEndSection": 401, "text": "No oral biologic agents are available at this time but promising data is emerging for two drugs, tofacitinib and fostamatinib, inhibitors of JAK and Syk kinases, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22035435", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 444, "text": "Fostamatinib (R-788) is an orally bioavailable small molecule. It is the prodrug of R406, which is a potent Syk inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21711059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The oral spleen tyrosine kinase inhibitor fostamatinib attenuates inflammation and atherogenesis in low-density lipoprotein receptor-deficient mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21700926", "endSection": "title" }, { "offsetInBeginSection": 465, "offsetInEndSection": 756, "text": "Low-density lipoprotein receptor-deficient mice consuming a high-cholesterol diet supplemented with 2 doses of the orally available SYK inhibitor fostamatinib for 16 weeks showed a dose-dependent reduction in atherosclerotic lesion size by up to 59\u00b16% compared with the respective controls. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21700926", "endSection": "abstract" } ] }, { "body": "Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barr\u00e9?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25072194", "http://www.ncbi.nlm.nih.gov/pubmed/16049921", "http://www.ncbi.nlm.nih.gov/pubmed/16645971", "http://www.ncbi.nlm.nih.gov/pubmed/9703176", "http://www.ncbi.nlm.nih.gov/pubmed/11155543", "http://www.ncbi.nlm.nih.gov/pubmed/1667714", "http://www.ncbi.nlm.nih.gov/pubmed/10965158", "http://www.ncbi.nlm.nih.gov/pubmed/16155441", "http://www.ncbi.nlm.nih.gov/pubmed/15012892", "http://www.ncbi.nlm.nih.gov/pubmed/8437011", "http://www.ncbi.nlm.nih.gov/pubmed/19810856", "http://www.ncbi.nlm.nih.gov/pubmed/10511801", "http://www.ncbi.nlm.nih.gov/pubmed/26380131", "http://www.ncbi.nlm.nih.gov/pubmed/19374296", "http://www.ncbi.nlm.nih.gov/pubmed/11521055", "http://www.ncbi.nlm.nih.gov/pubmed/24513384", "http://www.ncbi.nlm.nih.gov/pubmed/18428104", "http://www.ncbi.nlm.nih.gov/pubmed/19263690", "http://www.ncbi.nlm.nih.gov/pubmed/21325125", "http://www.ncbi.nlm.nih.gov/pubmed/22447677", "http://www.ncbi.nlm.nih.gov/pubmed/3612209", "http://www.ncbi.nlm.nih.gov/pubmed/15909003", "http://www.ncbi.nlm.nih.gov/pubmed/26366317" ], "ideal_answer": [ "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia", "Miller-Fisher syndrome is a variant of Guillain-Barr\u00e9 syndrome, characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia." ], "exact_answer": "yes", "type": "yesno", "id": "571f59cd0fd6f91b68000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26380131", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 496, "text": "We are reporting a rare case of Miller-Fisher (MFS) variant of Guillain-Barr\u00e9 syndrome (GBS) as the first manifestation of SLE in a 41-year-old female", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26366317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Miller-Fisher syndrome is defined as ophthalmoplegia, ataxia and areflexia. Considered as a variant of Guillain-Barr\u00e9 syndrome, it differs in its clinical presentation and by anti-GQ1b antibody positivity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24513384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Guillain-Barr\u00e9 syndrome (GBS) and its variant, Miller Fisher syndrome (MFS), exist as several clinical subtypes with different neurological features and presentations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25072194", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 945, "text": "Using in vitro and in vivo models of the Guillain-Barr\u00e9 syndrome variant, Miller Fisher syndrome, we have shown previously that anti-GQ1b ganglioside antibodies target the presynaptic motor nerve terminal axon and surrounding perisynaptic Schwann cells, thereby mediating destructive injury through deposition of membrane attack complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16049921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Miller Fisher syndrome is a variant of Guillain-Barr\u00e9 syndrome, characterized by ophthalmoplegia, ataxia and areflexia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19810856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Miller Fisher syndrome is a localized variant of Guillain-Barr\u00e9 syndrome, characterized by ophthalmoplegia, areflexia and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16155441", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 460, "text": "Miller Fisher syndrome, a variant of Guillain-Barr\u00e9 syndrome, is associated with IgG antibody to GQ1b ganglioside.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10511801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Miller Fisher syndrome (MFS), a variant of Guillain-Barr\u00e9 syndrome, is a rare disorder typically characterized by a triad of ataxia, areflexia, and ophthalmoplegia, which may have a highly variable clinical presentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22447677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barr\u00e9 syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21325125", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 548, "text": "The objective of this study was to review the occurrence and clinical features of Guillain-Barr\u00e9 syndrome and its variant, the Miller Fisher syndrome, during TNFalpha antagonist therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16645971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Miller Fisher variant of Guillain-Barr\u00e9 syndrome masquerading as acute sphenoid sinusitis with orbital apex syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22447677", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Controversy exists concerning whether Miller Fisher syndrome (MFS) is the result of a predominantly axonal or demyelinating polyneuropathy and whether the Guillain-Barr\u00e9 syndrome variant of acute ataxia and areflexia without ophthalmoplegia, ataxic Guillain-Barr\u00e9 syndrome (atxGBS), has a distinct pathophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11155543", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 485, "text": "Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barr\u00e9 syndrome; its differential diagnosis includes Wernicke's encephalopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barr\u00e9 syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21325125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barr\u00e9 syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15909003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barr\u00e9 syndrome with pathology restricted to the peripheral nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3612209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barr\u00e9 syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15012892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and ophthalmoplegia, is generally considered as a variant of Guillain-Barr\u00e9 syndrome (GBS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10965158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Miller Fisher Syndrome (MFS), which is characterized by ophthalmoplegia, ataxia and tendon areflexia, is generally considered as a clinical variant of Guillain-Barr\u00e9 Syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1667714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Miller-Fisher syndrome (MFS), a variant of Guillain-Barr\u00e9 syndrome (GBS) is a self-limiting demyelinating disease of the peripheral nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "BACKGROUND: Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barr\u00e9 syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15909003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "BACKGROUND AND OBJECTIVE: Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barr\u00e9 syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15012892", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 491, "text": "Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barr\u00e9 syndrome; its differential diagnosis includes Wernicke's encephalopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barr\u00e9 syndrome (GBS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8437011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barr\u00e9 syndrome with pathology restricted to the peripheral nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3612209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Guillain-Barr\u00e9 syndrome (GBS), an acute inflammatory polyneuropathy, is preceded in most cases by an infectious illness, and Campylobacter jejuni, a leading cause of acute gastroenteritis, is the most common antecedent to GBS and its ocular variant, Miller Fisher syndrome (MFS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11521055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barr\u00e9 syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15909003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barr\u00e9 syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15909003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 357, "text": " The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barr\u00e9 syndrome with pathology restricted to the peripheral nervous system. A patient with Miller-Fisher syndrome and bilateral demyelinating optic neuropathy suggesting associated central nervous system pathology is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3612209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barr\u00e9 syndrome and is characterized by the clinical triad of ataxia,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21325125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": " Miller Fisher syndrome is an uncommon disease and it is a variant of Guillain-Barre syndrome. Miller Fisher syndrome also has rarer variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19263690", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 477, "text": "Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barr\u00e9 syndrome; its differential diagnosis includes Wernicke's encephalopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barr\u00e9 syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21325125", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 737, "text": "Data were separately analysed for Miller Fisher syndrome and other Guillain-Barr\u00e9 syndrome variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9703176", "endSection": "abstract" }, { "offsetInBeginSection": 1099, "offsetInEndSection": 1208, "text": "Guillain-Barr\u00e9 syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9703176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barr\u00e9 syndrome with pathology restricted to the peripheral nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3612209", "endSection": "abstract" } ] }, { "body": "Is Ctf4 involved in sister chromatid cohesion establishment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "http://www.ncbi.nlm.nih.gov/pubmed/17483413", "http://www.ncbi.nlm.nih.gov/pubmed/15598824", "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "http://www.ncbi.nlm.nih.gov/pubmed/19622120", "http://www.ncbi.nlm.nih.gov/pubmed/15485923", "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "http://www.ncbi.nlm.nih.gov/pubmed/14742710", "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "http://www.ncbi.nlm.nih.gov/pubmed/23036200" ], "ideal_answer": [ "Yes. Ctf4 is associated with the replisome and is required for proper establishment of cohesion by facilitating cohesin acetylation." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034089", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007062", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007063", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045876", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034087", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034085" ], "type": "yesno", "id": "553a5a34bc4f83e82800001a", "snippets": [ { "offsetInBeginSection": 663, "offsetInEndSection": 1151, "text": "In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4\u0394 and chl1\u0394 cells is not improved by removing Wapl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1498, "text": "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 810, "text": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Influence of the human cohesion establishment factor Ctf4/AND-1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "endSection": "title" }, { "offsetInBeginSection": 283, "offsetInEndSection": 551, "text": " Here, we used Xenopus egg extracts to show that AND-1 and Tim1-Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1-Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M-phase extracts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622120", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 880, "text": "These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17483413", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1005, "text": "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 628, "text": "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 797, "text": "WSS1 was also found to interact genetically with SGS1, TOP3, SRS2 and CTF4, which are involved in recombination, repair of replication forks and the establishment of sister chromatid cohesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15598824", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 607, "text": "The catalytic subunit of budding yeast Polalpha (Pol1p) has been shown to associate in vitro with the Spt16p-Pob3p complex, a component of the nucleosome reorganization system required for both replication and transcription, and with a sister chromatid cohesion factor, Ctf4p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15485923", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 314, "text": "Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14742710", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 858, "text": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036200", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1002, "text": "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 626, "text": "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "title" }, { "offsetInBeginSection": 140, "offsetInEndSection": 324, "text": "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 629, "text": "We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 430, "text": "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 584, "text": "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1006, "text": "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1501, "text": "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1499, "text": "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 860, "text": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Establishment of sister chromatid cohesion at the S. cerevisiae replication fork.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "endSection": "title" } ] }, { "body": "What states the second parity rule (PR2)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11164037", "http://www.ncbi.nlm.nih.gov/pubmed/10570983", "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "http://www.ncbi.nlm.nih.gov/pubmed/23140179", "http://www.ncbi.nlm.nih.gov/pubmed/10368434", "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "http://www.ncbi.nlm.nih.gov/pubmed/14732869", "http://www.ncbi.nlm.nih.gov/pubmed/12468095", "http://www.ncbi.nlm.nih.gov/pubmed/10570985", "http://www.ncbi.nlm.nih.gov/pubmed/11675607", "http://www.ncbi.nlm.nih.gov/pubmed/19861381" ], "ideal_answer": [ "The second parity rule (PR2), also known as Chargaff' s second parity rule, is an intra-strand rule which states that, when there are no biases between the two complementary strands of DNA in mutation and selection rates (substitution rates), complementary nucleotides are expected to have almost equal frequencies within single stranded DNA, namely A = T and G = C at equilibrium, without regard to the G + C content of the DNA." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010298" ], "type": "summary", "id": "55423875ec76f5e50c000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Chargaff' s second parity rule (PR2) states that complementary nucleotides are met with almost equal frequencies in single stranded DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Sueoka and Lobry declared respectively that, in the absence of bias between the two DNA strands for mutation and selection, the base composition within each strand should be A=T and C=G (this state is called Parity Rule type 2, PR2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14732869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The intra-strand Parity Rule 2 of DNA (PR2) states that A=T and G=C within each strands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12468095", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 422, "text": "deviations from the PR2 is a sign of strand-specific (or asymmetric) mutation and/or selection pressures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12468095", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 814, "text": "PR2 is an intra-strand rule where A=T and G=C are expected when there are no biases between the two complementary strands of DNA in mutation and selection rates (substitution rates)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11164037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "When there are no biases in mutation and selection between the two strands of DNA, the 12 possible substitution rates of the four nucleotides reduces to six (type 1 parity rule or PR1), and the intrastrand average base composition is expected to be A = T and G = C at equilibrium without regard to the G + C content of DNA (type 2 parity rule or PR2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 678, "text": "The second method was to plot the intrastrand bias of the third codon position from Parity Rule 2 (PR2), where A = T and G = C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10368434", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 316, "text": "The extent of deviation from intra-strand equality rule of A = T and G = C (Parity Rule 2, or PR2) is specific for individual amino acids and has been expressed as the PR2-bias fingerprint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11675607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "When there are no biases in mutation and selection between the two strands of DNA, the 12 possible substitution rates of the four nucleotides reduces to six (type 1 parity rule or PR1), and the intrastrand average base composition is expected to be A = T and G = C at equilibrium without regard to the G + C content of DNA (type 2 parity rule or PR2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Chargaff s second parity rule (PR2) states that complementary nucleotides are met with almost equal frequencies in single stranded DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The second parity rule of Chargaff (AHT and GHC within one strand) holds all over the living world with minor exceptions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23140179", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 682, "text": "The second method was to plot the intrastrand bias of the third codon position from Parity Rule 2 (PR2), where A = T and G = C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10368434", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 317, "text": "The extent of deviation from intra-strand equality rule of A = T and G = C (Parity Rule 2, or PR2) is specific for individual amino acids and has been expressed as the PR2-bias fingerprint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11675607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Chargaff' s second parity rule (PR2) states that complementary nucleotides are met with almost equal frequencies in single stranded DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The intra-strand Parity Rule 2 of DNA (PR2) states that A=T and G=C within each strands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12468095", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 681, "text": "The second method was to plot the intrastrand bias of the third codon position from Parity Rule 2 (PR2), where A = T and G = C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10368434", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 316, "text": "The extent of deviation from intra-strand equality rule of A = T and G = C (Parity Rule 2, or PR2) is specific for individual amino acids and has been expressed as the PR2-bias fingerprint", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11675607", "endSection": "abstract" } ] }, { "body": "Are retroviruses used for gene therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23921576", "http://www.ncbi.nlm.nih.gov/pubmed/23843498", "http://www.ncbi.nlm.nih.gov/pubmed/23884859", "http://www.ncbi.nlm.nih.gov/pubmed/23860311", "http://www.ncbi.nlm.nih.gov/pubmed/19435468", "http://www.ncbi.nlm.nih.gov/pubmed/21943326", "http://www.ncbi.nlm.nih.gov/pubmed/24120896", "http://www.ncbi.nlm.nih.gov/pubmed/23845947", "http://www.ncbi.nlm.nih.gov/pubmed/23845948", "http://www.ncbi.nlm.nih.gov/pubmed/23845071", "http://www.ncbi.nlm.nih.gov/pubmed/12686720", "http://www.ncbi.nlm.nih.gov/pubmed/16251873", "http://www.ncbi.nlm.nih.gov/pubmed/15912200" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0598504", "o": "http://linkedlifedata.com/resource/umls/label/A1306652" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1306651", "o": "gene transplantation for gene therapy" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/39568", "o": "Gene Therapy" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/39568", "o": "Intervention #39568 (Genetic:Gene Therapy)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/17724", "o": "gene therapy" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/17724", "o": "Intervention #17724 (Procedure:gene therapy)" } ], "ideal_answer": [ "Gene therapy is one of the most promising and active fields in therapeutic research. Gene therapy is a treatment option that introduces genetic material in vivo or ex vivo into the cells of an affected organism in order to: exchange a defective gene; manipulate a disease-related gene; or introduce an additional gene copy for overexpression of the encoded protein to generate a curative biological effect. Somatic gene therapy is gene transfer by a specific vector to a somatic cell; in contrast to germline gene therapy, the modification of the cell is restricted to the recipient and cannot be passed to her/his progeny. High efficiency of gene transfer, high specificity for the target cells, long-lasting expression of the transgene and safety without adverse reactions are the desired characteristics of an ideal vector for gene transfer.\nRetroviral (gretroviral and lentiviral) vectors have now been used in more than 350 gene-therapy studies. Retroviral vectors are particularly suited for gene-correction of cells due to long-term and stable expression of the transferred transgene(s), and also because little effort is required for their cloning and production. Several monogenic inherited diseases, mostly immunodeficiencies, can now be successfully treated." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012191", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016458", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012190", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015316", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012192" ], "type": "yesno", "id": "52ce531f03868f1b06000031", "snippets": [ { "offsetInBeginSection": 401, "offsetInEndSection": 600, "text": "Several immunodeficiencies have been treated successfully by stem cell-targeted, retroviral-mediated gene transfer with reconstitution of the immune system following infusion of the transduced cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843498", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 809, "text": "In this work we have developed and tested a self-inactivating (SIN) gammaretroviral vector (SINfes.gp91s) containing a codon-optimized transgene (gp91(phox)) under the transcriptional control of a myeloid promoter for the gene therapy of the X-linked form of CGD (X-CGD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845071", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 529, "text": " We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845947", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 459, "text": "We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845948", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 307, "text": "We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23884859", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 506, "text": "gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23921576", "endSection": "abstract" } ] }, { "body": "Do lincRNAs play a role in human cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22493738", "http://www.ncbi.nlm.nih.gov/pubmed/23226159", "http://www.ncbi.nlm.nih.gov/pubmed/21151178", "http://www.ncbi.nlm.nih.gov/pubmed/22258142", "http://www.ncbi.nlm.nih.gov/pubmed/23395002", "http://www.ncbi.nlm.nih.gov/pubmed/23281836", "http://www.ncbi.nlm.nih.gov/pubmed/23354591", "http://www.ncbi.nlm.nih.gov/pubmed/23153939", "http://www.ncbi.nlm.nih.gov/pubmed/21327457", "http://www.ncbi.nlm.nih.gov/pubmed/22454180", "http://www.ncbi.nlm.nih.gov/pubmed/23443164", "http://www.ncbi.nlm.nih.gov/pubmed/23208419", "http://www.ncbi.nlm.nih.gov/pubmed/22614017", "http://www.ncbi.nlm.nih.gov/pubmed/23133536", "http://www.ncbi.nlm.nih.gov/pubmed/20393566", "http://www.ncbi.nlm.nih.gov/pubmed/22285928", "http://www.ncbi.nlm.nih.gov/pubmed/23267367", "http://www.ncbi.nlm.nih.gov/pubmed/22363342", "http://www.ncbi.nlm.nih.gov/pubmed/23292722", "http://www.ncbi.nlm.nih.gov/pubmed/21991387" ], "ideal_answer": [ "Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. The best-studied examples include HOTAIR, a negative prognostic factor that exhibits pro-oncogenic activity in a variety of human cancers, CRNDE the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding), a long non-coding RNA (lncRNA) gene that expresses multiple splice variants and displays a very tissue-specific pattern of expression and ANRIL, a lincRNA that is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene." ], "exact_answer": "yes", "type": "yesno", "id": "516e5f33298dcd4e5100007e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Long non-coding RNA H19 increases bladder cancer metastasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354591", "endSection": "title" }, { "offsetInBeginSection": 554, "offsetInEndSection": 685, "text": "These data suggest that upregulated H19 enhances bladder cancer metastasis by associating with EZH2 and inhibiting E-cad expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354591", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "lncRNA H19 is essential for human tumor growth", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354591", "endSection": "sections.0" }, { "offsetInBeginSection": 200, "offsetInEndSection": 386, "text": "Previous reports have demonstrated that HOTAIR associates with chromatin modifications in cooperation with the Polycomb complex PRC2, and promotes breast and colorectal cancer metastasis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23292722", "endSection": "sections.0" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1172, "text": "although the clinical significance of HOTAIR expression in HCC may not be as pronounced as that in breast and colorectal cancers, the current study demonstrates that HOTAIR expression is associated with HCC progression, warranting further studies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23292722", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281836", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 118, "text": "Long non-coding RNA influences radiosensitivity of colorectal carcinoma cell lines by regulating cyclin D1 expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454180", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Long non-coding RNA urothelial carcinoma associated 1 (UCA1) promotes human bladder cancer cell proliferation, but the underlying mechanism remains unknown", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22285928", "endSection": "sections.0" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1062, "text": "UCA1 regulated cell cycle through CREB via PI3K-AKT dependent pathway in bladder cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22285928", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22285928", "endSection": "title" }, { "offsetInBeginSection": 656, "offsetInEndSection": 808, "text": "overexpression of Yiya promotes cell cycle progression at the G1/S transition, therefore identifying Yiya as a cell-cycle-associated long non-coding RNA", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258142", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 314, "text": "The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21327457", "endSection": "sections.0" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1544, "text": "The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21327457", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151178", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "A 42\u2009kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16(INK4A), p14(ARF) and p15(INK4B), and is altered in an estimated 30-40% of human tumors", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151178", "endSection": "sections.0" }, { "offsetInBeginSection": 921, "offsetInEndSection": 1101, "text": "These results advance our understanding of the role of lncRNA-LET as a regulator of hypoxia signaling and\u00a0offer new avenues for therapeutic intervention against cancer progression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395002", "endSection": "sections.0" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1729, "text": "Silencing MALAT1 is a potential novel therapeutic approach for this cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153939", "endSection": "sections.0" } ] }, { "body": "Explain the concept proteostasis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23463216", "http://www.ncbi.nlm.nih.gov/pubmed/24126073", "http://www.ncbi.nlm.nih.gov/pubmed/23894132", "http://www.ncbi.nlm.nih.gov/pubmed/23119163", "http://www.ncbi.nlm.nih.gov/pubmed/23479439", "http://www.ncbi.nlm.nih.gov/pubmed/23746257", "http://www.ncbi.nlm.nih.gov/pubmed/24116849", "http://www.ncbi.nlm.nih.gov/pubmed/24094931", "http://www.ncbi.nlm.nih.gov/pubmed/23833797", "http://www.ncbi.nlm.nih.gov/pubmed/23986914", "http://www.ncbi.nlm.nih.gov/pubmed/24079818", "http://www.ncbi.nlm.nih.gov/pubmed/23986815" ], "ideal_answer": [ "Protein homeostasis, or proteostasis, refers to a proper balance between synthesis, maturation, and degradation of cellular proteins. Disruption of proteostasis is implicated in aging and the pathogenesis of numerous degenerative diseases." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057165" ], "type": "summary", "id": "55048939f8aee20f27000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Protein homeostasis, or proteostasis, refers to a proper balance between synthesis, maturation, and degradation of cellular proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24126073", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 240, "text": "Mechanisms that promote the homeostasis of the proteome, or proteostasis, can slow aging and decrease the incidence of age-related diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24094931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 468, "text": "The eukaryotic cell possesses specialized pathways to turn over and degrade redundant proteins and organelles. Each pathway is unique and responsible for degradation of distinctive cytosolic material. The ubiquitin-proteasome system and autophagy (chaperone-mediated, macro, micro and organelle specific) act synergistically to maintain proteostasis. Defects in this equilibrium can be deleterious at cellular and organism level, giving rise to various disease states.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24116849", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 268, "text": " protein homeostasis (proteostasis) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24079818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The folding biology common to all three kingdoms of life (Archaea, Bacteria, and Eukarya) is proteostasis. The proteostasis network (PN) functions as a \u201ccloud\u201d to generate, protect, and degrade the proteome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23986914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Maintaining the dynamic proteome of a living cell in the face of an ever-changing environment depends on a fine-tuned balance of protein synthesis and protein degradation. Molecular chaperones exert key functions during protein homeostasis (proteostasis). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23986815", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 631, "text": "This research highlighted the central importance of protein homeostasis, or proteostasis for short, defined as the cellular state in which the proteome is both stable and functional. It implicates an equilibrium between synthesis, folding, trafficking, aggregation, disaggregation and degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Protein homeostasis, also called proteostasis, is critical for cellular health and its dysregulation is implicated in aging, cancer, metabolic disease, and neurodegenerative disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23833797", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 174, "text": " protein homeostasis (proteostasis) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746257", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 343, "text": " Disruption of proteostasis is implicated in aging and the pathogenesis of numerous degenerative diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Protein homeostasis, proteostasis, is essential to understand cell function. Protein degradation is a crucial component of the proteostatic mechanisms of the cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23119163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 494, "text": "Maintaining correct cellular function is a fundamental biological process for all forms of life. A critical aspect of this process is the maintenance of protein homeostasis (proteostasis) in the cell, which is largely performed by a group of proteins, referred to as the protein quality control (PQC) network. This network of proteins, comprised of chaperones and proteases, is critical for maintaining proteostasis not only during favourable growth conditions, but also in response to stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23479439", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 521, "text": "All organisms--Bacteria, Archaea and Eukarya--have evolved a protein homeostasis, or proteostasis, network comprising chaperones and folding factors, degradation components, signalling pathways and specialized compartmentalized modules that manage protein folding in response to environmental stimuli and variation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463216", "endSection": "abstract" } ] }, { "body": "Which gene test can be used for the X-linked myotubular myopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17005396", "http://www.ncbi.nlm.nih.gov/pubmed/20434914", "http://www.ncbi.nlm.nih.gov/pubmed/10714588", "http://www.ncbi.nlm.nih.gov/pubmed/17621527", "http://www.ncbi.nlm.nih.gov/pubmed/9450905", "http://www.ncbi.nlm.nih.gov/pubmed/19084976", "http://www.ncbi.nlm.nih.gov/pubmed/8664565", "http://www.ncbi.nlm.nih.gov/pubmed/12391329", "http://www.ncbi.nlm.nih.gov/pubmed/20682747", "http://www.ncbi.nlm.nih.gov/pubmed/22068590", "http://www.ncbi.nlm.nih.gov/pubmed/12031625", "http://www.ncbi.nlm.nih.gov/pubmed/9736772", "http://www.ncbi.nlm.nih.gov/pubmed/9541111", "http://www.ncbi.nlm.nih.gov/pubmed/14660569", "http://www.ncbi.nlm.nih.gov/pubmed/11456308", "http://www.ncbi.nlm.nih.gov/pubmed/10063835", "http://www.ncbi.nlm.nih.gov/pubmed/18434328", "http://www.ncbi.nlm.nih.gov/pubmed/10323249", "http://www.ncbi.nlm.nih.gov/pubmed/19846786", "http://www.ncbi.nlm.nih.gov/pubmed/22987702", "http://www.ncbi.nlm.nih.gov/pubmed/22435031", "http://www.ncbi.nlm.nih.gov/pubmed/18358876", "http://www.ncbi.nlm.nih.gov/pubmed/23390130", "http://www.ncbi.nlm.nih.gov/pubmed/9781038", "http://www.ncbi.nlm.nih.gov/pubmed/9305655", "http://www.ncbi.nlm.nih.gov/pubmed/10502779", "http://www.ncbi.nlm.nih.gov/pubmed/23346162", "http://www.ncbi.nlm.nih.gov/pubmed/21488203", "http://www.ncbi.nlm.nih.gov/pubmed/11001925" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A16765414", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10788614", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0410203", "o": "http://linkedlifedata.com/resource/umls/label/A11987180" } ], "ideal_answer": [ "Genetic testing of the MTM1 gene can be used for the X-linked myotubular myopathy." ], "exact_answer": [ "MTM1 gene test" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020914", "http://www.disease-ontology.org/api/metadata/DOID:14717", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "factoid", "id": "51542dabd24251bc0500007d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068590", "endSection": "sections.0" }, { "offsetInBeginSection": 169, "offsetInEndSection": 338, "text": "As a gene for X linked MTM was recently identified in Xq28, we screened the obligatory carrier mothers for mutation. We found a 4 bp deletion in exon 4 of the MTM1 gene,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9541111", "endSection": "sections.0" }, { "offsetInBeginSection": 88, "offsetInEndSection": 266, "text": "X-linked Myotubular Myopathy has clearly shown the benefits to be gained from a multinational research consortium with a common interest in identifying and cloning the MTM1 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8664565", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Myotubular myopathy (MTM1) is an X-linked disease, characterized by severe neonatal hypotonia and generalized muscle weakness, with pathological features suggesting an impairment in maturation of muscle fibres. The MTM1 gene encodes a protein (myotubularin) with a phosphotyrosine phosphatase consensus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11001925", "endSection": "sections.0" }, { "offsetInBeginSection": 154, "offsetInEndSection": 272, "text": "myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390130", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 276, "text": "We established a colony of dogs that harbor an X-linked MTM1 missense mutation.Muscle from affected male dogs exhibits reduction and altered localization of the MTM1 gene product, myotubularin, and provides a model analogous to X-linked myotubular myopathy (XLMTM)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987702", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy, usually characterized by severe hypotonia and respiratory insufficiency at birth, in affected, male infants. The disease is causally associated with mutations in the MTM1 gene, coding for phosphatase myotubularin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22435031", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682747", "endSection": "sections.0" }, { "offsetInBeginSection": 690, "offsetInEndSection": 908, "text": "MTM1 gene sequencing revealed a unique exon 7 variant in all seven affected males, causing a nonconservative missense change, p.N155K, which haplotype data suggest derives from a recent founder in the local population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682747", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "X-linked centronuclear myopathy (XLMTM), also called myotubular myopathy, is a severe congenital myopathy characterized by generalized hypotonia and weakness at birth and the typical histological finding of centralization of myo-nuclei. It is caused by mutations in the MTM1 gene encoding the 3-phosphoinositides phosphatase myotubularin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20434914", "endSection": "sections.0" }, { "offsetInBeginSection": 551, "offsetInEndSection": 576, "text": "sequencing all MTM1 exons", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20434914", "endSection": "sections.0" }, { "offsetInBeginSection": 377, "offsetInEndSection": 620, "text": "X-linked myotubular myopathy (XLMTM), a severe congenital disorder due to loss of function mutations in the MTM1 gene, encoding myotubularin, a phosphoinositide phosphatase thought to have a role in plasma membrane homeostasis and endocytosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19846786", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "Mutations in the gene encoding the phosphoinositide phosphatase myotubularin 1 protein (MTM1) are usually associated with severe neonatal X-linked myotubular myopathy (XLMTM). However, mutations in MTM1 have also been recognized as the underlying cause of \"atypical\" forms of XLMTM in newborn boys, female infants, female manifesting carriers and adult men.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19084976", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 273, "text": "X-linked myotubular myopathy (XLMTM), a recessive disorder, is caused by mutations affecting the myotubulatin (MTM1) gene located on the X chromosome. Most of the affected males die in the early postnatal period whereas female carriers are usually asymptomatic.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18358876", "endSection": "sections.0" }, { "offsetInBeginSection": 114, "offsetInEndSection": 197, "text": "The authors present a patient with the most severe X-linked recessive type (XLMTM).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17621527", "endSection": "sections.0" }, { "offsetInBeginSection": 380, "offsetInEndSection": 542, "text": "The diagnosis was confirmed and further specified by genetic analysis, revealing a novel frameshift mutation (1314-1315insT) of the myotubularin-coding MTM1 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17621527", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "X-linked myotubular myopathy (XLMTM) is a congenital muscle disorder caused by mutations in the MTM1 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17005396", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "MTM1, the gene encoding myotubularin (MTM1), is mutated in the X-linked myotubular myopathy (XLMTM), a severe genetic muscular disorder", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14660569", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Myotubularin is a ubiquitously expressed phosphatase that acts on phosphatidylinositol 3-monophosphate [PI(3)P], a lipid implicated in intracellular vesicle trafficking and autophagy. It is encoded by the MTM1 gene, which is mutated in X-linked myotubular myopathy (XLMTM), a muscular disorder characterized by generalized hypotonia and muscle weakness at birth leading to early death of most affected males.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12391329", "endSection": "sections.0" }, { "offsetInBeginSection": 776, "offsetInEndSection": 870, "text": "The entire coding sequence of the gene was screened in 10 XLMTM patients using this technique.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12031625", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "X-linked myotubular myopathy (XLMTM; OMIM# 310400) is a severe congenital muscle disease caused by mutations in the myotubularin (MTM1) gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12031625", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Mutations in the MTM1 gene cause X-linked recessive myotubular myopathy (XLMTM; MIM310400).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11456308", "endSection": "sections.0" }, { "offsetInBeginSection": 445, "offsetInEndSection": 666, "text": "We screened 29 independant patients with XLMTM phenotype and four with centronuclear myopathy. 87% (21/24) of patients with known MTM1 mutations showed abnormal myotubularin levels, including some with missense mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11456308", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "X-linked myotubular myopathy (XLMTM) characteristically causes severe or fatal muscle weakness in male infants. Mutations in the gene MTM1, encoding the protein myotubularin, can be identified in most families.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10714588", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "X-linked myotubular myopathy (XLMTM) is a congenital muscular disease characterized by severe hypotonia and generalized muscle weakness, leading in most cases to early postnatal death. The gene responsible for the disease, MTM1, encodes a dual specificity phosphatase, named myotubularin, which is highly conserved throughout evolution.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502779", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "X-linked recessive myotubular myopathy (XLMTM) is a muscle disorder usually affecting newborn males. In the majority of cases, muscle weakness and hypotonia lead to a rapid demise at neonatal age. The responsible MTM1 gene is located in proximal Xq28.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10323249", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due to mutations in the MTM1 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9736772", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "X-linked recessive myotubular myopathy (XLMTM) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. The gene responsible, MTM1, was identified recently by positional cloning, and encodes a protein (myotubularin) with a tyrosine phosphatase domain (PTP).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9305655", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 557, "text": "X-linked recessive myotubular myopathy (XLMTM; MTM1) is a severe neonatal disorder often causing perinatal death of the affected males. The responsible gene, designated MTM1, was localized to proximal Xq28 and recently isolated. The characterization of MTM1 allowed us to screen for causing mutations in three families, previously investigated by linkage analysis. Using exon amplification, single strand conformation polymorphism, and subsequent sequencing analysis, three new mutations and their mutational origin were characterized by analyzing 10 exons.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9450905", "endSection": "sections.0" } ] }, { "body": "Is there a phylogenetic analysis for HIV?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24205972", "http://www.ncbi.nlm.nih.gov/pubmed/22978157", "http://www.ncbi.nlm.nih.gov/pubmed/24273040", "http://www.ncbi.nlm.nih.gov/pubmed/22918554", "http://www.ncbi.nlm.nih.gov/pubmed/24223905", "http://www.ncbi.nlm.nih.gov/pubmed/24220189", "http://www.ncbi.nlm.nih.gov/pubmed/22924643", "http://www.ncbi.nlm.nih.gov/pubmed/22899432", "http://www.ncbi.nlm.nih.gov/pubmed/19245688", "http://www.ncbi.nlm.nih.gov/pubmed/23555898", "http://www.ncbi.nlm.nih.gov/pubmed/24171696", "http://www.ncbi.nlm.nih.gov/pubmed/22162803", "http://www.ncbi.nlm.nih.gov/pubmed/23015735", "http://www.ncbi.nlm.nih.gov/pubmed/22903393", "http://www.ncbi.nlm.nih.gov/pubmed/23555203", "http://www.ncbi.nlm.nih.gov/pubmed/22996031", "http://www.ncbi.nlm.nih.gov/pubmed/22981618" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7584997", "o": "C18940" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7584997", "o": "Phylogenetics" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1519068", "o": "http://linkedlifedata.com/resource/umls/label/A7658697" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1519068", "o": "http://linkedlifedata.com/resource/umls/label/A7658697" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1519068", "o": "http://linkedlifedata.com/resource/umls/label/A7584997" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7658697", "o": "Phylogenetic Analysis" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7658697", "o": "C18940" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7584997", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7658697", "o": "NCI Thesaurus" } ], "ideal_answer": [ "In biology, phylogenetics is the study of evolutionary relationships among groups of organisms (e.g. species, populations), which are discovered through molecular sequencing data and morphological data matrices. The result of phylogenetic studies is a hypothesis about the evolutionary history of taxonomic groups: their phylogeny. \nPhylogenetic analysis examines small differences in HIV\u2019s genes using computational methods to calculate the genetic distance between strains. Unlike\nhuman DNA, which remains stable for a lifetime, HIV\u2019s RNA changes very rapidly, leading to a huge amount of genetic diversity. This diversity means that scientists, using phylogenetic analysis, have been able to ascertain where HIV comes from, as well as track the various strains of HIV that exist worldwide.\nBased on results, there are found many studies on HIV phylogenetic analysis." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006678", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010802", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058974" ], "type": "yesno", "id": "53354eafd6d3ac6a34000044", "snippets": [ { "offsetInBeginSection": 668, "offsetInEndSection": 859, "text": "The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015735", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 424, "text": "Phylogenetic trees were constructed to evaluate the relationships between the variants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22996031", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 663, "text": "We analyzed pol (protease/reverse transcriptase) sequences from 135 newly diagnosed HIV-1-infected patients during the years 2009-2011. For phylogenetic relationships, sequences were aligned to the most recent reference data set from the Los Alamos database using BioEdit (version 7.1.3). The resulting alignment was analyzed with the Phylip package (version 3.67) building a neighbor-joining tree based on the Kimura two-parameter substitution model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981618", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 663, "text": ". Phylogenetic analysis of gag gene were then performed using the MEGA 3.1 software, the gene distances were calculated by Distance program. There were three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among twenty four MSMs in Zhengzhou", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22978157", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 883, "text": "Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22924643", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 423, "text": " We evaluated the risk factors for intrafamilial transmission of HIV-1 infection through qualitative epidemiology following pol and env gene sequencing and phylogenetic analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918554", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 587, "text": "Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903393", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 546, "text": "Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22899432", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 601, "text": "DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273040", "endSection": "abstract" }, { "offsetInBeginSection": 47, "offsetInEndSection": 219, "text": " (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273040", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 574, "text": "The aim of this study was to investigate the phylogenetic relationships of HIV-1 subtype C strains from Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24223905", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 521, "text": " This study characterized HCV genotype 5 sequences from South Africa, including six near full-length genomes, as well as the E1 region from an additional 12 genotype 5 samples. Phylogenetic analysis of these near full-length genome sequences revealed that all genotype 5 sequences formed a close cluster with high bootstrap support", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24220189", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 603, "text": " The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24205972", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 758, "text": " Finally, a phylogenetic tree was constructed to elucidate the observed pattern of HIV TDR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171696", "endSection": "abstract" } ] }, { "body": "What is the association between adiponectin and migraine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24648004", "http://www.ncbi.nlm.nih.gov/pubmed/18474846", "http://www.ncbi.nlm.nih.gov/pubmed/19556389", "http://www.ncbi.nlm.nih.gov/pubmed/24819919", "http://www.ncbi.nlm.nih.gov/pubmed/19845784", "http://www.ncbi.nlm.nih.gov/pubmed/17448181", "http://www.ncbi.nlm.nih.gov/pubmed/20200812", "http://www.ncbi.nlm.nih.gov/pubmed/19882941", "http://www.ncbi.nlm.nih.gov/pubmed/24820828", "http://www.ncbi.nlm.nih.gov/pubmed/23489216", "http://www.ncbi.nlm.nih.gov/pubmed/25378672", "http://www.ncbi.nlm.nih.gov/pubmed/24250893", "http://www.ncbi.nlm.nih.gov/pubmed/22823862", "http://www.ncbi.nlm.nih.gov/pubmed/17515549" ], "ideal_answer": [ "There is evidence to suggest that adiponectin plays a role in migraine. Increase in body fat elevates adiponectin and leptin secretion which in turn impair inflammatory processes that could be contributing to migraine risk. In episodic migraine patients, adiponectin was associated with migraine severity and predictive of acute treatment response. Serum adiponectin levels are increased in women chronic daily headache sufferers." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:6364", "http://www.uniprot.org/uniprot/ADIPO_HUMAN", "http://www.uniprot.org/uniprot/ADIPO_MOUSE", "http://www.uniprot.org/uniprot/ADIPO_BOVIN" ], "type": "summary", "id": "55031d82e9bde6963400002c", "snippets": [ { "offsetInBeginSection": 65, "offsetInEndSection": 253, "text": "Increase in body fat, especially in gluteofemoral region, elevates adiponectin and leptin secretion which in turn impair inflammatory processes that could be contributing to migraine risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24250893", "endSection": "abstract" }, { "offsetInBeginSection": 2064, "offsetInEndSection": 2350, "text": "CONCLUSION: In this pilot study of women episodic migraineurs, the HMW\u2009:\u2009LMW ADP ratio level was associated with migraine severity and predictive of acute treatment response. ADP and the HMW\u2009:\u2009LMW ratio of ADP represent potential novel biomarkers and drug targets for episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23489216", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 842, "text": "Specifically, neurotransmittors such as serotonin, peptides such as orexin, and adipocytokines such as adiponectin and leptin have been suggested to have roles in both feeding and migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22823862", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1158, "text": "Obesity can be considered as a proinflammatory state in which increased inflammatory mediators, vascular hyperreactivity, plasma calcitonin gene-related peptide (CGRP) concentrations and decreased adiponectin concentrations are observed. These alterations can cause an increase in the frequency of migraine attacks developed of central sensitization, and thereafter, chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19882941", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 682, "text": "Specifically, neurotransmittors such as serotonin, peptides such as orexin, and adipocytokines such as adiponectin and leptin have been suggested to have roles in both feeding and migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19845784", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 507, "text": "Several adipocytokines appear to play an integral role in feeding and obesity--and have also been linked to pain. Among these proteins are adiponectin and leptin. The author reviews the regulation of adipose tissue and feeding and provides an in-depth examination of adiponectin and leptin and their association with migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19556389", "endSection": "abstract" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1720, "text": "CONCLUSION: Serum adiponectin levels are increased in women chronic daily headache (CDH) sufferers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18474846", "endSection": "abstract" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1741, "text": "n this review we discuss the basic science of adiponectin and its potential connection to the pathophysiology of migraine. Future research may focus on how adiponectin levels are potentially altered during migraine attacks, and how that information can be potentially translated into migraine therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17448181", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1004, "text": "Collectively, the results of our analysis suggest that a link between serum adiponectin and migraine remains elusive, at the best", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24648004", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1741, "text": "Future research may focus on how adiponectin levels are potentially altered during migraine attacks, and how that information can be potentially translated into migraine therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17448181", "endSection": "abstract" } ] }, { "body": "Which phenomenon is described as oncogene addiction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16857816", "http://www.ncbi.nlm.nih.gov/pubmed/16869776", "http://www.ncbi.nlm.nih.gov/pubmed/21974937", "http://www.ncbi.nlm.nih.gov/pubmed/22647359", "http://www.ncbi.nlm.nih.gov/pubmed/23532334", "http://www.ncbi.nlm.nih.gov/pubmed/21828272", "http://www.ncbi.nlm.nih.gov/pubmed/22312254", "http://www.ncbi.nlm.nih.gov/pubmed/22235994", "http://www.ncbi.nlm.nih.gov/pubmed/21575270", "http://www.ncbi.nlm.nih.gov/pubmed/18451131", "http://www.ncbi.nlm.nih.gov/pubmed/18451130", "http://www.ncbi.nlm.nih.gov/pubmed/20173739", "http://www.ncbi.nlm.nih.gov/pubmed/21969595", "http://www.ncbi.nlm.nih.gov/pubmed/22860051", "http://www.ncbi.nlm.nih.gov/pubmed/23637683" ], "ideal_answer": [ " Oncogene addiction describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. We propose that addiction may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call oncogenic shock, prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death. ", "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. \"Addiction\" may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call \"oncogenic shock,\" prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009857" ], "type": "summary", "id": "55253d7087ecba3764000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Tumor cell growth and survival can often be impaired by inactivating a single oncogen- a phenomenon that has been called as \"oncogene addiction.\" It is in such scenarios that molecular targeted therapies may succeed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23637683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The clinical efficacy of tyrosine kinase inhibitors supports the dependence of distinct subsets of cancers on specific driver mutations for survival, a phenomenon called \"oncogene addiction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23532334", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 335, "text": "A given tumor is usually dependent on the oncogene that is activated in the respective tumor entity. This phenomenon called oncogene addiction provides the rationale for attempts to target oncogene products in a therapeutic manner, be it by small molecules, by small interfering RNAs (siRNA) or by antigen-specific T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22860051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "It has long been established that cancers can become addicted to particular oncogenes. Despite the genetic complexity that governs tumorigenesis, certain cancers can exhibit a critical dependency on the expression of a single oncogene, which when removed leads to death of the cancer cell. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647359", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 1279, "text": "We now know that oncogenes are dysfunctional proto-oncogenes and that dysfunctional tumor suppressor genes contribute to the cancer process. Furthermore, Weinstein and others have hypothesized the phenomenon of oncogene addiction as a distinct characteristic of the malignant cell. It can be assumed that cancer cells, indeed, become dependent on such vital oncogenes. The products of these vital oncogenes, such as c-myc, may well be the Achilles heel by which targeted molecular therapy may lead to truly personalized cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22312254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 524, "text": "Despite complex genomic and epigenetic abnormalities, many cancers are irrevocably dependent on an initiating oncogenic lesion whose restoration to a normal physiological activation can elicit a dramatic and sudden reversal of their neoplastic properties. This phenomenon of the reversal of tumorigenesis has been described as oncogene addiction. Oncogene addiction had been thought to occur largely through tumour cell-autonomous mechanisms such as proliferative arrest, apoptosis, differentiation and cellular senescence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22235994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "Cancers can exhibit marked tumor regression after oncogene inhibition through a phenomenon called \"oncogene addiction.\" The ability to predict when a tumor will exhibit oncogene addiction would be useful in the development of targeted therapeutics. Oncogene addiction is likely the consequence of many cellular programs. However, we reasoned that many of these inputs may converge on aggregate survival and death signals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21974937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and/or apoptosis, a phenomenon known as oncogene addiction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21969595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 470, "text": "Although human cancers have complex genotypes and are genomically unstable, they often remain dependent on the continued presence of single-driver mutations-a phenomenon dubbed \"oncogene addiction.\" Such dependencies have been demonstrated in mouse models, where conditional expression systems have revealed that oncogenes able to initiate cancer are often required for tumor maintenance and progression, thus validating the pathways they control as therapeutic targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21828272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Oncogene addiction is a phenomenon that the survival of cancer cells depends on an activated oncogene or inactivation of tumor suppressor gene, and is regarded as the 'Achilles heel' of the successful molecular targeted therapies in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21575270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Inhibition of an initiating oncogene often leads to extensive tumour cell death, a phenomenon known as oncogene addiction. This has led to the search for compounds that specifically target and inhibit oncogenes as anticancer agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 761, "text": "Cancer is a multistep process whereby genetic events that result in the activation of proto-oncogenes or the inactivation of tumor suppressor genes usurp physiologic programs mandating relentless proliferation and growth. Experimental evidence surprisingly illustrates that the inactivation of even a single oncogene can be sufficient to induce sustained tumor regression. These observations suggest the hypothesis that tumors become irrevocably addicted to the oncogenes that initiated tumorigenesis. The proposed explanation for this phenomenon is that activated oncogenes result in a signaling state in which the sudden abatement of oncogene activity balances towards proliferative arrest and apoptosis. Indeed, substantial evidence supports this hypothesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18451131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Cancer cells contain multiple genetic and epigenetic abnormalities. Despite this complexity, their growth and survival can often be impaired by the inactivation of a single oncogene. This phenomenon, called \"oncogene addiction,\" provides a rationale for molecular targeted therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18451130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This question has been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth of large tumors that regress completely upon oncogene inactivation--a phenomenon called oncogene addiction. We assemble here the evidence that oncogene addiction is angiogenesis-dependent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16869776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 738, "text": "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. We propose that \"addiction\" may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call \"oncogenic shock,\" prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16857816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This question has been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth of large tumors that regress completely upon oncogene inactivation--a phenomenon called oncogene addiction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16869776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16857816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Oncogene addiction is a phenomenon that the survival of cancer cells depends on an activated oncogene or inactivation of tumor suppressor gene, and is regarded as the Achilles heel of the successful molecular targeted therapies in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21575270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16857816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Does an activated oncogene that initiates tumor growth need to remain activated to maintain the cancer phenotype? This question has been answered affirmatively by experiments in which doxycycline-regulated oncogene activation induces growth of large tumors that regress completely upon oncogene inactivation--a phenomenon called oncogene addiction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16869776", "endSection": "abstract" } ] }, { "body": "Are there randomised controlled trials on sevoflurane?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16867087", "http://www.ncbi.nlm.nih.gov/pubmed/21733178", "http://www.ncbi.nlm.nih.gov/pubmed/20683334", "http://www.ncbi.nlm.nih.gov/pubmed/12693995", "http://www.ncbi.nlm.nih.gov/pubmed/23452265", "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "http://www.ncbi.nlm.nih.gov/pubmed/21675061", "http://www.ncbi.nlm.nih.gov/pubmed/15310345", "http://www.ncbi.nlm.nih.gov/pubmed/22103571", "http://www.ncbi.nlm.nih.gov/pubmed/11966554" ], "ideal_answer": [ "Yes. There are < 10 studies reported, answering questions like : how to improve speed of recovery, relationship to dreaming and anesthetic experience, effect on cardiac troponin release, effect on myocardial injury, postoperative delirium, haemodynamics & emergence and recovery characteristics of total intravenous anaesthesia, costs of postoperative nausea and vomiting, pediatric conscious sedation for dental procedures" ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4252326" ], "type": "yesno", "id": "515d9e5c298dcd4e5100000e", "snippets": [ { "offsetInBeginSection": 459, "offsetInEndSection": 641, "text": "After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452265", "endSection": "sections.0" }, { "offsetInBeginSection": 1471, "offsetInEndSection": 1617, "text": "Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452265", "endSection": "sections.0" }, { "offsetInBeginSection": 329, "offsetInEndSection": 569, "text": "A total of 200 women undergoing first trimester abortion (American Society of Anesthesiologists physical status I) participated in the study. Patients were randomly assigned to receive either sevoflurane or propofol for short-term sedation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "endSection": "sections.0" }, { "offsetInBeginSection": 650, "offsetInEndSection": 841, "text": "The results showed the incidence of dreaming was significantly different between anaesthesia groups with 60% (60/100) of the sevoflurane group and 33% (33/100) of the propofol group (P=0.000)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "endSection": "sections.0" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1569, "text": "Anaesthesia administered had no effect on patient satisfaction. The results suggest that the incidence of dreaming was not affected by recovery time. Patient satisfaction was not influenced by choice of sedative and/or by the occurrence of dreaming during sevoflurane or propofol short-term sedation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Prior reports suggest that dreaming during anaesthesia is dependent on recovery time. Dreaming during sedation may impact patient satisfaction", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22103571", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 373, "text": "We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22103571", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Myocardial injury in remifentanil-based anaesthesia for off-pump coronary artery bypass surgery: an equipotent dose of sevoflurane versus propofol", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21675061", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "This randomised controlled trial compared the effect of equipotent anaesthetic doses of sevoflurane (S group) versus propofol (P group), during remifentanil-based anaesthesia for off-pump coronary artery bypass surgery, on myocardial injury. Either sevoflurane or propofol was titrated to maintain bispectral index values between 40 and 50.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21675061", "endSection": "sections.0" }, { "offsetInBeginSection": 365, "offsetInEndSection": 545, "text": "This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20683334", "endSection": "sections.0" }, { "offsetInBeginSection": 654, "offsetInEndSection": 747, "text": "Patients were randomly allocated to receive sugammadex 2.0 mg kg(-1) or neostigmine 50 microg", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20683334", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "We compared the haemodynamics, emergence and recovery characteristics of total intravenous anaesthesia using propofol/remifentanil with sevoflurane/remifentanil anaesthesia, under bispectral index guidance, in 103 patients undergoing surgical procedures lasting > 3.5 h", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16867087", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "A randomised controlled trial of paediatric conscious sedation for dental treatment using intravenous midazolam combined with inhaled nitrous oxide or nitrous oxide/sevoflurane", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15310345", "endSection": "title" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1643, "text": "Intravenous midazolam, especially in combination with inhaled nitrous oxide or sevoflurane and nitrous oxide, are effective techniques, with the combination of midazolam and sevoflurane the one most likely to result in successful treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15310345", "endSection": "sections.0" }, { "offsetInBeginSection": 114, "offsetInEndSection": 244, "text": "We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12693995", "endSection": "sections.0" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1174, "text": "In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12693995", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for inhalation conscious sedation in children having dental treatment: a randomised controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11966554", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "We studied 411 children aged 3-10 years who were referred for dental treatment. They were randomly allocated to have inhalation conscious sedation with either sevoflurane/nitrous oxide mixture or nitrous oxide alone", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11966554", "endSection": "sections.0" } ] }, { "body": "In which cells are gasdermins expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19051310", "http://www.ncbi.nlm.nih.gov/pubmed/23979942", "http://www.ncbi.nlm.nih.gov/pubmed/15737203", "http://www.ncbi.nlm.nih.gov/pubmed/18693275" ], "ideal_answer": [ "Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract." ], "exact_answer": [ "epithelial cells" ], "type": "factoid", "id": "571ce13f7de986d80d000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18693275", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1382, "text": "These results indicate that the mouse Gsdma and Gsdma3 genes share common function to regulate epithelial maintenance ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23979942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Gasdermin (GSDM or GSDMA), expressed in the upper gastrointestinal tract but frequently silenced in gastric cancers (GCs), regulates apoptosis of the gastric epithelium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19051310", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1294, "text": ". Immunohistochemical analysis revealed that gasdermins are expressed specifically in cells at advanced stages of differentiation in the upper epidermis, the differentiating inner root sheath and hair shaft and in the most mature sebocytes of the sebaceous gland and preputial, meibomium, ceruminous gland, and anal glands. This expression pattern suggests a role for gasdermins in differentiation of the epidermis and its appendages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15737203", "endSection": "abstract" } ] }, { "body": "Where in a protein can a signal sequence be found?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8077949", "http://www.ncbi.nlm.nih.gov/pubmed/12551941", "http://www.ncbi.nlm.nih.gov/pubmed/9624150", "http://www.ncbi.nlm.nih.gov/pubmed/8307567", "http://www.ncbi.nlm.nih.gov/pubmed/8955395", "http://www.ncbi.nlm.nih.gov/pubmed/21834515", "http://www.ncbi.nlm.nih.gov/pubmed/18931123", "http://www.ncbi.nlm.nih.gov/pubmed/21572038", "http://www.ncbi.nlm.nih.gov/pubmed/9013954", "http://www.ncbi.nlm.nih.gov/pubmed/19453274", "http://www.ncbi.nlm.nih.gov/pubmed/9551364", "http://www.ncbi.nlm.nih.gov/pubmed/11231276", "http://www.ncbi.nlm.nih.gov/pubmed/11575719" ], "ideal_answer": [ "Proteins have signal sequences typically resent at the most N-terminal end." ], "exact_answer": [ "N-terminally" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021382" ], "type": "factoid", "id": "550718e9fd1abe1741000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "A transmembrane domain (TMD) at the N-terminus of a membrane protein is a signal sequence that targets the protein to the endoplasmic reticulum (ER) membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21834515", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 384, "text": " an N-terminal signal sequence,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21572038", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 916, "text": "soluble AMO possesses an N-terminal signal sequence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19453274", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 669, "text": "n N-terminal \"twin arginine\" signal sequence suggested ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18931123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Proteins destined for the mitochondrial matrix space have leader sequences that are typically present at the most N-terminal end of the nuclear-encoded precursor protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12551941", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 60, "text": "N-terminal signal sequence ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11575719", "endSection": "title" }, { "offsetInBeginSection": 884, "offsetInEndSection": 957, "text": "The predicted amino-acid sequence includes an N-terminal signal sequence ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11231276", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 560, "text": "These N-terminal sequences lack a typical signal sequence ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9624150", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 448, "text": " TAP can be bypassed by targeting peptides directly to the endoplasmic reticulum (ER) using NH2-terminal signal sequences. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9551364", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 415, "text": "The amino terminal signal sequence, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9013954", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 615, "text": "An amino-terminal domain containing a signal sequence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8955395", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 340, "text": "A nuclear localization signal (NLS) sequence was previously defined by point mutations in three short adjacent clusters of basic amino acids located in the amino-terminal region of the E1 protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8077949", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 688, "text": "he human homologue also contains a putative N-terminal signal sequence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8307567", "endSection": "abstract" } ] }, { "body": "Can FOXOs modulate longevity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20874444", "http://www.ncbi.nlm.nih.gov/pubmed/22438832", "http://www.ncbi.nlm.nih.gov/pubmed/18208360", "http://www.ncbi.nlm.nih.gov/pubmed/21076489", "http://www.ncbi.nlm.nih.gov/pubmed/15942449", "http://www.ncbi.nlm.nih.gov/pubmed/20592766", "http://www.ncbi.nlm.nih.gov/pubmed/19408108", "http://www.ncbi.nlm.nih.gov/pubmed/21431325", "http://www.ncbi.nlm.nih.gov/pubmed/15126506", "http://www.ncbi.nlm.nih.gov/pubmed/19861158", "http://www.ncbi.nlm.nih.gov/pubmed/18371346", "http://www.ncbi.nlm.nih.gov/pubmed/21114762", "http://www.ncbi.nlm.nih.gov/pubmed/22187289", "http://www.ncbi.nlm.nih.gov/pubmed/19066462", "http://www.ncbi.nlm.nih.gov/pubmed/18193389" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B4MB78", "o": "http://linkedlifedata.com/resource/#_42344D42373800B" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42344D42373800B", "o": "GJ14344" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42344D42373800A", "o": "Forkhead box protein O" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42344D42373800B", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B4PTD3", "o": "http://linkedlifedata.com/resource/#_42345054443300D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42345054443300C", "o": "Forkhead 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"http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423350304B3600C", "o": "Forkhead box protein O" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_423350304B3600D", "o": "GG16833" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_423350304B3600D", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B4KBF6", "o": "http://linkedlifedata.com/resource/#_42344B42463600B" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42344B42463600B", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42344B42463600B", "o": "GI21984" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42344B42463600A", "o": "Forkhead box protein O" }, { "p": "http://purl.uniprot.org/core/encodedBy", 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"http://linkedlifedata.com/resource/#_42344A53433200B", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B4G4S8", "o": "http://linkedlifedata.com/resource/#_42344734533800E" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42344734533800E", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42344734533800E", "o": "GL24235" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42344734533800D", "o": "Forkhead box protein O" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A3832745", "o": "C477334" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1311653", "o": "http://linkedlifedata.com/resource/umls/label/A3832745" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3832745", "o": "FOXO protein, Drosophila" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1311653", "o": "http://linkedlifedata.com/resource/umls/label/A3832745" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3832745", "o": "MeSH" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B3LYS5", "o": "http://linkedlifedata.com/resource/#_42334C59533500D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42334C59533500C", "o": "Forkhead box protein O" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42334C59533500D", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42334C59533500D", "o": "GF16233" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B4NFR1", "o": "http://linkedlifedata.com/resource/#_42344E46523100B" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42344E46523100B", "o": "foxo" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42344E46523100A", "o": "Forkhead box protein O" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_42344E46523100B", "o": "GK22687" } ], "ideal_answer": [ "FOXOs are reliable markers of longevity." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/FOXO_DROME", "http://www.uniprot.org/uniprot/FOXO_DROSE", "http://www.uniprot.org/uniprot/FOXO_DROPE", "http://www.uniprot.org/uniprot/FOXO_DROMO", "http://www.uniprot.org/uniprot/FOXO_CAEEL", "http://www.uniprot.org/uniprot/FOXO_DROPS", "http://www.uniprot.org/uniprot/FOXO_DROGR", "http://www.uniprot.org/uniprot/FOXO_DROYA", "http://www.uniprot.org/uniprot/FOXO_DROWI", "http://www.uniprot.org/uniprot/FOXO_DROER", "http://www.uniprot.org/uniprot/FOXO_DROVI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008136", "http://www.uniprot.org/uniprot/FOXO_DROAN" ], "type": "yesno", "id": "52b2ec944003448f55000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438832", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1641, "text": "In contrast to FoxO1, FoxO3a and FoxO6 were specifically diminished in the CNS of HFD animals possibly contributing to the reduced lifespan observed in these animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22187289", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1291, "text": "Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431325", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 437, "text": "Components of anti-ageing and autophagy include SirTs and FoxOs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21114762", "endSection": "abstract" }, { "offsetInBeginSection": 1659, "offsetInEndSection": 1959, "text": "Since Sirts and FoxOs are reliable markers of longevity, the results appear to suggest that Longevinex induces longevity after prolonged feeding via induction of autophagy, while it converts death signals into survival signals and provides cardioprotection within a relatively shorter period of time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21076489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Forkhead box O (FOXO) transcription factors are involved in various cellular processes, including cell proliferation, stress resistance, metabolism, and longevity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20874444", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 595, "text": "In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as exciting prospects for multiple disorders. These transcription factors govern development, proliferation, survival and longevity during multiple cellular environments that can involve oxidative stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592766", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1160, "text": "Here we discuss the fascinating but complex role of FoxOs during cellular injury and oxidative stress, progenitor cell development, fertility, angiogenesis, cardiovascular function, cellular metabolism and diabetes, cell longevity, immune surveillance and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592766", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 896, "text": "Many longevity genes, e.g. FoxOs and SIRT1, are inhibitors of NF-kappaB signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19861158", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1126, "text": "Interestingly, several longevity genes such as SIRT1, SIRT6, and FoxOs can clearly suppress NF-kappaB signaling and in this way delay the aging process and extend lifespan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19408108", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 772, "text": "Yet, FoxOs also can significantly affect normal cell survival and longevity, requiring new treatments for neoplastic growth to modulate novel pathways that integrate cell proliferation, metabolism, inflammation and survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19066462", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 897, "text": "These observations link FoxO function in mammalian systems with the evolutionarily conserved role of FoxO in promotion of stress resistance and longevity in lower phylogenetic systems. Furthermore, these findings have implications for aging in higher organisms and in malignant stem cell biology, and suggest that FoxOs may play an important role in the maintenance and integrity of stem cell compartments in a broad spectrum of tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18208360", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 872, "text": "This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18208360", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 957, "text": "In this review, we focus on the several interactions of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-kappaB signaling pathways. We provide evidence that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-kappaB signaling and simultaneously protect against inflamm-aging process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18193389", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 846, "text": "In diverse species transcription factors belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have been found to be crucial in downstream suppression of the life-shortening effects of insulin/insulin-like growth factor-I receptor signalling pathways that, when upregulated, accelerate ageing by suppression of FOXO. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15942449", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1293, "text": "In humans, FOXO3a, as well as FOXO1 and -4, and their downstream effectors, could hold the key to counteracting ageing and common diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15942449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "FOXO transcription factors have important roles in metabolism, cellular proliferation, stress tolerance, and aging. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15126506", "endSection": "abstract" } ] }, { "body": "Which antibody is implicated in the Bickerstaff's brainstem encephalitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22698187", "http://www.ncbi.nlm.nih.gov/pubmed/18717185", "http://www.ncbi.nlm.nih.gov/pubmed/25379047", "http://www.ncbi.nlm.nih.gov/pubmed/24853856", "http://www.ncbi.nlm.nih.gov/pubmed/16844234", "http://www.ncbi.nlm.nih.gov/pubmed/8194267", "http://www.ncbi.nlm.nih.gov/pubmed/18678825", "http://www.ncbi.nlm.nih.gov/pubmed/23275783", "http://www.ncbi.nlm.nih.gov/pubmed/22984203", "http://www.ncbi.nlm.nih.gov/pubmed/16948943", "http://www.ncbi.nlm.nih.gov/pubmed/16099076", "http://www.ncbi.nlm.nih.gov/pubmed/19664367", "http://www.ncbi.nlm.nih.gov/pubmed/12451613", "http://www.ncbi.nlm.nih.gov/pubmed/11002482", "http://www.ncbi.nlm.nih.gov/pubmed/11442445", "http://www.ncbi.nlm.nih.gov/pubmed/21631649", "http://www.ncbi.nlm.nih.gov/pubmed/18406474", "http://www.ncbi.nlm.nih.gov/pubmed/23927937" ], "ideal_answer": [ "The syndrome defined by Bickerstaff of progressive, external ophthalmoplegia and ataxia, with disturbance of consciousness or hyperreflexia, has subsequently been associated with antiganglioside antibody, anti-GQ1b" ], "exact_answer": [ "antiganglioside antibody" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004660", "http://www.disease-ontology.org/api/metadata/DOID:9588" ], "type": "factoid", "id": "56c1f039ef6e394741000052", "snippets": [ { "offsetInBeginSection": 140, "offsetInEndSection": 406, "text": "In addition, BBE and Fisher syndrome, which are clinically similar and are both associated with the presence of the immunoglobulin G anti-GQ1b antibody, represent a specific autoimmune disease with a wide spectrum of symptoms that include ophthalmoplegia and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25379047", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 503, "text": "The syndrome defined by Bickerstaff of progressive, external ophthalmoplegia and ataxia, with disturbance of consciousness or hyperreflexia, has subsequently been associated with anti-GQ1b antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23927937", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 386, "text": "An anti-GQ1b antibody syndrome has been proposed to underlie the common pathophysiology for the three disorders; however, other studies have found a positive anti-GM1 instead of anti-GQ1b antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22698187", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 951, "text": "Serologic analysis of antibodies against ganglioside complexes (anti-GDIa, anti-GDIb, anti-GM1, anti-GM2, anti-GM3, anti-GQIb and anti-GTIb antibodies) showed negative results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22698187", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1299, "text": "However, contrary to a proposed anti-GQ1b antibody syndrome, we would suggest that pathogenesis of this clinical spectrum is not limited to anti-ganglioside antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22698187", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 1073, "text": "Although there are usually no abnormalities in MFS by routine neuroimaging, in a few cases, contrast enhancement of nerve roots and signs of central nervous system involvement were described supporting the hypothesis of an anti-GQ1b-syndrome, a continuum involving GBS, MFS, and Bickerstaff's brainstem encephalitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21631649", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 785, "text": "Anti-GM1 IgG, GD1a IgG, GQ1b IgG, and GT1a IgG antibodies were positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23275783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "The discovery of the association of the anti-GQ1b IgG antibody with the postinfectious clinical syndromes of ophthalmoplegia, ataxia, and areflexia helped house the phenotypes of the Miller Fisher syndrome (MFS), atypical MFS, Guillain-Barr\u00e9 syndrome with ophthalmoplegia, and Bickerstaff's brainstem encephalitis under one roof. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19664367", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 849, "text": "These findings suggest that host susceptibility may play a role in inducing the production of anti-ganglioside antibodies and the development of Bickerstaff's brainstem encephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18406474", "endSection": "abstract" }, { "offsetInBeginSection": 1541, "offsetInEndSection": 1825, "text": "These antibodies should provide useful serological markers for identifying patients who have atypical GBS with preserved deep tendon reflexes, ataxic GBS, Bickerstaff's brainstem encephalitis or acute ophthalmoparesis, especially for those who have no antibodies to GM1, GD1a or GQ1b.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16844234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22984203", "endSection": "title" }, { "offsetInBeginSection": 201, "offsetInEndSection": 315, "text": "Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18406474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Overlapping Guillain-Barr\u00e9 syndrome and Bickerstaff's brainstem encephalitis associated with anti-GQ1b IgG antibody after herpes simplex virus infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11442445", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Bickerstaff's brainstem encephalitis, Miller Fisher syndrome and Guillain-Barr\u00e9 syndrome overlap in an asthma patient with negative anti-ganglioside antibodies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22698187", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Bickerstaff brainstem encephalitis is a clinical syndrome of ophthalmoplegia, cerebellar ataxia, and central nervous system signs and is associated with the presence of anti-GQ1b antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16948943", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1048, "text": "This is only the second case in the literature of Bickerstaff brainstem encephalitis with raised titers of anti-GQ1b antibodies described in association with M pneumoniae infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16948943", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1372, "text": "Of those patients with Fisher syndrome, Bickerstaff's brainstem encephalitis, ataxic GBS or acute ophthalmoparesis, 33% of 67 anti-GM1b-positive, and 52% of 25 anti-GalNAc-GD1a-positive patients had no anti-GQ1b antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16844234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Fisher syndrome or Bickerstaff brainstem encephalitis? Anti-GQ1b IgG antibody syndrome involving both the peripheral and central nervous systems.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12451613", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barr\u00e9 syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18678825", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1371, "text": "This case presented clinical characteristics of three syndromes concurrently-Fisher syndrome, Bickerstaff brainstem encephalitis, and Guillain-Barr\u00e9 syndrome-that may be collectively called 'anti-GQ1b IgG antibody syndrome'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18717185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "This is the case of a 79-year-old man with chronic lymphocytic leukemia who presented with Guillain-Barr\u00e9 syndrome with features overlapping with the Miller Fisher syndrome and Bickerstaff brainstem encephalitis and positive antiganglioside GQ1b antibody about 6 months after treatment with bendamustine and rituximab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24853856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22984203", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "[A case report of Bickerstaff's brainstem encephalitis with positive anti GQ 1 b, GT 1 a, GM 1 ganglioside antibodies].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11002482", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "[Probable Bickerstaff's brainstem encephalitis associated with anti-GQ1b antibody].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8194267", "endSection": "title" }, { "offsetInBeginSection": 88, "offsetInEndSection": 203, "text": "Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18406474", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 577, "text": "Nevertheless, 66% of patients with Bickerstaff syndrome have anti-GQ1b antibody during the acute phase period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16099076", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 203, "text": "Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18406474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Overlapping Guillain-Barr\u00e9 syndrome and Bickerstaff's brainstem encephalitis associated with anti-GQ1b IgG antibody after herpes simplex virus infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11442445", "endSection": "title" } ] }, { "body": "Which micro-RNAs have been associated in the pathogenesis of Rheumatoid Arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20840794", "http://www.ncbi.nlm.nih.gov/pubmed/18383392", "http://www.ncbi.nlm.nih.gov/pubmed/21611196", "http://www.ncbi.nlm.nih.gov/pubmed/23649045", "http://www.ncbi.nlm.nih.gov/pubmed/21600203", "http://www.ncbi.nlm.nih.gov/pubmed/18759964", "http://www.ncbi.nlm.nih.gov/pubmed/22161761", "http://www.ncbi.nlm.nih.gov/pubmed/22903258", "http://www.ncbi.nlm.nih.gov/pubmed/21339228", "http://www.ncbi.nlm.nih.gov/pubmed/22823586", "http://www.ncbi.nlm.nih.gov/pubmed/21339227", "http://www.ncbi.nlm.nih.gov/pubmed/19404929", "http://www.ncbi.nlm.nih.gov/pubmed/20459811", "http://www.ncbi.nlm.nih.gov/pubmed/24283221", "http://www.ncbi.nlm.nih.gov/pubmed/21279994", "http://www.ncbi.nlm.nih.gov/pubmed/19931339", "http://www.ncbi.nlm.nih.gov/pubmed/24120842", "http://www.ncbi.nlm.nih.gov/pubmed/23318734", "http://www.ncbi.nlm.nih.gov/pubmed/21416408", "http://www.ncbi.nlm.nih.gov/pubmed/18438844", "http://www.ncbi.nlm.nih.gov/pubmed/22100329", "http://www.ncbi.nlm.nih.gov/pubmed/23280137", "http://www.ncbi.nlm.nih.gov/pubmed/23385088", "http://www.ncbi.nlm.nih.gov/pubmed/20223711", "http://www.ncbi.nlm.nih.gov/pubmed/20870441", "http://www.ncbi.nlm.nih.gov/pubmed/20864373", "http://www.ncbi.nlm.nih.gov/pubmed/21354921", "http://www.ncbi.nlm.nih.gov/pubmed/22494429", "http://www.ncbi.nlm.nih.gov/pubmed/23138379", "http://www.ncbi.nlm.nih.gov/pubmed/22562984" ], "ideal_answer": [ "Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients." ], "exact_answer": [ [ "miR-155" ], [ "miR-146a" ], [ "miR-124a" ], [ "miR-222" ], [ "miR-223" ], [ "miR-203" ], [ "miR-346" ], [ "miR-132" ], [ "miR-363" ], [ "miR-498" ], [ "miR-15a" ], [ "miR-16" ], [ "miR-18a" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009405", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "list", "id": "533c3533c45e133714000004", "snippets": [ { "offsetInBeginSection": 1447, "offsetInEndSection": 1548, "text": "This study provides the first description of increased expression of miRNA miR-155 and miR-146a in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18383392", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 275, "text": "In this study we investigated the expression, regulation, and function of miR-155 and miR-146a in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) and RA synovial tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18383392", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 355, "text": "The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in synovial tissue from patients with rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18438844", "endSection": "abstract" }, { "offsetInBeginSection": 1478, "offsetInEndSection": 1619, "text": "This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFalpha and IL-1beta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18438844", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 104, "text": "pregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759964", "endSection": "title" }, { "offsetInBeginSection": 426, "offsetInEndSection": 707, "text": "Total RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759964", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 977, "text": "Rheumatoid arthritis peripheral blood mononuclear cells exhibited between 1.8-fold and 2.6-fold increases in miR-146a, miR-155, miR-132, and miR-16 expression, whereas let-7a expression was not significantly different compared with healthy control individuals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759964", "endSection": "abstract" }, { "offsetInBeginSection": 2106, "offsetInEndSection": 2371, "text": "Our data also suggest a possible mechanism contributing to rheumatoid arthritis pathogenesis, whereby miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-alpha production in patients with rheumatoid arthritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759964", "endSection": "abstract" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1540, "text": "Repression of TRAF6 and/or IRAK-1 in THP-1 cells resulted in up to an 86% reduction in tumor necrosis factor-alpha production, implicating that normal miR-146a function is critical for the regulation of tumor necrosis factor-alpha production", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18759964", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 170, "text": "icroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404929", "endSection": "title" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1156, "text": "We found that miR-124a levels significantly decreased in RA synoviocytes as compared with OA synoviocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404929", "endSection": "abstract" }, { "offsetInBeginSection": 1485, "offsetInEndSection": 1597, "text": "Induction of miR-124a in RA synoviocytes significantly suppressed the production of the CDK-2 and MCP-1 proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404929", "endSection": "abstract" }, { "offsetInBeginSection": 1774, "offsetInEndSection": 1903, "text": "he results of this study suggest that miR-124a is a key miRNA in the posttranscriptional regulatory mechanisms of RA synoviocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404929", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 87, "text": "iR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19931339", "endSection": "title" }, { "offsetInBeginSection": 286, "offsetInEndSection": 627, "text": "Although a multifactorial pathogenesis has been hypothesized, the precise mechanisms leading to the disease are still poorly understood at the molecular level. miRNA expression profile analysis highlighted that miR-223 is the only miRNA that is strikingly deregulated in peripheral T-lymphocytes from RA patients compared with healthy donors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19931339", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1275, "text": "In summary, our data provide a first characterization of the miRNA expression profiles of peripheral T-lymphocytes of RA patients, identifying miR-223 as overexpressed in CD4(+) naive T-lymphocytes from these individuals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19931339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459811", "endSection": "title" }, { "offsetInBeginSection": 594, "offsetInEndSection": 692, "text": "The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459811", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1763, "text": "We have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-alpha levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459811", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 92, "text": "icroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840794", "endSection": "title" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1059, "text": "Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840794", "endSection": "abstract" }, { "offsetInBeginSection": 1487, "offsetInEndSection": 1601, "text": "These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840794", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 163, "text": "polymorphism in the 3'-UTR of interleukin-1 receptor-associated kinase (IRAK1), a target gene of miR-146a, is associated with rheumatoid arthritis susceptibility", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870441", "endSection": "title" }, { "offsetInBeginSection": 263, "offsetInEndSection": 374, "text": "MicroRNA-146a was found to be increased in synovial fibroblasts, synovial tissue and PBMC from patients with RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870441", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1134, "text": "This is the first study that addresses association of a variant in a target of miR-146a, IRAK1 gene, with RA susceptibility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870441", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 117, "text": "ltered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279994", "endSection": "title" }, { "offsetInBeginSection": 115, "offsetInEndSection": 335, "text": "Previously, we described increased expression of miR-155 and miR-146a in rheumatoid arthritis (RA) and showed a repressive effect of miR-155 on matrix metalloproteinase (MMP) expression in RA synovial fibroblasts (RASFs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279994", "endSection": "abstract" }, { "offsetInBeginSection": 1575, "offsetInEndSection": 1670, "text": "The current results demonstrate methylation-dependent regulation of miR-203 expression in RASFs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279994", "endSection": "abstract" }, { "offsetInBeginSection": 1671, "offsetInEndSection": 1879, "text": " Importantly, they also show that elevated levels of miR-203 lead to increased secretion of MMP-1 and IL-6 via the NF-\u03baB pathway and thereby contribute to the activated phenotype of synovial fibroblasts in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279994", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 120, "text": "iR-124a as a key regulator of proliferation and MCP-1 secretion in synoviocytes from patients with rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21339227", "endSection": "title" }, { "offsetInBeginSection": 364, "offsetInEndSection": 498, "text": "Transfection of miR-124a into RA synoviocytes significantly suppressed their proliferation and arrested the cell cycle at the G1 phase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21339227", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 911, "text": "It is proposed that miR-124a is a key miRNA in the post-transcriptional regulatory mechanisms of RA synoviocytes, and has a therapeutic potential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21339227", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 156, "text": "Expression of miR-146a and miR-16 in peripheral blood mononuclear cells of patients with rheumatoid arthritis and their correlation to the disease activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21354921", "endSection": "title" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1128, "text": "The elevated expression levels of miR-146a and miR-16 are correlated to RA disease activity, suggesting their value in assessment of the clinical disease activity of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21354921", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 125, "text": "iR-346 controls release of TNF-\u03b1 protein and stability of its mRNA in rheumatoid arthritis via tristetraprolin stabilization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21611196", "endSection": "title" }, { "offsetInBeginSection": 426, "offsetInEndSection": 650, "text": "Using a microarray, we found two miRNAs, miR-125b and miR-939 predicted to target the 3'-UTR of TNF-\u03b1 mRNA, to be up-regulated in RA FLS in response to LPS, but their repression did not restore mature TNF-\u03b1 expression in FLS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21611196", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 781, "text": "We showed previously that miR-346, which is upregulated in LPS-activated FLS, inhibited Btk expression that stabilized TNF-\u03b1 mRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21611196", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 555, "text": "Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100329", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 107, "text": "own-regulation of microRNA-34a* in rheumatoid arthritis synovial fibroblasts promotes apoptosis resistance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22161761", "endSection": "title" }, { "offsetInBeginSection": 848, "offsetInEndSection": 1055, "text": "Basal expression levels of miR-34a* were found to be reduced in synovial fibroblasts from RA patients compared to osteoarthritis patients, whereas levels of miR-34a, miR-34b/b*, and miR-34c/c* did not differ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22161761", "endSection": "abstract" }, { "offsetInBeginSection": 1623, "offsetInEndSection": 1724, "text": "Our data provide evidence of a methylation-specific down-regulation of proapoptotic miR-34a* in RASFs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22161761", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 170, "text": "dentification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562984", "endSection": "title" }, { "offsetInBeginSection": 720, "offsetInEndSection": 867, "text": "miR-seq demonstrated that TghuTNF-SF exhibit a distinct pathogenic profile with 22 significantly upregulated and 30 significantly downregulated miR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562984", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1063, "text": "Validation assays confirmed the dysregulation of miR-223, miR-146a and miR-155 previously associated with human rheumatoid arthritis (RA) pathology, as well as that of miR-221/222 and miR-323-3p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562984", "endSection": "abstract" }, { "offsetInBeginSection": 1594, "offsetInEndSection": 1678, "text": "the authors identified miR-221/222 and miR-323-3p as novel dysregulated miR in RA SF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22562984", "endSection": "abstract" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1633, "text": "Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22823586", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 144, "text": "iR-146a polymorphism is associated with asthma but not with systemic lupus erythematosus and juvenile rheumatoid arthritis in Mexican patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22823586", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 99, "text": "verexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903258", "endSection": "title" }, { "offsetInBeginSection": 80, "offsetInEndSection": 159, "text": "MicroRNA-223 (miR-223) is reported to play critical roles in osteoclastogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903258", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1589, "text": "MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903258", "endSection": "abstract" }, { "offsetInBeginSection": 1591, "offsetInEndSection": 1700, "text": "This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903258", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1085, "text": "MiR-223 was more highly expressed in RA synovium than in osteoarthritis (OA) synovium due to the increased number of miR-223-positive cells in RA synovium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903258", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 124, "text": "ssociation of pre-miRNA-146a rs2910164 and pre\u2011miRNA-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23138379", "endSection": "title" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1439, "text": "Our findings demonstrated that the hsa-mir-499 rs3746444, but not mir-146a rs2910164, polymorphism is associated with an increased RA risk in a sample of the Iranian population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23138379", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 139, "text": "umor necrosis factor \u03b1-induced microRNA-18a activates rheumatoid arthritis synovial fibroblasts through a feedback loop in NF-\u03baB signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23280137", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 161, "text": "To elucidate whether the microRNA (miRNA) cluster miR-17-92 contributes to the activated phenotype of rheumatoid arthritis synovial fibroblasts (RASFs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23280137", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 895, "text": "We found that TNF\u03b1 induces the expression of miR-17-92 in RASFs in an NF-\u03baB-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23280137", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1270, "text": "Using reporter gene assays, we identified the NF-\u03baB pathway inhibitor TNF\u03b1-induced protein 3 as a new target of miR-18a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23280137", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1708, "text": "Our data suggest that the miR-17-92-derived miR-18a contributes to cartilage destruction and chronic inflammation in the joint through a positive feedback loop in NF-\u03baB signaling, with concomitant up-regulation of matrix-degrading enzymes and mediators of inflammation in RASFs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23280137", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 774, "text": "As inflammation and joint damage are the main hallmarks of RA, we focused on the three miRNAs, miR-146a, miR-155 and miR-223, whose functions have been studied in both the processes and the pathogenic role investigated in the experimental models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318734", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 979, "text": "Focusing on the role of miR-146a, miR-155 and miR-223 in RA pathogenesis emphasizes the intertwined relationships between bone homeostasis and immunity, and the prominent role of monocytes in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318734", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 619, "text": "In a final perspective section we discuss the potential impact of therapeutic miR-155 modulation in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23649045", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 151, "text": "correlation between whole blood and PBMC expression levels of miR-155 and miR-146a in healthy controls and rheumatoid arthritis patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24120842", "endSection": "title" }, { "offsetInBeginSection": 654, "offsetInEndSection": 821, "text": "We demonstrated a highly significant linear correlation between miR-146a and miR-155 expression in PBMC and whole blood, from both healthy individuals and RA patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24120842", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 183, "text": "expression of specific microRNAs (miRNA) in peripheral blood-derived mononuclear cells (PBMC), particularly miR-146a and miR-155, is associated with rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24120842", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 106, "text": "icroRNA-323-3p with clinical potential in rheumatoid arthritis, Alzheimer's disease and ectopic pregnancy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24283221", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 491, "text": "It has been shown that miR-323-3p associates with the pathogenesis of several diseases, such as rheumatoid arthritis, Alzheimer's disease and ectopic pregnancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24283221", "endSection": "abstract" } ] }, { "body": "Is there an association between FGFR3 mutation and plagiocephaly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23949953", "http://www.ncbi.nlm.nih.gov/pubmed/17992550", "http://www.ncbi.nlm.nih.gov/pubmed/17693524", "http://www.ncbi.nlm.nih.gov/pubmed/21739570", "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "http://www.ncbi.nlm.nih.gov/pubmed/14577033", "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "http://www.ncbi.nlm.nih.gov/pubmed/15253176", "http://www.ncbi.nlm.nih.gov/pubmed/18216705" ], "ideal_answer": [ "Yes, FGFR3 mutation is associated with plagiocephaly. It is the most common mutation in plagiocephaly. FGFR genes have important effects on bone development, and mutations in 4 \"hot spot\" exons of FGFR1-3 are found in many patients with craniosynostosis and some with synostotic plagiocephaly." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/FGFR3_CHICK", "http://www.uniprot.org/uniprot/FGFR3_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049068", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/FGFR3_PLEWA", "http://www.uniprot.org/uniprot/FGFR3_DANRE", "http://www.uniprot.org/uniprot/FGFR3_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059041" ], "type": "yesno", "id": "56c1f042ef6e394741000056", "snippets": [ { "offsetInBeginSection": 251, "offsetInEndSection": 490, "text": "Series of neurosurgical interventions were carried out, principally for acrocephaly and posterior plagiocephaly. The most common achondroplasia mutation, a p.Gly380Arg in the fibroblast growth factor receptor 3 (FGFR3) gene, was detected. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23949953", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 335, "text": " The most common mutation for achondroplasia (FGFR3 Gly380Arg, resulting in 1138G>A) was identified. Imaging studies disclosed complex craniosynostosis and neurosurgical intervention was carried out, particularly for posterior plagiocephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21739570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "FGFR mutations and plagiocephaly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18216705", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "FGFR genes have important effects on bone development, and mutations in 4 \"hot spot\" exons of FGFR1-3 are found in many patients with craniosynostosis and some with synostotic plagiocephaly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18216705", "endSection": "abstract" }, { "offsetInBeginSection": 1667, "offsetInEndSection": 1805, "text": "Mutation analyses in the FGFR3 gene revealed nucleotide alterations located in the mutational hot spot at amino acid residue 250 (g.C749).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17992550", "endSection": "abstract" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1351, "text": "RESULTS: In our cohort of 159 patients with various craniosynostosis syndromes, mutations were found in 100% of patients with Apert syndrome, 83.3% with Pfeiffer syndrome, 72.7% with Crouzon syndrome, 50.0% with Saethre-Chotzen syndrome, 27.7% with plagiocephaly, 31.8% with brachicephaly, 20% of complex cases, and 6.9% of mixed cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17693524", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 253, "text": "The genetic alterations that could cause unilateral coronal synostosis are more elusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15253176", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1356, "text": "Mutations were found in eight of 47 patients: two patients with different single-amino-acid changes in FGFR2, three patients with FGFR3 Pro250Arg, and three patients with TWIST mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15253176", "endSection": "abstract" }, { "offsetInBeginSection": 1721, "offsetInEndSection": 1870, "text": "Other abnormalities in the craniofacial region and extremities were clues to a particular mutation in FGFR2, FGFR3, TWIST, or the X-linked mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15253176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1798, "text": "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 851, "text": "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1076, "text": "Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children's Hospital of Philadelphia were evaluated for the FGFR3 mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 930, "text": "Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children's Hospital of Philadelphia were evaluated for the FGFR3 mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "FGFR genes have important effects on bone development, and mutations in 4 "hot spot" exons of FGFR1-3 are found in many patients with craniosynostosis and some with synostotic plagiocephaly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18216705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 713, "text": "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1669, "text": "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 32, "text": "FGFR mutations and plagiocephaly", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18216705", "endSection": "title" }, { "offsetInBeginSection": 759, "offsetInEndSection": 922, "text": "Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children's Hospital of Philadelphia were evaluated for the FGFR3 mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 715, "text": "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1661, "text": "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 430, "text": " To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation. Of 37 patients with unicoronal synostosis, 4 tested positive for the Pro250Arg mutation in FGFR3, and 33 were negative for this mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 823, "text": "In a girl with seemingly isolated plagiocephaly we identified a P250L (749C-->T) mutation in FGFR3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14577033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "FGFR mutations and plagiocephaly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18216705", "endSection": "title" }, { "offsetInBeginSection": 575, "offsetInEndSection": 715, "text": "None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580776", "endSection": "abstract" }, { "offsetInBeginSection": 1510, "offsetInEndSection": 1661, "text": "The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11743367", "endSection": "abstract" } ] }, { "body": "Are CD44 variants (CD44v) associated with poor prognosis of metastasis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7587629", "http://www.ncbi.nlm.nih.gov/pubmed/9732216", "http://www.ncbi.nlm.nih.gov/pubmed/10601048", "http://www.ncbi.nlm.nih.gov/pubmed/12842543", "http://www.ncbi.nlm.nih.gov/pubmed/7585612", "http://www.ncbi.nlm.nih.gov/pubmed/7544777", "http://www.ncbi.nlm.nih.gov/pubmed/9742519", "http://www.ncbi.nlm.nih.gov/pubmed/11751503", "http://www.ncbi.nlm.nih.gov/pubmed/9949626", "http://www.ncbi.nlm.nih.gov/pubmed/12747468", "http://www.ncbi.nlm.nih.gov/pubmed/9815811", "http://www.ncbi.nlm.nih.gov/pubmed/8869105", "http://www.ncbi.nlm.nih.gov/pubmed/9224749", "http://www.ncbi.nlm.nih.gov/pubmed/9849582", "http://www.ncbi.nlm.nih.gov/pubmed/9413216" ], "ideal_answer": [ "Yes, several isoforms (obtained by by usage of ten variant exons in various combinations) have been causally related to metastasis." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009362", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018960", "http://www.uniprot.org/uniprot/CD44_BOVIN" ], "type": "yesno", "id": "533bf29cc45e133714000001", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 41, "text": "CD44 variants and prognosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10601048", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 136, "text": "The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10601048", "endSection": "abstract" }, { "offsetInBeginSection": 1285, "offsetInEndSection": 1417, "text": "Positive CD44v3 expression was associated with more advanced pathological stage and poorer prognosis than negative CD44v3 expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11751503", "endSection": "abstract" }, { "offsetInBeginSection": 1393, "offsetInEndSection": 1518, "text": "CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12747468", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 138, "text": "D44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12747468", "endSection": "title" }, { "offsetInBeginSection": 1661, "offsetInEndSection": 1852, "text": "CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12842543", "endSection": "abstract" }, { "offsetInBeginSection": 2363, "offsetInEndSection": 2497, "text": "analysis of CD44v expression provides indications of biological and clinical relevance also in low grade lymphoproliferative disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9949626", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 107, "text": "clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9949626", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 82, "text": "CD44 variants and its association with survival in pancreatic cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9849582", "endSection": "title" }, { "offsetInBeginSection": 10, "offsetInEndSection": 117, "text": "CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9849582", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1637, "text": "CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9849582", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1508, "text": "CD44v8-10 may play an important role in the adhesion of tumor cells to the capillaries of distant organs in the metastatic process, and that immunohistochemical detection of CD44v8-10 may be a biologic marker of prognostic significance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9742519", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 991, "text": "combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9732216", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 195, "text": "variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9413216", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 112, "text": "expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9815811", "endSection": "title" }, { "offsetInBeginSection": 1409, "offsetInEndSection": 1639, "text": "a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9815811", "endSection": "abstract" }, { "offsetInBeginSection": 1305, "offsetInEndSection": 1397, "text": "Expression of CD44v6 may suggest an increased risk for local lymph node metastasis in NSCLCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9224749", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 926, "text": "different CD44 isoforms are found in human skin cancers and are modulated during carcinogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8869105", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 99, "text": "D44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7585612", "endSection": "title" }, { "offsetInBeginSection": 683, "offsetInEndSection": 851, "text": "Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7585612", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 459, "text": "Certain splice variants (CD44v) can promote the metastatic behaviour of cancer cells. In human colon and breast cancer the presence of epitopes encoded by exon v6 on primary resected tumour material indicates poor prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7587629", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 434, "text": "In human mammary carcinomas and colorectal carcinomas, the expression of CD44v has also been correlated with more progressed tumor stages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7544777", "endSection": "abstract" } ] }, { "body": "Is Bladder training an effective method to treat urge incontinence ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2653554", "http://www.ncbi.nlm.nih.gov/pubmed/8006342", "http://www.ncbi.nlm.nih.gov/pubmed/3704568", "http://www.ncbi.nlm.nih.gov/pubmed/8185987", "http://www.ncbi.nlm.nih.gov/pubmed/12614251", "http://www.ncbi.nlm.nih.gov/pubmed/19174937", "http://www.ncbi.nlm.nih.gov/pubmed/1459383", "http://www.ncbi.nlm.nih.gov/pubmed/6887404", "http://www.ncbi.nlm.nih.gov/pubmed/22453268", "http://www.ncbi.nlm.nih.gov/pubmed/6534448", "http://www.ncbi.nlm.nih.gov/pubmed/3758628", "http://www.ncbi.nlm.nih.gov/pubmed/19281722", "http://www.ncbi.nlm.nih.gov/pubmed/8394146", "http://www.ncbi.nlm.nih.gov/pubmed/20877608", "http://www.ncbi.nlm.nih.gov/pubmed/3765943", "http://www.ncbi.nlm.nih.gov/pubmed/16413359", "http://www.ncbi.nlm.nih.gov/pubmed/20527606", "http://www.ncbi.nlm.nih.gov/pubmed/10198479", "http://www.ncbi.nlm.nih.gov/pubmed/12493360", "http://www.ncbi.nlm.nih.gov/pubmed/8022508" ], "ideal_answer": [ "Yes. Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy. Quoted results vary from 26 to 90% . Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053202", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001745", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001743", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014549" ], "type": "yesno", "id": "515df98f298dcd4e51000030", "snippets": [ { "offsetInBeginSection": 1233, "offsetInEndSection": 1492, "text": "Mindfulness-based stress reduction appears to be a treatment worthy of further study, as in the short term, it is as effective as historical studies of drug treatment and bladder training in reducing urge incontinence and incontinence-related quality of life.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22453268", "endSection": "sections.0" }, { "offsetInBeginSection": 615, "offsetInEndSection": 760, "text": "All patients, irrespective of the results of cystometry were subsequently treated with oxybutynin 2.5 mg twice daily along with bladder training.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20527606", "endSection": "sections.0" }, { "offsetInBeginSection": 1683, "offsetInEndSection": 1930, "text": "Of the 29 patients with stable bladder and symptoms of OAB, 100% cure rate was achieved in 20 (68.9%) and 06 (20.6%) patients respectively. While in 3 patients in both groups, decrease of symptoms upto 75% after 6 months of treatment was observed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20527606", "endSection": "sections.0" }, { "offsetInBeginSection": 2200, "offsetInEndSection": 2301, "text": "Both urodynamically proven unstable and stable bladder showed nearly equal improvement with treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20527606", "endSection": "sections.0" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1777, "text": "There are 3 types of urine incontinence (urge-, stress-, and overflow-incontinence). Another standardization of urinary incontinence follows dysfunctions of the pelvic floor: detrusor muscle-dependent, due to sphincter spasm, prostate gland dependent. Urge incontinence with a dysfunction of the detrusor muscle is the most common type. Mixed types are frequent. Non-drug measures (e.g. pelvic muscle training, bladder training, toilet training are first choice treatments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19281722", "endSection": "sections.0" }, { "offsetInBeginSection": 433, "offsetInEndSection": 686, "text": "Treatment of stress, urge and mixed incontinence can usually be commenced in primary care; pelvic floor exercises and bladder training are preferred. If bladder training is not effective for urge incontinence, anticholinergic drugs should be considered.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19174937", "endSection": "sections.0" }, { "offsetInBeginSection": 322, "offsetInEndSection": 527, "text": "Sixty patients (age 8 to 12 years) with urge incontinence or dysfunctional voiding were evaluated. After a no-treatment control period (average 6 months), patients underwent a 6-day bladder training course", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16413359", "endSection": "sections.0" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1047, "text": "Six months after training completion, 64.1% and 64.7% of the inpatient and outpatient groups with daytime wetting and 51.5% and 17.7% of the inpatient and outpatient groups with nighttime wetting were cured or had improved", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16413359", "endSection": "sections.0" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1236, "text": "Of the inpatient group with urge incontinence, the functional bladder capacity increased by 15%.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16413359", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 150, "text": "To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12614251", "endSection": "sections.0" }, { "offsetInBeginSection": 1789, "offsetInEndSection": 1974, "text": "CONCLUSIONS: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12614251", "endSection": "sections.0" }, { "offsetInBeginSection": 341, "offsetInEndSection": 542, "text": "Bladder training is a modification of bladder drill that is conducted more gradually on an outpatient basis and has resulted in significant reduction of incontinence in older, community-dwelling women.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12493360", "endSection": "sections.0" }, { "offsetInBeginSection": 179, "offsetInEndSection": 365, "text": "OBJECTIVE: To evaluate the long-term effect of treatment of female incontinence by the general practitioner (pelvic floor exercises, and bladder training) in female urinary incontinence.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10198479", "endSection": "sections.0" }, { "offsetInBeginSection": 548, "offsetInEndSection": 769, "text": "Stress incontinence and urge incontinence were treated by means of pelvic floor exercises and bladder training respectively, while a mixed incontinence was treated by bladder training followed by pelvic floor exercises. T", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10198479", "endSection": "sections.0" }, { "offsetInBeginSection": 628, "offsetInEndSection": 746, "text": "The treatment consisted of training of pelvic muscles in stress incontinence and bladder training in urge incontinence", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8022508", "endSection": "sections.0" }, { "offsetInBeginSection": 871, "offsetInEndSection": 993, "text": "RESULTS: After 3 months the mean frequency of urine loss per week diminished from 21 to 8, and after 12 months to 6 times.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8022508", "endSection": "sections.0" }, { "offsetInBeginSection": 117, "offsetInEndSection": 253, "text": "Some elders suffering from urge incontinence prefer pelvic muscle exercises to bladder training as the behavioral intervention of choice", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8006342", "endSection": "sections.0" }, { "offsetInBeginSection": 1561, "offsetInEndSection": 1654, "text": "for eight out of nine women their continence had improved, both subjectively and objectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8185987", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8394146", "endSection": "sections.0" }, { "offsetInBeginSection": 146, "offsetInEndSection": 281, "text": "Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1459383", "endSection": "sections.0" }, { "offsetInBeginSection": 673, "offsetInEndSection": 756, "text": "After 3 months about 60% of the patients were either dry or only mildly incontinent", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1459383", "endSection": "sections.0" }, { "offsetInBeginSection": 829, "offsetInEndSection": 942, "text": "terodiline group shows this drug to be a valuable adjunct to a bladder regimen in children with urge incontinence", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2653554", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 551, "text": "Basing on our experience with 39 patients with severe urge incontinence (in one-quarter of the cases pure urge incontinence, in one-half of the cases mixed incontinence and in a further quarter of the cases neurogenic bladder disorders) a supervised programme (mictiogram) and a well-tried therapy (especially in the Anglo-Saxon countries) consisting of the triad hospitalisation/bladder training/medication therapy are presented. After an average hospitalisation period of 14 days, we were able to achieve a symptom-free state in 94% of the patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3758628", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Anamnestic and urodynamical results are evaluated before and after bladder retraining drill (BRD) in women suffering from urge incontinence.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3765943", "endSection": "sections.0" }, { "offsetInBeginSection": 459, "offsetInEndSection": 561, "text": "We could state that the BRD is a good possibility to realize multistep-therapy of female incontinence.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3765943", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Twenty consecutive female patients with urge incontinence and stable detrusor function on provocative rapid fill CO2-cystometry were treated as out-patients with a bladder training programme and with terodiline/placebo in a double-blind cross-over design.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3704568", "endSection": "sections.0" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1137, "text": "In conclusion, female patients with idiopathic urge incontinence and stable detrusor function did respond to treatment as do female patients with urge incontinence and proven instability.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3704568", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The results of in-patient bladder training in 65 women with frequency, urgency and urge incontinence are reported. There was a good initial response in 88%. By 6 months the response rate had fallen to 38%.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6534448", "endSection": "sections.0" }, { "offsetInBeginSection": 206, "offsetInEndSection": 394, "text": "Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6534448", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Bladder training and/or biofeedback techniques were used to treat 75 patients with frequency, urgency, nocturia and urge incontinence. Significant improvement or cure was obtained in 70 per cent of enuretic children, and 66 per cent of men and 74 per cent of women with unstable detrusor function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6887404", "endSection": "sections.0" } ] }, { "body": "What is the scope of the OMIA database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16381939", "http://www.ncbi.nlm.nih.gov/pubmed/21737319", "http://www.ncbi.nlm.nih.gov/pubmed/22140104", "http://www.ncbi.nlm.nih.gov/pubmed/18940862", "http://www.ncbi.nlm.nih.gov/pubmed/21982513", "http://www.ncbi.nlm.nih.gov/pubmed/17170002", "http://www.ncbi.nlm.nih.gov/pubmed/21097890" ], "ideal_answer": [ "Online Mendelian Inheritance in Animals (OMIA) is a comprehensive, annotated catalogue of inherited disorders and other familial traits in animals. OMIA is a comprehensive resource of phenotypic information on heritable animal traits and genes in a strongly comparative context, relating traits to genes where possible." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ], "type": "summary", "id": "56b77a866e3f8eaf4c000004", "snippets": [ { "offsetInBeginSection": 769, "offsetInEndSection": 816, "text": "Online Mendelian Inheritance in Animals (OMIA),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22140104", "endSection": "abstract" }, { "offsetInBeginSection": 1113, "offsetInEndSection": 1159, "text": "Online Mendelian Inheritance in Animals (OMIA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21982513", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 445, "text": "nline Mendelian Inheritance in Animals (OMIA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737319", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 925, "text": "Online Mendelian Inheritance in Animals (OMIA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097890", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 874, "text": "Online Mendelian Inheritance in Animals (OMIA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18940862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Online Mendelian Inheritance in Animals (OMIA) is a comprehensive, annotated catalogue of inherited disorders and other familial traits in animals other than humans and mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381939", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 393, "text": "Structured as a comparative biology resource, OMIA is a comprehensive resource of phenotypic information on heritable animal traits and genes in a strongly comparative context, relating traits to genes where possible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381939", "endSection": "abstract" } ] }, { "body": "What is the effect of methotrexate in treating uveitis due to juvenile idiopathic arthritis ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17706583", "http://www.ncbi.nlm.nih.gov/pubmed/19707402", "http://www.ncbi.nlm.nih.gov/pubmed/17932849", "http://www.ncbi.nlm.nih.gov/pubmed/22034564", "http://www.ncbi.nlm.nih.gov/pubmed/15693100", "http://www.ncbi.nlm.nih.gov/pubmed/22859354", "http://www.ncbi.nlm.nih.gov/pubmed/21145533", "http://www.ncbi.nlm.nih.gov/pubmed/18949668" ], "ideal_answer": [ "The first-line standard therapy for uveitis is topical and systemic corticosteroids, often reinforced by methotrexate as a second-line disease-modifying antirheumatic drug (DMARD). MTX has a topical steroid sparing effect as well. Early treatment with MTX is advocated to prevent complications such as cataract. There are no trial data on the effect of MTX. Most experience among DMARD's/ immunosuppressive drugs has been obtained with methotrexate (MTX) in juvenile idiopathic arthritis. However, controlled studies in uveitis are still missing, so that treatment with MTX and all other immunosuppressive drugs (ciclosporine A, azathioprine, mycophenolate mofetil) only reaches an evidence level III (expert opinion, clinical experience or descriptive study). Biologic DMARDs can be used with Methotrexate in refractory uveitis as well." ], "type": "summary", "id": "515de127298dcd4e51000020", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 215, "text": "To characterize disease-modifying antirheumatic drug (DMARD) use for children with juvenile idiopathic arthritis (JIA) in the United States and to determine patient factors associated with medication use.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859354", "endSection": "sections.0" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1088, "text": "Among children without systemic arthritis, methotrexate use was most strongly associated with uveitis (OR 5.2, 95% CI 3.6-7.6), anticitrullinated protein antibodies (OR 4.5, 95% CI 1.7-12), and extended oligoarthritis (OR 4.1, 95% CI 2.5-6.6)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859354", "endSection": "sections.0" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1824, "text": "About three-quarters of all children with JIA in the CARRA Registry received nonbiologic DMARD. Nearly one-half received biologic DMARD, and their use was strongly associated with RF-positive polyarthritis, PsA, uveitis, and systemic arthritis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22859354", "endSection": "sections.0" }, { "offsetInBeginSection": 227, "offsetInEndSection": 300, "text": "pediatric JIA patients who were being treated with MTX for active uveitis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21145533", "endSection": "sections.0" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1170, "text": "Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21145533", "endSection": "sections.0" }, { "offsetInBeginSection": 370, "offsetInEndSection": 771, "text": "Most experience among DMARD's/ immunosuppressive drugs has been obtained with methotrexate (MTX) in juvenile idiopathic arthritis. However, controlled studies in uveitis are still missing, so that treatment with MTX and all other immunosuppressive drugs (ciclosporine A, azathioprine, mycophenolate mofetil) only reaches an evidence level III (expert opinion, clinical experience or descriptive study)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18949668", "endSection": "sections.0" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1463, "text": "The data suggest that MTX is very effective in controlling inflammation of uveitis in patients with JIA. However, additional topical steroids or systemic immunosuppressive drugs are often required.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932849", "endSection": "sections.0" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1552, "text": "The risk factor for development of early cataract requiring surgery in children with JIA-associated uveitis is the presence of posterior synechia at the time of diagnosis of uveitis. However, early treatment with MTX is associated with a mean delay in the development of cataract requiring surgery of 3.5 years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17706583", "endSection": "sections.0" }, { "offsetInBeginSection": 1252, "offsetInEndSection": 1316, "text": "MTX seems to be an effective therapy for JIA associated uveitis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15693100", "endSection": "sections.0" } ] }, { "body": "Which are the enzymes involved in the addition of 7-methylguanosine in mRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24200467", "http://www.ncbi.nlm.nih.gov/pubmed/7831320", "http://www.ncbi.nlm.nih.gov/pubmed/24552703", "http://www.ncbi.nlm.nih.gov/pubmed/21170289", "http://www.ncbi.nlm.nih.gov/pubmed/23863084", "http://www.ncbi.nlm.nih.gov/pubmed/729595", "http://www.ncbi.nlm.nih.gov/pubmed/24273643", "http://www.ncbi.nlm.nih.gov/pubmed/6478055", "http://www.ncbi.nlm.nih.gov/pubmed/956186", "http://www.ncbi.nlm.nih.gov/pubmed/11879179", "http://www.ncbi.nlm.nih.gov/pubmed/21118133", "http://www.ncbi.nlm.nih.gov/pubmed/22817748", "http://www.ncbi.nlm.nih.gov/pubmed/2072458", "http://www.ncbi.nlm.nih.gov/pubmed/9707557", "http://www.ncbi.nlm.nih.gov/pubmed/9725672", "http://www.ncbi.nlm.nih.gov/pubmed/1002690", "http://www.ncbi.nlm.nih.gov/pubmed/6649413", "http://www.ncbi.nlm.nih.gov/pubmed/20713356", "http://www.ncbi.nlm.nih.gov/pubmed/22985415", "http://www.ncbi.nlm.nih.gov/pubmed/10662770" ], "ideal_answer": [ "The 7-methylguanosine cap added to the 5\u2032 end of mRNA is essential for efficient gene expression and cell viability. Methylation of the guanosine cap is necessary for the translation of most cellular mRNAs in all eukaryotic organisms in which it has been investigated. In some experimental systems, cap methylation has also been demonstrated to promote transcription, splicing, polyadenylation and nuclear export of mRNA. In the addition of 7-methylguanosine in mRNA involved the RNA polymerase II, RNA guanylyltransferase and RNA guanine-7 methyltransferase enzymes.", "The enzymes involved in the addition of 7-methylguanosine in mRNA are RNA guanylyltransferase and 5'-phosphatase (RNGTT), RNA guanine-7 methyltransferase (RNMT or hMTr1), RNMT-activating mini-protein (RAM), RNA polymerase II, S-adenosylhomocysteine hydrolase (SAHH), and Myc." ], "exact_answer": [ [ "RNA guanylyltransferase and 5'-phosphatase (RNGTT)", "RNA guanylyltransferase and 5'-phosphatase", "RNGTT" ], [ "RNA guanine-7 methyltransferase", "RNA guanine-7 methyltransferase (RNMT or hMTr1)", "RNMT", "hMTr1" ], [ "RNMT-activating mini-protein", "RNMT-activating mini-protein (RAM)", "RAM" ], [ "RNA polymerase II" ], [ "S-adenosylhomocysteine hydrolase", "S-adenosylhomocysteine hydrolase (SAHH)", "SAHH" ], [ "Myc" ] ], "concepts": [ "http://www.uniprot.org/uniprot/MCE1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009452", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008618", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006370", "http://www.biosemantics.org/jochem#4270220", "http://www.uniprot.org/uniprot/RSMG_OENOB", "http://www.uniprot.org/uniprot/MCE1_CAEEL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004484", "http://www.biosemantics.org/jochem#4270249", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.uniprot.org/uniprot/MCE_ASFP4", "http://www.uniprot.org/uniprot/MCE1_DANRE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045762", "http://www.biosemantics.org/jochem#4211619", "http://www.uniprot.org/uniprot/MCE_ASFB7", "http://www.biosemantics.org/jochem#4270250", "http://www.uniprot.org/uniprot/MCE_PBCV1", "http://www.uniprot.org/uniprot/MCE1_HUMAN", "http://www.biosemantics.org/jochem#4269944", "http://www.uniprot.org/uniprot/MCE_ASFK5", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046118", "http://www.uniprot.org/uniprot/MCE_ASFM2", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000340", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004789", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020536", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031533", "http://www.biosemantics.org/jochem#4195237", "http://www.uniprot.org/uniprot/MCE_MIMIV" ], "type": "list", "id": "52f112bb2059c6d71c000002", "snippets": [ { "offsetInBeginSection": 452, "offsetInEndSection": 975, "text": "In mammals, cap synthesis is catalysed by the sequential action of RNGTT (RNA guanylyltransferase and 5'-phosphatase) and RNMT (RNA guanine-7 methyltransferase), enzymes recruited to RNA pol II (polymerase II) during the early stages of transcription. We recently discovered that the mammalian cap methyltransferase is a heterodimer consisting of RNMT and the RNMT-activating subunit RAM (RNMT-activating mini-protein). RAM activates and stabilizes RNMT and thus is critical for cellular cap methylation and cell viability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24200467", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 447, "text": "Synthesis of the methyl cap initiates with the addition of 7-methylguanosine to the initiating nucleotide of RNA pol II (polymerase II) transcripts, which occurs predominantly during transcription and in mammals is catalysed by RNGTT (RNA guanylyltransferase and 5' phosphatase) and RNMT (RNA guanine-7 methyltransferase).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863084", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1006, "text": "The RNMT-activating subunit, RAM (RNMT-activating miniprotein), is also recruited to transcription initiation sites via an interaction with RNMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863084", "endSection": "abstract" }, { "offsetInBeginSection": 786, "offsetInEndSection": 902, "text": "Phosphorylation of the CTD recruits RNGTT and RNMT, the enzymes involved in mRNA capping, to the nascent transcript.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21170289", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 931, "text": "Myc induces methyl cap formation by promoting RNA polymerase II phosphorylation which recruits the capping enzymes to RNA, and by up-regulating the enzyme SAHH (S-adenosylhomocysteine hydrolase), which neutralizes the inhibitory by-product of methylation reactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118133", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 691, "text": "In the present study, we identify the methyltransferase responsible for cap1 formation in human cells, which we call hMTr1 (also known as FTSJD2 and ISG95).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20713356", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 329, "text": "The guanylyltransferase (GTP:mRNA guanylyltransferase, EC 2.7.7.50) reaction responsible for cap formation usually proceeds via a covalent enzyme-GMP intermediate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7831320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "The methylation of the 5' terminal guanosine residue of the cap structure of Semliki Forest virus (SFV) mRNAs has been shown to occur in vitro concomitantly with their synthesis (R. K. Cross and P. J. Gomatos, Virology, 114, 542-554, 1981). The enzyme responsible for this methylation, a guanine-7-methyltransferase, is associated with the SFV replication complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6649413", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 303, "text": "An RNA (guanine-7-)-methyltransferase that specifically methylates the 5'-terminal guanosine residue of RNAs ending in the dinucleoside triphosphate G(5')pppN- has been purified from the cytoplasm of HeLa cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/956186", "endSection": "abstract" } ] }, { "body": "What is HOCOMOCO?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23175603" ], "ideal_answer": [ "HOCOMOCO is a comprehensive collection of human transcription factor binding sites models constructed by integration of binding sequences obtained by both low- and high-throughput methods. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157" ], "type": "summary", "id": "56c8efef5795f9a73e000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "HOCOMOCO: a comprehensive collection of human transcription factor binding sites models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175603", "endSection": "title" }, { "offsetInBeginSection": 569, "offsetInEndSection": 1365, "text": "We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods. To construct position weight matrices to represent these TFBS models, we used ChIPMunk software in four computational modes, including newly developed periodic positional prior mode associated with DNA helix pitch. We selected only one TFBS model per TF, unless there was a clear experimental evidence for two rather distinct TFBS models. We assigned a quality rating to each model. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175603", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 848, "text": "We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175603", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1364, "text": "HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "HOCOMOCO: a comprehensive collection of human transcription factor binding sites models", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175603", "endSection": "title" }, { "offsetInBeginSection": 359, "offsetInEndSection": 1065, "text": "We show that integration of TFBS data from various types of experiments into a single model typically results in the improved model quality probably due to partial correction of source specific technique bias. We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods. To construct position weight matrices to represent these TFBS models, we used ChIPMunk software in four computational modes, including newly developed periodic positional prior mode associated with DNA helix pitch. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175603", "endSection": "abstract" } ] }, { "body": "In which condition was protein S100A7 originally identified?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22189627", "http://www.ncbi.nlm.nih.gov/pubmed/21148126", "http://www.ncbi.nlm.nih.gov/pubmed/21501383", "http://www.ncbi.nlm.nih.gov/pubmed/21551409", "http://www.ncbi.nlm.nih.gov/pubmed/19167844", "http://www.ncbi.nlm.nih.gov/pubmed/20596736" ], "ideal_answer": [ "Psoriasin (S100A7) was originally identified in psoriasis." ], "exact_answer": [ "psoriasis" ], "type": "factoid", "id": "55203ae78e534a4535000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding protein belonging to the multigenic S100 family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22189627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Psoriasin (S100 A7) was discovered two decades ago as a protein abundantly expressed in psoriatic keratinocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501383", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 213, "text": " Psoriasin, originally isolated from psoriasis as an overexpressed molecule of unknown function, has recently been identified as a principal Escherichia coli-killing antimicrobial peptide of healthy skin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21551409", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 650, "text": "Inflammation-prone psoriatic skin constitutively expresses elevated concentrations of S100A7 (psoriasin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21148126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "S100A7 (psoriasin) and S100A15 (koebnerisin) were first identified in inflamed psoriatic skin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20596736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Human psoriasin (S100A7) has originally been described as a member of the family of S100 calcium-binding proteins which is overexpressed in patients suffering from psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19167844", "endSection": "abstract" } ] }, { "body": "Do proton pump inhibitors affect thyroxine absorption?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15073769", "http://www.ncbi.nlm.nih.gov/pubmed/16477543", "http://www.ncbi.nlm.nih.gov/pubmed/22019751", "http://www.ncbi.nlm.nih.gov/pubmed/16918738", "http://www.ncbi.nlm.nih.gov/pubmed/16971728", "http://www.ncbi.nlm.nih.gov/pubmed/18942671", "http://www.ncbi.nlm.nih.gov/pubmed/18996189", "http://www.ncbi.nlm.nih.gov/pubmed/20694403", "http://www.ncbi.nlm.nih.gov/pubmed/7865648", "http://www.ncbi.nlm.nih.gov/pubmed/23565522", "http://www.ncbi.nlm.nih.gov/pubmed/17669709", "http://www.ncbi.nlm.nih.gov/pubmed/9416973", "http://www.ncbi.nlm.nih.gov/pubmed/19942153" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6850734", "o": "Proton Pump Inhibitors" } ], "ideal_answer": [ "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption.\nPatients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017494", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054328" ], "type": "yesno", "id": "513f3ab6bee46bd34c00000f", "snippets": [ { "offsetInBeginSection": 562, "offsetInEndSection": 653, "text": "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20694403", "endSection": "sections.0" }, { "offsetInBeginSection": 313, "offsetInEndSection": 580, "text": "Many commonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19942153", "endSection": "sections.0" }, { "offsetInBeginSection": 1477, "offsetInEndSection": 1582, "text": "Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7865648", "endSection": "sections.0" }, { "offsetInBeginSection": 1744, "offsetInEndSection": 2088, "text": "PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT4 replacement. Patients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17669709", "endSection": "sections.0" } ] }, { "body": "Is PER3 required for CHK2 activation in human cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21070773" ], "ideal_answer": [ "Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells.Per3, a circadian gene, is required for Chk2 activation in human cells.", "Per3, a circadian gene, is required for Chk2 activation in human cells. ", "Per3, a circadian gene, is required for Chk2 activation in human cells.Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,", "Per3 gene, involved in circadian rhythm control, is required for Chk2 activation in human cells." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/CHK2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064447", "http://www.uniprot.org/uniprot/PER3_HUMAN" ], "type": "yesno", "id": "5357b5ecf1005d6b58000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Per3, a circadian gene, is required for Chk2 activation in human cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "title" }, { "offsetInBeginSection": 96, "offsetInEndSection": 233, "text": "Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 376, "text": "Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 508, "text": "Per3 overexpression also led to the inhibition of cell proliferation and apoptotic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 660, "text": "These combined results suggest that Per3 is a checkpoint protein that plays important roles in checkpoint activation, cell proliferation and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 232, "text": "Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 412, "text": "Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage, and this activation depended on ATM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 291, "text": "In addition, Per3 physically interacted with ATM and Chk2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070773", "endSection": "abstract" } ] }, { "body": "What is the typical alteration of the thyroid profile metabolism early after coronary artery bypass graft surgery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6422832", "http://www.ncbi.nlm.nih.gov/pubmed/15843233", "http://www.ncbi.nlm.nih.gov/pubmed/22358266", "http://www.ncbi.nlm.nih.gov/pubmed/12537197", "http://www.ncbi.nlm.nih.gov/pubmed/9010711" ], "ideal_answer": [ "Low T3 Syndrome is the more frequent alteration of thyroid hormone profile early after coronary artery bypass graft surgery." ], "exact_answer": [ "Low T3 syndrome occurs frequently after CABG" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047549", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001026", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013959", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003327", "http://www.disease-ontology.org/api/metadata/DOID:3393" ], "type": "factoid", "id": "532670e7d6d3ac6a34000008", "snippets": [ { "offsetInBeginSection": 988, "offsetInEndSection": 1164, "text": "FT3 concentration dropped significantly (p < 0.0001), reaching its lowest value 12 hours postoperatively. There were no significant differences between CPB and OPCAB patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12537197", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1383, "text": "In on-pump CABG surgery, inflammatory effects encompass activation of total leukocytes, neutrophils and platelets, reduction of serum level of total proteins and albumin and decreased thyroid hormones levels, especially within first postoperative 24 hours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22358266", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1087, "text": "Typical NTIS was observed in all patients, and the FT3 concentration was still reduced by postoperative day 5 (p<0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15843233", "endSection": "abstract" }, { "offsetInBeginSection": 1740, "offsetInEndSection": 1962, "text": "We could demonstrate that CPB induces a low T3 syndrome up to 3 days after surgery. Those patients with low T3 concentrations prior to surgery demonstrate postoperatively a more severe degree of nonthyroidal illness (NTI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9010711", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 872, "text": "It is concluded that the coronary bypass operation evokes a rapid decline in T3, which is not normalized by the TSH induced response of the thyroid gland, while the post-operative period is characterized by a \"low T3 state\". ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6422832", "endSection": "abstract" } ] }, { "body": "Which proteins are involved in actin bundling and filopodia formation and function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17115031", "http://www.ncbi.nlm.nih.gov/pubmed/21283078", "http://www.ncbi.nlm.nih.gov/pubmed/22090504", "http://www.ncbi.nlm.nih.gov/pubmed/14752106", "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "http://www.ncbi.nlm.nih.gov/pubmed/19228738", "http://www.ncbi.nlm.nih.gov/pubmed/20137952", "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "http://www.ncbi.nlm.nih.gov/pubmed/14532112", "http://www.ncbi.nlm.nih.gov/pubmed/16675552", "http://www.ncbi.nlm.nih.gov/pubmed/18835624" ], "ideal_answer": [ "A number of proteins have been found to regulate F-actin bundling and enhance filopodia formation and motility. Among these are Cysteine-rich protein 1 (CRP1), Fascin, Macrophage actin-associated tyrosine phosphorylated protein (MAYP/PSTPIP2), Insulin receptor tyrosine kinase substrate p53 (IRSp53), Missing in metastasis protein (MIM), Eps8, Diaphanous-related formin (dDia2) and Vasodilator-stimulated phosphoprotein (VASP)." ], "exact_answer": [ [ "Cysteine-rich protein 1 (CRP1)" ], [ "Fascin" ], [ "Macrophage actin-associated tyrosine phosphorylated protein (MAYP/PSTPIP2)" ], [ "Insulin receptor tyrosine kinase substrate p53 (IRSp53)" ], [ "Missing in metastasis protein (MIM)" ], [ "Eps8" ], [ "Diaphanous-related formin (dDia2)" ], [ "Vasodilator-stimulated phosphoprotein (VASP)" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011554", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051490", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032432", "http://www.uniprot.org/uniprot/FSCN1_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051764", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051491", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051489", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008840", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046847", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000199", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032233", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032232", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032231", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051017", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070650" ], "type": "list", "id": "5358e067f1005d6b5800000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090504", "endSection": "title" }, { "offsetInBeginSection": 77, "offsetInEndSection": 243, "text": "CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090504", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 362, "text": "Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090504", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 503, "text": "Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090504", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 622, "text": "Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090504", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 655, "text": "F-ascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21283078", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 384, "text": "In this study, we investigated the role of fascin, a cytoskeleton actin-bundling protein involved in the formation of filopodia and cell migration, in prostate cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19228738", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1389, "text": "In cellular models, fascin gene silencing using small interfering RNA in the androgen-independent prostate cancer cell line DU145 decreased cell motility and invasiveness while increasing cell adhesive properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19228738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Fascin is an actin-bundling protein that induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18835624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "endSection": "title" }, { "offsetInBeginSection": 572, "offsetInEndSection": 711, "text": "Overexpression of MAYP decreased CSF-1-induced membrane ruffling and increased filopodia formation, motility and CSF-1-mediated chemotaxis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 935, "text": "The opposite phenotype was observed with reduced expression of MAYP, indicating that MAYP is a negative regulator of CSF-1-induced membrane ruffling and positively regulates formation of filopodia and directional migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1152, "text": "Overexpression of MAYP led to a reduction in total macrophage F-actin content but was associated with increased actin bundling. Consistent with this, purified MAYP bundled F-actin and regulated its turnover in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1228, "text": "In addition, MAYP colocalized with cortical and filopodial F-actin in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1455, "text": "Because filopodia are postulated to increase directional motility by acting as environmental sensors, the MAYP-stimulated increase in directional movement may be at least partly explained by enhancement of filopodia formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15788569", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 369, "text": "We report an unexpected direct association between fascin, an actin-bundling component of filopodia, microspikes and lamellipodial ribs, and protein kinase Calpha (PKCalpha), a regulator of focal adhesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14532112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Fascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20137952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Actin-crosslinking proteins organize actin into highly dynamic and architecturally diverse subcellular scaffolds that orchestrate a variety of mechanical processes, including lamellipodial and filopodial protrusions in motile cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17115031", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 615, "text": "IRSp53, a multi-domain protein that can associate with the Rho-GTPases Rac and Cdc42, participates in these processes mainly through its amino-terminal IMD (IRSp53 and MIM domain). The isolated IMD has actin-bundling activity in vitro and is sufficient to induce filopodia in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17115031", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1087, "text": "Eps8 activates and synergizes with IRSp53 in mediating actin bundling in vitro, enhancing IRSp53-dependent membrane extensions in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17115031", "endSection": "abstract" }, { "offsetInBeginSection": 1238, "offsetInEndSection": 1344, "text": "Consistently, Cdc42-induced filopodia are inhibited following individual removal of either IRSp53 or Eps8.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17115031", "endSection": "abstract" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1562, "text": "Collectively, these results support a model whereby the synergic bundling activity of the IRSp53-Eps8 complex, regulated by Cdc42, contributes to the generation of actin bundles, thus promoting filopodial protrusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17115031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675552", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "Filopodia are highly dynamic finger-like cell protrusions filled with parallel bundles of actin filaments. Previously we have shown that Diaphanous-related formin dDia2 is involved in the formation of filopodia. Another key player for the formation of filopodia across many species is vasodilator-stimulated phosphoprotein (VASP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675552", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 488, "text": "It has been proposed that the essential role of VASP for formation of filopodia is its competition with capping proteins for filament barbed-end interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675552", "endSection": "abstract" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1315, "text": "Only WT DdVASP, but not a mutant lacking the F-actin bundling activity, could rescue the ability of these cells to form WT-like filopodia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675552", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1472, "text": "Our data suggest that DdVASP is complexed with dDia2 in filopodial tips and support formin-mediated filament elongation by bundling nascent actin filaments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675552", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Insulin receptor tyrosine kinase substrate p53 (IRSp53) has been identified as an SH3 domain-containing adaptor that links Rac1 with a Wiskott-Aldrich syndrome family verprolin-homologous protein 2 (WAVE2) to induce lamellipodia or Cdc42 with Mena to induce filopodia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14752106", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 555, "text": "Here, we show that the N-terminal predicted helical stretch of 250 amino acids of IRSp53 is an evolutionarily conserved F-actin bundling domain involved in filopodium formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14752106", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1031, "text": "The IMD alone, derived from either IRSp53 or MIM, induced filopodia in HeLa cells and the formation of tightly packed parallel F-actin bundles in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14752106", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1122, "text": "These results suggest that IRSp53 and MIM belong to a novel actin bundling protein family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14752106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Role of the actin bundling protein fascin in growth cone morphogenesis: localization in filopodia and lamellipodia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "endSection": "title" }, { "offsetInBeginSection": 610, "offsetInEndSection": 699, "text": "Fascin localized to radially oriented actin bundles in lamellipodia (ribs) and filopodia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 873, "text": "Using a fascin antibody and a GFP fascin construct, we found that fascin incorporated into actin bundles from the beginning of growth cone formation at the cut end of axons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1224, "text": "Later, during growth cone morphogenesis when actin ribs shortened, the proximal fascin-free zone of bundles increased, but fascin was retained in the distal, filopodial portion of bundles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1421, "text": "Treatment with tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), which phosphorylates fascin and decreases its affinity for actin, resulted in loss of all actin bundles from growth cones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1618, "text": "Our findings suggest that fascin may be particularly important for the linear structure and dynamics of filopodia and for lamellipodial rib dynamics by regulating filament organization in bundles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169763", "endSection": "abstract" } ] }, { "body": "What does the SAGA complex acronym stands for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25015293", "http://www.ncbi.nlm.nih.gov/pubmed/25441028", "http://www.ncbi.nlm.nih.gov/pubmed/26100014", "http://www.ncbi.nlm.nih.gov/pubmed/24509845", "http://www.ncbi.nlm.nih.gov/pubmed/26528322" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10002967", "o": "C507785" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1700223", "o": "http://linkedlifedata.com/resource/umls/label/A10002967" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10002967", "o": "SAGA complex, S cerevisiae" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1700223", "o": "http://linkedlifedata.com/resource/umls/label/A10002967" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10002967", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0070461", "o": "cellular_component" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0070461", "o": "SAGA family complex" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0070461", "o": "SAGA-type complex" }, { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0000124", "o": "cellular_component" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0000124", "o": "Spt-Ada-Gcn5-acetyltransferase complex" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0000124", "o": "SAGA complex" } ], "ideal_answer": [ "SAGA stands for Spt-Ada-Gcn5-acetyltransferase (SAGA)" ], "exact_answer": [ "Spt-Ada-Gcn5-acetyltransferase" ], "concepts": [ "http://www.uniprot.org/uniprot/SGF29_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000124", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043234", "http://www.uniprot.org/uniprot/SGF73_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036285" ], "type": "factoid", "id": "56b76f496e3f8eaf4c000002", "snippets": [ { "offsetInBeginSection": 146, "offsetInEndSection": 183, "text": "SAGA (Spt-Ada-Gcn5 Acetyltransferase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26528322", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 845, "text": "SAGA (Spt-Ada-Gcn5-acetyltransferase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26100014", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 467, "text": "Spt-Ada-Gcn5-acetyltransferase (SAGA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25015293", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 87, "text": "Spt-Ada-Gcn5-acetyltransferase (SAGA) complex is a transcription coactivator ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24509845", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 105, "text": "the yeast transcriptional coactivator Spt-Ada-Gcn5 acetyltransferase (SAGA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25441028", "endSection": "abstract" } ] }, { "body": "What is the result of the interaction between TSC1 and PLK1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16339216" ], "ideal_answer": [ "Phosphorylated TSC1 (hamartin) interacts with Plk1 independent of TSC2 (tuberin), with all three proteins present in a complex, and negatively regulates the protein levels of Plk1, to control centrosome duplication." ], "concepts": [ "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.uniprot.org/uniprot/PLK1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054730", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596" ], "type": "summary", "id": "5319a7f2b166e2b80600002a", "snippets": [ { "offsetInBeginSection": 663, "offsetInEndSection": 775, "text": "Phosphorylated hamartin interacts with Plk1 independent of tuberin with all three proteins present in a complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339216", "endSection": "abstract" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1146, "text": "Hamartin negatively regulates the protein levels of Plk1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339216", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1293, "text": "Finally, Tsc1(-/-) mouse embryonic fibroblasts (MEFs) have increased number of centrosomes and increased DNA content, compared to Tsc1(+/+) cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339216", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1684, "text": "Both phenotypes are rescued after pre-treatment with the mTOR inhibitor rapamycin. RNAi inhibition of Plk1 in Tsc1(-/-) MEFs failed to rescue the increased centrosome number phenotype. These data reveal a novel subcellular localization for hamartin and a novel interaction partner for the hamartin/tuberin complex and implicate hamartin and mTOR in the regulation of centrosome duplication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339216", "endSection": "abstract" } ] }, { "body": "What are the characteristics of the \"Universal Proteomics Standard 2\" (UPS2)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20823122", "http://www.ncbi.nlm.nih.gov/pubmed/24195105" ], "ideal_answer": [ "The UPS2 proteomic dynamic range standard was introduced by the Association of Biomolecular Resource Facilities Proteomics Standards Research Group in 2006 and it has a dynamic range of 5 orders of magnitude." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012015" ], "type": "summary", "id": "53482bfcaeec6fbd07000010", "snippets": [ { "offsetInBeginSection": 1197, "offsetInEndSection": 1349, "text": "the UPS2 proteomic dynamic range standard introduced by The Association of Biomolecular Resource Facilities Proteomics Standards Research Group in 2006)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20823122", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1109, "text": "Universal Proteomics Standard sample with a dynamic range of 5 orders of magnitude (UPS2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24195105", "endSection": "abstract" } ] }, { "body": "Which polyQ tract protein is linked to Spinocerebellar Ataxia type 2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25027299", "http://www.ncbi.nlm.nih.gov/pubmed/19625506", "http://www.ncbi.nlm.nih.gov/pubmed/24486837", "http://www.ncbi.nlm.nih.gov/pubmed/10973246" ], "ideal_answer": [ "Ataxin-2 is an evolutionarily conserved protein first identified in humans as responsible for spinocerebellar ataxia type 2 (SCA2). The molecular basis of SCA2 is the expansion of a polyglutamine tract in Ataxin-2, encoding a Lsm domain that may bind RNA and a PAM2 motif that enables interaction with the poly (A) binding protein." ], "exact_answer": [ "Ataxin 2" ], "type": "factoid", "id": "56cae60f5795f9a73e00002b", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 343, "text": "Ataxin-2 is an evolutionarily conserved protein first identified in humans as responsible for spinocerebellar ataxia type 2 (SCA2). The molecular basis of SCA2 is the expansion of a polyglutamine tract in Ataxin-2, encoding a Lsm domain that may bind RNA and a PAM2 motif that enables interaction with the poly (A) binding protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25027299", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 722, "text": "In SCA2 brains, we found cytoplasmic, but not nuclear, microaggregates. Mice expressing ataxin-2 with Q58 showed progressive functional deficits accompanied by loss of the Purkinje cell dendritic arbor and finally loss of Purkinje cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10973246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited, neurodegenerative disease caused by an expansion of polyglutamine tracts in the cytosolic protein ataxin-2 (Atx2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625506", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1360, "text": "Our analysis provides valuable information on the evolution and domain structure of Ataxin-2 proteins. Proline-rich motifs that may mediate protein interactions are widespread in Ataxin-2 proteins, but expansion of polyglutamine tracts associated with spinocerebellar ataxia type 2, is present only in primates, as well as some insects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25027299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The expansion of a polyQ repeat within the ataxin-2 protein causes spinocerebellar ataxia type 2 (SCA2). However, neither the precise pathological mechanism nor the physiological functions of ataxin-2 are known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24486837", "endSection": "abstract" } ] }, { "body": "Which are the smallest known subviral pathogens of plants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10494833", "http://www.ncbi.nlm.nih.gov/pubmed/10592219", "http://www.ncbi.nlm.nih.gov/pubmed/15231279", "http://www.ncbi.nlm.nih.gov/pubmed/16519798", "http://www.ncbi.nlm.nih.gov/pubmed/25731957", "http://www.ncbi.nlm.nih.gov/pubmed/25503469", "http://www.ncbi.nlm.nih.gov/pubmed/22345560", "http://www.ncbi.nlm.nih.gov/pubmed/1717335", "http://www.ncbi.nlm.nih.gov/pubmed/16679345", "http://www.ncbi.nlm.nih.gov/pubmed/2672273", "http://www.ncbi.nlm.nih.gov/pubmed/15040183" ], "ideal_answer": [ "Contrary to earlier beliefs, viruses are not the smallest causative agents of infectious diseases. Single-stranded RNAs as small as 246 nucleotides exist in certain higher plants and cause more than a dozen crop diseases. These RNAs have been termed viroids. Viroids are plant subviral pathogens whose genomes are constituted by a single-stranded and covalently closed small RNA molecule that does not encode for any protein.", "Since the discovery of non-coding, small, highly structured, satellite RNAs (satRNAs) and viroids as subviral pathogens of plants , have been of great interest to molecular biologists as possible living fossils of pre-cellular evolution in an RNA world." ], "exact_answer": [ "Viroids" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010944" ], "type": "factoid", "id": "56e0447a51531f7e3300000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Since the discovery of non-coding, small, highly structured, satellite RNAs (satRNAs) and viroids as subviral pathogens of plants , have been of great interest to molecular biologists as possible living fossils of pre-cellular evolution in an RNA world.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731957", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1382, "text": "PFOR2 analysis of the small RNA libraries from grapevine and apple plants led to the discovery of Grapevine latent viroid (GLVd) and Apple hammerhead viroid-like RNA (AHVd-like RNA), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25503469", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1190, "text": "We show that viroids from the two known families are readily identified and their full-length sequences assembled by PFOR from small RNAs sequenced from infected plants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Viroids are plant subviral pathogens whose genomes are constituted by a single-stranded and covalently closed small RNA molecule that does not encode for any protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16679345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Viroids are small, circular, single-stranded RNA molecules that cause several infectious plant diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15231279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Viroids: petite RNA pathogens with distinguished talents.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15231279", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Subviral pathogens of plants: viroids and viroidlike satellite RNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1717335", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Contrary to earlier beliefs, viruses are not the smallest causative agents of infectious diseases. Single-stranded RNAs as small as 246 nucleotides exist in certain higher plants and cause more than a dozen crop diseases. These RNAs have been termed viroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1717335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Subviral pathogens of plants: the viroids", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2672273", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Viroids, satellite RNAs, satellites viruses and the human hepatitis delta virus form the 'brotherhood' of the smallest known infectious RNA agents, known as the subviral RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16519798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Subviral pathogens of plants: the viroids.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2672273", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Viroids, subviral pathogens of plants, are composed of a single-stranded circular RNA of 246-399 nucleotides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10494833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "During 1970 and 1971, I discovered that a devastating disease of potato plants is not caused by a virus, as had been assumed, but by a new type of subviral pathogen, the viroid. Viroids are so small--one fiftieth of the size of the smallest viruses--that many scientists initially doubted their existence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15040183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The database of the smallest known auto-replicable RNA species: viroids and viroid-like RNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10592219", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Viroids, satellite RNAs, satellites viruses and the human hepatitis delta virus form the 'brotherhood' of the smallest known infectious RNA agents, known as the subviral RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16519798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": " Replicating circular RNAs are independent plant pathogens known as viroids, or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs. The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demanding and time-consuming.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25503469", "endSection": "abstract" } ] }, { "body": "What causes Katayama Fever?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24985919", "http://www.ncbi.nlm.nih.gov/pubmed/24916752", "http://www.ncbi.nlm.nih.gov/pubmed/1901428", "http://www.ncbi.nlm.nih.gov/pubmed/19009810", "http://www.ncbi.nlm.nih.gov/pubmed/1411323", "http://www.ncbi.nlm.nih.gov/pubmed/2511623", "http://www.ncbi.nlm.nih.gov/pubmed/15582175", "http://www.ncbi.nlm.nih.gov/pubmed/24469437", "http://www.ncbi.nlm.nih.gov/pubmed/2515622", "http://www.ncbi.nlm.nih.gov/pubmed/16169593", "http://www.ncbi.nlm.nih.gov/pubmed/24176480", "http://www.ncbi.nlm.nih.gov/pubmed/8115806", "http://www.ncbi.nlm.nih.gov/pubmed/22470757", "http://www.ncbi.nlm.nih.gov/pubmed/7676521", "http://www.ncbi.nlm.nih.gov/pubmed/10996126" ], "ideal_answer": [ "Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection." ], "exact_answer": [ "Schistosoma spp" ], "type": "factoid", "id": "56bb621fac7ad10019000009", "snippets": [ { "offsetInBeginSection": 113, "offsetInEndSection": 274, "text": "The laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers is difficult because the number of excreted eggs is often very limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916752", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1272, "text": "Eosinophilia (sometimes exceeding 50%) is often present in patients with acute schistosomiasis (Katayama fever), but may be limited or absent in late fibrotic manifestations of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916752", "endSection": "title" }, { "offsetInBeginSection": 800, "offsetInEndSection": 942, "text": "The specific diagnosis of early schistosomiasis and Katayama fever relies essentially on serologic tests or preferably on PCR (if available). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "BACKGROUND: Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24985919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Schistosomiasis is a helminthic infection that is endemic in tropical and subtropical regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22470757", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 285, "text": "In Africa, it predominantly manifests as urogenital disease, and the main infective agent is Schistosoma hematobium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24469437", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 172, "text": "His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "OBJECTIVES: To investigate the characteristics of imported Katayama fever (acute schistosomiasis) as well as evolution and outcome under treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16169593", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 572, "text": "RESULTS: Twenty-three patients were diagnosed with Katayama fever by Schistosoma egg detection and/or by seroconversion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16169593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "The best therapeutic approach to acute schistosomiasis (Katayama fever) is still unsettled.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2515622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24985919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Acute schistosomiasis, called safari's fever in Africa and Katayama fever in Japan, is an immunoallergic reaction due to transcutaneous penetration of infective cercaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15582175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "[Acute schistosomiasis (Katayama fever)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7676521", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Acute schistosomiasis (Katayama fever): corticosteroid as adjunct therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2511623", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Katayama fever or acute schistosomiasis probably occurs more commonly than is recorded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1901428", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 260, "text": "His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Three distinct syndromes caused by schistosomiasis have been described: cercarial dermatitis or swimmer's itch, acute schistosomiasis or Katayama fever, and chronic schistosomiasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8115806", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 655, "text": "Three well-defined syndromes caused by schistosomiasis mansoni have been described: the stage of invasion, acute schistosomiasis (Katayama fever), and chronic schistosomiasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10996126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Early detection of circulating anodic antigen (CAA) in a case of acute schistosomiasis mansoni with Katayama fever.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1411323", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": " A 35-year-old man presented with fever and severe urticaria after visiting Uganda. His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009810", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 176, "text": "His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009810", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 483, "text": "Three well-defined syndromes caused by schistosomiasis mansoni have been described: the stage of invasion, acute schistosomiasis (Katayama fever), and chronic schistosomiasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10996126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Three distinct syndromes caused by schistosomiasis have been described: cercarial dermatitis or swimmer's itch, acute schistosomiasis or Katayama fever, and chronic schistosomiasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8115806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": " To investigate the characteristics of imported Katayama fever (acute schistosomiasis) as well as evolution and outcome under treatment. Between April 2000 and September 2004, we included prospectively all patients with confirmed diagnosis of Katayama fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16169593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "A 35-year-old man presented with fever and severe urticaria after visiting Uganda. His symptoms were caused by acute invasive schistosomiasis, also known as Katayama fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "To investigate the characteristics of imported Katayama fever (acute schistosomiasis) as well as evolution and outcome under treatment. Between April 2000 and September 2004, we included prospectively all patients with confirmed diagnosis of Katayama fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16169593", "endSection": "abstract" } ] }, { "body": "List clinical trials for prevention of sarcopenia", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21968872", "http://www.ncbi.nlm.nih.gov/pubmed/18615229", "http://www.ncbi.nlm.nih.gov/pubmed/22739566", "http://www.ncbi.nlm.nih.gov/pubmed/23892221", "http://www.ncbi.nlm.nih.gov/pubmed/21159787" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00557388", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_name", "s": "http://data.linkedct.org/resource/condition/11756", "o": "Sarcopenia" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/condition/11756", "o": "Condition #11756 (Sarcopenia)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00557388", "o": "Trial NCT00557388" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00475501", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00475501", "o": "Trial NCT00475501" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00748696", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00748696", "o": "Trial NCT00748696" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00529659", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00529659", "o": "Trial NCT00529659" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00240981", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00240981", "o": "Trial NCT00240981" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00690534", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00690534", "o": "Trial NCT00690534" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00183040", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00183040", "o": "Trial NCT00183040" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00730184", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00730184", "o": "Trial NCT00730184" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00190060", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00190060", "o": "Trial NCT00190060" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00465153", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00465153", "o": "Trial NCT00465153" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00744094", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00744094", "o": "Trial NCT00744094" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00357214", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00357214", "o": "Trial NCT00357214" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00260442", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00260442", "o": "Trial NCT00260442" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00174135", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00174135", "o": "Trial NCT00174135" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00473902", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://data.linkedct.org/resource/linkedct/acronym", "s": "http://data.linkedct.org/resource/trials/NCT00473902", "o": "OTR" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00473902", "o": "Trial NCT00473902" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00725166", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://data.linkedct.org/resource/linkedct/acronym", "s": "http://data.linkedct.org/resource/trials/NCT00725166", "o": "CERA" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00725166", "o": "Trial NCT00725166" } ], "ideal_answer": [ "Several clinical trials with androgen replacement therapy. \nStudy was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis. This trial was registered at clinical trials.gov as NCT00794079" ], "exact_answer": [ [ "androgen replacement trials" ], [ "omega-3 fatty acid supplementation", "NCT00794079" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016032", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055948", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011315" ], "type": "list", "id": "52f893f92059c6d71c00003c", "snippets": [ { "offsetInBeginSection": 154, "offsetInEndSection": 249, "text": "several clinical trials with androgen replacement therapy have failed to show clinical benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23892221", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1220, "text": "Clinical trials are needed to find better interventions for this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22739566", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 935, "text": "emergence of many promising interventions towards this age-related condition (e.g., physical exercise [in particular, resistance training], testosterone, antioxidant supplementations), the need for Phase II trial designs is high. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21968872", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 448, "text": "The objective of this study was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis in older adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159787", "endSection": "abstract" }, { "offsetInBeginSection": 1676, "offsetInEndSection": 1740, "text": "This trial was registered at clinical trials.gov as NCT00794079.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159787", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 689, "text": "The extreme paucity of clinical trials on sarcopenia in literature is mainly due to difficulties in designing studies able to isolate the aging process from its multiple and interconnected consequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18615229", "endSection": "abstract" } ] }, { "body": "Which is the database of molecular recognition features in membrane proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23328413", "http://www.ncbi.nlm.nih.gov/pubmed/23894139", "http://www.ncbi.nlm.nih.gov/pubmed/24093637" ], "ideal_answer": [ "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins.", "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins ", "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins" ], "exact_answer": [ "mpMoRFsDB" ], "type": "factoid", "id": "554140ad182542114d000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "mpMoRFsDB: a database of molecular recognition features in membrane proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894139", "endSection": "title" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1065, "text": "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "mpMoRFsDB: a database of molecular recognition features in membrane proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894139", "endSection": "title" } ] }, { "body": "Which database is available for the identification of chorion proteins in Lepidopteran proteomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23262288" ], "ideal_answer": [ "LepChorionDB" ], "exact_answer": [ "LepChorionDB" ], "type": "factoid", "id": "554148c23f2354b713000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "LepChorionDB, a database of Lepidopteran chorion proteins and a set of tools useful for the identification of chorion proteins in Lepidopteran proteomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "title" }, { "offsetInBeginSection": 365, "offsetInEndSection": 1217, "text": "A database, named LepChorionDB, was constructed by searching 5 different protein databases using class A and B central domain-specific profile Hidden Markov Models (pHMMs), developed in this work. A total of 413 Lepidopteran chorion proteins from 9 moths and 1 butterfly species were retrieved. These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes. LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "LepChorionDB, a database of Lepidopteran chorion proteins and a set of tools useful for the identification of chorion proteins in Lepidopteran proteomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "title" }, { "offsetInBeginSection": 654, "offsetInEndSection": 850, "text": "These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1212, "text": "LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 855, "text": "These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1218, "text": "LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 854, "text": "These data were enriched and organised in order to populate LepChorionDB, the first relational database, available on the web, containing Lepidopteran chorion proteins grouped in A and B classes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1217, "text": "LepChorionDB may provide insights in future functional and evolutionary studies of Lepidopteran chorion proteins and thus, it will be a useful tool for the Lepidopteran scientific community and Lepidopteran genome annotators, since it also provides access to the two pHMMs developed in this work, which may be used to discriminate A and B class chorion proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262288", "endSection": "abstract" } ] }, { "body": "Are there any clinical trials of the effect of evening primrose oil on postmenopausal symptoms ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17593379", "http://www.ncbi.nlm.nih.gov/pubmed/12435217", "http://www.ncbi.nlm.nih.gov/pubmed/8136666", "http://www.ncbi.nlm.nih.gov/pubmed/14716179", "http://www.ncbi.nlm.nih.gov/pubmed/23625331", 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(IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16753687", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 937, "text": "Emphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15292498", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1490, "text": "Nonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15292498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625331", "endSection": "title" }, { "offsetInBeginSection": 180, "offsetInEndSection": 305, "text": "The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625331", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1582, "text": " The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625331", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 977, "text": "Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17593379", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1042, "text": "Single clinical trials have found no benefit for dong quai, evening primrose oil,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14716179", "endSection": "abstract" }, { "offsetInBeginSection": 1810, "offsetInEndSection": 1881, "text": "Single clinical trials have found that dong quai, evening primrose oil,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12435217", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 214, "text": "To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN: Randomised, double blind, placebo controlled study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8136666", "endSection": "abstract" } ] }, { "body": "Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11906", "http://www.ncbi.nlm.nih.gov/pubmed/25256446", "http://www.ncbi.nlm.nih.gov/pubmed/26029718", "http://www.ncbi.nlm.nih.gov/pubmed/14643388", "http://www.ncbi.nlm.nih.gov/pubmed/17805474", "http://www.ncbi.nlm.nih.gov/pubmed/16702882", "http://www.ncbi.nlm.nih.gov/pubmed/8935410", "http://www.ncbi.nlm.nih.gov/pubmed/19343043", "http://www.ncbi.nlm.nih.gov/pubmed/6442343", "http://www.ncbi.nlm.nih.gov/pubmed/20206419", "http://www.ncbi.nlm.nih.gov/pubmed/15639117", "http://www.ncbi.nlm.nih.gov/pubmed/25217571", "http://www.ncbi.nlm.nih.gov/pubmed/8552676", "http://www.ncbi.nlm.nih.gov/pubmed/19862843", "http://www.ncbi.nlm.nih.gov/pubmed/19371716", 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"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid \u03b1-glucosidase (GAA))", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25217571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Pompe disease is an autosomal recessive myopathic disorder caused by the deficiency of lysosomal acid \u03b1-glucosidase (GAA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25256446", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 142, "text": "Acid \u03b1-glucosidase deficiency, that is, Pompe disease, is a glycogenosis for which enzyme replacement therapy (ERT) is available", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25786784", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 841, "text": "The analysis revealed that the amino acid substitutions causing a processing or transport defect responsible for Pompe disease were widely spread over all of the five domains comprising the acid alpha-glucosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19343043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20206419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Glycogen storage disease type II (GSDII; Pompe disease or acid maltase deficiency) is an autosomal recessive disorder caused by lysosomal acid alpha-glucosidase (AalphaGlu) deficiency and manifests predominantly as skeletal muscle weakness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17095274", "endSection": "abstract" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1742, "text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17805474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14643388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19862843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9505277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19775921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702882", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11468225", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25036864", "endSection": "title" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1577, "text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17805474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12409258", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12409258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 457, "text": "As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9668092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8935410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14643388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12409258", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19343043", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15585405", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25036864", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15639117", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1578, "text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17805474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9505277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": " Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase. Trials with recombinant human acid alpha-glucosidase enzyme replacement therapy (ERT) show a decrease in left ventricular mass and improved function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": " Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15639117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Pompe disease is caused by the congenital deficiency of the lysosomal enzyme acid alpha-glucosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9883081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6442343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": " Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19862843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9505277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8935410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19343043", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19862843", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1579, "text": "Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17805474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702882", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Mutations in alpha-glucosidase cause accumulation of glycogen in lysosomes, resulting in Pompe disease, a lysosomal storage disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19371716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15639117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8552676", "endSection": "abstract" } ] }, { "body": "Which kinase is inhibited by Tripolin A?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23516487" ], "ideal_answer": [ "Tripolin A reduced the localization of pAurora A on spindle microtubules (MTs), affected centrosome integrity, spindle formation and length, as well as MT dynamics in interphase, consistent with Aurora A inhibition by RNAi or other specific inhibitors, such as MLN8054 or MLN8237. Interestingly, Tripolin A affected the gradient distribution towards the chromosomes, but not the MT binding of HURP (Hepatoma Up-Regulated Protein), a MT-associated protein (MAP) and substrate of the Aurora A kinase. Therefore Tripolin A reveals a new way of regulating mitotic MT stabilizers through Aurora A phosphorylation. Mitotic regulators exhibiting gain of function in tumor cells are considered useful cancer therapeutic targets for the development of small-molecule inhibitors.", "Tripolin A inhibits Aurora A kinase activity both in vitro and in human cells." ], "exact_answer": [ "Aurora A" ], "type": "factoid", "id": "56cb9b065795f9a73e000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP's distribution on microtubules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516487", "endSection": "title" }, { "offsetInBeginSection": 161, "offsetInEndSection": 446, "text": "The human Aurora kinases are a family of such targets. In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro. In human cells however, only Tripolin A acted as an Aurora A inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516487", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 372, "text": "In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP's distribution on microtubules", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516487", "endSection": "title" }, { "offsetInBeginSection": 217, "offsetInEndSection": 446, "text": "In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro. In human cells however, only Tripolin A acted as an Aurora A inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516487", "endSection": "abstract" } ] }, { "body": "Is the optogenetics tool ChR2 light-sensitive?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23380919", "http://www.ncbi.nlm.nih.gov/pubmed/25571406", "http://www.ncbi.nlm.nih.gov/pubmed/23002710", "http://www.ncbi.nlm.nih.gov/pubmed/24068903", "http://www.ncbi.nlm.nih.gov/pubmed/24518144", "http://www.ncbi.nlm.nih.gov/pubmed/24509078", "http://www.ncbi.nlm.nih.gov/pubmed/23366158", "http://www.ncbi.nlm.nih.gov/pubmed/25518365", "http://www.ncbi.nlm.nih.gov/pubmed/24026336", "http://www.ncbi.nlm.nih.gov/pubmed/25796616", "http://www.ncbi.nlm.nih.gov/pubmed/23056472", "http://www.ncbi.nlm.nih.gov/pubmed/23664865", "http://www.ncbi.nlm.nih.gov/pubmed/25483880", "http://www.ncbi.nlm.nih.gov/pubmed/25060859", "http://www.ncbi.nlm.nih.gov/pubmed/25303540", "http://www.ncbi.nlm.nih.gov/pubmed/24555016", "http://www.ncbi.nlm.nih.gov/pubmed/24022017" ], "ideal_answer": [ "Channelrhodospin-2 (ChR2) is a light-sensitive ion channel that has emerged as new optogenetics tool." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062308" ], "type": "yesno", "id": "56e073ad51531f7e3300000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068903", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 993, "text": "Light-sensitive genes chiefly including the genetically targeted light-gated channels channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) cause intracellular ion flow during optical illumination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23002710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Computational optogenetics: empirically-derived voltage- and light-sensitive channelrhodopsin-2 model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068903", "endSection": "title" }, { "offsetInBeginSection": 561, "offsetInEndSection": 979, "text": "The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Channelrhodopsins-2 (ChR2) are a class of light sensitive proteins that offer the ability to use light stimulation to regulate neural activity with millisecond precision.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24026336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The most widely used optogenetic tool, Channelrhodopsin2 (ChR2), is both light- and voltage-sensitive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25060859", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 432, "text": "Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell types over behaviorally-relevant timescales. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24022017", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1334, "text": "Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24509078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Channelrhodopsin-2 (ChR2) from the green alga Chlamydomonas reinhardtii functions as a light-gated cation channel that has been developed as an optogenetic tool to stimulate specific nerve cells in animals and control their behavior by illumination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25796616", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 562, "text": "Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24509078", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 563, "text": "The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "The most widely used optogenetic tool, Channelrhodopsin2 (ChR2), is both light- and voltage-sensitive. A light-triggered action potential or light-driven perturbations of ongoing electrical activity provide instant voltage feedback, shaping ChR2 current.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25060859", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 432, "text": " Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell types over behaviorally-relevant timescales.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24022017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068903", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 994, "text": "It allows neurons to express light-sensitive genes that enable the identification, dissection, and manipulation of specific neural populations and their connections in the tissues and organs of awake animals with unprecedented spatial and temporal precision. Light-sensitive genes chiefly including the genetically targeted light-gated channels channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) cause intracellular ion flow during optical illumination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23002710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 512, "text": "Channelrhodopsin-2 (ChR2) from the green alga Chlamydomonas reinhardtii functions as a light-gated cation channel that has been developed as an optogenetic tool to stimulate specific nerve cells in animals and control their behavior by illumination. The molecular mechanism of ChR2 has been extensively studied by a variety of spectroscopic methods, including light-induced difference Fourier transform infrared (FTIR) spectroscopy, which is sensitive to structural changes in the protein upon light activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25796616", "endSection": "abstract" } ] }, { "body": "Is the Prostate- Specific Antigen (PSA) test relevant only for prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12088291", "http://www.ncbi.nlm.nih.gov/pubmed/9494603", "http://www.ncbi.nlm.nih.gov/pubmed/7544735", "http://www.ncbi.nlm.nih.gov/pubmed/24223021", "http://www.ncbi.nlm.nih.gov/pubmed/18808732", "http://www.ncbi.nlm.nih.gov/pubmed/9494604", "http://www.ncbi.nlm.nih.gov/pubmed/20065953", "http://www.ncbi.nlm.nih.gov/pubmed/15530599", "http://www.ncbi.nlm.nih.gov/pubmed/9329582", "http://www.ncbi.nlm.nih.gov/pubmed/19579539", "http://www.ncbi.nlm.nih.gov/pubmed/15925651", "http://www.ncbi.nlm.nih.gov/pubmed/11583357", "http://www.ncbi.nlm.nih.gov/pubmed/17559560", "http://www.ncbi.nlm.nih.gov/pubmed/23588999", "http://www.ncbi.nlm.nih.gov/pubmed/17489318", "http://www.ncbi.nlm.nih.gov/pubmed/23400279", "http://www.ncbi.nlm.nih.gov/pubmed/18355899", "http://www.ncbi.nlm.nih.gov/pubmed/18569246", "http://www.ncbi.nlm.nih.gov/pubmed/17233806", "http://www.ncbi.nlm.nih.gov/pubmed/7687205", "http://www.ncbi.nlm.nih.gov/pubmed/10697616" ], "ideal_answer": [ "No, although the PSA test can detect high levels of PSA that may indicate the presence of prostate cancer, many other conditions, such as an enlarged or inflamed prostate, can also increase PSA levels." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011471", "http://www.uniprot.org/uniprot/KLK3_MACFA", "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.disease-ontology.org/api/metadata/DOID:10286", "http://www.uniprot.org/uniprot/KLK3_MACMU", "http://www.uniprot.org/uniprot/KLK3_HUMAN" ], "type": "yesno", "id": "5327139ad6d3ac6a3400000d", "snippets": [ { "offsetInBeginSection": 13, "offsetInEndSection": 129, "text": "rostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer death in men", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24223021", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 436, "text": "PSA is known to be prostate specific, but not PCa specific", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24223021", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 96, "text": "deficiencies of serum PSA as a prostate-cancer-specific diagnostic test are well recognized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20065953", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 206, "text": "medical debate surrounding the use of the prostate-specific antigen (PSA) test for prostate cancer screening", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19579539", "endSection": "abstract" }, { "offsetInBeginSection": 2712, "offsetInEndSection": 2834, "text": "The clinical relevance of this surprisingly high rate of prostate cancer in men with a normal PSA is yet to be determined ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15925651", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 159, "text": "Rapid uptake of prostate-specific antigen (PSA) testing has occurred in the United States despite inconclusive evidence regarding mortality benefit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15530599", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 173, "text": "Routine cancer screening with prostate-specific antigen (PSA) is controversial, and practice guidelines recommend that men be counseled about its risks and benefits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12088291", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1135, "text": "Prostate carcinoma was histologically confirmed in 14 (0.66%) of the men, nine times in the early stage (T2) and five times in the clinical stage (T3), corresponding to an incidence of circa 650 cases per 100,000 men in the target age group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11583357", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1278, "text": "This newly developed PSA test system can enhance the acceptance rate and effectiveness of medical check-ups for prostate cancer,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11583357", "endSection": "abstract" }, { "offsetInBeginSection": 1484, "offsetInEndSection": 1601, "text": "PSA can be used reliably as a unique tool in the follow-up of patients for the early detection of progressive disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7544735", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 831, "text": "PSA showed negative predictive values of 82 and 77%, respectively, using 4 and 10 ng/ml as cutoff points", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7544735", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 200, "text": "have assessed the feasibility of using fixed-limit criteria based on medical relevance and biological variation for evaluating the analytical performance of the prostate-specific antigen (PSA) test", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7687205", "endSection": "abstract" } ] }, { "body": "List symptoms of Hakim Triad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19823916", "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "http://www.ncbi.nlm.nih.gov/pubmed/21194654", "http://www.ncbi.nlm.nih.gov/pubmed/20568668" ], "ideal_answer": [ "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence." ], "exact_answer": [ [ "dementia" ], [ "gait disturbances" ], [ "urinary incontinence" ] ], "type": "list", "id": "56bdfa73ef6e394741000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "Normal pressure hydrocephalus (NPH) is a clinical triad of gait disturbance, dementia, and urinary incontinence combined with radiographic findings of ventriculomegaly and laboratory findings of normal cerebrospinal fluid pressures. Although it was first described by Hakim and Adams in 1965, there is no formal definition of NPH, causing discrepancy in its incidence in various studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21194654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "INTRODUCTION: Normal-pressure hydrocephalus (NPH) is a chronic neurological disorder characterized by enlarged ventricles and a triad of clinical symptoms affecting gait, cognition, and urinary continence. Salom\u00f3n Hakim first identified the syndrome in 1957 at the Hospital San Juan de Dios in Bogot\u00e1, Colombia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20568668", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 668, "text": "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 1006, "text": "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Chronic (normotensive or low pressure) hydrocephalus is characterized clinically by gait disturbance, cognitive and urinary impairment, known as Hakim's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19823916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 677, "text": "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "BACKGROUND: Chronic (normotensive or low pressure) hydrocephalus is characterized clinically by gait disturbance, cognitive and urinary impairment, known as Hakim's triad. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19823916", "endSection": "abstract" } ] }, { "body": "Which is the cellular target of gefitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19276163", "http://www.ncbi.nlm.nih.gov/pubmed/18089711", "http://www.ncbi.nlm.nih.gov/pubmed/23255952" ], "ideal_answer": [ "The specific cellular target of Gefitinib (Iressa) is the epidermal growth factor receptor (EGFR)." ], "exact_answer": [ "Epidermal growth factor receptor (EGFR)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058990", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016503", "http://www.biosemantics.org/jochem#4274201", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011958", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005006", "http://www.uniprot.org/uniprot/EGFR_CHICK" ], "type": "factoid", "id": "53188480b166e2b806000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Gefitinib, the specific inhibitor of the epidermal growth factor receptor (EGFR), may cause growth delay in cancer cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23255952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Gefitinib (Iressa) is a specific and effective epidermal growth factor receptor inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) that causes growth delay in cancer cell lines and human tumor xenografts expressing high levels of EGFR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18089711", "endSection": "abstract" } ] }, { "body": "What kind of bonds are connecting keratin molecules?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24276370", "http://www.ncbi.nlm.nih.gov/pubmed/19925868", "http://www.ncbi.nlm.nih.gov/pubmed/24971553", "http://www.ncbi.nlm.nih.gov/pubmed/24367993", "http://www.ncbi.nlm.nih.gov/pubmed/23466495", "http://www.ncbi.nlm.nih.gov/pubmed/25947341", "http://www.ncbi.nlm.nih.gov/pubmed/22705788", "http://www.ncbi.nlm.nih.gov/pubmed/19412554", "http://www.ncbi.nlm.nih.gov/pubmed/22683767" ], "ideal_answer": [ "cystine disulfide bonds\namide bonds\nhydrogen bonds" ], "exact_answer": [ [ "cystine disulfide bonds" ], [ "amide bonds" ], [ "hydrogen bonds" ] ], "type": "list", "id": "56f96333cf1c325851000004", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 213, "text": " Feathers and hair consist of cornified epidermal keratinocytes in which proteins are crosslinked via disulfide bonds between cysteine residues of structural proteins to establish mechanical resilience.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25947341", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 237, "text": " The method involves the generation of thiols by controlled reduction of cystine disulfide bonds in keratin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24367993", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1313, "text": "ossible chemical bonds formed between alpha-keratins and KAbetaPs may derive from electrostatic interactions in addition to cross-linking through disulphide bonds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276370", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 254, "text": "The method involves the generation of thiols by controlled reduction of cystine disulfide bonds in the keratin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971553", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 889, "text": "e solubility test in the dithiothreitol/urea extraction buffer, the amino acid composition analysis and studies on keratin secondary structures suggest that the improved stability in water of thermally treated mats can be ascribed to the formation of amide bonds between acid and basic groups of some amino acid side chains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466495", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1045, "text": "s the energy involved in the formation of disulfide bonds is much greater than that of hydrogen bonds or van der Waals interactions the structural transition is likely to be dominated by the requirement that the bonded cysteine residues occur at closely equivalent axial positions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683767", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 764, "text": "The interface of the K5-K14 coiled-coil heterodimer has asymmetric salt bridges, hydrogen bonds and hydrophobic contacts, and its surface exhibits a notable charge polarization. A trans-dimer homotypic disulfide bond involving Cys367 in K14's stutter region occurs in the crystal and in skin keratinocytes, where it is concentrated in a keratin filament cage enveloping the nucleus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22705788", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1753, "text": " the alpha helices which are stabilized by hydrogen bonds and the alpha-helical coiled coils which are stabilized by hydrophobic interactions, is more sensitive to radiation than the supramolecular architecture of the keratin filament and the filament packing within the keratin associated proteins matrix, which is stabilized by disulphide bonds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19925868", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 768, "text": ". A good solvent attacks the disulfide bonds between cystine molecules and hydrates the hair shaft.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412554", "endSection": "abstract" } ] }, { "body": "Is autism one of the characteristics of Moebius syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15736079", "http://www.ncbi.nlm.nih.gov/pubmed/22832772", "http://www.ncbi.nlm.nih.gov/pubmed/20621443", "http://www.ncbi.nlm.nih.gov/pubmed/19255803", "http://www.ncbi.nlm.nih.gov/pubmed/1623312", "http://www.ncbi.nlm.nih.gov/pubmed/2929356" ], "ideal_answer": [ "Moebius syndrome is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius syndrome with autism spectrum disorders (ASDs) has been suggested in early studies with heterogenous age groups." ], "exact_answer": "yes", "type": "yesno", "id": "5727b6410fd6f91b6800001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "The diagnosis of Moebius syndrome, a rare congenital disorder, is primarily based on congenital facial and abducent nerve palsy. Involvement of other cranial nerves is also common. Occasionally the V, X, XI, and XII cranial nerves are involved, resulting in a difficulty to chew, swallow, and cough, which often leads to respiratory complications. Mental retardation and autism have been reported in some cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22832772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19255803", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 1069, "text": "Certain genetic syndromes are providing us with extremely valuable information about the role played by genetics in autism. This is the case of the following syndromes: Angelman syndrome, Prader-Willi syndrome, 15q11-q13 duplication, fragile X syndrome, fragile X premutation, deletion of chromosome 2q, XYY syndrome, Smith-Lemli-Opitz syndrome, Apert syndrome, mutations in the ARX gene, De Lange syndrome, Smith-Magenis syndrome, Williams syndrome, Rett syndrome, Noonan syndrome, Down syndrome, velo-cardio-facial syndrome, myotonic dystrophy, Steinert disease, tuberous sclerosis, Duchenne's disease, Timothy syndrome, 10p terminal deletion, Cowden syndrome, 45,X/46,XY mosaicism, Myhre syndrome, Sotos syndrome, Cohen syndrome, Goldenhar syndrome, Joubert syndrome, Lujan-Fryns syndrome, Moebius syndrome, hypomelanosis of Ito, neurofibromatosis type 1, CHARGE syndrome and HEADD syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15736079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Seventeen children and young adults with Moebius syndrome were examined with a view to finding symptoms of autism. Some 40% of the group showed all or many of the symptoms typical of autistic disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2929356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Fifty-nine cases with infantile autism/autistic disorder were subclassified according to associated medical condition (fragile-X, tuberous sclerosis, neurofibromatosis, hypo-melanosis of Ito, Moebius syndrome, Rett syndrome, and a 'new' syndrome associated with a marker chromosome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1623312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Autism spectrum disorders in children and adolescents with Moebius sequence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19255803", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20621443", "endSection": "title" }, { "offsetInBeginSection": 281, "offsetInEndSection": 427, "text": "A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19255803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Autistic behaviour in Moebius syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2929356", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 393, "text": "The high frequency of autistic symptoms in Moebius syndrome might be a marked overrepresentation and could be suggestive of a common underlying neurobiological deficit at the brainstem level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2929356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Autism spectrum disorders in children and adolescents with Moebius sequence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19255803", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20621443", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Autistic behaviour in Moebius syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2929356", "endSection": "title" } ] }, { "body": "Is Sarcolipin a regulatory/inhibitory protein of the Calcium ATPase SERCA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16519897", "http://www.ncbi.nlm.nih.gov/pubmed/17515962", "http://www.ncbi.nlm.nih.gov/pubmed/18081313", "http://www.ncbi.nlm.nih.gov/pubmed/12237298", "http://www.ncbi.nlm.nih.gov/pubmed/20833651", "http://www.ncbi.nlm.nih.gov/pubmed/12032137", "http://www.ncbi.nlm.nih.gov/pubmed/22561503", "http://www.ncbi.nlm.nih.gov/pubmed/22496245", "http://www.ncbi.nlm.nih.gov/pubmed/16036219", "http://www.ncbi.nlm.nih.gov/pubmed/16365042", "http://www.ncbi.nlm.nih.gov/pubmed/17971438", "http://www.ncbi.nlm.nih.gov/pubmed/23362265", "http://www.ncbi.nlm.nih.gov/pubmed/19631655", "http://www.ncbi.nlm.nih.gov/pubmed/15556994", "http://www.ncbi.nlm.nih.gov/pubmed/22961106", "http://www.ncbi.nlm.nih.gov/pubmed/23455424", "http://www.ncbi.nlm.nih.gov/pubmed/21697544", "http://www.ncbi.nlm.nih.gov/pubmed/23341466" ], "ideal_answer": [ "Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR) and it is a newly identified regulator of the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure. Sarcolipin is a key regulator of SERCA2a in atria.", "Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport.Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4264789", "http://www.uniprot.org/uniprot/SARCO_MOUSE", "http://www.uniprot.org/uniprot/SARCO_HUMAN", "http://www.uniprot.org/uniprot/SARCO_RAT", "http://www.uniprot.org/uniprot/SARCO_RABIT", "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053498" ], "type": "yesno", "id": "55016397e9bde69634000006", "snippets": [ { "offsetInBeginSection": 509, "offsetInEndSection": 896, "text": "The activity of SERCA is regulated by two small, homologous membrane proteins called phospholamban (PLB, also known as PLN) and sarcolipin (SLN). Detailed structural information explaining this regulatory mechanism has been lacking, and the structural features defining the pathway through which cytoplasmic Ca(2+) enters the intramembranous binding sites of SERCA have remained unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23455424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Sarco(endo)plasmic reticulum Ca(2+)ATPase (SERCA) pump activity is modulated by phospholamban (PLB) and sarcolipin (SLN) in cardiac and skeletal muscle. Recent data suggest that SLN could play a role in muscle thermogenesis by promoting uncoupling of the SERCA pump", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23341466", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 260, "text": "Here we show that sarcolipin (Sln), a newly identified regulator of the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump, is necessary for muscle-based thermogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22961106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Sarcolipin (SLN) is a key regulator of sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and its expression is altered in diseased atrial myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496245", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1433, "text": "Together, these findings indicate that ablation of SLN results in increased SERCA activity and SR Ca(2+) load, which, in turn, could cause abnormal intracellular Ca(2+) handling and atrial remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Sarcolipin (SLN) inhibits sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pumps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697544", "endSection": "abstract" }, { "offsetInBeginSection": 1552, "offsetInEndSection": 1909, "text": "These results show that 1) SLN regulates Ca(2+)-ATPase activity thereby regulating contractile kinetics in at least some skeletal muscles, 2) the functional significance of SLN is graded to the endogenous SLN expression level, and 3) SLN inhibitory effects on SERCA function are relieved in response to repeated contractions thus enhancing relaxation rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697544", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 684, "text": "The SERCA pump was constitutively activated in both atrial and ventricular chambers of the mouse heart by ablating its key regulators, phospholamban (PLN) and sarcolipin (SLN). The double-knockout (dKO) mice for PLN and SLN showed increased SERCA pump activity, Ca(2+) transients and SR Ca(2+) load, and developed cardiac hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20833651", "endSection": "abstract" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1194, "text": "Our findings also emphasize the need for dynamic regulation of the SERCA pump by PLN and/or SLN to maintain cardiac contractility in normal conditions and during pathophysiological states.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20833651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19631655", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 281, "text": "The inhibitory effect of SLN on cardiac SR Ca2+ ATPase (SERCA) pump can be relieved by beta-adrenergic stimulation, which indicates that SLN is a reversible inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19631655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and is expressed abundantly in atria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17971438", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1249, "text": "Our study documented that sarcolipin is a key regulator of SERCA2a in atria. Importantly, our data demonstrate the existence of distinct modulators for the SERCA pump in the atria and ventricles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17971438", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 494, "text": "Sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) is a membrane protein that catalyzes the ATP-dependent transport of Ca(2+) from the cytosol to the SR. The activity of SERCA is inhibited by phospholamban (PLN) and sarcolipin (SLN), and all these proteins participate in maintaining the normal intracellular calcium handling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17515962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Sarcolipin (SLN) is an integral membrane protein that is expressed in both skeletal and cardiac muscle, where it inhibits SERCA (calcium ATPase) by lowering its apparent Ca2+ affinity in a manner similar to that of its homologue phospholamban (PLN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16519897", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1271, "text": "Remarkably, each domain of SLN behaves in a manner similar to that of the corresponding domains in PLN, supporting the hypothesis that both SLN and PLN bind SERCA in the same groove and with similar mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16519897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 516, "text": "The role of sarcolipin (SLN) in cardiac physiology was critically evaluated by generating a transgenic (TG) mouse model in which the SLN to sarco(endoplasmic)reticulum (SR) Ca(2+) ATPase (SERCA) ratio was increased in the ventricle. Overexpression of SLN decreases SR calcium transport function and results in decreased calcium transient amplitude and rate of relaxation. SLN TG hearts exhibit a significant decrease in rates of contraction and relaxation when assessed by ex vivo work-performing heart preparations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365042", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1296, "text": "We conclude that SLN is a novel regulator of SERCA pump activity, and its inhibitory effect can be reversed by beta-adrenergic agonists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Sarcolipin, a homologue of phospholamban, regulates Ca2+ uptake through the interaction with sarcoplasmic reticulum Ca2+ ATPase (SERCA) and is predominantly expressed in the atrial muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16036219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Sarcolipin (SLN) and phospholamban (PLN) are effective inhibitors of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15556994", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1450, "text": "These results show that NF-SLN expression impairs muscle contractile function by inhibiting SERCA function and diminishing sarcoplasmic reticulum Ca(2+) stores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12237298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Sarcolipin (SLN) is an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs) in vitro, but its function in vivo has not been defined. NF-SLN cDNA (SLN tagged N-terminally with a FLAG epitope) was introduced into rat soleus muscle in one hindlimb by plasmid injection and electrotransfer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12237298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Sarcolipin (SLN), a regulator of the sarco(endo)plasmic reticulum Ca(2+)-ATPase of fast-twitch skeletal muscle (SERCA1a), is also expressed in cardiac and slow-twitch skeletal muscles where phospholamban (PLN) and SERCA2a are expressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12032137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Sarco(endo)plasmic reticulum calcium ATPase (SERCA) inhibition by sarcolipin is encoded in its luminal tail.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23362265", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is regulated in a tissue-dependent manner via interaction with the short integral membrane proteins phospholamban (PLN) and sarcolipin (SLN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23362265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Phospholamban (PLN) and sarcolipin (SLN) are two single-pass membrane proteins that regulate Ca2+-ATPase (SERCA), an ATP-driven pump that translocates calcium ions into the lumen of the sarcoplasmic reticulum, initiating muscle relaxation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18081313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is regulated in a tissue-dependent manner via interaction with the short integral membrane proteins phospholamban (PLN) and sarcolipin (SLN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23362265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "[Research progress of sarcolipin-a new regulatory protein of sarcoplasmic reticulum Ca2+ ATPase].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561503", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Phospholamban (PLN) and sarcolipin (SLN) are two single-pass membrane proteins that regulate Ca2+-ATPase (SERCA), an ATP-driven pump that translocates calcium ions into the lumen of the sarcoplasmic reticulum, initiating muscle relaxation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18081313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Sarcolipin (SLN) is an integral membrane protein that is expressed in both skeletal and cardiac muscle, where it inhibits SERCA (calcium ATPase) by lowering its apparent Ca2+ affinity in a manner similar to that of its homologue phospholamban (PLN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16519897", "endSection": "abstract" } ] }, { "body": "What is the risk of developing acute myelogenous leukemia in Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8068955", "http://www.ncbi.nlm.nih.gov/pubmed/9207444", "http://www.ncbi.nlm.nih.gov/pubmed/1548931" ], "ideal_answer": [ "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia.", "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia " ], "exact_answer": [ "At least 15%, based on the International Fanconi Anemia Registry (IFAR)" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13636", "http://www.disease-ontology.org/api/metadata/DOID:8692", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015470", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007951" ], "type": "factoid", "id": "54ede76294afd61504000008", "snippets": [ { "offsetInBeginSection": 1440, "offsetInEndSection": 1519, "text": "Sixteen of the 59 FA-C patients (27%) have developed acute myelogenous leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9207444", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 895, "text": "Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8068955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1548931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1548931", "endSection": "abstract" } ] }, { "body": "How many different mutations have been associated with Muenke syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15241680", "http://www.ncbi.nlm.nih.gov/pubmed/22038757", "http://www.ncbi.nlm.nih.gov/pubmed/19215249", "http://www.ncbi.nlm.nih.gov/pubmed/19755431", "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "http://www.ncbi.nlm.nih.gov/pubmed/23378035" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18449528", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A11927462" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A17680562" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11927462", "o": "MUENKE SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": 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Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "NCI: A rare autosomal dominant inherited disorder caused by mutations in the FGFR3 gene. It is characterized by premature fusion of cranial bones, resulting in head shape abnormalities, flattened cheekbones, and wide-set eyes." }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/id/C0010278" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11993001", "o": "CRS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18466196", "o": "Craniostenoses" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12007160", "o": "CRANIOSYNOSTOSIS, TYPE 1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17867080", "o": "Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18447707", "o": "Craniosynostosis Plagiocephalies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0476812", "o": "craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469337", "o": "Synostotic Plagiocephaly" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8356736", "o": "Premature closure of cranial sutures" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11935450", "o": "CRS1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18457001", "o": "Craniostenosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18447706", "o": "Plagiocephaly, 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"http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11978039", "o": "MUENKE SYNDROME, PRO250ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11978039" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11992529", "o": "FGFR3, PRO250ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11992529" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/relation/R60667887" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/relation/R60508185" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/omim", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "http://bio2rdf.org/omim:134934" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "Muenke syndrome, 602849" } ], "ideal_answer": [ "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3)." ], "exact_answer": [ "One" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "factoid", "id": "52c7311903868f1b0600001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 483, "text": "The associated of FGFR3 mutations with craniosynostosis has been restricted to three mutations, the common p.Pro250Arg in Muenke syndrome, p.Ala391Glu in Crouzon syndrome with acanthosis nigricans, and p.Pro250Leu identified in a family with isolated craniosynostosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038757", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 437, "text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 808, "text": " Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19755431", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 542, "text": "The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19215249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15241680", "endSection": "abstract" } ] }, { "body": "How can the fetal Rhesus be determined with non-invasive testing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24778561", "http://www.ncbi.nlm.nih.gov/pubmed/25380024", "http://www.ncbi.nlm.nih.gov/pubmed/21244652", "http://www.ncbi.nlm.nih.gov/pubmed/23024794", "http://www.ncbi.nlm.nih.gov/pubmed/10985940", "http://www.ncbi.nlm.nih.gov/pubmed/24204719", "http://www.ncbi.nlm.nih.gov/pubmed/22386678", "http://www.ncbi.nlm.nih.gov/pubmed/26152007", "http://www.ncbi.nlm.nih.gov/pubmed/26140187", "http://www.ncbi.nlm.nih.gov/pubmed/24786470", "http://www.ncbi.nlm.nih.gov/pubmed/20938838", "http://www.ncbi.nlm.nih.gov/pubmed/21075065", "http://www.ncbi.nlm.nih.gov/pubmed/18751991", "http://www.ncbi.nlm.nih.gov/pubmed/26259290", "http://www.ncbi.nlm.nih.gov/pubmed/21576416", "http://www.ncbi.nlm.nih.gov/pubmed/21686347", "http://www.ncbi.nlm.nih.gov/pubmed/23072857", "http://www.ncbi.nlm.nih.gov/pubmed/15980640", "http://www.ncbi.nlm.nih.gov/pubmed/10519426", "http://www.ncbi.nlm.nih.gov/pubmed/20482298", "http://www.ncbi.nlm.nih.gov/pubmed/18945714" ], "ideal_answer": [ "The detection of fetal RhD status can be achieved with the non-invasive method of assessing free fetal DNA in the maternal blood." ], "exact_answer": [ "free fetal DNA from maternal cirulcation" ], "type": "factoid", "id": "571366ba1174fb1755000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Determination of fetal rhesus d status by maternal plasma DNA analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24778561", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "In this study, we assessed the feasibility of fetal RhD genotyping by analysis of cell-free fetal DNA(cffDNA) extracted from plasma samples of Rhesus (Rh) D-negative pregnant women by using real-time polymerase chain reaction (PCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24778561", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1172, "text": "Performing real-time PCR on cffDNA showed accurate, efficient and reliable results, allowing rapid and high throughput non invasive determination of fetal sex and RhD status in clinical samples", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24778561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Non-invasive prenatal diagnosis of fetal RhD by using free fetal DNA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152007", "endSection": "title" }, { "offsetInBeginSection": 138, "offsetInEndSection": 311, "text": "The aim of this study is to determine fetal RhD status in the Rh incompatible pregnancies with an non-invasive technique; free fetal DNA isolation from maternal circulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152007", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1405, "text": " The detection of fetal RhD status by using a non-invasive method from maternal circulation was found to be possible. Assessing fetal RhD status non-invasively by using free fetal DNA in maternal blood will be cost-efficient, avoiding unnecessary indirect Coombs test and unnecessary Rhogam applications that is used in RH incompatible pregnancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152007", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1411, "text": "Fruitful research efforts have resulted in the clinical implementation of a number of non-invasive prenatal tests based on maternal plasma DNA analysis and included tests for fetal sex assessment, fetal rhesus D blood group genotyping and fetal chromosomal aneuploidy detection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23072857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Non-invasive antenatal diagnosis of fetal rhesus status in an alloimmunised patient.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21686347", "endSection": "title" }, { "offsetInBeginSection": 1793, "offsetInEndSection": 2230, "text": "Our subsequent investigations have shown that this elevation in fetal cell traffic may serve as an early marker for those pregnancies at risk for this disorder.A very recent exciting discovery has been that free extracellular fetal DNA can be detected in the plasma and serum of pregnant women, which may permit the rapid and accurate detection of uniquely fetal loci, such as the fetal rhesus D gene in rhesus D negative pregnant women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10985940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Fetal rhesus D (RhD) status determination using circulating cell-free fetal DNA from maternal plasma or serum is now recognized in Europe as a reliable and useful tool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22386678", "endSection": "abstract" }, { "offsetInBeginSection": 921, "offsetInEndSection": 1222, "text": "NGS is now sufficiently sensitive to analyze circulating fetal DNA in maternal blood (cell-free fetal DNA, cffDNA), enabling applications such as non invasive diagnosis of fetal sex (and X-linked diseases), fetal rhesus among rhesus-negative women, trisomy and, in the near future, Mendelian mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "High throughput non-invasive determination of foetal Rhesus D status using automated extraction of cell-free foetal DNA in maternal plasma and mass spectrometry", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18751991", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Non-invasive RNA-based determination of fetal Rhesus D type: a prospective study based on 96 pregnancies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10519426", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "BACKGROUND: Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024794", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1140, "text": "Fruitful research efforts have resulted in the clinical implementation of a number of non-invasive prenatal tests based on maternal plasma DNA analysis and included tests for fetal sex assessment, fetal rhesus D blood group genotyping and fetal chromosomal aneuploidy detection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23072857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": " Non-invasive prenatal diagnosis and testing by analysis of cell-free DNA in the maternal circulation is a rapidly evolving field. Current clinical applications include fetal sex determination, fetal rhesus D determination, the diagnosis of some single gene disorders, and a highly accurate screening test for aneuploidies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24786470", "endSection": "abstract" } ] }, { "body": "Which genes have been proposed as potential candidates for gene therapy of heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23281410", "http://www.ncbi.nlm.nih.gov/pubmed/24403316", "http://www.ncbi.nlm.nih.gov/pubmed/21775667", "http://www.ncbi.nlm.nih.gov/pubmed/24833660", "http://www.ncbi.nlm.nih.gov/pubmed/22558250", "http://www.ncbi.nlm.nih.gov/pubmed/22362515", "http://www.ncbi.nlm.nih.gov/pubmed/23307169", "http://www.ncbi.nlm.nih.gov/pubmed/25327883", "http://www.ncbi.nlm.nih.gov/pubmed/25023328", "http://www.ncbi.nlm.nih.gov/pubmed/22383712", "http://www.ncbi.nlm.nih.gov/pubmed/22548568", "http://www.ncbi.nlm.nih.gov/pubmed/24622121" ], "ideal_answer": [ "There are at least 6 genes which have been proposed as potential candidates of gene therapy in heart failure.\n1. Cardiac Sarco-Endoplasmic Reticulum Calcium ATPase 2A (SERCA2A)\n2. Inhibitor 1 (I-1) of Protein Phosphatase 1B\n3. Protein Phosphatase 1B (PP1B)\n4. Yes Associated Protein (YAP)\n5. Survivin\n6. S100A1" ], "exact_answer": [ [ "Sarco-Endoplasmic Reticulum Calcium ATPase 2A", "(SERCA2A)" ], [ "Inhibitor 1 of Protein Phosphatase 1B", "(I-1)" ], [ "Protein Phosphatase 1B", "(PP1B)" ], [ "Yes Associated Protein", "(YAP)" ], [ "Survivin" ], [ "S100A1" ] ], "type": "list", "id": "54c90dabf693c3b16b000004", "snippets": [ { "offsetInBeginSection": 535, "offsetInEndSection": 658, "text": "The molecular abnormalities underlying HF are discussed along with potential targets for gene therapy, focusing on SERCA2a.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25327883", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 370, "text": "The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25023328", "endSection": "abstract" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1440, "text": "In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25023328", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1462, "text": "therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24833660", "endSection": "abstract" }, { "offsetInBeginSection": 1904, "offsetInEndSection": 2024, "text": "calcium up-regulation by AAV1/SERCA2a gene therapy is safe and of potential benefit in advanced heart failure patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24622121", "endSection": "abstract" }, { "offsetInBeginSection": 1487, "offsetInEndSection": 1596, "text": "Survivin gene therapy can attenuate the progression of LV systolic dysfunction in doxorubicin cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24403316", "endSection": "abstract" }, { "offsetInBeginSection": 1959, "offsetInEndSection": 2075, "text": "Heart failure-inducible molecular targeting of PP1\u03b2 has potential as a novel therapeutic strategy for heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22558250", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 991, "text": "The recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a), along with the start of more recent phase 1 trials, opens a new era for gene therapy for the treatment of heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383712", "endSection": "abstract" }, { "offsetInBeginSection": 1746, "offsetInEndSection": 1939, "text": "Our results present a strong rationale for a clinical trial of S100A1 gene therapy for human heart failure that could potentially complement current strategies to treat end-stage heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21775667", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 558, "text": "S100A1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and animals, and myocardial-targeted S100A1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium (Ca(2+)) handling in acutely and chronically failing hearts in small animal models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21775667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "Use of gene therapy for heart failure is gaining momentum as a result of the recent successful completion of phase II of the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, which showed clinical safety and efficacy of an adeno-associated viral vector expressing sarco-endoplasmic reticulum calcium ATPase (SERCA2a).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22548568", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 921, "text": "The recent successful and safe completion of a phase 2 trial targeting the cardiac sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA2a) has the potential to open a new era for gene therapy for heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281410", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 835, "text": "The recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a) has the potential to open a new era for gene therapy in the treatment of heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23307169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "AIMS: Impaired myocardial sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) activity is a hallmark of failing hearts, and SERCA2a gene therapy improves cardiac function in animals and patients with heart failure (HF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362515", "endSection": "abstract" } ] }, { "body": "DX-88 is investigational name of which drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16916274", "http://www.ncbi.nlm.nih.gov/pubmed/19093699", "http://www.ncbi.nlm.nih.gov/pubmed/18220151", "http://www.ncbi.nlm.nih.gov/pubmed/21481442", "http://www.ncbi.nlm.nih.gov/pubmed/14572819", "http://www.ncbi.nlm.nih.gov/pubmed/21760740", "http://www.ncbi.nlm.nih.gov/pubmed/18467921", "http://www.ncbi.nlm.nih.gov/pubmed/18613770" ], "ideal_answer": [ "DX-88 is investigational name of a drug Ecallantide, a 60-amino acid recombinant protein discovered through phage display technology, that is a highly specific, potent inhibitor of human plasma kallikrein that has been used successfully in the treatment of patients experiencing acute hereditary angioedema attacks." ], "exact_answer": [ "Ecallantide" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015507" ], "type": "factoid", "id": "54f1e031c409818c32000001", "snippets": [ { "offsetInBeginSection": 505, "offsetInEndSection": 635, "text": "Ecallantide (known as DX-88 previously), a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21760740", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Ecallantide (DX-88) for acute hereditary angioedema attacks: integrated analysis of 2 double-blind, phase 3 studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21481442", "endSection": "title" }, { "offsetInBeginSection": 661, "offsetInEndSection": 992, "text": "Several novel therapies have completed phase III trials in the US, including: (i) plasma-derived C1-INH replacement therapies (Berinert P and Cinryze); (ii) a recombinant C1-INH replacement therapy (conestat alfa; Rhucin); (iii) a kallikrein inhibitor (ecallantide [DX-88]); and (iv) a bradykinin-2-receptor antagonist (icatibant).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19093699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18613770", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 403, "text": "OBJECTIVE: Ecallantide (DX-88) is a potent and specific inhibitor of plasma kallikrein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18613770", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 537, "text": "DX-88 (ecallantide), a 60-amino acid recombinant protein discovered through phage display technology, is a highly specific, potent inhibitor of human plasma kallikrein that has been used successfully in the treatment of patients experiencing acute HAE attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467921", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1204, "text": "DX-88 or ecallantide, a potent and specific inhibitor of plasma kallikrein, achieved all primary and secondary efficacy end points in a placebo-controlled, double-blind, phase 3 study, with a second phase 3 study ongoing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18220151", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 552, "text": "DX-88 (ecallantide, Dyax Corp.) is a highly specific recombinant plasma kallikrein inhibitor that halts the production of bradykinin and can be dosed subcutaneously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16916274", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 551, "text": "DX-88 (ecallantide, Dyax Corp.) is a highly specific recombinant plasma kallikrein inhibitor that halts the production of bradykinin and can be dosed subcutaneously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16916274", "endSection": "abstract" } ] }, { "body": "What type of arrhythmia is known as bidirectional ventricular tachycardia (BDVT)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14556882", "http://www.ncbi.nlm.nih.gov/pubmed/6180691", "http://www.ncbi.nlm.nih.gov/pubmed/21118730", "http://www.ncbi.nlm.nih.gov/pubmed/23094889", "http://www.ncbi.nlm.nih.gov/pubmed/19682706", "http://www.ncbi.nlm.nih.gov/pubmed/1713403", "http://www.ncbi.nlm.nih.gov/pubmed/17655675" ], "ideal_answer": [ "Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity. Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT). Based on similarity of electrocardiographic features, bidirectional ventricular tachycardia has been considered a variant of long QT syndrome. Evidence from human and animal studies attributes BVT to alternating ectopic foci originating from the distal His-Purkinje system in the left and/or right ventricle, respectively. This \"ping pong\" mechanism of reciprocating bigeminy readily produces the characteristic ECG pattern of BVT and its degeneration to polymorphic VT if additional sites develop bigeminy." ], "type": "summary", "id": "5507ea9a0195c16935000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23094889", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 572, "text": "Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity. Evidence from human and animal studies attributes BVT to alternating ectopic foci originating from the distal His-Purkinje system in the left and/or right ventricle, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118730", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1478, "text": "When the heart rate exceeded the threshold for bigeminy at the first site in the His-Purkinje system, ventricular bigeminy developed, causing the heart rate to accelerate and exceed the threshold for bigeminy at the second site. Thus, the triggered beat from the first site induced a triggered beat from the second site. The triggered beat from the second site next reciprocated by inducing a triggered beat from the first site, and so forth. Bigeminy from two sites produced BVT, and that from three or more sites produced polymorphic VT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118730", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1675, "text": "This \"ping pong\" mechanism of reciprocating bigeminy readily produces the characteristic ECG pattern of BVT and its degeneration to polymorphic VT if additional sites develop bigeminy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118730", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 603, "text": "The BVT, in this case, was most likely due to myocardial ischema. The ethiology of published BVT cases are most commonly digitalis toxicity and rarely herbal aconitine poisoning, hypokalemic periodic paralysis, cathecolaminergic VT, myocarditis, and Anderson-Tawil syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19682706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Bidirectional ventricular tachycardia (BVT), although a rare arrhythmia in the general population, is frequently observed in patients with Andersen-Tawil syndrome and long QT interval. However, the pharmacologic treatment of this arrhythmia remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17655675", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1214, "text": "This report suggests that flecainide can be effective in controlling BVT associated with Andersen-Tawil syndrome and indicates that the left ventricular dysfunction is secondary to the arrhythmia and not due to an associated phenotypic manifestation of the disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17655675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Based on similarity of electrocardiographic features, bidirectional ventricular tachycardia has been considered a variant of long QT syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14556882", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 896, "text": "Double ventricular ectopic rhythms had bizarre abnormal QRS complexes of two different morphologies and were inscribed in opposite directions. Ectopic rhythms in each case had parasystolic characteristics. These observations suggest bifocal automaticity as a mechanism for bidirectional ventricular tachycardia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1713403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "Bidirectional ventricular tachycardia, defined as the rapid alternation of the QRS complexes with successive opposing axial deviation, is a rare arrhythmia. In the rare cases which have undergone endocavitary investigations, an infrahisian origin has generally been proved. However, the mechanism of these tachycardias remains poorly understood and is discussed with respect to a new case.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6180691", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1703, "text": "In the light of previously reported cases with documented endocavitary investigation and this new case, it seems possible to talk in terms of true \"bidirectional ventricular tachycardia\", a tachycardia whose mechanism is obscure but certainly not univocal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6180691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23094889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "BACKGROUND: Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23094889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Bidirectional ventricular tachycardia, defined as the rapid alternation of the QRS complexes with successive opposing axial deviation, is a rare arrhythmia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6180691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23094889", "endSection": "abstract" } ] }, { "body": "Which genes have been found to be associated with restless leg syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21572129", "http://www.ncbi.nlm.nih.gov/pubmed/18032746", "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "http://www.ncbi.nlm.nih.gov/pubmed/21287604", "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "http://www.ncbi.nlm.nih.gov/pubmed/23227859" ], "ideal_answer": [ "Human L-Ferritin\nThe genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes\nHomozygosity for the T-allele of BTBD9 rs9296249\nMEIS1\nIntragenic guanosine triphosphate cyclohydrolase-1 duplication\nLRRK2 gene mutation" ], "exact_answer": [ [ "LRRK2 gene mutation" ], [ "Human L-Ferritin" ], [ "The genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes" ], [ "Homozygosity for the T-allele of BTBD9 rs9296249" ], [ "MEIS1" ], [ "Intragenic guanosine triphosphate cyclohydrolase-1 duplication" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012148" ], "type": "list", "id": "52f8995b2059c6d71c00004a", "snippets": [ { "offsetInBeginSection": 438, "offsetInEndSection": 644, "text": "We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 606, "text": "The genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes that have been previously associated with iron status and/or restless leg syndrome (RLS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "endSection": "abstract" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1005, "text": "Homozygosity for the T-allele of BTBD9 rs9296249 was associated with lower serum ferritin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1371, "text": "A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "endSection": "abstract" }, { "offsetInBeginSection": 1088, "offsetInEndSection": 1296, "text": " In the German sample, variants in MEIS1 and BTBD9 were associated with RLS in ESRD (P(nom)\u22640.004, ORs 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21572129", "endSection": "abstract" }, { "offsetInBeginSection": 1482, "offsetInEndSection": 1604, "text": " This is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21572129", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 781, "text": "Four family members developed dopa-responsive dystonia, with onset in their late teens, and subsequently developed restless leg syndrome and migraine. CONCLUSIONS: This is the first report of an intragenic guanosine triphosphate cyclohydrolase-1 duplication in a dopa-responsive dystonia family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21287604", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 335, "text": "To date, no gene mutation has been found, but five gene loci have been mapped in primary RLS to chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1 through 5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18032746", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1614, "text": "We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our family with a rather homogeneous phenotype and very early disease onset represents a unique opportunity to further elucidate the genetic causes of the frequent restless leg syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18032746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "A case of restless leg syndrome in a family with LRRK2 gene mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227859", "endSection": "title" }, { "offsetInBeginSection": 791, "offsetInEndSection": 938, "text": "The association between RLS and LRRK2 gene mutation may be casual, but it can hypothesized that RLS is a possible phenotypic presentation in PARK8.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227859", "endSection": "abstract" } ] }, { "body": "Is the circadian clock involved in ribosome biogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23300384" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18469688", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18451217", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18463493", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18448084", "o": "D057906" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18463494", "o": "D057906" } ], "ideal_answer": [ "Yes. The circadian clock coordinates ribosome biogenesis. It influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0042254", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057906" ], "type": "yesno", "id": "56bf7d90ef6e394741000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "The circadian clock coordinates ribosome biogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300384", "endSection": "title" }, { "offsetInBeginSection": 276, "offsetInEndSection": 917, "text": "Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300384", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 668, "text": "Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "The circadian clock coordinates ribosome biogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300384", "endSection": "title" }, { "offsetInBeginSection": 276, "offsetInEndSection": 381, "text": "Here we show that the circadian clock exerts its function also through the regulation of mRNA translation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300384", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 670, "text": "Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300384", "endSection": "abstract" } ] }, { "body": "Can mutations in Calmodulin cause ventricular fibrillation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24076290", "http://www.ncbi.nlm.nih.gov/pubmed/11807557" ], "ideal_answer": [ "Yes, mutations in CALM underly IVF manifesting in childhood and adolescence." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/CALM_PARTE", "http://www.uniprot.org/uniprot/CALM_LUMRU", "http://www.uniprot.org/uniprot/CALM_ANAPL", "http://www.uniprot.org/uniprot/CALM_PNECA", "http://www.uniprot.org/uniprot/CALM_BRYDI", "http://www.uniprot.org/uniprot/CALM_PFIPI", "http://www.uniprot.org/uniprot/CALM_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016277", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016278", "http://www.uniprot.org/uniprot/CALM_EMENI", "http://www.uniprot.org/uniprot/CALM_FAGSY", "http://www.uniprot.org/uniprot/CALM_PLEOS", "http://www.uniprot.org/uniprot/CALM_DANRE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014693", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002147", "http://www.uniprot.org/uniprot/CALM_MAIZE", "http://www.uniprot.org/uniprot/CALM_HALOK", "http://www.uniprot.org/uniprot/CALM_ASPOR", "http://www.uniprot.org/uniprot/CALM_HORVU", "http://www.uniprot.org/uniprot/CALM_CTEID", "http://www.uniprot.org/uniprot/CALM_SOLLC", "http://www.uniprot.org/uniprot/CALM_CIOIN", "http://www.uniprot.org/uniprot/CALM_METSE", "http://www.uniprot.org/uniprot/CALM_BOVIN", "http://www.uniprot.org/uniprot/CALM_STIJA", "http://www.uniprot.org/uniprot/CALM_OREMO", "http://www.uniprot.org/uniprot/CALM_LOCMI", "http://www.uniprot.org/uniprot/CALM_SCHPO", "http://www.uniprot.org/uniprot/CALM_TRYCR", "http://www.uniprot.org/uniprot/CALM_XENLA", "http://www.uniprot.org/uniprot/CALM_DROME", "http://www.uniprot.org/uniprot/CALM_WHEAT", "http://www.uniprot.org/uniprot/CALM_PHYPO", "http://www.uniprot.org/uniprot/CALM_CHLRE", "http://www.uniprot.org/uniprot/CALM_HUMAN", "http://www.uniprot.org/uniprot/CALM_SACJA", "http://www.uniprot.org/uniprot/CALM_PYTSP", "http://www.uniprot.org/uniprot/CALM_PAXIN", "http://www.uniprot.org/uniprot/CALM_TETPY", "http://www.uniprot.org/uniprot/CALM_ONCSP", "http://www.uniprot.org/uniprot/CALM_TRYBG", "http://www.uniprot.org/uniprot/CALM_TRYBB", "http://www.uniprot.org/uniprot/CALM_PATSP", "http://www.uniprot.org/uniprot/CALM_BLAEM", "http://www.uniprot.org/uniprot/CALM_TORCA", "http://www.uniprot.org/uniprot/CALM_EUPCH", "http://www.uniprot.org/uniprot/CALM_MALDO", "http://www.uniprot.org/uniprot/CALM_HELAN", "http://www.uniprot.org/uniprot/CALM_EPIAK", "http://www.uniprot.org/uniprot/CALM_PYUSP", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016276", "http://www.uniprot.org/uniprot/CALM_ALEFU", "http://www.uniprot.org/uniprot/CALM_MACPY", "http://www.uniprot.org/uniprot/CALM_SPIOL", "http://www.uniprot.org/uniprot/CALM_CAEEL", "http://www.uniprot.org/uniprot/CALM_HETTR", "http://www.uniprot.org/uniprot/CALM_APLCA", "http://www.uniprot.org/uniprot/CALM_PHYIN", "http://www.uniprot.org/uniprot/CALM_ELEEL", "http://www.uniprot.org/uniprot/CALM_STRPU", "http://www.uniprot.org/uniprot/CALM_MAGO7", "http://www.uniprot.org/uniprot/CALM_PLECO", "http://www.uniprot.org/uniprot/CALM_PERFV", "http://www.uniprot.org/uniprot/CALM_YEAST", "http://www.uniprot.org/uniprot/CALM_KLULA", "http://www.uniprot.org/uniprot/CALM_COLTR", "http://www.uniprot.org/uniprot/CALM_RABIT", "http://www.uniprot.org/uniprot/CALM_DICDI", "http://www.uniprot.org/uniprot/CALM_MYXGL", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018497", "http://www.uniprot.org/uniprot/CALM_EUGGR", "http://www.uniprot.org/uniprot/CALM_PONAB", "http://www.uniprot.org/uniprot/CALM_STYLE", "http://www.uniprot.org/uniprot/CALM_KARMI", "http://www.uniprot.org/uniprot/CALM_RAT", "http://www.uniprot.org/uniprot/CALM_PLAFA", "http://www.uniprot.org/uniprot/CALM_TETTH", "http://www.uniprot.org/uniprot/CALM_AGABI", "http://www.uniprot.org/uniprot/CALM_STRIE", "http://www.uniprot.org/uniprot/CALM_AJECG", "http://www.uniprot.org/uniprot/CALM_MOUSC", "http://www.uniprot.org/uniprot/CALM_GECJA", "http://www.uniprot.org/uniprot/CALM_SUBDO", "http://www.uniprot.org/uniprot/CALM_PROMN", "http://www.uniprot.org/uniprot/CALM_CANAX", "http://www.uniprot.org/uniprot/CALM_CHICK", "http://www.uniprot.org/uniprot/CALM_COLGL", "http://www.uniprot.org/uniprot/CALM_PLAF7", "http://www.uniprot.org/uniprot/CALM_LILLO", "http://www.uniprot.org/uniprot/CALM_NEUCR", "http://www.uniprot.org/uniprot/CALM_RENRE", "http://www.uniprot.org/uniprot/CALM_MOUSE", "http://www.uniprot.org/uniprot/CALM_ACHKL", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018487", "http://www.uniprot.org/uniprot/CALM_LYTPI", "http://www.uniprot.org/uniprot/CALM_MEDSA", "http://www.uniprot.org/uniprot/CALM_CAPAN" ], "type": "yesno", "id": "52b2f0864003448f55000007", "snippets": [ { "offsetInBeginSection": 648, "offsetInEndSection": 1613, "text": "We characterized a family presenting with a history of ventricular fibrillation (VF) and sudden death without ECG or echocardiographic abnormalities at rest. Two siblings died suddenly at the ages of 9 and 10 years, and another two were resuscitated from out-of-hospital cardiac arrest with documented VF at age 10 and 16, respectively. Exome sequencing identified a missense mutation affecting a highly conserved residue (p.Phe90Leu) in the CALM1 gene encoding calmodulin. This mutation was also carried by one of the sibs who died suddenly, for whom DNA was available. The mutation was present in the mother and in an sibling, both asymptomatic but displaying a marginally prolonged QT-interval during exercise. CONCLUSIONS: We identified a mutation in CALM1 underlying IVF manifesting in childhood and adolescence. The causality of the mutation is supported by previous studies demonstrating that Phe90 mediates the direct interaction of CaM with target peptides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24076290", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 917, "text": "Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11807557", "endSection": "abstract" } ] }, { "body": "Do the Sleeping Beauty or the piggyBac transposons have higher transposition efficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24928388", "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "http://www.ncbi.nlm.nih.gov/pubmed/17164785", "http://www.ncbi.nlm.nih.gov/pubmed/21516337", "http://www.ncbi.nlm.nih.gov/pubmed/17005721", "http://www.ncbi.nlm.nih.gov/pubmed/20606646" ], "ideal_answer": [ "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies." ], "exact_answer": [ "piggyBac" ], "type": "factoid", "id": "56c4d14ab04e159d0e000003", "snippets": [ { "offsetInBeginSection": 402, "offsetInEndSection": 642, "text": "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 458, "text": "We found that PB demonstrated the highest efficiency of stable gene transfer in PBL-derived T cells, whereas SB11 and Tol2 mediated intermediate and lowest efficiencies, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20606646", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 620, "text": "However, recently another system known as PiggyBac (PB) has been introduced and developed for fulfilling the same purposes, for example, mutagenesis, transgenesis and gene therapy and in some cases with improved transposition efficiency and advantages over the Sleeping Beauty transposon system, although improved hyperactive transposase has highly increased the transposition efficacy for SB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21516337", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 642, "text": "Here, we compared the efficiency of two different transposon systems, Sleeping Beauty (SB) and piggyBac (PB), for the generation of murine iPS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24928388", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 1011, "text": "However, recently another system known as PiggyBac (PB) has been introduced and developed for fulfilling the same purposes, for example, mutagenesis, transgenesis and gene therapy and in some cases with improved transposition efficiency and advantages over the Sleeping Beauty transposon system, although improved hyperactive transposase has highly increased the transposition efficacy for SB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21516337", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 878, "text": "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 458, "text": "In this study, we compared the genomic integration efficiencies and transposition site preferences of Sleeping Beauty (SB or SB11), Tol2, and piggyBac (PB) transposon systems in primary T cells derived from peripheral blood lymphocytes (PBL) and umbilical cord blood (UCB). We found that PB demonstrated the highest efficiency of stable gene transfer in PBL-derived T cells, whereas SB11 and Tol2 mediated intermediate and lowest efficiencies, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20606646", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 875, "text": "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis. Although Sleeping Beauty had no detectable genomic bias with respect to insertions in genes or intergenic regions, both Sleeping Beauty and PiggyBac transposons displayed preferential integration into actively transcribed loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 647, "text": "We have compared the chromosomal mobilization efficiency and insertion site preference of the two transposons mobilized from the same donor site in mouse embryonic stem (ES) cells under conditions in which there were no selective constraints on the transposons' insertion sites. Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies, no evidence for local hopping and a significant bias toward reintegration in intragenic regions, which demonstrate its utility for insertional mutagenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 427, "text": "In this study we directly compared the genomic integration efficiencies of piggyBac, hyperactive Sleeping Beauty (SB11), Tol2, and Mos1 in four mammalian cell lines. piggyBac demonstrated significantly higher transposition activity in all cell lines whereas Mos1 had no activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17005721", "endSection": "abstract" } ] }, { "body": "Where does TORC1 sequester during heat stress?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22727621" ], "ideal_answer": [ "Upon heat stress, TORC1 is recruited to stress granules." ], "type": "summary", "id": "56cdf4fe5795f9a73e000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Transient sequestration of TORC1 into stress granules during heat stress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "title" }, { "offsetInBeginSection": 240, "offsetInEndSection": 537, "text": "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 705, "text": "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 872, "text": "TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 869, "text": "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 536, "text": "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 707, "text": "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling. Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 707, "text": "Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling. Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 539, "text": "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 874, "text": "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress. Moreover, TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 390, "text": "Although TORC1 signaling is repressed by various stresses in yeast, the underlying mechanisms remain elusive. Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 390, "text": "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 707, "text": "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract" } ] }, { "body": "Is rivaroxaban metabolized in kidneys?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23026665", "http://www.ncbi.nlm.nih.gov/pubmed/23631188", "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "http://www.ncbi.nlm.nih.gov/pubmed/22931521", "http://www.ncbi.nlm.nih.gov/pubmed/19712596", "http://www.ncbi.nlm.nih.gov/pubmed/19196845", "http://www.ncbi.nlm.nih.gov/pubmed/23652451", "http://www.ncbi.nlm.nih.gov/pubmed/22825670", "http://www.ncbi.nlm.nih.gov/pubmed/23790601" ], "ideal_answer": [ "rivaroxaban undergoes renal metabolism" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007668", "http://www.biosemantics.org/jochem#4243836" ], "type": "yesno", "id": "532f09d2d6d3ac6a3400002b", "snippets": [ { "offsetInBeginSection": 430, "offsetInEndSection": 636, "text": "The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23790601", "endSection": "abstract" }, { "offsetInBeginSection": 1473, "offsetInEndSection": 1614, "text": "The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652451", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 661, "text": "Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23631188", "endSection": "abstract" }, { "offsetInBeginSection": 1115, "offsetInEndSection": 1268, "text": "In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026665", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1135, "text": "Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22931521", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 800, "text": "However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22825670", "endSection": "abstract" }, { "offsetInBeginSection": 1665, "offsetInEndSection": 1776, "text": "Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "endSection": "abstract" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1496, "text": "Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. 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In horses some passage of semifluid fecal material, intermittent penile relaxation, and mild sedation has been described. 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These included most notably fatigue, lightheadedness, nausea and vomiting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16379031", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 284, "text": "The nalmefene treated group ate 22% less, both in terms of absolute weight and caloric intake, of a standardised buffet-meal than did the placebo group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2315439", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 1030, "text": "Thus the apparent nutrient specificity of nalmefene appeared to be an indirect consequence of its effect on palatability. Nalmefene also caused slight increases in self-rated alertness, and decreases in ratings of tiredness and elation, although it was thought unlikely that these accounted for observed changes in eating behaviour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2315439", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1554, "text": "In the second study, six healthy men were initially administered a single 50-mg dose of drug, and plasma samples were obtained at selected time intervals for 48 hours. A dosing schedule of 20 mg q12h was then started and continued for seven days. Plasma samples were collected immediately before each dose and at selected times for up to 48 hours after the last dose. The drug was well tolerated by all subjects, and no clinically significant adverse effects were observed during the seven-day administration period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3680580", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 524, "text": " In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as lightheadedness, at the higher doses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3680580", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1350, "text": "Doses of nalmefene as large as 0.4 mg/kg, IV, produced only minor side effects. These side effects included some passage of semifluid fecal material, intermittent penile relaxation, and mild sedation. Treated horses responded normally to external stimuli, retained their appetites, and performed appropriately when ridden. Sedation wore off during the course of prolonged infusions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3826875", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 397, "text": "The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3943269", "endSection": "abstract" } ] }, { "body": "Is Hirschsprung disease one of the characteristics of the Mowat-Wilson syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "http://www.ncbi.nlm.nih.gov/pubmed/24092421", "http://www.ncbi.nlm.nih.gov/pubmed/16088920", "http://www.ncbi.nlm.nih.gov/pubmed/24029077", "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "http://www.ncbi.nlm.nih.gov/pubmed/23610866", "http://www.ncbi.nlm.nih.gov/pubmed/21957361", "http://www.ncbi.nlm.nih.gov/pubmed/16150342", "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "http://www.ncbi.nlm.nih.gov/pubmed/19302864", "http://www.ncbi.nlm.nih.gov/pubmed/20158378", "http://www.ncbi.nlm.nih.gov/pubmed/11891681", "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "http://www.ncbi.nlm.nih.gov/pubmed/20145308", "http://www.ncbi.nlm.nih.gov/pubmed/23427518" ], "ideal_answer": [ "Mowat-Wilson syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects.", "Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprung s disease, intellectual disability, and prominent facial features are present ", "Yes. Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprungs disease, intellectual disability, and prominent facial features are present" ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10487", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627" ], "type": "yesno", "id": "55001420e9bde69634000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprung's disease, intellectual disability, and prominent facial features are present", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24092421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Individuals with Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Mowat-Wilson syndrome is a genetic disease characterized by typical facial features, Hirschsprung disease and multiple congenital abnormalities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23610866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 591, "text": " The prevalence of Mowat-Wilson syndrome is currently unknown, but it seems that Mowat-Wilson syndrome is underdiagnosed, particularly in patients without Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "\"Mowat-Wilson\" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11891681", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation; a multiple congenital anomaly syndrome characterised by a typical facial gestalt, Hirschsprung disease or severe constipation, genitourinary anomaly, congenital heart defects, agenesis of corpus callosum and eye defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND/PURPOSE: Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16150342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Severe clinical course of Hirschsprung disease in a Mowat-Wilson syndrome patient.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20145308", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 756, "text": "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 421, "text": "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Mowat-Wilson syndrome is a genetic disease characterized by typical facial features, Hirschsprung disease and multiple congenital abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23610866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Supernumerary intestinal muscle coat in a patient with Hirschsprung disease/Mowat-Wilson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20158378", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "We present the 1st case report of an additional enteric smooth muscle layer in a patient with Mowat-Wilson syndrome and Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20158378", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 205, "text": "Mowat-Wilson\" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11891681", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16088920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Mowat-Wilson syndrome is a genetic disorder characterized by a distinct facial appearance, moderate-to-severe mental retardation, microcephaly, agenesis of the corpus callosum, Hirschsprung disease, congenital heart disease, and genital anomalies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "We present the 1st case report of an additional enteric smooth muscle layer in a patient with Mowat-Wilson syndrome and Hirschsprung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20158378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16088920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Outcomes of Hirschsprung's disease associated with Mowat-Wilson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19302864", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 420, "text": "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "endSection": "abstract" } ] }, { "body": "Which are the most common methods for gene prioritization analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24260251", "http://www.ncbi.nlm.nih.gov/pubmed/23028459", "http://www.ncbi.nlm.nih.gov/pubmed/23434623", "http://www.ncbi.nlm.nih.gov/pubmed/17646288", "http://www.ncbi.nlm.nih.gov/pubmed/24110485", "http://www.ncbi.nlm.nih.gov/pubmed/23855662", "http://www.ncbi.nlm.nih.gov/pubmed/23185389", "http://www.ncbi.nlm.nih.gov/pubmed/22719993", "http://www.ncbi.nlm.nih.gov/pubmed/24219996", "http://www.ncbi.nlm.nih.gov/pubmed/18508807", "http://www.ncbi.nlm.nih.gov/pubmed/19346957", "http://www.ncbi.nlm.nih.gov/pubmed/21602267", "http://www.ncbi.nlm.nih.gov/pubmed/17267438", "http://www.ncbi.nlm.nih.gov/pubmed/20840752", "http://www.ncbi.nlm.nih.gov/pubmed/21731658", "http://www.ncbi.nlm.nih.gov/pubmed/20823322", "http://www.ncbi.nlm.nih.gov/pubmed/19465376", "http://www.ncbi.nlm.nih.gov/pubmed/21609954", "http://www.ncbi.nlm.nih.gov/pubmed/21668950", "http://www.ncbi.nlm.nih.gov/pubmed/22570409", "http://www.ncbi.nlm.nih.gov/pubmed/23696895", "http://www.ncbi.nlm.nih.gov/pubmed/16680138", "http://www.ncbi.nlm.nih.gov/pubmed/17939863", "http://www.ncbi.nlm.nih.gov/pubmed/20576703", "http://www.ncbi.nlm.nih.gov/pubmed/23633938", "http://www.ncbi.nlm.nih.gov/pubmed/22430954", "http://www.ncbi.nlm.nih.gov/pubmed/19602527", "http://www.ncbi.nlm.nih.gov/pubmed/21699738", "http://www.ncbi.nlm.nih.gov/pubmed/20823330", "http://www.ncbi.nlm.nih.gov/pubmed/22654636", "http://www.ncbi.nlm.nih.gov/pubmed/18689812", "http://www.ncbi.nlm.nih.gov/pubmed/22808075", "http://www.ncbi.nlm.nih.gov/pubmed/20074336", "http://www.ncbi.nlm.nih.gov/pubmed/22893106", "http://www.ncbi.nlm.nih.gov/pubmed/18433471" ], "ideal_answer": [ "Functional annotation-based approaches and literature-based approaches have been initially used. In recent years, network-based methods - which utilize a knowledge network derived from biological knowledge - have been utilized for gene prioritization. Currently network-based methods are the ones most widely used." ], "exact_answer": [ [ "network-based methods" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "list", "id": "530cf4d5e2bfff940c000004", "snippets": [ { "offsetInBeginSection": 587, "offsetInEndSection": 750, "text": "We developed a new network inference algorithm called the Knowledge Network Gene Prioritization (KNGP) algorithm which can incorporate both link and node knowledge", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260251", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 320, "text": " In recent years, network-based methods - which utilize a knowledge network derived from biological knowledge - have been utilized for gene prioritization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260251", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 349, "text": "We describe a bioinformatics approach, together with a freely accessible, interactive and flexible software termed Endeavour, to prioritize candidate genes underlying biological processes or diseases, based on their similarity to known genes involved in these phenomena", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16680138", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 276, "text": " We intend to use the ensemble boosting learning techniques to combine variant computational approaches for gene prioritization in order to improve the overall performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24110485", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 977, "text": "The experimental results show that our ensemble learning approach outperforms the four gene-prioritization methods in ToppGene suite in the ranking results of the 13 known genes in terms of mean average precision, ROC and AUC measures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24110485", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 700, "text": "The proposed enhanced RaJoLink rare-term model combines text mining and gene prioritization approaches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23855662", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 482, "text": " Computational gene prioritization is based on various pieces of correlative evidence that associate each gene with the given disease and suggest possible causal links", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633938", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 356, "text": "Recently, many network-based methods have been proposed that implicitly utilize the modularity principle, which states that genes causing the same or similar diseases tend to form physical or functional modules in gene/protein relationship networks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23434623", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 558, "text": "the random walk with restart (RWR) algorithm is considered to be a state-of-the-art approach, but the modularity principle has not been fully considered in traditional RWR approaches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23434623", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 780, "text": "Therefore, we propose a novel method called ORIENT (neighbor-favoring weight reinforcement) to improve the performance of RWR through proper intensification of the weights of interactions close to the known disease genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23434623", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 374, "text": "Network-based methods have been successfully exploiting this concept by capturing the interaction of genes or proteins into a score", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185389", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 524, "text": " Over the last years, computational approaches exploiting interaction network topology have been successfully applied to prioritize individual genes involved in diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028459", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1034, "text": "Here, we propose a genome-wide network-based prioritization framework named GUILD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028459", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 334, "text": "The traditional approach to reduce the number of candidate genes entails fine-mapping studies using markers and pedigrees", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893106", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 809, "text": "For this purpose, we evaluate our rule-based evolutionary machine learning systems, BioHEL and GAssist, on three public microarray cancer datasets, obtaining simple rule-based models for sample classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22808075", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 646, "text": "hus, comparing the similarity between experimentally identified phenotypes and the phenotypes associated with human diseases can be used to suggest causal genes underlying a disease. In this manuscript, we present a method for disease gene prioritization based on comparing phenotypes of mouse models with those of human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22719993", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 490, "text": "We present biomarker identification problem using gene prioritization method called gene prioritization from microarray data based on shortest paths, extended with structural and biological properties and edge flux using voting scheme (GP-MIDAS-VXEF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22654636", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 96, "text": "ensemble approach to microarray data-based gene prioritization after missing value imputation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17267438", "endSection": "title" }, { "offsetInBeginSection": 699, "offsetInEndSection": 934, "text": "Recently, we have introduced the data mining tool ENDEAVOUR (Aerts et al., 2006), which performs this task automatically by relying on different genome-wide data sources, such as Gene Ontology, literature, microarray, sequence and more", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17646288", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 697, "text": "So far, biologists have relied on literature studies, extensive queries to multiple databases and hunches about expected properties of the disease gene to determine such an ordering", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17646288", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 935, "text": "We study the effect of different data integration methods, and based on the validation studies, we show that our approach, ToppGene http://toppgene.cchmc.org, outperforms two of the existing candidate gene prioritization methods, SUSPECTS and ENDEAVOU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17939863", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 682, "text": " Extending on an earlier hypothesis that the majority of genes that impact or cause disease share membership in any of several functional relationships we, for the first time, show the utility of mouse phenotype data in human disease gene prioritization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17939863", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 740, "text": "We use co-expression data from yeast (S. cerevisiae), nematode worm (C. elegans), fruit fly (D. melanogaster), mouse and human and find that the use of evolutionary conservation can indeed improve the predictive value of co-expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18433471", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 571, "text": "Using a training set of genes known to be involved in a biological process of interest, our approach consists of (i) inferring several models (based on various genomic data sources), (ii) applying each model to the candidate genes to rank those candidates against the profile of the known genes and (iii) merging the several rankings into a global ranking of the candidate genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18508807", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 105, "text": "vocabularies, representations and ranking algorithms for gene prioritization by text mining", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18689812", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 340, "text": "Recently, text mining techniques have been applied to extract prior knowledge from text-based genomic information sources and this knowledge can be used to improve the prioritization process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18689812", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 155, "text": "We present an approach to prioritize single nucleotide polymorphisms for further follow-up in genome-wide association studies of type 2 diabetes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19346957", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 483, "text": "The proposed method combines both the use of open data access from two type 2 diabetes-genome-wide association studies (granted by the Diabetes Genetics Initiative and the Welcome Trust Case Control Consortium) and the comprehensive analysis of candidate regions generated by the freely accessible ENDEAVOUR software.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19346957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19465376", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 995, "text": "The protein-protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19465376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "We present gene prioritization system (GPSy), a cross-species gene prioritization system that facilitates the arduous but critical task of prioritizing genes for follow-up functional analyses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22570409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "GPEC: a Cytoscape plug-in for random walk-based gene prioritization and biomedical evidence collection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430954", "endSection": "title" }, { "offsetInBeginSection": 156, "offsetInEndSection": 265, "text": "Among these, network-based approaches are recently proposed and outperformed functional annotation-based ones", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430954", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 592, "text": "In the plug-in, gene prioritization is performed through a random walk with restart algorithm, a state-of-the art network-based method, along with a gene/protein relationship networ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430954", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 772, "text": "Here we present a multi-dimensional evidence-based candidate gene prioritization approach for complex diseases and demonstrate it in schizophrenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19602527", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 839, "text": "We present a multi-view approach to retrieve biomedical knowledge using different controlled vocabularies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074336", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 336, "text": "Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20576703", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 212, "text": "Genomic linkage and association studies are commonly performed for identifying disease-related gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20823322", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 641, "text": "Here, we introduce MedSim, a novel approach for ranking candidate genes for a particular disease based on functional comparisons involving the Gene Ontology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20823322", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 793, "text": "MedSim uses functional annotations of known disease genes for assessing the similarity of diseases as well as the disease relevance of candidate genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20823322", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 914, "text": "Here, we report a large-scale analysis of spatial, i.e. 3D, gene-expression data from an entire organ (the mouse brain) for the purpose of evaluating and ranking positional candidate genes, showing that the spatial gene-expression patterns can be successfully exploited for the prediction of gene-phenotype associations not only for mouse phenotypes, but also for human central nervous system-related Mendelian disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20823330", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 533, "text": "In this paper, we propose an expandable framework for gene prioritization that can integrate multiple heterogeneous data sources by taking advantage of a unified graphic representation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21731658", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 828, "text": "We demonstrate that existing methods are likely to favor highly connected genes, making prioritization sensitive to the skewed degree distribution of PPI networks, as well as ascertainment bias in available interaction and disease association data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21699738", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1058, "text": "Motivated by this observation, we propose several statistical adjustment methods to account for the degree distribution of known disease and candidate genes, using a PPI network with associated confidence scores for interactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21699738", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 645, "text": "Here we employ a previously described method of candidate gene prioritization based mainly on gene annotation, in accompaniment with a technique based on the evaluation of pertinent sequence motifs or signatures, in an attempt to refine the gene prioritization approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21668950", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 603, "text": "We introduce the novel G\u00e9nie algorithm that overcomes these problems by evaluating the literature attached to all genes in a genome and to their orthologs according to a selected topic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21609954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "PINTA (available at http://www.esat.kuleuven.be/pinta/; this web site is free and open to all users and there is no login requirement) is a web resource for the prioritization of candidate genes based on the differential expression of their neighborhood in a genome-wide protein-protein interaction network", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21602267", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 582, "text": "We have recently developed a computational method for constitutional genetic disorders that identifies the most promising candidate genes by replacing prior knowledge by experimental data of differential gene expression between affected and healthy individual", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840752", "endSection": "abstract" } ] }, { "body": "Which is the most common disease attributed to malfunction or absence of primary cilia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19276629", "http://www.ncbi.nlm.nih.gov/pubmed/14978161", "http://www.ncbi.nlm.nih.gov/pubmed/19186246", "http://www.ncbi.nlm.nih.gov/pubmed/14983006", "http://www.ncbi.nlm.nih.gov/pubmed/21439862", "http://www.ncbi.nlm.nih.gov/pubmed/18407555", "http://www.ncbi.nlm.nih.gov/pubmed/23124509", "http://www.ncbi.nlm.nih.gov/pubmed/18694559", "http://www.ncbi.nlm.nih.gov/pubmed/15226261", "http://www.ncbi.nlm.nih.gov/pubmed/17429051", "http://www.ncbi.nlm.nih.gov/pubmed/19273592" ], "ideal_answer": [ "When ciliary function is perturbed, photoreceptors may die, kidney tubules develop cysts, limb digits multiply and brains form improperly. Mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease. Malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD)." ], "exact_answer": [ "Polycystic kidney disease (PKD)" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031514", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0035058", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031512", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031513" ], "type": "factoid", "id": "513ce494bee46bd34c000009", "snippets": [ { "offsetInBeginSection": 81, "offsetInEndSection": 150, "text": "role of primary cilia in autosomal dominant polycystic kidney disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439862", "endSection": "title" }, { "offsetInBeginSection": 310, "offsetInEndSection": 424, "text": "Recent research has focused on defects in signaling mediated by the primary cilia as the causative factor in ADPKD", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439862", "endSection": "sections.0" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1377, "text": "Interestingly, primary cilia concentrate p75NTR receptors in their membranes and are abnormally structured/damaged in transgenic (Tg) AD\u2011model mice, which could impact on the adult neurogenesis occurring in the dentate gyrus's subgranular zone (SGZ) that is necessary for new memory encoding, thereby favouring typical AD cognitive decline", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124509", "endSection": "sections.0" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1207, "text": "malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276629", "endSection": "sections.0" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1462, "text": "While PKD was one of the first diseases to be linked to dysfunctional primary cilia, defects in this organelle have subsequently been associated with many other phenotypes, including cancer, obesity, diabetes as well as a number of developmental defects", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276629", "endSection": "sections.0" }, { "offsetInBeginSection": 147, "offsetInEndSection": 327, "text": "mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19273592", "endSection": "sections.0" }, { "offsetInBeginSection": 460, "offsetInEndSection": 578, "text": "Although Glis3(zf/zf) mice form normal primary cilia, renal cysts contain relatively fewer cells with a primary cilium", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19273592", "endSection": "sections.0" }, { "offsetInBeginSection": 470, "offsetInEndSection": 608, "text": "When ciliary function is perturbed, photoreceptors may die, kidney tubules develop cysts, limb digits multiply and brains form improperly.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19186246", "endSection": "sections.0" }, { "offsetInBeginSection": 306, "offsetInEndSection": 421, "text": "Here, we report that CP110 interacts with CEP290--a protein whose deficiency is implicated in human ciliary disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18694559", "endSection": "sections.0" }, { "offsetInBeginSection": 523, "offsetInEndSection": 640, "text": "The cholangiociliopathies include but are not limited to cystic and fibrotic liver diseases associated with mutations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18407555", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Cysts in the kidney are among the most common inherited human pathologies, and recent research has uncovered that a defect in cilia-mediated signaling activity is a key factor that leads to cyst formation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17429051", "endSection": "sections.0" }, { "offsetInBeginSection": 301, "offsetInEndSection": 452, "text": "Multiple proteins whose functions are disrupted in cystic diseases have now been localized to the cilium or at the basal body at the base of the cilium", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17429051", "endSection": "sections.0" }, { "offsetInBeginSection": 691, "offsetInEndSection": 822, "text": "Polaris has been shown to co-localize with primary cilia, and these structures have been implicated in the formation of renal cysts", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226261", "endSection": "sections.0" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1245, "text": "hus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226261", "endSection": "sections.0" }, { "offsetInBeginSection": 766, "offsetInEndSection": 948, "text": "In cultured renal cells, the PKHD1 gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2, at the basal bodies of primary cilia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14983006", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14983006", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The autosomal recessive polycystic kidney disease protein is localized to primary cilia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14978161", "endSection": "title" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1213, "text": "It is proposed that the pathogenesis of autosomal recessive polycystic kidney disease is linked to the dysfunction of primary cilia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14978161", "endSection": "sections.0" } ] }, { "body": "What is the usefulness of ultraconserved elements in phylogeny?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22593086", "http://www.ncbi.nlm.nih.gov/pubmed/23824177", "http://www.ncbi.nlm.nih.gov/pubmed/23382987", "http://www.ncbi.nlm.nih.gov/pubmed/24021724", "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "http://www.ncbi.nlm.nih.gov/pubmed/22232343" ], "ideal_answer": [ "Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales", "Ultraconserved elements and their flanking DNA are novel phylogenomic markers that resolve placental mammal phylogeny when combined with species-tree analysis. Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010802" ], "type": "summary", "id": "553cf397f321868558000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Target capture and massively parallel sequencing of ultraconserved elements for comparative studies at shallow evolutionary time scales", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24021724", "endSection": "title" }, { "offsetInBeginSection": 267, "offsetInEndSection": 409, "text": "Here, we evaluate the efficacy of genomic markers targeting ultraconserved DNA elements (UCEs) for analyses at shallow evolutionary timescales", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24021724", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1558, "text": "Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24021724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "A Phylogenomic Perspective on the Radiation of Ray-Finned Fishes Based upon Targeted Sequencing of Ultraconserved Elements (UCEs)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23824177", "endSection": "title" }, { "offsetInBeginSection": 489, "offsetInEndSection": 1393, "text": "Here, we provide a genomic perspective on longstanding questions regarding the diversification of major groups of ray-finned fishes through targeted enrichment of ultraconserved nuclear DNA elements (UCEs) and their flanking sequence. Our workflow efficiently and economically generates data sets that are orders of magnitude larger than those produced by traditional approaches and is well-suited to working with museum specimens. Analysis of the UCE data set recovers a well-supported phylogeny at both shallow and deep time-scales that supports a monophyletic relationship between Amia and Lepisosteus (Holostei) and reveals elopomorphs and then osteoglossomorphs to be the earliest diverging teleost lineages. Our approach additionally reveals that sequence capture of UCE regions and their flanking sequence offers enormous potential for resolving phylogenetic relationships within ray-finned fishes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23824177", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 555, "text": "We applied a new phylogenomic approach to resolve relationships in Neoaves using target enrichment (sequence capture) and high-throughput sequencing of ultraconserved elements (UCEs) in avian genomes. We collected sequence data from UCE loci for 32 members of Neoaves and one outgroup (chicken) and analyzed data sets that differed in their amount of missing data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382987", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "More than 1000 ultraconserved elements provide evidence that turtles are the sister group of archosaurs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22593086", "endSection": "title" }, { "offsetInBeginSection": 429, "offsetInEndSection": 1021, "text": "A recent analysis of shared microRNA families found that turtles are more closely related to lepidosaurs. To test this hypothesis with data from many single-copy nuclear loci dispersed throughout the genome, we used sequence capture, high-throughput sequencing and published genomes to obtain sequences from 1145 ultraconserved elements (UCEs) and their variable flanking DNA. The resulting phylogeny provides overwhelming support for the hypothesis that turtles evolved from a common ancestor of birds and crocodilians, rejecting the hypothesized relationship between turtles and lepidosaurs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22593086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Ultraconserved elements anchor thousands of genetic markers spanning multiple evolutionary timescales", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232343", "endSection": "title" }, { "offsetInBeginSection": 359, "offsetInEndSection": 1449, "text": "We introduce a new class of molecular marker, anchored by ultraconserved genomic elements (UCEs), that universally enable target enrichment and sequencing of thousands of orthologous loci across species separated by hundreds of millions of years of evolution. Our analyses here focus on use of UCE markers in Amniota because UCEs and phylogenetic relationships are well-known in some amniotes. We perform an in silico experiment to demonstrate that sequence flanking 2030 UCEs contains information sufficient to enable unambiguous recovery of the established primate phylogeny. We extend this experiment by performing an in vitro enrichment of 2386 UCE-anchored loci from nine, non-model avian species. We then use alignments of 854 of these loci to unambiguously recover the established evolutionary relationships within and among three ancient bird lineages. Because many organismal lineages have UCEs, this type of genetic marker and the analytical framework we outline can be applied across the tree of life, potentially reshaping our understanding of phylogeny at many taxonomic levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Ultraconserved elements are novel phylogenomic markers that resolve placental mammal phylogeny when combined with species-tree analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 571, "text": "we outline a phylogenomic approach using a novel class of phylogenetic markers derived from ultraconserved elements and flanking DNA. Using species-tree analysis that accounts for discord among hundreds of independent loci, we show that this class of marker is useful for recovering deep-level phylogeny in placental mammals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1802, "text": "One of the most remarkable findings of our study is that ultraconserved elements and their flanking DNA are a rich source of phylogenetic information with strong potential for application across Amniotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Ultraconserved elements are novel phylogenomic markers that resolve placental mammal phylogeny when combined with species-tree analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Ultraconserved elements anchor thousands of genetic markers spanning multiple evolutionary timescales.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232343", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Target capture and massively parallel sequencing of ultraconserved elements for comparative studies at shallow evolutionary time scales.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24021724", "endSection": "title" }, { "offsetInBeginSection": 241, "offsetInEndSection": 380, "text": "Here, we outline a phylogenomic approach using a novel class of phylogenetic markers derived from ultraconserved elements and flanking DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 392, "text": "We applied a new phylogenomic approach to resolve relationships in Neoaves using target enrichment (sequence capture) and high-throughput sequencing of ultraconserved elements (UCEs) in avian genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382987", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 936, "text": "We perform an in silico experiment to demonstrate that sequence flanking 2030 UCEs contains information sufficient to enable unambiguous recovery of the established primate phylogeny.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232343", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1450, "text": "Because many organismal lineages have UCEs, this type of genetic marker and the analytical framework we outline can be applied across the tree of life, potentially reshaping our understanding of phylogeny at many taxonomic levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232343", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 379, "text": "Here, we outline a phylogenomic approach using a novel class of phylogenetic markers derived from ultraconserved elements and flanking DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22207614", "endSection": "abstract" } ] }, { "body": "Treprostinil is an analogue for which prostaglandin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11897647", "http://www.ncbi.nlm.nih.gov/pubmed/22480736", "http://www.ncbi.nlm.nih.gov/pubmed/22918043", "http://www.ncbi.nlm.nih.gov/pubmed/12082102", "http://www.ncbi.nlm.nih.gov/pubmed/23328389", "http://www.ncbi.nlm.nih.gov/pubmed/23597147", "http://www.ncbi.nlm.nih.gov/pubmed/17261956", "http://www.ncbi.nlm.nih.gov/pubmed/22814427", "http://www.ncbi.nlm.nih.gov/pubmed/23231023", "http://www.ncbi.nlm.nih.gov/pubmed/21278326", "http://www.ncbi.nlm.nih.gov/pubmed/20195728", "http://www.ncbi.nlm.nih.gov/pubmed/23429588", "http://www.ncbi.nlm.nih.gov/pubmed/21085923", "http://www.ncbi.nlm.nih.gov/pubmed/12437507", "http://www.ncbi.nlm.nih.gov/pubmed/23307827", "http://www.ncbi.nlm.nih.gov/pubmed/24402297", "http://www.ncbi.nlm.nih.gov/pubmed/20045181", "http://www.ncbi.nlm.nih.gov/pubmed/21400214", "http://www.ncbi.nlm.nih.gov/pubmed/12689580", "http://www.ncbi.nlm.nih.gov/pubmed/23927483", "http://www.ncbi.nlm.nih.gov/pubmed/24033615", "http://www.ncbi.nlm.nih.gov/pubmed/22231731", "http://www.ncbi.nlm.nih.gov/pubmed/18378784", "http://www.ncbi.nlm.nih.gov/pubmed/15920997", "http://www.ncbi.nlm.nih.gov/pubmed/23872196", "http://www.ncbi.nlm.nih.gov/pubmed/21185823", "http://www.ncbi.nlm.nih.gov/pubmed/15302727", "http://www.ncbi.nlm.nih.gov/pubmed/16253609", "http://www.ncbi.nlm.nih.gov/pubmed/17578162" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2784623", "o": "C427248" } ], "ideal_answer": [ "Treprostinil is a prostaglandin I(2) (PGI(2)) analog." ], "exact_answer": [ "Prostaglandin I(2)" ], "concepts": [ "http://www.biosemantics.org/jochem#4270950", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011453", "http://www.biosemantics.org/jochem#4276246", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4270950" ], "type": "factoid", "id": "56c86aa95795f9a73e000018", "snippets": [ { "offsetInBeginSection": 464, "offsetInEndSection": 643, "text": "We investigated the effects of 3 conventional (iloprost, beraprost, and treprostinil) and 1 new (ONO-1301) PGI2 analogs, on the expression of MIP-1\u03b1 expression in human monocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24402297", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1099, "text": "PGI(2) analogues (iloprost, treprostinil and beraprost) significantly increased IL-17A and IL-22 in vitro while decreasing IFN\u03b3 production both in SSc and HD PBMC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22814427", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 482, "text": "The effects of PGI(2) analogs iloprost and treprostinil on cytokine production, maturation and T-cell stimulatory function of human mDCs were investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22231731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Treprostinil, a stable prostacyclin analogue used in the treatment of pulmonary arterial hypertension, is in development as a sustained release oral tablet, treprostinil diolamine (United Therapeutics Corp, Research Triangle Park, NC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429588", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 335, "text": "Treprostinil diolamine is an oral prostacyclin analogue; sustained release tablets of oral treprostinil are currently being evaluated for efficacy and safety as a potential therapy in patients with PAH", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Treprostinil diolamine (oral treprostinil) is a prostacyclin analogue under evaluation for the treatment for pulmonary arterial hypertension (PAH)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24033615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Treprostinil diolamine (oral treprostinil) is a prostacyclin analogue currently being evaluated for the treatment of pulmonary arterial hypertension as a sustained-release (SR) oral tablet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23927483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Treprostinil diethanolamine is an innovative salt form of the prostacyclin analogue, treprostinil sodium, developed as an oral sustained release (SR) osmotic tablet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597147", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 663, "text": "Epoprostenol, a synthetic analogue of prostacyclin, and the chemically stable analogues iloprost, beraprost and treprostinil were tested in randomised controlled trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18378784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Treprostinil is a synthetic prostacyclin analogue with antiplatelet and vasodilatory properties", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23231023", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 555, "text": "Treprostinil is a stable analogue of prostacyclin, which can be administered subcutaneously, intravenously or by inhalation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578162", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 767, "text": "We recently showed that the stable prostacyclin analogue treprostinil, a clinically approved drug for pulmonary arterial hypertension (PAH), significantly reduced the recruitment of fibrocytes to sites of vascular remodeling in experimental hypoxic pulmonary hypertension. Here we report on the molecular mechanism underlying the inhibitory action of treprostinil on the adhesion and differentiation of human fibrocytes. Human fibrocytes expressed the prostanoid receptors, prostaglandin I (IP) receptors and prostaglandin E subtype receptors (EP2 and EP4). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21278326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15302727", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11897647", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The prostacyclin analogue treprostinil blocks NFkappaB nuclear translocation in human alveolar macrophages.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12082102", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The prostacyclin analogues, iloprost and treprostinil are extensively used in treating pulmonary hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480736", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 677, "text": "Iloprost (ILO) and treprostinil (TRP), two prostaglandin I2 analogues, were conjugated to fluorescein-labeled BSA (FLUO-BSA) and compared for IP1 receptor binding/uptake in different lung cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20045181", "endSection": "abstract" } ] }, { "body": "Which are the characteristics of the Meier-Gorlin syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23144622", "http://www.ncbi.nlm.nih.gov/pubmed/21358631", "http://www.ncbi.nlm.nih.gov/pubmed/14564153", "http://www.ncbi.nlm.nih.gov/pubmed/21358632", "http://www.ncbi.nlm.nih.gov/pubmed/23023959", "http://www.ncbi.nlm.nih.gov/pubmed/7981855", "http://www.ncbi.nlm.nih.gov/pubmed/11477602", "http://www.ncbi.nlm.nih.gov/pubmed/11807867", "http://www.ncbi.nlm.nih.gov/pubmed/10213048", "http://www.ncbi.nlm.nih.gov/pubmed/25059018" ], "ideal_answer": [ "The Meier-Gorlin syndrome is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia or hypoplasia of the patellae, and severe pre- and postnatal growth retardation.", "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation ", "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation" ], "type": "summary", "id": "5537766dbc4f83e82800000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23023959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14564153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "The Meier-Gorlin syndrome or ear, patella, short stature syndrome (MIM 224690) is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia/hypoplasia of the patellae, and severe pre- and postnatal growth retardation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11477602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears?\u207b?.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "The Meier-Gorlin syndrome, or ear-patella-short stature syndrome, in sibs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10213048", "endSection": "title" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1211, "text": "Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "The Meier-Gorlin syndrome or ear, patella, short stature syndrome (MIM 224690) is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia/hypoplasia of the patellae, and severe pre- and postnatal growth retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11477602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "We report on an Italian boy with the Meier-Gorlin syndrome (ear-patella-short stature syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11807867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Meier-Gorlin syndrome (ear-patella-short stature syndrome) in an Italian patient: clinical evaluation and analysis of possible candidate genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11807867", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The Meier-Gorlin syndrome (MGS) or ear, patella, short stature syndrome (MIM #224690) is a rare disorder with bilateral microtia, aplasia or hypoplasia of the patellae and severe intra-uterine and post-natal growth retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25059018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Further delineation of the ear, patella, short stature syndrome (Meier-Gorlin syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7981855", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 507, "text": "This combination of anomalies has many similarities to the six cases previously described with the Ear, Patellae, Short stature syndrome (Meier-Gorlin syndrome), which is distinguished by the triad of microtia, absent patellae and growth retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7981855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears\ufffd{\ufffd.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Meier-Gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358631", "endSection": "abstract" }, { "offsetInBeginSection": 1688, "offsetInEndSection": 1933, "text": "While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144622", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1216, "text": "Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144622", "endSection": "abstract" } ] }, { "body": "Which enzyme is deficient in Gaucher's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21982627", "http://www.ncbi.nlm.nih.gov/pubmed/20946052", "http://www.ncbi.nlm.nih.gov/pubmed/17644022", "http://www.ncbi.nlm.nih.gov/pubmed/18627336", "http://www.ncbi.nlm.nih.gov/pubmed/20945983", "http://www.ncbi.nlm.nih.gov/pubmed/22843412", "http://www.ncbi.nlm.nih.gov/pubmed/25429104", "http://www.ncbi.nlm.nih.gov/pubmed/8294487", "http://www.ncbi.nlm.nih.gov/pubmed/15024629", "http://www.ncbi.nlm.nih.gov/pubmed/20074983", "http://www.ncbi.nlm.nih.gov/pubmed/17433057", "http://www.ncbi.nlm.nih.gov/pubmed/15453048", "http://www.ncbi.nlm.nih.gov/pubmed/21653695", "http://www.ncbi.nlm.nih.gov/pubmed/8437594", "http://www.ncbi.nlm.nih.gov/pubmed/20947659", "http://www.ncbi.nlm.nih.gov/pubmed/16781064", "http://www.ncbi.nlm.nih.gov/pubmed/12412377", "http://www.ncbi.nlm.nih.gov/pubmed/18228687", "http://www.ncbi.nlm.nih.gov/pubmed/1379912", "http://www.ncbi.nlm.nih.gov/pubmed/10155294", "http://www.ncbi.nlm.nih.gov/pubmed/22652185", "http://www.ncbi.nlm.nih.gov/pubmed/24485911", "http://www.ncbi.nlm.nih.gov/pubmed/2023606", "http://www.ncbi.nlm.nih.gov/pubmed/24389070" ], "ideal_answer": [ "Gaucher's disease is caused by deficient lysosomal glucocerebrosidase activity", "Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia." ], "exact_answer": [ "Beta glucocerebrosidase" ], "type": "factoid", "id": "571f5e740fd6f91b6800000b", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 90, "text": "Gaucher's disease is caused by deficient lysosomal glucocerebrosidase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18627336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Gaucher's disease is due to glucocerebrosidase deficiency which is responsible for the accumulation of non degraded glucosylceramide within the lysosomes of macrophages: these \"Gaucher cells\", overloaded and alternatively activated, release in patient's plasma numerous compounds (cytokines, chemokines, hydrolases...) some of which contribute to the various tissue damages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18228687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Gaucher's disease is an uncommon inborn recessive autosomal disease, due to a deficient activity of the lysosomal enzyme beta glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15453048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12412377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher's disease, in whom functional glucocerebrosidase is deficient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10155294", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 798, "text": "The common mutations found in the lysosomal enzyme deficient in Gaucher disease, beta-glucocerebrosidase, earmark these proteins for destruction by the endoplasmic reticulum-localised protein folding machinery, resulting in enzyme insufficiency, lysosomal glycolipid storage and subsequent pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22843412", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 309, "text": "It is an essential activator for glucocerebrosidase, the enzyme deficient in Gaucher disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22652185", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 529, "text": "GBA encodes for glucocerebrosidase (GCase), the enzyme deficient in the lysosomal storage disorder, Gaucher disease (GD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21653695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "The gene for glucocerebrosidase ( GBA), the enzyme deficient in Gaucher disease, is located in a gene-rich region on 1q21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15024629", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 777, "text": "\u03b2-glucocerebrosidase, the enzyme deficient in Gaucher disease, also has an essential role in maintaining epidermal permeability function, by regulating the ratio of ceramides to glucosylceramides in the stratum corneum of the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21982627", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 897, "text": "Recently, it was recognized that mutations in the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are associated with an increased incidence of parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20945983", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 594, "text": "Mutations in glucocerebrosidase (GBA), the enzyme deficient in Gaucher disease, are also identified at an increased frequency among Parkinson probands, including those of Ashkenazi Jewish ancestry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16781064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Structure/function relationships of acid beta-glucosidase, the enzyme deficient in Gaucher disease, were evaluated by characterizing the proteins expressed from cDNAs encoding normal and mutant enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8294487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Gaucher disease is an autosomal recessive disorder resulting from deficient activity of the lysosomal enzyme glucocerebrosidase (GBA, E.C.3.2.1.45)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20946052", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 409, "text": "GBA encodes for glucocerebrosidase (GCase), the enzyme deficient in the lysosomal storage disorder, Gaucher disease (GD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21653695", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 472, "text": "LIMP-2 is required for the normal biogenesis and maintenance of lysosomes and endosomes and has been identified as the specific receptor for glucocerebrosidase, the enzyme deficient in Gaucher disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24389070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Mutations in glucocerebrosidase (GCase), the enzyme deficient in Gaucher disease, are a common genetic risk factor for the development of Parkinson disease and related disorders, implicating the role of this lysosomal hydrolase in the disease etiology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25429104", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 307, "text": "This gene is involved in lysosomal mannose-6-phosphate-independent trafficking of \u03b2-glucocerebrosidase (GC), an enzyme deficient in Gaucher disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24485911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Gaucher disease (GD) is a lysosomal storage disorder, caused by deficient activity of the enzyme glucocerebrosidase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22843412", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 498, "text": "The common mutations found in the lysosomal enzyme deficient in Gaucher disease, beta-glucocerebrosidase, earmark these proteins for destruction by the endoplasmic reticulum-localised protein folding machinery, resulting in enzyme insufficiency, lysosomal glycolipid storage and subsequent pathology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2023606", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by a deficiency of glucocerebrosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17433057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Gaucher's disease, the most prevalent of the sphingolipid storage disorders, is caused by a deficiency of the enzyme glucocerebrosidase (glucosylceramidase).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2023606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Pathogenic variants in the glucocerebrosidase gene (GBA) encoding the enzyme deficient in Gaucher's disease (GD) are associated with Parkinson's disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20947659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Gaucher's disease is an uncommon inborn recessive autosomal disease, due to a deficient activity of the lysosomal enzyme beta glucocerebrosidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15453048", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 717, "text": "Recently, it was recognized that mutations in the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are associated with an increased incidence of parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20945983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Gaucher's disease is caused by deficient lysosomal glucocerebrosidase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18627336", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 356, "text": "Functional glucocerebrosidase is deficient in Gaucher's disease, an autosomal recessive lipid storage disorder that affects people of all ethnic backgrounds, but has a higher incidence among East European Jews (Ashkenazim).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1379912", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 658, "text": "We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8437594", "endSection": "abstract" } ] }, { "body": "What is the role of Hsp90 inhibition in cancer therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22134243", "http://www.ncbi.nlm.nih.gov/pubmed/20828379", "http://www.ncbi.nlm.nih.gov/pubmed/23394616", "http://www.ncbi.nlm.nih.gov/pubmed/21964864", "http://www.ncbi.nlm.nih.gov/pubmed/17525527" ], "ideal_answer": [ "Hsp90 inhibition is followed by G1/S cell cycle arrest, downregulation of key signalling proteins such as IGF-IR, Akt, IKK-\u03b1, IKK-\u03b2, FOXO1, ERK1/2 and c-Met, and sequestration-mediated inactivation of NF-\u03baB, resulting in disruption of oncogenic signalling integrity, reduced cell proliferation, decline of cell motility, enhanced apoptotic cell death, and finally, sensitization of cancer cells to additional chemotherapy and/or radiotherapy." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030336", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033673", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051879", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018841", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030308", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045926", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008285", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043407", "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "summary", "id": "531881acb166e2b806000017", "snippets": [ { "offsetInBeginSection": 24, "offsetInEndSection": 259, "text": "Geldanamycin (GA) can be considered a relatively new component with a promising mode of action against human malignancies. It specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394616", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1748, "text": "In toto, we have evinced the dose-dependent and cell line-specific actions of geldanamycin on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of critical Hsp90 clients and subsequent disruption of signaling -oncogenic- integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Low-dose Hsp90 inhibitors tumor-selectively sensitize bladder cancer cells to chemoradiotherapy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134243", "endSection": "title" }, { "offsetInBeginSection": 589, "offsetInEndSection": 857, "text": "Hsp90 inhibitors at low concentrations, which did not exert cytocidal effects but inactivated key anti-apoptotic proteins including erbB2, Akt, and NF-\u03baB, efficiently sensitized bladder cancer cells (T24, 5637 and UM-UC-3 cells) to in vitro CRT by enhancing apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134243", "endSection": "abstract" }, { "offsetInBeginSection": 1251, "offsetInEndSection": 1360, "text": "In mice UM-UC-3 tumor xenografts model, Hsp90 inhibitors successfully potentiated anti-tumor activity of CRT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134243", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1332, "text": "The Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), which simultaneously inactivated both Akt and ERK signaling at noncytocidal concentrations, synergistically potentiated the cytotoxicity of CDDP against BCICs by enhancing CDDP-induced apoptosis in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964864", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1276, "text": "We have demonstrated that, upon 17-AAG treatment, bladder cancer cells are arrested in the G1 phase of the cell cycle and eventually undergo apoptotic cell death in a dose-dependent manner. Furthermore, 17-AAG administration was shown to induce a pronounced downregulation of multiple Hsp90 protein clients and other downstream effectors, such as IGF-IR, Akt, IKK-\u03b1, IKK-\u03b2, FOXO1, ERK1/2 and c-Met, resulting in sequestration-mediated inactivation of NF-\u03baB, reduced cell proliferation and decline of cell motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20828379", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1558, "text": "In total, we have clearly evinced a dose-dependent and cell type-specific effect of 17-AAG on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of multiple Hsp90 clients and subsequent disruption of signaling integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20828379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525527", "endSection": "title" }, { "offsetInBeginSection": 717, "offsetInEndSection": 808, "text": "GA downregulated Met by inhibiting new protein maturation, thereby dampening HGF signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525527", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 1189, "text": "HGF and chemical hypoxia with CoCl2 cooperatively promoted in vitro invasion and vascular endothelial growth factor (VEGF) secretion, while CoCl2 but not HGF activated urokinase-type plasminogen activator and matrix metalloproteinase 2, both of which promote invasion and angiogenesis. Low dose GA (100 nmol/L) inhibited these processes by suppressing both HGF and HIF-1 pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525527", "endSection": "abstract" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1326, "text": "Notably, brief GA pretreatment inhibited in vitro invasion and VEGF secretion induced by HGF as effectively as did continuous treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525527", "endSection": "abstract" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1514, "text": "Moreover, we found that GA inhibited activation of focal adhesion kinase, focal adhesion assembly, and actin reorganization induced by HGF and integrin engagement by extracellular matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525527", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1752, "text": "GA widely suppresses extrinsic stimuli-induced signaling that contribute to tumor invasion and angiogenesis in this bladder carcinoma model, suggesting the utility of Hsp90 inhibitors in preventing tumor progression and metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525527", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1066, "text": "upon geldanamycin treatment, bladder cancer cells are prominently arrested in the G1 phase of cell cycle and eventually undergo programmed cell death via combined activation of apoptosis and autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394616", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1453, "text": "geldanamycin administration proved to induce prominent downregulation of several Hsp90 protein clients and downstream effectors, such as membrane receptors (IGF-IR and c-Met), protein kinases (Akt, IKK\u03b1, IKK\u03b2 and Erk1/2) and transcription factors (FOXOs and NF-\u03ba\u0392), therefore resulting in the impairment of proliferative -oncogenic- signaling and reduction of cell motility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394616", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 318, "text": "17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin antibiotic, specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in cellular signalin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20828379", "endSection": "abstract" } ] }, { "body": "Which is the most common type of pediatric cerebellar tumor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21315459", "http://www.ncbi.nlm.nih.gov/pubmed/23951168", "http://www.ncbi.nlm.nih.gov/pubmed/25499213", "http://www.ncbi.nlm.nih.gov/pubmed/6502196", "http://www.ncbi.nlm.nih.gov/pubmed/21681603", "http://www.ncbi.nlm.nih.gov/pubmed/16479172", "http://www.ncbi.nlm.nih.gov/pubmed/9447621" ], "ideal_answer": [ "Medulloblastoma is the most common malignant cerebellar tumor seen in the pediatric age group, which has a known ability to metastasize extraneurally.", "Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally " ], "exact_answer": [ "Medulloblastoma" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:5059", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002528" ], "type": "factoid", "id": "55376f19bc4f83e82800000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21681603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6502196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Medulloblastoma (MB) is the most common malignant pediatric brain tumor which is thought to originate from cerebellar granule cell precursors (CGNPs) that fail to properly exit the cell cycle and differentiate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16479172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21681603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Medulloblastoma, the most common pediatric brain tumor, is thought to arise from deregulated proliferation of cerebellar granule precursor (CGP) cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23951168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Medulloblastoma (MB) is the most common malignant pediatric brain tumor and is thought to arise from genetic anomalies in developmental pathways required for the normal maturation of the cerebellar cortex, notably developmental pathways for granule cell progenitor (GCP) neurogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21315459", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 624, "text": "Most adult brain tumors are supratentorial malignant gliomas, whereas the most common malignant pediatric brain tumor is the cerebellar primitive neuroectodermal tumor (medulloblastoma).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9447621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Mouse models have increased our understanding of the pathogenesis of medulloblastoma (MB), the most common malignant pediatric brain tumor that often forms in the cerebellum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25499213", "endSection": "abstract" } ] }, { "body": "Which is the E3 ubiquitin ligase of Hsp90?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23344957", "http://www.ncbi.nlm.nih.gov/pubmed/17209571", "http://www.ncbi.nlm.nih.gov/pubmed/20618441", "http://www.ncbi.nlm.nih.gov/pubmed/23429937" ], "ideal_answer": [ "Carboxyl terminus of hsc70-interacting protein (CHIP) can mediate ubiquitination of the 90 kDa heat-shock protein (hsp90) in vitro, with subsequent proteasomal degradation of the chaperone." ], "exact_answer": [ "Carboxyl terminus of hsc70-interacting protein (CHIP)" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000151", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051879", "http://www.uniprot.org/uniprot/UB2E3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004842", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018841", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044767", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043743" ], "type": "factoid", "id": "5319a7d2b166e2b806000029", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 232, "text": "C-terminal Hsp-interacting protein (CHIP) is an HSP70 and HSP90 interacting co-chaperone and an E3 ubiquitin ligase. Previous studies have reported the role of CHIP in cancer progression by targeting protein degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The U-box E3 ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein) binds Hsp90 and/or Hsp70 via its tetratricopeptide repeat (TPR), facilitating ubiquitination of the chaperone-bound client proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23344957", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1055, "text": "In vitro ubiquitination assays indicated that Ca(2+)/S100A2 and S100P are efficient and specific inhibitors of CHIP-mediated ubiquitination of Hsp70, Hsp90, HSF1, and Smad1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23344957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "The E3 ubiquitin ligase CHIP (C-terminus of Hsc70-interacting protein) is believed to be a central player in the cellular triage decision, as it links the molecular chaperones Hsp70/Hsc70 and Hsp90 to the ubiquitin proteasomal degradation pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20618441", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 675, "text": "We found that CHIP has a sixfold higher affinity for Hsp90 compared with Hsc70.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20618441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Carboxyl terminus of hsc70-interacting protein (CHIP) can remodel mature aryl hydrocarbon receptor (AhR) complexes and mediate ubiquitination of both the AhR and the 90 kDa heat-shock protein (hsp90) in vitro", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209571", "endSection": "title" }, { "offsetInBeginSection": 619, "offsetInEndSection": 864, "text": "The analysis of the sucrose-gradient-fractionated in vitro translated AhR complexes revealed that CHIP can mediate hsp90 ubiquitination while cooperating with unidentified factors to promote the ubiquitination of mature unliganded AhR complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209571", "endSection": "abstract" } ] }, { "body": "Which are the major phycobiliproteins present in cyanobacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15242812", "http://www.ncbi.nlm.nih.gov/pubmed/18062815", "http://www.ncbi.nlm.nih.gov/pubmed/16569506", "http://www.ncbi.nlm.nih.gov/pubmed/2431391", "http://www.ncbi.nlm.nih.gov/pubmed/1409666", "http://www.ncbi.nlm.nih.gov/pubmed/24063013", "http://www.ncbi.nlm.nih.gov/pubmed/20306699", "http://www.ncbi.nlm.nih.gov/pubmed/12416885", "http://www.ncbi.nlm.nih.gov/pubmed/17234404", "http://www.ncbi.nlm.nih.gov/pubmed/10744320", "http://www.ncbi.nlm.nih.gov/pubmed/6802826", "http://www.ncbi.nlm.nih.gov/pubmed/16592117", "http://www.ncbi.nlm.nih.gov/pubmed/3127591", "http://www.ncbi.nlm.nih.gov/pubmed/18954974", "http://www.ncbi.nlm.nih.gov/pubmed/1903389", "http://www.ncbi.nlm.nih.gov/pubmed/9548282", "http://www.ncbi.nlm.nih.gov/pubmed/11690696", "http://www.ncbi.nlm.nih.gov/pubmed/19224391", "http://www.ncbi.nlm.nih.gov/pubmed/8187585", "http://www.ncbi.nlm.nih.gov/pubmed/16190625", "http://www.ncbi.nlm.nih.gov/pubmed/12767340", "http://www.ncbi.nlm.nih.gov/pubmed/8344905", "http://www.ncbi.nlm.nih.gov/pubmed/23664178", "http://www.ncbi.nlm.nih.gov/pubmed/3931221", "http://www.ncbi.nlm.nih.gov/pubmed/2502578", "http://www.ncbi.nlm.nih.gov/pubmed/24435274", "http://www.ncbi.nlm.nih.gov/pubmed/16593484", "http://www.ncbi.nlm.nih.gov/pubmed/3086870", "http://www.ncbi.nlm.nih.gov/pubmed/7678762", "http://www.ncbi.nlm.nih.gov/pubmed/11504069", "http://www.ncbi.nlm.nih.gov/pubmed/8419325" ], "ideal_answer": [ "Phycobiliproteins are derived from the photosynthetic apparatus of cyanobacteria and eukaryotic algae, and form their large extrinsic antenna complexes called phycobilisomes. Phycobilisomes have a core composed from allophycocyanin (APC) and rods, which are of variable phycobiliprotein composition. C-Phycocyanin (C-Pc) is one of the major light harvesting biliprotein pigments constitutively produced by many cyanobacteria, such as Spirulina platenesis (a blue-green alga). B-Phycoerythrin (B-PE) is an other major light-harvesting pigment found in red algae and cyanobacteria. R-phycoerythrin (R-PE) is the major light-harvesting pigment protein of most red algal phycobilisomes." ], "exact_answer": [ [ "allophycocyanin (APC)" ], [ "C-Phycocyanin (C-Pc)" ], [ "B-Phycoerythrin (B-PE)" ], [ "R-phycoerythrin (R-PE)" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000458", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052979" ], "type": "list", "id": "55439140ed966d112c00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "An extensive range of pigments including phycobiliproteins are present in algae. C-phycocyanin (C-PC), a phycobiliprotein, is one of the key pigments of Spirulina", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24063013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Spirulina platensis produces nutraceutical product C-phycocyanin (C-PC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23664178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "C-Phycocyanin (C-Pc) is one of the major biliprotein pigments of unicellular cyanbacterium of Spirulina platenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20306699", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 258, "text": "Marine Synechococcus owe their specific vivid color (ranging from blue-green to orange) to their large extrinsic antenna complexes called phycobilisomes, comprising a central allophycocyanin core and rods of variable phycobiliprotein composition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18062815", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 408, "text": "Three major pigment types can be defined depending on the major phycobiliprotein found in the rods (phycocyanin, phycoerythrin I or phycoerythrin II)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18062815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Phycocyanin--a major phycobiliprotein constitutively produced by many cyanobacteria--", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17234404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "R-phycoerythrin was isolated and purified from a red alga, Polysiphonia urceolata Grev", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16569506", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 180, "text": "C-phycocyanin (C-PC), one of the major phycobiliproteins of Spirulina platensis (a blue-green alga)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16190625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "C-Phycocyanin (C-PC), the major light harvesting biliprotein from Spirulina platensis is of greater importance because of its various biological and pharmacological properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15242812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "B-Phycoerythrin (B-PE) is a major light-harvesting pigment of microalgae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12767340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Phycoerythrin is a major light-harvesting pigment of red algae and cyanobacteria that is widely used as a fluorescent probe and analytical reagent. In this paper, B-phycoerythrin and R-phycocyanin in native state, from the red alga Porphyridium cruentum were obtained by an inexpensive and simple process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11690696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Phycobiliproteins are derived from the photosynthetic apparatus of cyanobacteria and eukaryotic algae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11504069", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 667, "text": "the three major phycobiliprotein types, namely allophycocyanin, phycocyanin, and phycoerythrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11504069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Phycoerythrin is a major light-harvesting pigment of red algae and cyanobacteria widely used as a fluorescent probe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10744320", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 271, "text": "allophycocyanin (APC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8187585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "R-phycoerythrin is the major light-harvesting pigment protein of most red algal phycobilisomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8344905", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1172, "text": "The purified protein had three absorption peaks at 498, 535, and 565 nm and displayed a fluorescence maximum at 580 nm, which was consistent with the typical spectrum of R-phycoerythrin. The purified R-PE was also identified with electrophoresis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16569506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Phycobilisomes, the major light-harvesting complexes of cyanobacteria are multimolecular structures made up of chromophoric proteins called phycobiliproteins and non chromophoric linker polypeptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2431391", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 397, "text": "We report here the isolation and nucleotide sequence of the genes, cpeA and cpeB, which in Calothrix PCC 7601 encode the alpha and beta subunits of phycoerythrin, one of the major phycobiliproteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2431391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "The major light-harvesting complex in eukaryotic red algae and prokaryotic cyanobacteria is the phycobilisome, a water-soluble complex located on the outer surface of the photosynthetic membranes and composed of both pigmented phycobiliproteins (85%) and non-pigmented linker (15%) polypeptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3127591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Phycocyanin is a major protein produced by cyanobacteria, but very few phycocyanin-producing strains have been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18954974", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 340, "text": "In the present work, phycocyanin (PC) and phycoerythrin (PE) from a Nostoc species are proposed as protein markers for electrophoretic techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9548282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Rod structure of a phycoerythrin II-containing phycobilisome. I. Organization and sequence of the gene cluster encoding the major phycobiliprotein rod components in the genome of marine Synechococcus sp. WH8020.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8419325", "endSection": "title" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1410, "text": "We now present data showing that the allophycocyanin genes and a second set of phycocyanin genes are transcribed into major mRNAs of 1400 and 1600 bases, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3086870", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 847, "text": "The amino acid sequences deduced from both rpeA and rpeB present strong homologies with those previously reported for phycoerythrin subunits of cyanobacteria, rhodophyta, and cryptomonads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1409666", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1605, "text": "These transcripts are present in RNA isolated from cultures grown in red and green light, although lower levels of the 1600-base phycocyanin transcript are present in cells grown in green light", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3086870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Phycocyanin is a major protein produced by cyanobacteria, but very few phycocyanin-producing strains have been reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18954974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "The major light-harvesting complex in eukaryotic red algae and prokaryotic cyanobacteria is the phycobilisome, a water-soluble complex located on the outer surface of the photosynthetic membranes and composed of both pigmented phycobiliproteins (85%) and non-pigmented linker (15%) polypeptides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3127591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Phycocyanin--a major phycobiliprotein constitutively produced by many cyanobacteria--holds several promising applications in diagnostics, biomedical research, and therapeutics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17234404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Phycobilisomes, the major light-harvesting complexes of cyanobacteria are multimolecular structures made up of chromophoric proteins called phycobiliproteins and non chromophoric linker polypeptides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2431391", "endSection": "abstract" } ] }, { "body": "Is PLK2 involved in alpha-synuclein phosphorylation in the nervous system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21162130", "http://www.ncbi.nlm.nih.gov/pubmed/21838679", "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "http://www.ncbi.nlm.nih.gov/pubmed/19889641", "http://www.ncbi.nlm.nih.gov/pubmed/24128992", "http://www.ncbi.nlm.nih.gov/pubmed/23794260", "http://www.ncbi.nlm.nih.gov/pubmed/19004816" ], "ideal_answer": [ "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in the central nervous system.", "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system " ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/SYUA_SERCA", "http://www.uniprot.org/uniprot/SYUA_ERYPA", "http://www.uniprot.org/uniprot/SYUA_GORGO", "http://www.uniprot.org/uniprot/SYUA_PANPA", "http://www.uniprot.org/uniprot/SYUA_ATEGE", "http://www.uniprot.org/uniprot/SYUA_RAT", "http://www.uniprot.org/uniprot/SYUA_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844", "http://www.uniprot.org/uniprot/PLK2_PONAB", "http://www.uniprot.org/uniprot/SYUA_HUMAN" ], "type": "yesno", "id": "550c44d1a103b7801600000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "title" }, { "offsetInBeginSection": 293, "offsetInEndSection": 476, "text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 566, "text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 701, "text": "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 857, "text": "specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 975, "text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 969, "text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 475, "text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "title" }, { "offsetInBeginSection": 474, "offsetInEndSection": 564, "text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 646, "text": "Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (\u03b1-syn) phosphorylating polo-like kinase 2 (PLK2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838679", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1002, "text": "Also, due to the dominant mode of \u03b1-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and \u03b1-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838679", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 615, "text": "To better understand the role of PLK2 in \u03b1-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-\u03b1-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24128992", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 998, "text": "This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and \u03b1-synuclein phosphorylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 656, "text": "PLK2-mediated degradation of \u03b1-synuclein requires both phosphorylation at S129 and PLK2/\u03b1-synuclein complex formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1287, "text": "Overexpression of only PLK2 increased phosphorylation of aggregated \u03b1-syn at S129, which likely is due to increased phosphorylation of soluble \u03b1-syn, which then was incorporated into aggregates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21162130", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 477, "text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 567, "text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 602, "text": "Unlike other kinases reported to partially phosphorylate alpha-syn at Ser-129 in vitro, phosphorylation by PLK2 and PLK3 is quantitative (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19889641", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 702, "text": "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 973, "text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 700, "text": "Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 565, "text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 622, "text": "To better understand the role of PLK2 in \u03b1-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-\u03b1-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24128992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of \u03b1-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23794260", "endSection": "abstract" } ] }, { "body": "In which kingdom do microsporidia belong, according to their current classification scheme?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23917025", "http://www.ncbi.nlm.nih.gov/pubmed/25258042", "http://www.ncbi.nlm.nih.gov/pubmed/22651672", "http://www.ncbi.nlm.nih.gov/pubmed/24104931", "http://www.ncbi.nlm.nih.gov/pubmed/20479876", "http://www.ncbi.nlm.nih.gov/pubmed/24558617", "http://www.ncbi.nlm.nih.gov/pubmed/25182222", "http://www.ncbi.nlm.nih.gov/pubmed/17572334", "http://www.ncbi.nlm.nih.gov/pubmed/23087371", "http://www.ncbi.nlm.nih.gov/pubmed/10666703", "http://www.ncbi.nlm.nih.gov/pubmed/17051209", "http://www.ncbi.nlm.nih.gov/pubmed/22503551", "http://www.ncbi.nlm.nih.gov/pubmed/25134955", "http://www.ncbi.nlm.nih.gov/pubmed/18976912", "http://www.ncbi.nlm.nih.gov/pubmed/9809012" ], "ideal_answer": [ "Traditionally, microsporidia were considered as protozoans, but recently they have been reclassified as the earliest-diverging clade of sequenced fungi. Microsporidia are a diverse group of obligate, intracellular, eukaryotic, spore-forming parasites; they are ubiquitous fungi, with genomes that have undergone a strong reduction." ], "exact_answer": [ "Fungi" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002965", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016814", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021861" ], "type": "factoid", "id": "5547a01cf35db75526000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Microsporidia are a diverse group of obligate, intracellular, eukaryotic, spore-forming parasites. Traditionally, these were considered as protozoans but recently have been reclassified as fungi. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24104931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Microsporidia are ubiquitous fungi with genomes that have undergone a strong reduction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23917025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Microsporidia are unicellular fungi that are obligate endoparasites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23087371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Phylogenomics supports microsporidia as the earliest diverging clade of sequenced fungi.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22651672", "endSection": "title" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1063, "text": "A combined analysis of thousands of gene trees supports a topology in which microsporidia is a sister group to all other sequenced fungi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22651672", "endSection": "abstract" }, { "offsetInBeginSection": 1410, "offsetInEndSection": 1533, "text": "Altogether, our data strongly support a scenario in which microsporidia is the earliest-diverging clade of sequenced fungi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22651672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Microsporidia are a large diverse group of intracellular parasites now considered as fungi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503551", "endSection": "abstract" }, { "offsetInBeginSection": 1694, "offsetInEndSection": 1954, "text": "The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479876", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1100, "text": "The kingdom Fungi is expanded by adding Microsporidia, because of protein sequence evidence that these amitochondrial intracellular parasites are related to conventional Fungi, not Protozoa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9809012", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 319, "text": "The preponderance of evidence as to the origin of the microsporidia reveals a close relationship with the fungi, either within the kingdom or as a sister group to it.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479876", "endSection": "abstract" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1508, "text": "In a subsequent analysis, we excluded the other Microsporidia from the analysis to look for relationships before the divergence of Microsporidia, and found that 43% of the microsporidial genes scored highest with fungal genes, and a higher mean LPI was found with Fungi than with other kingdoms, suggesting that Microsporidia is closely related to Fungi at the genomic level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25134955", "endSection": "abstract" }, { "offsetInBeginSection": 1753, "offsetInEndSection": 2038, "text": "CONCLUSION/SIGNIFICANCE: The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479876", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1105, "text": "The kingdom Fungi is expanded by adding Microsporidia, because of protein sequence evidence that these amitochondrial intracellular parasites are related to conventional Fungi, not Protozoa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9809012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Microorganisms of the microsporidia group are obligated intracellular protozoa that belong to the phylum Microspora; currently they are considered to be related or belong to the fungi reign", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558617", "endSection": "abstract" } ] }, { "body": "What is the inheritance pattern of Emery-Dreifuss muscular dystrophy? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9536090", "http://www.ncbi.nlm.nih.gov/pubmed/8445613", "http://www.ncbi.nlm.nih.gov/pubmed/11799477", "http://www.ncbi.nlm.nih.gov/pubmed/11863303", "http://www.ncbi.nlm.nih.gov/pubmed/23349612", "http://www.ncbi.nlm.nih.gov/pubmed/8042665", "http://www.ncbi.nlm.nih.gov/pubmed/3729752", "http://www.ncbi.nlm.nih.gov/pubmed/4022362", "http://www.ncbi.nlm.nih.gov/pubmed/3203701", "http://www.ncbi.nlm.nih.gov/pubmed/3701378", "http://www.ncbi.nlm.nih.gov/pubmed/12424964", "http://www.ncbi.nlm.nih.gov/pubmed/16585054", "http://www.ncbi.nlm.nih.gov/pubmed/11731280", "http://www.ncbi.nlm.nih.gov/pubmed/9781539", "http://www.ncbi.nlm.nih.gov/pubmed/16791377", "http://www.ncbi.nlm.nih.gov/pubmed/10080180", "http://www.ncbi.nlm.nih.gov/pubmed/2163170", "http://www.ncbi.nlm.nih.gov/pubmed/18266676", "http://www.ncbi.nlm.nih.gov/pubmed/2230849", "http://www.ncbi.nlm.nih.gov/pubmed/15967842" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17680512", "o": "Emery-Dreifuss Muscular Dystrophy" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0410189", "o": "http://linkedlifedata.com/resource/umls/label/A17945027" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17945027", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A1644284", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/pubmed/mesh/Muscular+Dystrophy%2C+Emery-Dreifuss", "o": "http://linkedlifedata.com/resource/pubmed/Mesh" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A1644283", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1644288", "o": "Emery-Dreifuss Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1644282", "o": "Emery-Dreifuss Muscular Dystrophy" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1644287", "o": "Emery Dreifuss Syndrome" } ], "ideal_answer": [ "The inheritance pattern of Emery-Dreifuss muscular dystrophy (EDMD) can be X-linked, autosomal dominant or autosomal recessive." ], "exact_answer": [ [ "X-linked" ], [ "autosomal dominant" ], [ "autosomal recessive" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020389", "http://www.disease-ontology.org/api/metadata/DOID:655", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050172", "http://www.disease-ontology.org/api/metadata/DOID:11726" ], "type": "list", "id": "51656c94298dcd4e51000058", "snippets": [ { "offsetInBeginSection": 139, "offsetInEndSection": 471, "text": ". Loss-of-function truncation mutations in EMD, encoding the nuclear membrane protein emerin, cause X-linked Emery-Dreifuss muscular dystrophy (EDMD) characterized by localized contractures and skeletal myopathy in adolescence, sinus node dysfunction (SND) in early adulthood, and atrial fibrillation as a variably associated trait.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18266676", "endSection": "sections.0" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1903, "text": "Mutation of EMD can underlie X-linked familial AF. Lys37del is associated with epithelial cell emerin deficiency, as in EDMD, yet it causes electrical atriomyopathy in the absence of skeletal muscle disease. Targeted genetic testing of EMD should be considered in patients with SND-associated AF and/or family history suggesting X-linked inheritance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18266676", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The Emery-Dreifuss muscular dystrophy is a form of muscular dystrophy that frequently presents early contractures and cardiac conduction defects, caused by emerin deficiency in the inner nuclear membrane of the muscular fibers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16791377", "endSection": "sections.0" }, { "offsetInBeginSection": 407, "offsetInEndSection": 448, "text": "compatible with X-linked inheritance form", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16791377", "endSection": "sections.0" }, { "offsetInBeginSection": 486, "offsetInEndSection": 567, "text": "The first patient was a member of a family with molecularly proven X-linked EDMD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16585054", "endSection": "sections.0" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1279, "text": "As these resemble the cardiac features of patients with the autosomal dominant variant of EDMD, we examined the lamin A/C gene, identifying a de-novo mutation in the propositus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16585054", "endSection": "sections.0" }, { "offsetInBeginSection": 2077, "offsetInEndSection": 2135, "text": "contribute to disease severity in autosomal dominant EDMD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16585054", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 357, "text": "The STA gene encodes emerin and is one of the genes that is affected in Emery-Dreifuss muscular dystrophy (EDMD). Although it has been reported that EDMD caused by the STA gene mutation is associated with X-linked recessive inheritance, the genotype-phenotype correlations, with special reference to cardiac manifestations, are not well defined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15967842", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 661, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is a muscular disorder characterized by 1) early contracture of the elbows. Achilles tendons and post-cervical muscles, 2) slowly progressive muscle wasting and weakness with a humeroperoneal distribution, and 3) life-threatening cardiomyopathy with conduction block. Most of families with EDMD show X-linked recessive inheritance with mutations in the STA gene on chromosome Xq28, which encodes a protein named emerin. A rare autosomal dominant form of EDMD (AD-EDMD) is caused by mutations in lamin A/C gene (LMNA) on chromosome 1q21. Both emerin and lamin A/C are located in the inner surface membrane of the nucleus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12424964", "endSection": "sections.0" }, { "offsetInBeginSection": 451, "offsetInEndSection": 662, "text": "Emery-Dreifuss muscular dystrophy is an X-linked recessive myopathy. The patient had no familial background of the disease. This patient might have a sporadic inheritance pattern with severe cardiac involvement.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11863303", "endSection": "sections.0" }, { "offsetInBeginSection": 1498, "offsetInEndSection": 1551, "text": "autosomal dominant Emery-Dreifuss muscular dystrophy,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11799477", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 643, "text": "Emery-Dreifuss muscular dystrophy is characterized by the clinical triad of early onset contractures of elbows, Achilles tendons and spine, wasting and weakness with a predominantly humero-peroneal distribution and life-threatening cardiac conduction defects and/or cardiomyopathy. Two main types of inheritance have been described: the X-linked form is caused by mutations in the STA gene on locus Xq28 and the gene for the autosomal dominant form (LMNA gene) has been localized on chromosome 1q11-q23. Recently, mutations in this LMNA gene have been also found to be responsible for the less frequent autosomal recessive form of the disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11731280", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10080180", "endSection": "sections.0" }, { "offsetInBeginSection": 221, "offsetInEndSection": 258, "text": "including X-linked Emery-Dreifuss MD,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9781539", "endSection": "sections.0" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1714, "text": "this form is not X-linked Emery-Dreifuss MD. We suggest that these patients represent a severe MD characterized by early onset distal wasting and severe rigidity of the spine, with probable autosomal recessive inheritance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9781539", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been studied both by DNA sequencing and by emerin protein expression. Fourteen had mutations in the X-linked emerin gene, while three showed evidence of autosomal inheritance. Twelve of the 14 emerin mutations caused early termination of translation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9536090", "endSection": "sections.0" }, { "offsetInBeginSection": 75, "offsetInEndSection": 253, "text": "One family presented a rare autosomal dominant variant of Emery-Dreifuss muscular dystrophy, another with X-linked recessive inheritance showed unusual intrafamilial variability.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8042665", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Emery-Dreifuss muscular dystrophy (EMD) is characterised by (1) early contractures of the Achilles tendons, elbows, and postcervical muscles, (2) slowly progressive muscle wasting and weakness with a predominantly humeroperoneal distribution in the early stages, and (3) cardiomyopathy with conduction defects and risk of sudden death. Inheritance is usually X linked recessive but can be autosomal dominant.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8445613", "endSection": "sections.0" }, { "offsetInBeginSection": 438, "offsetInEndSection": 691, "text": "Tendon contractures may be a partial expression of this myopathic disorder, suggesting an autosomal dominant inheritance with variable penetrance. A muscular dystrophy clinically similar to that of the Emery-Dreifuss (EDMD) type can thus occur in women.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2230849", "endSection": "sections.0" }, { "offsetInBeginSection": 334, "offsetInEndSection": 540, "text": "Since the disease was diagnosed in 3 brothers, the X-coupled recessive type of its inheritance is assumed. An opinion is advanced that the described form is a clinical variety of Emery-Dreyfus myodystrophy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2163170", "endSection": "sections.0" }, { "offsetInBeginSection": 48, "offsetInEndSection": 77, "text": "Emery-Dreifuss syndrome (EDS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3203701", "endSection": "sections.0" }, { "offsetInBeginSection": 385, "offsetInEndSection": 583, "text": "the term Emery-Dreifuss muscular dystrophy should be avoided. Instead, each case of EDS should be classified as myopathic or neurogenic with X chromosome recessive or autosomal dominant inheritance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3203701", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "Emery-Dreifuss muscular dystrophy is a syndrome with five salient features: early and unusual contractures; humeroperoneal muscle wasting; the slow progression of weakness, beginning in childhood; cardiac conduction defects; and X-linked inheritance. We present two cases and detail other reports with a similar constellation of findings with apparent autosomal dominant inheritance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3729752", "endSection": "sections.0" }, { "offsetInBeginSection": 420, "offsetInEndSection": 587, "text": "Emery-Dreifuss muscular dystrophy with proximal weakness in both the upper and lower limbs and X-linked scapuloperoneal muscular dystrophy represent the same disorder.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3701378", "endSection": "sections.0" }, { "offsetInBeginSection": 329, "offsetInEndSection": 538, "text": "There is at least one other report of autosomal dominant transmission of this clinical picture, which had previously only been reported as Emery-Dreifuss muscular dystrophy with X-linked recessive inheritance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4022362", "endSection": "sections.0" } ] }, { "body": "What is the mechanism of action of anticoagulant medication Dabigatran?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20589316", "http://www.ncbi.nlm.nih.gov/pubmed/22388002", "http://www.ncbi.nlm.nih.gov/pubmed/22480286", "http://www.ncbi.nlm.nih.gov/pubmed/21666370", "http://www.ncbi.nlm.nih.gov/pubmed/23466964", "http://www.ncbi.nlm.nih.gov/pubmed/23031622", "http://www.ncbi.nlm.nih.gov/pubmed/16637459", "http://www.ncbi.nlm.nih.gov/pubmed/18425569", "http://www.ncbi.nlm.nih.gov/pubmed/20888031", "http://www.ncbi.nlm.nih.gov/pubmed/21988948", "http://www.ncbi.nlm.nih.gov/pubmed/21526168", "http://www.ncbi.nlm.nih.gov/pubmed/19888525" ], "ideal_answer": [ "Dabigatran is orally administered, reverisble direct and competetive inhibitor of both free and bouded thrombin." ], "concepts": [ "http://www.biosemantics.org/jochem#4242811", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504" ], "type": "summary", "id": "51485a4dd24251bc0500002a", "snippets": [ { "offsetInBeginSection": 161, "offsetInEndSection": 313, "text": "Dabigatran etexilate is a novel oral direct thrombin inhibitor, which provides stroke risk reduction for patients with nonvalvular atrial fibrillation. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23031622", "endSection": "sections.0" }, { "offsetInBeginSection": 455, "offsetInEndSection": 584, "text": "Dabigatran is a potent reversible, competitive direct thrombin inhibitor which is available as the prodrug, Dabigatran etexilate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480286", "endSection": "sections.0" }, { "offsetInBeginSection": 423, "offsetInEndSection": 716, "text": "The recently introduced oral direct thrombin antagonist, dabigatran, has been shown in phase III clinical trials to be noninferior in efficacy to warfarin for the prevention of thromboembolic events in patients with atrial fibrillation, as well as in treatment of acute venous thromboembolism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21988948", "endSection": "sections.0" }, { "offsetInBeginSection": 465, "offsetInEndSection": 669, "text": "Dabigatran is an oral, reversible direct thrombin inhibitor approved in Europe and in several other countries for the prevention of venous thromboembolism after elective knee and hip replacement surgery. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21666370", "endSection": "sections.0" }, { "offsetInBeginSection": 886, "offsetInEndSection": 988, "text": "Dabigatran etexilate is a direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20888031", "endSection": "sections.0" }, { "offsetInBeginSection": 249, "offsetInEndSection": 395, "text": "Direct inhibitors of FXa (rivaroxaban), FVIIa (BMS-593214), thrombin (dabigatran, argatroban) and FXIa (BMS-262084) were included for comparison. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20589316", "endSection": "sections.0" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1196, "text": "Two agents, the direct thrombin inhibitor dabigatran and the direct Factor Xa inhibitor rivaroxaban, have recently been approved in the EU and several other countries for the prevention of VTE after total hip or knee replacement surgery. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19888525", "endSection": "sections.0" }, { "offsetInBeginSection": 702, "offsetInEndSection": 776, "text": "The direct thrombin inhibitor dabigatran is farthest along in development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18425569", "endSection": "sections.0" }, { "offsetInBeginSection": 1742, "offsetInEndSection": 1950, "text": "Lastly, inhibitors of thrombin activity are composed of either indirect (UFH, LMWH), or direct thrombin (FIIa) inhibitors including: hirudin, argatroban, melagatran, ximelagatran, dabigatran, and bivalirudin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16637459", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "The effect of the oral direct activated factor X (factor Xa) inhibitor apixaban on tissue factor-induced thrombin generation in human plasma was investigated in vitro using the calibrated automated thrombogram (CAT) method and compared with the oral direct factor Xa inhibitor rivaroxaban and the direct thrombin inhibitor dabigatran.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466964", "endSection": "sections.0" }, { "offsetInBeginSection": 538, "offsetInEndSection": 780, "text": "The DTI dabigatran etexilate was recently shown to provide superior risk reduction to warfarin for stroke and systemic embolism for patients with nonvalvular AF and recently gained US Food and Drug Administration approval for this indication.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22388002", "endSection": "sections.0" } ] }, { "body": "What is the effect of a defective CLN3 gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10332042", "http://www.ncbi.nlm.nih.gov/pubmed/16251196", "http://www.ncbi.nlm.nih.gov/pubmed/17868323", "http://www.ncbi.nlm.nih.gov/pubmed/16423829", "http://www.ncbi.nlm.nih.gov/pubmed/10509355", "http://www.ncbi.nlm.nih.gov/pubmed/16515873", "http://www.ncbi.nlm.nih.gov/pubmed/15471887", "http://www.ncbi.nlm.nih.gov/pubmed/9384607", "http://www.ncbi.nlm.nih.gov/pubmed/10384264" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q61124", "o": "http://linkedlifedata.com/resource/#_5136313132340012" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5136313132340012", "o": "Cln3" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q61124", "o": "http://linkedlifedata.com/resource/#_51363131323400D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51363131323400D", "o": "Battenin" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51363131323400E", "o": "Protein CLN3" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q61124", "o": "http://linkedlifedata.com/resource/#_51363131323400E" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q29611", "o": "http://linkedlifedata.com/resource/#_513239363131008" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513239363131006", "o": "Battenin" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513239363131007", "o": "Protein CLN3" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q29611", "o": "http://linkedlifedata.com/resource/#_513239363131007" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q29611", "o": "http://linkedlifedata.com/resource/#_513239363131006" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513239363131008", "o": "CLN3" } ], "ideal_answer": [ "Mutations in the CLN3 gene, which encodes a lysosomal membrane protein, are responsible for the neurodegenerative disorder juvenile Batten disease." ], "exact_answer": [ "Batten disease", "juvenile-onset neuronal ceroid lipofuscinosis", "JNCL" ], "concepts": [ "http://www.uniprot.org/uniprot/CLN3_MOUSE", "http://www.uniprot.org/uniprot/CLN3_MACFA", "http://www.uniprot.org/uniprot/CLN3_HUMAN", "http://www.uniprot.org/uniprot/CG13_YEAST", "http://www.uniprot.org/uniprot/CLN3_DICDI", "http://www.uniprot.org/uniprot/CLN3_CANFA" ], "type": "factoid", "id": "56b710f276d8bf8d13000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by defective function of the lysosomal membrane glycoprotein CLN3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868323", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 378, "text": "human CLN3 that is defective in Batten disease, localizes to the vacuole", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16423829", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 255, "text": "JNCL results from mutations in CLN3 on chromosome 16p12.1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16515873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Mutations in the CLN3 gene, which encodes a lysosomal membrane protein, are responsible for the neurodegenerative disorder juvenile Batten disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16251196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Batten disease [juvenile-onset neuronal ceroid lipofuscinosis (JNCL)], the most common progressive encephalopathy of childhood, is caused by mutations in a novel lysosomal membrane protein (CLN3) with unknown function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10332042", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 110, "text": "the human CLN3 gene that is defective in Batten disease,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10384264", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 205, "text": "ln3 was recently identified as the gene defective in juvenile Batten disease, an inherited neurodegenerative disease of childhood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10509355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, JNCL), the most common neurodegenerative disorder of childhood, is caused by mutations in a recently identified gene ( CLN3 ) localized to chromosome 16p11.2-12.1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9384607", "endSection": "abstract" } ] }, { "body": "Which genes are regulated by TRalpha2 in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11731613", "http://www.ncbi.nlm.nih.gov/pubmed/18031713", "http://www.ncbi.nlm.nih.gov/pubmed/15831522" ], "ideal_answer": [ "ARB1, ARB2, TAK1, p38, TRalpha1" ], "exact_answer": [ [ "ARB1" ], [ "ARB2" ], [ "TAK1" ], [ "p38" ], [ "TRalpha1" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "list", "id": "517539ca8ed59a060a000027", "snippets": [ { "offsetInBeginSection": 591, "offsetInEndSection": 776, "text": "n FM the reduced mRNA expression of ARB1 (p<0.05, -37%) and ARB2 (p<0.05, -42%) was associated with a reduction of the messenger for TRalpha1 (p<0.05, -85%) and TRalpha2 (p<0.05, -73%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18031713", "endSection": "sections.0" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1052, "text": "hese data reveal that in human heart failure the reduction of beta-adrenergic receptors is associated with reduced expression of both TRalpha1 and TRalpha2 isoforms of thyroid hormone receptors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18031713", "endSection": "sections.0" }, { "offsetInBeginSection": 620, "offsetInEndSection": 793, "text": "Mitigating TRalpha1 effects, both TRalpha2 and TRbeta1 attenuate TRalpha1-induced myocardial growth and gene expression by diminishing TAK1 and p38 activities, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831522", "endSection": "sections.0" }, { "offsetInBeginSection": 422, "offsetInEndSection": 519, "text": "Selective ablation of TRalpha2 resulted in an inevitable, concomitant overexpression of TRalpha1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11731613", "endSection": "sections.0" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1052, "text": "These data reveal that in human heart failure the reduction of beta-adrenergic receptors is associated with reduced expression of both TRalpha1 and TRalpha2 isoforms of thyroid hormone receptors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18031713", "endSection": "sections.0" } ] }, { "body": "Is insulin-like growth factor-I (IGF-I) able to affect tendon protein synthesis in classic Ehlers-Danlos syndrome patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25103963" ], "ideal_answer": [ "Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I ", "In an experimental setting, baseline protein synthesis rates in connective tissue appeared normal in classic Ehlers-Danlos syndrome patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/IGF1_CAPHI", "http://www.disease-ontology.org/api/metadata/DOID:13359", "http://www.uniprot.org/uniprot/IGF_MYXGL" ], "type": "yesno", "id": "54e12ae3ae9738404b000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25103963", "endSection": "title" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1411, "text": "IGF-I injections significantly increased FSR values in cEDS patients but not in controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25103963", "endSection": "abstract" }, { "offsetInBeginSection": 1471, "offsetInEndSection": 1668, "text": "In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25103963", "endSection": "abstract" }, { "offsetInBeginSection": 1477, "offsetInEndSection": 1674, "text": "In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25103963", "endSection": "abstract" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1437, "text": "IGF-I injections significantly increased FSR values in cEDS patients but not in controls (delta values: cEDS 0", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25103963", "endSection": "abstract" } ] }, { "body": "List available methods for transmembrane protein topology prediction.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19470175", "http://www.ncbi.nlm.nih.gov/pubmed/18989393", "http://www.ncbi.nlm.nih.gov/pubmed/19785723", "http://www.ncbi.nlm.nih.gov/pubmed/15111065", "http://www.ncbi.nlm.nih.gov/pubmed/24225132", "http://www.ncbi.nlm.nih.gov/pubmed/16568545", "http://www.ncbi.nlm.nih.gov/pubmed/17237066", "http://www.ncbi.nlm.nih.gov/pubmed/16597327", "http://www.ncbi.nlm.nih.gov/pubmed/19812766", "http://www.ncbi.nlm.nih.gov/pubmed/11590105" ], "ideal_answer": [ "HMMpTM, MetaTM, Philius, HMM_RA, HMMTOP, MEMSAT3, HMM-TM, TMHMM, Phobius and SignalP." ], "exact_answer": [ [ "HMMpTM" ], [ "MetaTM" ], [ "Philius" ], [ "HMM_RA" ], [ "HMMTOP" ], [ "MEMSAT3" ], [ "HMM-TM" ], [ "TMHMM" ], [ "Phobius" ], [ "SignalP" ] ], "type": "list", "id": "554143ad182542114d000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225132", "endSection": "title" }, { "offsetInBeginSection": 716, "offsetInEndSection": 1246, "text": "We report the development of a Hidden Markov Model based method, capable of predicting the topology of transmembrane proteins and the existence of kinase specific phosphorylation and N/O-linked glycosylation sites along the protein sequence. Our method integrates a novel feature in transmembrane protein topology prediction, which results in improved performance for topology prediction and reliable prediction of phosphorylation and glycosylation sites. The method is freely available at http://bioinformatics.biol.uoa.gr/HMMpTM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "MetaTM - a consensus method for transmembrane protein topology prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19785723", "endSection": "title" }, { "offsetInBeginSection": 647, "offsetInEndSection": 1364, "text": "A novel TM consensus method, named MetaTM, is proposed in this work. MetaTM is based on support vector machine models and combines the results of six TM topology predictors and two signal peptide predictors. On a large data set comprising 1460 sequences of TM proteins with known topologies and 2362 globular protein sequences it correctly predicts 86.7% of all topologies. CONCLUSION: Combining several TM predictors in a consensus prediction framework improves overall accuracy compared to any of the individual methods. Our proposed SVM-based system also has higher accuracy than a previous consensus predictor. MetaTM is made available both as downloadable source code and as DAS server at http://MetaTM.sbc.su.se", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19785723", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 1419, "text": "We present a support vector machine-based (SVM) TM protein topology predictor that integrates both signal peptide and re-entrant helix prediction, benchmarked with full cross-validation on a novel data set of 131 sequences with known crystal structures. The method achieves topology prediction accuracy of 89%, while signal peptides and re-entrant helices are predicted with 93% and 44% accuracy respectively. An additional SVM trained to discriminate between globular and TM proteins detected zero false positives, with a low false negative rate of 0.4%. We present the results of applying these tools to a number of complete genomes. Source code, data sets and a web server are freely available from http://bioinf.cs.ucl.ac.uk/psipred/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19470175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 670, "text": "Hidden Markov models (HMMs) have been successfully applied to the tasks of transmembrane protein topology prediction and signal peptide prediction. In this paper we expand upon this work by making use of the more powerful class of dynamic Bayesian networks (DBNs). Our model, Philius, is inspired by a previously published HMM, Phobius, and combines a signal peptide submodel with a transmembrane submodel. We introduce a two-stage DBN decoder that combines the power of posterior decoding with the grammar constraints of Viterbi-style decoding. Philius also provides protein type, segment, and topology confidence metrics to aid in the interpretation of the predictions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989393", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 859, "text": "We report a relative improvement of 13% over Phobius in full-topology prediction accuracy on transmembrane proteins, and a sensitivity and specificity of 0.96 in detecting signal peptides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "HMM_RA: an improved method for alpha-helical transmembrane protein topology prediction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812766", "endSection": "title" }, { "offsetInBeginSection": 241, "offsetInEndSection": 614, "text": "This paper presents a Hidden Markov Model (referred to as HMM_RA) that can predict the topology of alpha-helical transmembrane proteins with improved performance. HMM_RA adopts the same structure as the HMMTOP method, which has five modules: inside loop, inside helix tail, membrane helix, outside helix tail and outside loop. Each module consists of one or multiple states", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812766", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 833, "text": "A new method (MEMSAT3) for predicting transmembrane protein topology from sequence profiles is described and benchmarked with full cross-validation on a standard data set of 184 transmembrane proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17237066", "endSection": "abstract" }, { "offsetInBeginSection": 1698, "offsetInEndSection": 1867, "text": "The algorithms presented here, are easily implemented in any kind of a Hidden Markov Model, whereas the prediction method (HMM-TM) is freely available for academic users", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16597327", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 1056, "text": "TMHMM, the current state-of-the-art method, has less than 52% accuracy in topology prediction on one set of transmembrane proteins of known topology. Based on the observation that there are functional domains that occur preferentially internal or external to the membrane, we have extended the model of TMHMM to incorporate functional domains, using a probabilistic approach originally developed for computational gene finding. Our extension is better than TMHMM in predicting the topology of transmembrane proteins. As prediction of functional domain improves, our system's prediction accuracy will likely improve as well", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16568545", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 1594, "text": "Here, we present Phobius, a combined transmembrane protein topology and signal peptide predictor. The predictor is based on a hidden Markov model (HMM) that models the different sequence regions of a signal peptide and the different regions of a transmembrane protein in a series of interconnected states. Training was done on a newly assembled and curated dataset. Compared to TMHMM and SignalP, errors coming from cross-prediction between transmembrane segments and signal peptides were reduced substantially by Phobius. False classifications of signal peptides were reduced from 26.1% to 3.9% and false classifications of transmembrane helices were reduced from 19.0% to 7.7%. Phobius was applied to the proteomes of Homo sapiens and Escherichia coli. Here we also noted a drastic reduction of false classifications compared to TMHMM/SignalP, suggesting that Phobius is well suited for whole-genome annotation of signal peptides and transmembrane regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15111065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "HMMpTM: improving transmembrane protein topology prediction using phosphorylation and glycosylation site prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225132", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "The HMMTOP transmembrane topology prediction server.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11590105", "endSection": "title" } ] }, { "body": "Does GC content vary markedly within a given isochore?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18092827", "http://www.ncbi.nlm.nih.gov/pubmed/11591467", "http://www.ncbi.nlm.nih.gov/pubmed/22934101", "http://www.ncbi.nlm.nih.gov/pubmed/15978039", "http://www.ncbi.nlm.nih.gov/pubmed/19443854", "http://www.ncbi.nlm.nih.gov/pubmed/17317955", "http://www.ncbi.nlm.nih.gov/pubmed/14962664", "http://www.ncbi.nlm.nih.gov/pubmed/17674077", "http://www.ncbi.nlm.nih.gov/pubmed/21669806", "http://www.ncbi.nlm.nih.gov/pubmed/19108743", "http://www.ncbi.nlm.nih.gov/pubmed/12468094", "http://www.ncbi.nlm.nih.gov/pubmed/16623701", "http://www.ncbi.nlm.nih.gov/pubmed/11319260", "http://www.ncbi.nlm.nih.gov/pubmed/17389148", "http://www.ncbi.nlm.nih.gov/pubmed/17057231", "http://www.ncbi.nlm.nih.gov/pubmed/9254920", "http://www.ncbi.nlm.nih.gov/pubmed/20948965", "http://www.ncbi.nlm.nih.gov/pubmed/21795750" ], "ideal_answer": [ "Isochores are relatively long regions with a relatively homogeneous GC content, and with rather sharp boundaries with neighboring isochores. The base composition, and thus the GC content may differ between different isochores, but is more or less consistent within a given isochore." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001482", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032085" ], "type": "yesno", "id": "55422640ccca0ce74b000004", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 144, "text": "The isochore, a large DNA sequence with relatively small GC variance, is one of the most important structures in eukaryotic genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20948965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Isochores are large regions of relatively homogeneous nucleotide composition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Vertebrate genomes are comprised of isochores that are relatively long (>100 kb) regions with a relatively homogenous (either GC-rich or AT-rich) base composition and with rather sharp boundaries with neighboring isochores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The human genome is composed of large sequence segments with fairly homogeneous GC content, namely isochores", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18092827", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 250, "text": "Isochores, i.e. stretches of DNA with a distinct sequence composition and thus a specific GC content", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17317955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The human genome is composed of long stretches of DNA with distinct GC contents, called isochores or GC-content domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17057231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The human genome is divided into isochores, large stretches (>>300 kb) of genomic DNA with more or less consistent GC content. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11319260", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 290, "text": "Many eukaryotic genomes contain isochore regions, mosaics of homogeneous GC content that can abruptly change from one neighboring isochore to the next.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22934101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "One of the most striking features of mammalian and birds chromosomes is the variation in the guanine-cytosine (GC) content that occurs over scales of hundreds of kilobases to megabases; this is known as the \"isochore\" structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108743", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 709, "text": "The segmentation analysis shows that there are stronger indications of GC content changes at isochore borders than within an isochore.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12468094", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 856, "text": "This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11591467", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 857, "text": "This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11591467", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 983, "text": "An isochore sequence may pass a homogeneity test when GC content fluctuations at smaller length scales are ignored or averaged out.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12468094", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 856, "text": "This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11591467", "endSection": "abstract" } ] }, { "body": "Is tubulin acetylation involved in cell motility?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22193721", "http://www.ncbi.nlm.nih.gov/pubmed/20308065", "http://www.ncbi.nlm.nih.gov/pubmed/20940043", "http://www.ncbi.nlm.nih.gov/pubmed/12024216", "http://www.ncbi.nlm.nih.gov/pubmed/22589388", "http://www.ncbi.nlm.nih.gov/pubmed/23019416", "http://www.ncbi.nlm.nih.gov/pubmed/12677000" ], "ideal_answer": [ "Yes, induction of alpha-tubulin acetylation correlates with inhibition of cell motility, while it is involved in additional cellular processes, e.g. cell cycle progression, differentiation, intracellular trafficking, and signalling. Dynamic microtubule (MT) acetylation/deacetylation mediating cell motility and adhesion is controlled by enzymes such as HDAC6, a major cytoplasmic \u03b1-tubulin deacetylase. While its overexpression and activation is capable to enhance cell motility, HDAC6 activity can also be negatively regulated by a number of cellular inhibitors, thus decreasing the ability of cells for migration." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048870", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054443", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007021", "http://www.uniprot.org/uniprot/TBA_GIBZE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002465", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000145", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014404", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0019799", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050257", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090043", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045298", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000107", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071929" ], "type": "yesno", "id": "5317606eb166e2b80600000d", "snippets": [ { "offsetInBeginSection": 248, "offsetInEndSection": 710, "text": "In this study, we found that paclitaxel induced tubulin acetylation in endothelial and tumor cells, at concentrations that affected cell motility but not proliferation (10(-8) to 10(-9) M, for 4 hours). Induction of tubulin acetylation correlated with inhibition of motility but not proliferation based on a comparison of highly and poorly cytotoxic taxanes (paclitaxel and IDN5390) and tumor cell lines sensitive and resistant to paclitaxel (1A9 and 1A9 PTX22).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23019416", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1226, "text": "we found that overexpression of the tubulin deacetylase SIRT2 increased cell motility and reduced cell response to the anti-motility activity of paclitaxel. Conversely, the SIRT2 inhibitor splitomicin reduced cell motility and potentiated the anti-motility activity of paclitaxel. The inhibitory effect was further potentiated by the addition of the HDAC6 inhibitor trichostatin A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23019416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Cell motility and adhesion involves dynamic microtubule (MT) acetylation/deacetylation, a process regulated by enzymes as HDAC6, a major cytoplasmic \u03b1-tubulin deacetylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22193721", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 709, "text": "GRK2 and HDAC6 colocalize in the lamellipodia of migrating cells, leading to local tubulin deacetylation and enhanced motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22193721", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1014, "text": "This review highlights the emerging roles of tubulin acetylation in multiple cellular functions, ranging from cell motility, cell cycle progression or cell differentiation to intracellular trafficking and signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20940043", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 1017, "text": "Our results indicate that TPPP/p25 binds to HDAC6 (histone deacetylase 6), an enzyme responsible for tubulin deacetylation. Moreover, we demonstrated that the direct interaction of these two proteins resulted in the inhibition of the deacetylase activity of HDAC6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20308065", "endSection": "abstract" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 1745, "text": "Finally, we demonstrated that, similarly to other HDAC6 inhibitors, TPPP/p25 influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility as demonstrated by time lapse video experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20308065", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 462, "text": "\"tubacin,\" which inhibits alpha-tubulin deacetylation in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12677000", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 677, "text": "We provide evidence that class II histone deacetylase 6 (HDAC6) is the intracellular target of tubacin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12677000", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 901, "text": "Tubacin treatment did not affect the stability of microtubules but did decrease cell motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12677000", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1376, "text": "They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12677000", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1164, "text": "Furthermore, overexpression of HDAC6 promotes chemotactic cell movement, supporting the idea that HDAC6-mediated deacetylation regulates microtubule-dependent cell motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12024216", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1334, "text": "HDAC6 is a major cytoplasmic a-tubulin deacetylase that is involved in cell motility and adhesion. GRK2 dynamically and directly associates with and phosphorylates HDAC6 to stimulate its a-tubulin deacetylase activity at specific cellular localizations, such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589388", "endSection": "abstract" } ] }, { "body": "List available genetic multicolor cell labeling techiniques in Drosophila", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25657347", "http://www.ncbi.nlm.nih.gov/pubmed/21297621", "http://www.ncbi.nlm.nih.gov/pubmed/21297619" ], "ideal_answer": [ "Flybow and Drosophila Brainbow." ], "exact_answer": [ [ "Flybow" ], [ "Drosophila Brainbow" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004331", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007553" ], "type": "list", "id": "56b739d976d8bf8d13000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297619", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1080, "text": "To facilitate studies of neural network architecture and formation, we generated three Drosophila melanogaster variants of the mouse Brainbow-2 system, called Flybow. Sequences encoding different membrane-tethered fluorescent proteins were arranged in pairs within cassettes flanked by recombination sites. Flybow combines the Gal4-upstream activating sequence binary system to regulate transgene expression and an inducible modified Flp-FRT system to drive inversions and excisions of cassettes. This provides spatial and temporal control over the stochastic expression of one of two or four reporters within one sample. Using the visual system, the embryonic nervous system and the wing imaginal disc, we show that Flybow in conjunction with specific Gal4 drivers can be used to visualize cell morphology with high resolution. Finally, we demonstrate that this labeling approach is compatible with available Flp-FRT-based techniques, such as mosaic analysis with a repressible cell marker; this could further support the genetic analysis of neural circuit assembly and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Drosophila Brainbow: a recombinase-based fluorescence labeling technique to subdivide neural expression patterns.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297621", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1083, "text": "We developed a multicolor neuron labeling technique in Drosophila melanogaster that combines the power to specifically target different neural populations with the label diversity provided by stochastic color choice. This adaptation of vertebrate Brainbow uses recombination to select one of three epitope-tagged proteins detectable by immunofluorescence. Two copies of this construct yield six bright, separable colors. We used Drosophila Brainbow to study the innervation patterns of multiple antennal lobe projection neuron lineages in the same preparation and to observe the relative trajectories of individual aminergic neurons. Nerve bundles, and even individual neurites hundreds of micrometers long, can be followed with definitive color labeling. We traced motor neurons in the subesophageal ganglion and correlated them to neuromuscular junctions to identify their specific proboscis muscle targets. The ability to independently visualize multiple lineage or neuron projections in the same preparation greatly advances the goal of mapping how neurons connect into circuits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Brainbow: new resources and emerging biological applications for multicolor genetic labeling and analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25657347", "endSection": "title" } ] }, { "body": "Which growth factors are known to be involved in the induction of EMT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23027863", "http://www.ncbi.nlm.nih.gov/pubmed/23437179", "http://www.ncbi.nlm.nih.gov/pubmed/17720949", "http://www.ncbi.nlm.nih.gov/pubmed/22547830", "http://www.ncbi.nlm.nih.gov/pubmed/16365168", "http://www.ncbi.nlm.nih.gov/pubmed/21680037", "http://www.ncbi.nlm.nih.gov/pubmed/15121845", "http://www.ncbi.nlm.nih.gov/pubmed/11790801", "http://www.ncbi.nlm.nih.gov/pubmed/7593195", "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "http://www.ncbi.nlm.nih.gov/pubmed/11526479", "http://www.ncbi.nlm.nih.gov/pubmed/16868306", "http://www.ncbi.nlm.nih.gov/pubmed/18792103", "http://www.ncbi.nlm.nih.gov/pubmed/20531305", "http://www.ncbi.nlm.nih.gov/pubmed/22627188", "http://www.ncbi.nlm.nih.gov/pubmed/23810808", "http://www.ncbi.nlm.nih.gov/pubmed/20075196" ], "ideal_answer": [ "EMT is characterized by acquisition of cell motility, modifications of cell morphology, and cell dissociation correlating with the loss of desmosomes from the cellular cortex. A number of growth factors have been shown to be involved in this process. These include fibroblast growth factors (FGFs), TGF-\u03b21, TGF-\u03b22, TNF-\u03b1, CCN family, Sonic Hedgehog (SHh), Notch1, GF-\u03b2, Wnt, EGF, bFGF, IGF-I and IGF-II." ], "exact_answer": [ [ "fibroblast growth factors (FGFs)" ], [ "TGF-\u03b21" ], [ "TGF-\u03b22" ], [ "TNF-\u03b1" ], [ "CCN family" ], [ "Sonic Hedgehog (SHh)" ], [ "Notch1" ], [ "GF-\u03b2" ], [ "Wnt" ], [ "EGF" ], [ "bFGF" ], [ "IGF-I" ], [ "IGF-II" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070848", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005346", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0019838", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017978", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008083", "http://www.biosemantics.org/jochem#4249315", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058750", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D036341" ], "type": "list", "id": "5319abffb166e2b80600002f", "snippets": [ { "offsetInBeginSection": 475, "offsetInEndSection": 755, "text": "Moreover, recent studies have shown that most EMT cases are regulated by soluble growth factors or cytokines. Among these factors, fibroblast growth factors (FGFs) execute diverse functions by binding to and activating members of the FGF receptor (FGFR) family, including FGFR1-4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 904, "text": "Fibroblast growth factor receptor 1 is an oncoprotein that is involved in tumorigenesis, and PD173074 is known to be a selective inhibitor of FGFR1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "endSection": "abstract" }, { "offsetInBeginSection": 1485, "offsetInEndSection": 1595, "text": "Fibroblast growth factor receptor 1 was also overexpressed in EMT cell lines compared with non-EMT cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "endSection": "abstract" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1734, "text": "Furthermore, treatment of HOC313 cells with PD173074 suppressed cellular proliferation and invasion and reduced ERK1/2 and p38 activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "endSection": "abstract" }, { "offsetInBeginSection": 1846, "offsetInEndSection": 2060, "text": "In addition, the expression levels of certain matrix metalloproteinases (MMPs), whose genes contain activator protein-1 (AP-1) promoter sites, as well as Snail1 and Snail2 were reduced following PD173074 treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "endSection": "abstract" }, { "offsetInBeginSection": 2073, "offsetInEndSection": 2202, "text": "Taken together, these data suggest that PD173074 inhibits the MAPK pathway, which regulates the activity of AP-1 and induces MET.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045665", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 136, "text": "egulation of Na,K-ATPase \u03b21-subunit in TGF-\u03b22-mediated epithelial-to-mesenchymal transition in human retinal pigmented epithelial cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810808", "endSection": "title" }, { "offsetInBeginSection": 421, "offsetInEndSection": 518, "text": "The EMT process is mediated via exposure to vitreous cytokines and growth factors such as TGF-\u03b22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810808", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 747, "text": "Previous studies have shown that Na,K-ATPase is required for maintaining a normal polarized epithelial phenotype and that decreased Na,K-ATPase function and subunit levels are associated with TGF-\u03b21-mediated EMT in kidney cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810808", "endSection": "abstract" }, { "offsetInBeginSection": 1868, "offsetInEndSection": 1954, "text": "loss of Na,K-ATPase \u03b21 is a potential contributor to TGF-\u03b22-mediated EMT in RPE cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810808", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 319, "text": "MT (epithelial-mesenchymal transition) is crucial for cancer cells to acquire invasive phenotypes. In A549 lung adenocarcinoma cells, TGF-\u03b2 elicited EMT in Smad-dependent manner and TNF-\u03b1 accelerated this process, as confirmed by cell morphology, expression of EMT markers, capacity of gelatin lysis and cell invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23437179", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 719, "text": "Comprehensive expression analysis unraveled genes differentially regulated by TGF-\u03b2 and TNF-\u03b1, such as cytokines, chemokines, growth factors and ECM (extracellular matrices), suggesting the drastic change in autocrine/paracrine signals as well as cell-to-ECM interactions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23437179", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 320, "text": "Our recent studies found that CCN1 plays a critical role in pancreatic carcinogenesis through the induction of EMT and stemness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23027863", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 694, "text": "Here we show that CCN1 regulates the Sonic Hedgehog (SHh) signaling pathway, which is associated with the PDAC progression and poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23027863", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 784, "text": "SHh regulation by CCN1 in pancreatic cancer cells is mediated through the active Notch-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23027863", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1580, "text": "These extensive studies propose that targeting CCN1 can provide a new treatment option for patients with pancreatic cancer since blocking CCN1 simultaneously blocks two critical pathways (i.e. SHh and Notch1) associated with the development of the disease as well as drug resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23027863", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 47, "text": "GF-\u03b2-induced epithelial-mesenchymal transition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627188", "endSection": "title" }, { "offsetInBeginSection": 691, "offsetInEndSection": 1133, "text": "The cytokine TGF-\u03b2, which is expressed by tumor-infiltrating immune cells, stands out as a master regulator of the pro-invasive tumor microenvironment. TGF-\u03b2 cooperates with stem cell pathways, such as Wnt and Ras signaling, to induce EMT. In addition, TGF-\u03b2 contributes to an EMT-permissive microenvironment by switching the phenotypes of tumor-infiltrating immune cells, which thereby mount pro-invasive and pro-metastatic immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627188", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1367, "text": "In this review, we discuss the role of TGF-\u03b2-induced EMT as a link between cancer and inflammation in the context of questions, which from our point of view are key to answer in order to understand the functionality of EMT in tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627188", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 157, "text": "ranscription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22547830", "endSection": "title" }, { "offsetInBeginSection": 516, "offsetInEndSection": 693, "text": "Treatment of HT29 and DLD-1 cells with EGF and/or basic FGF (bFGF) induced EMT and significantly increased sLe(x/a) expression resulting in enhanced E-selectin binding activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22547830", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1130, "text": "Upon hypoxia, TGF\u03b2 addition or EGFRvIII expression, MCF7, A549 and NMuMG epithelial cells acquired a spindle shape and lost cell-cell contacts. Expression of epithelial markers such as E-cadherin decreased, whereas mesenchymal markers such as vimentin and N-cadherin increased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680037", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 494, "text": "The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-beta, whose activities are dysregulated during malignant tumor progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20531305", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1524, "text": "Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20075196", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 123, "text": "nflammatory cytokines augments TGF-beta1-induced epithelial-mesenchymal transition in A549 cells by up-regulating TbetaR-I", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18792103", "endSection": "title" }, { "offsetInBeginSection": 226, "offsetInEndSection": 481, "text": "In this study, we report that cytomix (a mixture of IL-1beta, TNF-alpha and IFN-gamma) significantly enhances TGF-beta1-induced EMT in A549 cells as evidenced by acquisition of fibroblast-like cell shape, loss of E-cadherin, and reorganization of F-actin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18792103", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 643, "text": "IL-1beta or TNF-alpha alone can also augment TGF-beta1-induced EMT. However, a combination of IL-1beta and TNF-alpha or the cytomix is more potent to induce EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18792103", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1207, "text": "These results indicate that inflammatory cytokines together with TGF-beta1 may play an important role in the development of fibrosis and tumor progress via the mechanism of epithelial-mesenchymal transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18792103", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1329, "text": "TGF-beta stimulated epithelial to mesenchyme transdifferentiation (EMT) in the presence of TGF-alpha, as characterized by increased expression of fibronectin and changes in TGF-beta receptor binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17720949", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 248, "text": "EMT is typically induced by transforming growth factor-beta1 (TGF-beta1) and inhibited by hepatocyte growth factor (HGF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16868306", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1112, "text": "Exposure of MDCK cells to 10 ng/ml TGF-beta1 for 72 h induced EMT as evidenced by conversion to the spindle-like morphology, loss of E-cadherin, and activation of alpha-smooth muscle actin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16868306", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 856, "text": "In contrast, Akt1 down-regulation in IGF-IR-stimulated cells promoted dramatic neomorphic effects characteristic of an epithelial-mesenchymal transition (EMT) and enhanced cell migration induced by IGF-I or EGF stimulation. The phenotypic effects of Akt1 down-regulation were accompanied by enhanced extracellular signal-related kinase (ERK) activation, which contributed to the induction of migration and EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365168", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 164, "text": "ransforming growth factors beta (TGF-betas) inhibit growth of epithelial cells and induce differentiation changes, such as epithelial-mesenchymal transition (EMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15121845", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 711, "text": "Ha-Ras cooperates with transforming growth factor beta (TGFbeta) to cause epithelial mesenchymal transition (EMT) characterized by spindle-like cell morphology, loss of epithelial markers, and induction of mesenchymal markers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11790801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "IGF-II induces rapid beta-catenin relocation to the nucleus during epithelium to mesenchyme transition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11526479", "endSection": "title" }, { "offsetInBeginSection": 664, "offsetInEndSection": 745, "text": "We can show that (1) IGF-II induces a rapid epithelium to mesenchymal transition;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11526479", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1268, "text": "Based on the given case of IGF-II and E-cadherin/beta-catenin complex, this study reveals the backbone of a cascade connecting growth factor signaling with cell-cell adhesion during EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11526479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The NBT-II rat carcinoma cell line exhibits two mutually exclusive responses to FGF-1 and EGF, entering mitosis at cell confluency while undergoing an epithelium-to-mesenchyme transition (EMT) when cultured at subconfluency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7593195", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 842, "text": "EMT requires continuous TGFbeta receptor (TGFbeta-R) and oncogenic Ras signaling and is stabilized by autocrine TGFbeta production", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11790801", "endSection": "abstract" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1656, "text": "EMT seems to be a close in vitro correlate of metastasis, both requiring synergism between TGFbeta-R and Raf/MAPK signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11790801", "endSection": "abstract" } ] }, { "body": "What is the function of the yeast protein Aft1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8670839", "http://www.ncbi.nlm.nih.gov/pubmed/11877447", "http://www.ncbi.nlm.nih.gov/pubmed/16024809", "http://www.ncbi.nlm.nih.gov/pubmed/7720713", "http://www.ncbi.nlm.nih.gov/pubmed/21542867", "http://www.ncbi.nlm.nih.gov/pubmed/20439772", "http://www.ncbi.nlm.nih.gov/pubmed/14739928", "http://www.ncbi.nlm.nih.gov/pubmed/9200812", "http://www.ncbi.nlm.nih.gov/pubmed/15649888", "http://www.ncbi.nlm.nih.gov/pubmed/17096368", "http://www.ncbi.nlm.nih.gov/pubmed/19469713", "http://www.ncbi.nlm.nih.gov/pubmed/11223939", "http://www.ncbi.nlm.nih.gov/pubmed/22157760", "http://www.ncbi.nlm.nih.gov/pubmed/21361388", "http://www.ncbi.nlm.nih.gov/pubmed/16648636" ], "ideal_answer": [ "The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions. Aft1 interacts with the FOB (ferrioxamine B) transporter Arn3 and may regulate the ubiquitination of Arn3 in the cytosolic compartment. Aft1 has been implicated in numerous cellular processes including cell-cycle progression and chromosome stability. Aft1 has also been shown to affect a diverse range of cellular processes, including the RIM101 pH pathway, cell-wall stability, DNA damage, protein transport, chromosome stability, mitochondrial function, while it was recently shown to interact with the kinetochore protein Iml3 and to promote pericentromeric cohesin." ], "concepts": [ "http://www.uniprot.org/uniprot/AFT1_YEAST" ], "type": "summary", "id": "51600ca2298dcd4e51000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Using a scheme for selecting mutants of Saccharomyces cerevisiae with abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates the control of iron uptake", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7720713", "endSection": "sections.0" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1358, "text": "AFT1 functions to activate transcription of target genes in response to iron deprivation and thereby plays a central role in iron homeostasis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7720713", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8670839", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Iron deprivation of Saccharomyces cerevisiae induces transcription of genes required for high-affinity iron uptake. AFT1 mediates this transcriptional control.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8670839", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9200812", "endSection": "title" }, { "offsetInBeginSection": 1260, "offsetInEndSection": 1461, "text": "Aft1 displays phosphorylation modifications depending on the growth stage of the cells, and it might link induction of genes for iron uptake to other metabolically dominant requirement for cell growth.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9200812", "endSection": "sections.0" }, { "offsetInBeginSection": 352, "offsetInEndSection": 431, "text": "an aft1 mutation in S. cerevisiae that makes cells dependent on iron for growth", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11223939", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11877447", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11877447", "endSection": "sections.0" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1177, "text": "the nuclear export of Aft1 is critical for ensuring iron-responsive transcriptional activation of the Aft1 regulon and that the nuclear import/export systems are involved in iron sensing by Aft1 in S. cerevisiae.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11877447", "endSection": "sections.0" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1197, "text": "the Aft1 iron-responsive DNA-binding factor", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14739928", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15649888", "endSection": "sections.0" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1250, "text": "iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15649888", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The yeast Saccharomyces cerevisiae contains a pair of paralogous iron-responsive transcription activators, Aft1 and Aft2. Aft1 activates the cell surface iron uptake systems in iron depletion,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16024809", "endSection": "sections.0" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1245, "text": "the absence of either Aft1 or Aft2 showed an iron-dependent increase in the amount of the remaining paralog", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16024809", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The transcription factors Aft1 and Aft2 from Saccharomyces cerevisiae regulate the expression of genes involved in iron homeostasis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648636", "endSection": "sections.0" }, { "offsetInBeginSection": 108, "offsetInEndSection": 163, "text": "iron insufficiency-responsive transcription factor Aft1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17096368", "endSection": "title" }, { "offsetInBeginSection": 225, "offsetInEndSection": 472, "text": "The mRNA levels of 14 proteins involved in iron homeostasis were shown to be increased by cisplatin. Interestingly, the expression of all 14 genes is known to be regulated by Aft1, a transcription factor activated in response to iron insufficiency", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17096368", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Aft1 is a transcriptional activator in Saccharomyces cerevisiae that responds to iron availability and regulates the expression of genes in the iron regulon", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19469713", "endSection": "sections.0" }, { "offsetInBeginSection": 224, "offsetInEndSection": 310, "text": "we found that Aft1 physically interacts with the FOB (ferrioxamine B) transporter Arn3", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19469713", "endSection": "sections.0" }, { "offsetInBeginSection": 787, "offsetInEndSection": 911, "text": "These results suggest that Aft1 interacts with Arn3 and may regulate the ubiquitination of Arn3 in the cytosolic compartment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19469713", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "The Saccharomyces cerevisiae transcription factor Aft1 is activated in iron-deficient cells to induce the expression of iron regulon genes, which coordinate the increase of iron uptake and remodel cellular metabolism to survive low-iron conditions", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439772", "endSection": "sections.0" }, { "offsetInBeginSection": 262, "offsetInEndSection": 375, "text": "Aft1 has been implicated in numerous cellular processes including cell-cycle progression and chromosome stability", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439772", "endSection": "sections.0" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1485, "text": "We demonstrate that Aft1 works in parallel with the RIM101 pH pathway and the role of Aft1 in DNA damage repair is mediated by iron. In contrast, through both directed studies and microarray transcriptional profiling, we show that the role of Aft1 in chromosome maintenance and benomyl resistance is independent of its iron regulatory role, potentially through a nontranscriptional mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439772", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Aft1p is a major iron regulator in budding yeast Saccharomyces cerevisiae. It indirectly senses cytosolic Fe status and responds by activating or repressing iron regulon genes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21361388", "endSection": "sections.0" }, { "offsetInBeginSection": 175, "offsetInEndSection": 276, "text": "Expression of components of the high-affinity system is controlled by the Aft1 transcriptional factor", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542867", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Iron-responsive transcription factor Aft1 interacts with kinetochore protein Iml3 and promotes pericentromeric cohesin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22157760", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The Saccharomyces cerevisiae iron-responsive transcription factor, Aft1, has a well established role in regulating iron homeostasis through the transcriptional induction of iron-regulon genes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22157760", "endSection": "sections.0" }, { "offsetInBeginSection": 202, "offsetInEndSection": 325, "text": "recent studies have implicated Aft1 in other cellular processes independent of iron regulation such as chromosome stability", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22157760", "endSection": "sections.0" }, { "offsetInBeginSection": 392, "offsetInEndSection": 454, "text": "Aft1 interacts with and co-localizes with kinetochore proteins", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22157760", "endSection": "sections.0" }, { "offsetInBeginSection": 837, "offsetInEndSection": 915, "text": "Our work defines a new role for Aft1 in chromosome stability and transmission.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22157760", "endSection": "sections.0" }, { "offsetInBeginSection": 693, "offsetInEndSection": 912, "text": "Our genetic network reveals that Aft1 affects a diverse range of cellular processes, including the RIM101 pH pathway, cell-wall stability, DNA damage, protein transport, chromosome stability, and mitochondrial function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439772", "endSection": "sections.0" } ] }, { "body": "Can PLN mutations lead to dilated cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20634894", "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "http://www.ncbi.nlm.nih.gov/pubmed/15336969", "http://www.ncbi.nlm.nih.gov/pubmed/15769782", "http://www.ncbi.nlm.nih.gov/pubmed/23349452", "http://www.ncbi.nlm.nih.gov/pubmed/21282613", "http://www.ncbi.nlm.nih.gov/pubmed/17019811", "http://www.ncbi.nlm.nih.gov/pubmed/12639993", "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "http://www.ncbi.nlm.nih.gov/pubmed/16235537", "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "http://www.ncbi.nlm.nih.gov/pubmed/19324307", "http://www.ncbi.nlm.nih.gov/pubmed/17998275", "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "http://www.ncbi.nlm.nih.gov/pubmed/22427649" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17851795", "o": "Dilated cardiomyopathy" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0035199", "o": "Cardiomyopathies, Dilated" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A11995504", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17895723", "o": "Dilated Cardiomyopathy" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0048982", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12058799", "o": "Cardiomyopathy, Dilated" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A13286677", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "Yes, PLN mutations can lead to dilated cardiomyopathy." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017354", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004252", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018389", "http://www.uniprot.org/uniprot/PPLA_CHICK", "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054643", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020125", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004106", "http://www.uniprot.org/uniprot/PPLA_RAT", "http://www.uniprot.org/uniprot/PPLA_RABIT", "http://www.uniprot.org/uniprot/PPLA_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004108", "http://www.uniprot.org/uniprot/PPLA_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016368", "http://www.disease-ontology.org/api/metadata/DOID:12930", "http://www.uniprot.org/uniprot/PPLA_CANFA", "http://www.uniprot.org/uniprot/PPLA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017384", "http://www.uniprot.org/uniprot/PPLA_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "yesno", "id": "5148e42cd24251bc0500003b", "snippets": [ { "offsetInBeginSection": 674, "offsetInEndSection": 826, "text": "A PLN founder mutation (43 cases) and LMNA mutations (19 cases, 16 different mutations) were most prevalent and often demonstrated a specific phenotype.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349452", "endSection": "sections.0" }, { "offsetInBeginSection": 350, "offsetInEndSection": 441, "text": "PLN mutation R14del was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "endSection": "sections.0" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1453, "text": "The PLN R14del founder mutation is present in a substantial number of patients clinically diagnosed with DCM or ARVC", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820313", "endSection": "sections.0" }, { "offsetInBeginSection": 147, "offsetInEndSection": 272, "text": "Arg(9) \u2192 Cys (R9C) and Arg(14) deletion (R14del) mutations in PLN are associated with lethal dilated cardiomyopathy in humans", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427649", "endSection": "sections.0" }, { "offsetInBeginSection": 306, "offsetInEndSection": 443, "text": "We previously reported the deletion of the highly conserved amino acid residue arginine 14 (nucleic acids 39, 40 and 41) in DCM patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "endSection": "sections.0" }, { "offsetInBeginSection": 157, "offsetInEndSection": 252, "text": "Mutations in the gene encoding PLN have been associated with idiopathic dilated cardiomyopathy;", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "endSection": "sections.0" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1565, "text": "Mutations in the PLN gene are a rare cause of heart failure, present almost exclusively in patients with dilated cardiomyopathy etiology", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22137083", "endSection": "sections.0" }, { "offsetInBeginSection": 172, "offsetInEndSection": 294, "text": "A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282613", "endSection": "sections.0" }, { "offsetInBeginSection": 465, "offsetInEndSection": 599, "text": "Complete genetic and clinical analyses were performed in a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324307", "endSection": "sections.0" }, { "offsetInBeginSection": 753, "offsetInEndSection": 1090, "text": "A candidate gene approach resulted in identification of a heterozygous deletion of arginine 14 in the gene encoding phospholamban (PLN-R14Del) segregating with dilated cardiomyopathy in the family pedigree. Mutation carriers suffered from familial dilated cardiomyopathy associated with cardiac death between the ages of 26 and 50 years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324307", "endSection": "sections.0" }, { "offsetInBeginSection": 522, "offsetInEndSection": 599, "text": "a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324307", "endSection": "sections.0" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1320, "text": "For the phospholamban (PLN) and titin cap (TTN) genes, a direct mutation screening approach was used. DNA sequence analysis of all exons showed no evidence that these genes are involved in DCM in the Newfoundland dog.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17998275", "endSection": "sections.0" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1229, "text": "two human PLN mutations, associated with either absence or sustained dephosphorylation of PLN, were linked to dilated cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17019811", "endSection": "sections.0" }, { "offsetInBeginSection": 215, "offsetInEndSection": 379, "text": "Mutations in the gene encoding PLN have been associated with dilated cardiomyopathy characterized by early onset and the presence of lethal ventricular arrhythmias.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "endSection": "sections.0" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1143, "text": "The identical PLN mutation can be associated with both mild and severe forms of dilated cardiomyopathy. Additionally, PLN mutations should be considered in late onset cardiomyopathy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17010801", "endSection": "sections.0" }, { "offsetInBeginSection": 223, "offsetInEndSection": 466, "text": "Through genetic screening of dilated cardiomyopathy patients, we identified a previously uncharacterized deletion of arginine 14 (PLN-R14Del) in the coding region of the phospholamban (PLN) gene in a large family with hereditary heart failure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16432188", "endSection": "sections.0" }, { "offsetInBeginSection": 742, "offsetInEndSection": 922, "text": "No PLN gene mutation was found in patients with DCM in Chengdu. This result indicated that PLN gene mutation may not be a common cause for DCM in the Chinese population in Chengdu.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16235537", "endSection": "sections.0" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1352, "text": "none in PLN", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15769782", "endSection": "sections.0" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1027, "text": "the recent discoveries of human PLN mutations leading to disease states.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15336969", "endSection": "sections.0" }, { "offsetInBeginSection": 612, "offsetInEndSection": 768, "text": "Strikingly, both individuals homozygous for L39stop developed dilated cardiomyopathy and heart failure, requiring cardiac transplantation at ages 16 and 27.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12639993", "endSection": "sections.0" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1377, "text": "humans lacking PLN develop lethal dilated cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12639993", "endSection": "sections.0" }, { "offsetInBeginSection": 188, "offsetInEndSection": 386, "text": "Here we report that an inherited human dilated cardiomyopathy with refractory congestive heart failure is caused by a dominant Arg --> Cys missense mutation at residue 9 (R9C) in phospholamban (PLN)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "endSection": "sections.0" } ] }, { "body": "Which is the genetic lesion associated with Huntington\u2019s disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7620118" ], "ideal_answer": [ "The genetic lesion associated with Huntington's disease is a CAG trinucleotide repeat expansion in the HD (or HTT) gene." ], "exact_answer": [ "A CAG trinucleotide repeat expansion in the HD gene" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030342", "http://www.disease-ontology.org/api/metadata/DOID:12858", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006816", "http://www.uniprot.org/uniprot/HD_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020022", "http://www.disease-ontology.org/api/metadata/DOID:630", "http://www.disease-ontology.org/api/metadata/DOID:0050325" ], "type": "factoid", "id": "5319a6e9b166e2b806000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "Early in 1993, an unstable, expanded trinucleotide repeat in a novel gene of unknown function was identified on HD chromosomes. This discovery unleased a flurry of experimentation that has established the expanded CAG repeat the almost universal cause of the characteristic neurologic symptoms and pathology of this neurodegenerative disorder of midlife onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7620118", "endSection": "abstract" } ] }, { "body": "Is corpus callosum involved in the Mowat\u2013Wilson syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "http://www.ncbi.nlm.nih.gov/pubmed/23531534", "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "http://www.ncbi.nlm.nih.gov/pubmed/15065106", "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "http://www.ncbi.nlm.nih.gov/pubmed/23243526", "http://www.ncbi.nlm.nih.gov/pubmed/12746390", "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "http://www.ncbi.nlm.nih.gov/pubmed/23322667", "http://www.ncbi.nlm.nih.gov/pubmed/16053902", "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "http://www.ncbi.nlm.nih.gov/pubmed/19215041", "http://www.ncbi.nlm.nih.gov/pubmed/20301585", "http://www.ncbi.nlm.nih.gov/pubmed/22246645", "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "http://www.ncbi.nlm.nih.gov/pubmed/17103451", "http://www.ncbi.nlm.nih.gov/pubmed/21957361", "http://www.ncbi.nlm.nih.gov/pubmed/18792984", "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "http://www.ncbi.nlm.nih.gov/pubmed/24401652", "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "http://www.ncbi.nlm.nih.gov/pubmed/16088920" ], "ideal_answer": [ "Yes, agenesis of the corpus callosum is common patients with Mowat\u2013Wilson syndrome. Other characteristic features of Mowat\u2013Wilson syndrome include typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, and eye defects." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003337", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "yesno", "id": "5314896adae131f847000001", "snippets": [ { "offsetInBeginSection": 157, "offsetInEndSection": 430, "text": " The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Mowat-Wilson syndrome in a fetus with antenatal diagnosis of short corpus callosum: advocacy for standard autopsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "endSection": "title" }, { "offsetInBeginSection": 184, "offsetInEndSection": 375, "text": "It is mainly characterized by moderate-to-severe intellectual disability, epilepsy, facial dysmorphism and various malformations including Hirschsprung disease and corpus callosum anomalies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 614, "text": "The association of a corpus callosum hypoplasia with a histological Hirschsprung disease and a typical facial gestalt allowed the guiding of genetic testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322667", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 491, "text": "The striking facial phenotype in addition to other features such as severely impaired speech, hypotonia, microcephaly, short stature, seizures, corpus callosum agenesis, congenital heart defects, hypospadias, and Hirschsprung disease are particularly important clues for the initial clinical diagnosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23243526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Mowat-Wilson syndrome is a genetic disorder characterized by a distinct facial appearance, moderate-to-severe mental retardation, microcephaly, agenesis of the corpus callosum, Hirschsprung disease, congenital heart disease, and genital anomalies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 372, "text": "It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia, and Hirschsprung disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation; a multiple congenital anomaly syndrome characterised by a typical facial gestalt, Hirschsprung disease or severe constipation, genitourinary anomaly, congenital heart defects, agenesis of corpus callosum and eye defects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 374, "text": "Agenesis or hypogenesis of the corpus callosum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301585", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 396, "text": "The anomalies may include Hirschsprung disease, heart defects, structural eye anomalies including microphthalmia, agenesis of the corpus callosum, and urogenital anomalies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19215041", "endSection": "abstract" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1418, "text": "In 11 of the 28 patients with ACC, the following diagnoses could be established: Mowat-Wilson syndrome (n = 2), Walker-Warburg syndrome (n = 1), oro-facial-digital syndrome type 1 (n = 1), and chromosomal rearrangements (n = 7), including a patient with an apparently balanced reciprocal translocation, which led to the disruption and a predicted loss of function in the FOXG1B gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18792984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 756, "text": "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1342, "text": "Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16088920", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 377, "text": "ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15065106", "endSection": "abstract" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1450, "text": "However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15065106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 470, "text": "Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12746390", "endSection": "abstract" } ] }, { "body": "Which histone modification discriminates between active and poised enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21632746", "http://www.ncbi.nlm.nih.gov/pubmed/23880941", "http://www.ncbi.nlm.nih.gov/pubmed/23595227", "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "http://www.ncbi.nlm.nih.gov/pubmed/25614629", "http://www.ncbi.nlm.nih.gov/pubmed/23166019", "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "http://www.ncbi.nlm.nih.gov/pubmed/25250711" ], "ideal_answer": [ "Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. " ], "exact_answer": [ [ "H3K4me1" ], [ "H3K27ac" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016570", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421" ], "type": "list", "id": "56c703445795f9a73e00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166019", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1471, "text": "Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166019", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 678, "text": "We used ChIP-seq to measure changes in histone H3K27 acetylation, a mark of active enhancers, to identify enhancers in myelinating rat peripheral nerve and their dynamics after demyelinating nerve injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25614629", "endSection": "abstract" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1514, "text": "However, the majority of Egr2-bound enhancers retain H3K27ac, indicating that other transcription factors maintain active enhancer status after nerve injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25614629", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 383, "text": "Recent studies using mammalian cells showed that a chromatin state signature is associated with active developmental enhancers, defined by high levels of histone H3 lysine 27 acetylation (H3K27ac) and strong depletion of H3K27 trimethylation (H3K27me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880941", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1457, "text": "Such permissive binding was largely restricted to open-chromatin regions showing histone modification marks characteristic of active enhancer and promoter regions, whereas open-chromatin regions lacking such marks did not show permissive binding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23595227", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 841, "text": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "The bivalent hypothesis posits that genes encoding developmental regulators required for early lineage decisions are poised in stem/progenitor cells by the balance between a repressor histone modification (H3K27me3), mediated by the Polycomb Repressor Complex 2 (PRC2), and an activator modification (H3K4me3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25250711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Histone H3K27ac separates active from poised enhancers and predicts developmental state", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Histone H3K27ac separates active from poised enhancers and predicts developmental state.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "title" }, { "offsetInBeginSection": 718, "offsetInEndSection": 843, "text": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1241, "text": "Furthermore, we compare the ability of eRNAs and H3K27ac to discriminate enhancer activity. We demonstrate that eRNA is more indicative of enhancer activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "endSection": "abstract" } ] }, { "body": "What are the properties of super-enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25801169", "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "http://www.ncbi.nlm.nih.gov/pubmed/25650801", "http://www.ncbi.nlm.nih.gov/pubmed/24119843", "http://www.ncbi.nlm.nih.gov/pubmed/26569311", "http://www.ncbi.nlm.nih.gov/pubmed/25263595", "http://www.ncbi.nlm.nih.gov/pubmed/25564661", "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "http://www.ncbi.nlm.nih.gov/pubmed/25686607", "http://www.ncbi.nlm.nih.gov/pubmed/24857652" ], "ideal_answer": [ "Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation. In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification. Super-enhancers thus play key roles in the control of mammalian cell identity." ], "exact_answer": [ [ "their magnitude of size" ], [ "transcription factor density" ], [ "binding of transcriptional machinery" ], [ "associated with genes driving cell differentiation" ] ], "type": "list", "id": "56c344abfedd0b786b000003", "snippets": [ { "offsetInBeginSection": 312, "offsetInEndSection": 516, "text": "Here we report that enhancer RNAs (eRNAs) identified by global nuclear run-on sequencing are extensively transcribed within super enhancers and are dynamically regulated in response to cellular signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25564661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Inflammation-sensitive super enhancers form domains of coordinately regulated enhancer RNAs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25564661", "endSection": "title" }, { "offsetInBeginSection": 650, "offsetInEndSection": 920, "text": "The expression of genes that specify cell type identity and function is associated with densely spaced clusters of active enhancers known as super-enhancers. The functions of enhancers and super-enhancers are influenced by, and affect, higher-order genomic organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25650801", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 315, "text": " Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26569311", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 784, "text": "Here we review evidence for super-enhancer involvement in cancers, complex diseases, and developmental disorders and discuss interactions between super-enhancers and cofactors/chromatin regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26569311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1102, "text": "In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 359, "text": "Super-enhancers (SEs), also known as stretch-enhancers, are a subset of enhancers especially important for genes associated with cell identity and genetic risk of disease. CD4(+) T cells are critical for host defence and autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25686607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Super-enhancers and stretch enhancers (SEs) drive expression of genes that play prominent roles in normal and disease cells, but the functional importance of these clustered enhancer elements is poorly understood, so it is not clear why genes key to cell identity have evolved regulation by such elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25801169", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 874, "text": "Super-enhancers thus provide a platform for signaling pathways to regulate genes that control cell identity during development and tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25801169", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 353, "text": "Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 669, "text": "We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "endSection": "abstract" }, { "offsetInBeginSection": 670, "offsetInEndSection": 861, "text": "New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1652, "text": "Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 735, "text": "We demonstrate that hotspots are highly enriched in large super-enhancer regions (several kilobases), which drive the early adipogenic reprogramming of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24857652", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 1059, "text": "Our results indicate that cooperativity between transcription factors at the level of hotspots as well as super-enhancers is very important for enhancer activity and transcriptional reprogramming. Thus, hotspots and super-enhancers\u00a0constitute important regulatory hubs that serve to integrate external stimuli on chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24857652", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 467, "text": "We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 631, "text": "Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1099, "text": "Super-enhancers thus play key roles in the control of mammalian cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119843", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 586, "text": "We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119843", "endSection": "abstract" }, { "offsetInBeginSection": 1644, "offsetInEndSection": 2064, "text": "Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Inflammation-sensitive super enhancers form domains of coordinately regulated enhancer RNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25564661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "NF-\u03baB directs dynamic super enhancer formation in inflammation and atherogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263595", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799994", "endSection": "title" } ] }, { "body": "What is the inheritance pattern of Li\u2013Fraumeni syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2190528", "http://www.ncbi.nlm.nih.gov/pubmed/7981072", "http://www.ncbi.nlm.nih.gov/pubmed/16772121", "http://www.ncbi.nlm.nih.gov/pubmed/9302689", "http://www.ncbi.nlm.nih.gov/pubmed/22672556", "http://www.ncbi.nlm.nih.gov/pubmed/20075382" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2961", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/679" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2961", "o": "Li Fraumeni syndrome, 151623" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/679", "o": "Li_Fraumeni_syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16615981", "o": "OMIM" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2675080", "o": "http://linkedlifedata.com/resource/umls/label/A16619828" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16615981", "o": "LI-FRAUMENI-LIKE SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16619828", "o": "LFL" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2675080", "o": "http://linkedlifedata.com/resource/umls/label/A16615981" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16619828", "o": "OMIM" } ], "ideal_answer": [ "Li-Fraumeni syndrome shows autosomal dominant inheritance." ], "exact_answer": [ "Autosomal dominant" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3012", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016864", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "factoid", "id": "52bf208003868f1b06000019", "snippets": [ { "offsetInBeginSection": 524, "offsetInEndSection": 745, "text": "It therefore appears that the LFS phenotype has been conferred by an aberrant gene, showing a dominant pattern of inheritance, which may be acting to compromise normal p53 function rather than by a mutation in p53 itself.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7981072", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1213, "text": "In addition, there seem to be predispositions to a wider range of different, but well-defined neoplasms: e.g., adenocarcinomatosis of the colon and the endometrium, or the Li-Fraumeni/SBLA syndrome. The latter shows a spectrum of sarcoma, brain tumours, breast cancer, leukaemias, lung and adenocortical cancer. The genes leading to these types of dominantly inherited predispositions appear to be the tentatively so-called tumour suppressor genes, for which the Rb gene serves as a model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2190528", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 150, "text": "he Li-Fraumeni syndrome is a rare autosomal-dominant disease whose hallmark is a predisposition to a wide range of cancers among members of a family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9302689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Li-Fraumeni Syndrome (LFS) is characterized by early-onset carcinogenesis involving multiple tumor types and shows autosomal dominant inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16772121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Li-Fraumeni-Syndrome (LFS) is an autosomal-dominant, inherited tumour predisposition syndrome associated with heterozygous germline mutations in the TP53 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22672556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Li-Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant, human familial cancer predisposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20075382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The Li-Fraumeni syndrome is a rare autosomal-dominant disease whose hallmark is a predisposition to a wide range of cancers among members of a family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9302689", "endSection": "abstract" } ] }, { "body": "Which pituitary adenoma is common cause of infertility is women?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9152623", "http://www.ncbi.nlm.nih.gov/pubmed/10649815", "http://www.ncbi.nlm.nih.gov/pubmed/6788711", "http://www.ncbi.nlm.nih.gov/pubmed/12477530", "http://www.ncbi.nlm.nih.gov/pubmed/2738821", "http://www.ncbi.nlm.nih.gov/pubmed/10649814", "http://www.ncbi.nlm.nih.gov/pubmed/23090264", "http://www.ncbi.nlm.nih.gov/pubmed/2520800", "http://www.ncbi.nlm.nih.gov/pubmed/2803131", "http://www.ncbi.nlm.nih.gov/pubmed/6868876" ], "ideal_answer": [ "Prolactinoma is a pituitary adenoma that is strongly associated with infertility in women mainly due to increased prolactin secretion causing hyperprolactinemia. Other pituitary lesions can also be associated with infertility." ], "exact_answer": [ "prolactinoma" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014930", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015175", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007247", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007246", "http://www.disease-ontology.org/api/metadata/DOID:5394", "http://www.disease-ontology.org/api/metadata/DOID:5395", "http://www.disease-ontology.org/api/metadata/DOID:5223", "http://www.disease-ontology.org/api/metadata/DOID:3829", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010911" ], "type": "factoid", "id": "514a51c2d24251bc0500005c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Prolactinoma is the most common secreting pituitary adenoma. It is typically diagnosed in women of reproductive age and is common cause of infertility.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090264", "endSection": "sections.0" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1308, "text": "Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary adenoma that stained strongly for FSH. RESULTS: Regular menses resumed soon after excision of the gonadotroph adenoma, followed by a spontaneous pregnancy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12477530", "endSection": "sections.0" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1529, "text": "CONCLUSIONS: Gonadotroph adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12477530", "endSection": "sections.0" }, { "offsetInBeginSection": 199, "offsetInEndSection": 614, "text": "Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis, occurring mostly in women and presenting most commonly with amenorrhea and galactorrhea. Causes of hyperprolactinemia include physiologic, pharmacologic and pathologic factors; pituitary adenoma is a common pathologic cause. Women may present with decreased libido, infertility, oligomenorrhea/amenorrhea and galactorrhea.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10649815", "endSection": "sections.0" }, { "offsetInBeginSection": 443, "offsetInEndSection": 788, "text": "When specific treatable underlying causes have been eliminated and in cases of severe hyperprolactinemia, the most likely cause is a prolactin (PRL)-secreting pituitary adenoma. Microadenomas should be treated medically, with a dopamine agonist, if there is an indication for therapy (such as amenorrhea, infertility or bothersome galactorrhea).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10649814", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Pregnancy in a woman with active acromegaly is very rare, because amenorrhea, due to hyperprolactinemia and disturbed pituitary gonadotropin secretion may cause infertility.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9152623", "endSection": "sections.0" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1318, "text": "Of the remaining six patients who had been investigated for infertility, no demonstrable cause of infertility was found in three. Of the other three patients, one showed evidence of bilateral tubal occlusion secondary to pelvic inflammatory disease, one has had a right ectopic pregnancy followed by two abortions, and the third patient was found to have a pituitary adenoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2738821", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Results in 136 hyperprolactinaemic women who presented with infertility, amenorrhoea, menstrual irregularities and/or galactorrhoea are reported. There was radiographic evidence of pituitary microadenoma in 21 (15.4%) patients and 5 (3.7%) had macroadenoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2803131", "endSection": "sections.0" }, { "offsetInBeginSection": 474, "offsetInEndSection": 778, "text": "Patients with pituitary adenoma had a significantly higher (p less than 0.001) baseline serum prolactin level (182 +/- 4.6 ng/ml) than those with no adenoma (59.2 +/- 4.2 ng/ml). All patients in the study were treated with bromocriptine (2.5-10 mg) to normalize serum prolactin or to achieve a pregnancy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2803131", "endSection": "sections.0" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1462, "text": "There was no significant difference in the pregnancy rate between the patients with or without pituitary adenoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2803131", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Two hyperprolactinemic infertile women, one with and one without a pituitary adenoma, who were resistant to bromocriptine treatment, were treated orally with Hachimijiogan, a Chinese herbal medicine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2520800", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Infertility caused by hyperprolactinemic amenorrhea may be complicated by pituitary adenoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6868876", "endSection": "sections.0" } ] }, { "body": "What is the role of mismatched uracil glycosylase (Mug) in DNA repair?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12184783", "http://www.ncbi.nlm.nih.gov/pubmed/12016206", "http://www.ncbi.nlm.nih.gov/pubmed/11841206", "http://www.ncbi.nlm.nih.gov/pubmed/21112870", "http://www.ncbi.nlm.nih.gov/pubmed/15474419", "http://www.ncbi.nlm.nih.gov/pubmed/10581234", "http://www.ncbi.nlm.nih.gov/pubmed/20852254", "http://www.ncbi.nlm.nih.gov/pubmed/9699633", "http://www.ncbi.nlm.nih.gov/pubmed/9489705", "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "http://www.ncbi.nlm.nih.gov/pubmed/10339434", "http://www.ncbi.nlm.nih.gov/pubmed/12531390", "http://www.ncbi.nlm.nih.gov/pubmed/12482242", "http://www.ncbi.nlm.nih.gov/pubmed/11555290" ], "ideal_answer": [ "The mismatch-specific uracil DNA glycosylase (MUG) belongs to a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. The crystal structure of the Mug repair complex points to a preference of Mug for G:U over G:T mispairs. Nonetheless, Mug does not repair U:G or T:G mismatches in vivo. Mug possesses xanthine DNA glycosylase (XDG) activity in E.coli. The repair activity of Mug is more robust against xanthine than uracil. Furthermore, Mug excises the alkylated base, 3, N(4)-ethenocytosine (epsilonC) from epsilonC:G mismatches, and may be the only enzyme in E.coli that can remove this mutagenic adduct. Thus, the principal role of Mug may be the repair of DNA damages caused by exogenous chemical agents such as chloroacetaldehyde." ], "concepts": [ "http://www.uniprot.org/uniprot/MUG_SHIBS", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016798", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004844", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053843", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043739", "http://www.uniprot.org/uniprot/MUG_CITK8", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051981", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006281" ], "type": "summary", "id": "553e07caf321868558000016", "snippets": [ { "offsetInBeginSection": 405, "offsetInEndSection": 440, "text": "XDG activity is attributable to MUG", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20852254", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 338, "text": "xanthine DNA glycosylase (XDG) activity in E. coli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20852254", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 661, "text": "The wild type MUG possesses more robust activity against xanthine than uracil and is active against all xanthine-containing DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20852254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The gene for the mismatch-specific uracil DNA glycosylase (MUG) was identified in the Escherichia coli genome as a sequence homolog of the human thymine DNA glycosylase with activity against mismatched uracil base pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20852254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581234", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1626, "text": "the principal role of Mug in E. coli may be to help repair damage to DNA caused by exogenous chemical agents such as chloroacetaldehyde", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1485, "text": "excise epsilonC. The latter activity is missing in extracts from mug cells, suggesting that Mug may be the only enzyme in E. coli that can remove this mutagenic adduct. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Base-excision of a self-complementary oligonucleotide with central G:T mismatches by the G:T/U-specific mismatch DNA glycosylase (MUG)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9699633", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1038, "text": "Mug does not repair U.G or T.G mismatches in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 339, "text": "remove 3,N(4)-ethenocytosine (epsilonC) from epsilonC.G mismatches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The human thymine-DNA glycosylase has a sequence homolog in Escherichia coli that is described to excise uracils from U.G mismatches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 928, "text": "The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3, N(4)-ethenocytosine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581234", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 699, "text": "One member of the uracil-DNA glycosylase family of repair enzymes, Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug), is reported to distinguish U:G mispairs from U:A base pairs based upon specific contacts with the mispaired guanine after flipping the target uracil out of the duplex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12482242", "endSection": "abstract" }, { "offsetInBeginSection": 1603, "offsetInEndSection": 1768, "text": "T transition in the ung mug double mutant as compared to the single ung mutant suggest that MUG may be a back-up repair enzyme to the classic uracil-DNA glycosylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15474419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "The human thymine-DNA glycosylase has a sequence homolog in Escherichia coli that is described to excise uracils from U.G mismatches (Gallinari, P., and Jiricny, J. (1996) Nature 383, 735-738) and is named mismatched uracil glycosylase (Mug).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1038, "text": "Because uracil-DNA glycosylase (Ung) and Vsr are known to repair U.G and T.G mismatches, respectively, we conclude that Mug does not repair U.G or T.G mismatches in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Role of mismatch-specific uracil-DNA glycosylase in repair of 3,N4-ethenocytosine in vivo.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15474419", "endSection": "title" }, { "offsetInBeginSection": 1485, "offsetInEndSection": 1627, "text": "Thus, the principal role of Mug in E. coli may be to help repair damage to DNA caused by exogenous chemical agents such as chloroacetaldehyde.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The role of the Escherichia coli mug protein in the removal of uracil and 3,N(4)-ethenocytosine from DNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The gene for the mismatch-specific uracil DNA glycosylase (MUG) was identified in the Escherichia coli genome as a sequence homolog of the human thymine DNA glycosylase with activity against mismatched uracil base pairs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20852254", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 701, "text": "One member of the uracil-DNA glycosylase family of repair enzymes, Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug), is reported to distinguish U:G mispairs from U:A base pairs based upon specific contacts with the mispaired guanine after flipping the target uracil out of the duplex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12482242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112870", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1037, "text": "Because uracil-DNA glycosylase (Ung) and Vsr are known to repair U.G and T.G mismatches, respectively, we conclude that Mug does not repair U.G or T.G mismatches in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521502", "endSection": "abstract" } ] }, { "body": "Which are the cardiac effects of thyronamines?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "http://www.ncbi.nlm.nih.gov/pubmed/21835056", "http://www.ncbi.nlm.nih.gov/pubmed/19273499", "http://www.ncbi.nlm.nih.gov/pubmed/20880963", "http://www.ncbi.nlm.nih.gov/pubmed/17204552", "http://www.ncbi.nlm.nih.gov/pubmed/19016324", "http://www.ncbi.nlm.nih.gov/pubmed/20739399", "http://www.ncbi.nlm.nih.gov/pubmed/17579492", "http://www.ncbi.nlm.nih.gov/pubmed/22073124", "http://www.ncbi.nlm.nih.gov/pubmed/18486124" ], "ideal_answer": [ "Thyronamines have negative chronotropy, negative inotropy; in particular thyronamines are considered negative inotropic agents", "In the heart, thyronamines cause negative chronotropy, negative inotropy,reduced cardiac output and resistance to ischemic injury." ], "exact_answer": [ [ "negative chronotropy", "lower heart rate" ], [ "negative inotropy", "negative inotropism" ], [ "resistance to ischemic injury" ], [ "reduced cardiac output" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002302", "http://www.biosemantics.org/jochem#4251308" ], "type": "list", "id": "534bb147aeec6fbd07000014", "snippets": [ { "offsetInBeginSection": 1383, "offsetInEndSection": 1653, "text": "Most recently, thyroid hormone derivatives were identified, the thyronamines which are decarboxylated thyroid hormones initiating physiological actions like lowering body temperature and heart rate, thereby acting in opposite direction to the classical thyroid hormones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835056", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 947, "text": "Intraperitoneal or central injection of 3-T(1)AM or T(0)AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20880963", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 620, "text": "Functional effects have been observed after administration of exogenous T(1)AM: in the isolated heart, a negative inotropic and chronotropic action was produced, and the resistance to ischemic injury was increased, possibly as a consequence of an action on intracellular calcium homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19016324", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 904, "text": "Octopamine, beta-phenylethylamine, and tryptamine produced a dose-dependent negative inotropic effect as shown by reduced cardiac output (IC(50)=109 microM, 159 microM, and 242 microM, respectively). In the same preparation a similar effect was produced by thyronamine and 3-iodothyronamine, with IC(50)=94 microM and 27 microM, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18486124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "A class of thyroid hormone metabolites has dramatic physiological effects on metabolism and heart rate by still-unknown mechanisms of action. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17579492", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 384, "text": "In the mouse, thyronamines act rapidly in a nongenomic fashion to initiate hypothermia and decrease cardiac output and heart rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17204552", "endSection": "abstract" } ] }, { "body": "Matuzumab has been tested for treatment of which cancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17671148", "http://www.ncbi.nlm.nih.gov/pubmed/18181050", "http://www.ncbi.nlm.nih.gov/pubmed/17126894", "http://www.ncbi.nlm.nih.gov/pubmed/19482958", "http://www.ncbi.nlm.nih.gov/pubmed/16857825", "http://www.ncbi.nlm.nih.gov/pubmed/22763610", "http://www.ncbi.nlm.nih.gov/pubmed/19276157", "http://www.ncbi.nlm.nih.gov/pubmed/20497967", "http://www.ncbi.nlm.nih.gov/pubmed/16533873", "http://www.ncbi.nlm.nih.gov/pubmed/22807624", "http://www.ncbi.nlm.nih.gov/pubmed/16622465", "http://www.ncbi.nlm.nih.gov/pubmed/22832803", "http://www.ncbi.nlm.nih.gov/pubmed/23300028", "http://www.ncbi.nlm.nih.gov/pubmed/15871762", "http://www.ncbi.nlm.nih.gov/pubmed/19433372", "http://www.ncbi.nlm.nih.gov/pubmed/19238629", "http://www.ncbi.nlm.nih.gov/pubmed/16387666", "http://www.ncbi.nlm.nih.gov/pubmed/19691369", "http://www.ncbi.nlm.nih.gov/pubmed/20978446", "http://www.ncbi.nlm.nih.gov/pubmed/15011787", "http://www.ncbi.nlm.nih.gov/pubmed/21109448", "http://www.ncbi.nlm.nih.gov/pubmed/16336753" ], "ideal_answer": [ "Matuzumab has been tested for treatment of non-small cell lung, gastric, esophageal, colorectal, primary peritoneal, pancreatic, ovarian and cervical cancers." ], "exact_answer": [ [ "non-small cell lung" ], [ "gastric" ], [ "esophageal" ], [ "colorectal" ], [ "primary peritoneal" ], [ "pancreatic" ], [ "ovarian" ], [ "cervical" ] ], "type": "list", "id": "55086ea1098a1b487b000001", "snippets": [ { "offsetInBeginSection": 1002, "offsetInEndSection": 1071, "text": " Matuzumab and panitumumab have also been studied in phase II trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "A phase I pharmacokinetic study of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22832803", "endSection": "title" }, { "offsetInBeginSection": 56, "offsetInEndSection": 261, "text": "This phase I study investigated the tolerability, safety and pharmacokinetics (PK) of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer (NSCLC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22832803", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1330, "text": "Matuzumab combined with paclitaxel was generally well tolerated in patients with advanced NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22832803", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 680, "text": "This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22807624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763610", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "BACKGROUND: To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanced gastric and esophagogastric adenocarcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763610", "endSection": "abstract" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1188, "text": "Matuzumab and panitumumab have also been evaluated in phase II trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978446", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "INTRODUCTION: This randomized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophago-gastric cancer: a randomised, multicentre open-label phase II study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20497967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin, cisplatin and capecitabine (ECX) chemotherapy in untreated advanced oesophago-gastric (OG) cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20497967", "endSection": "abstract" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 1634, "text": " CONCLUSION: Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20497967", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 817, "text": "In all studies, the patients had different types of advanced carcinoma - mainly colon, rectal and pancreatic cancer. They received matuzumab as multiple 1-hour intravenous infusions in a wide range of dosing regimens (development dataset: from 400 mg every 3 weeks to 2000 mg in the first week followed by 1600 mg weekly; evaluation dataset: from 100 mg weekly to 800 mg weekly). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19691369", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1473, "text": " Other anti-EGFR monoclonal antibodies, such as panitumumab, matuzumab, nimotuzumab, and ch806, are in different stages of development for the treatment of advanced NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19482958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276157", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Antibodies targeting epidermal growth factor receptor (EGFR) have proven to be effective in patients with non-small cell lung cancer (NSCLC) that express EGFR. We recently published a phase I study of weekly matuzumab plus paclitaxel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276157", "endSection": "abstract" }, { "offsetInBeginSection": 1678, "offsetInEndSection": 1837, "text": "Our data suggest that EGFR expression and KRAS mutation status is predictive for clinical response to matuzumab +/- paclitaxel in patients with advanced NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19238629", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19238629", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 957, "text": "Therefore, these first successes led to the development of several drugs including monoclonal antibodies (trastuzumab, panitumumab, matuzumab), TK inhibitors targeting one receptor as well as TK pan-inhibitors (lapatinib, HKI 272, PKI 166, EKB-569, AEE-788), currently assessed through clinical trials worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19433372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Antibodies to the epidermal growth factor receptor in non small cell lung cancer: current status of matuzumab and panitumumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671148", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Matuzumab and panitumumab are antibodies against the epidermal growth factor receptor (EGFR) that are being evaluated in several malignancies including non-small cell lung cancer (NSCLC). In phase I trials of single-agent matuzumab in patients with EGFR-positive cancer, three tumor responses were documented in esophageal squamous cell carcinoma as well as colorectal carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17126894", "endSection": "title" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1379, "text": "CONCLUSIONS: Matuzumab at the dose and schedule selected is well tolerated. In this population of very heavily pretreated patients with epithelial ovarian and primary peritoneal malignancies, there was no evidence of significant clinical activity when matuzumab was administered as monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17126894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16622465", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 547, "text": " Three groups of chemotherapy-naive advanced pancreatic adenocarcinoma patients (n=17) received escalating doses of matuzumab (400 mg weekly, 800 mg biweekly, or 800 mg weekly) and gemcitabine (1000 mg m-2 weekly in weeks 1-3 of each 4-week cycle). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16622465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16533873", "endSection": "title" }, { "offsetInBeginSection": 303, "offsetInEndSection": 458, "text": "This phase I study assessed the tolerability, pharmacokinetics and efficacy of the combination of matuzumab and paclitaxel in patients with advanced NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16533873", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 430, "text": "Other anti-EGFR monoclonal antibodies (panitunumab, matuzumab) are currently evaluated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16387666", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 305, "text": "It is the target for a class of agents at the forefront of development for the treatment of colorectal cancer, ie, the anti-EGFR monoclonal antibodies, which include cetuximab, panitumumab, and matuzumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16336753", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1002, "text": "Two other monoclonal antibodies, matuzumab (EMD 72000) and panitumumab (ABG-EGF), also have shown activity against EGFR-expressing CRC but are still in the early stage of clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15871762", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 287, "text": "Matuzumab is currently undergoing phase II clinical trials for gastric, cervical, pancreatic and ovarian cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15011787", "endSection": "abstract" } ] }, { "body": "Which are the synonyms of prostate-specific antigen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19079621" ], "ideal_answer": [ "Prostate-specific antigen (PSA) is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases which is produced by epithelial cells of both normal and malignant prostate tissue. PSA is an important marker for the diagnosis of prostate cancer. PSA is also known as human kallikrein-related peptidase 3 (hK3).", "Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases. (PMID: 19079621)" ], "exact_answer": [ [ "human kallikrein-related peptidase 3" ], [ "hK3" ] ], "concepts": [ "http://www.uniprot.org/uniprot/KLK3_MACFA", "http://www.uniprot.org/uniprot/KLK2_CAVPO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017430", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020840", "http://www.uniprot.org/uniprot/KLK3_HUMAN" ], "type": "list", "id": "5171651e8ed59a060a000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Evidence for the novel expression of human kallikrein-related peptidase 3, prostate-specific antigen, in the brain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19079621", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19079621", "endSection": "sections.0" } ] }, { "body": "What is the lipid droplet used for in the cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26121906", "http://www.ncbi.nlm.nih.gov/pubmed/25189622", "http://www.ncbi.nlm.nih.gov/pubmed/25132820", "http://www.ncbi.nlm.nih.gov/pubmed/24394544", "http://www.ncbi.nlm.nih.gov/pubmed/25894691", "http://www.ncbi.nlm.nih.gov/pubmed/25110833" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12002602", "o": "MTHU008985" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1848739", "o": "http://linkedlifedata.com/resource/umls/label/A12002602" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12002602", "o": "Lipid droplets in granulocytes" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1848739", "o": "http://linkedlifedata.com/resource/umls/label/A12002602" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12002602", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16505206", "o": "GO:0034430" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2612536", "o": "http://linkedlifedata.com/resource/umls/label/A16505206" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2612536", "o": "http://linkedlifedata.com/resource/umls/label/A16505206" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16505206", "o": "lipid droplet outer lipid monolayer" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11988246", "o": "MTHU008988" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1848740", "o": "http://linkedlifedata.com/resource/umls/label/A11988246" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11988246", "o": "Lipid droplets in basal keratinocytes" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1848740", "o": "http://linkedlifedata.com/resource/umls/label/A11988246" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInCellType", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://purl.uniprot.org/tissues/12" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000B" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000C" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/12", "o": "Adipocytes" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000B", "o": "Perilipin-1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/12", "o": "Adipocyte" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000C", "o": "Lipid droplet-associated protein" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInCellType", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://purl.uniprot.org/tissues/12" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834009" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834009", "o": "Lipid droplet-associated protein" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834008", "o": "Perilipin-1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834008" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11988246", "o": "OMIM" } ], "ideal_answer": [ "Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands." ], "exact_answer": [ "lipid storage and lipid mobilization" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D066292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005811", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ], "type": "factoid", "id": "56b397a98525abca1e000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Eukaryotic cells store excess fatty acids as neutral lipids, predominantly triacylglycerols and sterol esters, in organelles termed lipid droplets (LDs) that bulge out from the endoplasmic reticulum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25894691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26121906", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 782, "text": "Cells store fatty acids (FAs) as triacylglycerol and package them into cytoplasmic lipid droplets (LDs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25132820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Lipid droplets are found in all cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25110833", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 348, "text": "Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24394544", "endSection": "abstract" } ] }, { "body": "What is the function of circular RNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "http://www.ncbi.nlm.nih.gov/pubmed/24039610", "http://www.ncbi.nlm.nih.gov/pubmed/24609083", "http://www.ncbi.nlm.nih.gov/pubmed/25404635", "http://www.ncbi.nlm.nih.gov/pubmed/7678559" ], "ideal_answer": [ "Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. The biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression.", "Circular RNAs are new players in regulation of post transcriptional gene expression. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. This new type of transcript might represent a novel aspect of gene expression and hold some interesting clues about the splicing mechanism. Here we determine the structure of these novel transcripts, showing that they correspond to circular RNA molecules containing only exons in genomic order." ], "exact_answer": [ "Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "factoid", "id": "56c58ceeb04e159d0e000004", "snippets": [ { "offsetInBeginSection": 276, "offsetInEndSection": 430, "text": "Here we determine the structure of these novel transcripts, showing that they correspond to circular RNA molecules containing only exons in genomic order.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7678559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039610", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 654, "text": "Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039610", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 789, "text": "These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039610", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 392, "text": "Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 989, "text": " For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "An unexpectedly large fraction of genes in metazoans (human, mouse, zebrafish, worm, fruit fly) express high levels of circularized RNAs containing canonical exons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24609083", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1090, "text": "A minority of genes in S. pombe and P. falciparum have documented examples of canonical alternative splicing, making it unlikely that all circular RNAs are by-products of alternative splicing or 'piggyback' on signals used in alternative RNA processing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24609083", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1321, "text": "Circular RNA may be an ancient, conserved feature of eukaryotic gene expression programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24609083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 430, "text": "CircRNAs are largely generated from exonic or intronic sequences, and reverse complementary sequences or RNA-binding proteins (RBPs) are necessary for circRNA biogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 758, "text": "Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1088, "text": "Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 791, "text": "Circular RNAs can function as templates for viroid and viral replication, as intermediates in RNA processing reactions, as regulators of transcription in cis, as snoRNAs, and as miRNA sponges", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404635", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 917, "text": "Circular RNAs can function as templates for viroid and viral replication, as intermediates in RNA processing reactions, as regulators of transcription in cis, as snoRNAs, and as miRNA sponges. Herein, we review the breadth of circular RNAs, their biogenesis and metabolism, and their known and anticipated functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404635", "endSection": "abstract" } ] }, { "body": "Can NXY-059 be used for treatment of acute ischemic stroke patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17408618", "http://www.ncbi.nlm.nih.gov/pubmed/21651461", "http://www.ncbi.nlm.nih.gov/pubmed/11239186", "http://www.ncbi.nlm.nih.gov/pubmed/18369171", "http://www.ncbi.nlm.nih.gov/pubmed/17068304", "http://www.ncbi.nlm.nih.gov/pubmed/17975102", "http://www.ncbi.nlm.nih.gov/pubmed/19074479", "http://www.ncbi.nlm.nih.gov/pubmed/19631615", "http://www.ncbi.nlm.nih.gov/pubmed/18416999", "http://www.ncbi.nlm.nih.gov/pubmed/17420989", "http://www.ncbi.nlm.nih.gov/pubmed/23419732", "http://www.ncbi.nlm.nih.gov/pubmed/22709256", "http://www.ncbi.nlm.nih.gov/pubmed/16467546", "http://www.ncbi.nlm.nih.gov/pubmed/17478741", "http://www.ncbi.nlm.nih.gov/pubmed/17579658", "http://www.ncbi.nlm.nih.gov/pubmed/23109881", "http://www.ncbi.nlm.nih.gov/pubmed/17687131", "http://www.ncbi.nlm.nih.gov/pubmed/12848592", "http://www.ncbi.nlm.nih.gov/pubmed/17244778", "http://www.ncbi.nlm.nih.gov/pubmed/18673209", "http://www.ncbi.nlm.nih.gov/pubmed/19167593" ], "ideal_answer": [ "No. 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective." ], "exact_answer": "no", "type": "yesno", "id": "54d62faf3706e89528000003", "snippets": [ { "offsetInBeginSection": 402, "offsetInEndSection": 704, "text": "Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23109881", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1035, "text": "This occurred during 1993-2006, when the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419732", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 364, "text": "The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22709256", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 739, "text": "OKN-007 is a proprietary compound that has had extensive commercial development (designated as NXY-059) for another indication, acute ischemic stroke, and after extensive clinical studies was shown to lack efficacy for this indication but was shown to be very safe for human use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21651461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "NXY-059, a polar compound with limited transport across the blood-brain barrier, has demonstrated neuroprotection in several animal models of acute ischemic stroke but failed to confirm clinical benefit in the second phase III trial (SAINT-II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19631615", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 488, "text": "NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19167593", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 385, "text": "We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074479", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 320, "text": " In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18673209", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 852, "text": " In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18416999", "endSection": "abstract" }, { "offsetInBeginSection": 1920, "offsetInEndSection": 2010, "text": "CONCLUSIONS: NXY-059 is ineffective for treatment of AIS within 6 hours of symptom onset. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18369171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "BACKGROUND AND PURPOSE: The SAINT I trial that showed a significant benefit of the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke trials: a shift toward good functional outcome on the 7-category modified Rankin scale (mRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17975102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17687131", "endSection": "abstract" }, { "offsetInBeginSection": 1773, "offsetInEndSection": 1895, "text": "CONCLUSIONS: NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17687131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17579658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The SAINT II Trial, a large randomized multicenter clinical trial of the putative neuroprotectant, NXY-059, failed to demonstrate a treatment benefit in acute ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17478741", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 844, "text": "The positive results from the first Stroke-Acute-Ischaemic-NXY-Treatment (SAINT-I) trial of the free-radical spin-trap drug, NXY-059, which followed many of the STAIR guidelines, reinvigorated enthusiasm in neuroprotection, but the SAINT-II trial did not replicate the positive effect on the same primary prespecified outcome measure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17420989", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 613, "text": "NXY-059, a free radical spin trap agent, was felt by many to have followed these criteria and it was recently shown to improve outcome in AIS patients in the SAINT I trial. However, the repeat, SAINT II trial was a neutral study, the results of which cast doubt on neuroprotection as a viable strategy for AIS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17408618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17244778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "BACKGROUND AND PURPOSE: NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17068304", "endSection": "abstract" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1527, "text": "CONCLUSIONS: NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17068304", "endSection": "abstract" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 2095, "text": "CONCLUSIONS: The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16467546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17687131", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 487, "text": "NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19167593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17687131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17579658", "endSection": "abstract" } ] }, { "body": "Is flibanserin effetive for Hypoactive Sexual Desire Disorder? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20646181", "http://www.ncbi.nlm.nih.gov/pubmed/23421417", "http://www.ncbi.nlm.nih.gov/pubmed/25659981", "http://www.ncbi.nlm.nih.gov/pubmed/25187905", "http://www.ncbi.nlm.nih.gov/pubmed/24281236", "http://www.ncbi.nlm.nih.gov/pubmed/22727480" ], "ideal_answer": [ "Yes, flibanserin, a novel serotonin (5-HT)(1A) agonist and 5-HT(2A) antagonist, has been shown to increase sexual desire and reduce distress in women with Hypoactive Sexual Desire Disorder." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4266735", "http://www.biosemantics.org/jochem#4266735", "http://www.disease-ontology.org/api/metadata/DOID:13868" ], "type": "yesno", "id": "56bb6b0eac7ad1001900000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25659981", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Flibanserin is a novel multifunctional serotonin agonist and antagonist (MSAA) that improves sexual functioning in premenopausal women who suffer from reduced sexual interest and desire.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25659981", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 518, "text": "Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25187905", "endSection": "abstract" }, { "offsetInBeginSection": 1455, "offsetInEndSection": 1717, "text": "CONCLUSIONS: In naturally postmenopausal women with HSDD, flibanserin, compared with placebo, has been associated with improvement in sexual desire, improvement in the number of SSEs, and reduced distress associated with low sexual desire, and is well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24281236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "INTRODUCTION: Flibanserin is a mixed 5-HT1A agonist/5-HT2A antagonist that has been developed for the treatment of hypoactive sexual desire disorder in women", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23421417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "BACKGROUND: Flibanserin, a novel serotonin (5-HT)(1A) agonist and 5-HT(2A) antagonist, has been shown to increase sexual desire and reduce distress in women with Hypoactive Sexual Desire Disorder (HSDD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 431, "text": "Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25187905", "endSection": "abstract" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1982, "text": "Sexual function adverse events across flibanserin groups were generally comparable to placebo.Although these studies were not designed or powered to compare sexual function outcomes, results suggested a potential benefit of flibanserin on sexual function, particularly on female sexual desire, and provided a rationale to evaluate the efficacy of flibanserin as a treatment for female hypoactive sexual desire disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20646181", "endSection": "abstract" } ] }, { "body": "List available biomedical question answering systems.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17990503", "http://www.ncbi.nlm.nih.gov/pubmed/23244628", "http://www.ncbi.nlm.nih.gov/pubmed/18274647" ], "ideal_answer": [ "We live in an age of access to more information than ever before. The exponential growth in the volume of publications in the biomedical domain has made it impossible for an individual to keep pace with the advances. Thus, there is a need for intelligent information retrieval systems that can summarize relevant and reliable textual sources to satisfy a user's query. Question answering is a specialized type of information retrieval with the aim of returning precise short answers to queries posed as natural language questions. This accentuates the need for fast and accurate biomedical question answering systems. In this paper we introduce INDOC -- a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed. Increased access to information allows for more informed and empowered researchers, while information overload becomes an increasingly serious risk. INDOC displays the results in clusters to help the user arrive the most relevant set of documents quickly. Evaluation was done against the standard OHSUMED test collection. We present a review and comparison of three biomedical question answering systems: askHERMES, EAGLi ( http://eagl.unige.ch/EAGLi/ ), and HONQA ( http://services.hon.ch/cgi-bin/QA10/qa.pl ). ", "askHERMES, EAGLi, HONQA and INDOC." ], "exact_answer": [ [ "askHERMES" ], [ "EAGLi" ], [ "HONQA" ], [ "INDOC" ] ], "type": "list", "id": "55414c65472cfd8617000001", "snippets": [ { "offsetInBeginSection": 401, "offsetInEndSection": 775, "text": "Question answering is a specialized type of information retrieval with the aim of returning precise short answers to queries posed as natural language questions. We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.askhermes.org/), EAGLi (http://eagl.unige.ch/EAGLi/), and HONQA (http://services.hon.ch/cgi-bin/QA10/qa.pl)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Question processing and clustering in INDOC: a biomedical question answering system", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18274647", "endSection": "title" }, { "offsetInBeginSection": 427, "offsetInEndSection": 815, "text": "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed. INDOC displays the results in clusters to help the user arrive the most relevant set of documents quickly. Evaluation was done against the standard OHSUMED test collection. Our system achieves high accuracy and minimizes user effort", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18274647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Question processing and clustering in INDOC: a biomedical question answering system.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18274647", "endSection": "title" }, { "offsetInBeginSection": 423, "offsetInEndSection": 579, "text": "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18274647", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 663, "text": "We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244628", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 582, "text": "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18274647", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 775, "text": "We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.askhermes.org/), EAGLi (http://eagl.unige.ch/EAGLi/), and HONQA (http://services.hon.ch/cgi-bin/QA10/qa.pl).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244628", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 776, "text": "We present a review and comparison of three biomedical question answering systems: askHERMES (http://www.askhermes.org/), EAGLi (http://eagl.unige.ch/EAGLi/), and HONQA (http://services.hon.ch/cgi-bin/QA10/qa.pl).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244628", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 581, "text": "In this paper we introduce INDOC--a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18274647", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 737, "text": "Onelook is a portal for online definitions, and MedQA is a question answering system that automatically generates short texts to answer specific biomedical questions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17990503", "endSection": "abstract" } ] }, { "body": "Which dediodinases are present in kidney?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15072569", "http://www.ncbi.nlm.nih.gov/pubmed/9794474", "http://www.ncbi.nlm.nih.gov/pubmed/3595535", "http://www.ncbi.nlm.nih.gov/pubmed/7768329", "http://www.ncbi.nlm.nih.gov/pubmed/3197644" ], "ideal_answer": [ "Type 1 and Type 3 deiodinases are both present in liver" ], "exact_answer": [ [ "Type 1 deiodinase" ], [ "Tipe 3 deiodinase" ] ], "type": "list", "id": "517a8c238ed59a060a000042", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15072569", "endSection": "sections.0" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1039, "text": "Co-expression of the deiodinases was also found in the kidney.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15072569", "endSection": "sections.0" }, { "offsetInBeginSection": 437, "offsetInEndSection": 485, "text": "high ID-I activities were found in liver, kidney", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7768329", "endSection": "sections.0" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1392, "text": "the kidney microsome 5'-deiodinase is type I.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3595535", "endSection": "sections.0" } ] }, { "body": "What is the presumed key event in Fanconi anemia pathogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22675617", "http://www.ncbi.nlm.nih.gov/pubmed/15601828", "http://www.ncbi.nlm.nih.gov/pubmed/19609304", "http://www.ncbi.nlm.nih.gov/pubmed/20937699", "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "http://www.ncbi.nlm.nih.gov/pubmed/22258451", "http://www.ncbi.nlm.nih.gov/pubmed/15383454" ], "ideal_answer": [ "Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links. Failure of FANCD2 monoubiquitination by the nuclear FA protein complex has a severe impact on the DNA repair functions of cells." ], "exact_answer": [ "FANCD2 monoubiquitination" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "factoid", "id": "54edf72c94afd61504000013", "snippets": [ { "offsetInBeginSection": 92, "offsetInEndSection": 278, "text": "A key event in FA pathway activation is the monoubiquitylation of the FA complementation group I (FANCI)-FANCD2 (ID) complex by FA complementation group L (FANCL), an E3 ubiquitin ligase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19609304", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 746, "text": "Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. Eight FA-associated genes have been identified so far, the products of which function in the FA/BRCA pathway. A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15383454", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 744, "text": " Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 377, "text": "This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258451", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 747, "text": "Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 370, "text": "A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15383454", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 562, "text": "The key event of the FA pathway is dependent on an eight-protein core complex (CC), required for the monoubiquitination of each member of the FANCD2-FANCI complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22675617", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 387, "text": "FA proteins (FancA/C/E/F/G/L) form a multiprotein complex, which is responsible for DNA damage-induced FancD2 monoubiquitination, a key event for cellular resistance to DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15601828", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 279, "text": "A key event in FA pathway activation is the monoubiquitylation of the FA complementation group I (FANCI)-FANCD2 (ID) complex by FA complementation group L (FANCL), an E3 ubiquitin ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937699", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 369, "text": "A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15383454", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 376, "text": "This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258451", "endSection": "abstract" } ] }, { "body": "What is the effect of Allopurinol on asphyxia in neonates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16428356", "http://www.ncbi.nlm.nih.gov/pubmed/17162192", "http://www.ncbi.nlm.nih.gov/pubmed/22564301", "http://www.ncbi.nlm.nih.gov/pubmed/22102633", "http://www.ncbi.nlm.nih.gov/pubmed/9445490", "http://www.ncbi.nlm.nih.gov/pubmed/16778717", "http://www.ncbi.nlm.nih.gov/pubmed/12436031", "http://www.ncbi.nlm.nih.gov/pubmed/20167117" ], "ideal_answer": [ "Allopurinol was shown in a number of clinical trial to be safe and effective for treatment of neonatal asphyxia. Allopurinol improves short-term and long-term clinical outcomes of neonatal asphyxia. Allopurinol should be administered as soon as possible. Postulated mechanism of allopurinol action in this setting is prevention of hypoxia-perfusion injury by reduction of free radical formation." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001238", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001237", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007231", "http://www.disease-ontology.org/api/metadata/DOID:11088", "http://www.biosemantics.org/jochem#4273300", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000493" ], "type": "summary", "id": "515df1d4298dcd4e5100002b", "snippets": [ { "offsetInBeginSection": 1203, "offsetInEndSection": 1473, "text": "Potential neuroprotective strategies targeting different pathways leading to neuronal cell death in response to hypoxic-ischemic insult have been investigated: hypothermia, erythropoietin, iminobiotin, deferioxamine, magnesium, allopurinol, xenon, melatonin and statins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22564301", "endSection": "sections.0" }, { "offsetInBeginSection": 138, "offsetInEndSection": 260, "text": "Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102633", "endSection": "sections.0" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1771, "text": "There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95%CI 0.17 to 0.94).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102633", "endSection": "sections.0" }, { "offsetInBeginSection": 1785, "offsetInEndSection": 1910, "text": "The reported data may suggest a (neuro)protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102633", "endSection": "sections.0" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1356, "text": "The asphyxiated newborns treated with allopurinol had better neurologic and neurodevelopmental outcome at 12 or more months of age.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17162192", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "In newborn infants, allopurinol is being tested as a free radical scavenger to prevent brain damage caused by reperfusion and oxygenation after perinatal hypoxia and ischemia (birth asphyxia).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16778717", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16428356", "endSection": "title" }, { "offsetInBeginSection": 364, "offsetInEndSection": 468, "text": "The analysis showed an unaltered (high) mortality and morbidity in the infants treated with allopurinol.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16428356", "endSection": "sections.0" }, { "offsetInBeginSection": 482, "offsetInEndSection": 596, "text": "Allopurinol treatment started postnatally was too late to reduce the early reperfusion induced free radical surge.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16428356", "endSection": "sections.0" }, { "offsetInBeginSection": 323, "offsetInEndSection": 432, "text": "One randomized trial of allopurinol showed short-term benefits but was too small to test death or disability.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12436031", "endSection": "sections.0" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1279, "text": "No toxic side effects of ALLO were detected.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9445490", "endSection": "sections.0" }, { "offsetInBeginSection": 2087, "offsetInEndSection": 2235, "text": "This study suggests a beneficial effect of ALLO treatment on free radical formation, CBV, and electrical brain activity, without toxic side effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9445490", "endSection": "sections.0" } ] }, { "body": "Is recommended the use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7477166", "http://www.ncbi.nlm.nih.gov/pubmed/20668034", "http://www.ncbi.nlm.nih.gov/pubmed/14500064", "http://www.ncbi.nlm.nih.gov/pubmed/12643405", "http://www.ncbi.nlm.nih.gov/pubmed/8389710", "http://www.ncbi.nlm.nih.gov/pubmed/8633935", "http://www.ncbi.nlm.nih.gov/pubmed/12079930", "http://www.ncbi.nlm.nih.gov/pubmed/12800543", "http://www.ncbi.nlm.nih.gov/pubmed/1859661", "http://www.ncbi.nlm.nih.gov/pubmed/10343261", "http://www.ncbi.nlm.nih.gov/pubmed/18290900", "http://www.ncbi.nlm.nih.gov/pubmed/16719939", "http://www.ncbi.nlm.nih.gov/pubmed/3872103", "http://www.ncbi.nlm.nih.gov/pubmed/12213743", "http://www.ncbi.nlm.nih.gov/pubmed/8594265" ], "ideal_answer": [ "Currently there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047549", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001026" ], "type": "yesno", "id": "53267871d6d3ac6a3400000a", "snippets": [ { "offsetInBeginSection": 1517, "offsetInEndSection": 1615, "text": "Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20668034", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 835, "text": "We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18290900", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1417, "text": "There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12800543", "endSection": "abstract" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1282, "text": "Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome. Routine use after coronary surgery is thus not recommended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12213743", "endSection": "abstract" }, { "offsetInBeginSection": 1625, "offsetInEndSection": 1835, "text": "Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8594265", "endSection": "abstract" }, { "offsetInBeginSection": 1978, "offsetInEndSection": 2225, "text": "Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7477166", "endSection": "abstract" }, { "offsetInBeginSection": 1367, "offsetInEndSection": 1483, "text": "Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8389710", "endSection": "abstract" } ] }, { "body": "When is the protein NFL a biomarker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24571714", "http://www.ncbi.nlm.nih.gov/pubmed/24479774", "http://www.ncbi.nlm.nih.gov/pubmed/24242746", "http://www.ncbi.nlm.nih.gov/pubmed/24073237", "http://www.ncbi.nlm.nih.gov/pubmed/17290105", "http://www.ncbi.nlm.nih.gov/pubmed/16894110", "http://www.ncbi.nlm.nih.gov/pubmed/24935984", "http://www.ncbi.nlm.nih.gov/pubmed/14694036", "http://www.ncbi.nlm.nih.gov/pubmed/25934855", "http://www.ncbi.nlm.nih.gov/pubmed/24523921", "http://www.ncbi.nlm.nih.gov/pubmed/23827424", "http://www.ncbi.nlm.nih.gov/pubmed/25192482", "http://www.ncbi.nlm.nih.gov/pubmed/21197541", "http://www.ncbi.nlm.nih.gov/pubmed/23763388", "http://www.ncbi.nlm.nih.gov/pubmed/22496755", "http://www.ncbi.nlm.nih.gov/pubmed/26273687", "http://www.ncbi.nlm.nih.gov/pubmed/20132991", "http://www.ncbi.nlm.nih.gov/pubmed/24941067", "http://www.ncbi.nlm.nih.gov/pubmed/23718879", "http://www.ncbi.nlm.nih.gov/pubmed/23529999", "http://www.ncbi.nlm.nih.gov/pubmed/17596713" ], "ideal_answer": [ "Neurofilament light protein (NFL), may be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS).\nNeurofilament light chain is a prognostic biomarker in neurological disorders such as amyotrophic lateral sclerosis, frontotemporal degeneration, axonal injury, late-onset cerebellar ataxia, multiple sclerosis and head trauma." ], "type": "summary", "id": "56e844c442442bac75000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934855", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "CSF neurofilament light chain reflects corticospinal tract degeneration in ALS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26273687", "endSection": "title" }, { "offsetInBeginSection": 207, "offsetInEndSection": 356, "text": "Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26273687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24935984", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25192482", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 166, "text": "Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24242746", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 324, "text": "We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523921", "endSection": "abstract" }, { "offsetInBeginSection": 1921, "offsetInEndSection": 2065, "text": "FL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523921", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1612, "text": "Analysis of MBP, NFL and GFAp provides direct means to measure tissue damage and is a useful addition to our methods for evaluation of MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24571714", "endSection": "abstract" }, { "offsetInBeginSection": 1921, "offsetInEndSection": 2090, "text": " The association of prolonged CSF NFL increase in boxers with impairment of processing speed is an interesting observation, which needs to be verified in larger studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24941067", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 321, "text": "neurofilament light chain (NfL) levels in CSF of relapsing remitting (RR) patients with MS were normalized by natalizumab treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23763388", "endSection": "abstract" }, { "offsetInBeginSection": 1671, "offsetInEndSection": 1838, "text": "Our results suggest that NfL is superior over NfH(SMI) (35) as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23763388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Increased neurofilament light chain blood levels in neurodegenerative neurological diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24073237", "endSection": "title" }, { "offsetInBeginSection": 1505, "offsetInEndSection": 1746, "text": "Our data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24073237", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1639, "text": " We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23529999", "endSection": "abstract" }, { "offsetInBeginSection": 1775, "offsetInEndSection": 1872, "text": "CSF T-tau, GFAP, and NFL are differently altered across different neurologic diseases in children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23827424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23718879", "endSection": "title" }, { "offsetInBeginSection": 1808, "offsetInEndSection": 1920, "text": "he marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23718879", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1250, "text": "High levels of NFL also correlated with the presence of an AD biomarker pattern defined by A\u03b242/P-tau and T-tau. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24479774", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1417, "text": "Increased CSF levels of T-tau, NFL, GFAP, and S-100B in>80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496755", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 386, "text": "eurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21197541", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1204, "text": "A CSF profile with higher levels of NFL, Abeta42, and CSF/serum albumin ratio may indicate neuropathological and vascular events in depression etiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20132991", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1519, "text": " At present we cannot recommend CSF NfH and NfL levels for use as a screening test in the diagnosis of dementia because of the rather small effect size. However, both neurofilament proteins may be of value for targeted investigation of some patients with FTLD, SVD and AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17596713", "endSection": "abstract" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1228, "text": "Differences in CSF biomarker profiles might reflect differential involvement of neurofilaments and tau in FTD and EAD. The subgroup of FTD patients with high CSF neurofilament levels may have a different neuropathological substrate and future studies addressing this specific issue are needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17290105", "endSection": "abstract" }, { "offsetInBeginSection": 1358, "offsetInEndSection": 1640, "text": "Increased levels of neurofilament light chain and tau and decreased levels of 3-methoxy-4-hydroxyphenylethyleneglycol were associated with high accuracy levels in differentiating the cerebellar subtype of multiple-system atrophy from idiopathic late-onset cerebellar ataxia (LOCA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16894110", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1139, "text": "Increased level of NFL is a general feature of MS, indicating continuous axonal damage during the entire course of the disease with the most profound damage during acute relapses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14694036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14694036", "endSection": "title" } ] }, { "body": "Is protein CXCR4 used as a prognostic marker of cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20061818", "http://www.ncbi.nlm.nih.gov/pubmed/23822165", "http://www.ncbi.nlm.nih.gov/pubmed/23650783", "http://www.ncbi.nlm.nih.gov/pubmed/22473623", "http://www.ncbi.nlm.nih.gov/pubmed/21234386", "http://www.ncbi.nlm.nih.gov/pubmed/22075627", "http://www.ncbi.nlm.nih.gov/pubmed/23936528", "http://www.ncbi.nlm.nih.gov/pubmed/23213054", "http://www.ncbi.nlm.nih.gov/pubmed/23359227", "http://www.ncbi.nlm.nih.gov/pubmed/26221287", "http://www.ncbi.nlm.nih.gov/pubmed/24650104", "http://www.ncbi.nlm.nih.gov/pubmed/23395387" ], "ideal_answer": [ "Yes, the chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer." ], "exact_answer": "yes", "type": "yesno", "id": "56e68967edfc094c1f000002", "snippets": [ { "offsetInBeginSection": 1568, "offsetInEndSection": 1722, "text": "Aberrant overexpression of CXCR4 is associated with worse overall survival, adenocarcinoma histology, distant metastasis, lymph node involvement in NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26221287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "CXCR4 belongs to a family of G protein-coupled cell surface receptors and has been proved to a prognostic marker in a various tumors, including esophageal squamous cell cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23822165", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 838, "text": "The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650104", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1138, "text": "The chemokine receptor CXCR4 that has been shown to be implicated in PDAC tumorigenicity and aggressiveness could serve as a prognostic marker for survival after a curative-intent surgery and was associated with the pattern of tumour recurrence (distant versus local relapse).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23650783", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 322, "text": "XCR4 promotes tumor growth, angiogenesis and metastasis, and is a prognostic marker in a number of different types of tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395387", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 115, "text": "CXCR4 has been identified as a prognostic marker for acute myeloid leukemia (AML) and other malignancies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23213054", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 319, "text": "The chemokine receptor CXCR4 has been found to be a prognostic marker in various types of cancer, including breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Upregulated expression of C-X-C chemokine receptor 4 is an independent prognostic predictor for patients with gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23936528", "endSection": "title" }, { "offsetInBeginSection": 1662, "offsetInEndSection": 1766, "text": "detection of CXCR4 expression will be helpful for predicting prognosis for patients with gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23936528", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 269, "text": "The chemokine receptor CXCR4 is a marker of metastatic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473623", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1596, "text": "High CXCR4 level in cancer specimens independently predicts a poor outcome for patients with node-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473623", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1190, "text": "Univariate and multivariate analyses demonstrated that the high levels of nuclear CXCR4 and CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CLM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075627", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 307, "text": "The chemokine receptor CXCR4 has been implicated in sarcoma development and has been found to be a prognostic marker for poor clinical outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21234386", "endSection": "abstract" }, { "offsetInBeginSection": 1598, "offsetInEndSection": 1756, "text": "high CXCR4 expression is correlated to shorter DFS and could be used as a prognostic marker in order to stratify melanoma patients at higher progression risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20061818", "endSection": "abstract" } ] }, { "body": "How does thyroid hormone regulate SR-Ca2+ ATPase (SERCA) protein in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "http://www.ncbi.nlm.nih.gov/pubmed/22975595", "http://www.ncbi.nlm.nih.gov/pubmed/18658259", "http://www.ncbi.nlm.nih.gov/pubmed/10198194", "http://www.ncbi.nlm.nih.gov/pubmed/11470472", "http://www.ncbi.nlm.nih.gov/pubmed/17560116", "http://www.ncbi.nlm.nih.gov/pubmed/9312172", "http://www.ncbi.nlm.nih.gov/pubmed/18274800", "http://www.ncbi.nlm.nih.gov/pubmed/11145561", "http://www.ncbi.nlm.nih.gov/pubmed/2142022", "http://www.ncbi.nlm.nih.gov/pubmed/1415533", "http://www.ncbi.nlm.nih.gov/pubmed/20232113", "http://www.ncbi.nlm.nih.gov/pubmed/17317766", "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "http://www.ncbi.nlm.nih.gov/pubmed/8779840", "http://www.ncbi.nlm.nih.gov/pubmed/1827123", "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "http://www.ncbi.nlm.nih.gov/pubmed/16595628", "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "http://www.ncbi.nlm.nih.gov/pubmed/15242794" ], "ideal_answer": [ "The thyroid hormone (TH) induced regulation of SERCA is mediated both by non-genomic and genomic actions.\nGenomic actions are mediated by the binding of T(3) receptors (TRs) to the thyroid response elements in the SERCA promotor and result in increased gene expression. \nThyroid hormone increases the transcription of SERCA 2 through three thyroid hormone response elements. \nData show that the regulation of cardiac SERCA by thyroid hormone is made at the pretranslational and possibly transcriptional level \nTR\u03b21 is shown to be coupled to the expression of SERCA in the heart\nAn increase of TR expression in the hypertrophied heart has been show to result in increased SERCA expression.\nInhibition of TR\u03b11 by dronedarone does not change the expression of SERCA in the heart\nFindings show that SERCA 2 gene expression is regulated by TR isoform-specific interactions with transcription factor (MEF-2) \nHypothyroidism is accompanied by decreased expression of SERCA in the heart. T3 increases expression of the cardiac SERCA\nTH treatment can reverse the reduction in the ratio of SERCA to phospholamban expression which is found in postinfarcted hearts\nTH treatment results in increased expression of SERCA in hearts from banded rats" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0015349", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.biosemantics.org/jochem#4275389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000609", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.biosemantics.org/jochem#4250045", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.uniprot.org/uniprot/AT2A2_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006590", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE", "http://www.uniprot.org/uniprot/AT2A2_MOUSE" ], "type": "summary", "id": "5159a306d24251bc050000a1", "snippets": [ { "offsetInBeginSection": 850, "offsetInEndSection": 1200, "text": "Furthermore, using specific inhibitors of the TH-activated kinases, we show that the long-term effects of TH on the expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), alpha- and beta-myosin heavy chain (MHC) and cell growth are reverted, implying that what is initiated as a non-genomic action of the hormone interfaces with genomic effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20232113", "endSection": "sections.0" }, { "offsetInBeginSection": 688, "offsetInEndSection": 850, "text": "Hypothyroid neonates showed increased cholesterol levels and decreased expression of D1 in liver and of Serca-2 in heart, which were normalized with T3 treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975595", "endSection": "sections.0" }, { "offsetInBeginSection": 587, "offsetInEndSection": 891, "text": "ERCA2 transcript and protein levels were reduced in FOG-2 transgenic hearts, and FOG-2 overexpression impaired T3-mediated SERCA2 expression in cultured cardiomyocytes. FOG-2 physically interacts with thyroid hormone receptor-alpha1 and abrogated even high levels of T3-mediated SERCA2 promoter activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18658259", "endSection": "sections.0" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1516, "text": "A marked elevation of the expression of beta-MHC and a reduced ratio of SERCA/Phospholamban were found in viable myocardium of AMI hearts, which was prevented by TH", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18274800", "endSection": "sections.0" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1682, "text": "After TH treatment, AMI-THYR hearts expressed 71% alpha-MHC and 29% beta-MHC, P<0.05 versus SHAM and AMI and the ratio of SERCA/PLB was increased by 2.0-fold, P<0.05 versus SHAM and AMI.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560116", "endSection": "sections.0" }, { "offsetInBeginSection": 405, "offsetInEndSection": 535, "text": "Because the binding of T(3) occupied receptors to the thyroid response elements in the SERCA promotor can increase gene expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17317766", "endSection": "sections.0" }, { "offsetInBeginSection": 1620, "offsetInEndSection": 1792, "text": "These results demonstrate that increasing TR expression in the hypertrophied heart is associated with an improvement in contractile function and increased SERCA expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17317766", "endSection": "sections.0" }, { "offsetInBeginSection": 609, "offsetInEndSection": 933, "text": "Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16595628", "endSection": "sections.0" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1471, "text": "Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16595628", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 525, "text": "Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "endSection": "sections.0" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1050, "text": "while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "endSection": "sections.0" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1141, "text": "the postnatal switch from beta- to alpha-myosin heavy chain (beta- and alpha-MHC, respectively) gene expression and the increase of SERCA-2a mRNA expression did not occur in the ventricular myocardium of either the transgenic (thyroid destroyed) or nontransgenic (intact thyroid) offspring of hypothyroid mothers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15242794", "endSection": "sections.0" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1373, "text": "In addition, TR cotransfection and treatment with the TRbeta1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "endSection": "sections.0" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1454, "text": "dditionally, in T3-deprived samples alpha-sarcomeric actinin and SERCA-2 protein levels were reduced to 65.6 +/- 3% (P < 0.0001) and 74.1 +/- 4% (P=0.005), respectively, when compared with the T3-supplemented group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11470472", "endSection": "sections.0" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1277, "text": "even mild chronic myocardial thyrotoxicosis, such as may occur in human hyperthyroidism, can cause tachycardia and associated changes in high energy phosphate compounds independent of an increase in SERCA II and alpha-MHC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11145561", "endSection": "sections.0" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1009, "text": "Myocytes from banded hearts treated with T4 were hypertrophied but had increased concentrations of alpha-MHC and SERCA proteins", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9312172", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Thyroid hormone (T3) increases the transcription of the sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) gene (SERCA 2) through three thyroid hormone response elements.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "endSection": "sections.0" }, { "offsetInBeginSection": 743, "offsetInEndSection": 1218, "text": "MEF-2a in combination with either T3R alpha 1 or T3R beta 1 isoforms resulted in a 2.5-fold increase in SERCA 2 transgene expression in the absence of T3. Addition of T3 did not induce any further increase in SERCA 2 expression when T3R alpha 1 and MEF-2a expression vectors were cotransfected. In contrast, in the presence of T3R beta 1 and MEF-2, the addition of T3 increased chlorampenicol acetyltransferase activity by an additional 2.2-fold to a total 5.5-fold increase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "endSection": "sections.0" }, { "offsetInBeginSection": 1746, "offsetInEndSection": 1902, "text": "Our findings point to T3R isoform-specific interactions with a cell type-specific transcription factor (MEF-2) in the regulation of SERCA 2 gene expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "endSection": "sections.0" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1305, "text": "These data are consistent with pretranslational and possibly transcriptional level effect of thyroid hormone on the cardiac SR Ca2+ pump gene (SERCA 2)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8779840", "endSection": "sections.0" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1153, "text": "These data demonstrate that T3 increases expression of the cardiac SR Ca2+ pump, that the effect can be localized to the cardiomyocyte, and that the effect is dependent on thyroid hormone receptors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8779840", "endSection": "sections.0" }, { "offsetInBeginSection": 210, "offsetInEndSection": 341, "text": "Thyroid hormone receptor (TR), a transcriptional activator, affected the regulation of gene expression of MHC and SR Ca(2+)-ATPase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "endSection": "sections.0" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1037, "text": "The thyroid hormone responsiveness of SR Ca2(+)-ATPase mRNA has been previously established.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2142022", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The mRNA encoding the sarcoplasmic reticulum (SR) Ca2+ ATPase is highly influenced by thyroid hormone (T3) in the hearts of intact animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1827123", "endSection": "sections.0" }, { "offsetInBeginSection": 127, "offsetInEndSection": 351, "text": "Direct cellular effects of thyroid hormone have been implicated in modulating the expression of the myosin heavy chain (MHC) genes and the slow sarcoplasmic reticulum calcium adenosine triphosphatase (SR Ca(2+)-ATPase) gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1415533", "endSection": "sections.0" } ] }, { "body": "Which trancription factor activates the betalain pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25436858", "http://www.ncbi.nlm.nih.gov/pubmed/19791510" ], "ideal_answer": [ "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway." ], "exact_answer": [ "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway." ], "type": "factoid", "id": "56d138fe3975bb303a000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436858", "endSection": "title" }, { "offsetInBeginSection": 617, "offsetInEndSection": 769, "text": "Some putative MYB, bHLH, and environmental stress-responsive transcription factor binding sites were detected in the PaDOD1 and PaDOD2 promoter regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19791510", "endSection": "abstract" } ] }, { "body": "List common symptoms of patients with the DOORS syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24291220" ], "ideal_answer": [ "DOORS syndrome is a constellation of deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures. It is a rare autosomal recessive disorder of unknown cause." ], "exact_answer": [ [ "deafness" ], [ "onychodystrophy" ], [ "osteodystrophy" ], [ "mental retardation" ], [ "seizures" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013568", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "list", "id": "530e1c985937551c09000004", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 162, "text": "Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 577, "text": "Through a search of available case studies and communication with collaborators, we identified families that included at least one individual with at least three of the five main features of the DOORS syndrome: deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" } ] }, { "body": "Which is the most well-accepted method for Down syndrome non-invasive prenatal diagnosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25218787", "http://www.ncbi.nlm.nih.gov/pubmed/22500647", "http://www.ncbi.nlm.nih.gov/pubmed/22839575", "http://www.ncbi.nlm.nih.gov/pubmed/17697502", "http://www.ncbi.nlm.nih.gov/pubmed/12498419", "http://www.ncbi.nlm.nih.gov/pubmed/21303301", "http://www.ncbi.nlm.nih.gov/pubmed/22038362", "http://www.ncbi.nlm.nih.gov/pubmed/18207470", "http://www.ncbi.nlm.nih.gov/pubmed/23371439", "http://www.ncbi.nlm.nih.gov/pubmed/22773950" ], "ideal_answer": [ "Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR). This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues. It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.", "This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. Moreover, the differential methylation for each locus could be seen during the whole pregnant period." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004314", "http://www.disease-ontology.org/api/metadata/DOID:14250", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011296" ], "type": "summary", "id": "56f403d009dd18d46b000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Potential of syncytiotrophoblasts isolated from the cervical mucus for early non-invasive prenatal diagnosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218787", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Maternal serum protein profile and immune response protein subunits as markers for non-invasive prenatal diagnosis of trisomy 21, 18, and 13", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371439", "endSection": "title" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1565, "text": "Maternal serum protein profiling using proteomics may allow non-invasive diagnostic testing for the most common trisomies and may complement ultrasound-based methods to more accurately determine pregnancies with fetal aneuploidies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. The use of circulating foetal DNA for the non-invasive prenatal detection of foetal chromosomal aneuploidies is challenging as foetal DNA represents a minor fraction of maternal plasma DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773950", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 704, "text": "Using massively parallel sequencing, foetal trisomies 21, 13 and 18 have been detected from maternal plasma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773950", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1167, "text": "These developments suggest that the analysis of foetal DNA in maternal plasma would play an increasingly important role in future obstetrics practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773950", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 393, "text": "Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22500647", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 644, "text": "Cell-free fetal RNA was extracted from the plasma of peripheral blood from 121 women 9-20 weeks of pregnancy. Five single nucleotide polymorphism (SNP) loci in PLAC4 gene were analyzed by reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), followed by capillary electrophoresis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Non-invasive prenatal diagnosis of trisomy 21 by dosage ratio of fetal chromosome-specific epigenetic markers in maternal plasma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038362", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038362", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 867, "text": "Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038362", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1817, "text": "It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038362", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1131, "text": "Preliminary reports indicate that the detection of fetal aneuploidies might be possible using epigenetically modified genes, e.g. maspin on chromosome 18. Additionally, an exiting recent development is that it might be feasible to detect Down syndrome via the quantitative assessment of placentally derived cell-free mRNA of chromosome-21-specific genes such as PLAC4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18207470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Candidate epigenetic biomarkers for non-invasive prenatal diagnosis of Down syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17697502", "endSection": "title" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1286, "text": "Next, it was shown that the methylation status of chorionic villus sample DNA from first trimester pregnancies matched the hypermethylated state of term placenta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17697502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Non-invasive prenatal diagnosis of trisomy 21 by reverse transcriptase multiplex ligation-dependent probe amplification.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303301", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "To study whether pregnant women would like to be informed if sex chromosomal abnormalities (SCA) were suspected with the non-invasive prenatal diagnosis of fetal Down syndrome (the NIFTY) test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22839575", "endSection": "abstract" } ] }, { "body": "Is the H3K4me3 histone mark related to transcriptional initiation or elongation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22855832", "http://www.ncbi.nlm.nih.gov/pubmed/21435340", "http://www.ncbi.nlm.nih.gov/pubmed/22132139", "http://www.ncbi.nlm.nih.gov/pubmed/23284292", "http://www.ncbi.nlm.nih.gov/pubmed/22768981", "http://www.ncbi.nlm.nih.gov/pubmed/23355544", "http://www.ncbi.nlm.nih.gov/pubmed/18682226", "http://www.ncbi.nlm.nih.gov/pubmed/22904080" ], "ideal_answer": [ "H3K4me3 is associated with transcriptionally active genes, but its function in the transcription process is still unclear. It is well known to occur in the promoter region of genes for transcription activation but its levels correlate positively with the antisense expression levels of the associated sense genes implying that it may be also involved in the activation of antisense transcription. Although it is mostly associated with transcription initiation H3K4me3 levels determine the efficiency of transcription elongation." ], "exact_answer": [ "transcriptional initiation" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020871", "http://www.biosemantics.org/jochem#4250488", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042925", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050436", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051697", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051758", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035181", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048348", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061805", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015533", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035582", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035581" ], "type": "factoid", "id": "512d2fff5274a5fb07000006", "snippets": [ { "offsetInBeginSection": 659, "offsetInEndSection": 782, "text": "The histone marks appeared mainly in generic regions and were enriched around the transcription start sites (TSSs) of genes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23355544", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Trimethylation of histone H3 Lys 4 (H3K4me3) is a mark of active and poised promoters.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22855832", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Histone H3 lysine 4 trimethylation (H3K4me3) is well known to occur in the promoter region of genes for transcription activation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768981", "endSection": "sections.0" }, { "offsetInBeginSection": 348, "offsetInEndSection": 422, "text": "3'-H3K4me3 is associated with ~15% of protein-coding genes in both tissues", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768981", "endSection": "sections.0" }, { "offsetInBeginSection": 697, "offsetInEndSection": 912, "text": "Furthermore, 3'-H3K4me3 modification levels correlate positively with the antisense expression levels of the associated sense genes, implying that 3'-H3K4me3 is involved in the activation of antisense transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768981", "endSection": "sections.0" }, { "offsetInBeginSection": 654, "offsetInEndSection": 853, "text": "Among these are forms of histone 3 that are mono- or tri-methylated at lysine 4 (H3K4me1 or H3K4me3, respectively), which bind preferentially to promoter and enhancer elements in the mammalian genome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435340", "endSection": "sections.0" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1156, "text": "we find that H3K4me1 and H3K4me3 are enriched at transcriptional start sites in the genome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435340", "endSection": "sections.0" }, { "offsetInBeginSection": 1676, "offsetInEndSection": 1734, "text": "H3K4me1 and H3K4me3 generally mark cis regulatory elements", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21435340", "endSection": "sections.0" } ] }, { "body": "What does polyadenylate-binding protein 4 (PABP4) bind to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23938467", "http://www.ncbi.nlm.nih.gov/pubmed/18467502", "http://www.ncbi.nlm.nih.gov/pubmed/21518916", "http://www.ncbi.nlm.nih.gov/pubmed/22884093", "http://www.ncbi.nlm.nih.gov/pubmed/23300856", "http://www.ncbi.nlm.nih.gov/pubmed/14717712", "http://www.ncbi.nlm.nih.gov/pubmed/21940797", "http://www.ncbi.nlm.nih.gov/pubmed/18753244", "http://www.ncbi.nlm.nih.gov/pubmed/20943973", "http://www.ncbi.nlm.nih.gov/pubmed/22896784", "http://www.ncbi.nlm.nih.gov/pubmed/15676026" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q13310", "o": "http://linkedlifedata.com/resource/#_5131333331300025" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_5131333331300025", "o": "APP1" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5131333331300022", "o": "iPABP" }, { "p": 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{ "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3831883", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3839562", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3845291", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8596234", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8606969", "o": "MeSH" } ], "ideal_answer": [ "PABP4 binds mRNA poly(A) tails." ], "exact_answer": [ "PABP4 binds mRNA poly(A) tails." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006378", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026723", 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poly(A) binding protein (PABP) is known to exist in five different isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Cytoplasmic poly(A)-binding proteins (PABPs) regulate mRNA stability and translation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22896784", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 420, "text": " poly(A) binding proteins 1 and 4 (PABPC1 and PABPC4)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20943973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Cytoplasmic poly(A) binding protein 4 (PABPC4) is an RNA-processing protein that plays an important role in the regulation of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Cytoplasmic poly(A) binding protein 4 ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884093", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 363, "text": "poly(A)-binding protein (PABP) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15676026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Poly(A) binding protein (PABP) binds mRNA poly(A) tails ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14717712", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 355, "text": "Using mass spectrometry sequencing we identified poly(A) binding proteins-1 and -4 (PABP1 and PABP4) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The poly(A)-binding protein (PABP) is an important translation initiation factor that binds to the polyadenylated 3' end of mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18753244", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 252, "text": "A family of cytoplasmic poly(A)-binding proteins (PABPs) bind the poly(A) tail and can regulate mRNA translation and stability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21518916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Human PABP binds AU-rich RNA via RNA-binding domains 3 and 4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14717712", "endSection": "title" } ] }, { "body": "What is the average diameter of intermediate filaments?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18523546", "http://www.ncbi.nlm.nih.gov/pubmed/17289402", "http://www.ncbi.nlm.nih.gov/pubmed/22126386", "http://www.ncbi.nlm.nih.gov/pubmed/22848616", "http://www.ncbi.nlm.nih.gov/pubmed/18726512", "http://www.ncbi.nlm.nih.gov/pubmed/15373777", "http://www.ncbi.nlm.nih.gov/pubmed/19559031", "http://www.ncbi.nlm.nih.gov/pubmed/19656809", "http://www.ncbi.nlm.nih.gov/pubmed/21669844", "http://www.ncbi.nlm.nih.gov/pubmed/2264817", "http://www.ncbi.nlm.nih.gov/pubmed/16458019" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0059267", "o": "Filaments, Intermediate" } ], "ideal_answer": [ "Intermediate filaments have an average diameter of 10 nanometers (nm)." ], "exact_answer": [ "10 nanometers", "10 nm" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007382" ], "type": "factoid", "id": "515db3d8298dcd4e51000015", "snippets": [ { "offsetInBeginSection": 553, "offsetInEndSection": 801, "text": "Negative staining showed that supernatants from the centrifugation assays contained protofilaments, protofibrils and short particles (less than 300 nm), but pellets contained long filaments (greater than 1 micron) with an average diameter of 10 nm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2264817", "endSection": "sections.0" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1197, "text": "Ultrastructurally, rhabdoid cells showed paranuclear aggregates and whorls of intermediate filaments with a 9-10 nm diameter.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22126386", "endSection": "sections.0" }, { "offsetInBeginSection": 437, "offsetInEndSection": 650, "text": "After removing IFs by calcination, electron microscopy revealed hollow silica nanotubes several micrometers long, with outer diameters of 35-55 nm and an average inner diameter of 10 nm (comparable to that of IFs)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656809", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Intermediate filaments are filaments 10\u2009nm in diameter that make up an important component of the cytoskeleton in most metazoan taxa.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669844", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Neurofilaments (NFs) are essential cytoskeletal filaments that impart mechanical integrity to nerve cells. They are assembled from three distinct molecular mass proteins that bind to each other to form a 10-nm-diameter filamentous rod with sidearm extensions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19559031", "endSection": "sections.0" }, { "offsetInBeginSection": 108, "offsetInEndSection": 312, "text": "Scanning tunneling microscope (STM) and transmission electron microscope (TEM) micrographs showed that acidic keratins and basic keratins can assemble into dimers and further into 10 nm filamentsin vitro.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18726512", "endSection": "sections.0" }, { "offsetInBeginSection": 151, "offsetInEndSection": 289, "text": "Intermediate in diameter between microtubules and microfilaments, IFs constitute the third cytoskeletal filament system of metazoan cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17289402", "endSection": "sections.0" }, { "offsetInBeginSection": 613, "offsetInEndSection": 720, "text": "Just above the bulb, the filaments are characterized by a diameter of 100 Angstroms and a low-density core.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16458019", "endSection": "sections.0" }, { "offsetInBeginSection": 1656, "offsetInEndSection": 2023, "text": "Further, using cryo-transmission electron microscopy on native, fully hydrated, vitreous epidermis we show that the subfilametous keratin electron density pattern consists, both in corneocytes and in viable keratinocytes, of one axial subfilament surrounded by an undetermined number of peripheral subfilaments forming filaments with a diameter of approximately 8 nm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15373777", "endSection": "sections.0" } ] }, { "body": "Elaborate on the association between Genomic Regulatory Blocks (GRBs) and target genes", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "http://www.ncbi.nlm.nih.gov/pubmed/19969543" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0027269", "o": "D001244" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0027288", "o": "D001244" } ], "ideal_answer": [ "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005809", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053263" ], "type": "summary", "id": "56a3a8c7496b62f23f000009", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 557, "text": "Recent functional studies have demonstrated that many microRNAs (miRNAs) are expressed by RNA polymerase II in a specific spatiotemporal manner during the development of organisms and play a key role in cell-lineage decisions and morphogenesis. They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 492, "text": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1386, "text": "We show evidence that GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1706, "text": "GRB targets are genes with a number of unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 538, "text": "Insect genomes contain larger blocks of conserved gene order (microsynteny) than would be expected under a random breakage model of chromosome evolution. We present evidence that microsynteny has been retained to keep large arrays of highly conserved noncoding elements (HCNEs) intact. These arrays span key developmental regulatory genes, forming genomic regulatory blocks (GRBs). We recently described GRBs in vertebrates, where most HCNEs function as enhancers and HCNE arrays specify complex expression programs of their target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 544, "text": "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "BACKGROUND: Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 722, "text": "GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. The tight regulation of target genes, complex arrangement of regulatory inputs, and the differential responsiveness of genes in the region call for the examination of fundamental rules governing transcriptional activity in GRBs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" } ] }, { "body": "Which therapeutic interventions for sarcopenia have been applied", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20852673", "http://www.ncbi.nlm.nih.gov/pubmed/20223299", "http://www.ncbi.nlm.nih.gov/pubmed/24079768" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00557388", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_name", "s": "http://data.linkedct.org/resource/condition/11756", "o": "Sarcopenia" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/condition/11756", "o": "Condition #11756 (Sarcopenia)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00557388", "o": "Trial NCT00557388" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00475501", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00475501", "o": "Trial NCT00475501" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00748696", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00748696", "o": "Trial NCT00748696" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00529659", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00529659", "o": "Trial NCT00529659" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00240981", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00240981", "o": "Trial NCT00240981" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00690534", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00690534", "o": "Trial NCT00690534" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00183040", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00183040", "o": "Trial NCT00183040" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00730184", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00730184", "o": "Trial NCT00730184" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00190060", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00190060", "o": "Trial NCT00190060" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00465153", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00465153", "o": "Trial NCT00465153" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00744094", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00744094", "o": "Trial NCT00744094" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00357214", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00357214", "o": "Trial NCT00357214" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00260442", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00260442", "o": "Trial NCT00260442" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00174135", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00174135", "o": "Trial NCT00174135" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00473902", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://data.linkedct.org/resource/linkedct/acronym", "s": "http://data.linkedct.org/resource/trials/NCT00473902", "o": "OTR" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00473902", "o": "Trial NCT00473902" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00725166", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://data.linkedct.org/resource/linkedct/acronym", "s": "http://data.linkedct.org/resource/trials/NCT00725166", "o": "CERA" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00725166", "o": "Trial NCT00725166" } ], "ideal_answer": [ "The main bulk of experimental pharmacological interventions addressing the clinical problem of frailty have been focused on the use of hormones, as replacement therapy in subjects with low or normal circulating basal levels of the hormone. Results have been disappointing, except for the case of testosterone that have shown some benefits. The effectiveness of other potential therapeutic interventions (antioxidants, anti-inflammatory agents, nutritional supplements) appears to be limited or has not been explored in detail until now." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016033", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055948" ], "type": "summary", "id": "52fb20a32059c6d71c00005d", "snippets": [ { "offsetInBeginSection": 817, "offsetInEndSection": 1353, "text": "The main bulk of experimental pharmacological interventions addressing the clinical problem of frailty have been focused on the use of hormones, as replacement therapy in subjects with low or normal circulating basal levels of the hormone. Results have been disappointing, except for the case of testosterone that have shown some benefits. The effectiveness of other potential therapeutic interventions (antioxidants, anti-inflammatory agents, nutritional supplements) appears to be limited or has not been explored in detail until now.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24079768", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 854, "text": "effective treatment options are still under investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20852673", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 326, "text": "Design of therapeutic interventions for geriatric frailty has been challenging and may be because of inadequate understanding of its biological underpinnings", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20223299", "endSection": "abstract" } ] }, { "body": "What is the genetic basis of progeria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24019745", "http://www.ncbi.nlm.nih.gov/pubmed/17677003", "http://www.ncbi.nlm.nih.gov/pubmed/2687104", "http://www.ncbi.nlm.nih.gov/pubmed/6214719", "http://www.ncbi.nlm.nih.gov/pubmed/21217880", "http://www.ncbi.nlm.nih.gov/pubmed/18256394", "http://www.ncbi.nlm.nih.gov/pubmed/9309268", "http://www.ncbi.nlm.nih.gov/pubmed/1128606" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18467534", "o": "C536073" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2931103", "o": "http://linkedlifedata.com/resource/umls/label/A18467534" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18467534", "o": "Hutchinson Gilford progeria syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18467534", "o": "MeSH" } ], "ideal_answer": [ "Hutchinson-Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke. \tThe genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:37", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014898", "http://www.disease-ontology.org/api/metadata/DOID:0050325", "http://www.disease-ontology.org/api/metadata/DOID:3911", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011371", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003057", "http://www.disease-ontology.org/api/metadata/DOID:5688", "http://www.disease-ontology.org/api/metadata/DOID:630" ], "type": "summary", "id": "52d783bf98d0239505000001", "snippets": [ { "offsetInBeginSection": 28, "offsetInEndSection": 224, "text": "Hutchinson-Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217880", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 496, "text": "The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217880", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 699, "text": "At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217880", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 227, "text": "Hutchinson-Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256394", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 495, "text": "The genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256394", "endSection": "abstract" } ] }, { "body": "What is the function of cryptochrome-1 in mouse?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19858287", "http://www.ncbi.nlm.nih.gov/pubmed/16731656", "http://www.ncbi.nlm.nih.gov/pubmed/12381662", "http://www.ncbi.nlm.nih.gov/pubmed/16061665", "http://www.ncbi.nlm.nih.gov/pubmed/19833968", "http://www.ncbi.nlm.nih.gov/pubmed/12495442", "http://www.ncbi.nlm.nih.gov/pubmed/15047890", "http://www.ncbi.nlm.nih.gov/pubmed/23471982", "http://www.ncbi.nlm.nih.gov/pubmed/16777965", "http://www.ncbi.nlm.nih.gov/pubmed/21236481", "http://www.ncbi.nlm.nih.gov/pubmed/19405859", "http://www.ncbi.nlm.nih.gov/pubmed/22952936", "http://www.ncbi.nlm.nih.gov/pubmed/22140039", "http://www.ncbi.nlm.nih.gov/pubmed/22170608", "http://www.ncbi.nlm.nih.gov/pubmed/18974860", "http://www.ncbi.nlm.nih.gov/pubmed/20100521", "http://www.ncbi.nlm.nih.gov/pubmed/15980066", "http://www.ncbi.nlm.nih.gov/pubmed/20825493", "http://www.ncbi.nlm.nih.gov/pubmed/12121621", "http://www.ncbi.nlm.nih.gov/pubmed/20023637", "http://www.ncbi.nlm.nih.gov/pubmed/22669941", "http://www.ncbi.nlm.nih.gov/pubmed/14712914" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3879881", "o": "function" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A7582711", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0542341", "o": "http://linkedlifedata.com/resource/umls/label/A7582711" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1506397", "o": "http://linkedlifedata.com/resource/umls/label/A16996234" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16996234", "o": "cryptochrome 1 (photolyase-like) protein, mouse" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0288450", "o": "http://linkedlifedata.com/resource/umls/label/A12066546" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12066546", "o": "cryptochrome 1" } ], "ideal_answer": [ "Cryptochrome-1 (Cry1) is an essential component of the central and peripheral circadian clocks for generation of circadian rhythms in mice." ], "exact_answer": [ "component of the central and peripheral circadian clocks for generation of circadian rhythms in mice" ], "type": "factoid", "id": "51680a6d298dcd4e51000063", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "Malfunction of the circadian clock has been linked to the pathogenesis of a variety of diseases. We show that mice lacking the core clock components Cryptochrome-1 (Cry1) and Cryptochrome-2 (Cry2) (Cry-null mice) show salt-sensitive hypertension due to abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal gland.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20023637", "endSection": "sections.0" }, { "offsetInBeginSection": 313, "offsetInEndSection": 554, "text": "The Cryptochrome 1 and 2 genes are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel-running behavior and lack of rhythmic clock gene expression in mCry1/mCry2 double-mutant mice in constant darkness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12121621", "endSection": "sections.0" }, { "offsetInBeginSection": 442, "offsetInEndSection": 1222, "text": "Among the components driving the mammalian circadian clock are the Period 1 and 2 (mPer1 and mPer2) and Cryptochrome 1 and 2 (mCry1 and mCry2) genes. A mutation in the mPer2 gene leads to a gradual loss of circadian rhythmicity in mice kept in constant darkness (DD). Here we show that inactivation of the mCry2 gene in mPer2 mutant mice restores circadian rhythmicity and normal clock gene expression patterns. Thus, mCry2 can act as a nonallelic suppressor of mPer2, which points to direct or indirect interactions of PER2 and CRY2 proteins. In marked contrast, inactivation of mCry1 in mPer2 mutant mice does not restore circadian rhythmicity but instead results in complete behavioral arrhythmicity in DD, indicating different effects of mCry1 and mCry2 in the clock mechanism", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12381662", "endSection": "sections.0" }, { "offsetInBeginSection": 289, "offsetInEndSection": 574, "text": "Cryptochrome 1 and 2 gene products act in the negative feedback loop and are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel running behaviour and absence of cyclic clock gene expression in mCry1/mCry2 double mutant mice in constant darkness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14712914", "endSection": "sections.0" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1423, "text": ", when mCry-deficient mice are housed in normal light-dark cycles, a single non-circadian peak in neuronal activity can be detected in SCN slices prepared two hours after the beginning of the day. This light-induced increase in electric activity of the SCN suggests that deletion of the mCry genes converts the core oscillator in an hour-glass-like timekeeper and may explain why in normal day-night cycles mCry-deficient mice show apparently normal behaviour.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14712914", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Cryptochrome 1 and 2 act as essential components of the central and peripheral circadian clocks for generation of circadian rhythms in mammals", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15980066", "endSection": "sections.0" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1500, "text": "cryptochrome-1 mRNA was found in DA cells, immunocytochemistry was extended to other components of the circadian clock machinery. This analysis showed that DA cells contain the most common clock-related proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15047890", "endSection": "sections.0" }, { "offsetInBeginSection": 193, "offsetInEndSection": 335, "text": "Cryptochrome 1 and cryptochrome 2 proteins are core components of the mammalian circadian clock and mice mutated in both genes are arrhythmic.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16061665", "endSection": "sections.0" }, { "offsetInBeginSection": 417, "offsetInEndSection": 779, "text": "a domain in the extreme C terminus of BMAL1 that plays an essential role in the rhythmic control of E-box-mediated circadian transcription. Remarkably, the last 43 aa of BMAL1 are required for transcriptional activation, as well as for association with the circadian transcriptional repressor CRYPTOCHROME 1 (CRY1), depending on the coexistence of CLOCK protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16777965", "endSection": "sections.0" }, { "offsetInBeginSection": 624, "offsetInEndSection": 671, "text": "circadian rhythm protein cryptochrome 1 (CRY1).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19405859", "endSection": "sections.0" }, { "offsetInBeginSection": 1576, "offsetInEndSection": 1678, "text": "CRY1 is a master regulator of circadian rhythm that regulates the extracellular calcification of MSCs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19405859", "endSection": "sections.0" }, { "offsetInBeginSection": 362, "offsetInEndSection": 1010, "text": "Studying mouse fibroblasts, we demonstrated that the nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1). In mouse livers, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK destabilized cryptochromes and altered circadian rhythms, and mice in which the AMPK pathway was genetically disrupted showed alterations in peripheral clocks. Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19833968", "endSection": "sections.0" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1242, "text": "Cytoplasmic hnRNP D levels displayed a pattern that was reciprocal to the mcry1 oscillation. Knockdown of hnRNP D stabilized mcry1 mRNA and resulted in enhancement of the oscillation amplitude and a slight delay of the phase. Our results suggest that hnRNP D plays a role as a fine regulator contributing to the mcry1 mRNA turnover rate and the modulation of circadian rhythm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19858287", "endSection": "sections.0" }, { "offsetInBeginSection": 546, "offsetInEndSection": 867, "text": "more than three mutations of conserved PER2 residues impaired not only binding to CRY1 but also subsequent nuclear translocation, although mutations of non-conserved residues did not affect interaction with CRY1. Thus, the conserved amino acid residues of 1179-1198 in PER2 are apparently responsible for binding to CRY1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100521", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "Cryptochrome 1 and 2 (Cry1 and Cry2) are considered essential for generating circadian rhythms in mammals. The role of Cry1 and Cry2 in circadian rhythm expression and acute light-induced suppression of pineal melatonin was assessed using Cry1 and Cry2 double-deficient mice (Cry1(-/-) /Cry2(-/-) ) developed from the C3H strain that synthesizes melatonin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20825493", "endSection": "sections.0" }, { "offsetInBeginSection": 119, "offsetInEndSection": 278, "text": "Cryptochrome 1 (Cry1), an essential clock component, displays evening-time expression and serves as a strong repressor at morning-time elements (E box/E' box).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21236481", "endSection": "sections.0" }, { "offsetInBeginSection": 713, "offsetInEndSection": 1037, "text": "A genetic complementation assay in Cry1(-/-):Cry2(-/-) cells revealed that substantial delay of Cry1 expression is required to restore circadian rhythmicity, and its prolonged delay slows circadian oscillation. Taken together, our data suggest that phase delay in Cry1 transcription is required for mammalian clock function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21236481", "endSection": "sections.0" }, { "offsetInBeginSection": 635, "offsetInEndSection": 1123, "text": "the 24-h mRNA rhythms of the following genes were suppressed in db/db mice compared with control mice: the clock genes period homolog 1/2 (Per1/2) and cryptochrome 1/2 (Cry1/2) and their target genes D site albumin promoter-binding protein (Dbp) and peroxisome proliferator-activated receptor-\u03b3 (Pparg) in the aorta and mesenteric arteries; Dbp in the heart; Per1, nuclear receptor subfamily 1, group D, member 1 (Rev-erba), and Dbp in the kidney; and Per1 in the suprachiasmatic nucleus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22140039", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "In mammals, circadian rhythms in behavior and physiology are controlled by a central pacemaker, the SCN, and subordinated clocks throughout the body. On the molecular level, these clocks are based on transcriptional/translational feedback loops involving a set of clock genes that regulate their own transcription. Among the components driving the mammalian circadian clock are the Period 1 and 2 (Per1 and Per2) and Cryptochrome 1 and 2 (Cry1 and Cry2) genes. I", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16731656", "endSection": "sections.0" }, { "offsetInBeginSection": 611, "offsetInEndSection": 1380, "text": "The mammalian clock protein, cryptochrome 1 (CRY1), is degraded via the FBXL3-mediated ubiquitination pathway, suggesting that it is also likely to be targeted by the deubiquitination pathway. Here, we identified that USP2a, a circadian-controlled deubiquitinating enzyme, interacts with CRY1 and enhances its protein stability via deubiquitination upon serum shock. Depletion of Usp2a by shRNA greatly enhances the ubiquitination of CRY1 and dampens the oscillation amplitude of the CRY1 protein during a circadian cycle. By stabilizing the CRY1 protein, USP2a represses the Per2 promoter activity as well as the endogenous Per2 gene expression. We also demonstrated that USP2a-dependent deubiquitination and stabilization of the CRY1 protein occur in the mouse liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22669941", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "The mammalian circadian clock is composed of interlocking feedback loops. Cryptochrome is a central component in the core negative feedback loop, whereas Rev-Erb\u03b1, a member of the nuclear receptor family, is an essential component of the interlocking loop.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23471982", "endSection": "sections.0" }, { "offsetInBeginSection": 765, "offsetInEndSection": 1065, "text": "By analyzing the Fbxl3 and Cryptochrome 1 double-mutant mice, we found that FBXL3 also regulates the amplitudes of E-box-driven gene expression. These two separate roles of FBXL3 in circadian feedback loops provide a mechanism that contributes to the period determination and robustness of the clock.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23471982", "endSection": "sections.0" } ] }, { "body": "Describe July Effect.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20145785", "http://www.ncbi.nlm.nih.gov/pubmed/24152859", "http://www.ncbi.nlm.nih.gov/pubmed/23737378", "http://www.ncbi.nlm.nih.gov/pubmed/20512532", "http://www.ncbi.nlm.nih.gov/pubmed/24578770", "http://www.ncbi.nlm.nih.gov/pubmed/25374038", "http://www.ncbi.nlm.nih.gov/pubmed/25633735", "http://www.ncbi.nlm.nih.gov/pubmed/25542761", "http://www.ncbi.nlm.nih.gov/pubmed/24384663", "http://www.ncbi.nlm.nih.gov/pubmed/25860519", "http://www.ncbi.nlm.nih.gov/pubmed/24059450" ], "ideal_answer": [ "The July effect is the hypothetical increase in morbidity and mortality thought to be associated with the influx of new (or newly promoted) trainees during the first portion of the academic year (in July)." ], "type": "summary", "id": "56c1f00fef6e394741000040", "snippets": [ { "offsetInBeginSection": 325, "offsetInEndSection": 459, "text": "It is unclear, however, if this difference was related to climatological changes or inexperienced medical trainees (the July effect). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25860519", "endSection": "abstract" }, { "offsetInBeginSection": 2991, "offsetInEndSection": 3206, "text": " Given the nonteaching nature of these hospitals, the findings demonstrate that increases in the rate of SSI during the summer are more likely related to ecological and/or environmental factors than the July effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25860519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Lower quality of care and poorer outcomes are suspected when new trainees (eg, residents) start in July in teaching hospitals, the so-called \"the July effect.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25542761", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 178, "text": "The \"August\" or \"July effect\" describes increased errors and reduced patient safety during this transition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25633735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "PURPOSE: Researchers have found mixed results about the risk to patient safety in July, when newly minted physicians enter U.S. hospitals to begin their clinical training, the so-called \"July effect.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25374038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "INTRODUCTION: There has been concern of increased emergency department (ED) length of stay (LOS) during the months when new residents are orienting to their roles. This so-called \"July Effect\" has long been thought to increase LOS, and potentially contribute to hospital overcrowding and increased waiting time for patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24578770", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 363, "text": "SUMMARY OF BACKGROUND DATA: The July effect is the hypothetical increase in morbidity and mortality thought to be associated with the influx of new (or newly promoted) trainees during the first portion of the academic year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24384663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Studies of whether inpatient mortality in US teaching hospitals rises in July as a result of organizational disruption and relative inexperience of new physicians (July effect) find small and mixed results, perhaps because study populations primarily include low-risk inpatients whose mortality outcomes are unlikely to exhibit a July effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152859", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1513, "text": "Elderly hip fracture patients treated at teaching hospitals had 12% greater relative risk of mortality in July/August (ie, experience a \"July effect\") compared with nonteaching hospitals during that time period (1998-2003).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20145785", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 486, "text": "Many have suggested that these new medical residents may produce errors and worsen patient outcomes-the so-called \"July Effect;\" however, we have found no U.S. evidence documenting this effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20512532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "A "July effect" of increased complications when new trainees begin residency has been reported widely by the media.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23737378", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1493, "text": "The July Effect thus contributed to only a 2.4% higher FTOR in teaching hospitals compared to 19% in non teaching hospitals. The July Effect is reflective of an overall increase in morbidity in all hospitals at the beginning of the academic cycle and it had a pronounced effect in non-teaching hospitals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24059450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "Studies of whether inpatient mortality in US teaching hospitals rises in July as a result of organizational disruption and relative inexperience of new physicians (July effect) find small and mixed results, perhaps because study populations primarily include low-risk inpatients whose mortality outcomes are unlikely to exhibit a July effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152859", "endSection": "abstract" } ] }, { "body": "Which intermediate filament (IF) protein can be used as a non-specific marker of the neuronal precursor cells of the subventricular zone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21527990", "http://www.ncbi.nlm.nih.gov/pubmed/23131160", "http://www.ncbi.nlm.nih.gov/pubmed/20552272", "http://www.ncbi.nlm.nih.gov/pubmed/15458607", "http://www.ncbi.nlm.nih.gov/pubmed/16567040", "http://www.ncbi.nlm.nih.gov/pubmed/16647786", "http://www.ncbi.nlm.nih.gov/pubmed/17717696", "http://www.ncbi.nlm.nih.gov/pubmed/11294470", "http://www.ncbi.nlm.nih.gov/pubmed/22027098", "http://www.ncbi.nlm.nih.gov/pubmed/10802345", "http://www.ncbi.nlm.nih.gov/pubmed/15056462", "http://www.ncbi.nlm.nih.gov/pubmed/11078926", "http://www.ncbi.nlm.nih.gov/pubmed/23407958", "http://www.ncbi.nlm.nih.gov/pubmed/14715941", "http://www.ncbi.nlm.nih.gov/pubmed/12812760" ], "ideal_answer": [ "Nestin can be used as a nonspecific marker protein for precursor cells in the subventricular zone (SVZ). Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's SVZ." ], "exact_answer": [ "Nestin" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005882", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0021849" ], "type": "factoid", "id": "5540ca8a0083d1bf0e000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's subventricular zone (SVZ)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15056462", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 465, "text": "nestin, a marker protein for precursor cells in the subventricular zone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11078926", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 101, "text": "adult subventricular zone (SVZ) stem and progenitor cells express nestin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527990", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 646, "text": "the typical protein of neural progenitors, nestin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20552272", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 675, "text": "the nonspecific precursor cell marker Nestin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407958", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1130, "text": "In the subventricular zone, this effect was exerted selectively on a precursor subpopulation expressing nestin but not neuronal or glial cell-specific proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14715941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Nestin is an intermediate filament protein expressed in neuroepithelial stem cells during development and it is later replaced by cell specific neuronal or glial filaments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23131160", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 485, "text": "The results indicate that administration of thyroid hormone and retinoic acid increases the expression of Ki67, a nuclear antigen associated with cell proliferation, and of nestin, a marker protein for precursor cells in the subventricular zone of adult male rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11078926", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 668, "text": "Only a minority of stem cells expressed nestin, a marker for neural precursor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16647786", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 702, "text": "In addition, bone marrow transplantation promoted proliferation of ependymal and subependymal cells, identified by nestin (a neuroepithelial stem cell marker), within the ventricular zone and subventricular zone (VZ/SVZ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11294470", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 484, "text": "The results indicate that administration of thyroid hormone and retinoic acid increases the expression of Ki67, a nuclear antigen associated with cell proliferation, and of nestin, a marker protein for precursor cells in the subventricular zone of adult male rats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11078926", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 653, "text": "In all animals, 20-40% of the newly generated cells in the dentate gyrus and subventricular zone expressed the neural progenitor cell markers Musashi1 or Nestin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12812760", "endSection": "abstract" } ] }, { "body": "Which enzyme is involved in the maintenance of DNA (cytosine-5-)-methylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21268065", "http://www.ncbi.nlm.nih.gov/pubmed/19468253", "http://www.ncbi.nlm.nih.gov/pubmed/7638194", "http://www.ncbi.nlm.nih.gov/pubmed/20506537", "http://www.ncbi.nlm.nih.gov/pubmed/18536530", "http://www.ncbi.nlm.nih.gov/pubmed/17312023", "http://www.ncbi.nlm.nih.gov/pubmed/19789556", "http://www.ncbi.nlm.nih.gov/pubmed/22704242", "http://www.ncbi.nlm.nih.gov/pubmed/23393137", "http://www.ncbi.nlm.nih.gov/pubmed/19778587", "http://www.ncbi.nlm.nih.gov/pubmed/19923434", "http://www.ncbi.nlm.nih.gov/pubmed/19282482", "http://www.ncbi.nlm.nih.gov/pubmed/22072770", "http://www.ncbi.nlm.nih.gov/pubmed/18665914", "http://www.ncbi.nlm.nih.gov/pubmed/22967183", "http://www.ncbi.nlm.nih.gov/pubmed/15799776", "http://www.ncbi.nlm.nih.gov/pubmed/22761581", "http://www.ncbi.nlm.nih.gov/pubmed/22064703", "http://www.ncbi.nlm.nih.gov/pubmed/22278882", "http://www.ncbi.nlm.nih.gov/pubmed/20940144", "http://www.ncbi.nlm.nih.gov/pubmed/21559294", "http://www.ncbi.nlm.nih.gov/pubmed/18922972", "http://www.ncbi.nlm.nih.gov/pubmed/19417133", "http://www.ncbi.nlm.nih.gov/pubmed/18302924", "http://www.ncbi.nlm.nih.gov/pubmed/16963560", "http://www.ncbi.nlm.nih.gov/pubmed/17989773", "http://www.ncbi.nlm.nih.gov/pubmed/20007090", "http://www.ncbi.nlm.nih.gov/pubmed/22898819", "http://www.ncbi.nlm.nih.gov/pubmed/17965600", "http://www.ncbi.nlm.nih.gov/pubmed/22284370", "http://www.ncbi.nlm.nih.gov/pubmed/19825994", "http://www.ncbi.nlm.nih.gov/pubmed/19966177", "http://www.ncbi.nlm.nih.gov/pubmed/22934696", "http://www.ncbi.nlm.nih.gov/pubmed/20864525", "http://www.ncbi.nlm.nih.gov/pubmed/21625467", "http://www.ncbi.nlm.nih.gov/pubmed/23029374", "http://www.ncbi.nlm.nih.gov/pubmed/22633409", "http://www.ncbi.nlm.nih.gov/pubmed/20139415", "http://www.ncbi.nlm.nih.gov/pubmed/20364115", "http://www.ncbi.nlm.nih.gov/pubmed/16500889", "http://www.ncbi.nlm.nih.gov/pubmed/21553025", "http://www.ncbi.nlm.nih.gov/pubmed/20071334", "http://www.ncbi.nlm.nih.gov/pubmed/22323818", "http://www.ncbi.nlm.nih.gov/pubmed/22073356", "http://www.ncbi.nlm.nih.gov/pubmed/21389349", "http://www.ncbi.nlm.nih.gov/pubmed/22088914", "http://www.ncbi.nlm.nih.gov/pubmed/21163962", "http://www.ncbi.nlm.nih.gov/pubmed/17033890", "http://www.ncbi.nlm.nih.gov/pubmed/17576694", "http://www.ncbi.nlm.nih.gov/pubmed/21507353", "http://www.ncbi.nlm.nih.gov/pubmed/21913078", "http://www.ncbi.nlm.nih.gov/pubmed/16807237", "http://www.ncbi.nlm.nih.gov/pubmed/22538524", "http://www.ncbi.nlm.nih.gov/pubmed/21518897", "http://www.ncbi.nlm.nih.gov/pubmed/19932585", "http://www.ncbi.nlm.nih.gov/pubmed/18297739", "http://www.ncbi.nlm.nih.gov/pubmed/22048250", "http://www.ncbi.nlm.nih.gov/pubmed/20348135", "http://www.ncbi.nlm.nih.gov/pubmed/17929180", "http://www.ncbi.nlm.nih.gov/pubmed/19016755", "http://www.ncbi.nlm.nih.gov/pubmed/21532572", "http://www.ncbi.nlm.nih.gov/pubmed/19819843", "http://www.ncbi.nlm.nih.gov/pubmed/20820192", "http://www.ncbi.nlm.nih.gov/pubmed/19173286", "http://www.ncbi.nlm.nih.gov/pubmed/19450230", "http://www.ncbi.nlm.nih.gov/pubmed/22563479", "http://www.ncbi.nlm.nih.gov/pubmed/20035856", "http://www.ncbi.nlm.nih.gov/pubmed/22413869" ], "ideal_answer": [ "The mammalian DNA (cytosine-5) methyltransferase 1, DNMT1 is the major enzyme responsible for the maintenance of the DNA methylation patterns on the newly synthesized strand after DNA replication. DNMT1 prefers hemimethylated DNA and during DNA replication methylates hemimethylated CpG sites by copying methylation patterns from the parental DNA strand to the newly synthesized daughter strand. The equivalent of DNMT1 in plants is MET1." ], "exact_answer": [ "DNMT1", "MET1" ], "concepts": [ "http://www.uniprot.org/uniprot/CMT1_MAIZE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010216", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0090116", "http://www.uniprot.org/uniprot/DCM_ECOLI", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015257", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003886" ], "type": "factoid", "id": "51585b28d24251bc0500008d", "snippets": [ { "offsetInBeginSection": 969, "offsetInEndSection": 1198, "text": "his defect does not appear in mouse models with mutations in Dnmt3a and Mthfr genes and, therefore, it is specific for the Dnmt1 gene and is suggestive of a role of DNMT1 in imprint resetting or maintenance in the male germ line.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22967183", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633409", "endSection": "title" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1110, "text": "We obtained evidence that some 5-methylcytosine residues in these single-stranded DNAs can stimulate de novo methylation of adjacent sites by murine DNA 5-cytosine methyltransferase as effectively as 5-methylcytosine residues in double-stranded DNA stimulate maintenance methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7638194", "endSection": "sections.0" }, { "offsetInBeginSection": 249, "offsetInEndSection": 434, "text": "We present in vitro evidence that the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B, but not the maintenance enzyme DNMT1, are also redox-dependent DNA dehydroxymethylases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22898819", "endSection": "sections.0" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1035, "text": "Direct comparison to met1 plants, deficient in maintenance methyltransferase MET1, showed higher sensitivity of ddm1 plants to NaCl.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22538524", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "DNMT1, the major maintenance DNA methyltransferase in animals, helps to regulate gene expression, genome imprinting, and X-chromosome inactivation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22323818", "endSection": "sections.0" }, { "offsetInBeginSection": 634, "offsetInEndSection": 805, "text": "Correct establishment and maintenance of methylation patterns at imprinted genes has been associated with placental function and regulation of embryonic/fetal development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088914", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22072770", "endSection": "title" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1301, "text": "Thus, differential expression of CTCF and DNMT1 and -3B is not critical for maintenance of restricted latency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22072770", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Recent studies demonstrate that UHRF1 is required for DNA methylation maintenance by targeting DNMT1 to DNA replication foci, presumably through its unique hemi-methylated DNA-binding activity and interaction with DNMT1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22064703", "endSection": "sections.0" }, { "offsetInBeginSection": 134, "offsetInEndSection": 476, "text": "It is generally accepted that DNA methyltransferases carry out specific and non-overlapping functions, Dnmt3a and Dnmt3b being responsible for the establishment of methylation around the time of implantation and Dnmt1 ensuring that methylation is faithfully copied to daughter cells via what has come to be known as \"maintenance methylation.\"", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22048250", "endSection": "sections.0" }, { "offsetInBeginSection": 622, "offsetInEndSection": 768, "text": "A new model is emerging that takes into account a contribution of the de novo enzymes Dnmt3a and Dnmt3b in the maintenance of the DNA methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22048250", "endSection": "sections.0" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1270, "text": "We propose here observations in support of the hypothesis that the maintenance of methylation and subsequent silencing of a handful of germ line genes requires Dnmt3b but not Dnmt1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22048250", "endSection": "sections.0" }, { "offsetInBeginSection": 162, "offsetInEndSection": 407, "text": "DNA methyltransferase 1 (Dnmt1) is the enzyme responsible for maintaining the methylation marks through cell division. However, the de novo methyltransferases, Dnmt3a and Dnmt3b, can also contribute to the maintenance of the methylation pattern.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913078", "endSection": "sections.0" }, { "offsetInBeginSection": 569, "offsetInEndSection": 780, "text": "These new data support the notion that de novo DNMTs also have an important role in the maintenance of DNA methylation and suggest that, in addition to acting as oncogenes, they also behave as tumor suppressors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704242", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21518897", "endSection": "title" }, { "offsetInBeginSection": 103, "offsetInEndSection": 367, "text": "The DNA methyltransferase Dnmt1 is responsible for the propagation of methylation patterns to the next generation via its preferential methylation of hemimethylated CpG sites in the genome; however, how Dnmt1 maintains methylation patterns is not fully understood.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21518897", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21268065", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "In mammals Dnmt1 is the DNA methyltransferase chiefly responsible for maintaining genomic methylation patterns through DNA replication cycles, but how its maintenance activity is controlled is still not well understood.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21268065", "endSection": "sections.0" }, { "offsetInBeginSection": 706, "offsetInEndSection": 863, "text": "DMAP1 is a potent activator of DNMT1 methylation in vitro, suggesting that DMAP1 is a co-repressor that supports the maintenance and de novo action of DNMT1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20864525", "endSection": "sections.0" }, { "offsetInBeginSection": 173, "offsetInEndSection": 303, "text": "A group of enzymes, the DNA methyltransferases (DNMTs) tightly regulate both the initiation and maintenance of these methyl marks.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20364115", "endSection": "sections.0" }, { "offsetInBeginSection": 232, "offsetInEndSection": 408, "text": "Maintenance of DNA methylation depends on DNA methyltransferase 1 (Dnmt1) and intracellular S-adenosylmethionine (SAM) levels, and is inhibited by S-adenosylhomocysteine (SAH).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20035856", "endSection": "sections.0" }, { "offsetInBeginSection": 314, "offsetInEndSection": 416, "text": "While DNMT3a is mostly involved in de novo methylation, DNMT1 acts as a maintenance methyltransferase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19468253", "endSection": "sections.0" }, { "offsetInBeginSection": 252, "offsetInEndSection": 541, "text": "We propose a new model that suggests that the maintenance of DNA methylation relies not only on the recognition of hemimethylated DNA by DNA methyltransferase 1 (DNMT1) but also on the localization of the DNMT3A and DNMT3B enzymes to specific chromatin regions that contain methylated DNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19789556", "endSection": "sections.0" }, { "offsetInBeginSection": 130, "offsetInEndSection": 321, "text": "The maintenance methylase, DNMT1 (DNA methyltransferase 1), is a prominent enzyme in the process that is linked to DNA replication and drives the heritable nature of epigenetic modifications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450230", "endSection": "sections.0" }, { "offsetInBeginSection": 181, "offsetInEndSection": 341, "text": "We have shown previously that these drugs selectively and rapidly induce degradation of the maintenance DNA methyltransferase (DNMT) 1 by a proteasomal pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417133", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Inheritance of epigenetic information encoded by cytosine DNA methylation patterns is crucial for mammalian cell survival, in large part through the activity of the maintenance DNA methyltransferase (DNMT1).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19282482", "endSection": "sections.0" }, { "offsetInBeginSection": 295, "offsetInEndSection": 500, "text": "We and others have shown that DNA methyltransferase 1 (DNMT1), the maintenance methyltransferase, contributes to the cellular response to DNA damage, yet DNMT1's exact role in this process remains unclear.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20940144", "endSection": "sections.0" }, { "offsetInBeginSection": 301, "offsetInEndSection": 494, "text": "The maintenance function of Dnmt1 is regulated by its large regulatory N-terminal domain that interacts with other chromatin factors and is essential for the recognition of hemi-methylated DNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19173286", "endSection": "sections.0" }, { "offsetInBeginSection": 146, "offsetInEndSection": 380, "text": "In the absence of a human pituitary tumor cell line, small interfering RNA-mediated knockdown of the maintenance methyltransferase DNA methyltransferase (cytosine 5)-1 (Dnmt1) was used in the murine pituitary adenoma cell line AtT-20.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18922972", "endSection": "sections.0" }, { "offsetInBeginSection": 806, "offsetInEndSection": 962, "text": "We found that DNA methylation was maintained only when exogenous DNA methyltransferase 1 (DNMT1) and S-adenosyl methionine (SAM) were added to the reaction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19016755", "endSection": "sections.0" }, { "offsetInBeginSection": 357, "offsetInEndSection": 638, "text": "We examined the expression of DNMT1 and DNMT3a, representative of a maintenance and de novo methyltransferase respectively, in response to in-vitro depolarization of cortical neurons, using standard techniques such as high potassium (KCl) or the sodium channel agonist veratridine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18536530", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "DNA methyltransferase-1 (DNMT1) has a higher specific activity on hemimethylated DNA than on unmethylated DNA, but this preference is too small to explain the faithful mitotic inheritance of genomic methylation patterns. New genetic studies in plants and mammals have identified a novel factor that increases the fidelity of maintenance methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18302924", "endSection": "sections.0" }, { "offsetInBeginSection": 347, "offsetInEndSection": 520, "text": "Dnmt1 is the main maintenance methyltransferase in the mouse and its expression is regulated by a splicing mechanism that dictates the expression of stage-specific isoforms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18297739", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Phosphorylation of serine-515 activates the Mammalian maintenance methyltransferase Dnmt1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17965600", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "DNA methyltransferase 1 methylates hemi-methylated CG sites generated during DNA replication.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17965600", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) including the maintenance enzyme DNMT 1 and de novo methyltransferases DNMT 3a and DNMT 3b.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17929180", "endSection": "sections.0" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1327, "text": "Our data suggest that DNMT1 might be essential for maintenance of DNA methylation, proliferation, and survival of cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963560", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Maintenance DNA methyltransferase (Met1) and silencing of CpG-methylated foreign DNA in Volvox carteri.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17033890", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "DNA methylation plays an important role in the gene-silencing network of higher eukaryotes. We have analyzed the 21.5-kb maintenance methyltransferase (M-MTase) gene, met1, of the multicellular green alga Volvox carteri.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17033890", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "DNA damage-induced down-regulation of human Cdc25C and Cdc2 is mediated by cooperation between p53 and maintenance DNA (cytosine-5) methyltransferase 1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16807237", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Methylation at the 5-position of DNA cytosine on the vertebrate genomes is accomplished by the combined catalytic actions of three DNA methyltransferases (DNMTs), the de novo enzymes DNMT3A and DNMT3B and the maintenance enzyme DNMT1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393137", "endSection": "sections.0" }, { "offsetInBeginSection": 433, "offsetInEndSection": 613, "text": "DNA methylation, the major form of epigenetic modifications, is catalyzed by the maintenance DNA methyltransferase (DNMT) 1 and/or the de novo methyltransferases DNMT3A and DNMT3B.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22934696", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The maintenance methylation of hemimethylated CpG sites by the DNA methyltransferase Dnmt1 is the molecular basis of the inheritance of DNA methylation patterns.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633409", "endSection": "sections.0" }, { "offsetInBeginSection": 309, "offsetInEndSection": 416, "text": "The allosteric site(s) on Dnmt1 can regulate processes of de novo and maintenance DNA methylation in cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21507353", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21389349", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21163962", "endSection": "sections.0" }, { "offsetInBeginSection": 169, "offsetInEndSection": 291, "text": "In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20820192", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "DNA methyltransferases (DNMTs) are essential for maintenance of aberrant methylation in cancer cells and play important roles in the development of cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20506537", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "DNA methyltransferase-1 (Dnmt1) is involved in the maintenance of DNA methylation patterns and is crucial for normal mammalian development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20007090", "endSection": "sections.0" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1109, "text": "DNMT1, which is important for maintenance of methylation, increased across development and stayed high in adult cortex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19966177", "endSection": "sections.0" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1296, "text": "Our results indicate that DNMT1 plays the main role in maintenance of methylation of CXCR4 promoter, while DNMT3B may function as an accessory DNA methyltransferase to modulate CXCR4 expression in AsPC1 cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19932585", "endSection": "sections.0" }, { "offsetInBeginSection": 110, "offsetInEndSection": 225, "text": "DNA methylation patterns are established and maintained by three DNA methyltransferases: DNMT1, DNMT3A, and DNMT3B.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19825994", "endSection": "sections.0" }, { "offsetInBeginSection": 285, "offsetInEndSection": 514, "text": "According to their structure and functions, DNA methyltransferases (Dnmts) are divided into two major families in mammalian cells: maintenance methyltransferase (Dnmt1) and de novo methyltransferases (Dnmt3a, Dnmt3b, and Dnmt3L).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19819843", "endSection": "sections.0" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1216, "text": "The 5-LOX DNA methylation increased with the age of the cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19778587", "endSection": "sections.0" } ] }, { "body": "Is transcapillary albumin escape altered in diabetic patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2060321", "http://www.ncbi.nlm.nih.gov/pubmed/21219847", "http://www.ncbi.nlm.nih.gov/pubmed/15616033", "http://www.ncbi.nlm.nih.gov/pubmed/2951101", "http://www.ncbi.nlm.nih.gov/pubmed/2949917", "http://www.ncbi.nlm.nih.gov/pubmed/3522326", "http://www.ncbi.nlm.nih.gov/pubmed/10922975", "http://www.ncbi.nlm.nih.gov/pubmed/7579054", "http://www.ncbi.nlm.nih.gov/pubmed/22950063", "http://www.ncbi.nlm.nih.gov/pubmed/6642091", "http://www.ncbi.nlm.nih.gov/pubmed/1619500", "http://www.ncbi.nlm.nih.gov/pubmed/18347777", "http://www.ncbi.nlm.nih.gov/pubmed/10703889", "http://www.ncbi.nlm.nih.gov/pubmed/3569694", "http://www.ncbi.nlm.nih.gov/pubmed/10027580", "http://www.ncbi.nlm.nih.gov/pubmed/2210073", "http://www.ncbi.nlm.nih.gov/pubmed/11395874", "http://www.ncbi.nlm.nih.gov/pubmed/8712223", "http://www.ncbi.nlm.nih.gov/pubmed/10405209", "http://www.ncbi.nlm.nih.gov/pubmed/2970919", "http://www.ncbi.nlm.nih.gov/pubmed/378740", "http://www.ncbi.nlm.nih.gov/pubmed/1547928", "http://www.ncbi.nlm.nih.gov/pubmed/9536925", "http://www.ncbi.nlm.nih.gov/pubmed/8960847", "http://www.ncbi.nlm.nih.gov/pubmed/22516624", "http://www.ncbi.nlm.nih.gov/pubmed/7698029", "http://www.ncbi.nlm.nih.gov/pubmed/8187356", "http://www.ncbi.nlm.nih.gov/pubmed/18712042", "http://www.ncbi.nlm.nih.gov/pubmed/8436254", "http://www.ncbi.nlm.nih.gov/pubmed/15581746", "http://www.ncbi.nlm.nih.gov/pubmed/15019550" ], "ideal_answer": [ "An altered TERalb is present in type 2 diabetic patients, both with normal and altered patterns of AER.\nTERalb is increased also in normo-albuminuric type 1 diabetic patients." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012709", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000418", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003929" ], "type": "yesno", "id": "5321b4959b2d7acc7e000007", "snippets": [ { "offsetInBeginSection": 1646, "offsetInEndSection": 1826, "text": "On the contrary, altered TERalb and increased carotid artery intimal thickness are shown by all hypertensive type 2 diabetic patients, both with normal and altered patterns of AER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15616033", "endSection": "abstract" }, { "offsetInBeginSection": 1686, "offsetInEndSection": 1804, "text": "Altered systemic capillary permeability characterizes insulin-resistant hypertensive patients with Metabolic Syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15019550", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1673, "text": "TERalb is increased in normo-albuminuric type 1 diabetic patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10703889", "endSection": "abstract" } ] }, { "body": "Which genes does thyroid hormone receptor beta1 regulate in the liver?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19324998", "http://www.ncbi.nlm.nih.gov/pubmed/9224811", "http://www.ncbi.nlm.nih.gov/pubmed/9832432", "http://www.ncbi.nlm.nih.gov/pubmed/19916081", "http://www.ncbi.nlm.nih.gov/pubmed/10319950" ], "ideal_answer": [ "LDL receptor\"//\n\"ChREBP\"//\n\"ME\", \"malic enzyme\"//\n\"cytochrome P450 oxidoreductase\"//" ], "exact_answer": [ [ "LDL receptor" ], [ "ChREBP", "Carbohydrate response element binding protein" ], [ "ME", "malic enzyme" ], [ "cytochrome P450 oxidoreductase" ] ], "concepts": [ "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.uniprot.org/uniprot/THBB_XENLA", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.uniprot.org/uniprot/THB_MOUSE", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ], "type": "list", "id": "516c0ebc298dcd4e5100006e", "snippets": [ { "offsetInBeginSection": 1473, "offsetInEndSection": 1629, "text": "our data suggests that TRbeta1-mediated down regulation of hepatic LDLr gene may play a critical role in iodine excess-induced hypercholesterolemic effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19916081", "endSection": "sections.0" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1449, "text": "These data suggest that ChREBP mRNA expression is positively regulated by TR-beta1 and TH at the transcriptional level in mammals. This novel observation indicates that TH fine-tunes hepatic lipogenesis via regulating SREBP-1c and ChREBP gene expression reciprocally.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324998", "endSection": "sections.0" }, { "offsetInBeginSection": 1842, "offsetInEndSection": 2247, "text": "In contrast treatment with L-T3 produced an increase in S14 and ME but no change in TR beta-/- mice. From these results, it can be concluded that regulation of HR and EE are independent of TR beta. With the exception of serum cholesterol concentration and liver ME mRNA accumulation, all other markers of TH action examined during TH deprivation exhibited the expected responses in the absence of TR beta.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9832432", "endSection": "sections.0" }, { "offsetInBeginSection": 773, "offsetInEndSection": 1032, "text": "However, the T3-activated expression of the GH gene in GH3-PV and ME gene in SK-Hep-1-PV was repressed by approximately 30% and 90%, respectively, indicating the lack of correlation of PV/TRpbeta1 protein ratio with the dominant negative potency of mutant PV.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10319950", "endSection": "sections.0" }, { "offsetInBeginSection": 656, "offsetInEndSection": 944, "text": "Transient cotransfection of P450R promoter/chloramphenicol acetyl transferase (CAT) constructs and the thyroid hormone receptor beta1 (TR beta1) expression plasmid into rat hepatoma H4IIE cells resulted in a 2.4-fold induction of promoter activity that was both T3 and TR beta1 dependent.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9224811", "endSection": "sections.0" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1173, "text": "At the molecular level, we detected a dose-dependent attenuation of hepatic low density lipoprotein receptor (LDLr) and thyroid hormone receptor beta1 (TRbeta1) expression in parallel to the change of serum cholesterol.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19916081", "endSection": "sections.0" } ] }, { "body": "Are conserved noncoding elements associated with developmental genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "http://www.ncbi.nlm.nih.gov/pubmed/16630819", "http://www.ncbi.nlm.nih.gov/pubmed/16859531", "http://www.ncbi.nlm.nih.gov/pubmed/19562753", "http://www.ncbi.nlm.nih.gov/pubmed/21175683", "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "http://www.ncbi.nlm.nih.gov/pubmed/19698106", "http://www.ncbi.nlm.nih.gov/pubmed/19073165" ], "ideal_answer": [ "Yes. Numerous studies suggest that conserved noncoding elements span developmental regulatory genes and define regulatory domains." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051094", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048589", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050437", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050793", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032502" ], "type": "yesno", "id": "553d02c1f321868558000012", "snippets": [ { "offsetInBeginSection": 143, "offsetInEndSection": 345, "text": "Some characteristics of CNEs include their high frequency in mammalian genomes, their potential regulatory role in gene expression, and their enrichment in gene deserts nearby master developmental genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175683", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 786, "text": "we review recent findings that disruptions of CNEs, within or at long distance from the coding sequences of key genes involved in NCC development, result in neurocristopathies via the alteration of tissue- or stage-specific long-distance regulation of gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19698106", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1609, "text": "Analysis of CNEs, at least some of which are candidate regulatory elements, suggests that ancestral CNEs partitioned between gene duplicates. These results help explain the evolutionary pathways by which the developmentally important family of FgfD molecules arose and the deduced principles that guided FgfD evolution are likely applicable to the evolution of developmental regulation in many vertebrate multigene families", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19562753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 676, "text": "Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control. On the loci of two developmental transcription factor genes, SOX3 and PAX6, we demonstrate that HCNEs conserved between human and zebrafish can be systematically and reliably tested for their regulatory function in multiple stable transgenes in zebrafish, and their genomic reach estimated with confidence using synteny conservation and HCNE density along these loci. HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 875, "text": "We show that human HCNEs result in expression patterns in zebrafish equivalent to those in mouse, establishing zebrafish as a suitable model for large-scale testing of human developmental enhancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1390, "text": "HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Organization of conserved elements near key developmental regulators in vertebrate genomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "endSection": "title" }, { "offsetInBeginSection": 480, "offsetInEndSection": 647, "text": "Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16630819", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 353, "text": "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 645, "text": "Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16630819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Disruption of long-distance highly conserved noncoding elements in neurocristopathies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175683", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 422, "text": "Despite this, attempts at unearthing genome-wide regulatory elements conserved throughout the vertebrate lineage using BLAST-like approaches have thus far detected noncoding conservation in only a few hundred genes, mostly associated with regulation of transcription and development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859531", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 648, "text": "Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 354, "text": "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Organization of conserved elements near key developmental regulators in vertebrate genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "abstract" } ] }, { "body": "In what proportion of children with heart failure has Enalapril been shown to be safe and effective?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1318542", "http://www.ncbi.nlm.nih.gov/pubmed/23124387", "http://www.ncbi.nlm.nih.gov/pubmed/8110005", "http://www.ncbi.nlm.nih.gov/pubmed/12530495", "http://www.ncbi.nlm.nih.gov/pubmed/9315539", "http://www.ncbi.nlm.nih.gov/pubmed/7576410", "http://www.ncbi.nlm.nih.gov/pubmed/8512763", "http://www.ncbi.nlm.nih.gov/pubmed/14990637", "http://www.ncbi.nlm.nih.gov/pubmed/9381720", "http://www.ncbi.nlm.nih.gov/pubmed/12454107" ], "ideal_answer": [ "In children with heart failure evidence of the effect of enalapril is empirical. Enalapril was clinically safe and effective in 50% to 80% of for children with cardiac failure secondary to congenital heart malformations before and after cardiac surgery, impaired ventricular function , valvar regurgitation, congestive cardiomyopathy, , arterial hypertension, life-threatening arrhythmias coexisting with circulatory insufficiency. \nACE inhibitors have shown a transient beneficial effect on heart failure due to anticancer drugs and possibly a beneficial effect in muscular dystrophy-associated cardiomyopathy, which deserves further studies." ], "exact_answer": [ "50% to 80%" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015773", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://www.biosemantics.org/jochem#4249241", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054144", "http://www.biosemantics.org/jochem#4175579", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143", "http://www.biosemantics.org/jochem#4250224", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004656", "http://www.disease-ontology.org/api/metadata/DOID:9651", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.disease-ontology.org/api/metadata/DOID:9775", "http://www.biosemantics.org/jochem#4176194", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002648" ], "type": "factoid", "id": "515dd3d5298dcd4e5100001c", "snippets": [ { "offsetInBeginSection": 1407, "offsetInEndSection": 1609, "text": "The responses to IV KCl were attenuated by concomitant furosemide (p\u00a0=\u00a00.01), amphotericin B (p\u00a0<\u00a00.01), and KCl in parenteral nutrition (p\u00a0<\u00a00.01). The responses were augmented by concomitant enalapril", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124387", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 306, "text": "To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14990637", "endSection": "sections.0" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1441, "text": "Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14990637", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Patients with intraatrial baffle procedure for transposition of the great arteries (TGA) have diastolic dysfunction, decreased exercise capacity, stroke volume response and elevated systemic vascular resistance (SVR) during exercise.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12530495", "endSection": "sections.0" }, { "offsetInBeginSection": 1713, "offsetInEndSection": 1887, "text": "We conclude that short-term (<1 year) use of enalapril does not improve exercise performance in patients with TGA in whom the intraatrial baffle procedure has been performed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12530495", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 428, "text": "A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12454107", "endSection": "sections.0" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1676, "text": "In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12454107", "endSection": "sections.0" }, { "offsetInBeginSection": 208, "offsetInEndSection": 417, "text": "Patients who have undergone the Fontan procedure have decreased cardiac output, increased systemic vascular resistance, abnormal diastolic function, and decreased exercise capacity compared with normal people.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9315539", "endSection": "sections.0" }, { "offsetInBeginSection": 1884, "offsetInEndSection": 2107, "text": "We conclude that enalapril administration for 10 weeks does not alter abnormal systemic vascular resistance, resting cardiac index, diastolic function, or exercise capacity in patients who have undergone a Fontan procedure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9315539", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 642, "text": "Angiotensin convertase inhibitor (Enalapril) was used in 51 children aged 4 days up to 18 years (mean 4.3 +/- 5.5, years). As many as 27 subjects were newborns (4) and infants (23). The patients suffered from circulatory insufficiency due to congestive cardiomyopathy (13 cases). 6 treated subjects suffered from circulatory insufficiency due to congenital heart malformations before cardiac surgery and 22 after it (including complex malformations operated according to Fontan method). 10 children were treated because of arterial hypertension. 4 subjects suffered form life-threatening arrhythmias coexisting with circulatory insufficiency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9381720", "endSection": "sections.0" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1233, "text": "4 patients (8%) died during treatment but their deaths can not be related to angiotensin convertase inhibitor therapy. In the other children (82%) the beneficial influence of angiotensin convertase inhibitor use was found (improvement in comparison with the state before convertase inhibitor introduction). In 10% of subjects enalapril did not show any significant therapeutic effect", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9381720", "endSection": "sections.0" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1385, "text": "We conclude that the combination of ACE inhibitor and beta-blocker deserves further exploration for inclusion in any management regimen for the treatment of muscular dystrophy-associated cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7576410", "endSection": "sections.0" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1182, "text": "Addition of these medications, never before attempted in the management of cardiomyopathy associated with generalized myopathic disease, complemented each other in relieving symptoms and reversing signs of congestive heart failure and DCM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7576410", "endSection": "sections.0" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1098, "text": "Enalapril was clinically safe and effective for children with cardiac failure secondary to ventricular impairment, valvar regurgitation, or after cardiac surgery. Renal failure was a problem in young infants with left-to-right shunts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8110005", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 694, "text": "In a tertiary referral centre 63 patients underwent 67 treatment periods with enalapril. The median age was 5.4 months. All children had signs of heart failure: congestive cardiac failure with breathlessness at rest was present in 88%. Haemodynamic groups were left-to-right shunt (n = 15), impaired ventricular function (n = 14), after cardiac surgery (n = 23), valvar regurgitation (n = 12), and hypertension (n = 3). Serial clinical, radiological, and laboratory data were used to judge outcome. The mean (SD) maximal dose was 0.30 (0.21) mg/kg/day. Thirty nine (58%) patients improved, 20 (30%) showed no improvement, and eight (12%) had side effects requiring discontinuation of enalapril.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8110005", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "We studied the inhibition of angiotensin converting enzyme (ACE) in eight infants with congestive heart failure (CHF) poorly controlled with digoxin and diuretics, treated orally with 0.25 mg kg-1 enalapril maleate once a day", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8512763", "endSection": "sections.0" }, { "offsetInBeginSection": 584, "offsetInEndSection": 680, "text": "In infants with CHF, mean baseline ACE activity was significantly higher than in control infants", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8512763", "endSection": "sections.0" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1397, "text": "Converting enzyme inhibitors may benefit \"heart failure\" associated with large ventricular septal defects and normal or mildly elevated pulmonary resistance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1318542", "endSection": "sections.0" } ] }, { "body": "Is myasthenia gravis associated with osteoporosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15168159", "http://www.ncbi.nlm.nih.gov/pubmed/25122205", "http://www.ncbi.nlm.nih.gov/pubmed/25285145", "http://www.ncbi.nlm.nih.gov/pubmed/22531999", "http://www.ncbi.nlm.nih.gov/pubmed/23543381", "http://www.ncbi.nlm.nih.gov/pubmed/22840813", "http://www.ncbi.nlm.nih.gov/pubmed/15003307", "http://www.ncbi.nlm.nih.gov/pubmed/11328209", "http://www.ncbi.nlm.nih.gov/pubmed/24935165", "http://www.ncbi.nlm.nih.gov/pubmed/2237235", "http://www.ncbi.nlm.nih.gov/pubmed/16690366" ], "ideal_answer": [ "Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased risk of glucocorticoid-induced osteoporosis. Thymectomy can also increase risk for osteoporosis. Appropriate osteoporosis preventive measures can reduce osteoporosis risk in MG patients." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:437", "http://www.disease-ontology.org/api/metadata/DOID:11476" ], "type": "yesno", "id": "55032d8be9bde69634000033", "snippets": [ { "offsetInBeginSection": 508, "offsetInEndSection": 615, "text": "We performed PVP in 4 patients with generalized MG associated with recent steroid-induced symptomatic VFs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543381", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 436, "text": "In this case report, we used tacrolimus to successfully treat a 13-year-old boy with ocular MG who had suffered from severe steroid complications, including a failure of thrive and osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22840813", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 573, "text": " INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531999", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1462, "text": "RESULTS: Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84-1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67-1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31-3.14]) compared with MG patients without glucocorticoid exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531999", "endSection": "abstract" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1405, "text": "The RANKL/OPG ratio and indices of bone metabolisms are also not affected by THX, although THX increases the levels of IL-7 and RANKL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690366", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 575, "text": "Both disorders had been controlled for around 15 years by oral prednisolone and a cholinesterase inhibitor following surgical removal of invasive thymoma and radiotherapy, but muscular weakness due to myalgia and an increase in serum levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared immediately after cessation of these drugs, which was done because the patient had multiple bone fractures and severe osteoporosis due to the long-term corticosteroid therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15168159", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 391, "text": "We measured bone density in 36 patients (26 females and 10 males) who had undergone long-term prednisolone administration, and found a decrease in bone density in 31% of female patients and osteoporosis in only 11.5% (three cases).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15003307", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 681, "text": "In conclusion, prednisolone-treated patients with myasthenia gravis have an acceptable risk of bone loss if prophylactic medication is administered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15003307", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 572, "text": "INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531999", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1020, "text": "Alendronate should be used with caution in patients with myasthenia gravis who have corticosteroid-induced osteoporosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24935165", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 614, "text": "In this paper we present two cases of young women who developed severe PAO with vertebral fractures: a 42-year-old woman with a family history of osteoporosis, and a 21-year-old woman affected with myasthenia gravis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25285145", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 549, "text": "Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531999", "endSection": "abstract" } ] }, { "body": "Which cell type has the protein Chromogranin A as marker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25532001", "http://www.ncbi.nlm.nih.gov/pubmed/25294372", "http://www.ncbi.nlm.nih.gov/pubmed/25294889", "http://www.ncbi.nlm.nih.gov/pubmed/25394660", "http://www.ncbi.nlm.nih.gov/pubmed/24888775", "http://www.ncbi.nlm.nih.gov/pubmed/24897131", "http://www.ncbi.nlm.nih.gov/pubmed/25177680", "http://www.ncbi.nlm.nih.gov/pubmed/25099181", "http://www.ncbi.nlm.nih.gov/pubmed/25220535", "http://www.ncbi.nlm.nih.gov/pubmed/25501094" ], "triples": [ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/P33716", "o": "true" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503333373136007", "o": "Chromogranin-A" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P33716", "o": "http://linkedlifedata.com/resource/#_503333373136007" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/P33716", "o": "http://purl.uniprot.org/keywords/964" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/964", "o": "Secreted" } ], "ideal_answer": [ "Chromogranin A is a marker for neuroendocrine cells" ], "exact_answer": [ "neuroendocrine cells" ], "concepts": [ "http://www.uniprot.org/uniprot/CMGA_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000943", "http://www.biosemantics.org/jochem#4266983", "http://www.biosemantics.org/jochem#4262122", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053379", "http://www.biosemantics.org/jochem#4218257", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002864", "http://www.uniprot.org/uniprot/CMGA_HUMAN" ], "type": "factoid", "id": "54e262daae9738404b000018", "snippets": [ { "offsetInBeginSection": 562, "offsetInEndSection": 642, "text": "Neuroendocrine differentiation (chromogranin A and/or synaptophysin positivity) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294889", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1093, "text": "All paragangliomas were universally positive for chromogranin A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294372", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 92, "text": "chromogranin A (CGA) is a useful marker for pancreatic neuroendocrine tumors (pNET)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25220535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Together with Chromogranin B and Secretogranins, Chromogranin A (CGA) is stored in secretory (chromaffin) granules of the diffuse neuroendocrine system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25177680", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 168, "text": "Chromogranin A (CgA) is the most important general tumour marker used in the diagnosis and follow-up of patients with neuroendocrine tumours (NET).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25532001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Chromogranin A (CgA) not only plays an important role in pathologic diagnosis, but is also used as a circulating biomarker in patients with gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501094", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1274, "text": "numbers of chromogranin A (CHGA)-positive enteroendocrine cells (EEC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25394660", "endSection": "abstract" }, { "offsetInBeginSection": 1761, "offsetInEndSection": 1816, "text": " CgA is a reliable serum diagnostic biomarker for PNETs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25099181", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 186, "text": "Chromogranin A (CgA) was considered as the most practical and useful serum tumor marker in PNET patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25099181", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 461, "text": "the neuroendocrine markers chromogranin A and synaptophysin;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24888775", "endSection": "abstract" } ] }, { "body": "Does a selective sweep increase genetic variation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17396267", "http://www.ncbi.nlm.nih.gov/pubmed/16367838", "http://www.ncbi.nlm.nih.gov/pubmed/21624997", "http://www.ncbi.nlm.nih.gov/pubmed/21076829", "http://www.ncbi.nlm.nih.gov/pubmed/16951057", "http://www.ncbi.nlm.nih.gov/pubmed/20352120", "http://www.ncbi.nlm.nih.gov/pubmed/22087274", "http://www.ncbi.nlm.nih.gov/pubmed/24075201", "http://www.ncbi.nlm.nih.gov/pubmed/16322515", "http://www.ncbi.nlm.nih.gov/pubmed/24465214", "http://www.ncbi.nlm.nih.gov/pubmed/24126360", "http://www.ncbi.nlm.nih.gov/pubmed/21705748", "http://www.ncbi.nlm.nih.gov/pubmed/20140188", "http://www.ncbi.nlm.nih.gov/pubmed/22491190", "http://www.ncbi.nlm.nih.gov/pubmed/21385389", "http://www.ncbi.nlm.nih.gov/pubmed/20978039", "http://www.ncbi.nlm.nih.gov/pubmed/18346126", "http://www.ncbi.nlm.nih.gov/pubmed/16339379", "http://www.ncbi.nlm.nih.gov/pubmed/24282552" ], "ideal_answer": [ "Selective sweep is a phenomenon in which the fixation of strongly beneficial alleles within a population reduces genetic diversity at partially linked neutral loci. Reduced variation or deviations from neutrality, along with an excess of fixed replacement sites, are indicative of selective sweep." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012641", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014644" ], "type": "yesno", "id": "5540a8d20083d1bf0e000001", "snippets": [ { "offsetInBeginSection": 1110, "offsetInEndSection": 1417, "text": "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282552", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1404, "text": "a selective sweep that has removed genetic variation from much of the drive X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22087274", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 853, "text": "evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21624997", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 624, "text": "recent independent selective sweeps in AGO2 have reduced genetic variation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978039", "endSection": "abstract" }, { "offsetInBeginSection": 1300, "offsetInEndSection": 1477, "text": "episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20352120", "endSection": "abstract" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1301, "text": "reduced variation or deviations from neutrality that might indicate a recent selective sweep", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17396267", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 732, "text": "a local selective sweep or demographic process that reduced variability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951057", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 257, "text": "reduced variation (a selective sweep)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339379", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1252, "text": "the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16367838", "endSection": "abstract" }, { "offsetInBeginSection": 1741, "offsetInEndSection": 2009, "text": "Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21705748", "endSection": "abstract" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1512, "text": "Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24126360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 481, "text": "In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075201", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1608, "text": "CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21385389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A selective sweep describes the reduction of linked genetic variation due to strong positive selection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21076829", "endSection": "abstract" } ] }, { "body": "Which disease phenotypes are associated to PRPS1 mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "http://www.ncbi.nlm.nih.gov/pubmed/23190330", "http://www.ncbi.nlm.nih.gov/pubmed/20380929", "http://www.ncbi.nlm.nih.gov/pubmed/24961627", "http://www.ncbi.nlm.nih.gov/pubmed/24285972" ], "ideal_answer": [ "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1." ], "exact_answer": [ [ "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5)" ], [ "Arts syndrome" ], [ "Non-syndromic sensorineural deafness (DFN2)" ] ], "type": "list", "id": "5713b0a51174fb175500000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 272, "text": "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1364, "text": "Our findings demonstrate that CMTX5, Arts syndrome and DFN2 are phenotypic clusters on an intrafamilial continuum, including overlapping phenotypes even within individuals. The respective phenotypic presentation seems to be determined by the exact PRPS1 mutation and the residual enzyme activity, the latter being largely influenced by the degree of skewed X-inactivation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 491, "text": "Mutations in PRPS1 are associated with a spectrum of non-syndromic to syndromic hearing loss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190330", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1085, "text": "Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "endSection": "title" }, { "offsetInBeginSection": 718, "offsetInEndSection": 995, "text": "Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20380929", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 720, "text": "Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20380929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285972", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1047, "text": "Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190330", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 271, "text": "The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24961627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "endSection": "title" } ] }, { "body": "Is indicated the use of antioxidant supplements in patients at risk for coronary artery disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19774218", "http://www.ncbi.nlm.nih.gov/pubmed/10575394", "http://www.ncbi.nlm.nih.gov/pubmed/8164066", "http://www.ncbi.nlm.nih.gov/pubmed/8650957", "http://www.ncbi.nlm.nih.gov/pubmed/23877741", "http://www.ncbi.nlm.nih.gov/pubmed/11944023", "http://www.ncbi.nlm.nih.gov/pubmed/9430400", "http://www.ncbi.nlm.nih.gov/pubmed/10329064", "http://www.ncbi.nlm.nih.gov/pubmed/12069675", "http://www.ncbi.nlm.nih.gov/pubmed/9877124", "http://www.ncbi.nlm.nih.gov/pubmed/18277182", "http://www.ncbi.nlm.nih.gov/pubmed/22342390", "http://www.ncbi.nlm.nih.gov/pubmed/7695869", "http://www.ncbi.nlm.nih.gov/pubmed/10987596", "http://www.ncbi.nlm.nih.gov/pubmed/9193380", "http://www.ncbi.nlm.nih.gov/pubmed/8472392", "http://www.ncbi.nlm.nih.gov/pubmed/9746269", "http://www.ncbi.nlm.nih.gov/pubmed/9723625", "http://www.ncbi.nlm.nih.gov/pubmed/9849356", "http://www.ncbi.nlm.nih.gov/pubmed/10077397", "http://www.ncbi.nlm.nih.gov/pubmed/22645453", "http://www.ncbi.nlm.nih.gov/pubmed/22293859", "http://www.ncbi.nlm.nih.gov/pubmed/15531665", "http://www.ncbi.nlm.nih.gov/pubmed/8479464", "http://www.ncbi.nlm.nih.gov/pubmed/18548846", "http://www.ncbi.nlm.nih.gov/pubmed/15567903", "http://www.ncbi.nlm.nih.gov/pubmed/15302616", "http://www.ncbi.nlm.nih.gov/pubmed/8602181", "http://www.ncbi.nlm.nih.gov/pubmed/11192356", "http://www.ncbi.nlm.nih.gov/pubmed/9659191", "http://www.ncbi.nlm.nih.gov/pubmed/10386507", "http://www.ncbi.nlm.nih.gov/pubmed/7977015", "http://www.ncbi.nlm.nih.gov/pubmed/8479463", "http://www.ncbi.nlm.nih.gov/pubmed/12204790", "http://www.ncbi.nlm.nih.gov/pubmed/18377792", "http://www.ncbi.nlm.nih.gov/pubmed/12090883", "http://www.ncbi.nlm.nih.gov/pubmed/23335472", "http://www.ncbi.nlm.nih.gov/pubmed/19033020", "http://www.ncbi.nlm.nih.gov/pubmed/10711786", "http://www.ncbi.nlm.nih.gov/pubmed/8946266", "http://www.ncbi.nlm.nih.gov/pubmed/16603825", "http://www.ncbi.nlm.nih.gov/pubmed/15153272", "http://www.ncbi.nlm.nih.gov/pubmed/11089430", "http://www.ncbi.nlm.nih.gov/pubmed/12741415", "http://www.ncbi.nlm.nih.gov/pubmed/12968298", "http://www.ncbi.nlm.nih.gov/pubmed/12732794", "http://www.ncbi.nlm.nih.gov/pubmed/22254063", "http://www.ncbi.nlm.nih.gov/pubmed/20400494", "http://www.ncbi.nlm.nih.gov/pubmed/20350251", "http://www.ncbi.nlm.nih.gov/pubmed/10656300", "http://www.ncbi.nlm.nih.gov/pubmed/9164706", "http://www.ncbi.nlm.nih.gov/pubmed/19859067", "http://www.ncbi.nlm.nih.gov/pubmed/24489984", "http://www.ncbi.nlm.nih.gov/pubmed/15117174", "http://www.ncbi.nlm.nih.gov/pubmed/23055813", "http://www.ncbi.nlm.nih.gov/pubmed/12675072", "http://www.ncbi.nlm.nih.gov/pubmed/15585762", "http://www.ncbi.nlm.nih.gov/pubmed/17275460", "http://www.ncbi.nlm.nih.gov/pubmed/10812586", "http://www.ncbi.nlm.nih.gov/pubmed/23833580", "http://www.ncbi.nlm.nih.gov/pubmed/21996047", "http://www.ncbi.nlm.nih.gov/pubmed/12492632", "http://www.ncbi.nlm.nih.gov/pubmed/18460663", "http://www.ncbi.nlm.nih.gov/pubmed/10498115", "http://www.ncbi.nlm.nih.gov/pubmed/8570438", "http://www.ncbi.nlm.nih.gov/pubmed/10696633", "http://www.ncbi.nlm.nih.gov/pubmed/10639540", "http://www.ncbi.nlm.nih.gov/pubmed/10600089", "http://www.ncbi.nlm.nih.gov/pubmed/11702901", "http://www.ncbi.nlm.nih.gov/pubmed/23022248", "http://www.ncbi.nlm.nih.gov/pubmed/21115589", "http://www.ncbi.nlm.nih.gov/pubmed/15693087" ], "ideal_answer": [ "antioxidant supplementation \nHowever there are no clear evidencies on the clinical and prognostic benefit of this supplementation. \nCurrently there areno recommendation for the antioxidant therapy in patients with coronary artery disease.\nCurrently the American Heart Association recommends consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but does not recommend antioxidant supplementation for the general population." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000975", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054059", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023921", "http://www.disease-ontology.org/api/metadata/DOID:4248", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003327", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010361", "http://www.disease-ontology.org/api/metadata/DOID:3393", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019587" ], "type": "yesno", "id": "53329c84d6d3ac6a34000040", "snippets": [ { "offsetInBeginSection": 157, "offsetInEndSection": 331, "text": "We and others have published observational epidemiologic studies in support of vitamins in the primary prevention of CVD, but the results from intervention studies are mixed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18377792", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 1053, "text": "For vitamin E, observational data suggest benefit at doses of 100 to 400 IU/d. Results from recent large-scale trials are mixed, with some showing modest benefit but others suggesting no benefit, especially for secondary prevention. Results for B vitamins are also mixed and further complicated by the recent folate fortification of the flour supply. If greater B vitamin intake does reduce CVD, the benefits are likely to be greatest for primary prevention and in populations with intake below dietary reference standards. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18377792", "endSection": "abstract" }, { "offsetInBeginSection": 1445, "offsetInEndSection": 1911, "text": "In the dose-response meta-analysis, each 30 mg/day increase in vitamin C, 30 IU/day increase in vitamin E, and 1 mg/day increase in beta-carotene yielded the estimated overall relative risk for CHD of 1.01 (95% CI, 0.99-1.02), 0.96 (95% CI, 0.94-0.99), and 1.00 (95% CI, 0.88-1.14), respectively. CONCLUSIONS: Our findings in this meta-analysis suggest that an increase in dietary intake of antioxidant vitamins has encouraging prospects for possible CHD prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18277182", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1514, "text": "High levels of \u03b1-tocopherol in serum were associated with 30% lower CAD risk in another study (HR 0.71; 95%CI 0.53-0.94). Among minerals (zinc, selenium, and chromium), an inverse association between zinc and CAD was observed; levels lower than 14.1 \u00b5mol/L were associated with an increased risk for CAD (RR 1.70; 95%CI 1.21-2.38).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877741", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1711, "text": "The information available on this issue is scarce. Further prospective studies are needed to elucidate the role of these nutrients in the cardiovascular risk of patients with diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877741", "endSection": "abstract" }, { "offsetInBeginSection": 1523, "offsetInEndSection": 1644, "text": "Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22342390", "endSection": "abstract" }, { "offsetInBeginSection": 1973, "offsetInEndSection": 2237, "text": " Coenzyme Q10 supplements at a dose of 150 mg can decrease oxidative stress and increase antioxidant enzyme activity in patients with CAD. A higher dose of coenzyme Q10 supplements (>150 mg/d) might promote rapid and sustainable antioxidation in patients with CAD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21996047", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1412, "text": "Alpha-tocopherol or beta-carotene supplementation has no protective effect on macrovascular outcomes or total mortality of diabetic male smokers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20350251", "endSection": "abstract" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1769, "text": "Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19033020", "endSection": "abstract" }, { "offsetInBeginSection": 2236, "offsetInEndSection": 2474, "text": "After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18460663", "endSection": "abstract" }, { "offsetInBeginSection": 1627, "offsetInEndSection": 1885, "text": " In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17275460", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1572, "text": " In this large cohort of apparently healthy US male physicians, self-selected supplementation with vitamin E, vitamin C, or multivitamins was not associated with a significant decrease in total CVD or CHD mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12090883", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1712, "text": "The American Heart Association has recommended consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but has made no recommendations regarding vitamin E supplementation for the general population. Although vitamin E supplementation seems to be safe for most people, recommendations from health care professionals should reflect the uncertainty of established benefit as demonstrated in clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11702901", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 961, "text": "Recent studies show that supplementation with antioxidant vitamins E and C have benefits in CHD prevention; however, supplementation with beta-carotene may have deleterious effects and is not recommended. Current evidence suggests that patients with CHD would probably benefit from taking vitamin E in a dosage of 400 IU per day and vitamin C in a dosage of 500 to 1,000 mg per day. Clinicians may also want to consider vitamin supplementation for CHD prevention in high-risk patients. Folate lowers elevated homocysteine levels, but evidence for routine supplemental use does not yet exist. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10498115", "endSection": "abstract" }, { "offsetInBeginSection": 1931, "offsetInEndSection": 2082, "text": "In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10639540", "endSection": "abstract" } ] }, { "body": "Which are the main functions of the human HuR (ELAVL1) protein in fibroblasts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12242302", "http://www.ncbi.nlm.nih.gov/pubmed/21816340", "http://www.ncbi.nlm.nih.gov/pubmed/20007147", "http://www.ncbi.nlm.nih.gov/pubmed/23837869", "http://www.ncbi.nlm.nih.gov/pubmed/11486028", "http://www.ncbi.nlm.nih.gov/pubmed/19252527", "http://www.ncbi.nlm.nih.gov/pubmed/10673359", "http://www.ncbi.nlm.nih.gov/pubmed/23155001", "http://www.ncbi.nlm.nih.gov/pubmed/24152440", "http://www.ncbi.nlm.nih.gov/pubmed/19345675", "http://www.ncbi.nlm.nih.gov/pubmed/9155038", "http://www.ncbi.nlm.nih.gov/pubmed/19884656", "http://www.ncbi.nlm.nih.gov/pubmed/17317627", "http://www.ncbi.nlm.nih.gov/pubmed/14530362", "http://www.ncbi.nlm.nih.gov/pubmed/23223443", "http://www.ncbi.nlm.nih.gov/pubmed/15036402", "http://www.ncbi.nlm.nih.gov/pubmed/12605686", "http://www.ncbi.nlm.nih.gov/pubmed/21164076", "http://www.ncbi.nlm.nih.gov/pubmed/9860962", "http://www.ncbi.nlm.nih.gov/pubmed/15863502", "http://www.ncbi.nlm.nih.gov/pubmed/12730239", "http://www.ncbi.nlm.nih.gov/pubmed/23401122", "http://www.ncbi.nlm.nih.gov/pubmed/10075998", "http://www.ncbi.nlm.nih.gov/pubmed/22446588", "http://www.ncbi.nlm.nih.gov/pubmed/15861128", "http://www.ncbi.nlm.nih.gov/pubmed/17288991", "http://www.ncbi.nlm.nih.gov/pubmed/9628881", "http://www.ncbi.nlm.nih.gov/pubmed/22310293", "http://www.ncbi.nlm.nih.gov/pubmed/21515253", "http://www.ncbi.nlm.nih.gov/pubmed/9763509", "http://www.ncbi.nlm.nih.gov/pubmed/22201738", "http://www.ncbi.nlm.nih.gov/pubmed/16639702", "http://www.ncbi.nlm.nih.gov/pubmed/15543229", "http://www.ncbi.nlm.nih.gov/pubmed/15824116", "http://www.ncbi.nlm.nih.gov/pubmed/19289500", "http://www.ncbi.nlm.nih.gov/pubmed/21745814", "http://www.ncbi.nlm.nih.gov/pubmed/17392515", "http://www.ncbi.nlm.nih.gov/pubmed/23508105" ], "ideal_answer": [ "HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich elements in their 3' untranslated regions and has been shown to shuttle between the nucleus and cytoplasm. HuR function was previously shown to be implicated in the maintenance of a \"young cell\" phenotype in models of replicative cellular senescence. Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence. Importantly, overexpression of HuR in senescent cells restored a \"younger\" phenotype, while a reduction in HuR expression accentuated the senescent phenotype. HuR associated with the 3' untranslated region of the mRNA encoding the longevity and stress-response protein SIRT1, stabilized the SIRT1 mRNA, and increased SIRT1 expression levels. In mesenchymal cells HuR plays a dominant role in lung development and as a key post-transcriptional regulator of networks guiding tissue remodeling during branching morphogenesis. In fibroblasts knockdown of HuR decreased the endogenous expression of TGF\u03b21 under exogenous TGF\u03b21 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression. HuR (human antigen R), represses ARF mRNA translation, thereby maintaining the replicative life span of mouse embryonic fibroblasts (MEFs). HuR is considered a global regulator of cell-cycle progression and tumorigenesis. Through its post-transcriptional influence on specific target mRNAs, HuR can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli." ], "concepts": [ "http://www.uniprot.org/uniprot/ELV1A_XENLA", "http://www.uniprot.org/uniprot/ELAV1_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005347", "http://www.uniprot.org/uniprot/ELV1B_XENLA", "http://www.uniprot.org/uniprot/ELAV1_XENTR", "http://www.uniprot.org/uniprot/ELAV1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051959" ], "type": "summary", "id": "533c394ec45e13371400000c", "snippets": [ { "offsetInBeginSection": 906, "offsetInEndSection": 1166, "text": "The H(2)O(2)-dependent sGC\u03b21 upregulation was attributable to sGC\u03b21 mRNA stabilization, conditioned by the translocation of the mRNA-binding protein HuR from the nucleus to the cytosol, and the increased mRNA binding of HuR to the sGC\u03b21 3' untranslated region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21164076", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1249, "text": "HuR silencing reversed the effects of H(2)O(2) on sGC\u03b21 levels and cGMP synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21164076", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1426, "text": "Our results identify H(2)O(2) as an endogenous mediator contributing to the regulation of vascular tone and point to a key role of HuR in sGC\u03b21 mRNA stabilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21164076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Cytoplasmic export of the RNA-binding protein HuR, a process that critically regulates its function, was recently shown to be inhibited by the AMP-activated protein kinase (AMPK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12730239", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 736, "text": "HuR function was previously shown to be implicated in the maintenance of a \"young cell\" phenotype in models of replicative cellular senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12730239", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1057, "text": "The in vitro binding selectivity of HuR is indicative of an ARE sequence's ability to destabilize a mRNA in vivo, suggesting a critical role for HuR in the regulation of mRNA degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9155038", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 869, "text": "urification and subsequent analyses demonstrate that this 32 kDa protein is identical to a recently identified member of the Elav-like gene family (ELG) called HuR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9155038", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1219, "text": "We also show that HuR can be induced to redistribute from the nucleus to the cytoplasm and that this redistribution is associated with an altered function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9628881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9628881", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is upregulated during serum stimulation and T cell activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9763509", "endSection": "title" }, { "offsetInBeginSection": 611, "offsetInEndSection": 808, "text": " HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich elements in their 3' untranslated regions and has been shown to shuttle between the nucleus and cytoplasm (18, 19).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9860962", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1142, "text": "We propose that HuR first may bind AU-rich element-containing mRNAs in the nucleus and then escort them through the nuclear pore, providing protection during and after export to the cytoplasmic compartment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9860962", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1355, "text": "Taken together, these data show that a correlation exists between the binding of HuR to the AU-rich motif in vitro and the destabilizing properties conferred by this sequence in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10075998", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 870, "text": "HuR interacts with AU-rich elements in the 3'UTR of many protooncogenes, cytokines, and transcription factors, thereby regulating the expression of these mRNAs on the posttranscriptional level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10673359", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1055, "text": "Transfection assays with a CAT reporter construct revealed reduced expression of the reporter, suggesting that HuR may be involved in the fine-tuning of the expression of the NF1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10673359", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 584, "text": "Importantly, overexpression of HuR in senescent cells restored a \"younger\" phenotype, while a reduction in HuR expression accentuated the senescent phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11486028", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 676, "text": "Our studies highlight a critical role for HuR during the process of replicative senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11486028", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 271, "text": "Here, using two models of replicative senescence, we describe the influence of the RNA-binding protein HuR in regulating the expression of several genes whose expression decreases during senescence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11486028", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 425, "text": "We demonstrate that HuR levels, HuR binding to target mRNAs encoding proliferative genes, and the half-lives of such mRNAs are lower in senescent cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11486028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11486028", "endSection": "title" }, { "offsetInBeginSection": 252, "offsetInEndSection": 579, "text": "Although in vitro experiments showed indiscriminate binding of Hu proteins synthesized in bacterial systems to many different AU-rich elements (AREs), in vivo studies have pointed to a cytoplasmic role for HuR protein in antagonizing the rapid decay of some specific ARE-containing mRNAs, depending on physiological situations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12242302", "endSection": "abstract" }, { "offsetInBeginSection": 1682, "offsetInEndSection": 1871, "text": "Our data suggest that the ARE-binding specificity of HuR in vivo is modulated to interact only with and thus regulate specific AREs in a cell type- and physiological state-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12242302", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1417, "text": "Overexpression of HuD and HuR in murine fibroblasts caused a striking stabilization of the endogenous MARCKS mRNA even under conditions when the MARCKS mRNA is normally actively degraded, i.e. after treating cells with phorbol ester. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12605686", "endSection": "abstract" }, { "offsetInBeginSection": 1675, "offsetInEndSection": 1824, "text": "Our findings implicate mRNA stabilization in the cytokine-mediated increase in eotaxin expression and strongly suggest a role for HuR in this effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14530362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Proteasome inhibition increases HuR level, restores heat-inducible HSP72 expression and thermotolerance in WI-38 senescent human fibroblasts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15036402", "endSection": "title" }, { "offsetInBeginSection": 648, "offsetInEndSection": 782, "text": "This result is consistent with the proposed role of HuR in assisting mRNA export to the cytoplasm and in antagonizing its degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15036402", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1147, "text": "HuR immunoprecipitations were positive for RhoB mRNA indicating an in vivo association, and Western blot analysis and immunofluorescence demonstrated that HuR rapidly partitions from the nucleus to the cytoplasm after UVL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15543229", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 327, "text": "In the cytosol, HuR is thought to function to control stability and translation of its ligand message. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15863502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "HuR is a ligand for nuclear mRNAs containing adenylate-uridylate-rich (ARE) elements in the 3'-untranslated region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16639702", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 229, "text": "Once bound to the mRNA, HuR is recognized by adapter proteins that then facilitate nuclear export of the complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16639702", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 332, "text": "In the cytosol, HuR is thought to function to control stability and translation of its ligand message.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16639702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "HuR is a ligand for nuclear mRNAs containing adenylate-uridylate rich elements in the 3'-untranslated region. Once bound to the mRNA, HuR is recognized by adapter proteins which then facilitate nuclear export of the complex. In the cytosol HuR is thought to function to control stability and translation of its ligand message.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17288991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "The RNA binding protein HuR regulates the stability of many target mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17317627", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 277, "text": "Here, we report that HuR associated with the 3' untranslated region of the mRNA encoding the longevity and stress-response protein SIRT1, stabilized the SIRT1 mRNA, and increased SIRT1 expression levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17317627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "In this study, we investigated the molecular mechanisms underlying the ATP analogue adenosine-5'-O-(3-thio)triphosphate-induced nucleocytoplasmic shuttling of the mRNA stabilizing factor HuR in human (h) mesangial cells (MC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17392515", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 402, "text": "HuR is an essential regulator of mesenchymal responses during lung branching.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21515253", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1382, "text": "Our data reveals HuR as the first RBP identified to play a dominant role in lung development and as a key post-transcriptional regulator of networks guiding tissue remodeling during branching morphogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21515253", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 338, "text": "Here we demonstrated a relevance for miR-9 in HL pathogenesis and identified two new targets Dicer1 and HuR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310293", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 882, "text": "We show that inhibition of miR-9 leads to derepression of DICER and HuR, which in turn results in a decrease in cytokine production by HL cells followed by an impaired ability to attract normal inflammatory cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "A conserved TGF\u03b21/HuR feedback circuit regulates the fibrogenic response in fibroblasts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446588", "endSection": "title" }, { "offsetInBeginSection": 623, "offsetInEndSection": 794, "text": "Knockdown of HuR decreased the endogenous expression of TGF\u03b21 under exogenous TGF\u03b21 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446588", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 977, "text": "Our study here established a TGF\u03b21/HuR feedback circuit regulating the fibrogenic response in fibroblasts, and targeting this feedback loop is of great potential to control fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446588", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 545, "text": "Here, we demonstrated that increased stabilization and subsequent over-expression of HuR mRNA were coupled to TTP deficiency. These findings were observed in breast cancer cell lines with an invasive phenotype and were further confirmed in ZFP36-knockout mouse fibroblasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401122", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 681, "text": "We show that TTP-HuR imbalance correlated with increased expression of AU-rich element (ARE) mRNAs that code for cancer invasion genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401122", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 472, "text": "Here, we show that an RNA-binding protein, HuR (human antigen R), represses ARF mRNA translation, thereby maintaining the replicative life span of mouse embryonic fibroblasts (MEFs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508105", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 813, "text": "The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced) with the nuclear hnRNP A1-RNP complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152440", "endSection": "abstract" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1312, "text": "The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle) indicating their concerted function in mRNA metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152440", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 303, "text": "Here, we show that overexpression of RNase L decreases cellular growth and downmodulates the RNA-binding protein, HuR, a regulator of cell-cycle progression and tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19252527", "endSection": "abstract" }, { "offsetInBeginSection": 1346, "offsetInEndSection": 1607, "text": "In sum, our results indicate that NO stabilizes mRNA subsets in fibroblasts, identify HuR as an RBP implicated in the NO response, reveal that HuR alone is insufficient for stabilizing several mRNAs by NO, and show that HO-1 induction by NO is regulated by HuR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289500", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 515, "text": "Suppression of HuR using siRNA resulted in an attenuation of the 3T3-L1 differentiation program, consistent with HuR control of the expression of mRNA ligand(s) critical to the differentiation process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19345675", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1024, "text": "In mouse embryonic fibroblasts, HuR bound to and stabilized the mRNA for Mdm2, a critical negative regulator of p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19884656", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1284, "text": "Our results reveal a positive feedback mechanism for the regulation of HuR, which may play an important role in the regulation of HuR during replicative senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20007147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "In dividing cells, the RNA-binding protein HuR associates with and stabilizes labile mRNAs encoding proliferative proteins, events that are linked to the increased cytoplasmic presence of HuR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824116", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 644, "text": "On the basis of these observations, we postulated a role for HuR in promoting the proliferation of vascular smooth muscle cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824116", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1323, "text": "We propose that HuR contributes to regulating hVSMC growth and homeostasis in pathologies associated with vascular smooth muscle proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Antiapoptotic function of RNA-binding protein HuR effected through prothymosin alpha.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15861128", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "We report the antiapoptotic effect of RNA-binding protein HuR, a critical regulator of the post-transcriptional fate of target transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15861128", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1143, "text": "Together, our data support a regulatory scheme whereby HuR binds the ProTalpha mRNA, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15861128", "endSection": "abstract" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1464, "text": "CARM1 represses replicative senescence by methylating HuR and thereby enhancing HuR's ability to regulate the turnover of cyclin A, cyclin B1, c-fos, SIRT1, and p16 mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23837869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "HuR, also known as Elavl1, is an RNA-binding protein that regulates embryonic development, progenitor cell survival, and cell stress responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23223443", "endSection": "abstract" }, { "offsetInBeginSection": 1735, "offsetInEndSection": 1912, "text": "Together, these studies reveal an evolutionarily conserved post-transcriptional mechanism involving competitive interactions between HuR and miR-200b that controls angiogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23223443", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1075, "text": "Immunoprecipitation of RNA-protein complexes and luciferase reporter assays indicate that HuR antagonizes the suppressive activity of miR-200b, down-regulates miR-200b expression, and promotes VEGF-A expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23223443", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 373, "text": "Here we present evidence that CUGBP1 and HuR jointly regulate the translation of occludin and play a crucial role in the maintenance of tight junction (TJ) integrity in the intestinal epithelial cell monolayer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23155001", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1279, "text": "These findings indicate that CUGBP1 represses occludin translation by increasing occludin mRNA recruitment to P-bodies, whereas HuR promotes occludin translation by blocking occludin mRNA translocation to P-bodies via the displacement of CUGBP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23155001", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 492, "text": "Through its post-transcriptional influence on specific target mRNAs, HuR can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22201738", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1106, "text": "We focus on HuR's well-recognized implication in cancer and chronic inflammation, and discuss emerging studies linking HuR to cardiovascular, neurological, and muscular pathologies. We also discuss the progress, potential, and challenges of targeting HuR therapeutically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22201738", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1347, "text": "These results indicate that HuR regulates occludin mRNA translation through Chk2-dependent HuR phosphorylation and that this influence is crucial for maintenance of the epithelial barrier integrity in the intestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745814", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 319, "text": "The RNA-binding protein HuR modulates the stability and translation of many target mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745814", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 459, "text": "Here, we investigated the role of HuR in the regulation of occludin expression and therefore in the intestinal epithelial barrier function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745814", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 552, "text": "HuR bound the 3'-untranslated region of the occludin mRNA and enhanced occludin translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745814", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 640, "text": "HuR association with the occludin mRNA depended on Chk2-dependent HuR phosphorylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745814", "endSection": "abstract" } ] }, { "body": "Which kinases does baricitinib inhibit?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24965573", "http://www.ncbi.nlm.nih.gov/pubmed/25431052", "http://www.ncbi.nlm.nih.gov/pubmed/26137574", "http://www.ncbi.nlm.nih.gov/pubmed/24818516", "http://www.ncbi.nlm.nih.gov/pubmed/23492738" ], "ideal_answer": [ "Baricitinib is an inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for JAK1 and JAK2." ], "exact_answer": [ [ "JAK1" ], [ "JAK2" ] ], "concepts": [ "http://www.uniprot.org/uniprot/JAK2_PONAB", "http://www.uniprot.org/uniprot/JAK2_PIG", "http://www.uniprot.org/uniprot/JAK2_MOUSE", "http://www.uniprot.org/uniprot/JAK2_CHICK", "http://www.uniprot.org/uniprot/JAK2_RAT", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053613", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053612", "http://www.uniprot.org/uniprot/JAK2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053614" ], "type": "list", "id": "56c8605b5795f9a73e000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137574", "endSection": "title" }, { "offsetInBeginSection": 314, "offsetInEndSection": 462, "text": "A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Baricitinib (also known as LY3009104 or INCB028050), a novel and potent small molecule inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for JAK1 and JAK2, is currently in clinical development for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24965573", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 585, "text": "A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical studies were conducted using the C3H/HeJ AA mouse model to assess the mechanism of clinical improvement by baricitinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137574", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 580, "text": "Phase II data for four JAK inhibitors (baricitinib,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24818516", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1088, "text": "Positive clinical trial results have also been reported for several other JAK inhibitors including baricitinib. Several other JAK inhibitors and other small molecular entities are also being developed in studies ranging from preclinical models to large clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23492738", "endSection": "abstract" } ] }, { "body": "Is there evidence to suggest that triiodothyronine has neuroprotective properties in traumatic brain injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9681483", "http://www.ncbi.nlm.nih.gov/pubmed/11719005", "http://www.ncbi.nlm.nih.gov/pubmed/12445968", "http://www.ncbi.nlm.nih.gov/pubmed/6798220", "http://www.ncbi.nlm.nih.gov/pubmed/23313345", "http://www.ncbi.nlm.nih.gov/pubmed/23601250", "http://www.ncbi.nlm.nih.gov/pubmed/839237", "http://www.ncbi.nlm.nih.gov/pubmed/7804793" ], "ideal_answer": [ "Yes, it has been demonstrated that triiodothyronine exerts neuroprotective properties in traumatic brain injury setting." ], "exact_answer": "yes", "type": "yesno", "id": "552010076b348bb82c000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23313345", "endSection": "title" }, { "offsetInBeginSection": 604, "offsetInEndSection": 797, "text": "Treatment with T3 (1.2\u03bcg/100g body weight, i.p.) 1h after TBI resulted in a significant improvement in motor and cognitive recovery after CCI, as well as in marked reduction of lesion volumes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23313345", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1433, "text": "Western blot analysis revealed the ability of T3 to reduce brain trauma through modulation of cytoplasmic-nuclear shuttling of nuclear factor-\u03baB (NF-\u03baB). Twenty-four hours after brain trauma, T3-treated mice also showed significantly lower number of TUNEL(+) apoptotic neurons and curtailed induction of Bax, compared to vehicle control. In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23313345", "endSection": "abstract" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 1798, "text": "The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12445968", "endSection": "abstract" }, { "offsetInBeginSection": 1651, "offsetInEndSection": 1864, "text": "The present study provides evidence that the peripheral nervous system has its own system responsible for the local production of 3,5,3'-triiodothyronine, which may play a key role during the regeneration process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11719005", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 554, "text": "Although it has been hypothesized that T3 may facilitate neuronal regeneration after CNS injury, the 5'-D2 response to brain injury is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9681483", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1097, "text": "The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7804793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The thyroid hormones triiodothyronine (T3) and L-thyroxine appear to enhance regeneration in the peripheral and central nervous system (CNS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6798220", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 946, "text": "T3 treatment influenced the general levels of incorporation of all treated groups over all days postoperation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6798220", "endSection": "abstract" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1459, "text": "T3 effects appear to involve an increased sensitivity of the cells of the injured nervous system to the hormone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6798220", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 791, "text": "T3, when administered over an 8 week period, stimulated axonal regeneration in the dorsal cortex and corpus callosum and promoted healing of the wound in the corpus callosum. The results of this investigation suggest that the use of T3 in the clinical treatment of injury to the central nervous system may be of less value than the work of earlier authors had indicated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/839237", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1433, "text": "In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23313345", "endSection": "abstract" } ] }, { "body": "What is the role played by mTOR in hypertrophic response and heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20644257" ], "ideal_answer": [ "When subjected to pressure overload, mTOR-ablated mice demonstrated an impaired hypertrophic response and accelerated heart failure progression. Thus, mTOR complex 1 signaling plays an important role in myocardial response to stress, to regulate cardiomyocyte viability and heart failure." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11984", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058570", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054144", "http://www.disease-ontology.org/api/metadata/DOID:9775" ], "type": "summary", "id": "5319a80fb166e2b80600002b", "snippets": [ { "offsetInBeginSection": 212, "offsetInEndSection": 287, "text": "Myocardial MTOR activity changes during hypertrophy and heart failure (HF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644257", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 927, "text": "When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644257", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1486, "text": "Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644257", "endSection": "abstract" } ] }, { "body": "Is Lysine-specific demethylase 1 (LSD1) a critical regulator of hematopoiesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "http://www.ncbi.nlm.nih.gov/pubmed/19736520", "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "http://www.ncbi.nlm.nih.gov/pubmed/23795291", "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "http://www.ncbi.nlm.nih.gov/pubmed/23147254", "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "http://www.ncbi.nlm.nih.gov/pubmed/22399799" ], "ideal_answer": [ "Yes. Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation of erythroid, granulomonocytic and megakaryocytic progenitors." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035162", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030097", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033193" ], "type": "yesno", "id": "553c011af321868558000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "title" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1317, "text": "shRNA-mediated knockdown of LSD1 in hematopoietic precursor cells resulted in altered SALL4 downstream gene expression and increased cellular activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1560, "text": "our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "title" }, { "offsetInBeginSection": 326, "offsetInEndSection": 405, "text": " LSD1 represents a central regulator of hematopoietic stem and progenitor cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 602, "text": " LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1123, "text": "LSD1-kd was associated with the upregulation of key hematopoietic genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1422, "text": "our findings distinguish LSD1 as a critical regulator of hematopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "title" }, { "offsetInBeginSection": 341, "offsetInEndSection": 778, "text": "Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 525, "text": "we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 871, "text": "we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1090, "text": "TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1507, "text": "the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "endSection": "title" }, { "offsetInBeginSection": 592, "offsetInEndSection": 740, "text": "Inhibition of CoREST and LSD1 perturbs differentiation of erythroid, megakaryocytic, and granulocytic cells as well as primary erythroid progenitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1140, "text": "we show that chromatin regulatory proteins CoREST and LSD1 mediate transcriptional repression by Gfi proteins. Lineage-restricted deployment of these cofactors through interaction with Gfi proteins controls hematopoietic differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1489, "text": "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "title" }, { "offsetInBeginSection": 547, "offsetInEndSection": 775, "text": "Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "endSection": "title" }, { "offsetInBeginSection": 1336, "offsetInEndSection": 1500, "text": "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" } ] }, { "body": "Is K-63 linked protein ubiquitination related to proteasomal degradation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18042044", "http://www.ncbi.nlm.nih.gov/pubmed/21737094", "http://www.ncbi.nlm.nih.gov/pubmed/19091944", "http://www.ncbi.nlm.nih.gov/pubmed/21071436", "http://www.ncbi.nlm.nih.gov/pubmed/15728425", "http://www.ncbi.nlm.nih.gov/pubmed/20663875" ], "ideal_answer": [ "Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism. Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a positive role in the canonical pathway that activates nuclear factor kappaB (NF-kappaB) through IkappaB kinase beta (IKKbeta), but a negative role in the noncanonical pathway that activates NF-kappaB through IKKalpha. These opposing roles of TRAF proteins may be linked to their ability to synthesize distinct forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20. Thus, ubiquitin chains are dynamic switches that can influence signaling outputs in dramatically different ways.In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes.", "In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes. Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism.", "One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism", "Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0061136", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016567", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010498" ], "type": "yesno", "id": "550899c92e93f0133a000003", "snippets": [ { "offsetInBeginSection": 236, "offsetInEndSection": 364, "text": "In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20663875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19091944", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1310, "text": "Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism. Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a positive role in the canonical pathway that activates nuclear factor kappaB (NF-kappaB) through IkappaB kinase beta (IKKbeta), but a negative role in the noncanonical pathway that activates NF-kappaB through IKKalpha. These opposing roles of TRAF proteins may be linked to their ability to synthesize distinct forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20. Thus, ubiquitin chains are dynamic switches that can influence signaling outputs in dramatically different ways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15728425", "endSection": "abstract" }, { "offsetInBeginSection": 1709, "offsetInEndSection": 1961, "text": "Importantly, although Lys-48-linked ubiquitin chains appear to trigger proteasomal degradation, the presence of Lys-63-linked ubiquitin chains suggests that ubiquitination of IP(3)Rs may have physiological consequences beyond signaling for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21071436", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 263, "text": "Chains of ubiquitin linked via lysine 48 (K48) are associated with protein degradation while chains linked via lysine 63 (K63) are associated with intracellular signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737094", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 481, "text": "Lys(48)-linked chains target proteins for proteasomal degradation, and Lys(63)-linked chains function in signal transduction, endocytosis and DNA repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18042044", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1535, "text": "Remarkably, the attached Lys-48- and Lys-63-linked ubiquitin chains are homogeneous and are segregated to separate IP(3)R subunits, and Lys-48-linked ubiquitin chains, but not Lys-63-linked chains, are required for IP(3)R degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21071436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Activated inositol 1,4,5-trisphosphate receptors are modified by homogeneous Lys-48- and Lys-63-linked ubiquitin chains, but only Lys-48-linked chains are required for degradation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21071436", "endSection": "title" } ] }, { "body": "Could transcription factors act as cell-cell signalling molecules?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14570063", "http://www.ncbi.nlm.nih.gov/pubmed/12386935" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0057877", "o": "D014157" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0127525", "o": "D014157" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0057942", "o": "D014157" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0127530", "o": "D014157" } ], "ideal_answer": [ "Yes. Recent data support the view that transcription factors - in particular, homeoproteins - can be transferred from cell to cell and have direct non-cell-autonomous (and therefore paracrine) activities.", "Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short-range cell-cell signalling molecules, hormones and structural proteins" ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0007267", "http://amigo.geneontology.org/amigo/term/GO:0006351", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157" ], "type": "yesno", "id": "56a7d32fa17756b72f000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short-range cell-cell signalling molecules, hormones and structural proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12386935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Recent data support the view that transcription factors - in particular, homeoproteins - can be transferred from cell to cell and have direct non-cell-autonomous (and therefore paracrine) activities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570063", "endSection": "abstract" } ] }, { "body": "Magnetic beads has been used in numerous applications. List some coatings used.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23326761", "http://www.ncbi.nlm.nih.gov/pubmed/22903707", "http://www.ncbi.nlm.nih.gov/pubmed/23176741", "http://www.ncbi.nlm.nih.gov/pubmed/22796092", "http://www.ncbi.nlm.nih.gov/pubmed/23021809", "http://www.ncbi.nlm.nih.gov/pubmed/23746403", "http://www.ncbi.nlm.nih.gov/pubmed/23149231", "http://www.ncbi.nlm.nih.gov/pubmed/23143268", "http://www.ncbi.nlm.nih.gov/pubmed/23401153", "http://www.ncbi.nlm.nih.gov/pubmed/23928048", "http://www.ncbi.nlm.nih.gov/pubmed/23877419", "http://www.ncbi.nlm.nih.gov/pubmed/23971905", "http://www.ncbi.nlm.nih.gov/pubmed/24291643", "http://www.ncbi.nlm.nih.gov/pubmed/23501439", "http://www.ncbi.nlm.nih.gov/pubmed/24224000", "http://www.ncbi.nlm.nih.gov/pubmed/23411631", "http://www.ncbi.nlm.nih.gov/pubmed/22841112", "http://www.ncbi.nlm.nih.gov/pubmed/23850993", "http://www.ncbi.nlm.nih.gov/pubmed/23845492", "http://www.ncbi.nlm.nih.gov/pubmed/23174509", "http://www.ncbi.nlm.nih.gov/pubmed/23934803", "http://www.ncbi.nlm.nih.gov/pubmed/24148457", "http://www.ncbi.nlm.nih.gov/pubmed/23378340", "http://www.ncbi.nlm.nih.gov/pubmed/23540244", "http://www.ncbi.nlm.nih.gov/pubmed/23598134", "http://www.ncbi.nlm.nih.gov/pubmed/23257838" ], "ideal_answer": [ "aptamers\nenzymes\nstreptavidin\nconcanavalin A\ncarboxylic-modified \nTiO2\nantibodies\nSELEX library\nsynthesized DNA\nC18\nC8\noligo(dT)" ], "exact_answer": [ [ "aptamers" ], [ "enzymes" ], [ "streptavidin" ], [ "concanavalin A" ], [ "carboxylic-modified" ], [ "TiO2" ], [ "antibodies" ], [ "SELEX library" ], [ "synthesized DNA" ], [ "C18" ], [ "C8" ], [ "oligo(dT)" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059346", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008280" ], "type": "list", "id": "550b0408c2af5d5b7000000c", "snippets": [ { "offsetInBeginSection": 539, "offsetInEndSection": 580, "text": "aptamer-based magnetic separation system ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291643", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 93, "text": "enzymes coated to magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148457", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 430, "text": " Aptamers are short, single-stranded (ss) oligonucleotidesable to recognize target molecules with high affinity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23971905", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 669, "text": " Recent developments involve immobilization of tagged enzymes onto magnetic nanoparticles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23934803", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 329, "text": "Using magnetic beads to immobilize DNAs containing various types of structures, we evaluated the in vitro binding activities of two well-characterized DNA repair proteins, Escherichia coli MutS and human p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "An affinity capture involved enzymatic assay for thrombin by using peptide aptamers as affinity ligands on magnetic beads", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877419", "endSection": "title" }, { "offsetInBeginSection": 166, "offsetInEndSection": 265, "text": "During phage selection the biotinylated antigens are bound to streptavidin coupled magnetic beads, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23850993", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 108, "text": " aptamer-functionalized magnetic beads ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845492", "endSection": "title" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1030, "text": "native antibody immobilized to magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22796092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Plasma membrane isolation using immobilized concanavalin A magnetic beads.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903707", "endSection": "title" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1018, "text": "streptavidin magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903707", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 420, "text": " Digoxin was coated onto the surface of streptavidin magnetic beads. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23021809", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 582, "text": "covalent immobilization of the antigen onto carboxylic-modified magnetic beads (HOOC-MBs) activated with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS), and further incubation in a mixture solution containing variable concentrations of the antigen and a fixed concentration of an HRP-labeled detection antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746403", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 441, "text": "Aptamers against HNE were immobilized on magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23598134", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 269, "text": "The high specificity was obtained by using the magnetic beads and aptamers,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23540244", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 620, "text": "Multiple targets (maltase, invertase, lipase) were immobilized on the magnetic beads by covalent linkage using 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as reaction reagents, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23501439", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 629, "text": "TiO2 -coated magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401153", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 51, "text": "antibody-targeted magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378340", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 478, "text": "A special SELEX library was constructed with the aim to immobilize this library on magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326761", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 443, "text": "streptavidin-coupled magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257838", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 488, "text": "aptamers loaded on the magnetic beads ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176741", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 418, "text": "His-affinity magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23174509", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 415, "text": "treptavidin-coated magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23149231", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 549, "text": ", synthesized DNA is bound to magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23143268", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 185, "text": "streptavidin-modified magnetic microbeads ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841112", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 448, "text": "oligo(dT) magnetic beads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411631", "endSection": "abstract" } ] }, { "body": "is pharmacological treatment of subclinical hypothyroidism effective in reducing cardiovascular events?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20807695", "http://www.ncbi.nlm.nih.gov/pubmed/16259335", "http://www.ncbi.nlm.nih.gov/pubmed/23559085", "http://www.ncbi.nlm.nih.gov/pubmed/16542047", "http://www.ncbi.nlm.nih.gov/pubmed/22529180", "http://www.ncbi.nlm.nih.gov/pubmed/16026106", "http://www.ncbi.nlm.nih.gov/pubmed/23369134", "http://www.ncbi.nlm.nih.gov/pubmed/17636722", "http://www.ncbi.nlm.nih.gov/pubmed/21823062", "http://www.ncbi.nlm.nih.gov/pubmed/19463607", "http://www.ncbi.nlm.nih.gov/pubmed/23252247", 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unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559085", "endSection": "abstract" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1891, "text": "The lack of specific randomized trials enrolling either old or very old subjects, aimed at evaluate the efficacy of hormonal replacement on overall survival and cardiovascular risk reduction along with the negative effects of possible over-treatment, makes the decision to treat older people a still unresolved clinical challenge", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23369134", "endSection": "abstract" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1035, "text": "In patients with type 2 DM, the presence of SH serves as an additional risk factor for endothelial dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23252247", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1673, "text": "Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22529180", "endSection": "abstract" }, { "offsetInBeginSection": 1498, "offsetInEndSection": 1695, "text": "Subclinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events, especially stroke in older adults from the general population with normal left ventricular function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21823062", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1709, "text": "SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463607", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1341, "text": "In CHF patients TSH levels even slightly above normal range are independently associated with a greater likelihood of heart failure progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19006851", "endSection": "abstract" }, { "offsetInBeginSection": 2028, "offsetInEndSection": 2309, "text": "In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17636722", "endSection": "abstract" }, { "offsetInBeginSection": 2028, "offsetInEndSection": 2423, "text": "However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16542047", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1633, "text": "However, whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16026106", "endSection": "abstract" } ] }, { "body": "Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)\ncause sudden cardiac death?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24076290", "http://www.ncbi.nlm.nih.gov/pubmed/22050625", "http://www.ncbi.nlm.nih.gov/pubmed/18684293", "http://www.ncbi.nlm.nih.gov/pubmed/19601860", "http://www.ncbi.nlm.nih.gov/pubmed/19564966", "http://www.ncbi.nlm.nih.gov/pubmed/15890976", "http://www.ncbi.nlm.nih.gov/pubmed/18483626", "http://www.ncbi.nlm.nih.gov/pubmed/19575158", "http://www.ncbi.nlm.nih.gov/pubmed/19568611", "http://www.ncbi.nlm.nih.gov/pubmed/19631908", "http://www.ncbi.nlm.nih.gov/pubmed/20513597", "http://www.ncbi.nlm.nih.gov/pubmed/17959506", "http://www.ncbi.nlm.nih.gov/pubmed/24011300", "http://www.ncbi.nlm.nih.gov/pubmed/20361477", "http://www.ncbi.nlm.nih.gov/pubmed/22995932", "http://www.ncbi.nlm.nih.gov/pubmed/20143088", "http://www.ncbi.nlm.nih.gov/pubmed/19781797", "http://www.ncbi.nlm.nih.gov/pubmed/21616285", "http://www.ncbi.nlm.nih.gov/pubmed/22524859", "http://www.ncbi.nlm.nih.gov/pubmed/20091251", "http://www.ncbi.nlm.nih.gov/pubmed/22119737", "http://www.ncbi.nlm.nih.gov/pubmed/21893508", "http://www.ncbi.nlm.nih.gov/pubmed/22307399", "http://www.ncbi.nlm.nih.gov/pubmed/21872879", "http://www.ncbi.nlm.nih.gov/pubmed/19345240", "http://www.ncbi.nlm.nih.gov/pubmed/22749309", "http://www.ncbi.nlm.nih.gov/pubmed/23286974", "http://www.ncbi.nlm.nih.gov/pubmed/12837242", "http://www.ncbi.nlm.nih.gov/pubmed/23040497", "http://www.ncbi.nlm.nih.gov/pubmed/12574890", "http://www.ncbi.nlm.nih.gov/pubmed/22993115", "http://www.ncbi.nlm.nih.gov/pubmed/15749201", "http://www.ncbi.nlm.nih.gov/pubmed/17052226", "http://www.ncbi.nlm.nih.gov/pubmed/21135804", "http://www.ncbi.nlm.nih.gov/pubmed/21292648", "http://www.ncbi.nlm.nih.gov/pubmed/11807805", "http://www.ncbi.nlm.nih.gov/pubmed/23094885", "http://www.ncbi.nlm.nih.gov/pubmed/12386154" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11993336", "o": "114251.0001" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1861943", "o": "http://linkedlifedata.com/resource/umls/label/A11993336" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1861943", "o": "http://linkedlifedata.com/resource/umls/label/A16614236" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1861943", "o": "http://linkedlifedata.com/resource/umls/label/A16614236" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11993336", "o": "CASQ2, ASP307HIS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16614236", "o": "VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 2; 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Stress or anxiety-induced release of endogenous catecholamines causes a dysfunction in the myocytic calcium-ion channel, leading to ventricular arrhythmias that can cause dizziness, syncope, or sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24011300", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1607, "text": "During a follow-up of 48\u00b194 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286974", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 500, "text": "We report a family with repeat events of sudden cardiac death and recurrent ventricular fibrillation in a teenage girl, where autopsy data and clinical investigations were inconclusive. The diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was established only following finding a gene mutation in the cardiac ryanodine receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23094885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040497", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 593, "text": "catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS), leave no evidence to be found at autopsy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22993115", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 511, "text": "a spectrum of sudden cardiac death (SCD)-predisposing heritable cardiac arrhythmia syndromes, including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995932", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 344, "text": "CPVT is a familial arrhythmogenic syndrome characterized by abnormal calcium (Ca(2+)) handling, ventricular arrhythmias, and sudden cardiac death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749309", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 832, "text": "Mutations in RyR2 are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT) and sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22524859", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 537, "text": "Patients with CPVT often present with exercise- or emotion induced syncope, the first presentation can also be sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22119737", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 348, "text": "Among the five major arrhythmogenic disorders occurring in the absence of a structural heart disease is catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a highly lethal form of inherited arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22050625", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 376, "text": "Patients with CPVT are at high risk of developing life-threatening ventricular arrhythmias when untreated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by VT induced by adrenergic stress in the absence of structural heart disease and high incidence of sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21872879", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 470, "text": "CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca(2+) release channels. Sudden cardiac death is incompletely prevented by conventional drug therapy with \u03b2-blockers with or without Ca(2+) channel blockers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21616285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21292648", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 349, "text": "Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome and catecholaminergic polymorphic ventricular tachyarrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21135804", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 425, "text": "catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) are primary inherited arrhythmia syndromes that may cause syncope and sudden cardiac death in young individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20513597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20361477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder that causes syncopal episodes related with stress or emotion and even sudden cardiac deaths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20143088", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 190, "text": "Catecholaminergic polymorphic ventricular tachycardia caused by mutations in the RyR2 gene manifests as severe arrhythmias, and may provide a candidate for sudden cardiac deaths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19781797", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 306, "text": "Patients diagnosed with an electrical cardiomyopathy have an increased risk of syncope and sudden cardiac death (SCD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20091251", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1399, "text": "Patients with CPVT present with exercise-induced syncope and sudden cardiac death but normal resting electrocardiograms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19631908", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 820, "text": "Over 80% of SCD occurs in patients with organic heart disease. However, approximately 10-15% of SCD occurs in the presence of structurally normal heart and the majority of those patients are young. In this group of patients, changes in genes encoding cardiac ion channels produce modification of the function of the channel resulting in an electrophysiological substrate of VA and SCD. Collectively these disorders are referred to as Cardiac Ion Channelopathies. The 4 major syndromes in this group are: The Long QT Syndrome (LQTS), the Brugada Syndrome (BrS), the Short QT Syndrome (SQTS), and the Catecholaminergic Polymorphic VT (CPVT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19601860", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 365, "text": "Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome (SQTS), and catecholaminergic polymorphic ventricular tachyarrhythmias (CPVT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19575158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. It occurs in patients with structurally normal heart and causes exercise-emotion-triggered syncope and sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19568611", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 879, "text": "Potentially lethal ion channel disorders (channelopathies) such as the long QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19564966", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 513, "text": "Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 contributes to the formation of delayed after-depolarisations, which are thought to underlie the fatal arrhythmia that occurs in both heart failure (HF) and in catecholaminergic polymorphic ventricular tachycardia (CPVT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19345240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18684293", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 287, "text": "Mutations in RyR2 have been linked to exercise-induced sudden cardiac death (catecholaminergic polymorphic ventricular tachycardia [CPVT]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a heritable arrhythmia unmasked by exertion or stress, characterized by triggered activity and sudden cardiac death in affected patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17959506", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 692, "text": "families that exhibit CPVT (catecholaminergic polymorphic ventricular tachycardia), a condition in which physical or emotional stress can trigger severe tachyarrhythmias that can lead to sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17052226", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1432, "text": "that often leads to sudden death in HF and in CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17052226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15890976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15749201", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1128, "text": "These data suggest that \"leaky\" RyR2 channels can trigger fatal cardiac arrhythmias, providing a possible explanation for CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12837242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by syncopal events and sudden cardiac death at a young age during physical stress or emotion, in the absence of structural heart disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12386154", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 355, "text": " catecholaminergic polymorphic ventricular tachycardia (CPVT), idiopathic ventricular fibrillation (VF), and arrhythmogenic right ventricular cardiomyopathy (ARVC) account for a relevant proportion of sudden cardiac death cases in young patients cohorts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12574890", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 284, "text": "has recently been shown to be involved in at least two forms of sudden cardiac death (SCD): (1) Catecholaminergic polymorphic ventricular tachycardia (CPVT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11807805", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of DNA topoisomerase II inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8824770", "http://www.ncbi.nlm.nih.gov/pubmed/23715267" ], "ideal_answer": [ "DNA topoisomerase II inhibitors eliminate cancer cells by causing DNA double-strand breaks, finally leading to apoptotic cell death. Moreover, drug-induced histone eviction was also shown to be associated with attenuated DNA repair, epigenetic changes and transcpription deregulation." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008657", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059003", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003918", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059005", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003916", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008156", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000371", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004250", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026942" ], "type": "summary", "id": "5312f0f0e3eabad02100000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "DNA topoisomerase II inhibitors are a major class of cancer chemotherapeutics, which are thought to eliminate cancer cells by inducing DNA double-strand breaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23715267", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 597, "text": "We show that anthracyclines promote histone eviction irrespective of their ability to induce DNA double-strand breaks. The histone variant H2AX, which is a key component of the DNA damage response, is also evicted by anthracyclines, and H2AX eviction is associated with attenuated DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23715267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Induction of apoptotic cell death by DNA topoisomerase II inhibitors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8824770", "endSection": "title" }, { "offsetInBeginSection": 659, "offsetInEndSection": 766, "text": "The results we have obtained clearly indicate that topoisomerase II poisons induce cell death by apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8824770", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 660, "text": "Histone eviction deregulates the transcriptome in cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23715267", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 988, "text": "We define a novel mechanism of action of anthracycline anticancer drugs doxorubicin and daunorubicin on chromatin biology, with important consequences for DNA damage responses, epigenetics, transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23715267", "endSection": "abstract" } ] }, { "body": "Are histone deacetylase (HDAC) inhibitors good candidates to control metastasis of solid tumors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19417021", "http://www.ncbi.nlm.nih.gov/pubmed/20884621", "http://www.ncbi.nlm.nih.gov/pubmed/22279574", "http://www.ncbi.nlm.nih.gov/pubmed/21041383", "http://www.ncbi.nlm.nih.gov/pubmed/22038994", "http://www.ncbi.nlm.nih.gov/pubmed/22811583", "http://www.ncbi.nlm.nih.gov/pubmed/10893438", "http://www.ncbi.nlm.nih.gov/pubmed/15800932", "http://www.ncbi.nlm.nih.gov/pubmed/21452015", "http://www.ncbi.nlm.nih.gov/pubmed/22161747", "http://www.ncbi.nlm.nih.gov/pubmed/19789319", "http://www.ncbi.nlm.nih.gov/pubmed/19509253", "http://www.ncbi.nlm.nih.gov/pubmed/18981013", "http://www.ncbi.nlm.nih.gov/pubmed/19861438", "http://www.ncbi.nlm.nih.gov/pubmed/18506586", "http://www.ncbi.nlm.nih.gov/pubmed/15318170" ], "ideal_answer": [ "Yes, some HDAC inhibitors, such as Vorinostat, are on trial for human treatment after proving successful in animal models. Combination with other drugs is likely to be needed to control metastasis." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056572" ], "type": "yesno", "id": "517404878ed59a060a000023", "snippets": [ { "offsetInBeginSection": 1227, "offsetInEndSection": 1375, "text": "JNJ-26481585 also fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again 5-fluorouracil/Leucovorin showed modest activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19861438", "endSection": "sections.0" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1722, "text": "Although not meeting the RECIST response criteria for adequate single-agent activity, the observed tolerable toxicities and the potential for clinical benefit in terms of stable disease suggest that further assessment of vorinostat as a part of combination therapy with either chemotherapeutic or targeted agents in metastatic breast might be undertaken.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18981013", "endSection": "sections.0" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1832, "text": "Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22811583", "endSection": "sections.0" }, { "offsetInBeginSection": 1396, "offsetInEndSection": 1665, "text": "mRNA expression analysis of lung tumor bearing mice suggested that the enhanced chemopreventive activity of the combination is related to atorvastatin modulation of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating invasion and metastasis pathways.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22161747", "endSection": "sections.0" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1268, "text": "Histone deacetylase (HDAC) inhibitors induced morphologic differentiation, cell-cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. VPA inhibited the growth of UM tumors in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038994", "endSection": "sections.0" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1422, "text": "When both drugs were used in concert additive effects were observed on the migratory and invasive behavior but not on tumor-endothelium and tumor-matrix interaction. Separate mTOR or HDAC inhibition slows processes related to tumor metastasis. The RAD001-VPA combination showed advantage over VPA monotreatment with particular respect to migration and invasion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21452015", "endSection": "sections.0" }, { "offsetInBeginSection": 1555, "offsetInEndSection": 1793, "text": "In conclusion, sequential treatments of mice with MS-275 followed by TRAIL may target multiple pathways to reverse EMT and inhibit tumor progression, angiogenesis, and metastasis and represent a novel therapeutic approach to treat cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21041383", "endSection": "sections.0" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1425, "text": "In vivo, AA98 synergized with vorinostat to inhibit tumor growth and metastasis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20884621", "endSection": "sections.0" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1782, "text": "We report the first preclinical data for the prevention of brain metastasis of triple-negative breast cancer. Vorinostat is brain permeable and can prevent the formation of brain metastases by 62%. Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19789319", "endSection": "sections.0" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1616, "text": "Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509253", "endSection": "sections.0" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1748, "text": "Although single-agent PCI-24781 had modest effects on STS growth and metastasis, marked inhibition was observed when combined with chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417021", "endSection": "sections.0" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1367, "text": "In a 4T1 metastatic breast carcinoma model, AN-7 inhibited the formation of lung lesions by 76% and AN-9 by 47%, further demonstrating the greater efficacy of AN-7 compared to AN-9 (P<0.02). Both AN-7 and AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression and HIF-1alpha.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18506586", "endSection": "sections.0" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1507, "text": "Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg AN-7 did not cause adverse effects and the former exhibited significant anticancer activity, AN-7 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15800932", "endSection": "sections.0" }, { "offsetInBeginSection": 435, "offsetInEndSection": 801, "text": "We show that apicidin significantly inhibits H-ras-induced invasive phenotype of MCF10A human breast epithelial cells in parallel with a specific downregulation of matrix metalloproteinase (MMP)-2, but not MMP-9. We also show that apicidin induces a morphological reversal and growth inhibition of H-ras MCF10A cells similar to that induced by other HDAC inhibitors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10893438", "endSection": "sections.0" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1553, "text": "We also found that NaB induced three genes, which are known metastatic suppressors, and downregulated 11 genes, which have been shown to promote metastasis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15318170", "endSection": "sections.0" } ] }, { "body": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16228909", "http://www.ncbi.nlm.nih.gov/pubmed/22421737", "http://www.ncbi.nlm.nih.gov/pubmed/15978612", "http://www.ncbi.nlm.nih.gov/pubmed/15639480", "http://www.ncbi.nlm.nih.gov/pubmed/11788418", "http://www.ncbi.nlm.nih.gov/pubmed/21562304", "http://www.ncbi.nlm.nih.gov/pubmed/21484537", "http://www.ncbi.nlm.nih.gov/pubmed/15205937", "http://www.ncbi.nlm.nih.gov/pubmed/18083727", "http://www.ncbi.nlm.nih.gov/pubmed/22371524", "http://www.ncbi.nlm.nih.gov/pubmed/14567970", "http://www.ncbi.nlm.nih.gov/pubmed/16352453", "http://www.ncbi.nlm.nih.gov/pubmed/12642359", "http://www.ncbi.nlm.nih.gov/pubmed/18505755", "http://www.ncbi.nlm.nih.gov/pubmed/12397030", "http://www.ncbi.nlm.nih.gov/pubmed/17535853", "http://www.ncbi.nlm.nih.gov/pubmed/24860983" ], "ideal_answer": [ "The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function.", "Yes, Muscle LIM protein is involved in cardiomyopathies. In specific, the skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy. MLP became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.disease-ontology.org/api/metadata/DOID:0050700" ], "type": "yesno", "id": "54f704b630767eb92e000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421737", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 100, "text": "Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371524", "endSection": "abstract" }, { "offsetInBeginSection": 1710, "offsetInEndSection": 1858, "text": "A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371524", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 317, "text": "Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21562304", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1390, "text": "Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21562304", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 1110, "text": "Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674-2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78-85, 2006; Geier et al. Circulation 107:1390-1395, 2003; Hershberger et al. Clin Transl Sci 1:21-26, 2008; Kn\u00f6ll et al. Cell 111:943-955, 2002; Kn\u00f6ll et al. Circ Res 106:695-704, 2010; Mohapatra et al. Mol Genet Metab 80:207-215, 2003).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21484537", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 513, "text": "MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393-403, 1997). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21484537", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 459, "text": "Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505755", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 1124, "text": "We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505755", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18083727", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1156, "text": "Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18083727", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535853", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 370, "text": "TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathy-associated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16352453", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1883, "text": "Approximately 4.1% of unrelated patients had HCM-associated MLP or TCAP mutations. MLP/TCAP-HCM phenotypically mirrors myofilament-HCM and is more severe than the subset of patients who still remain without a disease-causing mutation. The precise role of W4R-MLP in the pathogenesis of either DCM or HCM warrants further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16352453", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1487, "text": "MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16228909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15978612", "endSection": "abstract" }, { "offsetInBeginSection": 1307, "offsetInEndSection": 1660, "text": "In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15978612", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 280, "text": "Mice lacking the muscle LIM protein (MLP) develop morphological and clinical signs resembling human dilated cardiomyopathy and heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15639480", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1772, "text": "Our results show that the absence of MLP causes a local loss of mitochondria. We hypothesize that this is caused by a disturbed interaction between cytoskeleton and mitochondria, which interferes with energy sensing and energy transfer. Recovery of energy depletion by stimulating mitochondrial biogenesis might be a useful therapeutic strategy for improving the energy imbalance in heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15639480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15205937", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1092, "text": "The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15205937", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 572, "text": "Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly. In the latter role, it binds zyxin and alpha-actinin, both of which are involved in actin organization. An MLP-deficient mouse has been described; these mice develop dilated cardiomyopathy and heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14567970", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 896, "text": "We identified a patient with DCM and EFE, having a mutation in MLP with the residue lysine 69 substituted by arginine (K69R). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14567970", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 402, "text": "MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12642359", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1365, "text": "Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12642359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12397030", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 412, "text": "Targeted disruption of muscle LIM protein (MLP) has previously been shown to result in dilated cardiomyopathy with many of the clinical signs of heart failure, although the effects of MLP disruption on passive ventricular mechanics and myocyte architecture are not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11788418", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1189, "text": "These results suggest that the disruption of the cytoskeletal protein MLP results in less compliant passive tissue and concomitant structural alterations in the three-dimensional myocyte architecture that may in part explain the ventricular dysfunction in the dilated heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11788418", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 347, "text": " Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24860983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15205937", "endSection": "abstract" } ] }, { "body": "Which gene harbors the mutation T790M?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25667490", "http://www.ncbi.nlm.nih.gov/pubmed/25384171", "http://www.ncbi.nlm.nih.gov/pubmed/26056478", "http://www.ncbi.nlm.nih.gov/pubmed/25682017", "http://www.ncbi.nlm.nih.gov/pubmed/25806347", "http://www.ncbi.nlm.nih.gov/pubmed/25483995", "http://www.ncbi.nlm.nih.gov/pubmed/25323938", "http://www.ncbi.nlm.nih.gov/pubmed/25939061", "http://www.ncbi.nlm.nih.gov/pubmed/26124670", "http://www.ncbi.nlm.nih.gov/pubmed/26058074", "http://www.ncbi.nlm.nih.gov/pubmed/26396685", "http://www.ncbi.nlm.nih.gov/pubmed/25382705" ], "ideal_answer": [ "The T790M mutation refers to the mutation in exon 20 of the EGFR gene" ], "exact_answer": [ "EGFR", "epidermal growth factor receptor" ], "type": "factoid", "id": "56d1f790f22319765a000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Nearly one half of all cases of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non-small-cell lung cancer (NSCLC) are due to the T790M mutation in EGFR exon 20. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25682017", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 306, "text": "Two types of epidermal growth factor receptor (EGFR) mutations in exon 19 and exon 21 (ex19del and L858R) are prevalent in lung cancer patients and sensitive to targeted EGFR inhibition. A resistance mutation in exon 20 (T790M) has been found to accompany drug treatment when patients relapse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26124670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25939061", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 298, "text": "However, resistance to the EGFR TKIs develops mostly secondary to T790M mutation in exon 20. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26056478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The T790M mutation in EGFR accounts for approximately half of all lung cancer cases with acquired resistance to the current clinical EGFR tyrosine kinase inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26058074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "In nonsmall cell lung cancer (NSCLC), the threonine(790)-methionine(790) (T790M) point mutation of EGFR kinase is one of the leading causes of acquired resistance to the first generation tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26396685", "endSection": "abstract" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1232, "text": "Both AKT and MEK inhibition contributed to cell death independent of erlotinib in the T790M-containing H1975 and the EGFR-WT cell lines tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25323938", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 388, "text": " The EGFR T790M mutation is generally considered to be the molecular genetic basis of acquired TKI resistance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25667490", "endSection": "title" }, { "offsetInBeginSection": 690, "offsetInEndSection": 816, "text": "In EGFR-mutated NSCLC cell lines with the acquired resistance threonine-to-methionine mutation in codon 790 (T790M) mutation, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25384171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "To overcome T790M-mediated acquired resistance of lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), second generation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25382705", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 679, "text": "Approximately 50% of cases of acquired resistance (AR) are due to a secondary T790M mutation in exon 20 of the EGFR gene;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25806347", "endSection": "abstract" } ] }, { "body": "what is the role of FGF-2 in cardiac regeneration after myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17693930", "http://www.ncbi.nlm.nih.gov/pubmed/22146760", "http://www.ncbi.nlm.nih.gov/pubmed/16581974", "http://www.ncbi.nlm.nih.gov/pubmed/21422919", "http://www.ncbi.nlm.nih.gov/pubmed/12580776", "http://www.ncbi.nlm.nih.gov/pubmed/12091808" ], "ideal_answer": [ "Exogenous FGF-2 was shown to increase angiogenesis and myocardial perfusion, promote myocardial regeneration by activating the SDF-1\u03b1/CXCR4 axis, and thereby improve the cardiac function after myocardial infarction. Furthermore, prevascularization with basic FGF-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. In another study, transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) was shown to promote Cardiac Progenitor Cells proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following myocardial infarction and improving cardiac function." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016222", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ], "type": "summary", "id": "52f3a9ef2059c6d71c000012", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 263, "text": "To investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22146760", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1505, "text": "The new method has shown to be capable of promoting CSCs proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and improving cardiac function. This may provide a new strategy for myocardial regeneration following AMI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22146760", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 156, "text": "To investigate the effects of exogenous basic fibroblast growth factor (bFGF) on myocardial regeneration after acute myocardial infarction (AMI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21422919", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1538, "text": "Exogenous bFGF was shown to have increased angiogenesis and myocardial perfusion, promoted myocardial regeneration by activating the SDF-1\u03b1/CXCR4 axis, and thereby improved the cardiac function, which may provide a new therapeutic strategy for AMI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21422919", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1429, "text": "Support to the paracrine hypothesis is provided by data showing that several genes, coding for factors (VEGF, FGF-2, HGF, IGF-I, and TB4) that are potential mediators of the effects exerted by the Akt-MSC conditioned medium, are significantly up-regulated in the Akt-MSCs, particularly in response to hypoxia. Taken together, our data support Akt-MSC-mediated paracrine mechanisms of myocardial protection and functional improvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16581974", "endSection": "abstract" }, { "offsetInBeginSection": 1632, "offsetInEndSection": 1895, "text": "Prevascularization with basic fibroblast growth factor-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. We expect that this system will contribute to regeneration medicine through its extensive application to other growth factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12091808", "endSection": "abstract" } ] }, { "body": "Have 5q35 microdeletions been implicated in Sotos syndrome development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25510705", "http://www.ncbi.nlm.nih.gov/pubmed/18505455", "http://www.ncbi.nlm.nih.gov/pubmed/12900893", "http://www.ncbi.nlm.nih.gov/pubmed/16140999", "http://www.ncbi.nlm.nih.gov/pubmed/23190751", "http://www.ncbi.nlm.nih.gov/pubmed/15805156", "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "http://www.ncbi.nlm.nih.gov/pubmed/24192683", "http://www.ncbi.nlm.nih.gov/pubmed/22012791", "http://www.ncbi.nlm.nih.gov/pubmed/23913520" ], "ideal_answer": [ "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID).", "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID)" ], "exact_answer": "yes", "type": "yesno", "id": "571f33f10fd6f91b68000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 684, "text": "We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with developmental delay, hypotonia and multiple minor anomalies. Comparison of her phenotype with the few published patients with terminal 5q35 deletions revealed several overlapping features, but also showed remarkable differences such as shortness of stature versus macrosomia. After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes. We demonstrated that the deletion in our patient is immediately adjacent to the reported Sotos syndrome deletion site", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12900893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805156", "endSection": "title" }, { "offsetInBeginSection": 564, "offsetInEndSection": 776, "text": "After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12900893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190751", "endSection": "title" }, { "offsetInBeginSection": 302, "offsetInEndSection": 479, "text": "Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 330, "text": "Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Alu-related 5q35 microdeletions in Sotos syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505455", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805156", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190751", "endSection": "title" }, { "offsetInBeginSection": 103, "offsetInEndSection": 216, "text": "Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24192683", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 313, "text": "Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 312, "text": "There are two types of mutations that cause NSD1 haploinsufficiency: mutations within the NSD1 gene (mutation type) and a 5q35 submicroscopic deletion encompassing the entire NSD1 gene (deletion type). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22012791", "endSection": "abstract" }, { "offsetInBeginSection": 1350, "offsetInEndSection": 1458, "text": "aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805156", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24192683", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140999", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1424, "text": "aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Alu-related 5q35 microdeletions in Sotos syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505455", "endSection": "title" } ] }, { "body": "Tumors of which three organs are classically associated with the multiple endocrine neoplasia type 1 syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23279763", "http://www.ncbi.nlm.nih.gov/pubmed/10664520", "http://www.ncbi.nlm.nih.gov/pubmed/9820618", "http://www.ncbi.nlm.nih.gov/pubmed/17455252", "http://www.ncbi.nlm.nih.gov/pubmed/23024266", "http://www.ncbi.nlm.nih.gov/pubmed/20175448", "http://www.ncbi.nlm.nih.gov/pubmed/11914929", "http://www.ncbi.nlm.nih.gov/pubmed/18172277", "http://www.ncbi.nlm.nih.gov/pubmed/9236523", "http://www.ncbi.nlm.nih.gov/pubmed/21302639", "http://www.ncbi.nlm.nih.gov/pubmed/23435440", "http://www.ncbi.nlm.nih.gov/pubmed/10614532", "http://www.ncbi.nlm.nih.gov/pubmed/7962349", "http://www.ncbi.nlm.nih.gov/pubmed/21613051", "http://www.ncbi.nlm.nih.gov/pubmed/9735087", "http://www.ncbi.nlm.nih.gov/pubmed/10496602", "http://www.ncbi.nlm.nih.gov/pubmed/10502325" ], "ideal_answer": [ "Multiple endocrine neoplasia type 1 syndrome is an inherited cancer syndrome defined by occurrence of multiple neuro-endocrine tumors and is classically associated with the combined occurrence of two or more tumors involving parathyroid gland, pancreas and pituitary gland. Other tumors, including but not limited to adrenal cortical tumor, carcinoid tumors lipoma, leiomyoma, duodenal gastrinoma, hepatic focal nodular hyperplasia, and renal angiomyolipoma, angiofibroma, colagenoma, thyroid tumor and meningioma, may also be present." ], "exact_answer": [ [ "parathyroid gland" ], [ "pancreas" ], [ "pituitary gland" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018761" ], "type": "list", "id": "51477de5d24251bc05000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Multiple endocrine neoplasia type 1 (MEN1; formerly known as Wermer syndrome) is a rare disorder characterized by the combined occurrence of two or more tumors involving parathyroid, pancreatic islets and anterior pituitary glands; some other tumors have also been described.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435440", "endSection": "sections.0" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1154, "text": " Hyperparathyroidism is the most common feature of MEN1 (95% of patients), pancreatic islet tumors or pancreatic NET (neuroendocrine tumor) occur in 40-70% and pituitary tumors in 30-40% of MEN 1 patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435440", "endSection": "sections.0" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1302, "text": " In addition, other tumors, such as adrenal cortical tumors, carcinoid tumors, lipomas, angiofibromas, colagenomas and meningiomas may be present. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435440", "endSection": "sections.0" }, { "offsetInBeginSection": 1705, "offsetInEndSection": 1803, "text": "the most important causes malignant pancreatic neuroendocrine tumors (NET) and thymic carcinoids. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435440", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "Multiple endocrine neoplasia type 1 (MEN1) is inherited in an autosomal dominant fashion and predisposes to the development of hyperplastic or neoplastic changes in the parathyroid and pituitary glands and the endocrine pancreas, along with numerous other characteristic tumors and features. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279763", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid and adrenocortical tumors, and neuroendocrine tumors (NETs) of the pancreas and pituitary. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024266", "endSection": "sections.0" }, { "offsetInBeginSection": 224, "offsetInEndSection": 362, "text": "The pancreatic NETs are predominantly gastrinomas and insulinomas, and the pituitary NETs are mostly prolactinomas and somatotrophinomas. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024266", "endSection": "sections.0" }, { "offsetInBeginSection": 461, "offsetInEndSection": 617, "text": "We address the potential role of miRNAs in the endocrine pancreas, the pituitary gland, and the parathyroid glands-areas where MEN 1 shows high penetrance. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21613051", "endSection": "sections.0" }, { "offsetInBeginSection": 749, "offsetInEndSection": 921, "text": "Moreover, studies have provided evidence that dysregulation of miRNAs was responsible for endocrine carcinogenesis, including pancreatic, pituitary, and parathyroid tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21613051", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "MEN1 and MEN2 are rare inherited cancer syndromes which express a variety of endocrine and nonendocrine tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21302639", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Multiple endocrine neoplasia Type 1 (MEN1) is a rare hereditary tumor syndrome predisposing to tumor development in several endocrine organs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20175448", "endSection": "sections.0" }, { "offsetInBeginSection": 141, "offsetInEndSection": 240, "text": " Its major manifestations include hyperparathyroidism, tumors of endocrine pancreas and pituitary. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20175448", "endSection": "sections.0" }, { "offsetInBeginSection": 241, "offsetInEndSection": 459, "text": "eside these three, several other endocrine (adrenocortical, foregut carcinoid) and nonendocrine (lipoma, angiofibroma, collagenoma, ependymoma, meningioma) tumors have been described to be associated with this syndrome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20175448", "endSection": "sections.0" }, { "offsetInBeginSection": 461, "offsetInEndSection": 764, "text": "Both familial and sporadic forms of the disease are known. The diagnosis of MEN1 can be established if two of the three major manifestations are found in the same patient, whereas the diagnosis of familial MEN1 requires one MEN1 patient and a first degree relative with at least one MEN1 manifestation. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20175448", "endSection": "sections.0" }, { "offsetInBeginSection": 875, "offsetInEndSection": 997, "text": "Both benign (parathyroid, anterior pituitary) and malignant (gastrinoma, glucagonoma) lesions may develop in MEN1 patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20175448", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Multiple endocrine neoplasia type 1 (MEN1) is a classic hereditary tumor syndrome characterized by a genetic predisposition to develop a variety of neuroendocrine neoplasias and hormone excess syndromes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11914929", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Multiple endocrine neoplasia type 1 (MEN 1) is a familial syndrome characterized by parathyroid, enteropancreatic and pituitary tumors. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664520", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumor syndrome characterized by the development of multiple endocrine tumors", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9820618", "endSection": "sections.0" }, { "offsetInBeginSection": 698, "offsetInEndSection": 1175, "text": "Multiple facial angiofibromas were observed in 28 (88%) of the patients with MEN1, with 16 patients (50%) having 5 or more. Angiofibromas were clinically and histologically identical to those in individuals with tuberous sclerosis. Collagenomas were observed in 23 patients (72%). Also observed were cafe au lait macules in 12 patients (38%), lipomas in 11 patients (34%), confetti-like hypopigmented macules in 2 patients (6%), and multiple gingival papules in 2 patients (6%)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9236523", "endSection": "sections.0" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1484, "text": "Multiple angiofibromas, collagenomas, lipomas, confetti-like hypopigmented macules and multiple gingival papules are cutaneous manifestations of MEN1 and should be looked for in both family members of patients with MEN1 and individuals with hyperparathyroidism of other MEN1-associated tumors. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9236523", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by nodular proliferation of the parathyroid glands and tumors of the anterior pituitary gland, the endocrine pancreas, and the neuroendocrine cell system of the gut.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7962349", "endSection": "sections.0" }, { "offsetInBeginSection": 400, "offsetInEndSection": 613, "text": "We report here a genetic study of a female MEN1 patient with the association of nodular hyperplasia of two parathyroid glands, an insulinoma, multiple duodenal gastrinomas, a prolactinoma, and a gastric carcinoid.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7962349", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 213, "text": "Multiple endocrine neoplasia type 1 (MEN1) is defined clinically by the combined occurrence of multiple tumors, typically of the parathyroid glands, pancreatic islet cells, and anterior pituitary gland.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18172277", "endSection": "sections.0" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1485, "text": "In support of previous findings in islet tumors, we found down-regulation of the cell-cycle regulator, p18, in both the pancreatic islet and pituitary adenomas, suggesting that reduced p18 levels may be important for Men1-related tumorigenesis in multiple tissues. Surprisingly, we identified increased p16 transcript in pancreatic islet and pituitary tumors. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17455252", "endSection": "sections.0" }, { "offsetInBeginSection": 163, "offsetInEndSection": 458, "text": " The patient was studied and diagnosed with a multiple endocrine neoplasia type I (MEN I), familiar (mother with MEN I). A scintigraphic study with 99mTc-MIBI was performed in order to localize hyperfunctioning parathyroid glands because of biochemical diagnosis of primary hyperparathyroidism. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10614532", "endSection": "sections.0" }, { "offsetInBeginSection": 761, "offsetInEndSection": 869, "text": "The tumor was removed and histologically confirmed as a carcinoid within a thymus in a MEN type I syndrome. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10614532", "endSection": "sections.0" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1040, "text": "MEN I patients can benefit from the examination with this agent which can potentially localize not only parathyroid endocrine pathology but also unknown associated tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10614532", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Pancreatic endocrine tumors occur sporadically and as part of the multiple endocrine neoplasia type 1 (MEN 1) and von Hippel-Lindau (VHL) syndromes. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502325", "endSection": "sections.0" }, { "offsetInBeginSection": 436, "offsetInEndSection": 701, "text": "We have analyzed 22 nonfamilial and 16 MEN 1-associated pancreatic endocrine tumors for loss of heterozygosity (LOH) at 3p, 11q13, and 18q. LOH at 3p was revealed in 45% and 36% of tumors from 31 patients with nonfamilial and MEN 1-associated disease, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502325", "endSection": "sections.0" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1670, "text": "The data indicate involvement of tumor suppressor genes on 3p and 18q, in addition to the MEN1 gene at 11q13, in the tumorigenesis of both nonfamilial and MEN 1-associated pancreatic endocrine tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502325", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Multiple endocrine neoplasia type 1 (MEN1) is characterized by the development of endocrine tumors of the parathyroid and pituitary glands, pancreas, and duodenum. Less frequently occurring tumors associated with MEN1 include non-endocrine tumors such as lipomas and angiofibromas. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10496602", "endSection": "sections.0" }, { "offsetInBeginSection": 282, "offsetInEndSection": 468, "text": "An increased incidence of thyroid neoplasms, leiomyomas, adrenal cortical hyperplasia, hepatic focal nodular hyperplasia, and renal angiomyolipoma has been noted in the MEN1 population. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10496602", "endSection": "sections.0" }, { "offsetInBeginSection": 768, "offsetInEndSection": 1055, "text": "A germline mutation of the MEN1 gene was detected, and deletions of the MEN1 gene were consistently detected in multiple neuroendocrine tumors involving the parathyroid glands and the pancreas and a hepatic neuroendocrine tumor metastasis, as predicted by Knudson's \"two hit\" hypothesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10496602", "endSection": "sections.0" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1232, "text": "Two hits of the MEN1 gene were also detected in esophageal leiomyoma tissue, suggesting that tumorigenesis was directly related to the patient's underlying MEN1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10496602", "endSection": "sections.0" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1612, "text": " In contrast, follicular thyroid adenoma, papillary thyroid carcinoma, hepatic focal nodular hyperplasia, and adrenal cortical hyperplasia consistently showed retained heterozygosity of the MEN1 gene with flanking markers and an intragenic marker. Therefore, these tumors appear to develop along pathogenetic pathways that are different from classical MEN1-associated tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10496602", "endSection": "sections.0" }, { "offsetInBeginSection": 312, "offsetInEndSection": 624, "text": "Twelve unrelated (German MEN1 families and their associated tumors (5 parathyroid tumors, 1 vipoma, 1 gastrinoma, 1 insulinoma) were characterized for MEN1 gene mutations by single-strand conformational variant (SSCV) analysis and DNA sequence analysis as well as for loss of heterozygosity on chromosome 11q13. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9820618", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Multiple endocrine neoplasia type 1 (MEN1) consists of benign, and sometimes malignant, tumors (often multiple in a tissue) of the parathyroids, enteropancreatic neuroendocrine system, anterior pituitary, and other tissues. Skin angiofibromas and skin collagenomas are common. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9735087", "endSection": "sections.0" } ] }, { "body": "Which is the protein implicated in Spinocerebellar ataxia type 3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20943656", "http://www.ncbi.nlm.nih.gov/pubmed/21827905", "http://www.ncbi.nlm.nih.gov/pubmed/24293103", "http://www.ncbi.nlm.nih.gov/pubmed/24272589", "http://www.ncbi.nlm.nih.gov/pubmed/9292723", "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "http://www.ncbi.nlm.nih.gov/pubmed/20865150", "http://www.ncbi.nlm.nih.gov/pubmed/16389311", "http://www.ncbi.nlm.nih.gov/pubmed/21653538", "http://www.ncbi.nlm.nih.gov/pubmed/23617879", "http://www.ncbi.nlm.nih.gov/pubmed/20007218", "http://www.ncbi.nlm.nih.gov/pubmed/24685680" ], "ideal_answer": [ "Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3).", "Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem" ], "exact_answer": [ "Ataxin-3" ], "type": "factoid", "id": "57138eb21174fb175500000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24272589", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 164, "text": "Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding ataxin-3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23617879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of the polyglutamine repeat region within the ataxin-3 protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20007218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Spinocerebellar ataxia type 3 is caused by a polyglutamine expansion in the ataxin-3 protein, resulting in gain of toxic function of the mutant protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 411, "text": "Here, we provide insight into the mechanism by which ubiquitination directly enhances the activity of ataxin-3, a DUb implicated in protein quality control and the disease protein in the polyglutamine neurodegenerative disorder, Spinocerebellar Ataxia Type 3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20943656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Ataxin-3, the disease protein in the neurodegenerative disorder Spinocerebellar Ataxia Type 3 or Machado Joseph disease, is a cysteine protease implicated in the ubiquitin proteasome pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20865150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Ataxin-3 (AT3) is the protein that triggers the inherited neurodegenerative disorder spinocerebellar ataxia type 3 when its polyglutamine (polyQ) stretch close to the C-terminus exceeds a critical length", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685680", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 383, "text": "Here, in studies of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 accumulates in ubiquitinated intranuclear inclusions selectively in neurons of affected brain regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9292723", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 724, "text": "This pathogenic repeat in MJD/SCA3 encodes an expanded tract of the amino acid glutamine in the disease protein, which is known as ataxin-3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21827905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Machado-Joseph disease (MJD), also called spinocerebellar ataxia type 3, is caused by mutant ataxin-3 with a polyglutamine expansion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16389311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": " Mutant ataxin-3 is aberrantly folded and proteolytically cleaved in spinocerebellar ataxia type 3. The C-terminal region of the protein includes a polyglutamine stretch that is expanded in spinocerebellar ataxia type 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21653538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of the polyglutamine repeat region within the ataxin-3 protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20007218", "endSection": "abstract" } ] }, { "body": "What is Tn-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21253457", "http://www.ncbi.nlm.nih.gov/pubmed/19767758", "http://www.ncbi.nlm.nih.gov/pubmed/25636611", "http://www.ncbi.nlm.nih.gov/pubmed/22925268", "http://www.ncbi.nlm.nih.gov/pubmed/24077707", "http://www.ncbi.nlm.nih.gov/pubmed/25139902", "http://www.ncbi.nlm.nih.gov/pubmed/23990803", "http://www.ncbi.nlm.nih.gov/pubmed/21053251" ], "ideal_answer": [ "The transposon mutagenesis and high-throughput sequencing (Tn-seq) is a technique that allows for quantitative assessment of individual mutants within a transposon mutant library by sequencing the transposon-genome junctions and then compiling mutant presence by mapping to a base genome. Using Tn-seq, it is possible to quickly define all the insertional mutants in a library and thus identify nonessential genes under the conditions in which the library was produced. Identification of fitness of individual mutants under specific conditions can be performed by exposing the library to selective pressures." ], "type": "summary", "id": "56d2ae19f22319765a000006", "snippets": [ { "offsetInBeginSection": 2357, "offsetInEndSection": 2536, "text": " Using Tn-seq, a genome-wide fitness profiling technique, we identified several functions required for fitness of Y.\u00a0pestis in vivo that were not previously known to be important.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25139902", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 927, "text": "Tn-seq is a technique that allows for quantitative assessment of individual mutants within a transposon mutant library by sequencing the transposon-genome junctions and then compiling mutant presence by mapping to a base genome. Using Tn-seq, it is possible to quickly define all the insertional mutants in a library and thus identify nonessential genes under the conditions in which the library was produced. Identification of fitness of individual mutants under specific conditions can be performed by exposing the library to selective pressures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Genome-wide fitness and genetic interactions determined by Tn-seq, a high-throughput massively parallel sequencing method for microorganisms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21053251", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Tn-seq: high-throughput parallel sequencing for fitness and genetic interaction studies in microorganisms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19767758", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 541, "text": "Here we present the method Tn-seq, with which it has become possible to quantitatively determine fitness for most genes in a microorganism and to screen for quantitative genetic interactions on a genome-wide scale and in a high-throughput fashion. Tn-seq can thus direct studies in the annotation of genes and untangle complex phenotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21053251", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 548, "text": "Here we present a method (Tn-seq) for accurately determining quantitative genetic interactions on a genome-wide scale in microorganisms. Tn-seq is based on the assembly of a saturated Mariner transposon insertion library. After library selection, changes in frequency of each insertion mutant are determined by sequencing the flanking regions en masse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19767758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Whole-genome fitness analysis in microbes that uses saturating transposon mutagenesis combined with massively parallel sequencing (Tn-seq) is providing a measure of the contribution of each gene to a given growth condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24077707", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 297, "text": "The procedure employs a new Tn-seq methodology based on the generation and amplification of single-strand circles carrying transposon junction sequences (the Tn-seq circle method),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21253457", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 417, "text": "Here we present a method (Tn-seq) for accurately determining quantitative genetic interactions on a genome-wide scale in microorganisms. Tn-seq is based on the assembly of a saturated Mariner transposon insertion library.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19767758", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 541, "text": "Here we present the method Tn-seq, with which it has become possible to quantitatively determine fitness for most genes in a microorganism and to screen for quantitative genetic interactions on a genome-wide scale and in a high-throughput fashion. Tn-seq can thus direct studies in the annotation of genes and untangle complex phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21053251", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 743, "text": "Tn-seq measures the frequency of actual members of a heterogeneous mutant pool undergoing purifying selection to determine the contribution of every non-essential gene in the genome to the fitness of an organism under a given condition. Here we use Tn-seq to assess gene function in the Gram negative \u03b3-proteobacterium Shewanella oneidensis strain MR-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22925268", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 918, "text": "Towards this goal, we utilized a quantitative genetic footprinting technique known as transposon insertion sequencing (Tn-seq) in conjunction with comparative pathogenomics to functionally dissect the genetic repertoire of a reference ExPEC isolate. Using Tn-seq and high-throughput zebrafish infection models, we tracked changes in the abundance of ExPEC variants within saturated transposon mutant libraries following selection within distinct host niches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990803", "endSection": "abstract" } ] }, { "body": "Is metabolic syndrome related with cardiovascular disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18945929", "http://www.ncbi.nlm.nih.gov/pubmed/24247648", "http://www.ncbi.nlm.nih.gov/pubmed/19196885", "http://www.ncbi.nlm.nih.gov/pubmed/24320036", "http://www.ncbi.nlm.nih.gov/pubmed/24320031", "http://www.ncbi.nlm.nih.gov/pubmed/24287796", "http://www.ncbi.nlm.nih.gov/pubmed/24328010", "http://www.ncbi.nlm.nih.gov/pubmed/21234418", "http://www.ncbi.nlm.nih.gov/pubmed/24320038", "http://www.ncbi.nlm.nih.gov/pubmed/24290090" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2041867", "o": "Syndrome, Metabolic Cardiovascular" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2029581", "o": "Cardiovascular Syndrome, Metabolic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2029582", "o": "Cardiovascular Syndromes, Metabolic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17989670", "o": "Metabolic Cardiovascular Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2035905", "o": "Metabolic Cardiovascular Syndrome" } ], "ideal_answer": [ "The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM)." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024821", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318", "http://www.disease-ontology.org/api/metadata/DOID:14221", "http://www.disease-ontology.org/api/metadata/DOID:1287" ], "type": "yesno", "id": "5328185dd6d3ac6a3400000e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 282, "text": "The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320038", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 622, "text": "As a molecular link between metabolic signals, inflammation, and vascular dysfunction, resistin can be proposed as playing a significant role in the heightened inflammatory state induced by metabolic stress linked to excessive caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type 2 diabetes (T2DM), and cardiovascular disease (CVD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320036", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "The metabolic syndrome (MetS) is associated with a higher risk for both, type 2 diabetes mellitus and cardiovascular disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320031", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 241, "text": "arotid intima-media thickness (CIMT) has been widely used as a surrogate marker of atherosclerosis and cardiovascular disease (CVD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24328010", "endSection": "abstract" } ] }, { "body": "Is there any functional association during viral replication between flaviviridae viral RNA depended RNA polymerase and viral helicase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23463199", "http://www.ncbi.nlm.nih.gov/pubmed/22040846", "http://www.ncbi.nlm.nih.gov/pubmed/17319152", "http://www.ncbi.nlm.nih.gov/pubmed/19951725", "http://www.ncbi.nlm.nih.gov/pubmed/21946389", "http://www.ncbi.nlm.nih.gov/pubmed/15917225", "http://www.ncbi.nlm.nih.gov/pubmed/17660525", "http://www.ncbi.nlm.nih.gov/pubmed/21898331", "http://www.ncbi.nlm.nih.gov/pubmed/23157297", "http://www.ncbi.nlm.nih.gov/pubmed/18179252" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C0206510", "o": "http://linkedlifedata.com/resource/umls/id/C0035691" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0206510", "o": "http://linkedlifedata.com/resource/umls/label/A0363752" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0206510", "o": "http://linkedlifedata.com/resource/umls/label/A0363753" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7573489", "o": "RNA Virus" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0112753", "o": "RNA Viruses" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0206510", "o": "http://linkedlifedata.com/resource/umls/label/A0363751" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0206510", "o": "http://linkedlifedata.com/resource/umls/label/A2143236" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0206510", "o": "http://linkedlifedata.com/resource/umls/label/A0363752" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0132798", "o": "Virus, RNA" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0363751", "o": "Flaviviridae" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7574474", "o": "Viruses, RNA" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0451316", "o": "RNA virus" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2143236", "o": "Flavivirus (arbovirus group B)" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7666306", "o": "Virus-RNA" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050303", "o": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:1886" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:1886", "o": "Flaviviridae infectious disease" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050303", "o": "Hepacivirus infectious disease" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:993", "o": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:1886" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:993", "o": "Flavivirus infectious disease" } ], "ideal_answer": [ "Several labs have obtained evidence for a protein complex that involves many of the nonstructural (NS) proteins encoded by the virus. NS3, NS4A, NS4B, NS5A, and NS5B appear to interact structurally and functionally. The interaction between the helicase, NS3, and the RNA polymerase, NS5B play a key role in viral replication. Pull-down experiments and surface plasmon resonance data indicate a direct interaction between NS3 and NS5B that is primarily mediated through the protease domain of NS3. This interaction reduces the basal ATPase activity of NS3. However, NS5B stimulates product formation in RNA unwinding experiments under conditions of excess nucleic acid substrate. When the concentrations of NS3 and NS5B are in excess of nucleic acid substrate, NS5B reduces the rate of NS3-catalyzed unwinding. Under pre-steady-state conditions, in which NS3 and substrate concentrations are similar, product formation increased in the presence of NS5B. The increase was consistent with 1:1 complex formed between the two proteins." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012194", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020365", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012367" ], "type": "yesno", "id": "5321b8579b2d7acc7e000008", "snippets": [ { "offsetInBeginSection": 275, "offsetInEndSection": 1527, "text": "Several labs have obtained evidence for a protein complex that involves many of the nonstructural (NS) proteins encoded by the virus. NS3, NS4A, NS4B, NS5A, and NS5B appear to interact structurally and functionally. In this study, we investigated the interaction between the helicase, NS3, and the RNA polymerase, NS5B. Pull-down experiments and surface plasmon resonance data indicate a direct interaction between NS3 and NS5B that is primarily mediated through the protease domain of NS3. This interaction reduces the basal ATPase activity of NS3. However, NS5B stimulates product formation in RNA unwinding experiments under conditions of excess nucleic acid substrate. When the concentrations of NS3 and NS5B are in excess of nucleic acid substrate, NS5B reduces the rate of NS3-catalyzed unwinding. Under pre-steady-state conditions, in which NS3 and substrate concentrations are similar, product formation increased in the presence of NS5B. The increase was consistent with 1:1 complex formed between the two proteins. A fluorescently labeled form of NS3 was used to investigate this interaction through fluorescence polarization binding assays. Results from this assay support interactions that include a 1:1 complex formed between NS3 and NS5B.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18179252", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 1037, "text": "Contradictory results have been reported regarding NS3 in RNA synthesis. To investigate the effect of NS3 on classical swine fever virus (CSFV) NS5B RNA-dependent RNA polymerase activity (RdRp) activity and NS3-NS5B interaction, RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses containing NS5B and either of NS3 protein and the different truncated NS3 mutants were performed, respectively. We found that NS3 stimulated NS5B RdRp activity in a dose-dependent manner by binding to NS5 through a NS3 protease domain. Furthermore, mapping important regions of the NS3 protease domain was carried out by deletion mutagenesis, associated with RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses. Results showed that stimulation of CSFV NS5B RdRp activity was obtained by NS3 binding to NS5B through a 31-amino acid fragment at the N-terminal end of NS3 protease domain, which mediated a specific NS3-NS5B interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19951725", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 474, "text": "The protocols detailed in this unit are used to purify three recombinant enzymes that are widely used in HCV research: the HCV NS3 protease domain, the helicase domain as an NS3+NS4A complex, and the NS5B RNA-dependent RNA polymerase. The active enzymes are purified to homogeneity by two-column chromatography to support a screening program for HCV inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21898331", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 945, "text": "Among potential targets are viral entry factors, including scavenger receptor type B1 (SR-B1) and CD81, as well as neutralizing antibodies against the viral glycoproteins. Popular targets related to translation and replication are the NS3/4A protease (inhibited by telaprevir and boceprevir) and the NS5B polymerase, as well as the NS2/3 autoprotease, the NS3 helicase, and nonenzymatic targets such as NS4B and NS5A proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21946389", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1501, "text": "The NS3 helicase domain competes with NS3 full-length for NS5 RdRp binding, with a K(d.) of 2.5\u03bcM. Since NS3 and NS5 are required for DENV replication, this fascile assay could be used to screen for non-nucleoside, allosteric inhibitors that disrupt the interaction between the two proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22040846", "endSection": "abstract" } ] }, { "body": "Are defects in recombination repair involved in carcinogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22276468", "http://www.ncbi.nlm.nih.gov/pubmed/11178982", "http://www.ncbi.nlm.nih.gov/pubmed/23541693", "http://www.ncbi.nlm.nih.gov/pubmed/21404276", "http://www.ncbi.nlm.nih.gov/pubmed/24051048", "http://www.ncbi.nlm.nih.gov/pubmed/23721719", "http://www.ncbi.nlm.nih.gov/pubmed/19083132", "http://www.ncbi.nlm.nih.gov/pubmed/17397816", "http://www.ncbi.nlm.nih.gov/pubmed/12865926", "http://www.ncbi.nlm.nih.gov/pubmed/12016139", "http://www.ncbi.nlm.nih.gov/pubmed/12592385", "http://www.ncbi.nlm.nih.gov/pubmed/17636314", "http://www.ncbi.nlm.nih.gov/pubmed/12427531", "http://www.ncbi.nlm.nih.gov/pubmed/12488587", "http://www.ncbi.nlm.nih.gov/pubmed/22798379", "http://www.ncbi.nlm.nih.gov/pubmed/21267443", "http://www.ncbi.nlm.nih.gov/pubmed/17363343", "http://www.ncbi.nlm.nih.gov/pubmed/22665067", "http://www.ncbi.nlm.nih.gov/pubmed/23675572", "http://www.ncbi.nlm.nih.gov/pubmed/12191483", "http://www.ncbi.nlm.nih.gov/pubmed/20298636", "http://www.ncbi.nlm.nih.gov/pubmed/10753787", "http://www.ncbi.nlm.nih.gov/pubmed/16258176", "http://www.ncbi.nlm.nih.gov/pubmed/24104500", "http://www.ncbi.nlm.nih.gov/pubmed/11395777", "http://www.ncbi.nlm.nih.gov/pubmed/23628323", "http://www.ncbi.nlm.nih.gov/pubmed/23620081", "http://www.ncbi.nlm.nih.gov/pubmed/16555998", "http://www.ncbi.nlm.nih.gov/pubmed/23125219", "http://www.ncbi.nlm.nih.gov/pubmed/15660524", "http://www.ncbi.nlm.nih.gov/pubmed/21427292" ], "triples": [ { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/9111189", "o": "Which DNA polymerases are used for DNA-repair in eukaryotes?" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/9111189", "o": "Carcinogenesis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/9111189", "o": "http://purl.uniprot.org/pubmed/9111189" }, { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/11062157", "o": "Identification of single nucleotide polymorphisms in human DNA repair genes." }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/11062157", "o": "Carcinogenesis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/11062157", "o": "http://purl.uniprot.org/pubmed/11062157" }, { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/12419828", "o": "Diet, cancer and aging in DNA mismatch repair deficient mice." }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/12419828", "o": "http://purl.uniprot.org/pubmed/12419828" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/12419828", "o": "Carcinogenesis" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/P18887", "o": "http://purl.uniprot.org/citations/10783319" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10783319", "o": "Carcinogenesis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10783319", "o": "http://purl.uniprot.org/medline/20247096" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10783319", "o": "http://purl.uniprot.org/pubmed/10783319" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5031383838370036", "o": "X-ray repair cross-complementing protein 1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5031383838370035", "o": "DNA repair protein XRCC1" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/10783319", "o": "http://purl.uniprot.org/pubmed/10783319" }, { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/10590213", "o": "Involvement of p53 in X-ray induced intrachromosomal recombination in mice." }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10590213", "o": "http://purl.uniprot.org/pubmed/10590213" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10590213", "o": "Carcinogenesis" } ], "ideal_answer": [ "Yes. The breast cancer-associated BRCA1 and BRCA2 proteins are strongly implicated in recombination repair.", "Carcinogenesis or oncogenesis or tumorigenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes at the cellular, genetic and epigenetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.\nCarcinogenesis is caused by mutation and epimutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. The uncontrolled and often rapid proliferation of cells can lead to benign tumors; some types of these may turn into malignant tumors (cancer). Based on studies, carcinogenesis also related with the defects in recombination repair." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005785", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000724", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059767", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059765", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006310", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036298", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063646", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011995", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006281", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000725", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051721" ], "type": "yesno", "id": "52f77f752059c6d71c00002b", "snippets": [ { "offsetInBeginSection": 295, "offsetInEndSection": 518, "text": "Inherited mutations in genes involved in HR are associated with gene rearrangement and may be a prerequisite for tumor development in some cancer-prone hereditary diseases like Bloom, Werner and Rothmund-Thomson syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22276468", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 312, "text": "Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24104500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "Although alcohol consumption is related to increased cancer risk, its molecular mechanism remains unclear. Here, we demonstrate that an intake of 10% alcohol for 4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde (AA), the first product of ethanol metabolism, is believed to be responsible for DNA damage induced by alcohol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23125219", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 447, "text": "Although efficiency of these repair processes substantially decrease the efficacy of cancer chemotherapies that target DNA, compromised DNA repair contributes to mutagenesis and genomic instability leading to carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16555998", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 82, "text": "damage response and repair pathways are important barriers to carcinogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23620081", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 542, "text": "olymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely documented. For colorectal cancer, the loss of mismatch repair gene activity is a key genetic determinant. Nucleotide excision repair (NER), recombination repair (RR) and base excision repair (BER) pathways have critical roles in protection against other cancers, and we wished to investigate their role in colorectal cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12865926", "endSection": "abstract" } ] }, { "body": "Which is the prevalence of cystic fibrosis in the human population?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15970608", "http://www.ncbi.nlm.nih.gov/pubmed/11336401", "http://www.ncbi.nlm.nih.gov/pubmed/18442953", "http://www.ncbi.nlm.nih.gov/pubmed/15266396", "http://www.ncbi.nlm.nih.gov/pubmed/22627569", "http://www.ncbi.nlm.nih.gov/pubmed/18243066" ], "ideal_answer": [ "Prevalence of Cystic Fibrosis varies according to the population. A theoretical estimate of the prevalence of cystic fibrosis based on anthropological data suggested a frequency of 25 affected individuals/100,000 inhabitants. However, real data indicated that the true prevalence in the population was considerably lower (6.9 cases/100,000 inhabitants). Results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98.", "The results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98 (PMID: 18442953) The allelic frequency of this variant was calculated to be 0.7% for this population (PMID: 22627569) CF mutations were identified in 374 (4.0%) individuals. (PMID: 11336401)" ], "exact_answer": [ "0.7\u20137/100000 inhabitants" ], "concepts": [ "http://www.uniprot.org/uniprot/CFTR_MACMU", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003550", "http://www.disease-ontology.org/api/metadata/DOID:2975", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005355", "http://www.disease-ontology.org/api/metadata/DOID:1485", "http://www.disease-ontology.org/api/metadata/DOID:10353", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015995" ], "type": "factoid", "id": "513ce5f2bee46bd34c00000a", "snippets": [ { "offsetInBeginSection": 688, "offsetInEndSection": 771, "text": "The allelic frequency of this variant was calculated to be 0.7% for this population", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627569", "endSection": "sections.0" }, { "offsetInBeginSection": 111, "offsetInEndSection": 365, "text": "The results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18442953", "endSection": "sections.0" }, { "offsetInBeginSection": 741, "offsetInEndSection": 942, "text": "The age related prevalence of CF among the South Asian and general populations was: 0-14 years, 1:9200 versus 1:6600; 15-24 years, 1:13,200 versus 1:7600; older than 25 years, 1:56,600 versus 1:12,400.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15970608", "endSection": "sections.0" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1130, "text": "A theoretical estimate of the prevalence of cystic fibrosis based on anthropological data suggested a frequency of 25 affected individuals/100,000 inhabitants. However, our data indicated that the true prevalence in the population was considerably lower (6.9 cases/100,000 inhabitants)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15266396", "endSection": "sections.0" }, { "offsetInBeginSection": 856, "offsetInEndSection": 911, "text": "CF mutations were identified in 374 (4.0%) individuals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336401", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The aim of this study was to evaluate the screening policies of cystic fibrosis (CF) in the Jewish population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336401", "endSection": "sections.0" } ] }, { "body": "Are seizures among the neurological symptoms of incontinentia pigmenti?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22564885", "http://www.ncbi.nlm.nih.gov/pubmed/15127315", "http://www.ncbi.nlm.nih.gov/pubmed/24682289", "http://www.ncbi.nlm.nih.gov/pubmed/13679126", "http://www.ncbi.nlm.nih.gov/pubmed/12437562", "http://www.ncbi.nlm.nih.gov/pubmed/23622185", "http://www.ncbi.nlm.nih.gov/pubmed/25238668", "http://www.ncbi.nlm.nih.gov/pubmed/17990592" ], "ideal_answer": [ "Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth." ], "exact_answer": "yes", "type": "yesno", "id": "5721f6f90fd6f91b68000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "High-dose glucocorticoid therapy in the management of seizures in neonatal incontinentia pigmenti", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682289", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682289", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 189, "text": "Some children with incontinentia pigmenti exhibit encephalopathic features with severe seizures and disturbed consciousness, from the neonatal through the early infantile period", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25238668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 808, "text": "Incontinentia pigmenti (IP) is a rare X-linked dominant neurocutaneous disorder affecting ectodermal tissue: skin, eyes, central nervous system, hair, nails, and teeth. It is usually lethal for males in utero. The involved gene is NEMO, an essential component of the nuclear factor-kappa B (NF-\u03baB) signaling pathway. Skin lesions are highly diagnostic, occurring in neonates, with a particular distribution on Blaschko lines. The severity of the disease is related to ocular and neurological impairment. The hallmark of ocular IP is retinal vasculopathy including peripheral retinal vascular nonperfusion, macular infarction and neovascularization, and preretinal neovascularization. CNS involvement consists of seizures, mental retardation, hemiparesis, spasticity, microcephaly, cerebellar ataxia, and coma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23622185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 525, "text": "Incontinentia Pigmenti is a rare X-linked multisystem disorder with well described and pathognomonic skin manifestations. Neurological manifestations are found in 30% of IP patients, forming one of the major causes of morbidity and mortality of the condition. In this review, clinical and brain imaging data of 45 IP patients with a neurological phenotype are reviewed. Several clinical presentations could be identified, comprising seizures, infantile encephalopathy, acute disseminated encephalomyelitis and ischemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22564885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Incontinentia pigmenti presenting as seizures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12437562", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Neonatal seizures in two sisters with incontinentia pigmenti.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15127315", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "High-dose glucocorticoid therapy in the management of seizures in neonatal incontinentia pigmenti: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682289", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Incontinentia Pigmenti is an X-linked dominant neurocutaneous disorder with central nervous system manifestations in 30% of cases, including seizures and mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/13679126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Neonatal seizures in two sisters with incontinentia pigmenti", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15127315", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "A rare cause of neonatal seizure: incontinentia pigmenti.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17990592", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Here, we describe the clinical, electrographic, and neuroradiologic effect of systemic glucocorticoid therapy in a neonate with incontinentia pigmenti manifesting an epileptic encephalopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Incontinentia pigmenti presenting as seizures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12437562", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Neonatal seizures in two sisters with incontinentia pigmenti.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15127315", "endSection": "title" } ] }, { "body": "Which are the different homologs or family members of the hedgehog proteins in mammals?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20519495", "http://www.ncbi.nlm.nih.gov/pubmed/22391297", "http://www.ncbi.nlm.nih.gov/pubmed/21167467", "http://www.ncbi.nlm.nih.gov/pubmed/12967338", "http://www.ncbi.nlm.nih.gov/pubmed/15645142", "http://www.ncbi.nlm.nih.gov/pubmed/18612197", "http://www.ncbi.nlm.nih.gov/pubmed/11044404" ], "ideal_answer": [ "Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic hedgehog (Shh), Indian hedgehog (Ihh) , and Desert hedgehog (Dhh), are present in mammals." ], "exact_answer": [ [ "Sonic hedgehog", "SHH" ], [ "Indian hedgehog", "IHH" ], [ "Desert hedgehog", "DHH" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053823", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005190", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097108" ], "type": "list", "id": "5524562387ecba3764000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20519495", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1261, "text": " We report here biochemical and x-ray structural studies of Sonic, Indian, and Desert Hh proteins both alone and complexed with active domains of CDO and BOC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20519495", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 580, "text": "Previous work has shown that activin, a TGF(beta+) signaling molecule, permits pancreas development by repressing expression of Sonic hedgehog (Shh), a member of the hedgehog family of signaling molecules that antagonize pancreas development. Here we show that Indian hedgehog (Ihh), another hedgehog family member, and Patched 1 (Ptc1), a receptor and negative regulator of hedgehog activity, are expressed in pancreatic tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11044404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "The original hedgehog (hh) gene was found in Drosophila and named for the appearance of a mutant phenotype which causes an embryo to be covered with pointy denticles, thus resembling a hedgehog. The hedgehog family consists of sonic hedgehog (Shh), desert hedgehog (Dhh), and Indian hedgehog (Ihh). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22391297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21167467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Hedgehog (Hh) plays a pivotal role in various tissues during embryonic development, tissue homeostasis and tumorigenesis. In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18612197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Sonic hedgehog (SHH), Desert hedgehog (DHH) and Indian hedgehog (IHH) bind to Patched family receptors (PTCH1 and PTCH2) to transduce signals to GLI1, GLI2 and GLI3. GLI family transcription factors then activate transcription of Hedgehog target genes, such as FOXE1 and FOXM1 encoding Forkhead-box transcription factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15645142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Indian hedgehog (IHH) and its receptors patched (PTC) and smoothened (SMO) belong to the hedgehog family of signaling molecules, which are essential for a variety of patterning events during mammalian tIssue development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12967338", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 232, "text": "In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18612197", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 233, "text": "In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18612197", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 272, "text": "A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20519495", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 271, "text": "A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20519495", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 232, "text": "In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18612197", "endSection": "abstract" } ] }, { "body": "What does mTOR stands for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24311635", "http://www.ncbi.nlm.nih.gov/pubmed/24309100", "http://www.ncbi.nlm.nih.gov/pubmed/24276258", "http://www.ncbi.nlm.nih.gov/pubmed/24290217", "http://www.ncbi.nlm.nih.gov/pubmed/24312355", "http://www.ncbi.nlm.nih.gov/pubmed/24307346", "http://www.ncbi.nlm.nih.gov/pubmed/24312415", "http://www.ncbi.nlm.nih.gov/pubmed/24289602", "http://www.ncbi.nlm.nih.gov/pubmed/24287118", "http://www.ncbi.nlm.nih.gov/pubmed/24270265", "http://www.ncbi.nlm.nih.gov/pubmed/24295418" ], "ideal_answer": [ "mTOR stands for: mammalian target of rapamycin." ], "exact_answer": [ "mammalian target of rapamycin" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058570", "http://www.uniprot.org/uniprot/MTOR_RAT" ], "type": "factoid", "id": "5505a587f73303d458000005", "snippets": [ { "offsetInBeginSection": 141, "offsetInEndSection": 178, "text": " mammalian target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24312415", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 318, "text": "mammalian target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24312355", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 52, "text": "mammalian target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311635", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 110, "text": "mammalian target or rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309100", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 131, "text": "mammalian target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24307346", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 568, "text": "mammalian target of rapamycin (mTOR) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24290217", "endSection": "abstract" }, { "offsetInBeginSection": 45, "offsetInEndSection": 82, "text": " mammalian target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295418", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 111, "text": " mammal target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289602", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 639, "text": " mammalian target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24287118", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 476, "text": "mammalian Target of Rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276258", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 342, "text": " mammalian target of rapamycin (mTOR) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24270265", "endSection": "abstract" } ] }, { "body": "Which is the most common genetic lesion among patients with Joubert Syndrome and a cerebello-oculo-renal phenotype?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24946806" ], "ideal_answer": [ "Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.", "Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion" ], "type": "summary", "id": "5722027a0fd6f91b68000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946806", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 547, "text": "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946806", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 421, "text": "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946806", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 423, "text": "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946806", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 423, "text": "Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946806", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 554, "text": "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. We present a Cep290 gene trap mouse model of JBTS that displays the kidney, eye, and brain abnormalities that define the syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946806", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 423, "text": "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946806", "endSection": "abstract" } ] }, { "body": "Which scales are recommended by the American Heart Association for depression screening in cardiovascular patients? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23283084", "http://www.ncbi.nlm.nih.gov/pubmed/19840561", "http://www.ncbi.nlm.nih.gov/pubmed/18824640", "http://www.ncbi.nlm.nih.gov/pubmed/21862720", "http://www.ncbi.nlm.nih.gov/pubmed/20435186", "http://www.ncbi.nlm.nih.gov/pubmed/19261139", "http://www.ncbi.nlm.nih.gov/pubmed/21505152" ], "ideal_answer": [ "Patient Health Questionnaire-2 (PHQ-2) and Patient Health Questionnaire-9 (PHQ-9) are recommended by the American Heart Association for depression screening in cardiovascular patients." ], "exact_answer": [ [ "patient health questionnaire-2" ], [ "patient health questionnaire-9" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000572", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008403" ], "type": "list", "id": "51486f7dd24251bc0500002e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 274, "text": "In 2008, the American Heart Association (AHA) recommended a 2-step screening method, consisting of the 2-item Patient Health Questionnaire (PHQ-2) followed by the 9-item Patient Health Questionnaire (PHQ-9), for identifying depression in cardiovascular patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862720", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 207, "text": "The American Heart Association (AHA) statement has recommended routine screening for depression in coronary artery disease with a 2-stage implementation of the Patient Health Questionnaire (PHQ).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505152", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 309, "text": "A recent American Heart Association (AHA) Prevention Committee report recommended depression screening of all coronary heart disease patients using 2- and 9-item instruments from the Patient Health Questionnaire (PHQ-2 and PHQ-9) to identify patients who may need further assessment and treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435186", "endSection": "sections.0" }, { "offsetInBeginSection": 348, "offsetInEndSection": 572, "text": "Patients were screened for depression using a protocol identical to the one endorsed by the AHA in a cardiology community clinic in Elmhurst (Queens, New York). Depression was assessed using the Patient Health Questionnaire.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19840561", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 467, "text": "Depression screening in cardiac patients has been recommended by the American Heart Association, but the best approach remains unclear. OBJECTIVE: To evaluate nurse-administered versions of the Patient Health Questionnaire for depression screening in patients hospitalized for acute coronary syndrome. METHODS: Staff nurses in an urban cardiac care unit administered versions 2, 9, and 10 of the questionnaire to 100 patients with acute coronary syndrome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23283084", "endSection": "sections.0" } ] }, { "body": "Is there a genome-wide technique for the detection of R-loop formation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24164596", "http://www.ncbi.nlm.nih.gov/pubmed/23868195", "http://www.ncbi.nlm.nih.gov/pubmed/25699710", "http://www.ncbi.nlm.nih.gov/pubmed/24636987", "http://www.ncbi.nlm.nih.gov/pubmed/23251031", "http://www.ncbi.nlm.nih.gov/pubmed/22279048" ], "ideal_answer": [ "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops. Here we show that recombination factors are required for the survival of yeast FACT mutants, consistent with an accumulation of DNA breaks that we detected by Rad52 foci and transcription-dependent hyperrecombination. The latter pathway operates on nascent transcripts that are not simultaneously translated and requires factors Rho, NusG, and NusA, each of which is essential for viability of WT Escherichia coli. DNA replication in Escherichia coli is normally initiated at a single origin, oriC, dependent on initiation protein DnaA.", "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops\nA bisulfite-sensitivity assay may demonstrate genome-wide increase in the occurrence of RNA-DNA hybrids (R-loops)." ], "exact_answer": "yes", "type": "yesno", "id": "56c332a350c68dd41600000d", "snippets": [ { "offsetInBeginSection": 448, "offsetInEndSection": 677, "text": "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22279048", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 717, "text": "We have used a bisulfite-sensitivity assay to demonstrate genome-wide increase in the occurrence of RNA-DNA hybrids (R-loops), including from antisense and read-through transcripts, in a nusG missense mutant defective for Rho-dependent termination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23251031", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1236, "text": "The results demonstrate a key function of FACT in the resolution of R-loop-mediated transcription-replication conflicts, likely associated with a specific chromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24636987", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 300, "text": "Previous work revealed that GC skew and R-loop formation associate with a core set of unmethylated CpG island (CGI) promoters in the human genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868195", "endSection": "abstract" } ] }, { "body": "How is CBX1/M31 related to position-effect variegation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10779362", "http://www.ncbi.nlm.nih.gov/pubmed/10671371", "http://www.ncbi.nlm.nih.gov/pubmed/10202156", "http://www.ncbi.nlm.nih.gov/pubmed/10516442", "http://www.ncbi.nlm.nih.gov/pubmed/1543904", "http://www.ncbi.nlm.nih.gov/pubmed/10581035" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2350241", "o": "http://linkedlifedata.com/resource/umls/id/C2350240" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2350240", "o": "http://linkedlifedata.com/resource/umls/label/A15579257" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2350241", "o": "http://linkedlifedata.com/resource/umls/label/A15579258" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2350241", "o": "http://linkedlifedata.com/resource/umls/label/A15579258" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2350240", "o": "http://linkedlifedata.com/resource/umls/label/A15585170" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15579258", "o": "Position Effect Variegation" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15583201", "o": "Position Effect, Chromosomal" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15579257", "o": "Chromosomal Position Effects" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2350240", "o": "http://linkedlifedata.com/resource/umls/label/A15585171" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2350240", "o": "http://linkedlifedata.com/resource/umls/label/A15579257" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15585171", "o": "Chromosomal Position Effect" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2350240", "o": "http://linkedlifedata.com/resource/umls/label/A15583201" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15585170", "o": "Position Effects, Chromosomal" } ], "ideal_answer": [ "M31 is a heterochromatin component, that is concentrated in the XY body during spermatogenesis. M31 overexpression has two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric." ], "concepts": [ "http://www.uniprot.org/uniprot/CBX1_HUMAN", "http://www.uniprot.org/uniprot/CBX1_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055012", "http://www.uniprot.org/uniprot/HXC8_MOUSE", "http://www.biosemantics.org/jochem#4262550" ], "type": "summary", "id": "530d7e8a38c1322806000001", "snippets": [ { "offsetInBeginSection": 476, "offsetInEndSection": 650, "text": "First, forced expression of full-length SUV39H1 (412 amino acids) redistributes endogenous M31 (HP1beta) and induces abundant associations with inter- and metaphase chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10779362", "endSection": "abstract" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1669, "text": "Together, our data reveal a dominant role(s) for the SET domain of SUV39H1 in the distribution of prominent heterochromatic proteins and suggest a possible link between a chromosomal SU(VAR) protein and histone H3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10779362", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 535, "text": "Using this motif, termed chromo box, we have cloned a mouse candidate modifier gene, M31, that also shows considerable sequence homology to Drosophila HP1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1543904", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 775, "text": "Here we report evidence of at least four independently segregating loci in the mouse homologous to the M31 cDNA. One of these loci--Cbx-rs1--maps to the X Chromosome (Chr), 1 cM proximal to Amg and outside the X-inactivation center region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1543904", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 905, "text": "Although there is significant heterochromatic overlap between SUV39H1 and M31 (HP1(beta)) during interphase, mitotic SUV39H1 displays a more restricted spatial and temporal association pattern with metaphase chromosomes than M31 (HP1(beta)), or the related HP1(&agr;) gene product", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10671371", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 165, "text": "which complex with the heterochromatin component M31.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10202156", "endSection": "title" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1097, "text": "In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10202156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "M31, a murine homolog of Drosophila HP1, is concentrated in the XY body during spermatogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10516442", "endSection": "title" }, { "offsetInBeginSection": 328, "offsetInEndSection": 530, "text": "The HP1 class of chromobox genes are thought to encode proteins involved in the packaging of chromosomal DNA into repressive heterochromatin domains, as seen, for example, in position-effect variegation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10516442", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 780, "text": "Study of the distribution of a murine HP1-like chromodomain protein, M31, during spermatogenesis revealed spreading from the tip of the XY body in mid-stage pachytene spermatocytes to include the whole of the XY body in late-pachytene spermatocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10516442", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 958, "text": "We also demonstrate that the formation of the XY body during spermatogenic progression in neonatal mice coincides with the expression of a novel nuclear isoform of M31, M31(p21", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10516442", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 897, "text": "Furthermore, by overexpressing a mammalian homologue (M31) of Drosophila melanogaster heterochromatin protein 1 (HP1; refs 7,8) in transgenic mouse lines that exhibit PEV, it is possible to modify the proportion of cells that silence the transgene in a dose-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581035", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1165, "text": "Thus, we show M31 overexpression to have two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581035", "endSection": "abstract" } ] }, { "body": "Can bioprinting use human cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25130390", "http://www.ncbi.nlm.nih.gov/pubmed/23197691", "http://www.ncbi.nlm.nih.gov/pubmed/20811115", "http://www.ncbi.nlm.nih.gov/pubmed/25242654", "http://www.ncbi.nlm.nih.gov/pubmed/21504055", "http://www.ncbi.nlm.nih.gov/pubmed/25047630", "http://www.ncbi.nlm.nih.gov/pubmed/25457969", "http://www.ncbi.nlm.nih.gov/pubmed/22436025", "http://www.ncbi.nlm.nih.gov/pubmed/24695367", "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "http://www.ncbi.nlm.nih.gov/pubmed/24157694", "http://www.ncbi.nlm.nih.gov/pubmed/24334142", "http://www.ncbi.nlm.nih.gov/pubmed/24188635", "http://www.ncbi.nlm.nih.gov/pubmed/25384685", "http://www.ncbi.nlm.nih.gov/pubmed/23380571", "http://www.ncbi.nlm.nih.gov/pubmed/23719889", "http://www.ncbi.nlm.nih.gov/pubmed/24439284", "http://www.ncbi.nlm.nih.gov/pubmed/22508498", "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "http://www.ncbi.nlm.nih.gov/pubmed/22767299", "http://www.ncbi.nlm.nih.gov/pubmed/23260439", "http://www.ncbi.nlm.nih.gov/pubmed/23575660", "http://www.ncbi.nlm.nih.gov/pubmed/24961492", "http://www.ncbi.nlm.nih.gov/pubmed/24903714", "http://www.ncbi.nlm.nih.gov/pubmed/23562089", "http://www.ncbi.nlm.nih.gov/pubmed/23015540", "http://www.ncbi.nlm.nih.gov/pubmed/20353253", "http://www.ncbi.nlm.nih.gov/pubmed/22394017", "http://www.ncbi.nlm.nih.gov/pubmed/21527813", "http://www.ncbi.nlm.nih.gov/pubmed/24758832", "http://www.ncbi.nlm.nih.gov/pubmed/24998183", "http://www.ncbi.nlm.nih.gov/pubmed/24887553", "http://www.ncbi.nlm.nih.gov/pubmed/23184715", "http://www.ncbi.nlm.nih.gov/pubmed/20546891", "http://www.ncbi.nlm.nih.gov/pubmed/25048797", "http://www.ncbi.nlm.nih.gov/pubmed/21358040" ], "ideal_answer": [ "Yes, human cells can be used for bioprinting" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062028", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ], "type": "yesno", "id": "571394141174fb175500000b", "snippets": [ { "offsetInBeginSection": 152, "offsetInEndSection": 273, "text": "In this study, human adipose-derived stem cells (hASCs) were printed in a free-scalable 3D grid pattern by means of LaBP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358040", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 777, "text": " Additionally, we provide the proof that even pre-differentiated hASCs could be utilized for the generation of 3D tissue grafts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1131, "text": "In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24334142", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 370, "text": "Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24695367", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 996, "text": "Bioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811115", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1303, "text": "3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "[Three dimensional bioprinting technology of human dental pulp cells mixtures].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 539, "text": "Here we report the development of clinically relevant sized tissue analogs by 3-D bioprinting, delivering human nasal inferior turbinate tissue-derived mesenchymal progenitor cells encapsulated in silk fibroin-gelatin (SF-G) bioink", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Sodium alginate hydrogel, stabilized with gelatin, is a suitable, biologically inert matrix that can be used for encapsulating and 3D bioprinting of bone-related SaOS-2 cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25047630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25130390", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "OBJECTIVE: To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Cellular behavior in micropatterned hydrogels by bioprinting system depended on the cell types and cellular interaction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23562089", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Engineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25047630", "endSection": "title" }, { "offsetInBeginSection": 823, "offsetInEndSection": 961, "text": "At the same time, the principal feasibility of bioprinting vascularized human organs as well as in vivo bioprinting has been demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811115", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1095, "text": "The bioprinting of complex 3D human tissues and constructs in vitro and especially in vivo are exciting, but long-term, applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811115", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 694, "text": "Bioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811115", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1581, "text": "In this study, the 3D bioprinting of hDPCs mixtures was realized, thus laying initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 861, "text": "Furthermore, it is not known how human valve cells respond to these printed environments. In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24334142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "[Three dimensional bioprinting technology of human dental pulp cells mixtures].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "endSection": "title" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1096, "text": "The bioprinting of complex 3D human tissues and constructs in vitro and especially in vivo are exciting, but long-term, applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24334142", "endSection": "title" }, { "offsetInBeginSection": 496, "offsetInEndSection": 585, "text": "Furthermore, it is not known how human valve cells respond to these printed environments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24334142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Engineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25047630", "endSection": "title" } ] }, { "body": "Is transcription-associated mutagenesis (TAM) related to gene expression levels?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23146897", "http://www.ncbi.nlm.nih.gov/pubmed/21177427", "http://www.ncbi.nlm.nih.gov/pubmed/21177431", "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "http://www.ncbi.nlm.nih.gov/pubmed/23055242", "http://www.ncbi.nlm.nih.gov/pubmed/10628973", "http://www.ncbi.nlm.nih.gov/pubmed/23564176", "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "http://www.ncbi.nlm.nih.gov/pubmed/15143174" ], "ideal_answer": [ "Spontaneous point mutation rate in a gene increases with its transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es). This phenomenon is termed transcription-associated mutation (TAM). Transcription-associated mutagenesis is directly proportional to the level of gene expression." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006351" ], "type": "yesno", "id": "5544f3005beec11c10000008", "snippets": [ { "offsetInBeginSection": 963, "offsetInEndSection": 1133, "text": "These mutations were frequent in plasmid-borne lacS expressed at a high level but not in single-copy lacS in the chromosome or at lower levels of expression in a plasmid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564176", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1683, "text": "The results suggest that important DNA repair or replication fidelity functions are impaired or overwhelmed in pJlacS, with results analogous to those of the \"transcription-associated mutagenesis\" seen in bacteria and eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564176", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 531, "text": "the rate of point mutation in a gene increases with the expression level of the gene. Transcription induces mutagenesis on both DNA strands, indicating simultaneous actions of several TAM mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "High-levels of transcription through a gene stimulate spontaneous mutation rate, a phenomenon termed transcription-associated mutation (TAM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a pGAL-CAN1 forward mutation assay for studying transcription-associated mutagenesis (TAM) in yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177427", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 514, "text": "The acquisition of mutations was directly correlated to the level of transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 976, "text": "Our results demonstrate that the level of Leu(+) reversions increased significantly in parallel with the induced increase in transcription levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "endSection": "title" }, { "offsetInBeginSection": 403, "offsetInEndSection": 577, "text": "spontaneous mutation rate is directly proportional to the transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "High transcription is associated with genetic instability, notably increased spontaneous mutation rates, which is a phenomenon termed Transcription-Associated-Mutagenesis (TAM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177431", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 856, "text": "Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177427", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 859, "text": "Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 416, "text": "Using comparative genomics of related species as well as mutation accumulation lines, we show in yeast that the rate of point mutation in a gene increases with the expression level of the gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "High transcription is associated with genetic instability, notably increased spontaneous mutation rates, which is a phenomenon termed Transcription-Associated-Mutagenesis (TAM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177431", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 858, "text": "Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "High-levels of transcription through a gene stimulate spontaneous mutation rate, a phenomenon termed transcription-associated mutation (TAM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055242", "endSection": "abstract" } ] }, { "body": "Is there a pharmacogenetic test for trastuzumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20590449", "http://www.ncbi.nlm.nih.gov/pubmed/16809727", "http://www.ncbi.nlm.nih.gov/pubmed/11838648", "http://www.ncbi.nlm.nih.gov/pubmed/17785760", "http://www.ncbi.nlm.nih.gov/pubmed/11265171", "http://www.ncbi.nlm.nih.gov/pubmed/15970231", "http://www.ncbi.nlm.nih.gov/pubmed/16235569", "http://www.ncbi.nlm.nih.gov/pubmed/15217485", "http://www.ncbi.nlm.nih.gov/pubmed/15510616", "http://www.ncbi.nlm.nih.gov/pubmed/21632460", "http://www.ncbi.nlm.nih.gov/pubmed/17159499", "http://www.ncbi.nlm.nih.gov/pubmed/17947471", "http://www.ncbi.nlm.nih.gov/pubmed/17184417", "http://www.ncbi.nlm.nih.gov/pubmed/11579337", "http://www.ncbi.nlm.nih.gov/pubmed/11097337", "http://www.ncbi.nlm.nih.gov/pubmed/22112244", "http://www.ncbi.nlm.nih.gov/pubmed/22461093", "http://www.ncbi.nlm.nih.gov/pubmed/22065003" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10771788", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1545807", "o": "trastuzumab" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0728747", "o": "http://linkedlifedata.com/resource/umls/label/A10771788" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A8438296", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16756458", "o": "TRASTUZUMAB" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00072", "o": "http://dbpedia.org/resource/Trastuzumab" } ], "ideal_answer": [ "Yes. HER2 testing is performed in breast cancer patients to determine suitability for trastuzumab (Herceptin therapy)." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4002084", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010597" ], "type": "yesno", "id": "514a1469d24251bc05000056", "snippets": [ { "offsetInBeginSection": 302, "offsetInEndSection": 518, "text": "The clinical need for novel approaches to improve drug therapy derives from the high rate of adverse reactions to drugs and their lack of efficacy in many individuals that may be predicted by pharmacogenetic testing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461093", "endSection": "sections.0" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1549, "text": "the assessment of the human epidermal growth factor receptor (HER-2) expression for trastuzumab therapy of breast cancer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461093", "endSection": "sections.0" }, { "offsetInBeginSection": 379, "offsetInEndSection": 440, "text": "HER2 positive breast cancer and the use of the drug Herceptin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17184417", "endSection": "sections.0" }, { "offsetInBeginSection": 696, "offsetInEndSection": 988, "text": "The dependence on gene copy number or expression levels of HER2 and epidermal growth factor receptor (EGFR) for therapeutic efficacy of trastuzumab and cetuximab (Erbitux), respectively, supports the importance of selecting suitable patient populations based on their pharmacogenetic profile.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16235569", "endSection": "sections.0" }, { "offsetInBeginSection": 289, "offsetInEndSection": 718, "text": "to explore informed consent issues surrounding the use of the drug Herceptin, widely cited as an example of a novel approach to drug development called pharmacogenetics. Drawing on qualitative semi-structured interviews with 25 UK-based breast cancer specialists, this paper explores Herceptin's disputed epistemological status, as an example of pharmacogenetics or as something out of the ordinary in terms of clinical practice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15970231", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in breast cancer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22065003", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Trastuzumab is standard of care in the treatment of human epidermal growth factor receptor (HER)-2\u207a early and advanced breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21632460", "endSection": "sections.0" }, { "offsetInBeginSection": 107, "offsetInEndSection": 169, "text": "HER-2 overexpression as a predictor of response to trastuzumab", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17947471", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Pharmacogenomic analysis aspires to identify individuals with specific genetic characteristics in order to predict a positive response or reduce a negative response to a therapeutic modality.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11097337", "endSection": "sections.0" }, { "offsetInBeginSection": 792, "offsetInEndSection": 998, "text": "Assays are available to detect the HER2 protein receptor or copies of the HER2 gene sequence to determine eligibility for Herceptin treatment or adriamycin treatment in node positive patients, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11097337", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Determining the HER2 status of breast carcinomas is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin), which has recently been licensed for the treatment of metastatic disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11265171", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 190, "text": "Laboratory testing of HER2/neu in breast carcinoma has become vital to patient care following the approval of trastuzumab as the first therapy to target the HER2/neu oncoprotein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11579337", "endSection": "sections.0" }, { "offsetInBeginSection": 337, "offsetInEndSection": 474, "text": "Immunohistochemical (IHC) analysis was performed with use of a diagnostic test for the assessment of HER2 overexpression, the HercepTest.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11838648", "endSection": "sections.0" }, { "offsetInBeginSection": 270, "offsetInEndSection": 490, "text": "To test for HER-2/neu overexpression in patients with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal anti-HER-2/neu antibody trastuzumab (Herceptin) in the treatment of non-Hodgkin's lymphoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15510616", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 195, "text": "To evaluate concordance between local and central laboratory HER2 testing results in patients from the North Central Cancer Treatment Group (NCCTG) N9831 adjuvant trial of trastuzumab.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16809727", "endSection": "sections.0" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1749, "text": "These findings support the importance of using high-volume, experienced laboratories for HER2 testing to improve the process of selecting patients likely to benefit from trastuzumab therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16809727", "endSection": "sections.0" }, { "offsetInBeginSection": 256, "offsetInEndSection": 617, "text": "we measured trastuzumab levels in the serum and in cerebrospinal fluid of metastatic breast cancer patients with brain metastases receiving trastuzumab for HER2-overexpressing metastatic breast cancer. In a pilot study, metastatic breast cancer patients with brain metastases and HER2-overexpressing tumors (HercepTest; Dako, Copenhagen, Denmark) were included.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17159499", "endSection": "sections.0" }, { "offsetInBeginSection": 1687, "offsetInEndSection": 1966, "text": "Monitoring of trastuzumab levels in the serum and cerebrospinal fluid may enable individualized therapy strategies in metastatic breast cancer patients with brain metastases, and lead to a better understanding of trastuzumab pharmacokinetics in the cerebrospinal fluid and serum.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17159499", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 102, "text": "Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17785760", "endSection": "sections.0" }, { "offsetInBeginSection": 1395, "offsetInEndSection": 1547, "text": "The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17785760", "endSection": "sections.0" }, { "offsetInBeginSection": 308, "offsetInEndSection": 393, "text": "response to anti-human epidermal growth factor receptor 2 (HER2) therapy trastuzumab.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20590449", "endSection": "sections.0" } ] }, { "body": "Which calcium channels does ethosuximide target?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21596106", "http://www.ncbi.nlm.nih.gov/pubmed/15078185", "http://www.ncbi.nlm.nih.gov/pubmed/15638774", "http://www.ncbi.nlm.nih.gov/pubmed/17291698", "http://www.ncbi.nlm.nih.gov/pubmed/24933286", "http://www.ncbi.nlm.nih.gov/pubmed/11641441", "http://www.ncbi.nlm.nih.gov/pubmed/10882031", "http://www.ncbi.nlm.nih.gov/pubmed/19005061", "http://www.ncbi.nlm.nih.gov/pubmed/26089446", "http://www.ncbi.nlm.nih.gov/pubmed/22924591", "http://www.ncbi.nlm.nih.gov/pubmed/21112351", "http://www.ncbi.nlm.nih.gov/pubmed/16171802", "http://www.ncbi.nlm.nih.gov/pubmed/21148095" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0033989", "o": "D015220" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0034034", "o": "D015220" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0034035", "o": "D015220" } ], "ideal_answer": [ "Ethosuximide blocks the T-type calcium channels." ], "exact_answer": [ "T-type calcium channels" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020747", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005013", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015220", "http://www.biosemantics.org/jochem#4249275" ], "type": "factoid", "id": "56cf236f3975bb303a000002", "snippets": [ { "offsetInBeginSection": 463, "offsetInEndSection": 685, "text": "In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933286", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1565, "text": "In rats, intraplantar (i.pl.) administration of db-cAMP or PGE(2) caused mechanical hyperalgesia, an effect suppressed by AKAPI, two distinct T-channel blockers, NNC 55-0396 and ethosuximide, or ZnCl(2) , known to inhibit Ca(v) 3.2 among T channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22924591", "endSection": "abstract" }, { "offsetInBeginSection": 1059, "offsetInEndSection": 1194, "text": "Theta rhythms remained disrupted during a subsequent week of withdrawal but were restored with the T-type channel blocker ethosuximide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21148095", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 604, "text": "Given evidence that chemotherapy-induced neuropathic pain is blocked by ethosuximide, known to block T-type calcium channels, we examined if more selective T-type calcium channel blockers and also inhibitors of cystathionine-\u03b3-lyase (CSE), a major H\u2082S-forming enzyme in the peripheral tissue, are capable of reversing the neuropathic pain evoked by paclitaxel, an anti-cancer drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596106", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 1073, "text": "The results demonstrate that both ethosuximide and the active metabolite of methsuximide, alpha-methyl-alpha-phenylsuccinimide (MPS), block human T-type channels in a state-dependent manner, with higher affinity for inactivated channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11641441", "endSection": "abstract" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1455, "text": "T-type channels display current at the end of long pulses (persistent current), and this current was especially sensitive to block (ethosuximide IC(50) = 0.6 mM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11641441", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 882, "text": "We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The antihyperalgesic effects of the T-type calcium channel blockers ethosuximide, trimethadione, and mibefradil.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16171802", "endSection": "title" }, { "offsetInBeginSection": 505, "offsetInEndSection": 595, "text": "Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10882031", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1256, "text": "The Ca(v)3.2 channel is sensitive to ethosuximide, amlodipine and amiloride.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15078185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The purpose of the present study was to explore the analgesic effects of the low voltage-activated T-type Ca2+ channel blockers ethosuximide, trimethadione, and mibefradil in persistent and acute nociceptive tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16171802", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 611, "text": "We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112351", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 436, "text": "We focused on two T-type calcium blockers, trimethadione and ethosuximide, which are anti-epileptics approved by the Food and Drug Administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17291698", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 509, "text": "Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10882031", "endSection": "abstract" } ] }, { "body": "What is the sedimentation coefficient of the mammalian mitoribosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11402041", "http://www.ncbi.nlm.nih.gov/pubmed/15966747", "http://www.ncbi.nlm.nih.gov/pubmed/11943462", "http://www.ncbi.nlm.nih.gov/pubmed/14757048", "http://www.ncbi.nlm.nih.gov/pubmed/6284743", "http://www.ncbi.nlm.nih.gov/pubmed/19567276" ], "ideal_answer": [ "The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits." ], "exact_answer": [ "55 S" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005762", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005761", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012270", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005840", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003735" ], "type": "factoid", "id": "55201a316b348bb82c000019", "snippets": [ { "offsetInBeginSection": 75, "offsetInEndSection": 119, "text": " The mammalian mitochondrial ribosomes (55S)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11943462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11402041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The 55 S mammalian mitochondrial ribosome (referred to hereafter as \"mitoribosome\") is protein-rich, containing nearly twice as much protein as the Escherichia coli ribosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6284743", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 860, "text": "59 of 78 proteins of the 55S mitoribosome, several TIM and TOM proteins and cell death proteins were present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19567276", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 344, "text": "The sedimentation coefficient of the intact monosome was about 55 S. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15966747", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1024, "text": "Though the nematode mitoribosome has a larger size than the bacterial ribosome, it does not differ significantly in size from mammalian mitoribosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15966747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The mammalian mitochondrial (mt) ribosome (mitoribosome) is a bacterial-type ribosome but has a highly protein-rich composition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14757048", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of aliskiren. ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19183745", "http://www.ncbi.nlm.nih.gov/pubmed/19895758", "http://www.ncbi.nlm.nih.gov/pubmed/23355128", "http://www.ncbi.nlm.nih.gov/pubmed/20812878", "http://www.ncbi.nlm.nih.gov/pubmed/23087256", "http://www.ncbi.nlm.nih.gov/pubmed/20467589", "http://www.ncbi.nlm.nih.gov/pubmed/25534713", "http://www.ncbi.nlm.nih.gov/pubmed/21687346", "http://www.ncbi.nlm.nih.gov/pubmed/23438929", "http://www.ncbi.nlm.nih.gov/pubmed/23723254", "http://www.ncbi.nlm.nih.gov/pubmed/18374681", "http://www.ncbi.nlm.nih.gov/pubmed/20380486", "http://www.ncbi.nlm.nih.gov/pubmed/21285669", "http://www.ncbi.nlm.nih.gov/pubmed/23418282", "http://www.ncbi.nlm.nih.gov/pubmed/22522051", "http://www.ncbi.nlm.nih.gov/pubmed/19337534", "http://www.ncbi.nlm.nih.gov/pubmed/24003484", "http://www.ncbi.nlm.nih.gov/pubmed/20019471", "http://www.ncbi.nlm.nih.gov/pubmed/20019472", "http://www.ncbi.nlm.nih.gov/pubmed/19066408", "http://www.ncbi.nlm.nih.gov/pubmed/23764715", "http://www.ncbi.nlm.nih.gov/pubmed/20203685", "http://www.ncbi.nlm.nih.gov/pubmed/20675959", "http://www.ncbi.nlm.nih.gov/pubmed/18443751", "http://www.ncbi.nlm.nih.gov/pubmed/21779913", "http://www.ncbi.nlm.nih.gov/pubmed/23174623", "http://www.ncbi.nlm.nih.gov/pubmed/22387646", "http://www.ncbi.nlm.nih.gov/pubmed/19279548", "http://www.ncbi.nlm.nih.gov/pubmed/21628356", "http://www.ncbi.nlm.nih.gov/pubmed/20957132" ], "ideal_answer": [ "Aliskiren is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks renin and consequential angiotensin I generation. Renin inhibition interrupts the renin-angiotensin-aldosterone system (RAAS)." ], "concepts": [ "http://www.biosemantics.org/jochem#4240636" ], "type": "summary", "id": "54e221f6ae9738404b000010", "snippets": [ { "offsetInBeginSection": 364, "offsetInEndSection": 494, "text": "Preliminary assignment a direct renin inhibitor aliskiren enhances the diuretic, natriuretic and kaliyuretic effects of the drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24003484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Aliskiren: An orally active renin inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21687346", "endSection": "title" }, { "offsetInBeginSection": 583, "offsetInEndSection": 748, "text": "Optimization of this compound by Novartis led to the development of aliskiren - the only direct renin inhibitor which is clinically used as an antihypertensive drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21687346", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 979, "text": "Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21687346", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 462, "text": "Aliskiren is a direct renin inhibitor that interrupts the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21285669", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 780, "text": "THE READER WILL GAIN: Aliskiren, the first approved renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks angiotensin I generation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20812878", "endSection": "abstract" }, { "offsetInBeginSection": 1414, "offsetInEndSection": 1561, "text": "TAKE HOME MESSAGE: The DRI aliskiren is an effective antihypertensive agent that preliminary data suggests has a beneficial effect in CVD and CKD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20380486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Aliskiren is a novel molecule which blocks the renin-angiotensin-aldosterone system in its rate limiting step by renin inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "After discovery of the first direct renin inhibitor, aliskiren, which blocks the renin-angiotensin-aldosterone system in the first rate limiting step, in addition to angiotensin-converting enzymes (ACE) and angiotensin-receptor blockers (ARB), renin has become an important target nowadays. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Aliskiren, the first orally effective direct renin inhibitor, is an effective antihypertensive agent with distinctive properties including placebo-like tolerability, pharmacologic effects that persist after drug discontinuation, and a unique mechanism of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19895758", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 873, "text": "Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19183745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19066408", "endSection": "title" }, { "offsetInBeginSection": 112, "offsetInEndSection": 267, "text": "One drug that emerged from this effort is aliskiren, a direct human renin inhibitor that blocks the conversion of angiotensinogen to angiotensin I (Ang I).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19066408", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1111, "text": "With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21285669", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 561, "text": "In the ALTITUDE trial the use of the direct renin inhibitor, aliskiren, was associated with hypotensive episodes and an excess of ischaemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23418282", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 222, "text": "Renin is the rate limiting enzyme of the RAAS and aliskiren is a highly potent and selective inhibitor of the human renin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534713", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 243, "text": "Aliskiren, the first direct renin inhibitor to be approved for the treatment of hypertension, blocks the RAAS at its point of activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20203685", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1110, "text": "With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21285669", "endSection": "abstract" } ] }, { "body": "Which proteins act as histone-like molecules in prokaryotes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14596799", "http://www.ncbi.nlm.nih.gov/pubmed/6253884", "http://www.ncbi.nlm.nih.gov/pubmed/23818873", "http://www.ncbi.nlm.nih.gov/pubmed/12220682", "http://www.ncbi.nlm.nih.gov/pubmed/3282561", "http://www.ncbi.nlm.nih.gov/pubmed/9016640", "http://www.ncbi.nlm.nih.gov/pubmed/11278072", "http://www.ncbi.nlm.nih.gov/pubmed/1925023", "http://www.ncbi.nlm.nih.gov/pubmed/15556475", "http://www.ncbi.nlm.nih.gov/pubmed/10645441", "http://www.ncbi.nlm.nih.gov/pubmed/16911001", "http://www.ncbi.nlm.nih.gov/pubmed/1549572", "http://www.ncbi.nlm.nih.gov/pubmed/656568", "http://www.ncbi.nlm.nih.gov/pubmed/14711120", "http://www.ncbi.nlm.nih.gov/pubmed/8339930", "http://www.ncbi.nlm.nih.gov/pubmed/667214", "http://www.ncbi.nlm.nih.gov/pubmed/6294066", "http://www.ncbi.nlm.nih.gov/pubmed/15102446", "http://www.ncbi.nlm.nih.gov/pubmed/18515342", "http://www.ncbi.nlm.nih.gov/pubmed/7748943", "http://www.ncbi.nlm.nih.gov/pubmed/11075932", "http://www.ncbi.nlm.nih.gov/pubmed/12056890", "http://www.ncbi.nlm.nih.gov/pubmed/21463569" ], "ideal_answer": [ "Prokaryotic histone-like proteins (Hlps) or nucleoid-associated proteins (NAPs) are abundant proteins found in bacterial and plastid nucleoids. HU protein is a small, basic, heat-stable DNA-binding protein that is well-conserved in prokaryotes and is associated with the bacterial nucleoid. HU is well conserved in all prokaryotes but surprisingly, it is also homologous to another E. coli DNA-binding protein, IHF. In prokaryotes, IHF and HU are key architectural proteins present at high concentrations. Histone-like Nucleoid Structuring (H-NS) protein can facilitate correct recognition of a promoter by RNA polymerase in AT-rich gene regulatory regions", "THe histone-like proteins HU, IHF, H-NS (Nucleoid Structuring) act as histones in prokaryotes" ], "exact_answer": [ [ "HU" ], [ "IHF" ], [ "H-NS" ] ], "concepts": [ "http://www.uniprot.org/uniprot/HNS_ECO57", "http://www.uniprot.org/uniprot/H33L2_CAEEL", "http://www.uniprot.org/uniprot/HLP_RICCN", "http://www.uniprot.org/uniprot/H2AZL_XENTR", "http://www.uniprot.org/uniprot/H13_CAEEL", "http://www.uniprot.org/uniprot/HNS_SALPA", "http://www.uniprot.org/uniprot/HLP_RICMO", "http://www.uniprot.org/uniprot/H33L1_CAEEL", "http://www.uniprot.org/uniprot/HNS_SALTI", "http://www.uniprot.org/uniprot/HLP_RICTY", "http://www.uniprot.org/uniprot/HLP_RICRI", "http://www.uniprot.org/uniprot/HLP_RICPR", "http://www.uniprot.org/uniprot/H3L_ENCCU", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.uniprot.org/uniprot/DBH_GUITH", "http://www.uniprot.org/uniprot/HNS_SALTY", "http://www.uniprot.org/uniprot/HNS_ECOLI", "http://www.uniprot.org/uniprot/H3L3_LILLO", "http://www.uniprot.org/uniprot/DBH_MYCS2", "http://www.uniprot.org/uniprot/H3L2_LILLO", "http://www.uniprot.org/uniprot/HNS_PROVU", "http://www.uniprot.org/uniprot/B4_XENLA", "http://www.uniprot.org/uniprot/YMOA_YERPE", "http://www.biosemantics.org/jochem#4278518", "http://www.uniprot.org/uniprot/HDAH_ALCSD", "http://www.uniprot.org/uniprot/H16_CAEEL", "http://www.uniprot.org/uniprot/H3L2_ARATH", "http://www.uniprot.org/uniprot/H14_CAEEL", "http://www.uniprot.org/uniprot/HQ1_COXBU", "http://www.uniprot.org/uniprot/SKP_ECOLI", "http://www.uniprot.org/uniprot/DBH_MYCLE", "http://www.uniprot.org/uniprot/H15_CAEEL", "http://www.uniprot.org/uniprot/H3L1_LILLO", "http://www.uniprot.org/uniprot/DBH_MYCBO", "http://www.uniprot.org/uniprot/YMOA_YEREN", "http://www.uniprot.org/uniprot/HNS_ECOL6", "http://www.uniprot.org/uniprot/HLP_RICBR", "http://www.uniprot.org/uniprot/HNS_SERMA", "http://www.uniprot.org/uniprot/H3L5_ARATH", "http://www.uniprot.org/uniprot/H3L4_ARATH", "http://www.uniprot.org/uniprot/H3L1_ARATH", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011387", "http://www.uniprot.org/uniprot/H3L3_ARATH", "http://www.uniprot.org/uniprot/H3CL_BOVIN", "http://www.uniprot.org/uniprot/18C_DROME", "http://www.uniprot.org/uniprot/DBH_MYCTU", "http://www.uniprot.org/uniprot/H12_CAEEL", "http://www.uniprot.org/uniprot/HC2D_CHLTR", "http://www.uniprot.org/uniprot/HLP_RICFE", "http://www.uniprot.org/uniprot/H2AZL_XENLA", "http://www.uniprot.org/uniprot/H1X_CAEEL" ], "type": "list", "id": "52ef7754c8da898910000014", "snippets": [ { "offsetInBeginSection": 233, "offsetInEndSection": 396, "text": "We show that Histone-like Nucleoid Structuring (H-NS) protein can facilitate correct recognition of a promoter by RNA polymerase in AT-rich gene regulatory regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818873", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 277, "text": "One feature is a histone-like protein that is associated with the DNA, condensing it into subunits similar to those in eukaryotic chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/656568", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 556, "text": "Recently the histone-like proteins were found in some primitive eucaryotes and procaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/667214", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 499, "text": "The relationship between HMGs (1 + 2) and the \"primitive\" histone-like DNA-packaging proteins from prokaryotes and mitochondria is discussed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6253884", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 593, "text": "The amino acid composition of the protein resembled those of the other prokaryotic histone-like proteins and also to eukaryotic histones H2A and H2B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6294066", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 717, "text": "In prokaryotes and in the pool of vegetative phage DNA the most abundant histone-like protein HU is not associated with the bulk DNA, but localised in the border region with ribosomes where transcription and translation occur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3282561", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 255, "text": "Like the histones, HU is able to condense DNA in vitro and to introduce negative super-coiling in covalently closed circular, relaxed DNA molecules in the presence of topoisomerase I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1925023", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 380, "text": "HU is well conserved in all prokaryotes but surprisingly, it is also homologous to another E. coli DNA-binding protein, IHF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1925023", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 377, "text": "Here we describe the identification of two developmental stage-specific genes, one of which is predicted to encode a 26-kDa lysine- and alanine-rich protein that appears to be homologous to several eukaryotic histone H1 proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1549572", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 662, "text": "No sequence homology was observed between this protein and other bacterial \"histone-like\" chromosomal proteins, but homology does exist with two other recently described prokaryotic proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1549572", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 358, "text": "In this study we show that these proteins can substitute for the prokaryotic DNA-bending protein HU in promoting the assembly of the Hin invertasome, an intermediate structure in Hin-mediated site-specific DNA inversion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8339930", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 259, "text": "We have characterized the role of HU in assembling the invertasome, an intermediate nucleoprotein complex involved in Hin-mediated site-specific recombination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7748943", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1052, "text": "Using ligase-mediated circularization of short DNA fragments we also show that HU, the high mobility group (HMG) 1 and 2 proteins from mammals, and a protein from yeast can bend DNA extremely efficiently", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7748943", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 512, "text": "The repression of transcription of two overlapping promoters of the gal operon in Escherichia coli requires Gal repressor (GalR) and the histone-like protein HU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9016640", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 910, "text": "We report GalR mediated DNA looping in which HU plays an obligatory role by helping GalR tetramerization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9016640", "endSection": "abstract" }, { "offsetInBeginSection": 1758, "offsetInEndSection": 1878, "text": "The protein has unique dual domains with homology to both bacterial histone-like proteins (HU) and eukaryotic histone H1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10645441", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1093, "text": " Four out of seven multi-copy suppressors were identified to encode HU, (3 for HUalpha and 1 for HUB) a histone-like DNA binding protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11075932", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 68, "text": "oles of Escherichia coli histone-like protein HU in DNA replication", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11278072", "endSection": "title" }, { "offsetInBeginSection": 4, "offsetInEndSection": 149, "text": "HU protein is a small, basic, heat-stable DNA-binding protein that is well-conserved in prokaryotes and is associated with the bacterial nucleoid", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11278072", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 95, "text": "role of surface-exposed lysines in wrapping DNA about the bacterial histone-like protein HU", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12056890", "endSection": "title" }, { "offsetInBeginSection": 8, "offsetInEndSection": 105, "text": "basic proteins, including the ubiquitous HU proteins, serve histone-like functions in prokaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12056890", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 136, "text": "modification of E. coli histone-like protein H-NS and bovine histones by short-chain poly-(R)-3-hydroxybutyrate (cPHB)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12220682", "endSection": "title" }, { "offsetInBeginSection": 362, "offsetInEndSection": 484, "text": "Here we examine Escherichia coli protein H-NS and calf thymus histones, H1, H2A, H2B, H3, and H4, for the presence of cPHB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12220682", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 583, "text": "The process requires negatively supercoiled DNA and the presence of the histone-like protein HU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14596799", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 659, "text": "Characterization of the major DNA-binding proteins of nucleoids revealed essential differences in the two lineages of photosynthetic eukaryotes, namely nucleoids of green plants contain sulfite reductase as a major DNA-binding protein that represses the genomic activity, whereas the prokaryotic DNA-binding protein HU is abundant in plastid nucleoids of the rhodophyte lineage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14711120", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 258, "text": "In prokaryotes, IHF and HU are key architectural proteins present at high concentrations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15102446", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 368, "text": "The deficit of TFs in some genomes might be compensated by the presence of proteins organizing and compacting DNA, such as histone-like proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15556475", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 103, "text": "okaryotic histone-like proteins (Hlps) are abundant proteins found in bacterial and plastid nucleoids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911001", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 143, "text": "n mesophilic prokaryotes, the DNA-binding protein HU participates in nucleoid organization as well as in regulation of DNA-dependent processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18515342", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 383, "text": "We show here that HU from the hyperthermophilic eubacterium Thermotoga maritima HU bends DNA and constrains negative DNA supercoils in the presence of topoisomerase I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18515342", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1319, "text": " We suggest that T. maritima HU serves an architectural function when associating with a single 35 bp site, but generates a very stable and compact aggregate at higher protein concentrations that organizes and protects the genomic DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18515342", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 104, "text": "ittle is known about the structure and function of most nucleoid-associated proteins (NAPs) in bacteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21463569", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 548, "text": "n this study, we investigate the distribution of HU in Caulobacter crescentus using a combination of super-resolution fluorescence imaging and spatial point statistics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21463569", "endSection": "abstract" } ] }, { "body": "Which receptor is targeted by telcagepant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21350792", "http://www.ncbi.nlm.nih.gov/pubmed/23196486", "http://www.ncbi.nlm.nih.gov/pubmed/20416945", "http://www.ncbi.nlm.nih.gov/pubmed/23480465", "http://www.ncbi.nlm.nih.gov/pubmed/23975906", "http://www.ncbi.nlm.nih.gov/pubmed/19157980", "http://www.ncbi.nlm.nih.gov/pubmed/21070230", "http://www.ncbi.nlm.nih.gov/pubmed/21480950", "http://www.ncbi.nlm.nih.gov/pubmed/19036425", "http://www.ncbi.nlm.nih.gov/pubmed/21110235", "http://www.ncbi.nlm.nih.gov/pubmed/18808506", "http://www.ncbi.nlm.nih.gov/pubmed/20099900", "http://www.ncbi.nlm.nih.gov/pubmed/19795182", "http://www.ncbi.nlm.nih.gov/pubmed/19770473", "http://www.ncbi.nlm.nih.gov/pubmed/20954694", "http://www.ncbi.nlm.nih.gov/pubmed/21054362", "http://www.ncbi.nlm.nih.gov/pubmed/17914062", "http://www.ncbi.nlm.nih.gov/pubmed/22816019", "http://www.ncbi.nlm.nih.gov/pubmed/19551474", "http://www.ncbi.nlm.nih.gov/pubmed/21383046", "http://www.ncbi.nlm.nih.gov/pubmed/22512641", "http://www.ncbi.nlm.nih.gov/pubmed/20826335", "http://www.ncbi.nlm.nih.gov/pubmed/19939188", "http://www.ncbi.nlm.nih.gov/pubmed/20120204", "http://www.ncbi.nlm.nih.gov/pubmed/19796656", "http://www.ncbi.nlm.nih.gov/pubmed/18590336", "http://www.ncbi.nlm.nih.gov/pubmed/21457238", "http://www.ncbi.nlm.nih.gov/pubmed/17929795", "http://www.ncbi.nlm.nih.gov/pubmed/19737844", "http://www.ncbi.nlm.nih.gov/pubmed/19914210", "http://www.ncbi.nlm.nih.gov/pubmed/19469188", "http://www.ncbi.nlm.nih.gov/pubmed/19779958", "http://www.ncbi.nlm.nih.gov/pubmed/20573757", "http://www.ncbi.nlm.nih.gov/pubmed/19219746", "http://www.ncbi.nlm.nih.gov/pubmed/19084002", "http://www.ncbi.nlm.nih.gov/pubmed/18039958", "http://www.ncbi.nlm.nih.gov/pubmed/18799366", "http://www.ncbi.nlm.nih.gov/pubmed/20188075", "http://www.ncbi.nlm.nih.gov/pubmed/20078608", "http://www.ncbi.nlm.nih.gov/pubmed/21221171", "http://www.ncbi.nlm.nih.gov/pubmed/25107879", "http://www.ncbi.nlm.nih.gov/pubmed/21070229", "http://www.ncbi.nlm.nih.gov/pubmed/22090312", "http://www.ncbi.nlm.nih.gov/pubmed/20855369", "http://www.ncbi.nlm.nih.gov/pubmed/20173082", "http://www.ncbi.nlm.nih.gov/pubmed/19579177", "http://www.ncbi.nlm.nih.gov/pubmed/22278333", "http://www.ncbi.nlm.nih.gov/pubmed/20974601", "http://www.ncbi.nlm.nih.gov/pubmed/21631478", "http://www.ncbi.nlm.nih.gov/pubmed/18217201", "http://www.ncbi.nlm.nih.gov/pubmed/23798725", "http://www.ncbi.nlm.nih.gov/pubmed/20164785", "http://www.ncbi.nlm.nih.gov/pubmed/20433208", "http://www.ncbi.nlm.nih.gov/pubmed/19346171", "http://www.ncbi.nlm.nih.gov/pubmed/18991732", "http://www.ncbi.nlm.nih.gov/pubmed/20937606", "http://www.ncbi.nlm.nih.gov/pubmed/22221076" ], "ideal_answer": [ "Telcagepant (MK-0974) is a novel calcitonin gene-related peptide (CGRP) receptor antagonist currently undergoing clinical trials for migraine." ], "exact_answer": [ "calcitonin gene-related peptide" ], "type": "factoid", "id": "55032efde9bde69634000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23975906", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan: results from a randomized study in patients with migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23798725", "endSection": "title" }, { "offsetInBeginSection": 684, "offsetInEndSection": 963, "text": "Olcegepant is the first selective CGRP receptor antagonist of proven efficacy in migraine. Olcegepant could only be administered intravenously and never taken beyond Phase II. Telcagepant is orally available and several completed Phase III trials have revealed positive results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Telcagepant (MK-0974) is a novel calcitonin gene-related peptide (CGRP) receptor antagonist currently undergoing clinical trials for migraine (http://www.merck.com/research/pipeline/home.html).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22816019", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 765, "text": "Four chemically unrelated CGRP receptor (CGRP-R) antagonists (olcegepant, telcagepant, MK-3207 and BI 44370 TA) have displayed efficacy in the treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22512641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being evaluated for acute migraine treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22278333", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 328, "text": "BACKGROUND: Calcitonin gene-related peptide receptor antagonists, such as telcagepant, may be useful for acute migraine treatment in patients with cardiovascular disease, a population for whom triptans are contraindicated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22221076", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 683, "text": "The calcitonin gene-related peptide (CGRP) receptor antagonists (gepants)-olcegepant (BIBN 4096 BS), telcagepant (MK-0974), MK3207, and BI 44370 TA-are effective in treating acute migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090312", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 438, "text": "Telcagepant, a calcitonin gene-related peptide receptor antagonist, is being developed for the acute treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21631478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21480950", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "AIMS: To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21480950", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 307, "text": "BACKGROUND: Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21457238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "BACKGROUND: The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21383046", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 995, "text": "CONCLUSION: The apparently high doses of CGRP receptor antagonists, olcegepant and telcagepant needed for anti-migraine effect are not so high after all. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21383046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21350792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "INTRODUCTION: Telcagepant (MK-0974) is a novel, orally active and selective CGRP receptor antagonist being investigated for acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21221171", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1469, "text": "Calcitonin gene-related peptide (CGRP) receptor antagonists are another promising nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) and telcagepant (MK-0974) have been shown to be safe and effective in phase I, II, and (for telcagepant) phase III clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21110235", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 263, "text": "Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "In 3 randomized clinical trials (n = 1585) the calcitonin gene-related peptide antagonist telcagepant 300 mg orally had an incidence of adverse events similar to placebo when used in the acute treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070229", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 246, "text": "BACKGROUND: Telcagepant is an oral calcitonin gene-related peptide receptor antagonist with acute antimigraine efficacy comparable to oral triptans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21054362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "METHODS: This study evaluated the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant (tablet formulation) for treatment of a migraine attack and across four attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20974601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20954694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Asymmetric synthesis of telcagepant, a CGRP receptor antagonist for the treatment of migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20954694", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Sustained pain freedom and no adverse events as an endpoint in clinical trials of acute migraine treatments: application to patient-level data from a trial of the CGRP receptor antagonist, telcagepant, and zolmitriptan.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937606", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 623, "text": "METHODS: The aim of this study was to evaluate new composite efficacy-plus-tolerability endpoints based on a post-hoc analysis of patient-level data from a previous randomized, placebo-controlled trial of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, and zolmitriptan in the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20855369", "endSection": "title" }, { "offsetInBeginSection": 182, "offsetInEndSection": 375, "text": "MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20855369", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1328, "text": "CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20855369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573757", "endSection": "title" }, { "offsetInBeginSection": 287, "offsetInEndSection": 585, "text": "We therefore investigated the effects of the antimigraine CGRP receptor antagonist telcagepant (MK-0974) [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)piperidine-1-carboxamide] on human isolated coronary arteries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573757", "endSection": "abstract" }, { "offsetInBeginSection": 1861, "offsetInEndSection": 2060, "text": "These findings in vitro support the cardiovascular safety of CGRP receptor antagonists and suggest that telcagepant is unlikely to induce coronary side effects under normal cardiovascular conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573757", "endSection": "abstract" }, { "offsetInBeginSection": 1115, "offsetInEndSection": 1482, "text": "Towards this end, the non-peptide CGRP receptor antagonists olcegepant and telcagepant have been shown to be effective in the acute treatment of migraine. While telcagepant is being pursued as a frontline abortive migraine drug in a phase III clinical trial, an oral formulation of a novel CGRP receptor antagonist, BI 44370, is currently in phase II clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20433208", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 340, "text": "Telcagepant represents a new class of antimigraine drug-the calcitonin gene-related peptide receptor blockers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20416945", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 634, "text": "The CGRP receptor antagonists telcagepant and olcegepant (BIBN4096BS) have demonstrated clinical efficacy in the treatment of migraine and there is now a need to better understand how these molecules interact with the receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20188075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173082", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Telcagepant is a novel, orally active, and selective calcitonin gene-related peptide receptor antagonist being developed for acute treatment of migraine with and without aura. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Studies were conducted in human isolated coronary arteries to explore the vascular effects of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant and to compare its coronary vasoconstrictive potential to that of zolmitriptan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20164785", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 848, "text": "Intravenous BIBN4096BS (olcegepant) and oral MK-0974 (telcagepant), two CGRP-receptor antagonists, were safe and effective in the treatment of migraine attacks in Phase I and II trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20120204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Telcagepant (MK-0974) is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist and is currently under clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19346171", "endSection": "abstract" } ] }, { "body": "What is the role of photodynamic therapy for meningioma treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "http://www.ncbi.nlm.nih.gov/pubmed/24486853", "http://www.ncbi.nlm.nih.gov/pubmed/23465372", "http://www.ncbi.nlm.nih.gov/pubmed/1984490", "http://www.ncbi.nlm.nih.gov/pubmed/8672259", "http://www.ncbi.nlm.nih.gov/pubmed/10327048", "http://www.ncbi.nlm.nih.gov/pubmed/2176016", "http://www.ncbi.nlm.nih.gov/pubmed/21073472", "http://www.ncbi.nlm.nih.gov/pubmed/16788926", "http://www.ncbi.nlm.nih.gov/pubmed/8384325", "http://www.ncbi.nlm.nih.gov/pubmed/2855780" ], "ideal_answer": [ "Photodynamic therapy was shown to have activity againt meningioma treatment. Gefitinib and ciprofloxacin enhance efficacy of photodynamic therapy." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3565", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812" ], "type": "summary", "id": "56c097deef6e394741000027", "snippets": [ { "offsetInBeginSection": 1221, "offsetInEndSection": 1382, "text": "CONCLUSIONS: Efficacy of 5-ALA PDT could be increased by adjunction of ciprofloxacin in conventional clinical dosing and by prolongation of ALA incubation time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24486853", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1187, "text": "CONCLUSION: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23465372", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1630, "text": "CONCLUSION: ALA-PDT was more effective in killing U-105MG glioma cells than CH-157MN meningioma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10327048", "endSection": "abstract" }, { "offsetInBeginSection": 1726, "offsetInEndSection": 1889, "text": "These data indicate unique features of AlPc which suggests its application as a potent, non-toxic photosensitizer in the photodynamic therapy of human meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8672259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8384325", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 735, "text": "It was found that PDT using haematoporphyrin derivative as a photosensitizing drug showed dose-dependent activity against a variety of histological subtypes of meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1984490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073472", "endSection": "title" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1425, "text": "We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073472", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 626, "text": "Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas but its activity against meningiomas has not been specifically studied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Enhancing the effect of 5-aminolevulinic acid based photodynamic therapy in human meningioma cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24486853", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "An in vitro study of the effect of photodynamic therapy on human meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "endSection": "title" }, { "offsetInBeginSection": 300, "offsetInEndSection": 465, "text": "Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas but its activity against meningiomas has not been specifically studied. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "endSection": "abstract" } ] }, { "body": "Do carmustine wafers improve survival of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18366283", "http://www.ncbi.nlm.nih.gov/pubmed/23118709", "http://www.ncbi.nlm.nih.gov/pubmed/18240917", "http://www.ncbi.nlm.nih.gov/pubmed/15937647", "http://www.ncbi.nlm.nih.gov/pubmed/21983866", "http://www.ncbi.nlm.nih.gov/pubmed/16482400", "http://www.ncbi.nlm.nih.gov/pubmed/25054300", "http://www.ncbi.nlm.nih.gov/pubmed/17938702", "http://www.ncbi.nlm.nih.gov/pubmed/21390826", "http://www.ncbi.nlm.nih.gov/pubmed/21344976", "http://www.ncbi.nlm.nih.gov/pubmed/23662801", "http://www.ncbi.nlm.nih.gov/pubmed/18035958", "http://www.ncbi.nlm.nih.gov/pubmed/12074689", "http://www.ncbi.nlm.nih.gov/pubmed/22715955", "http://www.ncbi.nlm.nih.gov/pubmed/25085219", "http://www.ncbi.nlm.nih.gov/pubmed/22718138", "http://www.ncbi.nlm.nih.gov/pubmed/21479583", "http://www.ncbi.nlm.nih.gov/pubmed/10414561", "http://www.ncbi.nlm.nih.gov/pubmed/17350791", "http://www.ncbi.nlm.nih.gov/pubmed/18636295", "http://www.ncbi.nlm.nih.gov/pubmed/21300471", "http://www.ncbi.nlm.nih.gov/pubmed/19123896", "http://www.ncbi.nlm.nih.gov/pubmed/15069758", "http://www.ncbi.nlm.nih.gov/pubmed/20155992", "http://www.ncbi.nlm.nih.gov/pubmed/23535992", "http://www.ncbi.nlm.nih.gov/pubmed/17334672", "http://www.ncbi.nlm.nih.gov/pubmed/19046047", "http://www.ncbi.nlm.nih.gov/pubmed/23350777", "http://www.ncbi.nlm.nih.gov/pubmed/21330749", "http://www.ncbi.nlm.nih.gov/pubmed/12672279", "http://www.ncbi.nlm.nih.gov/pubmed/25269031", "http://www.ncbi.nlm.nih.gov/pubmed/21756557", "http://www.ncbi.nlm.nih.gov/pubmed/20706757", "http://www.ncbi.nlm.nih.gov/pubmed/20511192", "http://www.ncbi.nlm.nih.gov/pubmed/24246204", "http://www.ncbi.nlm.nih.gov/pubmed/19514083", "http://www.ncbi.nlm.nih.gov/pubmed/15015668" ], "ideal_answer": [ "Yes, it has been documented that implantation of carmustine wafers improves survival of newly diagnosed and recurrent glioblastoma patients." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4275776" ], "type": "yesno", "id": "54d630283706e89528000004", "snippets": [ { "offsetInBeginSection": 338, "offsetInEndSection": 472, "text": "At recurrence, treatment options include repeat surgery (with or without Gliadel wafer placement), reirradiation or systemic therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25054300", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1909, "text": "DISCUSSION: Carmustine wafers for primary HGG surgery in accordance with the NICE TA121 were associated with a median survival of 15.3 months; this is improved compared with previously reported randomised trials. Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22715955", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 886, "text": "Gliadel wafer is a new approach to the treatment of glioblastoma, which involves controlled release delivery of carmustine from biodegradable polymer wafers. It has shown promising results and provides a silver lining for glioblastoma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330749", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 745, "text": "For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300471", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1371, "text": "According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300471", "endSection": "abstract" }, { "offsetInBeginSection": 1821, "offsetInEndSection": 1945, "text": "CONCLUSION: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20706757", "endSection": "abstract" }, { "offsetInBeginSection": 2138, "offsetInEndSection": 2438, "text": "CONCLUSIONS: The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19123896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "OBJECT: Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19046047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "BACKGROUND: Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly used for local delivery of BCNU to high-grade gliomas after resection and is associated with increased survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18636295", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 719, "text": "Temozolomide administered according to this protocol produced a median survival benefit of 2 months in glioblastomas, and carmustine a similar benefit in high-grade gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350791", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 455, "text": "Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16482400", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1360, "text": "Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16482400", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1689, "text": "CONCLUSION: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16482400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "OBJECTIVE: Recently a randomized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15015668", "endSection": "abstract" }, { "offsetInBeginSection": 1810, "offsetInEndSection": 2051, "text": "CONCLUSION: In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy, resulting in an increased survival time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15015668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12672279", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1198, "text": "Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12672279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Controlled release delivery of carmustine from biodegradable polymer wafers was approved as an adjunct to surgical resection in the treatment of recurrent glioblastoma multiforme after it was shown in clinical trials to be well tolerated and effective. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12074689", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 513, "text": "Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20155992", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1767, "text": "BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20155992", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1717, "text": "CONCLUSIONS: Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19514083", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1518, "text": "Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23535992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21756557", "endSection": "title" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1826, "text": "DISCUSSION: Older patients with GBM may benefit from carmustine wafers. The survival for older patients who received carmustine wafers is significantly longer than matched patients who did not receive carmustine wafers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21756557", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 958, "text": "For glioblastoma patients who received \u226590% resection in the BCNU wafer study, median survival increased for BCNU wafer versus placebo (14.5 versus 12.4\u00a0months, respectively; P\u2009=\u20090.02), but no survival increase was found for <90% resection (11.7 versus 10.6\u00a0months, respectively; P\u2009=\u20090.98).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479583", "endSection": "abstract" }, { "offsetInBeginSection": 1923, "offsetInEndSection": 2144, "text": "A wafer impregnated with carmustine, for use as an implant after surgical removal of recurrent GBM showed a prolongation in the median survival time of only 2 mo, from 20 to 28 wk in a study with a total of 222 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21390826", "endSection": "abstract" }, { "offsetInBeginSection": 1620, "offsetInEndSection": 1696, "text": "No clear survival benefit associated with wafer implantation was identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10414561", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 866, "text": "In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269031", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1298, "text": "TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246204", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 519, "text": "The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118709", "endSection": "abstract" }, { "offsetInBeginSection": 1365, "offsetInEndSection": 1644, "text": "For patients undergoing repeat resection for malignant glioma, a randomized, blinded, placebo-controlled trial demonstrated a median survival for 110 patients who received carmustine polymers of 31 weeks compared with 23 weeks for 122 patients who only received placebo polymers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118709", "endSection": "abstract" }, { "offsetInBeginSection": 1977, "offsetInEndSection": 2261, "text": "Median survival was improved from 11.6 to 13.9 months (P = 0.03), with a 29% reduction in the risk of death. When patients with glioblastoma multiforme alone were analyzed, the median survival improved from 11.4 to 13.5 months, but this improvement was not statistically significant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "OBJECT: Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23350777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17334672", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 518, "text": "The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118709", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1266, "text": "However, patients with carmustine wafers demonstrated prolonged survival as compared to patients without wafers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21756557", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1414, "text": "The median survival for patients with carmustine wafers was 8.7 months, while median survival for patients without wafers was 5.5 months (P=0.007).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21756557", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1606, "text": "Likewise, in subgroup analysis, patients older than 70 years (P=0.0003) and 75 years (P=0.04) who had carmustine wafers had significantly longer survival than matched patients without wafers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21756557", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 954, "text": "Implantation of carmustine wafers did not significantly improve progression-free survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269031", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 863, "text": "In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12672279", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 397, "text": "A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12672279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17334672", "endSection": "abstract" }, { "offsetInBeginSection": 1722, "offsetInEndSection": 1854, "text": "Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22715955", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 517, "text": "The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118709", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1296, "text": "TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246204", "endSection": "abstract" } ] }, { "body": "Is Dicer part of the RISC loading complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23511973", "http://www.ncbi.nlm.nih.gov/pubmed/23272173", "http://www.ncbi.nlm.nih.gov/pubmed/24303839", "http://www.ncbi.nlm.nih.gov/pubmed/23424633", "http://www.ncbi.nlm.nih.gov/pubmed/23550157", "http://www.ncbi.nlm.nih.gov/pubmed/23226452" ], "triples": [ { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/A0MQH0", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442", "o": "RNA-induced silencing complex" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_41304D5148300018", "o": "Endoribonuclease Dicer" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442", "o": "RISC complex" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/B3DLA6", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4233444C4136001C", "o": "Endoribonuclease Dicer" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q25BN1", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513235424E310017", "o": "Endoribonuclease Dicer" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q6TUI4", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136545549340018", "o": "Endoribonuclease Dicer" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q6TV19", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513654563139001C", "o": "Endoribonuclease Dicer" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/A0MQH0", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0016442", "o": "http://www.geneontology.org/go#GO:0016442" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0016442", "o": "RISC complex" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0016442", "o": "RNA-induced silencing complex" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/B3DLA6", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q25BN1", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q6TUI4", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q6TV19", "o": "http://purl.uniprot.org/go/0016442" } ], "ideal_answer": [ "Yes, Dicer is part of the RISC loading complex." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016442", "http://www.uniprot.org/uniprot/DCR1_SCHPO", "http://www.uniprot.org/uniprot/DICER_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070922", "http://www.uniprot.org/uniprot/DICER_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070578", "http://www.uniprot.org/uniprot/DICER_CRIGR", "http://www.uniprot.org/uniprot/DICER_MOUSE", "http://www.uniprot.org/uniprot/DICER_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043244", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034743" ], "type": "yesno", "id": "5516fc8832767d0305000002", "snippets": [ { "offsetInBeginSection": 121, "offsetInEndSection": 336, "text": "Dicer is a component of the protein machinery (the RNA Induced Silencing Complex [RISC]) which is involved in catalyzing the formation of mature microRNAs from their precursors in the process of microRNA biogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24303839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23550157", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23550157", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 761, "text": " Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23511973", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 307, "text": "RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23424633", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 510, "text": ". Dicer, an RNase III enzyme, plays a central role in the RNAi pathway by cleaving precursors of both of these classes of RNAs to form mature siRNAs and miRNAs, which are then loaded into the RNA-induced silencing complex (RISC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272173", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 616, "text": "Canonical siRNAs are 21 nucleotides (nt) in length and are loaded to the RNA Induced Silencing Complex when introduced into the cells, while longer siRNA molecules are first processed by endogenous Dicer and thus termed Dicer-substrate siRNA (DsiRNA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23226452", "endSection": "abstract" } ] }, { "body": "What is the Arnold-Chiari syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18546951", "http://www.ncbi.nlm.nih.gov/pubmed/19287845", "http://www.ncbi.nlm.nih.gov/pubmed/15785984", "http://www.ncbi.nlm.nih.gov/pubmed/17874345" ], "ideal_answer": [ "Arnold Chiari syndrome is a condition characterized by herniation of the cerebellar tonsils through the foramen magnum, manifesting usually with downbeat nystagmus, palsy of the caudal cerebral nerves, headache, and vertigo." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001139", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "summary", "id": "5318985eb166e2b80600001d", "snippets": [ { "offsetInBeginSection": 137, "offsetInEndSection": 256, "text": "Arnold Chiari syndrome is a condition characterized by herniation of the cerebellar tonsils through the foramen magnum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19287845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The Arnold-Chiari malformation is very rare hindbrain abnormalities characterized by herniation of the hindbrain through the foramen magnum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18546951", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 833, "text": "The origin of Arnold-Chiari syndrome is connected with narrowness in the posterior fossa, particularly with narrowing of the arachnoid spaces.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17874345", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 193, "text": "Arnold-Chiari Syndrome I is a malformation of the cervicomedullary junction, manifesting usually with downbeat nystagmus, palsy of the caudal cerebral nerves, headache, and vertigo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15785984", "endSection": "abstract" } ] }, { "body": "What is the biological role of SERCA2 SUMOylation in cardiac physiology and pathophysiology, such as in heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23710633", "http://www.ncbi.nlm.nih.gov/pubmed/22679139", "http://www.ncbi.nlm.nih.gov/pubmed/24225946", "http://www.ncbi.nlm.nih.gov/pubmed/21900893" ], "ideal_answer": [ "Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. SERCA2a is SUMOylated at lysines 480 and 585 and this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO-1 gene transfer improved cardiac function supporting the critical role of SUMO-1 in SERCA2a function and underlining the therapeutic potential of SUMO-1 for HF patients." ], "concepts": [ "http://www.uniprot.org/uniprot/AT2A2_RAT", "http://www.uniprot.org/uniprot/AT2A2_RABIT", "http://www.uniprot.org/uniprot/AT2A2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016925", "http://www.uniprot.org/uniprot/AT2A2_CHICK", "http://www.uniprot.org/uniprot/AT2A2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003301", "http://www.uniprot.org/uniprot/AT2A2_FELCA", "http://www.uniprot.org/uniprot/AT2A2_PIG", "http://www.uniprot.org/uniprot/AT2A2_CANFA" ], "type": "summary", "id": "5508453a4b2a315d41000008", "snippets": [ { "offsetInBeginSection": 874, "offsetInEndSection": 1132, "text": "SERCA2a activity can be regulated at multiple levels of a signaling cascade comprised of phospholamban, protein phosphatase 1, inhibitor-1, and PKC\u03b1. SERCA2 activity is also regulated by post-translational modifications including SUMOylation and acetylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23710633", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 880, "text": "The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900893", "endSection": "abstract" }, { "offsetInBeginSection": 1710, "offsetInEndSection": 1924, "text": "Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The amount of myocardial SUMO-1 is decreased in failing hearts, and its knockdown results in severe heart failure (HF) in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225946", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1618, "text": "SUMO-1 gene transfer therefore improved cardiac function and stabilized LV volumes in a large-animal model of HF. These results support the critical role of SUMO-1 in SERCA2a function and underline the therapeutic potential of SUMO-1 for HF patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225946", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 862, "text": "However, the initial simple view of a PLN/SERCA regulatory complex has been modified by our recent identification of SUMO, S100 and the histidine-rich Ca-binding protein as regulators of SERCA activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22679139", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 878, "text": "The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900893", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 780, "text": "Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900893", "endSection": "abstract" }, { "offsetInBeginSection": 1709, "offsetInEndSection": 1922, "text": "Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900893", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1131, "text": "SERCA2 activity is also regulated by post-translational modifications including SUMOylation and acetylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23710633", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 879, "text": "The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900893", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 781, "text": "Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900893", "endSection": "abstract" } ] }, { "body": "Which trinucleotide repeat disorders are affecting the nervous system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7998766", "http://www.ncbi.nlm.nih.gov/pubmed/17417937" ], "ideal_answer": [ "At least six neudegenerative disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), Huntington's disease (HD), spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA)." ], "exact_answer": [ [ "X-linked spinal and bulbar muscular atrophy (SBMA)" ], [ "Fragile X syndrome of mental retardation (FRAXA)" ], [ "Fragile X syndrome of mental retardation (FRAXE)" ], [ "Huntington's disease (HD)" ], [ "Spinocerebellar ataxia type 1 (SCA1)" ], [ "Dentatorubral-pallidoluysian atrophy (DRPLA)" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019680", "http://www.disease-ontology.org/api/metadata/DOID:863", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002493", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035753", "http://www.disease-ontology.org/api/metadata/DOID:331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018911", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009420", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009422" ], "type": "list", "id": "5319a724b166e2b806000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "The discovery that expansion of unstable repeats can cause a variety of neurological disorders has changed the landscape of disease-oriented research for several forms of mental retardation, Huntington disease, inherited ataxias, and muscular dystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17417937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "Expansion of trinucleotide repeats is now recognized as a major cause of neurological disease. At least seven disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7998766", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1054, "text": "Fragile X and myotonic dystrophy are multisystem disorders usually associated with large expansions of untranslated repeats, while the four neurodegenerative disorders, SBMA, Huntington's disease, SCA1, and DRPLA, are caused by smaller expansions of CAG repeats within the protein coding portion of the gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7998766", "endSection": "abstract" } ] }, { "body": "Is hypersensitivity to DNA crosslinking agents a hallmark of Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16904272", "http://www.ncbi.nlm.nih.gov/pubmed/8058745", "http://www.ncbi.nlm.nih.gov/pubmed/19275569", "http://www.ncbi.nlm.nih.gov/pubmed/15277238", "http://www.ncbi.nlm.nih.gov/pubmed/18047734", "http://www.ncbi.nlm.nih.gov/pubmed/22690333", "http://www.ncbi.nlm.nih.gov/pubmed/10526221", "http://www.ncbi.nlm.nih.gov/pubmed/19101576", "http://www.ncbi.nlm.nih.gov/pubmed/21240275", "http://www.ncbi.nlm.nih.gov/pubmed/22053284", "http://www.ncbi.nlm.nih.gov/pubmed/21478198", "http://www.ncbi.nlm.nih.gov/pubmed/22532920", "http://www.ncbi.nlm.nih.gov/pubmed/21568838", "http://www.ncbi.nlm.nih.gov/pubmed/20034732", "http://www.ncbi.nlm.nih.gov/pubmed/21109493", "http://www.ncbi.nlm.nih.gov/pubmed/25002988", "http://www.ncbi.nlm.nih.gov/pubmed/17396147", "http://www.ncbi.nlm.nih.gov/pubmed/19748364", "http://www.ncbi.nlm.nih.gov/pubmed/16493006", "http://www.ncbi.nlm.nih.gov/pubmed/23444773", "http://www.ncbi.nlm.nih.gov/pubmed/1809228", "http://www.ncbi.nlm.nih.gov/pubmed/19738377", "http://www.ncbi.nlm.nih.gov/pubmed/23318445", "http://www.ncbi.nlm.nih.gov/pubmed/20120016", "http://www.ncbi.nlm.nih.gov/pubmed/11751423", "http://www.ncbi.nlm.nih.gov/pubmed/21939290" ], "ideal_answer": [ "Yes, hypersensitivity to DNA crosslinking agents is one of the hallmarks of Fanconi anemia, the others being defective FANCD2 monoubiquitination, and genomic instability." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "yesno", "id": "54ecb66d445c3b5a5f000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "The Fanconi anemia (FA) core complex plays a central role in the DNA damage response network", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17396147", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 958, "text": "FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17396147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Fanconi anemia (FA) is a rare genetic disorder characterized by aplastic anemia, cancer/leukemia susceptibility and cellular hypersensitivity to DNA crosslinking agents, such as cisplatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18047734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Fanconi anemia (FA) is an inherited chromosomal recessive syndrome characterized by cellular hypersensitivity to DNA crosslinking agents and bone marrow failure, which cause aplastic anemia, and an increased incidence of malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19275569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8058745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Fanconi anemia (FA) is one of several genetic diseases with characteristic cellular hypersensitivity to DNA crosslinking agents which suggest that FA proteins may function as part of DNA repair processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10526221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remain unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Fanconi Anemia (FA) is a rare genetic disorder associated with a bone-marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25002988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Fanconi anemia (FA) is an inherited disorder characterized by defective DNA repair and cellular sensitivity to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21939290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure, increased cancer risk and hypersensitivity to DNA cross-linking agents, implying a role for this pathway in the maintenance of genomic stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20034732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Fanconi Anemia (FA) is a rare autosomic recessive and X-linked disease with chromosomal instability after exposure to crosslinking agents as the hallmark.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22053284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Fanconi Anemia (FA) is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22532920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The Bloom protein (BLM) and Topoisomerase IIIalpha are found in association with proteins of the Fanconi anemia (FA) pathway, a disorder manifesting increased cellular sensitivity to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19738377", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 958, "text": "Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17396147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16904272", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 381, "text": "FA is a chromosome instability syndrome characterized by childhood-onset aplastic anemia, cancer or leukemia susceptibility, and cellular hypersensitivity to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16493006", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 336, "text": "Functional defects in the Fanconi pathway can result in a marked hypersensitivity to interstrand crosslinking agents, such as mitomycin C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15277238", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 316, "text": "At the cellular level, hypersensitivity to DNA interstrand crosslinks is the defining feature in Fanconi anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21240275", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 644, "text": "DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Fanconi anemia (FA), an autosomal recessive disorder of children, is characterized by congenital or childhood aplastic anemia, multiple developmental anomalies, increased incidence of myeloid leukemia, increased spontaneous chromosome breakage, and cellular and chromosomal hypersensitivity to DNA bifunctional crosslinking and alkylating agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1809228", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 167, "text": "elegans provides an excellent model system for the study of the Fanconi Anemia (FA), one of the hallmarks of which is sensitivity to interstrand crosslinking agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22690333", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 957, "text": "Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17396147", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 316, "text": "One of the hallmark phenotypes of FA is cellular hypersensitivity to agents that induce DNA interstrand crosslinks (ICLs), such as mitomycin C (MMC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21478198", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 983, "text": "Furthermore, the cytological hallmark of FA, the DNA crosslink-induced radial chromosome formation, exemplifies an innate impairment in the repair of these particularly cytotoxic DNA lesions [A.D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19101576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remain unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8058745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Fanconi anemia (FA) is an inherited chromosomal recessive syndrome characterized by cellular hypersensitivity to DNA crosslinking agents and bone marrow failure, which cause aplastic anemia, and an increased incidence of malignancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19275569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20034732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Fanconi anemia (FA) is a human autosomal disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinking agents such as mitomycin C and diepoxybutane", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11751423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The Fanconi anemia pathway promotes DNA glycosylase-dependent excision of interstrand DNA crosslinks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20120016", "endSection": "title" }, { "offsetInBeginSection": 508, "offsetInEndSection": 643, "text": "DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444773", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 380, "text": "FA is a chromosome instability syndrome characterized by childhood-onset aplastic anemia, cancer or leukemia susceptibility, and cellular hypersensitivity to DNA crosslinking agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16493006", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 331, "text": "The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21568838", "endSection": "abstract" } ] }, { "body": "Which are the cellular targets of imatinib mesylate?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15887238", "http://www.ncbi.nlm.nih.gov/pubmed/15844661" ], "ideal_answer": [ "The cellular targets of imatinib mesylate are BCR-ABL, platelet-derived growth factor receptor (PDGFR) and c-kit kinases." ], "exact_answer": [ [ "BCR-ABL" ], [ "Platelet-derived growth factor receptor (PDGFR)" ], [ "c-Kit" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4275840", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016503", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017479", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058990" ], "type": "list", "id": "53188992b166e2b806000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Imatinib mesylate is a tyrosine kinase inhibitor of the ABL, platelet-derived growth factor receptor (PDGFR), and c-kit kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15887238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 477, "text": "Imatinib mesylate is a novel anti-tumor agent useful in the clinical management of chronic myelogenous leukemia and gastrointestinal stromal tumors with minimal toxicity relative to other forms of cancer therapy. Its clinical activity and minimal toxicity are related to specific inhibition of cellular targets including BCR-ABL, platelet-derived growth factor receptor and c-kit kinases, resulting in the collapse of downstream signaling cascades important for transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15844661", "endSection": "abstract" } ] }, { "body": "Which are the clinical characteristics of Tuberous Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14716484", "http://www.ncbi.nlm.nih.gov/pubmed/22791573", "http://www.ncbi.nlm.nih.gov/pubmed/19889303", "http://www.ncbi.nlm.nih.gov/pubmed/16210669", "http://www.ncbi.nlm.nih.gov/pubmed/24304436", "http://www.ncbi.nlm.nih.gov/pubmed/23219029", "http://www.ncbi.nlm.nih.gov/pubmed/23007140", "http://www.ncbi.nlm.nih.gov/pubmed/19133941", "http://www.ncbi.nlm.nih.gov/pubmed/11520735", "http://www.ncbi.nlm.nih.gov/pubmed/15221338", "http://www.ncbi.nlm.nih.gov/pubmed/24180681", "http://www.ncbi.nlm.nih.gov/pubmed/12618672", "http://www.ncbi.nlm.nih.gov/pubmed/19239998" ], "ideal_answer": [ "The clinical characteristics of Tuberous Sclerosis include epilepsy, subependymal giant cell astrocytomas, lymphangioleiomyomatosis, rhabdomyoma, renal angiomyolipomas, cortical tubers, neurofibromas, angiofibromas, mental retardation, and behavioral disorders." ], "exact_answer": [ [ "epilepsy" ], [ "subependymal giant cell astrocytomas" ], [ "lymphangioleiomyomatosis" ], [ "rhabdomyoma" ], [ "renal angiomyolipomas" ], [ "cortical tubers" ], [ "neurofibromas" ], [ "angiofibromas" ], [ "mental retardation" ], [ "behavioral disorders" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012640", "http://www.uniprot.org/uniprot/TSC2_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://www.uniprot.org/uniprot/TSC1_RAT", "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:557", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007674", "http://www.uniprot.org/uniprot/TSC1_SCHPO", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:850", "http://www.uniprot.org/uniprot/TSC2_SCHPO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008171", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008607", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:1059", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ], "type": "list", "id": "52ebb2c698d0239505000029", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 118, "text": "Prevalence and long-term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304436", "endSection": "abstract" }, { "offsetInBeginSection": 7, "offsetInEndSection": 134, "text": "Subependymal giant cell astrocytomas (SEGAs) are benign tumors, most commonly associated with tuberous sclerosis complex (TSC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24180681", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 142, "text": "Lymphangioleiomyomatosis (LAM) is a rare, progressive, frequently lethal cystic lung disease that almost exclusively affects women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23007140", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 162, "text": "Rhabdomyoma is the most common type of cardiac tumor in fetuses and is often associated with tuberous sclerosis complex (TSC) with neurologic sequelae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791573", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 552, "text": "In contrast to renal angiomyolipomas, which are often associated with tuberous sclerosis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19889303", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 183, "text": "clinical characteristics of subependymal nodule (SN) - subependymal giant cell astrocytoma (SGCA) complex in tuberous sclerosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19239998", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 830, "text": "NMI patients had a lower incidence of brain findings on imaging studies, neurological features, and renal findings than those with TSC2 mutations. In contrast, NMI patients had a lower incidence of seizures than TSC patients with TSC1 mutations, but had a higher incidence of both renal angiomyolipomas and pulmonary lymphangioleiomyomatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19133941", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 456, "text": "clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis-related forms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16210669", "endSection": "abstract" }, { "offsetInBeginSection": 1300, "offsetInEndSection": 1455, "text": "Women with tuberous sclerosis-related lymphangioleiomyomatosis were younger and had less impaired lung function compared with those with the sporadic form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16210669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylor's type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15221338", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1233, "text": "Pulmonary lymphangioleiomyomatosis is a rare cause of recurrent pneumothorax and should be considered a differential diagnosis, especially in young women with diffuse bilateral bullous emphysema or tuberous sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14716484", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 523, "text": "The disease is characterized by the development of benign hamartomatous tumors: neurofibromas and angiofibromas, located in the skin, central nervous system, mucosas and other organs. Abnormal neural cell migration plays an important role in the neurological dysfunctions found in TS, the predominant features being mental retardation, seizures and behavioral disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12618672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The true prevalence of pulmonary lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex (TSC) is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11520735", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 300, "text": "We retrospectively reviewed a cohort of patients with TSC and refractory epilepsy who started CLB over a 5-year period. Clinical characteristics and number of tubers on MRI were assessed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23219029", "endSection": "abstract" } ] }, { "body": "What is known about MER41 repeat sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "http://www.ncbi.nlm.nih.gov/pubmed/9204548" ], "ideal_answer": [ "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu familyMER41 repeat sequences contain inducible STAT1 binding sites", "The sequences of five families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family. MER41 repeat sequences contain inducible STAT1 binding sites. The observation of the binding of activated STAT1 protein to a specific repetitive element bolsters similar reports concerning p53 and other TFs, and strengthens the notion of an involvement of repeats in gene regulation.", "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family MER41 repeat sequences contain inducible STAT1 binding sites " ], "type": "summary", "id": "55414e4f472cfd8617000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 822, "text": "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9204548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "MER41 repeat sequences contain inducible STAT1 binding sites", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "title" }, { "offsetInBeginSection": 701, "offsetInEndSection": 1973, "text": "Contrary to previous claims, we find no evidence that STAT1 binds to multiple distinct motifs upon interferon-gamma stimulation in vivo. While a large majority of genomic sites with high ChIP-seq signal is associated with a nucleotide sequence resembling a STAT1 binding site, only a very small subset of the over 5 million potential STAT1 binding sites in the human genome is covered by ChIP-seq data. Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41). The observation of the binding of activated STAT1 protein to a specific repetitive element bolsters similar reports concerning p53 and other TFs, and strengthens the notion of an involvement of repeats in gene regulation. Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents. On a methodological aspect, the presence of large numbers of nearly identical binding sites in repetitive sequences may lead to wrong conclusions about intrinsic binding preferences of TF as illustrated by the spacing analysis STAT1 tandem motifs. Therefore, ChIP-seq data should be analyzed independently within repetitive and non-repetitive sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "MER41 repeat sequences contain inducible STAT1 binding sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "title" }, { "offsetInBeginSection": 372, "offsetInEndSection": 508, "text": "The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9204548", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1229, "text": "Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1611, "text": "Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 511, "text": "The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9204548", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1236, "text": "Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1620, "text": "Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 510, "text": "The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9204548", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1235, "text": "Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1619, "text": "Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "endSection": "abstract" } ] }, { "body": "How functional connectivity of the default mode network changes in patients with disorders of consciousness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23034909", "http://www.ncbi.nlm.nih.gov/pubmed/22418054", "http://www.ncbi.nlm.nih.gov/pubmed/22905075", "http://www.ncbi.nlm.nih.gov/pubmed/22623966", "http://www.ncbi.nlm.nih.gov/pubmed/21693087", "http://www.ncbi.nlm.nih.gov/pubmed/21191476", "http://www.ncbi.nlm.nih.gov/pubmed/22218274", "http://www.ncbi.nlm.nih.gov/pubmed/19289479", "http://www.ncbi.nlm.nih.gov/pubmed/22039473", "http://www.ncbi.nlm.nih.gov/pubmed/22563263" ], "ideal_answer": [ "Functional connectivity in the default mode network (DMN) is reduced in patients with different disorders of consciousness, and correlates with the level of consciousness. \nSpecifically, functional connectivity in the default mode network was shown to be absent in brain death patients, extremely low in vegetative state patients and slightly decreased in minimally conscious state patients when compared to healthy subjects. Therefore, functional connectivity in the default mode network was suggested to be valuable in differentiating patients with different disorders of consciousness. Clinically, functional connectivity in the default mode network was also shown to be an indicator of the extent of cortical disruption and predict reversible impairments in consciousness." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059907", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009415", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003244" ], "type": "summary", "id": "514a2649d24251bc0500005a", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 196, "text": "Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034909", "endSection": "sections.0" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1167, "text": "Patients showed significant impairments in all of the pathways connecting cortical regions within this network, as well as the pathway connecting the posterior cingulate cortex/precuneus with the thalamus, relative to the healthy volunteers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034909", "endSection": "sections.0" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1476, "text": "Moreover, the structural integrity of this pathway, as well as that of those connecting the posterior areas of the network, was correlated with the patients' behavioral signs for awareness, being higher in EMCS patients than those in the upper and lower ranges of the MCS patients, and lowest in VS patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034909", "endSection": "sections.0" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 1719, "text": "These results provide a possible neural substrate for the functional disconnection previously described in these patients, and reinforce the importance of the DMN in the genesis of awareness and the neural bases of its disorders.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034909", "endSection": "sections.0" }, { "offsetInBeginSection": 193, "offsetInEndSection": 394, "text": "Although the functional significance of the default-mode network remains a matter of debate, it has been suggested to be a candidate for the network subserving basic functions related to consciousness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22418054", "endSection": "sections.0" }, { "offsetInBeginSection": 510, "offsetInEndSection": 842, "text": "Despite resolution of corpus callosum lesion on magnetic resonance imaging (MRI) within 1 week, the patient persistently presented disturbance of consciousness. Resting-state functional MRI revealed that the posterior cingulate cortex/precuneus was functionally disconnected from other brain regions within the default-mode network.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22418054", "endSection": "sections.0" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1061, "text": "Our case report suggests that assessment of the functional connectivity in the resting-state default-mode network could be a useful marker of consciousness disturbance even in the presence of a reversible brain lesion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22418054", "endSection": "sections.0" }, { "offsetInBeginSection": 487, "offsetInEndSection": 666, "text": "A present and intact DMN was observed in controls and those patients who subsequently regained consciousness, but was disrupted in all patients who failed to regain consciousness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22218274", "endSection": "sections.0" }, { "offsetInBeginSection": 680, "offsetInEndSection": 770, "text": "The results suggest that the DMN is necessary but not sufficient to support consciousness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22218274", "endSection": "sections.0" }, { "offsetInBeginSection": 771, "offsetInEndSection": 915, "text": "Clinically, DMN connectivity may serve as an indicator of the extent of cortical disruption and predict reversible impairments in consciousness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22218274", "endSection": "sections.0" }, { "offsetInBeginSection": 427, "offsetInEndSection": 643, "text": "Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21693087", "endSection": "sections.0" }, { "offsetInBeginSection": 309, "offsetInEndSection": 626, "text": "This report shows for the first time, in three patients, that the persistent vegetative state (PVS) is marked by a dysfunctional default mode network, with decreased connectivity in several brain regions, including the dorsolateral prefrontal cortex and anterior cingulated cortex, especially in the right hemisphere.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289479", "endSection": "sections.0" } ] }, { "body": "Have C12orf65 mutations been associated with axonal neuropathy and optic atrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "http://www.ncbi.nlm.nih.gov/pubmed/23188110", "http://www.ncbi.nlm.nih.gov/pubmed/25519961", "http://www.ncbi.nlm.nih.gov/pubmed/24284555", "http://www.ncbi.nlm.nih.gov/pubmed/24424123" ], "ideal_answer": [ "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy", "The association of neuropathy and optic atrophy (also known as Charcot-Marie-Tooth [CMT] disease type 6) has been described with autosomal dominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, whereas a protein-truncating mutation in the C12orf65 gene, which codes for a protein involved in mitochondrial translation, was found to be the cause of an autosomal recessive form of the disease, with childhood onset neuropathy and optic atrophy." ], "exact_answer": "yes", "type": "yesno", "id": "5713c7dd1174fb1755000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 1031, "text": "Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, but until now, mutations in the recessive forms of disease have never been identified.METHODS: We here describe a family with three affected individuals who inherited in an autosomal recessive fashion a childhood onset neuropathy and optic atrophy. Using homozygosity mapping in the family and exome sequencing in two affected individuals we identified a novel protein-truncating mutation in the C12orf65 gene, which encodes for a protein involved in mitochondrial translation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "title" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1553, "text": "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 475, "text": "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23188110", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24284555", "endSection": "title" }, { "offsetInBeginSection": 526, "offsetInEndSection": 712, "text": "Recently, we identified the causative gene, C12orf65, that was reported the gene for Leigh syndrome, for autosomal recessive spastic paraplegia with optic atrophy and neuropathy (SPG55).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25519961", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 705, "text": "We describe 2 siblings with compound heterozygous mutations in the recently identified C12orf65 gene who presented with optic atrophy and mild developmental delays and subsequently developed bilateral, symmetric lesions in the brainstem reminiscent of Leigh syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24284555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 474, "text": "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1386, "text": "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 1574, "offsetInEndSection": 1759, "text": "CONCLUSIONS: This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 476, "text": "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1382, "text": "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1264, "text": "We described a large consanguineous family with neuropathy and optic atrophy carrying a loss of function mutation in the C12orf65 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1381, "text": "In these patients, we identified a homozygous splice mutation, g.21043\u2009T>A (c.282+2\u2009T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1717, "text": "This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "abstract" }, { "offsetInBeginSection": 1205, "offsetInEndSection": 1382, "text": "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "title" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1721, "text": "This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23188110", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 476, "text": "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "endSection": "abstract" } ] }, { "body": "List drugs included in the DHAP-R chemotherapy regiment.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22136378", "http://www.ncbi.nlm.nih.gov/pubmed/20709662", "http://www.ncbi.nlm.nih.gov/pubmed/21947824", "http://www.ncbi.nlm.nih.gov/pubmed/19406729", "http://www.ncbi.nlm.nih.gov/pubmed/12478903", "http://www.ncbi.nlm.nih.gov/pubmed/23692856", "http://www.ncbi.nlm.nih.gov/pubmed/20660832", "http://www.ncbi.nlm.nih.gov/pubmed/23233612", "http://www.ncbi.nlm.nih.gov/pubmed/16702182", "http://www.ncbi.nlm.nih.gov/pubmed/21656329", "http://www.ncbi.nlm.nih.gov/pubmed/17971487" ], "ideal_answer": [ "Dexamethasone (a steroid hormone), cytarabine (ara-C), cisplatin (platinum agent) and rituximab are included in the DHAP-R chemotherapy protocol." ], "exact_answer": [ [ "dexamethasone" ], [ "cytarabine" ], [ "cisplatin" ], [ "rituximab" ] ], "type": "list", "id": "54f0920f94afd61504000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Standard treatment of transplant-eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL) consists of rituximab and platinum-based chemotherapy, either ifosfamide, carboplatin, and etoposide (ICE) or dexamethasone, cytarabine, and cisplatin (DHAP), with autologous transplant consolidation for those with chemosensitive disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692856", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 698, "text": "The intergroup Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) set the limits for this standard of treatment after first comparing 2 salvage regimens: rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) and rituximab, dexamethasone, aracytine, and cisplatin (R-DHAP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23233612", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 810, "text": "The response rate (RR) to first salvage chemotherapy was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP] 15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients underwent ASCT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "PURPOSE: To evaluate the prognostic value of the cell of origin (COO) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBLC), prospectively treated by rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) versus rituximab, ifosfamide, carboplatin, and etoposide and followed by intensive therapy plus autologous stem-cell transplantation on the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "The aim of this study was to evaluate the efficacy and toxicity of two chemotherapy regimens based on platinum and cytarabine in association with etoposide and methylprednisolone (ESHAP) or with dexamethasone (DHAP) with or without Rituximab (\u00b1 R) in patients with refractory or a relapsed Primary Central Nervous System Lymphoma (PCNSL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21656329", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 307, "text": "R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20709662", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 557, "text": "PATIENTS AND METHODS: Patients with CD20(+) DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20660832", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 759, "text": "Because of the inability to safely administer unattenuated doses of anthracycline-based regimens, dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was used at full doses (along with rituximab for the DLBCL patient) until hepatic function normalized (1-5 cycles). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19406729", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 471, "text": "Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17971487", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 393, "text": "Patients are first randomised between ICE (ifosfamide, carboplatin, etoposide) and DHAP (dexamethasone, ara-C and cisplatin), both combined with rituximab (R-ICE or R-DHAP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "BACKGROUND AND OBJECTIVE: The treatment of the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL) remains difficult. It was reported that DHAP regimen(cisplatin + Ara-C + dexamthsone) was an effective salvage therapy, but there was no report about it in China. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12478903", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 470, "text": "Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17971487", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 469, "text": "Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17971487", "endSection": "abstract" } ] }, { "body": "Are psammoma bodies characteristic to meningiomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2168257", "http://www.ncbi.nlm.nih.gov/pubmed/8162148", "http://www.ncbi.nlm.nih.gov/pubmed/3020860", "http://www.ncbi.nlm.nih.gov/pubmed/8336812", "http://www.ncbi.nlm.nih.gov/pubmed/3776472", "http://www.ncbi.nlm.nih.gov/pubmed/8712177", "http://www.ncbi.nlm.nih.gov/pubmed/8629394", "http://www.ncbi.nlm.nih.gov/pubmed/19373908", "http://www.ncbi.nlm.nih.gov/pubmed/1492779", "http://www.ncbi.nlm.nih.gov/pubmed/3736772", "http://www.ncbi.nlm.nih.gov/pubmed/6699695", "http://www.ncbi.nlm.nih.gov/pubmed/7015802", "http://www.ncbi.nlm.nih.gov/pubmed/10396741", "http://www.ncbi.nlm.nih.gov/pubmed/1630573", "http://www.ncbi.nlm.nih.gov/pubmed/7487408", "http://www.ncbi.nlm.nih.gov/pubmed/8727067" ], "ideal_answer": [ "Yes, psammoma bodies are commonly seen and are characteristic to meningiomas. However, they can be also present in other types of tumors or non-neoplastic tissues." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:7210", "http://www.disease-ontology.org/api/metadata/DOID:3565", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002479", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579" ], "type": "yesno", "id": "514a4679d24251bc0500005b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Psammoma bodies (PBs) are concentric lamellated calcified structures, observed most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of ovary but have rarely been reported in other neoplasms and nonneoplastic lesions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19373908", "endSection": "sections.0" }, { "offsetInBeginSection": 668, "offsetInEndSection": 863, "text": "Studies on serous cystadenocarcinoma of ovary and meningioma, however, revealed that collagen production by neoplastic cells and subsequent calcification was responsible for the formation of PBs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19373908", "endSection": "sections.0" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1163, "text": "The existence of some precursor forms of PBs was reported in meningiomas and more recently in PTC, which were mostly in the form of extracellular hyaline globules surrounded by well-preserved neoplastic cells or in a smaller number of cases intracytoplasmic bodies liberated from intact tumor cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19373908", "endSection": "sections.0" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1677, "text": "Light microscopy revealed abundant microcysts of varied size throughout the tumor tissue with the presence of whorl formation and psammoma body, but no malignancy was indicated. Electron microscopy further demonstrated interdigitation of the neighboring cell membranes, desmosomes, and intracytoplasmic filaments, which are pathognomonic findings of meningiomas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10396741", "endSection": "sections.0" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1531, "text": "Unlike SFT, FMs were glycogen-containing and variously exhibited a storiform pattern (13 of 20), psammoma body formation (9 of 20), and calcification of collagen (4 of 20). Immunoreactivities included vimentin (100%), focal to patchy EMA (80%), S-100 protein (80%), collagen IV (25%), and patchy, mild-to-moderate CD34 staining (60%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8712177", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "In contrast to the inner structure, three-dimensional structure of psammona bodies in meningiomas is not well defined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8727067", "endSection": "sections.0" }, { "offsetInBeginSection": 119, "offsetInEndSection": 337, "text": "This study examined three cultured meningiomas, in which surface observation of psammoma bodies might be easier than in the tumor tissues since influence of interposing connective tissue is minimized in tissue culture.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8727067", "endSection": "sections.0" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1284, "text": "The results suggest that psammoma bodies in meningiomas arise in part from meningothelial whorls due to collagen production by tumor cells followed by obliteration and disappearance of tumor cell processes, although some of the alternative pathways for psammoma body formation proposed by other investigators cannot be ruled out by this study.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8727067", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 105, "text": "To demonstrate that psammoma bodies in human meningiomas contain type VI collagen and laminin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8629394", "endSection": "sections.0" }, { "offsetInBeginSection": 690, "offsetInEndSection": 818, "text": "This is the first report to describe the involvement of type VI collagen in psammoma bodies and whorl formations in meningiomas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8629394", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Calcification such as psammoma body is sometimes found especially in spinal cord meningioma but ossification of the meningeal tumor was rarely observed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8162148", "endSection": "sections.0" }, { "offsetInBeginSection": 603, "offsetInEndSection": 673, "text": "Histological diagnosis was transitional meningioma with psammoma body.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8336812", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "In this study we analyzed the morphologic and ultrastructural characteristics of the psammoma bodies in ten meningiomas of different histologic subtypes, characterizing the components of the psammoma body and the elements of the tumor, such as the capillaries and degenerative cells that have been classically considered as initiators of the formation of these calcareous is structures.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1492779", "endSection": "sections.0" }, { "offsetInBeginSection": 735, "offsetInEndSection": 979, "text": "It is concluded that the mineralization of the psammoma bodies is induced principally by the collagen fibers synthesized by the meningocytes and that the form of mineralization is spherical and growth is radial, controlled by the tumoral cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1492779", "endSection": "sections.0" }, { "offsetInBeginSection": 495, "offsetInEndSection": 610, "text": "CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1630573", "endSection": "sections.0" }, { "offsetInBeginSection": 568, "offsetInEndSection": 743, "text": "Electron microscopic examination of the calculi showed membrane-bound vesicles and radially precipitated crystals that simulated hydroxyapatite of psammoma body in meningioma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2168257", "endSection": "sections.0" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1291, "text": "Psammoma bodies in meningiomas resembled those in the choroid plexus stroma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3736772", "endSection": "sections.0" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1626, "text": "The results of this study suggest that psammoma bodies in the choroid plexus, as in meningiomas, form by a process of dystrophic calcification associated with arachnoid cells and collagen fibres.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3736772", "endSection": "sections.0" }, { "offsetInBeginSection": 257, "offsetInEndSection": 384, "text": "An early stage of psammoma body formation was seen more frequently in these villous microcores than in the meningocytic whorls.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3776472", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Psammoma bodies in meningocytic whorls were investigated by electron microscopy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3020860", "endSection": "sections.0" }, { "offsetInBeginSection": 800, "offsetInEndSection": 1011, "text": "Psammoma body formation in the meningocytic whorls may represent degeneration in some whorls of the central cells which contain connective tissue fibers, producing cell debris such as membrane invested vesicles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3020860", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Twenty human meningiomas were examined for IgG and IgM by the direct immunofluorescence of immunoperoxidase methods, or both. IgG was conspicuously found in and around the blood vessels, whorls, and psammoma bodies. It was also clearly present on the cytoplasmic membranes of the tumour cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7015802", "endSection": "sections.0" }, { "offsetInBeginSection": 357, "offsetInEndSection": 514, "text": "Significance of these findings is briefly discussed including possible humoral immune reactions in regard to whorl and psammoma body formation in meningioma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7015802", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "The fine structure of psammoma bodies was examined in four cases of fibroblastic meningioma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6699695", "endSection": "sections.0" }, { "offsetInBeginSection": 93, "offsetInEndSection": 216, "text": "In general, large numbers of various-sized calcified bodies (psammoma bodies) were scattered among the interstitial fibers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6699695", "endSection": "sections.0" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1293, "text": "These findings suggest that both matrix giant bodies and matrix vesicles may serve as initial nidus of calcification of psammoma bodies in fibroblastic meningioma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6699695", "endSection": "sections.0" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1114, "text": "Psammoma body formation or dystrophic mineralization and gliosis of the intervening parenchyma was observed in all three cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7487408", "endSection": "sections.0" } ] }, { "body": "Which are the most common symptoms in Lambert-Eaton Myasthenic Syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8505927", "http://www.ncbi.nlm.nih.gov/pubmed/16526254", "http://www.ncbi.nlm.nih.gov/pubmed/24481713", "http://www.ncbi.nlm.nih.gov/pubmed/24114606", "http://www.ncbi.nlm.nih.gov/pubmed/21822385", "http://www.ncbi.nlm.nih.gov/pubmed/18653248" ], "ideal_answer": [ "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome)", "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms, that may include dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer, and the other that is a pure autoimmune form." ], "exact_answer": [ [ "proximal limb muscle weakness" ], [ "fatigability" ], [ "decreased deep-tendon reflexes" ], [ "autonomic symptoms" ], [ "small-cell lung cancer" ] ], "type": "list", "id": "57220e400fd6f91b68000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 425, "text": "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114606", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 878, "text": "LEMS weakness typically involves lower and upper limbs and the proximal muscles are predominantly affected. A significant proportion of patients also have dysfunction of the autonomic nervous system that may include dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension. LEMS recognition is based on clinical, electrophysiological and immunological criteria. Nearly 50-60% of patients with LEMS have an underlying tumour that, in almost all cases, is a small-cell lung cancer;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24481713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "In Lambert-Eaton myasthenic syndrome (LEMS), antibodies against presynaptic voltage-gated calcium channels reduce the quantal release of acetylcholine, causing muscle weakness and autonomic dysfunction. More than half of the affected patients have associated small cell lung cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21822385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "The Lambert-Eaton myasthenic syndrome (LEMS) is a disease of neuromuscular transmission in which autoantibodies against the P/Q-type voltage-gated calcium channel (VGCC) at the presynaptic nerve terminal play a major role in decreasing quantal release of acetylcholine (ACh), resulting in skeletal muscle weakness and autonomic symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18653248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8505927", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 427, "text": " Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114606", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 634, "text": "The Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disorder, often associated with small cell lung carcinoma (SCLC), which is characterized by reduced quantal release of acetylcholine from the motor nerve terminals. LAMBERT-EATON MYASTHENIC SYNDROME: The Lambert-Eaton Myasthenic Syndrome (LEMS) is characterized by proximal muscle weakness initially affecting gait, autonomic symptoms (dry mouth, constipation, erectile failure) and augmentation of strength during initial voluntary activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16526254", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 634, "text": "LAMBERT-EATON MYASTHENIC SYNDROME: The Lambert-Eaton Myasthenic Syndrome (LEMS) is characterized by proximal muscle weakness initially affecting gait, autonomic symptoms (dry mouth, constipation, erectile failure) and augmentation of strength during initial voluntary activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16526254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8505927", "endSection": "title" } ] }, { "body": "What is the pyroptotic pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21057511", "http://www.ncbi.nlm.nih.gov/pubmed/25043180", "http://www.ncbi.nlm.nih.gov/pubmed/21178113", "http://www.ncbi.nlm.nih.gov/pubmed/24667705", "http://www.ncbi.nlm.nih.gov/pubmed/25341033", "http://www.ncbi.nlm.nih.gov/pubmed/24376002", "http://www.ncbi.nlm.nih.gov/pubmed/23816851", "http://www.ncbi.nlm.nih.gov/pubmed/26056317", "http://www.ncbi.nlm.nih.gov/pubmed/25418070", "http://www.ncbi.nlm.nih.gov/pubmed/23637985" ], "ideal_answer": [ "Pyroptosis is an inflammasome-mediated programmed cell death pathway." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:649", "http://www.disease-ontology.org/api/metadata/DOID:12858", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069292", "http://www.disease-ontology.org/api/metadata/DOID:6576", "http://www.disease-ontology.org/api/metadata/DOID:1393", "http://www.disease-ontology.org/api/metadata/DOID:6575" ], "type": "summary", "id": "56afa7fd0a360a5e45000016", "snippets": [ { "offsetInBeginSection": 1036, "offsetInEndSection": 1058, "text": "pyroptotic cell death,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26056317", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 655, "text": " pyroptotic cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23816851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Pyroptosis is an inflammasome-mediated programmed cell death pathway triggered in macrophages by a variety of stimuli, including intracellular bacterial pathogens. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24376002", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 761, "text": "pyroptotic death ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25043180", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 402, "text": "C. albicans triggers pyroptosis, a proinflammatory macrophage death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25418070", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 230, "text": "associated with pyroptosis, the pro-inflammatory programmed cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25341033", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 880, "text": "Our study here identified a novel cell death, pyroptosis in ox-LDL induced human macrophage, which may be implicated in lesion macrophages death and play an important role in lesion instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23637985", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 584, "text": "pyroptotic cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21178113", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 508, "text": " caspase-1-induced pyroptotic cell death ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21057511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21057511", "endSection": "title" } ] }, { "body": "Which types of bacterial microflora are associated with the progression of peri-implantitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20976394", "http://www.ncbi.nlm.nih.gov/pubmed/9526919", "http://www.ncbi.nlm.nih.gov/pubmed/14598129", "http://www.ncbi.nlm.nih.gov/pubmed/23937262" ], "ideal_answer": [ "Bacteria such as A. actinomycetemcomitans, P. gingivalis, T. forsythensis, T. denticola, P. intermedia and F. nucleatum are associated with the progression of peri-implantitis." ], "exact_answer": [ [ "A. actinomycetemcomitans" ], [ "P. gingivalis" ], [ "T. denticola" ], [ "T. forsythia" ], [ "P. intermedia" ], [ "F. nucleatum" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057873" ], "type": "list", "id": "553babc0f321868558000007", "snippets": [ { "offsetInBeginSection": 522, "offsetInEndSection": 758, "text": " Later, the specific plaque hypothesis established the role of some microorganisms such as A. actinomycetemcomitans, P. gingivalis, T. forsythensis, T. denticola, P. intermedia and F. nucleatum in different forms of periodontal diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20976394", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1259, "text": "The microbiological analysis revealed that the total bacterial load increased during the period following ligature removal and established an anaerobic Gram-negative microflora.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23937262", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 681, "text": "Most periodontal pathogens are common saprophytes of the oral cavity, expressing their virulence only in a susceptible host or when some changes come about in the oral environment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14598129", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 1013, "text": "Overall, the types and relative proportions of putative periodontal pathogens in plaque associated with ligature-induced peri-implantitis and ligature-induced periodontitis were similar. Only levels of anaerobic Actinomyces and spirochetes were significantly different between both sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9526919", "endSection": "abstract" } ] }, { "body": "What are the known families of deadenylases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19605561", "http://www.ncbi.nlm.nih.gov/pubmed/11239395", "http://www.ncbi.nlm.nih.gov/pubmed/22442711", "http://www.ncbi.nlm.nih.gov/pubmed/12590136", "http://www.ncbi.nlm.nih.gov/pubmed/22817748", "http://www.ncbi.nlm.nih.gov/pubmed/23337855", "http://www.ncbi.nlm.nih.gov/pubmed/15769875", "http://www.ncbi.nlm.nih.gov/pubmed/21743004", "http://www.ncbi.nlm.nih.gov/pubmed/20628353", "http://www.ncbi.nlm.nih.gov/pubmed/12844354", "http://www.ncbi.nlm.nih.gov/pubmed/11747467", "http://www.ncbi.nlm.nih.gov/pubmed/21245038", "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "http://www.ncbi.nlm.nih.gov/pubmed/19955262", "http://www.ncbi.nlm.nih.gov/pubmed/17766253", "http://www.ncbi.nlm.nih.gov/pubmed/11889047", "http://www.ncbi.nlm.nih.gov/pubmed/14618157", "http://www.ncbi.nlm.nih.gov/pubmed/23274303", "http://www.ncbi.nlm.nih.gov/pubmed/15044470", "http://www.ncbi.nlm.nih.gov/pubmed/19276069", "http://www.ncbi.nlm.nih.gov/pubmed/22073225", "http://www.ncbi.nlm.nih.gov/pubmed/21965533" ], "triples": [ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51354137363100D", "o": "Cytoplasmic deadenylase" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_443256444B36007", "o": "mRNA deadenylase" } ], "ideal_answer": [ "All known deadenylases belong to either the DEDD or the exonuclease\u2013endonuclease\u2013phosphatase (EEP) superfamily. Members of DEDD include the POP2, CAF1Z, PARN and PAN2 families. Members of EEP include the CCR4, Nocturnin, ANGEL and 2'-PDE families." ], "exact_answer": [ [ "POP2" ], [ "CAF1Z" ], [ "PARN" ], [ "PAN2" ], [ "CCR4" ], [ "Nocturnin" ], [ "ANGEL" ], [ "2'-PDE" ] ], "type": "list", "id": "5162c8a8298dcd4e51000047", "snippets": [ { "offsetInBeginSection": 157, "offsetInEndSection": 377, "text": "Among the deadenylase family, poly(A)-specific ribonuclease (PARN) is unique in its domain composition, which contains three potential RNA-binding domains: the catalytic nuclease domain, the R3H domain and the RRM domain", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "endSection": "sections.0" }, { "offsetInBeginSection": 813, "offsetInEndSection": 1090, "text": "On the other hand, the interaction between CNOT7 and BTG2, a member of the antiproliferative BTG/Tob family involved in transcription and mRNA decay appears less important for proliferation of MCF7 cells, suggesting that CNOT7 does not function solely in conjunction with BTG2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19605561", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "The Tob/BTG family is a group of antiproliferative proteins containing two highly homologous regions, Box A and Box B. These proteins all associate with CCR4-associated factor 1 (Caf1), which belongs to the ribonuclease D (RNase D) family of deadenylases and is a component of the CCR4-Not deadenylase complex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276069", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The CCR4 family proteins are 3'-5'-deadenylases that function in the first step of the degradation of poly(A) mRNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12590136", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "CCR4, an evolutionarily conserved member of the CCR4-NOT complex, is the main cytoplasmic deadenylase. It contains a C-terminal nuclease domain with homology to the endonuclease-exonuclease-phosphatase (EEP) family of enzymes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20628353", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The yeast Pop2 protein, belonging to the eukaryotic Caf1 family, is required for mRNA deadenylation in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15769875", "endSection": "sections.0" }, { "offsetInBeginSection": 178, "offsetInEndSection": 308, "text": "Although CAF1 protein belongs to the DEDDh family of RNases, CCR4 appears to be the principle deadenylase of the CCR4-NOT complex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15044470", "endSection": "sections.0" }, { "offsetInBeginSection": 417, "offsetInEndSection": 630, "text": "Like CCR4, increased length of RNA substrates converted mCAF1 into a processive enzyme. In contrast to two other DEDD family members, PAN2 and PARN, mCAF1 was not activated either by PAB1 or capped RNA substrates.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15044470", "endSection": "sections.0" }, { "offsetInBeginSection": 346, "offsetInEndSection": 462, "text": "The domain has the fold of the DnaQ family and represents the first structure of an RNase from the DEDD superfamily.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14618157", "endSection": "sections.0" }, { "offsetInBeginSection": 253, "offsetInEndSection": 452, "text": "The evolutionarily conserved CCR4 protein, which is part of the cytoplasmic deadenylase, contains a C-terminal domain that displays homology to an Mg2+-dependent DNase/phosphatase family of proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11889047", "endSection": "sections.0" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1219, "text": "These results establish that CCR4 and most probably other members of a widely distributed CCR4-like family of proteins constitute a novel class of RNA-DNA exonucleases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11889047", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Deadenylases specifically catalyze the degradation of eukaryotic mRNA poly(A) tail in the 3'- to 5'-end direction with the release of 5'-AMP as the product.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Shortening and removal of the 3' poly(A) tail of mature mRNA by poly(A)-specific 3' exonucleases (deadenylases) is the initial and often rate-limiting step in mRNA degradation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23337855", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "PARN, Nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23274303", "endSection": "sections.0" } ] }, { "body": "Which translocation is harbored in the Askin tumor cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7591257", "http://www.ncbi.nlm.nih.gov/pubmed/17009618", "http://www.ncbi.nlm.nih.gov/pubmed/2162733", "http://www.ncbi.nlm.nih.gov/pubmed/1333942", "http://www.ncbi.nlm.nih.gov/pubmed/3004699", "http://www.ncbi.nlm.nih.gov/pubmed/7571088", "http://www.ncbi.nlm.nih.gov/pubmed/9213191", "http://www.ncbi.nlm.nih.gov/pubmed/23674776" ], "ideal_answer": [ "The Askin tumor is a primitive malignant small-cell tumor of the chest wall mostly seen among children and adolescents. It is closely related to Ewing's sarcoma of the same location, with both tumors harboring reciprocal translocation t(11;22) (q24;q12)." ], "exact_answer": [ "reciprocal translocation t(11;22) (q24;q12)" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050608" ], "type": "factoid", "id": "553656c4bc4f83e828000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "The Ewing sarcoma family of tumors includes osseous Ewing sarcoma, extraskeletal Ewing sarcoma, primitive neuroectodermal tumor, and Askin tumor. They share a karyotype abnormality with translocation involving chromosomes 11 and 22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23674776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Ewing tumor family consists of Ewing tumor of bone, extraosseous Ewing tumor, primitive neurectodermal tumor and Askin tumor. All of them share genetic abnormality, reciprocal translocation (11; 22) (q24; q12), and originate from the same primordial stem cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17009618", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 551, "text": "Chromosomal analysis of the neoplastic cells revealed translocation (11;22)(q24;q12), which is often found in Ewing's sarcoma and Askin tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9213191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Malignant small cell tumor of the thoracopulmonary region (MSCT) was first described in 1979 and has been referred to as the Askin tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7571088", "endSection": "abstract" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1454, "text": "MSCT and PPNET have a common reciprocal cytogenetic translocation [t(11;22)q(24;q12)], which is shared with Ewing's sarcoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7571088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "The Askin tumor, a primitive malignant small-cell tumor of the chest wall, is mostly seen among children and adolescents. It is closely related to Ewing's sarcoma of the same location, both tumors showing a chromosomal translocation t(11;22)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1333942", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 548, "text": "Chromosomal analysis of the neoplastic cells revealed translocation (11;22)(q24;q12), which is often found in Ewing's sarcoma and Askin tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9213191", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 552, "text": "Chromosomal analysis of the neoplastic cells revealed translocation (11;22)(q24;q12), which is often found in Ewing's sarcoma and Askin tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9213191", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 778, "text": "In Ewing's sarcoma (a tumor of unknown histogenesis), and in peripheral neuroepithelioma and Askin's tumor (tumors with evidence of neural origin), we have observed an indistinguishable t(11;22) translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3004699", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 366, "text": "Reciprocal translocations of chromosomes 11 and 22 are the most common cytogenetic abnormalities in Ewing's sarcoma and the related Askin's tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2162733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The t(11;22)(q24;q12) and t(21;22)(q22;q12) are specific chromosomal translocations found in the Ewing family of tumors including ES, PNET and Askin tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7591257", "endSection": "abstract" } ] }, { "body": "What is the function of the AtxA pleiotropic regulator?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14702298", "http://www.ncbi.nlm.nih.gov/pubmed/21911592", "http://www.ncbi.nlm.nih.gov/pubmed/19651859", "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "http://www.ncbi.nlm.nih.gov/pubmed/18676674", "http://www.ncbi.nlm.nih.gov/pubmed/22636778", "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "http://www.ncbi.nlm.nih.gov/pubmed/17302796", "http://www.ncbi.nlm.nih.gov/pubmed/20863885", "http://www.ncbi.nlm.nih.gov/pubmed/10361306", "http://www.ncbi.nlm.nih.gov/pubmed/9119194", "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "http://www.ncbi.nlm.nih.gov/pubmed/17302798" ], "ideal_answer": [ "AtxA is the gene encoding the trans-activator of anthrax toxin synthesis and is essential for virulence of B. anthracis. It is located on the resident 185-kb plasmid pXO1 and its activation is stimulated by bicarbonate. AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air. Dual promoters control expression of AtxA. Transcription of the atxA gene occurs from two independent promoters, P1 and P2, whose transcription start sites are separated by 650 bp.", "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. The AtxA virulence regulator of Bacillus anthracis is required for toxin and capsule gene expression. DNA sequence analysis of transposon insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed 10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which did not map to the toxin genes. We purified histidine-tagged AtxA [AtxA(His)] from Escherichia coli and used anti-AtxA(His) serum to detect AtxA in protein preparations from B. anthracis cells.", "The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence." ], "concepts": [ "http://www.biosemantics.org/jochem#4244018", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001408" ], "type": "summary", "id": "5710a51bcf1c325851000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "endSection": "title" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1322, "text": "The atxA-null mutant is avirulent in mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1546, "text": "These data suggest that the atxA gene product also regulates toxin gene expression during infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 716, "text": "Thus, we conclude that the pX01 influence on capsule synthesis is mediated by AtxA, the pXO1-encoded trans-activator of the toxin gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9119194", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 138, "text": "atxA, the gene encoding the trans-activator of anthrax toxin synthesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "title" }, { "offsetInBeginSection": 189, "offsetInEndSection": 385, "text": "The genes atxA, located on pXO1, and acpA, located on pXO2, encode positive trans-acting proteins that are involved in bicarbonate-mediated regulation of toxin and capsule production, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1580, "text": " Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 342, "text": "In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "abstract" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1648, "text": "Our data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "endSection": "abstract" }, { "offsetInBeginSection": 1623, "offsetInEndSection": 1819, "text": " Our data strongly suggest that an additional factor(s) is involved in regulation of pag and that the relative amounts of such a factor(s) and AtxA are important for optimal toxin gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Two regulatory genes, acpA and atxA, have been reported to control expression of the Bacillus anthracis capsule biosynthesis operon capBCAD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14702298", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 238, "text": "The atxA gene is located on the virulence plasmid pXO1, while pXO2 carries acpA and the cap genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14702298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Dual promoters control expression of the Bacillus anthracis virulence factor AtxA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18676674", "endSection": "title" }, { "offsetInBeginSection": 273, "offsetInEndSection": 554, "text": "Here we report that transcription of the atxA gene occurs from two independent promoters, P1 (previously described by Dai et al. [Z. Dai, J. C. Sirard, M. Mock, and T. M. Koehler, Mol. Microbiol. 16:1171-1181, 1995]) and P2, whose transcription start sites are separated by 650 bp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18676674", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 379, "text": "AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20863885", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 1012, "text": "Here we employ 5' and 3' deletion analysis and site-directed mutagenesis of the atxA control region to demonstrate that atxA transcription from the major start site P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA and an A+T-rich upstream element for RNA polymerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22636778", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1262, "text": "We also show that an additional trans-acting protein(s) binds specifically to atxA promoter sequences located between -13 and +36 relative to P1 and negatively impacts transcription. Deletion of this region increases promoter activity up to 15-fold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22636778", "endSection": "abstract" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1786, "text": "A majority of genes on the virulence plasmid pXO1 that are regulated by the presence of either CO2 or AtxA separately are also regulated synergistically in the presence of both. These results also elucidate novel pXO1-encoded small RNAs that are associated with virulence conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 388, "text": "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2 through an AtxA-dependent mechanism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "title" }, { "offsetInBeginSection": 878, "offsetInEndSection": 1169, "text": "The majority of the regulated genes responded to both AtxA and carbon dioxide rather than to just one of these factors. Interestingly, we identified two previously unrecognized small RNAs that are highly expressed under physiological carbon dioxide concentrations in an AtxA-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 476, "text": "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1068, "text": "As a similar organization is found in transcription regulators in many other pathogens, AtxA might become the paradigm of a new class of virulence regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "AtxA, a Bacillus anthracis global virulence regulator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20863885", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "endSection": "title" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1208, "text": "The accumulation of the global virulence regulator AtxA protein was strongly reduced in the mutant strain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19651859", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 375, "text": "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 389, "text": "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Opposing effects of histidine phosphorylation regulate the AtxA virulence transcription factor in Bacillus anthracis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302798", "endSection": "title" }, { "offsetInBeginSection": 73, "offsetInEndSection": 231, "text": "The B. anthracis pleiotropic regulator CodY activates toxin gene expression by post-translationally regulating the accumulation of the global regulator AtxA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21911592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Cross-talk to the genes for Bacillus anthracis capsule synthesis by atxA, the gene encoding the trans-activator of anthrax toxin synthesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 348, "text": "Consistent with the role of atxA in virulence factor expression, a B. anthracis atxA-null mutant is avirulent in a murine model for anthrax. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22636778", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 377, "text": "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "endSection": "abstract" }, { "offsetInBeginSection": 1782, "offsetInEndSection": 1941, "text": "PlcR is the first example described of a pleiotropic regulator involved in the control of extracellular virulence factor expression in pathogenic Bacillus spp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10361306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "endSection": "abstract" } ] }, { "body": "Is cystatin C or cystatin 3 used as a biomarker of kidney function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23698027", "http://www.ncbi.nlm.nih.gov/pubmed/23910705", "http://www.ncbi.nlm.nih.gov/pubmed/24114579", "http://www.ncbi.nlm.nih.gov/pubmed/24001705", "http://www.ncbi.nlm.nih.gov/pubmed/23577724", "http://www.ncbi.nlm.nih.gov/pubmed/23813702", "http://www.ncbi.nlm.nih.gov/pubmed/23571811", "http://www.ncbi.nlm.nih.gov/pubmed/24178972", "http://www.ncbi.nlm.nih.gov/pubmed/24262510", "http://www.ncbi.nlm.nih.gov/pubmed/23797027", "http://www.ncbi.nlm.nih.gov/pubmed/23574755", "http://www.ncbi.nlm.nih.gov/pubmed/23701892", "http://www.ncbi.nlm.nih.gov/pubmed/24300829", "http://www.ncbi.nlm.nih.gov/pubmed/23669156", "http://www.ncbi.nlm.nih.gov/pubmed/23866593", "http://www.ncbi.nlm.nih.gov/pubmed/23744636", "http://www.ncbi.nlm.nih.gov/pubmed/24321840" ], "ideal_answer": [ "Yes, cystatin C (CysC) is a novel biomarker of renal function." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/CYT_COTJA", "http://www.uniprot.org/uniprot/CYTC_SAISC", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0065009", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003014", "http://www.uniprot.org/uniprot/CYTC_RAT", "http://www.uniprot.org/uniprot/CYTC_HUMAN", "http://www.uniprot.org/uniprot/CYT_CHICK", "http://www.uniprot.org/uniprot/CYTC_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055316", "http://www.uniprot.org/uniprot/CYT_NAJAT", "http://www.uniprot.org/uniprot/CYT_SOYBN", "http://www.biosemantics.org/jochem#4262069", "http://www.uniprot.org/uniprot/CYT_ONCKE", "http://www.uniprot.org/uniprot/CYTC_MACMU", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054316", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003674", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090183", "http://www.uniprot.org/uniprot/CYTC_RABIT" ], "type": "yesno", "id": "550bf315c2af5d5b7000000e", "snippets": [ { "offsetInBeginSection": 23, "offsetInEndSection": 202, "text": "to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321840", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1315, "text": "Cystatin C, a more specific kidney function biomarker, was also elevated at 24 h after CLP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24300829", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 454, "text": "This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24262510", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 856, "text": "he primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24178972", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 169, "text": "A number of recent reports have suggested that the cystatin C/creatinine (CysC/Cr) ratio might be a useful biomarker of renal function in pediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114579", "endSection": "abstract" }, { "offsetInBeginSection": 1653, "offsetInEndSection": 1784, "text": "The CKD-EPI equation using cystatin C was the most precise method of renal function evaluation in patients with neurogenic bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24001705", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 140, "text": "Serum cystatin C (CysC) is an endogenous marker of kidney function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23910705", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1684, "text": "The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23866593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Estimated kidney function based on serum cystatin C ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23813702", "endSection": "title" }, { "offsetInBeginSection": 15, "offsetInEndSection": 144, "text": ": Several formulas for glomerular filtration rate (GFR) estimation, based on serum creatinine or cystatin C, have been proposed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23797027", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 946, "text": "he highest and lowest eGFR levels corresponded to the cystatin C-based and MDRD-4 equations, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23797027", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 336, "text": "The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23744636", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 368, "text": "Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23701892", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 99, "text": "Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23698027", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 132, "text": "Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23669156", "endSection": "abstract" }, { "offsetInBeginSection": 1564, "offsetInEndSection": 1725, "text": " Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m(2), which also predicts the development of AKI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23577724", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 249, "text": " Cystatin C was recently reported to be an endogenous surrogate of kidney function, and a high level of cystatin C is reported to be a strong predictor of CVD;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574755", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 509, "text": "Studies that have simultaneously compared measured GFR and estimated GFR (using endogenous filtration markers such as creatinine, or newer ones such as cystatin C or \u03b2-trace protein)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23571811", "endSection": "abstract" } ] }, { "body": "Which R/bioconductor package utilizes the Hilbert curve in order to visualize genomic data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19297348" ], "ideal_answer": [ "The so-called Hilbert curve visualization can complement genome browsers and help to get further insights into the structure of one's data. An open-source application, called HilbertVis, has been developed for R/bioconductor that allows the user to produce and interactively explore such plots." ], "exact_answer": [ "HilbertVis" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ], "type": "factoid", "id": "56bdcc4cef6e394741000002", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 648, "text": "In many genomic studies, one works with genome-position-dependent data, e.g. ChIP-chip or ChIP-Seq scores. Using conventional tools, it can be difficult to get a good feel for the data, especially the distribution of features. This article argues that the so-called Hilbert curve visualization can complement genome browsers and help to get further insights into the structure of one's data. This is demonstrated with examples from different use cases. An open-source application, called HilbertVis, is presented that allows the user to produce and interactively explore such plots.AVAILABILITY: http://www.ebi.ac.uk/huber-srv/hilbert/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297348", "endSection": "abstract" } ] }, { "body": "Can fetal aneuploidy be detected with non-invasive prenatal testing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23765643", "http://www.ncbi.nlm.nih.gov/pubmed/25044397", "http://www.ncbi.nlm.nih.gov/pubmed/23712453", "http://www.ncbi.nlm.nih.gov/pubmed/24603453", "http://www.ncbi.nlm.nih.gov/pubmed/25543032", "http://www.ncbi.nlm.nih.gov/pubmed/23553438", "http://www.ncbi.nlm.nih.gov/pubmed/21076134", "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "http://www.ncbi.nlm.nih.gov/pubmed/21749753", "http://www.ncbi.nlm.nih.gov/pubmed/23299662", "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "http://www.ncbi.nlm.nih.gov/pubmed/24783433", "http://www.ncbi.nlm.nih.gov/pubmed/26252102", "http://www.ncbi.nlm.nih.gov/pubmed/17186566", "http://www.ncbi.nlm.nih.gov/pubmed/10655451", "http://www.ncbi.nlm.nih.gov/pubmed/24352524", "http://www.ncbi.nlm.nih.gov/pubmed/25449088", "http://www.ncbi.nlm.nih.gov/pubmed/21574485", "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "http://www.ncbi.nlm.nih.gov/pubmed/24312358", "http://www.ncbi.nlm.nih.gov/pubmed/23526649", "http://www.ncbi.nlm.nih.gov/pubmed/26080919", "http://www.ncbi.nlm.nih.gov/pubmed/25478006", "http://www.ncbi.nlm.nih.gov/pubmed/24667696", "http://www.ncbi.nlm.nih.gov/pubmed/22500971", "http://www.ncbi.nlm.nih.gov/pubmed/21749752", "http://www.ncbi.nlm.nih.gov/pubmed/23089167", "http://www.ncbi.nlm.nih.gov/pubmed/26237478", "http://www.ncbi.nlm.nih.gov/pubmed/23470070", "http://www.ncbi.nlm.nih.gov/pubmed/25238658" ], "ideal_answer": [ "Yes, the non-invasive preanatal test of cell-free fetal DNA is being used for fetal aneuploidy screening." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011296" ], "type": "yesno", "id": "57136cbf1174fb1755000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Non-invasive prenatal testing with cell-free DNA: US physician attitudes toward implementation in clinical practice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526649", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 200, "text": "The aim of this study was to assess awareness, potential adoption, and current utilization of non-invasive prenatal testing (NIPT) analysis for common fetal aneuploidies among obstetricians", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23526649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Cell-free DNA has been used for fetal rhesus factor and sex determination, fetal aneuploidy screening, cancer diagnostics and monitoring, and other applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25543032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23765643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23712453", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "This study aimed to develop a single-nucleotide polymorphism-based and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23712453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Non-invasive prenatal testing for aneuploidy: current status and future prospects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23765643", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23299662", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603453", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "[Non-invasive prenatal test in the diagnosis of aneuploidy 13, 18 and 21--theoretical and practical aspects].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21574485", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "To track and analyze two false positive cases from non-invasive prenatal testing for potential fetal aneuploidy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25449088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23553438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "endSection": "title" }, { "offsetInBeginSection": 420, "offsetInEndSection": 956, "text": "In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24352524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25238658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044397", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23553438", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23553438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23553438", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Motivations for undertaking DNA sequencing-based non-invasive prenatal testing for fetal aneuploidy: a qualitative study with early adopter patients in Hong Kong.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24312358", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "OBJECTIVE: To determine whether non-invasive prenatal testing by maternal plasma DNA sequencing can uncover all fetal chromosome aneuploidies in one simple sequencing event. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23299662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22500971", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25238658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "endSection": "abstract" }, { "offsetInBeginSection": 28, "offsetInEndSection": 227, "text": "non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": " Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 564, "text": "The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies. Because false-positive results may occur, an abnormal result must be validated by invasive prenatal testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "endSection": "abstract" }, { "offsetInBeginSection": 3503, "offsetInEndSection": 3811, "text": "When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy. (II-2A) If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749753", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 958, "text": "Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044397", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23553438", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "[Cell-free nucleic acid-based non-invasive prenatal diagnosis of fetal aneuploidies].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23089167", "endSection": "title" }, { "offsetInBeginSection": 3931, "offsetInEndSection": 4149, "text": "Maternal age alone is a poor minimum standard for prenatal screening for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603453", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Non-invasive prenatal testing (NIPT) by massively parallel sequencing is a useful clinical test for the detection of common fetal aneuploidies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667696", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 455, "text": "The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "endSection": "abstract" } ] }, { "body": "Which packages are used for performing overlap analysis of genomic regions in R/bioconductor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23950696" ], "ideal_answer": [ "IRanges, GenomicRanges, and GenomicFeatures provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization.", "At the core of the infrastructure are three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization." ], "exact_answer": [ [ "IRanges" ], [ "GenomicRanges" ], [ "GenomicFeatures" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281" ], "type": "list", "id": "56a3bf0f496b62f23f00000a", "snippets": [ { "offsetInBeginSection": 193, "offsetInEndSection": 792, "text": "At the core of the infrastructure are three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23950696", "endSection": "abstract" } ] }, { "body": "Is dichlorphenamide effective for periodic paralysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3374500", "http://www.ncbi.nlm.nih.gov/pubmed/18345024", "http://www.ncbi.nlm.nih.gov/pubmed/6855804", "http://www.ncbi.nlm.nih.gov/pubmed/18426576", "http://www.ncbi.nlm.nih.gov/pubmed/10632100", "http://www.ncbi.nlm.nih.gov/pubmed/19019313", "http://www.ncbi.nlm.nih.gov/pubmed/18254068" ], "ideal_answer": [ "Yes, dichlorphenamide is effective for periodic paralysis. Dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4249177", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004005" ], "type": "yesno", "id": "56c1d841ef6e39474100002d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18345024", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1866, "text": "In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18254068", "endSection": "abstract" }, { "offsetInBeginSection": 2550, "offsetInEndSection": 2759, "text": "AUTHORS' CONCLUSIONS: The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18254068", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 812, "text": "For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19019313", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 858, "text": "Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18426576", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1373, "text": " In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10632100", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 418, "text": "Diclofenamid has now already been administered for 2 years. It is well tolerated and has suppressed further attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3374500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 428, "text": "Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive interattack muscle weakness, who became unresponsive or worsened by acetazolamide, responded favorably to dichlorophenamide, a more potent carbonic anhydrase inhibitor. Dichlorophenamide in single-blind placebo-controlled trials, considerably improved functional strength in two of the patients and had a moderate but definite effect in the third.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6855804", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1254, "text": "Dichlorophenamide should be considered as an alternate to acetazolamide in the treatment of patients with HOPP-associated interattack muscle weakness who have become unresponsive or worsened by acetazolamide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6855804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18345024", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1013, "text": "For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19019313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18345024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18345024", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 916, "text": "For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. A second trial, comparing dichlorphenamide with acetazolamide versus placebo, is currently in progress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19019313", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 812, "text": "Despite our better understanding of the pathogenesis of these disorders, current treatments are largely empirical and the evidence in favor of specific therapy largely anecdotal. For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19019313", "endSection": "abstract" } ] }, { "body": "What is evaluated with the Hydrocephalus Outcome Questionnaire?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18754895", "http://www.ncbi.nlm.nih.gov/pubmed/17644917", "http://www.ncbi.nlm.nih.gov/pubmed/21778677", "http://www.ncbi.nlm.nih.gov/pubmed/19714338", "http://www.ncbi.nlm.nih.gov/pubmed/16238072", "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "http://www.ncbi.nlm.nih.gov/pubmed/20593981", "http://www.ncbi.nlm.nih.gov/pubmed/21961548", "http://www.ncbi.nlm.nih.gov/pubmed/15835100", "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "http://www.ncbi.nlm.nih.gov/pubmed/16426953", "http://www.ncbi.nlm.nih.gov/pubmed/15835099" ], "ideal_answer": [ "The Hydrocephalus Outcome Questionnaire (HOQ) is a simple, reliable, and valid measure of health status in children with hydrocephalus." ], "type": "summary", "id": "56c1d84aef6e394741000030", "snippets": [ { "offsetInBeginSection": 166, "offsetInEndSection": 395, "text": "We sought to describe the natural history of this disorder, specifically its clinical presentation, disease course and long-term health status impact using the validated, disease-specific Hydrocephalus Outcome Questionnaire (HOQ)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21778677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "OBJECT: The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of measuring quality of life, but the cognitive component of this questionnaire has never been formally compared with gold-standard neuropsychological test scores. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21961548", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 591, "text": "Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 607, "text": "Measures of QOL were the Hydrocephalus Outcome Questionnaire and the Health Utilities Index Mark 3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19714338", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 604, "text": "METHODS: The families of children between 5 and 18 years of age with previously treated hydrocephalus at 3 Canadian pediatric neurosurgery centers completed measures of QOL: the Hydrocephalus Outcome Questionnaire (HOQ) and the Health Utilities Index Mark 3 (HUI3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20593981", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1285, "text": "In older children with hydrocephalus, the cHOQ appears to be a scientifically reliable means of assessing long-term outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18754895", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1424, "text": "The HOQ is a simple and very useful measurement for determining outcome in pediatric hydrocephalus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644917", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 322, "text": "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "OBJECTIVE: To compare three separate methods for establishing interpretability for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426953", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 1287, "text": "These include general outcome measures such as the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children, which measure physical function and independence in chronically ill and disabled children as well as disease-specific measures for hydrocephalus (Hydrocephalus Outcome Questionnaire), cerebral palsy (gross motor function and performance measures), head injury (Pediatric Cerebral Performance Category and Children's Coma Scale), and oncology (Pediatric Cancer Quality-of-Life Inventory).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16238072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "An instrument to measure the health status in children with hydrocephalus: the Hydrocephalus Outcome Questionnaire.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "title" }, { "offsetInBeginSection": 198, "offsetInEndSection": 410, "text": " The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1959, "text": "CONCLUSIONS: The HOQ for children with hydrocephalus demonstrated excellent reliability and validity properties. This tool will be valuable for a wide range of clinical research projects in pediatric hydrocephalus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "OBJECT: In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835100", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 526, "text": "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835100", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 612, "text": "The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of measuring quality of life, but the cognitive component of this questionnaire has never been formally compared with gold-standard neuropsychological test scores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21961548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "To compare three separate methods for establishing interpretability for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426953", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 411, "text": "The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "OBJECTIVE: To compare three separate methods for establishing interpretability for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426953", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 323, "text": "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "OBJECT: In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835100", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 402, "text": "The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1396, "text": "The HOQ is a simple and very useful measurement for determining outcome in pediatric hydrocephalus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644917", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 1298, "text": "These include general outcome measures such as the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children, which measure physical function and independence in chronically ill and disabled children as well as disease-specific measures for hydrocephalus (Hydrocephalus Outcome Questionnaire), cerebral palsy (gross motor function and performance measures), head injury (Pediatric Cerebral Performance Category and Children's Coma Scale), and oncology (Pediatric Cancer Quality-of-Life Inventory).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16238072", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 741, "text": "Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing. Clinical variables including number of shunt revisions, shunt infection and surgical decompression of foramen magnum, which may influence outcome, were investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 575, "text": " Adult patients under routine follow-up were assessed in a joint neurosurgery/neuropsychology clinic. Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 320, "text": "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of measuring quality of life, but the cognitive component of this questionnaire has never been formally compared with gold-standard neuropsychological test scores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21961548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Outcome in pediatric hydrocephalus: a comparison between previously used outcome measures and the hydrocephalus outcome questionnaire.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644917", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 575, "text": "Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835100", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 590, "text": "Measures of QOL were the Hydrocephalus Outcome Questionnaire and the Health Utilities Index Mark 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19714338", "endSection": "abstract" } ] }, { "body": "What is known about maternal smoking and brain tumor risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7139628", "http://www.ncbi.nlm.nih.gov/pubmed/15191928", "http://www.ncbi.nlm.nih.gov/pubmed/24260161", "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "http://www.ncbi.nlm.nih.gov/pubmed/12115571", "http://www.ncbi.nlm.nih.gov/pubmed/8850274", "http://www.ncbi.nlm.nih.gov/pubmed/11452935", "http://www.ncbi.nlm.nih.gov/pubmed/10620527" ], "ideal_answer": [ "Findings regarding association of maternal smoking and brain tumor risk are mixed. It was shown that children of women who smoked during pregnancy had an increased incidence of brain tumors (hazard ratio = 1.24; 95% confidence interval: 1.01-1.53). The increase in risk was similar for benign and malignant tumors, and was most apparent for astrocytoma. However, other authors did not find association between maternal smoking and brain tumor risk." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:368", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012907", "http://www.disease-ontology.org/api/metadata/DOID:1319", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009035" ], "type": "summary", "id": "56c1d85fef6e394741000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "BACKGROUND: A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260161", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "OBJECTIVE: Studies of the effect of maternal smoking during pregnancy on development of brain tumors in the offspring generally have found no increase in risk but most have mainly relied on retrospective exposure assessment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 1092, "text": "Children of women who smoked during pregnancy had an increased incidence of brain tumors (hazard ratio = 1.24; 95% confidence interval: 1.01-1.53). The increase in risk was similar for benign and malignant tumors, and was most apparent for astrocytoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1321, "text": "CONCLUSIONS: These results support a role for maternal smoking during pregnancy in the etiology of childhood brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1360, "text": "Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15191928", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1185, "text": "There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12115571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Maternal smoking during pregnancy and the risk of childhood brain tumors: a meta-analysis of 6566 subjects from twelve epidemiological studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "OBJECTIVE: Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract" }, { "offsetInBeginSection": 1485, "offsetInEndSection": 1707, "text": "Pooling all twelve reports yielded an RRs of 1.05 (0.90-1.21), a non-statistically significant result suggesting no clear association between maternal smoking during pregnancy and risk of childhood brain tumor development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract" }, { "offsetInBeginSection": 1911, "offsetInEndSection": 2075, "text": ".CONCLUSION: The available epidemiological data do not support a clear association between maternal smoking during pregnancy and pediatric brain tumor development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 1024, "text": "We observed only few positive associations, namely, between CNS tumors and low birth weight [<2,500 g; odds ratio (OR), 1.73; 95% confidence interval (CI), 1.06-2.84], between ependymoma and maternal smoking during pregnancy (>10 cigarettes per day: OR, 4.71; 95% CI, 1.69-13.1), and between astrocytoma and exposure to wood preservatives (OR, 1.91; 95% CI, 1.22-3.01). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11452935", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1068, "text": "The results on exposure to paternal tobacco smoke suggest an association with brain tumors (RR 1.22; CI, 1.05-1. 40; based on 10 studies) and lymphomas (RR 2.08; CI, 1.08-3.98; 4 studies). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10620527", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1588, "text": "No association was found between the risk of CBTs and maternal or paternal smoking before pregnancy and there was no association between CBTs and maternal smoking during pregnancy [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.72-1.3]. A slightly increased OR for CBTs was found for paternal smoking during pregnancy in the absence of maternal smoking (OR = 1.2; 95% CI = 0.90-1.5) and for maternal exposure to passive smoke from any source (OR = 1.2; 95% CI = 0.95-1.6). The results of this analysis are consistent with results from several prior epidemiological studies that showed no significant association between CBTs and maternal smoking before or during pregnancy or maternal exposure to passive smoke during pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8850274", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 1295, "text": "No significant differences in risks were found to be associated with maternal or paternal smoking at any time (odds ratio (OR) = 0.92 for mothers and 1.06 for fathers), during the year of birth of the child (which included both the prenatal and postnatal periods) (ORs = 0.84 for<1 pack/day and 1.0 for>or = 1 pack/day for mothers, and 0.68 for<1 pack/day and 1.07 for>or = 1 pack/day for fathers), or 2 years before the child was born, i.e., the pre-conception period (ORs = 0.75 for<1 pack/day and 1.01 for>or = 1 pack/day for mothers, and 0.90 for<1 pack/day and 1.15 for>or = 1 pack/day for fathers). Mothers were also specifically asked if they smoked during the pregnancy, and no association was found compared with never smokers (OR = 1.08, 95% confidence interval (CI) 0.80-1.45) or for ever-smokers who continued to smoke during pregnancy compared with those who stopped smoking during pregnancy (OR = 1.15, 95% CI 0.75-1.78). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "endSection": "abstract" }, { "offsetInBeginSection": 1489, "offsetInEndSection": 1775, "text": "The lack of an effect of parental smoking was observed for both the major histologic types and locations of brain tumors. These findings and those from earlier studies provide no support for the hypothesis that parental cigarette smoking influences the risk of brain tumors in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 758, "text": "Increased risk was associated with maternal contact with nitrosamine-containing substances such as burning incense (odds ratio, 3.3; p = 0.005), sidestream cigarette smoke (odds ratio, 1.5; p = 0.03), and face makeup (odds ratio, 1.6; p = 0.02); with maternal use of diuretics (odds ratio, 2.0; p = 0.03) and antihistamines (odds ratio, 3.4; p = 0.002); and with the level of maternal consumption of cured meats (p = 0.008).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7139628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Studies of the effect of maternal smoking during pregnancy on development of brain tumors in the offspring generally have found no increase in risk but most have mainly relied on retrospective exposure assessment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1338, "text": "No association was found between the risk of CBTs and maternal or paternal smoking before pregnancy and there was no association between CBTs and maternal smoking during pregnancy [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.72-1.3].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8850274", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1451, "text": "There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12115571", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1270, "text": "RESULTS: We found positive interaction odds ratios (ORs) for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P(interaction)\u200a=\u200a0.02; 0.10), such that children with the high-risk (greater PAH activation) genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260161", "endSection": "abstract" }, { "offsetInBeginSection": 1311, "offsetInEndSection": 1504, "text": "Finally, no significant increase in risk of brain tumors was found for the child's passive exposure to parental smoking during the period from birth to diagnosis of the brain tumor in the case.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1691, "text": "a non-statistically significant result suggesting no clear association between maternal smoking during pregnancy and risk of childhood brain tumor development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1286, "text": "These results support a role for maternal smoking during pregnancy in the etiology of childhood brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract" } ] }, { "body": "Which pathway is activated by ficolin-3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21890891", "http://www.ncbi.nlm.nih.gov/pubmed/18006063", "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "http://www.ncbi.nlm.nih.gov/pubmed/19535802", "http://www.ncbi.nlm.nih.gov/pubmed/23142462", "http://www.ncbi.nlm.nih.gov/pubmed/24336142", "http://www.ncbi.nlm.nih.gov/pubmed/19939495", "http://www.ncbi.nlm.nih.gov/pubmed/18261799", "http://www.ncbi.nlm.nih.gov/pubmed/25178935" ], "ideal_answer": [ "Ficolin-3 activates lectin complement pathway." ], "exact_answer": [ "lectin complement pathway" ], "concepts": [ "http://www.uniprot.org/uniprot/FCN3_HUMAN" ], "type": "factoid", "id": "56c1d856ef6e394741000032", "snippets": [ { "offsetInBeginSection": 93, "offsetInEndSection": 231, "text": "This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Ficolin-3 (also called H-ficolin or Hakata antigen) is a complement-activating pattern recognition molecule, possessing a fibrinogen-like domain involved in carbohydrate binding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25178935", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 625, "text": "Lectin pathway activity via Ficolin-3 was measured in ELISA on acetylated bovine serum albumin (acBSA) and measured as Ficolin-3 binding and deposition of C4, C3 and the terminal complement complex (TCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1686, "text": "Furthermore, Ficolin-3 mediated complement activation may be valuable in monitoring disease activity in SLE patients due to the high sensitivity for complement consumption in the assay independent of the Ficolin-3 concentration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVES: To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336142", "endSection": "abstract" }, { "offsetInBeginSection": 1303, "offsetInEndSection": 1649, "text": "CONCLUSION: Our data provide evidence that LCP is activated after SAH and that the actual plasma concentrations of ficolin-3 reflect the severity of brain injury as evaluated by clinical and structural parameters. These results support the idea that ficolin-3-mediated functional LCP activity may be targeted to control injury progression in SAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336142", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "MBL-associated serine protease-3 circulates in high serum concentrations predominantly in complex with Ficolin-3 and regulates Ficolin-3 mediated complement activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19939495", "endSection": "title" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1303, "text": "Moreover, Ficolin-3 has a high complement activating potential and is the only collagenase proteolytic resistant molecule among the lectin complement pathway initiators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006063", "endSection": "abstract" }, { "offsetInBeginSection": 1592, "offsetInEndSection": 1794, "text": "Moreover, Ficolin-3 is the primary acceptor molecule of MASP-3 among the LCP activator molecules, but MASP-3 appears to down-regulate Ficolin-3 mediated complement activation through the lectin pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19939495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Ficolin-3 (Hakata antigen or H-ficolin) is a soluble pattern recognition molecule in the lectin complement pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18261799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Ficolin-3, encoded by the FCN3 gene and expressed in the lung and liver, is a recognition molecule in the lectin pathway of the complement system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19535802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Ficolin-1, -2 and -3 are recognition molecules in the lectin complement pathway and form complexes with serine proteases named MASP-1, -2 and -3 and two nonenzymatic proteins. MASP-2 is the main initiator of lectin pathway activation, while ficolin-3 is the most abundant ficolin molecule in the circulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23142462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Ficolin-3 (also called H-ficolin or Hakata antigen) is a complement-activating pattern recognition molecule, possessing a fibrinogen-like domain involved in carbohydrate binding. Amongst human ficolins, Ficolin-3 has the highest concentration in serum and is the most potent lectin pathway activator in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25178935", "endSection": "abstract" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1756, "text": "Moreover, Ficolin-3 is the primary acceptor molecule of MASP-3 among the LCP activator molecules, but MASP-3 appears to down-regulate Ficolin-3 mediated complement activation through the lectin pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19939495", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 781, "text": "Moreover, these LPS/ficolin-3 complexes activated the lectin pathway of complement in a C4b-deposition assay in a calcium- and magnesium-dependent way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21890891", "endSection": "abstract" } ] }, { "body": "Is nivolumab used for treatment of Non\u2013Small-Cell Lung Cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "http://www.ncbi.nlm.nih.gov/pubmed/25965365", "http://www.ncbi.nlm.nih.gov/pubmed/24685885", "http://www.ncbi.nlm.nih.gov/pubmed/25704439", "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "http://www.ncbi.nlm.nih.gov/pubmed/24402925", "http://www.ncbi.nlm.nih.gov/pubmed/25496336" ], "ideal_answer": [ "Yes, nivolumab used for treatment of Non\u2013Small-Cell Lung Cancer." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002289", "http://www.disease-ontology.org/api/metadata/DOID:3908" ], "type": "yesno", "id": "56bb68a5ac7ad1001900000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 428, "text": "BACKGROUND: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "endSection": "abstract" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1855, "text": "CONCLUSIONS: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 741, "text": "Agents currently in active clinical development for lung cancer include ipilimumab, which modulates the cytotoxic T-lymphocyte-associated antigen 4 pathway, and multiple agents targeting the programmed death protein 1 (PD-1) pathway, both anti-PD-1 compounds (nivolumab, pembrolizumab [MK-3475]) and those that target programmed death ligand 1 (PD-L1), a key ligand for PD-1 (BMS-936559, MPDL3280A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "endSection": "title" }, { "offsetInBeginSection": 318, "offsetInEndSection": 666, "text": "We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial.PATIENTS AND METHODS: Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1752, "text": "CONCLUSION: Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Two PD-1 inhibitors, Bristol-Myers Squibb's nivolumab and Merck's MK-3475, both demonstrated positive results in phase I trials of previously treated patients with non-small cell lung cancer, reported at the World Conference on Lung Cancer in Sydney, Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24402925", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 923, "text": "Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25496336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Two PD-1 inhibitors, Bristol-Myers Squibb's nivolumab and Merck's MK-3475, both demonstrated positive results in phase I trials of previously treated patients with non-small cell lung cancer, reported at the World Conference on Lung Cancer in Sydney, Australia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24402925", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 936, "text": "Nivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25965365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25704439", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": " Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25704439", "endSection": "abstract" }, { "offsetInBeginSection": 1708, "offsetInEndSection": 2011, "text": " Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25704439", "endSection": "abstract" } ] }, { "body": "Global quantitative phosphoproteomic analyses are emerging. List the preferred technologies for the enrichment for phosphorylated peptides?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22345495", "http://www.ncbi.nlm.nih.gov/pubmed/20340162", "http://www.ncbi.nlm.nih.gov/pubmed/23485197", "http://www.ncbi.nlm.nih.gov/pubmed/20927383", "http://www.ncbi.nlm.nih.gov/pubmed/22499768", "http://www.ncbi.nlm.nih.gov/pubmed/21822884", "http://www.ncbi.nlm.nih.gov/pubmed/22499769", "http://www.ncbi.nlm.nih.gov/pubmed/22369663", "http://www.ncbi.nlm.nih.gov/pubmed/22906719", "http://www.ncbi.nlm.nih.gov/pubmed/17372656" ], "triples": [ { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0031684", "o": "http://linkedlifedata.com/resource/umls/label/A0319731" } ], "ideal_answer": [ "There are many different approaches to enrich for phosphorylated peptides: titanium dioxide, IMAC, simple derivatization through phosphoramidate chemistry and antibodies." ], "exact_answer": [ [ "enriched for phosphorylated peptides using titanium dioxide" ], [ "sequential elution from IMAC" ], [ "simple derivatization procedure based on phosphoramidate chemistry" ], [ "antiphosphotyrosine antibodies" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010748", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045163", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "list", "id": "516281e6298dcd4e51000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "TiSH--a robust and sensitive global phosphoproteomics strategy employing a combination of TiO2, SIMAC, and HILIC.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906719", "endSection": "title" }, { "offsetInBeginSection": 429, "offsetInEndSection": 740, "text": "An initial TiO(2) phosphopeptide pre-enrichment step is followed by post-fractionation using sequential elution from IMAC (SIMAC) to separate multi- and mono-phosphorylated peptides, and hydrophilic interaction liquid chromatography (HILIC) of the mono-phosphorylated peptides (collectively abbreviated \"TiSH\").", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906719", "endSection": "sections.0" }, { "offsetInBeginSection": 618, "offsetInEndSection": 729, "text": "After enrichment by anti-phosphotyrosine antibodies, we identified 29 potential novel c-Src substrate proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22499769", "endSection": "sections.0" }, { "offsetInBeginSection": 579, "offsetInEndSection": 845, "text": "Combining immunoprecipitation with an antiphosphotyrosine antibody, titanium dioxide phosphopeptide enrichment, isobaric tag for the relative and absolute quantitation methodology, and strong cation exchange separation, we were able to identify 2814 phosphopeptides.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22499768", "endSection": "sections.0" }, { "offsetInBeginSection": 443, "offsetInEndSection": 710, "text": "Phosphopeptide fractionation by strong cation exchange chromatography combined with immobilized metal affinity chromatography (IMAC) enrichment enabled quantification of more than 8000 distinct phosphorylation sites in Ppt1 wild-type versus Ppt1-deficient yeast cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22369663", "endSection": "sections.0" }, { "offsetInBeginSection": 710, "offsetInEndSection": 868, "text": "By employing titanium dioxide in addition to antiphosphotyrosine antibodies as enrichment methods, we identified 4164 phosphopeptides on 1670 phosphoproteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345495", "endSection": "sections.0" }, { "offsetInBeginSection": 676, "offsetInEndSection": 942, "text": "Our method combines the use of strong cation exchange (SCX) and titanium dioxide (TiO(2)) for phosphopeptide enrichment, high-resolution MS for peptide and protein identification, and stable isotope labeling by amino acids in cell culture (SILAC) for quantification.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21822884", "endSection": "sections.0" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1136, "text": "Phosphopeptides were isolated with high specificity through a simple derivatization procedure based on phosphoramidate chemistry.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17372656", "endSection": "sections.0" } ] }, { "body": "Which histone modifications are correlated with transcription elongation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21347206", "http://www.ncbi.nlm.nih.gov/pubmed/19365074", "http://www.ncbi.nlm.nih.gov/pubmed/20139424", "http://www.ncbi.nlm.nih.gov/pubmed/23401853", "http://www.ncbi.nlm.nih.gov/pubmed/22876190", "http://www.ncbi.nlm.nih.gov/pubmed/24722509", "http://www.ncbi.nlm.nih.gov/pubmed/24600005" ], "ideal_answer": [ "This is accompanied by reductions in the level of H3K36 trimethylation, a posttranslational histone modification associated with efficient transcriptional elongation, and the number of full-length transcripts from these genes. The 3' ZNF exons contain H3K36me3, a mark of transcriptional elongation." ], "exact_answer": [ [ "H3K36me3" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016570", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421" ], "type": "list", "id": "56c3326750c68dd41600000b", "snippets": [ { "offsetInBeginSection": 857, "offsetInEndSection": 1084, "text": " This is accompanied by reductions in the level of H3K36 trimethylation, a posttranslational histone modification associated with efficient transcriptional elongation, and the number of full-length transcripts from these genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24600005", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1352, "text": "Also like BUR kinase and the PAF complex, the Spt5 CTR is important for histone H2B K123 monoubiquitination and histone H3 K4 and K36 trimethylation during transcription elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19365074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B ubiquitylation to regulate transcript elongation in fission yeas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22876190", "endSection": "title" }, { "offsetInBeginSection": 249, "offsetInEndSection": 419, "text": " Mono-ubiquitylation of histone H2B (H2Bub1) plays a key role in coordinating co-transcriptional histone modification by promoting site-specific methylation of histone H3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22876190", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 583, "text": "We further characterized the histone modifications at the 3' ZNF exons and found that these regions also contain H3K36me3, a mark of transcriptional elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21347206", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 1152, "text": "To test the hypothesis that the contradictory modifications are due to imprinting, we used a SNP analysis of RNA-seq data to demonstrate that both alleles of certain ZNF genes having H3K9me3 and H3K36me3 are transcribed. We next analyzed isolated ZNF 3' exons using stably integrated episomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21347206", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Set2-mediated H3 Lys(36) methylation is a histone modification that has been demonstrated to function in transcriptional elongation by recruiting the Rpd3S histone deacetylase complex to repress intragenic cryptic transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20139424", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1689, "text": "Overall, our results show and suggest that multiple H4, H2A, and H3 residues contribute to and form a Set2 docking/recognition site on the nucleosomal surface so that proper Set2-mediated H3 Lys(36) di- and trimethylation, histone acetylation, and transcriptional elongation can occur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20139424", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 872, "text": "Sp3 depletion correlated with increased H3K36me3 and H2Bub1, two histone modifications associated with transcription elongation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401853", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 868, "text": "Using a SIR-regulated heat shock-inducible transgene, hsp82-2001, and a natural drug-inducible subtelomeric gene, YFR057w, as models we demonstrate that substantial transcriptional induction (>200-fold) can occur in the context of restricted histone loss and negligible levels of H3K4 trimethylation, H3K36 trimethylation and H3K79 dimethylation, modifications commonly linked to transcription initiation and elongation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24722509", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 874, "text": "Sp3 depletion correlated with increased H3K36me3 and H2Bub1, two histone modifications associated with transcription elongation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401853", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 874, "text": "Sp3 depletion correlated with increased H3K36me3 and H2Bub1, two histone modifications associated with transcription elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401853", "endSection": "abstract" } ] }, { "body": "Does thyroid hormone receptor beta1 affect insulin secretion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17293442" ], "ideal_answer": [ "No" ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/INS_APLCA", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.uniprot.org/uniprot/THB_MOUSE", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ], "type": "yesno", "id": "516c0e08298dcd4e5100006d", "snippets": [ { "offsetInBeginSection": 282, "offsetInEndSection": 434, "text": "We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17293442", "endSection": "sections.0" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1014, "text": "The silencing of TRbeta1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17293442", "endSection": "sections.0" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1385, "text": "T3 is able to specifically activate Akt in the islet beta cells rRINm5F and hCM through the interaction between TRbeta1 and PI3K p85alpha, demonstrating the involvement of TRbeta1 in this novel T3 non-genomic action in islet beta cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17293442", "endSection": "sections.0" } ] }, { "body": "List disorders that have been associated to the polymorphism rs2535629.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22472876", "http://www.ncbi.nlm.nih.gov/pubmed/25461954", "http://www.ncbi.nlm.nih.gov/pubmed/24373612" ], "ideal_answer": [ "schizophrenia and major depressive disorder. " ], "exact_answer": [ [ "schizophrenia" ], [ "major depressive disorder" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110" ], "type": "list", "id": "54d646403706e89528000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24373612", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 336, "text": "he aim of the study was to replicate the association of rs2535629 with schizophrenia and major depressive disorder (MDD) in Japanese subjects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24373612", "endSection": "abstract" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1323, "text": "In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 \u00d7 10(-8)), and all were in a 248\u2009kb interval of high LD on 3p21.1 (chr3:52\u2009425\u2009083-53\u2009822\u2009102, minimum P=5.9 \u00d7 10(-9) at rs2535629).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22472876", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 790, "text": "However, there was no preferential transmission at the ITIH3 rs52535629 polymorphism (\u03c7\u00b2=0.14, P=0.707).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25461954", "endSection": "abstract" } ] }, { "body": "What is targeted by monoclonal antibody Pembrolizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25891173", "http://www.ncbi.nlm.nih.gov/pubmed/25324906", "http://www.ncbi.nlm.nih.gov/pubmed/24685885", "http://www.ncbi.nlm.nih.gov/pubmed/25605845", "http://www.ncbi.nlm.nih.gov/pubmed/25034862", "http://www.ncbi.nlm.nih.gov/pubmed/25828465", "http://www.ncbi.nlm.nih.gov/pubmed/25960664", "http://www.ncbi.nlm.nih.gov/pubmed/26028255" ], "ideal_answer": [ "Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. Pembrolizumab is approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways." ], "exact_answer": [ "programmed cell death 1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000911" ], "type": "factoid", "id": "56c1f01aef6e394741000043", "snippets": [ { "offsetInBeginSection": 343, "offsetInEndSection": 742, "text": "gents currently in active clinical development for lung cancer include ipilimumab, which modulates the cytotoxic T-lymphocyte-associated antigen 4 pathway, and multiple agents targeting the programmed death protein 1 (PD-1) pathway, both anti-PD-1 compounds (nivolumab, pembrolizumab [MK-3475]) and those that target programmed death ligand 1 (PD-L1), a key ligand for PD-1 (BMS-936559, MPDL3280A). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685885", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 503, "text": "Ipilimumab (CTLA-4) and pembrolizumab (PD-1) are approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25605845", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 264, "text": "Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25891173", "endSection": "abstract" }, { "offsetInBeginSection": 1740, "offsetInEndSection": 1936, "text": "CONCLUSIONS: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25891173", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 483, "text": "METHODS: We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26028255", "endSection": "abstract" }, { "offsetInBeginSection": 2170, "offsetInEndSection": 2306, "text": "CONCLUSIONS: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26028255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828465", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 564, "text": "We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828465", "endSection": "abstract" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1219, "text": "Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody and pembrolizumab, a monoclonal antibody targeting programmed death 1 receptor may be a feasible treatment option in patients with metastatic mucosal melanoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25324906", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 692, "text": "Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25960664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25034862", "endSection": "title" }, { "offsetInBeginSection": 1525, "offsetInEndSection": 1936, "text": "Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%).CONCLUSIONS: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25891173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 777, "text": "BACKGROUND: The anti-programmed-death-receptor-1 (PD-1) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma. We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma.METHODS: In an open-label, international, multicentre expansion cohort of a phase 1 trial, patients (aged ?18 years) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were randomly assigned with a computer-generated allocation schedule (1:1 final ratio) to intravenous pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks until disease progression, intolerable toxicity, or consent withdrawal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25034862", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1221, "text": "Vemurafenib and dabrafenib are targeted agents for patients with BRAF mutation-positive melanoma. Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody and pembrolizumab, a monoclonal antibody targeting programmed death 1 receptor may be a feasible treatment option in patients with metastatic mucosal melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25324906", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 840, "text": "Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25960664", "endSection": "abstract" } ] }, { "body": "Does replication timing affect the rate of somatic mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23327985", "http://www.ncbi.nlm.nih.gov/pubmed/23422670", "http://www.ncbi.nlm.nih.gov/pubmed/22023572", "http://www.ncbi.nlm.nih.gov/pubmed/23271586", "http://www.ncbi.nlm.nih.gov/pubmed/12941181", "http://www.ncbi.nlm.nih.gov/pubmed/9560368", "http://www.ncbi.nlm.nih.gov/pubmed/19287383", "http://www.ncbi.nlm.nih.gov/pubmed/23821616", "http://www.ncbi.nlm.nih.gov/pubmed/22114361", "http://www.ncbi.nlm.nih.gov/pubmed/22046001", "http://www.ncbi.nlm.nih.gov/pubmed/24598232", "http://www.ncbi.nlm.nih.gov/pubmed/21666225" ], "ideal_answer": [ "Mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome. In yeast the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence. In humans DNA replication patterns help shape the mutational landscapes of normal and cancer genomes.", "Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. The mutations were distributed randomly throughout the genome, independent of replication timing. Here, we show that the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Interestingly, 5% of the single base pair substitutions might represent double-slippage events that occurred at the junction of immediately adjacent repeats, resulting in a shift in the repeat boundary.", "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome" ], "exact_answer": "yes", "type": "yesno", "id": "5710dd61cf1c32585100002e", "snippets": [ { "offsetInBeginSection": 139, "offsetInEndSection": 324, "text": "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19287383", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 451, "text": "ll classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19287383", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 602, "text": "We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21666225", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 264, "text": "Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023572", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 459, "text": "DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "The mutational profile of the yeast genome is shaped by replication", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22114361", "endSection": "title" }, { "offsetInBeginSection": 211, "offsetInEndSection": 340, "text": "the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22114361", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 919, "text": "Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22114361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Late-replicating domains have higher divergence and diversity in Drosophila melanogaster", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22046001", "endSection": "title" }, { "offsetInBeginSection": 286, "offsetInEndSection": 382, "text": "Recent evidence also suggests that late replication is associated with high mutability in yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22046001", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 677, "text": "Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22046001", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 981, "text": "The mutation rate for DNA mismatch repair null strains was approximately 1 mutation per genome per generation, 225-fold greater than the wild-type rate. The mutations were distributed randomly throughout the genome, independent of replication timing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821616", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 218, "text": "Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 330, "text": "Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 603, "text": "Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 930, "text": "we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422670", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1439, "text": "In addition, certain chromosome rearrangements found in cancer cells and in cells exposed to ionizing radiation display a significant delay in replication timing of >3 hours that affects the entire chromosome(2,3). Recent work from our lab indicates that disruption of discrete cis-acting autosomal loci result in an extremely late replicating phenotype that affects the entire chromosome(4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23271586", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 510, "text": "A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12941181", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 972, "text": "Drake calculates that lytic RNA viruses display spontaneous mutation rates of approximately one per genome while most have mutation rates that are approximately 0.1 per genome (Drake 1993). This constancy of germline mutation rates among microbial species need not necessarily mean constancy of the somatic mutation rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9560368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23327985", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 510, "text": "Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12941181", "endSection": "abstract" }, { "offsetInBeginSection": 2048, "offsetInEndSection": 2229, "text": "In addition, this method allows for the unambiguous identification of chromosomal rearrangements that correlate with changes in replication timing that affect the entire chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23271586", "endSection": "abstract" } ] }, { "body": "Which metazaon species or taxa are known to lack selenoproteins", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18698431", "http://www.ncbi.nlm.nih.gov/pubmed/19744324", "http://www.ncbi.nlm.nih.gov/pubmed/22943432", "http://www.ncbi.nlm.nih.gov/pubmed/16260744", "http://www.ncbi.nlm.nih.gov/pubmed/19487332", "http://www.ncbi.nlm.nih.gov/pubmed/14710190" ], "ideal_answer": [ "Some insect genomes have lost the capacity of synthesizing selenoproteins. Several insect species without selenoproteins have been identified." ], "type": "summary", "id": "5172f8118ed59a060a000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Relaxation of selective constraints causes independent selenoprotein extinction in insect genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18698431", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 438, "text": "Selenoproteins are a diverse family of proteins notable for the presence of the 21st amino acid, selenocysteine. Until very recently, all metazoan genomes investigated encoded selenoproteins, and these proteins had therefore been believed to be essential for animal life. Challenging this assumption, recent comparative analyses of insect genomes have revealed that some insect genomes appear to have lost selenoprotein genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18698431", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 1377, "text": " In this paper we investigate in detail the fate of selenoproteins, and that of selenoprotein factors, in all available arthropod genomes. We use a variety of in silico comparative genomics approaches to look for known selenoprotein genes and factors involved in selenoprotein biosynthesis. We have found that five insect species have completely lost the ability to encode selenoproteins and that selenoprotein loss in these species, although so far confined to the Endopterygota infraclass, cannot be attributed to a single evolutionary event, but rather to multiple, independent events. Loss of selenoproteins and selenoprotein factors is usually coupled to the deletion of the entire no-longer functional genomic region, rather than to sequence degradation and consequent pseudogenisation. Such dynamics of gene extinction are consistent with the high rate of genome rearrangements observed in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18698431", "endSection": "abstract" }, { "offsetInBeginSection": 1718, "offsetInEndSection": 2084, "text": "Selenoproteins have been independently lost in several insect species, possibly as a consequence of the relaxation in insects of the selective constraints acting across metazoans to maintain selenoproteins. The dispensability of selenoproteins in insects may be related to the fundamental differences in antioxidant defense between these animals and other metazoans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18698431", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of Facioscapulohumeral muscular\ndystrophy (FSHD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22551571" ], "ideal_answer": [ "The mode of inheritance of Facioscapulohumeral muscular dystrophy is autosomal dominant." ], "exact_answer": [ "autosomal dominant" ], "concepts": [ "http://www.uniprot.org/uniprot/FRG2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:11727", "http://www.uniprot.org/uniprot/FRG2C_HUMAN", "http://www.uniprot.org/uniprot/FRG2B_HUMAN", "http://www.uniprot.org/uniprot/FRG1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020391", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009136", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009135", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.disease-ontology.org/api/metadata/DOID:9884", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918", "http://www.uniprot.org/uniprot/FRG1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:0050557" ], "type": "factoid", "id": "52e8e93498d023950500001e", "snippets": [ { "offsetInBeginSection": 94, "offsetInEndSection": 132, "text": "autosomal dominant mode of inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22551571", "endSection": "abstract" } ] }, { "body": "Is NOD1 activated in inflammation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23740944", "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "http://www.ncbi.nlm.nih.gov/pubmed/24829218", "http://www.ncbi.nlm.nih.gov/pubmed/24828250", "http://www.ncbi.nlm.nih.gov/pubmed/12813035", "http://www.ncbi.nlm.nih.gov/pubmed/18574154", "http://www.ncbi.nlm.nih.gov/pubmed/24279792", "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "http://www.ncbi.nlm.nih.gov/pubmed/23712977", "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "http://www.ncbi.nlm.nih.gov/pubmed/21715553", "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "http://www.ncbi.nlm.nih.gov/pubmed/24534531", "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "http://www.ncbi.nlm.nih.gov/pubmed/25253572", "http://www.ncbi.nlm.nih.gov/pubmed/25732381", "http://www.ncbi.nlm.nih.gov/pubmed/21677137", "http://www.ncbi.nlm.nih.gov/pubmed/21469090", "http://www.ncbi.nlm.nih.gov/pubmed/23162548", "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "http://www.ncbi.nlm.nih.gov/pubmed/23848281", "http://www.ncbi.nlm.nih.gov/pubmed/23259058" ], "ideal_answer": [ "Nod proteins fight off bacterial infections by stimulating proinflammatory signaling and cytokine networks and by inducing antimicrobial effectors, such as nitric oxide and antimicrobial peptides. NOD1 engagement generates an inflammatory response via activation of NF\u03baB and MAPK pathways and several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents. Together, Nod1 and Nod2 represent central players in the control of immune responses to bacterial infections and inflammation. Mice deficient for both Nod1 and Nod2 had attenuated inflammatory pathology, reduced levels of inflammatory cytokines, and increased colonization of the mucosal tissue", "Nod1/2 DKO mice show increased susceptibility for intestinal permeability while vascular permeability was not affected. The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions. The increased intestinal permeability is associated with enhanced inflammatory cytokine production and epithelial cell proliferation in Nod1-deficient mice as compared with wild-type mice. However, the influence of Rip2 was strictly dependent on infection conditions that favored expression of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (TTSS), as Rip2 was dispensable for inflammation when mice were infected with bacteria grown under conditions that promoted expression of the SPI-1 TTSS.", "Nod1 and Nod2 control bacterial infections and inflammation" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007249", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053474" ], "type": "yesno", "id": "57091eefcf1c325851000016", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 73, "text": "Nod1 and Nod2 control bacterial infections and inflammation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "title" }, { "offsetInBeginSection": 246, "offsetInEndSection": 370, "text": "The Nod proteins Nod1 and Nod2 are two NLR family members that trigger immune defense in response to bacterial peptidoglycan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 568, "text": "Nod proteins fight off bacterial infections by stimulating proinflammatory signaling and cytokine networks and by inducing antimicrobial effectors, such as nitric oxide and antimicrobial peptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 680, "text": "Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1035, "text": "Together, Nod1 and Nod2 represent central players in the control of immune responses to bacterial infections and inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "title" }, { "offsetInBeginSection": 677, "offsetInEndSection": 1093, "text": "we show that Nod1 deficiency results in the increased development of both colitis-associated and Apc tumor suppressor-related colon tumors. In the absence of Nod1 signaling, there is a greater disruption of the intestinal epithelial cell barrier due to chemically induced injury as manifested by increased surface epithelial apoptosis early on during chemically induced colitis and increased intestinal permeability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1282, "text": "The increased intestinal permeability is associated with enhanced inflammatory cytokine production and epithelial cell proliferation in Nod1-deficient mice as compared with wild-type mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1560, "text": "Depletion of the gut microbiota suppressed tumor development in Nod1-deficient mice, thus highlighting a link between the commensal bacteria within the intestine and the host innate immune Nod1 signaling pathway in the regulation inflammation-mediated colon cancer development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1079, "text": " NOD1 protein is expressed in the eye and promotes ocular inflammation in a dose- and time-dependent fashion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "NOD1 expression in the eye and functional contribution to IL-1beta-dependent ocular inflammation in mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 283, "text": "Polymorphisms in NOD1 are associated with autoinflammatory diseases characterized by uveitis such as Crohn's disease and sarcoidosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 457, "text": "NOD1 is homologous to NOD2, which is responsible for an autosomal dominant form of uveitis. Nonetheless, the role of NOD1 in intraocular inflammation has not been explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "endSection": "title" }, { "offsetInBeginSection": 291, "offsetInEndSection": 458, "text": "mice deficient for both Nod1 and Nod2 had attenuated inflammatory pathology, reduced levels of inflammatory cytokines, and increased colonization of the mucosal tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1400, "text": "The present study has demonstrated an unexpected role of Nod1 in the development of site-specific vascular inflammation, especially coronary arteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Nod1 ligands induce site-specific vascular inflammation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "title" }, { "offsetInBeginSection": 147, "offsetInEndSection": 270, "text": "The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 510, "text": "Several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "abstract" }, { "offsetInBeginSection": 1696, "offsetInEndSection": 1835, "text": "Systematic analysis of Nod1/2 DKO mice revealed a possible role of Nod1/2 in the development of renal disease during systemic inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "NOD1 and NOD2 Signaling in Infection and Inflammation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23162548", "endSection": "title" }, { "offsetInBeginSection": 303, "offsetInEndSection": 396, "text": "NOD1 engagement generates an inflammatory response via activation of NF\u03baB and MAPK pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1246, "text": "In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "endSection": "abstract" }, { "offsetInBeginSection": 1428, "offsetInEndSection": 1612, "text": "This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "NOD1 expression elicited by iE-DAP in first trimester human trophoblast cells and its potential role in infection-associated inflammation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "endSection": "title" }, { "offsetInBeginSection": 267, "offsetInEndSection": 462, "text": "This study aimed to investigate the expression and function of NOD1 in first trimester trophoblast cells, and evaluate the potential role of trophoblast cells in infection-associated inflammation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "endSection": "abstract" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1686, "text": "NOD1 may have a role in mediating infection-associated inflammation. Once iE-DAP is recognized by NOD1, the inflammatory response may be induced via NOD1-RICK-NF-\u03baB-mediated pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1252, "text": "NOD1/2(-/-) mice were protected from HFD-induced inflammation, lipid accumulation, and peripheral insulin intolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715553", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1007, "text": "In contrast, Nod1 gene-deficient mice developed enhanced joint inflammation with concomitant elevated levels of proinflammatory cytokines and cartilage damage, consistent with a model in which Nod1 controls the inflammatory reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18574154", "endSection": "abstract" }, { "offsetInBeginSection": 1565, "offsetInEndSection": 1794, "text": "These data indicate that the NLR family members Nod1 and Nod2 have different functions in controlling inflammation, and that intracellular Nod1-Nod2 interactions may determine the severity of arthritis in this experimental model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18574154", "endSection": "abstract" }, { "offsetInBeginSection": 1059, "offsetInEndSection": 1315, "text": "Whereas the lymphotoxin pathway was critical for the induction of the B cell chemoattractant CXCL13 in response to Nod1 agonists, B cell accumulation within the spleen following Nod1-induced systemic inflammation was independent of the lymphotoxin pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24534531", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 735, "text": "The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24829218", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 525, "text": "Nonetheless, the role of NOD1 in intraocular inflammation has not been explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "endSection": "title" }, { "offsetInBeginSection": 388, "offsetInEndSection": 522, "text": "We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21677137", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1166, "text": "In addition, recent studies have revealed a role for intracellular NOD1 receptors in the regulation of vascular inflammation and metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23848281", "endSection": "abstract" }, { "offsetInBeginSection": 1919, "offsetInEndSection": 2083, "text": "In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24829218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21677137", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 400, "text": "The nucleotide-binding oligomerisation domain (NOD) intracellular molecules recognise a wide range of microbial products, as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor \u03baB (NF\u03baB). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24829218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Nod1 ligands induce site-specific vascular inflammation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "endSection": "title" }, { "offsetInBeginSection": 169, "offsetInEndSection": 484, "text": "The nucleotide oligomerization domain (NOD) intracellular molecules recognize a wide range of microbial products as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor KB (NFKB), a central regulator of the terminal processes of human labor and delivery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23740944", "endSection": "abstract" }, { "offsetInBeginSection": 1865, "offsetInEndSection": 2003, "text": "CONCLUSIONS: We identify NOD proteins as innate immune components that are involved in diet-induced inflammation and insulin intolerance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "endSection": "title" }, { "offsetInBeginSection": 142, "offsetInEndSection": 308, "text": "In particular, muramyl peptides trigger inflammation, contribute to host defense against microbial infections, and modulate the adaptive immune response to antigens. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21469090", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 919, "text": "Systemic and tissue-specific inflammation was assessed using enzyme-linked immunosorbent assays in NOD ligand-injected mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715553", "endSection": "abstract" }, { "offsetInBeginSection": 1865, "offsetInEndSection": 2223, "text": "CONCLUSIONS: We identify NOD proteins as innate immune components that are involved in diet-induced inflammation and insulin intolerance. Acute activation of NOD proteins by mimetics of bacterial PGNs causes whole-body insulin resistance, bolstering the concept that innate immune responses to distinctive bacterial cues directly lead to insulin resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715553", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1043, "text": "Interferon-gamma (IFN gamma), which is a potent pro-inflammatory cytokine in intestinal mucosal inflammation, activates CARD4/NOD1 mRNA transcription in a time- and dose-dependent manner and results in augmentation of CARD4/NOD1 protein in SW480 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12813035", "endSection": "abstract" }, { "offsetInBeginSection": 1631, "offsetInEndSection": 1812, "text": "These studies suggest that the Th1 cytokine, IFN gamma, activates CARD4/NOD1 transcription and regulate innate immune mechanisms in the condition of intestinal mucosal inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12813035", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 202, "text": "NOD1 activation triggers inflammation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25253572", "endSection": "abstract" }, { "offsetInBeginSection": 1671, "offsetInEndSection": 1950, "text": "In contrast to enhanced leptin mRNA by LPS and TNF\u03b1, NOD1 activation suppressed leptin mRNA in adipocytes, suggesting the differential effects of NOD1 activation in adipocytes. Overall, our results suggest that NOD1 represents a novel target for adipose inflammation in obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23712977", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 290, "text": "NOD1 activation triggers inflammation, antimicrobial mechanisms and autophagy in both epithelial cells and murine macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25253572", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 519, "text": "NOD1 is an intracellular immune receptor that senses peptidoglycan from Gram-negative bacteria and responds by inducing autophagy and activating NF-\u03baB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering peptidoglycan structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25732381", "endSection": "abstract" }, { "offsetInBeginSection": 1438, "offsetInEndSection": 1635, "text": "Bacterial NOD1 activation is positioned as a component of metabolic endotoxemia that can contribute to hyperlipidemia, systemic inflammation and insulin resistance by acting directly on adipocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24828250", "endSection": "abstract" }, { "offsetInBeginSection": 1693, "offsetInEndSection": 1818, "text": "NOD1 ligand also caused inflammation and insulin resistance directly in primary hepatocytes from WT, but not NOD1(-/-), mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715553", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1621, "text": "We conclude that NOD1 activation reduced AHR in allergen-induced lung inflammation, which was accompanied by a reduction of allergen-specific T-cell proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24279792", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 631, "text": "The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24829218", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1044, "text": "Interferon-gamma (IFN gamma), which is a potent pro-inflammatory cytokine in intestinal mucosal inflammation, activates CARD4/NOD1 mRNA transcription in a time- and dose-dependent manner and results in augmentation of CARD4/NOD1 protein in SW480 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12813035", "endSection": "abstract" } ] }, { "body": "List diseases where protein citrullination plays an important role.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23701010", "http://www.ncbi.nlm.nih.gov/pubmed/20590842", "http://www.ncbi.nlm.nih.gov/pubmed/22505457", "http://www.ncbi.nlm.nih.gov/pubmed/20013286", "http://www.ncbi.nlm.nih.gov/pubmed/24081567", "http://www.ncbi.nlm.nih.gov/pubmed/23960723", "http://www.ncbi.nlm.nih.gov/pubmed/24298040", "http://www.ncbi.nlm.nih.gov/pubmed/17168521", "http://www.ncbi.nlm.nih.gov/pubmed/22560840", "http://www.ncbi.nlm.nih.gov/pubmed/20399192", "http://www.ncbi.nlm.nih.gov/pubmed/19830834", "http://www.ncbi.nlm.nih.gov/pubmed/18787103", "http://www.ncbi.nlm.nih.gov/pubmed/23856045", "http://www.ncbi.nlm.nih.gov/pubmed/18576335", "http://www.ncbi.nlm.nih.gov/pubmed/23828821", "http://www.ncbi.nlm.nih.gov/pubmed/23030787", "http://www.ncbi.nlm.nih.gov/pubmed/15704193", "http://www.ncbi.nlm.nih.gov/pubmed/23022892", "http://www.ncbi.nlm.nih.gov/pubmed/21136610", "http://www.ncbi.nlm.nih.gov/pubmed/23118341", "http://www.ncbi.nlm.nih.gov/pubmed/23576281", "http://www.ncbi.nlm.nih.gov/pubmed/16856138", "http://www.ncbi.nlm.nih.gov/pubmed/16730216" ], "ideal_answer": [ "Rheumatoid arthritis, multiple sclerosis, prion diseases, cancer and Alzheimer's disease are examples of diseases where protein citrullination involvement has been demonstrated." ], "exact_answer": [ [ "Multiple Sclerosis" ], [ "Alzheimer disease" ], [ "Rheumatoid Arthritis", "RA" ], [ "Prion Diseases" ], [ "Cancer" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0018101", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070613", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.biosemantics.org/jochem#4275497", "http://www.biosemantics.org/jochem#4275495", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016485", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006417", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002956" ], "type": "list", "id": "534df8c9aeec6fbd07000016", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 276, "text": "his modification has been linked to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22560840", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 477, "text": "Over the past decade, PADs and protein citrullination have been commonly implicated as abnormal pathological features in neurodegeneration and inflammatory responses associated with diseases such as multiple sclerosis, Alzheimer disease and rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022892", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1575, "text": "These findings suggest that PAD2 and citrullinated proteins may play a key role in the brain pathology of prion diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022892", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 397, "text": "We first discovered that abnormal myelin hypercitrullination, even in normal-appearing white matter, by peptidylarginine deiminases (PADs) correlates strongly with disease severity and might have an important role in MS progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118341", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1336, "text": " recent advances have shown that the once obscure modification known as citrullination is involved in the onset and progression of inflammatory diseases and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576281", "endSection": "abstract" }, { "offsetInBeginSection": 1637, "offsetInEndSection": 1766, "text": "These observations may reflect a role of P. gingivalis in the protein citrullination, which is related to the pathogenesis of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23701010", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 200, "text": "Protein citrullination has been detected in the CNS and associated with a number of neurological diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23828821", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 572, "text": "Protein and peptide citrullination are important in the development of rheumatoid arthritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23856045", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 473, "text": "citrullination has been shown to be associated with several diseases, such as cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298040", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1389, "text": " Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505457", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 646, "text": "citrullinated protein also has a negative side, because this protein's accumulation in the brain is a possible cause of Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20590842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The aim of the present work was to study the effect of tobacco smoking on disease progression in rheumatoid arthritis patients and its relation to anti-cyclical citrullinated peptide (anti-CCP) antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23960723", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1385, "text": "It appears from our results that, tobacco smoking mostly play a role in progression of rheumatoid arthritis through tissue protein citrullination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23960723", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 458, "text": "we have reported pathological characterization of PAD2 and citrullinated proteins in scrapie-infected mice, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20013286", "endSection": "abstract" }, { "offsetInBeginSection": 1338, "offsetInEndSection": 1495, "text": "aberrant citrullinated proteins could play a role in pathogenesis and have value as a marker for the postmortem classification of neurodegenerative diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20013286", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 695, "text": "We previously reported that abnormal protein citrullination by PAD2 has been closely associated with the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and prion disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830834", "endSection": "abstract" }, { "offsetInBeginSection": 1511, "offsetInEndSection": 1697, "text": "This study suggests that accumulated citrullinated proteins and abnormal activation of PAD2 may function in the pathogenesis of prion diseases and serve as potential therapeutic targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18787103", "endSection": "abstract" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1339, "text": "PTMs such as citrullination due to alterations of peptidylarginine deiminase activity or generation of RA-specific epitopes, should be considered as a trigger in tolerance break.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21136610", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 146, "text": "Protein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA)-specific autoantibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18576335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Protein citrullination, a once-obscure post-translational modification (PTM) of peptidylarginine, has recently become an area of significant interest because of its suspected role in human disease states, including rheumatoid arthritis and multiple sclerosis, and also because of its newfound role in gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17168521", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 579, "text": "he increased levels of citrullinated CNS proteins associated with MS are also observed during the development of EAE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16856138", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 708, "text": "Rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease are examples of human diseases where protein citrullination involvement has been demonstrated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16730216", "endSection": "abstract" }, { "offsetInBeginSection": 1993, "offsetInEndSection": 2080, "text": "citrullinated proteins may become a useful marker for human neurodegenerative diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15704193", "endSection": "abstract" } ] }, { "body": "What is commotio cordis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21699851", "http://www.ncbi.nlm.nih.gov/pubmed/14646469", "http://www.ncbi.nlm.nih.gov/pubmed/11048776", "http://www.ncbi.nlm.nih.gov/pubmed/11208236", "http://www.ncbi.nlm.nih.gov/pubmed/11334832", "http://www.ncbi.nlm.nih.gov/pubmed/17957272", "http://www.ncbi.nlm.nih.gov/pubmed/22869311", "http://www.ncbi.nlm.nih.gov/pubmed/22816548", "http://www.ncbi.nlm.nih.gov/pubmed/17229310", "http://www.ncbi.nlm.nih.gov/pubmed/23107651", "http://www.ncbi.nlm.nih.gov/pubmed/15331287", "http://www.ncbi.nlm.nih.gov/pubmed/10392228", "http://www.ncbi.nlm.nih.gov/pubmed/9930916", "http://www.ncbi.nlm.nih.gov/pubmed/10894918", "http://www.ncbi.nlm.nih.gov/pubmed/22027166", "http://www.ncbi.nlm.nih.gov/pubmed/15744544", "http://www.ncbi.nlm.nih.gov/pubmed/6496438", "http://www.ncbi.nlm.nih.gov/pubmed/9703576", "http://www.ncbi.nlm.nih.gov/pubmed/20086611", "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "http://www.ncbi.nlm.nih.gov/pubmed/18691236", "http://www.ncbi.nlm.nih.gov/pubmed/10338239", "http://www.ncbi.nlm.nih.gov/pubmed/11555799", "http://www.ncbi.nlm.nih.gov/pubmed/10498299", "http://www.ncbi.nlm.nih.gov/pubmed/19749607" ], "ideal_answer": [ "Commotio cordis is a term used to describe cases of blunt thoracic impact causing sudden death without structural damage of the heart" ], "exact_answer": [ "blunt thoracic impact causing sudden death" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056104" ], "type": "factoid", "id": "53035d7c2059c6d71c000085", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Commotio cordis is a rare type of blunt cardiac injury in which low impact chest trauma causes sudden cardiac arrest, usually occurs from being struck by a projectile during sports.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22816548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "Commotio cordis due to blunt trauma to the precordium is a rare cause of death in young athletes, occurring less frequently than all of the other athletics-related deaths. Commotio cordis is a term used to describe cases of blunt thoracic impact causing fatality without structural damage of the heart and internal organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14646469", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 223, "text": "Although blunt, nonpenetrating chest blows causing sudden cardiac death (commotio cordis) are often associated with competitive sports, dangers implicit in such blows can extend into many other life activities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Sudden death following blunt chest trauma is a frightening occurrence known as 'commotio cordis' or 'concussion of the heart'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10894918", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 169, "text": "Commotio cordis is a term used to describe cases of blunt thoracic impact causing fatality without gross structural damage of the heart and internal organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10498299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Cardiac concussion, previously known as commotio cordis, occurs in structurally normal hearts without gross or microscopic injury to the myocardium, cardiac valves, or coronary arteries, as opposed to other sports-related deaths known to occur more frequently in structural or congenital heart disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9703576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Nonpenetrating cardiac injuries due to direct precordial blunt impacts are a commonly encountered phenomenon in medicolegal offices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6496438", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 472, "text": "less commonly occurring manifestation of nonpenetrating injury is a concussion of the heart (commotio cordis), often with dramatic physiological consequences but no morphologic cardiac injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6496438", "endSection": "abstract" } ] }, { "body": "What is the cause of Phthiriasis Palpebrarum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26451147", "http://www.ncbi.nlm.nih.gov/pubmed/24909484", "http://www.ncbi.nlm.nih.gov/pubmed/16903509", "http://www.ncbi.nlm.nih.gov/pubmed/12523816", "http://www.ncbi.nlm.nih.gov/pubmed/20339456", "http://www.ncbi.nlm.nih.gov/pubmed/19728949", "http://www.ncbi.nlm.nih.gov/pubmed/24556565", "http://www.ncbi.nlm.nih.gov/pubmed/22707338", "http://www.ncbi.nlm.nih.gov/pubmed/23993722", "http://www.ncbi.nlm.nih.gov/pubmed/12898406", "http://www.ncbi.nlm.nih.gov/pubmed/24157356" ], "ideal_answer": [ "Phthiriasis palpebrarum is a rare eyelid infestation caused by phthirus pubis." ], "exact_answer": [ "Pthirus pubis" ], "type": "factoid", "id": "56bb68f9ac7ad1001900000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes. We report a case of unilateral phthiriasis palpebrarum with crab louse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26451147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "BACKGROUND: Pediculosis capitis is a common parasitic infestation, whereas phthiriasis palpebrarum is an uncommon infection due to Phthirus pubis (pubic lice) inoculating the eyelashes and surrounding tissues of the eye. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24556565", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1212, "text": "Head lice typically do not infect the eyes, and given the different morphology of the lice on the patient's head and eyes, a diagnosis of phthiriasis palpebrarum was made. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24556565", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 613, "text": "P. pubis can cause pruritic eyelid margins or unusual blepharoconjunctivitis. We present a case of phthiriasis palpebrarum in a 4-year-old boy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23993722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "INTRODUCTION: Phthiriasis palpebrarum is an ectoparasitosis in which Phthirus pubis infest the eyelashes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157356", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1206, "text": "In all cases, the diagnosis of phthiriasis palpebrarum was confirmed by parasitological examination of eyelashes, which revealed the presence of adult and nit forms of Phthirus pubis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157356", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 720, "text": " Based on the observation of numerous nits at the base of the eyelashes and the ectoparasite in the palpebral margin, a diagnosis of phthiriasis palpebrarum was made.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Phthiriasis palpebrarum (lice infestation of palpabrae) is a rarely reported disorder and may present as blepharoconjuctivitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20339456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Phthiriasis palpebrarum, caused by Phthirus pubis, is an uncommon cause of blepharoconjunctivitis; therefore, this condition is easily misdiagnosed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12898406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16903509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26451147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Phthiriasis palpebrarum is an unusual cause of blepharoconjunctivitis and may easily be overlooked because of the failure of physicians to recognize Phthirus pubis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12523816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20339456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16903509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Phthiriasis palpebrarum is an infestation of the eyelashes caused by the louse Pthirus pubis (Linnaeus, 1758). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Phthiriasis palpebrarum, caused by Phthirus pubis, is an uncommon cause of blepharoconjunctivitis; therefore, this condition is easily misdiagnosed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12898406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16903509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes. We report a case of unilateral phthiriasis palpebrarum with crab louse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26451147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Phthiriasis palpebrarum is an infestation of the eyelashes caused by the louse Pthirus pubis (Linnaeus, 1758). We report a case of phthiriasis palpebrarum in a 6-year-old girl, which was initially misdiagnosed as allergic blepharoconjunctivitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Phthiriasis palpebrarum is an unusual cause of blepharoconjunctivitis and may easily be overlooked because of the failure of physicians to recognize Phthirus pubis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12523816", "endSection": "abstract" } ] }, { "body": "Does the histidine-rich Ca-binding protein (HRC) interact with triadin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12480542", "http://www.ncbi.nlm.nih.gov/pubmed/25451386", "http://www.ncbi.nlm.nih.gov/pubmed/17030629", "http://www.ncbi.nlm.nih.gov/pubmed/11504710", "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "http://www.ncbi.nlm.nih.gov/pubmed/19403607", "http://www.ncbi.nlm.nih.gov/pubmed/17526652", "http://www.ncbi.nlm.nih.gov/pubmed/22040806", "http://www.ncbi.nlm.nih.gov/pubmed/10531621", "http://www.ncbi.nlm.nih.gov/pubmed/11741309" ], "ideal_answer": [ "Yes. HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart. A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported.", "Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) and binds to triadin (TRN), a protein associated with the ryanodine receptor and thought to be involved in calcium release." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4263030", "http://www.uniprot.org/uniprot/TRDN_CANFA" ], "type": "yesno", "id": "54c12fd1f693c3b16b000001", "snippets": [ { "offsetInBeginSection": 528, "offsetInEndSection": 626, "text": "The HRC effects on RyR may be regulated by the Ca(2+)-sensitivity of its interaction with triadin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 286, "text": "In rabbit skeletal and cardiac muscles, HRC binds to sarcoplasmic reticulum (SR) membranes via triadin, a junctional SR protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22040806", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1684, "text": "HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526652", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 190, "text": "Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA affecting Ca(2+) cycling in the SR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 832, "text": "HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk between SR Ca(2+) uptake and release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19403607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "The histidine-rich Ca(2+) binding protein (HRC) is a high capacity Ca(2+) binding protein in the sarcoplasmic reticulum (SR). Because HRC appears to interact directly with triadin, HRC may play a role in the regulation of Ca(2+) release during excitation-contraction coupling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12480542", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 463, "text": "In the present study, we have performed co-immunoprecipitation experiments and show that HRC binds directly to triadin, which is an integral membrane protein of the sarcoplasmic reticulum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11504710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11741309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The present study documents the binding interaction of skeletal muscle sarcoplasmic reticulum (SR) transmembrane protein triadin with peripheral histidine-rich, Ca(2+)-binding protein (HCP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10531621", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1100, "text": "In addition, the intra-luminal histidine-rich calcium binding protein (HRC) has been shown to interact with both SERCA2a and triadin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451386", "endSection": "abstract" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1252, "text": "Notably, there is physical and direct interaction between these protein players, mediating a fine-cross talk between SR Ca-uptake, storage and release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451386", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 677, "text": "The histidine-rich calcium-binding protein (HRCBP) is expressed in the junctional SR, the site of calcium release from the SR. HRCBP is expressed exclusively in muscle tissues and binds calcium with low affinity and high capacity. In addition, HRCBP interacts with triadin, a protein associated with the ryanodine receptor and thought to be involved in calcium release. Its calcium binding properties, localization to the SR, and interaction with triadin suggest that HRCBP is involved in calcium handling by the SR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17030629", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 615, "text": "Using a fusion protein binding assay, we further identified the histidine-rich acidic repeats of HRC as responsible for the binding of HRC to triadin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11504710", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 1107, "text": "The HRC binding domain of triadin was also localized by fusion protein binding assay to the lumenal region containing the KEKE motif that was previously shown to be involved in the binding of triadin to calsequestrin. Notably, the interaction of HRC and triadin is Ca(2+)-sensitive. Our data suggest that HRC may play a role in the regulation of Ca(2+) release from the sarcoplasmic reticulum by interaction with triadin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11504710", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 556, "text": "Further support for colocalization of HRC with triadin cytoplasmic domain is provided here by experiments of mild tryptic digestion of tightly sealed TC vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11741309", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 888, "text": "We demonstrate that HRC can be isolated as a complex with triadin, following equilibrium sucrose-density centrifugation in the presence of mM Ca(2+).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11741309", "endSection": "abstract" }, { "offsetInBeginSection": 889, "offsetInEndSection": 1146, "text": "Here, we characterized the COOH-terminal portion of rabbit HRC, expressed and purified as a fusion protein (HRC(569-852)), with respect to Ca(2+)-binding properties, and to the interaction with triadin on blots, as a function of the concentration of Ca(2+).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11741309", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1472, "text": "Our results identify the polyglutamic stretch near the COOH terminus, as the Ca(2+)-binding site responsible, both for the acceleration in mobility of HRC on SDS-PAGE in the presence of millimolar concentrations of Ca(2+), and for the enhancement by high Ca(2+) of the interaction between HRC and triadin cytoplasmic segment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11741309", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 523, "text": "In addition to providing further evidence that HCP coenriches with RyR1, FKBP-12, triadin and calsequestrin (CS) in sucrose-density-purified TC vesicles, using specific polyclonal antibody, we show it to be expressed as a single protein species, both in fast-twitch and slow-twitch fibers, and to identically localize to the I-band.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10531621", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 773, "text": "Colocalization of HCP and triadin at junctional triads is supported by the overlapping staining pattern using monoclonal antibodies to triadin. We show a specific binding interaction between digoxigenin-HCP and triadin, using ligand blot techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10531621", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1143, "text": "Suggesting that triadin dually interacts with HCP and with CS, at distinct sites, we have found that triadin-CS interaction in overlays does not require the presence of Ca2+.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10531621", "endSection": "abstract" }, { "offsetInBeginSection": 1472, "offsetInEndSection": 1667, "text": "These differential effects form the basis for the hypothesis that HCP anchors to the junctional membrane domain of the SR, through binding to triadin short cytoplasmic domain at the NH2 terminus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10531621", "endSection": "abstract" }, { "offsetInBeginSection": 1668, "offsetInEndSection": 1906, "text": "Although the function of this interaction, as such, is not well understood, it seems of potential biological interest within the more general context of the structural-functional role of triadin at the triadic junction in skeletal muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10531621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "BACKGROUND: Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA affecting Ca(2+) cycling in the SR. Chronic overexpression of HRC that may disrupt intracellular Ca(2+) homeostasis is implicated in pathogenesis of cardiac hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Interaction of HRC (histidine-rich Ca(2+)-binding protein) and triadin in the lumen of sarcoplasmic reticulum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11504710", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 294, "text": "The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526652", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 292, "text": "The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526652", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 275, "text": "Because HRC appears to interact directly with triadin, HRC may play a role in the regulation of Ca(2+) release during excitation-contraction coupling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12480542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11741309", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 293, "text": "The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526652", "endSection": "abstract" } ] }, { "body": "How are CpG island shores defined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24057217", "http://www.ncbi.nlm.nih.gov/pubmed/19951682", "http://www.ncbi.nlm.nih.gov/pubmed/20944598", "http://www.ncbi.nlm.nih.gov/pubmed/19151715", "http://www.ncbi.nlm.nih.gov/pubmed/23887935", "http://www.ncbi.nlm.nih.gov/pubmed/19881528", "http://www.ncbi.nlm.nih.gov/pubmed/20720541", "http://www.ncbi.nlm.nih.gov/pubmed/23157493", "http://www.ncbi.nlm.nih.gov/pubmed/22479372" ], "ideal_answer": [ "CpG island \"shores\" are defined as genomic regions up to 2kb distant to known CpG islands. Differential DNA methylation correlates with gene expression more strongly at CpG island shores than CpG islands." ], "concepts": [ "http://www.uniprot.org/uniprot/MECP2_HUMAN", "http://www.uniprot.org/uniprot/MBD10_ARATH", "http://www.uniprot.org/uniprot/MBD12_ARATH", "http://www.uniprot.org/uniprot/MB3L1_HUMAN", "http://www.uniprot.org/uniprot/MBD4_HUMAN", "http://www.uniprot.org/uniprot/MBD1_MOUSE", "http://www.uniprot.org/uniprot/MECP2_RAT", "http://www.uniprot.org/uniprot/MB3L5_HUMAN", "http://www.uniprot.org/uniprot/MBD1_ARATH", "http://www.uniprot.org/uniprot/MB3L2_HUMAN", "http://www.uniprot.org/uniprot/MB3L4_HUMAN", "http://www.uniprot.org/uniprot/MBD3_MOUSE", "http://www.uniprot.org/uniprot/MBD9_ARATH", "http://www.uniprot.org/uniprot/MB3L3_HUMAN", "http://www.uniprot.org/uniprot/MB3L1_MOUSE", "http://www.uniprot.org/uniprot/MECP2_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008327", "http://www.uniprot.org/uniprot/CXXC1_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051718", "http://www.uniprot.org/uniprot/F8I2_HUMAN", "http://www.uniprot.org/uniprot/MBD5_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899", "http://www.uniprot.org/uniprot/MBD6_HUMAN", "http://www.uniprot.org/uniprot/HINFP_BOVIN", "http://www.uniprot.org/uniprot/F8I2_MOUSE", "http://www.uniprot.org/uniprot/MBD4_ARATH", "http://www.uniprot.org/uniprot/HINFP_HUMAN", "http://www.uniprot.org/uniprot/MBD1_HUMAN", "http://www.uniprot.org/uniprot/MBD3_HUMAN", "http://www.uniprot.org/uniprot/MBD2_HUMAN", "http://www.uniprot.org/uniprot/MBD6_ARATH", "http://www.uniprot.org/uniprot/MBD5_ARATH", "http://www.uniprot.org/uniprot/MBD11_ARATH", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051783", "http://www.uniprot.org/uniprot/CXXC1_BOVIN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044027", "http://www.uniprot.org/uniprot/MBD4_MOUSE", "http://www.uniprot.org/uniprot/MBD2_MOUSE", "http://www.uniprot.org/uniprot/MBD13_ARATH", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044029", "http://www.uniprot.org/uniprot/MBD6_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045322", "http://www.uniprot.org/uniprot/MBD5_HUMAN", "http://www.uniprot.org/uniprot/MBD7_ARATH", "http://www.uniprot.org/uniprot/MTSI_SPISQ", "http://www.uniprot.org/uniprot/MBD3_ARATH", "http://www.uniprot.org/uniprot/MBD8_ARATH", "http://www.uniprot.org/uniprot/MECP2_MACFA", "http://www.uniprot.org/uniprot/HINFP_MOUSE", "http://www.uniprot.org/uniprot/CXXC1_MOUSE", "http://www.uniprot.org/uniprot/MBD2_ARATH" ], "type": "summary", "id": "52d3cc5203868f1b06000037", "snippets": [ { "offsetInBeginSection": 362, "offsetInEndSection": 550, "text": "Here we show that most methylation alterations in colon cancer occur not in promoters, and also not in CpG islands, but in sequences up to 2 kb distant, which we term 'CpG island shores'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19151715", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 347, "text": " Here, we find substantial hypermethylation and hypomethylation of cytosine-phosphate-guanine (CpG) island shores in nine human iPS cell lines as compared to their parental fibroblasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19881528", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Recent genome-wide descriptions of CpG methylation patterns in mammalian cells identified many differentially methylated regions (DMRs) located at CpG island \"shores.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19951682", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1285, "text": "Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720541", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 521, "text": "This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22479372", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1222, "text": "We observed that methylation probes associated with expression in cis were more likely to be located outside CpG islands, whereas specificity for CpG island shores was present when methylation, associated with expression, was under local genetic control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23157493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Aberrant DNA methylation of CpG islands, CpG island shores and first exons is known to play a key role in the altered gene expression patterns in all human cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23887935", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1417, "text": "In particular, neuronal-type differential methylation was overrepresented in CpG island shores, enriched within gene bodies but not in intergenic regions, and preferentially harbored binding motifs for a distinct set of transcription factors, including neuron-specific activity-dependent factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24057217", "endSection": "abstract" } ] }, { "body": "Does magnesium sulfate improve outcomes of subarachnoid hemorrhage patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21299874", "http://www.ncbi.nlm.nih.gov/pubmed/19398856", "http://www.ncbi.nlm.nih.gov/pubmed/18705917", "http://www.ncbi.nlm.nih.gov/pubmed/21125466", "http://www.ncbi.nlm.nih.gov/pubmed/22170177", "http://www.ncbi.nlm.nih.gov/pubmed/16463831", "http://www.ncbi.nlm.nih.gov/pubmed/15790946", "http://www.ncbi.nlm.nih.gov/pubmed/19658274", "http://www.ncbi.nlm.nih.gov/pubmed/16759446", "http://www.ncbi.nlm.nih.gov/pubmed/16628069", "http://www.ncbi.nlm.nih.gov/pubmed/21748496", "http://www.ncbi.nlm.nih.gov/pubmed/23931043", "http://www.ncbi.nlm.nih.gov/pubmed/12632115", "http://www.ncbi.nlm.nih.gov/pubmed/16164489", "http://www.ncbi.nlm.nih.gov/pubmed/22633825", "http://www.ncbi.nlm.nih.gov/pubmed/24619389", "http://www.ncbi.nlm.nih.gov/pubmed/11883835", "http://www.ncbi.nlm.nih.gov/pubmed/22890635", "http://www.ncbi.nlm.nih.gov/pubmed/20538692", "http://www.ncbi.nlm.nih.gov/pubmed/17121134", "http://www.ncbi.nlm.nih.gov/pubmed/20228677", "http://www.ncbi.nlm.nih.gov/pubmed/19828484", "http://www.ncbi.nlm.nih.gov/pubmed/16159090", "http://www.ncbi.nlm.nih.gov/pubmed/23002400", "http://www.ncbi.nlm.nih.gov/pubmed/17536487", "http://www.ncbi.nlm.nih.gov/pubmed/19370322", "http://www.ncbi.nlm.nih.gov/pubmed/15753761", "http://www.ncbi.nlm.nih.gov/pubmed/21608279", "http://www.ncbi.nlm.nih.gov/pubmed/17636626", "http://www.ncbi.nlm.nih.gov/pubmed/19812935", "http://www.ncbi.nlm.nih.gov/pubmed/25201463", "http://www.ncbi.nlm.nih.gov/pubmed/16427437", "http://www.ncbi.nlm.nih.gov/pubmed/22966500", "http://www.ncbi.nlm.nih.gov/pubmed/20378868", "http://www.ncbi.nlm.nih.gov/pubmed/20334471", "http://www.ncbi.nlm.nih.gov/pubmed/18054611", "http://www.ncbi.nlm.nih.gov/pubmed/22059101", "http://www.ncbi.nlm.nih.gov/pubmed/11426093", "http://www.ncbi.nlm.nih.gov/pubmed/21489317", "http://www.ncbi.nlm.nih.gov/pubmed/19700328", "http://www.ncbi.nlm.nih.gov/pubmed/16463861", "http://www.ncbi.nlm.nih.gov/pubmed/16723884" ], "ideal_answer": [ "No. Although initial studies have provided with encouraging findings regarding administration of magnesium sulphate in aneurysmal subarachnoid haemorrhage patients, but subsequent larger studies have reported that intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended." ], "exact_answer": "no", "concepts": [ "http://www.biosemantics.org/jochem#4073442" ], "type": "yesno", "id": "54d62ede3706e89528000002", "snippets": [ { "offsetInBeginSection": 1687, "offsetInEndSection": 1937, "text": "CONCLUSION: Patients assigned a higher serum magnesium concentration had a reduced incidence of vasospasm as seen by angiography, but the difference was not statistically significant. Clinically significant outcomes were not different between groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23931043", "endSection": "abstract" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 2174, "text": "158 patients (26\u00b72%) had poor outcome in the magnesium group compared with 151 (25\u00b73%) in the placebo group (risk ratio [RR] 1\u00b703, 95% CI 0\u00b785-1\u00b725). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0\u00b796, 95% CI 0\u00b786-1\u00b708). INTERPRETATION: Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633825", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1177, "text": "There is a tendency in the magnesium group to have better outcomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22170177", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 865, "text": "Due to inconsistently reported benefits and the occurrence of side effects, phase II data suggested that intravenous magnesium for SAH provided either no overall net benefit or uncertain trade-offs. Benefit was likewise not supported in the single phase III clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21748496", "endSection": "abstract" }, { "offsetInBeginSection": 1923, "offsetInEndSection": 2262, "text": "tatistically significant clinical benefits could not be demonstrated for the other drugs (clazosentan, statins, and magnesium). CONCLUSIONS: Insufficient evidence is available to support the use of the triple-H therapy, clazosentan, statins, or magnesium sulfate for the prevention of cerebral vasospasm following subarachnoid hemorrhage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21608279", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 679, "text": "Magnesium sulfate decreased the rate of cerebral infarction, but not of DCI or poor functional outcome. Regarding outcome, a beneficial effect of magnesium sulfate on outcome can not be ruled out because of sample size limitations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21489317", "endSection": "abstract" }, { "offsetInBeginSection": 1497, "offsetInEndSection": 1901, "text": "CONCLUSIONS: The present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21299874", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1422, "text": "Favorable outcome (Good recovery and moderate disability, as defined by Glasgow Outcome Scale) was achieved in 20 of 30 (67%) patients receiving magnesium sulfate infusion and 16 of 30 (53%) patients receiving placebo treatment, p = 0.292, odds ratio 1.750, 95% CI 0.616-4.974.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21125466", "endSection": "abstract" }, { "offsetInBeginSection": 1739, "offsetInEndSection": 1851, "text": "Similarly, the pooled odds ratio for favorable outcome is 1.598, 95% CI 1.074-2.377, statistically significant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21125466", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 1156, "text": "RESULTS: The worst clinical outcomes at 6 months were seen in MgSO(4) group patients, with mean plasma magnesium concentrations in the fourth quartile, and in placebo group patients, with mean such concentrations in the third and fourth quartiles. CONCLUSIONS: No evidence was found to suggest that a higher mean plasma magnesium concentration improves clinical outcomes. On the contrary, we found an association between high plasma magnesium concentration and worse clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538692", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1388, "text": "The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378868", "endSection": "abstract" }, { "offsetInBeginSection": 1726, "offsetInEndSection": 1907, "text": "CONCLUSIONS: The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378868", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 952, "text": "Magnesium infusion reduced the risk of poor outcome and delayed cerebral ischemia (DCI): the relative risk was 0.62 (95% confidence interval (CI) 0.46-0.83) and 0.73 (95% CI 0.53-1.00), respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334471", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1290, "text": "CONCLUSION: The meta-analysis suggests that intravenous magnesium therapy reduces the risk of DCI and poor outcome after aneurysmal SAH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334471", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1575, "text": "The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20228677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND: A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812935", "endSection": "abstract" }, { "offsetInBeginSection": 1505, "offsetInEndSection": 1701, "text": "These data imply that intravenous magnesium therapy, besides a supposed beneficial effect on outcome, also provides pain relief for SAH patients, for whom it might also improve functional outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19828484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19658274", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 373, "text": "In a phase II randomized clinical trial of 283 patients, magnesium treatment reduced the risk of DCI by 34% and of poor outcome by 23%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "BACKGROUND: Recent studies suggest that high-dose MgSO4 therapy is safe and reduces the incidence of DIND and subsequent poor outcome after SAH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18054611", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1008, "text": "On-treatment analysis showed a significantly better outcome after 3 months (P = .017) and a trend toward better outcome after 1 year (P = .083). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18054611", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1455, "text": " CONCLUSIONS: High-dose MgSO4 therapy might be efficient as a prophylactic adjacent therapy after SAH to reduce the risk for poor outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18054611", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1652, "text": "There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4 treated group. CONCLUSIONS: Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17121134", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1144, "text": "There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16628069", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1204, "text": "Patients receiving MgSO4 tended to have fewer neurological deficits, better functional recovery and an improved score in GOS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16463861", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1532, "text": "CONCLUSIONS: MgSO4 infusion after aneurysmal SAH is well tolerated and may be useful in producing better outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16463861", "endSection": "abstract" }, { "offsetInBeginSection": 1488, "offsetInEndSection": 1642, "text": "CONCLUSION: Magnesium did not seem to interfere in vasospasm frequency but apparently acted favorably in decreasing morbidity and length of hospital stay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16427437", "endSection": "abstract" }, { "offsetInBeginSection": 1862, "offsetInEndSection": 2011, "text": "None of the patients died; no CT evidence of ischemic infarction was present; and most had good outcomes (GOS 5 in 10 patients; GOS 4 in 8 patients).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16159090", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1379, "text": "At that time, 18 patients in the treatment group and 6 in the placebo group had an excellent outcome (risk ratio, 3.4; 95% CI, 1.3 to 8.9). CONCLUSIONS: This study suggests that magnesium reduces DCI and subsequent poor outcome, but the results are not yet definitive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15790946", "endSection": "abstract" }, { "offsetInBeginSection": 2757, "offsetInEndSection": 2944, "text": "We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11883835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Magnesium sulfate treatment improves outcome in patients with subarachnoid hemorrhage: a meta-analysis study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23002400", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND AND PURPOSE: Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19658274", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1446, "text": "Our results indicate that although there was reduced likelihood of a poor outcome for patients treated with magnesium sulfate after SAH, patient mortality was not improved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19700328", "endSection": "abstract" }, { "offsetInBeginSection": 2183, "offsetInEndSection": 2405, "text": "CONCLUSION: Administration of intra-arterial magnesium sulfate in combination with nicardipine was well tolerated in patients with subarachnoid hemorrhage and cerebral vasospasm without a significant change in MAP and ICP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19370322", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1502, "text": "Current evidence does not support the prophylactic use of magnesium sulfate in aneurysmal subarachnoid hemorrhage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24619389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19658274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Despite the publication of several randomized controlled studies, there is still much debate on whether magnesium sulfate improves outcome in patients with aneurysmal subarachnoid hemorrhage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19700328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633825", "endSection": "abstract" } ] }, { "body": "Which gene is mutated in a subtype of arrhythmogenic right ventricular cardiomyopathy known as Naxos disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18937352", "http://www.ncbi.nlm.nih.gov/pubmed/21880664", "http://www.ncbi.nlm.nih.gov/pubmed/16096717", "http://www.ncbi.nlm.nih.gov/pubmed/21789513", "http://www.ncbi.nlm.nih.gov/pubmed/12574890", "http://www.ncbi.nlm.nih.gov/pubmed/11691526", "http://www.ncbi.nlm.nih.gov/pubmed/15851108", "http://www.ncbi.nlm.nih.gov/pubmed/10902626", "http://www.ncbi.nlm.nih.gov/pubmed/17924338", "http://www.ncbi.nlm.nih.gov/pubmed/22315228" ], "ideal_answer": [ "Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder associated with arrhythmias and sudden death. A recessive mutation in the gene encoding plakoglobin has been shown to cause Naxos disease, a cardiocutaneous syndrome characterized by ARVC and abnormalities of hair and skin.", "Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder associated with arrhythmias and sudden death. A recessive mutation in the gene encoding plakoglobin has been shown to cause Naxos disease, a cardiocutaneous syndrome characterized by ARVC and abnormalities of hair and skin. ", "A homozygous loss-of-function mutation of the Plakoglobin (Jup) gene, which encodes a major component of the desmosome and the adherens junction, had been identified in Naxos patients, although the underlying mechanism remained elusive.", "A homozygous loss-of-function mutation of the Plakoglobin (Jup) gene, had been identified in Naxos Disease patients, a subset of ARVC, which is characterized by cutaneous disorder." ], "exact_answer": [ "The Plakoglobin gene", "plakoglobin[jup]" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.disease-ontology.org/api/metadata/DOID:0050431" ], "type": "factoid", "id": "54f9ae2506d9727f76000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 517, "text": "Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritable myocardial disorder associated with fibrofatty replacement of myocardium and ventricular arrhythmia. A subset of ARVC is categorized as Naxos disease, which is characterized by ARVC and a cutaneous disorder. A homozygous loss-of-function mutation of the Plakoglobin (Jup) gene, which encodes a major component of the desmosome and the adherens junction, had been identified in Naxos patients, although the underlying mechanism remained elusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Loss-of-function mutation of Jup has been associated with Naxos disease, which is characterized by arrhythmogenic cardiomyopathy and the cutaneous disorder palmoplantar keratoderma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315228", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 337, "text": "Previously, we have shown that genetic ablation of Jup in cardiomyocytes in mice leads to arrhythmogenic cardiomyopathy similar to Naxos disease in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315228", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 520, "text": "As similar phenotypes have been described in Naxos disease and Carvajal syndrome, respectively, the genes for plakoglobin (JUP) and desmoplakin (DSP) were screened for mutations using direct genomic sequencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789513", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 554, "text": "One is a C-terminal mutation causing Naxos disease, a recessive syndrome of arrhythmogenic right ventricular cardiomyopathy (ARVC) and abnormal skin and hair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18937352", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 394, "text": "In this study, we examined the effects of two different mutations in plakoglobin on cell migration, stiffness, and adhesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18937352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder associated with arrhythmias and sudden death. A recessive mutation in the gene encoding plakoglobin has been shown to cause Naxos disease, a cardiocutaneous syndrome characterized by ARVC and abnormalities of hair and skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17924338", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1517, "text": "Three other genes implicated for ARVC, plakoglobin (Naxos disease), desmoplakin (ARVC8) and plakophilin (ARVC9) have prompted the speculation that ARVC is primarily a disease of desmosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16096717", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 271, "text": "We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851108", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 568, "text": "Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851108", "endSection": "abstract" }, { "offsetInBeginSection": 1463, "offsetInEndSection": 1736, "text": "However, in Naxos disease, a recessive form of ARVC with coexpression of palmoplantar keratoderma and woolly hair, a mutation in the plakoglobin gene has recently been discovered, thus underscoring the potential role of genetic alterations in cytoskeletal proteins in ARVC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12574890", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 490, "text": "Naxos disease is a recessively inherited ARVC caused by a mutation in the gene encoding plakoglobin (cell adhesion protein) in which the cardiac phenotype is associated with palmoplantar keratoderma and woolly hair. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11691526", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1734, "text": "Autosomal recessive ARVC caused by a mutation in plakoglobin was 100% penetrant by adolescence. Affected subjects who were homozygous experienced progressive disease with adverse prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11691526", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 546, "text": "Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an autosomal dominant heart muscle disorder that causes arrhythmia, heart failure, and sudden death. Previously we mapped the genetic locus for the triad of autosomal recessive ARVC, palmoplantar keratoderma, and woolly hair (Naxos disease) to chromosome 17q21, in which the gene for plakoglobin is encoded. This protein is a key component of desmosomes and adherens junctions, and is important for the tight adhesion of many cell types, including those in the heart and skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10902626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10902626", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851108", "endSection": "title" } ] }, { "body": "What is the role of edaravone in traumatic brain injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23564113", "http://www.ncbi.nlm.nih.gov/pubmed/23710445", "http://www.ncbi.nlm.nih.gov/pubmed/22977573", "http://www.ncbi.nlm.nih.gov/pubmed/17115943", "http://www.ncbi.nlm.nih.gov/pubmed/17115906", "http://www.ncbi.nlm.nih.gov/pubmed/24163818", "http://www.ncbi.nlm.nih.gov/pubmed/19590930", "http://www.ncbi.nlm.nih.gov/pubmed/24066191", "http://www.ncbi.nlm.nih.gov/pubmed/22982593", "http://www.ncbi.nlm.nih.gov/pubmed/22251821", "http://www.ncbi.nlm.nih.gov/pubmed/20398468", "http://www.ncbi.nlm.nih.gov/pubmed/21677777", "http://www.ncbi.nlm.nih.gov/pubmed/21732763", "http://www.ncbi.nlm.nih.gov/pubmed/19768539" ], "ideal_answer": [ "Edaravone, a free radical scavenger, has been shown to have neuroprotective effects after traumatic brain injury. In animal models, edaravone has been shown to reduce neuronal damage by scavenging reactive oxygen species (ROS), maintain intact the autoregulation of the cerebral vasculature, decrease neuronal loss, reduce programmed cell death, the presence of inflammatory cytokines, cerebral edema, and blood-brain barrier (BBB) permeability. Edaravone also protects against neurological deficits and memory deficits following traumatic brain injury." ], "concepts": [ "http://www.biosemantics.org/jochem#4278506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006259", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001930" ], "type": "summary", "id": "530e42bf5937551c09000005", "snippets": [ { "offsetInBeginSection": 1132, "offsetInEndSection": 1447, "text": " The edaravone-treated animals also exhibited higher rCBF in the contralateral hemisphere compared with that seen in -vehicle-treated animals. It is suggested that edaravone reduces neuronal damage by scavenging reactive oxygen species (ROS) and by maintaining intact the autoregulation of the cerebral vasculature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564113", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1309, "text": "Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease in O2 (\u2219-) levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23710445", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1092, "text": "Edaravone significantly suppressed axonal injury and oxidative stress in the cortex, corpus callosum, and hippocampus 24h after injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982593", "endSection": "abstract" }, { "offsetInBeginSection": 1577, "offsetInEndSection": 1741, "text": "These results suggest that edaravone protects against memory deficits following TBI and that this protection is mediated by suppression of TAI and oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982593", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 975, "text": "Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22977573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21732763", "endSection": "title" }, { "offsetInBeginSection": 657, "offsetInEndSection": 832, "text": "Edaravone treatment significantly decreased hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal programmed cell death compared to vehicle treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21732763", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1487, "text": "Lastly, edaravone treatment significantly reduced the presence of inflammatory cytokines, cerebral edema, blood-brain barrier (BBB) permeability, and, importantly, neurological deficits following TBI. Our results suggest that edaravone exerts a neuroprotective effect in the rat model of TBI. The likely mechanism is via inhibiting oxidative stress, leading to a decreased inflammatory response and glial activation, and thereby reducing neuronal death and improving neurological function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21732763", "endSection": "abstract" }, { "offsetInBeginSection": 1784, "offsetInEndSection": 2864, "text": "After treatment with edaravone, the degree of morphological injury, p-ERK1/2 level and number of apoptotic neurons decreased, latent period to find the safety platform was significantly shortened (in low-dose edaravone treatment group, p-ERK1/2 expression level at 6, 24, 48 hours was 2.46 + or - 0.22, 4.00 + or - 0.84, 2.38 + or - 0.32, and in high-dose edaravone treatment group was 1.67 + or - 0.15, 1.86 + or - 0.38, 1.27 + or - 0.28; in low-dose edaravone treatment group, the apoptotic cells at 6, 24, 48, 72 hours was 5.20 + or - 1.23, 7.10 + or - 1.72, 9.54 + or - 1.36, 14.12 + or - 3.19, and in high-dose edaravone treatment group was 3.40 + or - 0.49 , 4.39 + or - 0.73, 5.02 + or - 1.12, 8.78 + or - 2.16; in low-dose edaravone treatment group, latent period to find the safety platform at 7-10 days was 94.8 + or - 22.8, 65.2 + or - 19.0, 62.0 + or - 16.7, 59.5 + or - 15.6, and in high-dose edaravone treatment group it was 81.5 + or - 20.7, 55.4 + or - 18.5, 40.0 + or - 12.3, 32.2 + or - 11.0, all P<0.05). High-dose edaravone showed a better effect (all P<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20398468", "endSection": "abstract" }, { "offsetInBeginSection": 2876, "offsetInEndSection": 3057, "text": " Edaravone gives good therapeutic effect on severe TBI, and the molecular mechanism is related to attenuation of ERK1/2 pathway and neuronal apoptosis following severe brain trauma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20398468", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 1046, "text": "Numbers of 8-OHdG-, 4-HNE-, and ssDNA-positive cells around the damaged area after TBI were significantly decreased in the edaravone group compared with the saline group (P < 0.01). There was a significant increase in neuronal cell number and improvement in cerebral dysfunction after TBI in the edaravone group compared with the saline group (P < 0.01). Edaravone administration following TBI inhibited free radical-induced neuronal degeneration and apoptotic cell death around the damaged area. In summary, edaravone treatment improved cerebral dysfunction following TBI, suggesting its potential as an effective clinical therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19768539", "endSection": "abstract" }, { "offsetInBeginSection": 2284, "offsetInEndSection": 2562, "text": "Edaravone administration inhibited production of free radicals known to induce neuronal degeneration and cell death after brain injury, and protected nestin-positive cells, including NSCs, with the potential to differentiate into neurons and glia around the area damaged by TBI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19590930", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 419, "text": "Under specific experimental conditions, edaravone minimized traumatic brain injury by functioning as a synthetic antioxidant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17115943", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1564, "text": "Thus, edaravone can scavenge OR- and significantly reduce levels of these radicals in TBI patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17115906", "endSection": "abstract" } ] }, { "body": "Are there plasma membrane receptors for thyroid hormones?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11117200", "http://www.ncbi.nlm.nih.gov/pubmed/22986150", "http://www.ncbi.nlm.nih.gov/pubmed/20658515", "http://www.ncbi.nlm.nih.gov/pubmed/24113777", "http://www.ncbi.nlm.nih.gov/pubmed/6290538", "http://www.ncbi.nlm.nih.gov/pubmed/22945636", "http://www.ncbi.nlm.nih.gov/pubmed/169249", "http://www.ncbi.nlm.nih.gov/pubmed/18329679", "http://www.ncbi.nlm.nih.gov/pubmed/227209", "http://www.ncbi.nlm.nih.gov/pubmed/23137442", "http://www.ncbi.nlm.nih.gov/pubmed/23926648", "http://www.ncbi.nlm.nih.gov/pubmed/19900468", "http://www.ncbi.nlm.nih.gov/pubmed/22414628", "http://www.ncbi.nlm.nih.gov/pubmed/6093898", "http://www.ncbi.nlm.nih.gov/pubmed/17570630", "http://www.ncbi.nlm.nih.gov/pubmed/23021374", "http://www.ncbi.nlm.nih.gov/pubmed/20051527", "http://www.ncbi.nlm.nih.gov/pubmed/12165107", "http://www.ncbi.nlm.nih.gov/pubmed/17983645", "http://www.ncbi.nlm.nih.gov/pubmed/2534509", "http://www.ncbi.nlm.nih.gov/pubmed/23943159", "http://www.ncbi.nlm.nih.gov/pubmed/19755667", "http://www.ncbi.nlm.nih.gov/pubmed/8936679", "http://www.ncbi.nlm.nih.gov/pubmed/1747413", "http://www.ncbi.nlm.nih.gov/pubmed/6312037", "http://www.ncbi.nlm.nih.gov/pubmed/20232113" ], "ideal_answer": [ "Receptors for thyroid hormones are present on plasma membrane of cells; in particular thyroid hormones bind integrin that is a heterodimeric component of plasma membrane" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002462", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005886", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016020", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011989", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056921" ], "type": "yesno", "id": "532c169ed6d3ac6a3400001f", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 150, "text": "ntegrins are heterodimeric structural components of the plasma membrane whose ligands include a large number of extracellular matrix (ECM) proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23943159", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 660, "text": "Recently, integrin \u03b1v\u03b23 has been shown to have a panel of previously unappreciated small molecule receptor sites for thyroid hormone and hormone analogues, for dihydrotestosterone, and for resveratrol, a polyphenol that has certain estrogen-like features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23943159", "endSection": "abstract" }, { "offsetInBeginSection": 1541, "offsetInEndSection": 1666, "text": "The integrin receptor activation by T4 may take a role in plasma membrane processes involved in the male reproductive system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23137442", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 839, "text": "Rapid signaling via this plasma membrane binding site appears to be responsible for many nongenomic effects of thyroid hormones, independent of the classic nuclear receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22414628", "endSection": "abstract" } ] }, { "body": "Which disorder is rated by Palmini classification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25219355", "http://www.ncbi.nlm.nih.gov/pubmed/21275980", "http://www.ncbi.nlm.nih.gov/pubmed/23667118", "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "http://www.ncbi.nlm.nih.gov/pubmed/17535679", "http://www.ncbi.nlm.nih.gov/pubmed/22642611", "http://www.ncbi.nlm.nih.gov/pubmed/25296541", "http://www.ncbi.nlm.nih.gov/pubmed/23899121", "http://www.ncbi.nlm.nih.gov/pubmed/25601060", "http://www.ncbi.nlm.nih.gov/pubmed/20618424", "http://www.ncbi.nlm.nih.gov/pubmed/23551067", "http://www.ncbi.nlm.nih.gov/pubmed/22844307", "http://www.ncbi.nlm.nih.gov/pubmed/24649461", "http://www.ncbi.nlm.nih.gov/pubmed/15965699", "http://www.ncbi.nlm.nih.gov/pubmed/22510082" ], "ideal_answer": [ "Palmini classification system is used for classification of focal cortical dysplasia." ], "exact_answer": [ "focal cortical dysplasia" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002965" ], "type": "factoid", "id": "56c1f020ef6e394741000047", "snippets": [ { "offsetInBeginSection": 407, "offsetInEndSection": 584, "text": "This study also provides an opportunity to compare the predictive value of the ILAE and Palmini et al classification schemes with regard to the type I focal cortical dysplasias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1492, "text": "Of the 91 patients, there were 50 patients with ILAE focal cortical dysplasia type Ib, 41 with ILAE focal cortical dysplasia type Ic, 63 with Palmini et al focal cortical dysplasia type IA, and 28 with Palmini et al focal cortical dysplasia type IB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 2066, "text": "Crude analysis revealed no significant difference between patients with subtypes of ILAE focal cortical dysplasia type I or Palmini et al focal cortical dysplasia type I concerning postoperative outcome according to the Engel and ILAE scoring systems on seizure frequency. Our findings revealed no significant difference concerning surgical outcome with respect to seizure frequency for the histologic subtypes of ILAE focal cortical dysplasia type I (Ib vs Ic) or Palmini et al focal cortical dysplasia type I (IA vs IB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1100, "text": "MCD were classified following the existing classification schemes (Barkovich et al., 2012. Brain. 135, 1348-1369; Palmini et al., 2004. Neurology. 62, S2-S8) and the ILAE classification for FCD recently proposed by Bl\u00fcmcke in 2011. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25219355", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 1035, "text": "DISCUSSION: This short review provides an overview of the issues which account for the varied historical approaches to FCD classification and descriptions of gross pathologic findings associated with FCD and an overview of two more recently developed and widely used schema, the Palmini et al. (Neurology 62: S2-8, 2004) and the International League Against Epilepsy (ILAE) classifications Blumcke et al. Epilepsia 52: 158-174, 2011. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25296541", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 449, "text": " In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 761, "text": "Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23899121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Tuberous sclerosis complex (TSC) and severe cortical dysplasia (CD), or CD type II according to Palmini classification, share histopathologic similarities, specifically the presence of cytomegalic neurons and balloon cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20618424", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 758, "text": "This study also provides an opportunity to compare the predictive value of the ILAE and Palmini et al classification schemes with regard to the type I focal cortical dysplasias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1446, "text": "Ten of the 12 patients (83%) who had adequate tissue excised adjacent to the meningioangiomatosis demonstrated evidence of focal cortical dysplasia, with 6 of those (60%) classified as Palmini type IA, and 4 patients (40%) classified as Palmini type IIA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601060", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1732, "text": "Of the 91 patients, there were 50 patients with ILAE focal cortical dysplasia type Ib, 41 with ILAE focal cortical dysplasia type Ic, 63 with Palmini et al focal cortical dysplasia type IA, and 28 with Palmini et al focal cortical dysplasia type IB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "endSection": "abstract" }, { "offsetInBeginSection": 2055, "offsetInEndSection": 2304, "text": "Our findings revealed no significant difference concerning surgical outcome with respect to seizure frequency for the histologic subtypes of ILAE focal cortical dysplasia type I (Ib vs Ic) or Palmini et al focal cortical dysplasia type I (IA vs IB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "endSection": "abstract" }, { "offsetInBeginSection": 1806, "offsetInEndSection": 2078, "text": "Crude analysis revealed no significant difference between patients with subtypes of ILAE focal cortical dysplasia type I or Palmini et al focal cortical dysplasia type I concerning postoperative outcome according to the Engel and ILAE scoring systems on seizure frequency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743217", "endSection": "abstract" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1471, "text": "Since early 2000, the definition of FCD has gradually been given a broader interpretation than the case described by Taylor et al., as shown in Palmini's classification (2004) or the newest classification (2011) proposed by the Neuropathology Task Force of the International League Against Epilepsy (ILAE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23667118", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 390, "text": "Palmini's classification proposed in 2004 is now widely used to categorize FCD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24649461", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 756, "text": "According to Palmini's classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15965699", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 652, "text": "In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 641, "text": "According to Palmini's classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15965699", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 712, "text": "According to Palmini's classification system, the following pathologic subgroups were identified: FCD type IA (3/38), FCD type IB (20/38), FCD type IIA (5/38) and FCD type IIB (5/38). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535679", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1275, "text": "In addition, severe pathologic features (Palmini's classification, FCD type II) (p = 0.025) showed significant correlation with a better surgical outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21275980", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Tuberous sclerosis complex (TSC) and severe cortical dysplasia (CD), or CD type II according to Palmini classification, share histopathologic similarities, specifically the presence of cytomegalic neurons and balloon cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20618424", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1362, "text": "In detail, according to Palmini's classification, mild malformations of cortical development (mMCDs) were disclosed in three patients, focal cortical dysplasia (FCD) type Ia in three patients, and FCD type Ib in five patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22510082", "endSection": "abstract" }, { "offsetInBeginSection": 2293, "offsetInEndSection": 2416, "text": "These results showed considerable improvement compared to a previous study evaluating the 2004 Palmini FCD classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22642611", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 450, "text": "In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 763, "text": "Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23899121", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1200, "text": "Ten of the 12 patients (83%) who had adequate tissue excised adjacent to the meningioangiomatosis demonstrated evidence of focal cortical dysplasia, with 6 of those (60%) classified as Palmini type IA, and 4 patients (40%) classified as Palmini type IIA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601060", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 553, "text": "Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed - from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Tuberous sclerosis complex (TSC) and severe cortical dysplasia (CD), or CD type II according to Palmini classification, share histopathologic similarities, specifically the presence of cytomegalic neurons and balloon cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20618424", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 860, "text": "in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized.Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe.Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844307", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 441, "text": "In contrast to the former FCD classification by Palmini, which considered only histologic features, the novel ILAE classification also relies on magnetic resonance imaging (MRI) findings and presumed pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23551067", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1276, "text": "Since early 2000, the definition of FCD has gradually been given a broader interpretation than the case described by Taylor et al., as shown in Palmini's classification (2004) or the newest classification (2011) proposed by the Neuropathology Task Force of the International League Against Epilepsy (ILAE). The ILAE classification describes 3 types of disease: Type I, Type II, and Type III.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23667118", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 615, "text": "in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844307", "endSection": "abstract" } ] }, { "body": "what is the role of erythropoietin in cardiac regeneration after myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22649318", "http://www.ncbi.nlm.nih.gov/pubmed/17576662", "http://www.ncbi.nlm.nih.gov/pubmed/21258568", "http://www.ncbi.nlm.nih.gov/pubmed/16717399", "http://www.ncbi.nlm.nih.gov/pubmed/16814664", "http://www.ncbi.nlm.nih.gov/pubmed/17239026", "http://www.ncbi.nlm.nih.gov/pubmed/22318706", "http://www.ncbi.nlm.nih.gov/pubmed/19092364", "http://www.ncbi.nlm.nih.gov/pubmed/23137502", "http://www.ncbi.nlm.nih.gov/pubmed/15992646", "http://www.ncbi.nlm.nih.gov/pubmed/17106196", "http://www.ncbi.nlm.nih.gov/pubmed/20849606", "http://www.ncbi.nlm.nih.gov/pubmed/19449462", "http://www.ncbi.nlm.nih.gov/pubmed/22595018", "http://www.ncbi.nlm.nih.gov/pubmed/18827024", "http://www.ncbi.nlm.nih.gov/pubmed/18510486", "http://www.ncbi.nlm.nih.gov/pubmed/18397963" ], "ideal_answer": [ "In preclinical studies, erythropoietin improved cardiac function and perfusion by angiomyogenesis and protection of cardiomyocytes in myocardial infarction indicating that erythropoietin may play a role in the stimulation of cell regeneration under normal physiologic conditions and in patients with myocardial injury. Epo overexpression was found to enhance the cellular regenerative properties of MSCs by both autocrine and paracrine pathways. However, results from recent clinical trials did not support beneficial effects of cytokine therapy with erythropoietin in patients with myocardial infarction." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004921" ], "type": "summary", "id": "52f4f2082059c6d71c00001d", "snippets": [ { "offsetInBeginSection": 1224, "offsetInEndSection": 1377, "text": "EPO in patients with STEMI treated with PCI is associated with an increase in diameter stenosis that is not associated with circulating progenitor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318706", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 322, "text": "The cytokines granulocyte colony-stimulating factor, erythropoietin, and stem cell factor may play a role in helping to stimulate cell regeneration under normal physiologic conditions and in patients with myocardial injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19092364", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 807, "text": "In preclinical study, G-CSF and erythropoietin improved cardiac function and perfusion by angiomyogenesis and protection of cardiomyocytes in myocardial infarction. However, results from recent clinical trials did not support beneficial effects of cytokine therapy with G-CSF or erythropoietin alone in patients with myocardial infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18510486", "endSection": "abstract" }, { "offsetInBeginSection": 1661, "offsetInEndSection": 1775, "text": "Epo overexpression enhances the cellular regenerative properties of MSCs by both autocrine and paracrine pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18397963", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1326, "text": "Transplantation of MSC combined with cytokine EPO is superior to either of the monotherapy approach for angiomyogenesis and cardiac function recovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17239026", "endSection": "abstract" } ] }, { "body": "Does Rad9 interact with Aft1 in S.cerevisiae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25300486" ], "ideal_answer": [ "Yes. Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/RAD9A_HUMAN", "http://www.uniprot.org/uniprot/RAD9_SCHPO", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012441", "http://www.uniprot.org/uniprot/RHNO1_MOUSE", "http://www.uniprot.org/uniprot/RAD9A_MOUSE", "http://www.biosemantics.org/jochem#4263227", "http://www.uniprot.org/uniprot/RAD9_YEAST", "http://www.uniprot.org/uniprot/RAD9B_MOUSE", "http://www.uniprot.org/uniprot/RAD9B_BOVIN", "http://www.uniprot.org/uniprot/RAD9B_RAT", "http://www.uniprot.org/uniprot/NPBL_COPC7", "http://www.uniprot.org/uniprot/RHNO1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029701", "http://www.uniprot.org/uniprot/RAD9B_HUMAN", "http://www.uniprot.org/uniprot/RAD9_SCHOT" ], "type": "yesno", "id": "56b9c937ac7ad10019000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 1376, "text": "Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of \u223c2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 372, "text": "Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 786, "text": "Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ?2% of the coding genome in the absence of exogenously induced DNA damage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486", "endSection": "abstract" }, { "offsetInBeginSection": 786, "offsetInEndSection": 1376, "text": "Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300486", "endSection": "abstract" } ] }, { "body": "Are there any desmins present in plants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18033728", "http://www.ncbi.nlm.nih.gov/pubmed/19026658", "http://www.ncbi.nlm.nih.gov/pubmed/1694790", "http://www.ncbi.nlm.nih.gov/pubmed/20171226", "http://www.ncbi.nlm.nih.gov/pubmed/10929203", "http://www.ncbi.nlm.nih.gov/pubmed/7460905", "http://www.ncbi.nlm.nih.gov/pubmed/12529857", "http://www.ncbi.nlm.nih.gov/pubmed/2659540", "http://www.ncbi.nlm.nih.gov/pubmed/8752741" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0045098", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0005882" } ], "ideal_answer": [ "No. Desmins are type III intermediate filament (IF) proteins that have been identified to date only in metazoa (human, Danio rerio, bovine). Desmins are also associated with severe forms of skeletal, cardiac and myofibrillar myopathies." ], "exact_answer": "no", "concepts": [ "http://www.uniprot.org/uniprot/DESM_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045098" ], "type": "yesno", "id": "5162e011298dcd4e51000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Inherited mutations in the gene coding for the intermediate filament protein desmin have been demonstrated to cause severe skeletal and cardiac myopathies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20171226", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Mutations in the intermediate filament (IF) protein desmin cause severe forms of myofibrillar myopathy characterized by partial aggregation of the extrasarcomeric desmin cytoskeleton and structural disorganization of myofibrils.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026658", "endSection": "sections.0" }, { "offsetInBeginSection": 135, "offsetInEndSection": 479, "text": "The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18033728", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Mutations in desmin have been associated with a subset of human myopathies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12529857", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Characterization of a zebrafish (Danio rerio) desmin cDNA: an early molecular marker of myogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10929203", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Acute effects of desmin mutations on cytoskeletal and cellular integrity in cardiac myocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12529857", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Desmin is a muscle-specific protein and a constitutive subunit of the intermediate filaments (IF) in skeletal, cardiac and smooth muscles. It is an early marker of skeletal muscle myogenesis. We have characterized a clone of desmin cDNA from an embryonic zebrafish (Danio rerio) cDNA library. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10929203", "endSection": "sections.0" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1246, "text": "Immunohistochemical investigation showed a positive reaction for smooth muscle actin and desmins in the spindle cells proliferated in the lymph nodes; no cytokeratin positivity was detected. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8752741", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "We have raised monoclonal antibodies (Mab) to the Mr 55,000 desmin polypeptide, electrophoretically purified from cytoskeletal preparations of isolated bovine heart Purkinje fibers. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1694790", "endSection": "sections.0" }, { "offsetInBeginSection": 237, "offsetInEndSection": 409, "text": "Mesothelial and ovarian carcinoma cells could not be distinguished by (intermediate) filament typing, using monoclonal antibodies (MAbs) to keratins, vimentins and desmins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2659540", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "A fast and convenient procedure for the purification of polymerization-competent smooth-muscle desmin is described. Desmin from chicken gizzard and hog stomach were compared by fingerprint techniques. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7460905", "endSection": "sections.0" } ] }, { "body": "Are viruses involved in the etiology of human subacute thyroiditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18422033", "http://www.ncbi.nlm.nih.gov/pubmed/19138419", "http://www.ncbi.nlm.nih.gov/pubmed/20960165", "http://www.ncbi.nlm.nih.gov/pubmed/11109652", "http://www.ncbi.nlm.nih.gov/pubmed/23227861", "http://www.ncbi.nlm.nih.gov/pubmed/22819125", "http://www.ncbi.nlm.nih.gov/pubmed/19627727", "http://www.ncbi.nlm.nih.gov/pubmed/20671410", "http://www.ncbi.nlm.nih.gov/pubmed/22527824", "http://www.ncbi.nlm.nih.gov/pubmed/1856259", "http://www.ncbi.nlm.nih.gov/pubmed/1691523", "http://www.ncbi.nlm.nih.gov/pubmed/18421188", "http://www.ncbi.nlm.nih.gov/pubmed/12608662", "http://www.ncbi.nlm.nih.gov/pubmed/22459018", "http://www.ncbi.nlm.nih.gov/pubmed/20886354", "http://www.ncbi.nlm.nih.gov/pubmed/9790279", "http://www.ncbi.nlm.nih.gov/pubmed/10971829", "http://www.ncbi.nlm.nih.gov/pubmed/4936649", "http://www.ncbi.nlm.nih.gov/pubmed/10525005", "http://www.ncbi.nlm.nih.gov/pubmed/22136271", "http://www.ncbi.nlm.nih.gov/pubmed/15332726", "http://www.ncbi.nlm.nih.gov/pubmed/16279854", "http://www.ncbi.nlm.nih.gov/pubmed/9915102" ], "ideal_answer": [ "Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid caused probably by viruses\nThe principal classes of viruses involed in SAT include Epstein Barr and Retroviridae" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014780", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050033", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013190", "http://www.disease-ontology.org/api/metadata/DOID:7187", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003831", "http://www.disease-ontology.org/api/metadata/DOID:7166", "http://www.disease-ontology.org/api/metadata/DOID:7165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007453", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013962", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013958", "http://www.uniprot.org/uniprot/PERT_RAT", "http://www.uniprot.org/uniprot/PERT_CANFA", "http://www.uniprot.org/uniprot/PERT_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013966", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013968", "http://www.uniprot.org/uniprot/PERT_PIG", "http://www.uniprot.org/uniprot/PERT_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013957" ], "type": "yesno", "id": "513711055274a5fb0700000e", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 180, "text": "he etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1856259", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. I", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11109652", "endSection": "sections.0" }, { "offsetInBeginSection": 713, "offsetInEndSection": 853, "text": "We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11109652", "endSection": "sections.0" }, { "offsetInBeginSection": 711, "offsetInEndSection": 1051, "text": "ltogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1691523", "endSection": "sections.0" } ] }, { "body": "List core circadian clock genes.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24919398", "http://www.ncbi.nlm.nih.gov/pubmed/24378737", "http://www.ncbi.nlm.nih.gov/pubmed/25045881", "http://www.ncbi.nlm.nih.gov/pubmed/25013953", "http://www.ncbi.nlm.nih.gov/pubmed/24454829", "http://www.ncbi.nlm.nih.gov/pubmed/25888034", "http://www.ncbi.nlm.nih.gov/pubmed/26131842", "http://www.ncbi.nlm.nih.gov/pubmed/25025868" ], "ideal_answer": [ "The core circadian clock genes are CLOCK, BMAL1, Per, and Cry." ], "exact_answer": [ [ "CLOCK" ], [ "BMAL1" ], [ "Per" ], [ "Cry" ], [ "CKl\u03b5" ] ], "type": "list", "id": "56e30dd551531f7e33000016", "snippets": [ { "offsetInBeginSection": 816, "offsetInEndSection": 857, "text": "PER1, CRY1, CRY2, CLOCK, BMAL1, and CKl\u03b5 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26131842", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 687, "text": " Expression levels of five clock genes (Rev-Erb\u03b1, Per1, Per2, Bmal1 and Cry1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25045881", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 584, "text": "altered expression patterns of the circadian clock genes, Bmal1 and Per2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888034", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 741, "text": "This review will focus on the core circadian clock genes CLOCK, BMAL1, Per, and Cry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25025868", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1012, "text": "CLOCK, RORA, and NPAS2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24919398", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1204, "text": "Rev-erb\u03b1 and Bmal1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25013953", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1407, "text": "he core circadian clock genes BMAL1, PER1/2 and CRY1/2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24454829", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 360, "text": "CLOCK/BMAL1, the core circadian clock components", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24378737", "endSection": "abstract" } ] }, { "body": "Which peripheral neuropathy has been associated with NDRG1 mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20582309", "http://www.ncbi.nlm.nih.gov/pubmed/15082788", "http://www.ncbi.nlm.nih.gov/pubmed/12884740", "http://www.ncbi.nlm.nih.gov/pubmed/15651351", "http://www.ncbi.nlm.nih.gov/pubmed/12872253", "http://www.ncbi.nlm.nih.gov/pubmed/16541790", "http://www.ncbi.nlm.nih.gov/pubmed/23996628", "http://www.ncbi.nlm.nih.gov/pubmed/21303696" ], "ideal_answer": [ "Charcot-Marie-Tooth (CMT) 4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1).", "CMT4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1)" ], "exact_answer": [ "Charcot-Marie-Tooth (CMT) 4D disease" ], "type": "factoid", "id": "5713c8d71174fb1755000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "CMT4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "In a previous study, we have shown that N-myc downstream-regulated gene 1 (NDRG1), classified in databases as a tumor suppressor and heavy metal-response protein, is mutated in hereditary motor and sensory neuropathy Lom (HMSNL), a severe autosomal recessive form of Charcot-Marie-Tooth (CMT) disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12872253", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 1289, "text": "In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1093, "text": "The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582309", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1598, "text": "Genetic studies have revealed the following gene mutations as the causes of inherited neuropathies; PMP22, MPZ, EGR2, SOX10, SIMPLE/LITAF, ARHGEF10 for CMT1 (autosomal dominant demyelinating form); GDAP1, MTMR2, SBF2/MTMR13, KIAA1985, NDRG1 PRX for CMT4 (autosomal recessive demyelinating form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 for CMT-DI (autosomal dominant CMT with intermediate nerve conduction velocities); and DHH for minifascicular neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16541790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "In a previous study, we have shown that N-myc downstream-regulated gene 1 (NDRG1), classified in databases as a tumor suppressor and heavy metal-response protein, is mutated in hereditary motor and sensory neuropathy Lom (HMSNL), a severe autosomal recessive form of Charcot-Marie-Tooth (CMT) disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12872253", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 702, "text": "Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "CMT4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303696", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1252, "text": "The success of molecular genetic analysis in all families confirms that autosomal recessive forms of CMT caused by mutations on the NDRG1 and HK1 genes are common causes of inherited neuropathies among Slovak Roma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23996628", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 441, "text": "Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 616, "text": "In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2. In the primary peripheral axonal neuropathies (CMT2), at least 10 genes have been associated with these disorders; NEFL, KIF1B, MFN2, GAN1, LMNA, RAB7, GARS, TDP1, APTX, and SETX.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15651351", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 1018, "text": "In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1). In the primary peripheral axonal neuropathies(CMT2), at least 8 genes have been associated with these disorders; the neurofilament light chain gene(NEFL), the kinesin 1B gene(KIF1B), the gigaxonin gene(GAN1), Lamin A/C(LMNA) and tyrosyl-DNA phosphodiesterase 1(TDP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": " NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 750, "text": "Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 436, "text": "Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15651351", "endSection": "abstract" }, { "offsetInBeginSection": 1428, "offsetInEndSection": 1825, "text": "Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582309", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 436, "text": "In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15651351", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 947, "text": "The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582309", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 750, "text": "In the primary peripheral demyelinating neuropathies(CMT1), at least 9 genes have been associated with the disorders; altered dosage of peripheral myelin protein 22(PMP22) or point mutation of PMP22, the gap junction protein 1(GJB1), the myelin protein zero gene(MPZ), the early growth response gene 2(EGR2), the myotubularin-related protein 2 gene(MTMR2), the N-myc downstream-regulated gene 1 (NDRG1), the L-periaxin gene(PRX), SRY-related HMG-BOX gene 10(SOX10) and the ganglioside-induced differentiation-associated protein 1 gene(GDAP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12884740", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 441, "text": "Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082788", "endSection": "abstract" } ] }, { "body": "Is miR-126 involved in heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21157109", "http://www.ncbi.nlm.nih.gov/pubmed/23465244" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A11659990", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1537773", "o": "http://linkedlifedata.com/resource/umls/label/A11659990" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17697100", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17400039", "o": "mmu-mir-126" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2741955", "o": "http://linkedlifedata.com/resource/umls/label/A17400039" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2825936", "o": "http://linkedlifedata.com/resource/umls/label/A17697100" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2351954", "o": "http://linkedlifedata.com/resource/umls/label/A15584100" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A15584100", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17399048", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2934296", "o": "http://linkedlifedata.com/resource/umls/label/A18459725" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18459725", "o": "miR-126, zebrafish" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16480760", "o": "hsa-mir-126 microRNA" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0018801", "o": "http://linkedlifedata.com/resource/umls/label/A0418144" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0418144", "o": "HEART FAILURE" } ], "ideal_answer": [ "Yes, miR-126 is associated with heart failure." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003015", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.disease-ontology.org/api/metadata/DOID:114" ], "type": "yesno", "id": "51485008d24251bc05000028", "snippets": [ { "offsetInBeginSection": 1479, "offsetInEndSection": 1714, "text": "he miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23465244", "endSection": "sections.0" }, { "offsetInBeginSection": 1099, "offsetInEndSection": 1236, "text": "The plasma concentration of miR-126 was negatively correlated with age and NYHA class, and could be a useful biomarker for heart failure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21157109", "endSection": "sections.0" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1085, "text": "In 10 patients with heart failure, plasma concentrations of miR-126 were up-regulated with improvement of the NYHA class from IV to III.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21157109", "endSection": "sections.0" } ] }, { "body": "Does resveratrol reduce cardiac remodeling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22926332", "http://www.ncbi.nlm.nih.gov/pubmed/22473781", "http://www.ncbi.nlm.nih.gov/pubmed/20869962", "http://www.ncbi.nlm.nih.gov/pubmed/23274061", "http://www.ncbi.nlm.nih.gov/pubmed/18853243", "http://www.ncbi.nlm.nih.gov/pubmed/19370079", "http://www.ncbi.nlm.nih.gov/pubmed/18310510", "http://www.ncbi.nlm.nih.gov/pubmed/16198371", "http://www.ncbi.nlm.nih.gov/pubmed/18356487", "http://www.ncbi.nlm.nih.gov/pubmed/20874677", "http://www.ncbi.nlm.nih.gov/pubmed/20491649", "http://www.ncbi.nlm.nih.gov/pubmed/22050707", "http://www.ncbi.nlm.nih.gov/pubmed/12679191", "http://www.ncbi.nlm.nih.gov/pubmed/18639559", "http://www.ncbi.nlm.nih.gov/pubmed/20675566", "http://www.ncbi.nlm.nih.gov/pubmed/19460403", "http://www.ncbi.nlm.nih.gov/pubmed/19370081", "http://www.ncbi.nlm.nih.gov/pubmed/20429690", "http://www.ncbi.nlm.nih.gov/pubmed/21352470", "http://www.ncbi.nlm.nih.gov/pubmed/17488730", "http://www.ncbi.nlm.nih.gov/pubmed/20008278", "http://www.ncbi.nlm.nih.gov/pubmed/19942861", "http://www.ncbi.nlm.nih.gov/pubmed/19959541", "http://www.ncbi.nlm.nih.gov/pubmed/18562309", "http://www.ncbi.nlm.nih.gov/pubmed/21054406", "http://www.ncbi.nlm.nih.gov/pubmed/17875610", "http://www.ncbi.nlm.nih.gov/pubmed/22245452", "http://www.ncbi.nlm.nih.gov/pubmed/22768138", "http://www.ncbi.nlm.nih.gov/pubmed/15498824", "http://www.ncbi.nlm.nih.gov/pubmed/23784505", "http://www.ncbi.nlm.nih.gov/pubmed/24289075", "http://www.ncbi.nlm.nih.gov/pubmed/22229508", "http://www.ncbi.nlm.nih.gov/pubmed/20716127" ], "ideal_answer": [ "Resveratrol attenuates left ventricular remodeling.\nResveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the postinfarction heart.\nResveratrol administration improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function.\nResveratrol can constitute an adjuvant therapeutic option in prevention of dilated cardiomyopathy.", "Most of the evidence shows that Resveratrol supresses cardiac remodeling." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4272358", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064752", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006332", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003015", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002306" ], "type": "yesno", "id": "52e7bbf698d023950500001d", "snippets": [ { "offsetInBeginSection": 1199, "offsetInEndSection": 1498, "text": "In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289075", "endSection": "abstract" }, { "offsetInBeginSection": 1547, "offsetInEndSection": 1697, "text": "In conclusion, resveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the postinfarction heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23274061", "endSection": "abstract" }, { "offsetInBeginSection": 1794, "offsetInEndSection": 2214, "text": "Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768138", "endSection": "abstract" } ] }, { "body": "Which is the receptor for substrates of Chaperone Mediated Autophagy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18635949", "http://www.ncbi.nlm.nih.gov/pubmed/22331875", "http://www.ncbi.nlm.nih.gov/pubmed/15331765", "http://www.ncbi.nlm.nih.gov/pubmed/22426402", "http://www.ncbi.nlm.nih.gov/pubmed/11208145", "http://www.ncbi.nlm.nih.gov/pubmed/11082038", "http://www.ncbi.nlm.nih.gov/pubmed/22809326", "http://www.ncbi.nlm.nih.gov/pubmed/19117012", "http://www.ncbi.nlm.nih.gov/pubmed/18644871", "http://www.ncbi.nlm.nih.gov/pubmed/21429245", "http://www.ncbi.nlm.nih.gov/pubmed/23070014", "http://www.ncbi.nlm.nih.gov/pubmed/23404999", "http://www.ncbi.nlm.nih.gov/pubmed/21966475", "http://www.ncbi.nlm.nih.gov/pubmed/12505983", "http://www.ncbi.nlm.nih.gov/pubmed/18927485", "http://www.ncbi.nlm.nih.gov/pubmed/19433452", "http://www.ncbi.nlm.nih.gov/pubmed/21514572", "http://www.ncbi.nlm.nih.gov/pubmed/15325583", "http://www.ncbi.nlm.nih.gov/pubmed/18550537", "http://www.ncbi.nlm.nih.gov/pubmed/17284523", "http://www.ncbi.nlm.nih.gov/pubmed/16585521", "http://www.ncbi.nlm.nih.gov/pubmed/10806201", "http://www.ncbi.nlm.nih.gov/pubmed/22227450", "http://www.ncbi.nlm.nih.gov/pubmed/22363588", "http://www.ncbi.nlm.nih.gov/pubmed/22653298" ], "ideal_answer": [ "Chaperone-mediated autophagy (CMA) is a lysosomal pathway for selective removal of damaged cytosolic proteins. The LAMP2A (Lysosome-associated membrane protein 2 isoform A) functions as a receptor for cytosolic proteins and also as essential component of the CMA translocation complex [28]. Cytosolic substrate proteins bind to monomers of LAMP-2A, which then multimerizes to form the complex required for substrate transmembrane import." ], "exact_answer": [ "LAMP2A", "Lysosome-associated membrane protein 2 isoform A" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006914", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0072321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018832", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004872", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008565", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0038024" ], "type": "factoid", "id": "51bdd9c2047fa84d1d000002", "snippets": [ { "offsetInBeginSection": 149, "offsetInEndSection": 346, "text": "These proteins are targeted by chaperones and delivered to lysosomes where they are translocated into the lysosomal lumen and degraded via the lysosome-associated membrane protein type 2A (LAMP-2A)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404999", "endSection": "sections.0" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1432, "text": "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23070014", "endSection": "sections.0" }, { "offsetInBeginSection": 671, "offsetInEndSection": 756, "text": "CMA activity has been shown to be proportional to levels of the CMA receptor Lamp-2a.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426402", "endSection": "sections.0" }, { "offsetInBeginSection": 747, "offsetInEndSection": 900, "text": "Lysosomes from livers of lipid-challenged mice had a marked decrease in the levels of the CMA receptor, the lysosome-associated membrane protein type 2A,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22331875", "endSection": "sections.0" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1171, "text": "We report that Bcl-2-related early rod apoptosis was associated with the upregulation of autophagy markers including chaperone-mediated autophagy (CMA) substrate receptor LAMP-2", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22227450", "endSection": "sections.0" }, { "offsetInBeginSection": 617, "offsetInEndSection": 710, "text": "we examined gene expression levels of lysosome-associated membrane 2 (LAMP-2), a CMA receptor", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21514572", "endSection": "sections.0" }, { "offsetInBeginSection": 110, "offsetInEndSection": 236, "text": "The lysosomal-membrane protein type 2A (LAMP-2A) acts as the receptor for the substrates of chaperone-mediated autophagy (CMA)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18927485", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Chaperone-mediated autophagy (CMA) is a selective type of autophagy by which specific cytosolic proteins are sent to lysosomes for degradation. Substrate proteins bind to the lysosomal membrane through the lysosome-associated membrane protein type 2A (LAMP-2A), one of the three splice variants of the lamp2 gene, and this binding is limiting for their degradation via CMA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18644871", "endSection": "sections.0" }, { "offsetInBeginSection": 662, "offsetInEndSection": 837, "text": "Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18644871", "endSection": "sections.0" }, { "offsetInBeginSection": 266, "offsetInEndSection": 394, "text": "We recently reported that UCH-L1 physically interacts with LAMP-2A, the lysosomal receptor for chaperone-mediated autophagy (CMA", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18635949", "endSection": "sections.0" }, { "offsetInBeginSection": 460, "offsetInEndSection": 562, "text": "In this study, we found that UCH-L1 physically interacts with LAMP-2A, the lysosomal receptor for CMA,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18550537", "endSection": "sections.0" }, { "offsetInBeginSection": 113, "offsetInEndSection": 406, "text": "We have previously described an age-related decline in chaperone-mediated autophagy (CMA), a selective form of autophagy, by which particular cytosolic proteins are delivered to lysosomes after binding to the lysosome-associated membrane protein type 2A (LAMP-2A), a receptor for this pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17284523", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Chaperone-mediated autophagy (CMA) is a selective pathway for the degradation of cytosolic proteins in lysosomes. CMA declines with age because of a decrease in the levels of lysosome-associated membrane protein (LAMP) type 2A, a lysosomal receptor for this pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16585521", "endSection": "sections.0" }, { "offsetInBeginSection": 543, "offsetInEndSection": 853, "text": "Oxidation-induced activation of CMA correlates with higher levels of several components of the lysosomal translocation complex, but in particular of the lumenal chaperone, required for substrate uptake, and of the lysosomal membrane protein (lamp) type 2a, previously identified as a receptor for this pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15331765", "endSection": "sections.0" }, { "offsetInBeginSection": 112, "offsetInEndSection": 296, "text": "We now demonstrate that this protease activity triggers the degradation of the lysosome-associated membrane protein type 2a (lamp2a), a receptor for chaperone-mediated autophagy (CMA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12505983", "endSection": "sections.0" }, { "offsetInBeginSection": 185, "offsetInEndSection": 289, "text": "We have previously identified this receptor as the lysosome-associated membrane protein type 2a (lamp2a)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11208145", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11082038", "endSection": "sections.0" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1111, "text": "These characteristics may be important for lamp2a to act as a receptor for chaperone-mediated autophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11082038", "endSection": "sections.0" }, { "offsetInBeginSection": 603, "offsetInEndSection": 760, "text": "A progressive age-related decrease in the levels of the lysosome-associated membrane protein type 2a that acts as a receptor for chaperone-mediated autophagy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10806201", "endSection": "sections.0" }, { "offsetInBeginSection": 584, "offsetInEndSection": 736, "text": "Hsc70 and Hsp40 are members of a molecular chaperone complex required for protein transport into the lysosome during chaperone-mediated autophagy (CMA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117012", "endSection": "sections.0" }, { "offsetInBeginSection": 430, "offsetInEndSection": 696, "text": "Once there, substrate proteins bind to the lysosome-associated membrane protein type 2 isoform A (LAMP2A), inducing assembly of this receptor protein into a higher molecular weight protein complex that is used by the substrate proteins to reach the lysosomal lumen. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22653298", "endSection": "sections.0" }, { "offsetInBeginSection": 428, "offsetInEndSection": 549, "text": "Protein substrates bind to a receptor in the lysosomal membrane, the lysosome-associated membrane protein (lamp) type 2a.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15325583", "endSection": "sections.0" } ] }, { "body": "What are the hallmarks of congestive heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12691636", "http://www.ncbi.nlm.nih.gov/pubmed/7777669", "http://www.ncbi.nlm.nih.gov/pubmed/22707076", "http://www.ncbi.nlm.nih.gov/pubmed/17922627", "http://www.ncbi.nlm.nih.gov/pubmed/19808348", "http://www.ncbi.nlm.nih.gov/pubmed/1357906", "http://www.ncbi.nlm.nih.gov/pubmed/2936238", "http://www.ncbi.nlm.nih.gov/pubmed/9519348", "http://www.ncbi.nlm.nih.gov/pubmed/11930867" ], "ideal_answer": [ "Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid. Common pathophysiologic features of HF include changes in left ventricle structure, function, and neurohormonal activation. Disturbed myocardial calcium handling is also one of the pathophysiologic hallmarks of congestive heart failure. One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart. It has been proposed that the activation of neurohormonal pathways and the formation of oxygen free radicals ultimately lead to the activation of a family of transcription factors that are involved in cardiac and vascular remodelling which are hallmarks of congestive heart failure. Myocardial failure ultimately leads to exaggerated neurohumoral compensatory mechanisms and derangements of the peripheral circulation, which are the hallmarks of congestive heart failure. Two additional hallmarks of this syndrome are sodium and water retention. Accumulation of oxidized matrix between the endothelium and cardiac muscle, and endocardial endothelial dysfunction, are also hallmarks of congestive heart failure." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:6000" ], "type": "summary", "id": "54d892ee014675820d000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Disturbed myocardial calcium (Ca(+)) handling is one of the pathophysiologic hallmarks of cardiovascular diseases such as congestive heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808348", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 435, "text": "Common pathophysiologic features of HF include changes in left ventricle structure, function, and neurohormonal activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808348", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 831, "text": "the compensatory neurohormonal systems and ventricular remodeling that are the hallmarks of CHF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11930867", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 361, "text": "The most important processes to be activated in heart failure are the neurohormonal systems, which include the reninangiotensin system, the sympathetic nervous system and the endothelin system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9519348", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 492, "text": "the formation of reactive oxygen free radicals is increased in congestive heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9519348", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 775, "text": "It has been proposed that the activation of neurohormonal pathways and the formation of oxygen free radicals ultimately lead to the activation of a family of transcription factors that are involved in cardiac and vascular remodelling which are hallmarks of congestive heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9519348", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 560, "text": "Myocardial failure ultimately leads to exaggerated neurohumoral compensatory mechanisms and derangements of the peripheral circulation, which are the hallmarks of congestive heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2936238", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 183, "text": "The two hallmarks of this syndrome, sodium and water retention, are frequently a therapeutic challenge.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17922627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Accumulation of oxidized matrix between the endothelium and cardiac muscle, and endocardial endothelial dysfunction, are the hallmarks of congestive heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12691636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart. A correlation between plasma norepinephrine and the severity of the heart failure state has been demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7777669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Disturbed myocardial calcium (Ca(+)) handling is one of the pathophysiologic hallmarks of cardiovascular diseases such as congestive heart failure, cardiac hypertrophy, and certain types of tachyarrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707076", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 559, "text": "Myocardial failure ultimately leads to exaggerated neurohumoral compensatory mechanisms and derangements of the peripheral circulation, which are the hallmarks of congestive heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2936238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7777669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Myocardial pump deficiency is regarded to be the hemodynamic hallmark of congestive heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1357906", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of short QT syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19829181", "http://www.ncbi.nlm.nih.gov/pubmed/16812977", "http://www.ncbi.nlm.nih.gov/pubmed/19482666" ], "ideal_answer": [ "The short QT syndrome has an autosomal dominant mode of inheritance." ], "exact_answer": [ "autosomal dominant mode of inheritance" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918" ], "type": "factoid", "id": "52f509512059c6d71c000020", "snippets": [ { "offsetInBeginSection": 259, "offsetInEndSection": 552, "text": "Congenital short QT syndrome is a new familial primary electrical disease of the heart, which is characterized by abnormally short QT interval and paroxysmal atrial and ventricular tachyarrhythmias, including sudden cardiac death. An autosomal dominant mode of inheritance has been suggested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19482666", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 924, "text": "From 1993, the Short QT Syndrome (SQTS) came to our attention, as a new inherited \"electrical disease\" associated with increased risk of sudden cardiac death and atrial fibrillation. Mutations of Ikr, Iks, Ikl channels cause dysfunctional Iks, Ikr, Ikl channels with an increase in the net outward K current leading to shortening of repolarization. This in turn leads to a shorter QT interval on the ECG and shorter atrial and ventricular refractory periods with increased susceptibility to VF and AF. There seems to be an autosomal dominant mode of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16812977", "endSection": "abstract" } ] }, { "body": "List clinical trials that have directly compared microsurgical clipping with endovascular coiling for treatment of ruptured brain aneurysms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20808697", "http://www.ncbi.nlm.nih.gov/pubmed/17703631", "http://www.ncbi.nlm.nih.gov/pubmed/18053204", "http://www.ncbi.nlm.nih.gov/pubmed/16172968", "http://www.ncbi.nlm.nih.gov/pubmed/21947244", "http://www.ncbi.nlm.nih.gov/pubmed/19329361", "http://www.ncbi.nlm.nih.gov/pubmed/23621600", "http://www.ncbi.nlm.nih.gov/pubmed/23607065", "http://www.ncbi.nlm.nih.gov/pubmed/21898188", "http://www.ncbi.nlm.nih.gov/pubmed/16139655", "http://www.ncbi.nlm.nih.gov/pubmed/23049642", "http://www.ncbi.nlm.nih.gov/pubmed/23964263", "http://www.ncbi.nlm.nih.gov/pubmed/12414200", "http://www.ncbi.nlm.nih.gov/pubmed/21696651", "http://www.ncbi.nlm.nih.gov/pubmed/20165722", "http://www.ncbi.nlm.nih.gov/pubmed/23210044" ], "ideal_answer": [ "Barrow Ruptured Aneurysm Trial (BRAT) and international subarachnoid aneurysmal trial (ISAT) have directly compared microsurgical clipping with endovascular coiling for treatment of ruptured brain aneurysms. FIAT study, a clinical care trial aiming to compare angiographic and clinical outcomes following treatment with a Flow-Diverter or with the best conventional treatment option (including clipping) is underway." ], "exact_answer": [ [ "Barrow Ruptured Aneurysm Trial (BRAT)" ], [ "international subarachnoid aneurysmal trial (BRAT)" ], [ "FIAT study" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013525", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000783", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002532", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017542", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986" ], "type": "list", "id": "530e0d6e5937551c09000001", "snippets": [ { "offsetInBeginSection": 8, "offsetInEndSection": 377, "text": "The authors report the 3-year results of the Barrow Ruptured Aneurysm Trial (BRAT). The objective of this ongoing randomized trial is to compare the safety and efficacy of microsurgical clip occlusion and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to compare functional outcomes based on clinical and angiographic data. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621600", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 973, "text": "We report the design of the FIAT study, a clinical care trial aiming to compare angiographic and clinical outcomes following treatment with a Flow-Diverter or with the best conventional treatment option. The FIAT study will include both a randomized and a registry portion. Patients will be proposed randomization to either FD stenting or best conventional treatment option (observation, coiling, stenting, or clipping) as determined by the treating physician. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21696651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The effect of clipping and coiling in acute severe subarachnoid hemorrhage after international subarachnoid aneurysmal trial (ISAT) results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16172968", "endSection": "title" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1534, "text": "A critical appraisal of the ISAT of microsurgical clipping versus coiling is used for comparison of our results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16172968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16139655", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12414200", "endSection": "title" } ] }, { "body": "What is the reason for the narcolepsy cases developed after H1N1 influenza vaccination?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21866560", "http://www.ncbi.nlm.nih.gov/pubmed/23486871", "http://www.ncbi.nlm.nih.gov/pubmed/24048081", "http://www.ncbi.nlm.nih.gov/pubmed/23884811", "http://www.ncbi.nlm.nih.gov/pubmed/21963829", "http://www.ncbi.nlm.nih.gov/pubmed/21676420", "http://www.ncbi.nlm.nih.gov/pubmed/22530521", "http://www.ncbi.nlm.nih.gov/pubmed/22213222" ], "ideal_answer": [ "The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014611", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053118", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014612", "http://www.disease-ontology.org/api/metadata/DOID:8986", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009290" ], "type": "summary", "id": "530cf54dab4de4de0c000009", "snippets": [ { "offsetInBeginSection": 747, "offsetInEndSection": 957, "text": "The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24048081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes narcolepsy with cataplexy. An autoimmune basis for the disease has long been suspected and recent results have greatly strengthened this hypothesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963829", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 776, "text": "pointing towards processes such as molecular mimicry or bystander activation as crucial for disease development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963829", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 840, "text": "Although no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1\u00a0vaccination in susceptible individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21676420", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1251, "text": "Pandemrix vaccination is a precipitating factor for narcolepsy, especially in combination with HLA-DQB1*0602. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23486871", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 524, "text": "Recently identified autoantibodies to Tribbles homologue 2 in some patients, as well as cases associated with H1N1 vaccination, support an autoimmune mechanism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22213222", "endSection": "abstract" }, { "offsetInBeginSection": 1367, "offsetInEndSection": 1701, "text": "n China, narcolepsy onset is highly correlated with seasonal and annual patterns of upper airway infections, including H1N1 influenza. In 2010, the peak seasonal onset of narcolepsy was phase delayed by 6 months relative to winter H1N1 infections, and the correlation was independent of H1N1 vaccination in the majority of the sample.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21866560", "endSection": "abstract" }, { "offsetInBeginSection": 2016, "offsetInEndSection": 2141, "text": "H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23884811", "endSection": "abstract" } ] }, { "body": "Which are the biotracers used for detection of Alzheimer's disease using PET?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22982358", "http://www.ncbi.nlm.nih.gov/pubmed/23966249", "http://www.ncbi.nlm.nih.gov/pubmed/23624169", "http://www.ncbi.nlm.nih.gov/pubmed/23882370", "http://www.ncbi.nlm.nih.gov/pubmed/20580647", "http://www.ncbi.nlm.nih.gov/pubmed/24166579", "http://www.ncbi.nlm.nih.gov/pubmed/23527322", "http://www.ncbi.nlm.nih.gov/pubmed/24194552", "http://www.ncbi.nlm.nih.gov/pubmed/21683932", "http://www.ncbi.nlm.nih.gov/pubmed/24199960", "http://www.ncbi.nlm.nih.gov/pubmed/17182990", "http://www.ncbi.nlm.nih.gov/pubmed/21624562", "http://www.ncbi.nlm.nih.gov/pubmed/23966257", "http://www.ncbi.nlm.nih.gov/pubmed/23420460", "http://www.ncbi.nlm.nih.gov/pubmed/18620875", "http://www.ncbi.nlm.nih.gov/pubmed/18191617", "http://www.ncbi.nlm.nih.gov/pubmed/15783264", "http://www.ncbi.nlm.nih.gov/pubmed/23597030", "http://www.ncbi.nlm.nih.gov/pubmed/23178035", "http://www.ncbi.nlm.nih.gov/pubmed/23995816", "http://www.ncbi.nlm.nih.gov/pubmed/16712496", "http://www.ncbi.nlm.nih.gov/pubmed/21764791", "http://www.ncbi.nlm.nih.gov/pubmed/24132372", "http://www.ncbi.nlm.nih.gov/pubmed/23536396", "http://www.ncbi.nlm.nih.gov/pubmed/19142702", "http://www.ncbi.nlm.nih.gov/pubmed/19164222", "http://www.ncbi.nlm.nih.gov/pubmed/23053137" ], "ideal_answer": [ "Pittsburgh compound B (PIB) was the first radiotracer capable of highlighting deposits of beta-amyloid\u2014one pathological hallmark of Alzheimer's disease\u2014in living individuals during a PET scan. The Alzheimer's Association helped fund early PIB development. The Association in 2006 also awarded a $2.1 million grant to the Alzheimer's Disease Neuroimaging Initiative (ADNI) to expand this long-term, nationwide study to include PIB-PET imaging.\n\n18F flutemetamol (flute), another radiotracer that highlights beta-amyloid in a PET scan, is structurally identical to PIB except for one fluorine atom in place of a carbon atom. That small chemical change enables flutemetamol to remain stable significantly longer than does PIB, potentially increasing its usefulness outside research settings. In phase II study results reported in the Annals of Neurology, flutemetamol performed similarly to PIB. Additional testing is under way.\n\nFlorbetapir F 18 (18F-AV-45) is also a radiotracer that highlights brain beta-amyloid during a PET scan. At the 2010 Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD), florbetapir's developer first reported data, later published in the JAMA, showing nearly perfect correlation between brain amyloid levels detected by florbetapir PET scans in study volunteers and levels found in autopsies of the same individuals a few months later. The developer has sought Food and Drug Administration (FDA) approval to market florbetapir under the brand name Amyvid. The FDA has said it will withhold approval until the developer establishes a professional training program to ensure accuracy and consistency in reading and interpreting Amyvid scans.\n\nFlorbetaben (BAY 94-9172) is another radiotracer designed to detect beta-amyloid during a PET scan. Phase II study results and other florbetaben data were reported at the 2010 Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD). Phase II data were also later published in Lancet Neurology. Further studies are now under way." ], "exact_answer": [ [ "Pittsburgh compound B" ], [ "Florbetaben (BAY 94-9172)" ], [ "Florbetapir F 18 (18F-AV-45)" ], [ "18F flutemetamol (flute)" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019788", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "list", "id": "5311bf53e3eabad021000006", "snippets": [ { "offsetInBeginSection": 1292, "offsetInEndSection": 1512, "text": "(18)F-flutemetamol PET and structural MRI provided additive information in the diagnostic classification of aMCI subjects, suggesting an amyloid-independent neurodegenerative component among aMCI subjects in this sample.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23178035", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 435, "text": "This pooled analysis of four studies determined the level of association between uptake of the fibrillar amyloid \u03b2 positron emission tomography (PET) imaging agent [(18)F]flutemetamol (Pittsburgh Compound B analog with a 5.5 times longer half-life to enable it to be used in the clinical setting) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053137", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 557, "text": "is implicated in the development of late-onset Alzheimer's disease (AD). We sought to determine the associations between beta amyloid (A\u03b2) plaque deposition in vivo using Pittsburgh compound B (PiB) and several indices of cholesterol homeostasis (i.e., total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein E (ApoE), clusterin, oxysterol metabolites of cholesterol, and previously reported genes associated with late-onset AD) in 175 nondemented elderly subjects. High A\u03b2 dep", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24199960", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 406, "text": "g biomarkers of Alzheimer's disease include amyloid deposition [imaged with [(11)C]Pittsburgh compound B (PiB) PET], altered glucose metabolism (imaged with [(18)F]fluro-deoxyglucose PET), and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer's disease. We now exte", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194552", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 428, "text": "Criteria for preclinical Alzheimer disease (AD) propose \u03b2-amyloid (A\u03b2) plaques to initiate neurodegeneration within AD-affected regions. However, some cognitively normal older individuals harbor neural injury similar to patients with AD, without concurrent A\u03b2 burden. Such findings challenge the proposed sequence and suggest that A\u03b2-independent precursors underlie AD-typical neurodegenerative patterns. OBJECTIVE T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24166579", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 1814, "text": "ol is a positron emission tomography (PET) tracer for in vivo amyloid imaging. The ability to classify amyloid scans in a binary manner as 'normal' versus 'Alzheimer-like', is of high clinical relevance. We evaluated whether a supervised machine learning technique, support vector machines (SVM), can replicate the assignments made by visual readers blind to the clinical diagnosis, which image components have highest diagnostic value according to SVM and how (18)F-flutemetamol-based classification using SVM relates to structural MRI-based classification using SVM within the same subjects. By means of SVM with a linear kernel, we analyzed (18)F-flutemetamol scans and volumetric MRI scans from 72 cases from the (18)F-flutemetamol phase 2 study (27 clinically probable Alzheimer's disease (AD), 20 amnestic mild cognitive impairment (MCI), 25 controls). In a leave-one-out approach, we trained the (18)F-flutemetamol based classifier by means of the visual reads and tested whether the classifier was able to reproduce the assignment based on visual reads and which voxels had the highest feature weights. The (18)F-flutemetamol based classifier was able to replicate the assignments obtained by visual reads with 100% accuracy. The voxels with highest feature weights were in the striatum, precuneus, cingulate and middle frontal gyrus. Second, to determine concordance between the gray matter volume- and the (18)F-flutemetamol-based classification, we trained the classifier with the clinical diagnosis as gold standard. Overall sensitivity of the (18)F-flutemetamol- and the gray matter volume-based classifiers were identical (85.2%), albeit with discordant classification in three cases. Specificity of the (18)F-flutemetamol based classifier was 92% compared to 68% for MRI. In the MCI ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982358", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1598, "text": "disease (AD) is defined histologically by the presence of extracellular \u03b2-amyloid (A\u03b2) plaques and intraneuronal neurofibrillary tangles in the cerebral cortex. The diagnosis of dementia, along with the prediction of who will develop dementia, has been assisted by magnetic resonance imaging and positron emission tomography (PET) by using [(18)F]fluorodeoxyglucose (FDG). These techniques, however, are not specific for AD. Based on the chemistry of histologic staining dyes, several A\u03b2-specific positron-emitting radiotracers have been developed to image neuropathology of AD. Among these, [(11)C]PiB is the most studied A\u03b2-binding PET radiopharmaceutical in the world. The histologic and biochemical specificity of PiB binding across different regions of the AD brain was demonstrated by showing a direct correlation between A\u03b2-containing amyloid plaques and in vivo [(11)C]PiB retention measured by PET imaging. Because (11)C is not ideal for commercialization, several (18)F-labeled tracers have been developed. At this time, [(18)F]3'-F-PiB (Flutemetamol), (18)F-AV-45 (Florbetapir), and (18)F-AV-1 (Florbetaben) are undergoing extensive phase II and III clinical trials. This article provides a brief review of the amyloid biology and chemistry of A\u03b2-specific (11)C and (18)F-PET radiopharmaceuticals. Clinical trials have clearly documented that PET radiopharmaceuticals capable of assessing A\u03b2 content in vivo in the brains of AD subjects and subjects with mild cognitive impairment will be important as diagnostic agents to detect in vivo amyloid brain pathology. In addition,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21624562", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 1758, "text": "is well known that many clinical and genetic factors have been associated with beta-amyloid deposition, few studies have examined the interactions of such factors across different stages of Alzheimer's pathogenesis. METHODS: We used 18F-florbetapir F18 PET imaging to quantify neuritic beta-amyloid plaque density across four cortical regions in 602 elderly (55-94 years) subjects from the national ADNI biomarker study. The group comprised of 194 normal elderly, 212 early mild cognitive impairment [EMCI], 132 late mild cognitive impairment [LMCI], and 64 mild Alzheimer's (AD). FINDINGS: In a model incorporating multiple predictive factors, the effect of apolipoprotein E \u03b54 and diagnosis was significant on all four cortical regions. The highest signals were seen in cingulate followed by frontal and parietal with lowest signals in temporal lobe (p<0.0001). The effect of apolipoprotein E \u03b54 (Cohen's D 0.96) on beta-amyloid plaque density was approximately twice as large as the effect of a diagnosis of AD (Cohen's D 0.51) and thrice as large as the effect of a diagnosis of LMCI (Cohen's D 0.34) (p<0.0001). Surprisingly, ApoE \u03b54+ normal controls had greater mean plaque density across all cortical regions than \u03b54- EMCI and \u03b54- LMCI (p<0.0001, p=0.0009) and showed higher, though non-significant, mean value than \u03b54- AD patients (p<0.27). ApoE \u03b54+ EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than \u03b54- AD patients (p<0.027, p<0.0001). INTERPRETATION: Neuritic amyloid plaque load across progressive clinical stages of AD varies strongly by ApoE4 genotype. These findings support the need for better pathology-based and supported diagnosis in routine practice. Our data als", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624169", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 1155, "text": "sitron emission tomography (PET) radiotracers, fluorodeoxyglucose F 18 ((18)F-FDG) is the compound most widely used in the diagnosis of neurodegenerative dementias. However, this compound shows a level of specificity and sensitivity for early Alzheimer's disease detection that is lower than that provided by high-affinity ligands for \u03b2-amyloid (A\u03b2). Among the new widely available fluorine 18 ((18)F)-labeled A\u03b2 ligands, florbetapir F 18 ((18))F-AV-45; Amyvid\u2122) showed clear qualitative and quantitative correlations between in vivo PET imaging and postmortem histopathologic analysis of A\u03b2. Florbetapir F 18 stands out for its high A\u03b2 affinity and its pharmacokinetic properties that allow 10-minute PET scan imaging within 90 minutes after administration (dose = 370 MBq). Importantly, no safety concerns for florbetapir F 18 were found in preclinical studies. In 2012, the U.S. Food and Drug Administration (FDA) approved Amyvid as a radiotracer helpful for excluding the presence of A\u03b2 in the brain. It was the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23527322", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 472, "text": " (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD. METHODS: 15 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18191617", "endSection": "abstract" } ] }, { "body": "What was the purpose of the FANTOM3 project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16683036", "http://www.ncbi.nlm.nih.gov/pubmed/20428234", "http://www.ncbi.nlm.nih.gov/pubmed/16381948" ], "ideal_answer": [ " The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species", "Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species." ], "exact_answer": [ "The comprehensive characterization of the mouse transcriptome." ], "type": "factoid", "id": "569e79ecceceede94d000002", "snippets": [ { "offsetInBeginSection": 1558, "offsetInEndSection": 1818, "text": " The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16683036", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1249, "text": "Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1435, "text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 520, "text": "Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428234", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1253, "text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 335, "text": "Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428234", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1357, "text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. Now access is free for all users through the World Wide Web at http://fantom3.gsc.riken.jp/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 323, "text": "Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428234", "endSection": "abstract" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1264, "text": "Their associations and TU attributes are available to find promoters of interest. These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1343, "text": "These databases were provided for Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. Now access is free for all users through the World Wide Web at http://fantom3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381948", "endSection": "abstract" } ] }, { "body": "In which isochores are Alu elements enriched?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8828040", "http://www.ncbi.nlm.nih.gov/pubmed/19543403", "http://www.ncbi.nlm.nih.gov/pubmed/9931467", "http://www.ncbi.nlm.nih.gov/pubmed/15871047", "http://www.ncbi.nlm.nih.gov/pubmed/22057813", "http://www.ncbi.nlm.nih.gov/pubmed/11591470", "http://www.ncbi.nlm.nih.gov/pubmed/6572942", "http://www.ncbi.nlm.nih.gov/pubmed/7723057" ], "ideal_answer": [ "Alu elements are enriched in high GC% isochores due to reduced Alu loss by recombination in these regions. The frequency of Alu sequences increases with increasing GC, but attains a maximum in H2 isochores." ], "exact_answer": [ [ "H2" ], [ "H3" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032085", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020087" ], "type": "list", "id": "515bd543298dcd4e51000001", "snippets": [ { "offsetInBeginSection": 146, "offsetInEndSection": 241, "text": " the vast majority of Alu sequences were shown to have the highest density in GC-rich isochores", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22057813", "endSection": "sections.0" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1103, "text": "Alu sequences being unstable in the GC-poor isochores but stable in the compositionally matching GC-rich isochores,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22057813", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Alu retrotransposons do not show a homogeneous distribution over the human genome but have a higher density in GC-rich (H) than in AT-rich (L) isochores", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15871047", "endSection": "sections.0" }, { "offsetInBeginSection": 1230, "offsetInEndSection": 1463, "text": "This result, together with the known higher selective disadvantage of recombination products in H isochores, points to Alu-Alu recombination as the main agent provoking the density shift of Alus toward the GC-rich parts of the genome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15871047", "endSection": "sections.0" }, { "offsetInBeginSection": 175, "offsetInEndSection": 235, "text": "whereas GC-rich Alus are mostly present in GC-rich isochores", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11591470", "endSection": "sections.0" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1469, "text": "the present results on Alu and LINE stability/exclusion predict significant losses of Alu DNA from the GC-poor isochores during evolution, a phenomenon apparently due to negative selection against sequences that differ from the isochore composition", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11591470", "endSection": "sections.0" }, { "offsetInBeginSection": 780, "offsetInEndSection": 929, "text": "The frequency of Alu sequences also increases with increasing GC, but attains a maximum in H2 isochores, in agreement with previous experimental data", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9931467", "endSection": "sections.0" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1643, "text": "The CpG levels of both Alus and CpG islands increase with their GC levels", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9931467", "endSection": "sections.0" }, { "offsetInBeginSection": 327, "offsetInEndSection": 416, "text": "characterized as a GC-rich isochore enriched for CpG islands, genes, and Alu-like repeats", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8828040", "endSection": "sections.0" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1414, "text": "Microsatellites and SINES (Alu, B1, B2) are found at roughly equal frequencies in introns from all isochore classes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7723057", "endSection": "sections.0" }, { "offsetInBeginSection": 500, "offsetInEndSection": 776, "text": "The results indicate that the short repeats of the B1 family of mouse and of the Alu I family of man are most frequent in the heavy components, whereas the long repeats of the BamHI family of mouse and of the Kpn I family of man are mainly present in the two light components.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6572942", "endSection": "sections.0" } ] }, { "body": "Is oxalate renal excretion increased after bariatric surgery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21295813", "http://www.ncbi.nlm.nih.gov/pubmed/23821183", "http://www.ncbi.nlm.nih.gov/pubmed/16925274", "http://www.ncbi.nlm.nih.gov/pubmed/18701613", "http://www.ncbi.nlm.nih.gov/pubmed/18501812", "http://www.ncbi.nlm.nih.gov/pubmed/9689695", "http://www.ncbi.nlm.nih.gov/pubmed/23024163", "http://www.ncbi.nlm.nih.gov/pubmed/20566568", "http://www.ncbi.nlm.nih.gov/pubmed/19762051", "http://www.ncbi.nlm.nih.gov/pubmed/19013593", "http://www.ncbi.nlm.nih.gov/pubmed/2218396", "http://www.ncbi.nlm.nih.gov/pubmed/16217311", "http://www.ncbi.nlm.nih.gov/pubmed/17222634", "http://www.ncbi.nlm.nih.gov/pubmed/22554593", "http://www.ncbi.nlm.nih.gov/pubmed/2669121" ], "ideal_answer": [ "Bariatric surgery is associated with a significant risk of nephrolithiasis.\nEnteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of bariatric surgery\nHyperoxaluria in patients treated with bariatric surgery was found to be a result of hyperabsorption of oxalate", "Urinary oxalate increases after bariatric surgery" ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007588", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002129", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015390", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010070", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049088", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050110", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013502" ], "type": "yesno", "id": "52df887498d023950500000c", "snippets": [ { "offsetInBeginSection": 280, "offsetInEndSection": 630, "text": "Despite the fact that bariatric surgery-induced weight loss is associated with a significant decrease in morbidity and mortality and improvement in renal function, bariatric surgery has recently been shown to be associated with a significant risk of nephrolithiasis. The main risk factor for nephrolithiasis is increased excretion of urinary oxalate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20566568", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1557, "text": "Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16925274", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 724, "text": "The urinary excretion of oxalate was high: 1.112 mumol/24 h (normal range: 55-400 mumol/24 h), and citrate excretion was low: 1.48 mmol/24 h (normal range: 2-5 mmol/24 h). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9689695", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 981, "text": "Hyperoxaluria in patients with JIB was found to be a result of hyperabsorption of oxalate, and these patients displayed altered oxalate kinetics with continued urinary excretion of orally administered 14C-oxalate for more than 48 hours. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2669121", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1517, "text": "Malabsorption of calcium and low fasting urinary calcium excretion in the JIB patients were associated with high tubular reabsorption of calcium, the latter presumably attributable to a compensatory increase in circulating parathyroid hormone (PTH). In most recurrent renal stone formers the urinary calcium concentration was increased, with an inverse relationship to serum PTH, indicating intestinal hyperabsorption of calcium. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2669121", "endSection": "abstract" } ] }, { "body": "Which are the mutational hotspots of the human KRAS oncogene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23074403", "http://www.ncbi.nlm.nih.gov/pubmed/19430299", "http://www.ncbi.nlm.nih.gov/pubmed/16458330", "http://www.ncbi.nlm.nih.gov/pubmed/22006429", "http://www.ncbi.nlm.nih.gov/pubmed/23536897", "http://www.ncbi.nlm.nih.gov/pubmed/21199003", "http://www.ncbi.nlm.nih.gov/pubmed/11403720", "http://www.ncbi.nlm.nih.gov/pubmed/16434186", "http://www.ncbi.nlm.nih.gov/pubmed/21266528", "http://www.ncbi.nlm.nih.gov/pubmed/12650907", "http://www.ncbi.nlm.nih.gov/pubmed/10768832", "http://www.ncbi.nlm.nih.gov/pubmed/14534542", "http://www.ncbi.nlm.nih.gov/pubmed/12941809", "http://www.ncbi.nlm.nih.gov/pubmed/17638058" ], "ideal_answer": [ "The KRAS oncogene has four main mutational hotspots located at codons 12, 13, 61 and 146.", "The mutational hotspots for the K-ras oncogene are codons 12 and 13" ], "exact_answer": [ [ "Codon 12" ], [ "Codon 13" ], [ "Codon 61" ], [ "Codon 146" ], [ "Codon 18" ], [ "Codon 31" ], [ "Codon 15" ] ], "concepts": [ "http://www.uniprot.org/uniprot/RASK_RAT", "http://www.uniprot.org/uniprot/RASK_ORYLA", "http://www.uniprot.org/uniprot/RASK_MSVKI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017384", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017354", "http://www.uniprot.org/uniprot/RASK_MONDO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054643", "http://www.uniprot.org/uniprot/RASK_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020125", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/RASK_KRYMA", "http://www.uniprot.org/uniprot/RASK_XENLA", "http://www.uniprot.org/uniprot/RASK_CYPCA", "http://www.uniprot.org/uniprot/RASK_HUMAN", "http://www.uniprot.org/uniprot/RASK_MELGA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004252" ], "type": "list", "id": "52e6c92598d0239505000019", "snippets": [ { "offsetInBeginSection": 613, "offsetInEndSection": 726, "text": "In this study we analyzed 15 sMTC for mutations in the hotspots codon 12, 13 and 61 of the H- and K-ras oncogene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10768832", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 891, "text": "mutation in the codon 12, 13 and 61 of the H-ras and K-ras oncogene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10768832", "endSection": "abstract" }, { "offsetInBeginSection": 31, "offsetInEndSection": 155, "text": "the mutation hotspots of the K-ras proto-oncogene in human functional adrenocortical tumors are in codons 15, 16, 18, and 31", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11403720", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 130, "text": "mutations C742T, G746T, G747T in the TP53 gene and G35T in the KRAS gene have been repeatedly found in sectors of human tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16458330", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 293, "text": "exons 1 and 2 of KRAS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21266528", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 329, "text": "KRAS (codon 12/13 hotspot)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199003", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 711, "text": "three hotspots in KRAS (codons 12/13, 61 and 146)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199003", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 791, "text": "analysis of KRAS (codon12/13)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199003", "endSection": "abstract" }, { "offsetInBeginSection": 2359, "offsetInEndSection": 2440, "text": "mutations occurring in mutational hotspots (codons 12 and 13) of the KRAS protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074403", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 539, "text": "and N-, K-, and H-RAS (codons 12, 13, and 61)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17638058", "endSection": "abstract" } ] }, { "body": "Which intraflagellar transport (IFT) motor protein has been linked to human skeletal ciliopathies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "http://www.ncbi.nlm.nih.gov/pubmed/25205765", "http://www.ncbi.nlm.nih.gov/pubmed/25470043", "http://www.ncbi.nlm.nih.gov/pubmed/24183451" ], "ideal_answer": [ "Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies", "Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS)." ], "exact_answer": [ "Intraflagellar transport (IFT) motor protein DYNC2H1" ], "type": "factoid", "id": "57279ef20fd6f91b68000018", "snippets": [ { "offsetInBeginSection": 295, "offsetInEndSection": 411, "text": "Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25470043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 525, "text": "Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 656, "text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 617, "text": "Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 408, "text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 410, "text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 413, "text": "Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25470043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 527, "text": "Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": " Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 525, "text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": " Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies. Here, we define for the first time the composition of the human cytoplasmic dynein-2 complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 527, "text": "The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 410, "text": "All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205765", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 527, "text": "Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183451", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of ocrelizumab for treatment of multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24579720", "http://www.ncbi.nlm.nih.gov/pubmed/23609782", "http://www.ncbi.nlm.nih.gov/pubmed/24494635", "http://www.ncbi.nlm.nih.gov/pubmed/24928997", "http://www.ncbi.nlm.nih.gov/pubmed/24444048", "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "http://www.ncbi.nlm.nih.gov/pubmed/24832354", "http://www.ncbi.nlm.nih.gov/pubmed/18951300", "http://www.ncbi.nlm.nih.gov/pubmed/24090587", "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "http://www.ncbi.nlm.nih.gov/pubmed/22766059", "http://www.ncbi.nlm.nih.gov/pubmed/24251808", "http://www.ncbi.nlm.nih.gov/pubmed/25732947", "http://www.ncbi.nlm.nih.gov/pubmed/24707333", "http://www.ncbi.nlm.nih.gov/pubmed/24032475", "http://www.ncbi.nlm.nih.gov/pubmed/22229582", "http://www.ncbi.nlm.nih.gov/pubmed/22171583", "http://www.ncbi.nlm.nih.gov/pubmed/24001305", "http://www.ncbi.nlm.nih.gov/pubmed/23208729", "http://www.ncbi.nlm.nih.gov/pubmed/25296871" ], "ideal_answer": [ "Ocrelizumab is a cytolytic monoclonal antibody that binds CD20 antigen present of B cells. It is approved for treatment of multiple sclerosis." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103", "http://www.biosemantics.org/jochem#4002285", "http://www.disease-ontology.org/api/metadata/DOID:2377" ], "type": "summary", "id": "56c1f011ef6e394741000042", "snippets": [ { "offsetInBeginSection": 80, "offsetInEndSection": 474, "text": "Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. interferon beta and glatiramer acetate), development of novel anti-neuroinflammatory medications (e.g. fingolimod, teriflunomide and dimethyl fumarate, daclizumab, alemtuzumab, ocrelizumab) and investigation of treatments in progressive MS (e.g. natalizumab, mastinib, natalizumab, siponimod).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24707333", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 772, "text": "This review provides insights into clinical studies with the mAbs natalizumab, alemtuzumab, daclizumab, rituximab, ocrelizumab and ofatumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24001305", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1456, "text": "Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24032475", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 940, "text": "More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24444048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24928997", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 738, "text": "Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25732947", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1538, "text": " To reduce the risk of infusion reactions and improve long-term tolerability, the human-derived components of the antibody have been increased to form humanized or human monoclonal antibodies like ocrelizumab and ofatumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25296871", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1149, "text": "Ocrelizumab will likely also be licensed as a second-line therapy in highly active MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24579720", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 814, "text": "This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251808", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1579, "text": "In this review, we further discuss evidence for B cell and Ig contribution to human MS and NMO pathogenesis, pro-inflammatory and regulatory B cell effector functions, impaired B cell immune tolerance, the B cell-fostering microenvironment in the CNS, and B cell-targeted therapeutic interventions for MS and NMO, including CD20 depletion (rituximab, ocrelizumab, and ofatumumab), anti-IL6-R (tocilizumab), complement-blocking (eculizumab), inhibitors of AQP4-Ig binding (aquaporumab, small molecular compounds), and BAFF/BAFF-R-targeting agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24832354", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 979, "text": "The main efficacy and safety results of these drugs are reviewed in this paper. They can be classified into 2 groups: oral (fingolimod, laquinimod, teriflunomide, BG-12 [dimethyl fumarate], oral cladribine, dalfampridine) and monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22766059", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 883, "text": "Daclizumab and ocrelizumab are monoclonal antibodies that have shown efficacy and acceptable safety profiles in phase 2 trials; both are under investigation in ongoing phase 3 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090587", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 585, "text": " As such, humoral targeted immunotherapies that are being developed for MS are discussed herein: rituximab, ocrelizumab, and ofatumumab show promise as B-cell depleting agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23208729", "endSection": "abstract" }, { "offsetInBeginSection": 889, "offsetInEndSection": 1052, "text": " The section on anti-CD20 antibodies reviews Phase II results on ocrelizumab and ofatumumab, and discusses current perspectives of these antibodies for MS therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "endSection": "abstract" }, { "offsetInBeginSection": 1655, "offsetInEndSection": 1858, "text": "Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23609782", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1439, "text": "In addition, oral laquinimod, several monoclonal antibodies (eg, alemtuzumab, daclizumab, and ocrelizumab), and other agents have shown preliminary beneficial results in relapsing MS in phase 3 clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24494635", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 1010, "text": "They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22171583", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 933, "text": "The second concept is to deplete T cells and/or B cells from the peripheral circulation using highly specific monoclonal antibodies such as alemtuzumab (anti-CD52) or rituximab/ocrelizumab (anti-CD20). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22229582", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1200, "text": "More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24444048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Biogen Idec Inc, Genentech Inc, Roche Holding AG and Chugai Pharmaceutical Co Ltd are developing ocrelizumab, a humanized mAb against CD20, for the potential treatment of inflammatory disorders and B-cell malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18951300", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Ocrelizumab, a humanized monoclonal antibody against CD20 for inflammatory disorders and B-cell malignancies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18951300", "endSection": "title" }, { "offsetInBeginSection": 246, "offsetInEndSection": 421, "text": "We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 260, "text": "We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "endSection": "abstract" } ] }, { "body": "What is the link between Nonidet-40 (NP-40) and biotinylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23500724" ], "ideal_answer": [ "0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins.", "NP-40 reduces contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins." ], "exact_answer": [ "Reduction of contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins." ], "concepts": [ "http://www.biosemantics.org/jochem#4252646" ], "type": "factoid", "id": "56a8d660a17756b72f000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "NP-40 reduces contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724", "endSection": "title" }, { "offsetInBeginSection": 345, "offsetInEndSection": 630, "text": "We show that the use of 0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination of nuclear extracts by carboxylases and to greatly reduce background signals in downstream mass spectrometric analyses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 631, "text": "We describe here a simple procedure for greatly reducing contamination of nuclear extracts by naturally biotinylated cytoplasmic carboxylases, which represent a major source of non-specific background when employing BirA-mediated biotinylation tagging for the purification and characterization of nuclear protein complexes by mass spectrometry. We show that the use of 0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination of nuclear extracts by carboxylases and to greatly reduce background signals in downstream mass spectrometric analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 632, "text": " We describe here a simple procedure for greatly reducing contamination of nuclear extracts by naturally biotinylated cytoplasmic carboxylases, which represent a major source of non-specific background when employing BirA-mediated biotinylation tagging for the purification and characterization of nuclear protein complexes by mass spectrometry. We show that the use of 0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination of nuclear extracts by carboxylases and to greatly reduce background signals in downstream mass spectrometric analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23500724", "endSection": "abstract" } ] }, { "body": "Which is the transcript responsible for X-chromosome inactivation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23847260", "http://www.ncbi.nlm.nih.gov/pubmed/24040022", "http://www.ncbi.nlm.nih.gov/pubmed/21094887", "http://www.ncbi.nlm.nih.gov/pubmed/22065773", "http://www.ncbi.nlm.nih.gov/pubmed/12952890", "http://www.ncbi.nlm.nih.gov/pubmed/21660507", "http://www.ncbi.nlm.nih.gov/pubmed/21471966", "http://www.ncbi.nlm.nih.gov/pubmed/23535403", "http://www.ncbi.nlm.nih.gov/pubmed/16679409", "http://www.ncbi.nlm.nih.gov/pubmed/9678349", "http://www.ncbi.nlm.nih.gov/pubmed/16507360", "http://www.ncbi.nlm.nih.gov/pubmed/9487391", "http://www.ncbi.nlm.nih.gov/pubmed/7536936", "http://www.ncbi.nlm.nih.gov/pubmed/8353487", "http://www.ncbi.nlm.nih.gov/pubmed/9024780", "http://www.ncbi.nlm.nih.gov/pubmed/11751274", "http://www.ncbi.nlm.nih.gov/pubmed/12667455", "http://www.ncbi.nlm.nih.gov/pubmed/22925639", "http://www.ncbi.nlm.nih.gov/pubmed/16107314", "http://www.ncbi.nlm.nih.gov/pubmed/21364561", "http://www.ncbi.nlm.nih.gov/pubmed/21947263", "http://www.ncbi.nlm.nih.gov/pubmed/22889989", "http://www.ncbi.nlm.nih.gov/pubmed/17333537", "http://www.ncbi.nlm.nih.gov/pubmed/23122604", "http://www.ncbi.nlm.nih.gov/pubmed/23166390", "http://www.ncbi.nlm.nih.gov/pubmed/15015744", "http://www.ncbi.nlm.nih.gov/pubmed/9099757", "http://www.ncbi.nlm.nih.gov/pubmed/19013827", "http://www.ncbi.nlm.nih.gov/pubmed/10359800", "http://www.ncbi.nlm.nih.gov/pubmed/9074937", "http://www.ncbi.nlm.nih.gov/pubmed/10026129", "http://www.ncbi.nlm.nih.gov/pubmed/20043281", "http://www.ncbi.nlm.nih.gov/pubmed/21820484", "http://www.ncbi.nlm.nih.gov/pubmed/23093590", "http://www.ncbi.nlm.nih.gov/pubmed/11774371" ], "ideal_answer": [ "The long non- coding RNA Xist (X inactive specific transcript)" ], "exact_answer": [ "Xist" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009048", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049951", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900095", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900096" ], "type": "factoid", "id": "5353aedb288f4dae47000006", "snippets": [ { "offsetInBeginSection": 359, "offsetInEndSection": 419, "text": "Xist, a gene responsible for X chromosome inactivation (XCI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22065773", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1519, "text": "X inactivation-specific transcript (XIST) is a long ncRNA that mediates X chromosome inactivation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21094887", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 329, "text": "the X inactive specific transcript (Xist) gene, which is known now to represent the master switch locus regulating X inactivation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9487391", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 106, "text": "IST, a long non-coding RNA, plays an important role in triggering X chromosome inactivation in eutherians", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040022", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 260, "text": "X inactive-specific transcript (XIST) gene in humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23847260", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 589, "text": "Xist (X-inactive specific transcript) is a major effector of the X-inactivation process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23535403", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 468, "text": "efforts have been focused on the X inactive-specific transcript (Xist) locus, discovered to be the master regulator of X-inactivation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166390", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1069, "text": "X-inactivation specific transcript (Xist) RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122604", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 193, "text": "transcriptional silencing of one of the female X-chromosomes is a finely regulated process that requires accumulation in cis of the long non-coding RNA X-inactive-specific transcript (Xist)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23093590", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 331, "text": "the X-inactivated-specific transcript (Xist) gene, whose gene product consists of RNA which coats and thereby inactivates one of the X chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22925639", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 255, "text": "the X inactivation center (Xic). Xic contains many of the regulatory elements for the mutual interplay of X-inactive specific transcript (Xist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22889989", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 120, "text": "chromosome inactivation (XCI) in female mammals depends on the noncoding RNA X inactivation specific transcript (Xist)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947263", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 371, "text": " One of the striking features that characterize the Xic landscape is the abundance of loci transcribing non-coding RNAs (ncRNAs), including Xist, the master regulator of the inactivation process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21820484", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 352, "text": "The process is mediated by the non-coding RNA X inactive specific transcript (Xist) that binds in cis and propagates along the inactive X chromosome elect, triggering chromosome-wide silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21660507", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 387, "text": "the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21471966", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 642, "text": "X-inactive-specific transcript (Xist) gene ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364561", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 675, "text": "expression of the non-coding X-inactive specific transcript (Xist) RNA and depends on specific cellular contexts, in which essential silencing factors are expressed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20043281", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 432, "text": "Xist (X-inactive specific transcript) and Tsix gene pair, which is pivotal in X-inactivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19013827", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 359, "text": "In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17333537", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 176, "text": " inactivation in female mammals involves transcriptional silencing of an entire chromosome in response to a cis-acting noncoding RNA, the X inactive-specific transcript (Xist)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16679409", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 92, "text": "chromosome inactivation (XCI) depends on a noncoding sense-antisense transcript pair, Xist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16507360", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 217, "text": " The key regulatory molecule that triggers silencing is the Xist transcrip", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16107314", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 216, "text": "chromosome inactivation begins when a novel chromosomal RNA (cRNA) from the imprinted mouse Xist or human XIST locus coats or \"paints\" one X chromosome in cis and initiates a cascade of chromosome remodeling events", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15015744", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 122, "text": "X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12952890", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 220, "text": " In X chromosome inactivation (XCI), unfavorable XCI ratios promote X-linked disease penetrance in females. During XCI, one X is randomly silenced by Xist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12667455", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 121, "text": " imprinted mouse Xist (X-inactive specific transcript) gene is involved in the initiation of X-chromosome inactivation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11774371", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 212, "text": "initiation of X-chromosome inactivation are critically dependent on the expression of the X-inactive specific transcript (Xist)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11751274", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 178, "text": "X chromosome inactivation requires the presence, in cis, of the X inactivation center (XIC). The Xist gene, which lies within the XIC region in both human and mouse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10359800", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 36, "text": "inactive-specific transcript (Xist", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10026129", "endSection": "title" }, { "offsetInBeginSection": 17, "offsetInEndSection": 187, "text": " X inactive-specific transcript (Xist) is thought to be essential for the initiation of X chromosome inactivation and dosage compensation during female embryo development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10026129", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 574, "text": "deletions of the X inactivation center (XIC/Xic) and/or the X inactive specific transcript (XIST/Xist) gene result in failure of cis X-inactivation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9678349", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 100, "text": "Xist (X inactive specific transcript) gene plays an essential role in X chromosome inactivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9099757", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1086, "text": "expression of the Xist (X inactive specific transcript) gene correlates with X inactivation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9074937", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 863, "text": "XIST (X inactive specific transcript) gene ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9024780", "endSection": "abstract" }, { "offsetInBeginSection": 38, "offsetInEndSection": 355, "text": "one of the two X chromosomes in somatic cells of the female becomes inactivated through a process that is thought to depend on a unique initiator region, the X-chromosome inactivation center (Xic). The recently characterized Xist sequence (X-inactive-specific transcript) is thought to be a possible candidate for Xic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7536936", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 73, "text": "human XIST gene, a candidate for a role in X chromosome inactivation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8353487", "endSection": "abstract" } ] }, { "body": "What are viral vectors used for in optogenetics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23283335", "http://www.ncbi.nlm.nih.gov/pubmed/21041318", "http://www.ncbi.nlm.nih.gov/pubmed/25352792", "http://www.ncbi.nlm.nih.gov/pubmed/24647936", "http://www.ncbi.nlm.nih.gov/pubmed/22341326", "http://www.ncbi.nlm.nih.gov/pubmed/23724838", "http://www.ncbi.nlm.nih.gov/pubmed/23217739", "http://www.ncbi.nlm.nih.gov/pubmed/25070340", "http://www.ncbi.nlm.nih.gov/pubmed/23877069", "http://www.ncbi.nlm.nih.gov/pubmed/24572099", "http://www.ncbi.nlm.nih.gov/pubmed/23088961", "http://www.ncbi.nlm.nih.gov/pubmed/25954011", "http://www.ncbi.nlm.nih.gov/pubmed/21278729", "http://www.ncbi.nlm.nih.gov/pubmed/24001071", "http://www.ncbi.nlm.nih.gov/pubmed/23044043", "http://www.ncbi.nlm.nih.gov/pubmed/21373649", "http://www.ncbi.nlm.nih.gov/pubmed/22341319", "http://www.ncbi.nlm.nih.gov/pubmed/22890236", "http://www.ncbi.nlm.nih.gov/pubmed/24285886", "http://www.ncbi.nlm.nih.gov/pubmed/24048849", "http://www.ncbi.nlm.nih.gov/pubmed/25741722", "http://www.ncbi.nlm.nih.gov/pubmed/25759964", "http://www.ncbi.nlm.nih.gov/pubmed/21782903" ], "ideal_answer": [ "Viral vectors are used to express optogenetic constructs in selected cells." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0044009" ], "type": "summary", "id": "56e0813651531f7e33000010", "snippets": [ { "offsetInBeginSection": 1342, "offsetInEndSection": 1580, "text": "To express ChR in neurons, the common expression systems include viral vectors, in utero electroporation, and transgenic animals, each with their advantages and limitations regarding the cost, expression pattern, and the required effort. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22341319", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 744, "text": "In this review, the various strategies for selective genetic targeting of a defined neuronal population are discussed as well as the pros and cons of the use of transgenic animals and recombinant viral vectors for the expression of transgenes in a specific set of neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22341326", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 451, "text": "We demonstrate how the ability to target astrocytes with cell-specific viral vectors to express optogenetic constructs helped to unravel some previously unsuspected roles of these inconspicuous cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21041318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Optogenetics, the use of light to stimulate or inhibit neural circuits via viral transduction of protein channels, has emerged as a possible method of treating epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724838", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 649, "text": "We demonstrate how the ability to target astrocytes with cell-specific viral vectors to express optogenetic constructs helped to unravel some previously unsuspected roles of these inconspicuous cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21041318", "endSection": "abstract" }, { "offsetInBeginSection": 1644, "offsetInEndSection": 1833, "text": "We conclude that a viral vector approach with a strong promoter is required for successful optogenetic stimulation of distal axons to evoke transmitter release in pre-autonomic PVN neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890236", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1169, "text": "RESULTS: Extracellular single-unit recordings were made from infralimbic (IL) pyramidal cells, IL interneurons and prelimbic (PL) pyramidal cells 2-3 weeks after intra-IL injection of a viral vector encoding channel rhodopsin 2 (ChR2) under the control of the CaMKII promoter (rAAV5/CaMKIIa-ChR2(H134R)-EYFP) or a control vector that lacked the ChR2 sequence (rAAV5/CaMKIIa-EYFP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044043", "endSection": "abstract" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1651, "text": "We conclude that a viral vector approach with a strong promoter is required for successful optogenetic stimulation of distal axons to evoke transmitter release in pre-autonomic PVN neurons. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890236", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 756, "text": "We selectively expressed ChR2(H134R) in rostral VLM catecholaminergic neurons by injecting Cre-dependent adeno-associated viral vectors into the brain of adult dopamine-\u03b2-hydroxylase (D\u03b2H)(Cre/0) mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285886", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 848, "text": "We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25741722", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 695, "text": "We generated rabies glycoprotein-pseudotyped lentiviral vectors that use a positive feedback loop composed of a Tet promoter driving both its own tetracycline-dependent transcription activator (tTA) (\"TLoop\") and channelrhodopsin-2-YFP (ChR2YFP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24572099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Optogenetic control of cardiomyocytes via viral delivery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25070340", "endSection": "title" }, { "offsetInBeginSection": 350, "offsetInEndSection": 577, "text": "Here, we used an optogenetic approach, in which female rats received bilateral dorsal mPFC microinjections of viral constructs coding light-sensitive eNpHR3.0-eYFP or control eYFP protein and intracranial fiber optic implants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23283335", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 417, "text": "We transduced rat LC neurons by direct injection of a lentiviral vector expressing channelrhodopsin2 under the control of the PRS promoter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24647936", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 321, "text": "Here, we describe the construction of a blue-light-induced K(+) channel 1 (BLINK1) engineered by fusing the plant LOV2-J\ufffd photosensory module to the small viral K(+) channel Kcv. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25954011", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 908, "text": "In parallel, remarkable success in the development of highly efficient viral vectors for ocular gene therapy led to new strategies of using these novel optogenetic tools for vision restoration. These recent findings show that novel optogenetic tools and viral vectors for ocular gene delivery are now available providing many opportunities to develop potential optogenetic strategies for vision restoration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759964", "endSection": "abstract" } ] }, { "body": "Which domain allowing self-association do exist in TDP-43 and FUS proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24842888", "http://www.ncbi.nlm.nih.gov/pubmed/20356930", "http://www.ncbi.nlm.nih.gov/pubmed/10521526", "http://www.ncbi.nlm.nih.gov/pubmed/22454397", "http://www.ncbi.nlm.nih.gov/pubmed/22065782", "http://www.ncbi.nlm.nih.gov/pubmed/23629963", "http://www.ncbi.nlm.nih.gov/pubmed/24920338", "http://www.ncbi.nlm.nih.gov/pubmed/21327870", "http://www.ncbi.nlm.nih.gov/pubmed/25002999", "http://www.ncbi.nlm.nih.gov/pubmed/22445064", "http://www.ncbi.nlm.nih.gov/pubmed/24262168", "http://www.ncbi.nlm.nih.gov/pubmed/21844169", "http://www.ncbi.nlm.nih.gov/pubmed/22563080", "http://www.ncbi.nlm.nih.gov/pubmed/20720006" ], "ideal_answer": [ "PRION PROTEINS", "Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems. TDP-43, FUS and TAF15 share similar properties, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila. For TDP-43, both the RRM1 and the C-terminal glycine-rich domain are required for SG localization. Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion protein", "Scouring the human genome with this algorithm enriches a select group of RNA-binding proteins harboring a canonical RNA recognition motif (RRM) and a putative prion domain. Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins. PrLDs are over-represented in human RNA-binding proteins and mediate phase transitions underpinning RNP granule assembly. For example, TDP-43 and FUS form cytoplasmic inclusions in amyotrophic lateral sclerosis (ALS) and mutations in TDP-43 and FUS can cause ALS.", "Two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins." ], "exact_answer": [ "Prion-like domain" ], "concepts": [ "http://www.uniprot.org/uniprot/FUS_MOUSE", "http://www.uniprot.org/uniprot/TADBP_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054730", "http://www.uniprot.org/uniprot/TADBP_XENTR", "http://www.uniprot.org/uniprot/FUS_HUMAN", "http://www.uniprot.org/uniprot/TADBP_MOUSE", "http://www.uniprot.org/uniprot/TADBP_HUMAN", "http://www.uniprot.org/uniprot/TADBP_PONAB", "http://www.uniprot.org/uniprot/FUS_BOVIN", "http://amigo.geneontology.org/amigo/term/GO:0043621" ], "type": "factoid", "id": "56c83f365795f9a73e000011", "snippets": [ { "offsetInBeginSection": 288, "offsetInEndSection": 873, "text": "Using transient expression of a panel of deletion and chimeric FUS variants in various cultured cells, we demonstrated that FUS accumulating in the cytoplasm nucleates a novel type of RNA granules, FUS granules (FGs), that are structurally similar but not identical to physiological RNA transport granules. Formation of FGs requires FUS N-terminal prion-like domain and the ability to bind specific RNAs. Clustering of FGs coupled with further recruitment of RNA and proteins produce larger structures, FUS aggregates (FAs), that resemble but are clearly distinct from stress granules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24842888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 620, "text": "Approximately 1% of human proteins harbor a prion-like domain (PrLD) of similar low complexity sequence and amino acid composition to domains that drive prionogenesis of yeast proteins like Sup35. PrLDs are over-represented in human RNA-binding proteins and mediate phase transitions underpinning RNP granule assembly. This modality renders PrLDs prone to misfold into conformers that accrue in pathological inclusions that characterize various fatal neurodegenerative diseases. For example, TDP-43 and FUS form cytoplasmic inclusions in amyotrophic lateral sclerosis (ALS) and mutations in TDP-43 and FUS can cause ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25002999", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1534, "text": "FUS and TDP-43, which rank 1st and 10th among RRM-bearing prion candidates, form cytoplasmic inclusions in the degenerating motor neurons of ALS patients and mutations in TDP-43 and FUS cause familial ALS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22065782", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 790, "text": "two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20356930", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 411, "text": "Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454397", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 789, "text": "Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20356930", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 440, "text": "TDP-43 and FUS and several related RNA-binding proteins harbor aggregation-promoting prion-like domains that allow them to rapidly self-associate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23629963", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 705, "text": "Molecular cloning of subunit 4 of the complex revealed that it is a proteasome-COP9 complex-eIF3 domain protein encoded by a gene that maps to chromosome 5, near the chromosomal location of the cop8 and fus4 mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10521526", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1328, "text": "Deletions in the C-terminal domain of TDP-43 that preclude interactions with hnRNP A2/B1 abolish TDP-43-dependent rescue of CGG repeat toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920338", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 897, "text": "The rescue appears specific to TDP-43, as co-expression of another ALS-associated RNA-binding protein, FUS, exacerbates the toxic effects of CGG repeats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920338", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 455, "text": "Recently, through Next-Generation Exome sequencing approaches a mutation resulting in a substitution (p.Q290X) in the nuclear export domain of the FUS protein was nominated as a cause of autosomal dominant essential tremor (ET) in a large kindred", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24262168", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 602, "text": "TDP-43 is another RNA-binding protein implicated in ALS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24262168", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1183, "text": "We also provide multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454397", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 974, "text": "For TDP-43, both the RRM1 and the C-terminal glycine-rich domain are required for SG localization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22563080", "endSection": "abstract" }, { "offsetInBeginSection": 1628, "offsetInEndSection": 1733, "text": "Furthermore, TDP-43 and FUS display distinct domain requirements in aggregate formation and cytotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21327870", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 878, "text": "Binding was mediated by an unstructured TDP-43 C-terminal domain and occurred within the context of a 300-400-kDa complex that also contained C-terminal cleavage products of TDP-43 linked to neuropathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720006", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 330, "text": "It was recently found that dominant mutations in two related RNA-binding proteins, TDP-43 (43-kDa TAR DNA-binding domain protein) and FUS/TLS (fused in sarcoma/translated in liposarcoma) cause a subset of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720006", "endSection": "abstract" } ] }, { "body": "Is there a role for transcription factories in genome organization?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24003126", "http://www.ncbi.nlm.nih.gov/pubmed/24166911", "http://www.ncbi.nlm.nih.gov/pubmed/16500976", "http://www.ncbi.nlm.nih.gov/pubmed/21880598", "http://www.ncbi.nlm.nih.gov/pubmed/19506577", "http://www.ncbi.nlm.nih.gov/pubmed/17913488", "http://www.ncbi.nlm.nih.gov/pubmed/20074071" ], "ideal_answer": [ "The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer ", "Yes. The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. Those active chromatin hubs and transcription factories also involve long-range interactions. Thus, it seems that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs." ], "exact_answer": "yes", "type": "yesno", "id": "5545dc7de233d84047000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 777, "text": "The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24166911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "In the eukaryotic nucleus, genes are transcribed in transcription factories", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880598", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 756, "text": "Based on this analysis, we propose that transcription factories result from the aggregation of RNA polymerase II-containing pre-initiation complexes assembled next to each other in the nuclear space. Such an aggregation can be triggered by the phosphorylation of the C-terminal domain of RNA polymerase II molecules and their interaction with various transcription factors. Individual transcription factories would thus incorporate tissue-specific, co-regulated as well as housekeeping genes based only on their initial proximity to each other in the nuclear space", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880598", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 794, "text": "active polymerases cluster into replication and transcription \"factories\" in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16500976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Since the advent of FISH (fluorescence in situ hybridization), there have been major advances in our understanding of how the genome is organized in interphase nuclei. Indeed, this organization is found to be non-random and individual chromosomes occupy discrete regions known as territories", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074071", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 663, "text": " in proliferating cells, there is evidently a correlation between radial positioning and gene density. Indeed, gene-poor chromosomes tend to be located towards the nuclear edge, while those that are more gene-rich are positioned more internally", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074071", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 593, "text": "Recently described active chromatin hubs and transcription factories also involve long-range interactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17913488", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 825, "text": "The transcription factory model has implications for the regulation of transcription initiation and elongation, for the organization of genes in the genome, for the co-regulation of genes and for genome instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19506577", "endSection": "abstract" } ] }, { "body": "Which are the Chompret criteria for Li-Fraumeni syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22170717", "http://www.ncbi.nlm.nih.gov/pubmed/19204208" ], "ideal_answer": [ "1) According to the Chompret criteria for LFS, any patient with adrenocortical cancer (ACC), irrespective of age and family history, is at high risk for a TP53 germline mutation.\n2) All families with a p53 mutation must have at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC)." ], "exact_answer": [ [ "Any patient with adrenocortical cancer (ACC), irrespective of age and family history." ], [ "All families with a p53 mutation must have at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC)." ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3948", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012516", "http://www.disease-ontology.org/api/metadata/DOID:3012", "http://www.disease-ontology.org/api/metadata/DOID:3347", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012509", "http://www.disease-ontology.org/api/metadata/DOID:1319", "http://www.disease-ontology.org/api/metadata/DOID:1240", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016864", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007938", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018268" ], "type": "list", "id": "531778ddb166e2b80600000f", "snippets": [ { "offsetInBeginSection": 116, "offsetInEndSection": 292, "text": "According to the Chompret criteria for LFS, any patient with adrenocortical cancer (ACC), irrespective of age and family history, is at high risk for a TP53 germline mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22170717", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 854, "text": "All families with a p53 mutation had at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19204208", "endSection": "abstract" } ] }, { "body": "When ceritinib used instead of crizotinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "http://www.ncbi.nlm.nih.gov/pubmed/24891360", "http://www.ncbi.nlm.nih.gov/pubmed/25945060", "http://www.ncbi.nlm.nih.gov/pubmed/25101329", "http://www.ncbi.nlm.nih.gov/pubmed/26366094", "http://www.ncbi.nlm.nih.gov/pubmed/24856155", "http://www.ncbi.nlm.nih.gov/pubmed/24670165", "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "http://www.ncbi.nlm.nih.gov/pubmed/25258420" ], "ideal_answer": [ "Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC patients that are crizotinib-resistant and crizotinib-na\u00efve." ], "exact_answer": [ [ "crizotinib-resistant ALK-positive metastatic NSCLC patients" ], [ "crizotinib-na\u00efve ALK-positive metastatic NSCLC patients" ] ], "type": "list", "id": "56d042ae3975bb303a00000d", "snippets": [ { "offsetInBeginSection": 840, "offsetInEndSection": 1010, "text": "Ceritinib is a second-generation ALK inhibitor that has demonstrated activity in crizotinib-resistant patients, becoming a promising treatment option in this population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25945060", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 583, "text": "Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC in patients who are intolerant to or have progressed despite therapy with crizotinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258420", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1547, "text": "Ceritinib has activity in crizotinib-resistant and crizotinib-na\u00efve patients and appears to be a viable alternative for ALK-positive NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258420", "endSection": "abstract" }, { "offsetInBeginSection": 1312, "offsetInEndSection": 1985, "text": "In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1415, "text": "Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1191, "text": "Preclinical data showed impressive antitumor activity against crizotinib-resistant clones, and based on available data, ceritinib could represent a suitable option in crizotinib-resistant NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25101329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Ceritinib (LDK378): a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "endSection": "title" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1611, "text": "However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.SIGNIFICANCE: The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib. These findings provide the molecular basis for the marked clinical activity of ceritinib in patients with ALK-positive NSCLC with crizotinib-resistant disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1221, "text": "However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1427, "text": "Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease. The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 1316, "text": "The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1587, "text": "The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib. These findings provide the molecular basis for the marked clinical activity of ceritinib in patients with ALK-positive NSCLC with crizotinib-resistant disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 1348, "text": "In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented. Copyright \u00a9 2015 Elsevier Inc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "endSection": "abstract" } ] }, { "body": "What type of enzyme is peroxiredoxin 2 (PRDX2)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12943237", "http://www.ncbi.nlm.nih.gov/pubmed/17522089", "http://www.ncbi.nlm.nih.gov/pubmed/18479207", "http://www.ncbi.nlm.nih.gov/pubmed/22989627", "http://www.ncbi.nlm.nih.gov/pubmed/19969073", "http://www.ncbi.nlm.nih.gov/pubmed/21248284", "http://www.ncbi.nlm.nih.gov/pubmed/21902453", "http://www.ncbi.nlm.nih.gov/pubmed/20646000", "http://www.ncbi.nlm.nih.gov/pubmed/23889121", "http://www.ncbi.nlm.nih.gov/pubmed/23749642", "http://www.ncbi.nlm.nih.gov/pubmed/21083423", "http://www.ncbi.nlm.nih.gov/pubmed/18222042", "http://www.ncbi.nlm.nih.gov/pubmed/22916248", "http://www.ncbi.nlm.nih.gov/pubmed/19812325", "http://www.ncbi.nlm.nih.gov/pubmed/17105810", "http://www.ncbi.nlm.nih.gov/pubmed/19375361" ], "ideal_answer": [ "Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme that uses cysteine residues to decompose peroxides. \nPeroxiredoxin-2 (PRDX2), an enzyme reducing hydrogen peroxide and lipid peroxides \nPeroxiredoxin 2 (Prx2) is a thiol-dependent peroxidase." ], "exact_answer": [ "antioxidant" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054464" ], "type": "factoid", "id": "52bf1f1303868f1b06000014", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 108, "text": "Peroxiredoxin-2 (PRDX-2) is an antioxidant and chaperone-like protein critical for cell function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23889121", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 349, "text": "We found that the antioxidant enzyme peroxiredoxin-2 (Prx2) inversely correlated with the metastatic capacity of human melanoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23749642", "endSection": "abstract" }, { "offsetInBeginSection": 51, "offsetInEndSection": 248, "text": "The aim of this study was to examine gonadotropin regulation of antioxidant enzyme sulfiredoxin (Srx) and peroxiredoxin 2 (PRDX2) expressions and modification during the ovulatory process in rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22989627", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1392, "text": "The mRNA profiler array showed more than 2-fold differential expression of 32 oxidative stress-related genes in unstimulated moDCs, including peroxiredoxin-2 (PRDX2), an enzyme reducing hydrogen peroxide and lipid peroxides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22916248", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 254, "text": "Peroxiredoxin-2 (Prx-2) is an abundant mammalian enzyme that protects against oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21902453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Peroxiredoxin 2 (PRDX2) has been known to act as an antioxidant enzyme whose main function is H(2)O(2) reduction in cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21248284", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1347, "text": "These data indicate that Srx1 activity protects mice from the lethality of endotoxic shock, adding this enzyme to other host factors, as NRF2 and peroxiredoxin 2, which by regulating cellular reactive oxygen species levels act as important modifiers in the pathogenesis of sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21083423", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 722, "text": "One of the identified proteins was peroxiredoxin 2 (Prx2), an anti-oxidant enzyme. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20646000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Peroxiredoxin-2 (Prdx2), a potent peroxide reductant, is the third most abundant protein in the erythrocyte and might be expected to play a major role in the cell's oxidative defenses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19969073", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 940, "text": "Importantly, we also demonstrate the antioxidant enzyme Prx2 (peroxiredoxin 2) as a critical cytoplasmic target of cdk5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Human erythrocyte peroxiredoxin 2 (Prx2) is a typical 2-cys cytosolic peroxiredoxin with thiol-dependent hydrogen peroxide scavenger activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19375361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Peroxiredoxin 2 (Prx2) is an antioxidant enzyme that uses cysteine residues to decompose peroxides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18479207", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1077, "text": "Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, was the most upregulated while tribbles homolog 3 (TRB3), a pro-apoptotic protein, was the most downregulated, implying a beneficial effect of lithium on neuronal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18222042", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 352, "text": "After 5 Gy irradiation, the relative abundance of peroxiredoxin 2, an antioxidant enzyme, and latexin, an inhibitor of carboxypeptidase, increased. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17522089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Peroxiredoxin 2 (Prx2), a thiol-dependent peroxidase, is the third most abundant protein in the erythrocyte, and its absence in knock-out mice gives rise to hemolytic anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17105810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Suppression subtractive hybridization performed on Down syndrome (DS) versus control fetal brains revealed differential expression of peroxiredoxin 2 (PRDX2), mapped at 13q12. Peroxiredoxins are antioxidant enzymes involved in protein and lipid protection against oxidative injury and in cellular signalling pathways regulating apoptosis. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12943237", "endSection": "abstract" } ] }, { "body": "Is the length of the poly(A) tail involved in human disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20970105" ], "ideal_answer": [ "Yes. Severely truncated poly(A) tails of mitochondrial mRNAs were found to be involved in an autosomal recessive spastic ataxia with optic atrophy." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000289", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026723", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060212", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060213", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060211", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012333" ], "type": "yesno", "id": "52f20d802059c6d71c00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 518, "text": "In human mitochondria, polyadenylation of mRNA, undertaken by the nuclear-encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression. Our molecular investigation of an autosomal-recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype. When subjected to poly(A) tail-length assays, mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20970105", "endSection": "abstract" } ] }, { "body": "Why graphics processing units (GPU) are more suitable for biological tasks than central processing units (CPU)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23391255", "http://www.ncbi.nlm.nih.gov/pubmed/22759575", "http://www.ncbi.nlm.nih.gov/pubmed/18061402", "http://www.ncbi.nlm.nih.gov/pubmed/20715052", "http://www.ncbi.nlm.nih.gov/pubmed/18070356", "http://www.ncbi.nlm.nih.gov/pubmed/22537298", "http://www.ncbi.nlm.nih.gov/pubmed/21357575", "http://www.ncbi.nlm.nih.gov/pubmed/22149859", "http://www.ncbi.nlm.nih.gov/pubmed/23281733", "http://www.ncbi.nlm.nih.gov/pubmed/20589122", "http://www.ncbi.nlm.nih.gov/pubmed/20357844" ], "ideal_answer": [ "Traditional central processing unist (CPUs) are reaching their limit in processing power and are not designed primarily for multithreaded applications. Graphics processing units (GPUs) on the other hand are affordable, scalable computer powerhouses that, thanks to the ever increasing demand for higher quality graphics, have yet to reach their limit. Typically high-end CPUs have 8-16 cores, whereas GPUs can have more than 2,500 cores. GPUs are also, by design, highly parallel, multicore and multithreaded, able of handling thousands of threads doing the same calculation on different subsets of a large data set. This ability is what makes them perfectly suited for biological analysis tasks. Lately this potential has been realized by many bioinformatics researches and a huge variety of tools and algorithms have been ported to GPUs, or designed from the ground up to maximize the usage \nof available cores." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003196" ], "type": "summary", "id": "53355714d6d3ac6a34000045", "snippets": [ { "offsetInBeginSection": 759, "offsetInEndSection": 995, "text": "The global speedups of 22.11, 38.80, and 44.80 are found comparing the parallel computation of one GPU, two GPUs by exact rotational operator, and two GPU versions by an approximate rotational operator with serial computation of the CPU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391255", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 195, "text": "evaluate the use of general-purpose graphics processing units (GPGPUs) to improve the performance of MODFLOW, an unstructured preconditioned conjugate gradient (UPCG) solver has been developed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281733", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 541, "text": "UPCG solver uses a compressed sparse row storage scheme and includes Jacobi, zero fill-in incomplete, and modified-incomplete lower-upper (LU) factorization, and generalized least-squares polynomial preconditioners. The UPCG solver also includes options for sequential and parallel solution on the central processing unit (CPU) using OpenMP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281733", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1544, "text": "Testing indicates GPGPU speedups on the order of 2 to 8, relative to the standard MODFLOW preconditioned conjugate gradient (PCG) solver, can be achieved when (1) memory copies between the CPU and GPGPU are optimized, (2) the percentage of time performing memory copies between the CPU and GPGPU is small relative to the calculation time, (3) high-performance GPGPU cards are utilized, and (4) CPU-GPGPU combinations are used to execute sequential operations that are difficult to parallelize", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281733", "endSection": "abstract" }, { "offsetInBeginSection": 2052, "offsetInEndSection": 2305, "text": "A list-mode ToF OSEM library was developed on the GPU-CUDA platform. Our studies show that the GPU reformulation is considerably faster than a single-threaded reference CPU method especially for ToF processing, while producing virtually identical images", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22149859", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1420, "text": "When applied to line projection operations for non-ToF list-mode PET, this new GPU-CUDA method is >200 times faster than a single-threaded reference CPU implementation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22149859", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 841, "text": "The GPU-based parallel implementation of the Gillespie stochastic simulation algorithm (SSA), the logarithmic direct method (LDM) and the next reaction method (NRM) is approximately 85 times faster than the sequential implementation of the NRM on a central processing unit (CPU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21357575", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 296, "text": "exploration of fundamental biological processes involving the forced unraveling of multimeric proteins, the sliding motion in protein fibers and the mechanical deformation of biomolecular assemblies under physiological force loads is challenging even for distributed computing systems", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20715052", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 692, "text": "We assessed the computational performance of an end-to-end application of the program, where all the steps of the algorithm are running on a GPU, by profiling the simulation time and memory usage for a number of test systems", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20715052", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 847, "text": "Our results show that the GPGPUs can provide significant speedup over conventional processors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20357844", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 207, "text": "explore the power and feasibility of using programmable graphics processing units (GPUs) for real-time rendering and displaying large 3D medical datasets for stereoscopic display workstation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18061402", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 691, "text": "The performance of rendering and displaying was measured and compared between GPU-based and central processing unit (CPU)-based programming. The results indicate that GPU-based programming was capable of rendering large 3D datasets at real-time interactive rates with stereographic displays", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18061402", "endSection": "abstract" } ] }, { "body": "Which are the thyroid hormone analogs utilized in human studies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "http://www.ncbi.nlm.nih.gov/pubmed/20187783", "http://www.ncbi.nlm.nih.gov/pubmed/22947347", "http://www.ncbi.nlm.nih.gov/pubmed/7608251", "http://www.ncbi.nlm.nih.gov/pubmed/18080776", "http://www.ncbi.nlm.nih.gov/pubmed/16384862", "http://www.ncbi.nlm.nih.gov/pubmed/19903697", "http://www.ncbi.nlm.nih.gov/pubmed/23970761", "http://www.ncbi.nlm.nih.gov/pubmed/1193013", "http://www.ncbi.nlm.nih.gov/pubmed/23307789", "http://www.ncbi.nlm.nih.gov/pubmed/22123068", "http://www.ncbi.nlm.nih.gov/pubmed/3730832", "http://www.ncbi.nlm.nih.gov/pubmed/9001190", "http://www.ncbi.nlm.nih.gov/pubmed/23298477", "http://www.ncbi.nlm.nih.gov/pubmed/18386142", "http://www.ncbi.nlm.nih.gov/pubmed/23565368", "http://www.ncbi.nlm.nih.gov/pubmed/21896621" ], "ideal_answer": [ "TRIAC and TETRAC are two different thyroid hormone analogs utilized in human studies" ], "exact_answer": [ [ "TRIAC", "TETRAC" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013956", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006730", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011455" ], "type": "list", "id": "52fb42752059c6d71c00005e", "snippets": [ { "offsetInBeginSection": 273, "offsetInEndSection": 427, "text": "Here, we evaluate the therapeutic potential of the TH analog 3,5,3',5'-tetraiodothyroacetic acid (tetrac) as a replacement for T(4) in brain development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23307789", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1296, "text": "This treatment was sufficient to promote TH-dependent neuronal differentiation in the cerebellum, cerebral cortex, and striatum but was ineffective in suppressing hypothalamic TRH expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23307789", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 620, "text": "In the current study, we investigated the effect of a natural thyroid hormone analogue - 3, 3?, 5-triiodo-thyroacetic acid (TRIAC) on regulating proliferation and differentiation and its possible molecular mechanism in normal human epidermal keratinocytes and C57BL/6 mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298477", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1369, "text": "TRIAC was effective and safe in ameliorating the effects of hyperthyroidism and ADHD symptoms in a child with known genetic RTH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22947347", "endSection": "abstract" } ] }, { "body": "Are patients with marfan syndrome at increased risk of arrhythmias?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17597390", "http://www.ncbi.nlm.nih.gov/pubmed/22738784", "http://www.ncbi.nlm.nih.gov/pubmed/12535830" ], "ideal_answer": [ "Patients with marfan syndrome carry increased risk for arrhythmias" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001145", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306" ], "type": "yesno", "id": "532f0c4ed6d3ac6a3400002e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 183, "text": "Marfan syndrome (MFS) is a variable, autosomal-dominant disorder of the connective tissue. In MFS serious ventricular arrhythmias and sudden cardiac death (SCD) can occur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22738784", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 191, "text": "Marfan's patients carry increased risk for cardiac arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17597390", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 935, "text": "Ventricular arrhythmias were present in 21% and were associated with increased left ventricular size, mitral valve prolapse, and abnormalities of repolarization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12535830", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1277, "text": "Cardiac complications are rare in young patients with Marfan syndrome receiving medical therapy and close clinical follow-up. Sudden death still occurs, and appears more common in patients with a dilated left ventricle. Left ventricular dilation may predispose to alterations of repolarization and fatal ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12535830", "endSection": "abstract" } ] }, { "body": "What are the treatments of choice for GIST (gastrointestinal stromal tumor)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16857109", "http://www.ncbi.nlm.nih.gov/pubmed/19097381", "http://www.ncbi.nlm.nih.gov/pubmed/18958964", "http://www.ncbi.nlm.nih.gov/pubmed/15508453", "http://www.ncbi.nlm.nih.gov/pubmed/16739060", "http://www.ncbi.nlm.nih.gov/pubmed/15655606", "http://www.ncbi.nlm.nih.gov/pubmed/12394270", "http://www.ncbi.nlm.nih.gov/pubmed/17954092", "http://www.ncbi.nlm.nih.gov/pubmed/15672765", "http://www.ncbi.nlm.nih.gov/pubmed/17643218", "http://www.ncbi.nlm.nih.gov/pubmed/15221987", "http://www.ncbi.nlm.nih.gov/pubmed/17229322", "http://www.ncbi.nlm.nih.gov/pubmed/16136600", "http://www.ncbi.nlm.nih.gov/pubmed/15245670", "http://www.ncbi.nlm.nih.gov/pubmed/16566359", "http://www.ncbi.nlm.nih.gov/pubmed/11126742", "http://www.ncbi.nlm.nih.gov/pubmed/18082353", "http://www.ncbi.nlm.nih.gov/pubmed/16437936", "http://www.ncbi.nlm.nih.gov/pubmed/17470686", "http://www.ncbi.nlm.nih.gov/pubmed/14753595", "http://www.ncbi.nlm.nih.gov/pubmed/19829995", "http://www.ncbi.nlm.nih.gov/pubmed/19343179", "http://www.ncbi.nlm.nih.gov/pubmed/16821517", "http://www.ncbi.nlm.nih.gov/pubmed/22678007", "http://www.ncbi.nlm.nih.gov/pubmed/18180842", "http://www.ncbi.nlm.nih.gov/pubmed/15993051", "http://www.ncbi.nlm.nih.gov/pubmed/24325620" ], "ideal_answer": [ "The surgical resection is a treatment of choice for gastrointestinal stromal tumors. It has been shown that adequate surgical resection correlates with high 5-years survival rates for patients with gastric GIST. When they are localized, the treatment of choice is surgical excision, but advanced tumors have a limited response to chemo or radiotherapy. Imatinib (STI571 or Glivec) is a selective inhibitor or tyrosine kinase proteins that has been used successfully in the treatment of advanced GIST. ", "Approximately 80% of patients with metastatic GIST benefit from imatinib, although acquired resistance to the agent may develop. For patients with primary GIST, surgery remains the treatment of choice, and whether outcome is improved by adjuvant imatinib is currently under broad investigation." ], "type": "summary", "id": "5509b6d22e93f0133a000005", "snippets": [ { "offsetInBeginSection": 178, "offsetInEndSection": 258, "text": "Traditionally, the treatment of choice for primary disease is surgical resection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325620", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 524, "text": "no single surgeon or institution gets extensive exposure to these patients so appropriate decision-making is difficult, particularly since the introduction of the tyrosine kinase inhibitor imatinib, which has become an important additional management tool", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325620", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1686, "text": "Surgery aiming at an R0 resection remains the mainstay of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325620", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 170, "text": "The treatment of choice for GIST is surgical resection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22678007", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1422, "text": "Extra luminal colonic gastrointestinal stromal tumors are very rare and can present as mass abdomen. Resection is the treatment of choice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19829995", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 99, "text": "Surgery remains the only curative treatment for gastrointestinal stromal tumour (GIST).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19343179", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 375, "text": "When they are localized, the treatment of choice is surgical excision, but advanced tumors have a limited response to chemo or radiotherapy. Imatinib (STI571 or Glivec) is a selective inhibitor or tyrosine kinase proteins that has been used successfully in the treatment of advanced GIST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18180842", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 717, "text": "Therefore Imatinib can be a therapeutic alternative in patients with metastatic GIST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18180842", "endSection": "abstract" }, { "offsetInBeginSection": 1550, "offsetInEndSection": 1761, "text": "The surgical resection is a treatment of choice for gastrointestinal stromal tumors. It has been shown that adequate surgical resection correlates with high 5-years survival rates for patients with gastric GIST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19097381", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 737, "text": "Approximately 80% of patients with metastatic GIST benefit from imatinib, although acquired resistance to the agent may develop. For patients with primary GIST, surgery remains the treatment of choice, and whether outcome is improved by adjuvant imatinib is currently under broad investigation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16136600", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 873, "text": "combination of imatinib therapy and surgery also may be effective in a subset of patients with metastatic or unresectable primary GIST", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16136600", "endSection": "abstract" } ] }, { "body": "List Kartagener Syndrome Triad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25207108", "http://www.ncbi.nlm.nih.gov/pubmed/19529061", "http://www.ncbi.nlm.nih.gov/pubmed/6984375", "http://www.ncbi.nlm.nih.gov/pubmed/17725169", "http://www.ncbi.nlm.nih.gov/pubmed/16940490", "http://www.ncbi.nlm.nih.gov/pubmed/24019633", "http://www.ncbi.nlm.nih.gov/pubmed/24730627", "http://www.ncbi.nlm.nih.gov/pubmed/20550487", "http://www.ncbi.nlm.nih.gov/pubmed/15025618", "http://www.ncbi.nlm.nih.gov/pubmed/22966723", "http://www.ncbi.nlm.nih.gov/pubmed/17408950", "http://www.ncbi.nlm.nih.gov/pubmed/8290523", "http://www.ncbi.nlm.nih.gov/pubmed/313731", "http://www.ncbi.nlm.nih.gov/pubmed/8080604", "http://www.ncbi.nlm.nih.gov/pubmed/14551758", "http://www.ncbi.nlm.nih.gov/pubmed/9927835", "http://www.ncbi.nlm.nih.gov/pubmed/9018261" ], "ideal_answer": [ "The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome." ], "exact_answer": [ [ "situs inversus" ], [ "bronchiectasis" ], [ "sinusitis" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007619" ], "type": "list", "id": "56be0e4aef6e394741000008", "snippets": [ { "offsetInBeginSection": 414, "offsetInEndSection": 505, "text": "The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24730627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "BACKGROUND: KARTAGENER SYNDROME (KS) IS A RARE CONGENITAL DISEASE CHARACTERISED BY A CLINICAL TRIAD OF SYMPTOMS: situs inversus, chronic rhinosinusitis, and bronchiectasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25207108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Kartagener's syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24019633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "We present a case of a patient with clinically definite ALS, who had earlier suffered from Kartagener syndrome, which is characterized by the triad comprising chronic sinusitis, bronchiectasis, and situs inversus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20550487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Kartagener syndrome (KS), an autosomal recessively inherited disease, is characterized by the triad of situs inversus, bronchiectasis and sinusitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940490", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 459, "text": "In 1933, Manes Kartagener, a Zurich pulmonary physician, reported four patients with the triad of sinusitis, bronchiectasis, and situs inversus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14551758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "A case of a nine year and eight months old child with Kartagener's syndrome (triad) is described: chronic maxillary sinusitis, bronchiectasis and \"situs inversus totalis\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/313731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Kartagener's syndrome is an inherited disease characterized by a triad of symptoms--bronchiectasis, situs inversus and sinusitis--and is classified as an immotile cilia syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9927835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Kartagener's syndrome is characterized by the clinical triad of bronchitis, sinusitis, and situs inversus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9018261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Kartagener's syndrome is a well known classical triad of presentations consisting of bronchiectasis, sinusitis and situs inversus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8080604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Kartagener's syndrome is a rare disorder characterized by the triad of situs inversus, including dextrocardia, bronchiectasis and paranasal sinusitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15025618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Kartagener's syndrome is an inherited disease characterized by a triad of symptoms: bronchiectasis, situs inversus and sinusitis resulting from defective cilial motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17408950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Ear, nose and throat symptoms and signs were studied in 15 patients with Kartagener's syndrome: a triad consisting of chronic rhinosinusitis, chronic bronchitis with bronchiectasis, and situs inversus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6984375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Kartagener syndrome (a clinical variant of primary ciliary dyskinesia) is a recessive autossomical disease characterized by the triad of chronic sinusitis, bronchiectasis and situs inversus with dextrocardia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17725169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Kartagener Syndrome is a rare autosomal recessive disorder consisting of triad of sinusitis, bronchiectasis and situs inversus with dextrocardia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19529061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Kartagener syndrome (KS), an autosomal recessively inherited disease, is characterized by the triad of situs inversus, bronchiectasis and sinusitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Kartagener's syndrome is an inherited disease characterized by a triad of symptoms--bronchiectasis, situs inversus and sinusitis--and is classified as an immotile cilia syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9927835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Kartagener's syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24019633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "A comprehensive clinicomorphological examination of 24 children with Zivert-Kartagener syndrome ascertained the complete triad (bronchiectasis, maldevelopment of the sinuses and transposition of the viscera) in all of them", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8290523", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 458, "text": "The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22966723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "We present a case of a patient with clinically definite ALS, who had earlier suffered from Kartagener syndrome, which is characterized by the triad comprising chronic sinusitis, bronchiectasis, and situs inversus. Recent linkage and mutational analyses identified several genes that are responsible for Kartagener syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20550487", "endSection": "abstract" } ] }, { "body": "Which disease is associated with the ectopic expression of the protein encoded by the gene DUX4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24232919", "http://www.ncbi.nlm.nih.gov/pubmed/21484336", "http://www.ncbi.nlm.nih.gov/pubmed/21951698", "http://www.ncbi.nlm.nih.gov/pubmed/23966205", "http://www.ncbi.nlm.nih.gov/pubmed/22718021", "http://www.ncbi.nlm.nih.gov/pubmed/19829708", "http://www.ncbi.nlm.nih.gov/pubmed/23777630", "http://www.ncbi.nlm.nih.gov/pubmed/24075187", "http://www.ncbi.nlm.nih.gov/pubmed/22536400", "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "http://www.ncbi.nlm.nih.gov/pubmed/22798623", "http://www.ncbi.nlm.nih.gov/pubmed/17984056", "http://www.ncbi.nlm.nih.gov/pubmed/22892954", "http://www.ncbi.nlm.nih.gov/pubmed/24030947", "http://www.ncbi.nlm.nih.gov/pubmed/23108159", "http://www.ncbi.nlm.nih.gov/pubmed/23644600", "http://www.ncbi.nlm.nih.gov/pubmed/21529284", "http://www.ncbi.nlm.nih.gov/pubmed/23143600" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3832170", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1317909", "o": "http://linkedlifedata.com/resource/umls/label/A3832170" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3832170", "o": "DUX4 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1317909", "o": "http://linkedlifedata.com/resource/umls/label/A3840964" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3840964", "o": "double homeobox, 4 protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3840964", "o": "MeSH" } ], "ideal_answer": [ "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat." ], "exact_answer": [ "Facioscapulohumeral dystrophy", "FSHD" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.uniprot.org/uniprot/DUX4_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category" ], "type": "factoid", "id": "550f0e4c6a8cde6b72000003", "snippets": [ { "offsetInBeginSection": 571, "offsetInEndSection": 667, "text": "e expression of DUX4 has been confirmed in both FSHD cells and biopsies by several laboratories.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205", "endSection": "abstract" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1516, "text": "These results indicate that molecular markers of the disease are already expressed during fetal life, thus opening a new field of investigation for mechanisms leading to FSHD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 992, "text": "DUX4, the primary candidate for FSHD pathogenesis, is upregulated over ten-fold in FSHD myoblasts and myotubes with short telomeres, and its expression is inversely proportional to telomere length. FSHD may be the first known human disease in which TPE contributes to age-related phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23644600", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 319, "text": "Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology. However, no one knows what triggers muscle defect and when alteration arises. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777630", "endSection": "abstract" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1161, "text": "Recent studies have provided a plausible disease mechanism for FSHD in which FSHD results from inappropriate expression of the germline transcription factor DUX4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892954", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 485, "text": "Recent studies have proposed that FSHD pathology is caused by the misexpression of the DUX4 (double homeobox 4) gene resulting in production of a pathogenic protein, DUX4-FL, which has been detected in FSHD, but not in unaffected control myogenic cells and muscle tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22798623", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "DUX4, a homeobox-containing gene present in a tandem array, is implicated in facioscapulohumeral muscular dystrophy (FSHD), a dominant autosomal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22718021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Facioscapulohumeral Disease (FSHD) is a dominantly inherited progressive myopathy associated with aberrant production of the transcription factor, Double Homeobox Protein 4 (DUX4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22536400", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 379, "text": " A DUX4 transcript derived from the last repeat unit in a contracted array is associated with pathogenesis but it is unclear how.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21951698", "endSection": "abstract" }, { "offsetInBeginSection": 2021, "offsetInEndSection": 2304, "text": "DUX4's pathogenic effect in FSHD may occur transiently at or before the stage of myoblast formation to establish a cascade of gene dysregulation. This contrasts with the current emphasis on toxic effects of experimentally upregulated DUX4 expression at the myoblast or myotube stages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21951698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Double homeobox 4 (DUX4) is a candidate disease gene for facioscapulohumeral dystrophy (FSHD), one of the most common muscular dystrophies characterized by progressive skeletal muscle degeneration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21529284", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 648, "text": "In FSHD, the combination of inefficient chromatin silencing of the D4Z4 repeat and polymorphisms on the FSHD-permissive alleles that stabilize the DUX4 mRNAs emanating from the repeat result in inappropriate DUX4 protein expression in muscle cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 464, "text": "In facioscapulohumeral muscular dystrophy, recent findings implicate a stabilized DUX4 transcript within the contracted D4Z4 repeats, opening the door for an RNA interference treatment strategy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21484336", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1327, "text": " Aberrant expression of DUX4 from the last unit of the D4Z4 array has been proposed to be the cause of FSHD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24232919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Paired-like homeodomain transcription factor 1 (PITX1) was proposed to be part of the disease mechanisms of facioscapulohumeral muscular dystrophy (FSHD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24232919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array on chromosome 4 to a size of 1-10 units. The residual number of D4Z4 units inversely correlates with clinical severity, but significant clinical variability exists. Each unit contains a copy of the DUX4 retrogene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Facioscapulohumeral muscular dystrophy has been genetically linked to reduced numbers (\u2264 8) of D4Z4 repeats at 4q35 combined with 4A(159/161/168) DUX4 polyadenylation signal haplotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24030947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent adult muscular dystrophies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 667, "text": "We mainly focus on DUX4 isoform expression because the expression of DUX4 has been confirmed in both FSHD cells and biopsies by several laboratories.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23966205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Facio-scapulo-humeral dystrophy (FSHD) results from deletions in the subtelomeric macrosatellite D4Z4 array on the 4q35 region. Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 713, "text": "Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy characterized by an asymmetric progressive weakness and wasting of the facial, shoulder and upper arm muscles, frequently accompanied by hearing loss and retinal vasculopathy. FSHD is an autosomal dominant disease linked to chromosome 4q35, but the causative gene remains controversial. DUX4 is a leading candidate gene as causative of FSHD. However, DUX4 expression is extremely low in FSHD muscle, and there is no DUX4 animal model that mirrors the pathology in human FSHD. Here, we show that the misexpression of very low levels of human DUX4 in zebrafish development recapitulates the phenotypes seen in human FSHD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23108159", "endSection": "abstract" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1595, "text": "Our results suggest that the misexpression of DUX4-fl, even at extremely low level, can recapitulate the phenotype observed in FSHD patients in a vertebrate model. These results strongly support the current hypothesis for a role of DUX4 in FSHD pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23108159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "DUX4, a homeobox-containing gene present in a tandem array, is implicated in facioscapulohumeral muscular dystrophy (FSHD), a dominant autosomal disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22718021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Facioscapulohumeral Disease (FSHD) is a dominantly inherited progressive myopathy associated with aberrant production of the transcription factor, Double Homeobox Protein 4 (DUX4). The expression of DUX4 depends on an open chromatin conformation of the D4Z4 macrosatellite array and a specific haplotype on chromosome 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22536400", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 491, "text": "Even when these requirements are met, DUX4 transcripts and protein are only detectable in a subset of cells indicating that additional constraints govern DUX4 production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22536400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) has an unusual pathogenic mechanism. FSHD is caused by deletion of a subset of D4Z4 macrosatellite repeat units in the subtelomere of chromosome 4q. Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 390, "text": "Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19829708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contractions of the D4Z4 repeat array in the subtelomeric region of chromosome 4q.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17984056", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 591, "text": "In addition, we showed that the double homeobox 4 gene (DUX4) that maps within the D4Z4 repeat unit was up-regulated in patient myoblasts at both mRNA and protein level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17984056", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1156, "text": "Our results suggest that up-regulation of both DUX4 and PITX1 in FSHD muscles may play critical roles in the molecular mechanisms of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17984056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23143600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "endSection": "abstract" } ] }, { "body": "Which G protein is essential in the formation and function of lamellipodia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11709084", "http://www.ncbi.nlm.nih.gov/pubmed/19801976", "http://www.ncbi.nlm.nih.gov/pubmed/24265417", "http://www.ncbi.nlm.nih.gov/pubmed/9301423", "http://www.ncbi.nlm.nih.gov/pubmed/11230698" ], "ideal_answer": [ "Recruitment of the small G-protein Rac1 to the plasma membrane is essential in inducing the local formation of specialized cellular processes termed lamellipodia." ], "exact_answer": [ "Rac1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011554", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019204", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020744" ], "type": "factoid", "id": "5319ac36b166e2b806000031", "snippets": [ { "offsetInBeginSection": 1039, "offsetInEndSection": 1329, "text": "We specifically identified that the Spa homology domain (aa 250-420) of GIT1 is required for GIT1-cortactin complex localization to the leading edge. The mechanisms involved extracellular signal-regulated kinases 1 and 2-mediated Cortactin-S405 phosphorylation and activation of Rac1/Cdc42.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265417", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 586, "text": "We demonstrated the utility of this system with LAD constructs that can recruit the small G-protein Rac1 to the plasma membrane and induce the local formation of lamellipodia in response to focal illumination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19801976", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1122, "text": "We found that fibroblasts from EDG-1 null embryos did not migrate toward PDGF or SPP, and inhibition of motility correlated with defective activation of the small guanosine triphosphatase Rac, which is required for lamellipodia formation and directional locomotion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11709084", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 510, "text": "Deletion of edg-1 or inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also activation of the small guanosine triphosphatase Rac, which is essential for protrusion of lamellipodia and forward movement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11230698", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 714, "text": "Evidence from these models indicates that migration is a highly complex process, which is likely to involve the tightly controlled spatial and temporal interaction of multiple factors:", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9301423", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1479, "text": "(v) molecules which regulate cytoskeletal function (e.g. Rac), which allows the formation of specialized cellular processes termed lamellipodia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9301423", "endSection": "abstract" } ] }, { "body": "Which are the main functions of the APOBEC3 family of proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22915799", "http://www.ncbi.nlm.nih.gov/pubmed/15466872", "http://www.ncbi.nlm.nih.gov/pubmed/17439959", "http://www.ncbi.nlm.nih.gov/pubmed/21966267", "http://www.ncbi.nlm.nih.gov/pubmed/22720156", "http://www.ncbi.nlm.nih.gov/pubmed/22203821", "http://www.ncbi.nlm.nih.gov/pubmed/15994766", "http://www.ncbi.nlm.nih.gov/pubmed/16557012" ], "ideal_answer": [ "The APOBEC3 family of cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1), and endogenous transposable elements, such as LINE-1 and Alu retrotransposons." ], "exact_answer": [ [ "host-mediated defense against exogenous viruses" ], [ "defense against endogenous transposable elements" ] ], "concepts": [ "http://www.uniprot.org/uniprot/ABEC3_MOUSE", "http://www.uniprot.org/uniprot/ABEC3_CRILO", "http://www.uniprot.org/uniprot/ABEC3_RAT" ], "type": "list", "id": "54dfc6501388e8454a000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The APOBEC3 cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1) and endogenous transposable elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22915799", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 82, "text": "the identification of APOBEC3G (A3G) as a potent restriction factor of HIV-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22720156", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 631, "text": "additional A3 family members have been identified as antiviral proteins, mechanistic details of the restrictive capacity of these proteins have been elucidated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22720156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Human APOBEC3 (A3) proteins are cellular cytidine deaminases that potently restrict the replication of retroviruses by hypermutating viral cDNA and/or inhibiting reverse transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22203821", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 367, "text": "A3F and A3G are the most potent inhibitors of HIV-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22203821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21966267", "endSection": "title" }, { "offsetInBeginSection": 626, "offsetInEndSection": 727, "text": "we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21966267", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1374, "text": "Our results indicate that APOBEC3A is a previously unrecognized antiviral factor that targets primate lentiviruses specifically in myeloid cells and that acts during the early phases of infection directly in target cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21966267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Foamy virus Bet proteins function as novel inhibitors of the APOBEC3 family of innate antiretroviral defense factors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15994766", "endSection": "title" }, { "offsetInBeginSection": 518, "offsetInEndSection": 727, "text": "This inhibition correlated with the packaging of inhibitory APOBEC3 proteins into PFV virions, due to a specific PFV Gag/APOBEC3 interaction, and resulted in the G to A hypermutation of PFV reverse transcripts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15994766", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "[Antiviral defense by APOBEC3 family proteins].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16557012", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17439959", "endSection": "title" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1314, "text": "These findings raise the possibility that the different APOBEC3 family members function to neutralize specific lentiviruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15466872", "endSection": "abstract" } ] }, { "body": "Which histone modifications are associated with constitutive heterochromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17710556", "http://www.ncbi.nlm.nih.gov/pubmed/11850619", "http://www.ncbi.nlm.nih.gov/pubmed/11356363", "http://www.ncbi.nlm.nih.gov/pubmed/16705169", "http://www.ncbi.nlm.nih.gov/pubmed/18004385", "http://www.ncbi.nlm.nih.gov/pubmed/20599948", "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "http://www.ncbi.nlm.nih.gov/pubmed/14506132", "http://www.ncbi.nlm.nih.gov/pubmed/18987983", "http://www.ncbi.nlm.nih.gov/pubmed/19786836", "http://www.ncbi.nlm.nih.gov/pubmed/15368356", "http://www.ncbi.nlm.nih.gov/pubmed/20562223", "http://www.ncbi.nlm.nih.gov/pubmed/21267468", "http://www.ncbi.nlm.nih.gov/pubmed/12581305", "http://www.ncbi.nlm.nih.gov/pubmed/21803857" ], "triples": [ { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q58E49", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0000792" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5135384534390011", "o": "Histone deacetylase" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0000792", "o": "heterochromatin" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q58E49", "o": "http://purl.uniprot.org/go/0000792" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0000792", "o": "heterochromatin" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0000792", "o": "http://www.geneontology.org/go#GO:0000792" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/O09106", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0000792" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_4F30393130360026", "o": "HD1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F30393130360026", "o": "Histone deacetylase 1" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/O09106", "o": "http://purl.uniprot.org/go/0000792" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/P29227", "o": "http://purl.uniprot.org/go/0016568" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_50323932323700B", "o": "HP1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P29227", "o": "http://linkedlifedata.com/resource/#_50323932323700B" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0016568", "o": "chromatin modification" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_50323932323700B", "o": "Heterochromatin protein 1" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0016568", "o": "http://www.geneontology.org/go#GO:0016568" } ], "ideal_answer": [ "Strong methylation at H3 lysine 9 occurred preferentially in heterochromatic chromocenters of Arabidopsis nuclei. In general, heterochromatin has been linked to trimethylation of H3 at lysine 9 and parsimony analysis reveal that histone H3K9 methylation is, next to histone deacetylation, the evolutionary most stable heterochromatic mark. Classical histone modifications associated with heterochromatin also include H3K27me1 and H3K27me2. H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin. Other histone methylation marks usually found in constitutive heterochromatin are H4K20me3, H3K9me3, and H3K79me3. H3S10P is a good marker of pericentromeric heterochromatin.", "H3K9 methylation\nH3S10 phosphorylation\nH3K79 and H4K20 methylation" ], "exact_answer": [ [ "H3K9Me1", "H3K9Me2", "H3K9me3", "H3K9 trimethylation" ], [ "H3K27me1" ], [ "H3K27me2" ], [ "H4K20me3", "H4K20 trimethylation" ], [ "H3K79me3", "H3K79 methylation" ], [ "H3S10", "H3S10 phosphorylation" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056284", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001207", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034729", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032452", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031445", "http://www.uniprot.org/uniprot/CBX5_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033182", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900049", 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"http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016578" ], "type": "list", "id": "52e0c9a298d0239505000010", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 432, "text": "Remarkably, in mammalian somatic cells, H3S10P initiates in the pericentromeric heterochromatin during the late G2 phase, and phosphorylation spreads throughout the chromosomes arms in prophase, being maintained until the onset of anaphase when it gets dephosphorylated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "endSection": "abstract" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1744, "text": "Based on these findings, we believe that H3S10P is a good marker of pericentromeric heterochromatin, especially in the late 1- and 2-cell stages as it labels both parental genomes and that it can be used to further investigate epigenetic regulation and heterochromatin mechanisms in early preimplantation embryos", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 120, "text": "3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "endSection": "title" }, { "offsetInBeginSection": 8, "offsetInEndSection": 102, "text": "H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "title" }, { "offsetInBeginSection": 393, "offsetInEndSection": 664, "text": "We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1117, "text": "We show that H3K36me3 deposition within this large heterochromatin domain does not correlate with transcription events, suggesting the existence of an alternative pathway for the deposition of this histone modification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1275, "text": "In addition, we demonstrate that H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in mouse embryonic stem cells and fibroblasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1381, "text": "This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1584, "text": "Our data suggest that H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin, in combination with other histone modifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 174, "text": "accumulation of histone H3.3 and euchromatic histone modifications in pericentromeric heterochromatin in response to a decrease in DNA methylation levels", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599948", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 440, "text": "In this study, we show that inhibition of DNA methylation in mouse fibroblast cells affects histone modification and the subnuclear localization of histone H3.3 in a cell cycle-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599948", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1325, "text": "Moreover, we found that histone H3.3 was deposited on the pericentromeric heterochromatin prior to the accumulation of the euchromatic histone modifications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599948", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 623, "text": "Classical histone modifications associated with heterochromatin, including H3K9me2, H3K27me1 and H3K27me2, were distributed throughout both A and B chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18987983", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 790, "text": "However, H3K27me2 showed a reduced level on the B chromosome compared with the A chromosomes and was not associated with some classes of constitutive heterochromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18987983", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 388, "text": "Recently analyzed H3K9 methyltransferases (HMTases) as SUV39H1, Clr4p, DIM-5, Su(var)3-9 or SUVH2 are responsible for the establishment of histone H3 lysine 9 methylation (H3K9me), which is intimately connected with heterochromatinization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17710556", "endSection": "abstract" }, { "offsetInBeginSection": 23, "offsetInEndSection": 92, "text": "heterochromatic histone H3K9 methyltransferases left its marks behind", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17710556", "endSection": "title" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1092, "text": "Compilation and parsimony analysis reveal that histone H3K9 methylation is, next to histone deacetylation, the evolutionary most stable heterochromatic mark, which is established by at least two subfamilies of specialized heterochromatic HMTases in almost all studied eukaryote", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17710556", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 445, "text": "Trimethylated H3(K9) marks pericentromeric constitutive heterochromatin and the male Y chromosome, while H2A.Z is dramatically reduced at these chromosomal locations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16705169", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 754, "text": "Of eight tested antibodies, the one for histone H4 acetylated at lysine 4, 8, 12, or 16 was best for distinguishing constitutive heterochromatin from unexpressed euchromatin, but differences in the extent of immunoprecipitation of these two types of chromatin were only modest, although highly reproducible", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15368356", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1465, "text": "In addition, immunocytochemical analysis was done with an antibody to heterochromatin protein 1alpha (HP1alpha), whose preferential binding to heterochromatin has been linked to trimethylation of H3 at lysine 9", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15368356", "endSection": "abstract" }, { "offsetInBeginSection": 1467, "offsetInEndSection": 1756, "text": "Our combined ChIP and immunocytochemical results suggest that factors other than hypoacetylation of the N-terminal tails of H4 and hypermethylation of H3 at lysine 9 can play an important role in determining whether a chromatin sequence in mammalian cells is constitutively heterochromatic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15368356", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 819, "text": "To test for the putative heterochromatinization, we quantitated chromatin immunoprecipitation with an antibody for acetylated histone H4 that discriminates between constitutive heterochromatin and unexpressed euchromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14506132", "endSection": "abstract" }, { "offsetInBeginSection": 38, "offsetInEndSection": 117, "text": "high methylation of H3 lysine 9 is dispensable for constitutive heterochromatin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581305", "endSection": "title" }, { "offsetInBeginSection": 546, "offsetInEndSection": 729, "text": "Strong methylation at H3 lysine 4 was restricted to euchromatin, while strong methylation at H3 lysine 9 occurred preferentially in heterochromatic chromocenters of Arabidopsis nuclei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12581305", "endSection": "abstract" } ] }, { "body": "What is the main application of SWATH-MS in proteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23227840", "http://www.ncbi.nlm.nih.gov/pubmed/23322582", "http://www.ncbi.nlm.nih.gov/pubmed/22261725", "http://www.ncbi.nlm.nih.gov/pubmed/23811049" ], "ideal_answer": [ "Using the method called SWATH-MS one might ask sample sets for the presence and quantity of essentially any protein of interest." ], "exact_answer": [ "The identification and quantification of any protein." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "factoid", "id": "530cf54dab4de4de0c00000c", "snippets": [ { "offsetInBeginSection": 829, "offsetInEndSection": 992, "text": "it is a valuable resource for the selection of candidate proteotypic peptides for targeted proteomic experiments via Selected Reaction Monitoring (SRM) or SWATH-MS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23811049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "SWATH-MS is a data-independent acquisition method that generates, in a single measurement, a complete recording of the fragment ion spectra of all the analytes in a biological sample for which the precursor ions are within a predetermined m/z versus retention time window.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322582", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 1007, "text": "ew strategies, such as SWATH\u2122 MS, which allows us to systematically characterize and quantify query sample sets of 'any protein of interest' in complex biological samples,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227840", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 516, "text": "Here we present a new strategy that systematically queries sample sets for the presence and quantity of essentially any protein of interest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261725", "endSection": "abstract" } ] }, { "body": "Do selenoproteins and selenium play a role in prostate cancer prevention?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19074884", "http://www.ncbi.nlm.nih.gov/pubmed/15875088", "http://www.ncbi.nlm.nih.gov/pubmed/19690186", "http://www.ncbi.nlm.nih.gov/pubmed/20852007", "http://www.ncbi.nlm.nih.gov/pubmed/20424130", "http://www.ncbi.nlm.nih.gov/pubmed/22072582", "http://www.ncbi.nlm.nih.gov/pubmed/19299660", "http://www.ncbi.nlm.nih.gov/pubmed/23133653", "http://www.ncbi.nlm.nih.gov/pubmed/16690748", "http://www.ncbi.nlm.nih.gov/pubmed/17160069" ], "ideal_answer": [ "No, although initial epidemiological studies on humans and on animal and cell- based models indicated that selenoproteins may be protecting against prostate cancer, more research is needed to improve the understanding of selenium metabolism and requirements for optimal health." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051140", "http://www.disease-ontology.org/api/metadata/DOID:10283" ], "type": "yesno", "id": "515ed87c298dcd4e51000032", "snippets": [ { "offsetInBeginSection": 1115, "offsetInEndSection": 1402, "text": "The selenoprotein-deficient mice exhibited accelerated development of lesions associated with prostate cancer progression, implicating selenoproteins in cancer risk and development and raising the possibility that selenium prevents cancer by modulating the levels of these selenoproteins", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690748", "endSection": "sections.0" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1564, "text": "Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17160069", "endSection": "sections.0" }, { "offsetInBeginSection": 1783, "offsetInEndSection": 2110, "text": "In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074884", "endSection": "sections.0" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1566, "text": "Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20852007", "endSection": "sections.0" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1767, "text": "This study provides evidence that SEP15 genetic variation may influence PCa mortality. Additionally, the association of selenium with PCa mortality was modified by a variant, suggesting the possibility that some men with PCa may benefit more from selenium than others, depending on their genotype.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20424130", "endSection": "sections.0" }, { "offsetInBeginSection": 1619, "offsetInEndSection": 1752, "text": "We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19690186", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "The recently completed Selenium and Vitamin E Cancer Prevention Trial (SELECT) was one of the largest human cancer prevention trials ever undertaken. Its purpose was to assess the role of selenium and vitamin E in prostate cancer prevention, but SELECT found no decline in prostate cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19299660", "endSection": "sections.0" }, { "offsetInBeginSection": 325, "offsetInEndSection": 928, "text": "We studied Se levels in whole blood, plasma and prostate of 32 PC and 40 benign prostate hyperplasia (BPH) patients and in the control group composed of 39 healthy subjects. The selenoenzyme glutathione peroxidase (GSH-Px) was also measured in the patients' red cells, plasma and prostate tissue. Se concentration in whole blood and plasma in both groups of patients was lower as compared with controls, while in prostate gland it was significantly higher in PC than in BPH patients and controls. Red cell GSH-Px activity was the same in PC patients and controls but significantly lower in BPH patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15875088", "endSection": "sections.0" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1553, "text": "Of particular interest was the positive correlation between tissue GPx activity and Gleason score, with this relationship achieving statistical significance among African-Americans (r\u2009=\u20090.67, P\u2009=\u20090.02)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22072582", "endSection": "sections.0" } ] }, { "body": "What can Nothobranchius furzeri be used as a model system for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19302373", "http://www.ncbi.nlm.nih.gov/pubmed/19052641", "http://www.ncbi.nlm.nih.gov/pubmed/17049789", "http://www.ncbi.nlm.nih.gov/pubmed/16687936", "http://www.ncbi.nlm.nih.gov/pubmed/16164422" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2174134", "o": "105023" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1048677", "o": "http://linkedlifedata.com/resource/umls/label/A2174134" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1048677", "o": "http://linkedlifedata.com/resource/umls/label/A2174134" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2174134", "o": "Nothobranchius furzeri" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A2174134", "o": "NCBI Taxonomy" } ], "ideal_answer": [ "N. furzeri an interesting model system to investigate the effects of experimental manipulations on longevity and age-related pathologies.\nN. furzeri could represent a model system for studying the genetic control of life-history traits in natural populations.\nN. furzeri could be a very useful model for comparative genomics of aging.\nIt can be employed to test the effects of experimental manipulation on aging and apharmacological research." ], "exact_answer": [ "aging research" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023421" ], "type": "factoid", "id": "52bf217003868f1b0600001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "The short-lived annual fish Nothobranchius furzeri shows extremely short captive life span and accelerated expression of age markers, making it an interesting model system to investigate the effects of experimental manipulations on longevity and age-related pathologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19302373", "endSection": "abstract" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1527, "text": "Owing to large differences in aging phenotypes in different lines, N. furzeri could represent a model system for studying the genetic control of life-history traits in natural populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19052641", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1362, "text": "It is very close to the Japanese Medaka, and close to the pufferfishes and stickleback and might represent a very useful model for comparative genomics of aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17049789", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1111, "text": "In the last three years, N. furzeri has moved from biological curiosity to a promising model system for drug validation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17049789", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 1244, "text": " This result identifies resveratrol as the first molecule which consistently retards aging in organisms as diverse as yeast, worm, fly and fish, but it also reveals the potential of this short-lived fish as an animal model for pharmacological research. Moreover, being related to stickleback (Gasterosteus aculeatus) the \"pufferfishes\" Takifugu and Tetraodon, and even more closely related to medaka (Oryzias latipes), it can greatly beneficiate from the recent development of genomic resources for these fish models and in the future become a complete model system for the aging research community.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16687936", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1610, "text": "These fishes can become excellent models for aging studies. They can be employed to test the effects of experimental manipulation on aging at a pace comparable with that of Drosophila and to probe the effects of natural selection on the evolution of aging-related genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16164422", "endSection": "abstract" } ] }, { "body": "What is the function of TALENs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22624882", "http://www.ncbi.nlm.nih.gov/pubmed/23027955", "http://www.ncbi.nlm.nih.gov/pubmed/23000899", "http://www.ncbi.nlm.nih.gov/pubmed/23555929" ], "ideal_answer": [ " These chimeric enzymes can be used to introduce a double strand break at a specific genomic site which then can become the substrate for error-prone non-homologous end joining (NHEJ), generating mutations at the site of cleavage. Artificial transcription activator-like effector nucleases (TALENs) provide a powerful new approach for targeted zebrafish genome editing and functional genomic applications. Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease domain fused to a DNA binding domain which is engineered to bind to any genomic sequence. Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs.", "Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease domain fused to a DNA binding domain which is engineered to bind to any genomic sequence. These chimeric enzymes can be used to introduce a double strand break at a specific genomic site which then can become the substrate for error-prone non-homologous end joining (NHEJ), generating mutations at the site of cleavage. TALENs provide a powerful new approach for targeted genome editing and functional genomic applications." ], "type": "summary", "id": "515dc691298dcd4e5100001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23027955", "endSection": "sections.0" } ] }, { "body": "Has protein citrullination been implicated in rheumatoid arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24498912", "http://www.ncbi.nlm.nih.gov/pubmed/25182207", "http://www.ncbi.nlm.nih.gov/pubmed/25475141", "http://www.ncbi.nlm.nih.gov/pubmed/24763532", "http://www.ncbi.nlm.nih.gov/pubmed/24724574", "http://www.ncbi.nlm.nih.gov/pubmed/25116951", "http://www.ncbi.nlm.nih.gov/pubmed/24823363", "http://www.ncbi.nlm.nih.gov/pubmed/25520183", "http://www.ncbi.nlm.nih.gov/pubmed/25515746", "http://www.ncbi.nlm.nih.gov/pubmed/24782594", "http://www.ncbi.nlm.nih.gov/pubmed/25355199", "http://www.ncbi.nlm.nih.gov/pubmed/24497204" ], "ideal_answer": [ "Yes, protein citrullination been implicated in rheumatoid arthritis." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:848", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001168", "http://www.biosemantics.org/jochem#4275495", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001171", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://www.biosemantics.org/jochem#4249918", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002956", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0019240" ], "type": "yesno", "id": "54d796f93706e8952800001e", "snippets": [ { "offsetInBeginSection": 30, "offsetInEndSection": 193, "text": ": Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25520183", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 933, "text": "Current literature suggests that increased levels of citrullinated proteins are found in several if not all inflammatory diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25520183", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 377, "text": "Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing RA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25515746", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 306, "text": "Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation in general. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25475141", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1180, "text": "Some ACPA are remarkably effective as diagnostics in autoimmune disorders, most notably rheumatoid arthritis (RA). Several ACPA can be observed before other clinical RA manifestations are apparent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25355199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein/peptide autoantibodies (ACPAs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182207", "endSection": "title" }, { "offsetInBeginSection": 1248, "offsetInEndSection": 1467, "text": "The implications of citrullination affecting integrin binding in disease open up a new area of study and might have implications for the pathogenesis of inflammatory diseases like rheumatoid arthritis and periodontitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116951", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 777, "text": "In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24782594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Citrullinated collagen II (CII) is a well-known autoantigen in rheumatoid arthritis (RA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24823363", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 501, "text": "Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Protein citrullination is a posttranslational modification that has attracted increased attention, especially for its involvement in rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24724574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Identification of citrullinated cellular fibronectin in synovial fluid from patients with rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24498912", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 206, "text": "Cellular fibronectin (cFn) has been implicated in the pathogenesis of rheumatoid arthritis (RA), and we previously demonstrated the presence of citrullinated cFn in rheumatoid synovial tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24498912", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 313, "text": ". In rheumatoid arthritis, PAD4 and protein citrullination are increased in inflamed joints, and anti-citrullinated protein antibodies (ACPAs) form against citrullinated antigens are formed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24497204", "endSection": "abstract" } ] }, { "body": "Show results of randomised controlled trials for certolizumab pegol.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24092417", "http://www.ncbi.nlm.nih.gov/pubmed/21328299", "http://www.ncbi.nlm.nih.gov/pubmed/22165979", "http://www.ncbi.nlm.nih.gov/pubmed/21047485" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00672828", "o": "http://data.linkedct.org/resource/intervention/25702" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00672828", "o": "Trial NCT00672828" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/25702", "o": "Intervention #25702 (Drug:Liquid Certolizumab pegol)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/25702", "o": "Liquid Certolizumab pegol" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00566852", "o": "http://data.linkedct.org/resource/intervention/25703" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/25703", "o": "Intervention #25703 (Drug:Liquid Certolizumab pegol)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00566852", "o": "Trial NCT00566852" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/25703", "o": "Liquid Certolizumab pegol" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00106327", "o": "http://data.linkedct.org/resource/intervention/2481" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/2481", "o": "Intervention #2481 (Drug:CDP870 (Certolizumab pegol))" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/2481", "o": "CDP870 (Certolizumab pegol)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00106327", "o": "Trial NCT00106327" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00626067", "o": "http://data.linkedct.org/resource/intervention/27818" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/27818", "o": "Certolizumab pegol (CDP870)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/27818", "o": "Intervention #27818 (Biological:Certolizumab pegol (CDP870))" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00626067", "o": "Trial NCT00626067" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00149071", "o": "http://data.linkedct.org/resource/intervention/2952" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/2952", "o": "Intervention #2952 (Drug:Certolizumab Pegol (CDP870))" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/2952", "o": "Certolizumab Pegol (CDP870)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00149071", "o": "Trial NCT00149071" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00717782", "o": "http://data.linkedct.org/resource/intervention/25601" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/25601", "o": "Intervention #25601 (Biological:certolizumab pegol (CDP870))" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/25601", "o": "certolizumab pegol (CDP870)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00717782", "o": "Trial NCT00717782" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00564967", "o": "http://data.linkedct.org/resource/intervention/2954" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/2954", "o": "Intervention #2954 (Drug:Certolizumab pegol (CDP870))" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00564967", "o": "Trial NCT00564967" }, { "p": "http://data.linkedct.org/resource/linkedct/acronym", "s": "http://data.linkedct.org/resource/trials/NCT00564967", "o": "IS1" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/2954", "o": "Certolizumab pegol (CDP870)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00564967", "o": "http://data.linkedct.org/resource/intervention/2955" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/2955", "o": "Certolizumab pegol (cimzia\u00ae)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/2955", "o": "Intervention #2955 (Drug:Certolizumab pegol (cimzia\u00ae))" } ], "ideal_answer": [ "Improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.\nRandomised controlled trials (RCTs) of CZP have demonstrated rapid improvements in workplace and home productivity." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016449" ], "type": "summary", "id": "535d613f7d100faa09000002", "snippets": [ { "offsetInBeginSection": 654, "offsetInEndSection": 1387, "text": "RESULTS: 4049 RA patients who received CZP were included in the safety pooling; total exposure 9277 PY, mean exposure 2.1 years (range 0.04-7.6). SIE, most frequently pneumonia (IR 0.73/100 PY), were the most common serious AE, occurring more frequently in CZP compared to placebo-treated patients in RCT (IR 5.61/100 PY vs 1.35/100 PY, odds ratio (OR) 4.35, 95% CI 0.65 to 29.30). SIE rates were lower in the CZP-treated population including OLE (ER 4.33/100 PY). 44 patients developed tuberculosis (IR 0.47/100 PY), 39 from high endemic regions. 58 deaths occurred in CZP-exposed patients (IR 0.63/100 PY) and 70 developed malignancies excluding non-melanoma skin cancer (IR 0.76/100 PY), including five lymphomas (IR 0.05/100 PY).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24092417", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1277, "text": "As well as displaying clinical efficacy, there is evidence to suggest that CZP has unique characteristics, including reduced transfer across the placenta and reduced frequency of injection site reactions. Furthermore, randomised controlled trials (RCTs) of CZP have demonstrated rapid improvements in workplace and home productivity in patients contributing to reducing the significant socioeconomic burden of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22165979", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 452, "text": "To assess the effectiveness and safety of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease modifying anti-rheumatic drugs (DMARDs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21328299", "endSection": "abstract" }, { "offsetInBeginSection": 2633, "offsetInEndSection": 2998, "text": " With an overall high grade of evidence this review revealed an improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol.\u00a0Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21328299", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 2772, "text": "The clinical evidence was derived from two multicentre blinded randomised controlled trials (RCTs) comparing CZP + MTX to placebo + MTX (the RAPID 1 and RAPID 2 trials). RAPID 1 lasted 52 weeks with 982 patients and RAPID 2 24 weeks with 619 patients. Evidence for clinical effectiveness of CZP in mono-therapy came from the 24-week FAST4WARD trial with 220 patients that compared CZP (400 mg every 4 weeks) versus placebo. The three key RCTs demonstrated statistically significant superiority of CZP + MTX versus placebo + MTX and of CZP versus placebo with respect to a variety of outcomes including ACR 20, ACR 50 and ACR 70 measures and quality of life measures at 3 and 6 months. On the basis of results from the indirect comparison meta-analyses, the manufacturer suggested that CZP may be at least as effective as other 'biological' DMARD (bDMARD) comparators and, in a few ACR measures at 3 and 6 months, more effective. CZP is an effective therapy for adult RA patients whose disease has failed to respond adequately to cDMARDs including MTX or who are intolerant of MTX. The cost-effectiveness of CZP relative to other bDMARDs is unclear because the economic modelling undertaken may have ignored relevant effectiveness data and potential differences between trial populations, and so may have included effectiveness results that were biased in favour of CZP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047485", "endSection": "abstract" } ] }, { "body": "Which is the mass-tag that reveal the ubiquitination of a lysine residue?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24196352", "http://www.ncbi.nlm.nih.gov/pubmed/24051958", "http://www.ncbi.nlm.nih.gov/pubmed/24142993", "http://www.ncbi.nlm.nih.gov/pubmed/24167568", "http://www.ncbi.nlm.nih.gov/pubmed/24251111", "http://www.ncbi.nlm.nih.gov/pubmed/23682733", "http://www.ncbi.nlm.nih.gov/pubmed/23707720" ], "ideal_answer": [ "Lys-\u025b-Gly-Gly (K-\u025b-GG) is the remnant produced by trypsin digestion of proteins having ubiquitinated lysine side chains." ], "exact_answer": [ "Lys-\u025b-Gly-Gly (K-\u025b-GG) is the remnant produced by trypsin digestion of proteins having ubiquitinated lysine side chains." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025801", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008239", "http://www.uniprot.org/uniprot/ALYS_BPDP1", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031386", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014452", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004842", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016567", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057149", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054875" ], "type": "factoid", "id": "54f2228e64850a5854000002", "snippets": [ { "offsetInBeginSection": 191, "offsetInEndSection": 449, "text": "antibodies that recognize the Lys-\u025b-Gly-Gly (K-\u025b-GG) remnant produced by trypsin digestion of proteins having ubiquitinated lysine side chains have markedly improved the ability to enrich and detect endogenous ubiquitination sites by mass spectrometry (MS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24051958", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 798, "text": "Recent publications have also highlighted the use of peptide-level immunoaffinity enrichment of K-GG modified peptides from whole cell lysates for global characterization of ubiquitination sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24142993", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 726, "text": "In this work, levels of lysine ubiquitination were quantitated using a structurally homologous label that is chemically similar to the diglycine (GlyGly) tag, which is left at the ubiquitination site upon trypsinolysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23682733", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 687, "text": "Tandem mass spectrometry (LC-MS/MS) analysis of immunoprecipitated proteins resulted in the identification of five peptides containing ubiquitin (diglycine) modifications on eIF2B\u03b5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707720", "endSection": "abstract" } ] }, { "body": "Which gene is involved in CADASIL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19788051", "http://www.ncbi.nlm.nih.gov/pubmed/22664156", "http://www.ncbi.nlm.nih.gov/pubmed/17854869", "http://www.ncbi.nlm.nih.gov/pubmed/21038489", "http://www.ncbi.nlm.nih.gov/pubmed/19539236", "http://www.ncbi.nlm.nih.gov/pubmed/19018300", "http://www.ncbi.nlm.nih.gov/pubmed/20224942", "http://www.ncbi.nlm.nih.gov/pubmed/17726918", "http://www.ncbi.nlm.nih.gov/pubmed/18313300", "http://www.ncbi.nlm.nih.gov/pubmed/17622327", "http://www.ncbi.nlm.nih.gov/pubmed/21702048", "http://www.ncbi.nlm.nih.gov/pubmed/17996090", "http://www.ncbi.nlm.nih.gov/pubmed/19255248", "http://www.ncbi.nlm.nih.gov/pubmed/22878905", "http://www.ncbi.nlm.nih.gov/pubmed/23308019" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "UMLS_CUI:C0751587" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "cadasil" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "MSH2010_2010_02_22:D046589" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "C499374" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "Notch homolog 3 (Drosophila) protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "NOTCH3 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400718" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400738" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "CADASIL protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "MeSH" } ], "ideal_answer": [ "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene." ], "exact_answer": [ "Notch3 gene" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.disease-ontology.org/api/metadata/DOID:13945", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046589", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "factoid", "id": "5323640b9b2d7acc7e000014", "snippets": [ { "offsetInBeginSection": 71, "offsetInEndSection": 195, "text": "leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664156", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 594, "text": "Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating Fas-Ligand (Fas-L)- induced apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22878905", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 189, "text": ": Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small vessel disease of the brain caused by mutations in the NOTCH3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23308019", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 467, "text": "Mutations in Notch3 gene are linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a disorder characterized by stroke and dementia in young adults", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21702048", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 252, "text": "(CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21038489", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 298, "text": "To evaluate the role of apoptosis in the pathogenesis of brain lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary microangiopathy leading to cognitive decline and dementia, caused by mutations in the NOTCH3 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19788051", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 616, "text": "NOTCH3 (Notch homolog 3), the gene involved in CADASIL, encodes a transmembrane receptor primarily expressed in systemic arterial smooth-muscle cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19539236", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 352, "text": "(CADASIL) is a vascular dementing disease caused by mutations in the NOTCH3 gene, most which are missense mutations leading to an uneven number of cysteine residues in epidermal growth factor-like repeats in the extracellular domain of Notch3 receptor (N3ECD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17622327", "endSection": "abstract" } ] }, { "body": "What is the role of thyroid hormone receptor alpha1 in insulin secretion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22147010", "http://www.ncbi.nlm.nih.gov/pubmed/12869545", "http://www.ncbi.nlm.nih.gov/pubmed/20529852" ], "ideal_answer": [ "Liganded TR(alpha) plays a critical role in beta-cell replication and in expansion of the beta-cell mass. the TRalpha P398H mutation which cannot bind T3, is associated with insulin resistance. Loss of Thra protects mice from high-fat diet-induced hepatic and peripheral insulin resistance." ], "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0050796", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0030073", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/INS_APLCA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011972", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://www.uniprot.org/uniprot/INSR_HUMAN", "http://www.uniprot.org/uniprot/INSR_XENLA", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.uniprot.org/uniprot/INSR_MACMU", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/INSR_RAT", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.uniprot.org/uniprot/INSR_MOUSE", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THA_SALSA" ], "type": "summary", "id": "516beae9298dcd4e5100006b", "snippets": [ { "offsetInBeginSection": 1290, "offsetInEndSection": 1408, "text": "loss of Thra protects mice from high-fat diet-induced hepatic steatosis and hepatic and peripheral insulin resistance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147010", "endSection": "sections.0" }, { "offsetInBeginSection": 1481, "offsetInEndSection": 1745, "text": "liganded TR(alpha) plays a critical role in beta-cell replication and in expansion of the beta-cell mass during postnatal development. Thus, liganded TR(alpha) may be a target for therapeutic strategies that can induce the expansion and regeneration of beta-cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20529852", "endSection": "sections.0" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1327, "text": "the TRalpha P398H mutation is associated with visceral adiposity and insulin resistance", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12869545", "endSection": "sections.0" } ] }, { "body": "Do R-loops tend to form at sites of DNA replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15569610", "http://www.ncbi.nlm.nih.gov/pubmed/7774596", "http://www.ncbi.nlm.nih.gov/pubmed/10082645", "http://www.ncbi.nlm.nih.gov/pubmed/21191184", "http://www.ncbi.nlm.nih.gov/pubmed/25569209", "http://www.ncbi.nlm.nih.gov/pubmed/9119223", "http://www.ncbi.nlm.nih.gov/pubmed/21979917", "http://www.ncbi.nlm.nih.gov/pubmed/9009281", "http://www.ncbi.nlm.nih.gov/pubmed/22195969", "http://www.ncbi.nlm.nih.gov/pubmed/20495385", "http://www.ncbi.nlm.nih.gov/pubmed/21129203", "http://www.ncbi.nlm.nih.gov/pubmed/9150892", "http://www.ncbi.nlm.nih.gov/pubmed/22965135", "http://www.ncbi.nlm.nih.gov/pubmed/25487262", "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "http://www.ncbi.nlm.nih.gov/pubmed/19841062", "http://www.ncbi.nlm.nih.gov/pubmed/22464441", "http://www.ncbi.nlm.nih.gov/pubmed/8798672" ], "ideal_answer": [ "R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins. Physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. One mechanism may be that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed. Thus, the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery.", "We found that overproduction of RecG protein drastically decreased copy numbers of ColE1-type plasmids, which require R-loop formation between the template DNA and a primer RNA transcript (RNA II) for the initiation of replication. ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop. We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. We review evidence suggesting that R-loops are frequent during normal cell growth and that R-loops are critical for the maintenance of genome integrity." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261" ], "type": "yesno", "id": "56e2985951531f7e33000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7774596", "endSection": "abstract" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1340, "text": "We propose that the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8798672", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 344, "text": "The precursor primer RNA exists as a persistent RNA-DNA hybrid, known as an R-loop, formed during transcription through the replication origin (Xu, B., and Clayton, D. A. (1996) EMBO J. 15, 3135-3143).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8798672", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 344, "text": "We found that overproduction of RecG protein drastically decreased copy numbers of ColE1-type plasmids, which require R-loop formation between the template DNA and a primer RNA transcript (RNA II) for the initiation of replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9009281", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 986, "text": "These results suggest that overproduced RecG inhibits the initiation of replication by prematurely resolving the R-loops formed at the replication origin region of these plasmids with its unique helicase activity. The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9009281", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 864, "text": "We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1263, "text": "Furthermore, increased RNaseH expression significantly alleviated genomic instability in deficient fibroblasts suggesting that cotranscriptional R-loops formation contributes to the genesis of replication-dependent DSBs in these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21191184", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 442, "text": "Transcription is an important source of replicative stress and consequently, maintenance of genome integrity requires the protection of chromosomes from the deleterious effects arising from the interaction between nascent RNAs and template DNA, leading to stable DNA-RNA hybrids (R-loop) formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21191184", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 760, "text": "Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 618, "text": "More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stabilit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "R-loop-mediated genomic instability is caused by impairment of replication fork progression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917", "endSection": "title" }, { "offsetInBeginSection": 724, "offsetInEndSection": 922, "text": "When any of these processes are not properly coordinated, aberrant outcomes such as fork reversal and R-loop formation arise and trigger unscheduled recombinogenic events and genome rearrangements. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22464441", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1208, "text": "Many studies show that cells can manage R loop formation with efficiency, and can also process the R-loops already formed in the cell, and by which, the bad effects of R-loops on DNA replication, gene mutation and homologous recombination can be regulated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25487262", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 462, "text": "Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 904, "text": "In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1187, "text": "connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 769, "text": "We show that RNA:DNA hybrids (R-loops) form at sites of transcription/replication collisions and that RNase H1 functions to suppress CFS instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22195969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "R-loops and initiation of DNA replication in human cells: a missing link?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Stable RNA-DNA hybrids (R-loops) prime the initiation of replication in Escherichia coli cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10082645", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 943, "text": "We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 473, "text": "Immediately after infection, RNA-DNA hybrids (R-loops) occur on (at least some) replication origins, with the annealed RNA serving as a primer for leading-strand synthesis in one direction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21129203", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 676, "text": "Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 572, "text": "ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1466, "text": "This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 880, "text": "The multiple cleavage sites on the R-loop substrate match the priming sites observed in vivo, suggesting that RNase MRP alone is capable of generating virtually all of the leading-strand replication primers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9119223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Mechanisms of primer RNA synthesis and D-loop/R-loop-dependent DNA replication in Escherichia coli.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9150892", "endSection": "title" }, { "offsetInBeginSection": 582, "offsetInEndSection": 773, "text": "Alternative oriC-independent modes of replication initiation are possible, one of which is constitutive stable DNA replication (cSDR) from transcription-associated RNA-DNA hybrids or R-loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25569209", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 601, "text": "Our results suggest that Top1 execute this function by suppressing the formation of DNA-RNA hybrids during transcription, these so-called R-loops interfering with the progression of replication forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20495385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Critical role of R-loops in processing replication blocks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15569610", "endSection": "title" }, { "offsetInBeginSection": 794, "offsetInEndSection": 986, "text": "The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9009281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19841062", "endSection": "title" }, { "offsetInBeginSection": 453, "offsetInEndSection": 621, "text": "More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979917", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 517, "text": "Consistent with this hypothesis, the 3' ends of the mitochondrial R-loop formed by in vitro transcription are located close to the initiation sites of the mitochondrial DNA replication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10082645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22965135", "endSection": "title" }, { "offsetInBeginSection": 414, "offsetInEndSection": 583, "text": "Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22965135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7774596", "endSection": "abstract" } ] }, { "body": "Which two catechol-O-methyl transferase (COMT) inhibitors can be used for treatment of Parkinson disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19198095", "http://www.ncbi.nlm.nih.gov/pubmed/10733264", "http://www.ncbi.nlm.nih.gov/pubmed/11147512", "http://www.ncbi.nlm.nih.gov/pubmed/11147511", "http://www.ncbi.nlm.nih.gov/pubmed/12588639", "http://www.ncbi.nlm.nih.gov/pubmed/21164341", "http://www.ncbi.nlm.nih.gov/pubmed/19589043", "http://www.ncbi.nlm.nih.gov/pubmed/15372589", "http://www.ncbi.nlm.nih.gov/pubmed/12952501", "http://www.ncbi.nlm.nih.gov/pubmed/8784230", "http://www.ncbi.nlm.nih.gov/pubmed/1933685", "http://www.ncbi.nlm.nih.gov/pubmed/14741081", "http://www.ncbi.nlm.nih.gov/pubmed/10651109", "http://www.ncbi.nlm.nih.gov/pubmed/15853578" ], "ideal_answer": [ "Tolcapone (central and peripheral) and entacapone (peripheral) are catechol-O-methyl transferase inhibitors that are used for treatment of Parkinson disease." ], "exact_answer": [ [ "tolcapone" ], [ "entacapone" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300", "http://www.uniprot.org/uniprot/COMT_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016206", "http://www.uniprot.org/uniprot/COMT_RAT", "http://www.uniprot.org/uniprot/COMT_MOUSE", "http://www.uniprot.org/uniprot/COMT_HORSE", "http://www.uniprot.org/uniprot/COMT_BOVIN", "http://www.disease-ontology.org/api/metadata/DOID:14330", "http://www.uniprot.org/uniprot/COMT_PIG" ], "type": "list", "id": "51487ef9d24251bc05000031", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 215, "text": "Entacapone is a highly potent, reversible, peripherally acting catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to L-dopa in the treatment of patients with Parkinson disease (PD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21164341", "endSection": "sections.0" }, { "offsetInBeginSection": 1251, "offsetInEndSection": 1614, "text": "Stalevo is a combination tablet comprised of levodopa, carbidopa, and the COMT inhibitor entacapone. It is available in fixed-dose combinations of levodopa/carbidopa/entacapone, 50/12.5/200, 75/18.75/200, 100/25/200, 125/31.25/200, 150/37.5/200 and 200/50/200 mg. Stalevo is currently approved for use in Parkinson's disease patients with end-of-dose wearing off.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19589043", "endSection": "sections.0" }, { "offsetInBeginSection": 306, "offsetInEndSection": 637, "text": "Good news were marketing of ropinirole, a new non-ergot agonist, in December 2006 and entacapone, the first catechol-O-methyl transferase (COMT) inhibitor in Japan in April 2007. Having faced these new situations, Japanese Neurological Association has started revising \"the Guideline 2002 for the treatment of Parkinson's disease\".", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19198095", "endSection": "sections.0" }, { "offsetInBeginSection": 620, "offsetInEndSection": 776, "text": "Stalevo (Orion) combines levodopa, the dopa-decarboxylase inhibitor carbidopa and the catechol-O-methyl transferase inhibitor entacapone in a single tablet.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15853578", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "We investigated whether administration of the catechol-O-methyl transferase (COMT) inhibitor entacapone, at doses of 200 mg and 400 mg, alters the pharmacokinetics of apomorphine in Parkinson's disease patients experiencing severe motor fluctuations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15372589", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The catechol-O-methyl transferase inhibitor entacapone is given in combination with levodopa/dopa decarboxylase inhibitor for Parkinson's disease (PD) patients experiencing end-of-dose wearing-off.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14741081", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Entacapone (Comtess/Comtan) is Orion Pharma's original proprietary catechol-O-methyl transferase (COMT) inhibitor. Entacapone is able to slow down degradation of levodopa and improve the availability and efficacy of each levodopa dose, hence its use as a complement to levodopa/carbidopa in patients with Parkinson's disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12952501", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Sleep attacks in Parkinson's disease induced by Entacapone, a COMT-inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12588639", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "We present a patient who suffered from sleep attacks after starting entacapone in addition to levodopa. Entacapone, a catechol-O-methyl transferase inhibitor, alters the pharmacokinetics of levodopa, leading to increase of levodopa concentration in plasma and brain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12588639", "endSection": "sections.0" }, { "offsetInBeginSection": 160, "offsetInEndSection": 273, "text": "Two COMT inhibitors, tolcapone and entacapone, have recently been made available as adjunctive agents to levodopa", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11147512", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Two inhibitors of catechol-O-methyl transferase (COMT), tolcapone and entacapone, have recently been introduced as adjuncts to levodopa in the treatment of Parkinson's disease patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11147511", "endSection": "sections.0" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1569, "text": "Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, producing a 47% reduction in 'off' time.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10733264", "endSection": "sections.0" }, { "offsetInBeginSection": 1761, "offsetInEndSection": 1957, "text": ". Entacapone, a purely peripheral COMT inhibitor with a lower potency than tolcapone, has also proved to be effective and has not been associated with liver damage, obviating the need for testing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10733264", "endSection": "sections.0" }, { "offsetInBeginSection": 316, "offsetInEndSection": 524, "text": "Here we report that a treatment of the cerebral tissue with tolcapone, a central and peripheral inhibitor of COMT, does not change the membrane responses of midbrain dopamine neurons to dopamine and levodopa.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10651109", "endSection": "sections.0" }, { "offsetInBeginSection": 721, "offsetInEndSection": 873, "text": "Therefore, the therapeutic action of tolcapone in Parkinson's disease, might be dependent on the reduction of COMT activity in the extracerebral tissue.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10651109", "endSection": "sections.0" }, { "offsetInBeginSection": 294, "offsetInEndSection": 568, "text": "Pretreatment with entacapone (OR-611), a peripheral catechol O-methyl-transferase (COMT) inhibitor, greatly reduces the plasma 3OMFD fraction and provides an ideal situation to evaluate the contribution of the plasma 3OMFD fraction in several kinetic models of FDOPA uptake.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8784230", "endSection": "sections.0" }, { "offsetInBeginSection": 87, "offsetInEndSection": 356, "text": "The novel and reversible inhibitors are the catechol-O-methyl-transferase (COMT) inhibitors, Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), and the monoamine oxidase type-B (MAO-B) inhibitor, Ro 19-6327 (N-(2-aminoethyl)-5-chloro-2-pyridine carboxamide HC1).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1933685", "endSection": "sections.0" } ] }, { "body": "What are the structures formed when keratin molecules come together?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22502568", "http://www.ncbi.nlm.nih.gov/pubmed/21721843", "http://www.ncbi.nlm.nih.gov/pubmed/22585043", "http://www.ncbi.nlm.nih.gov/pubmed/23396250", "http://www.ncbi.nlm.nih.gov/pubmed/22963508", "http://www.ncbi.nlm.nih.gov/pubmed/22168818", "http://www.ncbi.nlm.nih.gov/pubmed/21945137", "http://www.ncbi.nlm.nih.gov/pubmed/23331681", "http://www.ncbi.nlm.nih.gov/pubmed/22238362", "http://www.ncbi.nlm.nih.gov/pubmed/22250786", "http://www.ncbi.nlm.nih.gov/pubmed/21844209", "http://www.ncbi.nlm.nih.gov/pubmed/22507538" ], "ideal_answer": [ "Keratins form the intermediate filaments of the cytoskeleton and provide scaffold structures within cells." ], "exact_answer": [ "Intermediate filaments" ], "concepts": [ "http://www.biosemantics.org/jochem#4249492", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000595", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007633", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017434", "http://www.uniprot.org/uniprot/KRT_CEREL", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017433" ], "type": "factoid", "id": "5505db6a8e1671127b000003", "snippets": [ { "offsetInBeginSection": 512, "offsetInEndSection": 619, "text": " Keratins form the intermediate filaments of the cytoskeleton and provide scaffold structures within cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23396250", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 59, "text": "keratin intermediate filaments", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23396250", "endSection": "title" }, { "offsetInBeginSection": 612, "offsetInEndSection": 642, "text": "keratin intermediate filaments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23331681", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 94, "text": "keratin intermediate filament protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963508", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Keratin is a protein in the intermediate filament family ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963508", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 571, "text": "Keratins are the intermediate filament (IF) proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22585043", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 658, "text": "squamous keratinocytes contain polymerized keratin intermediate filament bundles ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22507538", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 470, "text": " keratin filaments ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22502568", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 506, "text": " In this study, we have examined the distribution of four groups of IFs [cytokeratins (CKs), vimentin, desmin and lamins]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22250786", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 571, "text": "keratin filament network", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22238362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "An intact keratin 5/keratin 14 intermediate filament cytoskeleton is vital for the integrity of basal keratinocytes and for the development and maintenance of epidermal structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22168818", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 903, "text": "keratin intermediate filament cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21945137", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 864, "text": "keratin filaments,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21844209", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1148, "text": "keratin filamentous network. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21721843", "endSection": "abstract" } ] }, { "body": "Which is the prognostic impact of hypothyroidism in patients with acute myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16330914", "http://www.ncbi.nlm.nih.gov/pubmed/19609889", "http://www.ncbi.nlm.nih.gov/pubmed/11747849", "http://www.ncbi.nlm.nih.gov/pubmed/23124142", "http://www.ncbi.nlm.nih.gov/pubmed/23990180" ], "ideal_answer": [ "Thyroid dysfunction, particularly low T3 syndrome, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions." ], "exact_answer": [ "Low T3 Syndrome isassociatedwithpoor prognosis in patients with acute myocardial infarction" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056989", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.disease-ontology.org/api/metadata/DOID:5844", "http://www.disease-ontology.org/api/metadata/DOID:1459", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007037", "http://www.disease-ontology.org/api/metadata/DOID:9408" ], "type": "factoid", "id": "531d1998267d7dd053000001", "snippets": [ { "offsetInBeginSection": 1073, "offsetInEndSection": 1258, "text": "In-hospital cardiogenic shock (15% vs 3% in the control group; p<0.01) and death (7% vs 1% in the control group; p<0.01) were more frequently observed in the thyroid dysfunction group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990180", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1633, "text": "Thyroid dysfunction, particularly sick euthyroid syndrome, was found to be related to in-hospital and long term mortality in patients with STEMI undergoing primary percutaneous intervention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990180", "endSection": "abstract" }, { "offsetInBeginSection": 1387, "offsetInEndSection": 1582, "text": "A low fT3 level, a common phenomenon in patients with acute myocardial infarctions, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124142", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1149, "text": "Troponin T and creatine kinase-B with an M-type subunit levels were significantly higher in the nonsurvivors when compared with survivors. Survivors in the AMI group had higher TT3, TT4, and lower FT4 levels, while the nonsurvivors in the AMI group had higher thyrotrophin and lower TT3, FT3 and FT4 levels than controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16330914", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1530, "text": "Reverse T3 levels >0.41 nmol/L were associated with an increased risk of 1-year mortality (hazard ratio = 3.0; 95% confidence interval: 1.4 to 6.3; P = 0.005), independent of age, previous myocardial infarction, prior angina, heart failure, serum creatinine level, and peak serum creatine kinase-MB fraction levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11747849", "endSection": "abstract" } ] }, { "body": "Which are the main features of CREST and other ALS-linked proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/13129802", "http://www.ncbi.nlm.nih.gov/pubmed/25173930", "http://www.ncbi.nlm.nih.gov/pubmed/24360741", "http://www.ncbi.nlm.nih.gov/pubmed/16808883", "http://www.ncbi.nlm.nih.gov/pubmed/24115583", "http://www.ncbi.nlm.nih.gov/pubmed/24355598", "http://www.ncbi.nlm.nih.gov/pubmed/24920614", "http://www.ncbi.nlm.nih.gov/pubmed/25888396" ], "ideal_answer": [ "CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.", "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles. Like several other ALS-associated proteins, CREST is recruited to induced stress granules. Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.", "Like several other ALS-associated proteins, CREST is recruited to induced stress granules. " ], "type": "summary", "id": "56c9f9d95795f9a73e00001e", "snippets": [ { "offsetInBeginSection": 115, "offsetInEndSection": 248, "text": "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 624, "text": "Like several other ALS-associated proteins, CREST is recruited to induced stress granules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1453, "text": "CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 247, "text": "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 623, "text": " Like several other ALS-associated proteins, CREST is recruited to induced stress granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1453, "text": "Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 235, "text": "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1571, "text": "Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity. A change in CREST levels in neurons which might occur under pathological conditions would have a profound negative effect on neuronal homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Calcium-responsive transactivator (CREST) protein shares a set of structural and functional traits with other proteins associated with amyotrophic lateral sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "title" }, { "offsetInBeginSection": 25, "offsetInEndSection": 114, "text": "calcium-responsive transactivator (CREST) encoding gene have been recently linked to ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25888396", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 373, "text": "A de novo mutation in the SS18L1 (also known as CREST or KIAA0693) gene encoding the calcium-responsive transactivator and/or neuronal chromatin remodeling complex subunit has recently been identified by exome sequencing of 47 sporadic ALS trios.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24360741", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1529, "text": "Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24920614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25173930", "endSection": "title" }, { "offsetInBeginSection": 374, "offsetInEndSection": 501, "text": "In the present study, we examined the effects of ALS-linked FUS mutants on ALS-associated RNA binding proteins and RNA granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25173930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25173930", "endSection": "title" } ] }, { "body": "Mutations of which genes have been associated with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20301466", "http://www.ncbi.nlm.nih.gov/pubmed/22422768", "http://www.ncbi.nlm.nih.gov/pubmed/24370574", "http://www.ncbi.nlm.nih.gov/pubmed/23595086", "http://www.ncbi.nlm.nih.gov/pubmed/20807279", "http://www.ncbi.nlm.nih.gov/pubmed/22787013", "http://www.ncbi.nlm.nih.gov/pubmed/22589293", "http://www.ncbi.nlm.nih.gov/pubmed/16601229", "http://www.ncbi.nlm.nih.gov/pubmed/25480325", "http://www.ncbi.nlm.nih.gov/pubmed/23908839" ], "ideal_answer": [ "Mutations in five genes \u2013 ryanodine receptor 2 (RYR2), calsequestrin 2(CASQ2), triadic (TRDN), calmodulin 1 (CALM1) and potassium channel, inwardly rectifying subfamily J, member 2 (KCNJ2) \u2013 have been found to be associated with CPVT" ], "exact_answer": [ [ "ryanodine receptor 2", "RYR2" ], [ "calsequestrin 2", "CASQ2" ], [ "triadin", "TRDN" ], [ "calmodulin 1", "CALM1" ], [ "potassium channel, inwardly rectifying subfamily J, member 2", "KCNJ2" ] ], "type": "list", "id": "54c225bcf693c3b16b000002", "snippets": [ { "offsetInBeginSection": 1703, "offsetInEndSection": 1921, "text": "Mutation in four genes \u2013 RYR2, CASQ2, TRDN, and CALM1 \u2013 is known to cause CPVT or related phenotypes of adrenergically induced life-threatening arrhythmias. The presence of other as-yet unidentified loci is postulated ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301466", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 384, "text": "some KCNJ2 mutation carriers lack the ATS triad and sometimes share the phenotype of catecholaminergic polymorphic ventricular tachycardia (CPVT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589293", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 513, "text": "In 50 Japanese probands from unrelated families who satisfied clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23595086", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 947, "text": "point mutations in RYR2, the gene encoding for the cardiac isoform of the RyR (RyR2), are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), an arrhythmogenic syndrome characterized by the development of adrenergically-mediated ventricular tachycardia in individuals with an apparently normal heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25480325", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 528, "text": "Recessive CPVT variants are due to mutations in the CASQ2 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24370574", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 507, "text": "Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23908839", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 817, "text": "We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22422768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmogenic disorder associated with mutations in the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16601229", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22422768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787013", "endSection": "abstract" } ] }, { "body": "What is the relationship between nucleosomes and exons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20808788", "http://www.ncbi.nlm.nih.gov/pubmed/15862762", "http://www.ncbi.nlm.nih.gov/pubmed/21289049", "http://www.ncbi.nlm.nih.gov/pubmed/19687145", "http://www.ncbi.nlm.nih.gov/pubmed/19684599", "http://www.ncbi.nlm.nih.gov/pubmed/20097656", "http://www.ncbi.nlm.nih.gov/pubmed/21859475", "http://www.ncbi.nlm.nih.gov/pubmed/22683623", "http://www.ncbi.nlm.nih.gov/pubmed/22954214", "http://www.ncbi.nlm.nih.gov/pubmed/19823040", "http://www.ncbi.nlm.nih.gov/pubmed/8918932", "http://www.ncbi.nlm.nih.gov/pubmed/9461388", "http://www.ncbi.nlm.nih.gov/pubmed/11724736" ], "ideal_answer": [ "Nucleosomes are preferentially located within exons compared to nearby intronic sequences. Preferential positioning within the exons is indepedent of gene expression levels, stronger in exons with weak splice sites and conserved through metazoan evolution." ], "type": "summary", "id": "5173a8b48ed59a060a00001d", "snippets": [ { "offsetInBeginSection": 372, "offsetInEndSection": 557, "text": "Nucleosomes preferentially are located at the ends of exons, thus protecting splice junctions, with the N9 positions of guanines of the GT and AG junctions oriented toward the histones.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22954214", "endSection": "sections.0" }, { "offsetInBeginSection": 397, "offsetInEndSection": 691, "text": "Nucleosomes were found to be preferentially positioned within constitutive exons and/or constitutive portions of alternative exons, which was not associated with gene expression or states of cells but was based on sequence and positively related with the sequence conservation of splicing sites", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683623", "endSection": "sections.0" }, { "offsetInBeginSection": 375, "offsetInEndSection": 632, "text": "Here, we discuss the evidence supporting these ideas, from the first proposal of chromatin affecting alternative splicing, performed 20 years ago, to the latest findings including genome-wide evidence that nucleosomes are preferentially positioned in exons.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21289049", "endSection": "sections.0" }, { "offsetInBeginSection": 545, "offsetInEndSection": 814, "text": "Here we show, by analysis of data sets from human sperm and T cells and medaka (Japanese killifish, Oryzias latipes) blastulae, that internal exons of genes are characterized by sharply elevated average nucleosome occupancy in comparison to flanking intronic sequences.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19823040", "endSection": "sections.0" }, { "offsetInBeginSection": 376, "offsetInEndSection": 645, "text": "sing public data, we here show that there is a higher nucleosome-positioning signal in internal human exons and that this positioning is independent of expression. We observed a similarly strong nucleosome-positioning signal in internal exons of Caenorhabditis elegans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19687145", "endSection": "sections.0" }, { "offsetInBeginSection": 234, "offsetInEndSection": 371, "text": "we have found stable nucleosome occupancy within human and Caenorhabditis elegans exons that is stronger in exons with weak splice sites.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19684599", "endSection": "sections.0" }, { "offsetInBeginSection": 172, "offsetInEndSection": 289, "text": "This confirms previously reported findings about preferential positioning of splice junctions within the nucleosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15862762", "endSection": "sections.0" } ] }, { "body": "List programs suitable for pharmacophore modelling", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20499259", "http://www.ncbi.nlm.nih.gov/pubmed/20045317", "http://www.ncbi.nlm.nih.gov/pubmed/22272142", "http://www.ncbi.nlm.nih.gov/pubmed/22779800", "http://www.ncbi.nlm.nih.gov/pubmed/19691298", "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "http://www.ncbi.nlm.nih.gov/pubmed/22553386", "http://www.ncbi.nlm.nih.gov/pubmed/21955456", "http://www.ncbi.nlm.nih.gov/pubmed/18763758", "http://www.ncbi.nlm.nih.gov/pubmed/23202316", "http://www.ncbi.nlm.nih.gov/pubmed/21342558", "http://www.ncbi.nlm.nih.gov/pubmed/21138791", "http://www.ncbi.nlm.nih.gov/pubmed/20055175", "http://www.ncbi.nlm.nih.gov/pubmed/21179343", "http://www.ncbi.nlm.nih.gov/pubmed/22435086", "http://www.ncbi.nlm.nih.gov/pubmed/17477520", "http://www.ncbi.nlm.nih.gov/pubmed/20116902", "http://www.ncbi.nlm.nih.gov/pubmed/22587766", "http://www.ncbi.nlm.nih.gov/pubmed/9651155", "http://www.ncbi.nlm.nih.gov/pubmed/21143043", "http://www.ncbi.nlm.nih.gov/pubmed/20621485", "http://www.ncbi.nlm.nih.gov/pubmed/20427100", "http://www.ncbi.nlm.nih.gov/pubmed/21284830", "http://www.ncbi.nlm.nih.gov/pubmed/17668276", "http://www.ncbi.nlm.nih.gov/pubmed/20085380", "http://www.ncbi.nlm.nih.gov/pubmed/22546667" ], "ideal_answer": [ "A pharmacophore is an abstract description of molecular features which are necessary for molecular recognition of a ligand by a biological macromolecule. The IUPAC defines a pharmacophore to be \"an ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response\". A pharmacophore model explains how structurally diverse ligands can bind to a common receptor site. Furthermore pharmacophore models can be used to identify through denovo design or virtual screening novel ligands that will bind to the same receptor. Nowadays there are many programs suitable for pharmacophore modelling such as LigandScout, Discovery Studio, Catalyst, PharmaGist, Genetic Algorithm Similarity and Molecular Operating Environment." ], "exact_answer": [ [ "LigandScout program" ], [ "Discovery Studio program", "3D QSAR Pharmacophore Generation module" ], [ "Catalyst", "HipHop module", "HypoGen module" ], [ "PharmaGist" ], [ "Genetic Algorithm Similarity Program (GASP)" ], [ "Molecular Operating Environment (MOE)", "Pharmacophore Elucidation" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003198", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015195", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019542" ], "type": "list", "id": "532c0d7fd6d3ac6a3400001c", "snippets": [ { "offsetInBeginSection": 138, "offsetInEndSection": 260, "text": "Pharmacophore models based on thermolysin binding modes and activity profiles were generated using the LigandScout program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22587766", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 318, "text": "In this study, pharmacophore hypotheses based on known inhibitors were generated using common feature pharmacophore generation protocol available in Discovery Studio program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21143043", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1163, "text": " A pharmacophore-based screening was then carried out using the program Catalyst", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17668276", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1633, "text": "The PharmaGist employed algorithm to identify the best pharmacophores by computing multiple flexible alignments between the input ligands. The multiple alignments are generated by combining alignments pair-wise between one of the gliptin input ligands, which acts as pivot and the other gliptin as ligand. The resulting multiple alignments reveal spatial arrangements of consensus features shared by different subsets of input ligands. The best pharmacophore model has been derived using both pair-wise and multiple alignment methods, which have been weighted in Pharmacophore Generation process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23140189", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 325, "text": "Pharmacophore models of c-Met kinase inhibitors have been developed based on 22 diverse compounds by using HypoGen algorithm implemented in Discovery studio program package.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22779800", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 179, "text": "chemical feature based pharmacophore models of MMP-1, MMP-8 and MMP-13 inhibitors have been developed with the aid of HypoGen module within Catalyst program package", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553386", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 458, "text": "Genetic Algorithm Similarity Program (GASP) was used to derive a 3D pharmacophore model which was used in effective alignment of data set.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22546667", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1255, "text": "Active site complimenting structure-based pharmacophore models were developed using Discovery Studio 2.5 program and validated using a dataset of known HDAC8 inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272142", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1438, "text": " pharmacophore model has been generated from the training set by means of the MOE (molecular operating environment) program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21955456", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1169, "text": "A training set of 20 compounds with known experimental activity was used to generate pharmacophore hypotheses using 3D QSAR Pharmacophore Generation module available in Discovery studio. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21342558", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 664, "text": "Pharmacophore model was developed for the first time, on a training data set of 22 CCR3 antagonists, using CATALYST HypoRefine program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21284830", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 394, "text": "The CatalystHipHop approach was used to generate a pharmacophore model for cyclooxygenase-2 (COX-2) inhibitors based on a training set of 15 active inhibitors (1\u00e215). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21179343", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 305, "text": " Molecular modeling study, including fitting to a 3D-pharmacophore model of the designed molecules (10a-g), with HCV NS3 protease hypothesis using catalyst program was fulfilled.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21138791", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 135, "text": "pharmacophore model (Hypo1) with a well prediction capacity for CysLT(1) antagonists was developed using Catalyst/HypoGen program. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20621485", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 317, "text": "Three pharmacophore models of opioid agonists were generated by the Catalyst/HypoGen program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20499259", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 328, "text": "The superposition of the ligands was performed with the tool Pharmacophore Elucidation (MOE-package", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20427100", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 738, "text": "Known PDE-5 inhibitors were used to construct a three dimensional quantitative structure-activity relationship (3D QSAR) model by HypoGen program. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20085380", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 167, "text": "pharmacophore models were generated for AT1 and ET(A) receptors based on highly selective AT1 and ET(A) antagonists using the program Catalyst/HipHop", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20055175", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 309, "text": " In this study, chemical feature based pharmacophore models of inhibitors of 5-LOX have been developed with the aid of HipHop and HypoGen modules within Catalyst program package", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20045317", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 303, "text": "A data set consisting of 24 inhibitors was selected on the basis of the information content of the structures and activity data as required by the Catalyst/HypoGen program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19691298", "endSection": "abstract" } ] }, { "body": "Is selenium deficiency involved in autoimmune thyroid disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15132715", "http://www.ncbi.nlm.nih.gov/pubmed/22009156", "http://www.ncbi.nlm.nih.gov/pubmed/20810577", "http://www.ncbi.nlm.nih.gov/pubmed/21896670", "http://www.ncbi.nlm.nih.gov/pubmed/23448365", "http://www.ncbi.nlm.nih.gov/pubmed/19034261", "http://www.ncbi.nlm.nih.gov/pubmed/11932302", "http://www.ncbi.nlm.nih.gov/pubmed/17160166", "http://www.ncbi.nlm.nih.gov/pubmed/23565426", "http://www.ncbi.nlm.nih.gov/pubmed/23786024" ], "ideal_answer": [ "Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interactionIn areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells", "The essential trace element selenium was recently recognized as being incorporated as selenocysteine in all three deiodinases of the thyroid gland. This has decisively confirmed the clear-cut link between selenium and thyroid function. Additionally, it has been established that the thyroid contains more selenium than any other tissue, and that selenium deficiency aggravates the manifestation of autoimmune thyroid disease.", "The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease " ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013967", "http://www.biosemantics.org/jochem#4278041", "http://www.disease-ontology.org/api/metadata/DOID:7188" ], "type": "yesno", "id": "550c1ca3a103b78016000003", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 205, "text": "In areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565426", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1355, "text": "Of 30 patients in the selenium treated group, 6 patients were overtly hypothyroid, 15 were subclinical hypothyroid, 6 were euthyroid, and 3 were subclinical hyperthyroid. The mean TPOAb concentration decreased significantly by 49.5% (P < 0.013) in the selenium treated group versus 10.1% (P < 0.95) in the placebo-treated group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565426", "endSection": "abstract" }, { "offsetInBeginSection": 1369, "offsetInEndSection": 1479, "text": "Selenium substitution has a significant impact on inflammatory activity in thyroid-specific autoimmune disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Serum selenium is low in newly diagnosed Graves' disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365", "endSection": "title" }, { "offsetInBeginSection": 678, "offsetInEndSection": 801, "text": "S-Se was lower in patients with GD than in controls (mean (SD), GD: 89\u00b79\u00a0\u03bcg/l (18\u00b74); controls: 98\u00b78\u00a0\u03bcg/l (19\u00b77), P\u00a0<\u00a00\u00b701)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365", "endSection": "abstract" }, { "offsetInBeginSection": 1371, "offsetInEndSection": 1603, "text": "Patients with newly diagnosed GD and AIH had significantly lower s-Se compared with random controls. Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1852, "text": "Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 437, "text": "The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577", "endSection": "abstract" }, { "offsetInBeginSection": 1669, "offsetInEndSection": 1834, "text": "Maintenance of \"selenostasis\" via optimal intake not only aids preservation of general health but also contributes substantially to the prevention of thyroid disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 844, "text": "Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15132715", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 428, "text": "It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Selenium deficiency may play an important role in the initiation and progression of autoimmune thyroid disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "[Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19034261", "endSection": "title" }, { "offsetInBeginSection": 516, "offsetInEndSection": 842, "text": "Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15132715", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1304, "text": "Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1489, "text": "Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448365", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 77, "text": "Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19034261", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896670", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 438, "text": "It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1222, "text": "EVIDENCE SYNTHESIS: Evidence in support of selenium supplementation in thyroid autoimmune disease is evaluated, the results herein presented demonstrating the potential effectiveness of selenium in reducing the antithyroid peroxidase titer and improving the echostructure in the ultrasound examination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1288, "text": "Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17160166", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 395, "text": "Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11932302", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1311, "text": "Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1309, "text": "Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "High prevalence of hyperplastic and autoimmune diseases of thyroid in Ukrainian population is determined by endemic deficit of iodine and selenium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23786024", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 429, "text": "It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810577", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 394, "text": "Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11932302", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1287, "text": "Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17160166", "endSection": "abstract" } ] }, { "body": "List disorders that are caused by mutations in the mitochondrial MTND6 gene.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24126373", "http://www.ncbi.nlm.nih.gov/pubmed/16885236", "http://www.ncbi.nlm.nih.gov/pubmed/8090716", "http://www.ncbi.nlm.nih.gov/pubmed/7654063", "http://www.ncbi.nlm.nih.gov/pubmed/22970697", "http://www.ncbi.nlm.nih.gov/pubmed/16044424", "http://www.ncbi.nlm.nih.gov/pubmed/23847141" ], "ideal_answer": [ "Mitochondrial MTND6 gene mutations are the cause of Leigh syndrome and Leber's hereditary optic neuropathy and/or dystonia." ], "exact_answer": [ [ "Leigh syndrome" ], [ "Leber's hereditary optic neuropathy and/or dystonia" ] ], "concepts": [ "http://www.uniprot.org/uniprot/NU6M_GADMO" ], "type": "list", "id": "530c844e970c65fa6b000014", "snippets": [ { "offsetInBeginSection": 1216, "offsetInEndSection": 1364, "text": "It was shown that m14487T>C can also cause the unusual combination of optic atrophy, ptosis, and encephalomyopathy leading to intractable seizures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24126373", "endSection": "abstract" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1426, "text": " MTND6 genes were identified as 'hotspots' of mutations, with Leigh syndrome accounting for the large majority of associated phenotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23847141", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 538, "text": "he 14487T>C mutation in MTND6 were present in two probands with Leigh's-like and Leigh's syndrome, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16044424", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1214, "text": "These results confirm the association of the MTND6*LDYT14459A mutation with Leber's hereditary optic neuropathy and/or dystonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7654063", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "A novel point mutation in the ND6 subunit of complex I at position 14,459 of the mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for the highly tissue-specific disease. Leber's hereditary optic neuropathy plus dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7654063", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1139, "text": "Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090716", "endSection": "abstract" } ] }, { "body": "Which are the most common methods for ctDNA (circulating tumour DNA) detection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25220802", "http://www.ncbi.nlm.nih.gov/pubmed/26539452", "http://www.ncbi.nlm.nih.gov/pubmed/24705333", "http://www.ncbi.nlm.nih.gov/pubmed/25489581", "http://www.ncbi.nlm.nih.gov/pubmed/20970979" ], "ideal_answer": [ "Recently, nanoplasmonics has emerged as a platform for one-step dual detection with high sensitivity and specificity. The practice of \"liquid biopsy\" as a diagnostic, prognostic and theranostic tool in non-small cell lung cancer (NSCLC) patients is an appealing approach, at least in theory, since it is noninvasive and easily repeated. Cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. A new DNA sensor using a nickel(II) phenanthroline complex ([Ni(phen)(2)PHPIP]\u00b72ClO(4)) as the electrochemical probe was developed. The sensor is very sensitive and selective for calf thymus DNA (ctDNA) detection in aqueous medium.", "A new DNA sensor using a nickel(II) phenanthroline complex ([Ni(phen)(2)PHPIP]\u00b72ClO(4)) as the electrochemical probe was developed. The calculated dynamics parameters of the electrode process indicate that there are obvious interactions between the probe and the ctDNA in aqueous solution. Under constant potential conditions, the redox current peak of the probe (Ni-complex) decreases obviously as the probe interacts/binds with ctDNAs. These results demonstrate that the sensor can simultaneously detect the hot-spot mutation and epigenetic changes on the ctDNA." ], "exact_answer": [ [ "nanoplasmonics", "biosensors" ], [ "liquid biopsy" ], [ "Cancer personalized profiling by deep sequencing", "CAPP-Seq" ], [ "electrochemical sensors" ] ], "type": "list", "id": "571653aecb4ef8864c000005", "snippets": [ { "offsetInBeginSection": 147, "offsetInEndSection": 220, "text": "existing methods for ctDNA detection are restricted to genetic mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25220802", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 338, "text": "Recently, nanoplasmonics has emerged as a platform for one-step dual detection with high sensitivity and specificity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25220802", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1498, "text": "These results demonstrate that the sensor can simultaneously detect the hot-spot mutation and epigenetic changes on the ctDNA. Promisingly, other specific-tumor mutants and epigenetic changes can be detected at low concentration with this platform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25220802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The practice of \"liquid biopsy\" as a diagnostic, prognostic and theranostic tool in non-small cell lung cancer (NSCLC) patients is an appealing approach, at least in theory, since it is noninvasive and easily repeated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25489581", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 363, "text": "Here we introduce cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705333", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1171, "text": "Finally, we evaluated biopsy-free tumor screening and genotyping with CAPP-Seq. We envision that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalized cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Synthesis of a new Ni-phenanthroline complex and its application as an electrochemical probe for detection of nucleic acid", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20970979", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "A new DNA sensor using a nickel(II) phenanthroline complex ([Ni(phen)(2)PHPIP]\u00b72ClO(4)) as the electrochemical probe was developed. The sensor is very sensitive and selective for calf thymus DNA (ctDNA) detection in aqueous medium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20970979", "endSection": "abstract" } ] }, { "body": "Which gene is associated with Muenke syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15241680", "http://www.ncbi.nlm.nih.gov/pubmed/17036334", "http://www.ncbi.nlm.nih.gov/pubmed/19449410", "http://www.ncbi.nlm.nih.gov/pubmed/17103449", "http://www.ncbi.nlm.nih.gov/pubmed/12794698", "http://www.ncbi.nlm.nih.gov/pubmed/19215249", "http://www.ncbi.nlm.nih.gov/pubmed/17414289", "http://www.ncbi.nlm.nih.gov/pubmed/22622662", "http://www.ncbi.nlm.nih.gov/pubmed/19755431", "http://www.ncbi.nlm.nih.gov/pubmed/24168007", "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "http://www.ncbi.nlm.nih.gov/pubmed/20592905", "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "http://www.ncbi.nlm.nih.gov/pubmed/14963686", "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "http://www.ncbi.nlm.nih.gov/pubmed/19086028", "http://www.ncbi.nlm.nih.gov/pubmed/23378035" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/FGFR3" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/FGFR3", "o": "FGFR3" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/FGFR3", "o": "http://www.dbpedia.org/resource/FGFR3" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "Muenke syndrome, 602849" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/779" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/779", "o": "Muenke_syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/779", "o": "http://www.dbpedia.org/resource/Muenke_syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11978039", "o": "OMIM" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11978039" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11978039", "o": "MUENKE SYNDROME, PRO250ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11978039" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11992529", "o": "FGFR3, PRO250ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851163", "o": "http://linkedlifedata.com/resource/umls/label/A11992529" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11992529", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11978039", "o": "134934.0014" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11992529", "o": "134934.0014" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_id", "s": "http://data.linkedct.org/resource/condition/8322", "o": "8322" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/condition/8322", "o": "Condition #8322 (Muenke Syndrome)" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_name", "s": "http://data.linkedct.org/resource/condition/8322", "o": "Muenke Syndrome" } ], "ideal_answer": [ "Muenke syndrome has been related to a mutation on the Fibroblast Growth Factor Receptor (FGFR3) gene." ], "exact_answer": [ "Fibroblast Growth Factor Receptor 3 (FGFR3)" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "factoid", "id": "52bf1d2e03868f1b0600000c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "Abstract Muenke is a fibroblast growth factor receptor 3 (FGFR-3) associated syndrome, which was first described in late 1990s. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24168007", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 475, "text": "The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24168007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 528, "text": "Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3(P250R) ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22622662", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 437, "text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 788, "text": "Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 807, "text": " Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19755431", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 407, "text": "We report on a set of identical twins with a de novo C749G mutation in the FGFR3 gene codon 250 after a pregnancy complicated by prenatal exposure to Nortriptyline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19449410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19215249", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 542, "text": "The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19215249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans. We have used gene targeting to introduce the Muenke syndrome mu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19086028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 579, "text": "To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 532, "text": "The patients were either placed into the \"Muenke\" group (n=11) or the \"non-Muenke\" control group (n=12) on the basis of a test for the P250R mutation in the FGFR3 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17414289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103449", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 279, "text": "However, Muenke et al. [(1997); Am J Hum Genet 91: 555-564] described a new subgroup carrying the Pro250Arg mutation in the fibroblast growth factor receptor (FGFR) 3 gene on chromosome 4p16.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17036334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15241680", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 487, "text": "In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14963686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12794698", "endSection": "abstract" } ] }, { "body": "Is it safe to use Abatacept during pregnancy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21120498", "http://www.ncbi.nlm.nih.gov/pubmed/21346578", "http://www.ncbi.nlm.nih.gov/pubmed/18504282", "http://www.ncbi.nlm.nih.gov/pubmed/23292481", "http://www.ncbi.nlm.nih.gov/pubmed/19506586", "http://www.ncbi.nlm.nih.gov/pubmed/18819772", "http://www.ncbi.nlm.nih.gov/pubmed/22772888", "http://www.ncbi.nlm.nih.gov/pubmed/21985166" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A15515315", "o": "308106" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2344752", "o": "http://linkedlifedata.com/resource/umls/label/A15515315" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15515315", "o": "ABATACEPT 50 MG" } ], "ideal_answer": [ "It is not safe to use the drug abatacept during pregnancy, since there is very limited experience/knowledge yet. Additionally, it is recommended to withdraw the drug before pregnancy.", "Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011248", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007565", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011256", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018566", "http://www.biosemantics.org/jochem#4002070", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060136" ], "type": "yesno", "id": "52bf1aa503868f1b06000006", "snippets": [ { "offsetInBeginSection": 480, "offsetInEndSection": 777, "text": "These patients were exposed to rituximab (anti-CD20 monoclonal antibody) or abatacept (fusion protein CTLA4Ig) during the first trimester of their pregnancies. No significant adverse effects or complications were observed during the pregnancies, and all three patients delivered healthy newborns. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23292481", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1214, "text": "Despite these favorable outcomes, the use of these two biological agents must follow international recommendations. Their use is not currently allowed during pregnancy except in cases where the potential benefit to the mother justifies the potential risk to the fetus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23292481", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1265, "text": "PREGNANCY: Azathioprine, chloroquine, cyclosporin A, prednisolone, sulfasalazine, tacrolimus and cyclophosphamide (only after the second trimester) may be administered during pregnancy. Biologics should be avoided unless there is a treatment need in cases of uncontrolled disease activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22772888", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1244, "text": "As such, it is recommended that abatacept, rituximab and tocilizumab be withheld prior to pregnancy; however, tumour necrosis factor inhibitors and anakinra may be continued until conception. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21985166", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 926, "text": "Case reports on abatacept, tocilizumab or anakinra in pregnancy are not conclusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21346578", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1333, "text": "The very limited experience with abatacept, tocilizumab or anakinra in pregnancy allows no statement as to their compatibility with pregnancy. At present use of biological agents throughout pregnancy cannot be recommended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21346578", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 642, "text": "Drugs recommended to be stopped before pregnancy include methotrexate and leflunomide, plus the biologics: anti-TNF agents, rituximab and abatacept.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21120498", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 641, "text": "Whereas methotrexate, leflunomide, abatacept and rituximab must be withdrawn before a planned pregnancy, tumor necrosis factor inhibitors and bisphosphonates can be continued until conception.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19506586", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 604, "text": "Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18504282", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 976, "text": "Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18504282", "endSection": "abstract" } ] }, { "body": "What is DeepCAGE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19074369", "http://www.ncbi.nlm.nih.gov/pubmed/20967606" ], "ideal_answer": [ "The cap analysis of gene expression (CAGE) technology has been established to detect transcriptional starting sites (TSSs) and expression levels by utilizing 5' cDNA tags and PCR. It has been reported that the amount of templates is proportional to the amplification efficiency of PCR. CAGE has been used as a key technique for analyzing promoter activity and finding new transcripts including alternative spliced products and noncoding transcripts. DeepCAGE can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network." ], "type": "summary", "id": "569e7e99ceceede94d000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 698, "text": "The cap analysis of gene expression (CAGE) technology has been established to detect transcriptional starting sites (TSSs) and expression levels by utilizing 5' cDNA tags and PCR. It has been reported that the amount of templates is proportional to the amplification efficiency of PCR. CAGE has been used as a key technique for analyzing promoter activity and finding new transcripts including alternative spliced products and noncoding transcripts. Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 497, "text": "Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 966, "text": "DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 804, "text": "DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1060, "text": "DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 721, "text": "Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 497, "text": "Mammalian cells have at least 5-10 magnitudes more TSS than previously believed, and deeper sequencing is necessary to detect all active promoters in a given tissue. Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 588, "text": "Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 967, "text": "Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074369", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 704, "text": "Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967606", "endSection": "abstract" } ] }, { "body": "Is STAT3 involved in EIF2AK2-dependent suppression of autophagy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "http://www.ncbi.nlm.nih.gov/pubmed/23084476" ], "ideal_answer": [ "STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy", "Pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. On the other hand, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy. Therefore, STAT3 may act as a competitive inhibitor of EIF2AK2 to suppress autophagy." ], "exact_answer": "yes", "type": "yesno", "id": "56cdf3995795f9a73e00003a", "snippets": [ { "offsetInBeginSection": 843, "offsetInEndSection": 1277, "text": "STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1527, "text": "Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1806, "text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1927, "offsetInEndSection": 2138, "text": "These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476", "endSection": "title" }, { "offsetInBeginSection": 371, "offsetInEndSection": 772, "text": "The SH2 domain of STAT3 was found to interact with the catalytic domain of the eIF2\u03b1 kinase 2 EIF2AK2, best known as protein kinase R (PKR). Pharmacological and genetic inhibition of STAT3 stimulated the activating phosphorylation of PKR and consequent eIF2\u03b1 hyperphosphorylation. Moreover, PKR depletion inhibited autophagy as initiated by chemical STAT3 inhibitors or free fatty acids like palmitate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 960, "text": "STAT3-targeting chemicals and palmitate caused the disruption of inhibitory STAT3-PKR interactions, followed by PKR-dependent eIF2\u03b1 phosphorylation, which facilitates autophagy induction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1133, "text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1917, "offsetInEndSection": 2255, "text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1925, "text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1016, "text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1277, "text": "However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "title" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1927, "text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1018, "text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "title" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1082, "text": "These results unravel an unsuspected mechanism of autophagy control that involves STAT3 and PKR as interacting partners.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084476", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1927, "text": "Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 2140, "text": "A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 1018, "text": "Thus, STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1187, "text": "Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1927, "text": ", Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23221979", "endSection": "abstract" } ] }, { "body": "RTS S AS01 vaccine was developed to prevent which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25913272", "http://www.ncbi.nlm.nih.gov/pubmed/25007730", "http://www.ncbi.nlm.nih.gov/pubmed/21782519", "http://www.ncbi.nlm.nih.gov/pubmed/24468190", "http://www.ncbi.nlm.nih.gov/pubmed/23787092", "http://www.ncbi.nlm.nih.gov/pubmed/25024381", "http://www.ncbi.nlm.nih.gov/pubmed/23454164", "http://www.ncbi.nlm.nih.gov/pubmed/21816030", "http://www.ncbi.nlm.nih.gov/pubmed/21816031", "http://www.ncbi.nlm.nih.gov/pubmed/22739688", "http://www.ncbi.nlm.nih.gov/pubmed/19806009", "http://www.ncbi.nlm.nih.gov/pubmed/21604980", "http://www.ncbi.nlm.nih.gov/pubmed/19859560", "http://www.ncbi.nlm.nih.gov/pubmed/21073995", "http://www.ncbi.nlm.nih.gov/pubmed/20735271", "http://www.ncbi.nlm.nih.gov/pubmed/21816032", "http://www.ncbi.nlm.nih.gov/pubmed/25077418", "http://www.ncbi.nlm.nih.gov/pubmed/24292709", "http://www.ncbi.nlm.nih.gov/pubmed/25072396" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "D004194" } ], "ideal_answer": [ "RTS,S/AS01 vaccine was developed for prevention of malaria." ], "exact_answer": [ "malaria" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014612", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194" ], "type": "factoid", "id": "56bc77a3ac7ad10019000015", "snippets": [ { "offsetInBeginSection": 188, "offsetInEndSection": 401, "text": "This randomized, double-blind study (NCT01323972) assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from commercial-scale purified antigen bulk lots in terms of anti-CS-responses induced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25077418", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 206, "text": "Until now, only one candidate malaria vaccine RTS,S/AS01 has shown modest protection in phase 3 trial in African infants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24468190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272", "endSection": "abstract" }, { "offsetInBeginSection": 3356, "offsetInEndSection": 3546, "text": "INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1376, "text": "WHO anticipates that the RTS,S/AS01 vaccine will be recommended for the 6-14 week age group for co-administration together with other vaccines as part of routine immunization programs in malaria endemic countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22739688", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 474, "text": "Recent phase 3 trials with malaria vaccine candidate RTS,S/AS01 (RTS,S) in children has demonstrated modest efficacy against clinical and severe malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292709", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 906, "text": "The RTS,S/AS01(E) malaria vaccine candidate has recently entered phase III testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23454164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816031", "endSection": "title" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1501, "text": "If the phase III results confirm the observations made during phase II testing, the RTS,S/AS01(E) vaccine, when broadly implemented and judiciously integrated with other malaria-prevention measures, would have a major public-health impact in sub-Saharan Africa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "The RTS,S/AS01(E) malaria vaccine candidate has recently entered Phase 3 testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19806009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The RTS,S/AS01(E) candidate malaria vaccine is being developed for immunisation of infants in Africa through the expanded programme on immunisation (EPI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21782519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20735271", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 327, "text": "Of the multiple approaches that have been pursued, the RTS,S/AS01 vaccine candidate represents the most developed and clinically validated malaria vaccine formulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21604980", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 338, "text": "AS01 has been selected for the clinical development of several candidate vaccines including the RTS,S malaria vaccine and the subunit glycoprotein E varicella zoster vaccine (both currently in phase III)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25024381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21782519", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19859560", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Effect of ingested human antibodies induced by RTS, S/AS01 malaria vaccination in children on Plasmodium falciparum oocyst formation and sporogony in mosquitoes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25007730", "endSection": "title" }, { "offsetInBeginSection": 3196, "offsetInEndSection": 3546, "text": "The incidence of generalised convulsive seizures within 7 days of RTS,S/AS01 booster was 2\ufffd2 per 1000 doses in young infants and 2\ufffd5 per 1000 doses in children.INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25913272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816032", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS, S/AS01 malaria vaccine in African children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816030", "endSection": "title" }, { "offsetInBeginSection": 1579, "offsetInEndSection": 1932, "text": "Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.CONCLUSIONS: RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25072396", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 1517, "text": "This article provides a summary of the discussions, conclusions and recommendations from that meeting.Meeting sessions included: a review of the efficacy of artemisinin-based combination therapy in Guyana and Suriname; the outcomes from a consultation on non-malaria febrile illness; the outcomes from the second meeting of the Evidence Review Group on malaria burden estimation; an update on the review of the WHO Guidelines for the Treatment of Malaria; an update regarding progress on the constitution of the vector control Technical Expert Group; updates on the RTS, S/AS01 vaccine and the malaria vaccine technology roadmap; financing and resource allocation for malaria control; malaria surveillance and the need for a surveillance, monitoring and evaluation Technical Expert Group; criteria and classification related to malaria elimination; the next meeting of the Evidence Review Group on Intermittent Preventive Treatment in pregnancy; an update on the soon-to-be launched Elimination Scenario Planning Tool; and an update on the process for the Global Technical Strategy for Malaria Control and Elimination (2016-2025).Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787092", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 329, "text": "the RTS,S/AS01 vaccine candidate represents the most developed and clinically validated malaria vaccine formulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21604980", "endSection": "abstract" } ] }, { "body": "What are the Topological Domains (TADs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25274727", "http://www.ncbi.nlm.nih.gov/pubmed/22495300", "http://www.ncbi.nlm.nih.gov/pubmed/25409831" ], "ideal_answer": [ "Topolological domains or TADs are megabase-sized local chromatin interaction domains which are a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. The boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002843" ], "type": "summary", "id": "569e6c68ca240fa209000001", "snippets": [ { "offsetInBeginSection": 940, "offsetInEndSection": 1690, "text": "We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495300", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The human genome is segmented into topologically associating domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274727", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 957, "text": "Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "abstract" } ] }, { "body": "What is the vibrational theory of olfaction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8985605", "http://www.ncbi.nlm.nih.gov/pubmed/25901328" ], "ideal_answer": [ "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. The theory proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations. It differs from previous vibrational theories (Dyson, Wright) in providing a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling. Thus, the authors, that have proposed this theory, suggest that olfaction, like colour vision and hearing, is a spectral sense." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012903", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055696", "http://amigo.geneontology.org/amigo/term/GO:0007608", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014732" ], "type": "summary", "id": "56c322d750c68dd416000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 477, "text": "It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations. It differs from previous vibrational theories (Dyson, Wright) in providing a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling. Elements of the tunnelling spectroscope are identified in putative olfactory receptors and their associated G-protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985605", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1130, "text": "The evidence presented here suggests instead that olfaction, like colour vision and hearing, is a spectral sense.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 446, "text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328", "endSection": "abstract" } ] }, { "body": "Are CTCF and BORIS involved in genome regulation and cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16140943", "http://www.ncbi.nlm.nih.gov/pubmed/17962299", "http://www.ncbi.nlm.nih.gov/pubmed/16140944", "http://www.ncbi.nlm.nih.gov/pubmed/21811597", "http://www.ncbi.nlm.nih.gov/pubmed/21465478", "http://www.ncbi.nlm.nih.gov/pubmed/24657531", "http://www.ncbi.nlm.nih.gov/pubmed/23390377", "http://www.ncbi.nlm.nih.gov/pubmed/12191639" ], "ideal_answer": [ "Yes. CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. CTCF has a single paralogue, the testes-specific CTCF-like gene (CTCFL)/BORIS. CTCF and BORIS can be deregulated in cancer. The tumour suppressor gene CTCF can be mutated or deleted in cancer, or CTCF DNA binding can be altered by epigenetic changes. BORIS is aberrantly expressed frequently in cancer, leading some to propose a pro-tumourigenic role for BORIS. However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation." ], "exact_answer": "yes", "type": "yesno", "id": "56a375f8496b62f23f000002", "snippets": [ { "offsetInBeginSection": 61, "offsetInEndSection": 829, "text": "CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. CTCF has a single paralogue, the testes-specific CTCF-like gene (CTCFL)/BORIS. CTCF and BORIS can be deregulated in cancer. The tumour suppressor gene CTCF can be mutated or deleted in cancer, or CTCF DNA binding can be altered by epigenetic changes. BORIS is aberrantly expressed frequently in cancer, leading some to propose a pro-tumourigenic role for BORIS. However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24657531", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 1104, "text": " The investigation of the molecular mechanisms engaged by CTCF to modulate tumor-related genes emphasizes the cell-type dependency of its tumor suppressor role. Indeed, the ability of CTCF to bind their promoters strictly depends by cell-type features as DNA methylation, BORIS-binding and post-translational modifications as PARYlation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21465478", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1368, "text": "Moreover, reduction of CTCF in normally BORIS-negative human fibroblasts resulted in derepression of BORIS promoters. These results provide a mechanistic basis for understanding cancer-related associations between haploinsufficiency of CTCF and BORIS derepression, and between the lack of functional p53 and aberrant activation of BORIS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "CTCF and BORIS in genome regulation and cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24657531", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12191639", "endSection": "title" }, { "offsetInBeginSection": 2164, "offsetInEndSection": 2444, "text": "Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140944", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 564, "text": "BORIS is the only known paralog of CTCF, a gene intimately involved in genomic imprinting, chromatin insulation, and nuclear regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390377", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1039, "text": "However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24657531", "endSection": "abstract" }, { "offsetInBeginSection": 2361, "offsetInEndSection": 2523, "text": "We suggest that BORIS is likely tethering epigenetic machinery to a novel class of CTCF/BORIS 11ZF target sequences that mediate induction of cancer-testis genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140943", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 623, "text": "Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a \"cancer-testis\" antigen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21811597", "endSection": "abstract" } ] }, { "body": "What is the application of the ASSET algorithm in C.elegans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21089077" ], "ideal_answer": [ "ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) is a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos. It gathers quantitative information with subcellular precision in the early Caenorhabditis elegans embryo, which is an attractive model to investigate evolutionarily conserved cellular mechanisms. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos.", "The early Caenorhabditis elegans embryo is an attractive model to investigate evolutionarily conserved cellular mechanisms. In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000465", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017173" ], "type": "summary", "id": "56c06ef5ef6e39474100001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "ASSET: a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1085, "text": "The early Caenorhabditis elegans embryo is an attractive model to investigate evolutionarily conserved cellular mechanisms. However, there is a paucity of automated methods to gather quantitative information with subcellular precision in this system. We developed ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) to fill this need. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos. We illustrate how ASSET can efficiently gather quantitative data on the motion of centrosomes and precisely track cortical invaginations, revealing hitherto unnoticed differences between wild-type and saps-1(RNAi) embryos. In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077", "endSection": "abstract" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1219, "text": "In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 722, "text": "We developed ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) to fill this need. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1085, "text": "In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077", "endSection": "abstract" } ] }, { "body": "Are Sidekick proteins members of the immunoglobulin superfamily?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15703275", "http://www.ncbi.nlm.nih.gov/pubmed/18216854" ], "ideal_answer": [ "Yes, sidekick are cell adhesion molecules of the immunoglobulin superfamily." ], "exact_answer": "yes", "type": "yesno", "id": "5709e947cf1c32585100001d", "snippets": [ { "offsetInBeginSection": 523, "offsetInEndSection": 708, "text": "Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18216854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Sidekick-1, a cell adhesion molecule of the immunoglobulin superfamily, is up-regulated in glomerular podocytes in the collapsing glomerulopathy of HIV-associated nephropathy (HIVAN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703275", "endSection": "abstract" } ] }, { "body": "What are the pyknons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16751093", "http://www.ncbi.nlm.nih.gov/pubmed/19229130", "http://www.ncbi.nlm.nih.gov/pubmed/16636294", "http://www.ncbi.nlm.nih.gov/pubmed/19452047" ], "ideal_answer": [ "Using an unsupervised pattern-discovery method, the human intergenic and intronic regions were processed and all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance were catalogued. Among the millions of discovered patterns, a subset of 127,998 patterns was found, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics. Pyknons might represent a biologically important link between coding and non-coding DNA." ], "type": "summary", "id": "553a9aa3f321868558000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 471, "text": "Using an unsupervised pattern-discovery method, we processed the human intergenic and intronic regions and catalogued all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance. Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16636294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "In a recent paper in PNAS, Rigoutsos et al. (2006) describe a nonrandom pattern of repeated elements, called pyknons, which are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Discovery of pyknons, the most frequent, variable-length DNA sequence motifs in the human genomes, suggests extensive sequence-based connectivity between non-coding and protein-coding components of human genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19229130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16636294", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 417, "text": "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes. They are interesting because they portend an unforeseen connection between coding and non-coding DNA. Pyknons have only been discovered in the human genome, so it is unknown whether pyknons have wider biological relevance or are simply a phenomenon of the human genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1335, "text": "these data reveal that pyknons represent a biologically important link between coding and non-coding DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19452047", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 595, "text": "The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16636294", "endSection": "abstract" } ] }, { "body": "Which deiodinases are best known to be present in brain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22294745", "http://www.ncbi.nlm.nih.gov/pubmed/16728541", "http://www.ncbi.nlm.nih.gov/pubmed/8663170", "http://www.ncbi.nlm.nih.gov/pubmed/7768329", "http://www.ncbi.nlm.nih.gov/pubmed/10426574", "http://www.ncbi.nlm.nih.gov/pubmed/22719854", "http://www.ncbi.nlm.nih.gov/pubmed/1417847", "http://www.ncbi.nlm.nih.gov/pubmed/8444882", "http://www.ncbi.nlm.nih.gov/pubmed/15062548", "http://www.ncbi.nlm.nih.gov/pubmed/12072404" ], "ideal_answer": [ "All the 3 deiodinases (Type 1, Type 2 and Type 3 deiodinase) are present in the \"brain\" but Type 1 deiodinase is only found in neurohypophysis that cannot be actually considered true \"brain tissue\"." ], "exact_answer": [ [ "Type 2 deiodinase" ], [ "Type 3 deiodinase" ] ], "type": "list", "id": "517a8bab8ed59a060a000040", "snippets": [ { "offsetInBeginSection": 181, "offsetInEndSection": 307, "text": "In brain, the presence of type III iodothyronine deiodinase (D3) seems to be important to maintain homeostasis of T(3) levels.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12072404", "endSection": "sections.0" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1750, "text": "We were able to detect a protein fragment corresponding to the expected molecular mass (30 kDa) for type III deiodinase by means of Western blot analysis. RT-PCR as well as Northern blot analysis confirmed the presence of D3 mRNA in the cerebellum.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12072404", "endSection": "sections.0" }, { "offsetInBeginSection": 345, "offsetInEndSection": 583, "text": "The presence of 5D (type-III) together with our previous report of 5'-deiodinase (type-I in euthyroidism and type-II in hypothyroidism) shows that the isozymes of deiodinases in the neurohypophysis are quite similar to those in the brain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1417847", "endSection": "sections.0" } ] }, { "body": "What are the computational methods for the prediction of beta-barrel transmembrane proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15647112", "http://www.ncbi.nlm.nih.gov/pubmed/16844989", "http://www.ncbi.nlm.nih.gov/pubmed/23530628", "http://www.ncbi.nlm.nih.gov/pubmed/15980447", "http://www.ncbi.nlm.nih.gov/pubmed/15162482", "http://www.ncbi.nlm.nih.gov/pubmed/19153681", "http://www.ncbi.nlm.nih.gov/pubmed/22148174", "http://www.ncbi.nlm.nih.gov/pubmed/12798041", "http://www.ncbi.nlm.nih.gov/pubmed/19429691", "http://www.ncbi.nlm.nih.gov/pubmed/21328706", "http://www.ncbi.nlm.nih.gov/pubmed/17520325", "http://www.ncbi.nlm.nih.gov/pubmed/23297037", "http://www.ncbi.nlm.nih.gov/pubmed/22540951", "http://www.ncbi.nlm.nih.gov/pubmed/18989393", "http://www.ncbi.nlm.nih.gov/pubmed/19622743", "http://www.ncbi.nlm.nih.gov/pubmed/18006547", "http://www.ncbi.nlm.nih.gov/pubmed/12192075", "http://www.ncbi.nlm.nih.gov/pubmed/21935968", "http://www.ncbi.nlm.nih.gov/pubmed/21426944", "http://www.ncbi.nlm.nih.gov/pubmed/12169530", "http://www.ncbi.nlm.nih.gov/pubmed/19470175", "http://www.ncbi.nlm.nih.gov/pubmed/12070338", "http://www.ncbi.nlm.nih.gov/pubmed/18218108", "http://www.ncbi.nlm.nih.gov/pubmed/21967762", "http://www.ncbi.nlm.nih.gov/pubmed/15141026", "http://www.ncbi.nlm.nih.gov/pubmed/18467177", "http://www.ncbi.nlm.nih.gov/pubmed/19421989", "http://www.ncbi.nlm.nih.gov/pubmed/15215418", "http://www.ncbi.nlm.nih.gov/pubmed/22987359", "http://www.ncbi.nlm.nih.gov/pubmed/15070403", "http://www.ncbi.nlm.nih.gov/pubmed/15769290", "http://www.ncbi.nlm.nih.gov/pubmed/17597890", "http://www.ncbi.nlm.nih.gov/pubmed/21064129", "http://www.ncbi.nlm.nih.gov/pubmed/17597895", "http://www.ncbi.nlm.nih.gov/pubmed/15215419", "http://www.ncbi.nlm.nih.gov/pubmed/22031179", "http://www.ncbi.nlm.nih.gov/pubmed/16858668", "http://www.ncbi.nlm.nih.gov/pubmed/21531175", "http://www.ncbi.nlm.nih.gov/pubmed/17088282", "http://www.ncbi.nlm.nih.gov/pubmed/16225682", "http://www.ncbi.nlm.nih.gov/pubmed/16674095", "http://www.ncbi.nlm.nih.gov/pubmed/18312695", "http://www.ncbi.nlm.nih.gov/pubmed/10698111", "http://www.ncbi.nlm.nih.gov/pubmed/16597327", "http://www.ncbi.nlm.nih.gov/pubmed/22247276", "http://www.ncbi.nlm.nih.gov/pubmed/20488436", "http://www.ncbi.nlm.nih.gov/pubmed/11274469", "http://www.ncbi.nlm.nih.gov/pubmed/17958348", "http://www.ncbi.nlm.nih.gov/pubmed/18355838" ], "ideal_answer": [ "Computational tools have been developed for beta-barrel transmembrane protein discrimination, topology prediction and prediction of their structural features.\nInitial methods developed for the prediction of the transmembrane beta strands were based on hydrophobicity analysis, using sliding windows along the sequence, in order to capture the alternating patterns of hydrophobic-hydrophilic residues of the transmembrane strands, or using generalized secondary structure prediction methods. Other approaches included the construction of special empirical rules using amino-acid propensities and prior knowledge of the structural nature of the proteins, and the development of Neural Network-based predictors to predict the location of alpha-carbon atoms with respect to the membrane. During the last few years, other more refined methods, appeared, including: Neural Networks, Hidden Markov Models, Support Vector Machines, k-Nearest Neighbors, Radial Basis Functions, Bayesian Networks, Genetic Algorithms, Mahalanobis Discriminant Functions, Cellular Automata, N-to-1 Extreme Learning Machines. Hidden Markov Model-based methods are among the most successful in topology prediction, being able to capture the unique architecture of beta-barrel transmembrane proteins. Consensus methods, as well as pipelines of several related tools (e.g. subcellular localization prediciton, alpha-helical transmembrane protein prediction, signal-peptide/lipoprotein prediction) have also used for discriminating beta-barrel transmembrane proteins. Recently, a number of methods for predicting more detailed structural features (e.g. surface accessibility, residue contacts, even detailed atomic 3D models) tailored to beta-barrel transmembrane proteins have been developed, based on knowledge-based potential functions, graph theoretic models, physical models and multi-tape S-attribute grammars. Methods/tools falling in the aforementioned classes are (listed in alphabetical order): BBF (beta-barrel finder), BETAWARE, BOCTOPUS, BOMP, BTMX (Beta barrel TransMembrane eXposure), HHomp, HMM-B2TMR, OMBBpred, PROFtmb, PRED-TMBB, TMB-Hunt, TBBPred, TMBETAPRED-RBF, TMBHMM, TransFold, TMBpro, TMBKNN, Wimley" ], "exact_answer": [ [ "BBF", "beta-barrel finder" ], [ "BETAWARE" ], [ "BOCTOPUS" ], [ "BOMP" ], [ "BTMX", "Beta barrel TransMembrane eXposure" ], [ "HHomp" ], [ "HMM-B2TMR" ], [ "OMBBpred" ], [ "PROFtmb" ], [ "PRED-TMBB" ], [ "TMB-Hunt" ], [ "TBBPred" ], [ "TMBETAPRED-RBF" ], [ "TMBHMM" ], [ "TransFold" ], [ "TMBpro" ], [ "TMBKNN" ], [ "Wimley" ], [ "TMBETA-NET" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016021", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984" ], "type": "list", "id": "5149a61ed24251bc05000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "BETAWARE: a machine-learning tool to detect and predict transmembrane beta-barrel proteins in prokaryotes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037", "endSection": "title" }, { "offsetInBeginSection": 684, "offsetInEndSection": 1063, "text": "Recently, we developed two top-performing methods based on machine-learning approaches to tackle both the detection of TMBBs in sets of proteins and the prediction of their topology. Here, we present our BETAWARE program that includes both approaches and can run as a standalone program on a linux-based computer to easily address in-home massive protein annotation or filtering.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 618, "text": "We introduce a graph-theoretic model for predicting the supersecondary structure of transmembrane \u03b2-barrel proteins--a particular class of proteins that performs diverse important functions but it is difficult to determine their structure with experimental methods. This ab initio model resolves the protein folding problem based on pseudo-energy minimization with the aid of a simple probabilistic filter. It also allows for determining structures whose barrel follows a given permutation on the arrangement of \u03b2-strands, and allows for rapidly discriminating the transmembrane \u03b2-barrels from other kinds of proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987359", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "BOCTOPUS: improved topology prediction of transmembrane \u03b2 barrel proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247276", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Improving the detection of transmembrane \u03b2-barrel chains with N-to-1 extreme learning machines", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21967762", "endSection": "title" }, { "offsetInBeginSection": 728, "offsetInEndSection": 833, "text": "we introduce a new machine learning approach for TMBB detection based on N-to-1 Extreme Learning Machines", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21967762", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "TMBHMM: a frequency profile based HMM for predicting the topology of transmembrane beta barrel proteins and the exposure status of transmembrane residues", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 838, "text": "We present here TMBHMM, a computational method based on a hidden Markov model for predicting the structural topology of putative TMBs from sequence. In addition to predicting transmembrane strands, TMBHMM also predicts the exposure status (i.e., exposed to the membrane or hidden in the protein structure) of the residues in the transmembrane region, which is a novel feature of the TMBHMM method. Furthermore, TMBHMM can also predict the membrane residues that are not part of beta barrel forming strands.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Prediction of the exposure status of transmembrane beta barrel residues from protein sequence", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21328706", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "We present BTMX (Beta barrel TransMembrane eXposure), a computational method to predict the exposure status (i.e. exposed to the bilayer or hidden in the protein structure) of transmembrane residues in transmembrane beta barrel proteins (TMBs).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21328706", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Combined prediction of transmembrane topology and signal peptide of beta-barrel proteins: using a hidden Markov model and genetic algorithms", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20488436", "endSection": "title" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1043, "text": "We present here, an HMM that combine a transmembrane barrel submodel and an SP submodel for both topology and SP predictions. A new genetic algorithm (GA) is presented here to training the model, at the same time the Posterior-Viterbi algorithm is adopted for decoding.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20488436", "endSection": "sections.0" }, { "offsetInBeginSection": 168, "offsetInEndSection": 332, "text": "In this work, we propose a method based on radial basis networks for predicting the number of beta-strands in OMPs and identifying their membrane spanning segments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989", "endSection": "sections.0" }, { "offsetInBeginSection": 624, "offsetInEndSection": 805, "text": "We have developed a web server, TMBETAPRED-RBF for predicting the transmembrane beta-strands from amino acid sequence and it is available at http://rbf.bioinfo.tw/~sachen/tmrbf.html", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 607, "text": "We have developed a novel approach for dissecting transmembrane beta-barrel proteins (TMBs) in genomic sequences. The features include (i) the identification of TMBs using the preference of residue pairs in globular, transmembrane helical (TMH) and TMBs, (ii) elimination of globular/TMH proteins that show sequence identity of more than 70% for the coverage of 80% residues with known structures, (iii) elimination of globular/TMH proteins that have sequence identity of more than 60% with known sequences in SWISS-PROT, and (iv) exclusion of TMH proteins using SOSUI, a prediction system for TMH proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17958348", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "TMBpro: secondary structure, beta-contact and tertiary structure prediction of transmembrane beta-barrel proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006547", "endSection": "title" }, { "offsetInBeginSection": 732, "offsetInEndSection": 934, "text": "We develop a suite (TMBpro) of specialized predictors for predicting secondary structure (TMBpro-SS), beta-contacts (TMBpro-CON) and tertiary structure (TMBpro-3D) of transmembrane beta-barrel proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006547", "endSection": "sections.0" }, { "offsetInBeginSection": 100, "offsetInEndSection": 199, "text": "This paper presents a k-nearest neighbor (K-NN) method for discriminating TMB and non-TMB proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467177", "endSection": "sections.0" }, { "offsetInBeginSection": 533, "offsetInEndSection": 1022, "text": "In this paper, based on the concept of pseudo amino acid composition (PseAA) that can incorporate sequence-order information of a protein sequence so as to remarkably enhance the power of discrete models (Chou, K. C., Proteins: Structure, Function, and Genetics, 2001, 43: 246-255), cellular automata and Lempel-Ziv complexity are introduced to predict the TM regions of integral membrane proteins including both alpha-helical and beta-barrel membrane proteins, validated by jackknife test", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17520325", "endSection": "sections.0" }, { "offsetInBeginSection": 486, "offsetInEndSection": 737, "text": "we present BOCTOPUS; an improved method for the topology prediction of TMBs by employing a combination of support vector machines (SVMs) and Hidden Markov Models (HMMs). The SVMs and HMMs account for local and global residue preferences, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247276", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "PRED-TMBB: a web server for predicting the topology of beta-barrel outer membrane proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215419", "endSection": "title" }, { "offsetInBeginSection": 346, "offsetInEndSection": 684, "text": "We present here a web server (PRED-TMBB, http://bioinformatics.biol.uoa.gr/PRED-TMBB) which is capable of predicting the transmembrane strands and the topology of beta-barrel outer membrane proteins of Gram-negative bacteria. The method is based on a Hidden Markov Model, trained according to the Conditional Maximum Likelihood criterion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215419", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Prediction of transmembrane regions of beta-barrel proteins using ANN- and SVM-based methods", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 325, "text": "his article describes a method developed for predicting transmembrane beta-barrel regions in membrane proteins using machine learning techniques: artificial neural network (ANN) and support vector machine (SVM). The ANN used in this study is a feed-forward neural network with a standard back-propagation training algorithm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482", "endSection": "sections.0" }, { "offsetInBeginSection": 527, "offsetInEndSection": 845, "text": "We have also developed an SVM-based method using a primary sequence as input and achieved an accuracy of 77.4%. The SVM model was modified by adding 36 physicochemical parameters to the amino acid sequence information. Finally, ANN- and SVM-based methods were combined to utilize the full potential of both techniques.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482", "endSection": "sections.0" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1291, "text": "we have developed a Web server, TBBPred, for predicting transmembrane beta-barrel regions in proteins", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Predicting transmembrane beta-barrels in proteomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026", "endSection": "title" }, { "offsetInBeginSection": 241, "offsetInEndSection": 386, "text": "Here we introduced the design, statistics and results of a novel profile-based hidden Markov model for the prediction and discrimination of TMBs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026", "endSection": "sections.0" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1453, "text": "All proteome predictions and the PROFtmb prediction method are available", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The beta-barrel finder (BBF) program, allowing identification of outer membrane beta-barrel proteins encoded within prokaryotic genomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12192075", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 795, "text": "We here report computational analyses of six outer membrane proteins of known 3D structures with respect to (1) secondary structure, (2) hydropathy, and (3) amphipathicity. Using these characteristics, as well as the presence of an N-terminal targeting sequence, a program was developed allowing prediction of integral membrane beta-barrel proteins encoded within any completely sequenced prokaryotic genome. This program, termed the beta-barrel finder (BBF) program, was used to analyze the proteins encoded within the Escherichia coli genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12192075", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "A sequence-profile-based HMM for predicting and discriminating beta barrel membrane proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12169530", "endSection": "title" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1485, "text": "We develop a HMM model, which can predict the topology of beta barrel membrane proteins using, as input, evolutionary information. The model is cyclic with 6 types of states: two for the beta strand transmembrane core, one for the beta strand cap on either side of the membrane, one for the inner loop, one for the outer loop and one for the globular domain state in the middle of each loop. The development of a specific input for HMM based on multiple sequence alignment is novel.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12169530", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Prediction of the transmembrane regions of beta-barrel membrane proteins with a neural network-based predictor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11274469", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "A method based on neural networks is trained and tested on a nonredundant set of beta-barrel membrane proteins known at atomic resolution with a jackknife procedure. The method predicts the topography of transmembrane beta strands with residue accuracy as high as 78% when evolutionary information is used as input to the network.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11274469", "endSection": "sections.0" }, { "offsetInBeginSection": 570, "offsetInEndSection": 682, "text": "A web server based on the proposed method is available at http://yanbioinformatics.cs.usu.edu:8080/TMBKNNsubmit.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467177", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Predicting three-dimensional structures of transmembrane domains of \u03b2-barrel membrane proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22148174", "endSection": "title" }, { "offsetInBeginSection": 391, "offsetInEndSection": 887, "text": "We have developed a computational method for predicting structures of the transmembrane (TM) domains of \u03b2-barrel membrane proteins. Based on physical principles, our method can predict structures of the TM domain of \u03b2-barrel membrane proteins of novel topology, including those from eukaryotic mitochondria. Our method is based on a model of physical interactions, a discrete conformational state space, an empirical potential function, as well as a model to account for interstrand loop entropy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22148174", "endSection": "sections.0" }, { "offsetInBeginSection": 25, "offsetInEndSection": 93, "text": "exposure status classification of transmembrane beta barrel residues", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21531175", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 436, "text": "Several computational methods exist for the identification of transmembrane beta barrel proteins (TMBs) from sequence. Some of these methods also provide the transmembrane (TM) boundaries of the putative TMBs. The aim of this study is to (1) derive the propensities of the TM residues to be exposed to the lipid bilayer and (2) to predict the exposure status (i.e. exposed to the bilayer or hidden in protein structure) of TMB residues.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21531175", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The modified Mahalanobis Discriminant for predicting outer membrane proteins by using Chou's pseudo amino acid composition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18355838", "endSection": "title" }, { "offsetInBeginSection": 224, "offsetInEndSection": 508, "text": "In this study, a method that combines increment of diversity with modified Mahalanobis Discriminant, called IDQD, is presented to predict 208 OMPs, 206 transmembrane helical proteins (TMHPs) and 673 globular proteins (GPs) by using Chou's pseudo amino acid compositions as parameters.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18355838", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Predicting transmembrane beta-barrels and interstrand residue interactions from sequence", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16858668", "endSection": "title" }, { "offsetInBeginSection": 460, "offsetInEndSection": 928, "text": "A novel method using pairwise interstrand residue statistical potentials derived from globular (nonouter membrane) proteins is introduced to predict the supersecondary structure of transmembrane beta-barrel proteins. The algorithm transFold employs a generalized hidden Markov model (i.e., multitape S-attribute grammar) to describe potential beta-barrel supersecondary structures and then computes by dynamic programming the minimum free energy beta-barrel structure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16858668", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Predicting the solvent accessibility of transmembrane residues from protein sequence", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16674095", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "In this study, we propose a novel method to predict the solvent accessible surface areas of transmembrane residues. For both transmembrane alpha-helix and beta-barrel residues, the correlation coefficients between the predicted and observed accessible surface areas are around 0.65.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16674095", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "BOMP: a program to predict integral beta-barrel outer membrane proteins encoded within genomes of Gram-negative bacteria", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215418", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 623, "text": "This work describes the development of a program that predicts whether or not a polypeptide sequence from a Gram-negative bacterium is an integral beta-barrel outer membrane protein. The program, called the beta-barrel Outer Membrane protein Predictor (BOMP), is based on two separate components to recognize integral beta-barrel proteins. The first component is a C-terminal pattern typical of many integral beta-barrel proteins. The second component calculates an integral beta-barrel score of the sequence based on the extent to which the sequence contains stretches of amino acids typical of transmembrane beta-strands.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215418", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "A HMM-based method to predict the transmembrane regions of beta-barrel membrane proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12798041", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "A novel method is developed to model and predict the transmembrane regions of beta-barrel membrane proteins. It is based on a Hidden Markov model (HMM) with architecture obeying those proteins' construction principles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12798041", "endSection": "sections.0" }, { "offsetInBeginSection": 271, "offsetInEndSection": 649, "text": "First, an algorithm that calculates the mean hydrophobicity of one side of putative beta-strands predicted the positions of 16 transmembrane segments, a structure common to known porins. Second, outer loops typical of porins were assigned using an artificial neural network trained to predict the topology of bacterial outer-membrane proteins with a predominance of beta-strands", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12070338", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Prediction of the membrane-spanning beta-strands of the major outer membrane protein of Chlamydia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12070338", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Topology prediction of Brucella abortus Omp2b and Omp2a porins after critical assessment of transmembrane beta strands prediction by several secondary structure prediction methods", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10698111", "endSection": "title" }, { "offsetInBeginSection": 162, "offsetInEndSection": 671, "text": "Four porins of known structure were selected as test-cases and their secondary structure delineated. The specificity and sensitivity of 11 methods were separately evaluated. Our critical assessment shows that some secondary structure prediction methods (PHD, Dsc, Sopma) originally designed to predict globular protein structure are useful on porin topology prediction. The overall best prediction is obtained by combining these three \"generalist\" methods with a transmembrane beta strand prediction technique", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10698111", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "A knowledge-based potential highlights unique features of membrane \u03b1-helical and \u03b2-barrel protein insertion and folding", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22031179", "endSection": "title" }, { "offsetInBeginSection": 323, "offsetInEndSection": 796, "text": "In previous work, a depth-dependent insertion potential, E(z) , was derived for \u03b1-helical inner membrane proteins. We have generated an equivalent potential for TM \u03b2-barrel proteins. The similarities and differences between these two potentials provide insight into unique aspects of the folding and insertion of \u03b2-barrel membrane proteins. This potential can predict orientation within the membrane and identify functional residues involved in intermolecular interactions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22031179", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Improved identification of outer membrane beta barrel proteins using primary sequence, predicted secondary structure, and evolutionary information", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21064129", "endSection": "title" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1035, "text": "We present an accurate sequence-based predictor of OMBBs, called OMBBpred, which utilizes a Support Vector Machine classifier and a custom-designed set of 34 novel numerical descriptors derived from predicted secondary structures, hydrophobicity, and evolutionary information.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21064129", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Predicting weakly stable regions, oligomerization state, and protein-protein interfaces in transmembrane domains of outer membrane proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622743", "endSection": "title" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1461, "text": "We have also discovered that out-clamps, in-plugs, and oligomerization are 3 general mechanisms for stabilizing weakly stable TM regions. In addition, we have found that extended and contiguous weakly stable regions often signal the existence of an oligomer and that strands located in the interfaces of protein-protein interactions are considerably less stable. Based on these observations, we can predict oligomerization states and can identify the interfaces of protein-protein interactions for beta-barrel membrane proteins by using either structure or sequence information", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622743", "endSection": "sections.0" }, { "offsetInBeginSection": 688, "offsetInEndSection": 870, "text": "Recently, we developed two top-performing methods based on machine-learning approaches to tackle both the detection of TMBBs in sets of proteins and the prediction of their topology.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "We introduce a graph-theoretic model for predicting the supersecondary structure of transmembrane \u03b2-barrel proteins--a particular class of proteins that performs diverse important functions but it is difficult to determine their structure with experimental methods.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987359", "endSection": "sections.0" }, { "offsetInBeginSection": 508, "offsetInEndSection": 609, "text": "Several computational methods have been developed to discriminate TMBBs from other types of proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21967762", "endSection": "sections.0" }, { "offsetInBeginSection": 563, "offsetInEndSection": 711, "text": "To conquer this limitation, we developed a new computational model that can be used for predicting the ASA of both TM \u03b1-helix and \u03b2-barrel residues.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21935968", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Transmembrane beta barrel (TMB) proteins are found in the outer membranes of bacteria, mitochondria and chloroplasts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944", "endSection": "sections.0" }, { "offsetInBeginSection": 765, "offsetInEndSection": 899, "text": "RESULTS: We present here, an HMM that combine a transmembrane barrel submodel and an SP submodel for both topology and SP predictions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20488436", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Prediction of membrane spanning segments in beta-barrel outer membrane proteins (OMP) and their topology is an important problem in structural and functional genomics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989", "endSection": "sections.0" }, { "offsetInBeginSection": 331, "offsetInEndSection": 531, "text": "In the simplest of these, the target \"model\" is another protein sequence, while the more elaborate methods group together the entire set of t ansmembrane helical or transmembrane beta-barrel proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19153681", "endSection": "sections.0" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1348, "text": "Based on this study, we have developed a Web server, TBBPred, for predicting transmembrane beta-barrel regions in proteins (available at http://www.imtech.res.in/raghava/tbbpred).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15162482", "endSection": "sections.0" } ] }, { "body": "Describe what is the usage of the Theatre software tool for genomic analysis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12824356" ], "ideal_answer": [ "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. In addition to web-based output, Theatre can produce publication quality colour hardcopies showing predicted features in aligned genomic sequences.", "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. Theatre can be accessed at http://www.hgmp.mrc.ac.uk/Registered/Webapp/theatre/." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281" ], "type": "summary", "id": "56b8a525156496395c000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 726, "text": "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. In addition to web-based output, Theatre can produce publication quality colour hardcopies showing predicted features in aligned genomic sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Theatre: A software tool for detailed comparative analysis and visualization of genomic sequence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824356", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 440, "text": "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824356", "endSection": "abstract" } ] }, { "body": "How are CRM (cis-regulatory modules) defined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25268582", "http://www.ncbi.nlm.nih.gov/pubmed/17711474", "http://www.ncbi.nlm.nih.gov/pubmed/14534164", "http://www.ncbi.nlm.nih.gov/pubmed/15757364", "http://www.ncbi.nlm.nih.gov/pubmed/15883375", "http://www.ncbi.nlm.nih.gov/pubmed/25442502", "http://www.ncbi.nlm.nih.gov/pubmed/19660565", "http://www.ncbi.nlm.nih.gov/pubmed/19820186", "http://www.ncbi.nlm.nih.gov/pubmed/15215390", "http://www.ncbi.nlm.nih.gov/pubmed/22877946", "http://www.ncbi.nlm.nih.gov/pubmed/23409927", "http://www.ncbi.nlm.nih.gov/pubmed/15677727", "http://www.ncbi.nlm.nih.gov/pubmed/16980320", "http://www.ncbi.nlm.nih.gov/pubmed/22492356", "http://www.ncbi.nlm.nih.gov/pubmed/21152003" ], "ideal_answer": [ "Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules.", "In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs).", "Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). ", "CisMiner can be queried for the results presented in this work and can also perform a customized cis-regulatory module prediction on a query set of transcription factor binding sites provided by the user. In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules. Our web server is available at http://creme.dcode.org." ], "type": "summary", "id": "56f3eebd2ac5ed1459000016", "snippets": [ { "offsetInBeginSection": 137, "offsetInEndSection": 281, "text": "Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215390", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 303, "text": "In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15883375", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 604, "text": "This conserved sequence has therefore been proposed to act as a long-range, cis-acting regulator of limb-specific Shh expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15677727", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1187, "text": "The conserved upstream sequence can activate gene expression from basal promoters in the brain vesicle, although it requires additional cis-regulatory sequences to fully activate the CNS-specific gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17711474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The genomic instructions used to regulate development are encoded within a set of functional DNA elements called cis-regulatory modules ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19660565", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 404, "text": "Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268582", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 714, "text": "However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19820186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "The identification of transcription factor binding sites (TFBSs) and cis-regulatory modules (CRMs) is a crucial step in studying gene expression, but the computational method attempting to distinguish CRMs from NCNRs still remains a challenging problem due to the limited knowledge of specific interactions involved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23409927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "In eukaryotes, transcriptional regulation is usually mediated by interactions of multiple transcription factors (TFs) with their respective specific cis-regulatory elements (CREs) in the so-called cis-regulatory modules (CRMs) in DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The transcriptional regulation of a metazoan gene depends on the cooperative action of multiple transcription factors that bind to cis-regulatory modules (CRMs) located in the neighborhood of the gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14534164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492356", "endSection": "title" }, { "offsetInBeginSection": 631, "offsetInEndSection": 756, "text": "We also identified potential cis-regulatory modules (CRMs) defined as clusters of conserved TFBSs in the entire mouse genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16980320", "endSection": "abstract" } ] }, { "body": "Which is the main regulatory molecule of SERCA2A function in the cardiac muscle?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23710633", "http://www.ncbi.nlm.nih.gov/pubmed/25451386", "http://www.ncbi.nlm.nih.gov/pubmed/19112098", "http://www.ncbi.nlm.nih.gov/pubmed/18971376", "http://www.ncbi.nlm.nih.gov/pubmed/10555147", "http://www.ncbi.nlm.nih.gov/pubmed/19948724", "http://www.ncbi.nlm.nih.gov/pubmed/21266500", "http://www.ncbi.nlm.nih.gov/pubmed/18415121", "http://www.ncbi.nlm.nih.gov/pubmed/18508637", "http://www.ncbi.nlm.nih.gov/pubmed/11371203", "http://www.ncbi.nlm.nih.gov/pubmed/15598648" ], "ideal_answer": [ "SERCA2a activity is regulated by phosphorylation of another SR protein, Phospholamban (PLN). Phospholamban (PLB) inhibits the activity of SERCA2a, the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, by decreasing the apparent affinity of the enzyme for Ca(2+)." ], "exact_answer": [ "Phospholamban", "PLN", "plb" ], "type": "factoid", "id": "54cb9c94f693c3b16b000005", "snippets": [ { "offsetInBeginSection": 406, "offsetInEndSection": 705, "text": "SR Ca-transport is mediated by the SR Ca-ATPase (SERCA2a) and its regulatory phosphoprotein, phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA2a and phosphorylation by protein kinase A (PKA) or calcium-calmodulin-dependent protein kinases (CAMKII) relieves these inhibitory effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451386", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 976, "text": "SERCA2a activity can be regulated at multiple levels of a signaling cascade comprised of phospholamban", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23710633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Phospholamban (PLN), the reversible inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), is a key regulator of myocyte Ca(2+) cycling with a significant role in heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21266500", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 271, "text": "The sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971376", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 762, "text": "phospholamban (PLN), a muscle-specific SR Ca(2+)-ATPase (SERCA2a) inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15598648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, and functions as an endogenous inhibitor of Ca-ATPase transport activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11371203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Phospholamban (PLB) inhibits the activity of SERCA2a, the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, by decreasing the apparent affinity of the enzyme for Ca(2+).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19112098", "endSection": "abstract" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1304, "text": "phospholamban regulation of SERCA2a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19112098", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 530, "text": "SERCA2a activity is regulated by phosphorylation of another SR protein: Phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a. Phosphorylation of PLN by either cAMP or cGMP-dependent protein kinase at Ser16 or the Ca2+-calmodulin-dependent protein kinase (CaMKII), at Thr17, relieves this inhibition, increasing SR Ca2+ uptake and SR Ca2+ load.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18508637", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 532, "text": "The ablation of a muscle-specific sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) inhibitor, phospholamban, rescued the spectrum of phenotypes that resemble human heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10555147", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 495, "text": "The sarco(endo)plasmic reticulum Ca(2+) transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca(2+) homeostasis and, therefore, cardiac function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18415121", "endSection": "abstract" } ] }, { "body": "Which gene is responsible for the development of the Mowat-Wilson syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "http://www.ncbi.nlm.nih.gov/pubmed/17932455", "http://www.ncbi.nlm.nih.gov/pubmed/24092421", "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "http://www.ncbi.nlm.nih.gov/pubmed/16688751", "http://www.ncbi.nlm.nih.gov/pubmed/24029077", "http://www.ncbi.nlm.nih.gov/pubmed/17103451", "http://www.ncbi.nlm.nih.gov/pubmed/11891681", "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "http://www.ncbi.nlm.nih.gov/pubmed/20125191", "http://www.ncbi.nlm.nih.gov/pubmed/15006694", "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "http://www.ncbi.nlm.nih.gov/pubmed/17478475" ], "ideal_answer": [ "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene.", "Nonsense mutations of the ZFHX1B gene in two Japanese girls with Mowat-Wilson syndromezfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.", "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B, also known as ZEB2 or SIP-1).", "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies. Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development" ], "exact_answer": [ "ZFHX1B", "ZEB2", "SIP-1" ], "type": "factoid", "id": "5519113b622b19434500000f", "snippets": [ { "offsetInBeginSection": 219, "offsetInEndSection": 275, "text": "The cause of MWS is a de novo mutation in the ZEB2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 171, "text": "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "endSection": "title" }, { "offsetInBeginSection": 458, "offsetInEndSection": 565, "text": "We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Comprehensive ZEB2 gene analysis for Mowat-Wilson syndrome in a North American cohort: a suggested approach to molecular diagnostics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "A case of Mowat-Wilson syndrome caused by a truncating mutation within exon 8 of the ZEB2 gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "endSection": "title" }, { "offsetInBeginSection": 456, "offsetInEndSection": 602, "text": "All typical cases result from haploinsufficiency of the ZEB2 (also known as ZFHX1B or SIP-1) gene, with over 100 distinct mutations now described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 774, "text": "Approximately 80% of patients have a nonsense or frameshift mutation detectable by sequencing, with the rest having gross deletions necessitating a dosage sensitive assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1127, "text": "Six patients had deletions in the ZEB2 gene, including two novel partial gene deletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1373, "text": "This report, the first such analysis in North American patients, adds to the growing list of both novel pathogenic mutations associated with MWS, as well as other variants in the ZEB2 gene. In addition, we suggest an economical testing strategy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Nonsense mutations of the ZFHX1B gene in two Japanese girls with Mowat-Wilson syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 915, "text": "According to the gene analysis using white blood cells, they had nonsense mutations in ZFHX1B, R695X and Q433X, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1074, "text": "In conclusion, molecular genetic analysis of ZFHX1B is important for a definite diagnosis of MWS which has a wide phenotypic spectrum of congenital anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "A missense mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 638, "text": "Mutations leading to haploinsufficiency of the ZFHX1B gene have been described as the underlying cause of this condition. We report on the clinical findings in a 2(1/2)-year-old boy with some aspects out of the MWS-spectrum in addition to unusual anomalies and a novel missense mutation in the ZFHX1B gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Genitourinary anomalies in Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "endSection": "title" }, { "offsetInBeginSection": 422, "offsetInEndSection": 500, "text": "It is caused by mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Pleiotropic and diverse expression of ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the \"Mowat-Wilson\" syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "ZFHX1B encodes Smad-interacting protein 1, a transcriptional corepressor involved in the transforming growth factors beta (TGFbeta) signaling pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 287, "text": "ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "endSection": "title" }, { "offsetInBeginSection": 188, "offsetInEndSection": 440, "text": "Mutation analysis of the zinc finger homeo box 1 B (ZFHX1 B) gene revealed a de novo 7 bp deletion (TGGCCCC) at nucleotide 1773 (1773 delTGGCCCC) resulting in a frameshift and leading to a termination codon at amino acid residue 604 (604 X) in exon 8 C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "\"Mowat-Wilson\" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11891681", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 390, "text": "Recently mutations in the gene ZFHX1B (SIP1) were shown in patients with \"syndromic Hirschsprung disease\" with mental retardation (MR) and multiple congenital anomalies (MCA), but it was unclear if Hirschsprung disease is an obligate symptom of these mutations and if the distinct facial phenotype delineated by Mowat et al. [1998: J Med Genet 35: 617-623] is specific for ZFHX1B mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11891681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "endSection": "title" }, { "offsetInBeginSection": 117, "offsetInEndSection": 294, "text": "Haploinsufficiency of a gene termed ZFHX1B (also known as SIP1) on chromosome 2 is responsible for this condition, and clinical genetic testing for MWS recently became available", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Mowat-Wilson syndrome is a recently delineated autosomal dominant developmental anomaly, whereby heterozygous mutations in the ZFHX1B gene cause mental retardation, delayed motor development, epilepsy and a wide spectrum of clinically heterogeneous features, suggestive of neurocristopathies at the cephalic, cardiac and vagal levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17478475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21336163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "ZFHX1B mutations in patients with Mowat-Wilson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "endSection": "title" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1119, "text": "A similar issue of differential diagnosis was raised by a large 4.3 Mb 2q22.3q23.1 deletion encompassing ZEB2, the gene responsible for the Mowat-Wilson syndrome, whose signs may overlap with RSTS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20125191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 377, "text": "At molecular level, MWS is characterized by many different described mutations in the zinc finger E-box protein 2 (ZEB2) gene, ultimately leading to loss of gene function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24092421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Individuals with Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene rarely diagnosed prenatally and with little fetal description reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 354, "text": "MWS is caused by de novo heterozygous mutations in the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "endSection": "abstract" } ] }, { "body": "How is active neurotoxin of Clostridium botulinum detected?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23925142", "http://www.ncbi.nlm.nih.gov/pubmed/22223483", "http://www.ncbi.nlm.nih.gov/pubmed/18571757", "http://www.ncbi.nlm.nih.gov/pubmed/7989542", "http://www.ncbi.nlm.nih.gov/pubmed/23518650", "http://www.ncbi.nlm.nih.gov/pubmed/16318699", "http://www.ncbi.nlm.nih.gov/pubmed/23181535", "http://www.ncbi.nlm.nih.gov/pubmed/23239357", "http://www.ncbi.nlm.nih.gov/pubmed/16614251" ], "ideal_answer": [ "Active neurotoxin of Clostridium botulinum can be detected by:\nmouse lethality assay\nby mass spectrometry\nbioassay\ndifferentiated cell models\npeptide cleavage assay\nFDC (functional dual coating) microtitre plate immuno-biochemical assay\nendopeptidase activity monitored via UV-Visible spectroscopy" ], "exact_answer": [ [ "mouse lethality assay" ], [ "by mass spectrometry" ], [ "bioassay" ], [ "differentiated cell models" ], [ "peptide cleavage assay" ], [ "FDC (functional dual coating) microtitre plate immuno-biochemical assay" ], [ "endopeptidase activity monitored via UV-Visible spectroscopy" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009498", "http://www.disease-ontology.org/api/metadata/DOID:11976", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0014865", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019274", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042241", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010061", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003014", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009405", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003013", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001905" ], "type": "list", "id": "531d6bfc267d7dd053000007", "snippets": [ { "offsetInBeginSection": 513, "offsetInEndSection": 577, "text": "The neurotoxin detection is based on the mouse lethality assay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16614251", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 841, "text": "which could be shown by bioassay to produce biologically active type B toxin in culture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7989542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Human induced pluripotent stem cells (hiPSC) hold great promise for providing various differentiated cell models for in vitro toxigenicity testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1535, "text": "A direct comparison of BoNT detection using primary rat spinal cord cells and hiPSC-derived neurons showed equal or increased sensitivity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1218, "text": "BoNT/A intoxication studies demonstrate that the hiPSC-derived neurons reproducibly and quantitatively detect biologically active BoNT/A with high sensitivity (EC(50) \u223c0.3 U).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483", "endSection": "abstract" }, { "offsetInBeginSection": 1655, "offsetInEndSection": 1847, "text": " these data suggest that neurons derived from hiPSCs provide an ideal and highly sensitive platform for BoNT potency determination, neutralizing antibody detection and for mechanistic studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Detection of botulinum neurotoxin-A activity in food by peptide cleavage assay.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18571757", "endSection": "title" }, { "offsetInBeginSection": 354, "offsetInEndSection": 535, "text": "his study reports the successful use of an enzymatic assay employing an internally quenched fluorogenic peptide as a fast, simple and inexpensive alternative to the mouse bioassay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18571757", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 537, "text": "BoNT endopeptidase assays", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23181535", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 797, "text": "in vivo mouse bioassay has for years been the 'gold standard' assay used for this purpose", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23239357", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1073, "text": "Cell-based assays are currently the only in vitro alternative that detect fully functional BoNTs in a single assay and have been utilized for years for research purposes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23239357", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 514, "text": "mouse bioassay (MBA) is traditionally used to confirm the presence of toxin in serum or food", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23518650", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 705, "text": "A novel FDC (functional dual coating) microtitre plate immuno-biochemical assay,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23518650", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 762, "text": "This report demonstrates a novel assay that utilises the endopeptidase activity of the toxin to detect Botulinum neurotoxin in a pharmaceutical sample. The cleaving of SNAP-25 is monitored via UV-Visible spectroscopy with a limit of detection of 373 fg/mL and has been further developed into a high throughput method using a microplate reader detecting down to 600 fg/mL of active toxin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23925142", "endSection": "abstract" } ] }, { "body": "Which factor interacts with Treslin/TICRR throughout the cell cycle of human cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23704573" ], "ideal_answer": [ "MDM two binding protein (MTBP) is a factor that interacts with Treslin/TICRR throughout the cell cycle. MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, it is required for DNA replication irrespective of a cell's p53 status. MTBP is proposed to act with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells." ], "exact_answer": [ "MDM two binding protein (MTBP)" ], "concepts": [ "http://www.uniprot.org/uniprot/TICRR_XENLA", "http://www.uniprot.org/uniprot/TICRR_MOUSE", "http://www.uniprot.org/uniprot/TICRR_DANRE", "http://www.uniprot.org/uniprot/TICRR_HUMAN" ], "type": "factoid", "id": "56d19a363975bb303a000017", "snippets": [ { "offsetInBeginSection": 289, "offsetInEndSection": 917, "text": "We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle. We show that MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, we found MTBP is required for DNA replication irrespective of a cell's p53 status. We propose that MTBP acts with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704573", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 405, "text": "We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 407, "text": "Treslin/TICRR (TopBP1-interacting, replication stimulating protein/TopBP1-interacting, checkpoint, and replication regulator), the human ortholog of the yeast Sld3 protein, is an essential DNA replication factor that is regulated by cyclin-dependent kinases and the DNA damage checkpoint. We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704573", "endSection": "abstract" } ] }, { "body": "What is oprozomib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "http://www.ncbi.nlm.nih.gov/pubmed/24135407", "http://www.ncbi.nlm.nih.gov/pubmed/22929803", "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "http://www.ncbi.nlm.nih.gov/pubmed/24239172", "http://www.ncbi.nlm.nih.gov/pubmed/25935605", "http://www.ncbi.nlm.nih.gov/pubmed/25005844", "http://www.ncbi.nlm.nih.gov/pubmed/22995770" ], "ideal_answer": [ "Oprozomib is a second-generation, highly-selective, orally administered proteasome inhibitor with promising activity against multiple myeloma.\nOprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. Consequently, oprozomib seems to be able to effectively shift the bone microenvironment from a catabolic to an anabolic state and, similar to bortezomib, may decrease skeletal complications of MM.\nOprozomib effectively decreases multiple myeloma cell viability.\nOprozomib potently inhibit cell survival and induce apoptosis in HNSCC cell lines via upregulation of pro-apoptotic Bik. Upregulation of Mcl-1 by these agents served to dampen their efficacies. Oprozomib also induced autophagy, mediated, in part, by activation of the UPR pathway involving upregulation of ATF4 transcription factor. Autophagy induction served a prosurvival role. Oral administration of ONX 0912 inhibited the growth of HNSCC xenograft tumors in a dose-dependent manner.\nOprozomib inhibited NF-\u03baB expression." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061988" ], "type": "summary", "id": "56ecffd62ac5ed1459000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803", "endSection": "title" }, { "offsetInBeginSection": 162, "offsetInEndSection": 221, "text": "ONX 0912 (oprozomib) is an orally bioavailable derivative. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1356, "text": "Carfilzomib and ONX 0912 potently induced apoptosis in HNSCC cell lines via upregulation of pro-apoptotic Bik. Upregulation of Mcl-1 by these agents served to dampen their efficacies. Carfilzomib and ONX 0912 also induced autophagy, mediated, in part, by activation of the UPR pathway involving upregulation of ATF4 transcription factor. Autophagy induction served a prosurvival role. Oral administration of ONX 0912 inhibited the growth of HNSCC xenograft tumors in a dose-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803", "endSection": "abstract" }, { "offsetInBeginSection": 1369, "offsetInEndSection": 1689, "text": "These results show that carfilzomib and ONX 0912 are potently active against HNSCC cells, and the activities of these agents can be enhanced via suppression of Mcl-1 or inhibition of autophagy. Oral ONX 0912 exhibits in vivo activity against HNSCC tumors and may represent a useful therapeutic agent for this malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22929803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "title" }, { "offsetInBeginSection": 383, "offsetInEndSection": 1276, "text": "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors. Both compounds promote upregulation of proapoptotic BIK and antiapoptotic MCL1, which serves to mediate and attenuate, respectively, the killing activities of these proteasome inhibitors. Both compounds also induce complete autophagic flux that is partially dependent on activation of the unfolded protein response (UPR) and upregulation of ATF4. Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell survival. Our study indicates that the therapeutic benefit of these promising proteasome inhibitors may be improved by inhibiting MCL1 expression or autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 543, "text": "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 1547, "text": "At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. Finally, in mouse models of disseminated MM, the epoxyketone-based PIs decreased murine 5TGM1 and human RPMI-8226 tumor burden and prevented bone loss. These data demonstrate that, in addition to anti-myeloma properties, carfilzomib and oprozomib effectively shift the bone microenvironment from a catabolic to an anabolic state and, similar to bortezomib, may decrease skeletal complications of MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1234, "text": "Finally, we found that DC incubation with the drug(s) enhanced I\u03baB expression and that oprozomib inhibited NF-\u03baB expression. We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Carfilzomib and oprozomib synergize with histone deacetylase inhibitors in head and neck squamous cell carcinoma models of acquired resistance to proteasome inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "title" }, { "offsetInBeginSection": 123, "offsetInEndSection": 254, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1071, "text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1200, "text": "Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 882, "text": "Further, new orally administered second-generation PI oprozomib is being investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 384, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1295, "text": "Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 716, "text": "Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1209, "text": "Finally, we found that DC incubation with the drug(s) enhanced I\u03baB expression and that oprozomib inhibited NF-\u03baB expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 787, "text": "Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "title" }, { "offsetInBeginSection": 715, "offsetInEndSection": 800, "text": "Further, new orally administered second-generation PI oprozomib is being investigated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1070, "text": "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "title" }, { "offsetInBeginSection": 383, "offsetInEndSection": 698, "text": "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1148, "text": "Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 994, "text": "At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 698, "text": "Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 255, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1127, "text": "Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 428, "text": "Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24915039", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1234, "text": "Finally, we found that DC incubation with the drug(s) enhanced I\u03baB expression and that oprozomib inhibited NF-\u03baB expression. We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24103732", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1148, "text": "At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763387", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 698, "text": "We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995770", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 707, "text": "Next generation proteasome inhibitors include carfilzomib and oprozomib which are irreversible epoxyketone proteasome inhibitors; and ixazomib and delanzomib which are reversible boronic acid proteasome inhibitors. Two proteasome inhibitors, bortezomib and carfilzomib are FDA approved drugs and ixazomib and oprozomib are in late stage clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25935605", "endSection": "abstract" } ] }, { "body": "Is there a relationship between junctin and ryanodine receptors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19230141", "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "http://www.ncbi.nlm.nih.gov/pubmed/24257462", "http://www.ncbi.nlm.nih.gov/pubmed/19448693", "http://www.ncbi.nlm.nih.gov/pubmed/11162129", "http://www.ncbi.nlm.nih.gov/pubmed/19398037" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400276", "o": "C498842" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1454076", "o": "http://linkedlifedata.com/resource/umls/label/A8400276" }, { "p": 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normally acts as an activator of RyR channels at low luminal [Ca(2+)], and as an inhibitor at high luminal [Ca(2+)]." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/RYR1_RABIT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019837", "http://www.uniprot.org/uniprot/RYR3_MOUSE", "http://www.uniprot.org/uniprot/RYR2_RABIT", "http://www.uniprot.org/uniprot/RYR2_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005219", "http://www.uniprot.org/uniprot/RYR1_RAT", "http://www.uniprot.org/uniprot/RYR2_RAT", "http://www.uniprot.org/uniprot/RYR1_HUMAN", "http://www.uniprot.org/uniprot/RYR1_PIG", "http://www.uniprot.org/uniprot/RYR3_HUMAN", "http://www.uniprot.org/uniprot/RYR2_HUMAN", "http://www.uniprot.org/uniprot/RYR1_MOUSE", "http://www.uniprot.org/uniprot/RYR3_RABIT" ], "type": "yesno", "id": "52b2f3b74003448f5500000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Junctin, a 26 kDa intra-sarcoplasmic reticulum (SR) protein, forms a quaternary complex with triadin, calsequestrin and the ryanodine receptor (RyR) at the junctional SR membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 919, "text": "Junctin ablation appears to affect how RyRs 'sense' SR Ca(2+) load, resulting in decreased diastolic SR Ca(2+) leak despite an elevated [Ca(2+)](SR). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1804, "text": "Single channel recordings of RyRs from WT and JCN-KO cardiac SR indicate that the absence of junctin produces a dual effect on the normally linear response of RyRs to luminal [Ca(2+)]: at low luminal [Ca(2+)] (<1 mmol l(-1)), junctin-devoid RyR channels are less responsive to luminal [Ca(2+)]; conversely, high luminal [Ca(2+)] turns them hypersensitive to this form of channel modulation. Thus, junctin produces complex effects on Ca(2+) sparks, transients, and leak, but the luminal [Ca(2+)]-dependent dual response of junctin-devoid RyRs demonstrates that junctin normally acts as an activator of RyR channels at low luminal [Ca(2+)], and as an inhibitor at high luminal [Ca(2+)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Normal Ca(2+) signalling in skeletal muscle depends on the membrane associated proteins triadin and junctin and their ability to mediate functional interactions between the Ca(2+) binding protein calsequestrin and the type 1 ryanodine receptor in the lumen of the sarcoplasmic reticulum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398037", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 1212, "text": "We show here that purified skeletal ryanodine receptors are similarly activated by purified triadin or purified junctin added to their luminal side, although a lack of competition indicated that the proteins act at independent sites. Surprisingly, triadin and junctin differed markedly in their ability to transmit information between skeletal calsequestrin and ryanodine receptors. Purified calsequestrin inhibited junctin/triadin-associated, or junctin-associated, ryanodine receptors and the calsequestrin re-associated channel complexes were further inhibited when luminal Ca(2+) fell from 1mM to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398037", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 797, "text": "By fusing GCaMP6f to the N-terminus of triadin 1 or junctin, GCaMP6f-T/J was targeted to dyadic junctions, where it colocalized with t-tubules and RyRs after adenovirus-mediated gene transfer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257462", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 532, "text": "The junctional face of the jSR, facing the transverse tubules, is occupied by a molecular complex composed of the transmembrane Ca2+ release channels (ryanodine receptors); the luminal protein calsequestrin (CSQ); the 2 membrane proteins, junctin (Jct), and triadin (Tr), which mediate CSQ-ryanodine receptor interactions; and several other components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19448693", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 581, "text": "Calsequestrin, the main calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for release through the ryanodine receptor and acts as a luminal calcium sensor for the channel via its interactions with triadin and junctin. We examined the influence of phosphorylation of calsequestrin on its ability to store calcium, to polymerise and to regulate ryanodine receptors by binding to triadin and junctin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19230141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Junctin is a 26 kDa membrane protein that binds to calsequestrin, triadin, and ryanodine receptors (RyRs) within the junctional sarcoplasmic reticulum of calcium release units. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11162129", "endSection": "abstract" } ] }, { "body": "Which medication should be administered when managing patients with suspected acute opioid overdose?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9562190", "http://www.ncbi.nlm.nih.gov/pubmed/8907145", "http://www.ncbi.nlm.nih.gov/pubmed/11130352", "http://www.ncbi.nlm.nih.gov/pubmed/11015242", "http://www.ncbi.nlm.nih.gov/pubmed/1470965", "http://www.ncbi.nlm.nih.gov/pubmed/21044832", "http://www.ncbi.nlm.nih.gov/pubmed/17849242" ], "ideal_answer": [ "Naloxone is opioid anagonist that should be administered for all patients with suspected acute opioid overdose. Intravenous naltrexone hydrochloride is usually administered, however, other formulations, including enteral methylnaltrexone, nebulized naloxone and subcutaneous naloxone, are under investigation and can be used under certain circumstances." ], "exact_answer": [ "naloxone" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062787", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000701", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009292" ], "type": "factoid", "id": "5149f494d24251bc0500004c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 145, "text": "Opioid overdose has a high mortality, but is often reversible with appropriate overdose management and naloxone (opioid antagonist). ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21044832", "endSection": "sections.0" }, { "offsetInBeginSection": 1691, "offsetInEndSection": 1782, "text": "Training clinicians how to manage an opioid overdose and administer naloxone was effective.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21044832", "endSection": "sections.0" }, { "offsetInBeginSection": 2841, "offsetInEndSection": 3085, "text": "For patients who have ingested dextromethorphan and are sedated or comatose, naloxone, in the usual doses for treatment of opioid overdose, can be considered for prehospital administration, particularly if the patient has respiratory depression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17849242", "endSection": "sections.0" }, { "offsetInBeginSection": 200, "offsetInEndSection": 394, "text": "Naloxone hydrochloride, an injectable opioid antagonist which reverses the respiratory depression, sedation and hypotension associated with opioids, has long been used to treat opioid overdose. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11130352", "endSection": "sections.0" }, { "offsetInBeginSection": 394, "offsetInEndSection": 567, "text": "Experts have suggested that, as part of a comprehensive overdose prevention strategy, naloxone should be provided to heroin users for peer administration after an overdose. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11130352", "endSection": "sections.0" }, { "offsetInBeginSection": 184, "offsetInEndSection": 336, "text": "Patients who received naloxone for known or presumed opioid overdose were formally evaluated one hour later for multiple potential predictor variables. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11015242", "endSection": "sections.0" }, { "offsetInBeginSection": 741, "offsetInEndSection": 843, "text": "Patients with presumed opioid overdose can be safely discharged one hour after naloxone administration", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11015242", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 202, "text": "To determine whether naloxone administered i.v. to out-of-hospital patients with suspected opioid overdose would have a more rapid therapeutic onset than naloxone given subcutaneously (s.q.).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9562190", "endSection": "sections.0" }, { "offsetInBeginSection": 540, "offsetInEndSection": 677, "text": "Subjects received either naloxone 0.4 mg i.v. (n = 74) or naloxone 0.8 mg s.q. (n = 122), for respiratory depression of <10 breaths/min. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9562190", "endSection": "sections.0" }, { "offsetInBeginSection": 1143, "offsetInEndSection": 1371, "text": "There was no clinical difference in the time interval to respiratory rate > or =10 breaths/min between naloxone 0.8 mg s.q. and naloxone 0.4 mg i.v. for the out-of-hospital management of patients with suspected opioid overdose. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9562190", "endSection": "sections.0" }, { "offsetInBeginSection": 243, "offsetInEndSection": 518, "text": "To illustrate this problem, we report the case of a patient inappropriately treated with naloxone and the results of a retrospective review of the medical records of 15 consecutive patients with cancer treated with naloxone in the emergency department over a 5-month period. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8907145", "endSection": "sections.0" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1360, "text": "Management of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid antagonists. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1470965", "endSection": "sections.0" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1677, "text": " The proportion of clinicians willing to use naloxone in an opioid overdose rose from 77% to 99% after training. Barriers to implementing training were clinician time and confidence, service resources, client willingness and naloxone formulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21044832", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Opioid overdose is rarely the primary cause of altered mental status in cancer patients receiving opioid therapy. The inappropriate administration of naloxone to reverse an abnormal mental status can cause severe withdrawal symptoms and pain. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8907145", "endSection": "sections.0" } ] }, { "body": "In which nuclear compartments is heterochromatin located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23834025", "http://www.ncbi.nlm.nih.gov/pubmed/16254244", "http://www.ncbi.nlm.nih.gov/pubmed/12432450", "http://www.ncbi.nlm.nih.gov/pubmed/22251972", "http://www.ncbi.nlm.nih.gov/pubmed/20026667", "http://www.ncbi.nlm.nih.gov/pubmed/21283637", "http://www.ncbi.nlm.nih.gov/pubmed/19889207", "http://www.ncbi.nlm.nih.gov/pubmed/15564378" ], "ideal_answer": [ "This compartment localizes into three main regions: the peripheral heterochromatin, perinucleolar heterochromatin, and pericentromeric heterochromatin. Silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3), DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modification" ], "exact_answer": [ [ "peripheral heterochromatin" ], [ "perinucleolar heterochromatin" ], [ "pericentromeric heterochromatin" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0051276", "http://amigo.geneontology.org/amigo/term/GO:0070828", "http://amigo.geneontology.org/amigo/term/GO:0000785", "http://amigo.geneontology.org/amigo/term/GO:0000792", "http://amigo.geneontology.org/amigo/term/GO:0031507", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006570", "http://amigo.geneontology.org/amigo/term/GO:0005720" ], "type": "list", "id": "56c33e5695c1e7cc5b000001", "snippets": [ { "offsetInBeginSection": 260, "offsetInEndSection": 410, "text": "This compartment localizes into three main regions: the peripheral heterochromatin, perinucleolar heterochromatin, and pericentromeric heterochromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23834025", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 967, "text": "By separating cells according to transgene expression we show here that silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3), DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modifications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19889207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The cell nucleus is divided into chromosome territories and the extrachromosomal domain. The latter includes several structural and functional compartments involved in RNA processing and transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12432450", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1001, "text": "We also describe a new apocentric nuclear compartment with a unique set of histone modifications that occurs as a zone of chromatin surrounding centromeric heterochromatin in differentiated lymphocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15564378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Little is known about the mechanisms of gene targeting within the nucleus and its effect on gene expression, but most studies have concluded that genes located near the nuclear periphery are silenced by heterochromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22251972", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1129, "text": "After TSA and NaBt treatment, the HP1 proteins were repositioned more internally in the nucleus, being closely associated with interchromatin compartments, while centromeric heterochromatin was relocated closer to the nuclear periphery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254244", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 850, "text": "Taking into account the different heterochromatic and euchromatic compartments of the genome, our data suggest that the relative abundance of Ty3/gypsy LTRrs along each chromosome arm is determined mainly by the different proportions of heterochromatin, particularly pericentric heterochromatin, relative to total arm length", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21283637", "endSection": "abstract" } ] }, { "body": "Have mutations in the ZEB2 gene been found in any human syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "http://www.ncbi.nlm.nih.gov/pubmed/23243526", "http://www.ncbi.nlm.nih.gov/pubmed/24029077", "http://www.ncbi.nlm.nih.gov/pubmed/16150342", "http://www.ncbi.nlm.nih.gov/pubmed/18445050", "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "http://www.ncbi.nlm.nih.gov/pubmed/23322667", "http://www.ncbi.nlm.nih.gov/pubmed/16053902", "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "http://www.ncbi.nlm.nih.gov/pubmed/19215041", "http://www.ncbi.nlm.nih.gov/pubmed/16688751", "http://www.ncbi.nlm.nih.gov/pubmed/23001561", "http://www.ncbi.nlm.nih.gov/pubmed/22246645", "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "http://www.ncbi.nlm.nih.gov/pubmed/23152852", "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "http://www.ncbi.nlm.nih.gov/pubmed/17932455", "http://www.ncbi.nlm.nih.gov/pubmed/20093881", "http://www.ncbi.nlm.nih.gov/pubmed/18259761", "http://www.ncbi.nlm.nih.gov/pubmed/15006694", "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "http://www.ncbi.nlm.nih.gov/pubmed/23312518", "http://www.ncbi.nlm.nih.gov/pubmed/18230842", "http://www.ncbi.nlm.nih.gov/pubmed/12746390", "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "http://www.ncbi.nlm.nih.gov/pubmed/20125191", "http://www.ncbi.nlm.nih.gov/pubmed/16088920", "http://www.ncbi.nlm.nih.gov/pubmed/17223398", "http://www.ncbi.nlm.nih.gov/pubmed/20145308", "http://www.ncbi.nlm.nih.gov/pubmed/16532472", "http://www.ncbi.nlm.nih.gov/pubmed/19236961" ], "ideal_answer": [ "Yes, the Mowat-Wilson syndrome" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/ZEB2_HUMAN", "http://www.uniprot.org/uniprot/ZEB2_MOUSE" ], "type": "yesno", "id": "53552ed7f1005d6b58000001", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 156, "text": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282181", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 233, "text": "Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029077", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 111, "text": "owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523603", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 354, "text": "MWS is caused by de novo heterozygous mutations in the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466526", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 274, "text": "The cause of MWS is a de novo mutation in the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427518", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 111, "text": "owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322667", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 691, "text": "MWS have a heterozygous loss-of-function mutation in the zinc finger E-box protein 2 (ZEB2) gene, also called SIP1 (Smad-interacting protein 1) and ZFHX1B,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23243526", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 974, "text": " human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152852", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 215, "text": "Mutations at the hZeb2 locus cause Mowat-Wilson syndrome (MWS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001561", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 76, "text": "Mowat-Wilson syndrome and a mutation in ZEB2", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486326", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 93, "text": "owat-Wilson syndrome (MWS) is caused by a heterozygous mutation or deletion of the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246645", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 397, "text": "The syndrome is caused by mutations or deletions of the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 85, "text": "owat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893004", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 710, "text": "single-copy ZEB2 gene deletion at 2q22.3 consistent with Mowat-Wilson syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20093881", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 305, "text": "Mowat-Wilson syndrome, confirmed by molecular analysis as a heterozygous deletion of the ZEB2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20145308", "endSection": "abstract" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1084, "text": "deletion encompassing ZEB2, the gene responsible for the Mowat-Wilson syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20125191", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1082, "text": " Six patients had deletions in the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 58, "text": "ZEB2 gene analysis for Mowat-Wilson syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842203", "endSection": "title" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1257, "text": "Mowat-Wilson syndrome (MWS) like appearance was noted. The disease is caused by mutation or deletion of ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19236961", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 127, "text": "owat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19215041", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 185, "text": "owat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder with mental retardation and variable multiple congenital abnormalities due to mutations of the ZEB2 (ZFHX1B) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18445050", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1071, "text": "MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17958891", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 153, "text": "owat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932455", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 778, "text": "the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17223398", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 435, "text": "de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 113, "text": "owat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 55, "text": "FHX1B mutations in patients with Mowat-Wilson syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17203459", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 390, "text": "Mutations leading to haploinsufficiency of the ZFHX1B gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 98, "text": "mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16688751", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 69, "text": "ZFHX1B mutation associated with a mild Mowat-Wilson syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16532472", "endSection": "title" }, { "offsetInBeginSection": 20, "offsetInEndSection": 197, "text": "Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16150342", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 441, "text": "Heterozygous mutations or deletions involving the gene ZFHX1B (previously SIP1) [OMIM 605802] have recently been found to cause MWS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16088920", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 680, "text": " ZFHX1B deletions, splice site or truncating mutations were detected in all 28 patients classified as typical MWS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16053902", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 117, "text": "Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "endSection": "title" }, { "offsetInBeginSection": 437, "offsetInEndSection": 499, "text": " mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15908750", "endSection": "abstract" }, { "offsetInBeginSection": 38, "offsetInEndSection": 172, "text": "ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the \"Mowat-Wilson\" syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 287, "text": " ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006694", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 118, "text": "mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14681759", "endSection": "title" }, { "offsetInBeginSection": 474, "offsetInEndSection": 572, "text": "syndrome is the result of heterozygous deletions or truncating mutations of the ZFHX1B (SIP1) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12746390", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 737, "text": "humans with Zfhx1b mutations (Mowat-Wilson syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312518", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 665, "text": "syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 72, "text": "owat-Wilson syndrome (MWS) is a recently delineated mental retardation;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428734", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 126, "text": "Mowat-Wilson syndrome is a congenital syndrome caused by a defect of the transcriptional repressor ZFHX1B (SIP1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18259761", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 537, "text": "Mowat-Wilson syndrome patients, and all siblings had the same E87X nonsense mutation in ZFHX1B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18230842", "endSection": "abstract" } ] }, { "body": "Which enzymes are involved in global genome nucleotide excision repair (GG-NER) in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20004108", "http://www.ncbi.nlm.nih.gov/pubmed/19617358", "http://www.ncbi.nlm.nih.gov/pubmed/19933360", "http://www.ncbi.nlm.nih.gov/pubmed/24290807", "http://www.ncbi.nlm.nih.gov/pubmed/23963890", "http://www.ncbi.nlm.nih.gov/pubmed/23245695", "http://www.ncbi.nlm.nih.gov/pubmed/21145481", "http://www.ncbi.nlm.nih.gov/pubmed/19762288", "http://www.ncbi.nlm.nih.gov/pubmed/22559785", "http://www.ncbi.nlm.nih.gov/pubmed/25463394" ], "ideal_answer": [ "Nucleotide excision repair (NER) is universally used to recognize and remove many types of DNA damage. In eubacteria, the NER system typically consists of UvrA, UvrB, UvrC, the UvrD helicase, DNA polymerase I, and ligase. Damage recognition during bacterial NER depends upon UvrA, which binds to the damage and loads UvrB onto the DNA. Subsequently, UvrA, UvrB and UvrC form the excinuclease protein UvrABC endonuclease, a multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. In some cases, Cho may be the effective nuclease for NER, rather than UvrC. UvrC nuclease and the short oligonucleotide that contains the DNA lesion are removed from the post-incision complex by UvrD, a superfamily 1A helicase. In gram-positive organisms, PcrA helicase can also displace UvrC and the excised oligonucleotide from a post-incision NER complex." ], "exact_answer": [ [ "UvrA" ], [ "UvrB" ], [ "UvrC nuclease" ], [ "UvrD 1A helicase" ], [ "DNA polymerase I" ], [ "Ligase" ], [ "Cho nuclease (instead of UvrC)" ], [ "PcrA helicase (instead of Uvrd, in gram-positive bacteria)" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000720", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000109", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006289", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070911", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260" ], "type": "list", "id": "5547a7e9f35db75526000006", "snippets": [ { "offsetInBeginSection": 169, "offsetInEndSection": 455, "text": "we evaluated the in vivo role of NER in the repair of DNA adducts generated by psoralens (mono- or bi-functional) and UV-A light (PUVA) in E. coli. Cultures of wild-type E. coli K12 and mutants for uvrA, uvrB, uvrC or uvrAC genes were treated with PUVA and cell survival was determined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20004108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Nucleotide excision repair (NER) is universally used to recognize and remove many types of DNA damage. In eubacteria, the NER system typically consists of UvrA, UvrB, UvrC, the UvrD helicase, DNA polymerase I, and ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "During nucleotide excision repair (NER) in bacteria the UvrC nuclease and the short oligonucleotide that contains the DNA lesion are removed from the post-incision complex by UvrD, a superfamily 1A helicase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19762288", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 416, "text": "UvrD interacts with UvrB, a component of the post-incision complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19762288", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1400, "text": "PcrA helicase from Bacillus stearothermophilus can also displace UvrC and the excised oligonucleotide from a post-incision NER complex, which supports the idea that PcrA performs a UvrD-like function during NER in gram-positive organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19762288", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1032, "text": "Cho rather than UvrC seems to be an effective nuclease for the NER of DPCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19617358", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 478, "text": "Nucleotide excision repair consists of excinuclease protein UvrABC endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in sequential manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23963890", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 502, "text": "Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23245695", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 1194, "text": "we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H. pylori mutation and recombination. RESULTS: Inactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase) into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22559785", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 586, "text": "Transcription-coupled DNA repair (TCR) is a subpathway of nucleotide excision repair (NER) that is triggered when RNA polymerase is stalled by DNA damage. Lesions targeted by TCR are repaired more quickly than lesions repaired by the transcription-independent \"global\" NER pathway, but the mechanism underlying this rate enhancement is not understood. Damage recognition during bacterial NER depends upon UvrA, which binds to the damage and loads UvrB onto the DNA. Bacterial TCR additionally requires the Mfd protein, a DNA translocase that removes the stalled transcription complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21145481", "endSection": "abstract" } ] }, { "body": "Is JTV519 (K201) a potential drug for the prevention of arrhythmias?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20581784", "http://www.ncbi.nlm.nih.gov/pubmed/15584870", "http://www.ncbi.nlm.nih.gov/pubmed/16825580", "http://www.ncbi.nlm.nih.gov/pubmed/21291389", "http://www.ncbi.nlm.nih.gov/pubmed/22001562", "http://www.ncbi.nlm.nih.gov/pubmed/23144205", "http://www.ncbi.nlm.nih.gov/pubmed/22563249", "http://www.ncbi.nlm.nih.gov/pubmed/20080988", "http://www.ncbi.nlm.nih.gov/pubmed/17644079", "http://www.ncbi.nlm.nih.gov/pubmed/15073377", "http://www.ncbi.nlm.nih.gov/pubmed/17994112", "http://www.ncbi.nlm.nih.gov/pubmed/11090108", "http://www.ncbi.nlm.nih.gov/pubmed/12890053", "http://www.ncbi.nlm.nih.gov/pubmed/16672364", "http://www.ncbi.nlm.nih.gov/pubmed/16185151" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16995906", "o": "C109183" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17004235", "o": "JTV-519" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0754680", "o": "http://linkedlifedata.com/resource/umls/label/A7798511" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0754680", "o": "http://linkedlifedata.com/resource/umls/label/A17004235" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7798511", "o": "JTV519" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0754680", "o": "http://linkedlifedata.com/resource/umls/label/A16995906" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16995906", "o": "JTV 519" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0754680", "o": "http://linkedlifedata.com/resource/umls/label/A7798511" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17004235", "o": "C109183" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7798511", "o": "C109183" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16995906", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17004235", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7798511", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C0754680", "o": "http://linkedlifedata.com/resource/umls/id/C0668089" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1334561", "o": "K-201" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1362694", "o": "K201 compound" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0668089", "o": "http://linkedlifedata.com/resource/umls/id/C0754680" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C0754680", "o": "http://linkedlifedata.com/resource/umls/relation/R32009562" }, { "p": "http://www.w3.org/2004/02/skos/core#inScheme", "s": "http://linkedlifedata.com/resource/umls/id/C0754680", "o": "http://linkedlifedata.com/resource/umls" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R32161252", "o": "http://linkedlifedata.com/resource/umls/id/C0754680" } ], "ideal_answer": [ "Yes, JTV519 has antiarrhythmic properties." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000889" ], "type": "yesno", "id": "52b2f1724003448f5500000b", "snippets": [ { "offsetInBeginSection": 330, "offsetInEndSection": 636, "text": "We compared the suppressive effect of K201 (JTV519), a multiple-channel blocker and cardiac ryanodine receptor-calcium release channel (RyR2) stabilizer, with that of diltiazem, a Ca(2+ )channel blocker, in 2 studies of isoproterenol-induced (n = 30) and ischemic-reperfusion-induced VAs (n = 38) in rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144205", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1584, "text": "After administration of isoproterenol under Ca(2+) loading, fatal VA frequently occurred in the vehicle (9 of 10 animals, 90%) and diltiazem (8 of 10, 80%) groups, and K201 significantly suppressed the incidences of arrhythmia and mortality (2 of 10, 20%). In the reperfusion study, the incidence and the time until occurrence of reperfusion-induced VA and mortality were significantly suppressed in the K201 (2 of 15 animals, 13%) and diltiazem (1 of 9 animals, 11%) groups compared to the vehicle group (8 of 14 animals, 57%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144205", "endSection": "abstract" }, { "offsetInBeginSection": 1707, "offsetInEndSection": 1860, "text": "K201 markedly suppressed both the isoproterenol-induced and the reperfusion-induced VAs, whereas diltiazem did not suppress the isoproterenol-induced VA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144205", "endSection": "abstract" }, { "offsetInBeginSection": 1614, "offsetInEndSection": 1876, "text": "JTV519 (K201) is a newly developed 1,4-benzothiazepine drug with antiarrhythmic and cardioprotective properties. It appears to be very effective in not only preventing but also in reversing the characteristic myocardial changes and preventing lethal arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22563249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "The novel antiarrhythmic drug K201 (4-[3-{1-(4-benzyl)piperidinyl}propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine monohydrochloride) is currently in development for treatment of atrial fibrillation. K201 not only controls intracellular calcium release by the ryanodine receptors, but also possesses a ventricular action that might predispose to torsade de pointes arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22001562", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1152, "text": "The RyR is currently used as a therapeutic target in malignant hyperthermia where dantrolene is effective and to relieve ventricular arrhythmia, with the use of JTV519 and flecainide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21291389", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1372, "text": "Finally, KN-3 and JTV519, two compounds that stabilize RyR2 in the closed state, prevent the induction of triggered activity and suppress the inducibility of sustained AF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581784", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1718, "text": "JTV-519 greatly reduced the frequency of ouabain-induced arrhythmogenic events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080988", "endSection": "abstract" }, { "offsetInBeginSection": 1914, "offsetInEndSection": 1995, "text": "Stabilization of RyR2 by JTV-519 effectively reduces these triggered arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080988", "endSection": "abstract" }, { "offsetInBeginSection": 1473, "offsetInEndSection": 1537, "text": "These findings may reveal the anti-arrhythmic potential of K201.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17994112", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 340, "text": "The preferential ryanodine receptor stabilizer (K201) possesses antiarrhythmic effects through calcium regulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17994112", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 153, "text": "The drug K201 (JTV-519) increases inotropy and suppresses arrhythmias in failing hearts, but the effects of K201 on normal hearts is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644079", "endSection": "abstract" }, { "offsetInBeginSection": 1510, "offsetInEndSection": 1616, "text": "K201 fails to prevent DADs in RyR2(R4496C+/-) myocytes and ventricular arrhythmias in RyR2(R4496C+/-) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16825580", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1198, "text": "In vivo administration of K201 failed to prevent induction of polymorphic ventricular tachycardia (VT) in RyR2(R4496C+/-) mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16825580", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1089, "text": "The 1,4-benzothiazepine JTV519, which increases the binding affinity of calstabin-2 for RyR2, inhibited the diastolic SR Ca2+ leak, monophasic action potential alternans and triggered arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16672364", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 720, "text": "In arrhythmias, the calstabin2 stabiliser JTV519 did not prevent arrhythmias in calstabin2-/- mice, but reduced the arrhythmias in calstabin2+/- mice, illustrating the antiarrhythmic potential of stabilising calstablin2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16185151", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 652, "text": "In three models of arrhythmias, the calstabin2 stabiliser JTV519 did not prevent arrhythmias in calstabin2(-/-) mice, but reduced the arrhythmias in calstabin2(+/-) mice, illustrating the antiarrhythmic potential of stabilising calstabin2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15584870", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 645, "text": "A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak that triggers arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15073377", "endSection": "abstract" }, { "offsetInBeginSection": 1480, "offsetInEndSection": 1732, "text": "JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12890053", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1002, "text": "JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2 +/- 2.9 to 0 +/- 0, P < 0.01). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12890053", "endSection": "abstract" }, { "offsetInBeginSection": 1652, "offsetInEndSection": 1851, "text": "We conclude that JTV-519 can exert antiarrhythmic effects against AF by inhibiting repolarizing K(+) currents. The drug may be useful for the treatment of AF in patients with ischaemic heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11090108", "endSection": "abstract" } ] }, { "body": "What is the mechanism of microRNA deregulation in carcinogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23087084", "http://www.ncbi.nlm.nih.gov/pubmed/22293089", "http://www.ncbi.nlm.nih.gov/pubmed/23509776", "http://www.ncbi.nlm.nih.gov/pubmed/22303357", "http://www.ncbi.nlm.nih.gov/pubmed/18700954", "http://www.ncbi.nlm.nih.gov/pubmed/19664288", "http://www.ncbi.nlm.nih.gov/pubmed/19912656", "http://www.ncbi.nlm.nih.gov/pubmed/19440243", "http://www.ncbi.nlm.nih.gov/pubmed/23071542", "http://www.ncbi.nlm.nih.gov/pubmed/22912875", "http://www.ncbi.nlm.nih.gov/pubmed/22898998", "http://www.ncbi.nlm.nih.gov/pubmed/23293655", "http://www.ncbi.nlm.nih.gov/pubmed/22583478", "http://www.ncbi.nlm.nih.gov/pubmed/23074383", "http://www.ncbi.nlm.nih.gov/pubmed/23064433", "http://www.ncbi.nlm.nih.gov/pubmed/18040713", "http://www.ncbi.nlm.nih.gov/pubmed/21418558", "http://www.ncbi.nlm.nih.gov/pubmed/21284896", "http://www.ncbi.nlm.nih.gov/pubmed/21559780", "http://www.ncbi.nlm.nih.gov/pubmed/22417299", "http://www.ncbi.nlm.nih.gov/pubmed/20842113", "http://www.ncbi.nlm.nih.gov/pubmed/21799879", "http://www.ncbi.nlm.nih.gov/pubmed/22312290", "http://www.ncbi.nlm.nih.gov/pubmed/22303318", "http://www.ncbi.nlm.nih.gov/pubmed/23276969", "http://www.ncbi.nlm.nih.gov/pubmed/23016435", "http://www.ncbi.nlm.nih.gov/pubmed/21971665", "http://www.ncbi.nlm.nih.gov/pubmed/23431261", "http://www.ncbi.nlm.nih.gov/pubmed/23158014", "http://www.ncbi.nlm.nih.gov/pubmed/19521961", "http://www.ncbi.nlm.nih.gov/pubmed/23250910", "http://www.ncbi.nlm.nih.gov/pubmed/23554741", "http://www.ncbi.nlm.nih.gov/pubmed/18927107", "http://www.ncbi.nlm.nih.gov/pubmed/22392644", "http://www.ncbi.nlm.nih.gov/pubmed/21903334", "http://www.ncbi.nlm.nih.gov/pubmed/22666523", "http://www.ncbi.nlm.nih.gov/pubmed/22194833", "http://www.ncbi.nlm.nih.gov/pubmed/22616882", "http://www.ncbi.nlm.nih.gov/pubmed/20716340", "http://www.ncbi.nlm.nih.gov/pubmed/22056881", "http://www.ncbi.nlm.nih.gov/pubmed/23251295", "http://www.ncbi.nlm.nih.gov/pubmed/21811665", "http://www.ncbi.nlm.nih.gov/pubmed/19721809", "http://www.ncbi.nlm.nih.gov/pubmed/21962230", "http://www.ncbi.nlm.nih.gov/pubmed/18442408", "http://www.ncbi.nlm.nih.gov/pubmed/20221895", "http://www.ncbi.nlm.nih.gov/pubmed/22384020", "http://www.ncbi.nlm.nih.gov/pubmed/21102580", "http://www.ncbi.nlm.nih.gov/pubmed/22469780", "http://www.ncbi.nlm.nih.gov/pubmed/21712563", "http://www.ncbi.nlm.nih.gov/pubmed/22938091", "http://www.ncbi.nlm.nih.gov/pubmed/17700064", "http://www.ncbi.nlm.nih.gov/pubmed/21931505", "http://www.ncbi.nlm.nih.gov/pubmed/22666228", "http://www.ncbi.nlm.nih.gov/pubmed/23175432", "http://www.ncbi.nlm.nih.gov/pubmed/23024649", "http://www.ncbi.nlm.nih.gov/pubmed/19712461", "http://www.ncbi.nlm.nih.gov/pubmed/21029445", "http://www.ncbi.nlm.nih.gov/pubmed/21860412", "http://www.ncbi.nlm.nih.gov/pubmed/23391324", "http://www.ncbi.nlm.nih.gov/pubmed/16854228", "http://www.ncbi.nlm.nih.gov/pubmed/23407615", "http://www.ncbi.nlm.nih.gov/pubmed/21461395", "http://www.ncbi.nlm.nih.gov/pubmed/18036240", "http://www.ncbi.nlm.nih.gov/pubmed/22126155", "http://www.ncbi.nlm.nih.gov/pubmed/23125218", "http://www.ncbi.nlm.nih.gov/pubmed/22408395", "http://www.ncbi.nlm.nih.gov/pubmed/20925959", "http://www.ncbi.nlm.nih.gov/pubmed/22548175", "http://www.ncbi.nlm.nih.gov/pubmed/23209884", "http://www.ncbi.nlm.nih.gov/pubmed/19638982", "http://www.ncbi.nlm.nih.gov/pubmed/22968430" ], "ideal_answer": [ "MicroRNAs (miRNAs) are endogenous non-protein coding single-stranded RNAs (19\u201325 nucleotides in length) generated from cleavage of larger non-coding RNAs by the ribonuclease III enzyme Dicer. They become part of the RNA-induced silencing complex and negatively regulate gene expression by binding to homologous 3'-UTR region of target protein-coding mRNAs as an imperfect match, causing translational repression or degradation. Approximately one-third of the protein-coding genes are susceptible to miRNA regulation. Accumulating evidence indicates that deregulated miRNA expression is associated with the onset and progression of a number of human cancers. Therefore, cancer-associated miRNAs (CA-miRNAs) could regulate target genes by acting either as \"oncogenes\" or \"tumor suppressor miRNA (TS-miRNAs)\". In line with this, numerous cancers (e.g. breast, lung, oesophageal, prostate, pancreatic, gastric and colon cancer) have been classified based on their unique miRNA expression profile." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "summary", "id": "51718fbc8ed59a060a000010", "snippets": [ { "offsetInBeginSection": 239, "offsetInEndSection": 537, "text": "MicroRNAs are a class of small non-coding RNAs that negatively regulate gene expression by interacting with the 3'UTR of protein-coding mRNA. MicroRNAs are implicated in nearly all major biological and cellular events, and recent findings further link microRNA deregulation to human carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23276969", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "MiR-657 promotes tumorigenesis in hepatocellular carcinoma by targeting transducin-like enhancer protein 1 through NF-\u03baB pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175432", "endSection": "title" }, { "offsetInBeginSection": 195, "offsetInEndSection": 312, "text": "MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in diverse biological functions and carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23125218", "endSection": "sections.0" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1063, "text": "Moreover, we demonstrated that miR-106b downregulates APC expression by directly targeting the 3'-untranslated region of APC messenger RNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23087084", "endSection": "sections.0" }, { "offsetInBeginSection": 287, "offsetInEndSection": 657, "text": "Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064433", "endSection": "sections.0" }, { "offsetInBeginSection": 41, "offsetInEndSection": 602, "text": "MicroRNAs, known as small noncoding MiRNAs, 19 to 24 nt in length, are important gene regulators and recognized as key players in carcinogenesis. The mechanism lies in that the MiRNAs can conjugate with their targeted mRNA and then lead to the targeted mRNA degradation or repress their translation. Bioinformatic analysis indicates that each MiRNA can regulate hundreds of gene targets and could serve functionally as \"oncogenes\" or \"tumor suppressor genes\", and therefore regulate multiple cellular processes relevant to carcinogenesis and cancer progression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23016435", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "microRNAs (miRs) are endogenous small non-coding RNAs that are aberrantly expressed in various carcinomas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21971665", "endSection": "sections.0" }, { "offsetInBeginSection": 89, "offsetInEndSection": 253, "text": "While deregulated miRNA expression levels have been detected in many tumors, whether miRNA functional impairment is also involved in carcinogenesis remains unknown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22898998", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "In the last years, microRNAs (miRNA) have emerged as new molecular players involved in carcinogenesis. Deregulation of miRNAs expression has been shown in different human cancer but the molecular mechanism underlying the alteration of miRNA expression is unknown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19521961", "endSection": "sections.0" }, { "offsetInBeginSection": 269, "offsetInEndSection": 730, "text": "These are microRNAs (miRNAs), a class of noncoding RNAs, 20-23 nucleotides in length, that can up or downregulate gene expression of downstream gene targets (including transcription factors, oncogenes, and tumour suppressor genes) at the post-transcriptional level. Some members of this new class of genes seem to have the potential to act simultaneously either as oncogenes or as tumour suppressor genes depending on the molecular microenvironment of the cell.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903334", "endSection": "sections.0" }, { "offsetInBeginSection": 144, "offsetInEndSection": 240, "text": "MicroRNAs can also be affected by chromosomal alterations and thus contribute to carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22469780", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Regulation of hepatocarcinogenesis by microRNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23276969", "endSection": "title" }, { "offsetInBeginSection": 381, "offsetInEndSection": 537, "text": "MicroRNAs are implicated in nearly all major biological and cellular events, and recent findings further link microRNA deregulation to human carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23276969", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "miR-106b downregulates adenomatous polyposis coli and promotes cell proliferation in human hepatocellular carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23087084", "endSection": "title" }, { "offsetInBeginSection": 453, "offsetInEndSection": 657, "text": "However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064433", "endSection": "sections.0" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1681, "text": "Combined with previous cancer studies, the analysis of the relevance between functions of CA-miRNAs and cancer-related pathways exploring different internal carcinogenesis stimuli also revealed the potential of the top five pathways to regulate core carcinogenesis processes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064433", "endSection": "sections.0" }, { "offsetInBeginSection": 41, "offsetInEndSection": 186, "text": "MicroRNAs, known as small noncoding MiRNAs, 19 to 24 nt in length, are important gene regulators and recognized as key players in carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23016435", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392644", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392644", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056881", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056881", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175432", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "UNLABELLED: Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392644", "endSection": "sections.0" }, { "offsetInBeginSection": 103, "offsetInEndSection": 263, "text": "Deregulation of miRNAs expression has been shown in different human cancer but the molecular mechanism underlying the alteration of miRNA expression is unknown.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19521961", "endSection": "sections.0" } ] }, { "body": "Which type of GTPases is required for amino acid-dependent activation of mTORC1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24698685", "http://www.ncbi.nlm.nih.gov/pubmed/25263562", "http://www.ncbi.nlm.nih.gov/pubmed/24081491", "http://www.ncbi.nlm.nih.gov/pubmed/22424946", "http://www.ncbi.nlm.nih.gov/pubmed/24337580", "http://www.ncbi.nlm.nih.gov/pubmed/24095279", "http://www.ncbi.nlm.nih.gov/pubmed/25567907", "http://www.ncbi.nlm.nih.gov/pubmed/25567906", "http://www.ncbi.nlm.nih.gov/pubmed/23863162", "http://www.ncbi.nlm.nih.gov/pubmed/25936802", "http://www.ncbi.nlm.nih.gov/pubmed/21981924" ], "ideal_answer": [ "Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome", "Amino acids act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation." ], "exact_answer": [ "Heterodimeric Rag GTPases" ], "type": "factoid", "id": "56cdf3e55795f9a73e00003c", "snippets": [ { "offsetInBeginSection": 108, "offsetInEndSection": 204, "text": "Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25936802", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 344, "text": "Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567906", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 661, "text": "mTORC1 promotes growth in response to the availability of nutrients, such as amino acids, which drive mTORC1 to the lysosomal surface, its site of activation. How amino acid levels are communicated to mTORC1 is only recently coming to light by the discovery of a lysosome-based signaling system composed of Rags (Ras-related GTPases) and Ragulator v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24698685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a major regulator of cell growth that responds to numerous environmental cues. A key input is amino acids, which act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263562", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 635, "text": "The heterodimeric Rag GTPases localize mTORC1 to lysosomes by their amino-acid-dependent interaction with the lysosomal Ragulator complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863162", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1274, "text": "These new findings define the lysosome as a site of action for FLCN and indicate a critical role for FLCN in the amino acid-dependent activation of mTOR via its direct interaction with the RagA/B GTPases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24081491", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1061, "text": "We show that LRS directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein (GAP) for Rag GTPase to activate mTORC1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22424946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Activation of mammalian target of rapamycin complex 1 (mTORC1) by amino acids is mediated in part by the Rag GTPases, which bind the raptor subunit of mTORC1 in an amino acid-stimulated manner and promote mTORC1 interaction with Rheb-GTP, the immediate activator", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24337580", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 271, "text": "The Rag GTPases interact with mTORC1 and signal amino acid sufficiency by promoting the translocation of mTORC1 to the lysosomal surface, its site of activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24095279", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 364, "text": "Amino acids stimulate mTORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuolar H(+)-adenosine triphosphatase (v-ATPase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567907", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 206, "text": "Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25936802", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 346, "text": "Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567906", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1075, "text": "These new findings define the lysosome as a site of action for FLCN and indicate a critical role for FLCN in the amino acid-dependent activation of mTOR via its direct interaction with the RagA/B GTPases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24081491", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 801, "text": "Interestingly, p62 colocalizes with Rags at the lysosomal compartment and is required for the interaction of mTOR with Rag GTPases in vivo and for translocation of the mTORC1 complex to the lysosome, a crucial step for mTOR activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21981924", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 595, "text": "Our results indicate that FLCN is specifically required for the amino acid-stimulated recruitment of mTORC1 to lysosomes by Rag GTPases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24081491", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 852, "text": "Mutation of LRS amino acid residues important for leucine binding renders the mTORC1 pathway insensitive to intracellular levels of amino acids. We show that LRS directly binds to Rag GTPase, the mediator of amino acid signaling to mTORC1, in an amino acid-dependent manner and functions as a GTPase-activating protein (GAP) for Rag GTPase to activate mTORC1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22424946", "endSection": "abstract" } ] }, { "body": "In which genomic regions are Alu enriched?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2716062", "http://www.ncbi.nlm.nih.gov/pubmed/12777511", "http://www.ncbi.nlm.nih.gov/pubmed/6165649", "http://www.ncbi.nlm.nih.gov/pubmed/23420552", "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "http://www.ncbi.nlm.nih.gov/pubmed/11884141" ], "ideal_answer": [ "There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome. Alu elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins.\nThis bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions.", "There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome." ], "exact_answer": [ [ "genes which are involved in metabolism, transport, and signaling processes" ], [ "gene conversion-prone regions" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020087" ], "type": "list", "id": "570921e4cf1c325851000017", "snippets": [ { "offsetInBeginSection": 121, "offsetInEndSection": 317, "text": "There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 664, "text": "These elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 865, "text": "This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1078, "text": "The relative proportions of Alu subfamilies (Alu J, Alu S, and Alu Y) are not significantly different in genes with high Alu density belonging to the functional categories of transport, metabolism, and signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1332, "text": "We suggest that Alu elements might be involved in regulatory mechanisms and are therefore differentially selected in primate genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 666, "text": "Sequence analysis demonstrated these \"young\" Alu insertions represented gene conversion events of pre-existing ancient Alu elements or independent parallel insertions of older Alu elements in the same genomic region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11884141", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1171, "text": "This study suggests that the majority of Alu insertions in primate genomes are the products of unique evolutionary events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11884141", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 745, "text": "Our screening of the Alu insertion loci also resulted in the recovery of several \"young\" Alu elements that resided at orthologous positions in nonhuman primate genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777511", "endSection": "abstract" } ] }, { "body": "What is the synonym of the lubag disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12465067", "http://www.ncbi.nlm.nih.gov/pubmed/8041372", "http://www.ncbi.nlm.nih.gov/pubmed/1672807", "http://www.ncbi.nlm.nih.gov/pubmed/21047175", "http://www.ncbi.nlm.nih.gov/pubmed/23614923", "http://www.ncbi.nlm.nih.gov/pubmed/18609312", "http://www.ncbi.nlm.nih.gov/pubmed/17579361", "http://www.ncbi.nlm.nih.gov/pubmed/12471465", "http://www.ncbi.nlm.nih.gov/pubmed/15390042", "http://www.ncbi.nlm.nih.gov/pubmed/25004170", "http://www.ncbi.nlm.nih.gov/pubmed/8351010", "http://www.ncbi.nlm.nih.gov/pubmed/8338342", "http://www.ncbi.nlm.nih.gov/pubmed/15465396", "http://www.ncbi.nlm.nih.gov/pubmed/20694531", "http://www.ncbi.nlm.nih.gov/pubmed/16242937", "http://www.ncbi.nlm.nih.gov/pubmed/15596620", "http://www.ncbi.nlm.nih.gov/pubmed/8341310", "http://www.ncbi.nlm.nih.gov/pubmed/23184149" ], "ideal_answer": [ "Lubag disease is also known as X-linked dystonia-parkinsonism (XDP). This disease is characterized by dystonia and parkinsonism, and afflicts Filipino men, and rarely, women originating principally from the Panay Island." ], "exact_answer": [ "X-linked dystonia-parkinsonism" ], "type": "factoid", "id": "54df695b1388e8454a000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "IMPORTANCE: Despite recessive inheritance, X-linked dystonia-parkinsonism (Lubag disease) has also been described in women presenting with a late-onset isolated parkinsonian syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25004170", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Anesthesia for deep brain stimulation in a patient with X-linked dystonia-parkinsonism/Lubag disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23614923", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23614923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184149", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "X-chromosomal dystonia parkinsonism syndrome (XDP, 'lubag') is associated with sequence changes within the TAF1/DYT3 multiple transcript system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "The unique phenomenology of sex-linked dystonia parkinsonism (XDP, DYT3, \"Lubag\").", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047175", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Sex-linked dystonia parkinsonism (XDP, DYT3, \"Lubag\") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Islands in 1975. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047175", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 992, "text": "We cover dopa-responsive dystonia, Wilson's disease, Parkin-, PINK1-, and DJ-1-associated parkinsonism (PARK2, 6, and 7), x-linked dystonia-parkinsonism/Lubag (DYT3), rapid-onset dystonia-parkinsonism (DYT12) and DYT16 dystonia, the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) including pantothenate kinase (PANK2)- and PLA2G6 (PARK14)-associated neurodegeneration, neuroferritinopathy, Kufor-Rakeb disease (PARK9) and the recently described SENDA syndrome; FBXO7-associated neurodegeneration (PARK15), autosomal-recessive spastic paraplegia with a thin corpus callosum (SPG11), and dystonia parkinsonism due to mutations in the SLC6A3 gene encoding the dopamine transporter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20694531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Neuropsychological profile of a Filipino gentleman with X-linked dystonia-parkinsonism: a case report of Lubag disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18609312", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "X-Linked Dystonia-Parkinsonism (XDP or \"Lubag\") is a progressive neurodegenerative disorder unique to the Island of Panay in the Philippines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18609312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "First case of X-linked dystonia-parkinsonism (\"Lubag\") to demonstrate a response to bilateral pallidal stimulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17579361", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "\"Lubag\" or X-linked dystonia-parkinsonism (XDP) is a genetic syndrome afflicting Filipino men.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17579361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "First case report of X linked dystonia parkinsonism (XDP) or 'lubag' in Australia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16242937", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "PURPOSE: To present the first genetically supported case of X linked dystonia parkinsonism (XDP) or 'lubag' reported in an Australian hospital. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16242937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Phenotypic and molecular analyses of X-linked dystonia-parkinsonism (\"lubag\") in women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15596620", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "BACKGROUND: X-linked dystonia-parkinsonism (XDP) or \"lubag\" is an X-linked recessive disorder that afflicts Filipino men, and rarely, women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15596620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Smell testing is abnormal in 'lubag' or X-linked dystonia-parkinsonism: a pilot study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15465396", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "We administered a culturally corrected University of Pennsylvania Smell Identification Test (ccUPSIT) consisting of 25 odor items to 20 patients with 'Lubag' or X-linked dystonia-parkinsonism and 20 control subjects matched by sex, age, educational background, smoking history, and geographical origin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15465396", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 458, "text": "Three affected siblings were found to share an identical haplotype at the X-linked dystonia-parkinsonism locus (XDP; Lubag; OMIM*314250).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15390042", "endSection": "abstract" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1216, "text": "These neuropathological findings differed from those of Parkinson's disease or juvenile parkinsonism, but mimic to those of X-linked dystonia parkinsonism (Lubag).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12471465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Phenomenology of \"Lubag\" or X-linked dystonia-parkinsonism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12465067", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "X-linked dystonia-parkinsonism (XDP), or Lubag syndrome, is known to cause progressive dystonia, with or without parkinsonism, among Filipino male adults with maternal roots from the Philippine island of Panay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12465067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Adductor laryngeal breathing dystonia in a patient with lubag (X-linked dystonia-Parkinsonism syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8041372", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "We report a patient with Lubag (X-linked dystonia-parkinsonism) who presented with severe respiratory stridor from adductor laryngeal breathing dystonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8041372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Phenotypic expression of X-linked dystonia-parkinsonism (lubag) in two women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8351010", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Lubag (X-linked dystonia-parkinsonism) has been considered a sex-linked recessive trait and has been mapped to the pericentromeric region of the X chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8351010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Regional and global metabolic rates for glucose (rCMRGlc and GMR) were estimated using [18F]fluorodeoxyglucose and positron emission tomography in 3 patients with Filipino X-linked dystonia-parkinsonism (lubag). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8338342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Neuropathology of lubag (x-linked dystonia parkinsonism).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8341310", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Lubag is an x-linked recessive dystonia parkinsonism that affects Filipino men originating principally from the Panay Island.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8341310", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Genetic mapping of \"Lubag\" (X-linked dystonia-parkinsonism) in a Filipino kindred to the pericentromeric region of the X chromosome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1672807", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "\"Lubag\" is an X-linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, principally from the island of Panay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1672807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "X-Linked Dystonia-Parkinsonism (XDP or \"Lubag\") is a progressive neurodegenerative disorder unique to the Island of Panay in the Philippines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18609312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23614923", "endSection": "abstract" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1215, "text": "These neuropathological findings differed from those of Parkinson's disease or juvenile parkinsonism, but mimic to those of X-linked dystonia parkinsonism (Lubag)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12471465", "endSection": "abstract" } ] }, { "body": "Dracorhodin perchlorate was tested for treatment of which cancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "http://www.ncbi.nlm.nih.gov/pubmed/15215653", "http://www.ncbi.nlm.nih.gov/pubmed/16864444", "http://www.ncbi.nlm.nih.gov/pubmed/22711363", "http://www.ncbi.nlm.nih.gov/pubmed/15684474", "http://www.ncbi.nlm.nih.gov/pubmed/21505988" ], "ideal_answer": [ "Dracorhodin perchlorate induce apoptosis in prostate cancer, gastric tumor, melanoma and premyelocytic leukemia." ], "exact_answer": [ [ "prostate cancer" ], [ "gastric tumor" ], [ "melanoma" ], [ "premyelocytic leukemia" ] ], "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4016161", "http://www.biosemantics.org/jochem#4016161" ], "type": "list", "id": "56bcdf1ad36b5da378000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Dracorhodin perchlorate induced human breast cancer MCF-7 apoptosis through mitochondrial pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "endSection": "title" }, { "offsetInBeginSection": 123, "offsetInEndSection": 317, "text": "It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "endSection": "abstract" }, { "offsetInBeginSection": 1550, "offsetInEndSection": 1675, "text": "CONCLUSION: Therefore DP was a candidate for anti-breast cancer, DP induced apoptosis of MCF-7 through mitochondrial pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Dracorhodin perchlorate has been recently shown to induce apoptotic cell death in cancer cells. However, the molecular mechanisms underlying these effects are unknown in human gastric tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22711363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Dracorhodin perchlorate suppresses proliferation and induces apoptosis in human prostate cancer cell line PC-3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Dracorhodin perchlorate, an anthocyanin red pigment, induces human premyelocytic leukemia HL-60 cell death through apoptotic pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16864444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Dracorhodin perchlorate, an anthocyanin red pigment, induces human melanoma A375-S2 cell death through the apoptotic pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15684474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Dracorhodin perchlorate inhibited proliferation of several tumor cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 318, "text": "It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": " Dracorhodin perchlorate (DP) was a synthetic analogue of the antimicrobial anthocyanin red pigment dracorhodin. It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": " The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 \u03bcmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 401, "text": "It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated. This study would investigate whether DP was a candidate chemical of anti-human breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Dracorhodin perchlorate (DP) was a synthetic analogue of the antimicrobial anthocyanin red pigment dracorhodin. It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 \u03bcmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505988", "endSection": "abstract" } ] }, { "body": "What is the role of venous angioplasty in multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22687168", "http://www.ncbi.nlm.nih.gov/pubmed/21059535", "http://www.ncbi.nlm.nih.gov/pubmed/23563645", "http://www.ncbi.nlm.nih.gov/pubmed/21803799", "http://www.ncbi.nlm.nih.gov/pubmed/21487978", "http://www.ncbi.nlm.nih.gov/pubmed/21856578", "http://www.ncbi.nlm.nih.gov/pubmed/22496109", "http://www.ncbi.nlm.nih.gov/pubmed/22088659", "http://www.ncbi.nlm.nih.gov/pubmed/22311713", "http://www.ncbi.nlm.nih.gov/pubmed/23691321", "http://www.ncbi.nlm.nih.gov/pubmed/21679067", "http://www.ncbi.nlm.nih.gov/pubmed/20351673", "http://www.ncbi.nlm.nih.gov/pubmed/22577160", "http://www.ncbi.nlm.nih.gov/pubmed/23202144", "http://www.ncbi.nlm.nih.gov/pubmed/20351675", "http://www.ncbi.nlm.nih.gov/pubmed/22640501", "http://www.ncbi.nlm.nih.gov/pubmed/23701076", "http://www.ncbi.nlm.nih.gov/pubmed/23493652", "http://www.ncbi.nlm.nih.gov/pubmed/23660636", "http://www.ncbi.nlm.nih.gov/pubmed/23523158", "http://www.ncbi.nlm.nih.gov/pubmed/21839654", "http://www.ncbi.nlm.nih.gov/pubmed/23809937", "http://www.ncbi.nlm.nih.gov/pubmed/23948669", "http://www.ncbi.nlm.nih.gov/pubmed/23235683", "http://www.ncbi.nlm.nih.gov/pubmed/22648477", "http://www.ncbi.nlm.nih.gov/pubmed/21876515", "http://www.ncbi.nlm.nih.gov/pubmed/22569567", "http://www.ncbi.nlm.nih.gov/pubmed/23034121", "http://www.ncbi.nlm.nih.gov/pubmed/22987234", "http://www.ncbi.nlm.nih.gov/pubmed/20373339", "http://www.ncbi.nlm.nih.gov/pubmed/23249660", "http://www.ncbi.nlm.nih.gov/pubmed/22951366", "http://www.ncbi.nlm.nih.gov/pubmed/24255092", "http://www.ncbi.nlm.nih.gov/pubmed/23419569", "http://www.ncbi.nlm.nih.gov/pubmed/21106999", "http://www.ncbi.nlm.nih.gov/pubmed/23953830", "http://www.ncbi.nlm.nih.gov/pubmed/24975855", "http://www.ncbi.nlm.nih.gov/pubmed/23781006", "http://www.ncbi.nlm.nih.gov/pubmed/19958985", "http://www.ncbi.nlm.nih.gov/pubmed/23402260", "http://www.ncbi.nlm.nih.gov/pubmed/21107001", "http://www.ncbi.nlm.nih.gov/pubmed/21808631", "http://www.ncbi.nlm.nih.gov/pubmed/22155803", "http://www.ncbi.nlm.nih.gov/pubmed/23301864", "http://www.ncbi.nlm.nih.gov/pubmed/23443168" ], "ideal_answer": [ "Chronic cerebrospinal venous insufficiency (CCSVI) may be an important factor in the pathogenesis of multiple sclerosis (MS). The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain, thereby alleviating some of the symptoms of MS. There have been reports to suggest that venous angioplasty in MS patients is a feasible and safe procedure and is associated with improved disease symptom severity, quality of life, and corrects blood pressure deviation, improves CSF dynamics. Open venous reconstruction of the internal jugular vein has also been tried with good results.\nHowever, some authors have failed to document beneficial value of venous angioplasty in MS patients and systematic review has suggested that there is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2377" ], "type": "summary", "id": "550331abe9bde69634000037", "snippets": [ { "offsetInBeginSection": 1850, "offsetInEndSection": 1977, "text": "Balloon angioplasty corrects blood pressure deviation in multiple sclerosis patients undergoing internal jugular vein dilation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "PURPOSE: To investigate prevalence of extracranial abnormalities in azygos and internal jugular (IJ) veins using conventional venography and intravascular ultrasound (IVUS) in patients with multiple sclerosis (MS) being evaluated for chronic cerebrospinal venous insufficiency, a condition of vascular hemodynamic dysfunction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23953830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Feasibility and safety of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23948669", "endSection": "title" }, { "offsetInBeginSection": 2026, "offsetInEndSection": 2099, "text": "CONCLUSIONS: Endovascular treatment for CCSVI appears feasible and safe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23948669", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 433, "text": "This report presents the case of a 45-year-old man with known MS and suspected CCSVI who had undergone previous internal jugular angioplasty and stenting. The patient reported dramatic improvement of symptoms after intervention. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23809937", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 851, "text": "Open venous reconstruction of the internal jugular vein was performed with a spiral graft from the saphenous vein. The patient's symptoms improved for several weeks until the venous reconstruction occluded. This case is the first reported open venous reconstruction for suspected CCSVI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23809937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency in people with multiple sclerosis: a summary of a Cochrane systematic review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781006", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "BACKGROUND: It has been recently hypothesised that chronic cerebrospinal venous insufficiency (CCSVI) may be an important factor in the pathogenesis of multiple sclerosis (MS). The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain, thereby alleviating some of the symptoms of MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781006", "endSection": "abstract" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1262, "text": "CONCLUSIONS: There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781006", "endSection": "abstract" }, { "offsetInBeginSection": 1813, "offsetInEndSection": 2019, "text": "CONCLUSION: The results of the current study suggest that endovascular evaluation and management of chronic cerebrospinal venous insufficiency is safe, with low morbidity and no procedure-related mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23701076", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 945, "text": "There are clinical trials ongoing or planned to treat chronic cerebrospinal venous insufficiency (CCSVI) through angioplasty. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23691321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Percutaneous transluminal angioplasty for chronic cerebrospinal venous insufficiency in multiple sclerosis: dichotomy between subjective and objective outcome scores.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23660636", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Some multiple sclerosis (MS) patients reported an improvement after percutaneous transluminal angioplasty (PTA) for chronic cerebrospinal venous insufficiency (CCSVI), despite the lack of correspondence with objective outcome scores. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23660636", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1300, "text": " Spontaneously performed approach to CCSVI does not improve clinical and MRI parameters, despite frequent subjective perception of quality of life improvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23660636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Percutaneous angioplasty of internal jugular and azygous veins in patients with chronic cerebrospinal venous insufficiency and multiple sclerosis: early and mid-term results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23563645", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Purpose: To assess the safety of endovascular treatment of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23563645", "endSection": "abstract" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1831, "text": ".Conclusion: Endovascular treatment of the IJV and azygous veins in patients with CCSVI and MS is a safe procedure with no post-procedural complications followed by significant improvement of IJV flow haemodynamic parameters and decrease in the EDSS score. Whether CCSVI percutaneous treatment might affect clinical improvement in patients suffering from MS is yet to be seen after completion of major multicentric clinical trials, still it seems like that this procedure is not negligible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23563645", "endSection": "abstract" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1810, "text": " CONCLUSIONS: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "BACKGROUND: It has been postulated that Multiple sclerosis (MS) stems from a narrowing in the veins that drain blood from the brain, known medically as chronic cerebrospinal venous insufficiency, or CCSVI. It has been proposed that balloon angioplasty should alleviate the symptoms of MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23493652", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 688, "text": " The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of 'CCSVI' could alleviate MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23443168", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 1022, "text": " The data obtained here do generally not support the 'CCSVI' concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23443168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "RATIONALE: It is estimated that some hundreds of Canadian patients with multiple sclerosis (MS) have journeyed abroad to avail themselves of 'liberation therapy' (venoplasty) following the initial report by Zamboni et al in 2009. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419569", "endSection": "abstract" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1400, "text": "CONCLUSION: No objective improvement was found at one year in thirty MS subjects who had undergone venoplasty, although many reported a degree of subjective benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419569", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 274, "text": "Zamboni et al. reported significant improvement in neurological outcomes in MS patients who underwent percutaneous transluminal angioplasty (PTA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23301864", "endSection": "abstract" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1733, "text": "CONCLUSION: The study revealed that PTA in relapsing remitting MS patients was not associated with any neurological improvement. However, there was an increase in disease activity irrespective of the adherence to DMTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23301864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Serious complication of percutaneous angioplasty with stent implantation in so called \"chronic cerebrospinal venous insufficiency\" in multiple sclerosis patient.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23249660", "endSection": "title" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1082, "text": "We strongly ask for restriction of PTA procedure in so called CCSVI, which concept was not proven to be relevant to MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23249660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23235683", "endSection": "title" }, { "offsetInBeginSection": 682, "offsetInEndSection": 903, "text": "The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23235683", "endSection": "abstract" }, { "offsetInBeginSection": 2031, "offsetInEndSection": 2222, "text": "AUTHORS' CONCLUSIONS: There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23235683", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 796, "text": "Significant improvement of clinical disability in relapsing-remitting patients was (P < 0.001) achieved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23202144", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 647, "text": "Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034121", "endSection": "abstract" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1422, "text": "CONCLUSION: In the case presented, PTA of the IJV confluence resulted in haemodynamic improvement despite the presence of IJV external compression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987234", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1685, "text": "CONCLUSIONS: Endovascular treatment of CCSVI in patients with MS appears to be a safe procedure resulting in significant clinical improvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22951366", "endSection": "abstract" }, { "offsetInBeginSection": 1728, "offsetInEndSection": 1905, "text": "Endovascular treatment of concurrent CCSVI seems to be safe and repeatable and may reduce annual relapse rates and cumulative disability in patients with relapsing-remitting MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22687168", "endSection": "abstract" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1495, "text": "Therefore, any potentially harmful interventional treatment such as transluminal angioplasty and/or stenting should be strongly discouraged.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22648477", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1173, "text": "The work of Dr. Zamboni, et al, who reported that treating the venous stenoses causing CCSVI with angioplasty resulting in significant improvement in the symptoms and quality of life of patients with MS (2) has led to further interest in this theory and potential treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22640501", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 493, "text": "Regardless of this continued uncertainty surrounding the safety and efficacy of this therapy, MS patients from Canada, and other jurisdictions, are traveling abroad to receive central venous angioplasty and, unfortunately, some also receive venous stents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577160", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1150, "text": "Finally, no proven (i.e., based on strict scientific methodology and on the rules of evidence-based medicine) therapeutic effect of the \"liberation\" procedure (unblocking the extracranial venous obstruction using angioplasty) has been shown up to date.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22569567", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 957, "text": "The angiographic and hemodynamic improvement was associated with improvement in symptomatology, most particularly in cognitive and constitutional symptoms that may be related to cerebrovenous flow. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496109", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1287, "text": " In conclusion, in this series, endovascular intervention to correct venous stenosis associated with multiple sclerosis was associated with improvement in symptoms possibly related to disturbed venous hemodynamics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496109", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1385, "text": "Some investigators have proceeded to unblinded nonrandomized angioplasty and stenting procedures in patients with CCSVI, with anecdotal reports of symptom improvement. Because of conflicting data on the presence of CCSVI and the absence of controlled trials of CCSVI intervention, the current standard of clinical care is neither to evaluate multiple sclerosis (MS) patients for CCSVI anomalies, nor to intervene with procedures to alter such anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22311713", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 640, "text": "Endovascular treatment (percutaneous transluminal angioplasty (PTA) with or without stenting) of CCSVI was reported to be feasible with a minor complication rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155803", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1363, "text": "PTA seems to be an effective treatment for patients with CCVI and multiple sclerosis, However, randomized studies are warranted to establish the efficacy of this new treatment for MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155803", "endSection": "abstract" }, { "offsetInBeginSection": 1577, "offsetInEndSection": 1687, "text": "CONCLUSIONS: Endovascular treatment of CCSVI is a safe procedure; there is a 1.6% risk of major complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088659", "endSection": "abstract" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1837, "text": "CONCLUSIONS: The endovascular treatment in patients with MS and concomitant CCSVI did not have an influence on the patient's neurological condition; however, in the mid-term follow-up, an improvement in some quality-of-life parameters was observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876515", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 678, "text": "Although there is no methodologically rigorous evidence to support this hypothesis presently, a considerable number of MS patients have undergone endovascular CCSVI procedures. Such procedures include angioplasty or stent placement in jugular and azygous veins. The safety and efficacy of these procedures is unknown, but not without risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856578", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1352, "text": "CONCLUSIONS: As the debate about CCSVI and its relationship to MS continues, the complications and risks associated with venous stenting and angioplasty in jugular and azygous veins are becoming clearer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856578", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1358, "text": "CONCLUSIONS: This study further confirms the safety of PTA treatment in patients with CCSVI associated with MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839654", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 581, "text": "This review aims to describe the proposed association between CCSVI and MS, summarize the current data, and discuss the role of endovascular therapy and the need for rigorous randomized clinical trials to evaluate this association and treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21808631", "endSection": "abstract" }, { "offsetInBeginSection": 1451, "offsetInEndSection": 1544, "text": "CONCLUSION: Endovascular therapy appears to be a safe and reliable method for treating CCSVI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679067", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 999, "text": "In particular, the potential shift in treatment concepts possibly leading to an interventional treatment approach including balloon angioplasty and venous stent placement is currently being debated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21487978", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1688, "text": "In conclusion, the present conclusive data confuting the theory of CCSVI in MS should lead to reluctance with respect to the interventional treatment of possible venous anomalies in MS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21487978", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 315, "text": "Although balloon angioplasty and stenting seem to be safe procedures, there are currently no data on the treatment of a large group of patients with this vascular pathology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21107001", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1564, "text": "CONCLUSIONS: The procedures appeared to be safe and well tolerated by the patients, regardless of the actual impact of the endovascular treatments for venous pathology on the clinical course of multiple sclerosis, which warrants long-term follow-up.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21107001", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1408, "text": "Two pilot studies demonstrated the safety and feasibility in Day Surgery of the endovascular treatment of CCSVI by means of balloon angioplasty (PTA). It determines a significant reduction of postoperative venous pressure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106999", "endSection": "abstract" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 1625, "text": "However, PTA seems to positively influence clinical and QoL parameters of the associated MS and warrants further randomized control trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106999", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 700, "text": "Furthermore, they have obtained apparent clinical improvement or stabilization by endovascular ballooning of points of obstruction in the great veins in some, at least temporarily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21059535", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 579, "text": "A potential shift in the treatment paradigm of MS involving endovascular balloon angioplasty or venous stent placement has been proposed as well as conducted in small patient series. In some cases, it may have resulted in serious injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20373339", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1264, "text": " At present, invasive and potentially dangerous endovascular procedures as therapy for patients with MS should be discouraged until such studies have been completed, analyzed, and debated in the scientific arena.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20373339", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 1125, "text": "She underwent percutaneous balloon angioplasty of the associated chronic cerebrospinal venous insufficiency (CCSVI), due to membranous obstruction of the proximal azygous vein, with severe stenosis of the left internal jugular vein. Treatment of the associated CCSVI made a parallel improvement in both clinical and neurophysiological parameters, allowing us to avoid high dose steroid therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20351675", "endSection": "abstract" }, { "offsetInBeginSection": 2113, "offsetInEndSection": 2352, "text": "CONCLUSIONS: PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19958985", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 996, "text": "In particular, the potential shift in treatment concepts possibly leading to an interventional treatment approach including balloon angioplasty and venous stent placement is currently being debated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21487978", "endSection": "abstract" } ] }, { "body": "Are the Fanconi anemia genes a part of the same signalling pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23333482", "http://www.ncbi.nlm.nih.gov/pubmed/15611632", "http://www.ncbi.nlm.nih.gov/pubmed/20407210", "http://www.ncbi.nlm.nih.gov/pubmed/11157805", "http://www.ncbi.nlm.nih.gov/pubmed/10088637", "http://www.ncbi.nlm.nih.gov/pubmed/21557222", "http://www.ncbi.nlm.nih.gov/pubmed/17387268" ], "ideal_answer": [ "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA ", "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNAMutations in at least 14 different genes have been shown to cause FA", "Mutations in at least 14 different genes have been shown to cause FA. The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA. ", "The Fanconi anemia genes code for proteins that act in complexes to coordinate the repair of damaged DNA.", "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA. Mutations in at least 14 different genes have been shown to cause FA. " ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13636", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015398", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007165" ], "type": "yesno", "id": "54f42f2764850a5854000005", "snippets": [ { "offsetInBeginSection": 217, "offsetInEndSection": 285, "text": "Mutations in at least 14 different genes have been shown to cause FA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21557222", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 519, "text": "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21557222", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 630, "text": " The current review describes the structure and function of the Fanconi anemia genes and describes the role of the encoded Fanconi anemia proteins in a cellular pathway controlling chromosome stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10088637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Fanconi anemia (FA) is a rare human genetic disease caused by mutations in any one of 13 known genes that encode proteins functioning in one common signaling pathway, the FA pathway, or in unknown genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20407210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in one of fifteen genes known to encode FA pathway components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Fanconi anemia (FA) proteins function in a DNA damage response pathway that appears to be part of the network including breast cancer susceptibility gene products, BRCA1 and BRCA2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15611632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Fanconi anemia (FA) proteins function in a DNA damage response pathway that appears to be part of the network including breast cancer susceptibility gene products, BRCA1 and BRCA2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15611632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Fanconi anemia (FA) is a rare human genetic disease caused by mutations in any one of 13 known genes that encode proteins functioning in one common signaling pathway, the FA pathway, or in unknown genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20407210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The Fanconi anemia (FA) gene family comprises at least 12 genes interacting in a common pathway involved in DNA repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387268", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1396, "text": "These findings show that the newly identified FANCE protein is an integral part of the FA pathway, and support the concept of a functional link between all known proteins encoded by the genes that are mutated in this disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11157805", "endSection": "abstract" } ] }, { "body": "Are there clinical trials using stem cells for the treatment of cardiac disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23746978", "http://www.ncbi.nlm.nih.gov/pubmed/25858066", "http://www.ncbi.nlm.nih.gov/pubmed/25984329", "http://www.ncbi.nlm.nih.gov/pubmed/19804333", "http://www.ncbi.nlm.nih.gov/pubmed/25169179", "http://www.ncbi.nlm.nih.gov/pubmed/23773460", "http://www.ncbi.nlm.nih.gov/pubmed/17198039", "http://www.ncbi.nlm.nih.gov/pubmed/20560035", "http://www.ncbi.nlm.nih.gov/pubmed/20680811", "http://www.ncbi.nlm.nih.gov/pubmed/19907881", "http://www.ncbi.nlm.nih.gov/pubmed/17888423", "http://www.ncbi.nlm.nih.gov/pubmed/14647535", "http://www.ncbi.nlm.nih.gov/pubmed/19022705", "http://www.ncbi.nlm.nih.gov/pubmed/22405796", "http://www.ncbi.nlm.nih.gov/pubmed/15030272", "http://www.ncbi.nlm.nih.gov/pubmed/16969166", "http://www.ncbi.nlm.nih.gov/pubmed/19857353", "http://www.ncbi.nlm.nih.gov/pubmed/25205213", "http://www.ncbi.nlm.nih.gov/pubmed/21749886", "http://www.ncbi.nlm.nih.gov/pubmed/22943934", "http://www.ncbi.nlm.nih.gov/pubmed/19627664", "http://www.ncbi.nlm.nih.gov/pubmed/15692093", "http://www.ncbi.nlm.nih.gov/pubmed/25145464", "http://www.ncbi.nlm.nih.gov/pubmed/18543793", "http://www.ncbi.nlm.nih.gov/pubmed/21526485", "http://www.ncbi.nlm.nih.gov/pubmed/26259288" ], "ideal_answer": [ "Yes, there exists clinical trials for cardiac stem cell based treatment.", "Yes, there are several clinical trials on the use of stem cells for the treatment of cardiac (heart) disease." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039902", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013234", "http://www.disease-ontology.org/api/metadata/DOID:114" ], "type": "yesno", "id": "56f160a52ac5ed1459000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Therapy with mesenchymal stem cells is one of the promising tools to improve outcomes after myocardial infarction. Adipose-derived stem cells (ASCs) are an ideal source of mesenchymal stem cells due to their abundance and ease of preparation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205213", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 866, "text": "Furthermore, several ongoing clinical trials using ASCs are producing promising results for heart diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205213", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 485, "text": "Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1123, "text": " Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 867, "text": "several ongoing clinical trials using ASCs are producing promising results for heart diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25205213", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Clinical application of adult stem cells for therapy for cardiac disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23773460", "endSection": "title" }, { "offsetInBeginSection": 99, "offsetInEndSection": 712, "text": "Stem cell-based therapies have the potential to fundamentally transform the treatment of ischemic cardiac injury and heart failure by achieving what would have been unthinkable only a few years ago-the Holy Grail of myocardial regeneration. Recent therapeutic approaches involve bone marrow (BM)-derived mononuclear cells and their subsets such as mesenchymal stem/stromal cells (MSCs), endothelial progenitor cells as well as adipose tissue-derived MSCs, cardiac tissue-derived stem cells, and cell combinations. Clinical trials employing these cells have demonstrated that cellular therapy is feasible and safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25145464", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 1122, "text": "Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 486, "text": "se of stem and precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25858066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 828, "text": "Small uncontrolled clinical trials have demonstrated cardiac stem cells as a treatment option for cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17198039", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 600, "text": "Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical trials as bone marrow stem cells did not show significant improvement in cardiac function following transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560035", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1329, "text": "Several clinical trials using adult stem cell have shown improvements in cardiac function, however, the mechanism of their action is unclear and widespread tissue regeneration is not evident.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19022705", "endSection": "abstract" }, { "offsetInBeginSection": 1795, "offsetInEndSection": 1933, "text": "As we await results from larger and more prolonged clinical trials, the science of stem cell therapy in cardiac disease keeps progressing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19804333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Stem cell therapy for treatment of cardiac disease has shown therapeutic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16969166", "endSection": "abstract" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1617, "text": "It should be noted that stem cell therapy is not limited to the treatment of ischemic cardiac disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14647535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 431, "text": "This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Cell transplantation to repair or regenerate injured myocardium is a new frontier in the treatment of cardiovascular disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17888423", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 411, "text": "Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19857353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": " Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Stem cell therapy for treatment of cardiac disease has shown therapeutic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16969166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25169179", "endSection": "abstract" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1626, "text": "It should be noted that stem cell therapy is not limited to the treatment of ischemic cardiac disease. Non-ischemic cardiomyopathy, peripheral vascular disease, and aging may be treated by stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14647535", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 794, "text": " Recent clinical trials have achieved favorable initial endpoints with improvements in cardiac function and clinical symptoms following cellular therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25984329", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 716, "text": "we consider how cardiac stem cell biology has led us into clinical trials, and we suggest that achieving true cardiac regeneration in patients may ultimately require resolution of critical controversies in experimental cardiac regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746978", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 707, "text": "Cell-based therapies and tissue engineering provide new promising platforms to develop upcoming therapeutic options. Initial clinical trials were able to generate promising results. A variety of different stem cell types have been used for the clinical application. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23773460", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 401, "text": " Insights gained from clinical trials of adult stem cells, together with fundamental scientific advances in cardiac stem cell and regenerative biology, are beginning to yield potential new targets and strategies for regenerative therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22405796", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 494, "text": "Early animal trials have demonstrated the ability to improve cardiac function by transfer of HSCs into the myocardium, and early human studies have demonstrated the feasibility and safety of this approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749886", "endSection": "abstract" } ] }, { "body": "Is DNA methylation an epigenetic modification of chromatin related to gene expression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25512710", "http://www.ncbi.nlm.nih.gov/pubmed/23604474", "http://www.ncbi.nlm.nih.gov/pubmed/25534027", "http://www.ncbi.nlm.nih.gov/pubmed/22359296", "http://www.ncbi.nlm.nih.gov/pubmed/22078060", "http://www.ncbi.nlm.nih.gov/pubmed/25437055", "http://www.ncbi.nlm.nih.gov/pubmed/25531272", "http://www.ncbi.nlm.nih.gov/pubmed/22922032", "http://www.ncbi.nlm.nih.gov/pubmed/25514241", "http://www.ncbi.nlm.nih.gov/pubmed/22992936" ], "ideal_answer": [ "Epigenetic changes such as DNA methylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006306", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000785" ], "type": "yesno", "id": "54d9f7894b1fd0d33c00000a", "snippets": [ { "offsetInBeginSection": 21, "offsetInEndSection": 164, "text": "DNA methylation is a chemical modification of DNA involved in the regulation of gene expression by controlling the access to the DNA sequence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531272", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 163, "text": "Epigenetic marks such as DNA methylation play important biological roles in gene expression regulation and cellular differentiation during development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "DNA methylation patterns are characterized by highly conserved developmental programs, but allow for divergent gene expression resulting from stochastic epigenetic drift or divergent environments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "DNA methylation plays a critical role in the regulation of gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Epigenetic changes such as DNA methylation and histone methylation and acetylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25512710", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 358, "text": "Dysregulation of epigenetic events can be pathological, leading to cardiovascular disease, neurological disorders, metabolic disorders, and cancer development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25512710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Epigenetic control, which includes DNA methylation and histone modifications, leads to chromatin remodeling and regulated gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23604474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Epigenetic modifications on the DNA sequence (DNA methylation) or on chromatin-associated proteins (i.e., histones) comprise the \"cellular epigenome\"; together these modifications play an important role in the regulation of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22992936", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 426, "text": "Epigenetics is a process involved in gene regulation, mediated via DNA methylation, histone modification, chromatin remodeling, and functional noncoding RNAs, which influences the accessibility of the underlying DNA to transcriptional regulatory factors that activate or repress expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22359296", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 322, "text": "Significant progress has been made in the basic understanding of how various epigenetic changes such as DNA methylation, histone modification, miRNA expression, and higher order chromatin structure affect gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22078060", "endSection": "abstract" } ] }, { "body": "Is Growth factor independence 1b (GFI1B) important for hematopoiesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23308270", "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "http://www.ncbi.nlm.nih.gov/pubmed/14530176", "http://www.ncbi.nlm.nih.gov/pubmed/19773260", "http://www.ncbi.nlm.nih.gov/pubmed/19958752", "http://www.ncbi.nlm.nih.gov/pubmed/12351384", "http://www.ncbi.nlm.nih.gov/pubmed/24800817", "http://www.ncbi.nlm.nih.gov/pubmed/18224412", "http://www.ncbi.nlm.nih.gov/pubmed/20124515", "http://www.ncbi.nlm.nih.gov/pubmed/22668850", "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "http://www.ncbi.nlm.nih.gov/pubmed/21606163", "http://www.ncbi.nlm.nih.gov/pubmed/11825872", "http://www.ncbi.nlm.nih.gov/pubmed/22960038", "http://www.ncbi.nlm.nih.gov/pubmed/21732494", "http://www.ncbi.nlm.nih.gov/pubmed/16397623", "http://www.ncbi.nlm.nih.gov/pubmed/21170035", "http://www.ncbi.nlm.nih.gov/pubmed/22885124", "http://www.ncbi.nlm.nih.gov/pubmed/15507521", "http://www.ncbi.nlm.nih.gov/pubmed/20143233", "http://www.ncbi.nlm.nih.gov/pubmed/16177182", "http://www.ncbi.nlm.nih.gov/pubmed/20861919", "http://www.ncbi.nlm.nih.gov/pubmed/17095621", "http://www.ncbi.nlm.nih.gov/pubmed/20826720", "http://www.ncbi.nlm.nih.gov/pubmed/22399799" ], "ideal_answer": [ "Yes. Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030097", "http://www.uniprot.org/uniprot/GFI1B_MOUSE", "http://www.uniprot.org/uniprot/GFI1B_HUMAN" ], "type": "yesno", "id": "553bd2f0f321868558000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 974, "text": "gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1197, "text": "gfi1b is required for definitive hematopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1140, "text": "LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22668850", "endSection": "title" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1076, "text": " Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22668850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "A short Gfi-1B isoform controls erythroid differentiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22399799", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1162, "text": "Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606163", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 922, "text": "This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21170035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Gfi1 and Gfi1b: key regulators of hematopoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919", "endSection": "title" }, { "offsetInBeginSection": 630, "offsetInEndSection": 851, "text": "we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 312, "text": "Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 509, "text": "We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1677, "text": "To date, we have identified two common integration sites involving genes encoding transcription factors that play a critical role in hematopoiesis (Evi1 and Gfi1b loci)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19958752", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 304, "text": "Transcription factors play essential roles in both normal and malignant hematopoiesis. This is the case for the growth factor independent 1b (GFI1B) transcription factor, which is required for erythroid and megakaryocytic differentiation and over-expressed in leukemic patients and cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1450, "text": "We localized several conserved non-coding elements containing multiple erythroid specific transcription factor binding sites at the GFI1B locus. In GFI1B-expressing cells a subset of these conserved non-coding elements and the promoter adopt a close spatial conformation, localize with open chromatin sites, harbor chromatin modifications associated with gene activation and bind multiple transcription factors and co-repressors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1552, "text": "Our findings indicate that GFI1B regulatory elements behave as activators and repressors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19773260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412", "endSection": "abstract" }, { "offsetInBeginSection": 1760, "offsetInEndSection": 1877, "text": "Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Gfi-1 and Gfi-1b are homologous transcriptional repressors involved in diverse developmental contexts, including hematopoiesis and oncogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17095621", "endSection": "title" }, { "offsetInBeginSection": 546, "offsetInEndSection": 958, "text": "We found highly dynamic expression patterns of Gfi1b in erythroid cells, megakaryocytes, and their progenitor cells (MEPS) where Gfi1 is not detected. Vice versa, Gfi1b could not be found in granulocytes, activated macrophages, or their granulomonocytic precursors (GMPs) or in mature naive or activated lymphocytes where Gfi1 is expressed, suggesting a complementary regulation of both loci during hematopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17095621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Gfi1 and Gfi1b act equivalently in haematopoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16397623", "endSection": "title" }, { "offsetInBeginSection": 668, "offsetInEndSection": 814, "text": "our findings show that an intact SNAG domain is essential for all functions of Gfi1 and that Gfi1b can replace Gfi1 functionally in haematopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16397623", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 35, "text": "Gfi-1 oncoproteins in hematopoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14530176", "endSection": "title" }, { "offsetInBeginSection": 101, "offsetInEndSection": 239, "text": "Recent gene targeting experiments and mutational screening in humans have revealed an essential role for Gfi-1 and Gfi-1B in hematopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14530176", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 747, "text": "Gfi-1B disruption is embryonic lethal due to a block of erythropoiesis. Gfi-1B is required for both erythroid and megakaryocyte development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14530176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12351384", "endSection": "title" }, { "offsetInBeginSection": 62, "offsetInEndSection": 222, "text": " we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12351384", "endSection": "abstract" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1665, "text": "These findings establish Gfi-1B as a novel erythroid regulator and reveal its specific involvement in the regulation of erythroid cell growth through modulating erythroid-specific gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12351384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872", "endSection": "title" }, { "offsetInBeginSection": 112, "offsetInEndSection": 237, "text": "we establish that Gfi-1b is required for the development of two related blood lineages, erythroid and megakaryocytic, in mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 475, "text": "Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 714, "text": "Gfi-1b is an essential transcriptional regulator of erythroid and megakaryocyte development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11825872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Growth factor independence 1b (GFI1B) is a DNA binding repressor of transcription with vital functions in hematopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24800817", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1191, "text": "Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17095621", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Gfi1 and Gfi1b: key regulators of hematopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20861919", "endSection": "title" }, { "offsetInBeginSection": 713, "offsetInEndSection": 826, "text": "We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 312, "text": "Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24800817", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20143233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Gfi1b (growth factor independence 1b) is a zinc finger transcription factor essential for development of the erythroid and megakaryocytic lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23308270", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 1072, "text": "In fact, we demonstrate that VPA treatment is able to induce the expression of growth factor-independent protein 1B (GFI1B) and of mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), which are crucial regulators of erythrocyte and megakaryocyte differentiation, and that the up-regulation of these genes is mediated by the histone hyperacetylation at their promoter sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22885124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16177182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Evidence that growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20826720", "endSection": "title" }, { "offsetInBeginSection": 263, "offsetInEndSection": 455, "text": "We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20826720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20143233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960038", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16177182", "endSection": "abstract" }, { "offsetInBeginSection": 1760, "offsetInEndSection": 1878, "text": "Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18224412", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 454, "text": "We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20826720", "endSection": "abstract" } ] }, { "body": "Has Revlimid been approved by the US Food and Drug Administration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25188481", "http://www.ncbi.nlm.nih.gov/pubmed/17996589", "http://www.ncbi.nlm.nih.gov/pubmed/25188483", "http://www.ncbi.nlm.nih.gov/pubmed/23545923", "http://www.ncbi.nlm.nih.gov/pubmed/17076650", "http://www.ncbi.nlm.nih.gov/pubmed/17076653", "http://www.ncbi.nlm.nih.gov/pubmed/20425391", "http://www.ncbi.nlm.nih.gov/pubmed/17242661", "http://www.ncbi.nlm.nih.gov/pubmed/18922829", "http://www.ncbi.nlm.nih.gov/pubmed/22650376", "http://www.ncbi.nlm.nih.gov/pubmed/17020458", "http://www.ncbi.nlm.nih.gov/pubmed/20359632" ], "ideal_answer": [ "Yes, Revlimid has been approved by the US Food and Drug Administration for treatment of multiple myeloma." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014486" ], "type": "yesno", "id": "56ed0ba22ac5ed1459000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 461, "text": "In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25188483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25188481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25188481", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 941, "text": "Thalidomide, lenalidomide (Revlimid), and bortezomib (Velcade) are directed not only at MM cells but also at the BM milieu and have moved rapidly from the bench to the bedside and United States Food and Drug Administration approval to treat MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17996589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Lenalidomide (CC-5013, Revlimid; Celgene Corporation, Summit, NJ), a thalidomide analogue, was granted approval by the U.S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18922829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Lenalidomide, an IMiD drug (a novel type of immunomodulating drug) was recently approved by the US Food and Drug Administration for the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) and interstitial deletions of chromosome 5q [del(5q)]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17242661", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 537, "text": "Lenalidomide, a second-generation immunomodulatory drug (IMiD), is approved by the US Food and Drug Administration for treatment of transfusion-dependent anemia in lower-risk MDS patients with deletion 5q chromosomal abnormality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20425391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25188481", "endSection": "abstract" }, { "offsetInBeginSection": 35, "offsetInEndSection": 129, "text": "lenalidomide (CC5103 or revlimid) are recently approved for the treatment of multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 462, "text": " In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25188483", "endSection": "abstract" } ] }, { "body": "Which is the execution time (complexity) of the Smith-Waterman algorithm for the alignment of two sequences", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16522182", "http://www.ncbi.nlm.nih.gov/pubmed/14668231", "http://www.ncbi.nlm.nih.gov/pubmed/12804086", "http://www.ncbi.nlm.nih.gov/pubmed/11301301", "http://www.ncbi.nlm.nih.gov/pubmed/9021270", "http://www.ncbi.nlm.nih.gov/pubmed/1774068", "http://www.ncbi.nlm.nih.gov/pubmed/20370891", "http://www.ncbi.nlm.nih.gov/pubmed/21714130" ], "ideal_answer": [ "The complexity of the Smith-Waterman dynamic programming algorithm is quadratic, that is, it runs in time proportional to the product of lengths of the sequences being aligned." ], "exact_answer": [ "quadratic" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016415", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017385", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056510", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017386" ], "type": "factoid", "id": "51724fca8ed59a060a000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The problem of finding an optimal structural alignment for a pair of superimposed proteins is often amenable to the Smith-Waterman dynamic programming algorithm, which runs in time proportional to the product of lengths of the sequences being aligned.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21714130", "endSection": "sections.0" }, { "offsetInBeginSection": 531, "offsetInEndSection": 781, "text": "While this result is not an asymptotic improvement over the original Smith-Waterman algorithm, its complexity is characterized in terms of some sparse features of the matrix and it yields the fastest software implementation to date for such searches.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12804086", "endSection": "sections.0" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1804, "text": "If we use N, M and C to represent the size of an amino acid sequence, the size of a structure template, and the maximum cut size of long-range interactions, respectively, the algorithm finds an optimal structure-sequence alignment in O(21C NM) time, a polynomial function of N and M when C = O(log(N + M)). When running on structure-sequence alignment problems without long-range intersections, i.e. C = 0, the algorithm achieves the same asymptotic computational complexity of the Smith-Waterman sequence-sequence alignment algorithm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9021270", "endSection": "sections.0" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1470, "text": "The algorithm is based on fractional programming and its running time is O(n2log n). In practice, normalized local alignment is only 3-5 times slower than the standard Smith-Waterman algorithm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301301", "endSection": "sections.0" } ] }, { "body": "List mutations that are implicated in the Gray Platelet Syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23861251", "http://www.ncbi.nlm.nih.gov/pubmed/25258341", "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "http://www.ncbi.nlm.nih.gov/pubmed/21765413", "http://www.ncbi.nlm.nih.gov/pubmed/21765412", "http://www.ncbi.nlm.nih.gov/pubmed/23100277" ], "ideal_answer": [ "GFI1B and NBEAL2 mutations are implicated in the Gray Platelet Syndrome." ], "exact_answer": [ [ "GFI1B" ], [ "NBEAL2" ] ], "type": "list", "id": "56bcc455d36b5da378000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "A dominant-negative GFI1B mutation in the gray platelet syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "title" }, { "offsetInBeginSection": 145, "offsetInEndSection": 314, "text": "We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 280, "text": "The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 302, "text": "Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of \u03b1-granules within blood platelets and progressive bone marrow fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet \u03b1-granules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21765412", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21765413", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 493, "text": "Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of \u03b1-granules within blood platelets and progressive bone marrow fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258341", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 402, "text": "The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 896, "text": "Our studies show that GFI1B, in addition to being causally related to the gray platelet syndrome, is key to megakaryocyte and platelet development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "A dominant-negative GFI1B mutation in the gray platelet syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "title" }, { "offsetInBeginSection": 313, "offsetInEndSection": 482, "text": "We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 283, "text": "GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23861251", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 370, "text": "Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21765412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": " The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (\u03b1)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (\u03b1)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "The gray platelet syndrome is a hereditary, usually autosomal recessive bleeding disorder caused by a deficiency of alpha granules in platelets. We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 169, "text": "Mutations in NBEAL2 underlie gray platelet syndrome (GPS),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": " The gray platelet syndrome is a hereditary, usually autosomal recessive bleeding disorder caused by a deficiency of alpha granules in platelets. We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "abstract" } ] }, { "body": "Has single guide RNA been used on human cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24336569", "http://www.ncbi.nlm.nih.gov/pubmed/23873081", "http://www.ncbi.nlm.nih.gov/pubmed/25122746", "http://www.ncbi.nlm.nih.gov/pubmed/25048165", "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "http://www.ncbi.nlm.nih.gov/pubmed/24870050", "http://www.ncbi.nlm.nih.gov/pubmed/24770324", "http://www.ncbi.nlm.nih.gov/pubmed/23907171", "http://www.ncbi.nlm.nih.gov/pubmed/23940360", "http://www.ncbi.nlm.nih.gov/pubmed/23999092", "http://www.ncbi.nlm.nih.gov/pubmed/25759096" ], "ideal_answer": [ "Yes, sgRNA has been used in human cell lines." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017394" ], "type": "yesno", "id": "56f1547c2ac5ed1459000010", "snippets": [ { "offsetInBeginSection": 597, "offsetInEndSection": 719, "text": "We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336569", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 583, "text": "Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The type II CRISPR/Cas system from Streptococcus pyogenes and its simplified derivative, the Cas9/single guide RNA (sgRNA) system, have emerged as potent new tools for targeted gene knockout in bacteria, yeast, fruit fly, zebrafish and human cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23999092", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 355, "text": "Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907171", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 629, "text": "Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25048165", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 355, "text": "Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907171", "endSection": "abstract" } ] }, { "body": "Is Fibroblast Growth Factor 23 a phosphaturic hormone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24991914", "http://www.ncbi.nlm.nih.gov/pubmed/24466013", "http://www.ncbi.nlm.nih.gov/pubmed/25380933", "http://www.ncbi.nlm.nih.gov/pubmed/24434184", "http://www.ncbi.nlm.nih.gov/pubmed/25007710", "http://www.ncbi.nlm.nih.gov/pubmed/24980542", "http://www.ncbi.nlm.nih.gov/pubmed/25636143", "http://www.ncbi.nlm.nih.gov/pubmed/25404658", "http://www.ncbi.nlm.nih.gov/pubmed/26131357" ], "ideal_answer": [ "Yes, fbroblast growth factor 23 (FGF23) is a phosphaturic hormone." ], "exact_answer": "yes", "type": "yesno", "id": "570a5c27cf1c325851000023", "snippets": [ { "offsetInBeginSection": 498, "offsetInEndSection": 609, "text": "PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26131357", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1114, "text": " Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that has recently been identified as a CKD-related factor affecting CRS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636143", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1148, "text": " circulating phosphaturic hormone fibroblast growth factor-23 levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404658", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 199, "text": " Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25380933", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 179, "text": "fibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24466013", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 368, "text": "fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24434184", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 264, "text": " the phosphaturic hormone fibroblast growth factor 23 (FGF23) and soluble Klotho with all-cause mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991914", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 713, "text": "In particular, diseases caused by changes in the expression and proteolytic control of the phosphaturic hormone fibroblast growth factor-23 (FGF23) have come to the forefront in terms of directing new models explaining mineral metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980542", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 864, "text": "serum levels of a phosphaturic hormone, fibroblast growth factor 23 (Fgf23), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25007710", "endSection": "abstract" } ] }, { "body": "Which type of cell death is known as anoikis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23830918", "http://www.ncbi.nlm.nih.gov/pubmed/18579285", "http://www.ncbi.nlm.nih.gov/pubmed/20577896", "http://www.ncbi.nlm.nih.gov/pubmed/23357260", "http://www.ncbi.nlm.nih.gov/pubmed/21114588", "http://www.ncbi.nlm.nih.gov/pubmed/15302871", "http://www.ncbi.nlm.nih.gov/pubmed/25549223", "http://www.ncbi.nlm.nih.gov/pubmed/19828453", "http://www.ncbi.nlm.nih.gov/pubmed/18672025", "http://www.ncbi.nlm.nih.gov/pubmed/21953325", "http://www.ncbi.nlm.nih.gov/pubmed/21352421", "http://www.ncbi.nlm.nih.gov/pubmed/20153362", "http://www.ncbi.nlm.nih.gov/pubmed/20031162", "http://www.ncbi.nlm.nih.gov/pubmed/14551156", "http://www.ncbi.nlm.nih.gov/pubmed/19062038", "http://www.ncbi.nlm.nih.gov/pubmed/22505926", "http://www.ncbi.nlm.nih.gov/pubmed/18045538", "http://www.ncbi.nlm.nih.gov/pubmed/18719379", "http://www.ncbi.nlm.nih.gov/pubmed/14702756", "http://www.ncbi.nlm.nih.gov/pubmed/20670956" ], "ideal_answer": [ "Anoikis (Greek for Homelessness) is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonizing of distant organs. Anoikis is important in the normal physiologic development of the human body, as well as in disease states. Adhesion to structural glycoproteins of the extracellular matrix is necessary for survival of the differentiated adherent cells. Cancer cells harbor anoikis resistance allowing spread to occur.", "Ano?kis is defined as programmed cell death induced by the loss of cell/matrix interactions. Adhesion to structural glycoproteins of the extracellular matrix is necessary for survival of the differentiated adherent cells in the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts, and cardiac myocytes.Developed organs display strict spatial organization of differentiated cells which is required for proper organ function. One important device that prevents tissue disorganization is the death of cells that lose anchorage to their native matrix, a signal that indicates potential loss of proper tissue context. Termed anoikis (Greek for Homelessness), this form of cell death is a specialized form of apoptosis." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000209", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008219", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016265", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010941", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043276" ], "type": "summary", "id": "5525317687ecba3764000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "As a barrier to metastasis of cancer, cells that lost contact with the neighbouring cells or extracellular matrix(Extracellular matrix, ECM) will be subjected to apoptosis. This cell death process has been termed \"anoikis\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357260", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 417, "text": "When normal epithelial cells or solid tumor cells without metastatic potential detach from the primary site, and then enter into the circulatory system, the anoikis mechanism will be activated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357260", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 539, "text": "The significance of anoikis is to prevent the shedding cells from growing and implanting into other inappropriate sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonizing of distant organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830918", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 357, "text": "As a barrier to metastasis, cells normally undergo an apoptotic process known as \"anoikis,\" a form of cell death due to loss of contact with the extracellular matrix or neighboring cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 377, "text": "Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Detachment from the extracellular matrix induces a form of programmed cell death termed anoikis. Resistance to anoikis permits cancer cells to survive in systemic circulation and facilitates their metastasis to distant organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21352421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Anoikis - apoptotic cell death triggered by loss of extracellular matrix (ECM) contacts - is dysregulated in many chronic debilitating and fatal diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21114588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "The extracellular matrix (ECM) plays a key role in cell-cell communication and signaling, and the signals it propagates are important for tissue remodeling and survival. However, signals from disease-altered ECM may lead to anoikis-apoptotic cell death triggered by loss of ECM contacts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20577896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Anoikis is a mode of apoptotic cell death, consequential to insufficient cell-matrix interactions and a critical player in tumor angiogenesis and metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20153362", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1258, "text": "Anoikis is also a physiologic process in normal cells used to maintain homeostasis, in which cell death is induced in response to loss of extracellular membrane (ECM) attachment. Cancer cells are notoriously resistant to anoikis, enabling metastasis and new tumor growth beyond their original environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20031162", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 245, "text": "Anoikis is a subtype of apoptosis induced by detachment of adherent cells from the extracellular matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19828453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 411, "text": "Developed organs display strict spatial organization of differentiated cells which is required for proper organ function. One important device that prevents tissue disorganization is the death of cells that lose anchorage to their native matrix, a signal that indicates potential loss of proper tissue context. Termed anoikis (Greek for Homelessness), this form of cell death is a specialized form of apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18719379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "As a barrier to metastases, cells normally undergo apoptosis after they lose contact with their extra cellular matrix or their neighbouring cells. This cell death process has been termed \"anoikis\". Tumour cells that acquire malignant potential have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site and while travelling through the lymphatic and circulatory systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18579285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Epithelial cells require attachment to extracellular matrix (ECM) to suppress an apoptotic cell death program termed anoikis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, known as anoikis. Integrin stimulation protects cells from anoikis, but the responsible mechanisms are not well known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15302871", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 536, "text": "Apoptosis triggered by cell detachment from the extracellular matrix, which occurs during hepatocyte isolation, is a phenomenon termed \"anoikis\". It's importance in the normal physiologic development of the human body, as well as in disease states, has been described. Cancer cells harbor anoikis resistance allowing spread to occur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14702756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Ano\u00efkis is defined as programmed cell death induced by the loss of cell/matrix interactions. Adhesion to structural glycoproteins of the extracellular matrix is necessary for survival of the differentiated adherent cells in the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts, and cardiac myocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14551156", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 739, "text": "Adhesion is also a key factor for the differentiation of mesenchymal stem cells. In particular, fibronectin is considered a factor of survival and differentiation for many adherent cells. Adhesion generates cell tensional integrity (tensegrity) and repression of apoptotic signals, whereas detachment has the opposite effect. Ano\u00efkis plays a physiological role by regulating cell homeostasis in tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14551156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Anoikis is a special type of programmed cell death after loss of cell-cell and cell-extracellular matrix interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19062038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Detachment-induced cell death, or anoikis, is a type of apoptosis that occurs when epithelial cells lose their attachment to the extracellular matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Anoikis is a type of apoptosis due to the detachment from the extracellular matrix and neighboring cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18672025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, known as anoikis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15302871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonization of distant organs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25549223", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 356, "text": "As a barrier to metastasis, cells normally undergo an apoptotic process known as \"anoikis,\" a form of cell death due to loss of contact with the extracellular matrix or neighboring cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, known as anoikis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15302871", "endSection": "abstract" } ] }, { "body": "The small molecule SEA0400 is an inhibitor of which ion antiporter/exchanger?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19593760", "http://www.ncbi.nlm.nih.gov/pubmed/15556149", "http://www.ncbi.nlm.nih.gov/pubmed/22075452", "http://www.ncbi.nlm.nih.gov/pubmed/18855935", "http://www.ncbi.nlm.nih.gov/pubmed/15678087", "http://www.ncbi.nlm.nih.gov/pubmed/22119380", "http://www.ncbi.nlm.nih.gov/pubmed/21672583", "http://www.ncbi.nlm.nih.gov/pubmed/15703202", "http://www.ncbi.nlm.nih.gov/pubmed/17310075", "http://www.ncbi.nlm.nih.gov/pubmed/16842776", "http://www.ncbi.nlm.nih.gov/pubmed/15878358", "http://www.ncbi.nlm.nih.gov/pubmed/16497099", "http://www.ncbi.nlm.nih.gov/pubmed/11877314", "http://www.ncbi.nlm.nih.gov/pubmed/19423954", "http://www.ncbi.nlm.nih.gov/pubmed/20447431", "http://www.ncbi.nlm.nih.gov/pubmed/17727839", "http://www.ncbi.nlm.nih.gov/pubmed/16495765", "http://www.ncbi.nlm.nih.gov/pubmed/15231867", "http://www.ncbi.nlm.nih.gov/pubmed/23441899", "http://www.ncbi.nlm.nih.gov/pubmed/21903118", "http://www.ncbi.nlm.nih.gov/pubmed/16960421", "http://www.ncbi.nlm.nih.gov/pubmed/11408549" ], "ideal_answer": [ "The effects of SEA0400, a selective inhibitor of the Na(+)/Ca(2+) exchanger (NCX), on Na(+)-dependent Ca(2+) uptake and catecholamine (CA) release were examined in bovine adrenal chromaffin cells that were loaded with Na(+) by treatment with ouabain and veratridine. SEA0400 inhibited Na(+)-dependent (45)Ca(2+) uptake and CA release, with the IC(50) values of 40 and 100 nM, respectively. ", "SEA0400 is a selective inhibitor of the Na(+)/Ca(2+) exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na(+)/Ca(2+) exchanger. SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy] phenoxy]-5-ethoxyaniline), is a selective NCX inhibitor in vivo." ], "exact_answer": [ "Na(+)/Ca(2+) exchanger", "NCX" ], "type": "factoid", "id": "5506c3e38e1671127b00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "The plasma membrane Na(+)/Ca(2+) exchanger (NCX) is a bidirectional ion transporter that couples the translocation of Na(+) in one direction with that of Ca(2+) in the opposite direction. This system contributes to the regulation of intracellular Ca(2+) concentration via the forward mode (Ca(2+) efflux) or the reverse mode (Ca(2+) influx).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23441899", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1161, "text": "Concerning the role of NCX in NO cytotoxicity, we have found, using the specific inhibitor of NCX 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), that NCX is involved in NO-induced cytotoxicity in cultured microglia, astrocytes, and neuronal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23441899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "The Na(+)/Ca(2+)exchanger (NCX) principal function is taking 1 Ca(2+) out of the cytoplasm and introducing 3 Na(+). The increase of cytoplasmic Na(+) concentration induces the NCX reverse mode (NCX(REV)), favoring Ca(2+) influx. NCX(REV) can be inhibited by: KB-R7943 a non-specific compound that blocks voltage-dependent and store-operated Ca(2+) channels; SEA0400 that appears to be selective for NCX(REV), but difficult to obtain and SN-6, which efficacy has been shown only in cardiomyocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22119380", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1187, "text": "SEA0400 (1 \u03bcM), a pharmacological inhibitor of NCX, significantly shortened the MAP duration (P < .01) and reduced dispersion (P < .05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 575, "text": "We have recently shown that the Na(+)/Ca(2+) exchanger (NCX) is involved in nitric oxide (NO)-induced cytotoxicity in cultured astrocytes and neurons. However, there is no in vivo evidence suggesting the role of NCX in neurodegenerative disorders associated with NO. NO is implicated in the pathogenesis of neurodegenerative disorders such as Parkinson's disease. This study examined the effect of SEA0400, the specific NCX inhibitor, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity, a model of Parkinson's disease, in C57BL/6J mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 626, "text": "The Na(+)/Ca(2+) exchanger (NCX) plays a role in the regulation of intracellular Ca(2+) levels, and nitric oxide (NO) is involved in many pathological conditions including neurodegenerative disorders. We have previously found that sodium nitroprusside (SNP), an NO donor, causes apoptotic-like cell death in cultured glial cells via NCX-mediated pathways and the mechanism for NO-induced cytotoxicity is cell type-dependent. The present study examined using the specific NCX inhibitor 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) whether NCX is involved in NO-induced injury in cultured neuronal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21672583", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 690, "text": "In view of the previous observation that NO stimulates the activity of the Na(+)/Ca(2+) exchanger (NCX), this study examines the involvement of NCX in cytotoxicity. The specific NCX inhibitor SEA0400 blocked SNP-induced phosphorylation of ERK, JNK and p38 MAPK, and decrease in cell viability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20447431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 533, "text": "The sodium-calcium exchanger (NCX) is one of the transporters contributing to the control of intracellular calcium (Ca(2+)) concentration by normally mediating net Ca(2+) efflux. However, the reverse mode of the NCX can cause intracellular Ca(2+) concentration overload, which exacerbates the myocardial tissue injury resulting from ischemia. Although the NCX inhibitor SEA0400 has been shown to therapeutically reduce myocardial injury, no in vivo technique exists to monitor intracellular Ca(2+) fluctuations produced by this drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19593760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "We examined the involvement of the Na(+)/Ca(2+) exchanger in the automaticity of the pulmonary vein myocardium with a specific inhibitor, SEA0400.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19423954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "We investigated the expression of Na(+)/Ca(2+) exchanger (NCX) and the functional role of NCX in retinal damage by using NCX1-heterozygous deficient mice (NCX1(+/-)) and SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy] phenoxy]-5-ethoxyaniline), a selective NCX inhibitor in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18855935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "SEA0400 is a selective inhibitor of the Na(+)/Ca(2+) exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na(+)/Ca(2+) exchanger.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17727839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Involvement of the Na+/Ca2+ exchanger in ouabain-induced inotropy and arrhythmogenesis was examined with a specific inhibitor, SEA0400.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17310075", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 431, "text": "In right ventricular papillary muscle isolated from guinea-pig ventricle, 1 microM SEA0400, which specifically inhibits the Na+/Ca2+ exchanger by 80%, reduced the ouabain (1 microM)-induced positive inotropy by 40%, but had no effect on the inotropy induced by 100 microM isobutyl methylxantine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17310075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "The effects of SEA0400, a selective inhibitor of the Na(+)/Ca(2+) exchanger (NCX), on Na(+)-dependent Ca(2+) uptake and catecholamine (CA) release were examined in bovine adrenal chromaffin cells that were loaded with Na(+) by treatment with ouabain and veratridine. SEA0400 inhibited Na(+)-dependent (45)Ca(2+) uptake and CA release, with the IC(50) values of 40 and 100 nM, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16960421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 482, "text": "Given the potential clinical benefit of inhibiting Na+/Ca2+ exchanger (NCX) activity during myocardial ischemia reperfusion (I/R), pharmacological approaches have been pursued to both inhibit and clarify the importance of this exchanger. SEA0400 was reported to have a potent NCX selectivity. Thus, we examined the effect of SEA0400 on NCX currents and I/R induced intracellular Ca2+ overload in mouse ventricular myocytes using patch clamp techniques and fluorescence measurements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16497099", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1349, "text": "The results suggested that SEA0400 is a potent NCX inhibitor, which can protect mouse cardiac myocytes from Ca2+ overload during I/R injuries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16497099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The effect of SEA0400, a novel Na+-Ca2+ exchanger inhibitor, on mechanical and electrophysiological parameters of coronary-perfused guinea-pig right ventricular tissue preparation was examined during no-flow ischemia and reperfusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15878358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "The Ca2+ overload by Ca2+ influx via Na+/Ca2+ exchanger (NCX) is a critical mechanism in myocardial ischemia/reperfusion injury. We investigated protective effects of a novel selective inhibitor of NCX, SEA0400, on cardiac function and energy metabolism during ischemia and reperfusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16495765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The cardioprotective effects of SEA0400, a novel Na(+)-Ca(2+) exchanger inhibitor, were examined in isolated guinea pig myocardial tissue and ventricular myocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16842776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "The effects of a new, potent, and selective inhibitor of the Na(+)/Ca(2+) exchange, SEA-0400 (SEA), on steady-state outward (forward exchange), inward (reverse exchange), and Ca(2+)/Ca(2+) transport exchange modes were studied in internally dialyzed squid giant axons from both the extra- and intracellular sides. Inhibition by SEA takes place preferentially from the intracellular side of the membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703202", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 256, "text": "Using SEA0400, a potent and selective inhibitor of the Na+-Ca2+ exchanger (NCX), we examined whether NCX is involved in nitric oxide (NO)-induced disturbance of endoplasmic reticulum (ER) Ca2+ homeostasis followed by apoptosis in cultured rat microglia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15678087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury (myocardial stunning).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15556149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline) has recently been described as a potent and selective inhibitor of Na(+)-Ca(2+) exchange in cardiac, neuronal, and renal preparations. The inhibitory effects of SEA0400 were investigated on the cloned cardiac Na(+)-Ca(2+) exchanger, NCX1.1, expressed in Xenopus laevis oocytes to gain insight into its inhibitory mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15231867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 780, "text": "The effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a newly synthesized Na(+)-Ca(2+) exchanger (NCX) inhibitor, on the NCX current and other membrane currents were examined in isolated guinea-pig ventricular myocytes and compared with those of 2-[2-[4-(4-nitrobenzyloxy) phenyl]ethyl]isothiourea (KB-R7943). SEA0400 concentration-dependently inhibited the NCX current with a 10 fold higher potency than that of KB-R7943; 1 microM SEA0400 and 10 microM KB-R7943 inhibited the NCX current by more than 80%. KB-R7943, at 10 microM, inhibited the sodium current, L-type calcium current, delayed rectifier potassium current and inwardly rectifying potassium current by more than 50%, but SEA0400 (1 microM) had no significant effect on these currents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11877314", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 997, "text": "These results indicate that SEA0400 is a potent and highly selective inhibitor of NCX, and would be a powerful tool for further studies on the role of NCX in the heart and the therapeutic potential of its inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11877314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "The effect of the newly synthesized compound 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) on the Na+-Ca2+ exchanger (NCX) was investigated and compared against that of 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11408549", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 850, "text": "In addition, the effects of SEA0400 on reperfusion injury in vitro and in vivo were examined. SEA0400 was extremely more potent than KB-R7943 in inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia: IC50s of SEA0400 and KB-R7943 were 5 to 33 nM and 2 to 4 microM, respectively. SEA0400 at the concentration range that inhibited NCX exhibited negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, norepinephrine transporter, and 14 receptors, and did not affect the activities of the Na+/H+ exchanger, Na+,K+-ATPase, Ca2+-ATPase, and five enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11408549", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1515, "text": "These results indicate that SEA0400 is the most potent and selective inhibitor of NCX, and suggest that the compound may exert protective effects on postischemic brain damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11408549", "endSection": "abstract" } ] }, { "body": "What is Piebaldism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11174389", "http://www.ncbi.nlm.nih.gov/pubmed/21382296", "http://www.ncbi.nlm.nih.gov/pubmed/20676476", "http://www.ncbi.nlm.nih.gov/pubmed/22670867", "http://www.ncbi.nlm.nih.gov/pubmed/23130293", "http://www.ncbi.nlm.nih.gov/pubmed/23016555", "http://www.ncbi.nlm.nih.gov/pubmed/20137753", "http://www.ncbi.nlm.nih.gov/pubmed/22438235", "http://www.ncbi.nlm.nih.gov/pubmed/23786947", "http://www.ncbi.nlm.nih.gov/pubmed/7529964", "http://www.ncbi.nlm.nih.gov/pubmed/12204004", "http://www.ncbi.nlm.nih.gov/pubmed/7525736" ], "ideal_answer": [ "Piebaldism is a rare autosomal dominant disorder of melanocyte development characterized by a congenital white forelock and multiple symmetrical stable hypopigmented or depigmented macules." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016116" ], "type": "summary", "id": "54fc4e2e6ea36a810c000003", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 139, "text": "Human piebaldism is a rare autosomal dominant condition characterized by congenital white forelock and depigmented patches of s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23786947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Piebaldism is a rare genodermatosis caused by KIT mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23016555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Piebaldism is a rare autosomal dominant disorder of melanocyte development characterized by a congenital white forelock and multiple symmetrical stable hypopigmented or depigmented macules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23130293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Piebaldism is an autosomal dominant disorder characterized by congenital hypopigmented patches of skin and hair and has been found to be associated with mutations in the KIT or SLUG genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Piebaldism is a rare autosomal dominant skin disorder characterized by a white forelock and depigmented patches of skin, generally located on the forehead, central chest and abdomen, upper arms, and lower extremities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21382296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Piebaldism is a rare genodermatosis in which depigmented skin areas are unresponsive to topical or light treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20676476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Piebaldism is a rare disorder present at birth and inherited as an autosomal dominant trait. It results from a mutation in the c-kit proto-oncogene and is associated with a defect in the migration and differentiation of melanoblasts from the neural crest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20137753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7529964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 436, "text": "Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KIT proto-oncogene, which encodes the cell-surface receptor transmembrane tyrosine kinase for an embryonic growth factor, Steel factor. Several pathologic mutations of the KIT gene have now been identified in different patients with piebaldism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7525736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Piebaldism is an autosomal dominant disorder of melanocyte development characterized by white skin (leukoderma) and white hair (poliosis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11174389", "endSection": "abstract" } ] }, { "body": "Which SLC family is FLVCR1 a member of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23506900" ], "ideal_answer": [ "Feline leukemia virus subgroup C receptor (FLVCR1) is a member of the SLC49 family." ], "exact_answer": [ "SLC49" ], "type": "factoid", "id": "56d85e7751531f7e33000001", "snippets": [ { "offsetInBeginSection": 136, "offsetInEndSection": 335, "text": "Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23506900", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 533, "text": "Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23506900", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 440, "text": "Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis. Disruption of FLVCR1 function blocks development of erythroid progenitors, likely due to heme toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23506900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": " Heme is critical for a variety of cellular processes, but excess intracellular heme may result in oxidative stress and membrane injury. Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23506900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Heme is critical for a variety of cellular processes, but excess intracellular heme may result in oxidative stress and membrane injury. Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23506900", "endSection": "abstract" } ] }, { "body": "Is amoxicillin used for treatment of malnutrition in children?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23326395", "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "http://www.ncbi.nlm.nih.gov/pubmed/21836758", "http://www.ncbi.nlm.nih.gov/pubmed/23755286", "http://www.ncbi.nlm.nih.gov/pubmed/23363496", "http://www.ncbi.nlm.nih.gov/pubmed/18318945" ], "ideal_answer": [ "Yes, amoxicillin is used for treatment of malnutrition in children." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002648", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044342", "http://www.biosemantics.org/jochem#4248866", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000658", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4248866", "http://www.biosemantics.org/jochem#4134180" ], "type": "yesno", "id": "56bb69d0ac7ad1001900000c", "snippets": [ { "offsetInBeginSection": 879, "offsetInEndSection": 1478, "text": " Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p\u200a=\u200a0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27-55%) vs 22% (IQR 17-23%) and population-weighted-means 52.9% (range 23-57%) vs 35.4% (range 6.7-42%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326395", "endSection": "abstract" }, { "offsetInBeginSection": 1812, "offsetInEndSection": 1875, "text": " Susceptibility-studies favour amoxicillin over cotrimoxazole. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326395", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 918, "text": "Oral amoxicillin for 5\u00a0days was as effective as intramuscular ceftriaxone for 2\u00a0days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21836758", "endSection": "abstract" }, { "offsetInBeginSection": 1658, "offsetInEndSection": 1864, "text": "Children who took amoxicillin and de-worming had 95% (HR\u200a=\u200a1.95, 95%-CI\u200a=\u200a1.17, 3.23) and 74% (HR\u200a=\u200a1.74, 95%-CI\u200a=\u200a1.07, 2.83) more probability to recover from SAM as compared to those who didn't take them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23755286", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 610, "text": "METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23363496", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 1304, "text": "In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23363496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "OBJECTIVE: To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 457, "text": "The standard protocol group received a 7-day course of amoxicillin at the onset of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 882, "text": "RESULTS: Four hundred and ninety-eight children were treated according to the standard protocol with amoxicillin, and 1955 were treated under the alternate protocol without antibiotics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1179, "text": "The recovery rate for children who received amoxicillin was worse at 4 weeks (40%vs. 71%) but similar after up to 12 weeks of therapy (84%vs. 86%), compared to the children treated without antibiotics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1500, "text": "CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Treatment of severe malnutrition with 2-day intramuscular ceftriaxone vs 5-day amoxicillin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18318945", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "OBJECTIVE: To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food. METHODS: This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6-59 months with uncomplicated severe acute malnutrition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1506, "text": "The recovery rate for children who received amoxicillin was worse at 4 weeks (40%vs. 71%) but similar after up to 12 weeks of therapy (84%vs. 86%), compared to the children treated without antibiotics. Regression modelling indicated that this difference at 4 weeks was most strongly associated with the receipt of amoxicillin. CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1506, "text": "CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545919", "endSection": "abstract" } ] }, { "body": "Where are the orexigenic peptides synthesized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22771813", "http://www.ncbi.nlm.nih.gov/pubmed/21903140", "http://www.ncbi.nlm.nih.gov/pubmed/25258168", "http://www.ncbi.nlm.nih.gov/pubmed/23707377", "http://www.ncbi.nlm.nih.gov/pubmed/22325091", "http://www.ncbi.nlm.nih.gov/pubmed/24991043", "http://www.ncbi.nlm.nih.gov/pubmed/25241055", "http://www.ncbi.nlm.nih.gov/pubmed/25047666", "http://www.ncbi.nlm.nih.gov/pubmed/25017744", "http://www.ncbi.nlm.nih.gov/pubmed/22922128", "http://www.ncbi.nlm.nih.gov/pubmed/25039297", "http://www.ncbi.nlm.nih.gov/pubmed/25502749", "http://www.ncbi.nlm.nih.gov/pubmed/21574955" ], "ideal_answer": [ "The orexigenic peptides are sythesized in the hypothalamus." ], "exact_answer": [ "The orexigenic peptides are sythesized in the hypothalamus." ], "type": "factoid", "id": "56e47e0051531f7e3300001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Orexin A and B, orexigenic peptides produced primarily by the lateral hypothalamus t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25502749", "endSection": "abstract" }, { "offsetInBeginSection": 1409, "offsetInEndSection": 1528, "text": "Telmisartin reduced hypothalamic mRNA levels of the orexigenic peptides melanin-concentrating hormone and prepro-orexin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258168", "endSection": "abstract" }, { "offsetInBeginSection": 1517, "offsetInEndSection": 1636, "text": "expression of the orexigenic peptides, enkephalin (ENK) and galanin (GAL), in developing embryonic hypothalamic neurons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25039297", "endSection": "abstract" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1536, "text": "hypothalamic orexigenic peptides,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991043", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 418, "text": " Such mechanisms may involve orexigenic peptides known to stimulate alcohol intake through their actions in the hypothalamic paraventricular nucleus (PVN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25241055", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1296, "text": "hypothalamus orexigenic peptides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25017744", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 585, "text": " the hypothalamic mRNA expression of endogenous orexigenic peptides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25047666", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 329, "text": "The hypothalamus integrates peripheral and central signals to generate satiety or hunger. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707377", "endSection": "abstract" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1054, "text": "increase in mRNA expression of hypothalamic orexigenic peptides and a decrease of anorexigenic peptides;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22771813", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 772, "text": "expression of the orexigenic peptides, galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) and orexin (OX) in the perifornical lateral hypothalamus (PFLH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903140", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 883, "text": "Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22325091", "endSection": "abstract" }, { "offsetInBeginSection": 38, "offsetInEndSection": 71, "text": "hypothalamic orexigenic peptides ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922128", "endSection": "title" } ] }, { "body": "What is the mechanism of action of APOBEC3G cytidine deaminase to inhibit HIV-1 replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23152537", "http://www.ncbi.nlm.nih.gov/pubmed/22787460", "http://www.ncbi.nlm.nih.gov/pubmed/24651717", "http://www.ncbi.nlm.nih.gov/pubmed/17126871", "http://www.ncbi.nlm.nih.gov/pubmed/24623435", "http://www.ncbi.nlm.nih.gov/pubmed/24345943", "http://www.ncbi.nlm.nih.gov/pubmed/24859335" ], "ideal_answer": [ "During reverse transcription, APOBEC3G deaminates dC to dU in nascent minus-strand viral DNA, resulting in G-to-A hypermutation in the plus strand DNA to inhibit replication of HIV-1, due to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. In an additional line of antiviral defense, APOBEC3G induces deamination of the apical loop cytidine of the trans-activation response (TAR) element, a short stem-loop RNA structure required for binding of elongation factors during HIV-1 transcription elongation, resulting in accumulation of short viral transcripts and production of lower amounts of full-length HIV-1 transcripts in Vif-deficient HIV-1-infected cells." ], "concepts": [ "http://www.uniprot.org/uniprot/ABC3G_PANTR", "http://www.uniprot.org/uniprot/ABC3G_CHLAE", "http://www.uniprot.org/uniprot/ABC3G_MACFA", "http://www.uniprot.org/uniprot/ABC3G_LAGLA", "http://www.uniprot.org/uniprot/ABC3G_PAPAN", "http://www.uniprot.org/uniprot/ABC3G_GORGO", "http://www.uniprot.org/uniprot/ABC3G_MACMU", "http://www.uniprot.org/uniprot/ABC3G_PONPY", "http://www.uniprot.org/uniprot/ABC3G_SAGLB", "http://www.uniprot.org/uniprot/ABC3G_ERYPA" ], "type": "summary", "id": "54dfcdf81388e8454a00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859335", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859335", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 933, "text": "HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "The APOBEC3 deoxycytidine deaminase family functions as host restriction factors that can block replication of Vif (virus infectivity factor) deficient HIV-1 virions to differing degrees by deaminating cytosines to uracils in single-stranded (-)HIV-1 DNA. Upon replication of the (-)DNA to (+)DNA, the HIV-1 reverse transcriptase incorporates adenines opposite the uracils, thereby inducing C/G\u2192T/A mutations that can functionally inactivate HIV-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24651717", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 409, "text": "APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24345943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4(+) T cells is associated with inhibition of processive reverse transcription as well as excessive cytidine deamination", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152537", "endSection": "title" }, { "offsetInBeginSection": 157, "offsetInEndSection": 332, "text": "These proteins exert their suppressive effects through the inhibition of viral reverse transcription as well as the induction of cytidine deamination within nascent viral cDNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152537", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 969, "text": "We demonstrate that APOBEC3 proteins impart a profound deficiency to reverse transcription from the initial stages of cDNA synthesis, as well as excessive cytidine deamination (hypermutation) of the DNAs that are synthesized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152537", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 771, "text": "Without Vif, A3 proteins, particularly APOBEC3G (A3G) and APOBEC3F (A3F), inhibit HIV-1 replication by blocking reverse transcription and/or integration and hypermutating nascent viral cDNA. The molecular mechanisms of this antiviral activity have been primarily attributed to two biochemical characteristics common to A3 proteins: catalyzing cytidine deamination in single-stranded DNA (ssDNA) and a nucleic acid-binding capability that is specific to ssDNA or ssRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "A host cytidine deaminase, APOBEC3G (A3G), inhibits replication of human immunodeficiency virus type 1 (HIV-1) by incorporating into virions in the absence of the virally encoded Vif protein (Deltavif virions), at least in part by causing G-to-A hypermutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17126871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "APOBEC3F and APOBEC3G cytidine deaminases potently inhibit human immunodeficiency virus type 1 (HIV-1) replication by enzymatically inserting G-to-A mutations in viral DNA and/or impairing viral reverse transcription independently of their deaminase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24623435", "endSection": "abstract" } ] }, { "body": "Which inherited disorder is known to be caused by mutations in the NEMO gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22036144", "http://www.ncbi.nlm.nih.gov/pubmed/19149237", "http://www.ncbi.nlm.nih.gov/pubmed/16532398", "http://www.ncbi.nlm.nih.gov/pubmed/18350553", "http://www.ncbi.nlm.nih.gov/pubmed/23378396", "http://www.ncbi.nlm.nih.gov/pubmed/22236433", "http://www.ncbi.nlm.nih.gov/pubmed/20434027", "http://www.ncbi.nlm.nih.gov/pubmed/20499091", "http://www.ncbi.nlm.nih.gov/pubmed/23405946", "http://www.ncbi.nlm.nih.gov/pubmed/17569396", "http://www.ncbi.nlm.nih.gov/pubmed/15833158", "http://www.ncbi.nlm.nih.gov/pubmed/22121116", "http://www.ncbi.nlm.nih.gov/pubmed/16104114", "http://www.ncbi.nlm.nih.gov/pubmed/24339369", "http://www.ncbi.nlm.nih.gov/pubmed/10911992" ], "ideal_answer": [ "Incontinentia pigmenti (IP) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait", "Incontinentia pigmenti (IP) or Bloch-Sulzberger syndrome (BSS) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait." ], "exact_answer": [ "Incontinentia pigmenti or Bloch-Sulzberger syndrome" ], "type": "factoid", "id": "5721f4b30fd6f91b68000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Incontinentia pigmenti (IP) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22036144", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 754, "text": "Mutations in the NEMO gene give rise to a heterogeneous group of disorders, including the X-linked dominant disorder incontinentia pigmenti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20499091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "De novo NEMO gene deletion (delta4-10)--a cause of incontinentia pigmenti in a female infant", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19149237", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Incontinentia pigmenti (IP) is a rare, inherited, multisystem genodermatosis. It is transmitted as an X-linked dominant trait. The disorder is a consequence of mutations in the NEMO gene (Xq28) that completely abolish expression of the NF-kappaB essential modulator", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19149237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 536, "text": "Incontinentia pigmenti (IP) is a rare inherited multisystem disorder characterized by a distinctive swirling pattern of the skin; defects of teeth, hair, and nails; and ophthalmic, central nervous system, and musculoskeletal abnormalities. It progresses through several well-defined stages. IP is transmitted as a dominant X-linked trait with variable expressivity, but many--if not most--cases are sporadic. IP has been shown to result from mutations in the NEMO gene that completely abolish expression of NF-kappaB essential modulator", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17569396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Incontinentia pigmenti (IP; MIM308310) is a rare neurocutaneous X-dominant inherited disorder. Besides skin and neurological abnormalities, there is also ophthalmologic and dental involvement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16104114", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 866, "text": "The disorder is observed almost exclusively in girls, but diseased boys are more seriously affected. The IP gene is localised on chromosome Xq28. Mutations in the NEMO-gene are responsible for IP. This gene codes for the nuclear factor-KB essential modulator protein (NEMO; synonym: inhibitor kappaB kinase (IKK)y)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16104114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Incontinentia pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of nuclear factor kappaB (NF-kB) signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339369", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 890, "text": "Mutations in the NEMO gene give rise to a heterogeneous group of disorders, including the X-linked dominant disorder incontinentia pigmenti.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20499091", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1218, "text": "In patients with incontinenia pigmenti, mutations in the NEMO gene are found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378396", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1332, "text": "Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23405946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "IKBKG/NEMO gene mutations cause an X-linked, dominant neuroectodermal disorder named Incontinentia Pigmenti (IP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22121116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "[NEMO Delta 4-10 deletion of NEMO gene in Chinese incontinentia pigmenti cases].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15833158", "endSection": "title" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1148, "text": "In patients with incontinenia pigmenti, mutations in the NEMO gene are found", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Amorphic mutations in the NF- kappa B essential modulator (NEMO) cause X-dominant incontinentia pigmenti, which is lethal in males in utero, whereas hypomorphic mutations cause X-recessive anhidrotic ectodermal dysplasia with immunodeficiency, a complex developmental disorder and life-threatening primary immunodeficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16532398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "NEMO gene mutations in Chinese patients with incontinentia pigmenti.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20434027", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "De novo NEMO gene deletion (delta4-10)--a cause of incontinentia pigmenti in a female infant: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19149237", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "Mutations in the inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), also called nuclear factor-kappaB (NF-kB) essential modulator (NEMO), gene are the most common single cause of incontinentia pigmenti (IP) in females and anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18350553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "NEMO/IKK gamma-deficient mice model incontinentia pigmenti.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10911992", "endSection": "title" }, { "offsetInBeginSection": 527, "offsetInEndSection": 884, "text": "Germline mutations in two genes, NEMO and CYBB, have long been known to cause other human diseases-incontinentia pigmenti (IP) and anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (NEMO/IKKG), and X-linked chronic granulomatous disease (CGD) (CYBB)-but specific mutations in either of these two genes have recently been shown to cause XR-MSMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22236433", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 756, "text": "Mutations in the NEMO gene give rise to a heterogeneous group of disorders, including the X-linked dominant disorder incontinentia pigmenti.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20499091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "IKBKG/NEMO gene mutations cause an X-linked, dominant neuroectodermal disorder named Incontinentia Pigmenti (IP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22121116", "endSection": "abstract" } ] }, { "body": "What is ISMARA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24515121" ], "ideal_answer": [ "ISMARA (Integrated System for Motif Activity Response Analysis) is a web-based tool that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites. Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles. These include predicted activities of the regulators across the samples, their genome-wide targets, enriched gene categories among the targets, and direct interactions between the regulators." ], "type": "summary", "id": "56accec70a360a5e45000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "title" }, { "offsetInBeginSection": 633, "offsetInEndSection": 1686, "text": "We developed a methodology that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites and completely automated it into a web-based tool called ISMARA (Integrated System for Motif Activity Response Analysis). Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles. These include predicted activities of the regulators across the samples, their genome-wide targets, enriched gene categories among the targets, and direct interactions between the regulators. Applying ISMARA to data sets from well-studied systems, we show that it consistently identifies known key regulators ab initio. We also present a number of novel predictions including regulatory interactions in innate immunity, a master regulator of mucociliary differentiation, TFs consistently disregulated in cancer, and TFs that mediate specific chromatin modifications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1343, "text": "Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" }, { "offsetInBeginSection": 889, "offsetInEndSection": 1148, "text": "We developed a methodology that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites and completely automated it into a web-based tool called ISMARA (Integrated System for Motif Activity Response Analysis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1441, "text": "Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles. These include predicted activities of the regulators across the samples, their genome-wide targets, enriched gene categories among the targets, and direct interactions between the regulators. Applying ISMARA to data sets from well-studied systems, we show that it consistently identifies known key regulators ab initio. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 893, "text": "Although gene expression and chromatin state dynamics are ultimately encoded by constellations of binding sites recognized by regulators such as transcriptions factors (TFs) and microRNAs (miRNAs), our understanding of this regulatory code and its context-dependent read-out remains very limited. Given that there are thousands of potential regulators in mammals, it is not practical to use direct experimentation to identify which of these play a key role for a particular system of interest. We developed a methodology that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites and completely automated it into a web-based tool called ISMARA (Integrated System for Motif Activity Response Analysis). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 1121, "text": "We developed a methodology that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites and completely automated it into a web-based tool called ISMARA (Integrated System for Motif Activity Response Analysis). Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1313, "text": "Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles. These include predicted activities of the regulators across the samples, their genome-wide targets, enriched gene categories among the targets, and direct interactions between the regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 893, "text": "Given that there are thousands of potential regulators in mammals, it is not practical to use direct experimentation to identify which of these play a key role for a particular system of interest. We developed a methodology that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites and completely automated it into a web-based tool called ISMARA (Integrated System for Motif Activity Response Analysis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24515121", "endSection": "abstract" } ] }, { "body": "Is it possible to purify pseudopodia to be used for proteomic analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22980730", "http://www.ncbi.nlm.nih.gov/pubmed/21909922", "http://www.ncbi.nlm.nih.gov/pubmed/23313222", "http://www.ncbi.nlm.nih.gov/pubmed/22751350", "http://www.ncbi.nlm.nih.gov/pubmed/17712138" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0107210", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0033827", "o": "http://linkedlifedata.com/resource/umls/label/A11597519" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1396549", "o": "pseudopod" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0449712", "o": "Pseudopodium" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0033827", "o": "http://linkedlifedata.com/resource/umls/label/A0449712" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0033827", "o": "http://linkedlifedata.com/resource/umls/label/A1396549" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0033827", "o": "http://linkedlifedata.com/resource/umls/label/A0107210" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11622199", "o": "pseudopodium" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0033827", "o": "http://linkedlifedata.com/resource/umls/label/A11622199" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0033827", "o": "http://linkedlifedata.com/resource/umls/label/A0107210" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0107210", "o": "Pseudopodia" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0449712", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11597519", "o": "Gene Ontology" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11622199", "o": "Gene Ontology" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0033827", "o": "http://linkedlifedata.com/resource/umls/id/C1622568" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11622225", "o": "pseudopodium membrane" }, { "p": "http://purl.uniprot.org/core/partOf", "s": "http://purl.uniprot.org/locations/471", "o": "http://purl.uniprot.org/locations/298" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/locations/298", "o": "Pseudopod" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0031143", "o": "pseudopodium" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/locations/298", "o": "Pseudopodium" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0031143", "o": "pseudopod" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/locations/471", "o": "Pseudopodium tip" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/locations/298", "o": "Pseudopodia" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0031143", "o": "http://www.geneontology.org/go#GO:0031143" }, { "p": "http://purl.uniprot.org/core/alias", "s": "http://purl.uniprot.org/locations/471", "o": "pseudopodium tip" } ], "ideal_answer": [ "Pseudopodia can be purified, using different strategies, in order to be used in proteomic studies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011554", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "yesno", "id": "52e01f8f98d023950500000f", "snippets": [ { "offsetInBeginSection": 484, "offsetInEndSection": 675, "text": "we developed an approach to biochemically isolate the pseudopodium from the cell body using 3.0-micrometer porous filters for large-scale quantitative proteomic and phosphoproteomic analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17712138", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 556, "text": "Recent work using unique subcellular fractionation methodologies combined with spatial genomic, proteomic, and phosphoproteomic profiling has provided insight into the invadopodiome and pseudopodiome signaling networks ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22980730", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 393, "text": "ere, we purified the pseudopodial proteomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23313222", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 665, "text": "tumor cells were placed on a fibronectin-coated porous membrane to form pseudopodia. According to the motile potentials of the cells, the cells formed pseudopodial microprocesses in the pores. An excimer laser, which was used for ophthalmic refractive surgeries, horizontally ablated cells at the membrane surface to remove the cell body. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22751350", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 954, "text": "we describe methods for the immunoaffinity purification of phosphotyrosine proteins (pY) from pseudopodia that have been isolated from migratory cells. These methods are compatible with current mass spectrometry-based protein identification technologies and can be utilized for the large-scale identification of the pseudopodium pY proteome in various migratory cell lines, including primary and cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21909922", "endSection": "abstract" } ] }, { "body": "Where does TDP43 localize in ALS neurons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19251627", "http://www.ncbi.nlm.nih.gov/pubmed/17481916" ], "ideal_answer": [ "In control motor neurons, TDP43 was almost exclusively nuclear, whereas in ALS spinal motor neurons, TDP43 was predominantly localized to the cytosol and not the nucleus. ", "In control motor neurons, TDP43 was almost exclusively nuclear, whereas in ALS spinal motor neurons, TDP43 was predominantly localized to the cytosol and not the nucleus." ], "type": "summary", "id": "56cad5df5795f9a73e000020", "snippets": [ { "offsetInBeginSection": 341, "offsetInEndSection": 512, "text": "In control motor neurons, TDP43 was almost exclusively nuclear, whereas in ALS spinal motor neurons, TDP43 was predominantly localized to the cytosol and not the nucleus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17481916", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 800, "text": "The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19251627", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 617, "text": "In control motor neurons, TDP43 was almost exclusively nuclear, whereas in ALS spinal motor neurons, TDP43 was predominantly localized to the cytosol and not the nucleus. TDP43 was observed as punctuate immunoreactivity and as dense skeins, with and without ubiquitinization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17481916", "endSection": "abstract" } ] }, { "body": "List interaction partners for the protein GATA1.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "http://www.ncbi.nlm.nih.gov/pubmed/21532337", "http://www.ncbi.nlm.nih.gov/pubmed/17108004", "http://www.ncbi.nlm.nih.gov/pubmed/18844071", "http://www.ncbi.nlm.nih.gov/pubmed/12032775", "http://www.ncbi.nlm.nih.gov/pubmed/20959602", "http://www.ncbi.nlm.nih.gov/pubmed/15542823", "http://www.ncbi.nlm.nih.gov/pubmed/15920471" ], "ideal_answer": [ "GATA-1 interact with factor Gfi-1b, the repressive MeCP1 complex, the chromatin remodeling ACF/WCRF complex, FOG-1, TAL-1, Ldb-1 and LMO2-C.", "GATA1 interacts with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. Ldb1 is a known partners of GATA1. LMO2-C can bind endogenous GATA1. Novel transcription factor binding partners for PIAS3 include GATA1. Combinatorial interactions occurre between RUNX1 and its coregulator GATA1. Ski interacts with GATA1. GATA-1 interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1." ], "exact_answer": [ [ "Gfi-1b" ], [ "MeCP1", "MeCP1 complex" ], [ "ACF/WCRF complex" ], [ "FOG-1" ], [ "TAL-1" ], [ "Ldb1", "Ldb-1" ], [ "LMO2-C" ], [ "PIAS3" ], [ "RUNX1" ], [ "Ski" ], [ "EKLF" ], [ "SP1" ], [ "CBP/p300" ], [ "PU.1" ] ], "concepts": [ "http://www.uniprot.org/uniprot/GATA1_RAT", "http://www.uniprot.org/uniprot/GATA1_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025941", "http://www.uniprot.org/uniprot/GATA1_ARATH", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054730", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060066", "http://www.uniprot.org/uniprot/GATA1_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050982", "http://www.uniprot.org/uniprot/GATA1_HUMAN" ], "type": "list", "id": "52f89fd32059c6d71c000051", "snippets": [ { "offsetInBeginSection": 752, "offsetInEndSection": 1519, "text": "Our work describes, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. We also provide evidence that distinct GATA-1 complexes are associated with specific GATA-1 functions in erythroid differentiation, for example, GATA-1/Gfi-1b with the suppression of cell proliferation and GATA-1/FOG-1/MeCP1 with the repression of other hematopoietic transcription programs. We next applied the biotinylation tag to Ldb-1, a known partner of GATA-1, and characterized a number of novel interaction partners that are essential in erythroid development, in particular, Eto-2, Lmo4, and CdK9. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 604, "text": "Endogenous GATA1 and LDB1 proteins were confirmed to bind to LMO2-C by MBP pull down analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18844071", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1053, "text": "LMO2-C can bind endogenous GATA1 and LDB1 protein in K562 cells and down regulates the expression of GPA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18844071", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 587, "text": "We identify novel transcription factor binding partners for PIAS3 including ETS, EGR1, NR1I2, and GATA1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21532337", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1301, "text": "At other differentiation stages, additional combinatorial interactions occurred between RUNX1 and its coregulators, GATA1 and ETS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20959602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Ldb1, a ubiquitously expressed LIM domain binding protein, is essential in a number of tissues during development. It interacts with Gata1, Tal1, E2A and Lmo2 to form a transcription factor complex regulating late erythroid genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17108004", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 850, "text": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. Importantly, we show that FOG-1 mediates GATA-1 interactions with the MeCP1 complex, thus providing an explanation for the overlapping functions of these two factors in erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 868, "text": "Here we show that Ski interacts with GATA1, a transcription factor essential in erythropoiesis. Using a Ski mutant deficient in GATA1 binding, we show that this Ski-GATA1 interaction is critical for Ski's ability to repress GATA1-mediated transcription and block erythroid differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15542823", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 432, "text": "The zinc finger transcription factor GATA-1, a central mediator of erythroid gene expression, interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12032775", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 1155, "text": "tudies involving point mutants of GATA-1 have shown that a direct physical interaction between GATA-1 and FOG-1 is essential for normal human erythroid and megakaryocyte maturation in vivo. In addition, evidence has emerged that physical interaction between GATA-1 and the myeloid/lymphoid specific factor PU.1, an oncogene implicated in murine erythroleukemia, acts to functionally cross-antagonize one another. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12032775", "endSection": "abstract" } ] }, { "body": "Is farnesoid X receptor (FXR) a nuclear receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23784309", "http://www.ncbi.nlm.nih.gov/pubmed/23688559", "http://www.ncbi.nlm.nih.gov/pubmed/24068255", "http://www.ncbi.nlm.nih.gov/pubmed/23772048", "http://www.ncbi.nlm.nih.gov/pubmed/24037988", "http://www.ncbi.nlm.nih.gov/pubmed/23651738", "http://www.ncbi.nlm.nih.gov/pubmed/23982684", "http://www.ncbi.nlm.nih.gov/pubmed/24177031", "http://www.ncbi.nlm.nih.gov/pubmed/24004079", "http://www.ncbi.nlm.nih.gov/pubmed/24261510", "http://www.ncbi.nlm.nih.gov/pubmed/23720266", "http://www.ncbi.nlm.nih.gov/pubmed/24291500", "http://www.ncbi.nlm.nih.gov/pubmed/24091600", "http://www.ncbi.nlm.nih.gov/pubmed/23609136", "http://www.ncbi.nlm.nih.gov/pubmed/24064762", "http://www.ncbi.nlm.nih.gov/pubmed/23811326", "http://www.ncbi.nlm.nih.gov/pubmed/23861371", "http://www.ncbi.nlm.nih.gov/pubmed/23824184", "http://www.ncbi.nlm.nih.gov/pubmed/24089008", "http://www.ncbi.nlm.nih.gov/pubmed/23680185", "http://www.ncbi.nlm.nih.gov/pubmed/24041925", "http://www.ncbi.nlm.nih.gov/pubmed/24211198" ], "ideal_answer": [ "Yes, farnesoid X receptor (FXR) is a nuclear receptor." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/NR1H4_HUMAN", "http://www.uniprot.org/uniprot/NR1H4_MOUSE", "http://www.uniprot.org/uniprot/NR1H4_BOVIN", "http://www.biosemantics.org/jochem#4250490", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004879", "http://www.uniprot.org/uniprot/NR1H4_RAT", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018160" ], "type": "yesno", "id": "55263a1898daae017c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor superfamily, and functions as a transcription factor regulating the transcription of numerous genes involved in bile acid homeostasis, lipoprotein and glucose metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291500", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 210, "text": " Farnesoid X receptor (FXR) is an ascending target for metabolic and inflammatory diseases. As a nuclear receptor, FXR exhibits many physiological effects in transcription control of several genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24261510", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 269, "text": " FXR is a member of the nuclear receptor superfamily which is also highly expressed in the liver. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24177031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24091600", "endSection": "abstract" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1445, "text": "the nuclear receptor farnesoid X receptor ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24089008", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 784, "text": " farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068255", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 339, "text": "T-\u03b2-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24064762", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 356, "text": " Farnesoid X receptor (FXR), a nuclear receptor (NR) and originally considered as a bile acid-activated transcriptional factor, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041925", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 234, "text": " The nuclear receptor farnesoid X receptor (FXR) plays a major role in the enterohepatic cycling of bile acids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Liver X receptors, LXRs, are ligand-activated transcription factors that belong to the group H nuclear receptor (NR) superfamily. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24004079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The intracellular nuclear receptor farnesoid X receptor and the transmembrane G protein-coupled receptor TGR5 respond to bile acids by activating transcriptional networks and/or signalling cascades.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982684", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 243, "text": "ncluding those of nuclear receptors, primarily farnesoid X receptor (FXR), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23824184", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1383, "text": "ile acids and their cognate nuclear receptor, FXR,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23861371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23811326", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 412, "text": "he activation of the nuclear receptor farnesoid X receptor (FXR\u03b1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23784309", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 322, "text": "bile acid-activated nuclear receptor farnesoid X receptor (FXR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23772048", "endSection": "abstract" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1587, "text": " nuclear receptor signaling, notably by the farnesoid X receptor (FXR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23720266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "FXR (farnesoid X receptor, NRIH4), a nuclear receptor, plays a major role in the control of cholesterol metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688559", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 214, "text": "The role of the nuclear receptor FXR is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23680185", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 39, "text": "nuclear receptor FXR ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23680185", "endSection": "title" }, { "offsetInBeginSection": 27, "offsetInEndSection": 114, "text": "a member of the nuclear receptor superfamily of ligand-activated transcription factors,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23609136", "endSection": "abstract" } ] }, { "body": "What histone variants play a role in the DNA damage reponse?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18296106", "http://www.ncbi.nlm.nih.gov/pubmed/20407219", "http://www.ncbi.nlm.nih.gov/pubmed/11893489", "http://www.ncbi.nlm.nih.gov/pubmed/19234522", "http://www.ncbi.nlm.nih.gov/pubmed/21901086", "http://www.ncbi.nlm.nih.gov/pubmed/16951256", "http://www.ncbi.nlm.nih.gov/pubmed/21383063", "http://www.ncbi.nlm.nih.gov/pubmed/17851762", "http://www.ncbi.nlm.nih.gov/pubmed/19131518", "http://www.ncbi.nlm.nih.gov/pubmed/12202754", "http://www.ncbi.nlm.nih.gov/pubmed/19607843", "http://www.ncbi.nlm.nih.gov/pubmed/21700704", "http://www.ncbi.nlm.nih.gov/pubmed/23777805", "http://www.ncbi.nlm.nih.gov/pubmed/16094454", "http://www.ncbi.nlm.nih.gov/pubmed/23319141", "http://www.ncbi.nlm.nih.gov/pubmed/20703100", "http://www.ncbi.nlm.nih.gov/pubmed/17613284", "http://www.ncbi.nlm.nih.gov/pubmed/23365640", "http://www.ncbi.nlm.nih.gov/pubmed/19896956", "http://www.ncbi.nlm.nih.gov/pubmed/22122340", "http://www.ncbi.nlm.nih.gov/pubmed/22493515", "http://www.ncbi.nlm.nih.gov/pubmed/22331172", "http://www.ncbi.nlm.nih.gov/pubmed/16760674", "http://www.ncbi.nlm.nih.gov/pubmed/22253857" ], "ideal_answer": [ "Mostly H2A.X, but H2A.Z and H1R have also been associated to DNA damage" ], "exact_answer": [ [ "H2A.X" ], [ "H2A.Z" ], [ "H1R" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006974", "http://www.uniprot.org/uniprot/H2BV_BOVIN", "http://www.biosemantics.org/jochem#4278518", "http://www.uniprot.org/uniprot/H2AZ_CHAGB", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004249", "http://www.uniprot.org/uniprot/H2BV_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657" ], "type": "list", "id": "533675ced6d3ac6a34000056", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 333, "text": "H2A.Z is an evolutionarily ancient and highly conserved H2A variant that regulates processes ranging from gene expression to the DNA damage response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22493515", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 746, "text": "activation of DNA damage checkpoints (ataxia telangiectasia mutated (ATM) and H2A histone family, member X (H2AFX (H2AFX)))", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22331172", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 349, "text": "the specialization imparted by histone H2A (H2A.X and H2A.Z) variants to the nucleosome core particle constitutes the earliest response to DNA damage in the cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22253857", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 705, "text": "histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122340", "endSection": "abstract" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1593, "text": "H2A.Z incorporation in the coding regions of genes encoding proteins involved in the regulation of meiosis and genotoxic stress responses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21901086", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 787, "text": " phosphorylation of H2AX, a DNA damage signal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21700704", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 114, "text": "DSB) are generally considered the most critical lesion induced by ionizing radiation (IR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19896956", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 283, "text": "phosphorylated forms of histone H2AX ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19896956", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 710, "text": "H2AX has a complete SQ(E/D)varphi (where varphi denotes a hydrophobic residue) known to be phosphorylated in response to DNA damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19607843", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 774, "text": "H2A.X, plays a very important role in the cellular response to DNA damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19234522", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 201, "text": "H2A.X is an H2A variant present in multicellular organisms that is specifically phosphorylated on the serine in the C-terminal consensus sequence, canonically \"SQEY,\" in response to DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19131518", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 113, "text": "H2AFX) is important in maintaining chromatin structure and genetic stability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17851762", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 78, "text": "Saccharomyces cerevisiae, the linker histone HHO1 is involved in DNA repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613284", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 58, "text": "H1 variant, H1R is involved in DNA damage response", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613284", "endSection": "title" }, { "offsetInBeginSection": 339, "offsetInEndSection": 477, "text": "high levels of histone H2AX phosphorylation and an increased incorporation of the Htz1p histone variant into chromatin surrounding the DSB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951256", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1071, "text": "TRF2 upregulation was more dramatic in drug-resistant cells and occurred before the expression of ATM, gammaH2AX and p53", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16760674", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 305, "text": "DNA double-strand breaks induced by anticancer drugs or irradiation increase TRF2 expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16760674", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 467, "text": "Histone variant H2AX and core histone H2A are phosphorylated in mammals and budding yeast, respectively. We demonstrate the DSB-induced phosphorylation of histone variant H2Av in Drosophila melanogaster", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12202754", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 119, "text": "formation of a double-strand break (DSB) in chromosomal DNA is highly conserved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12202754", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 339, "text": "H2A variants, H2AX and H2AZ. H2AX is phosphorylated on a serine four residues from the carboxyl terminus in response to the introduction of DNA double-strand breaks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11893489", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 649, "text": "In response to IR, ZNF668 knockdown reduces Tip60-H2AX interaction and impairs IR-induced histone H2AX hyperacetylation, thus impairing chromatin relaxation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777805", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1182, "text": "RPA foci formation were reduced in parallel with increasing levels of H2AX phosphorylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23365640", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 182, "text": "H2AX phosphorylation on a C-terminal serine residue to form \"\u03b3-H2AX\" is a critical early event in the chromatin response to chromosomal DNA double strand breaks in eukaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20703100", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1075, "text": "The phosphorylation of the histone variant H2AX (gammaH2AX) is one of the best examples of histone PTMs in response to DNA damage induction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20407219", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 830, "text": "One of the most well-characterized modifications is caused by the formation of DNA double strand breaks (DSBs), resulting in phosphorylation of histone H2AX (the so-called gamma-H2AX) on the chromatin surrounding the DNA lesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18296106", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 867, "text": "H2AX appears to be mainly associated with maintaining the genome integrity by participating in the repair of the double-stranded DNA breaks exogenously introduced by environmental damage (ionizing radiation, chemicals) or in the process of homologous recombination during meiosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16094454", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 645, "text": "The sustained localization of BMI1 to damage sites is dependent on intact ATM and ATR and requires H2AX phosphorylatio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21383063", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1114, "text": "unique functional interactions among various chromatin modifiers, suggesting new regulatory pathways, such as a heterochromatin-specific modulation of DNA damage response involving H2A.X and WICH, both enriched in silent domains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23319141", "endSection": "abstract" } ] }, { "body": "List tele monitoring applications of miniaturised sensors", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18002293", "http://www.ncbi.nlm.nih.gov/pubmed/18002454", "http://www.ncbi.nlm.nih.gov/pubmed/20925563", "http://www.ncbi.nlm.nih.gov/pubmed/21250829", "http://www.ncbi.nlm.nih.gov/pubmed/17272161", "http://www.ncbi.nlm.nih.gov/pubmed/20875149", "http://www.ncbi.nlm.nih.gov/pubmed/21971974", "http://www.ncbi.nlm.nih.gov/pubmed/15718654", "http://www.ncbi.nlm.nih.gov/pubmed/23529100", "http://www.ncbi.nlm.nih.gov/pubmed/19163770", "http://www.ncbi.nlm.nih.gov/pubmed/20597833" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/46062", "o": "Other" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/46062", "o": "Intervention #46062 (Other:Telemonitoring)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/46062", "o": "Telemonitoring" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/39361", "o": "Device" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/39361", "o": "telemonitoring system" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/39361", "o": "Intervention #39361 (Device:telemonitoring system)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/62923", "o": "Device" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/62923", "o": "telemonitoring system" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/62923", "o": "Intervention #62923 (Device:telemonitoring system)" }, { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/52935", "o": "Telemonitored care" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/52935", "o": "Telemonitored care" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/52935", "o": "Intervention #52935 (Behavioral:Telemonitored care)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00435643", "o": "http://data.linkedct.org/resource/intervention/10054" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/10054", "o": "Nurse-led telemonitoring" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00435643", "o": "Trial NCT00435643" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/10054", "o": "Intervention #10054 (Procedure:Nurse-led telemonitoring)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/53160", "o": "Device" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/53160", "o": "Intervention #53160 (Device:HomMed Telemonitoring System)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/53160", "o": "HomMed Telemonitoring System" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/10054", "o": "Procedure" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/10054", "o": "10054" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/53160", "o": "53160" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/39518", "o": "Device" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/39518", "o": "Intervention #39518 (Device:ICD with Telemonitoring)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/39518", "o": "ICD with Telemonitoring" }, { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/39361", "o": "Health Buddy\u00ae telemonitoring system" }, { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/62923", "o": "usual care" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/39518", "o": "39518" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00732069", "o": "http://data.linkedct.org/resource/intervention/10045" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00732069", "o": "Trial NCT00732069" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/10045", "o": "Intervention #10045 (Behavioral:Nurse Behavioral intervention with Home BP Telemonitoring)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/10045", "o": "Nurse Behavioral intervention with Home BP Telemonitoring" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/13986", "o": "Device" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/13986", "o": "Intervention #13986 (Device:Telemonitoring of glucose values using GlucoNet device)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/13986", "o": "Telemonitoring of glucose values using GlucoNet device" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/10049", "o": "10049" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/10049", "o": "Nurse Medication Management with Home BP Telemonitoring" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/10049", "o": "Intervention #10049 (Behavioral:Nurse Medication Management with Home BP Telemonitoring)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00572767", "o": "http://data.linkedct.org/resource/intervention/10047" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/10047", "o": "Intervention #10047 (Behavioral:Nurse Combined intervention with Home BP Telemonitoring)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00572767", "o": "Trial NCT00572767" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/10047", "o": "Nurse Combined intervention with Home BP Telemonitoring" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/10045", "o": "10045" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/10045", "o": "Behavioral" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/10047", "o": "10047" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/13986", "o": "13986" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00700856", "o": "http://data.linkedct.org/resource/intervention/39361" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00700856", "o": "Trial NCT00700856" }, { "p": "http://data.linkedct.org/resource/linkedct/acronym", "s": "http://data.linkedct.org/resource/trials/NCT00700856", "o": "TOSCA IT" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00097656", "o": "http://data.linkedct.org/resource/intervention/39518" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00097656", "o": "Trial NCT00097656" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/10049", "o": "Behavioral" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00214097", "o": "http://data.linkedct.org/resource/intervention/13986" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00214097", "o": "Trial NCT00214097" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00715429", "o": "http://data.linkedct.org/resource/intervention/10049" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00715429", "o": "Trial NCT00715429" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/10047", "o": "Behavioral" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/7206", "o": "7206" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/7206", "o": "In-home telemonitoring of pediatric patients with persistent asthma" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/7206", "o": "Intervention #7206 (Procedure:In-home telemonitoring of pediatric patients with persistent asthma)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/7206", "o": "Procedure" }, { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/39518", "o": "Home Monitoring follow-ups compared to conventional office visit follow-ups of ICDs" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention", "s": "http://data.linkedct.org/resource/trials/NCT00523939", "o": "http://data.linkedct.org/resource/intervention/7206" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00523939", "o": "Trial NCT00523939" }, { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/53160", "o": "The HomMed telemonitoring system allows for patients to monitor their weight, blood pressure, oxygen saturation and symptoms of dyspnoea on a daily basis from their home" }, { "p": "http://data.linkedct.org/resource/linkedct/description", "s": "http://data.linkedct.org/resource/intervention/52936", "o": "Telemonitoring is the use of electronic communications technology by caregivers to monitor patients in their home and promote the engagement of patients in their care." }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/52936", "o": "Intervention #52936 (Behavioral:Telemonitoring)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/52936", "o": "Telemonitoring" } ], "ideal_answer": [ "Home-polysomnography (HPSG)\nBody weight\nBlood pressure control\nHeart failure control\nVital signs - disaster relief, dangerous outdoor sports and adventure monitoring, and antiterrorism activities.\nTelemetric fetal home monitoring system for recording the trans-abdominal fetal heart signal and the uterine contractions\nVital signs - electrocardiograms (ECGs), temperature (T), and oxygen saturation (SaO2) , breath rate\nStep-counting for tele-rehabilitation\nDetection of falls in elderly" ], "exact_answer": [ [ "Sleep monitoring" ], [ "Body weight" ], [ "Blood pressure control" ], [ "Heart failure control" ], [ "vital signs" ], [ "fetal heart signal" ], [ "uterine contractions" ], [ "Electrocardiograms", "ECG" ], [ "Temperature" ], [ "Oxygen saturation", "SaO2" ], [ "breath rate" ], [ "Step-counting" ], [ "Falls detector" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008904" ], "type": "list", "id": "52f895602059c6d71c000040", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 287, "text": "Home-polysomnography (HPSG) has been proposed as a cost-effective alternative for obstructive sleep apnea (OSA) diagnosis. We assessed, in a feasibility study, whether telematic transmission using the Dream\u00ae and Sleepbox\u00ae technologies was associated with low HPSG failure rate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23529100", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 342, "text": " In this study, we monitored remotely self-measured body weight and blood pressure, in parallel with the data automatically transmitted by implantable cardioverter-defibrillators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21971974", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1688, "text": "Body weight, patient activity, and the difference between MHR and RHR are mutually correlated and may reasonably contribute to an algorithm for predicting heart failure deterioration. Blood pressure appears to offer no additional value. As both genesis and symptoms of heart failure exacerbation are non-uniform and complex, the telemonitoring concepts for heart failure patients should employ continuous monitoring of multiple diagnostic parameters, rather than rely on a single parameter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21971974", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 348, "text": "System and can collect users' vital signs with a set of wireless sensors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21250829", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 740, "text": "this terminal is very helpful in special circumstances such as disaster relief, dangerous outdoor sports and adventure monitoring, and antiterrorism activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21250829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "A new, phonocardiography-based telemetric fetal home monitoring system.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20925563", "endSection": "title" }, { "offsetInBeginSection": 207, "offsetInEndSection": 361, "text": "The input element of the system was the home monitor with two sensors for recording the trans-abdominal fetal heart signal and the uterine contractions. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20925563", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1124, "text": "Telemonitoring is currently being used in community-based healthcare, at the scene of medical emergencies, by ambulance services and in hospitals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Mobile telemonitoring for achieving tighter targets of blood pressure control in patients with complicated diabetes: ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20597833", "endSection": "title" }, { "offsetInBeginSection": 449, "offsetInEndSection": 598, "text": "Patients in the intervention arm transmitted weekly blood pressure readings wirelessly, using adapted sensors via mobile phones to a central server. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20597833", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1483, "text": "In patients with diabetes, mobile telemonitoring has potential for delivering intensified care to improve blood pressure control, and its use may be associated with reduced exposure to hyperglycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20597833", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 588, "text": "A new codivilla-spring prosthesis with sensors for telemonitoring / telerehabilitation has been designed and constructed. It provides step counting", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19163770", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 351, "text": "This article is a survey of systems, algorithms and sensors, for the automatic early detection of the fall of elderly persons. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18002293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "We describe a vital sign telemonitor (VST) that acquires, records, displays, and provides readings such as: electrocardiograms (ECGs), temperature (T), and oxygen saturation (SaO2) over the Internet to any site. The design of this system consisted of three parts: sensors, analog signal processing circuits, and a user-friendly graphical user interface (GUI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17272161", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "The paper describes the development of biomedical clothing for ambulatory telemonitoring of human vital parameters. VTAM (Vetement de Tele-Assistance Medicale) presents a T-shirt made from textile with woven wires and incorporating four smooth dry ECG electrodes, a breath rate sensor, a shock/fall detector and two temperature sensors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15718654", "endSection": "abstract" } ] }, { "body": "How are ultraconserved elements called when they form clusters?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "http://www.ncbi.nlm.nih.gov/pubmed/23193254" ], "ideal_answer": [ "Ultraconserved non-coding elements (UCNEs) are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes. Their molecular functions and the reasons for their high degree of conservation remain enigmatic." ], "exact_answer": [ "gene regulatory blocks (GRBs)" ], "type": "factoid", "id": "553c9f96f32186855800000c", "snippets": [ { "offsetInBeginSection": 203, "offsetInEndSection": 532, "text": "We were wondering whether this approach could provide insights about utlraconserved non-coding elements (UCNEs). These elements are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes. Their molecular functions and the reasons for their high degree of conservation remain enigmatic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1084, "text": "This 'winner-takes-all' pattern suggests that UCNEs of a GRB function in a highly cooperative manner. We propose that the multitude of interactions between UCNEs is the reason for their extreme sequence conservation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "UCNEbase--a database of ultraconserved non-coding elements and genomic regulatory blocks", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193254", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 530, "text": "The majority of UCNEs are supposed to be transcriptional regulators of key developmental genes. As most of them occur as clusters near potential target genes, the database is organized along two hierarchical levels: individual UCNEs and ultra-conserved genomic regulatory blocks (UGRBs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193254", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 435, "text": "These elements are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 531, "text": "As most of them occur as clusters near potential target genes, the database is organized along two hierarchical levels: individual UCNEs and ultra-conserved genomic regulatory blocks (UGRBs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193254", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 422, "text": "These elements are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "endSection": "abstract" } ] }, { "body": "What is the basis of the methodology of \"functional class scoring\" (FCS) for the analysis of gene expression data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24565001", "http://www.ncbi.nlm.nih.gov/pubmed/25161229", "http://www.ncbi.nlm.nih.gov/pubmed/16317079", "http://www.ncbi.nlm.nih.gov/pubmed/18990722", "http://www.ncbi.nlm.nih.gov/pubmed/16895928", "http://www.ncbi.nlm.nih.gov/pubmed/16280084", "http://www.ncbi.nlm.nih.gov/pubmed/24497970", "http://www.ncbi.nlm.nih.gov/pubmed/16706726", "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "http://www.ncbi.nlm.nih.gov/pubmed/23934932", "http://www.ncbi.nlm.nih.gov/pubmed/23557376" ], "ideal_answer": [ "The second method, \"functional class scoring\" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step.", "Functional class scoring (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. It consists of a semi-supervised method exploring both the expression pattern and the functional annotation of the genes.", "The second method, \"functional class scoring\" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. " ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063990", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870", "http://amigo.geneontology.org/amigo/term/GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020869" ], "type": "summary", "id": "56f3f2072ac5ed1459000018", "snippets": [ { "offsetInBeginSection": 570, "offsetInEndSection": 782, "text": "The second method, \"functional class scoring\" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 696, "text": "We aimed at examining such discrepancies on the level of apparently affected biologically related groups of genes, e.g. metabolic or signalling pathways. This can be achieved by group testing procedures, e.g. over-representation analysis, functional class scoring (FCS), or global tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16895928", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1111, "text": "They also suggest that functional class scoring methods appear to perform better and more consistently than overrepresentation analysis and distributional score methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16706726", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 736, "text": "With the use of functional class scoring, a semi-supervised method exploring both the expression pattern and the functional annotation of the genes, the Gene Ontology classes were ranked according to the significance of the impact of D3T treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16317079", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 576, "text": "Most of the existing pathway analysis methods focus on either the number of DE genes observed in a given pathway (enrichment analysis methods), or on the correlation between the pathway genes and the class of the samples (functional class scoring methods)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18990722", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 497, "text": " There are three main classes of these methods: over-representation analysis, functional class scoring, and pathway topology based methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24565001", "endSection": "abstract" }, { "offsetInBeginSection": 784, "offsetInEndSection": 980, "text": "Here, we show that all three major categories of pathway analysis methods (enrichment analysis, functional class scoring, and topology-based methods) are severely influenced by crosstalk phenomena", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23934932", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 721, "text": "Proteomics Expansion Pipeline (PEP), Functional Class Scoring (FCS), and Maxlink, in a test scenario of valproic acid (VPA)-treated mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23557376", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1140, "text": "We propose and examine personalized extensions of pathway statistics, overrepresentation analysis and functional class scoring, to generate individualized pathway aberrance score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25161229", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 847, "text": "The comparison of two analytical approaches, based on either Over Representation Analysis or Functional Class Scoring, by a meta-analysis-based approach, led to the retrieval of known information about the biological situation - thus validating the model - but also more importantly to the discovery of the previously unknown implication of the spliceosome, the cellular machinery responsible for mRNA splicing, in the development of metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24497970", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 991, "text": "The second method, \"functional class scoring\" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 801, "text": "The second method, "functional class scoring" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 578, "text": "The first method, "overrepresentation analysis" (ORA), is based on statistically evaluating the fraction of genes in a particular gene ontology class found among the set of genes showing age-related changes in expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Using the gene ontology for microarray data mining: a comparison of methods and application to age effects in human prefrontal cortex", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "title" }, { "offsetInBeginSection": 570, "offsetInEndSection": 783, "text": "The second method, \"functional class scoring\" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 803, "text": "The first method, "overrepresentation analysis" (ORA), is based on statistically evaluating the fraction of genes in a particular gene ontology class found among the set of genes showing age-related changes in expression. The second method, "functional class scoring" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 935, "text": "The second method, "functional class scoring" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. We find that FCS yields more consistent results than ORA, and the results of ORA depended strongly on the gene selection threshold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15176478", "endSection": "abstract" } ] }, { "body": "What is the Timothy syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23690510", "http://www.ncbi.nlm.nih.gov/pubmed/21915623", "http://www.ncbi.nlm.nih.gov/pubmed/17467634", "http://www.ncbi.nlm.nih.gov/pubmed/20301577", "http://www.ncbi.nlm.nih.gov/pubmed/18536931", "http://www.ncbi.nlm.nih.gov/pubmed/22999068", "http://www.ncbi.nlm.nih.gov/pubmed/21910241", "http://www.ncbi.nlm.nih.gov/pubmed/22106044", "http://www.ncbi.nlm.nih.gov/pubmed/23678275", "http://www.ncbi.nlm.nih.gov/pubmed/23313911", "http://www.ncbi.nlm.nih.gov/pubmed/22120178", "http://www.ncbi.nlm.nih.gov/pubmed/21307850", "http://www.ncbi.nlm.nih.gov/pubmed/21700933", "http://www.ncbi.nlm.nih.gov/pubmed/18250309", "http://www.ncbi.nlm.nih.gov/pubmed/21878566", "http://www.ncbi.nlm.nih.gov/pubmed/23580742", "http://www.ncbi.nlm.nih.gov/pubmed/19916019", "http://www.ncbi.nlm.nih.gov/pubmed/24215710", "http://www.ncbi.nlm.nih.gov/pubmed/19001023", "http://www.ncbi.nlm.nih.gov/pubmed/21685391", "http://www.ncbi.nlm.nih.gov/pubmed/22990809", "http://www.ncbi.nlm.nih.gov/pubmed/23299782" ], "ideal_answer": [ "Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of the same gene. Cardiac findings include a rate-corrected QT interval of between 480 ms and 700 ms and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include flat nasal bridge, low-set ears, thin upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0060173" ], "type": "summary", "id": "53173fc5b166e2b806000006", "snippets": [ { "offsetInBeginSection": 133, "offsetInEndSection": 284, "text": "A point mutation in the gene encoding Ca(V)1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23313911", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 577, "text": "o circumvent this issue, we have developed a method using human-induced pluripotent stem cells to generate cardiomyocytes from individuals with Timothy syndrome (TS), a genetic disorder characterized by QT prolongation, ventricular tachycardia, and autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23299782", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 472, "text": "Two de novo point mutations of Ca(v)1.2 glycine residues, G406R and G402S, cause a rare multisystem disorder called Timothy syndrome (TS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22999068", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 693, "text": "Here, we discuss recent work on the mechanisms by which Ca(v)1.2 channels bearing TS mutations display slowed inactivation that leads to increased Ca(2+) influx, prolonging the cardiac AP and promoting lethal arrhythmias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22999068", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 669, "text": "Timothy syndrome is a human genetic disorder due to mutations in the Ca(V)1.2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990809", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 390, "text": "Timothy syndrome (TS) is a disease caused by a gain-of-function mutation in the CaV1.2 channel (CaV1.2-TS) that decreases inactivation of the channel, which increases Ca(2+) influx, prolongs APs, and causes lethal arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24215710", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 414, "text": "Recent reports suggest that parental mosaicism is involved in the heritability of type 1 Timothy syndrome (TS1), an extremely rare and life-threatening multisystem disorder characterized by severe QT interval prolongation, syndactyly, and several other complications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23690510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Timothy syndrome, long QT syndrome type 8, is highly malignant with ventricular tachyarrhythmia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23678275", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 144, "text": "Timothy syndrome (TS) is a rare long-QT syndrome caused by CACNA1C mutations G406R in exon 8A (TS1) and G402S/G406R in exon 8 (TS2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580742", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 323, "text": "Timothy syndrome is caused by a missense mutation in the L-type calcium channel Ca(v)1.2 that is associated with developmental delay and autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22106044", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Timothy syndrome (TS) is an autosomal dominant condition with the constellation of features including prolonged QT interval, hand and foot abnormalities, and mental retardation or autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22106044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Timothy syndrome type 1 (TS-1) is a rare disorder that affects multiple organ systems and has a high incidence of sudden death due to profound QT prolongation and resultant ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21910241", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 554, "text": "In some rare cases, such as Timothy syndrome (TS), a specific mutation in a single gene can be sufficient to generate autism or ASD in most patients, potentially offering insights into the etiology of autism in general. Both variants of TS (the milder TS1 and the more severe TS2) arise from missense mutations in alternatively spliced exons that cause the same G406R replacement in the Ca(V)1.2 L-type calcium channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21878566", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 306, "text": "A gain-of-function G406R mutation in a cytoplasmic loop of Ca(V)1.2 channels causes long QT syndrome 8 (LQT8), a disease also known as Timothy syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21700933", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 363, "text": "A missense mutation in the L-type calcium channel Ca(V)1.2 leads to LQTS in patients with Timothy syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21307850", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 1068, "text": "Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of the same gene. Cardiac findings include a rate-corrected QT interval of between 480 ms and 700 ms and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include flat nasal bridge, low-set ears, thin upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301577", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 260, "text": "The gain-of-function mutations were found at two mutually exclusive exons in patients with Timothy syndrome (TS). These patients exhibit prolonged QT interval and lethal cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19916019", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 611, "text": "TS patients also suffer from multi-organ dysfunction that includes neurological disorder such as autism and mental retardation reflecting the wide tissue distribution of CaV1.2 channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19916019", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 839, "text": "Unexpectedly, TS patients may develop recurrent infections and bronchitis that suggests a role of CaV1.2 channel in the immune system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19916019", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 396, "text": "Timothy syndrome (TS) is a disease of excessive cellular Ca(2+) entry and life-threatening arrhythmias caused by a mutation in the primary cardiac L-type Ca(2+) channel (Ca(V)1.2). The TS mutation causes loss of normal voltage-dependent inactivation of Ca(V)1.2 current (I(Ca)). During cellular Ca(2+) overload, the calmodulin-dependent protein kinase II (CaMKII) causes arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19001023", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 336, "text": "Timothy syndrome is a multisystem disorder associated with the mutation of a Gly residue (G402 or G406) in the Ca(v)1.2 Ca(2+) channel. G406 is localized at the end of the IS6 segment and just before the intracellular I-II loop, which is important for the regulation of channel inactivation and the binding of the Ca(v)beta subunit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18536931", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 765, "text": "Inactivation of Ca2+ channel activity is perturbed in a rare yet devastating disorder known as Timothy syndrome (TS), whose features include autism or autism spectrum disorder along with severe cardiac arrhythmia and developmental abnormalities. Most cases of TS arise from a sporadic single nucleotide change that generates a mutation (G406R) in the pore-forming subunit of the L-type Ca2+ channel Ca(V)1.2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250309", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 257, "text": "Timothy syndrome is a multisystem disorder associated with QT interval prolongation and ventricular cardiac arrhythmias. The syndrome has been linked to mutations in Ca(V)1.2 resulting in gain of function of the L-type calcium current (I(Ca,L)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17467634", "endSection": "abstract" } ] }, { "body": "Which disease has been associated to a disruptive ALX1 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20451171", "http://www.ncbi.nlm.nih.gov/pubmed/20627960", "http://www.ncbi.nlm.nih.gov/pubmed/8673125", "http://www.ncbi.nlm.nih.gov/pubmed/15728667", "http://www.ncbi.nlm.nih.gov/pubmed/12390248", "http://www.ncbi.nlm.nih.gov/pubmed/24376213", "http://www.ncbi.nlm.nih.gov/pubmed/12559496", "http://www.ncbi.nlm.nih.gov/pubmed/25686609", "http://www.ncbi.nlm.nih.gov/pubmed/19598128" ], "ideal_answer": [ "Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia." ], "exact_answer": [ "frontonasal dysplasia" ], "type": "factoid", "id": "56cf36263975bb303a000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20451171", "endSection": "title" }, { "offsetInBeginSection": 650, "offsetInEndSection": 882, "text": "In the second family we identified a homozygous donor-splice-site mutation (c.531+1G>A) in the ALX1 gene, providing evidence that complete loss of function of ALX1 protein causes severe disruption of early craniofacial development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20451171", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1070, "text": "expression of Alx1, an effector of scapula blade patterning, is absent in all compound mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20627960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Mutations in each of the transcriptional co-activator genes - CBP, p300, Cited2, Cart1 and Carm1 - result in neural tube defects in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19598128", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1168, "text": "Scapular truncation in triple mutants of Tbx15, Alx4 and Cart1 indicates essential functions for Alx4 and Cart1 in the anterior part of the scapula", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15728667", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 854, "text": " Ectopic expression of Cart1 in transgenic mice does not disturb development, whereas expression of a Cart1 form from which the aristaless domain has been deleted results in severe cranial and vertebral malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12559496", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 502, "text": "Cart1, is essential for correct morphogenesis of the limbs and cranium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12559496", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 196, "text": "Cart1 encodes the paired-like homeodomain in the central portion of the gene, and plays a crucial role in the developmental lineage of bone and cartilage, especially in head formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12390248", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 382, "text": "we show that Cart1-homozygous mutant mice are born alive with acrania and meroanencephaly but die soon after birth-a phenotype that strikingly resembles a corresponding human syndrome caused by a neural tube closure defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8673125", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 649, "text": " 240\u00a0kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25686609", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 492, "text": "ALX3, ALX4, and ALX1, which have been related with distinct phenotypes named FND1, FND2, and FND3 respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24376213", "endSection": "abstract" } ] }, { "body": "How many selenoproteins are encoded in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22943432", "http://www.ncbi.nlm.nih.gov/pubmed/18174224", "http://www.ncbi.nlm.nih.gov/pubmed/12775843", "http://www.ncbi.nlm.nih.gov/pubmed/15843685" ], "ideal_answer": [ "25. 15kDa, DI1, DI2, DI3, GPx1, GPx2, GPx3, GPx4, GPx6, SelH, SelI, SelK, SelM, SelN, SelO, SelP, SelR, SelS, SPS2, SelT, TR1, TR2, TR3, SelV and SelW." ], "exact_answer": [ "25" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051140" ], "type": "factoid", "id": "517170c48ed59a060a00000d", "snippets": [ { "offsetInBeginSection": 448, "offsetInEndSection": 503, "text": "The human selenoproteome consists of 25 selenoproteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12775843", "endSection": "sections.0" } ] }, { "body": "In which process Src, Cortactin and MT1-MMP are playing an essential role?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16540652", "http://www.ncbi.nlm.nih.gov/pubmed/22039045", "http://www.ncbi.nlm.nih.gov/pubmed/20937825", "http://www.ncbi.nlm.nih.gov/pubmed/23417847", "http://www.ncbi.nlm.nih.gov/pubmed/17446433", "http://www.ncbi.nlm.nih.gov/pubmed/19704022" ], "ideal_answer": [ "Src was shown to be required for invadopodia formation and function, whereas Cortactin was found to regulate cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. Finally, membrane type 1 matrix metalloproteinase (MT1-MMP) was demostrated as the key invadopodial enzyme responsible for gelatin matrix degradation in cancer cells." ], "exact_answer": [ "Src, Cortactin and MT1-MMP play an essential role in the formation and function of invadopodia." ], "concepts": [ "http://www.uniprot.org/uniprot/SRC_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019061", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053511", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051356", "http://www.uniprot.org/uniprot/SRC8_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016391", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020782", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053504", "http://www.uniprot.org/uniprot/MMP14_HUMAN" ], "type": "factoid", "id": "534eb34b288f4dae47000002", "snippets": [ { "offsetInBeginSection": 730, "offsetInEndSection": 1021, "text": "Further investigation into the underlying molecular mechanisms revealed that the levels of key modulators of invadopodium maturation, including c-Src kinase, cortactin, and membrane type 1-matrix metalloproteinase (MT1-MMP) decreased when cells were treated with 6-shogaol or pterostilbene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23417847", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1369, "text": "These data suggest that the repression of these factors might affect the maturation of invadopodia, inhibiting the metastasis of MDA-MB-231 cells. In conclusion, the present study demonstrates for the first time that 6-shogaol and pterostilbene can inhibit invadopodium formation and MMP activity in highly invasive breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23417847", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 1178, "text": "EcTI was shown to decrease the expression and disrupt the cellular organization of molecules involved in the formation and maturation of invadopodia, such as integrin \u03b21, cortactin, neuronal Wiskott-Aldrich syndrome protein, membrane type 1 metalloprotease, and metalloproteinase-2. Moreover, gastric cancer cells treated with EcTI presented a significant decrease in intracellular phosphorylated Src and focal adhesion kinase, integrin-dependent cell signaling components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22039045", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 850, "text": "We show that Abl kinases are activated downstream of the chemokine receptor, CXCR4, and are required for cancer cell invasion and matrix degradation induced by SDF1\u03b1, serum growth factors, and activated Src kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937825", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1028, "text": "Moreover, Abl kinases are readily detected at invadopodia assembly sites and their inhibition prevents the assembly of actin and cortactin into organized invadopodia structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937825", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1198, "text": "We show that active Abl kinases form complexes with membrane type-1 matrix metalloproteinase (MT1-MMP), a critical invadopodia component required for matrix degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937825", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 455, "text": "We have dissected the stages of invadopodium assembly and maturation and show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, cortactin phosphorylation was found to regulate cofilin and Arp2/3 complex-dependent actin polymerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704022", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 844, "text": "Cortactin phosphorylation is required to release this inhibition so cofilin can sever actin filaments to create barbed ends at invadopodia to support Arp2/3-dependent actin polymerization. After barbed end formation, cortactin is dephosphorylated, which blocks cofilin severing activity thereby stabilizing invadopodia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704022", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 500, "text": "In this report we show that the expression of activated versions of Src, Cdc42 and Rac1, or a kinase-dead but open form of the p21-activated kinase (PAK1), induces primary rat aorta VSMCs to form extracellular matrix-degrading actin-rich protrusions that are morphologically similar to the invadopodia formed by highly invasive tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17446433", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 754, "text": "The matrix-degrading structures are enriched in known markers for invadopodia, including cortactin and tyrosine-phosphorylated cortactin and contain the matrix metalloproteinases MMP-9 and MT1-MMP and the urokinase plasminogen activator receptor (uPAR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17446433", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1093, "text": "Invadopodia formation by Src was dependent on Cdc42, Rac, and ERK, but not on p38 MAPK. Invadopodia formation induced by kinase-dead PAK1 required Src and ERK activity and a direct interaction with the exchange factor PIX.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17446433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540652", "endSection": "title" }, { "offsetInBeginSection": 532, "offsetInEndSection": 864, "text": "Small interfering RNA (siRNA) inhibition established that organization of invadopodia structure requires cortactin, whereas protease inhibitor studies identified membrane type 1 matrix metalloproteinase (MT1-MMP) as the key invadopodial enzyme responsible for gelatin matrix degradation in the breast carcinoma cell line MDA-MB-231.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540652", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1020, "text": "The inhibition of invadopodial structure assembly by cortactin depletion resulted in a block of matrix degradation due to failure of invadopodia formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540652", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1239, "text": "Either protease inhibition or MT1-MMP siRNA depletion moderately decreased the formation of invadopodial structures that were identified as actin-cortactin accumulations at the ventral cell membrane adherent to matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540652", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1807, "text": "Examination of cells at different time points as well as live-cell imaging revealed four distinct invadopodial stages: membrane cortactin aggregation at membranes adherent to matrix, MT1-MMP accumulation at the region of cortactin accumulation, matrix degradation at the invadopodia region, and subsequent cortactin dissociation from the area of continued MT1-MMP accumulation associated with foci of degraded matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540652", "endSection": "abstract" } ] }, { "body": "In which yeast chromosome does the rDNA cluster reside?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8371105", "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "http://www.ncbi.nlm.nih.gov/pubmed/24333410", "http://www.ncbi.nlm.nih.gov/pubmed/8175878", "http://www.ncbi.nlm.nih.gov/pubmed/9169867" ], "ideal_answer": [ "Chromosome XII context is important for rDNA function in yeast", "The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit.", "Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast. The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit. However, in cells arrested in late mitosis (M) by a cdc15 mutation, the unique DNA appeared decondensed while the repetitive rDNA region appeared condensed, suggesting that the condensation state of separate regions of the genome may be regulated differently. Finally our FISH method provides a new tool to analyze centromeres, telomeres, and gene expression in budding yeast." ], "exact_answer": [ "chromosome XII", "chromosome 12" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012441", "http://amigo.geneontology.org/amigo/term/GO:0005694" ], "type": "factoid", "id": "5710e131a5ed216440000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Chromosome XII context is important for rDNA function in yeast", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 664, "text": "To explore the biological significance of this specific chromosomal context, chromosome XII was split at both sides of the rDNA cluster and strains harboring deleted variants of chromosome XII consisting of 450 kb, 1500 kb (rDNA cluster only) and 610 kb were created. In the strain harboring the 1500 kb variant of chromosome XII consisting solely of rDNA, the size of the rDNA cluster was found to decrease as a result of a decrease in rDNA copy number", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1456, "text": "These observations suggest that the context of chromosome XII plays an important role in maintaining a constant rDNA copy number and in physiological processes related to rDNA function in S.cerevisiae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1253, "text": "Notably, strains harboring the 450 kb chromosome XII variant and/or the 1500 kb variant consisting solely of rDNA had shorter life spans than wild type and also accumulated extrachromosomal rDNA circles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 720, "text": "Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8175878", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 879, "text": "Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8175878", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 744, "text": "To explore the biological significance of this specific chromosomal context, chromosome XII was split at both sides of the rDNA cluster and strains harboring deleted variants of chromosome XII consisting of 450 kb, 1500 kb (rDNA cluster only) and 610 kb were created.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 849, "text": "In the strain harboring the 1500 kb variant of chromosome XII consisting solely of rDNA, the size of the rDNA cluster was found to decrease as a result of a decrease in rDNA copy number.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 340, "text": "Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9169867", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 754, "text": "We studied the largest yeast chromosome XII, which contains the rDNA locus, and we investigated its instability using cell cycle checkpoint-, DNA damage- and antioxidative defence-deficient, and lifespan-deregulated yeast mutant strains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24333410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Chromosome XII context is important for rDNA function in yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "title" }, { "offsetInBeginSection": 559, "offsetInEndSection": 721, "text": "Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8175878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Clonal size-variation of rDNA cluster region on chromosome XII of Saccharomyces cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8371105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Using pulsed-field gel electrophoresis (PFGE), we have demonstrated clonal variation in the size of chromosome XII in a diploid strain of Saccharomyces cerevisiae X2180-2D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8371105", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 276, "text": "The sizes of the two chromosome XII homologues were very different: 2600 (L-type) and 1450 kb (S-type).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8371105", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 898, "text": "The size variation was shown to be derived from size changes in the rDNA cluster region, which is present in chromosome XII, by digesting the chromosome with XhoI, whose cutting site is not present in a rDNA repeat unit, and hybridizing to rDNA probes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8371105", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 220, "text": "Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9169867", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 721, "text": "Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8175878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Chromosome XII context is important for rDNA function in yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738130", "endSection": "title" } ] }, { "body": "Which is the underlying mechanism for exon skipping used to treat Duchenne muscular dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19140108", "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "http://www.ncbi.nlm.nih.gov/pubmed/23521559", "http://www.ncbi.nlm.nih.gov/pubmed/20150322", "http://www.ncbi.nlm.nih.gov/pubmed/24380394", "http://www.ncbi.nlm.nih.gov/pubmed/17612397" ], "ideal_answer": [ "Antisense-mediated exon skipping therapy is a promising therapeutic approach that uses short DNA-like molecules called antisense oligonucleotides (AOs) to skip over/splice out the mutated part of the gene to produce a shortened but functional dystrophin protein. Many Duchenne Muscular Dystrophy patients need exon skipping of multiple exons in order to restore the reading frame, depending on how many base pairs the mutated exon(s) and adjacent exons have.", "Antisense-mediated exon skipping therapy is a promising therapeutic approach that uses short DNA-like molecules called antisense oligonucleotides (AOs) to skip over/splice out the mutated part of the gene to produce a shortened but functional dystrophin protein ", "Antisense-mediated exon skipping therapy is a promising therapeutic approach that uses short DNA-like molecules called antisense oligonucleotides (AOs) to skip over/splice out the mutated part of the gene to produce a shortened but functional dystrophin protein", "Antisense oligonucleotides (AONs) that bind to complementary sequences of the dystrophin pre-mRNA to induce skipping of the targeted exon by modulating pre-mRNA splicing are promising therapeutic agents for DMD. In addition, multiple exon skipping could be used to select deletions that optimize the functionality of the truncated dystrophin protein. Theoretically, multiple exon skipping could be used to treat approximately 90%, 80%, and 98% of DMD patients with deletion, duplication, and nonsense mutations, respectively. One major challenge has been its limited applicability." ], "type": "summary", "id": "5713394af9287de436000001", "snippets": [ { "offsetInBeginSection": 201, "offsetInEndSection": 462, "text": "Antisense-mediated exon skipping therapy is a promising therapeutic approach that uses short DNA-like molecules called antisense oligonucleotides (AOs) to skip over/splice out the mutated part of the gene to produce a shortened but functional dystrophin protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24380394", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 942, "text": "many DMD patients need exon skipping of multiple exons in order to restore the reading frame, depending on how many base pairs the mutated exon(s) and adjacent exons have. Theoretically, multiple exon skipping could be used to treat approximately 90%, 80%, and 98% of DMD patients with deletion, duplication, and nonsense mutations, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24380394", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 659, "text": "Antisense oligonucleotides (AONs) that bind to complementary sequences of the dystrophin pre-mRNA to induce skipping of the targeted exon by modulating pre-mRNA splicing are promising therapeutic agents for DMD. Such AONs can restore the open reading frame of the DMD gene and produce internally deleted, yet partially functional dystrophin protein isoforms in skeletal muscle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23521559", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1602, "text": "Of all novel molecular interventions currently being investigated for Duchenne muscular dystrophy, perhaps the most promising method aiming to restore dystrophin expression to diseased cells is known as 'exon skipping' or splice-modulation, whereby antisense oligonucleotides eliminate the deleterious effects of DMD mutations by modulating dystrophin pre-messenger RNA splicing, such that functional dystrophin protein is produced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20150322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 336, "text": "Using antisense oligonucleotides (AONs), the disrupted DMD reading frame is restored, allowing generation of partially functional dystrophin and conversion of a severe Duchenne into a milder Becker muscular dystrophy phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19140108", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 296, "text": "Using antisense oligonucleotides (AONs) targeting specific exons the DMD reading frame is restored and partially functional dystrophins are produced. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17612397", "endSection": "abstract" } ] }, { "body": "What is the advantage of using long nano columns in proteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20382391", "http://www.ncbi.nlm.nih.gov/pubmed/22021278", "http://www.ncbi.nlm.nih.gov/pubmed/21751368", "http://www.ncbi.nlm.nih.gov/pubmed/22728655", "http://www.ncbi.nlm.nih.gov/pubmed/15058572", "http://www.ncbi.nlm.nih.gov/pubmed/23210603", "http://www.ncbi.nlm.nih.gov/pubmed/22265351" ], "ideal_answer": [ "The longer the columns, the longer gradients are applied and finally more proteins (increased peak capacity) are identified in a complex proteomic experiment" ], "type": "summary", "id": "515b1eccd24251bc050000af", "snippets": [ { "offsetInBeginSection": 1146, "offsetInEndSection": 1325, "text": "Our results indicate that this simplified one-shot proteomics approach with long monolithic columns is advantageous for rapid, deep, sensitive, and reproducible proteome analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23210603", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Rapid and deep profiling of human induced pluripotent stem cell proteome by one-shot NanoLC-MS/MS analysis with meter-scale monolithic silica columns.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23210603", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Here, we describe an in-house built ultra-high pressure liquid chromatography (UHPLC) system, with little complexity in design and high separation power combined with convenience in operation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728655", "endSection": "sections.0" }, { "offsetInBeginSection": 503, "offsetInEndSection": 772, "text": "With the longest gradient we identified over 4500 protein groups and more than 26,000 unique peptides from 1 \u03bcg of a human cancer cell lysate in a single run using an Orbitrap Velos - a level of performance often seen solely using multidimensional separation strategies", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728655", "endSection": "sections.0" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1228, "text": "Our data demonstrate that the combination of UHPLC with high resolution mass spectrometry at increased sequencing speeds enables extensive proteome analysis in single runs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728655", "endSection": "sections.0" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1715, "text": "The experimental results showed that the numbers of identified peptides and proteins were maximized and reached a plateau with a gradient time of several tens of hours, which indicated that our model to optimize one dimensional HPLC conditions with a long column could be verified and useful.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22265351", "endSection": "sections.0" }, { "offsetInBeginSection": 257, "offsetInEndSection": 472, "text": "In this study, we combined well-approved techniques, namely elevated chromatographic temperatures, long RP columns and the multidimensional protein identification technology MudPIT to achieve high proteome coverage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21751368", "endSection": "sections.0" }, { "offsetInBeginSection": 717, "offsetInEndSection": 810, "text": "Also, a high identification rate for the challenging integral membrane proteins was achieved.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21751368", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "High-efficiency liquid chromatography-mass spectrometry separations with 50 mm, 250 mm, and 1 m long polymer-based monolithic capillary columns for the characterization of complex proteolytic digests.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382391", "endSection": "title" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1288, "text": "For the analysis of a proteolytic digest of Escherichia coli proteins a monolithic capillary column of 1m in length was used, yielding a peak capacity of 1038 when applying a 600 min gradient.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382391", "endSection": "sections.0" }, { "offsetInBeginSection": 334, "offsetInEndSection": 561, "text": ". It was found that very high resolutions are attainable at long gradient times with long columns. The resolution continuously became higher as the gradient time and the column length became longer except in some special cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15058572", "endSection": "sections.0" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1070, "text": ", such separations should be advantageous when very high resolutions are required like in proteomics research.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15058572", "endSection": "sections.0" } ] }, { "body": "During which stage of the cell cycle is cohesin deposited on the yeast genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11069892", "http://www.ncbi.nlm.nih.gov/pubmed/17670945", "http://www.ncbi.nlm.nih.gov/pubmed/15870297", "http://www.ncbi.nlm.nih.gov/pubmed/24778232", "http://www.ncbi.nlm.nih.gov/pubmed/18178375", "http://www.ncbi.nlm.nih.gov/pubmed/11081625", "http://www.ncbi.nlm.nih.gov/pubmed/15137940", "http://www.ncbi.nlm.nih.gov/pubmed/15309048", "http://www.ncbi.nlm.nih.gov/pubmed/18079700", "http://www.ncbi.nlm.nih.gov/pubmed/9990856", "http://www.ncbi.nlm.nih.gov/pubmed/22677545" ], "ideal_answer": [ "In the budding yeast, cohesin is loaded onto the chromosome during the late G1 phase, establishes sister chromatid cohesion concomitant with DNA replication, and dissociates by the telophase.", "In the budding yeast, cohesin is loaded onto the chromosome during the late G1 phase, establishes sister chromatid cohesion concomitant with DNA replication, and dissociates by the telophase. ", "Cohesin association with G1 chromosomes requires continued activity of the cohesin loader Mis4/Ssl3, suggesting that repeated loading cycles maintain cohesin binding. In mammalian cells, cohesin binding to chromatin is dynamic in G1, but becomes stabilized during S-phase. Instead, we find that cohesin stability increases at the time of S-phase in a reaction that can be uncoupled from DNA replication. Budding yeast Scc1p/Mcd1p, an essential subunit, is cleaved and dissociates from chromosomes in anaphase, leading to sister chromatid separation." ], "exact_answer": [ "S-phase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002453", "http://amigo.geneontology.org/amigo/term/GO:0007049" ], "type": "factoid", "id": "56e2acfe51531f7e33000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "In the budding yeast, cohesin is loaded onto the chromosome during the late G1 phase, establishes sister chromatid cohesion concomitant with DNA replication, and dissociates by the telophase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18178375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Sister chromatid cohesion is mediated by cohesin, but the process of cohesion establishment during S-phase is still enigmatic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18079700", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1022, "text": "Instead, we find that cohesin stability increases at the time of S-phase in a reaction that can be uncoupled from DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18079700", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 607, "text": "By using \"single-copy\" derivatives of the 2-microm plasmid, we demonstrate that recruitment of cohesin at STB during S phase indeed translates into cohesion between plasmid molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17670945", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 992, "text": "In cells recovering from nocodazole-induced spindle depolymerization and G(2)/M arrest, cohesin-STB association can be established coincident with spindle restoration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15870297", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1076, "text": "This postreplication recruitment of cohesin is not functional in equipartitioning. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15870297", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 325, "text": "We have used chromatin immunoprecipitation coupled with microarray analysis (ChIP chip) to produce a genome-wide description of cohesin binding to meiotic and mitotic chromosomes of Saccharomyces cerevisiae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15309048", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 623, "text": "Cohesin sites are highly conserved in meiosis and mitosis, suggesting that chromosomes share a common underlying structure during different developmental programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15309048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Cohesin complex acts in the formation and maintenance of sister chromatid cohesion during and after S phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11069892", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 561, "text": " Proteolytic cleavage of cohesin's Sccl subunit at the metaphase to anaphase transition is essential for sister chromatid separation and depends on a conserved protein called separin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11081625", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 705, "text": "Four of these proteins, Scc1p, Scc3p, Smc1p, and Smc3p, are subunits of a 'Cohesin' complex that binds chromosomes from late G1 until the onset of anaphase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9990856", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1018, "text": "It is necessary for the establishment of cohesion during DNA replication but not for its maintenance during G2 and M phases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9990856", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 501, "text": "Here, we show that cohesin destruction in metaphase is sufficient for segregation of much of the budding yeast genome, but not of the long arm of chromosome XII that contains the rDNA repeats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15137940", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1668, "text": "In this review, we have discussed the life cycle of cohesin during both mitotic and meiotic cell divisions including the structure and architecture of cohesin complex, relevance of cohesin associated proteins, mechanism of cohesin loading onto the chromatin, cohesion establishment and the mechanism of cohesin disassembly during anaphase to separate the sister chromatids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22677545", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 755, "text": "Cohesin association with G1 chromosomes requires continued activity of the cohesin loader Mis4/Ssl3, suggesting that repeated loading cycles maintain cohesin binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18079700", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Cdc14 phosphatase induces rDNA condensation and resolves cohesin-independent cohesion during budding yeast anaphase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15137940", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 658, "text": "Cohesins are deposited by a conserved heterodimeric loading complex composed of the Scc2 and Scc4 proteins in Saccharomyces cerevisiae, but how the Scc2/Scc4 deposition complex regulates the spatiotemporal association of cohesin with chromosomes is not understood. We examined Scc2 chromatin association during the cell division cycle and found that the affinity of Scc2 for chromatin increases biphasically during the cell cycle, increasing first transiently in late G1 phase and then again later in G2/M.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24778232", "endSection": "abstract" } ] }, { "body": "Which is the neurodevelopmental disorder associated to mutations in the X- linked gene mecp2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22670134", "http://www.ncbi.nlm.nih.gov/pubmed/11738860", "http://www.ncbi.nlm.nih.gov/pubmed/11269512", "http://www.ncbi.nlm.nih.gov/pubmed/11402105", "http://www.ncbi.nlm.nih.gov/pubmed/12111643", "http://www.ncbi.nlm.nih.gov/pubmed/19495527", "http://www.ncbi.nlm.nih.gov/pubmed/11960578", "http://www.ncbi.nlm.nih.gov/pubmed/18332345", "http://www.ncbi.nlm.nih.gov/pubmed/23449173", "http://www.ncbi.nlm.nih.gov/pubmed/21982064", "http://www.ncbi.nlm.nih.gov/pubmed/22982301", "http://www.ncbi.nlm.nih.gov/pubmed/10577905", "http://www.ncbi.nlm.nih.gov/pubmed/18337588", "http://www.ncbi.nlm.nih.gov/pubmed/10767337", "http://www.ncbi.nlm.nih.gov/pubmed/17089071", "http://www.ncbi.nlm.nih.gov/pubmed/11462237", "http://www.ncbi.nlm.nih.gov/pubmed/11524741", "http://www.ncbi.nlm.nih.gov/pubmed/17387578", "http://www.ncbi.nlm.nih.gov/pubmed/11055898", "http://www.ncbi.nlm.nih.gov/pubmed/11313756" ], "ideal_answer": [ "The neurodevelopmental disorder named Rett syndrome, originally termed as cerebroatrophic hyperammonemia. Although most exclusively affects females, has also been found in male patients." ], "exact_answer": [ "Rett syndrome" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051783", "http://www.uniprot.org/uniprot/MECP2_MACFA" ], "type": "factoid", "id": "517818508ed59a060a000035", "snippets": [ { "offsetInBeginSection": 553, "offsetInEndSection": 650, "text": "Rett syndrome is caused by mutations in the gene coding for methyl CpG-binding protein 2 (MeCP2).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23449173", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "Rett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22670134", "endSection": "sections.0" }, { "offsetInBeginSection": 189, "offsetInEndSection": 541, "text": "Recently, this syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of still unknown target genes. Here we report a detailed mutational analysis of 62 patients from UK and Italian archives, representing the first comparative study among different populations and one of the largest number of cases so far analyzed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11269512", "endSection": "sections.0" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1219, "text": "Out of the 365 cases, 315 had MECP2 gene mutations and 3 had de novo CDKL5 gene mutations. No patients had FOXG1 mutation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982301", "endSection": "sections.0" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1284, "text": "Mutations were detected in \u2248 70% of classic and \u2248 21% of variant RTT, respectively. Amongst MR cases, 2.1% carried MECP2 mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21982064", "endSection": "sections.0" }, { "offsetInBeginSection": 692, "offsetInEndSection": 775, "text": "Mutations in the MECP2 gene were detected in 13 of the 20 (65 percent) RS patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19495527", "endSection": "sections.0" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1351, "text": "This multicenter investigation into the phenotypic correlates of MECP2 mutations in Rett syndrome has provided a greater depth of understanding than hitherto available about the specific phenotypic characteristics associated with commonly occurring mutations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18332345", "endSection": "sections.0" }, { "offsetInBeginSection": 821, "offsetInEndSection": 923, "text": "Mutation screening revealed 31 different mutations in 68 patients and 12 non-pathogenic polymorphisms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387578", "endSection": "sections.0" }, { "offsetInBeginSection": 151, "offsetInEndSection": 374, "text": "In this study, the MECP2 sequences in 121 unrelated Chinese patients with classical or atypical RTT were screened for deletions and mutations. In all, we identified 45 different MECP2 mutations in 102 of these RTT patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17089071", "endSection": "sections.0" }, { "offsetInBeginSection": 387, "offsetInEndSection": 429, "text": "Mutations in MECP2 were found in about 55%", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12111643", "endSection": "sections.0" }, { "offsetInBeginSection": 206, "offsetInEndSection": 368, "text": "We identified mutations in the MECP2 gene and documented the clinical manifestations in 65 Rett syndrome patients to characterize the genotype-phenotype spectrum.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11960578", "endSection": "sections.0" }, { "offsetInBeginSection": 177, "offsetInEndSection": 506, "text": "We searched for mutations by sequencing the MECP2 coding region in 45 sporadic cases (35 with classic RTT, eight with variant forms and two males) and in seven families with two or more affected females. Following our previous report of mutations in two families and eight sporadic cases, we here present 18 additional mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11738860", "endSection": "sections.0" }, { "offsetInBeginSection": 148, "offsetInEndSection": 433, "text": "The responsible gene, encoding methyl-CpG binding protein 2 (MeCP2), was recently discovered. Here we explore the spectrum of phenotypes resulting from MECP2 mutations. Both nonsense (R168X and R255X) and missense (R106W and R306C) mutations have been found, with multiple recurrences.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10577905", "endSection": "sections.0" }, { "offsetInBeginSection": 566, "offsetInEndSection": 747, "text": "Mutations were identified in 44/55 (80%) unrelated classical sporadic and familial RTT patients, but only 1/5 (20%) sporadic cases with suggestive but non-diagnostic features of RTT", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10767337", "endSection": "sections.0" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1244, "text": "Collectively, we tested 228 unrelated female patients with a diagnosis of possible (209) or classic (19) RTT and found MECP2 mutations in 83 (40%) of 209 and 16 (84%) of 19 of the patients, respectively. Thirty-two different mutations were identified (8 missense, 9 nonsense, 1 splice site, and 14 frameshifts), of which 12 are novel and 9 recurrent in unrelated patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11055898", "endSection": "sections.0" }, { "offsetInBeginSection": 405, "offsetInEndSection": 513, "text": "Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11524741", "endSection": "sections.0" }, { "offsetInBeginSection": 855, "offsetInEndSection": 994, "text": "In our series, 19 different de novo MECP2 mutations, eight of which were previously unreported, were found in 35 out of 50 Rett girls (70%)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11462237", "endSection": "sections.0" }, { "offsetInBeginSection": 306, "offsetInEndSection": 542, "text": "Causative mutations in the MeCP2 gene were identified in 63% of patients, representing a total of 30 different mutations. Mutations were identified in 72% of patients with classical RTT and one third of atypical cases studied (8 of 25).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11402105", "endSection": "sections.0" }, { "offsetInBeginSection": 426, "offsetInEndSection": 506, "text": "We have identified 15 different MECP2 mutations in 26 of 30 Danish RTT patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11313756", "endSection": "sections.0" } ] }, { "body": "What is the treatment of Riedel disease (thyroiditis)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11014014", "http://www.ncbi.nlm.nih.gov/pubmed/21568724", "http://www.ncbi.nlm.nih.gov/pubmed/3287769", "http://www.ncbi.nlm.nih.gov/pubmed/22210556", "http://www.ncbi.nlm.nih.gov/pubmed/8120524" ], "ideal_answer": [ "Riedel thyroiditis is a rare disorder related to a systemic extracervical fibrotic process of unknown origin. The tratment of choice is the surgical treatment: Corticosteroids may be also useful" ], "type": "summary", "id": "517541e08ed59a060a00002a", "snippets": [ { "offsetInBeginSection": 1530, "offsetInEndSection": 1732, "text": "IFT often is associated with a systemic extracervical fibrotic process and tobacco use. Attempted thyroid resection often results in postoperative complications. Long-term follow-up showed no deaths fro", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21568724", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Riedel's invasive fibrous thyroiditis is a rare disorder of unknown origin with progressive extension and invasion of adjacent structures.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11014014", "endSection": "sections.0" }, { "offsetInBeginSection": 139, "offsetInEndSection": 287, "text": "Clinically it is impossible to distinguish between Riedel's/thyroiditis and other diseases as undifferentiated carcinoma, Hashimoto's disease etc...", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11014014", "endSection": "sections.0" }, { "offsetInBeginSection": 436, "offsetInEndSection": 888, "text": "Surgical treatment depends on the stage of the disease, when both lobes are involved generous wedge resection of the isthmus may be the treatment of choice to relieve tracheal compression; in earlier stages radical operation are considered. Corticosteroid treatment in Riedel's thyroiditis, as multifocal disease has been successfully used. Other drugs with antifibrosing actions have also utilised in small groups of patients with encouraging results.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11014014", "endSection": "sections.0" } ] }, { "body": "What is the link between Dax1 and Esrrb?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23508100" ], "ideal_answer": [ "Dax1 associates with Esrrb and regulates its function in embryonic stem cells", "Dax1 associates with Esrrb and regulates its function in embryonic stem cells." ], "exact_answer": [ "Dax1 associates with Esrrb and regulates its function in embryonic stem cells." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057137" ], "type": "factoid", "id": "56a8ee75a17756b72f000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Dax1 associates with Esrrb and regulates its function in embryonic stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "title" }, { "offsetInBeginSection": 176, "offsetInEndSection": 685, "text": "Nuclear hormone receptor Dax1 is one of the crucial factors in the network. Here, we identified an orphan nuclear receptor, Esrrb (estrogen-related receptor beta), as a Dax1-interacting protein. Interaction of Dax1 and Esrrb was mediated through LXXLL motifs of Dax1 and the activation- and ligand-binding domains of Esrrb. Furthermore, Esrrb enhanced the promoter activity of the Dax1 gene via direct binding to Esrrb-binding site 1 (ERRE1, where \"ERRE\" represents \"Esrrb-responsive element\") of the promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1405, "text": " We also found that the transcriptional activity of Esrrb was repressed by Dax1. Furthermore, we revealed that Oct3/4, Dax1, and Esrrb have a competitive inhibition capacity for each complex. These data, together with previous findings, suggest that Dax1 functions as a negative regulator of Esrrb and Oct3/4, and these molecules form a regulatory loop for controlling the pluripotency and self-renewal capacity of ES cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1272, "text": "Expression of Dax1 was suppressed followed by Oct3/4 repression; however, overexpression of Esrrb maintained expression of Dax1 even in the absence of Oct3/4, indicating that Dax1 is a direct downstream target of Esrrb and that Esrrb can regulate Dax1 expression in an Oct3/4-independent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 624, "text": "Interaction of Dax1 and Esrrb was mediated through LXXLL motifs of Dax1 and the activation- and ligand-binding domains of Esrrb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 868, "text": "Furthermore, Esrrb enhanced the promoter activity of the Dax1 gene via direct binding to Esrrb-binding site 1 (ERRE1, where \"ERRE\" represents \"Esrrb-responsive element\") of the promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Dax1 associates with Esrrb and regulates its function in embryonic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "title" }, { "offsetInBeginSection": 371, "offsetInEndSection": 983, "text": "Interaction of Dax1 and Esrrb was mediated through LXXLL motifs of Dax1 and the activation- and ligand-binding domains of Esrrb. Furthermore, Esrrb enhanced the promoter activity of the Dax1 gene via direct binding to Esrrb-binding site 1 (ERRE1, where \"ERRE\" represents \"Esrrb-responsive element\") of the promoter. Expression of Dax1 was suppressed followed by Oct3/4 repression; however, overexpression of Esrrb maintained expression of Dax1 even in the absence of Oct3/4, indicating that Dax1 is a direct downstream target of Esrrb and that Esrrb can regulate Dax1 expression in an Oct3/4-independent manner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 687, "text": "Interaction of Dax1 and Esrrb was mediated through LXXLL motifs of Dax1 and the activation- and ligand-binding domains of Esrrb. Furthermore, Esrrb enhanced the promoter activity of the Dax1 gene via direct binding to Esrrb-binding site 1 (ERRE1, where \"ERRE\" represents \"Esrrb-responsive element\") of the promoter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 1003, "text": "Furthermore, Esrrb enhanced the promoter activity of the Dax1 gene via direct binding to Esrrb-binding site 1 (ERRE1, where "ERRE" represents "Esrrb-responsive element") of the promoter. Expression of Dax1 was suppressed followed by Oct3/4 repression; however, overexpression of Esrrb maintained expression of Dax1 even in the absence of Oct3/4, indicating that Dax1 is a direct downstream target of Esrrb and that Esrrb can regulate Dax1 expression in an Oct3/4-independent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 707, "text": "Interaction of Dax1 and Esrrb was mediated through LXXLL motifs of Dax1 and the activation- and ligand-binding domains of Esrrb. Furthermore, Esrrb enhanced the promoter activity of the Dax1 gene via direct binding to Esrrb-binding site 1 (ERRE1, where "ERRE" represents "Esrrb-responsive element") of the promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 500, "text": "Here, we identified an orphan nuclear receptor, Esrrb (estrogen-related receptor beta), as a Dax1-interacting protein. Interaction of Dax1 and Esrrb was mediated through LXXLL motifs of Dax1 and the activation- and ligand-binding domains of Esrrb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" } ] }, { "body": "What is dovitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23228017", "http://www.ncbi.nlm.nih.gov/pubmed/24908540", "http://www.ncbi.nlm.nih.gov/pubmed/21521775", "http://www.ncbi.nlm.nih.gov/pubmed/23443805", "http://www.ncbi.nlm.nih.gov/pubmed/24495750", "http://www.ncbi.nlm.nih.gov/pubmed/21976540", "http://www.ncbi.nlm.nih.gov/pubmed/25023489", "http://www.ncbi.nlm.nih.gov/pubmed/22180308", "http://www.ncbi.nlm.nih.gov/pubmed/24238094", "http://www.ncbi.nlm.nih.gov/pubmed/23010851", "http://www.ncbi.nlm.nih.gov/pubmed/23339124", "http://www.ncbi.nlm.nih.gov/pubmed/26070683", "http://www.ncbi.nlm.nih.gov/pubmed/23041231", "http://www.ncbi.nlm.nih.gov/pubmed/23400739", "http://www.ncbi.nlm.nih.gov/pubmed/24448819", "http://www.ncbi.nlm.nih.gov/pubmed/22230479", "http://www.ncbi.nlm.nih.gov/pubmed/24556040" ], "ideal_answer": [ "Dovitinib (TKI258) is a tyrosine kinase receptor inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR)." ], "exact_answer": [ "tyrosine kinase receptor inhibitor" ], "type": "factoid", "id": "56d04a533975bb303a000010", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 312, "text": "This phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26070683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Disposition and metabolism of 14C-dovitinib (TKI258), an inhibitor of FGFR and VEGFR, after oral administration in patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23010851", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Phase I/II and pharmacodynamic study of dovitinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21976540", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23339124", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The anticancer multi-kinase inhibitor dovitinib also targets topoisomerase I and topoisomerase II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041231", "endSection": "title" } ] }, { "body": "Are DNA helicases involved in progeroid syndromes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10984715", "http://www.ncbi.nlm.nih.gov/pubmed/17131053", "http://www.ncbi.nlm.nih.gov/pubmed/16987878", "http://www.ncbi.nlm.nih.gov/pubmed/15743670", "http://www.ncbi.nlm.nih.gov/pubmed/15734684" ], "ideal_answer": [ "Yes, mutations in genes coding for DNA helicases were found to induce progeroid syndromes, such as Werner syndrome (WS) or Bloom syndrome (BS)." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004265", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033202", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003057", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003678", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053484" ], "type": "yesno", "id": "5319a752b166e2b806000027", "snippets": [ { "offsetInBeginSection": 349, "offsetInEndSection": 510, "text": "Among these syndromes, relevant advances have recently been made in Werner syndrome, one of several progeroid syndromes characterized by defective DNA helicases,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17131053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Progeroid syndromes (PSs) constitute a group of disorders characterized by clinical features mimicking physiological aging at an early age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16987878", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 928, "text": "However, all the characterized PSs enter in the field of rare monogenic disorders and several causative genes have been identified. These can be separated in subcategories corresponding to (i) genes encoding DNA repair factors, in particular, DNA helicases, and (ii) genes affecting the structure or post-translational maturation of lamin A, a major nuclear component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16987878", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 710, "text": "None of the known progerias represents true precocious ageing. Some of them, including Werner (WS), Bloom (BS), and Rothmund-Thomson syndromes (RTS) as well as combined xeroderma pigmentosa-Cockayne syndrome (XP-CS) are characterised by features resembling precocious ageing and the increased risk of malignant disease. Such phenotypes result from the mutations of the genes encoding proteins involved in the maintenance of genomic integrity, in most cases DNA helicases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15743670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or \"normative\" aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15734684", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 476, "text": "The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15734684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Progeria and progeroid syndromes are characterized by the earlier onset of complex senescent phenotypes. WRN was originally identified as a gene responsible for Werner syndrome (WS; \"Progeria of Adults\"). The WRN gene product has RecQ-type helicase domains in the central region of the protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10984715", "endSection": "abstract" } ] }, { "body": "List the diseases for which there are point-of-care breath tests", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20805989", "http://www.ncbi.nlm.nih.gov/pubmed/20973886", "http://www.ncbi.nlm.nih.gov/pubmed/18657870", "http://www.ncbi.nlm.nih.gov/pubmed/15963485", "http://www.ncbi.nlm.nih.gov/pubmed/23462278", "http://www.ncbi.nlm.nih.gov/pubmed/16377649", "http://www.ncbi.nlm.nih.gov/pubmed/16887493", "http://www.ncbi.nlm.nih.gov/pubmed/21619467", "http://www.ncbi.nlm.nih.gov/pubmed/22134047", "http://www.ncbi.nlm.nih.gov/pubmed/20495659", "http://www.ncbi.nlm.nih.gov/pubmed/19248196", "http://www.ncbi.nlm.nih.gov/pubmed/15006940", "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "http://www.ncbi.nlm.nih.gov/pubmed/22771606", "http://www.ncbi.nlm.nih.gov/pubmed/24305596", "http://www.ncbi.nlm.nih.gov/pubmed/20507559", "http://www.ncbi.nlm.nih.gov/pubmed/18619827", "http://www.ncbi.nlm.nih.gov/pubmed/11215996", "http://www.ncbi.nlm.nih.gov/pubmed/17868431", "http://www.ncbi.nlm.nih.gov/pubmed/23708532", "http://www.ncbi.nlm.nih.gov/pubmed/24299143", "http://www.ncbi.nlm.nih.gov/pubmed/22209594", "http://www.ncbi.nlm.nih.gov/pubmed/12877652", "http://www.ncbi.nlm.nih.gov/pubmed/23772662", "http://www.ncbi.nlm.nih.gov/pubmed/16326150", "http://www.ncbi.nlm.nih.gov/pubmed/23601567", "http://www.ncbi.nlm.nih.gov/pubmed/18045887", "http://www.ncbi.nlm.nih.gov/pubmed/10443811", "http://www.ncbi.nlm.nih.gov/pubmed/23471596", "http://www.ncbi.nlm.nih.gov/pubmed/18420865", "http://www.ncbi.nlm.nih.gov/pubmed/19717480", "http://www.ncbi.nlm.nih.gov/pubmed/18367951", "http://www.ncbi.nlm.nih.gov/pubmed/12540328" ], "ideal_answer": [ "Point of care breath tests are available for lung cancer, pulmonary embolism, respiratory distress syndrome, methanol intoxication, kidney diseases, liver diseases, Helicobacter pylori infection, asthma, sepsis, heart failure, diabetes and tuberculosis." ], "exact_answer": [ [ "lung cancer" ], [ "pulmonary embolism" ], [ "respiratory distress syndrome" ], [ "methanol intoxication" ], [ "kidney diseases" ], [ "liver diseases" ], [ "Helicobacter pylori infection" ], [ "asthma" ], [ "sepsis" ], [ "heart failure" ], [ "diabetes" ], [ "tuberculosis" ] ], "type": "list", "id": "551829a76487737b43000009", "snippets": [ { "offsetInBeginSection": 861, "offsetInEndSection": 1145, "text": "Additionally, we try to clarify controversial issues concerning possible experimental malpractice in the field, and propose ways to translate the basic science results as well as the mechanistic understanding to tools (sensors) that could serve as point-of-care diagnostics of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24305596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Point of care monitoring of hemodialysis patients with a breath ammonia measurement device based on printed polyaniline nanoparticle sensors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24299143", "endSection": "title" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1152, "text": " Excellent intraindividual correlations were demonstrated between breath ammonia and BUN (0.86 to 0.96), which demonstrates the possibility of using low cost point of care breath ammonia systems as a noninvasive means of monitoring kidney dysfunction and treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24299143", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 452, "text": "Recently, fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker for the assessment and management of asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23462278", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 374, "text": "Here we discuss the potential of adapting a technology from the electronics industry, surface acoustic wave (SAW) sensors, for diagnosis of multiple markers of sepsis in real time, using non-invasive assays of exhaled breath condensate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23471596", "endSection": "abstract" }, { "offsetInBeginSection": 1555, "offsetInEndSection": 1674, "text": "Together these data indicate that FeNO testing has an important role in the assessment and management of adult asthma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23601567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Measurement of acetone in human breath samples has been previously shown to provide significant non-invasive diagnostic insight into the control of a patient's diabetic condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23708532", "endSection": "abstract" }, { "offsetInBeginSection": 1374, "offsetInEndSection": 1487, "text": " Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and treatment response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22771606", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1678, "text": "These animal model results suggest that exhaled breath can be used as a point-of-care tool for the diagnosis and monitoring of sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22209594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Point-of-care breath test for biomarkers of active pulmonary tuberculosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "RATIONALE: Volatile organic compounds (VOCs) in breath provide biomarkers of tuberculosis (TB) because Mycobacterium tuberculosis manufactures VOC metabolites that are detectable in the breath of infected patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "endSection": "abstract" }, { "offsetInBeginSection": 1730, "offsetInEndSection": 1862, "text": "CONCLUSIONS: A six-minute point-of-care breath test for volatile biomarkers accurately identified subjects with active pulmonary TB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Selected ion flow tube-mass spectrometry (SIFT-MS) can measure volatile compounds in breath on-line in real time and has the potential to provide accurate breath tests for a number of inflammatory, infectious and metabolic diseases, including diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134047", "endSection": "abstract" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1252, "text": "Breath analysis by SIFT-MS offers a rapid, reproducible and easily performed measurement of acetone concentration in ambulatory patients with type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134047", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1309, "text": "IGR is a new approach for non-invasive cardiac output measurement in mechanically ventilated individuals, but requires further investigation for clinical use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619467", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1203, "text": "The liver metabolic breath test relies on measuring exhaled (13) C tagged methacetin, which is metabolized only by the liver. Measuring this liver-specific substrate by means of molecular correlation spectroscopy is a rapid, non-invasive method for assessing liver function at the point-of-care. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20973886", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1562, "text": "Our recent findings regarding the ability of point-of-care (13) C MBT to assess the hepatic functional reserve in patients with acute and chronic liver disease are reviewed along with suggested treatment algorithms for common liver disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20973886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805989", "endSection": "title" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1576, "text": "CONCLUSIONS/SIGNIFICANCE: Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805989", "endSection": "abstract" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1487, "text": "CONCLUSIONS: The non-invasive real-time BreathID GBT reliably assesses changes in liver glucose metabolism, and the degree of insulin resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507559", "endSection": "abstract" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1343, "text": "DISCUSSION: The LiMAx test can validly determine liver function capacity and is feasible in every clinical situation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20495659", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1289, "text": "A P(ET,CO(2)) of >or=36 mmHg may reliably exclude PE. Accuracy is augmented by combination with Wells score. P( ET,CO(2)) should be prospectively compared to D-dimer in accuracy and simplicity to exclude PE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19717480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Point-of-care continuous (13)C-methacetin breath test improves decision making in acute liver disease: results of a pilot clinical trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19248196", "endSection": "title" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1108, "text": "CONCLUSION: The (13)C-MBT provides a rapid, non-invasive assessment of liver function in acute severe liver disease of diverse etiologies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19248196", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1206, "text": "CONCLUSION: The determination of CO by IGR and CWD revealed a good agreement and reproducibility with a low rate of impossible measurements, suggesting that IGR and CWD can be used interchangeably in the clinical setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18657870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "BACKGROUND: Exhaled NO (FE(NO)) is a useful biomarker for the monitoring of asthma control and response to therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18619827", "endSection": "abstract" }, { "offsetInBeginSection": 1558, "offsetInEndSection": 1896, "text": "A high percentage of patients with different severities of asthma and regardless of their treatment with ICS and current smoking habit (current and/or ex-smokers) had highly elevated FE(NO) values, suggesting that their current therapy was possibly insufficient to control the underlying degree of airway inflammation and asthma symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18619827", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 602, "text": "H. pylori-positive status was defined by positivity on at least 2 tests: a commercial H. pylori stool antigen enzyme immunoassay, an immunoglobulin G antibody enzyme immunoassay, and the C-urea breath test", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18367951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "End-tidal carbon dioxide measurements in children with acute asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045887", "endSection": "title" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1539, "text": "CONCLUSIONS: Noninvasive bedside measurement of EtCO2 values among children with acute asthma is feasible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Review article: the assessment of liver function using breath tests.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868431", "endSection": "title" }, { "offsetInBeginSection": 394, "offsetInEndSection": 548, "text": "The recent development of a real-time, point-of-care liver function breath test has made it straightforward to assess the metabolic function of the liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868431", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 985, "text": "RESULTS: The (13)C-methacetin breath test enables accurate follow-up of patients with acute or chronic liver damage, where overall hepatic function is significantly suppressed by known causes of liver disorders, including acute, sub-acute or chronic conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868431", "endSection": "abstract" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1294, "text": "CONCLUSIONS: Breath testing that provides continuous quantification of methacetin metabolism may be a sensitive tool for the diagnosis and follow-up of patients with liver disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868431", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 497, "text": " A multi-center study in a multi-ethnic population compared the RAPIRUN urine antibody test with the (13)C-urea breath test (C-UBT) and a traditional serologic test, the high-molecular-weight cell-associated protein enzyme immunoassay (HM-CAP EIA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16887493", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1666, "text": "CONCLUSION: EGA provided non-invasive, accurate, continuous, high-resolution COHb% measurements. Applying EGA to carboxyhaemoglobin dilution, we achieved RCV measurements with accuracy equivalent to that of CO-haemoximetry, with one-fifth of the COB infusion volume.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16377649", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1162, "text": " These results suggest that the IR device, which is small, light-weight, and rugged may enable the foreign gas uptake method to be used in clinical, field, and point-of-care settings for Q (T) measurement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16326150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "UNLABELLED: The 13C-urea breath test provides non-invasive testing for Helicobacter pylori infection with the possibility of analysis at the point of care. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15963485", "endSection": "abstract" }, { "offsetInBeginSection": 1827, "offsetInEndSection": 1968, "text": "CONCLUSION: Fdlate, a variable of VCap, had a statistically better diagnostic performance in suspected PE than the PaCO(2)-EtCO(2) gradient. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006940", "endSection": "abstract" }, { "offsetInBeginSection": 1451, "offsetInEndSection": 1566, "text": " In conclusion, the investigated rebreathing system allows for a non-invasive determination of PBF at the bedside. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12877652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Non-invasive measurement of pulmonary blood flow during prone positioning in patients with early acute respiratory distress syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12877652", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The 13C-urea breath test provides accurate, noninvasive diagnosis of active Helicobacter pylori infection and can document posttherapy cure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12540328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was tested for the diagnosis of methanol intoxications. Breath analysis with FT-IR was fast and easy, and no sample preparation was needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11215996", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 969, "text": "CONCLUSIONS: The Fd(late) is a valuable tool for bedside screening of PE in surgical patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443811", "endSection": "abstract" } ] }, { "body": "Is there association of matrix metalloproteinases with behaviour of pituitary adenomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10634397", "http://www.ncbi.nlm.nih.gov/pubmed/10598711", "http://www.ncbi.nlm.nih.gov/pubmed/12508658", "http://www.ncbi.nlm.nih.gov/pubmed/18493720", "http://www.ncbi.nlm.nih.gov/pubmed/16172741", "http://www.ncbi.nlm.nih.gov/pubmed/16167532", "http://www.ncbi.nlm.nih.gov/pubmed/16078111", "http://www.ncbi.nlm.nih.gov/pubmed/22822048", "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "http://www.ncbi.nlm.nih.gov/pubmed/10946906", "http://www.ncbi.nlm.nih.gov/pubmed/12904990" ], "ideal_answer": [ "Yes, there is evidence to suggest that matrix metalloproteinases are associated with more aggressive of pituitary adenomas." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010911", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020782", "http://www.disease-ontology.org/api/metadata/DOID:3829" ], "type": "yesno", "id": "56c1d85eef6e394741000035", "snippets": [ { "offsetInBeginSection": 313, "offsetInEndSection": 633, "text": "While detailed histological subtyping remains the best independent predictor of aggressive behavior in the majority of cases, evidence suggests that the additional analyses of FGFR4, MMP, PTTG, Ki-67, p53, and deletions in chromosome 11 may contribute to decisions concerning management of aggressive pituitary adenomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22822048", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1236, "text": "We observed elevation of MMP-2 and -9 expression and consequent 3-D cell invasion in cells under-expressing RECK. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18493720", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 384, "text": " Based on the significance of matrix metalloproteinases (MMPs) for tumor growth and angiogenesis, we have studied the effect of batimastat (BB-94), a synthetic MMPs inhibitor (MMPI) on the progression of prolactin-secreting pituitary adenoma in rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Inhibition of estrogen-induced pituitary tumor growth and angiogenesis in Fischer 344 rats by the matrix metalloproteinase inhibitor batimastat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "endSection": "title" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1258, "text": "The results of our study provide evidence for an inhibitory effect of batimastat, a synthetic MMPI, on the growth and angiogenesis in an experimental model of human prolactinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1746, "text": "In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16172741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12904990", "endSection": "abstract" }, { "offsetInBeginSection": 1648, "offsetInEndSection": 1712, "text": "We found no correlation of MMP-9 expression and tumour invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12904990", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 599, "text": "The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12508658", "endSection": "abstract" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1721, "text": "CONCLUSIONS: TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12508658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that are able to degrade the extracellular matrix and allow angiogenesis and tumor invasion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10946906", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 2039, "text": "MMP-9 expression did not differ between noninvasive tumors and normal pituitary gland, or between different sized prolactinomas. MMP-9 expression was related to aggressive tumor behavior. It was higher in invasive macroprolactinomas (P = 0.003) when compared with noninvasive macroprolactinomas or the normal anterior pituitary gland. In addition, although there was no difference in whether MMP-9 was present or not when nonfunctioning adenomas that recurred were compared with those that did not, samples of recurrent tumor at the second presentation were more likely to express MMP-9 (P = 0.01). Pituitary carcinomas were significantly more likely to be MMP-9 positive compared with normal anterior pituitary gland (P = 0.05), but there was no difference from invasive adenomas. Angiogenesis assessed by vascular density was related to MMP-9 expression (P<0.05). In summary, we have shown the presence of MMP-9 expression in some invasive and recurrent pituitary adenomas, and in the majority of pituitary carcinoma. The mechanisms whereby MMP-9 expression influences tumor recurrence and invasiveness, and its association with angiogenesis, remains to be elucidated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10946906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10634397", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1022, "text": "CONCLUSION: No correlation could be established between the invasive potential of tumors and MMP-1, -2, and -3 expression levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10598711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Matrix metalloproteinase 2 and 9 expression correlated with cavernous sinus invasion of pituitary adenomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16167532", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12904990", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 818, "text": "We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10634397", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 600, "text": "The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12508658", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 624, "text": "We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10634397", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 1101, "text": "There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P < 0.001) and MMP-9 (P < 0.001). But c-myc LI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 vs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16078111", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1569, "text": "nm23 and MMP-9 have associations with invasiveness of pituitary adenomas,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16078111", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1747, "text": "Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16172741", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 992, "text": "There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P < 0.001) and MMP-9 (P < 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16078111", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1599, "text": "Although our study has shown that MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas, they are lack of specificity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16078111", "endSection": "abstract" } ] }, { "body": "What is the evolutionary process described by the \"Muller's ratchet\" model?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14741203", "http://www.ncbi.nlm.nih.gov/pubmed/11164046", "http://www.ncbi.nlm.nih.gov/pubmed/16957730", "http://www.ncbi.nlm.nih.gov/pubmed/8380072", "http://www.ncbi.nlm.nih.gov/pubmed/8365659", "http://www.ncbi.nlm.nih.gov/pubmed/20657178", "http://www.ncbi.nlm.nih.gov/pubmed/22649084", "http://www.ncbi.nlm.nih.gov/pubmed/24244123", "http://www.ncbi.nlm.nih.gov/pubmed/8570657", "http://www.ncbi.nlm.nih.gov/pubmed/16709275", "http://www.ncbi.nlm.nih.gov/pubmed/16924405", "http://www.ncbi.nlm.nih.gov/pubmed/18366680", "http://www.ncbi.nlm.nih.gov/pubmed/17720933", "http://www.ncbi.nlm.nih.gov/pubmed/23046686", "http://www.ncbi.nlm.nih.gov/pubmed/23100362", "http://www.ncbi.nlm.nih.gov/pubmed/12967275", "http://www.ncbi.nlm.nih.gov/pubmed/18302772", "http://www.ncbi.nlm.nih.gov/pubmed/19305500", "http://www.ncbi.nlm.nih.gov/pubmed/2247152", "http://www.ncbi.nlm.nih.gov/pubmed/4448362", "http://www.ncbi.nlm.nih.gov/pubmed/22661327", "http://www.ncbi.nlm.nih.gov/pubmed/23028310", "http://www.ncbi.nlm.nih.gov/pubmed/9369098" ], "ideal_answer": [ "The vast majority of mutations are deleterious and are eliminated by purifying selection. Yet in finite populations, purifying selection cannot completely prevent the accumulation of deleterious mutations. Muller's ratchet is a paradigmatic model for the accumulation of deleterious mutations in a population of finite size, due to genetic drift. Muller's ratchet suggests that population bottlenecks, which may constrain the genetic diversity of a population, could lead to extinction of all individuals with the least number of deleterious mutations, due to a stochastic fluctuation. When the most-fit class of genotypes is lost, it is lost irreversibly." ], "type": "summary", "id": "554a0cadf35db7552600000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Muller's ratchet is a paradigmatic model for the accumulation of deleterious mutations in a population of finite size. A click of the ratchet occurs when all individuals with the least number of deleterious mutations are lost irreversibly due to a stochastic fluctuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Population bottlenecks can have major effects in the evolution of RNA viruses, but their possible influence in the evolution of DNA viruses is largely unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100362", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 222, "text": "The accumulation of deleterious mutations of a population directly contributes to the fate as to how long the population would exist, a process often described as Muller's ratchet with the absorbing phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046686", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 515, "text": "Genetic diversity is thought to be important in allowing RNA viruses to explore sequence space, facilitating adaptation to changing environments and hosts. Some arboviruses that infect both a mosquito vector and a mammalian host are known to experience population bottlenecks in their vectors, which may constrain their genetic diversity and could potentially lead to extinction events via Muller's ratchet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028310", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The accumulation of deleterious mutations is driven by rare fluctuations that lead to the loss of all mutation free individuals, a process known as Muller's ratchet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22649084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "The vast majority of mutations are deleterious and are eliminated by purifying selection. Yet in finite asexual populations, purifying selection cannot completely prevent the accumulation of deleterious mutations due to Muller's ratchet: once lost by stochastic drift, the most-fit class of genotypes is lost forever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661327", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 261, "text": "Primary bacterial endosymbionts of insects (p-endosymbionts) are thought to be undergoing the process of Muller's ratchet where they accrue slightly deleterious mutations due to genetic drift in small populations with negligible recombination rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19305500", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1108, "text": "Computer simulations of substitution of favorable mutants and of the long-term increase of deleterious mutants verified the essential correctness of the original Fisher-Muller argument and the reality of the Muller ratchet mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4448362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "The theory of Muller' Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18302772", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 875, "text": "It also predicts the \"ratchet mechanism\" discovered by Muller, who pointed out that deleterious mutants would more readily increase in a population without recombination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4448362", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 617, "text": "We also demonstrate that during repeated genetic bottleneck passages, accumulation of deleterious mutations does occur in a stepwise (ratchet-like) manner as originally proposed by Muller.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8380072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Muller proposed that an asexual organism will inevitably accumulate deleterious mutations, resulting in an increase of the mutational load and an inexorable, ratchet-like, loss of the least mutated class [Muller, H.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8570657", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 540, "text": "In asexual populations, as Muller noted, the loss is irreversible and the load of deleterious mutations increases in a ratchet-like manner with the successive loss of the least-mutated individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2247152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "BACKGROUND: The accumulation of deleterious mutations of a population directly contributes to the fate as to how long the population would exist, a process often described as Mullers ratchet with the absorbing phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The accumulation of deleterious mutations is driven by rare fluctuations that lead to the loss of all mutation free individuals, a process known as Mullers ratchet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22649084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Deleterious mutations can accumulate in asexual haploid genomes through the process known as Muller's ratchet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17720933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Deleterious mutations can accumulate in asexual haploid genomes through the process known as Muller's ratchet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17720933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The accumulation of deleterious mutations of a population directly contributes to the fate as to how long the population would exist, a process often described as Muller's ratchet with the absorbing phenomenon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046686", "endSection": "abstract" } ] }, { "body": "Which heat shock protein is found to be upregulated during Hsp90 inhibition?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23023377", "http://www.ncbi.nlm.nih.gov/pubmed/24100469", "http://www.ncbi.nlm.nih.gov/pubmed/20015528" ], "ideal_answer": [ "HSP90 inhibition was found to be associated with induction of HSP70 expression." ], "exact_answer": [ "HSP70" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006986", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018841", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018840", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006360", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042026", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015854", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034620", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018869" ], "type": "factoid", "id": "534abe8aaeec6fbd07000013", "snippets": [ { "offsetInBeginSection": 935, "offsetInEndSection": 1110, "text": "HSP90 inhibition was associated with decreased neuroendocrine ErbB and IGF-I receptor expression, decreased Erk and Akt phospho-rylation and the induction of HSP70 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24100469", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1001, "text": "Inhibition of Hsp90 upregulated the expression of Hsp70 and Hsp70-bound Nox2, 5 and promoted degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23023377", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1080, "text": "Conversely, inhibition of HSP90 significantly increased the expression of both VEGF and HGF mRNA, and induced HSP70 protein in PHH cultures in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20015528", "endSection": "abstract" } ] }, { "body": "Which gene is responsible for the development of Sotos syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25510705", "http://www.ncbi.nlm.nih.gov/pubmed/25852445", "http://www.ncbi.nlm.nih.gov/pubmed/21567906", "http://www.ncbi.nlm.nih.gov/pubmed/26043501", "http://www.ncbi.nlm.nih.gov/pubmed/23190751", "http://www.ncbi.nlm.nih.gov/pubmed/14571271", "http://www.ncbi.nlm.nih.gov/pubmed/24192683", "http://www.ncbi.nlm.nih.gov/pubmed/22012791", "http://www.ncbi.nlm.nih.gov/pubmed/16232326", "http://www.ncbi.nlm.nih.gov/pubmed/21834033", "http://www.ncbi.nlm.nih.gov/pubmed/20420030", "http://www.ncbi.nlm.nih.gov/pubmed/16010675" ], "ideal_answer": [ "Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS.", "Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability. This disorder is caused by mutations or deletions in NSD1 gene" ], "exact_answer": [ "NSD1 gene" ], "type": "factoid", "id": "571f33bd0fd6f91b68000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability. This disorder is caused by mutations or deletions in NSD1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26043501", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25852445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90% of cases of Sotos syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20420030", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 469, "text": "The NSD1 gene was recently found to be responsible for Sotos syndrome, and more than 150 patients with NSD1 alterations have been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16010675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Recently, deletions encompassing the nuclear receptor binding SET-Domain 1 (NSD1) gene have been described as the major cause of Japanese patients with the Sotos syndrome, whereas point mutations have been identified in the majority of European Sotos syndrome patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14571271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14571271", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16232326", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Two cases of Sotos syndrome with novel mutations of the NSD1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20420030", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90% of cases of Sotos syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20420030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Haploinsufficiency of the NSD1 gene due to 5q35 microdeletions or intragenic mutations is the major cause of Sotos syndrome characterized by generalized overgrowth, large hands and feet with advanced bone age, craniofacial dysmorphic features, learning disability, and possible susceptibility to tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21567906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16232326", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 282, "text": "Haploinsufficiency of the NSD1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16232326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Haploinsufficiency of the NSD1 gene due to 5q35 microdeletions or intragenic mutations is the major cause of Sotos syndrome characterized by generalized overgrowth, large hands and feet with advanced bone age, craniofacial dysmorphic features, learning disability, and possible susceptibility to tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21567906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190751", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Craniofacial and oral features of Sotos syndrome: differences in patients with submicroscopic deletion and mutation of NSD1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22012791", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Prenatal diagnosis and molecular cytogenetic characterization of a 1.07-Mb microdeletion at 5q35.2-q35.3 associated with NSD1 haploinsufficiency and Sotos syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510705", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 353, "text": "Autosomal dominant mutations and deletions of the nuclear receptor set domain gene (NSD1), which is located at chromosome 5q35, are responsible for most of the cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24192683", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 312, "text": "There are two types of mutations that cause NSD1 haploinsufficiency: mutations within the NSD1 gene (mutation type) and a 5q35 submicroscopic deletion encompassing the entire NSD1 gene (deletion type). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22012791", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Sotos syndrome is a rare genetic disorder characterized by overgrowth associated with macrocephaly and delayed psychomotor development. Patients with Sotos syndrome show 5q35 deletions involving NSD1 or its point mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21834033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Mutations in NSD1 are responsible for Sotos syndrome,", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14571271", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90% of cases of Sotos syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20420030", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 330, "text": "The NSD1 gene was recently found to be responsible for Sotos syndrome, and more than 150 patients with NSD1 alterations have been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16010675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14571271", "endSection": "title" } ] }, { "body": "What is the name for anorexia in gymnasts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10551340", "http://www.ncbi.nlm.nih.gov/pubmed/24240086" ], "ideal_answer": [ "Anorexia athletica" ], "exact_answer": [ "Anorexia Athletica" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006173", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000855", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000856" ], "type": "factoid", "id": "53617eeb7d100faa0900000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Elite Rhythmic Gymnasts (RGs) constitute a unique metabolic model and they are prone to developing Anorexia Athletica.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240086", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 273, "text": "We studied 13 female juvenile elite gymnasts with anorexia athletica (AA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10551340", "endSection": "abstract" } ] }, { "body": "Is Vitamin D deficiency in pregnant women associated with gestational diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23452283", "http://www.ncbi.nlm.nih.gov/pubmed/20962313", "http://www.ncbi.nlm.nih.gov/pubmed/19692182", "http://www.ncbi.nlm.nih.gov/pubmed/22548949", "http://www.ncbi.nlm.nih.gov/pubmed/18544105", "http://www.ncbi.nlm.nih.gov/pubmed/14633808", "http://www.ncbi.nlm.nih.gov/pubmed/22717271", "http://www.ncbi.nlm.nih.gov/pubmed/21658195", "http://www.ncbi.nlm.nih.gov/pubmed/18285809", "http://www.ncbi.nlm.nih.gov/pubmed/19015731", "http://www.ncbi.nlm.nih.gov/pubmed/21470081", "http://www.ncbi.nlm.nih.gov/pubmed/21663527", "http://www.ncbi.nlm.nih.gov/pubmed/22150921", "http://www.ncbi.nlm.nih.gov/pubmed/23311886", "http://www.ncbi.nlm.nih.gov/pubmed/22606369", "http://www.ncbi.nlm.nih.gov/pubmed/23026519", "http://www.ncbi.nlm.nih.gov/pubmed/23533188", "http://www.ncbi.nlm.nih.gov/pubmed/17607661", "http://www.ncbi.nlm.nih.gov/pubmed/21818838", "http://www.ncbi.nlm.nih.gov/pubmed/21977923", "http://www.ncbi.nlm.nih.gov/pubmed/21454797", "http://www.ncbi.nlm.nih.gov/pubmed/22008274", "http://www.ncbi.nlm.nih.gov/pubmed/22150870" ], "ideal_answer": [ "Yes, there are multiple studies reporting an association between low VitD in pregnancy and impaired glucose tolerance, but it is not entirely clear if this translates directly to the increased risk of Gestational diabetes or via maternal obesity and/or genetic polymorphisms." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11714", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011254", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014808", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002762", "http://www.biosemantics.org/jochem#4250136", "http://www.biosemantics.org/jochem#4250206", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016640", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014807", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004872" ], "type": "yesno", "id": "515def40298dcd4e51000028", "snippets": [ { "offsetInBeginSection": 1104, "offsetInEndSection": 1243, "text": "Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533188", "endSection": "sections.0" }, { "offsetInBeginSection": 1511, "offsetInEndSection": 1598, "text": "Vitamin D insufficiency is associated with an increased risk of gestational diabetes, p", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533188", "endSection": "sections.0" }, { "offsetInBeginSection": 270, "offsetInEndSection": 544, "text": "Therefore, it is important to identify potentially modifiable risk factors for GDM. Accumulating evidence links vitamin D deficiency with abnormal glucose metabolism, and epidemiological studies have shown that women who develop GDM are more likely to be vitamin D deficient", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452283", "endSection": "sections.0" }, { "offsetInBeginSection": 546, "offsetInEndSection": 842, "text": "This review discusses the prevalence, risk factors, and outcomes of GDM and vitamin D deficiency in pregnant women, outlines the possible mechanism of action of vitamin D in glucose homeostasis, and summarizes emerging evidence that associates vitamin D deficiency with the risk of developing GDM", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452283", "endSection": "sections.0" }, { "offsetInBeginSection": 691, "offsetInEndSection": 909, "text": "Women with circulating 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/l in pregnancy experienced an increased risk of preeclampsia [OR 2.09 (95%CI 1.50 -2.90)], gestational diabetes mellitus [OR1.38 (1.12-1.70)]", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23311886", "endSection": "sections.0" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1142, "text": "Low maternal vitamin D levels in pregnancy may be associated with an increased risk of preeclampsia, gestational diabetes mellitus,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23311886", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Association between vitamin D insufficiency and the risk for gestational diabetes mellitus in pregnant Chinese women", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026519", "endSection": "title" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1209, "text": "25OHD insufficiency is very common in Chinese women. Low 25OHD status may be associated with insulin resistance and act as a risk factor for GDM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026519", "endSection": "sections.0" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1156, "text": "Second-trimester 25(OH)D levels were associated inversely with glucose levels after 1-hour 50-g glucose challenge test; low 25(OH)D levels may be associated with increased risk of GDM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22717271", "endSection": "sections.0" }, { "offsetInBeginSection": 509, "offsetInEndSection": 836, "text": "Two hundred sixty-six women were screened. Vitamin D deficiency (25[OH]D <20 ng/mL) was observed in 157 women (59%). We observed an inverse correlation between 25(OH)D levels and hemoglobin A1c, homeostasis model assessment of insulin resistance, serum insulin, and fasting and 1-hour oral glucose tolerance test glucose levels", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22548949", "endSection": "sections.0" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1660, "text": "Lower 25(OH)D levels are associated with disorders of glucose homeostasis and adverse obstetric and newborn outcomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22548949", "endSection": "sections.0" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1481, "text": "An association between mid-gestational 25-hydroxy vitamin D and fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete pregnant population. The correlation between 25-hydroxy vitamin D and \u03b2-cell function suggests that vitamin D may influence glucose metabolism through this mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22150921", "endSection": "sections.0" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1733, "text": "Women with gestational diabetes had significantly lower serum 25-hydroxyvitamin D compared with control subjects (56.3 vs. 62.0 nmol/l, P = 0.018). After adjusting for gestational age and maternal weight, serum 25-hydroxyvitamin D below the top quartile (< 73.5 nmol/l) was associated with a twofold greater likelihood of gestational diabetes (adjusted odds ratio 2.21, 95% confidence interval 1.19-4.13). CONCLUSIONS: Lower vitamin D status in early pregnancy was associated with a significantly increased risk of subsequent gestational diabetes that was independent of race, age, season and maternal weight. This study suggests that vitamin D may influence glucose tolerance during pregnancy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22150870", "endSection": "sections.0" }, { "offsetInBeginSection": 134, "offsetInEndSection": 333, "text": "Vitamin D deficiency among pregnant women is frequent in many populations over the world. It is associated with an increased risk of preeclampsia, gestational diabetes mellitus, and caesarean section", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22008274", "endSection": "sections.0" }, { "offsetInBeginSection": 335, "offsetInEndSection": 463, "text": "Consequences in newborns are low birth weight, neonatal rickets, a risk of neonatal hypocalcemia, asthma and/or type 1 diabetes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22008274", "endSection": "sections.0" }, { "offsetInBeginSection": 1561, "offsetInEndSection": 1844, "text": "A single injection of 300,000 IU of vitamin D3 achieves a 3-month serum 25-hydroxyvitamin D range of 50-80 nmol/l and is an efficient, effective and safe procedure for improving the vitamin status and indices of insulin resistance in mothers with gestational diabetes after delivery.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21977923", "endSection": "sections.0" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1339, "text": "In a cohort of pregnant women with mostly sufficient levels of serum 25(OH)D, vitamin D deficiency was not associated with GDM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21818838", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The aim of the study is evaluating the associations of FokI vitamin D receptor (VDR) gene polymorphisms with gestational diabetes mellitus (GDM), and its relations with postpartum metabolic syndrome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21663527", "endSection": "sections.0" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1281, "text": "Our results indicate a meaningful association between FokI VDR genotypes and an increase risk of GDM in Iranian population as well as its effects on postpartum metabolic syndrome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21663527", "endSection": "sections.0" }, { "offsetInBeginSection": 1649, "offsetInEndSection": 1803, "text": "The first-trimester maternal serum level of 25(OH)D is not altered in women with type 2 diabetes, those who develop GDM or those who deliver LGA neonates.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21658195", "endSection": "sections.0" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1518, "text": "Lower 25(OH)D levels are independently associated with poorer glycaemic control. Future randomised trials are needed to determine whether vitamin D plays a role in glycaemic control in GDM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470081", "endSection": "sections.0" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1302, "text": "These results suggested that rates of vitamin D deficiency are higher among women with IGT/GDM, and the relationship between vitamin D status and glucose tolerance in pregnancy needs further study.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20962313", "endSection": "sections.0" }, { "offsetInBeginSection": 669, "offsetInEndSection": 841, "text": "It appears that vitamin D insufficiency during pregnancy is potentially associated with increased risk of preeclampsia, insulin resistance and gestational diabetes mellitus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19692182", "endSection": "sections.0" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1785, "text": "Mean serum 25OHD concentration was 53.8 +/- 23.9 nmol/l (sd). Ln-25OHD was negatively correlated with serum parathyroid hormone as expected (r -0.24, confidence intervals -0.35 to -0.12). Ln-25OHD was also negatively correlated with fasting plasma glucose (r-0.20, -0.31 to -0.08), fasting insulin (r -0.20, -0.31 to -0.08) and insulin resistance as calculated by homeostasis model assessment (r -0.21, -0.32 to -0.09). The association between fasting glucose and log-transformed 25OHD concentration was of borderline significance after accounting for ethnicity, age and body mass index in multivariate analyses (-0.13, -0.26 to 0.01). The odds ratio of gestational diabetes in women with 25OHD < 50 nmol/l did not reach statistical significance (1.92, 95% confidence interval 0.89-4.17). CONCLUSIONS: Maternal 25OHD concentrations are inversely related to fasting glucose, although further studies are required to establish whether this is independent of the effects of ethnic background.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18544105", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285809", "endSection": "title" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1040, "text": "There was no association between maternal 25(OH)D and gestational diabetes (incidence 7% in women with and without hypovitaminosis D)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285809", "endSection": "sections.0" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1324, "text": "In mothers with hypovitaminosis D, higher 25(OH)D concentrations were associated with lower 30-min glucose concentrations (P=0.03) and higher fasting proinsulin concentrations (P=0.04)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285809", "endSection": "sections.0" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1476, "text": "Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285809", "endSection": "sections.0" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1108, "text": "Total prevalence of vitamin D deficiency (<25 nmol/L) was found in 70.6% of pregnant women. Prevalence of severe vitamin D deficiency (<12.5) in GDM patients was higher than in normoglycaemic pregnancies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17607661", "endSection": "sections.0" }, { "offsetInBeginSection": 1227, "offsetInEndSection": 1410, "text": "These results show that a positive correlation of 25(OH) vitamin D concentrations with insulin sensitivity and vitamin D deficiency could be a confirmative sign of insulin resistance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17607661", "endSection": "sections.0" }, { "offsetInBeginSection": 34, "offsetInEndSection": 230, "text": "was to examine whether maternal dietary intake of vitamin D, omega-3 fatty acids, and omega-6 fatty acids during pregnancy is associated with the appearance of islet autoimmunity (IA) in offspring", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14633808", "endSection": "sections.0" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1628, "text": "Maternal intake of vitamin D via food was significantly associated with a decreased risk of IA appearance in offspring, independent of HLA genotype, family history of type 1 diabetes, presence of gestational diabetes mellitus, and ethnicity (adjusted HR = 0.37; 95% CI 0.17-0.78). Vitamin D intake via supplements, omega-3 fatty acids, and omega-6 fatty acids intake during pregnancy were not associated with appearance of IA in offspring. CONCLUSIONS: Our findings suggest that maternal intake of vitamin D through food during pregnancy may have a protective effect on the appearance of IA in offspring.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14633808", "endSection": "sections.0" } ] }, { "body": "What are the indications for alteplase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19804685", "http://www.ncbi.nlm.nih.gov/pubmed/10172049", "http://www.ncbi.nlm.nih.gov/pubmed/23336348", "http://www.ncbi.nlm.nih.gov/pubmed/7579782", "http://www.ncbi.nlm.nih.gov/pubmed/12450926", "http://www.ncbi.nlm.nih.gov/pubmed/11772304", "http://www.ncbi.nlm.nih.gov/pubmed/11778213", "http://www.ncbi.nlm.nih.gov/pubmed/17656661", "http://www.ncbi.nlm.nih.gov/pubmed/2689138", "http://www.ncbi.nlm.nih.gov/pubmed/23727456", "http://www.ncbi.nlm.nih.gov/pubmed/11794977", "http://www.ncbi.nlm.nih.gov/pubmed/23251746", "http://www.ncbi.nlm.nih.gov/pubmed/1641820", "http://www.ncbi.nlm.nih.gov/pubmed/9385884", "http://www.ncbi.nlm.nih.gov/pubmed/15532135", "http://www.ncbi.nlm.nih.gov/pubmed/10581997", "http://www.ncbi.nlm.nih.gov/pubmed/7549071", "http://www.ncbi.nlm.nih.gov/pubmed/23463740", "http://www.ncbi.nlm.nih.gov/pubmed/11919252", "http://www.ncbi.nlm.nih.gov/pubmed/8521760" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/2894", "o": "Drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/2894", "o": "Cathflo Activase (Alteplase)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/2894", "o": "Intervention #2894 (Drug:Cathflo Activase (Alteplase))" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/48561", "o": "Drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/48561", "o": "Alteplase (Activase, Genentech)" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/48561", "o": "Intervention #48561 (Drug:Alteplase (Activase, Genentech))" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_id", "s": "http://data.linkedct.org/resource/intervention/48561", "o": "48561" } ], "ideal_answer": [ "Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke.\nFood and Drug Administration approval of alteplase for central venous catheter (CVC) occlusions. \nAlteplase is now firmly established as a treatment of choice in the management of acute myocardial infarction. The efficacy of intravenous alteplase in the treatment of pulmonary thromboembolism has also been established and appears to be similar to that of streptokinase and urokinase in this indication and in arterial thrombotic occlusion. However, its use in this latter indication and in other vascular disorders has not been as extensively documented. \nPreliminary data suggest efficacy of alteplase of deep vein thrombosis and arterial thrombotic occlusion." ], "exact_answer": [ [ "ischemic stroke" ], [ "central venous catheter (CVC) occlusions" ], [ "thrombolysis" ], [ "myocardial infarction" ], [ "acute pulmonary embolism" ], [ "deep vein thrombosis" ], [ "limb artery occlusions" ], [ "Ischaemic Stroke" ], [ "Acute Myocardial Infarction", "AMI", "MI" ], [ "Pulmonary Thromboembolism" ], [ "Vein Thrombosis" ], [ "Arterial Thrombotic Occlusion" ] ], "concepts": [ "http://www.uniprot.org/uniprot/TPA_HUMAN", "http://www.biosemantics.org/jochem#4002037", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010959" ], "type": "list", "id": "52bf209303868f1b0600001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "In Japan, intravenous alteplase, a recombinant tissue-type plasminogen activator (rt-PA), was approved for an indication of ischemic stroke in 2005 on the basis of the results of a clinical trial with a unique dose of the drug (0.6 mg/kg). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23727456", "endSection": "abstract" }, { "offsetInBeginSection": 1858, "offsetInEndSection": 2051, "text": "Alteplase appears to show efficacy for treatment of thrombus-related venous catheter occlusion in pediatric patients; however, data regarding its use in occluded dialysis catheters are limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463740", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1171, "text": "The trials used to support Food and Drug Administration approval of alteplase for central venous catheter (CVC) occlusions generally had low pediatric enrollment; however, additional small studies are available that support use of alteplase for this indication in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463740", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 168, "text": "To review the literature pertaining to the efficacy of alteplase for restoration of patency of occluded venous and dialysis catheters in pediatric patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463740", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 190, "text": "Intravenous thrombolysis with recombinant tissue Plasminogen Activator improves outcomes in patients treated early after stroke but at the risk of causing intracranial hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23336348", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 309, "text": "Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23251746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1014, "text": "This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of alteplase for the treatment of acute ischaemic stroke, in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included several randomised controlled trials indicating that, in highly selected patients, alteplase administered at a licensed dose within 3 hours of the onset of acute ischaemic stroke is associated with a statistically significant reduction in the risk of death or dependency at 3 months compared with placebo, despite a significantly increased risk of symptomatic intracranial haemorrhage within the first 7-10 days. Data from the National Institute of Neurological Disorders and Stroke (NINDS) trial suggest that the benefit of treatment is sustained at 6 and 12 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19804685", "endSection": "abstract" }, { "offsetInBeginSection": 2560, "offsetInEndSection": 2837, "text": "The guidance issued by NICE in April 2007 as a result of the STA states that alteplase is recommended for the treatment of acute ischaemic stroke only when used by physicians trained and experienced in the management of acute stroke and in centres with the required facilities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19804685", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 211, "text": "Because of the risk of hemorrhage, especially in the brain, thrombolytic therapy with intravenous alteplase is restricted by guidelines, and only a small number of selected patients are being treated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17656661", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1280, "text": "Alteplase can be given to patients with cervical artery dissection, seizure at onset and evidence of acute ischemia on brain imaging, and after carefully weighing risk and benefit in pregnancy and during menstruation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17656661", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 144, "text": "Alteplase is the first thrombolytic drug to be approved in France for the treatment of ischaemic stroke within three hours of symptom onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15532135", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 376, "text": "However, the Cochrane systematic review of thrombolysis for acute ischaemic stroke suggests that alteplase is the most promising treatment for acute ischaemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12450926", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 256, "text": " To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11919252", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 370, "text": "Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11919252", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1044, "text": "Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11919252", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1760, "text": "Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11919252", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 489, "text": "Of the thrombolytic agents and therapeutic protocols in use, alteplase 100 mg/2 hours seems to be the best compromise between the risk of bleeding and efficacy in reducing pulmonary resistances by 30 to 40% and relatively early pulmonary revascularisation of 40-50%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11794977", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 230, "text": "To explore the best regimen of treatment for acute pulmonary embolism(APE), and to evaluate the efficacy and safety of 2-h infusion of recombinant tissue-type plasminogen activator, Alteplase (rt-PA) and urokinase(UK). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11778213", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1125, "text": "A 2 h regimen of rt-PA or UK showed reliable efficacy and safety for treatment of APE. The indication of thrombolytic therapy can be extended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11778213", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Tissue type plasminogen activator is available, through recombinant technology, for thrombolytic use as alteplase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772304", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 363, "text": "Alteplase has been used successfully in evolving myocardial infarction (MI) to reopen occluded coronary arteries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772304", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 760, "text": "Alteplase is most effective when given early in MI and is probably ineffective when given 12 h after the onset of symptoms. The effectiveness of alteplase in MI can be increased by front loading with a bolus of 15 mg, followed by an infusion of 50 mg over 30 min and 35 mg over 60 min.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772304", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1467, "text": "A reduced dose of alteplase to increase coronary artery patency prior to angioplasty may be useful in MI. An exciting new indication for the use of alteplase is in stroke, where it has become the first beneficial intervention. Alteplase is used to reopen occluded cerebral vessels but is associated with an increased risk of intracerebral haemorrhage. Alteplase is beneficial if given within 3 h of the onset of stroke but not after this time period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772304", "endSection": "abstract" }, { "offsetInBeginSection": 1586, "offsetInEndSection": 1813, "text": "Clinical trials have not established a role for alteplase in the treatment of acute coronary syndromes or deep vein thrombosis. However, alteplase is useful in treating pulmonary thromboembolism and peripheral vascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772304", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 277, "text": "Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9385884", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 430, "text": "Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9385884", "endSection": "abstract" }, { "offsetInBeginSection": 1912, "offsetInEndSection": 2123, "text": "The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9385884", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 1001, "text": "Alteplase is now firmly established as a treatment of choice in the management of acute myocardial infarction. The efficacy of intravenous alteplase in the treatment of pulmonary thromboembolism has also been established and appears to be similar to that of streptokinase and urokinase in this indication and in arterial thrombotic occlusion. However, its use in this latter indication and in other vascular disorders has not been as extensively documented. Although trials demonstrating the efficacy of intravenous alteplase in patients with deep vein thrombosis and intra-arterial alteplase in patients with arterial thrombotic occlusion exist, reliable data on the efficacy of the fibrinolytic in ischaemic stroke and intracranial haemorrhage are scarce.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8521760", "endSection": "abstract" }, { "offsetInBeginSection": 1756, "offsetInEndSection": 1965, "text": "Further, preliminary data suggest efficacy in the therapy of deep vein thrombosis and arterial thrombotic occlusion, and alteplase has a proven place in the fibrinolytic treatment of pulmonary thromboembolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8521760", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 527, "text": "The non-antigenic competitor for these two compounds for the indication of MI is alteplase (recombinant tissue plasminogen activator, rt-PA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7579782", "endSection": "abstract" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1270, "text": " In the framework of tailored thrombolytic therapy, alteplase or urokinase appear to be the drugs of choice in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7579782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 484, "text": "Patients with a recent (less than 10 days) proximal deep vein thrombosis of the leg or pelvis are candidates for thrombolysis as the major benefit over heparin seems to be the prevention of the postphlebitic limb, an aim which is still not proven in a satisfactory manner. Nonocclusive thrombi appear to lyse more readily than occlusive thrombi. For this indication the optimal dose regimens for the three thrombolytic drugs (streptokinase, urokinase, alteplase) are not established. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7549071", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 1301, "text": "To save 1 year of life, the costs of thrombolytic therapy using intravenous streptokinase, alteplase (recombinant tissue plasminogen activator; rt-PA) or anistreplase (anisoylated plasminogen streptokinase activator complex) under standard restricted indication criteria, vary from 1000 pounds British sterling to 1700 pounds British sterling in the UK, SEK3090 to 9660 in Scandinavia and $US35 000 to 800 000 in the US, depending on time delay in starting treatment after pain onset, size of infarct, thrombolytic agents used, study methodology, lists of clinical events considered in cost counting and the discount rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10172049", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1390, "text": "Thus, the results of the ETTT trial show that the used low dosages of alteplase administered intravenously over 3-7 days in heparinized patients cannot be recommended as a treatment for patients with deep venous thrombosis of lower limbs and/or pelvis. Further studies are needed to define a more suitable dosage regimen of alteplase in this indication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1641820", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1119, "text": "Streptokinase, urokinase and alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and pulmonary hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2689138", "endSection": "abstract" }, { "offsetInBeginSection": 1669, "offsetInEndSection": 1918, "text": "The local treatment of acute arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with streptokinase; the corresponding success rates for urokinase and alteplase are 81% and 88 to 94%, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2689138", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 241, "text": "More recently, new drugs like alteplase, reteplase, lanoteplase and saruplase have been a breakthrough in the treatment of acute myocardial infarction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581997", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 526, "text": "The non-antigenic competitor for these two compounds for the indication of MI is alteplase (recombinant tissue plasminogen activator, rt-PA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7579782", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1135, "text": "The trials used to support Food and Drug Administration approval of alteplase for central venous catheter (CVC) occlusions generally had low pediatric enrollment; however, additional small studies are available that support use of alteplase for this indication in children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463740", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 874, "text": "Some acute ischemic strokes (before the 3rd hour) could be treated with alteplase if there is no absolute or relative contraindication for thrombolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581997", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 539, "text": "Alteplase and reteplase are the most efficient thrombolytics despite a higher risk of cerebral bleeding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10581997", "endSection": "abstract" } ] }, { "body": "List scaffold proteins of the ERK signaling pathway.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23755307", "http://www.ncbi.nlm.nih.gov/pubmed/24101133", "http://www.ncbi.nlm.nih.gov/pubmed/23987506", "http://www.ncbi.nlm.nih.gov/pubmed/21615688", "http://www.ncbi.nlm.nih.gov/pubmed/17052209", "http://www.ncbi.nlm.nih.gov/pubmed/22926523", "http://www.ncbi.nlm.nih.gov/pubmed/15371409", "http://www.ncbi.nlm.nih.gov/pubmed/18823331", "http://www.ncbi.nlm.nih.gov/pubmed/24018045", "http://www.ncbi.nlm.nih.gov/pubmed/12479806", "http://www.ncbi.nlm.nih.gov/pubmed/10769183", "http://www.ncbi.nlm.nih.gov/pubmed/21401930", "http://www.ncbi.nlm.nih.gov/pubmed/23267331", "http://www.ncbi.nlm.nih.gov/pubmed/23431403", "http://www.ncbi.nlm.nih.gov/pubmed/25352726", "http://www.ncbi.nlm.nih.gov/pubmed/24278035", "http://www.ncbi.nlm.nih.gov/pubmed/17785185", "http://www.ncbi.nlm.nih.gov/pubmed/16038799", "http://www.ncbi.nlm.nih.gov/pubmed/19560418", "http://www.ncbi.nlm.nih.gov/pubmed/12133899", "http://www.ncbi.nlm.nih.gov/pubmed/21829671", "http://www.ncbi.nlm.nih.gov/pubmed/20051520", "http://www.ncbi.nlm.nih.gov/pubmed/19200235", "http://www.ncbi.nlm.nih.gov/pubmed/11940661", "http://www.ncbi.nlm.nih.gov/pubmed/15547943", "http://www.ncbi.nlm.nih.gov/pubmed/22776333", "http://www.ncbi.nlm.nih.gov/pubmed/21268275", "http://www.ncbi.nlm.nih.gov/pubmed/23763998", "http://www.ncbi.nlm.nih.gov/pubmed/15118098", "http://www.ncbi.nlm.nih.gov/pubmed/19563921", "http://www.ncbi.nlm.nih.gov/pubmed/23788642" ], "ideal_answer": [ "Originally identified in yeast, scaffold proteins are now recognized to contribute to the specificity of MEK/ERK pathways in mammalian cells. These scaffolds include kinase suppressor of Ras (KSR), beta-arrestin, MEK partner-1 (MP-1), Sef and IQ motif-containing GTPase-activating protein 1(IQGAP1). Human disc-large homolog (hDlg) acts as a MEK2-specific scaffold protein for the ERK signaling pathway. Two scaffold proteins, caveolin-1 and IQGAP1, are required for phosphorylation of the actin associated pool of extracellular signal regulated kinase 1 and 2 (ERK1/2). Several 14-3-3 isotypes bind to protein kinase C (PKC)-zeta and facilitate coupling of PKC-zeta to Raf-1 an event that boosts the mitogen-activated protein kinase (ERK) pathway.", "kinase suppressor of Ras 1\nMEK Partner 1\nBeta-arrestin\nIQ motif containing GTPase-activating protein 1\nkinase suppressor of Ras 2\nmitogen-activated protein kinase organizer 1" ], "exact_answer": [ [ "Human disc-large homolog", "hDlg" ], [ "caveolin-1" ], [ "IQ motif-containing GTPase-activating protein 1", "IQGAP1" ], [ "kinase suppressor of Ras", "KSR" ], [ "MEK partner-1", "MP-1" ], [ "beta-arrestin" ], [ "Sef" ], [ "14-3-3" ], [ "mitogen-activated protein kinase organizer 1" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032947", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070374", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097110", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004707", "http://www.uniprot.org/uniprot/EPHB2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020935" ], "type": "list", "id": "55152bd246478f2f2c000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "Human disc-large homolog (hDlg), also known as synapse-associated protein 97, is a scaffold protein, a member of the membrane-associated guanylate kinase family, implicated in neuronal synapses and epithelial-epithelial cell junctions whose expression and function remains poorly characterized in most tissues, particularly in the vasculature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615688", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 656, "text": "Using the yeast two-hybrid system to screen a human aorta cDNA library, we identified mitogen-activated protein/extracellular signal-responsive kinase (ERK) kinase (MEK)2, a member of the ERK cascade, as an hDlg binding partner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615688", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1566, "text": "Taken together, these findings allow us to hypothesize that hDlg acts as a MEK2-specific scaffold protein for the ERK signaling pathway, and may improve our understanding of how scaffold proteins, such as hDlg, differentially tune MEK1/MEK2 signaling and cell responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615688", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 468, "text": "Here, we show that two scaffold proteins, caveolin-1 and IQGAP1, are required for phosphorylation of the actin associated pool of extracellular signal regulated kinase 1 and 2 (ERK1/2) in response to protein kinase C activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23987506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "ERK activation is enhanced by the scaffolding proteins KSR and MP1, localized near the cell membrane and late endosomes respectively, but little is known about their dynamic interplay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21829671", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 942, "text": " Originally identified in yeast, scaffold proteins are now recognized to contribute to the specificity of MEK/ERK pathways in mammalian cells. These scaffolds include KSR (kinase suppressor of Ras), beta-arrestin, MEK partner-1, Sef and IQGAP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17052209", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 428, "text": "Here we analyze a potential scaffold of the Ras/mitogen-activated protein kinase (MAPK) pathway, kinase suppressor of Ras (KSR), by generating KSR-deficient mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11940661", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 865, "text": "This demonstrates that KSR is a bona fide scaffold that is not required for but enhances signaling via the Ras/MAPK signaling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11940661", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 422, "text": "We reported previously that several 14-3-3 isotypes bind to protein kinase C (PKC)-zeta and facilitate coupling of PKC-zeta to Raf-1 [van der Hoeven, van der Wal, Ruurs, van Dijk and van Blitterswijk (2000) Biochem. J. 345, 297-306], an event that boosts the mitogen-activated protein kinase (ERK) pathway in Rat-1 fibroblasts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10769183", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 567, "text": "In this study, IQGAP1 (IQ motif-containing GTPase-activating protein 1), a new Nrf2 interaction partner that we have published previously, was found to modulate MEK-ERK-mediated Nrf2 activation and induction of phase II detoxifying/antioxidant genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788642", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1118, "text": "In the aggregate, these results suggest that IQGAP1 may play an important role in the MEK-ERK-Nrf2 signaling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788642", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1566, "text": " Taken together, these findings allow us to hypothesize that hDlg acts as a MEK2-specific scaffold protein for the ERK signaling pathway, and may improve our understanding of how scaffold proteins, such as hDlg, differentially tune MEK1/MEK2 signaling and cell responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21401930", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "KSR-1 is a scaffold protein that is essential for Ras-induced activation of the highly conserved RAF-MEK-ERK kinase module. Previously, we identified a close homolog of KSR-1, called KSR-2, through structural homology-based data mining", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19563921", "endSection": "abstract" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1384, "text": "The scaffold protein beta-arrestin2 interacted with both p-ERK and D1 DA receptor, triggering the cytosolic retention of p-ERK and inducing striatal neuronal apoptotic death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19200235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Involvement of the MP1 scaffold protein in ERK signaling regulation during Drosophila wing development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18823331", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Beta-arrestin mediates desensitization and internalization of beta-adrenergic receptors (betaARs), but also acts as a scaffold protein in extracellular signal-regulated kinase (ERK) cascade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16038799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Recent studies indicate that kinase suppressor of Ras (KSR)is a scaffold protein for the Ras/Raf/MEK/ERK signaling cascade in mammals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12133899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The scaffold protein IQGAP1 regulates cell signaling through the RAF/MEK/ERK pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23763998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Kinase suppressor of Ras (KSR) is a molecular scaffold that interacts with the components of the Raf/MEK/ERK kinase cascade and positively regulates ERK signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371409", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 962, "text": "Our results indicate that KSR-2 may act as a scaffold protein similar as KSR-1 to mediate the MAPK core (RAF-MEK-ERK) signaling but with a distinct RAF isoform specificity, namely KSR-2 may only mediate the A-RAF signaling while KSR-1 is responsible for transducing signals only from c-RAF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19563921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Kinase Suppressor of Ras (KSR) is a molecular scaffold that interacts with the core kinase components of the ERK cascade, Raf, MEK, ERK to provide spatial and temporal regulation of Ras-dependent ERK cascade signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25352726", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1040, "text": "These findings identify KSR2 as a Ca2+-regulated ERK scaffold and reveal a new mechanism whereby Ca2+ impacts Ras to ERK pathway signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19560418", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 323, "text": "MEK Partner-1 (MP1) was identified as a potential \"scaffold\" protein for the mammalian extracellular signal-regulated kinase (ERK) pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15547943", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 446, "text": "The scaffold protein MP1 (MEK1 partner) assembles a scaffold complex in the ERK cascade", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12479806", "endSection": "abstract" }, { "offsetInBeginSection": 1326, "offsetInEndSection": 1534, "text": "IQGAP1 scaffold-MAP kinase (ERK) interaction was noted in the human myeloma RPMI8226 cell lines. In conclusion, IQGAP1 plays an important role in the cell proliferation of MM via the MAP kinase (ERK) pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101133", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1024, "text": "ERK-regulated, metastasis-associated scaffold protein Ezrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23755307", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 490, "text": "bsence of kinase suppressor of Ras 1 (KSR1), a scaffold protein of the ERK signaling pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23431403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "GAB2 is a scaffold protein with diverse upstream and downstream effectors. MAPK and PI3K signaling pathways are known effectors of GAB2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22926523", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 398, "text": "In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21401930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Scaffold proteins regulate intracellular MAP kinase signaling by providing critical spatial and temporal specificities. We have shown previously that the scaffold protein MEK1 partner (MP1) is localized to late endosomes by the adaptor protein p14.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21268275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The scaffold protein Shoc2/SUR-8 accelerates the interaction of Ras and Raf.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20051520", "endSection": "title" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1390, "text": "We propose that Shoc2 regulates the spatio-temporal patterns of the Ras-ERK signaling pathway primarily by accelerating the Ras-Raf interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20051520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Proteomic characterization of the dynamic KSR-2 interactome, a signaling scaffold complex in MAPK pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19563921", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 455, "text": "Kinase modules are associated with scaffold proteins that regulate signaling by providing critical spatial and temporal specificities. Some of these scaffold proteins have been shown to be conserved, both in sequence and function. In mouse, the scaffold MP1 (MEK Partner 1) forms a signaling complex with MEK1 and ERK1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18823331", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 567, "text": " extracellular signal-regulated kinase (ERK) pathway scaffold protein MP1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15118098", "endSection": "abstract" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1177, "text": "We propose that MORG1 is a component of a modular scaffold system that participates in the regulation of agonist-specific ERK signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15118098", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 792, "text": " IQGAP1, a scaffold protein linking cadherin-mediated cell adhesion to the cytoskeleton. This effect was accompanied by reduction of N-cadherin/IQGAP1/Erk-2 interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17785185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "G protein-coupled receptor kinase 2 (GRK2) is a Rho-activated scaffold protein for the ERK MAP kinase cascade.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24018045", "endSection": "title" }, { "offsetInBeginSection": 423, "offsetInEndSection": 527, "text": "GRK2 is a RhoA effector that serves as a RhoA-activated scaffold protein for the ERK MAP kinase cascade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24018045", "endSection": "abstract" } ] }, { "body": "Which are the families of mammalian DNA-(cytosine-5)-methyltransferases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21846773", "http://www.ncbi.nlm.nih.gov/pubmed/18367714", "http://www.ncbi.nlm.nih.gov/pubmed/22815530", "http://www.ncbi.nlm.nih.gov/pubmed/20838592", "http://www.ncbi.nlm.nih.gov/pubmed/23302691", "http://www.ncbi.nlm.nih.gov/pubmed/22133874", "http://www.ncbi.nlm.nih.gov/pubmed/23357425", "http://www.ncbi.nlm.nih.gov/pubmed/23393137", "http://www.ncbi.nlm.nih.gov/pubmed/21378119", "http://www.ncbi.nlm.nih.gov/pubmed/20679393", "http://www.ncbi.nlm.nih.gov/pubmed/18413740", "http://www.ncbi.nlm.nih.gov/pubmed/21559294", "http://www.ncbi.nlm.nih.gov/pubmed/17616512", "http://www.ncbi.nlm.nih.gov/pubmed/22737219", "http://www.ncbi.nlm.nih.gov/pubmed/22134929", "http://www.ncbi.nlm.nih.gov/pubmed/20071334", "http://www.ncbi.nlm.nih.gov/pubmed/22328086", "http://www.ncbi.nlm.nih.gov/pubmed/23033272", "http://www.ncbi.nlm.nih.gov/pubmed/22210859", "http://www.ncbi.nlm.nih.gov/pubmed/19173286", "http://www.ncbi.nlm.nih.gov/pubmed/19322801", "http://www.ncbi.nlm.nih.gov/pubmed/18437543", "http://www.ncbi.nlm.nih.gov/pubmed/17371843", "http://www.ncbi.nlm.nih.gov/pubmed/22140515", "http://www.ncbi.nlm.nih.gov/pubmed/17890317", "http://www.ncbi.nlm.nih.gov/pubmed/20547750", "http://www.ncbi.nlm.nih.gov/pubmed/16999741", "http://www.ncbi.nlm.nih.gov/pubmed/19626461", "http://www.ncbi.nlm.nih.gov/pubmed/22088914", "http://www.ncbi.nlm.nih.gov/pubmed/16236173", "http://www.ncbi.nlm.nih.gov/pubmed/15962389", "http://www.ncbi.nlm.nih.gov/pubmed/19576953", "http://www.ncbi.nlm.nih.gov/pubmed/19386473", "http://www.ncbi.nlm.nih.gov/pubmed/18974146", "http://www.ncbi.nlm.nih.gov/pubmed/17182866", "http://www.ncbi.nlm.nih.gov/pubmed/16575165", "http://www.ncbi.nlm.nih.gov/pubmed/17929180", "http://www.ncbi.nlm.nih.gov/pubmed/21549127", "http://www.ncbi.nlm.nih.gov/pubmed/18544619" ], "ideal_answer": [ "DNA (cytosine-5)-methyltransferases catalyze the specific transfer of a methyl group to the C5 position of cytosine residues in DNA. Three families of DNA (cytosine-5)-methyltransferases have been identified in mammals: DNMT1, DNMT2 and DNMT3 (including DNMT3a, DNMT3b and DNMT3L isoforms). All of them share homologous catalytic domains. DNMT1 is the \ufffd\ufffd\ufffdmaintenance\u201d methyltransferase family. DNMT1 is specific for hemi-methylated DNA and ensures the faithful transmission of DNA methylation patterns in every replication cycle. DNMT3 is required for de novo methylation of DNA. DNMT3 targets unmethylated DNA and is responsible for the establishment of new methylation patterns. Dnmt2, in contrast to all other mammalian DNA (cytosine-5)-methyltransferases, does not possess a large N-terminal regulatory domain. The DNA methylation activity of DNMT2 is still controversial." ], "exact_answer": [ [ "DNMT1" ], [ "DNMT2" ], [ "DNMT3" ] ], "concepts": [ "http://www.uniprot.org/uniprot/DNMT1_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248", "http://www.uniprot.org/uniprot/CMT3_MAIZE", "http://www.uniprot.org/uniprot/DNM3A_RAT", "http://www.uniprot.org/uniprot/DNMT1_ARATH", "http://www.uniprot.org/uniprot/DNM3A_CHICK", "http://www.uniprot.org/uniprot/DNM3B_MOUSE", "http://www.uniprot.org/uniprot/CMT2_MAIZE", "http://www.biosemantics.org/jochem#4250454", "http://www.uniprot.org/uniprot/CMT1_DICDI", "http://www.uniprot.org/uniprot/DCM_ECOLI", "http://www.uniprot.org/uniprot/DNM3A_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015257", "http://www.uniprot.org/uniprot/DNMT1_RAT", "http://www.uniprot.org/uniprot/DNMT1_MOUSE", "http://www.uniprot.org/uniprot/DNMT1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003596", "http://www.uniprot.org/uniprot/CMT1_MAIZE", "http://www.uniprot.org/uniprot/DNM3A_MOUSE", "http://www.uniprot.org/uniprot/DCM_ECO57", "http://www.uniprot.org/uniprot/DNMT_FRG3G", "http://www.biosemantics.org/jochem#4273977", "http://www.uniprot.org/uniprot/DNMT1_BOVIN", "http://www.uniprot.org/uniprot/DNM3B_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003886" ], "type": "list", "id": "516c3960298dcd4e51000073", "snippets": [ { "offsetInBeginSection": 449, "offsetInEndSection": 529, "text": "Of the DNMTs, DNMT1 and DNMT3a are most highly expressed in postmitotic neurons.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134929", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22133874", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Bovine DNA methylation imprints are established in an oocyte size-specific manner, which are coordinated with the expression of the DNMT3 family proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088914", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The DNMT3B de novo DNA methyltransferase (DNMT) plays a major role in establishing DNA methylation patterns in early mammalian development, but its catalytic mechanism remains poorly characterized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549127", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Dnmt2 proteins are the most conserved members of the DNA methyltransferase enzyme family, but their substrate specificity and biological functions have been a subject of controversy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20679393", "endSection": "sections.0" }, { "offsetInBeginSection": 265, "offsetInEndSection": 456, "text": "This promoter hypermethylation may be mediated not only by DNMT-1 but also by an entire family of de novo DNA-methyltransferases, such as DNA-methyltransferase-3a (DNMT-3a) and -3b (DNMT-3b).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19386473", "endSection": "sections.0" }, { "offsetInBeginSection": 114, "offsetInEndSection": 494, "text": "Within the family of DNA methyltransferases (Dnmts), Dnmt3a and 3b establish methylation marks during early development, while Dnmt1 maintains methylation patterns after DNA replication. The maintenance function of Dnmt1 is regulated by its large regulatory N-terminal domain that interacts with other chromatin factors and is essential for the recognition of hemi-methylated DNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19173286", "endSection": "sections.0" }, { "offsetInBeginSection": 166, "offsetInEndSection": 324, "text": "In this study, we examined a role for the DNA methyltransferase DNMT3B, in particular, the truncated isoform DNMT3B7, which is generated frequently in cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815530", "endSection": "sections.0" }, { "offsetInBeginSection": 741, "offsetInEndSection": 908, "text": "DNMT1 is a widely expressed DNA methyltransferase maintaining methylation patterns in development, and mediating transcriptional repression by direct binding to HDAC2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328086", "endSection": "sections.0" }, { "offsetInBeginSection": 106, "offsetInEndSection": 337, "text": "DNA methyltransferases (DNMTs) are a family of related proteins that both catalyze the de novo formation of 5-methylcytosine and maintain these methylation marks in cell-specific patterns in virtually all mitotic cells of the body.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134929", "endSection": "sections.0" }, { "offsetInBeginSection": 209, "offsetInEndSection": 340, "text": "This methylation is critical for imprinting; a reduction in the DNA methyltransferase DNMT1 causes a widespread loss of imprinting.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20547750", "endSection": "sections.0" }, { "offsetInBeginSection": 124, "offsetInEndSection": 218, "text": "DNA methyltransferase 3B (DNMT3B) is the key methyltransferase in DNA methylation regulations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576953", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "DNA methyltransferases (DNMTs) are a family of enzymes that methylate DNA at the C5 position of cytosine residues, and their inhibition is a promising strategy for the treatment of various developmental and proliferative diseases, particularly cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19322801", "endSection": "sections.0" }, { "offsetInBeginSection": 137, "offsetInEndSection": 203, "text": "DNA methylation is mediated by a family of DNA methyltransferases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18437543", "endSection": "sections.0" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1357, "text": "These results suggest that DNMT1 and DNMT3B regulate BAG-1 expression via insulator protein DNA-binding and chromatin dynamics by regulating histone dimethylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18413740", "endSection": "sections.0" }, { "offsetInBeginSection": 336, "offsetInEndSection": 468, "text": "Here we show that human miR-148 represses DNA methyltransferase 3b (Dnmt3b) gene expression through a region in its coding sequence.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18367714", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) including the maintenance enzyme DNMT 1 and de novo methyltransferases DNMT 3a and DNMT 3b.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17929180", "endSection": "sections.0" }, { "offsetInBeginSection": 325, "offsetInEndSection": 676, "text": "Among the reported down-regulated miRNAs in lung cancer, the miRNA (miR)-29 family (29a, 29b, and 29c) has intriguing complementarities to the 3'-UTRs of DNA methyltransferase (DNMT)3A and -3B (de novo methyltransferases), two key enzymes involved in DNA methylation, that are frequently up-regulated in lung cancer and associated with poor prognosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17890317", "endSection": "sections.0" }, { "offsetInBeginSection": 658, "offsetInEndSection": 797, "text": "Furthermore, we have examined the roles of the de novo methyltransferases (Dnmt3a and Dnmt3b) and related protein (Dnmt3L) in this process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17616512", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "DNA methyltransferase 1 (DNMT1) has been reported to interact with a wide variety of factors and to contain intrinsic transcriptional repressor activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17371843", "endSection": "sections.0" }, { "offsetInBeginSection": 462, "offsetInEndSection": 690, "text": "Inactivation of both Dnmt3a and Dnmt3b, DNA methyltransferases essential for the initiation of de novo DNA methylation, abolished the establishment of DNA methylation and the silencing of Rhox cluster genes in the embryo proper.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17182866", "endSection": "sections.0" }, { "offsetInBeginSection": 411, "offsetInEndSection": 553, "text": "Rather, in vitro analysis indicates that Dnmt3L stimulates DNA methylation by both Dnmt3a and Dnmt3b through direct binding to these proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16999741", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "OBJECTIVE: To investigate the association between single nucleotide polymorphism (SNP) in promoter of the DNA methyltransferase 3B (DNMT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15962389", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Methylation at the 5-position of DNA cytosine on the vertebrate genomes is accomplished by the combined catalytic actions of three DNA methyltransferases (DNMTs), the de novo enzymes DNMT3A and DNMT3B and the maintenance enzyme DNMT1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393137", "endSection": "sections.0" }, { "offsetInBeginSection": 221, "offsetInEndSection": 303, "text": "There are two major categories of DNA methyltransferases: de novo and maintenance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357425", "endSection": "sections.0" }, { "offsetInBeginSection": 274, "offsetInEndSection": 366, "text": "Some, but not all, murine H1 subtypes interact with DNA methyltransferases DNMT1 and DNMT3B.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23302691", "endSection": "sections.0" } ] }, { "body": "Which classes of endogenous retroelements are known to date?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22406018", "http://www.ncbi.nlm.nih.gov/pubmed/18636276", "http://www.ncbi.nlm.nih.gov/pubmed/10697412" ], "ideal_answer": [ "Endogenous retroelements fall into two distinct classes: retrotransposons containing LTRs (Long Terminal Repeats), and retrostransposons lacking LTRs." ], "exact_answer": [ [ "retrotransposons containing LTRs (Long Terminal Repeats)" ], [ "retrostransposons lacking LTRs (Long Terminal Repeats)" ] ], "type": "list", "id": "54e0ac041388e8454a00000f", "snippets": [ { "offsetInBeginSection": 135, "offsetInEndSection": 427, "text": "Transposons are divided into two general classes based on their transposition intermediate (DNA or RNA). Only one subclass, the non-LTR retrotransposons, which includes the Long INterspersed Element-1 (LINE-1 or L1), is currently active in humans as indicated by 96 disease-causing insertions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Diversity of LTR-retrotransposons and Enhancer/Suppressor Mutator-like transposons in cassava", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18636276", "endSection": "title" }, { "offsetInBeginSection": 484, "offsetInEndSection": 659, "text": "Members of two classes of LTR-retrotransposons, Ty1/copia-like and Ty3/gypsy-like, and of Enhancer/Suppressor Mutator (En/Spm)-like transposons were isolated and characterised", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18636276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Mammalian LINE-1 (L1) elements belong to the superfamily of autonomously replicating retrotransposable elements that lack the long terminal repeated (LTR) sequences typical of retroviruses and retroviral-like retrotransposons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10697412", "endSection": "abstract" } ] }, { "body": "What is the association between proBNP serum concentrations and stroke outcomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23701638", "http://www.ncbi.nlm.nih.gov/pubmed/25102374", "http://www.ncbi.nlm.nih.gov/pubmed/16565563", "http://www.ncbi.nlm.nih.gov/pubmed/17904063" ], "ideal_answer": [ "ProBNP serum concentrations are elevated in stroke patients relative to healthy controls. Greater proBNP serum concentrations are associated with greater stroke severity and with increased risk for unfvorable functional outcomes." ], "type": "summary", "id": "54e1c5d5ae9738404b00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "N-terminal probrain natriuretic peptide levels as a predictor of functional outcomes in patients with ischemic stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102374", "endSection": "title" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1865, "text": "There was a strong positive correlation between the plasma level of NT-proBNP and the National Institutes of Health Stroke Scale score (r=0.415, P=0.000). Plasma levels of NT-proBNP in patients with an unfavorable outcome were significantly higher than those in patients with a favorable outcome [3432 (interquartile range, 1100-54991) vs. 978 (interquartile range, 123-1705) pg/ml; P=0.000]. In multivariate analyses, after adjusting for all other significant outcome predictors, the NT-proBNP level that remained can be seen as an independent unfavorable outcome predictor, with an adjusted odds ratios of 4.14 (95% confidence interval, 2.72-7.99; P=0.000). Our results show that plasma NT-proBNP levels were significantly elevated in patients with an unfavorable outcome and might be of clinical importance as a supplementary tool for the assessment of functional outcomes in patients with AIS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102374", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 1389, "text": "Plasma levels of BNP, NT-proBNP, cortisol and copeptin were associated with stroke severity, as well as short-term functional outcomes. After adjusting for all other significant outcome predictors, NT-proBNP, cortisol and copeptin remained as independent outcome predictors. In the receiver operating characteristic curve analysis, the biomarker panel (including BNP, NT-proBNP, cortisol and copeptin) predicted functional outcome and death within 90 days significantly more efficiently than the National Institute of Health Stroke Scale (NIHSS) or the biomarker alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23701638", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 798, "text": "The NT-proBNP levels were significantly higher at 4 intervals after ischemic stroke than in healthy and at-risk control subjects (all p<0.001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16565563", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1742, "text": "Multivariate analysis demonstrated that age and NIH Stroke Scale were the 2 strongest independent predictors of increased NT-proBNP levels (all p<0.01). Furthermore, increased NT-proBNP (> or = 150 pg/ml) was the strongest independent predictor of long-term (mean follow-up: 24 months) UFCO (26 patients) (all p<0.05). CONCLUSIONS: The NT-proBNP level was markedly elevated after acute ischemic stroke and declined substantially thereafter. An increased NT-proBNP level was strongly and independently correlated with UFCO in patients after ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16565563", "endSection": "abstract" } ] }, { "body": "What is the effect that EZH2 has on chromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19026781", "http://www.ncbi.nlm.nih.gov/pubmed/18980972", "http://www.ncbi.nlm.nih.gov/pubmed/24040281", "http://www.ncbi.nlm.nih.gov/pubmed/20631058", "http://www.ncbi.nlm.nih.gov/pubmed/19954516", "http://www.ncbi.nlm.nih.gov/pubmed/22821416", "http://www.ncbi.nlm.nih.gov/pubmed/22966008", "http://www.ncbi.nlm.nih.gov/pubmed/25617436", "http://www.ncbi.nlm.nih.gov/pubmed/15520282", "http://www.ncbi.nlm.nih.gov/pubmed/24077602", "http://www.ncbi.nlm.nih.gov/pubmed/9214638", "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "http://www.ncbi.nlm.nih.gov/pubmed/21892963", "http://www.ncbi.nlm.nih.gov/pubmed/23688634" ], "ideal_answer": [ "Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms", "Ez that catalyzes di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription. The mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles. PRC2-Ezh2 catalyzes H3K27me2/3 and its knockdown affects global H3K27me2/3 levels. EZH2 thus maintains chromatin in a repressive state." ], "concepts": [ "http://www.uniprot.org/uniprot/EZH2_HUMAN", "http://www.uniprot.org/uniprot/EZH2A_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002843", "http://www.uniprot.org/uniprot/EZH2_MOUSE", "http://amigo.geneontology.org/amigo/term/GO:0000785", "http://www.uniprot.org/uniprot/EZH2_XENTR", "http://www.uniprot.org/uniprot/EZH2_DANRE", "http://www.uniprot.org/uniprot/EZH2_MACFA", "http://www.uniprot.org/uniprot/EZH2B_XENLA" ], "type": "summary", "id": "570906fecf1c325851000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026781", "endSection": "title" }, { "offsetInBeginSection": 164, "offsetInEndSection": 399, "text": "Ez that catalyzes di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription. We report that the mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026781", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1185, "text": "During progenitor cell differentiation and ageing, PcG silencer EZH2 attenuates, causing loss of PRC binding and transcriptional activation of INK4b and INK4a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19954516", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 780, "text": "the PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21892963", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 564, "text": "In this study, we found the inverse correlation between FOXP3 and Ezh2, an enzyme for histone H3K27 trimethylation (H3K27me3) and a central epigenetic regulator in cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "title" }, { "offsetInBeginSection": 291, "offsetInEndSection": 427, "text": "CD28 co-stimulation, an extracellular cue intrinsically required for Treg cell maintenance, induced the chromatin-modifying enzyme, Ezh2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 617, "text": "Treg-specific ablation of Ezh2 resulted in spontaneous autoimmunity with reduced Foxp3(+) cells in non-lymphoid tissues and impaired resolution of experimental autoimmune encephalomyelitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "abstract" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1120, "text": "These studies reveal a critical role for Ezh2 in the maintenance of Treg cell identity during cellular activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1037, "text": "We assessed the effect of efficient RNA interference-mediated knockdown of EZH2 on RUNX3 levels, cell viability and H3K27 trimethylation of the RUNX3 promoter using chromatin immunoprecipitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20631058", "endSection": "abstract" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1960, "text": "We found that siRNAs Ezh2 and post-transcriptional silencing of Ezh2 by let-7 g rescued this effect suggesting that Ezh2 up-regulation is in part responsible for increased H3K27me3 and decreased rates of up-regulation of differentiation genes in Dicer(-/-)ES.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Enhancer of zeste homologue 2 (EZH2), a histone methyltransferase, plays a key role in transcriptional repression through chromatin remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18980972", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1339, "text": "Chromatin immunoprecipitation analysis revealed binding of EZH2 at the p57kip2 promoter and reduction of histone H3K27 trimethylation upon gene suppression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821416", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1490, "text": "The E(z) gene family reveals a striking functional conservation in mediating gene repression in eukaryotic chromatin: extra gene copies of human EZH2 or Drosophila E(z) in transgenic flies enhance position effect variegation of the heterochromatin-associated white gene, and expression of either human EZH2 or murine Ezh1 restores gene repression in Saccharomyces cerevisiae mutants that are impaired in telomeric silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9214638", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1228, "text": "The authors further showed that forced expression of SAFB1 increases H3K27me3 at AR target loci and this effect requires EZH2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24077602", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 847, "text": "We assessed the effect of efficient RNA interference-mediated knockdown of EZH2 on RUNX3 levels, cell viability and H3K27 trimethylation of the RUNX3 promoter using chromatin immunoprecipitation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20631058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Enhancer of zeste homologue 2 (EZH2), a histone methyltransferase, plays a key role in transcriptional repression through chromatin remodeling. Our objectives were to determine the expression pattern of EZH2 and to assess the anticancer effect of EZH2 depletion in pancreatic cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18980972", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 847, "text": "We assessed the effect of efficient RNA interference-mediated knockdown of EZH2 on RUNX3 levels, cell viability and H3K27 trimethylation of the RUNX3 promoter using chromatin immunoprecipitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20631058", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1165, "text": "EZH2 interacts directly with Snail2, and Snail2 fails to expand the neural crest domains in the absence of Ezh2. Chromatin immunoprecipitation analysis shows that Snail2 regulates EZH2 occupancy and histone H3K27 trimethylation levels at the promoter region of the Snail2 target E-cadherin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25617436", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1123, "text": "To identify direct target genes of Ezh2, we performed chromatin immunoprecipitation experiments followed by whole-genome promoter arrays (chromatin immunoprecipitation-on-chip) and identified 5585 genes associated with trimethylation of lysine 27 in histone 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22966008", "endSection": "abstract" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1191, "text": "Chromatin immunoprecipitation analysis revealed binding of EZH2 at the p57kip2 promoter and reduction of histone H3K27 trimethylation upon gene suppression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821416", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 973, "text": "YY1 was required for Ezh2 binding because RNA interference of YY1 abrogated chromatin recruitment of Ezh2 and prevented H3-K27 methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520282", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1165, "text": "Chromatin immunoprecipitation analysis shows that Snail2 regulates EZH2 occupancy and histone H3K27 trimethylation levels at the promoter region of the Snail2 target E-cadherin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25617436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026781", "endSection": "title" } ] }, { "body": "Does Chromatin Immunoprecipitation (ChIP) show a bias for highly expressed loci?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24173036", "http://www.ncbi.nlm.nih.gov/pubmed/17477493", "http://www.ncbi.nlm.nih.gov/pubmed/22248020", "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "http://www.ncbi.nlm.nih.gov/pubmed/24255646", "http://www.ncbi.nlm.nih.gov/pubmed/21934668", "http://www.ncbi.nlm.nih.gov/pubmed/22499706", "http://www.ncbi.nlm.nih.gov/pubmed/17592629", "http://www.ncbi.nlm.nih.gov/pubmed/22522655", "http://www.ncbi.nlm.nih.gov/pubmed/21554688" ], "ideal_answer": [ "Several issues in the processing and analysis of ChIP-chip data have not been resolved fully, including the effect of background (mock control) subtraction and normalization within and across arrays. We detected a chromatin-state bias: open chromatin regions yielded higher coverage, which led to false positives if not corrected. The localization of unrelated proteins, including the entire silencing complex, to the most highly transcribed genes was highly suggestive of a technical issue with the immunoprecipitations." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020224", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047369" ], "type": "yesno", "id": "52ef6da1c8da898910000011", "snippets": [ { "offsetInBeginSection": 179, "offsetInEndSection": 386, "text": "However, several issues in the processing and analysis of ChIP-chip data have not been resolved fully, including the effect of background (mock control) subtraction and normalization within and across arrays", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17592629", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1695, "text": " Proper normalization is essential for ChIP-chip experiments. The proposed normalization technique can correct systematic errors and compensate for the lack of mock control data, thus reducing the experimental cost and producing more accurate results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17592629", "endSection": "abstract" }, { "offsetInBeginSection": 930, "offsetInEndSection": 1164, "text": "Subtraction of the mock (non-specific antibody or no antibody) control data is generally needed to eliminate the bias, but appropriate normalization obviates the need for mock experiments and increases the correlation among replicates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17592629", "endSection": "abstract" }, { "offsetInBeginSection": 1718, "offsetInEndSection": 1839, "text": "The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22248020", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 263, "text": "However, the data generated will always contain noise due to e.g. repetitive regions or non-specific antibody interactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22248020", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 466, "text": "The generation of high copy numbers of DNA fragments as an artifact of the PCR step in ChIP-seq is an important source of bias of this methodology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554688", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 671, "text": "Here we describe several technical aspects of the ChIP-Seq assay that diminish bias and background noise and allow the consistent generation of high-quality data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21934668", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 838, "text": " This theoretical paper systematically characterizes the biases and properties of ChIP-seq data by comparing 62 separate publicly available datasets, using rigorous statistical models and signal processing techniques", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22499706", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 470, "text": "We detected a chromatin-state bias: open chromatin regions yielded higher coverage, which led to false positives if not corrected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522655", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 558, "text": "This bias had a greater effect on detection specificity than any base-composition bias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522655", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 442, "text": "This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 787, "text": "We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 498, "text": "We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24255646", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 938, "text": "The 238 loci, termed \"hyper-ChIPable\", were in highly expressed regions with strong polymerase II and polymerase III enrichment signals, and the correlation between transcription level and ChIP enrichment was not limited to these 238 loci but extended genome-wide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24173036", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1311, "text": "The localization of unrelated proteins, including the entire silencing complex, to the most highly transcribed genes was highly suggestive of a technical issue with the immunoprecipitations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24173036", "endSection": "abstract" } ] }, { "body": "Is clathrin involved in E-cadherin endocytosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17298950", "http://www.ncbi.nlm.nih.gov/pubmed/12657640", "http://www.ncbi.nlm.nih.gov/pubmed/23671930", "http://www.ncbi.nlm.nih.gov/pubmed/18331728", "http://www.ncbi.nlm.nih.gov/pubmed/21516109" ], "ideal_answer": [ "E-cadherin is a central component of the adherens junction in epithelial cells and continuously undergoes endocytosis via clathrin-coated vesicles and/or caveolae depending on the cell type." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006897", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004705", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0072583", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030100", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000369", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015820", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071439", "http://www.uniprot.org/uniprot/CADH1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002966" ], "type": "yesno", "id": "5319ac18b166e2b806000030", "snippets": [ { "offsetInBeginSection": 1024, "offsetInEndSection": 1315, "text": "We demonstrated that GnT-III induced a stabilizing effect on E-cadherin at the cell membrane by inducing a delay in the turnover rate of the protein, contributing for the formation of stable and functional adherens-junctions, and further preventing clathrin-dependent E-cadherin endocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23671930", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1479, "text": "Conversely, GnT-V promotes the destabilization of E-cadherin, leading to its mislocalization and unstable adherens-junctions with impairment of cell-cell adhesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23671930", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 561, "text": "Here we show that E-cadherin polarity is controlled by the polarized regulation of clathrin- and dynamin-mediated endocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21516109", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 786, "text": "We delineate a pathway that controls the initiation of E-cadherin endocytosis through the regulation of AP2 and clathrin coat recruitment by E-cadherin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21516109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Clathrin dependent endocytosis of E-cadherin is regulated by the Arf6GAP isoform SMAP1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18331728", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "E-cadherin is a central component of the adherens junction in epithelial cells and continuously undergoes endocytosis via clathrin-coated vesicles and/or caveolae depending on the cell type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18331728", "endSection": "abstract" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1471, "text": "Collectively, SMAP1 likely represents a key Arf6GAP in clathrin dependent endocytosis of E-cadherin in MDCK cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18331728", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 860, "text": "Consistent with these observations, we found that selective uncoupling of p120 from E-cadherin by introduction of amino acid substitutions in the p120-binding site increased the level of E-cadherin endocytosis. The increased endocytosis was clathrin-dependent, because it was blocked by expression of a dominant-negative form of dynamin or by hypertonic shock.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17298950", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 725, "text": "We found that in this experimental system E-cadherin entered a transferrin-negative compartment before transport to the early endosomal compartment, where it merged with classical clathrin-mediated uptake pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12657640", "endSection": "abstract" } ] }, { "body": "What are the generic versions of Viagra", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21054594", "http://www.ncbi.nlm.nih.gov/pubmed/22386826", "http://www.ncbi.nlm.nih.gov/pubmed/21591526" ], "ideal_answer": [ "Sildenafil Citrate and Elonza in Thailand are the generic versions of Viagra" ], "concepts": [ "http://www.biosemantics.org/jochem#4266960" ], "type": "summary", "id": "5150b1f4d24251bc0500006a", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 36, "text": "Sildenafil citrate (SIL)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22386826", "endSection": "sections.0" }, { "offsetInBeginSection": 242, "offsetInEndSection": 470, "text": "generic sildenafil (Unison Laboratories, Thailand) was proved to have the same bioequivalent as in the original formula. The authors conducted a 12-week case series to study the efficacy and safety of Elonza (generic sildenafil)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21591526", "endSection": "sections.0" }, { "offsetInBeginSection": 227, "offsetInEndSection": 291, "text": "Viagra tablets or generic versions containing sildenafil citrate", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21054594", "endSection": "sections.0" } ] }, { "body": "List GATA-1 interacting partners as discovered with the help of the biotinylation tagging approach.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "http://www.ncbi.nlm.nih.gov/pubmed/16888367", "http://www.ncbi.nlm.nih.gov/pubmed/19196479" ], "ideal_answer": [ "Our work describes, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes", "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes ", "The biotinylation tagging approach revealed, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes." ], "exact_answer": [ [ "Gfi-1b" ], [ "MeCP1 complex" ], [ "ACF/WCRF complex" ], [ "fog-1" ], [ "tal-1" ] ], "type": "list", "id": "553a7a59f321868558000002", "snippets": [ { "offsetInBeginSection": 752, "offsetInEndSection": 1010, "text": "Our work describes, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1302, "text": "We also provide evidence that distinct GATA-1 complexes are associated with specific GATA-1 functions in erythroid differentiation, for example, GATA-1/Gfi-1b with the suppression of cell proliferation and GATA-1/FOG-1/MeCP1 with the repression of other hematopoietic transcription programs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1517, "text": "We next applied the biotinylation tag to Ldb-1, a known partner of GATA-1, and characterized a number of novel interaction partners that are essential in erythroid development, in particular, Eto-2, Lmo4, and CdK9", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 664, "text": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 1015, "text": " Importantly, we show that FOG-1 mediates GATA-1 interactions with the MeCP1 complex, thus providing an explanation for the overlapping functions of these two factors in erythropoiesis. We also show that subsets of GATA-1 gene targets are bound in vivo by distinct complexes, thus linking specific GATA-1 partners to distinct aspects of its functions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 663, "text": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 665, "text": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1303, "text": "We also provide evidence that distinct GATA-1 complexes are associated with specific GATA-1 functions in erythroid differentiation, for example, GATA-1/Gfi-1b with the suppression of cell proliferation and GATA-1/FOG-1/MeCP1 with the repression of other hematopoietic transcription programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 1011, "text": "Our work describes, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "abstract" } ] }, { "body": "Which diseases are associated with Alu element insertion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7874122", "http://www.ncbi.nlm.nih.gov/pubmed/22723857", "http://www.ncbi.nlm.nih.gov/pubmed/17146684", "http://www.ncbi.nlm.nih.gov/pubmed/20157369", "http://www.ncbi.nlm.nih.gov/pubmed/15841484", "http://www.ncbi.nlm.nih.gov/pubmed/17178205" ], "ideal_answer": [ "Diseases associated with Alu element insertion are the following: myotonic dystrophy type 2, Friedreich ataxia, spinocerebellar ataxia type 10, autosomal dominant optic atrophy, Menkes disease, hyper-IgM with immunodeficiency syndrome (HIGM), and anterior pituitary aplasia." ], "exact_answer": [ [ "myotonic dystrophy type 2" ], [ "Friedreich ataxia" ], [ "spinocerebellar ataxia type 10" ], [ "autosomal dominant optic atrophy" ], [ "Menkes disease" ], [ "hyper-IgM with immunodeficiency syndrome (HIGM)" ], [ "anterior pituitary aplasia" ], [ "HNPCC" ], [ "FAP" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004251", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020087" ], "type": "list", "id": "52f129d92059c6d71c000009", "snippets": [ { "offsetInBeginSection": 1254, "offsetInEndSection": 1427, "text": "Alu elements are known to be the source of microsatellite repeats responsible for two other repeat expansion disorders: Friedreich ataxia and spinocerebellar ataxia type 10.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723857", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 891, "text": "We identified an Alu-element insertion located in intron 7 of OPA1 causing an in-frame deletion of exon 8 in 18 family members.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20157369", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 159, "text": "Autosomal dominant optic atrophy (ADOA) is the most common form of hereditary optic neuropathy caused by mutations in the optic atrophy 1 (OPA1) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20157369", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1206, "text": "However, this is the first report of a pathogenic OPA1 gene mutation resulting from an Alu insertion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20157369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The first reported case of Menkes disease caused by an Alu insertion mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17178205", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "We present the first reported case of Menkes disease caused by an Alu element insertion mutation that interfered with splicing regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17178205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "HIGM syndrome caused by insertion of an AluYb8 element in exon 1 of the CD40LG gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17146684", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "A new mutation of the CD40LG gene that encodes the CD40 ligand molecule was characterized in a young patient harboring a hyper-IgM with immunodeficiency syndrome. Inactivation of CD40LG gene resulted from the insertion of an AluYb8 element in exon 1 responsible for a total deficiency of CD40 ligand expression by T lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17146684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Alu-element insertion in the homeodomain of HESX1 and aplasia of the anterior pituitary", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15841484", "endSection": "title" }, { "offsetInBeginSection": 697, "offsetInEndSection": 875, "text": "One patient, who also has retinal coloboma, carries a HESX1 defect in the homozygous state: an Alu insertion in exon 3, a sequence that encodes the major part of the homeodomain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15841484", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1334, "text": "Anterior pituitary aplasia is a new example of a human disease caused by a germline retrotransposition event involving an Alu sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15841484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Myotonic dystrophy (DM) is associated with abnormal expansions of the CTG repeats in the 3' untranslated region of its gene. Previous studies in individuals of European origin demonstrated strong linkage disequilibrium between different CTG repeat length alleles and an Alu element insertion/deletion polymorphism in intron 8 of the DM gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7874122", "endSection": "abstract" } ] }, { "body": "Approximately how many recombination hotspots have been found in the yeast genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18449558", "http://www.ncbi.nlm.nih.gov/pubmed/8290959", "http://www.ncbi.nlm.nih.gov/pubmed/17478517", "http://www.ncbi.nlm.nih.gov/pubmed/16640774", "http://www.ncbi.nlm.nih.gov/pubmed/18682829", "http://www.ncbi.nlm.nih.gov/pubmed/19557188" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0010844", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0003677" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0003677", "o": "DNA binding" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0010844", "o": "DNA binding, recombination hotspot" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0010844", "o": "recombination hotspot binding" }, { "p": "http://www.w3.org/2004/02/skos/core#relatedSynonym", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0003677", "o": "microtubule/chromatin interaction" }, { "p": "http://www.w3.org/2004/02/skos/core#narrowSynonym", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0003677", "o": "plasmid binding" } ], "ideal_answer": [ "In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs." ], "exact_answer": [ "Approximately 200", "200", "~200" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015003", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006312", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010844", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012441", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051598", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011995", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ], "type": "factoid", "id": "534e364e288f4dae47000001", "snippets": [ { "offsetInBeginSection": 387, "offsetInEndSection": 536, "text": "In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18682829", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 385, "text": "Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18682829", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 214, "text": "meiotic recombination is initiated by double-strand DNA breaks (DSBs) which occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17478517", "endSection": "abstract" } ] }, { "body": "How could iPSCs be used for the treatment of diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24035588", "http://www.ncbi.nlm.nih.gov/pubmed/21060967", "http://www.ncbi.nlm.nih.gov/pubmed/25479728", "http://www.ncbi.nlm.nih.gov/pubmed/24794627", "http://www.ncbi.nlm.nih.gov/pubmed/23197849", "http://www.ncbi.nlm.nih.gov/pubmed/21464439", "http://www.ncbi.nlm.nih.gov/pubmed/21755313", "http://www.ncbi.nlm.nih.gov/pubmed/24577791", "http://www.ncbi.nlm.nih.gov/pubmed/22512788", "http://www.ncbi.nlm.nih.gov/pubmed/25059784", "http://www.ncbi.nlm.nih.gov/pubmed/24469711", "http://www.ncbi.nlm.nih.gov/pubmed/24784583", "http://www.ncbi.nlm.nih.gov/pubmed/24911883", "http://www.ncbi.nlm.nih.gov/pubmed/24554704", "http://www.ncbi.nlm.nih.gov/pubmed/22820846" ], "ideal_answer": [ "One of the promising approaches to cure diabetes is to use induced PCSs (iPSCs) and to differentiate them into insulin-secreting \u03b2 cells. The induction of iPSC differentiation into insulin-secreting cells can be achieved in several ways, such as with the use of microRNAs, or adenoviral transfection with selected genes." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048909", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016640", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003921" ], "type": "summary", "id": "56f55cc809dd18d46b000008", "snippets": [ { "offsetInBeginSection": 96, "offsetInEndSection": 284, "text": "Human induced pluripotent stem cells (hiPSCs) have raised the possibility that patient-specific insulin-secreting cells might be derived from somatic cells through cell fate reprogramming.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24469711", "endSection": "abstract" }, { "offsetInBeginSection": 1487, "offsetInEndSection": 1608, "text": "We demonstrated for the first time that miRNAs might be ideal substitutes to induce pancreatic differentiation in hiPSCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24469711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Pluripotent stem cells as a potential tool for disease modelling and cell therapy in diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24577791", "endSection": "title" }, { "offsetInBeginSection": 210, "offsetInEndSection": 533, "text": "One of the promising approaches to understand and cure diabetes is to use pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs). ESCs and iPSCs have a great potential to differentiate into all cell types, and they have a high ability to differentiate into insulin-secreting \u03b2 cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24577791", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1431, "text": "Several iPSC lines have been recently generated from patients with different types of diabetes, and most of these cell lines are able to differentiate into insulin-secreting \u03b2 cells. In this review, we summarize recent advances in the differentiation of pancreatic \u03b2 cells from PSCs, and describe the challenges for their clinical use in diabetes cell therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24577791", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 396, "text": "The aim of this study was to evaluate the effect of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) in the differentiation of induced pluripotent stem cells (iPSCs) into insulin-producing cells and to explore this new approach of cell transplantation therapy for type 1 diabetes in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794627", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 584, "text": " iPSCs were infected with adenovirus (Ad-Mouse PDX-1-IRES-GFP, Ad-Mouse NeuroD1-IRES-GFP and Ad-Mouse Mafa-IRES-GFP) and then differentiated into insulin-producing cells in vitro. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794627", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1696, "text": "The insulin-producing cells we obtained from three-gene-modified EBs may be used as seed cells for tissue engineering and may represent a cell replacement strategy for the production of \u03b2 cells for the treatment of type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794627", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 379, "text": "To date, the pathogenesis of diabetes is far to be understood, and there is no permanent treatment available for diabetes. One of the promising approaches to understand and cure diabetes is to use pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PCSs (iPSCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24577791", "endSection": "abstract" } ] }, { "body": "What is the name of the stem loop present in the 3' end of genes encoding for selenoproteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19467292", "http://www.ncbi.nlm.nih.gov/pubmed/11092556", "http://www.ncbi.nlm.nih.gov/pubmed/17470795", "http://www.ncbi.nlm.nih.gov/pubmed/8344267", "http://www.ncbi.nlm.nih.gov/pubmed/24251578", "http://www.ncbi.nlm.nih.gov/pubmed/8601283", "http://www.ncbi.nlm.nih.gov/pubmed/23788723", "http://www.ncbi.nlm.nih.gov/pubmed/8955902", "http://www.ncbi.nlm.nih.gov/pubmed/11839807", "http://www.ncbi.nlm.nih.gov/pubmed/17715293", "http://www.ncbi.nlm.nih.gov/pubmed/23603359", "http://www.ncbi.nlm.nih.gov/pubmed/23783574", "http://www.ncbi.nlm.nih.gov/pubmed/10334333", "http://www.ncbi.nlm.nih.gov/pubmed/9256076", "http://www.ncbi.nlm.nih.gov/pubmed/15791204", "http://www.ncbi.nlm.nih.gov/pubmed/22209284", "http://www.ncbi.nlm.nih.gov/pubmed/17901054", "http://www.ncbi.nlm.nih.gov/pubmed/8602359", "http://www.ncbi.nlm.nih.gov/pubmed/23614019", "http://www.ncbi.nlm.nih.gov/pubmed/8634917", "http://www.ncbi.nlm.nih.gov/pubmed/19179357", "http://www.ncbi.nlm.nih.gov/pubmed/20385601", "http://www.ncbi.nlm.nih.gov/pubmed/10567350" ], "ideal_answer": [ "SECIS (selenocysteine insertion sequence)" ], "exact_answer": [ "SECIS" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055029", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051149", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035613", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051150", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051151", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051140" ], "type": "factoid", "id": "533ea8fcc45e133714000010", "snippets": [ { "offsetInBeginSection": 343, "offsetInEndSection": 419, "text": "stem-loop structure called the selenocysteine incorporating sequence (SECIS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251578", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 270, "text": "3'-UTR mRNA stem-loop termed SElenoCysteine Insertion Sequence (SECIS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788723", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 194, "text": "Sec is inserted by a specific translational machinery that recognizes a stem-loop structure, the SECIS element", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23783574", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 509, "text": "Selenocysteine Insertion Sequence (SECIS) element in the 3'UTR of the transcript.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23614019", "endSection": "abstract" }, { "offsetInBeginSection": 1394, "offsetInEndSection": 1440, "text": "The proximal stem-loop promotes Sec insertion ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23614019", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 379, "text": "Selenocysteine is encoded by an in-frame UGA codon specified by a stem-loop structure, the Sec insertion sequence element (SECIS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603359", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 577, "text": "3' untranslated region RNA stem loop called a SEC incorporation sequence (SECIS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22209284", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 424, "text": "recoding of UGA as Sec depends on the selenocysteine insertion sequence (SECIS) element, a stem-loop structure in the 3' untranslated region of the transcript", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385601", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 223, "text": "this requires a dedicated machinery comprising a stem-loop structure in the 3' UTR RNA (the SECIS element)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19467292", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 306, "text": "RNA stem-loop structure, the SECIS element in the 3 untranslated region of (UTR) selenoprotein mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19179357", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 248, "text": "recoding of the UGA stop codon to selenocysteine. In eukaryotes, this requires an RNA stem loop structure in the 3'-untranslated region, termed a selenocysteine insertion sequence (SECIS),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17901054", "endSection": "abstract" }, { "offsetInBeginSection": 23, "offsetInEndSection": 198, "text": " insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stem-loop structure known as Sec insertion sequence (SECIS) element", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17715293", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 295, "text": "In eukaryotes, incorporation of Sec requires a Sec insertion sequence (SECIS) element, a stem-loop structure located in the 3'-untranslated regions of selenoprotein mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17470795", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 327, "text": "selenocysteine insertion requires a cis-acting selenocysteine insertion sequence (SECIS) usually located in the 3'UTR of selenoprotein mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15791204", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 234, "text": "The Sec insertion sequence (SECIS) element, which is the stem-loop structure present in 3' untranslated regions (UTRs) of eukaryotic selenoprotein-encoding genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11839807", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 534, "text": "For eukaryotic selenoprotein mRNAs, it has been proposed that a conserved stem-loop structure designated the Sec insertion sequence (SECIS) in the 3'-untranslated (3'-UTR) region is required for recognition of UGA as a Sec codon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11092556", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 379, "text": "3'-untranslated regions of selenoprotein genes contain a common stem-loop structure, selenocysteine insertion sequence (SECIS) element, that is necessary for decoding UGA as selenocysteine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10567350", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 566, "text": "Analyses of eukaryotic selenocysteine insertion sequence (SECIS) elements via computer folding programs, mutagenesis studies, and chemical and enzymatic probing has led to the derivation of a predicted consensus structural model for these elements. This model consists of a stem-loop or hairpin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10334333", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 124, "text": "ECIS elements form stem-loop structures in the 3' untranslated regions (UTR) of eukaryotic mRNAs that encode selenoproteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9256076", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 322, "text": "We report a detailed experimental study of the secondary structures of the SECIS elements ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8634917", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 576, "text": "It is characterized by a stem-loop structure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8634917", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 421, "text": " in eukaryotic selenoprotein mRNAs, this stem-loop structure, the selenocysteine insertion sequence (SECIS) element, resides in the 3'-untranslated region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8602359", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 119, "text": "ECIS elements are stem-loop structures located in the 3' untranslated regions (UTRs) of eukaryotic selenoprotein mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8601283", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 974, "text": "eukaryotic selenocysteine UGA codons requires a stem-loop structure in the 3'UTR of mRNAs, the selenocysteine insertion sequence (SECIS) element", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8955902", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 324, "text": "stem-loops and critical nucleotides similar to those in the SECIS elements ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8344267", "endSection": "abstract" } ] }, { "body": "Is Propofol used for short-term sedation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21257635", "http://www.ncbi.nlm.nih.gov/pubmed/19189080", "http://www.ncbi.nlm.nih.gov/pubmed/1636917", "http://www.ncbi.nlm.nih.gov/pubmed/23155249", "http://www.ncbi.nlm.nih.gov/pubmed/10150552", "http://www.ncbi.nlm.nih.gov/pubmed/10502909", "http://www.ncbi.nlm.nih.gov/pubmed/11575340", "http://www.ncbi.nlm.nih.gov/pubmed/19589243", "http://www.ncbi.nlm.nih.gov/pubmed/12500519", "http://www.ncbi.nlm.nih.gov/pubmed/10853884", "http://www.ncbi.nlm.nih.gov/pubmed/2212256", "http://www.ncbi.nlm.nih.gov/pubmed/22991132", "http://www.ncbi.nlm.nih.gov/pubmed/19448211", "http://www.ncbi.nlm.nih.gov/pubmed/15960715", "http://www.ncbi.nlm.nih.gov/pubmed/12392590", "http://www.ncbi.nlm.nih.gov/pubmed/16741692", "http://www.ncbi.nlm.nih.gov/pubmed/15891317", "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "http://www.ncbi.nlm.nih.gov/pubmed/15774043", "http://www.ncbi.nlm.nih.gov/pubmed/19046459", "http://www.ncbi.nlm.nih.gov/pubmed/15959548", "http://www.ncbi.nlm.nih.gov/pubmed/10757567" ], "ideal_answer": [ "Yes. Propofol is the most frequently used sedating agent for patients with expected duration of ICU admission less than 24 hours. There are numerous studies of its efficacy and comparisons with other sedatives." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4277106", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015742", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016292" ], "type": "yesno", "id": "515d9a42298dcd4e5100000d", "snippets": [ { "offsetInBeginSection": 144, "offsetInEndSection": 263, "text": "The current study explores the incidence and content of dreaming during short-term sedation with sevoflurane or propofo", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577917", "endSection": "sections.0" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1241, "text": "Propofol is the sedative most frequently used for short-term sedation and the weaning phase, whereas benzodiazepines are the preferred substances for medium- and long-term sedation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21257635", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Performance of the A-line Autoregressive Index (AAI) and of the Bispectral Index (BIS) at assessing depth of short-term sedation following cardiac surgery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19589243", "endSection": "title" }, { "offsetInBeginSection": 275, "offsetInEndSection": 352, "text": "All patients received sedation with propofol according to the study protocol.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19589243", "endSection": "sections.0" }, { "offsetInBeginSection": 1881, "offsetInEndSection": 2004, "text": "Short-term sedation with either sevoflurane using ACD or propofol did not negatively affect renal function postoperatively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19448211", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 197, "text": "Assessing feasibility and physiological effects of sedation with sevoflurane, administered with the anesthetic conserving device (AnaConDa), in comparison with propofol and remifentanil.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19189080", "endSection": "sections.0" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1086, "text": "Sevoflurane can be effectively and safely used for short-term sedation of ICU patients with stable hemodynamic conditions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19189080", "endSection": "sections.0" }, { "offsetInBeginSection": 754, "offsetInEndSection": 855, "text": "Propofol was used for most of the patients during short-term sedation (57%) and during weaning (48%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16741692", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Effects of short-term propofol administration on pancreatic enzymes and triglyceride levels in children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960715", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "This prospective, clinical trial evaluated the effects of short-term propofol administration on triglyceride levels and serum pancreatic enzymes in children undergoing sedation for magnetic resonance imaging.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960715", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Dexmedetomidine vs. propofol for short-term sedation of postoperative mechanically ventilated patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15959548", "endSection": "title" }, { "offsetInBeginSection": 76, "offsetInEndSection": 299, "text": "The aim of this study was to compare the efficacy and endocrine response of propofol vs. the new alpha2-agonist dexmedetomidine for sedation in surgical intensive care patients who need postoperative short-term ventilation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15959548", "endSection": "sections.0" }, { "offsetInBeginSection": 504, "offsetInEndSection": 685, "text": "A total of 89 adult, nonemergent, coronary artery bypass graft patients with an expected length of intubation of <24 hrs. METHODS: Patients were randomized to either DEX or propofol", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15891317", "endSection": "sections.0" }, { "offsetInBeginSection": 499, "offsetInEndSection": 661, "text": "The majority of practitioners (82%) use propofol infusion in children in PICU, the main indication being for short-term sedation in children requiring procedures.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12500519", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Pharmacokinetics and effects of propofol 6% for short-term sedation in paediatric patients following cardiac surgery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12392590", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 119, "text": "This paper describes the pharmacokinetics and effects of propofol in short-term sedated paediatric patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12392590", "endSection": "sections.0" }, { "offsetInBeginSection": 194, "offsetInEndSection": 418, "text": "Twenty patients who were expected to require 8 h of post-operative sedation and ventilation were allocated randomly to receive either an infusion of dexmedetomidine 0.2-2.5 microg kg(-1) h(-1) or propofol 1-3 mg kg(-1) h(-1)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11575340", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10853884", "endSection": "title" }, { "offsetInBeginSection": 217, "offsetInEndSection": 723, "text": "The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN were investigated during a short-term infusion and compared with the commercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). METHODS: In a randomised double-blind study, 24 male patients received a 5-h infusion of propofol at the rate of 1 mg/kg/h for sedation in the immediate postoperative period following coronary artery bypass surgery", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10853884", "endSection": "sections.0" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1702, "text": "Propofol infusion and oxycodone-thiopental bolus dosages, titrated to the same sedation end point, resulted in similar time from admission to extubation, although the weaning period was shorter in the propofol group. In terms of breathing pattern, gas exchange, blood gases and haemodynamics, the methods were similar. Propofol, despite its attractive pharmacological profile, may offer no clinical benefit in short-term sedation after a moderate dose fentanyl anaesthesia in cardiac surgery.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10757567", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Postoperative short-term sedation with propofol in cardiac surgery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502909", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "We conducted a randomized double-blind study to assess the safety and effectiveness of short-term sedation with propofol in adult patients immediately after cardiac surgery.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502909", "endSection": "sections.0" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1049, "text": "The use of propofol for short-term sedation in ICUs has allowed the maintenance of sedation to continue until just a few hours before extubation but the benefits of propofol for longer-term indications are more debatable.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10150552", "endSection": "sections.0" }, { "offsetInBeginSection": 363, "offsetInEndSection": 470, "text": "Midazolam and propofol are available as hypnotics for short-term sedation during the post-operative period.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1636917", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The use of midazolam versus propofol for short-term sedation following coronary artery bypass grafting.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2212256", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Midazolam and propofol were compared in an open randomized study for postoperative sedation during 12 h of mechanical ventilation in 40 patients following coronary artery bypass grafting", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2212256", "endSection": "sections.0" }, { "offsetInBeginSection": 183, "offsetInEndSection": 288, "text": "Propofol is a known anesthetic agent, widely used for short-term anesthesia and for longer-term sedation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23155249", "endSection": "sections.0" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1014, "text": "Propofol was the most commonly used agent overall during the observational period (primarily for short-term and intermediate-length sedation); midazolam was the most commonly used for long-term sedation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22991132", "endSection": "sections.0" } ] }, { "body": "Which proteins are the different members of the NF-kappaB family of transcription factors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21122287", "http://www.ncbi.nlm.nih.gov/pubmed/22405852", "http://www.ncbi.nlm.nih.gov/pubmed/9129142", "http://www.ncbi.nlm.nih.gov/pubmed/9950430" ], "ideal_answer": [ "Nuclear factor kappa B (NF\u03baB) is a dimeric transcription factor comprised of five family members RelA (p65), RelB, c-Rel, NF-kB1/p50 and NF-kB2/p52." ], "exact_answer": [ [ "RelA", "p65" ], [ "RelB" ], [ "c-Rel" ], [ "NF-kB1/p50" ], [ "NF-kB2/p52" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4263986", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016328" ], "type": "list", "id": "55192f20622b194345000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The transcription factor NF-kappaB is composed of homodimeric and heterodimeric complexes of Rel/NF-kappaB-family polypeptides, which include Rel-A, c-Rel, Rel-B, NF-kappaB/p50 and NF-kappaB2/p52 .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9950430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Nuclear factor kappa B (NF\u03baB) is a dimeric transcription factor comprised of five family members RelA (p65), RelB, c-Rel, p50 and p52.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22405852", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 491, "text": "In mammals, the genes rela, relb, crel, nfkappa\u03921, and nfkappaB encode the five NF-kB protein family members RelA (p65), RelB, c-Rel, p50, and p52, respectively, which form homo- and heterodimeric DNA-binding complexes capable of regulating target gene transcription of specific biological responses differentially.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21122287", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 873, "text": "These results suggest that the Rel-homology domain can act as an allosteric effector to promote transcription by p50/NFkappaB1 and that the configuration of p50 is important for its activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9129142", "endSection": "abstract" } ] }, { "body": "What are the symptoms of Rotor syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17464171", "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "http://www.ncbi.nlm.nih.gov/pubmed/20955959", "http://www.ncbi.nlm.nih.gov/pubmed/6807787", "http://www.ncbi.nlm.nih.gov/pubmed/11972401", "http://www.ncbi.nlm.nih.gov/pubmed/22982575" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067659", "o": "D006933" } ], "ideal_answer": [ "Rotor syndrome is characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics." ], "exact_answer": [ [ "conjugated hyperbilirubinemia" ], [ "coproporphyrinuria" ], [ "near-absent hepatic uptake of anionic diagnostics" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006932", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006933" ], "type": "list", "id": "571e417bbb137a4b0c00000a", "snippets": [ { "offsetInBeginSection": 210, "offsetInEndSection": 518, "text": "The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that of Rotor syndrome, an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics, has remained enigmatic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "[A case with Rotor syndrome in hyperbilirubinemic family].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17464171", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20955959", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Rotor syndrome is a rare, benign familial disorder characterized by chronic fluctuating, nonhemolytic and predominantly conjugated hyperbilirubinemia with normal hepatic histology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17464171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Jaundice is often the first and sometimes the only symptom of liver disease. Besides in parenchymal liver disease jaundice is also observed in chronic non-haemolytic hyperbilirubinemias (Crigler-Najjar type I and II, Gilbert's syndrome) and in hereditary conjugated hyperbilirubinaemias (Dubin-Johnson- and Rotor-syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6807787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": " Rotor syndrome is a rare, benign familial disorder characterized by chronic fluctuating, nonhemolytic and predominantly conjugated hyperbilirubinemia with normal hepatic histology. In contrast to Dubin-Johnson syndrome, there is no liver pigmentation in Rotor syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17464171", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 742, "text": "The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that of Rotor syndrome, an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics, has remained enigmatic. Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 742, "text": "The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that of Rotor syndrome, an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics, has remained enigmatic. Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20955959", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20955959", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "[A case with Rotor syndrome in hyperbilirubinemic family].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17464171", "endSection": "title" } ] }, { "body": "Does splicing occur co-transcriptionally?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22326677", "http://www.ncbi.nlm.nih.gov/pubmed/22022255", "http://www.ncbi.nlm.nih.gov/pubmed/22955974", "http://www.ncbi.nlm.nih.gov/pubmed/19710184", "http://www.ncbi.nlm.nih.gov/pubmed/19656867", "http://www.ncbi.nlm.nih.gov/pubmed/16440002", "http://www.ncbi.nlm.nih.gov/pubmed/22056773", "http://www.ncbi.nlm.nih.gov/pubmed/19185575", "http://www.ncbi.nlm.nih.gov/pubmed/23638305", "http://www.ncbi.nlm.nih.gov/pubmed/21264352", "http://www.ncbi.nlm.nih.gov/pubmed/20631007", "http://www.ncbi.nlm.nih.gov/pubmed/11602343" ], "ideal_answer": [ "The consensus view, based on four organisms, is that the majority of splicing events take place co-transcriptionally in most cells and tissues. RNA processing events that take place on the transcribed pre-mRNA include capping, splicing, editing, 3' processing, and polyadenylation. Most of these processes occur co-transcriptionally while the RNA polymerase II (Pol II) enzyme is engaged in transcriptional elongation." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045292" ], "type": "yesno", "id": "533c3871c45e133714000007", "snippets": [ { "offsetInBeginSection": 78, "offsetInEndSection": 350, "text": "Researchers working in multiple model organisms - notably yeast, insects and mammalian cells - have shown that pre-mRNA can be spliced during the process of transcription (i.e. co-transcriptionally), as well as after transcription termination (i.e. post-transcriptionally)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23638305", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 895, "text": "The consensus view, based on four organisms, is that the majority of splicing events take place co-transcriptionally in most cells and tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23638305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955974", "endSection": "title" }, { "offsetInBeginSection": 234, "offsetInEndSection": 319, "text": "We show that in the human genome, splicing occurs predominantly during transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955974", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1228, "text": "Consistent with co-transcriptional spliceosome assembly and splicing, we have found significant enrichment of spliceosomal snRNAs in chromatin-associated RNA compared with other cellular RNA fractions and other nonspliceosomal snRNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955974", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 449, "text": "The majority of introns in higher eukaryotes are excised prior to transcript release in a manner that is dependent on transcription through pol II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22326677", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 681, "text": "s a result of co-transcriptional splicing, variations in pol II elongation influence alternative splicing patterns, wherein a slower elongation rate is associated with increased inclusion of alternative exons within mature mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22326677", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 661, "text": "We show that the pattern of intronic sequence read coverage is explained by nascent transcription in combination with co-transcriptional splicing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056773", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 797, "text": "Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22022255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "RNA processing events that take place on the transcribed pre-mRNA include capping, splicing, editing, 3' processing, and polyadenylation. Most of these processes occur co-transcriptionally while the RNA polymerase II (Pol II) enzyme is engaged in transcriptional elongation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21264352", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 266, "text": "Abundant evidence indicates that splicing to excise introns occurs co-transcriptionally, prior to release of the nascent transcript from RNAP II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20631007", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1087, "text": "Together, our work establishes a system for co-transcriptional splicing in vitro, in which the spliceosome containing the 5' and 3' exons are tethered to RNAP II for splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20631007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Co-transcriptional splicing of constitutive and alternative exons", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656867", "endSection": "title" }, { "offsetInBeginSection": 184, "offsetInEndSection": 351, "text": "Current evidence supports co-transcriptional spliceosomal assembly, but there is little quantitative information on how much splicing is completed during RNA synthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656867", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1352, "text": "Thus, we demonstrate that the decision to include or skip an alternative exon is made during transcription and not post-transcriptionally", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656867", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 284, "text": "Here, we demonstrated that the co-transcriptional splicing of the intron in vitro was blocked by antisense oligonucleotides (AONs) targeting the P3-P7 core of the intron", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19185575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "RNA editing and alternative splicing: the importance of co-transcriptional coordination", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16440002", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Co-transcriptional splicing of pre-messenger RNAs: considerations for the mechanism of alternative splicing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11602343", "endSection": "title" }, { "offsetInBeginSection": 226, "offsetInEndSection": 321, "text": "The realization that splicing occurs co-transcriptionally requires two important considerations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11602343", "endSection": "abstract" } ] }, { "body": "List the existing methods for genetic manipulation of cells.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24296066", "http://www.ncbi.nlm.nih.gov/pubmed/12719540", "http://www.ncbi.nlm.nih.gov/pubmed/19678910", "http://www.ncbi.nlm.nih.gov/pubmed/24269346", "http://www.ncbi.nlm.nih.gov/pubmed/24060313", "http://www.ncbi.nlm.nih.gov/pubmed/22675075", "http://www.ncbi.nlm.nih.gov/pubmed/24158830", "http://www.ncbi.nlm.nih.gov/pubmed/24048932", "http://www.ncbi.nlm.nih.gov/pubmed/21249368", "http://www.ncbi.nlm.nih.gov/pubmed/19594452", "http://www.ncbi.nlm.nih.gov/pubmed/16451554", "http://www.ncbi.nlm.nih.gov/pubmed/18556259", "http://www.ncbi.nlm.nih.gov/pubmed/24050263", "http://www.ncbi.nlm.nih.gov/pubmed/24055287", "http://www.ncbi.nlm.nih.gov/pubmed/18988631", "http://www.ncbi.nlm.nih.gov/pubmed/24222505", "http://www.ncbi.nlm.nih.gov/pubmed/24296044" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0086451", "o": "U002966" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0025991", "o": "http://linkedlifedata.com/resource/umls/label/A0086451" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0025991", "o": "http://linkedlifedata.com/resource/umls/label/A0086451" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0086452", "o": "Microinjections" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0483915", "o": "microinjection" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0025991", "o": "http://linkedlifedata.com/resource/umls/label/A0086450" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0086450", "o": "Microinjection" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0025991", "o": "http://linkedlifedata.com/resource/umls/label/A0483915" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0025991", "o": "http://linkedlifedata.com/resource/umls/label/A0086452" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C0040669", "o": "http://linkedlifedata.com/resource/umls/id/C0178659" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0319027", "o": "genetic manipulation" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0040669", "o": "http://linkedlifedata.com/resource/umls/label/A0127589" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0040669", "o": "http://linkedlifedata.com/resource/umls/label/A0490756" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0040669", "o": "http://linkedlifedata.com/resource/umls/label/A0127588" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0127588", "o": "Transfection" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0040669", "o": "http://linkedlifedata.com/resource/umls/label/A0127590" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0127590", "o": "Transfections" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0040669", "o": "http://linkedlifedata.com/resource/umls/label/A0127590" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0490756", "o": "transfection" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0040669", "o": "http://linkedlifedata.com/resource/umls/label/A7574200" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C0872089", "o": "http://linkedlifedata.com/resource/umls/id/C0040669" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0872089", "o": "http://linkedlifedata.com/resource/umls/label/A1883737" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1883737", "o": "transfection/expression vector" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7574200", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0490756", "o": "CRISP Thesaurus" } ], "ideal_answer": [ "Genetic engineering, also called genetic modification, is the direct manipulation of an organism's genome using biotechnology. New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest using molecular cloning methods to generate a DNA sequence, or by synthesizing the DNA, and then inserting this construct into the host organism. Genes may be removed, or \"knocked out\", using a nuclease. Gene targeting is a different technique that uses homologous recombination to change an endogenous gene, and can be used to delete a gene, remove exons, add a gene, or introduce point mutations. Based on results there are developed many methods for genetic manipulation of cells such as Microinjection, electroporation, liposomes and via viral vectors.", "The existing methods for genetic manipulation of cells include Agrobacterium-mediated or direct delivery methods, as well as methods using plant artificial chromosomes, site-directed plasmid mutagenesis, combined use of Red/ET recombination and unique restriction site elimination, Bacterial artificial chromosomes (BACs), direct in vitro transposition of viral genomes with a BAC cassette, and subsequent recovery in Escherichia coli, as well as transformation-competent artificial chromosome (TAC)-based acceptor vector, by exploiting the CreloxP recombination system and homing endonucleases." ], "exact_answer": [ [ "Agrobacterium-mediated delivery" ], [ "direct delivery methods" ], [ "methods using plant artificial chromosomes" ], [ "site-directed plasmid mutagenesis" ], [ "combined use of Red/ET recombination and unique restriction site elimination" ], [ "Bacterial artificial chromosomes (BACs)" ], [ "direct in vitro transposition of viral genomes with a BAC cassette, and subsequent recovery in Escherichia coli" ], [ "transformation-competent artificial chromosome (TAC)-based acceptor vector, by exploiting the CreloxP recombination system and homing endonucleases" ], [ "Microinjection" ], [ "electroporation" ], [ "viral vectors" ], [ "liposomes" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053672", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009292", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008967", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008845", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039361", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018274", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055614", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015316", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005826", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014158", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005821", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D036281", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005823", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005822", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006579", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820" ], "type": "list", "id": "52fa73e82059c6d71c000059", "snippets": [ { "offsetInBeginSection": 285, "offsetInEndSection": 749, "text": "For efficient genetic transformation, Agrobacterium-mediated as well as direct delivery methods have been used successfully. However, these methods suffer from many disadvantages especially in terms of transfer of large genes, gene complexes and gene silencing. To overcome these problems, recently, some efforts have been made to develop genetic transformation systems based on engineered plant chromosomes called minichromosomes or plant artificial chromosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "Existing methods for site-directed plasmid mutagenesis are restrained by the small spectrum of modifications that can be introduced by mutagenic primers and the amplicon size limitations of in vitro DNA synthesis. As demonstrated here, the combined use of Red/ET recombination and unique restriction site elimination enables extensive manipulation regardless of plasmid size and DNA sequence elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19594452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Bacterial artificial chromosomes (BACs) derived from genomes of large DNA viruses are powerful tools for functional delineation of viral genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18988631", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 790, "text": "Here, we describe a novel method for cloning the genomes of large DNA viruses as BACs, which entails direct in vitro transposition of viral genomes with a BAC cassette, and subsequent recovery in Escherichia coli. Determination of insertion sites and adjacent viral sequences identify the BAC clones for genetic manipulation and functional characterization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18988631", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 678, "text": "Here, we describe a vector system for efficient multigene assembly and transformation. The system consists of a transformation-competent artificial chromosome (TAC)-based acceptor vector together with two donor vectors. By exploiting the CreloxP recombination system and homing endonucleases, multiple rounds of gene assembly cycling were carried out with alternate use of the donor vectors, and multiple genes were sequentially delivered into the TAC vector.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12719540", "endSection": "abstract" } ] }, { "body": "Are there clinical trials on stem cells in multiple sclerosis", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18562508", "http://www.ncbi.nlm.nih.gov/pubmed/21366911", "http://www.ncbi.nlm.nih.gov/pubmed/23197667", "http://www.ncbi.nlm.nih.gov/pubmed/23124791", "http://www.ncbi.nlm.nih.gov/pubmed/12376881", "http://www.ncbi.nlm.nih.gov/pubmed/15764028", "http://www.ncbi.nlm.nih.gov/pubmed/23331685", "http://www.ncbi.nlm.nih.gov/pubmed/20413685", "http://www.ncbi.nlm.nih.gov/pubmed/22359549", "http://www.ncbi.nlm.nih.gov/pubmed/21440544", "http://www.ncbi.nlm.nih.gov/pubmed/22561409" ], "ideal_answer": [ "Yes. Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for multiple sclerosis. Several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013234", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049109", "http://www.disease-ontology.org/api/metadata/DOID:2377", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103" ], "type": "yesno", "id": "515df5b2298dcd4e5100002c", "snippets": [ { "offsetInBeginSection": 1033, "offsetInEndSection": 1180, "text": "Cells are generally given intravenously. Multiple sclerosis, rheumatoid arthritis and lupus have been successfully treated in human clinical trials", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23331685", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for Crohn's disease, multiple sclerosis, graft-versus-host disease, type 1 diabetes, bone fractures, cartilage damage, and cardiac diseases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23197667", "endSection": "sections.0" }, { "offsetInBeginSection": 585, "offsetInEndSection": 1028, "text": "Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124791", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561409", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Autologous bone marrow stromal cells (BMSCs) offer significant practical advantages for potential clinical applications in multiple sclerosis (MS). Based on recent experimental data, a number of clinical trials have been designed for the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21440544", "endSection": "sections.0" }, { "offsetInBeginSection": 341, "offsetInEndSection": 520, "text": "Fingolimod is a S1P receptor modulator in MS clinical trials due to systemic anti-inflammatory properties, yet may impact cells within the CNS by crossing the blood-brain barrier.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20413685", "endSection": "sections.0" }, { "offsetInBeginSection": 123, "offsetInEndSection": 477, "text": "Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on \"Stem Cells & MS: Prospects and Strategies\"", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18562508", "endSection": "sections.0" }, { "offsetInBeginSection": 161, "offsetInEndSection": 287, "text": "Here we discuss key observations and questions emerging from clinical trials of hematopoietic stem cell transplantation for MS", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15764028", "endSection": "sections.0" }, { "offsetInBeginSection": 457, "offsetInEndSection": 731, "text": "Another possibility to achieve remyelination is the transplantation of myelinating cells into the central nervous system. Proof of principle and demonstration of the functionality were shown in numerous experiments, and a first clinical trial in patients with MS has started", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12376881", "endSection": "sections.0" }, { "offsetInBeginSection": 850, "offsetInEndSection": 997, "text": "This first trial will show if cell transplantation is a feasible concept in MS and whether the transplanted cells will survive and form new myelin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12376881", "endSection": "sections.0" } ] }, { "body": "Which SWI/SNF protein complex subunit has been demonstrated to interact with the FANCA gene product?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11726552" ], "ideal_answer": [ "The Fanconi anemia protein FANCA has been shown to interact with the brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity.", "FANCA was demonstrated to associate with the endogenous SWI/SNF complexFANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair" ], "exact_answer": [ "BRG1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052217" ], "type": "factoid", "id": "54edf81f94afd61504000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "title" }, { "offsetInBeginSection": 111, "offsetInEndSection": 325, "text": "We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 398, "text": "FANCA was demonstrated to associate with the endogenous SWI/SNF complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1131, "text": "FANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "title" }, { "offsetInBeginSection": 111, "offsetInEndSection": 208, "text": "We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 887, "text": "Finally, we demonstrated co-localization in the nucleus between transfected FANCA and BRG1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 207, "text": "We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 886, "text": "Finally, we demonstrated co-localization in the nucleus between transfected FANCA and BRG1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726552", "endSection": "abstract" } ] }, { "body": "Are piRNAs involved in gene silencing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23465540", "http://www.ncbi.nlm.nih.gov/pubmed/20559422", "http://www.ncbi.nlm.nih.gov/pubmed/20080197", "http://www.ncbi.nlm.nih.gov/pubmed/25842866", "http://www.ncbi.nlm.nih.gov/pubmed/20439430", "http://www.ncbi.nlm.nih.gov/pubmed/26302790", "http://www.ncbi.nlm.nih.gov/pubmed/23392610", "http://www.ncbi.nlm.nih.gov/pubmed/23124062", "http://www.ncbi.nlm.nih.gov/pubmed/17872506", "http://www.ncbi.nlm.nih.gov/pubmed/25336588", "http://www.ncbi.nlm.nih.gov/pubmed/23625890", "http://www.ncbi.nlm.nih.gov/pubmed/25313140", "http://www.ncbi.nlm.nih.gov/pubmed/24288375", "http://www.ncbi.nlm.nih.gov/pubmed/26472911", "http://www.ncbi.nlm.nih.gov/pubmed/21764773", "http://www.ncbi.nlm.nih.gov/pubmed/21775629", "http://www.ncbi.nlm.nih.gov/pubmed/18809914", "http://www.ncbi.nlm.nih.gov/pubmed/24939875", "http://www.ncbi.nlm.nih.gov/pubmed/26279487", "http://www.ncbi.nlm.nih.gov/pubmed/23132912", "http://www.ncbi.nlm.nih.gov/pubmed/24178563" ], "ideal_answer": [ "Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire. Transcriptional silencing implies a piRNA-mediated formation of repressive chromatin which diminishes the transcriptional capacity of the target locus." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016458", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020868" ], "type": "yesno", "id": "56c6f6005795f9a73e000009", "snippets": [ { "offsetInBeginSection": 135, "offsetInEndSection": 304, "text": "In Drosophila ovaries, the nuclear Piwi protein is required for transcriptional silencing of transposons, though the precise mechanisms by which this occurs are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26472911", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 643, "text": "Here we show that the CG9754 protein is a component of Piwi complexes that functions downstream of Piwi and its binding partner, Asterix, in transcriptional silencing. Enforced tethering of CG9754 to nascent messenger RNA transcripts causes cotranscriptional silencing of the source locus and the deposition of repressive chromatin marks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26472911", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 878, "text": "We have named CG9754 \"Panoramix,\" and we propose that this protein could act as an adaptor, scaffolding interactions between the piRNA pathway and the general silencing machinery that it recruits to enforce transcriptional repression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26472911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26302790", "endSection": "title" }, { "offsetInBeginSection": 161, "offsetInEndSection": 298, "text": "Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26279487", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 460, "text": "To assess the dysregulation of gene silencing caused by lack of piRNAs, we restored RNA silencing in RNAi-defective animals in the presence or absence of piRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26279487", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1010, "text": "Thus, by reanimating RNAi, we uncovered a role for piRNAs in protecting essential genes from RNA silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26279487", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 464, "text": "In different organisms, small RNAs were shown to be implicated in the posttranscriptional degradation of mRNA and/or transcriptional repression of the homologous locus. In Drosophila, the mechanism of piRNA-mediated silencing is still far from being understood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24178563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Analyses of piRNA-mediated transcriptional transposon silencing in Drosophila", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24178563", "endSection": "title" }, { "offsetInBeginSection": 466, "offsetInEndSection": 617, "text": "Transcriptional silencing implies a piRNA-mediated formation of repressive chromatin which diminishes the transcriptional capacity of the target locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24178563", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 572, "text": "In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24939875", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 430, "text": "Using a candidate gene KD-approach, we identified differences in the spatio-temporal requirements of the piRNA pathway components for piRNA-mediated silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24288375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Spatio-temporal requirements for transposable element piRNA-mediated silencing during Drosophila oogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24288375", "endSection": "title" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1286, "text": "In contrast, piRNA-mediated silencing is strong in germline stem cells in which TE mobilization is tightly repressed ensuring the continued production of viable germline cysts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24288375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23392610", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "In germ cells, early embryos, and stem cells of animals, PIWI-interacting RNAs (piRNAs) have an important role in silencing retrotransposons, which are vicious genomic parasites, through transcriptional and post-transcriptional mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23132912", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1148, "text": "Our results show that the piRNA pathway can be used as a tool for sequence-specific gene silencing in germ cells and support the idea that the piRNA generating regions serve as traps for retrotransposons, enabling the host cell to generate piRNAs against active retrotransposons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23132912", "endSection": "abstract" }, { "offsetInBeginSection": 1627, "offsetInEndSection": 1820, "text": " Our observations confirm the pivotal role of piRNA-mediated silencing in defending the genome against selfish transposition, yet also suggest limits to the optimization of host genome defense.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Analysis of piRNA-mediated silencing of active TEs in Drosophila melanogaster suggests limits on the evolution of host genome defense", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625890", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of transposable element (TE) infection by imposing small-RNA-mediated silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "A novel organelle, the piNG-body, in the nuage of Drosophila male germ cells is associated with piRNA-mediated gene silencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21775629", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Proteins of the PIWI subfamily Aub and AGO3 associated with the germline-specific perinuclear granules (nuage) are involved in the silencing of retrotransposons and other selfish repetitive elements in the Drosophila genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21775629", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 256, "text": "Telomeric retroelements HeT-A, TART and TAHRE, which are involved in telomere maintenance in Drosophila, are also the targets of piRNA-mediated silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Mechanism of the piRNA-mediated silencing of Drosophila telomeric retrotransposons.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764773", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17872506", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The epigenetic trans-silencing effect in Drosophila involves maternally-transmitted small RNAs whose production depends on the piRNA pathway and HP1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20559422", "endSection": "title" }, { "offsetInBeginSection": 652, "offsetInEndSection": 798, "text": "Here, we show that mutations in squash and zucchini, which are involved in the piwi-interacting RNA (piRNA) silencing pathway, strongly affect TSE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20559422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "MVH in piRNA processing and gene silencing of retrotransposons", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439430", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "piRNA-mediated silencing in Drosophila germlines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080197", "endSection": "title" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1110, "text": "These have shed light not only on the molecular mechanisms of gene silencing mediated by piRNAs and PIWI proteins, but also on their intriguing relationship with cellular genes that have been shown to be important for gametogenesis and fertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080197", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 794, "text": "The most abundant piRNAs were those corresponding to antisense transcripts of Suppressor of Stellate [Su(Ste)] genes known to be involved in Stellate gene silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17872506", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 478, "text": "To determine the capacity of piRNA-mediated silencing, we introduced reporter genes into Drosophila OSS cells, which express microRNAs (miRNAs) and piRNAs, and compared the Piwi pathway to the Argonaute pathway in gene regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25336588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "PIWI-interacting small non-coding RNAs (piRNAs) are genetic and epigenetic regulatory factors in germline cells, where they maintain genome stability, are involved in RNA silencing and regulate gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25313140", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 318, "text": "The piNG-body contains ribonucleoprotein complexes involved in piRNA-silencing of genome repeats including transposons in premeiotic spermatocytes with aid of short piRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25842866", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1147, "text": "Our results show that the piRNA pathway can be used as a tool for sequence-specific gene silencing in germ cells and support the idea that the piRNA generating regions serve as traps for retrotransposons, enabling the host cell to generate piRNAs against active retrotransposons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23132912", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 375, "text": "Recent studies have revealed not only the biogenesis of piRNAs and their roles in transposon silencing, but also the function of the Piwi-piRNA pathway in epigenetic and post-transcriptional regulation of gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23465540", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 541, "text": "A growing number of studies on piRNAs have investigated piRNA-mediated gene silencing, including piRNA biogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124062", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1109, "text": "These have shed light not only on the molecular mechanisms of gene silencing mediated by piRNAs and PIWI proteins, but also on their intriguing relationship with cellular genes that have been shown to be important for gametogenesis and fertility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080197", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 258, "text": "Telomeric retroelements HeT-A, TART and TAHRE, which are involved in telomere maintenance in Drosophila, are also the targets of piRNA-mediated silencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "MVH in piRNA processing and gene silencing of retrotransposons.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439430", "endSection": "title" }, { "offsetInBeginSection": 249, "offsetInEndSection": 480, "text": "To determine the capacity of piRNA-mediated silencing, we introduced reporter genes into Drosophila OSS cells, which express microRNAs (miRNAs) and piRNAs, and compared the Piwi pathway to the Argonaute pathway in gene regulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25336588", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1356, "text": "Therefore piRNA-mediated transcriptional mode of silencing is involved in the control of retrotransposon expression in the Drosophila germline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Panoramix enforces piRNA-dependent cotranscriptional silencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26472911", "endSection": "title" }, { "offsetInBeginSection": 631, "offsetInEndSection": 796, "text": "The most abundant piRNAs were those corresponding to antisense transcripts of Suppressor of Stellate [Su(Ste)] genes known to be involved in Stellate gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17872506", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1602, "text": "Our results indicate that piRNAs are involved in a posttranscriptional gene-silencing mechanism resulting in RNA nuclear accumulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18809914", "endSection": "abstract" } ] }, { "body": "List representatives of the major fungal hypoxanthine-adenine-guanine transporter families.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14597637", "http://www.ncbi.nlm.nih.gov/pubmed/19121308", "http://www.ncbi.nlm.nih.gov/pubmed/24818808", "http://www.ncbi.nlm.nih.gov/pubmed/16923723", "http://www.ncbi.nlm.nih.gov/pubmed/7721763" ], "ideal_answer": [ "AzgA and Fcy21p are prototypes of the two major fungal hypoxanthine-adenine-guanine transporter families." ], "exact_answer": [ [ "AzgA" ], [ "Fcy21p" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035345" ], "type": "list", "id": "554397f6ed966d112c00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Comparative kinetic analysis of AzgA and Fcy21p, prototypes of the two major fungal hypoxanthine-adenine-guanine transporter families", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16923723", "endSection": "title" }, { "offsetInBeginSection": 190, "offsetInEndSection": 421, "text": "We carried out a comparative kinetic analysis of two prototypes of these transporter families. The first was Fcy21p, a herein characterized protein of Candida albicans, and the second was AzgA, a transporter of Aspergillus nidulans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16923723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The azgA gene of Aspergillus nidulans encodes a hypoxanthine-adenine-guanine transporter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14597637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "In Aspergillus nidulans, loss-of-function mutations in the uapA and azgA genes, encoding the major uric acid-xanthine and hypoxanthine-adenine-guanine permeases, respectively, result in impaired utilization of these purines as sole nitrogen sources", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7721763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Comparative kinetic analysis of AzgA and Fcy21p, prototypes of the two major fungal hypoxanthine-adenine-guanine transporter families.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16923723", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The azgA gene of Aspergillus nidulans encodes a hypoxanthine-adenine-guanine transporter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14597637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "In Aspergillus nidulans, loss-of-function mutations in the uapA and azgA genes, encoding the major uric acid-xanthine and hypoxanthine-adenine-guanine permeases, respectively, result in impaired utilization of these purines as sole nitrogen sources.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7721763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Modelling, substrate docking and mutational analysis identify residues essential for function and specificity of the major fungal purine transporter AzgA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24818808", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 302, "text": "In Arabidopsis two proteins, AtAzg1 and AtAzg2, show substantial amino acid sequence similarity to the adenine-guanine-hypoxanthine transporter AzgA of Aspergillus nidulans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19121308", "endSection": "abstract" } ] }, { "body": "Which proteins have been identified as RET ligands?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11973622", "http://www.ncbi.nlm.nih.gov/pubmed/9764818", "http://www.ncbi.nlm.nih.gov/pubmed/9284737", "http://www.ncbi.nlm.nih.gov/pubmed/11324313", "http://www.ncbi.nlm.nih.gov/pubmed/9192898", "http://www.ncbi.nlm.nih.gov/pubmed/9885824", "http://www.ncbi.nlm.nih.gov/pubmed/12668632", "http://www.ncbi.nlm.nih.gov/pubmed/9473110", "http://www.ncbi.nlm.nih.gov/pubmed/16294336", "http://www.ncbi.nlm.nih.gov/pubmed/11106284", "http://www.ncbi.nlm.nih.gov/pubmed/17638907", "http://www.ncbi.nlm.nih.gov/pubmed/10321971", "http://www.ncbi.nlm.nih.gov/pubmed/9700200", "http://www.ncbi.nlm.nih.gov/pubmed/11409869", "http://www.ncbi.nlm.nih.gov/pubmed/10652334", "http://www.ncbi.nlm.nih.gov/pubmed/10822229", "http://www.ncbi.nlm.nih.gov/pubmed/22753894", "http://www.ncbi.nlm.nih.gov/pubmed/15013219", "http://www.ncbi.nlm.nih.gov/pubmed/10790203", "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "http://www.ncbi.nlm.nih.gov/pubmed/10027003", "http://www.ncbi.nlm.nih.gov/pubmed/18970938" ], "ideal_answer": [ "RET is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin, artemin, and persephin.", "The RET proto-oncogene encodes a receptor tyrosine kinase, which is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN)." ], "exact_answer": [ [ "GDNF", "glial cell-line-derived neurotrophic factor" ], [ "ARTN", "artemin" ], [ "NTN", "neurturin" ], [ "PSPN", "persephin" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008024", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051096" ], "type": "list", "id": "551910d3622b194345000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Polymorphisms in the genes encoding the 4 RET ligands, GDNF, NTN, ARTN, PSPN, and susceptibility to Hirschsprung disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18970938", "endSection": "title" }, { "offsetInBeginSection": 507, "offsetInEndSection": 649, "text": "Given the pivotal role of RET in HSCR, the genes encoding their ligands (GDNF, NRTN, ARTN, and PSPN) are also good candidates for the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18970938", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1308, "text": "Indeed, the RET ligands persephin and GDNF robustly stimulated calcitonin mRNA, which was blocked by pretreatment with NVP-AST487", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17638907", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 301, "text": "The ligands bind RET through GDNF family receptor alpha, termed GFRalpha1-4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16294336", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 224, "text": "RET is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin, artemin, and persephin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16294336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "GDNF availability determines enteric neuron number by controlling precursor proliferation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12668632", "endSection": "title" }, { "offsetInBeginSection": 217, "offsetInEndSection": 365, "text": "Five germline mutations in the glial cell-line-derived neurotrophic factor (GDNF) gene, one of the RET ligands, have been detected in HSCR patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11973622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The glial-cell-line-derived neurotrophic factor (GDNF) family receptors alpha (GFRalpha) are cell surface bound glycoproteins that mediate interactions of the GDNF ligand family with the RET receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11409869", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1035, "text": "In particular, the recent identification of neurotrophic factors acting as RET ligands (GDNF and Neurturin) provide additional candidate genes for HSCR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11324313", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 663, "text": "Mutations in genes that encode RET ligands (GDNF and NTN); components of another signaling pathway (EDNRB, EDN3, ECE-1); and the transcription factor, SOX10, have been identified in HSCR patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11106284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Expression of RET and its ligand complexes, GDNF/GFRalpha-1 and NTN/GFRalpha-2, in medullary thyroid carcinomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10822229", "endSection": "title" }, { "offsetInBeginSection": 214, "offsetInEndSection": 418, "text": "Mutations in the GDNF gene, and encoding one of the RET ligands, either alone or in combination with RET mutations, can also cause HSCR, as can mutations in four other genes (EDN3, EDNRB, ECE1, and SOX10)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790203", "endSection": "abstract" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1036, "text": "In particular, the recent identification of neurotrophic factors acting as RET ligands (GDNF and Neurturin) provide additional candidate genes for HSCR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9885824", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 260, "text": "Ret ligands have been recently identified as the neuron survival factor GDNF (Glial-Derived Neurotrophic Factor) and Neurturin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9764818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9700200", "endSection": "title" }, { "offsetInBeginSection": 300, "offsetInEndSection": 555, "text": "Considering that RET and glial cell line-derived neurotrophic factor (GDNF) mutations have been reported in the disease, we regarded the other RET ligand, neurturin (NTN), as an attractive candidate gene, especially as it shares large homologies with GDNF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9700200", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 648, "text": "Given the pivotal role of RET in HSCR, the genes encoding their ligands (GDNF, NRTN, ARTN, and PSPN) are also good candidates for the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18970938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The c-ret protooncogene, RET, encodes a receptor tyrosine kinase. RET is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin, artemin, and persephin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16294336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Glial cell line-derived neurotrophic factor (GDNF), a ligand of RET tyrosine kinase, and its family ligands promote the survival and differentiation of a variety of neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15013219", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 615, "text": "We demonstrate here that, after injury, the absence of c-Jun specifically in SCs caused impaired axonal regeneration and severely increased neuronal cell death. c-Jun deficiency resulted in decreased expression of several neurotrophic factors, and GDNF and Artemin, both of which encode ligands for the Ret receptor tyrosine kinase, were identified as novel direct c-Jun target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753894", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 611, "text": "GDNF, now known to be the first identified member of a family of factors, signals through the previously known receptor tyrosine kinase, Ret. Unlike most ligands for receptor tyrosine kinases, GDNF does not bind and activate Ret directly, but requires the presence of GPI-linked coreceptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10321971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND/PURPOSE: In 1996, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET transmembrane receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9473110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The ret proto-oncogene encodes a receptor tyrosine kinase whose ligands belong to the glial cell line-derived neurotrophic factor (GDNF) protein family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10027003", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 225, "text": "RET is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin, artemin, and persephin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16294336", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 259, "text": "Ret ligands have been recently identified as the neuron survival factor GDNF (Glial-Derived Neurotrophic Factor) and Neurturin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9764818", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 968, "text": "Glial cell line-derived neurotrophic factor (GDNF) and its receptor molecule GDNFR-alpha, have recently been identified as members of the RET ligand binding complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9284737", "endSection": "abstract" }, { "offsetInBeginSection": 1305, "offsetInEndSection": 1412, "text": "Recently, the Glial cell line-derived neurotrophic factor (GDNF) has been identified to be a ligand for RET", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 1027, "text": "Replacing short segments of GDNF with the homologous segments from persephin (PSPN) (which cannot bind or activate GFRalpha1.RET or GFRalpha2.RET) identified sites along the second finger of GDNF critical for activating the GFRalpha1.RET and GFRalpha2.RET receptor complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10652334", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 407, "text": "GDNF mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-alpha) and the transmembrane protein tyrosine kinase Ret", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9192898", "endSection": "abstract" } ] }, { "body": "Which substances are dangerous to g6PD deficient individuals?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23690191", "http://www.ncbi.nlm.nih.gov/pubmed/22963789", "http://www.ncbi.nlm.nih.gov/pubmed/17355169", "http://www.ncbi.nlm.nih.gov/pubmed/22018328", "http://www.ncbi.nlm.nih.gov/pubmed/23664599", "http://www.ncbi.nlm.nih.gov/pubmed/23874116", "http://www.ncbi.nlm.nih.gov/pubmed/23275730", "http://www.ncbi.nlm.nih.gov/pubmed/23483616", "http://www.ncbi.nlm.nih.gov/pubmed/22171972", "http://www.ncbi.nlm.nih.gov/pubmed/23282778", "http://www.ncbi.nlm.nih.gov/pubmed/23065279" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12020866", "o": "134700" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12020866", "o": "FAVISM, SUSCEPTIBILITY TO" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851319", "o": "http://linkedlifedata.com/resource/umls/label/A12020866" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2385", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/G6PD" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/G6PD", "o": "G6PD" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2385", "o": "http://purl.org/net/tcm/tcm.lifescience.ntu.edu.tw/id/disease/Favism" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/398", "o": "http://data.linkedct.org/resource/condition/4823" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/G6PD", "o": "http://purl.org/net/tcm/tcm.lifescience.ntu.edu.tw/id/gene/G6PD" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/condition/4823", "o": "Condition #4823 (Favism)" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_name", "s": "http://data.linkedct.org/resource/condition/4823", "o": "Favism" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2385", "o": "http://data.linkedct.org/resource/condition/4823" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/398", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/G6PD" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12020866", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "UMLS_CUI:C0015702" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "Favism (disorder)" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "favism" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "NCI2009_04D:C34607" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "SNOMEDCT_2010_1_31:267558001" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "SNOMEDCT_2010_1_31:191172001" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "SNOMEDCT_2010_1_31:154801000" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "MSH2010_2010_02_22:D005236" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13628", "o": "SNOMEDCT_2010_1_31:76500009" } ], "ideal_answer": [ "Antimalarial drugs (primaquine, pamaquine, chloriquine), fava beans, sulfonamides, some antibiotics( nalidixic acid, nitrofurantoin, isoniazid, dapsone, and furazolidone) and henna" ], "exact_answer": [ [ "primaquine" ], [ "pamaquine" ], [ "chloroquine" ], [ "fava beans" ], [ "sulfonamides" ], [ "antibiotics" ], [ "henna" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005955", "http://www.uniprot.org/uniprot/FGD_BEUC1", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007206", "http://www.uniprot.org/uniprot/G6PD_BACSU", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004345" ], "type": "list", "id": "5314b20bdae131f847000005", "snippets": [ { "offsetInBeginSection": 940, "offsetInEndSection": 1000, "text": "The principal clinical manifestation encountered was favism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23065279", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 349, "text": "G6PD deficiency is the most common enzymopathy of red blood cells. The clinical symptoms of favism are jaundice, hematuria and haemolytic anaemia that seem to affect liver and kidney in long term. Thus we evaluate kidney and liver function of favism patients in an endemic area of the disease with a high rate of fava beans cultivation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23483616", "endSection": "abstract" } ] }, { "body": "Which mutations of SCN5A gene are implicated in Brugada syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20129283", "http://www.ncbi.nlm.nih.gov/pubmed/22984773", "http://www.ncbi.nlm.nih.gov/pubmed/21397042", "http://www.ncbi.nlm.nih.gov/pubmed/18341814", "http://www.ncbi.nlm.nih.gov/pubmed/15863661", "http://www.ncbi.nlm.nih.gov/pubmed/22529811", "http://www.ncbi.nlm.nih.gov/pubmed/10727653", "http://www.ncbi.nlm.nih.gov/pubmed/19377070", "http://www.ncbi.nlm.nih.gov/pubmed/19648062", "http://www.ncbi.nlm.nih.gov/pubmed/17442746", "http://www.ncbi.nlm.nih.gov/pubmed/11420310", "http://www.ncbi.nlm.nih.gov/pubmed/24317018", "http://www.ncbi.nlm.nih.gov/pubmed/22277643", "http://www.ncbi.nlm.nih.gov/pubmed/17675083", "http://www.ncbi.nlm.nih.gov/pubmed/22490985", "http://www.ncbi.nlm.nih.gov/pubmed/20609320", "http://www.ncbi.nlm.nih.gov/pubmed/15851320", "http://www.ncbi.nlm.nih.gov/pubmed/17081365", "http://www.ncbi.nlm.nih.gov/pubmed/23538271", "http://www.ncbi.nlm.nih.gov/pubmed/12693506", "http://www.ncbi.nlm.nih.gov/pubmed/19345130", "http://www.ncbi.nlm.nih.gov/pubmed/11748104", "http://www.ncbi.nlm.nih.gov/pubmed/17399644", "http://www.ncbi.nlm.nih.gov/pubmed/15877619", "http://www.ncbi.nlm.nih.gov/pubmed/11960580", "http://www.ncbi.nlm.nih.gov/pubmed/14625171", "http://www.ncbi.nlm.nih.gov/pubmed/23085483", "http://www.ncbi.nlm.nih.gov/pubmed/17141278", "http://www.ncbi.nlm.nih.gov/pubmed/12051963", "http://www.ncbi.nlm.nih.gov/pubmed/18599870", "http://www.ncbi.nlm.nih.gov/pubmed/17075016", "http://www.ncbi.nlm.nih.gov/pubmed/19272188", "http://www.ncbi.nlm.nih.gov/pubmed/19406494", "http://www.ncbi.nlm.nih.gov/pubmed/15277732", "http://www.ncbi.nlm.nih.gov/pubmed/11823453", "http://www.ncbi.nlm.nih.gov/pubmed/10690282", "http://www.ncbi.nlm.nih.gov/pubmed/10664447", "http://www.ncbi.nlm.nih.gov/pubmed/15338453", "http://www.ncbi.nlm.nih.gov/pubmed/11786529", "http://www.ncbi.nlm.nih.gov/pubmed/11150514", "http://www.ncbi.nlm.nih.gov/pubmed/16325048", "http://www.ncbi.nlm.nih.gov/pubmed/21321465" ], "ideal_answer": [ "The following mutations of SCN5A gene have been linked to Brugada syndrome:I137M, p.W1095X; c.3284G>A, R27H, E901K, G1743R, V728I, N1443S, E1152X, c.664C>T; p.Arg222X, Ala2>Thr, Ala735, Ala735>Thr, Val1340>Ile, IVS18-1G>A, E1784K (14x), F861WfsX90 (11x), D356N (8x), G1408R (7x), G400A, H558R, W822X, Q55X, V95I, A1649V, delF1617, c.4810+3_4810+6dupGGGT, K1527R, A1569P, R367H, A735V, R1192Q, D1795." ], "exact_answer": [ [ "I137M" ], [ "p.W1095X, c.3284G>A" ], [ "R27H" ], [ "E901K" ], [ "G1743R" ], [ "V728I" ], [ "N1443S" ], [ "E1152X" ], [ "c.664C>T; p.Arg222X" ], [ "Ala2>Thr, Ala735" ], [ "Ala735>Thr" ], [ "Val1340>Ile" ], [ "IVS18-1G>A" ], [ "E1784K (14x)" ], [ "F861WfsX90 (11x)" ], [ "D356N (8x)" ], [ "G1408R (7x)" ], [ "G400A" ], [ "H558R" ], [ "W822X" ], [ "Q55X" ], [ "V95I" ], [ "A1649V" ], [ "delF1617" ], [ "c.4810+3_4810+6dupGGGT" ], [ "K1527R" ], [ "A1569P" ], [ "R367H" ], [ "A735V" ], [ "R1192Q" ], [ "D1795" ], [ "p.I848fs" ], [ "p.R965C" ], [ "p.1876insM" ], [ "R1232W/T1620M" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053840", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062554", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "list", "id": "52fb78d82059c6d71c000068", "snippets": [ { "offsetInBeginSection": 1594, "offsetInEndSection": 1744, "text": "This was the first study to systematically investigate sodium channel variants in Chinese patients with ARVD; a new SCN5A mutation, I137M, was found. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24317018", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 572, "text": "We describe a family showing the association between Brugada syndrome and epilepsy in which a known mutation in the SCN5A gene (p.W1095X, c.3284G>A) was identified. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538271", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 767, "text": "Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22984773", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 509, "text": "Brugada syndrome (BrS) is a life-threatening arrhythmia disorder associated with autosomal-dominant mutations in the SCN5A gene. We aimed to characterize the diagnostic challenges and clinical manifestations of a novel SCN5A mutation associated with BrS. RESULTS: From a novel SCN5A mutation (c.664C>T; p.Arg222X) identified in a proband with the characteristic electrocardiographic pattern and the history of sudden collapse, 122 family members were studied including 40 carriers of the mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22277643", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 542, "text": "We analyzed the sequence of this gene in 25 Spanish patients with Brugada syndrome. In 4 (16%), we found mutations that had not previously been described: three were amino acid changes (i.e. Ala2>Thr, Ala735>Thr and Val1340>Ile) and one was an intron mutation that affected messenger RNA processing (i.e. IVS18-1G>A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20609320", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1286, "text": "The 4 most frequent BrS1-associated mutations were E1784K (14x), F861WfsX90 (11x), D356N (8x), and G1408R (7x).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129283", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 727, "text": "One missense mutation (G400A) in SCN5A was detected in a conserved region among the cohort of 19 patients. A H558R polymorphism was detected on the same allele. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19345130", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 607, "text": "Thus, we studied the functional restoration of nonsense-mutated SCN5A. RESULTS: HEK293 cells were transfected with SCN5A cDNA or its mutant carrying W822X, a nonsense mutation associated with Brugada syndrome and sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19377070", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 817, "text": "Among the cohort of 19 patients, one missense mutation (G400A) in SCN5A was detected in a conserved region. An H558R polymorphism was detected on the same allele.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17675083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Novel SCN5A mutation (Q55X) associated with age-dependent expression of Brugada syndrome presenting as neurally mediated syncope.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17399644", "endSection": "title" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1337, "text": "A novel nonsense SCN5A mutation (Q55X) was identified in the proband, his mother, and his asymptomatic brother.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17399644", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 87, "text": "Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V and delF1617", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17081365", "endSection": "title" }, { "offsetInBeginSection": 419, "offsetInEndSection": 693, "text": "An intronic mutation (c.4810+3_4810+6dupGGGT) in the SCN5A gene, located outside the consensus splice site, was detected in this study in a family with a highly variable clinical phenotype of Brugada syndrome and/or conduction disease and in a patient with Brugada syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15863661", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 608, "text": "We genetically screened 30 asymptomatic probands (29 men and 1 woman; mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of patients with Brugada syndrome were excluded from the study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851320", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1167, "text": "Genetic screening failed to identify SCN5A mutations in most cases but demonstrated a novel double missense mutation (K1527R and A1569P) located on the same allele in another asymptomatic subject (case 2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851320", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 448, "text": "We screened patients with SUNDS for mutations in SCN5A, the gene known to cause Brugada syndrome, as well as genes encoding ion channels associated with the long-QT syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11823453", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 1027, "text": "One mutation, R367H, lies in the first P segment of the pore-lining region between the DIS5 and DIS6 transmembrane segments of SCN5A. A second mutation, A735V, lies in the first transmembrane segment of domain II (DIIS1) close to the first extracellular loop between DIIS1 and DIIS2, whereas the third mutation, R1192Q, lies in domain III.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11823453", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 397, "text": "The substitution (D1790G) causes LQTS and the insertion (D1795) induces both LQTS and Brugada syndromes in carrier patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11150514", "endSection": "abstract" } ] }, { "body": "What is Sotos syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25852445", "http://www.ncbi.nlm.nih.gov/pubmed/2347353", "http://www.ncbi.nlm.nih.gov/pubmed/12807965", "http://www.ncbi.nlm.nih.gov/pubmed/2319581", "http://www.ncbi.nlm.nih.gov/pubmed/22715272", "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "http://www.ncbi.nlm.nih.gov/pubmed/21484993", "http://www.ncbi.nlm.nih.gov/pubmed/16232326", "http://www.ncbi.nlm.nih.gov/pubmed/21834047", "http://www.ncbi.nlm.nih.gov/pubmed/26043501", "http://www.ncbi.nlm.nih.gov/pubmed/23239432" ], "ideal_answer": [ "Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability", "Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability." ], "type": "summary", "id": "571f30c40fd6f91b68000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26043501", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25852445", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 133, "text": "Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16232326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Sotos syndrome (OMIM #117550) is a congenital syndrome characterized by overgrowth with advanced bone age, macrocephaly, and learning difficulties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23239432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, and variable learning disabilities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21834047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Sotos syndrome is an overgrowth syndrome characterised by pre- and postnatal overgrowth, macrocephaly, advanced bone age, and typical facial features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12807965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Sotos syndrome is an autosomal dominant condition characterized by pre- and postnatal overgrowth (tall stature and macrocephaly), a typical facial appearance, advanced bone age, and developmental delay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21484993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Sotos syndrome is characterised by excessive pre and postnatal growth, a variable degree of learning difficulties and a recognisable facial appearance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22715272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Sotos' syndrome, or cerebral gigantism, is a disorder of growth regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2319581", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 184, "text": "Initial descriptions of Sotos syndrome included severe to mild mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2347353", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 489, "text": "Sotos syndrome is another genetic and neurodevelopmental syndrome that can be associated with autistic as well as communication and language disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2347353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16232326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Sotos syndrome (OMIM #117550) is a congenital syndrome characterized by overgrowth with advanced bone age, macrocephaly, and learning difficulties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23239432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, and variable learning disabilities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21834047", "endSection": "abstract" } ] }, { "body": "What is the CRAPome database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23921808" ], "ideal_answer": [ "The CRAPome is a contaminant repository for affinity purification-mass spectrometry data." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030562" ], "type": "summary", "id": "531e01ff267d7dd05300000e", "snippets": [ { "offsetInBeginSection": 938, "offsetInEndSection": 1004, "text": "the contaminant repository for affinity purification (the CRAPome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23921808", "endSection": "abstract" } ] }, { "body": "List all articles on network meta-analysis for smoking cessation", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23046909", "http://www.ncbi.nlm.nih.gov/pubmed/22992327", "http://www.ncbi.nlm.nih.gov/pubmed/19357145", "http://www.ncbi.nlm.nih.gov/pubmed/23728690", "http://www.ncbi.nlm.nih.gov/pubmed/24323793" ], "ideal_answer": [ "Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis.\nPharmacological interventions for smoking cessation: an overview and network meta-analysis\nEffectiveness and cost-effectiveness of computer and other electronic aids for smoking cessation: a systematic review and network meta-analysis.\nSmoking cessation interventions in COPD: a network meta-analysis of randomised trials." ], "exact_answer": [ [ "Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis." ], [ "Pharmacological interventions for smoking cessation: an overview and network meta-analysis" ], [ "Effectiveness and cost-effectiveness of computer and other electronic aids for smoking cessation: a systematic review and network meta-analysis." ], [ "Smoking cessation interventions in COPD: a network meta-analysis of randomised trials." ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017418", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016540" ], "type": "list", "id": "535d5bac7d100faa09000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24323793", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Pharmacological interventions for smoking cessation: an overview and network meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728690", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Effectiveness and cost-effectiveness of computer and other electronic aids for smoking cessation: a systematic review and network meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046909", "endSection": "title" }, { "offsetInBeginSection": 1395, "offsetInEndSection": 1481, "text": "network meta-analysis on interventions for smoking cessation including over 100 trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22992327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Smoking cessation interventions in COPD: a network meta-analysis of randomised trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19357145", "endSection": "title" } ] }, { "body": "Can RG7112 inhibit MDM2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "http://www.ncbi.nlm.nih.gov/pubmed/23808545", "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "http://www.ncbi.nlm.nih.gov/pubmed/23084521", "http://www.ncbi.nlm.nih.gov/pubmed/24869939", "http://www.ncbi.nlm.nih.gov/pubmed/24309210", "http://www.ncbi.nlm.nih.gov/pubmed/21391905", "http://www.ncbi.nlm.nih.gov/pubmed/25082860", "http://www.ncbi.nlm.nih.gov/pubmed/24812409" ], "ideal_answer": [ "Yes, RG7112 is a small molecule MDM2 antagonist." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/MDM2_DANRE", "http://www.uniprot.org/uniprot/MDM2_MOUSE", "http://www.uniprot.org/uniprot/MDM2_MESAU", "http://www.uniprot.org/uniprot/MDM2_CANLF", "http://www.uniprot.org/uniprot/MDM2_HUMAN", "http://www.uniprot.org/uniprot/MDM2_FELCA", "http://www.uniprot.org/uniprot/MDM2_XENLA" ], "type": "yesno", "id": "56ed08062ac5ed1459000005", "snippets": [ { "offsetInBeginSection": 86, "offsetInEndSection": 330, "text": "To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 723, "text": "RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 573, "text": "To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "title" }, { "offsetInBeginSection": 398, "offsetInEndSection": 477, "text": "RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23808545", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 568, "text": "RG7112 binds MDM2 with high affinity (K(D) ~ 11 nmol/L), blocking its interactions with p53 in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 864, "text": "The effects of RG7112 and Peg-IFN\u03b1 2a on MPN progenitor cells were dependent on blocking p53-MDM2 interactions and activating the p53 pathway, thereby increasing MPN CD34(+) cell apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon \u03b1 2a target JAK2V617F-positive progenitor and stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869939", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "In this issue of Blood, Lu et al describe the cooperation between an orally bioavailable mouse double minute 2 (MDM2) antagonist (RG7112) and the pegylated interferon \u03b1 (Peg-IFN\u03b1 2a) to target JAK2V617F hematopoietic progenitors and stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25082860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309210", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon \u03b1 2a target JAK2V617F-positive progenitor and stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869939", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "title" }, { "offsetInBeginSection": 614, "offsetInEndSection": 802, "text": "The primary endpoint was to assess markers of RG7112-dependent MDM2 inhibition and P53 pathway activation (P53, P21, MDM2, Ki-67, macrophage inhibitory cytokine-1 [MIC-1], and apoptosis). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 401, "text": "However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23808545", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 866, "text": "Treatment with low doses of RG7112, an orally available small-molecule inhibitor of p53-MDM2, both alone and combined with pegylated interferon \u03b1 2a (Peg-IFN\u03b1 2a), significantly decreased MPN colony-forming unit-granulocyte macrophage and burst-forming unit-erythroid numbers and preferentially eliminated the total number of JAKV617F(+) MPN hematopoietic progenitor cells. The effects of RG7112 and Peg-IFN\u03b1 2a on MPN progenitor cells were dependent on blocking p53-MDM2 interactions and activating the p53 pathway, thereby increasing MPN CD34(+) cell apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869939", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 807, "text": "RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "abstract" } ] }, { "body": "Which clotting factor is inhibited by betrixaban?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23876036", "http://www.ncbi.nlm.nih.gov/pubmed/21144965", "http://www.ncbi.nlm.nih.gov/pubmed/23298923", "http://www.ncbi.nlm.nih.gov/pubmed/22371104", "http://www.ncbi.nlm.nih.gov/pubmed/19132191", "http://www.ncbi.nlm.nih.gov/pubmed/23964817", "http://www.ncbi.nlm.nih.gov/pubmed/23557519", "http://www.ncbi.nlm.nih.gov/pubmed/22655676", "http://www.ncbi.nlm.nih.gov/pubmed/23547865", "http://www.ncbi.nlm.nih.gov/pubmed/23683607", "http://www.ncbi.nlm.nih.gov/pubmed/19601856", "http://www.ncbi.nlm.nih.gov/pubmed/23487517", "http://www.ncbi.nlm.nih.gov/pubmed/23086101", "http://www.ncbi.nlm.nih.gov/pubmed/24650612", "http://www.ncbi.nlm.nih.gov/pubmed/19996630", "http://www.ncbi.nlm.nih.gov/pubmed/21892216", "http://www.ncbi.nlm.nih.gov/pubmed/22742650", "http://www.ncbi.nlm.nih.gov/pubmed/23394539", "http://www.ncbi.nlm.nih.gov/pubmed/20124518", "http://www.ncbi.nlm.nih.gov/pubmed/22680641", "http://www.ncbi.nlm.nih.gov/pubmed/19739042", "http://www.ncbi.nlm.nih.gov/pubmed/19297154", "http://www.ncbi.nlm.nih.gov/pubmed/19644596", "http://www.ncbi.nlm.nih.gov/pubmed/24344662", "http://www.ncbi.nlm.nih.gov/pubmed/20520539", "http://www.ncbi.nlm.nih.gov/pubmed/21047577", "http://www.ncbi.nlm.nih.gov/pubmed/22564122" ], "ideal_answer": [ "Betrixaban is an orally administered direct clotting factor Xa inhibitor." ], "exact_answer": [ "Xa" ], "type": "factoid", "id": "55200c606b348bb82c000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Evaluation of the oral direct factor Xa inhibitor - betrixaban.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964817", "endSection": "title" }, { "offsetInBeginSection": 364, "offsetInEndSection": 552, "text": "Betrixaban , an orally administered direct factor Xa inhibitor, is entering a Phase III trial and undergoing investigation for similar indications as apixaban, dabigatran and rivaroxaban. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964817", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 565, "text": "Following the success of the direct thrombin and FXa inhibitors already in the market, new agents are being tested. These include AZD0837, betrixaban, letaxaban, darexaban, and LY517717.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23876036", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 842, "text": "Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23557519", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 628, "text": "They must be modified and standardized for the measurement of direct FXa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban and others). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23547865", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 224, "text": "Betrixaban is a novel oral factor Xa inhibitor administered once daily, mostly excreted unchanged in the bile and with low (17%) renal excretion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23487517", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 735, "text": " These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298923", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 842, "text": "Apixaban, rivaroxaban, endoxaban, and betrixaban are specific direct inhibitors of factor Xa, while dabigatran inhibits factor IIa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086101", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 402, "text": "The majority of the drugs in development belong to the class of direct factor Xa inhibitors (the -xabans). These include betrixaban, letaxaban, darexaban, eribaxaban, and LY517717.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22742650", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 992, "text": "Examples of direct factor Xa inhibitors include apixaban, rivaroxaban, otamixaban, betrixaban and edoxaban. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22680641", "endSection": "abstract" }, { "offsetInBeginSection": 1260, "offsetInEndSection": 1411, "text": "EXPERT OPINION: A large body of Phase II and Phase III data is now available for FXa inhibitors such as rivaroxaban, apixaban, edoxaban and betrixaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22655676", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1433, "text": "Another factor Xa inhibitor, edoxaban, is under evaluation in an ongoing phase III clinical trial and others such as AZD0837, betrixaban and darexaban are still in safety and tolerability phase II studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22564122", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 658, "text": "Apixaban, betrixaban, edoxaban, and rivaroxaban are small-molecule, selective inhibitors that directly and reversibly bind to the active site of factor Xa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371104", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 684, "text": "Novel oral anticoagulant drugs, the direct thrombin antagonist dabigatran and factor Xa inhibitors such as rivaroxaban, apixaban, edoxaban, and betrixaban are more predictable and convenient anticoagulants in comparison with warfarin, mainly because of the non-requirement of regular laboratory monitoring and dose adjustments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21892216", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 615, "text": "Recently developed anticoagulants include direct thrombin antagonists such as dabigatran or factor Xa inhibitors such as rivaroxaban, apixaban, betrixaban, and edoxaban. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21144965", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 755, "text": "Direct factor Xa inhibitors include rivaroxiban, which has shown promising results for VTE prophylaxis and is being studied for VTE treatment, as well as apixaban and betrixaban, which are at earlier stages of clinical validation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047577", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1350, "text": "Two direct factor Xa inhibitors are emerging from phase II trials (betrixaban and YM150) and three are being evaluated in phase III trials (apixaban, edoxaban, and rivaroxaban) for the prevention of stroke and systemic emboli in patients with atrial fibrillation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20520539", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 838, "text": "Apixaban, rivaroxaban, endoxaban, and betrixaban are specific direct inhibitors of factor Xa, while dabigatran inhibits factor IIa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "[Pharmacologic and clinical characteristics of direct inhibitors of factor Xa: rivaroxaban, apixaban, edoxaban and betrixaban].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650612", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19132191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19132191", "endSection": "title" }, { "offsetInBeginSection": 70, "offsetInEndSection": 216, "text": "Betrixaban is a novel oral factor Xa inhibitor administered once daily, mostly excreted unchanged in the bile and with low (17%) renal excretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23487517", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 924, "text": "Betrixaban is a new direct factor Xa inhibitor with distinct pharmacological characteristics, including a long half-life, minimal renal clearance and minimal hepatic metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24344662", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 1094, "text": "Novel anticoagulants in clinical testing include orally active direct factor II inhibitors [dabigatran etexilate (BIBR 1048), AZD0837)], parenteral direct factor II inhibitors (flovagatran sodium), orally active direct factor X inhibitors [rivaroxaban (BAY 59-7939), apixaban, betrixaban, YM150, DU-176b, LY-517717, GW813893, TAK-442, PD 0348292] and new parenteral FXa inhibitors [idraparinux, idrabiotaparinux (biotinilated idraparinux; SSR 126517), ultra-low-molecular-weight heparins (ULMWH: AVE5026, RO-14)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19601856", "endSection": "abstract" }, { "offsetInBeginSection": 878, "offsetInEndSection": 986, "text": "Examples of direct factor Xa inhibitors include apixaban, rivaroxaban, otamixaban, betrixaban and edoxaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22680641", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 535, "text": "Betrixaban , an orally administered direct factor Xa inhibitor, is entering a Phase III trial and undergoing investigation for similar indications as apixaban, dabigatran and rivaroxaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964817", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 439, "text": "Nowadays, four new inhibitors of factor Xa are used orally (rivaroxaban, apixaban, edoxaban, betrixaban), and they are at least as efficient as heparins and vitamin K antagonists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650612", "endSection": "abstract" }, { "offsetInBeginSection": 1558, "offsetInEndSection": 1745, "text": "Of interest, a factor Xa decoy, PRT4445, is currently under evaluation in conjunction with betrixaban, and may be a universal reversal agent for all anticoagulants with anti-Xa activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964817", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 619, "text": "Most are small synthetic molecules that target factor IIa (e.g., dabigatran etexilate, AZD-0837) or factor Xa (e.g., rivaroxaban, apixaban, betrixaban, DU176b, idrabiotaparinux).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19739042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297154", "endSection": "title" }, { "offsetInBeginSection": 323, "offsetInEndSection": 648, "text": "Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124518", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 655, "text": "Apixaban, betrixaban, edoxaban, and rivaroxaban are small-molecule, selective inhibitors that directly and reversibly bind to the active site of factor Xa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371104", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 732, "text": "These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298923", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 733, "text": "These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19132191", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 217, "text": "Betrixaban is a novel oral factor Xa inhibitor administered once daily, mostly excreted unchanged in the bile and with low (17%) renal excretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23487517", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 926, "text": "Betrixaban is a new direct factor Xa inhibitor with distinct pharmacological characteristics, including a long half-life, minimal renal clearance and minimal hepatic metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24344662", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 537, "text": "Betrixaban , an orally administered direct factor Xa inhibitor, is entering a Phase III trial and undergoing investigation for similar indications as apixaban, dabigatran and rivaroxaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964817", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 656, "text": "Apixaban, betrixaban, edoxaban, and rivaroxaban are small-molecule, selective inhibitors that directly and reversibly bind to the active site of factor Xa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371104", "endSection": "abstract" } ] }, { "body": "Which are the most frequent syndromes associated with inherited bone marrow failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16304365", "http://www.ncbi.nlm.nih.gov/pubmed/20022637" ], "ideal_answer": [ "The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders that share the inability of the bone marrow to produce an adequate number of blood cells. The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS) ", "The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders that share the inability of the bone marrow to produce an adequate number of blood cells. The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS)." ], "exact_answer": [ [ "Fanconi anemia" ], [ "Dyskeratosis congenita" ], [ "Diamond-Blackfan anemia" ], [ "Shwachman-Diamond syndrome" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001853", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001855", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019046", "http://www.disease-ontology.org/api/metadata/DOID:4961" ], "type": "list", "id": "55031270e9bde6963400001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Ocular and orbital manifestations of the inherited bone marrow failure syndromes: Fanconi anemia and dyskeratosis congenita", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20022637", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 349, "text": "The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders that share the inability of the bone marrow to produce an adequate number of blood cells. The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20022637", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 635, "text": "The major inherited bone marrow failure syndromes associated with development of pancytopenia include Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and amegakaryocytic thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16304365", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 634, "text": "The major inherited bone marrow failure syndromes associated with development of pancytopenia include Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and amegakaryocytic thrombocytopenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16304365", "endSection": "abstract" } ] }, { "body": "How is yellow fever virus transmitted?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20513550", "http://www.ncbi.nlm.nih.gov/pubmed/23697028", "http://www.ncbi.nlm.nih.gov/pubmed/21143108", "http://www.ncbi.nlm.nih.gov/pubmed/23411863", "http://www.ncbi.nlm.nih.gov/pubmed/21413253", "http://www.ncbi.nlm.nih.gov/pubmed/24056028", "http://www.ncbi.nlm.nih.gov/pubmed/23967358", "http://www.ncbi.nlm.nih.gov/pubmed/21199140", "http://www.ncbi.nlm.nih.gov/pubmed/23523817", "http://www.ncbi.nlm.nih.gov/pubmed/22999801", "http://www.ncbi.nlm.nih.gov/pubmed/21723310", "http://www.ncbi.nlm.nih.gov/pubmed/20874041", "http://www.ncbi.nlm.nih.gov/pubmed/16913829", "http://www.ncbi.nlm.nih.gov/pubmed/15705322", "http://www.ncbi.nlm.nih.gov/pubmed/22594140", "http://www.ncbi.nlm.nih.gov/pubmed/24027319", "http://www.ncbi.nlm.nih.gov/pubmed/18645665", "http://www.ncbi.nlm.nih.gov/pubmed/22264275", "http://www.ncbi.nlm.nih.gov/pubmed/23980723", "http://www.ncbi.nlm.nih.gov/pubmed/22377581", "http://www.ncbi.nlm.nih.gov/pubmed/22897918", "http://www.ncbi.nlm.nih.gov/pubmed/22966141", "http://www.ncbi.nlm.nih.gov/pubmed/23740065", "http://www.ncbi.nlm.nih.gov/pubmed/16707042", "http://www.ncbi.nlm.nih.gov/pubmed/23133693" ], "ideal_answer": [ "Yellow fever virus is transmitted by mosquitoes and is restricted to Africa, Central and South America and the Caribbean. \nYellow fever virus is a flavivirus, and there is only one antigenic type. It was taken to the Americas by the early slave traders, and nowadays reported in Africa, America, Asia and Europe. Yellow fever virus is transmitted by two different cycles: \n-from human to human by the mosquito Aedes aegypti; which is well-adapted to breeding around human habitations; the infection can be maintained in this way as \u2018urban\u2019 yellow fever.\n-from infected monkeys to humans by mosquitoes such as Haemagogus. This is \u2018jungle\u2019 yellow fever and is seen in Africa and South America.\n\nYellow fever is not transmitted directly from human to human by day-to-day contact, but transmission from ill patients to healthcare workers has been reported, notably after needlestick injury." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:9682", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015004", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015005" ], "type": "summary", "id": "533aaab6d6d3ac6a34000062", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 472, "text": "Yellow Fever (YF) is an acute viral communicable disease transmitted by an arbovirus of the flavivirus genus. It is primarily a zoonotic disease, especially the monkeys. Worldwide, an estimated 200\u2009000 cases of yellow fever occurred each year, and the case-fatality rate is ~15%. Forty-five endemic countries in Africa and Latin America, with a population of close to 1 billion, are at risk. Up to 50% of severely affected persons from YF die without treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056028", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 565, "text": "yellow fever virus (YFV) are transmitted between arthropod vectors and vertebrate hosts. While barriers limiting arbovirus population diversity have been observed in mosquitoes, whether barriers exist in vertebrate hosts is unclear. To investigate whether arboviruses encounter bottlenecks during dissemination in the vertebrate host, we infected immunocompetent mice and immune-deficient mice lacking alpha/beta interferon (IFN-\u03b1/\u03b2) receptors (IFNAR\u207b/\u207b mice) with a pool of genetically marked viruses to evaluate dissemination and host barriers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24027319", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 190, "text": "Re-emergence of vector-borne diseases such as dengue and yellow fever, which are both transmitted by the Aedes aegypti mosquito, has been correlated with insecticide resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23980723", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 393, "text": "Arthropod-borne viruses are important emerging pathogens world-wide. Viruses transmitted by mosquitoes, such as dengue, yellow fever, and Japanese encephalitis viruses, infect hundreds of millions of people and animals each year. Global surveillance of these viruses in mosquito vectors using molecular based assays is critical for prevention and control of the associated diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23967358", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 489, "text": "fever and dengue fever are mosquito-borne infectious diseases transmitted by Aedes aegyptii, the presence of yellow fever in Sudan and dengue fever in Saudi Arabia are threats to Egypt with the reemerging of Ae. aegyptii in Southern Egypt, larvae control is feasible than flying adults", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23697028", "endSection": "abstract" }, { "offsetInBeginSection": 39, "offsetInEndSection": 282, "text": "dengue virus (DENV) and yellow fever virus (YFV), that originated in sylvatic cycles maintained in non-human primates and forest-dwelling mosquitoes have emerged repeatedly into sustained human-to-human transmission by Aedes aegypti mosquitoes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523817", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 439, "text": "Sylvatic cycles of both viruses remain active, and where the two viruses overlap in West Africa they utilize similar suites of monkeys and Aedes mosquitoes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523817", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 1098, "text": "First, the sylvatic cycle of YFV originated in Africa and was introduced into the New World, probably as a result of the slave trade, but is absent in Asia; in contrast, sylvatic DENV likely originated in Asia and has spread to Africa but not to the New World. Second, while sylvatic YFV can emerge into extensive urban outbreaks in humans, these invariably die out, whereas four different types of DENV have established human transmission cycles that are ecologically and evolutionarily distinct from their sylvatic ancestors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523817", "endSection": "abstract" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1358, "text": "Finally, transmission of YFV among humans has been documented only in Africa and the Americas, whereas DENV is transmitted among humans across most of the range of competent Aedes vectors, which in the last decade has included every continent save Antarctica", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523817", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 237, "text": "Mosquito-transmitted diseases such as malaria, dengue, yellow fever and filariasis are the main contributors to this burden", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411863", "endSection": "abstract" }, { "offsetInBeginSection": 67, "offsetInEndSection": 272, "text": "yellow fever (YFV) viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133693", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 202, "text": "The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22966141", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 540, "text": "The causative agent of yellow fever is an arbovirus of the Flaviviridae family transmitted by infected Aedes mosquitoes, particularly in Africa. In the Central African Republic since 2006, cases have been notified in the provinces of Ombella-Mpoko, Ouham-Pende, Basse-Kotto, Haute-Kotto and in Bangui the capital. As the presence of a vector of yellow fever virus (YFV) represents a risk for spread of the disease, we undertook entomological investigations at these sites to identify potential vectors of YFV and their abundance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22897918", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 203, "text": " family Flaviviridae, includes a number of important arthropod-transmitted human pathogens such as dengue viruses, West Nile virus, Japanese encephalitis virus and yellow fever virus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22377581", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 948, "text": "Reports of the detection of these viruses with no recognized pathogenic role in humans are increasing in mosquitoes collected around the world, particularly in those sampled in entomological surveys targeting pathogenic flaviviruses. The presence of six potential flaviviruses, detected from independent European arbovirus surveys undertaken in the Czech Republic, Italy, Portugal, Spain and the UK between 2007 and 2010, is reported in this work", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22377581", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 416, "text": "Yellow Fever virus (YFV) is an important arboviral pathogen in much of sub-Saharan Africa and the tropical Americas. It is the prototype member of the genus Flavivirus and is transmitted primarily by Aedes (Stegomyia) mosquitoes. The incidence of human infections in endemic areas has risen in recent years. Prompt and dependable identification of YFV is a critical component of response to suspect cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22264275", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 358, "text": "Health-care professionals can help travelers by providing accurate pre-travel counseling for mosquito-transmitted diseases such as malaria, yellow fever, and dengue fever. Governments and international organizations will benefit from knowledge survey among health professionals in this field to promote the development of travel health profession", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199140", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 165, "text": "United States made 12 million visits to developing countries in Asia, South America, Central America, Oceania, the Middle East, and Africa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20874041", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 223, "text": " Yellow fever is a serious illness public health importance and is transmitted by mosquitoes of the genera Haemagogus and Sabethes in the rural and forest environments, and by Aedes aegypti in the urban setting", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18645665", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 919, "text": "Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22966141", "endSection": "abstract" } ] }, { "body": "Are there any specific antidotes for dabigatran?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22615265", "http://www.ncbi.nlm.nih.gov/pubmed/23389753", "http://www.ncbi.nlm.nih.gov/pubmed/23312927", "http://www.ncbi.nlm.nih.gov/pubmed/21748501", "http://www.ncbi.nlm.nih.gov/pubmed/23821689", "http://www.ncbi.nlm.nih.gov/pubmed/24103671", "http://www.ncbi.nlm.nih.gov/pubmed/23634730", "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "http://www.ncbi.nlm.nih.gov/pubmed/20352166", "http://www.ncbi.nlm.nih.gov/pubmed/23953907", "http://www.ncbi.nlm.nih.gov/pubmed/20858186", "http://www.ncbi.nlm.nih.gov/pubmed/22308807", "http://www.ncbi.nlm.nih.gov/pubmed/23810130", "http://www.ncbi.nlm.nih.gov/pubmed/23460104", "http://www.ncbi.nlm.nih.gov/pubmed/23657589", "http://www.ncbi.nlm.nih.gov/pubmed/22353706", "http://www.ncbi.nlm.nih.gov/pubmed/23790307", "http://www.ncbi.nlm.nih.gov/pubmed/22008738", "http://www.ncbi.nlm.nih.gov/pubmed/22669799" ], "ideal_answer": [ "No specific antidote currently exists for dabigatran" ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000931", "http://www.biosemantics.org/jochem#4242811" ], "type": "yesno", "id": "532f08dcd6d3ac6a3400002a", "snippets": [ { "offsetInBeginSection": 172, "offsetInEndSection": 491, "text": "Novel oral anticoagulants (NOACs)--apixaban, dabigatran, and rivaroxaban--have a significantly smaller risk of intracerebral hemorrhage (ICH). However, two facts make this situation complicated: First, the risk of hematoma expansion is unknown for NOACs. Second, there is no specific antidote for neither of the NOACs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24103671", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 413, "text": "However, many physicians are wary of these drugs, since there is limited evidence on how to manage bleeding in patients taking them, and since no specific antidote is known to reverse their anticoagulant effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821689", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 592, "text": "Given the absence of a specific antidote, the action to be taken in these situations must be defined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810130", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1175, "text": "The fact that there is no specific antidote to reverse the anticoagulant action of the new anticoagulants can impair management of hemorrhagic complications;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23790307", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 537, "text": "Unlike the vitamin K antagonist, i.e. warfarin, there is no specific antidote for these medications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23657589", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 342, "text": "The lack of guidelines, protocols, and an established specific antidote to reverse the anticoagulation effect of dabigatran potentially increases the rates of morbidity and mortality in patients with closed head injury (CHI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23634730", "endSection": "abstract" }, { "offsetInBeginSection": 921, "offsetInEndSection": 1599, "text": "The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa\u00ae), rivaroxaban (Xarelto\u00ae) and apixaban (Eliquis\u00ae), also known as \"direct\" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23460104", "endSection": "abstract" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1741, "text": "NOA also have other unresolved problems: drug interactions are still possible, specific coagulation test to assess them must be developed, and no specific antidote is currently available in case of hemorrhagic complication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312927", "endSection": "abstract" }, { "offsetInBeginSection": 1648, "offsetInEndSection": 1812, "text": " It is critical to identify and subsequently manage dabigatran etexilate toxicity because there is no specific antidote to reverse the drug's anticoagulant effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22669799", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 473, "text": "In the absence of a specific antidote for this novel oral anticoagulant medication, even in an emergency situation, successful surgical treatment was possible with an aggressive use of available prohaemostatic agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22615265", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 957, "text": "While these trial data are extremely encouraging, several practical issues (e.g., lack of specific antidote, safety of long-term treatment or cost-effectiveness in \"real-life\" clinical practice) still need to be elucidated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22353706", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 661, "text": "In case of massive bleeding, management is unclear and none of these newer agents has a specific antidote that completely reverses its anticoagulant effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22308807", "endSection": "abstract" }, { "offsetInBeginSection": 1935, "offsetInEndSection": 2044, "text": "The short half-life of these new agents compensates for the lack of any specific antidote in many instances. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177763", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1354, "text": "As there is no specific antidote, the only treatment option is discontinuation of the drug and supportive management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21748501", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 750, "text": "Currently, none of these new agents has a specific antidote, and little advise can be given on how to manage a major bleeding event.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20858186", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1609, "text": "Although there is no specific antidote to antagonise the anticoagulant effect of dabigatran, due to its short duration of effect drug discontinuation is usually sufficient to reverse any excessive anticoagulant activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20352166", "endSection": "abstract" } ] }, { "body": "What is the outcome of TAF10 interacting with the GATA1 transcription factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25870109" ], "ideal_answer": [ "TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis." ], "exact_answer": [ "Control of Mouse Erythropoiesis" ], "concepts": [ "http://www.uniprot.org/uniprot/GATA1_HUMAN", "http://www.uniprot.org/uniprot/TAF10_HUMAN", "http://www.uniprot.org/uniprot/GAT1A_XENLA", "http://www.uniprot.org/uniprot/GATA1_ARATH", "http://www.uniprot.org/uniprot/TAF10_YEAST", "http://www.uniprot.org/uniprot/TAF10_ARATH", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050982", "http://www.uniprot.org/uniprot/GATA1_CHICK" ], "type": "factoid", "id": "56a8b8b5a17756b72f000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25870109", "endSection": "title" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1235, "text": "we show that TAF10 interacts directly with GATA1 and that TAF10 is enriched on the GATA1 locus in human fetal erythroid cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25870109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25870109", "endSection": "title" } ] }, { "body": "How does TNF affect thyroid hormone receptors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18403482" ], "ideal_answer": [ "TNF-alpha inhibits the T3-induced expression of thyroid hormone receptor-beta" ], "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.biosemantics.org/jochem#4243664", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/TNFA_RABIT", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "summary", "id": "516d5bc5298dcd4e51000079", "snippets": [ { "offsetInBeginSection": 1279, "offsetInEndSection": 1480, "text": "treatment of the cells with T(3) for 2 d induced the expression of thyroid hormone receptor-beta and caspase-3, and this thyroid hormone receptor-beta induction was drastically repressed by xTNF-alpha.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18403482", "endSection": "sections.0" } ] }, { "body": "Which ones are the ESKAPE organisms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22366995", "http://www.ncbi.nlm.nih.gov/pubmed/25124187", "http://www.ncbi.nlm.nih.gov/pubmed/24342634", "http://www.ncbi.nlm.nih.gov/pubmed/26139286", "http://www.ncbi.nlm.nih.gov/pubmed/21659436", "http://www.ncbi.nlm.nih.gov/pubmed/23548324", "http://www.ncbi.nlm.nih.gov/pubmed/24794971", "http://www.ncbi.nlm.nih.gov/pubmed/25232168", "http://www.ncbi.nlm.nih.gov/pubmed/24392752", "http://www.ncbi.nlm.nih.gov/pubmed/25498089", "http://www.ncbi.nlm.nih.gov/pubmed/23267668" ], "ideal_answer": [ "The 6 ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species." ], "exact_answer": [ [ "Enterococcus faecium" ], [ "Staphylococcus aureus" ], [ "Klebsiella pneumoniae" ], [ "Acinetobacter baumannii" ], [ "Pseudomonas aeruginosa" ], [ "Enterobacter species" ] ], "type": "list", "id": "56d2ac03f22319765a000004", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 313, "text": "The aim of this study was to test in the clinic whether antimicrobial diversity affects resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens in ventilator-associated pneumonia (VAP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21659436", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 298, "text": "Despite important geographical variations, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (ESKAPE) pathogens constitute more than 80% of ventilator-associated pneumonia (VAP) episodes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22366995", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 375, "text": "Multidrug resistance among the 'ESKAPE' organisms - encompassing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - is of particular concern because they are responsible for many serious infections in hospitals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26139286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which include A. baumannii (the ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24342634", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 374, "text": "'ESKAPE' (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acintobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens play a major role in the rapidly changing scenario of antimicrobial resistance in the 21st century.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392752", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 337, "text": "Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted as a serious complication in solid organ transplant (SOT), more information is urgently needed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25124187", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 478, "text": "Multidrug resistance among the 'ESKAPE' organisms - encompassing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26139286", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 376, "text": "Multidrug resistance among the 'ESKAPE' organisms - encompassing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - is of particular concern because they are responsible for many serious infections in hospitals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26139286", "endSection": "abstract" } ] }, { "body": "What is the effect of dovitinib on the cell cycle?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22027573", "http://www.ncbi.nlm.nih.gov/pubmed/21521775", "http://www.ncbi.nlm.nih.gov/pubmed/24238094" ], "ideal_answer": [ "Dovitinib triggers a G2 /M arrest. It promotes a delay in mitotic exit in a subset of cells, causing the cells to undergo mitotic slippage. Higher concentrations of Dovitinib induce a G2 arrest similar to the G2 DNA damage checkpoint." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0007050" ], "type": "summary", "id": "56d046813975bb303a00000f", "snippets": [ { "offsetInBeginSection": 128, "offsetInEndSection": 520, "text": "Dovitinib triggered a G2 /M arrest in cancer cell lines from diverse origins including HeLa, nasopharyngeal carcinoma, and hepatocellular carcinoma. Single-cell analysis revealed that Dovitinib promoted a delay in mitotic exit in a subset of cells, causing the cells to undergo mitotic slippage. Higher concentrations of Dovitinib induced a G2 arrest similar to the G2 DNA damage checkpoint. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24238094", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1038, "text": "Finally, Dovitinib-mediated G2 cell cycle arrest and subsequent cell death could be promoted after DNA damage repair was disrupted by inhibitors of poly(ADP-ribose) polymerases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24238094", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 887, "text": "Treatment of SK-HEP1 cells with dovitinib resulted in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027573", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1207, "text": "Finally, Dovitinib-mediated G2 cell cycle arrest and subsequent cell death could be promoted after DNA damage repair was disrupted by inhibitors of poly(ADP-ribose) polymerases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24238094", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1340, "text": "Inhibition of FGFR3 with dovitinib decreased cell survival, increased apoptosis, and induced cell cycle arrest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21521775", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 890, "text": "RESULTS: Treatment of SK-HEP1 cells with dovitinib resulted in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027573", "endSection": "abstract" } ] }, { "body": "What is the involvement of PDGFRB in metastatic medulloblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19417143" ], "ideal_answer": [ "Platelet-derived growth factor (PDGF) receptor B (PDGFRB) expression was shown to correlate with metastatic medulloblastoma, while PDGFRB tyrosine kinase activity was demonstrated to be critical for migration and invasion of medulloblastoma cells possibly by transactivating EGFR." ], "concepts": [ "http://www.uniprot.org/uniprot/PGFRB_TAKRU", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020797", "http://www.disease-ontology.org/api/metadata/DOID:3858" ], "type": "summary", "id": "55391b2cbc4f83e828000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Imatinib blocks migration and invasion of medulloblastoma cells by concurrently inhibiting activation of platelet-derived growth factor receptor and transactivation of epidermal growth factor receptor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417143", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Platelet-derived growth factor (PDGF) receptor (PDGFR) expression correlates with metastatic medulloblastoma. PDGF stimulation of medulloblastoma cells phosphorylates extracellular signal-regulated kinase (ERK) and promotes migration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417143", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1900, "text": "Imatinib (1 \u03bcmol/L) treatment of DAOY and D556 cells inhibited PDGF-BB- and serum-mediated migration and invasion at 24 and 48 h, respectively, and concomitantly inhibited PDGF-BB activation of PDGFRB, Akt, and ERK but increased PTEN expression and activity. Imatinib treatment also induced DAOY cell apoptosis at 72 h and inhibited DAOY and D556 cell proliferation at 48 h. siRNA silencing of PDGFRB similarly inhibited signaling, migration, and survival and both siRNA and imatinib treatment inhibited PDGF-BB-mediated EGFR transactivation, indicating that the effects of imatinib treatment are specific to PDGFRB target inhibition. These results indicate that PDGFRB tyrosine kinase activity is critical for migration and invasion of medulloblastoma cells possibly by transactivating EGFR; thus, imatinib may represent an important novel therapeutic agent for the treatment of medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417143", "endSection": "abstract" }, { "offsetInBeginSection": 1629, "offsetInEndSection": 1891, "text": "These results indicate that PDGFRB tyrosine kinase activity is critical for migration and invasion of medulloblastoma cells possibly by transactivating EGFR; thus, imatinib may represent an important novel therapeutic agent for the treatment of medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417143", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1900, "text": "These results indicate that PDGFRB tyrosine kinase activity is critical for migration and invasion of medulloblastoma cells possibly by transactivating EGFR; thus, imatinib may represent an important novel therapeutic agent for the treatment of medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417143", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1899, "text": "These results indicate that PDGFRB tyrosine kinase activity is critical for migration and invasion of medulloblastoma cells possibly by transactivating EGFR; thus, imatinib may represent an important novel therapeutic agent for the treatment of medulloblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19417143", "endSection": "abstract" } ] }, { "body": "What is known as Calcium Induced Calcium Release (CICR) and its role in cardiomyocyte contractility?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15110149", "http://www.ncbi.nlm.nih.gov/pubmed/23123322", "http://www.ncbi.nlm.nih.gov/pubmed/2726431", "http://www.ncbi.nlm.nih.gov/pubmed/21718716", "http://www.ncbi.nlm.nih.gov/pubmed/18538346", "http://www.ncbi.nlm.nih.gov/pubmed/25377479", "http://www.ncbi.nlm.nih.gov/pubmed/21979103", "http://www.ncbi.nlm.nih.gov/pubmed/17214508", "http://www.ncbi.nlm.nih.gov/pubmed/15194743", "http://www.ncbi.nlm.nih.gov/pubmed/10779321" ], "ideal_answer": [ "the cicr mechanism has been understood mainly based on binding of cytosolic ca(2+) with ryanodine receptors (ryrs) and inducing ca(2+) release from the sarcoplasmic reticulum (sr). l-type ca(2+) channels activate ryrs to produce cicr in smooth muscle cells in the form of ca(2+) sparks and propagated ca(2+) waves. in heart cells, a tight coupling between the gating of single l-type ca(2+) channels and ryanodine receptors (ryrs) underlies calcium release. the importance of ca-induced ca release in excitation-contraction coupling in the heart. waves of calcium-induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias. in mammals, ca(2+) influx as l-type ca(2+) current (ica) triggers the release of ca(2+) from sarcoplasmic reticulum (sr) and ca(2+)-induced ca(2+) release (cicr) is critical for excitation-contraction coupling. ", "Cardiomyocyte contraction depends on rapid changes in intracellular Ca(2+). Ca(2+) influx as L-type Ca(2+) current (ICa) triggers the release of Ca(2+) from sarcoplasmic reticulum (SR) and Ca(2+)-induced Ca(2+) release (CICR) is critical for excitation-contraction coupling. Calcium-induced calcium-release in cardiac myocytes takes place in spatially restricted regions known as dyads, where discrete patches of junctional sarcoplasmic reticulum tightly associate with the t-tubule membrane. Calcium-induced calcium release (CICR) has been observed in cardiac myocytes as elementary calcium release events (calcium sparks) associated with the opening of L-type Ca(2+) channels. Waves of calcium-induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias." ], "concepts": [ "http://www.biosemantics.org/jochem#4277675" ], "type": "summary", "id": "54dc8ed6c0bb8dce23000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Cardiomyocyte contraction depends on rapid changes in intracellular Ca(2+). In mammals, Ca(2+) influx as L-type Ca(2+) current (ICa) triggers the release of Ca(2+) from sarcoplasmic reticulum (SR) and Ca(2+)-induced Ca(2+) release (CICR) is critical for excitation-contraction coupling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25377479", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 291, "text": "Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "It is well known that calcium-induced calcium-release in cardiac myocytes takes place in spatially restricted regions known as dyads, where discrete patches of junctional sarcoplasmic reticulum tightly associate with the t-tubule membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21718716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Calcium (Ca(2+))-induced Ca(2+) release (CICR) is widely accepted as the principal mechanism linking electrical excitation and mechanical contraction in cardiac cells. The CICR mechanism has been understood mainly based on binding of cytosolic Ca(2+) with ryanodine receptors (RyRs) and inducing Ca(2+) release from the sarcoplasmic reticulum (SR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18538346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Waves of calcium-induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15194743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Calcium-induced calcium release (CICR) has been observed in cardiac myocytes as elementary calcium release events (calcium sparks) associated with the opening of L-type Ca(2+) channels. In heart cells, a tight coupling between the gating of single L-type Ca(2+) channels and ryanodine receptors (RYRs) underlies calcium release. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10779321", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 487, "text": "L-type Ca(2+) channels activate RYRs to produce CICR in smooth muscle cells in the form of Ca(2+) sparks and propagated Ca(2+) waves.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10779321", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 587, "text": " the importance of Ca-induced Ca release in excitation-contraction coupling in the heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2726431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Calcium-induced calcium release (CICR) is an inherently regenerative process due to the Ca(2+)-dependent gating of ryanodine receptors (RyRs) in the sarco/endoplasmic reticulum (SR) and is critical for cardiac excitation-contraction coupling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "PURPOSE: Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21979103", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 249, "text": "The Ca(2+)-induced Ca(2+) release (CICR) process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17214508", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 247, "text": "The Ca(2+)-induced Ca(2+) release (CICR) process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17214508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "The majority of contractile calcium in cardiac muscle is released from stores in the sarcoplasmic reticulum (SR), by a process of calcium-induced calcium release (CICR) through ryanodine receptors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15110149", "endSection": "abstract" } ] }, { "body": "What is the action of molindone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7656507", "http://www.ncbi.nlm.nih.gov/pubmed/9353417", "http://www.ncbi.nlm.nih.gov/pubmed/9577836", "http://www.ncbi.nlm.nih.gov/pubmed/6249092", "http://www.ncbi.nlm.nih.gov/pubmed/1224004", "http://www.ncbi.nlm.nih.gov/pubmed/6817377", "http://www.ncbi.nlm.nih.gov/pubmed/7965768", "http://www.ncbi.nlm.nih.gov/pubmed/2895008" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17796303", "o": "T43.505" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17796303", "o": "Adverse effect of unspecified antipsychotics and neuroleptics" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2878520", "o": "http://linkedlifedata.com/resource/umls/label/A17796303" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17860102", "o": "T43.595" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2878546", "o": "http://linkedlifedata.com/resource/umls/label/A17860102" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17860102", "o": "Adverse effect of other antipsychotics and neuroleptics" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17809244", "o": "T43.595S" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2878549", "o": "http://linkedlifedata.com/resource/umls/label/A17809244" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17809244", "o": "Adverse effect of other antipsychotics and neuroleptics, sequela" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17809238", "o": "T43.505S" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17809238", "o": "Adverse effect of unspecified antipsychotics and neuroleptics, sequela" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2878523", "o": "http://linkedlifedata.com/resource/umls/label/A17809238" } ], "ideal_answer": [ "Molindone is a short-acting antipsychotic.\nMolindone, along with other antipsychotic drugs which elicit little or no Parkinsonism, bind more loosely than dopamine to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.\nMolindone is D2-selective in vitro and has a dual D1-D2 receptor profile in vivo.\nMolindone can selectively block the presynaptic DA receptors.\nMolindone causes a statistically significant up-regulation of both the long and short isoforms of the D2 receptor mRNAs in the prefrontal and temporal cortex, but has no effect on D4 mRNA levels in either cortical or striatal tissue.\nMolindone elevates Fos-like immunoreactivity (FLI) in the dorsolateral striatum.\nMolindone exhibits selectivity for cortical serotonin-stimulated cyclase versus dopamine-stimulated cyclase.\nMolindone in low intravenous doses (0.4-0.8 mg/kg) was found to reverse d-amphetamine and apomorphine induced depression of DA neurons and to block apomorphine induced depression of these cells. Molindone was also found to increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfacotry tubercles. In all of these respects molindone behaves identically to most classical neuroleptics. However, unlike most antipsychotic drugs previously tested, molindone failed to increase the baseline firing rate of DA cells and blocked haloperidol induced increases in DA neuron activity. In this regard molindone most closely resembles thioridazine and clozapine." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042493", "http://www.biosemantics.org/jochem#4066301", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008972", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064420", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097332", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014150", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228", "http://www.biosemantics.org/jochem#4249624" ], "type": "summary", "id": "52bf1f5f03868f1b06000017", "snippets": [ { "offsetInBeginSection": 1700, "offsetInEndSection": 2492, "text": "As determined by the new dissociation constants, antipsychotic drugs which elicit Parkinsonism (trifluperazine, chlorpromazine, raclopride, haloperidol, fluphenazine, risperidone) bind more tightly than dopamine to D2, while those antipsychotic drugs which elicit little or no Parkinsonism (melperone, seroquel, perlapine, clozapine, remoxipride, molindone, sulpiride, olanzapine, sertindole) bind more loosely than dopamine to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9577836", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 704, "text": "All antipsychotic drug treatments examined in this study caused a statistically significant up-regulation of both the long and short isoforms of the D2 receptor mRNAs in the prefrontal and temporal cortex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9353417", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1450, "text": "Other drugs of the typical (molindone and pimozide) and atypical (remoxipride) classes had no effect on D4 mRNA levels in either cortical or striatal tissue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9353417", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 779, "text": " Loxapine is an alternative when sedation is necessary and molindone is useful if a short-acting antipsychotic is required. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7656507", "endSection": "abstract" }, { "offsetInBeginSection": 1334, "offsetInEndSection": 1563, "text": "Neuroleptics with a clearly documented liability for producing extrapyramidal side effects (EPS) such as chlorpromazine, fluphenazine, haloperidol, loxapine, metoclopramide and molindone elevated FLI in the dorsolateral striatum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7965768", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 743, "text": "Pretreatment with molindone (0.45 and 0.8 mg/kg IP), in doses reported to selectively block the presynaptic DA receptors, not only decreased the cataleptic effect of AP but also reversed the AP antagonism of methamphetamine stereotypy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6817377", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 603, "text": " The antagonist molindone exhibits selectivity for cortical serotonin-stimulated cyclase versus dopamine-stimulated cyclase and may prove useful for further elucidating the sites of lisuride action. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6249092", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 928, "text": "Molindone in low intravenous doses (0.4-0.8 mg/kg) was found to reverse d-amphetamine and apomorphine induced depression of DA neurons and to block apomorphine induced depression of these cells. Molindone was also found to increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfacotry tubercles. In all of these respects molindone behaves identically to most classical neuroleptics. However, unlike most antipsychotic drugs previously tested, molindone failed to increase the baseline firing rate of DA cells and blocked haloperidol induced increases in DA neuron activity. In this regard molindone most closely resembles thioridazine and clozapine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1224004", "endSection": "abstract" } ] }, { "body": "What is the function of the enzymes known as dual specificity phoshpatases (DUSPs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22812510", "http://www.ncbi.nlm.nih.gov/pubmed/21764456", "http://www.ncbi.nlm.nih.gov/pubmed/21300429", "http://www.ncbi.nlm.nih.gov/pubmed/21288197", "http://www.ncbi.nlm.nih.gov/pubmed/22266315", "http://www.ncbi.nlm.nih.gov/pubmed/24311790", "http://www.ncbi.nlm.nih.gov/pubmed/24155099", "http://www.ncbi.nlm.nih.gov/pubmed/22769588", "http://www.ncbi.nlm.nih.gov/pubmed/23190643", "http://www.ncbi.nlm.nih.gov/pubmed/23926106", "http://www.ncbi.nlm.nih.gov/pubmed/19228121", "http://www.ncbi.nlm.nih.gov/pubmed/24308939", "http://www.ncbi.nlm.nih.gov/pubmed/24206177", "http://www.ncbi.nlm.nih.gov/pubmed/24531476" ], "ideal_answer": [ "DUSPs (dual-specificity phosphatases) are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. DUSPs have been implicated as major modulators of critical signalling pathways that are dysregulated in various diseases. DUSPs can be divided into six subgroups on the basis of sequence similarity that include slingshots, PRLs (phosphatases of regenerating liver), Cdc14 phosphatases (Cdc is cell division cycle), PTENs (phosphatase and tensin homologues deleted on chromosome 10), myotubularins, MKPs (mitogen-activated protein kinase phosphatases) and atypical DUSPs.", "Dual-specificity protein phosphatases participate in signal transduction pathways inactivating mitogen-activated protein kinases (MAP kinases). \nDual-specificity phosphatases (DUSPs) dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine residues on target MAPKs. \nThese signaling pathways are of critical importance in the regulation of numerous biological processes, including cell proliferation, differentiation and development." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054638", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054637", "http://www.uniprot.org/uniprot/PTP3_CHLMO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008138", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054642", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054640", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054641", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003674", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0017017" ], "type": "summary", "id": "5518e7a7622b194345000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "MAPK activity is negatively regulated by members of the dual specificity phosphatase (Dusp) family, which differ in expression, substrate specificity, and subcellular localization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311790", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 333, "text": "Dual-specificity phosphatases (DUSPs) dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine residues on target MAPKs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24308939", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 340, "text": " The dual-specificity phosphatases (DUSPs) constitute a heterogeneous group of cysteine-based protein tyrosine phosphatases, whose members exert a pivotal role in cell physiology by dephosphorylation of phosphoserine, phosphothreonine, and phosphotyrosine residues from proteins, as well as other non-proteinaceous substrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24206177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Dual-specificity MAP kinase phosphatases (MKPs) provide a complex negative regulatory network that acts to shape the duration, magnitude and spatiotemporal profile of MAP kinase activities in response to both physiological and pathological stimuli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22812510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 409, "text": "Dual-specificity phosphatases (DUSPs) is an emerging subclass of the protein tyrosine phosphatase gene superfamily, a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. Recently, a series of investigations of DUSPs defined their essential roles in cell proliferation, cancer and the immune response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Mitogen-activated protein kinases (MAPKs) fulfill essential biological functions and are key pharmaceutical targets. Regulation of MAPKs is achieved via a plethora of regulatory proteins including activating MAPKKs and an abundance of deactivating phosphatases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23926106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "The protein tyrosine phosphatase family (PTP) contains a group of dual-specificity phosphatases (DUSPs) that regulate the activivity of MAP kinases (MAPKs), which are key effectors in the control of cell growth and survival in physiological and pathological processes, including cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Dual-specificity protein phosphatases participate in signal transduction pathways inactivating mitogen-activated protein kinases (MAP kinases). These signaling pathways are of critical importance in the regulation of numerous biological processes, including cell proliferation, differentiation and development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Dual specificity phosphatase 1 (DUSP1) dephosphorylates and, hence, regulates the activity of MAP kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "Dual-Specificity Phosphatases (DUSPs) are enzymes that remove phosphate groups from both phospho-tyrosine and phospho-serine/threonine residues. A subgroup of DUSPs specifically targets Mitogen-Activated Protein Kinases (MAPKs) and has been shown to participate in the regulation of differential cellular responses to the large variety of stimuli conveyed by MAPK-pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 674, "text": "DUSPs (dual-specificity phosphatases) are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. DUSPs have been implicated as major modulators of critical signalling pathways that are dysregulated in various diseases. DUSPs can be divided into six subgroups on the basis of sequence similarity that include slingshots, PRLs (phosphatases of regenerating liver), Cdc14 phosphatases (Cdc is cell division cycle), PTENs (phosphatase and tensin homologues deleted on chromosome 10), myotubularins, MKPs (mitogen-activated protein kinase phosphatases) and atypical DUSPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19228121", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 339, "text": "The dual-specificity phosphatases (DUSPs) constitute a heterogeneous group of cysteine-based protein tyrosine phosphatases, whose members exert a pivotal role in cell physiology by dephosphorylation of phosphoserine, phosphothreonine, and phosphotyrosine residues from proteins, as well as other non-proteinaceous substrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24206177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Dual-specificity protein phosphatases (DUSPs), which dephosphorylate both phosphoserine/threonine and phosphotyrosine, play vital roles in immune activation, brain function and cell-growth signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24531476", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 332, "text": "Dual-specificity phosphatases (DUSPs), whose family currently contains 25 members, are phosphatases that can dephosphorylate both tyrosine and serine/threonine residues of their substrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22769588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "DUSPs (dual-specificity phosphatases) are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19228121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Dual-Specificity Phosphatases (DUSPs) are enzymes that remove phosphate groups from both phospho-tyrosine and phospho-serine/threonine residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Dual-specificity protein phosphatases (DUSPs), which dephosphorylate both phosphoserine/threonine and phosphotyrosine, play vital roles in immune activation, brain function and cell-growth signalling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24531476", "endSection": "abstract" } ] }, { "body": "How is bladder wall thickness measured?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17445666", "http://www.ncbi.nlm.nih.gov/pubmed/11490298", "http://www.ncbi.nlm.nih.gov/pubmed/20432327", "http://www.ncbi.nlm.nih.gov/pubmed/20438565", "http://www.ncbi.nlm.nih.gov/pubmed/18335255", "http://www.ncbi.nlm.nih.gov/pubmed/23427760", "http://www.ncbi.nlm.nih.gov/pubmed/21895933", "http://www.ncbi.nlm.nih.gov/pubmed/11002301", "http://www.ncbi.nlm.nih.gov/pubmed/22903482", "http://www.ncbi.nlm.nih.gov/pubmed/19238399", "http://www.ncbi.nlm.nih.gov/pubmed/19901837", "http://www.ncbi.nlm.nih.gov/pubmed/18499168", "http://www.ncbi.nlm.nih.gov/pubmed/14511039", "http://www.ncbi.nlm.nih.gov/pubmed/8813311" ], "ideal_answer": [ "Ultrasound" ], "exact_answer": [ "Ultrasound" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001743" ], "type": "factoid", "id": "5324bdba9b2d7acc7e00001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Modifications of the bladder wall (organ damage) in patients with bladder outlet obstruction: ultrasound parameters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427760", "endSection": "title" }, { "offsetInBeginSection": 434, "offsetInEndSection": 514, "text": "Early identification of bladder changes by noninvasive transabdominal ultrasound", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427760", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1182, "text": "Measurement of the bladder wall thickness (BWT) or detrusor wall thickness (DWT) by US is reliable,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427760", "endSection": "abstract" }, { "offsetInBeginSection": 1971, "offsetInEndSection": 2109, "text": "Also conventional US detects established signs of bladder damage: diverticulosis, trabecolations in the bladder wall (pseudo-diverticula),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427760", "endSection": "abstract" }, { "offsetInBeginSection": 2455, "offsetInEndSection": 2490, "text": "non-invasive US of the bladder wall", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427760", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 670, "text": "BladderScan BVM 9500 device (Diagnostic Ultrasound, Bothell, WA) was used to measure bladder wall thickness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22903482", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 92, "text": "ultrasonography-estimated bladder weight and bladder wall thickness ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21895933", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 97, "text": "To identify measurements of ultrasonography (US)-derived bladder wall thickness (BWT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21895933", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 287, "text": "transabdominal US measurements of BWT and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21895933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Transvaginal ultrasound measurement of bladder wall thickness: ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20438565", "endSection": "title" }, { "offsetInBeginSection": 70, "offsetInEndSection": 137, "text": "ultrasound (US) techniques to measure bladder wall thickness (BWT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20438565", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 196, "text": "Women underwent US measurement of BWT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20438565", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1395, "text": "Transabdominal and transperineal US for measuring BWT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20438565", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 182, "text": "ultrasound bladder and detrusor wall thickness", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20432327", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 107, "text": "Ultrasonic measurements of urinary bladders are suitable to quantify bladder wall hypertrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20432327", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1586, "text": "ultrasonic bladder wall measurements t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20432327", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 575, "text": "Preliminary data on the automatic measurement of bladder wall thickness were reported, suggesting a good repeatability and agreement with conventional ultrasound imaging", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901837", "endSection": "abstract" }, { "offsetInBeginSection": 50, "offsetInEndSection": 117, "text": " conventional ultrasound bladder wall thickness (BWT) measurements ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19238399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Ultrasonographic measurement of bladder wall thickness ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18499168", "endSection": "title" }, { "offsetInBeginSection": 378, "offsetInEndSection": 450, "text": "All children underwent ultrasonography to measure bladder wall thickness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18499168", "endSection": "abstract" }, { "offsetInBeginSection": 1721, "offsetInEndSection": 1805, "text": "Ultrasonographic assessment of bladder wall thickness is a sensitive screening tool ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18499168", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 281, "text": "ultrasound for bladder wall thickness (BWT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18335255", "endSection": "abstract" }, { "offsetInBeginSection": 45, "offsetInEndSection": 124, "text": "transabdominal ultrasonography for bladder volume and detrusor muscle thickness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17445666", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 595, "text": "Transabdominal ultrasonography with a high-frequency probe was performed to obtain the anterior, posterior, and lateral bladder wall thicknesses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17445666", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 905, "text": "ultrasonographic estimate of bladder wall thickness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14511039", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1263, "text": "ultrasonographic estimate of bladder wall thickness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14511039", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1440, "text": "there are marked differences in sonographic findings in male and female neonates in regard to renal pelvic dilatation, renal size and bladder wall thickness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11490298", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 297, "text": "BWT was measured by suprapubic ultrasonography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11002301", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 93, "text": "transvaginal ultrasound measurement of bladder wall thickness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8813311", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1030, "text": "The measurement of a mean bladder wall thickness greater than 5 mm with transvaginal ultrasound ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8813311", "endSection": "abstract" } ] }, { "body": "LY450139 is investigational name of which drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19692615", "http://www.ncbi.nlm.nih.gov/pubmed/20350302", "http://www.ncbi.nlm.nih.gov/pubmed/22710916", "http://www.ncbi.nlm.nih.gov/pubmed/22018341", "http://www.ncbi.nlm.nih.gov/pubmed/23278303", "http://www.ncbi.nlm.nih.gov/pubmed/19527190", "http://www.ncbi.nlm.nih.gov/pubmed/22778845", "http://www.ncbi.nlm.nih.gov/pubmed/20634579" ], "ideal_answer": [ "LY450139 is investigational name of Semagacestat. It is a \u03b3-secretase inhibitor developed for treatment for Alzheimer's disease. Chemical name of LY450139 is hydroxylvaleryl monobenzocaprolactam." ], "exact_answer": [ "semagacestat" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015507" ], "type": "factoid", "id": "54f35ad864850a5854000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The outcomes of the clinical trials of the \u03b3-secretase inhibitor Semagacestat (LY-450139) and the \u03b3-secretase modulator (GSM) Tarenflurbil were disappointing, but may not represent the end of the \u03b3-secretase era. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22710916", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 804, "text": "A selective BACE inhibitor and the \u03b3-secretase inhibitor LY450139 (semagacestat) were used to inhibit respective secretase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22018341", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 71, "text": "ACS chemical neuroscience molecule spotlight on semagacestat (LY450139).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22778845", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Semagacestat (LY450139) is a novel \u03b3-secretase inhibitor currently in late-stage development by Eli Lilly and Company as a potential treatment for Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22778845", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 358, "text": " The \u03b3-secretase inhibitor LY450139 (semagacestat) lowers plasma A\u03b2(1-40) and A\u03b2(1-42) in a dose-dependent manner but has no clear effect on the CSF level of these isoforms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20634579", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 176, "text": "TRODUCTION: LY450139 (semagacestat) inhibits gamma-secretase, a key enzyme for generation of amyloid beta (Abeta), the peptide deposited in plaques in Alzheimer disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20350302", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 801, "text": "Two potent gamma-secretase inhibitors (GSIs), DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester) and LY450139 (hydroxylvaleryl monobenzocaprolactam), were found to reduce the density of dendritic spines in wild-type mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19692615", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 121, "text": "velopment of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19527190", "endSection": "title" }, { "offsetInBeginSection": 269, "offsetInEndSection": 391, "text": "OBJECTIVE: This paper reviews the pharmacology and chemical efficacy of an A beta-lowering agent, semagacestat (LY450139).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19527190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "ACS chemical neuroscience molecule spotlight on semagacestat (LY450139).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22778845", "endSection": "title" }, { "offsetInBeginSection": 653, "offsetInEndSection": 777, "text": " A selective BACE inhibitor and the \u03b3-secretase inhibitor LY450139 (semagacestat) were used to inhibit respective secretase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22018341", "endSection": "abstract" } ] }, { "body": "Are there any Decision support systems for chronic pain management ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21249951", "http://www.ncbi.nlm.nih.gov/pubmed/20385018", "http://www.ncbi.nlm.nih.gov/pubmed/11524346", "http://www.ncbi.nlm.nih.gov/pubmed/23601912", "http://www.ncbi.nlm.nih.gov/pubmed/24073031" ], "ideal_answer": [ "Yes, there is a variety of decision support systems for chronic pain management.", "Clinical decision support systems are promising tools for improving behavioral medicine care for chronic pain.The use of a computer-based decision support system facilitates primary care physicians' management of chronic pain." ], "exact_answer": "yes", "type": "yesno", "id": "54fefbbc6ad7dcbc1200000a", "snippets": [ { "offsetInBeginSection": 422, "offsetInEndSection": 590, "text": "a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385018", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 709, "text": "We based the DSS on the existing ATHENA-DSS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385018", "endSection": "abstract" }, { "offsetInBeginSection": 1773, "offsetInEndSection": 1846, "text": "Use of this iterative process led to development of a multifunctional DSS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385018", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 927, "text": "interactive decision dashboard format", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23601912", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1144, "text": "We created a computerized, interactive clinical decision dashboard ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23601912", "endSection": "abstract" }, { "offsetInBeginSection": 2211, "offsetInEndSection": 2333, "text": "Interactive decision dashboards can be adapted for clinical use and have the potential to foster informed decision making.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23601912", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1190, "text": "Clinical decision support systems are promising tools for improving behavioral medicine care for chronic pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24073031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Improving Patient Safety Using ATHENA-Decision Support System Technology: ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249951", "endSection": "title" }, { "offsetInBeginSection": 237, "offsetInEndSection": 470, "text": "ATHENA-DSS is an automated decision support system developed in a collaboration between Stanford University and the U.S. Department of Veterans Affairs (VA) to increase guideline-adherent prescribing and to change physician behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The use of a computer-based decision support system facilitates primary care physicians' management of chronic pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11524346", "endSection": "title" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1459, "text": "The use of a CBDS system may improve the ability of PCPs to manage chronic pain and may also facilitate screening of consults to optimize specialist utilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11524346", "endSection": "abstract" } ] }, { "body": "Which gene has been found to be mutant in Lesch-Nyhan Disease patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8485579", "http://www.ncbi.nlm.nih.gov/pubmed/22132985", "http://www.ncbi.nlm.nih.gov/pubmed/22042773", "http://www.ncbi.nlm.nih.gov/pubmed/15571229", "http://www.ncbi.nlm.nih.gov/pubmed/23691025", "http://www.ncbi.nlm.nih.gov/pubmed/20159777", "http://www.ncbi.nlm.nih.gov/pubmed/15277709", "http://www.ncbi.nlm.nih.gov/pubmed/22157001", "http://www.ncbi.nlm.nih.gov/pubmed/1483694", "http://www.ncbi.nlm.nih.gov/pubmed/6853716", "http://www.ncbi.nlm.nih.gov/pubmed/8851475", "http://www.ncbi.nlm.nih.gov/pubmed/2875930", "http://www.ncbi.nlm.nih.gov/pubmed/23046577", "http://www.ncbi.nlm.nih.gov/pubmed/754871", "http://www.ncbi.nlm.nih.gov/pubmed/9799086", "http://www.ncbi.nlm.nih.gov/pubmed/20544510", "http://www.ncbi.nlm.nih.gov/pubmed/15140374", "http://www.ncbi.nlm.nih.gov/pubmed/7228031", "http://www.ncbi.nlm.nih.gov/pubmed/2671903", "http://www.ncbi.nlm.nih.gov/pubmed/3384338", "http://www.ncbi.nlm.nih.gov/pubmed/4624352", "http://www.ncbi.nlm.nih.gov/pubmed/24075303", "http://www.ncbi.nlm.nih.gov/pubmed/24001192", "http://www.ncbi.nlm.nih.gov/pubmed/7586656", "http://www.ncbi.nlm.nih.gov/pubmed/204459", "http://www.ncbi.nlm.nih.gov/pubmed/11336982" ], "ideal_answer": [ "Lesch-Nyhan Disease (LND) is the result of mutations in the X-linked gene encoding the purine metabolic enzyme, hypoxanthine guanine phosphoribosyl transferase (HPRT)." ], "exact_answer": [ "Hypoxanthine guanine phosphoribosyl transferase (HPRT) gene" ], "type": "factoid", "id": "5727ab040fd6f91b68000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "We describe a family of seven boys affected by Lesch-Nyhan disease with various phenotypes. Further investigations revealed a mutation c.203T>C in the gene encoding HGprt of all members, with substitution of leucine to proline at residue 68 (p.Leu68Pro)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Lesch-Nyhan disease (LND) is caused by deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24001192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Lesch-Nyhan Disease (LND) is the result of mutations in the X-linked gene encoding the purine metabolic enzyme, hypoxanthine guanine phosphoribosyl transferase (HPRT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23691025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Lesch-Nyhan disease and its attenuated variants are caused by mutations in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22157001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "The study of Lesch-Nyhan-diseased (LND) human brain is crucial for understanding how mutant hypoxanthine-phosphoribosyltransferase (HPRT) might lead to neuronal dysfunction. Since LND is a rare, inherited disorder caused by a deficiency of the enzyme HPRT, human neural stem cells (hNSCs) that carry this mutation are a precious source for delineating the consequences of HPRT deficiency and for developing new treatments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20159777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Molecular characterization and structure analysis of HPRT in a Chinese patient with Lesch-Nyhan disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24001192", "endSection": "title" }, { "offsetInBeginSection": 1118, "offsetInEndSection": 1341, "text": "An example is the isolation, by 6-thioguanine resistance, of cells deficient in hypoxanthine-guanine phosphoribosyl transferase -- the same deficiency that characterizes human patients with the X-linked Lesch-Nyhan disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/754871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Lesch-Nyhan disease (LND) is caused by deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24001192", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1055, "text": "In this research we demonstrate a model for Lesch-Nyhan disease by mutating the HPRT1 gene in human ES cells using homologous recombination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15277709", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 839, "text": "Lesch-Nyhan disease is caused by a mutation in the HPRT1 gene that triggers an overproduction of uric acid, causing gout-like symptoms and urinary stones, in addition to neurological disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15277709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Five independent mutations in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene were identified in a partially HPRT deficient patient with gout and in four Lesch-Nyhan patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1483694", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 386, "text": "Many different mutations throughout the HPRT coding region of Lesch-Nyhan patients have been described, including single base substitutions, partial or entire gene deletions, gene insertions or endoduplication of exons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8851475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "De novo purine biosynthesis has been studied in lymphocyte cell lines established from Lesch-Nyhan patients deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), in in vitro differentiating erythroleukaemic cell lines cloned from cells charactistic of virus-induced murine leukaemia, and in mutant hamster cells deficient in amidophosphoribosyltransferase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/204459", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1122, "text": "An example is the isolation, by 6-thioguanine resistance, of cells deficient in hypoxanthine-guanine phosphoribosyl transferase -- the same deficiency that characterizes human patients with the X-linked Lesch-Nyhan disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/754871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "HGPRT structural gene mutation in Lesch-Nyhan-syndrome as indicated by antigenic activity and reversion of the enzyme deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7228031", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Hypoxanthine-guanine phosphoribosyltransferase: characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4624352", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Mutation carrier testing in Lesch-Nyhan syndrome families: HPRT mutant frequency and mutation analysis with peripheral blood T lymphocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15140374", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Adenosine transport in HPRT deficient lymphocytes from Lesch-Nyhan disease patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15571229", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Molecular characterization of a deletion in the HPRT1 gene in a patient with Lesch-Nyhan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132985", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Molecular description of three macro-deletions and an Alu-Alu recombination-mediated duplication in the HPRT gene in four patients with Lesch-Nyhan disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336982", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Genetic basis of hypoxanthine guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome (HPRTFlint).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3384338", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Molecular characterization of two deletion events involving Alu-sequences, one novel base substitution and two tentative hotspot mutations in the hypoxanthine phosphoribosyltransferase (HPRT) gene in five patients with Lesch-Nyhan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9799086", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Southern analysis reveals a large deletion at the hypoxanthine phosphoribosyltransferase locus in a patient with Lesch-Nyhan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7586656", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "MicroRNA-mediated dysregulation of neural developmental genes in HPRT deficiency: clues for Lesch-Nyhan disease?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22042773", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6853716", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8485579", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Lesch-Nyhan syndrome is a rare X-linked recessive disorder of purine metabolism associated with a virtually complete deficiency of the enzyme hypoxanthine-guanine phosphoribosyl-transferase (HPRT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2671903", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1627, "text": "Normally spliced HPRT mRNA was quantified by real-time PCR in this patient, in control subjects, and in two Lesch Nyhan patient with splice mutations excluding exon 4 (patient B) and exon 8 (patient C) who had clinically a Lesch Nyhan disease phenotype. A minor amount of normally spliced HPRT mRNA was found in all the patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20544510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": " Lesch-Nyhan disease (LND) is caused by lack of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity. Mutations in HPRT1 gene show variability in type and location within the gene, and in certain patients the HPRT coding sequence is normal and the molecular defect cannot be found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046577", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1532, "text": "HPRT gene point mutations in three gouty arthritis and one Lesch-Nyhan patient have been identified by peptide sequencing. Six gross gene rearrangements have been identified in Lesch-Nyhan HPRT genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2875930", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 996, "text": "In two other mutants causing Lesch-Nyhan syndrome, a portion of the HPRT gene was deleted, and RNA splicing was missing in both mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1483694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Five independent mutations in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene were identified in a partially HPRT deficient patient with gout and in four Lesch-Nyhan patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1483694", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1551, "text": "Normally spliced HPRT mRNA was quantified by real-time PCR in this patient, in control subjects, and in two Lesch Nyhan patient with splice mutations excluding exon 4 (patient B) and exon 8 (patient C) who had clinically a Lesch Nyhan disease phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20544510", "endSection": "abstract" } ] }, { "body": "Which is the methyl donor of histone methyltransferases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2461933", "http://www.ncbi.nlm.nih.gov/pubmed/12819771", "http://www.ncbi.nlm.nih.gov/pubmed/22561085", "http://www.ncbi.nlm.nih.gov/pubmed/23086207", "http://www.ncbi.nlm.nih.gov/pubmed/20936105", "http://www.ncbi.nlm.nih.gov/pubmed/18693240", "http://www.ncbi.nlm.nih.gov/pubmed/17440941", "http://www.ncbi.nlm.nih.gov/pubmed/164278", "http://www.ncbi.nlm.nih.gov/pubmed/196592", "http://www.ncbi.nlm.nih.gov/pubmed/15292170", "http://www.ncbi.nlm.nih.gov/pubmed/10747987", "http://www.ncbi.nlm.nih.gov/pubmed/23236167", "http://www.ncbi.nlm.nih.gov/pubmed/17640894", "http://www.ncbi.nlm.nih.gov/pubmed/14633678", "http://www.ncbi.nlm.nih.gov/pubmed/6282265", "http://www.ncbi.nlm.nih.gov/pubmed/22624060", "http://www.ncbi.nlm.nih.gov/pubmed/18852888", "http://www.ncbi.nlm.nih.gov/pubmed/20303346", "http://www.ncbi.nlm.nih.gov/pubmed/18393372", "http://www.ncbi.nlm.nih.gov/pubmed/16086857", "http://www.ncbi.nlm.nih.gov/pubmed/21958314", "http://www.ncbi.nlm.nih.gov/pubmed/11309147", "http://www.ncbi.nlm.nih.gov/pubmed/8123667", "http://www.ncbi.nlm.nih.gov/pubmed/18790802", "http://www.ncbi.nlm.nih.gov/pubmed/21736313", "http://www.ncbi.nlm.nih.gov/pubmed/21782458", "http://www.ncbi.nlm.nih.gov/pubmed/21779408" ], "triples": [ { "p": "http://purl.uniprot.org/core/ecName", "s": "http://linkedlifedata.com/resource/#_413252395935006", "o": "2.1.1.-" } ], "ideal_answer": [ "The major methyl donor of histone methyltransferases (HMTs) is S-adenosyl-L\u2013methionine (SAM, AdoMet)." ], "exact_answer": [ "S-adenosyl-L\u2013methionine", "SAM", "AdoMet", "S-Adenosylmethionine", "adenosylmethionine", "S-Adenosyl methionine" ], "concepts": [ "http://www.uniprot.org/uniprot/DOT1_CANGA", "http://www.uniprot.org/uniprot/CLR4_SCHPO", "http://www.uniprot.org/uniprot/DOT1_ASPFU", "http://www.uniprot.org/uniprot/DOT1_CRYNJ", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031060", "http://www.uniprot.org/uniprot/SET1_DICDI", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031062", "http://www.uniprot.org/uniprot/DOT1_NEUCR", "http://www.uniprot.org/uniprot/DOT1_CRYNB", "http://www.uniprot.org/uniprot/DOT1_KLULA", "http://www.uniprot.org/uniprot/SUV39_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008469", "http://www.uniprot.org/uniprot/DOT1_USTMA", "http://www.uniprot.org/uniprot/DOT1_ASPOR", "http://www.uniprot.org/uniprot/SUV39_DROPS", "http://www.uniprot.org/uniprot/DOT1L_DICDI", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016571", "http://www.uniprot.org/uniprot/DOT1_CANAL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042054" ], "type": "factoid", "id": "516e7fda298dcd4e51000081", "snippets": [ { "offsetInBeginSection": 424, "offsetInEndSection": 584, "text": "While SAMe is a methyl donor, MTA is an inhibitor of methylation. SAMe can convert to MTA spontaneously, so the effect of exogenous SAMe may be mediated by MTA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18393372", "endSection": "sections.0" }, { "offsetInBeginSection": 727, "offsetInEndSection": 985, "text": "Based on known SET domain structures, the mutations likely affect either the lysine-substrate binding pocket, the binding site for the adenosylmethionine methyl donor, or a critical tyrosine predicted to interact with the substrate lysine epsilon-amino group", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18693240", "endSection": "sections.0" }, { "offsetInBeginSection": 598, "offsetInEndSection": 713, "text": "Also, S-adenosylhomocysteine or methyl donor deficiency inhibits RIZ1 and other H3 lysine 9 methylation activities.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14633678", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Angiosperms synthesize S-methylmethionine (SMM) from methionine (Met) and S-adenosylmethionine (AdoMet) in a unique reaction catalyzed by Met S-methyltransferase (MMT). SMM serves as methyl donor for Met synthesis from homocysteine, catalyzed by homocysteine S-methyltransferase (HMT).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11309147", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Plants synthesize S-methylmethionine (SMM) from S-adenosylmethionine (AdoMet), and methionine (Met) by a unique reaction and, like other organisms, use SMM as a methyl donor for Met synthesis from homocysteine (Hcy).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10747987", "endSection": "sections.0" }, { "offsetInBeginSection": 813, "offsetInEndSection": 925, "text": "AtHMT-1 and -2 both utilize l-SMM or (S,S)-AdoMet as a methyl donor in vitro and have higher affinities for SMM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10747987", "endSection": "sections.0" }, { "offsetInBeginSection": 481, "offsetInEndSection": 715, "text": "When the serine residue is mutated to glutamic acid, which mimics the phosphorylated serine residue, the mutant CARM1 exhibits diminished ability to bind the methyl donor adenosylmethionine and diminished histone methylation activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17640894", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "S-adenosylmethionine (SAMe), the major methyl donor for DNA and histone methylation was fed with ethanol for 1month in order to modify the effects of ethanol on rat liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20303346", "endSection": "sections.0" }, { "offsetInBeginSection": 391, "offsetInEndSection": 684, "text": "To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23236167", "endSection": "sections.0" }, { "offsetInBeginSection": 397, "offsetInEndSection": 557, "text": "The enzyme was capable of transferring methyl groups to selected lysine residues in a substrate protein using S-adenosyl-l-methionine (SAM) as the methyl donor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086207", "endSection": "sections.0" }, { "offsetInBeginSection": 289, "offsetInEndSection": 423, "text": "SAM is the main methyl group donor for methyltransferases to modify DNA, RNA, protein, metabolites, or phospholipid target substrates.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561085", "endSection": "sections.0" }, { "offsetInBeginSection": 232, "offsetInEndSection": 539, "text": "To control the enzymatic activity of vSET in vivo with an engineered S-adenosyl-l-methionine (SAM) analogue as methyl donor cofactor, we have carried out structure-guided design, synthesis, and characterization of orthogonal vSET methyltransferase mutant/SAM analogue pairs using a \"bump-and-hole\" strategy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21958314", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Protein lysine methyltransferases are important regulators of epigenetic signaling.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21782458", "endSection": "sections.0" }, { "offsetInBeginSection": 124, "offsetInEndSection": 265, "text": "One of the well-studied PTMs, arginine methylation, is catalyzed by protein arginine methyltransferases (PRMTs) with SAM as the methyl donor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21736313", "endSection": "sections.0" }, { "offsetInBeginSection": 424, "offsetInEndSection": 489, "text": "While SAMe is a methyl donor, MTA is an inhibitor of methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18393372", "endSection": "sections.0" }, { "offsetInBeginSection": 184, "offsetInEndSection": 337, "text": "The purified cytochrome can act as a methyl acceptor for a methyltransferase activity in the cell extract that uses S-adenosylmethionine as methyl donor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6282265", "endSection": "sections.0" }, { "offsetInBeginSection": 194, "offsetInEndSection": 259, "text": "This enzyme utilizes S-adenosyl-L-methionine as the methyl donor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/196592", "endSection": "sections.0" } ] }, { "body": "How are human accelerated regions (HAR) defined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20179156", "http://www.ncbi.nlm.nih.gov/pubmed/22412940", "http://www.ncbi.nlm.nih.gov/pubmed/20502635", "http://www.ncbi.nlm.nih.gov/pubmed/16915236", "http://www.ncbi.nlm.nih.gov/pubmed/22075116" ], "ideal_answer": [ "Human accelerated regions (HAR) are defined as previously slowly evolving regions of the genome that have evolved most quickly along the human lineage. These represent genomic regions that are conserved among vertebrates but have accumulated substitutions on the human lineage at an accelerated rate." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012045" ], "type": "summary", "id": "51603912298dcd4e5100003b", "snippets": [ { "offsetInBeginSection": 344, "offsetInEndSection": 419, "text": "regions in the human genome that show significant evolutionary acceleration", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16915236", "endSection": "sections.0" }, { "offsetInBeginSection": 432, "offsetInEndSection": 576, "text": "This identified Human Accelerated Region 1 (HAR1), a rapidly-evolving cis-antisense locus that is specifically transcribed in the nervous system", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20179156", "endSection": "sections.0" }, { "offsetInBeginSection": 320, "offsetInEndSection": 419, "text": "We devised a ranking of regions in the human genome that show significant evolutionary acceleration", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16915236", "endSection": "sections.0" } ] }, { "body": "Carbapenemase-producing gram-negative bacteria is a major health concern because their resistance to antibiotics.\nList the most frequent carbapenemases found in Enterobacteriaceae.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19386850", "http://www.ncbi.nlm.nih.gov/pubmed/20534805", "http://www.ncbi.nlm.nih.gov/pubmed/22553235", "http://www.ncbi.nlm.nih.gov/pubmed/20686438", "http://www.ncbi.nlm.nih.gov/pubmed/22796889", "http://www.ncbi.nlm.nih.gov/pubmed/20960935", "http://www.ncbi.nlm.nih.gov/pubmed/20237104", "http://www.ncbi.nlm.nih.gov/pubmed/17594211", "http://www.ncbi.nlm.nih.gov/pubmed/18070960", "http://www.ncbi.nlm.nih.gov/pubmed/17227206", "http://www.ncbi.nlm.nih.gov/pubmed/22383444", "http://www.ncbi.nlm.nih.gov/pubmed/20649801", "http://www.ncbi.nlm.nih.gov/pubmed/20542902", "http://www.ncbi.nlm.nih.gov/pubmed/23114438" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/mesh/Enterobacteriaceae", "o": "Enterobacteriaceae" } ], "ideal_answer": [ "The most frequent carbapenemases in Enterobacteriaceae are OXA-48, KPC, VIM, NDM, IMP, SME, NMC, GES, IMI and MBL." ], "exact_answer": [ [ "OXA-48" ], [ "KPC" ], [ "VIM" ], [ "NDM" ], [ "IMP" ], [ "SME" ], [ "NMC" ], [ "GES" ], [ "IMI" ], [ "MBL" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004352", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000903", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046677", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004756", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004755", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024881", "http://www.uniprot.org/uniprot/BLAN_ENTCL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015780" ], "type": "list", "id": "515870cdd24251bc0500008f", "snippets": [ { "offsetInBeginSection": 513, "offsetInEndSection": 653, "text": "The most frequent carbapenemases in Enterobacteriaceae were OXA-48, KPC and VIM-1; in P. aeruginosa it was VIM-2 and in A. baumannii OXA-23.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23114438", "endSection": "sections.0" }, { "offsetInBeginSection": 485, "offsetInEndSection": 576, "text": "bla(IMP), bla(VIM), bla(SPM), bla(SIM) and bla(GIM), and of bla(KPC), bla(NDM) and bla(OXA-", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22796889", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Detection of NDM-1, VIM-1, KPC, OXA-48, and OXA-162 carbapenemases by matrix-assisted laser desorption ionization-time of flight mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553235", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The Check-MDR CT102 DNA microarray enables detection of the most prevalent carbapenemases (NDM, VIM, KPC, OXA-48 and IMP)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383444", "endSection": "sections.0" }, { "offsetInBeginSection": 642, "offsetInEndSection": 706, "text": "63 KPC producers, 47 MBL producers, and 31 KPC and MBL producers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20542902", "endSection": "sections.0" }, { "offsetInBeginSection": 347, "offsetInEndSection": 475, "text": "OXA-48 producers were poorly detected, but all systems reliably detected isolates with KPC and most with metallo-carbapenemases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20534805", "endSection": "sections.0" }, { "offsetInBeginSection": 347, "offsetInEndSection": 699, "text": "Producers of IMP-, VIM-, and KPC-type carbapenemases with high levels of resistance to cephalosporins and to carbapenems were detected at 1x10(1) CFU/ml. The OXA-48 producers were not detected on ChromID ESBL medium unless coexpressing ESBLs, whereas carbapenemase-producing isolates with MICs of <4 microg/ml were not detected on CHROMagar KPC medium.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20237104", "endSection": "sections.0" }, { "offsetInBeginSection": 288, "offsetInEndSection": 641, "text": "The most frequent carbapenemase was KPC-2 or -3 (73 strains), followed by VIM-1 (14), IMP-1 (11), SME-2 (5), and NMC-A (1). All serine carbapenemases were detected in the United States, while MbetaL-producing strains were isolated in Europe. Carbapenemase-producing Enterobacteriaceae showed high rates of resistance to most antimicrobial agents tested.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18070960", "endSection": "sections.0" }, { "offsetInBeginSection": 1672, "offsetInEndSection": 1848, "text": "By using this methodology, isolates producing KPC, GES, Sme, IMI, and NMC-A carbapenemases were successfully distinguished from those producing other classes of beta-lactamases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19386850", "endSection": "sections.0" }, { "offsetInBeginSection": 887, "offsetInEndSection": 975, "text": "KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) i", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17227206", "endSection": "sections.0" }, { "offsetInBeginSection": 167, "offsetInEndSection": 243, "text": "K. pneumoniae strains with known KPC (n\u2003=\u200331) or VIM (n\u2003=\u200320) carbapenemases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20649801", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Carbapenemases including Klebsiella pneumoniae carbapenemases (KPC) are widespread among clinical isolates in the family Enterobacteriaceae.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20960935", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Outbreak of vim-1-carbapenemase-producing Enterobacter cloacae in a pediatric intensive care unit.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20686438", "endSection": "title" }, { "offsetInBeginSection": 340, "offsetInEndSection": 498, "text": "mergence of pediatric infections caused by carbapenemases-producing Enterobacteriaceae is a critical issue as they are resistant to most \u03b2-lactam antibiotics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20686438", "endSection": "sections.0" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1531, "text": "SME-2-producing S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC-A was found in one E. cloacae strain from New York. In contrast, metallo-beta-lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates) were detected in Turkey, while VIM-1-producing strains were found in Italy (Enterobacter spp.) and Greece (Klebsiella pneumoniae).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17227206", "endSection": "sections.0" }, { "offsetInBeginSection": 402, "offsetInEndSection": 553, "text": "d several simple confirmatory methods that allow the recognition of bacteria producing class A carbapenemases, including KPC, Sme, IMI, NMC-A, and GES,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19386850", "endSection": "sections.0" } ] }, { "body": "How are GRBs (Genomic Regulatory Blocks) defined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19561171", "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "http://www.ncbi.nlm.nih.gov/pubmed/20080751", "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "http://www.ncbi.nlm.nih.gov/pubmed/18047696", "http://www.ncbi.nlm.nih.gov/pubmed/22666536", "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "http://www.ncbi.nlm.nih.gov/pubmed/22722344", "http://www.ncbi.nlm.nih.gov/pubmed/23193254", "http://www.ncbi.nlm.nih.gov/pubmed/19698106", "http://www.ncbi.nlm.nih.gov/pubmed/22234889", "http://www.ncbi.nlm.nih.gov/pubmed/19969543" ], "ideal_answer": [ "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene.", "Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, often immobilizing other, unrelated genes into long-lasting syntenic arrangements. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. Although gene order in hox and other gene clusters has long been known to be conserved because of shared regulatory sequences or overlapping transcriptional units, the chromosomal areas found through insertional hotspots contain only one or a few developmental regulatory genes as well as phylogenetically unrelated genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development.", "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. " ], "type": "summary", "id": "56eaf4e6107309bc2f000001", "snippets": [ { "offsetInBeginSection": 546, "offsetInEndSection": 986, "text": "Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 380, "text": "We present evidence that microsynteny has been retained to keep large arrays of highly conserved noncoding elements (HCNEs) intact. These arrays span key developmental regulatory genes, forming genomic regulatory blocks (GRBs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 537, "text": "We recently described GRBs in vertebrates, where most HCNEs function as enhancers and HCNE arrays specify complex expression programs of their target genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1336, "text": "Although gene order in hox and other gene clusters has long been known to be conserved because of shared regulatory sequences or overlapping transcriptional units, the chromosomal areas found through insertional hotspots contain only one or a few developmental regulatory genes as well as phylogenetically unrelated genes. We have termed these regions genomic regulatory blocks (GRBs), and show that they underlie the phenomenon of conserved synteny through all sequenced vertebrate genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18047696", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 200, "text": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 309, "text": "The target genes are most often transcription factors involved in embryonic development and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 493, "text": "GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1302, "text": "We show evidence that GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1705, "text": "GRB targets are genes with a number of unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, often immobilizing other, unrelated genes into long-lasting syntenic arrangements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19698106", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 830, "text": "Specifically, we discuss the recently discovered genomic regulatory blocks which we argue are principal units of vertebrate genome evolution and serve as the foundations onto which evolutionary innovations are built through sequence evolution and insertion of new cis-regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561171", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 519, "text": "We show that these LD blocks contain highly conserved noncoding elements and overlap with the genomic regulatory blocks of the transcription factor genes HHEX, SOX4, and IRX3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Using a comparative genomics approach to reconstruct the fate of genomic regulatory blocks (GRBs) and identify exonic remnants that have survived the disappearance of their host genes after whole-genome duplication (WGD) in teleosts, we discover a set of 38 candidate cis-regulatory coding exons (RCEs) with predicted target genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19969543", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 558, "text": "They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 1028, "text": " In this paper, we therefore systematically investigate the regulatory landscape around conserved self-transcribed miRNAs (ST miRNAs), with their own known or computationally inferred promoters, by analyzing the hallmarks of GRB target genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "endSection": "abstract" }, { "offsetInBeginSection": 1656, "offsetInEndSection": 1935, "text": "Based on these results we used both an elevated HCNE density in the genomic vicinity as well as the presence of a bivalent promoter to identify 29 putative GRB target miRNAs/miRNA clusters, over two-thirds of which are known to play a role during development and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "endSection": "abstract" }, { "offsetInBeginSection": 1936, "offsetInEndSection": 2063, "text": "Furthermore these predictions include miRNAs of the miR-9 family, which are the only experimentally verified GRB target miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "endSection": "abstract" }, { "offsetInBeginSection": 2076, "offsetInEndSection": 2264, "text": "A subset of the conserved miRNA loci we investigated exhibits typical characteristics of GRB target genes, which may partially explain their complex expression profiles during development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Developmental genes are regulated by complex, distantly located cis-regulatory modules (CRMs), often forming genomic regulatory blocks (GRBs) that are conserved among vertebrates and among insects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234889", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 281, "text": "We have investigated GRBs associated with Iroquois homeobox genes in 39 metazoans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234889", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 982, "text": "Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722344", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 532, "text": "As most of them occur as clusters near potential target genes, the database is organized along two hierarchical levels: individual UCNEs and ultra-conserved genomic regulatory blocks (UGRBs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193254", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 840, "text": "Detailed synteny maps between the human and other genomes are provided for all UGRBs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1378, "text": "Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722344", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1498, "text": "We have termed these regions genomic regulatory blocks (GRBs), and show that they underlie the phenomenon of conserved synteny through all sequenced vertebrate genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18047696", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 846, "text": "They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 540, "text": "These elements are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 679, "text": "The Sonic Hedgehog (Shh) genomic regulatory block (GRB) is one of the best functionally characterized examples, with several discrete enhancers reported within its introns, vast upstream gene-free region and neighboring genes (Lmbr1 and Rnf32).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22666536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "BACKGROUND: Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374772", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 436, "text": "These elements are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Developmental genes are regulated by complex, distantly located cis-regulatory modules (CRMs), often forming genomic regulatory blocks (GRBs) that are conserved among vertebrates and among insects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234889", "endSection": "abstract" } ] }, { "body": "What is the gene frequently mutated in Multiple endocrine neoplasia 2 (MEN2) and Hisrchsprung disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18062802", "http://www.ncbi.nlm.nih.gov/pubmed/17525482", "http://www.ncbi.nlm.nih.gov/pubmed/23210566", "http://www.ncbi.nlm.nih.gov/pubmed/21542403", "http://www.ncbi.nlm.nih.gov/pubmed/9745455", "http://www.ncbi.nlm.nih.gov/pubmed/16712668", "http://www.ncbi.nlm.nih.gov/pubmed/19826964", "http://www.ncbi.nlm.nih.gov/pubmed/19177457", "http://www.ncbi.nlm.nih.gov/pubmed/15991157", "http://www.ncbi.nlm.nih.gov/pubmed/21678021", "http://www.ncbi.nlm.nih.gov/pubmed/7641404", "http://www.ncbi.nlm.nih.gov/pubmed/21422799", "http://www.ncbi.nlm.nih.gov/pubmed/22199277", "http://www.ncbi.nlm.nih.gov/pubmed/20152359" ], "ideal_answer": [ "The Ret gene may have gain of mutation functions in MEN2 cancer as well as loss of function mutations in Hirschprung disease." ], "exact_answer": [ "Ret" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018813", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627" ], "type": "factoid", "id": "5171438a8ed59a060a000007", "snippets": [ { "offsetInBeginSection": 2064, "offsetInEndSection": 2196, "text": "Our results further substantiate that gene scanning of all relevant RET exons is a powerful tool in the management of MEN2 patients,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23210566", "endSection": "sections.0" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1274, "text": "We identified RET mutations in seven of 13 MTCs: five RET-positive cases revealed a mutation in exon 16 (M918T) and two a mutation in exon 10 (C618S and C620S). In four of the RET-positive cases, the mutation was inherited, out of which three were reportedly associated with a multiple endocrine neoplasia type 2 (MEN2) syndrome, i.e. MEN2A (C618S), MEN2A/familial MTC (FMTC) (C620S), and MEN2B (M918T).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22199277", "endSection": "sections.0" }, { "offsetInBeginSection": 2243, "offsetInEndSection": 2328, "text": "RET gene mutation carries a risk of MEN2 and MTC in all ethnic groups in South Africa", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542403", "endSection": "sections.0" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1361, "text": "Mutational screening of the RET gene identified a common mutation (C618R) in all 8 (7 FMTC and 1 MEN2A)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21422799", "endSection": "sections.0" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1330, "text": "Gene mutation in the RET-620 position carries significant risk and may be part of a targeted investigation of high-risk areas in HSCR", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20152359", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 730, "text": "Activating germline RET mutations are presented in patients with familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia (MEN) types 2A and 2B, whereas inactivating germline mutations in patients with Hirschsprung's disease (HSCR). The aim of this study was to evaluate genotype-phenotype correlations of the frequently discussed Tyr791Phe mutation in exon 13 of the RET proto-oncogene. Screening of three groups of patients was performed (276 families with medullary thyroid carcinoma (MTC), 122 families with HSCR, and 29 patients with pheochromocytoma). We found this mutation in 3 families with apparently sporadic MTC, 3 families with FMTC/MEN2, 1 patient with pheochromocytoma, and 3 families with HSCR.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19826964", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Multiple endocrine neoplasia type 2 (MEN2) is an inherited, autosomal-dominant disorder caused by deleterious mutations within the RET protooncogene. MEN2 RET mutations are mainly heterozygous, missense sequence changes found in RET exons 10, 11, and 13-16", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19177457", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 316, "text": "Medullary thyroid carcinoma (MTC) occurs both sporadically and in the context of autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC), which are caused by activating germline mutations in the RET proto-oncogene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16712668", "endSection": "sections.0" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1261, "text": "The germline mutation was detected because of the systematic genetic screening of the RET proto-oncogene, which is useful for genetic counseling of potential risk of HSCR and MTC in other family members. This family could be added to the small worldwide cohort of families with MEN2A/FMTC-HSCR.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15991157", "endSection": "sections.0" }, { "offsetInBeginSection": 123, "offsetInEndSection": 462, "text": "Germline mutations of the ret protooncogene are the underlying cause of the MEN2 syndromes and a proportion of cases of HSCR. In this report, we describe a new kindred in which the MEN2 and HSCR phenotypes are associated with a single C620S point mutation at one of the cysteine codons of the extracellular domain of the ret protooncogene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9745455", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 376, "text": "Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between true sporadic MTC and a new mutation familial case is important for future clinical management of both the patient and family. The susceptibility gene for MEN 2 is the RET proto-oncogene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7641404", "endSection": "sections.0" } ] }, { "body": "Which are the clinical characteristics of isolated Non-compaction cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20860157", "http://www.ncbi.nlm.nih.gov/pubmed/22801312", "http://www.ncbi.nlm.nih.gov/pubmed/21193437", "http://www.ncbi.nlm.nih.gov/pubmed/17047599", "http://www.ncbi.nlm.nih.gov/pubmed/19664240", "http://www.ncbi.nlm.nih.gov/pubmed/21246178", "http://www.ncbi.nlm.nih.gov/pubmed/17174235", "http://www.ncbi.nlm.nih.gov/pubmed/16170691", "http://www.ncbi.nlm.nih.gov/pubmed/22051823", "http://www.ncbi.nlm.nih.gov/pubmed/17947214", "http://www.ncbi.nlm.nih.gov/pubmed/18700964", "http://www.ncbi.nlm.nih.gov/pubmed/19417170", "http://www.ncbi.nlm.nih.gov/pubmed/22574099", "http://www.ncbi.nlm.nih.gov/pubmed/20386670", "http://www.ncbi.nlm.nih.gov/pubmed/24367719", "http://www.ncbi.nlm.nih.gov/pubmed/20333604", "http://www.ncbi.nlm.nih.gov/pubmed/12668828", "http://www.ncbi.nlm.nih.gov/pubmed/15618076" ], "ideal_answer": [ "The clinical characteristics of isolated Non-compaction cardiomyopathy are excessively thickened endocardial layer with deep intertrabecular recesses (with ratio of non-compacted to compacted myocardium >2), heart failure, syncope, ventricular arrhythmias, stroke, pulmonary hypertension, complete left branch conductive block, sick sinus syndrome and paroxysmal supraventricular tachycardia" ], "exact_answer": [ [ "excessively thickened endocardial layer with deep intertrabecular recesses" ], [ "ratio of non-compacted to compacted myocardium >2" ], [ "heart failure" ], [ "syncope" ], [ "ventricular arrhythmias" ], [ "stroke" ], [ "Pulmonary hypertension" ], [ "complete left branch conductive block" ], [ "sick sinus syndrome" ], [ "paroxysmal supraventricular tachycardia" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056830" ], "type": "list", "id": "52f4f1d62059c6d71c00001c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 223, "text": "Non compaction cardiomyopathy is a rare disorder caused by the arrest of myocardial compaction during embryogenesis, leading to a non compacted endocardial layer with marked hypertrabeculation and deep recesses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051823", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 899, "text": "The form of presentation was heart failure in 53% of subjects, syncope in 20%o, ventricular arrhythmias in 13%o and stroke in 7%>. Left ventricular end-diastolic diameter was 66 \u00b1 11 mm and estimated ejection fraction was 27 \u00b1 10%>. Apical and/or mid-ventricular segments of the left ventricle were involved in all the cases. Pulmonary hypertension was present in 40%o.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22051823", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1818, "text": "Prominent hypertrabecularisation (ratio of non-compacted to compacted myocardium >2) in the apical and mid left ventricular segments is typical for non-compaction cardiomyopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21246178", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 403, "text": "Isolated ventricular non-compaction or non-compaction cardiomyopathy (NCCM) is characterized by an excessively thickened endocardial layer with deep intertrabecular recesses, reminiscent of the myocardium during early embryogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17947214", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 1024, "text": "Sudden cardiac death (including 1 occurred while following-up) was reported in 7 family members (17.5%, 7/40). LVNC was diagnosed in 10 out of the 33 family members (30.3%) and heart enlargement was evidenced in 3, heart failure in 2, complete left branch conductive block in 3, serious sick sinus syndrome (SSS) treated with permanent pacemaker implantation in 1 and paroxysmal supraventricular tachycardia treated with radiofrequency ablation procedure in 1 out of these 10 LVNC patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801312", "endSection": "abstract" } ] }, { "body": "What is STARR-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "http://www.ncbi.nlm.nih.gov/pubmed/24685159" ], "ideal_answer": [ "STARR-seq is a method to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans." ], "type": "summary", "id": "56b8ccc5156496395c000003", "snippets": [ { "offsetInBeginSection": 157, "offsetInEndSection": 892, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Genome-wide quantitative enhancer activity maps identified by STARR-seq.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "title" }, { "offsetInBeginSection": 888, "offsetInEndSection": 991, "text": "STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 739, "text": "We used STARR-seq, a recently developed enhancer-screening assay, and ecdysone signaling in two different Drosophila cell types to derive genome-wide hormone-dependent enhancer-activity maps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685159", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 550, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 883, "text": "When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 355, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 551, "text": "We used STARR-seq, a recently developed enhancer-screening assay, and ecdysone signaling in two different Drosophila cell types to derive genome-wide hormone-dependent enhancer-activity maps. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685159", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 789, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 892, "text": "STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 354, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 620, "text": "When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 621, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 893, "text": "STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 551, "text": "We used STARR-seq, a recently developed enhancer-screening assay, and ecdysone signaling in two different Drosophila cell types to derive genome-wide hormone-dependent enhancer-activity maps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685159", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 355, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract" } ] }, { "body": "In which genomic positions is the histone variant macroH2A enriched?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16738309", "http://www.ncbi.nlm.nih.gov/pubmed/16213499", "http://www.ncbi.nlm.nih.gov/pubmed/20670405", "http://www.ncbi.nlm.nih.gov/pubmed/14608463", "http://www.ncbi.nlm.nih.gov/pubmed/20937776", "http://www.ncbi.nlm.nih.gov/pubmed/12082075", "http://www.ncbi.nlm.nih.gov/pubmed/17570398", "http://www.ncbi.nlm.nih.gov/pubmed/18195046", "http://www.ncbi.nlm.nih.gov/pubmed/18936163" ], "ideal_answer": [ "macroH2A1 is enriched on the inactive X chromosome in female mammalian cells, where it functions to maintain gene silencing. The transcribed regions of most active genes are depleted of macroH2A, often in sharply localized domains that show depletion of 4-fold or more relative to bulk mouse liver chromatin. This repressor activity of marcroH2A is further supported by the substantial and relatively uniform macroH2A1 enrichment along the inactive X chromosome, which averages 4-fold. In addition to localizing to the MCB, macroH2A accumulates at a perinuclear structure centered at the centrosome" ], "exact_answer": [ [ "Repressed regions" ], [ "Inactive X chromosome" ], [ "Centromeres" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.biosemantics.org/jochem#4278518", "http://www.uniprot.org/uniprot/H2AW_MOUSE" ], "type": "list", "id": "533c384dc45e133714000006", "snippets": [ { "offsetInBeginSection": 291, "offsetInEndSection": 429, "text": "Although macroH2A1 nucleosomes are widely distributed across the genome, their local concentration varies over a range of 100-fold or more", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937776", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 614, "text": "The transcribed regions of most active genes are depleted of macroH2A1, often in sharply localized domains that show depletion of 4-fold or more relative to bulk mouse liver chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937776", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1119, "text": "This repressor activity is further supported by the substantial and relatively uniform macroH2A1 enrichment along the inactive X chromosome, which averages 4-fold", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937776", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1315, "text": "mH2A1 consistently colocalizes with a heterochromatin marker (H3K27me2; histone H3 trimethylated at lysine 27) and mH2A2 with a euchromatin marker (H3K4me3; histone H3 trimethylated at lysine 4)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670405", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1408, "text": "Similar results were found for the L41gene, with enrichment of mH2A in the promoter region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670405", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 358, "text": "By using highly specific antibodies against mH2A1 and stable HEK 293 cell lines expressing either green fluorescent protein (GFP)-mH2A1 or GFP-H2A, we found that the Xi chromosome contains approximately 1.5-fold more mH2A1 than the autosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18936163", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 775, "text": "The data show that mH2A1 is uniformly distributed across the entire Xi chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18936163", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 892, "text": "Interestingly, a stronger mH2A1 enrichment along the pseudoautosomal X chromosome region was observed in both sexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18936163", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 596, "text": "macroH2A1 nucleosomes were enriched on endogenous MLVs, with the highest enrichment occurring on the 5' end of pro-pol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18195046", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 564, "text": "macroH2A1 is enriched on the inactive X chromosome in female mammalian cells, where it functions to maintain gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17570398", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 269, "text": "We found that macroH2A1 was depleted on the transcribed regions of active genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738309", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 528, "text": "In contrast, macroH2A1 was concentrated on the inactive X chromosome, consistent with our previous immunofluorescence studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738309", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 812, "text": "These results support the hypothesis that macroH2As function as transcriptional repressors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738309", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 1198, "text": "Taking into account the properties of macroH2A toward chromatin structure and dynamics and its role in gene repression our data suggest that the increased expression of macroH2A and the hypermethylation of DNA which occurs upon winter-acclimatization plays a major role for the reorganization of chromatin structure and the regulation of gene expression during the physiological adaptation to a colder environment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16213499", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 380, "text": "Inactivation is a multistep process that involves a large non-coding RNA termed XIST, a variety of epigenetic modifications of chromatin, and alterations in protein composition such as enrichment of the histone variant macroH2A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14608463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "One of several features acquired by chromatin of the inactive X chromosome (Xi) is enrichment for the core histone H2A variant macroH2A within a distinct nuclear structure referred to as a macrochromatin body (MCB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12082075", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 328, "text": "In addition to localizing to the MCB, macroH2A accumulates at a perinuclear structure centered at the centrosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12082075", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1110, "text": "The centrosomal pool of macroH2A1 accumulates in the presence of an inhibitor of the 20S proteasome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12082075", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 849, "text": "Although the MCB dissipates during late S phase and G2 before reforming in late G1, macroH2A1 remains associated during mitosis with specific regions of the Xi, including at the X inactivation center", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12082075", "endSection": "abstract" } ] }, { "body": "Does amiodarone affect thyroid hormone receptors in the myocardium?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17535870", "http://www.ncbi.nlm.nih.gov/pubmed/9781936", "http://www.ncbi.nlm.nih.gov/pubmed/10445678", "http://www.ncbi.nlm.nih.gov/pubmed/7598731" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000638", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.biosemantics.org/jochem#4274241", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "yesno", "id": "516d5baa298dcd4e51000078", "snippets": [ { "offsetInBeginSection": 732, "offsetInEndSection": 845, "text": "AM and Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870", "endSection": "sections.0" }, { "offsetInBeginSection": 847, "offsetInEndSection": 933, "text": "In the LVW, AM and Dron decreased TRbeta 1 and, interestingly, AM increased TRalpha 1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870", "endSection": "sections.0" }, { "offsetInBeginSection": 935, "offsetInEndSection": 975, "text": "n the apex, AM also increased TRalpha 2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870", "endSection": "sections.0" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1324, "text": "Both in treated and untreated mice, TRalpha2 mRNA had the highest density in mouse heart, whereas TRbeta2 mRNA had the lowest density. Amiodarone dose-dependently downregulated the levels of TRalpha1 and beta1 mRNA in comparison to the control.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445678", "endSection": "sections.0" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1648, "text": "amiodarone subtype selectively downregulates the TR mRNA levels in mouse myocardium in a dose-dependent manner.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10445678", "endSection": "sections.0" }, { "offsetInBeginSection": 1613, "offsetInEndSection": 1691, "text": "Western blot analysis revealed no change in the expression of the ThR protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9781936", "endSection": "sections.0" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1094, "text": "Amiodarone and T3, respectively, downregulated T3R alpha 1, T3R beta 1, T3R beta 2 (p < 0.05), but did not affect the levels of T3R alpha 2. Amiodarone and T3, added together, upregulated T3R alpha 2 and T3R beta 1 (p < 0.05) as compared to amiodarone or T3 alone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7598731", "endSection": "sections.0" } ] }, { "body": "From which sequence does the Alu repeat originate from?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9694666", "http://www.ncbi.nlm.nih.gov/pubmed/8576966", "http://www.ncbi.nlm.nih.gov/pubmed/16343813", "http://www.ncbi.nlm.nih.gov/pubmed/12815945", "http://www.ncbi.nlm.nih.gov/pubmed/12167372", "http://www.ncbi.nlm.nih.gov/pubmed/9395063" ], "ideal_answer": [ "The presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric element, The origin of Alu subfamilies in human populations may be related to evolution of chromosome Y." ], "exact_answer": [ "7SL RNA" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020087" ], "type": "factoid", "id": "56ffd08bcf1c325851000009", "snippets": [ { "offsetInBeginSection": 164, "offsetInEndSection": 298, "text": "The origin of Alu-derived minisatellites appears to have been mediated by short flanking repeats, as first proposed by Haber and Louis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16343813", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1327, "text": "Finally, we propose that the origin of Alu subfamilies in human populations may be related to evolution of chromosome Y.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12167372", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 536, "text": "Our analysis indicates that about 60 Myr ago, before the prosimian divergence, free left and right monomers formed an Alu heterodimer connected by a 19-nucleotide-long A-rich linker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9694666", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 844, "text": "the presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric element", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8576966", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 326, "text": "Alu elements are each a dimer of similar, but not identical, fragments of total size about 300 bp, and originate from the 7SL RNA gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12815945", "endSection": "abstract" } ] }, { "body": "Abnormality in which vertebral region is important in the Bertolotti's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11154546", "http://www.ncbi.nlm.nih.gov/pubmed/23969004", "http://www.ncbi.nlm.nih.gov/pubmed/2533403", "http://www.ncbi.nlm.nih.gov/pubmed/16943469", "http://www.ncbi.nlm.nih.gov/pubmed/23096483", "http://www.ncbi.nlm.nih.gov/pubmed/8457417", "http://www.ncbi.nlm.nih.gov/pubmed/21511940", "http://www.ncbi.nlm.nih.gov/pubmed/24156003", "http://www.ncbi.nlm.nih.gov/pubmed/19830065", "http://www.ncbi.nlm.nih.gov/pubmed/18596536", "http://www.ncbi.nlm.nih.gov/pubmed/19547821", "http://www.ncbi.nlm.nih.gov/pubmed/19646556", "http://www.ncbi.nlm.nih.gov/pubmed/19037900", "http://www.ncbi.nlm.nih.gov/pubmed/20624239" ], "triples": [ { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13767955", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/14432659", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13716899", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13700654", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13305927", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/14445302", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13580681", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/14902269", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13642924", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/20254848", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13574281", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/14493837", "o": "http://linkedlifedata.com/resource/pubmed/keyword/LUMBOSACRAL+REGION%2Fabnormalities" } ], "ideal_answer": [ "Lumbosacral vertebral region is implicated in the Bertolotti's syndrome. Lumbosacral transitional vertebra is an anatomical variation of the fifth lumbar vertebra in which an enlarged transverse process can form a joint or fusion with the sacrum or ilium. Patients often complain of intractable sciatica that arises from impingement of the nerve root extraforaminally by compression caused by the enlarged transverse process." ], "exact_answer": [ "lumbosacral" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013131", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "factoid", "id": "5313058de3eabad02100000e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 155, "text": "Bertolotti's syndrome (BS), a form of lumbago in lumbosacral transitional vertebrae, is an important cause of low back pain in young patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24156003", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 850, "text": " Common causes of back pain were the ipsilateral L5-S1 facet joint, neoarticulation, the SI joint, and disc degeneration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24156003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Patients with Bertolotti's syndrome have characteristic lumbosacral anomalies and often have severe sciatica. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21511940", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 475, "text": "We suggest that the intractable sciatica in this syndrome could arise from impingement of the nerve root extraforaminally by compression caused by the enlarged transverse process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21511940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Radiofrequency sensory ablation as a treatment for symptomatic unilateral lumbosacral junction pseudarticulation (Bertolotti's syndrome): a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624239", "endSection": "title" }, { "offsetInBeginSection": 410, "offsetInEndSection": 534, "text": "She was found to have an elongated right L5 transverse process that articulated with the sacral ala (Bertolotti's syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624239", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 348, "text": "Lumbosacral transitional vertebra is an anatomical variation of the fifth lumbar vertebra in which an enlarged transverse process can form a joint or fusion with the sacrum or ilium. The association of that variant with low back pain and the change in the biomechanical properties of the lumbar spine is called Bertolotti's syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830065", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 703, "text": "Radiographic investigation revealed an anomalous enlargement of the left transverse process of the fifth lumbar vertebra forming a pseudarthrosis with the infrajacent ala of the sacrum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Transitional lumbosacral vertebrae and low back pain: diagnostic pitfalls and management of Bertolotti's syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19547821", "endSection": "title" }, { "offsetInBeginSection": 10, "offsetInEndSection": 227, "text": " Bertolotti's syndrome is a spine disorder characterized by the occurrence of a congenital lumbar transverse mega-apophysis in a transitional vertebral body that usually articulates with the sacrum or the iliac bone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19547821", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 488, "text": "It is characterized by an enlarged transverse process at the most caudal lumbar vertebra with a pseudoarticulation of the transverse process and the sacral ala. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18596536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Bertolotti's syndrome is characterised by anomalous enlargement of the transverse process(es) of the most caudal lumbar vertebra which may articulate or fuse with the sacrum or ilium and cause isolated L4/5 disc disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16943469", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 184, "text": "Case report of surgically treated mechanical low back pain from the facet joint contralateral to a unilateral anomalous lumbosacral articulation (Bertolotti's syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154546", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 624, "text": "Bertolotti's syndrome is mechanical low back pain associated with these transitional segments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154546", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1087, "text": "Repeated fluoroscopically guided injections implicated a symptomatic L6-S1 facet joint contralateral to an anomalous lumbosacral articulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "We surgically treated 16 patients with Bertolotti's syndrome (chronic, persistent low back pain and radiographically diagnosed transitional lumbar vertebra).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8457417", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 76, "text": "Transitional vertebrae of the lumbar spine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2533403", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Bertolotti's syndrome refers to the association of back pain with lumbosacral transitional vertebrae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2533403", "endSection": "abstract" } ] }, { "body": "What does iBAQ stand for in proteomic analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23794183", "http://www.ncbi.nlm.nih.gov/pubmed/22771841", "http://www.ncbi.nlm.nih.gov/pubmed/23981693" ], "ideal_answer": [ "iBAQ stands for intensity-based absolute quantification." ], "exact_answer": [ "intensity-based absolute quantification" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "factoid", "id": "5348307daeec6fbd07000011", "snippets": [ { "offsetInBeginSection": 674, "offsetInEndSection": 720, "text": "intensity-based absolute quantification (iBAQ)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23981693", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 750, "text": "Intensity-Based Absolute Quantification Index,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23794183", "endSection": "abstract" } ] }, { "body": "Which is the main target of the anti-arrhythmic activity of flecainide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23334259", "http://www.ncbi.nlm.nih.gov/pubmed/25274603", "http://www.ncbi.nlm.nih.gov/pubmed/23558880", "http://www.ncbi.nlm.nih.gov/pubmed/24614665", "http://www.ncbi.nlm.nih.gov/pubmed/24510469", "http://www.ncbi.nlm.nih.gov/pubmed/24917414", "http://www.ncbi.nlm.nih.gov/pubmed/24858181" ], "ideal_answer": [ "Flecainide is a class 1c antiarrhythmic that acts by blocking sodium channels and is used mainly in the treatment of supraventricular arrhythmias." ], "exact_answer": [ "The sodium channel" ], "concepts": [ "http://www.biosemantics.org/jochem#4249323" ], "type": "factoid", "id": "54da32bc0f63c58e6e000001", "snippets": [ { "offsetInBeginSection": 728, "offsetInEndSection": 764, "text": "flecainide (sodium channel blocker) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24858181", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 326, "text": "Flecainide is a sodium channel blocker with minimal effects expected on ventricular repolarization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510469", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 269, "text": "Flecainide, a class I antiarrhythmic drug, inhibits Na(+) and RyR2 channels and prevents CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25274603", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 196, "text": " flecainide, a Class I antiarrhythmic drug, improves left ventricular pressure gradient (LVPG) or symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24917414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Flecainide is a class 1c antiarrhythmic that acts by blocking sodium channels to reduce intracardiac conduction and is used mainly in the treatment of supraventricular arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24614665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Flecainide is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23558880", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1619, "text": "Flecainide reduces spark and wave frequency in the intact rat cardiomyocyte at therapeutically relevant concentrations but the mechanism involves I(Na) reduction rather than direct ryanodine receptor (RyR2) inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334259", "endSection": "abstract" } ] }, { "body": "Does thyroid hormone affect cardiac remodeling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18455802", "http://www.ncbi.nlm.nih.gov/pubmed/20926779", "http://www.ncbi.nlm.nih.gov/pubmed/23820669", "http://www.ncbi.nlm.nih.gov/pubmed/23532677", "http://www.ncbi.nlm.nih.gov/pubmed/17560116", "http://www.ncbi.nlm.nih.gov/pubmed/22039709", "http://www.ncbi.nlm.nih.gov/pubmed/22134702", "http://www.ncbi.nlm.nih.gov/pubmed/18430565", "http://www.ncbi.nlm.nih.gov/pubmed/18622044", "http://www.ncbi.nlm.nih.gov/pubmed/20730619", "http://www.ncbi.nlm.nih.gov/pubmed/16499159", "http://www.ncbi.nlm.nih.gov/pubmed/20668933", "http://www.ncbi.nlm.nih.gov/pubmed/17389455", "http://www.ncbi.nlm.nih.gov/pubmed/18274800", "http://www.ncbi.nlm.nih.gov/pubmed/17024559", "http://www.ncbi.nlm.nih.gov/pubmed/21568669", "http://www.ncbi.nlm.nih.gov/pubmed/23555069", "http://www.ncbi.nlm.nih.gov/pubmed/20560106", "http://www.ncbi.nlm.nih.gov/pubmed/18773293", "http://www.ncbi.nlm.nih.gov/pubmed/22403173", "http://www.ncbi.nlm.nih.gov/pubmed/19951746", "http://www.ncbi.nlm.nih.gov/pubmed/21159857", "http://www.ncbi.nlm.nih.gov/pubmed/19826181" ], "ideal_answer": [ "TH affects cardiac remodeling" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963" ], "type": "yesno", "id": "52efc041c8da89891000001b", "snippets": [ { "offsetInBeginSection": 1161, "offsetInEndSection": 1356, "text": "The aim of this brief paper is to highlight new developments in understanding the cardioprotective role of thyroid hormone in reverting regulatory networks involved in adverse cardiac remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Thyroid hormone receptor \u03b11 (TR\u03b11) is shown to be critical for the maturation of cardiomyocytes and for the cellular response to stress. TR\u03b11 is altered during post ischemic cardiac remodeling but the physiological significance of this response is not fully understood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23532677", "endSection": "abstract" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1581, "text": "AMI induces downregulation of thyroid hormone signaling and pharmacological inhibition of TR\u03b11 further depresses post-ischemic cardiac function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23532677", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1219, "text": "These findings reveal crucial roles for Dio3 in heart function and remodeling, which may have pathophysiologic implications for human restrictive cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403173", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1661, "text": "TH administration after AMI prevented tissue hypothyroidism and resulted in decreased beta-MHC expression, increased wall thickening and normalized wallstress, while stretch-induced p38 MAPK activation was increased. We conclude that diabetes exacerbates post-ischemic cardiac remodeling and that tissue hypothyroidism may be involved in this response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22039709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730619", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730619", "endSection": "abstract" }, { "offsetInBeginSection": 1768, "offsetInEndSection": 1965, "text": "Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730619", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 567, "text": "TH affects cardiac remodeling by limiting reperfusion injury, and, at later states, by inducing distinct changes in cardiac chamber geometry in a time-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20668933", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 715, "text": "Furthermore, administration of TH can convert pathologic to physiologic hypertrophy. These effects are the result of favorable cellular remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20668933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Thyroid hormone (TH) is critical in cardiac cell differentiation (regulating contractile proteins and cell geometry) and this effect could be potentially exploited therapeutically in reversing the process of de-differentiation which underlies postischemic cardiac remodeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19826181", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1549, "text": "TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19826181", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 636, "text": "Changes in thyroid hormone (TH)-TH receptors (TRs) axis occur in the course of post-infarction cardiac remodeling and seem to contribute to cardiac fetal phenotype. TH can \"rebuild\" the post-infarcted heart by preventing the fetal-like pattern of contractile proteins expression, normalizing wall tension, and optimizing cardiac chamber geometry. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18773293", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 342, "text": "TH, apart from its \"classical\" actions on cardiac contractility and heart rhythm, appears to regulate various intracellular signaling pathways related to stress responses and cardiac remodelling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18455802", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 883, "text": "More importantly, experimental and clinical studies demonstrate that TH can limit ischaemic injury, attenuate cardiac remodeling and improve cardiac hemodynamics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18455802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560116", "endSection": "title" }, { "offsetInBeginSection": 1987, "offsetInEndSection": 2121, "text": "Thyroid hormone administration early after infarction attenuates cardiac remodeling and significantly improves myocardial performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "It has previously been shown that thyroid hormone can reverse cardiac remodeling in failing hearts by reducing myocardial wall stress due to the unique changes induced in cardiac myocyte shape. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17024559", "endSection": "abstract" } ] }, { "body": "What is the effect of ROS on cyclin B1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23567243", "http://www.ncbi.nlm.nih.gov/pubmed/22147197", "http://www.ncbi.nlm.nih.gov/pubmed/24296129", "http://www.ncbi.nlm.nih.gov/pubmed/18023967", "http://www.ncbi.nlm.nih.gov/pubmed/20444961", "http://www.ncbi.nlm.nih.gov/pubmed/19331169", "http://www.ncbi.nlm.nih.gov/pubmed/17671211", "http://www.ncbi.nlm.nih.gov/pubmed/24147344", "http://www.ncbi.nlm.nih.gov/pubmed/24064966", "http://www.ncbi.nlm.nih.gov/pubmed/20446899", "http://www.ncbi.nlm.nih.gov/pubmed/22834967" ], "ideal_answer": [ "Reactive oxygen species (ROS) production is able to cause growth arrest at the G2-M checkpoint of the cell cycle, partly by deregulation of Cyclin B1 expression." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1901033", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1901032", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097125", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016213", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056744", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000302" ], "type": "summary", "id": "53175e68b166e2b806000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 484, "text": "The present study was undertaken to determine whether sulforaphane-derived reactive oxygen species (ROS) might cause growth arrest and apoptosis in human bladder cancer 5637 cells. Our results show that the reduced viability of 5637 cells by sulforaphane is due to mitotic arrest, but not the G2 phase. The sulforaphane-induced mitotic arrest correlated with an induction of cyclin B1 and phosphorylation of Cdk1, as well as a concomitant increased complex between cyclin B1 and Cdk1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24296129", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 759, "text": "Further mechanistic studies revealed that induction of apoptosis is associated with cell cycle arrest at G2/M phase, increased generation of reactive oxygen species (ROS), reduced mitochondrial membrane potential (MMP), release of cytochrome c (Cyto c) and apoptosis inducing factor (AIF) from mitochondria to cytosol, upregulation of Bax, p21 and p53, and down-regulation of Bcl-2, cyclin B1 and cyclin-dependent kinase 1 (CDK1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24147344", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1240, "text": "LDH inhibition by oxamate induced G2/M cell cycle arrest via downregulation of the CDK1/cyclin B1 pathway and promoted apoptosis through enhancement of mitochondrial ROS generation. N-acetylcysteine, a specific scavenger of ROS, significantly blocked the growth inhibition effect induced by oxamate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24064966", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 392, "text": "As well as DICO induced G2/M cell cycle arrest and apoptosis via a ROS-mediated mitochondrial pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567243", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 695, "text": "Meanwhile, the alterations of cyclin A and B1, p-CDK1 and p-cdc25c levels were also observed in response to DICO treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567243", "endSection": "abstract" }, { "offsetInBeginSection": 1173, "offsetInEndSection": 1455, "text": "Butyrate (> 2 mm) inhibited the expression of cdc2, cdc25C and cyclinB1 mRNAs and reduced the levels of Cdc2, Cdc25C and cyclinB1 proteins in GFs, as determined using RT-PCR and western blotting, respectively. This toxic effect of butyrate was associated with the production of ROS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22834967", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 970, "text": "Furthermore, costunolide induced cell cycle arrest in the G2/M phase via decrease in Cdc2, cyclin B1 and increase in p21WAF1 expression,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147197", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1136, "text": "In addition, costunolide had a slight induced effect on ROS generation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147197", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 472, "text": "This study suggested that G2/M cell cycle arrest was triggered by ROS/NO productions with regulations of p53, p21, cell division cycle 25C (Cdc25C), Cdc2 and cyclin B1, which were able to be prevented by protein tyrosine kinase (PTK) activity inhibitor genistein or JNK inhibitor SP600125.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20446899", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 646, "text": "Other G(2)/M regulatory molecules such as Cdc25C, Cdk1, cyclin B1 were down-regulated by DIM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20444961", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1532, "text": "Blocking ROS generation by N-acetyl cysteine protects the cells from DIM-mediated G(2)/M arrest and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20444961", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1404, "text": "Taken together, these findings suggest that emodin mediated oxidative injury (DNA damage) based on ROS production and ER stress based on the levels of GADD153 and GRP78 that acts as an early and upstream change in the cell death cascade to caspase- and mitochondria-dependent signaling pathways, triggers mitochondrial dysfunction from Bcl-2 and Bax modulation, mitochondrial cytochrome c release and caspase activation, consequently leading to apoptosis in SCC-4 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19331169", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 422, "text": "In this study, treatment of human tongue cancer SCC-4 cells with various concentrations of emodin led to G2/M arrest through promoted p21 and Chk2 expression but inhibited cyclin B1 and cdc2;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19331169", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 473, "text": "Further investigation revealed that plumbagin's inhibition of cell growth was also evident in a nude mice model. Blockade of cell cycle was associated with increased levels of p21, and reduced amounts of cyclin B1, cyclin A, Cdc2, and Cdc25C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18023967", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 793, "text": "We also found the generation of ROS is a critical mediator in plumbagin-induced cell growth inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18023967", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 500, "text": "IOA exhibited effective cell growth inhibition by inducing cancer cells to undergo G(2)-M phase arrest and apoptosis. Further investigation revealed that IOA's inhibition of cell growth was also evident in a nude mice model. Cell cycle blockade was associated with increased levels of p21 and reduced amounts of cyclin B1, cyclin A, cdc2, and cdc25C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671211", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 902, "text": "We also found that the generation of reactive oxygen species (ROS) is a critical mediator in IOA-induced cell growth inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671211", "endSection": "abstract" } ] }, { "body": "Are there any HCV replication inhibitors available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23791700", "http://www.ncbi.nlm.nih.gov/pubmed/23466233", "http://www.ncbi.nlm.nih.gov/pubmed/23440335", "http://www.ncbi.nlm.nih.gov/pubmed/23629709", "http://www.ncbi.nlm.nih.gov/pubmed/24154738", "http://www.ncbi.nlm.nih.gov/pubmed/23453230", "http://www.ncbi.nlm.nih.gov/pubmed/21694902", "http://www.ncbi.nlm.nih.gov/pubmed/23896281", "http://www.ncbi.nlm.nih.gov/pubmed/24165192", "http://www.ncbi.nlm.nih.gov/pubmed/23745769", "http://www.ncbi.nlm.nih.gov/pubmed/23230455", "http://www.ncbi.nlm.nih.gov/pubmed/23431163", "http://www.ncbi.nlm.nih.gov/pubmed/23384816", "http://www.ncbi.nlm.nih.gov/pubmed/23454058", "http://www.ncbi.nlm.nih.gov/pubmed/23688081", "http://www.ncbi.nlm.nih.gov/pubmed/23896953", "http://www.ncbi.nlm.nih.gov/pubmed/21331152" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/24334", "o": "Drug" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/24334", "o": "Intervention #24334 (Drug:HCV polymerase inhibitor pro-drug)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/24334", "o": "HCV polymerase inhibitor pro-drug" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10759582", "o": "Drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/23449", "o": "Drug" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/23449", "o": "Intervention #23449 (Drug:HCV polymerase inhibitor pro-drug)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/23449", "o": "HCV polymerase inhibitor pro-drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/26936", "o": "Drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/26936", "o": "HCV polymerase inhibitor pro-drug" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/26936", "o": "Intervention #26936 (Drug:HCV polymerase inhibitor pro-drug)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/28754", "o": "Drug" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/28754", "o": "Intervention #28754 (Drug:HCV polymerase inhibitor pro-drug)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/28754", "o": "HCV polymerase inhibitor pro-drug" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_type", "s": "http://data.linkedct.org/resource/intervention/24333", "o": "Drug" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/24333", "o": "Intervention #24333 (Drug:HCV polymerase inhibitor pro-drug)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/24333", "o": "HCV polymerase inhibitor pro-drug" } ], "ideal_answer": [ "Chronic hepatitis C virus (HCV) infection is a worldwide health problem causing serious complications, such as liver cirrhosis and hepatoma. Small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) have been reported to suppress gene expression significantly. HCV seems a suitable candidate for targets of siRNAs, as HCV is a positive single-strand RNA virus and replicates in the cytoplasm. Based on results, nowadays there are few HCV replication inhibitors such as GS-563253, PSI-6130, NA-808, BMS-790052, GS-9132 and BMS-788329." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014779", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ], "type": "yesno", "id": "53353927d6d3ac6a34000043", "snippets": [ { "offsetInBeginSection": 778, "offsetInEndSection": 925, "text": "We report here the discovery of the first small-molecule HCV infectivity inhibitor, GS-563253, also called HCV infectivity inhibitor 1 (HCV II-1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165192", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "Resistance to mericitabine (prodrug of HCV NS5B polymerase inhibitor PSI-6130) is rare and conferred by the NS5B S282T mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24154738", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 616, "text": "We tested the ability of NA808 to inhibit SPT's enzymatic activity in FLR3-1 replicon cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23791700", "endSection": "abstract" }, { "offsetInBeginSection": 1488, "offsetInEndSection": 1631, "text": "The SPT inhibitor NA808 prevents replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in cultured hepatocytes and in mice with humanized livers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23791700", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 263, "text": "Vaniprevir (phase III clinical trials) and MK-5172 (phase II clinical trials) are two potent antiviral compounds that target NS3/4A protease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23745769", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 200, "text": "treatment for hepatitis C virus (HCV) infection has been significantly improved with the approval of the first two HCV NS3/4A protease inhibitors, telaprevir (Incivek) and boceprevir (Victrelis). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688081", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 1271, "text": "Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23896953", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 240, "text": "HCV NS5A replication complex inhibitors, exemplified by Daclatasvir (BMS-790052), represent a new class of DAA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23896281", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 265, "text": "ACH-806 (or GS-9132) is a novel, small-molecule inhibitor specific for hepatitis C virus (HCV). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23629709", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 329, "text": "Telaprevir and boceprevir are the first two protease inhibitor (PI) DAAs to be approved for combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23453230", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 130, "text": "symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466233", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1204, "text": "In vitro, boceprevir is more active than telaprevir against the HCV G3 NS3/4A enzyme in cell-based and biochemical assays and against G3 isolates in replicon assays", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23454058", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 577, "text": "Alisporivir is the most advanced host-targeting antiviral in clinical development. Alisporivir blocks HCV replication by neutralizing the peptidyl-prolyl isomerase activity of the abundant host cytosolic protein, cyclophilin A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23440335", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 264, "text": "Interestingly, the NS5A inhibitor daclatasvir (BMS-790052) caused a decrease in serum HCV RNA levels by about two orders of magnitude within 6 h of administration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23431163", "endSection": "abstract" } ] }, { "body": "Provide examples of how molecular transporters contribute to multi-drug resistance in bacteria.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23746717", "http://www.ncbi.nlm.nih.gov/pubmed/24056102", "http://www.ncbi.nlm.nih.gov/pubmed/23755047", "http://www.ncbi.nlm.nih.gov/pubmed/22053181", "http://www.ncbi.nlm.nih.gov/pubmed/24123816", "http://www.ncbi.nlm.nih.gov/pubmed/24297686", "http://www.ncbi.nlm.nih.gov/pubmed/16290174", "http://www.ncbi.nlm.nih.gov/pubmed/23894076", "http://www.ncbi.nlm.nih.gov/pubmed/23870163", "http://www.ncbi.nlm.nih.gov/pubmed/24014018", "http://www.ncbi.nlm.nih.gov/pubmed/23742803" ], "ideal_answer": [ "MDR efflux pumps began causing clinical problems relatively recently, in parallel with the extensive use of antibiotics in medicine and as supplements in animal feeds. However, our analyses indicate that these MDR efflux pumps did not arise through recent mutations in genes encoding transporters that changed their substrate specificities.\n\nInstead, such MDR pumps are encoded within the genomes of virtually all microorganisms, so these genes are present and thus need only to be activated to become problematic. Moreover, lateral transfer of genes among bacteria has occurred frequently, particularly for plasmid-encoded systems, suggesting that such genes can be acquired fairly readily even if they are not initially present. Finally, although mutations that enable transporters to act on different types of substrate are rare, experiments and phylogenetic analyses indicate that simple point mutations can readily narrow or broaden a particular transporter's specificity toward a single class of compounds (e.g., sugars, amino acids, or drugs)." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008559", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042493", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0015238", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024881", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004351", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004352", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0015893", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006810", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2001023", "http://www.uniprot.org/uniprot/RDR1_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009816", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090484", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006855", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024901", "http://www.biosemantics.org/jochem#4264759", "http://www.uniprot.org/uniprot/PDR1_YEAST", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2001025", "http://www.uniprot.org/uniprot/AB29G_ARATH", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2001024", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001419" ], "type": "summary", "id": "52ed264a98d023950500002f", "snippets": [ { "offsetInBeginSection": 123, "offsetInEndSection": 298, "text": " One of the common mechanisms of multidrug resistance in eukaryotic cells is the active efflux of a broad range of xenobiotics through ATP-binding cassette (ABC) transporters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297686", "endSection": "abstract" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 2042, "text": "Overall, the phylogenetic diversity of As-resistant bacteria in underground water was very limited if compared with lentic and lotic waters. Lastly, our molecular data support the hypothesis that the horizontal gene transfer of ars in As-containing freshwater environments is not limited to closely-related genomes, but also occurs between bacteria that are distant from an evolutionary viewpoint, thereby indicating that such genetic events may be considered a source of microbial resistance to arsenic-toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23870163", "endSection": "abstract" }, { "offsetInBeginSection": 1511, "offsetInEndSection": 1729, "text": "We postulate that the RND transporter All3143 and the predicted membrane fusion protein All3144, as homologs of E. coli AcrB and AcrA, respectively, are major players for antibiotic resistance in Anabaena sp. PCC 7120.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24014018", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1347, "text": "These observations suggest a physiological association between c-di-AMP and the MDR transporters and support the model that MDR transporters mediate c-di-AMP secretion to regulate peptidoglycan synthesis in response to cell wall stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056102", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1686, "text": "Our data suggest that SmbFT truly displays immunity function and confer protection against Smb and structurally similar lantibiotics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24123816", "endSection": "abstract" }, { "offsetInBeginSection": 1262, "offsetInEndSection": 1487, "text": "This study indicates that the tetA gene decreases sensitivity to tigecycline in Salmonella spp. at a low level. With additional resistance mechanisms, tetA-carrying strains can reach the breakpoint for tigecycline resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746717", "endSection": "abstract" }, { "offsetInBeginSection": 1704, "offsetInEndSection": 1894, "text": "Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gram-negative clinical isolates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742803", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 257, "text": "(RND)-type efflux transporters play the main role in intrinsic resistance to various antimicrobial agents in many gram-negative bacteria. Here, we estimated 12 RND-type efflux transporter genes in Vibrio parahaemolyticus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894076", "endSection": "abstract" } ] }, { "body": "What is the minimal genome build?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21203957", "http://www.ncbi.nlm.nih.gov/pubmed/23420643", "http://www.ncbi.nlm.nih.gov/pubmed/23219343", "http://www.ncbi.nlm.nih.gov/pubmed/26539175", "http://www.ncbi.nlm.nih.gov/pubmed/21987714", "http://www.ncbi.nlm.nih.gov/pubmed/23873957", "http://www.ncbi.nlm.nih.gov/pubmed/22916492" ], "ideal_answer": [ "The identification of the essential genes of bacteria and the minimal genome for the free-living cellular life could provide insights into the origin, evolution, and essence of life forms. The field of Synthetic Biology seeks to apply engineering principles to biology in order to produce novel biological systems. One approach to accomplish this goal is the genome-driven cell engineering approach, which searches for functioning minimal genomes in naturally occurring microorganisms, which can then be used as a template for future systems. Currently a prototypical minimal genome has not been discovered." ], "type": "summary", "id": "56f82f9acf1c325851000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 458, "text": "As a key focus of synthetic biology, building a minimal artificial cell has given rise to many discussions. A synthetic minimal cell will provide an appropriate chassis to integrate functional synthetic parts, devices and systems with functions that cannot generally be found in nature. The design and construction of a functional minimal genome is a key step while building such a cell/chassis since all the cell functions can be traced back to the genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21203957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 419, "text": "The field of Synthetic Biology seeks to apply engineering principles to biology in order to produce novel biological systems. One approach to accomplish this goal is the genome-driven cell engineering approach, which searches for functioning minimal genomes in naturally occurring microorganisms, which can then be used as a template for future systems. Currently a prototypical minimal genome has not been discovered. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21987714", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 266, "text": "The identification of the essential genes of bacteria and the minimal genome for the free-living cellular life could provide insights into the origin, evolution, and essence of life forms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22916492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Minimal bacterial gene set comprises the genetic elements needed for survival of engineered bacterium on a rich medium. This set is estimated to include 300-350 protein-coding genes. One way of simplifying an organism with such a minimal genome even further is to constrain the amino acid content of its proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23873957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "A central undertaking in synthetic biology (SB) is the quest for the 'minimal genome'. However, 'minimal sets' of essential genes are strongly context-dependent and, in all prokaryotic genomes sequenced to date, not a single protein-coding gene is entirely conserved. Furthermore, a lack of consensus in the field as to what attributes make a gene truly essential adds another aspect of variation. Thus, a universal minimal genome remains elusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23219343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts-list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the last universal common ancestor, as few genes trace back to this hypothetical ancestral state. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26539175", "endSection": "abstract" } ] }, { "body": "Is cocaine use associated with increased risk for intracerebral hemorrhage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7774897", "http://www.ncbi.nlm.nih.gov/pubmed/8628469", "http://www.ncbi.nlm.nih.gov/pubmed/11456006", "http://www.ncbi.nlm.nih.gov/pubmed/2909100", "http://www.ncbi.nlm.nih.gov/pubmed/10696649", "http://www.ncbi.nlm.nih.gov/pubmed/20645024", "http://www.ncbi.nlm.nih.gov/pubmed/7801738", "http://www.ncbi.nlm.nih.gov/pubmed/2742464", "http://www.ncbi.nlm.nih.gov/pubmed/20185779", "http://www.ncbi.nlm.nih.gov/pubmed/20444626", "http://www.ncbi.nlm.nih.gov/pubmed/7482637", "http://www.ncbi.nlm.nih.gov/pubmed/20456585", "http://www.ncbi.nlm.nih.gov/pubmed/7701492", "http://www.ncbi.nlm.nih.gov/pubmed/14504335", "http://www.ncbi.nlm.nih.gov/pubmed/9122836", "http://www.ncbi.nlm.nih.gov/pubmed/9173019", "http://www.ncbi.nlm.nih.gov/pubmed/12764233", "http://www.ncbi.nlm.nih.gov/pubmed/2492650", "http://www.ncbi.nlm.nih.gov/pubmed/8754572", "http://www.ncbi.nlm.nih.gov/pubmed/1623099" ], "ideal_answer": [ "Cocaine use is associated with increased incidence of intracranial hemorrhages most likely due to pressure increases." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003042", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020300", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013345", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019970", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016578", "http://www.disease-ontology.org/api/metadata/DOID:809" ], "type": "yesno", "id": "5159b990d24251bc050000a3", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 71, "text": "Stroke in crack-cocaine abusers is increasingly recognized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20645024", "endSection": "sections.0" }, { "offsetInBeginSection": 533, "offsetInEndSection": 1137, "text": "There were significant differences between crack-cocaine cases and controls in age (48.7 years vs. 55 years) (P = 0.0001), male gender (65.6% vs. 40.9%) (odds ratios, OR = 1.64, 95% CI 1.22-2.21), arterial hypertension (61.1% vs. 83.9%) (OR = 0.30, 95% CI 0.15-0.60), hypercholesterolemia (18.7% vs. 68.5%) (OR = 0.10, 95% CI 0.05-0.21), diabetes (20.9% vs. 41.9%) (OR = 0.36, 95% CI 0.19-0.70), cigarette smoking (70.6% vs. 29%) (OR = 5.86, 95% CI 3.07-11.20), ischemic stroke (61.3% vs. 79.6%) (OR = 0.40, 95% CI 0.21-0.78), and intracerebral hemorrhage (33.3% vs. 17.2%) (OR = 3.03, 95% CI 1.53-6.00).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20645024", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Intracerebral hemorrhage (ICH) is a well-recognized complication of recreational cocaine use.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20456585", "endSection": "sections.0" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1718, "text": "ICH is more common in those currently using cocaine perhaps because of acute spikes in blood pressure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20444626", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Intracerebral hemorrhage in cocaine users.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185779", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 196, "text": "Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185779", "endSection": "sections.0" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1772, "text": "Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12764233", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Cocaine use and hypertension are major risk factors for intracerebral hemorrhage in young African Americans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11456006", "endSection": "title" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1026, "text": "Cocaine use (OR 6.1, 95% CI 3.3-11.8), hypertension (OR 5.2, 95% CI 3.2-8.7) and alcohol use (OR 1.9, 95% CI 1.1-3.3) were independently associated with increased risk for ICH", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11456006", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "Cocaine use has been temporally associated with neurovascular complications, including the rupture of intracerebral aneurysms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9122836", "endSection": "sections.0" }, { "offsetInBeginSection": 1892, "offsetInEndSection": 2076, "text": "Chronic cocaine use appears to predispose patients who harbor incidental neurovascular anomalies to present at an earlier point in their natural history than similar non-cocaine users.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9122836", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Acute intoxication with either cocaine or methamphetamine may contribute to formation and rupture of a berry aneurysm by causing transient hypertension and tachycardia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8754572", "endSection": "sections.0" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1364, "text": "Although the exact mechanism by which berry aneurysms form remains undetermined, research indicates that propagation and rupture of the aneurysm are aggravated by hypertension and tachycardia, both of which are pharmacologic side effects of cocaine and methamphetamine", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8754572", "endSection": "sections.0" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1336, "text": "The high frequency of hypertension, hypertensive intracerebral hemorrhage, and lacunar infarction among young black patients with stroke suggests accelerated hypertensive arteriolar damage, possibly due to poor control of hypertension.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7482637", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Cocaine induced intracerebral hemorrhage: analysis of predisposing factors and mechanisms causing hemorrhagic strokes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7774897", "endSection": "title" }, { "offsetInBeginSection": 195, "offsetInEndSection": 427, "text": "hypertensive cardiovascular disease (HCVD) was significantly higher in persons with intracerebral hemorrhage than in those with aneurysm rupture. Our findings suggest that HCVD predisposes to cocaine induced intracerebral hemorrhage", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7774897", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Intracerebral hemorrhage associated with cocaine abuse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2742464", "endSection": "title" }, { "offsetInBeginSection": 383, "offsetInEndSection": 527, "text": "n view of the present epidemic of cocaine abuse, cocaine toxicity should be considered in the differential diagnosis of intracerebral hemorrhage", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2742464", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "An increase in cocaine abuse by pregnant women has been associated with a range of maternal/fetal cardiovascular complications. Intracerebral hemorrhage has been reported as a cocaine-related complication,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2492650", "endSection": "sections.0" }, { "offsetInBeginSection": 50, "offsetInEndSection": 348, "text": "13 patients were identified with neurologic deficits attributable to the use of cocaine. Ischemic manifestations were the most frequent, occurring in seven (54%) patients, with a mean age of 34.2 years. Three (23%) patients had subarachnoid hemorrhage, and three (23%) had intracerebral hemorrhage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2909100", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "OBJECTIVE: An association between cocaine use and stroke has been reported, but few studies have examined cocaine-related neurovascular disease using modern stroke diagnostic techniques.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20444626", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "OBJECTIVE: Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185779", "endSection": "sections.0" }, { "offsetInBeginSection": 253, "offsetInEndSection": 437, "text": "Because cocaine and ecstasy abuse has been reported to be a risk factor for ischemic stroke and fatal brain hemorrhage, thromboaspiration may be an alternative therapy to thrombolysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14504335", "endSection": "sections.0" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1772, "text": "CONCLUSIONS: Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12764233", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "OBJECTIVE: The use of cocaine has been increasingly associated with cerebrovascular disease specially in young adults.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10696649", "endSection": "sections.0" }, { "offsetInBeginSection": 132, "offsetInEndSection": 311, "text": "Cocaine hydrochloride causes mainly intracerebral and subarachnoidal bleeding, while crack (freebase) causes intracranial hemorrhage and ischemic infarctions with equal frequency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9173019", "endSection": "sections.0" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1054, "text": "CONCLUSIONS: These findings implicate cocaine use as a significant risk factor for fatal brain hemorrhage and may explain, in part, the increased incidence of hemorrhagic stroke in some drug-using cohorts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8628469", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Abuse of amphetamine, cocaine and related compounds has become an important risk factor for intracerebral haemorrhage in young adults.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7701492", "endSection": "sections.0" }, { "offsetInBeginSection": 507, "offsetInEndSection": 603, "text": "Strokes occurred within 3 h of cocaine use in 15 patients with infarcts and 17 with hemorrhages.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7801738", "endSection": "sections.0" }, { "offsetInBeginSection": 158, "offsetInEndSection": 316, "text": "We present three cases of intracerebral hemorrhage which occurred after cocaine consumption (intranasal route in two cases and intravenous route in one case).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1623099", "endSection": "sections.0" } ] }, { "body": "Is miR-21 related to carcinogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16778182", "http://www.ncbi.nlm.nih.gov/pubmed/21882851", "http://www.ncbi.nlm.nih.gov/pubmed/18719201", "http://www.ncbi.nlm.nih.gov/pubmed/19509156", "http://www.ncbi.nlm.nih.gov/pubmed/20702469", "http://www.ncbi.nlm.nih.gov/pubmed/23288924", "http://www.ncbi.nlm.nih.gov/pubmed/20978195", "http://www.ncbi.nlm.nih.gov/pubmed/22291592", "http://www.ncbi.nlm.nih.gov/pubmed/21646541", "http://www.ncbi.nlm.nih.gov/pubmed/19748927", "http://www.ncbi.nlm.nih.gov/pubmed/22316494", "http://www.ncbi.nlm.nih.gov/pubmed/22610076", "http://www.ncbi.nlm.nih.gov/pubmed/23049818", "http://www.ncbi.nlm.nih.gov/pubmed/20309880", "http://www.ncbi.nlm.nih.gov/pubmed/19175831", "http://www.ncbi.nlm.nih.gov/pubmed/21279518", "http://www.ncbi.nlm.nih.gov/pubmed/19906824", "http://www.ncbi.nlm.nih.gov/pubmed/22528454", "http://www.ncbi.nlm.nih.gov/pubmed/19546886", "http://www.ncbi.nlm.nih.gov/pubmed/22709411", "http://www.ncbi.nlm.nih.gov/pubmed/19435529", "http://www.ncbi.nlm.nih.gov/pubmed/22265967", "http://www.ncbi.nlm.nih.gov/pubmed/20480266", "http://www.ncbi.nlm.nih.gov/pubmed/19473551", "http://www.ncbi.nlm.nih.gov/pubmed/23239859", "http://www.ncbi.nlm.nih.gov/pubmed/23239858", "http://www.ncbi.nlm.nih.gov/pubmed/18853072", "http://www.ncbi.nlm.nih.gov/pubmed/22678116", "http://www.ncbi.nlm.nih.gov/pubmed/23466817", "http://www.ncbi.nlm.nih.gov/pubmed/20682703", "http://www.ncbi.nlm.nih.gov/pubmed/18507035", "http://www.ncbi.nlm.nih.gov/pubmed/20827319", "http://www.ncbi.nlm.nih.gov/pubmed/22638884", "http://www.ncbi.nlm.nih.gov/pubmed/22747440", "http://www.ncbi.nlm.nih.gov/pubmed/20141427", "http://www.ncbi.nlm.nih.gov/pubmed/21494432", "http://www.ncbi.nlm.nih.gov/pubmed/23224068", "http://www.ncbi.nlm.nih.gov/pubmed/23416953", "http://www.ncbi.nlm.nih.gov/pubmed/23255093", "http://www.ncbi.nlm.nih.gov/pubmed/21880514", "http://www.ncbi.nlm.nih.gov/pubmed/18187804", "http://www.ncbi.nlm.nih.gov/pubmed/22072622", "http://www.ncbi.nlm.nih.gov/pubmed/18591254", "http://www.ncbi.nlm.nih.gov/pubmed/21883657", "http://www.ncbi.nlm.nih.gov/pubmed/22476768", "http://www.ncbi.nlm.nih.gov/pubmed/20620599", "http://www.ncbi.nlm.nih.gov/pubmed/21081469", "http://www.ncbi.nlm.nih.gov/pubmed/19641183", "http://www.ncbi.nlm.nih.gov/pubmed/21170291", "http://www.ncbi.nlm.nih.gov/pubmed/20380575", "http://www.ncbi.nlm.nih.gov/pubmed/21088996", "http://www.ncbi.nlm.nih.gov/pubmed/23483606", "http://www.ncbi.nlm.nih.gov/pubmed/22322462", "http://www.ncbi.nlm.nih.gov/pubmed/20693987", "http://www.ncbi.nlm.nih.gov/pubmed/23175214", "http://www.ncbi.nlm.nih.gov/pubmed/16966691", "http://www.ncbi.nlm.nih.gov/pubmed/17587821", "http://www.ncbi.nlm.nih.gov/pubmed/22168593", "http://www.ncbi.nlm.nih.gov/pubmed/21350005", "http://www.ncbi.nlm.nih.gov/pubmed/18230780", "http://www.ncbi.nlm.nih.gov/pubmed/18089790", "http://www.ncbi.nlm.nih.gov/pubmed/20346171", "http://www.ncbi.nlm.nih.gov/pubmed/17475218", "http://www.ncbi.nlm.nih.gov/pubmed/22860003", "http://www.ncbi.nlm.nih.gov/pubmed/18451233", "http://www.ncbi.nlm.nih.gov/pubmed/19789312", "http://www.ncbi.nlm.nih.gov/pubmed/20483747", "http://www.ncbi.nlm.nih.gov/pubmed/20633539", "http://www.ncbi.nlm.nih.gov/pubmed/21406606", "http://www.ncbi.nlm.nih.gov/pubmed/22430134", "http://www.ncbi.nlm.nih.gov/pubmed/19730150", "http://www.ncbi.nlm.nih.gov/pubmed/19737943", "http://www.ncbi.nlm.nih.gov/pubmed/19901002", "http://www.ncbi.nlm.nih.gov/pubmed/22703586", "http://www.ncbi.nlm.nih.gov/pubmed/20338946", "http://www.ncbi.nlm.nih.gov/pubmed/22618808", "http://www.ncbi.nlm.nih.gov/pubmed/21532496", "http://www.ncbi.nlm.nih.gov/pubmed/22689922", "http://www.ncbi.nlm.nih.gov/pubmed/21468550", "http://www.ncbi.nlm.nih.gov/pubmed/20952761", "http://www.ncbi.nlm.nih.gov/pubmed/23481326", "http://www.ncbi.nlm.nih.gov/pubmed/22001440", "http://www.ncbi.nlm.nih.gov/pubmed/19682430", "http://www.ncbi.nlm.nih.gov/pubmed/23202912", "http://www.ncbi.nlm.nih.gov/pubmed/20221895", "http://www.ncbi.nlm.nih.gov/pubmed/23212265", "http://www.ncbi.nlm.nih.gov/pubmed/23335180", "http://www.ncbi.nlm.nih.gov/pubmed/23446999", "http://www.ncbi.nlm.nih.gov/pubmed/21102586", "http://www.ncbi.nlm.nih.gov/pubmed/23417858", "http://www.ncbi.nlm.nih.gov/pubmed/18372920", "http://www.ncbi.nlm.nih.gov/pubmed/20876285", "http://www.ncbi.nlm.nih.gov/pubmed/18596939", "http://www.ncbi.nlm.nih.gov/pubmed/21937590", "http://www.ncbi.nlm.nih.gov/pubmed/19597153", "http://www.ncbi.nlm.nih.gov/pubmed/22387281", "http://www.ncbi.nlm.nih.gov/pubmed/22550943", "http://www.ncbi.nlm.nih.gov/pubmed/22970173" ], "ideal_answer": [ "Yes. It has been demonstrated in several experimental studies that miR-21 has oncogenic potential, and is significantly dysregulated in numerous types of cancer. Therefore, miR-21 is closely related to carcinogenesis." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/P21_BYVU" ], "type": "yesno", "id": "511a4ec01159fa8212000004", "snippets": [ { "offsetInBeginSection": 1460, "offsetInEndSection": 1553, "text": "miR-21* and miR-203 were significantly dysregulated (P < 0.05) in PTC tissues with BRAFV600E.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23416953", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Expressions of miRNAs in papillary thyroid carcinoma and their associations with the BRAFV600E mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23416953", "endSection": "title" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1360, "text": "Levels of miRNA-21 (miR-21) and miR-106a in gastric cancer tissues were significantly higher compared with the levels in adjacent tissues (P = .006 and P = .001, respectively). Patients who had gastric cancer had significantly different levels of gastric juice miR-21 and miR-106a compared with patients who had benign gastric diseases (both P < .001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23335180", "endSection": "sections.0" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1591, "text": "miR-21 levels in intestinal type gastric cancer specimens were higher than that in diffuse (P = .003) or mixed (P < .001) gastric cancer types.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23335180", "endSection": "sections.0" }, { "offsetInBeginSection": 804, "offsetInEndSection": 1130, "text": "MiR-155 and miR-21 appeared significantly over-expressed in the colonic mucosa of IBD subjects without CRC, but also in neoplastic tissues of IBD patients compared to non-IBD controls (p<0.001). Importantly, in patients with IBD-CRCs, miR-155 and miR-21 over-expression extended to the distant non-neoplastic mucosa (p<0.001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288924", "endSection": "sections.0" }, { "offsetInBeginSection": 294, "offsetInEndSection": 495, "text": "Here we hypothesize that over-expression of miR-155 and miR-21, two inflammation-related miRNAs that target core MMR proteins, may constitute a pre-neoplastic event for the development of MSI IBD-CRCs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288924", "endSection": "sections.0" }, { "offsetInBeginSection": 285, "offsetInEndSection": 661, "text": "After administration, we determined the expressions of miR-21, miR-27a, miR-34a, miR-93, miR-143, miR-146a, miR-148a, miR-155, miR-196a, miR-203, miR-205, miR-221 and nuclear factor kappa-light-chain enhancer of activated B-cells-1 (Nf\u03bab1), mitogen-activated protein kinase-8 (Mapk8) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) genes in the liver of mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23239858", "endSection": "sections.0" }, { "offsetInBeginSection": 88, "offsetInEndSection": 188, "text": "Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is controlled by miR-21.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212265", "endSection": "sections.0" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1375, "text": "Consistently with PDCD4 downregulation, miR-21 was upregulated in neoplastic by comparison with nonneoplastic tissue samples.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212265", "endSection": "sections.0" }, { "offsetInBeginSection": 449, "offsetInEndSection": 632, "text": "Expression of miR-21 (p=0.027), miR-181b (p=0.002), and miR-146b (p=0.021) in tumor tissue and miR-21 (p=0.003) in noncancerous tissue were associated with patients' overall survival.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175214", "endSection": "sections.0" }, { "offsetInBeginSection": 319, "offsetInEndSection": 575, "text": "We analyzed the expression of nine miRNAs (miR-21, miR-127, miR-154, miR-224, miR-323, miR-370, miR-9*, miR-183, and miR-375) by quantitative real-time-polymerase chain reaction in 34 cases of sMTC, 6 cases of hMTC, and 2 cases of C-cell hyperplasia (CCH).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22747440", "endSection": "sections.0" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1206, "text": "MTC and CCH were both characterized by a significant overexpression of the whole set of miRNAs (the increase being 4.2-fold for miR-21, 6.7-fold for miR-127, 8.8-fold for miR-154, 6.6-fold for miR-224, 5.8-fold for miR-323, 6.1-fold for miR-370, 13-fold for miR-9*, 6.7-fold for miR-183, and 10.1 for miR-375, p<0.0001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22747440", "endSection": "sections.0" }, { "offsetInBeginSection": 304, "offsetInEndSection": 585, "text": "The most frequent changes in miRNAs in CLL cells included downregulation of miR-126, miR-572, miR-494, miR-923, miR-638, miR-130a, miR-181a and miR-181b and up-regulation of miR-29a, miR-660, miR-20a, miR-106b, miR-142-5p, miR-101, miR-30b, miR-34a, miR-let-7f, miR-21 and miR-155.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22610076", "endSection": "sections.0" }, { "offsetInBeginSection": 839, "offsetInEndSection": 1170, "text": "Results: MTC and CCH were both characterized by a significant overexpression of the whole set of miRNAs (the increase being 4.2-fold for miR-21, 6.7-fold for miR-127, 8.8-fold for miR-154, 6.6-fold for miR-224, 5.8-fold for miR-323 and 6.1-fold for miR-370, 13-fold for miR-9*, 6.7-fold for miR-183 and 10.1 for miR-375, p<0.0001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22550943", "endSection": "sections.0" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1002, "text": "We found that the onco-miRNAs miR-21 and miR-221 displayed upregulated expression while the liver-specific miR-122 was downregulated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22265967", "endSection": "sections.0" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1313, "text": "The aim of the present review was to describe the mechanisms of several known miR, summarize recent studies on oncogenic miR (e.g. miR-21, miR-106a and miR-17), tumor suppressor miR (e.g. miR-101, miR-181, miR-449, miR-486, let-7a) and controversial roles of miR (e.g. miR-107, miR-126) for gastric cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22168593", "endSection": "sections.0" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1097, "text": "MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21937590", "endSection": "sections.0" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1526, "text": "Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21937590", "endSection": "sections.0" }, { "offsetInBeginSection": 545, "offsetInEndSection": 971, "text": "Many aberrantly expressed miRNAs were related to various cancers (e.g., miR-125b, hepatocellular carcinoma; miR-21, leukemia; miR-16, chronic lymphocytic leukemia; miR-192, pituitary adenomas; miR-199a-3p, ovarian cancer; miR-34a, pancreatic cancer). Several miRNAs (e.g., miR-34a, miR-21) and proteins (e.g., TGM2, NDRG2) that play crucial roles in liver tumorigenesis were first found to be affected by MC-LR in mouse liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21882851", "endSection": "sections.0" }, { "offsetInBeginSection": 1363, "offsetInEndSection": 1482, "text": "Except for miR-21 and miR-206, the expression levels of all miRNAs significantly changed during the progression of CaP.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880514", "endSection": "sections.0" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1578, "text": "In addition, diet and carcinogen exposure modulated a number of microRNAs (miR-16, miR-19b, miR-21, miR26b, miR27b, miR-93, and miR-203) linked to canonical oncogenic signaling pathways.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21406606", "endSection": "sections.0" }, { "offsetInBeginSection": 633, "offsetInEndSection": 817, "text": "RESULTS: Elevated miR-21 (HR 2.06, 1.13-3.75), miR-17 (HR 2.00, 1.10-3.61), and miR-155 (HR 2.37, 1.27-4.42) was associated with worse cancer-specific mortality in the Maryland cohort.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21350005", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "NF-\u03baB targets miR-16 and miR-21 in gastric cancer: involvement of prostaglandin E receptors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081469", "endSection": "title" }, { "offsetInBeginSection": 377, "offsetInEndSection": 561, "text": "Expression of miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a was determined by quantitative real-time PCR in formalin-fixed paraffin-embedded tumor specimens from 639 IALT patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978195", "endSection": "sections.0" }, { "offsetInBeginSection": 634, "offsetInEndSection": 831, "text": "hese two miRNAs have previously been identified as being overexpressed in MCF-7 breast cancer cells, with miR-21 specifically implicated in down-regulating the tumor suppressor gene, tropomyosin-1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20952761", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "MicroRNA-21 is involved in ionizing radiation-promoted liver carcinogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20827319", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 817, "text": "We showed here that among several hundred miRNAs, miR-21 was the only one that increased 6 folds in high-LET IR-promoted mouse liver tumors when compared with that in the non-irradiated liver tissues. We also showed that miR-21 was up-regulated in human or mouse hepatocytes after exposure to IR, as well as in liver tissues derived from whole body irradiated mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20827319", "endSection": "sections.0" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1070, "text": "After the non-irradiated, low-LET or high-LET irradiated human hepatocytes were over-expressed with miR-21, these cells became tumorigenesis in nude mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20827319", "endSection": "sections.0" }, { "offsetInBeginSection": 765, "offsetInEndSection": 1035, "text": "METHODS: We used this combined ISH/IHC assay to study a subset of cancer-associated miRNAs, including miRNAs frequently detected at low (miR-34a and miR-126) and high (miR-21 and miR-155) levels, in a panel of breast, colorectal, lung, pancreas, and prostate carcinomas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682703", "endSection": "sections.0" }, { "offsetInBeginSection": 1915, "offsetInEndSection": 2080, "text": "The miR-15a, miR-16, miR-143, miR-155, and miR-21 were upregulated in M059K, and the modulation of these miRNAs fluctuated in M059J cells in a time-dependent manner.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20380575", "endSection": "sections.0" }, { "offsetInBeginSection": 91, "offsetInEndSection": 287, "text": "Aberrantly increased expression of miR-21 plays a significant role in lung carcinogenesis and is a potential therapeutic target in both epidermal growth factor receptor-mutant and wild-type cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20338946", "endSection": "sections.0" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1174, "text": "Additionally, high miR-21 expression was associated with significantly decreased 5 year survival in patients (hazard ratio, 1.68; 95% CI: 1.04-2.77) in a model controlled for patient age, gender and tumor stage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901002", "endSection": "sections.0" }, { "offsetInBeginSection": 751, "offsetInEndSection": 936, "text": "ESULTS: In adenocarcinoma patients, miR-21, miR-223, miR-192, and miR-194 expression was elevated, whereas miR-203 expression was reduced in cancerous compared with noncancerous tissue.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19789312", "endSection": "sections.0" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1430, "text": "Significantly, elevated miR-21 expression in noncancerous tissue of SCC patients and reduced levels of miR-375 in cancerous tissue of adenocarcinoma patients with Barrett's were strongly associated with worse prognosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19789312", "endSection": "sections.0" }, { "offsetInBeginSection": 723, "offsetInEndSection": 1071, "text": "miR-21, mir-31, miR-130a, miR-146b and miR-377 were consistently upregulated, whereas miR-1 and miR-143 were downregulated in lung tumors relative to normal lungs. In mice treated with VC and given I3C in the diet, levels of miR-21, mir-31, miR-130a, miR-146b and miR-377 were reduced relative to the level in mice treated with the carcinogen only.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748927", "endSection": "sections.0" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1474, "text": "Further studies with miR-21 indicated that phosphatase and tensin homolog, programmed cell death 4 and rich protein with Kazal motifs are potential targets for the oncogenic effect of miR-21 and the chemopreventive activity of I3C.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748927", "endSection": "sections.0" }, { "offsetInBeginSection": 144, "offsetInEndSection": 336, "text": "This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19737943", "endSection": "sections.0" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1780, "text": "CONCLUSIONS: IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19737943", "endSection": "sections.0" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1374, "text": "The most highly expressed miRNAs in gastric cancer tissues were miR-20b, miR-20a, miR-17, miR-106a, miR-18a, miR-21, miR-106b, miR-18b, miR-421, miR-340*, miR-19a and miR-658.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19175831", "endSection": "sections.0" }, { "offsetInBeginSection": 357, "offsetInEndSection": 959, "text": "Recent findings report their involvement in hair follicle morphogenesis (ablation of miRNAs from keratinocytes causes several defects, such as evagination instead of invagination), in psoriasis (skin-specific expression of miR-203 and psoriasisspecific expression of miR-146a, miR-21 and miR-125b in the skin), in autoimmune diseases affecting the skin, such as SLE and ITP, in wound healing (changes in the expression of specific miRNA at specific phases of the regeneration process), and in skin carcinogenesis (a novel miRNA signature that includes induction of miR-21, a candidate oncogenic miRNA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18853072", "endSection": "sections.0" }, { "offsetInBeginSection": 597, "offsetInEndSection": 854, "text": "RESULTS: Several microRNAs were differentially expressed in serous ovarian carcinoma compared with normal ovarian tissues, including miR-21, miR-125a, miR-125b, miR-100, miR-145, miR-16, and miR-99a, which were each differentially expressed in >16 patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18451233", "endSection": "sections.0" }, { "offsetInBeginSection": 1251, "offsetInEndSection": 1620, "text": "Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P < .001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18230780", "endSection": "sections.0" }, { "offsetInBeginSection": 235, "offsetInEndSection": 467, "text": "To test this hypothesis, we studied the pharmacologic roles of three microRNAs previously implicated in cancer biology (let-7i, mir-16, and mir-21) and also used in silico methods to test pharmacologic microRNA effects more broadly.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18187804", "endSection": "sections.0" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1554, "text": "Changing the cellular levels of let-7i, mir-16, and mir-21 affected the potencies of a number of the anticancer agents by up to 4-fold. The effect was most prominent with mir-21, with 10 of 28 cell-compound pairs showing significant shifts in growth-inhibitory activity. Varying mir-21 levels changed potencies in opposite directions depending on compound class; indicating that different mechanisms determine toxic and protective effects. In silico comparison of drug potencies with microRNA expression profiles across the entire NCI-60 panel revealed that approximately 30 microRNAs, including mir-21, show highly significant correlations with numerous anticancer agents.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18187804", "endSection": "sections.0" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1139, "text": "Conversely, expression of other miRNAs was detected at varying levels predominantly within luminal epithelial cells in normal tissue; expression of miR-21 was frequently increased, whereas that of let-7a was decreased in malignant cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18089790", "endSection": "sections.0" }, { "offsetInBeginSection": 447, "offsetInEndSection": 596, "text": "We describe a novel EMT-specific microRNA signature that includes induction of miR-21, a candidate oncogenic microRNA associated with carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17587821", "endSection": "sections.0" }, { "offsetInBeginSection": 508, "offsetInEndSection": 562, "text": "Notable was the high expression of miR-21 and miR-205.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17475218", "endSection": "sections.0" }, { "offsetInBeginSection": 172, "offsetInEndSection": 331, "text": "Recently, microRNAs (miRNAs) have emerged as key actors in carcinogenesis and we demonstrated that microRNA-21 (miR-21), oncomiR is expressed early during PDA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23481326", "endSection": "sections.0" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1571, "text": "These results indicated that miR-21 plays a role in the carcinogenesis and metastasis of O. viverrini-associated CCA by suppressing the function of PDCD4.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23417858", "endSection": "sections.0" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1171, "text": "Importantly, in patients with IBD CRCs, miR-155 and miR-21 overexpression extended to the distant non-neoplastic mucosa (P < 0.001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288924", "endSection": "sections.0" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 1578, "text": "Ectopic overexpression of miR-21 promoted Akt activation and phosphorylation of EZH2, whereas inhibiting miR-21 by transfecting the cells with anti-miR-21 inhibited Akt activation and EZH2 phosphorylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23255093", "endSection": "sections.0" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1719, "text": "PDCD4 nuclear down-regulation (which parallels miR-21 up-regulation) is involved in the molecular pathway of IBD-associated carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23224068", "endSection": "sections.0" }, { "offsetInBeginSection": 457, "offsetInEndSection": 660, "text": "The expression levels of miR-21 (p = 0.027), miR-181b (p = 0.002) and miR-146b (p = 0.021) in tumor tissue and miR-21 (p = 0.003) in noncancerous tissue were associated with overall survival of patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175214", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "OBJECTIVE: As an important oncogenic miRNA, miR-21 has been reported to play crucial roles in glioblastoma (GBM) carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22709411", "endSection": "sections.0" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1291, "text": "We further analyzed the expression of microRNA-21 (miR-21), an oncogenic noncoding RNA involved in oncogenic Ras signaling, by quantitative reverse-transcription polymerase chain reaction and in situ hybridization.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22618808", "endSection": "sections.0" }, { "offsetInBeginSection": 78, "offsetInEndSection": 193, "text": "MicroRNA-21 (miR-21) plays crucial roles in carcinogenesis and is considered as one of the most studied oncomiRNAs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430134", "endSection": "sections.0" }, { "offsetInBeginSection": 281, "offsetInEndSection": 456, "text": "Although microRNA-21 (miR-21) has been implicated in various aspects of carcinogenesis, its functions and molecular mechanisms in carcinogen-induced tumorigenesis are unclear.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22387281", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Substantial evidence indicates that microRNA-21 (miR-21) is a key oncomiR in carcinogenesis and is significantly elevated in multiple myeloma (MM).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22316494", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "MicroRNA 21 (miR-21) has been implicated in various aspects of carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22001440", "endSection": "sections.0" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1290, "text": "Conversely, pAkt and miR-21 expression was significantly up-regulated in the whole spectrum of preneoplastic/neoplastic lesions considered.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21883657", "endSection": "sections.0" }, { "offsetInBeginSection": 796, "offsetInEndSection": 971, "text": "Several miRNAs (e.g., miR-34a, miR-21) and proteins (e.g., TGM2, NDRG2) that play crucial roles in liver tumorigenesis were first found to be affected by MC-LR in mouse liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21882851", "endSection": "sections.0" }, { "offsetInBeginSection": 1354, "offsetInEndSection": 1482, "text": "RESULTS: Except for miR-21 and miR-206, the expression levels of all miRNAs significantly changed during the progression of CaP.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880514", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and various types of hematological malignancies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21646541", "endSection": "sections.0" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1377, "text": "As expected, miR-21 expression was significantly upregulated in preneoplastic/neoplastic samples, consistent with PDCD4 downregulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279518", "endSection": "sections.0" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1262, "text": "Furthermore, miR-21 levels in the primary tumours correlated with disease stage (P\u2009<\u20090.0001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21088996", "endSection": "sections.0" }, { "offsetInBeginSection": 398, "offsetInEndSection": 562, "text": "We found that miR-16 and miR-21 were upregulated upon nicotine stimulation, transfection with anti-miR-16 or anti-miR-21 significantly abrogated cell proliferation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081469", "endSection": "sections.0" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1074, "text": "MicroRNA-21 (miR-21) is a unique miRNA in that it is overexpressed in most tumour types analysed so far.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20693987", "endSection": "sections.0" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1413, "text": "Although altered expressions of miR-21 and miR-34a were manifested within cancer cells, those of miR-126 and miR-155 were predominantly confined to endothelial cells and immune cells, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682703", "endSection": "sections.0" }, { "offsetInBeginSection": 221, "offsetInEndSection": 286, "text": "However, the function of miR-21 in osteosarcoma is still unclear.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20480266", "endSection": "sections.0" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1064, "text": "In SCC patients, we found elevated miR-21 and reduced miR-375 expression levels in cancerous compared with noncancerous tissue.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19789312", "endSection": "sections.0" }, { "offsetInBeginSection": 723, "offsetInEndSection": 886, "text": "miR-21, mir-31, miR-130a, miR-146b and miR-377 were consistently upregulated, whereas miR-1 and miR-143 were downregulated in lung tumors relative to normal lungs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748927", "endSection": "sections.0" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1219, "text": "Precancerous adenomas also frequently showed miR-21 up-regulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509156", "endSection": "sections.0" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1462, "text": "Higher miR-21 expression was present in adenomas (P = .006)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18230780", "endSection": "sections.0" }, { "offsetInBeginSection": 695, "offsetInEndSection": 873, "text": "Importantly, the inflammatory ZD esophagus had a distinct microRNA signature resembling human ESCC or tongue SCC miRNAomes with miR-31 and miR-21 as the top-up-regulated species.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22689922", "endSection": "sections.0" }, { "offsetInBeginSection": 285, "offsetInEndSection": 536, "text": "Several miRNAs have been recently reported to be involved in modulation of glioma development, especially some upregulated miRNAs, such as microRNA-21 (miR-21), which has been found to function as an oncogene in cultured glioblastoma multiforme cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22528454", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "OBJECTIVE: MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only a little is known about its functional role in CRC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476768", "endSection": "sections.0" }, { "offsetInBeginSection": 854, "offsetInEndSection": 1042, "text": "Inhibition of microRNA-21 (mir\u201121) induced upregulation of Spry2 and PTEN which underscores the importance of mir-21 in Spry2-associated tumorigenesis of the colon.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22322462", "endSection": "sections.0" }, { "offsetInBeginSection": 886, "offsetInEndSection": 999, "text": "The microRNA miR-21, a known oncogenic miRNA, was found to be upregulated in papillary and clear cell carcinomas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21532496", "endSection": "sections.0" }, { "offsetInBeginSection": 112, "offsetInEndSection": 258, "text": "Since microRNA-21 (miR-21) may contribute to tumorigenesis and chemoresistance in many cancer types, we aimed to investigate its efficacy in TCCs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21468550", "endSection": "sections.0" }, { "offsetInBeginSection": 285, "offsetInEndSection": 537, "text": "Several miRNAs have been recently reported to be involved in modulation of glioma development, especially some up-regulated miRNAs, such as microRNA-21 (miR-21), which has been found to function as an oncogene in cultured glioblastoma multiforme cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20633539", "endSection": "sections.0" }, { "offsetInBeginSection": 659, "offsetInEndSection": 953, "text": "In this study, by using high-throughput microRNA profiling, we identified that two miRNAs (miR-21 and miR-148a) overexpressed in CD4+ T cells from both patients with lupus and lupus-prone MRL/lpr mice, which promote cell hypomethylation by repressing DNA methyltransferase 1 (DNMT1) expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20483747", "endSection": "sections.0" }, { "offsetInBeginSection": 108, "offsetInEndSection": 229, "text": "The microRNA-21 (miR-21) has been identified as the only miRNA overexpressed in a variety of cancers, including leukemia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20141427", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "OBJECTIVE: The contribution of overexpressed microRNA-21 and -221 (miR-21 and miR-221) to the malignant phenotype was determined by inhibiting these miRNAs using antisense oligonucleotides.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19730150", "endSection": "sections.0" }, { "offsetInBeginSection": 52, "offsetInEndSection": 185, "text": "The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19682430", "endSection": "sections.0" }, { "offsetInBeginSection": 379, "offsetInEndSection": 626, "text": "To determine the functions of these microRNAs in lymphomagenesis, we examined the effects of antisense oligonucleotides (ASOs) targeting miR-21 (ASO-21) and/or miR-155 (ASO-155) in NK-cell lymphoma lines overexpressing one or both of these miRNAs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19641183", "endSection": "sections.0" }, { "offsetInBeginSection": 343, "offsetInEndSection": 670, "text": "In this study, microRNA (miRNA) expression profiling of 28 cases of never-smoker lung cancer identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., up-regulated miR-21) and unidentified (e.g., down-regulated miR-138) in those smoker cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19597153", "endSection": "sections.0" }, { "offsetInBeginSection": 482, "offsetInEndSection": 584, "text": "The oncogenic miRNA, microRNA-21 (miR-21), was found to be upregulated in laryngeal carcinoma tissues.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19546886", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "OBJECTIVE: To better understand microRNA miR-21 function in carcinogenesis, we analyzed miR-21 expression patterns in different stages of colorectal cancer development using in situ hybridization (ISH).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509156", "endSection": "sections.0" }, { "offsetInBeginSection": 153, "offsetInEndSection": 287, "text": "Of these miRNAs, miR-21 appears to be important in tumorigenesis given its up-regulation in almost all types of human cancer examined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18507035", "endSection": "sections.0" }, { "offsetInBeginSection": 127, "offsetInEndSection": 326, "text": "The microRNA-21 gene (mir-21) has been identified as the only miRNA commonly overexpressed in solid tumors of the lung, breast, stomach, prostate, colon, brain, head and neck, esophagus and pancreas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18372920", "endSection": "sections.0" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1495, "text": "RESULTS: Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16966691", "endSection": "sections.0" }, { "offsetInBeginSection": 435, "offsetInEndSection": 848, "text": "To search for tumor-associated mutations that could affect processing and expression of mature miRNAs, a panel of 91 cancer-derived cell lines was analyzed for sequence variations in 15 miRNAs implicated in tumorigenesis by virtue of their known target transcripts (let-7 family targeting oncogenic Ras) or their localization to sites of frequent chromosomal instability (miR-143, miR-145, miR-26a-1, and miR-21).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16778182", "endSection": "sections.0" } ] }, { "body": "Which is the most prevalent form of arrhythmia worldwide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23795692", "http://www.ncbi.nlm.nih.gov/pubmed/24828991", "http://www.ncbi.nlm.nih.gov/pubmed/23259476", "http://www.ncbi.nlm.nih.gov/pubmed/23541013", "http://www.ncbi.nlm.nih.gov/pubmed/24474959", "http://www.ncbi.nlm.nih.gov/pubmed/25432121", "http://www.ncbi.nlm.nih.gov/pubmed/19888755", "http://www.ncbi.nlm.nih.gov/pubmed/15922277", "http://www.ncbi.nlm.nih.gov/pubmed/25534665", "http://www.ncbi.nlm.nih.gov/pubmed/21394037", "http://www.ncbi.nlm.nih.gov/pubmed/25546992" ], "ideal_answer": [ "Atrial fibrillation (AF) is the most common arrhythmia worldwide, and it has a significant effect on morbidity and mortality. It is a significant risk factor for stroke and peripheral embolization, and it has an effect on cardiac function. Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting up to 1-1.5% of the population." ], "exact_answer": [ "atrial fibrilation", "AF" ], "type": "factoid", "id": "54d8ea2c4b1fd0d33c000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Atrial fibrillation remains the most prevalent cardiac arrhythmia, and its incidence is increasing as the population ages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24828991", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 93, "text": "Atrial fibrillation is the most prevalent sustained arrhythmia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and has a significant impact on morbidity and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Atrial fibrillation is the most common heart rhythm disorder in the world, with major public health impact especially due to increased risk of stroke and hospitalizations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25432121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Atrial fibrillation is the most common arrhythmia affecting patients today.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24474959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Atrial fibrillation (AF) is the most common arrhythmia worldwide, and it has a significant effect on morbidity and mortality. It is a significant risk factor for stroke and peripheral embolization, and it has an effect on cardiac function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23541013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting up to 1-1.5% of the population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25546992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Atrial fibrillation is the most prevalent form of cardiac arrhythmia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19888755", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 257, "text": "Atrial fibrillation, the most prevalent arrhythmia, affects more than two million Americans annually and is associated with a twofold increase in mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15922277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Atrial fibrillation (AF) is associated with increased morbidity and is in addition the most prevalent cardiac arrhythmia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21394037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in clinical practice associated with significant morbidity and mortality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23795692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Atrial fibrillation is the most prevalent form of cardiac arrhythmia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19888755", "endSection": "abstract" } ] }, { "body": "Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23528896", "http://www.ncbi.nlm.nih.gov/pubmed/23633213", "http://www.ncbi.nlm.nih.gov/pubmed/12750454" ], "ideal_answer": [ "thyroid hormone receptor alpha1 mutations are implicated in thyroid hormone resistance syndrome" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018382", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021" ], "type": "yesno", "id": "52ecd56198d023950500002b", "snippets": [ { "offsetInBeginSection": 844, "offsetInEndSection": 1050, "text": "Mutations in human TR\u03b11 mediate RTH with features of hypothyroidism in particular tissues (e.g. skeleton, gastrointestinal tract), but are not associated with a markedly dysregulated pituitary-thyroid axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23528896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Clinical phenotype of a new type of thyroid hormone resistance caused by a mutation of the TR\u03b11 receptor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633213", "endSection": "title" } ] }, { "body": "Which agents are included in the FLAMSA chemotherapy regimen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18176613", "http://www.ncbi.nlm.nih.gov/pubmed/23728608", "http://www.ncbi.nlm.nih.gov/pubmed/21963618", "http://www.ncbi.nlm.nih.gov/pubmed/21358688", "http://www.ncbi.nlm.nih.gov/pubmed/19430496", "http://www.ncbi.nlm.nih.gov/pubmed/23652585", "http://www.ncbi.nlm.nih.gov/pubmed/22983588" ], "ideal_answer": [ "Fludarabine, cytarabine and amsacrine are included in the FLAMSA chemotherapy regimen." ], "exact_answer": [ [ "fludarabine" ], [ "cytarabine" ], [ "amsacrine" ] ], "type": "list", "id": "54e071e11388e8454a00000d", "snippets": [ { "offsetInBeginSection": 560, "offsetInEndSection": 770, "text": "After 3 days of rest, RIC was carried out, consisting of 4 Gy total body irradiation, antithymocyte globulin (ATG-Fresenius), and cyclophosphamide (fludarabine, amsacrine, and cytarabine (FLAMSA)-RIC protocol).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728608", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 402, "text": "We report a retrospective single center analysis of aplasia-inducing chemotherapy using fludarabine, cytarabine, and amsacrine (FLAMSA) followed by reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (HCT) in 62 consecutive primary refractory or relapsed AML patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652585", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1041, "text": "A sequential regimen of cytoreductive chemotherapy (fludarabine, high-dose AraC, amsacrine) followed by reduced intensity conditioning (FLAMSA-RIC), was uniformly used for conditioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22983588", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 661, "text": "Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 \u00d7 30 mg/m(2)), amsacrine (4 \u00d7 100 mg/m(2)), and Ara-C (4 \u00d7 2 g/m(2), FLAMSA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963618", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 457, "text": "The preparative regimen consisted of fludarabine, Ara-C and amsacrine (FLAMSA) chemotherapy, followed by reduced intensity conditioning (RIC) 3 days later. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358688", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 605, "text": "Fifteen patients received fludarabine 30 mg/m(2), cytarabine 2000 mg/m(2), amsacrine 100 mg/m(2) on days -10, -9, -8 and -7, anti-thymocyte globulin (ATG-Fresenius) 20 mg/kg body weight on days -6, -5 and -4 and fractionated total body irradiation 2 x 2 Gy on days -3, -2 and -1 (FLAMSA-ATG-TBI) before allogeneic hematopoietic stem cell transplantation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19430496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "The goal of this analysis was to define the role of the moderate-intensity fludarabin Ara-C amsacrin (FLAMSA)-reduced intensity conditioning (RIC) regimen for patients with high-risk AML undergoing allogeneic SCT (alloSCT) in first CR1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18176613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "The goal of this analysis was to define the role of the moderate-intensity fludarabin Ara-C amsacrin (FLAMSA)-reduced intensity conditioning (RIC) regimen for patients with high-risk AML undergoing allogeneic SCT (alloSCT) in first CR1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18176613", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 454, "text": "The preparative regimen consisted of fludarabine, Ara-C and amsacrine (FLAMSA) chemotherapy, followed by reduced intensity conditioning (RIC) 3 days later", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358688", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1039, "text": "A sequential regimen of cytoreductive chemotherapy (fludarabine, high-dose AraC, amsacrine) followed by reduced intensity conditioning (FLAMSA-RIC), was uniformly used for conditioning", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22983588", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1040, "text": "A sequential regimen of cytoreductive chemotherapy (fludarabine, high-dose AraC, amsacrine) followed by reduced intensity conditioning (FLAMSA-RIC), was uniformly used for conditioning", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22983588", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 401, "text": "We report a retrospective single center analysis of aplasia-inducing chemotherapy using fludarabine, cytarabine, and amsacrine (FLAMSA) followed by reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (HCT) in 62 consecutive primary refractory or relapsed AML patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652585", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 455, "text": "The preparative regimen consisted of fludarabine, Ara-C and amsacrine (FLAMSA) chemotherapy, followed by reduced intensity conditioning (RIC) 3 days later", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358688", "endSection": "abstract" } ] }, { "body": "Which are the subunits of the IkB protein kinase (IKK)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17977820", "http://www.ncbi.nlm.nih.gov/pubmed/19079347", "http://www.ncbi.nlm.nih.gov/pubmed/23294515", "http://www.ncbi.nlm.nih.gov/pubmed/21784860", "http://www.ncbi.nlm.nih.gov/pubmed/20300203", "http://www.ncbi.nlm.nih.gov/pubmed/19830703", "http://www.ncbi.nlm.nih.gov/pubmed/19666475", "http://www.ncbi.nlm.nih.gov/pubmed/21603248", "http://www.ncbi.nlm.nih.gov/pubmed/21314234", "http://www.ncbi.nlm.nih.gov/pubmed/22301997", "http://www.ncbi.nlm.nih.gov/pubmed/21294676", "http://www.ncbi.nlm.nih.gov/pubmed/17924664", "http://www.ncbi.nlm.nih.gov/pubmed/24266532", "http://www.ncbi.nlm.nih.gov/pubmed/22627374", "http://www.ncbi.nlm.nih.gov/pubmed/24242761" ], "ideal_answer": [ "Proinflammatory NF-kappaB activation requires the IkappaB (inhibitor of NF-kappaB) kinase (IKK) complex that contains two catalytic subunits named IKKalpha and IKKbeta and a regulatory subunit named NF-kappaB essential modulator (NEMO).Additional components may exist, transiently or permanently, but their characterization is still unsure.", "The IKK kinase complex is the core element of the NF-kappaB cascade. It is essentially made of two kinases (IKKalpha and IKKbeta) and a regulatory subunit, NEMO (NF-kB Essential Modulator)/IKKgamma. Additional components may exist, transiently or permanently, but their characterization is still unsure.", " The IKK protein complex is comprised of IKK\u03b1, IKK\u03b2 and NEMO subunits, with IKK\u03b2 thought to play the dominant role in modulating NF-\u03baB activity. The IkappaB-Kinase (IKK) complex is a multisubunit protein complex crucial for signal-induced phosphorylation of the IkappaB proteins and thus controls the activity of the transcription factor NF-kappaB. Besides the two kinases IKKalpha and IKKbeta, the IKK complex contains NEMO/IKKgamma, an additional subunit with regulatory and adaptor functions. " ], "exact_answer": [ [ "IKKalpha", "IKK\u03b1", "IKK1" ], [ "IKKbeta", "IKK\u03b2", "IKK2" ], [ "IKKgamma", "IKK\u03b3", "NEMO" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008384" ], "type": "list", "id": "5506e2ff8e1671127b00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "NEMO (NF-\u03baB essential modulator) associates with catalytic subunits IKK\u03b1 and IKK\u03b2 to form the I\u03baB kinase (IKK) complex and is a key regulator of NF-\u03baB pathway signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24266532", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 510, "text": "All known NF-\u03baB activators converge on the IkappaB kinase (IKK) complex to activate the canonical and non-canonical NF-\u03baB pathways. The IKK complex contains two catalytic subunits (IKK\u03b1 and IKK\u03b2) and a regulatory subunit NEMO/IKK\u03b3 that regulates the canonical NF-\u03baB pathway, whereas IKK\u03b1 regulates the non-canonical pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24242761", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 555, "text": " The IKK protein complex is comprised of IKK\u03b1, IKK\u03b2 and NEMO subunits, with IKK\u03b2 thought to play the dominant role in modulating NF-\u03baB activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23294515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "The I\u03baB kinase (IKK) complex plays a crucial role in the activation of the transcription factor NF-\u03baB by phosphorylating an inhibitory molecule I\u03baB\u03b1. Recently, we showed that IKK2 (also called IKK\u03b2), a catalytic subunit of the IKK complex, induces immunoglobulin E-mediated degranulation in mast cells by phosphorylating SNAP-23, the target-membrane soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor (SNARE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627374", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 474, "text": "The depletion of any of the three subunits of the inhibitor of NF\u03baB (I\u03baB) kinase (IKK\u03b1, IKK\u03b2, IKK\u03b3/NEMO), each of which is essential for the canonical NF\u03baB activation pathway, limits autophagy induction by physiological or pharmacological triggers, while constitutive active IKK subunits suffice to stimulate autophagy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22301997", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 505, "text": "NF-\u03baB activation is tightly regulated by the I\u03baB kinase (IKK) complex, which is composed of two catalytic subunits IKK\u03b1 and IKK\u03b2, and a regulatory subunit IKK\u03b3/NEMO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21784860", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 583, "text": "Activation of the classical NF-\u03baB pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKK\u03b1, IKK\u03b2, and IKK\u03b3 subunits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21603248", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 193, "text": "NF-kB is a key regulator of inflammation and immunity in cancer development. The IkB kinase (IKK) is a multisubunit complex containing catalytic subunits termed IKK-\u03b1, -\u03b2 and -\u03b3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21314234", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 369, "text": "Activation of NF-\u03baB involves the I\u03baB kinase (IKK)-complex composed of two catalytic subunits, IKK\u03b1 and IKK\u03b2, and a regulatory scaffold protein, IKK\u03b3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21294676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The IKK kinase complex is the core element of the NF-kappaB cascade. It is essentially made of two kinases (IKKalpha and IKKbeta) and a regulatory subunit, NEMO/IKKgamma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20300203", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 275, "text": "Additional components may exist, transiently or permanently, but their characterization is still unsure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20300203", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 363, "text": "Activation of NF-kappaB subunits is regulated by the upstream IkappaB kinase (IKK) complex which contains IKKalpha, IKKbeta, and IKKgamma; the latter also known as NF-kappaB essential modulator (NEMO).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Proinflammatory NF-kappaB activation requires the IkappaB (inhibitor of NF-kappaB) kinase (IKK) complex that contains two catalytic subunits named IKKalpha and IKKbeta and a regulatory subunit named NF-kappaB essential modulator (NEMO).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666475", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 463, "text": "Inhibition of NF-kappaB by suppressing the canonical NF-kappaB activation pathway, for instance by knockdown of the three subunits of the inhibitor of NF-kappaB (I kappaB) kinase (IKK) complex (IKK1, IKK2 and NEMO) triggers apoptosis in such cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19079347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "The IkappaB-Kinase (IKK) complex is a multisubunit protein complex crucial for signal-induced phosphorylation of the IkappaB proteins and thus controls the activity of the transcription factor NF-kappaB. Besides the two kinases IKKalpha and IKKbeta, the IKK complex contains NEMO/IKKgamma, an additional subunit with regulatory and adaptor functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17977820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Activation of a large multisubunit protein kinase, called the inhibitor kappaB kinase (IKK) complex, is central to the induction of the family of transcription factors nuclear factor kappaB. IKK is comprised of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory IKKgamma subunit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17924664", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 177, "text": "The IkB kinase (IKK) is a multisubunit complex containing catalytic subunits termed IKK-\u03b1, -\u03b2 and -\u03b3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21314234", "endSection": "abstract" } ] }, { "body": "Is PLK2 involved in alpha-synuclein phosphorylation in Parkinson disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "http://www.ncbi.nlm.nih.gov/pubmed/21050448", "http://www.ncbi.nlm.nih.gov/pubmed/19004816" ], "ideal_answer": [ "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assayThese results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.", "Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances \u03b1-synuclein autophagic degradation in a kinase activity-dependent manner. These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.", "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system " ], "exact_answer": "yes", "type": "yesno", "id": "551910fa622b19434500000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "An increase in \u03b1-synuclein levels due to gene duplications/triplications or impaired degradation is sufficient to trigger its aggregation and cause familial Parkinson disease ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 540, "text": "Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances \u03b1-synuclein autophagic degradation in a kinase activity-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Polo-like kinase 2 regulates selective autophagic \u03b1-synuclein clearance and suppresses its toxicity in vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "endSection": "title" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1219, "text": "Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of \u03b1-synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983262", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 845, "text": " \u03b1-Synuclein increased PLK2 levels and GSK-3\u03b2 activity and increased the levels of phosphorylated \u03b1-Synuclein and Tau", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21050448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of alpha-synuclein phosphorylated at Ser-129 (p-Ser-129)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 477, "text": "Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 566, "text": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 975, "text": "These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19004816", "endSection": "abstract" } ] }, { "body": "Which glands are subject to attack by lymphocytes in Sjogren's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16221495", "http://www.ncbi.nlm.nih.gov/pubmed/21777618", "http://www.ncbi.nlm.nih.gov/pubmed/11439159", "http://www.ncbi.nlm.nih.gov/pubmed/20408860", "http://www.ncbi.nlm.nih.gov/pubmed/16761498", "http://www.ncbi.nlm.nih.gov/pubmed/17472721", "http://www.ncbi.nlm.nih.gov/pubmed/17823290", "http://www.ncbi.nlm.nih.gov/pubmed/11464341", "http://www.ncbi.nlm.nih.gov/pubmed/17127420" ], "ideal_answer": [ "Sj\u00f6gren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands." ], "exact_answer": [ "The lacrimal and/or salivary glands" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012469", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012859", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005088", "http://www.disease-ontology.org/api/metadata/DOID:12894", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046649", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007765" ], "type": "factoid", "id": "53189b05b166e2b80600001e", "snippets": [ { "offsetInBeginSection": 280, "offsetInEndSection": 490, "text": "In Sj\u00f6gren's syndrome the autoimmune response is directed against the exocrine glands, which, as histopathological hallmark of the disease, display persistent and progressive focal mononuclear cell infiltrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21777618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Sj\u00f6gren's syndrome (SS) is an autoimmune disease characterized by clonal B cell attack of the exocrine glands and dysregulated expression of B cell-activating factor (BAFF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20408860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Sj\u00f6gren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17823290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Sj\u00f6gren's syndrome is an autoimmune disease in which immune cells chronically attack the lachrymal and salivary glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17472721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Sj\u00f6gren's syndrome (SjS) is a systemic autoimmune disease in which an immunological attack against the salivary and lacrimal glands results, respectively, in severe dry mouth and dry eye diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17127420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune disease affecting epithelial tissues. Exocrine glands are the primary target and their functional impairment comes as a result of immune attack of epithelial cells of the affected organs (autoimmune epithelitis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16761498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Sj\u00f6gren's syndrome (SjS) is a human autoimmune disease characterized by the loss of exocrine function as a result of a chronic immune attack directed primarily against the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16221495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 391, "text": "The purpose of this qualitative research was to explore the lived experiences of women with Sjogren's Syndrome (SS), a chronic autoimmune syndrome in which invading lymphocytes attack moisture-producing glands of the body. This syndrome, affecting 4 million Americans, involves extreme dryness of the eyes and mouth and other systemic complications such as fatigue and muscle and joint pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11464341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "NOD mice manifest many features of autoimmune exocrinopathy (Sj\u00f6gren's syndrome), a disease generally characterized by a chronic, progressive immunological attack against the exocrine tissues of the salivary and lacrimal glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11439159", "endSection": "abstract" } ] }, { "body": "Describe Malgaigne fracture.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24502106", "http://www.ncbi.nlm.nih.gov/pubmed/1465304", "http://www.ncbi.nlm.nih.gov/pubmed/3111770", "http://www.ncbi.nlm.nih.gov/pubmed/11775195", "http://www.ncbi.nlm.nih.gov/pubmed/9269112", "http://www.ncbi.nlm.nih.gov/pubmed/1498111", "http://www.ncbi.nlm.nih.gov/pubmed/7876010", "http://www.ncbi.nlm.nih.gov/pubmed/1475128", "http://www.ncbi.nlm.nih.gov/pubmed/7431445", "http://www.ncbi.nlm.nih.gov/pubmed/26046617", "http://www.ncbi.nlm.nih.gov/pubmed/7204439", "http://www.ncbi.nlm.nih.gov/pubmed/2766606", "http://www.ncbi.nlm.nih.gov/pubmed/15195043", "http://www.ncbi.nlm.nih.gov/pubmed/3230497", "http://www.ncbi.nlm.nih.gov/pubmed/1942182", "http://www.ncbi.nlm.nih.gov/pubmed/25135027", "http://www.ncbi.nlm.nih.gov/pubmed/3967429", "http://www.ncbi.nlm.nih.gov/pubmed/7555349", "http://www.ncbi.nlm.nih.gov/pubmed/10894080", "http://www.ncbi.nlm.nih.gov/pubmed/8769442", "http://www.ncbi.nlm.nih.gov/pubmed/1403261" ], "ideal_answer": [ "Bilateral pubic rami fractures are characteristic to Malgaigne fractures. Patients with Malgaigne fractures are particularly prone to additional injuries." ], "type": "summary", "id": "56bce63cd36b5da37800000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Fractures of the transverse processes in the lumbar vertebrae occur as the result of major forces such as direct blunt trauma, violent lateral flexion-extension forces, avulsion of the psoas muscle, or Malgaigne fractures of the pelvis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26046617", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 758, "text": "The anteroposterior radiographic view revealed ununited fractures at the left superior and inferior pubic ramus, noted as a type I Malgaigne fracture. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15195043", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 640, "text": "Posterior urethral injuries occur more commonly with vertically applied forces, which typically create Malgaigne-type fractures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11775195", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1707, "text": "Patients with bilateral pubic rami fractures or Malgaigne fractures were particularly prone to additional injuries; therefore, abdominal CT examinations are recommended in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10894080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Pelvic fractures, especially those of a Malgaigne type, frequently occur in patients who are polytraumatized. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8769442", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 343, "text": "The authours report the case of a 27-year-old man who had suffered a severe polytrauma with blunt thoracic injury, fracture of the lumbar spine, Malgaigne-type fracture of the pelvis and fracture of the femoral shaft on the right side, 10 years before.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7876010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The paper deals with the displacement of the uterus observed during management of Malgaigne type pelvic fracture in a 33 years old female. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7555349", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 668, "text": "This problem was first described by Malgaigne in 1857 in his classic article on double vertical fractures of the pelvis, in which he described a 34-year-old woman with a pelvic fracture who subsequently died during childbirth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1403261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Eleven cases of sacroiliac dislocation and/or fracture (Malgaigne pattern) were successfully reduced and stabilized using two threaded compression rods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2766606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "We compared the mechanical performance of the Orthofix pelvic external fixator with that of the Pittsburgh triangular frame (PTF) on eight fresh-frozen cadaver pelves with experimentally created Malgaigne (double-vertical) fracture/dislocations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3230497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "A 48-year-old woman developed symptomatic superior and inferior pubic rami fractures with a concomitant subluxation of the ipsilateral sacroiliac joint three years after pelvic irradiation for a gynecologic malignancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3111770", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 411, "text": "Twenty-six of the thirty-two cadavera that were examined radiographically and dissected had a double break in the pelvic ring (Malgaigne pattern).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7204439", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 333, "text": " Initial hypotension, Malgaigne and bilateral pubic rami fractures, and blood requirements exceeding 2,000 cc were suggestive of abdominal trauma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7431445", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 341, "text": " Malgaigne-type fractures with sacroiliac disruptions were created in four cadaver pelvises. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3967429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The authors report 7 cases involving the surgical treatment of unstable pelvic ring fractures (Malgaigne type) using two compression bars, as described by Tile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9269112", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 267, "text": "Malgaigne fracture is referred to pelvic ring disruption at two sites, and is often treated surgically for its instability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24502106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Sacral fractures are generally accompanied by pelvic ring fractures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25135027", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 374, "text": "Malgaigne fracture is referred to pelvic ring disruption at two sites, and is often treated surgically for its instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24502106", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 667, "text": "This problem was first described by Malgaigne in 1857 in his classic article on double vertical fractures of the pelvis, in which he described a 34-year-old woman with a pelvic fracture who subsequently died during childbirth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1403261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The authors report 7 cases involving the surgical treatment of unstable pelvic ring fractures (Malgaigne type) using two compression bars, as described by Tile", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9269112", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 669, "text": "Another less frequently reported complication of pelvic fractures is the potential association with pregnancy and subsequent childbirth. This problem was first described by Malgaigne in 1857 in his classic article on double vertical fractures of the pelvis, in which he described a 34-year-old woman with a pelvic fracture who subsequently died during childbirth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1403261", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 880, "text": "This problem was first described by Malgaigne in 1857 in his classic article on double vertical fractures of the pelvis, in which he described a 34-year-old woman with a pelvic fracture who subsequently died during childbirth. A review of the literature reveals numerous articles addressing potential problems with parturition subsequent to a pelvic fracture and several articles dealing with pelvic fractures occurring during pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1403261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The authors report 7 cases involving the surgical treatment of unstable pelvic ring fractures (Malgaigne type) using two compression bars, as described by Tile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9269112", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 669, "text": "This problem was first described by Malgaigne in 1857 in his classic article on double vertical fractures of the pelvis, in which he described a 34-year-old woman with a pelvic fracture who subsequently died during childbirth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1403261", "endSection": "abstract" } ] }, { "body": "Name five popular computer programs used to identify genes in genomic sequences", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12023806", "http://www.ncbi.nlm.nih.gov/pubmed/15691859", "http://www.ncbi.nlm.nih.gov/pubmed/9253604", "http://www.ncbi.nlm.nih.gov/pubmed/16314312", "http://www.ncbi.nlm.nih.gov/pubmed/11337477", "http://www.ncbi.nlm.nih.gov/pubmed/14965344", "http://www.ncbi.nlm.nih.gov/pubmed/11673234", "http://www.ncbi.nlm.nih.gov/pubmed/10779488", "http://www.ncbi.nlm.nih.gov/pubmed/12538242", "http://www.ncbi.nlm.nih.gov/pubmed/16925843", "http://www.ncbi.nlm.nih.gov/pubmed/19099578", "http://www.ncbi.nlm.nih.gov/pubmed/9789092", "http://www.ncbi.nlm.nih.gov/pubmed/16925833", "http://www.ncbi.nlm.nih.gov/pubmed/16925832", "http://www.ncbi.nlm.nih.gov/pubmed/15613242", "http://www.ncbi.nlm.nih.gov/pubmed/12176826", "http://www.ncbi.nlm.nih.gov/pubmed/15924626", "http://www.ncbi.nlm.nih.gov/pubmed/17332020", "http://www.ncbi.nlm.nih.gov/pubmed/11738707", "http://www.ncbi.nlm.nih.gov/pubmed/19329068", "http://www.ncbi.nlm.nih.gov/pubmed/21901741", "http://www.ncbi.nlm.nih.gov/pubmed/15593401", "http://www.ncbi.nlm.nih.gov/pubmed/21901742", "http://www.ncbi.nlm.nih.gov/pubmed/14764563", "http://www.ncbi.nlm.nih.gov/pubmed/15961499", "http://www.ncbi.nlm.nih.gov/pubmed/19564452" ], "ideal_answer": [ "Any five from the following not exhaustive list: AUGUSTUS, MGENE, CRAIG, Agene, EUGENE, Fgenesh++C, Fgenesh++, Fgenesh, GeneID, GeneMark.hmm, GENOMIX, GESECA, GLEAN, GlimmerHMM, Gramene,JIGSAW, MAKER, ,MGENE, N-SCAN, SGP2, SNAP, ExonHunter, Evigan, Genescan, HMMGene, MZEF, Genie, Twinscan, SLAM, GRAIL." ], "exact_answer": [ [ "Genscan" ], [ "Glimmer" ], [ "Fgenesh" ], [ "Augustus" ], [ "GeneID" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019542", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015397" ], "type": "list", "id": "51716a438ed59a060a00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "This unit describes how to use the gene-finding programs GeneMark.hmm-E and GeneMark-ES for finding protein-coding genes in the genomic DNA of eukaryotic organisms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21901742", "endSection": "sections.0" }, { "offsetInBeginSection": 348, "offsetInEndSection": 451, "text": "YACOP parses and combines the output of the three gene-predicting systems Criticia, Glimmer and ZCURVE.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14965344", "endSection": "sections.0" }, { "offsetInBeginSection": 379, "offsetInEndSection": 594, "text": "In this paper we have explored the benefits of combining predictions from already existing gene prediction programs. We have introduced three novel methods for combining predictions from programs Genscan and HMMgene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12176826", "endSection": "sections.0" }, { "offsetInBeginSection": 740, "offsetInEndSection": 968, "text": "We describe the data sets on which the experiments were performed, the approaches employed by the five algorithms: GenScan, HMMGene, GeneMark, Pombe and FFG, the methodology of our evaluation, and the results of the experiments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673234", "endSection": "sections.0" }, { "offsetInBeginSection": 164, "offsetInEndSection": 279, "text": "Phat is based on a generalized hidden Markov model (GHMM) similar to the models used in GENSCAN, Genie and HMMgene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11738707", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "We present an independent comparative analysis of seven recently developed gene-finding programs: FGENES, GeneMark.hmm, Genie, Genescan, HMMgene, Morgan, and MZEF.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11337477", "endSection": "sections.0" }, { "offsetInBeginSection": 176, "offsetInEndSection": 378, "text": "We have explored the effectiveness when the results of several gene-finding programs were re-analyzed and combined. We studied several methods with four programs (FEXH, GeneParser3, GEN-SCAN and GRAIL2)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9789092", "endSection": "sections.0" }, { "offsetInBeginSection": 625, "offsetInEndSection": 690, "text": "FGENES; Gene-Mark.hmm; Genie; Genescan; HMMgene; Morgan and MZEF,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12023806", "endSection": "sections.0" } ] }, { "body": "Which are the major transcription factors regulating glycolysis in mammals?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21810481", "http://www.ncbi.nlm.nih.gov/pubmed/20141841", "http://www.ncbi.nlm.nih.gov/pubmed/21625432", "http://www.ncbi.nlm.nih.gov/pubmed/18391940", "http://www.ncbi.nlm.nih.gov/pubmed/18606808", "http://www.ncbi.nlm.nih.gov/pubmed/21042593", "http://www.ncbi.nlm.nih.gov/pubmed/22891351", "http://www.ncbi.nlm.nih.gov/pubmed/15664996", "http://www.ncbi.nlm.nih.gov/pubmed/16627239", "http://www.ncbi.nlm.nih.gov/pubmed/15838239", "http://www.ncbi.nlm.nih.gov/pubmed/9371825", "http://www.ncbi.nlm.nih.gov/pubmed/10823814", "http://www.ncbi.nlm.nih.gov/pubmed/17442734", "http://www.ncbi.nlm.nih.gov/pubmed/23388203", "http://www.ncbi.nlm.nih.gov/pubmed/12054621", "http://www.ncbi.nlm.nih.gov/pubmed/21673794", "http://www.ncbi.nlm.nih.gov/pubmed/19219035", "http://www.ncbi.nlm.nih.gov/pubmed/12200433", "http://www.ncbi.nlm.nih.gov/pubmed/16374431", "http://www.ncbi.nlm.nih.gov/pubmed/22886605", "http://www.ncbi.nlm.nih.gov/pubmed/19861459", "http://www.ncbi.nlm.nih.gov/pubmed/21084727", "http://www.ncbi.nlm.nih.gov/pubmed/21968997", "http://www.ncbi.nlm.nih.gov/pubmed/7649406", "http://www.ncbi.nlm.nih.gov/pubmed/19056893" ], "ideal_answer": [ "The main positive transcriptional regulator of Glycolysis in mammals is HIF1-alpha (Hypoxia Inducible Factor 1a). HIF1-alpha is upregulated by the oncogenes c-Myc and Src, which therefore also positively regulate glycolysis. Several reports have linked HIF-1\u03b1 induction with STAT3 activation. SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha. NF-\u03baB also stimulates glycolysis through the inhibition of PDK4 expression. Loss of the widely expressed transcription factor Oct1 induces a coordinated metabolic shift: mitochondrial activity and amino acid oxidation are increased, while glucose metabolism is reduced. HNF4alpha is critical for regulating glucose transport and glycolysis and in doing so is crucial for maintaining glucose homeostasis." ], "exact_answer": [ [ "HIF1-alpha" ], [ "c-Myc" ], [ "Src" ], [ "STAT3" ], [ "SIRT6" ], [ "NF-\u03baB" ], [ "Oct1" ], [ "HNF4-alpha" ], [ "PVHL" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006019" ], "type": "list", "id": "514168ab23fec9037500000a", "snippets": [ { "offsetInBeginSection": 35, "offsetInEndSection": 67, "text": "myc regulates hepatic glycolysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7649406", "endSection": "title" }, { "offsetInBeginSection": 1984, "offsetInEndSection": 2186, "text": "increase in c-Myc protein was able to induce liver glucose utilization and accumulation, and suggested that c-Myc transcription factor is involved in the control in vivo of liver carbohydrate metabolism", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7649406", "endSection": "sections.0" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1572, "text": "STAT3 is a negative regulator of aerobic glycolysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22891351", "endSection": "sections.0" }, { "offsetInBeginSection": 608, "offsetInEndSection": 702, "text": "HIF1 alpha-mediated switches in the energy production of tumor cells from OXPHOS to glycolysis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22886605", "endSection": "sections.0" }, { "offsetInBeginSection": 453, "offsetInEndSection": 726, "text": "NF-\u03baB organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-\u03baB inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21968997", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), which is a transcription factor that enhances glycolysis in cells in response to hypoxia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21810481", "endSection": "sections.0" }, { "offsetInBeginSection": 450, "offsetInEndSection": 581, "text": "SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha, a critical regulator of nutrient stress responses", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20141841", "endSection": "sections.0" }, { "offsetInBeginSection": 612, "offsetInEndSection": 777, "text": "SIRT6-deficient cells exhibit increased Hif1alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20141841", "endSection": "sections.0" }, { "offsetInBeginSection": 449, "offsetInEndSection": 579, "text": "c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19861459", "endSection": "sections.0" }, { "offsetInBeginSection": 870, "offsetInEndSection": 982, "text": "Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19861459", "endSection": "sections.0" }, { "offsetInBeginSection": 259, "offsetInEndSection": 452, "text": "loss of the widely expressed transcription factor Oct1 induces a coordinated metabolic shift: mitochondrial activity and amino acid oxidation are increased, while glucose metabolism is reduced.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19219035", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "PVHL is a regulator of glucose metabolism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19056893", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Carbohydrate response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in the glucose-mediated induction of gene products involved in hepatic glycolysis and lipogenesis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606808", "endSection": "sections.0" }, { "offsetInBeginSection": 375, "offsetInEndSection": 494, "text": "Activation of NF-kappaB, by loss of p53, caused an increase in the rate of aerobic glycolysis and upregulation of Glut3", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18391940", "endSection": "sections.0" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1063, "text": "p53 restricts activation of the IKK-NF-kappaB pathway through suppression of glycolysis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18391940", "endSection": "sections.0" }, { "offsetInBeginSection": 155, "offsetInEndSection": 287, "text": "cells express hypoxia-inducible factor (HIF)-1alpha, a transcription factor that responds to oxygen tension and regulates glycolysis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17442734", "endSection": "sections.0" }, { "offsetInBeginSection": 590, "offsetInEndSection": 769, "text": "The HIF-1 dependent genic products are involved in tumoral angiogenesis, in the metabolic switch to anaerobic glycolysis and in prosurvival, proliferative and apoptotic mechanisms", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16627239", "endSection": "sections.0" }, { "offsetInBeginSection": 216, "offsetInEndSection": 353, "text": "he hypoxia-inducible transcription factor (HIF) regulates the expression of genes involved in angiogenesis, erythropoiesis and glycolysis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16374431", "endSection": "sections.0" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1558, "text": "hypoxia-inducible factor-1, which activates a gene program associated with angiogenesis, glycolysis, and adaptation to pH", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15838239", "endSection": "sections.0" }, { "offsetInBeginSection": 404, "offsetInEndSection": 551, "text": "ChREBP (carbohydrate response element-binding protein) was recently identified as a candidate transcription factor in the glucose-signaling pathway", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15664996", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Hypoxia-inducible factor (HIF)-1 is a master transcription factor, which up-regulates glycolysis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200433", "endSection": "sections.0" }, { "offsetInBeginSection": 411, "offsetInEndSection": 528, "text": "(Src) express HIF-1alpha protein under normoxia, which results in the expression of multiple HIF-1alpha target genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200433", "endSection": "sections.0" }, { "offsetInBeginSection": 397, "offsetInEndSection": 628, "text": "HIF-1 alpha can then translocate to the nucleus and facilitate transcription of numerous target genes, the majority of which are involved in glycolysis and angiogenesis via heterodimerisation with the beta subunit (HIF-1 beta/ARNT)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12054621", "endSection": "sections.0" }, { "offsetInBeginSection": 155, "offsetInEndSection": 393, "text": "We previously observed that the c-Myc oncogenic transcription factor regulates lactate dehydrogenase A and induces lactate overproduction. We, therefore, sought to determine whether c-Myc controls other genes regulating glucose metabolism", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10823814", "endSection": "sections.0" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1039, "text": "overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10823814", "endSection": "sections.0" }, { "offsetInBeginSection": 1837, "offsetInEndSection": 1969, "text": "HNF4alpha is critical for regulating glucose transport and glycolysis and in doing so is crucial for maintaining glucose homeostasis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9371825", "endSection": "sections.0" } ] }, { "body": "Mutations in which gene determine response to both erlotinib and gefitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21430269", "http://www.ncbi.nlm.nih.gov/pubmed/22263058", "http://www.ncbi.nlm.nih.gov/pubmed/22738915", "http://www.ncbi.nlm.nih.gov/pubmed/23332287", "http://www.ncbi.nlm.nih.gov/pubmed/18799900", "http://www.ncbi.nlm.nih.gov/pubmed/19063875", "http://www.ncbi.nlm.nih.gov/pubmed/21777765", "http://www.ncbi.nlm.nih.gov/pubmed/19808904", "http://www.ncbi.nlm.nih.gov/pubmed/17575237", "http://www.ncbi.nlm.nih.gov/pubmed/17145836", "http://www.ncbi.nlm.nih.gov/pubmed/18997733", "http://www.ncbi.nlm.nih.gov/pubmed/20647703", "http://www.ncbi.nlm.nih.gov/pubmed/20705455", "http://www.ncbi.nlm.nih.gov/pubmed/15737014", "http://www.ncbi.nlm.nih.gov/pubmed/16199108", "http://www.ncbi.nlm.nih.gov/pubmed/16730855", "http://www.ncbi.nlm.nih.gov/pubmed/16009451", "http://www.ncbi.nlm.nih.gov/pubmed/22806307", "http://www.ncbi.nlm.nih.gov/pubmed/23507588", "http://www.ncbi.nlm.nih.gov/pubmed/16049312", "http://www.ncbi.nlm.nih.gov/pubmed/22920167", "http://www.ncbi.nlm.nih.gov/pubmed/20948254", "http://www.ncbi.nlm.nih.gov/pubmed/20512075", "http://www.ncbi.nlm.nih.gov/pubmed/18726117", "http://www.ncbi.nlm.nih.gov/pubmed/20007486", "http://www.ncbi.nlm.nih.gov/pubmed/21904575", "http://www.ncbi.nlm.nih.gov/pubmed/16705038", "http://www.ncbi.nlm.nih.gov/pubmed/15329413" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7647895", "o": "Gene Mutation" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0596611", "o": "http://linkedlifedata.com/resource/umls/label/A7850263" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7850263", "o": "Gene Mutation" } ], "ideal_answer": [ "Patients who carry somatic activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene, respond well to erlotinib and gefitinib." ], "exact_answer": [ "epidermal growth factor receptor (EGFR) gene" ], "concepts": [ "http://www.biosemantics.org/jochem#4274201", "http://www.biosemantics.org/jochem#4241662", "http://www.biosemantics.org/jochem#4241661" ], "type": "factoid", "id": "51542e44d24251bc05000081", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Mutations in the epidermal growth factor receptor gene (EGFR) are frequently observed in non-small-cell lung cancer (NSCLC),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332287", "endSection": "sections.0" }, { "offsetInBeginSection": 223, "offsetInEndSection": 445, "text": "EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have transformed therapy for patients with EGFR-mutant NSCLC and have proved superior to chemotherapy as first-line treatment for this patient group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332287", "endSection": "sections.0" }, { "offsetInBeginSection": 53, "offsetInEndSection": 361, "text": "Adenocarcinomas, the most common histologic subtype of non-small cell lung cancer (NSCLC), are frequently associated with activating mutations in the epidermal growth factor receptor (EGFR) gene. Although these patients often respond clinically to the EGFR tyrosine kinase inhibitors erlotinib and gefitinib,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22738915", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are promising therapies for patients with advanced non-small-cell lung cancer (NSCLC). Patients with somatic activating mutations in the EGFR gene have dramatic response initially, but would eventually develop resistance to these TKIs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22263058", "endSection": "sections.0" }, { "offsetInBeginSection": 242, "offsetInEndSection": 546, "text": "NSCLCs with EGFR mutations (exon 19 deletions or the exon 21 L858R) attain responses to EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, with improved response rate (RR), progression-free survival (PFS) and in some reports overall survival (OS) when compared with EGFR wildtype (WT) cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21904575", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Patients presenting with non-small cell lung cancer (NSCLC) and active EGFR mutation have a high response rate (60-70%) to EGFR tyrosine kinase inhibitors (TKI) with little immediate progression (primary resistance).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21777765", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitors, but drug resistance invariably emerges.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21430269", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "EGFR-TKI yields a long survival period in cases of non-small cell lung cancer (NSCLC), especially those with EGFR gene mutations,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20948254", "endSection": "sections.0" }, { "offsetInBeginSection": 582, "offsetInEndSection": 706, "text": "Efficacy of erlotinib was recognized in the cases in which disease control was obtained by initial treatment with gefitinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20948254", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 205, "text": "Patients with lung adenocarcinoma who carry epidermal growth factor receptor (EGFR) gene mutations respond remarkably well to EGFR tyrosine kinase inhibitor (EGFR-TKI), gefitinib, or erlotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20705455", "endSection": "sections.0" }, { "offsetInBeginSection": 24, "offsetInEndSection": 188, "text": "lung adenocarcinomas with epidermal growth factor receptor (EGFR) mutations respond to treatment with the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib;", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20007486", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) seems almost inevitable, even in patients with lung cancer that initially respond well to EGFR-TKIs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808904", "endSection": "sections.0" }, { "offsetInBeginSection": 425, "offsetInEndSection": 823, "text": "Gefitinib- or erlotinib-resistant sublines were established by exposing the parental PC-9 cell line to chronic, repeated treatments with these drugs. These resistant sublines showed more than 100-fold more resistance to gefitinib and erlotinib and acquired cross-resistance to other EGFR-TKIs. The T790M EGFR mutation was found by pyrosequencing, and this seemed to be the cause of drug resistance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808904", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Patients with advanced pulmonary adenocarcinoma exhibiting overexpression or mutation of epidermal growth factor receptor tend to respond better to targeted therapy with tyrosine kinase inhibitors such as gefitinib and erlotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18997733", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "Mutations of the epidermal growth factor receptor (EGFR) gene have been reported in non-small-cell lung cancer (NSCLC), especially in patients with adenocarcinoma and never smokers. Some common somatic mutations in EGFR, including deletion mutations in exon 19 and leucine-to-arginine substitution at amino acid position 858 (L858R) in exon 21, have been examined for their ability to predict sensitivity to gefitinib or erlotinib, which are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16730855", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Somatic mutations in exons encoding the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are found in human lung adenocarcinomas and are associated with sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16705038", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in lung adenocarcinomas that respond to the EGFR inhibitors gefitinib and erlotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16049312", "endSection": "sections.0" }, { "offsetInBeginSection": 325, "offsetInEndSection": 523, "text": "Epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)(such as gefitinib or erlotinib)treatment of lung cancer harboring EGFR gene mutation is one of the prototypes of such therapies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23507588", "endSection": "sections.0" }, { "offsetInBeginSection": 380, "offsetInEndSection": 630, "text": "patients with NSCLC and CNS metastases with epidermal growth factor receptor gene mutations who received CSF examinations during epidermal growth factor receptor-tyrosine kinase inhibitors treatment (250 mg daily gefitinib or 150 mg daily erlotinib).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22806307", "endSection": "sections.0" }, { "offsetInBeginSection": 491, "offsetInEndSection": 707, "text": "The evidence of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) such as gefitinib and erlotinib was first confirmed as the second-line treatment for non-selective patients with advanced NSCLC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20647703", "endSection": "sections.0" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1402, "text": "patients with EGFR-mutated advanced NSCLC, the first-line treatment with gefitinib had achieved a significant prolongation of progression-free survival compared with standard platinum doublet chemotherapy in a few phase III trials, and became a new standard of care. Gefitinib is highly effective for patients with advanced NSCLC with EGFR mutation even if their performance status is poor, although one should always pay careful attention to fatal interstitial lung disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20647703", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 187, "text": "The tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are effective in non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) gene mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20512075", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 226, "text": "Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with the responses to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with non-small-cell lung cancer (NSCLC).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19063875", "endSection": "sections.0" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1393, "text": "EGFR tyrosine kinase inhibitors (gefitinib, erlotinib), which are molecularly targeted drugs, and it has now become possible to select treatment methods by choosing from a number of anticancer drugs. EGFR tyrosine kinase inhibitors have been demonstrated to have a very high cytoreductive effect on lung cancers that have EGFR gene mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18799900", "endSection": "sections.0" }, { "offsetInBeginSection": 224, "offsetInEndSection": 385, "text": "EGFR gene mutations at kinase domain in non-small cell lung cancer (NSCLC) have been examined for their ability to predict sensitivity to gefitinib or erlotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18726117", "endSection": "sections.0" }, { "offsetInBeginSection": 214, "offsetInEndSection": 386, "text": "responsive patients can relapse as a result of selection for EGFR gene mutations that confer resistance to ATP competitive EGFR inhibitors, such as erlotinib and gefitinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17575237", "endSection": "sections.0" }, { "offsetInBeginSection": 28, "offsetInEndSection": 254, "text": "the epidermal growth factor receptor (EGFR) was a therapeutic target in non-small cell lung cancer (NSCLC) and other cancers led to development of the small-molecule receptor tyrosine kinase inhibitors gefitinib and erlotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17145836", "endSection": "sections.0" }, { "offsetInBeginSection": 1387, "offsetInEndSection": 1501, "text": "There was a significant correlation between EGFR gene copy number, EGFR gene mutations, and gefitinib sensitivity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17145836", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Epidermal growth factor receptor (EGFR) gene mutations have been found in a subset of non-small cell lung cancer (NSCLC) with good clinical response to gefitinib therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16199108", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity such as gefitinib and erlotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16009451", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene are reportedly associated with sensitivity of lung cancers to gefitinib (Iressa), kinase inhibitor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15329413", "endSection": "sections.0" }, { "offsetInBeginSection": 1567, "offsetInEndSection": 1689, "text": "frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15329413", "endSection": "sections.0" } ] }, { "body": "Which protein complexes contain mitofilin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24030101", "http://www.ncbi.nlm.nih.gov/pubmed/23676277", "http://www.ncbi.nlm.nih.gov/pubmed/22252321", "http://www.ncbi.nlm.nih.gov/pubmed/21987634", "http://www.ncbi.nlm.nih.gov/pubmed/22575891", "http://www.ncbi.nlm.nih.gov/pubmed/22014515", "http://www.ncbi.nlm.nih.gov/pubmed/21944719", "http://www.ncbi.nlm.nih.gov/pubmed/22496419", "http://www.ncbi.nlm.nih.gov/pubmed/22918945", "http://www.ncbi.nlm.nih.gov/pubmed/23704930" ], "ideal_answer": [ "mitochondrial inter-membrane space bridging (MIB) complex \nmitochondrial inner membrane organizing system (MINOS)\nMitOS for mitochondrial organizing structure" ], "exact_answer": [ [ "MIB", "mitochondrial inter-membrane space bridging complex" ], [ "MINOS", "mitochondrial inner membrane organizing system" ], [ "MitOS" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016592", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043234", "http://www.uniprot.org/uniprot/FCJ1_LODEL", "http://www.uniprot.org/uniprot/FCJ1_SCLS1", "http://www.uniprot.org/uniprot/FCJ1_CANAL", "http://www.uniprot.org/uniprot/FCJ1_AJECN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046912", "http://www.uniprot.org/uniprot/FCJ1_CANTT" ], "type": "list", "id": "53215fca9b2d7acc7e000005", "snippets": [ { "offsetInBeginSection": 915, "offsetInEndSection": 1062, "text": " and the mitochondrial structural proteins-components of mitochondrial inter-membrane space bridging (MIB) complex (Mitofilin, Sam50, and ChChd3), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24030101", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 362, "text": "Mitofilin/MINOS protein complex ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704930", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 989, "text": " APOOL physically interacts with several subunits of the MINOS complex, namely Mitofilin, MINOS1, and SAMM50. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704930", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1086, "text": "Mitofilin/MINOS protein complex ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704930", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 662, "text": "MINOS subunits (mitofilin, MINOS1, and CHCHD3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23676277", "endSection": "abstract" }, { "offsetInBeginSection": 918, "offsetInEndSection": 950, "text": "mitofilin, a core MINOS subunit,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23676277", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 239, "text": "The mitochondrial inner membrane organizing system (MINOS) is a large protein complex required for maintaining inner membrane architecture. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918945", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 795, "text": "Mitochondria lacking mitofilin, the large core subunit of MINOS,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The mitochondrial inner membrane contains a large protein complex crucial for membrane architecture, the mitochondrial inner membrane organizing system (MINOS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22575891", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 557, "text": " To study if outer membrane interactions and maintenance of cristae morphology are directly coupled, we generated mutant forms of mitofilin/Fcj1 (formation of crista junction protein 1), a core component of MINOS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22575891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The C-terminal domain of Fcj1 is required for formation of crista junctions and interacts with the TOB/SAM complex in mitochondria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496419", "endSection": "title" }, { "offsetInBeginSection": 232, "offsetInEndSection": 291, "text": "Mitofilin/Fcj1, the central component of the MINOS complex,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22014515", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 648, "text": "We provide evidence that the SAM components exist in a large protein complex together with the IMM proteins mitofilin and CHCHD3, which we term the mitochondrial intermembrane space bridging (MIB) complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22252321", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 680, "text": "which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21987634", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 599, "text": "Mitofilin is part of a large inner membrane complex, and we identify five partner proteins as constituents of the mitochondrial inner membrane organizing system (MINOS) that is required for keeping cristae membranes connected to the inner boundary membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21944719", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 813, "text": " Our findings indicate that mitofilin is a central component\u00a0of MINOS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21944719", "endSection": "abstract" } ] }, { "body": "Define marine metaproteomics", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21169428", "http://www.ncbi.nlm.nih.gov/pubmed/23968355", "http://www.ncbi.nlm.nih.gov/pubmed/21068774", "http://www.ncbi.nlm.nih.gov/pubmed/22517752", "http://www.ncbi.nlm.nih.gov/pubmed/23616470", "http://www.ncbi.nlm.nih.gov/pubmed/24112684", "http://www.ncbi.nlm.nih.gov/pubmed/24041543", "http://www.ncbi.nlm.nih.gov/pubmed/23126454", "http://www.ncbi.nlm.nih.gov/pubmed/16176596", "http://www.ncbi.nlm.nih.gov/pubmed/24212578", "http://www.ncbi.nlm.nih.gov/pubmed/24060126", "http://www.ncbi.nlm.nih.gov/pubmed/24060127", "http://www.ncbi.nlm.nih.gov/pubmed/20164862", "http://www.ncbi.nlm.nih.gov/pubmed/22225547", "http://www.ncbi.nlm.nih.gov/pubmed/22399469", "http://www.ncbi.nlm.nih.gov/pubmed/23831146" ], "ideal_answer": [ "Marine metaproteomics is the study of the activities of whole marine microbial communities. The proteomic analyses are applied directly without the need for prior microbial culturing. The samples can be sediments,seawater, etc." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059001" ], "type": "summary", "id": "530a3f8a970c65fa6b000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Metaproteomics is a new field within the 'omics' science which investigates protein expression from a complex biological system and provides direct evidence of physiological and metabolic activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Metaproteomic studies of whole microbial communities from environmental samples (e.g., soil, sediments, freshwater, seawater, etc.) have rapidly increased in recent years due to many technological advances in mass spectrometry (MS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24060127", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 775, "text": "Metatranscriptomics and metaproteomics are approaches based on different techniques and have recently emerged as promising techniques to describe microbial activities within a given environment at the molecular level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23968355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Culture-independent techniques such as LC-MS/MS-based metaproteomic analyses are being increasingly utilized for the study of microbial composition and function in complex environmental samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23831146", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 612, "text": "Metaproteomic analysis and protein-stable isotope probing revealed Burkholderiales, Actinomycetales, and Rhizobiales as the most active microorganisms in the groundwater communities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23616470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Advances in tandem mass spectrometry (tandem MS) and sequencing have enabled the field of community proteomics, which seeks to identify expressed proteins, their sequence variability, and the physiological responses of organisms to variable environmental conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24060126", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 792, "text": "Marine community proteomic studies have verified the importance of nutrient transport, energy generation, and carbon fixation functions in bacteria and archaea and revealed spatial and temporal shifts in the expressed functions of communities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24060126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "Metagenomics is the study of microbial organisms using sequencing applied directly to environmental samples. Similarly, in metatranscriptomics and metaproteomics, the RNA and protein sequences of such samples are studied. The analysis of these kinds of data often starts by asking the questions of \"who is out there?\", \"what are they doing?\", and \"how do they compare?\". ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22399469", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 611, "text": "the study of the proteins collectively expressed by all the microorganisms present within an ecosystem (metaproteomics) is not only crucial but can also provide insights into microbial functionality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22225547", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1133, "text": "Metaproteomics has been employed in very diverse environments, and this review discusses the recent advances achieved in the context of human biology, soil, marine and freshwater environments as well as natural and bioengineered systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22225547", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1317, "text": "To assess the functional dynamics of microbial communities, metatranscriptomics and metaproteomics have been developed. The combination of DNA-based, mRNA-based, and protein-based analyses of microbial communities present in different environments is a way to elucidate the compositions, functions, and interactions of microbial communities and to link these to environmental processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Metaproteomics is one of a suite of new approaches providing insights into the activities of microorganisms in natural environments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21068774", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 465, "text": "We used comparative membrane metaproteomics to identify functional responses of communities to different nutrient concentrations on an oceanic scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20164862", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 396, "text": "This study describes the application of proteomic approaches (metaproteomics) to observe expressed protein profiles of natural microbial communities (metaproteomes). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16176596", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 630, "text": "metaproteomics analysis of fecal samples to determine microbial gut composition and protein expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212578", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 820, "text": "In this study, we used metaproteomics and metabolomics to investigate the intricate network of metabolic interactions in the chemosynthetic association between Olavius algarvensis, a gutless marine worm, and its bacterial symbionts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22517752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "The role of planktonic Flavobacteria in processing algal organic matter in coastal East Antarctica revealed using metagenomics and metaproteomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23126454", "endSection": "title" } ] }, { "body": "Mutation of which gene and which chromosome cause Neurofibromatosis type I?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7522538", "http://www.ncbi.nlm.nih.gov/pubmed/2491777", "http://www.ncbi.nlm.nih.gov/pubmed/7519874", "http://www.ncbi.nlm.nih.gov/pubmed/23399325", "http://www.ncbi.nlm.nih.gov/pubmed/16830335", "http://www.ncbi.nlm.nih.gov/pubmed/21482379", "http://www.ncbi.nlm.nih.gov/pubmed/2491782", "http://www.ncbi.nlm.nih.gov/pubmed/2491780", "http://www.ncbi.nlm.nih.gov/pubmed/2491784", "http://www.ncbi.nlm.nih.gov/pubmed/22962301", "http://www.ncbi.nlm.nih.gov/pubmed/8630973", "http://www.ncbi.nlm.nih.gov/pubmed/16377376", "http://www.ncbi.nlm.nih.gov/pubmed/8768681", "http://www.ncbi.nlm.nih.gov/pubmed/20860891", "http://www.ncbi.nlm.nih.gov/pubmed/20186797", "http://www.ncbi.nlm.nih.gov/pubmed/10633134", "http://www.ncbi.nlm.nih.gov/pubmed/18331998", "http://www.ncbi.nlm.nih.gov/pubmed/22678692", "http://www.ncbi.nlm.nih.gov/pubmed/22312371", "http://www.ncbi.nlm.nih.gov/pubmed/16459992", "http://www.ncbi.nlm.nih.gov/pubmed/20927530", "http://www.ncbi.nlm.nih.gov/pubmed/10787042", "http://www.ncbi.nlm.nih.gov/pubmed/12696059", "http://www.ncbi.nlm.nih.gov/pubmed/2562822" ], "ideal_answer": [ "Neurofibromatosis Type I is an autosomal dominant condition associated with NF-1 gene mutation that is located in the long arm of chromosome 17 (17q11.2). In the majority (95%) of Neurofibromatosis Type I individuals, the mutation is found in the NF1 gene, while the remaining 5% of the patients have different types of genetic abnormalities.\n" ], "exact_answer": [ [ "NF1 gene" ], [ "chromosome 17" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005694", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009456", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016514" ], "type": "list", "id": "5148e1d6d24251bc0500003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The von Recklinghausen neurofibromatosis (NF1) gene has been localized to the pericentromeric region of chromosome 17.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2491777", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Nine markers from the pericentromeric region of chromosome 17 were typed in 16 British and five South African families with neurofibromatosis type 1 (NF1).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2491780", "endSection": "sections.0" }, { "offsetInBeginSection": 305, "offsetInEndSection": 521, "text": "Inspection of recombinant events in families informative for several markers suggests that the NF1 gene is located between the markers EW301 (cen-p11.2) and EW206 (cen-q12) and possibly distal to pHHH202 (q11.2-q12).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2491780", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The gene for von Recklinghausen neurofibromatosis type 1 (NF1) has recently been mapped to the pericentromeric region of human chromosome 17.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2491782", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "In addition to reporting, in accompanying papers, their individual analyses of mapping the neurofibromatosis type 1 (NF1) gene on chromosome 17, members of the International Consortium for NF1 Linkage contributed their data for our joint analysis to determine the exact sequence of flanking markers and to obtain precise estimates and confidence limits of the recombination fractions for the closest markers, in anticipation of clinical use.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2491784", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "To better map the location of the von Recklinghausen neurofibromatosis (NF1) gene, we have characterized a somatic cell hybrid designated 7AE-11. This microcell-mediated, chromosome-transfer construct harbors a centromeric segment and a neo-marked segment from the distal long arm of human chromosome 17.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2562822", "endSection": "sections.0" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1310, "text": "The cosmids in the NF1 region will be an important resource for testing DNA blots of large-fragment restriction-enzyme digests from NF1 patient cell lines, to detect rearrangements in patients' DNA and to identify the 17;22 NF1 translocation breakpoint.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2562822", "endSection": "sections.0" }, { "offsetInBeginSection": 740, "offsetInEndSection": 950, "text": "The frequent LOH surrounding the NF1 locus and lack of neurofibromin expression in these tumors suggest that NF1 gene mutations may contribute to the development of adrenal gland neoplasms in patients with NF1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7519874", "endSection": "sections.0" }, { "offsetInBeginSection": 676, "offsetInEndSection": 813, "text": "In the latter, the breakpoint in 17q occurred below the centromere and is at or in the region of the Neurofibromatosis Type 1 (NF1) gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8630973", "endSection": "sections.0" }, { "offsetInBeginSection": 158, "offsetInEndSection": 362, "text": "Neurofibromatosis type I (NF1) is an autosomal dominant condition associated with mutations in the long arm of chromosome 17, and characterised by neurofibromas, caf\u00e9-au-lait spots and axillary freckling.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10787042", "endSection": "sections.0" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1159, "text": "In addition, the mother's and maternal grandmother's genetic analysis showed identical mutations in the neurofibromatosis I gene on the long arm of chromosome 17, confirming the diagnosis of NF1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10787042", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Duplicon-mediated microdeletions around the NF1 gene are frequently associated with a severe form of neurofibromatosis type I in a subgroup of patients who show an earlier onset of cutaneous neurofibromas, dysmorphic facial features, and lower IQ values.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12696059", "endSection": "sections.0" }, { "offsetInBeginSection": 238, "offsetInEndSection": 405, "text": "Neurofibromatosis had been diagnosed in infancy, and genetic testing showed that the patient had a mutation in chromosome 17, consistent with neurofibromatosis type I.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16377376", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Neurofibromatosis Type 1 (NF1) is one of the most common inherited diseases in humans. It is caused by a mutation in the NF1 gene on chromosome 17, and is associated with numerous central and peripheral nervous system manifestations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16459992", "endSection": "sections.0" }, { "offsetInBeginSection": 144, "offsetInEndSection": 339, "text": "In 95% of NF1 individuals, a mutation is found in the NF1 gene, and in 5% of the patients, the germline mutation consists of a microdeletion that includes the NF1 gene and several flanking genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16830335", "endSection": "sections.0" }, { "offsetInBeginSection": 493, "offsetInEndSection": 986, "text": "Herein, we describe a unique case of anaplastic de novo astroblastoma-sarcoma, in essence a variant of gliosarcoma, occurring in a 50-year-old female with documented NF1. Genetic study (fluorescence in situ hybridization) demonstrated no chromosomal losses or gains. Testing for abnormalities of chromosomes 7, 9, 10, 12, 17, 19 and 20, including the EGFR, p16, PTEN, MDM2 and NF1 gene regions, we found the tumor to exhibit a deletion of PTEN, monosomy 17 and gains of chromosomes 19 and 20q.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20860891", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Neurofibromatosis type I (NF1) is an autosomal dominant disorder affecting 1 in 3000 people. The NF1 gene is located on chromosome 17q11.2, spans 350 kb of genomic DNA, and contains 60 exons.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10633134", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 476, "text": "A patient with recurrent-remittent multiple sclerosis associated with neurofibromatosis type I is described. The case is interesting for two reasons: 1) the difficulty of evaluating MRI findings, since both entities involve similar anomalies and 2) the relation between the two entities, according to evidence from recent genetic studies showing that the myelin protein gene associated to oligodendrocytes is part of an intron of the neurofibromatosis-1 gene of chromosome 17.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8768681", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Neurofibromatosis type I (NFI) is a common autosomal dominant disorder with an increased risk for developing benign and malignant tumors. The NFI gene has been cloned and maps to 17q11.2, and the gene product acts as a tumor suppressor gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7522538", "endSection": "sections.0" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1071, "text": "Direct sequencing of the NF1 gene in tumor DNA identified the presence of an inactivating NF1 somatic mutation in 41% (25/61) of analyzed sporadic tumors, associated with loss of the wild-type allele in 84% (21/25) of cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22962301", "endSection": "sections.0" }, { "offsetInBeginSection": 453, "offsetInEndSection": 567, "text": "A novel mutation c.4821delA was identified in NF1 gene, which predicted truncation of neurofibromin (p.Leu1607fs).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22678692", "endSection": "sections.0" }, { "offsetInBeginSection": 609, "offsetInEndSection": 675, "text": "She had a genotype of heterozygous c.6709C>T mutation of NF1 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21482379", "endSection": "sections.0" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1166, "text": "RESULTS: The mutational analysis of the NF1 gene revealed a novel frameshift insertion mutation in exon 4c (c.654 ins A) in all affected family members.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20927530", "endSection": "sections.0" }, { "offsetInBeginSection": 675, "offsetInEndSection": 883, "text": "Using lymphoblastoid, fibroblast, and buccal cell samples collected from both twins and from other family members in three generations, we discovered a pathogenic nonsense mutation in exon 40 of the NF1 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20186797", "endSection": "sections.0" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1269, "text": "We also found a novel non-synonymous change in exon 16 of the NF1 gene that was transmitted from the unaffected mother to both twins and co-segregated with the pathogenic mutation in the ensuing generation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20186797", "endSection": "sections.0" }, { "offsetInBeginSection": 254, "offsetInEndSection": 385, "text": "The disease gene of the Chinese NF1 family was linked to NF1 locus, and a nonsense mutation, G1336X in the NF1 gene was identified.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18331998", "endSection": "sections.0" }, { "offsetInBeginSection": 574, "offsetInEndSection": 687, "text": "The present study demonstrated that G1336X mutation in the NF1 gene cause Neurofibromatosis type I in the family.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18331998", "endSection": "sections.0" } ] }, { "body": "Which genes does thyroid hormone receptor alpha1 regulate in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19171649", "http://www.ncbi.nlm.nih.gov/pubmed/15808842", "http://www.ncbi.nlm.nih.gov/pubmed/15831522", "http://www.ncbi.nlm.nih.gov/pubmed/23532677", "http://www.ncbi.nlm.nih.gov/pubmed/17317766", "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "http://www.ncbi.nlm.nih.gov/pubmed/18622044", "http://www.ncbi.nlm.nih.gov/pubmed/20228172", "http://www.ncbi.nlm.nih.gov/pubmed/19832729", "http://www.ncbi.nlm.nih.gov/pubmed/19629520", "http://www.ncbi.nlm.nih.gov/pubmed/16155104", "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "http://www.ncbi.nlm.nih.gov/pubmed/14704232" ], "ideal_answer": [ "\u03b2-myosin heavy chain, alpha-myosin heavy chain, SR(Ca)ATPase, phospholamban, nucleotide-gated potassium channel 2, KCNE1, HCN2, HCN4, KCND2, KCND3, KCNA4" ], "exact_answer": [ [ "\u03b2-myosin heavy chain" ], [ "alpha-myosin heavy chain" ], [ "SR(Ca)ATPase" ], [ "phospholamban" ], [ "nucleotide-gated potassium channel 2" ], [ "KCNE1" ], [ "HCN2" ], [ "HCN4" ], [ "KCND2" ], [ "KCND3" ], [ "KCNA4" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861" ], "type": "list", "id": "515c4f05298dcd4e51000006", "snippets": [ { "offsetInBeginSection": 547, "offsetInEndSection": 643, "text": "A group of mice was treated with debutyl-dronedarone (DBD), a selective TR\u03b11 inhibitor (AMI-DBD)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23532677", "endSection": "sections.0" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1435, "text": "Furthermore, AMI resulted in \u03b2-myosin heavy chain overexpression and reduction in the ratio of SR(Ca)ATPase to phospholamban (PLB). The latter further declined in AMI-DBD mainly due to increased expression of PLB", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23532677", "endSection": "sections.0" }, { "offsetInBeginSection": 501, "offsetInEndSection": 774, "text": "We identified that mice expressing the mutant TRalpha1R384C (TRalpha1+m mice) displayed a mild bradycardia, which becomes more pronounced during night activity or on stress and is accompanied by a reduced expression of nucleotide-gated potassium channel 2 mRNA in the heart", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20228172", "endSection": "sections.0" }, { "offsetInBeginSection": 794, "offsetInEndSection": 863, "text": "KCNE1 was four to 10-fold overexpressed in mice deficient in TRalpha1", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19832729", "endSection": "sections.0" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1542, "text": "The bradycardia and prolonged QT(end) time in hypothyroid states can be explained by altered K(+) channel function due to decreased TRalpha1-dependent repression of KCNE1 expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19832729", "endSection": "sections.0" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1107, "text": "Consistently, TR alpha 1-infected myocytes exhibited larger I(f) current densities along with increased HCN2 and HCN4 mRNA and protein levels.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19629520", "endSection": "sections.0" }, { "offsetInBeginSection": 530, "offsetInEndSection": 649, "text": "T3 stimulation enhanced KCND2 and KCND3 expression and decreased KCNA4 transcription, while KCNIP2 remained unaffected.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19171649", "endSection": "sections.0" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1010, "text": "TRalpha1 increased I(to), while TRbeta1 significantly reduced I(to) in size, which was associated with TRalpha1-mediated increase and TRbeta1-mediated reduction of KCND2/3 transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19171649", "endSection": "sections.0" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1474, "text": "While the TRalpha1 aporeceptor enhanced KCND3 transcription, the TRbeta1 aporeceptor suppressed KCND3 expression, with both effects exhibiting ligand-dependent amplification upon T3 stimulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19171649", "endSection": "sections.0" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1097, "text": "PE, in the absence of T3, resulted in 5.0 fold increase in TRalpha1 expression in nucleus and 2.0 fold decrease in TRalpha1 expression in cytosol, P<0.05. As a result, a fetal pattern of myosin isoform expression with marked expression of beta-MHC was observed in PE treated vs the untreated cells, P<0.05.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18622044", "endSection": "sections.0" }, { "offsetInBeginSection": 1597, "offsetInEndSection": 2002, "text": "PKC alpha overexpression in cardiomyocytes caused marked repression of triiodothyronine (T3)-responsive genes, alpha-myosin heavy chain, and the sarcoplasmic reticulum calcium-activated adenosinetriphosphatase SERCA2. Treatment with T3 for 4 h resulted in significant reductions of PKC alpha in nuclear and cytosolic compartments, and decreased TR alpha1 mRNA and protein, with normalization of phenotype.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16155104", "endSection": "sections.0" }, { "offsetInBeginSection": 444, "offsetInEndSection": 618, "text": "The mechanism of TH and TRalpha1-specific hypertrophy is novel for a nuclear hormone receptor and involves the transforming growth factor beta-activated kinase (TAK1) and p38", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831522", "endSection": "sections.0" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1383, "text": "Excised TRalpha(1)+/m hearts showed an increased expression of phospholamban (PLB)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15808842", "endSection": "sections.0" }, { "offsetInBeginSection": 112, "offsetInEndSection": 290, "text": "administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "endSection": "sections.0" }, { "offsetInBeginSection": 776, "offsetInEndSection": 976, "text": "lpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "endSection": "sections.0" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1424, "text": "The activity of TR DNA binding to the transcriptional regulatory region in the alpha-MHC and SR Ca(2+)-ATPase genes and the mRNA and protein expression of alpha-MHC and SR Ca(2+)-ATPase in the heart and plasma 3,3'-triiodothyronine and thyroxine levels were altered in association with changes in the myocardial TR protein levels.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "endSection": "sections.0" }, { "offsetInBeginSection": 1173, "offsetInEndSection": 1441, "text": "addition, TR cotransfection and treatment with the TRbeta1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1, and TRalpha1 to alpha-MyHC transcription and increased myocyte size", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "OBJECTIVE: The reduced heart rate and prolonged QT(end) duration in mice deficient in thyroid hormone receptor (TR) alpha1 may involve aberrant expression of the K(+) channel alpha-subunit KCNQ1 and its regulatory beta-subunit KCNE1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19832729", "endSection": "sections.0" } ] }, { "body": "What is the content of the METLIN database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23185759", "http://www.ncbi.nlm.nih.gov/pubmed/25496351", "http://www.ncbi.nlm.nih.gov/pubmed/16404815", "http://www.ncbi.nlm.nih.gov/pubmed/23631600", "http://www.ncbi.nlm.nih.gov/pubmed/21696903", "http://www.ncbi.nlm.nih.gov/pubmed/22768229", "http://www.ncbi.nlm.nih.gov/pubmed/24015273", "http://www.ncbi.nlm.nih.gov/pubmed/19137116", "http://www.ncbi.nlm.nih.gov/pubmed/23593322", "http://www.ncbi.nlm.nih.gov/pubmed/25322782", "http://www.ncbi.nlm.nih.gov/pubmed/23829391", "http://www.ncbi.nlm.nih.gov/pubmed/20810534", "http://www.ncbi.nlm.nih.gov/pubmed/23391889", "http://www.ncbi.nlm.nih.gov/pubmed/17951291", "http://www.ncbi.nlm.nih.gov/pubmed/25462372", "http://www.ncbi.nlm.nih.gov/pubmed/18627180", "http://www.ncbi.nlm.nih.gov/pubmed/15801754" ], "ideal_answer": [ "METLIN is a metabolite database containing tandem mass spectrometry data for each metabolite." ], "exact_answer": [ "METLIN is a metabolite database containing tandem mass spectrometry data for each metabolite." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030562" ], "type": "factoid", "id": "54d662113706e8952800000d", "snippets": [ { "offsetInBeginSection": 705, "offsetInEndSection": 843, "text": " The tandem mass spectrometry data acquisition enabled automatic search and matching against the METLIN tandem mass spectrometry database,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25496351", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1178, "text": "the METLIN metabolomics database", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25462372", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 715, "text": "Numbers of unique metabolites that are specific to a particular sample preparation approach were also identified by online available database, Metlin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25322782", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 971, "text": "Metlin metabolomics database", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24015273", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1467, "text": "METLIN metabolite database", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23829391", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 500, "text": " Following high mass accuracy data analysis using MS and MS/MS, metabolites were identified by searching against major metabolite databases including METLIN", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23631600", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 902, "text": "Untargeted features were annotated via matching to the METLIN metabolite database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391889", "endSection": "title" }, { "offsetInBeginSection": 641, "offsetInEndSection": 667, "text": "ETLIN metabolite database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23391889", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 755, "text": " The correlated metabolin and their metabolic pathways were identified using Metlin Database. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185759", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 334, "text": " Major metabolite databases include Human Metabolome DataBase (HMDB), Madison Metabolomics Consortium Database (MMCD), Metlin, and LIPID MAPS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768229", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 942, "text": "METLIN accurate mass matching database (DB) established according to those reported in the literatures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21696903", "endSection": "abstract" }, { "offsetInBeginSection": 1291, "offsetInEndSection": 1318, "text": "METLIN Metabolite Database ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "METLIN: a metabolite mass spectral database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16404815", "endSection": "title" }, { "offsetInBeginSection": 380, "offsetInEndSection": 636, "text": " METLINincludes an annotated list of known metabolite structural information that is easily cross-correlated with its catalogue of high-resolution Fourier transform mass spectrometry (FTMS) spectra, tandem mass spectrometry (MS/MS) spectra, and LC/MS data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16404815", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 623, "text": "online database (METLIN) to find and identify metabolites ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17951291", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 517, "text": "high quality experimental MS/MS data from known metabolites contained in a reference library (METLIN). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18627180", "endSection": "abstract" } ] }, { "body": "Which is the RNA sequence of the canonical polyadenylation signal?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22535384", "http://www.ncbi.nlm.nih.gov/pubmed/22056681", "http://www.ncbi.nlm.nih.gov/pubmed/21943048", "http://www.ncbi.nlm.nih.gov/pubmed/24152550", "http://www.ncbi.nlm.nih.gov/pubmed/19169861", "http://www.ncbi.nlm.nih.gov/pubmed/19041263", "http://www.ncbi.nlm.nih.gov/pubmed/19509282", "http://www.ncbi.nlm.nih.gov/pubmed/24177577", "http://www.ncbi.nlm.nih.gov/pubmed/22306880", "http://www.ncbi.nlm.nih.gov/pubmed/19032167", "http://www.ncbi.nlm.nih.gov/pubmed/19597839", "http://www.ncbi.nlm.nih.gov/pubmed/18658125" ], "ideal_answer": [ "A polyadenylation signal (AAUAAA) nearby the 3' end of pre-mRNA is required for poly(A) synthesis." ], "exact_answer": [ "AAUAAA" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006378", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039104", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043631" ], "type": "factoid", "id": "550739cf3b8a5dc045000002", "snippets": [ { "offsetInBeginSection": 373, "offsetInEndSection": 430, "text": ". Two putative polyadenylation signal sequences (AATAAA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169861", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 435, "text": "polyadenylation signal sequence AATAAA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19041263", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 117, "text": "The most canonical AAUAAA hexamer ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19032167", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 362, "text": "polyadenylation signal site (AATAAA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24177577", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 330, "text": "the canonical AATAAA motif ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152550", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 717, "text": "with a classical polyadenylation signal sequence AATAAA,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22535384", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 237, "text": "AATAAA hexanucleotide polyadenylation signal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22306880", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 447, "text": "olyadenylation signal site (AATAAA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056681", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 411, "text": "polyadenylation signal AATAAA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21943048", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 54, "text": "polyadenylation signal AAUAAA ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19597839", "endSection": "title" }, { "offsetInBeginSection": 389, "offsetInEndSection": 418, "text": "polyadenylation signal AAUAAA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509282", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 176, "text": "A polyadenylation signal (AAUAAA) nearby the 3' end of pre-mRNA is required for poly(A) synthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18658125", "endSection": "abstract" } ] }, { "body": "Which computational frameworks are available for predicting enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "http://www.ncbi.nlm.nih.gov/pubmed/23382538" ], "ideal_answer": [ "DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics. Experimental results indicate that DEEP performs better than four state-of-the-art methods on the ENCODE data. The PRISM (predicting regulatory information from single motifs) approach obtains 2543 TF function predictions in a large variety of contexts, at a false discovery rate of 16%. The predictions are highly enriched for validated TF roles, and 45 of 67 (67%) tested binding site regions in five different contexts act as enhancers in functionally matched cells." ], "exact_answer": [ [ "DEEP" ], [ "PRISM" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004742", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019295" ], "type": "list", "id": "56ae40110a360a5e45000009", "snippets": [ { "offsetInBeginSection": 672, "offsetInEndSection": 1646, "text": "In this study we developed DEEP, a novel ensemble prediction framework. DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. In our method we train many individual classification models that we combine to classify DNA regions as enhancers or non-enhancers. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics. Experimental results indicate that DEEP performs better than four state-of-the-art methods on the ENCODE data. We report the first computational enhancer prediction results on FANTOM5 data where DEEP achieves 90.2% accuracy and 90% geometric mean (GM) of specificity and sensitivity across 36 different tissues. We further present results derived using in vivo-derived enhancer data from VISTA database. DEEP-VISTA, when tested on an independent test set, achieved GM of 80.1% and accuracy of 89.64%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1552, "text": "Our novel PRISM (predicting regulatory information from single motifs) approach obtains 2543 TF function predictions in a large variety of contexts, at a false discovery rate of 16%. The predictions are highly enriched for validated TF roles, and 45 of 67 (67%) tested binding site regions in five different contexts act as enhancers in functionally matched cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "DEEP: a general computational framework for predicting enhancers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "endSection": "title" }, { "offsetInBeginSection": 1262, "offsetInEndSection": 1461, "text": "We report the first computational enhancer prediction results on FANTOM5 data where DEEP achieves 90.2% accuracy and 90% geometric mean (GM) of specificity and sensitivity across 36 different tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "DEEP: a general computational framework for predicting enhancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "endSection": "title" } ] }, { "body": "Which proteins in the cerebro-spinal fluid can be used for early diagnosis of Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19324376", "http://www.ncbi.nlm.nih.gov/pubmed/10510805", "http://www.ncbi.nlm.nih.gov/pubmed/21996556", "http://www.ncbi.nlm.nih.gov/pubmed/19363993", "http://www.ncbi.nlm.nih.gov/pubmed/24133408", "http://www.ncbi.nlm.nih.gov/pubmed/15975056", "http://www.ncbi.nlm.nih.gov/pubmed/21941496", "http://www.ncbi.nlm.nih.gov/pubmed/8180825", "http://www.ncbi.nlm.nih.gov/pubmed/20538373", "http://www.ncbi.nlm.nih.gov/pubmed/21386929", "http://www.ncbi.nlm.nih.gov/pubmed/9129722", "http://www.ncbi.nlm.nih.gov/pubmed/19278690", "http://www.ncbi.nlm.nih.gov/pubmed/21971452", "http://www.ncbi.nlm.nih.gov/pubmed/14699432", "http://www.ncbi.nlm.nih.gov/pubmed/20558869", "http://www.ncbi.nlm.nih.gov/pubmed/11204323", "http://www.ncbi.nlm.nih.gov/pubmed/21903360", "http://www.ncbi.nlm.nih.gov/pubmed/2384121" ], "ideal_answer": [ "CSF is a clear fluid that bathes and cushions the brain and spinal cord. Adults have about 1 pint of CSF, which physicians can sample through a minimally invasive procedure called a lumbar puncture, or spinal tap. Research suggests that Alzheimer's disease in its earliest stages may cause changes in CSF levels of tau and beta-amyloid, two proteins that form abnormal brain deposits strongly linked to the disease." ], "exact_answer": [ [ "phosphorylated tau" ], [ "beta-amyloid" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016229" ], "type": "list", "id": "5311d130e3eabad021000009", "snippets": [ { "offsetInBeginSection": 32, "offsetInEndSection": 337, "text": "Alzheimer's disease (AD) patients have reduced amyloid (A\u03b2 1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau 181p) in the cerebro-spinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly (CN) and mild cognitive impairment (MCI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21971452", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1199, "text": "although high CSF tau and low CSF A\u03b242 are predictive of Alzheimer's disease, the criterion \"positive CSF tau/A\u03b242 ratio\" is not well defined. The qualification of biomarkers in the pre-dementia stage of Alzheimer's disease will allow better inclusion criteria of patients in pre-dementia trials in which the benefit/risk is higher for treatment with these novel compounds", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903360", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 238, "text": "investigate the dynamics of four of the most validated biomarkers for Alzheimer's disease (AD), cerebro-spinal fluid (CSF) Abeta 1-42, tau, hippocampal volume, and FDG-PET, in patients at different stage of AD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538373", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 464, "text": "Alzheimer's disease (AD) may be facilitated by cerebro-spinal fluid (CSF) biomarkers in combination with imaging and clinical assessments. By determining the concentration of beta amyloid fragments, total tau (t-tau) and phospho-tau (p-tau), it is possible to detect the conversion of mild cognitive impairment (MCI) to AD or distinguish AD vs. pseudo-dementia. However, these markers are poorly sensitive to the progressive disease stages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19278690", "endSection": "abstract" } ] }, { "body": "Is there evidence for somatic mosaicism in Tuberous Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9361032", "http://www.ncbi.nlm.nih.gov/pubmed/16237225" ], "ideal_answer": [ "Yes, somatic mosaicism in Tuberous Sclerosis has been documented with the use of mutation identification, and subsequent linkage analysis in the affected families. In a large family with both parents unaffected, 3 affected children and 5 unaffected siblings, a 4 bp insertion in TSC2 gene was shown to be inherited from the mother." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009030", "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ], "type": "yesno", "id": "53177803b166e2b80600000e", "snippets": [ { "offsetInBeginSection": 158, "offsetInEndSection": 330, "text": "There are several case reports of solitary SEGA without any other manifestations of TSC. Usually these cases are thought to be forme fruste of TSC due to somatic mosaicism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16237225", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Female germline mosaicism in tuberous sclerosis confirmed by molecular genetic analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9361032", "endSection": "title" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1559, "text": "This is the first case of germline mosaicism in tuberous sclerosis proven by molecular genetic analysis and also the first example of female germline mosaicism for a characterized autosomal dominant gene mutation apparently not associated with somatic mosaicism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9361032", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 1296, "text": "Mutation screening by RT-PCR and direct sequencing of the TSC2 gene identified a 4 bp insertion TACT following nucleotide 2077 in exon 18 which was present in the three affected children but not in five unaffected siblings or the parents. This mutation would cause a frameshift and premature termination at codon 703. Absence of the mutation in lymphocyte DNA from the parents was consistent with germline mosaicism and this was confirmed by our finding of identical chromosome 16 haplotypes in affected and unaffected siblings, providing unequivocal evidence of two different cell lines in the gametes. Molecular analysis of the TSC2 alleles present in the affected subjects showed that the mutation had been inherited from the mother.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9361032", "endSection": "abstract" } ] }, { "body": "What is GRO-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19056941", "http://www.ncbi.nlm.nih.gov/pubmed/24304890", "http://www.ncbi.nlm.nih.gov/pubmed/21549415" ], "ideal_answer": [ "Global run-on sequencing (Gro-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome." ], "type": "summary", "id": "56e0869351531f7e33000011", "snippets": [ { "offsetInBeginSection": 57, "offsetInEndSection": 339, "text": "We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19056941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Global run-on sequencing (GRO-seq) is a recent addition to the series of high-throughput sequencing methods that enables new insights into transcriptional dynamics within a cell. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "Global run-on sequencing (GRO-seq) is a recent addition to the series of high-throughput sequencing methods that enables new insights into transcriptional dynamics within a cell. However, GRO-sequencing presents new algorithmic challenges, as existing analysis platforms for ChIP-seq and RNA-seq do not address the unique problem of identifying transcriptional units de novo from short reads located all across the genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 423, "text": " Global run-on sequencing (GRO-seq) is a recent addition to the series of high-throughput sequencing methods that enables new insights into transcriptional dynamics within a cell. However, GRO-sequencing presents new algorithmic challenges, as existing analysis platforms for ChIP-seq and RNA-seq do not address the unique problem of identifying transcriptional units de novo from short reads located all across the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "Global run-on sequencing (GRO-seq) is a recent addition to the series of high-throughput sequencing methods that enables new insights into transcriptional dynamics within a cell. However, GRO-sequencing presents new algorithmic challenges, as existing analysis platforms for ChIP-seq and RNA-seq do not address the unique problem of identifying transcriptional units de novo from short reads located all across the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304890", "endSection": "abstract" } ] }, { "body": "What is the role of the RUNX1-MYEF2 complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22801375" ], "ideal_answer": [ "A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells." ], "exact_answer": [ "The repression of hematopoietic genes in erythroid cells." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D041905", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015672", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006412" ], "type": "factoid", "id": "56ae70050a360a5e4500000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "endSection": "title" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1086, "text": "Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. Knockdown of Myef2 expression in developing zebrafish results in a reduced number of HSC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1087, "text": "Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. Knockdown of Myef2 expression in developing zebrafish results in a reduced number of HSC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 997, "text": "Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and microarray expression analysis were used to show that RUNX1 binds approximately 9,000 target sites in erythroid cells and is primarily active in the undifferentiated state. Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "endSection": "abstract" } ] }, { "body": "Does smoking increase risk for glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2319291", "http://www.ncbi.nlm.nih.gov/pubmed/17372252", "http://www.ncbi.nlm.nih.gov/pubmed/19568697", "http://www.ncbi.nlm.nih.gov/pubmed/19022673", "http://www.ncbi.nlm.nih.gov/pubmed/21742680", "http://www.ncbi.nlm.nih.gov/pubmed/19494549", "http://www.ncbi.nlm.nih.gov/pubmed/20487573", "http://www.ncbi.nlm.nih.gov/pubmed/16217772", "http://www.ncbi.nlm.nih.gov/pubmed/19107440", "http://www.ncbi.nlm.nih.gov/pubmed/15685439" ], "ideal_answer": [ "No. Smoking does not increase risk for glioblastoma." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012907", "http://www.disease-ontology.org/api/metadata/DOID:3073", "http://www.disease-ontology.org/api/metadata/DOID:3068" ], "type": "yesno", "id": "550e7d6aa103b7801600000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742680", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1380, "text": "No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742680", "endSection": "abstract" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1926, "text": "Non-smokers with G/A and A/A genotype showed increased glioma risk compared with G/G genotype (adjusted OR = 1.72, 95%CI: 1.29-2.30, p = 0.0002 and adjusted OR = 1.81, 95%CI: 1.10-2.99, p = 0.020, respectively). This association was not found in ever- or current-smokers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20487573", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1363, "text": "There was no significant association between glioma and alcohol consumption, smoking and mobile phone use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19494549", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1565, "text": "RESULTS: We found no associations between the GSTM3, GSTP1, NQO1, CYP1A1, GSTM1, or GSTT1 polymorphisms and adult brain tumor risk with the possible exception of a weak association between the G-C (Val-Ala) GSTP1 105/114 haplotype and glioma [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54, 0.99], nor was there an interaction between the effects of the GSTM3 or GSTP1 polymorphisms and cigarette smoking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17372252", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1029, "text": "We did not find any evidence for an association with life-style characteristics such as cigarette smoking, alcohol consumption, use of drugs of any kind, or dietary intake of cured or smoked meat or fish.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2319291", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1230, "text": "No relation was observed between glioma risk and smoking (odds ratio = 0", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742680", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1824, "text": "Compared with nonsmokers, duration of cigarette smoking, number of cigarettes smoked per day and pack-years of smoking were associated with increased glioma risk, although the increases in risk were relatively modest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16217772", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1210, "text": "Among ever smokers, women who reported having quit smoking had a 51% increase in risk of glioma compared with never smokers (HR = 1.51, 95% CI = 0.97-2.34), while current smokers did not appear to have an increase in risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16217772", "endSection": "abstract" } ] }, { "body": "Which genes are implicated in short QT syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17497253", "http://www.ncbi.nlm.nih.gov/pubmed/14676148", "http://www.ncbi.nlm.nih.gov/pubmed/15890322", "http://www.ncbi.nlm.nih.gov/pubmed/19013996", "http://www.ncbi.nlm.nih.gov/pubmed/15159330", "http://www.ncbi.nlm.nih.gov/pubmed/16226079", "http://www.ncbi.nlm.nih.gov/pubmed/22155372", "http://www.ncbi.nlm.nih.gov/pubmed/20126594", "http://www.ncbi.nlm.nih.gov/pubmed/18382206", "http://www.ncbi.nlm.nih.gov/pubmed/16076272", "http://www.ncbi.nlm.nih.gov/pubmed/17432514", "http://www.ncbi.nlm.nih.gov/pubmed/15828882", "http://www.ncbi.nlm.nih.gov/pubmed/19804087", "http://www.ncbi.nlm.nih.gov/pubmed/21383000", "http://www.ncbi.nlm.nih.gov/pubmed/19340359", "http://www.ncbi.nlm.nih.gov/pubmed/16887036", "http://www.ncbi.nlm.nih.gov/pubmed/21798421", "http://www.ncbi.nlm.nih.gov/pubmed/21593722", "http://www.ncbi.nlm.nih.gov/pubmed/21130771" ], "ideal_answer": [ "The genes that are implicated in short QT syndrome are KCNJ2, KCNH2, CACNA2D1 and KCNQ1." ], "exact_answer": [ [ "KCNJ2", "inward rectifier potassium channel gene" ], [ "HERG", "KCNH2" ], [ "CACNA2D1" ], [ "KCNQ1" ], [ "CACNB2b" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "list", "id": "52f509232059c6d71c00001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155372", "endSection": "title" }, { "offsetInBeginSection": 1504, "offsetInEndSection": 1603, "text": "In this study, we identified a novel KCNJ2 gain-of-function mutation, M301K, associated with SQTS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155372", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 756, "text": "A mutation in genes related to SQTS was found in 23% of the probands; most of them had a gain of function mutation in HERG (SQTS1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21798421", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 379, "text": "We present, for the first time, a novel loss-of-function mutation coding for an L-type calcium channel subunit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21383000", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 971, "text": "however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G > C; amino acid p.Ser755Thr), coding for the Ca(v)\u03b1(2)\u03b4-1 subunit of the L-type calcium channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21383000", "endSection": "abstract" }, { "offsetInBeginSection": 1993, "offsetInEndSection": 2122, "text": "In the present study, we report the first pathogenic mutation in the CACNA2D1 gene in humans, which causes a new variant of SQTS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21383000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "A novel mutation in the KCNH2 gene associated with short QT syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21130771", "endSection": "title" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1483, "text": "The altered function of T618I-HERG channels suggests that this mutation in the KCNH2 gene is responsible for the SQTS phenotype in this family. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21130771", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 785, "text": "Gain of function mutations in three genes encoding K(+) channels have been identified, explaining the abbreviated repolarization seen in this condition: KCNH2 for I(kr) (SQT1), KCNQ1 for I(ks) (SQT2) and KCNJ2 for I(k1) (SQT3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20126594", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 519, "text": "To evaluate the possible diagnosis of SQTS, DNA sequencing of genes known to be associated with SQTS was performed and identified a novel mutation in the KCNH2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19340359", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 280, "text": "The mutation of genes (KCNH2, KCNQ1, and KCNJ2) encoding for cardiac potassium channels plays a central role in SQTS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19013996", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 272, "text": "To date, different mutations in genes encoding for cardiac ion channels (KCNH2, KCNQ1, and KCNJ2) have been identified to cause the short QT syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17497253", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 527, "text": "Mutations in 3 different genes KCNQ1, KCNH2, and KCNJ2, all encoding cardiac ionic potassium channels have been identified in affected patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17432514", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 490, "text": "Genetic analysis has, to date, identified three distinct forms of the condition, involving gain-of-function mutations to three different cardiac potassium channel genes: KCNH2 (SQT1), KCNQ1 (SQT2) and KCNJ2 (SQT3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19804087", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 303, "text": "Three different gain-of-function mutations in genes encoding for cardiac potassium channels (KCNH2, KCNQ1, and KCNJ2) have been identified up to now to cause short QT syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16226079", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 272, "text": "To date, three different mutations in genes encoding cardiac ion channels (KCNH2, KCNQ1 and KCNJ2) have been identified as causing short QT syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16076272", "endSection": "abstract" } ] }, { "body": "What is SCENAR therapy used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20396722", "http://www.ncbi.nlm.nih.gov/pubmed/20879466", "http://www.ncbi.nlm.nih.gov/pubmed/16924799", "http://www.ncbi.nlm.nih.gov/pubmed/8779182" ], "ideal_answer": [ "all patients experienced substantial relief of pain from the first treatment. an electronic biofeedback device (scenar) may be successfully utilized in the management of post-herpetic neuralgia. scenar) as effective in the treatment of neurogenic dysfunction of the bladder in children with nocturnal enuresis. post-herpetic neuralgia using a bioelectronical device (scenar). addition of scenar therapy to the complex conventional pharmacotherapy fastened ulcer healing, increased the effectiveness of helicobacter pylori eradication, and improved the condition of the gastroduodenal mucosa. scenar therapy to patients with localized suppurative peritonitis in the postoperative period. a new technique of low-frequency modulated electric current therapy, scenar therapy, was used in treatment of 103 patients with duodenal ulcer (du). ", "localized suppurative peritonitis in the postoperative period\nmanagement of post-herpetic neuralgia\ntreatment of 103 patients with duodenal ulcer\ntreatment of neurogenic dysfunction of the bladder in children with nocturnal enuresis" ], "exact_answer": [ [ "peritonitis postoperative" ], [ "pain in postherpetic neuralgia" ], [ "duodenal ulcer" ], [ "nocturnal enuresis" ] ], "type": "list", "id": "535d69177d100faa09000003", "snippets": [ { "offsetInBeginSection": 48, "offsetInEndSection": 141, "text": "SCENAR therapy to patients with localized suppurative peritonitis in the postoperative period", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20396722", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 157, "text": "post-herpetic neuralgia using a bioelectronical device (SCENAR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20879466", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 474, "text": "All patients experienced substantial relief of pain from the first treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20879466", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 831, "text": "An electronic biofeedback device (SCENAR) may be successfully utilized in the management of post-herpetic neuralgia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20879466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "A new technique of low-frequency modulated electric current therapy, SCENAR therapy, was used in treatment of 103 patients with duodenal ulcer (DU).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16924799", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 648, "text": "Addition of SCENAR therapy to the complex conventional pharmacotherapy fastened ulcer healing, increased the effectiveness of Helicobacter pylori eradication, and improved the condition of the gastroduodenal mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16924799", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 184, "text": "SCENAR) as effective in the treatment of neurogenic dysfunction of the bladder in children with nocturnal enuresis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8779182", "endSection": "abstract" } ] }, { "body": "List symptoms of Gradenigo's syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22696630", "http://www.ncbi.nlm.nih.gov/pubmed/22978305", "http://www.ncbi.nlm.nih.gov/pubmed/25232331", "http://www.ncbi.nlm.nih.gov/pubmed/24979569", "http://www.ncbi.nlm.nih.gov/pubmed/23226608", "http://www.ncbi.nlm.nih.gov/pubmed/24957520", "http://www.ncbi.nlm.nih.gov/pubmed/24315216" ], "ideal_answer": [ "Gradenigo's syndrome is a rare but life threatening complication of acute otitis media, which includes a classic triad of otitis media, deep facial pain and ipsilateral abducens nerve paralysis." ], "exact_answer": [ [ "otitis media" ], [ "deep facial pain" ], [ "abducens nerve paralysis" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816" ], "type": "list", "id": "56be1723ef6e39474100000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "INTRODUCTION: Gradenigo's syndrome is nowadays a rare condition characterized by a triad of otorrhea, facial pain with trigeminal nerve involvement and abducens nerve palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24957520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Gradenigo's syndrome is a rare but life threatening complication of acute otitis media (AOM), which includes a classic triad of otitis media, deep facial pain and ipsilateral abducens nerve paralysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24315216", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 416, "text": "We report a case of typical Gradenigo's syndrome, including left abducens nerve palsy, left facial pain and paresthesia in V1 and V2 distribution of trigeminal nerve caused by solitary osseous plasmacytoma of the left petrous apex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24979569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "BACKGROUND: Gradenigo's syndrome is a rare disease, which is characterized by the triad of the following conditions: suppurative otitis media, pain in the distribution of the first and the second division of trigeminal nerve, and abducens nerve palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22978305", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 884, "text": "RESULTS: It was after Gradenigo that the well-known syndrome consisting of diplopia and facial pain due to a middle ear infection was named.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23226608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Gradenigo's syndrome, the triad of suppurative otitis media, abducens nerve palsy and pain in the ophthalmic division of the trigeminal nerve, remains a rare complication of otitis media.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "In 1904, Giuseppe Gradenigo published his case series on the triad of ipsilateral abducens nerve palsy, facial pain in the trigeminal nerve distribution, and suppurative otitis media, which would subsequently be referred to as Gradenigo syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25232331", "endSection": "abstract" } ] }, { "body": "Is Wnt16b secreted in response to chemotherapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23114711", "http://www.ncbi.nlm.nih.gov/pubmed/25050785", "http://www.ncbi.nlm.nih.gov/pubmed/22863786" ], "ideal_answer": [ "Yes, WNT16B is secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation." ], "exact_answer": "yes", "type": "yesno", "id": "56e6f027a12c1fc13b000001", "snippets": [ { "offsetInBeginSection": 313, "offsetInEndSection": 514, "text": " In this study, we found WNT16B could be expressed and secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050785", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 593, "text": "In a recent article in Nature Medicine, Sun et al. show that increased expression of Wnt family member wingless-type MMTV integration site family member 16B (WNT16B) by the tumor microenvironment in response to cytotoxic damage and signals through the canonical Wnt pathway to promote tumor growth and chemotherapy resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23114711", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 591, "text": "Using a genome-wide analysis of transcriptional responses to genotoxic stress induced by cancer therapeutics, we identified a spectrum of secreted proteins derived from the tumor microenvironment that includes the Wnt family member wingless-type MMTV integration site family member 16B (WNT16B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863786", "endSection": "abstract" } ] }, { "body": "Do DNA double-strand breaks play a causal role in carcinogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11178982", "http://www.ncbi.nlm.nih.gov/pubmed/22363173", "http://www.ncbi.nlm.nih.gov/pubmed/22034884", "http://www.ncbi.nlm.nih.gov/pubmed/21281740", "http://www.ncbi.nlm.nih.gov/pubmed/23450137", "http://www.ncbi.nlm.nih.gov/pubmed/22170030", "http://www.ncbi.nlm.nih.gov/pubmed/21511815", "http://www.ncbi.nlm.nih.gov/pubmed/22899337", "http://www.ncbi.nlm.nih.gov/pubmed/16650867", "http://www.ncbi.nlm.nih.gov/pubmed/17985346", "http://www.ncbi.nlm.nih.gov/pubmed/12488587", "http://www.ncbi.nlm.nih.gov/pubmed/20663777", "http://www.ncbi.nlm.nih.gov/pubmed/17494053", "http://www.ncbi.nlm.nih.gov/pubmed/16596281", "http://www.ncbi.nlm.nih.gov/pubmed/15918908", "http://www.ncbi.nlm.nih.gov/pubmed/11285192", "http://www.ncbi.nlm.nih.gov/pubmed/23469115", "http://www.ncbi.nlm.nih.gov/pubmed/19027772", "http://www.ncbi.nlm.nih.gov/pubmed/20373286", "http://www.ncbi.nlm.nih.gov/pubmed/22366412", "http://www.ncbi.nlm.nih.gov/pubmed/23393345", "http://www.ncbi.nlm.nih.gov/pubmed/17919494", "http://www.ncbi.nlm.nih.gov/pubmed/9111196", "http://www.ncbi.nlm.nih.gov/pubmed/21421565", "http://www.ncbi.nlm.nih.gov/pubmed/22979979" ], "ideal_answer": [ "Yes. It has been demonstrated that induction of DNA double-strand breaks (DSBs) and defects in overall DSBs repair capacity can lead to an accumulation of mutations, resulting in genomic instability of cells. Given that genomic instability is the hallmark of cancer, DSBs play a causal role in carcinogenesis." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053903", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006302", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0035861" ], "type": "yesno", "id": "5162f5b6298dcd4e5100004c", "snippets": [ { "offsetInBeginSection": 127, "offsetInEndSection": 410, "text": "The DNA non-homologous end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA double-strand breaks (DSBs) induced by both exogenous and endogenous DNA-damaging agents. Defects in overall DSB repair capacity can lead to genomic instability and carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393345", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 364, "text": "The tumor suppressor breast cancer susceptibility protein 1 (BRCA1) protects our cells from genomic instability in part by facilitating the efficient repair of DNA double-strand breaks (DSBs). BRCA1 promotes the error-free repair of DSBs through homologous recombination and is also implicated in the regulation of nonhomologous end joining (NHEJ) repair fidelity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22170030", "endSection": "sections.0" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1391, "text": "The increased frequency of DSB mutagenesis and MMEJ repair in the absence of BRCA1 suggests a potential mechanism for carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22170030", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Comet assay under neutral conditions allows detection of DNA double-strand breaks (DSBs), which has consequence to genome instability and carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21281740", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Loss of p15/Ink4b accompanies tumorigenesis triggered by complex DNA double-strand breaks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20663777", "endSection": "title" }, { "offsetInBeginSection": 97, "offsetInEndSection": 341, "text": "Although DSBs are potentially carcinogenic, it is not clear whether complex DSBs that are refractory to repair are more potently tumorigenic compared with simple breaks that can be rapidly repaired, correctly or incorrectly, by mammalian cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20663777", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19027772", "endSection": "title" }, { "offsetInBeginSection": 356, "offsetInEndSection": 517, "text": "Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19027772", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17985346", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Nitric oxide and acid induce double-strand DNA breaks in Barrett's esophagus carcinogenesis via distinct mechanisms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17919494", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "DNA double-strand break repair capacity and risk of breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17494053", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "A tumorigenic role of the non-homologous end-joining (NHEJ) pathway for the repair of DNA double-strand breaks (DSBs) has been suggested by our finding of a significant association between increased breast cancer risk and a cooperative effect of single-nucleotide polymorphisms in NHEJ genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17494053", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Carcinogen-induced DNA double strand break repair in sporadic breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16650867", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 473, "text": "Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis. Prior studies have demonstrated that peripheral blood mononuclear cells (PBMC) from breast cancer patients exhibit increased numbers of DNA strand breaks after exposure to ionizing radiation, but these studies did not specifically measure DNA double strand breaks and it is not known whether chemical carcinogens produce similar effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16650867", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Abnormal DNA end-joining activity in human head and neck cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596281", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 475, "text": "In human cells, DNA double-strand breaks (DSBs) are repaired primarily by the DNA end-joining (EJ) process and thus, abnormal DNA EJ activities lead to an accumulation of mutations and/or aneuploidy, resulting in genetic instability of cells. Since genetic instability is the hallmark of cancer cells, we studied the DNA EJ activities of normal, non-malignant immortalized and malignant human epithelial cells to investigate the association between DNA EJ and carcinogenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596281", "endSection": "sections.0" }, { "offsetInBeginSection": 95, "offsetInEndSection": 485, "text": "Homologous recombination repair plays an important role in DSB repair and impairment of this repair mechanism may lead to loss of genomic integrity, which is one of the hallmarks of cancer. Recent research has shown that the tumor suppressor genes p53 and BRCA1 and -2 are involved in the proper control of homologous recombination, suggesting a role of this type of repair in human cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11178982", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "In order to study the role of DNA damage processing in the development of cutaneous squamous cell carcinoma (SCC), we assessed the ability of six keratinocyte cell lines from a multistage-tumor progression model to repair three types of DNA damage: pyrimidine dimers, oxidative DNA lesions and DNA double strand breaks (DSB).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9111196", "endSection": "sections.0" }, { "offsetInBeginSection": 1822, "offsetInEndSection": 2004, "text": "However, an acquired deficiency in repairing DNA double strand breaks can be one mechanism promoting progression towards malignancy, possibly through impairing chromosomal stability.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9111196", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Recent findings demonstrate that accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks in cells, which escaped apoptosis due to proliferative stress.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22899337", "endSection": "sections.0" }, { "offsetInBeginSection": 274, "offsetInEndSection": 420, "text": "Although DNA double-strand breaks and apoptosis may relate to arsenite-induced damage and carcinogenesis, the mechanism of action remains obscure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22366412", "endSection": "sections.0" } ] }, { "body": "Do conserved noncoding elements co-occur with matrix-attachment regions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12615002" ], "ideal_answer": [ "Yes. It is estimated that 11% of the conserved noncoding DNA consists of predicted MARs. Conversely, more than half of the predicted MARs co-occur with one or more independently identified conserved sequence blocks. An excess of conserved predicted MARs is seen in intergenic regions preceding 5' ends of genes, suggesting that these MARs are primarily involved in transcriptional control." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045170", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D036961" ], "type": "yesno", "id": "5544df2a5beec11c10000006", "snippets": [ { "offsetInBeginSection": 154, "offsetInEndSection": 1019, "text": "We hypothesized that some of these regions might be matrix-scaffold attachment regions, MARs (or S/MARs). MARs comprise one of the few classes of eukaryotic noncoding DNA with an experimentally characterized function, being involved in the attachment of chromatin to the nuclear matrix, chromatin remodeling and transcription regulation. To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments. We found that 11% of the conserved noncoding DNA consists of predicted MARs. Conversely, more than half of the predicted MARs co-occur with one or more independently identified conserved sequence blocks. An excess of conserved predicted MARs is seen in intergenic regions preceding 5' ends of genes, suggesting that these MARs are primarily involved in transcriptional control", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615002", "endSection": "title" }, { "offsetInBeginSection": 492, "offsetInEndSection": 642, "text": "To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615002", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 641, "text": "To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615002", "endSection": "abstract" } ] }, { "body": "What is the relationship between thyroid hormone and inflammatory markers in heart failure patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15259379", "http://www.ncbi.nlm.nih.gov/pubmed/12165115", "http://www.ncbi.nlm.nih.gov/pubmed/11021766", "http://www.ncbi.nlm.nih.gov/pubmed/15521205", "http://www.ncbi.nlm.nih.gov/pubmed/19926244", "http://www.ncbi.nlm.nih.gov/pubmed/16524802" ], "ideal_answer": [ "There is an inverse correlation between inflammatory markers (IL-6 and TNF alfa and PCR) and FT3 levels in patients with heart failure" ], "exact_answer": [ "There is an inverse correlation between inflammatory markers and FT3 circulating levels" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007249", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002544", "http://www.disease-ontology.org/api/metadata/DOID:9651", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143" ], "type": "factoid", "id": "53261e79600967d132000003", "snippets": [ { "offsetInBeginSection": 1530, "offsetInEndSection": 1843, "text": "Considering normal subjects, patients without and with low T3 syndrome, IL-6 and TNFalpha increased progressively from normal to patients with fT3<2 pg/ml (p<0.01 and p<0.01) while CRP only respect to the group with low T3 syndrome (p<0.01). The inflammatory markers were all inversely correlated with FT3 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19926244", "endSection": "abstract" } ] }, { "body": "Which variables are included in the SPAN-100 score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23894342", "http://www.ncbi.nlm.nih.gov/pubmed/24557701", "http://www.ncbi.nlm.nih.gov/pubmed/25194739", "http://www.ncbi.nlm.nih.gov/pubmed/25542499", "http://www.ncbi.nlm.nih.gov/pubmed/23175723", "http://www.ncbi.nlm.nih.gov/pubmed/25064957", "http://www.ncbi.nlm.nih.gov/pubmed/24798141", "http://www.ncbi.nlm.nih.gov/pubmed/24473180" ], "ideal_answer": [ "SPAN-100 score includes patient's age and NIH Stroke Scale score. SPAN-100 is used for prognostication of stroke patients." ], "exact_answer": [ [ "Age" ], [ "NIH Stroke Scale score" ] ], "type": "list", "id": "550e9d2cb305b40c5c000001", "snippets": [ { "offsetInBeginSection": 1040, "offsetInEndSection": 1240, "text": "Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI\u200a=\u200a0.175; p\u200a=\u200a0.04). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Stroke Prognostication using Age and NIH Stroke Scale: SPAN-100.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175723", "endSection": "title" }, { "offsetInBeginSection": 431, "offsetInEndSection": 584, "text": "METHODS: We created the Stroke Prognostication using Age and NIH Stroke Scale (SPAN) index by combining age in years plus NIH Stroke Scale (NIHSS) \u2265100. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175723", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1078, "text": "The SPAN-100 index is considered positive if the sum of the age and the NIH Stroke Scale (a 15-item neurological examination scale with scores ranging from 0 to 42, with higher scores indicating more severe strokes) score is greater than or equal to 100", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "The Stroke Prognostication using Age and the NIH Stroke Scale index, created by combining age in years plus a National Institutes of Health (NIH) Stroke Scale score of 100 or higher (and hereafter referred to as the SPAN-100 index), is a simple risk score for estimating clinical outcomes for patients with acute ischemic stroke (AIS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798141", "endSection": "abstract" } ] }, { "body": "Are Drosophila ultraconserved elements candidate ncRNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25618141" ], "ideal_answer": [ "Yes. Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330" ], "type": "yesno", "id": "56d1accb67f0cb3d66000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141", "endSection": "title" }, { "offsetInBeginSection": 306, "offsetInEndSection": 1403, "text": "Here, we report the discovery and characterization of UCEs from 12 sequenced Drosophila species. We identified 98 elements \u226580 bp long with very high conservation across the Drosophila phylogeny. Population genetic analyses reveal that these UCEs are not present in mutational cold spots. Instead we infer that they experience a level of selective constraint almost 10-fold higher compared with missense mutations in protein-coding sequences, which is substantially higher than that observed previously for human UCEs. About one-half of these Drosophila UCEs overlap the transcribed portion of genes, with many of those that are within coding sequences likely to correspond to sites of ADAR-dependent RNA editing. For the remaining UCEs that are in nongenic regions, we find that many are potentially capable of forming RNA secondary structures. Among ten chosen for further analysis, we discovered that the majority are transcribed in multiple tissues of Drosophila melanogaster. We conclude that Drosophila species are rich with UCEs and that many of them may correspond to novel noncoding RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate ncRNAs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25618141", "endSection": "title" } ] }, { "body": "Which genes does thyroid hormone receptor alpha1 regulate in the liver?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11222747", "http://www.ncbi.nlm.nih.gov/pubmed/19282388" ], "ideal_answer": [ "phosphoenolpyruvate-carboxykinase\"//\n\"pyruvate kinase\"//\n\"D1\", \"deiodinase 1\"//" ], "exact_answer": [ [ "phosphoenolpyruvate-carboxykinase" ], [ "pyruvate kinase" ], [ "D1", "deiodinase 1" ] ], "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008099", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005809" ], "type": "list", "id": "516c0ed3298dcd4e5100006f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "Mice expressing the mutant thyroid hormone receptor TRalpha1R384C, which has a 10-fold reduced affinity to the ligand T(3), exhibit hypermetabolism due to an overactivation of the sympathetic nervous system. To define the consequences in the liver, we analyzed hepatic metabolism and the regulation of liver genes in the mutant mice. Our results showed that hepatic phosphoenolpyruvate-carboxykinase was up-regulated and pyruvate kinase mRNA down-regulated, contrary to what observed after T(3) treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19282388", "endSection": "sections.0" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1275, "text": "Remarkably, there was an obligatory requirement for a TR, whether TRbeta or TRalpha1, for any detectable D1 expression in liver.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11222747", "endSection": "sections.0" }, { "offsetInBeginSection": 345, "offsetInEndSection": 444, "text": "Liver and kidney D1 mRNA and activity levels were reduced in TRbeta(-/-) but not TRalpha1(-/-) mice", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11222747", "endSection": "sections.0" } ] }, { "body": "What is the color of the protein Ranasmurfin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17077494", "http://www.ncbi.nlm.nih.gov/pubmed/20615601" ], "ideal_answer": [ "Ranasmurfin is a blue protein." ], "exact_answer": [ "Blue" ], "type": "factoid", "id": "56f961b3cf1c325851000003", "snippets": [ { "offsetInBeginSection": 428, "offsetInEndSection": 554, "text": "Ranasmurfin, a blue protein from a different species of frog, displays a novel structure with a unique chromophoric crosslink.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20615601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Crystallization of Ranasmurfin, a blue-coloured protein from Polypedates leucomystax.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17077494", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Ranasmurfin, a previously uncharacterized approximately 13 kDa blue protein found in the nests of the frog Polypedates leucomystax, has been purified and crystallized. The crystals are an intense blue colour ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17077494", "endSection": "abstract" } ] }, { "body": "What is the role of Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) in development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21437264", "http://www.ncbi.nlm.nih.gov/pubmed/16905130", "http://www.ncbi.nlm.nih.gov/pubmed/21116703", "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "http://www.ncbi.nlm.nih.gov/pubmed/11850401" ], "ideal_answer": [ "Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism. HPL-2 regulates the expression of germline genes, extracellular matrix components and genes involved in lipid metabolism. In addition, HPL-2 regulates the dauer developmental decision, a striking example of phenotypic plasticity in which environmental conditions determine developmental fate. Furthermore, it is required for the formation of a functional germline and for the development of the vulva by acting in an Rb-related pathway." ], "concepts": [ "http://www.biosemantics.org/jochem#4262550", "http://amigo.geneontology.org/amigo/term/GO:0032502", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017173", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029742", "http://www.uniprot.org/uniprot/HP1_DROVI", "http://www.uniprot.org/uniprot/HP1_DROME" ], "type": "summary", "id": "56b9cabbac7ad10019000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "title" }, { "offsetInBeginSection": 378, "offsetInEndSection": 834, "text": " We show that HPL-2 regulates the expression of germline genes, extracellular matrix components and genes involved in lipid metabolism. Comparison of our expression data with HPL-2 ChIP-on-chip profiles reveals that a significant number of genes up- and down-regulated in the absence of HPL-2 are bound by HPL-2. Germline genes are specifically up-regulated in hpl-2 mutants, consistent with the function of HPL-2 as a repressor of ectopic germ cell fate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1060, "text": "HPL-2 regulates the dauer developmental decision, a striking example of phenotypic plasticity in which environmental conditions determine developmental fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1546, "text": "Our results suggest that the worm HP1 homologue HPL-2 may coordinately regulate dauer diapause, longevity and lipid metabolism, three processes dependent on developmental input and environmental conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1679, "text": "Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21437264", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 652, "text": "We have specifically characterized the intranuclear positioning of in vivo fluorescence of the Caenorhabditis elegans HP1 homologue HPL-2 as a marker for heterochromatin domains in developing embryos. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21116703", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 1277, "text": "While HPL-2 functions in vulval and germline development, no function has so far been attributed to HPL-1. Here we report the characterization of an hpl-1 null allele. We show that while the absence of hpl-1 alone results in no obvious phenotype, hpl-1;hpl-2 double mutants show synthetic, temperature sensitive phenotypes including larval lethality and severe defects in the development of the somatic gonad. Furthermore, we find that hpl-1 has an unexpected role in vulval development by acting redundantly with hpl-2, but not other genes previously implicated in vulval development. Localization studies show that like HPL-2, HPL-1 is a ubiquitously expressed nuclear protein. However, HPL-1 and HPL-2 localization does not completely overlap. Our results show that HPL-1 and HPL-2 play both unique and redundant functions in post-embryonic development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16905130", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 815, "text": "We show that one of the homologues, HPL-2, is required for the formation of a functional germline and for the development of the vulva by acting in an Rb-related pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in germline and vulval development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850401", "endSection": "title" }, { "offsetInBeginSection": 649, "offsetInEndSection": 849, "text": "We have specifically characterized the intranuclear positioning of in vivo fluorescence of the Caenorhabditis elegans HP1 homologue HPL-2 as a marker for heterochromatin domains in developing embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21116703", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 813, "text": "Germline genes are specifically up-regulated in hpl-2 mutants, consistent with the function of HPL-2 as a repressor of ectopic germ cell fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "abstract" } ] }, { "body": "Does surgery for ovarian endometriomas improve fertility?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21561807", "http://www.ncbi.nlm.nih.gov/pubmed/8737616", "http://www.ncbi.nlm.nih.gov/pubmed/7202738", "http://www.ncbi.nlm.nih.gov/pubmed/22695290", "http://www.ncbi.nlm.nih.gov/pubmed/16034960", "http://www.ncbi.nlm.nih.gov/pubmed/11526777", "http://www.ncbi.nlm.nih.gov/pubmed/21764126", "http://www.ncbi.nlm.nih.gov/pubmed/21679474", "http://www.ncbi.nlm.nih.gov/pubmed/18425908", "http://www.ncbi.nlm.nih.gov/pubmed/23759693", "http://www.ncbi.nlm.nih.gov/pubmed/15136074", "http://www.ncbi.nlm.nih.gov/pubmed/24231199", "http://www.ncbi.nlm.nih.gov/pubmed/12419041", "http://www.ncbi.nlm.nih.gov/pubmed/17399914", "http://www.ncbi.nlm.nih.gov/pubmed/2943896", "http://www.ncbi.nlm.nih.gov/pubmed/23277022" ], "ideal_answer": [ "Yes, endometrioma surgery seems to improve the success rates of fertility treatment." ], "exact_answer": "yes", "type": "yesno", "id": "54f088ee94afd61504000015", "snippets": [ { "offsetInBeginSection": 1490, "offsetInEndSection": 1764, "text": "CONCLUSION: Endometriomas per se appear to be the main cause of the reduced long-term reproductive performance of the affected patients, with little or no contribution from surgery. Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231199", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 711, "text": "Amongst the 38 women desiring pregnancy after endometrioma surgery, 19 (50%) achieved a spontaneous pregnancy during the follow-up period. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231199", "endSection": "abstract" }, { "offsetInBeginSection": 1248, "offsetInEndSection": 1325, "text": "Of 33 women who wished to conceive, 67% became pregnant, spontaneously in 59%", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23759693", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1753, "text": "CONCLUSIONS: Recurrence and pregnancy rates are encouraging in that they seem comparable to the best reported results after endometrioma cystectomy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23759693", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 291, "text": "While laparoscopic excision is known to improve fertility, recurrence can cause significant ovarian damage and adverse affects on fertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23277022", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 252, "text": "Surgery is considered to play a role within the framework of the therapeutic options to cure infertile women with the disease even though its effectiveness is generally modest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764126", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 962, "text": "Randomized controlled trials showed that the excision technique is associated with a higher pregnancy rate and a lower rate of recurrence although it may determine severe injury to the ovarian reserve. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21764126", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 258, "text": "Surgical treatment is associated with a high recurrence rate and its employment for women undergoing assisted conception has recently been challenged.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21561807", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1114, "text": "Laparoscopic excision of ovarian endometrioma prior to IVF does not offer any additional benefit over expectant management. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21561807", "endSection": "abstract" }, { "offsetInBeginSection": 2521, "offsetInEndSection": 2723, "text": "For those women subsequently attempting to conceive it was also associated with a subsequent increased spontaneous pregnancy rate in women who had documented prior sub-fertility (OR 5.21 CI 2.04-13.29).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18425908", "endSection": "abstract" }, { "offsetInBeginSection": 2959, "offsetInEndSection": 3173, "text": "here is insufficient evidence to favour excisional surgery over ablative surgery with respect to the chance of pregnancy after controlled ovarian stimulation and intra-uterine insemination (OR 1.40 CI 0.47-4.15) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18425908", "endSection": "abstract" }, { "offsetInBeginSection": 1875, "offsetInEndSection": 2223, "text": "CONCLUSIONS: These findings suggest that in a context of more than one year infertility only related to endometriosis, it is reasonable to offer these patients a complete operative laparoscopic treatment of their lesions, which enables 65% of them to be pregnant within a 8.5 months post-surgical median time to pregnancy and spontaneously in 60%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17399914", "endSection": "abstract" }, { "offsetInBeginSection": 2173, "offsetInEndSection": 2632, "text": " It was also associated with a subsequent increased rate of spontaneous pregnancy women who had documented prior sub-fertility (OR 5.21 CI 2.04-13.29). AUTHORS' CONCLUSIONS: There is some evidence that excisional surgery for endometriomata provides for a more favourable outcome than drainage and ablation, with regard to the recurrence of the endometrioma, recurrence of symptoms and subsequent spontaneous pregnancy in women who were previously subfertile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034960", "endSection": "abstract" }, { "offsetInBeginSection": 58, "offsetInEndSection": 186, "text": "Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12419041", "endSection": "abstract" }, { "offsetInBeginSection": 1539, "offsetInEndSection": 1717, "text": "In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12419041", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 577, "text": "Improvement of pain symptoms occurred in 87% of the patients and fertility rate was 45%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8737616", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 609, "text": "The long-term results, especially the fertility outcome, have been promising: 12 of 20 women (60%) achieved a term pregnancy following a laparoscopic endometrioma procedure alone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2943896", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 301, "text": "Among this group, 115 patients (54%) conceived following surgery; of these conceptions, 109 resulted in a living child.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7202738", "endSection": "abstract" }, { "offsetInBeginSection": 2259, "offsetInEndSection": 2523, "text": "WIDER IMPLICATIONS OF THE FINDINGS: Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22695290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Ovarian endometriomas does not exclude fertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11526777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15136074", "endSection": "title" }, { "offsetInBeginSection": 232, "offsetInEndSection": 356, "text": "Conclusion(s): Laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15136074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22695290", "endSection": "abstract" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1430, "text": "Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679474", "endSection": "abstract" }, { "offsetInBeginSection": 1629, "offsetInEndSection": 1721, "text": "Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231199", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 828, "text": "Laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15136074", "endSection": "abstract" } ] }, { "body": "Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22407809", "http://www.ncbi.nlm.nih.gov/pubmed/22358459", "http://www.ncbi.nlm.nih.gov/pubmed/15495263", "http://www.ncbi.nlm.nih.gov/pubmed/11257471", "http://www.ncbi.nlm.nih.gov/pubmed/15564032", "http://www.ncbi.nlm.nih.gov/pubmed/16945536", "http://www.ncbi.nlm.nih.gov/pubmed/12805120", "http://www.ncbi.nlm.nih.gov/pubmed/19648653", "http://www.ncbi.nlm.nih.gov/pubmed/20012312", "http://www.ncbi.nlm.nih.gov/pubmed/11166164" ], "ideal_answer": [ "Yes, most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes.", "Yes. Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. Mutations in six genes have been reported to cause NM: Nebulin (NEB Pelin 1999), alpha-skeletal muscle actin (ACTA1 Nowak 1999), alpha-slow tropomyosin (TPM3 Laing 1995), beta-tropomyosin (TPM2 Donner 2002), slow troponin T (TNNT1 Johnston 2000) and cofilin 2 (CFL2 Agrawal 2007)." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/NEBU_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:3191", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017696", "http://www.uniprot.org/uniprot/ACTS_CYPCA", "http://www.uniprot.org/uniprot/ACTS_ORYLA", "http://www.uniprot.org/uniprot/ACTS_ATRMM", "http://www.uniprot.org/uniprot/ACTS_CARAU", "http://www.uniprot.org/uniprot/ACTS_OREMO" ], "type": "yesno", "id": "552440452c8b63434a00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions \"nemaline bodies\" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22407809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin). 20-25% of NM cases carry ACTA1 defects and these particular mutations usually induce substitutions of single residues in the actin protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22358459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 487, "text": "Nemaline myopathy (NM) is a genetically and clinically heterogenous muscle disorder, which is myopathologically characterized by nemaline bodies. Mutations in six genes have been reported to cause NM: Nebulin (NEB Pelin 1999), alpha-skeletal muscle actin (ACTA1 Nowak 1999), alpha-slow tropomyosin (TPM3 Laing 1995), beta-tropomyosin (TPM2 Donner 2002), slow troponin T (TNNT1 Johnston 2000) and cofilin 2 (CFL2 Agrawal 2007). The majority of cases are due to mutation in NEB and ACTA1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20012312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 635, "text": "Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis of nemaline myopathy difficult in some cases. Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19648653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16945536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "We report muscle MRI findings of 10 patients from 8 families with nemaline myopathy. Patients with involvement of the nebulin (NEB) gene showed a consistent pattern of selective muscle involvement corresponding to clinical severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15564032", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 719, "text": "Patients with nemaline myopathy secondary to mutations in the skeletal muscle alpha-actin (ACTA1) gene showed diffuse involvement of thigh and leg muscles with relative sparing of the gastrocnemii.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15564032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 584, "text": "Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness ranging in severity. Three major forms have been identified: actin myopathy, intranuclear rod myopathy, and nemaline myopathy. Nemaline myopathy is the most common of these myopathies and is further subdivided into seven groups according to severity, progressiveness, and age of onset. At present, five genes have been linked to congenital myopathies. These include alpha-actin (ACTA1), alpha- and beta-tropomyosin (TPM3 and TPM2), troponin T (TNNT1), and nebulin (NEB). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15495263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "Nemaline myopathy is a structural congenital myopathy which may show both autosomal dominant and autosomal recessive inheritance patterns. Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11257471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 426, "text": "Nemaline myopathy is a clinically and genetically heterogeneous condition. The clinical spectrum ranges from severe cases with antenatal or neonatal onset and early death to late onset cases with only slow progression. Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11166164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22358459", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 423, "text": "Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11166164", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 294, "text": "Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16945536", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 634, "text": "Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19648653", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 295, "text": "Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805120", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 425, "text": "Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11166164", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 360, "text": "Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11257471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16945536", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 293, "text": "Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805120", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 423, "text": "Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11166164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22358459", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 294, "text": "Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22358459", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 359, "text": "Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11257471", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 424, "text": "Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11166164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16945536", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 633, "text": "Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19648653", "endSection": "abstract" } ] }, { "body": "What are the pregnancy outcomes in rheumatoid arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23382363", "http://www.ncbi.nlm.nih.gov/pubmed/19826816", "http://www.ncbi.nlm.nih.gov/pubmed/20031371", "http://www.ncbi.nlm.nih.gov/pubmed/22176821", "http://www.ncbi.nlm.nih.gov/pubmed/16508972", "http://www.ncbi.nlm.nih.gov/pubmed/23773975", "http://www.ncbi.nlm.nih.gov/pubmed/23359233", "http://www.ncbi.nlm.nih.gov/pubmed/16649008", "http://www.ncbi.nlm.nih.gov/pubmed/20337545", "http://www.ncbi.nlm.nih.gov/pubmed/22028718", "http://www.ncbi.nlm.nih.gov/pubmed/2189302", "http://www.ncbi.nlm.nih.gov/pubmed/19406733", "http://www.ncbi.nlm.nih.gov/pubmed/20534371", "http://www.ncbi.nlm.nih.gov/pubmed/20131283" ], "ideal_answer": [ "There is increased obstetrical and neonatal morbidity. Women with RA had an increased risk of LBW, SGA babies, preeclampsia and CS compared with unaffected women.\nWomen with RA appear to have a higher age-adjusted risk of adverse outcomes of pregnancy and longer hospital stays than do pregnant women in the general population, and careful antenatal monitoring should be performed.Patients with rheumatic disease can have successful pregnancy outcomes, particularly when a collaborative approach between the rheumatologist and obstetrician is applied.\nIn general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011256" ], "type": "summary", "id": "52fb19ab2059c6d71c00005c", "snippets": [ { "offsetInBeginSection": 690, "offsetInEndSection": 861, "text": "Patients with rheumatic disease can have successful pregnancy outcomes, particularly when a collaborative approach between the rheumatologist and obstetrician is applied. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23773975", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 1444, "text": "Of 78 JIA pregnancies, 53 (68%) were delivered by either Caesarean section (n = 40, 51%) or instrumental delivery (n = 13, 17%); compared with other women, those with JIA had significantly higher rates of pre-eclampsia, postpartum haemorrhage and severe maternal morbidity. Compared with other infants, those with mothers with JIA were more likely to be born prematurely, but were not at increased risk of being small for gestational age, requiring neonatal intensive care, having a low Apgar score at 5 min or severe neonatal morbidity. CONCLUSIONS: Infants of women with JIA did not have an increased risk of adverse neonatal outcomes. Intensive obstetric care might be required during pregnancy for women with JIA given the increased risk of maternal morbidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "High rate of preterm birth in pregnancies complicated by rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359233", "endSection": "title" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1029, "text": "Women with RA may be at higher risk for preterm delivery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359233", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 1158, "text": "A significant increase in frequency and number of cesarean deliveries, besides a higher number of pregnancies with preeclampsia, were found after RA onset. Additionally, four newborns with congenital anomalies were reported after the disease onset compared to none before RA onset. CONCLUSIONS: compared to pre-RA obstetric events, a higher frequency and number of adverse outcomes was found in pregnancies that occurred after RA onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22176821", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1382, "text": "There is increased obstetrical and neonatal morbidity in Canadian women with RA or SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Most pregnancies in women with rheumatologic disease will result in the delivery of a healthy baby. Pregnancy can be particularly risky in women with active disease or on teratogenic medications,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20534371", "endSection": "abstract" }, { "offsetInBeginSection": 670, "offsetInEndSection": 765, "text": "Rheumatoid arthritis typically improves and does not have a major impact on pregnancy outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20534371", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1790, "text": "Although the sample size is small, these data do not support the notion that there is a substantial increased risk of adverse pregnancy outcomes due to leflunomide exposure among women who undergo cholestyramine elimination procedure early in pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20131283", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 1047, "text": "Nonetheless, pregnancies in most autoimmune diseases are still classified as high risk because of the potential for major complications. These complications include disease exacerbations during gestation and increased perinatal mortality and morbidity in most autoimmune diseases,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20031371", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1200, "text": "We conclude that pregnancy outcome in patients with SLE in India is worse in comparison to patients with RA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19826816", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1055, "text": "Women with RA had an increased risk of LBW, SGA babies, preeclampsia and CS compared with unaffected women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19406733", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 897, "text": "Infants of women with rheumatoid arthritis had increased risk of cesarean delivery (adjusted approximate relative risk, aRR=1.66, 95% CI (1.22, 2.26)), prematurity (aRR=1.78, 95% CI (1.21, 2.60)), and longer birth hospitalization (aRR=1.86, 95% CI (1.32, 2.60)) compared to those born to women without rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16649008", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1415, "text": "Women with SLE, RA, and pregestational DM had significantly increased rates of hypertensive disorders compared with the general obstetric population (23.2%, 11.1%, 27.4%, and 7.8%, respectively), longer hospital stays, and significantly higher risk of cesarean delivery. Although women with SLE, RA, and pregestational DM were significantly older than women in the general obstetric population, disparities in the risk of adverse outcomes of pregnancy remained statistically significant after adjustment for maternal age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16508972", "endSection": "abstract" }, { "offsetInBeginSection": 1597, "offsetInEndSection": 1823, "text": "women with SLE and RA appear to have a higher age-adjusted risk of adverse outcomes of pregnancy and longer hospital stays than do pregnant women in the general population, and careful antenatal monitoring should be performed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16508972", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1447, "text": "In this uncontrolled study we failed to demonstrate tertogenicity of MTX. However, the possibility of abortion due to MTX use remains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2189302", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 967, "text": "In general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20337545", "endSection": "abstract" } ] }, { "body": "What is DNAshape?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23703209" ], "ideal_answer": [ "DNAshape is a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data. This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies. The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations. It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist). The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach. The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/." ], "type": "summary", "id": "56c8f7445795f9a73e00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23703209", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 914, "text": "We present a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data. This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies. The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations. It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist). The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach. The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23703209", "endSection": "abstract" } ] }, { "body": "How are thyroid hormones involved in the development of diabetic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2934121", "http://www.ncbi.nlm.nih.gov/pubmed/2059900", "http://www.ncbi.nlm.nih.gov/pubmed/3181644", "http://www.ncbi.nlm.nih.gov/pubmed/2830793", "http://www.ncbi.nlm.nih.gov/pubmed/8590944", "http://www.ncbi.nlm.nih.gov/pubmed/6134470" ], "ideal_answer": [ "The diabetic state is associated with lowered T3 and T4 levels. Thyroid hormone treatment in diabetic cardiomyopathy may partially reverse cardiac dysfunction" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.biosemantics.org/jochem#4250045", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.biosemantics.org/jochem#4275389" ], "type": "summary", "id": "51751ee48ed59a060a000025", "snippets": [ { "offsetInBeginSection": 444, "offsetInEndSection": 501, "text": "Diabetic animals developed low triiodothyronine syndrome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8590944", "endSection": "sections.0" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1448, "text": "They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2059900", "endSection": "sections.0" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1728, "text": "Treatment of diabetic RVH rats with T3 (10 micrograms.kg-1.day-1) in vivo was nearly as effective as insulin therapy (10 U.kg-1.day-1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline loss", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2059900", "endSection": "sections.0" }, { "offsetInBeginSection": 163, "offsetInEndSection": 252, "text": "the diabetic state in rats is associated with lowered T3 (triiodothyronine) and T4 levels", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3181644", "endSection": "sections.0" }, { "offsetInBeginSection": 869, "offsetInEndSection": 997, "text": "Thyroid status of diabetic animals was normalized by T3 alone or in combination with myo-inositol but not by myo-inositol alone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3181644", "endSection": "sections.0" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1440, "text": "T3 treatment alone did not prevent cardiac dysfunction in diabetic rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3181644", "endSection": "sections.0" }, { "offsetInBeginSection": 455, "offsetInEndSection": 645, "text": "Untreated diabetic rats exhibited a decrease in spontaneous heart rate and myocardial cytochrome c concentrations concurrent with depressed plasma T3 values compared with untreated controls.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2830793", "endSection": "sections.0" }, { "offsetInBeginSection": 646, "offsetInEndSection": 845, "text": "T3 treatment did not improve in vitro cardiac performance (assessed as cardiac output times peak systolic pressure per gram dry heart weight) in hearts from diabetic rats perfused with glucose alone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2830793", "endSection": "sections.0" }, { "offsetInBeginSection": 846, "offsetInEndSection": 989, "text": "Addition of octanoate reversed this depression and improved cardiac function to a greater extent in treated than in untreated diabetic animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2830793", "endSection": "sections.0" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1392, "text": "As triiodothyronine (T3) treatment has been shown to normalize depression of cardiac myosin ATPase in diabetic rats", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2934121", "endSection": "sections.0" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1773, "text": "While diabetic rats treated with T3 alone did not show significant improvement of myocardial function when compared with untreated diabetics, the function of those treated with both T3 and methyl palmoxirate was not significantly different from that in control rat hearts", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2934121", "endSection": "sections.0" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1125, "text": "Although the plasma level of thyroid hormone was decreased in the diabetic rat, thyroid hormone treatment did not restore microsomal calcium transport in the diabetic animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6134470", "endSection": "sections.0" } ] }, { "body": "By which methods can we evaluate the reliability of a phylogenetic tree?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19423664", "http://www.ncbi.nlm.nih.gov/pubmed/19748458", "http://www.ncbi.nlm.nih.gov/pubmed/21940641", "http://www.ncbi.nlm.nih.gov/pubmed/20207713", "http://www.ncbi.nlm.nih.gov/pubmed/21851592", "http://www.ncbi.nlm.nih.gov/pubmed/12857639", "http://www.ncbi.nlm.nih.gov/pubmed/15008414", "http://www.ncbi.nlm.nih.gov/pubmed/22940609", "http://www.ncbi.nlm.nih.gov/pubmed/11411692", "http://www.ncbi.nlm.nih.gov/pubmed/7544864", "http://www.ncbi.nlm.nih.gov/pubmed/22289866", "http://www.ncbi.nlm.nih.gov/pubmed/21899420", "http://www.ncbi.nlm.nih.gov/pubmed/23060619" ], "ideal_answer": [ "The methods for assessing the robustness/reliability of the topology of the inferred phylogenetic trees are: the widely used bootstrap method and the jackknife method.", "In contrast to other similar software, the program FreeTree (available at http://www.natur.cuni.cz/~flegr/programs/freetree or http://ijs.sgmjournals.org/content/vol51/issue3/) can also assess the robustness of the tree topology by bootstrap, jackknife or operational taxonomic unit-jackknife analysis. (PMID: 11411692)" ], "exact_answer": [ [ "bootstrap" ], [ "jackknife" ] ], "type": "list", "id": "516ec97f298dcd4e51000087", "snippets": [ { "offsetInBeginSection": 388, "offsetInEndSection": 473, "text": "For robustness evaluation, we apply bootstrap and jackknife techniques to input data.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22940609", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "An alignment confidence score capturing robustness to guide tree uncertainty.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20207713", "endSection": "title" }, { "offsetInBeginSection": 735, "offsetInEndSection": 817, "text": "We build on the widely used bootstrap method for perturbing the phylogenetic tree.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20207713", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "SuperTRI: A new approach based on branch support analyses of multiple independent data sets for assessing reliability of phylogenetic inferences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748458", "endSection": "title" }, { "offsetInBeginSection": 645, "offsetInEndSection": 1076, "text": "To overcome these limitations, we propose a new approach, called SuperTRI, which is based on the branch support analyses of the independent data sets, and where the reliability of the nodes is assessed using three measures: the supertree Bootstrap percentage and two other values calculated from the separate analyses: the mean branch support (mean Bootstrap percentage or mean posterior probability) and the reproducibility index.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748458", "endSection": "sections.0" }, { "offsetInBeginSection": 215, "offsetInEndSection": 517, "text": "In contrast to other similar software, the program FreeTree (available at http://www.natur.cuni.cz/~flegr/programs/freetree or http://ijs.sgmjournals.org/content/vol51/issue3/) can also assess the robustness of the tree topology by bootstrap, jackknife or operational taxonomic unit-jackknife analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11411692", "endSection": "sections.0" }, { "offsetInBeginSection": 479, "offsetInEndSection": 665, "text": "Unlike any previous tool for inferring phylogenies from rearrangement data, TIBA uses novel methods of robustness estimation to provide support values for the edges in the inferred tree.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23060619", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Fast and accurate phylogenetic reconstruction from high-resolution whole-genome data and a novel robustness estimator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21899420", "endSection": "title" }, { "offsetInBeginSection": 518, "offsetInEndSection": 767, "text": "Moreover, whereas phylogenetic analyses from sequence data are deemed incomplete unless bootstrapping scores (a measure of confidence) are given for each tree edge, no equivalent to bootstrapping exists for rearrangement-based phylogenetic analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21899420", "endSection": "sections.0" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1087, "text": "We also describe a novel approach to estimate the robustness of results-an equivalent to the bootstrapping analysis used in sequence-based phylogenetic reconstruction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21899420", "endSection": "sections.0" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1510, "text": "The standard deviation also suggests the reliability level of the branch order.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15008414", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Assessment of the reliability of a given phylogenetic hypothesis is an important step in phylogenetic analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12857639", "endSection": "sections.0" }, { "offsetInBeginSection": 806, "offsetInEndSection": 936, "text": "The reliability of the phylogenetic trees was probed with the bootstrapping of 100 replicates of the original sequence alignments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7544864", "endSection": "sections.0" } ] }, { "body": "Which histone modification is primarily linked to elongating transcription?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21423663", "http://www.ncbi.nlm.nih.gov/pubmed/17046836", "http://www.ncbi.nlm.nih.gov/pubmed/23209427", "http://www.ncbi.nlm.nih.gov/pubmed/17346757", "http://www.ncbi.nlm.nih.gov/pubmed/17510366", "http://www.ncbi.nlm.nih.gov/pubmed/12667453", "http://www.ncbi.nlm.nih.gov/pubmed/22184065", "http://www.ncbi.nlm.nih.gov/pubmed/16503129" ], "ideal_answer": [ "Similarly, H3K36 trimethylation, a mark associated with transcription elongation, was specifically increased at the HD locus in the striatum and not in the cerebellum. Recent studies reviewed here demonstrate that histone deacetylation on the body of a transcribed gene is regulated via Set2-mediated methylation of histone H3-K36." ], "exact_answer": [ "H3K36me3", "H3K36 trimethylation" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.biosemantics.org/jochem#4278518", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006354" ], "type": "factoid", "id": "53372ba3d6d3ac6a34000058", "snippets": [ { "offsetInBeginSection": 1492, "offsetInEndSection": 1659, "text": "Similarly, H3K36 trimethylation, a mark associated with transcription elongation, was specifically increased at the HD locus in the striatum and not in the cerebellum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23209427", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 649, "text": "y expressing Myc protein fused with the estrogen receptor (Myc-ER) in fibroblasts, we observed that Myc, binding to the regulatory elements of Suz12, Ezh2, and Eed, induces the acetylation of histones H3 and H4 and the recruitment of elongating RNA polymerase II at their promoters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22184065", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 910, "text": "A basal level of JIL-1 binding can be defined that correlates best with the methylation of histone H3 at lysine 36, a mark that is placed co-transcriptionally", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21423663", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 329, "text": "RNA polymerase II signals for deacetylation through the methylation of histone H3 lysine 36 (H3K36), which provides the recruitment signal for the Rpd3S histone deacetylase complex (HDAC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17510366", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 868, "text": "Recent studies reviewed here demonstrate that histone deacetylation on the body of a transcribed gene is regulated via Set2-mediated methylation of histone H3-K36", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346757", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 114, "text": "H3K56 acetylation: a chromatin mark associated with the elongating RNA polymerase II", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046836", "endSection": "title" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1164, "text": "Furthermore, Rtt109 and H3K56 acetylation appear to correlate with actively transcribed genes and associate with the elongating form of polymerase II in yeast", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046836", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 371, "text": "In addition to coordinating the processing of the nascent transcript, elongating RNA polymerase II recruits histone methyltransferases to methylate lysines 4 and 36 of histone H3 in nucleosomes in the body of actively transcribed genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16503129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Set1, the yeast histone H3-lysine 4 (H3-K4) methylase, is recruited by the Pol II elongation machinery to a highly localized domain at the 5' portion of active mRNA coding regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12667453", "endSection": "abstract" } ] }, { "body": "Could RG7112 be used as cancer therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "http://www.ncbi.nlm.nih.gov/pubmed/24812409", "http://www.ncbi.nlm.nih.gov/pubmed/23084521", "http://www.ncbi.nlm.nih.gov/pubmed/24579771", "http://www.ncbi.nlm.nih.gov/pubmed/21391905", "http://www.ncbi.nlm.nih.gov/pubmed/22753001" ], "ideal_answer": [ "Yes, RG7112 has shown promising results in early phases of trials in cancer patients." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "yesno", "id": "56ed0a372ac5ed1459000006", "snippets": [ { "offsetInBeginSection": 249, "offsetInEndSection": 368, "text": "RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1518, "text": "Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 973, "text": "On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21391905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "title" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1150, "text": "On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21391905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 991, "text": "In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 909, "text": "Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 564, "text": "RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 780, "text": "Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 972, "text": "On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21391905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "title" }, { "offsetInBeginSection": 615, "offsetInEndSection": 805, "text": "In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 370, "text": "RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 384, "text": "BACKGROUND: RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 782, "text": "Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23084521", "endSection": "title" }, { "offsetInBeginSection": 189, "offsetInEndSection": 384, "text": "RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 248, "text": "Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 865, "text": "Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 showed potent antitumor activity against a panel of solid tumor cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 782, "text": "A crystal structure of the RG7112-MDM2 complex revealed that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 807, "text": "RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 524, "text": "RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 \u00b5M).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 369, "text": "Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy. RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 810, "text": "In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 615, "text": "Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900694", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 524, "text": "RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 \u00b5M).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1519, "text": "Notably, RG7112 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400593", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1642, "text": "RG7112 induced tumor regressions in solid tumors from different histotype panels, and exhibited consistent high-level activity against ALL xenografts. This high level of activity supports prioritization of RG7112 for further evaluation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753001", "endSection": "abstract" } ] }, { "body": "Which interleukin is blocked by Siltuximab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21321981", "http://www.ncbi.nlm.nih.gov/pubmed/25042199", "http://www.ncbi.nlm.nih.gov/pubmed/21211286", "http://www.ncbi.nlm.nih.gov/pubmed/20699329", "http://www.ncbi.nlm.nih.gov/pubmed/25784388", "http://www.ncbi.nlm.nih.gov/pubmed/26392750", "http://www.ncbi.nlm.nih.gov/pubmed/25294016", "http://www.ncbi.nlm.nih.gov/pubmed/23432640", "http://www.ncbi.nlm.nih.gov/pubmed/23913484", "http://www.ncbi.nlm.nih.gov/pubmed/25655379", "http://www.ncbi.nlm.nih.gov/pubmed/20808314", "http://www.ncbi.nlm.nih.gov/pubmed/21795409", "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "http://www.ncbi.nlm.nih.gov/pubmed/20179212", "http://www.ncbi.nlm.nih.gov/pubmed/21241278", "http://www.ncbi.nlm.nih.gov/pubmed/24922005", "http://www.ncbi.nlm.nih.gov/pubmed/22828917", "http://www.ncbi.nlm.nih.gov/pubmed/21216930" ], "ideal_answer": [ "Siltuximab is a monoclonal antibody that binds to interleukin-6 with high affinity and specificity." ], "exact_answer": [ "interleukin-6" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007378", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018123" ], "type": "factoid", "id": "56c1f02aef6e39474100004b", "snippets": [ { "offsetInBeginSection": 510, "offsetInEndSection": 683, "text": "This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26392750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Siltuximab, a chimeric monoclonal antibody with high affinity and specificity for interleukin-6, has been shown to enhance anti-multiple myeloma activity of bortezomib and corticosteroid in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25655379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294016", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "We compared the safety and efficacy of siltuximab (S), an anti-interleukin-6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294016", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1757, "text": "Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "PURPOSE: Siltuximab is a monoclonal antibody that binds to interleukin (IL)-6 with high affinity and specificity; C-reactive protein (CRP) is an acute-phase protein induced by IL-6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25784388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21241278", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Antitumor efficacy of the anti-interleukin-6 (IL-6) antibody siltuximab in mouse xenograft models of lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24922005", "endSection": "title" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1147, "text": "An interleukin-6 neutralizing antibody, siltuximab (CNTO 328) could inhibit STAT3 tyrosine phosphorylation in a cell-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21216930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Pharmacokinetic and pharmacodynamic modeling of an anti-interleukin-6 chimeric monoclonal antibody (siltuximab) in patients with metastatic renal cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20179212", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21321981", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "A phase 1 study of a chimeric monoclonal antibody against interleukin-6, siltuximab, combined with docetaxel in patients with metastatic castration-resistant prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828917", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "[Effects of siltuximab on the interleukin-6/Stat3 signaling pathway in ovarian cancer].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211286", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Siltuximab is a chimeric, anti-interleukin-6 monoclonal antibody with potential therapeutic benefit in castration-resistant prostate cancer (CRPC) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23432640", "endSection": "title" }, { "offsetInBeginSection": 221, "offsetInEndSection": 388, "text": "We assessed the safety and efficacy of siltuximab-a chimeric monoclonal antibody against interleukin 6-in HIV-negative patients with multicentric Castleman's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25042199", "endSection": "abstract" }, { "offsetInBeginSection": 2653, "offsetInEndSection": 2763, "text": "CONCLUSIONS: These results demonstrated that siltuximab effectively block the IL-6 signaling pathways, which. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211286", "endSection": "abstract" }, { "offsetInBeginSection": 1622, "offsetInEndSection": 1750, "text": "CONCLUSIONS: These results show that siltuximab effectively block the IL-6 signaling pathways and IL-6-induced gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20699329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20808314", "endSection": "title" }, { "offsetInBeginSection": 140, "offsetInEndSection": 255, "text": "Siltuximab is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "To study the effects of siltuximab on the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) signaling pathway in ovarian epithelial carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211286", "endSection": "abstract" }, { "offsetInBeginSection": 2631, "offsetInEndSection": 2720, "text": "These results demonstrated that siltuximab effectively block the IL-6 signaling pathways,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211286", "endSection": "abstract" }, { "offsetInBeginSection": 1586, "offsetInEndSection": 1701, "text": "These results show that siltuximab effectively block the IL-6 signaling pathways and IL-6-induced gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20699329", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 835, "text": "The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 371, "text": " Siltuximab is a chimeric, anti-interleukin-6 monoclonal antibody with potential therapeutic benefit in castration-resistant prostate cancer (CRPC) patients. We assessed the safety and tolerability of siltuximab in combination with docetaxel, the pharmacokinetics of docetaxel alone and with siltuximab, and the efficacy and pharmacodynamics of siltuximab plus docetaxel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828917", "endSection": "abstract" }, { "offsetInBeginSection": 2631, "offsetInEndSection": 2727, "text": "These results demonstrated that siltuximab effectively block the IL-6 signaling pathways, which.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Siltuximab is a chimeric, anti-interleukin-6 monoclonal antibody with potential therapeutic benefit in castration-resistant prostate cancer (CRPC) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease..", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "endSection": "title" }, { "offsetInBeginSection": 515, "offsetInEndSection": 789, "text": "Treatment of ovarian cancer cells with siltuximab reduced constitutive cytokine and chemokine production and also inhibited IL-6 signaling, tumor growth, the tumor-associated macrophage infiltrate and angiogenesis in IL-6-producing intraperitoneal ovarian cancer xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795409", "endSection": "abstract" } ] }, { "body": "ROSIER scale is used for which disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24072006", "http://www.ncbi.nlm.nih.gov/pubmed/21354569", "http://www.ncbi.nlm.nih.gov/pubmed/22014183", "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "http://www.ncbi.nlm.nih.gov/pubmed/18584275", "http://www.ncbi.nlm.nih.gov/pubmed/24850487", "http://www.ncbi.nlm.nih.gov/pubmed/22919191", "http://www.ncbi.nlm.nih.gov/pubmed/21402744", "http://www.ncbi.nlm.nih.gov/pubmed/25343496" ], "ideal_answer": [ "ROSIER (Recognition of Stroke in the Emergency Room) scale was developed as a stroke recognition tool on suspected patients in the prehospital setting." ], "exact_answer": [ "stroke" ], "type": "factoid", "id": "551fd9c06b348bb82c000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Validation of the use of the ROSIER scale in prehospital assessment of stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22919191", "endSection": "title" }, { "offsetInBeginSection": 176, "offsetInEndSection": 390, "text": "MATERIALS AND METHODS: Compared with the Cincinnati Prehospital Stroke Scale (CPSS), emergency physicians prospectively used the ROSIER as a stroke recognition tool on suspected patients in the prehospital setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22919191", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1831, "text": "CONCLUSIONS: The ROSIER is a sensitive and specific stroke recognition tool for health providers' use among Chinese patients in the prehospital setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22919191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Can the FAST and ROSIER adult stroke recognition tools be applied to confirmed childhood arterial ischemic stroke?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22014183", "endSection": "title" }, { "offsetInBeginSection": 648, "offsetInEndSection": 853, "text": " Two adult stroke recognition tools; ROSIER (Recognition of Stroke in the Emergency Room) and FAST (Face Arm Speech Test) scales were applied retrospectively to all patients to determine test sensitivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22014183", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 487, "text": " DIAGNOSTIC SCALES: The results of an assessment with the Recognition of Stroke in the Emergency Room (ROSIER) scale, the Face Arm Speech Test (FAST) scale and the diagnosis of definite or probable stroke by an emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21402744", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1471, "text": "CONCLUSIONS: The simpler FAST scale could replace the more complex ROSIER for the initial assessment of patients with suspected acute stroke in the emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21402744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "title" }, { "offsetInBeginSection": 208, "offsetInEndSection": 348, "text": "We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 2020, "offsetInEndSection": 2143, "text": "INTERPRETATION: The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 465, "text": "DIAGNOSTIC SCALES: The results of an assessment with the Recognition of Stroke in the Emergency Room (ROSIER) scale, the Face Arm Speech Test (FAST) scale and the diagnosis of definite or probable stroke by an emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21402744", "endSection": "abstract" }, { "offsetInBeginSection": 1868, "offsetInEndSection": 1974, "text": "The ROSIER scale had greater sensitivity than existing stroke recognition instruments in this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1600, "text": "If the ROSIER scale is to be clinically useful in Chinese suspected stroke patients, it requires further refinement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25343496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Evaluation of the Recognition of Stroke in the Emergency Room (ROSIER) scale in Chinese patients in Hong Kong.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25343496", "endSection": "title" }, { "offsetInBeginSection": 1973, "offsetInEndSection": 2080, "text": "The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 334, "text": "We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The simpler FAST scale could replace the more complex ROSIER for the initial assessment of patients with suspected acute stroke in the emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21402744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 468, "text": "DIAGNOSTIC SCALES: The results of an assessment with the Recognition of Stroke in the Emergency Room (ROSIER) scale, the Face Arm Speech Test (FAST) scale and the diagnosis of definite or probable stroke by an emergency department", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21402744", "endSection": "abstract" }, { "offsetInBeginSection": 1885, "offsetInEndSection": 1990, "text": "The ROSIER scale had greater sensitivity than existing stroke recognition instruments in this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 1992, "offsetInEndSection": 2098, "text": "The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 336, "text": "We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "To determine the utility of the Recognition of Stroke in the Emergency Room (ROSIER) scale as a stroke recognition tool among Chinese patients in the prehospital setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22919191", "endSection": "abstract" } ] }, { "body": "How histone deacetylation causes transcriptional gene silencing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20053684", "http://www.ncbi.nlm.nih.gov/pubmed/21976679", "http://www.ncbi.nlm.nih.gov/pubmed/21913088", "http://www.ncbi.nlm.nih.gov/pubmed/22555315", "http://www.ncbi.nlm.nih.gov/pubmed/19259094", "http://www.ncbi.nlm.nih.gov/pubmed/20516197", "http://www.ncbi.nlm.nih.gov/pubmed/22689577", "http://www.ncbi.nlm.nih.gov/pubmed/21763693", "http://www.ncbi.nlm.nih.gov/pubmed/21186298", "http://www.ncbi.nlm.nih.gov/pubmed/22990449", "http://www.ncbi.nlm.nih.gov/pubmed/22184063", "http://www.ncbi.nlm.nih.gov/pubmed/22865229", "http://www.ncbi.nlm.nih.gov/pubmed/22991226", "http://www.ncbi.nlm.nih.gov/pubmed/23114751", "http://www.ncbi.nlm.nih.gov/pubmed/22929011", "http://www.ncbi.nlm.nih.gov/pubmed/22955275", "http://www.ncbi.nlm.nih.gov/pubmed/22266186", "http://www.ncbi.nlm.nih.gov/pubmed/22947425", "http://www.ncbi.nlm.nih.gov/pubmed/22042362", "http://www.ncbi.nlm.nih.gov/pubmed/23140481", "http://www.ncbi.nlm.nih.gov/pubmed/15172996", "http://www.ncbi.nlm.nih.gov/pubmed/21211723", "http://www.ncbi.nlm.nih.gov/pubmed/21130077", "http://www.ncbi.nlm.nih.gov/pubmed/22117026", "http://www.ncbi.nlm.nih.gov/pubmed/18683042", "http://www.ncbi.nlm.nih.gov/pubmed/22956542", "http://www.ncbi.nlm.nih.gov/pubmed/22347433", "http://www.ncbi.nlm.nih.gov/pubmed/21926091", "http://www.ncbi.nlm.nih.gov/pubmed/23104973", "http://www.ncbi.nlm.nih.gov/pubmed/20504333", "http://www.ncbi.nlm.nih.gov/pubmed/11134508", "http://www.ncbi.nlm.nih.gov/pubmed/22080921", "http://www.ncbi.nlm.nih.gov/pubmed/22147512", "http://www.ncbi.nlm.nih.gov/pubmed/22542455", "http://www.ncbi.nlm.nih.gov/pubmed/23324470", "http://www.ncbi.nlm.nih.gov/pubmed/22638581", "http://www.ncbi.nlm.nih.gov/pubmed/20811718", "http://www.ncbi.nlm.nih.gov/pubmed/21811564", "http://www.ncbi.nlm.nih.gov/pubmed/21953612", "http://www.ncbi.nlm.nih.gov/pubmed/22222205", "http://www.ncbi.nlm.nih.gov/pubmed/22722849", "http://www.ncbi.nlm.nih.gov/pubmed/22438583", "http://www.ncbi.nlm.nih.gov/pubmed/21710206", "http://www.ncbi.nlm.nih.gov/pubmed/22156375", "http://www.ncbi.nlm.nih.gov/pubmed/22684523", "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "http://www.ncbi.nlm.nih.gov/pubmed/23029547", "http://www.ncbi.nlm.nih.gov/pubmed/21947346", "http://www.ncbi.nlm.nih.gov/pubmed/23382858", "http://www.ncbi.nlm.nih.gov/pubmed/22841502", "http://www.ncbi.nlm.nih.gov/pubmed/23408190", "http://www.ncbi.nlm.nih.gov/pubmed/22622000", "http://www.ncbi.nlm.nih.gov/pubmed/19745053", "http://www.ncbi.nlm.nih.gov/pubmed/22142826", "http://www.ncbi.nlm.nih.gov/pubmed/21325281", "http://www.ncbi.nlm.nih.gov/pubmed/22064865", "http://www.ncbi.nlm.nih.gov/pubmed/22422618", "http://www.ncbi.nlm.nih.gov/pubmed/22763818", "http://www.ncbi.nlm.nih.gov/pubmed/22472323", "http://www.ncbi.nlm.nih.gov/pubmed/22701735", "http://www.ncbi.nlm.nih.gov/pubmed/21947282", "http://www.ncbi.nlm.nih.gov/pubmed/23312906", "http://www.ncbi.nlm.nih.gov/pubmed/22641068", "http://www.ncbi.nlm.nih.gov/pubmed/23226217", "http://www.ncbi.nlm.nih.gov/pubmed/22393235", "http://www.ncbi.nlm.nih.gov/pubmed/23479617", "http://www.ncbi.nlm.nih.gov/pubmed/22102827", "http://www.ncbi.nlm.nih.gov/pubmed/22959268", "http://www.ncbi.nlm.nih.gov/pubmed/19782027", "http://www.ncbi.nlm.nih.gov/pubmed/23271976", "http://www.ncbi.nlm.nih.gov/pubmed/22504884", "http://www.ncbi.nlm.nih.gov/pubmed/21622623", "http://www.ncbi.nlm.nih.gov/pubmed/22570737", "http://www.ncbi.nlm.nih.gov/pubmed/22730529", "http://www.ncbi.nlm.nih.gov/pubmed/21706058", "http://www.ncbi.nlm.nih.gov/pubmed/18632628", "http://www.ncbi.nlm.nih.gov/pubmed/22577027" ], "ideal_answer": [ "Histone deacetylation, catalyzed by the histone deacetylase (HDAC) enzymes, is an epigenetic modification. Histone deacetylation leads to the formation of a condensed and transcriptionally repressive chromatin structure which inhibits gene transcription. " ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016575", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006342", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "summary", "id": "515dbb3b298dcd4e51000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 497, "text": "Lysine acetylation of histones is one of the major epigenetic regulators of chromatin conformation and gene expression. The dynamic nature of histone acetylation is determined by the counterbalancing activity of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Acetylation of histones is generally associated with open and transcriptionally active chromatin, whereas the activity of HDACs leads to histone deacetylation, condensation of chromatin, and inhibition of transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913088", "endSection": "sections.0" }, { "offsetInBeginSection": 599, "offsetInEndSection": 861, "text": "Abnormal activity of HDACs has been implicated in tumorigenesis and therefore considerable effort has been put into the development of HDAC inhibitors as a means of modifying histone acetylation status and reexpressing aberrantly silenced tumor suppressor genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913088", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "Histone acetylation and deacetylation play essential roles in eukaryotic gene regulation. Reversible modifications of core histones are catalyzed by two intrinsic enzymes, histone acetyltransferase and histone deacetylase (HD). In general, histone deacetylation is related to transcriptional gene silencing, whereas acetylation correlates with gene activation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11134508", "endSection": "sections.0" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1045, "text": "The reversible nature of deregulated chromatin structure by DNA methylation and histone deacetylation inhibitors, leading to re-expression of tumor suppressor genes, makes chromatin-remodeling pathways as promising therapeutic targets.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23114751", "endSection": "sections.0" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1392, "text": "Furthermore, the histone deacetylase inhibitor, trichostatin A (TSA), recovered the expression and function of NEO1 in the silenced lines, suggesting that histone deacetylation is essential for the direct suppression of target genes by DNAi.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990449", "endSection": "sections.0" }, { "offsetInBeginSection": 169, "offsetInEndSection": 558, "text": "We had previously shown that in anergic CD4(+) T cells, Ikaros participates in the transcriptional repression of the Il2 gene by recruiting histone deacetylases that cause core histone deacetylation at the Il2 promoter. Here we show that deacetylation at the Il2 promoter is the initial step in a process that leads to the stable silencing of the Il2 gene transcription in anergic T cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22684523", "endSection": "sections.0" }, { "offsetInBeginSection": 831, "offsetInEndSection": 986, "text": "We demonstrate that HP1 forms distinct DNA methylation and histone deacetylation complexes that work in parallel to assemble silent chromatin in N. crassa.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504884", "endSection": "sections.0" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1704, "text": "These results indicated that histone deacetylation is a silencing mechanism for GATA4 expression in AFP-producing gastric cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22472323", "endSection": "sections.0" }, { "offsetInBeginSection": 146, "offsetInEndSection": 290, "text": "We found that histone deacetylase 1 (HDAC1) increases the expression levels of mature miRNAs despite repressing the transcription of host genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22222205", "endSection": "sections.0" }, { "offsetInBeginSection": 564, "offsetInEndSection": 668, "text": "Promoter methylation and histone deacetylation were studied as possible mechanisms for klotho silencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22042362", "endSection": "sections.0" }, { "offsetInBeginSection": 1450, "offsetInEndSection": 1645, "text": "Taken together, these data indicate loss of klotho expression as an early event in breast cancer development, and suggest a role for DNA methylation and histone deacetylation in klotho silencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22042362", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "DNA methylation and histone acetylation/deacetylation are distinct biochemical processes that control gene expression. While DNA methylation is a common epigenetic signal that inhibits gene transcription, histone deacetylation similarly represses transcription but can be both an epigenetic and nonepigenetic phenomenon", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947282", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "DNA methylation and histone acetylation/deacetylation are distinct biochemical processes that control gene expression. While DNA methylation is a common epigenetic signal that inhibits gene transcription, histone deacetylation similarly represses transcription but can be both an epigenetic and nonepigenetic phenomenon.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947282", "endSection": "sections.0" }, { "offsetInBeginSection": 1497, "offsetInEndSection": 1724, "text": "Because DNA hypermethylation-based silencing may couple with and depend on histone deacetylation, our study suggests that endogenous HDAC inhibition by maspin may prevent pathologic gene silencing in prostate tumor progression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21622623", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21325281", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Heterochromatin impacts various nuclear processes by providing a recruiting platform for diverse chromosomal proteins. In fission yeast, HP1 proteins Chp2 and Swi6, which bind to methylated histone H3 lysine 9, associate with SHREC (Snf2/HDAC repressor complex) and Clr6 histone deacetylases (HDACs) involved in heterochromatic silencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211723", "endSection": "sections.0" }, { "offsetInBeginSection": 836, "offsetInEndSection": 1180, "text": "We established that the silencing of these genes in UVB-exposed epidermis and UVB-induced skin tumors is associated with a network of epigenetic modifications, including hypoacetylation of histone H3 and H4 and increased histone deacetylation, as well as recruitment of methyl-binding proteins, including MeCP2 and MBD1, to the methylated CpGs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21186298", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Histone deacetylation directs DNA methylation in survivin gene silencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21130077", "endSection": "title" }, { "offsetInBeginSection": 624, "offsetInEndSection": 787, "text": "Next, we investigated the roles of histone acetylation and DNA methylation in survivin silencing after blockade of histone deacetylation with Trichostatin A (TSA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21130077", "endSection": "sections.0" }, { "offsetInBeginSection": 1322, "offsetInEndSection": 1474, "text": "The results showed that histone deacetylation blocked by TSA reversed the increasing effect of histone deacetylation on the expression of survivin mRNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21130077", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Aberrant hypermethylation at CpG sites within the CDKN2A gene is associated with silencing and has been proposed as a target for reactivation using both DNA methylation and histone deacetylation inhibitors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811718", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Mechanisms of HDA6-mediated rRNA gene silencing: suppression of intergenic Pol II transcription and differential effects on maintenance versus siRNA-directed cytosine methylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20516197", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The Arabidopsis histone deacetylase HDA6 is required to silence transgenes, transposons, and ribosomal RNA (rRNA) genes subjected to nucleolar dominance in genetic hybrids.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20516197", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Distinct and temporal roles of nucleosomal remodeling and histone deacetylation in the repression of the hTERT gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20053684", "endSection": "title" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1478, "text": "Surprisingly, inhibition of histone deacetylation at the hTERT promoter did not prevent hTERT repression or nucleosomal deposition, indicating that nucleosomal deposition at the core promoter, but not histone deacetylation, was the cause of transcriptional repression. Our data also suggested that succeeding nucleosomal remodeling and histone deacetylation worked in parallel to establish the stable repressive status of hTERT gene in human somatic cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20053684", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Reconstitution of heterochromatin-dependent transcriptional gene silencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19782027", "endSection": "title" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1108, "text": "Silencing requires all three Sir proteins, even with fully deacetylated chromatin, and involves the specific association of Sir3 with deacetylated H4K16. These results define a minimal set of components that mediate heterochromatic gene silencing and demonstrate distinct contributions for histone deacetylation and nucleosome binding in the silencing mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19782027", "endSection": "sections.0" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1107, "text": "Silencing requires all three Sir proteins, even with fully deacetylated chromatin, and involves the specific association of Sir3 with deacetylated H4K16. These results define a minimal set of components that mediate heterochromatic gene silencing and demonstrate distinct contributions for histone deacetylation and nucleosome binding in the silencing mechanism", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19782027", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Inhibition of histone deacetylase suppresses EGF signaling pathways by destabilizing EGFR mRNA in ER-negative human breast cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18683042", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 387, "text": "Our previous studies demonstrate that histone deacetylation plays a key role in ER gene silencing, and ER expression can be restored with histone deacetylase (HDAC) inhibitors in ER-negative human breast cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18683042", "endSection": "sections.0" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1056, "text": "This chromatin pattern, and particularly H3K4me2 levels, crisply separates DNA-hypermethylated genes from those where histone deacetylation is responsible for transcriptional silencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18632628", "endSection": "sections.0" }, { "offsetInBeginSection": 761, "offsetInEndSection": 894, "text": "Loss of gene expression is not due to structural mutations, but to regulatory changes including epigenetic deacetylation of histones.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23479617", "endSection": "sections.0" }, { "offsetInBeginSection": 828, "offsetInEndSection": 998, "text": "We found that these PERV families are differentially up- or downregulated upon chemical inhibition of DNA methylation and histone deacetylation in cultured porcine cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23324470", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The class IIa histone deacetylases (HDACs) act as transcriptional repressors by altering chromatin structure through histone deacetylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22991226", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The Set3 histone deacetylase complex (Set3C) binds histone H3 dimethylated at lysine 4 (H3K4me2) to mediate deacetylation of histones in 5'-transcribed regions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22959268", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Core histone modifications play an important role in chromatin remodeling and transcriptional regulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956542", "endSection": "sections.0" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1236, "text": "These results demonstrate that the acetylation/deacetylation balance strongly influences the expression of arginase-1, a gene of alternative activation of macrophages.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22865229", "endSection": "sections.0" }, { "offsetInBeginSection": 210, "offsetInEndSection": 339, "text": "MTA1 acts as part of a nucleosome remodelling and histone deacetylation complex, which is involved in transcriptional regulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841502", "endSection": "sections.0" }, { "offsetInBeginSection": 553, "offsetInEndSection": 741, "text": "The ectopic expression of ThPOK resulted in increased recruitment of histone deacetylases at Cd8 loci; the enhanced deacetylation of Cd8 genes eventually led to impaired Cd8 transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22730529", "endSection": "sections.0" }, { "offsetInBeginSection": 213, "offsetInEndSection": 381, "text": "Sirt-1, a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, has been linked to transcriptional silencing and appears to play a key role in inflammation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22689577", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "OBJECTIVE: Histone deacetylation regulates chromatin remodeling and transcriptional down-regulation of specific genomic regions; it is altered in many types of cancer cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22641068", "endSection": "sections.0" }, { "offsetInBeginSection": 183, "offsetInEndSection": 392, "text": "Histone acetylations affect the regulation of gene transcription, and the loss of learning induced deacetylation at specific histone sites may represent biomarkers for memory loss and Alzheimer's disease (AD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577027", "endSection": "sections.0" }, { "offsetInBeginSection": 1173, "offsetInEndSection": 1403, "text": "Increasing chromatin accessibility via inhibition of histone deacetylation or DNA methylation lowered the induction threshold, demonstrating that chromatin accessibility sets the level of RelA required to activate gene expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22555315", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The NAD-dependent histone deacetylase Sirt1 antagonizes p53 transcriptional activity to regulate cell-cycle progression and apoptosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22542455", "endSection": "sections.0" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1197, "text": "These studies reveal a new mechanism by which acetyltransferase activity induces gene expression through targeted destruction of a transcriptional repressor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438583", "endSection": "sections.0" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1042, "text": "Further studies indicated that GR recruited histone deacetylase 1 to the Runx2 P2 promoter which then mediated the deacetylation of histone H4 and down-regulated Runx2 expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22422618", "endSection": "sections.0" }, { "offsetInBeginSection": 296, "offsetInEndSection": 426, "text": "RUNX2 cofactors such as histone deacetylases (HDACs) play a key role in chromatin remodeling and regulation of gene transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22393235", "endSection": "sections.0" }, { "offsetInBeginSection": 435, "offsetInEndSection": 723, "text": "In some cell lines latently infected with EBV, an HDAC inhibitor alone can induce BZLF1 transcription, while the treatment does not enhance expression in other cell lines, such as B95-8 or Raji cells, suggesting unknown suppressive mechanisms besides histone deacetylation in those cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "endSection": "sections.0" }, { "offsetInBeginSection": 489, "offsetInEndSection": 622, "text": "Furthermore, the deacetylation of p53 by EWS-Fli1 suppressed its transcriptional activity and enhanced mdm2-mediated p53 degradation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266186", "endSection": "sections.0" }, { "offsetInBeginSection": 528, "offsetInEndSection": 722, "text": "This finding suggests that HDACs have two arms for gene silencing: transcriptional repression by promoter histone deacetylation and post-transcriptional inhibition by increasing miRNA abundance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22222205", "endSection": "sections.0" }, { "offsetInBeginSection": 490, "offsetInEndSection": 626, "text": "Promoter-localized deacetylation of H3 tails is a prerequisite for VprBP to tether and act as a bona fide inhibitor at p53 target genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22184063", "endSection": "sections.0" }, { "offsetInBeginSection": 1684, "offsetInEndSection": 1825, "text": "CONCLUSIONS: These findings imply an important role for histone deacetylation in the downregulation of E-cadherin in human pancreatic cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147512", "endSection": "sections.0" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1511, "text": "Inhibition of transcription results from the release of p300 coactivator from NF-\u03baB target gene promoters and subsequent histone deacetylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22142826", "endSection": "sections.0" }, { "offsetInBeginSection": 540, "offsetInEndSection": 823, "text": "In fungi in general, gene expression is often partially controlled at the chromatin level in secondary metabolism; when this is the case, the deacetylation and acetylation (and other posttranslational modifications) of histones are usually crucial in the regulation of transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22117026", "endSection": "sections.0" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1348, "text": "For the first time, we provide direct evidence that CREM\u03b1 mediates silencing of the IL2 gene in SLE T cells though histone deacetylation and CpG-DNA methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21976679", "endSection": "sections.0" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1069, "text": "The downregulation of CD43 mRNA is caused by p53-dependent transrepression, at least in part, via a histone deacetylation mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947346", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "DNA methylation and histone acetylation/deacetylation are distinct biochemical processes that control gene expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947282", "endSection": "sections.0" }, { "offsetInBeginSection": 278, "offsetInEndSection": 497, "text": "Acetylation of histones is generally associated with open and transcriptionally active chromatin, whereas the activity of HDACs leads to histone deacetylation, condensation of chromatin, and inhibition of transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913088", "endSection": "sections.0" }, { "offsetInBeginSection": 661, "offsetInEndSection": 810, "text": "This study demonstrates that a mutual cross-talk mechanism exists between histone chaperones and histone deacetylation in transcriptional regulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21763693", "endSection": "sections.0" }, { "offsetInBeginSection": 325, "offsetInEndSection": 631, "text": "FVE is a homologue of the mammalian retinoblastoma-associated protein (RbAp), one component of a histone deacetylase (HDAC) complex involved in transcriptional repression, and has been shown to be involved in the deacetylation of the FLOWERING LOCUS C (FLC) chromatin encoding for a repressor of flowering.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21710206", "endSection": "sections.0" }, { "offsetInBeginSection": 539, "offsetInEndSection": 707, "text": "Thus, our data illustrate the orchestration of a sequential epigenetic mechanism including the histone deacetylation and methylation, and the DNA methylation processes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312906", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Histone deacetylases (HDACs) mediate histone deacetylation and act in concert with histone acetyltransferases to regulate dynamic and reversible histone acetylation which modifies chromatin structure and function, affects gene transcription, thus, controlling multiple cellular processes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23408190", "endSection": "sections.0" }, { "offsetInBeginSection": 266, "offsetInEndSection": 431, "text": "We hypothesized that the episomal nature of IDLVs turns them into preferential targets for epigenetic silencing involving chromatin-remodeling histone deacetylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23140481", "endSection": "sections.0" }, { "offsetInBeginSection": 208, "offsetInEndSection": 282, "text": "Silencing involves epigenetic mechanisms, including histone deacetylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104973", "endSection": "sections.0" }, { "offsetInBeginSection": 641, "offsetInEndSection": 811, "text": "Jmjd3 transcription is not induced in Atf4-knock-out cells, but the AAR-dependent activation was rescued by inhibition of histone deacetylation with trichostatin A (TSA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955275", "endSection": "sections.0" }, { "offsetInBeginSection": 1498, "offsetInEndSection": 1717, "text": "We conclude that histone deacetylation is specifically required for the earliest events in appendage regeneration in amphibians, and suggest that this may act as a switch to trigger re-expression of developmental genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22947425", "endSection": "sections.0" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1418, "text": "Inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5aza) and histone deacetylation with Trichostatin A (TSA) resulted in upregulation of EP2 mRNA in all cell lines with varying influences of each epigenetic process observed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22929011", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "During cancer development, tumor suppressor genes were silenced by promoter methylation or histone deacetylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763818", "endSection": "sections.0" }, { "offsetInBeginSection": 114, "offsetInEndSection": 191, "text": "Histone deacetylases (HDACs) are important to maintain histone deacetylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22763818", "endSection": "sections.0" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1354, "text": "Suppression of histone deacetylation and DNA methylation normalized Pomc expression and functional abnormalities.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22622000", "endSection": "sections.0" } ] }, { "body": "Which is the subcellular localization of the protein angiogenin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23843625", "http://www.ncbi.nlm.nih.gov/pubmed/11443914", "http://www.ncbi.nlm.nih.gov/pubmed/7945327", "http://www.ncbi.nlm.nih.gov/pubmed/24603325", "http://www.ncbi.nlm.nih.gov/pubmed/9299500", "http://www.ncbi.nlm.nih.gov/pubmed/22384259", "http://www.ncbi.nlm.nih.gov/pubmed/18246300", "http://www.ncbi.nlm.nih.gov/pubmed/22438557", "http://www.ncbi.nlm.nih.gov/pubmed/21528671" ], "ideal_answer": [ "Under growth conditions, ANG is located in nucleolus where it promotes ribosomal RNA (rRNA) transcription thereby stimulating cell growth. In adverse conditions, ANG is relocated to cytoplasm to promote damage repairs and cell survival." ], "exact_answer": [ "Both nucleolar and cytoplasmic" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051234", "http://www.uniprot.org/uniprot/ANGI_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051641", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051179", "http://www.uniprot.org/uniprot/ANGI_HORSE" ], "type": "factoid", "id": "54d7a1047035c08008000002", "snippets": [ { "offsetInBeginSection": 488, "offsetInEndSection": 725, "text": "Under growth conditions, ANG is located in nucleolus where it promotes ribosomal RNA (rRNA) transcription thereby stimulating cell growth. In adverse conditions, ANG is relocated to cytoplasm to promote damage repairs and cell survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603325", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 184, "text": "Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843625", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 638, "text": "Under growth conditions, ANG is located in the nucleus ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843625", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 957, "text": "Under stress conditions, ANG is localized to the cytoplasm and is concentrated in stress granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843625", "endSection": "abstract" }, { "offsetInBeginSection": 1367, "offsetInEndSection": 1473, "text": "Silencing ANG or inhibiting its nuclear translocation resulted in decreased nuclear LANA-1 and ANG levels,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438557", "endSection": "abstract" }, { "offsetInBeginSection": 1863, "offsetInEndSection": 1928, "text": " results in loss of nuclear translocation activity in ANG mutants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22384259", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 816, "text": "Immunofluorescence staining was applied to investigate co-localization and nuclear translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21528671", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 713, "text": "Recombinant angiogenin was found to mainly concentrate in the pars granulosa of the nucleus, where the protein accumulates to form ribonucleoprotein particles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18246300", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Identification of the nucleolar targeting signal of human angiogenin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7945327", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Angiogenin is endocytosed by subconfluent endothelial cells, translocated to the nucleus and accumulates in the nucleolus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7945327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Nuclear translocation of human angiogenin in cultured human umbilical artery endothelial cells is microtubule and lysosome independent.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9299500", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Exogenous angiogenin undergoes rapid nuclear translocation in cultured human umbilical artery endothelial cells at 37 degrees C but not at 4 degrees ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9299500", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 553, "text": "the nuclear localization of angiogenin in proliferating endothelial cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11443914", "endSection": "abstract" } ] }, { "body": "List FDA approved treatments for androgenetic allopecia", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24170634", "http://www.ncbi.nlm.nih.gov/pubmed/12410672", "http://www.ncbi.nlm.nih.gov/pubmed/20300365", "http://www.ncbi.nlm.nih.gov/pubmed/20426708", "http://www.ncbi.nlm.nih.gov/pubmed/15099321", "http://www.ncbi.nlm.nih.gov/pubmed/21061765", "http://www.ncbi.nlm.nih.gov/pubmed/20689478" ], "ideal_answer": [ "Recently, in addition to the two currently approved U.S. Food and Drug Administration (FDA) medications (minoxidil and finasteride), a novel device was FDA-approved for the treatment of hair loss, the laser hair comb." ], "exact_answer": [ [ "Minoxidil" ], [ "Finasteride" ], [ "Laser hair comb" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000505", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006201", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018859" ], "type": "list", "id": "5324d0169b2d7acc7e000022", "snippets": [ { "offsetInBeginSection": 530, "offsetInEndSection": 774, "text": "Topical minoxidil 2%-5% 1 mL twice daily or finasteride 1 mg daily are recommended as first line treatments, followed by the use of Food and Drug Administration-cleared HairMax LaserComb\u00ae in patients who do not respond to first line modalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170634", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 722, "text": "Recently, in addition to the two currently approved U.S. Food and Drug Administration (FDA) medications (minoxidil and finasteride), a novel device was FDA-approved for the treatment of hair loss, the laser hair comb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21061765", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 489, "text": "In addition, low-level light therapy (LLLT) has recently been approved by the United States Food and Drug Administration (FDA) for the treatment of hair loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20689478", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 681, "text": "Currently there are two U.S. Food and Drug Administration (FDA)-approved agents that promote hair regrowth: over-the-counter topical minoxidil solution for men and women and prescription oral finasteride tablets for men. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12410672", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1043, "text": "Topical monoxidil and oral finasteride are commonly in use and have FDA approval for the treatment of male androgenetic alopecia; dutasteride, a type I and II 5-alpha-reductase inhibitor, is on hold in Phase III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20426708", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 315, "text": "The only FDA-approved dermatological indication of finasteride is androgenetic alopecia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20300365", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 111, "text": "Finasteride (Propecia) was approved by the FDA in 1998 for treating men with androgenetic alopecia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15099321", "endSection": "abstract" } ] }, { "body": "Which bone protein is used in archaelogy for dating and species identification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22956324", "http://www.ncbi.nlm.nih.gov/pubmed/21800128", "http://www.ncbi.nlm.nih.gov/pubmed/20131322", "http://www.ncbi.nlm.nih.gov/pubmed/18174420", "http://www.ncbi.nlm.nih.gov/pubmed/22517758", "http://www.ncbi.nlm.nih.gov/pubmed/16323185", "http://www.ncbi.nlm.nih.gov/pubmed/21959970", "http://www.ncbi.nlm.nih.gov/pubmed/1910520", "http://www.ncbi.nlm.nih.gov/pubmed/21606484", "http://www.ncbi.nlm.nih.gov/pubmed/16921562", "http://www.ncbi.nlm.nih.gov/pubmed/24327307", "http://www.ncbi.nlm.nih.gov/pubmed/24019191", "http://www.ncbi.nlm.nih.gov/pubmed/22125157", "http://www.ncbi.nlm.nih.gov/pubmed/19899187", "http://www.ncbi.nlm.nih.gov/pubmed/21953954", "http://www.ncbi.nlm.nih.gov/pubmed/21953952" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0026102", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0003733", "o": "http://linkedlifedata.com/resource/umls/label/A0026106" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0003733", "o": "http://linkedlifedata.com/resource/umls/label/A0026102" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0026106", "o": "Archeology" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0003733", "o": "http://linkedlifedata.com/resource/umls/label/A1387406" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0003733", "o": "http://linkedlifedata.com/resource/umls/label/A0026101" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0026102", "o": "Archaeology" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1387406", "o": "archaeology" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0003733", "o": "http://linkedlifedata.com/resource/umls/label/A0026101" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0026106", "o": "MeSH" } ], "ideal_answer": [ "Collagen is the main protein extracted from bones and analyzed by mass spectrometry. It is traditionally used for radiocarbon dating but sophisticated new technologies are using collagen for species identification as well." ], "exact_answer": [ "Collagen" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021241", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018629", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060348", "http://www.disease-ontology.org/api/metadata/DOID:0080001", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053719", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0038055", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001503", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013057", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001842", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001106" ], "type": "factoid", "id": "55054f8af73303d458000002", "snippets": [ { "offsetInBeginSection": 322, "offsetInEndSection": 503, "text": "Collagen was extracted from modern and archaeological cod bones using a weak HCl solution and analysed for its sulphur isotopic composition by isotope ratio mass spectrometry (IRMS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24019191", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 514, "text": "With the high sensitivity of current generation mass spectrometers, ZooMS provides a non-destructive and highly cost-effective method to characterise collagen peptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Archaeological bones are usually dated by radiocarbon measurement of extracted collagen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22517758", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 451, "text": "we describe three complementary preparative HPLC procedures suitable for separating and isolating single amino acids from bone collagen or hair keratin with minimal isotopic contamination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22125157", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 508, "text": "Bulk bone collagen isotopic analysis of 11 skeletons of Iron Age and Roman date gave a typical C(3) terrestrial signal (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21959970", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Comparison of liquid chromatography-isotope ratio mass spectrometry (LC/IRMS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) for the determination of collagen amino acid \u03b413C values for palaeodietary and palaeoecological reconstruction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953954", "endSection": "title" }, { "offsetInBeginSection": 230, "offsetInEndSection": 501, "text": "Although the primary focus was the compound-specific stable carbon isotope analysis of bone collagen AAs, because of its growing application for palaeodietary and palaeoecological reconstruction, the results are relevant to any field where AA \u03b4(13)C values are required. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "In archaeological studies, the isotopic enrichment values of carbon and nitrogen in bone collagen give a degree of information on dietary composition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Liquid chromatography/isotope ratio mass spectrometry measurement of \u03b413C of amino acids in plant proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953952", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A new procedure for extraction of collagen from modern and archaeological bones for 14C dating.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21800128", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Bones are potentially the best age indicators in a stratigraphic study, because they are closely related to the layer in which they are found. Collagen is the most suitable fraction and is the material normally used in radiocarbon dating.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21800128", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 932, "text": "The developed strategy permitted unprecedented biochemical analyses of bone-matrix proteins, including collagen modifications, using nearly nanoscale amounts of exceptionally homogenous bone tissue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Amino acid delta13C analysis of hair proteins and bone collagen using liquid chromatography/isotope ratio mass spectrometry: paleodietary implications from intra-individual comparisons.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20131322", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "We report a novel method for the chromatographic separation and measurement of stable carbon isotope ratios (delta(13)C) of individual amino acids in hair proteins and bone collagen using the LC-IsoLink system, which interfaces liquid chromatography (LC) with isotope ratio mass spectrometry (IRMS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20131322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Species identification by analysis of bone collagen using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19899187", "endSection": "title" }, { "offsetInBeginSection": 419, "offsetInEndSection": 612, "text": "Analysis of the collagen from 32 different mammal species identified a total of 92 peptide markers that could be used for species identification, for example, in processed food and animal feed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19899187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "We used authentication tests developed for ancient DNA to evaluate claims by Asara et al. (Reports, 13 April 2007, p. 280) of collagen peptide sequences recovered from mastodon and Tyrannosaurus rex fossils", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Analysis of amino acid 13C abundance from human and faunal bone collagen using liquid chromatography/isotope ratio mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16921562", "endSection": "title" }, { "offsetInBeginSection": 89, "offsetInEndSection": 317, "text": "Stable nitrogen (delta(15)N) and carbon (delta(13)C) isotope ratios were measured in bone collagen and dentine from human skeletons excavated from this site in order to establish a weaning curve in mid-Holocene hunter-gatherers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16323185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Mass spectrometric analysis of the stable carbon isotope composition (13C/12C or delta 13C) of bone collagen from human remains recovered at archaeological sites provides a direct chemical method for investigating dietary patterns of prehistoric human populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1910520", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1541, "text": "Coupled with more traditional archaeological methods, stable carbon isotope analysis of bone collagen can significantly enhance reconstruction of dietary patterns of prehistoric humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1910520", "endSection": "abstract" } ] }, { "body": "Does thyroid hormone affect cardiac remodeling ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24195179", "http://www.ncbi.nlm.nih.gov/pubmed/23532677", "http://www.ncbi.nlm.nih.gov/pubmed/23409791", "http://www.ncbi.nlm.nih.gov/pubmed/17315395", "http://www.ncbi.nlm.nih.gov/pubmed/24152286", "http://www.ncbi.nlm.nih.gov/pubmed/24014964", "http://www.ncbi.nlm.nih.gov/pubmed/19096930", "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "http://www.ncbi.nlm.nih.gov/pubmed/23990180", "http://www.ncbi.nlm.nih.gov/pubmed/24159562", "http://www.ncbi.nlm.nih.gov/pubmed/23958074", "http://www.ncbi.nlm.nih.gov/pubmed/21568669", "http://www.ncbi.nlm.nih.gov/pubmed/24157158", "http://www.ncbi.nlm.nih.gov/pubmed/24315768", "http://www.ncbi.nlm.nih.gov/pubmed/24114432", "http://www.ncbi.nlm.nih.gov/pubmed/23554452", "http://www.ncbi.nlm.nih.gov/pubmed/24187401", "http://www.ncbi.nlm.nih.gov/pubmed/24322910", "http://www.ncbi.nlm.nih.gov/pubmed/24217559", "http://www.ncbi.nlm.nih.gov/pubmed/19107595", "http://www.ncbi.nlm.nih.gov/pubmed/22649319", "http://www.ncbi.nlm.nih.gov/pubmed/23555069", "http://www.ncbi.nlm.nih.gov/pubmed/23762386", "http://www.ncbi.nlm.nih.gov/pubmed/24246300", "http://www.ncbi.nlm.nih.gov/pubmed/9489964", "http://www.ncbi.nlm.nih.gov/pubmed/19125327", "http://www.ncbi.nlm.nih.gov/pubmed/16719939" ], "ideal_answer": [ "Cardiac function and mechanics are significantly affected by low thyroid function. l-T4 therapy improves but does not completely recover cardiac function in patients with mild hypothyroidism.\nLong-term T4 treatment after myocardial infarction has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011989", "http://www.biosemantics.org/jochem#4250045", "http://www.uniprot.org/uniprot/TSHR_MOUSE", "http://www.biosemantics.org/jochem#4275389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ], "type": "yesno", "id": "52e7b4a198d023950500001b", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 88, "text": "Thyroid hormones exert important effects on heart remodeling through mir-208.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246300", "endSection": "abstract" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1750, "text": "RV and RA function and mechanics are significantly affected by SHT. l-T4 therapy and 1-year maintenance of euthyroid status improved but did not completely recover RV and RA function and deformation in the SHT patients, which implies that right heart remodeling caused by SHT is not reversible in a 1-year period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114432", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1998, "text": "These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23409791", "endSection": "abstract" } ] }, { "body": "What is the effect of SAHA treatment in Huntington's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21726209", "http://www.ncbi.nlm.nih.gov/pubmed/22140466", "http://www.ncbi.nlm.nih.gov/pubmed/19484127", "http://www.ncbi.nlm.nih.gov/pubmed/12576549" ], "ideal_answer": [ "Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, protects dopaminergic neurons from neurotoxin-induced damage. SAHA is predominantly an inhibitor of class I HDACs. However, it can also bind to class IIa HDACs and has been shown to degrade class IIa HDACs at the protein level in vitro. The neuroprotective effects of SAHA were mediated in part by promoting release of neurotrophic factors from astroglia through inhibition of histone deacetylation. SAHA can lead to the degradation of class IIa HDACs 4 and 5 via RANBP2 mediated proteasome degradation in vitro." ], "concepts": [ "http://www.biosemantics.org/jochem#4267272", "http://www.disease-ontology.org/api/metadata/DOID:12858" ], "type": "summary", "id": "516e5f4e298dcd4e51000080", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12576549", "endSection": "title" }, { "offsetInBeginSection": 497, "offsetInEndSection": 793, "text": "To further explore the therapeutic potential of HDAC inhibitors, we have conducted preclinical trials with suberoylanilide hydroxamic acid (SAHA), a potent HDAC inhibitor, in the R6/2 HD mouse model. We show that SAHA crosses the blood-brain barrier and increases histone acetylation in the brain", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12576549", "endSection": "sections.0" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1035, "text": "SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12576549", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, protects dopaminergic neurons from neurotoxin-induced damage", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21726209", "endSection": "title" }, { "offsetInBeginSection": 428, "offsetInEndSection": 736, "text": "Suberoylanilide hydroxamic acid (SAHA) was the first HDAC inhibitor approved by the Food and Drug Administration for the sole use of cancer therapy. The purpose of this study was to explore the potential new indications of SAHA for therapy of neurodegenerative diseases in in vitro Parkinson's disease models", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21726209", "endSection": "sections.0" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1718, "text": "The novel neurotrophic and neuroprotective effects of SAHA demonstrated in this study suggest that further study of this HDAC inhibitor could provide a new therapeutic approach to the treatment of neurodegenerative diseases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21726209", "endSection": "sections.0" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1283, "text": "SAHA displayed dose- and time-dependent prolongation of the survival and protection against neurotoxin-induced neuronal death of dopaminergic neurons", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21726209", "endSection": "sections.0" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1480, "text": "neuroprotective effects of SAHA were mediated in part by promoting release of neurotrophic factors from astroglia through inhibition of histone deacetylation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21726209", "endSection": "sections.0" } ] }, { "body": "What is known about the role of mHealth in the prevention of disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24133558", "http://www.ncbi.nlm.nih.gov/pubmed/22548595", "http://www.ncbi.nlm.nih.gov/pubmed/23330022", "http://www.ncbi.nlm.nih.gov/pubmed/23549699", "http://www.ncbi.nlm.nih.gov/pubmed/23624056", "http://www.ncbi.nlm.nih.gov/pubmed/24246427", "http://www.ncbi.nlm.nih.gov/pubmed/22920991", "http://www.ncbi.nlm.nih.gov/pubmed/22548607", "http://www.ncbi.nlm.nih.gov/pubmed/24050486", "http://www.ncbi.nlm.nih.gov/pubmed/23992038", "http://www.ncbi.nlm.nih.gov/pubmed/24294329" ], "ideal_answer": [ "Most reported uses of mHealth are for treatment, we identified report on approaches to child obesity prevention." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055502", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011322" ], "type": "summary", "id": "535d7c247d100faa09000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "mHealth approaches to child obesity prevention", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24294329", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Daily text messaging for weight control among racial and ethnic minority women", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246427", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 378, "text": "text messaging intervention for weight loss among predominantly black women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246427", "endSection": "abstract" }, { "offsetInBeginSection": 1660, "offsetInEndSection": 1843, "text": "Given the increasing penetration of mobile devices, text messaging may be a useful self-monitoring tool for weight control, particularly among populations most in need of intervention", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246427", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1151, "text": "The review revealed evidence that mHealth tools support HIV programmatic priorities, including: linkage to care, retention in care, and adherence to antiretroviral treatment. In terms of technical features, mHealth tools facilitate alerts and reminders, data collection, direct voice communication, educational messaging, information on demand, and more", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24133558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Mobile health messages help sustain recent weight loss.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24050486", "endSection": "title" }, { "offsetInBeginSection": 1076, "offsetInEndSection": 1272, "text": " A clinically significant decrease in mean weight, higher rate of sustained weight loss, and medium-to-large effects on sustained weight loss occurred in the promotion and prevention interventions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24050486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "A mobile health intervention for weight management among young adults:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23992038", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "HIV prevalence in Uganda has leveled off, however trends indicate that incidence is on the rise and disproportionately affects certain vulnerable groups, such as women. There is growing support for using mobile health (mHealth) programs to reach vulnerable populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23549699", "endSection": "abstract" }, { "offsetInBeginSection": 1763, "offsetInEndSection": 1915, "text": "We successully designed and implemented a mobile phone SMS-based system to track pregnancy and maternal and child outcomes in limited resources setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23330022", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 841, "text": "The purpose of the study, Project ACTION (Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods), is to utilize a mobile clinic model, a network of community sites (i.e., community centers and churches) and an interactive mobile messaging system to reach and deliver smoking cessation treatment to underserved, low-income communities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22920991", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1749, "text": "Participants were randomized to usual prenatal care plus text messaging or usual care alone. The evaluation has a theoretical model of behavior change and measures mediators as well as behavioral outcomes. Results will inform how behavioral theory works within mobile health programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22548595", "endSection": "abstract" } ] }, { "body": "Which receptors are targeted by suvorexant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24215799", "http://www.ncbi.nlm.nih.gov/pubmed/21473737", "http://www.ncbi.nlm.nih.gov/pubmed/24488306", "http://www.ncbi.nlm.nih.gov/pubmed/24680372", "http://www.ncbi.nlm.nih.gov/pubmed/23024835", "http://www.ncbi.nlm.nih.gov/pubmed/23964859", "http://www.ncbi.nlm.nih.gov/pubmed/22920041", "http://www.ncbi.nlm.nih.gov/pubmed/25489915", "http://www.ncbi.nlm.nih.gov/pubmed/25147058", "http://www.ncbi.nlm.nih.gov/pubmed/22725839", "http://www.ncbi.nlm.nih.gov/pubmed/23197752", "http://www.ncbi.nlm.nih.gov/pubmed/23692283", "http://www.ncbi.nlm.nih.gov/pubmed/25407283", "http://www.ncbi.nlm.nih.gov/pubmed/25197807", "http://www.ncbi.nlm.nih.gov/pubmed/25533960", "http://www.ncbi.nlm.nih.gov/pubmed/24757363", "http://www.ncbi.nlm.nih.gov/pubmed/25397996", "http://www.ncbi.nlm.nih.gov/pubmed/24942635", "http://www.ncbi.nlm.nih.gov/pubmed/21528938", "http://www.ncbi.nlm.nih.gov/pubmed/25227290", "http://www.ncbi.nlm.nih.gov/pubmed/23282091", "http://www.ncbi.nlm.nih.gov/pubmed/25291725", "http://www.ncbi.nlm.nih.gov/pubmed/23359095", "http://www.ncbi.nlm.nih.gov/pubmed/23731216", "http://www.ncbi.nlm.nih.gov/pubmed/23372274", "http://www.ncbi.nlm.nih.gov/pubmed/24550770" ], "ideal_answer": [ "Suvorexant is a potent, selective, and orally bioavailable antagonist of orexin 1 receptor and orexin 2 receptor currently under clinical investigation as a novel therapy for insomnia." ], "exact_answer": [ [ "orexin 1" ], [ "orexin 2" ] ], "type": "list", "id": "54fc9ca16ad7dcbc12000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Dual orexin receptor (OXR) antagonists (DORAs) such as almorexant, 1 (SB-649868), or suvorexant have shown promise for the treatment of insomnias and sleep disorders in several recent clinical trials in volunteers and primary insomnia patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964859", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 267, "text": "Several such compounds have entered into clinical development, including the dual orexin receptor antagonists, suvorexant and almorexant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692283", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 119, "text": " Suvorexant (MK-4305) is an orexin receptor antagonist being developed for the treatment of insomnia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23372274", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 944, "text": "Indeed, phase III clinical trials were completed last year of suvorexant, a non-selective (dual) antagonist for orexin receptors, for the treatment of primary insomnia, and demonstrate promising results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359095", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 327, "text": "METHODS: We evaluated suvorexant, an orexin receptor antagonist, for treating patients with primary insomnia in a randomized, double-blind, placebo-controlled, 2-period (4 weeks per period) crossover polysomnography study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23197752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Suvorexant is a dual orexin antagonist currently in Phase III clinical trials for the modulation of sleep and is being developed by Merck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024835", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 755, "text": "Merck's suvorexant (MK-4305) is the first compound of the so-called dual orexin receptor antagonist (DORA) class expected to be submitted for FDA approval, with a new drug application anticipated in 2012. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22920041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A concise, enantioselective synthesis of the potent dual orexin inhibitor suvorexant (1) is reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22725839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Reaction development and mechanistic study of a ruthenium catalyzed intramolecular asymmetric reductive amination en route to the dual Orexin inhibitor Suvorexant (MK-4305).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21528938", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The first example of an intramolecular asymmetric reductive amination of a dialkyl ketone with an aliphatic amine has been developed for the synthesis of Suvorexant (MK-4305), a potent dual Orexin antagonist under development for the treatment of sleep disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21528938", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 578, "text": "Suvorexant (MK-4305) is a potent, selective, and orally bioavailable antagonist of OX(1)R and OX(2)R currently under clinical investigation as a novel therapy for insomnia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21473737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Suvorexant is a pharmacologically novel dual antagonist of orexin receptors OX1R and OX2R, which has an effect that promotes sleep by reducing arousal and wakefulness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25291725", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 940, "text": " Indeed, phase III clinical trials were completed last year of suvorexant, a non-selective (dual) antagonist for orexin receptors, for the treatment of primary insomnia, and demonstrate promising results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359095", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 506, "text": " In order to understand the differential contribution of both receptors in regulating sleep/wakefulness states we compared the pharmacological effects of a newly developed OX2R antagonist (2-SORA), Compound 1 m (C1 m), with those of a dual orexin receptor antagonist (DORA), suvorexant, in C57BL/6J mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24550770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21473737", "endSection": "title" } ] }, { "body": "Is armodafinil used for treatment of insomnia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20051221", "http://www.ncbi.nlm.nih.gov/pubmed/21275439", "http://www.ncbi.nlm.nih.gov/pubmed/19880686", "http://www.ncbi.nlm.nih.gov/pubmed/21904092", "http://www.ncbi.nlm.nih.gov/pubmed/20957846", "http://www.ncbi.nlm.nih.gov/pubmed/16861091", "http://www.ncbi.nlm.nih.gov/pubmed/16908126", "http://www.ncbi.nlm.nih.gov/pubmed/16684437", "http://www.ncbi.nlm.nih.gov/pubmed/17181377", "http://www.ncbi.nlm.nih.gov/pubmed/18596995", "http://www.ncbi.nlm.nih.gov/pubmed/22353444", "http://www.ncbi.nlm.nih.gov/pubmed/17874255", "http://www.ncbi.nlm.nih.gov/pubmed/20074507" ], "ideal_answer": [ "No, armodafinil is not used for treatment of insomnia. Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD." ], "exact_answer": "no", "concepts": [ "http://www.biosemantics.org/jochem#4216693" ], "type": "yesno", "id": "54f1e781c409818c32000003", "snippets": [ { "offsetInBeginSection": 1036, "offsetInEndSection": 1256, "text": " Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444", "endSection": "abstract" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1158, "text": "Other treatment options may include pharmacologic interventions such as modafinil and armodafinil, which have shown efficacy in this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21904092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 522, "text": "BACKGROUND: Armodafinil (Nuvigil(\u00ae), Cephalon, Inc., Frazer, PA, USA), the longer-lasting isomer of racemic modafinil, is a nonamphetamine, wakefulness-promoting medication. In patients with excessive sleepiness associated with shift work disorder, treated obstructive sleep apnoea, or narcolepsy, armodafinil has been found to improve wakefulness throughout the shift or day. In addition, while not approved for this indication, armodafinil has been found to improve excessive sleepiness associated with jet-lag disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21275439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "STUDY OBJECTIVES: Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20957846", "endSection": "abstract" }, { "offsetInBeginSection": 1820, "offsetInEndSection": 1945, "text": "Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20957846", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 624, "text": "The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074507", "endSection": "abstract" }, { "offsetInBeginSection": 2327, "offsetInEndSection": 2532, "text": "CONCLUSIONS: Armodafinil significantly improved overall clinical condition related to excessive sleepiness as rated by the CGI-C and was well tolerated in patients with treated OSA and comorbid depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20051221", "endSection": "abstract" }, { "offsetInBeginSection": 1910, "offsetInEndSection": 2324, "text": "CONCLUSION: In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19880686", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1490, "text": "Adjunct treatment with armodafinil significantly improved wakefulness, long-term memory, and patients' ability to engage in activities of daily living in nCPAP-adherent individuals with ES associated with OSA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17874255", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 1004, "text": "A number of studies have evaluated countermeasures or interventions in shift workers; proposed treatments include chronobiotic interventions, such as light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants (amphetamine), and the wake-promoting agents modafinil and armodafinil. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17181377", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1788, "text": "These studies showed that modafinil and armodafinil significantly improve the ability to sustain wakefulness during waking activities (e.g. working, driving), overall clinical condition, and sustained attention or memory in patients with SWSD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17181377", "endSection": "abstract" }, { "offsetInBeginSection": 3148, "offsetInEndSection": 3395, "text": "CONCLUSIONS: In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16861091", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1218, "text": " Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 276, "text": "Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20957846", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1228, "text": "Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22353444", "endSection": "abstract" }, { "offsetInBeginSection": 3111, "offsetInEndSection": 3343, "text": "In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16861091", "endSection": "abstract" } ] }, { "body": "A common problem in proteomics is the contamination of samples with exogenous proteins (often from other species). These proteins can be found in specific databases. List some contaminants.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12422360", "http://www.ncbi.nlm.nih.gov/pubmed/22954629", "http://www.ncbi.nlm.nih.gov/pubmed/12915006", "http://www.ncbi.nlm.nih.gov/pubmed/12872232", "http://www.ncbi.nlm.nih.gov/pubmed/20641139" ], "ideal_answer": [ "Some common contaminants in proteomics are proteases (used for the digestion of the proteins), keratins (usually from the skin), proteins originated from the serum of the culture media and antibodies if used in the experiment." ], "exact_answer": [ [ "Proteases" ], [ "Keratins" ], [ "Bovine serum proteins" ], [ "Antibodies" ] ], "type": "list", "id": "515d7693298dcd4e5100000c", "snippets": [ { "offsetInBeginSection": 312, "offsetInEndSection": 355, "text": "protease autolysis or keratin contaminants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12422360", "endSection": "sections.0" }, { "offsetInBeginSection": 515, "offsetInEndSection": 598, "text": "Most of the interfering masses originate from trypsin autolysis and human keratins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12872232", "endSection": "sections.0" }, { "offsetInBeginSection": 139, "offsetInEndSection": 271, "text": "5-15% FBS. Contamination by bovine proteins is difficult to avoid because of adherence to the plastic vessel and the cultured cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20641139", "endSection": "sections.0" }, { "offsetInBeginSection": 221, "offsetInEndSection": 389, "text": "The main disadvantage of traditional IP and co-IP is that the conditions used to elute the precipitated antigen also release the antibody thus contaminating the antigen", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12915006", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "MaConDa: a publicly accessible mass spectrometry contaminants database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22954629", "endSection": "title" } ] }, { "body": "Which gene has been implicated in Majeed Syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19369868", "http://www.ncbi.nlm.nih.gov/pubmed/15994876", "http://www.ncbi.nlm.nih.gov/pubmed/19717560", "http://www.ncbi.nlm.nih.gov/pubmed/22127713", "http://www.ncbi.nlm.nih.gov/pubmed/24811178", "http://www.ncbi.nlm.nih.gov/pubmed/22908270", "http://www.ncbi.nlm.nih.gov/pubmed/25300978", "http://www.ncbi.nlm.nih.gov/pubmed/17330256", "http://www.ncbi.nlm.nih.gov/pubmed/20032092", "http://www.ncbi.nlm.nih.gov/pubmed/23087183", "http://www.ncbi.nlm.nih.gov/pubmed/16122996" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0062665", "o": "D005796" } ], "ideal_answer": [ "Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome).", "Genetic alteration of LPIN2 in humans is known to cause Majeed syndrome." ], "exact_answer": [ "LPIN2" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "factoid", "id": "56f7c15a09dd18d46b000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15994876", "endSection": "title" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1250, "text": "The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15994876", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1459, "text": "We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15994876", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 401, "text": " genetic alteration of LPIN2 in humans is known to cause Majeed syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24811178", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 254, "text": "Majeed syndrome is an autosomal recessive disorder characterised by the triad of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anaemia and a neutrophilic dermatosis that is caused by mutations in LPIN2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23087183", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 438, "text": "ittle is known about the physiological role of lipin-2, the predominant lipin protein present in liver and the deficient gene product in the rare disorder Majeed syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908270", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 807, "text": "Recent studies have identified mutations that cause lipin-1 or lipin-2 deficiency in humans, leading to acute myoglobinuria in childhood or the inflammatory disorder Majeed syndrome, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369868", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 360, "text": "An S734L mutation in LPIN2 causes Majeed syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19717560", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 608, "text": "Little is known about the physiological role of lipin-2, the predominant lipin protein present in liver and the deficient gene product in the rare disorder Majeed syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "A splice site mutation confirms the role of LPIN2 in Majeed syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17330256", "endSection": "title" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1071, "text": "These data confirm the role of LPIN2 mutations in the etiology of Majeed syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17330256", "endSection": "abstract" } ] }, { "body": "What is Trypan blue used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24160177", "http://www.ncbi.nlm.nih.gov/pubmed/24289578", "http://www.ncbi.nlm.nih.gov/pubmed/24212220", "http://www.ncbi.nlm.nih.gov/pubmed/24123008", "http://www.ncbi.nlm.nih.gov/pubmed/24139500", "http://www.ncbi.nlm.nih.gov/pubmed/24228750", "http://www.ncbi.nlm.nih.gov/pubmed/24238300", "http://www.ncbi.nlm.nih.gov/pubmed/24190701", "http://www.ncbi.nlm.nih.gov/pubmed/24231574", "http://www.ncbi.nlm.nih.gov/pubmed/24127887", "http://www.ncbi.nlm.nih.gov/pubmed/24279639", "http://www.ncbi.nlm.nih.gov/pubmed/24296136", "http://www.ncbi.nlm.nih.gov/pubmed/24320727", "http://www.ncbi.nlm.nih.gov/pubmed/24236478", "http://www.ncbi.nlm.nih.gov/pubmed/24129092", "http://www.ncbi.nlm.nih.gov/pubmed/24228508", "http://www.ncbi.nlm.nih.gov/pubmed/24316855", "http://www.ncbi.nlm.nih.gov/pubmed/23354080", "http://www.ncbi.nlm.nih.gov/pubmed/24300339", "http://www.ncbi.nlm.nih.gov/pubmed/24256980", "http://www.ncbi.nlm.nih.gov/pubmed/24304568", "http://www.ncbi.nlm.nih.gov/pubmed/24312318", "http://www.ncbi.nlm.nih.gov/pubmed/24195509", "http://www.ncbi.nlm.nih.gov/pubmed/24140394", "http://www.ncbi.nlm.nih.gov/pubmed/24244400" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A9452169", "o": "d05534" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A9452169", "o": "trypan blue ophthalmic" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1655623", "o": "http://linkedlifedata.com/resource/umls/label/A9452169" }, { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Trypan+Blue", "o": "72-57-1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Trypan+Blue", "o": "Trypan Blue" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8424406", "o": "C003915" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1565627", "o": "http://linkedlifedata.com/resource/umls/label/A8424406" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8424406", "o": "Trypan" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1565627", "o": "http://linkedlifedata.com/resource/umls/label/A8424406" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3907535", "o": "Metathesaurus Names" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1318869", "o": "http://linkedlifedata.com/resource/umls/label/A3907535" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3907535", "o": "Trypan blue stain method" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1318869", "o": "http://linkedlifedata.com/resource/umls/label/A3907535" } ], "ideal_answer": [ "Trypan blue is used in the \"trypan blue exclusion assay\" for assessing cell viability/cell death." ], "exact_answer": [ "cell viability - cell death assessment" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014343", "http://www.biosemantics.org/jochem#4250111", "http://www.biosemantics.org/jochem#4251229" ], "type": "factoid", "id": "5523e7837b523f2123000006", "snippets": [ { "offsetInBeginSection": 300, "offsetInEndSection": 342, "text": " cell death by trypan blue exclusion assay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354080", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1277, "text": "Examination of cell viability in UCP2-transfected cells with Trypan Blue and Annexin-V staining revealed that UCP2 transfection led to significantly increased cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320727", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 495, "text": "assessed for their viability by vital staining (Trypan blue)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24316855", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 961, "text": "the trypan blue exclusion test of cell viability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24312318", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 543, "text": " Cell viability was determined by MTT, neutral red uptake and trypan blue exclusion assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304568", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 637, "text": "Cytotoxicity, apoptosis, and necrosis were investigated by trypan blue exclusion, MTT assay, and annexin V/propidium iodide assay, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24300339", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 586, "text": "Cytotoxicity was measured using the Trypan Blue Dye Exclusion assay and genotoxicity using the Comet Assay (alkaline single-cell electrophoresis)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24296136", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 555, "text": "Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289578", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 502, "text": "cell viability was measured using an MTT assay and the trypan blue exclusion method, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24279639", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 775, "text": "Cell viability and apoptosis assay using MTT analysis and trypan blue staining,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256980", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1055, "text": "cell death was assayed by trypan blue exclusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24244400", "endSection": "abstract" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1307, "text": "cell viability (Trypan Blue)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24238300", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 869, "text": "cell viability using both Trypan Blue dye exclusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24238300", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 482, "text": " cell-viability analysis with trypan blue ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24236478", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 911, "text": " Specimens were examined for keratinocyte survival at 7, 14, 21, 28, and 35 days using the trypan blue assay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231574", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 653, "text": "For cytotoxicity testing, relative growth activity, trypan blue exclusion, (3)H-thymidine incorporation and cytokinesis-block proliferation index were assessed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24228750", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1046, "text": "trypan blue was used to detect cell viability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24228508", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 415, "text": "Cell viability was measured by a trypan blue dye exclusion test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212220", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 675, "text": " Cell viability was determined using the trypan blue exclusion assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24195509", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 459, "text": "Cell death was analyzed by MTT viability assay and trypan blue staining.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24190701", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 711, "text": " cell viability was determined by trypan blue exclusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24160177", "endSection": "abstract" }, { "offsetInBeginSection": 1665, "offsetInEndSection": 1705, "text": " the cell viability (trypan blue method)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140394", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 328, "text": "trypan blue staining to test the viability of cancer cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24139500", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 749, "text": " Cell viability and survival were assessed using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and trypan blue exclusion assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129092", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 412, "text": " Viability and proliferation of immobilized DPSCs were determined by trypan blue and MTT assay, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24127887", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 476, "text": " Cell proliferation and viability were assessed using trypan blue and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24123008", "endSection": "abstract" } ] }, { "body": "Selexipag is used for which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "http://www.ncbi.nlm.nih.gov/pubmed/22362844", "http://www.ncbi.nlm.nih.gov/pubmed/26152132", "http://www.ncbi.nlm.nih.gov/pubmed/22918043", "http://www.ncbi.nlm.nih.gov/pubmed/25277144" ], "ideal_answer": [ "Selexipag is a novel, oral, selective prostacyclin (PGI2) receptor agonist in clinical development for the treatment of pulmonary arterial hypertension." ], "exact_answer": [ "pulmonary arterial hypertension" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812" ], "type": "factoid", "id": "56c1f045ef6e394741000058", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "OBJECTIVE: Selexipag is a novel, oral, selective prostacyclin (PGI2) receptor agonist in clinical development for the treatment of pulmonary arterial hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Selexipag for the treatment of pulmonary arterial hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "title" }, { "offsetInBeginSection": 107, "offsetInEndSection": 253, "text": "This review was based on a PubMed search and focuses on the potential role of selexipag in the treatment of pulmonary arterial hypertension (PAH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1030, "text": "Selexipag showed effects on pharmacodynamic end points obtained with right heart catheterization in a Phase II trial in patients with PAH, and is being evaluated in the ongoing Phase III trial (GRIPHON trial, Clinicaltrials.gov NCT01106014).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1314, "text": "Pending the GRIPHON trial results, selexipag could provide a convenient first-line prostacyclin treatment option for patients with PAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "OBJECTIVE: The objective of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of selexipag, an orally available selective prostacyclin receptor agonist, in development for pulmonary arterial hypertension in healthy subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25277144", "endSection": "abstract" }, { "offsetInBeginSection": 2013, "offsetInEndSection": 2284, "text": "These data demonstrate that the relaxant efficacy of the selective IP receptor agonist selexipag and its metabolite ACT-333679 is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence of mediators of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918043", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1414, "text": "Our results encourage the further investigation of selexipag for the treatment of PAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362844", "endSection": "title" }, { "offsetInBeginSection": 1762, "offsetInEndSection": 2032, "text": "These data demonstrate that the relaxant efficacy of the selective IP receptor agonist selexipag and its metabolite ACT-333679 is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence of mediators of disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "OBJECTIVE: Selexipag is a novel, oral, selective prostacyclin (PGI2) receptor agonist in clinical development for the treatment of pulmonary arterial hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152132", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 239, "text": "This review was based on a PubMed search and focuses on the potential role of selexipag in the treatment of pulmonary arterial hypertension (PAH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 1002, "text": "Selexipag showed effects on pharmacodynamic end points obtained with right heart catheterization in a Phase II trial in patients with PAH, and is being evaluated in the ongoing Phase III trial (GRIPHON trial, Clinicaltrials.gov NCT01106014).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1271, "text": "Pending the GRIPHON trial results, selexipag could provide a convenient first-line prostacyclin treatment option for patients with PAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "abstract" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1274, "text": " The signal of a beneficial effect of selexipag on disease progression may become more robust for long term under prolonged exposure. Pending the GRIPHON trial results, selexipag could provide a convenient first-line prostacyclin treatment option for patients with PAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "abstract" }, { "offsetInBeginSection": 1753, "offsetInEndSection": 2024, "text": "These data demonstrate that the relaxant efficacy of the selective IP receptor agonist selexipag and its metabolite ACT-333679 is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence of mediators of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Selexipag for the treatment of pulmonary arterial hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392948", "endSection": "title" } ] }, { "body": "How does ranolazine affect kinase signaling activation in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23271797", "http://www.ncbi.nlm.nih.gov/pubmed/21677263" ], "ideal_answer": [ "Ranolazine inhibits Ca(2+)/calmodulin kinase II (CaMKII) activity" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008349", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020930", "http://www.biosemantics.org/jochem#4202863", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048670", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042656", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004709", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000185", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048730", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048848", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048728", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048490", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0033161", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043549" ], "type": "summary", "id": "517138b68ed59a060a000002", "snippets": [ { "offsetInBeginSection": 1029, "offsetInEndSection": 1383, "text": "support of this view, CaMKII activity was also increased in hearts of transgenic mice overexpressing a gain-of-function Na(v)1.5 mutant (N(1325)S). The effects of both ATX-II and the N(1325)S mutation were reversed by either I(NaL) inhibition (with ranolazine or tetrodotoxin) or CaMKII inhibition (with KN93 or autocamtide 2-related inhibitory peptide).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21677263", "endSection": "sections.0" }, { "offsetInBeginSection": 820, "offsetInEndSection": 1463, "text": "Such changes were related to enhanced Ca(2+)/calmodulin kinase II (CaMKII) activity and increased phosphorylation of its targets. Ranolazine at therapeutic concentrations partially reversed the HCM-related cellular abnormalities via I(NaL) inhibition, with negligible effects in controls. By shortening the action potential duration in HCM cardiomyocytes, ranolazine reduced the occurrence of early and delayed afterdepolarizations. Finally, as a result of the faster kinetics of Ca(2+)(i) transients and the lower diastolic Ca(2+)(i), ranolazine accelerated the contraction-relaxation cycle of HCM trabeculae, ameliorating diastolic function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23271797", "endSection": "sections.0" } ] }, { "body": "List features of the DEND syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "http://www.ncbi.nlm.nih.gov/pubmed/20368737", "http://www.ncbi.nlm.nih.gov/pubmed/16123337", "http://www.ncbi.nlm.nih.gov/pubmed/19169493", "http://www.ncbi.nlm.nih.gov/pubmed/22326206", "http://www.ncbi.nlm.nih.gov/pubmed/16609879", "http://www.ncbi.nlm.nih.gov/pubmed/23783767", "http://www.ncbi.nlm.nih.gov/pubmed/16670688", "http://www.ncbi.nlm.nih.gov/pubmed/16019717", "http://www.ncbi.nlm.nih.gov/pubmed/23462667", "http://www.ncbi.nlm.nih.gov/pubmed/22768671", "http://www.ncbi.nlm.nih.gov/pubmed/17652641", "http://www.ncbi.nlm.nih.gov/pubmed/22145471", "http://www.ncbi.nlm.nih.gov/pubmed/22694282", "http://www.ncbi.nlm.nih.gov/pubmed/24150202", "http://www.ncbi.nlm.nih.gov/pubmed/19686306" ], "ideal_answer": [ "Clinical features of the DEND syndrome include developmental delay, epilepsy and neonatal diabetes." ], "exact_answer": [ [ "developmental delay" ], [ "epilepsy" ], [ "neonatal diabetes" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "list", "id": "56c1f030ef6e39474100004d", "snippets": [ { "offsetInBeginSection": 116, "offsetInEndSection": 252, "text": "Some mutations in this gene, including p.Q52R, are associated with the developmental delay, epilepsy, neonatal diabetes (DEND) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24150202", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 759, "text": "Developmental delay was noted on follow-up which raised the possibility of intermediate DEND syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23783767", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 436, "text": "We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 282, "text": "They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23462667", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 501, "text": " Wide phenotype variability is associated with single ABCC8 mutations, ranging from transient or permanent neonatal diabetes (ND) with or without developmental delay (DEND syndrome) to very mild phenotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22326206", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 353, "text": "Specific uncommon mutations KCNJ11give rise to a syndrome defined as developmental delay, epilepsy, and neonatal diabetes (DEND), or - more frequently - to a milder sub-type lacking epilepsy, denoted as intermediate-DEND (iDEND).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22694282", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 756, "text": "Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768671", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 664, "text": " The patient with the V59M mutation successfully switched from insulin injections to oral glibenclamide; 2 years of follow-up revealed that the patient had intermediate developmental delay, epilepsy and neonatal diabetes (DEND) syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22145471", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 1078, "text": "Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768671", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 646, "text": "We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 939, "text": "There is a striking genotype-phenotype relationship with specific Kir6.2 mutations being associated with transient neonatal diabetes, permanent neonatal diabetes alone, and a novel syndrome characterized by developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16123337", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 427, "text": "In a few patients, KCNJ11 mutations cause a triad of developmental delay, epilepsy, and neonatal diabetes (DEND syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169493", "endSection": "title" }, { "offsetInBeginSection": 383, "offsetInEndSection": 658, "text": "It is proposed that some patients with KCNJ11 mutations have neurological features that are part of a discrete neurological syndrome termed developmental Delay, Epilepsy and Neonatal Diabetes (DEND), but there are also neurological consequences of chronic or acute diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16670688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15-yr-old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19686306", "endSection": "title" }, { "offsetInBeginSection": 184, "offsetInEndSection": 306, "text": "In a few patients, KCNJ11 mutations cause a triad of developmental delay, epilepsy, and neonatal diabetes (DEND syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652641", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 435, "text": "We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 657, "text": "It is proposed that some patients with KCNJ11 mutations have neurological features that are part of a discrete neurological syndrome termed developmental Delay, Epilepsy and Neonatal Diabetes (DEND), but there are also neurological consequences of chronic or acute diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16670688", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1466, "text": "We report a case of developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome that shows neurologic improvement with sulfonylurea therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652641", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 692, "text": "Some patients have DEND syndrome (developmental delay, epilepsy and neonatal diabetes) with the neurological features arising from mutated KATP channels in muscle, nerve and brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16019717", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 755, "text": "Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768671", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 574, "text": "Intermediate developmental delay, epilepsy and neonatal diabetes mellitus (DEND) syndrome as a result of a 59V>M Kir6.2 mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20368737", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1435, "text": "Five patients with developmental delay, epilepsy and neonatal diabetes (DEND) syndrome had unique mutations not associated with other phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16609879", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 756, "text": "Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768671", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 520, "text": "We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene. Thus, our case reinforces that most cases with DEND syndrome are insensitive to SU.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 693, "text": "Some patients have DEND syndrome (developmental delay, epilepsy and neonatal diabetes) with the neurological features arising from mutated KATP channels in muscle, nerve and brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16019717", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 436, "text": "We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 658, "text": "It is proposed that some patients with KCNJ11 mutations have neurological features that are part of a discrete neurological syndrome termed developmental Delay, Epilepsy and Neonatal Diabetes (DEND), but there are also neurological consequences of chronic or acute diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16670688", "endSection": "abstract" } ] }, { "body": "What is the RESID database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12520062", "http://www.ncbi.nlm.nih.gov/pubmed/15174122", "http://www.ncbi.nlm.nih.gov/pubmed/9847179", "http://www.ncbi.nlm.nih.gov/pubmed/11125090", "http://www.ncbi.nlm.nih.gov/pubmed/10592227" ], "ideal_answer": [ "The RESID Database of Protein Modifications is a comprehensive collection of annotations and structures for protein modifications and cross-links including pre-, co-, and post-translational modifications" ], "exact_answer": [ "The RESID Database of Protein Modifications is a comprehensive collection of annotations and structures for protein modifications and cross-links including pre-, co-, and post-translational modifications" ], "type": "factoid", "id": "5708992ccf1c32585100000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The RESID Database of Protein Modifications as a resource and annotation tool.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15174122", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The RESID Database of Protein Modifications is a comprehensive collection of annotations and structures for protein modifications and cross-links including pre-, co-, and post-translational modifications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15174122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "The RESID Database is a comprehensive collection of annotations and structures for protein pre-, co- and post-translational modifications including amino-terminal, carboxyl-terminal and peptide chain cross-link modifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The RESID Database is a comprehensive collection of annotations and structures for protein post-translational modifications including N-terminal, C-terminal and peptide chain cross-link modifications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11125090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The RESID Database contains supplemental information on post-translational modifications for the standardized annotations appearing in the PIR-International Protein Sequence Database. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10592227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "The RESID Database of protein structure modifications.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9847179", "endSection": "title" } ] }, { "body": "Pridopidine has been tested for treatment of which disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23446684", "http://www.ncbi.nlm.nih.gov/pubmed/21586914", "http://www.ncbi.nlm.nih.gov/pubmed/20667452", "http://www.ncbi.nlm.nih.gov/pubmed/20616707", "http://www.ncbi.nlm.nih.gov/pubmed/22948856", "http://www.ncbi.nlm.nih.gov/pubmed/22071279", "http://www.ncbi.nlm.nih.gov/pubmed/22560595", "http://www.ncbi.nlm.nih.gov/pubmed/23450660", "http://www.ncbi.nlm.nih.gov/pubmed/23468085", "http://www.ncbi.nlm.nih.gov/pubmed/20373247" ], "ideal_answer": [ "Pridopidine is a dopaminergic stabilizer that has shown promising results for treatment of Huntington disease patients." ], "exact_answer": [ "Huntington disease" ], "type": "factoid", "id": "550ea8f1b305b40c5c000005", "snippets": [ { "offsetInBeginSection": 1892, "offsetInEndSection": 2083, "text": "These effects of pridopidine may serve to strengthen the cortico-striatal communication and to improve motor control in Huntington's disease for which pridopidine is currently in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23468085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450660", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "We examined the effects of 3 dosages of pridopidine, a dopamine-stabilizing compound, on motor function and other features of Huntington's disease, with additional evaluation of its safety and tolerability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450660", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1497, "text": "Although the primary analysis did not demonstrate a statistically significant treatment effect, the overall results suggest that pridopidine may improve motor function in Huntington's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "One-year safety and tolerability profile of pridopidine in patients with Huntington disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446684", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "OBJECTIVE: To assess the 1-year safety profile of the dopaminergic stabilizer pridopidine in patients with Huntington disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446684", "endSection": "abstract" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1616, "text": "CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that pridopidine (\u226490 mg/day) is generally safe and well-tolerated in patients with Huntington disease for up to 1 year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Pridopidine is being developed for the treatment of impaired motor function associated with Huntington's disease and belongs to a new class of compounds known as dopidines, which act as dopaminergic stabilizers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22948856", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 431, "text": " There is so far neither cure nor approved disease-slowing therapy for HD, though recent clinical studies have shown a beneficial long-term effect of pridopidine in patients with HD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22560595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22071279", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 652, "text": "Pridopidine belongs to a new class of compounds known as dopaminergic stabilisers, and results from a small phase 2 study in patients with Huntington's disease suggested that this drug might improve voluntary motor function. We aimed to assess further the effects of pridopidine in patients with Huntington's disease. METHODS: We undertook a 6 month, randomised, double-blind, placebo-controlled trial to assess the efficacy of pridopidine in the treatment of motor deficits in patients with Huntington's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22071279", "endSection": "abstract" }, { "offsetInBeginSection": 2432, "offsetInEndSection": 2725, "text": "INTERPRETATION: This study did not provide evidence of efficacy as measured by the mMS, but a potential effect of pridopidine on the motor phenotype of Huntington's disease merits further investigation. Pridopidine up to 90 mg per day was well tolerated in patients with Huntington's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22071279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Regional cerebral glucose metabolism after pridopidine (ACR16) treatment in patients with Huntington disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21586914", "endSection": "title" }, { "offsetInBeginSection": 221, "offsetInEndSection": 748, "text": "Pridopidine (ACR16) belongs to a novel class of central nervous system compounds in development for the treatment of Huntington disease. The objective of the study was to investigate the metabolic changes in patients with Huntington disease before and after pridopidine treatment. METHODS: [(18)F]Fluorodeoxyglucose positron emission tomographic imaging was used to measure the regional cerebral metabolic rate of glucose at baseline and after 14 days of open-label pridopidine treatment in 8 patients with Huntington disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21586914", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1562, "text": "CONCLUSIONS: Our findings suggest that pridopidine induces metabolic changes in brain regions implicated as important for mediating compensatory mechanisms in Huntington disease. In addition, the finding of a strong relationship between clinical severity and metabolic activity after treatment also suggests that pridopidine treatment targets a Huntington disease-related metabolic activity pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21586914", "endSection": "abstract" }, { "offsetInBeginSection": 1365, "offsetInEndSection": 1574, "text": "The putative restoration of function in cortico-subcortical circuitry by pridopidine is likely to make it useful for ameliorating several neurological and psychiatric disorders, including Huntington's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20667452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Efficacy and safety of the dopaminergic stabilizer Pridopidine (ACR16) in patients with Huntington's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616707", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "OBJECTIVES: To evaluate the efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington's disease (HD). METHODS: In a randomized, double-blind, placebo-controlled, 4-week trial, patients with HD received pridopidine (50 mg/d, n = 28) or placebo (n = 30). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616707", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1237, "text": "CONCLUSIONS: Pridopidine shows promise as a treatment for some of the symptoms of HD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616707", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 841, "text": "Investigational drugs discussed include ALN-HTT (Alnylam Pharmaceuticals Inc/Medtronic Inc), EPI-743 (Edison Pharmaceuticals Inc), LNK-754 (Link Medicine Corp) and pridopidine (NeuroSearch A/S).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20373247", "endSection": "abstract" }, { "offsetInBeginSection": 1869, "offsetInEndSection": 2061, "text": "These effects of pridopidine may serve to strengthen the cortico-striatal communication and to improve motor control in Huntington's disease for which pridopidine is currently in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23468085", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1508, "text": "In addition, the finding of a strong relationship between clinical severity and metabolic activity after treatment also suggests that pridopidine treatment targets a Huntington disease-related metabolic activity pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21586914", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1181, "text": "Pridopidine shows promise as a treatment for some of the symptoms of HD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Pridopidine shows promise as a treatment for some of the symptoms of HD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616707", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 386, "text": "In addition, the finding of a strong relationship between clinical severity and metabolic activity after treatment also suggests that pridopidine treatment targets a Huntington disease-related metabolic activity pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21586914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "We examined the effects of 3 dosages of pridopidine, a dopamine-stabilizing compound, on motor function and other features of Huntington's disease, with additional evaluation of its safety and tolerability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450660", "endSection": "abstract" }, { "offsetInBeginSection": 1891, "offsetInEndSection": 2081, "text": "These effects of pridopidine may serve to strengthen the cortico-striatal communication and to improve motor control in Huntington's disease for which pridopidine is currently in development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23468085", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1522, "text": "In addition, the finding of a strong relationship between clinical severity and metabolic activity after treatment also suggests that pridopidine treatment targets a Huntington disease-related metabolic activity pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21586914", "endSection": "abstract" } ] }, { "body": "Are there currently applications of deep learning in genomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25948244", "http://www.ncbi.nlm.nih.gov/pubmed/24931975" ], "ideal_answer": [ "Yes. Deep learning has been used so far in genomics for predicting splicing patterns in individual tissues and differences in splicing patterns across tissues. The deep architecture surpasses the performance of the previous Bayesian method for predicting alternative splicing (AS) patterns." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281" ], "type": "yesno", "id": "56b481348525abca1e000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Deep learning of the tissue-regulated splicing code.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931975", "endSection": "title" }, { "offsetInBeginSection": 385, "offsetInEndSection": 826, "text": "Using a deep neural network, we developed a model inferred from mouse RNA-Seq data that can predict splicing patterns in individual tissues and differences in splicing patterns across tissues. Our architecture uses hidden variables that jointly represent features in genomic sequences and tissue types when making predictions. A graphics processing unit was used to greatly reduce the training time of our models with millions of parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931975", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1214, "text": "We show that the deep architecture surpasses the performance of the previous Bayesian method for predicting AS patterns. With the proper optimization procedure and selection of hyperparameters, we demonstrate that deep architectures can be beneficial, even with a moderately sparse dataset. An analysis of what the model has learned in terms of the genomic features is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Machine learning applications in genetics and genomics", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25948244", "endSection": "title" } ] }, { "body": "Are CpG islands located close to housekeeping genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15784181", "http://www.ncbi.nlm.nih.gov/pubmed/16474211", "http://www.ncbi.nlm.nih.gov/pubmed/15546139", "http://www.ncbi.nlm.nih.gov/pubmed/1968658", "http://www.ncbi.nlm.nih.gov/pubmed/3186440", "http://www.ncbi.nlm.nih.gov/pubmed/17591602", "http://www.ncbi.nlm.nih.gov/pubmed/8128314", "http://www.ncbi.nlm.nih.gov/pubmed/1505946", "http://www.ncbi.nlm.nih.gov/pubmed/3656447", "http://www.ncbi.nlm.nih.gov/pubmed/9632720", "http://www.ncbi.nlm.nih.gov/pubmed/9990116" ], "ideal_answer": [ "Our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated. These regions represent about 1% of genomic DNA and are generally found in the promoter region of housekeeping genes. In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island. Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences. All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands. It has been envisaged that CpG islands are often observed near the transcriptional start sites (TSS) of housekeeping genes. CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes. CpG islands were associated with the 5' ends of all housekeeping genes and many tissue-specific genes, and with the 3' ends of some tissue-specific genes. ", "Yes, CpG islands are preferentially located at the start of transcription of housekeeping genes and are associated with tissue-specific genes.", "These regions represent about 1% of genomic DNA and are generally found in the promoter region of housekeeping genes. Our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated. In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island. Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences. All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands. It has been envisaged that CpG islands are often observed near the transcriptional start sites (TSS) of housekeeping genes. CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes. CpG islands were associated with the 5' ends of all housekeeping genes and many tissue-specific genes, and with the 3' ends of some tissue-specific genes. " ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006796", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020043" ], "type": "yesno", "id": "5133b15e5274a5fb0700000b", "snippets": [ { "offsetInBeginSection": 1048, "offsetInEndSection": 1164, "text": "our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591602", "endSection": "sections.0" }, { "offsetInBeginSection": 236, "offsetInEndSection": 372, "text": "CpG islands are preferentially located at the start of transcription of housekeeping genes and are associated with tissue-specific genes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16474211", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "It has been envisaged that CpG islands are often observed near the transcriptional start sites (TSS) of housekeeping genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15784181", "endSection": "sections.0" }, { "offsetInBeginSection": 411, "offsetInEndSection": 528, "text": "These regions represent about 1% of genomic DNA and are generally found in the promoter region of housekeeping genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15546139", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "CpG islands are stretches of DNA sequence that are enriched in the (CpG)n repeat and are present in close association with all housekeeping genes as well as some tissue-specific genes in the mammalian genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9990116", "endSection": "sections.0" }, { "offsetInBeginSection": 225, "offsetInEndSection": 308, "text": "CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9632720", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8128314", "endSection": "sections.0" }, { "offsetInBeginSection": 496, "offsetInEndSection": 689, "text": "All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1505946", "endSection": "sections.0" }, { "offsetInBeginSection": 103, "offsetInEndSection": 319, "text": "Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1968658", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Unmethylated CpG rich islands are a feature of vertebrate DNA: they are associated with housekeeping and many tissue specific genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3186440", "endSection": "sections.0" }, { "offsetInBeginSection": 548, "offsetInEndSection": 702, "text": "CpG islands were associated with the 5' ends of all housekeeping genes and many tissue-specific genes, and with the 3' ends of some tissue-specific genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3656447", "endSection": "sections.0" } ] }, { "body": "Is COL5A2 gene associated to ischemic heart disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23574622" ], "ideal_answer": [ "Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease ", "In a gene co-expression network from microarray data originating from a mouse model of myocardial infraction, Col5a2 shows predictive potential, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3394", "http://www.uniprot.org/uniprot/CO5A2_HUMAN", "http://www.uniprot.org/uniprot/CO5A2_MOUSE" ], "type": "yesno", "id": "54e12c30ae9738404b000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574622", "endSection": "title" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1148, "text": "Col5a2, a gene previously not specifically linked to MI response but responsible for the classic type of Ehlers-Danlos syndrome, was found to have many and strong co-expression associations within this community", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574622", "endSection": "abstract" }, { "offsetInBeginSection": 1648, "offsetInEndSection": 1816, "text": "Col5a2 shows predictive potential in MI, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574622", "endSection": "title" } ] }, { "body": "Which is the target of bortezomib used in cancer therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22037302", "http://www.ncbi.nlm.nih.gov/pubmed/16034054", "http://www.ncbi.nlm.nih.gov/pubmed/23822887", "http://www.ncbi.nlm.nih.gov/pubmed/14695130", "http://www.ncbi.nlm.nih.gov/pubmed/20616904", "http://www.ncbi.nlm.nih.gov/pubmed/16258456", "http://www.ncbi.nlm.nih.gov/pubmed/23055533", "http://www.ncbi.nlm.nih.gov/pubmed/19037995", "http://www.ncbi.nlm.nih.gov/pubmed/21862633", "http://www.ncbi.nlm.nih.gov/pubmed/18347166", "http://www.ncbi.nlm.nih.gov/pubmed/22204764", "http://www.ncbi.nlm.nih.gov/pubmed/14688465", "http://www.ncbi.nlm.nih.gov/pubmed/21824109", "http://www.ncbi.nlm.nih.gov/pubmed/19164757", "http://www.ncbi.nlm.nih.gov/pubmed/22819849", "http://www.ncbi.nlm.nih.gov/pubmed/22057347", "http://www.ncbi.nlm.nih.gov/pubmed/17197231", "http://www.ncbi.nlm.nih.gov/pubmed/18491989", "http://www.ncbi.nlm.nih.gov/pubmed/15846112", "http://www.ncbi.nlm.nih.gov/pubmed/18205878", "http://www.ncbi.nlm.nih.gov/pubmed/17504161", "http://www.ncbi.nlm.nih.gov/pubmed/17591945", "http://www.ncbi.nlm.nih.gov/pubmed/15687646", "http://www.ncbi.nlm.nih.gov/pubmed/21242725" ], "ideal_answer": [ "Bortezomib is a potent and specific reversible ubiquitin/proteasome pathway inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies." ], "exact_answer": [ "The ubiquitin/proteasome pathway" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058990", "http://www.biosemantics.org/jochem#4241338" ], "type": "factoid", "id": "5319a708b166e2b806000024", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 543, "text": "The ubiquitin-proteasome system (UPS) degrades 80 - 90% of intracellular proteins. Cancer cells take advantage of the UPS for their increased growth and decreased apoptotic cell death. Thus, the components that make up the UPS represent a diverse group of potential anti-cancer targets. The success of the first-in-class proteasome inhibitor bortezomib not only proved that the proteasome is a feasible and valuable anti-cancer target, but also inspired researchers to extensively explore other potential targets of this pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23822887", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 314, "text": "The ubiquitin-proteasome pathway has been identified as a potential molecular target for cancer therapy. In this study, we investigated the effect of the proteasome inhibitor bortezomib on anaplastic thyroid carcinoma (ATC) characterized by complete refractoriness to multimodal therapeutic approaches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "The ubiquitin-proteasome pathway regulates many basic cellular processes and has been proven to be a promising target for cancer therapy. Bortezomib is the first U.S. Food and Drug Administration (FDA) approved proteasome inhibitor used in the treatment of newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, and mantle cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22204764", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1785, "text": "This review summarizes the current status of bortezomib as well as several other proteasome inhibitors that are currently under clinical and preclinical investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22204764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment of multiple myeloma validated the 20S core particle as an anticancer drug target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22057347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The ubiquitin-proteasome system (UPS) is a conserved pathway regulating numerous biological processes including protein turnover, DNA repair, and intracellular trafficking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819849", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 531, "text": "The development of bortezomib (Velcade(\u00ae)) as a treatment for multiple myeloma and mantle cell lymphoma has verified this and suggests that targeting other components of the UPS may be a viable strategy for the treatment for cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819849", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1668, "text": "The proteasome inhibitor bortezomib is now in the clinic to treat multiple myeloma and mantle cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22037302", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 727, "text": "In this study, we investigated the transcriptome-wide effects of the proteasome inhibitor bortezomib on estrogen-regulated transcription in MCF7 human breast cancer cells and showed that bortezomib caused a specific global decrease in estrogen-induced gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862633", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1202, "text": "The clinical efficacy of the proteasome inhibitor bortezomib toward multiple myeloma and other hematologic malignancies provides the \"proof of concept\" that targeting the proteasome is a promising strategy for cancer treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21824109", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 1231, "text": "It has previously been suggested that the excess proteins not targeted to the proteasome, or that accumulate when the proteasome is inhibited through the use of chemically active agents such as bortezomib, are linked to impaired cell survival, and that their packaging in the form of an aggresome somehow minimizes their 'proteotoxicity' allowing these toxic proteins to be sequestered away from normal cellular machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21242725", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 214, "text": "The proteasome inhibitor bortezomib has clinical activity in multiple myeloma and mantle cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19164757", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 485, "text": "Bortezomib (PS-341) is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616904", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 1067, "text": "In addition to the development and clinical validation of proteasome inhibitor, bortezomib, in myeloma therapy, recent studies have demonstrated that it is possible to develop inhibitors for specific ubiquitination and deubiquitination enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19037995", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 931, "text": "Bortezomib as first-in-class proteasome inhibitor has proven to be highly effective in some hematological malignancies, overcomes conventional chemoresistance, directly induces cell cycle arrest and apoptosis, and also targets the tumor microenvironment. It has been granted approval by the FDA for relapsed multiple myeloma, and recently for relapsed mantle cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18491989", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 903, "text": "Validation of the ubiquitin-proteasome pathway as a target for cancer therapy has come in the form of approvals of the first such inhibitor, bortezomib, for relapsed/refractory multiple myeloma and mantle cell lymphoma, for which this agent has become a standard of care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347166", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 853, "text": "Cells were cultured, exposed to proteasome inhibitors (bortezomib, ALLN, MG-132 and epoxomicin) and then assayed for cell cycle and cell death analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18205878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The proteasome has emerged as an important target for cancer therapy with the approval of bortezomib, a first-in-class, reversible proteasome inhibitor, for relapsed/refractory multiple myeloma (MM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591945", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 437, "text": "Bortezomib is the first proteasome inhibitor to enter clinical use, and received approval by the Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma, therefore validating inhibition of the proteasome as an anticancer target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17504161", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 573, "text": "Bortezomib (Velcade, PS-341) was the first proteasome inhibitor to receive regulatory approval from the US Food and Drug Administration for the treatment of multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17197231", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1213, "text": "Preclinical evidence using bortezomib, the only proteasome inhibitor to enter clinical trials, suggests that proteasome inhibition may be effective in the treatment of hematologic and solid malignancies by promoting apoptosis, retarding angiogenesis, and inhibiting tumor cell adhesion and production of growth factors by acting on molecules such as nuclear factor-kappaB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258456", "endSection": "abstract" }, { "offsetInBeginSection": 1380, "offsetInEndSection": 1584, "text": "Bortezomib was recently approved for the treatment of multiple myeloma. It is currently being investigated, both as a single agent and in combination, in phase I and II trials in a variety of tumor types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258456", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1221, "text": "Protein degradation pathways are also targets for cancer therapy, as shown by the successful introduction of bortezomib, an inhibitor of the 26S proteasome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034054", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1467, "text": "Bortezomib is the first proteasome inhibitor that has entered clinical trials. In multiple myeloma, both the US Food and Drug Administration and European Medicine Evaluation Agency granted approval for the use of bortezomib (Velcade) for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15846112", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 835, "text": "The potent and selective proteasome inhibitor bortezomib (VELCADE; formerly known as PS-341) is particularly promising as a potential anticancer agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687646", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 1097, "text": "Inhibitors of the proteasome impact on cells in part through down-regulation of nuclear factor kappaB, but also through modulation of cell cycle proteins and other pro- and antiapoptotic pathways. Bortezomib (VELCADE; formerly PS-341), the first such inhibitor to undergo clinical testing, has demonstrated impressive antitumor activity and manageable toxicities in Phase I and II trials both as a single agent, and in combination with other drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14695130", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1726, "text": "Although targeting E3 ubiquitin ligases is still in its infancy, speedy approval of the general proteasome inhibitor, Velcade (bortezomib) by the FDA for the treatment of relapsed and refractory multiple myeloma suggests the promise of specific E3 inhibitors in anti-cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14688465", "endSection": "abstract" } ] }, { "body": "Have microRNAs been implicated in pharmacogenomics? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22909203", "http://www.ncbi.nlm.nih.gov/pubmed/21412770", "http://www.ncbi.nlm.nih.gov/pubmed/20585341", "http://www.ncbi.nlm.nih.gov/pubmed/18187804", "http://www.ncbi.nlm.nih.gov/pubmed/22445829", "http://www.ncbi.nlm.nih.gov/pubmed/21047203", "http://www.ncbi.nlm.nih.gov/pubmed/16854228", "http://www.ncbi.nlm.nih.gov/pubmed/22630332", "http://www.ncbi.nlm.nih.gov/pubmed/21499217", "http://www.ncbi.nlm.nih.gov/pubmed/23376192", "http://www.ncbi.nlm.nih.gov/pubmed/23189953", "http://www.ncbi.nlm.nih.gov/pubmed/17483436" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/12052143", "o": "http://purl.uniprot.org/pubmed/12052143" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/15584875", "o": "Pharmacogenomics" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/16886893", "o": "http://purl.uniprot.org/pubmed/16886893" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/16981842", "o": "Pharmacogenomics" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/17638511", "o": "Pharmacogenomics" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/17391071", "o": "http://purl.uniprot.org/pubmed/17391071" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/17716225", "o": "http://purl.uniprot.org/pubmed/17716225" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/17979512", "o": "Pharmacogenomics" } ], "ideal_answer": [ "Yes. MicroRNAs have been implicated in pharmacogenomics." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010597", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "yesno", "id": "5162a089298dcd4e51000043", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 435, "text": "A major discovery is the ability of miRNAs to determine the efficacy of drugs, which has given rise to the field of 'miRNA pharmacogenomics' through 'Pharmaco-miRs'. miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376192", "endSection": "sections.0" }, { "offsetInBeginSection": 878, "offsetInEndSection": 1199, "text": "The potential modulation of toxicology-related changes in miRNA expression, the role of miRNA in immune-mediated drug-induced liver injuries, the use of circulating miRNAs in body fluids as potential toxicological biomarkers, and the link between miRNA-related pharmacogenomics and adverse drug reactions are highlighted.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23189953", "endSection": "sections.0" }, { "offsetInBeginSection": 232, "offsetInEndSection": 531, "text": "Single nucleotide polymorphisms (SNPs) in the miRNA target sequences may affect or impair the binding of miRNAs. Studies have shown that SNPs in miRNA target sites (miR-TS-SNPs) have a great influence on diverse biological functions, including pharmacogenomics and disease susceptibilities in human.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445829", "endSection": "sections.0" }, { "offsetInBeginSection": 454, "offsetInEndSection": 782, "text": "Pharmacogenomics genes can be divided into drug target genes termed as pharmacodynamics genes (PD) and genes involved in drug transport and metabolism termed as pharmacokinetics genes (PK). To clarify the regulatory potential of miRNAs in pharmacogenomics, we have examined the potential regulation by miRNAs of PK and PD genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21499217", "endSection": "sections.0" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1786, "text": "Our analysis identify a striking difference in the level of miRNA regulation between PK and PD genes, with the former having less than half predicted conserved miRNA binding sites compared with the latter. Importantly, this finding is reflected in a highly significant difference in the shift in expression levels of PD versus PK genes after depletion of miRNAs. CONCLUSIONS: Our study emphasizes an intrinsic difference between PK and PD genes and helps clarify the role of miRNAs in pharmacogenomics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21499217", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 419, "text": "Pharmacogenomics, toxicogenomics, and small RNA expression analysis are three of the most active research topics in the biological, biomedical, pharmaceutical, and toxicological fields. All of these studies are based on gene expression analysis, which requires reference genes to reduce the variations derived from different amounts of starting materials and different efficiencies of RNA extraction and cDNA synthesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21412770", "endSection": "sections.0" }, { "offsetInBeginSection": 2269, "offsetInEndSection": 2426, "text": "In contrast, hTBCA and small RNAs are more stable during drug treatment, and they are better reference genes for pharmacogenomics and toxicogenomics studies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21412770", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 152, "text": "Polymorphisms of genes involved in the pharmacokinetic and pharmacodynamic processes underlie the divergent drug responses among individuals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047203", "endSection": "sections.0" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1167, "text": "A panel of drug-response genes was constructed, which contains 923 pharmacokinetic genes, 703 pharmacodynamic genes and 720 miRNAs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047203", "endSection": "sections.0" }, { "offsetInBeginSection": 123, "offsetInEndSection": 243, "text": "miRNA variations can affect drug resistance, efficacy, and metabolism, opening new avenues of pharmacogenomics research.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20585341", "endSection": "sections.0" }, { "offsetInBeginSection": 260, "offsetInEndSection": 467, "text": "we studied the pharmacologic roles of three microRNAs previously implicated in cancer biology (let-7i, mir-16, and mir-21) and also used in silico methods to test pharmacologic microRNA effects more broadly.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18187804", "endSection": "sections.0" }, { "offsetInBeginSection": 1322, "offsetInEndSection": 1781, "text": "n silico comparison of drug potencies with microRNA expression profiles across the entire NCI-60 panel revealed that approximately 30 microRNAs, including mir-21, show highly significant correlations with numerous anticancer agents. Ten of those microRNAs have already been implicated in cancer biology. Our results support a substantial role for microRNAs in anticancer drug response, suggesting novel potential approaches to the improvement of chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18187804", "endSection": "sections.0" }, { "offsetInBeginSection": 392, "offsetInEndSection": 603, "text": "The NCI-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17483436", "endSection": "sections.0" }, { "offsetInBeginSection": 738, "offsetInEndSection": 941, "text": "To complement the existing NCI-60 data sets, we have measured expression levels of microRNAs in the NCI-60 and incorporated the resulting data into the CellMiner program package for integrative analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17483436", "endSection": "sections.0" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1765, "text": ". Comparison of microRNA expression patterns and compound potency patterns showed significant correlations, suggesting that microRNAs may play a role in chemoresistance. Combined with gene expression and other biological data using multivariate analysis, microRNA expression profiles may provide a critical link for understanding mechanisms involved in chemosensitivity and chemoresistance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17483436", "endSection": "sections.0" }, { "offsetInBeginSection": 296, "offsetInEndSection": 364, "text": "This study reports on miRNAs implicated in SSRI sensitivity of LCLs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22909203", "endSection": "sections.0" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1071, "text": "these miRNAs as tentative SSRI response biomarkers awaits validation with lymphocyte samples of major depression patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22909203", "endSection": "sections.0" } ] }, { "body": "Which genes are known to be involved in Diamond-Blackfan anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22689679", "http://www.ncbi.nlm.nih.gov/pubmed/22706301", "http://www.ncbi.nlm.nih.gov/pubmed/23257444", "http://www.ncbi.nlm.nih.gov/pubmed/18715690", "http://www.ncbi.nlm.nih.gov/pubmed/20378560", "http://www.ncbi.nlm.nih.gov/pubmed/22262766", "http://www.ncbi.nlm.nih.gov/pubmed/19773262", "http://www.ncbi.nlm.nih.gov/pubmed/20454576", "http://www.ncbi.nlm.nih.gov/pubmed/20655265", "http://www.ncbi.nlm.nih.gov/pubmed/23812780" ], "ideal_answer": [ "Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents during the first year of life. The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26, as well as in GATA1, in about 60-65 % of patients." ], "exact_answer": [ [ "RPS19" ], [ "RPS24" ], [ "RPS17" ], [ "RPL35A" ], [ "RPL5" ], [ "RPL11" ], [ "RPS7" ], [ "RPS10" ], [ "RPS26" ], [ "RPL26" ], [ "GATA1" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1339" ], "type": "list", "id": "550312b4e9bde6963400001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 645, "text": "Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents during the first year of life. The main features of the disease are normochromic and macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. The patients also present with growth retardation and craniofacial, upper limb, heart and urinary system congenital malformations in ~30-50 % of cases. The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23812780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "This study was aimed to explore the mutations of ribosomal protein (RP) genes in patients with Diamond Blackfan anemia (DBA). Twenty-one cases of DBA admitted in our hospital from Dec 2008 to Aug 2012 were screened by PCR for mutations in the nine known genes associated with DBA: RPS19, RPS24, RPS17, RPL5, RPL11, RPS7, RPL35a, RPS10 and RPS26", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257444", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 602, "text": "The results found that 8 patients (38.1%) with DBA had mutations in the genes coding for ribosomal protein, in which RPS19 mutation was identified in 3 patients, RPS24, RPS7, RPL5, RPL11 and RPL35A mutations were identified respectively in 1 of the patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Diamond-Blackfan anemia (DBA) is a hypoplastic anemia characterized by impaired production of red blood cells, with approximately half of all cases attributed to ribosomal protein gene mutations. We performed exome sequencing on two siblings who had no known pathogenic mutations for DBA and identified a mutation in the gene encoding the hematopoietic transcription factor GATA1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22706301", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 679, "text": "As a proof of concept, we designed a multiplex ligation-dependent probe amplification assay targeted to screen the six genes that are most frequently mutated in Diamond-Blackfan anemia patients: RPS17, RPS19, RPS26, RPL5, RPL11, and RPL35A. Using this assay we showed that deletions represent approximately 20% of all mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22689679", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 658, "text": "DESIGN AND METHODS: We screened 49 Japanese patients with Diamond-Blackfan anemia (45 probands) for mutations in the six known genes associated with Diamond-Blackfan anemia: RPS19, RPS24, RPS17, RPL5, RPL11, and RPL35A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378560", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 492, "text": "Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19773262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "OBJECTIVE: Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia caused by mutations in ribosomal protein (RP) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18715690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22262766", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 429, "text": "Mutations in the gene coding for the ribosomal protein RPS19 have been identified in 25% of patients with DBA, with resulting impairment of 18S rRNA processing and 40S ribosomal subunit formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20454576", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 626, "text": "We screened 49 Japanese patients with Diamond-Blackfan anemia (45 probands) for mutations in the six known genes associated with Diamond-Blackfan anemia: RPS19, RPS24, RPS17, RPL5, RPL11, and RPL35A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378560", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 479, "text": "Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19773262", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 855, "text": "The first ribosomal gene involved in DBA, ribosomal protein (RP) gene S19 (RPS19 gene), was identified in 1999", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20655265", "endSection": "abstract" }, { "offsetInBeginSection": 1260, "offsetInEndSection": 1396, "text": "These data identify RPL15 as a new gene involved in DBA and further support the presence of large deletions in RP genes in DBA patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23812780", "endSection": "abstract" } ] }, { "body": "Is nicotinamide effective for skin cancer prevention?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25561219", "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "http://www.ncbi.nlm.nih.gov/pubmed/24798949", "http://www.ncbi.nlm.nih.gov/pubmed/19804594", "http://www.ncbi.nlm.nih.gov/pubmed/23349012" ], "ideal_answer": [ "Yes, oral nicotinamide is safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012878", "http://www.disease-ontology.org/api/metadata/DOID:3451", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4273660", "http://www.biosemantics.org/jochem#4273660", "http://www.disease-ontology.org/api/metadata/DOID:4159" ], "type": "yesno", "id": "56c03d1fef6e39474100001a", "snippets": [ { "offsetInBeginSection": 174, "offsetInEndSection": 341, "text": "Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1820, "text": "ESULTS: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract" }, { "offsetInBeginSection": 2040, "offsetInEndSection": 2192, "text": "CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 281, "text": "Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798949", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1005, "text": " In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798949", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 385, "text": "Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349012", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 357, "text": "Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19804594", "endSection": "abstract" }, { "offsetInBeginSection": 1714, "offsetInEndSection": 1940, "text": "These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349012", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 611, "text": "Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349012", "endSection": "abstract" }, { "offsetInBeginSection": 1821, "offsetInEndSection": 2193, "text": "No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued.CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 612, "text": "Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.METHODS: In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1597, "text": "Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract" }, { "offsetInBeginSection": 2021, "offsetInEndSection": 2160, "text": "Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Nicotinamide has shown potential as a safe and effective intervention for the prevention of malignant and premalignant skin lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561219", "endSection": "abstract" }, { "offsetInBeginSection": 1749, "offsetInEndSection": 1853, "text": "Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19804594", "endSection": "abstract" } ] }, { "body": "Which is the chromosomal location of the gene MAOA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2906043" ], "ideal_answer": [ "The MAOA gene is locatad on chromosome X (Xp21-p11)." ], "exact_answer": [ "Xp21-p11" ], "concepts": [ "http://www.uniprot.org/uniprot/AOFA_CANFA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005694", "http://www.uniprot.org/uniprot/AOFA_BOVIN", "http://www.uniprot.org/uniprot/AOFA_PONAB", "http://www.uniprot.org/uniprot/AOFA_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051303", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002875", "http://www.uniprot.org/uniprot/AOFA_SHEEP", "http://www.uniprot.org/uniprot/AOFA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008123" ], "type": "factoid", "id": "56cf3f4f3975bb303a000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Human monoamine oxidase gene (MAOA): chromosome position (Xp21-p11) and DNA polymorphism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2906043", "endSection": "title" }, { "offsetInBeginSection": 440, "offsetInEndSection": 585, "text": " Using rodent-human somatic cell hybrids containing all or part of the human X chromosome, we have mapped these fragments to the region Xp21-p11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2906043", "endSection": "abstract" } ] }, { "body": "Do Parkinson's disease patients experience stridor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20205147", "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "http://www.ncbi.nlm.nih.gov/pubmed/12023429", "http://www.ncbi.nlm.nih.gov/pubmed/6622345", "http://www.ncbi.nlm.nih.gov/pubmed/7785431", "http://www.ncbi.nlm.nih.gov/pubmed/7651445", "http://www.ncbi.nlm.nih.gov/pubmed/10391085", "http://www.ncbi.nlm.nih.gov/pubmed/14703107", "http://www.ncbi.nlm.nih.gov/pubmed/19010952", "http://www.ncbi.nlm.nih.gov/pubmed/19628429", "http://www.ncbi.nlm.nih.gov/pubmed/21819188", "http://www.ncbi.nlm.nih.gov/pubmed/16575624", "http://www.ncbi.nlm.nih.gov/pubmed/12884831", "http://www.ncbi.nlm.nih.gov/pubmed/8353712" ], "ideal_answer": [ "Yes. Stridor has been described in Parkinon's disease patients. Stridor has been linked to deep brain stimulation and L-Dopa medication use. \nHowever, stridor was shown to be more common in multiple system atrophy patients." ], "exact_answer": "yes", "type": "yesno", "id": "54d8d4d1014675820d000006", "snippets": [ { "offsetInBeginSection": 381, "offsetInEndSection": 640, "text": "The authors describe a patient experiencing stridor and dysphagia with confirmed pulmonary restriction and aspiration following subthalamic nucleus deep brain stimulator adjustment, with a resolution of symptoms and signs when the stimulator was switched off.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21819188", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 596, "text": "Stridor was not noted during sleep at night. Endoscopic examination of the larynx revealed insufficient abduction of the bilateral vocal cords, although the glottis was not so small as to cause stridor during inspiration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14703107", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1064, "text": "The stridor was specific to MSA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575624", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 705, "text": "Patients with MSA can present other clinical features, such as inspiratory stridor and rapid eye movement (REM) sleep behaviour disorder (RBD). We report a patient with pathologically confirmed MSA who presented with a longstanding history of stridor, RBD and autonomic disturbances but did not develop overt parkinsonism or cerebellar signs. This case illustrates that MSA may present clinically without its cardinal motor symptoms, and that stridor and RBD may be clues to recognise the disease in a patient with autonomic failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19010952", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1214, "text": "Patients with PD did not display sleep hypoventilation, stridor and abnormal central sleep apnea. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19628429", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 678, "text": "DEVELOPMENT: Autonomic disorders such as seborrhoeic dermatitis and disorders involving sweating, fatigue, weight loss or respiratory problems (dyspnea, inspiratory stridor) are highly prevalent and very disabling symptoms. In addition, they may be the main problem in a particular phase of PD (fatigue, stridor) and condition the quality of life of patients with Parkinson. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205147", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 294, "text": ". Her dyspneic attacks consisting of inspiratory stridor and cyanosis occurred mainly during the wearing-off time and continued for less than 30 min", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12884831", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 873, "text": "The most commonly reported sleep disorders were sleep fragmentation (52.5%), vocalisation (60%), REM sleep behaviour disorder (47.5%), and nocturnal stridor (19%). Except for sleep fragmentation, the incidence of these disorders was significantly higher than in PD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12023429", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 644, "text": "Six days after admission, dyspnea and inspiratory stridor were noted, and the respiratory distress worsened. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10391085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "A patient is described with idiopathic Parkinson's disease and severe laryngeal stridor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6622345", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 392, "text": "The laryngeal stridor responded to levodopa therapy, and we are not aware that this has been reported previously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6622345", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1032, "text": "The subsequent clinical course of the former eight patients has been typical of idiopathic Parkinson's disease, whilst the ninth patient has developed postural hypotension, urinary incontinence and respiratory stridor typical of multiple system atrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8353712", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 907, "text": "Although each of five autonomic domains was affected in variable numbers of IPD patients, AD in MSA generally involved more autonomic domains than in IPD, and to a more severe degree, in particular with regard to inspiratory stridor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7785431", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1187, "text": "However, the presence of severe AD, of AD preceding parkinsonism, or of inspiratory stridor, are all individually suggestive of MSA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7785431", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 995, "text": "Apart from dysautonomia, the principal discriminant clinical features that distinguished SND from PD were the early appearance of the following symptoms and signs: (a) severe and atypical progressive parkinsonism characterized by bilateral bradykinesia and rigidity, slowness of gait, postural instability, and falls, and poor or absent response to adequate levodopa treatment; (b) increased tendon reflexes associated or not with frank pyramidal signs, severe dysarthria, and less consistently, dysphagia, stridor, antecollis, and stimulus-sensitive myoclonus, which, when present, are highly suggestive of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7651445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "OBJECTIVES: (1) To present a rare case of stridor secondary to prolonged laryngospasm in a patient with Parkinson's disease, and (2) to review the literature on stridor in Parkinson's disease. METHODS: We report a 73-year-old Parkinson's disease patient who developed acute stridor due to prolonged laryngospasm triggered by overspill of excessive secretions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 672, "text": "RESULT: Only 12 previously reported cases of stridor in Parkinson's disease patients were identified. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1328, "text": "This case emphasises the importance of recognising different causes of stridor in Parkinson's disease patients, as this affects management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 654, "text": "RESULT: Only 12 previously reported cases of stridor in Parkinsons disease patients were identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1305, "text": "This case emphasises the importance of recognising different causes of stridor in Parkinsons disease patients, as this affects management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "OBJECTIVES: (1) To present a rare case of stridor secondary to prolonged laryngospasm in a patient with Parkinsons disease, and (2) to review the literature on stridor in Parkinsons disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 356, "text": "METHODS: We report a 73-year-old Parkinsons disease patient who developed acute stridor due to prolonged laryngospasm triggered by overspill of excessive secretions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "(1) To present a rare case of stridor secondary to prolonged laryngospasm in a patient with Parkinson's disease, and (2) to review the literature on stridor in Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003593", "endSection": "abstract" } ] }, { "body": "Which depression rating scales were shown to have acceptable psychometric properties for screening of poststroke depression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18039246", "http://www.ncbi.nlm.nih.gov/pubmed/19074478", "http://www.ncbi.nlm.nih.gov/pubmed/23385849", "http://www.ncbi.nlm.nih.gov/pubmed/1410202", "http://www.ncbi.nlm.nih.gov/pubmed/12297607", "http://www.ncbi.nlm.nih.gov/pubmed/15387399", "http://www.ncbi.nlm.nih.gov/pubmed/18648195", "http://www.ncbi.nlm.nih.gov/pubmed/23167974" ], "ideal_answer": [ "The Center of Epidemiological Studies-Depression Scale, Hamilton Depression Rating Scale, and the Patient Health Questionnaire, The Beck Depression Inventory, Hospital Anxiety and Depression Scale-depression subscale, Montgomery-Asberg Depression Rating Scale, Poststroke Depression Rating Scale and Clinical Global Impression scale appeared to have acceptable psychometric properties for identifying depression in patients after stroke. Therefore, these scales can be used for screening of post-stroke depression. Signs of Depression Scale and Visual Analogue Mood Scale showed inferior psychometric properties and therefore should not be used for screening for post-stroke depression." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003865", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008403", "http://www.disease-ontology.org/api/metadata/DOID:3455", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003866", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011569", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020521" ], "type": "summary", "id": "51492168d24251bc05000041", "snippets": [ { "offsetInBeginSection": 704, "offsetInEndSection": 1157, "text": "The Center of Epidemiological Studies-Depression Scale (CESD) (sensitivity: 0.75; 95% CI 0.60 to 0.85; specificity: 0.88; 95% CI 0.71 to 0.95), the Hamilton Depression Rating Scale (HDRS) (sensitivity: 0.84; 95% CI 0.75 to 0.90; specificity:0.83; 95% CI 0.72 to 0.90) and the Patient Health Questionnaire (PHQ)-9 (sensitivity: 0.86; 95% CI 0.70 to 0.94; specificity: 0.79; 95% CI 0.60 to 0.90) appeared to be the optimal measures for screening measures.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385849", "endSection": "sections.0" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1385, "text": "There are a number of possible instruments that may help in screening for poststroke depression but none are satisfactory for case-finding.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385849", "endSection": "sections.0" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1470, "text": "Preliminary data suggests the CESD, HDRS or the PHQ-9 as the most promising options.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385849", "endSection": "sections.0" }, { "offsetInBeginSection": 424, "offsetInEndSection": 956, "text": "The Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale-depression subscale (HADS-D), Hamilton Rating Scale for Depression (HAMD), and Montgomery-Asberg Depression Rating Scale (MADRS) were administered. The balance of sensitivity and specificity was assessed using receiver operating characteristics (ROC) analysis. RESULTS: Discriminating abilities of all the scales for major and all PSD were good (area under ROC values 0.88-0.93 and 0.88-0.92 at 2 weeks; and 0.93-0.96 and 0.89-0.91 at 1 year, respectively).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23167974", "endSection": "sections.0" }, { "offsetInBeginSection": 277, "offsetInEndSection": 646, "text": "We compared the Beck Depression Inventory, Hamilton Rating Scale for Depression, Visual Analogue Mood Scale, proxy assessment, and Clinical Global Impression of the nursing and study personnel, together with Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised diagnosis, in assessing depression after stroke in a follow-up study of 100 patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074478", "endSection": "sections.0" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1325, "text": "The sensitivity and specificity against the Diagnostic and Statistical Manual of Mental Disorders criteria were acceptable with the Clinical Global Impression, Beck Depression Inventory, and Hamilton Rating Scale for Depression, mostly in the range of 0.70 to 1.00.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074478", "endSection": "sections.0" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 1668, "text": "The Visual Analogue Mood Scale was not a sensitive instrument (sensitivity, 0.20 to 0.60) and did not correlate with the Beck Depression Inventory during the first year after stroke.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074478", "endSection": "sections.0" }, { "offsetInBeginSection": 1682, "offsetInEndSection": 2015, "text": "Beck Depression Inventory, Hamilton Rating Scale for Depression, and Clinical Global Impression assessment by professionals, in addition to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised diagnosis, are useful in assessing depression, but none of these instruments clearly stood apart from the others.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074478", "endSection": "sections.0" }, { "offsetInBeginSection": 2016, "offsetInEndSection": 2187, "text": "Proxy ratings should be used with caution, and the use of the Visual Analogue Mood Scale among patients with aphasia and other cognitive impairments cannot be recommended.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074478", "endSection": "sections.0" }, { "offsetInBeginSection": 358, "offsetInEndSection": 590, "text": "This study evaluated the diagnostic accuracy of the Poststroke Depression Rating Scale (PSDRS), a diagnostic tool specifically devised to assess depression after stroke, in comparison to the Hamilton Depression Rating Scale (Ham-D).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648195", "endSection": "sections.0" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1199, "text": "At their optimum cut-off points, the Ham-D and PSDRS showed good sensitivity and specificity for MDL or MDL + MDDM; the PSDRS had a higher positive predictive value for MDL in respect of the Ham-D (78 vs. 59%).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648195", "endSection": "sections.0" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1305, "text": "Furthermore, the diagnostic accuracy of the PSDRS was higher in respect of the Ham-D in aphasic patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648195", "endSection": "sections.0" }, { "offsetInBeginSection": 1534, "offsetInEndSection": 1614, "text": "The Ham-D and PSDRS are both reliable diagnostic tools for the diagnosis of PSD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648195", "endSection": "sections.0" }, { "offsetInBeginSection": 1852, "offsetInEndSection": 1948, "text": "We suggest that the PSDRS could be a useful tool in clinical practice and in therapeutic trials.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648195", "endSection": "sections.0" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1573, "text": "The psychiatrist classified 25/71 (35.2%) patients as depressed. Using the recommended cut-point of 2 or more on the Signs of Depression Scale, the nurse and carer respectively rated 27/71 (38.0%) and 18/30 (60.0%) patients as potentially depressed. The proportion of patients correctly identified as depressed by the test (sensitivity) when rated by nurses was 64%, and the proportion of patients not depressed who were correctly identified by the test (specificity) was 61%, whereas carers achieved sensitivity 90% and specificity 35%.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18039246", "endSection": "sections.0" }, { "offsetInBeginSection": 1768, "offsetInEndSection": 2180, "text": "The Signs of Depression Scale is easily completed by clinical staff, although we found the sensitivity when completed by nurses to be low. Information from carers shows potential to improve screening and it is important for nurses to value the knowledge and skills of carers in detecting depression following a stroke. Further refinement of the Signs of Depression Scale, with accompanying research, is required.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18039246", "endSection": "sections.0" }, { "offsetInBeginSection": 743, "offsetInEndSection": 940, "text": "The VAMS was not useful in screening for depression in Chinese stroke patients while both the HADS and the GDS demonstrated satisfactory accuracy in detecting depression in Chinese stroke patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15387399", "endSection": "sections.0" }, { "offsetInBeginSection": 315, "offsetInEndSection": 578, "text": "At their respective optimum cutoff values, the sensitivity of the self-rated scales varied between 80% and 90%, while the specificity was about 60%. For the observer-rated scale (Hamilton Depression Rating Scale), sensitivity was 78.1%, and specificity was 74.6%.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12297607", "endSection": "sections.0" }, { "offsetInBeginSection": 329, "offsetInEndSection": 593, "text": "The hypothesis was supported: in contrast to psychiatric interview (68% depressed) and self-report (Beck Depression Inventory, 50% depressed), none of the patients were described as depressed in chart notes by the rehabilitation team (excluding the psychiatrists).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1410202", "endSection": "sections.0" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1571, "text": "Although there were no marked differences in the screening abilities for PSD between the scales, differences were found in factors influencing misclassification. Assessment scales with less somatic items may be recommended for the screening of PSD, particularly at the acute phase of stroke.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23167974", "endSection": "sections.0" } ] }, { "body": "What is the mechanism of action of trichostatin A (TSA) as an antitumoral agent?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22167207", "http://www.ncbi.nlm.nih.gov/pubmed/22290509", "http://www.ncbi.nlm.nih.gov/pubmed/16865256", "http://www.ncbi.nlm.nih.gov/pubmed/19649719", "http://www.ncbi.nlm.nih.gov/pubmed/22994780", "http://www.ncbi.nlm.nih.gov/pubmed/24122231", "http://www.ncbi.nlm.nih.gov/pubmed/22564421", "http://www.ncbi.nlm.nih.gov/pubmed/23451817", "http://www.ncbi.nlm.nih.gov/pubmed/12769777", "http://www.ncbi.nlm.nih.gov/pubmed/15499627", "http://www.ncbi.nlm.nih.gov/pubmed/22552321", "http://www.ncbi.nlm.nih.gov/pubmed/22476901", "http://www.ncbi.nlm.nih.gov/pubmed/12433798", "http://www.ncbi.nlm.nih.gov/pubmed/23868005", "http://www.ncbi.nlm.nih.gov/pubmed/23225425", "http://www.ncbi.nlm.nih.gov/pubmed/19887557", "http://www.ncbi.nlm.nih.gov/pubmed/17121923", "http://www.ncbi.nlm.nih.gov/pubmed/18056955", "http://www.ncbi.nlm.nih.gov/pubmed/18388912", "http://www.ncbi.nlm.nih.gov/pubmed/17218485", "http://www.ncbi.nlm.nih.gov/pubmed/16094635" ], "ideal_answer": [ "Trichostatin A (TSA) exerts antitumoral activity as a histone deacetylase inhibitor" ], "concepts": [ "http://www.biosemantics.org/jochem#4276621", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035983", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035984" ], "type": "summary", "id": "5318798bb166e2b806000014", "snippets": [ { "offsetInBeginSection": 265, "offsetInEndSection": 378, "text": "histone deacetylase inhibitor trichostatin A (TSA), an agent that also targets cancer cells and tumor vasculature", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18388912", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 82, "text": "Histone deacetylase (HDAC) inhibitors are promising antitumoral drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23225425", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 666, "text": " trichostatin A and FK901228 showed higher potency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23225425", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 154, "text": "istone deacetylase inhibitors (HDACi) show promise as a novel class of antitumoral agents and have shown the ability to induce apoptosis of tumor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887557", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 401, "text": "we conducted a functional gene screen approach named suppression of mortality by antisense rescue technique to identify the key genes responsible for the tumor-selective killing trichostatin A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887557", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 218, "text": "ydroxamic acid (HA)-based histone deacetylase (HDAC) inhibitors, with trichostatin A (TSA) as the reference compound, are potential antitumoral drugs and show promise in the creation of long-term primary cell cultures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17218485", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 137, "text": "Trichostatin A (TSA), a histone deacetylase inhibitor with promising antifibrotic and antitumoral properties", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12433798", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 356, "text": "Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24122231", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 401, "text": "Histone deacetylase inhibitors (HDACi) are anticancer agents targeting epigenetic regulation of gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868005", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 546, "text": "ive MM cell lines were treated with trichostatin A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868005", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 297, "text": "novel potential anticancer drug histone deacetylase (HDAC) and inhibitor trichostatin A (TSA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23451817", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 250, "text": "Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994780", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 131, "text": "Trichostatin A (TSA) is a potent histone deacetylase inhibitor and widely used as a promising anticancer agent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22564421", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 581, "text": "we found that a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), inhibited cell proliferation and invasion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22552321", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 402, "text": "e reported a novel potential anticancer strategy by using histone deacetylase (HDAC) inhibitor to enhance the action of endocrine therapy in ER\u03b1-positive breast cancer cell. The well-described HDAC inhibitor, trichostatin A (TSA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22476901", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 562, "text": "We determined whether the HDAC inhibitor, Tricostatin A (TSA) in combination with curcumin would produce greater antiproliferative ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22290509", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 117, "text": "trichostatin A (TSA) exert antitumor activity as histone deacetylase inhibitors, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167207", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1061, "text": "anticancer activity of anticancer agent trichostatin A (the histone deacetylase inhibitor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19649719", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 368, "text": "One of the advantages of the use of histone deacetylase inhibitors, such as TSA, is that its effects have been found to be more potent toward cancer cells compared to normal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056955", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 549, "text": " the HDAC inhibitor trichostatin A (TSA). However, only combined treatment with TSA/paclitaxel caused synergistic inhibition of cell growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17121923", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 343, "text": "a histone deacetylase inhibitor, trichostatin A (TSA), was proven to be a chemo-sensitizer on human erythroleukemia cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16865256", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 420, "text": "we demonstrated that the HDIs butyrate and trichostatin A (TSA) directly repress c-Src proto-oncogene expression in many cancer cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16094635", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 126, "text": "istone deacetylase inhibitors (HDIs) induce cell cycle arrest, differentiation and/or apoptosis in numerous cancer cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16094635", "endSection": "abstract" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1427, "text": "The results suggest that TSA inhibits bladder carcinoma cell growth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15499627", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 249, "text": "istone deacetylase inhibitors (HDACis) are emerging as a promising new class of anticancer agents displaying growth-inhibitory activity and low toxicity in vivo. In this study, we examined the effect of sodium butyrate (NaB) and trichostatin A (TSA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15499627", "endSection": "abstract" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1687, "text": "the in vitro effects of HDAC inhibitors, such as trichostatin A (TSA), sodium butyrate, depsipeptide (FR901228, FK228), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), and the demethylating agent, 5-aza-CdR used alone and in combination treatment of human cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12769777", "endSection": "abstract" } ] }, { "body": "Is there an association between serum interleukin-6 concentrations and outcomes of stroke patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17337911", "http://www.ncbi.nlm.nih.gov/pubmed/19901973", "http://www.ncbi.nlm.nih.gov/pubmed/18048088", "http://www.ncbi.nlm.nih.gov/pubmed/14730251", "http://www.ncbi.nlm.nih.gov/pubmed/18685925", "http://www.ncbi.nlm.nih.gov/pubmed/25295149" ], "ideal_answer": [ "Yes. Greater serum interleukin-6 concentrations are associated with worse outcomes in ischemic and hemmorhagic stroke patients" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/IL6_PIG" ], "type": "yesno", "id": "54cf4bc3f693c3b16b00000d", "snippets": [ { "offsetInBeginSection": 1418, "offsetInEndSection": 1496, "text": " In addition, IL-6 concentrations affect clinical outcomes in ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25295149", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1363, "text": "After appropriate adjustment, the odds ratios for the association of markers and poor outcome (comparing the upper and the lower third) were interleukin-6, 3.1 (95% CI: 1.9-5.0); C-reactive protein, 1.9 (95% CI: 1.2-3.1); fibrinogen, 1.5 (95% CI: 1.0-2.36); white cell count, 2.1 (95% CI: 1.3-3.4); and glucose 1.3 (95% CI: 0.8-2.1). The results for interleukin-6 were similar to other studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901973", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1992, "text": "-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18685925", "endSection": "abstract" }, { "offsetInBeginSection": 2116, "offsetInEndSection": 2216, "text": "In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18685925", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1551, "text": "Initially elevated levels of hs-IL-6 at presentation further correlated with unfavorable clinical outcomes (by NIHSS and mRs) at both time points. Analysis of variance in the different quartiles identified an hs-IL-6 gradient-dependent correlation at both time points, such that the higher the initial hs-IL-6 concentration, the higher the elevation in inflammatory biomarkers and the poorer the neurological state at both time points (p<0.001 for NIHSS and p=0.001 for mRs, for trend across quartiles). CONCLUSIONS: This study demonstrates the potential of employing hs-IL-6 as an early stage biomarker for the prognosis of acute ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18048088", "endSection": "abstract" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1325, "text": "Another negative correlation was found between IL-6 and CNS scores (r = -0.451, p = 0.000).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17337911", "endSection": "abstract" }, { "offsetInBeginSection": 1816, "offsetInEndSection": 1950, "text": "In addition, increased levels of IL-6 and reduced levels of protein C and protein S may play a role in acute ischemic stroke severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17337911", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 490, "text": "Variables that are predictors of adverse stroke outcome include erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14730251", "endSection": "abstract" } ] }, { "body": "Could bioprinting be used in regenerative medicine against bone disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21798570", "http://www.ncbi.nlm.nih.gov/pubmed/25866560", "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "http://www.ncbi.nlm.nih.gov/pubmed/25376489" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "D004194" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0049941", "o": "D001847" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0032080", "o": "D001842" } ], "ideal_answer": [ "The developments in bioprinting (3D cell printing) techniques will be used in regenerative medicine and may allow the fabrication of customized implants for patients suffering in bone diseases in the future, once several technological limitations are addressed." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008511", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001847", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062028", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044968", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.disease-ontology.org/api/metadata/DOID:0080001" ], "type": "yesno", "id": "5713968e1174fb175500000d", "snippets": [ { "offsetInBeginSection": 561, "offsetInEndSection": 866, "text": "Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25866560", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 1463, "text": "It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376489", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1933, "text": "These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376489", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1100, "text": "3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1464, "text": "a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376489", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1464, "text": "These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376489", "endSection": "abstract" } ] }, { "body": "Idarucizumab is an antidote of which drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26069913", "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "http://www.ncbi.nlm.nih.gov/pubmed/26088576", "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "http://www.ncbi.nlm.nih.gov/pubmed/26088268" ], "ideal_answer": [ "Idarucizumab is an antidote of Dabigatran. It is used for Dabigatran Reversal." ], "exact_answer": [ "dabigatran" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000931" ], "type": "factoid", "id": "56c079b1ef6e394741000022", "snippets": [ { "offsetInBeginSection": 197, "offsetInEndSection": 355, "text": "With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26069913", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 966, "text": "Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Idarucizumab Improves Outcome in Murine Brain Hemorrhage Related to Dabigatran.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "title" }, { "offsetInBeginSection": 145, "offsetInEndSection": 401, "text": "We examined the efficacy of idarucizumab, an antibody fragment binding to dabigatran, in a mouse model of OAC-ICH. Dabigatran etexilate (DE) dose-dependently prolonged diluted thrombin time and tail-vein bleeding time, which were reversed by idarucizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 779, "text": "Thus, idarucizumab prevents excess intracerebral hematoma formation in mice anticoagulated with dabigatran and reduces mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "BACKGROUND: Idarucizumab is a monoclonal antibody fragment that binds dabigatran with high affinity in a 1:1 molar ratio. We investigated the safety, tolerability, and efficacy of increasing doses of idarucizumab for the reversal of anticoagulant effects of dabigatran in a two-part phase 1 study (rising-dose assessment and dose-finding, proof-of-concept investigation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "endSection": "title" }, { "offsetInBeginSection": 3048, "offsetInEndSection": 3337, "text": "INTERPRETATION: These phase 1 results show that idarucizumab was associated with immediate, complete, and sustained reversal of dabigatran-induced anticoagulation in healthy men, and was well tolerated with no unexpected or clinically relevant safety concerns, supporting further testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 37, "text": "Idarucizumab for Dabigatran Reversal.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "title" }, { "offsetInBeginSection": 99, "offsetInEndSection": 468, "text": "Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran.METHODS: We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "abstract" }, { "offsetInBeginSection": 1835, "offsetInEndSection": 1936, "text": ".CONCLUSIONS: Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 260, "text": "We examined the efficacy of idarucizumab, an antibody fragment binding to dabigatran, in a mouse model of OAC-ICH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "abstract" } ] }, { "body": "What are the main clinical characteristics of Pendred syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15355436", "http://www.ncbi.nlm.nih.gov/pubmed/15611902", "http://www.ncbi.nlm.nih.gov/pubmed/23965030", "http://www.ncbi.nlm.nih.gov/pubmed/17876604", "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "http://www.ncbi.nlm.nih.gov/pubmed/21511235", "http://www.ncbi.nlm.nih.gov/pubmed/8630497", "http://www.ncbi.nlm.nih.gov/pubmed/19205523", "http://www.ncbi.nlm.nih.gov/pubmed/9302427", "http://www.ncbi.nlm.nih.gov/pubmed/11919333", "http://www.ncbi.nlm.nih.gov/pubmed/8706311", "http://www.ncbi.nlm.nih.gov/pubmed/17322586", "http://www.ncbi.nlm.nih.gov/pubmed/9604973", "http://www.ncbi.nlm.nih.gov/pubmed/9849679", "http://www.ncbi.nlm.nih.gov/pubmed/17766716", "http://www.ncbi.nlm.nih.gov/pubmed/19235486", "http://www.ncbi.nlm.nih.gov/pubmed/18250610", "http://www.ncbi.nlm.nih.gov/pubmed/21745434", "http://www.ncbi.nlm.nih.gov/pubmed/10902795", "http://www.ncbi.nlm.nih.gov/pubmed/22906308" ], "ideal_answer": [ "Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification." ], "exact_answer": [ [ "congenital sensorineural deafness" ], [ "goiter" ], [ "impaired iodide organification" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034381", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003638" ], "type": "list", "id": "56d8b47a51531f7e33000004", "snippets": [ { "offsetInBeginSection": 63, "offsetInEndSection": 264, "text": "Obligatory features are profound deafness in childhood and defective organic binding of iodine in the thyroid gland. Therefore, goiter is a common symptom. Hypoplasia of the cochlea is another feature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9604973", "endSection": "abstract" }, { "offsetInBeginSection": 1262, "offsetInEndSection": 1408, "text": "If a child has progressive sensorineural deafness and a widened vestibular aqueduct, it is important to consider a diagnosis of Pendred syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9604973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Inherited as an autosomal recessive trait, Pendred syndrome is a disease that shows congenital sensorineural hearing loss and goiter, with a positive finding in the perchlorate discharge test. Pendred syndrome results from various mutations in the PDS/SLC26A4 gene that cause production of an abnormal pendrin protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17322586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the PDS gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250610", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 831, "text": "Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1385, "text": "Aside from the branchio-otorenal syndrome, Pendred syndrome is the only other known genetic disorder with a widened vestibular aqueduct.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9604973", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1022, "text": "The clinical diagnosis of Pendred syndrome was based on the laboratory and sonographic signs of thyroid dyshormonogenesis in association with sensorineural hearing loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17876604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1395, "text": "Progressive sensorineural hearing loss and widened vestibular aqueducts are characteristic features of Pendred's syndrome, which provides the opportunity to diagnose Pendred's syndrome clinically in the first few years of life, as has recently been suggested in a case report (Cremers et al., Progressive sensorineural hearing loss and a widend vestibular aqueduct in Pendred syndrome, Arch.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9849679", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 843, "text": "Pendred syndrome is the most common syndromal form of deafness, yet the primary defect remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8630497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Pendred syndrome is one of the most common hereditary determined diseases in patients with syndromic sensorineural hearing impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906308", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1243, "text": "The clinical diagnosis of Pendred syndrome was based on the laboratory and ultrasonographic signs of thyroid dyshormonogenesis (elevated TSH, low T4/fT4, goitre or normal thyroid volume) in association with sensorineural hearing loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19235486", "endSection": "abstract" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1242, "text": "The clinical diagnosis of Pendred syndrome was based on the laboratory and ultrasonographic signs of thyroid dyshormonogenesis (elevated TSH, low T4/fT4, goitre or normal thyroid volume) in association with sensorineural hearing loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19235486", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1313, "text": "Individuals were assigned affected status based on the characteristic clinical features of Pendred's syndrome, namely the presence of congenital sensorineural hearing loss and the appearance in early life of a goitre. Additionally, at least one affected member from each sibship had a characteristic positive perchlorate discharge test (Morgans & Trotter, 1958).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8706311", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1313, "text": "Individuals were assigned affected status based on the characteristic clinical features of Pendred's syndrome, namely the presence of congenital sensorineural hearing loss and the appearance in early life of a goitre. Additionally, at least one affected member from each sibship had a characteristic positive perchlorate discharge test (Morgans & Trotter, 1958).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8706311", "endSection": "abstract" } ] }, { "body": "What is the Pfam database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19614588", "http://www.ncbi.nlm.nih.gov/pubmed/18957444", "http://www.ncbi.nlm.nih.gov/pubmed/23603847", "http://www.ncbi.nlm.nih.gov/pubmed/20537955", "http://www.ncbi.nlm.nih.gov/pubmed/20944204", "http://www.ncbi.nlm.nih.gov/pubmed/24297255" ], "ideal_answer": [ "The Pfam database provides a collection of curated protein families." ], "exact_answer": [ "The Pfam database is a collection of curated protein families." ], "type": "factoid", "id": "5709f027cf1c32585100001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20537955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Protein domains are the common currency of protein structure and function. Over 10,000 such protein families have now been collected in the Pfam database. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19614588", "endSection": "abstract" } ] }, { "body": "What is a popular mesaure of gene expression in RNA-seq experiments?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19835606", "http://www.ncbi.nlm.nih.gov/pubmed/21385047", "http://www.ncbi.nlm.nih.gov/pubmed/22971240", "http://www.ncbi.nlm.nih.gov/pubmed/23222129", "http://www.ncbi.nlm.nih.gov/pubmed/23428641", "http://www.ncbi.nlm.nih.gov/pubmed/22232676", "http://www.ncbi.nlm.nih.gov/pubmed/22287631", "http://www.ncbi.nlm.nih.gov/pubmed/21994224", "http://www.ncbi.nlm.nih.gov/pubmed/22872506", "http://www.ncbi.nlm.nih.gov/pubmed/22688717", "http://www.ncbi.nlm.nih.gov/pubmed/21179022" ], "ideal_answer": [ "A commonly used measure for gene expression in RNA-seq experiments is Reads Per Kilobase per Million mapped reads (RPKM). In ocasions, and to account for partially mapped read, read Fragments per Kilobase per Million mapped reads (FPKM) is alternatively used." ], "exact_answer": [ "Reads Per Kilobase per Million mapped reads (RPKM)" ], "type": "factoid", "id": "5178d6be8ed59a060a000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "Measures of RNA abundance are important for many areas of biology and often obtained from high-throughput RNA sequencing methods such as Illumina sequence data. These measures need to be normalized to remove technical biases inherent in the sequencing approach, most notably the length of the RNA species and the sequencing depth of a sample. These biases are corrected in the widely used reads per kilobase per million reads (RPKM) measure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872506", "endSection": "sections.0" } ] }, { "body": "Is macroautophagy a selective degradation process?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18362514", "http://www.ncbi.nlm.nih.gov/pubmed/21681022", "http://www.ncbi.nlm.nih.gov/pubmed/23064313", "http://www.ncbi.nlm.nih.gov/pubmed/21787863", "http://www.ncbi.nlm.nih.gov/pubmed/19619495", "http://www.ncbi.nlm.nih.gov/pubmed/19717456", "http://www.ncbi.nlm.nih.gov/pubmed/19793921", "http://www.ncbi.nlm.nih.gov/pubmed/20498061", "http://www.ncbi.nlm.nih.gov/pubmed/23267366", "http://www.ncbi.nlm.nih.gov/pubmed/20346769", "http://www.ncbi.nlm.nih.gov/pubmed/11739783", "http://www.ncbi.nlm.nih.gov/pubmed/21818581", "http://www.ncbi.nlm.nih.gov/pubmed/23159909", "http://www.ncbi.nlm.nih.gov/pubmed/20659474", "http://www.ncbi.nlm.nih.gov/pubmed/22017874", "http://www.ncbi.nlm.nih.gov/pubmed/20543572", "http://www.ncbi.nlm.nih.gov/pubmed/22561104", "http://www.ncbi.nlm.nih.gov/pubmed/17351330", "http://www.ncbi.nlm.nih.gov/pubmed/16874038", "http://www.ncbi.nlm.nih.gov/pubmed/20359542", "http://www.ncbi.nlm.nih.gov/pubmed/17622797", "http://www.ncbi.nlm.nih.gov/pubmed/20417604", "http://www.ncbi.nlm.nih.gov/pubmed/21576396", "http://www.ncbi.nlm.nih.gov/pubmed/19242639", "http://www.ncbi.nlm.nih.gov/pubmed/20364111", "http://www.ncbi.nlm.nih.gov/pubmed/22554685", "http://www.ncbi.nlm.nih.gov/pubmed/20798600", "http://www.ncbi.nlm.nih.gov/pubmed/22518139", "http://www.ncbi.nlm.nih.gov/pubmed/20703094", "http://www.ncbi.nlm.nih.gov/pubmed/16203860", "http://www.ncbi.nlm.nih.gov/pubmed/17204848", "http://www.ncbi.nlm.nih.gov/pubmed/12960228", "http://www.ncbi.nlm.nih.gov/pubmed/18539900", "http://www.ncbi.nlm.nih.gov/pubmed/23295856", "http://www.ncbi.nlm.nih.gov/pubmed/22915758", "http://www.ncbi.nlm.nih.gov/pubmed/22977244", "http://www.ncbi.nlm.nih.gov/pubmed/21839922", "http://www.ncbi.nlm.nih.gov/pubmed/23046644", "http://www.ncbi.nlm.nih.gov/pubmed/18336289", "http://www.ncbi.nlm.nih.gov/pubmed/21383079", "http://www.ncbi.nlm.nih.gov/pubmed/22481944", "http://www.ncbi.nlm.nih.gov/pubmed/21913110", "http://www.ncbi.nlm.nih.gov/pubmed/22717525", "http://www.ncbi.nlm.nih.gov/pubmed/21343297", "http://www.ncbi.nlm.nih.gov/pubmed/22935563", "http://www.ncbi.nlm.nih.gov/pubmed/9184851", "http://www.ncbi.nlm.nih.gov/pubmed/11309418", "http://www.ncbi.nlm.nih.gov/pubmed/9296392", "http://www.ncbi.nlm.nih.gov/pubmed/21431350" ], "triples": [ { "p": "http://linkedlifedata.com/resource/geneontology/namespace", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236", "o": "biological_process" }, { "p": "http://linkedlifedata.com/resource/geneontology/regulates", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0016241", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q12092", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/P25694", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q5RBA5", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q03818", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q07528", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q55CC5", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q501R9", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q9VHH2", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016236" }, { "p": "http://www.w3.org/2000/01/rdf-schema#comment", "s": "http://purl.uniprot.org/go/0016236", "o": "The major inducible pathway for the general turnover of cytoplasmic constituents in eukaryotic cells, it is also responsible for the degradation of active cytoplasmic enzymes and organelles during nutrient starvation. Macroautophagy involves the formation of double-membrane-bounded autophagosomes which enclose the cytoplasmic constituent targeted for degradation in a membrane-bounded structure, which then fuse with the lysosome (or vacuole) releasing a single-membrane-bounded autophagic bodies which are then degraded within the lysosome (or vacuole). Though once thought to be a purely non-selective process, it appears that some types of macroautophagy, e.g. macropexophagy, macromitophagy, may involve selective targeting of the targets to be degraded." } ], "ideal_answer": [ "Yes. Macroautophagy (commonly referred to simply as autophagy) is a catabolic process conserved throughout the eukaryotes, and is distinct from other forms of autophagy by the formation of the autophagosome: this is a vesicle-like formation surrounded by a double membrane that sequesters the cytoplasmic material to be degraded. It was initially considered that macroautophagy was a bulk process; however, recent findings illustrate that specific cargos (ranging from misfolded or excess proteins, to organelles or even bacterial cells) can be selectively targeted to the pre-autophagosome membrane (i.e. the phagophore) and finally to the vacuoles/lysosomes for their degradation." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0035459", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016241", "http://www.uniprot.org/uniprot/ATG1_PICPA", "http://www.uniprot.org/uniprot/ATG11_PICPA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016236", "http://www.uniprot.org/uniprot/ATG7_PICPA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0009056" ], "type": "yesno", "id": "51bedaac3148fdcc22da7188", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 19, "text": "Selective autophagy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839922", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Macroautophagy (autophagy) is a bulk degradation system for cytoplasmic components and is ubiquitously found in eukaryotic cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839922", "endSection": "sections.0" }, { "offsetInBeginSection": 505, "offsetInEndSection": 574, "text": "Here we show that selective autophagy downregulates Ty1 transposition", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839922", "endSection": "sections.0" }, { "offsetInBeginSection": 723, "offsetInEndSection": 908, "text": "We propose that selective autophagy safeguards genome integrity against excessive insertional mutagenesis caused during nutrient starvation by transposable elements in eukaryotic cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839922", "endSection": "sections.0" }, { "offsetInBeginSection": 438, "offsetInEndSection": 577, "text": "Moreover, it is becoming apparent that proteins, organelles, and pathogens can be targeted for autophagic clearance by selective mechanisms", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20498061", "endSection": "sections.0" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1154, "text": "Cell spreading required ref(2)P, the Drosophila p62 multiadaptor, implicating selective autophagy as a novel mechanism for modulating cortical dynamics", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20498061", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "The selective macroautophagic degradation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417604", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "There is growing evidence that macroautophagic cargo is not limited to bulk cytosol in response to starvation and can occur selectively for substrates, including aggregated proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417604", "endSection": "sections.0" }, { "offsetInBeginSection": 183, "offsetInEndSection": 468, "text": "It remains unclear, however, whether starvation-induced and selective macroautophagy share identical adaptor molecules to capture their cargo. Here, we report that Alfy, a phosphatidylinositol 3-phosphate-binding protein, is central to the selective elimination of aggregated proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417604", "endSection": "sections.0" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1071, "text": "We propose that Alfy plays a key role in selective macroautophagy by bridging cargo to the molecular machinery that builds autophagosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417604", "endSection": "sections.0" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1032, "text": "Thus, cytoplasmic NBR1 might be important to maintain basal levels of selective macroautophagy in these neurons.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23295856", "endSection": "sections.0" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1181, "text": "we could show that Smatg8 and Smatg4 are not only required for nonselective macroautophagy, but for selective macropexophagy as well.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064313", "endSection": "sections.0" }, { "offsetInBeginSection": 186, "offsetInEndSection": 311, "text": "The latter is performed by proteasome-mediated degradation, chaperone-mediated autophagy (CMA), and selective macroautophagy,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046644", "endSection": "sections.0" }, { "offsetInBeginSection": 429, "offsetInEndSection": 558, "text": "Here we demonstrate a role for PtdIns 4-kinases and PtdIns4P 5-kinases in selective and nonselective types of autophagy in yeast.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22977244", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Macroautophagy (hereafter autophagy) is a degradative cellular pathway that protects eukaryotic cells from stress, starvation, and microbial infection.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22977244", "endSection": "sections.0" }, { "offsetInBeginSection": 150, "offsetInEndSection": 351, "text": "Previously, we showed that macroautophagy is necessary for conidiation in the rice-blast fungus Magnaporthe oryzae. Here, we analyzed the physiological function(s) of selective autophagy in Magnaporthe", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561104", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22017874", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Selective macroautophagy (autophagy) of ubiquitinated protein is implicated as a compensatory mechanism of the ubiquitin-proteasome system. p62/SQSTM1 is a key molecule managing autophagic clearance of polyubiquitinated proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22017874", "endSection": "sections.0" }, { "offsetInBeginSection": 180, "offsetInEndSection": 623, "text": "Whole organelle turnover is mediated through macroautophagy, a process by which autophagosomes deliver mitochondria to the lysosome for hydrolytic degradation. While mitochondrial autophagy can occur as part of a nonselective upregulation of autophagy, selective degradation of damaged or unneeded mitochondria (mitophagy) is a rapidly growing area in development, cancer, and neurodegeneration, particularly with regard to Parkinson's disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913110", "endSection": "sections.0" }, { "offsetInBeginSection": 192, "offsetInEndSection": 405, "text": "BAG3 was recently described as a mediator of a novel macroautophagy pathway that uses the specificity of heat shock protein 70 (HSP70) to misfolded proteins and also involves other protein partners, such as HSPB8.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21681022", "endSection": "sections.0" }, { "offsetInBeginSection": 94, "offsetInEndSection": 254, "text": "two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20798600", "endSection": "sections.0" }, { "offsetInBeginSection": 448, "offsetInEndSection": 520, "text": "Here we show that whole mitochondria are turned over via macroautophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20798600", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Does Huntingtin play a role in selective macroautophagy?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20703094", "endSection": "title" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1002, "text": "In the discussion here I suggest that Htt may have a normal function in the lysosomal mechanism of selective macroautophagy involved in its own degradation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20703094", "endSection": "sections.0" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1199, "text": "Macroautophagy induced by ethanol seemed to be selective for damaged mitochondria and accumulated lipid droplets, but not long-lived proteins, which could account for its protective effects", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20659474", "endSection": "sections.0" }, { "offsetInBeginSection": 341, "offsetInEndSection": 520, "text": "Although macroautophagy can be nonspecific, there are many examples of selective sequestration including pexophagy, mitophagy and the cytoplasm to vacuole targeting (Cvt) pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20543572", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Mitochondria autophagy (mitophagy) is the process of selective degradation of mitochondria that has an important role in mitochondrial quality control.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20364111", "endSection": "sections.0" }, { "offsetInBeginSection": 367, "offsetInEndSection": 497, "text": "One of the genes identified, YLR356W, is required for mitophagy, but not for macroautophagy or other types of selective autophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20364111", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "A genomic screen for yeast mutants defective in selective mitochondria autophagy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793921", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Mitophagy is the process of selective mitochondrial degradation via autophagy, which has an important role in mitochondrial quality control.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793921", "endSection": "sections.0" }, { "offsetInBeginSection": 363, "offsetInEndSection": 801, "text": "Analysis of this set of targeted deletion mutants demonstrated that loss of any of the 16 genes necessary for nonselective macroautophagy renders the fungus unable to cause rice blast disease, due to impairment of both conidial programmed cell death and appressorium maturation. In contrast, genes necessary only for selective forms of autophagy, such as pexophagy and mitophagy, are dispensable for appressorium-mediated plant infection.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19717456", "endSection": "sections.0" }, { "offsetInBeginSection": 480, "offsetInEndSection": 579, "text": "This gene is not required for other types of selective autophagy or for nonspecific macroautophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19619495", "endSection": "sections.0" }, { "offsetInBeginSection": 663, "offsetInEndSection": 1107, "text": "However, in contrast to the core autophagy genes such as atg5 and atg7, expression of ulk1 is not essential for induction of macroautophagy in response to nutrient deprivation or for survival of newborn mice. Together, these data suggest that the ATG1 homologue, Ulk1, is a component of the selective autophagy machinery that leads to the elimination of organelles in erythroid cells rather that an essential mechanistic component of autophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539900", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 530, "text": "Growing evidence supports an active role for dysregulated macroautophagy (autophagic stress) in neuronal cell death and neurodegeneration. Alterations in mitochondrial function and dynamics are also strongly implicated in neurodegenerative diseases. Interestingly, whereas the core autophagy machinery is evolutionarily conserved and shared among constitutive and induced or selective autophagy, recent studies implicate distinct mechanisms regulating mitochondrial autophagy (mitophagy) in response to general autophagic stimuli.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17622797", "endSection": "sections.0" }, { "offsetInBeginSection": 381, "offsetInEndSection": 814, "text": "We discovered that activation of the UPR in yeast also induces a new branch of macroautophagy that selectively targets the ER. We term this process \"ER-phagy\", in analogy to pexophagy and mitophagy, the two other known forms of organelle-specific marcoautophagy. ER-phagy involves the generation of autophagosomes that selectively include ER membranes and whose delimiting double membranes also derive, at least in part, from the ER.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17351330", "endSection": "sections.0" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1412, "text": "This suggests that in fungi an organism-specific form of selective autophagy may occur, for which specialized Atg proteins have evolved.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17204848", "endSection": "sections.0" }, { "offsetInBeginSection": 112, "offsetInEndSection": 251, "text": "ransfer of Y. lipolytica cells from oleate/ethylamine to glucose/ammonium chloride medium leads to selective macroautophagy of peroxisomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16874038", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Insulin-dependent signaling regulates azurophil granule-selective macroautophagy in human myeloblastic cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12960228", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "We show that insulin-dependent signals regulate azurophil granule-selective macroautophagy in human myeloid cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12960228", "endSection": "sections.0" }, { "offsetInBeginSection": 579, "offsetInEndSection": 773, "text": "By contrast, other organelles, including the mitochondria, endoplasmic reticulum, and Golgi apparatus remained intact, indicating that the macroautophagy selectively targeted azurophil granules.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12960228", "endSection": "sections.0" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1589, "text": "Thus, insulin-dependent signals are responsible for the control of azurophil granule-selective macroautophagy via Akt-dependent pathways", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12960228", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Eukaryotic cells have the ability to degrade proteins and organelles by selective and nonselective modes of micro- and macroautophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11739783", "endSection": "sections.0" }, { "offsetInBeginSection": 212, "offsetInEndSection": 316, "text": "For example, pexophagy is a selective process for the regulated degradation of peroxisomes by autophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11739783", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "We have characterized biochemically, morphologically, and genetically two distinct pathways for the selective degradation of peroxisomes in Pichia pastoris. These pathways are independently regulated and analogous to microautophagy and macroautophagy that have been defined in mammalian cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9296392", "endSection": "sections.0" }, { "offsetInBeginSection": 1366, "offsetInEndSection": 1611, "text": "If we are willing to slightly modify our definition of autophagy, with a focus on \"degradation of a cell's own components through the lysosomal/vacuolar machinery,\" we can include a newly documented process, programmed nuclear destruction (PND).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159909", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Autophagy is a lysosomal degradation pathway that can sequester cytosolic material, including organelles, nonspecifically in a process called nonselective macroautophagy, or target specific protein aggregates designated for destruction in a process called selective autophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22915758", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Selective macroautophagy uses double-membrane vesicles, termed autophagosomes, to transport cytoplasmic pathogens, organelles and protein complexes to the vacuole for degradation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22717525", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Autophagy (macroautophagy), a highly conserved eukaryotic mechanism, is a non-selective degradation process, helping to maintain a balance between the synthesis, degradation and subsequent recycling of macromolecules to overcome various stress conditions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22554685", "endSection": "sections.0" }, { "offsetInBeginSection": 180, "offsetInEndSection": 339, "text": "Whole organelle turnover is mediated through macroautophagy, a process by which autophagosomes deliver mitochondria to the lysosome for hydrolytic degradation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913110", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Macroautophagy is a catabolic process by which the cell degrades cytoplasmic components through the lysosomal machinery.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21818581", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Macroautophagy maintains cellular homeostasis through targeting cytoplasmic contents and organelles into autophagosomes for degradation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21787863", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Macroautophagy is a catabolic process by which cytosolic components are sequestered by double membrane vesicles called autophagosomes and sorted to the lysosomes/vacuoles to be degraded.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21343297", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Macroautophagy (hereafter autophagy) is a cellular degradation process, which in yeast is induced in response to nutrient deprivation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20359542", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Macroautophagy was thought to be an unspecific bulk degradation process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20346769", "endSection": "sections.0" }, { "offsetInBeginSection": 456, "offsetInEndSection": 770, "text": "Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles, and can be monitored by imaging the incorporation of microtubule-associated light chain 3 (LC3) fused to a fluorescent protein (GFP or mCherry) into nascent autophagosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19242639", "endSection": "sections.0" }, { "offsetInBeginSection": 122, "offsetInEndSection": 301, "text": "Beside macroautophagy, there are several forms of selective autophagy, including chaperone-mediated autophagy (CMA), cytoplasm to vacuole targeting (Cvt), pexophagy and mitophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18362514", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Macroautophagy (commonly referred to as autophagy) is the process by which intact organelles and/or large portions of the cytoplasm are engulfed within double-membraned autophagic vacuoles for degradation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18336289", "endSection": "sections.0" }, { "offsetInBeginSection": 471, "offsetInEndSection": 663, "text": "This analysis demonstrated that Atg proteins required for non-selective macroautophagy are conserved from yeast to man, stressing the importance of this process in cell survival and viability.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17204848", "endSection": "sections.0" }, { "offsetInBeginSection": 90, "offsetInEndSection": 198, "text": "Part of the degradation of intracellular proteins occurs in the lysosomes and is mediated by macroautophagy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9184851", "endSection": "sections.0" } ] }, { "body": "Inhibition of which enzyme is mechanism of action of alisertib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24043741", "http://www.ncbi.nlm.nih.gov/pubmed/22488249", "http://www.ncbi.nlm.nih.gov/pubmed/22940834", "http://www.ncbi.nlm.nih.gov/pubmed/23037716", "http://www.ncbi.nlm.nih.gov/pubmed/23431463", "http://www.ncbi.nlm.nih.gov/pubmed/22753585", "http://www.ncbi.nlm.nih.gov/pubmed/22772063", "http://www.ncbi.nlm.nih.gov/pubmed/23153524", "http://www.ncbi.nlm.nih.gov/pubmed/23755375", "http://www.ncbi.nlm.nih.gov/pubmed/23180582", "http://www.ncbi.nlm.nih.gov/pubmed/24501545", "http://www.ncbi.nlm.nih.gov/pubmed/22863010", "http://www.ncbi.nlm.nih.gov/pubmed/24101146", "http://www.ncbi.nlm.nih.gov/pubmed/22767670", "http://www.ncbi.nlm.nih.gov/pubmed/23755370", "http://www.ncbi.nlm.nih.gov/pubmed/22016509", "http://www.ncbi.nlm.nih.gov/pubmed/23847761", "http://www.ncbi.nlm.nih.gov/pubmed/23446853", "http://www.ncbi.nlm.nih.gov/pubmed/22350019", "http://www.ncbi.nlm.nih.gov/pubmed/23723712", "http://www.ncbi.nlm.nih.gov/pubmed/24240108", "http://www.ncbi.nlm.nih.gov/pubmed/22972611" ], "ideal_answer": [ "Alisertib (MLN8237) is selective Aurora kinase inhibitor that acts by interfering with spindle organization and chromosome alignment during mitosis. It has been tested in patients with gastric cancer, breast cancer, relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas, epithelial ovarian, fallopian tube, and primary peritoneal carcinoma." ], "exact_answer": [ "aurora kinase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ], "type": "factoid", "id": "531dd4af267d7dd05300000d", "snippets": [ { "offsetInBeginSection": 1197, "offsetInEndSection": 1363, "text": "Inhibition of AURKA using an investigational small-molecule specific inhibitor, alisertib, decreased the HDM2 protein level and induced P53 transcriptional activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Preclinical pharmacokinetic/pharmacodynamic/efficacy relationships for alisertib, an investigational small-molecule inhibitor of Aurora A kinase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101146", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 86, "text": "Alisertib (MLN8237) is an investigational inhibitor of Aurora A kinase (AAK).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101146", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 680, "text": "The spindle organization defects induced by alisertib have been used to develop a pharmacodynamic (PD) assay for Aurora A inhibition based on the percentage of mitotic cells with proper chromosomal alignment at the metaphase plate (% aligned spindles, abbreviated as AS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24101146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24043741", "endSection": "title" }, { "offsetInBeginSection": 144, "offsetInEndSection": 298, "text": "We therefore designed a phase II study of alisertib, a selective AAK inhibitor, in patients with relapsed and refractory aggressive non-Hodgkin lymphomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24043741", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1204, "text": "In addition, we employed vMCF-7DRaf-1 cells that display high levels of endogenous cyclin-A and demonstrated that molecular targeting of Aurora-A by Alisertib reduces cyclin-A expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153524", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 278, "text": "Alisertib (MLN8237) an investigational agent that inhibits Aurora A Ser/Thr kinase has shown activity in PTCL patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153524", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 951, "text": "We further find that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22772063", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 390, "text": "This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or -resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22772063", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 251, "text": "This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational oral drug MLN8237 (alisertib), a small-molecule Aurora A kinase (AAK) inhibitor, in 87 adult patients with advanced solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22767670", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 306, "text": "This phase I study investigated the safety, pharmacokinetics, and pharmacodynamics of MLN8237 (alisertib), an investigational, oral, selective AAK inhibitor, in 59 adults with advanced solid tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22753585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO-dependent mechanism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488249", "endSection": "title" }, { "offsetInBeginSection": 113, "offsetInEndSection": 244, "text": "The investigational drug alisertib (MLN8237) is a novel Aurora A kinase inhibitor being studied in multiple Phase I and II studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488249", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1382, "text": " Our collective data indicate that targeting Aurora A with alisertib represents a novel approach to increase the efficacy of ara-C that warrants further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016509", "endSection": "title" }, { "offsetInBeginSection": 266, "offsetInEndSection": 413, "text": "Here, we describe preclinical characterization of alisertib (MLN8237), a selective AAK inhibitor, incorporating these novel pharmacodynamic assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016509", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 587, "text": "We investigated the selectivity of alisertib for AAK and ABK and studied the antitumor and antiproliferative activity of alisertib in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016509", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1193, "text": "Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells and produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model, a phenotype consistent with AAK inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016509", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1662, "text": "Alisertib is a selective and potent inhibitor of AAK. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016509", "endSection": "abstract" } ] }, { "body": "List the three most prevalent pathogenic species of Borrelia in Europe.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22522688", "http://www.ncbi.nlm.nih.gov/pubmed/23837798", "http://www.ncbi.nlm.nih.gov/pubmed/25273355", "http://www.ncbi.nlm.nih.gov/pubmed/24533160", "http://www.ncbi.nlm.nih.gov/pubmed/24446554", "http://www.ncbi.nlm.nih.gov/pubmed/25120960", "http://www.ncbi.nlm.nih.gov/pubmed/24886071", "http://www.ncbi.nlm.nih.gov/pubmed/23838444", "http://www.ncbi.nlm.nih.gov/pubmed/22445929", "http://www.ncbi.nlm.nih.gov/pubmed/21876490", "http://www.ncbi.nlm.nih.gov/pubmed/25333277", "http://www.ncbi.nlm.nih.gov/pubmed/25409015", "http://www.ncbi.nlm.nih.gov/pubmed/23045802", "http://www.ncbi.nlm.nih.gov/pubmed/24623628", "http://www.ncbi.nlm.nih.gov/pubmed/22742788" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7570463", "o": "NCI Thesaurus" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0015176", "o": "http://linkedlifedata.com/resource/umls/label/A0056849" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0015176", "o": "http://linkedlifedata.com/resource/umls/label/A0056850" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0056848", "o": "Europe" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0015176", "o": "http://linkedlifedata.com/resource/umls/label/A7570463" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0015176", "o": "http://linkedlifedata.com/resource/umls/label/A0056848" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0015176", "o": "http://linkedlifedata.com/resource/umls/label/A0056849" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0015176", "o": "http://linkedlifedata.com/resource/umls/label/A0056847" } ], "ideal_answer": [ "The most prevalent pathogenic species of Borrelia in Europe are: B. afzelii, B. garinii and B. burgdorferi ss." ], "exact_answer": [ [ "B. afzelii" ], [ "B. garinii" ], [ "B. burgdorferi ss." ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015748", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005060", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005061", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013045", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025065", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001899", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001898", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058865" ], "type": "list", "id": "54edaee3445c3b5a5f000003", "snippets": [ { "offsetInBeginSection": 299, "offsetInEndSection": 577, "text": " The Borrelia species causing Lyme borreliosis in Europe express different OspA serotypes on their surface, B. burgdorferi (serotype 1), B. afzelii (serotype 2), B. garinii (serotypes, 3, 5 and 6) and B. bavariensis (serotype 4), while only B. burgdorferi is present in the US. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25273355", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1169, "text": "Moreover we detected Borrelia spielmanii, Borrelia miyamotoi, Babesia divergens, and Babesia venatorum for the first time in Danish ticks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25120960", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 797, "text": "We successfully determined the prevalence of expected (Borrelia burgdorferi sensu lato", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25120960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia. There is limited understanding of large scale entomological risk patterns of B. miyamotoi and of Borreila burgdorferi sensu stricto (ss), the agent of Lyme disease, in western North America. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25333277", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 189, "text": "In France as elsewhere in Europe the most prevalent TBD in humans is Lyme borreliosis, caused by different bacterial species belonging to Borrelia burgdorferi sensu lato complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24886071", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 596, "text": "B. miyamotoi belonging to the relapsing fever group and transmitted by the same Ixodes species has been involved in human disease in Russia, the USA and the Netherlands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24886071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Laboratory diagnosis of Lyme disease is based on the serological detection of antibodies against the etiologic agent Borrelia burgdorferi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24623628", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 357, "text": "B. burgdorferi sl complex, currently comprising at least 19 genospecies, includes the main pathogenic species responsible for human disease in Europe: B. burgdorferi sensu stricto (ss), B. afzelii, and B. garinii. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24533160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The European red squirrel (Sciurus vulgaris) has long been suspected to be a reservoir host of the agents of Lyme borreliosis, in particular B. burgdorferi sensu stricto (s.s.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24446554", "endSection": "abstract" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1765, "text": "n adults (n = 227), the prevalence of infection with B. burgdorferi s.l. was 27.3%, with 18.9% B. burgdorferi s.s., 11.9% B. afzelii, and 3.5% B. garinii. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24446554", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 882, "text": ": The overall estimated prevalence of B. burgdorferi s.l was 9.7% ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23837798", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1342, "text": ". The most prevalent genospecies was B. afzelii which was detected in 53.5% of Borrelia-positive ticks, followed by B. garinii and B. valaisiana with 26.2% and 5.5%, respectively. Also, B. bavariensis and B. burgdorferi s.s. DNA in single I. ricinus ti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23837798", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1279, "text": " Among all the analysed antigens those of B. burgdorferi s.s. were the most frequent cause of immunological reaction, followed by antigens of B. afzelii and B. garinii. Reaction to antigens of B. spielmanii was rarely detected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22742788", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 645, "text": "Overall, 15.8% ticks were infected with B. burgdorferi s. I. Borrelia afzelii (43.1%) was the predominant genospecies, followed by Borrelia valaisiana (14.7%), Borrelia garinii (13.7%) and Borrelia burgdorferi sensu stricto (6.3%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23045802", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1310, "text": "In cases where the genospecies could be identified, B. garinii was most frequently found (8x), followed with B. burgdorferi s.s. (4\u00d7) and B. afzelii (3\u00d7).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "In Europe, Ixodes ricinus is the vector of many pathogens of medical and veterinary relevance, among them Borrelia burgdorferi sensu lato and tick-borne encephalitis virus, which have been the subject of numerous investigations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522688", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1169, "text": "The minimum prevalence of Borrelia burgdorferi sensu lato was 2.5%. Borr. afzelii, Borr. burgdorferi sensu stricto, Borr. garinii, Borr. lusitaniae, and Borr. valaisiana were identified by hybridization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22445929", "endSection": "abstract" } ] }, { "body": "Which thyroid hormone transporter is implicated in thyroid hormone resistance syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21874823", "http://www.ncbi.nlm.nih.gov/pubmed/17132274", "http://www.ncbi.nlm.nih.gov/pubmed/22986150", "http://www.ncbi.nlm.nih.gov/pubmed/21459689", "http://www.ncbi.nlm.nih.gov/pubmed/8421095", "http://www.ncbi.nlm.nih.gov/pubmed/17574009", "http://www.ncbi.nlm.nih.gov/pubmed/9350446", "http://www.ncbi.nlm.nih.gov/pubmed/18334584", "http://www.ncbi.nlm.nih.gov/pubmed/19541799", "http://www.ncbi.nlm.nih.gov/pubmed/21825978", "http://www.ncbi.nlm.nih.gov/pubmed/12946875", "http://www.ncbi.nlm.nih.gov/pubmed/17684393", "http://www.ncbi.nlm.nih.gov/pubmed/17040361", "http://www.ncbi.nlm.nih.gov/pubmed/1422238", "http://www.ncbi.nlm.nih.gov/pubmed/10687857", "http://www.ncbi.nlm.nih.gov/pubmed/24170966", "http://www.ncbi.nlm.nih.gov/pubmed/8115332", "http://www.ncbi.nlm.nih.gov/pubmed/17161330", "http://www.ncbi.nlm.nih.gov/pubmed/9092799", "http://www.ncbi.nlm.nih.gov/pubmed/8594618", "http://www.ncbi.nlm.nih.gov/pubmed/8475937", "http://www.ncbi.nlm.nih.gov/pubmed/7833674", "http://www.ncbi.nlm.nih.gov/pubmed/23392090", "http://www.ncbi.nlm.nih.gov/pubmed/21468521", "http://www.ncbi.nlm.nih.gov/pubmed/18940949", "http://www.ncbi.nlm.nih.gov/pubmed/2885829", "http://www.ncbi.nlm.nih.gov/pubmed/1580595" ], "ideal_answer": [ "thyroid hormone transporter MCT8 is implicated in thyroid hormone resistance syndrome", "Hemizygous MCT8 mutations cuases TH resistance syndrome in males characterized by severe psychomotor retardation, known as the Allan-Herndon-Dudley syndrome (AHDS)." ], "exact_answer": [ "monocarboxylate transporter 8", "TH monocarboxylate transporter 8 (MCT8) mutation is implicated in the TH resistance syndrome", "MCT8" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009914", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011815", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018382", "http://www.disease-ontology.org/api/metadata/DOID:11633", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014186", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ], "type": "factoid", "id": "52ece29f98d023950500002c", "snippets": [ { "offsetInBeginSection": 489, "offsetInEndSection": 732, "text": "Hemizygous MCT8 mutations in males cause severe psychomotor retardation, known as the Allan-Herndon-Dudley syndrome (AHDS), and abnormal serum TH levels. AHDS thus represents a type of TH resistance caused by a defect in cellular TH transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23392090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21468521", "endSection": "title" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1642, "text": "When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg.d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18334584", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 727, "text": "One, producing severe psychomotor defects in > 100 males from 26 families, is caused by mutations in the cell-membrane transporter of TH, MCT8", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574009", "endSection": "abstract" } ] }, { "body": "Which are the subunits of the transcription factor NF-kappaB in the canonical pathway activation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22726116", "http://www.ncbi.nlm.nih.gov/pubmed/17686849", "http://www.ncbi.nlm.nih.gov/pubmed/23636254" ], "ideal_answer": [ "The NF-\u03baB canonical pathway is mediated by the p65/relA and p50 subunits." ], "exact_answer": [ [ "p65", "RelA" ], [ "p50", "NF-\u03baB1" ] ], "type": "list", "id": "5506eca18e1671127b00000f", "snippets": [ { "offsetInBeginSection": 228, "offsetInEndSection": 559, "text": "In this study, we demonstrated that the HSV-1 UL42 protein, a DNA polymerase processivity factor, was a novel antagonism of the canonical NF-\u03baB signaling pathway. UL42 was shown to significantly suppress TNF-\u03b1 mediated NF-\u03baB activation. Co-immunoprecipitation experiment revealed that UL42 bound to the NF-\u03baB subunits p65 and p50. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636254", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1337, "text": "Thus, it was first time we demonstrated that HSV-1 UL42 appeared to prevent NF-\u03baB-dependent gene expression by retaining p65 and p50 in the cytoplasm, and UL42-dependent transcriptional activation were inherently coupled to promote HSV-1 lytic replication, which also may contribute to immune evasion and pathogenesis of HSV-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636254", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 811, "text": "The review describes NF-\u03baB and its two pathways: the canonical, mediated by the p65 and p50 subunits, and the non-canonical, mediated by the subunits RelB, p52 and p50. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726116", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 725, "text": "The function of the TTV open reading frame (ORF) in the nuclear factor kappaB (NF-kappaB) pathway has not yet been established. In this study, we found for the first time that the TTV ORF2 protein could suppress NF-kappaB activity in a dose-dependent manner in the canonical NF-kappaB pathway. By Western blot analysis, we proved that the TTV ORF2 protein did not alter the level of NF-kappaB expression but prevented the p50 and p65 subunits from entering the nucleus due to the inhibition of IkappaBalpha protein degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17686849", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Herpes simplex virus 1 DNA polymerase processivity factor UL42 inhibits TNF-\u03b1-induced NF-\u03baB activation by interacting with p65/RelA and p50/NF-\u03baB1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636254", "endSection": "title" } ] }, { "body": "Is there any link between conserved noncoding elements and alternative splicing in vertebrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24681619" ], "ideal_answer": [ "Yes. Some of the most highly conserved sequences occur in genes encoding RNA binding proteins, particularly the RNA splicing-associated SR genes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017124", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014714", "http://amigo.geneontology.org/amigo/term/GO:0000381", "http://amigo.geneontology.org/amigo/term/GO:0000380" ], "type": "yesno", "id": "56b8ed4b156496395c000004", "snippets": [ { "offsetInBeginSection": 803, "offsetInEndSection": 1245, "text": "Some of the most highly conserved sequences occur in genes encoding RNA binding proteins, particularly the RNA splicing-associated SR genes. Differences in sequence conservation between plants and animals are likely to reflect differences in the biology of the organisms, with plants being much more able to tolerate genomic deletions and whole-genome duplication events due, in part, to their far greater fecundity compared with vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681619", "endSection": "abstract" } ] }, { "body": "Which protein is affected by dusp8 activation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "http://www.ncbi.nlm.nih.gov/pubmed/11313966", "http://www.ncbi.nlm.nih.gov/pubmed/23032483", "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "http://www.ncbi.nlm.nih.gov/pubmed/11948422", "http://www.ncbi.nlm.nih.gov/pubmed/12598532", "http://www.ncbi.nlm.nih.gov/pubmed/23159405" ], "ideal_answer": [ "dusp8 (M3/6) is a dual-specificity phosphatase selective for JNK." ], "exact_answer": [ "JNK" ], "concepts": [ "http://www.uniprot.org/uniprot/DUS8_MOUSE", "http://www.uniprot.org/uniprot/DUS8_HUMAN" ], "type": "factoid", "id": "5148691bd24251bc0500002d", "snippets": [ { "offsetInBeginSection": 1270, "offsetInEndSection": 1417, "text": "Thus, rosiglitazone's neuroprotective effect after ischemia is mediated by blocking JNK phosphorylation induced by ischemia via DUSP8 upregulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23032483", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Prevention of JNK phosphorylation as a mechanism for rosiglitazone in neuroprotection after transient cerebral ischemia: activation of dual specificity phosphatase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23032483", "endSection": "title" }, { "offsetInBeginSection": 1219, "offsetInEndSection": 1337, "text": "These results suggest that JNK activation by H(2)O(2) plus PDTC resulted from the down-regulation of JNK phosphatases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11313966", "endSection": "sections.0" }, { "offsetInBeginSection": 637, "offsetInEndSection": 693, "text": "M3/6 is a dual-specificity phosphatase selective for JNK", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Phosphorylation of the M3/6 dual-specificity phosphatase enhances the activation of JNK by arsenite.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 447, "text": "Dual-specificity phosphatases (DUSPs) play a very important role in these events by modulating the extent of JNK phosphorylation and activation and thus regulating cellular responses to stress. M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "endSection": "sections.0" }, { "offsetInBeginSection": 432, "offsetInEndSection": 536, "text": "Both anisomycin and arsenite activate the JNK pathway and, in addition, inactivate the M3/6 phosphatase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11948422", "endSection": "sections.0" }, { "offsetInBeginSection": 416, "offsetInEndSection": 676, "text": "M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159405", "endSection": "sections.0" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1211, "text": ". We suggest that reduction of HSP70 by expanded polyglutamine is implicated in aggregation and inhibition of M3/6 and in activation of JNK and AP-1.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12598532", "endSection": "sections.0" } ] }, { "body": "Which receptors are targeted by a drug Macitentan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22311911", "http://www.ncbi.nlm.nih.gov/pubmed/22862294", "http://www.ncbi.nlm.nih.gov/pubmed/23192269", "http://www.ncbi.nlm.nih.gov/pubmed/23830395", "http://www.ncbi.nlm.nih.gov/pubmed/24122306", "http://www.ncbi.nlm.nih.gov/pubmed/23984728", "http://www.ncbi.nlm.nih.gov/pubmed/23900878", "http://www.ncbi.nlm.nih.gov/pubmed/23077657", "http://www.ncbi.nlm.nih.gov/pubmed/22458347", "http://www.ncbi.nlm.nih.gov/pubmed/21611927", "http://www.ncbi.nlm.nih.gov/pubmed/21541781", "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "http://www.ncbi.nlm.nih.gov/pubmed/24297706", "http://www.ncbi.nlm.nih.gov/pubmed/22189899", "http://www.ncbi.nlm.nih.gov/pubmed/20730702", "http://www.ncbi.nlm.nih.gov/pubmed/19765655", "http://www.ncbi.nlm.nih.gov/pubmed/21403842", "http://www.ncbi.nlm.nih.gov/pubmed/24122797", "http://www.ncbi.nlm.nih.gov/pubmed/23204120", "http://www.ncbi.nlm.nih.gov/pubmed/23817130", "http://www.ncbi.nlm.nih.gov/pubmed/23353592", "http://www.ncbi.nlm.nih.gov/pubmed/21175577", "http://www.ncbi.nlm.nih.gov/pubmed/24261583", "http://www.ncbi.nlm.nih.gov/pubmed/23568224", "http://www.ncbi.nlm.nih.gov/pubmed/23682110", "http://www.ncbi.nlm.nih.gov/pubmed/22348175", "http://www.ncbi.nlm.nih.gov/pubmed/23068290", "http://www.ncbi.nlm.nih.gov/pubmed/21670421", "http://www.ncbi.nlm.nih.gov/pubmed/22525377", "http://www.ncbi.nlm.nih.gov/pubmed/23829793", "http://www.ncbi.nlm.nih.gov/pubmed/23997048" ], "ideal_answer": [ "Endothelin receptor A and endothelin receptor B are targeted by a drug Macitentan. Macitentan is a potent, orally active, non-peptide dual antagonist of endothelin receptors A and B that is approved for the treatment of pulmonary arterial hypertension." ], "exact_answer": [ [ "endothelin receptor A" ], [ "endothelin receptor B" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004872", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011955", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ], "type": "list", "id": "5335d4e8d6d3ac6a34000053", "snippets": [ { "offsetInBeginSection": 17, "offsetInEndSection": 168, "text": "Macitentan is a novel dual endothelin receptor antagonist with sustained receptor binding in clinical development for pulmonary arterial hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23817130", "endSection": "abstract" }, { "offsetInBeginSection": 63, "offsetInEndSection": 304, "text": "This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23682110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23568224", "endSection": "title" }, { "offsetInBeginSection": 27, "offsetInEndSection": 243, "text": "Macitentan is a potent, orally active, non-peptide antagonist of endothelin receptors with tissue-targeting properties, currently undergoing clinical development for the treatment of pulmonary arterial hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23568224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Interaction profile of macitentan, a new non-selective endothelin-1 receptor antagonist, in vitro.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23353592", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Macitentan is a new non-selective endothelin-1 receptor antagonist under development for the treatment of pulmonary arterial hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23353592", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 796, "text": "This article highlights how the introduction of new compounds such as macitentan, riociguat and selexipag, which act on the endothelin, nitric oxide and prostacyclin pathways, respectively, have the potential to further improve the prognosis for patients with PAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204120", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 503, "text": "Dual ETRA/ETRB blockade with macitentan (or the combination of the ETRA and ETRB antagonists BQ123 and BQ788) did not enhance antitumor immune cell recruitment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23192269", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 433, "text": "The novel ERA macitentan has recently concluded testing in a Phase III morbidity/mortality clinical trial in PAH patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077657", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 781, "text": "Given that the newest PAH drugs include a receptor tyrosine kinase antagonist (imatinib), a soluble guanylate cyclase stimulator (riociguat), an oral analog of prostacyclin (selexipag), and a tissue targeting ERA (macitentan) determination of appropriate combinations for various etiologies and clinical stages is urgently required. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23068290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22862294", "endSection": "title" }, { "offsetInBeginSection": 285, "offsetInEndSection": 572, "text": "Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ET(A) with significant affinity for the ET(B) receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22862294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525377", "endSection": "title" }, { "offsetInBeginSection": 230, "offsetInEndSection": 386, "text": "Here we investigated the effects of macitentan, an orally-active, tissue-targeting dual ET receptor antagonist on chronic complications in type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525377", "endSection": "abstract" }, { "offsetInBeginSection": 2936, "offsetInEndSection": 3233, "text": "Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan, macitentan soon available) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23829793", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1229, "text": "The aim of the present study is to evaluate the in vitro effect of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist, and its major metabolite (ACT-132577) on alpha smooth muscle actin (alphaSMA) expression, evaluated on dermal fibroblasts from healthy subjects and on dermal fibroblasts from lesional and non-lesional skin from sclerodermic patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830395", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple-dose study in healthy subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23900878", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "This multiple-ascending-dose study investigated safety, tolerability, pharmacokinetics, and pharmacodynamics, of macitentan, a new endothelin receptor antagonist (ERA) with sustained receptor binding and enhanced tissue penetration properties compared to other ERAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23900878", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 324, "text": "We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23984728", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 866, "text": "Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997048", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 967, "text": "Promising candidates include tyrosine kinase antagonists (e.g. imatinib); soluble guanylate cyclase stimulators (riociguat); an oral analog of prostacyclin (selexipag); and a tissue targeting endothelin receptor antagonist (macitentan).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24122306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Pharmacokinetics of the novel dual endothelin receptor antagonist macitentan in subjects with hepatic or renal impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24122797", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24261583", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 116, "text": "Macitentan is a novel dual endothelin receptor antagonist (ERA) showing sustained receptor occupancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24261583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Macitentan (Opsumit\u00ae) is a novel dual endothelin receptor antagonist (ERA) with sustained receptor binding properties developed by Actelion Pharmaceuticals Ltd. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297706", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 698, "text": "Endothelin (ET)-1 influences pathological changes via two ET receptor subtypes (ETA and ETB), to which it binds with high affinity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297706", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1359, "text": "Macitentan was developed by modifying the structure of bosentan in the search for an optimal dual ERA with improved efficacy and tolerability compared with other ERAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22458347", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Macitentan is a tissue-targeting, dual endothelin receptor antagonist, currently under phase 3 investigation in pulmonary arterial hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22458347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Antivascular therapy for multidrug-resistant ovarian tumors by macitentan, a dual endothelin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22348175", "endSection": "title" }, { "offsetInBeginSection": 619, "offsetInEndSection": 806, "text": "The nonselective endothelin type A and B receptor antagonists bosentan (100 nmol/L) and macitentan (30 nmol/L) alone relaxed endothelin-contracted rings by 30\u00b15% and 24\u00b13%, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22311911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Macitentan is a dual endothelin receptor antagonist under phase 3 investigation in pulmonary arterial hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22189899", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1387, "text": "This rise could largely be prevented with the endothelin receptor antagonist macitentan (\u0394BP: 12.3\u00b11.5 mm Hg) and only mildly with Tempol, a superoxide dismutase mimetic (\u0394BP: 25.9\u00b12.3 mm Hg). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21670421", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 643, "text": "Promising study results for the treatment of IPF were published for the triple tyrosine kinase inhibitor intedanib, other drugs such as the endothelin receptor antagonist (ERA) macitentan are currently investigated in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21611927", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 174, "text": "To study the pharmacokinetics, pharmacodynamics, and tolerability of rising single doses of macitentan, an endothelin receptor antagonist, in healthy male subjects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21541781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Macitentan (ACT-064992), a tissue-targeting endothelin receptor antagonist, enhances therapeutic efficacy of paclitaxel by modulating survival pathways in orthotopic models of metastatic human ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403842", "endSection": "title" }, { "offsetInBeginSection": 184, "offsetInEndSection": 354, "text": "We investigated the therapeutic efficacy of the dual ETR antagonist, macitentan, on human ovarian cancer cells, SKOV3ip1 and IGROV1, growing orthotopically in nude mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Macitentan, a tissue-targeting endothelin receptor antagonist for the potential oral treatment of pulmonary arterial hypertension and idiopathic pulmonary fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730702", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Macitentan (ACT-064992), under development by Actelion Ltd in collaboration with Japanese licensee Nippon Shinyaku Co Ltd, is an orally active, non-peptide dual endothelin (ET)(A) and ET(B) receptor antagonist for the potential treatment of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730702", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 836, "text": "Macitentan, because of its ability to target the tissues and to block both ET(A) and ET(B) receptors, is emerging as a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19765655", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Macitentan (ACT-064992) is an orally active endothelin receptor antagonist. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19765655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Macitentan, also called Actelion-1 or ACT-064992 [N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-N'-propylaminosulfonamide], is a new dual ET(A)/ET(B) endothelin (ET) receptor antagonist designed for tissue targeting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 1013, "text": "Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET(A) receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET(B) receptors). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1560, "text": "In conclusion, macitentan, by its tissue-targeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "abstract" } ] }, { "body": "What is known as the cause of subacute thyroiditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19497087", "http://www.ncbi.nlm.nih.gov/pubmed/22819125", "http://www.ncbi.nlm.nih.gov/pubmed/16284433" ], "ideal_answer": [ "Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus" ], "type": "summary", "id": "51406d6923fec90375000007", "snippets": [ { "offsetInBeginSection": 95, "offsetInEndSection": 241, "text": "Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819125", "endSection": "sections.0" } ] }, { "body": "Which drugs are utilized to treat eosinophilic esophagitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19533356", "http://www.ncbi.nlm.nih.gov/pubmed/22475741", "http://www.ncbi.nlm.nih.gov/pubmed/22561055", "http://www.ncbi.nlm.nih.gov/pubmed/20457157", "http://www.ncbi.nlm.nih.gov/pubmed/23011019", "http://www.ncbi.nlm.nih.gov/pubmed/23478244", "http://www.ncbi.nlm.nih.gov/pubmed/21277394" ], "ideal_answer": [ "Therapeutic options of eosinophilic esophagitis include use of proton-pump inhibitors, immunosuppressive drugs, elimination diets, and esophageal dilatation.\nOral viscous budesonide (OVB) is an effective treatment of pan-esophageal disease in children with EoE. OVB improves symptoms and endoscopic and histologic features." ], "exact_answer": [ [ "proton pump inhibitors" ], [ "immunosoppressive drugs" ], [ "budesonide" ] ], "type": "list", "id": "518ba4b5310faafe08000005", "snippets": [ { "offsetInBeginSection": 722, "offsetInEndSection": 859, "text": "Current therapeutic options include use of proton-pump inhibitors, immunosuppressive drugs, elimination diets, and esophageal dilatation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23478244", "endSection": "sections.0" }, { "offsetInBeginSection": 1713, "offsetInEndSection": 1819, "text": "Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475741", "endSection": "sections.0" }, { "offsetInBeginSection": 1556, "offsetInEndSection": 1806, "text": "OVB is an effective treatment of pan-esophageal disease in children with EoE. OVB improves symptoms and endoscopic and histologic features. Proton pump inhibitor single therapy did not significantly improve esophageal eosinophilia or symptoms of EoE.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20457157", "endSection": "sections.0" } ] }, { "body": "What is the incidence of cystic fibrosis in the caucasian population?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11948988", "http://www.ncbi.nlm.nih.gov/pubmed/15211979", "http://www.ncbi.nlm.nih.gov/pubmed/7513296", "http://www.ncbi.nlm.nih.gov/pubmed/1722259", "http://www.ncbi.nlm.nih.gov/pubmed/19787152", "http://www.ncbi.nlm.nih.gov/pubmed/659256", "http://www.ncbi.nlm.nih.gov/pubmed/2999612", "http://www.ncbi.nlm.nih.gov/pubmed/22989055", "http://www.ncbi.nlm.nih.gov/pubmed/20034372", "http://www.ncbi.nlm.nih.gov/pubmed/7509311", "http://www.ncbi.nlm.nih.gov/pubmed/17968991", "http://www.ncbi.nlm.nih.gov/pubmed/15698945", "http://www.ncbi.nlm.nih.gov/pubmed/7635469", "http://www.ncbi.nlm.nih.gov/pubmed/1756602", "http://www.ncbi.nlm.nih.gov/pubmed/18078202", "http://www.ncbi.nlm.nih.gov/pubmed/2570015", "http://www.ncbi.nlm.nih.gov/pubmed/10992696", "http://www.ncbi.nlm.nih.gov/pubmed/18344710", "http://www.ncbi.nlm.nih.gov/pubmed/1392366", "http://www.ncbi.nlm.nih.gov/pubmed/1281842", "http://www.ncbi.nlm.nih.gov/pubmed/1683481" ], "ideal_answer": [ "Estimates of the newborn frequency of cystic fibrosis in different Caucasian groups range from 4 times more to 40 times less common than the generally accepted figure of 1:2000.", "Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000-1/2,500 live births, but the actual estimate varies with the geographic location." ], "exact_answer": [ "1:2000" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015994", "http://www.disease-ontology.org/api/metadata/DOID:1485", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003550" ], "type": "factoid", "id": "56c3320a50c68dd416000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Estimates of the newborn frequency of cystic fibrosis in different Caucasian groups range from 4 times more to 40 times less common than the generally accepted figure of 1:2000.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/659256", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 412, "text": "Current meconium screening trials which may be effective in populations with the incidence equal to or greater than 1:2000, may be useful for populations with an incidence as low as 1:7000 only after maximum improvement of the methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/659256", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 319, "text": "Studies on migrant Indian population in United States and United Kingdom estimate frequency of CF as 1:10,000 to 1:40,000", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17968991", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 975, "text": "The frequency of common mutation F508del in Indian children is between 19% and 34%. Other mutations are heterogeneous", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17968991", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 623, "text": "The delta F508 mutation was found in 9 cases (60%), of which 5 were homozygous for the disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10992696", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 664, "text": "The disease frequency varies considerably among the latter. Among Ashkenazi Jews, the frequency of CF is 1:3300, which is similar to the frequency in most Caucasian populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7635469", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 373, "text": "Although no careful scientific study had ever been done the impression was that CF was extremely rare among the Greek-Cypriots, with an incidence estimated at around 1:30,000", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7513296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The incidence of cystic fibrosis (CF) in Finland, 1:25,000 newborn, is one of the lowest in Caucasian populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7509311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disorder in Caucasian populations, with an incidence of about 1 in 2000 live births, implying a carrier frequency of about 1 in 22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1683481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "The incidence of cystic fibrosis (CF) in Finland is one tenth that in other Caucasian populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2570015", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 317, "text": "In Denmark the incidence of cystic fibrosis is 1:4700, which is quite low compared to other European countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1392366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Cystic fibrosis is the most frequent autosomal recessive disease in the Caucasian population, with an incidence of 1:2500 newborn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22989055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Cystic fibrosis (CF) is the commonest autosomal recessive condition among Caucasian populations, affecting 1 in 2500 live births.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20034372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disorder in Caucasian populations, with an incidence of about 1 in 2000 live births", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1683481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000 newborns but the actual estimate varies with the geographic location. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1722259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Cystic fibrosis (CF) is an autosomal recessive disorder with a prevalence at birth estimated at 1/2000-1/2500 livebirths in Caucasian populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1756602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Cystic fibrosis is one of the most common autosomal recessive hereditary diseases in the Caucasian population, with an incidence of 1:2000 to 1:3500 liveborns", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19787152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Cystic fibrosis (CF) is the most common autosomal recessive disease in the European (Caucasian) population, with an incidence of 1:2000 to 1:8000", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18078202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Cystic fibrosis (CF) is the most common genetic disease in Caucasian populations, with an incidence of 1 in 2,000 live births in the United Kingdom, and a carrier frequency of approximately 1 in 20", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2999612", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 578, "text": "Current meconium screening trials which may be effective in populations with the incidence equal to or greater than 1:2000, may be useful for populations with an incidence as low as 1:7000 only after maximum improvement of the methods. Once the true incidence or the variable incidence is proven for Caucasian populations, screening trails in Negro, Oriental and Indian populations will be required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/659256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasian populations. The generally accepted incidence of CF in the United States is 1 in 3,200 in the Caucasian population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11948988", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 381, "text": "In this region, it has been documented that the incidence of cystic fibrosis reached 1/902 live births between 1975 and 1988, three times higher than the average incidence of 1/2500 live births reported in other Caucasian populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18344710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000 newborns but the actual estimate varies with the geographic location. The incidence of CF in non-Caucasian populations is low.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1722259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Cystic fibrosis is the most frequent autosomal recessive disease in the Caucasian population, with an incidence of 1:2500 newborn and a frequency of 1:25", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22989055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Cystic fibrosis (CF) is the most common lethal inherited disease in the Caucasian population with an incidence of approximately 1 in 2,500 live births", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1281842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Cystic Fibrosis (CF) is the most common and severe autosomal recessive disease in Caucasian populations, with an incidence of 1 in 2500 live births. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15211979", "endSection": "abstract" } ] }, { "body": "What is the effect of thapsigargin treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26154615", "http://www.ncbi.nlm.nih.gov/pubmed/26018251", "http://www.ncbi.nlm.nih.gov/pubmed/25899321", "http://www.ncbi.nlm.nih.gov/pubmed/25827060", "http://www.ncbi.nlm.nih.gov/pubmed/26137860", "http://www.ncbi.nlm.nih.gov/pubmed/26086109", "http://www.ncbi.nlm.nih.gov/pubmed/26034200", "http://www.ncbi.nlm.nih.gov/pubmed/26034201", "http://www.ncbi.nlm.nih.gov/pubmed/25779646", "http://www.ncbi.nlm.nih.gov/pubmed/26055788", "http://www.ncbi.nlm.nih.gov/pubmed/25896661", "http://www.ncbi.nlm.nih.gov/pubmed/25878248" ], "triples": [ { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin", "o": "67526-95-8" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin", "o": "Thapsigargin" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1260017", "o": "http://linkedlifedata.com/resource/umls/id/C0076374" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0076374", "o": "http://linkedlifedata.com/resource/umls/label/A18001764" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0076374", "o": "http://linkedlifedata.com/resource/umls/label/A0233024" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17953819", "o": "Thapsigargin [Chemical/Ingredient]" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0076374", "o": "http://linkedlifedata.com/resource/umls/label/A0806191" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0076374", "o": "http://linkedlifedata.com/resource/umls/label/A18001764" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0076374", "o": "http://linkedlifedata.com/resource/umls/label/A17953819" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2788684", "o": "L12ADT" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18001764", "o": "Thapsigargin" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0233024", "o": "thapsigargin" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C0296378", "o": "http://linkedlifedata.com/resource/umls/id/C0076374" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0595935", "o": "dansylthapsigargin" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0806191", "o": "D019284" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0806191", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0233024", "o": "4006-0091" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17953819", "o": "N0000166351" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18001764", "o": "N0000166351" } ], "ideal_answer": [ "Thapsigargin is an endoplasmic stress inducer. \tIt is a sarcoplasmic/endoplasmic Ca(2+)-ATPase (SERCA) inhibitor." ], "exact_answer": [ "Thapsigargin is a sarcoplasmic/endoplasmic Ca(2+)-ATPase (SERCA) inhibitor." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019284", "http://www.biosemantics.org/jochem#4250351" ], "type": "factoid", "id": "56b7210b76d8bf8d13000004", "snippets": [ { "offsetInBeginSection": 1098, "offsetInEndSection": 1173, "text": " the sarcoplasmic/endoplasmic Ca(2+)-ATPase (SERCA) inhibitor thapsigargin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26034200", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 620, "text": "Treatment of endoplasmic stress inducers, thapsigargin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25896661", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 904, "text": "the two unrelated reversible autophagy inhibitors 3-methyladenine (3MA) and thapsigargin (TG) both blocked cargo sequestration completely.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25779646", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1043, "text": "pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26154615", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 684, "text": " pharmacological ER stress agents (thapsigargin and tunicamycin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26086109", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1479, "text": " thapsigargin-induced calcium depletion of sarcoplasmic reticular stores", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26034201", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 958, "text": "Addition of thapsigargin (Tg), that induces store-depletion and activates TRPC1-mediated Ca(2+) entry, potentiated the Cl(-) current, which was inhibited by the addition of a non-specific TRPC channel blocker SKF96365 or removal of external Ca(2+).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899321", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 538, "text": "we demonstrate that thapsigargin (TG) and tunicamycin (TM), two ERS inducers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827060", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 900, "text": "hapsigargin, a sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) Ca(2+) pump inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25878248", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1276, "text": "Thapsigargin-induced ER stress ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26018251", "endSection": "abstract" }, { "offsetInBeginSection": 1552, "offsetInEndSection": 1584, "text": "SERCA2a inhibitor (thapsigargin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26055788", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1065, "text": "he ER stressors, thapsigargin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137860", "endSection": "abstract" } ] }, { "body": "What is the Her2 status in Li-Fraumeni syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23580068", "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "http://www.ncbi.nlm.nih.gov/pubmed/22878818", "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "http://www.ncbi.nlm.nih.gov/pubmed/22392042" ], "ideal_answer": [ "In the background of a germline TP53 mutation of the Li-Fraumeni syndrome, the Her2 status was found to be positive in 63-83% of the cases." ], "exact_answer": [ "Her2 status is positive" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3012", "http://www.disease-ontology.org/api/metadata/DOID:0060079", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018734", "http://www.uniprot.org/uniprot/ERBB2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0038128", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016864" ], "type": "factoid", "id": "5318929fb166e2b80600001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Prevalence of germline TP53 mutations in HER2+ breast cancer patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580068", "endSection": "title" }, { "offsetInBeginSection": 158, "offsetInEndSection": 257, "text": "Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2+ (63-83 %).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580068", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 818, "text": "As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22878818", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 403, "text": "Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392042", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1104, "text": "The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392042", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1399, "text": "Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392042", "endSection": "abstract" }, { "offsetInBeginSection": 1682, "offsetInEndSection": 1782, "text": "Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Early onset HER2-positive breast cancer is associated with germline TP53 mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "endSection": "title" }, { "offsetInBeginSection": 614, "offsetInEndSection": 895, "text": "Patients who tested positive for germlineTP53 mutations (n = 30) were compared with controls (n = 79). Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared with 25% for the controls (P = .0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "endSection": "abstract" }, { "offsetInBeginSection": 1445, "offsetInEndSection": 1556, "text": "This study suggests an association between germline TP53 mutations and early onset HER2-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 143, "text": "The Li-Fraumeni Syndrome is caused by a germline TP53 mutation and is associated with a high risk of breast cancer at young ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1037, "text": "Patients carrying a TP53 mutation showed a significantly higher likelihood of developing a breast cancer with Human Epidermal growth factor Receptor (HER2) amplification (83%) when compared to the cohort of young onset breast cancer cases (16%);", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "abstract" }, { "offsetInBeginSection": 1099, "offsetInEndSection": 1253, "text": "These findings suggest that breast cancer developing on a background of an inherited TP53 mutation is highly likely to present with amplification of HER2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "abstract" } ] }, { "body": "Where is X-ray free electron laser used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23331310", "http://www.ncbi.nlm.nih.gov/pubmed/21293374", "http://www.ncbi.nlm.nih.gov/pubmed/21293373", "http://www.ncbi.nlm.nih.gov/pubmed/22575364", "http://www.ncbi.nlm.nih.gov/pubmed/22975810", "http://www.ncbi.nlm.nih.gov/pubmed/22893239", "http://www.ncbi.nlm.nih.gov/pubmed/21230665", "http://www.ncbi.nlm.nih.gov/pubmed/23214818", "http://www.ncbi.nlm.nih.gov/pubmed/22330507", "http://www.ncbi.nlm.nih.gov/pubmed/23031037", "http://www.ncbi.nlm.nih.gov/pubmed/23396131", "http://www.ncbi.nlm.nih.gov/pubmed/23196907", "http://www.ncbi.nlm.nih.gov/pubmed/22653729", "http://www.ncbi.nlm.nih.gov/pubmed/21500720", "http://www.ncbi.nlm.nih.gov/pubmed/22665786", "http://www.ncbi.nlm.nih.gov/pubmed/21517525", "http://www.ncbi.nlm.nih.gov/pubmed/16642197", "http://www.ncbi.nlm.nih.gov/pubmed/22278059", "http://www.ncbi.nlm.nih.gov/pubmed/23250067", "http://www.ncbi.nlm.nih.gov/pubmed/21190672", "http://www.ncbi.nlm.nih.gov/pubmed/23263128", "http://www.ncbi.nlm.nih.gov/pubmed/22355576", "http://www.ncbi.nlm.nih.gov/pubmed/22714377", "http://www.ncbi.nlm.nih.gov/pubmed/22684196", "http://www.ncbi.nlm.nih.gov/pubmed/22852678", "http://www.ncbi.nlm.nih.gov/pubmed/23083249", "http://www.ncbi.nlm.nih.gov/pubmed/23281652", "http://www.ncbi.nlm.nih.gov/pubmed/22565760", "http://www.ncbi.nlm.nih.gov/pubmed/23031030", "http://www.ncbi.nlm.nih.gov/pubmed/23412482", "http://www.ncbi.nlm.nih.gov/pubmed/11390993", "http://www.ncbi.nlm.nih.gov/pubmed/23291355", "http://www.ncbi.nlm.nih.gov/pubmed/22286383", "http://www.ncbi.nlm.nih.gov/pubmed/20164644", "http://www.ncbi.nlm.nih.gov/pubmed/23003992", "http://www.ncbi.nlm.nih.gov/pubmed/22181929" ], "ideal_answer": [ "X-ray free electron laser (XFEL) technologies provide coherent and extremely intense photon pulses of short duration. XFELs are particularly useful in structural biology and imaging, in structural studies of single biological macromolecules (e.g. high resolution protein structure determination) and assemblies (e.g. viruses) or nanocrystals, which are not amenable to investigation with traditional crystallographic methods. Moreover, XFELs have the potential to be used for studying enzyme kinetics." ], "exact_answer": [ [ "high resolution protein structure determination" ], [ "molecular imaging", "single-particle imaging" ], [ "study of enzyme kinetics", "time resolved protein crystallography" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056928", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018360", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004583", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014965", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007834", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014961" ], "type": "list", "id": "51475d5cd24251bc0500001b", "snippets": [ { "offsetInBeginSection": 662, "offsetInEndSection": 980, "text": "In conjunction with the XFEL temporal profile and high-flux, it is a powerful tool for studying the dynamics of time-dependent systems. Photo-induced processes and fast catalytic reaction kinetics, ranging from femtoseconds to milliseconds, will be resolvable in a wide array of systems circumventing radiation damage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22852678", "endSection": "sections.0" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1711, "text": "We discuss the pertinent physics of the intense X-ray-matter interactions, and illustrate the importance of electron-ion collisions. Detailed simulations of the interaction process conducted with a radiative-collisional code show good qualitative agreement with the experimental results. We obtain insights into the evolution of the charge state distribution of the system, the electron density and temperature, and the timescales of collisional processes. Our results should inform future high-intensity X-ray experiments involving dense samples, such as X-ray diffractive imaging of biological systems, material science investigations, and the study of matter in extreme conditions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22278059", "endSection": "sections.0" }, { "offsetInBeginSection": 449, "offsetInEndSection": 693, "text": "employment of \"exotic\" systems, such as the Free Electron LASER (FEL), that are expected to focus on the fundamental processes of life, following chemical reactions and biological processes as they happen, on unprecedented time and size scales.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21500720", "endSection": "sections.0" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1062, "text": "New data analysis approaches are outlined for the correlated fluctuations in fast WAXS, for protein nanocrystals just a few molecules on a side, and for the continuous x-ray scattering from a single virus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975810", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 601, "text": "Research opportunities and techniques are reviewed for the application of hard x-ray pulsed free-electron lasers (XFEL) to structural biology. These include the imaging of protein nanocrystals, single particles such as viruses, pump--probe experiments for time-resolved nanocrystallography, and snapshot wide-angle x-ray scattering (WAXS) from molecules in solution. The use of femtosecond exposure times, rather than freezing of samples, as a means of minimizing radiation damage is shown to open up new opportunities for the molecular imaging of biochemical reactions at room temperature in solution", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975810", "endSection": "sections.0" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1589, "text": "New opportunities for solving the phase problem for XFEL data are outlined. A summary of the latest results is given, which now extend to atomic resolution for nanocrystals. Possibilities for time-resolved chemistry using fast WAXS (solution scattering) from mixtures is reviewed, toward the general goal of making molecular movies of biochemical processes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22975810", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Molecular imaging using X-ray free-electron lasers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23331310", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The recent development of X-ray free-electron laser sources has created new opportunities for the structural analysis of protein nanocrystals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23250067", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "X-ray free electron lasers hold the promise of enabling atomic-resolution diffractive imaging of single biological molecules.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23003992", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22714377", "endSection": "sections.0" }, { "offsetInBeginSection": 575, "offsetInEndSection": 795, "text": "In this paper we report room temperature X-ray diffraction data of PS\u00a0II microcrystals obtained using ultrashort (<\u00a050\u00a0fs) 9\u00a0keV X-ray pulses from a hard X-ray free electron laser, namely the Linac Coherent Light Source.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665786", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "High-resolution protein structure determination by serial femtosecond crystallography", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22653729", "endSection": "title" }, { "offsetInBeginSection": 210, "offsetInEndSection": 479, "text": "We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22653729", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22286383", "endSection": "sections.0" }, { "offsetInBeginSection": 490, "offsetInEndSection": 760, "text": "Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21293374", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Single mimivirus particles intercepted and imaged with an X-ray laser", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21293374", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Femtosecond X-ray protein nanocrystallography", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21293373", "endSection": "title" }, { "offsetInBeginSection": 548, "offsetInEndSection": 912, "text": "Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21293373", "endSection": "sections.0" }, { "offsetInBeginSection": 711, "offsetInEndSection": 955, "text": "These methods can be used to image biological and materials science samples at high resolution with x-ray undulator radiation and establishes the techniques to be used in atomic-resolution ultrafast imaging at x-ray free-electron laser sources.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16642197", "endSection": "sections.0" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1258, "text": "With the prospects of the x-ray free electron lasers, this approach could provide a major new opportunity for the high-resolution three-dimensional structure determination of single biomolecules.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11390993", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "X-ray free-electron lasers (XFELs) generate sequences of ultra-short spatially coherent pulses of X-ray radiation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23412482", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Diffractive imaging using the intense and coherent beam of X-ray free-electron lasers opens new perspectives for structural studies of single nanoparticles and biomolecules.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23396131", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The opening of hard X-ray free-electron laser facilities, such as the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory in the United States, has ushered in a new era in structural determination.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23331310", "endSection": "sections.0" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1043, "text": "Where possible we also highlight areas that we think could push this field forward with emerging technologies, such as X-ray free electron lasers (X-feL), which could have a big impact on the membrane protein structural biology community.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23291355", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "X-ray free electron lasers (XFELs) deliver short (<100 fs) and intense (\u223c10(12) photons) pulses of hard X-rays, making them excellent sources for time-resolved studies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23281652", "endSection": "sections.0" }, { "offsetInBeginSection": 248, "offsetInEndSection": 474, "text": "Modern imaging techniques at the molecular scale rely on utilizing novel coherent light sources like X-ray free electron lasers for the ultimate goal of visualizing such objects as individual biomolecules rather than crystals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23263128", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "In single-particle coherent x-ray diffraction imaging experiments, performed at x-ray free-electron lasers (XFELs), samples are exposed to intense x-ray pulses to obtain single-shot diffraction patterns.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23214818", "endSection": "sections.0" }, { "offsetInBeginSection": 619, "offsetInEndSection": 884, "text": "The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the \"diffraction-before-destruction\" approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196907", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Coherent diffraction imaging (CDI) of single molecules at atomic resolution is a major goal for the x-ray free-electron lasers (XFELs).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23031037", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Ultrashort X-ray pulses from free-electron laser X-ray sources make it feasible to conduct small- and wide-angle scattering experiments on biomolecular samples in solution at sub-picosecond timescales.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22893239", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The short and intense pulses of the new X-ray free electron lasers, now operational or under construction, may make possible diffraction experiments on single molecule-sized objects with high resolution, before radiation damage destroys the sample.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22575364", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "The recent development of x-ray free electron lasers providing coherent, femtosecond-long pulses of high brilliance and variable energy opens new areas of scientific research in a variety of disciplines such as physics, chemistry, and biology.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22565760", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22286383", "endSection": "sections.0" }, { "offsetInBeginSection": 171, "offsetInEndSection": 330, "text": "X-ray free-electron lasers (FELs) show promise for revealing the structure of single molecules or nanocrystals, but the phase problem remains largely unsolved.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22181929", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Coherent diffractive imaging using x-ray free-electron lasers (XFELs) may provide a unique opportunity for high-resolution structural analysis of single particles sprayed from an aqueous solution into the laser beam.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21517525", "endSection": "sections.0" }, { "offsetInBeginSection": 548, "offsetInEndSection": 807, "text": "Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21293373", "endSection": "sections.0" }, { "offsetInBeginSection": 639, "offsetInEndSection": 901, "text": "This work is directly relevant to the time-resolved imaging of magnetic dynamics using coherent and ultrafast radiation from x-ray free-electron lasers and also to broader classes of diffractive imaging experiments which suffer noisy data, missing data, or both.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21230665", "endSection": "sections.0" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1296, "text": "By combining serial nanocrystallography with x-ray free-electron laser sources in the future, it may be possible to produce molecular-resolution electron-density maps using membrane protein crystals that contain only a few hundred or thousand unit cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21190672", "endSection": "sections.0" }, { "offsetInBeginSection": 707, "offsetInEndSection": 884, "text": "Very strong soft X-ray free electron laser (FEL) pulses must be short to allow for investigations of ultra-fast wet chemistry, according to the principle of collect and destroy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22684196", "endSection": "sections.0" } ] }, { "body": "Which protein kinases have been found to phosphorylate Phospholamban and affect its biological activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22463608", "http://www.ncbi.nlm.nih.gov/pubmed/22707725", "http://www.ncbi.nlm.nih.gov/pubmed/19696029", "http://www.ncbi.nlm.nih.gov/pubmed/19671701", "http://www.ncbi.nlm.nih.gov/pubmed/20060004", "http://www.ncbi.nlm.nih.gov/pubmed/20349314", "http://www.ncbi.nlm.nih.gov/pubmed/22772476", "http://www.ncbi.nlm.nih.gov/pubmed/2544595", "http://www.ncbi.nlm.nih.gov/pubmed/25451386" ], "ideal_answer": [ "Phosphorylation of phospholamban at Ser16 is mainly mediated by PKA and at Thr17 by Ca(2+) /calmodulin-dependent protein kinase (CaMKII). Phospholamban is also a reporter for PKG activity and akt kinase interacts with and phosphorylates PLN at Thr(17)." ], "exact_answer": [ [ "protein kinase A", "PKA" ], [ "protein kinase G", "PKG" ], [ "Ca(2+) /calmodulin-dependent protein kinase II", "CaMKII" ], [ "akt kinase", "Akt" ] ], "type": "list", "id": "54db7c4ac0bb8dce23000001", "snippets": [ { "offsetInBeginSection": 520, "offsetInEndSection": 706, "text": "Dephosphorylated PLN is an inhibitor of SERCA2a and phosphorylation by protein kinase A (PKA) or calcium-calmodulin-dependent protein kinases (CAMKII) relieves these inhibitory effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451386", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 945, "text": "We have found that phosphorylation of PLN by protein kinase A (PKA) leads to an increase in the rate of Ca(2+) leak from Ca(2+)-loaded SR vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22772476", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 724, "text": "PKG activity of cardiac myocytes was assessed by phospholamban (PLB) phosphorylation determined by western blot. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20349314", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1315, "text": "PLB is not a unique reporter for PKG activity since it is also phosphorylated by protein kinase A (PKA), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20349314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) plays an important role mediating apoptosis/necrosis during ischemia-reperfusion (IR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20060004", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 516, "text": "The onset of reperfusion increased the phosphorylation of Thr(17) site of phospholamban, without changes in total protein, consistent with an increase in CaMKII activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20060004", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1308, "text": "We found that when activated, Akt interacts with and phosphorylates PLN at Thr(17), the Ca(2+)-calmodulin-dependent kinase IIdelta site, whereas silencing Akt signaling, through the knock-out of phosphatidylinositol-dependent kinase-1, resulted in reduced phosphorylation of PLN at Thr(17). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19696029", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 642, "text": "Deletion of Arg(14) disrupts the protein kinase A recognition motif, which abrogates phospholamban phosphorylation and results in constitutive SERCA inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707725", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 345, "text": "Dephosphorylated PLN tonically inhibits the SR Ca-ATPase (SERCA2a), while phosphorylation at Ser16 by PKA and Thr17 by Ca(2+) /calmodulin-dependent protein kinase (CaMKII) relieves the inhibition, and this increases SR Ca(2+) uptake. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22463608", "endSection": "abstract" }, { "offsetInBeginSection": 784, "offsetInEndSection": 1030, "text": "Both CaMKIIdelta(C) and the novel CaMKIIbeta(4) isoforms were found to exist in complex with alphaKAP and SERCA2a at the SR and were able to phosphorylate Thr-17 on phospholamban (PLN), an accessory subunit and known regulator of SERCA2a activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19671701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "Phospholamban is the major membrane protein of the heart phosphorylated in response to beta-adrenergic stimulation. In cell-free systems, cAMP-dependent protein kinase catalyzes exclusive phosphorylation of serine 16 of phospholamban, whereas Ca2+/calmodulin-dependent protein kinase gives exclusive phosphorylation of threonine 17 (Simmerman, H. K. B., Collins, J. H., Theibert, J. L., Wegener, A. D., and Jones, L. R. (1986) J. Biol. Chem. 261, 13333-13341).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2544595", "endSection": "abstract" } ] }, { "body": "Why can't humans synthesize Neu5Gc (N-Glycolylneuraminic acid)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25003133", "http://www.ncbi.nlm.nih.gov/pubmed/25124893", "http://www.ncbi.nlm.nih.gov/pubmed/18971931", "http://www.ncbi.nlm.nih.gov/pubmed/18669916", "http://www.ncbi.nlm.nih.gov/pubmed/24505439", "http://www.ncbi.nlm.nih.gov/pubmed/23520510", "http://www.ncbi.nlm.nih.gov/pubmed/16806174", "http://www.ncbi.nlm.nih.gov/pubmed/22390546", "http://www.ncbi.nlm.nih.gov/pubmed/20452577", "http://www.ncbi.nlm.nih.gov/pubmed/25517696", "http://www.ncbi.nlm.nih.gov/pubmed/15972653", "http://www.ncbi.nlm.nih.gov/pubmed/24829344", "http://www.ncbi.nlm.nih.gov/pubmed/19156207" ], "ideal_answer": [ "N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid synthesized by animals, but not by humans or birds. Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. Losing this sugar changed how humans interact with some of our deadliest pathogens: malaria, influenza, and streptococcus among others." ], "type": "summary", "id": "57152ebbcb4ef8864c000002", "snippets": [ { "offsetInBeginSection": 755, "offsetInEndSection": 1008, "text": "Human muscle from normal (no evident disease, n\u200a=\u200a3), Becker (BMD, n\u200a=\u200a3) and Duchenne (DMD, n\u200a=\u200a3) muscular dystrophy individuals had absent to very low Neu5Gc staining, but some punctate intracellular muscle staining was present in BMD and DMD muscles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24505439", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 115, "text": "N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid synthesized by animals, but not by humans or birds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003133", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 387, "text": "Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. Losing this sugar changed how humans interact with some of our deadliest pathogens: malaria, influenza, and streptococcus among others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25124893", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 399, "text": "Anti-Neu5Gc antibodies are detected in all human sera, though with variable levels and epitope-recognition profiles. These antibodies likely play a role in several inflammation-mediated pathologies including cardiovascular diseases and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23520510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Human polyclonal IgG antibodies directly against the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc) are potential biomarkers and mechanistic contributors to cancer and other diseases associated with chronic inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22390546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Human heterophile antibodies that agglutinate animal erythrocytes are known to detect the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18669916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Nonhuman sialic acid Neu5Gc is very low in human embryonic stem cell-derived neural precursors differentiated with B27/N2 and noggin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16806174", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "A concern recently has been raised that human embryonic stem cell (HESC) lines cultured with currently available methods may have limited clinical usefulness due to the immunogenicity of the nonhuman sialic acid Neu5Gc incorporated into their membranes during culturing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16806174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Humans are genetically defective in synthesizing the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc), but can metabolically incorporate it from dietary sources (particularly red meat and milk) into glycoproteins and glycolipids of human tumors, fetuses and some normal tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "Humans are genetically defective in synthesizing the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc), but can metabolically incorporate it from dietary sources (particularly red meat and milk) into glycoproteins and glycolipids of human tumors, fetuses and some normal tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156207", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 335, "text": "Human cells cannot synthesize Neu5Gc due to dysfunction of the CMP-Neu5Ac hydroxylase (CMAH) gene, which converts CMP-Neu5Ac to CMP-Neu5Gc. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24829344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Humans are genetically incapable of producing the mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc), due to an inactivating mutation in the enzyme synthesizing it. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15972653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Humans are genetically defective in synthesizing the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": " Mammals express the sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). Neu5Gc is synthesized from Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25517696", "endSection": "abstract" }, { "offsetInBeginSection": 2241, "offsetInEndSection": 2431, "text": "Human cells cannot synthesize Neu5Gc because of dysfunction of the CMP-N-acetylneuraminic acid hydroxylase gene but can exogenously and metabolically incorporate Neu5Gc from dietary sources.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24829344", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 648, "text": "Finally, we demonstrate that the synthesized Neu5Gc can be incorporated into the cell glycocalyx of human cells, which do not naturally synthesize this sugar.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20452577", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 655, "text": "Here we show that SubB has a strong preference for glycans terminating in the sialic acid N-glycolylneuraminic acid (Neu5Gc), a monosaccharide not synthesized in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18971931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Humans are genetically incapable of producing the mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc), due to an inactivating mutation in the enzyme synthesizing it.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15972653", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by Orteronel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25533464", "http://www.ncbi.nlm.nih.gov/pubmed/24759590", "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "http://www.ncbi.nlm.nih.gov/pubmed/23856460", "http://www.ncbi.nlm.nih.gov/pubmed/24965748", "http://www.ncbi.nlm.nih.gov/pubmed/25537627", "http://www.ncbi.nlm.nih.gov/pubmed/24314737", "http://www.ncbi.nlm.nih.gov/pubmed/25264242", "http://www.ncbi.nlm.nih.gov/pubmed/21978946", "http://www.ncbi.nlm.nih.gov/pubmed/24844235", "http://www.ncbi.nlm.nih.gov/pubmed/23146910", "http://www.ncbi.nlm.nih.gov/pubmed/25297456", "http://www.ncbi.nlm.nih.gov/pubmed/23788266", "http://www.ncbi.nlm.nih.gov/pubmed/23880851", "http://www.ncbi.nlm.nih.gov/pubmed/24276076", "http://www.ncbi.nlm.nih.gov/pubmed/24418642", "http://www.ncbi.nlm.nih.gov/pubmed/23371447", "http://www.ncbi.nlm.nih.gov/pubmed/22249003" ], "ideal_answer": [ "Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. Orteronel is used for treatment for castration-resistant prostate cancer." ], "exact_answer": [ "CYP17A1" ], "type": "factoid", "id": "54e0c3e71388e8454a000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "PURPOSE: Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25537627", "endSection": "abstract" }, { "offsetInBeginSection": 883, "offsetInEndSection": 984, "text": "The drug orteronel selectively blocked the lyase reaction of P450 17A1 but only in the case of Prog. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Preclinical assessment of Orteronel(\u00ae), a CYP17A1 enzyme inhibitor in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25297456", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Orteronel (TAK-700) is a novel and selective inhibitor of CYP17A1, which is expressed in testicular, adrenal and prostate tumor tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25297456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25264242", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 480, "text": "Human liver microsomal studies indicated that orteronel weakly inhibits CYP1A2, 2C8, 2C9 and 2C19, with IC50 values of 17.8, 27.7, 30.8 and 38.8 \u00b5m, respectively, whereas orteronel does not inhibit CYP2B6, 2D6 or 3A4/5 (IC50 \u2009>\u2009100 \u00b5m).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25264242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "PURPOSE: Orteronel (TAK-700) is an investigational, nonsteroidal, oral, inhibitor of androgen synthesis with greater specificity for 17,20-lyase than for 17\u03b1-hydroxylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24965748", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 705, "text": "Based on these observations, potent agents targeting the AR axis were developed: 1) inhibitors of CYP17 (a key enzyme in the production of androgens), such as abiraterone and orteronel; 2) AR antagonists that bind to AR and impair AR activation, such as enzalutamide and ARN-509. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24844235", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 295, "text": "Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1309, "text": "Inhibition of 17\u03b1-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone (ACTH), providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-lyase (orteronel, galeterone and VT-464) that can potentially be administered without exogenous corticosteroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24759590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Phase I/II trial of orteronel (TAK-700)--an investigational 17,20-lyase inhibitor--in patients with metastatic castration-resistant prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24418642", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 319, "text": "Orteronel (TAK-700) is an investigational, oral, nonsteroidal, selective, reversible inhibitor of 17,20-lyase, a key enzyme in the production of androgenic hormones. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24418642", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 833, "text": "Hence, some molecules target the androgen biosynthesis, as abiraterone acetate and orteronel, which are selective inhibitors of the enzyme CYP17.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24314737", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1667, "text": "To achieve enhanced clinical benefits, new strategies are being explored that include selective inhibition of the C17,20-lyase activity of CYP17 and multi-targeting strategies that affect androgen synthesis and signalling at different points. Some of these strategies-including the drugs orteronel, VT-464 and galeterone--are supported by preclinical data and are being explored in the clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276076", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 943, "text": "Besides further CYP17 inhibitors (Orteronel, Galeterone, VT-464 and CFG920), androgen receptor antagonists (ARN-509, ODM-201, AZD-3514 and EZN-4176) and vaccine Prostvac, more drug candidates with various mechanisms or new indications of launched drugs are currently under evaluation in different stages of clinical trials, including various kinase inhibitors and platinum complexes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Effect of an investigational CYP17A1 inhibitor, orteronel (TAK-700), on estrogen- and corticoid-synthesis pathways in hypophysectomized female rats and on the serum estradiol levels in female cynomolgus monkeys.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23856460", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Orteronel (TAK-700) is an investigational, non-steroidal inhibitor of CYP17A1 with preferential inhibition of 17,20-lyase in NCI-H295 cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23856460", "endSection": "abstract" }, { "offsetInBeginSection": 1896, "offsetInEndSection": 2171, "text": "In summary, orteronel can suppress serum estradiol concentrations in hypophysectomized female rats and monkeys through selective inhibition of CYP17A1 activity, suggesting that orteronel might be effective for hormone-dependent breast cancers and estrogen-dependent diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23856460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Development and validation of an RP-HPLC method for the quantitation of Orteronel (TAK-700), a CYP17A1 enzyme inhibitor, in rat plasma and its application to a pharmacokinetic study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788266", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Targeting the adrenal gland in castration-resistant prostate cancer: a case for orteronel, a selective CYP-17 17,20-lyase inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371447", "endSection": "title" }, { "offsetInBeginSection": 769, "offsetInEndSection": 966, "text": "A new CYP17 inhibitor, with more selective inhibition of 17,20-lyase over 17\u03b1-hydroxylase, orteronel (TAK-700), is currently undergoing phase III clinical trials in pre- and postchemotherapy CRPC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Effect of a novel 17,20-lyase inhibitor, orteronel (TAK-700), on androgen synthesis in male rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146910", "endSection": "title" }, { "offsetInBeginSection": 181, "offsetInEndSection": 472, "text": "Orteronel (TAK-700), 6-[(7S)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthamide, is a novel, non-steroidal, selective inhibitor of the 17,20-lyase activity of CYP17A--a key enzyme in the production of steroidal hormones--and is being developed as a therapy for PC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146910", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 890, "text": "Orteronel inhibited 17,20-lyase activity in rats with an IC(50) of 1200 nM but did not inhibit 17\u03b1-hydroxylase or 11\u03b2-hydroxylase (CYP11B1) activity in rats at concentrations up to 10 \u03bcM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "title" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1532, "text": "Orteronel (TAK-700), a novel, selective, and potent inhibitor of 17,20-lyase is under development as a drug to inhibit androgen synthesis. In this study, we quantified the inhibitory activity and specificity of orteronel for testicular and adrenal androgen production by evaluating its effects on CYP17A1 enzymatic activity, steroid production in monkey adrenal cells and human adrenal tumor cells, and serum levels of dehydroepiandrosterone (DHEA), cortisol, and testosterone after oral dosing in castrated and intact male cynomolgus monkeys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "abstract" }, { "offsetInBeginSection": 2589, "offsetInEndSection": 2738, "text": " In summary, orteronel potently inhibited the 17,20-lyase activity of monkey and human CYP17A1 and reduced serum androgen levels in vivo in monkeys. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21978946", "endSection": "title" }, { "offsetInBeginSection": 181, "offsetInEndSection": 702, "text": "Orteronel (TAK-700), 6-[(7S)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthamide, is a novel, non-steroidal, selective inhibitor of the 17,20-lyase activity of CYP17A--a key enzyme in the production of steroidal hormones--and is being developed as a therapy for PC. The purpose of this study was to elucidate the inhibitory activity of orteronel, in particular its specificity for androgen synthesis enzymes, in male rats--an androgen-synthesis model that largely reflects this pathway in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146910", "endSection": "abstract" }, { "offsetInBeginSection": 2195, "offsetInEndSection": 2587, "text": "In terms of human CYP17A1 and human adrenal tumor cells, orteronel inhibited 17,20-lyase activity 5.4 times more potently than 17-hydroxylase activity in cell-free enzyme assays and DHEA production 27 times more potently than cortisol production in human adrenal tumor cells, suggesting greater specificity of inhibition between 17,20-lyase and 17-hydroxylase activities in humans vs monkeys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "abstract" }, { "offsetInBeginSection": 2588, "offsetInEndSection": 2735, "text": "In summary, orteronel potently inhibited the 17,20-lyase activity of monkey and human CYP17A1 and reduced serum androgen levels in vivo in monkeys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Orteronel (TAK-700) is a novel and selective inhibitor of CYP17A1, which is expressed in testicular, adrenal and prostate tumor tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25297456", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 292, "text": "Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1125, "text": "Orteronel (TAK-700), a novel, selective, and potent inhibitor of 17,20-lyase is under development as a drug to inhibit androgen synthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "abstract" }, { "offsetInBeginSection": 2590, "offsetInEndSection": 2736, "text": "In summary, orteronel potently inhibited the 17,20-lyase activity of monkey and human CYP17A1 and reduced serum androgen levels in vivo in monkeys", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 889, "text": "Orteronel inhibited 17,20-lyase activity in rats with an IC(50) of 1200 nM but did not inhibit 17\u03b1-hydroxylase or 11\u03b2-hydroxylase (CYP11B1) activity in rats at concentrations up to 10 \u03bcM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146910", "endSection": "abstract" }, { "offsetInBeginSection": 2197, "offsetInEndSection": 2588, "text": "In terms of human CYP17A1 and human adrenal tumor cells, orteronel inhibited 17,20-lyase activity 5.4 times more potently than 17-hydroxylase activity in cell-free enzyme assays and DHEA production 27 times more potently than cortisol production in human adrenal tumor cells, suggesting greater specificity of inhibition between 17,20-lyase and 17-hydroxylase activities in humans vs monkeys", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249003", "endSection": "abstract" }, { "offsetInBeginSection": 1896, "offsetInEndSection": 2170, "text": "In summary, orteronel can suppress serum estradiol concentrations in hypophysectomized female rats and monkeys through selective inhibition of CYP17A1 activity, suggesting that orteronel might be effective for hormone-dependent breast cancers and estrogen-dependent diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23856460", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 788, "text": "Hence, some molecules target the androgen biosynthesis, as abiraterone acetate and orteronel, which are selective inhibitors of the enzyme CYP17", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24314737", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 309, "text": "Orteronel (TAK-700) is an investigational, oral, nonsteroidal, selective, reversible inhibitor of 17,20-lyase, a key enzyme in the production of androgenic hormones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24418642", "endSection": "abstract" } ] }, { "body": "What is the disorder in which mutations in U4atac snRNA are detected?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21815888", "http://www.ncbi.nlm.nih.gov/pubmed/24865609", "http://www.ncbi.nlm.nih.gov/pubmed/21990275", "http://www.ncbi.nlm.nih.gov/pubmed/21474760", "http://www.ncbi.nlm.nih.gov/pubmed/21474761" ], "ideal_answer": [ "Mutations in U4atac snRNA are thought to be the cause of Microcephalic Osteodysplastic Primordial Dwarfism type I (MOPDI), a recessive form of developmental disorder.", "Biallelic mutations of the human RNU4ATAC gene, which codes for the minor spliceosomal U4atac snRNA, cause the developmental disorder, MOPD I/TALS " ], "exact_answer": [ "Microcephalic osteodysplastic primordial dwarfism type I (MOPDI)" ], "type": "factoid", "id": "54db5e24bcba1b1817000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Biallelic mutations of the human RNU4ATAC gene, which codes for the minor spliceosomal U4atac snRNA, cause the developmental disorder, MOPD I/TALS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865609", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 233, "text": "To date, nine separate mutations in RNU4ATAC have been identified in MOPD I patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865609", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1306, "text": "In this report, we establish a mechanistic basis for MOPD I disease and show that the inefficient splicing of genes containing U12-dependent introns in patient cells is due to defects in minor tri-snRNP formation, and the MOPD I-associated RNU4ATAC mutations can affect multiple facets of minor snRNA function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21990275", "endSection": "title" }, { "offsetInBeginSection": 307, "offsetInEndSection": 690, "text": "We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21990275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Microcephalic osteodysplastic primordial dwarfism type I with biallelic mutations in the RNU4ATAC gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815888", "endSection": "title" }, { "offsetInBeginSection": 338, "offsetInEndSection": 502, "text": "Recently, mutations in the RNU4ATAC gene, which encodes U4atac, a small nuclear RNA that is a crucial component of the minor spliceosome, were found to cause MOPD I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815888", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 761, "text": "We describe here the clinical and molecular data for 17 cases of MOPD I, including 15 previously unreported cases, all carrying biallelic mutations in the RNU4ATAC gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474760", "endSection": "title" }, { "offsetInBeginSection": 77, "offsetInEndSection": 446, "text": "By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474760", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 799, "text": "The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474761", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 571, "text": "We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with brain and bone malformations and unexplained postnatal death [microcephalic osteodysplastic primordial dwarfism type 1 (MOPD 1) or Taybi-Linder syndrome (TALS); Mendelian Inheritance in Man ID no. 210710].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Biallelic mutations of the human RNU4ATAC gene, which codes for the minor spliceosomal U4atac snRNA, cause the developmental disorder, MOPD I/TALS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865609", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 560, "text": "We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with brain and bone malformations and unexplained postnatal death [microcephalic osteodysplastic primordial dwarfism type 1 (MOPD 1) or Taybi-Linder syndrome (TALS); Mendelian Inheritance in Man ID no", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474761", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 501, "text": "Recently, mutations in the RNU4ATAC gene, which encodes U4atac, a small nuclear RNA that is a crucial component of the minor spliceosome, were found to cause MOPD I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815888", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 231, "text": "To date, nine separate mutations in RNU4ATAC have been identified in MOPD I patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865609", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1322, "text": "In this report, we establish a mechanistic basis for MOPD I disease and show that the inefficient splicing of genes containing U12-dependent introns in patient cells is due to defects in minor tri-snRNP formation, and the MOPD I-associated RNU4ATAC mutations can affect multiple facets of minor snRNA function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865609", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 589, "text": "MOPD I is the first disease known to be associated with a defect in small nuclear RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815888", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 445, "text": "By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474760", "endSection": "abstract" } ] }, { "body": "Which is the binding site motif of Sp1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10777687", "http://www.ncbi.nlm.nih.gov/pubmed/8063775", "http://www.ncbi.nlm.nih.gov/pubmed/8702907", "http://www.ncbi.nlm.nih.gov/pubmed/9261349", "http://www.ncbi.nlm.nih.gov/pubmed/12684058", "http://www.ncbi.nlm.nih.gov/pubmed/22021377" ], "ideal_answer": [ "Sp1 binds to a GC-rich sequence element containing the decanucleotide consensus sequence 5\u2032-(G/T)GGGCGG(G/A)(G/A)(C/T)-3\u2032 (GC box element) in double stranded DNA (dsDNA). Gel shift competition studies and DNase I footprinting analyses revealed that Sp1 specifically interacts with the CACCC motif." ], "exact_answer": [ "(G/T)GGGCGG(G/A)(G/A)(C/T)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016329" ], "type": "factoid", "id": "515d692c298dcd4e5100000a", "snippets": [ { "offsetInBeginSection": 609, "offsetInEndSection": 645, "text": "a GC-rich element (Sp1-binding site)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12684058", "endSection": "sections.0" }, { "offsetInBeginSection": 658, "offsetInEndSection": 743, "text": "Further analysis revealed that the DNA sequence, TTCAAGTCCCGCCCTCCGCT from -65 to -46", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10777687", "endSection": "sections.0" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1315, "text": "Sp1 motif in the UCR", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9261349", "endSection": "sections.0" }, { "offsetInBeginSection": 327, "offsetInEndSection": 445, "text": "upstream control region (UCR) containing a GC-rich motif (5'-GGGCGGG-3') and to a unique enhancer core (5'-TGCGGTC-3')", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9261349", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "A GC-rich region containing Sp1 and Sp1-like binding sites", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8702907", "endSection": "title" }, { "offsetInBeginSection": 699, "offsetInEndSection": 824, "text": "Gel shift competition studies and DNase I footprinting analyses revealed that Sp1 specifically interacts with the CACCC motif", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8063775", "endSection": "sections.0" }, { "offsetInBeginSection": 440, "offsetInEndSection": 629, "text": "In an effort to identify transcription factors that bind to the CACCC element, we found that purified human Sp1, as well as Sp1 in HeLa nuclear extract, can specifically bind to a DNA probe", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8063775", "endSection": "sections.0" }, { "offsetInBeginSection": 75, "offsetInEndSection": 116, "text": "Sp1 binds through an inverted CACCC motif", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8063775", "endSection": "title" } ] }, { "body": "List autoimmune disorders associated with GAD65 autoantibodies.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25566057", "http://www.ncbi.nlm.nih.gov/pubmed/12691864", "http://www.ncbi.nlm.nih.gov/pubmed/8816973", "http://www.ncbi.nlm.nih.gov/pubmed/25870548", "http://www.ncbi.nlm.nih.gov/pubmed/9451598", "http://www.ncbi.nlm.nih.gov/pubmed/14679108" ], "ideal_answer": [ "Autoantibodies to the smaller isoform of glutamate decarboxylase (GAD) can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis." ], "exact_answer": [ [ "type 1 diabetes" ], [ "stiff-person syndrome" ], [ "cerebellar ataxia" ], [ "limbic encephalitis" ] ], "type": "list", "id": "56f8077a8b98c98849000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Evidence for somatic mutation and affinity maturation of diabetes associated human autoantibodies to glutamate decarboxylase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8816973", "endSection": "title" }, { "offsetInBeginSection": 360, "offsetInEndSection": 516, "text": "The circulating autoantibodies to multiple islet autoantigens including GAD, insulin, and IA-2 are the important immunological features of type 1 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14679108", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 743, "text": "100% (39/39) selected type 1 diabetes mellitus (DM) patients,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12691864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Autoantibodies to the GM2-1 islet ganglioside and to GAD-65 at type 1 diabetes onset.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9451598", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Autoantibodies to the smaller isoform of glutamate decarboxylase (GAD) can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25870548", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 236, "text": " Anti-glutamic acid decarboxylase antibody (GAD-ab)-associated cerebellar ataxia is a rare neurological disorder characterized by cerebellar symptoms concomitant with high GAD-ab levels in serum and cerebrospinal fluid (CSF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25566057", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1398, "text": "The unique association of autoantibody-mediated cerebellar ataxia and late-onset T1DM in 2 siblings with similar clinical and paraclinical phenotypes strengthens the concept that hereditary factors might play a relevant role also in autoimmune diseases so far considered to be sporadic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25566057", "endSection": "abstract" } ] }, { "body": "Elaborate on the TREAT-NMD initiative for DMD patients", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "http://www.ncbi.nlm.nih.gov/pubmed/24148153", "http://www.ncbi.nlm.nih.gov/pubmed/23913485", "http://www.ncbi.nlm.nih.gov/pubmed/22068481" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0098343", "o": "D010361" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0098257", "o": "D010361" } ], "ideal_answer": [ "TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients in Europe. TREAT-NMD has worked on the generation of brief standards of care for DMD. Guidelines are presented for diagnostics, neurological follow up, gastrointestinal and nutritional issues, respiratory and cardiac care as well as orthopaedics, rehabilitation, psychosocial interventions and oral care." ], "concepts": [ "http://www.uniprot.org/uniprot/DMD_CANLF", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010361", "http://www.uniprot.org/uniprot/DMD_RAT", "http://www.uniprot.org/uniprot/DMD_HUMAN", "http://www.uniprot.org/uniprot/DMD_CHICK", "http://www.uniprot.org/uniprot/DMD_PIG" ], "type": "summary", "id": "56acd7530a360a5e45000004", "snippets": [ { "offsetInBeginSection": 524, "offsetInEndSection": 680, "text": "TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913485", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "The TREAT-NMD care and trial site registry: an online registry to facilitate clinical research for neuromuscular diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148153", "endSection": "title" }, { "offsetInBeginSection": 552, "offsetInEndSection": 762, "text": "TREAT-NMD Care and Trial Site Registry (CTSR), an initiative of an EU-funded Network of Excellence, and its utility in providing an infrastructure for clinical trial feasibility, recruitment, and other studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148153", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 970, "text": "A worldwide effort is underway to generate care guidelines for DMD, which involves the Centre for Disease Control in the USA and the TREAT-NMD network of excellence for neuromuscular diseases in Europe. In advance of the full consensus document, TREAT-NMD has worked on the generation of brief standards of care for DMD, which are presented here and are available via the TREAT-NMD website (http://www.treat-nmd.eu). Guidelines are presented for diagnostics, neurological follow up, gastrointestinal and nutritional issues, respiratory and cardiac care as well as orthopaedics, rehabilitation, psychosocial interventions and oral care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 960, "text": "In advance of the full consensus document, TREAT-NMD has worked on the generation of brief standards of care for DMD, which are presented here and are available via the TREAT-NMD website (http://www.treat-nmd.eu).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 832, "text": "TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913485", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 682, "text": "TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913485", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 715, "text": "In Europe, TREAT-NMD, a clinical research network for neuromuscular disorders, developeda global database for dystrophinopathy patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068481", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 764, "text": "METHODS: This paper describes the development of the TREAT-NMD Care and Trial Site Registry (CTSR), an initiative of an EU-funded Network of Excellence, and its utility in providing an infrastructure for clinical trial feasibility, recruitment, and other studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148153", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 752, "text": "In advance of the full consensus document, TREAT-NMD has worked on the generation of brief standards of care for DMD, which are presented here and are available via the TREAT-NMD website (http://www.treat-nmd.eu). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 744, "text": "This paper describes the development of the TREAT-NMD Care and Trial Site Registry (CTSR), an initiative of an EU-funded Network of Excellence, and its utility in providing an infrastructure for clinical trial feasibility, recruitment, and other studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148153", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 812, "text": "In Europe, TREAT-NMD, a clinical research network for neuromuscular disorders, developeda global database for dystrophinopathy patients. We developed a national registry of Japanese DMD/BMD patients in collaboration with TREAT-NMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068481", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 1073, "text": "The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913485", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 748, "text": "In advance of the full consensus document, TREAT-NMD has worked on the generation of brief standards of care for DMD, which are presented here and are available via the TREAT-NMD website (http://www.treat-nmd.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 738, "text": "A worldwide effort is underway to generate care guidelines for DMD, which involves the Centre for Disease Control in the USA and the TREAT-NMD network of excellence for neuromuscular diseases in Europe. In advance of the full consensus document, TREAT-NMD has worked on the generation of brief standards of care for DMD, which are presented here and are available via the TREAT-NMD website (http://www.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 813, "text": "TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913485", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 752, "text": "A worldwide effort is underway to generate care guidelines for DMD, which involves the Centre for Disease Control in the USA and the TREAT-NMD network of excellence for neuromuscular diseases in Europe. In advance of the full consensus document, TREAT-NMD has worked on the generation of brief standards of care for DMD, which are presented here and are available via the TREAT-NMD website (http://www.treat-nmd.eu).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 971, "text": "In advance of the full consensus document, TREAT-NMD has worked on the generation of brief standards of care for DMD, which are presented here and are available via the TREAT-NMD website (http://www.treat-nmd.eu). Guidelines are presented for diagnostics, neurological follow up, gastrointestinal and nutritional issues, respiratory and cardiac care as well as orthopaedics, rehabilitation, psychosocial interventions and oral care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20225016", "endSection": "abstract" } ] }, { "body": "Is muscle regeneration possible in mdx mice with the use of induced mesenchymal stem cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17999592", "http://www.ncbi.nlm.nih.gov/pubmed/25102299" ], "ideal_answer": [ "Purified induced mesenchymal stem cells (iMSCs) display fibroblast-like morphology, form three-dimensional spheroid structures, express characteristic mesenchymal stem cell surface markers such as CD29, CD33, CD73, CD90, and CD105, and are capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplantation of iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowers oxidative damage, and restores the expression levels of normal dystrophin, leading to skeletal muscle regeneration.", "Purified iMSCs displayed fibroblast-like morphology, formed three-dimensional spheroid structures, and expressed characteristic mesenchymal stem cell surface markers such as CD29, CD33, CD73, CD90, and CD105. Moreover, iMSCs were capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplanting iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowered oxidative damage as evidenced by a reduction in nitrotyrosine levels, and normal dystrophin expression levels were restored" ], "exact_answer": "yes", "type": "yesno", "id": "57134d511174fb1755000002", "snippets": [ { "offsetInBeginSection": 622, "offsetInEndSection": 1147, "text": "Purified iMSCs displayed fibroblast-like morphology, formed three-dimensional spheroid structures, and expressed characteristic mesenchymal stem cell surface markers such as CD29, CD33, CD73, CD90, and CD105. Moreover, iMSCs were capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplanting iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowered oxidative damage as evidenced by a reduction in nitrotyrosine levels, and normal dystrophin expression levels were restored", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102299", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1260, "text": "This study demonstrates the therapeutic potential of purified iMSCs in skeletal muscle regeneration in mdx mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Flk-1+ adipose-derived mesenchymal stem cells differentiate into skeletal muscle satellite cells and ameliorate muscular dystrophy in mdx mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17999592", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 784, "text": "Within mdx mice, an animal model of DMD, adipose tissue-derived Flk-1(+) MSCs (AD-MSCs) homed to and differentiated into cells that repaired injured muscle tissue. This repair correlated with reconstitution of dystrophin expression on the damaged fibers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17999592", "endSection": "abstract" }, { "offsetInBeginSection": 1076, "offsetInEndSection": 1133, "text": "Flk-1(+) AD-MSC transplants may repair muscular dystrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17999592", "endSection": "abstract" }, { "offsetInBeginSection": 1336, "offsetInEndSection": 1531, "text": "This study demonstrates the therapeutic potential of purified iMSCs in skeletal muscle regeneration in mdx mice, and suggests that iPSCs are a viable alternate source for deriving MSCs as needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102299", "endSection": "abstract" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1147, "text": "Transplanting iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowered oxidative damage as evidenced by a reduction in nitrotyrosine levels, and normal dystrophin expression levels were restored", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102299", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1343, "text": "This study demonstrates the therapeutic potential of purified iMSCs in skeletal muscle regeneration in mdx mice, and suggests that iPSCs are a viable alternate source for deriving MSCs as needed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102299", "endSection": "abstract" } ] }, { "body": "List the different subtypes of thyroid cancer.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17985985", "http://www.ncbi.nlm.nih.gov/pubmed/20969692", "http://www.ncbi.nlm.nih.gov/pubmed/21169742", "http://www.ncbi.nlm.nih.gov/pubmed/21553140", "http://www.ncbi.nlm.nih.gov/pubmed/8608779", "http://www.ncbi.nlm.nih.gov/pubmed/21272686", "http://www.ncbi.nlm.nih.gov/pubmed/24163390" ], "ideal_answer": [ "The different histologic subtypes of thyroid cancer include papillary, follicular, anaplastic, medullary, and H\u00fcrthle cell carcinomas." ], "exact_answer": [ [ "Papillary thyroid carcinoma" ], [ "Follicular thyroid carcinoma" ], [ "Anaplastic thyroid carcinoma" ], [ "Medullary thyroid carcinoma" ], [ "H\u00fcrthle cell carcinoma" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1781" ], "type": "list", "id": "5503145ee9bde69634000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 458, "text": "Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, the treatment of radio-resistant papillary-type, of undifferentiated anaplastic, and of medullary-type thyroid cancers remains unsatisfactory", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163390", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1090, "text": "Supervised hierarchical cluster analysis demonstrated grouping of 2 histologies (papillary and follicular thyroid carcinoma)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21553140", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 1199, "text": "FDG-PET/CT is also useful in the initial (post thyroidectomy) staging of high-risk patients with less differentiated (and thus less iodine-avid and clinically more aggressive) subtypes, such as tall cell variant and H\u00fcrthle cell carcinoma, but in particular poorly differentiated and anaplastic carcinoma. FDG-PET/CT may help in defining the extent of disease in some patients with medullary thyroid carcinoma and rising postoperative calcitonin levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21272686", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 399, "text": "Histologic subtypes included papillary (41%), follicular (22%), anaplastic (19%), medullary (15%), and H\u00fcrthle cell carcinomas (4%)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17985985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Follicular thyroid cancer is the second most common thyroid malignancy after PTC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8608779", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1307, "text": "Thyroid cancer subtypes were 90 patients with papillary thyroid cancer PTC, 24 with follicular FTC, eight with medullary MTC and two with anaplastic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20969692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Papillary thyroid carcinoma is the most common type of thyroid malignancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169742", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 1027, "text": "The main objectives of this review article are to (1) summarize the gross and histopathologic features of papillary thyroid carcinoma; (2) provide an overview of the subtypes of papillary thyroid carcinoma and their prognosis; (3) discuss established and emerging data on the immunohistochemical findings that are helpful in differential diagnosis; and (4) summarize molecular findings and pathogenesis of these lesions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169742", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 413, "text": "Although the vast majority of papillary thyroid carcinomas have an excellent prognosis, some variants of papillary thyroid carcinoma can have a more aggressive course", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169742", "endSection": "abstract" } ] }, { "body": "What are the characteristics of Christianson syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "http://www.ncbi.nlm.nih.gov/pubmed/18342287", "http://www.ncbi.nlm.nih.gov/pubmed/24035762", "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "http://www.ncbi.nlm.nih.gov/pubmed/25273398", "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "http://www.ncbi.nlm.nih.gov/pubmed/24839169", "http://www.ncbi.nlm.nih.gov/pubmed/24285247", "http://www.ncbi.nlm.nih.gov/pubmed/24779060", "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "http://www.ncbi.nlm.nih.gov/pubmed/22541666" ], "ideal_answer": [ "Christianson syndrome (CS) is caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). Patients present with prominent neurological, medical, and behavioral symptoms. All CS participants were nonverbal and had intellectual disability, epilepsy, and ataxia. Other neurologic symptoms included eye movement abnormalities (79%), postnatal microcephaly (92%), and magnetic resonance imaging evidence of cerebellar atrophy (33%). Regression was noted in 50%, with recurrent presentations involving loss of words and/or the ability to walk. Medical symptoms, particularly gastrointestinal symptoms, are common. Height and body mass index measures were below normal ranges in most participants. Behavioral symptoms included hyperkinetic behavior (100%), and a majority exhibited high pain threshold." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020969", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004827", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001259" ], "type": "summary", "id": "571e469bbb137a4b0c00000d", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 142, "text": "Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1590, "text": "We also report prominent neurological, medical, and behavioral symptoms. All CS participants were nonverbal and had intellectual disability, epilepsy, and ataxia. Many had prior diagnoses of autism and/or Angelman syndrome. Other neurologic symptoms included eye movement abnormalities (79%), postnatal microcephaly (92%), and magnetic resonance imaging evidence of cerebellar atrophy (33%). Regression was noted in 50%, with recurrent presentations involving loss of words and/or the ability to walk. Medical symptoms, particularly gastrointestinal symptoms, were common. Height and body mass index measures were below normal ranges in most participants. Behavioral symptoms included hyperkinetic behavior (100%), and a majority exhibited high pain threshold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1147, "text": "The single-gene disorders include Pitt\u2013Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat\u2013Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779060", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 804, "text": "Among these are classic disorders such as Angelman syndrome and MECP2-related disorder (formerly Rett syndrome), as well as more recently described clinical entities associated with mutations in CASK, CDKL5, CREBBP, and EP300 (Rubinstein-Taybi syndrome), FOXG1, SLC9A6 (Christianson syndrome), and TCF4 (Pitt-Hopkins syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24839169", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 658, "text": "Mutations in SLC9A6 are associated with Christianson syndrome (OMIM 300243), a syndromic form of X-linked mental retardation (XLMR) characterized by microcephaly, severe global developmental delay, ataxia and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Mutations in the SLC9A6 gene cause Christianson syndrome in boys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Mutations in the SLC9A6 gene cause Christianson syndrome in boys. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 443, "text": "Mutations in SLC9A6 are associated with Christianson syndrome (OMIM 300243), a syndromic form of X-linked mental retardation (XLMR) characterized by microcephaly, severe global developmental delay, ataxia and seizures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1131, "text": "In contrast to the majority of reported Christianson syndrome patients who were microcephalic, this patient was normocephalic, but his head circumference had decelerated from the 50th centile at birth to the 25th centile at the age of 2 \u00b2/\u00b9\u00b2 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Novel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Mutations in the SLC9A6 gene cause Christianson syndrome in boys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Mutations in SLC9A6 are associated with Christianson syndrome (OMIM 300243), a syndromic form of X-linked mental retardation (XLMR) characterized by microcephaly, severe global developmental delay, ataxia and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18342287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "In contrast to the majority of reported Christianson syndrome patients who were microcephalic, this patient was normocephalic, but his head circumference had decelerated from the 50th centile at birth to the 25th centile at the age of 2 / years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Christianson syndrome (CS) is an X-linked neurodevelopmental disorder caused by deleterious mutations in SLC9A6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25273398", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 213, "text": "This X-linked syndrome is characterized by profound mental retardation with autistic behavior, microcephaly, epilepsy, ophthalmoplegia, and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 584, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia. In a 7-year-old boy with characteristic clinical and neuroimaging features of Christianson syndrome and epileptic encephalopathy with continuous spikes and waves during sleep, we identified a novel splice site mutation (IVS10-1G>A) in SLC9A6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 973, "text": "The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan\u2013McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single-gene disorders include Pitt\u2013Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat\u2013Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779060", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1112, "text": "The single-gene disorders include Pitt\u2013Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat\u2013Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": " Christianson syndrome (CS) is an X-linked neurodevelopmental disorder caused by deleterious mutations in SLC9A6. Affected families organized the inaugural Christianson Syndrome Association conference to advance CS knowledge and develop questions that may be prioritized in future research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25273398", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 479, "text": "Among these are classic disorders such as Angelman syndrome and MECP2-related disorder (formerly Rett syndrome), as well as more recently described clinical entities associated with mutations in CASK, CDKL5, CREBBP, and EP300 (Rubinstein-Taybi syndrome), FOXG1, SLC9A6 (Christianson syndrome), and TCF4 (Pitt-Hopkins syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24839169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 973, "text": "The single-gene disorders include Pitt\u2013Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat\u2013Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Mutations in the SLC9A6 gene cause Christianson syndrome in boys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Novel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "endSection": "abstract" } ] }, { "body": "Is the SDHAF2 gene encoding a protein necessary for flavination of SDHA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "http://www.ncbi.nlm.nih.gov/pubmed/23036115", "http://www.ncbi.nlm.nih.gov/pubmed/19732718", "http://www.ncbi.nlm.nih.gov/pubmed/23061808" ], "ideal_answer": [ "Yes, SDHAF2 or hSDH5, is the gene encoding the enzyme responsible for the flavination of SDHA.", "Yes, SDHAF2 is required for flavination of SDHA." ], "exact_answer": "yes", "type": "yesno", "id": "571e06447de986d80d000016", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 198, "text": "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 786, "text": "At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23061808", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 721, "text": "the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23061808", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 196, "text": "SDHAF2, required for flavination of SDHA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "endSection": "abstract" }, { "offsetInBeginSection": 784, "offsetInEndSection": 1189, "text": "At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23061808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 407, "text": "In a recent issue of Science, Rutter and coworkers showed that SDH5 is required for the flavination of SDHA, which is necessary for SDH assembly and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19732718", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 785, "text": "At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23061808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "CONTEXT: Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 647, "text": "This gene is co-expressed with a number of genes encoding mitochondrial proteins, including SDH1-1, and has low partial sequence similarity to human SDHAF2, a protein required for flavin-adenine dinucleotide (FAD) insertion into SDH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036115", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 787, "text": "At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23061808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "endSection": "abstract" } ] }, { "body": "What is the physiological role of LKB1 involved in Peutz-Jeghers syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20020146" ], "ideal_answer": [ "LKB1 plays a physiological role in controlling the Wnt-signaling." ], "exact_answer": [ "LKB1 plays a physiological role in controlling the Wnt-signaling." ], "concepts": [ "http://www.uniprot.org/uniprot/STK11_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010580", "http://www.disease-ontology.org/api/metadata/DOID:3852" ], "type": "factoid", "id": "53175e9fb166e2b80600000a", "snippets": [ { "offsetInBeginSection": 155, "offsetInEndSection": 423, "text": "Recent functional genetic studies have pointed out that LKB1 plays a physiological role in controlling the Wnt-signaling pathway and activation of the pathway as a consequence of LKB1 haploinsufficiency might be responsible for the development of harmatomatous polyps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20020146", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1078, "text": "PJS polyps from all patients showed generalized membrane and cytoplasmic localizations of beta-catenin along the mucosal endothelium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20020146", "endSection": "abstract" } ] }, { "body": "What heterotachy states about molecular evolutionary processes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19687305", "http://www.ncbi.nlm.nih.gov/pubmed/20724379", "http://www.ncbi.nlm.nih.gov/pubmed/19822637", "http://www.ncbi.nlm.nih.gov/pubmed/17366138", "http://www.ncbi.nlm.nih.gov/pubmed/12880207", "http://www.ncbi.nlm.nih.gov/pubmed/19482090", "http://www.ncbi.nlm.nih.gov/pubmed/16209710", "http://www.ncbi.nlm.nih.gov/pubmed/16014870", "http://www.ncbi.nlm.nih.gov/pubmed/18852097", "http://www.ncbi.nlm.nih.gov/pubmed/17974035", "http://www.ncbi.nlm.nih.gov/pubmed/16151191", "http://www.ncbi.nlm.nih.gov/pubmed/18319244", "http://www.ncbi.nlm.nih.gov/pubmed/21186190", "http://www.ncbi.nlm.nih.gov/pubmed/20045073", "http://www.ncbi.nlm.nih.gov/pubmed/11752184", "http://www.ncbi.nlm.nih.gov/pubmed/16672284", "http://www.ncbi.nlm.nih.gov/pubmed/17288568", "http://www.ncbi.nlm.nih.gov/pubmed/21235782", "http://www.ncbi.nlm.nih.gov/pubmed/15746012" ], "ideal_answer": [ "Functional constraints may account for heterogeneity in the evolutionary rates among different sites of amino acid or DNA sequences. Apart from variations of substitution rates among different sites (spatial variation), heterotachy states that there are variations of substitution rates of a given site throughout time. Heterotachy is the within-site evolutionary rate variations across different lineages over time. Heterotachy (temporal rate variation) occurs with varying severity because the intensity of purifying selection and adaptive forces acting at a given position of a homologous amino acid or DNA sequence are not the same in different species. Heterotachy may mislead phylogenetic inferences." ], "type": "summary", "id": "55479102f35db75526000004", "snippets": [ { "offsetInBeginSection": 223, "offsetInEndSection": 397, "text": "One of the properties of protein evolution is the variation of the relative rate of substitutions across sites and over time, the latter is the phenomenon called heterotachy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21235782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Heterotachy is a general term to describe positions that evolve at different rates in different lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21186190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "There is widespread evidence of lineage-specific rate variation, known as heterotachy, during protein evolution. Changes in the structural and functional constraints acting on a protein can lead to heterotachy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20724379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 538, "text": "Variation in substitution rates among evolutionary lineages (among-lineage rate variation or ALRV) has been reported to negatively affect the estimation of phylogenies. When the substitution processes underlying ALRV are modeled inadequately, non-sister taxa with similar substitution rates are estimated incorrectly as sister species due to long-branch attraction. Recent advances in modeling site-specific rate variation (heterotachy) have reduced the impacts of ALRV on phylogeny estimation in several empirical and simulated datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20045073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Heterotachy, the variation of substitution rate at a site across time, is a prevalent phenomenon in nucleotide and amino acid alignments, which may mislead probabilistic-based phylogenetic inferences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19822637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Heterotachy is a general term to describe positions in a sequence that evolve at different rates in different lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19687305", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 472, "text": "homotachy (i.e., the evolutionary rates within lineages in each of the concatenated genes are constant during evolution). Here, we examine how the violation of homotachy (i.e., presence of within-site rate variation, called heterotachy) distorts species phylogenies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19482090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "The rate at which a given site in a gene sequence alignment evolves over time may vary. This phenomenon--known as heterotachy--can bias or distort phylogenetic trees inferred from models of sequence evolution that assume rates of evolution are constant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18852097", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 260, "text": "The evolutionary rate at a given homologous position varies across time. When sufficiently pronounced, this phenomenon - called heterotachy - may produce artefactual phylogenetic reconstructions under the commonly used models of sequence evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17974035", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 842, "text": "Rate-across-site (RAS) models are commonly used evolutionary models in phylogenetic studies. These account for heterogeneity in the evolutionary rates among sites but do not account for changing within-site rates across lineages (heterotachy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17366138", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 304, "text": "The rate of evolution varies spatially along genomes and temporally in time. The presence of evolutionary rate variation is an informative signal that often marks functional regions of genomes and historical selection events. There exist many tests for temporal rate variation, or heterotachy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17288568", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 554, "text": "heterotachy, a phenomenon that corresponds to shifts in site-specific evolutionary rates over time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16209710", "endSection": "abstract" }, { "offsetInBeginSection": 1365, "offsetInEndSection": 1405, "text": "within-site rate variation (heterotachy)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16209710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 588, "text": "Because of functional constraints, substitution rates vary among the positions of a protein but are usually assumed to be constant at a given site during evolution. The distribution of the rates across the sequence positions generally fits a Gamma distribution. Models of sequence evolution were accordingly designed and led to improved phylogenetic reconstruction. However, it has been convincingly demonstrated that the evolutionary rate of a given position is not always constant throughout time. We called such within-site rate variations heterotachy (for \"different speed\" in Greek).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11752184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Heterotachy occurs when the relative evolutionary rates among sites are not the same across lineages. Sequence alignments are likely to exhibit heterotachy with varying severity because the intensity of purifying selection and adaptive forces at a given amino acid or DNA sequence position is unlikely to be the same in different species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16014870", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1212, "text": "compare the evolutionary properties of homologous sequence positions in paralogs. It has been proposed that the positions that show switches in substitution rate over time--i.e., 'heterotachous sites'--are good indicators of functional divergence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12880207", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 685, "text": "Many molecular sequences, however, exhibit site-specific changes in evolutionary rates, called \"heterotachy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18319244", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 837, "text": "These account for heterogeneity in the evolutionary rates among sites but do not account for changing within-site rates across lineages (heterotachy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17366138", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 540, "text": "However, recent work by Kolaczkowski and Thornton suggested, on the basis of simulations, that MP is less sensitive than ML to tree reconstruction artefacts generated by heterotachy, a phenomenon that corresponds to shifts in site-specific evolutionary rates over time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16209710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Evolutionary rates vary among sites and across the phylogenetic tree (heterotachy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15746012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The principle of heterotachy states that the substitution rate of sites in a gene can change through time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16672284", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 689, "text": "Many molecular sequences, however, exhibit site-specific changes in evolutionary rates, called \"heterotachy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18319244", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 1063, "text": "Many molecular sequences, however, exhibit site-specific changes in evolutionary rates, called \"heterotachy.\" Here we examine the accuracy of 2 phylogenetic methods for incorporating heterotachy, the mixed branch length model--which incorporates site-specific rate changes by summing likelihoods over multiple sets of branch lengths on the same tree--and the covarion model, which uses a hidden Markov process to allow sites to switch between variable and invariable as they evolve.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18319244", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 1062, "text": "Many molecular sequences, however, exhibit site-specific changes in evolutionary rates, called \"heterotachy.\" Here we examine the accuracy of 2 phylogenetic methods for incorporating heterotachy, the mixed branch length model--which incorporates site-specific rate changes by summing likelihoods over multiple sets of branch lengths on the same tree--and the covarion model, which uses a hidden Markov process to allow sites to switch between variable and invariable as they evolve", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18319244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The principle of heterotachy states that the substitution rate of sites in a gene can change through time", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16672284", "endSection": "abstract" } ] }, { "body": "What is known about depression in caregivers of brain tumor patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12605978", "http://www.ncbi.nlm.nih.gov/pubmed/23104453", "http://www.ncbi.nlm.nih.gov/pubmed/18481737", "http://www.ncbi.nlm.nih.gov/pubmed/21994513", "http://www.ncbi.nlm.nih.gov/pubmed/19159080", "http://www.ncbi.nlm.nih.gov/pubmed/23438646", "http://www.ncbi.nlm.nih.gov/pubmed/18061752", "http://www.ncbi.nlm.nih.gov/pubmed/24152975", "http://www.ncbi.nlm.nih.gov/pubmed/23615145", "http://www.ncbi.nlm.nih.gov/pubmed/23187335", "http://www.ncbi.nlm.nih.gov/pubmed/23989499", "http://www.ncbi.nlm.nih.gov/pubmed/23633116", "http://www.ncbi.nlm.nih.gov/pubmed/16532486", "http://www.ncbi.nlm.nih.gov/pubmed/23384776", "http://www.ncbi.nlm.nih.gov/pubmed/22585179", "http://www.ncbi.nlm.nih.gov/pubmed/22307475", "http://www.ncbi.nlm.nih.gov/pubmed/18329220", "http://www.ncbi.nlm.nih.gov/pubmed/21968946", "http://www.ncbi.nlm.nih.gov/pubmed/17760798" ], "ideal_answer": [ "Depression is common affecting up to 40% of caregivers of brain tumor patients. Depression is associated with poor quality of life of caregivers of brain tumor patients. Greater anxiety, patients\u2019 emotional distress, economic hardship, lower caregivers\u2019 age, lower income, less social support and lower patient functioning were associated with more caregivers\u2019 depressive symptoms. Reports of caregiver depressive symptoms were lower when paired with higher reports of spirituality. It is important to monitor and treat caregiver's depression." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932", "http://www.disease-ontology.org/api/metadata/DOID:1596", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003866", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003865", "http://www.disease-ontology.org/api/metadata/DOID:1470", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017028", "http://www.disease-ontology.org/api/metadata/DOID:1319" ], "type": "summary", "id": "530f72fd329f5fcf1e000003", "snippets": [ { "offsetInBeginSection": 714, "offsetInEndSection": 1063, "text": "Data suggest that patients with primary or metastatic brain tumours often have a high symptom burden and unmet needs for palliative care, and symptoms are hard to diagnose; patients suffer often and early from cognitive impairment but are rarely appropriately prepared concerning end-of-life wishes. This reflects on their caregivers' burden as well", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24152975", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1061, "text": "Reports of caregiver depressive symptoms and anxiety were lower when paired with higher reports of spirituality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23615145", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 618, "text": "Fifty-nine percent did not receive any financial aid for home care, 33% had increased risk for psychosomatic problems, 45% had anxiety, and 33% increased depression levels. The caregiver's quality of life was most strongly affected by the burden of care (p < .001) and the patient's mental state (p < .03).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23438646", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 94, "text": "Depressive symptoms are common in cancer patients and their family caregivers (FCs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23187335", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 246, "text": "The psychological burden induced by brain tumor is profound both for the sick person and for their own family. This particular tumor not only impacts patients' quality of life, but also reduces seriously the caregivers' quality of life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104453", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1061, "text": "Most caregivers experienced more depressive and anxiety symptoms, as compared with patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104453", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1525, "text": "Therefore, it is necessary to monitor and treat, if necessary, caregivers' anxious or depressive symptomatology that impacts their quality of life, making them more helpless, frustrated and less able to handle the situation of disease and caregiving situation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104453", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 1199, "text": "Group-based trajectory modeling identified high-decreasing (51.1 % of caregivers) and consistently low (48.9 %) depressive symptom trajectories, high-decreasing (75.5 %) and low-decreasing (24.5 %) anxiety trajectories, and high (37.5 %), moderate (40.9 %), and low-decreasing (21.6 %) caregiver burden trajectories. High depressive symptoms were associated with high trajectories for both anxiety and burden, lower caregivers age, income, and social support, and lower care recipient functioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22585179", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 977, "text": "Studies suggest rates of depression and anxiety up to 48% in patients and up to 40% in caregivers, with many unmet needs and dissatisfaction with health care provider communication and information. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22307475", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1091, "text": "Caregivers try to react to the illness of their relatives by mobilizing their physical reaction and growing their self-esteem, but they live with a clinically significant impairment of their quality of life, and experience a deep level of anxiety and depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21968946", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 857, "text": " There was a trend for economic hardship to predict CG depressive symptoms at 4 months (P = 0.09), but not at diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19159080", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 400, "text": "Although previous research has documented the stress, depression, anxiety, and burden associated with caregiving, when these conditions occur is not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18481737", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1116, "text": "Among patients, 30% reported anxious mood and 17% depressed mood on the HADS, while corresponding numbers for carers were 40% and 10%, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18329220", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 1163, "text": "Among patients and carers, 30% and 40%, respectively, reported anxious moods and 17% and 10%, respectively, reported depressed moods on the HADS. Significant correlations were observed between the FACT-G and HADS subscales, particularly emotional well-being and anxiety, as well as physical and functional well-being and depression, and between patients' and their carers' quality of life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18061752", "endSection": "abstract" }, { "offsetInBeginSection": 1382, "offsetInEndSection": 1548, "text": "Findings showed a link between care recipients' problem behaviors and caregivers' depressive symptoms, a relationship that has not been well established in oncology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17760798", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 578, "text": "Care recipients' neuropsychiatric status consistently affected caregivers' depressive symptoms and burden, and assisting with activities of daily living affected burden related to caregivers' schedules and health. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16532486", "endSection": "abstract" } ] }, { "body": "What are the effects of homozygosity of EDNRB mutations in addition to Hirschsprung disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16237557", "http://www.ncbi.nlm.nih.gov/pubmed/12939697", "http://www.ncbi.nlm.nih.gov/pubmed/11324313", "http://www.ncbi.nlm.nih.gov/pubmed/11891690", "http://www.ncbi.nlm.nih.gov/pubmed/9885824", "http://www.ncbi.nlm.nih.gov/pubmed/8852660" ], "ideal_answer": [ "Three susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene, the endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous EDNRB an EDN3 missense mutations have been reported in isolated HSCR patients ", "EDNRB homozygous mutations have been found to account for the rare Waardenburg-Hirschsprung syndrome (WS), whereas heterozygous EDNRB missense mutations have been reported in isolated Hirschsprung disease patients." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627", "http://www.disease-ontology.org/api/metadata/DOID:10487" ], "type": "summary", "id": "55391825bc4f83e828000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16237557", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 1143, "text": "The index patient, who was born to a family with no history of Hirschsprung disease, presented total colonic aganglionosis with small bowel extension, sensorineural hearing loss and generalized cutaneous pigmentary defects. Interestingly, both irides were normally black. The study detected a homozygous missense mutation at codon 196 in exon 2 (Ser196Asn), which has not been reported. Both parents and four in six siblings harbored heterozygous mutation without any clinical manifestation. Our findings were consistent with previous observations that full spectrum of WS4 occurred to the mutate homozygotes. Moreover, the non-penetrance of heterozygotes in our pedigree, which differs from other reports, demonstrates the high pleiotropic effect of EDNRB mutations in human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16237557", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 864, "text": "Our own studies could show that, whereas a homozygous mutation of EDNRB causes long-segment HSCR, a heterozygous EDNRB deficiency leads to alterations of the ENS resembling the histopathology observed in intestinal neuronal dysplasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12939697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 741, "text": "ABCD syndrome is an autosomal recessive syndrome characterized by albinism, black lock, cell migration disorder of the neurocytes of the gut (Hirschsprung disease [HSCR]), and deafness. This phenotype clearly overlaps with the features of the Shah-Waardenburg syndrome, comprising sensorineural deafness; hypopigmentation of skin, hair, and irides; and HSCR. Therefore, we screened DNA of the index patient of the ABCD syndrome family for mutations in the endothelin B receptor (EDNRB) gene, a gene known to be involved in Shah-Waardenburg syndrome. A homozygous nonsense mutation in exon 3 (R201X) of the EDNRB gene was found. We therefore suggest that ABCD syndrome is not a separate entity, but an expression of Shah-Waardenburg syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11891690", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 627, "text": "Three susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene, the endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous EDNRB an EDN3 missense mutations have been reported in isolated HSCR patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11324313", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 628, "text": "Three susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene, the endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous EDNRB and EDN3 missense mutations have been reported in isolated HSCR patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9885824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16237557", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 380, "text": "Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 725, "text": "These data might suggest that EDNRB mutations could be dosage sensitive: heterozygosity would predispose to isolated HSCR with incomplete penetrance, while homozygosity would result in more complex neurocristopathies associating HSCR and WS features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 519, "text": "RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11324313", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 519, "text": "RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9885824", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 382, "text": "Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16237557", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 381, "text": "Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 520, "text": "RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9885824", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 520, "text": "RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11324313", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 728, "text": "These data might suggest that EDNRB mutations could be dosage sensitive: heterozygosity would predispose to isolated HSCR with incomplete penetrance, while homozygosity would result in more complex neurocristopathies associating HSCR and WS features", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" } ] }, { "body": "What is the prognostic role of alterred thyroid profile after cardiosurgery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12475369", "http://www.ncbi.nlm.nih.gov/pubmed/14500064", "http://www.ncbi.nlm.nih.gov/pubmed/15868525", "http://www.ncbi.nlm.nih.gov/pubmed/21959513", "http://www.ncbi.nlm.nih.gov/pubmed/21097430", "http://www.ncbi.nlm.nih.gov/pubmed/19303793", "http://www.ncbi.nlm.nih.gov/pubmed/1929631", "http://www.ncbi.nlm.nih.gov/pubmed/16677263", "http://www.ncbi.nlm.nih.gov/pubmed/19463607" ], "ideal_answer": [ "Altered thyroid profile after cardiosurgery is associated with high incidence of atrial fibrillation e delay in recovery (prolonged hospitalisation) in adults and higher score on The Pediatric Risk of Mortality (PRISM; P < 0.042) and a longer duration of ventilation in children.Impportantly in transplanted patients altered thyroid metabolism,low T3 syndrome, is characterized by highest mortality, highest incidence of acute rejection or reoperations and infections" ], "exact_answer": [ "Altered thyroid profile after cardiosurgery is associated with several events in adults and in children" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010361", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013903", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013959", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379" ], "type": "factoid", "id": "53265dd4d6d3ac6a34000007", "snippets": [ { "offsetInBeginSection": 919, "offsetInEndSection": 1161, "text": " Patients with fT3 syndrome had the highest mortality (16.7%, NS), highest incidence of acute rejection (38.9%, NS), highest number of reoperations (27.8%, NS), and highest incidence of bacterial (16.7%, NS) and fungal infections (11.1%, NS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21959513", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1546, "text": "SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463607", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1338, "text": "There was a significant inverse relationship between fT3 levels and global oxygen consumption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19303793", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 869, "text": "However, in the high inotropic support group, FT4 was lower for a longer time. This group also had a significantly higher score on The Pediatric Risk of Mortality (PRISM; P < 0.042) and a longer duration of ventilation (P < 0.014). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16677263", "endSection": "abstract" }, { "offsetInBeginSection": 1878, "offsetInEndSection": 2059, "text": " In a group of elderly patients undergoing cardiac surgery, there was a strong association between a postoperative decrease of serum triiodothyronine levels and atrial fibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15868525", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1575, "text": "Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500064", "endSection": "abstract" }, { "offsetInBeginSection": 1359, "offsetInEndSection": 1488, "text": "Those with an uneventful recovery had a higher serum free T4 level on the sixth day after operation than those with complications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1929631", "endSection": "abstract" }, { "offsetInBeginSection": 1312, "offsetInEndSection": 1488, "text": "Enhancement of T3 levels after mitral valve replacement may increase the probability of early spontaneous cardioversion of AF, but can not affect the duration of sinus rhythm. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097430", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1294, "text": "A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12475369", "endSection": "abstract" } ] }, { "body": "List Pentalogy of Fallot.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24594084", "http://www.ncbi.nlm.nih.gov/pubmed/17283405", "http://www.ncbi.nlm.nih.gov/pubmed/22461877", "http://www.ncbi.nlm.nih.gov/pubmed/26393185", "http://www.ncbi.nlm.nih.gov/pubmed/11432800", "http://www.ncbi.nlm.nih.gov/pubmed/23758042" ], "ideal_answer": [ "Pentalogy of Fallot consists of a pulmonic stenosis, a ventricular septal defect, an overriding aorta, a right ventricular hypertrophy and a patent foramen ovale." ], "exact_answer": [ [ "pulmonic stenosis" ], [ "ventricular septal defect" ], [ "overriding aorta" ], [ "right ventricular hypertrophy" ], [ "patent foramen ovale" ] ], "type": "list", "id": "56be15ffef6e39474100000b", "snippets": [ { "offsetInBeginSection": 282, "offsetInEndSection": 448, "text": "Pentalogy of Fallot (POF) is a rare form of congenital heart disease characterized by the association of Tetralogy of Fallot (TOF) with an atrial septal defect (ASD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26393185", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 533, "text": "Additionally, an atrial septal defect was found on necropsy, resulting in the final diagnosis of Tetralogy of Fallot with an atrial septal defect (a subclass of Pentalogy of Fallot).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24594084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Pentalogy of Fallot is a rare cyanotic congenital heart disease characterized by biventricular origin of the aorta above a large ventricular septal defect, obstruction of the pulmonary outflow, right ventricular hypertrophy (tetralogy of Fallot), and an atrial septal defect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11432800", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 740, "text": "Postmortem examination of the ram's heart showed a pentalogy of Fallot, consisting of a pulmonic stenosis, a ventricular septal defect, an overriding aorta, a right ventricular hypertrophy and a patent foramen ovale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23758042", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 712, "text": "Additionally, an atrial septal defect was found on necropsy, resulting in the final diagnosis of Tetralogy of Fallot with an atrial septal defect (a subclass of Pentalogy of Fallot).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24594084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Pentalogy of Fallot is a rare cyanotic congenital heart disease characterized by biventricular origin of the aorta above a large ventricular septal defect, obstruction of the pulmonary outflow, right ventricular hypertrophy (tetralogy of Fallot), and an atrial septal defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11432800", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 570, "text": "Based on these findings, the dog was diagnosed as a case of tetralogy of Fallot with atrial septal defect (pentalogy of Fallot).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17283405", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 445, "text": "the dog was diagnosed as a case of tetralogy of Fallot with atrial septal defect (pentalogy of Fallot).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17283405", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 1069, "text": "In conclusion, whenever the diagnosis pentalogy of fallot is suspected, a multidisciplinary approach is essential. Pentalogy of fallot; Overriding Aorta; Ventricular Septal Defect; Atrial Septal Defect; Pulmonary Atresia; Doppler Echocardiography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461877", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 534, "text": "resulting in the final diagnosis of Tetralogy of Fallot with an atrial septal defect (a subclass of Pentalogy of Fallot).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24594084", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 449, "text": "Pentalogy of Fallot (POF) is a rare form of congenital heart disease characterized by the association of Tetralogy of Fallot (TOF) with an atrial septal defect (ASD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26393185", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 1069, "text": "In conclusion, whenever the diagnosis pentalogy of fallot is suspected, a multidisciplinary approach is essential.Pentalogy of fallot; Overriding Aorta; Ventricular Septal Defect; Atrial Septal Defect; Pulmonary Atresia; Doppler Echocardiography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461877", "endSection": "abstract" } ] }, { "body": "Which is the major function of sororin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21111234", "http://www.ncbi.nlm.nih.gov/pubmed/25173175", "http://www.ncbi.nlm.nih.gov/pubmed/25266476", "http://www.ncbi.nlm.nih.gov/pubmed/23901111", "http://www.ncbi.nlm.nih.gov/pubmed/22101327", "http://www.ncbi.nlm.nih.gov/pubmed/25220052", "http://www.ncbi.nlm.nih.gov/pubmed/25257310", "http://www.ncbi.nlm.nih.gov/pubmed/24141881", "http://www.ncbi.nlm.nih.gov/pubmed/25092792", "http://www.ncbi.nlm.nih.gov/pubmed/25092791", "http://www.ncbi.nlm.nih.gov/pubmed/21115494", "http://www.ncbi.nlm.nih.gov/pubmed/25257309", "http://www.ncbi.nlm.nih.gov/pubmed/22580470" ], "ideal_answer": [ "Sororin is a positive regulator of sister chromatid cohesion that interacts with the cohesin complex." ], "type": "summary", "id": "56f6d4ed09dd18d46b000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Sororin pre-mRNA splicing is required for proper sister chromatid cohesion in human cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25092791", "endSection": "title" }, { "offsetInBeginSection": 807, "offsetInEndSection": 912, "text": "ororin accumulation during S phase, and are, therefore, essential to the maintenance of genome stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25092791", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 530, "text": "Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25092792", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 503, "text": "the cohesion protein sororin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25257309", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 607, "text": "sororin, a factor required for the stable association of cohesin with chromatin, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25257310", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 496, "text": " sororin, a critical regulator that stabilizes cohesin rings in sister chromatids,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25266476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Sister chromatid cohesion depends on Sororin, a protein that stabilizes acetylated cohesin complexes on DNA by antagonizing the cohesin release factor Wings-apart like protein (Wapl). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23901111", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 332, "text": "Three additional factors Pds5, Wapl, and Sororin bind to cohesin and modulate its dynamic association with chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Sister chromatid cohesion, mediated by cohesin and regulated by Sororin, is essential for chromosome segregation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22101327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Sororin is a master regulator of sister chromatid cohesion and separation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22580470", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The maintenance of sister chromatid cohesion from S phase to the onset of anaphase relies on a small but evolutionarily conserved protein called Sororin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22580470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Sororin mediates sister chromatid cohesion by antagonizing Wapl.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21111234", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Sororin is a positive regulator of sister chromatid cohesion that interacts with the cohesin complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21115494", "endSection": "abstract" } ] }, { "body": "Which gene fusion is the result of the \"philadelphia translocation\" or the \"philadelphia chromosome\" mutation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12730117", "http://www.ncbi.nlm.nih.gov/pubmed/11919388", "http://www.ncbi.nlm.nih.gov/pubmed/17987804", "http://www.ncbi.nlm.nih.gov/pubmed/16616117", "http://www.ncbi.nlm.nih.gov/pubmed/2820585", "http://www.ncbi.nlm.nih.gov/pubmed/21279819", "http://www.ncbi.nlm.nih.gov/pubmed/8697423", "http://www.ncbi.nlm.nih.gov/pubmed/9916508", "http://www.ncbi.nlm.nih.gov/pubmed/8656667", "http://www.ncbi.nlm.nih.gov/pubmed/21332651", "http://www.ncbi.nlm.nih.gov/pubmed/18722880", "http://www.ncbi.nlm.nih.gov/pubmed/3670297", "http://www.ncbi.nlm.nih.gov/pubmed/2157692", "http://www.ncbi.nlm.nih.gov/pubmed/22058195", "http://www.ncbi.nlm.nih.gov/pubmed/17001000", "http://www.ncbi.nlm.nih.gov/pubmed/1423227", "http://www.ncbi.nlm.nih.gov/pubmed/1434792", "http://www.ncbi.nlm.nih.gov/pubmed/11535505", "http://www.ncbi.nlm.nih.gov/pubmed/11984797", "http://www.ncbi.nlm.nih.gov/pubmed/8490164", "http://www.ncbi.nlm.nih.gov/pubmed/22783385" ], "ideal_answer": [ "Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. The Philadelphia chromosome and its corresponding fusion gene, BCR-ABL, is one of the best-known genetic abnormalities in hematological malignancies. Major BCR-ABL translocation is much more common in chronic myelogenous leukemia (CML) and minor BCR-ABL in acute lymphoblastic leukemia. ", "Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. ", "The Philadelphia chromosome is recognized as the cytogenetic result of a rearrangement of the ABL gene on chromosome 9 and the BCL gene on chromosome 22, which leads to the creation of a BCR/ABL fusion gene on chromosome 22." ], "exact_answer": [ "The BCR/ABL gene fusion", "ABL/BCR fusion" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014178", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005694", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010677" ], "type": "factoid", "id": "55149f156a8cde6b72000013", "snippets": [ { "offsetInBeginSection": 5, "offsetInEndSection": 307, "text": "Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL) is a common cytogenetic abnormality associated with poor outcome in adults. This preliminary study, in the absence of substantial evidence, reported the prevalence of the BCR-ABL gene fusion in ALL patients by RT-PCR in Pakistan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21332651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "The Philadelphia chromosome and its corresponding fusion gene, BCR-ABL, is one of the best-known genetic abnormalities in hematological malignancies. Major BCR-ABL translocation is much more common in chronic myelogenous leukemia (CML) and minor BCR-ABL in acute lymphoblastic leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18722880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The BCR/ABL gene fusion, the hallmark of chronic myelogenous leukemia (CML) is generated in 2-10% of patients by a variant Ph translocation involving 9q34, 22q11.2, and one or more additional genomic regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16616117", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 198, "text": "The t(9;22)(q34;q11) translocation leading to the Philadelphia (Ph) chromosome resulting in BCR-ABL gene fusion is associated with a poor prognosis in acute lymphoblastic leukemia (ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11984797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11919388", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 761, "text": "Ph chromosome was identified in CML in 1960 and was found to clearly result from reciprocal translocation between chromosome 9 and chromosome 22 (t(q;22)) (q34;q11). CML arises from a single pluripotent hematopoietic stem cell with the Ph chromosome and demonstration of the Ph chromosome in blood or marrow cells establishes and unequivocal diagnosis of CML. The Ph chromosome is recognized as the cytogenetic result of a rearrangement of the ABL gene on chromosome 9 and the BCL gene on chromosome 22, which leads to the creation of a BCR/ABL fusion gene on chromosome 22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9916508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Fluorescence in situ hybridization (FISH) technique has been successfully used to detect the BCR-ABL gene fusion in chronic myeloid leukemia (CML) with the classic form of the Philadelphia chromosome (Ph).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8697423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Chronic myeloid leukaemia (CML) is characterized cytogenetically by a t(9;22)(q34;ql1) reciprocal translocation which gives origin to a hybrid BCR-ABL gene, encoding a p2lO(BCR-ABL) fusion protein with elevated tyrosine kinase activity and transforming abilities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8656667", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1351, "text": "There is a recent suggestion that the BCR-ABL gene may not be always 'functional', since extremely low levels of BCR-ABL transcripts can be found in leucocytes from normal individuals and, conversely, it appears that no BCR-ABL transcription can be detected in a proportion of Ph-positive haematopoietic progenitors from some CML patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8656667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Chronic myeloid leukemia (CML) is associated with the Philadelphia chromosome, which arises by a reciprocal translocation between chromosomes 9 and 22 and harbors the BCR-ABL fusion oncogene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17001000", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 336, "text": "The translocation event creates on the Philadelphia chromosome a fusion between two genes: bcr and abl.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1434792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Chronic myelogenous leukemia (CML) is genetically characterized by the reciprocal translocation of chromosome 9 and 22, t(9;22)(q34;q11) which results in the fusion of BCR/ABL gene observed on the derivative chromosome 22 called Philadelphia (Ph) chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17987804", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 939, "text": "Using specific probes for the BCR and ABL genes, results of FISH showed a three-way variant Philadelphia translocation (9;22;21)(q34;q11;p12) with a BCR/ABL fusion residing on the der(22) and the 3BCR region translocated on the short arm of the derivative chromosome 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22783385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 533, "text": "We report a cytogenetic study of a patient with chronic myelogenous leukemia (CML) who, while displaying a Philadelphia (Ph) chromosome, resulting from a standard t(9;22) at diagnosis, during the chronic phase (CP) showed disappearance of the Ph and occurrence of new chromosome changes, including a marker probably arising from a translocation involving chromosome 17 and the Ph. In situ hybridization confirmed the cytogenetic appearance and demonstrated that the breakpoint on the Ph marker occurred below the BCR-ABL fusion gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1423227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "The translocation of the c-abl oncogene from chromosome 9 to the bcr gene on chromosome 22 in cases of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) generates an aberrant bcr-abl fusion transcript which may be intimately related to the pathogenesis of CML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3670297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 446, "text": "In the great majority of patients with chronic myelogenous leukemia (CML) the reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), resulting in the Philadelphia (Ph) chromosome produces fusion DNA sequences consisting of the 5 part of the major breakpoint cluster region-1 (M-BCR-1) and the ABL protooncogene which encodes for the P210BCR-ABL phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2157692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2820585", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Expression of the ABL-BCR fusion gene in Philadelphia-positive acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8490164", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Chronic myelogenous leukemia (CML) is characterized by Philadelphia (Ph) chromosome with a chimeric gene BCR-ABL created by reciprocal t(9:22) (q34;q11) translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11535505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Fluorescence in situ hybridization (FISH) technique has been successfully used to detect the BCR-ABL gene fusion in chronic myeloid leukemia (CML) with the classic form of the Philadelphia chromosome (Ph)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8697423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Chronic myeloid leukemia (CML) is characterized by formation of a BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12730117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Chronic myelogenous leukemia (CML) is genetically characterized by the reciprocal translocation of chromosome 9 and 22, t(9;22)(q34;q11) which results in the fusion of BCR/ABL gene observed on the derivative chromosome 22 called Philadelphia (Ph') chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17987804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Chronic myelogenous leukemia (CML) is characterized by Philadelphia (Ph) chromosome with a chimeric gene BCR-ABL created by reciprocal t(9:22) (q34;q11) translocation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279819", "endSection": "abstract" } ] }, { "body": "Is zolpidem an antibiotic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8098760", "http://www.ncbi.nlm.nih.gov/pubmed/1403792", "http://www.ncbi.nlm.nih.gov/pubmed/11154097", "http://www.ncbi.nlm.nih.gov/pubmed/9433391", "http://www.ncbi.nlm.nih.gov/pubmed/2871178" ], "ideal_answer": [ "No, zolpidem is a short-acting imidazopyridine hypnotic drug" ], "exact_answer": "no", "concepts": [ "http://www.biosemantics.org/jochem#4205693", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000900", "http://www.biosemantics.org/jochem#4259685" ], "type": "yesno", "id": "530cf4fe960c95ad0c00000a", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 106, "text": "Zolpidem is a short-acting imidazopyridine hypnotic drug that is metabolized mainly by CYP3A4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9433391", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 719, "text": "FGIN-1-27 and alpidem, like the neurosteroid 3 alpha,21-dehydroxy-5 alpha-pregnane-20-one (THDOC), clonazepam and zolpidem (the direct allosteric modulators of gamma-aminobutyric acidA receptors) delay the onset of isoniazid and metrazol-induced convulsions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8098760", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 231, "text": "olpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8098760", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 231, "text": "lpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1403792", "endSection": "abstract" }, { "offsetInBeginSection": 1334, "offsetInEndSection": 1469, "text": "In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1403792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2871178", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Zolpidem [N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide hemitartrate] is reported to be a rapid onset, short duration hypnotic that interacts at the benzodiazepine recognition site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2871178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The imidazopyridine zolpidem is a short-acting hypnotic chemically distinct from benzodiazepines (BZs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154097", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 279, "text": "According to its peculiar neuropharmacologic activity (selectivity for the omega 1-BZ receptors), zolpidem is expected to be a pure hypnotic, without the other effects of BZs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11154097", "endSection": "abstract" } ] }, { "body": "Can desvenlafaxine be used at a dose of 50mg/day?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23587982", "http://www.ncbi.nlm.nih.gov/pubmed/21067460", "http://www.ncbi.nlm.nih.gov/pubmed/23881185", "http://www.ncbi.nlm.nih.gov/pubmed/20107296", "http://www.ncbi.nlm.nih.gov/pubmed/18507895", "http://www.ncbi.nlm.nih.gov/pubmed/23517291", "http://www.ncbi.nlm.nih.gov/pubmed/22173281", "http://www.ncbi.nlm.nih.gov/pubmed/19407711", "http://www.ncbi.nlm.nih.gov/pubmed/23473348", "http://www.ncbi.nlm.nih.gov/pubmed/19407730" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A15520455", "o": "790287" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": 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"http://linkedlifedata.com/resource/umls/id/C2682645", "o": "http://linkedlifedata.com/resource/umls/label/A16715518" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16715518", "o": "Desvenlafaxine 50 MG Extended Release Tablet" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2682645", "o": "http://linkedlifedata.com/resource/umls/id/C2341609" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2341609", "o": "http://linkedlifedata.com/resource/umls/label/A15532899" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2341609", "o": "http://linkedlifedata.com/resource/umls/label/A15532899" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15532899", "o": "Desvenlafaxine Extended Release Tablet" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C2341627", "o": "http://linkedlifedata.com/resource/umls/id/C2341629" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16715518", "o": "RXNORM" } ], "ideal_answer": [ "Yes, desvenlafaxine can be at 50mg/day to treat patients with major depressive disorder. Studies suggest that 50 mg is the minimum effective dose of desvenlafaxine for the treatment of major depressive disorder. The recommended dose of DVS ranges from 50 to 100 mg." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4266016", "http://www.biosemantics.org/jochem#4243854" ], "type": "yesno", "id": "530cf4fe960c95ad0c00000c", "snippets": [ { "offsetInBeginSection": 1331, "offsetInEndSection": 1466, "text": "Long-term use of desvenlafaxine was safe and well tolerated, with a clinical benefit/risk profile similar to that in other populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587982", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 286, "text": "e objective of this study was to evaluate the long-term safety of desvenlafaxine for continuation treatment of major depressive disorder (MDD) in Japanese patients. This was a phase 3, multicenter, 10-month, open-label study with flexible dosing of desvenlafaxine (25, 50, 100 mg/day)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587982", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 270, "text": "n an effort to establish the lowest effective dose of desvenlafaxine (administered as desvenlafaxine succinate), we assessed the efficacy, safety, and tolerability of 10- and 50-mg/day desvenlafaxine vs placebo for the treatment of major depressive disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517291", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1101, "text": "Change from baseline to final evaluation in adjusted HAM-D(17) total scores was not significantly different comparing desvenlafaxine 10 mg/day (-9.28) and desvenlafaxine 50 mg/day (-8.92) with placebo (-8.42)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517291", "endSection": "abstract" }, { "offsetInBeginSection": 1359, "offsetInEndSection": 1449, "text": "Overall rates of treatment-emergent adverse events with both doses were similar to placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517291", "endSection": "abstract" }, { "offsetInBeginSection": 1526, "offsetInEndSection": 1783, "text": "However, in a companion study reported separately, desvenlafaxine 50 mg, but not 25 mg, separated from placebo. Taken together, these studies suggest that 50 mg is the minimum effective dose of desvenlafaxine for the treatment of major depressive disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517291", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 793, "text": "Desvenlafaxine XR was dosed at 50 mg/day for 10 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22173281", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 645, "text": "Desvenlafaxine therapy is initiated at the therapeutic dose (50 mg/day) without a need for dose titration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21067460", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 764, "text": "Clinical studies have investigated the efficacy of DVS in doses ranging from 50 to 400 mg/day for the treatment of MDD in adult outpatients. The effects of DVS 50 mg/day have been clearly distinguished from placebo in the reduction of MDD symptoms in such clinical trials. No additional therapeutic benefits were found at doses > 50 mg/day. The recommended dose of DVS ranges from 50 to 100 mg.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20107296", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 668, "text": "Adult outpatients with major depressive disorder received desvenlafaxine doses ranging from 50-400 mg/day or placebo for 8 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19407730", "endSection": "abstract" }, { "offsetInBeginSection": 2422, "offsetInEndSection": 2533, "text": " At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19407730", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 483, "text": "atients received fixed (50, 100, 200, or 400 mg/day; n=1,342) or flexible doses (100-400 mg/day; n=463) of desvenlafaxine or placebo (n=1,108)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19407711", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1493, "text": "Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19407711", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 249, "text": "To assess the efficacy, safety, and tolerability of 50- and 100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a serotonin-norepinephrine reuptake inhibitor, for the treatment of major depressive disorder (MDD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18507895", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 581, "text": "Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale for Depression (HAM-D(17)) scores > or =20 were randomly assigned to double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 mg/day) for 8 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18507895", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1093, "text": "Desvenlafaxine 50 mg was associated with a significantly greater adjusted mean change from baseline on the HAM-D(17) (-11.5) compared with placebo (-9.5, p=0.018)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18507895", "endSection": "abstract" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1809, "text": " These results demonstrate efficacy, safety, and tolerability of desvenlafaxine 50 mg/day for treating MDD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18507895", "endSection": "abstract" }, { "offsetInBeginSection": 1720, "offsetInEndSection": 1956, "text": "CONCLUSIONS: Desvenlafaxine at the recommended dose of 50 mg/d was effective in relapse prevention of depression during a 6-month period in patients who demonstrated stable response after 20 weeks of open-label desvenlafaxine treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473348", "endSection": "abstract" } ] }, { "body": "Which syndrome is associated with OATP1B1 and OATP1B3 deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "http://www.ncbi.nlm.nih.gov/pubmed/22232210" ], "ideal_answer": [ "Complete and simultaneous deficiency of the organic anion transporting polypeptides OATP1B1 and OATP1B3 due to mutations in their corresponding genes, has been linked to Rotor syndrome." ], "exact_answer": [ "Rotor syndrome" ], "type": "factoid", "id": "571e40a8bb137a4b0c000009", "snippets": [ { "offsetInBeginSection": 518, "offsetInEndSection": 741, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 1632, "offsetInEndSection": 1785, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "title" }, { "offsetInBeginSection": 738, "offsetInEndSection": 961, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 961, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 1864, "offsetInEndSection": 2104, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 1775, "offsetInEndSection": 1927, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "title" }, { "offsetInBeginSection": 518, "offsetInEndSection": 740, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 742, "text": "The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that of Rotor syndrome, an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics, has remained enigmatic. Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 742, "text": "The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that of Rotor syndrome, an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics, has remained enigmatic. Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 902, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3. These important detoxification-limiting proteins mediate uptake and clearance of countless drugs and drug conjugates across the sinusoidal hepatocyte membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 902, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3. These important detoxification-limiting proteins mediate uptake and clearance of countless drugs and drug conjugates across the sinusoidal hepatocyte membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 1634, "offsetInEndSection": 1874, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1874, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia. Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "title" }, { "offsetInBeginSection": 519, "offsetInEndSection": 742, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 742, "text": "Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1785, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" } ] }, { "body": "Which type of lung cancer is afatinib used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21554040", "http://www.ncbi.nlm.nih.gov/pubmed/22452896", "http://www.ncbi.nlm.nih.gov/pubmed/24086949", "http://www.ncbi.nlm.nih.gov/pubmed/18408761", "http://www.ncbi.nlm.nih.gov/pubmed/23664448", "http://www.ncbi.nlm.nih.gov/pubmed/18520300", "http://www.ncbi.nlm.nih.gov/pubmed/22071596", "http://www.ncbi.nlm.nih.gov/pubmed/23683257" ], "ideal_answer": [ "Afatinib is a small molecule covalently binding and inhibiting the EGFR, HER2 and HER4 receptor tyrosine kinases. Trials showed promising efficacy in patients with EGFR-mutant NSCLC or enriched for clinical benefit from EGFR tyrosine kinase inhibitors gefitinib or erlotinib.", "Afatinib is a novel irreversible inhibitor of the ErbB family members EGFR, tyrosine kinase-type cell surface receptors HER2 and HER4. It shows preclinical efficacy in NSCLC with common EGFR-activating mutations and the T790M mutation typically associated with EGFR TKI resistanceBIBW2992 is an irreversible EGFR TKI that also inhibits HER2 and vascular epidermal growth factor receptors" ], "exact_answer": [ "EGFR-mutant non small cell lung carcinoma", "EGFR-mutant NSCLC" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.disease-ontology.org/api/metadata/DOID:3683", "http://www.disease-ontology.org/api/metadata/DOID:7696", "http://www.disease-ontology.org/api/metadata/DOID:3908", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008175", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008171", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008168", "http://www.disease-ontology.org/api/metadata/DOID:1324" ], "type": "factoid", "id": "530cf4fe960c95ad0c00000b", "snippets": [ { "offsetInBeginSection": 611, "offsetInEndSection": 891, "text": "Afatinib is a novel irreversible inhibitor of the ErbB family members EGFR, tyrosine kinase-type cell surface receptors HER2 and HER4. It shows preclinical efficacy in NSCLC with common EGFR-activating mutations and the T790M mutation typically associated with EGFR TKI resistance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086949", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 978, "text": "At present, only first-generation EGFR-tyrosine kinase inhibitors (TKIs) (erlotinib and gefitinib) are available for clinical use. Second-generation irreversible EGFR-TKIs, such as afatinib, are still in clinical trials. In current clinical practice, EGFR-TKI is the first-line treatment of choice for metastatic NSCLC patients with tumor EGFR mutation or as salvage therapy in NSCLC patients who received systemic chemotherapy previously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23683257", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 1249, "text": "Afatinib is a small molecule covalently binding and inhibiting the EGFR, HER2 and HER4 receptor tyrosine kinases. In preclinical studies, afatinib not only inhibited the growth of models with common activating EGFR mutations, but was also active in lung cancer models harboring wild-type EGFR or the EGFR L858R/T790M double mutant. Clinical efficacy of afatinib has been extensively studied in the LUX-Lung study program. These trials showed promising efficacy in patients with EGFR-mutant NSCLC or enriched for clinical benefit from EGFR tyrosine kinase inhibitors gefitinib or erlotinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23664448", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1394, "text": "BIBW2992 is an irreversible EGFR TKI that also inhibits HER2 and vascular epidermal growth factor receptors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18520300", "endSection": "abstract" }, { "offsetInBeginSection": 1396, "offsetInEndSection": 1559, "text": "In vitro work shows that this compound inhibits wild-type EGFR, EGFR exon 19 deletion, EGFR L858R, and EGFR T790M, the mutation associated with acquired resistance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18520300", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1104, "text": "Here, we show that BIBW2992, an anilino-quinazoline designed to irreversibly bind EGFR and HER2, potently suppresses the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18408761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22452896", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22071596", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554040", "endSection": "title" } ] }, { "body": "Can ferric carboxymaltose be used to treat anemia in inflammatory bowel disease patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21340038", "http://www.ncbi.nlm.nih.gov/pubmed/19787830", "http://www.ncbi.nlm.nih.gov/pubmed/20648930", "http://www.ncbi.nlm.nih.gov/pubmed/23078888", "http://www.ncbi.nlm.nih.gov/pubmed/23889159", "http://www.ncbi.nlm.nih.gov/pubmed/24114623", "http://www.ncbi.nlm.nih.gov/pubmed/21479141", "http://www.ncbi.nlm.nih.gov/pubmed/22023204", "http://www.ncbi.nlm.nih.gov/pubmed/18371137", "http://www.ncbi.nlm.nih.gov/pubmed/21699794", "http://www.ncbi.nlm.nih.gov/pubmed/23644823", "http://www.ncbi.nlm.nih.gov/pubmed/24081613", "http://www.ncbi.nlm.nih.gov/pubmed/22179489" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A13386134", "o": "C522335" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2001867", "o": "http://linkedlifedata.com/resource/umls/label/A13386134" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A13386134", "o": "ferric carboxymaltose" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2001867", "o": "http://linkedlifedata.com/resource/umls/label/A13386134" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A13386134", "o": "MeSH" } ], "ideal_answer": [ "Ferric carboxymaltose can be used to treat anemia in patients with inflammatory bowel disease, and prevents recurrence of anemia in these patients, compared with placebo. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003093", "http://www.disease-ontology.org/api/metadata/DOID:2355", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005290", "http://www.disease-ontology.org/api/metadata/DOID:0050589", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015212", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009220" ], "type": "yesno", "id": "530cf4fe960c95ad0c00000d", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 805, "text": "Intravenous iron should be preferred where oral iron is poorly tolerated or where it has failed in moderate to severe anemia, and in combination with erythropoietin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114623", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1069, "text": "Ferric carboxymaltose is much more convenient, and has been shown to be more effective than iron sucrose in a large randomized tria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114623", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 84, "text": "nemia and iron deficiency anemia are very common in inflammatory bowel disease (IBD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24114623", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 941, "text": "Ferric carboxymaltose was associated with cost savings of 30-44\u00a0% per patient per treatment cycle compared to iron sucrose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24081613", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 385, "text": "Iron deficiency is common in pregnancy, postpartum, inflammatory bowel disease, chronic kidney disease, chronic heart failure, heavy uterine bleeding, cancer and following surgery. We estimate the budget impact (BI) on the Swiss mandatory health insurance associated with substituting iron sucrose (standard) with ferric carboxymaltose (new treatment) using real-life data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24081613", "endSection": "abstract" }, { "offsetInBeginSection": 1438, "offsetInEndSection": 1583, "text": "reating iron deficiency involves substantial costs to the Swiss MHI which may be reduced by substituting iron sucrose with ferric carboxymaltose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24081613", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 347, "text": "e aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23889159", "endSection": "abstract" }, { "offsetInBeginSection": 1658, "offsetInEndSection": 1766, "text": "FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23644823", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 777, "text": "We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23644823", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 410, "text": "e performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23078888", "endSection": "abstract" }, { "offsetInBeginSection": 1670, "offsetInEndSection": 1749, "text": "FCM prevents recurrence of anemia in patients with IBD, compared with placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23078888", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 403, "text": " A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22179489", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1332, "text": "Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22179489", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1001, "text": " Intravenous iron avoids these concerns, especially with the development of ferric carboxymaltose, which allow up to 1000mg to be given rapidly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "What is the optimal treatment for anemia in inflammatory bowel disease?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023204", "endSection": "title" }, { "offsetInBeginSection": 237, "offsetInEndSection": 441, "text": "We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21699794", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1447, "text": "Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21699794", "endSection": "abstract" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1706, "text": " The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21699794", "endSection": "abstract" }, { "offsetInBeginSection": 1450, "offsetInEndSection": 1701, "text": "Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21340038", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 970, "text": " Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21340038", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 723, "text": "Ferric carboxymaltose can be administered at 15 mg/kg body weight to a maximum dose of 1000 mg, whereas iron isomaltoside 1000 can be administered at 20 mg/kg body weight. The ability to give high doses of iron is important in the context of managing iron deficiency anemia in a number of clinical conditions where demands for iron are high (including chronic blood loss associated with inflammatory bowel disease, menorrhagia, and chronic kidney disease)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479141", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 456, "text": "erric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648930", "endSection": "abstract" }, { "offsetInBeginSection": 1306, "offsetInEndSection": 1404, "text": "In patients with IBD or PPA, improvements in Hb levels were more rapid with FCM than with FeSulf. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648930", "endSection": "abstract" }, { "offsetInBeginSection": 2101, "offsetInEndSection": 2263, "text": "CM improved patient quality of life to an equivalent extent to oral FeSulf in patients with IBD or PPA, and to a greater extent than oral FeSulf in women with AUB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648930", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1205, "text": "Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19787830", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 104, "text": "he prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19787830", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 158, "text": " novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371137", "endSection": "title" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1544, "text": "FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371137", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1342, "text": "Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371137", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 812, "text": "The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority (P= 0.6967). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23078888", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 458, "text": "Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648930", "endSection": "abstract" } ] }, { "body": "Which disease is treated with Eliglustat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25256118", "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "http://www.ncbi.nlm.nih.gov/pubmed/24835462", "http://www.ncbi.nlm.nih.gov/pubmed/20864621", "http://www.ncbi.nlm.nih.gov/pubmed/25819691", "http://www.ncbi.nlm.nih.gov/pubmed/20439622", "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "http://www.ncbi.nlm.nih.gov/pubmed/22058426", "http://www.ncbi.nlm.nih.gov/pubmed/20713962" ], "ideal_answer": [ "Eliglustat was developed for treatment of Gaucher's disease type 1." ], "exact_answer": [ "Gaucher's disease type 1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019468", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194" ], "type": "factoid", "id": "56c1f009ef6e39474100003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Eliglustat compared with imiglucerase in patients with Gaucher's disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomised, open-label, non-inferiority trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25819691", "endSection": "title" }, { "offsetInBeginSection": 131, "offsetInEndSection": 292, "text": "We investigated whether patients stable on such treatment would remain so after switching to oral eliglustat, a selective inhibitor of glucosylceramide synthase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25819691", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 682, "text": "Patients were randomly allocated 2:1 at 39 clinics (stratified by ERT dose; block sizes of four; computer-generated centrally) to receive either oral eliglustat or imiglucerase infusions for 12 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25819691", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1312, "text": "The non-inferiority margin was 25% for eliglustat relative to imiglucerase, assessed in all patients who completed 12 months of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25819691", "endSection": "abstract" }, { "offsetInBeginSection": 2265, "offsetInEndSection": 2468, "text": "NTERPRETATION: Oral eliglustat maintained haematological and organ volume stability in adults with Gaucher's disease type 1 already controlled by intravenous ERT and could be a useful therapeutic option.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25819691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "endSection": "title" }, { "offsetInBeginSection": 164, "offsetInEndSection": 338, "text": "OBJECTIVE: To determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "endSection": "abstract" }, { "offsetInBeginSection": 2080, "offsetInEndSection": 2338, "text": "CONCLUSIONS AND RELEVANCE: Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 885, "text": "To explore the relationship between B-cell malignancy and the biochemical defect, we treated Gaucher mice with eliglustat tartrate (GENZ 112638), a potent and selective inhibitor of the first committed step in glycosphingolipid biosynthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25256118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "OBJECTIVE: Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "abstract" }, { "offsetInBeginSection": 1595, "offsetInEndSection": 1695, "text": "CONCLUSIONS: Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439622", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20713962", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20713962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24835462", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Three phase 1 studies of eliglustat tartrate (Genz-112638), an oral inhibitor of glucosylceramide synthase under development for treating Gaucher disease type 1 (GD1), evaluated the safety, tolerability, and pharmacokinetics in healthy volunteers after escalating single doses (n = 99), escalating multiple doses (n = 36), and food (n = 24). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20864621", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1695, "text": "At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved.CONCLUSIONS: Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058426", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 582, "text": "A safe, effective oral therapy is needed.OBJECTIVE: To determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1.DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 12 countries from November 2009 to July 2012 among eligible patients with splenomegaly plus thrombocytopenia and/or anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "endSection": "abstract" }, { "offsetInBeginSection": 1942, "offsetInEndSection": 2338, "text": "One patient in the eliglustat group withdrew (non-treatment related); 39 of the 40 patients transitioned to an open-label extension study.CONCLUSIONS AND RELEVANCE: Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 464, "text": "A multinational, open-label, single-arm phase 2 study of 26 GD1 patients (16 female, 10 male; mean age, 34 years) evaluated the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered twice daily by mouth at 50- or 100-mg doses based on plasma drug concentrations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439622", "endSection": "abstract" }, { "offsetInBeginSection": 1558, "offsetInEndSection": 1649, "text": " Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "abstract" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1646, "text": "At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": " Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy. Eliglustat tartrate improved clinical manifestations in patients who received 50 or 100 mg twice daily for 1 year during an open-label phase 2 study (Blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20713962", "endSection": "abstract" }, { "offsetInBeginSection": 1847, "offsetInEndSection": 2216, "text": "One patient in the eliglustat group withdrew (non-treatment related); 39 of the 40 patients transitioned to an open-label extension study. Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "endSection": "abstract" }, { "offsetInBeginSection": 1558, "offsetInEndSection": 1646, "text": "Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058426", "endSection": "abstract" }, { "offsetInBeginSection": 1847, "offsetInEndSection": 2216, "text": "One patient in the eliglustat group withdrew (non-treatment related); 39 of the 40 patients transitioned to an open-label extension study.Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 524, "text": "Three phase 1 studies of eliglustat tartrate (Genz-112638), an oral inhibitor of glucosylceramide synthase under development for treating Gaucher disease type 1 (GD1), evaluated the safety, tolerability, and pharmacokinetics in healthy volunteers after escalating single doses (n = 99), escalating multiple doses (n = 36), and food (n = 24). Eliglustat tartrate was well tolerated at single doses \u2264 20 mg/kg and multiple doses \u2264 200 mg bid, with 50 mg bid producing plasma concentrations in the predicted therapeutic range.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20864621", "endSection": "abstract" } ] }, { "body": "List algorithms suitable for predicting protein complexes", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16872538", "http://www.ncbi.nlm.nih.gov/pubmed/24299017", "http://www.ncbi.nlm.nih.gov/pubmed/22174556", "http://www.ncbi.nlm.nih.gov/pubmed/21682895", "http://www.ncbi.nlm.nih.gov/pubmed/19534736", "http://www.ncbi.nlm.nih.gov/pubmed/23419374", "http://www.ncbi.nlm.nih.gov/pubmed/22894160", "http://www.ncbi.nlm.nih.gov/pubmed/21047377", "http://www.ncbi.nlm.nih.gov/pubmed/22685080", "http://www.ncbi.nlm.nih.gov/pubmed/19435747", "http://www.ncbi.nlm.nih.gov/pubmed/23210476", "http://www.ncbi.nlm.nih.gov/pubmed/18574858", "http://www.ncbi.nlm.nih.gov/pubmed/22990765", "http://www.ncbi.nlm.nih.gov/pubmed/23046740", "http://www.ncbi.nlm.nih.gov/pubmed/22165822", "http://www.ncbi.nlm.nih.gov/pubmed/22711784", "http://www.ncbi.nlm.nih.gov/pubmed/24214996", "http://www.ncbi.nlm.nih.gov/pubmed/23688127", "http://www.ncbi.nlm.nih.gov/pubmed/24144986", "http://www.ncbi.nlm.nih.gov/pubmed/17094256", "http://www.ncbi.nlm.nih.gov/pubmed/21721046", "http://www.ncbi.nlm.nih.gov/pubmed/22488467", "http://www.ncbi.nlm.nih.gov/pubmed/22185599", "http://www.ncbi.nlm.nih.gov/pubmed/24565338", "http://www.ncbi.nlm.nih.gov/pubmed/17688314" ], "ideal_answer": [ "Protein-Protein interactions (PPI) play a key role in determining the outcome of most cellular processes. The correct identification and characterization of protein interactions and the networks, which they comprise, is critical for understanding the molecular mechanisms within the cell. Large-scale techniques such as pull down assays and tandem affinity purification are used in order to detect protein interactions in an organism. Today, relatively new high-throughput methods like yeast two hybrid, mass spectrometry, microarrays, and phage display are also used to reveal protein interaction networks. Some suitable algorithms for predicting protein complexes are Naive Bayes Classifier, Negatome, Support Vector Machine, PEWCC, iPTMClust, NDComplex, PROCOMOSS, PPI network, metaPIS, EPOF, EAGLE, NFC, MCODE, DPClus, IPCA, CPM, MCL, CMC, SPICi, Core-Attachment, ProRank, ClusterONE, CFinder, Spectral, RNSC, Affinity Propagation, HKC, NWE, CP-DR, Struct2net and PIPE." ], "exact_answer": [ [ "Na\u00efve Bayes Classifier" ], [ "Negatome" ], [ "Support Vector Machine" ], [ "PEWCC" ], [ "iPTMClust" ], [ "NDComplex" ], [ "PROCOMOSS" ], [ "PPI network" ], [ "metaPIS" ], [ "EPOF" ], [ "EAGLE" ], [ "NFC" ], [ "MCODE" ], [ "DPClus" ], [ "IPCA" ], [ "CPM" ], [ "MCL" ], [ "CMC" ], [ "SPICi" ], [ "Core-Attachment" ], [ "ProRank" ], [ "ClusterONE" ], [ "CFinder" ], [ "Spectral" ], [ "RNSC" ], [ "Affinity Propagation" ], [ "HKC" ], [ "NWE" ], [ "CP-DR" ], [ "Struct2net" ], [ "PIPE" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005544", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000465", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046912", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043234" ], "type": "list", "id": "5333f728d6d3ac6a34000041", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 106, "text": "Protein complexes are basic cellular entities that carry out the functions of their components", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24299017", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 808, "text": "we have designed several features characterizing heterodimeric protein complexes based on genomic data sets, and proposed a supervised-learning method for the prediction of heterodimeric protein complexes. This method learns the parameters of the features, which are embedded in the na\u00efve Bayes classifier", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24299017", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 247, "text": " non-interacting proteins (NIPs) is important for training the algorithms to predict protein-protein interactions (PPIs) and for assessing the false positive rates of PPI detection efforts. We present the second version of Negatome,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214996", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 539, "text": "Negatome is derived by manual curation of literature and by analyzing three-dimensional structures of protein complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214996", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 132, "text": "Identification of protein-ligand binding site is an important task in structure-based drug design and docking algorithms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24144986", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 713, "text": "Support Vector Machine (SVM) is used to cluster the pockets that are most likely to bind ligands with the attributes of geometric characteristics, interaction potential, offset from protein, conservation score and properties surrounding the pockets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24144986", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 318, "text": "Predicting protein complexes from protein-protein interaction data is becoming a fundamental problem in computational biology. The identification and characterization of protein complexes implicated are crucial to the understanding of the molecular events under normal and abnormal physiological conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688127", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 1066, "text": "a novel graph mining algorithm (PEWCC) to identify such protein complexes. Firstly, the algorithm assesses the reliability of the interaction data, then predicts protein complexes based on the concept of weighted clustering coefficient. To demonstrate the effectiveness of the proposed method, the performance of PEWCC was compared to several methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688127", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 975, "text": "We developed a novel PTM refinement algorithm, iPTMClust, which extends a recently introduced PTM refinement algorithm PTMClust and uses a non-parametric Bayesian model to better account for uncertainties in the quantity and identity of PTMs in the input data. The use of this new modeling approach enables iPTMClust to provide a confidence score per modification site that allows fine-tuning and interpreting resulting PTM predictions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419374", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 806, "text": "We develop an algorithm for identifying protein complexes by considering these two types of complexes separately. We test our algorithm on a few yeast protein interaction networks, and show that our algorithm is able to identify complexes more accurately than existing algorithms. A software program NDComplex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23210476", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 309, "text": "Studying protein complexes is very important in biological processes since it helps reveal the structure-functionality relationships in biological networks and much attention has been paid to accurately predict protein complexes from the increasing amount of protein-protein interaction (PPI) data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046740", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 923, "text": " To provide an investigation of the roles of edges in PPI networks, we show that the edges connecting less similar vertices in topology are more significant in maintaining the global connectivity, indicating the weak ties phenomenon in PPI networks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046740", "endSection": "abstract" }, { "offsetInBeginSection": 64, "offsetInEndSection": 228, "text": "Identification of protein complexes in protein-protein interaction (PPI) networks is the first step in understanding the organization and dynamics of cell function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990765", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 629, "text": "We have developed an algorithm PROCOMOSS (Protein Complex Detection using Multi-objective Evolutionary Approach based on Semantic Similarity) for partitioning the whole PPI network into clusters, which serve as predicted protein complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990765", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 372, "text": "With the exponentially growing amount of protein sequence data, an exploration of new methods that predict protein interaction sites based solely on sequence information is becoming increasingly urgent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894160", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 761, "text": "This paper describes a new method that predicts interaction sites based on protein sequences by integrating five different algorithms employing meta-method, Majority Vote and SVMhmm Regression techniques", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894160", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 824, "text": "The 'metaPIS' web-server was implemented for meta-prediction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894160", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 614, "text": " In this paper, a novel protein complex identifying method, named EPOF, is proposed, using essential proteins and the local metric of vertex fitness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22711784", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1715, "text": "We compare the performances of EPOF to other ten previous algorithms, including EAGLE, NFC, MCODE, DPClus, IPCA, CPM, MCL, CMC, SPICi, and Core-Attachment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22711784", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1217, "text": " We compare the performance of ProRank to some of the well known protein complex prediction methods (ClusterONE, CMC, CFinder, MCL, MCode and Core) in terms of precision and recall", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22685080", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 943, "text": "In this paper we evaluated four different clustering algorithms using six different interaction datasets. We parameterized the MCL, Spectral, RNSC and Affinity Propagation algorithms and applied them to six PPI datasets produced experimentally by Yeast 2 Hybrid (Y2H) and Tandem Affinity Purification (TAP) methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185599", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 609, "text": "this paper, we present a new topology-based algorithm, HKC, to detect protein complexes in genome-scale PPI networks. HKC mainly uses the concepts of highest k-core and cohesion to predict protein complexes by identifying overlapping clusters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22174556", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 313, "text": " Protein complexes are important entities to organize various biological processes in the cell, like signal transduction, gene expression, and molecular transmission. In most cases, proteins perform their intrinsic tasks in association with their specific interacting partners, forming protein complexe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22165822", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 1418, "text": "Macropol et al. proposed a protein complex prediction algorithm, called RRW, which repeatedly expands a current cluster of proteins according to the stationary vector of a random walk with restarts with the cluster whose proteins are equally weighted. In the cluster expansion, all the proteins within the cluster have equal influences on determination of newly added protein to the cluster. In this paper, we extend the RRW algorithm by introducing a random walk with restarts with a cluster of proteins, each of which is weighted by the sum of the strengths of supporting evidence for the direct physical interactions involving the protein. The resulting algorithm is called NWE (Node-Weighted Expansion of clusters of proteins). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22165822", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1122, "text": "In this paper, we propose a new topological model by extending the definition of k-clique community of algorithm CPM and introduced distance restriction, and develop a novel algorithm called CP-DR based on the new topological model for identifying protein complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21047377", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 747, "text": "This paper also describes a random forest classifier which can effectively combine the structure-based prediction results and other functional annotations together to predict protein interactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17094256", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 764, "text": "Here we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16872538", "endSection": "abstract" } ] }, { "body": "What are piggyBAC transposons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21948799", "http://www.ncbi.nlm.nih.gov/pubmed/23358416", "http://www.ncbi.nlm.nih.gov/pubmed/22155246", "http://www.ncbi.nlm.nih.gov/pubmed/21447194", "http://www.ncbi.nlm.nih.gov/pubmed/23149543", "http://www.ncbi.nlm.nih.gov/pubmed/23476064", "http://www.ncbi.nlm.nih.gov/pubmed/20080581", "http://www.ncbi.nlm.nih.gov/pubmed/17164785", "http://www.ncbi.nlm.nih.gov/pubmed/21247877", "http://www.ncbi.nlm.nih.gov/pubmed/21822869", "http://www.ncbi.nlm.nih.gov/pubmed/21516337", "http://www.ncbi.nlm.nih.gov/pubmed/16096065", "http://www.ncbi.nlm.nih.gov/pubmed/21205896", "http://www.ncbi.nlm.nih.gov/pubmed/18354502", "http://www.ncbi.nlm.nih.gov/pubmed/20947725", "http://www.ncbi.nlm.nih.gov/pubmed/19471016", "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "http://www.ncbi.nlm.nih.gov/pubmed/20104210", "http://www.ncbi.nlm.nih.gov/pubmed/19809403", "http://www.ncbi.nlm.nih.gov/pubmed/24164672" ], "ideal_answer": [ "The piggyBAC transposons are a nonviral gene delivery approach, that have been developed as tools for insertional mutagenesis. It can mobilize 100-kb DNA fragments in mouse embryonic stem (ES) cells, making it the only known transposon with such a large cargo capacity. The integrity of the cargo is maintained during transposition, the copy number can be controlled and the inserted giant transposons express the genomic cargo. Furthermore, these 100-kb transposons can also be excised from the genome without leaving a footprint. The development of piggyBac as a large cargo vector will facilitate a wider range of genetic and genomic applications." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004251" ], "type": "summary", "id": "56c4bbfdb04e159d0e000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The Sleeping Beauty and PiggyBac DNA transposon systems have recently been developed as tools for insertional mutagenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19391106", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 627, "text": "The use of nonviral gene delivery approaches in conjunction with the latest generation transposon technology based on Sleeping Beauty (SB) or piggyBac transposons may potentially overcome some of these limitations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19471016", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 954, "text": "DNA transposons have emerged as flexible and efficient molecular vehicles to mediate stable cargo transfer. However, the ability to carry DNA fragments>10 kb is limited in most DNA transposons. Here, we show that the DNA transposon piggyBac can mobilize 100-kb DNA fragments in mouse embryonic stem (ES) cells, making it the only known transposon with such a large cargo capacity. The integrity of the cargo is maintained during transposition, the copy number can be controlled and the inserted giant transposons express the genomic cargo. Furthermore, these 100-kb transposons can also be excised from the genome without leaving a footprint. The development of piggyBac as a large cargo vector will facilitate a wider range of genetic and genomic applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21948799", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 570, "text": "In this report, we harnessed the highly efficient, nonviral, and plasmid-based piggyBac transposon system to enable concurrent genomic integration of multiple independent transposons harboring distinct protein-coding DNA sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080581", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 308, "text": "Among the transposons active in mammalian cells, the moth-derived transposon piggyBac is most promising with its highly efficient transposition, large cargo capacity, and precise repair of the donor site", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21205896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Transposons are promising systems for somatic gene integration because they can not only integrate exogenous genes efficiently, but also be delivered to a variety of organs using a range of transfection methods. piggyBac (PB) transposon has a high transposability in mammalian cells in vitro, and has been used for genetic and preclinical studies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20104210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Simple piggyBac transposon-based mammalian cell expression system for inducible protein production.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23476064", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The piggyBac transposon displays local and distant reintegration preferences and can cause mutations at noncanonical integration sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23358416", "endSection": "title" }, { "offsetInBeginSection": 313, "offsetInEndSection": 702, "text": "The piggyBac transposon was developed as an alternative mutagenic vector for mutagenesis of non-P-element targeted genes in Drosophila because the piggyBac transposon can more randomly integrate into the genome. Previous studies suggested that the piggyBac transposon always excises precisely from the insertion site without initiating a deletion or leaving behind an additional footprint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155246", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1273, "text": "A single injection of piggyBac transposons could achieve long-term inducible gene expression in the livers of mice in vivo, confirming our multiple-transposon strategy used in cultured cells. The plasmid-based piggyBac transposon system enables constitutive or inducible gene expression in vivo for potential therapeutic and biological applications without using viral vectors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19809403", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 835, "text": "In this report, we harnessed the highly efficient, nonviral, and plasmid-based piggyBac transposon system to enable concurrent genomic integration of multiple independent transposons harboring distinct protein-coding DNA sequences. Flow cytometry of cell clones derived from a single multiplexed transfection demonstrated approximately 60% (three transposons) or approximately 30% (four transposons) stable coexpression of all delivered transgenes with selection for a single marker transposon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20080581", "endSection": "abstract" } ] }, { "body": "Is there any association of the chromosomal region harboring the gene ITIH3 with schizophrenia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22614287", "http://www.ncbi.nlm.nih.gov/pubmed/24373612", "http://www.ncbi.nlm.nih.gov/pubmed/25136889", "http://www.ncbi.nlm.nih.gov/pubmed/25414627", "http://www.ncbi.nlm.nih.gov/pubmed/24618187", "http://www.ncbi.nlm.nih.gov/pubmed/24461634", "http://www.ncbi.nlm.nih.gov/pubmed/21926972", "http://www.ncbi.nlm.nih.gov/pubmed/21926974" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/P56652", "o": "http://linkedlifedata.com/resource/#_5035363635320014" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5035363635320011", "o": "Inter-alpha-inhibitor heavy chain 3" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5035363635320014", "o": "ITIH3" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5035363635320011", "o": "ITI-HC3" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5035363635320011", "o": "Inter-alpha-trypsin inhibitor heavy chain H3" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5035363635320011", "o": "ITI heavy chain H3" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11649840", "o": "6168" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11649841", "o": "H3P" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17763944", "o": "ITIH3" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16692007", "o": "pre-alpha (globulin) inhibitor, H3 polypeptide" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A12006059" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6901933", "o": "ITIH3 gene" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12006059", "o": "INTER-ALPHA-TRYPSIN INHIBITOR, HEAVY CHAIN 3" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A11649841" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A16692008" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A17748015" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11649840", "o": "inter-alpha (globulin) inhibitor H3" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A16692007" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A17763944" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A11948666" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A17748015" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16692008", "o": "inter-alpha-trypsin inhibitor heavy chain H3" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A6901933" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/label/A11649840" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11649841", "o": "6168" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16692007", "o": "6168" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16692008", "o": "6168" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17748015", "o": "6168" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17763944", "o": "6168" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0063693", "o": "http://linkedlifedata.com/resource/umls/id/C1453112" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11866112", "o": "Inter alpha trypsin inhibitor" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6956473", "o": "inter-alpha-trypsin inhibitor, heavy chain" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0195956", "o": "inter-alpha-inhibitor" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1453112", "o": "http://linkedlifedata.com/resource/umls/label/A7833732" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1453112", "o": "http://linkedlifedata.com/resource/umls/label/A6970526" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6956403", "o": "SHAP protein" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7833732", "o": "ITIH3 protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1453112", "o": "http://linkedlifedata.com/resource/umls/label/A7833732" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0235686", "o": "Trypsin inhibitor, inter-alpha-" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6988771", "o": "pre-alpha (globulin) inhibitor, H3 polypeptide, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6970526", "o": "Inter-alpha-inhibitor heavy chain 3 protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1453112", "o": "http://linkedlifedata.com/resource/umls/label/A6988771" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0195957", "o": "inter-alpha-trypsin inhibitor" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R115190989", "o": "http://linkedlifedata.com/resource/umls/id/C1416508" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C1416508", "o": "http://linkedlifedata.com/resource/umls/relation/R109169453" } ], "ideal_answer": [ "Yes, genome-wide significant associations in schizophrenia has been linked to the locus harboring the ITIH3/4 genes." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1229", "http://www.uniprot.org/uniprot/ITIH3_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012559", "http://www.uniprot.org/uniprot/ITIH3_RABIT", "http://www.biosemantics.org/jochem#4252946", "http://www.uniprot.org/uniprot/ITIH3_PONAB", "http://www.disease-ontology.org/api/metadata/DOID:5419", "http://www.uniprot.org/uniprot/ITIH3_MESAU" ], "type": "yesno", "id": "54d63d873706e89528000006", "snippets": [ { "offsetInBeginSection": 807, "offsetInEndSection": 1000, "text": "The most widely shared subset of genes-common to five of six disorders-included ANK3, AS3MT, CACNA1C, CACNB2, CNNM2, CSMD1, DPCR1, ITIH3, NT5C2, PPP1R11, SYNE1, TCF4, TENM4, TRIM26, and ZNRD1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25414627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22614287", "endSection": "title" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1053, "text": "After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22614287", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1195, "text": "In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 \u00d7 10(-9)), ANK3 (rs10994359, P = 2.5 \u00d7 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 \u00d7 10(-9)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21926974", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 901, "text": "Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21926972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24373612", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1336, "text": "We detected a novel association between suicide attempt and the ITIH3/4-region in a combined group of patients with BD, SCZ and related psychosis spectrum disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24461634", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1221, "text": "These include variations in chromosomal structure at 16p11.2, rare de novo point mutations at the gene SCN2A, and common single nucleotide polymorphisms (SNPs) mapping near loci encoding the genes ITIH3, AS3MT, CACNA1C and CACNB2. These selected examples point to the challenges to current diagnostic approaches. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24618187", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1271, "text": "STAB1 is located in close proximity to PBMR1 and the NEK4-ITIH1-ITIH3-ITIH4 region, which are the top findings from GWAS meta-analyses of mood disorder, and a combined BD and schizophrenia data set.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25136889", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1499, "text": "Our findings suggest that rs2535629 influences the susceptibility to psychiatric disorders by affecting the expression level of GLT8D1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24373612", "endSection": "abstract" } ] }, { "body": "Is APOBEC3B protein predominantly cytoplasmic or nuclear?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21715505", "http://www.ncbi.nlm.nih.gov/pubmed/18667511", "http://www.ncbi.nlm.nih.gov/pubmed/23388464", "http://www.ncbi.nlm.nih.gov/pubmed/22446380", "http://www.ncbi.nlm.nih.gov/pubmed/16648136", "http://www.ncbi.nlm.nih.gov/pubmed/23389445" ], "ideal_answer": [ "Contrary to other APOBEC family members, APOBEC3B was found to predominantly concentrate to the cell nucleus." ], "exact_answer": [ " nuclear" ], "concepts": [ "http://www.uniprot.org/uniprot/ABC3B_HUMAN" ], "type": "factoid", "id": "54e0ace81388e8454a000010", "snippets": [ { "offsetInBeginSection": 350, "offsetInEndSection": 418, "text": "A3B is the only family member with steady-state nuclear localization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446380", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 685, "text": "Here, we show that A3B nuclear import is an active process requiring at least one amino acid (Val54) within an N-terminal motif analogous to the nuclear localization determinant of the antibody gene diversification enzyme AID (activation-induced cytosine deaminase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446380", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1238, "text": "Our studies suggest that the present-day A3B enzyme retained the nuclear import mechanism of an ancestral AID protein during the expansion of the APOBEC3 locus in primates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446380", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 322, "text": "However, we found that the predominantly nuclear A3B only weakly restricted infection by HIV-1, HIV-1\u0394vif, and human T-cell leukemia virus type 1 (HTLV-1), while significantly inhibiting LINE-1 retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715505", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 887, "text": "In contrast to the exclusively cytoplasmic A3G, which is inactive against LINE-1 retrotransposition, the A3G/B protein, while localized mainly to the cytoplasm, was also present in the nucleus. Further mutational analysis revealed that residues 18, 19, 22, and 24 in A3B were the major determinants for nuclear versus cytoplasmic localization and antiretroviral activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715505", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1705, "text": "these observations suggest that changing 4 residues in the amino terminus of A3B not only retargets the protein from the nucleus to the cytoplasm but also enhances its ability to restrict HIV while retaining inhibition of retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715505", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 999, "text": "After mitosis, APOBEC3B becomes nuclear, and APOBEC3D, APOBEC3F and APOBEC3G become cytoplasmic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388464", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 508, "text": "To define the domains of APOBEC3G that determine cytoplasmic localization, comparisons were made with APOBEC3B, which is predominantly nuclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18667511", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 674, "text": "The mechanism of L1 inhibition did not correlate with an obvious subcellular protein distribution as APOBEC3B appeared predominantly nuclear and APOBEC3F was mostly cytosolic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648136", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 832, "text": "Endogenous APOBEC3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing activity in breast cancer cell-line extracts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23389445", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 673, "text": "The mechanism of L1 inhibition did not correlate with an obvious subcellular protein distribution as APOBEC3B appeared predominantly nuclear and APOBEC3F was mostly cytosolic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648136", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 507, "text": "To define the domains of APOBEC3G that determine cytoplasmic localization, comparisons were made with APOBEC3B, which is predominantly nuclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18667511", "endSection": "abstract" } ] }, { "body": "Is the regulation of Vsr endonuclease independent of the growth phase of bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10400606", "http://www.ncbi.nlm.nih.gov/pubmed/15184558", "http://www.ncbi.nlm.nih.gov/pubmed/12067333", "http://www.ncbi.nlm.nih.gov/pubmed/9537396" ], "ideal_answer": [ "The regulation of Vsr endonuclease levels is growth phase dependent." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043765", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004519" ], "type": "yesno", "id": "553fbe9fe00431e071000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Growth phase-dependent regulation of Vsr endonuclease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10400606", "endSection": "title" }, { "offsetInBeginSection": 162, "offsetInEndSection": 213, "text": "Vsr endonuclease levels are growth phase dependent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10400606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Growth phase-dependent regulation of Vsr endonuclease may contribute to 5-methylcytosine mutational hot spots in Escherichia coli.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10400606", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Using rabbit polyclonal antibodies, we have shown that the Dcm cytosine methylase of Escherichia coli is maintained at a constant level during cell growth, while Vsr endonuclease levels are growth phase dependent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10400606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Vsr endonuclease, which initiates very short patch repair, has been hypothesized to regulate mutation in stationary-phase cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9537396", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 514, "text": "The efficiency of the two pathways changes during the bacterial life cycle; MMR is more efficient during exponential growth and VSP repair is more efficient during the stationary phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12067333", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 275, "text": "Overexpression of Vsr does dramatically increase the stationary-phase reversion of a Lac- frameshift allele, but the absence of Vsr has no effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9537396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Using rabbit polyclonal antibodies, we have shown that the Dcm cytosine methylase of Escherichia coli is maintained at a constant level during cell growth, while Vsr endonuclease levels are growth phase dependent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10400606", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 513, "text": "The efficiency of the two pathways changes during the bacterial life cycle; MMR is more efficient during exponential growth and VSP repair is more efficient during the stationary phase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12067333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Vsr endonuclease, which initiates very short patch repair, has been hypothesized to regulate mutation in stationary-phase cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9537396", "endSection": "abstract" } ] }, { "body": "Are there interactomes available for POU5F1 and SOX2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23549118" ], "ideal_answer": [ "Yes. Long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) have been assayed using 4C-Seq technique. Their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/NANOG_PANTR", "http://www.uniprot.org/uniprot/NANOG_HUMAN", "http://www.uniprot.org/uniprot/PO5F1_PANTR", "http://www.uniprot.org/uniprot/NANOG_MACFA", "http://www.uniprot.org/uniprot/NANOG_MUSMM", "http://www.uniprot.org/uniprot/PO5F1_BOVIN", "http://www.uniprot.org/uniprot/PO5F1_PIG", "http://www.uniprot.org/uniprot/SOX2_DANRE", "http://www.uniprot.org/uniprot/PO5F1_MACMU", "http://www.uniprot.org/uniprot/PO5F1_DANRE", "http://www.uniprot.org/uniprot/PO5F1_HUMAN", "http://www.uniprot.org/uniprot/NANOG_BOVIN", "http://www.uniprot.org/uniprot/PO5F1_MOUSE", "http://www.uniprot.org/uniprot/SOX2_CHICK" ], "type": "yesno", "id": "56c85f675795f9a73e000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118", "endSection": "title" }, { "offsetInBeginSection": 154, "offsetInEndSection": 817, "text": "We assayed long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) using 4C-Seq technique. We discovered that their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites. In hESCs, genes within the interactomes have elevated expression. Additionally, some genes associated with the POU5F1 enhancer contribute to pluripotency. Binding sites for multiple DNA binding proteins, including ATF3, CTCF, GABPA, JUND, NANOG, RAD21 and YY1, are enriched in both interactomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23549118", "endSection": "abstract" } ] }, { "body": "Which tool is used for promoterome mining using CAGE data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25653163" ], "ideal_answer": [ "Despite their high resolution and functional significance, published CAGE data are still underused in promoter analysis due to the absence of tools that enable its efficient manipulation and integration with other genome data types. CAGEr is an R implementation of novel methods for the analysis of differential TSS usage and promoter dynamics, integrated with CAGE data processing and promoterome mining into a first comprehensive CAGE toolbox on a common analysis platform." ], "exact_answer": [ "CAGEr" ], "type": "factoid", "id": "56afe6d40a360a5e45000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "CAGEr: precise TSS data retrieval and high-resolution promoterome mining for integrative analyses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653163", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 1118, "text": " Despite their high resolution and functional significance, published CAGE data are still underused in promoter analysis due to the absence of tools that enable its efficient manipulation and integration with other genome data types. Here we present CAGEr, an R implementation of novel methods for the analysis of differential TSS usage and promoter dynamics, integrated with CAGE data processing and promoterome mining into a first comprehensive CAGE toolbox on a common analysis platform. Crucially, we provide collections of TSSs derived from most published CAGE datasets, as well as direct access to FANTOM5 resource of TSSs for numerous human and mouse cell/tissue types from within R, greatly increasing the accessibility of precise context-specific TSS data for integrative analyses. The CAGEr package is freely available from Bioconductor at http://www.bioconductor.org/packages/release/bioc/html/CAGEr.html.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653163", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 691, "text": "Here we present CAGEr, an R implementation of novel methods for the analysis of differential TSS usage and promoter dynamics, integrated with CAGE data processing and promoterome mining into a first comprehensive CAGE toolbox on a common analysis platform", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "CAGEr: precise TSS data retrieval and high-resolution promoterome mining for integrative analyses", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653163", "endSection": "title" }, { "offsetInBeginSection": 204, "offsetInEndSection": 693, "text": "Despite their high resolution and functional significance, published CAGE data are still underused in promoter analysis due to the absence of tools that enable its efficient manipulation and integration with other genome data types. Here we present CAGEr, an R implementation of novel methods for the analysis of differential TSS usage and promoter dynamics, integrated with CAGE data processing and promoterome mining into a first comprehensive CAGE toolbox on a common analysis platform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653163", "endSection": "abstract" } ] }, { "body": "Is Rheumatoid Arthritis related to myopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12682624", "http://www.ncbi.nlm.nih.gov/pubmed/19642078", "http://www.ncbi.nlm.nih.gov/pubmed/17296665", "http://www.ncbi.nlm.nih.gov/pubmed/10555889", "http://www.ncbi.nlm.nih.gov/pubmed/12652413", "http://www.ncbi.nlm.nih.gov/pubmed/15909088", "http://www.ncbi.nlm.nih.gov/pubmed/23171360" ], "ideal_answer": [ "Vacuolar myopathy and statin-induced myopathy have been reported in rheumatoid arthritis patients, but this association may be due to the anti-malarial treatment received. An increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls has been reported." ], "exact_answer": "yes", "type": "yesno", "id": "515ae990d24251bc050000ad", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19642078", "endSection": "title" }, { "offsetInBeginSection": 353, "offsetInEndSection": 475, "text": "we describe a patient with rheumatoid arthritis and respiratory failure associated with proximal myopathy secondary to HCQ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17296665", "endSection": "sections.0" }, { "offsetInBeginSection": 1, "offsetInEndSection": 108, "text": "Occurrence of chloroquine-induced myopathy after low-dose treatment of rheumatoid arthritis for seven years", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15909088", "endSection": "title" }, { "offsetInBeginSection": 488, "offsetInEndSection": 720, "text": "a 75 year old female with rheumatoid arthritis treated with daily doses of 250 mg of chloroquine for four years. The patient visited because of several months history of predominantly proximal progressive tetraparesis with areflexia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12652413", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Myopathy and neuropathy in rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10555889", "endSection": "title" }, { "offsetInBeginSection": 48, "offsetInEndSection": 153, "text": "with rheumatoid arthritis (RA) have clinical or subclinical evidence of peripheral neuropathy or myopathy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10555889", "endSection": "sections.0" }, { "offsetInBeginSection": 1321, "offsetInEndSection": 1444, "text": "The study reveals an increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10555889", "endSection": "sections.0" } ] }, { "body": "what is the role of GATA-4 in regeneration of the heart after myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22748493", "http://www.ncbi.nlm.nih.gov/pubmed/19591228", "http://www.ncbi.nlm.nih.gov/pubmed/21344679", "http://www.ncbi.nlm.nih.gov/pubmed/20870802", "http://www.ncbi.nlm.nih.gov/pubmed/22898045", "http://www.ncbi.nlm.nih.gov/pubmed/20200331", "http://www.ncbi.nlm.nih.gov/pubmed/16304579", "http://www.ncbi.nlm.nih.gov/pubmed/18290252", "http://www.ncbi.nlm.nih.gov/pubmed/15883211", "http://www.ncbi.nlm.nih.gov/pubmed/20971132" ], "ideal_answer": [ "GATA-4 is implicated in cardiogenic differentiation of cardiac c-kit+AT2+ cells that represent approximately 0.19% of total cardiac cells in infarcted heart. GATA-4 overexpression in mesenchymal stem cells increases both survival and angiogenic potential in ischemic myocardium and may therefore represent a novel and efficient therapeutic approach for postinfarct regenaration. In addition, interventions, such as hypergravity and 5-Aza treatment, induce expression of early muscle and cardiac markers like GATA-4 in BMSCs. A subpopulation of primitive cells from rat heart, expressing c-kit and myogenic transcriptional factors, GATA-4 and MEF 2C, exhibit a high in vitro proliferative potential. Progeny of these implanted cells have been shown to migrate along the infarcted scar, reconstitute regenerated cardiomyocytes with incorporation into host myocardium, and inhibit cardiac remodeling with decreased scar formation. In another study, TGF-beta has been shown to conduct the myogenic differentiation of stem cells by upregulating GATA-4 and NKx-2.5 expression and the intramyocardial implantation of TGF-beta-preprogrammed stem cells effectively assisted the myocardial regeneration. Furthermore, G-CSF treatment in postinfarcted murine hearts appears to be an effective approach for treating heart failure and also leads to induction of GATA-4 resulting in expression of various sarcomeric proteins." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050980", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ], "type": "summary", "id": "532f03e6d6d3ac6a34000022", "snippets": [ { "offsetInBeginSection": 1704, "offsetInEndSection": 2038, "text": "TGF-beta conducted the myogenic differentiation of CD117+ stem cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the intramyocardial implantation of TGF-beta-preprogrammed CD117+ cells effectively assisted the myocardial regeneration and induced therapeutic angiogenesis, contributing to functional cardiac regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15883211", "endSection": "abstract" }, { "offsetInBeginSection": 765, "offsetInEndSection": 965, "text": "G-CSF treatment also led to activation of signal transducer and activator of transcription-3 and induction of GATA-4 and various sarcomeric proteins such as myosin heavy chain, troponin I and desmin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16304579", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 1516, "text": "We describe here the identification of a subpopulation of primitive cells from rat heart, processing stem cell marker, c-kit and myogenic transcriptional factors, GATA-4 and MEF 2C, and cardiac specific proteins, troponin-I, alpha-sarcomeric actinin and connexin-43. They exhibited a high in vitro proliferative potential. These findings strongly suggest that these cells are putative cardiomyocyte precursors. After transplantation, they were able to be retained and proliferate (13.63 +/- 5.97% after 2 weeks) within the ischemic heart. Progeny of implanted cells migrated along the infarcted scar, reconstituted regenerated cardiomyocytes with incorporation into host myocardium, and inhibited cardiac remodeling with decreased scar formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18290252", "endSection": "abstract" }, { "offsetInBeginSection": 1369, "offsetInEndSection": 1822, "text": "Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of human specific alpha-cardiac actin. Human alpha cardiac actin-positive cells also expressed cardiac nuclear factors; nkx2.5 and GATA-4. Our results suggest that intracoronary artery transplantation of hCLCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22898045", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 988, "text": "This pattern of colocalization was also found in developing embryonic myocardium. Cardiac transcription factors Nkx-2.5 and GATA-4 were strongly expressed in the muscle bundles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22748493", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1318, "text": "After hypergravity and 5-Aza treatment, BMSCs showed positive for the early muscle and cardiac markers GATA-4, MEF-2, and Nkx2-5 with RT-PCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21344679", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1309, "text": "Experiments in murine models of myocardial infarction (MI) demonstrated population of VSELs expressed also early markers of cardiac and endothelial lineages (GATA-4, Nkx2.5/Csx, VE-cadherin, von Willebrand factor) which migrated to stromal-derived factor-1 (SDF-1) and other chemoattractant gradient and underwent rapid mobilization into peripheral blood in experimental MI mice models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20971132", "endSection": "abstract" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1828, "text": "We conclude that GATA-4 overexpression in MSCs increased both MSC survival and angiogenic potential in ischemic myocardium and may therefore represent a novel and efficient therapeutic approach for postinfarct remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870802", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1087, "text": "These cardiac c-kit+AT2+ cells, represented approximately 0.19% of total cardiac cells in infarcted heart, were characterized by upregulated transcription factors implicated in cardiogenic differentiation (Gata-4, Notch-2, Nkx-2.5) and genes required for self-renewal (Tbx-3, c-Myc, Akt). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19591228", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1738, "text": "these findings suggest G-CSF administration could be an effective approach to treating chronic heart failure following a large MI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16304579", "endSection": "abstract" } ] }, { "body": "What is the life expectancy of professional athletes in respect to the general population?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17849604", "http://www.ncbi.nlm.nih.gov/pubmed/8450727", "http://www.ncbi.nlm.nih.gov/pubmed/17436206", "http://www.ncbi.nlm.nih.gov/pubmed/19574095", "http://www.ncbi.nlm.nih.gov/pubmed/16389882", "http://www.ncbi.nlm.nih.gov/pubmed/9177584", "http://www.ncbi.nlm.nih.gov/pubmed/20061269", "http://www.ncbi.nlm.nih.gov/pubmed/21435018", "http://www.ncbi.nlm.nih.gov/pubmed/23450998", "http://www.ncbi.nlm.nih.gov/pubmed/8164540", "http://www.ncbi.nlm.nih.gov/pubmed/21618162", "http://www.ncbi.nlm.nih.gov/pubmed/22625998", "http://www.ncbi.nlm.nih.gov/pubmed/11761838", "http://www.ncbi.nlm.nih.gov/pubmed/17214401", "http://www.ncbi.nlm.nih.gov/pubmed/22811911", "http://www.ncbi.nlm.nih.gov/pubmed/2253729", "http://www.ncbi.nlm.nih.gov/pubmed/18369530", "http://www.ncbi.nlm.nih.gov/pubmed/23241269", "http://www.ncbi.nlm.nih.gov/pubmed/20424397", "http://www.ncbi.nlm.nih.gov/pubmed/18634917" ], "ideal_answer": [ "Elite endurance (aerobic) athletes and mixed-sports (aerobic and anaerobic) athletes show higher longevity than the general population, but results about power (anaerobic) athletes are inconsistent.", "It remains unclear if high-intensity sports activities further increase life expectancy.\nCompetitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy\nIt appears that elite endurance (aerobic) athletes and mixed-sports (aerobic and anaerobic) athletes survive longer than the general population, as indicated by lower mortality and higher longevity." ], "exact_answer": [ "longer than the general population", "No clear results indicating improved life expectancy in professional athletes" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008017", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008136" ], "type": "factoid", "id": "52e62bae98d0239505000015", "snippets": [ { "offsetInBeginSection": 1197, "offsetInEndSection": 1359, "text": "In conclusion, while regular physical activity increases life expectancy, it remains unclear if high-intensity sports activities further increase life expectancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22811911", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1458, "text": "Competitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450998", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 1039, "text": "It appears that elite endurance (aerobic) athletes and mixed-sports (aerobic and anaerobic) athletes survive longer than the general population, as indicated by lower mortality and higher longevity. Lower cardiovascular disease mortality is likely the primary reason for their better survival rates. On the other hand, there are inconsistent results among studies of power (anaerobic) athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19574095", "endSection": "abstract" } ] }, { "body": "Is EZH2 associated with prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21941025", "http://www.ncbi.nlm.nih.gov/pubmed/24375374", "http://www.ncbi.nlm.nih.gov/pubmed/23739676", "http://www.ncbi.nlm.nih.gov/pubmed/17134822", "http://www.ncbi.nlm.nih.gov/pubmed/16330673", "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "http://www.ncbi.nlm.nih.gov/pubmed/16015586", "http://www.ncbi.nlm.nih.gov/pubmed/16575874", "http://www.ncbi.nlm.nih.gov/pubmed/17914578", "http://www.ncbi.nlm.nih.gov/pubmed/17252556", "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "http://www.ncbi.nlm.nih.gov/pubmed/12734317", "http://www.ncbi.nlm.nih.gov/pubmed/18095286", "http://www.ncbi.nlm.nih.gov/pubmed/25017995", "http://www.ncbi.nlm.nih.gov/pubmed/12374981", "http://www.ncbi.nlm.nih.gov/pubmed/18637271", "http://www.ncbi.nlm.nih.gov/pubmed/21241820", "http://www.ncbi.nlm.nih.gov/pubmed/23286483", "http://www.ncbi.nlm.nih.gov/pubmed/15264237", "http://www.ncbi.nlm.nih.gov/pubmed/18159594", "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "http://www.ncbi.nlm.nih.gov/pubmed/22805308" ], "ideal_answer": [ "EZH2 is an epigenetic driver of prostate cancer. EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate cancer. EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells. EZH2 knockdown markedly reduces the proteolytic activity of MMP-9, thereby decreasing the invasive activity of prostate cancer cells. Composite index of c-Myc, EZH2, and p27 can be valued as powerful prognosis parameter for intermediate-risk prostate cancer patients after the surgery, and postoperative adjuvant therapy can be adopted accordingly." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/EZH2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011471", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011467", "http://www.disease-ontology.org/api/metadata/DOID:10286", "http://www.uniprot.org/uniprot/EZH2_MACFA" ], "type": "yesno", "id": "570908e3cf1c325851000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The role of EZH2 in the regulation of the activity of matrix metalloproteinases in prostate cancer cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "title" }, { "offsetInBeginSection": 326, "offsetInEndSection": 440, "text": "EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 618, "text": "The TIMP genes are derepressed by knockdown of EZH2 expression in human prostate cancer cells but repressed by overexpression of EZH2 in benign human prostate epithelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 802, "text": "Overexpression of EZH2 confers an invasive phenotype on benign prostate epithelial cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1004, "text": "EZH2 knockdown markedly reduces the proteolytic activity of MMP-9, thereby decreasing the invasive activity of prostate cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1257, "text": "he transcriptional repression of the TIMP genes by EZH2 may be a major mechanism to shift the MMPs/TIMPs balance in favor of MMP activity and thus to promote ECM degradation and subsequent invasion of prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 577, "text": "Expression levels of the novel tumor and metastasis suppressor Raf-1 kinase inhibitor protein (RKIP) have been shown to correlate negatively with those of EZH2 in breast and prostate cell lines as well as in clinical cancer tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Polycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP in breast and prostate cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "endSection": "title" }, { "offsetInBeginSection": 104, "offsetInEndSection": 344, "text": "Enhancer of zeste homolog 2 (EZH2), which encodes the histone methyltransferase component of the polycomb repressive complex 2 (PRC2), is overexpressed widely in breast and prostate cancers and epigenetically silences tumor suppressor genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 242, "text": "However, the roles and underlying mechanisms of EZH2 in prostate cancer stem cells (PCSCs) remain unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739676", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 257, "text": "c-Myc, EZH2 and p27 were defined to modulate the behavior of prostate cancer with pro-tumoral or anti-tumoral effects and had ability in predicting prostate cancer progression, but the research of their co-expression value of prognosis is rarely", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286483", "endSection": "abstract" }, { "offsetInBeginSection": 1875, "offsetInEndSection": 2089, "text": "Composite index of c-Myc, EZH2, and p27 can be valued as powerful prognosis parameter for intermediate-risk prostate cancer patients after the surgery, and postoperative adjuvant therapy can be adopted accordingly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "EZH2, an epigenetic driver of prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "The histone methyltransferase EZH2 has been in the limelight of the field of cancer epigenetics for a decade now since it was first discovered to exhibit an elevated expression in metastatic prostate cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 649, "text": "a comprehensive overview of EZH2 in the context of prostate cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "endSection": "title" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1066, "text": "ChIP data on prostate cancer tissue specimens and cell lines suggested EZH2 occupancy and H3K27Me3 marks on the ID4 promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1334, "text": "Collectively, our data indicate a PRC2 dependent mechanism in ID4 promoter silencing in prostate cancer through recruitment of EZH2 and a corresponding increase in H3K27Me3. Increased EZH2 but decreased ID4 expression in prostate cancer strongly supports this model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has recently attracted considerable attention because of its dysregulation in prostate cancer (PCa) and its important function in PCa development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25017995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Autoregulatory feedback loop of EZH2/miR-200c/E2F3 as a driving force for prostate cancer development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25017995", "endSection": "title" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1267, "text": "Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12374981", "endSection": "abstract" }, { "offsetInBeginSection": 1885, "offsetInEndSection": 2161, "text": "The data show that amplification of the EZH2 gene is rare in early prostate cancer, whereas a fraction of late-stage tumors contains the gene amplification leading to the overexpression of the gene, thus indicating the importance of EZH2 in the progression of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575874", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 575, "text": "EZH2 expression in prostate cancer correlates with progression to hormone-refractory and metastatic disease, but it is unknown whether EZH2 plays a specific role in the acquisition of an advanced prostate cancer phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17252556", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 819, "text": "Although prior studies in prostate cancer have revealed a number of possible mechanisms of EZH2 upregulation, these changes cannot account for the overexpression EZH2 in many primary prostate cancers, nor in most cases of high grade PIN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21941025", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1021, "text": "As a result, five EZH2 peptides recognized by IgG (EZH2 120-128, EZH2 165-174, EZH2 569-577, EZH2 665-674, and EZH2 699-708) were frequently detected in the plasma of prostate cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17914578", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1460, "text": "Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12374981", "endSection": "abstract" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1764, "text": "These results link two major pathways in prostate cancer by providing two additional and complementary Myc-regulated mechanisms by which EZH2 upregulation occurs and is enforced during prostatic carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21941025", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 209, "text": "EZH2 promotes prostate cancer cell proliferation and invasiveness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18095286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "EZH2 promotes proliferation and invasiveness of prostate cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17252556", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The Polycomb Group protein EZH2 is implicated in prostate cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18095286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The polycomb group protein EZH2 is involved in progression of prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12374981", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Mutation screen and association study of EZH2 as a susceptibility gene for aggressive prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16015586", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Expression changes in EZH2, but not in BMI-1, SIRT1, DNMT1 or DNMT3B are associated with DNA methylation changes in prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18637271", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575874", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Enhancer of zeste homolog 2 (EZH2), a kind of transcriptional repressor, is reportedly over-expressed in metastatic prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18159594", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 629, "text": "IgGs reactive to three EZH2 peptides (EZH2-243 to -252, EZH2-291 to -299, and EZH2-735 to -;742) were detected in the plasma of almost half of prostate cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15264237", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1058, "text": "Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12374981", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 443, "text": "Overexpression of EZH2 has been associated with the invasion and progression of malignant cancers, especially with the progression of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21241820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Antigens overexpressed in metastatic prostate cancer are appropriate targets in anti-cancer immunotherapy, and one candidate is the polycomb group protein enhancer of zeste homolog 2 (EZH2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15264237", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 900, "text": " Cytoplasmic EZH2 is expressed at low levels in benign prostate epithelial cells and over-expressed in prostate cancer cells. Cytoplasmic EZH2 expression levels correlate with nuclear EZH2 expression in prostate cancer samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18095286", "endSection": "abstract" }, { "offsetInBeginSection": 53, "offsetInEndSection": 132, "text": "DNMT1 or DNMT3B are associated with DNA methylation changes in prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18637271", "endSection": "title" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1483, "text": "EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12734317", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1329, "text": "a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12734317", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1447, "text": "PcG proteins EZH2, BMI1, and RING1 are associated with adverse pathologic features and clinical PSA recurrence of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17134822", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 909, "text": "Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12734317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Elevation of the chromatin repression factor enhancer of zeste homolog (EZH2) is associated with progression and poor prognosis in several human cancers including prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22805308", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 278, "text": "Various proteins (\u03b12-integrin, \u03b16-integrin, CD117, CD133, EZH2, OCT3/4) are associated with a prostate cancer stem cell phenotype in cell lines and xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24375374", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 233, "text": "Increased expression of EZH2 has been associated previously with invasive growth and aggressive clinical behavior in prostate and breast cancer,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16330673", "endSection": "abstract" }, { "offsetInBeginSection": 1942, "offsetInEndSection": 2123, "text": "EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence after radical prostatectomy and may be useful in defining a cohort of high-risk patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12734317", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 990, "text": "Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12734317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16330673", "endSection": "title" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1329, "text": "Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12734317", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 900, "text": "Cytoplasmic EZH2 expression levels correlate with nuclear EZH2 expression in prostate cancer samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18095286", "endSection": "abstract" } ] }, { "body": "How does adrenergic signaling affect thyroid hormone receptors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18622044" ], "ideal_answer": [ "alpha1- adrenergic signalling increases TRalpha1 expression in nucleus and decreases TRalpha1 expression in cytosol." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/THB_MOUSE", "http://www.uniprot.org/uniprot/THA_SHEEP" ], "type": "summary", "id": "516d5bdf298dcd4e5100007a", "snippets": [ { "offsetInBeginSection": 791, "offsetInEndSection": 945, "text": "PE, in the absence of T3, resulted in 5.0 fold increase in TRalpha1 expression in nucleus and 2.0 fold decrease in TRalpha1 expression in cytosol, P<0.05.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18622044", "endSection": "sections.0" }, { "offsetInBeginSection": 1600, "offsetInEndSection": 1763, "text": "nuclear TRalpha1 is overexpressed after prolonged activation of the alpha1- adrenergic signalling by PE. This response seems to be an ERK kinase dependent process.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18622044", "endSection": "sections.0" } ] }, { "body": "What are the computational tools for the prediction of beta-barrel transmembrane proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15647112", "http://www.ncbi.nlm.nih.gov/pubmed/16844989", "http://www.ncbi.nlm.nih.gov/pubmed/16844988", "http://www.ncbi.nlm.nih.gov/pubmed/15980447", "http://www.ncbi.nlm.nih.gov/pubmed/18434251", "http://www.ncbi.nlm.nih.gov/pubmed/17597890", "http://www.ncbi.nlm.nih.gov/pubmed/21328706", "http://www.ncbi.nlm.nih.gov/pubmed/20952406", "http://www.ncbi.nlm.nih.gov/pubmed/23297037", "http://www.ncbi.nlm.nih.gov/pubmed/22540951", "http://www.ncbi.nlm.nih.gov/pubmed/18989393", "http://www.ncbi.nlm.nih.gov/pubmed/18006547", "http://www.ncbi.nlm.nih.gov/pubmed/21426944", "http://www.ncbi.nlm.nih.gov/pubmed/12169530", "http://www.ncbi.nlm.nih.gov/pubmed/18783592", "http://www.ncbi.nlm.nih.gov/pubmed/15141026", "http://www.ncbi.nlm.nih.gov/pubmed/15980452", "http://www.ncbi.nlm.nih.gov/pubmed/18467177", "http://www.ncbi.nlm.nih.gov/pubmed/19421989", "http://www.ncbi.nlm.nih.gov/pubmed/22987359", "http://www.ncbi.nlm.nih.gov/pubmed/15070403", "http://www.ncbi.nlm.nih.gov/pubmed/17597895", "http://www.ncbi.nlm.nih.gov/pubmed/15769290", "http://www.ncbi.nlm.nih.gov/pubmed/16351738", "http://www.ncbi.nlm.nih.gov/pubmed/15215418", "http://www.ncbi.nlm.nih.gov/pubmed/15215419", "http://www.ncbi.nlm.nih.gov/pubmed/16225682", "http://www.ncbi.nlm.nih.gov/pubmed/15261149", "http://www.ncbi.nlm.nih.gov/pubmed/23555228", "http://www.ncbi.nlm.nih.gov/pubmed/16542876", "http://www.ncbi.nlm.nih.gov/pubmed/16597327", "http://www.ncbi.nlm.nih.gov/pubmed/17557332", "http://www.ncbi.nlm.nih.gov/pubmed/22247276", "http://www.ncbi.nlm.nih.gov/pubmed/17958348" ], "ideal_answer": [ "The computational tools for the prediction of beta-barrel transmembrane proteins (TMBs) are based mainly on the following methodologies: Hidden Markov Models (HMMs), hydrophobicity, structural data, k-nearest neighbor algorithm, Neural Networks and Support Vector Machines. The state-of-the-art computational tools for the prediction of TMBs are: BETAWARE, BOCTOPUS, BOMP, BTMX, HMM-B2TMR, OMPdb,PRED-TMBB, PROB, ProfTMB, PV, TMBETA-NET, TMB finding pipeline, TMBETADISC-RBF, TMBETAPRED-RBF, TMBHMM, TMB-Hunt, TMB-Hunt2, TMBKNN, TMBpro, transFold." ], "exact_answer": [ [ "BETAWARE" ], [ "BOCTOPUS" ], [ "BOMP" ], [ "BTMX" ], [ "HMM-B2TMR" ], [ "OMPdb" ], [ "PRED-TMBB" ], [ "PROB" ], [ "ProfTMB" ], [ "PV" ], [ "TMB finding pipeline" ], [ "TMBETADISC-RBF" ], [ "TMBETAPRED-RBF" ], [ "TMBHMM" ], [ "TMB-Hunt", "TMB-Hunt2" ], [ "TMBKNN" ], [ "TMBpro" ], [ "transFold" ], [ "TMBETA-NET" ] ], "type": "list", "id": "51434c74d24251bc0500000c", "snippets": [ { "offsetInBeginSection": 168, "offsetInEndSection": 332, "text": "In this work, we propose a method based on radial basis networks for predicting the number of beta-strands in OMPs and identifying their membrane spanning segments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989", "endSection": "sections.0" }, { "offsetInBeginSection": 624, "offsetInEndSection": 806, "text": "We have developed a web server, TMBETAPRED-RBF for predicting the transmembrane beta-strands from amino acid sequence and it is available at http://rbf.bioinfo.tw/~sachen/tmrbf.html.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19421989", "endSection": "sections.0" }, { "offsetInBeginSection": 1044, "offsetInEndSection": 1160, "text": "We have developed a prediction server, TMBETADISC-RBF, which is available at http://rbf.bioinfo.tw/~sachen/OMP.html.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434251", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "TMB finding pipeline: novel approach for detecting beta-barrel membrane proteins in genomic sequences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17958348", "endSection": "title" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1235, "text": "Interestingly, the present approach identified TMBs from all 15 families in TCDB.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17958348", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "A new method is presented for identification of beta-barrel membrane proteins. It is based on a hidden Markov model (HMM) with an architecture obeying these proteins' construction principles. Once the HMM is trained, log-odds score relative to a null model is used to discriminate beta-barrel membrane proteins from other proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15261149", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "PRED-TMBB: a web server for predicting the topology of beta-barrel outer membrane proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215419", "endSection": "title" }, { "offsetInBeginSection": 346, "offsetInEndSection": 684, "text": "We present here a web server (PRED-TMBB, http://bioinformatics.biol.uoa.gr/PRED-TMBB) which is capable of predicting the transmembrane strands and the topology of beta-barrel outer membrane proteins of Gram-negative bacteria. The method is based on a Hidden Markov Model, trained according to the Conditional Maximum Likelihood criterion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215419", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Predicting transmembrane beta-barrels in proteomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026", "endSection": "title" }, { "offsetInBeginSection": 241, "offsetInEndSection": 386, "text": "Here we introduced the design, statistics and results of a novel profile-based hidden Markov model for the prediction and discrimination of TMBs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15141026", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "A sequence-profile-based HMM for predicting and discriminating beta barrel membrane proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12169530", "endSection": "title" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1133, "text": "RESULTS: We develop a HMM model, which can predict the topology of beta barrel membrane proteins using, as input, evolutionary information.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12169530", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "BOMP: a program to predict integral beta-barrel outer membrane proteins encoded within genomes of Gram-negative bacteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215418", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "This work describes the development of a program that predicts whether or not a polypeptide sequence from a Gram-negative bacterium is an integral beta-barrel outer membrane protein. The program, called the beta-barrel Outer Membrane protein Predictor (BOMP), is based on two separate components to recognize integral beta-barrel proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215418", "endSection": "sections.0" }, { "offsetInBeginSection": 139, "offsetInEndSection": 432, "text": "On the basis of existing knowledge of beta-barrel outer-membrane proteins, several state of the art prediction methods, as well as a new in-house program (PROB) were employed for the systematic exploration of Mycobacterium tuberculosis predicted proteomes for potential beta-barrel structures.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16542876", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Computational identification of beta-barrel outer-membrane proteins in Mycobacterium tuberculosis predicted proteomes as putative vaccine candidates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16542876", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "BETAWARE: a machine-learning tool to detect and predict transmembrane beta-barrel proteins in prokaryotes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037", "endSection": "title" }, { "offsetInBeginSection": 684, "offsetInEndSection": 866, "text": "Recently, we developed two top-performing methods based on machine-learning approaches to tackle both the detection of TMBBs in sets of proteins and the prediction of their topology.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23297037", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Supersecondary structure prediction of transmembrane beta-barrel proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987359", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "We introduce a graph-theoretic model for predicting the supersecondary structure of transmembrane \u03b2-barrel proteins--a particular class of proteins that performs diverse important functions but it is difficult to determine their structure with experimental methods.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987359", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "BOCTOPUS: improved topology prediction of transmembrane \u03b2 barrel proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247276", "endSection": "title" }, { "offsetInBeginSection": 480, "offsetInEndSection": 655, "text": "Here, we present BOCTOPUS; an improved method for the topology prediction of TMBs by employing a combination of support vector machines (SVMs) and Hidden Markov Models (HMMs).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247276", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "TMBHMM: a frequency profile based HMM for predicting the topology of transmembrane beta barrel proteins and the exposure status of transmembrane residues.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 838, "text": "We present here TMBHMM, a computational method based on a hidden Markov model for predicting the structural topology of putative TMBs from sequence. In addition to predicting transmembrane strands, TMBHMM also predicts the exposure status (i.e., exposed to the membrane or hidden in the protein structure) of the residues in the transmembrane region, which is a novel feature of the TMBHMM method. Furthermore, TMBHMM can also predict the membrane residues that are not part of beta barrel forming strands.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21426944", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "We present BTMX (Beta barrel TransMembrane eXposure), a computational method to predict the exposure status (i.e. exposed to the bilayer or hidden in the protein structure) of transmembrane residues in transmembrane beta barrel proteins (TMBs). BTMX predicts the exposure status of known TM residues with an accuracy of 84.2% over 2,225 residues and provides a confidence score for all predictions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21328706", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A method for discovering transmembrane beta-barrel proteins in Gram-negative bacterial proteomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467177", "endSection": "title" }, { "offsetInBeginSection": 570, "offsetInEndSection": 682, "text": "A web server based on the proposed method is available at http://yanbioinformatics.cs.usu.edu:8080/TMBKNNsubmit.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467177", "endSection": "sections.0" }, { "offsetInBeginSection": 100, "offsetInEndSection": 199, "text": "This paper presents a k-nearest neighbor (K-NN) method for discriminating TMB and non-TMB proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467177", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "TMBpro: secondary structure, beta-contact and tertiary structure prediction of transmembrane beta-barrel proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006547", "endSection": "title" }, { "offsetInBeginSection": 732, "offsetInEndSection": 1102, "text": "We develop a suite (TMBpro) of specialized predictors for predicting secondary structure (TMBpro-SS), beta-contacts (TMBpro-CON) and tertiary structure (TMBpro-3D) of transmembrane beta-barrel proteins. We compare our results to the recent state-of-the-art predictors transFold and PRED-TMBB using their respective benchmark datasets, and leave-one-out cross-validation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18006547", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A consensus algorithm to screen genomes for novel families of transmembrane beta barrel proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17557332", "endSection": "title" }, { "offsetInBeginSection": 554, "offsetInEndSection": 769, "text": "Here we describe a new algorithm combining composition and hidden Markov model topology based classifiers (called TMB-Hunt2), which achieves a crossvalidation accuracy of >95%, with 96.7% precision and 94.2% recall.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17557332", "endSection": "sections.0" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1476, "text": "Tools and datasets are made available through a website called TMB-Web (http://www.bioinformatics.leeds.ac.uk/TMB-Web/TMB-Hunt2).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17557332", "endSection": "sections.0" } ] }, { "body": "Which kinase is regulating stress granule biogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25840010" ], "ideal_answer": [ "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis", "Multiple lines of evidence define the master metabolic regulator 5'-AMP-activated protein kinase alpha (AMPK-alpha) as a novel component of stress granules (SGs) that also controls their biogenesis." ], "type": "summary", "id": "56cdf4675795f9a73e00003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "title" }, { "offsetInBeginSection": 645, "offsetInEndSection": 1162, "text": "Multiple lines of evidence link AMPK activity to SG biogenesis. First, pharmacological kinase inhibition interfered with SG formation. Second, AMPK-\u03b1 knockdown combined with in-depth quantitative SG analysis revealed isoform-specific changes of SG characteristics. Third, overexpression of mutant \u03b1-subunits further substantiated that AMPK regulates SG parameters. Finally, we identified the SG-nucleating protein G3BP1 as an AMPK-\u03b12 binding partner. This interaction is stimulated by stress and notably occurs in SGs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1291, "text": "our data define the master metabolic regulator AMPK as a novel SG constituent that also controls their biogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "title" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1292, "text": "Collectively, our data define the master metabolic regulator AMPK as a novel SG constituent that also controls their biogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1292, "text": "This interaction is stimulated by stress and notably occurs in SGs. Collectively, our data define the master metabolic regulator AMPK as a novel SG constituent that also controls their biogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis..", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "title" } ] }, { "body": "What is the association between cell phone use and glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24348390", "http://www.ncbi.nlm.nih.gov/pubmed/24064953", "http://www.ncbi.nlm.nih.gov/pubmed/19261451", "http://www.ncbi.nlm.nih.gov/pubmed/20215713", "http://www.ncbi.nlm.nih.gov/pubmed/16804530", "http://www.ncbi.nlm.nih.gov/pubmed/18941554", "http://www.ncbi.nlm.nih.gov/pubmed/16570042", "http://www.ncbi.nlm.nih.gov/pubmed/23261330", "http://www.ncbi.nlm.nih.gov/pubmed/22882019", "http://www.ncbi.nlm.nih.gov/pubmed/10375602", "http://www.ncbi.nlm.nih.gov/pubmed/19494549", "http://www.ncbi.nlm.nih.gov/pubmed/19126439", "http://www.ncbi.nlm.nih.gov/pubmed/17902192", "http://www.ncbi.nlm.nih.gov/pubmed/14648713", "http://www.ncbi.nlm.nih.gov/pubmed/12527940", "http://www.ncbi.nlm.nih.gov/pubmed/17851009", "http://www.ncbi.nlm.nih.gov/pubmed/23095687" ], "ideal_answer": [ "The association between cell phone use and incident glioblastoma remains unclear. Some studies have reported that cell phone use was associated with incident glioblastoma, and with reduced survival of patients diagnosed with glioblastoma. However, other studies have repeatedly replicated to find an association between cell phone use and glioblastoma." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005909", "http://www.disease-ontology.org/api/metadata/DOID:3073", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040421" ], "type": "summary", "id": "530e1b205937551c09000003", "snippets": [ { "offsetInBeginSection": 946, "offsetInEndSection": 1050, "text": "Decreased survival of glioma cases with long-term and high cumulative use of wireless phones was found. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095687", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1362, "text": "There was no significant association between glioma and alcohol consumption, smoking and mobile phone use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19494549", "endSection": "abstract" }, { "offsetInBeginSection": 1585, "offsetInEndSection": 2049, "text": "Regular cell phone use was not associated with an increased risk of neuroma (OR=0,92; 95% confidence interval=[0.53-1.59]), meningioma (OR=0,74; 95% confidence interval=[0.43-1.28]) or glioma (OR=1.15; 95% confidence interval=[0.65-2.05]). Although these results are not statistically significant, a general tendency was observed for an increased risk of glioma among the heaviest users: long-term users, heavy users, users with the largest numbers of telephones. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17851009", "endSection": "abstract" }, { "offsetInBeginSection": 2061, "offsetInEndSection": 2190, "text": "No significant increased risk for glioma, meningioma or neuroma was observed among cell phone users participating in Interphone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17851009", "endSection": "abstract" }, { "offsetInBeginSection": 2245, "offsetInEndSection": 2404, "text": " Our results, suggesting the possibility of an increased risk among the heaviest users, therefore need to be verified in the international INTERPHONE analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17851009", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1139, "text": "The risk for ipsilateral use was significantly increased for astrocytoma for all studied phone types, analogue phones OR=1.8,95% CI=1.1-3.2, digital phones OR=1.8, 95% CI=1.1-2.8, cordless phones OR=1.8, 95% CI=1.1-2.9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12527940", "endSection": "abstract" }, { "offsetInBeginSection": 1801, "offsetInEndSection": 2152, "text": "For astrocytoma and ipsilateral use the trend was for analogue phones OR=1.10, 95% CI=1.02-1.19, digital phones OR=1.11, 95% CI=1.01-1.22, and cordless phones OR=1.09, 95% CI=1.01-1.19. There was a tendency of a shorter tumour induction period for ipsilateral exposure to microwaves than for contralateral, which may indicate a tumour promotor effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12527940", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 353, "text": "Case reports of brain tumours in users initiated this case-control study on brain tumours and use of cellular telephones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10375602", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1498, "text": "Increased risk was found only for use of the NMT system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10375602", "endSection": "abstract" }, { "offsetInBeginSection": 1696, "offsetInEndSection": 1790, "text": "This increased HR was based on results for astrocytoma WHO grade IV (glioblastoma multiforme).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261330", "endSection": "abstract" }, { "offsetInBeginSection": 1994, "offsetInEndSection": 2079, "text": "Some studies show increasing incidence of brain tumours whereas other studies do not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261330", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1103, "text": "The meta-analysis gave for glioma in the most exposed part of the brain, the temporal lobe, odds ratio (OR)=1.71, 95% confidence interval (CI)=1.04-2.81 in the \u226510 years (>10 years in the Hardell group) latency group. Ipsilateral mobile phone use \u22651640h in total gave OR=2.29, 95% CI=1.56-3.37. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261330", "endSection": "abstract" }, { "offsetInBeginSection": 1427, "offsetInEndSection": 1578, "text": "After 1983 and during the period with increasing prevalence of mobile phone users, the incidence has remained relatively stable for both men and women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14648713", "endSection": "abstract" } ] }, { "body": "Is there any cross-talk between the Wnt and the Akt pathways?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22337886", "http://www.ncbi.nlm.nih.gov/pubmed/19158508", "http://www.ncbi.nlm.nih.gov/pubmed/19850932", "http://www.ncbi.nlm.nih.gov/pubmed/19887570", "http://www.ncbi.nlm.nih.gov/pubmed/20888802", "http://www.ncbi.nlm.nih.gov/pubmed/15537647", "http://www.ncbi.nlm.nih.gov/pubmed/23776620", "http://www.ncbi.nlm.nih.gov/pubmed/23646150", "http://www.ncbi.nlm.nih.gov/pubmed/17896924", "http://www.ncbi.nlm.nih.gov/pubmed/16940750", "http://www.ncbi.nlm.nih.gov/pubmed/18687666", "http://www.ncbi.nlm.nih.gov/pubmed/11782444", "http://www.ncbi.nlm.nih.gov/pubmed/23657601", "http://www.ncbi.nlm.nih.gov/pubmed/20028853", "http://www.ncbi.nlm.nih.gov/pubmed/15655376" ], "ideal_answer": [ "The Wnt/\u03b2-catenin and PI3K/Akt signaling pathways cross-talk mainly through the activity of GSK-3\u03b2, a common component of both pathways, but also through the activity of other signaling transducers, such as Cby or WISP-1." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020239", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030111", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043491", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060070", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060828", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051896", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043422", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051057", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051155", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060449", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060490", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051153" ], "type": "yesno", "id": "5319a7b2b166e2b806000028", "snippets": [ { "offsetInBeginSection": 1593, "offsetInEndSection": 1926, "text": "Our data demonstrate that engaging Wnt signaling at the receptor level by this method leads to necessary crosstalk between multiple signaling pathways including activation of Akt, mTOR, Wnt/\u03b2-catenin, PKA/CREB, and inhibition of RhoA/ROCK that substantially increase human \u03b2-cell proliferation while maintaining the \u03b2-cell phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23776620", "endSection": "abstract" }, { "offsetInBeginSection": 1665, "offsetInEndSection": 1862, "text": "The cross-talk role of Wnt/\u03b2-catenin and PI3K/Akt signaling pathway, with GSK-3\u03b2 as the key enzyme bridging these pathways, may contribute to the inhibition of cholangiocarcinoma cells by hUC-MSCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23646150", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 577, "text": "We find that Wnt stimulation leads to phosphorylation of insulin signaling key mediators, including Akt, GSK3\u03b2, and ERK1/2, although with a lower fold stimulation and slower time course than observed for insulin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22337886", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1233, "text": "Wnt induces phosphorylation of Akt, ERK1/2, and GSK3\u03b2, and this is dependent on insulin/IGF-1 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22337886", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 622, "text": "Pharmacologic inhibition of PI3K resulted in the downregulation of several members of the \u03b2-catenin pathway, including Fra-1, c-Myc, and cyclin D1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20888802", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 1004, "text": "Similar results were observed in vivo, as intratumoral injection of LY294002 downregulated the expression of the components of the \u03b2-catenin pathway and delayed tumor growth in nude mice harboring subcutaneous LN229 xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20888802", "endSection": "abstract" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1152, "text": "These results suggest that the PI3K/AKT signaling pathway regulates glioma cell proliferation, in part via repression of the Wnt/\u03b2-catenin pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20888802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20028853", "endSection": "title" }, { "offsetInBeginSection": 585, "offsetInEndSection": 850, "text": "Small-molecule inhibitors targeting the PI3K/Akt signaling pathway affected beta-catenin signaling by activation [corrected] of GSK-3beta, [corrected] resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20028853", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1468, "text": "These findings demonstrate the importance of cross-talk between the PI3K/Akt and beta-catenin pathways in medulloblastoma and rationalize the PI3K/Akt signaling pathway as a therapeutic target in treatment of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20028853", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 853, "text": "Western blot analyses revealed that the recombinant Wnt ligand Wnt-3A increased phosphorylation of AKT and the downstream kinase glycogen synthase kinase (GSK)-3beta as well as accumulation of activated, nuclear beta-catenin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887570", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1223, "text": "Chemical inhibition of PI3K abolished Wnt-dependent phosphorylation of AKT and GSK-3beta and trophoblast motility but did not affect appearance of activated beta-catenin or Wnt/TCF reporter activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887570", "endSection": "abstract" }, { "offsetInBeginSection": 1574, "offsetInEndSection": 1680, "text": "The data suggest that Wnt-3A may activate canonical Wnt signaling and PI3K/AKT through distinct receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "Mutational activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in a wide variety of tumors, whereas activating Wnt pathway mutants are predominantly found in colon cancer. Because GSK3 is a key component of both pathways, it is widely assumed that active PI3K signaling feeds positively into the Wnt pathway by protein kinase B (PKB)-mediatefd inhibition of GSK3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19850932", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 527, "text": "n addition, PKB has been proposed to modulate the canonical Wnt signaling through direct stabilization and nuclear localization of beta-catenin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19850932", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 741, "text": "Here, we show that compartmentalization by Axin of GSK3 prohibits cross-talk between the PI3K and Wnt pathways and that Wnt-mediated transcriptional activity is not modulated by activation of the PI3K/PKB pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19850932", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 605, "text": "Our recent study revealed a second mechanism for Cby-mediated beta-catenin inhibition in which Cby cooperates with 14-3-3 adaptor proteins to facilitate nuclear export of beta-catenin, following phosphorylation of Cby by Akt kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19158508", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 824, "text": "Therefore, our findings unravel a novel molecular mechanism regulating the dynamic nucleo-cytoplasmic trafficking of beta-catenin and provide new insights into the cross-talk between the Wnt and Akt signaling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19158508", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 971, "text": "Here, we review recent literature concerning Cby function and discuss our current understanding of the relationship between Wnt and Akt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19158508", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1355, "text": "As inappropriate activation of WNT/CTNNB1 signaling causes late-onset GCT development and cross talk between the PI3K/AKT and WNT/CTNNB1 pathways has been reported, we tested whether these pathways could synergize in GCT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687666", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1354, "text": "This explains why prostate tumors subjected to androgen ablation experience an increase in Akt phosphorylation, and suggest that the tumor compensates for the loss of one pathway with another. Different modes of interaction between the two pathways, including direct interaction, or regulation via downstream intermediates, such as the wnt/GSK-3beta/beta-catenin pathway, NF-kappaB, and the FOXO family of transcription factors, will be discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17896924", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 870, "text": "FGF signals are transduced through FGF receptor to the FRS2-GRB2-GAB1-PI3K-AKT signaling cascade to downregulate GSK3beta activity depending on Ser 9 phosphorylation. Because GSK3beta-dependent phosphorylation of beta-catenin and SNAIL leads to FBXW1 (betaTRCP)-mediated ubiquitination and degradation, GSK3beta downregulation results in the stabilization and the nuclear accumulation of beta-catenin and SNAIL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Bridging the BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3zeta", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15655376", "endSection": "title" }, { "offsetInBeginSection": 633, "offsetInEndSection": 858, "text": "Concurrently, PTEN, an inhibitor of PI3K/Akt pathway, is also primarily inactivated in the ISCs, leading to activation of Akt. Thus, Akt may contribute to activation of beta-catenin in ISCs in coordination with Wnt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15655376", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1346, "text": "Thus, we propose that BMP signaling plays a role in inhibition of ISC self-renewal through suppression of Wnt/beta-catenin signaling in ISC, and this cross-talk is bridged, at least in part, through the PTEN/Akt pathway and further enforced by 14-3-3zeta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15655376", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 324, "text": "In MC3T3-E1 osteoblast-like cultures, dexamethasone (DEX) activates glycogen synthase kinase-3beta (GSK3beta) and inhibits a differentiation-related cell cycle that occurs at a commitment stage immediately after confluence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15537647", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 502, "text": "Here we show that DEX inhibition of the differentiation-related cell cycle is associated with a decrease in beta-catenin levels and inhibition of LEF/TCF-mediated transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15537647", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 603, "text": "These inhibitory activities are no longer observed in the presence of lithium, a GSK3beta inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15537647", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 885, "text": "DEX decreased the serum-responsive phosphorylation of protein kinase B/Akt-Ser(473) within minutes, and this inhibition was also observed after 12 h. When the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was inhibited by wortmannin, DEX no longer inhibited beta-catenin levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15537647", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1138, "text": "Furthermore, DEX-mediated inhibition of LEF/TCF transcriptional activity was attenuated in the presence of dominant negative forms of either PI3K or protein kinase B/Akt. These results suggest cross-talk between the PI3K/Akt and Wnt signaling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15537647", "endSection": "abstract" }, { "offsetInBeginSection": 1805, "offsetInEndSection": 2034, "text": "These results suggest that inhibition of a PI3K/Akt/GSK3beta/beta-catenin/LEF axis and stimulation of HDAC1 cooperate to mediate the inhibitory effect of DEX on Wnt signaling and the osteoblast differentiation-related cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15537647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11782444", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 478, "text": "Here it is shown that WISP-1 can activate the antiapoptotic Akt/PKB signaling pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11782444", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1122, "text": "Our results show that both TGF\u03b21 and Wnt3a lead to increased accumulation of \u03b2-catenin, phosphorylation of AKT and p44/42 MAPK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23657601", "endSection": "abstract" } ] }, { "body": "Has the protein GFP been used in transgenesis for live protein imaging?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23480392", "http://www.ncbi.nlm.nih.gov/pubmed/21708138", "http://www.ncbi.nlm.nih.gov/pubmed/22497513", "http://www.ncbi.nlm.nih.gov/pubmed/24312079", "http://www.ncbi.nlm.nih.gov/pubmed/20378924", "http://www.ncbi.nlm.nih.gov/pubmed/21248708", "http://www.ncbi.nlm.nih.gov/pubmed/24297703", "http://www.ncbi.nlm.nih.gov/pubmed/19087237", "http://www.ncbi.nlm.nih.gov/pubmed/20085825", "http://www.ncbi.nlm.nih.gov/pubmed/22700411", "http://www.ncbi.nlm.nih.gov/pubmed/22173943", "http://www.ncbi.nlm.nih.gov/pubmed/22551423", "http://www.ncbi.nlm.nih.gov/pubmed/22493255", "http://www.ncbi.nlm.nih.gov/pubmed/19688097", "http://www.ncbi.nlm.nih.gov/pubmed/20226563", "http://www.ncbi.nlm.nih.gov/pubmed/21316751", "http://www.ncbi.nlm.nih.gov/pubmed/21490567", "http://www.ncbi.nlm.nih.gov/pubmed/19549299", "http://www.ncbi.nlm.nih.gov/pubmed/21406720" ], "ideal_answer": [ "Yes, the stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019076", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030781", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000818", "http://www.uniprot.org/uniprot/GFP_AEQVI", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030801" ], "type": "yesno", "id": "5523e8cc7b523f2123000007", "snippets": [ { "offsetInBeginSection": 423, "offsetInEndSection": 638, "text": "we review recent advancement in the functional studies of the three different GnRH neuron systems, mainly focusing on the electrophysiological analysis of the GnRH-green fluorescent protein (GFP) transgenic animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24312079", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 681, "text": "founders were found to be transgenic for GFP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297703", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 906, "text": "GFP expression was detected in a wide range of murine tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Transgenic Xenopus laevis for live imaging in cell and developmental biology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23480392", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23480392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "GFP-transgenic animals for in vivo imaging: rats, rabbits, and pigs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22700411", "endSection": "title" }, { "offsetInBeginSection": 482, "offsetInEndSection": 627, "text": "We have further extended the techniques of genetic engineering to rats, rabbits, and pigs, and have created corresponding GFP-transgenic animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22700411", "endSection": "abstract" }, { "offsetInBeginSection": 1473, "offsetInEndSection": 1661, "text": "The results revealed that the 3.6-GFP transgenic animals provide a unique model for direct analysis of cellular and molecular mechanisms of pulp repair and tertiary dentinogenesis in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22551423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Long-term effects of PERV-specific RNA interference in transgenic pigs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22497513", "endSection": "title" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1319, "text": "green fluorescent protein (GFP) as reporter of the vector system were consistently expressed in transgenic animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22497513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The ability to specify the expression levels of exogenous genes inserted in the genomes of transgenic animals is critical for the success of a wide variety of experimental manipulations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22493255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Welfare assessment in transgenic pigs expressing green fluorescent protein (GFP).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22173943", "endSection": "title" }, { "offsetInBeginSection": 552, "offsetInEndSection": 654, "text": "transgenic animals expressing GFP with wildtype animals along various stages of post natal development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22173943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Production of transgenic chickens expressing a tetracycline-inducible GFP gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21708138", "endSection": "title" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1116, "text": "transgenic animals can be readily created to express fluorescently tagged proteins or reporters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21490567", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1487, "text": "These findings suggest that mhc2dab:GFP and cd45:DsRed transgenic lines will be instrumental in elucidating the immune response in the zebrafish.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21406720", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 996, "text": "f 33 mice born, 28 (81%) carried the transgene DNA and 15 (55.5%) were GFP-positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21316751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Lentiviral vectors containing the green fluorescent protein gene have been successfully used to select transgenic embryos before transfer to a surrogate mother", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21316751", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 476, "text": "Typically transgenes are generated by placing a promoter upstream of a GFP reporter gene or cDNA of interest, and this often produces a representative expression pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21248708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Survival and immunogenicity of mesenchymal stem cells from the green fluorescent protein transgenic rat in the adult rat brain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378924", "endSection": "title" }, { "offsetInBeginSection": 166, "offsetInEndSection": 309, "text": "This problem has been lessened by the availability of transgenic animals that express \"reporter\" genes, such as green fluorescent protein (GFP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20378924", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 203, "text": " full-length GFP fusion proteins was examined, in transgenic animals, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20226563", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 734, "text": "Two stable transgenic lines express GFP prior to hair-bundle formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20085825", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 579, "text": "we generated two transgenic pigs by somatic cell nuclear transfer (SCNT) that express green fluorescent protein (GFP) driven by cytomegalovirus (CMV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19688097", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "Fluorescent proteins such as the green fluorescent protein (GFP) have widely been used in transgenic animals as reporter genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549299", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 137, "text": "Green Fluorescent Protein (GFP) is used extensively as a reporter for transgene expression in Drosophila and other organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19087237", "endSection": "abstract" } ] }, { "body": "Is the Snord116 cluster associated with the Prader-Willi syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24311433", "http://www.ncbi.nlm.nih.gov/pubmed/18320030", "http://www.ncbi.nlm.nih.gov/pubmed/22694955", "http://www.ncbi.nlm.nih.gov/pubmed/21977908", "http://www.ncbi.nlm.nih.gov/pubmed/22237428", "http://www.ncbi.nlm.nih.gov/pubmed/22495932", "http://www.ncbi.nlm.nih.gov/pubmed/20588305", "http://www.ncbi.nlm.nih.gov/pubmed/20803659", "http://www.ncbi.nlm.nih.gov/pubmed/22664655", "http://www.ncbi.nlm.nih.gov/pubmed/23686718", "http://www.ncbi.nlm.nih.gov/pubmed/23918391", "http://www.ncbi.nlm.nih.gov/pubmed/21952424", "http://www.ncbi.nlm.nih.gov/pubmed/23700380" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11940272", "o": "605436" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17465421", "o": "SNORD116-1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17460629", "o": "SMALL NUCLEOLAR RNA, C/D BOX, 116-1" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2240000", "o": "http://linkedlifedata.com/resource/umls/label/A17465421" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14199533", "o": "HBII-85-1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": 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{ "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17465421", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14199533", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14201028", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17727672", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17751406", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14203394", "o": "Metathesaurus Names" } ], "ideal_answer": [ "Yes, SNORD116 has a major role in Prader-Willi syndrome etiology." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11983", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011218" ], "type": "yesno", "id": "52b2f0d84003448f55000009", "snippets": [ { "offsetInBeginSection": 902, "offsetInEndSection": 1241, "text": "All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311433", "endSection": "abstract" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1791, "text": "These results demonstrate that the AS candidate drug topotecan acts predominantly through stabilizing R loops and chromatin decondensation at the paternally expressed PWS Snord116 locus. Our study holds promise for targeted therapies to the Snord116 locus for both AS and PWS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23700380", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 603, "text": "Recently published data strongly suggest a role for the paternally expressed small nucleolar RNA (snoRNA) cluster, SNORD116, in PWS etiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686718", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 281, "text": "Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22694955", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 668, "text": "Recent data suggest that snoRNA Snord116 is important for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia and obesity. The current study was conducted to assess a potential cellular link between Snord116 and phenotypes of PWS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "The imprinted Snurf-Snrpn chromosomal domain contains two large arrays of tandemly repeated, paternally expressed box C/D small-nucleolar RNA (snoRNA) genes: the SNORD115 (H/MBII-52) and SNORD116 (H/MBII-85) gene clusters believed to play key roles in the fine-tuning of serotonin receptor (5-HT2C) pre-mRNA processing and in the etiology of the Prader-Willi Syndrome (PWS), respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495932", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1336, "text": "There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237428", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1467, "text": "Both kits should be made available for accurate characterization of PWS/AS deletion subtypes as well as evaluating for IC and SNORD116 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21977908", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1337, "text": "There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21952424", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 377, "text": "Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20803659", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 712, "text": "In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20588305", "endSection": "abstract" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1684, "text": "Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20588305", "endSection": "abstract" } ] }, { "body": "Aleglitazar is agonist of which receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22244809", "http://www.ncbi.nlm.nih.gov/pubmed/19515415", "http://www.ncbi.nlm.nih.gov/pubmed/22113345", "http://www.ncbi.nlm.nih.gov/pubmed/21114416", "http://www.ncbi.nlm.nih.gov/pubmed/21251281", "http://www.ncbi.nlm.nih.gov/pubmed/20837369", "http://www.ncbi.nlm.nih.gov/pubmed/20336066", "http://www.ncbi.nlm.nih.gov/pubmed/24157957", "http://www.ncbi.nlm.nih.gov/pubmed/24016490", "http://www.ncbi.nlm.nih.gov/pubmed/25407798", "http://www.ncbi.nlm.nih.gov/pubmed/24682069", "http://www.ncbi.nlm.nih.gov/pubmed/22514701", "http://www.ncbi.nlm.nih.gov/pubmed/26093872" ], "ideal_answer": [ "Aleglitazar is a balanced peroxisome proliferator-activated receptor-\u03b1/\u03b3 agonist." ], "exact_answer": [ "peroxisome proliferator-activated receptor-\u03b1/\u03b3" ], "type": "factoid", "id": "56c1f00cef6e39474100003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Effects of the dual peroxisome proliferator-activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26093872", "endSection": "title" }, { "offsetInBeginSection": 142, "offsetInEndSection": 375, "text": "Aleglitazar is a dual peroxisome proliferator-activated receptor \u03b1/\u03b3 agonist with favorable insulin-sensitizing and glucose-lowering actions, favorable effects on blood lipids, and an acceptable safety profile in short-time studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26093872", "endSection": "abstract" }, { "offsetInBeginSection": 1725, "offsetInEndSection": 1891, "text": "Coupled with the previous failure of several other peroxisome proliferator-activated receptor \u03b1/\u03b3 activators, this class now holds little promise for CV therapeutics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26093872", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 308, "text": "Aleglitazar is a dual agonist of peroxisome proliferator-activated receptors with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682069", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 152, "text": "Aleglitazar acts through balanced activation of peroxisome proliferator-activated receptors \u03b1 and \u03b3; warfarin is a commonly prescribed anticoagulant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Effects of the dual peroxisome proliferator-activated receptor-\u03b1/\u03b3 agonist aleglitazar on renal function in patients with stage 3 chronic kidney disease and type 2 diabetes: a Phase IIb, randomized study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25407798", "endSection": "title" }, { "offsetInBeginSection": 155, "offsetInEndSection": 373, "text": "This Phase IIb safety study (AleNephro) in patients with stage 3 chronic kidney disease and type 2 diabetes, evaluated the renal effects of aleglitazar, a balanced peroxisome proliferator-activated receptor-\u03b1/\u03b3 agonist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25407798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Aleglitazar is a dual peroxisome proliferator-activated receptor (PPAR)-\u03b1/\u03b3 agonist in clinical development, designed to offer a balanced activation of PPAR-\u03b1 and PPAR-\u03b3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22113345", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1185, "text": "The PPARalpha- and PPARgamma-related effects occurred over similar dose ranges, indicating that aleglitazar is a balanced agonist of the two receptor subtypes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20336066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Aleglitazar is a dual peroxisome proliferator-activated receptor (PPAR)-\u03b1/\u03b3 agonist with a balanced activity (similar half-maximal effective concentrations) toward PPAR-\u03b1 and -\u03b3 that is in clinical development for the treatment of patients who have experienced an acute coronary syndrome and have type 2 diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22244809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Aleglitazar is a new, balanced dual peroxisome proliferator-activated receptor (PPAR)\u03b1/\u03b3 agonist designed to optimize lipid and glycemic benefits and minimize PPAR-related adverse effects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20837369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor \u03b1/\u03b3 agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21251281", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19515415", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Effects of the dual peroxisome proliferator-activated receptor-\u03b1/\u03b3 agonist aleglitazar on renal function in patients with stage 3 chronic kidney disease and type 2 diabetes: a Phase IIb, randomized study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25407798", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 361, "text": "Aleglitazar is a dual peroxisome proliferator-activated receptor \u03b1/\u03b3 agonist with favorable insulin-sensitizing and glucose-lowering actions, favorable effects on blood lipids, and an acceptable safety profile in short-time studies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26093872", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 408, "text": "This study was performed to evaluate the effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor \u03b1/\u03b3 (PPAR\u03b1/\u03b3) agonist, on both lipid and glycemic parameters in obese, hypertriglyceridemic, insulin-resistant rhesus monkeys", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21251281", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 361, "text": "This Phase IIb safety study (AleNephro) in patients with stage 3 chronic kidney disease and type 2 diabetes, evaluated the renal effects of aleglitazar, a balanced peroxisome proliferator-activated receptor-\u03b1/\u03b3 agonist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25407798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Evaluation of the dual peroxisome proliferator-activated receptor \ufffd/\ufffd agonist aleglitazar to reduce cardiovascular events in patients with acute coronary syndrome and type 2 diabetes mellitus: rationale and design of the AleCardio trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24016490", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19515415", "endSection": "title" }, { "offsetInBeginSection": 160, "offsetInEndSection": 667, "text": "Aleglitazar is a potent dual PPAR agonist with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles and biomarkers of cardiovascular risk. The AleCardio trial examines whether the addition of aleglitazar to standard medical therapy reduces the risk of cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome.STUDY DESIGN: AleCardio is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24016490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "To compare the molecular and biologic signatures of a balanced dual peroxisome proliferator-activated receptor (PPAR)-\u03b1/\u03b3 agonist, aleglitazar, with tesaglitazar (a dual PPAR-\u03b1/\u03b3 agonist) or a combination of pioglitazone (Pio; PPAR-\u03b3 agonist) and fenofibrate (Feno; PPAR-\u03b1 agonist) in human hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Aleglitazar, a dual PPAR-\u03b1/\u03b3 agonist, combines the lipid benefits of fibrates and the insulin-sensitizing benefits of thiazolidinediones. To investigate the pharmacokinetic effects of co-administration of atorvastatin or rosuvastatin with aleglitazar.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21114416", "endSection": "abstract" } ] }, { "body": "What are the main characteristics of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22119737", "http://www.ncbi.nlm.nih.gov/pubmed/25092222", "http://www.ncbi.nlm.nih.gov/pubmed/20517833", "http://www.ncbi.nlm.nih.gov/pubmed/22987135", "http://www.ncbi.nlm.nih.gov/pubmed/25440180", "http://www.ncbi.nlm.nih.gov/pubmed/19216760", "http://www.ncbi.nlm.nih.gov/pubmed/24025405", "http://www.ncbi.nlm.nih.gov/pubmed/25112803", "http://www.ncbi.nlm.nih.gov/pubmed/23908839" ], "ideal_answer": [ "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The phenotype of CPVT is characterized by polymorphic ventricular arrhythmias under stress and it potentially leads to syncope and/or sudden cardiac death (SCD). Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10\u2009000 and is caused by mutations in proteins controlling Ca(2+) homeostasis. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated with CPVT pathogenesis.", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10\u2009000. The genetic variants that cause CPVT are usually highly penetrant. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated with CPVT pathogenesis. Catecholaminergic polymorphic ventricular tachycardia is a malignant disease, due to mutations in proteins controlling Ca(2+) homeostasis " ], "type": "summary", "id": "54d8e319014675820d000009", "snippets": [ { "offsetInBeginSection": 29, "offsetInEndSection": 166, "text": "Catecholaminergic polymorphic ventricular tachycardia is a malignant disease, due to mutations in proteins controlling Ca(2+) homeostasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25440180", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 256, "text": "the phenotype is characterized by polymorphic ventricular arrhythmias under stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25440180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited heart rhythm disorder characterized by the occurrence of potentially life-threatening polymorphic ventricular tachyarrhythmias in conditions of physical or emotional stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25112803", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 502, "text": "CPVT is an inherited arrhythmia that is induced by physical or emotional stress and may lead to ventricular fibrillation syncope or SCD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25092222", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 340, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10\u2009000. The genetic variants that cause CPVT are usually highly penetrant. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated with CPVT pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23908839", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 327, "text": "The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23908839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Catecholaminergic polymorphic ventricular tachycardia (PCVT) is a rare, congenital ventricular tachyarrhythmia which occurs in the setting of adrenergic activation. It potentially leads to syncope and/or sudden cardiac death (SCD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "BACKGROUND: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an inherited arrhythmia syndrome, characterised by polymorphic ventricular tachycardia induced by adrenergic stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22119737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a primary electrical myocardial disease characterized by exercise- and stress-related ventricular lachycardia manifested as syncope and sudden death usually in child and teenager and was rarely described in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20517833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited cardiac disorder caused by mutations predominantly in the ryanodine receptor (RyR2) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19216760", "endSection": "abstract" } ] }, { "body": "Is poly (ADP- ribosylation) involved in transcriptional control?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1828533", "http://www.ncbi.nlm.nih.gov/pubmed/9790974", "http://www.ncbi.nlm.nih.gov/pubmed/18396434", "http://www.ncbi.nlm.nih.gov/pubmed/17158748", "http://www.ncbi.nlm.nih.gov/pubmed/17286852", "http://www.ncbi.nlm.nih.gov/pubmed/18851700" ], "ideal_answer": [ "Yes, poly (ADP- ribosylation) plays a role in the maintenance of transcriptional fidelity." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020727", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006351", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070212" ], "type": "yesno", "id": "53380000d6d3ac6a34000059", "snippets": [ { "offsetInBeginSection": 336, "offsetInEndSection": 547, "text": "Histone phosphorylation, ubiquitylation, SUMOylation and poly-ADP-ribosylation, as well as ATP-dependent nucleosome remodeling complexes, play equally pivotal roles in the maintenance of transcriptional fidelity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18851700", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 188, "text": "oly(ADP-ribose) polymerase-1 (PARP-1; EC 2.4.2.30) is an abundant nuclear protein that is involved in DNA repair, cell cycle control, programmed cell death and transcriptional regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18396434", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 213, "text": "Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17286852", "endSection": "abstract" }, { "offsetInBeginSection": 1631, "offsetInEndSection": 1765, "text": "These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17286852", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 602, "text": "PARP-1 was identified as a part of the mH2A1.1 nucleosome complex and was found to be associated with the Hsp70.1 promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158748", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1174, "text": "Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158748", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1409, "text": "Cycloheximide-induced cells were treated with two chemical inhibitors of poly(ADP-ribose) polymerase. 3-Aminobenzamide inhibited 75% of PAP gene induction and 4-hydroxyquinazolone, the highly specific inhibitor of the enzyme, blocked almost completely PAP expression, suggesting that ADP-ribosylation was indeed required for the upregulation of PAP gene expression by cycloheximide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9790974", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 589, "text": " inhibitors of poly(ADP-ribose) polymerase suppressed UV-induced HIV-1 gene expression but not tat-mediated expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1828533", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 110, "text": "oly(ADP-ribose) polymerase inhibitors suppress UV-induced human immunodeficiency virus type 1 gene expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1828533", "endSection": "title" } ] }, { "body": "Is nimodipine recommended for prevention of vasospasm in aneurysmal subarachnoid hemorrhage patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18847340", "http://www.ncbi.nlm.nih.gov/pubmed/17029347", "http://www.ncbi.nlm.nih.gov/pubmed/17705883", "http://www.ncbi.nlm.nih.gov/pubmed/22543491", "http://www.ncbi.nlm.nih.gov/pubmed/17479073", "http://www.ncbi.nlm.nih.gov/pubmed/3521193", "http://www.ncbi.nlm.nih.gov/pubmed/15846536", "http://www.ncbi.nlm.nih.gov/pubmed/19066110", "http://www.ncbi.nlm.nih.gov/pubmed/9706722", "http://www.ncbi.nlm.nih.gov/pubmed/19108757", "http://www.ncbi.nlm.nih.gov/pubmed/16998274", "http://www.ncbi.nlm.nih.gov/pubmed/21608279", "http://www.ncbi.nlm.nih.gov/pubmed/22152574", "http://www.ncbi.nlm.nih.gov/pubmed/7785750", "http://www.ncbi.nlm.nih.gov/pubmed/22027241", "http://www.ncbi.nlm.nih.gov/pubmed/18842226", "http://www.ncbi.nlm.nih.gov/pubmed/9164696" ], "ideal_answer": [ "Yes, nimodipine is recommended and FDA approved for prevention of vasospasm after aneurysmal subarachnoid hemorrhage. Multiple studies have demonstrated that nimodipine (administered orally or intravenously) is safe and effective for prevention of vasospasm, and reduce frequency of ischemic complications, lowered mortality and improved overall outcomes. Other preventive medication can be also effective for vasomotor prevention in aneurysmal subarachnoid hemorrhage patients." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020301", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011322", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013345", "http://www.disease-ontology.org/api/metadata/DOID:13100", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009553", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011315", "http://www.disease-ontology.org/api/metadata/DOID:10941", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002532", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000783" ], "type": "yesno", "id": "51490275d24251bc0500003d", "snippets": [ { "offsetInBeginSection": 643, "offsetInEndSection": 900, "text": "This article discusses some of these unresolved issues, including the use of medications such as nimodipine, antifibrinolytics, statins, and magnesium; coiling or clipping for aneurysm securement; and the prevention and treatment of potential complications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22543491", "endSection": "sections.0" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1342, "text": "The results of this study were as follows: nimodipine demonstrated benefit following aneurysmal SAH; other calcium channel blockers, including nicardipine, do not provide unequivocal benefit; triple-H therapy, fasudil, transluminal balloon angioplasty, thrombolytics, endothelin receptor antagonists, magnesium, statins, and miscellaneous therapies such as free radical scavengers and antifibrinolytics require additional study.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22152574", "endSection": "sections.0" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1316, "text": "The present results suggest that fasudil is equally or more effective than nimodipine for the prevention of cerebral vasospasm and subsequent ischemic injury in patients undergoing surgery for SAH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027241", "endSection": "sections.0" }, { "offsetInBeginSection": 1700, "offsetInEndSection": 1905, "text": "Three studies (2 meta-analyses and 1 randomized controlled trial) demonstrated that nimodipine use confers benefits (reduced morbidity and mortality) for patients with aneurysmatic subarachnoid hemorrhage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21608279", "endSection": "sections.0" }, { "offsetInBeginSection": 2246, "offsetInEndSection": 2316, "text": "Nimodipine is the only preventative treatment that can be recommended.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21608279", "endSection": "sections.0" }, { "offsetInBeginSection": 698, "offsetInEndSection": 961, "text": "Nimodipine (Nimotop), HMG Co-A reductase inhibitor (statins) and enoxaparin (Lovenox) were the only drugs with level-1 evidence available for the treatment of vasospasm from aneurysmal subarachnoid hemorrhage as defined by the US Preventative Services Task Force.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108757", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 161, "text": "The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage (SAH).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18847340", "endSection": "sections.0" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1382, "text": "There was no significant difference in the incidence of DINDs (28 vs 30% in the peroral and intravenous groups, respectively) or middle cerebral artery blood flow velocities (> 120 cm/second, 50 vs 45%, respectively).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18847340", "endSection": "sections.0" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1557, "text": "Clinical outcome according to the Glasgow Outcome Scale was the same in both groups, and there was no difference in the number of patients with new infarctions on MR imaging.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18847340", "endSection": "sections.0" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1768, "text": "The results suggest that there is no clinically relevant difference in efficacy between peroral and intravenous administration of nimodipine in preventing DINDs or cerebral vasospasm following SAH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18847340", "endSection": "sections.0" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1058, "text": "the risk of delayed cerebral ischemia is reduced with nimodipine and avoiding hypovolemia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18842226", "endSection": "sections.0" }, { "offsetInBeginSection": 470, "offsetInEndSection": 599, "text": "A recommendations (standard) for the prophylaxis and treatment of cerebral vasospasm with oral Nimodipine in good grade patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15846536", "endSection": "sections.0" }, { "offsetInBeginSection": 678, "offsetInEndSection": 1007, "text": "Of the 75 patients initially considered for active treatment, 83% underwent surgery within 48 hours of rupture, all received nimodipine, 16% received tissue plasminogen activator to lyse subarachnoid or intraventricular clots, 40% underwent hypertensive treatment, and 7% underwent transluminal balloon angioplasty for vasospasm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9706722", "endSection": "sections.0" }, { "offsetInBeginSection": 1690, "offsetInEndSection": 1850, "text": "All patients with aneurysmal SAH should be treated with the calcium antagonist nimodipine, and in certain circumstances patients should receive anticonvulsants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9164696", "endSection": "sections.0" }, { "offsetInBeginSection": 262, "offsetInEndSection": 499, "text": "The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7785750", "endSection": "sections.0" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1593, "text": "Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7785750", "endSection": "sections.0" }, { "offsetInBeginSection": 527, "offsetInEndSection": 805, "text": "In a series of 100 individuals with a ruptured supratentorial aneurysm, who were subjected to aneurysm operation in the acute stage and who subsequently received intravenous treatment with the calcium channel blocker nimodipine, the occurrence of DID with FND was reduced to 5%.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3521193", "endSection": "sections.0" }, { "offsetInBeginSection": 1382, "offsetInEndSection": 1784, "text": "There are many possible successful treatment options for preventing vasospasm, delayed ischemic neurologic deficits, and poor neurologic outcome following aneurysmal subarachnoid hemorrhage; however, further multicenter RCTs need to be performed to determine if there is a significant benefit from their use. Nimodipine is the only treatment that provided a significant benefit across multiple studies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22152574", "endSection": "sections.0" }, { "offsetInBeginSection": 641, "offsetInEndSection": 1050, "text": "Absence of symptomatic vasospasm, occurrence of low density areas associated with vasospasm on CT, and occurrence of adverse events were similar between the two groups. The clinical outcomes were more favorable in the fasudil group than in the nimodipine group (p = 0.040). The proportion of patients with good clinical outcome was 74.5% (41/55) in the fasudil group and 61.7% (37/60) in the nimodipine group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027241", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 459, "text": "Cerebral vasospasm is the classic cause of delayed neurological deterioration leading to cerebral ischemia and infarction, and thus, poor outcome and occasionally death, after aneurysmal subarachnoid hemorrhage (SAH). Advances in diagnosis and treatment, principally nimodipine, intensive care management, hemodynamic manipulations, and endovascular neuroradiology procedures, have improved the prospects for these patients, but outcomes remain disappointing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19066110", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 463, "text": "Cerebral vasospasm is the classic cause of delayed neurological deterioration after aneurysmal subarachnoid hemorrhage, leading to cerebral ischemia and infarction, and thus to poor outcome and occasionally death. Advances in diagnosis and treatment-principally the use of nimodipine, intensive care management, hemodynamic manipulations and endovascular neuroradiology procedures-have improved the prospects for these patients, but outcomes remain disappointing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17479073", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17029347", "endSection": "sections.0" }, { "offsetInBeginSection": 821, "offsetInEndSection": 873, "text": "The only proven therapy for vasospasm is nimodipine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17029347", "endSection": "sections.0" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1217, "text": "nimodipine is indicated after SAH and tirilazad is not effective.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17029347", "endSection": "sections.0" }, { "offsetInBeginSection": 643, "offsetInEndSection": 1199, "text": "Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998274", "endSection": "sections.0" } ] }, { "body": "what is the role of prostaglandins in cardiac regenaration after myocardial infarction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8782069", "http://www.ncbi.nlm.nih.gov/pubmed/20451268", "http://www.ncbi.nlm.nih.gov/pubmed/21219910" ], "ideal_answer": [ "Prostaglandins are involved in tissue regeneration after myocardial infarction and inhibitors of prostanoid production, such as aspirin and COX-2 inhibitors, have negative impact in this process. Furthermore, pharmacological interference with prostaglandin synthesis following myocardial infarction is associated with reduced fibrillar collagen formation." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011453", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ], "type": "summary", "id": "52f348542059c6d71c00000f", "snippets": [ { "offsetInBeginSection": 1141, "offsetInEndSection": 1866, "text": "This indicated different cyclooxygenase (COX)-downstream synthases and metabolizing enzymes are involved in the AA products' signaling through the COX-1 and COX-2 pathways. The presence of many enzymes' and receptors' [(COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), cytosolic prostaglandin E synthase (cPGES), prostaglandin I synthase (PGIS), the PGE(2) subtype receptors (EP(1), EP(2), and EP(4)) and the prostacyclin receptor (IP)] involvement in the prostanoid biosynthesis and activity was confirmed by western blot. The studies implied the negative effects of NSAIDs, such as aspirin and COX-2 inhibitors, which suppress prostanoid production during tissue regeneration for infarcted heart when using hESCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20451268", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1450, "text": "Thus, pharmacological interference with bradykinin-receptor binding or prostaglandin synthesis following MI is associated with reduced fibrillar collagen formation. Though the mechanism responsible for observed alteration in fibrogenesis is uncertain, anti-inflammatory and anti-proliferative properties of these agents may be responsible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8782069", "endSection": "abstract" } ] }, { "body": "What is the general function of H3K79 methylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23382701", "http://www.ncbi.nlm.nih.gov/pubmed/18003948", "http://www.ncbi.nlm.nih.gov/pubmed/21724828", "http://www.ncbi.nlm.nih.gov/pubmed/25464900", "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "http://www.ncbi.nlm.nih.gov/pubmed/24105599", "http://www.ncbi.nlm.nih.gov/pubmed/21474073", "http://www.ncbi.nlm.nih.gov/pubmed/23428873", "http://www.ncbi.nlm.nih.gov/pubmed/18977325", "http://www.ncbi.nlm.nih.gov/pubmed/24797370", "http://www.ncbi.nlm.nih.gov/pubmed/18511943", "http://www.ncbi.nlm.nih.gov/pubmed/22190683", "http://www.ncbi.nlm.nih.gov/pubmed/18285465", "http://www.ncbi.nlm.nih.gov/pubmed/21741597", "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "http://www.ncbi.nlm.nih.gov/pubmed/25417107", "http://www.ncbi.nlm.nih.gov/pubmed/17675446", "http://www.ncbi.nlm.nih.gov/pubmed/25359765" ], "ideal_answer": [ "ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. ", "ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. Conversion of H3K79 monomethylation into di- and trimethylation correlated with the transition from low- to high-level gene transcription. Findings highlight several similarities between the patterning of H3K4 methylation and that of H3K79 methylation in mammalian chromatin.\nMethylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes.", "H3K79 methylation is a histone modification that correlates with histone H4 hyperacetylation prior to histone-to-protamine transition, and is accompanied by chromatin reorganization, playing an important role in the regulation of cell proliferation." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://amigo.geneontology.org/amigo/term/GO:0032259" ], "type": "summary", "id": "56c331aa50c68dd416000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Saccharomyces cerevisiae cells lacking Dot1 exhibit a complete loss of H3K79 methylation and defects in heterochromatin-mediated silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17675446", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 933, "text": "Furthermore, an acidic patch at the C terminus of Dot1 is required for histone H4 tail binding in vitro, histone H3K79 di- and trimethylation in vivo, and proper telomere silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17675446", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 434, "text": "Recently, we demonstrated that in Drosophila spermatids, H3K79 methylation accompanies histone H4 hyperacetylation during chromatin reorganization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 972, "text": "In human and mice spermatids, di- and tri-methylated H3K79 temporally overlapped with hyperacetylated H4 and thus accompanied chromatin reorganization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "endSection": "abstract" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 1882, "text": "Our results indicated that H3K79 methylation is a histone modification conserved in Drosophila, mouse, rat and human spermatids and may be a prerequisite for proper chromatin reorganization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 740, "text": "Here, we report the cytological distribution of the evolutionarily conserved DOT1L methyltransferase and the different H3K79 methylation states resulting from its activity (mono-, di- and tri-methylation; H3K79me1, me2 and me3, respectively) during meiotic prophase I in mouse spermatocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105599", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1070, "text": "The heterochromatic centromeric regions and the sex body are enriched for H3K79me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105599", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1545, "text": "H3K79me patterns, combined with the cytological analysis of the H3.3, \u03b3H2AX, macroH2A and H2A.Z histone variants, are consistent with a differential role for these epigenetic marks in male mouse meiotic prophase I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105599", "endSection": "abstract" }, { "offsetInBeginSection": 1547, "offsetInEndSection": 1761, "text": "We propose that H3K79me2 is related to transcriptional reactivation on autosomes during pachynema, whereas H3K79me3 may contribute to the maintenance of repressive chromatin at centromeric regions and the sex body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105599", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 287, "text": "We demonstrate that H3K79 dimethylation (H3K79me2) is converted to monomethylation (H3K79me1) at HOX loci as hematopoietic cells mature, thus coinciding with a decrease in HOX gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25464900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "H3K79 methylation: a new conserved mark that accompanies H4 hyperacetylation prior to histone-to-protamine transition in Drosophila and rat", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 356, "text": "Here we show for the first time that H3K79 methylation is a conserved feature preceding the histone-to-protamine transition in Drosophila melanogaster and rat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 642, "text": "The corresponding H3K79 methylation is a histone modification that precedes the histone-to-protamine transition and correlates with histone H4 hyperacetylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1193, "text": "In rat, H3K79 methylation also correlates with H4 hyperacetylation but not with active RNA polymerase II, which might point towards a conserved function in chromatin remodeling during the histone-to-protamine transition in both Drosophila and rat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 296, "text": "Methylation of histones H3 at positions K4 and K79 is involved in the initiation of recombination and the recombination checkpoint, respectively, during meiosis in the budding yeast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24797370", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 804, "text": "We confirmed the role of Set1-dependent H3K4 methylation in the formation of double-strand breaks (DSBs) in meiosis for the initiation of meiotic recombination, and we showed the involvement of Dot1 (H3K79 methylation) in DSB formation in the absence of Set1-dependent H3K4 methylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24797370", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1103, "text": "Together, our studies identified the evolutionarily conserved YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25417107", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 693, "text": "Here, we unveil the role of Dot1-dependent histone H3 methylation at lysine 79 (H3K79me) in this meiotic surveillance mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382701", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1057, "text": "Moreover, by genetically manipulating Dot1 catalytic activity, we find that the status of H3K79me modulates the meiotic checkpoint response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Methylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23428873", "endSection": "abstract" }, { "offsetInBeginSection": 1262, "offsetInEndSection": 1448, "text": "Thus, H3K79 methylation is not essential for transcription of Wnt-responsive or other intestinal genes, and intestinal toxicity is not imperative when DOT1L is rendered inactive in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23428873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Whereas mono-, di- and trimethylation states of lysines on histones typically have specific functions, no specific functions have been attributed so far to the different methylation states of histone H3 Lysine 79 (H3K79) generated by Dot1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18511943", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 998, "text": "Indeed, gene silencing in yeast, which is dependent on Dot1, relied on global H3K79 methylation levels and not on one specific methylation state. Furthermore, our findings suggest that histone H2B ubiquitination affects H3K79 trimethylation by enhancing synthesis of all H3K79 methylation states. Our results suggest that multiple methylation of H3K79 leads to a binary code, which is expected to limit the possibilities for regulation by putative demethylases or binding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18511943", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 479, "text": "ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human MLL-rearranged leukemias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18977325", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 360, "text": "To elucidate the mechanisms of genome reprogramming, we investigated histone H3 lysine 79 dimethylation (H3K79me2) and trimethylation (H3K79me3) in oocytes and preimplantation embryos via immunocytochemistry", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18003948", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 550, "text": "n somatic cells and oocytes, H3K79me2 was observed throughout the genome, whereas H3K79me3 was localized in the pericentromeric heterochromatin regions in which there are no active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18003948", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 942, "text": "Because H3K79me2 is considered an active gene marker, H3K79 methylation seems to have differing functions depending on the number of methyl groups added on the same residues. Both H3K79me2 and H3K79me3 decreased soon after fertilization, and the hypomethylated state was maintained at interphase (before the blastocyst stage), except for a transient increase in H3K79me2 at mitosis (M phase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18003948", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 999, "text": "ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285465", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1533, "text": "Conversion of H3K79 monomethylation into di- and trimethylation correlated with the transition from low- to high-level gene transcription. We also observed enrichment of H3K79 monomethylation at intergenic regions occupied by DNA-binding transcriptional activators. Our findings highlight several similarities between the patterning of H3K4 methylation and that of H3K79 methylation in mammalian chromatin, suggesting a widespread mechanism for parallel or sequential recruitment of DOT1L and MLL to genes in their normal \"on\" state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285465", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 611, "text": "URA3 reporter assays also indicated that H3K79 methylation is required for HM silencing. Surprisingly, a genome-wide expression analysis of H3K79 methylation-defective mutants identified only a few telomeric genes, such as COS12 at TEL-VII-L, to be subject to H3K79 methylation-dependent natural silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474073", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 860, "text": "Furthermore, H3K79 methylation by Dot1 did not play a role in the maintenance of natural HML silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21474073", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 553, "text": "Since the discovery \u223c10 years ago that Dot1 and its mammalian homolog, DOT1L (DOT1-Like), possess histone methyltransferase activity toward histone H3 Lys 79, great progress has been made in characterizing their enzymatic activities and the role of Dot1/DOT1L-mediated H3K79 methylation in transcriptional regulation, cell cycle regulation, and the DNA damage response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21724828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21741597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Inhibition of histone H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of breast cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25359765", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "H3K79 methylation directly precedes the histone-to-protamine transition in mammalian spermatids and is sensitive to bacterial infections", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "endSection": "title" }, { "offsetInBeginSection": 319, "offsetInEndSection": 434, "text": "in Drosophila spermatids, H3K79 methylation accompanies histone H4 hyperacetylation during chromatin reorganization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 971, "text": "In human and mice spermatids, di- and tri-methylated H3K79 temporally overlapped with hyperacetylated H4 and thus accompanied chromatin reorganization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "endSection": "abstract" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 1881, "text": "Our results indicated that H3K79 methylation is a histone modification conserved in Drosophila, mouse, rat and human spermatids and may be a prerequisite for proper chromatin reorganization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "During spermiogenesis, haploid spermatids undergo extensive chromatin remodeling events in which histones are successively replaced by more basic protamines to generate highly compacted chromatin. Here we show for the first time that H3K79 methylation is a conserved feature preceding the histone-to-protamine transition in Drosophila melanogaster and rat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 856, "text": "When acetylation was inhibited in cultured Drosophila testes, nuclei were smaller and chromatin was compact, Gpp was little synthesized, H3K79 methylation was strongly reduced, and protamines were not synthesized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190683", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Dot1-like protein (DOT1L) is an evolutionarily conserved histone methyltransferase that methylates lysine 79 of histone H3 (H3K79). Mammalian DOT1L participates in the regulation of transcription, development, erythropoiesis, differentiation, and proliferation of normal cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190683", "endSection": "abstract" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1409, "text": "H3K79 methylation is a critical histone modification that regulates cell proliferation and would be a novel histone mark for aging and cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190683", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1192, "text": "In rat, H3K79 methylation also correlates with H4 hyperacetylation but not with active RNA polymerase II, which might point towards a conserved function in chromatin remodeling during the histone-to-protamine transition in both Drosophila and rat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795146", "endSection": "abstract" } ] }, { "body": "Where can we find the protein lacritin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22918641", "http://www.ncbi.nlm.nih.gov/pubmed/23425695", "http://www.ncbi.nlm.nih.gov/pubmed/16982797", "http://www.ncbi.nlm.nih.gov/pubmed/22956620", "http://www.ncbi.nlm.nih.gov/pubmed/19770725", "http://www.ncbi.nlm.nih.gov/pubmed/19714880", "http://www.ncbi.nlm.nih.gov/pubmed/17850790", "http://www.ncbi.nlm.nih.gov/pubmed/11419941", "http://www.ncbi.nlm.nih.gov/pubmed/16865190", "http://www.ncbi.nlm.nih.gov/pubmed/22871838", "http://www.ncbi.nlm.nih.gov/pubmed/16488965", "http://www.ncbi.nlm.nih.gov/pubmed/14574570", "http://www.ncbi.nlm.nih.gov/pubmed/18334948", "http://www.ncbi.nlm.nih.gov/pubmed/23422824", "http://www.ncbi.nlm.nih.gov/pubmed/21087963", "http://www.ncbi.nlm.nih.gov/pubmed/16923831", "http://www.ncbi.nlm.nih.gov/pubmed/20375347", "http://www.ncbi.nlm.nih.gov/pubmed/15952718", "http://www.ncbi.nlm.nih.gov/pubmed/23482462", "http://www.ncbi.nlm.nih.gov/pubmed/22300579" ], "ideal_answer": [ "The protein lacritin can be found in lacrimal and salivary glands as well as in tear fluid and in the thyroid." ], "exact_answer": [ [ "lacrimal gland" ], [ "salivary glands" ], [ "thyroid" ], [ "tear fluid" ] ], "concepts": [ "http://www.uniprot.org/uniprot/LACRT_HUMAN" ], "type": "list", "id": "515b30d8d24251bc050000b0", "snippets": [ { "offsetInBeginSection": 197, "offsetInEndSection": 258, "text": "Lacritin, a glycoprotein secreted from lacrimal acinar cells,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23482462", "endSection": "sections.0" }, { "offsetInBeginSection": 139, "offsetInEndSection": 389, "text": "Essential for the viability of the surface epithelium of the eye and for normal vision is the thin, but protein-rich, tear film in which the small tear glycoprotein lacritin appears to play a prominent prosecretory, cytoprotective, and mitogenic role", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23425695", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 140, "text": "Lacritin is a prosecretory mitogen in tears and, although a tear protein, it promotes basal tearing and lacrimal gland secretion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422824", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11419941", "endSection": "title" }, { "offsetInBeginSection": 479, "offsetInEndSection": 717, "text": "Lacritin mRNA and protein are highly expressed in human lacrimal gland, moderately in major and minor salivary glands and slightly in thyroid. No lacritin message or protein is detected elsewhere among more than 50 human tissues examined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11419941", "endSection": "sections.0" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1198, "text": "and tear-specific proteins such as lacritin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16865190", "endSection": "sections.0" }, { "offsetInBeginSection": 234, "offsetInEndSection": 303, "text": "This study assessed lacritin levels in tears from healthy individuals", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918641", "endSection": "sections.0" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1109, "text": "The lipocalin 1, lactotransferrin, lacritin, lysozyme C, lipophilin A and immunoglobulin lambda chain were identified as possible biomarker candidates with significantly higher relative levels in the tear of patients with diabetic retinopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22300579", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 54, "text": "Lacritin is a novel human tear glycoprotein", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21087963", "endSection": "sections.0" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1569, "text": "In primates, lacritin was produced in the lacrimal gland and secreted into tear fluid.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17850790", "endSection": "sections.0" }, { "offsetInBeginSection": 708, "offsetInEndSection": 1069, "text": "Here we show by quantitative real-time PCR that lacritin is expressed in human breast tumors, breast cancer cell lines, and normal breast. The previously reported restricted expression pattern of lacritin is therefore incorrect. Lacritin transcripts were not detected in peripheral blood which makes lacritin a potential candidate as a breast cancer marker gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14574570", "endSection": "sections.0" } ] }, { "body": "Where can we find the protein dermcidin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23626547", "http://www.ncbi.nlm.nih.gov/pubmed/25055737", "http://www.ncbi.nlm.nih.gov/pubmed/25271322", "http://www.ncbi.nlm.nih.gov/pubmed/22448321", "http://www.ncbi.nlm.nih.gov/pubmed/24916439", "http://www.ncbi.nlm.nih.gov/pubmed/24969620", "http://www.ncbi.nlm.nih.gov/pubmed/24652391", "http://www.ncbi.nlm.nih.gov/pubmed/25347115", "http://www.ncbi.nlm.nih.gov/pubmed/22588119", "http://www.ncbi.nlm.nih.gov/pubmed/22262861", "http://www.ncbi.nlm.nih.gov/pubmed/24828484", "http://www.ncbi.nlm.nih.gov/pubmed/25330301", "http://www.ncbi.nlm.nih.gov/pubmed/24562771", "http://www.ncbi.nlm.nih.gov/pubmed/23426625", "http://www.ncbi.nlm.nih.gov/pubmed/24991806", "http://www.ncbi.nlm.nih.gov/pubmed/25485461", "http://www.ncbi.nlm.nih.gov/pubmed/22455996" ], "ideal_answer": [ "Dermcidin is a secretes protein found mainly in sweat but it is also found in serum.", "In previous work we reported the expression of Y-P30 \\/ dermcidin in maternal peripheral blood mononuclear cells and the transport of the protein to the fetal brain. In this study we analyzed hormonal regulation of Y-P30 in human immune cells and expression of Y-P30 in the placenta. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat demonstrated that sweat actively participates in the constitutive innate immune defense of human skin against infection. Several reports also state that peptides processed from the dermcidin precursor protein exhibit a range of other biological functions in neuronal and cancer cells. Using an immunoaffinity approach followed by multipoint validation, we identified the target of seriniquinone as the small protein, dermcidin. Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease. ``Pustulosis palmaris et plantaris'', or palmoplantar pustulosis, is a chronic pustular dermatitis characterized by intraepidermal palmoplantar pustules. Semi-quantitative dot-blot analysis revealed higher concentrations of hCAP-18 \\/ LL-37 in PPP-VF compared to healthy sweat. In conclusion, the expression of various AMPs is altered in acne vulgaris. " ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054805", "http://www.uniprot.org/uniprot/DCD_HUMAN" ], "type": "summary", "id": "54edd9c994afd61504000001", "snippets": [ { "offsetInBeginSection": 762, "offsetInEndSection": 940, "text": "In line with the extensive underrepresentation of proteins of the immune system, dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin secretome of ED patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25347115", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 671, "text": "Recently HSP70 has been shown to bind specifically to an N-terminal sequence of a human survival protein (DSEP, Dermcidin). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25485461", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 875, "text": " dermcidin (DCD) for sweat ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991806", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1197, "text": " Our data suggest that a source of Y-P30 apart from eccrine glands might be the placenta. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24969620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The mechanism of membrane permeabilization by dermcidin (DCD-1L), an antimicrobial peptide present in human sweat,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24652391", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 247, "text": " A stress-induced protein identified to be dermcidin isoform 2 of Mr. 11\u2009kDa from blood plasma of hypertensive persons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22448321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Dermcidin encodes the anionic amphiphilic peptide DCD-1L, which displays a broad spectrum of antimicrobial activity under conditions resembling those in human sweat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22262861", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 244, "text": "However, the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22455996", "endSection": "abstract" } ] }, { "body": "What is the triple screening test performed during pregnancy measuring?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7522195", "http://www.ncbi.nlm.nih.gov/pubmed/9333577", "http://www.ncbi.nlm.nih.gov/pubmed/11925409", "http://www.ncbi.nlm.nih.gov/pubmed/20120938", "http://www.ncbi.nlm.nih.gov/pubmed/18817910", "http://www.ncbi.nlm.nih.gov/pubmed/7688977", "http://www.ncbi.nlm.nih.gov/pubmed/18839465", "http://www.ncbi.nlm.nih.gov/pubmed/11920888" ], "ideal_answer": [ "Alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3)" ], "exact_answer": [ [ "AFP" ], [ "Estriol" ], [ "hCG" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011258" ], "type": "list", "id": "532f49f8d6d3ac6a34000035", "snippets": [ { "offsetInBeginSection": 1385, "offsetInEndSection": 1485, "text": "AFP--1.18 MoM and estriol--1.29 MoM and significantly higher mean median value for the free beta-hCG", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20120938", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1159, "text": "alpha-fetoprotein (AFP), 1.02 for human chorionic gonadotropin (hCG) and 1.01 for unconjugated estriol (uE3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18839465", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 238, "text": "alpha fetoprotein (AFP), beta human chorionic gonadotropin (beta-hCG), and unconjugated estriol (uE3) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18817910", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 579, "text": "alpha-fetoprotein (AFP), intact HCG and unconjugated estriol (uE3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11925409", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 559, "text": "lpha-fetoprotein (AFP), total beta human chorionic gonadotrophin (hCG) and estriol (uE(3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11920888", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 446, "text": "alpha feto-protein, HCG and unconjugated estriol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9333577", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 216, "text": "maternal serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated oestriol ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7522195", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 242, "text": "maternal serum alpha fetoprotein, unconjugated oestriol and human chorionic gonadotrophin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7688977", "endSection": "abstract" } ] }, { "body": "What are the generic versions of Viagra?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21054594", "http://www.ncbi.nlm.nih.gov/pubmed/22386826", "http://www.ncbi.nlm.nih.gov/pubmed/22925379", "http://www.ncbi.nlm.nih.gov/pubmed/21591526", "http://www.ncbi.nlm.nih.gov/pubmed/20338870", "http://www.ncbi.nlm.nih.gov/pubmed/14662775", "http://www.ncbi.nlm.nih.gov/pubmed/21324833" ], "ideal_answer": [ "Generic versions of sildenafil are Elonza, Caverta, Zenegra-100, Vega Asia, Suhagra-100, Vega, Revatio." ], "exact_answer": [ [ "Elonza" ], [ "Caverta" ], [ "Zenegra-100" ], [ "Vega Asia" ], [ "Suhagra-100" ], [ "Vega" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016568", "http://www.biosemantics.org/jochem#4266960" ], "type": "list", "id": "5150f401d24251bc05000075", "snippets": [ { "offsetInBeginSection": 363, "offsetInEndSection": 487, "text": "The authors conducted a 12-week case series to study the efficacy and safety of Elonza (generic sildenafil) in PAH patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21591526", "endSection": "sections.0" } ] }, { "body": "Which protein interacts with the Ragulator-RAG GTPases to control mTOR activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25561175", "http://www.ncbi.nlm.nih.gov/pubmed/25567906", "http://www.ncbi.nlm.nih.gov/pubmed/25963655" ], "ideal_answer": [ "Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery that controls the activation of mTOR.", "SLC38A9 localizes with Rag-Ragulator complex components on lysosomes and associates with Rag GTPases in an amino acid-sensitive and nucleotide binding state-dependent manner. Depletion of SLC38A9 inhibits mTORC1 activity in the presence of amino acids and in response to amino acid replenishment following starvation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR. The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to many cues, such as nutrient status and energy level." ], "exact_answer": [ "Amino Acid-DepeLysosomal Membrane Protein SLC38A9" ], "type": "factoid", "id": "56caea805795f9a73e00002c", "snippets": [ { "offsetInBeginSection": 1042, "offsetInEndSection": 1182, "text": "Together, the findings of our study reveal SLC38A9 as a Rag-Ragulator complex member transducing amino acid availability to mTORC1 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963655", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 1070, "text": "Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery. Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal, whereas loss of SLC38A9 expression impaired amino-acid-induced mTORC1 activation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561175", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 409, "text": "Here, we identify the human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag-Ragulator complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963655", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 584, "text": "SLC38A9 localizes with Rag-Ragulator complex components on lysosomes and associates with Rag GTPases in an amino acid-sensitive and nucleotide binding state-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963655", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1181, "text": "Together, the findings of our study reveal SLC38A9 as a Rag-Ragulator complex member transducing amino acid availability to mTORC1 activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963655", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 787, "text": "Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561175", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 604, "text": "Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567906", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 604, "text": "Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567906", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 411, "text": "Amino acids induce mTORC1 activation on lysosomes via the small Rag GTPases and the Ragulator complex, thereby controlling protein translation and cell growth. Here, we identify the human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag-Ragulator complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963655", "endSection": "abstract" } ] }, { "body": "Against which organisms has reverse vaccinology been used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23527566", "http://www.ncbi.nlm.nih.gov/pubmed/22261504", "http://www.ncbi.nlm.nih.gov/pubmed/16107075", "http://www.ncbi.nlm.nih.gov/pubmed/23514126", "http://www.ncbi.nlm.nih.gov/pubmed/17291333", "http://www.ncbi.nlm.nih.gov/pubmed/16848907", "http://www.ncbi.nlm.nih.gov/pubmed/22521592", "http://www.ncbi.nlm.nih.gov/pubmed/20127115", "http://www.ncbi.nlm.nih.gov/pubmed/21993656", "http://www.ncbi.nlm.nih.gov/pubmed/20671958", "http://www.ncbi.nlm.nih.gov/pubmed/22434357", "http://www.ncbi.nlm.nih.gov/pubmed/23533646", "http://www.ncbi.nlm.nih.gov/pubmed/12531326", "http://www.ncbi.nlm.nih.gov/pubmed/11257410", "http://www.ncbi.nlm.nih.gov/pubmed/19179021" ], "ideal_answer": [ "Reverse Vaccinology (RV) was first applied to serogroup B Neisseria meningitidis. This work induced further research of other pathogens in the same way: Porphyromonas gingivalis, Streptococcus pneumoniae, Chlamydia pneumoniae, Bacillus anthracis, group B streptococci, Helicobacter pylori and Mycobacterium tuberculosis. Concerning animal-affecting organisms, RV has been applied for vaccine design against Theileria parva, Brachyspira hyodysenteriae, Echinococcus granulosus, Ehrlichia ruminantium, Leishmania spp, Rhipicephalus microplus and Brucella melitensis." ], "exact_answer": [ [ "Neisseria meningitidis (serogroup B)" ], [ "Porphyromonas gingivalis" ], [ "Streptococcus pneumoniae" ], [ "Chlamydia pneumoniae" ], [ "Bacillus anthracis" ], [ "group B streptococci" ], [ "Helicobacter pylori" ], [ "Mycobacterium tuberculosis" ], [ "Theileria parva" ], [ "Brachyspira hyodysenteriae" ], [ "Echinococcus granulosus" ], [ "Ehrlichia ruminantium" ], [ "Leishmania spp" ], [ "Rhipicephalus microplus" ], [ "Brucella melitensis" ] ], "type": "list", "id": "51601071298dcd4e51000038", "snippets": [ { "offsetInBeginSection": 762, "offsetInEndSection": 912, "text": "The potential of this new approach is illustrated by the use of reverse vaccinology for the development of a vaccine against serogroup B meningococcus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11257410", "endSection": "sections.0" }, { "offsetInBeginSection": 858, "offsetInEndSection": 946, "text": "The Neisseria meningitidis serogroup B project, the first example of Reverse Vaccinology", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12531326", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Reverse vaccinology and vaccines for serogroup B Neisseria meningitidis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16107075", "endSection": "title" }, { "offsetInBeginSection": 434, "offsetInEndSection": 539, "text": "This process, first applied to serogroup B Neisseria meningitidis, has been termed as reverse vaccinology", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16107075", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "A reverse vaccinology approach to swine dysentery vaccine development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19179021", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Swine dysentery (SD) is a mucohaemorrhagic colitis of pigs resulting from infection of the large intestine with the anaerobic intestinal spirochaete Brachyspira hyodysenteriae", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19179021", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Reverse vaccinology approach identify an Echinococcus granulosus tegumental membrane protein enolase as vaccine candidate", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20127115", "endSection": "title" }, { "offsetInBeginSection": 2039, "offsetInEndSection": 2148, "text": "Reverse vaccinology process identified E. granulosus tegumental membrane protein enolase as vaccine candidate", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20127115", "endSection": "sections.0" }, { "offsetInBeginSection": 868, "offsetInEndSection": 979, "text": "The application of RV to Neisseria meningitidis serogroup B represents the first success of this novel approach", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993656", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Identification of Ehrlichia ruminantium proteins that activate cellular immune responses using a reverse vaccinology strategy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261504", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Ehrlichia ruminantium is an obligate intracellular bacterial pathogen which causes heartwater, a serious tick-borne disease of ruminants throughout sub-Saharan Africa", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261504", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "A reverse vaccinology approach for the identification of potential vaccine candidates from Leishmania spp", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22434357", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "A systematic, functional genomics, and reverse vaccinology approach to the identification of vaccine candidates in the cattle tick, Rhipicephalus microplus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22521592", "endSection": "title" } ] }, { "body": "Galassi classification is used for which disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16096939", "http://www.ncbi.nlm.nih.gov/pubmed/14676729", "http://www.ncbi.nlm.nih.gov/pubmed/10663819", "http://www.ncbi.nlm.nih.gov/pubmed/12922037", "http://www.ncbi.nlm.nih.gov/pubmed/18704305", "http://www.ncbi.nlm.nih.gov/pubmed/23696293", "http://www.ncbi.nlm.nih.gov/pubmed/12218836" ], "ideal_answer": [ "Galassi classification system is used to classify arachnoid cysts." ], "exact_answer": [ "arachnoid cyst" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002965" ], "type": "factoid", "id": "56c1f021ef6e394741000048", "snippets": [ { "offsetInBeginSection": 282, "offsetInEndSection": 373, "text": " All these patients were divided into three subgroups according to Galassi classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18704305", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 820, "text": "We are led to conclude that Fenestration is suitable for cysts of types I and II (Galassi classification), cysto-peritoneal shunting is better for cysts of type III.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18704305", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 580, "text": "According to Galassi classification they were subdivided into 3 groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14676729", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 575, "text": "According to Galassi classification they were subdivided in three groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12922037", "endSection": "abstract" }, { "offsetInBeginSection": 2052, "offsetInEndSection": 2188, "text": "On follow-up CT scan and MRI, cysts of types I and II (Galassi classification) exhibited a steady tendency to reduction or obliteration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10663819", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 813, "text": "All cysts were type II according to Galassi classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16096939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Chronic subdural hemorrhage into a giant arachnoidal cyst (Galassi classification type III).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218836", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The authors present CT and MRI of a patient with an extremely large arachnoidal cyst (Galassi classification type III). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The authors present CT and MRI of a patient with an extremely large arachnoidal cyst (Galassi classification type III).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Unusual volume reduction of Galassi grade III arachnoid cyst following head trauma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23696293", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The authors present CT and MRI of a patient with an extremely large arachnoidal cyst (Galassi classification type III).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218836", "endSection": "abstract" } ] }, { "body": "Describe Mozart effect.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25383198", "http://www.ncbi.nlm.nih.gov/pubmed/21689988", "http://www.ncbi.nlm.nih.gov/pubmed/23154636", "http://www.ncbi.nlm.nih.gov/pubmed/12509211", "http://www.ncbi.nlm.nih.gov/pubmed/23304207", "http://www.ncbi.nlm.nih.gov/pubmed/11437309", "http://www.ncbi.nlm.nih.gov/pubmed/23724071", "http://www.ncbi.nlm.nih.gov/pubmed/21292560", "http://www.ncbi.nlm.nih.gov/pubmed/10407891", "http://www.ncbi.nlm.nih.gov/pubmed/25060169", "http://www.ncbi.nlm.nih.gov/pubmed/23540417" ], "ideal_answer": [ "The Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448." ], "type": "summary", "id": "56c1f027ef6e394741000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart Effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25383198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "According to the first publication in 1993 by Rauscher et al. [Nature 1993;365:611], the Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25060169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The Mozart Effect is a phenomenon whereby certain pieces of music induce temporary enhancement in \"spatial temporal reasoning.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23540417", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 712, "text": "Here, we investigated the cerebellar role in the association between spatial and musical domains, by testing performances in embodied (EMR) or abstract (AMR) mental rotation tasks of subjects listening Mozart Sonata K.448, which is reported to improve spatial-temporal reasoning, in the presence or in the absence of continuous theta burst stimulation (cTBS) of the left cerebellar hemisphere. In the absence of cerebellar cTBS, music listening did not influence either MR task, thus not revealing a \"Mozart Effect\". ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23304207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Mozart's Sonata for two pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21292560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Mozart's Sonata for Two Pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart Effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21689988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Mozart's Sonata for Two Pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart Effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21689988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23540417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The \"Mozart effect\" refers to claims that people perform better on tests of spatial abilities after listening to music composed by Mozart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11437309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart Effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25383198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The Mozart effect is an increase in spatial reasoning scores detected immediately after listening to the first movement of a Mozart piano sonata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10407891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The \"Mozart effect\" is the tendency to score higher on spatiotemporal IQ subscales following exposure to complex music such as Mozart's Sonata K.448.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12509211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23304207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": " Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart Effect. However, most of these reports only describe the phenomena but lack the scientific evidence needed to properly investigate the mechanism of Mozart Effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25383198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": " The Mozart effect is an increase in spatial reasoning scores detected immediately after listening to the first movement of a Mozart piano sonata. Rauscher and Shaw (1998) suggested that failure to produce a Mozart effect could arise from carryover effects of a spatial reasoning pretest which may interfere with the effect of listening to Mozart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10407891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23304207", "endSection": "abstract" } ] }, { "body": "What is the purpose of the Tokuhashi scoring system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24212518", "http://www.ncbi.nlm.nih.gov/pubmed/17593839", "http://www.ncbi.nlm.nih.gov/pubmed/23328875", "http://www.ncbi.nlm.nih.gov/pubmed/21223698", "http://www.ncbi.nlm.nih.gov/pubmed/21772622", "http://www.ncbi.nlm.nih.gov/pubmed/21796024", "http://www.ncbi.nlm.nih.gov/pubmed/22973387", "http://www.ncbi.nlm.nih.gov/pubmed/25085251", "http://www.ncbi.nlm.nih.gov/pubmed/25035829", "http://www.ncbi.nlm.nih.gov/pubmed/17094910" ], "ideal_answer": [ "Tokuhashi scoring system was developed to predict life expectancy of patients with spinal metastases. The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease." ], "type": "summary", "id": "56bcd422d36b5da378000005", "snippets": [ { "offsetInBeginSection": 409, "offsetInEndSection": 746, "text": " Those referring to representative scoring systems about predicting the survival of patients with metastatic spine tumors were used. The significance and limits of these scoring systems, and the future perspectives were described. Tokuhashi score, Tomita score, Baur score, Linden score, Rades score, and Katagiri score were introduced. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25035829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "BACKGROUND: We sought to identify preoperative factors significantly correlated with survival. We also aimed to evaluate the validity of the prognostic scores in the Tomita and Tokuhashi systems and discuss several aspects to improve the predictive accuracy of these systems. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25085251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Accuracy of the revised Tokuhashi score in predicting survival in patients with metastatic spinal cord compression (MSCC).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328875", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "PURPOSE: The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328875", "endSection": "abstract" }, { "offsetInBeginSection": 2501, "offsetInEndSection": 2910, "text": "CONCLUSION: We would conclude that although the predictive value of the Tokuhashi score in terms of survival time is at best modest (66 %), the fact that there were statistically significant differences in survival between the groups looked at in this paper indicates that the scoring system, and the components which it consists of, are important in the evaluation of these patients when considering surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Tokuhashi Scoring System has limited applicability in the majority of patients with spinal cord compression secondary to vertebral metastasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212518", "endSection": "title" }, { "offsetInBeginSection": 166, "offsetInEndSection": 235, "text": "The Tokuhashi Scoring System (TSS) is a widely used prognostic tool. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Predictive value of Tokuhashi scoring systems in spinal metastases, focusing on various primary tumor groups: evaluation of 448 patients in the Aarhus spinal metastases database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21796024", "endSection": "title" }, { "offsetInBeginSection": 125, "offsetInEndSection": 294, "text": "OBJECTIVE: To determine the specific predictive value of the Tokuhashi scoring system (T12) and its revised version (T15) in spinal metastases of various primary tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21796024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Is Tokuhashi score suitable for evaluation of life expectancy before surgery in Iranian patients with spinal metastases?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973387", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "BACKGROUND: One of the most important selection criteria for spinal metastases surgery is life expectancy and the most important system for this prediction has been proposed by Tokuhashi. The aim of this study was to evaluate predictive value of the Tokuhashi score for life expectancy in Iranian patients with spinal metastases one year after diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973387", "endSection": "abstract" }, { "offsetInBeginSection": 1319, "offsetInEndSection": 1508, "text": "CONCLUSIONS: Present study showed that the Tokuhashi revised scoring system may be practicable and highly predictive preoperative scoring system for patients with spinal metastases in Iran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973387", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 546, "text": "This study was to evaluate Tomita and Tokuhashi scoring systems in selecting surgical procedure and predicting prognosis of extradural spinal metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17094910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Analysis of the predictive role and new proposal for surgical strategies based on the modified Tomita and Tokuhashi scoring systems for spinal metastasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25085251", "endSection": "title" }, { "offsetInBeginSection": 183, "offsetInEndSection": 306, "text": "We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21772622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "[The predictive value of the Tokuhashi revised scoring system for the survival time of patients with spinal metastases].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17593839", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "To evaluate the predictive value of the Tokuhashi revised scoring system for the life expectancy of patients with spinal metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17593839", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 427, "text": "To determine the specific predictive value of the Tokuhashi scoring system (T12) and its revised version (T15) in spinal metastases of various primary tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21796024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "To evaluate the predictive values of Tokuhashi score, revised Tokuhashi score and Tomita score systems for life expectancy and treatment options in patients with spinal metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21223698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Tokuhashi Scoring System has limited applicability in the majority of patients with spinal cord compression secondary to vertebral metastasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212518", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "[The predictive value of the Tokuhashi revised scoring system for the survival time of patients with spinal metastases]", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17593839", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "To evaluate the predictive value of the Tokuhashi revised scoring system for the life expectancy of patients with spinal metastases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17593839", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 183, "text": "We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21772622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "PURPOSE: The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328875", "endSection": "abstract" } ] }, { "body": "Which compounds exist that are thyroid hormone analogs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "http://www.ncbi.nlm.nih.gov/pubmed/12010632", "http://www.ncbi.nlm.nih.gov/pubmed/6327972", "http://www.ncbi.nlm.nih.gov/pubmed/19074582", "http://www.ncbi.nlm.nih.gov/pubmed/17164749", "http://www.ncbi.nlm.nih.gov/pubmed/3359982", "http://www.ncbi.nlm.nih.gov/pubmed/16384862", "http://www.ncbi.nlm.nih.gov/pubmed/19903697", "http://www.ncbi.nlm.nih.gov/pubmed/21239431", "http://www.ncbi.nlm.nih.gov/pubmed/15148346", "http://www.ncbi.nlm.nih.gov/pubmed/10329215", "http://www.ncbi.nlm.nih.gov/pubmed/20937391", "http://www.ncbi.nlm.nih.gov/pubmed/3756504", "http://www.ncbi.nlm.nih.gov/pubmed/3707599", "http://www.ncbi.nlm.nih.gov/pubmed/8301561", "http://www.ncbi.nlm.nih.gov/pubmed/15572044", "http://www.ncbi.nlm.nih.gov/pubmed/21670063" ], "ideal_answer": [ "Compoounds such as 3,5-diiodo-L-thyronine, T2, GC-24, CO23, DITPA, 3,5-diiodothyropropionic acid, GC-1, Tetrac, 3,3',5,5'-tetraiodo-thyroacetic acid, KB- 2115, KB - 141, thyronamines, T4-agarose, CGS 23425, D-T3, 3,3',5-triiodo-D-thyronine, 3,5-T2, 3,5-diiodo-L-thyronine, DIT, 3,5-diiodo-L-tyrosine, MIT, 3-monoiodo-L-tyrosine, triac, 3, 3',5-triiodo-thyroacetic acid, 3,5-Diiodo-4-hydroxyphenylpropionic acid, DIHPA, 3,5-Dimethyl-3'-isopropyl-L-thyronine, DIMIT, 3,5-diiodo-3'-isopropylthyroacetic acid and IpTA2 are compounds that are thyroid hormone analogs." ], "exact_answer": [ [ "3,5-diiodo-L-thyronine", "T2" ], [ "GC-24" ], [ "CO23" ], [ "DITPA", "3,5-diiodothyropropionic acid" ], [ "GC-1" ], [ "Tetrac", "3,3',5,5'-tetraiodo-thyroacetic acid" ], [ "KB-2115" ], [ "KB-141" ], [ "thyronamines" ], [ "T4-agarose" ], [ "CGS 23425" ], [ "D-T3", "3,3',5-triiodo-D-thyronine" ], [ "3,5-T2", "3,5-diiodo-L-thyronine" ], [ "DIT", "3,5-diiodo-L-tyrosine" ], [ "MIT", "3-monoiodo-L-tyrosine" ], [ "triac", "3,3',5-triiodo-thyroacetic acid" ], [ "3,5-Diiodo-4-hydroxyphenylpropionic acid", "DIHPA" ], [ "3,5-Dimethyl-3'-isopropyl-L-thyronine", "DIMIT" ], [ "3,5-diiodo-3'-isopropylthyroacetic acid", "IpTA2" ] ], "type": "list", "id": "515993f3d24251bc050000a0", "snippets": [ { "offsetInBeginSection": 397, "offsetInEndSection": 459, "text": "naturally occurring iodothyronine, 3,5-diiodo-L-thyronine (T2)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21670063", "endSection": "sections.0" }, { "offsetInBeginSection": 24, "offsetInEndSection": 94, "text": "thyroid hormone receptor beta- and \u03b1-selective agonists GC-24 and CO23", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21239431", "endSection": "title" }, { "offsetInBeginSection": 511, "offsetInEndSection": 591, "text": "two thyroid hormone agonists, the TR\u03b2-selective GC-24 and the TR\u03b1-selective CO23", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21239431", "endSection": "sections.0" }, { "offsetInBeginSection": 221, "offsetInEndSection": 303, "text": "Diiodothyropropionic acid (DITPA) and GC-1, a noniodinated thyroid hormone analog,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19903697", "endSection": "sections.0" }, { "offsetInBeginSection": 400, "offsetInEndSection": 422, "text": "analogs DITPA and GC-1", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19903697", "endSection": "sections.0" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1310, "text": "Tetrac inhibits binding of thyroid hormone analogs to the receptor on alphavbeta3 and lacks thyromimetic activity at this site", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19903697", "endSection": "sections.0" }, { "offsetInBeginSection": 309, "offsetInEndSection": 344, "text": "thyroid hormone agonist, called GC1", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "endSection": "sections.0" }, { "offsetInBeginSection": 525, "offsetInEndSection": 576, "text": "Other selective thyromimetic, KB- 2115 and KB - 141", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "endSection": "sections.0" }, { "offsetInBeginSection": 599, "offsetInEndSection": 657, "text": "Another class of thyroid hormone analogs, the thyronamines", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18954857", "endSection": "sections.0" }, { "offsetInBeginSection": 355, "offsetInEndSection": 399, "text": "T4-agarose, a formulation of thyroid hormone", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17164749", "endSection": "sections.0" }, { "offsetInBeginSection": 27, "offsetInEndSection": 90, "text": "he thyroid hormone analog 3,5-diiodothyropropionic acid (DITPA)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16384862", "endSection": "title" }, { "offsetInBeginSection": 855, "offsetInEndSection": 913, "text": "The thyroid hormone analogs DITPA, T(4), and T(4)-agarose,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16384862", "endSection": "sections.0" }, { "offsetInBeginSection": 330, "offsetInEndSection": 392, "text": ",5-diiodothyropropionic acid (DITPA), a thyroid hormone analog", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16384862", "endSection": "sections.0" }, { "offsetInBeginSection": 71, "offsetInEndSection": 138, "text": "thyroid hormone analogs 3,5-diiodothyropropionic acid and CGS 23425", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15148346", "endSection": "title" }, { "offsetInBeginSection": 328, "offsetInEndSection": 408, "text": "wo thyroid hormone analogs, 3,5-diidodothyropropionic acid (DITPA) and CGS 23425", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15148346", "endSection": "sections.0" }, { "offsetInBeginSection": 156, "offsetInEndSection": 482, "text": "several thyroid hormone analogs, including T4(3,3',5,5'-tetraiodo-L-thyronine), rT3(3,3',5'-triiodo-L-thyronine), D-T3(3,3',5-triiodo-D-thyronine), 3,5-T2(3,5-diiodo-L-thyronine), DIT (3,5-diiodo-L-tyrosine), MIT (3-monoiodo-L-tyrosine), tetrac (3,3',5,5'-tetraiodo-thyroacetic acid), triac (3, 3',5-triiodo-thyroacetic acid),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10329215", "endSection": "sections.0" }, { "offsetInBeginSection": 440, "offsetInEndSection": 588, "text": ",5-Diiodo-4-hydroxyphenylpropionic acid (DIHPA) was found to bind specifically to bacterially expressed alpha-1 and beta-1 thyroid hormone receptors", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8301561", "endSection": "sections.0" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1503, "text": "DIHPA is a novel thyromimetic compound", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8301561", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Identification of simple substituted phenols with thyromimetic activity: cardiac effects of 3,5-diiodo-4-hydroxyphenylpropionic acid", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8301561", "endSection": "title" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1276, "text": "The relative affinity of the receptor for thyroid hormone analogs was triiodothyroacetic acid = T3 greater than T4 greater than tetraiodothyroacetic acid in oligodendrocyte and astrocyte nuclei", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3359982", "endSection": "sections.0" }, { "offsetInBeginSection": 786, "offsetInEndSection": 955, "text": "The relative binding affinity of the receptor for thyroid hormone analogs was in the order TRIAC greater than L-T3 greater than D-T3 greater than L-T4 in both cell lines", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3756504", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'-isopropylthyroacetic acid (IpTA2), two thyroid hormone analogs,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3707599", "endSection": "sections.0" }, { "offsetInBeginSection": 82, "offsetInEndSection": 252, "text": "synthetic thyroid analogs (3,5,3'-L-triiodothyronine, 3,5,3'-D-triiodothyronine, 3,3',5'-L- triiodothyronine , 3,5,3'-L-triiodothyroacetic acid and 3,5-L-diiodothyronine)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6327972", "endSection": "sections.0" }, { "offsetInBeginSection": 267, "offsetInEndSection": 508, "text": "In the present study, we characterized the interactions of the synthetic triiodo L-thyronine analogs and thyroid hormone nuclear receptor TR\u03b2-selective agonists GC-1 and GC-24 with the wild type and V30M variant of human transthyretin (TTR).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937391", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "3-Iodothyronamine (T(1)AM) is a naturally occurring thyroid hormone metabolite with distinct biological effects that are opposite those of thyroid hormone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074582", "endSection": "sections.0" } ] }, { "body": "Is lenvatinib effective for thyroid cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25974026", "http://www.ncbi.nlm.nih.gov/pubmed/26105190", "http://www.ncbi.nlm.nih.gov/pubmed/26316818", "http://www.ncbi.nlm.nih.gov/pubmed/25553081", "http://www.ncbi.nlm.nih.gov/pubmed/25671254", "http://www.ncbi.nlm.nih.gov/pubmed/25913680" ], "ideal_answer": [ "Yes, lenvatinib is effective for thyroid cancer." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3963", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013964", "http://www.disease-ontology.org/api/metadata/DOID:1781" ], "type": "yesno", "id": "56c1f002ef6e394741000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "New insights in the treatment of radioiodine refractory differentiated thyroid carcinomas: to lenvatinib and beyond.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25974026", "endSection": "title" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1377, "text": "However, even more impressive responses and progression-free survival benefits were seen in the phase III SELECT trial with lenvatinib, giving even higher hopes for the future management of what was considered just a decade ago an orphan disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25974026", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 741, "text": "Sorafenib and lenvatinib, small-molecule multikinase inhibitors, were approved for the treatment of progressive, symptomatic, radioactive iodine refractory, advanced differentiated thyroid cancer in 2013 and 2015, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26105190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25913680", "endSection": "title" }, { "offsetInBeginSection": 1811, "offsetInEndSection": 2021, "text": "CONCLUSIONS: In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25913680", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 488, "text": "Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer - cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26316818", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 970, "text": "Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25553081", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 486, "text": "Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer - cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26316818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 654, "text": "BACKGROUND: Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor \ufffd, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).METHODS: In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25671254", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 803, "text": "Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodine-refractory, differentiated thyroid cancer (RR-DTC).METHODS: Fifty-eight patients with RR-DTC who had disease progression during the previous 12 months received lenvatinib 24 mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25913680", "endSection": "abstract" } ] }, { "body": "What genes are related to breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24327800", "http://www.ncbi.nlm.nih.gov/pubmed/21123097", "http://www.ncbi.nlm.nih.gov/pubmed/22695536", "http://www.ncbi.nlm.nih.gov/pubmed/23678008", "http://www.ncbi.nlm.nih.gov/pubmed/23358415", "http://www.ncbi.nlm.nih.gov/pubmed/24272208", "http://www.ncbi.nlm.nih.gov/pubmed/24289229", "http://www.ncbi.nlm.nih.gov/pubmed/24183724", "http://www.ncbi.nlm.nih.gov/pubmed/24302665", "http://www.ncbi.nlm.nih.gov/pubmed/23318652", "http://www.ncbi.nlm.nih.gov/pubmed/24319537", "http://www.ncbi.nlm.nih.gov/pubmed/18485221", "http://www.ncbi.nlm.nih.gov/pubmed/24298072", "http://www.ncbi.nlm.nih.gov/pubmed/17132159", "http://www.ncbi.nlm.nih.gov/pubmed/24026986", "http://www.ncbi.nlm.nih.gov/pubmed/24324792", "http://www.ncbi.nlm.nih.gov/pubmed/24296317" ], "ideal_answer": [ "Breast cancer is a disease in which certain cells in the breast become abnormal and multiply without control or order to form a tumor. The most common form of breast cancer begins in cells lining the ducts that carry milk to the nipple (ductal cancer). Other forms of breast cancer begin in the glands that produce milk (lobular cancer) or in other parts of the breast.\nEarly breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, or scaliness. These changes can occur as part of many different conditions, however. Having one or more of these symptoms does not mean that a person definitely has breast cancer.\nIn some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.\nA small percentage of all breast cancers cluster in families. Hereditary cancers are those associated with inherited gene mutations. Hereditary breast cancers tend to occur earlier in life than noninherited (sporadic) cases and are more likely to involve both breasts.\n\nVariations of the BRCA1, BRCA2, BRCT, and P53 genes increase the risk of developing breast cancer.\nThe and NFR2, HER2 and TOP2A genes are associated with breast cancer." ], "exact_answer": [ [ "p53", "TP53" ], [ "BRCA2" ], [ "NRF2" ], [ "BRCA1" ], [ "BRCT" ], [ "HER2", "ERBB2", "RPS2" ], [ "TOP2A" ], [ "TRIM22" ] ], "concepts": [ "http://www.uniprot.org/uniprot/BIN2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.disease-ontology.org/api/metadata/DOID:1612", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943", "http://www.disease-ontology.org/api/metadata/DOID:0050671", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052138" ], "type": "list", "id": "53357c98d6d3ac6a3400004a", "snippets": [ { "offsetInBeginSection": 1055, "offsetInEndSection": 1279, "text": "Network analysis showed increased expression of a majority of components in p53 and BRCA1 subnetworks in AA breast tumor samples, and members of the aurora B and polo-like kinase signaling pathways were also highly expressed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324792", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1453, "text": "These results indicate that nuclear NRF2 protein plays important roles in the proliferation and/or progression of breast carcinoma, and nuclear NRF2 immunoreactivity is therefore considered a potent prognostic factor in breast cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24302665", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 535, "text": "Our previous studies in breast cancer cells indicate that 2CdA and F-ara-A are involved in epigenetic regulation of gene transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24296317", "endSection": "abstract" }, { "offsetInBeginSection": 1642, "offsetInEndSection": 1833, "text": " It seems to be a new important element of ClF anticancer activity and may indicate its potential efficacy in epigenetic therapy of solid tumours, especially at early stages of carcinogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24296317", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 558, "text": "many molecular components that regulate HR are tumour suppressors p53, a negative regulator and breast cancer early-onset (BRCA)2, a positive regulator. Both the players not only interact with each other but also directly interact with human RAD51 (hRAD51), the key recombinase in HR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23678008", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1270, "text": " Our findings suggest a rigorous p53-mediated regulation on hRAD51 functions in HR even in the presence of BRCA2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23678008", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 460, "text": "coordinated replication and transcription of pericentromeric repeats enable RNA interference (RNAi)-mediated transmission of pericentromeric heterochromatin in fission yeast, which is essential for the proper function of centromeres. Rad3/ATR kinase phosphorylates histone H2A on serine-128/-129 to create \u03b3H2A in pericentromeric heterochromatin during S phase, which recruits Brc1 through its breast cancer gene 1 protein (BRCA1) C-terminal (BRCT) domains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23358415", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 186, "text": "protein BRCA2 affect its interactions with the recombinase RAD51 and are associated with an increased risk of cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21123097", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 765, "text": " serial deletion mutation experiments, binding strengths were increased when the C-terminal BRC repeat was removed from BRC1-8, BRC1-5 and BRC1-3. These results may provide an insight into the effects of missense or truncation mutations in BRCA2 in canine tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21123097", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 504, "text": "Triple-negative breast cancers (TNBC) do not represent a single disease subgroup and are often aggressive breast cancers with poor prognoses. Unlike estrogen/progesterone receptor and HER2 (human epidermal growth factor receptor 2) breast cancers, which are responsive to targeted treatments, there is no effective targeted therapy for TNBC, although approximately 50% of patients respond to conventional chemotherapies, including taxanes, anthracyclines, cyclophosphamide, and platinum salts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298072", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 197, "text": "Genetic BRCA2 insufficiency is associated with breast cancer development; however, in sporadic breast cancer cases, high BRCA2 expression is paradoxically correlated with poor prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289229", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1749, "text": "HER-2 and TOP2A gene amplification showed a tendency to be associated with larger tumor size, positive lymph node status, high level of apoptotic and proliferative indexes, and low level of p53 and Bcl-2 expression, which all together indicate group of patients with similar outcome during the progression of the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24272208", "endSection": "abstract" } ] }, { "body": "To the ligand of which receptors does Denosumab (Prolia) bind?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23616122", "http://www.ncbi.nlm.nih.gov/pubmed/23241893", "http://www.ncbi.nlm.nih.gov/pubmed/19098925", "http://www.ncbi.nlm.nih.gov/pubmed/22338309", "http://www.ncbi.nlm.nih.gov/pubmed/22322981", "http://www.ncbi.nlm.nih.gov/pubmed/22815185", "http://www.ncbi.nlm.nih.gov/pubmed/21243489", "http://www.ncbi.nlm.nih.gov/pubmed/16527005", "http://www.ncbi.nlm.nih.gov/pubmed/18632461", "http://www.ncbi.nlm.nih.gov/pubmed/16188502", "http://www.ncbi.nlm.nih.gov/pubmed/22401778", 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"http://linkedlifedata.com/resource/umls/label/A17699205", "o": "NCI Thesaurus" } ], "ideal_answer": [ "Denosumab is a monoclonal antibody against the RANKL" ], "exact_answer": [ "RANKL" ], "concepts": [ "http://www.biosemantics.org/jochem#4268082", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030547", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900120", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900121", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0038023" ], "type": "factoid", "id": "52bf1d9e03868f1b06000010", "snippets": [ { "offsetInBeginSection": 414, "offsetInEndSection": 619, "text": "Whether the factor has the same role in humans is of clinical interest because an inhibitor for RANKL, denosumab, is already used for the treatment of bone disease and might benefit breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23616122", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1028, "text": "Treatment of AML cells with the clinically available RANKL Ab Denosumab resulted in enhanced NK cell anti-leukemia reactivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23241893", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1653, "text": "The emerging clinical implication, supported by recent epidemiological studies, is that \u03b2AR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the \"vicious cycle\" of bone destruction induced by these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815651", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 822, "text": "Both the effects of RANKL on osteoclastogenesis and cytokine production by malignant cells could be blocked by disruption of RANK-RANKL interaction with denosumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23139212", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 1598, "text": "In the future, the armamentarium against osteoporotic fractures will likely be enriched by (1.) new bone anabolic substances such as antibodies directed against the endogenous inhibitors of bone formation sclerostin and dickkopf-1, PTH and PTHrp analogues, and possibly calcilytics; (2.) new inhibitors of bone resorption such as cathepsin K inhibitors which may suppress osteoclast function without impairing osteoclast viability and thus maintain bone formation by preserving the osteoclast-osteoblast crosstalk, and denosumab, an already widely available antibody against RANKL which inhibits osteoclast formation, function, and survival; and (3.) new therapeutic strategies based on an extended understanding of the pathophysiology of osteoporosis which may include sequential therapies with two or more bone active substances aimed at optimising the management of bone capital acquired during adolescence and maintained during adulthood in terms of both quantity and quality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815185", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 606, "text": "Clearly, the approval of denosumab, a monoclonal antibody directed against RANKL, has just marked the beginning of a new era for bone therapy with several additional new therapies lining up for clinical approval in the coming years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22401778", "endSection": "abstract" }, { "offsetInBeginSection": 1922, "offsetInEndSection": 2054, "text": "Denosumab is a fully human monoclonal antibody to RANK Ligand that is administered as a 60-mg subcutaneous injection every 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22338309", "endSection": "abstract" }, { "offsetInBeginSection": 1478, "offsetInEndSection": 1617, "text": "More recently, a nuclear factor-\u03b2 ligand (RANKL) inhibitor, denosumab, has been developed for the treatment of bone metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22322981", "endSection": "abstract" }, { "offsetInBeginSection": 1819, "offsetInEndSection": 1945, "text": "Denosumab is a neutralizing monoclonal antibody to RANKL and has recently been found to inhibit SRE more effectively than BP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21677475", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1210, "text": "Recently, denosumab, a noncytotoxic IgG2 monoclonal antibody with high affinity for human RANKL, has been demonstrated to significantly prevent clinically relevant increase in pain compared with zoledronic acid across the tumor types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623686", "endSection": "abstract" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1381, "text": "Denosumab, an anti-RANKL monoclonal antibody with proven antiosteoclast activity, may suppress immune responses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21243489", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1653, "text": "We also review unresolved controversies surrounding the management of these conditions by administration of nutritional vitamin D (ergocalciferol and cholecalciferol), vitamin D receptor activators (calcitriol, alphacalcidiol, doxercalciferol), D-mimetics (paricalcitol, maxacalcitol), calcimimetics (cinacalcet), recombinant PTH (teriparatide), and receptor activator of nuclear factor-kappaB ligand modulators (denosumab); compare mortality predictability of PTH and alkaline phosphatase; and examine potential risks of bone disorders and mineral disarrays in CKD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20671739", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 594, "text": "New therapies such as the antibody to RANKL (denosumab) are undergoing phase III clinical testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20703154", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 672, "text": "Receptor activator of nuclear factor kappa B ligand is an important cytokine involved in osteoclast activation; denosumab, a fully human monoclonal antibody to this molecule, has finished a major fracture trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19098925", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 947, "text": "Initials studies have demonstrated that targeting RANK/ RANKL signaling with the fully human monoclonal antibody denosumab prevented skeletal complications in patients with MM and other cancers with bone metastases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18632461", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 963, "text": "A highly specific, fully human antibody against RANKL has been produced (denosumab) that in early studies in humans reduces bone turnover and improves bone density.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16527005", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 802, "text": "Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, shares the pharmacologic attributes of OPG but has a significantly longer half-life that allows less frequent administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16188502", "endSection": "abstract" } ] }, { "body": "List fluorescent reporter proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23741385", "http://www.ncbi.nlm.nih.gov/pubmed/18501461", "http://www.ncbi.nlm.nih.gov/pubmed/14579736", "http://www.ncbi.nlm.nih.gov/pubmed/15258449", "http://www.ncbi.nlm.nih.gov/pubmed/16468989", "http://www.ncbi.nlm.nih.gov/pubmed/18556507", "http://www.ncbi.nlm.nih.gov/pubmed/17407539", "http://www.ncbi.nlm.nih.gov/pubmed/18473954", "http://www.ncbi.nlm.nih.gov/pubmed/23822504", "http://www.ncbi.nlm.nih.gov/pubmed/20532610", "http://www.ncbi.nlm.nih.gov/pubmed/20471991", "http://www.ncbi.nlm.nih.gov/pubmed/12771211", "http://www.ncbi.nlm.nih.gov/pubmed/17646710", "http://www.ncbi.nlm.nih.gov/pubmed/20601526", "http://www.ncbi.nlm.nih.gov/pubmed/23347004", "http://www.ncbi.nlm.nih.gov/pubmed/24128932", "http://www.ncbi.nlm.nih.gov/pubmed/18592415", "http://www.ncbi.nlm.nih.gov/pubmed/18566430", "http://www.ncbi.nlm.nih.gov/pubmed/20429918", "http://www.ncbi.nlm.nih.gov/pubmed/17553146" ], "ideal_answer": [ "Fluorescent and luminescent reporter genes have become popular tools for the real-time monitoring of gene expression in living cells:\ngreen fluorescent protein\nTimer\nred fluorescent protein\nyellow fluorescent protein\nbeta-phycoerythrin\ncoral fluorescent reporter protein\nenhanced green fluorescent reporter protein\nmCherry" ], "exact_answer": [ [ "green fluorescent protein", "Gfp" ], [ "Timer", "DsRed1-E5" ], [ "red fluorescent protein", "dsRed" ], [ "yellow fluorescent protein" ], [ "beta-phycoerythrin" ], [ "coral fluorescent reporter protein" ], [ "enhanced green fluorescent reporter protein" ], [ "mCherry" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017930", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061848", "http://www.uniprot.org/uniprot/GFP_AEQVI", "http://www.uniprot.org/uniprot/LUXY_VIBFI", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005453", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049452", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005455", "http://www.uniprot.org/uniprot/BFP_VIBFI" ], "type": "list", "id": "5523e47f7b523f2123000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Fluorescent Timer, or DsRed1-E5, is a mutant of the red fluorescent protein, dsRed, in which fluorescence shifts over time from green to red as the protein matures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24128932", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 807, "text": "green fluorescent protein (Gfp)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23822504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Characterization of flavin-based fluorescent proteins: an emerging class of fluorescent reporters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741385", "endSection": "title" }, { "offsetInBeginSection": 215, "offsetInEndSection": 256, "text": "Flavin-based fluorescent proteins (FbFPs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741385", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 329, "text": "mCherry was employed as a reporter protein ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23347004", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 749, "text": "yellow fluorescent protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601526", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 295, "text": "red cytoplasmic fluorescent reporter protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20532610", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 510, "text": "red fluorescent reporter protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20532610", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 667, "text": " enhanced green fluorescent reporter protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20471991", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 146, "text": "Fluorescent and luminescent reporter genes have become popular tools for the real-time monitoring of gene expression in living cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20429918", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 715, "text": " fluorescent reporter protein [green fluorescent protein (GFP) and DsRed2]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18592415", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 222, "text": "coral fluorescent reporter protein ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18566430", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 487, "text": "driving a cassette for the enhanced green \"live\" fluorescent reporter protein (eGFP) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18556507", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 290, "text": "GFP as a fluorescent reporter protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18501461", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 154, "text": " protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18473954", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 356, "text": "red fluorescent reporter protein (RFP) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17646710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 35, "text": "The red fluorescent protein eqFP611", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17553146", "endSection": "title" }, { "offsetInBeginSection": 748, "offsetInEndSection": 792, "text": "the green fluorescent reporter protein gene ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17407539", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 447, "text": " red fluorescent reporter protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468989", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 603, "text": "beta-phycoerythrin, a fluorescent reporter protein derived from algae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15258449", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 504, "text": " live-cell fluorescent reporter protein, Timer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14579736", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1204, "text": "red fluorescent reporter protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12771211", "endSection": "abstract" } ] }, { "body": "By which mechanism MutT proteins act against DNA lesions in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23354752", "http://www.ncbi.nlm.nih.gov/pubmed/15850400", "http://www.ncbi.nlm.nih.gov/pubmed/22556419", "http://www.ncbi.nlm.nih.gov/pubmed/9328176", "http://www.ncbi.nlm.nih.gov/pubmed/23463507", "http://www.ncbi.nlm.nih.gov/pubmed/25294823", "http://www.ncbi.nlm.nih.gov/pubmed/11856756", "http://www.ncbi.nlm.nih.gov/pubmed/20345942", "http://www.ncbi.nlm.nih.gov/pubmed/1309939", "http://www.ncbi.nlm.nih.gov/pubmed/10608900", "http://www.ncbi.nlm.nih.gov/pubmed/9603880", "http://www.ncbi.nlm.nih.gov/pubmed/9756871", "http://www.ncbi.nlm.nih.gov/pubmed/23481913", "http://www.ncbi.nlm.nih.gov/pubmed/12717778", "http://www.ncbi.nlm.nih.gov/pubmed/12717453", "http://www.ncbi.nlm.nih.gov/pubmed/21178309", "http://www.ncbi.nlm.nih.gov/pubmed/15475388", "http://www.ncbi.nlm.nih.gov/pubmed/17545288", "http://www.ncbi.nlm.nih.gov/pubmed/7739614", "http://www.ncbi.nlm.nih.gov/pubmed/22092761", "http://www.ncbi.nlm.nih.gov/pubmed/12767940", "http://www.ncbi.nlm.nih.gov/pubmed/9140059", "http://www.ncbi.nlm.nih.gov/pubmed/21111690", "http://www.ncbi.nlm.nih.gov/pubmed/21147134", "http://www.ncbi.nlm.nih.gov/pubmed/23043439", "http://www.ncbi.nlm.nih.gov/pubmed/20880409", "http://www.ncbi.nlm.nih.gov/pubmed/23376345", "http://www.ncbi.nlm.nih.gov/pubmed/23006569", "http://www.ncbi.nlm.nih.gov/pubmed/11892789", "http://www.ncbi.nlm.nih.gov/pubmed/17616589", "http://www.ncbi.nlm.nih.gov/pubmed/10954591", "http://www.ncbi.nlm.nih.gov/pubmed/12531387" ], "ideal_answer": [ "MutT proteins belong to a class of Nudix hydrolases. The common substrate structure for the proteins of the functionally diverse Nudix superfamily is nucleotide-diphosphate-X, where X is a large variety of leaving groups. The activities of Nudix hydrolases usually result in the release of an inorganic phosphate ion or of a product bearing a terminal phosphate moiety. MutT proteins hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the corresponding nucleoside monophosphates and sanitize the nucleotide pool. MutT proteins cleave 8-oxo-dGTP (8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate) at the \u03b1-\u03b2 position; they also cleave 8-oxo-dGTP at the \u03b2-\u03b3 phosphate bond at a rate of 3% of that recorded for hydrolysis at the \u03b1-\u03b2 position. 8-oxo-dGTP induces A to C transversions when misincorporated in DNA opposite to template A. By hydrolyzing 8-oxo-dGTP before their incorporation into DNA, MutT proteins play a critical role in allowing bacteria to avoid A-to-C mutations, which are a hallmark of MutT deficiency. Thus, MutT proteins prevent oxidative DNA lesions, as part of the GO system. Oxidized nucleotides can occur when bacteria are exposed to reactive oxygen species. Also, reactive oxygen species are produced as side products of oxygen utilization, leading to the oxidation of nucleic acids and their precursor nucleotides. Distinct from the Escherichia coli MutT, which hydrolyzes 8-oxo-dGTP and 8-oxo-GTP, the mycobacterial proteins hydrolyze not only 8-oxo-dGTP and 8-oxo-GTP but also dCTP and 5-methyl-dCTP. Moreover, the hydrolysis of 8-oxo-dGTP and 8-oxo-GTP in mycobacteria seems to be catalysed in a two-stage mechanism, since MutT converts these oxidized nucleoside triphosphates to their corresponding nucleoside diphosphates, and not to monophosphates." ], "concepts": [ "http://www.uniprot.org/uniprot/MUTT_PROVU" ], "type": "summary", "id": "5549de44f35db7552600000c", "snippets": [ { "offsetInBeginSection": 946, "offsetInEndSection": 1136, "text": "in addition to the well-characterized hydrolysis of 8-oxo-dGTP at the \u03b1-\u03b2 position, MutT cleaves at the \u03b2-\u03b3 phosphate bond at a rate of 3% of that recorded for hydrolysis at the \u03b1-\u03b2 position", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23481913", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1197, "text": "MutT also catalyzes the hydrolysis of 5-methyl-dCTP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23481913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "The common substrate structure for the functionally diverse Nudix protein superfamily is nucleotide-diphosphate-X, where X is a large variety of leaving groups. The substrate specificity is known for less than 1% of the 29,400 known members. Most activities result in the release of an inorganic phosphate ion or of a product bearing a terminal phosphate moiety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23481913", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 685, "text": "the pathogen is exposed to reactive oxygen species, known to damage dGTP and GTP to 8-oxo-dGTP and 8-oxo-GTP, respectively. Incorporation of the damaged nucleotides in nucleic acids is detrimental to organisms. MutT proteins, belonging to a class of Nudix hydrolases, hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the corresponding nucleoside monophosphates and sanitize the nucleotide pool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463507", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1175, "text": "Here, we characterized MtuMutT1 and Rv1700 proteins of M. tuberculosis. Unlike other MutT proteins, MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP. Rv1700 then converts them to the corresponding nucleoside monophosphates. This observation suggests the presence of a two-stage mechanism of 8-oxo-dGTP/8-oxo-GTP detoxification in mycobacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463507", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1544, "text": "A to C mutations (a hallmark of MutT deficiency)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Reactive oxygen species are produced as side products of oxygen utilization and can lead to the oxidation of nucleic acids and their precursor nucleotides. Among the various oxidized bases, 8-oxo-7,8-dihydroguanine seems to be the most critical during the transfer of genetic information because it can pair with both cytosine and adenine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376345", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 618, "text": "oxidized form of GMP (8-oxo-GMP) formed by the oxidation of GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376345", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1214, "text": "The 8-oxo-GTP produced in this way and by the oxidation of GTP can be used for RNA synthesis. This misincorporation is prevented by MutT protein, which has the potential to cleave 8-oxo-GTP as well as 8-oxo-GDP to 8-oxo-GMP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376345", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 429, "text": "By hydrolyzing the oxidized guanine nucleotides before their incorporation into nucleic acids, MutT proteins play a critical role in allowing organisms to avoid their deleterious effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354752", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 911, "text": "Distinct from the Escherichia coli MutT, which hydrolyzes 8-oxo-dGTP and 8-oxo-GTP, the mycobacterial proteins hydrolyze not only 8-oxo-dGTP and 8-oxo-GTP but also dCTP and 5-methyl-dCTP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354752", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1404, "text": "A-to-C mutations (a hallmark of MutT deficiency)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 436, "text": "Reactive oxygen species induce oxidative damage in DNA precursors, i.e. dNTPs, leading to point mutations upon incorporation. Escherichia coli mutT strains, deficient in the activity hydrolysing 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), display more than a 100-fold higher spontaneous mutation frequency over the wild-type strain. 8-oxo-dGTP induces A to C transversions when misincorporated opposite template A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23043439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Prevention and correction of oxidative DNA lesions in Pseudomonas aeruginosa is ensured by the DNA oxidative repair system (GO). Single inactivation of mutT, mutY and mutM involved in GO led to elevated mutation rates (MRs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22092761", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 845, "text": "the GO system (mutM, mutY and mutT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20880409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Human MTH1 and Escherichia coli MutT proteins hydrolyze 7, 8-dihydro-8-oxo-dGTP (8-oxo-dGTP) to monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine into nascent DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10608900", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 972, "text": "Unlike other MutT proteins, MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463507", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 681, "text": "MutT proteins, belonging to a class of Nudix hydrolases, hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the corresponding nucleoside monophosphates and sanitize the nucleotide pool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463507", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 428, "text": "By hydrolyzing the oxidized guanine nucleotides before their incorporation into nucleic acids, MutT proteins play a critical role in allowing organisms to avoid their deleterious effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "MutT-related proteins, including the Escherichia coli MutT and human MutT homologue 1 (MTH1) proteins, degrade 8-oxo- 7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP) to a monophosphate, thereby preventing mutations caused by the misincorporation of 8-oxoguanine into DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12717453", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 943, "text": "In mutator strains lacking MutT and/or MutM proteins, 8-oxoguanine of DNA increased to a concentration expected from the increased rate of mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7739614", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 703, "text": "coli strains with mutations in genes responsible for the repair of DNA containing oxidative lesions (mutY, mutS, mutM, mutT, nth) were less resistant to AgNP than wild type strains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23006569", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1036, "text": "MutT and MutY proteins, when active, protect bacteria from mutations induced by 8-oxoG lesions in DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12717778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "MutT-related proteins degrade 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), a mutagenic substrate for DNA synthesis, in the nucleotide pool, thereby preventing DNA replication errors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12767940", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 708, "text": "coli strains with mutations in genes responsible for the repair of DNA containing oxidative lesions (mutY, mutS, mutM, mutT, nth) were less resistant to AgNP than wild type strains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23006569", "endSection": "abstract" } ] }, { "body": "Was tamoxifen tested for treatment of glioma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9773800", "http://www.ncbi.nlm.nih.gov/pubmed/16710748", "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "http://www.ncbi.nlm.nih.gov/pubmed/9815790", "http://www.ncbi.nlm.nih.gov/pubmed/12712458", "http://www.ncbi.nlm.nih.gov/pubmed/15022287", "http://www.ncbi.nlm.nih.gov/pubmed/12680157", "http://www.ncbi.nlm.nih.gov/pubmed/8837815", "http://www.ncbi.nlm.nih.gov/pubmed/19810975", "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "http://www.ncbi.nlm.nih.gov/pubmed/10797257", "http://www.ncbi.nlm.nih.gov/pubmed/9266439", "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "http://www.ncbi.nlm.nih.gov/pubmed/21353747" ], "ideal_answer": [ "Yes, tamoxifen was tested for glioma treatment. However, clinical efficacy of tamoxifen in glioma patients remains unclear and should be tested in further studies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013629", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005910" ], "type": "yesno", "id": "56c0968def6e394741000026", "snippets": [ { "offsetInBeginSection": 1694, "offsetInEndSection": 1892, "text": "Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21353747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "endSection": "title" }, { "offsetInBeginSection": 769, "offsetInEndSection": 956, "text": "In this study, in which tamoxifen was used in conjunction with radiotherapy, progression free survival was shown to be less good when compared with historical data HR = 3.1 (CI: 1.7-5.7).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1196, "text": "The addition of high-dose tamoxifen, although well tolerated, confers no clinical benefit to patients treated with diffuse intrinsic pontine glioma treated with standard radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "endSection": "abstract" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1696, "text": "CONCLUSIONS: Carboplatin and high dose tamoxifen has similar response rates to other regimens for recurrent malignant gliomas and are probably equivalent to those found using tamoxifen as monotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16710748", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1793, "text": "CONCLUSIONS: Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15022287", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 288, "text": "Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been used in the treatment of malignant gliomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12712458", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1028, "text": "Considering these facts, polyethylene-glycol-liposomal doxorubicin with and without tamoxifen was evaluated within two sequential Phase II trials performed at our institution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19810975", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 369, "text": "In a parallel phase-II-study investigating post-operative treatment with tamoxifen (TAM), carboplatin and radiation therapy for glioblastomas, 16 of 49 patients (33%) showed multifocal recurrence, which developed after a mean of 46 weeks, raising the question of an association with therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10797257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1455, "text": "CONCLUSION: This treatment combination produced no significant change in the overall poor prognosis of these patients. Most tumors responded initially to treatment but recurred as the study progressed. A minority of patients seemed to benefit from the extended use of TX. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 447, "text": "Tamoxifen, a protein kinase C inhibitor when administered in high dosages, is currently being used as an adjuvant in the treatment of patients with malignant gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8837815", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1375, "text": "We present a patient with a recurrent malignant glioma who was continued on high dose tamoxifen despite radiologic documented doubling of the tumor size and who eventually showed a delayed response to this agent nine months after initiation of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9266439", "endSection": "abstract" }, { "offsetInBeginSection": 1707, "offsetInEndSection": 1956, "text": "The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9815790", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Phase I clinical trial assessing temozolomide and tamoxifen with concomitant radiotherapy for treatment of high-grade glioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21353747", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Prolonged treatment with biologic agents for malignant glioma: a case study with high dose tamoxifen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9266439", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Tamoxifen as a potential treatment of glioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9773800", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 441, "text": "We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 440, "text": "We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 555, "text": "We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 440, "text": "Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered. Propylthiouracil was used to induce chemical hypothyroidism in 22 patients with recurrent glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12680157", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 441, "text": "Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 341, "text": "Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12680157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "title" }, { "offsetInBeginSection": 290, "offsetInEndSection": 441, "text": "We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1330, "text": "The subsequent in vitro testing of the tumor that was removed after the recurrence of tumor (22 months after the initiation of tamoxifen) revealed loss of sensitivity to tamoxifen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8837815", "endSection": "abstract" }, { "offsetInBeginSection": 1471, "offsetInEndSection": 1720, "text": "The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9524096", "endSection": "abstract" } ] }, { "body": "Which transcription factors are known as the four (4) \"Yamanaka factors\" that have been used to create induced pluripotent stem cells (iPSCs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21839145", "http://www.ncbi.nlm.nih.gov/pubmed/23149977", "http://www.ncbi.nlm.nih.gov/pubmed/23704989", "http://www.ncbi.nlm.nih.gov/pubmed/23272148", "http://www.ncbi.nlm.nih.gov/pubmed/24706886", "http://www.ncbi.nlm.nih.gov/pubmed/23658991", "http://www.ncbi.nlm.nih.gov/pubmed/23939864", "http://www.ncbi.nlm.nih.gov/pubmed/23266889", "http://www.ncbi.nlm.nih.gov/pubmed/23104133", "http://www.ncbi.nlm.nih.gov/pubmed/23166588" ], "ideal_answer": [ "Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM). In particular, the mechanisms how the Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) directly drive reprogramming and which additional components are involved are still not yet understood.", "Through the ectopic expression of four transcription factors, Oct4, Klf4, Sox2 and cMyc, human somatic cells can be converted to a pluripotent state, generating so-called induced pluripotent stem cells (iPSCs)(1-4). Delivery of the transcription factors Oct4, Klf4, Sox2 and c-Myc via integrating viral vectors has been widely employed to generate induced pluripotent stem cell (iPSC) lines from both normal and disease-specific somatic tissues, providing an invaluable resource for medical research and drug development. ", "Through the ectopic expression of four transcription factors, Oct4, Klf4, Sox2 and cMyc, human somatic cells can be converted to a pluripotent state, generating so-called induced pluripotent stem cells (iPSCs)(1-4).Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM), but the mechanisms underlying this reprogramming remain poorly understood." ], "exact_answer": [ [ "Oct4", "Oct 3/4" ], [ "Sox2" ], [ "Klf4" ], [ "c-Myc" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057026", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039904" ], "type": "list", "id": "54fb5720d176fff445000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The recently established reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by Takahashi and Yamanaka represents a valuable tool for future therapeutic applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23939864", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 453, "text": "In particular, the mechanisms how the Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) directly drive reprogramming and which additional components are involved are still not yet understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23939864", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 638, "text": "Here we show that Yamanaka factors (OCT4, SOX2, MYC, and KLF4)-expressing EV can also reprogram adult peripheral blood mononuclear cells (PBMNCs) into pluripotency, yet at a very low efficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704989", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 941, "text": "The CytoTune\u2122-iPS Reprogramming Kit contains four SeV-based reprogramming vectors, each capable of expressing one of the four Yamanaka factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and are optimized for generating iPSCs from human somatic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Delivery of the transcription factors Oct4, Klf4, Sox2 and c-Myc via integrating viral vectors has been widely employed to generate induced pluripotent stem cell (iPSC) lines from both normal and disease-specific somatic tissues, providing an invaluable resource for medical research and drug development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272148", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 1031, "text": "We demonstrate that residual expression of the Yamanaka factors prevents iPSCs from acquiring the transcriptional program exhibited by embryonic stem cells (ESCs) and that the expression profiles of iPSCs generated with and without c-Myc are indistinguishable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM), but the mechanisms underlying this reprogramming remain poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23266889", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 889, "text": "We also discovered that HMGA1 enhances cellular reprogramming of somatic cells to iPSCs together with the Yamanaka factors (OCT4, SOX2, KLF4, cMYC - OSKM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Through the ectopic expression of four transcription factors, Oct4, Klf4, Sox2 and cMyc, human somatic cells can be converted to a pluripotent state, generating so-called induced pluripotent stem cells (iPSCs)(1-4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23149977", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 720, "text": "We have shown the generation of transgene-free human iPSCs from patients with different lung diseases using a single excisable polycistronic lentiviral Stem Cell Cassette (STEMCCA) encoding the Yamanaka factors(6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23149977", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1050, "text": "These iPSCs were established in a feeder-free system by lentiviral transduction of the Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Induced pluripotent stem cells (iPSCs) are created by the reprogramming of somatic cells via overexpression of certain transcription factors, such as the originally described Yamanaka factors: Oct4, Sox2, Klf4, and c-Myc (OSKM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24706886", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 638, "text": "iPSC production was first achieved by transducing, with the use of retroviral vectors, four specific transcription factors: Oct4, Klf4, Sox2 and c-Myc (OKSM), into primary cells in culture Takahashi and Yamanaka, (Cell 126(4):663-676, 2006)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104133", "endSection": "abstract" } ] }, { "body": "What is the role of anhedonia in coronary disease patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20439829", "http://www.ncbi.nlm.nih.gov/pubmed/19430927", "http://www.ncbi.nlm.nih.gov/pubmed/18069998", "http://www.ncbi.nlm.nih.gov/pubmed/20105694", "http://www.ncbi.nlm.nih.gov/pubmed/19932820", "http://www.ncbi.nlm.nih.gov/pubmed/21082266", "http://www.ncbi.nlm.nih.gov/pubmed/22923700", "http://www.ncbi.nlm.nih.gov/pubmed/22345679", "http://www.ncbi.nlm.nih.gov/pubmed/21491341" ], "ideal_answer": [ "Anhedonia is associated with poor prognosis in patients with coronary disease. Namely, in patients with coronary disease, anhedonia was associated with increased mortality, greater risk for major cardiac event, impaired physical health status, more cardiac symptoms, more feelings of disability. These associations were independent from clinical and demographic factors." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059445", "http://www.disease-ontology.org/api/metadata/DOID:3393", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003327", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324" ], "type": "summary", "id": "514cd15ad24251bc05000067", "snippets": [ { "offsetInBeginSection": 1023, "offsetInEndSection": 1654, "text": "Reduced positive affect and depression/anxiety were associated with poor prognosis, but reduced positive affect was the only independent predictor of events. The incidence of death/MI in adequate versus reduced positive affect patients was 4% (29/663) vs. 11% (23/211); HR = 2.55 (95% CI 1.46-4.34, P = 0.001), adjusting for clinical variables. Reduced positive affect and diabetes were independent prognostic factors, and patients with one (HR = 2.84, 95% CI 1.58-5.10) or both (HR = 5.61, 95% CI 2.25-13.99) of these factors had a higher risk when compared with nondiabetic patients with adequate positive affect, P < or = 0.003.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18069998", "endSection": "sections.0" }, { "offsetInBeginSection": 1668, "offsetInEndSection": 1814, "text": "Reduced positive affect independently predicted death/MI following stent implantation, and improved risk stratification above and beyond diabetes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18069998", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Reduced positive affect (anhedonia) predicts major clinical events following implantation of coronary-artery stents.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18069998", "endSection": "title" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1433, "text": "t follow-up, there were 176 clinical events (36 deaths, 8 MIs, 58 ACS, 55 hospital readmissions, 19 heart failures). Dimensional anhedonia and depression were associated with poor prognosis, but anhedonia was the only predictor of severe cardiac events and clinical events after adjusting for demographic and clinical variables.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19932820", "endSection": "sections.0" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1599, "text": "Contrary to depression, categorical anhedonia (PAS >23) was an independent and significant predictor of severe cardiac events after adjusting for clinical variables.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19932820", "endSection": "sections.0" }, { "offsetInBeginSection": 1600, "offsetInEndSection": 1729, "text": "The incidence of death/MI in hedonics vs anhedonics was 11.1% vs 22.1% (hazard ratio = 2.18; 95% confidence interval, 1.11-4.26).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19932820", "endSection": "sections.0" }, { "offsetInBeginSection": 1743, "offsetInEndSection": 1858, "text": "Dimensional and categorical anhedonias predicted independently severe cardiac events and clinical events after ACS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19932820", "endSection": "sections.0" }, { "offsetInBeginSection": 444, "offsetInEndSection": 752, "text": "Only depressive symptoms of fatigue-sadness predicted prognosis in univariate (hazard ratio [HR]=1.8, 95% CI 1.1-3.0, P=.025) and multivariate analysis (HR=1.8, 95% CI 1.1-2.9, P=.025). Symptoms of anhedonia (HR=1.6, 95% CI 0.9-2.8, P=.102) and depressive cognitions (HR=1.3, 95% CI 0.7-2.2, P=.402) did not.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20105694", "endSection": "sections.0" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1642, "text": "Controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16-2.14; P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439829", "endSection": "sections.0" }, { "offsetInBeginSection": 1643, "offsetInEndSection": 1786, "text": "Anhedonia continued to significantly predict outcomes (P < .05) when additionally controlling for MDE diagnosis or depressive symptom severity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439829", "endSection": "sections.0" }, { "offsetInBeginSection": 1945, "offsetInEndSection": 2091, "text": "Anhedonia identifies risk of MACE and ACM beyond that of established medical prognostic indicators, including MDE and depressive symptom severity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439829", "endSection": "sections.0" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1162, "text": "The incidence of mortality in anhedonic patients was 22.7% (65/286) vs. 13.2% (121/920) in non-anhedonic patients (HR = 1.66, 95% CI [1.19-2.32], p = 0.003).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345679", "endSection": "sections.0" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1296, "text": "Cumulative hazard functions were significantly different for anhedonic vs. non-anhedonic patients (log-rank \u03c7(2) = 16.61, p < 0.001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345679", "endSection": "sections.0" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1535, "text": "n multivariable analysis, anhedonia remained independently associated with all-cause mortality (HR = 1.51, 95% CI [1.03-2.22], p = 0.036), after adjusting for socio-demographics, clinical characteristics, and negative and relaxed affect.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345679", "endSection": "sections.0" }, { "offsetInBeginSection": 1549, "offsetInEndSection": 1696, "text": "Anhedonia was independently associated with a 1.5-fold increased risk for all-cause mortality in patients who survived the first 6 months post-PCI.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345679", "endSection": "sections.0" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1600, "text": "Depressive symptoms related to lack of enjoyment or pleasure and physical or cognitive slowing, as measured by the HADS-D, predicted all-cause mortality at 8 years ACS patients, whereas other depressive and anxiety symptoms did not.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22923700", "endSection": "sections.0" } ] }, { "body": "What is the clinical value of naltrexone in Parkinson's disease patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/152622", "http://www.ncbi.nlm.nih.gov/pubmed/11254789", "http://www.ncbi.nlm.nih.gov/pubmed/22426027", "http://www.ncbi.nlm.nih.gov/pubmed/7969211", "http://www.ncbi.nlm.nih.gov/pubmed/23634190", "http://www.ncbi.nlm.nih.gov/pubmed/25037206" ], "ideal_answer": [ "Naltrexone does not improve clinical features, including motor function, in Parkinson's disease patients. Naltrexone was shown to be effective for treatment of pathological gambling in Parkinson's disease patients." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14330", "http://www.biosemantics.org/jochem#4249647" ], "type": "summary", "id": "55033064e9bde69634000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Opioid antagonist naltrexone for the treatment of pathological gambling in Parkinson disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426027", "endSection": "title" }, { "offsetInBeginSection": 535, "offsetInEndSection": 685, "text": "These patients responded poorly to serotonin reuptake inhibitors, whereas treatment with opioid antagonist naltrexone resulted in the remission of PG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426027", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 948, "text": "CONCLUSIONS: The opioid antagonist naltrexone could be an effective option for the treatment of PG in PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426027", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 350, "text": "No improvement in the clinical features of either disorder was noted", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/152622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Naltrexone, an opiate antagonist, fails to modify motor symptoms in patients with Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7969211", "endSection": "title" }, { "offsetInBeginSection": 415, "offsetInEndSection": 529, "text": "Naltrexone as compared with placebo did not demonstrate any significant change in motor function in either group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7969211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Naltrexone, an opiate antagonist, fails to modify motor symptoms in patients with Parkinsons disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7969211", "endSection": "title" } ] }, { "body": "What is the efficacy of oxaliplatin monotherapy in the management of colorectal cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15879624", "http://www.ncbi.nlm.nih.gov/pubmed/16702162", "http://www.ncbi.nlm.nih.gov/pubmed/9704726", "http://www.ncbi.nlm.nih.gov/pubmed/10408744", "http://www.ncbi.nlm.nih.gov/pubmed/18094427" ], "ideal_answer": [ "Oxaliplatin is a promising treatment option for patients with metastatic colorectal cancer. It appears to be particularly advantageous (in terms of response rate and duration of progression-free survival) when used in combination with fluorouracil/calcium folinate as both a first- and second-line option, although preliminary studies have failed to show any survival advantage over fluorouracil/calcium folinate alone. Promising results have been found in studies of the drug as monotherapy, and oxaliplatin may also prove useful in the neoadjuvant setting in patients with unresectable liver metastases; however, data are limited at present" ], "concepts": [ "http://www.biosemantics.org/jochem#4278407", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015179", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003123", "http://www.disease-ontology.org/api/metadata/DOID:9256" ], "type": "summary", "id": "5541297f182542114d000001", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 125, "text": " Oxaliplatin, a platinum compound, has been commonly used around the world for treating advanced colorectal cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702162", "endSection": "abstract" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1672, "text": "The oxaliplatin monotherapy dose schedule of 130 mg/m(2) every 3 weeks, recommended worldwide, is acceptable for Japanese patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702162", "endSection": "abstract" }, { "offsetInBeginSection": 2188, "offsetInEndSection": 2830, "text": "oxaliplatin is a promising treatment option for patients with metastatic colorectal cancer. It appears to be particularly advantageous (in terms of response rate and duration of progression-free survival) when used in combination with fluorouracil/calcium folinate as both a first- and second-line option, although preliminary studies have failed to show any survival advantage over fluorouracil/calcium folinate alone. Promising results have been found in studies of the drug as monotherapy, and oxaliplatin may also prove useful in the neoadjuvant setting in patients with unresectable liver metastases; however, data are limited at present", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408744", "endSection": "abstract" }, { "offsetInBeginSection": 1394, "offsetInEndSection": 1587, "text": "This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9704726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9704726", "endSection": "abstract" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1539, "text": "This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9704726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Capecitabine and oxaliplatin are both effective and well-tolerated monotherapies for the treatment of advanced colorectal cancer (CRC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15879624", "endSection": "abstract" } ] }, { "body": "Are there any animal models for Niemann-Pick C1 disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24044630", "http://www.ncbi.nlm.nih.gov/pubmed/22325094", "http://www.ncbi.nlm.nih.gov/pubmed/19875890", "http://www.ncbi.nlm.nih.gov/pubmed/20864542", "http://www.ncbi.nlm.nih.gov/pubmed/22404083", "http://www.ncbi.nlm.nih.gov/pubmed/12297829", "http://www.ncbi.nlm.nih.gov/pubmed/22198570", "http://www.ncbi.nlm.nih.gov/pubmed/16940355", "http://www.ncbi.nlm.nih.gov/pubmed/19458211", "http://www.ncbi.nlm.nih.gov/pubmed/22048958", "http://www.ncbi.nlm.nih.gov/pubmed/20581737", "http://www.ncbi.nlm.nih.gov/pubmed/23843985", "http://www.ncbi.nlm.nih.gov/pubmed/21176403", "http://www.ncbi.nlm.nih.gov/pubmed/21995947", "http://www.ncbi.nlm.nih.gov/pubmed/20607864", "http://www.ncbi.nlm.nih.gov/pubmed/17216601" ], "ideal_answer": [ "Yes, murine models of Niemann-Pick type C disease (NPC) exist. They are either homozygous or heterozygous NPC1-deficient [NPC1 (-/-)]/ [NPC1 (+/-)] mouse models." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/NPC1_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.disease-ontology.org/api/metadata/DOID:14504", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004195", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009542", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023421" ], "type": "yesno", "id": "532f0ca1d6d3ac6a3400002f", "snippets": [ { "offsetInBeginSection": 462, "offsetInEndSection": 528, "text": "Several animal models were used to analyze the impaired pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24044630", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 468, "text": "We investigated components of the surfactant system in both NPC1 mutant mice and felines and in NPC2 mutant mice near the end of their expected life span. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843985", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 383, "text": "Thus far, studies of NPC mice have been performed mainly to study the brain and neurodegeneration, because degeneration in the brain was known as the primary cause of death in NPC mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22404083", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 288, "text": "the NPC1(-/-) mouse is available serving as an appropriate animal model of the human disease,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22325094", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 481, "text": "o examine the onset and progression of neuropathological insults in NPC we have systematically examined the CNS of a mouse model of NPC1 (Npc1(-/-) mice) at different stages of the disease course.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22198570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22048958", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 578, "text": "Niemann-Pick type C1-deficient mice, which accumulate intracellular free cholesterol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21995947", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 453, "text": "hUCB-MSCs were transplanted into the hippocampus of NPC mice in the early asymptomatic stage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21176403", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 152, "text": " Niemann Pick type C1 mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21176403", "endSection": "title" }, { "offsetInBeginSection": 380, "offsetInEndSection": 466, "text": "Three mouse models of glycosphingolipid storage diseases, namely Niemann-Pick type C1,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20864542", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 879, "text": "Npc1(-/-) mice, a well-established model of NPC pathology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20607864", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 391, "text": "murine model of this disease, the npc1 mouse,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581737", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 457, "text": "NPC1 (Niemann-Pick type C1) knock-out mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458211", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 305, "text": "We have made transgenic mice which express the Npc1 protein exclusively in fibrillary astrocytes, using the glial fibrillary acidic protein (GFAP) promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19875890", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 742, "text": "homozygous affected (NPC1(-/-)) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17216601", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 967, "text": "heterozygous (NPC1(+/-)) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17216601", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1118, "text": "npc1(-/-) mice,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940355", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 335, "text": "npc1(-/-) mouse model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940355", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 466, "text": "A murine model of Niemann-Pick type C disease (NPC), the NPC1-deficient [NPC1 (-/-)] mouse, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12297829", "endSection": "abstract" } ] }, { "body": "Which type of genes are modulated by SATB1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15371550", "http://www.ncbi.nlm.nih.gov/pubmed/16034473", "http://www.ncbi.nlm.nih.gov/pubmed/21841785" ], "ideal_answer": [ "Lack of effector T cell (T(eff) cell) function and gain of suppressive activity by T(reg) cells are dependent on the transcriptional program induced by Foxp3. Here we report that repression of SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells. Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines. At an Associative t-test threshold of P", "Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation", "Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines." ], "exact_answer": [ "it supresses cell cytokines and differentiation genes" ], "concepts": [ "http://www.uniprot.org/uniprot/SATB1_HUMAN", "http://www.uniprot.org/uniprot/SATB1_MOUSE" ], "type": "factoid", "id": "56fcf1b8cf1c325851000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "title" }, { "offsetInBeginSection": 284, "offsetInEndSection": 424, "text": "SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 616, "text": "Foxp3, acting as a transcriptional repressor, directly suppressed the SATB1 locus and indirectly suppressed it through the induction of microRNAs that bound the SATB1 3' untranslated region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 806, "text": "Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1298, "text": "Consistent with previous reports in a non-superantigen in vivo anergy model, mRNA for CD18 and the transcription factor Satb1 (special AT-rich-binding protein 1) was increased in SEB-energized T cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034473", "endSection": "abstract" } ] }, { "body": "Does HER2 under-expression lead to favorable response to trastuzumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22711713", "http://www.ncbi.nlm.nih.gov/pubmed/20392785", "http://www.ncbi.nlm.nih.gov/pubmed/23082154", "http://www.ncbi.nlm.nih.gov/pubmed/19606230", "http://www.ncbi.nlm.nih.gov/pubmed/12503030", "http://www.ncbi.nlm.nih.gov/pubmed/21709140", "http://www.ncbi.nlm.nih.gov/pubmed/18534031", "http://www.ncbi.nlm.nih.gov/pubmed/19920112", "http://www.ncbi.nlm.nih.gov/pubmed/19435924", "http://www.ncbi.nlm.nih.gov/pubmed/22580986", "http://www.ncbi.nlm.nih.gov/pubmed/11148461", "http://www.ncbi.nlm.nih.gov/pubmed/19624808", "http://www.ncbi.nlm.nih.gov/pubmed/22658319" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00072", "o": "Trastuzumab" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0728747", "o": "http://linkedlifedata.com/resource/umls/label/A10771788" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10771788", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1545807", "o": "trastuzumab" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8438296", "o": "TRASTUZUMAB" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A1545806", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "No, trastuzumab is effective only in cancers where Her2 is over-expessed." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018734", "http://www.disease-ontology.org/api/metadata/DOID:0060079", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020869", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010467", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0038128", "http://www.biosemantics.org/jochem#4002084", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005176", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005786", "http://www.disease-ontology.org/api/metadata/DOID:0060080" ], "type": "yesno", "id": "51542eacd24251bc05000084", "snippets": [ { "offsetInBeginSection": 211, "offsetInEndSection": 331, "text": "over-expression of HER2 is reported in approximately 20% of gastric tumours, challenging the use of targeted therapies. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22711713", "endSection": "sections.0" }, { "offsetInBeginSection": 526, "offsetInEndSection": 802, "text": "In patients with advanced gastric or gastro-oesophageal junction cancer, addition of trastuzumab to chemotherapy significantly improved overall survival compared with chemotherapy alone. Addition of trastuzumab to chemotherapy did not increase the incidence of adverse events.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22711713", "endSection": "sections.0" }, { "offsetInBeginSection": 348, "offsetInEndSection": 408, "text": "treatment of HER2-overexpressing breast cancer: trastuzumab,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22658319", "endSection": "sections.0" }, { "offsetInBeginSection": 173, "offsetInEndSection": 354, "text": "Trastuzumab has demonstrated clinical activity in several types of HER2-overexpressing epithelial tumors, such as breast and metastatic gastric or gastroesophageal junction cancer. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22580986", "endSection": "sections.0" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1817, "text": "An example is the established benefit of trastuzumab as adjuvant therapy for breast cancer; a clear definition of HER2-positivity and the assay reproducibility have, however, remained unanswered. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20392785", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 136, "text": "Trastuzumab is a monoclonal antibody targeted to the Her2 receptor and approved for treatment of Her2-positive breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19920112", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "Human epidermal growth factor receptor 2 (HER2/neu) is an important target for the treatment of the breast cancers in which it is overexpressed. However, no approved anti-HER2/neu therapy is available for the majority of breast cancer patients, who express HER2/neu at low levels (with scores of 1+ or 2+/fluorescence in situ hybridization-negative).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19435924", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 146, "text": "The humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) is useful in the treatment of ErbB2-overexpressing breast cancers,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12503030", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "HercepTestTM (DAKO A/S, Glostrup, Denmark) is an immunohistochemical assay that detects HER2/neu gene products, and evaluates the overexpression status of the HER2/neu protein in determining eligibility for the Trastuzumab (HerceptinR, Genentech, San Francisco, CA, USA) therapy. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11148461", "endSection": "sections.0" } ] }, { "body": "Which are the most abundant human lincRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9886562", "http://www.ncbi.nlm.nih.gov/pubmed/22840402", "http://www.ncbi.nlm.nih.gov/pubmed/22718948", "http://www.ncbi.nlm.nih.gov/pubmed/17270048", "http://www.ncbi.nlm.nih.gov/pubmed/12490325", "http://www.ncbi.nlm.nih.gov/pubmed/22840393", "http://www.ncbi.nlm.nih.gov/pubmed/22916204", "http://www.ncbi.nlm.nih.gov/pubmed/23129630", "http://www.ncbi.nlm.nih.gov/pubmed/8785513", "http://www.ncbi.nlm.nih.gov/pubmed/23243023", "http://www.ncbi.nlm.nih.gov/pubmed/20459797", "http://www.ncbi.nlm.nih.gov/pubmed/24035497", "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "http://www.ncbi.nlm.nih.gov/pubmed/22684254", "http://www.ncbi.nlm.nih.gov/pubmed/23073843" ], "ideal_answer": [ "MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) locus is misregulated in many human cancers and produces an abundant long nuclear-retained noncoding RNA. MALAT/NEAT2 highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution. H19 large intergenic non-coding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extra-embryonic cell lineages, yet its physiological function is unknown. Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2." ], "exact_answer": [ [ "MALAT1", "MALAT-1", "NEAT2" ], [ "NEAT1" ], [ "H19" ], [ "XIST" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085" ], "type": "list", "id": "5363bad27d100faa0900000e", "snippets": [ { "offsetInBeginSection": 630, "offsetInEndSection": 817, "text": "One abundant such RNA, ci-ankrd52, largely accumulates to its sites of transcription, associates with elongation Pol II machinery, and acts as a positive regulator of Pol II transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035497", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 279, "text": "long noncoding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), also known as MALAT-1 or NEAT2 (nuclear-enriched abundant transcript 2), is a highly conserved nuclear noncoding RNA (ncRNA) and a predictive marker for metastasis development in lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23243023", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 629, "text": "Because viruses borrow molecular mechanisms from their hosts, we searched highly abundant human long-noncoding RNAs and identified putative ENE-like structures in metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and multiple endocrine neoplasia-\u03b2 (MEN\u03b2) RNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23129630", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 173, "text": "MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) locus is misregulated in many human cancers and produces an abundant long nuclear-retained noncoding RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23073843", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 418, "text": "Many long noncoding RNAs (lncRNAs) appear to have epigenetic regulatory function in humans, including HOTAIR and XIST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22916204", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 166, "text": "metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 439, "text": "It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "endSection": "abstract" }, { "offsetInBeginSection": 1203, "offsetInEndSection": 1313, "text": "Thus, loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 250, "text": "bundant expression of the long noncoding (lnc) PAN (polyadenylated nuclear) RNA by the human oncogenic gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) depends on a cis-element called the expression and nuclear retention element (ENE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22840393", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 162, "text": "alat1 is an abundant long, noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22718948", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 427, "text": "Malat1 (metastasis associated lung adenocarcinoma transcript 1) is among the most abundant and highly conserved lncRNAs, and it exhibits an uncommon 3'-end processing mechanism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22840402", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 249, "text": "H19 large intergenic non-coding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extra-embryonic cell lineages, yet its physiological function is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22684254", "endSection": "abstract" }, { "offsetInBeginSection": 1643, "offsetInEndSection": 1838, "text": "Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17270048", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 149, "text": "19, which is one of the most abundantly expressed imprinted genes during mammalian embryonic and foetal development, has been cloned from a ruminant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12490325", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 974, "text": "H19 mRNA is highly abundant in most ovine embryonic and foetal tissues of mesodermal and endodermal origins but was not detected in tissues of ectodermal origin such as the trophectoderm and the foetal brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12490325", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1264, "text": "Abundant expression of H19 was evident in fetal bladder but was absent in normal adult bladder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886562", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1927, "text": "urthermore, we discuss results showing an abundant expression of H19 gene in some adenocarcinomas of bad prognosis, in the context of the otherwise established tumor-suppressor role of this gene, or the strictly controlled gene dosage, which could be overridden in these particular cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8785513", "endSection": "abstract" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1291, "text": "One of the first lncRNA genes discovered was MALAT1, the metastasis-associated lung adenocarcinoma transcript 1,21 later also referred to as NEAT2 for nuclear-enriched abundant transcript 2. MALAT1 is highly abundant and is expressed in many healthy organs, most strongly in pancreas and lung", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "endSection": "sections.0" } ] }, { "body": "Which is the molecular function of the protein CCDC40?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25493340", "http://www.ncbi.nlm.nih.gov/pubmed/25186273", "http://www.ncbi.nlm.nih.gov/pubmed/23234452", "http://www.ncbi.nlm.nih.gov/pubmed/23402890", "http://www.ncbi.nlm.nih.gov/pubmed/22693285", "http://www.ncbi.nlm.nih.gov/pubmed/25802884", "http://www.ncbi.nlm.nih.gov/pubmed/23255504", "http://www.ncbi.nlm.nih.gov/pubmed/22499950", "http://www.ncbi.nlm.nih.gov/pubmed/21131974" ], "ideal_answer": [ "The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation and mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms." ], "type": "summary", "id": "56d2adc5f22319765a000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal recessive disorder that results from functional and ultrastructural abnormalities of motile cilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25802884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Primary ciliary dyskinesia (PCD) is a rare genetic disorder leading to recurrent respiratory tract infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25186273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25186273", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23255504", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Human cilia were once thought merely to be important in respiratory mucociliary clearance, with primary ciliary dyskinesia (PCD) the sole manifestation of ciliary dysfunction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23234452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21131974", "endSection": "title" }, { "offsetInBeginSection": 1505, "offsetInEndSection": 1612, "text": "CCDC39 and CCDC40 mutations represent the major cause of PCD with IDA defects and axonemal disorganisation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693285", "endSection": "abstract" } ] }, { "body": "Can administration of the thyrotropin releasing hormone reduce fatigue in cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21947558", "http://www.ncbi.nlm.nih.gov/pubmed/23387883", "http://www.ncbi.nlm.nih.gov/pubmed/19761698" ], "ideal_answer": [ "yes, in cancer patients, thyrotropin releasing hormone (TRH) administration was associated with significant improvement in cancer related fatigue levels as measured by the Visual Analog Scale-Energy, fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F. TRH administration was safe and tolerable in the treatment of cancer-related with a positive impact on quality of life, suggesting the need for further studies investigating TRH for treatment of fatigue in cancer patients." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/TRH_NOTVI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013973", "http://www.uniprot.org/uniprot/TRHA_XENLA", "http://www.uniprot.org/uniprot/TRH_BOMOR", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.uniprot.org/uniprot/TRH_PIG", "http://www.uniprot.org/uniprot/TRH_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005221" ], "type": "yesno", "id": "5314d0e4dae131f84700000e", "snippets": [ { "offsetInBeginSection": 1228, "offsetInEndSection": 1482, "text": "TRH administration was associated with significant improvement (p < 0.05) in fatigue levels as measured by the Visual Analog Scale-Energy (VAS-E), was associated with significant (p < 0.05) improvement in sleep disturbances and improved quality of life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23387883", "endSection": "abstract" }, { "offsetInBeginSection": 1601, "offsetInEndSection": 1727, "text": "This decrease in CRP level with TRH administration was associated with improvement in energy levels as measured by the VAS-E. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23387883", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 483, "text": "In the present pilot, randomized, placebo-controlled, crossover study, we investigated the efficacy and safety of TRH as a treatment for CF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947558", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1289, "text": "TRH administration was associated with significant improvement in fatigue level as measured by the VAS-E, the fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F (p < 0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947558", "endSection": "abstract" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1665, "text": "TRH administration was efficacious, safe, and tolerable in the treatment of CF with a positive impact on quality of life. These results provide a crucial impetus for pursuing TRH therapeutics to treat CF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Thyrotropin-releasing hormone can relieve cancer-related fatigue: hypothesis and preliminary observations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19761698", "endSection": "title" }, { "offsetInBeginSection": 657, "offsetInEndSection": 808, "text": "Global assessment using both subjective and objective parameters showed that TRH exerted clear anti-fatigue effects in four of the six TRH treatments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19761698", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1120, "text": "These initial findings support the proposal that TRH can ameliorate cancer-related fatigue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19761698", "endSection": "abstract" } ] }, { "body": "What is the role of chromomethylases in plants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22058406", "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "http://www.ncbi.nlm.nih.gov/pubmed/17660570", "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "http://www.ncbi.nlm.nih.gov/pubmed/23021223", "http://www.ncbi.nlm.nih.gov/pubmed/15282033", "http://www.ncbi.nlm.nih.gov/pubmed/9584105", "http://www.ncbi.nlm.nih.gov/pubmed/18488247", "http://www.ncbi.nlm.nih.gov/pubmed/12121623", "http://www.ncbi.nlm.nih.gov/pubmed/12151602" ], "triples": [ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3634393937006", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423147594832004", "o": "Chromomethylase" } ], "ideal_answer": [ "Chromomethylases (CMTs), which constitute a plant-specific DNA (cytosine-5)-methyltransferase family, are involved primarily in the maintenance of symmetrical CpNpG (N = A, T, C, or G) methylation and they also play a role in de novo methylation. CMTs are characterized by the presence of a chromatin-associated domain (chromodomain) inserted within the catalytic protein motifs I and IV. CMTs have likely evolved because of the high levels of CpNpG methylation present in plant genomes relative to animal genomes. The targeting of CMT methylation is accomplished by short interfering RNA (siRNA) pathways and histone methylation (H3K9, H3K27). It has been shown that transposons are in vivo targets of CMT-dependent methylation, suggesting that CMTs play a role in the plant genome surveillance. In Arabidopsis, CMTs play a key role in egg cell reprogramming and normal embryogenesis during the first few divisions of the zygote by mediating transposon and euchromatin epigenetic gene silencing. In tomatoes, CMTs are preferentially expressed in the pericarp during fruit development which suggests involvement of CMTs in the locus-specific control of methylation in the pericarp during fruit growth." ], "concepts": [ "http://www.uniprot.org/uniprot/CMT3_ARATH", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010944", "http://www.uniprot.org/uniprot/CMT2_ARATH" ], "type": "summary", "id": "51716fd38ed59a060a00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23021223", "endSection": "title" }, { "offsetInBeginSection": 88, "offsetInEndSection": 476, "text": "CHG methylation by CHROMOMETHYLASE3 (CMT3) depends on histone H3K9 dimethylation (H3K9me2), but the mechanism underlying this relationship is poorly understood. Here, we report multiple lines of evidence that CMT3 interacts with H3K9me2-containing nucleosomes. CMT3 genome locations nearly perfectly correlated with H3K9me2, and CMT3 stably associated with H3K9me2-containing nucleosomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23021223", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "A role for CHROMOMETHYLASE3 in mediating transposon and euchromatin silencing during egg cell reprogramming in Arabidopsis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "endSection": "title" }, { "offsetInBeginSection": 475, "offsetInEndSection": 1215, "text": "We also demonstrated that CHROMOMETHYLASE 3 (CMT3) is required for H3K9 dimethylation in the egg cell and for normal embryogenesis during the first few divisions of the zygote. Subsequent analysis of CMT3 mutants points to a key role in egg cell reprogramming by controlling silencing in both transposon and euchromatic regions. A speculative model of the CMT3-induced egg cell silencing is presented here, based on these results and current data from the literature suggesting the potential involvement of small RNAs targeted to the egg cell, a process conceptually similar to the division of labor described in the male gametophyte for which we show that H3K9 modifications and TFL2 localization are reminiscent of the female gametophyte.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "endSection": "sections.0" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1556, "text": "Expression analysis of eight putative tomato DNA methyltransferases encoding genes showed that one chromomethylase (CMT) and two rearranged methyltransferases (DRMs) are preferentially expressed in the pericarp during fruit growth and could be involved in the locus-specific increase of methylation observed at this developmental phase in the pericarp.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18488247", "endSection": "sections.0" }, { "offsetInBeginSection": 111, "offsetInEndSection": 346, "text": "In this study, we investigated the functional targets of the maize chromomethylase ZMET2 in multiple inbred lines to determine whether epigenetic changes conditioned by this chromomethylase are conserved or variable within the species.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17660570", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Locus-specific control of asymmetric and CpNpG methylation by the DRM and CMT3 methyltransferase genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12151602", "endSection": "title" }, { "offsetInBeginSection": 852, "offsetInEndSection": 996, "text": "However, at the SUPERMAN locus, asymmetric methylation was only completely abolished in drm1 drm2 chromomethylase 3 (cmt3) triple mutant plants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12151602", "endSection": "sections.0" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1634, "text": "The drm1 drm2 cmt3 triple mutant plants did not affect CpG methylation at any locus tested, suggesting that the primary CpG methylases are encoded by the MET1 class of genes. Although neither the drm1 drm2 double mutants nor the cmt3 single mutants show morphological defects, drm1 drm2 cmt3 triple mutant plants show pleiotropic effects on plant development. Our results suggest that the DRM and CMT3 genes act in a partially redundant and locus-specific manner to control asymmetric and CpNpG methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12151602", "endSection": "sections.0" }, { "offsetInBeginSection": 233, "offsetInEndSection": 516, "text": "Arabidopsis has two types of methyltransferases with demonstrated maintenance activity: MET1, which maintains CpG methylation and is homologous to mammalian DNMT1, and CHROMOMETHYLASE 3 (CMT3), which maintains CpNpG (N = A, T, C, or G) methylation and is unique to the plant kingdom.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12121623", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Maize chromomethylase Zea methyltransferase2 is required for CpNpG methylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "endSection": "title" }, { "offsetInBeginSection": 115, "offsetInEndSection": 298, "text": "The sequence of ZMET2 is similar to that of the Arabidopsis chromomethylases CMT1 and CMT3, with C-terminal motifs characteristic of eukaryotic and prokaryotic DNA methyltransferases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "endSection": "sections.0" }, { "offsetInBeginSection": 801, "offsetInEndSection": 902, "text": "Our research shows that chromomethylase Zmet2 is required for in vivo methylation of CpNpG sequences.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "endSection": "title" }, { "offsetInBeginSection": 310, "offsetInEndSection": 705, "text": "The cmt3 mutants displayed enhanced expression and reduced methylation of the reporter, particularly at non-CG cytosines. CNG methylation was also reduced at repetitive centromeric sequences. Thus, CMT3 is a key determinant for non-CG methylation. The lack of CMT homologs in animal genomes could account for the observation that in contrast to plants, animals maintain primarily CG methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "endSection": "sections.0" }, { "offsetInBeginSection": 262, "offsetInEndSection": 427, "text": "The 791 residue \"chromomethylase\" (CMT1) is encoded by a floral transcript that is spliced from 20 exons and is present at only approximately 1/10(-7) of total mRNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9584105", "endSection": "sections.0" } ] }, { "body": "Is curcumin a phytochemical?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25272063", "http://www.ncbi.nlm.nih.gov/pubmed/25640947", "http://www.ncbi.nlm.nih.gov/pubmed/26155681", "http://www.ncbi.nlm.nih.gov/pubmed/25543853", "http://www.ncbi.nlm.nih.gov/pubmed/25149981", "http://www.ncbi.nlm.nih.gov/pubmed/24815764", "http://www.ncbi.nlm.nih.gov/pubmed/25542083", "http://www.ncbi.nlm.nih.gov/pubmed/25964558", "http://www.ncbi.nlm.nih.gov/pubmed/24293118", "http://www.ncbi.nlm.nih.gov/pubmed/25661742", "http://www.ncbi.nlm.nih.gov/pubmed/24669820", "http://www.ncbi.nlm.nih.gov/pubmed/25541178", "http://www.ncbi.nlm.nih.gov/pubmed/24482305" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A2792113", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2792113", "o": "curcumin III" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1259941", "o": "http://linkedlifedata.com/resource/umls/label/A2792113" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2792113", "o": "C475935" }, { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Curcumin", "o": "458-37-7" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Curcumin", "o": "Curcumin" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16717035", "o": "846163" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16717035", "o": "Curcumin Oral Capsule" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2683192", "o": "http://linkedlifedata.com/resource/umls/label/A16717035" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2683192", "o": "http://linkedlifedata.com/resource/umls/label/A16717035" } ], "ideal_answer": [ "Yes, curcumin is a phytochemical derived from rhizome of turmeric Curcuma longa." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003474", "http://www.biosemantics.org/jochem#4272467", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064209" ], "type": "yesno", "id": "56b0eb3b0a360a5e45000019", "snippets": [ { "offsetInBeginSection": 366, "offsetInEndSection": 507, "text": "we analyzed turmeric from different agroclimatic regions for influence of various factors on its growth and yield of important phytochemicals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26155681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The phytochemical, curcumin, has been reported to play many beneficial roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25541178", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 470, "text": "Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent chemopreventive phytochemical that modulates various signaling pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25640947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25543853", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 261, "text": "In this study, we tested the efficacy of combining temozolomide with curcumin, a phytochemical known to inhibit glioblastoma growth, and investigated the mechanisms involved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25542083", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 583, "text": " In the present study, we investigate whether curcumin (cur), a phytochemical compound with potent anti-inflammatory effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25661742", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 126, "text": "the Phytochemicals Curcumin ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25964558", "endSection": "title" }, { "offsetInBeginSection": 327, "offsetInEndSection": 388, "text": "in combination with the phytochemicals curcumin and quercetin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25964558", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 116, "text": "Curcumin is a phytochemical derived from rhizome of turmeric Curcuma longa, present in the curry spice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25149981", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 352, "text": "Curcumin, a naturally occurring polyphenolic phytochemical isolated from the medicinal plant Curcuma longa, has anti-inflammatory activities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482305", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 400, "text": "In the present study curcumin (CUR), a known anticancer phytochemical, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24815764", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 82, "text": " Curcumin, a natural phytochemical, exhibits potent anticancer activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293118", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 355, "text": "hat curcumin, a phytochemical compound with potent anti-inflammatory properties ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669820", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 395, "text": "curcumin, a phytochemical", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25272063", "endSection": "abstract" } ] }, { "body": "What is Cerebral Cavernous Malformation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12140362", "http://www.ncbi.nlm.nih.gov/pubmed/21543988", "http://www.ncbi.nlm.nih.gov/pubmed/10235015", "http://www.ncbi.nlm.nih.gov/pubmed/26523262", "http://www.ncbi.nlm.nih.gov/pubmed/24401931", "http://www.ncbi.nlm.nih.gov/pubmed/26109568", "http://www.ncbi.nlm.nih.gov/pubmed/22711159", "http://www.ncbi.nlm.nih.gov/pubmed/8596595" ], "ideal_answer": [ "Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences", "Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences ", "Cerebral cavernous malformations (CMs) are vascular malformations of the central nervous system, causing hemorrhagic strokes, seizures, and neurological deficits." ], "type": "summary", "id": "571f2e8e0fd6f91b68000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26109568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Cerebral cavernous malformations (CMs) are vascular malformations of the central nervous system, which can be detected in the absence of any clinical symptoms. Nodules and cysts with mixed signal intensity and a peripheral hemosiderin rim are considered brain magnetic resonance imaging (MRI) findings typical of CMs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26523262", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 196, "text": "Cerebral cavernous malformations (CCM) are enlarged vascular lesions affecting 0.1-0.5% of the population worldwide and causing hemorrhagic strokes, seizures, and neurological deficits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24401931", "endSection": "abstract" }, { "offsetInBeginSection": 1887, "offsetInEndSection": 2229, "text": "Although most cerebral cavernous malformations showed evolution of hemorrhage or no change in size or shape on follow-up MR images, cerebral cavernous malformations represented as mixture of subacute and chronic hemorrhage with hemosiderin rim (type II) have a higher frequency to rebleed than other types of cerebral cavernous malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10235015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Mutations in Krev1 interaction trapped gene 1 (KRIT1) cause cerebral cavernous malformation, an autosomal dominant disease featuring malformation of cerebral capillaries resulting in cerebral hemorrhage, strokes, and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12140362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Cerebral cavernous malformation is a vascular disease of the brain causing headaches, seizures, and cerebral hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8596595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Cerebral cavernous malformation (CCM) is a common vascular disease in central nervous system that frequently predisposes to stroke, seizure, and cerebral hemorrhage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22711159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26109568", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 2078, "text": "Although most cerebral cavernous malformations showed evolution of hemorrhage or no change in size or shape on follow-up MR images, cerebral cavernous malformations represented as mixture of subacute and chronic hemorrhage with hemosiderin rim (type II) have a higher frequency to rebleed than other types of cerebral cavernous malformations. Cerebral cavernous malformations represented as hemosiderin deposition without central core (type IV) have a lower tendency to rebleed than other types and do not need any treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10235015", "endSection": "abstract" }, { "offsetInBeginSection": 1451, "offsetInEndSection": 1895, "text": "Adverse reaction of irradiation was observed in five of 22 patients treated with gamma knife surgery. Although most cerebral cavernous malformations showed evolution of hemorrhage or no change in size or shape on follow-up MR images, cerebral cavernous malformations represented as mixture of subacute and chronic hemorrhage with hemosiderin rim (type II) have a higher frequency to rebleed than other types of cerebral cavernous malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10235015", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 356, "text": "Cerebral cavernous malformations often remain clinically silent until a mutation carrier suffers a stroke or seizure. Presymptomatic genetic testing has been valuable to follow and manage cerebral cavernous malformation mutation carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21543988", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1895, "text": "Although most cerebral cavernous malformations showed evolution of hemorrhage or no change in size or shape on follow-up MR images, cerebral cavernous malformations represented as mixture of subacute and chronic hemorrhage with hemosiderin rim (type II) have a higher frequency to rebleed than other types of cerebral cavernous malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10235015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Cerebral cavernous malformation is a vascular disease of the brain causing headaches, seizures, and cerebral hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8596595", "endSection": "abstract" } ] }, { "body": "Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12955722", "http://www.ncbi.nlm.nih.gov/pubmed/9521584", "http://www.ncbi.nlm.nih.gov/pubmed/10090479", "http://www.ncbi.nlm.nih.gov/pubmed/12552564", "http://www.ncbi.nlm.nih.gov/pubmed/23146055", "http://www.ncbi.nlm.nih.gov/pubmed/20453460", "http://www.ncbi.nlm.nih.gov/pubmed/20089964", "http://www.ncbi.nlm.nih.gov/pubmed/24604962", "http://www.ncbi.nlm.nih.gov/pubmed/19367192", "http://www.ncbi.nlm.nih.gov/pubmed/19264559", "http://www.ncbi.nlm.nih.gov/pubmed/11091222", "http://www.ncbi.nlm.nih.gov/pubmed/11110674", "http://www.ncbi.nlm.nih.gov/pubmed/25002988", "http://www.ncbi.nlm.nih.gov/pubmed/10807541", "http://www.ncbi.nlm.nih.gov/pubmed/15453041", "http://www.ncbi.nlm.nih.gov/pubmed/9565158", "http://www.ncbi.nlm.nih.gov/pubmed/21438918", "http://www.ncbi.nlm.nih.gov/pubmed/12389351", "http://www.ncbi.nlm.nih.gov/pubmed/16238440", "http://www.ncbi.nlm.nih.gov/pubmed/21956823", "http://www.ncbi.nlm.nih.gov/pubmed/15657175", "http://www.ncbi.nlm.nih.gov/pubmed/12827451", "http://www.ncbi.nlm.nih.gov/pubmed/9721219", "http://www.ncbi.nlm.nih.gov/pubmed/22480464" ], "ideal_answer": [ "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified ", "Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been identified, biallelic disruption of any one of which results in this clinically defined syndrome." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "yesno", "id": "54ede5c394afd61504000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 527, "text": "Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been identified, biallelic disruption of any one of which results in this clinically defined syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21956823", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11110674", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 1146, "text": "Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11110674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10807541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified with their relative prevalence varying among the ethnical backgrounds", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10090479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 497, "text": "Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12389351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10807541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10090479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Among patients with bone marrow failure (BMF) syndrome, some are happened to have underlying Fanconi anemia (FA), a genetically heterogeneous disease, which is characterized by progressive pancytopenia and cancer susceptibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20453460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Fanconi anemia is a genetically heterogeneous recessive disease characterized mainly by bone marrow failure and cancer predisposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16238440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "INTRODUCTION: Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20089964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25002988", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 661, "text": "Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21438918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Fanconi anemia (FA) is a genetically heterogeneous disease with at least eight genes on the basis of complementation groups (FAA to FAH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9721219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11110674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A-H).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11091222", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 253, "text": "FA is a genetically heterogeneous disease with at least seven genes so far identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12955722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Fanconi anemia (FA) is an autosomal recessive rare disease characterized by progressive pancytopenia, congenital malformations and predisposition to acute myeloid leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15453041", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 281, "text": "Fanconi anemia is genetically heterogeneous, with at least eight complementation groups of FA (FAA to FAD2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15453041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10090479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10807541", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 289, "text": "The disease is clinically heterogeneous; eight different complementation groups (FA A-H) and, thus, genetic loci have been discovered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9521584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The hereditary genetic disorder Fanconi anemia (FA) belongs to the heterogeneous group of diseases associated with defective DNA damage repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19264559", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 441, "text": "The clinical manifestations of FA are heterogeneous, but one common outcome in the majority of patients is the development of life-threatening hematologic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9565158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Fanconi anemia is a genetically heterogeneous chromosomal breakage disorder exhibiting a high degree of clinical variability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19367192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15657175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive syndrome associated with chromosomal instability, hypersensitivity to DNA cross-linking agents, and predisposition to malignancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12552564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Fanconi anemia (FA) is a rare autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12827451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24604962", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 660, "text": "Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21438918", "endSection": "abstract" } ] }, { "body": "Which protein pathway is regulating SGK1-mediated phosphorylation of FOXO3a to control cell proliferation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24558442" ], "ideal_answer": [ "mTORC1, in coordination with mTORC2, controls cell proliferation by regulating FoxO3a gene expression and SGK1-mediated phosphorylation of FOXO3a at Ser314." ], "exact_answer": [ "The mTOR pathway" ], "type": "factoid", "id": "56cafa845795f9a73e00002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The mTOR pathway controls cell proliferation by regulating the FoxO3a transcription factor via SGK1 kinase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558442", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 427, "text": "the FoxO3a transcription factor is coordinately regulated by mTORC1 and mTORC2, and plays a crucial role in controlling cell proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558442", "endSection": "abstract" }, { "offsetInBeginSection": 1370, "offsetInEndSection": 1525, "text": "mTORC1, in coordination with mTORC2, controls cell proliferation by regulating FoxO3a gene expression and SGK1-mediated phosphorylation of FoxO3a at Ser314", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558442", "endSection": "abstract" }, { "offsetInBeginSection": 1343, "offsetInEndSection": 1525, "text": "These results suggest that mTORC1, in coordination with mTORC2, controls cell proliferation by regulating FoxO3a gene expression and SGK1-mediated phosphorylation of FoxO3a at Ser314", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558442", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1527, "text": "SGK1 overexpression suppressed CDKI expression in p18-deficient cells, whereas SGK1 knockdown induced CDKI expression in wild-type cells, resulting in the suppression of cell proliferation. These results suggest that mTORC1, in coordination with mTORC2, controls cell proliferation by regulating FoxO3a gene expression and SGK1-mediated phosphorylation of FoxO3a at Ser314.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24558442", "endSection": "abstract" } ] }, { "body": "Which drugs have been found effective for the treatment of chordoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21905773", "http://www.ncbi.nlm.nih.gov/pubmed/21801998", "http://www.ncbi.nlm.nih.gov/pubmed/19723879", "http://www.ncbi.nlm.nih.gov/pubmed/20965848", "http://www.ncbi.nlm.nih.gov/pubmed/23792643" ], "ideal_answer": [ "Established chordoma cell lines, and patient-derived primary cell cultures, as well as chordoma tumors in vivo were found to be sensitive to treatment with bortezomib, vincristine, doxorubicin, etoposide, cisplatin, fludarabine and SD-1029 Stat3 inhibitor. Moreover, percutaneous intratumoral injection with pingyangmycin lipiodol emulsion was shown to be effective against chordoma. It should be stressed that combination treatment with the use of the above drugs was always able to increase the therapeutic potency." ], "exact_answer": [ [ "bortezomib" ], [ "vincristine" ], [ "doxorubicin" ], [ "etoposide" ], [ "cisplatin" ], [ "fludarabine" ], [ "SD-1029 Stat3 inhibitor" ], [ "pingyangmycin lipiodol emulsion" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.disease-ontology.org/api/metadata/DOID:3302", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002817", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035690", "http://www.disease-ontology.org/api/metadata/DOID:4153", "http://www.disease-ontology.org/api/metadata/DOID:4151" ], "type": "list", "id": "532b15ecd6d3ac6a34000014", "snippets": [ { "offsetInBeginSection": 1436, "offsetInEndSection": 1595, "text": "The combination treatment of bortezomib with topoisomerase I and II inhibitors increased the therapeutic potency in U-CH2 and patient-derived primary cultures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23792643", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1581, "text": "Vincristine, doxorubicin, etoposide, cisplatin, and fludarabine, each at a concentration of 10 \u03bcM, decreased the number of chordoma cells when given alone down to 11%, 0%, 30%, 67%, and 3%, respectively. Etoposide and cisplatin, each at a concentration of 10 \u03bcM, reduced the percentage of viable chordoma cells in a more effective way when given with 1 \u03bcM ATRA simultaneously, reducing the number of viable cells to 14% and 9%, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21905773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Percutaneous intratumoral injection with pingyangmycin lipiodol emulsion for the treatment of recurrent sacrococcygeal chordomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21801998", "endSection": "title" }, { "offsetInBeginSection": 581, "offsetInEndSection": 749, "text": "Preliminary results showed that PIIT with pingyangmycin lipiodol emulsion under fluoroscopic guidance is effective and safe and may be considered as a treatment option.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21801998", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 125, "text": "Percutaneous intratumoral injection with pingyangmycin lipiodol emulsion for treatment of recurrent sacrococcygeal chordomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20965848", "endSection": "title" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1266, "text": "During the follow-up (median time of 21.7 months, range 10-26 months), all the patients showed obviously reduced tumor size and VAS, and partial remission was achieved in 6 patients and stable disease (SD) in 1 patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20965848", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1511, "text": "Fluoroscopy-guided percutaneous intratumoral injection of PLE can be effective and safe and may serve as a alternative for treatment of recurrent sacrococcygeal chordomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20965848", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1205, "text": "The expression of Stat3 signaling cascade was inhibited in all chordoma cell lines after treatment with SD-1029. The cytotoxicity of the combination of SD-1029 and chemotherapeutic drugs is significantly better than either agent alone. Phosphorylation of Stat3 in chordoma cells in vitro and cellular proliferation in three-dimensional culture were inhibited by SD-1029.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19723879", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1431, "text": "In conclusion, the Stat3 pathway is constitutively activated in chordomas and the level of expression may serve as a predictor for prognosis. Blockade of the Stat3 pathway represents a potential strategy for future treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19723879", "endSection": "abstract" } ] }, { "body": "Which components of the stress granules are known to be related to motor neuron degeneration in Amyotrophic Lateral Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23474818", "http://www.ncbi.nlm.nih.gov/pubmed/25216585", "http://www.ncbi.nlm.nih.gov/pubmed/19338576", "http://www.ncbi.nlm.nih.gov/pubmed/20699327", "http://www.ncbi.nlm.nih.gov/pubmed/25429138", "http://www.ncbi.nlm.nih.gov/pubmed/19815002", "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "http://www.ncbi.nlm.nih.gov/pubmed/26557057", "http://www.ncbi.nlm.nih.gov/pubmed/21280085", "http://www.ncbi.nlm.nih.gov/pubmed/24804206", "http://www.ncbi.nlm.nih.gov/pubmed/22879928", "http://www.ncbi.nlm.nih.gov/pubmed/19765185" ], "ideal_answer": [ "Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS.", "TDP-43 and FUS have been identified as key proteins in the pathogenesis of some cases of ALS. Although their role in motor neuron degeneration is not yet known, TDP-43 and FUS have been shown to accumulate in RNA stress granules (SGs) in cell models and in spinal cord tissue from Amyotrophic Lateral Sclerosis (ALS) patients." ], "exact_answer": [ [ "TDP-43" ], [ "FUS" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012598", "http://www.disease-ontology.org/api/metadata/DOID:230", "http://www.disease-ontology.org/api/metadata/DOID:332", "http://amigo.geneontology.org/amigo/term/GO:0034063", "http://amigo.geneontology.org/amigo/term/GO:0035617", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000690" ], "type": "list", "id": "56c830635795f9a73e00000e", "snippets": [ { "offsetInBeginSection": 460, "offsetInEndSection": 877, "text": "Here, we demonstrate that C-terminal ALS mutations disrupt the nuclear localizing signal (NLS) of FUS resulting in cytoplasmic accumulation in transfected cells and patient fibroblasts. FUS mislocalization is rescued by the addition of the wild-type FUS NLS to mutant proteins. We also show that oxidative stress recruits mutant FUS to cytoplasmic stress granules where it is able to bind and sequester wild-type FUS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474818", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 425, "text": "Recently, TDP-43 has been identified as a key protein in the pathogenesis of some cases of ALS. Although the role of TDP-43 in motor neuron degeneration is not yet known, TDP-43 has been shown to accumulate in RNA stress granules (SGs) in cell models and in spinal cord tissue from ALS patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22879928", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 1079, "text": "in response to oxidative stress or heat shock conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type FUS, assembled into perinuclear stress granules in proportion to their cytoplasmic expression levels. These findings demonstrate a potential link between FUS mutations and cellular pathways involved in stress responses that may be relevant to altered motor neuron homeostasis in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20699327", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1306, "text": "both stress granules (TIA-1 immunoreactive) and processing bodies (P-bodies; XRN-1 immunoreactive) were more prevalent in ALS motor neurons than in controls and demonstrated strong co-localization with TDP-43.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19815002", "endSection": "abstract" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1664, "text": "These data suggest that NFL mRNA processing is fundamentally altered in ALS spinal motor neurons to favour compartmentalization within both stress granules and P-bodies, and that TDP-43 plays a fundamental role in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19815002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 605, "text": "Transactive response DNA-binding protein 43 (TDP-43) forms abnormal ubiquitinated and phosphorylated inclusions in brain tissues from patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. TDP-43 is a DNA/RNA-binding protein involved in RNA processing, such as transcription, pre-mRNA splicing, mRNA stabilization and transport to dendrites. We found that in response to oxidative stress and to environmental insults of different types TDP-43 is capable to assemble into stress granules (SGs), ribonucleoprotein complexes where protein synthesis is temporarily arrested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19765185", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 902, "text": "Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26557057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Mutations in fused in sarcoma (FUS), a DNA/RNA binding protein, have been associated with familial amyotrophic lateral sclerosis (fALS), which is a fatal neurodegenerative disease that causes progressive muscular weakness and has overlapping clinical and pathologic characteristics with frontotemporal lobar degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216585", "endSection": "abstract" }, { "offsetInBeginSection": 1634, "offsetInEndSection": 1843, "text": "Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090136", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 861, "text": "Expression of ALS-linked FUS mutations resulted in their assembly into cytoplasmic stress granules (SGs), cellular structures that package mRNA and RNA-binding proteins during cell stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21280085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "TDP-43 is an RNA-binding protein linked to amyotrophic lateral sclerosis (ALS) that is known to regulate the splicing, transport, and storage of specific mRNAs into stress granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25429138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder consisting of progressive loss of motor neurons. TDP-43 has been identified as a component of ubiquitin-immunoreactive inclusions of motor neurons in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19338576", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 543, "text": "SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26557057", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1233, "text": "PTE significantly reduced the incorporation of R521C FUS/TLS into stress granules under stress conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24804206", "endSection": "abstract" } ] }, { "body": "Is there evidence for de novo genesis of enhancers in vertebrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22069375" ], "ideal_answer": [ "Yes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014714" ], "type": "yesno", "id": "56ae71cb0a360a5e45000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "De novo genesis of enhancers in vertebrates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1096, "text": "Evolutionary innovation relies partially on changes in gene regulation. While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. We found that these regions show enhancer activity while the orthologous coding regions have no regulatory activity. These results demonstrate that these enhancers have been de novo generated in fish. By revealing that minor changes in non-regulatory sequences are sufficient to generate new enhancers, our study highlights an important playground for creating new regulatory variability and evolutionary innovation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 523, "text": "Here we show evidence for the de novo genesis of enhancers in vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 679, "text": "While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 375, "text": "While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 680, "text": "While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 452, "text": "Here we show evidence for the de novo genesis of enhancers in vertebrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 452, "text": "While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069375", "endSection": "abstract" } ] }, { "body": "Which could be some of the possible causes of hypersomnia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12486284", "http://www.ncbi.nlm.nih.gov/pubmed/8491310", "http://www.ncbi.nlm.nih.gov/pubmed/9381026", "http://www.ncbi.nlm.nih.gov/pubmed/11022396", "http://www.ncbi.nlm.nih.gov/pubmed/17584779", "http://www.ncbi.nlm.nih.gov/pubmed/10953647", "http://www.ncbi.nlm.nih.gov/pubmed/14638887", "http://www.ncbi.nlm.nih.gov/pubmed/16416710", "http://www.ncbi.nlm.nih.gov/pubmed/25080137" ], "ideal_answer": [ "Sleep-wake disturbances (SWD) with hypersomnia are common after traumatic brain injury (TBI), with decreased CSF levels of hypocretin-1, a wake-promoting neurotransmitter, in cases of sleep apnea, as well as in up to half the patients with dementia, particularly in vascular dementia, Korsakow syndrome, Parkinson's disease, and depression, where the alteration of sleep architecture may be pronounced, whereas in Alzheimer's disease prominent hypersomnolence or insomnia is typically only found in later stages of the diseases." ], "exact_answer": [ [ "traumatic brain injury (TBI)" ], [ "sleep apnea" ], [ "dementia" ] ], "type": "list", "id": "5720a8da0fd6f91b68000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Sleep-wake disturbances (SWD) are common after traumatic brain injury (TBI). In acute TBI, we recently found decreased CSF levels of hypocretin-1, a wake-promoting neurotransmitter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584779", "endSection": "abstract" }, { "offsetInBeginSection": 1833, "offsetInEndSection": 1930, "text": "Hypocretin levels 6 months after TBI were significantly lower in patients with post-traumatic EDS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584779", "endSection": "abstract" }, { "offsetInBeginSection": 2178, "offsetInEndSection": 2334, "text": "These results suggest that sleep-wake disturbances, particularly EDS, fatigue and hypersomnia are common after TBI, and significantly impair quality of life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "When sleepiness is excessive, undesirable, inappropriate or unexplained, it often indicates a clinical disorder that is generically termed hypersomnia. One of the leading causes of hypersomnia is sleep apnea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11022396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 583, "text": "A clinically relevant sleep-wake disturbance is found in up to half the patients with dementia, and the sundowning agitation is a common cause of institutionalisation of demented geriatric patients. The circadian rhythm of demented patients is levelled off with increased daytime sleep and disrupted night sleep. Particularly in vascular dementia, Korsakow syndrome, Parkinson's disease, and depression the alteration of sleep architecture may be pronounced, whereas in Alzheimer's disease prominent hypersomnolence or insomnia is typically only found in later stages of the diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9381026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "We report on an 83 yr old man with hypersomnia and central sleep apnoea (CSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8491310", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 263, "text": "One of the leading causes of hypersomnia is sleep apnea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11022396", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1913, "text": "In this article, the causes of hypersomnia are detailed following the conventional classification of hypersomnic syndromes: narcolepsy, idiopathic hypersomnia, recurrent hypersomnia, insufficient sleep syndrome, medication- and toxin-dependent sleepiness, hypersomnia associated with psychiatric disorders, hypersomnia associated with neurological disorders, posttraumatic hypersomnia, infection (with a special emphasis on the differences between bacterial and viral diseases compared with parasitic diseases, such as sleeping sickness) and hypersomnia, hypersomnia associated with metabolic or endocrine diseases, breathing-related sleep disorders and sleep apnea syndromes, and periodic limb movements in sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16416710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "In the absence of sleep deprivation (either because of behavioral or medical causes) or pharmacologically induced sleepiness, hypersomnia is a manifestation of one of the central disorders of hypersomnolence, such as narcolepsy types 1 and 2, idiopathic hypersomnia, and recurrent hypersomnias such as Kleine-Levin syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25080137", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 885, "text": "Sleep apnea syndrome (SAS), narcolepsy, chronic sleep deprivation (insufficiency), and restless legs/periodic limb movements in sleep syndrome (RLS/PLMS) represent the most common causes of hypersomnia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10953647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12486284", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 209, "text": "One of the leading causes of hypersomnia is sleep apnea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11022396", "endSection": "abstract" } ] }, { "body": "What is the function of caspases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12407171", "http://www.ncbi.nlm.nih.gov/pubmed/18483489", "http://www.ncbi.nlm.nih.gov/pubmed/16103108", "http://www.ncbi.nlm.nih.gov/pubmed/9874792", "http://www.ncbi.nlm.nih.gov/pubmed/22541691", "http://www.ncbi.nlm.nih.gov/pubmed/12170777", "http://www.ncbi.nlm.nih.gov/pubmed/11679590", "http://www.ncbi.nlm.nih.gov/pubmed/17091579", "http://www.ncbi.nlm.nih.gov/pubmed/12934068", "http://www.ncbi.nlm.nih.gov/pubmed/18544666", "http://www.ncbi.nlm.nih.gov/pubmed/11551979", "http://www.ncbi.nlm.nih.gov/pubmed/10888847", "http://www.ncbi.nlm.nih.gov/pubmed/15970694", "http://www.ncbi.nlm.nih.gov/pubmed/12933355", "http://www.ncbi.nlm.nih.gov/pubmed/23139158", "http://www.ncbi.nlm.nih.gov/pubmed/15723613", "http://www.ncbi.nlm.nih.gov/pubmed/11553704", "http://www.ncbi.nlm.nih.gov/pubmed/11489831", "http://www.ncbi.nlm.nih.gov/pubmed/18955972", "http://www.ncbi.nlm.nih.gov/pubmed/14555221", "http://www.ncbi.nlm.nih.gov/pubmed/10511707", "http://www.ncbi.nlm.nih.gov/pubmed/11032171", "http://www.ncbi.nlm.nih.gov/pubmed/16284213", "http://www.ncbi.nlm.nih.gov/pubmed/15711100", "http://www.ncbi.nlm.nih.gov/pubmed/21238939", "http://www.ncbi.nlm.nih.gov/pubmed/15967022", "http://www.ncbi.nlm.nih.gov/pubmed/11996667", "http://www.ncbi.nlm.nih.gov/pubmed/10794589", "http://www.ncbi.nlm.nih.gov/pubmed/14646471", "http://www.ncbi.nlm.nih.gov/pubmed/10739653", "http://www.ncbi.nlm.nih.gov/pubmed/18729734", "http://www.ncbi.nlm.nih.gov/pubmed/17181147", "http://www.ncbi.nlm.nih.gov/pubmed/15450935", "http://www.ncbi.nlm.nih.gov/pubmed/22633487", "http://www.ncbi.nlm.nih.gov/pubmed/20846841", "http://www.ncbi.nlm.nih.gov/pubmed/17013363", "http://www.ncbi.nlm.nih.gov/pubmed/16622074", "http://www.ncbi.nlm.nih.gov/pubmed/16700650", "http://www.ncbi.nlm.nih.gov/pubmed/11573949", "http://www.ncbi.nlm.nih.gov/pubmed/19473994", "http://www.ncbi.nlm.nih.gov/pubmed/17082813" ], "ideal_answer": [ "Caspases are intracellular proteases that propagate programmed cell death, proliferation, and inflammation." ], "exact_answer": [ "Caspases are intracellular proteases that propagate programmed cell death, proliferation, and inflammation." ], "concepts": [ "http://www.uniprot.org/uniprot/ICE_DROME", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020169", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004197", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053143", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097202", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020170" ], "type": "factoid", "id": "54f5bc7d5f206a0c06000001", "snippets": [ { "offsetInBeginSection": 81, "offsetInEndSection": 164, "text": "Caspases are the ultimate executors of the apoptotic programmed cell death pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23139158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Members of the caspase family of cysteine proteases coordinate the morphological and biochemical events that typify apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Caspase function is known to be essential for cell death by apoptosis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Caspases, initially identified as a family of proteases regulating cell death, have been found to have nonapoptotic functions as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21238939", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 186, "text": ". As in other organisms, apoptosis is executed by caspases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20846841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Caspases are intracellular proteases that propagate programmed cell death, proliferation, and inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19473994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Apoptosis is dependent upon caspase activation leading to substrate cleavage and, ultimately, cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18955972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Caspases are a family of evolutionarily conserved cysteine proteases that constitute the effector arm of the apoptotic machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10794589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Caspases are critical mediators of apoptosis, the principle mechanism by which extra and harmful cells are eliminated to ensure proper development and maintain cellular homeostasis in all multicellular organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10739653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Caspases (cysteine-containing aspartate-specific proteases) are at the core of the cell's suicide machinery. These enzymes, once activated, dismantle the cell by selectively cleaving key proteins after aspartate residues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10888847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Programmed cell death plays an important role in maintaining homeostasis during animal development, and has been conserved in animals as different as nematodes and humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11032171", "endSection": "abstract" } ] }, { "body": "Is TNNI3K a cardiac-specific protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18552163", "http://www.ncbi.nlm.nih.gov/pubmed/23085512", "http://www.ncbi.nlm.nih.gov/pubmed/24132636", "http://www.ncbi.nlm.nih.gov/pubmed/20018082", "http://www.ncbi.nlm.nih.gov/pubmed/19925440", "http://www.ncbi.nlm.nih.gov/pubmed/12721663", "http://www.ncbi.nlm.nih.gov/pubmed/21314842", "http://www.ncbi.nlm.nih.gov/pubmed/23369981", "http://www.ncbi.nlm.nih.gov/pubmed/17660584", "http://www.ncbi.nlm.nih.gov/pubmed/23472207", "http://www.ncbi.nlm.nih.gov/pubmed/18021318" ], "ideal_answer": [ "Yes, TNNI3K is highly expressed in heart but is undetectable in other tissues." ], "exact_answer": "yes", "type": "yesno", "id": "551c4ffc6b348bb82c000010", "snippets": [ { "offsetInBeginSection": 18, "offsetInEndSection": 55, "text": "cardiomyocyte-specific kinase TNNI3K ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24132636", "endSection": "title" }, { "offsetInBeginSection": 382, "offsetInEndSection": 477, "text": "We report that cardiac troponin I-interacting kinase (TNNI3K), a cardiomyocyte-specific kinase,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24132636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 35, "text": "TNNI3K, a cardiac-specific kinase, ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472207", "endSection": "title" }, { "offsetInBeginSection": 106, "offsetInEndSection": 236, "text": " The cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac specific kinase, is associated with cardiomyocyte hypertrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472207", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 286, "text": "Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23369981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunctio", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085512", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase whose biological function remains largely unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085512", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 89, "text": " Cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific kinase gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21314842", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 873, "text": " a novel cardiac-specific kinase gene (TNNI3K),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20018082", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 547, "text": " TNNI3K is a novel cardiac troponin I-interacting kinase gene and its overexpression may promote cardiac myogenesis, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19925440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "TNNI3K is a new cardiac-specific MAP kinase whose gene is localized to 1p31.1 and that belongs to a tyrosine kinase-like branch in the kinase tree of the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18552163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The cardiac ankyrin repeat kinase (CARK) gene, also named TNNI3K for its interaction with cardiac troponin I, is both a unique expression and heart-enriched gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18021318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Molecular cloning of cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac-specific protein kinase containing seven N-terminal ankyrin (ANK) repeats followed by a protein kinase domain and a C-terminal Ser-rich domain, has previously been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17660584", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 546, "text": " TNNI3K is highly expressed in heart, but is undetectable in other tissues. Immunohistochemical analysis predominantly localized TNNI3K in the nucleus of cardiac myocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12721663", "endSection": "abstract" } ] }, { "body": "How does Rif1 regulate DNA replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24462468", "http://www.ncbi.nlm.nih.gov/pubmed/24656819", "http://www.ncbi.nlm.nih.gov/pubmed/23809990", "http://www.ncbi.nlm.nih.gov/pubmed/24685139", "http://www.ncbi.nlm.nih.gov/pubmed/22850673", "http://www.ncbi.nlm.nih.gov/pubmed/24634216", "http://www.ncbi.nlm.nih.gov/pubmed/24879017", "http://www.ncbi.nlm.nih.gov/pubmed/24532715", "http://www.ncbi.nlm.nih.gov/pubmed/22279046", "http://www.ncbi.nlm.nih.gov/pubmed/19948482", "http://www.ncbi.nlm.nih.gov/pubmed/22850674", "http://www.ncbi.nlm.nih.gov/pubmed/15342490" ], "ideal_answer": [ "Rif1 (Rap1-interacting-factor-1), originally identified as a telomere-binding factor in yeast, is a critical determinant of the replication timing programme in human cells. Rif1 tightly binds to nuclear-insoluble structures at late-M-to-early-G1 and regulates chromatin-loop sizes. Furthermore, Rif1 colocalizes specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S replication domains that are restrained from being activated at early-S-phase. Overall, Rif1 plays crucial roles in determining the replication timing domain structures in human cells through regulating higher-order chromatin architecture. This function of Rif1 depends on its interaction with PP1 phosphatases and the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK." ], "type": "summary", "id": "5710ed19a5ed216440000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Protein phosphatase 1 recruitment by Rif1 regulates DNA replication origin firing by counteracting DDK activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24656819", "endSection": "title" }, { "offsetInBeginSection": 110, "offsetInEndSection": 401, "text": "Yeast Rif1 associates with telomeres and regulates their length. In contrast, human Rif1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in ALT cells, a pattern of telomere association typical of DNA-damage-response factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342490", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 523, "text": "After induction of double-strand breaks (DSBs), Rif1 formed foci that colocalized with other DNA-damage-response factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342490", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1168, "text": "These data reveal that human Rif1 contributes to the ATM-mediated protection against DNA damage and point to a remarkable difference in the primary function of this protein in yeast and mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15342490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Mammalian Rif1 contributes to replication stress survival and homology-directed repair.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948482", "endSection": "title" }, { "offsetInBeginSection": 359, "offsetInEndSection": 563, "text": "Rif1 deficiency leads to failure in embryonic development, and conditional deletion of Rif1 from mouse embryo fibroblasts affects S-phase progression, rendering cells hypersensitive to replication poisons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948482", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 688, "text": "Rif1 deficiency does not alter the activation of the DNA replication checkpoint but rather affects the execution of repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948482", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1112, "text": "Consistent with a role in S-phase progression, Rif1 accumulates at stalled replication forks, preferentially around pericentromeric heterochromatin. Collectively, these findings reveal a function for Rif1 in the repair of stalled forks by facilitating HDR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Rif1 regulates the replication timing domains on the human genome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850674", "endSection": "title" }, { "offsetInBeginSection": 277, "offsetInEndSection": 449, "text": " Rif1 (Rap1-interacting-factor-1), originally identified as a telomere-binding factor in yeast, is a critical determinant of the replication timing programme in human cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850674", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 642, "text": "Depletion of Rif1 results in specific loss of mid-S replication foci profiles, stimulation of initiation events in early-S-phase and changes in long-range replication timing domain structures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850674", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 987, "text": "Rif1 tightly binds to nuclear-insoluble structures at late-M-to-early-G1 and regulates chromatin-loop sizes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850674", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1353, "text": "Rif1 colocalizes specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S replication domains that are restrained from being activated at early-S-phase. Our results indicate that Rif1 plays crucial roles in determining the replication timing domain structures in human cells through regulating higher-order chromatin architecture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850674", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 261, "text": "mouse Rif1 as a key player in the regulation of DNA replication timin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850673", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850673", "endSection": "title" }, { "offsetInBeginSection": 277, "offsetInEndSection": 392, "text": "Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850673", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 623, "text": "Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850673", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 744, "text": "Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850673", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Rif1 is a global regulator of timing of replication origin firing in fission yeast", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22279046", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 436, "text": "We identified rif1\u0394, a null mutant of rif1(+), a conserved telomere-binding factor, as an efficient bypass mutant of fission yeast hsk1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22279046", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 687, "text": "At the same time, many early-firing, efficient origins are suppressed or delayed in firing timing in rif1\u0394", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22279046", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 945, "text": "Rif1 binds not only to telomeres, but also to many specific locations on the arm segments that only partially overlap with the prereplicative complex assembly sites, although Rif1 tends to bind in the vicinity of the late/dormant origins activated in rif1\u0394", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22279046", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1256, "text": "Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22279046", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 103, "text": "Rif1 as a global regulator of replication timing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23809990", "endSection": "title" }, { "offsetInBeginSection": 433, "offsetInEndSection": 556, "text": "Rif1 which plays crucial roles in the regulation of the replication timing program in yeast as well as in higher eukaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23809990", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 849, "text": "In mammalian cells, Rif1 appears to regulate the structures of replication timing domains through its ability to organize chromatin loop structures. Regulation of chromatin architecture by Rif1 may be linked to other chromosome transactions including recombination, repair, or transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23809990", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 590, "text": "Rif1 has recently been identified as a genome-wide regulator of replication timing in fission yeast and in mammalian cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24879017", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 807, "text": "However, previous studies in budding yeast have suggested that Rif1's role in controlling replication timing may be limited to subtelomeric domains and derives from its established role in telomere length regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24879017", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 1003, "text": "We have analyzed replication timing by analyzing BrdU incorporation genome-wide, and report that Rif1 regulates the timing of late/dormant replication origins throughout the S. cerevisiae genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24879017", "endSection": "abstract" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1482, "text": "Rif1 regulates replication timing through a mechanism independent of this checkpoint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24879017", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1874, "text": "the Rif1 mechanism regulates origin timing irrespective of proximity to a chromosome end, and suggest instead that telomere sequences merely provide abundant binding sites for proteins that recruit Rif1. Still, the abundance of Rif1 binding in telomeric domains may facilitate Rif1-mediated repression of non-telomeric origins that are more distal from centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24879017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24532715", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 473, "text": "Mammalian Rif1 is a key regulator of DNA replication timing, double-stranded DNA break repair, and replication fork restart. Dissecting the molecular functions of Rif1 is essential to understand how it regulates such diverse processes. However, Rif1 is a large protein that lacks well defined functional domains and is predicted to be largely intrinsically disordered; these features have hampered recombinant expression of Rif1 and subsequent functional characterization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24634216", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1371, "text": "the first structural study of the mammalian Rif1, identifying a domain that directly links its function to DNA binding. The high specificity of Rif1 for cruciform structures is significant given the role of this key protein in regulating origin firing and DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24634216", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "RIF1: a novel regulatory factor for DNA replication and DNA damage response signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24462468", "endSection": "title" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1216, "text": "Rif1 is conserved from yeast to humans but its function has evolved from telomere length regulation in yeast to the maintenance of genome integrity in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24462468", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1390, "text": "Recently its role in the maintenance of genomic integrity has been expanded to include the regulation of chromatin structure, replication timing and intra-S phase checkpoint", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24462468", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 264, "text": "budding yeast Rif1 protein inhibits activation of prereplication complexes (pre-RCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685139", "endSection": "title" }, { "offsetInBeginSection": 630, "offsetInEndSection": 1068, "text": "Rif1 also interacts with Dbf4 in yeast two-hybrid assays, further implicating this protein in direct modulation of pre-RC activation through the DDK. Finally, we demonstrate Rif1 RVxF/SILK motif-dependent recruitment of Glc7 to telomeres and earlier replication of these regions in cells where the motifs are mutated. Our data thus link Rif1 to negative regulation of replication origin firing through recruitment of the Glc7 phosphatase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685139", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 427, "text": "Rif1, originally identified as a telomeric protein, was recently implicated in specifying replication timing in yeast and mammals. We show that this function of Rif1 depends on its interaction with PP1 phosphatases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24656819", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 977, "text": "Our data suggest that the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK. These findings elucidate the mechanism of action of Rif1 in the control of DNA replication and demonstrate a role of PP1 phosphatases in the regulation of origin firing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24656819", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 707, "text": "Recent studies have identified factors that regulate the timing of origin activation, including Rif1 which plays crucial roles in the regulation of the replication timing program in yeast as well as in higher eukaryotes. In mammalian cells, Rif1 appears to regulate the structures of replication timing domains through its ability to organize chromatin loop structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23809990", "endSection": "abstract" } ] }, { "body": "Is factor XI deficient in Hemophilia C?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18378181", "http://www.ncbi.nlm.nih.gov/pubmed/18160615", "http://www.ncbi.nlm.nih.gov/pubmed/20485963", "http://www.ncbi.nlm.nih.gov/pubmed/1546275", "http://www.ncbi.nlm.nih.gov/pubmed/8277060" ], "ideal_answer": [ "Factor XI deficiency is associated with a bleeding tendency called Hemophilia C." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006467", "http://www.disease-ontology.org/api/metadata/DOID:2229", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005173", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005172" ], "type": "yesno", "id": "51588c1ad24251bc05000094", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 152, "text": "Factor XI deficiency is a rare hematologic disorder. Hemophilia C (factor XI deficiency) affects both genders and it is usually asymptomatic,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20485963", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Congenital factor XI deficiency (also known as the Rosenthal syndrome or hemophilia C)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18378181", "endSection": "sections.0" }, { "offsetInBeginSection": 21, "offsetInEndSection": 290, "text": "rare case of an acute cerebral aneurysm rupture in a patient with a known factor XI deficiency. Aneurysmal subarachnoid hemorrhage (SAH) accounts for a high mortality and morbidity rate. When SAH is associated with an inherited coagulation disorder such as hemophilia C", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18160615", "endSection": "sections.0" }, { "offsetInBeginSection": 127, "offsetInEndSection": 162, "text": "Factor XI deficiency (Hemophilia C)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8277060", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Factor XI deficiency, also called hemophilia C,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1546275", "endSection": "sections.0" } ] }, { "body": "What is known about food intolerance and gluten ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23567359", "http://www.ncbi.nlm.nih.gov/pubmed/23496382", "http://www.ncbi.nlm.nih.gov/pubmed/16313685", "http://www.ncbi.nlm.nih.gov/pubmed/17979710", "http://www.ncbi.nlm.nih.gov/pubmed/23767452", "http://www.ncbi.nlm.nih.gov/pubmed/20036949" ], "ideal_answer": [ "Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals.\nEmerging research into a syndrome known as nonceliac gluten sensitivity suggests a heterogeneous condition with some features of celiac disease but often categorized as FGIDs, including IBS.", "Coeliac disease is a multifactorial disease characterized by a dysregulated immune response to ingested wheat gluten and related cereal proteins. With an incidence of about 1% of the general population, it is considered the most common food intolerance disorder.Emerging research into a syndrome known as nonceliac gluten sensitivity suggests a heterogeneous condition with some features of celiac disease but often categorized as FGIDs, including IBS." ], "type": "summary", "id": "550300fce9bde6963400000a", "snippets": [ { "offsetInBeginSection": 851, "offsetInEndSection": 917, "text": "At present, there is no specific bio-marker of gluten sensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23767452", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1311, "text": "Emerging research into a syndrome known as nonceliac gluten sensitivity suggests a heterogeneous condition with some features of celiac disease but often categorized as FGIDs, including IBS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23496382", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 472, "text": "Gluten intolerance is a unique model of autoimmune disease in which we can recognize the main environmental factor (gluten) and the more complex genetic background.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20036949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Coeliac disease is a multifactorial disease characterized by a dysregulated immune response to ingested wheat gluten and related cereal proteins. With an incidence of about 1% of the general population, it is considered the most common food intolerance disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17979710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Coeliac disease is a lifelong intolerance to the gluten found in wheat, barley and rye, and some patients are also sensitive to oats. The disease is genetically determined, with 10% of the first-degree relatives affected and 75% of monozygotic twins being concordant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16313685", "endSection": "abstract" } ] }, { "body": "Are EDNRB mutations involved in the development of Hirschsprung disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15834508", "http://www.ncbi.nlm.nih.gov/pubmed/12631670", "http://www.ncbi.nlm.nih.gov/pubmed/14633923", "http://www.ncbi.nlm.nih.gov/pubmed/11471546", "http://www.ncbi.nlm.nih.gov/pubmed/15294878", "http://www.ncbi.nlm.nih.gov/pubmed/12574515", "http://www.ncbi.nlm.nih.gov/pubmed/20009762", "http://www.ncbi.nlm.nih.gov/pubmed/16145050", "http://www.ncbi.nlm.nih.gov/pubmed/20633936", "http://www.ncbi.nlm.nih.gov/pubmed/9035203", "http://www.ncbi.nlm.nih.gov/pubmed/11434563", "http://www.ncbi.nlm.nih.gov/pubmed/12355085", "http://www.ncbi.nlm.nih.gov/pubmed/9094028", "http://www.ncbi.nlm.nih.gov/pubmed/18693272", "http://www.ncbi.nlm.nih.gov/pubmed/11484199", "http://www.ncbi.nlm.nih.gov/pubmed/16618617", "http://www.ncbi.nlm.nih.gov/pubmed/10664228", "http://www.ncbi.nlm.nih.gov/pubmed/10792313", "http://www.ncbi.nlm.nih.gov/pubmed/14669347", "http://www.ncbi.nlm.nih.gov/pubmed/22132166", "http://www.ncbi.nlm.nih.gov/pubmed/21915282", "http://www.ncbi.nlm.nih.gov/pubmed/11302967", "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "http://www.ncbi.nlm.nih.gov/pubmed/10964697" ], "ideal_answer": [ "Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR. Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. Molecular genetic analyses have revealed that interactions between mutations in the genes encoding the RET receptor tyrosine kinase and the endothelin receptor type B (EDNRB) are central to the genesis of HSCR.", "Hirschsprung's disease (HSCR) is one the most common congenital intestinal disease, which leads to aganglionic megacolon in the early childhood. Several susceptibility genes have been identified, including RET protooncogene and its ligand, glial cell derived neutrophic factor (GDNF), Sox 10, Endothelin-3 (EDN3) and its receptor B (EDNRB). More specifically, EDNRB mutations are found in 5% of familial or sporadic HSCR." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10487", "http://www.uniprot.org/uniprot/EDNRB_MACFA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627", "http://www.uniprot.org/uniprot/EDNRB_MOUSE" ], "type": "yesno", "id": "551910c5622b194345000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "QTL analysis identifies a modifier locus of aganglionosis in the rat model of Hirschsprung disease carrying Ednrb(sl) mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132166", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 497, "text": "As reported previously, when the same null mutation of the Ednrb gene, Ednrb(sl), was introgressed into the F344 strain, almost 60% of F344-Ednrb(sl/sl) pups did not show any symptoms of aganglionosis, appearing healthy and normally fertile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915282", "endSection": "title" }, { "offsetInBeginSection": 325, "offsetInEndSection": 570, "text": "In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrb(sl) mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20009762", "endSection": "title" }, { "offsetInBeginSection": 330, "offsetInEndSection": 515, "text": "The aim of this study was to evaluate the implication of the EDN3 and EDNRB genes in a series of patients with Hirschsprung disease from Spain and determinate their mutational spectrum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20009762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16618617", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 382, "text": "Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16618617", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 408, "text": "Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15834508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15294878", "endSection": "title" }, { "offsetInBeginSection": 110, "offsetInEndSection": 319, "text": "Molecular genetic analyses have revealed that interactions between mutations in the genes encoding the RET receptor tyrosine kinase and the endothelin receptor type B (EDNRB) are central to the genesis of HSCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12574515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12355085", "endSection": "title" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1101, "text": "Thus, genetic interaction between mutations in RET and EDNRB is an underlying mechanism for this complex disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12355085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "EDNRB/EDN3 and Hirschsprung disease type II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11434563", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11302967", "endSection": "title" }, { "offsetInBeginSection": 133, "offsetInEndSection": 269, "text": "wo susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene and the endothelin B receptor (EDNRB) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1195, "text": "We conclude that Ednrb loss only in neural crest cells is sufficient to produce the Hirschsprungs disease phenotype observed with genomic Ednrb mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18693272", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 477, "text": "EDNRB mutations were detected in 2 of the 13 short-segment HD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14669347", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 995, "text": "The mutations of EDNRB gene and EDN-3 gene are found in the short-segment HD of sporadic Hirschsprung's disease in Chinese population, which suggests that the EDNRB gene and EDN-3 gene play important roles in the pathogenesis of HD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14669347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Functional characterization of three mutations of the endothelin B receptor gene in patients with Hirschsprung's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11471546", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 401, "text": "Hirschsprung's disease (HSCR) is one the most common congenital intestinal disease. It leads to aganglionic megacolon in the early childhood. Several susceptibility genes have been identified : RET protooncogene and its ligand, glial cell derived neutrophic factor (GDNF), Sox 10, Endothelin-3 (EDN3) and its receptor B (EDNRB). EDNRB mutations are found in 5% of familial or sporadic HSCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11471546", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 151, "text": "Enteric aganglionosis in Hirschsprung disease has been linked to genes coding for endothelin-3 (EDN3) and the endothelin B receptor (EDNRB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10792313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "To date, three genes have been identified as susceptibility genes for Hirschsprung's disease (HSCR), the RET proto-oncogene, the endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9094028", "endSection": "abstract" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1559, "text": "Our data indicate that RET and EDNRB mutations have a role in the aetiology of some sporadically occurring HSCR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9094028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Mutations of the endothelin-B receptor and endothelin-3 genes in Hirschsprung's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9035203", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3) have recently been recognized as susceptibility genes for Hirschsprung's disease (HD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9035203", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 682, "text": "These observations confirm that impaired function of the endothelin-B receptor or endothelin-3 is involved in the aetiology of some human HD cases. EDNRB mutations appear to be associated with short-segment HD, in contrast to RET mutations, which are found mainly in long-segment aganglionosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9035203", "endSection": "abstract" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1455, "text": "In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "QTL analysis identifies a modifier locus of aganglionosis in the rat model of Hirschsprung disease carrying Ednrb(sl) mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132166", "endSection": "title" }, { "offsetInBeginSection": 414, "offsetInEndSection": 568, "text": "Homozygous mutations in the endothelin-B receptor gene (EDNRB) on 13q22 have been identified in humans and mice with Hirschsprung disease type 2 (HSCR2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11484199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16618617", "endSection": "title" }, { "offsetInBeginSection": 267, "offsetInEndSection": 380, "text": "Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 725, "text": "These data might suggest that EDNRB mutations could be dosage sensitive: heterozygosity would predispose to isolated HSCR with incomplete penetrance, while homozygosity would result in more complex neurocristopathies associating HSCR and WS features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8852660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Highly recurrent RET mutations and novel mutations in genes of the receptor tyrosine kinase and endothelin receptor B pathways in Chinese patients with sporadic Hirschsprung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14633923", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 500, "text": "Mutations in genes encoding the RET receptor tyrosine kinase and endothelin receptor type B (EDNRB) are involved in HSCR pathogenesis; however, also important in ENS development are molecules that mediate events that are more restricted than those of RET and EDNRB, act later in development and which might not be HSCR-associated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20633936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Several missense mutations of the endothelin-B receptor (EDNRB) associated with Hirschsprung disease have recently been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10964697", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 982, "text": "These findings indicate that these missense mutations result in loss of function of EDNRB, and may provide the molecular pathological basis of Hirschsprung disease in some individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10964697", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 351, "text": "Manifestation of the disease has been linked to mutations in genes that encode the crucial signals for the development of the enteric nervous system-the RET and EDNRB signalling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12631670", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1465, "text": "In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10664228", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 288, "text": "In this study, we investigated whether germline mutations of endothelin receptor B (EDNRB), a gene involved in Hirschsprung disease (HSCR), could also predispose for malignant melanoma (MM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16145050", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 508, "text": "However, the similarity between the distal colonic aganglionosis in Hirschsprung disease and that due to EDN3 or EDNRB mutations led to the hypothesis that levels of expression of these genes might be affected in the absence of mutation, thus causing the Hirschsprung disease phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10792313", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1146, "text": "Our data strongly suggest that EDNRB is involved in predisposition for two different multigenic disorders, HSCR and melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16145050", "endSection": "abstract" } ] }, { "body": "What is known about the effectiveness of electronic food diaries ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24205807", "http://www.ncbi.nlm.nih.gov/pubmed/23415822", "http://www.ncbi.nlm.nih.gov/pubmed/20307404" ], "ideal_answer": [ "Electronic dietary records were better than food diaries in terms of fat percentage reduction in our trials, indicating that teledietetics increases healthy-eating awareness." ], "type": "summary", "id": "5502fe13e9bde69634000009", "snippets": [ { "offsetInBeginSection": 1617, "offsetInEndSection": 1791, "text": "Electronic dietary records were better than food diaries in terms of fat percentage reduction in our trials, indicating that teledietetics increases healthy-eating awareness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24205807", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 512, "text": "Nutrition monitoring is a relevant method to gain an overview of factors influencing health. However, keeping a food diary often constitutes a challenge for a patient, and developing a user-friendly and useful electronic food diary is not straightforward", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23415822", "endSection": "abstract" }, { "offsetInBeginSection": 2331, "offsetInEndSection": 3169, "text": "The analyzed apps reflected a variety of approaches to recording food intake and nutrition using different terminals--mostly mobile phones (35%), followed by PCs (29%) and PDAs (23%) for older studies, designed mainly for users with obesity (45%), diabetes mellitus (42%) and overweight (32%), or people who want to stay healthy (10%). The majority of the reviewed applications (67%) offered only input of food type and quantity. All approaches (n=31), except for two, relied on manual input of data, either by typing or by selecting a food type from a database. The exceptions (n=2) used a barcode scanning function. Users of mobile phone applications were not limited to data recording, but could view their data on the screen and send it via email. The tested web applications offered similar functionalities for recording food intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23415822", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 425, "text": "electronic food diary on a mobile phone that includes an energy balance visualization and computes and displays the difference between energy intake from food entries and energy expenditure from a multiple-sensor device that provides objective estimates of energy expenditure in real time", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20307404", "endSection": "abstract" } ] }, { "body": "Can the apoptosis regulator BAX trigger the release of cytochrome c?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25524600", "http://www.ncbi.nlm.nih.gov/pubmed/25619640", "http://www.ncbi.nlm.nih.gov/pubmed/22116711", "http://www.ncbi.nlm.nih.gov/pubmed/21307199", "http://www.ncbi.nlm.nih.gov/pubmed/23954445", "http://www.ncbi.nlm.nih.gov/pubmed/23567751", "http://www.ncbi.nlm.nih.gov/pubmed/25116390" ], "ideal_answer": [ "Yes, altered Bax conformation trigger its redistribution from the cytosol to mitochondria. Subsequently, cytochrome c is released from mitochondria to cytosol." ], "exact_answer": "yes", "type": "yesno", "id": "5717bacacb4ef8864c00000d", "snippets": [ { "offsetInBeginSection": 548, "offsetInEndSection": 684, "text": "6-Shogaol reduced the mitochondrial membrane potential (MMP) and released cytochrome c from mitochondria to cytosol via Bax activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25619640", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 676, "text": "Moreover, overexpression of ER\u03b2 prevented Bax activation, cytochrome c release, caspase-3 activation, and PARP cleavage during apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25524600", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 573, "text": "In this study, we demonstrated that EV71 infection altered Bax conformation and triggered its redistribution from the cytosol to mitochondria in RD cells. Subsequently, cytochrome c was released from mitochondria to cytosol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116390", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1218, "text": "associated with translocation of Bax from the cytosol to the mitochondrial membrane, cytochrome c release, and caspase activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954445", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 397, "text": "Once activated, BAK and BAX form proteolipid pores in the OMM leading to mitochondrial outer membrane permeabilization (MOMP), and the release of inner membrane space proteins, such as cytochrome c, which promotes caspase activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567751", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 809, "text": " Our results showed that OC induced a caspase-dependent apoptosis by triggering a series of events in HeLa cells including Bax translocation, cytochrome c release, caspase-3 activation, chromosome fragmentation followed by caspase-8 activation, Bid cleavage and eventually cell death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22116711", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 411, "text": "Bax plays a key role in intrinsic apoptotic signaling in neurons by allowing the release of mitochondrial cytochrome c. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21307199", "endSection": "abstract" } ] }, { "body": "Which biological process in known as Endoplasmic Reticulum-Associated Protein Degradation (ERAD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10906272", "http://www.ncbi.nlm.nih.gov/pubmed/8943015", "http://www.ncbi.nlm.nih.gov/pubmed/15618412", "http://www.ncbi.nlm.nih.gov/pubmed/21135095", "http://www.ncbi.nlm.nih.gov/pubmed/21871892", "http://www.ncbi.nlm.nih.gov/pubmed/24817869", "http://www.ncbi.nlm.nih.gov/pubmed/23907667", "http://www.ncbi.nlm.nih.gov/pubmed/17727818", "http://www.ncbi.nlm.nih.gov/pubmed/11139575", "http://www.ncbi.nlm.nih.gov/pubmed/16573238", "http://www.ncbi.nlm.nih.gov/pubmed/21945179", "http://www.ncbi.nlm.nih.gov/pubmed/20038635", "http://www.ncbi.nlm.nih.gov/pubmed/12641210", "http://www.ncbi.nlm.nih.gov/pubmed/22812526", "http://www.ncbi.nlm.nih.gov/pubmed/11359923", "http://www.ncbi.nlm.nih.gov/pubmed/17872946", "http://www.ncbi.nlm.nih.gov/pubmed/23236186", "http://www.ncbi.nlm.nih.gov/pubmed/16573235", "http://www.ncbi.nlm.nih.gov/pubmed/20219571", "http://www.ncbi.nlm.nih.gov/pubmed/12121416", "http://www.ncbi.nlm.nih.gov/pubmed/16565503", "http://www.ncbi.nlm.nih.gov/pubmed/22119785", "http://www.ncbi.nlm.nih.gov/pubmed/11756557", "http://www.ncbi.nlm.nih.gov/pubmed/15464997", "http://www.ncbi.nlm.nih.gov/pubmed/23018488", "http://www.ncbi.nlm.nih.gov/pubmed/15571817" ], "ideal_answer": [ "Endoplasmic reticulum-associated protein degradation (ERAD) is the quality control system in the endoplasmic reticulum of eukaryotic cells which ensures that newly synthesized proteins that fail to fold into the correct conformation or unassembled orphan subunits of oligomeric proteins are rapidly eliminated by proteolytic degradation. This entails the export of proteins from the endoplasmic reticulum to the cytosol followed by their destruction by the cytosolic ubiquitin/proteasome pathway. While this mechanism effectively prevents the cellular accumulation of non-functional or unwanted endogenous proteins, it renders the cell vulnerable to certain viruses and toxins that are able to subvert this degradative mechanism for their own advantage.", "In the secretory pathway, quality control for the correct folding of proteins is largely occurring in the endoplasmic reticulum (ER), at the earliest possible stage and in an environment where early folding intermediates mix with terminally misfolded species. An elaborate cellular mechanism aims at dividing the former from the latter and promotes the selective transport of misfolded species back into the cytosol, a step called retrotranslocation. During retrotranslocation proteins will become ubiquitinated on the cytosolic side of the ER membrane by dedicated machineries and will be targeted to the proteasome for degradation. The entire process, from protein recognition to final degradation, has been named ER-associated protein degradation, or simply ERAD. " ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004721", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055694", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060746", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005783" ], "type": "summary", "id": "54fc27a896abe38008000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Endoplasmic reticulum-associated protein degradation (ERAD) removes improperly-folded proteins from the ER membrane into the cytosol where they undergo proteasomal degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 766, "text": "In the secretory pathway, quality control for the correct folding of proteins is largely occurring in the endoplasmic reticulum (ER), at the earliest possible stage and in an environment where early folding intermediates mix with terminally misfolded species. An elaborate cellular mechanism aims at dividing the former from the latter and promotes the selective transport of misfolded species back into the cytosol, a step called retrotranslocation. During retrotranslocation proteins will become ubiquitinated on the cytosolic side of the ER membrane by dedicated machineries and will be targeted to the proteasome for degradation. The entire process, from protein recognition to final degradation, has been named ER-associated protein degradation, or simply ERAD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22812526", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 820, "text": "From the many cellular processes, Cdc48 is involved in, its function in endoplasmic reticulum associated protein degradation (ERAD) is understood best. This quality control process for proteins of the secretory pathway scans protein folding and discovers misfolded proteins in the endoplasmic reticulum (ER), the organelle, destined for folding of these proteins and their further delivery to their site of action. Misfolded lumenal and membrane proteins of the ER are detected by chaperones and lectins and retro-translocated out of the ER for degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21945179", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1169, "text": "After polyubiquitylation of the protein substrate, Cdc48 together with its dimeric co-factor complex Ufd1-Npl4 pulls the misfolded protein out and away from the ER membrane and delivers it to down-stream components for degradation by a cytosolic proteinase machine, the proteasome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21945179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 822, "text": "Recognition and elimination of misfolded proteins are essential cellular processes. More than thirty percent of the cellular proteins are proteins of the secretory pathway. They fold in the lumen or membrane of the endoplasmic reticulum from where they are sorted to their site of action. The folding process, as well as any refolding after cell stress, depends on chaperone activity. In case proteins are unable to acquire their native conformation, chaperones with different substrate specificity and activity guide them to elimination. For most misfolded proteins of the endoplasmic reticulum this requires retro-translocation to the cytosol and polyubiquitylation of the misfolded protein by an endoplasmic reticulum associated machinery. Thereafter ubiquitylated proteins are guided to the proteasome for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway eliminates aberrant proteins from the ER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Terminally misfolded or unassembled proteins are degraded by the cytoplasmic ubiquitin-proteasome pathway in a process known as ERAD (endoplasmic reticulum-associated protein degradation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17727818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 603, "text": "Endoplasmic reticulum-associated protein degradation (ERAD) is a protein quality control mechanism that minimizes the detrimental effects of protein misfolding in the secretory pathway. Molecular chaperones and ER lumenal lectins are essential components of this process because they maintain the solubility of unfolded proteins and can target ERAD substrates to the cytoplasmic proteasome. Other factors are likely required to aid in the selection of ERAD substrates, and distinct proteinaceous machineries are required for substrate retrotranslocation/dislocation from the ER and proteasome targeting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16573235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "The endoplasmic reticulum (ER) quality control processes recognize and remove aberrant proteins from the secretory pathway. Several variants of the plasma protein fibrinogen are recognized as aberrant and degraded by ER-associated protein degradation (ERAD), thus leading to hypofibrinogenemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16565503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 463, "text": "The endoplasmic reticulum (ER) is the eukaryotic organelle where most secretory proteins are folded for subsequent delivery to their site of action. Proper folding of newly synthesized proteins is monitored by a stringent ER quality control system. This system recognizes misfolded or unassembled proteins and prevents them from reaching their final destination. Instead, they are extracted from the ER, polyubiquitinated and degraded by the cytosolic proteasome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15571817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Endoplasmic reticulum (ER) stress, which is caused by the accumulation of misfolded proteins in the ER, elicits an adaptive response, the unfolded protein response (UPR). One component of the UPR, the endoplasmic reticulum-associated protein degradation (ERAD) system, has an important function in the survival of ER stressed cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15464997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 825, "text": "Proteins that fail to fold properly as well as constitutive or regulated short-lived proteins of the endoplasmatic reticulum (ER) are subjected to proteolysis by cytosolic 26 S proteasomes. This process, termed ER-associated protein degradation (ERAD), has also been implicated in the generation of some important human disorders, for example, cystic fibrosis. To become accessible to the proteasome, ERAD substrates must first be retrogradely transported from the ER into the cytosol, in a process termed dislocation. Surprisingly, protein dislocation from the ER seems to require at least some components that also mediate import into this compartment. Moreover, polyubiquitination of ERAD substrates at the ER membrane as well as the cytoplasmic Cdc48p/Npl4p/Ufd1p complex were shown to contribute to this export reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12641210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 537, "text": "Proteins that fail to fold properly as well as constitutive or regulated short-lived proteins of the endoplasmic reticulum are subjected to proteolysis by cytosolic 26S proteasomes. This process is known as endoplasmic reticulum-associated protein degradation. In order to become accessible to the proteasome of this system substrates must first be retrogradely transported from the endoplasmic reticulum into the cytosol, in a process termed dislocation. This export step seems to be accompanied by polyubiquitination of such molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12121416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Endoplasmic reticulum-associated degradation (ERAD) disposes of aberrant proteins in the secretory pathway. Protein substrates of ERAD are dislocated via the Sec61p translocon from the endoplasmic reticulum to the cytosol, where they are ubiquitinated and degraded by the proteasome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11756557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Membrane and secretory proteins fold in the endoplasmic reticulum (ER), and misfolded proteins may be retained and targeted for ER-associated protein degradation (ERAD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11359923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 693, "text": "The endoplasmic reticulum contains a protein quality control system that discovers malfolded or unassembled secretory proteins and subjects them to degradation in the cytosol. This requires retrograde transport of the respective proteins from the endoplasmic reticulum back to the cytosol via the Sec61 translocon. In addition, a fully competent ubiquitination machinery and the 26 S proteasome are necessary for retrotranslocation and degradation. Ubiquitination of mutated and malfolded proteins of the endoplasmic reticulum is dependent mainly on the ubiquitin-conjugating enzyme Ubc7p. In addition, several new membrane components of the endoplasmic reticulum are required for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11139575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 684, "text": "The quality control system in the endoplasmic reticulum of eukaryotic cells ensures that newly synthesized proteins that fail to fold into the correct conformation or unassembled orphan subunits of oligomeric proteins are rapidly eliminated by proteolytic degradation. This entails the export of proteins from the endoplasmic reticulum to the cytosol followed by their destruction by the cytosolic ubiquitin/proteasome pathway. While this mechanism effectively prevents the cellular accumulation of non-functional or unwanted endogenous proteins, it renders the cell vulnerable to certain viruses and toxins that are able to subvert this degradative mechanism for their own advantage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10906272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Endoplasmic reticulum-associated protein degradation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10906272", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "Until recently, the degradation of aberrant and unassembled proteins retained in the endoplasmic reticulum (ER) was thought to involve unidentified ER-localized proteases. We now show that the ER-associated degradation (ERAD) of two mutant proteins that accumulate in the ER lumen is inhibited in a proteasome-defective yeast strain and when cytosol from this mutant is used in an in vitro assay. In addition, ERAD is limited in vitro in the presence of the proteasome inhibitors, 3,4-dichloroisocoumarin and lactacystin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8943015", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 868, "text": "We conclude that lumenal ERAD substrates are exported from the yeast ER to the cytoplasm for degradation by the proteasome complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8943015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Misfolded proteins in the endoplasmic reticulum (ER) are eliminated by a process known as ER-associated degradation (ERAD), which starts with misfolded protein recognition, followed by ubiquitination, retrotranslocation to the cytosol, deglycosylation, and targeting to the proteasome for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17872946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23236186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Proteins that fail to correctly fold or assemble into oligomeric complexes in the endoplasmic reticulum (ER) are degraded by a ubiquitin- and proteasome-dependent process known as ER-associated degradation (ERAD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22119785", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 322, "text": "Proteins that cannot fold properly will be directed to a process known as endoplasmic reticulum associated degradation (ERAD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21871892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Endoplasmic reticulum-associated degradation (ERAD) is an essential quality control process whereby misfolded proteins are exported from the endoplasmic reticulum and degraded by the proteasome in the cytosol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21135095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Quality control mechanisms in the endoplasmic reticulum prevent deployment of aberrant or unwanted proteins to distal destinations and target them to degradation by a process known as endoplasmic reticulum-associated degradation, or ERAD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16573238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Proteins that fail to fold in the endoplasmic reticulum (ER) or cannot find a pattern for assembly are often disposed of by a process named ER-associated degradation (ERAD), which involves transport of the substrate protein across the ER membrane (dislocation) followed by rapid proteasome-mediated proteolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15618412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Quality control mechanisms in the endoplasmic reticulum prevent deployment of aberrant or unwanted proteins to distal destinations and target them to degradation by a process known as endoplasmic reticulum-associated degradation, or ERAD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16573238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Misfolded proteins in the endoplasmic reticulum (ER) are eliminated by a process known as ER-associated degradation (ERAD), which starts with misfolded protein recognition, followed by ubiquitination, retrotranslocation to the cytosol, deglycosylation, and targeting to the proteasome for degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17872946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Misfolded proteins in the endoplasmic reticulum (ER) are dislocated out of the ER to the cytosol, polyubiquitinated, and degraded by the ubiquitin-proteasome system in a process collectively termed ER-associated degradation (ERAD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23018488", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 688, "text": "Eukaryotic organisms have evolved a highly conserved endoplasmic reticulum-mediated protein quality control (ERQC) mechanism to monitor folding processes of secretory and membrane proteins, allowing export of only correctly folded proteins to their physiological destinations, retaining incompletely/mis-folded ones in the ER for additional folding attempts, marking and removing terminally misfolded ones via a unique multiple-step degradation process known as ER-associated degradation (ERAD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24817869", "endSection": "abstract" } ] }, { "body": "List BRAF inhibitors that have been tested in clinical trials for treatment of melanoma patients", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24456413", "http://www.ncbi.nlm.nih.gov/pubmed/21639808", "http://www.ncbi.nlm.nih.gov/pubmed/24291778", "http://www.ncbi.nlm.nih.gov/pubmed/23094782", "http://www.ncbi.nlm.nih.gov/pubmed/23621583", "http://www.ncbi.nlm.nih.gov/pubmed/22804352", "http://www.ncbi.nlm.nih.gov/pubmed/24720932", "http://www.ncbi.nlm.nih.gov/pubmed/23403819", "http://www.ncbi.nlm.nih.gov/pubmed/23788912", "http://www.ncbi.nlm.nih.gov/pubmed/23833299", "http://www.ncbi.nlm.nih.gov/pubmed/22382362", "http://www.ncbi.nlm.nih.gov/pubmed/22431777", "http://www.ncbi.nlm.nih.gov/pubmed/23020132", "http://www.ncbi.nlm.nih.gov/pubmed/25056920", "http://www.ncbi.nlm.nih.gov/pubmed/22306669", "http://www.ncbi.nlm.nih.gov/pubmed/25287827", "http://www.ncbi.nlm.nih.gov/pubmed/24295639", "http://www.ncbi.nlm.nih.gov/pubmed/23918947", "http://www.ncbi.nlm.nih.gov/pubmed/24616537", "http://www.ncbi.nlm.nih.gov/pubmed/25488880", "http://www.ncbi.nlm.nih.gov/pubmed/22594466", "http://www.ncbi.nlm.nih.gov/pubmed/25037139", "http://www.ncbi.nlm.nih.gov/pubmed/24463460", "http://www.ncbi.nlm.nih.gov/pubmed/22350184", "http://www.ncbi.nlm.nih.gov/pubmed/23569304", "http://www.ncbi.nlm.nih.gov/pubmed/22332713", "http://www.ncbi.nlm.nih.gov/pubmed/23795808", "http://www.ncbi.nlm.nih.gov/pubmed/23116250", "http://www.ncbi.nlm.nih.gov/pubmed/22253555", "http://www.ncbi.nlm.nih.gov/pubmed/25265494", "http://www.ncbi.nlm.nih.gov/pubmed/24325952", "http://www.ncbi.nlm.nih.gov/pubmed/24408395", "http://www.ncbi.nlm.nih.gov/pubmed/24333389", "http://www.ncbi.nlm.nih.gov/pubmed/24080641", "http://www.ncbi.nlm.nih.gov/pubmed/23251089", "http://www.ncbi.nlm.nih.gov/pubmed/22356324", "http://www.ncbi.nlm.nih.gov/pubmed/22194965", "http://www.ncbi.nlm.nih.gov/pubmed/24958825", "http://www.ncbi.nlm.nih.gov/pubmed/24121489", "http://www.ncbi.nlm.nih.gov/pubmed/23326492", "http://www.ncbi.nlm.nih.gov/pubmed/21505227", "http://www.ncbi.nlm.nih.gov/pubmed/22394203", "http://www.ncbi.nlm.nih.gov/pubmed/25040674", "http://www.ncbi.nlm.nih.gov/pubmed/24259661", "http://www.ncbi.nlm.nih.gov/pubmed/22651703" ], "ideal_answer": [ "Vemurafenib and dabrafenib are BRAF inhibitors that have been tested in clinical trials for treatment of melanoma patients." ], "exact_answer": [ [ "Vemurafenib" ], [ "Dabrafenib" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1909" ], "type": "list", "id": "54d8d60d014675820d000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-agent BRAF inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287827", "endSection": "title" }, { "offsetInBeginSection": 482, "offsetInEndSection": 732, "text": " Here, we report patients treated with combination therapy after disease progression with BRAF inhibitor treatment administered before study enrollment (part B; n = 26) or after cross-over at progression with dabrafenib monotherapy (part C; n = 45). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287827", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 335, "text": "This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25265494", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 658, "text": "METHODS: All patients treated with the BRAF inhibitors vemurafenib or dabrafenib or combination BRAF inhibitor and mitogen-activated protein kinase kinase (MEK) inhibitor therapy at Westmead Hospital, Sydney, Australia underwent regular dermatological assessments for the duration of therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25040674", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 394, "text": "We assessed the safety and efficacy of combined BRAF inhibition with vemurafenib and MEK inhibition with cobimetinib in patients with advanced BRAF-mutated melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25037139", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 598, "text": "We included individuals who had either recently progressed on vemurafenib or never received a BRAF inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25037139", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1181, "text": "However, it is becoming evident that the effects of paradoxical mitogen-activated protein kinase pathway activation by BRAF inhibitors in non-BRAF-mutant cells needs to be taken into account, which may be implicated in the problems encountered in the first clinical trial testing a combination of the BRAF inhibitor vemurafenib with ipilimumab (anti-CTLA4), with significant liver toxicities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24958825", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 641, "text": "The BRAF inhibitor dabrafenib recently was approved for use in patients with BRAF V600-mutated metastatic melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24720932", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 575, "text": "His treatment course to date has included surgery, adjuvant radiotherapy, and interferon, metastasectomies, granulocyte-macrophage colony-stimulating factors, a clinical trial with the BRAF inhibitor vemurafenib (PLX-4032), clinical trial with combination BRAF plus MEK inhibition with vemurafenib plus GDC-0973, and combination targeted and immune therapy with vemurafenib plus the anti-CTLA4 antibody ipilimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24616537", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 739, "text": "Thirty-one patients commenced dabrafenib therapy including six individuals who had progressed on a prior BRAF-inhibitor treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24463460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24408395", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Dabrafenib is a BRAF kinase inhibitor indicated for the treatment of BRAF V600E mutation-positive melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24408395", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 475, "text": "This was a prospective study of melanoma patients harboring the BRAF V600 mutation and treated with iBRAF within a clinical trial (dabrafenib) or as part of an expanded access program (vemurafenib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24333389", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 236, "text": "We investigated the BRAF kinase inhibitor vemurafenib in patients with advanced melanoma with symptomatic brain metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295639", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 900, "text": "This discovery led to the development of BRAF kinase inhibitors like vemurafenib and dabrafenib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259661", "endSection": "abstract" }, { "offsetInBeginSection": 1524, "offsetInEndSection": 1718, "text": "CONCLUSIONS: Dabrafenib joins vemurafenib to confirm the superior clinical outcome of the BRAF inhibitors when compared with dacarbazine in patients with BRAF(V600E)-positive advanced melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Tumor genetic analyses of patients with metastatic melanoma treated with the BRAF inhibitor dabrafenib (GSK2118436).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23833299", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "PURPOSE: Dabrafenib is a selective inhibitor of V600-mutant BRAF kinase, which recently showed improved progression-free survival (PFS) as compared with dacarbazine, in metastatic melanoma patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23833299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918947", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "PURPOSE: Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Cutaneous squamous cell carcinoma (cSCC) is a concerning toxicity with BRAF inhibitors in the treatment for melanoma. While the two drugs shown to improve survival, vemurafenib, and dabrafenib, have similar efficacy, the reported rates of cSCC are quite different.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23795808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "PURPOSE To assess pharmacodynamic effects and intrinsic and acquired resistance mechanisms of the BRAF inhibitor vemurafenib in BRAF(V600)-mutant melanoma, leading to an understanding of the mechanism of action of vemurafenib and ultimately to optimization of metastatic melanoma therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23569304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "BACKGROUND: The cobas 4800 BRAF V600 Mutation Test is a CE-marked and FDA-approved in vitro diagnostic assay used to select patients with metastatic melanoma for treatment with the selective BRAF inhibitor vemurafenib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The purpose of this study is to review the development of BRAF inhibitors, with emphasis on the trials conducted with dabrafenib (GSK2118436) and the evolving role of dabrafenib in treatment for melanoma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23251089", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 477, "text": "Dabrafenib inhibits the mutant BRAF (BRAF(mut)) protein in melanomas with BRAF(V600E) and BRAF(V600K) genotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23251089", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 333, "text": "To address this problem, we conducted a phase 1 and 2 trial of combined treatment with dabrafenib, a selective BRAF inhibitor, and trametinib, a selective MAPK kinase (MEK) inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23020132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22804352", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 392, "text": "We conducted a systematic prospective dermatological review of all patients enrolled at a single institution in the phase I/II clinical trial of the mutant BRAF inhibitor dabrafenib (GSK2118436).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22804352", "endSection": "abstract" }, { "offsetInBeginSection": 1768, "offsetInEndSection": 1959, "text": "CONCLUSIONS: Administration of the mutant BRAF inhibitor dabrafenib is associated with induction of keratinocytic proliferation, which in some cases develops features of low-grade malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22804352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Neoplastic leptomeningitis presenting in a melanoma patient treated with dabrafenib (a V600EBRAF inhibitor): a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22594466", "endSection": "title" }, { "offsetInBeginSection": 854, "offsetInEndSection": 992, "text": "For this reason, she was enrolled into another clinical trial with the GSK2118436 BRAF inhibitor, dabrafenib, as a second line of therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22594466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND: The development of keratoacanthomas (KAs) and well-differentiated squamous cell carcinomas (SCCs) is a known adverse effect of novel BRAF inhibitors such as vemurafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431777", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 548, "text": "OBSERVATIONS: We describe a patient with stage IV melanoma who received the BRAF inhibitor vemurafenib (recently approved by the US Food and Drug Administration) as part of a clinical trial and developed numerous diffuse, pathology-proven KAs and SCCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431777", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1046, "text": "CONCLUSIONS: Given vemurafenib's recent approval by the US Food and Drug Administration, we provide a timely case report on the effective use of PDT in the treatment of BRAF inhibitor-associated KAs and SCCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431777", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 374, "text": "The BRAF inhibitor, vemurafenib, has shown up to 78% objective response rates in melanoma patients harboring the BRAF-V600E mutation but not in patients lacking the mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22382362", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 338, "text": "The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22356324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "CONTEXT: A polymerase chain reaction-based companion diagnostic (cobas 4800 BRAF V600 Mutation Test) was recently approved by the US Food and Drug Administration to select patients with BRAF-mutant metastatic melanoma for treatment with the BRAF inhibitor vemurafenib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332713", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 397, "text": "However, in the recent clinical trial of the BRAF inhibitor, vemurafenib (PLX4032), a significant percentage of BRAF V600E mutant melanoma patients did not meet the RECIST criteria for a response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505227", "endSection": "abstract" }, { "offsetInBeginSection": 48, "offsetInEndSection": 280, "text": "Vemurafenib (RG7204/PLX4032), a small-molecule inhibitor of mutant BRAF, has shown striking clinical efficacy in BRAFV600 mutant melanoma, creating the need for a well-validated companion diagnostic to select patients for treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22306669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "BACKGROUND: Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21639808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Vemurafenib is the first molecularly targeted therapy to be licensed in the US and Europe for treatment of advanced melanoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116250", "endSection": "abstract" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1747, "text": "Clinical trials to test the efficacy of vemurafenib in combination with immunomodulatory agents, such as ipilimumab, and MAPK kinase (MEK) inhibitors, such as GDC-0973, in the treatment of advanced melanoma are currently underway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116250", "endSection": "abstract" } ] }, { "body": "which are the risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23990187", "http://www.ncbi.nlm.nih.gov/pubmed/15929624", "http://www.ncbi.nlm.nih.gov/pubmed/18221594", "http://www.ncbi.nlm.nih.gov/pubmed/17652294", "http://www.ncbi.nlm.nih.gov/pubmed/19850699", "http://www.ncbi.nlm.nih.gov/pubmed/21475680", "http://www.ncbi.nlm.nih.gov/pubmed/9761089", "http://www.ncbi.nlm.nih.gov/pubmed/19791461", "http://www.ncbi.nlm.nih.gov/pubmed/23500286", "http://www.ncbi.nlm.nih.gov/pubmed/23867451", "http://www.ncbi.nlm.nih.gov/pubmed/17162272", "http://www.ncbi.nlm.nih.gov/pubmed/15856398", "http://www.ncbi.nlm.nih.gov/pubmed/7787270", "http://www.ncbi.nlm.nih.gov/pubmed/18033231", "http://www.ncbi.nlm.nih.gov/pubmed/2482379", "http://www.ncbi.nlm.nih.gov/pubmed/20118111", "http://www.ncbi.nlm.nih.gov/pubmed/20132378", "http://www.ncbi.nlm.nih.gov/pubmed/19419401", "http://www.ncbi.nlm.nih.gov/pubmed/22762717", "http://www.ncbi.nlm.nih.gov/pubmed/10957787", "http://www.ncbi.nlm.nih.gov/pubmed/19699347" ], "ideal_answer": [ "The following risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy have been identified: 1) previous cardiac arrest; 2) sustained ventricular tachycardia; 3) family history of sudden cardiac death; 4) high-risk genetic mutations; 5) unexplained syncope; 6) non-sustained ventricular tachycardia; 7) hypotensive response to exercise; 8) marked left ventricular hypertrophy; 9) J-wave on ECG and 10) myocardial fibrosis using late gadolinium enhancement" ], "exact_answer": [ [ "myocardial fibrosis using late gadolinium enhancement" ], [ "J-wave on ECG" ], [ "Extreme left ventricular hypertrophy (>30mm)" ], [ "Nonsustained ventricular tachycardia" ], [ "Sustained ventricular tachycardia" ], [ "previous cardiac arrest" ], [ "family history of sudden cardiac death" ], [ "unexplained syncope" ], [ "hypotensive response to exercise" ], [ "high-risk genetic mutations" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016757", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012307" ], "type": "list", "id": "531375a6e3eabad021000011", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 273, "text": "Cardiac magnetic resonance (CMR) is used in the diagnosis and risk stratification of hypertrophic cardiomyopathy (HCM) and can detect myocardial replacement fibrosis (anindependent predictor of adverse cardiac outcomes) using late gadolinium enhancement (LGE). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "J wave is associated with increased risk of sudden cardiac arrest in patients with hypertrophic cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23867451", "endSection": "title" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1023, "text": "The J wave may be a risk factor for SCA in patients with HCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23867451", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1745, "text": "Extreme left ventricular hypertrophy was the most common risk factor present (alone or in combination with other markers) in patients experiencing primary prevention interventions (17 of 26 [65%]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23500286", "endSection": "abstract" }, { "offsetInBeginSection": 2024, "offsetInEndSection": 2123, "text": "Extreme left ventricular hypertrophy was most frequently associated with appropriate interventions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23500286", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 918, "text": "In conclusion, it is demonstrated that LGE has incremental value in addition to clinical risk factors for risk stratification and management of patients with HC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22762717", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1196, "text": "Fibrosis as detected by CMR should be evaluated as an additional risk factor to further delineate risk of SCD in carriers of an HCM causing mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21475680", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1119, "text": "Nonsustained VT was the only predictive risk factor (RF) for an appropriate ICD intervention in the PP (positive predictive value 22%, negative predictive value 96%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20132378", "endSection": "abstract" }, { "offsetInBeginSection": 1541, "offsetInEndSection": 1648, "text": "Nonsustained ventricular tachycardia seems to be the most predictive RF for appropriate device discharges. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20132378", "endSection": "abstract" }, { "offsetInBeginSection": 2427, "offsetInEndSection": 2709, "text": "However, LGE was strongly associated with surrogates of arrhythmia and remained a significant associate of subsequent SCD and/or ICD discharge after controlling for other variables. If replicated, LGE may be considered an important risk factor for sudden death in patients with HCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19850699", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1415, "text": "In conclusion, our cohort study results do not support LVOTO as an independent risk factor for SD in patients with hypertrophic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19699347", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1433, "text": "The appearance of a \"hump\" at the ST segment during exercise testing appears to be a risk factor for SCD in patients with HCM. However, further studies are necessary to validate this finding in larger populations and to elucidate the mechanism of the appearance of the \"hump.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19419401", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 667, "text": "The ICD is definitely indicated for secondary prevention of sudden death in patients with HCM who have survived a cardiac arrest with documented ventricular fibrillation, or experienced one or more episodes of sustained ventricular tachycardia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18221594", "endSection": "abstract" }, { "offsetInBeginSection": 786, "offsetInEndSection": 1207, "text": "A number of risk markers are used to assess the magnitude of risk, including family history of premature sudden death; extreme left ventricular (LV) hypertrophy (> 30 mm) in young patients; nonsustained ventricular tachycardia on Holter electrocardiographic recording; unexplained (not neurally mediated) syncope, particularly in young patients; and blood pressure decrease or inadequate increase during upright exercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18221594", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 962, "text": "Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652294", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1311, "text": "The following risk factors were analyzed: 1) previous cardiac arrest or sustained ventricular tachycardia; 2) family history of sudden cardiac death; 3) high-risk genetic mutations; 4) syncope; 5) non-sustained ventricular tachycardia; 6) hypotensive response to exercise; and 7) marked left ventricular hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15929624", "endSection": "abstract" }, { "offsetInBeginSection": 1809, "offsetInEndSection": 1989, "text": "Family history of sudden death was associated with a positive predictive value of 25% for appropriate therapies, 40% for syncope and 50% for non-sustained ventricular tachycardia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15929624", "endSection": "abstract" }, { "offsetInBeginSection": 2592, "offsetInEndSection": 2768, "text": "In patients with an implantable cardioverter-defibrillator for primary prevention, non-sustained ventricular tachycardia was the risk factor with the highest predictive value. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15929624", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1377, "text": "It is concluded that there is an association of the mutation Arg719Trp in the beta-myosin heavy chain with sudden cardiac death in a young child. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10957787", "endSection": "abstract" } ] }, { "body": "What is known about the economic cost of urinary incontinence?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12809878", "http://www.ncbi.nlm.nih.gov/pubmed/23369111", "http://www.ncbi.nlm.nih.gov/pubmed/24198618", "http://www.ncbi.nlm.nih.gov/pubmed/11183903", "http://www.ncbi.nlm.nih.gov/pubmed/22500250", "http://www.ncbi.nlm.nih.gov/pubmed/9510336", "http://www.ncbi.nlm.nih.gov/pubmed/11386591" ], "ideal_answer": [ "The estimated total economic cost in treating overactive bladder was 117 billion Korean Won (KRW, the currency of South Koea) in 2006 and 145 billion KRW in 2007. The estimated total cost in treating stress urinary incontinence was 122 billion KRW in 2006 and 59 billion KRW in 2007.\nThe estimated total economic cost of OAB was 12.02 billion dollars in 2000, with 9.17 and 2.85 billion dollars incurred in the community and institutions, respectively. Community female and male OAB costs totaled 7.37 and 1.79 billion dollars, respectively. The estimated total cost was sensitive to the estimated prevalence of OAB; therefore, we calculated the average cost per community-dwelling person with OAB, which was 267 dollars per year.\nAn estimated 1835628 community-dwelling women over the age of 18 years had urinary incontinence in 1998. The total annual cost of this urinary incontinence is estimated at $710.44 million, or $387 per incontinent woman, comprising $338.47 million in treatment costs and $371.97 million in personal costs. An estimated 60% of women with incontinence in 1998 were aged 40 years or over. Assuming the prevalence of incontinence remains constant and, allowing for inflation, we project that the total annual cost in 20 years' time will be $1267.85 million, 93% ($1.18 billion) of which will constitute costs associated with women aged over 40 years.\nFor individuals 65 years of age and older these costs are substantial, increasing from $8.2 billion (1984 dollars) to $16.4 billion (1993 dollars). The 1995 societal cost of incontinence for individuals aged 65 years and older was $26.3 billion, or $3565 per individual with urinary incontinence." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004469", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014549", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017048", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004470", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014551", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014550", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053207", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053202", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001745", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017281", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017721", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003365", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014570" ], "type": "summary", "id": "5335c938d6d3ac6a34000052", "snippets": [ { "offsetInBeginSection": 1581, "offsetInEndSection": 1634, "text": "urgency UI also results in substantial economic costs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23369111", "endSection": "abstract" }, { "offsetInBeginSection": 1739, "offsetInEndSection": 1796, "text": "substantial economic burden attributable to UI due to NDO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23369111", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 806, "text": "The estimated total economic cost in treating overactive bladder was 117 billion Korean Won (KRW, the currency of South Koea) in 2006 and 145 billion KRW in 2007. The estimated total cost in treating stress urinary incontinence was 122 billion KRW in 2006 and 59 billion KRW in 2007.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22500250", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 275, "text": "OAB may severely impair quality of life, and its overall economic costs to society are substantial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198618", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1372, "text": "The estimated total economic cost of OAB was 12.02 billion dollars in 2000, with 9.17 and 2.85 billion dollars incurred in the community and institutions, respectively. Community female and male OAB costs totaled 7.37 and 1.79 billion dollars, respectively. The estimated total cost was sensitive to the estimated prevalence of OAB; therefore, we calculated the average cost per community-dwelling person with OAB, which was 267 dollars per year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12809878", "endSection": "abstract" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1681, "text": "The conservative estimates of the total cost of OAB were comparable to those of osteoporosis and gynecologic and breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12809878", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 1133, "text": "An estimated 1835628 community-dwelling women over the age of 18 years had urinary incontinence in 1998. The total annual cost of this urinary incontinence is estimated at $710.44 million, or $387 per incontinent woman, comprising $338.47 million in treatment costs and $371.97 million in personal costs. An estimated 60% of women with incontinence in 1998 were aged 40 years or over. Assuming the prevalence of incontinence remains constant and, allowing for inflation, we project that the total annual cost in 20 years' time will be $1267.85 million, 93% ($1.18 billion) of which will constitute costs associated with women aged over 40 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11386591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Overactive bladder (OAB) is a highly prevalent condition among older patients, and its presence is associated with the use of substantial healthcare resources and economic costs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11183903", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1021, "text": "Caring for incontinent patients in the long-term care setting was shown to result in substantial additional costs,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11183903", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 270, "text": "For individuals 65 years of age and older these costs are substantial, increasing from $8.2 billion (1984 dollars) to $16.4 billion (1993 dollars). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9510336", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 565, "text": "The 1995 societal cost of incontinence for individuals aged 65 years and older was $26.3 billion, or $3565 per individual with urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9510336", "endSection": "abstract" } ] }, { "body": "Which are the coactivators of the Yes-associated protein (yap)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22632831", "http://www.ncbi.nlm.nih.gov/pubmed/16332960", "http://www.ncbi.nlm.nih.gov/pubmed/23380592", "http://www.ncbi.nlm.nih.gov/pubmed/23985334", "http://www.ncbi.nlm.nih.gov/pubmed/25097035", "http://www.ncbi.nlm.nih.gov/pubmed/20439427" ], "ideal_answer": [ "The Yap protein forms complex with Tead (TEA domain) transcription factors." ], "exact_answer": [ "Tead (TEA domain) transcription factors." ], "type": "factoid", "id": "56d1e23c67f0cb3d66000009", "snippets": [ { "offsetInBeginSection": 264, "offsetInEndSection": 675, "text": "ndependent research, often in the context of muscle biology, described Tead (TEA domain) transcription factors, which bind CATTCC DNA motifs to regulate gene expression. These two research areas were joined by the finding that the Hippo pathway regulates the activity of Tead transcription factors mainly through phosphorylation of the transcriptional coactivators Yap and Taz, which bind to and activate Teads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25097035", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 563, "text": "TEADs on their own are unable to activate transcription and they require the help of coactivators. Several TEAD-interacting coactivators are known and they can be classified into three groups: (1) YAP and its paralog TAZ;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "YAP and TAZ are transcription coactivators and effectors of the Hippo pathway, which play a key role in organ size control. Through interaction with transcription factors such as TEADs, they activate gene transcription and thus promote cell proliferation, inhibit apoptosis, and regulate cell differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23985334", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 679, "text": "The YAP/TAZ-TEAD complex also upregulates several other proliferation-promoting genes and also promotes anchorage-independent cell proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22632831", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 973, "text": "hree-dimensional structure of the YAP-TEAD complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439427", "endSection": "abstract" } ] }, { "body": "How many genes outside of the MHC locus have been genetically associated to Rheumatoid Arthritis through GWAS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21542789", "http://www.ncbi.nlm.nih.gov/pubmed/23251581", "http://www.ncbi.nlm.nih.gov/pubmed/20453842", "http://www.ncbi.nlm.nih.gov/pubmed/23251214", "http://www.ncbi.nlm.nih.gov/pubmed/23288628", "http://www.ncbi.nlm.nih.gov/pubmed/18082339", "http://www.ncbi.nlm.nih.gov/pubmed/21427575", "http://www.ncbi.nlm.nih.gov/pubmed/16000323", "http://www.ncbi.nlm.nih.gov/pubmed/23381558", "http://www.ncbi.nlm.nih.gov/pubmed/23574521", "http://www.ncbi.nlm.nih.gov/pubmed/19772830", "http://www.ncbi.nlm.nih.gov/pubmed/21383967" ], "ideal_answer": [ "Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. To date, over 30 non-MHC RA-associated loci have been identified in humans, and over 100 arthritis-associated loci have been identified in rodent models of RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases." ], "exact_answer": [ "more than 30" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001171", "http://www.disease-ontology.org/api/metadata/DOID:676", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056426", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005258", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055106" ], "type": "factoid", "id": "531af8cbb166e2b80600003a", "snippets": [ { "offsetInBeginSection": 275, "offsetInEndSection": 601, "text": "Genome-Wide Association Studies (GWAS) have allowed the characterization of more than 40 new susceptibility genes and the confirmation of a marked differential genetic background between patients expressing anti-cyclic citrullinated peptide antibodies (ACPA, approximately 80% of all RA patients) and ACPA negative RA patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574521", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 401, "text": "Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23381558", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 986, "text": "The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288628", "endSection": "abstract" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1099, "text": "The meta-analysis results showed that: (1) 30, 28 and 26 SNPs were significantly associated with RA (P<0.01) for the allele, dominant, and recessive models, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23251581", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 572, "text": "This paper compares corresponding non-MHC genomic regions identified in rodent and human genome-wide association studies (GWAS). To date, over 30 non-MHC RA-associated loci have been identified in humans, and over 100 arthritis-associated loci have been identified in rodent models of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23251214", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 512, "text": "Interestingly, a series of candidate genes have been identified outside of the classical major histocompatibility (MHC) locus, which had long been regarded as the major contributor to the pathogenesis of this disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542789", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 626, "text": "Among these genes, PTPN22 plays an outstanding role. CD40, STAT4, PRM1, and TNFAIP3 also seem to be of relevance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542789", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 485, "text": "Genome-wide association studies (GWASs) added about 10 new loci to the list of already more than 20 loci associated with RA, so the list is now over 30", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21427575", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 346, "text": "Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21383967", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 900, "text": "These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20453842", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1074, "text": "An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20453842", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 350, "text": "Genome-wide association studies have expanded the number of validated RA risk loci beyond HLA-DRB1 \"shared epitope\" alleles to include additional major histocompatibility complex (MHC) risk alleles and more than 10 regions outside the MHC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19772830", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 665, "text": "We successfully identified 41 significant SNPs relevant to RA, 25 associated genes and a number of important SNP-SNP interactions (SNP patterns)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18082339", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 960, "text": "A total of 47 candidate regions were identified. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16000323", "endSection": "abstract" } ] }, { "body": "Are optogenetics tools used in the study and treatment of epilepsy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24491965", "http://www.ncbi.nlm.nih.gov/pubmed/25108607", "http://www.ncbi.nlm.nih.gov/pubmed/24005292", "http://www.ncbi.nlm.nih.gov/pubmed/19581573", "http://www.ncbi.nlm.nih.gov/pubmed/24965021", "http://www.ncbi.nlm.nih.gov/pubmed/25303540", "http://www.ncbi.nlm.nih.gov/pubmed/25678887", "http://www.ncbi.nlm.nih.gov/pubmed/23340416", "http://www.ncbi.nlm.nih.gov/pubmed/25012388", "http://www.ncbi.nlm.nih.gov/pubmed/22698957", "http://www.ncbi.nlm.nih.gov/pubmed/23871610", "http://www.ncbi.nlm.nih.gov/pubmed/25710834", "http://www.ncbi.nlm.nih.gov/pubmed/23637949", "http://www.ncbi.nlm.nih.gov/pubmed/25451697", "http://www.ncbi.nlm.nih.gov/pubmed/24573293", "http://www.ncbi.nlm.nih.gov/pubmed/23143518", "http://www.ncbi.nlm.nih.gov/pubmed/22890709", "http://www.ncbi.nlm.nih.gov/pubmed/24590406", "http://www.ncbi.nlm.nih.gov/pubmed/23406911" ], "ideal_answer": [ "Using optogenetics tools it is possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004827", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062308" ], "type": "yesno", "id": "56e0797451531f7e3300000f", "snippets": [ { "offsetInBeginSection": 246, "offsetInEndSection": 596, "text": "The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23637949", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 267, "text": "This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012388", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 946, "text": "We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24573293", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 1019, "text": " Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24573293", "endSection": "abstract" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 1762, "text": "Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24573293", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1383, "text": "Recently, a number of experiments have explored the treatments for epilepsy with optogenetic control of neurons. Here, we discuss the possibility that an optogenetic approach could be used to control the release of gliotransmitters and improve astrocyte function such as glutamate and K(+) uptake, and thereby offer a potential strategy to investigate and treat astrocyte-related epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451697", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 637, "text": "Optogenetic and designer receptor technologies provide unprecedented and much needed specificity, allowing for spatial, temporal and cell type-selective modulation of neuronal circuits. Using such tools, it is now possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25710834", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1121, "text": "We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012388", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 819, "text": "Moreover, optogenetics may be considered for developing potential treatment strategies for brain diseases, particularly for excitability disorders such as epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22698957", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 403, "text": "This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "How might novel technologies such as optogenetics lead to better treatments in epilepsy?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012388", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "WONOEP appraisal: optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303540", "endSection": "title" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1675, "text": "Finally, optogenetic tools allow rapid and reversible suppression of epileptic electroencephalography (EEG) activity upon photoactivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303540", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1356, "text": "Our data suggest that epileptiform activity in the hippocampus caused by impaired inhibition may be controlled by optogenetic silencing of principal neurons and potentially can be developed as an alternative treatment for epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24491965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Seizure suppression by high frequency optogenetic stimulation using in vitro and in vivo animal models of epilepsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108607", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24573293", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 947, "text": "We first discuss the benefits and caveats to using optogenetic approaches and recent advances in optogenetics related tools. We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012388", "endSection": "abstract" } ] }, { "body": "In which phase of cell cycle does stress-induced transcription-associated mutagenesis (TAM) occur?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16950921", "http://www.ncbi.nlm.nih.gov/pubmed/22201950", "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "http://www.ncbi.nlm.nih.gov/pubmed/20479947", "http://www.ncbi.nlm.nih.gov/pubmed/20036541" ], "ideal_answer": [ "Factors involved in RNA polymerase (RNAP) processivity or transcriptional derepression, such as Mfd (transcription coupling repair factor), contribute to the generation of stress-induced mutations. Under stress, transcription-associated mutagenesis is increased. Stress-induced transcription-associated mutations are acquired by nondividing cells, during stationary phase, and are not observed under conditions of exponential growth." ], "exact_answer": [ "stationary phase" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007049", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006351", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000115", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0022403", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090418" ], "type": "factoid", "id": "5544de7a5beec11c10000005", "snippets": [ { "offsetInBeginSection": 716, "offsetInEndSection": 1152, "text": "factors involved in RNA polymerase (RNAP) processivity or transcriptional derepression contribute to the generation of stress-induced mutations. In Bacillus subtilis, transcription-associated mutagenesis has been shown to be independent of recombination-dependent repair and, in some cases, of the Y DNA polymerases. Central to stationary-phase mutagenesis in B. subtilis is the requirement for Mfd, transcription coupling repair factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22201950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Adaptive (stationary phase) mutagenesis is a phenomenon by which nondividing cells acquire beneficial mutations as a response to stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 1205, "text": "the level of Leu(+) reversions increased significantly in parallel with the induced increase in transcription levels. This mutagenic response was not observed under conditions of exponential growth. Since transcription is a ubiquitous biological process, transcription-associated mutagenesis may influence evolutionary processes in all organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Transcription-associated mutation in Bacillus subtilis cells under stress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "endSection": "title" }, { "offsetInBeginSection": 320, "offsetInEndSection": 415, "text": "Transcription-associated mutagenesis is increased under stress and depends on the DNA sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479947", "endSection": "abstract" }, { "offsetInBeginSection": 1934, "offsetInEndSection": 2028, "text": "Nonrandom transcription-associated mutagenesis under stress should improve the survival of E.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479947", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 400, "text": "Transcription-associated mutagenesis is increased under stress and depends on the DNA sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20479947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Stress-induced mutagenesis describes the accumulation of mutations that occur in nongrowing cells, in contrast to mutagenesis that occurs in actively dividing populations, and has been referred to as stationary-phase or adaptive mutagenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20036541", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1077, "text": "Central to stationary-phase mutagenesis in B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22201950", "endSection": "abstract" } ] }, { "body": "Which proteins are related to the loss of cell-cell adhesion during EMT (epithelial-mesenchymal transition)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "http://www.ncbi.nlm.nih.gov/pubmed/16080193", "http://www.ncbi.nlm.nih.gov/pubmed/19604397", "http://www.ncbi.nlm.nih.gov/pubmed/19029937", "http://www.ncbi.nlm.nih.gov/pubmed/20168079", "http://www.ncbi.nlm.nih.gov/pubmed/23880940", "http://www.ncbi.nlm.nih.gov/pubmed/18611248", "http://www.ncbi.nlm.nih.gov/pubmed/22249256" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/go/0001837", "o": "http://purl.uniprot.org/go/0014031" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0014031", "o": "http://www.geneontology.org/go#GO:0014031" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0001837", "o": "EMT" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0001837", "o": "epithelial-mesenchymal transition" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0001837", "o": "http://www.geneontology.org/go#GO:0001837" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0014031", "o": "mesenchymal cell development" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0001837", "o": "epithelial to mesenchymal transition" } ], "ideal_answer": [ "Transcriptional and post-transcriptional regulatory mechanisms mediated by several inducers of EMT, in particular the ZEB and Snail factors, downregulate the expression and/or functional organization of core polarity complexes. Functional loss of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration during embryonic development and tumour invasion. Recently, we found that aPKC can also phosphorylate Par6 to drive EMT and increase the migratory potential of non-small cell lung cancer cells. We propose that the regulation of EMT by SIRT1 involves modulation of, and cooperation with, the EMT inducing transcription factor ZEB1. Knockdown of Numb by shRNA in MDCK cells led to a lateral to apical translocation of E-cadherin and beta-catenin, active F-actin polymerization, mis-localization of Par3 and aPKC, a decrease in cell-cell adhesion and an increase in cell migration and proliferation. Growth factors such as TGFb and EGF have also been shown to be related to EMT." ], "exact_answer": [ [ "ZEB" ], [ "SNAIL" ], [ "SIRT1" ], [ "EGF" ], [ "TGFb" ], [ "aPKC" ], [ "Par6" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4269222", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002448", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007155", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058750" ], "type": "list", "id": "531b3ff3b166e2b80600003d", "snippets": [ { "offsetInBeginSection": 4, "offsetInEndSection": 82, "text": "conserved polarity proteins Par6 and aPKC regulate cell polarization processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880940", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 643, "text": " In addition to signaling pathways that alter genetic programes that trigger the loss of cell-cell adhesion, alternative pathways can alter cell plasticity to regulate cell-cell cohesion and increase invasive potential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880940", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 707, "text": "One such pathway involves TGF\u03b2-induced phosphorylation of Par6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880940", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1007, "text": "Recently, we found that aPKC can also phosphorylate Par6 to drive EMT and increase the migratory potential of non-small cell lung cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880940", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 493, "text": "Here, we propose a novel mechanism through which the nicotinamide adenine dinucleotide-dependent histone deacetylase SIRT1 regulates EMT in prostate cancer cells through cooperation with the EMT inducing transcription factor ZEB1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249256", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 993, "text": "In contrast, silencing SIRT1 in metastatic prostate tumor cells restores cell-cell adhesion and induces a shift toward an epithelial morphology concomitant with increased expression of E-cadherin and decreased expression of mesenchymal markers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249256", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1123, "text": "We also found that SIRT1 has a physiologically relevant role in endogenous EMT induced by EGF signaling in prostate cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249256", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1260, "text": "We propose that the regulation of EMT by SIRT1 involves modulation of, and cooperation with, the EMT inducing transcription factor ZEB1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249256", "endSection": "abstract" }, { "offsetInBeginSection": 1523, "offsetInEndSection": 1587, "text": "We thus identify a necessary role for ZEB1 in SIRT1-mediated EMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249256", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 305, "text": "Numb has been shown to play an important role in the proper functions of Par protein complex and in cell-cell junctions, both of which are associated with EMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20168079", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 450, "text": "Recently, we showed that Numb is capable of binding to both Par3 and E-cadherin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20168079", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 873, "text": "Knockdown of Numb by shRNA in MDCK cells led to a lateral to apical translocation of E-cadherin and beta-catenin, active F-actin polymerization, mis-localization of Par3 and aPKC, a decrease in cell-cell adhesion and an increase in cell migration and proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20168079", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 328, "text": "This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/deltaEF1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19604397", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 770, "text": "EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19604397", "endSection": "abstract" }, { "offsetInBeginSection": 2071, "offsetInEndSection": 2271, "text": "ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/deltaEF1 induction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19604397", "endSection": "abstract" }, { "offsetInBeginSection": 2273, "offsetInEndSection": 2392, "text": "This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19604397", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 214, "text": "unctional loss of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration during embryonic development and tumour invasion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 939, "text": "Transcriptional and post-transcriptional regulatory mechanisms mediated by several inducers of EMT, in particular the ZEB and Snail factors, downregulate the expression and/or functional organization of core polarity complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19029937", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 170, "text": "TGFbeta has pleiotropic effects that range from regulation of proliferation and apoptosis to morphological changes and epithelial-mesenchymal transition (EMT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18611248", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1380, "text": "Morphological changes were accompanied by decrease in E-cadherin and increased Snail expression but the mesenchymal markers (N-cadherin, SMAalpha and Vimentin) studied remained unchanged", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18611248", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 794, "text": "Neutralising E-cadherin function promoted the invasion and inhibited the aggregation of endocrine-sensitive MCF7 cells, whilst having little effect on the behaviour of TamR cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16080193", "endSection": "abstract" } ] }, { "body": "Is micro RNA 1 (miR-1) implicated in cardiac arrhythmias?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19959133", "http://www.ncbi.nlm.nih.gov/pubmed/20015039", "http://www.ncbi.nlm.nih.gov/pubmed/17401374", "http://www.ncbi.nlm.nih.gov/pubmed/22045061", "http://www.ncbi.nlm.nih.gov/pubmed/19581315", "http://www.ncbi.nlm.nih.gov/pubmed/19933931", "http://www.ncbi.nlm.nih.gov/pubmed/23678295", "http://www.ncbi.nlm.nih.gov/pubmed/20163779", "http://www.ncbi.nlm.nih.gov/pubmed/19131648", "http://www.ncbi.nlm.nih.gov/pubmed/19519553", "http://www.ncbi.nlm.nih.gov/pubmed/23922949" ], "ideal_answer": [ "Yes. miR-1 overexpression may contribute to the increased susceptibility of the heart to AVB, which provides us novel insights into the molecular mechanisms underlying ischemic cardiac arrhythmias. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients.", "Yes, changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure. it has been shown that miR-1 over-expression in normal or infarcted rat hearts exacerbates arrhythmogenesis, while elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001145" ], "type": "yesno", "id": "54f4627e64850a5854000007", "snippets": [ { "offsetInBeginSection": 115, "offsetInEndSection": 274, "text": "Dysfunction of the gap junction protein connexin 43 (Cx43), an established miR-1 target, during cardiac hypertrophy leads to ventricular tachyarrhythmias (VT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23922949", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1475, "text": "miR-1 overexpression may contribute to the increased susceptibility of the heart to AVB, which provides us novel insights into the molecular mechanisms underlying ischemic cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23678295", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 733, "text": "The incidence of AVB was higher in miR-1 Tg mice than that in wild-type (WT) mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23678295", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1230, "text": "As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20163779", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 747, "text": "Lately, some highlight articles revealed that the altered expression of miRNAs such as miR-1, miR-133, miR-21, miR-208 etc in hearts also contributed to cardiovascular diseases, such as heart ischemia, cardiac hypertrophy, and arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20015039", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 450, "text": "MicroRNA-1 (miR-1) reciprocally regulates inwardly rectifying potassium channel (Kir)2.1 expression in coronary disease, contributing to arrhythmogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19959133", "endSection": "abstract" }, { "offsetInBeginSection": 1575, "offsetInEndSection": 1909, "text": "miR-1 levels are greatly reduced in human AF, possibly contributing to up-regulation of Kir2.1 subunits, leading to increased I(K1). Because up-regulation of inward-rectifier currents is important for AF maintenance, these results provide potential new insights into molecular mechanisms of AF with potential therapeutic implications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19959133", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 397, "text": "The muscle-specific miR-1 has been implicated in cardiac hypertrophy, heart development, cardiac stem cell differentiation, and arrhythmias through targeting of regulatory proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933931", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1478, "text": "We conclude that the beta-adrenergic pathway can stimulate expression of arrhythmogenic miR-1, contributing to ischaemic arrhythmogenesis, and beta-blockers produce their beneficial effects partially by down-regulating miR-1, which might be a novel strategy for ischaemic cardioprotection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19581315", "endSection": "abstract" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1152, "text": "MiR-1 influences susceptibility to cardiac arrhythmias after myocardial infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19519553", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 287, "text": "Changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19131648", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1221, "text": "In the presence of isoproterenol, rhythmically paced, miR-1-overexpressing myocytes exhibited spontaneous arrhythmogenic oscillations of intracellular Ca(2+), events that occurred rarely in control myocytes under the same conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19131648", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 889, "text": "Here we show that miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. Elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17401374", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1290, "text": " Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17401374", "endSection": "abstract" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1151, "text": "MiR-1 influences susceptibility to cardiac arrhythmias after myocardial infarction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19519553", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 383, "text": "The muscle-specific miR-1 has been implicated in cardiac hypertrophy, heart development, cardiac stem cell differentiation, and arrhythmias through targeting of regulatory proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933931", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 286, "text": "Changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19131648", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 255, "text": "Changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22045061", "endSection": "abstract" } ] }, { "body": "Are there Conserved Noncoding Elements (CNEs) in invertebrate genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24282393", "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "http://www.ncbi.nlm.nih.gov/pubmed/17274809", "http://www.ncbi.nlm.nih.gov/pubmed/23357263", "http://www.ncbi.nlm.nih.gov/pubmed/18402933" ], "ideal_answer": [ "Yes.", "Yes. Conserved Noncoding Elements (CNEs) have also been found in invertebrate genomes." ], "exact_answer": "yes", "type": "yesno", "id": "553a6a9fbc4f83e82800001c", "snippets": [ { "offsetInBeginSection": 451, "offsetInEndSection": 708, "text": "Here, we use genome-wide comparisons between C. intestinalis and C. savignyi to identify putative urochordate cis-regulatory sequences. Ciona conserved non-coding elements (ciCNEs) are associated with largely the same key regulatory genes as vertebrate CNEs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "We have identified Conserved Non-coding Elements (CNEs) in the regulatory region of Caenorhabditis elegans and Caenorhabditis briggsae ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18402933", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 781, "text": "Here we report that nematode genomes contain an alternative set of CNEs that share sequence characteristics, but not identity, with their vertebrate counterparts. CNEs thus represent a very unusual class of sequences that are extremely conserved within specific animal lineages yet are highly divergent between lineages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17274809", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1280, "text": "A core set of genes that regulate development is associated with CNEs across three animal groups (worms, flies and vertebrates)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17274809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "endSection": "abstract" } ] }, { "body": "Which tumor suppressor is referred to as \"the guardian of the genome\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17589818", "http://www.ncbi.nlm.nih.gov/pubmed/21875573", "http://www.ncbi.nlm.nih.gov/pubmed/22017796", "http://www.ncbi.nlm.nih.gov/pubmed/19243304", "http://www.ncbi.nlm.nih.gov/pubmed/11156366", "http://www.ncbi.nlm.nih.gov/pubmed/24264057", "http://www.ncbi.nlm.nih.gov/pubmed/20165689", "http://www.ncbi.nlm.nih.gov/pubmed/25302307", "http://www.ncbi.nlm.nih.gov/pubmed/22248668", "http://www.ncbi.nlm.nih.gov/pubmed/11729185", "http://www.ncbi.nlm.nih.gov/pubmed/20406950", "http://www.ncbi.nlm.nih.gov/pubmed/23103206", "http://www.ncbi.nlm.nih.gov/pubmed/22528751", "http://www.ncbi.nlm.nih.gov/pubmed/23209608", "http://www.ncbi.nlm.nih.gov/pubmed/19128788", "http://www.ncbi.nlm.nih.gov/pubmed/18336191", "http://www.ncbi.nlm.nih.gov/pubmed/22978174", "http://www.ncbi.nlm.nih.gov/pubmed/18794879", "http://www.ncbi.nlm.nih.gov/pubmed/24231949", "http://www.ncbi.nlm.nih.gov/pubmed/23948487", "http://www.ncbi.nlm.nih.gov/pubmed/22611192", "http://www.ncbi.nlm.nih.gov/pubmed/12629332", "http://www.ncbi.nlm.nih.gov/pubmed/15701641", "http://www.ncbi.nlm.nih.gov/pubmed/23412905", "http://www.ncbi.nlm.nih.gov/pubmed/20935678", "http://www.ncbi.nlm.nih.gov/pubmed/12494467", "http://www.ncbi.nlm.nih.gov/pubmed/21341346", "http://www.ncbi.nlm.nih.gov/pubmed/20740625", "http://www.ncbi.nlm.nih.gov/pubmed/22374721", "http://www.ncbi.nlm.nih.gov/pubmed/11906841", "http://www.ncbi.nlm.nih.gov/pubmed/19184427", "http://www.ncbi.nlm.nih.gov/pubmed/17457049", "http://www.ncbi.nlm.nih.gov/pubmed/21452930", "http://www.ncbi.nlm.nih.gov/pubmed/8844397", "http://www.ncbi.nlm.nih.gov/pubmed/9219832", "http://www.ncbi.nlm.nih.gov/pubmed/15033688", "http://www.ncbi.nlm.nih.gov/pubmed/20922462" ], "ideal_answer": [ "The major tumour suppressor protein, p53, is one of the most well-studied proteins in cell biology. It plays a crucial role in regulating the transcription of numerous genes responsible for cells cycle arrest, DNA repair, angiogenesis, cell senescence, or apoptosis in response to various stress signals, and is considered one of the most important players in the development of cancer. p53 contributes to the maintenance of genomic stability. Thus, p53 has been described as \"the guardian of the genome\"." ], "exact_answer": [ "p53" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051726", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016147", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025521" ], "type": "factoid", "id": "55421ee7ccca0ce74b000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "The major tumour suppressor protein, p53, is one of the most well-studied proteins in cell biology. Often referred to as the Guardian of the Genome, the list of known functions of p53 include regulatory roles in cell cycle arrest, apoptosis, angiogenesis, DNA repair and cell senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24264057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "p53-Based cyclotherapy: exploiting the 'guardian of the genome' to protect normal cells from cytotoxic therapy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231949", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "The tumor suppressor protein p53 has been described \"as the guardian of the genome\" for its crucial role in regulating the transcription of numerous genes responsible for cells cycle arrest, senescence, or apoptosis in response to various stress signals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23209608", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 929, "text": "the critical tumor suppressor p53, known as the guardian of the genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22528751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "p53 is well known as the \"guardian of the genome\" for differentiated and neoplastic cells. p53 induces cell-cycle arrest and cell death after DNA damage and thus contributes to the maintenance of genomic stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22248668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "The classical functions of p53 protein are those related to its role on DNA damage, cell growth arrest, senescence and apoptosis. For this reason it is called 'the guardian of the genome' and is considered one of the most important players in the development of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21452930", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 375, "text": "Tumor suppressor p53 is a genome guardian and important negative regulator of the cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22611192", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 601, "text": "The p53 gene is a tumor suppressor gene that acts as \"guardian of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12629332", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 394, "text": "Among many genetic lesions, mutational inactivation of p53 tumor suppressor, the \"guardian of the genome,\" is the most frequent event found in 50% of human cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20165689", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1147, "text": "The tumor suppressor p53 is known as a guardian of the genome that mediates the cellular response to environmental stress, leading to cell cycle arrest or cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18794879", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1234, "text": "This is the first report that demonstrates the mechanism of action of the MAR-binding protein SMAR1 in modulating the activity of p53, often referred to as the \"guardian of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17589818", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The tumor suppressor p53 is often referred to as \"the guardian of the genome\" because of its central role in the cellular response to oncogenic stress and prevention of tumor development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20406950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The tumor suppressor p53, encoded by the TP53 gene, is recognized as the guardian of the human genome because it regulates many downstream genes to exercise its function in cell cycle and cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20935678", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 296, "text": "p53, the guardian of the genome, is the most important tumor suppressor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23948487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The tumor suppressor protein p53 is often referred to as the guardian of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23103206", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 462, "text": "The tumor suppressor p53 is the most frequently mutated gene in human cancer and is often referred to as the \"guardian of the genome\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875573", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 396, "text": "The p53 tumor suppressor protein is often referred to as the \"guardian of the genome\" since its response to DNA-damage or checkpoint failure gives rise to a series of anti-proliferative responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18336191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Tumor suppressor p53, known as the guardian of the genome, has the ability to prevent the emergence of transformed cells by the induction of cell cycle arrest and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22978174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Tumor suppressor p53 functions as a \"guardian of the genome\" to prevent cells from transformation. p53 is constitutively ubiquitinated and degradated in unstressed conditions, thereby suppressing the expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374721", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 244, "text": "Commonly referred as a \"guardian of the genome\", p53 is responsible for determining the fate of the cell when the integrity of its genome is damaged.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21341346", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 212, "text": "The p53 gene is involved in genome stability and thus is referred to as \"the guardian of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20740625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "p53 has been referred to as the guardian of the genome because of its role in protecting the cell from DNA damage. p53 performs its duties by regulating cell-cycle progression and DNA repair and, in cases of irreparable DNA damage, by executing programmed cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19243304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The p53 gene has been referred to as the guardian of the genome because it controls apoptosis and cell cycle arrest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19184427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The tumor suppressor protein, p53, is often referred to as the guardian of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11906841", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 463, "text": "The tumor suppressor p53 is the most frequently mutated gene in human cancer and is often referred to as the \"guardian of the genome\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11156366", "endSection": "title" }, { "offsetInBeginSection": 96, "offsetInEndSection": 245, "text": "Commonly referred as a \"guardian of the genome\", p53 is responsible for determining the fate of the cell when the integrity of its genome is damaged.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21341346", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1154, "text": "The tumor suppressor p53 is known as a guardian of the genome that mediates the cellular response to environmental stress, leading to cell cycle arrest or cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18794879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "p53, sometimes referred to as the \"guardian of the genome,\" helps regulate cell-cycle arrest, DNA-damage repair, apoptosis, and senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19128788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "The tumor suppressor protein p53 is often referred to as the guardian of the genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23103206", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 395, "text": "The p53 tumor suppressor protein is often referred to as the \"guardian of the genome\" since its response to DNA-damage or checkpoint failure gives rise to a series of anti-proliferative responses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18336191", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 462, "text": "The tumor suppressor p53 is the most frequently mutated gene in human cancer and is often referred to as the \"guardian of the genome\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875573", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 710, "text": "Remarkably, the guardians--p53, p73, and p63--of the genome are in control of most of the known tumor suppressor miRNAs, tumor suppressor genes, and metastasis suppressors by suppressing c-myc through miR-145/let-7/miR-34/TRIM32/PTEN/FBXW7", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20922462", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 413, "text": "The p53 gene is involved in genome stability and thus is referred to as \"the guardian of the genome.\" To better understand the antigenotoxic effects of p53 in ultraviolet light B (UVB)-induced mutagenesis, mutations were measured in the epidermis of UVB-irradiated p53(+/+) and p53(-/-) gpt delta mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20740625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The guardians of the genome (p53, TA-p73, and TA-p63) are regulators of tumor suppressor miRNAs network.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20922462", "endSection": "title" }, { "offsetInBeginSection": 624, "offsetInEndSection": 763, "text": "Therefore, while p53 can be rightly defined as the guardian of the genome, we could think of p73 as the \"assistant\" guardian of the genome!", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15033688", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1153, "text": "The tumor suppressor p53 is known as a guardian of the genome that mediates the cellular response to environmental stress, leading to cell cycle arrest or cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18794879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The tumor suppressor protein, p53, is often referred to as the guardian of the genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11906841", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1242, "text": "This is the first report that demonstrates the mechanism of action of the MAR-binding protein SMAR1 in modulating the activity of p53, often referred to as the \"guardian of the genome.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701641", "endSection": "abstract" } ] }, { "body": "What is known about diseases associated with mutations in the CHCHD10 gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24934289", "http://www.ncbi.nlm.nih.gov/pubmed/25428574", "http://www.ncbi.nlm.nih.gov/pubmed/25193783", "http://www.ncbi.nlm.nih.gov/pubmed/25155093" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "D004194" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0015570", "o": "D004194" } ], "ideal_answer": [ "Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. \nMutations in the CHCHD10 gene have been identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment.\nOther findings links CHCHD10 mutations to mitochondrial myopathy.", "Mutations in the CHCHD10 gene have been recently identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057180", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.disease-ontology.org/api/metadata/DOID:332", "http://www.disease-ontology.org/api/metadata/DOID:9255", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000690" ], "type": "summary", "id": "5717e0717de986d80d000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Late onset spinal motor neuronopathy is caused by mutation in CHCHD10.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25428574", "endSection": "title" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1249, "text": "Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. During the preparation of this article other mutations were reported to cause frontotemporal dementia-amyotrophic lateral sclerosis syndrome, indicating that the CHCHD10 gene is largely important for the motor and cognitive neuronal systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25428574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25193783", "endSection": "title" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1599, "text": "Our findings identify a novel gene causing mitochondrial myopathy, thereby expanding the spectrum of mitochondrial myopathies caused by nuclear genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25193783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Mutations in the CHCHD10 gene have been recently identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1783, "text": "The observation of a frontotemporal dementia-amyotrophic lateral sclerosis phenotype in a mitochondrial disease led us to analyse CHCHD10 in a cohort of 21 families with pathologically proven frontotemporal dementia-amyotrophic lateral sclerosis. We identified the same missense p.Ser59Leu mutation in one of these families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24934289", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 841, "text": "This study demonstrates the implication of CHCHD10 in FTD and ALS spectrum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 511, "text": "However, the exact contribution of CHCHD10 in FTD and ALS diseases spectrum remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 731, "text": "In this study, we evaluated the frequency of CHCHD10 mutations in 115 patients with FTD and FTD-ALS phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 1696, "offsetInEndSection": 1942, "text": "The observation of a frontotemporal dementia-amyotrophic lateral sclerosis phenotype in a mitochondrial disease led us to analyse CHCHD10 in a cohort of 21 families with pathologically proven frontotemporal dementia-amyotrophic lateral sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24934289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Screening of CHCHD10 in a French cohort confirms the involvement of this gene in frontotemporal dementia with amyotrophic lateral sclerosis patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24934289", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Mutations in the CHCHD10 gene have been recently identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1008, "text": "The mutation was shown to segregate with the disease in 55 patients from 17 families.INTERPRETATION: Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25428574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Mutations in the CHCHD10 gene have been recently identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 512, "text": "However, the exact contribution of CHCHD10 in FTD and ALS diseases spectrum remains unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1705, "text": "The observation of a frontotemporal dementia-amyotrophic lateral sclerosis phenotype in a mitochondrial disease led us to analyse CHCHD10 in a cohort of 21 families with pathologically proven frontotemporal dementia-amyotrophic lateral sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24934289", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 842, "text": "This study demonstrates the implication of CHCHD10 in FTD and ALS spectrum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Mutations in the CHCHD10 gene have been recently identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25155093", "endSection": "abstract" } ] }, { "body": "Which drug should be used as an antidote in benzodiazepine overdose?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1354979", "http://www.ncbi.nlm.nih.gov/pubmed/7629986", "http://www.ncbi.nlm.nih.gov/pubmed/8438687", "http://www.ncbi.nlm.nih.gov/pubmed/2893240", "http://www.ncbi.nlm.nih.gov/pubmed/11349753", "http://www.ncbi.nlm.nih.gov/pubmed/18175099", "http://www.ncbi.nlm.nih.gov/pubmed/14620397", "http://www.ncbi.nlm.nih.gov/pubmed/9306053", "http://www.ncbi.nlm.nih.gov/pubmed/8644960", "http://www.ncbi.nlm.nih.gov/pubmed/1672103", "http://www.ncbi.nlm.nih.gov/pubmed/8239101", "http://www.ncbi.nlm.nih.gov/pubmed/2113543", "http://www.ncbi.nlm.nih.gov/pubmed/1996802", "http://www.ncbi.nlm.nih.gov/pubmed/8905360", "http://www.ncbi.nlm.nih.gov/pubmed/21785147", "http://www.ncbi.nlm.nih.gov/pubmed/1286503", "http://www.ncbi.nlm.nih.gov/pubmed/2575692", "http://www.ncbi.nlm.nih.gov/pubmed/19500521", "http://www.ncbi.nlm.nih.gov/pubmed/8605789", "http://www.ncbi.nlm.nih.gov/pubmed/8306565", "http://www.ncbi.nlm.nih.gov/pubmed/11383664", "http://www.ncbi.nlm.nih.gov/pubmed/3132054", "http://www.ncbi.nlm.nih.gov/pubmed/2231833", "http://www.ncbi.nlm.nih.gov/pubmed/2899985" ], "ideal_answer": [ "Flumazenil should be used in all patients presenting with suspected benzodiazepine overdose. Flumazenil is a potent benzodiazepine receptor antagonist that competitively blocks the central effects of benzodiazepines and reverses behavioral, neurologic, and electrophysiologic effects of benzodiazepine overdose. Clinical efficacy and safety of flumazenil in treatment of benzodiazepine overdose has been confirmed in a number of rigorous clinical trials. In addition, flumazenil is also useful to to reverse benzodiazepine induced sedation and to and to diagnose benzodiazepine overdose." ], "exact_answer": [ "flumazenil" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062787", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001569", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000931" ], "type": "factoid", "id": "514a0a57d24251bc05000051", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 250, "text": "Benzodiazepine (BZD) overdose (OD) continues to cause significant morbidity and mortality in the UK. Flumazenil is an effective antidote but there is a risk of seizures, particularly in those who have co-ingested tricyclic antidepressants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21785147", "endSection": "sections.0" }, { "offsetInBeginSection": 530, "offsetInEndSection": 698, "text": "Flumazenil was administered to 80 patients in 4504 BZD-related enquiries, 68 of whom did not have ventilatory failure or had recognised contraindications to flumazenil.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21785147", "endSection": "sections.0" }, { "offsetInBeginSection": 1366, "offsetInEndSection": 1436, "text": "Flumazenil is used infrequently in the management of BZD OD in the UK.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21785147", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Flumazenil is a benzodiazepine antagonist. It is widely used as an antidote in comatose patients suspected of having ingested a benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19500521", "endSection": "sections.0" }, { "offsetInBeginSection": 2100, "offsetInEndSection": 2227, "text": "Flumazenil is very useful in reversing benzodiazepine-induced sedation as well as to diagnose or treat benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18175099", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Flumazenil is indicated for reversal of sedation from benzodiazepines administered during therapeutic or diagnostic procedures and during induction or maintenance of general anesthesia, as well as for benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14620397", "endSection": "sections.0" }, { "offsetInBeginSection": 766, "offsetInEndSection": 990, "text": "When measures are required to ensure adequate recovery of a patient's respiratory function and mental awareness, such as in patients with benzodiazepine toxicity, consideration of continuous-infusion flumazenil is warranted.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14620397", "endSection": "sections.0" }, { "offsetInBeginSection": 439, "offsetInEndSection": 695, "text": "Flumazenil is a potent benzodiazepine antagonist that competitively blocks the central effects of benzodiazepines. It can reverse the sedative effects of benzodiazepines occurring after diagnostic or therapeutic procedures or after benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11349753", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "A 54-y-old man ingested 2 g of bulk laboratory diazepam and was treated with activated charcoal, enhanced diuresis and flumazenil infusion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11383664", "endSection": "sections.0" }, { "offsetInBeginSection": 200, "offsetInEndSection": 390, "text": "Flumazenil is a specific and competitive antagonist at the central benzodiazepine receptor, reversing all effects of benzodiazepine agonists without tranquillising or anticonvulsant actions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9306053", "endSection": "sections.0" }, { "offsetInBeginSection": 391, "offsetInEndSection": 676, "text": "Incremental intravenous bolus injections of flumazenil 0.1 to 0.3 mg are the most effective and well tolerated in the diagnosis and treatment of pure benzodiazepine overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9306053", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 277, "text": "Flumazenil is a competitive benzodiazepine antagonist that acts to reverse their sedative and hypnotic effects. It is indicated in the management of benzodiazepine overdose, but its role in the routine reversal of endoscopic conscious sedation has not been defined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8905360", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 119, "text": "To develop clinical rules for the safe and effective use of flumazenil in suspected benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8644960", "endSection": "sections.0" }, { "offsetInBeginSection": 438, "offsetInEndSection": 637, "text": "Unconscious patients (n = 110) suspected of benzodiazepine overdose, graded 2 to 4 on the Matthew and Lawson coma scale, were treated with flumazenil, the specific benzodiazepine receptor antagonist.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8605789", "endSection": "sections.0" }, { "offsetInBeginSection": 1685, "offsetInEndSection": 2084, "text": "Fourteen of 17 double-blind, flumazenil-treated patients woke after a mean of 0.8 +/- 0.3 (SD) mg vs. one of 14 placebo patients (p < .001). Seventy-five percent of the aggregated controlled and uncontrolled patients awoke from coma scores of 3.1 +/- 0.6 to 0.4 +/- 0.5 (p < .01) after the injection of 0.7 +/- 0.3 mg of flumazenil. These patients had high benzodiazepine serum blood concentrations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8605789", "endSection": "sections.0" }, { "offsetInBeginSection": 3379, "offsetInEndSection": 3459, "text": "Flumazenil is effective in preventing recurrence of benzodiazepine-induced coma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8605789", "endSection": "sections.0" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1550, "text": "Flumazenil is best left for reversal of therapeutic conscious sedation and rare select cases of benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7629986", "endSection": "sections.0" }, { "offsetInBeginSection": 161, "offsetInEndSection": 353, "text": "Flumazenil interacts at the central benzodiazepine receptor to antagonize or reverse the behavioral, neurologic, and electrophysiologic effects of benzodiazepine agonists and inverse agonists.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8306565", "endSection": "sections.0" }, { "offsetInBeginSection": 613, "offsetInEndSection": 862, "text": "It improves the level of consciousness in patients with benzodiazepine overdose; however, resedation may occur within one to two hours after administration, so repeated doses or a continuous infusion may be required to maintain therapeutic efficacy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8306565", "endSection": "sections.0" }, { "offsetInBeginSection": 1841, "offsetInEndSection": 2069, "text": "Flumazenil has been shown to reverse sedation caused by intoxication with benzodiazepines alone or benzodiazepines in combination with other agents, but it should not be used when cyclic antidepressant intoxication is suspected.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8306565", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Flumazenil, a specific benzodiazepine antagonist, was evaluated as adjunctive therapy in the management of benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1286503", "endSection": "sections.0" }, { "offsetInBeginSection": 831, "offsetInEndSection": 971, "text": "The mean CGIS score at 10 minutes for benzodiazepine-positive patients treated with flumazenil was 1.95 versus 3.58 for those given placebo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1286503", "endSection": "sections.0" }, { "offsetInBeginSection": 1346, "offsetInEndSection": 1539, "text": "Among the benzodiazepine-positive patients, 9 (53%) of 17 patients from the flumazenil group responded to the additional flumazenil, and 58 (81%) of patients previously given placebo responded.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1286503", "endSection": "sections.0" }, { "offsetInBeginSection": 2286, "offsetInEndSection": 2454, "text": "The results of this study confirm published reports of the efficacy of flumazenil in reversing benzodiazepine-induced sedation in patients with benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1286503", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Flumazenil, a specific benzodiazepine antagonist, is useful in reversing the sedation and respiratory depression that often occur when benzodiazepines are administered to patients undergoing anesthesia or when patients have taken an intentional benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8438687", "endSection": "sections.0" }, { "offsetInBeginSection": 2414, "offsetInEndSection": 2508, "text": "Flumazenil rapidly and effectively reverses the clinical signs and symptoms of a BDZ overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8239101", "endSection": "sections.0" }, { "offsetInBeginSection": 146, "offsetInEndSection": 288, "text": "Flumazenil is a benzodiazepine antagonist that is highly effective in reversing the central nervous system effects of benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1354979", "endSection": "sections.0" }, { "offsetInBeginSection": 645, "offsetInEndSection": 827, "text": "In the setting of isolated benzodiazepine overdose, flumazenil is capable of completely reversing coma within one to two minutes, with this effect lasting between one and five hours.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1996802", "endSection": "sections.0" }, { "offsetInBeginSection": 319, "offsetInEndSection": 682, "text": "Fifteen comatous patients with suspected sedatives/hypnotics overdose were included in this study and flumazenil 0.25 mg per dose was administrated intravenously. The average score of Glasgow Coma Scale increased from 7.13 +/- 2.92 to 10.93 +/- 3.67 after one dose of flumazenil. Clear consciousness was restored after multiple doses of flumazenil administration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1672103", "endSection": "sections.0" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1048, "text": "We concluded that flumazenil is an excellent antidote for benzodiazepine overdose and valuable for differentiating the patients in comatose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1672103", "endSection": "sections.0" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1307, "text": "Patients with benzodiazepine overdose who received 5 mg flumazenil regained consciousness about 1-2 min after the end of injection.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2231833", "endSection": "sections.0" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1485, "text": "We conclude that flumazenil is an effective and safe drug in the treatment of benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2113543", "endSection": "sections.0" }, { "offsetInBeginSection": 235, "offsetInEndSection": 380, "text": "Flumazenil is the first benzodiazepine antagonist which can be used in humans and is a well established for treatment of benzodiazepine overdose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2575692", "endSection": "sections.0" }, { "offsetInBeginSection": 420, "offsetInEndSection": 631, "text": "Flumazenil, a 1,4-imidazobenzodiazepine, is a highly effective, specific benzodiazepine antagonist which is indicated for use when the effect of a benzodiazepine must be attenuated or terminated at short notice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2893240", "endSection": "sections.0" }, { "offsetInBeginSection": 2200, "offsetInEndSection": 2509, "text": "Thus, flumazenil provides a safe and effective means of attenuating or reversing the CNS-depressant effects of benzodiazepines whenever indicated, e.g. following benzodiazepine-induced general anaesthesia, conscious sedation, or after benzodiazepine overdose, either alone or in combination with other agents.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2893240", "endSection": "sections.0" }, { "offsetInBeginSection": 3524, "offsetInEndSection": 3676, "text": "Flumazenil is safe when administered cautiously, even in patients with coma caused by a mixed overdose of benzodiazepine plus tricyclic antidepressants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8605789", "endSection": "sections.0" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1648, "text": "The mean +/- SD CGIS score at ten minutes for BDZ-positive patients was 1.41 +/- 0.72 for patients who received flumazenil and 3.41 +/- 0.91 for the placebo group (P < .01). There was no difference in the mean CGIS score between the flumazenil (3.25 +/- 1.15) and placebo (3.75 +/- 0.69) groups in BDZ-negative patients. The GCS and NAS were also significantly better in patients who were BDZ-positive and received flumazenil.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8239101", "endSection": "sections.0" }, { "offsetInBeginSection": 145, "offsetInEndSection": 665, "text": "In 23 patients admitted to the Intensive Care Unit with coma due to overdose with benzodiazepines or other sedatives, flumazenil i.v. (up to 2 mg or placebo) was given. In 13 patients given flumazenil the Glasgow Coma Scale (GCS) increased significantly from 4.9 to 7.8 (p less than 0.05). Six of these 13 patients, including mainly benzodiazepine mono-intoxications, needed only one series of injections (up to 1.0 mg flumazenil); the GCS increased thereby from 4.5 to 10.7 within a maximum of 5 min (p less than 0.01).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2113543", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "The efficacy and safety of flumazenil were assessed in comparison to placebo in a double-blind randomised study of 31 adults intoxicated with benzodiazepines. The criteria of efficacy were the degree of sedation, and orientation in time and space. Patients who received flumazenil awoke within minutes but central depression returned partly one hour later, which reflects the short elimination half-life of the drug.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3132054", "endSection": "sections.0" }, { "offsetInBeginSection": 417, "offsetInEndSection": 615, "text": "Side effects were few and the results indicate that flumazenil is effective in the primary management of benzodiazepine overdose and in states where benzodiazepines have been taken with other drugs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3132054", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Flumazenil (Ro 15-1788) proved to be a very efficacious competitive antagonist of benzodiazepines that reliably counteracts their pharmacological actions within 1-2 min as could be demonstrated in clinical and EEG studies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2899985", "endSection": "sections.0" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1411, "text": "In intensive care medicine, the antagonist may be used in the treatment of benzodiazepine overdose as well as in the differential diagnosis of a coma of unknown origin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2899985", "endSection": "sections.0" } ] }, { "body": "Does thyroid hormone signaling affect microRNAs expression in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22541436", "http://www.ncbi.nlm.nih.gov/pubmed/22525353", "http://www.ncbi.nlm.nih.gov/pubmed/21149577", "http://www.ncbi.nlm.nih.gov/pubmed/17379774" ], "ideal_answer": [ "YES" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.biosemantics.org/jochem#4275389", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.biosemantics.org/jochem#4250045", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974" ], "type": "yesno", "id": "516c1041298dcd4e51000070", "snippets": [ { "offsetInBeginSection": 94, "offsetInEndSection": 364, "text": "e show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541436", "endSection": "sections.0" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1240, "text": "On the other hand, T\u2083 treatment increased miR-350 expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525353", "endSection": "sections.0" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1079, "text": "Through a bioinformatics screening using TargetScan, we identified thyroid hormone receptor \u03b21 (TR\u03b21), which negatively regulates \u03b2-MHC transcription, as a target of miR-27a", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149577", "endSection": "sections.0" }, { "offsetInBeginSection": 1336, "offsetInEndSection": 1441, "text": "hese findings suggested that miR-27a regulates \u03b2-MHC gene expression by targeting TR\u03b21 in cardiomyocytes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149577", "endSection": "sections.0" }, { "offsetInBeginSection": 286, "offsetInEndSection": 500, "text": "We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17379774", "endSection": "sections.0" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1334, "text": "Moreover, miR-27a was demonstrated to modulate \u03b2-MHC gene regulation via thyroid hormone signaling and to be upregulated during the differentiation of mouse embryonic stem (ES) cells or in hypertrophic hearts in association with \u03b2-MHC gene upregulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149577", "endSection": "sections.0" } ] }, { "body": "Give examples of next-generation sequencing applications in mutation screening?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22258533", "http://www.ncbi.nlm.nih.gov/pubmed/21068339", "http://www.ncbi.nlm.nih.gov/pubmed/20569258", "http://www.ncbi.nlm.nih.gov/pubmed/21415082", "http://www.ncbi.nlm.nih.gov/pubmed/22921312", "http://www.ncbi.nlm.nih.gov/pubmed/22315491", "http://www.ncbi.nlm.nih.gov/pubmed/21897443", "http://www.ncbi.nlm.nih.gov/pubmed/21943394", "http://www.ncbi.nlm.nih.gov/pubmed/22480152", "http://www.ncbi.nlm.nih.gov/pubmed/21493627", "http://www.ncbi.nlm.nih.gov/pubmed/23420552", "http://www.ncbi.nlm.nih.gov/pubmed/21542060" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A4360575", "o": "mutation carrier screening" } ], "ideal_answer": [ "Next generation sequencing data for a particular genomic region can be seen as the summation of all the individual sequences (reads) obtained for that region and no longer as the mean of this sum as it is the case for traditional Sanger sequencing. NGS is introduced to an increasing number of mutation screening applications. An NGS based mutation screening procedure allowing the detection of inherited Alu insertions within any predefined sequence was used for the case of c.1739_1740insAlu in BRCA1 and c.156_157insAlu in BRCA2. Another NGS study screened BRCA1 and BRCA2 resulting in overall sensitivity for SOLiD and PGM of 97.8% (95% CI = 94.7 to 100.0) and 98.9% (95% CI = 96.8 to 100.0) respectively. The specificity for the SOLiD platform was high, at 100.0% (95% CI = 99.3 to 100.0). PGM correctly identified all 3 indels, but 68 false-positive indels were also called. Genes known to cause deafness were sequenced by the Illumina NGS platform. Results demonstrated that targeted exons captured by our approach achieved specificity, multiplexicity, uniformity, and depth of coverage suitable for accurate sequencing applications by the NGS systems. Reliable genotype calls for various homozygous and heterozygous mutations were achieved. In the context of von Willebrand disease 43 mutations, including 36 substitutions, 2 intronic splice site mutations, 2 indels, and 3 deletions were screened on the next-generation sequencing instrument. This demonstrated that at least 350 patients and relatives per run can be simultaneously analyzed in a fast, inexpensive manner. The Alport syndrome is caused by mutations in three key genes namely COL4A3, COL4A4 and COL4A5, each of which consists of approximately 50 exons, thus rendering mutations screening a highly time consuming and expensive endeavor. NGS is now being established for the simultaneous, fast and cost-effective detection of all possible variants in these three genes. NGS has also been used screening EGFR, KRAS and BRAF for mutations associated with cancer diagnosis and/or response to several anticancer therapies. NGS has also been used in mutation screening for hereditary spastic paraplegias, X linked leucoencephalopathy, retinitis pigmentosa, inherited urea cycle disorders, as well as the Marfan (MFS), Loeys-Dietz (LDS) and Meckel syndromes." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017421", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008403", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059014", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057166", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "summary", "id": "5148f6f0d24251bc0500003c", "snippets": [ { "offsetInBeginSection": 379, "offsetInEndSection": 615, "text": "NGS sequencing data for a particular genomic region can be seen as the summation of all the individual sequences (reads) obtained for that region and no longer as the mean of this sum as it is the case for traditional Sanger sequencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23420552", "endSection": "sections.0" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1228, "text": "Hereby we present the proof of principle of a NGS based mutation screening procedure allowing the detection of inherited Alu insertions within any predefined sequence by investigating 2 cases: c.1739_1740insAlu in BRCA1 and c.156_157insAlu in BRCA2.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23420552", "endSection": "sections.0" }, { "offsetInBeginSection": 254, "offsetInEndSection": 444, "text": "Targeted sequence data of the BRCA1 and BRCA2 genes, generated using a PCR-based, multiplexed NGS approach using the SOLiD 4 (n = 24) and Ion Torrent PGM (n = 20) next-generation sequencers,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22921312", "endSection": "sections.0" }, { "offsetInBeginSection": 513, "offsetInEndSection": 809, "text": "The overall sensitivity for SOLiD and PGM were 97.8% (95% CI = 94.7 to 100.0) and 98.9% (95% CI = 96.8 to 100.0) respectively. The specificity for the SOLiD platform was high, at 100.0% (95% CI = 99.3 to 100.0). PGM correctly identified all 3 indels, but 68 false-positive indels were also called", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22921312", "endSection": "sections.0" }, { "offsetInBeginSection": 441, "offsetInEndSection": 470, "text": "genes known to cause deafness", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480152", "endSection": "sections.0" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1215, "text": "sequenced by the Illumina NGS platform. Results demonstrated that targeted exons captured by our approach achieved specificity, multiplexicity, uniformity, and depth of coverage suitable for accurate sequencing applications by the NGS systems. Reliable genotype calls for various homozygous and heterozygous mutations were achieved.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480152", "endSection": "sections.0" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1442, "text": "The method validated here could be readily expanded to include all-known deafness genes for applications such as genetic hearing screening in newborns", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22480152", "endSection": "sections.0" }, { "offsetInBeginSection": 292, "offsetInEndSection": 342, "text": "applying this technology to von Willebrand disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315491", "endSection": "sections.0" }, { "offsetInBeginSection": 544, "offsetInEndSection": 646, "text": "43 mutations, including 36 substitutions, 2 intronic splice site mutations, 2 indels, and 3 deletions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315491", "endSection": "sections.0" }, { "offsetInBeginSection": 777, "offsetInEndSection": 928, "text": "on the next-generation sequencing instrument, at least 350 patients and relatives per run can be simultaneously analyzed in a fast, inexpensive manner.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315491", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258533", "endSection": "sections.0" }, { "offsetInBeginSection": 362, "offsetInEndSection": 457, "text": "We used next-generation sequencing focused on the SPG30 chromosomal region on chromosome 2q37.3", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258533", "endSection": "sections.0" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1572, "text": "We have shown that mutations in the KIF1A gene are responsible for SPG30 in two autosomal recessive HSP families. In published families, the nature of the KIF1A mutations seems to be of good predictor of the underlying phenotype and vice versa.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258533", "endSection": "sections.0" }, { "offsetInBeginSection": 123, "offsetInEndSection": 283, "text": "Mutations in the COL4A5 gene cause X-linked ATS. Mutations in COL4A4 and COL4A3 genes have been reported in both autosomal recessive and autosomal dominant ATS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21897443", "endSection": "sections.0" }, { "offsetInBeginSection": 651, "offsetInEndSection": 932, "text": "To overcome these limitations, we designed a next-generation sequencing (NGS) protocol enabling simultaneous detection of all possible variants in the three genes. We used a method coupling selective amplification to the 454 Roche DNA sequencing platform (Genome Sequencer junior).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21897443", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The Marfan (MFS) and Loeys-Dietz (LDS) syndromes are caused by mutations in the fibrillin-1 (FBN1) and Transforming Growth Factor Beta Receptor 1 and 2 (TGFBR1 and TGFBR2) genes, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542060", "endSection": "sections.0" }, { "offsetInBeginSection": 319, "offsetInEndSection": 458, "text": "We have tailored a cost-effective and reliable mutation discovery strategy using multiplex PCR followed by Next Generation Sequencing (NGS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542060", "endSection": "sections.0" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1427, "text": "We conclude that multiplex PCR of all coding exons of FBN1 and TGFBR1/2 followed by NGS analysis and MLPA is a robust strategy for time- and cost-effective identification of mutations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542060", "endSection": "sections.0" }, { "offsetInBeginSection": 298, "offsetInEndSection": 411, "text": "To date, six genes have been commonly associated with MKS (MKS1, TMEM67, TMEM216, CEP290, CC2D2A and RPGRIP1L). H", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21493627", "endSection": "sections.0" }, { "offsetInBeginSection": 597, "offsetInEndSection": 830, "text": "To explore the full genetic complexity of MKS, we performed exon-enriched next-generation sequencing of 31 ciliopathy genes in 12 MKS pedigrees using RainDance microdroplet-PCR enrichment and IlluminaGAIIx next-generation sequencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21493627", "endSection": "sections.0" }, { "offsetInBeginSection": 198, "offsetInEndSection": 333, "text": "o carry out exome sequencing of entire transcripts of the whole X chromosome to investigate a family with X linked leucoencephalopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415082", "endSection": "sections.0" }, { "offsetInBeginSection": 343, "offsetInEndSection": 413, "text": "Next-generation sequencing of all the transcripts of the X chromosome,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415082", "endSection": "sections.0" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1274, "text": "Single-lane exome next-generation sequencing is sufficient to fully analyse all the transcripts of the X chromosome. This method is particularly suitable for mutation screening of X-linked recessive disorders and can avoid biases in candidate gene choice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415082", "endSection": "sections.0" }, { "offsetInBeginSection": 75, "offsetInEndSection": 125, "text": "diagnoses of inherited urea cycle disorders (UCDs)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21068339", "endSection": "sections.0" }, { "offsetInBeginSection": 880, "offsetInEndSection": 939, "text": "We used the Genome Sequencer FLX System (454 Life Sciences)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21068339", "endSection": "sections.0" } ] }, { "body": "List common features of Shapiro syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7565067", "http://www.ncbi.nlm.nih.gov/pubmed/24339619", "http://www.ncbi.nlm.nih.gov/pubmed/23578790", "http://www.ncbi.nlm.nih.gov/pubmed/24187634", "http://www.ncbi.nlm.nih.gov/pubmed/21041995", "http://www.ncbi.nlm.nih.gov/pubmed/19027594" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18458850", "o": "C537594" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18471145", "o": "Recurrent spontaneous hypothermia with hypoplasia of the corpus callosum" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18465004", "o": "Shapiro syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18458850", "o": "Shapiro's syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2931542", "o": "http://linkedlifedata.com/resource/umls/label/A18471145" }, { "p": 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"o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2931542", "o": "http://linkedlifedata.com/resource/umls/id/C0796147" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1702570", "o": "acrocallosal syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1702533", "o": "acrocallosal syndrome (ACS)" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18440175", "o": "Acrocallosal Syndrome [Disease/Finding]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11975298", "o": "ACROCALLOSAL SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1701640", "o": "Schinzel syndrome 1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12032571", "o": "ACLS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17700774", "o": "Acrocallosal Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11961004", "o": "HALLUX DUPLICATION, POSTAXIAL POLYDACTYLY, AND ABSENCE OF CORPUS CALLOSUM" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0796147", "o": "http://linkedlifedata.com/resource/umls/id/C2931542" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasSymptom", "s": "http://linkedlifedata.com/resource/umls/id/C2931542", "o": "http://linkedlifedata.com/resource/umls/id/C0020672" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17699101", "o": "BODY TEMPERATURE, DECREASED" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0393370", "o": "BODY TEMPERATURE LOW" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1144305", "o": "hypothermia, natural" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17992132", "o": "Hypothermia [Disease/Finding]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0463819", "o": "TEMPERATURE BODY DECREASE" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17678862", "o": "TEMPERATURE, DECREASED BODY" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0419736", "o": "HYPOPYREXIA" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17822767", "o": "hypothermia NOS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10802646", "o": "Decreased Core Body Temperature" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8311249", "o": "Hypothermia" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0419764", "o": "HYPOTHERMIA" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0393367", "o": "BODY TEMPERATURE DECREASED" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0481466", "o": "hypothermia" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0071500", "o": "Hypothermias" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17699102", "o": "DECREASED BODY TEMPERATURE" } ], "ideal_answer": [ "Shapiro syndrome is a rare entity, comprising a triad of recurrent hypothermia, hyperhidrosis and congenital agenesis of the corpus callosum. Hypermelatoninemia has also been described in a patient with Shapiro syndrome." ], "exact_answer": [ [ "recurrent hypothermia" ], [ "hyperhidrosis" ], [ "congenital agenesis of the corpus callosum" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "list", "id": "5314c7afdae131f84700000a", "snippets": [ { "offsetInBeginSection": 106, "offsetInEndSection": 266, "text": "Shapiro syndrome is defined as the constellation of periodic hypothermia and hyperhidrosis along with agenesis of the corpus callosum by Shapiro et al. in 1969.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24187634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Shapiro syndrome is a rare entity, comprising a triad of recurrent hypothermia, hyperhidrosis and congenital agenesis of the corpus callosum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23578790", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 600, "text": "We present a case of an 80 year old woman presenting with recurrent bouts of shivering, sweating and profound malaise, who sought medical attention because the frequency and severity of attacks worsened in her later years. MRI Brain demonstrated agenesis of the corpus callosum; a rigorous work-up excluded other causes for her symptomatology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23578790", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1138, "text": "These findings imply that aberrant thermoregulation in Shapiro syndrome involves a number of structures remote from the callosal region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23578790", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 552, "text": "A 6-year-old girl previously diagnosed with Shapiro's syndrome was admitted to our hospital on several occasions during a 1-year period with complaints of altered consciousness, syncope, hypothermia and episodes of sweating.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21041995", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1470, "text": "Hypermelatoninemia should be considered in patients with spontaneous periodic hypothermia and hyperhidrosis, and also in patients with Shapiro's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21041995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "We present a patient diagnosed with Shapiro syndrome without corpus callosum agenesis. A 4-year-old-girl was admitted to the hospital with complaints of sweating, cooling, and drowsiness that continued during the last week of her admission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19027594", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1686, "text": "Postmortem data regarding the hypothalamic and surrounding areas from future cases of Shapiro syndrome and spontaneous periodic hypothermia would be of great interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7565067", "endSection": "abstract" } ] }, { "body": "List mouse models for autism spectrum disorder (ASD).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22726567", "http://www.ncbi.nlm.nih.gov/pubmed/24096295", "http://www.ncbi.nlm.nih.gov/pubmed/24293564", "http://www.ncbi.nlm.nih.gov/pubmed/23516405", "http://www.ncbi.nlm.nih.gov/pubmed/22560338", "http://www.ncbi.nlm.nih.gov/pubmed/20699105", "http://www.ncbi.nlm.nih.gov/pubmed/23536326", "http://www.ncbi.nlm.nih.gov/pubmed/22016815", "http://www.ncbi.nlm.nih.gov/pubmed/23994547", "http://www.ncbi.nlm.nih.gov/pubmed/23270976", "http://www.ncbi.nlm.nih.gov/pubmed/22492990", "http://www.ncbi.nlm.nih.gov/pubmed/22802640", "http://www.ncbi.nlm.nih.gov/pubmed/21079609", "http://www.ncbi.nlm.nih.gov/pubmed/21484200", "http://www.ncbi.nlm.nih.gov/pubmed/22958973", "http://www.ncbi.nlm.nih.gov/pubmed/23621888", "http://www.ncbi.nlm.nih.gov/pubmed/24211371", "http://www.ncbi.nlm.nih.gov/pubmed/22249109", "http://www.ncbi.nlm.nih.gov/pubmed/21878566", "http://www.ncbi.nlm.nih.gov/pubmed/24124122", "http://www.ncbi.nlm.nih.gov/pubmed/21908517", "http://www.ncbi.nlm.nih.gov/pubmed/24315484", "http://www.ncbi.nlm.nih.gov/pubmed/23141534", "http://www.ncbi.nlm.nih.gov/pubmed/23123587", "http://www.ncbi.nlm.nih.gov/pubmed/21182206", "http://www.ncbi.nlm.nih.gov/pubmed/22677272", "http://www.ncbi.nlm.nih.gov/pubmed/21093492" ], "ideal_answer": [ "Numerous mouse models exists for autism spectrum disorder, such as: BTBR T+tf/J (BTBR), maternal immune, activation (MIA) mouse model of gestational poly(IC) exposure, C58/J and ProSAP1/Shank2." ], "exact_answer": [ [ "maternal immune activation (MIA) mouse model of gestational poly(IC) exposure", "C58/J", "Grin1", "Shank3-deficient mice", "C57BL/6J", "SYNGAP1", "Tsc2f/-", "MALTT", "(Dp(11)17/+)", "NR1(neo-/-)", "TS2-neo mouse", "Tbx1 heterozygous (HT) mice" ], [ "BTBR T+tf/J (BTBR)", "VPA600", "ProSAP1/Shank2" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008957", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008962", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004195", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018345", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008822", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023421", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008818", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051379" ], "type": "list", "id": "52f5417b2059c6d71c000024", "snippets": [ { "offsetInBeginSection": 275, "offsetInEndSection": 361, "text": "maternal immune activation (MIA) mouse model that is known to display features of ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24315484", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 599, "text": "BTBR T+tf/J (BTBR), a model of ASD with cognitive deficits,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293564", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 574, "text": "C58/J mouse strain, a model of ASD core symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211371", "endSection": "abstract" }, { "offsetInBeginSection": 67, "offsetInEndSection": 98, "text": "the C58/J mouse model of autism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211371", "endSection": "title" }, { "offsetInBeginSection": 865, "offsetInEndSection": 938, "text": "Both C58/J and Grin1 knockdown mice, another model of ASD-like behavior, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211371", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 498, "text": "Mice injected subcutaneously with 600\u2009mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24124122", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 852, "text": "BTBR T+tf/J (BTBR), a commonly-used model presenting all core autism-related phenotypes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "The Autism ProSAP1/Shank2 mouse model ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23994547", "endSection": "title" }, { "offsetInBeginSection": 843, "offsetInEndSection": 864, "text": "Shank3-deficient mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621888", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 629, "text": "a panel of Shank mutant mouse models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23536326", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 682, "text": "maternal immune activation (MIA) mouse model of gestational poly(IC) exposure ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516405", "endSection": "abstract" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1473, "text": "poly(IC) mouse model of autism spectrum disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516405", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 124, "text": "BTBR T+ tf/J strain, a mouse model of autism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23270976", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 193, "text": "The inbred BTBR T+ tf/J (BTBR) strain, a putative mouse model of autism,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23270976", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 336, "text": "C57BL/6J strain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23270976", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 285, "text": "SYNGAP1 mouse model of ID/ASD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23141534", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 787, "text": "Tsc2f/-;Cre mice demonstrated increased repetitive behavior as assessed with marble burying activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123587", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 58, "text": "BTBR T+ tf/J mouse model for autism spectrum disorders", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22958973", "endSection": "title" }, { "offsetInBeginSection": 223, "offsetInEndSection": 314, "text": "Furthermore, maternal infection (maternal immune activation, MIA) is a risk factor for ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22802640", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 431, "text": "NR1(neo-/-) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726567", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 620, "text": "mice heterozygous for the Gabrb3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20699105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Gestational immune activation and Tsc2 haploinsufficiency", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21079609", "endSection": "title" }, { "offsetInBeginSection": 402, "offsetInEndSection": 432, "text": "novel transgenic mouse, MALTT,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21093492", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 416, "text": "sing a mouse model, CD38, a transmembrane protein expressed in immune cells but also in brain, was found to be critical for social behavior via regulation of oxytocin secretion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21182206", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 587, "text": "fmr1 knockout mouse model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21484200", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1132, "text": "TS2-neo mouse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21878566", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 735, "text": "Congenic Tbx1 heterozygous (HT) mice ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21908517", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 689, "text": "the valproic acid (VPA) mouse model of autism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016815", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1696, "text": " indicates that the MeCP2+/- model may be useful for preclinical development targeting specific cortical processing abnormalities in RTT with potential relevance to ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249109", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 391, "text": "(Dp(11)17/+) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BTBR T+tf/J (BTBR) inbred mice are frequently used as a model of autism spectrum disorders (ASD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22677272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Intact and impaired executive abilities in the BTBR mouse model of autism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22677272", "endSection": "title" } ] }, { "body": "What is BioASQ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25925131" ], "ideal_answer": [ "BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies. ", "The BioASQ challenge is a competition on large-scale biomedical semantic indexing and question answering (QA). BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies. BIOASQ helped obtain a unified view of how techniques from text classification, semantic indexing, document and passage retrieval, question answering, and text summarization can be combined to allow biomedical experts to obtain concise, user-understandable answers to questions reflecting their real information needs." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012660" ], "type": "summary", "id": "56ae3cdc0a360a5e45000008", "snippets": [ { "offsetInBeginSection": 2104, "offsetInEndSection": 2422, "text": "BIOASQ helped obtain a unified view of how techniques from text classification, semantic indexing, document and passage retrieval, question answering, and text summarization can be combined to allow biomedical experts to obtain concise, user-understandable answers to questions reflecting their real information needs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 485, "text": "BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 214, "text": "This article provides an overview of the first BIOASQ challenge, a competition on large-scale biomedical semantic indexing and question answering (QA), which took place between March and September 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "This article provides an overview of the first BIOASQ challenge, a competition on large-scale biomedical semantic indexing and question answering (QA), which took place between March and September 2013", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 472, "text": "BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 564, "text": "BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies.RESULTS: The 2013 BIOASQ competition comprised two tasks, Task 1a and Task 1b. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1858, "text": "The BIOASQ infrastructure, including benchmark datasets, evaluation mechanisms, and the results of the participants and baseline methods, is publicly available.CONCLUSIONS: A publicly available evaluation infrastructure for biomedical semantic indexing and QA has been developed, which includes benchmark datasets, and can be used to evaluate systems that: assign MESH headings to published articles or to English questions; retrieve relevant RDF triples from ontologies, relevant articles and snippets from PUBMED Central; produce \"exact\" and paragraph-sized \"ideal\" answers (summaries). The results of the systems that participated in the 2013 BIOASQ competition are promising. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 1946, "offsetInEndSection": 2422, "text": "In Task 1b the systems received high scores in the manual evaluation of the \"ideal\" answers; hence, they produced high quality summaries as answers. Overall, BIOASQ helped obtain a unified view of how techniques from text classification, semantic indexing, document and passage retrieval, question answering, and text summarization can be combined to allow biomedical experts to obtain concise, user-understandable answers to questions reflecting their real information needs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 2095, "offsetInEndSection": 2422, "text": "Overall, BIOASQ helped obtain a unified view of how techniques from text classification, semantic indexing, document and passage retrieval, question answering, and text summarization can be combined to allow biomedical experts to obtain concise, user-understandable answers to questions reflecting their real information needs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "BACKGROUND: This article provides an overview of the first BIOASQ challenge, a competition on large-scale biomedical semantic indexing and question answering (QA), which took place between March and September 2013. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "This article provides an overview of the first BIOASQ challenge, a competition on large-scale biomedical semantic indexing and question answering (QA), which took place between March and September 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 544, "text": "BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies. The 2013 BIOASQ competition comprised two tasks, Task 1a and Task 1b.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 474, "text": "This article provides an overview of the first BIOASQ challenge, a competition on large-scale biomedical semantic indexing and question answering (QA), which took place between March and September 2013. BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 544, "text": "BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies.The 2013 BIOASQ competition comprised two tasks, Task 1a and Task 1b.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25925131", "endSection": "abstract" } ] }, { "body": "Which are the main functions of G3BP1 and G3BP2 proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24321297", "http://www.ncbi.nlm.nih.gov/pubmed/20392851", "http://www.ncbi.nlm.nih.gov/pubmed/18079183", "http://www.ncbi.nlm.nih.gov/pubmed/21957497", "http://www.ncbi.nlm.nih.gov/pubmed/24992036", "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "http://www.ncbi.nlm.nih.gov/pubmed/22703643", "http://www.ncbi.nlm.nih.gov/pubmed/17297477" ], "ideal_answer": [ "The main functions of G3BP1 and/or G3BP2 include translation of interferon stimulated mRNAs during dengue virus infection, initiation of assembly of stress granules, regulation of PMP22 mRNA which was found to affect cell proliferation in breast cancer cells, participation in several signaling pathways involved in growth, differentiation and apoptosis in human tumor cells after overexpression, limit viral replication events during Sindbis virus (SINV) infection, and modulation of p53 and MDM2 activity." ], "exact_answer": [ [ "Translation of interferon stimulated mRNAs during dengue virus infection" ], [ "Initiation of assembly of stress granules" ], [ "Regulation of PMP22 mRNA which was found to affect cell proliferation in breast cancer cells" ], [ "Participation in several signaling pathways involved in growth, differentiation and apoptosis in human tumor cells after overexpression" ], [ "Limit viral replication events during Sindbis virus (SINV) infection" ], [ "Modulation of p53 and MDM2 activity" ] ], "type": "list", "id": "5717ab7ccb4ef8864c00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Both G3BP1 and G3BP2 contribute to stress granule formation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24992036", "endSection": "title" }, { "offsetInBeginSection": 200, "offsetInEndSection": 406, "text": "We examined three conserved host RNA-binding proteins (RBPs) G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2) infection and found them to be novel regulators of the interferon (IFN) response against DENV-2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24992036", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 675, "text": "Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 964, "text": "Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1118, "text": "like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1290, "text": "Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321297", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 379, "text": "G3BP has been reported to both stabilize and induce degradation of specific mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321297", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 791, "text": "Global gene expression analyses of G3BP1- and G3BP2-depleted cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was significantly influenced by G3BP1 depletion which led to a 2-3 fold increased expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321297", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 928, "text": "Depletion of PMP22 resulted in increased proliferation and the G3BP1-mediated effect on proliferation was not seen upon PMP22-depletion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Ras-GTPase-activating protein SH3 domain-binding proteins (G3BP) are overexpressed in various human tumors and participate in several signaling pathways involved in growth, differentiation and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22703643", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1219, "text": "Two related proteins found in association with nsP4 at both times of infection, GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) and G3BP2 were also previously identified as associated with SINV nsP2 and nsP3. We demonstrate a likely overlapping role for these host factors in limiting SINV replication events", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20392851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Modulation of p53 and MDM2 activity by novel interaction with Ras-GAP binding proteins (G3BP)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17297477", "endSection": "title" }, { "offsetInBeginSection": 308, "offsetInEndSection": 922, "text": "we have found that members of the Ras network of proteins, Ras-GTPase activating protein-SH3-domain-binding proteins 1 and 2 (G3BP1 and 2), bind to p53 in vitro and in vivo. Our data show that expression of G3BPs leads to the redistribution of p53 from the nucleus to the cytoplasm. The G3BP2 isoform additionally associated with murine double minute 2 (MDM2), a negative regulator of p53. G3BP2 expression resulted in significant reduction in MDM2-mediated p53 ubiquitylation and degradation. Interestingly, MDM2 was also stabilized in G3BP2-expressing cells and its ability to ubiquitylate itself was compromised", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17297477", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 994, "text": "We identified several proteins, including DDX6, G3BP1, G3BP2, Caprin1, and USP10, implicated in P body (PB) and stress granule (SG) function, and not previously known to bind DENV RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957497", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1570, "text": "Additional experiments demonstrate that, in contrast to DDX6, the SG proteins G3BP1, G3BP2, Caprin1 and USP10 bind to the variable region (VR) in the 3' UTR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24992036", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Both G3BP1 and G3BP2 contribute to stress granule formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "title" }, { "offsetInBeginSection": 767, "offsetInEndSection": 966, "text": "Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1291, "text": "Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1186, "text": "Furthermore, expression of shRNA targeting either G3BP1 or G3BP2 in human cancer cell lines resulted in marked upregulation of p53 levels and activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17297477", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 676, "text": "Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 965, "text": "Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1119, "text": "Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279204", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 540, "text": "We found that HDAC6 interacts with another SG protein, G3BP (Ras-GTPase-activating protein SH3 domain-binding protein 1), and localizes to SGs under all stress conditions tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18079183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 816, "text": "Dengue virus (DENV) is a rapidly re-emerging flavivirus that causes dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), diseases for which there are no available therapies or vaccines.\u00a0 The DENV-2 positive-strand RNA genome contains 5' and 3' untranslated regions (UTRs) that have been shown to form secondary structures required for virus replication and interaction with host cell proteins.\u00a0 In order to comprehensively identify host cell factors that bind the DENV-2 UTRs, we performed RNA chromatography, using the DENV-2 5' and 3' UTRs as \"bait\", combined with quantitative mass spectrometry.\u00a0 We identified several proteins, including DDX6, G3BP1, G3BP2, Caprin1, and USP10, implicated in P body (PB) and stress granule (SG) function, and not previously known to bind DENV RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957497", "endSection": "abstract" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1427, "text": "\u00a0Additional experiments demonstrate that, in contrast to DDX6, the SG proteins G3BP1, G3BP2, Caprin1 and USP10 bind to the variable region (VR) in the 3' UTR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957497", "endSection": "abstract" } ] }, { "body": "What is the definitive treatment for low pressure headache?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19665883", "http://www.ncbi.nlm.nih.gov/pubmed/20814596", "http://www.ncbi.nlm.nih.gov/pubmed/22705138", "http://www.ncbi.nlm.nih.gov/pubmed/21461591", "http://www.ncbi.nlm.nih.gov/pubmed/16244018", "http://www.ncbi.nlm.nih.gov/pubmed/17961846", "http://www.ncbi.nlm.nih.gov/pubmed/8570054", "http://www.ncbi.nlm.nih.gov/pubmed/14529014", "http://www.ncbi.nlm.nih.gov/pubmed/23533436" ], "ideal_answer": [ "epidural blood patch" ], "exact_answer": [ "epidural blood patch" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006261", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020773" ], "type": "factoid", "id": "53262cdcd6d3ac6a34000003", "snippets": [ { "offsetInBeginSection": 147, "offsetInEndSection": 258, "text": "This was initially treated with analgesia, caffeine, and fluids for the presumed cerebrospinal fluid (CSF) leak", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533436", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 471, "text": "she was treated for CSF leak using an epidural blood patch.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533436", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 487, "text": "Epidural blood patching may be necessary to seal the leak - CT fluoroscopy may be helpful in delivering the patch directly to the site of the leak", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22705138", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 435, "text": " invasive measures with epidural blood patch providing the cornerstone of the invasive measures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21461591", "endSection": "abstract" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1567, "text": "However the present results, allows us to conclude that EBP in treatment-refractory low CSF pressure headache can be considered as a treatment option.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21461591", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 807, "text": "In high-risk patients , for example, age < 50 years, postpartum, large-gauge needle puncture, epidural blood patch should be performed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20814596", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 439, "text": "Both parturients were successfully managed using acupuncture rather than an epidural blood patch.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19665883", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1054, "text": "The weight of existing literature supports EBP as an initial treatment of SIH, although its effectiveness does not approach that seen when EBP is used to treat meningeal puncture headache.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17961846", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 335, "text": "In this case, a 17-yr-old girl had symptoms of a low-pressure headache after LP shunt placement alleviated by an epidural blood patch.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16244018", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 962, "text": "In high-risk patients (e.g. age < 50 years, post-partum, large-gauge-needle puncture), patients should be offered early (within 24-48 h of dural puncture) epidural blood patch", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14529014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "We describe thickening and contrast enhancement of the intracranial pachymeninges, revealed by MRI in a patient with presumed low-pressure headache following dural puncture and a blood patch", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8570054", "endSection": "abstract" } ] }, { "body": "What is the role of the histidine rich calcium binding protein (HRC) in cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17499229", "http://www.ncbi.nlm.nih.gov/pubmed/18617481", "http://www.ncbi.nlm.nih.gov/pubmed/21742996" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0594280", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513348593037001D", "o": "hrcS" } ], "ideal_answer": [ "The histidine-rich Ca-binding protein (HRC), a 165 kDa sarcoplasmic reticulum (SR) protein, regulates SR Ca cycling during excitation\u2013contraction coupling. HRC mutations or polymorphisms lead to cardiac dysfunction. The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias and sudden death in idiopathic dilated cardiomyopathy (DCM)." ], "concepts": [ "http://www.uniprot.org/uniprot/SRCH_RABIT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311" ], "type": "summary", "id": "51542de6d24251bc0500007f", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 462, "text": "The histidine-rich Ca-binding protein (HRC) is a Ca-storage protein in cardiac sarcoplasmic reticulum. Recent transgenic studies revealed that this protein inhibits the maximal rates of sarcoplasmic reticulum Ca-transport, leading to cardiac dysfunction. In view of the role of sarcoplasmic reticulum Ca-cycling in myocardial ischemia/reperfusion injury, we designed this study to gain further insight into the role of HRC during ischemia/reperfusion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17499229", "endSection": "sections.0" }, { "offsetInBeginSection": 1896, "offsetInEndSection": 2080, "text": "Our findings suggest that increased cardiac HRC expression protects against ischemia/reperfusion injury in the heart, resulting in improved recovery of function and reduced infarction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17499229", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "endSection": "sections.0" }, { "offsetInBeginSection": 530, "offsetInEndSection": 1527, "text": "The HRC(S96A) mutant exacerbated the inhibitory effects of HRC(WT) on the amplitude of Ca(2+) transients, prolongation of Ca(2+) decay time, and caffeine-induced sarcoplasmic reticulum Ca(2+) release. Consistent with these findings, HRC(S96A) reduced maximal sarcoplasmic reticulum calcium uptake rate to a higher extent than HRC(WT). Furthermore, the frequency of spontaneous Ca(2+) sparks, which was reduced by HRC(WT), was increased by mutant HRC(S96A) under resting conditions although there were no spontaneous Ca(2+) waves under stress conditions. However, expression of the HRC(S96A) genetic variant in cardiomyocytes from a rat model of postmyocardial infarction heart failure induced dramatic disturbances of rhythmic Ca(2+) transients. These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "endSection": "sections.0" } ] }, { "body": "What is the incidence of sudden cardiac death among young athletes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19734497", "http://www.ncbi.nlm.nih.gov/pubmed/22362900", "http://www.ncbi.nlm.nih.gov/pubmed/17143117", "http://www.ncbi.nlm.nih.gov/pubmed/19587604", "http://www.ncbi.nlm.nih.gov/pubmed/17330410", "http://www.ncbi.nlm.nih.gov/pubmed/20682064" ], "ideal_answer": [ "the incidence of sudden cardiac death among young athletes ranges from 0.5 to 3 per 100,000 athletes per year ." ], "exact_answer": [ "0.5 to 3 per 100,000 athletes per year" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016757", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055815", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015994", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ], "type": "factoid", "id": "53036faab24d855b11000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Sudden cardiac death is the leading cause of mortality among young athletes with an incidence of 1-2 per 100,000 athletes per annum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362900", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 478, "text": "The incidence of SCD is expected at one case for each 200,000 young athletes per year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20682064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The incidence of sudden cardiac death (SCD) among young athletes is estimated to be 1-3 per 100,000 person years, and may be underestimated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19734497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Sudden cardiac death in a young athlete is a tragic and marking event, even though the media attention it gets is more important than its incidence (1-2/100000 per year). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17330410", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 516, "text": "The sudden death of athletes under 35 years engaged in competitive sports is a well-known occurrence; the incidence is higher in athletes (approximately 2/100,000 per year) than in non-athletes (2.5 : 1), and the cause is cardiovascular in over 90%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17143117", "endSection": "abstract" } ] }, { "body": "What is the effect of amitriptyline in the mdx mouse model of Duchenne muscular dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24972834" ], "ideal_answer": [ "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy", "Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. On the other hand, inflammation in mdx skeletal muscle tissue was also reduced as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-\u03b1 and interleukin-6 in the forelimb flexors.", "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy " ], "type": "summary", "id": "5713506d1174fb1755000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "title" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1252, "text": "Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1643, "text": " Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-\u03b1 and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor- and interleukin-6 in the forelimb flexors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1253, "text": "Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 1254, "offsetInEndSection": 1527, "text": "Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-\u03b1 and interleukin-6 in the forelimb flexors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1824, "text": "Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "title" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1645, "text": "Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1254, "text": "Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" }, { "offsetInBeginSection": 1646, "offsetInEndSection": 1824, "text": "Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24972834", "endSection": "abstract" } ] }, { "body": "Which post-translational histone modifications are characteristic of facultative heterochromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25938714", "http://www.ncbi.nlm.nih.gov/pubmed/19515781", "http://www.ncbi.nlm.nih.gov/pubmed/23645681", "http://www.ncbi.nlm.nih.gov/pubmed/16648823", "http://www.ncbi.nlm.nih.gov/pubmed/26430472", "http://www.ncbi.nlm.nih.gov/pubmed/21803857" ], "ideal_answer": [ "Nuclear VapB methyltransferase diminishes the establishment of facultative heterochromatin by decreasing histone 3 lysine 9 trimethylation (H3K9me3). Dramatic changes in exposure of a repressive chromatin mark, H3K9me2, indicate that during development linker histone plays a role in establishing the facultative heterochromatin territory and architecture in the nucleus. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin." ], "exact_answer": [ [ "H3K9me3" ], [ "H3K9me2" ], [ "H3K36me3" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0051567", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006570", "http://amigo.geneontology.org/amigo/term/GO:0000792", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657" ], "type": "list", "id": "56c6dc6f5795f9a73e000007", "snippets": [ { "offsetInBeginSection": 732, "offsetInEndSection": 1151, "text": "We used chromatin immunoprecipitation combined with high-throughput sequencing (\"ChIP-seq\") of DNA associated with the centromere-specific histone H3, CENP-A (CenH3), to identify centromeric DNA, and ChIP-seq with antibodies against dimethylated H3K4, trimethylated H3K9 and trimethylated H3K27 to determine the relative distribution and proportion of euchromatin, obligate and facultative heterochromatin, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26430472", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1128, "text": "Dramatic changes in exposure of a repressive chromatin mark, H3K9me2, indicate that during development linker histone plays a role in establishing the facultative heterochromatin territory and architecture in the nucleus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23645681", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 897, "text": "We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3. Strikingly, we found that trimethylated histone H3 at lysine 36 (H3K36me3), which was previously identified as a hallmark of actively transcribed regions, is deposited onto the silenced, maternally contributed 3-Mb imprinted region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "title" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1276, "text": "In addition, we demonstrate that H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in mouse embryonic stem cells and fibroblasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803857", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 855, "text": "Remarkably, H3K9me3 is predominant in coding regions of active genes, a phenomenon that is not restricted to the X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648823", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1106, "text": "We detected the H3K9me2, H3K9me3, and H3K27me3 modifications, with H3K27me3, which is indicative of facultative heterochromatin, exhibiting the highest enrichment on all viral promoters tested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19515781", "endSection": "abstract" }, { "offsetInBeginSection": 1646, "offsetInEndSection": 1851, "text": "Our study identifies a unique heterochromatin state marked by the presence of both H3.3 and H3K9me3, and establishes an important role for H3.3 in control of ERV retrotransposition in embryonic stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25938714", "endSection": "abstract" } ] }, { "body": "Mutations in which genes have been associated with Aicardi-Goutieres syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23365100", "http://www.ncbi.nlm.nih.gov/pubmed/19034401", "http://www.ncbi.nlm.nih.gov/pubmed/25500879", "http://www.ncbi.nlm.nih.gov/pubmed/17846997", "http://www.ncbi.nlm.nih.gov/pubmed/24183309", "http://www.ncbi.nlm.nih.gov/pubmed/21808053" ], "ideal_answer": [ "Aicardi-Gouti\u00e8res syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR)." ], "exact_answer": [ [ "TREX1" ], [ "RNASEH2A" ], [ "RNASEH2B" ], [ "RNASEH2C" ], [ "SAMHD1" ], [ "ADAR" ] ], "concepts": [ "http://www.uniprot.org/uniprot/RNH2A_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058540", "http://www.disease-ontology.org/api/metadata/DOID:0050629", "http://www.disease-ontology.org/api/metadata/DOID:8461", "http://www.uniprot.org/uniprot/RNH2C_HUMAN", "http://www.uniprot.org/uniprot/RNH2B_HUMAN" ], "type": "list", "id": "56f5692f09dd18d46b00000a", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 170, "text": "Aicardi-Gouti\u00e8res syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Aicardi-Gouti\u00e8res syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183309", "endSection": "abstract" } ] }, { "body": "List bacteria that may be useful in uranium bioremediation.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19717633", "http://www.ncbi.nlm.nih.gov/pubmed/15819846", "http://www.ncbi.nlm.nih.gov/pubmed/18378664", "http://www.ncbi.nlm.nih.gov/pubmed/11976101", "http://www.ncbi.nlm.nih.gov/pubmed/23038171", "http://www.ncbi.nlm.nih.gov/pubmed/21112694", "http://www.ncbi.nlm.nih.gov/pubmed/12368813", "http://www.ncbi.nlm.nih.gov/pubmed/23446832", "http://www.ncbi.nlm.nih.gov/pubmed/22327592", "http://www.ncbi.nlm.nih.gov/pubmed/19651424", "http://www.ncbi.nlm.nih.gov/pubmed/19129865", "http://www.ncbi.nlm.nih.gov/pubmed/18451051", "http://www.ncbi.nlm.nih.gov/pubmed/21337330", "http://www.ncbi.nlm.nih.gov/pubmed/21255372", "http://www.ncbi.nlm.nih.gov/pubmed/23275510", "http://www.ncbi.nlm.nih.gov/pubmed/12788780", "http://www.ncbi.nlm.nih.gov/pubmed/16204552", "http://www.ncbi.nlm.nih.gov/pubmed/22510989", "http://www.ncbi.nlm.nih.gov/pubmed/22432531", "http://www.ncbi.nlm.nih.gov/pubmed/18497157", "http://www.ncbi.nlm.nih.gov/pubmed/18843300", "http://www.ncbi.nlm.nih.gov/pubmed/12626092", "http://www.ncbi.nlm.nih.gov/pubmed/19346346", "http://www.ncbi.nlm.nih.gov/pubmed/18279349", "http://www.ncbi.nlm.nih.gov/pubmed/21261921", "http://www.ncbi.nlm.nih.gov/pubmed/20010635", "http://www.ncbi.nlm.nih.gov/pubmed/18450691", "http://www.ncbi.nlm.nih.gov/pubmed/18059491", "http://www.ncbi.nlm.nih.gov/pubmed/23416228", "http://www.ncbi.nlm.nih.gov/pubmed/23894087" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7801424", "o": "D001673" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0598015", "o": "http://linkedlifedata.com/resource/umls/label/A1303884" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0598015", "o": "http://linkedlifedata.com/resource/umls/label/A7801424" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1303884", "o": "bioremediation" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7801424", "o": "Bioremediation" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7801424", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1303884", "o": "1850-1558" } ], "ideal_answer": [ "The main bacteria studied in uranium bioremediation are Geobacteraceae. Other bacteria are: \nFirmicutes, \nShewanella oneidensis\nPseudomonas aeruginosa\nAnaeromyxobacter dehalogenans \nstrain Rf4T" ], "exact_answer": [ [ "Betaproteobacteria" ], [ "Firmicutes" ], [ "Geobacter", "Geobacteraceae", "Geobacter uraniireducens" ], [ "Shewanella oneidensis" ], [ "Pseudomonas aeruginosa" ], [ "Anaeromyxobacter dehalogenans" ], [ "strain Rf4T" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014501", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001673", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017974", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001419", "http://www.biosemantics.org/jochem#4278179" ], "type": "list", "id": "530a3e18970c65fa6b000005", "snippets": [ { "offsetInBeginSection": 406, "offsetInEndSection": 588, "text": "Members of the Betaproteobacteria (i.e. Dechloromonas, Ralstonia, Rhodoferax, Polaromonas, Delftia, Chromobacterium) and the Firmicutes dominated the biostimulated aquifer community.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Shewanella oneidensis is an important model organism for bioremediation studies because of its diverse respiratory capabilities, conferred in part by multicomponent, branched electron transport systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12368813", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 719, "text": "metal-reducing Geobacter species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446832", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 1066, "text": " Identifications based on bacterial 16S rRNA sequence analysis showed that the dominant cultivable bacteria belonged to the genus Bacillus. Members of the genera Paenibacillus, Lysinibacillus, Klebsiella, Microbacterium and Chryseobacterium were also isolated from the LAAs soil samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23416228", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 70, "text": " Geobacter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23038171", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 50, "text": "Geobacteraceae", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11976101", "endSection": "title" }, { "offsetInBeginSection": 2262, "offsetInEndSection": 2390, "text": "Geobacteraceae will be responsible for much of the Fe(III) and U(VI) reduction during uranium bioremediation in these sediments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11976101", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 845, "text": " Our previous studies have demonstrated that the microbial communities involved in uranium bioremediation and energy harvesting are both dominated by microorganisms in the family Geobacteraceae and that the organisms in this family are responsible for uranium bioremediation and electron transfer to electrodes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12626092", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 301, "text": "the organisms in the family Geobacteraceae that have been found to be associated with metal reduction in previous studies ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12788780", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1560, "text": "to stimulate the activity of Geobacter species during in situ uranium bioremediation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15819846", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1188, "text": "Geobacteraceae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16204552", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 530, "text": " Geobacter species are known to be important members of the microbial community: (1) a uranium-contaminated aquifer located in Rifle, CO, USA undergoing in situ bioremediation;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18059491", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1069, "text": "Geobacteraceae feoB transcripts in groundwater samples from a site undergoing in situ uranium bioremediation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18279349", "endSection": "abstract" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1635, "text": " Geobacteraceae activity during metal reduction in carbon-amended microcosms, with the highest expression observed in the glucose treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18378664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Geobacter uraniireducens sp. nov., isolated from subsurface sediment undergoing uranium bioremediation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450691", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "A Gram-negative, rod-shaped, motile bacterium, strain Rf4T, which conserves energy from dissimilatory Fe(III) reduction concomitant with acetate oxidation, was isolated from subsurface sediment undergoing uranium bioremediation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450691", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1028, "text": ". Constant levels of Geobacter ompB transcripts were detected in groundwater during a field experiment in which acetate was added to the subsurface to promote in situ uranium bioremediation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18451051", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 280, "text": "Geobacter species are the predominant organisms, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18497157", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1356, "text": "Firmicutes were the predominant organisms whereas no Firmicutes sequences were detected in background sediments which did not have the capacity to sorb U(VI),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18497157", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 350, "text": "Geobacter species that predominates during in situ uranium bioremediation at this site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18843300", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "As part of an effort to diagnose the physiological status of Geobacter species during in situ bioremediation of uranium-contaminated groundwater, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19129865", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 593, "text": "Geobacter uraniireducens", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19129865", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 541, "text": " Geobacter species are often the dominant members of the groundwater community during active bioremediation and the primary organisms catalysing U(VI) reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21261921", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 291, "text": "Anaeromyxobacter dehalogenans strains implicated in hexavalent uranium reduction and immobilization are present in the fractured saprolite subsurface environment at the U.S. Department of Energy Integrated Field-Scale Subsurface Research Challenge (IFC) site near Oak Ridge, TN. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19346346", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 604, "text": "Both enrichments were capable of reducing U(VI) rapidly. 16S rRNA gene clone libraries of the two enrichments revealed that Desulfovibrio spp. are dominant in the sulfate-reducing enrichment, and Clostridium spp. are dominant in the iron-reducing enrichment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19651424", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1373, "text": ". The results demonstrate that Geobacter species can effectively reduce U(VI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Uranium biomineralization by a metal-resistant Pseudomonas aeruginosa strain isolated from uranium mine waste was characterized for its potential in bioremediation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Uranium biomineralization by a metal resistant Pseudomonas aeruginosa strain isolated from contaminated mine waste.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112694", "endSection": "title" }, { "offsetInBeginSection": 358, "offsetInEndSection": 402, "text": "Geobacter-mediated bioremediation of uranium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21337330", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 835, "text": "The cytochrome genes detected were primarily from Geobacter sp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22327592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Acetate amendment at uranium contaminated sites in Rifle, CO. leads to an initial bloom of Geobacter accompanied by the removal of U(VI) from the groundwater, followed by an increase of sulfate-reducing bacteria (SRBs) which are poor reducers of U(VI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22510989", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 271, "text": "Whole-genome microarray analyses of a subsurface isolate of Geobacter uraniireducens,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23275510", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 389, "text": " At the US Department of Energy's Integrated Field Research Challenge (IFRC) site in Rifle, CO, the stimulation of Geobacter growth and activity via subsurface acetate addition leads to precipitation of U(VI) from groundwater as U(IV)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21255372", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 442, "text": "Here, we report a proteomics-based approach for simultaneously documenting the strain membership and microbial physiology of the dominant Geobacter community members during in situ acetate amendment of the U-contaminated Rifle,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19717633", "endSection": "abstract" } ] }, { "body": "How much should be the duration of the QT interval in patients with short QT syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16265378", "http://www.ncbi.nlm.nih.gov/pubmed/17497253", "http://www.ncbi.nlm.nih.gov/pubmed/15890322", "http://www.ncbi.nlm.nih.gov/pubmed/15569843", "http://www.ncbi.nlm.nih.gov/pubmed/16482041", "http://www.ncbi.nlm.nih.gov/pubmed/17432514", "http://www.ncbi.nlm.nih.gov/pubmed/16255754", "http://www.ncbi.nlm.nih.gov/pubmed/19829181" ], "ideal_answer": [ "The short-QT syndrome is characterized by QT intervals <300-330 msec" ], "exact_answer": [ "below 300-330 msec" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060373", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060307", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "factoid", "id": "52fb7c512059c6d71c000069", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "The short QT syndrome constitutes a new clinical entity that is associated with a high incidence of sudden cardiac death, syncope, and/or atrial fibrillation even in young patients and newborns. Patients with this congenital electrical abnormality are characterized by rate-corrected QT intervals<320 ms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15890322", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1294, "text": "QT interval is shortened when QTc is less than 350 ms (1st degree of shortening). In children with QTc below 330 ms (2nd degree of shortening) short QT syndrome should be excluded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16482041", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 183, "text": "The short-QT syndrome is a new clinical entity characterized by corrected QT intervals <300 ms and a high incidence of ventricular tachycardia (VT) and fibrillation (VF). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15569843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Short QT syndrome is a newly described cardiologic entity which associates a short OT interval (QT and QTc < or = 300 ms) on the surface ECG to a high risk of syncope or sudden death due to malignant ventricular arrhythmia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17432514", "endSection": "abstract" } ] }, { "body": "What is known about potential implication of thyroid hormone receptors in arterial hypertension?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11172625", "http://www.ncbi.nlm.nih.gov/pubmed/22068246", "http://www.ncbi.nlm.nih.gov/pubmed/15611830", "http://www.ncbi.nlm.nih.gov/pubmed/8070428", "http://www.ncbi.nlm.nih.gov/pubmed/15701601", "http://www.ncbi.nlm.nih.gov/pubmed/21654857", "http://www.ncbi.nlm.nih.gov/pubmed/23257356", "http://www.ncbi.nlm.nih.gov/pubmed/22837855" ], "ideal_answer": [ "thyroid hormone receptors are implicated in arterial hypertension", "An associations between the THRA rs939348 polymorphism and systolic BP and the risk of hypertension has been observed\nThe levels of the three thyroid hormone receptors isoforms do not differ significantly between spontaneous hypertensive rats and control rats of the same age, either in the left or in the right ventricle.\nThe published results are still unconclusive." ], "concepts": [ "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.disease-ontology.org/api/metadata/DOID:10763", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006973", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011989", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ], "type": "summary", "id": "52f65f372059c6d71c000027", "snippets": [ { "offsetInBeginSection": 1346, "offsetInEndSection": 1605, "text": "For the first time, our study showed associations between the THRA rs939348 polymorphism and systolic BP and the risk of hypertension but not with CHD, although we admit that the statistical power available to study any relationship with CHD was very limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21654857", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1226, "text": "The results of Western blot analyses showed that the levels of the three TR isoforms do not differ significantly between SHRs and control rats of the same age, either in the left or in the right ventricle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11172625", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of abiraterone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21860772", "http://www.ncbi.nlm.nih.gov/pubmed/9876107", "http://www.ncbi.nlm.nih.gov/pubmed/23199349", "http://www.ncbi.nlm.nih.gov/pubmed/22291466", "http://www.ncbi.nlm.nih.gov/pubmed/22672122", "http://www.ncbi.nlm.nih.gov/pubmed/23344012" ], "ideal_answer": [ "Abiraterone acts by inhibiting cytochrome P450 17\u03b1-hydroxylase (CYP17A1), a critical step in androgen biosynthesis, thus leading to inhibition of androgen biosynthesis." ], "concepts": [ "http://www.biosemantics.org/jochem#4266316", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504" ], "type": "summary", "id": "5148b466d24251bc05000037", "snippets": [ { "offsetInBeginSection": 664, "offsetInEndSection": 897, "text": "The recognition of sustained androgen dependence of CRPC has led to the identification of more potent and selective inhibitors of androgen synthesis and androgen-receptor signaling, such as abiraterone and enzalutamide, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23344012", "endSection": "sections.0" }, { "offsetInBeginSection": 566, "offsetInEndSection": 743, "text": "This review summarizes the rationale, mechanism of action and relevant clinical data of abiraterone acetate , an oral androgen biosynthesis inhibitor, in the management of CRPC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23199349", "endSection": "sections.0" }, { "offsetInBeginSection": 350, "offsetInEndSection": 637, "text": "Sipuleucel-T, an immunotherapeutic vaccine, is now available in the US for patients with non-metastatic CRPC and abiraterone, an oral enzyme inhibitor of androgen biosynthesis, as well as cabazitaxel, a cytotoxic chemotherapeutic, have been approved for the treatment of metastatic CRPC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22672122", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Abiraterone (17-(3-pyridyl)androsta-5,16-dien-3beta-ol, 1) is a potent inhibitor (IC50 4 nM for hydroxylase) of human cytochrome P45017alpha.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9876107", "endSection": "sections.0" } ] }, { "body": "The protein neprilysin has an positive effect on Alzheimer disease, how can it be delivered to the brain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23378928", "http://www.ncbi.nlm.nih.gov/pubmed/22751177", "http://www.ncbi.nlm.nih.gov/pubmed/20817034", "http://www.ncbi.nlm.nih.gov/pubmed/17760499", "http://www.ncbi.nlm.nih.gov/pubmed/22114052", "http://www.ncbi.nlm.nih.gov/pubmed/21304989", "http://www.ncbi.nlm.nih.gov/pubmed/23503602", "http://www.ncbi.nlm.nih.gov/pubmed/19469700" ], "ideal_answer": [ "The protein neprilysin can be deliverered to the brain (crossing the blood brain barrier) through: gene tranfer, transgenesis, gene induction, ex-vivo gene therapy, intracardiac (peripheral) administration of viral neprilysin construct, syringe-focused ultrasound device, convection-enhanced delivery and the use of human adipose tissue-derived mesenchymal stem cells that secrete functional neprilysin-bound exosomes" ], "exact_answer": [ [ "Gene transfer with viral vectors" ], [ "Gene transfer with non-viral vectors" ], [ "Transgenesis" ], [ "Gene Induction" ], [ "Fusion of the Apolipoprotein B (ApoB) low-density lipoprotein (LDL) receptor-binding domain to a targeted protein" ], [ "ex vivo gene therapy" ], [ "Intracardiac (peripheral) administration of viral neprilysin construct" ], [ "Syringe-focused ultrasound device" ], [ "Convection-enhanced delivery" ], [ "Use of human adipose tissue-derived mesenchymal stem cells that secrete functional neprilysin-bound exosomes" ] ], "concepts": [ "http://www.uniprot.org/uniprot/NEP_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016503", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018014", "http://www.uniprot.org/uniprot/NEP_RABIT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015260", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023582", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "list", "id": "5162e44f298dcd4e5100004a", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 816, "text": "he novel, syringe-focused US device was used to introduce purified plasmid DNA encoding human neprilysin (hNEP) into mouse hindlimb skeletal muscle concurrent with US protocol", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22114052", "endSection": "sections.0" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1673, "text": "This technique provides a safe and efficient non-viral method for in vivo gene delivery with potential applications in both basic research and in gene therapy of neuronal disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20817034", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "A novel system for in vivo neprilysin gene delivery using a syringe electrode.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20817034", "endSection": "title" }, { "offsetInBeginSection": 97, "offsetInEndSection": 257, "text": "Previous studies have demonstrated the therapeutic potential of viral vector-mediated neprilysin (NEP) gene therapy in mouse models of Alzheimer's disease (AD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22751177", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Convection-enhanced delivery of neprilysin: a novel amyloid-\u03b2-degrading therapeutic strategy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22751177", "endSection": "title" } ] }, { "body": "Which species of bacteria did the mitochondria originate from?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16157484", "http://www.ncbi.nlm.nih.gov/pubmed/9823893", "http://www.ncbi.nlm.nih.gov/pubmed/21217797", "http://www.ncbi.nlm.nih.gov/pubmed/16381962", "http://www.ncbi.nlm.nih.gov/pubmed/11508688", "http://www.ncbi.nlm.nih.gov/pubmed/21300273", "http://www.ncbi.nlm.nih.gov/pubmed/9711305", "http://www.ncbi.nlm.nih.gov/pubmed/17251118", "http://www.ncbi.nlm.nih.gov/pubmed/12594925", "http://www.ncbi.nlm.nih.gov/pubmed/16822756", "http://www.ncbi.nlm.nih.gov/pubmed/10376009" ], "ideal_answer": [ "Biologists agree that the ancestor of mitochondria was an alpha-proteobacterium. Although the Alphaproteobacteria are thought to be the closest relatives of the mitochondrial progenitor, there is dispute as to what its particular sister group is. Accumulating evolutionary data point to a monophyletic origin of mitochondria from the order Rickettsiales. Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondria than is any other microbe studied so far." ], "exact_answer": [ "Biologists agree that the ancestor of mitochondria was an alpha-proteobacterium." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0005739", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001419", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008928" ], "type": "factoid", "id": "56c58f1b5795f9a73e000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Recently, \u03b1-proteobacteria have been shown to possess virus-like gene transfer agents that facilitate high frequency gene transfer in natural environments between distantly related lineages. This system could have driven the genomic integration of the mitochondrial progenitor and its proto-eukaryote host and contributed to the evolutionary mosaic of genes seen in modern-day prokaryotic and eukaryotic genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300273", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 245, "text": "Although the Alphaproteobacteria are thought to be the closest relatives of the mitochondrial progenitor, there is dispute as to what its particular sister group is.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217797", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1440, "text": "More detailed phylogenetic analyses with additional Alphaproteobacteria and including genes from the mitochondria of Reclinomonas americana found matches of mitochondrial genes to those of members of the Rickettsiaceae, Anaplasmataceae, and Rhodospirillaceae families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Biologists agree that the ancestor of mitochondria was an alpha-proteobacterium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17251118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Mitochondria originated by permanent enslavement of purple non-sulphur bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16822756", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 339, "text": "Phylogenetic analyses based on genes located in the mitochondrial genome indicate that these genes originated from within the alpha-proteobacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12594925", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1393, "text": "The strong relationship with alpha-proteobacterial genes observed for some mitochondrial genes, combined with the lack of such a relationship for others, indicates that the modern mitochondrial proteome is the product of both reductive and expansive processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12594925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Accumulating evolutionary data point to a monophyletic origin of mitochondria from the order Rickettsiales.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11508688", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 511, "text": "Evolutionary analyses of proteins encoded in the genome contain the strongest phylogenetic evidence to date for the view that mitochondria descend from alpha-proteobacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10376009", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 551, "text": "The functional profiles of these genes show similarities to those of mitochondrial genes: no genes required for anaerobic glycolysis are found in either R. prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in R. prowazekii.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9823893", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1250, "text": "Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondria than is any other microbe studied so far.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9823893", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 464, "text": "The phylogenetic analysis supports the hypothesis that mitochondria are derived from the alpha-proteobacteria and more specifically from within the Rickettsiaceae. We have estimated that the common ancestor of mitochondria and Rickettsiaceae dates back to more than 1500 million years ago.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9711305", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 665, "text": "GOBASE also includes a fully reannotated genome sequence of Rickettsia prowazekii, one of the closest bacterial relatives of mitochondria, and will shortly expand to contain more data from bacteria from which organelles originated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16381962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The genome sequence of Rickettsia prowazekii and the origin of mitochondria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9823893", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Although mitochondria derive from alpha-proteobacteria, many proteins acting in this organelle did not originate from bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16157484", "endSection": "abstract" } ] }, { "body": "Which disease is linked to mutations within BRAG1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22915114" ], "ideal_answer": [ "Mutations in BRAG1 have been identified in families with X-linked intellectual disability (XLID)." ], "exact_answer": [ "X-linked intellectual disability" ], "type": "factoid", "id": "56f7fe3709dd18d46b000015", "snippets": [ { "offsetInBeginSection": 444, "offsetInEndSection": 540, "text": "Mutations in BRAG1 have been identified in families with X-linked intellectual disability (XLID)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22915114", "endSection": "abstract" } ] }, { "body": "Which is the main calcium pump of the sarcoplasmic reticulum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25531267", "http://www.ncbi.nlm.nih.gov/pubmed/24807223", "http://www.ncbi.nlm.nih.gov/pubmed/24170972", "http://www.ncbi.nlm.nih.gov/pubmed/22482463", "http://www.ncbi.nlm.nih.gov/pubmed/21674635", "http://www.ncbi.nlm.nih.gov/pubmed/24164241", "http://www.ncbi.nlm.nih.gov/pubmed/17584678", "http://www.ncbi.nlm.nih.gov/pubmed/22821874" ], "ideal_answer": [ "Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium homeostasis. SERCA is a membrane protein that belongs to the family of P-type ion translocating ATPases and pumps free cytosolic calcium into intracellular stores." ], "exact_answer": [ "Sarcoplasmic reticulum Ca(2+)-ATPase", "SERCA", "serca2" ], "concepts": [ "http://www.uniprot.org/uniprot/ATC1_DROPS", "http://www.uniprot.org/uniprot/ATC1_DROME", "http://www.uniprot.org/uniprot/ATC1_ANOGA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005388", "http://www.uniprot.org/uniprot/ATC_ARTSF", "http://www.uniprot.org/uniprot/ATCL_BACSU" ], "type": "factoid", "id": "54db62a3034aea571d000001", "snippets": [ { "offsetInBeginSection": 47, "offsetInEndSection": 95, "text": "sarcoplasmic reticulum (SR) calcium pump (SERCA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531267", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 454, "text": "the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24807223", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 609, "text": "SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24807223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium homeostasis and its impairment results in pathologies such as myopathy, heart failure or diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170972", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 454, "text": "Sarcoplasmic reticulum calcium ATPase (SERCA2a), the sarcoplasmic reticulum calcium pump, was found to be a key factor in the alteration of calcium cycling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24164241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays a central role in cardiac contraction, shows decreased expression in heart failure (HF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22482463", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 341, "text": "Calcium is actively accumulated in the endoplasmic reticulum by Sarco/Endoplasmic Reticulum Calcium transport ATPases (SERCA enzymes).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21674635", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 110, "text": "sarco(endo)plasmic reticulum calcium pump (SERCA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584678", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 301, "text": "SERCA is a membrane protein that belongs to the family of P-type ion translocating ATPases and pumps free cytosolic calcium into intracellular stores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584678", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 614, "text": "Three different SERCA genes were identified-SERCA1, SERCA2, and SERCA3. SERCA is mainly represented by the SERCA2a isoform in the heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The sarcoplasmic reticulum Ca\ufffdz ATPase (SERCA) is a membrane-bound pump that utilizes ATP to drive calcium ions from the myocyte cytosol against the higher calcium concentration in the sarcoplasmic reticulum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821874", "endSection": "abstract" } ] }, { "body": "What is the inheritance pattern of Hunter disease or mucopolysaccharidosis II?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3100113", "http://www.ncbi.nlm.nih.gov/pubmed/2112988", "http://www.ncbi.nlm.nih.gov/pubmed/409284", "http://www.ncbi.nlm.nih.gov/pubmed/7904121", "http://www.ncbi.nlm.nih.gov/pubmed/7492964", "http://www.ncbi.nlm.nih.gov/pubmed/6418001", "http://www.ncbi.nlm.nih.gov/pubmed/20509947" ], "ideal_answer": [ "X- linked recessive" ], "exact_answer": [ "X- linked recessive" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.disease-ontology.org/api/metadata/DOID:12799", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016532", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050172" ], "type": "factoid", "id": "5344155faeec6fbd07000005", "snippets": [ { "offsetInBeginSection": 6, "offsetInEndSection": 182, "text": "ysosomal diseases (LD) are inherited as autosomal recessive traits, but two important conditions have X-linked inheritance: Fabry disease and Mucopolysaccharidosis II (MPS II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20509947", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 98, "text": "unter disease, Mucopolysaccharidosis type II, is an X-linked recessive lysosomal storage disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7492964", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 49, "text": "unter syndrome is an X-linked recessive disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7904121", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1265, "text": "X chromosome heterozygosity and confirmed the paternal origin of one of the X chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2112988", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 77, "text": " Hunter's disease in a female with an X-chromosome deletion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3100113", "endSection": "title" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1107, "text": "Chromosome studies on the patient revealed a partial deletion of the long arm of one X-chromosome,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3100113", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 44, "text": "unter disease, an X-linked recessive lethal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6418001", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 358, "text": "X-linked disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/409284", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 30, "text": "Hunter syndrome in females", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/409284", "endSection": "title" } ] }, { "body": "Do ephrins play a role in brain cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18794797", "http://www.ncbi.nlm.nih.gov/pubmed/16254188", "http://www.ncbi.nlm.nih.gov/pubmed/23686814", "http://www.ncbi.nlm.nih.gov/pubmed/18366728", "http://www.ncbi.nlm.nih.gov/pubmed/15126357", "http://www.ncbi.nlm.nih.gov/pubmed/15473927", "http://www.ncbi.nlm.nih.gov/pubmed/19728339", "http://www.ncbi.nlm.nih.gov/pubmed/16951161", "http://www.ncbi.nlm.nih.gov/pubmed/20571968", "http://www.ncbi.nlm.nih.gov/pubmed/19270726", "http://www.ncbi.nlm.nih.gov/pubmed/22723427", "http://www.ncbi.nlm.nih.gov/pubmed/19074825", "http://www.ncbi.nlm.nih.gov/pubmed/22688511", "http://www.ncbi.nlm.nih.gov/pubmed/14726470", "http://www.ncbi.nlm.nih.gov/pubmed/10984508", "http://www.ncbi.nlm.nih.gov/pubmed/18089715", "http://www.ncbi.nlm.nih.gov/pubmed/22374425", "http://www.ncbi.nlm.nih.gov/pubmed/17332925" ], "ideal_answer": [ "Eph receptors and ephrin ligands are involved in the development of the central nervous system. Their expression is often reported to be up-regulated in brain tumours and they may be considered molecular markers for the diagnosis of invasive and metastatic tumours. However, there are also reports describing the down-regulation of the Eph/ephrin family in brain cancer." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D036342", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.disease-ontology.org/api/metadata/DOID:1319", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046875" ], "type": "summary", "id": "53442472aeec6fbd07000008", "snippets": [ { "offsetInBeginSection": 1504, "offsetInEndSection": 1745, "text": "migrating glioblastoma cells overexpress EphB2 in vitro and in vivo; glioma migration and invasion are promoted by activation of EphB2 or inhibited by blocking EphB2. Dysregulation of EphB2 expression or function may underlie glioma invasion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15126357", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 93, "text": "gene expression of Eph receptors and ephrins in benign human tissues and cancers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14726470", "endSection": "title" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1175, "text": "EphA1/EphA8 was down-regulated in glioblastomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14726470", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 75, "text": "EPHB6, EFNB2, and EFNB3 expressions in human neuroblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10984508", "endSection": "title" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1724, "text": "high-level expressions of favorable NB genes, such as EPHB6, can in fact suppress malignant phenotype of unfavorable NB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10984508", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 117, "text": "phrin-As, Eph receptors and integrin \u03b13 interact and colocalise at membrane protrusions of U251MG glioblastoma cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686814", "endSection": "title" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1256, "text": "crosstalk between Eph and integrin signalling pathways at the membrane protrusions and in the migration of brain cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686814", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 91, "text": "phB2 activity plays a pivotal role in pediatric medulloblastoma cell adhesion and invasion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723427", "endSection": "title" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1474, "text": "deregulation of Eph/ephrin expression in medulloblastoma enhances the invasive phenotype, suggesting a potential role in local tumor cell invasion and the formation of metastases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723427", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 53, "text": "phrinA1 is released in three forms from cancer cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22688511", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 152, "text": "phrinA1 is a glycosylphosphatidylinositol (GPI)-linked ligand for the EphA2 receptor, which is overexpressed in glioblastoma (GBM), among other cancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22688511", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 133, "text": "EphrinB2 and EphB4 in glioma tissues correlated to the progression of glioma and the prognosis of glioblastoma patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374425", "endSection": "title" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1621, "text": "EphrinB2 and EphB4 expressions increase according to the histopathological grade and KPS score of glioma, and their expression levels are related to the progression-free survival of glioblastoma patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374425", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 138, "text": "p-regulation of EphA2 and down-regulation of EphrinA1 are associated with the aggressive phenotype and poor prognosis of malignant glioma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20571968", "endSection": "title" }, { "offsetInBeginSection": 10, "offsetInEndSection": 81, "text": "gliomas display over-expression of the receptor tyrosine kinase EphA2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20571968", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 83, "text": "phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728339", "endSection": "title" }, { "offsetInBeginSection": 1624, "offsetInEndSection": 1824, "text": "high expression of ephrin-B2 is a strong predictor of short-term survival and that ephrin-B2 plays a critical role in glioma invasion rendering this signaling pathway as a potential therapeutic target", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728339", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 45, "text": "phrinA5 acts as a tumor suppressor in glioma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270726", "endSection": "title" }, { "offsetInBeginSection": 253, "offsetInEndSection": 354, "text": "expression of ephrinA5 was dramatically downregulated in primary gliomas compared with normal tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270726", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 54, "text": "EphA2 receptor and ephrinA1 ligand in solid tumors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074825", "endSection": "title" }, { "offsetInBeginSection": 228, "offsetInEndSection": 414, "text": "investigating the ephrinA1/EphA2 system in the pathobiology of glioblastoma multiforme (GBM), we uncovered that ephrinA1 is released from GBM and breast adenocarcinoma cells as a soluble", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18794797", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 569, "text": "ccumulating evidence indicates that Eph and ephrins are frequently overexpressed in different tumor types including GBM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18366728", "endSection": "abstract" }, { "offsetInBeginSection": 34, "offsetInEndSection": 201, "text": "EphA2 receptor tyrosine kinase is overexpressed in glioblastoma multiforme (GBM) and represents a novel, attractive therapeutic target for the treatment of brain tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18089715", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 43, "text": "phrin-A1 is a negative regulator in glioma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17332925", "endSection": "title" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1059, "text": " ephrin-A1 serves as a critical negative regulator in the tumorigenesis of gliomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17332925", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 338, "text": "overexpression of EphB2 in glioma cells increases cell invasion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951161", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 71, "text": "phA2 as a novel molecular marker and target in glioblastoma multiforme", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254188", "endSection": "title" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1240, "text": "EphA2 is both specifically overexpressed in GBM and expressed differentially with respect to its ligand, ephrinA1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254188", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 300, "text": "EphB4 and EphrinB2 protein expression in astrocytomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15473927", "endSection": "abstract" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1242, "text": "Expressions of EphB4 and EphrinB2 proteins may be related to differentiation degree of tumor cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15473927", "endSection": "abstract" } ] }, { "body": "What is the effect of the absence of Saccharomyces cerevisiae Rrm3p?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18725402", "http://www.ncbi.nlm.nih.gov/pubmed/12050116", "http://www.ncbi.nlm.nih.gov/pubmed/14690605", "http://www.ncbi.nlm.nih.gov/pubmed/19277716", "http://www.ncbi.nlm.nih.gov/pubmed/16418273", "http://www.ncbi.nlm.nih.gov/pubmed/19560424", "http://www.ncbi.nlm.nih.gov/pubmed/15037547", "http://www.ncbi.nlm.nih.gov/pubmed/19414561", "http://www.ncbi.nlm.nih.gov/pubmed/21087929", "http://www.ncbi.nlm.nih.gov/pubmed/15060144" ], "ideal_answer": [ "The Saccharomyces cerevisiae RRM3 gene encodes a 5' to 3' DNA helicase. While replication of most of the yeast genome was not dependent upon Rrm3p, in its absence, replication forks paused and often broke at an estimated 1400 discrete sites, including tRNA genes, centromeres, inactive replication origins, and transcriptional silencers. These replication defects were associated with activation of the intra-S phase checkpoint. Activation of the checkpoint was critical for viability of rrm3Delta cells, especially at low temperatures.", "The Saccharomyces cerevisiae RRM3 gene encodes a 5 to 3 DNA helicase. While replication of most of the yeast genome was not dependent upon Rrm3p, in its absence, replication forks paused and often broke at an estimated 1400 discrete sites, including tRNA genes, centromeres, inactive replication origins, and transcriptional silencers. These replication defects were associated with activation of the intra-S phase checkpoint. Activation of the checkpoint was critical for viability of rrm3Delta cells, especially at low temperatures " ], "exact_answer": [ "Lack of the yeast Rrm3p DNA helicase causes replication defects at multiple sites within ribosomal DNA (rDNA), including at the replication fork barrier (RFB)." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012441" ], "type": "factoid", "id": "553ca8d8f32186855800000d", "snippets": [ { "offsetInBeginSection": 585, "offsetInEndSection": 929, "text": "Twice as many pause sites were identified in rrm3 compared with wild-type cells, as pausing in this strain occurred at both highly transcribed RNA polymerase II genes and the previously identified protein DNA complexes. ORFs of highly transcribed RNA polymerase II genes are a class of natural pause sites that are not exacerbated in rrm3 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19560424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "The DNA helicase Rrm3 promotes replication fork progression through >1000 discrete genomic regions and represses the cDNA-mediated mobility of the Ty1 retrotransposon. We explored the connection between DNA replication and Ty1 retromobility by investigating the basis of increased retromobility in an rrm3 mutant. Even though Ty1 cDNA levels are increased in the absence of RRM3, neither the level nor target-site specificity of cDNA integration was altered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19414561", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1261, "text": "We propose that RNA:DNA hybrid regions within nascent retrotransposition events block replication in an rrm3 mutant, leading to chromosome breaks within Ty1 sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19414561", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 447, "text": "We demonstrate that the inefficient mtDNA replication process of mutant yeast cells lacking the PIF1 DNA helicase is partly rescued in the absence of the DNA helicase RRM3. The rescue effect is likely due to the increase in the deoxynucleoside triphosphates (dNTPs) pool caused by the lack of RRM3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19277716", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1309, "text": " However, the essential nuclear function of Pfh1p could be supplied by Rrm3p. Expression of Rrm3p suppressed the accumulation of DNA damage foci but not the hydroxyurea sensitivity of cells depleted of nuclear Pfh1p. Together, these data demonstrate that Pfh1p has essential roles in the replication of both nuclear and mitochondrial DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18725402", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1100, "text": " In the absence of the Rrm3p helicase, there was a slight enhancement of fork arrest at the Ter sites. Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes restored fork arrest by removing both the fork-releasing and fork-protection activities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16418273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Rrm3p is a 5'-to-3' DNA helicase that helps replication forks traverse protein-DNA complexes. Its absence leads to increased fork stalling and breakage at over 1,000 specific sites located throughout the Saccharomyces cerevisiae genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15060144", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1043, "text": "These data suggest a model in which the stalled and broken forks generated in rrm3 cells activate a checkpoint response that provides time for fork repair and restart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15060144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Lack of the yeast Rrm3p DNA helicase causes replication defects at multiple sites within ribosomal DNA (rDNA), including at the replication fork barrier (RFB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15037547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 535, "text": "The Saccharomyces cerevisiae RRM3 gene encodes a 5' to 3' DNA helicase. While replication of most of the yeast genome was not dependent upon Rrm3p, in its absence, replication forks paused and often broke at an estimated 1400 discrete sites, including tRNA genes, centromeres, inactive replication origins, and transcriptional silencers. These replication defects were associated with activation of the intra-S phase checkpoint. Activation of the checkpoint was critical for viability of rrm3Delta cells, especially at low temperatures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14690605", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 926, "text": "These data indicate that the Rrm3p DNA helicase helps replication forks traverse protein-DNA complexes, naturally occurring impediments that are encountered in each S phase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14690605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "In wild-type Saccharomyces cerevisiae, replication forks slowed during their passage through telomeric C(1-3)A/TG(1-3) tracts. This slowing was greatly exacerbated in the absence of RRM3, shown here to encode a 5' to 3' DNA helicase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12050116", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 579, "text": " Loss of Rrm3p also resulted in replication fork pausing at specific sites in subtelomeric DNA, such as at inactive replication origins, and at internal tracts of C(1-3)A/TG(1-3) DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12050116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15037547", "endSection": "title" } ] }, { "body": "Do all archaea possess multiple origins of DNA replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25309521", "http://www.ncbi.nlm.nih.gov/pubmed/24822028", "http://www.ncbi.nlm.nih.gov/pubmed/24185008", "http://www.ncbi.nlm.nih.gov/pubmed/14718164", "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "http://www.ncbi.nlm.nih.gov/pubmed/15337158", "http://www.ncbi.nlm.nih.gov/pubmed/24808892" ], "ideal_answer": [ "Origins of DNA replication differ in number and structure across the three domains of life and their properties determine the dynamics of chromosome replication. Though most archaea replicate their chromosomes using multiple origins, there are also certain archaea that possess a single origin of DNA replication (such as Pyrococcus abyssi and some archaea belonging in the hyperthermophilic order of Themococcales)." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006260", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003688", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018741" ], "type": "yesno", "id": "5547d72ef35db75526000008", "snippets": [ { "offsetInBeginSection": 151, "offsetInEndSection": 424, "text": "Origins differ in number and structure across the three domains of life and their properties determine the dynamics of chromosome replication. Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185008", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 508, "text": "Replication starts at a single Ori site in bacteria, but in eukaryotes multiple Ori sites are used for fast copying across all chromosomes. The situation becomes complex in archaea, where some groups have single and others have multiple origins of replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1322, "text": "Results from this in silico analysis show that the Themococcales have a single origin of replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Until recently, the only archaeon for which a bona fide origin of replication was reported was Pyrococcus abyssi, where a single origin was identified. Although several in silico analyses have suggested that some archaeal species might contain more than one origin, this has only been demonstrated recently.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15337158", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 445, "text": "In bacteria and eukaryotes, replication initiates from single and multiple origins, respectively, while archaea can adopt either of the two modes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24822028", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 422, "text": "Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185008", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 423, "text": "Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185008", "endSection": "abstract" } ] }, { "body": "What is the ubiquitin proteome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22178446", "http://www.ncbi.nlm.nih.gov/pubmed/23743150", "http://www.ncbi.nlm.nih.gov/pubmed/23764619" ], "ideal_answer": [ "The ubiquitin proteome is the entire set ubiquitinated proteins and of their respective ubiquitination sites." ], "exact_answer": [ "The ubiquitin proteome is the entire set ubiquitinated proteins and of their respective ubiquitination sites." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014452", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054875", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025801", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016567", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031386", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057149", "http://www.uniprot.org/uniprot/UBIQ_CERCA" ], "type": "factoid", "id": "532f1452d6d3ac6a34000030", "snippets": [ { "offsetInBeginSection": 266, "offsetInEndSection": 422, "text": "Mass spectrometry now allows high throughput approaches for the identification of the thousands of ubiquitinated proteins and of their ubiquitination sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23764619", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 543, "text": "we used Tandem repeated Ubiquitin Binding Entities (TUBEs) under non-denaturing conditions followed by mass spectrometry analysis to study global ubiquitylation events that may lead to the identification of potential drug targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22178446", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 339, "text": "To study the ubiquitin proteome we have established an immunoaffinity purification method for the proteomic analysis of endogenously ubiquitinated protein complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23743150", "endSection": "abstract" } ] }, { "body": "Which major signaling pathways are regulated by RIP1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25767797", "http://www.ncbi.nlm.nih.gov/pubmed/24224954", "http://www.ncbi.nlm.nih.gov/pubmed/24460252", "http://www.ncbi.nlm.nih.gov/pubmed/25391899", "http://www.ncbi.nlm.nih.gov/pubmed/23674612", "http://www.ncbi.nlm.nih.gov/pubmed/25326752", "http://www.ncbi.nlm.nih.gov/pubmed/24874734" ], "ideal_answer": [ "necroptosis\napoptosis \npro-survival/inflammation NF-\u03baB activation" ], "exact_answer": [ [ "necroptosis" ], [ "apoptosis" ], [ "pro-survival/inflammation NF-\u03baB activation" ] ], "type": "list", "id": "570a922dcf1c325851000028", "snippets": [ { "offsetInBeginSection": 159, "offsetInEndSection": 282, "text": "Major signaling pathways regulated by RIP1 include necroptosis, apoptosis, and pro-survival/inflammation NF-\u03baB activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25767797", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 924, "text": "receptor-interacting protein-1 (RIP1)-mediated necroptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25391899", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1257, "text": "TNF-induced apoptotic signaling pathways were assessed by monitoring levels of the anti-apoptotic protein, A20, and cleavage products of the caspase-8 substrate, RIP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24224954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24874734", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 946, "text": "Together our results reveal a specific role for the RIP1-RIP3-DRP1 pathway in RNA virus-induced activation of the NLRP3 inflammasome and establish a direct link between inflammation and cell-death signaling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326752", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 545, "text": "Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24460252", "endSection": "abstract" } ] }, { "body": "What is the effect induced by sympathetic nervous system on pupil size?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7697953", "http://www.ncbi.nlm.nih.gov/pubmed/3423165", "http://www.ncbi.nlm.nih.gov/pubmed/6881176", "http://www.ncbi.nlm.nih.gov/pubmed/21601076", "http://www.ncbi.nlm.nih.gov/pubmed/14639139", "http://www.ncbi.nlm.nih.gov/pubmed/9357887", "http://www.ncbi.nlm.nih.gov/pubmed/11306012", "http://www.ncbi.nlm.nih.gov/pubmed/7188336", "http://www.ncbi.nlm.nih.gov/pubmed/6413073", "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "http://www.ncbi.nlm.nih.gov/pubmed/3604881", "http://www.ncbi.nlm.nih.gov/pubmed/9247742", "http://www.ncbi.nlm.nih.gov/pubmed/6499637", "http://www.ncbi.nlm.nih.gov/pubmed/1619750" ], "ideal_answer": [ "Pupil size is determined by the interaction of the parasympathetic and the sympathetic nervous system. The sympathetic nervous system acts either directly on the dilator muscle (peripherally) or centrally by inhibiting the Edinger-Westphal nucleus. Thus, the sympathetic nervous system mediates pupillary dilatation." ], "exact_answer": [ "pupillary dilatation (increase of the pupil size)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009420", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018373", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013564", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001342" ], "type": "factoid", "id": "5547ec32f35db7552600000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Pupil size is determined by the interaction of the parasympathetic and the sympathetic nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21601076", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 349, "text": "The sympathetic nervous system acts either directly on the dilator muscle (peripherally) or centrally by inhibiting the Edinger-Westphal nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21601076", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 285, "text": "The mechanism of reflex pupillary dilation was investigated in eight patients who were declared brain dead after rupture of intracranial vascular malformations and in eight awake volunteers. The authors hypothesized that the reflex was primarily a spinal sympathetic reflex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14639139", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1704, "text": "The authors conclude that pupillary reflex dilation, as it is clinically performed in awake subjects by stimulating somatic nociceptors, is a sympathetic reflex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14639139", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1155, "text": "Sympathetic nervous system activation, with reflex dilation of the pupil", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1465, "text": "reproducibly larger pupil size--indicative of increased sympathetic arousal--", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3604881", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 729, "text": "activation of autonomic sympathetic preganglionic neurons in the thoracic spinal cord produces pupillary dilatation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11306012", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 661, "text": "sympathetic responses (sweating, pupil dilatation, piloerection, etc.)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9247742", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 323, "text": "In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1277, "text": "Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane, and by a rapid 4%-to-8% step-up in the desflurane concentration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "BACKGROUND: Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1115, "text": "Dark-adapted pupil size after topical PNS blockade (an index of iris sympathetic nervous system [SNS] activity) was also smaller in both groups of diabetic subjects (NIDD, P less than 0.01; IDD, P less than 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6499637", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1408, "text": "However, dark-adapted pupil size during parasympathetic nervous system blockade, an index of iris sympathetic nervous system activity, declined with age (r = -0.81, p less than 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6881176", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1407, "text": "However, dark-adapted pupil size during parasympathetic nervous system blockade, an index of iris sympathetic nervous system activity, declined with age (r = -0.81, p less than 0.001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6881176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Pupil size is determined by the interaction of the parasympathetic and the sympathetic nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21601076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873544", "endSection": "abstract" } ] }, { "body": "Is p100 the precursor protein molecule of the NF-kappaB transcription factor subunit p50?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11158290", "http://www.ncbi.nlm.nih.gov/pubmed/12505990", "http://www.ncbi.nlm.nih.gov/pubmed/15677466", "http://www.ncbi.nlm.nih.gov/pubmed/12894228", "http://www.ncbi.nlm.nih.gov/pubmed/16223731", "http://www.ncbi.nlm.nih.gov/pubmed/17693123", "http://www.ncbi.nlm.nih.gov/pubmed/20363924", "http://www.ncbi.nlm.nih.gov/pubmed/12556537", "http://www.ncbi.nlm.nih.gov/pubmed/22282470", "http://www.ncbi.nlm.nih.gov/pubmed/8649779", "http://www.ncbi.nlm.nih.gov/pubmed/19302050", "http://www.ncbi.nlm.nih.gov/pubmed/8398903", "http://www.ncbi.nlm.nih.gov/pubmed/10207090", "http://www.ncbi.nlm.nih.gov/pubmed/13679070", "http://www.ncbi.nlm.nih.gov/pubmed/10597218", "http://www.ncbi.nlm.nih.gov/pubmed/15485830", "http://www.ncbi.nlm.nih.gov/pubmed/11726516", "http://www.ncbi.nlm.nih.gov/pubmed/8710364" ], "ideal_answer": [ "No, the precursor molecule for NF-kappaB p50 is p105 and not p100. Nfkb2 encodes two members of the NF-kappa B/Rel family of proteins: p52 and p100. The p100 polypeptide has been proposed to serve as a precursor of p52 (and not of p50), which corresponds to the N-terminal half of p100. NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel." ], "exact_answer": "no", "type": "yesno", "id": "55088e412e93f0133a000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "We previously reported that alymphoplasia (aly/aly) mice, which have a natural loss-of-function mutation in the Nik gene, which encodes a kinase essential for the processing of p100 to p52 in the alternative nuclear factor-\u03baB (NF-\u03baB) pathway, show mild osteopetrosis with an increase in several parameters of bone formation: ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22282470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Proteolytic processing of the nuclear factor (NF)-kappaB2 precursor protein p100 generates the active NF-kappaB2 subunit p52, which in turn transcriptionally up-regulates p100 expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20363924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 391, "text": "The mammalian Rel/NF-kappaB family of transcription factors, including RelA, c-Rel, RelB, NF-kappaB1 (p50 and its precursor p105), and NF-kappaB2 (p52 and its precursor p100), plays a central role in the immune system by regulating several processes ranging from the development and survival of lymphocytes and lymphoid organs to the control of immune responses and malignant transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19302050", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 334, "text": "NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17693123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The non-canonical pathway based on processing of NF-kappaB2 precursor protein p100 to generate p52 plays a critical role in controlling B cell function and lymphoid organogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16223731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Processing of NF-kappaB2 precursor protein p100 to generate p52 is tightly controlled, which is important for proper function of NF-kappaB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15677466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Processing of NF-kappa B2 precursor protein p100 to generate p52 is tightly regulated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15485830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Processing of the NF-kappaB2 precursor protein p100 to generate p52 is an important step of NF-kappaB regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12894228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Targeted disruption of the Rel/NF-kappaB family members NF-kappaB2, encoding p100/p52, and RelB in mice results in anatomical defects of secondary lymphoid tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12505990", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 541, "text": "Here, we show that in T cells infected with the human T-cell leukemia virus (HTLV), IKKalpha is targeted to a novel signaling pathway that mediates processing of the nfkappab2 precursor protein p100, resulting in active production of the NF-kappaB subunit, p52.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11726516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "nfkb2 encodes two members of the NF-kappa B/Rel family of proteins: p52 and p100. The p100 polypeptide has been proposed to serve as a precursor of p52, which corresponds to the N-terminal half of p100.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10597218", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 985, "text": "In most cells, small amounts of p52 are produced relative to the levels of p100, unlike the usually balanced production of nfkb1-derived p50 and p105. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10597218", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 686, "text": "The alternative or second pathway proceeded via NF-kappaB-inducing kinase (NIK)-, IKKalpha-, and protein synthesis-dependent processing of the inhibitory NF-kappaB2 p100 precursor protein to the p52 form and resulted in a delayed but sustained activation of primarily RelB-containing NF-kappaB dimers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12556537", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 421, "text": "In one exceptional case, generation of the p50 subunit of the transcriptional regulator NF-kappaB, the precursor protein p105 is processed in a limited manner: the N-terminal domain yields the p50 subunit, whereas the C-terminal domain is degraded", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10207090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Proteolytic processing of the p105 precursor (NF-kappa B1) generates the p50 subunit of NF-kappa B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8710364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "p105 (NFKB1) acts in a dual way as a cytoplasmic IkappaB molecule and as the source of the NF-kappaB p50 subunit upon processing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11158290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The p50 subunit of NF-kappa B is derived from the amino terminus of a 105 kilodalton precursor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8398903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Regulation of the transcription factor NF-kappaB involves proteasome-mediated processing of the NF-kappaB1 p105 precursor protein, which generates the p50 subunit of NF-kappaB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8649779", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 518, "text": "This effort identified NF-kappaB1 (p105), an atypical IkappaB molecule and the precursor of NF-kappaB subunit p50", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/13679070", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 333, "text": "NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17693123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 390, "text": "The mammalian Rel/NF-kappaB family of transcription factors, including RelA, c-Rel, RelB, NF-kappaB1 (p50 and its precursor p105), and NF-kappaB2 (p52 and its precursor p100), plays a central role in the immune system by regulating several processes ranging from the development and survival of lymphocytes and lymphoid organs to the control of immune responses and malignant transformation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19302050", "endSection": "abstract" } ] }, { "body": "What is the definition and the biological role of epithelial-mesenchymal transition (EMT)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22844540", "http://www.ncbi.nlm.nih.gov/pubmed/20819124", "http://www.ncbi.nlm.nih.gov/pubmed/24278531", "http://www.ncbi.nlm.nih.gov/pubmed/17922020", "http://www.ncbi.nlm.nih.gov/pubmed/23001200", "http://www.ncbi.nlm.nih.gov/pubmed/23073116", "http://www.ncbi.nlm.nih.gov/pubmed/14644200", "http://www.ncbi.nlm.nih.gov/pubmed/19249648", "http://www.ncbi.nlm.nih.gov/pubmed/24090504" ], "ideal_answer": [ "Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Several oncogenic pathways such as transforming growth factor (TGF) -\u03b2, Wnt, and Notch signaling pathways, have been shown to induce EMT. The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms. This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma.", "This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma. This term is used to describe the mechanisms facilitating cellular repositioning and redeployment during embryonic development and tissue reconstruction after injury. Several oncogenic pathways such as transforming growth factor (TGF) -\u03b2, Wnt, and Notch signaling pathways, have been shown to induce EMT. Recently, EMT has also been applied to potential mechanisms for malignant progression and has appeared as a specific diagnostic category of tumors. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. EMT has also been reported to produce cells with stem cell-like properties. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Epithelial-to-mesenchymal transition (EMT) is a process known to contribute to metastasis in cancer and it is mainly characterized by loss of E-cadherin expression. ", "This term is used to describe the mechanisms facilitating cellular repositioning and redeployment during embryonic development and tissue reconstruction after injury. This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma. Several oncogenic pathways such as transforming growth factor (TGF) -\u03b2, Wnt, and Notch signaling pathways, have been shown to induce EMT. Recently, EMT has also been applied to potential mechanisms for malignant progression and has appeared as a specific diagnostic category of tumors. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. EMT has also been reported to produce cells with stem cell-like properties. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Epithelial-to-mesenchymal transition (EMT) is a process known to contribute to metastasis in cancer and it is mainly characterized by loss of E-cadherin expression. " ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060317", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060231" ], "type": "summary", "id": "55074fa8bde8548216000003", "snippets": [ { "offsetInBeginSection": 547, "offsetInEndSection": 711, "text": "Epithelial-to-mesenchymal transition (EMT) is a process known to contribute to metastasis in cancer and it is mainly characterized by loss of E-cadherin expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090504", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 957, "text": "The TGF-\u03b2 signaling pathway has an established role in promoting EMT by down-regulating E-cadherin via a number of transcription factors, such as Twist, Snail and Slug. EMT has also been reported to produce cells with stem cell-like properties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Epithelial to mesenchymal transition (EMT) has been hypothesized as a mechanism by which cells change phenotype during carcinogenesis, as well as tumor metastasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 532, "text": "Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Several oncogenic pathways such as transforming growth factor (TGF) -\u03b2, Wnt, and Notch signaling pathways, have been shown to induce EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24278531", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 750, "text": "These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24278531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Epithelial-mesenchymal transition (EMT) is suggested to be crucial for the development of an invasive and metastatic carcinoma cell phenotype. Therefore, the definition of this phenotype is of great clinical interest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20819124", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1138, "text": "Recent work has suggested that there may be a linkage between the stem cell phenotype and that induced by the process of epithelial-mesenchymal transition (EMT). EMT plays an important role in cell movement and organ formation during embryogenesis, and it is currently hypothesized to be a major mechanism by which epithelial cancers may generate cells that can form metastases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19249648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "The term EMT (epithelial-mesenchymal transition) is used in many settings. This term is used to describe the mechanisms facilitating cellular repositioning and redeployment during embryonic development and tissue reconstruction after injury. Recently, EMT has also been applied to potential mechanisms for malignant progression and has appeared as a specific diagnostic category of tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17922020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms. This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14644200", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 192, "text": "Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23073116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Epithelial-mesenchymal transition (EMT) is a biological process that drives polarized, immotile epithelial cells to undergo multiple biochemical changes to acquire a mesenchymal cell phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Epithelial-mesenchymal transition (EMT) is a biological process that drives polarized, immotile epithelial cells to undergo multiple biochemical changes to acquire a mesenchymal cell phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001200", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 191, "text": "Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23073116", "endSection": "abstract" } ] }, { "body": "Is there a difference in the rate between gene fusion and gene fission?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16601004", "http://www.ncbi.nlm.nih.gov/pubmed/21729286", "http://www.ncbi.nlm.nih.gov/pubmed/17166515", "http://www.ncbi.nlm.nih.gov/pubmed/22250127", "http://www.ncbi.nlm.nih.gov/pubmed/16431849", "http://www.ncbi.nlm.nih.gov/pubmed/17035354", "http://www.ncbi.nlm.nih.gov/pubmed/21900599", "http://www.ncbi.nlm.nih.gov/pubmed/15680510", "http://www.ncbi.nlm.nih.gov/pubmed/17709334", "http://www.ncbi.nlm.nih.gov/pubmed/23376183", "http://www.ncbi.nlm.nih.gov/pubmed/19141283" ], "ideal_answer": [ "Yes. Several studies have estimated that gene fusion and fission are relatively rare events and the gene fusion/fission rate is approximately between 2 and 6. A conflicting case has been discovered in an analysis of plant genomes, where in Oryza sativa the opposite trend was observed." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050939" ], "type": "yesno", "id": "5149b575d24251bc05000047", "snippets": [ { "offsetInBeginSection": 629, "offsetInEndSection": 860, "text": "we illustrate arrangement diversity within closely related organisms, estimate arrangement turnover frequency and establish, for the first time, branch-specific rate estimates for fusion, fission, domain addition and terminal loss.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376183", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Rate and polarity of gene fusion and fission in Oryza sativa and Arabidopsis thaliana", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035354", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 322, "text": "We have identified all differentially composite or split genes in 2 fully sequenced plant genomes, Oryza sativa and Arabidopsis thaliana", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035354", "endSection": "sections.0" }, { "offsetInBeginSection": 498, "offsetInEndSection": 796, "text": "Polarizing these events by outgroup comparison revealed differences in the rate of gene fission but not of gene fusion in the rice and Arabidopsis lineages. Gene fission occurred at a higher rate than gene fusion in the O. sativa lineage and was furthermore more common in rice than in Arabidopsis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035354", "endSection": "sections.0" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1629, "text": "Gene fusion and fission are thus rare and slow processes in higher plant genomes; they should be of utility to address deeper evolutionary relationships among plants--and the relationship of plants to other eukaryotic lineages--where sequence-based phylogenies provide equivocal or conflicting results.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17035354", "endSection": "sections.0" }, { "offsetInBeginSection": 393, "offsetInEndSection": 677, "text": "Primary factors correlating with fusion rates are the presence of transmembrane helices in HKs and the presence of DNA-binding domains in RRs, features that require correct (and separate) spatial location. In the absence of such features, there is a relative abundance of fused genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17709334", "endSection": "sections.0" }, { "offsetInBeginSection": 576, "offsetInEndSection": 1187, "text": "We show that indels are the most frequent elementary events and that they occur in most cases at either the N- or C-terminus of the proteins. As revealed by the genomic neighbourhood/context of the corresponding genes, we show that a substantial number of these terminal indels are the consequence of gene fusions/fissions. We provide evidence showing that the contribution of gene fusion/fission to the evolution of multi-domain bacterial proteins is lower-bounded by 27% and upper-bounded by 64%. We conclude that gene fusion/fission is a major contributor to the evolution of multi-domain bacterial proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16601004", "endSection": "sections.0" }, { "offsetInBeginSection": 391, "offsetInEndSection": 610, "text": "We found that fusion events are approximately four times more common than fission events, and we established that, in most cases, any particular fusion or fission event only occurred once during the course of evolution.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15680510", "endSection": "sections.0" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1501, "text": "Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17166515", "endSection": "sections.0" }, { "offsetInBeginSection": 392, "offsetInEndSection": 767, "text": "These trees defined timelines of architectural discovery and revealed remarkable evolutionary patterns, including the explosive appearance of domain combinations during the rise of organismal lineages, the dominance of domain fusion processes throughout evolution, and the late appearance of a new class of multifunctional modules in Eukarya by fission of domain combinations", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19141283", "endSection": "sections.0" }, { "offsetInBeginSection": 608, "offsetInEndSection": 899, "text": "We searched for examples which have arisen by one of the three postulated mechanisms: independent fusion/fission, \"duplication/deletion,\" and plasmid-mediated \"cut and paste.\" We conclude that all three mechanisms can be observed, with the independent fusion/fission being the most frequent.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16431849", "endSection": "sections.0" } ] }, { "body": "What type of cancers and inherited diseases have been associated to mutations in the Notch pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9585603", "http://www.ncbi.nlm.nih.gov/pubmed/16773578", "http://www.ncbi.nlm.nih.gov/pubmed/17584081", "http://www.ncbi.nlm.nih.gov/pubmed/19289631", "http://www.ncbi.nlm.nih.gov/pubmed/21562564", "http://www.ncbi.nlm.nih.gov/pubmed/11180599", "http://www.ncbi.nlm.nih.gov/pubmed/22488849", "http://www.ncbi.nlm.nih.gov/pubmed/9207788", "http://www.ncbi.nlm.nih.gov/pubmed/18775957", "http://www.ncbi.nlm.nih.gov/pubmed/23095891", "http://www.ncbi.nlm.nih.gov/pubmed/12497640", "http://www.ncbi.nlm.nih.gov/pubmed/20087400", "http://www.ncbi.nlm.nih.gov/pubmed/20823234", "http://www.ncbi.nlm.nih.gov/pubmed/22156581", "http://www.ncbi.nlm.nih.gov/pubmed/23359070", "http://www.ncbi.nlm.nih.gov/pubmed/22891273", "http://www.ncbi.nlm.nih.gov/pubmed/15712272", "http://www.ncbi.nlm.nih.gov/pubmed/21196490", "http://www.ncbi.nlm.nih.gov/pubmed/22974708", "http://www.ncbi.nlm.nih.gov/pubmed/22210878" ], "ideal_answer": [ "So far, mutations in Notch and other components of its signaling pathway have been implicated in an array of human diseases (T-cell leukemia and other cancers, Multiple Sclerosis, CADASIL, Alagille Syndrome, Spondylocostal Dysostosis), but more pathologies are likely to be associated with Notch in the future due to its network complexity." ], "exact_answer": [ [ "Alagille syndrome" ], [ "spondylocostal dysostosis" ], [ "CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)" ], [ "T-cell acute lymphoblastic leukemia" ] ], "type": "list", "id": "5173eb428ed59a060a000021", "snippets": [ { "offsetInBeginSection": 954, "offsetInEndSection": 1073, "text": "Comparative functional genomic analysis identified a signature of Notch activation in 30% of HCC samples from patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22974708", "endSection": "sections.0" }, { "offsetInBeginSection": 450, "offsetInEndSection": 705, "text": "Here, we performed whole transcriptome sequencing on a discovery cohort of 18 primary tissue MCL samples and 2 cell lines. We found recurrent mutations in NOTCH1, a finding that we confirmed in an extension cohort of 108 clinical samples and 8 cell lines.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22210878", "endSection": "sections.0" }, { "offsetInBeginSection": 466, "offsetInEndSection": 714, "text": "We found activating mutations in Notch in more than 30% of ATL patients. These activating mutations are phenotypically different from those previously reported in T-ALL leukemias and may represent polymorphisms for activated Notch in human cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20823234", "endSection": "sections.0" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1429, "text": "We detected Notch1 missense mutations in 8.3% of the tumors (only in the posterior fossa location and in case of 9q33-34 gain).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289631", "endSection": "sections.0" }, { "offsetInBeginSection": 114, "offsetInEndSection": 360, "text": "Importantly, mutations of the Notch protein and components of its signaling pathway have been implicated in an array of human diseases (T-cell leukemia and other cancers, Multiple Sclerosis, CADASIL, Alagille Syndrome, Spondylocostal Dysostosis).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584081", "endSection": "sections.0" }, { "offsetInBeginSection": 606, "offsetInEndSection": 786, "text": "Here, we demonstrate that endothelial-specific deletion of Jag1 leads to cardiovascular defects in both embryonic and adult mice that are reminiscent of those in Alagille syndrome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095891", "endSection": "sections.0" }, { "offsetInBeginSection": 270, "offsetInEndSection": 493, "text": "In this study, analysis of 21 Vietnamese ALGS individuals led to the identification of 19 different mutations (18 JAG1 and 1 NOTCH2), 17 of which are novel, including the third reported NOTCH2 mutation in Alagille Syndrome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488849", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196490", "endSection": "sections.0" }, { "offsetInBeginSection": 344, "offsetInEndSection": 839, "text": "Four genes causing a subset of autosomal recessive forms of this disease have been identified: DLL3 (SCDO1: MIM 277300), MESP2 (SCDO2: MIM 608681), LFNG (SCDO3: MIM609813) and HES7 (SCDO4). These genes are all essential components of the Notch signalling pathway, which has multiple roles in development and disease. Previously, only a single SCD-causative missense mutation was described in HES7. In this study, we have identified two new missense mutations in the HES7 gene in a single family,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20087400", "endSection": "sections.0" }, { "offsetInBeginSection": 647, "offsetInEndSection": 816, "text": "Here we have used autozygosity mapping to identify a mutation in a fourth Notch pathway gene, Hairy-and-Enhancer-of-Split-7 (HES7), in an autosomal recessive SCD family.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18775957", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 432, "text": "Alagille syndrome (AGS) is caused by mutations in the gene for the Notch signaling pathway ligand Jagged1 (JAG1), which are found in 94% of patients. To identify the cause of disease in patients without JAG1 mutations, we screened 11 JAG1 mutation-negative probands with AGS for alterations in the gene for the Notch2 receptor (NOTCH2). We found NOTCH2 mutations segregating in two families and identified five affected individuals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16773578", "endSection": "sections.0" }, { "offsetInBeginSection": 139, "offsetInEndSection": 381, "text": "Mutations in the JAG1 (Jagged 1) gene, coding a ligand in the evolutionarily conserved Notch signaling pathway, are responsible for AGS. Here we present sixteen different JAG1 gene mutations, among them twelve novel, not described previously.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15712272", "endSection": "sections.0" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1168, "text": "Altogether 226 different JAG1 mutations have been described in association with AGS, including our novel 36 mutations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12497640", "endSection": "sections.0" }, { "offsetInBeginSection": 163, "offsetInEndSection": 603, "text": "Previous studies have demonstrated that a wide spectrum of JAG1 mutations result in AGS. These include total gene deletions, protein truncating, splicing and missense mutations which are distributed across the coding region of the gene. Here we present results of JAG1 mutation screening by SSCP and FISH in 105 patients with AGS. For these studies, new primers were designed for 12 exons. Mutations were identified in 63/105 patients (60%)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11180599", "endSection": "sections.0" }, { "offsetInBeginSection": 445, "offsetInEndSection": 916, "text": "We have screened 54 AGS probands and family members to determine the frequency of mutations in JAG1. Three patients (6%) had deletions of the entire gene. Of the remaining 51 patients, 35 (69%) had mutations within JAG1, identified by SSCP analysis. Of the 35 identified intragenic mutations, all were unique, with the exceptions of a 5-bp deletion in exon 16, seen in two unrelated patients, and a C insertion at base 1618 in exon 9, also seen in two unrelated patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9585603", "endSection": "sections.0" }, { "offsetInBeginSection": 157, "offsetInEndSection": 534, "text": "Analyses of many patients with cytogenetic deletions or rearrangements have mapped the gene to chromosome 20p12, although deletions are found in a relatively small proportion of patients (< 7%). We have mapped the human Jagged1 gene (JAG1), encoding a ligand for the developmentally important Notch transmembrane receptor, to the Alagille syndrome critical region within 20p12.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9207788", "endSection": "sections.0" } ] }, { "body": "Can cognitive behavioral therapy improve fatigue in cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20890148", "http://www.ncbi.nlm.nih.gov/pubmed/21538678", "http://www.ncbi.nlm.nih.gov/pubmed/25233905", "http://www.ncbi.nlm.nih.gov/pubmed/25299140", "http://www.ncbi.nlm.nih.gov/pubmed/21372697", "http://www.ncbi.nlm.nih.gov/pubmed/20651011", "http://www.ncbi.nlm.nih.gov/pubmed/24971014", "http://www.ncbi.nlm.nih.gov/pubmed/17050873", "http://www.ncbi.nlm.nih.gov/pubmed/19450037", "http://www.ncbi.nlm.nih.gov/pubmed/24419112", "http://www.ncbi.nlm.nih.gov/pubmed/23707383", "http://www.ncbi.nlm.nih.gov/pubmed/19090531", "http://www.ncbi.nlm.nih.gov/pubmed/18246853", "http://www.ncbi.nlm.nih.gov/pubmed/24458595", "http://www.ncbi.nlm.nih.gov/pubmed/23557323", "http://www.ncbi.nlm.nih.gov/pubmed/25083010", "http://www.ncbi.nlm.nih.gov/pubmed/24650832", "http://www.ncbi.nlm.nih.gov/pubmed/18310181", "http://www.ncbi.nlm.nih.gov/pubmed/25150812", "http://www.ncbi.nlm.nih.gov/pubmed/22926087", "http://www.ncbi.nlm.nih.gov/pubmed/19900778", "http://www.ncbi.nlm.nih.gov/pubmed/20656618", "http://www.ncbi.nlm.nih.gov/pubmed/20930100" ], "ideal_answer": [ "Yes, it has been documented that cognitive behavioral therapy reduces fatigue symptom severity in cancer patients. In addition, cognitive behavioral therapy has been also shown to improve mood and overall quality of life, and it can be successfully delivered through a variety of treatment modalities in patients with cancer." ], "exact_answer": "yes", "type": "yesno", "id": "54d762653706e89528000014", "snippets": [ { "offsetInBeginSection": 536, "offsetInEndSection": 697, "text": "Physical activity, educational interventions, and cognitive-behavioral therapy have the most supportive data and can be recommended to patients with confidence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25299140", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1327, "text": "For women undergoing radiotherapy (3 RCTs), hypnosis combined with cognitive-behavioral therapy improved distress and fatigue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25233905", "endSection": "abstract" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1452, "text": "Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25150812", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1327, "text": "However, relative to VCBT-I, PCBT-I was associated with significantly greater improvements of insomnia severity, early morning awakenings, depression, fatigue, and dysfunctional beliefs about sleep. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25083010", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1458, "text": "CBT-I may also improve mood, fatigue, and overall quality of life, and can be successfully delivered through a variety of treatment modalities, making it possible to reach a broader range of patients who may not have access to more traditional programs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971014", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1378, "text": "No group differences in improvement were noted relative to QOL, fatigue, or mood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650832", "endSection": "abstract" }, { "offsetInBeginSection": 1715, "offsetInEndSection": 1806, "text": "In case of persistent fatigue, personalized cognitive behavioral therapy can be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458595", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1567, "text": "ONCLUSION: The results support CBTH as an evidence-based intervention to control fatigue in patients undergoing radiotherapy for breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24419112", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 331, "text": "Severe fatigue after cancer treatment can be treated effectively with cognitive behavioral therapy (CBT), but it is unclear whether CBT has an effect on cognitive functioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707383", "endSection": "abstract" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1681, "text": "CONCLUSION: CBT for post-cancer fatigue has already been shown to be an effective therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707383", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 549, "text": "Frequently reported side effects include cancer-related fatigue, peripheral neuropathy, and psychological distress. Exercise and cognitive behavioral therapy interventions have counteracted such adverse effects in other cancer populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23557323", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1142, "text": "There is evidence from methodologically rigorous controlled trials that exercise, psycho-educational interventions, and cognitive-behavioral therapy for insomnia are effective in the treatment of CRF, and a wide range of pharmacologic and nonpharmacologic interventions has shown initial promise in single-arm pilot studies with small, heterogeneous samples. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20656618", "endSection": "abstract" }, { "offsetInBeginSection": 2060, "offsetInEndSection": 2535, "text": "CONCLUSIONS: Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20651011", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1262, "text": "RESULTS: Imagery/hypnosis and CBT/CST interventions have produced improvement in all the three cancer-related symptoms individually: pain, fatigue, and sleep disturbance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19900778", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1139, "text": "RESULTS: Multilevel modeling indicated that for weekly FACIT fatigue data, there was a significant effect of the CBTH intervention on the rate of change in fatigue (p < .05), such that on average, CBTH participants' fatigue did not increase over the course of treatment, whereas control group participants' fatigue increased linearly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450037", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1347, "text": "ONCLUSION: The results suggest that CBTH is an effective means for controlling and potentially preventing fatigue in breast cancer radiotherapy patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450037", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 596, "text": "Results were consistent with the view that CBTH was effective in managing fatigue and skin discomfort, and increasing relaxation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18246853", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1314, "text": "RESULTS: Participants in the Internet group showed significant improvements at post-assessment compared with those in the control group in overall insomnia severity (F(1,26) = 22.8; p<0.001), sleep efficiency (F(1,24) = 11.45; P = 0.002), sleep onset latency (F(1,24) = 5.18; P = 0.03), soundness of sleep (F(1,24) = 9.34; P = 0.005), restored feeling upon awakening (F(1,24) = 11.95; P = 0.002), and general fatigue (F(1,26) = 13.88; P = 0.001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21538678", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 339, "text": "Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21372697", "endSection": "abstract" }, { "offsetInBeginSection": 2243, "offsetInEndSection": 2535, "text": "Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20651011", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 327, "text": "Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21372697", "endSection": "abstract" }, { "offsetInBeginSection": 2151, "offsetInEndSection": 2443, "text": "Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20651011", "endSection": "abstract" }, { "offsetInBeginSection": 1892, "offsetInEndSection": 2038, "text": "The positive effects of cognitive behavioral therapy in adolescents with chronic fatigue syndrome are sustained after cognitive behavioral therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18310181", "endSection": "abstract" } ] }, { "body": "Is protein Fbw7 a SCF type of E3 ubiquitin ligase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22665065", "http://www.ncbi.nlm.nih.gov/pubmed/21349854", "http://www.ncbi.nlm.nih.gov/pubmed/23507969", "http://www.ncbi.nlm.nih.gov/pubmed/20826802", "http://www.ncbi.nlm.nih.gov/pubmed/20935640", "http://www.ncbi.nlm.nih.gov/pubmed/21282377", "http://www.ncbi.nlm.nih.gov/pubmed/22124735", "http://www.ncbi.nlm.nih.gov/pubmed/14672936", "http://www.ncbi.nlm.nih.gov/pubmed/18094723", "http://www.ncbi.nlm.nih.gov/pubmed/19679664", "http://www.ncbi.nlm.nih.gov/pubmed/22608923", "http://www.ncbi.nlm.nih.gov/pubmed/23820376", "http://www.ncbi.nlm.nih.gov/pubmed/23776410", "http://www.ncbi.nlm.nih.gov/pubmed/21827743" ], "ideal_answer": [ "Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members.The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun.", "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044843", "http://www.uniprot.org/uniprot/SKP1_ASPFN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044767" ], "type": "yesno", "id": "550ae16bc2af5d5b70000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18094723", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 700, "text": "However, very few E3 ubiquitin ligases are known to target G-CSFR for ubiquitin-proteasome pathway. Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23820376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23776410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF(FBW7) (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23507969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The tumor suppressor Fbxw7 (also known as Sel-10, hCdc4, hAgo, or Fbw7) is an F-box protein that functions as the substrate-recognition subunit of an SCF ubiquitin ligase complex and targets a group of oncoproteins for degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Fbw7 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22608923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Fbw7 is a member of F-box family proteins, which constitute one subunit of Skp1, Cul1, and F-box protein (SCF) ubiquitin ligase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22124735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 485, "text": "Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21349854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "The Fbxw7 (F-box/WD repeat-containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues and targets multiple transcriptional activators and protooncogenes for ubiquitin-mediated degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 475, "text": "We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20935640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The SCF(Fbw7) ubiquitin ligase complex plays important roles in cell growth, survival, and differentiation via the ubiquitin-proteasome-mediated regulation of protein stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19679664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and mammalian target of rapamycin (mTOR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20826802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Mammalian Fbw7 (also known as Sel-10, hCdc4, or hAgo) is the F-box protein component of an SCF (Skp1-Cul1-F-box protein-Rbx1)-type ubiquitin ligase, and the mouse Fbw7 is expressed prominently in the endothelial cell lineage of embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14672936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21827743", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 476, "text": "We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20935640", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 699, "text": "Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23820376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23776410", "endSection": "abstract" } ] }, { "body": "Is there increased incidence of incontinence in athletes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19415493", "http://www.ncbi.nlm.nih.gov/pubmed/15385857", "http://www.ncbi.nlm.nih.gov/pubmed/16953954", "http://www.ncbi.nlm.nih.gov/pubmed/17390923", "http://www.ncbi.nlm.nih.gov/pubmed/15233598", "http://www.ncbi.nlm.nih.gov/pubmed/20390664", "http://www.ncbi.nlm.nih.gov/pubmed/20890872", "http://www.ncbi.nlm.nih.gov/pubmed/21571270", "http://www.ncbi.nlm.nih.gov/pubmed/23687004", "http://www.ncbi.nlm.nih.gov/pubmed/11689727", "http://www.ncbi.nlm.nih.gov/pubmed/23122895", "http://www.ncbi.nlm.nih.gov/pubmed/8684695", "http://www.ncbi.nlm.nih.gov/pubmed/23361854", "http://www.ncbi.nlm.nih.gov/pubmed/10932809", "http://www.ncbi.nlm.nih.gov/pubmed/18506324", "http://www.ncbi.nlm.nih.gov/pubmed/8041527", "http://www.ncbi.nlm.nih.gov/pubmed/11999199", "http://www.ncbi.nlm.nih.gov/pubmed/21501085" ], "ideal_answer": [ "There is a very high prevalence of urinary incontinence in women athletes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014550", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014549" ], "type": "yesno", "id": "5361677c7d100faa09000008", "snippets": [ { "offsetInBeginSection": 270, "offsetInEndSection": 482, "text": "Urinary incontinence affects women of all ages, including top female athletes, but is often under-reported. The highest prevalence of urinary incontinence is reported in those participating in high impact sports.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23687004", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 196, "text": "The prevalence of female stress urinary incontinence is high, and young adults are also affected, including athletes, especially those involved in \"high-impact\" sports", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23361854", "endSection": "abstract" }, { "offsetInBeginSection": 1841, "offsetInEndSection": 2074, "text": "Analysis of these data suggests that perineal pressure is decreased in female athletes compared with nonathlete women. A lower perineal pressure correlates with increased symptoms of urinary incontinence and pelvic floor dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122895", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1033, "text": "Urinary incontinence is a prevalent condition among athletes that is not openly discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21571270", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1564, "text": "High-level sport appears to be a significant independent risk factor for AI in healthy young women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501085", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 671, "text": "The prevalence of LUTS was 54.7%, and 30% for urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20890872", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1583, "text": "LUTS and incontinence are prevalent in female athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20890872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "A relationship between sport or fitness activities and urinary incontinence (UI) previously has been described in women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20390664", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 294, "text": "studies have also shown a high prevalence of SUI in young, physically fit female athletes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19415493", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 830, "text": "There was urinary incontinence in female long-distance runners and a correlation with eating disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18506324", "endSection": "abstract" }, { "offsetInBeginSection": 31, "offsetInEndSection": 136, "text": "young female athletes participating in high-impact sports may be at higher risk for urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17390923", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 631, "text": "Results indicated that more than 25% of those completing surveys experienced incontinence and that more than 90% had never told anyone about their problem and had no knowledge of preventive measures; 16% reported incontinence negatively impacted their quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17390923", "endSection": "abstract" }, { "offsetInBeginSection": 1303, "offsetInEndSection": 1377, "text": "There is a very high prevalence of urinary incontinence in women athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16953954", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 832, "text": "Women athletes should be counseled about the increased risk of urinary incontinence with ultra high-impact sports and eating disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15385857", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 1036, "text": "Stress urinary incontinence is a barrier to women's participation in sport and fitness activities and, therefore, it may be a threat to women's health, self-esteem and well-being. The prevalence during sports among young, nulliparous elite athletes varies between 0% (golf) and 80% (trampolinists). The highest prevalence is found in sports involving high impact activities such as gymnastics, track and field, and some ball games", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15233598", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1330, "text": "Urinary leakage is common among elite athletes and dancers, particularly during training, but also during daily life activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11999199", "endSection": "abstract" }, { "offsetInBeginSection": 1850, "offsetInEndSection": 2064, "text": "There is a high prevalence of stress and urge incontinence in female elite athletes. The frequency of SUI and urge incontinence was significantly higher in eating disordered athletes compared with healthy athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11689727", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1419, "text": "High impact sports activities may produce urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10932809", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 906, "text": "Urinary incontinence during physical stresses is common in young nulliparous wome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8684695", "endSection": "abstract" }, { "offsetInBeginSection": 1307, "offsetInEndSection": 1395, "text": "Incontinence during physical stresses is common in young, highly fit, nulliparous women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8041527", "endSection": "abstract" } ] }, { "body": "What is the inheritance pattern of Apert syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19089249", "http://www.ncbi.nlm.nih.gov/pubmed/11057397", "http://www.ncbi.nlm.nih.gov/pubmed/16354263", "http://www.ncbi.nlm.nih.gov/pubmed/3359672", "http://www.ncbi.nlm.nih.gov/pubmed/16440883", "http://www.ncbi.nlm.nih.gov/pubmed/2061407", "http://www.ncbi.nlm.nih.gov/pubmed/8830082" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0121961", "o": "D000168" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0001193", "o": "http://linkedlifedata.com/resource/umls/label/A11936347" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0001193", "o": "http://linkedlifedata.com/resource/umls/label/A17816121" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11936347", "o": "APERT SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11965023", "o": "ACROCEPHALOSYNDACTYLY, TYPE I" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12036491", "o": "ACS I" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0001193", "o": "http://linkedlifedata.com/resource/umls/label/A11965023" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469293", "o": "Syndactylic Oxycephaly" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17816121", "o": "Acrocephalosyndactyly [Apert]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": 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"http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17816121", "o": "Q87.0" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8339679", "o": "755.55" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11936347", "o": "101200" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11965023", "o": "101200" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11993847", "o": "101200" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12036491", "o": "101200" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17816121", "o": "ICD-10-CM" } ], "ideal_answer": [ "The Apert syndrome is a disorder of autosomal dominant inheritance." ], "exact_answer": [ "Autosomal dominant" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.disease-ontology.org/api/metadata/DOID:12960", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000168", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918" ], "type": "factoid", "id": "52c7275103868f1b0600001c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 310, "text": "The Apert syndrome is a rare disorder of autosomal dominant inheritance caused by mutations in the FGFR2 gene at locus 10q26; patients with this syndrome present severe syndactyly, exophthalmia, ocular hypertelorism and hypoplastic midface with Class III malocclusion, besides systemic alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19089249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "The Apert syndrome is characterized by craniosynostosis and syndactyly of hands and feet. Although most cases are sporadic, an autosomal dominant mode of inheritance is well documented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16440883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Apert syndrome, or acrocephalosyndactyly, is characterized by craniosynostosis and early epiphyseal closure resulting in various deformities of the skull, hands, and feet. Typically a sporadic condition, autosomal dominant inheritance with complete penetrance has been known to occur. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16354263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "We report two observations of antenatal diagnosis of Apert syndrome. This uncommon genetic disorder suggest an autosomal dominant inheritance, but almost all cases described are sporadic; the responsible gene is yet not located.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8830082", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 572, "text": "The familial cases, the equal number of affected males and females, and the increased paternal age in sporadic cases strongly suggest autosomal dominant inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2061407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "This report presents the first example of male transmission of Apert acrocephalosyndactyly syndrome. Female transmission has been reported in the five previous well-documented cases of dominant inheritance of the syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3359672", "endSection": "abstract" } ] }, { "body": "Which is the most widely used model for the study of multiple sclerosis (MS)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15898103", "http://www.ncbi.nlm.nih.gov/pubmed/21029240", "http://www.ncbi.nlm.nih.gov/pubmed/11391780", "http://www.ncbi.nlm.nih.gov/pubmed/23161666", "http://www.ncbi.nlm.nih.gov/pubmed/15039233", "http://www.ncbi.nlm.nih.gov/pubmed/20829083", "http://www.ncbi.nlm.nih.gov/pubmed/7739505", "http://www.ncbi.nlm.nih.gov/pubmed/19361871", "http://www.ncbi.nlm.nih.gov/pubmed/16106061", "http://www.ncbi.nlm.nih.gov/pubmed/11829341", "http://www.ncbi.nlm.nih.gov/pubmed/15929040", "http://www.ncbi.nlm.nih.gov/pubmed/1793022", "http://www.ncbi.nlm.nih.gov/pubmed/16137612", "http://www.ncbi.nlm.nih.gov/pubmed/21255614", "http://www.ncbi.nlm.nih.gov/pubmed/19894121", "http://www.ncbi.nlm.nih.gov/pubmed/18673215", "http://www.ncbi.nlm.nih.gov/pubmed/15949496", "http://www.ncbi.nlm.nih.gov/pubmed/22530047", "http://www.ncbi.nlm.nih.gov/pubmed/15492125", "http://www.ncbi.nlm.nih.gov/pubmed/15288396", "http://www.ncbi.nlm.nih.gov/pubmed/17463082", "http://www.ncbi.nlm.nih.gov/pubmed/18773082", "http://www.ncbi.nlm.nih.gov/pubmed/18950873", "http://www.ncbi.nlm.nih.gov/pubmed/16440059", "http://www.ncbi.nlm.nih.gov/pubmed/20623621", "http://www.ncbi.nlm.nih.gov/pubmed/17343922", "http://www.ncbi.nlm.nih.gov/pubmed/17766043", "http://www.ncbi.nlm.nih.gov/pubmed/16126908", "http://www.ncbi.nlm.nih.gov/pubmed/15265674", "http://www.ncbi.nlm.nih.gov/pubmed/22272832" ], "ideal_answer": [ "Experimental autoimmune encephalomyelitis (EAE) is a classical, conventional and widely recognized animal model for studying multiple sclerosis (MS). EAE is the best available model for the inflammatory processes that occur in MS, and for the disease process. A less commonly used model is that of Theiler's murine encephalomyelitis virus (TMEV)." ], "exact_answer": [ "Experimental autoimmune encephalomyelitis (EAE)" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2376", "http://www.disease-ontology.org/api/metadata/DOID:2377", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103" ], "type": "factoid", "id": "5139b31dbee46bd34c000004", "snippets": [ { "offsetInBeginSection": 241, "offsetInEndSection": 323, "text": "experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161666", "endSection": "sections.0" }, { "offsetInBeginSection": 282, "offsetInEndSection": 427, "text": "Many aspects of MS can be mimicked in the animal model of myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (MOG-EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21255614", "endSection": "sections.0" }, { "offsetInBeginSection": 531, "offsetInEndSection": 608, "text": "the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21029240", "endSection": "sections.0" }, { "offsetInBeginSection": 343, "offsetInEndSection": 548, "text": "The aim of our study was to characterize the sensory abnormalities and in particular the clinical signs linked to persistent pain in two models of Experimental Autoimmune Encephalomyelitis (EAE) in the rat", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20829083", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Experimental autoimmune encephalomyelitis (EAE) is an animal model for studying multiple sclerosis (MS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20623621", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Theiler's murine encephalomyelitis virus (TMEV) infection of mice is an experimental model for multiple sclerosis (MS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19894121", "endSection": "sections.0" }, { "offsetInBeginSection": 508, "offsetInEndSection": 599, "text": "experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19361871", "endSection": "sections.0" }, { "offsetInBeginSection": 448, "offsetInEndSection": 593, "text": "In this study we investigated whether in an animal model for MS, namely in experimental autoimmune encephalomyelitis (EAE), similar changes occur", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18950873", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Experimental autoimmune encephalomyelitis (EAE), a widely recognized animal model of multiple sclerosis (MS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18673215", "endSection": "sections.0" }, { "offsetInBeginSection": 196, "offsetInEndSection": 271, "text": "we utilized the Theiler's murine encephalomyelitis virus (TMEV) model of MS", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17766043", "endSection": "sections.0" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1027, "text": "In a murine disease model, experimental autoimmune encephalomyelitis (EAE) mice lacking cyclophilin D (CyPD)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17463082", "endSection": "sections.0" }, { "offsetInBeginSection": 45, "offsetInEndSection": 125, "text": "experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17463082", "endSection": "title" }, { "offsetInBeginSection": 613, "offsetInEndSection": 660, "text": "Theiler's murine encephalomyelitis virus (TMEV)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17343922", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Inflammatory diseases of the CNS, such as MS and its animal model EAE", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16440059", "endSection": "sections.0" }, { "offsetInBeginSection": 152, "offsetInEndSection": 243, "text": "the strong impact of the classical MS model experimental autoimmune encephalomyelitis (EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16137612", "endSection": "sections.0" }, { "offsetInBeginSection": 43, "offsetInEndSection": 191, "text": "an animal model of multiple sclerosis (MS): disease modifying activity on acute and chronic relapsing experimental allergic encephalomyelitis (EAE).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1793022", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7739505", "endSection": "title" }, { "offsetInBeginSection": 178, "offsetInEndSection": 286, "text": "EAE is the best available model for the inflammatory processes that occur in MS, and for the disease process", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7739505", "endSection": "sections.0" }, { "offsetInBeginSection": 455, "offsetInEndSection": 561, "text": "The present study addressed this question using the model of experimental allergic encephalomyelitis (EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11391780", "endSection": "sections.0" }, { "offsetInBeginSection": 261, "offsetInEndSection": 345, "text": "The conventional animal model of MS, experimental autoimmune encephalomyelitis (EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15039233", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "To assess neurological impairments quantitatively in an animal model of multiple sclerosis (MS), we have used a targeted model of experimental autoimmune encephalomyelitis (EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265674", "endSection": "sections.0" }, { "offsetInBeginSection": 155, "offsetInEndSection": 362, "text": "Experimental autoimmune encephalomyelitis (EAE) is a well-studied disease in rodents that mimics many clinical and pathological features of MS, including central nervous system inflammation and demyelination", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15288396", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), its animal model, involve inflammatory attack on central nervous system (CNS) white matter", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15898103", "endSection": "sections.0" }, { "offsetInBeginSection": 370, "offsetInEndSection": 459, "text": "both MS patients and the MS animal model, experimental autoimmune encephalomyelitis (EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15929040", "endSection": "sections.0" }, { "offsetInBeginSection": 289, "offsetInEndSection": 359, "text": "In the MS animal model experimental autoimmune encephalomyelitis (EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15949496", "endSection": "sections.0" }, { "offsetInBeginSection": 20, "offsetInEndSection": 102, "text": "multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16106061", "endSection": "title" }, { "offsetInBeginSection": 143, "offsetInEndSection": 256, "text": "inflammatory demyelination in multiple sclerosis (MS) lesions and experimental autoimmune encephalomyelitis (EAE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126908", "endSection": "sections.0" } ] }, { "body": "What is the usual HER-2 status in breast cancer associated with Li-Fraumeni syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23580068", "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "http://www.ncbi.nlm.nih.gov/pubmed/22392042" ], "ideal_answer": [ "In up to two thirds of breast cancer patients associated with Li-Fraumeni syndrome, the HER-2 status was found to be positive." ], "exact_answer": [ "Positive" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1612", "http://www.disease-ontology.org/api/metadata/DOID:0060079", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943", "http://www.disease-ontology.org/api/metadata/DOID:0050671", "http://www.disease-ontology.org/api/metadata/DOID:3012", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018579", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016864" ], "type": "factoid", "id": "52f21b722059c6d71c00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2+ (63-83 %).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580068", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 403, "text": "Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392042", "endSection": "abstract" }, { "offsetInBeginSection": 1682, "offsetInEndSection": 1782, "text": "Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Early onset HER2-positive breast cancer is associated with germline TP53 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 130, "text": "Germline TP53 mutations predispose to early onset breast cancer in women and are associated with Li-Fraumeni syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 895, "text": "Patients who tested positive for germlineTP53 mutations (n = 30) were compared with controls (n = 79). Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared with 25% for the controls (P = .0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "endSection": "abstract" }, { "offsetInBeginSection": 1445, "offsetInEndSection": 1556, "text": "This study suggests an association between germline TP53 mutations and early onset HER2-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "The Li-Fraumeni Syndrome is caused by a germline TP53 mutation and is associated with a high risk of breast cancer at young ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 1035, "text": "Patients carrying a TP53 mutation showed a significantly higher likelihood of developing a breast cancer with Human Epidermal growth factor Receptor (HER2) amplification (83%) when compared to the cohort of young onset breast cancer cases (16%);", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1252, "text": "breast cancer developing on a background of an inherited TP53 mutation is highly likely to present with amplification of HER2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805372", "endSection": "abstract" } ] }, { "body": "What is the treatment of triiodothyronine toxicosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8154510", "http://www.ncbi.nlm.nih.gov/pubmed/7296908", "http://www.ncbi.nlm.nih.gov/pubmed/578375", "http://www.ncbi.nlm.nih.gov/pubmed/16042328", "http://www.ncbi.nlm.nih.gov/pubmed/16889493" ], "ideal_answer": [ "Treatment of T3 toxicosis is a complex medical problem because not well responsive to the various options. Usual treatment includes antithyroid drugs such as propyltiouracil, radioactive iodine or beta blockers like propanol; surgery may be also necessary in some cases." ], "exact_answer": [ [ "Propyltiouracil" ], [ "Radioiodine" ], [ "beta blockers" ], [ "thyroidectomy" ] ], "type": "list", "id": "518cb6ab310faafe08000009", "snippets": [ { "offsetInBeginSection": 1346, "offsetInEndSection": 1650, "text": "Three patients met the criteria for free T3 toxicosis and three had subclinical hyperthyroidism. All six patients had either multinodular glands or a single nodule on thyroid exam. Four patients were treated with radioactive iodine or surgery, resulting in reversal of the TSH suppression in three cases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8154510", "endSection": "sections.0" }, { "offsetInBeginSection": 69, "offsetInEndSection": 308, "text": "6 months treatment with propranolol (160 mg/day) in eight patients with T3 (triiodothyronine) toxicosis. Serum total T3 concentrations showed a significant (p less than 0.01) and sustained fall to approximately 80% of pre-treatment values.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7296908", "endSection": "sections.0" }, { "offsetInBeginSection": 490, "offsetInEndSection": 547, "text": "Both patients responded to therapy with propylthiouracil.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/578375", "endSection": "sections.0" } ] }, { "body": "Are there enhancer RNAs (eRNAs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24674738", "http://www.ncbi.nlm.nih.gov/pubmed/23877407", "http://www.ncbi.nlm.nih.gov/pubmed/25810254", "http://www.ncbi.nlm.nih.gov/pubmed/24525859", "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "http://www.ncbi.nlm.nih.gov/pubmed/24135681", "http://www.ncbi.nlm.nih.gov/pubmed/25404134", "http://www.ncbi.nlm.nih.gov/pubmed/25263592", "http://www.ncbi.nlm.nih.gov/pubmed/20393465", "http://www.ncbi.nlm.nih.gov/pubmed/24480293", "http://www.ncbi.nlm.nih.gov/pubmed/23728302" ], "ideal_answer": [ "Yes. Active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004742", "http://amigo.geneontology.org/amigo/term/GO:0035326" ], "type": "yesno", "id": "56a8adb0a17756b72f000003", "snippets": [ { "offsetInBeginSection": 34, "offsetInEndSection": 293, "text": "active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 708, "text": " eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Enhancer RNAs and regulated transcriptional programs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24674738", "endSection": "title" }, { "offsetInBeginSection": 388, "offsetInEndSection": 503, "text": "enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24674738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "The emerging roles of eRNAs in transcriptional regulatory networks", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24525859", "endSection": "title" }, { "offsetInBeginSection": 615, "offsetInEndSection": 871, "text": "we found certain enhancer RNAs (eRNAs) regulate chromatin accessibility of the transcriptional machinery at loci encoding master regulators of myogenesis (i.e., MyoD/MyoG), thus suggesting their significance and site-specific impact in cellular programming", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24525859", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Enhancer RNAs: the new molecules of transcription", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24480293", "endSection": "title" }, { "offsetInBeginSection": 168, "offsetInEndSection": 407, "text": " the discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24480293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "eRNAs reach the heart of transcription", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877407", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263592", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 483, "text": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728302", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 290, "text": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728302", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 248, "text": "A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24135681", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 433, "text": "Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810254", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 405, "text": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728302", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 877, "text": "Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20393465", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 626, "text": "A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20393465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 413, "text": " Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263592", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 405, "text": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": " Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "endSection": "abstract" } ] }, { "body": "Which are the known human transmembrane nucleoporins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1281815", "http://www.ncbi.nlm.nih.gov/pubmed/20624389", "http://www.ncbi.nlm.nih.gov/pubmed/21444689", "http://www.ncbi.nlm.nih.gov/pubmed/12093788", "http://www.ncbi.nlm.nih.gov/pubmed/7561689", "http://www.ncbi.nlm.nih.gov/pubmed/16779818", "http://www.ncbi.nlm.nih.gov/pubmed/16600873", "http://www.ncbi.nlm.nih.gov/pubmed/15611332", "http://www.ncbi.nlm.nih.gov/pubmed/16682526", "http://www.ncbi.nlm.nih.gov/pubmed/11684705", "http://www.ncbi.nlm.nih.gov/pubmed/19703420", "http://www.ncbi.nlm.nih.gov/pubmed/11453980", "http://www.ncbi.nlm.nih.gov/pubmed/20566687", "http://www.ncbi.nlm.nih.gov/pubmed/9140728", "http://www.ncbi.nlm.nih.gov/pubmed/21189294", "http://www.ncbi.nlm.nih.gov/pubmed/20498018", "http://www.ncbi.nlm.nih.gov/pubmed/16702234", "http://www.ncbi.nlm.nih.gov/pubmed/16702233", "http://www.ncbi.nlm.nih.gov/pubmed/15613247", "http://www.ncbi.nlm.nih.gov/pubmed/22960634", "http://www.ncbi.nlm.nih.gov/pubmed/7504063", "http://www.ncbi.nlm.nih.gov/pubmed/20550937", "http://www.ncbi.nlm.nih.gov/pubmed/21727197", "http://www.ncbi.nlm.nih.gov/pubmed/12653556" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1721698", "o": "http://linkedlifedata.com/resource/umls/label/A12993781" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12993781", "o": "nucleoporin NDC1 protein, human" } ], "ideal_answer": [ "Transmembrane nucleoporins (NUPs) are integral membrane components of the eukaryotic nuclear pore, playing an important role in the Nuclear Pore Complex (NPC) assembly. Even though the NPC is a conserved feature of all eukaryotes, different lineages possess some distinct transmembrane NUP subunits. Currently, four human transmembrane NUPs have been characterized, namely: NDC1 (also known as TMEM48 or NET3 or hNDC1), POM121 (also known as Nup121), GP210 (also known as Nuclear pore membrane glycoprotein 210 or Nuclear envelope pore membrane protein POM 210, POM210 or Nup210) and TMEM33 (or DB83)." ], "exact_answer": [ [ "NDC1", "TMEM48", "NET3", "hNDC1" ], [ "POM121", "Nup121" ], [ "GP210", "Nuclear pore membrane glycoprotein 210", "Nuclear envelope pore membrane protein POM 210", "POM210", "Nup210" ], [ "TMEM33", "DB83" ] ], "concepts": [ "http://www.uniprot.org/uniprot/P121A_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021381", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016021", "http://www.uniprot.org/uniprot/PO210_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.uniprot.org/uniprot/TMM33_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D028861", "http://www.uniprot.org/uniprot/NDC1_HUMAN" ], "type": "list", "id": "51bdb644047fa84d1d000001", "snippets": [ { "offsetInBeginSection": 150, "offsetInEndSection": 245, "text": "We investigated the interplay between import receptors and the transmembrane nucleoporin Pom121", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624389", "endSection": "sections.0" }, { "offsetInBeginSection": 424, "offsetInEndSection": 576, "text": "the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20550937", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "The transmembrane nucleoporin NDC1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19703420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "NDC1 is a transmembrane nucleoporin that is required for NPC assembly and nucleocytoplasmic transport.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19703420", "endSection": "sections.0" }, { "offsetInBeginSection": 298, "offsetInEndSection": 803, "text": "The only protein known to localize to and be important in the assembly of both of these yeast structures is the integral membrane protein, Ndc1p. However, no homologues of Ndc1p had been characterized in metazoa. Here, we identify and analyze NDC1 homologues that are conserved throughout evolution. We show that the overall topology of these homologues is conserved. Each contains six transmembrane segments in its N-terminal half and has a large soluble C-terminal half of approximately 300 amino acids.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16779818", "endSection": "sections.0" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1214, "text": "Although it is not known whether vertebrate NDC1 protein localizes to nuclear pores like its yeast counterpart, the human homologue contains three FG repeats in the C-terminus, a feature of many nuclear pore proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16779818", "endSection": "sections.0" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1501, "text": "we bring together data from another study to demonstrate that the human homologue of NDC1 is the known inner nuclear membrane protein, NET3.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16779818", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "The conserved transmembrane nucleoporin NDC1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16600873", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 413, "text": "we characterize vertebrate NDC1--a transmembrane nucleoporin conserved between yeast and metazoans", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16600873", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "gp210 is a major constituent of the nuclear pore complex (NPC) with possible structural and regulatory roles. It interacts with components of the NPC via its C-terminal domain (CTD), which follows a transmembrane domain and a massive ( approximately 200 kDa) N-terminal region that resides in the lumen of the perinuclear space.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12653556", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The membrane-spanning glycoprotein gp210 is a major component of the nuclear pore complex. This nucleoporin contains a large cisternal N-terminal domain, a short C-terminal cytoplasmic tail, and a single transmembrane segment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11453980", "endSection": "sections.0" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1033, "text": "We propose that gp210 is organized into the pore membrane as a large array of gp210 dimers that may constitute a luminal submembranous protein skeleton.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11453980", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Patients with primary biliary cirrhosis (PBC) frequently produce autoantibodies against gp210, an integral glycoprotein of the nuclear pores. this protein consists of three main domains: a large glycosylated lumenal domain, a single hydrophobic transmembrane segment and a short cytoplasmic tail.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9140728", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Patients with primary biliary cirrhosis frequently develop autoantibodies directed to gp210, a major glycoprotein of the nuclear pore complex. This protein contains a large glycosylated cisternal domain, a single transmembrane segment, and a short cytoplasmic tail.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7561689", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7504063", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "Patients with primary biliary cirrhosis (PBC) frequently have autoantibodies against a 210-kD integral glycoprotein of the nuclear envelope pore membrane. This protein, termed gp210, has a 1,783-amino acid amino-terminal domain located in the perinuclear space, a 20-amino acid transmembrane segment, and a 58-amino acid cytoplasmic carboxy-terminal tail.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7504063", "endSection": "sections.0" }, { "offsetInBeginSection": 150, "offsetInEndSection": 246, "text": "We investigated the interplay between import receptors and the transmembrane nucleoporin Pom121.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624389", "endSection": "sections.0" }, { "offsetInBeginSection": 412, "offsetInEndSection": 576, "text": "Conversely, the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20550937", "endSection": "sections.0" }, { "offsetInBeginSection": 309, "offsetInEndSection": 414, "text": "Here, we characterize vertebrate NDC1--a transmembrane nucleoporin conserved between yeast and metazoans.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16600873", "endSection": "sections.0" }, { "offsetInBeginSection": 329, "offsetInEndSection": 441, "text": "Here, we report the solution structure of the human gp210 CTD as determined by various spectroscopic techniques.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12653556", "endSection": "sections.0" }, { "offsetInBeginSection": 486, "offsetInEndSection": 577, "text": "Using human gp210 isolated from HeLa cells we found the lumenal domain as the major target.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9140728", "endSection": "sections.0" }, { "offsetInBeginSection": 155, "offsetInEndSection": 355, "text": "This protein, termed gp210, has a 1,783-amino acid amino-terminal domain located in the perinuclear space, a 20-amino acid transmembrane segment, and a 58-amino acid cytoplasmic carboxy-terminal tail.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7504063", "endSection": "sections.0" }, { "offsetInBeginSection": 1652, "offsetInEndSection": 1864, "text": " In vertebrate cells, GLYCOPROTEIN OF 210 kD (gp210), PORE MEMBRANE PROTEIN OF 121 kD (Pom121), and NUCLEAR DIVISION CYCLE1 (NDC1) have been identified as integral pore membrane proteins (Cronshaw et al., 2002). ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21189294", "endSection": "sections.0" } ] }, { "body": "Which E3 ubiquitin ligase mediates the ubiquitination and degradation of the interferon receptor type 1 (IFNAR1)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19948722", "http://www.ncbi.nlm.nih.gov/pubmed/16551269", "http://www.ncbi.nlm.nih.gov/pubmed/17873516", "http://www.ncbi.nlm.nih.gov/pubmed/21173164", "http://www.ncbi.nlm.nih.gov/pubmed/14532120", "http://www.ncbi.nlm.nih.gov/pubmed/15337770", "http://www.ncbi.nlm.nih.gov/pubmed/18056411" ], "ideal_answer": [ "Ubiquitination and degradation of the IFNAR1 (interferon alpha receptor 1) subunit of the type I interferon (IFN) receptor is mediated by the SCFbeta-Trcp (Skp1-Cullin1-F-box protein beta transducin repeat-containing protein) E3 ubiquitin ligase in a phosphorylation-dependent manner.", "Ubiquitination, endocytosis, and lysosomal degradation of the IFNAR1 (interferon alpha receptor 1) subunit of the type I interferon (IFN) receptor is mediated by the SCFbeta-Trcp (Skp1-Cullin1-F-box protein beta transducin repeat-containing protein) E3 ubiquitin ligase in a phosphorylation-dependent manner. " ], "exact_answer": [ "\u03b2Trcp", "beta-Trcp", "SCFbeta-Trcp", "SCFbeta-Trcp (Skp1-Cullin1-F-box protein beta transducin repeat-containing protein)", "Skp1-Cullin1-HOS-Roc1 (SCF(HOS))" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044767" ], "type": "factoid", "id": "55192892622b194345000012", "snippets": [ { "offsetInBeginSection": 409, "offsetInEndSection": 571, "text": "IFNAR1 ubiquitination is facilitated by the \u03b2Trcp E3 ubiquitin ligase that is recruited to IFNAR1 upon its degron phosphorylation, which is induced by the ligand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21173164", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 730, "text": "Both ligand-dependent and -independent pathways converge on phosphorylation of Ser(535) within the IFNAR1 degron leading to recruitment of beta-Trcp E3 ubiquitin ligase and concomitant ubiquitination and degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948722", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 696, "text": "The SCF(betaTrcp) (Skp1-Cullin1-F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056411", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 480, "text": " Levels of IFNAR1 (regulated via degradation mediated by the betaTrcp E3 ubiquitin ligase) and IFNalpha signaling were reduced in 1205Lu melanoma cell line that harbors activated BRAF and exhibits high levels of betaTrcp ubiquitin ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17873516", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 641, "text": "IFNalpha promotes the phosphorylation of IFNAR1 on Ser535, followed by recruitment of the E3 ubiquitin ligase, beta-TrCP2 (beta-transducin repeats-containing protein 2), ubiquitination of IFNAR1 and proteolysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16551269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Ubiquitination, endocytosis, and lysosomal degradation of the IFNAR1 (interferon alpha receptor 1) subunit of the type I interferon (IFN) receptor is mediated by the SCFbeta-Trcp (Skp1-Cullin1-F-box protein beta transducin repeat-containing protein) E3 ubiquitin ligase in a phosphorylation-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15337770", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 570, "text": "Here we show that IFNAR1 interacts with the Homolog of Slimb (HOS) F-box protein in a phosphorylation-dependent manner, and that this interaction is promoted by interferon alpha (IFNalpha). IFNAR1 is ubiquitinated by the Skp1-Cullin1-HOS-Roc1 (SCF(HOS)) ubiquitin ligase in vitro. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14532120", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 693, "text": "The SCF(betaTrcp) (Skp1-Cullin1-F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056411", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 568, "text": "IFNAR1 ubiquitination is facilitated by the \u03b2Trcp E3 ubiquitin ligase that is recruited to IFNAR1 upon its degron phosphorylation, which is induced by the ligand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21173164", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 638, "text": "IFNalpha promotes the phosphorylation of IFNAR1 on Ser535, followed by recruitment of the E3 ubiquitin ligase, beta-TrCP2 (beta-transducin repeats-containing protein 2), ubiquitination of IFNAR1 and proteolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16551269", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 728, "text": "Both ligand-dependent and -independent pathways converge on phosphorylation of Ser(535) within the IFNAR1 degron leading to recruitment of beta-Trcp E3 ubiquitin ligase and concomitant ubiquitination and degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Ubiquitination, endocytosis, and lysosomal degradation of the IFNAR1 (interferon alpha receptor 1) subunit of the type I interferon (IFN) receptor is mediated by the SCFbeta-Trcp (Skp1-Cullin1-F-box protein beta transducin repeat-containing protein) E3 ubiquitin ligase in a phosphorylation-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15337770", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 695, "text": "The SCF(betaTrcp) (Skp1-Cullin1-F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056411", "endSection": "abstract" } ] }, { "body": "Are conserved noncoding elements associated with the evolution of animal body plans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19492354" ], "ideal_answer": [ "Yes. Cis-regulatory inputs identified by CNEs arose during the \"re-wiring\" of regulatory interactions that occurred during early animal evolution. Consequently, different animal groups, with different core GRNs, contain alternative sets of CNEs. Due to the subsequent stability of animal body plans, these core regulatory sequences have been evolving in parallel under strong purifying selection in different animal groups." ], "exact_answer": "yes", "type": "yesno", "id": "56b8a222156496395c000001", "snippets": [ { "offsetInBeginSection": 458, "offsetInEndSection": 1086, "text": "Here, we discuss the evidence that CNEs are part of the core gene regulatory networks (GRNs) that specify alternative animal body plans. The major animal groups arose>550 million years ago. We propose that the cis-regulatory inputs identified by CNEs arose during the \"re-wiring\" of regulatory interactions that occurred during early animal evolution. Consequently, different animal groups, with different core GRNs, contain alternative sets of CNEs. Due to the subsequent stability of animal body plans, these core regulatory sequences have been evolving in parallel under strong purifying selection in different animal groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Conserved noncoding elements and the evolution of animal body plans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Conserved noncoding elements and the evolution of animal body plans", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "endSection": "title" } ] }, { "body": "Which genes were found to be methylated in bladder cancer cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15041703", "http://www.ncbi.nlm.nih.gov/pubmed/20628239", "http://www.ncbi.nlm.nih.gov/pubmed/9515812", "http://www.ncbi.nlm.nih.gov/pubmed/16207479", "http://www.ncbi.nlm.nih.gov/pubmed/24324362", "http://www.ncbi.nlm.nih.gov/pubmed/21680534" ], "ideal_answer": [ "In bladder cancer, hepaCAM (hepatocyte cell adhesion molecule), RAR\u03b2(2), APC, TPEF (transmembrane protein containing epidermal growth factor and follistatin domain), RASSF1A, p14(ARF) and p16 genes were found to be methylated. These methylation events were demostrated to associate with downregulation of gene expression." ], "exact_answer": [ [ "hepaCAM (hepatocyte cell adhesion molecule)" ], [ "RAR\u03b2(2)" ], [ "APC" ], [ "TPEF (transmembrane protein containing epidermal growth factor and follistatin domain)" ], [ "RASSF1A" ], [ "p14(ARF)" ], [ "p16" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001749", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032259", "http://www.disease-ontology.org/api/metadata/DOID:4007", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016458", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://www.disease-ontology.org/api/metadata/DOID:7371", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032776", "http://www.disease-ontology.org/api/metadata/DOID:4006", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006306", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052138", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016147", "http://www.disease-ontology.org/api/metadata/DOID:11054" ], "type": "list", "id": "534ab91eaeec6fbd07000012", "snippets": [ { "offsetInBeginSection": 1223, "offsetInEndSection": 1443, "text": "CpG island in promoter of hepaCAM gene was hyper-methylated both in bladder carcinoma tissues and cell lines (T24 and BIU-87). Otherwise, aberrant methylation of its promoter was associated with its decreased expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324362", "endSection": "abstract" }, { "offsetInBeginSection": 1750, "offsetInEndSection": 1887, "text": "Abnormal hypermethylation in CpG island of hepaCAM promoter is involved in absence of hepaCAM gene expression when bladder cancer occurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324362", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 673, "text": "Methylated RAR\u03b2(2) and APC were significantly higher in bladder cancer patients (62.8%, 59.5%) than benign (16.4%, 5%) but not detected in healthy volunteers (0%) at (P < 0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680534", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 945, "text": "Among the 128 patients with bilharzial bladder cancer, 94 (73.4%) showed methylated RAR\u03b2(2) and 86 (67.2%) showed methylated APC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680534", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1573, "text": "Thus, methylated RAR\u03b2(2) and APC genes might be valuable urinary molecular markers for early detection of bilharzial and nonbilharzial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21680534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Exon 2 methylation inhibits hepaCAM expression in transitional cell carcinoma of the bladder", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20628239", "endSection": "title" }, { "offsetInBeginSection": 703, "offsetInEndSection": 831, "text": "the expression of hepaCAM was absent in T24 and BIU-87 cells, and we found that exon 2 of hepaCAM was methylated in the 2 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20628239", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 951, "text": "hepaCAM mRNA was re-expressed and the methylation status of hepaCAM exon 2 was reversed after treatment with 5-Aza-CdR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20628239", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1179, "text": "The methylation rate of hepaCAM exon 2 was significantly higher in bladder cancer tissues than in adjacent tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20628239", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 294, "text": "Recently, methylation of the TPEF (transmembrane protein containing epidermal growth factor and follistatin domain) gene was reported in human colon, gastric, and bladder cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16207479", "endSection": "abstract" }, { "offsetInBeginSection": 1499, "offsetInEndSection": 1645, "text": "Hypermethylation of at least one of three suppressor genes (APC, RASSF1A, and p14(ARF)) was found in all 45 tumor DNAs (100% diagnostic coverage).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15041703", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 813, "text": "Methylation of the CpG island in the promoter of the p16 gene in human bladder cancer cells did not stop the formation of a transcript initiated 20 kb upstream by the p19 promoter but did prevent the expression of a p16 transcript.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9515812", "endSection": "abstract" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1321, "text": "We also present the first functional evidence that methylation of only a small number of CpG sites can significantly down-regulate p16 promoter activity, thus providing support for the model of progressive inactivation of this tumor suppressor gene by DNA methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9515812", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1610, "text": "Hypermethylation of hepaCAM gene was reversed and expression of its mRNA and protein were re-activated in two cell lines by DNA methyltransferases inhibitor 5-aza-CdR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324362", "endSection": "abstract" } ] }, { "body": "Are DNA methylation maps applicable to the diagnosis of non-small-cell lung carcinomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "http://www.ncbi.nlm.nih.gov/pubmed/23524404" ], "ideal_answer": [ "Yes.", "yes" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002289", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003933", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008168", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.disease-ontology.org/api/metadata/DOID:3908", "http://amigo.geneontology.org/amigo/term/GO:0044030", "http://amigo.geneontology.org/amigo/term/GO:0006306", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055752", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://www.disease-ontology.org/api/metadata/DOID:5409", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018288" ], "type": "yesno", "id": "56ae69fb0a360a5e4500000d", "snippets": [ { "offsetInBeginSection": 438, "offsetInEndSection": 692, "text": "Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1501, "text": "Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identified 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1712, "text": "Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Genome-wide DNA methylation profiling of non-small cell lung carcinomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Genomewide DNA methylation analysis identifies novel methylated genes in non-small-cell lung carcinomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23524404", "endSection": "title" }, { "offsetInBeginSection": 525, "offsetInEndSection": 1006, "text": "To identify candidate markers for use in NSCLC diagnosis, we used genomewide DNA methylation maps that we had previously generated by MethylCap and next-generation sequencing and listed the most significant differentially methylated regions (DMRs). The 25 DMRs with highest significance in their methylation scores were selected. The methylation status of these DMRs was investigated in 61 tumors and matching control lung tissues by methylation-specific polymerase chain reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23524404", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1407, "text": "We found 12 novel DMRs that showed significant differences between tumor and control lung tissues. We also identified three novel DMRs for each of the two most common NSCLC subtypes, adenocarcinomas and squamous cell carcinomas. We propose a panel of five DMRs, composed of novel and known markers that exhibit high specificity and sensitivity to distinguish tumors from control lung tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23524404", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 931, "text": "Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 681, "text": "It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 810, "text": "Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 681, "text": "Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726460", "endSection": "abstract" } ] }, { "body": "Which domain of TIA-1 is necessary for stress granule assembly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18775331", "http://www.ncbi.nlm.nih.gov/pubmed/24981173", "http://www.ncbi.nlm.nih.gov/pubmed/15371533" ], "ideal_answer": [ "TIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress. The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD). Truncation mutants lacking the PRD domain do not induce spontaneous SGs and are not recruited to arsenite-induced SGs, whereas the PRD forms aggregates that are recruited to SGs in low-level-expressing cells but prevent SG assembly in high-level-expressing cells." ], "exact_answer": [ "The glutamine-rich prion-related domain (PRD)" ], "type": "factoid", "id": "56cdf4875795f9a73e000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Tia1/Pub1 is a stress granule component carrying a Q/N-rich prion domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24981173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18775331", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 490, "text": "We report an unanticipated link between stress granules and the serine/threonine kinase RSK2. In stressed breast cells, endogenous RSK2 colocalizes in granules with TIA-1 and poly(A)-binding protein 1, and the sequestration of RSK2 and TIA-1 exhibits codependency. The RSK2 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18775331", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Stress granule assembly is mediated by prion-like aggregation of TIA-1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 596, "text": "TIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress. The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD). Truncation mutants lacking the PRD domain do not induce spontaneous SGs and are not recruited to arsenite-induced SGs, whereas the PRD forms aggregates that are recruited to SGs in low-level-expressing cells but prevent SG assembly in high-level-expressing cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 1078, "text": "The PRD of TIA-1 exhibits many characteristics of prions: concentration-dependent aggregation that is inhibited by the molecular chaperone heat shock protein (HSP)70; resistance to protease digestion; sequestration of HSP27, HSP40, and HSP70; and induction of HSP70, a feedback regulator of PRD disaggregation. Substitution of the PRD with the aggregation domain of a yeast prion, SUP35-NM, reconstitutes SG assembly, confirming that a prion domain can mediate the assembly of SGs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "abstract" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1421, "text": "Our results reveal that prion-like aggregation of TIA-1 regulates SG formation downstream of eIF2alpha phosphorylation in response to stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Stress granule assembly is mediated by prion-like aggregation of TIA-1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": " TIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress. The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "abstract" } ] }, { "body": "Is the protein product of the cylindromatosis gene (CYLD) a deubiquitinating enzyme?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21283724", "http://www.ncbi.nlm.nih.gov/pubmed/17925880", "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "http://www.ncbi.nlm.nih.gov/pubmed/17495026", "http://www.ncbi.nlm.nih.gov/pubmed/20644164", "http://www.ncbi.nlm.nih.gov/pubmed/21931165", "http://www.ncbi.nlm.nih.gov/pubmed/12917689", "http://www.ncbi.nlm.nih.gov/pubmed/23066153", "http://www.ncbi.nlm.nih.gov/pubmed/17765686", "http://www.ncbi.nlm.nih.gov/pubmed/21728169", "http://www.ncbi.nlm.nih.gov/pubmed/20836156", "http://www.ncbi.nlm.nih.gov/pubmed/16900776", "http://www.ncbi.nlm.nih.gov/pubmed/17392286", "http://www.ncbi.nlm.nih.gov/pubmed/17053834", "http://www.ncbi.nlm.nih.gov/pubmed/19893491", "http://www.ncbi.nlm.nih.gov/pubmed/22406061", "http://www.ncbi.nlm.nih.gov/pubmed/21109933", "http://www.ncbi.nlm.nih.gov/pubmed/18643924", "http://www.ncbi.nlm.nih.gov/pubmed/18245814", "http://www.ncbi.nlm.nih.gov/pubmed/18497946", "http://www.ncbi.nlm.nih.gov/pubmed/21573132", "http://www.ncbi.nlm.nih.gov/pubmed/20227366" ], "ideal_answer": [ "CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling. ", "The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. The deubiquitinating enzyme CYLD has been identified as a key negative regulator for NF-kappaB. ", "The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis, an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor \u03baB (NF-\u03baB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-\u03baB activating proteins.", "Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling.CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Loss of the deubiquitinating activity of CYLD is correlated with tumorigenesis." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/SSEL_SALTI", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004843", "http://www.uniprot.org/uniprot/SSEL_SALCH", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016579", "http://www.uniprot.org/uniprot/SSEL_SALPA", "http://www.uniprot.org/uniprot/SSEL_SALPB", "http://www.uniprot.org/uniprot/CYLD_PONAB" ], "type": "yesno", "id": "550aef0ec2af5d5b7000000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas. The CYLD protein is a deubiquitinating enzyme that acts as a negative regulator of NF-\u03baB and JNK signaling through its interaction with NEMO and TNFR-associated factor 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23066153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-\u03baB) pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "CYLD is a lysine 63-deubiquitinating enzyme that inhibits NF-\u03baB and JNK signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Tumor suppressor gene CYLD is a deubiquitinating enzyme which negatively regulates various signaling pathways by removing the lysine 63-linked polyubiquitin chains from several specific substrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21573132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21283724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 426, "text": "The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis (Brooke-Spiegler syndrome), an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor \u03baB (NF-\u03baB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-\u03baB activating proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109933", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 470, "text": "Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20227366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19893491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Cyld encodes a 956-amino acid deubiquitinating enzyme (CYLD), which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412431", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 498, "text": "The deubiquitinating enzyme CYLD has been identified as a key negative regulator for NF-kappaB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18643924", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 424, "text": "CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Loss of the deubiquitinating activity of CYLD is correlated with tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18497946", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 794, "text": "We show that dCYLD encodes a deubiquitinating enzyme that deubiquitinates dTRAF2 and prevents dTRAF2 from ubiquitin-mediated proteolytic degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17765686", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 298, "text": "The CYLD gene encodes a deubiquitinating enzyme that removes Lys-63-linked ubiquitin chains from I kappa B kinase signaling components and thereby inhibits NF-kappaB pathway activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17495026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 415, "text": "Deubiquitinating enzymes (DUB) form a family of cysteine proteases that digests ubiquitin chains and reverses the process of protein ubiquitination. Despite the identification of a large number of DUBs, their physiological functions remain poorly defined. Here we provide genetic evidence that CYLD, a recently identified DUB, plays a crucial role in regulating the peripheral development and activation of B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17392286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "The cylindromatosis (CYLD) gene was originally identified as a tumor suppressor that is mutated in familial cylindromatosis, an autosomal dominant condition that confers a predisposition to multiple tumors of the skin appendages. CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Therefore, loss of CYLD function correlates with tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16900776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-\u03baB signaling pathway and attenuates NF-\u03baB and JNK signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20836156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The cylindromatosis tumor suppressor gene (Cyld) encodes a deubiquitinating enzyme (CYLD) with immunoregulatory function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644164", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 292, "text": "The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19893491", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 287, "text": "Here, we examined the potential role of the deubiquitinating enzyme CYLD (cylindromatosis), mutation of which has been reported to cause familial cylindromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18245814", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 530, "text": "The deubiquitinating enzyme cylindromatosis (CYLD), loss of which was originally reported to cause a benign human syndrome called cylindromatosis, has been identified as a key negative regulator for NF-kappaB in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17925880", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 293, "text": "The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19893491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-\ufffdB signaling pathway and attenuates NF-\ufffdB and JNK signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20836156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Cylindromatosis (CYLD) is a deubiquitinating enzyme that is altered in patients with familial cylindromatosis, a condition characterized by numerous benign adnexal tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17053834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12917689", "endSection": "title" }, { "offsetInBeginSection": 292, "offsetInEndSection": 468, "text": "Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20227366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-\u03baB signaling pathway and attenuates NF-\u03baB and JNK signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20836156", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 292, "text": "The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19893491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The cylindromatosis tumor suppressor gene (Cyld) encodes a deubiquitinating enzyme (CYLD) with immunoregulatory function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-\u03baB signaling pathway and attenuates NF-\u03baB and JNK signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20836156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The cylindromatosis tumor suppressor gene (Cyld) encodes an enzyme (CYLD) with deubiquitinating activity that has been implicated in the regulation of thymocyte selection in an NF-\u03baB-essential-modulator (NEMO)-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21728169", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 469, "text": "Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20227366", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 424, "text": "CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor \u03baB (NF-\u03baB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-\u03baB activating proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109933", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 343, "text": "CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18497946", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 287, "text": "Here, we examined the potential role of the deubiquitinating enzyme CYLD (cylindromatosis), mutation of which has been reported to cause familial cylindromatosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18245814", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 333, "text": "CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16900776", "endSection": "abstract" } ] }, { "body": "What is the characteristic domain of histone methyltransferases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20084102", "http://www.ncbi.nlm.nih.gov/pubmed/16292313", "http://www.ncbi.nlm.nih.gov/pubmed/17355966", "http://www.ncbi.nlm.nih.gov/pubmed/18693240", "http://www.ncbi.nlm.nih.gov/pubmed/17259630", "http://www.ncbi.nlm.nih.gov/pubmed/15939934", "http://www.ncbi.nlm.nih.gov/pubmed/16519522", "http://www.ncbi.nlm.nih.gov/pubmed/12628190", "http://www.ncbi.nlm.nih.gov/pubmed/20599755", "http://www.ncbi.nlm.nih.gov/pubmed/12398767", "http://www.ncbi.nlm.nih.gov/pubmed/14522075", "http://www.ncbi.nlm.nih.gov/pubmed/23453808", "http://www.ncbi.nlm.nih.gov/pubmed/14633678", "http://www.ncbi.nlm.nih.gov/pubmed/12372304", "http://www.ncbi.nlm.nih.gov/pubmed/15933069", "http://www.ncbi.nlm.nih.gov/pubmed/21124902", "http://www.ncbi.nlm.nih.gov/pubmed/19187761", "http://www.ncbi.nlm.nih.gov/pubmed/23652029", "http://www.ncbi.nlm.nih.gov/pubmed/12389038", "http://www.ncbi.nlm.nih.gov/pubmed/15659850", "http://www.ncbi.nlm.nih.gov/pubmed/17338551", "http://www.ncbi.nlm.nih.gov/pubmed/12514135", "http://www.ncbi.nlm.nih.gov/pubmed/17517655", "http://www.ncbi.nlm.nih.gov/pubmed/10949293", "http://www.ncbi.nlm.nih.gov/pubmed/16055700", "http://www.ncbi.nlm.nih.gov/pubmed/12887887", "http://www.ncbi.nlm.nih.gov/pubmed/21196496", "http://www.ncbi.nlm.nih.gov/pubmed/21564555" ], "ideal_answer": [ "SET (suppressor of variegation, enhancer of zest and trithorax) domain" ], "exact_answer": [ "SET domain" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011495", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042054", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011484" ], "type": "factoid", "id": "532dcfc9d6d3ac6a34000021", "snippets": [ { "offsetInBeginSection": 123, "offsetInEndSection": 185, "text": "C-terminal SET domain that catalyzes methylation of histone H3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652029", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 883, "text": "not all members of the H3K4 methyltransferase family contain n-SET domains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23453808", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 377, "text": "protein methyltransferases (both protein arginine and lysine methyltransferases) and the relatedness of their catalytic domains. We identified 51 protein lysine methyltransferase proteins based on similarity to the canonical Drosophila Su(var)3-9, enhancer of zeste (E(z)), and trithorax (trx) domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21564555", "endSection": "abstract" }, { "offsetInBeginSection": 41, "offsetInEndSection": 81, "text": " a SET domain histone methyltransferase ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196496", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 338, "text": "A common feature of the mammalian MLL/SET1 complexes is the presence of three core components (RbBP5, Ash2L and WDR5) and a catalytic subunit containing a SET domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21124902", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 308, "text": "catalytic histone methyltransferase SET-domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599755", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 103, "text": "SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20084102", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 261, "text": "The biological function of MLL1 is mediated by the histone H3K4 methyltransferase activity of the carboxyl-terminal SET domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19187761", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 336, "text": "Polycomb repressive complex 2 (PRC2), which methylates lysine 27 of histone H3. Information on how PRC2 works is limited by lack of structural data on the catalytic subunit, Enhancer of zeste (E(Z)), and the paucity of E(z) mutant alleles that alter its SET domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18693240", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 314, "text": "histone modification is catalyzed by protein lysine methyltransferases (PKMTs). PKMTs contain a conserved SET domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17517655", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 129, "text": "Set1A complex analogous to the yeast Set1/COMPASS histone H3-Lys4 methyltransferase complex ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17355966", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 318, "text": "Set1A protein shares 39% identity with an uncharacterized SET domain protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17355966", "endSection": "abstract" }, { "offsetInBeginSection": 45, "offsetInEndSection": 117, "text": "multiple methylations catalyzed by SET domain protein methyltransferases", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17338551", "endSection": "title" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1261, "text": "methyl group transfers by SET domain protein lysine methyltransferases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17338551", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 70, "text": "SET domain protein functions as a histone methyltransferase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17259630", "endSection": "title" }, { "offsetInBeginSection": 1780, "offsetInEndSection": 1867, "text": "SUV39H1 impaired enzyme activity despite the presence of an intact catalytic SET domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16519522", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 217, "text": "Meisetz (meiosis-induced factor containing a PR/SET domain and zinc-finger motif) is a histone methyltransferase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16292313", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 327, "text": "The fly complex contains a catalytic SET domain subuni", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16055700", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 122, "text": "ESC-E(Z) complex of Drosophila melanogaster Polycomb group (PcG) repressors is a histone H3 methyltransferase (HMTase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16055700", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 295, "text": "Murine G9a is a 1263 amino acid H3-K9 methyltransferase that possesses characteristic SET domain and ANK repeats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15939934", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 665, "text": "domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15933069", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 200, "text": "SET domain, first identified within and named after proteins encoded by three Drosophila genes [Su(var)3-9, E(z), and Trithorax], is recognized as a signature motif for histone methyltransferases ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15659850", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 160, "text": "(HMT)(1) class enzymes that methylate lysine residues of histones or proteins contain a conserved catalytic core termed the SET domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14633678", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 162, "text": "ERG-associated protein with a SET domain, also called SETDB1) is a novel histone methyltransferase that catalyzes methylation of histone H3-lysine 9 (H3-K9)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14522075", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 136, "text": "SET domain histone methyltransferase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12887887", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 198, "text": " Unlike other histone methyltransferases, Dot1 does not contain a SET domain,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12628190", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 966, "text": "SET domain-containing HMTase ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12514135", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 331, "text": "SET (suppressor of variegation, enhancer of zest and trithorax) domain (ESET) that was found to have the activity of a histone H3-specific methyltransferase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12398767", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 150, "text": "SET domain contains the catalytic center of lysine methyltransferases that target the N-terminal tails of histones and regulate chromatin function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12389038", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 289, "text": " The evolutionarily conserved SET domain occurs in most proteins known to possess histone lysine methyltransferase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12372304", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 746, "text": "the evolutionarily conserved SET domain, which requires adjacent cysteine-rich regions to confer histone methyltransferase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10949293", "endSection": "abstract" } ] }, { "body": "What is smFISH?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26098021", "http://www.ncbi.nlm.nih.gov/pubmed/23433107" ], "ideal_answer": [ "smFISH (Single-molecule fluorescence in situ hybridization) allows for quantitative imaging of single RNA molecules. Multi-color, single-molecule fluorescence in situ hybridization (smFISH) is particularly useful since it enables analysis of several different transcripts simultaneously. Combining smFISH with immunofluorescent protein detection provides additional information about the association between transcription level, cellular localization, and protein expression in individual cells." ], "type": "summary", "id": "56af5abb0a360a5e45000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Single-molecule fluorescence in situ hybridization: quantitative imaging of single RNA molecules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23433107", "endSection": "title" }, { "offsetInBeginSection": 491, "offsetInEndSection": 1197, "text": "In situ hybridization-based analysis methods complement these studies by providing information about how expression levels change between cells within normal and diseased tissues, and they provide information about the localization of transcripts within cells, which is important in understanding mechanisms of gene regulation. Multi-color, single-molecule fluorescence in situ hybridization (smFISH) is particularly useful since it enables analysis of several different transcripts simultaneously. Combining smFISH with immunofluorescent protein detection provides additional information about the association between transcription level, cellular localization, and protein expression in individual cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23433107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "We combine immunofluorescence and single-molecule fluorescence in situ hybridization (smFISH), followed by automated image analysis, to quantify the concentration of nuclear transcription factors, number of transcription factors bound, and number of nascent mRNAs synthesized at individual gene loci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26098021", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1201, "text": "Multi-color, single-molecule fluorescence in situ hybridization (smFISH) is particularly useful since it enables analysis of several different transcripts simultaneously. Combining smFISH with immunofluorescent protein detection provides additional information about the association between transcription level, cellular localization, and protein expression in individual cells. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23433107", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 1198, "text": "Multi-color, single-molecule fluorescence in situ hybridization (smFISH) is particularly useful since it enables analysis of several different transcripts simultaneously. Combining smFISH with immunofluorescent protein detection provides additional information about the association between transcription level, cellular localization, and protein expression in individual cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23433107", "endSection": "abstract" } ] }, { "body": "Which are the bioinformatics tools for gene structure prediction?\n", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15980556", "http://www.ncbi.nlm.nih.gov/pubmed/15564294", "http://www.ncbi.nlm.nih.gov/pubmed/19329068", "http://www.ncbi.nlm.nih.gov/pubmed/21056007", "http://www.ncbi.nlm.nih.gov/pubmed/15608279", "http://www.ncbi.nlm.nih.gov/pubmed/9521933", "http://www.ncbi.nlm.nih.gov/pubmed/7584460", "http://www.ncbi.nlm.nih.gov/pubmed/10487869", "http://www.ncbi.nlm.nih.gov/pubmed/18801175", "http://www.ncbi.nlm.nih.gov/pubmed/16963498", "http://www.ncbi.nlm.nih.gov/pubmed/14654703", "http://www.ncbi.nlm.nih.gov/pubmed/11337482", "http://www.ncbi.nlm.nih.gov/pubmed/15784153", "http://www.ncbi.nlm.nih.gov/pubmed/14764557", "http://www.ncbi.nlm.nih.gov/pubmed/10764574", "http://www.ncbi.nlm.nih.gov/pubmed/22537006", "http://www.ncbi.nlm.nih.gov/pubmed/16772025", "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "http://www.ncbi.nlm.nih.gov/pubmed/18801164", "http://www.ncbi.nlm.nih.gov/pubmed/15374869", "http://www.ncbi.nlm.nih.gov/pubmed/20726803" ], "ideal_answer": [ "The in silico prediction of the complete structure of genes is one of the main challenges of bioinformatics. A critical part in the gene structure prediction is to identify the boundaries between exons and introns (i.e. splice sites) in the coding region. Several advanced bioinformatics tools have been developed for the precise delineation of a given gene structure: WPSS, SCGPred, TICO, GLIMMER, MetWAMer, WebScipio, GeneSeqer, SplicePredictor, DGSplicer, Transcript Assembly Program (TAP), GeneBuilder, SeqHelp, HSPL, RNASPL, HEXON, CDSB, HBR, FGENE and FGENEH for human genes.", "SCGPred: a score-based method for gene structure prediction by combining multiple sources of evidence. MetWAMer.gthXML is a special-purpose variant of the software, specifically tailored to refine gene structure predictions generated by the GenomeThreader [30] and GeneSeqer [31] programs for spliced alignment-based gene structure annotation. WebScipio: an online tool for the determination of gene structures using protein sequences. " ], "exact_answer": [ [ "WPSS" ], [ "SCGPred" ], [ "TICO" ], [ "GLIMMER" ], [ "MetWAMer" ], [ "WebScipio" ], [ "GeneSeqer" ], [ "SplicePredictor" ], [ "DGSplicer" ], [ "TAP" ], [ "GeneBuilder" ], [ "SeqHelp" ], [ "FGENE", "FGENEH" ], [ "HSPL" ], [ "RNASPL" ], [ "HEXON" ], [ "CDSB" ], [ "HBR" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "list", "id": "51740da48ed59a060a000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 515, "text": "The prediction of the complete structure of genes is one of the very important tasks of bioinformatics, especially in eukaryotes. A crucial part in the gene structure prediction is to determine the splice sites in the coding region. Identification of splice sites depends on the precise recognition of the boundaries between exons and introns of a given DNA sequence. This problem can be formulated as a classification of sequence elements into 'exon-intron' (EI), 'intron-exon' (IE) or 'None' (N) boundary classes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21056007", "endSection": "sections.0" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1014, "text": "The proposed WPSS method poses efficient results compared with the performance of many methods proposed in the literature.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21056007", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "SCGPred: a score-based method for gene structure prediction by combining multiple sources of evidence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329068", "endSection": "title" }, { "offsetInBeginSection": 267, "offsetInEndSection": 561, "text": "Moreover, computational gene finding in newly sequenced genomes is especially a difficult task due to the absence of a training set of abundant validated genes. Here we present a new gene-finding program, SCGPred, to improve the accuracy of prediction by combining multiple sources of evidence.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329068", "endSection": "sections.0" }, { "offsetInBeginSection": 1088, "offsetInEndSection": 1260, "text": "Therefore, SCG-Pred can serve as an alternative gene-finding tool for newly sequenced eukaryotic genomes. The program is freely available at http://bio.scu.edu.cn/SCGPred/.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329068", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Incorporation of splice site probability models for non-canonical introns improves gene structure prediction in plants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "endSection": "title" }, { "offsetInBeginSection": 704, "offsetInEndSection": 960, "text": "We pursued one such approach and describe the training and implementation of GC-donor splice site models for Arabidopsis and rice, with the goal of exploring whether specific modeling of non-canonical introns can enhance gene structure prediction accuracy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "endSection": "sections.0" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 2144, "text": "Source code for the updated versions of GeneSeqer and SplicePredictor (distributed with the GeneSeqer code) isavailable at http://bioinformatics.iastate.edu/bioinformatics2go/gs/download.html. Web servers for Arabidopsis, rice and other plant species are accessible at http://www.plantgdb.org/PlantGDB-cgi/GeneSeqer/AtGDBgs.cgi, http://www.plantgdb.org/PlantGDB-cgi/GeneSeqer/OsGDBgs.cgi and http://www.plantgdb.org/PlantGDB-cgi/GeneSeqer/PlantGDBgs.cgi, respectively. A SplicePredictor web server is available at http://bioinformatics.iastate.edu/cgi-bin/sp.cgi. Software to generate training data and parameterizations for Bayesian splice site models is available at http://gremlin1.gdcb.iastate.edu/~volker/SB05B/BSSM4GSQ/", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Prediction of splice sites with dependency graphs and their expanded bayesian networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15374869", "endSection": "title" }, { "offsetInBeginSection": 283, "offsetInEndSection": 427, "text": "A crucial part in the gene structure prediction is to determine the precise exon-intron boundaries, i.e. the splice sites, in the coding region.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15374869", "endSection": "sections.0" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1441, "text": "Software (a program called DGSplicer) and datasets used are available at http://csrl.ee.nthu.edu.tw/bioinf/ BACKGROUND: cclu@ee.nthu.edu.tw.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15374869", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Gene structure prediction from consensus spliced alignment of multiple ESTs matching the same genomic locus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14764557", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 98, "text": "Accurate gene structure annotation is a challenging computational problem in genomics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14764557", "endSection": "sections.0" }, { "offsetInBeginSection": 1998, "offsetInEndSection": 2181, "text": "The splice site prediction tool (SplicePredictor) is distributed with the GeneSeqer code. A SplicePredictor web server is available at http://bioinformatics.iastate.edu/cgi-bin/sp.cgi", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14764557", "endSection": "sections.0" }, { "offsetInBeginSection": 352, "offsetInEndSection": 491, "text": "We have developed a software tool, Transcript Assembly Program (TAP), to delineate gene structures using genomically aligned EST sequences.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11337482", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "GeneBuilder: interactive in silico prediction of gene structure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10487869", "endSection": "title" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1556, "text": "In the case of low homology, GeneBuilder is still able to predict the gene structure. The GeneBuilder system has been tested by using the standard set (Burset and Guigo, Genomics, 34, 353-367, 1996) and the performances are: 0.89 sensitivity and 0.91 specificity at the nucleotide level.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10487869", "endSection": "sections.0" }, { "offsetInBeginSection": 138, "offsetInEndSection": 367, "text": "The computer program SeqHelp organizes information from database searches, gene structure prediction, and other information to generate multiply aligned, hypertext-linked reports to allow for fast analysis of molecular sequences.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9521933", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Identification of human gene structure using linear discriminant functions and dynamic programming.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7584460", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Development of advanced technique to identify gene structure is one of the main challenges of the Human Genome Project.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7584460", "endSection": "sections.0" }, { "offsetInBeginSection": 369, "offsetInEndSection": 469, "text": "A gene structure prediction system FGENE has been developed based on the exon recognition functions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7584460", "endSection": "sections.0" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1755, "text": "Analysis of uncharacterized human sequences based on our methods for splice site (HSPL, RNASPL), internal exons (HEXON), all type of exons (FEXH) and human (FGENEH) and bacterial (CDSB) gene structure prediction and recognition of human and bacterial sequences (HBR) (to test a library for E. coli contamination) is available through the University of Houston, Weizmann Institute of Science network server and a WWW page of the Human Genome Center at Baylor College of Medicine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7584460", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "In the bioinformatics field, many computer algorithmic and data mining technologies have been developed for gene prediction, protein-protein interaction analysis, sequence analysis, and protein folding predictions, to name a few.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20726803", "endSection": "sections.0" }, { "offsetInBeginSection": 142, "offsetInEndSection": 267, "text": "The accurate prediction of intron boundaries largely facilitates the correct prediction of gene structure in nuclear genomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15564294", "endSection": "sections.0" } ] }, { "body": "Which is the major phytoalexin in alfalfa (Medicago sativa L.)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1912490", "http://www.ncbi.nlm.nih.gov/pubmed/19343413", "http://www.ncbi.nlm.nih.gov/pubmed/16667295", "http://www.ncbi.nlm.nih.gov/pubmed/24226375", "http://www.ncbi.nlm.nih.gov/pubmed/7625843", "http://www.ncbi.nlm.nih.gov/pubmed/16667691", "http://www.ncbi.nlm.nih.gov/pubmed/9484461" ], "ideal_answer": [ "The major phytoalexin in alfalfa (Medicago sativa L.) is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin. Medicarpin is synthesized via the isoflavonoid branch of phenylpropanoid metabolism." ], "exact_answer": [ "medicarpin" ], "concepts": [ "http://www.biosemantics.org/jochem#4252976", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0052315", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000455" ], "type": "factoid", "id": "5543829fed966d112c000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Medicarpin, the major phytoalexin in alfalfa, is synthesized via the isoflavonoid branch of phenylpropanoid metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9484461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Medicarpin, the major phytoalexin in alfalfa, is synthesized by way of the isoflavonoid branch of phenylpropanoid metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7625843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The major phytoalexin in alfalfa is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1912490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "The isoflavonoid conjugates medicarpin-3-O-glucoside-6-O-malonate (MGM), afrormosin-7-O-glucoside (AG), and afrormosin-7-O-glucoside-6-O-malonate (AGM) were isolated and characterized from cell suspension cultures of alfalfa (Medicago sativa L.), where they were the major constitutive secondary metabolites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16667691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Alfalfa (Medicago sativa L.) cell suspension cultures accumulated high concentrations of the pterocarpan phytoalexin medicarpin, reaching a maximum within 24 hours after exposure to an elicitor preparation from cell walls of the phytopathogenic fungus Colletotrichum lindemuthianum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16667295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "The isoflavonoid conjugates medicarpin-3-O-glucoside-6''-O-malonate (MGM), afrormosin-7-O-glucoside (AG), and afrormosin-7-O-glucoside-6''-O-malonate (AGM) were isolated and characterized from cell suspension cultures of alfalfa (Medicago sativa L.), where they were the major constitutive secondary metabolites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16667691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The major phytoalexin in alfalfa is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1912490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Medicarpin, the major phytoalexin in alfalfa, is synthesized via the isoflavonoid branch of phenylpropanoid metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9484461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Medicarpin, the major phytoalexin in alfalfa, is synthesized by way of the isoflavonoid branch of phenylpropanoid metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7625843", "endSection": "abstract" } ] }, { "body": "What is the correlation between SPARC expression and growth inhibition in human cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21799470", "http://www.ncbi.nlm.nih.gov/pubmed/20087345", "http://www.ncbi.nlm.nih.gov/pubmed/16424866", "http://www.ncbi.nlm.nih.gov/pubmed/19830689", "http://www.ncbi.nlm.nih.gov/pubmed/22863973", "http://www.ncbi.nlm.nih.gov/pubmed/20215880", "http://www.ncbi.nlm.nih.gov/pubmed/22206672", "http://www.ncbi.nlm.nih.gov/pubmed/20100207", "http://www.ncbi.nlm.nih.gov/pubmed/12414657", "http://www.ncbi.nlm.nih.gov/pubmed/15958556", "http://www.ncbi.nlm.nih.gov/pubmed/19920824", "http://www.ncbi.nlm.nih.gov/pubmed/23321672", "http://www.ncbi.nlm.nih.gov/pubmed/19236378", "http://www.ncbi.nlm.nih.gov/pubmed/21098700", "http://www.ncbi.nlm.nih.gov/pubmed/12500936", "http://www.ncbi.nlm.nih.gov/pubmed/20955243" ], "ideal_answer": [ "Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell-cell and cell-matrix interactions. SPARC seems to act as a tumour suppressor, as it has been found that loss of SPARC accelerates the development of certain types of cancer, whereas its expression impairs tumor growth. However it has also been associated with a aggressive phenotypes of some tumours. The role of SPARC may depend on its subcellular localization." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045926", "http://www.uniprot.org/uniprot/SPRC_HUMAN" ], "type": "summary", "id": "517151f28ed59a060a000008", "snippets": [ { "offsetInBeginSection": 264, "offsetInEndSection": 535, "text": "Using a chemical carcinogenesis model in Sparc-deficient mice and their wild-type littermates, we found that loss of SPARC accelerated the development of urothelial preneoplasia (atypia and dysplasia), neoplasia, and metastasis and was associated with decreased survival.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23321672", "endSection": "sections.0" }, { "offsetInBeginSection": 683, "offsetInEndSection": 1003, "text": "Our studies showed that inhibition of HDAC decreased NB proliferation, and induced caspase activity and G1 growth arrest. Expression patterns of cancer-related genes were modulated by VPA. The expression of THBS1, CASP8, SPARC, CDKN1A, HIC1, CDKN1B, and HIN1 was upregulated, and that of MYCN and TIG1 was downregulated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863973", "endSection": "sections.0" }, { "offsetInBeginSection": 325, "offsetInEndSection": 424, "text": "In this study, we demonstrate that expression of SPARC inhibits medulloblastoma cell proliferation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22206672", "endSection": "sections.0" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1437, "text": "Concomitantly, SPARC was upregulated in all ccRCC cells, suggesting that Ukrain could also affect cell proliferation by cell cycle inhibition, as supported by the cell cycle analysis, as SPARC also acts as a cell cycle inhibitor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21799470", "endSection": "sections.0" }, { "offsetInBeginSection": 470, "offsetInEndSection": 770, "text": "SPARC silencing in IM-R cells restored imatinib sensitivity, whereas enforced SPARC expression in imatinib-sensitive cells promoted viability as well as protection against imatinib-mediated apoptosis. Notably, we found that the protective effect of SPARC required intracellular retention inside cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098700", "endSection": "sections.0" }, { "offsetInBeginSection": 455, "offsetInEndSection": 667, "text": "We found that depletion of SPARC induces G2/M cell cycle arrest and tumor growth inhibition with activation of p53 and induction of p21(Cip1/Waf1) acting as a checkpoint, preventing efficient mitotic progression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20955243", "endSection": "sections.0" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1413, "text": "Knockdown of SPARC expression in H322 and A549 cells led to suppression of cell invasion, comparable to that observed in KLF4-transfected cells. Moreover, retrovirus-mediated restoration of SPARC expression in KLF4-transfected cells abrogated KLF4-induced anti-invasion activity. Together, our results indicate that KLF4 inhibits lung cancer cell invasion by suppressing SPARC gene expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20215880", "endSection": "sections.0" }, { "offsetInBeginSection": 256, "offsetInEndSection": 953, "text": "To validate the potential of SPARC as a therapeutic target, we examined the effect of the knockdown of SPARC with SPARC-specific siRNA on the growth of human melanoma cell lines. SPARC siRNAs exerted a potent knockdown effect. Silencing of SPARC resulted in growth inhibition with G(1) arrest accompanied by accumulation of p21, a G(1) cyclin-dependent kinase inhibitor, in MeWo and CRL1579 cells. Moreover, the induction of p53 was observed in MeWo cells, but not in CRL1579 cells. Conditioned media containing SPARC from MeWo cells could not restore the growth of SPARC-silenced MeWo cells. This result suggests that intracellular SPARC, but not secreted SPARC, is involved in cell proliferation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100207", "endSection": "sections.0" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1791, "text": "In vivo experiments revealed that SPARC overexpression in HCC cells inhibited their tumorigenic capacity and increased animal survival through a mechanism that partially involves host macrophages. Our data suggest that SPARC overexpression in HCC cells results in a reduced tumorigenicity partially through the induction of mesenchymal-to-epithelial transition (MET).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830689", "endSection": "sections.0" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1345, "text": "Finally, we demonstrated that SPARC, which has been previously associated with meningioma invasiveness, was increased in aggressive meningiomas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19236378", "endSection": "sections.0" }, { "offsetInBeginSection": 291, "offsetInEndSection": 824, "text": "We found that the leukemic cells of AML patients with MLL gene rearrangements express low to undetectable amounts of SPARC whereas normal hematopoietic progenitors and most AML patients express this gene. SPARC RNA and protein levels were also low or undetectable in AML cell lines with MLL translocations. Consistent with its tumor suppressive effects in various solid tumor models, exogenous SPARC protein selectively reduced the growth of cell lines with MLL rearrangements by inhibiting cell cycle progression from G1 to S phase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16424866", "endSection": "sections.0" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1252, "text": "These data indicate that SPARC plays an essential role in tumor evasion from immune surveillance through the inhibition of the antitumor PMN activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15958556", "endSection": "sections.0" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1801, "text": "We conclude that SPARC is inhibitory to human breast cancer cell proliferation, and does not stimulate migration, in contrast to its stimulatory effects reported for melanoma (proliferation and migration) and glioma (migration) cells. Similar growth repression by SPARC has been reported for ovarian cancer cells, and this may be a common feature among carcinomas.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12500936", "endSection": "sections.0" }, { "offsetInBeginSection": 2345, "offsetInEndSection": 2508, "text": "Furthermore, SPARC delayed but did not inhibit tumor growth. The patterns of invasion and the extent of growth delay correlated with the level of SPARC expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12414657", "endSection": "sections.0" } ] }, { "body": "Which syndrome is associated with mutations in the LYST gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9070932", "http://www.ncbi.nlm.nih.gov/pubmed/25551669", "http://www.ncbi.nlm.nih.gov/pubmed/8717042", "http://www.ncbi.nlm.nih.gov/pubmed/24112114", "http://www.ncbi.nlm.nih.gov/pubmed/21488161", "http://www.ncbi.nlm.nih.gov/pubmed/18043242", "http://www.ncbi.nlm.nih.gov/pubmed/16791600", "http://www.ncbi.nlm.nih.gov/pubmed/23804531", "http://www.ncbi.nlm.nih.gov/pubmed/15896657", "http://www.ncbi.nlm.nih.gov/pubmed/24072239", "http://www.ncbi.nlm.nih.gov/pubmed/24521565", "http://www.ncbi.nlm.nih.gov/pubmed/20458667", "http://www.ncbi.nlm.nih.gov/pubmed/23521865", "http://www.ncbi.nlm.nih.gov/pubmed/10411929", "http://www.ncbi.nlm.nih.gov/pubmed/14993748", "http://www.ncbi.nlm.nih.gov/pubmed/10594238", "http://www.ncbi.nlm.nih.gov/pubmed/10648412", "http://www.ncbi.nlm.nih.gov/pubmed/20617205", "http://www.ncbi.nlm.nih.gov/pubmed/25582874", "http://www.ncbi.nlm.nih.gov/pubmed/22762706", "http://www.ncbi.nlm.nih.gov/pubmed/11984006", "http://www.ncbi.nlm.nih.gov/pubmed/16518687", "http://www.ncbi.nlm.nih.gov/pubmed/11854420", "http://www.ncbi.nlm.nih.gov/pubmed/10482950", "http://www.ncbi.nlm.nih.gov/pubmed/20368792" ], "ideal_answer": [ "Mutations in LYST, a gene encoding a putative lysosomal trafficking protein, cause Ch\u00e9diak-Higashi syndrome (CHS), an autosomal recessive disorder typically characterized by infantile-onset hemophagocytic syndrome and immunodeficiency, and oculocutaneous albinism. A small number of reports of rare, attenuated forms of CHS exist, with affected individuals exhibiting progressive neurodegenerative disease beginning in early adulthood with cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral neuropathy, as well as subtle pigmentary abnormalities and subclinical or absent immune dysfunction." ], "exact_answer": [ "Chediak-Higashi syndrome" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "factoid", "id": "56f564f909dd18d46b000009", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 642, "text": "Mutations in LYST, a gene encoding a putative lysosomal trafficking protein, cause Ch\u00e9diak-Higashi syndrome (CHS), an autosomal recessive disorder typically characterized by infantile-onset hemophagocytic syndrome and immunodeficiency, and oculocutaneous albinism. A small number of reports of rare, attenuated forms of CHS exist, with affected individuals exhibiting progressive neurodegenerative disease beginning in early adulthood with cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral neuropathy, as well as subtle pigmentary abnormalities and subclinical or absent immune dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23521865", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 436, "text": "Mutations in the CHS1 (LYST) gene result in CHS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15896657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by variable degrees of oculocutaneous albinism, recurrent infections, and a mild bleeding tendency, with late neurologic dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15896657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease resulting from mutations in the LYST/CHS1 gene, which encodes for a 429\u00a0kDa protein, CHS1/LYST, that regulates vesicle trafficking and determines the size of lysosomes and other organelles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24112114", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 482, "text": "Mutations in the CHS1 (LYST) gene result in CHS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15896657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Chediak-Higashi syndrome: novel mutation of the CHS1/LYST gene in 3 Omani patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072239", "endSection": "title" }, { "offsetInBeginSection": 463, "offsetInEndSection": 576, "text": "The CHS1/LYST gene was identified over 10 years ago and homologous CHS1/LYST genes are present in all eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18043242", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 435, "text": "We report a novel nonsense mutation of the CHS1/LYST gene in 3 Omani patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072239", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "A novel single point mutation of the LYST gene in two siblings with different phenotypic features of Chediak Higashi syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21488161", "endSection": "title" }, { "offsetInBeginSection": 736, "offsetInEndSection": 1309, "text": "Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the \u03b2-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25582874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Cloning of bovine LYST gene and identification of a missense mutation associated with Chediak-Higashi syndrome of cattle", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10594238", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "A frameshift mutation in the LYST gene is responsible for the Aleutian color and the associated Ch\u00e9diak-Higashi syndrome in American mink", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22762706", "endSection": "title" }, { "offsetInBeginSection": 355, "offsetInEndSection": 714, "text": "Disease-causing mutations in the genes encoding perforin (PRF1, FHL2), munc13-4 (UNC13D, FHL3), syntaxin 11 (STX11, FHL4), and munc18-2 (UNC18-2/STXBP2, FHL5) have been previously identified in Familial Hemophagocyic Lymphohistiocytosis (FHL), whereas mutation in RAB27A and LYST account for Griscelli syndome type 2 and Chediak-Higashi syndrome, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20458667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease resulting from mutations in the LYST/CHS1 gene, which encodes for a 429\u00a0kDa protein, CHS1/LYST, that regulates vesicle trafficking and determines the size of lysosomes and other organelles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24112114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Chediak-Higashi syndrome is a genetic disorder caused by mutations in a gene encoding a protein named LYST in humans ("lysosomal trafficking regulator") or Beige in mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854420", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 392, "text": "The Chediak-Higashi syndrome (CHS), a life-threatening autosomal recessive disease with frequent mutations in the LYST gene, and its animal model, the beige mouse, are both characterized by lysosomal defects with accumulation of giant lysosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16791600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Cloning of bovine LYST gene and identification of a missense mutation associated with Chediak-Higashi syndrome of cattle.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10594238", "endSection": "title" }, { "offsetInBeginSection": 272, "offsetInEndSection": 431, "text": "These data are consistent with LYST being the gene for the human Chediak-Higashi Syndrome and strengthen the synteny relationship between MMU13 and human 1q43.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9070932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "A frameshift mutation in the LYST gene is responsible for the Aleutian color and the associated Ch\u00e9diak-Higashi syndrome in American mink.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22762706", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Infantile hemophagocytic lymphohistiocytosis in a case of chediak-higashi syndrome caused by a mutation in the LYST/CHS1 gene presenting with delayed umbilical cord detachment and diarrhea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25551669", "endSection": "title" }, { "offsetInBeginSection": 177, "offsetInEndSection": 340, "text": "Here, we describe two siblings with CHS due to a novel homozygous R1836X mutation in the LYST gene associated with loss of NK cell degranulation and cytotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21488161", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 1311, "text": "Parkin (PARK2) gene mutations are responsible for juvenile parkinsonism, and possible peripheral nervous system involvement has been reported. Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the \u03b2-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25582874", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 1386, "text": "Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the \u03b2-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations. This article reviews conditions in which PN may coexist with parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25582874", "endSection": "abstract" } ] }, { "body": "Has the presence of delayed enhancement been documented in athletes performing strenuous exercise?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22160404", "http://www.ncbi.nlm.nih.gov/pubmed/19427448", "http://www.ncbi.nlm.nih.gov/pubmed/22798307", "http://www.ncbi.nlm.nih.gov/pubmed/8902021", "http://www.ncbi.nlm.nih.gov/pubmed/24029371", "http://www.ncbi.nlm.nih.gov/pubmed/24326931", "http://www.ncbi.nlm.nih.gov/pubmed/19332846" ], "ideal_answer": [ "There are contrasting literature data on the presence of delayed enhancement, as a sign of myocardial fibrosis, in healthy athletes. More studies are necessary to define the presence, incidence and severity, as well clinical and prognostic meaning, of delayed enhancement magnetic resonance in healthy athletes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054874", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444" ], "type": "yesno", "id": "531d34be267d7dd053000004", "snippets": [ { "offsetInBeginSection": 1240, "offsetInEndSection": 1491, "text": "Atypical findings such as marked cardiac dilation, reduced deformation, or small patches of delayed gadolinium enhancement may be commonly encountered in well-trained athletes, but, at present, the prognostic significance of such findings is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029371", "endSection": "abstract" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1648, "text": "On CMR, DGE localized to the interventricular septum was identified in 5 of 39 athletes who had greater cumulative exercise exposure and lower RVEF (47.1 \u00b1 5.9 vs. 51.1 \u00b1 3.7%, P = 0.042) than those with normal CMR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22160404", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 912, "text": "Post-event cardiac MRI demonstrated the interval appearance of delayed enhancement of gadolinium at the inferior insertion of the right ventricle and in the interventricular septum-a novel finding that may represent subtle inflammation secondary to a combined exercise and altitude effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22798307", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1544, "text": "No evidence of delayed enhancement of the left ventricular myocardium was found on CMR imaging, suggesting that the increase in cardiac biomarkers after the marathon may not have be due to myocardial necrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19427448", "endSection": "abstract" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1891, "text": "Of the 102 runners, five had a CAD pattern of LGE, and seven had a non-CAD pattern of LGE. The CAD pattern of LGE was located in the territory of the left anterior descending coronary artery more frequently than was the non-CAD pattern (P = .0027, Fisher exact test). The prevalence of LGE in runners was higher than that in age-matched control subjects (12% vs 4%; P = .077, McNemar exact test).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19332846", "endSection": "abstract" } ] }, { "body": "How does dronedarone affect thyroid hormone signaling in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21442236", "http://www.ncbi.nlm.nih.gov/pubmed/17535870", "http://www.ncbi.nlm.nih.gov/pubmed/12538616", "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "http://www.ncbi.nlm.nih.gov/pubmed/12063079" ], "ideal_answer": [ "Dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor and selectively mimicks hypothyroidism.\nDronedarone decreases TRalpha 1 and beta 1 expression by about 50% in the right atrium (RA) while in the left ventricle, only TRbeta1 is found to be decreased." ], "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.biosemantics.org/jochem#4275394", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.biosemantics.org/jochem#4275389", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://www.biosemantics.org/jochem#4233556", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.biosemantics.org/jochem#4274245", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002154", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.biosemantics.org/jochem#4250045", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "summary", "id": "516d4770298dcd4e51000076", "snippets": [ { "offsetInBeginSection": 862, "offsetInEndSection": 980, "text": "Administration of debutyl-dronedarone (DBD), a TR\u03b11 antagonist abolished the T3-limiting effect on reperfusion injury:", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21442236", "endSection": "sections.0" }, { "offsetInBeginSection": 739, "offsetInEndSection": 846, "text": "Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870", "endSection": "sections.0" }, { "offsetInBeginSection": 847, "offsetInEndSection": 889, "text": "In the LVW, AM and Dron decreased TRbeta 1", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535870", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "endSection": "sections.0" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1478, "text": "dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15687816", "endSection": "sections.0" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1391, "text": "The in vitro and in vivo findings suggest that dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12538616", "endSection": "sections.0" }, { "offsetInBeginSection": 793, "offsetInEndSection": 925, "text": "Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12063079", "endSection": "sections.0" } ] }, { "body": "Name the factors required for selenoprotein synthesis in eukaryotes", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10809727", "http://www.ncbi.nlm.nih.gov/pubmed/15208449", "http://www.ncbi.nlm.nih.gov/pubmed/8898393", "http://www.ncbi.nlm.nih.gov/pubmed/19279205", "http://www.ncbi.nlm.nih.gov/pubmed/8614619", "http://www.ncbi.nlm.nih.gov/pubmed/20417644", "http://www.ncbi.nlm.nih.gov/pubmed/16782878", "http://www.ncbi.nlm.nih.gov/pubmed/19467292", "http://www.ncbi.nlm.nih.gov/pubmed/11839807", "http://www.ncbi.nlm.nih.gov/pubmed/10444382", "http://www.ncbi.nlm.nih.gov/pubmed/19223320", "http://www.ncbi.nlm.nih.gov/pubmed/17346238", "http://www.ncbi.nlm.nih.gov/pubmed/16230358", "http://www.ncbi.nlm.nih.gov/pubmed/14978508" ], "ideal_answer": [ "eFSec, SBP2, SECp43, PSTK, Sec synthase (Sec S, SLA/LP), SPS2 (SelD), tRNASec, SECIS element, (L30), SPS1" ], "exact_answer": [ [ "eFSec" ], [ "SBP2" ], [ "SECp43" ], [ "PSTK" ], [ "Sec synthase", "Sec S", "SLA/LP" ], [ "SPS2", "SelD" ], [ "tRNASec" ], [ "SECIS element" ], [ "(L30)" ], [ "SPS1" ] ], "type": "list", "id": "51766e438ed59a060a000031", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 323, "text": "The process requires the Sec insertion sequence (SECIS) element, tRNASec, and protein factors including the SECIS binding protein 2 (SBP2)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16782878", "endSection": "sections.0" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1392, "text": "Taken together, these data establish the role of SECp43 and SLA in selenoprotein biosynthesis through interaction with tRNA([Ser]Sec) in a multiprotein complex.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16230358", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Selenophosphate synthetase (SelD) generates the selenium donor for selenocysteine biosynthesis in eubacteria. One homologue of SelD in eukaryotes is SPS1 (selenophosphate synthetase 1) and a second one, SPS2, was identified as a selenoprotein in mammals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346238", "endSection": "sections.0" }, { "offsetInBeginSection": 838, "offsetInEndSection": 1063, "text": "These in vivo studies indicate that SPS2 is essential for generating the selenium donor for selenocysteine biosynthesis in mammals, whereas SPS1 probably has a more specialized, non-essential role in selenoprotein metabolism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346238", "endSection": "sections.0" } ] }, { "body": "What are the functions of the ESCRT machinery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25637630", "http://www.ncbi.nlm.nih.gov/pubmed/25624505", "http://www.ncbi.nlm.nih.gov/pubmed/24148098", "http://www.ncbi.nlm.nih.gov/pubmed/26339479", "http://www.ncbi.nlm.nih.gov/pubmed/25099357", "http://www.ncbi.nlm.nih.gov/pubmed/24482116", "http://www.ncbi.nlm.nih.gov/pubmed/26040713", "http://www.ncbi.nlm.nih.gov/pubmed/24641493", "http://www.ncbi.nlm.nih.gov/pubmed/25690770", "http://www.ncbi.nlm.nih.gov/pubmed/24109596" ], "ideal_answer": [ "The endosomal sorting complexes required for transport (ESCRT) are needed for three distinct cellular functions in higher eukaryotes: (i) Multivesicular body formation for the degradation of transmembrane proteins in lysosomes, (ii) midbody abscission during cytokinesis and (iii) retroviral budding." ], "type": "summary", "id": "570a8dcfcf1c325851000027", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells. Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26339479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Endosomal sorting complexes required for transport (ESCRTs) are involved in the formation of multivesicular bodies and sorting of targeted proteins to the yeast vacuole.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25690770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Disassembly of the endosomal sorting complex required for transport (ESCRT) machinery from biological membranes is a critical final step in cellular processes that require the ESCRT function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25637630", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 259, "text": "Evidence has accumulated revealing that efficient autophagic degradation requires functional endosomal sorting complex required for transport (ESCRT) machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25624505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "HIV-1 virions assemble at the plasma membrane of mammalian cells and recruit the endosomal sorting complex required for transport (ESCRT) machinery to enable particle release. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25099357", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 386, "text": "We found that endosomal sorting complex required for transport (ESCRT), involved previously in membrane budding and fission, plays a critical role in plasma membrane repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The ESCRT (endosomal sorting complex required for transport) machinery is known to sort ubiquitinated transmembrane proteins into vesicles that bud into the lumen of multivesicular bodies (MVBs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "The endosomal sorting complexes required for transport (ESCRT) are needed for three distinct cellular functions in higher eukaryotes: (i) Multivesicular body formation for the degradation of transmembrane proteins in lysosomes, (ii) midbody abscission during cytokinesis and (iii) retroviral budding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24641493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24109596", "endSection": "abstract" } ] }, { "body": "Which genes/proteins have been found to inhibit cyclin dependent kinase 4 (CDK4)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7630635", "http://www.ncbi.nlm.nih.gov/pubmed/9031081", "http://www.ncbi.nlm.nih.gov/pubmed/9042862", "http://www.ncbi.nlm.nih.gov/pubmed/10454538", "http://www.ncbi.nlm.nih.gov/pubmed/17881001", "http://www.ncbi.nlm.nih.gov/pubmed/7630199", "http://www.ncbi.nlm.nih.gov/pubmed/9827724", "http://www.ncbi.nlm.nih.gov/pubmed/19147556", "http://www.ncbi.nlm.nih.gov/pubmed/9973200", "http://www.ncbi.nlm.nih.gov/pubmed/9194486", "http://www.ncbi.nlm.nih.gov/pubmed/7652577", "http://www.ncbi.nlm.nih.gov/pubmed/7936665", "http://www.ncbi.nlm.nih.gov/pubmed/9325318", "http://www.ncbi.nlm.nih.gov/pubmed/11790141" ], "ideal_answer": [ "The p15(ink4b) and p16(ink4a) CDK4 inhibitor genes map within the chromosome band 9p21 region deleted frequently in various cancers.The Cdk4 inhibitor p18(Ink4c) is a tumor suppressor. Recent studies of Cyclin D1/Cdk4 have proposed that p21(Waf1/Cip1/Sdi1) plays a key role as a potent Cdk4 inhibitor. p27KIP1 is also a cdk4 ihibitor." ], "exact_answer": [ [ "p16", "p16INK4", "p16INK4a", "MTS1", "CDKN2" ], [ "p15", "p15INK4B" ], [ "p18(Ink4c)" ], [ "p21(Waf1/Cip1/Sdi1)" ], [ "p27KIP1" ] ], "concepts": [ "http://www.uniprot.org/uniprot/CDK4_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050756", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045736", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051358" ], "type": "list", "id": "552435602c8b63434a000009", "snippets": [ { "offsetInBeginSection": 1068, "offsetInEndSection": 1289, "text": "Interestingly, the Cdk inhibitor p18(Ink4c) was induced in the transgenic pineal glands independently of p53, and transgenic mice that lacked Ink4c developed invasive PNET, although at an older age than those lacking p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19147556", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1713, "text": "Our finding that the Cdk4 inhibitor p18(Ink4c) is a tumor suppressor in cyclin D1-driven PNET suggests that pharmacologic interventions to inhibit Cdk4 activity may be a useful chemoprevention or therapeutic strategy in cancer driven by primary RB pathway disruption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19147556", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 704, "text": "Our previous studies showed that while both specific CDK4 inhibitor p16INK4A (P16) and gankyrin bind to cyclin-dependent kinase 4 (CDK4) in similar fashion, only P16 inhibits the kinase activity of CDK4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17881001", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 316, "text": "Recent biological studies of Cyclin D1/Cdk4 have proposed that p21 C-terminal domain (p21(CT)) plays a key role as a potent Cdk4 inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11790141", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1107, "text": "Especially, our data suggests that the D(149)FYHSKRR(156) region of p21 is critical for Cdk4 binding, indicating that the major driving force for complex originates from hydrophobic interaction between p21 and Cdk4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11790141", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 592, "text": "We show that c-Myc prevents induction of the cdk4 inhibitor p15(Ink4b) and the subsequent inhibition of G(1) cdks by TGF-beta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10454538", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 430, "text": "CDK activity is modulated by inhibitors such as p15INK4b and p16INK4a. Loss of function of p15INK4b and p16INK4a (multiple tumor suppressor-I and CDK4 inhibitor) determines impairment in the control of the cell cycle and contributes to the transformation of several cell types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9827724", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 151, "text": "D-type cyclins, in association with the cyclin-dependent kinases CDK4 and CDK6, promote progression through the G1 phase of the cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9827724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "In the present study, we analyzed human ovarian carcinoma cell lines for abnormalities in the tumor suppressor gene Rb (retinoblastoma) and in cyclin-dependent kinase 4 (CDK4) inhibitor genes (p16INK4 and p15INK4B) using molecular biology techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9194486", "endSection": "abstract" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1744, "text": "These data suggest that abnormalities of Rb and CDK4 inhibitor genes (p16INK4, p15INK4B) may be involved in human ovarian carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9194486", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 513, "text": "The mutation, an arginine-to-cysteine exchange at residue 24, was part of the CDK4 peptide recognized by CTLs and prevented binding of the CDK4 inhibitor p16INK4a, but not of p21 or of p27KIP1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7652577", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The p15 and p16 CDK4 inhibitor genes map within the chromosome band 9p21 region deleted frequently in malignant mesothelioma and other cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7630635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "The cyclin-dependent kinase 4 (cdk4) inhibitor (p16INK4/MTS1/CDKN2) gene has been recently identified as a putative tumor suppressor gene because of the high frequency of homozygous deletion observed in numerous human tumor cell lines, including leukemias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7630199", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 369, "text": "The identification of a cdk4 inhibitor, p16INK4, as a target for mutations in cultured tumor lines and primary tumors suggested that RB activity may be affected in these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7936665", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1180, "text": "Roles of cyclin A-Cdk2 as a p27 target and cyclin D2-Cdk4 as a p27 reservoir may result from the differential ability of bound p27 to inhibit the kinase subunit in these complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9325318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Role of the cyclin-dependent kinase 4 and 6 inhibitor gene family p15, p16, p18 and p19 in leukemia and lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9031081", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Identification of functional elements of p18INK4C essential for binding and inhibition of cyclin-dependent kinase (CDK) 4 and CDK6.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973200", "endSection": "title" }, { "offsetInBeginSection": 146, "offsetInEndSection": 364, "text": "One of the INK4 molecules, p16, is also known as multiple tumor suppressor and has been found to be mutated or deleted in various tumors and cell lines. We have previously identified p18 as a member of the INK4 family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Members of the INK4 family of cyclin-dependent kinase (CDK) inhibitors specifically bind and inhibit the G1-specific CDK molecules CDK4 and CDK6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9973200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9042862", "endSection": "title" } ] }, { "body": "What is the role of TRH in hypertension?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11230301", "http://www.ncbi.nlm.nih.gov/pubmed/7554113", "http://www.ncbi.nlm.nih.gov/pubmed/11882596", "http://www.ncbi.nlm.nih.gov/pubmed/3035513", "http://www.ncbi.nlm.nih.gov/pubmed/1595355", "http://www.ncbi.nlm.nih.gov/pubmed/17227965", "http://www.ncbi.nlm.nih.gov/pubmed/11566956", "http://www.ncbi.nlm.nih.gov/pubmed/7498977", "http://www.ncbi.nlm.nih.gov/pubmed/17137217", "http://www.ncbi.nlm.nih.gov/pubmed/8039276", "http://www.ncbi.nlm.nih.gov/pubmed/2854272" ], "ideal_answer": [ "TRH gene overexpression induces hypertension in normal rats and spontaneously hypertensive rats have central TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number. TRH antisense treatment reduces hypertension.\ncentral TRH participates in the hypertension induced by body weight gain probably through its well-known action on sympathetic activity.\nthe pressor effect of intravenous TRH is mediated primarily by a stimulation of alpha-adrenergic receptors. Activation of cardiac beta-adrenoceptors seems to contribute to the blood pressure increasing effect of intravenous TRH. Ang II system is involved in the TRH cardiovascular effects. \nPolymorphisms in TRH (thyrotropin-releasing hormone) are significantly associated with both blood pressure variation and hypertension.\nTRH may mediate the central leptin-induced hypertension effect\nA parallel increase in the density of brain TRH receptors with elevation of blood pressure has been shown and suggests that brain TRH receptors may play an important role in the pathophysiology of hypertension. TRH Receptor gene participates in the etiopathogenesis of essential hypertension." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001795", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001794", "http://www.uniprot.org/uniprot/TRFR_SHEEP", "http://www.uniprot.org/uniprot/TRFR_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008217", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062186", "http://www.disease-ontology.org/api/metadata/DOID:10763", "http://www.uniprot.org/uniprot/TRFR_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006973", "http://www.biosemantics.org/jochem#4254151", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007022", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018025", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013973", "http://www.uniprot.org/uniprot/TRFR_BOVIN" ], "type": "summary", "id": "51602609298dcd4e5100003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "We recently showed that diencephalic TRH may mediate the central leptin-induced pressor effect", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17227965", "endSection": "sections.0" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1167, "text": "that central TRH participates in the hypertension induced by body weight gain probably through its well-known action on sympathetic activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17227965", "endSection": "sections.0" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1360, "text": "Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17137217", "endSection": "sections.0" }, { "offsetInBeginSection": 140, "offsetInEndSection": 422, "text": "We previously reported that thyrotropin-releasing hormone (TRH) precursor gene overexpression induces hypertension in the normal rat and that spontaneously hypertensive rats have central TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11882596", "endSection": "sections.0" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1797, "text": "We propose that because leptin produces central TRH synthesis and release, obesity may induce hypertension through TRH system activation and that the TRH-leptin interaction may thus contribute to the strong association between hypertension and obesity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11882596", "endSection": "sections.0" }, { "offsetInBeginSection": 242, "offsetInEndSection": 369, "text": "We have described that TRH overexpression induces hypertension in a normal rat, which was reversed by TRH antisense treatment. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566956", "endSection": "sections.0" }, { "offsetInBeginSection": 370, "offsetInEndSection": 492, "text": "his treatment also reduces the central TRH hyperactivity in spontaneously hypertensive rats and normalizes blood pressure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566956", "endSection": "sections.0" }, { "offsetInBeginSection": 1643, "offsetInEndSection": 1761, "text": "Our findings support the hypothesis that the TRHR gene participates in the etiopathogenesis of essential hypertension.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11566956", "endSection": "sections.0" }, { "offsetInBeginSection": 98, "offsetInEndSection": 399, "text": "Recently, we described that the TRH precursor gene overexpression induces hypertension in the normal rat. In addition, we published that spontaneously hypertensive rats (SHR) have central extrahypothalamic TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11230301", "endSection": "sections.0" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1540, "text": "the encephalic renin-angiotensin system seems to be crucial in the development and/or maintenance of hypertension in SHR, we investigated the effect of antisense inhibition of TRH on that system and found that TRH antisense treatment significantly diminished the elevated diencephalic angiotensin II (Ang II) content in the SHR without any effect in control animals, suggesting that the Ang II system is involved in the TRH cardiovascular effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11230301", "endSection": "sections.0" }, { "offsetInBeginSection": 1556, "offsetInEndSection": 1678, "text": "he central TRH system seems to be involved in the etiopathogenesis of hypertension in this model of essential hypertension", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11230301", "endSection": "sections.0" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1639, "text": "ong-term treatment with enalapril (5 mg/kg twice daily), which was effective in inhibiting serum angiotensin-converting enzyme activity by more than 50%, decreased arterial blood pressure and preoptic area TRH content of SHR, whereas another vasodilator, diltiazem (10 mg/kg every 8 hours), failed to produce a similar change", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7498977", "endSection": "sections.0" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1469, "text": "the pressor effect of intravenous TRH is mediated primarily by a stimulation of alpha-adrenergic receptors. Adrenal medullectomy appears to enhance the blood pressure response to intravenous TRH. Activation of cardiac beta-adrenoceptors seems to contribute to the blood pressure increasing effect of intravenous TRH in medullectomized animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8039276", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Centrally administered thyrotropin-releasing hormone exerts a well documented hypertensive effect.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1595355", "endSection": "sections.0" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1046, "text": "These results provide evidence for a role of endogenous brain thyrotropin-releasing hormone in the maintenance of hypertension in spontaneously hypertensive rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1595355", "endSection": "sections.0" }, { "offsetInBeginSection": 57, "offsetInEndSection": 209, "text": "in spontaneously hypertensive (SHR) rats the development of hypertension paralleled increases in brain receptors for thyrotropin-releasing hormone (TRH)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2854272", "endSection": "sections.0" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1355, "text": "The results suggest that in addition to the brain, TRH receptors in the spinal cord of SHR rats are also up-regulated and may also play an important role in the regulation of blood pressure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2854272", "endSection": "sections.0" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1781, "text": "The results provide, for the first time, evidence for a parallel increase in the density of brain TRH receptors with elevation of blood pressure, and suggest that brain TRH receptors may play an important role in the pathophysiology of hypertension.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3035513", "endSection": "sections.0" } ] }, { "body": "Is triadin involved in cardiac function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18206802", "http://www.ncbi.nlm.nih.gov/pubmed/17890426", "http://www.ncbi.nlm.nih.gov/pubmed/15191886", "http://www.ncbi.nlm.nih.gov/pubmed/15023559" ], "triples": [ { "p": "http://purl.uniprot.org/core/isolatedFrom", "s": "http://purl.uniprot.org/uniprot/Q28820", "o": "http://purl.uniprot.org/tissues/440" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/440", "o": "Cardiac muscle" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q28820", "o": "http://linkedlifedata.com/resource/#_51323838323000B" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51323838323000B", "o": "Triadin" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/440", "o": "Heart muscle" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInAnatomicalSystem", "s": "http://purl.uniprot.org/uniprot/P82179", "o": "http://purl.uniprot.org/tissues/445" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P82179", "o": "http://linkedlifedata.com/resource/#_503832313739006" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503832313739006", "o": "Triadin" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/445", "o": "Cardiac" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/445", "o": "Cardiac tissue" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/445", "o": "Heart" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/P82179", "o": "http://linkedlifedata.com/resource/#_503832313739009" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_503832313739009", "o": "TRDN" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q13061", "o": "http://linkedlifedata.com/resource/#_51313330363100E" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q13061", "o": "http://linkedlifedata.com/resource/#_51313330363100B" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51313330363100E", "o": "TRDN" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51313330363100B", "o": "Triadin" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q28820", "o": "http://linkedlifedata.com/resource/#_51323838323000E" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51323838323000E", "o": "TRDN" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInAnatomicalSystem", "s": "http://purl.uniprot.org/uniprot/Q28820", "o": "http://purl.uniprot.org/tissues/440" }, { "p": "http://purl.uniprot.org/core/isolatedFrom", "s": "http://purl.uniprot.org/uniprot/P82179", "o": "http://purl.uniprot.org/tissues/445" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q13061", "o": "http://purl.uniprot.org/go/0006936" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0006936", "o": "http://www.geneontology.org/go#GO:0006936" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0006936", "o": "muscle contraction" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/P82179", "o": "http://purl.uniprot.org/keywords/703" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/703", "o": "Sarcoplasmic reticulum" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q13061", "o": "http://purl.uniprot.org/keywords/703" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q28820", "o": "http://purl.uniprot.org/keywords/703" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q13061", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0006936" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0006936", "o": "muscle contraction" }, { "p": "http://purl.uniprot.org/core/isolatedFrom", "s": "http://purl.uniprot.org/uniprot/P82179", "o": "http://purl.uniprot.org/tissues/933" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/933", "o": "Skeletal muscle" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/933", "o": "Striated muscle" }, { "p": "http://purl.uniprot.org/core/isolatedFrom", "s": "http://purl.uniprot.org/uniprot/Q13061", "o": "http://purl.uniprot.org/tissues/933" }, { "p": "http://purl.uniprot.org/core/isolatedFrom", "s": "http://purl.uniprot.org/uniprot/Q28820", "o": "http://purl.uniprot.org/tissues/933" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInAnatomicalSystem", "s": "http://purl.uniprot.org/uniprot/P82179", "o": "http://purl.uniprot.org/tissues/933" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInAnatomicalSystem", "s": "http://purl.uniprot.org/uniprot/Q13061", "o": "http://purl.uniprot.org/tissues/933" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInAnatomicalSystem", "s": "http://purl.uniprot.org/uniprot/Q28820", "o": "http://purl.uniprot.org/tissues/933" } ], "ideal_answer": [ "Yes, triadin is involved in the regulation of cardiac excitation-contraction coupling." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/TRDN_RABIT", "http://www.uniprot.org/uniprot/TRDN_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060048", "http://www.uniprot.org/uniprot/TRDN_CANFA" ], "type": "yesno", "id": "52b2f09f4003448f55000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle. Within this complex, calsequestrin, triadin, and JCN appear to be critical for normal regulation of ryanodine receptor-mediated calcium (Ca) release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18206802", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 873, "text": "Recent studies have uncovered functional roles of both JCN and triadin in the mouse heart, using transgenic overexpression strategies, which exhibit varying phenotypes including mild SR structural alterations, prolongation of Ca transient decay, impaired relaxation, and cardiac hypertrophy and/or heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18206802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Triadin is involved in the regulation of cardiac excitation-contraction coupling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17890426", "endSection": "abstract" }, { "offsetInBeginSection": 1686, "offsetInEndSection": 1792, "text": "Thus the maintenance of triadin expression is essential for normal SR Ca cycling and contractile function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17890426", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 215, "text": "Ca2+ release from the cardiac junctional sarcoplasmic reticulum (SR) is regulated by a complex of proteins, including the ryanodine receptor (RyR), calsequestrin (CSQ), junctin (JCN), and triadin 1 (TRD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15023559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Impaired sarcoplasmic reticulum (SR) Ca release has been suggested to contribute to the depressed cardiac function in heart failure. The release of Ca from the SR may be regulated by the ryanodine receptor, triadin, junctin, calsequestrin, and a histidine-rich, Ca-binding protein (HRC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15191886", "endSection": "abstract" } ] }, { "body": "Which disorders are associated to mutated Hepcidin (HAMP)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21916273", "http://www.ncbi.nlm.nih.gov/pubmed/20837779", "http://www.ncbi.nlm.nih.gov/pubmed/23577916", "http://www.ncbi.nlm.nih.gov/pubmed/19214511", "http://www.ncbi.nlm.nih.gov/pubmed/21862411", "http://www.ncbi.nlm.nih.gov/pubmed/22408404", "http://www.ncbi.nlm.nih.gov/pubmed/24321703", "http://www.ncbi.nlm.nih.gov/pubmed/19342478", "http://www.ncbi.nlm.nih.gov/pubmed/20542038" ], "ideal_answer": [ "Juvenile hemochromatosis (JH) is the most severe form of heriditary hemochromatosis, usually caused by mutations in hemojuvelin (HJV) or hepcidin (HAMP)." ], "exact_answer": [ [ "juvenile hemochromatosis" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/HEPC_ONCMY", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064451" ], "type": "list", "id": "54f21b69c409818c32000007", "snippets": [ { "offsetInBeginSection": 602, "offsetInEndSection": 667, "text": "juvenile hemochromatosis due to hemojuvelin and hepcidin mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321703", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 520, "text": " Mutations in all of the currently known genes implicated in non-HFE HH (hemojuvelin, hepcidin, transferrin receptor 2, and ferroportin) have been reported in patients from the Asia-Pacific region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23577916", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1266, "text": " In conclusion, HAMP and hemojuvelin mutations are rare among Spanish HH patients, and their impact in this population is not significant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214511", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 396, "text": "Juvenile hemochromatosis (JH) is the most severe form, usually caused by mutations in hemojuvelin (HJV) or hepcidin (HAMP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19342478", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1052, "text": "We have identified novel mutations in HJV, HAMP, and SLC40A1 in countries not normally associated with hereditary hemochromatosis (Pakistan, Bangladesh, Sri Lanka, and Thailand).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19342478", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1053, "text": "In humans, loss of TfR2, HJV, and hepcidin itself or FPN mutations result in full-blown hemochromatosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20542038", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 858, "text": "Targeting hepcidin with replacement therapy to decrease iron may be a treatment of not only HCV, HH, and alcoholic cirrhosis, but also PCT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21916273", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 367, "text": "Hepcidin deficiency underlies iron overload in HFE-hemochromatosis as well as in several other genetic iron excess disorders, such as hemojuvelin or hepcidin-related hemochromatosis and transferrin receptor 2-related hemochromatosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862411", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 664, "text": "In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22408404", "endSection": "abstract" } ] }, { "body": "Which protein is the main inhibitor of protein phosphatase 1 (PP1)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16772299", "http://www.ncbi.nlm.nih.gov/pubmed/15345721", "http://www.ncbi.nlm.nih.gov/pubmed/17388107", "http://www.ncbi.nlm.nih.gov/pubmed/18192322", "http://www.ncbi.nlm.nih.gov/pubmed/9033809", "http://www.ncbi.nlm.nih.gov/pubmed/21447388", "http://www.ncbi.nlm.nih.gov/pubmed/8611507", "http://www.ncbi.nlm.nih.gov/pubmed/16774736", "http://www.ncbi.nlm.nih.gov/pubmed/2540000", "http://www.ncbi.nlm.nih.gov/pubmed/19481088", "http://www.ncbi.nlm.nih.gov/pubmed/10811908" ], "ideal_answer": [ "Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), a major eukaryotic Ser/Thr phosphatase. Nonphosphorylated I-1 is inactive, whereas phosphorylated I-1 is a potent PP1 inhibitor. ", "Protein Phosphatase-1 is restrained by its endogenous inhibitor, protein phosphatase inhibitor-1 (PPI-1). Inhibition of the protein phosphatase 1, by inhibitor-1, significantly increases cardiac contractility and calcium handling. Inhibitor-1 becomes a potent inhibitor of protein phosphatase 1 when phosphorylated by cAMP-dependent protein kinase." ], "exact_answer": [ "protein phosphatase inhibitor 1", "inhibitor 1", "PPI-1", "I1" ], "concepts": [ "http://www.uniprot.org/uniprot/PP1_BRAOL" ], "type": "factoid", "id": "550618f58e1671127b000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 930, "text": "The type 1 protein phosphatase (PP1) is a critical negative regulator of Ca(2+) cycling and contractility in the cardiomyocyte. In particular, it mediates restoration of cardiac function to basal levels, after beta-adrenergic stimulation, by dephosphorylating key phospho-proteins. PP1 is a holoenzyme comprised of its catalytic and auxiliary subunits. These regulatory proteins dictate PP1's subcellular localization, substrate specificity and activity. Amongst them, inhibitor-1 is of particular importance since it has been implicated as an integrator of multiple neurohormonal pathways, which finely regulate PP1 activity, at the level of the sarcoplasmic reticulum (SR). In fact, perturbations in the regulation of PP1 by inhibitor-1 have been implicated in the pathogenesis of heart failure, suggesting that inhibitor-1-based therapeutic interventions may ameliorate cardiac dysfunction and remodeling in the failing heart. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19481088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Aberrant beta-adrenergic signaling and depressed calcium homeostasis, associated with an imbalance of protein kinase A and phosphatase-1 activities, are hallmarks of heart failure. Phosphatase-1 is restrained by its endogenous inhibitor, protein phosphatase inhibitor-1 (PPI-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18192322", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 333, "text": "Using this technology, we showed that inhibition of the protein phosphatase 1, by its constitutively active inhibitor-1, significantly increases cardiac contractility and calcium handling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17388107", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1151, "text": "Thus, long-term cardiac specific overexpression of the protein phosphatase 1 inhibitor-1 and the associated increases in cardiac contractility appear to herald changes in a rather small number of proteins, which may reflect important compensatory adaptations in a hyperdynamic heart [corrected]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17388107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Inhibitor-1 becomes a potent inhibitor of protein phosphatase 1 when phosphorylated by cAMP-dependent protein kinase at Thr(35). Moreover, Ser(67) of inhibitor-1 serves as a substrate for cyclin-dependent kinase 5 in the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16772299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), a major eukaryotic Ser/Thr phosphatase. Nonphosphorylated I-1 is inactive, whereas phosphorylated I-1 is a potent PP1 inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10811908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Ser67-phosphorylated inhibitor 1 is a potent protein phosphatase 1 inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10811908", "endSection": "title" }, { "offsetInBeginSection": 339, "offsetInEndSection": 473, "text": "PP1 activity was inhibited by protamine, heparin, okadaic acid (IC50 50 nM) and mammalian inhibitor-1 (IC50 2 nM). On the other hand. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9033809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 463, "text": "The cDNA encoding human brain protein phosphatase inhibitor-1 (I-1) was expressed in Escherichia coli. Following PKA phosphorylation at a threonine, recombinant human I-1 was indistinguishable from rabbit skeletal muscle I-1 as a potent and specific inhibitor of the type-1 protein serine/threonine phosphatase (PP1). N-Terminal phosphopeptides of I-1 that retained the selectivity of intact human I-1 highlighted a functional domain that mediates PP1 inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8611507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "Protein phosphatase inhibitor-1 was purified from bovine adipose tissue. The protein had an apparent molecular mass of 32 kDa by SDS/PAGE and a Stokes' radius of 3.4 nm. It was phosphorylated by cAMP-dependent protein kinase on a threonyl residue; this phosphorylation was necessary for inhibition of protein phosphatase-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2540000", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 559, "text": "Bovine adipose tissue inhibitor-1 was compared directly with rabbit skeletal muscle inhibitor-1 and with a 32000-Mr, dopamine- and cAMP-regulated phosphoprotein from bovine brain (DARPP-32), also an inhibitor of protein phosphatase-1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2540000", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 643, "text": "Protein inhibitor-1 (I-1) specifically inhibits protein phosphatase 1 (PP1), the predominant PLB phosphatase in heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21447388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), the predominating Ser/Thr phosphatase in the heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16774736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Inhibitor-1 (I-1) is a selective inhibitor of protein phosphatase-1 (PP1) and regulates several PP1-dependent signaling pathways, including cardiac contractility and regulation of learning and memory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15345721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), a major eukaryotic Ser/Thr phosphatase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10811908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), the predominating Ser/Thr phosphatase in the heart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16774736", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 642, "text": "Protein inhibitor-1 (I-1) specifically inhibits protein phosphatase 1 (PP1), the predominant PLB phosphatase in heart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21447388", "endSection": "abstract" } ] }, { "body": "What is the role of NETs in systemic lupus erythematosus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24570026", "http://www.ncbi.nlm.nih.gov/pubmed/23945056", "http://www.ncbi.nlm.nih.gov/pubmed/23248629", "http://www.ncbi.nlm.nih.gov/pubmed/21613614", "http://www.ncbi.nlm.nih.gov/pubmed/24205237", "http://www.ncbi.nlm.nih.gov/pubmed/22345666", "http://www.ncbi.nlm.nih.gov/pubmed/22617827", "http://www.ncbi.nlm.nih.gov/pubmed/21389264", "http://www.ncbi.nlm.nih.gov/pubmed/24497360", "http://www.ncbi.nlm.nih.gov/pubmed/24838349", "http://www.ncbi.nlm.nih.gov/pubmed/23224024", "http://www.ncbi.nlm.nih.gov/pubmed/23267025", "http://www.ncbi.nlm.nih.gov/pubmed/24758196", "http://www.ncbi.nlm.nih.gov/pubmed/24295292", "http://www.ncbi.nlm.nih.gov/pubmed/25500436", "http://www.ncbi.nlm.nih.gov/pubmed/20439745" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0081309", "o": "D008180" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12999583", "o": "D008180" } ], "ideal_answer": [ "Neutrophil extracellular traps (NETs) are released via a novel form of cell death called NETosis. NETs, consisting of a chromatin meshwork decorated with antimicrobial peptides, play an important role in the innate response to microbial infections. Clearance of NETs is impaired in a subset of patients with systemic lupus erythematosus, and NETosis is increased in these patients low-density granulocytes, a phenotype that correlates with disease activity. NETs are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. NETs can directly damage tissues - including the endothelium - with implications for lupus nephritis and accelerated atherosclerosis." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:9074", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008180" ], "type": "summary", "id": "56ccccf55795f9a73e000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 498, "text": "Neutrophil extracellular traps (NETs) represent an important defense mechanism against microorganisms. Clearance of NETs is impaired in a subset of patients with systemic lupus erythematosus, and NETosis is increased in neutrophils and, particularly, in low-density granulocytes derived from lupus patients. NETs are toxic to the endothelium, expose immunostimulatory molecules, activate plasmacytoid dendritic cells, and may participate in organ damage through incompletely characterized pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23267025", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 755, "text": "Neutrophil extracellular traps (NETs) are released via a novel form of cell death called NETosis. NETs, consisting of a chromatin meshwork decorated with antimicrobial peptides, play an important role in the innate response to microbial infections. Some lupus patients do not clear NETs normally, a phenotype that correlates with disease activity. Further, lupus neutrophils - and, in particular, an aberrant subset called low-density granulocytes - have an increased propensity to undergo NETosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22617827", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1172, "text": " NETs can also directly damage tissues - including the endothelium - with implications for lupus nephritis and accelerated atherosclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22617827", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 264, "text": "Antimicrobial neutrophil extracellular traps (NETs) are composed of secreted chromatin that may act as a source of autoantigens typical for SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of systemic Lupus erythematosus (SLE), since netting neutrophils release potentially immunogenic autoantigens including histones, LL37, human neutrophil peptide (HNP), and self-DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24205237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Elevated Plasma cfDNA May be Associated with Active Lupus Nephritis and Partially Attributed to Abnormal Regulation of Neutrophil Extracellular Traps (NETs) in Patients with Systemic Lupus Erythematosus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25500436", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "A decreased ability to degrade neutrophil extracellular traps (NETs) is seen in a subgroup of patients with systemic lupus erythematosus (SLE) and correlates with the presence of autoantibodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295292", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 571, "text": "Recent studies have demonstrated that dysregulation of NETs could be involved in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23224024", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 622, "text": "Both exuberant NETosis and impaired clearance of NETs have been implicated in the organ damage of autoimmune diseases, such as systemic lupus erythematosus (SLE), small vessel vasculitis (SVV), and psoriasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21613614", "endSection": "title" }, { "offsetInBeginSection": 297, "offsetInEndSection": 781, "text": "Neutrophil extracellular trap (NET) formation is increased in SLE and has been proposed to contribute to endothelial damage, but the mechanism remains unclear.OBJECTIVE: To determine the mechanism by which enhanced NET formation by low-density granulocytes (LDGs) in SLE contributes to endothelial damage and disrupts the endothelium.RESULTS: The putative role of NET-externalised matrix metalloproteinases (MMPs) in altering the functional integrity of the endothelium was examined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24570026", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 398, "text": "In this study, we investigated how complement interacts with NETs and how NET degradation is affected by complement in SLE patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22345666", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1131, "text": "NETs are a potent stimulus for IFN\u03b1 release by plasmacytoid dendritic cells, and, as such, may play an important role in propagation of the lupus phenotype. NETs can also directly damage tissues - including the endothelium - with implications for lupus nephritis and accelerated atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22617827", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1902, "text": "Active NOS, NOX, and MPO within NETs significantly modify HDL, rendering the lipoprotein proatherogenic. Since NET formation is enhanced in SLE, these findings support a novel role for NET-derived lipoprotein oxidation in SLE-associated CVD and identify additional proatherogenic roles of neutrophils and putative protective roles of antimalarials in autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24838349", "endSection": "abstract" } ] }, { "body": "Which protein is required for Argonaute 2 recruitment to stress granules and P-bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21439943", "http://www.ncbi.nlm.nih.gov/pubmed/19458189" ], "ideal_answer": [ "Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies." ], "exact_answer": [ "Hsp90" ], "type": "factoid", "id": "56cdf5195795f9a73e000045", "snippets": [ { "offsetInBeginSection": 392, "offsetInEndSection": 755, "text": "we examined whether another Hsp90 inhibitor radicicol (RA) affected P-bodies and stress granules. Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies. Although stress granules still assembled in RA-treated cells upon heat shock, they were smaller and more dispersed in the cytoplasm than those in untreated cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458189", "endSection": "title" }, { "offsetInBeginSection": 154, "offsetInEndSection": 515, "text": "Processing bodies (PBs) and stress granules (SGs) are the two main types of ribonucleoprotein complexes with which Argonautes are associated. Targeting of Argonautes to these structures seems to be regulated by different factors. In the present study, we show that heat-shock protein (Hsp) 90 activity is required for efficient targeting of hAgo2 to PBs and SGs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458189", "endSection": "title" }, { "offsetInBeginSection": 590, "offsetInEndSection": 693, "text": "Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439943", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 594, "text": "Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439943", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 517, "text": "In the present study, we show that heat-shock protein (Hsp) 90 activity is required for efficient targeting of hAgo2 to PBs and SGs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458189", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 594, "text": "To verify these observations, we examined whether another Hsp90 inhibitor radicicol (RA) affected P-bodies and stress granules. Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439943", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 594, "text": "Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439943", "endSection": "abstract" } ] }, { "body": "Is Mammaprint approved by the United States Food and Drug Administration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19506735", "http://www.ncbi.nlm.nih.gov/pubmed/18515733", "http://www.ncbi.nlm.nih.gov/pubmed/18786252", "http://www.ncbi.nlm.nih.gov/pubmed/19546609", "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "http://www.ncbi.nlm.nih.gov/pubmed/19879448", "http://www.ncbi.nlm.nih.gov/pubmed/17462970" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2827401", "o": "http://linkedlifedata.com/resource/umls/label/A17680439" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4434464B59390011", "o": "fda" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_51395844503300D", "o": "fda" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4F383737393600D", "o": "fda" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_4530503539300011", "o": "fda" } ], "ideal_answer": [ "Yes, Mammaprint has been approved by the US Food and Drug Administration." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017322", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017327", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017326" ], "type": "yesno", "id": "51487821d24251bc0500002f", "snippets": [ { "offsetInBeginSection": 1432, "offsetInEndSection": 1485, "text": "an FDA-cleared 70-gene signature of MammaPrint panel ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "endSection": "sections.0" }, { "offsetInBeginSection": 460, "offsetInEndSection": 562, "text": "on MammaPrint, the first and only assay for breast cancer management that has been cleared by the FDA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19879448", "endSection": "sections.0" }, { "offsetInBeginSection": 1614, "offsetInEndSection": 1862, "text": "The MammaPrint assay has the advantages of a 510(k) clearance by the US Food and Drug Administration, a larger gene number which may enhance further utility, and the potentially wider patient eligibility including lymph node-positive, ER-negative, ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19546609", "endSection": "sections.0" }, { "offsetInBeginSection": 1391, "offsetInEndSection": 1785, "text": "The MammaPrint assay has the advantages of a 510(k) clearance by the U.S. Food and Drug Administration, a larger gene number, which may enhance further utility, and a potentially wider patient eligibility, including lymph node-positive, estrogen receptor (ER)-negative, and younger patients being accrued into the prospective trial (Microarray in Node-Negative Disease May Avoid Chemotherapy). ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18515733", "endSection": "sections.0" } ] }, { "body": "What is known as Von Hippel\u2013Lindau disease or syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24138046", "http://www.ncbi.nlm.nih.gov/pubmed/22265326", "http://www.ncbi.nlm.nih.gov/pubmed/22659535", "http://www.ncbi.nlm.nih.gov/pubmed/23384228", "http://www.ncbi.nlm.nih.gov/pubmed/23968328", "http://www.ncbi.nlm.nih.gov/pubmed/24292403", "http://www.ncbi.nlm.nih.gov/pubmed/18434768", "http://www.ncbi.nlm.nih.gov/pubmed/21362373", "http://www.ncbi.nlm.nih.gov/pubmed/20375333", "http://www.ncbi.nlm.nih.gov/pubmed/23843833", "http://www.ncbi.nlm.nih.gov/pubmed/18408496", "http://www.ncbi.nlm.nih.gov/pubmed/20231120", "http://www.ncbi.nlm.nih.gov/pubmed/20687511", "http://www.ncbi.nlm.nih.gov/pubmed/11331612", "http://www.ncbi.nlm.nih.gov/pubmed/21955200", "http://www.ncbi.nlm.nih.gov/pubmed/21204227", "http://www.ncbi.nlm.nih.gov/pubmed/20833332", "http://www.ncbi.nlm.nih.gov/pubmed/20442526", "http://www.ncbi.nlm.nih.gov/pubmed/18751708", "http://www.ncbi.nlm.nih.gov/pubmed/22461457", "http://www.ncbi.nlm.nih.gov/pubmed/18203931", "http://www.ncbi.nlm.nih.gov/pubmed/24900047", "http://www.ncbi.nlm.nih.gov/pubmed/23652669" ], "ideal_answer": [ "von Hippel-Lindau (VHL) disease is a rare, autosomal dominantly inherited multisystem disorder characterized by development of a variety of benign and malignant tumors, which are usually accompanied with cysts. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas. The most common causes of death in VHL disease patients are renal cell carcinoma and neurologic complications from cerebellar hemangioblastomas. von Hippel-Lindau (VHL) syndrome is associated with mutations of the VHL tumor suppressor gene (3p25-26). Its estimated incidence ranges from 1 in 36,000 to 1 in 53,000 with a penetrance of up to 95% by age 60. The VHL tumour suppressor gene, responsible for the disease, encodes for a major regulator of the hypoxic response by targeting the transcription factor hypoxia inducible factor (HIF) for degradation. Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes.In addition, many HIFalpha-independent functions of pVHL have recently been identified. These include microtubule-based processes, extracellular matrix assembly and suppression of kidney cyst formation.", "VHL is the result of a germline mutation in the VHL tumor suppressor gene. Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes. These include microtubule-based processes, extracellular matrix assembly and suppression of kidney cyst formation. Clinical symptoms occur first after an age of approximately 30\u00a0years. Main manifestations include central nervous system (CNS) and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeochromocytomas and pancreatic neuroendocrine tumors. Type 1 VHL is predominantly associated with large deletion or truncation mutations which result in an encoded protein with very little or no activity. It is further classified into three other subtypes (2A, 2B, 2C) based on the presence of hemangioblastoma and renal cell carcinoma. In addition, many HIFalpha-independent functions of pVHL have recently been identified. It is associated with retinal and CNS hemangioblastoma and renal cell carcinoma but not pheochromocytoma. Incidence of VHLS is roughly 1 in 36,000 live births and has over 90% penetrance by the age of 65. " ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051794", "http://www.uniprot.org/uniprot/VHLL_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.disease-ontology.org/api/metadata/DOID:14175", "http://www.uniprot.org/uniprot/VHL_MOUSE" ], "type": "summary", "id": "552446612c8b63434a00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 443, "text": "Von Hippel-Lindau syndrome is an autosomal dominant inherited phacomatosis with a predisposition for the central nervous system and retina. There is variable expression with hemangioblastomas in the brain, medulla oblongata, spinal chord, renal carcinoma, pheochromocytoma, pancreatic cysts and islet cell tumors as well as tumors of the endolymphatic sac of the inner ear. Clinical symptoms occur first after an age of approximately 30\u00a0years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292403", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 195, "text": "Von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited systemic cancer syndrome that gives rise to cystic and highly vascularized tumors in many organs, including the eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24138046", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 410, "text": "Von Hippel-Lindau (VHL) disease is a hereditary, autosomal dominant syndrome which is manifested by a range of different benign and malignant tumors. This disease can present with different clinical presentations such as; retinal angioma (RA), hemangioblastoma (HB) of the central nervous system (CNS), pheochromocytoma (Pheo), and epididymal cystadenoma. Tumors are usually accompanied with cysts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1115, "text": "von Hippel-Lindau (VHL) disease is an autosomal-dominant familial cancer syndrome associated with mutations of the VHL tumor suppressor gene (3p25-26). Its estimated incidence ranges from 1 in 36,000 to 1 in 53,000 with a penetrance of up to 95% by age 60. Genotype-phenotype correlation divides VHL into two broad clinical subtypes. Type 1 VHL is predominantly associated with large deletion or truncation mutations which result in an encoded protein with very little or no activity. It is associated with retinal and CNS hemangioblastoma and renal cell carcinoma but not pheochromocytoma. Type 2 is usually associated with missense mutations encoding a protein with limited activity and includes pheochromocytoma. It is further classified into three other subtypes (2A, 2B, 2C) based on the presence of hemangioblastoma and renal cell carcinoma. Visceral cysts in the kidney, pancreas and epididymis, nonfunctioning pancreatic neuroendocrine tumors which often show distinctive clear cell cytology, endolymphatic sac tumors and head and neck paragangliomas are well recognized but less common presenting features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "von Hippel-Lindau (VHL) disease is an inheritable multisystem tumor syndrome characterized by multiple benign and malignant tumors affecting multiple organs. VHL is the result of a germline mutation in the VHL tumor suppressor gene. Molecular genomic analysis routinely confirms the clinical diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23384228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 436, "text": "Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome (1/36,000 live births) with highly penetrance that predispose to the development of a panel of highly vascularized tumors (model of tumoral angiogenesis). Main manifestations include central nervous system (CNS) and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeochromocytomas and pancreatic neuroendocrine tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659535", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 221, "text": "Von Hippel-Lindau (VHL) disease is an inherited syndrome caused by germline mutations in the VHL tumor suppressor gene, predisposing to a variety of neoplasms including pancreatic neuroendocrine tumors (PanNET). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22461457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Von Hippel-Lindau disease is an autosomal dominant disorder involving the development of specific tumours in multiple organs, both benign and malignant. In the CNS, the syndrome is characterized by haemangioblastomas of the retina, spinal cord and brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22265326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Patients with von Hippel-Lindau disease (VHL) often harbor significant disease burden within the CNS, specifically craniospinal-axis hemangioblastomas and endolymphatic sac tumors (ELSTs). The majority (60-80%) of patients with VHL harbor hemangioblastomas, and 10-15% will develop ELSTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21955200", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 171, "text": "Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21362373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 405, "text": "von Hippel-Lindau disease (VHL) disease increases susceptibility to several malignancies, including renal cell carcinoma, haemangioblastomas of the central nervous system or retina and phaeochromocytomas. The VHL tumour suppressor gene, responsible for the disease, encodes for a major regulator of the hypoxic response by targeting the transcription factor hypoxia inducible factor (HIF) for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20833332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Von Hippel-Lindau syndrome (VHLS) is an autosomal dominant familial cancer syndrome arising from germ-line inactivation of the VHL gene on the short arm of chromosome 3. VHLS manifests in a myriad of hyper-vascular tumors of both benign and malignant nature. Incidence of VHLS is roughly 1 in 36,000 live births and has over 90% penetrance by the age of 65. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20687511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 490, "text": "Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is responsible for the development of renal carcinomas, pheochromocytomas and tumours in other organs. The gene product (pVHL) is a central component in the oxygen-sensing pathway through its role in the regulation of the hypoxia-inducible factor (HIF). Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20231120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "Germ line inactivation of the von-Hippel-Lindau (VHL) tumor suppressor gene causes von Hippel-Lindau hereditary cancer syndrome, and somatic mutations of this gene have been linked to the development of sporadic hemangioblastomas and clear cell renal carcinomas. The protein encoded by VHL, pVHL, has no known enzymatic activities but interacts with various partner proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18751708", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 873, "text": "pVHL acts as a multi-purpose adaptor protein that controls different gene expression programs. Through its oxygen-dependent regulation of hypoxia-inducible factor alpha (HIFalpha), pVHL plays a central role in the oxygen-sensing pathway. In addition, many HIFalpha-independent functions of pVHL have recently been identified. These include microtubule-based processes, extracellular matrix assembly and suppression of kidney cyst formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18751708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "von Hippel-Lindau (VHL) disease is an inherited multisystem familial cancer syndrome caused by mutations of the VHL gene on chromosome 3p25. A wide variety of neoplastic processes are known to be associated with VHL disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 572, "text": "von Hippel-Lindau (VHL) disease is a rare, autosomal dominantly inherited multisystem disorder characterized by development of a variety of benign and malignant tumors. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas. The most common causes of death in VHL disease patients are renal cell carcinoma and neurologic complications from cerebellar hemangioblastomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18203931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Von Hippel-Lindau disease (VHL disease) is a hereditary cancer predisposition syndrome caused by mutations of the von Hippel-Lindau tumor suppressor gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23968328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "von Hippel-Lindau disease is an inherited, multisystemic cancer syndrome often involving the retina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18408496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "von Hippel-Lindau (VHL) disease is an autosomal-dominant familial cancer syndrome associated with mutations of the VHL tumor suppressor gene (3p25-26).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23652669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome (1/36,000 live births) with highly penetrance that predispose to the development of a panel of highly vascularized tumors (model of tumoral angiogenesis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22659535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Von Hippel-Lindau (VHL) disease type 2A is an inherited tumor syndrome characterized by predisposition to pheochromocytoma (pheo), retinal hemangioma (RA), and central nervous system hemangioblastoma (HB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21204227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germ line mutation of the von Hippel-Lindau tumor suppressor gene (VHL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11331612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "von Hippel-Lindau (VHL) disease is an inherited multisystem familial cancer syndrome caused by mutations of the VHL gene on chromosome 3p25.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "von Hippel-Lindau (VHL) disease is an inherited multisystem familial cancer syndrome caused by mutations of the VHL gene on chromosome 3p25", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "von Hippel-Lindau disease is an inherited, multisystemic cancer syndrome often involving the retina", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18408496", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 249, "text": "Von Hippel-Lindau disease is an inherited syndrome of multiorgan neoplasia caused by a germline mutation in the von Hippel-Lindau gene and can include central nervous system tumors, renal cell carcinomas and benign pancreatic cystic tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442526", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 133, "text": "von Hippel-Lindau (VHL) disease is a dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20375333", "endSection": "abstract" } ] }, { "body": "Is HER2 active only when it dimerizes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21908901", "http://www.ncbi.nlm.nih.gov/pubmed/23783223", "http://www.ncbi.nlm.nih.gov/pubmed/21147694", "http://www.ncbi.nlm.nih.gov/pubmed/21630056", "http://www.ncbi.nlm.nih.gov/pubmed/22782294", "http://www.ncbi.nlm.nih.gov/pubmed/23990774", "http://www.ncbi.nlm.nih.gov/pubmed/23988598", "http://www.ncbi.nlm.nih.gov/pubmed/22829865", "http://www.ncbi.nlm.nih.gov/pubmed/21538107", "http://www.ncbi.nlm.nih.gov/pubmed/22983903", "http://www.ncbi.nlm.nih.gov/pubmed/23342251", "http://www.ncbi.nlm.nih.gov/pubmed/19934333", "http://www.ncbi.nlm.nih.gov/pubmed/23474221" ], "ideal_answer": [ "Yes, HER2 activation is driven by the formation of various dimer complexes between members of this receptor family." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055503", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0038134", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0038135", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042803", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0038133", "http://www.disease-ontology.org/api/metadata/DOID:0060079", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018719", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019281", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046983", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018734", "http://www.disease-ontology.org/api/metadata/DOID:0060080" ], "type": "yesno", "id": "5509ec41c2af5d5b70000006", "snippets": [ { "offsetInBeginSection": 211, "offsetInEndSection": 320, "text": "HER activation is driven by the formation of various dimer complexes between members of this receptor family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990774", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 516, "text": "rtuzumab is the first humanized monoclonal antibody in a new class of drugs, the HER dimerization inhibitors, approved by the Food and Drug", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23988598", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 699, "text": "Pertuzumab is a novel anti-HER2 monoclonal antibody, which blocks HER2 dimerization with other ligand-activated HER family members. Here, we explored the complement-mediated anti-tumor effects of trastuzumab and pertuzumab on HER2-positive tumor cells of various histological origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474221", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 917, "text": "ays. In this study, we report that an anti-HER2 monoclonal antibody (HER2Mab), which blocks HER2 dimerization with HER3, induces HER3 dimerization with EGFR in both low and high HER2 expressing cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23342251", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 402, "text": "Recent evidence from both basic and clinical studies suggests that ERBB3 (HER3) serves as a key activator of downstream signaling through dimerization with other ERBB proteins and plays a critical role in the widespread clinical resistance to EGFR and HER2 targeting cancer therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23342251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and activation of downstream signaling pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22983903", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Dimerization among the EGFR family of tyrosine kinase receptors leads to allosteric activation of the kinase domains of the partners.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22983903", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1338, "text": "Our results show that quantification of HER dimerization provides information about receptor activation that cannot be obtained by quantification of single receptors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22829865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. It was recently approved by the US FDA for use in combination with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22782294", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 398, "text": "he HER dimerization status may be more important than HER receptor expression per se in determining sensitivity or resistance to a given therapeutic agen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21908901", "endSection": "abstract" }, { "offsetInBeginSection": 1214, "offsetInEndSection": 1247, "text": " and HER2 dimerization inhibitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21630056", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 319, "text": "One of the mechanisms by which tumor cell proliferation can be inhibited consists in hampering HER2 dimerization by targeting its extracellular domain with specific antibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21538107", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 579, "text": "Pertuzumab, a humanized monoclonal antibody, is the first HER2 dimerization inhibitor. It binds to the dimerization site on the HER2 domain and prevents ligand-driven pairing of HER2 with other HER receptors, thus inhibiting tumor cell growth and survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21147694", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 610, "text": "Pertuzumab, another monoclonal antibody, is a HER2 dimerization inhibitor that binds to a different epitope on HER2 than trastuzumab and inhibits HER2 dimer formation with other HER family members such as HER3 and HER1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19934333", "endSection": "abstract" } ] }, { "body": "Which pharmacogenetic test is available for abacavir?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19514905", "http://www.ncbi.nlm.nih.gov/pubmed/16609367", "http://www.ncbi.nlm.nih.gov/pubmed/20602616", "http://www.ncbi.nlm.nih.gov/pubmed/19351209", "http://www.ncbi.nlm.nih.gov/pubmed/21354501", "http://www.ncbi.nlm.nih.gov/pubmed/15247625", "http://www.ncbi.nlm.nih.gov/pubmed/23204921", "http://www.ncbi.nlm.nih.gov/pubmed/18680696", "http://www.ncbi.nlm.nih.gov/pubmed/18332899", "http://www.ncbi.nlm.nih.gov/pubmed/18784465", "http://www.ncbi.nlm.nih.gov/pubmed/18923406", "http://www.ncbi.nlm.nih.gov/pubmed/19372817", "http://www.ncbi.nlm.nih.gov/pubmed/18680695", "http://www.ncbi.nlm.nih.gov/pubmed/20070406", "http://www.ncbi.nlm.nih.gov/pubmed/21691271", "http://www.ncbi.nlm.nih.gov/pubmed/21521028", "http://www.ncbi.nlm.nih.gov/pubmed/20487194", "http://www.ncbi.nlm.nih.gov/pubmed/19207023", "http://www.ncbi.nlm.nih.gov/pubmed/18444831", "http://www.ncbi.nlm.nih.gov/pubmed/18192781", "http://www.ncbi.nlm.nih.gov/pubmed/18256392", "http://www.ncbi.nlm.nih.gov/pubmed/18673126", "http://www.ncbi.nlm.nih.gov/pubmed/17534855", "http://www.ncbi.nlm.nih.gov/pubmed/21142908" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://data.linkedct.org/resource/intervention/61980", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB01048" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://data.linkedct.org/resource/intervention/755", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB01048" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://data.linkedct.org/resource/intervention/29655", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB01048" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/chebi/id/CHEBI:421707", "o": "{(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0663655", "o": "http://linkedlifedata.com/resource/umls/label/A1350342" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A1350342", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A18243547", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1350341", "o": "abacavir" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11833020", "o": "Abacavir" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12783493", "o": "ABACAVIR" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17883542", "o": "abacavir" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A1350340", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "The pharmacogenetic test recommended prior to abacavir administration is the HLA B*5701 genotyping." ], "exact_answer": [ "HLA B*5701 genotyping" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057069", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820", "http://www.biosemantics.org/jochem#4274473", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010597", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025202" ], "type": "factoid", "id": "51487dead24251bc05000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Pharmacogenomic tests offer a promising strategy to improve the safety and efficacy of drug treatment. Compelling examples, such as HLA-B*5701 testing to identify patients at risk for abacavir-associated hypersensitivity, are already changing clinical care", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21691271", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 336, "text": "International HIV treatment guidelines recommend HLA-B*57:01 typing before abacavir administration, in order to reduce the incidence of abacavir hypersensitivity reactions, the major cause of early therapy discontinuation. A fast, sensitive and specific test for HLA-B*57:01 detection has been developed in the present study.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21521028", "endSection": "sections.0" }, { "offsetInBeginSection": 701, "offsetInEndSection": 872, "text": "The rollout of HLA-B\u22175701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21354501", "endSection": "sections.0" }, { "offsetInBeginSection": 528, "offsetInEndSection": 857, "text": "he aim of the session, using real-world examples (KRAS/panitumumab and HLA-B*5701/abacavir), was to identify good scientific principles that would guide the design of studies to identify subgroups of responders during development programs (including marketed drugs), which could subsequently be used to guide treatment decisions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21142908", "endSection": "sections.0" }, { "offsetInBeginSection": 812, "offsetInEndSection": 965, "text": "HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602616", "endSection": "sections.0" }, { "offsetInBeginSection": 296, "offsetInEndSection": 481, "text": "Successful results that have been achieved within the field of pharmacogenomics so far are, to name a few, HLA-B*5701 screening to avoid hypersensitivity to the antiretroviral abacavir,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20487194", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 234, "text": "Prospective pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 allele can significantly reduce the number of cases of abacavir-related hypersensitivity among HIV-infected patients treated with this drug.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20070406", "endSection": "sections.0" }, { "offsetInBeginSection": 27, "offsetInEndSection": 190, "text": "development of HLA-B*5701 genetic screening as a means of preventing drug hypersensitivity reactions caused by a commonly prescribed antiretroviral drug, abacavir.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19514905", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 615, "text": "Abacavir hypersensitivity syndrome (AHS) is a potentially life-threatening illness occurring in 4-8% of those initiating the drug. Early studies identified a strong association between the MHC class I allele HLA-B*5701 and AHS. These studies suggested that HLA-B*5701 holds promise as a screening test to prevent AHS, but concern arose from HLA-B*5701-negative cases with a clinical diagnosis of AHS, and particularly from early reports of apparently low sensitivities of HLA-B*5701 for AHS in patients of non-White race. However, open screening studies suggested that HLA-B*5701 screening can largely eliminate AHS", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19351209", "endSection": "sections.0" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1167, "text": "Current HIV treatment guidelines have been revised to reflect the recommendation that HLA-B*5701 screening be incorporated into routine care for patients who may require abacavir.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19351209", "endSection": "sections.0" }, { "offsetInBeginSection": 1750, "offsetInEndSection": 1896, "text": "The research approach applied to AHS has led to a genetic screening test being successfully implemented globally in primary HIV clinical practice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19351209", "endSection": "sections.0" }, { "offsetInBeginSection": 434, "offsetInEndSection": 736, "text": "The clinical utility of prospective HLA-B*5701 screening was demonstrated in a blinded randomized clinical trial and in open-label cohorts. Screening has been incorporated into clinical practice and the ABC HSR pharmacogenetics program has been highlighted as a success by pharmacogenetics researchers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19207023", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Abacavir hypersensitivity (ABC HSR) is a treatment-limiting adverse event associated with the use of the antiretroviral medicine, abacavir.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19207023", "endSection": "sections.0" }, { "offsetInBeginSection": 302, "offsetInEndSection": 433, "text": "The major histocompatibility complex allele, HLA-B*5701, was identified retrospectively and confirmed with independent sample sets.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19207023", "endSection": "sections.0" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 1968, "text": "he most significant advance for clinical practice is the correlation between the presence of the HLA-B*5701 allele and hypersensitivity reaction to abacavir. In particular, one clinical trial with a large number of patients from distinct ethnic groups found that the probability of not developing hypersensitivity reaction (immunologically confirmed) was 100% if the patient was HLA-B*5701-negative. These data suggest the need to implement this test in daily clinical practice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18680696", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "The aim of the PREDICT-1 study was to determine the clinical utility of the pharmacogenetic test identifying HLA-B*5701 to reduce the incidence of hypersensitivity reaction to abacavir, diagnosed clinically and with immunological confirmation, as well as to reduce unwarranted withdrawal of this drug", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18680695", "endSection": "sections.0" }, { "offsetInBeginSection": 1949, "offsetInEndSection": 2116, "text": "the identification of HLA-B(*)5701 as a highly sensitive and specific predictive marker for abacavir treated patients who will develop hypersensitivity syndrome (HSS).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18923406", "endSection": "sections.0" }, { "offsetInBeginSection": 2881, "offsetInEndSection": 3144, "text": "Clinical consensus panels rapidly recommended abacavir as the preferred therapy along with HLA-B(*)5701 pre-testing, immediately increasing the market share of abacavir with respect to other reverse transcriptases that are associated with there own adverse events", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18923406", "endSection": "sections.0" }, { "offsetInBeginSection": 1889, "offsetInEndSection": 2041, "text": "Pharmacogenetic testing for HLA-B*5701 is cost-effective only if abacavir-based treatment is as effective and costs less than tenofovir-based treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18784465", "endSection": "sections.0" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1875, "text": "HLA-B*5701 testing remained the preferred strategy only if abacavir-based treatment had equal efficacy and cost less per month than tenofovir-based treatment. Results were also sensitive to the cost of HLA-B*5701 testing and the prevalence of HLA-B*5701.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18784465", "endSection": "sections.0" }, { "offsetInBeginSection": 492, "offsetInEndSection": 685, "text": "The strong association of the abacavir hypersensitivity reaction with HLA-B*5701 permits testing patients for the allele, and if present avoiding the drug and therefore preventing the reaction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18673126", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 243, "text": "Although the human leukocyte antigen (HLA)-B*5701 is highly associated with a hypersensitivity reaction (HSR) to abacavir (ABC), variable sensitivities have been reported when clinical data alone have been used to define an ABC HSR", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18444831", "endSection": "sections.0" }, { "offsetInBeginSection": 1867, "offsetInEndSection": 2132, "text": "Although IC ABC HSRs are uncommon in black persons, the 100% sensitivity of HLA-B*5701 as a marker for IC ABC HSRs in both US white and black patients suggests similar implications of the association between HLA-B*5701 positivity and risk of ABC HSRs in both races.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18444831", "endSection": "sections.0" }, { "offsetInBeginSection": 351, "offsetInEndSection": 535, "text": "A strong statistical association between the major histocompatibility complex allele, HLA-B*5701, and clinically diagnosed ABC HSR was identified but varied between racial populations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18332899", "endSection": "sections.0" }, { "offsetInBeginSection": 650, "offsetInEndSection": 1137, "text": "In a randomized, prospective study evaluating the clinical utility of HLA-B*5701 screening, avoidance of ABC in HLA-B*5701-positive patients significantly reduced clinically diagnosed ABC HSR and eliminated patch test-positive ABC HSR. Finally, a retrospective PGx study supports the generalizability of the association across races. Prospective HLA-B*5701 screening should greatly reduce the incidence of ABC HSR by identifying patients at high risk for ABC HSR before they are treated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18332899", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 115, "text": "Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256392", "endSection": "sections.0" }, { "offsetInBeginSection": 1648, "offsetInEndSection": 2014, "text": "HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256392", "endSection": "sections.0" }, { "offsetInBeginSection": 729, "offsetInEndSection": 950, "text": "For abacavir in particular, the use of HLA-B*5701 as a screening test appears to be generalizable across racially diverse populations and has been supported by both observational, and blinded randomized controlled trials.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18192781", "endSection": "sections.0" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1597, "text": "HLA-B*5701 screening to prevent abacavir hypersensitivity is currently the most relevant to clinical practice and highlights that the promise of cost-effective testing can be facilitated by robust laboratory methodology and quality assurance programs that can be applied to diverse treatment settings.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18192781", "endSection": "sections.0" }, { "offsetInBeginSection": 623, "offsetInEndSection": 773, "text": "the major histocompatibility complex HLA-B*5701 allele has been associated with hypersensitivity to abacavir (ABC) by several independent researchers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17534855", "endSection": "sections.0" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1284, "text": "The strong association between HLA-B5701 and abacavir hypersensitivity reaction shows promise for a genetic screening test to be feasibly incorporated into clinical practice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19372817", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 399, "text": "Abacavir hypersensitivity reaction (ABC HSR) is a potentially life-threatening adverse reaction that affects approximately 8% of patients that initiate this antiretroviral drug. Independent groups have shown a strong predictive association between ABC HSR and HLA-B*5701, indicating that exclusion of HLA-B*5701 positive individuals from abacavir treatment would largely prevent ABC HSR.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16609367", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 253, "text": "Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue reverse transcriptase inhibitor, causes severe hypersensitivity in 4-8% of patients. HLA B*5701 is a known genetic risk factor for abacavir hypersensitivity in Caucasians.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15247625", "endSection": "sections.0" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1788, "text": "Abacavir hypersensitivity is associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this appears to be a cost-effective use of healthcare resources.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15247625", "endSection": "sections.0" } ] }, { "body": "Are microRNA (miR) regulated through DNA methylation of their promoters?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18677110", "http://www.ncbi.nlm.nih.gov/pubmed/19807731", "http://www.ncbi.nlm.nih.gov/pubmed/23229728", "http://www.ncbi.nlm.nih.gov/pubmed/23153241", "http://www.ncbi.nlm.nih.gov/pubmed/24238656", "http://www.ncbi.nlm.nih.gov/pubmed/23707524", "http://www.ncbi.nlm.nih.gov/pubmed/22715154", "http://www.ncbi.nlm.nih.gov/pubmed/22710432", "http://www.ncbi.nlm.nih.gov/pubmed/23658527" ], "ideal_answer": [ "Dysregulation of miRNA expression involved in cancer and Alzheimer's disease can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoter. Epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM).", "Dysregulation of miRNA expression involved in cancer can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoterRecently, epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM)" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012926", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006306", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044030", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247" ], "type": "yesno", "id": "53636e727d100faa0900000d", "snippets": [ { "offsetInBeginSection": 1121, "offsetInEndSection": 1575, "text": "We found that Tcf3 down-regulation in the context of constitutively active Wnt signaling does not result from promoter DNA methylation but is likely to be caused by a plethora of mechanisms at both the RNA and protein level as shown by the observed decrease in activating histone marks (H3K4me3 and H3-acetylation) and the upregulation of miR-211, a novel Wnt-regulated microRNA that targets Tcf3 and attenuates early neural differentiation in mouse ESCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 127, "text": "ene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19807731", "endSection": "title" }, { "offsetInBeginSection": 878, "offsetInEndSection": 1007, "text": "Whereas a CpG island was identified within the promoter element of MIR22, no promoter DNA methylation was detected in these cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19807731", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 139, "text": "xtensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22710432", "endSection": "title" }, { "offsetInBeginSection": 592, "offsetInEndSection": 741, "text": "Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22710432", "endSection": "abstract" }, { "offsetInBeginSection": 1227, "offsetInEndSection": 1461, "text": "Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22710432", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 53, "text": "NA methylation of microRNA genes in multiple myeloma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22715154", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 511, "text": "Recently, epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22715154", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 41, "text": "ethylation of tumor suppressor microRNAs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153241", "endSection": "title" }, { "offsetInBeginSection": 191, "offsetInEndSection": 345, "text": "Dysregulation of miRNA expression involved in cancer can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153241", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 443, "text": "Of note, DNA methylation of tumor suppressor miRNAs has been implicated in various human cancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153241", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 625, "text": "Moreover, miRNA silencing mediated by aberrant promoter DNA methylation can potentially be reversed by hypomethylating agents, and hence may pose a new therapeutic target in cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153241", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 838, "text": " In this review, the authors will focus on the aberrant methylation of miRNAs in the pathogenesis of lymphoid malignancies including chronic lymphocytic leukemia, multiple myeloma and acute lymphoblastic leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153241", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 1026, "text": "Here, we review those miRNAs implicated in AD that are regulated by promoter DNA methylation and/or chromatin modifications and, which frequently direct the expression of constituents of the epigenetic machinery, concluding with the delineation of a complex epigenetic-miRNA regulatory network and its alterations in AD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24238656", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 943, "text": "Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation and the interaction of DNA methylation with miRNAs involved in the regulation of HSC activation and liver fibrosi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707524", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1165, "text": "Instead, the cell type-specific silencing of these genes is due to enhanced p21 mRNA degradation, 14-3-3sigma promoter DNA methylation and reduced processing of the miR-34a primary transcript", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18677110", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 207, "text": "Some tumor-suppressive miRNAs are known to be epigenetically silenced by promoter DNA methylation in cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229728", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 339, "text": "In the present study, we aimed to identify miRNA genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229728", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 806, "text": "It was found that miR-335, which is harbored within an intron of its protein-coding host gene, MEST, was downregulated by aberrant promoter hypermethylation via further methylation assays, including methylation-specific PCR, combined bisulfite and restriction analysis, bisulfite sequencing analysis and 5-aza-2'-deoxycytidine treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229728", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1134, "text": "he levels of miR-335/MEST methylation were significantly higher in 18 (90%) out of 20 primary HCC tumors, compared to their non-tumor tissue counterparts (P<0.001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229728", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1568, "text": "In conclusion, our results indicate that expression of miR-335 is reduced by aberrant DNA methylation in HCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229728", "endSection": "abstract" } ] }, { "body": "Are nucleosomes positioned at DNA replication origins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21148149", "http://www.ncbi.nlm.nih.gov/pubmed/19463783", "http://www.ncbi.nlm.nih.gov/pubmed/1587867", "http://www.ncbi.nlm.nih.gov/pubmed/20351051" ], "ideal_answer": [ "No, origins of replication occur in nucleosome-free regions in both budding yeast and Drosophila. Open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018741", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009707", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051738", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042522", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051716" ], "type": "yesno", "id": "513596225274a5fb0700000d", "snippets": [ { "offsetInBeginSection": 400, "offsetInEndSection": 663, "text": "yeast origins are characterized by an asymmetric pattern of positioned nucleosomes flanking the ACS. The origin sequences are sufficient to maintain a nucleosome-free origin; however, ORC is required for the precise positioning of nucleosomes flanking the origin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20351051", "endSection": "sections.0" }, { "offsetInBeginSection": 258, "offsetInEndSection": 345, "text": "Here, we identify nucleosome occupancy as a likely candidate to set up ORI distribution", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463783", "endSection": "sections.0" }, { "offsetInBeginSection": 442, "offsetInEndSection": 570, "text": "we demonstrate that open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19463783", "endSection": "sections.0" }, { "offsetInBeginSection": 294, "offsetInEndSection": 466, "text": "Nucleosome assembly of the template prevented DNA replication. Replication of chromosomes was severely inhibited at more than two-thirds of physiological nucleosome density", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1587867", "endSection": "sections.0" } ] }, { "body": "Which are the most under-represented oligonucleotides in higher eukaryote genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19536338", "http://www.ncbi.nlm.nih.gov/pubmed/7498525", "http://www.ncbi.nlm.nih.gov/pubmed/12112308", "http://www.ncbi.nlm.nih.gov/pubmed/9725240", "http://www.ncbi.nlm.nih.gov/pubmed/12943801", "http://www.ncbi.nlm.nih.gov/pubmed/7504188", "http://www.ncbi.nlm.nih.gov/pubmed/8893856", "http://www.ncbi.nlm.nih.gov/pubmed/1741388", "http://www.ncbi.nlm.nih.gov/pubmed/16531485", "http://www.ncbi.nlm.nih.gov/pubmed/8543806", "http://www.ncbi.nlm.nih.gov/pubmed/3996596", "http://www.ncbi.nlm.nih.gov/pubmed/11070050" ], "ideal_answer": [ "The oligonucleotides containing the CG and TA dinucleotide are generally under-represented in higher eukaryote genomes", "TpA is the most underepresented dinucleotide followed closely by CpG. For trinucleotides, GCA/TGC tends to be under-represented in phage, human viral, and eukaryotic sequences, and CTA/TAG is strongly under-represented in many prokaryotic, eukaryotic, and viral sequences. For higher lengts alternating Purine/Pyrimidine tracts are underepresented up to 60%.", "Oligonucleotides containing CG and TA dinucleoides" ], "exact_answer": [ [ "TA" ], [ "CG" ], [ "(PuPy)n" ], [ "GCA/TGC" ], [ "CTA/TAG" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056890", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009841" ], "type": "list", "id": "52e203bc98d0239505000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Unusual frequencies of certain alternating purine-pyrimidine runs in natural DNA sequences", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3996596", "endSection": "title" }, { "offsetInBeginSection": 379, "offsetInEndSection": 624, "text": "Octanucleotides are the most deficient, occurring at only 60% of the frequency expected in random sequences. An unexpectedly high proportion of these octamers consists of alternating tetramers with the repeat structure (PuPyPuPy)2 or (PyPuPyPu)2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3996596", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 488, "text": "For dinucleotides, TA is almost universally under-represented, with the exception of vertebrate mitochondrial genomes, and CG is strongly under-represented in vertebrates and in mitochondrial genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1741388", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1104, "text": "For trinucleotides, GCA.TGC tends to be under-represented in phage, human viral, and eukaryotic sequences, and CTA.TAG is strongly under-represented in many prokaryotic, eukaryotic, and viral sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1741388", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 252, "text": "The dinucleotide CpG is significantly under-represented in vertebrate DNA and is usually methylated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8543806", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 394, "text": "One such pattern recognition system is based on unmethylated CpG dinucleotides in particular sequence contexts (CpG motifs); these motifs are common in bacterial DNA but are under-represented (\"CpG suppression\") and methylated in vertebrate DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9725240", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1318, "text": "We argue that the significant under-represented motif pattern of CpG in an AU context--which is found in both the ssRNA viruses and innate genes, and has decreased throughout the history of H1N1 influenza replication in humans--is immunostimulatory and has been selected against during the co-evolution of viruses and host innate immune genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19536338", "endSection": "abstract" } ] }, { "body": "Does nimotuzumab improve survival of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21575527", "http://www.ncbi.nlm.nih.gov/pubmed/19293809", "http://www.ncbi.nlm.nih.gov/pubmed/21483304", "http://www.ncbi.nlm.nih.gov/pubmed/23575267", "http://www.ncbi.nlm.nih.gov/pubmed/24521695", "http://www.ncbi.nlm.nih.gov/pubmed/23754473", "http://www.ncbi.nlm.nih.gov/pubmed/21171927", "http://www.ncbi.nlm.nih.gov/pubmed/23782513", "http://www.ncbi.nlm.nih.gov/pubmed/24571331", "http://www.ncbi.nlm.nih.gov/pubmed/18094616", "http://www.ncbi.nlm.nih.gov/pubmed/23060940" ], "ideal_answer": [ "Yes. Nimotuzumab improves survival of adult and pediatric patients diagnosed with glioblastoma and with other high-grade gliomas." ], "exact_answer": "yes", "type": "yesno", "id": "54d901ec4b1fd0d33c000006", "snippets": [ { "offsetInBeginSection": 1369, "offsetInEndSection": 1454, "text": "The survival times were similar to those seen in historical data of standard therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24571331", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1446, "text": "The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24521695", "endSection": "abstract" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1752, "text": "This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24521695", "endSection": "abstract" }, { "offsetInBeginSection": 1534, "offsetInEndSection": 1827, "text": "The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. CONCLUSIONS: In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23782513", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 813, "text": "Nimotuzumab was well-tolerated and treatment with the antibody yielded a survival benefit: median survival time was 32.66 mo and the 2-y survival rate was 54.2%. This study demonstrated the feasibility of prolonged administration of nimotuzumab and showed preliminary evidence of clinical benefit in HGG patients with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23575267", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 223, "text": " Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21575527", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1872, "text": "CONCLUSIONS: Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21575527", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 322, "text": "It has been evaluated in malignant brain tumors in adults and children, and shown to be therapeutically safe and effective in terms of increased survival and improved quality of life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21483304", "endSection": "abstract" }, { "offsetInBeginSection": 2046, "offsetInEndSection": 2329, "text": "Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21483304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23060940", "endSection": "title" }, { "offsetInBeginSection": 2044, "offsetInEndSection": 2326, "text": "Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21483304", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1750, "text": "This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24521695", "endSection": "abstract" }, { "offsetInBeginSection": 2046, "offsetInEndSection": 2327, "text": "Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21483304", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1060, "text": "A multicenter exploratory study combining nimotuzumab and radiotherapy showed disease control and an overall patient survival similar to previous experiences along with an improvement in the quality of patient survival and no severe side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21171927", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 267, "text": "Combining craniospinal irradiation (CSI) with concurrent temozolomide and nimotuzumab therapy may slightly improve tumor control and overall survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754473", "endSection": "abstract" } ] }, { "body": "List co-morbidities that may occur together with \"Stiff man Syndrome\"", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2135382", "http://www.ncbi.nlm.nih.gov/pubmed/7714921", "http://www.ncbi.nlm.nih.gov/pubmed/12803695", "http://www.ncbi.nlm.nih.gov/pubmed/8464926", "http://www.ncbi.nlm.nih.gov/pubmed/8381208", "http://www.ncbi.nlm.nih.gov/pubmed/16006304", "http://www.ncbi.nlm.nih.gov/pubmed/9443464", "http://www.ncbi.nlm.nih.gov/pubmed/9771977", "http://www.ncbi.nlm.nih.gov/pubmed/8710121", "http://www.ncbi.nlm.nih.gov/pubmed/6859058", "http://www.ncbi.nlm.nih.gov/pubmed/8263140" ], "ideal_answer": [ "SMS (Stiff man Syndrome) is is a rare disorder of the central nervous system of probable autoimmune origin and as such is associated with other autoimmune diseases, such as Insulin Dependent Diabetes Mellitus . GAD-65 is a dominant auto-antigen that is found both in in stiff-man syndrome and insulin-dependent diabetes mellitus. TRAB -positive Graves' disease has been reported to occur together with SMS. \nIn a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.\n\nHCV may be the etiologic virus of progressive encephalomyelitis with rigidity; a rare disorder similar to stiff-man syndrome although different because it is progressive and fatal.\nIt is possible that the reported case of association of progressive dementia with concomitant development of stiff-man syndrome in an elderly man represents an exaggerated form of such motor disturbances in dementia, and that clinical and electromyographic features of stiff-man syndrome may be present with increased incidence in patients with dementia." ], "exact_answer": [ [ "Insulin Dependent Diabetes Mellitus", "type I (insulin-dependent) diabetes mellitus (IDDM)" ], [ "Grave's disease" ], [ "Breast Cancer" ], [ "Dementia" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016750", "http://www.disease-ontology.org/api/metadata/DOID:13366" ], "type": "list", "id": "515df86a298dcd4e5100002e", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 162, "text": "To report an association between two autoimmune conditions, Graves' disease and stiff-person (stiff-man) syndrome, and discuss the relevant literature.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006304", "endSection": "sections.0" }, { "offsetInBeginSection": 1747, "offsetInEndSection": 1919, "text": "This case illustrates the association between TRAB-positive Graves' disease and stiff-person syndrome and the improvement of Graves' disease with immunosuppressive therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006304", "endSection": "sections.0" }, { "offsetInBeginSection": 763, "offsetInEndSection": 943, "text": "HCV may be the etiologic virus of progressive encephalomyelitis with rigidity; a rare disorder similar to stiff-man syndrome although different because it is progressive and fatal.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12803695", "endSection": "sections.0" }, { "offsetInBeginSection": 474, "offsetInEndSection": 624, "text": "The triad of stiff-man syndrome, breast cancer, and autoantibodies against amphiphysin identifies a new autoimmune paraneoplastic syndrome of the CNS.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9443464", "endSection": "sections.0" }, { "offsetInBeginSection": 128, "offsetInEndSection": 230, "text": "GAD has been suggested as an autoantigen in insulin-dependent diabetes mellitus and stiff-man syndrome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7714921", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Stiff-man syndrome (SMS) is a rare disorder of the central nervous system of probable autoimmune origin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8263140", "endSection": "sections.0" }, { "offsetInBeginSection": 105, "offsetInEndSection": 227, "text": "Patients with SMS often have other autoimmune diseases, in particular type I (insulin-dependent) diabetes mellitus (IDDM).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8263140", "endSection": "sections.0" }, { "offsetInBeginSection": 319, "offsetInEndSection": 414, "text": "GAD-65 is a dominant autoantigen in stiff-man syndrome and insulin-dependent diabetes mellitus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8464926", "endSection": "sections.0" }, { "offsetInBeginSection": 269, "offsetInEndSection": 429, "text": "In this group, there is a striking association of the stiff-man syndrome with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8381208", "endSection": "sections.0" }, { "offsetInBeginSection": 439, "offsetInEndSection": 508, "text": "We studied three women with the stiff-man syndrome and breast cancer,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8381208", "endSection": "sections.0" }, { "offsetInBeginSection": 683, "offsetInEndSection": 1030, "text": "RESULTS: Autoantibodies directed against a 128-kd brain protein were found in two of the women with the stiff-man syndrome and breast cancer. These results led to a search for breast cancer in the third patient with the stiff-man syndrome, who also had autoantibodies. A small invasive ductal carcinoma was detected by ultrasonography and removed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8381208", "endSection": "sections.0" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1741, "text": "CONCLUSIONS: In a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8381208", "endSection": "sections.0" }, { "offsetInBeginSection": 93, "offsetInEndSection": 282, "text": "We have previously reported the presence of autoantibodies against glutamic acid decarboxylase (GAD) in a patient with stiff-man syndrome, epilepsy, and insulin-dependent diabetes mellitus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2135382", "endSection": "sections.0" }, { "offsetInBeginSection": 773, "offsetInEndSection": 994, "text": "These findings support the hypothesis that stiff-man syndrome is an autoimmune disease and suggest that GAD is the primary autoantigen involved in stiff-man syndrome and the associated insulin-dependent diabetes mellitus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2135382", "endSection": "sections.0" }, { "offsetInBeginSection": 488, "offsetInEndSection": 766, "text": "An elderly man with progressive dementia and concomitant development of stiff-man syndrome is described. He had not had stiff-man syndrome one year earlier, when he had only mild dementia. An association between stiff-man syndrome and dementia has not been previously described.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6859058", "endSection": "sections.0" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1211, "text": "It is possible that this patient represents an exaggerated form of such motor disturbances in dementia, and that clinical and electromyographic features of stiff-man syndrome may be present with increased incidence in patients with dementia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6859058", "endSection": "sections.0" } ] }, { "body": "Which mechanisms underlie adaptive mutagenesis (stationary-phase mutagenesis) in Bacillus subtilis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9308969", "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "http://www.ncbi.nlm.nih.gov/pubmed/22201950", "http://www.ncbi.nlm.nih.gov/pubmed/22056936", "http://www.ncbi.nlm.nih.gov/pubmed/15375129", "http://www.ncbi.nlm.nih.gov/pubmed/24914186", "http://www.ncbi.nlm.nih.gov/pubmed/12270822", "http://www.ncbi.nlm.nih.gov/pubmed/16950921", "http://www.ncbi.nlm.nih.gov/pubmed/12644484", "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "http://www.ncbi.nlm.nih.gov/pubmed/20971907", "http://www.ncbi.nlm.nih.gov/pubmed/17917870" ], "ideal_answer": [ "Increased transcription levels potentiate adaptive mutagenesis. Central to stationary-phase mutagenesis in B. subtilis is the requirement for Mfd protein (transcription repair coupling factor). The B. subtilis' ability to accumulate chromosomal mutations under conditions of starvation is influenced by cell differentiation and transcriptional derepression, as well as by proteins homologous to transcription and repair factors. Under conditions of nutritional stress, the processing of deaminated bases in B. subtilis may normally occur in an error-prone manner to promote adaptive mutagenesis. A functional RecA protein is not required for adaptive mutagenesis, which seems to be independent of recombination-dependent repair and, in some cases, of the Y DNA polymerases. Oxidative stress-induced DNA damage has been associated with adaptive mutagenesis. The occurrence of such mutations is exacerbated by reactive oxygen species. Starved B. subtilis cells lacking a functional error prevention GO (8-oxo-G) system (composed of YtkD, MutM, and YfhQ) had a dramatic propensity to increase the number of stationary-phase-induced revertants. The MMR (encoded by the mutSL operon) protects B. subtilis from stationary-phase mutations. The MMR modulation of the mutagenic/antimutagenic properties of MutY regulates stationary-phase mutagenesis. Two of the genes that are involved in the regulation of post-exponential phase prokaryotic differentiation, comA and comK, are involved in adaptive mutagenesis. Also, YqjH, a homolog of DinB protein, plays a role in stationary phase mutagenesis." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001412", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060274", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060275" ], "type": "summary", "id": "553f5a20ab98a37113000006", "snippets": [ { "offsetInBeginSection": 1508, "offsetInEndSection": 1674, "text": "under conditions of nutritional stress, the processing of deaminated bases in B. subtilis may normally occur in an error-prone manner to promote adaptive mutagenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056936", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1595, "text": "the B. subtilis' ability to accumulate chromosomal mutations under conditions of starvation is influenced by cell differentiation and transcriptional derepression, as well as by proteins homologous to transcription and repair factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17917870", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 775, "text": "the loss of Mfd has a depressive effect on stationary-phase mutagenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16950921", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1152, "text": "In Bacillus subtilis, transcription-associated mutagenesis has been shown to be independent of recombination-dependent repair and, in some cases, of the Y DNA polymerases. Central to stationary-phase mutagenesis in B. subtilis is the requirement for Mfd, transcription coupling repair factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22201950", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 360, "text": "Oxidative stress-induced DNA damage has been associated with generation of adaptive His(+) and Met(+) but not Leu(+) revertants in strain Bacillus subtilis YB955", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20971907", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 542, "text": "an interplay between MutY and MutSL (mismatch repair system [MMR]) plays a pivotal role in the production of adaptive Leu(+) revertants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20971907", "endSection": "abstract" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1465, "text": "MMR regulation of the mutagenic/antimutagenic properties of MutY promotes stationary-phase mutagenesis in B. subtilis cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20971907", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 976, "text": "To further examine the correlation between transcription and adaptive mutation, we placed a point-mutated allele, leuC427, under the control of an inducible promoter and assayed the level of reversion to leucine prototrophy under conditions of leucine starvation. Our results demonstrate that the level of Leu(+) reversions increased significantly in parallel with the induced increase in transcription levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 181, "text": "a Bacillus subtilis strain deficient in mismatch repair (MMR; encoded by the mutSL operon) promoted the production of stationary-phase-induced mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 698, "text": "starved B. subtilis cells lacking a functional error prevention GO (8-oxo-G) system (composed of YtkD, MutM, and YfhQ) had a dramatic propensity to increase the number of stationary-phase-induced revertants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 870, "text": "the occurrence of mutations is exacerbated by reactive oxygen species in nondividing cells of B. subtilis having an inactive GO system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1324, "text": "the absence or depression of both the MMR and GO systems contributes to the production of stationary-phase mutants in B. subtilis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "abstract" }, { "offsetInBeginSection": 1374, "offsetInEndSection": 1545, "text": "oxidative stress is a mechanism that generates genetic diversity in starved cells of B. subtilis, promoting stationary-phase-induced mutagenesis in this soil microorganism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 434, "text": "this type of mutagenesis is subject to regulation involving at least two of the genes that are involved in the regulation of post-exponential phase prokaryotic differentiation, i.e., comA and comK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12270822", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 526, "text": "a functional RecA protein was not required for this type of mutagenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12270822", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 992, "text": "These data suggest a role for YqjH in the generation of at least some types of stationary-phase-induced mutagenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12644484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Error-prone processing of apurinic/apyrimidinic (AP) sites by PolX underlies a novel mechanism that promotes adaptive mutagenesis in Bacillus subtilis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24914186", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Roles of YqjH and YqjW, homologs of the Escherichia coli UmuC/DinB or Y superfamily of DNA polymerases, in stationary-phase mutagenesis and UV-induced mutagenesis of Bacillus subtilis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12644484", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Mismatch repair modulation of MutY activity drives Bacillus subtilis stationary-phase mutagenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20971907", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Novel role of mfd: effects on stationary-phase mutagenesis in Bacillus subtilis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16950921", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Defects in the error prevention oxidized guanine system potentiate stationary-phase mutagenesis in Bacillus subtilis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "title" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1231, "text": "Central to stationary-phase mutagenesis in B. subtilis is the requirement for Mfd, transcription coupling repair factor, which suggests a novel mechanism from those described in other model systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22201950", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1546, "text": "In conclusion, our results support the idea that oxidative stress is a mechanism that generates genetic diversity in starved cells of B. subtilis, promoting stationary-phase-induced mutagenesis in this soil microorganism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Previous studies showed that a Bacillus subtilis strain deficient in mismatch repair (MMR; encoded by the mutSL operon) promoted the production of stationary-phase-induced mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19011023", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1445, "text": "subtilis can be generated through a novel mechanism mediated by error-prone processing of AP sites accumulated in the stationary phase by the PolX DNA polymerase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24914186", "endSection": "abstract" } ] }, { "body": "What personality traits can be evaluated with the Ten Item Personality Inventory.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22956715", "http://www.ncbi.nlm.nih.gov/pubmed/19223800" ], "ideal_answer": [ "The Ten Item Personality Inventory measures each of the five major facets of personality: openness, extroversion, conscientiousness, agreeableness and neuroticism." ], "exact_answer": [ [ "openness" ], [ "extroversion" ], [ "conscientiousness" ], [ "agreeableness" ], [ "neuroticism" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010552", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010555", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011795" ], "type": "list", "id": "56be2570ef6e39474100000d", "snippets": [ { "offsetInBeginSection": 571, "offsetInEndSection": 869, "text": "Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956715", "endSection": "abstract" }, { "offsetInBeginSection": 670, "offsetInEndSection": 816, "text": "The questionnaire measures each of the five major facets of personality: openness, extroversion, conscientiousness, agreeableness and neuroticism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19223800", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 872, "text": "DESIGN: Adoptive mothers (N = 136) were surveyed for depressive symptoms using the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Edinburgh Postnatal Depression Scale (EPDS). Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956715", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 872, "text": "Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956715", "endSection": "abstract" } ] }, { "body": "Which are the enzymes involved in the control of tubulin acetylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23798680", "http://www.ncbi.nlm.nih.gov/pubmed/21677656", "http://www.ncbi.nlm.nih.gov/pubmed/17574768", "http://www.ncbi.nlm.nih.gov/pubmed/23126280", "http://www.ncbi.nlm.nih.gov/pubmed/18697214", "http://www.ncbi.nlm.nih.gov/pubmed/22046262", "http://www.ncbi.nlm.nih.gov/pubmed/22972992", "http://www.ncbi.nlm.nih.gov/pubmed/17868033", "http://www.ncbi.nlm.nih.gov/pubmed/20520769", "http://www.ncbi.nlm.nih.gov/pubmed/22700584" ], "ideal_answer": [ "Acetyltransferase MEC-17, and deacetylases SIRT2 (Sirtuin 2), HDAC6 (histone deacetylase 6) and dTip60 are known to control the levels of tubulin acetylation." ], "exact_answer": [ [ "MEC-17" ], [ "SIRT2 (Sirtuin 2)" ], [ "HDAC6 (histone deacetylase 6)" ], [ "dTip60" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007021", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0015631", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014404", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071929", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000107", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045298" ], "type": "list", "id": "5322d3cb9b2d7acc7e000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Inhibition of HDAC6 deacetylase activity increases its binding with microtubules and suppresses microtubule dynamic instability in MCF-7 cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23798680", "endSection": "title" }, { "offsetInBeginSection": 333, "offsetInEndSection": 454, "text": "HDAC6, the tubulin deacetylase, plays a key role in maintaining typical distribution of acetylated microtubules in cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23798680", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 924, "text": "We found that whereas both pharmacological inhibition of HDAC6 as well as its depletion enhance microtubule acetylation, only pharmacological inhibition of HDAC6 activity leads to an increase in microtubule stability against cold and nocodazole-induced depolymerizing conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23798680", "endSection": "abstract" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1546, "text": "The evidence presented in this study indicated that the increased binding of HDAC6, rather than the acetylation per se, causes microtubule stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23798680", "endSection": "abstract" }, { "offsetInBeginSection": 1547, "offsetInEndSection": 1727, "text": "The results are in support of a hypothesis that in addition to its deacetylase function, HDAC6 might function as a MAP that regulates microtubule dynamics under certain conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23798680", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 684, "text": "Moreover, acetylation of \u03b1-tubulin is under the control of the acetyltransferase MEC-17 and deacetylases SIRT2 (Sirtuin 2) and HDAC6 (histone deacetylase 6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23126280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "MEC-17 deficiency leads to reduced \u03b1-tubulin acetylation and impaired migration of cortical neurons", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22972992", "endSection": "title" }, { "offsetInBeginSection": 387, "offsetInEndSection": 546, "text": "MEC-17 is a newly discovered \u03b1-tubulin acetyltransferase that has been found to play a major role in the acetylation of \u03b1-tubulin in different species in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22972992", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1516, "text": "Thus, MEC-17, which regulates the acetylation of \u03b1-tubulin, appears to control the migration and morphological transition of cortical neurons. This finding reveals the importance of MEC-17 and \u03b1-tubulin acetylation in cortical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22972992", "endSection": "abstract" }, { "offsetInBeginSection": 1248, "offsetInEndSection": 1327, "text": "NT secretion is prevented by overexpression of HDAC6, an \u03b1-tubulin deacetylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22700584", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1296, "text": "Moreover, \u03b1-tubulin acetylation levels of microtubules specifically extending into the terminal synaptic boutons are reduced in response to dTip60 HAT reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22046262", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 550, "text": "In this study, angiotensin II induced disassembly and deacetylation of \u03b1-tubulin, which were blocked by pretreatment with an angiotensin II type 1 receptor blocker losartan and a sirtuin class deacetylase inhibitor sirtinol, and by depletion of a deacetylase SIRT2 using RNA interference.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21677656", "endSection": "abstract" }, { "offsetInBeginSection": 1565, "offsetInEndSection": 1793, "text": "These data show that angiotensin II and mechanical stretch stimulate microtubule redistribution and deacetylation via SIRT2 in endothelial cells, suggesting the emerging role of SIRT2 in hypertension-induced vascular remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21677656", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 282, "text": "Tubulin is a major substrate of the cytoplasmic class II histone deacetylase HDAC6. Inhibition of HDAC6 results in higher levels of acetylated tubulin and enhanced binding of the motor protein kinesin-1 to tubulin, which promotes transport of cargoes along microtubules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20520769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Alcohol-induced alterations in hepatic microtubule dynamics can be explained by impaired histone deacetylase 6 function", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18697214", "endSection": "title" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1051, "text": "Addition of trichostatin A (TSA), an HDAC6 inhibitor, induced microtubule acetylation to the same extent as in ethanol-treated cells (approximately threefold).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18697214", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1763, "text": "Interestingly, HDAC6 from ethanol-treated cells was able to bind and deacetylate exogenous tubulin to the same extent as control, suggesting that ethanol-induced tubulin modifications prevented HDAC6 binding to endogenous microtubules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18697214", "endSection": "abstract" }, { "offsetInBeginSection": 1776, "offsetInEndSection": 1918, "text": "We propose that lower HDAC6 levels combined with decreased microtubule binding lead to increased tubulin acetylation in ethanol-treated cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18697214", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1744, "text": "The results also showed that both pan-HDAC and class-I-specific inhibitor treatment resulted in increased acetylation of histones, but only pan-HDAC inhibitor treatment resulted in increased tubulin acetylation, which is in agreement with their activity towards the HDAC6 isoform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868033", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 969, "text": "Nicotinamide but not 3-aminobenzamide, an inhibitor for poly(ADP)ribose polymerase, enhanced tubulin acetylation and resistance to axonal degeneration in cultured cerebellar granule cells from wild-type (WT) mice, suggesting that mammalian Sir2-related protein (SIRT) 2, a nicotinamide adenine dinucleotide (NAD)--dependent tubulin deacetylase, could modulate resistance to axonal degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574768", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1188, "text": "Moreover, SIRT2 overexpression abrogated microtubule hyperacetylation and resistance to axonal degeneration in these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574768", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1371, "text": "Conversely, SIRT2 knockdown by using a lentiviral vector expressing small interfering RNA, enhanced microtubule acetylation and resistance to axonal degeneration in WT granule cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574768", "endSection": "abstract" }, { "offsetInBeginSection": 1372, "offsetInEndSection": 1563, "text": "Taken together, these results suggest that SIRT2-mediated tubulin deacetylation is involved in both microtubule hyperacetylation and resistance to axonal degeneration in Wld(S) granule cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574768", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 954, "text": "Compared to control cultures, higher levels of acetylated tubulin were found in neurons treated with tubacin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20520769", "endSection": "abstract" } ] }, { "body": "Is there a relation between ANP and transcapillary albumin escape?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2952859", "http://www.ncbi.nlm.nih.gov/pubmed/9815090", "http://www.ncbi.nlm.nih.gov/pubmed/1320716", "http://www.ncbi.nlm.nih.gov/pubmed/7579054", "http://www.ncbi.nlm.nih.gov/pubmed/2173580", "http://www.ncbi.nlm.nih.gov/pubmed/2148510", "http://www.ncbi.nlm.nih.gov/pubmed/12087555", "http://www.ncbi.nlm.nih.gov/pubmed/2148091", "http://www.ncbi.nlm.nih.gov/pubmed/2958207", "http://www.ncbi.nlm.nih.gov/pubmed/2142858", "http://www.ncbi.nlm.nih.gov/pubmed/15481764", "http://www.ncbi.nlm.nih.gov/pubmed/2210073", "http://www.ncbi.nlm.nih.gov/pubmed/8065837", "http://www.ncbi.nlm.nih.gov/pubmed/10405209", "http://www.ncbi.nlm.nih.gov/pubmed/9338510", "http://www.ncbi.nlm.nih.gov/pubmed/2956451", "http://www.ncbi.nlm.nih.gov/pubmed/1837999", "http://www.ncbi.nlm.nih.gov/pubmed/8853382", "http://www.ncbi.nlm.nih.gov/pubmed/17070433", "http://www.ncbi.nlm.nih.gov/pubmed/10092997", "http://www.ncbi.nlm.nih.gov/pubmed/2526450", "http://www.ncbi.nlm.nih.gov/pubmed/9702472", "http://www.ncbi.nlm.nih.gov/pubmed/23927843", "http://www.ncbi.nlm.nih.gov/pubmed/8432776" ], "ideal_answer": [ "A possible role of ANP gene in conferring protection from nephropathy and microvascular damage in type 1 diabetes is present.\nANP infusion in healthy subjects caused a shift of plasma water and electrolytes from the circulation, with albumin escape as a secondary phenomenon" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013668", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012709", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009320", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000418" ], "type": "yesno", "id": "5321b8a39b2d7acc7e000009", "snippets": [ { "offsetInBeginSection": 2008, "offsetInEndSection": 2257, "text": "Thus, in a large ethnically homogeneous cohort of diabetic subjects, our data show: (1) a significant association of C708/T polymorphism with microalbuminuria in long-term diabetes and with both lower plasma ANP levels and widespread albumin leakage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405209", "endSection": "abstract" }, { "offsetInBeginSection": 2376, "offsetInEndSection": 2511, "text": "hese results suggest a possible role of PND gene in conferring protection from nephropathy and microvascular damage in type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405209", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1462, "text": "Moreover, the increased susceptibility of the glomerular capillaries in diabetics to ANP seems to be part of a more generalized capillary abnormality, because ANP also increases the transcapillary escape of albumin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7579054", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1433, "text": "In summary, low dose ANP infusion in healthy subjects caused a shift of plasma water and electrolytes from the circulation, with albumin escape as a secondary phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8432776", "endSection": "abstract" } ] }, { "body": "List all approved indications for Glivec", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16444286", "http://www.ncbi.nlm.nih.gov/pubmed/17024483", "http://www.ncbi.nlm.nih.gov/pubmed/21464883", "http://www.ncbi.nlm.nih.gov/pubmed/12401900", "http://www.ncbi.nlm.nih.gov/pubmed/22929880", "http://www.ncbi.nlm.nih.gov/pubmed/15671523", "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "http://www.ncbi.nlm.nih.gov/pubmed/11831069", "http://www.ncbi.nlm.nih.gov/pubmed/19584824", "http://www.ncbi.nlm.nih.gov/pubmed/22363762", "http://www.ncbi.nlm.nih.gov/pubmed/20099379", "http://www.ncbi.nlm.nih.gov/pubmed/22793867", "http://www.ncbi.nlm.nih.gov/pubmed/20032453", "http://www.ncbi.nlm.nih.gov/pubmed/22789835", "http://www.ncbi.nlm.nih.gov/pubmed/17033447", "http://www.ncbi.nlm.nih.gov/pubmed/20726677" ], "ideal_answer": [ "CML - blast crisis, in accelerated phase, and in chronic phase after interferon failure or intolerance. Glivec received orphan drug status from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development on January 31, 2001, and accelerated approval from the FDA for the above three indications on May 10, 2001.\n\nGastrointestinal stromal tumor (GIST\nTreatment with adjuvant imatinib following surgical resection of localized Kit-positive GIST\n In locally advanced inoperable patients and metastatic patients, Imatinib is the standard treatment.", "Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous neoplasm." ], "exact_answer": [ [ "Chronic myelogenous leukemia (CML)" ], [ "Gastrointestinal stromal tumor (GIST)" ], [ "Dermatofibrosarcoma protuberans (DFSP)" ] ], "type": "list", "id": "515de748298dcd4e51000023", "snippets": [ { "offsetInBeginSection": 1459, "offsetInEndSection": 1739, "text": "The limited available experience suggests that imatinib could be considered as an individualized treatment approach in severe SSc and underscores the need to identify markers for selecting particular patients, who will safely respond to therapeutic inhibition of tyrosine kinases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22789835", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous neoplasm", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21464883", "endSection": "sections.0" }, { "offsetInBeginSection": 516, "offsetInEndSection": 819, "text": "Moreover, even when surgery is utilized, there are cases where positive margins remain, in which case imatinib would be an option, often in combination with surgery. Imatinib can decrease tumor size preoperatively and help to improve postsurgical aesthetic appearance and minimize functional impairment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21464883", "endSection": "sections.0" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1619, "text": "for CML we analysed imatinib, dasatinib and nilotinib. RESULTS: Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 514, "text": "Imatinib mesylate, an orally administered kinase inhibitor that targets the Kit (CD117) protein, currently has 10 approved indications including treatment of chronic myelogenous leukemia and metastatic gastrointestinal stromal tumors (GIST). Treatment with adjuvant imatinib following surgical resection of localized Kit-positive GIST, the most recent FDA-approved indication (December 2008), has been shown to significantly improve recurrence-free survival (RFS) compared with surgical resection alone", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20726677", "endSection": "sections.0" }, { "offsetInBeginSection": 458, "offsetInEndSection": 696, "text": "Currently, there are no clinical recommendations regarding how to incorporate imatinib drug plasma monitoring in patients with either chronic myeloid leukemia or gastrointestinal stromal tumors, indications for which imatinib is approved.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20099379", "endSection": "sections.0" }, { "offsetInBeginSection": 2125, "offsetInEndSection": 2195, "text": "Imatinib was effective against GIST that were positive for KIT protein", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20032453", "endSection": "sections.0" }, { "offsetInBeginSection": 759, "offsetInEndSection": 872, "text": "The introduction of alternative therapies, such as imatinib for CML, has challenged well-established indications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19584824", "endSection": "sections.0" }, { "offsetInBeginSection": 249, "offsetInEndSection": 481, "text": "More micro-GIST are discovered with the development of investigations, rising the question of wait and see policy for some of them. In locally advanced inoperable patients and metastatic patients, Imatinib is the standard treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22793867", "endSection": "sections.0" }, { "offsetInBeginSection": 742, "offsetInEndSection": 875, "text": "The introduction of alternative therapies has challenged well-established indications such as imatinib for chronic myeloid leukaemia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16444286", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Imatinib mesylate (Gleevec, Novartis Pharmaceuticals East Manruer, NJ) received accelerated approval on May 10, 2001 for the treatment of patients with chronic myeloid leukemia (CML) in (a) chronic phase after failure of IFN-alpha therapy, (b) accelerated phase, and (c) blast crisis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15671523", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 430, "text": "Gleevec (imatinib mesylate), a highly promising new drug for the treatment of chronic myelogenous leukemia in blast crisis, in accelerated phase, and in chronic phase after interferon failure or intolerance, received orphan drug status from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development on January 31, 2001, and accelerated approval from the FDA for the above three indications on May 10, 2001.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12401900", "endSection": "sections.0" }, { "offsetInBeginSection": 1482, "offsetInEndSection": 1549, "text": "Imatinib is the first effective systemic therapy for advanced GIST.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11831069", "endSection": "sections.0" } ] }, { "body": "Which proteins induce inhibition of LINE-1 and Alu retrotransposition?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21878639", "http://www.ncbi.nlm.nih.gov/pubmed/21715505", "http://www.ncbi.nlm.nih.gov/pubmed/24367644", "http://www.ncbi.nlm.nih.gov/pubmed/19845642", "http://www.ncbi.nlm.nih.gov/pubmed/20153011", "http://www.ncbi.nlm.nih.gov/pubmed/19776130", "http://www.ncbi.nlm.nih.gov/pubmed/18597676", "http://www.ncbi.nlm.nih.gov/pubmed/24035396", "http://www.ncbi.nlm.nih.gov/pubmed/17079095" ], "ideal_answer": [ "It was demonstrated that antiretroviral restriction factors, human APOBEC3 proteins A to H, differentially inhibit LINE-1 and Alu retrotransposition. The same effect was shown to be induced by the Aicardi-Gouti\u00e8res syndrome gene product SAMHD1." ], "exact_answer": [ [ "human APOBEC3 proteins A to H" ], [ "Aicardi-Gouti\u00e8res syndrome gene product SAMHD1" ] ], "type": "list", "id": "54dfbed11388e8454a000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "APOBEC3G oligomerization is associated with the inhibition of both Alu and LINE-1 retrotransposition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24367644", "endSection": "title" }, { "offsetInBeginSection": 221, "offsetInEndSection": 374, "text": "We have previously demonstrated that antiretroviral restriction factors, human APOBEC3 (hA3) proteins (A-H), differentially inhibit L1 retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24367644", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 548, "text": "In this present study, we found that hA3 members also restrict Alu retrotransposition at differential levels that correlate with those observed previously for L1 inhibition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24367644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Gouti\u00e8res syndrome-related SAMHD1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035396", "endSection": "title" }, { "offsetInBeginSection": 223, "offsetInEndSection": 518, "text": "Here, we demonstrate that the Aicardi-Gouti\u00e8res syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035396", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 627, "text": "We also found that mutant SAMHD1s of Aicardi-Gouti\u00e8res syndrome patients are defective in LINE-1 inhibition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035396", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 750, "text": "SAMHD1 inhibits LINE-1 retrotransposition in dividing cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035396", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 322, "text": "we found that the predominantly nuclear A3B only weakly restricted infection by HIV-1, HIV-1\u0394vif, and human T-cell leukemia virus type 1 (HTLV-1), while significantly inhibiting LINE-1 retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715505", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 515, "text": "The chimeric construct A3G/B, in which the first 60 amino acids of A3B were replaced with those of A3G, restricted HIV-1, HIV-1\u0394vif, and HTLV-1 infection, as well as LINE-1 retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715505", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 386, "text": "Expression of cellular A3 proteins is sufficient for inhibition of L1 and Alu retrotransposition, but the effect of A3 proteins transferred in exosomes on retroelement mobilization is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20153011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Inhibition of LINE-1 and Alu retrotransposition by exosomes encapsidating APOBEC3G and APOBEC3F.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20153011", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "APOBEC3G oligomerization is associated with the inhibition of both Alu and LINE-1 retrotransposition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24367644", "endSection": "title" }, { "offsetInBeginSection": 196, "offsetInEndSection": 374, "text": "Previous studies revealed that the overexpression of some A3 proteins could restrict engineered human Long INterspersed Element-1 (LINE-1 or L1) retrotransposition in HeLa cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21878639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "APOBEC3 proteins inhibit LINE-1 retrotransposition in the absence of ORF1p binding.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19845642", "endSection": "title" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1137, "text": "We concluded that APOBEC3 proteins interfere indirectly with the LINE-1 retrotransposition pathway, probably through interference with RNA targeting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19845642", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 384, "text": "Expression of cellular A3 proteins is sufficient for inhibition of L1 and Alu retrotransposition, but the effect of A3 proteins transferred in exosomes on retroelement mobilization is unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20153011", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 518, "text": "Here, we demonstrate that the Aicardi-Gouti\u00e8res syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Human cytidine deaminases, including APOBEC3G (A3G) and A3F, are part of a cellular defense system against retroviruses and retroelements including non-LTR retrotransposons LINE-1 (L1) and Alu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20153011", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 751, "text": "SAMHD1 inhibits LINE-1 retrotransposition in dividing cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035396", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 385, "text": "Expression of cellular A3 proteins is sufficient for inhibition of L1 and Alu retrotransposition, but the effect of A3 proteins transferred in exosomes on retroelement mobilization is unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20153011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Selective inhibition of Alu retrotransposition by APOBEC3G.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17079095", "endSection": "title" }, { "offsetInBeginSection": 483, "offsetInEndSection": 677, "text": "Our data further indicate that APOBEC3G recognizes 7SL RNA and Alu RNA by its common structure, the Alu domain, suggesting a mechanism for APOBEC3G- mediated inhibition of Alu retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18597676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Functional analysis and structural modeling of human APOBEC3G reveal the role of evolutionarily conserved elements in the inhibition of human immunodeficiency virus type 1 infection and Alu transposition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19776130", "endSection": "title" } ] }, { "body": "Can chronological age be predicted by measuring telomere length?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23167566", "http://www.ncbi.nlm.nih.gov/pubmed/18378481" ], "ideal_answer": [ "No, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths." ], "exact_answer": "no", "type": "yesno", "id": "56d34fbcf22319765a000009", "snippets": [ { "offsetInBeginSection": 356, "offsetInEndSection": 558, "text": "Human somatic cells gradually lose telomeric repeats with age. This study investigated if one could use a correlation between telomere length and age, to predict the age of an individual from their DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18378481", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1708, "text": "Therefore, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18378481", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1194, "text": "ur results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age when exploring life history questions in natural conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23167566", "endSection": "abstract" } ] }, { "body": "What is a benefit of being g6PD-deficient?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10403541", "http://www.ncbi.nlm.nih.gov/pubmed/24152564", "http://www.ncbi.nlm.nih.gov/pubmed/23534950", "http://www.ncbi.nlm.nih.gov/pubmed/21403409", "http://www.ncbi.nlm.nih.gov/pubmed/24502194", "http://www.ncbi.nlm.nih.gov/pubmed/21929367", "http://www.ncbi.nlm.nih.gov/pubmed/15906719", "http://www.ncbi.nlm.nih.gov/pubmed/24052930", "http://www.ncbi.nlm.nih.gov/pubmed/9553792", "http://www.ncbi.nlm.nih.gov/pubmed/23696099", "http://www.ncbi.nlm.nih.gov/pubmed/22639416", "http://www.ncbi.nlm.nih.gov/pubmed/3582603", "http://www.ncbi.nlm.nih.gov/pubmed/24316370", "http://www.ncbi.nlm.nih.gov/pubmed/23479361", "http://www.ncbi.nlm.nih.gov/pubmed/24188096" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2421", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/G6PD" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18450856", "o": "Deficiency, G6PD" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1305424", "o": "G6PD deficiency" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18447746", "o": "G6PD Deficiency" } ], "ideal_answer": [ "Increased resistance to malaria, reduces the risk of coronary diseases, beneficial effect in terms of longevity" ], "exact_answer": [ "There is evidence of increased resistance to malaria." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005955", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008288", "http://www.disease-ontology.org/api/metadata/DOID:12365", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004345" ], "type": "factoid", "id": "53147b52e3eabad021000015", "snippets": [ { "offsetInBeginSection": 573, "offsetInEndSection": 730, "text": "A central position of the PPP for malaria parasites is supported by the fact that human G6PD deficiency protects to a certain degree from malaria infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22639416", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1508, "text": " The beneficial effect of thalassemia minor, sickle-cell trait, and glucose-6-phosphate dehydrogenase deficiency on survival of malaria infection may well be due to the shared feature of enhanced oxidative stress. This may inhibit parasite growth, enhance uptake of infected RBCs by spleen macrophages, and/or cause less cytoadherence of the infected cells to capillary endothelium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24316370", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1723, "text": " In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23696099", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1240, "text": " G6PD deficiency has been positively selected by malaria, and recent knowledge seems to show that it also confers an advantage against the development of cancer, reduces the risk of coronary diseases and has a beneficial effect in terms of longevity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23534950", "endSection": "abstract" }, { "offsetInBeginSection": 1632, "offsetInEndSection": 1847, "text": "G6PD enzyme activity was directly related to susceptibility to malaria in the Brazilian Amazon, where P. vivax predominates. Severe G6PDd was associated with considerable higher risk of malaria-related transfusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23479361", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 945, "text": "and G6PD (Xq28)-were associated (P \u2264 1 \u00d7 10(-6)) with RBC traits in the discovery cohort", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23696099", "endSection": "abstract" } ] }, { "body": "Describe the usefulness of Macrostomum lignano in ion channel and stem cell research", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23024658" ], "ideal_answer": [ "Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. The flatworm Macrostomum lignano is a versatile model organism for addressing these topics. Experimental tools have been developed which demonstrate how manipulation of membrane potential influences regeneration in M. lignano." ], "type": "summary", "id": "56c904745795f9a73e00001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1314, "text": "Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. Here we introduce the flatworm Macrostomum lignano as a versatile model organism for addressing these topics. We discuss biological and experimental properties of M. lignano, provide an overview of the recently developed experimental tools for this animal model, and demonstrate how manipulation of membrane potential influences regeneration in M. lignano.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024658", "endSection": "abstract" } ] }, { "body": "Is there an association between c-reactive protein concentrations and outcomes of subarachnoid hemorrhage patients? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22392113", "http://www.ncbi.nlm.nih.gov/pubmed/21757662", "http://www.ncbi.nlm.nih.gov/pubmed/19682408", "http://www.ncbi.nlm.nih.gov/pubmed/18486699", "http://www.ncbi.nlm.nih.gov/pubmed/22952245", "http://www.ncbi.nlm.nih.gov/pubmed/23208059", "http://www.ncbi.nlm.nih.gov/pubmed/22732721", "http://www.ncbi.nlm.nih.gov/pubmed/20725805", "http://www.ncbi.nlm.nih.gov/pubmed/19409001", "http://www.ncbi.nlm.nih.gov/pubmed/16369143", "http://www.ncbi.nlm.nih.gov/pubmed/11680512", "http://www.ncbi.nlm.nih.gov/pubmed/22134501", "http://www.ncbi.nlm.nih.gov/pubmed/20375501" ], "ideal_answer": [ "Yes. Higher concentrations of C-reactive protein are associated with worse outcomes of subarachnoid hemorrhage patients." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/CRP_RAT", "http://www.uniprot.org/uniprot/CRP_MESAU", "http://www.uniprot.org/uniprot/CRP_HUMAN", "http://www.uniprot.org/uniprot/CRP_CAVPO", "http://www.uniprot.org/uniprot/CRP_XENLA", "http://www.uniprot.org/uniprot/CRP_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017063", "http://www.uniprot.org/uniprot/CRP_MOUSE", "http://www.uniprot.org/uniprot/CRP_RABIT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013345" ], "type": "yesno", "id": "514cbbf9d24251bc05000065", "snippets": [ { "offsetInBeginSection": 349, "offsetInEndSection": 1003, "text": "Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow Outcome Scale; the secondary end point was the occurrence of DINDs. RESULTS: : During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow Outcome Scale score, 1-3).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23208059", "endSection": "sections.0" }, { "offsetInBeginSection": 738, "offsetInEndSection": 995, "text": "Twenty-three and 28 patients showed poor outcome and symptomatic vasospasm after SAH, respectively. Both preoperative and postoperative CRP levels were significantly higher in patients with a poor outcome compared with patients with a good outcome (P<0.05).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732721", "endSection": "sections.0" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1248, "text": "e area under the receiver operating characteristic curve of CRP measured on postoperative day 1 or 2 (CRP POD1-2) for predicting a poor clinical outcome was 0.870, and its cutoff point of 4 mg/dL had a sensitivity of 0.826 and a specificity of 0.843.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732721", "endSection": "sections.0" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1442, "text": "A high CRP level after aneurysm treatment was associated with severe neurological deterioration on admission, cerebral infarction, intracerebral hemorrhage, and surgical decompression (P<0.05).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732721", "endSection": "sections.0" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1707, "text": "CRP POD1-2, and not the preoperative CRP, was an independent factor in predicting symptomatic vasospasm (P<0.05). In patients with symptomatic vasospasm, an increase in the postoperative CRP was associated with the time profile of developing symptomatic vasospasm.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732721", "endSection": "sections.0" }, { "offsetInBeginSection": 1721, "offsetInEndSection": 1877, "text": "Postoperative CRP, especially CRP POD1-2, can be a useful prognostic factor for both poor outcome and symptomatic vasospasm in patients with aneurysmal SAH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732721", "endSection": "sections.0" }, { "offsetInBeginSection": 674, "offsetInEndSection": 929, "text": "Serum CRP levels were related to severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and Fisher grades presented statistically significant higher serum CRP levels. Patients with higher serum CRP levels had a less favorable prognosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392113", "endSection": "sections.0" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1039, "text": "Increased serum CRP levels were strongly associated with worse clinical prognosis in this study.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22392113", "endSection": "sections.0" }, { "offsetInBeginSection": 119, "offsetInEndSection": 288, "text": "After SAH, the value of C-reactive protein (CRP)--an acute phase sensitive inflammatory marker--as a prognostic factor has been poorly studied, with conflicting results.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134501", "endSection": "sections.0" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1473, "text": "Admission (18.0\u2009\u00b1\u200935.7 vs 8.5\u2009\u00b1\u20098.4 mg/l) and postoperative (41.0\u2009\u00b1\u200940.2 vs 21.1\u2009\u00b1\u200924.1 mg/l) CRP levels were higher (p\u2009<\u20090.001) in those with a poor outcome than in those with a favourable outcome, but CRP values did not predict delayed cerebral ischaemia or cerebral infarction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134501", "endSection": "sections.0" }, { "offsetInBeginSection": 1625, "offsetInEndSection": 1757, "text": "Higher increase in CRP level between admission and postoperative morning, however, independently predicted poor outcome (p\u2009=\u20090.004).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134501", "endSection": "sections.0" }, { "offsetInBeginSection": 1875, "offsetInEndSection": 1987, "text": "CRP levels correlate with outcome but do not seem to predict delayed cerebral ischaemia or infarction after SAH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134501", "endSection": "sections.0" }, { "offsetInBeginSection": 1487, "offsetInEndSection": 1617, "text": "Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21757662", "endSection": "sections.0" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1135, "text": "Intracranial hypertension was associated with an inflammatory response, indicating activation of the inflammatory cascade in the brain (ECF) and systemic circulation with high IL-6 and C-reactive protein (CRP) plasma levels after SAH, the latter associated with unfavourable outcome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19682408", "endSection": "sections.0" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1770, "text": "Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19409001", "endSection": "sections.0" }, { "offsetInBeginSection": 1918, "offsetInEndSection": 2148, "text": "Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19409001", "endSection": "sections.0" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1211, "text": "Finally, serum concentrations of ICAM-1, VCAM-1, and hsCRP during the early (P = .0055, P = .0266, and P = .0266) and late (P = .0423, P = .0041, and P = .0004) period were significantly higher in patients with DIND than in patients without DIND. CONCLUSIONS: Serum levels of ICAM-1, VCAM-1 and hsCRP during the early and late period following SAH correlate with DIND", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18486699", "endSection": "sections.0" }, { "offsetInBeginSection": 646, "offsetInEndSection": 809, "text": "CRP levels on days 5, 6, 7, and 8 were statistically significantly higher in the group of patients developing a DIND (P < 0.025, P < 0.016, P < 0.011, P < 0.0002).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16369143", "endSection": "sections.0" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1130, "text": "Overall CRP values were higher with increasing severity of the initial ictus according to the Hunt and Hess Scale and to the outcome according to the Glasgow Outcome Scale from day 3 on.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16369143", "endSection": "sections.0" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1494, "text": "The presented data do not prove that WBCs and CRP values have a direct contribution to the pathogenesis of ischemic complications following SAH, but it supports the assertion that inflammation may present a common pathogenic pathway in the development of such complications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16369143", "endSection": "sections.0" }, { "offsetInBeginSection": 1822, "offsetInEndSection": 1924, "text": "The CRP and TGF-beta1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11680512", "endSection": "sections.0" } ] }, { "body": "Which drug is benserazide usually co-administered with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23390548", "http://www.ncbi.nlm.nih.gov/pubmed/22384042", "http://www.ncbi.nlm.nih.gov/pubmed/10884518", "http://www.ncbi.nlm.nih.gov/pubmed/11166288", "http://www.ncbi.nlm.nih.gov/pubmed/17553556", "http://www.ncbi.nlm.nih.gov/pubmed/17113046", "http://www.ncbi.nlm.nih.gov/pubmed/7737328", "http://www.ncbi.nlm.nih.gov/pubmed/2760634", "http://www.ncbi.nlm.nih.gov/pubmed/16023708", "http://www.ncbi.nlm.nih.gov/pubmed/17141847", "http://www.ncbi.nlm.nih.gov/pubmed/15275774" ], "ideal_answer": [ "Co-administration of L-Dopa with carbidopa or benserazide is the most effective symptomatic treatment for Parkinson Disease (PD)." ], "exact_answer": [ "L-Dopa" ], "concepts": [ "http://www.biosemantics.org/jochem#4248923", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009934", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001545" ], "type": "factoid", "id": "52bf1f2d03868f1b06000015", "snippets": [ { "offsetInBeginSection": 327, "offsetInEndSection": 650, "text": "The present study utilizes in vivo amperometry to investigate the impact from unilateral 6-hydroxydopamine lesions and l-DOPA (4 mg/kg, including benserazide 15 mg/kg) -induced dyskinetic behavior on striatal basal extracellular glutamate concentration and potassium-evoked glutamate release in urethane-anesthetized rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390548", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 414, "text": "Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide) is the most effective symptomatic treatment for PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22384042", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 780, "text": "In experiment 1, l-DOPA-primed rats were pre-treated with Vehicle (0.9% NaCl), various doses of the partial 5-HT(1A) agonist, buspirone (0.25, 1.0 or 2.5 mg/kg, ip) or buspirone (2.5 mg/kg, ip)+the 5-HT(1A) antagonist, WAY100635 (0.5 mg/kg, ip) 5 min prior to l-DOPA (12 mg/kg+15 mg/kg benserazide, ip). R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17553556", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 640, "text": "L-DOPA induced hyperalgesia occurred after conversion to dopamine because co-administration of benserazide, a DOPA decarboxylase inhibitor, completely abolished the L-DOPA-induced hyperalgesia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17141847", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 572, "text": "First, animals were treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg, twice daily), intraperitoneally (i.p.) for 22 days. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17113046", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 537, "text": "Chronic L-DOPA-treated rats received the D1 receptor antagonist SCH23390 (0.01, 0.1, and 1.0 mg/kg; i.p.), the D2 receptor antagonist Eticlopride (0.01, 0.1, and 1.0 mg/kg; i.p.), a mixture of both antagonists (0.01, 0.1, 1.0 mg/kg each; i.p.), or vehicle 30 min prior to L-DOPA (6 mg/kg; i.p.)+Benserazide (15 mg/kg; i.p.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16023708", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 375, "text": "Nociceptive behaviors in mice after an intrathecal (i.t.) administration of substance P were evaluated. L-DOPA (i.t.) dose-dependently attenuated the substance P-induced nociceptive behaviors. Co-administration of benserazide (i.t.), a DOPA decarboxylase inhibitor, abolished the antinociceptive effect of L-DOPA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15275774", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 991, "text": "They were injected subcutaneously (s.c.) with L-DOPA methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L-DOPA/benserazide) alone or in combination with (-)-OSU6162 (1.0, 3.0, 6.0 or 10 mg/kg, s.c.)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11166288", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 806, "text": "They were injected subcutaneously (s.c.) with L-Dopa methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L-Dopa/benserazide) alone or in combination with JL-18 (at the doses of 0.1, 0.3, or 0.9 mg/kg, s.c.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10884518", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 1035, "text": "The administration of L-dopa (20 and 60 mg/kg p.o.) + benserazide (15 mg/kg p.o.) resulted in dose-dependent increase of dialysate levels of L-dopa and 3-O-methyl-DOPA. Tolcapone (30 mg/kg p.o.), given as adjunct to both doses of L-dopa, markedly enhanced the elevation or extracellular L-dopa, while it completely prevented the formation of 3-O-methyl-DOPA. In another experiment, the administration of L-dopa + benserazide (30 + 15 mg/kg p.o.) resulted in increased extracellular levels of dopamine, DOPAC, HVA and 3-methoxytyramine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7737328", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 485, "text": "In healthy subjects and in patients with parkinsonism plasma ALAAD level fell after administration of L-dopa + benserazide, but returned to previous levels within 90 min.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2760634", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 764, "text": "In a cross-sectional study blood was obtained, 2 h after dosing, from 104 patients with idiopathic parkinsonism, divided into four groups: no L-dopa treatment (group 1), L-dopa alone (group 2), L-dopa + benserazide (Madopar) (group 3) and L-dopa + carbidopa (Sinemet) (group 4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2760634", "endSection": "abstract" } ] }, { "body": "What is the inheritance pattern of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) caused by RYR2 mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17666061", "http://www.ncbi.nlm.nih.gov/pubmed/18052993", "http://www.ncbi.nlm.nih.gov/pubmed/15336972" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q9ERN6", "o": "http://linkedlifedata.com/resource/#_513945524E360021" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513945524E360021", "o": "Ryr2" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/intact/EBI-643628", "o": "http://purl.uniprot.org/uniprot/Q9ERN6" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-643628", "o": "Ryr2" }, { "p": 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"http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16610180", "o": "VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 1; CPVT1, GLN4201ARG" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1867070", "o": "http://linkedlifedata.com/resource/umls/label/A16610180" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1867070", "o": "http://linkedlifedata.com/resource/umls/label/A11961599" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11961599", "o": "RYR2, GLN4201ARG" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16610180", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16608313", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16610181", "o": "VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 1; CPVT1, ALA4860GLY" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2674258", "o": "http://linkedlifedata.com/resource/umls/label/A16610181" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2674258", "o": "http://linkedlifedata.com/resource/umls/label/A16608313" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16608313", "o": "RYR2, ALA4860GLY" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C2674258", "o": "http://linkedlifedata.com/resource/umls/label/A16608313" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16610181", "o": "OMIM" } ], "ideal_answer": [ "Autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT) was mapped to chromosome 1q42-43 with identification of pathogenic mutations in RYR2." ], "exact_answer": [ "autosomal dominant" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019837", "http://www.uniprot.org/uniprot/RYR2_RABIT", "http://www.uniprot.org/uniprot/RYR2_MOUSE", "http://www.uniprot.org/uniprot/RYR2_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.uniprot.org/uniprot/RYR2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918" ], "type": "factoid", "id": "52bf19f703868f1b06000002", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 617, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrythmogenic disease characterized by exercise--or stress--induced ventricular tachyarrythmias, syncope, or sudden death, usually in the pediatric age group. Familial occurrence has been noted in about 30% of cases. Inheritance may be autosomal dominant or recessive, usually with high penetrance. The causative genes have been mapped to chromosome 1. Mutations of the cardiac ryanodine receptor gene (RyR2) have been identified in autosomal dominant pedigrees, while calsequestrin gene (CASQ2) mutations are seen in recessive cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18052993", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 194, "text": "Previously, autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT [1]) was mapped to chromosome 1q42-43 with identification of pathogenic mutations in RYR2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17666061", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1313, "text": "Several mutations in the genes encoding RyR1 and RyR2 have been identified in autosomal dominant diseases of skeletal and cardiac muscle, such as malignant hyperthermia (MH), central core disease (CCD), catecholaminergic polymorphic ventricular tachycardia (CPVT), and arrhythmogenic right ventricular dysplasia type 2 (ARVD2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15336972", "endSection": "abstract" } ] }, { "body": "What is the INSURE procedure in premature babies.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19679893", "http://www.ncbi.nlm.nih.gov/pubmed/18841536", "http://www.ncbi.nlm.nih.gov/pubmed/20180736", "http://www.ncbi.nlm.nih.gov/pubmed/22430447", "http://www.ncbi.nlm.nih.gov/pubmed/20616570", "http://www.ncbi.nlm.nih.gov/pubmed/10218338", "http://www.ncbi.nlm.nih.gov/pubmed/17476269", "http://www.ncbi.nlm.nih.gov/pubmed/20642659", "http://www.ncbi.nlm.nih.gov/pubmed/23336160", "http://www.ncbi.nlm.nih.gov/pubmed/21506654", "http://www.ncbi.nlm.nih.gov/pubmed/22266202", "http://www.ncbi.nlm.nih.gov/pubmed/557175", "http://www.ncbi.nlm.nih.gov/pubmed/17069738", "http://www.ncbi.nlm.nih.gov/pubmed/23359581", "http://www.ncbi.nlm.nih.gov/pubmed/23320153", "http://www.ncbi.nlm.nih.gov/pubmed/20545934" ], "ideal_answer": [ "The INSURE procedure includes intubation, surfactant administration, and extubation (InSurE). It is used to treat respiratory distress syndrome in newborns.", "InSurE stands for Intubation-surfactant-extubation and is a method in the treatment of neonatal respiratory distress syndrome (NRDS)" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047928", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007234" ], "type": "summary", "id": "515db54c298dcd4e51000016", "snippets": [ { "offsetInBeginSection": 63, "offsetInEndSection": 178, "text": " intubation-surfactant-extubation (INSURE) method in the treatment of neonatal respiratory distress syndrome (NRDS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23336160", "endSection": "sections.0" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1721, "text": "INSURE method can improve the oxygenation function of the lung, decrease the incidence of VAP and shorten the duration of oxygen therapy in neonates with NRDS", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23336160", "endSection": "sections.0" }, { "offsetInBeginSection": 66, "offsetInEndSection": 113, "text": "intubation, surfactant, and extubation (InSurE)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430447", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 311, "text": "Nasal continuous positive airway pressure (NCPAP) plus intubation, surfactant, and extubation (InSurE) with the option of back-up ventilation for those infants for whom noninvasive ventilatory support failed resulted in a significant increase in survival in extremely low birth weight (ELBW) infants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430447", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "The INSURE method, which consists of an intubation-surfactant-extubation sequence, is effective in reducing the need for mechanical ventilation (MV), the duration of respiratory support, and the need for surfactant replacement in preterm infants with respiratory distress syndrome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266202", "endSection": "sections.0" }, { "offsetInBeginSection": 63, "offsetInEndSection": 115, "text": "intubation-surfactant-extubation (INSURE) procedures", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21506654", "endSection": "sections.0" }, { "offsetInBeginSection": 301, "offsetInEndSection": 374, "text": " INSURE (Intubation SURfactant Extubation) procedure in preterm neonates.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20642659", "endSection": "sections.0" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1045, "text": "INtubation-SURfactant-Extubation (INSURE) treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616570", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 242, "text": "Surfactant given during brief intubation followed by immediate extubation on nasal continuous positive airway pressure [Intubation-Surfactant-Extubation (InSurE) approach] is used to treat respiratory distress syndrome in newborns.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545934", "endSection": "sections.0" }, { "offsetInBeginSection": 120, "offsetInEndSection": 168, "text": "INSURE (intubatio-surfactant-extubation) method ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20180736", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 209, "text": "In preterm infants with respiratory distress syndrome (RDS) nasal continuous positive airway pressure (nCPAP) with the \"InSurE\" procedure (intubation, surfactant, extubation) is increasingly used. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19679893", "endSection": "sections.0" }, { "offsetInBeginSection": 92, "offsetInEndSection": 247, "text": "INSURE method ( INtubation- SURfactant- Extubation) during nasal continuous positive airway pressure for preterm infants with respiratory distress syndrome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18841536", "endSection": "sections.0" }, { "offsetInBeginSection": 48, "offsetInEndSection": 287, "text": "a method for surfactant administration by transient intubation, INSURE (i.e. INtubation SURfactant Extubation) during nasal continuous positive airway pressure (nCPAP) for moderately preterm infants with respiratory distress syndrome (RDS)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17476269", "endSection": "sections.0" }, { "offsetInBeginSection": 271, "offsetInEndSection": 392, "text": "(INSURE method: INtubation-SURfactant-Extubation) during treatment with nasal Continuous Positive Airway Pressure (CPAP).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17069738", "endSection": "sections.0" }, { "offsetInBeginSection": 380, "offsetInEndSection": 573, "text": "INSURE (Intubation-SURfactant-Extubation) approach--i.e., surfactant therapy during brief intubation, immediately followed by extubation and continuous positive airway pressure (CPAP) treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10218338", "endSection": "sections.0" }, { "offsetInBeginSection": 251, "offsetInEndSection": 301, "text": "InSurE (Intubate, Surfactant, Extubate) procedure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359581", "endSection": "sections.0" } ] }, { "body": "Which are the available biomedical text mining tools for the detection of protein-protein interactions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15719064", "http://www.ncbi.nlm.nih.gov/pubmed/23325628", "http://www.ncbi.nlm.nih.gov/pubmed/18834496", "http://www.ncbi.nlm.nih.gov/pubmed/22693219", "http://www.ncbi.nlm.nih.gov/pubmed/22595237", "http://www.ncbi.nlm.nih.gov/pubmed/19635172", "http://www.ncbi.nlm.nih.gov/pubmed/22513129", "http://www.ncbi.nlm.nih.gov/pubmed/21884822", "http://www.ncbi.nlm.nih.gov/pubmed/18204916", "http://www.ncbi.nlm.nih.gov/pubmed/18834498", "http://www.ncbi.nlm.nih.gov/pubmed/12689350", "http://www.ncbi.nlm.nih.gov/pubmed/18834492", "http://www.ncbi.nlm.nih.gov/pubmed/18508809", "http://www.ncbi.nlm.nih.gov/pubmed/18834495", "http://www.ncbi.nlm.nih.gov/pubmed/18712320", "http://www.ncbi.nlm.nih.gov/pubmed/18283029", "http://www.ncbi.nlm.nih.gov/pubmed/15998455", "http://www.ncbi.nlm.nih.gov/pubmed/19850753", "http://www.ncbi.nlm.nih.gov/pubmed/23221174", "http://www.ncbi.nlm.nih.gov/pubmed/18834500", "http://www.ncbi.nlm.nih.gov/pubmed/21106487", "http://www.ncbi.nlm.nih.gov/pubmed/21062765", "http://www.ncbi.nlm.nih.gov/pubmed/19828077", "http://www.ncbi.nlm.nih.gov/pubmed/18207462", "http://www.ncbi.nlm.nih.gov/pubmed/19234603", "http://www.ncbi.nlm.nih.gov/pubmed/20671319", "http://www.ncbi.nlm.nih.gov/pubmed/20617200", "http://www.ncbi.nlm.nih.gov/pubmed/20122157", "http://www.ncbi.nlm.nih.gov/pubmed/18237434", "http://www.ncbi.nlm.nih.gov/pubmed/22711795", "http://www.ncbi.nlm.nih.gov/pubmed/22438567", "http://www.ncbi.nlm.nih.gov/pubmed/15941473", "http://www.ncbi.nlm.nih.gov/pubmed/19594875", "http://www.ncbi.nlm.nih.gov/pubmed/18487273" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7659857", "o": "C18469" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0872079", "o": "http://linkedlifedata.com/resource/umls/label/A1883605" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1883605", "o": "protein protein interaction" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0971869", "o": "http://linkedlifedata.com/resource/umls/label/A2039412" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2039412", "o": "D025941" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2039413", "o": "Protein-Protein Interaction Maps" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2039392", "o": "D025941" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17004128", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17004128", "o": "D057225" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17004128", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17004128", "o": "Mining, Text" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A7659857", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "Protein-protein interactions (PPI) can be extracted from biomedical literature using text mining approaches. These approaches have been classified into two categories, the statistical calculation of the co-occurrence of proteins and the computational linguistic method. Moreover, bioinformatics methods based on sequence, structural, or evolutionary information have been developed to predict protein-protein interactions. The available state-of-the-art biomedical text mining tools are: eFIP (Extracting Functional Impact of Phosphorylation), a system for text mining of protein interaction networks of phosphorylated proteins; GeneView, a suite of state-of-the-art text-mining tools designed for the automated identification of protein\u2013protein interactions; PPI finder, a text mining tool for human protein-protein interactions based on computational linguistic methods. PPI Finder system consists of the Information Retrieval module and Information Extraction module; PreBIND and Textomy are two components of a biomedical literature-mining system optimized to discover protein-protein interactions using a support vector machine; BioMap system is optimized for the identification of protein-protein interactions from large biomedical literature datasets; Protopia searches for and integrates protein-protein interactions and the information about them contained in five different Protein Interaction Web Databases; STRING uses Natural Language Processing to extract a subset of semantically specified known and predicted protein-protein interactions.", "Several tools have been developed to detect protein-protein interactions (PPIs) by text mining the biomedical literature. Two main computational approaches used for this task are co-occurrence-based methods and Natural Language Processing methods. Biomedical text mining tools for PPI identification are the following (in alphabetical order): BioCreative Meta Server, BioMap, eFIP, Extracting Functional Impact of Phosphorylation, GeneView, HAPPI, Hidden Vector State model, iHop, LAITOR, OntoGene, OpenDMAP, PIE (Protein interaction information extraction system), PPI finder (Paired-PPI Finder), PPInterFinder, PPIs, PolySearch, PreBind and Textomy, Protopia, STRING, TafTalent." ], "exact_answer": [ [ "BioCreative Meta Server" ], [ "Hidden Vector State model" ], [ "iHop" ], [ "LAITOR" ], [ "OntoGene" ], [ "PIE", "Protein interaction information extraction system" ], [ "PPInterFinder" ], [ "PPIs" ], [ "TafTalent" ], [ "PolySearch" ], [ "OpenDMAP" ], [ "HAPPI" ], [ "GeneView" ], [ "PPI finder", "Paired-PPI Finder" ], [ "PreBind", "PreBIND", "Textomy" ], [ "BioMap" ], [ "eFIP", "Extracting Functional Impact of Phosphorylation" ], [ "Protopia" ], [ "STRING" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060145", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057225" ], "type": "list", "id": "5149aafcd24251bc05000045", "snippets": [ { "offsetInBeginSection": 300, "offsetInEndSection": 672, "text": "In this study, we propose a novel algorithm for extracting PPIs from literature which consists of two phases. First, we automatically categorize the data into subsets based on its semantic properties and extract candidate PPI pairs from these subsets. Second, we apply support vector machines (SVMs) to classify candidate PPI pairs using features specific for each subset.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062765", "endSection": "sections.0" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1161, "text": "The source code and scripts used in this article are available for academic use at http://staff.science.uva.nl/~bui/PPIs.zip", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062765", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "We describe a system for the detection of mentions of protein-protein interactions in the biomedical scientific literature. The original system was developed as a part of the OntoGene project", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20671319", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Extracting Protein-Protein Interactions from MEDLINE using the Hidden Vector State model", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18283029", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 284, "text": "We have constructed an information extraction system based on the Hidden Vector State (HVS) model for protein-protein interactions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18283029", "endSection": "sections.0" }, { "offsetInBeginSection": 438, "offsetInEndSection": 571, "text": "When applied in extracting protein-protein interactions, we found that it performed better than other established statistical methods", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18283029", "endSection": "sections.0" }, { "offsetInBeginSection": 1732, "offsetInEndSection": 1855, "text": "The developed BioMap system allows discovering implicit P-P interactions from large quantity of biomedical literature data.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18204916", "endSection": "sections.0" }, { "offsetInBeginSection": 669, "offsetInEndSection": 1077, "text": "In this paper we examine if P-P interactions in regenerating tissues and cells of the anuran Xenopus laevis can be discovered from biomedical literature using computational and literature mining techniques. Using literature mining techniques, we have identified a set of implicitly interacting proteins in regenerating tissues and cells of Xenopus laevis that may interact with Cdc2 to control cell division.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18204916", "endSection": "sections.0" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1560, "text": "P-P interactions that are implicitly appearing in literature can be effectively discovered using literature mining techniques.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18204916", "endSection": "sections.0" } ] }, { "body": "How thyrocyte destruction is induced in autoimmune thyroiditis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11101869", "http://www.ncbi.nlm.nih.gov/pubmed/19514601", "http://www.ncbi.nlm.nih.gov/pubmed/9886394", "http://www.ncbi.nlm.nih.gov/pubmed/11321234", "http://www.ncbi.nlm.nih.gov/pubmed/9020075" ], "ideal_answer": [ "Thyrocytes from Hashimoto's thyroiditis (HT) glands, but not from nonautoimmune thyroids, expressed Fas (CD95), therefore autonomous interaction between thyrocyte Fas (CD95) and FasL (CD95L) has been proposed as a major mechanism of thyrocyte depletion in HT. Moreover, experimental evidence has showed that Infiltrating T Lymphocytes (ITLs) do not express significant amounts of FasL, suggesting that ITLs are not directly involved in thyrocyte destruction." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:7188" ], "type": "summary", "id": "5503167be9bde69634000028", "snippets": [ { "offsetInBeginSection": 208, "offsetInEndSection": 537, "text": "These morphological findings suggested that autoreactive T-cell clones were responsible for thyrocyte destruction and hypothyroidism through effector-target cytotoxic recognition. Later, autonomous interaction between thyrocyte Fas and FasL has been proposed as a major mechanism of thyrocyte depletion in Hashimoto's thyroiditis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11321234", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 763, "text": "Here, we analyze the possible role of Fas and FasL in the pathogenesis of Hashimoto's thyroiditis. We suggest that the Fas-FasL system dictates the outcome of the autoimmune response by acting on both immune and target cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11321234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "After autoimmune inflammation, interactions between CD95 and its ligand (CD95L) mediate thyrocyte destruction in Hashimoto's thyroiditis (HT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11101869", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 943, "text": "modulation of apoptosis-related proteins by TH1 and TH2 cytokines controls thyrocyte survival in thyroid autoimmunity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11101869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Hashimoto's thyroiditis (HT) is a chronic autoimmune disease resulting from Fas-mediated thyrocyte destruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886394", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 324, "text": "Although autocrine/paracrine Fas-Fas ligand (FasL) interaction is responsible for thyrocyte cell death during the active phases of HT, the role of infiltrating T lymphocytes (ITL) in this process is still unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886394", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 744, "text": "All ITL expressed high levels of Fas and CD69, an early marker of T cell activation associated with functional Fas expression in T cells in vivo. In contrast to thyrocytes that were found to produce high levels of FasL, ITL did not express significant amounts of FasL, suggesting that ITL are not directly involved in thyrocyte destruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886394", "endSection": "abstract" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1654, "text": "These data demonstrate that ITL are not directly involved in thyrocyte cell death during HT, suggesting that autocrine/paracrine Fas-FasL interaction is a major mechanism in autoimmune thyrocyte destruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886394", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 798, "text": "Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1beta (IL-1beta), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1beta induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1beta-induced Fas expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL interactions among HT thyrocytes may contribute to clinical hypothyroidism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9020075", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1464, "text": "MECHANISM OF APOPTOSIS IN HASHIMOTO THYROIDITIS: The thyroid cell destruction characteristic of autoimmune thyroiditis can be seen as the consequence of inappropriate expression of Fas or TRAIL death pathway molecules and down-regulation of the apoptosis controlling protein Bcl-2, which may be induced by cytokines released locally by infiltrating lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19514601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "After autoimmune inflammation, interactions between CD95 and its ligand (CD95L) mediate thyrocyte destruction in Hashimotos thyroiditis (HT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11101869", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 359, "text": "Interleukin-1beta (IL-1beta), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9020075", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 536, "text": "Later, autonomous interaction between thyrocyte Fas and FasL has been proposed as a major mechanism of thyrocyte depletion in Hashimoto's thyroiditis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11321234", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 706, "text": "Exposure to IL-1beta induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1beta-induced Fas expression serves as a limiting factor for thyrocyte destruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9020075", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 707, "text": "Exposure to IL-1beta induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1beta-induced Fas expression serves as a limiting factor for thyrocyte destruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9020075", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1347, "text": "The thyroid cell destruction characteristic of autoimmune thyroiditis can be seen as the consequence of inappropriate expression of Fas or TRAIL death pathway molecules and down-regulation of the apoptosis controlling protein Bcl-2, which may be induced by cytokines released locally by infiltrating lymphocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19514601", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 818, "text": "Interferon gamma promoted caspase up-regulation and CD95-induced apoptosis in HT thyrocytes, whereas interleukin 4 and interleukin 10 protected GD thyrocytes by potent up-regulation of cFLIP and Bcl-xL, which prevented CD95-induced apoptosis in sensitized thyrocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11101869", "endSection": "abstract" } ] }, { "body": "Do A-type lamins bind euchromatin or heterochromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11953316", "http://www.ncbi.nlm.nih.gov/pubmed/18497856", "http://www.ncbi.nlm.nih.gov/pubmed/22713752", "http://www.ncbi.nlm.nih.gov/pubmed/20130288", "http://www.ncbi.nlm.nih.gov/pubmed/24153156", "http://www.ncbi.nlm.nih.gov/pubmed/19141474", "http://www.ncbi.nlm.nih.gov/pubmed/3497271", "http://www.ncbi.nlm.nih.gov/pubmed/7172763" ], "ideal_answer": [ "These data reveal that the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(\u03948-11/\u03948-11) mice", "Comparative genomic hybridization (CGH) analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and immunofluorescence localization of modified histones demonstrate that gene-rich euchromatin associates with the LA/C blebs. On the other hand, the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(\u03948-11/\u03948-11) mice" ], "exact_answer": [ "Both euchromatin and heterochromatin" ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0000792", "http://amigo.geneontology.org/amigo/term/GO:0000791", "http://amigo.geneontology.org/amigo/term/GO:0005521", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006570", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022041", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034882", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034904" ], "type": "factoid", "id": "570917bccf1c325851000015", "snippets": [ { "offsetInBeginSection": 1243, "offsetInEndSection": 1538, "text": "These data reveal that the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(\u03948-11/\u03948-11) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153156", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1031, "text": "Lmna(\u03949/\u03949) MEFs exhibit telomere shortening and heterochromatin alterations but do not activate cathepsin L-mediated degradation of 53BP1 and maintain expression of BRCA1 and RAD51", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Lamin A \u0394exon9 mutation leads to telomere and chromatin defects but not genomic instability", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153156", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11953316", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19141474", "endSection": "title" }, { "offsetInBeginSection": 667, "offsetInEndSection": 910, "text": "Comparative genomic hybridization (CGH) analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and immunofluorescence localization of modified histones demonstrate that gene-rich euchromatin associates with the LA/C blebs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19141474", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 103, "text": "Lamin A/C, caspase-6, and chromatin configuration during meiosis resumption in the mouse oocyte", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20130288", "endSection": "title" }, { "offsetInBeginSection": 678, "offsetInEndSection": 862, "text": "Our results demonstrated that these proteins were always present and that their distributions were related to oocyte maturity, determined by chromatin configuration and oocyte diameter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20130288", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 728, "text": "Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713752", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 940, "text": "Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713752", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1414, "text": "Other proteins that reversibly interact with DNA, such as the lamins and nuclear pores, may have a role in the organization of DNA into transcribable euchromatin and nontranscribable heterochromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497271", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 729, "text": "Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713752", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1223, "text": "Other proteins that reversibly interact with DNA, such as the lamins and nuclear pores, may have a role in the organization of DNA into transcribable euchromatin and nontranscribable heterochromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3497271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Role for A-type lamins in herpesviral DNA targeting and heterochromatin modulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18497856", "endSection": "title" } ] }, { "body": "Which is the most abundant membrane protein on Earth?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21718685", "http://www.ncbi.nlm.nih.gov/pubmed/24018323", "http://www.ncbi.nlm.nih.gov/pubmed/23298812", "http://www.ncbi.nlm.nih.gov/pubmed/16307124", "http://www.ncbi.nlm.nih.gov/pubmed/23933017", "http://www.ncbi.nlm.nih.gov/pubmed/19403948" ], "ideal_answer": [ "LHCII, the largest plant photosynthetic pigment-protein complex of photosystem II, is a most abundant membrane protein in living organisms and comprises approximately half of the pool of chlorophyll molecules in the biosphere." ], "exact_answer": [ "Light-harvesting pigment-protein complex of Photosystem II", "LHCII" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051380", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051205", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016020", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026901", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008566", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008565" ], "type": "factoid", "id": "5519a7d5622b194345000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "LHCII, the largest plant photosynthetic pigment-protein complex of photosystem II, is a most abundant membrane protein in living organisms and comprises approximately half of the pool of chlorophyll molecules in the biosphere. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24018323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "LHCII is the most abundant membrane protein on earth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23933017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "LHCII, the most abundant membrane protein on earth, is the major light-harvesting complex of plants. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Light-harvesting pigment-protein complex of Photosystem II (LHCII) is the largest photosynthetic antenna complex of plants and the most abundant membrane protein in the biosphere.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21718685", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 462, "text": "still very little is known about protein degradation and its regulation. The degradation of the most abundant membrane protein on Earth, the light-harvesting complex of Photosystem II (LHC II), is highly regulated under different environmental conditions, e.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16307124", "endSection": "abstract" } ] }, { "body": "Can RNASeq be used for the analysis of nascent transcripts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24225116", "http://www.ncbi.nlm.nih.gov/pubmed/24034318", "http://www.ncbi.nlm.nih.gov/pubmed/19056941", "http://www.ncbi.nlm.nih.gov/pubmed/1932016", "http://www.ncbi.nlm.nih.gov/pubmed/23934657", "http://www.ncbi.nlm.nih.gov/pubmed/22056773", "http://www.ncbi.nlm.nih.gov/pubmed/23629627", "http://www.ncbi.nlm.nih.gov/pubmed/11350041", "http://www.ncbi.nlm.nih.gov/pubmed/23307870", "http://www.ncbi.nlm.nih.gov/pubmed/729003", "http://www.ncbi.nlm.nih.gov/pubmed/24183666" ], "ideal_answer": [ "Efficient cellular fractionation improves RNA sequencing analysis of mature and nascent transcripts from human tissues. Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription. We utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://www.uniprot.org/uniprot/RNI_ECOLI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D038641", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059014", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D038621", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017423", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017421" ], "type": "yesno", "id": "53372b66d6d3ac6a34000057", "snippets": [ { "offsetInBeginSection": 458, "offsetInEndSection": 564, "text": "Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183666", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 178, "text": "Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056773", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1063, "text": "Conversely, the nuclear fraction shows an enrichment of unprocessed RNA compared with total RNA-seq, making it suitable for analysis of nascent transcripts and RNA processing dynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225116", "endSection": "abstract" } ] }, { "body": "Do RNA:DNA hybrids preferentially form in high or low GC regions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24976131", "http://www.ncbi.nlm.nih.gov/pubmed/2415514", "http://www.ncbi.nlm.nih.gov/pubmed/20729633", "http://www.ncbi.nlm.nih.gov/pubmed/18358810", "http://www.ncbi.nlm.nih.gov/pubmed/24743386" ], "ideal_answer": [ "Transcription through a GC-rich region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020862" ], "type": "yesno", "id": "56e310a151531f7e33000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Intrinsic termination signals for multisubunit bacterial RNA polymerases (RNAPs) encode a GC-rich stem-loop structure followed by a polyuridine [poly(U)] tract, and it has been proposed that steric clash of the stem-loop with the exit pore of the RNAP imposes a shearing force on the RNA in the downstream RNA:DNA hybrid, resulting in misalignment of the active site", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976131", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 737, "text": "We have observed that transcription through the GC-rich FMR1 5'UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24743386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Transcription termination by bacterial RNA polymerase (RNAP) occurs at sequences coding for a GC-rich RNA hairpin followed by a U-rich tract. We used single-molecule techniques to investigate the mechanism by which three representative terminators (his, t500, and tR2) destabilize the elongation complex (EC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18358810", "endSection": "abstract" }, { "offsetInBeginSection": 1387, "offsetInEndSection": 1736, "text": "In the 5' flanking region, nucleotides -234 to -213 encompass a GC-rich region which exhibits high homology (greater than 70%) to the 5' flanking regions of the genes of all the apolipoproteins published to date, namely, apo-A-II (-497 to -471), apo-A-I (approximately -196 to -179), apo-E (-409 to -391), and apo-C-III (approximately -116 to -103).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2415514", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1045, "text": "Recently, we demonstrated that cotranscriptional RNA\u2022DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20729633", "endSection": "abstract" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1640, "text": "Considering the extent of transcription through the human genome as well as the abundance of GC-rich and/or non-canonical DNA structure forming tandem repeats, RNA\u2022DNA hybrids may represent a common mutagenic conformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20729633", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 857, "text": "Recently, we demonstrated that cotranscriptional RNA\u2022DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20729633", "endSection": "abstract" } ] }, { "body": "Which are the most commonly reported pathological states associated with the formation of DNA G-quadruplexes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22065584", "http://www.ncbi.nlm.nih.gov/pubmed/23175609", "http://www.ncbi.nlm.nih.gov/pubmed/18426915", "http://www.ncbi.nlm.nih.gov/pubmed/16652154", "http://www.ncbi.nlm.nih.gov/pubmed/15138591", "http://www.ncbi.nlm.nih.gov/pubmed/22303960", "http://www.ncbi.nlm.nih.gov/pubmed/22673230", "http://www.ncbi.nlm.nih.gov/pubmed/23423380", "http://www.ncbi.nlm.nih.gov/pubmed/23264878", "http://www.ncbi.nlm.nih.gov/pubmed/23161677" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0071919", "o": "\"A DNA metabolic process that results in the formation of G-quadruplex DNA structures, in which groups of four guanines adopt a flat, cyclic Hoogsteen hydrogen-bonding arrangement known as a guanine tetrad or G-quartet. The stacking of several layers of G-quartets forms G-quadruplexes, in which one or more DNA single strands are assembled in parallel and/or antiparallel, with interactions that can be either intra- or intermolecular in nature.\" [GOC:sre, PMID:20098422]" }, { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0002151", "o": "\"Interacting selectively and non-covalently with G-quadruplex RNA structures, in which groups of four guanines adopt a flat, cyclic hydrogen-bonding arrangement known as a guanine tetrad.\" [PMID:18294969, PMID:18568163, PMID:19330720]" } ], "ideal_answer": [ "There is a growing recognition for the profound role of G-quadruplexes in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) were recently shown to be caused by expansion of a (GGGGCC)n/(GGCCCC)n repeat in the C9ORF72 gene. Treatment with a G-quadruplex interactive ligand was shown to achieve antifibrotic action. G-quadruplex forming sequences have also been linked with ADAM10 a primary candidate for anti-amyloidogenic activity in Alzheimer's. A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia." ], "exact_answer": [ [ "Amyotrophic lateral sclerosis (ALS)" ], [ "frontotemporal dementia (FTD)" ], [ "Alzheimer's disease" ], [ "fibrosis" ], [ "acute myeloid leukemia" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054856", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002151", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0071919", "http://www.disease-ontology.org/api/metadata/DOID:5353", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0051880", "http://www.disease-ontology.org/api/metadata/DOID:3463" ], "type": "list", "id": "51600ab3298dcd4e51000036", "snippets": [ { "offsetInBeginSection": 157, "offsetInEndSection": 324, "text": "Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) were recently shown to be caused by expansion of a (GGGGCC)n/(GGCCCC)n repeat in the C9ORF72 gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23423380", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 714, "text": "Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673230", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Up-regulating relaxin expression by G-quadruplex interactive ligand to achieve antifibrotic action", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673230", "endSection": "title" }, { "offsetInBeginSection": 1685, "offsetInEndSection": 1804, "text": "Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673230", "endSection": "sections.0" }, { "offsetInBeginSection": 368, "offsetInEndSection": 468, "text": "We identified a G-rich sequence within exon 3 of BACE1 involved in controlling splice site selection", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22303960", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "\u03b2-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the transmembrane aspartyl protease that catalyzes the first cleavage step in the proteolysis of the APP to the amyloid \u03b2-protein (A\u03b2), a process involved in the pathogenesis of Alzheimer disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22303960", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Anti-amyloidogenic processing of the amyloid precursor protein APP by \u03b1-secretase prevents formation of the amyloid-\u03b2 peptide, which accumulates in senile plaques of Alzheimer disease patients. \u03b1-Secretase belongs to the family of a disintegrin and metalloproteases (ADAMs), and ADAM10 is the primary candidate for this anti-amyloidogenic activity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22065584", "endSection": "sections.0" }, { "offsetInBeginSection": 700, "offsetInEndSection": 937, "text": "Using circular dichroism spectroscopy, we demonstrate that a G-rich region between nucleotides 66 and 94 of the ADAM10 5'-UTR forms a highly stable, intramolecular, parallel G-quadruplex secondary structure under physiological conditions", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22065584", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18426915", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16652154", "endSection": "title" }, { "offsetInBeginSection": 120, "offsetInEndSection": 304, "text": "Recently, we have demonstrated that treatment with a G-quadruplex-interactive agent, telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16652154", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15138591", "endSection": "title" }, { "offsetInBeginSection": 432, "offsetInEndSection": 612, "text": "We examined G-quadruplex interactive agent, telomestatin (SOT-095), for its ability to inhibit the proliferation of human leukemia cells, including freshly obtained leukemia cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15138591", "endSection": "sections.0" } ] }, { "body": "Are shadow enhancers associated with development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20512118", "http://www.ncbi.nlm.nih.gov/pubmed/24055171", "http://www.ncbi.nlm.nih.gov/pubmed/20797865" ], "ideal_answer": [ "Yes. Critical developmental control genes sometimes contain shadow enhancers that can be located in remote positions, including the introns of neighboring genes" ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0060484", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D041923", "http://amigo.geneontology.org/amigo/term/GO:0048541", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048788", "http://amigo.geneontology.org/amigo/term/GO:0009888", "http://amigo.geneontology.org/amigo/term/GO:0051093", "http://amigo.geneontology.org/amigo/term/GO:0048513", "http://amigo.geneontology.org/amigo/term/GO:0048569", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002658", "http://www.disease-ontology.org/api/metadata/DOID:0060040", "http://amigo.geneontology.org/amigo/term/GO:0048568", "http://amigo.geneontology.org/amigo/term/GO:0048537", "http://amigo.geneontology.org/amigo/term/GO:0048066", "http://amigo.geneontology.org/amigo/term/GO:0032502", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046468", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006803", "http://amigo.geneontology.org/amigo/term/GO:0003006", "http://amigo.geneontology.org/amigo/term/GO:0051094", "http://amigo.geneontology.org/amigo/term/GO:0043324", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002657" ], "type": "yesno", "id": "56a292ae496b62f23f000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Critical developmental control genes sometimes contain \"shadow\" enhancers that can be located in remote positions, including the introns of neighboring genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20797865", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1427, "text": "These results suggest that shadow enhancers represent a novel mechanism of canalization whereby complex developmental processes \"bring about one definite end-result regardless of minor variations in conditions\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20797865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Shadow enhancers flanking the HoxB cluster direct dynamic Hox expression in early heart and endoderm development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055171", "endSection": "title" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1480, "text": " This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development. Regulatory analysis of the HoxA complex reveals that it also has enhancers in the 3' flanking region which contain RAREs and have the potential to modulate expression in endoderm and heart tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055171", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1416, "text": "This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055171", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 642, "text": "Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns: primary enhancers located near the basal promoter and secondary, or 'shadow', enhancers located at more remote positions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20512118", "endSection": "abstract" }, { "offsetInBeginSection": 1482, "offsetInEndSection": 1797, "text": "Together, the similarities in their location, enhancer output, and dependence on retinoid signaling suggest that a conserved cis-regulatory cassette located in the 3' proximal regions adjacent to the HoxA and HoxB complexes evolved to modulate Hox gene expression during mammalian cardiac and endoderm development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055171", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1289, "text": "This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055171", "endSection": "abstract" } ] }, { "body": "Does prudent diet reduce cardiovascular risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18574045", "http://www.ncbi.nlm.nih.gov/pubmed/19656644", "http://www.ncbi.nlm.nih.gov/pubmed/9430390", "http://www.ncbi.nlm.nih.gov/pubmed/11493127", "http://www.ncbi.nlm.nih.gov/pubmed/18936332", "http://www.ncbi.nlm.nih.gov/pubmed/10597981", "http://www.ncbi.nlm.nih.gov/pubmed/22012753", "http://www.ncbi.nlm.nih.gov/pubmed/19303267", "http://www.ncbi.nlm.nih.gov/pubmed/23953031", "http://www.ncbi.nlm.nih.gov/pubmed/14972059", "http://www.ncbi.nlm.nih.gov/pubmed/22739999", "http://www.ncbi.nlm.nih.gov/pubmed/16401383" ], "ideal_answer": [ "a high adherence to prudent diet is associated with reduced risk of CVD. The adherence to prudent diet was associated to a 28% lower risk of cardiovascular mortality and a 17% lower risk of all-cause mortality in a large cohort of healthy women" ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:114", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012307", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005526", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004032" ], "type": "yesno", "id": "53319653d6d3ac6a3400003e", "snippets": [ { "offsetInBeginSection": 685, "offsetInEndSection": 902, "text": "Using this approach, large prospective studies have reported reductions in CVD risk ranging from 10 to 60% in groups whose diets can be variously classified as \u2018Healthy\u2019, \u2018Prudent\u2019, Mediterranean\u2019 or \u2018DASH compliant\u2019.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23953031", "endSection": "abstract" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1595, "text": "Our findings suggest that a heart healthy dietary pattern is associated with moderately reduced risk of MI, but not related to risk of VTE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22739999", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1165, "text": "The systematically reviewed studies reveal that a high adherence to a Mediterranean type of diet or \"prudent diet\" is associated with reduced risk of CVD and some types of cancer, even in the elderly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656644", "endSection": "abstract" }, { "offsetInBeginSection": 1399, "offsetInEndSection": 1693, "text": "In a large healthy Italian population, non-predefined dietary patterns including foods considered to be rather unhealthy, were associated with higher levels of cardiovascular risk factors, CRP and individual global CVD risk, whereas a \"prudent-healthy\" pattern was associated with lower levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19303267", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 790, "text": "We observed an inverse association between the prudent pattern and AMI, with higher levels being protective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18936332", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1314, "text": "After multivariable adjustment, the prudent diet was associated with a 28% lower risk of cardiovascular mortality (95% confidence interval [CI], 13 to 40) and a 17% lower risk of all-cause mortality (95% CI, 10 to 24) when the highest quintile was compared with the lowest quintile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18574045", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1731, "text": "Greater adherence to the prudent pattern may reduce the risk of cardiovascular and total mortality, whereas greater adherence to the Western pattern may increase the risk among initially healthy women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18574045", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1456, "text": "Composite diets (such as DASH diets, Mediterranean diet, 'prudent' diet) have been demonstrated to reduce the risk of hypertension and CHD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14972059", "endSection": "abstract" } ] }, { "body": "Is Crohn's disease (CD) linked to the consumption of refrigerated food?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14683664", "http://www.ncbi.nlm.nih.gov/pubmed/19177167", "http://www.ncbi.nlm.nih.gov/pubmed/16059694", "http://www.ncbi.nlm.nih.gov/pubmed/61441", "http://www.ncbi.nlm.nih.gov/pubmed/23444276" ], "ideal_answer": [ "All findings point to refrigeration as a potential risk factor for Crohn's disease. Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012034", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003424", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194" ], "type": "yesno", "id": "56cae40b5795f9a73e000022", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 208, "text": "Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19177167", "endSection": "abstract" }, { "offsetInBeginSection": 1382, "offsetInEndSection": 1525, "text": "This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19177167", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1207, "text": "Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19177167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "A recent published hypothesis proposed that Crohn's disease was provoked by infantile exposure to micro-organisms that can survive refrigerator temperature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16059694", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 724, "text": "This support for the hypothesis reached statistical significance for those with Crohn's disease compared to the controls (p=0.045).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16059694", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 348, "text": "Epidemiological data allow assessment of familial environmental risk factors related to western lifestyle, diet, bacteria, and domestic hygiene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14683664", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 432, "text": "All findings point to refrigeration as a potential risk factor for Crohn's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14683664", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 537, "text": "Furthermore, cold-chain development paralleled the outbreak of Crohn's disease during the 20th century. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14683664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19177167", "endSection": "abstract" }, { "offsetInBeginSection": 1254, "offsetInEndSection": 1393, "text": "Our study suggests an association between the omission of breakfast and the failure to refrigerate food with GC in the Mexican population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444276", "endSection": "abstract" } ] }, { "body": "Which drugs are included in TAS-102?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26557901", "http://www.ncbi.nlm.nih.gov/pubmed/26084259", "http://www.ncbi.nlm.nih.gov/pubmed/25776904", "http://www.ncbi.nlm.nih.gov/pubmed/25256052", "http://www.ncbi.nlm.nih.gov/pubmed/25230742", "http://www.ncbi.nlm.nih.gov/pubmed/25750295" ], "ideal_answer": [ "TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5." ], "exact_answer": [ [ "trifluridine" ], [ "tipiracil" ] ], "type": "list", "id": "56c1f000ef6e394741000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "PURPOSE: Trifluridine (TFT) is an antitumor component of a novel nucleoside antitumor agent, TAS-102, which consists of TFT and tipiracil hydrochloride (thymidine phosphorylase inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26084259", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 960, "text": "TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26557901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25750295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "PURPOSE: TAS-102 is an orally administered anticancer agent composed of \u03b1,\u03b1,\u03b1-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25776904", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 1044, "text": "Novel DNA synthesis inhibitors for the treatment of gastrointestinal malignancies include a combination of the antimetabolite TAS-102, which consists of trifluorothymidine with a thymidine phosphorylase inhibitor, and a novel micellar formulation of cisplatin NC-6004 that uses a nanotechnology-based drug delivery system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25256052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Repeated oral dosing of TAS-102 confers high trifluridine incorporation into DNA and sustained antitumor activity in mouse models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230742", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "TAS-102 is a novel oral nucleoside antitumor agent containing trifluridine (FTD) and tipiracil hydrochloride (TPI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230742", "endSection": "abstract" } ] }, { "body": "What is the most probable defect underlying triple negative breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22357256" ], "ideal_answer": [ "The most probable defect underlying triple negative breast cancer is BRCA1 dysfunction." ], "exact_answer": [ "BRCA1 dysfunction" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064726", "http://www.disease-ontology.org/api/metadata/DOID:0060081", "http://www.disease-ontology.org/api/metadata/DOID:0060076", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061325", "http://www.disease-ontology.org/api/metadata/DOID:1612", "http://www.disease-ontology.org/api/metadata/DOID:0060080", "http://www.disease-ontology.org/api/metadata/DOID:0060078", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943", "http://www.disease-ontology.org/api/metadata/DOID:0050671", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019313", "http://www.disease-ontology.org/api/metadata/DOID:5683", "http://www.disease-ontology.org/api/metadata/DOID:6741" ], "type": "factoid", "id": "52f21e8f2059c6d71c00000c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 168, "text": "We have previously reported an array comparative genomic hybridization profile that identifies triple-negative breast cancers (TNBC), with BRCA1 dysfunction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357256", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 594, "text": "BRCA1-like status was assessed in 101 patients with early-stage TNBC receiving adjuvant cyclophosphamide-based chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357256", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 749, "text": "Sixty-six tumors (65%) had a BRCA1-like profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357256", "endSection": "abstract" } ] }, { "body": "What causes erucism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19580579", "http://www.ncbi.nlm.nih.gov/pubmed/2510913", "http://www.ncbi.nlm.nih.gov/pubmed/23849585", "http://www.ncbi.nlm.nih.gov/pubmed/15361962", "http://www.ncbi.nlm.nih.gov/pubmed/22890734", "http://www.ncbi.nlm.nih.gov/pubmed/12362487", "http://www.ncbi.nlm.nih.gov/pubmed/11436711", "http://www.ncbi.nlm.nih.gov/pubmed/2907699", "http://www.ncbi.nlm.nih.gov/pubmed/12500482" ], "ideal_answer": [ "Erucism is defined as urtication by Lepidoptera larvae. It is a skin reaction to envenomation from certain poisonous caterpillar bristles. The hair on the dorsum of the last instar larvae of the moth may cause urticarial reactions (erucism) as well as eye problems and temporary blindness." ], "type": "summary", "id": "56c036afef6e394741000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Erucism is a skin reaction to envenomation from certain poisonous caterpillar bristles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23849585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, for example erucism (envenomation by caterpillars) or lepidopterism (dermatitis from moths).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "We present a case of erucism (caterpillar dermatitis) in a British serviceman deployed in Croatia on Operation Resolute. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12500482", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 295, "text": "The hair on the dorsum of the last instar larvae of the moth may cause urticarial reactions (erucism) as well as eye problems and temporary blindness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12362487", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 919, "text": "In the South of Brazil during the last years caterpillars of this butterfly caused a great number of cases of erucism including some deaths. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11436711", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 518, "text": "Urticating moths (genus Hylesia and Anaphae) protect their eggs and young caterpillars with urticating hairs, thus it is very ambiguous to label erucism as the contact dermatitis produced by caterpillar production or Lepidopterism as the contact dermatitis caused by moth urticating hairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2510913", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 163, "text": "Erucism is defined as urtication by Lepidoptera larvae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2907699", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 719, "text": "Specific syndromes caused by Lepidoptera include erucism (cutaneous reactions from contact with caterpillars, moths, or cocoons), lepidopterism (systemic involvement), ophthalmia nodosa (ocular involvement), dendrolimiasis and pararamose (each with joint symptoms relating to a specific species of caterpillar), lonomism (a severe hemorrhagic disease related to Lonomia species), and seasonal ataxia (related to ingestion of Anaphe venata). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19580579", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 1156, "text": "Specific syndromes caused by Lepidoptera include erucism (cutaneous reactions from contact with caterpillars, moths, or cocoons), lepidopterism (systemic involvement), ophthalmia nodosa (ocular involvement), dendrolimiasis and pararamose (each with joint symptoms relating to a specific species of caterpillar), lonomism (a severe hemorrhagic disease related to Lonomia species), and seasonal ataxia (related to ingestion of Anaphe venata).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19580579", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 805, "text": "Urticating moths (genus Hylesia and Anaphae) protect their eggs and young caterpillars with urticating hairs, thus it is very ambiguous to label erucism as the contact dermatitis produced by caterpillar production or Lepidopterism as the contact dermatitis caused by moth urticating hairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2510913", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 216, "text": "Erucism is defined as urtication by Lepidoptera larvae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2907699", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 162, "text": "Erucism is defined as urtication by Lepidoptera larvae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2907699", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 388, "text": "Specific syndromes caused by Lepidoptera include erucism (cutaneous reactions from contact with caterpillars,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19580579", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 519, "text": "thus it is very ambiguous to label erucism as the contact dermatitis produced by caterpillar production or Lepidopterism as the contact dermatitis caused by moth urticating hairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2510913", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 719, "text": "Specific syndromes caused by Lepidoptera include erucism (cutaneous reactions from contact with caterpillars, moths, or cocoons), lepidopterism (systemic involvement), ophthalmia nodosa (ocular involvement), dendrolimiasis and pararamose (each with joint symptoms relating to a specific species of caterpillar), lonomism (a severe hemorrhagic disease related to Lonomia species), and seasonal ataxia (related to ingestion of Anaphe venata).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19580579", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 519, "text": "Urticating moths (genus Hylesia and Anaphae) protect their eggs and young caterpillars with urticating hairs, thus it is very ambiguous to label erucism as the contact dermatitis produced by caterpillar production or Lepidopterism as the contact dermatitis caused by moth urticating hairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2510913", "endSection": "abstract" } ] }, { "body": "How does Hst5 (histatin 5) affect infections by Candida glabrata?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11442851", "http://www.ncbi.nlm.nih.gov/pubmed/7802437", "http://www.ncbi.nlm.nih.gov/pubmed/10049295", "http://www.ncbi.nlm.nih.gov/pubmed/24247141", "http://www.ncbi.nlm.nih.gov/pubmed/16495279", "http://www.ncbi.nlm.nih.gov/pubmed/9333052", "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "http://www.ncbi.nlm.nih.gov/pubmed/20140514" ], "ideal_answer": [ "Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva", "Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. We found that Hst 54-15-Spd was significantly more effective in killing C. albicans and Candida glabrata than Hst 5 alone in both planktonic and biofilm growth and that Hst 54-15-Spd retained high activity in both serum and saliva. Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 54-15), based upon our findings that C. albicans spermidine transporters are required for Hst 5 uptake and fungicidal activity.", "Our results, taken together, demonstrated that histatin-5 possessed the fungicidal activity against Candida species other than C. glabrata. ", "Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. Histatin 5, a human salivary protein with broad-spectrum antifungal activity, is remarkably ineffective against Candida glabrata. Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant. Since Hst 5 requires fungal binding to cell wall components prior to intracellular translocation, reduced Hst 5 binding to C. glabrata may be the reason for its insensitivity. Hst 5 enters C. albicans cell through polyamine transporters Dur3p and Dur31p that are uncharacterized in C. glabrata. The crucial rate limiting step is reduced uptake that can be overcome by expression of C. albicans Dur proteins in C. glabrata." ], "type": "summary", "id": "5710eec5a5ed216440000004", "snippets": [ { "offsetInBeginSection": 247, "offsetInEndSection": 389, "text": "Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247141", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 257, "text": "Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 433, "text": "Since Hst 5 requires fungal binding to cell wall components prior to intracellular translocation, reduced Hst 5 binding to C. glabrata may be the reason for its insensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 944, "text": "Hst 5 enters C. albicans cell through polyamine transporters Dur3p and Dur31p that are uncharacterized in C. glabrata. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1279, "text": "the crucial rate limiting step is reduced uptake that can be overcome by expression of C. albicans Dur proteins in C. glabrata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Histatin 5, a human salivary protein with broad-spectrum antifungal activity, is remarkably ineffective against Candida glabrata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16495279", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 498, "text": "Our results, taken together, demonstrated that histatin-5 possessed the fungicidal activity against Candida species other than C. glabrata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11442851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "The present study shows that a number of basic antifungal peptides, including human salivary histatin 5, a designed histatin analog designated dhvar4, and a peptide from frog skin, PGLa, are active against amphotericin B-resistant Candida albicans, Candida krusei, and Aspergillus fumigatus strains and against a fluconazole-resistant Candida glabrata isolate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10049295", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 886, "text": "In addition, we tested azole-resistant C. albicans and Candida glabrata strains for their susceptibilities to Hsn-5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9333052", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1727, "text": "Assessment of the candidacidal activity of Hsn-5 with the well-characterized azole-resistant strains of C. albicans and C. glabrata, however, suggested that the mode of action of histatins against Candida is distinct from that of azole-based antifungal agents because Hsn-5 kills both azole-sensitive and azole-resistant strains equally well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9333052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Histatin 5 resistance of Candida glabrata can be reversed by insertion of Candida albicans polyamine transporter-encoding genes DUR3 and DUR31.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Roles of cellular respiration, CgCDR1, and CgCDR2 in Candida glabrata resistance to histatin 5.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16495279", "endSection": "title" }, { "offsetInBeginSection": 94, "offsetInEndSection": 258, "text": "Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1259, "text": "Biofilms of C. glabrata GDH1407 and 6115/06 were less susceptible to histatin 5, with 50% RMA of 31.2 +/- 4.8 and 62.5 +/- 0.7 microM, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140514", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1279, "text": "Thus, neither C. glabrata cell surface or biofilm matrix \u03b2-1,3-glucan levels affected Hst 5 toxicity; rather the crucial rate limiting step is reduced uptake that can be overcome by expression of C. albicans Dur proteins in C. glabrata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" }, { "offsetInBeginSection": 1558, "offsetInEndSection": 1704, "text": "These results indicate that histatin 5 exhibits antifungal activity against biofilms of C. albicans and C. glabrata developed on denture acrylic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Candida albicans and Candida glabrata are predominant fungi associated with oral candidiasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" }, { "offsetInBeginSection": 1704, "offsetInEndSection": 1779, "text": "C. glabrata is significantly less sensitive to histatin 5 than C. albicans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140514", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 338, "text": "We investigated whether the distinct resistance of C. glabrata to histatin 5 is related to similar mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16495279", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 209, "text": "The authors report a case of disseminated candidiasis due to Candida glabrata with liver metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7802437", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 440, "text": "We examined antifungal activities of histatin 5 against planktonic or biofilm Candida albicans and Candida glabrata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Histatin 5 resistance of Candida glabrata can be reversed by insertion of Candida albicans polyamine transporter-encoding genes DUR3 and DUR31.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Roles of cellular respiration, CgCDR1, and CgCDR2 in Candida glabrata resistance to histatin 5.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16495279", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Histatin 5, a human salivary protein with broad-spectrum antifungal activity, is remarkably ineffective against Candida glabrata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16495279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Candida albicans and Candida glabrata are predominant fungi associated with oral candidiasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613860", "endSection": "abstract" } ] }, { "body": "Which enzyme is deficient in Krabbe disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9441867", "http://www.ncbi.nlm.nih.gov/pubmed/10448809", "http://www.ncbi.nlm.nih.gov/pubmed/11814461", "http://www.ncbi.nlm.nih.gov/pubmed/1521344", "http://www.ncbi.nlm.nih.gov/pubmed/23438514", "http://www.ncbi.nlm.nih.gov/pubmed/10090061", "http://www.ncbi.nlm.nih.gov/pubmed/16498763", "http://www.ncbi.nlm.nih.gov/pubmed/11493025", "http://www.ncbi.nlm.nih.gov/pubmed/8940268", "http://www.ncbi.nlm.nih.gov/pubmed/20301416", "http://www.ncbi.nlm.nih.gov/pubmed/2079710", "http://www.ncbi.nlm.nih.gov/pubmed/11978730", "http://www.ncbi.nlm.nih.gov/pubmed/7581365", "http://www.ncbi.nlm.nih.gov/pubmed/8577041", "http://www.ncbi.nlm.nih.gov/pubmed/85413", "http://www.ncbi.nlm.nih.gov/pubmed/19439584", "http://www.ncbi.nlm.nih.gov/pubmed/16645197", "http://www.ncbi.nlm.nih.gov/pubmed/8297359", "http://www.ncbi.nlm.nih.gov/pubmed/8281145", "http://www.ncbi.nlm.nih.gov/pubmed/9875712", "http://www.ncbi.nlm.nih.gov/pubmed/8399327", "http://www.ncbi.nlm.nih.gov/pubmed/17072020" ], "ideal_answer": [ "Galactocerebrosidase is an enzyme that is deficient in Krabbe disease (also known as globoid-cell leukodystrophy). This leads to accumulation of psychosine (galactosylsphingosine) primarily in oligodendrocytes." ], "exact_answer": [ "galactocerebrosidase" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10587", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003677", "http://www.disease-ontology.org/api/metadata/DOID:3211", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007965", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798" ], "type": "factoid", "id": "5147c8a6d24251bc05000027", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Krabbe disease is a lethal, demyelinating condition caused by genetic deficiency of galactocerebrosidase (GALC) and resultant accumulation of its cytotoxic substrate, psychosine (galactosylsphingosine), primarily in oligodendrocytes (OLs).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23438514", "endSection": "sections.0" }, { "offsetInBeginSection": 692, "offsetInEndSection": 946, "text": "In this study, we report that accumulation of endogenous psychosine under GALC deficient Krabbe conditions impedes OL differentiation process both by decreasing the expression of myelin lipids and protein and by inducing the cell death of maturating OLs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23438514", "endSection": "sections.0" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1023, "text": "In almost all individuals with Krabbe disease, galactocerebrosidase (GALC) enzyme activity is deficient (0%-5% of normal activity) in leukocytes isolated from whole heparinized blood or in cultured skin fibroblasts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301416", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "This chapter describes in detail a practical procedure for the preparation of radiolabeled galactocerebroside and its use in the assay of galactocerebrosidase (GalCase), the enzyme deficient in globoid cell leukodystrophy (Krabbe disease).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17072020", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Globoid cell leukodystrophy (Krabbe disease) is an inherited neurological disorder caused by the pathogenomic accumulation of psychosine (galactosylsphingosine), a substrate for the deficient enzyme galactocerebroside beta-galactosidase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16645197", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Krabbe disease is an extremely rare condition with an incidence of 1 in 1,00,000 live births. It is caused by deficient activity of the Iysosomal hydrolase galactosylceramide beta-galactosidase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16498763", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Globoid cell leukodystrophy (Krabbe disease) is characterized by the accumulation of a toxic metabolite, psychosine (galactosylsphingosine), which is a substrate for the deficient enzyme (galactocerebroside beta-galactosidase).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11978730", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 195, "text": "Krabbe disease (globoid-cell leukodystrophy; GLD) is caused by mutations in the GALC gene. Beta-galactocerebrosidase (GALC) is a specific beta-galactosidase which is defective in GLD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11814461", "endSection": "sections.0" }, { "offsetInBeginSection": 807, "offsetInEndSection": 970, "text": "Both galactosylceramide beta-galactosidase (GALC-GC) and GALC-PS activities were reduced by at least 85% of the normal in all but 2 of the 10 GLD patients studied.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11814461", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 160, "text": "Krabbe disease, or globoid cell leukodystrophy, is an autosomal recessive disorder caused by the deficiency of galactocerebrosidase (GALC) activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10448809", "endSection": "sections.0" }, { "offsetInBeginSection": 392, "offsetInEndSection": 522, "text": "The disease can be diagnosed by detecting the deficiency of GALC activity (less than 5% of normal) in any available tissue sample.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10448809", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Globoid cell leukodystrophy, or Krabbe disease, is a severe disorder of the peripheral and central nervous system myelin caused by deficient galactocerebrosidase (GALC) activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10090061", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Globoid cell leukodystrophy (GCL or Krabbe disease) is a recessive disease caused by mutations of the lysosomal enzyme galactocerebrosidase (GALC) and twitcher is the murine model of GCL.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9875712", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Galactocerebrosidase (GALC) is the lysosomal enzyme deficient in human and certain animal species with globoid cell leukodystrophy (GLD) or Krabbe disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9441867", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Globoid-cell leukodystrophy (GLD) is an autosomal recessive inherited disorder caused by the deficiency of galactocerebrosidase, the lysosomal enzyme responsible for the degradation of the myelin glycolipid galactocerebroside.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8940268", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Krabbe disease is an autosomal recessive inherited demyelinating disease, which is deficient in lysosomal enzyme, galactocerebrosidase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8577041", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Galactocerebrosidase (GALC) activity is deficient in all patients with globoid cell leukodystrophy (GLD).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7581365", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Human galactocerebrosidase, the enzyme deficient in Krabbe disease, was purified, through several hydrophobic column steps and gel filtration, 22,650-fold from human lymphocytes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8297359", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive disorder resulting from the deficiency of galactocerebrosidase (GALC) activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8281145", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "6-Hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside (HMGal) has been shown to be a specific fluorogenic substrate of galactocerebrosidase and to facilitate the simple enzymatic diagnosis of Krabbe disease in human patients and in twitcher mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1521344", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The inherited deficiency of galactosylceramide beta-galactosidase (E.C. 3.2.1.46: galactocerebrosidase) activity results in globoid cell leukodystrophy in humans (Krabbe disease) and in mice (twitcher mutant).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2079710", "endSection": "sections.0" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1316, "text": "The lack of complementation between Krabbe disease patient and twitcher mutant mouse cells provides further evidence that the twitcher mouse is an authentic murine model for Krabbe disease and supports the hypothesis that the mutations in both species are within the structural gene for the galactocerebrosidase enzyme.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2079710", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Galactosylceramide beta-galactosidase cross reacting material was demonstrated in brain, liver, and skin fibroblasts from patients with Krabbe disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/85413", "endSection": "sections.0" }, { "offsetInBeginSection": 385, "offsetInEndSection": 718, "text": ". In this study, LRs in the brain of the twitcher (TWI) mouse, a bona-fide model for infant variants of human globoid cell leukodystrophy or Krabbe disease, were investigated. This mouse has deficient activity of GALC (beta-galactosylceramidase) that leads to a progressive accumulation of some galactosyl-sphingolipids in the brain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19439584", "endSection": "sections.0" }, { "offsetInBeginSection": 1615, "offsetInEndSection": 1792, "text": "A GALC genotype with one deleted and one polymorphic GALC activity-reducing allele can lead to enzymatic and clinical signs of LOGLD in the absence of marked GALC-PS deficiency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11814461", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Galactocerebrosidase (GALC) is deficient in all tissues from human patients and animal models with globoid cell leukodystrophy (GLD) or Krabbe disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11493025", "endSection": "sections.0" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1739, "text": "The purification of GALC and the securing of amino acid sequence information will aid in the cloning of the GALC gene. This enzyme is deficient in human patients with Krabbe disease and several animal species.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8399327", "endSection": "sections.0" } ] }, { "body": "Are there Conserved Noncoding Elements (CNEs) in plant genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22496592", "http://www.ncbi.nlm.nih.gov/pubmed/23640124", "http://www.ncbi.nlm.nih.gov/pubmed/23110901", "http://www.ncbi.nlm.nih.gov/pubmed/18533721", "http://www.ncbi.nlm.nih.gov/pubmed/12724540", "http://www.ncbi.nlm.nih.gov/pubmed/12952874" ], "ideal_answer": [ "The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes. We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp. Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. ", "Grass genes have dramatically fewer and much smaller CNSs than mammalian genes. The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes. We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp. Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. ", "Yes. Conserved, UltraConserved and other classes of Constrained Noncoding Sequences have been found in plant genomes." ], "exact_answer": "yes", "type": "yesno", "id": "553a54babc4f83e828000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Conservation and functional element discovery in 20 angiosperm plant genomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23640124", "endSection": "title" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1127, "text": "The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23640124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Conserved noncoding sequences highlight shared components of regulatory networks in dicotyledonous plants", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23110901", "endSection": "title" }, { "offsetInBeginSection": 118, "offsetInEndSection": 359, "text": "Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23110901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Long identical multispecies elements in plant and animal genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496592", "endSection": "title" }, { "offsetInBeginSection": 318, "offsetInEndSection": 579, "text": "Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496592", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 776, "text": "In contrast, among six plant genomes, we only found nonsyntenic LIMEs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496592", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1099, "text": " Although complex LIMEs were found in both animal and plant genomes, they differed significantly in their composition and copy number", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Ultraconserved elements between the genomes of the plants Arabidopsis thaliana and rice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18533721", "endSection": "title" }, { "offsetInBeginSection": 240, "offsetInEndSection": 424, "text": "We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18533721", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 552, "text": "ultraconserved elements in plants tend to occur in clusters and locate at noncoding regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18533721", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 978, "text": "the functions of these plant ultraconserved elements and the reasons why they are practically frozen during the evolution of millions of years remain a mystery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18533721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Conserved noncoding sequences in the grasses", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12952874", "endSection": "title" }, { "offsetInBeginSection": 393, "offsetInEndSection": 634, "text": " Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12952874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Conserved noncoding sequences among cultivated cereal genomes identify candidate regulatory sequence elements and patterns of promoter evolution", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12724540", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Surveys for conserved noncoding sequences (CNS) among genes from monocot cereal species were conducted to assess the general properties of CNS in grass genomes and their correlation with known promoter regulatory elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12724540", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 977, "text": "Comparisons of orthologous maize-rice and maize-sorghum gene pairs identified 20 bp as a minimal length criterion for a significant CNS among grass genes, with few such CNS found to be conserved across rice, maize, sorghum, and barley", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12724540", "endSection": "abstract" } ] }, { "body": "Which is the localization of the RIFIN family of proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15287581", "http://www.ncbi.nlm.nih.gov/pubmed/17719658", "http://www.ncbi.nlm.nih.gov/pubmed/17255224", "http://www.ncbi.nlm.nih.gov/pubmed/17014697", "http://www.ncbi.nlm.nih.gov/pubmed/21332983", "http://www.ncbi.nlm.nih.gov/pubmed/17148488", "http://www.ncbi.nlm.nih.gov/pubmed/23259643", "http://www.ncbi.nlm.nih.gov/pubmed/16679041", "http://www.ncbi.nlm.nih.gov/pubmed/15306707", "http://www.ncbi.nlm.nih.gov/pubmed/19826486", "http://www.ncbi.nlm.nih.gov/pubmed/12438381", "http://www.ncbi.nlm.nih.gov/pubmed/23166704", "http://www.ncbi.nlm.nih.gov/pubmed/14573641", "http://www.ncbi.nlm.nih.gov/pubmed/22174947", "http://www.ncbi.nlm.nih.gov/pubmed/15939796", "http://www.ncbi.nlm.nih.gov/pubmed/19769795", "http://www.ncbi.nlm.nih.gov/pubmed/14668007" ], "ideal_answer": [ "Plasmodium falciparum rifin proteins are mainly surface-expressed. Data has shown that while A-type RIFINs were found to be associated with the parasite and transported to the surface of infected erythrocytes via Maurer's clefts, B-type RIFINs appeared to be mostly retained inside the parasite." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:620", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506" ], "type": "summary", "id": "551ae73b6b348bb82c000001", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 245, "text": " The ability of Plasmodium falciparum to undergo antigenic variation, by switching expression among protein variants encoded by multigene families, such as var, rif and stevor, is key to the survival of this parasite in the human host", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259643", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 377, "text": " The human malaria parasite Plasmodium falciparum possesses a number of multi-copy gene families, including var, rif, stevor and pfmc-2tm, which encode variant antigens believed to be expressed on the surfaces of infected erythrocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166704", "endSection": "abstract" }, { "offsetInBeginSection": 1510, "offsetInEndSection": 1642, "text": " Immunofluorescence analyses performed in parallel revealed two stage-dependent localization patterns of RIFIN, STEVOR and PfMC-2TM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166704", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 283, "text": "d variant surface antigens PfEMP1 and RIFIN ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22174947", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 277, "text": "RIFIN and STEVOR proteins are variable surface antigens uniquely found in the malaria parasites Plasmodium falciparum and P. reichenowi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21332983", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1659, "text": "parasite surface proteins such as PfEMP1, A-type RIFIN ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19826486", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 786, "text": "While A-type RIFINs were found to be associated with the parasite and transported to the surface of infected erythrocytes via Maurer's clefts, B-type RIFINs appeared to be mostly retained inside the parasite. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17719658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Variant proteins of the Plasmodium falciparum RIFIN family show distinct subcellular localization and developmental expression patterns.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17719658", "endSection": "title" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1442, "text": "Interestingly, some RIFIN variants were detected only in intracellular stages and not in merozoites, pointing to differential developmental expression patterns for distinct members of this large protein family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17719658", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 749, "text": "At least three groups of antigens, P. falciparum erythrocyte membrane protein 1 (PfEMP1)/ RIFIN/SURFIN, P. falciparum histidine-rich protein 2 (PfHRP2), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17255224", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 579, "text": "This catalog includes large families of predicted 2 transmembrane (2TM) proteins, including the Rifin, Stevor and Pfmc-2TM superfamilies, of which each possesses a region of extensive sequence diversity across paralogs and between isolates that is confined to a proposed surface-exposed loop on the infected erythrocyte", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17148488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "RIFINs are clonally variant antigens expressed in Plasmodium falciparum. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17014697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "RIFIN proteins belong to the largest Plasmodium falciparum multicopy family of variant surface antigens (VSA) expressed by infected erythrocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16679041", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1046, "text": "SURFIN4.2 not only was found cotransported with PfEMP1 and RIFIN to the IE surface, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15939796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Antibodies to rifin: a component of naturally acquired responses to Plasmodium falciparum variant surface antigens on infected erythrocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15306707", "endSection": "title" }, { "offsetInBeginSection": 845, "offsetInEndSection": 906, "text": "In contrast to other known PIESPs, such as PfEMP1 and Rifin, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15287581", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 292, "text": "We here present data revealing the existence of a unique common pathway for the surface bound traffic of the clonally variant antigens, repeated-interspersed-antigen (RIFINS) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14668007", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 527, "text": " rifin proteins (RIF proteins), belonging to the largest known family of variable infected erythrocyte surface-expressed proteins, are also naturally immunogenic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12438381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Plasmodium falciparum rifin proteins, belonging to the largest known family of variable infected-erythrocyte surface-expressed proteins encoded by rif genes, were recently shown to be capable of inducing a strong immune response in P. falciparum-infected adults living in an area in Gabon where malaria is endemic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14573641", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 518, "text": "RIFIN products are targets for the human immune response and contribute to the antigenic variability of the parasite. They are transmembrane proteins grouped into two sub-families (RIF_A and RIF_B). Although recent data show that RIF_A and RIF_B have different sub-cellular localisations and possibly different functions, the same structural organisation has been proposed for members of the two sub-families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19769795", "endSection": "abstract" } ] }, { "body": "What are the current treatments for generalised anxiety disorder in teenagers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18341545", "http://www.ncbi.nlm.nih.gov/pubmed/23404595", "http://www.ncbi.nlm.nih.gov/pubmed/20429947", "http://www.ncbi.nlm.nih.gov/pubmed/16675030", "http://www.ncbi.nlm.nih.gov/pubmed/12108800" ], "ideal_answer": [ "Cognitive-behavioral treatment (CBT) - both in individual and in group treatment\nRandomised, placebo controlled trials have found Sertraline efficacious for GAD in adults, children and adolescents.\nWhile both CBT and SSRIs are beneficial, some evidence suggests that the effects of CBT may be more long lasting." ], "exact_answer": [ [ "Cognitive-behavioral treatment (CBT)", "CBT", "group treatment", "manualised cognitive-behavioural therapy, FRIENDS" ], [ "Sertraline", "SSRI" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000293", "http://www.disease-ontology.org/api/metadata/DOID:2030", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001007", "http://www.disease-ontology.org/api/metadata/DOID:14320", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001008" ], "type": "list", "id": "515db20e298dcd4e51000014", "snippets": [ { "offsetInBeginSection": 632, "offsetInEndSection": 729, "text": "49.3% of the youths with depression had comorbid conditions: anxiety disorders in 23.37% of cases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23404595", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 334, "text": "To evaluate the feasibility and effectiveness of a school-based group cognitive-behavioral treatment (CBT) for anxiety disorders with African-American adolescents. METHODS: Twelve adolescents (mean age = 15.6 years) with anxiety disorders were randomly assigned to CBT (n = 6) or a group attention-support control condition", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12108800", "endSection": "sections.0" }, { "offsetInBeginSection": 721, "offsetInEndSection": 1073, "text": "At posttreatment and among those who attended more than one treatment session, 3/4 adolescents in CBT no longer met diagnostic criteria for their primary anxiety disorder, compared with 1/5 in AS-Control. Clinician ratings of impairment and self-report levels of overall anxiety were significantly lower at posttreatment in CBT compared with AS-Control", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12108800", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 443, "text": "The present study compares an individual versus a group format in the delivery of manualised cognitive-behavioural therapy (FRIENDS) for children with anxiety disorders. Clinically referred children (aged 8 to 12) diagnosed with Separation Anxiety Disorder (n = 52), Generalised Anxiety Disorder (n = 37), Social Phobia (n = 22) or Specific Phobia (n = 16) were randomly assigned to individual (n = 65) or group (n = 62) treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18341545", "endSection": "sections.0" }, { "offsetInBeginSection": 683, "offsetInEndSection": 986, "text": "Forty-eight percent of the children in the individual versus 41% in the group treatment were free of any anxiety disorder at post-treatment; 62% versus 54% were free of their primary anxiety disorder. Regression analyses showed no significant difference in outcome between individual and group treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18341545", "endSection": "sections.0" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1203, "text": "Children improved in both conditions. Choice between treatments could be based on pragmatic considerations such as therapeutic resources, referral rates, and the preference of the parents and the child.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18341545", "endSection": "sections.0" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1563, "text": "All child anxiety disorders were associated with several forms of anxiety disorder in the mother. Some specificity in the form of anxiety disorder in the child and the mother was apparent for social phobia and separation anxiety disorder. The findings have implications for the management of child anxiety.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675030", "endSection": "sections.0" } ] }, { "body": "Can tetracycline affect tooth formation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1410257", "http://www.ncbi.nlm.nih.gov/pubmed/3855899", "http://www.ncbi.nlm.nih.gov/pubmed/5447715", "http://www.ncbi.nlm.nih.gov/pubmed/6829791", "http://www.ncbi.nlm.nih.gov/pubmed/737550" ], "ideal_answer": [ "Tetracycline is incorporated in the teeth during their formation and leads to their permanent staining. A definite relationship between total dosage and staining and duration of administration and staining was established; the condition occurred with greater frequency (in more than one-third of the children) when the total dosage exceeded 3 g. or the duration of treatment was longer than 10 days." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4272839", "http://www.disease-ontology.org/api/metadata/DOID:1091", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013752", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013754", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014070", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014071", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014076" ], "type": "yesno", "id": "530cf4fe960c95ad0c000009", "snippets": [ { "offsetInBeginSection": 149, "offsetInEndSection": 379, "text": "he results of that study, reported earlier (Rebich et al., 1983), indicated that over one-fifth of the American Indian children had discoloration of the dentition due to ingestion of tetracycline during the years of tooth formatio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3855899", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 184, "text": "ale Wistar rats prelabeled with tetracycline to mark surfaces of bone and tooth formation-mineralization were placed into orbit for 18.5 days aboard the Soviet COSMOS-1129 Biosatellit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6829791", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 360, "text": "It was concluded that the increased tetracycline incorporation reflected a higher rate of mineralization associated with faster tooth formation in the unimpeded toot", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/737550", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 237, "text": "n this investigation an attempt has been made to determine the relationship between the staining of permanent teeth by tetracycline administered during the period of tooth formation with the dosage of the drug and the duration of therap", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/5447715", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 787, "text": " definite relationship between total dosage and staining and duration of administration and staining was established; the condition occurred with greater frequency (in more than one-third of the children) when the total dosage exceeded 3 g. or the duration of treatment was longer than 10 days", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/5447715", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 292, "text": "This case report suggests the possibility that discoloration from tetracycline may not be limited to tooth development in the child, but may also affect the adult dentition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1410257", "endSection": "abstract" } ] }, { "body": "Is there any genetic determinant of hair pigmentation that could be useful in forensic analyses?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "http://www.ncbi.nlm.nih.gov/pubmed/19016241", "http://www.ncbi.nlm.nih.gov/pubmed/22670867", "http://www.ncbi.nlm.nih.gov/pubmed/20158590", "http://www.ncbi.nlm.nih.gov/pubmed/24098679", "http://www.ncbi.nlm.nih.gov/pubmed/19414162", "http://www.ncbi.nlm.nih.gov/pubmed/23703035", "http://www.ncbi.nlm.nih.gov/pubmed/17316231", "http://www.ncbi.nlm.nih.gov/pubmed/22556244", "http://www.ncbi.nlm.nih.gov/pubmed/22709892", "http://www.ncbi.nlm.nih.gov/pubmed/19208107", "http://www.ncbi.nlm.nih.gov/pubmed/19297406", "http://www.ncbi.nlm.nih.gov/pubmed/19384953", "http://www.ncbi.nlm.nih.gov/pubmed/19083738", "http://www.ncbi.nlm.nih.gov/pubmed/21197618", "http://www.ncbi.nlm.nih.gov/pubmed/22464347", "http://www.ncbi.nlm.nih.gov/pubmed/19291462" ], "ideal_answer": [ "Yes, there are at least 12 genes associated with human hair color variation such as: TYR, TYRP1, OCA2, SLC45A2, SLC24A5, MC1R, ASIP and KITLG." ], "exact_answer": [ "Yes, there are at least 12 genes associated with human hair color variation such as: TYR, TYRP1, OCA2, SLC45A2, SLC24A5, MC1R, ASIP and KITLG." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005823", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006197", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003116", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006200", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006202", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005826" ], "type": "factoid", "id": "54f60ea05f206a0c06000009", "snippets": [ { "offsetInBeginSection": 661, "offsetInEndSection": 769, "text": "a recent paper has reported the genetic determination of eye and hair color in samples up to 800 years old. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23703035", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 542, "text": " Here, we demonstrate that human hair color is predictable from DNA variants with similarly high accuracies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21197618", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 724, "text": "12 genes previously associated with human hair color variation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21197618", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 470, "text": " several key pigmentation genes have been characterised, in particular the melanocortin 1 receptor gene (MC1R). Here, the function and known mutations of MC1R and other human pigmentation genes including ASIP, MATP, SLC24A5, TYR, TYRP1 and OCA2 are outlined, and a forensic test based on MC1R SNPs presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19083738", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 278, "text": "Recent studies have proved that there is a significant association between some genetic variants of the melanocortin 1 receptor (MC1R) gene and red hair color.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17316231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "We describe a minisequencing protocol for screening DNA samples for the presence of 12 mutations in the human melanocortin 1 receptor gene (MC1R), eight of which are associated with the red hair phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19208107", "endSection": "title" }, { "offsetInBeginSection": 592, "offsetInEndSection": 859, "text": "Several genome-wide association studies for pigmentation have now been conducted and identified single nucleotide polymorphism (SNP) markers in known, TYR, TYRP1, OCA2, SLC45A2, SLC24A5, MC1R, ASIP, KITLG and previously unknown SLC24A4, IRF4, TPCN2, candidate genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297406", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 206, "text": " five red hair colour (RHC) MC1R alleles, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22464347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Naturally blond hair is rare in humans and found almost exclusively in Europe and Oceania. Here, we identify an arginine-to-cysteine change at a highly conserved residue in tyrosinase-related protein 1 (TYRP1) as a major determinant of blond hair in Solomon Islanders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22556244", "endSection": "abstract" } ] }, { "body": "What is the suggested clinical management of Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22675616", "http://www.ncbi.nlm.nih.gov/pubmed/12525204", "http://www.ncbi.nlm.nih.gov/pubmed/23146055" ], "ideal_answer": [ "Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential.In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity", "Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential. Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity. In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. ", "Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential.", "Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity. In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. " ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "summary", "id": "54f2f81664850a5854000003", "snippets": [ { "offsetInBeginSection": 636, "offsetInEndSection": 810, "text": "Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146055", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 280, "text": "Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22675616", "endSection": "abstract" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1782, "text": "In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525204", "endSection": "abstract" } ] }, { "body": "Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) cause sudden cardiac death?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19631908", "http://www.ncbi.nlm.nih.gov/pubmed/20301466", "http://www.ncbi.nlm.nih.gov/pubmed/22307399", "http://www.ncbi.nlm.nih.gov/pubmed/23040497", "http://www.ncbi.nlm.nih.gov/pubmed/20361477", "http://www.ncbi.nlm.nih.gov/pubmed/23683917", "http://www.ncbi.nlm.nih.gov/pubmed/19564966", "http://www.ncbi.nlm.nih.gov/pubmed/22481011", "http://www.ncbi.nlm.nih.gov/pubmed/24136861", "http://www.ncbi.nlm.nih.gov/pubmed/16001794", "http://www.ncbi.nlm.nih.gov/pubmed/15913575", "http://www.ncbi.nlm.nih.gov/pubmed/23954267", "http://www.ncbi.nlm.nih.gov/pubmed/22068070", "http://www.ncbi.nlm.nih.gov/pubmed/20676041", "http://www.ncbi.nlm.nih.gov/pubmed/19863545", "http://www.ncbi.nlm.nih.gov/pubmed/21292648", "http://www.ncbi.nlm.nih.gov/pubmed/23908839", "http://www.ncbi.nlm.nih.gov/pubmed/23094885", "http://www.ncbi.nlm.nih.gov/pubmed/24062688", "http://www.ncbi.nlm.nih.gov/pubmed/18483626" ], "ideal_answer": [ "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016757", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003643", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016265", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003645", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002423" ], "type": "yesno", "id": "530cf4fe960c95ad0c000003", "snippets": [ { "offsetInBeginSection": 533, "offsetInEndSection": 774, "text": "Here we refine our approach, and apply it to novel variants found in 2266 patients across two large cohorts with inherited sudden death syndromes, namely catecholaminergic polymorphic ventricular tachycardia (CPVT) or Brugada syndrome (BrS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136861", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 166, "text": "Calsequestrin-associated catecholaminergic polymorphic ventricular tachycardia (CPVT2) can cause sudden death in young individuals in response to stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23908839", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 556, "text": "In many cases the cause of death can be elucidated by medico-legal autopsy, however, a significant number of these cases remain unexplained despite a detailed postmortem investigation and are labeled as sudden unexplained death (SUD). Post-mortem genetic testing, so called molecular autopsy, revealed that primary arrhythmogenic disorders including long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) may account for a certain number of these cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23683917", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 497, "text": "We report a family with repeat events of sudden cardiac death and recurrent ventricular fibrillation in a teenage girl, where autopsy data and clinical investigations were inconclusive. The diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was established only following finding a gene mutation in the cardiac ryano", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23094885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040497", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1287, "text": "In conclusion, patients with CASQ2-associated CPVT should be recommended to receive ICDs to prevent sudden death when medical therapy is not effective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22481011", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 997, "text": " Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) yield no evidence to be found at autopsy, leaving coroners, medical examiners, and forensic pathologists only to speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22307399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068070", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1381, "text": "We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21292648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20676041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20361477", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 544, "text": "Early detection of CPVT is crucial because opportune medical intervention prevents sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20361477", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1065, "text": " If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. Sudden death may be the first manifestation of the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20301466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Hereditary non-structural diseases such as catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT, and the Brugada syndrome as well as structural disease such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) cause a significant percentage of sudden cardiac deaths in the young", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863545", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1398, "text": "Patients with CPVT present with exercise-induced syncope and sudden cardiac death but normal resting electrocardiograms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19631908", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 974, "text": "Although structural cardiovascular abnormalities explain most cases of sudden cardiac death in young people, the cause of death remains unexplained after autopsy in 10% to 30% of cases. Potentially lethal ion channel disorders (channelopathies) such as the long QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and the Brugada syndrome (BrS) may account for at least one-third of these unexplained cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19564966", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1307, "text": "Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483626", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 838, "text": "The inherited arrhythmogenic diseases associated with the transmembranous ionic channels, anchoring proteins or intracellular calcium regulating proteins are thought to be responsible for sudden cardiac death in infants, children, and young adults who have structurally normal hearts. Recent genetic analyses have identified congenital diseases such as the long-QT syndrome (LQTS), the Jervell and Lange-Nielsen syndrome (JLNS), the Brugada syndrome (BrS), the short-QT syndrome (SQTS), the arrhythmogenic right ventricular cardiomyopathy type 2 (ARVC2), and the catecholamine-induced polymorphic ventricular tachycardia (CPVT) /familial polymorphic ventricular tachycardia (FPVT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16001794", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1019, "text": "At least some cases of sudden, unexplained death in young individuals may be ascribed to CPVT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15913575", "endSection": "abstract" } ] }, { "body": "Does Apolipoprotein E (ApoE) have anti-inflammatory activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23963646", "http://www.ncbi.nlm.nih.gov/pubmed/22197603", "http://www.ncbi.nlm.nih.gov/pubmed/22326991" ], "ideal_answer": [ "Yes. ApoE has anti-inflammatory activity" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/APOE_CANFA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050727", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050728", "http://www.uniprot.org/uniprot/APOE_MACMU", "http://www.uniprot.org/uniprot/APOE_RABIT", "http://www.uniprot.org/uniprot/APOE_GORGO", "http://www.uniprot.org/uniprot/APOE_HUMAN", "http://www.uniprot.org/uniprot/APOE_SAISC", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001057", "http://www.uniprot.org/uniprot/APOE_HYLLA", "http://www.uniprot.org/uniprot/APOE_PANTR", "http://www.uniprot.org/uniprot/APOE_PONPY", "http://www.uniprot.org/uniprot/APOE_TUPGL", "http://www.uniprot.org/uniprot/APOE_MOUSE", "http://www.uniprot.org/uniprot/APOE_PAPAN", "http://www.uniprot.org/uniprot/APOE_RAT", "http://www.uniprot.org/uniprot/APOE_MACFA", "http://www.uniprot.org/uniprot/APOE_CAVPO", "http://www.uniprot.org/uniprot/APOE_PIG", "http://www.uniprot.org/uniprot/APOE_ZALCA", "http://www.uniprot.org/uniprot/APOE_BOVIN", "http://www.uniprot.org/uniprot/APOE_SHEEP" ], "type": "yesno", "id": "530cf4fe960c95ad0c000002", "snippets": [ { "offsetInBeginSection": 2, "offsetInEndSection": 396, "text": " have previously reported that apolipoprotein E (apoE), a protein component of very-low-density lipoproteins (VLDL) and high-density lipoproteins and a potent plasma-borne atheroprotective factor, exerts anti-inflammatory activity in macrophages by switching the activation profile from M1 (\"classic\") to M2 (\"alternative\") in a process involving signaling via low-density lipoprotein receptor ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23963646", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 248, "text": "anti-inflammatory activity in macrophages ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23963646", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 360, "text": "Small peptides corresponding to the receptor-binding region of apoE mimic the anti-inflammatory activity of the apoE ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22326991", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 312, "text": "Apolipoprotein (apo) E-containing high-density lipoprotein (HDL) has antioxidant, anti-inflammatory and anti-atherogenic properties", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197603", "endSection": "abstract" } ] }, { "body": "Which drugs acting via bradykinin system are effective for treatment of ACE-inhibitor-induced angioedema?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24565614", "http://www.ncbi.nlm.nih.gov/pubmed/20922352" ], "ideal_answer": [ "Icatibant and ecallantide are medication acting via bradykinin system that are used for treatment of ACE-inhibitor-induced angioedema." ], "exact_answer": [ [ "icatibant" ], [ "ecallantide" ] ], "type": "list", "id": "54cf6d40f693c3b16b00000e", "snippets": [ { "offsetInBeginSection": 983, "offsetInEndSection": 1206, "text": "Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24565614", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 539, "text": "A patient with acute ACE inhibitor-induced angioedema was treated with icatibant, a specific bradykinin B2 receptor antagonist approved for the treatment of hereditary angioedema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20922352", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 538, "text": "A patient with acute ACE inhibitor-induced angioedema was treated with icatibant, a specific bradykinin B2 receptor antagonist approved for the treatment of hereditary angioedema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20922352", "endSection": "abstract" } ] }, { "body": "Is the ACE inhibitor indicated for lung cancer treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18837885", "http://www.ncbi.nlm.nih.gov/pubmed/22300564" ], "ideal_answer": [ "No, the angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents. On the contrary, it has been suggested that they decrease the risk of some cancers, although available data are conflicting. One study proposes that captopril could be a promising option for the treatment of lung cancer. Furthermore, angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models" ], "exact_answer": "no", "concepts": [ "http://www.uniprot.org/uniprot/ACE_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.uniprot.org/uniprot/ACE_THETS", "http://www.uniprot.org/uniprot/ACE_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:3683", "http://www.uniprot.org/uniprot/ACE_CHICK", "http://www.disease-ontology.org/api/metadata/DOID:1324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000806", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008175", "http://www.disease-ontology.org/api/metadata/DOID:850", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008171", "http://www.uniprot.org/uniprot/ACE_BOVIN", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.uniprot.org/uniprot/ACE_HAEIX", "http://www.uniprot.org/uniprot/ACE_RABIT", "http://www.uniprot.org/uniprot/ACE_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008168" ], "type": "yesno", "id": "530cf4fe960c95ad0c000005", "snippets": [ { "offsetInBeginSection": 104, "offsetInEndSection": 311, "text": "The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18837885", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1561, "text": "Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18837885", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 1181, "text": "In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18837885", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 697, "text": "Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P= 0.088). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18837885", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 135, "text": "Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22300564", "endSection": "abstract" }, { "offsetInBeginSection": 2023, "offsetInEndSection": 2147, "text": "ACE inhibitors may decrease the incidence of radiation pneumonitis in patients receiving thoracic radiation for lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22300564", "endSection": "abstract" } ] }, { "body": "Which forms of cancer is the Tpl2 gene associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21267413", "http://www.ncbi.nlm.nih.gov/pubmed/23457529", "http://www.ncbi.nlm.nih.gov/pubmed/23064365", "http://www.ncbi.nlm.nih.gov/pubmed/15575964", "http://www.ncbi.nlm.nih.gov/pubmed/20935675", "http://www.ncbi.nlm.nih.gov/pubmed/22451924" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3003", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/TPL2" } ], "ideal_answer": [ "Tpl2/Map3K8, also known as tumor progression locus 2 has been identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. Types of cancer associated with Tpl2 include skin and epithelial cancers, ADI prostate cancer, gastric and colon adenocarcinomas, colitis-associated cancer (CAC), breast cancer, Hodgkin lymphomas, nasopharyngeal carcinomas and several types of T-cell neoplasias." ], "exact_answer": [ [ "Skin cancer" ], [ "ADI prostate cancer" ], [ "gastric adenocarcinoma" ], [ "colon adenocarcinoma" ], [ "colitis-associated cancer (CAC)" ], [ "breast cancer" ], [ "Hodgkin lymphoma" ], [ "nasopharyngeal carcinoma" ], [ "T-cell neoplasia" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.uniprot.org/uniprot/M3K8_RAT" ], "type": "list", "id": "515bf6d6298dcd4e51000004", "snippets": [ { "offsetInBeginSection": 1344, "offsetInEndSection": 1485, "text": "These findings establish a mesenchyme-specific role for Tpl2 in the regulation of HGF production and suppression of epithelial tumorigenesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064365", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Tpl2 regulates intestinal myofibroblast HGF release to suppress colitis-associated tumorigenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064365", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Tpl2 ablation promotes intestinal inflammation and tumorigenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451924", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20935675", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 281, "text": " Previously identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20935675", "endSection": "sections.0" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1390, "text": "These studies indicate that Tpl2 may serve more as a tumor suppressor than as an oncogene in chemically induced skin carcinogenesis, with its absence contributing to both tumorigenesis and inflammation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20935675", "endSection": "sections.0" } ] }, { "body": "What are the indications for hydrochlorothiazide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23808745", "http://www.ncbi.nlm.nih.gov/pubmed/21718097", "http://www.ncbi.nlm.nih.gov/pubmed/21974759", "http://www.ncbi.nlm.nih.gov/pubmed/9421695", "http://www.ncbi.nlm.nih.gov/pubmed/23136355", "http://www.ncbi.nlm.nih.gov/pubmed/8227469", "http://www.ncbi.nlm.nih.gov/pubmed/23767455", "http://www.ncbi.nlm.nih.gov/pubmed/23116225", "http://www.ncbi.nlm.nih.gov/pubmed/22490507" ], "ideal_answer": [ "Hydrochlorothiazide is a diuretic, often used in combination with others. Hydrochlorothiazide are used to treat hypertension. Hydrochlorothiazide has been shown to decrease diastolic blood pressure." ], "exact_answer": [ [ "diuretic" ], [ "hypertension" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4249423", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006852" ], "type": "list", "id": "530cf4fe960c95ad0c000007", "snippets": [ { "offsetInBeginSection": 553, "offsetInEndSection": 687, "text": "The most frequently used diuretic in combination is again hydrochlorothiazide, which is combined with reninangiotensin system blockers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23808745", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1073, "text": "Also a combination of two diuretics is popular -\u200a mainly hydrochlorothiazide + amiloride", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23808745", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 166, "text": "article gives an overview of the risk factors for hypertension and the appropriate indication for using a fixed combination of telmisartan and hydrochlorothiazide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23767455", "endSection": "abstract" }, { "offsetInBeginSection": 1576, "offsetInEndSection": 1782, "text": "Hydrochlorothiazide 25-200 mg daily, chlorothiazide 500 mg twice daily, and indapamide 2.5 mg daily provided long-term blood pressure reduction in patients with severe renal disease who were not on dialysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23136355", "endSection": "abstract" }, { "offsetInBeginSection": 1828, "offsetInEndSection": 2094, "text": "This review provides an overview of the efficacy and safety of antihypertensive therapy based on olmesartan medoxomil\u2009\u00b1\u2009hydrochlorothiazide and amlodipine/olmesartan medoxomil in high-risk patient populations enrolled in studies that reported ambulatory BP endpoints", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23116225", "endSection": "abstract" }, { "offsetInBeginSection": 1746, "offsetInEndSection": 1882, "text": "In this regard, ARB-based SPCs are available in combination with the diuretic, hydrochlorothiazide (HCTZ) or the calcium CCB, amlodipine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22490507", "endSection": "abstract" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1312, "text": "Telmisartan has a favourable safety and tolerability profile, and has demonstrated efficacious and long-lasting 24-hour BP reductions, whether as monotherapy or in combination with hydrochlorothiazide or amlodipine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21718097", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 623, "text": "The combination of irbesartan and hydrochlorothiazide resulted in additive antihypertensive effects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9421695", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 561, "text": "Patients with stable hypertension, not taking antihypertensive or NSAID medications, were treated with HCTZ 50 mg/day", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8227469", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 173, "text": "is study determined the effect of nonsteroidal anti-inflammatory drug (NSAID) administration on blood pressure in hypertensive patients taking hydrochlorothiazide (HCTZ). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8227469", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1050, "text": "Hydrochlorothiazide treatment decreased diastolic blood pressure to 83.1 +/- 5.6 mm Hg, and MAP to 101.1 +/- 6.5 mm Hg", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8227469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Treating systolic hypertension in the very elderly with valsartan-hydrochlorothiazide vs. either monotherapy: ValVET primary results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21974759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "This 16-week trial investigated the efficacy and safety of single-pill valsartan/hydrochlorothiazide (HCTZ) vs. the individual components in patients 70years and older with systolic hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21974759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The article gives an overview of the risk factors for hypertension and the appropriate indication for using a fixed combination of telmisartan and hydrochlorothiazide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23767455", "endSection": "abstract" } ] }, { "body": "Are genes symmetrically distributed between leading and lagging DNA strand in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20417622", "http://www.ncbi.nlm.nih.gov/pubmed/25425232", "http://www.ncbi.nlm.nih.gov/pubmed/12217498", "http://www.ncbi.nlm.nih.gov/pubmed/14743977", "http://www.ncbi.nlm.nih.gov/pubmed/15942025", "http://www.ncbi.nlm.nih.gov/pubmed/11677621", "http://www.ncbi.nlm.nih.gov/pubmed/21350489", "http://www.ncbi.nlm.nih.gov/pubmed/15823418", "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "http://www.ncbi.nlm.nih.gov/pubmed/24273314", "http://www.ncbi.nlm.nih.gov/pubmed/22735706", "http://www.ncbi.nlm.nih.gov/pubmed/19221094", "http://www.ncbi.nlm.nih.gov/pubmed/23538833", "http://www.ncbi.nlm.nih.gov/pubmed/20600808" ], "ideal_answer": [ "In most bacteria, genes are preferentially encoded on the leading strand than on the lagging strand. This avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand. Head-on collisions are more deleterious than codirectional collisions, and may lead to replication fork arrest and genomic instability. Genes of some functional categories such as ribosome have higher preferences to be on the leading strands, while genes of other functional categories such as transcription factor have higher preferences on the lagging strands. Strand-biased gene distribution correlates with replication-associated purine asymmetry and the presence or absence of polC. Especially essential and highly transcribed genes and genes whose expression is important for fitness are more preferentially situated at the leading strand in bacteria." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006273" ], "type": "yesno", "id": "55425615ed966d112c000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Genomic DNA is used as the template for both replication and transcription, whose machineries may collide and result in mutagenesis, among other damages. Because head-on collisions are more deleterious than codirectional collisions, genes should be preferentially encoded on the leading strand to avoid head-on collisions, as is observed in most bacterial genomes examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273314", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 442, "text": "Most genes in bacteria are encoded on the leading strand of replication. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "The majority of bacterial genes are located on the leading strand", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735706", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 660, "text": "genes of some functional categories such as ribosome have higher preferences to be on the leading strands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735706", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 778, "text": "genes of some functional categories such as transcription factor have higher preferences on the lagging strands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735706", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 292, "text": "essential genes are more preferentially situated at the leading strand than at the lagging strand", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417622", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1121, "text": "remarkable strand-bias of the distribution of essential genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21350489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Replication-associated purine asymmetry may contribute to strand-biased gene distribution.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 207, "text": "strand-biased gene distribution (SGD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 522, "text": "SGD correlates not only with polC, but also with purine asymmetry (PAS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "In bacteria, most genes are on the leading strand of replication, a phenomenon attributed to collisions between the DNA and RNA polymerases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15942025", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 628, "text": "genes whose expression is important for fitness are selected to the leading strand because this reduces the duration of these interruptions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15942025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Among prokaryotic genomes, the distribution of genes on the leading and lagging strands of the replication fork is known to be biased. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 878, "text": "We show that the evidence they provided is invalid and that the existence of lagging strand encoded genes is explainable by a balance between deleterious mutations that bring genes from the leading to the lagging strand and purifying selection purging such mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273314", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 434, "text": "Based on those experimentally determined for 10 bacteria, we find that essential genes are more preferentially situated at the leading strand than at the lagging strand, for all the 10 genomes studied, confirming previous findings based on either smaller datasets or putatively assigned ones by homology search.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20417622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735706", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 261, "text": "Most genes in bacteria are encoded on the leading strand of replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538833", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 712, "text": "This paradox could be explained by assuming that the stronger mutation pressure and selection after inversion preferentially eliminate genes transferred from the leading to the lagging DNA strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11677621", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 515, "text": "We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11677621", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 260, "text": "Most genes in bacteria are encoded on the leading strand of replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735706", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 514, "text": "We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11677621", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 921, "text": "Using Monte Carlo methods, we have simulated, under experimentally determined directional mutation pressure, the divergence rate and the elimination rate of genes depending on their location in respect to the leading/lagging DNA strands in the asymmetric prokaryotic genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15823418", "endSection": "abstract" } ] }, { "body": "What hand deformities do patients with Apert syndrome present with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9145139", "http://www.ncbi.nlm.nih.gov/pubmed/1648464", "http://www.ncbi.nlm.nih.gov/pubmed/9719378", "http://www.ncbi.nlm.nih.gov/pubmed/12564817", "http://www.ncbi.nlm.nih.gov/pubmed/15162318", "http://www.ncbi.nlm.nih.gov/pubmed/211577", "http://www.ncbi.nlm.nih.gov/pubmed/9002682", "http://www.ncbi.nlm.nih.gov/pubmed/22196295", "http://www.ncbi.nlm.nih.gov/pubmed/11818821" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1469", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/100" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/100", "o": "http://www.dbpedia.org/resource/Apert_syndrome" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/100", "o": "Apert_syndrome" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1469", "o": "Apert syndrome, 101200" } ], "ideal_answer": [ "In patients with Apert syndrome, the hands demonstrate many disturbances of soft tissue and bony structures. These include a short thumb with radial clinodactyly, complex syndactyly with a bony fusion involving the index, long and ring fingers, symphalangism and simple syndactyly of the fourth web space. The soft tissue anomalies involve the intrinsic muscles, the extrinsic tendon insertions and the neurovascular bundles." ], "exact_answer": [ [ "complex syndactyly with bony fusion involving the index" ], [ "polydactyly" ], [ "short thumb with radial clinodactyly" ], [ "long and ring fingers" ], [ "symphalangism" ], [ "simple syndactyly of the fourth web space" ], [ "intrinsic muscle anomalies" ], [ "extrinsic tendon insertions" ], [ "neurovascular bundles" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000013", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.disease-ontology.org/api/metadata/DOID:12857", "http://www.disease-ontology.org/api/metadata/DOID:12960", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006226", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050823", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000168", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017880", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006228" ], "type": "list", "id": "52bf1cb303868f1b0600000b", "snippets": [ { "offsetInBeginSection": 360, "offsetInEndSection": 616, "text": "Five patients, ranging from Upton type 1 to type 3 Apert hand deformities, have had preoperative computed tomography angiography that delineated the vascular anatomy. This allowed planning and execution of a single-stage syndactyly release in all patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22196295", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 904, "text": "The protocol presented allows preoperative planning and single-stage operation for complete release of syndactyly in patients with Apert syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22196295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 426, "text": "In patients with Apert syndrome, the hands demonstrate many disturbances of soft tissue and bony structures. These include a short thumb with radial clinodactyly, complex syndactyly with a bony fusion involving the index, long and ring fingers, symphalangism and simple syndactyly of the fourth web space. The soft tissue anomalies involve the intrinsic muscles, the extrinsic tendon insertions and the neurovascular bundles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15162318", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 236, "text": "Two of the patients had Apert syndrome (syndromic craniosynostosis with symmetrical syndactyly) and two had polydactyly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12564817", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 796, "text": "The overall strategy involved early bilateral separation of syndactylous border digits at 1 year of age, followed by sequential unilateral middle syndactyly mass separation with thumb osteotomy and bone grafting as needed. In these 10 patients, a total of 53 web spaces were released, 49 of which involved osteotomies for complex syndactyly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11818821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Apert syndrome, characterised by craniosynostosis, craniofacial anomalies, and symmetrical syndactyly of the digits (cutaneous and bony fusion), has been associated with two canonical mutations in the FGFR2 gene (S252W, P253R) in the great majority of cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9719378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The Apert syndrome hand demonstrates many typical clinical features including syndactyly, symbrachyphalangism, and growth disturbances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9145139", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 446, "text": "In Apert syndrome, characterised by syndactyly of the hands and feet, recurrent mutations of a serine-proline dipeptide (either Ser252Trp or Pro253Arg) in the linker between the IgII and IgIII extracellular immunoglobulin-like domains, have been documented in more than 160 unrelated individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9002682", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 173, "text": "urgical correction of syndactyly of the Apert hand should begin by 6 months and be completed by 3 years of age. As much surgery as possible is carried out at each sitting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1648464", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1250, "text": "The syndactyly cases were more complicated than the average, among them 4 cases of Apert syndrome were noted. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/211577", "endSection": "abstract" } ] }, { "body": "Is c-myc subject to regulation by the circadian clock?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15817328", "http://www.ncbi.nlm.nih.gov/pubmed/20539819", "http://www.ncbi.nlm.nih.gov/pubmed/16827798", "http://www.ncbi.nlm.nih.gov/pubmed/20560708", "http://www.ncbi.nlm.nih.gov/pubmed/19010825", "http://www.ncbi.nlm.nih.gov/pubmed/19861541", "http://www.ncbi.nlm.nih.gov/pubmed/20576619", "http://www.ncbi.nlm.nih.gov/pubmed/24190490", "http://www.ncbi.nlm.nih.gov/pubmed/17660446", "http://www.ncbi.nlm.nih.gov/pubmed/16596306", "http://www.ncbi.nlm.nih.gov/pubmed/19957060" ], "ideal_answer": [ "Yes, the expression of c-myc is regulated by the circadian clock protein Per2." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016271", "http://www.uniprot.org/uniprot/MYC_CARAU", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032922", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001683", "http://www.uniprot.org/uniprot/MYC_GALVR", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007623", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042753", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042752", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071943", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097167", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016259", "http://www.uniprot.org/uniprot/MYC_ONCMY", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042754", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056950", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002940", "http://www.uniprot.org/uniprot/MYC_ASTRU", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057906" ], "type": "yesno", "id": "531616bdb166e2b806000003", "snippets": [ { "offsetInBeginSection": 611, "offsetInEndSection": 815, "text": "The current study encompasses the investigation of simultaneous expression of four circadian clock genes (Bmal1, Clock, Per1 and Per2) and three clock-controlled cell cycle genes (Myc, Cyclin D1 and Wee1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24190490", "endSection": "abstract" }, { "offsetInBeginSection": 1855, "offsetInEndSection": 2084, "text": "Our results suggest that aberrant expression of circadian clock genes can lead to aberrant expression of their downstream targets that are involved in cell proliferation and apoptosis and hence may result in manifestation of CLL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24190490", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 761, "text": "Loss of Bmal1 reduced the expression of per1, per2, per3, wee1 and p53. The expression of p21 and c-myc was also altered in certain cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20576619", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 534, "text": "In particular, the proto-oncogene c-Myc has been documented to be under circadian regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The circadian expression of c-MYC is modulated by the histone deacetylase inhibitor trichostatin A in synchronized murine neuroblastoma cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560708", "endSection": "title" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1579, "text": "Our results, using the murine neuroblastoma cell line N2A, show that Per1 and c-Myc steady-state mRNA levels oscillate with the same phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560708", "endSection": "abstract" }, { "offsetInBeginSection": 1872, "offsetInEndSection": 2160, "text": "These experiments demonstrate for the first time that a significant decrease in c-Myc transcript and protein levels can be achieved after a short TSA treatment applied only at specific circadian times. This is also followed by a reduction in the proliferation rate of the cell population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560708", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1166, "text": "Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20539819", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1439, "text": "Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20539819", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 586, "text": "The results showed that over-expression of Per2 induced not only cell cycle arrest at G2/M phase but also an increase in apoptosis, which was confirmed by characteristic morphological changes, FCM and evident DNA fragmentation. Further experiments confirmed both up-regulation of P53 and down-regulation of CylinB1and C-myc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19957060", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 706, "text": "On the other hand, while P53 was found to be down-regulated. CylinB1 and C-myc were up-regulated. after Per2 knockdown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19957060", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1154, "text": "We also show that BMAL1 epigenetic inactivation impairs the characteristic circadian clock expression pattern of genes such as C-MYC, catalase, and p300 in association with a loss of BMAL1 occupancy in their respective promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19861541", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 382, "text": "Per2 mutant (Per2(m/m)) mice show an increase in lymphomas and deregulated expression of cyclin D and c-Myc genes that are key to proliferation control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19010825", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 401, "text": "The expression of cell cycle genes such as Wee1, Cyclins, and c-Myc are under circadian control and could be directly under the regulation of the circadian transcriptional complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17660446", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 635, "text": "Overexpressed mPER2 also altered the expression of apoptosis-related genes. The mRNA and protein levels of c-Myc, Bcl-X(L) and Bcl-2 were downregulated,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16827798", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 967, "text": "Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha is deregulated in mPer2 mutant mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596306", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 967, "text": "The temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15817328", "endSection": "abstract" } ] }, { "body": "What disease is Velcade (bortezomib) mainly used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15626743", "http://www.ncbi.nlm.nih.gov/pubmed/21751810", "http://www.ncbi.nlm.nih.gov/pubmed/22381702", "http://www.ncbi.nlm.nih.gov/pubmed/23176720", "http://www.ncbi.nlm.nih.gov/pubmed/20079210", "http://www.ncbi.nlm.nih.gov/pubmed/21223249", "http://www.ncbi.nlm.nih.gov/pubmed/15985470", "http://www.ncbi.nlm.nih.gov/pubmed/22353937", "http://www.ncbi.nlm.nih.gov/pubmed/21634429", "http://www.ncbi.nlm.nih.gov/pubmed/20685499", "http://www.ncbi.nlm.nih.gov/pubmed/19190249", "http://www.ncbi.nlm.nih.gov/pubmed/16470606", "http://www.ncbi.nlm.nih.gov/pubmed/18410447", "http://www.ncbi.nlm.nih.gov/pubmed/22028144", "http://www.ncbi.nlm.nih.gov/pubmed/18381602", "http://www.ncbi.nlm.nih.gov/pubmed/21501555", "http://www.ncbi.nlm.nih.gov/pubmed/17133426", "http://www.ncbi.nlm.nih.gov/pubmed/21839906", "http://www.ncbi.nlm.nih.gov/pubmed/22699304", "http://www.ncbi.nlm.nih.gov/pubmed/22189222", "http://www.ncbi.nlm.nih.gov/pubmed/18327587", "http://www.ncbi.nlm.nih.gov/pubmed/22087865" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A15661541", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1174739", "o": "http://linkedlifedata.com/resource/umls/label/A4368130" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A4368130", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A7589426", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10483519", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A4361967", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A7827139", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "Velcade (bortezomid), a proteasome inhibitor drug indicated for multiple myeloma (MM) treatment. Velcade is also approved for the treatment of patients with mantle cell lymphoma." ], "exact_answer": [ "multiple myeloma" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2001025", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2001023", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0017144", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008144", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042737", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2001039", "http://www.disease-ontology.org/api/metadata/DOID:9974", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2001040", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042493", "http://www.biosemantics.org/jochem#4241338" ], "type": "factoid", "id": "51631154298dcd4e5100004e", "snippets": [ { "offsetInBeginSection": 5, "offsetInEndSection": 40, "text": "patients with multiple myeloma (MM)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176720", "endSection": "sections.0" }, { "offsetInBeginSection": 166, "offsetInEndSection": 242, "text": "bortezomib, and lenalidomide have shown improved outcomes in these patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176720", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 212, "text": "Bortezomib, a proteasome inhibitor drug very effective against multiple myeloma, may induce the so-called bortezomib-induced peripheral neuropathy (BIPN), hardly manageable with common analgesic drugs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699304", "endSection": "sections.0" }, { "offsetInBeginSection": 714, "offsetInEndSection": 800, "text": "bortezomib have emerged as effective treatment in patients with multiple myeloma (MM).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22381702", "endSection": "sections.0" }, { "offsetInBeginSection": 275, "offsetInEndSection": 481, "text": "the use of thalidomide to treat multiple myeloma, and describe problems arising in the Thaled\u00ae outpatient department. METHODS: Multiple myeloma patients treated with thalidomide at Hitachi General Hospital.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22189222", "endSection": "sections.0" }, { "offsetInBeginSection": 1363, "offsetInEndSection": 1676, "text": "Thalidomide showed some success in treating multiple myeloma either after auto-PBSCT or following treatment with bortezomib. In the case demonstrating hematotoxicity Grade 3 (in addition to neutropenia), grave complications could have very easily developed, thus underscoring the importance of careful monitoring.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22189222", "endSection": "sections.0" }, { "offsetInBeginSection": 525, "offsetInEndSection": 731, "text": "Patients aged \u226518 years with relapsed or refractory multiple myeloma or non-Hodgkin's lymphoma received intravenous bortezomib 1.3\u2009mg/m2, administered on days 1, 4, 8 and 11 of a 21-day cycle, for 3 cycles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22087865", "endSection": "sections.0" }, { "offsetInBeginSection": 2100, "offsetInEndSection": 2414, "text": "In patients with multiple myeloma or non-Hodgkin's lymphoma, co-administration of rifampicin decreased the exposure to bortezomib but did not affect the proteasome inhibition or safety profiles; co-administration of dexamethasone did not affect the exposure to bortezomib, proteasome inhibition or safety profiles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22087865", "endSection": "sections.0" }, { "offsetInBeginSection": 615, "offsetInEndSection": 818, "text": "we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, lenalidomide and/or bortezomib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028144", "endSection": "sections.0" }, { "offsetInBeginSection": 96, "offsetInEndSection": 245, "text": "Bortezomib, indicated for multiple myeloma (MM) treatment, is available in 3.5-mg vials, a quantity higher than the average dose commonly prescribed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839906", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21634429", "endSection": "sections.0" }, { "offsetInBeginSection": 26, "offsetInEndSection": 257, "text": "efficacy and safety of bortezomib (BOR) for treatment of multiple myeloma in comparison with thalidomide (THAL) by reference to adverse events, and searched for laboratory markers that could be used for prognostication of patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501555", "endSection": "sections.0" }, { "offsetInBeginSection": 607, "offsetInEndSection": 907, "text": "BOR showed a higher rate of effectiveness than THAL for refractory multiple myeloma, and its effects were rapid. BOR treatment prolonged the survival time of THAL-resistant patients. The efficacy of BOR was unrelated to patient age, the number of previous therapeutic regimens, or the disease period.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501555", "endSection": "sections.0" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1547, "text": "It is suggested that BOR has therapeutic efficacy for multiple myeloma as a first-line medical treatment and/or for patients with THAL resistance, and can improve prognosis and survival. Since serum ALP elevation was observed in many patients for whom BOR was effective, this may be a predictor of BOR efficacy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501555", "endSection": "sections.0" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1404, "text": "Bortezomib-treated MM patients whose tumours had high baseline expression of genes suppressed by LCQ195 had significantly shorter progression-free and overall survival than those with low levels of these transcripts in their MM cells. These observations provide insight into the biological relevance of multi-targeted CDK inhibition in MM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21223249", "endSection": "sections.0" }, { "offsetInBeginSection": 57, "offsetInEndSection": 294, "text": "bortezomib is the only effective agent in the treatment of plasma cell leukemia (PCL), a type of plasma cell dyscrasia characterized by poor prognosis despite conventional chemotherapy including autologous and allogeneic transplantation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20685499", "endSection": "sections.0" }, { "offsetInBeginSection": 2518, "offsetInEndSection": 2655, "text": "These 3 patients with primary or secondary PCL who received a bortezomib-based regimen as rescue medication did not respond to treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20685499", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 162, "text": "To evaluate the effects and safety of the regimen of bortezomib combined with dexamethasone (VD) in the treatment of primary systemic (AL) amyloidosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20079210", "endSection": "sections.0" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1025, "text": "VD regimen might be an efficient, rapid effective and safe regimen in the treatment of AL amyloidosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20079210", "endSection": "sections.0" }, { "offsetInBeginSection": 240, "offsetInEndSection": 496, "text": "Bortezomib (BZM) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19190249", "endSection": "sections.0" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1404, "text": "Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19190249", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Relapsed/refractory myeloma has a poor outcome because of multi-drug resistance, patient low-performance status and toxicity of conventional chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410447", "endSection": "sections.0" }, { "offsetInBeginSection": 273, "offsetInEndSection": 607, "text": "Bortezomib, by inhibiting proteasome function, may enhance chemosensitivity to other drugs and overcome drug-resistance. Notably, doxorubicin and bortezomib may reciprocally increase their efficacy. Thus, to improve outcome whilst minimizing therapy-related toxicity, liposomal doxorubicin was added to a bortezomib-based combination.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410447", "endSection": "sections.0" }, { "offsetInBeginSection": 371, "offsetInEndSection": 703, "text": "the growth inhibitory and pro-apoptotic effects of the proteasome inhibitor bortezomib in combination with anti-EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR-expressing human cancer cell lines. Bortezomib determined dose-dependent growth inhibition in a nine cancer cell line panel (IC(50) values, range 6-42 nM).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18381602", "endSection": "sections.0" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1727, "text": "overexpression of a constitutively active P-Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18381602", "endSection": "sections.0" }, { "offsetInBeginSection": 1353, "offsetInEndSection": 1431, "text": "Among 19 patients with breast cancer, four had evidence of a clinical benefit.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18327587", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 265, "text": "Pre-clinical studies combining the proteasome inhibitor bortezomib with anthracyclines have shown enhanced anti-tumor activity. We conducted a phase I trial of bortezomib and pegylated liposomal doxorubicin (PLD) in patients with refractory solid tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18327587", "endSection": "sections.0" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1722, "text": "A regimen of bortezomib, 1.3 mg/m(2) on days 1, 4, 8, and 11 with PLD, 30 mg/m(2), on day 4 of a 21-day cycle, was safe in this study, and merits further investigation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18327587", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Bortezomib, a proteasome inhibitor, has been used for patients with refractory and relapsed multiple myeloma, lymphoma and leukemia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17133426", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 168, "text": "Bortezomib, a first-in-class proteasome inhibitor, has shown clinical activity in relapsed, refractory multiple myeloma in a pivotal Phase II trial, SUMMIT.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16470606", "endSection": "sections.0" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1651, "text": "treatment with bortezomib results in meaningful long-term benefit for patients with relapsed and refractory myeloma.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16470606", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 205, "text": "The proteasome inhibitor bortezomib (BTZ), used in antineoplastic chemotherapy, must be diluted in NaCl 0.9% for injection and stored for no more than 3 hours in a syringe or 8 hours in a vial.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15985470", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on days 1, 4, 8, and 11 from 0.90 to 1.50 mg/m2 and PegLD on day 4 at 30 mg/m2 to 42 patients with advanced hematologic malignancies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15626743", "endSection": "sections.0" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1471, "text": "Antitumor activity was seen against multiple myeloma, with 8 of 22 evaluable patients having a complete response (CR) or near-CR, including several with anthracycline-refractory disease, and another 8 having partial responses (PRs). One patient with relapsed/refractory T-cell non-Hodgkin lymphoma (NHL) achieved a CR, whereas 2 patients each with acute myeloid leukemia and B-cell NHL had PRs. Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15626743", "endSection": "sections.0" }, { "offsetInBeginSection": 694, "offsetInEndSection": 801, "text": "These patients were treated with bortezomib variously combined with other drugs outside of clinical trials.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20685499", "endSection": "sections.0" } ] }, { "body": "Which genes are thought to be involved in medulloblastoma development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21597995", "http://www.ncbi.nlm.nih.gov/pubmed/14688019", "http://www.ncbi.nlm.nih.gov/pubmed/12384556", "http://www.ncbi.nlm.nih.gov/pubmed/10738305", "http://www.ncbi.nlm.nih.gov/pubmed/19048113", "http://www.ncbi.nlm.nih.gov/pubmed/15705863", "http://www.ncbi.nlm.nih.gov/pubmed/20717685", "http://www.ncbi.nlm.nih.gov/pubmed/24252690" ], "ideal_answer": [ "Medulloblastomas are the most frequent malignant brain tumors affecting children. Disease development has been suggested to be associated with a significant number of genes, such as PTCH1, SUFU, PTEN, CREBBP, PTEN, MYT1L, NFIA, NFIB, TEAD1, TGIF2, IGF2, PCDH10, BMI1, MYC, OTX2, RASSF1A, HIC1, and CASP8." ], "exact_answer": [ [ "PTCH1" ], [ "SUFU" ], [ "PTEN" ], [ "CREBBP" ], [ "PTEN" ], [ "MYT1L" ], [ "NFIA" ], [ "NFIB" ], [ "TEAD1" ], [ "TGIF2" ], [ "IGF2" ], [ "PCDH10" ], [ "BMI1" ], [ "MYC" ], [ "OTX2" ], [ "RASSF1A" ], [ "HIC1" ], [ "CASP8" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3858" ], "type": "list", "id": "5539029cbc4f83e828000012", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 436, "text": "Medulloblastomas, the most frequent malignant brain tumours affecting children, comprise at least 4 distinct clinicogenetic subgroups. Aberrant sonic hedgehog (SHH) signalling is observed in approximately 25% of tumours and defines one subgroup. Although alterations in SHH pathway genes (e.g. PTCH1, SUFU) are observed in many of these tumours, high throughput genomic analyses have identified few other recurring mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252690", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 1156, "text": "Mutagenesis significantly increased medulloblastoma frequency and identified 17 candidate cancer genes, including orthologs of genes somatically mutated (PTEN, CREBBP) or associated with poor outcome (PTEN, MYT1L) in the human disease. Strikingly, these candidate genes were enriched for transcription factors (p=2x10-5), the majority of which (6/7; Crebbp, Myt1L, Nfia, Nfib, Tead1 and Tgif2) were linked within a single regulatory network enriched for genes associated with a differentiated neuronal phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252690", "endSection": "abstract" }, { "offsetInBeginSection": 1363, "offsetInEndSection": 1497, "text": "Igf2, previously implicated in medulloblastoma, was the most differentially expressed gene in murine tumours with network perturbation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "PCDH10 is a candidate tumour suppressor gene in medulloblastoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21597995", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 145, "text": "The aim of this study was to investigate the genetic and epigenetic mechanisms contributing to PCDH10 down-regulation in medulloblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21597995", "endSection": "abstract" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1174, "text": "We report a very focal homozygous deletion on chromosome 4q28.3 harbouring the PCDH10 gene. We demonstrate that PCDH10 transcription is down-regulated in 19/26 (73%) of medulloblastomas suggesting that other mechanisms also could be involved in gene repression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21597995", "endSection": "abstract" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1732, "text": "Our findings suggest that genetic and epigenetic deregulation of PCDH10 occurs in a significant portion of medulloblastoma patients. Failure to express PCDH10 may result in loss of inhibition of cell migration, thereby contributing to medulloblastoma progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21597995", "endSection": "abstract" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1078, "text": "We found that the higher expression levels of BMI1 and PCGF2 genes were associated with significantly decreased patient survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20717685", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1384, "text": "Our analysis showed correlation between BMI1 and PCGF2 gene's expression and survival in children with medulloblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20717685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Bmi1 is required for Hedgehog pathway-driven medulloblastoma expansion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19048113", "endSection": "title" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1773, "text": "These data provide the first demonstration that Bmi1 is required for spontaneous de novo development of a solid tumor arising in the brain, suggest a crucial role for Bmi1-dependent, nestin-expressing progenitor cells in medulloblastoma expansion, and implicate Bmi1 as a key factor required for Hh pathway-driven tumorigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19048113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Genomic amplification of orthodenticle homologue 2 in medulloblastomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15705863", "endSection": "title" }, { "offsetInBeginSection": 459, "offsetInEndSection": 900, "text": "Genomic alterations normally associated with medulloblastomas, including MYC amplification and isochromosome 17q, were easily detected. Surprisingly, analysis of only five genomes revealed novel amplicons on chromosome 14q, one of which contained the orthodenticle homologue 2 (OTX2) homeobox gene. DNA copy number analysis showed that OTX2 had undergone genomic amplification in 2 of 11 medulloblastoma cell lines and 8 of 42 primary tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15705863", "endSection": "abstract" }, { "offsetInBeginSection": 1300, "offsetInEndSection": 1487, "text": "Serial analysis of gene expression of 240 different human tumors or normal tissues revealed that 96% of all 783 OTX2 transcripts sequenced were in medulloblastomas or embryonic stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15705863", "endSection": "abstract" }, { "offsetInBeginSection": 1489, "offsetInEndSection": 1691, "text": "OTX2 functions to specify the fate of neuroectoderm in various regions of the developing brain. This developmental role is consistent with the evidence suggesting that OTX2 is a medulloblastoma oncogene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15705863", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 793, "text": "Extensive hypermethylation of RASSF1A was detected frequently in medulloblastomas but not in the normal cerebellum (41/44 primary tumours versus 0/5 normal cerebella)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14688019", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 984, "text": "In contrast, complete methylation of HIC1 and CASP8 in a subset of primary tumours (17/44 and 14/39) occurred against a consistent background of partial methylation in the normal cerebellum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14688019", "endSection": "abstract" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1115, "text": "These data therefore indicate that extensive methylation of RASSF1A, HIC1 and CASP8 are tumour-specific events in medulloblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14688019", "endSection": "abstract" }, { "offsetInBeginSection": 1885, "offsetInEndSection": 2061, "text": "We conclude that epigenetic TSG inactivation is a significant feature of medulloblastoma, and identify RASSF1A, HIC1 and CASP8 as potentially critical genes in its pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14688019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Biallelic epigenetic inactivation of the RASSF1A tumor suppressor gene in medulloblastoma development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12384556", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 370, "text": "Seventy-nine % (27 of 34) of primary tumors and 100% (8 of 8) of medulloblastoma cell lines displayed extensive tumor-specific DNA hypermethylation across the RASSF1A promoter-associated CpG island", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12384556", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 616, "text": "Hypermethylation was associated with epigenetic silencing of RASSF1A transcription in medulloblastoma cell lines, and RASSF1A expression in these lines was restored after treatment with the DNA-methyltransferase inhibitor 5-aza-2'-deoxycytidine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12384556", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1023, "text": "Epigenetic inactivation by biallelic hypermethylation therefore represents the primary mechanism of RASSF1A gene inactivation in medulloblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12384556", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1237, "text": "RASSF1A hypermethylation is a frequent event in medulloblastoma tumorigenesis detectable in adult (5 of 7) and pediatric patients (22 of 27) and in all histological variants and age and sex groupings", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12384556", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 330, "text": "Medulloblastoma, a brain tumor, develops in about 3% of NBCCS patients, and mutations in PTCH have also been described in a subset of sporadic medulloblastomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10738305", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 652, "text": "Recently, a transgenic mouse hemizygous for the Ptch gene was generated by homologous recombination. Medulloblastomas were found in about 19% of these mice within the first 25 weeks after birth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10738305", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1714, "text": "We also examined the mRNA expression levels for the remaining Ptch allele, as well as for Gli1, a gene known to be transcriptionally activated by Ptch inactivation. Blot analysis of RNA from the 13 tumors shows that Ptch mRNA of appropriate size is expressed in all tumors at varying levels. Expression of Gli1 was increased in tumors compared to normal cerebellum. These results suggest that deletion of one copy of Ptch may be sufficient to promote medulloblastoma development in mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10738305", "endSection": "abstract" } ] }, { "body": "What is the prevalence of short QT syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17679619", "http://www.ncbi.nlm.nih.gov/pubmed/18070308", "http://www.ncbi.nlm.nih.gov/pubmed/18543308", "http://www.ncbi.nlm.nih.gov/pubmed/19303371", "http://www.ncbi.nlm.nih.gov/pubmed/21855519" ], "ideal_answer": [ "The prevalence of short QT syndrome is low and varies between 0.01% and 0.1%" ], "exact_answer": [ "0.01% -0.1%" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015995" ], "type": "factoid", "id": "52fb78572059c6d71c000067", "snippets": [ { "offsetInBeginSection": 384, "offsetInEndSection": 714, "text": "We chose patients with a short Bazett QTc interval from a database consisting of 114,334 patients to determine the clinical characteristics and prognostic value of a short QT interval. RESULTS: A total of 427 patients (mean age 43.4 \u00b1 22.4 years) had a short QT interval with about a 1.2 times higher male predominance (234 men). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21855519", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1347, "text": "Among 5,511 males, 69 subjects (1.25%) exhibited QTc < 354 msec(1/2) (2 standard deviations [SDs] below the mean in males), and among 5,473 females, 89 subjects (1.63%) exhibited QTc < 364 msec(1/2) (2 SDs below the mean in females). Only 3 subjects (0.03% in all subjects and 0.05% in males) exhibited QTc < 300 msec(1/2), however, none had clinical symptoms of short QT syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18543308", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 640, "text": "Of the 19,153 subjects, two met the criteria of short QT interval and allowed for prevalence and incidence estimates for short QT interval as 0.01% and 0.39/100,000 person-years, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18070308", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1065, "text": "The prevalence of QT interval <320 ms based on QTc, QTfc, and QTnc was 0.10%, 0.08%, and 0.06%, and the prevalence of QT interval <340 ms was 0.4%, 0.3%, and 0.3%, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17679619", "endSection": "abstract" } ] }, { "body": "Which sports have a risk for commotio cordis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10392228", "http://www.ncbi.nlm.nih.gov/pubmed/7609749", "http://www.ncbi.nlm.nih.gov/pubmed/19706581", "http://www.ncbi.nlm.nih.gov/pubmed/23015869", "http://www.ncbi.nlm.nih.gov/pubmed/11048776", "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "http://www.ncbi.nlm.nih.gov/pubmed/10338239", "http://www.ncbi.nlm.nih.gov/pubmed/17350382", "http://www.ncbi.nlm.nih.gov/pubmed/11208236", "http://www.ncbi.nlm.nih.gov/pubmed/21763255", "http://www.ncbi.nlm.nih.gov/pubmed/20086611", "http://www.ncbi.nlm.nih.gov/pubmed/11130483", "http://www.ncbi.nlm.nih.gov/pubmed/22869311", "http://www.ncbi.nlm.nih.gov/pubmed/15262641" ], "ideal_answer": [ "Participation in sports such as baseball, football, soccer, cricket, hockey and lacrosse has a risk for commotio cordis." ], "exact_answer": [ [ "baseball" ], [ "football" ], [ "soccer" ], [ "cricket" ], [ "hockey" ], [ "lacrosse" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056104" ], "type": "list", "id": "5300aad02059c6d71c000080", "snippets": [ { "offsetInBeginSection": 309, "offsetInEndSection": 425, "text": "This study sought to characterize the demographics of commotio cordis globally in comparison to the U.S. experience.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21763255", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1213, "text": "Not unexpectedly, the groups differed with baseball/softball and football predominant in the United States (55% of events) and soccer, cricket, and hockey most common internationally (47% of events). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21763255", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 393, "text": "The authors reviewed 41 incidents of baseball injuries reported to the National Center for Catastrophic Sports Injury Research from 1982 until 2002.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262641", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 867, "text": "Catastrophic injuries included 23 severe head injuries, 8 cervical injuries, 3 cases of commotio cordis, and 2 cases each of a collapsed trachea and facial fractures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262641", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 858, "text": "Commotio cordis events occurred most commonly during organized sporting events (79 [62%]), such as baseball, but 49 (38%) occurred as part of daily routine and recreational activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1366, "text": "Twenty-two (28%) participants were wearing commercially available chest barriers, including 7 in whom the projectile made direct contact with protective padding (baseball catchers and lacrosse/hockey goalies), and 2 in whom the projectile was a baseball specifically designed to reduce risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 219, "text": "In a recent study of fatal chest impacts by baseballs, 28% of the children were wearing a chest protector. This study evaluates the effectiveness of chest protectors in reducing the risk of commotio cordis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11130483", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 517, "text": "It has been described after blows to the chest from baseballs, softballs, hockey pucks, and other objects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11208236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Commotio cordis due to blunt trauma to the precordium is a rare cause of death in young athletes, occurring less frequently than all of the other athletics-related deaths. Several measures, such as the use of safety baseballs and the use of chest protectors, can help protect young athletes from commotio cordis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10392228", "endSection": "abstract" } ] }, { "body": "is there an increase in ultrasound comets after intense exercise?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19997032", "http://www.ncbi.nlm.nih.gov/pubmed/23453728", "http://www.ncbi.nlm.nih.gov/pubmed/21873499", "http://www.ncbi.nlm.nih.gov/pubmed/21535186", "http://www.ncbi.nlm.nih.gov/pubmed/16581487", "http://www.ncbi.nlm.nih.gov/pubmed/9372688", "http://www.ncbi.nlm.nih.gov/pubmed/18926391", "http://www.ncbi.nlm.nih.gov/pubmed/23871437", "http://www.ncbi.nlm.nih.gov/pubmed/21766015", "http://www.ncbi.nlm.nih.gov/pubmed/15135701", "http://www.ncbi.nlm.nih.gov/pubmed/20972574", "http://www.ncbi.nlm.nih.gov/pubmed/20188217", "http://www.ncbi.nlm.nih.gov/pubmed/16500505" ], "ideal_answer": [ "Strenuous exercise and exercise perfomed in extreme conditions provoke increase in interstitial pulmonary water content as shown by the increased number of ultrasuond comets" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020552", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014463", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016477", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ], "type": "yesno", "id": "531c380db166e2b80600003f", "snippets": [ { "offsetInBeginSection": 1241, "offsetInEndSection": 1458, "text": "Healthy athletes developed subclinical increase in pulmonary water content immediately after an Ironman race at sea level, as shown by the increased number of ULCs related to cardiac changes occurring during exercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21873499", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1830, "text": "Increased EVLW is associated with estimated PCWP and indices of left ventricular systolic and diastolic dysfunction. The additional exercise-induced increase of PCWP, the worsening of left ventricular diastolic function, and extensive wall-motion abnormalities correlate with variations of EVLW.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16581487", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 882, "text": " Among them chest ultrasonography can detect and quantify the extravascular lung water, creating \"comet-tail\" ultrasound artefacts (ULCs) from water-thickened pulmonary interlobular septa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21766015", "endSection": "abstract" }, { "offsetInBeginSection": 1757, "offsetInEndSection": 1984, "text": " In top-level breath-hold divers, chest sonography frequently reveals an increased number of ULCs after immersion, indicating a relatively high prevalence of (often subclinical) reversible extravascular lung water accumulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18926391", "endSection": "abstract" } ] }, { "body": "Describe Hot water reflex epilepsy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15297690", "http://www.ncbi.nlm.nih.gov/pubmed/24691301", "http://www.ncbi.nlm.nih.gov/pubmed/18367432", "http://www.ncbi.nlm.nih.gov/pubmed/19266219", "http://www.ncbi.nlm.nih.gov/pubmed/3338422", "http://www.ncbi.nlm.nih.gov/pubmed/10695897", "http://www.ncbi.nlm.nih.gov/pubmed/21808513", "http://www.ncbi.nlm.nih.gov/pubmed/20220445", "http://www.ncbi.nlm.nih.gov/pubmed/18160259", "http://www.ncbi.nlm.nih.gov/pubmed/3284751", "http://www.ncbi.nlm.nih.gov/pubmed/19597845", "http://www.ncbi.nlm.nih.gov/pubmed/24691294", "http://www.ncbi.nlm.nih.gov/pubmed/10429817", "http://www.ncbi.nlm.nih.gov/pubmed/24929679", "http://www.ncbi.nlm.nih.gov/pubmed/24766826", "http://www.ncbi.nlm.nih.gov/pubmed/21932090", "http://www.ncbi.nlm.nih.gov/pubmed/25506178" ], "ideal_answer": [ "Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. HWE can be symptomatic of focal cortical malformation, and few cases were reported. Intermittent clobazam prophylaxis prior to head water bath might be a preferred mode of treatment of pure HWE." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004827" ], "type": "summary", "id": "56c1f031ef6e39474100004e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "In this review we assess our currently available knowledge about reflex seizures with special emphasis on the difference between \"generalized\" reflex seizures induced by visual stimuli, thinking, praxis and language tasks, and \"focal\" seizures induced by startle, eating, music, hot water, somatosensory stimuli and orgasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24766826", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1158, "text": "CONCLUSIONS: Intermittent clobazam prophylaxis prior to head water bath might be a preferred mode of treatment of pure HWE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24929679", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 430, "text": "Different types of reflex epilepsy such as eating, startle myoclonus, and hot water epilepsy were included in the study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24691294", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1393, "text": "Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24691294", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 398, "text": "Hot water epilepsy is rarely described in European countries, where bathing epilepsy in younger children is more common and often confused with this type of epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24691301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "We studied the anatomical correlates of reflex hot water epilepsy (HWE) using multimodality investigations viz. magnetic resonance imaging (MRI), electroencephalography (EEG), and single photon emission computed tomography (SPECT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506178", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 929, "text": "The clinical and SPECT studies suggested temporal lobe as the seizure onset zone in some of the patients with HWE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. HWE can be symptomatic of focal cortical malformation, and few cases were reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Hot water epilepsy is a reflex or sensory epilepsy in which seizures are triggered by the stimulus of bathing in hot water", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19597845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932090", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1392, "text": "Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24691294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Hot water epilepsy: A rare form of reflex epilepsy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21808513", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Hot water epilepsy is a form of reflex epilepsy in childhood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21808513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "We studied the anatomical correlates of reflex hot water epilepsy (HWE) using multimodality investigations viz. magnetic resonance imaging (MRI), electroencephalography (EEG), and single photon emission computed tomography (SPECT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Hot water epilepsy is a reflex or sensory epilepsy in which seizures are triggered by the stimulus of bathing in hot water. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19597845", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 592, "text": "The diagnosis of hot water epilepsy was supported by an ictal EEG. Hot water epilepsy, also known as bathing epilepsy or water-immersion epilepsy is, in the Caucasian population, a rare form of benign epilepsy, where seizures are provoked by immersion in a hot or even just a warm bath. This is the first comprehensive video publication of a seizure provoked by water-immersion in a Caucasian child. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18367432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Hot water epilepsy (HWE) is a form of reflex or sensory epilepsy wherein seizures are precipitated by an unusual stimulus, the contact of hot water over the head and body. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19266219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Hot water epilepsy (HWE) is a rare form of reflex epilepsy caused by bathing with hot water. In this paper, we describe three cases with hot water epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15297690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": ""Hot water epilepsy" (HWE), precipitated by a bath or shower in hot water, has been described infrequently in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3338422", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 399, "text": "A video-EEG recording was taken while hot water was poured onto his chest. Hot water epilepsy is rarely described in European countries, where bathing epilepsy in younger children is more common and often confused with this type of epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24691301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Hot water epilepsy (HWE) or bathing epilepsy is one of the reflex epilepsies induced by hot water pouring over the head,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20220445", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 643, "text": "These two patients are the youngest reported cases of reflex hot water seizures, and the only reported cases in which reflex hot water seizures subsequently manifested episodes of alternating hemiplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18160259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Hot water epilepsy is a reflex epilepsy. Seizures are provoked by hot water, and result from the association of both cutaneous and heat stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10695897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Hot water epilepsy belongs to the group of reflex epilepsies. Seizures are provoked by hot water, due to the association of both cutaneous and heat stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10429817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "A patient with reflex epilepsy is described, in whom seizures were induced by bathing in hot water.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3284751", "endSection": "abstract" } ] }, { "body": "What are the breath test biomarkers of pulmonary tuberculosis", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22366996", "http://www.ncbi.nlm.nih.gov/pubmed/20805989", "http://www.ncbi.nlm.nih.gov/pubmed/21219679", "http://www.ncbi.nlm.nih.gov/pubmed/22771606", "http://www.ncbi.nlm.nih.gov/pubmed/16635588", "http://www.ncbi.nlm.nih.gov/pubmed/16194024", "http://www.ncbi.nlm.nih.gov/pubmed/23737604", "http://www.ncbi.nlm.nih.gov/pubmed/19481976", "http://www.ncbi.nlm.nih.gov/pubmed/20189456", "http://www.ncbi.nlm.nih.gov/pubmed/23499413", "http://www.ncbi.nlm.nih.gov/pubmed/22647661" ], "ideal_answer": [ "Nitric oxide, urea, volatile organic compounds, hydrogen peroxide and end products of lipid peroxidation are the breath test biomarkers of pulmonary tuberculosis." ], "exact_answer": [ [ "nitric oxide" ], [ "urea" ], [ "volatile organic compounds" ], [ "hydrogen peroxide" ], [ "end products of lipid peroxidation" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2957", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001944", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014397" ], "type": "list", "id": "55181d1e6487737b43000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "BACKGROUND: Nitric oxide (NO), a key macrophage antimycobacterial mediator that ameliorates immunopathology, is measurable in exhaled breath in individuals with pulmonary tuberculosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23737604", "endSection": "abstract" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1677, "text": "CONCLUSIONS: Among patients with pulmonary tuberculosis, impaired pulmonary NO bioavailability is associated with more-severe disease and delayed mycobacterial clearance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23737604", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1331, "text": "Four KI windows corresponded with KI values of VOCs previously identified as biomarkers of pulmonary TB and metabolic products of M. tuberculosis, principally derivatives of naphthalene, benzene and alkanes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Measurement of exhaled nitric oxide as a potential screening tool for pulmonary tuberculosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219679", "endSection": "title" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1370, "text": "CONCLUSION: While eNO measurement has limited value in the direct diagnosis of pulmonary TB, it may be worth developing and evaluating as a cost-effective replacement of chest X-ray in screening algorithms of pulmonary TB where X-ray is not available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805989", "endSection": "title" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1577, "text": "CONCLUSIONS/SIGNIFICANCE: Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805989", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 1009, "text": "RESULTS: Breath VOCs contained apparent biomarkers of active pulmonary tuberculosis comprising oxidative stress products (alkanes and alkane derivatives) and volatile metabolites of M. tuberculosis (cyclohexane and benzene derivatives).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20189456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Pulmonary tuberculosis may alter volatile organic compounds (VOCs) in breath because Mycobacteria and oxidative stress resulting from Mycobacterial infection both generate distinctive VOCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16635588", "endSection": "abstract" }, { "offsetInBeginSection": 1705, "offsetInEndSection": 2095, "text": "We conclude that volatile biomarkers in breath were sensitive and specific for pulmonary tuberculosis: the breath test distinguished between \"sick versus well\" i.e. between normal controls and patients hospitalized for suspicion of pulmonary tuberculosis, and between infected versus non-infected patients i.e. between those whose sputum cultures were positive or negative for Mycobacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16635588", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 782, "text": "RESULTS: The concentrations of H202 and TBARs (1022.96+/-186.02 nM and 4.22+/-0. 80 microM, respectively) were significantly higher in patients with tuberculosis as compared with the controls (398.15+/-37.10 nM and 0.48+/-0.17 microM, respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16194024", "endSection": "abstract" }, { "offsetInBeginSection": 1689, "offsetInEndSection": 1852, "text": "We conclude that volatile biomarkers in breath were sensitive and specific for pulmonary tuberculosis: the breath test distinguished between \"sick versus well\" i.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16635588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Volatile organic compounds (VOCs) in breath may contain biomarkers of active pulmonary tuberculosis derived from the infectious organism (metabolites of Mycobacterium tuberculosis) and from the infected host (products of oxidative stress).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20189456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Volatile biomarkers of pulmonary tuberculosis in the breath.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16635588", "endSection": "title" }, { "offsetInBeginSection": 745, "offsetInEndSection": 920, "text": "Breath VOCs contained apparent biomarkers of active pulmonary tuberculosis comprising oxidative stress products (alkanes and alkane derivatives) and volatile metabolites of M.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20189456", "endSection": "abstract" }, { "offsetInBeginSection": 1730, "offsetInEndSection": 1862, "text": "CONCLUSIONS: A six-minute point-of-care breath test for volatile biomarkers accurately identified subjects with active pulmonary TB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "BACKGROUND: Volatile organic compounds (VOCs) in breath may contain biomarkers of active pulmonary tuberculosis derived from the infectious organism (metabolites of Mycobacterium tuberculosis) and from the infected host (products of oxidative stress).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20189456", "endSection": "abstract" }, { "offsetInBeginSection": 1707, "offsetInEndSection": 1868, "text": "We conclude that volatile biomarkers in breath were sensitive and specific for pulmonary tuberculosis: the breath test distinguished between \"sick versus well\" i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16635588", "endSection": "abstract" }, { "offsetInBeginSection": 1705, "offsetInEndSection": 1868, "text": "We conclude that volatile biomarkers in breath were sensitive and specific for pulmonary tuberculosis: the breath test distinguished between \"sick versus well\" i.e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16635588", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 335, "text": "We evaluated breath VOC biomarkers in subjects with active pulmonary TB, using an internet-linked rapid point-of-care breath test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1507, "text": "Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805989", "endSection": "abstract" }, { "offsetInBeginSection": 1671, "offsetInEndSection": 1790, "text": "A six-minute point-of-care breath test for volatile biomarkers accurately identified subjects with active pulmonary TB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22647661", "endSection": "abstract" } ] }, { "body": "What types of DNA mutations are induced by 2-hydroxy-dATP (2-OH-dATP)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14510512", "http://www.ncbi.nlm.nih.gov/pubmed/17497830", "http://www.ncbi.nlm.nih.gov/pubmed/14510499", "http://www.ncbi.nlm.nih.gov/pubmed/15133233", "http://www.ncbi.nlm.nih.gov/pubmed/10710431", "http://www.ncbi.nlm.nih.gov/pubmed/7642627", "http://www.ncbi.nlm.nih.gov/pubmed/12736306", "http://www.ncbi.nlm.nih.gov/pubmed/17439242", "http://www.ncbi.nlm.nih.gov/pubmed/15598893", "http://www.ncbi.nlm.nih.gov/pubmed/9556591", "http://www.ncbi.nlm.nih.gov/pubmed/10924147", "http://www.ncbi.nlm.nih.gov/pubmed/14750949", "http://www.ncbi.nlm.nih.gov/pubmed/18242151" ], "ideal_answer": [ "2-hydroxy-dATP mainly elicits G:C --> A:T transitions, and, to a lesser extent, G:C --> T:A transversions The induction of G:C --> T:A transversions by 2-OH-dATP indicates the formation of G*2-OH-dATP pairs. 2-OH-dATP also induces tandem (CC --> TT) mutations. Altogether, 2-OH-dATP induces both transition and transvertion mutations, such as A:T --> G:C, A:T --> C:G and G:C --> T:A mutations." ], "exact_answer": [ [ "G:C --> A:T transitions" ], [ "tandem (CC --> TT) mutations" ], [ "G:C --> T:A transversions" ], [ "A:T --> C:G mutations" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0046060", "http://www.biosemantics.org/jochem#4270178" ], "type": "list", "id": "553e1aa5a3cf796f71000003", "snippets": [ { "offsetInBeginSection": 231, "offsetInEndSection": 348, "text": "2-OH-dATP induced both transition and transversion mutations, including A:T-->G:C, A:T-->C:G and G:C-->T:A mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15133233", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 515, "text": "a G:C-->T:A transversion, the same type of mutation elicited by 2-OH-dATP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14750949", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 289, "text": "2-OH-dATP mainly elicited a G x C to A x T transition, and a G x C to T x A transversion to a lesser extent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14510512", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 400, "text": "2-OH-dATP induced mutations in a dose-dependent manner and elicited substitution and deletion mutations. Of the substitutions, a G.C-->A.T transition including a tandem (CC-->TT) mutation was mainly observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736306", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 618, "text": "2-OH-dATP elicits G.C-->T.A transversions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736306", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 632, "text": "the alpha subunit incorporated 2-OH-dATP 10 times more frequently opposite T than opposite G.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10924147", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 999, "text": "2-OH-dATP elicited G-->T transversions, indicating the formation of G*2-OH-dATP pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10710431", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 346, "text": "Interestingly, 2-OH-dATP induced both transition and transversion mutations, including A:T-->G:C, A:T-->C:G and G:C-->T:A mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15133233", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 613, "text": "The polymerase almost exclusively incorporated 8-hydroxy-dGTP (8-OH-dGTP) opposite template adenine (A) at 60% efficiency of normal dTTP incorporation, and incorporated 2-hydroxy-dATP (2-OH-dATP) opposite template thymine (T), guanine (G), or cytosine (C) at substantial rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17439242", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 295, "text": "2-OH-dATP induced mutations in a dose-dependent manner and elicited substitution and deletion mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736306", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 1014, "text": "Steady-state kinetic studies indicated that the alpha subunit incorporated 2-OH-dATP 10 times more frequently opposite T than opposite G. On the other hand, the incorporation of 2-OH-dATP opposite T by the exonuclease-deficient Klenow fragment was 2 orders of magnitude more efficient than that opposite G. These results indicate that the misinsertion specificity of 2-OH-dATP differs between replicative and repair-type DNA polymerases, and provide a biochemical basis for the mutations induced by 2-OH-dATP in E. coli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10924147", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 346, "text": "Interestingly, 2-OH-dATP induced both transition and transversion mutations, including A:T-->G:C, A:T-->C:G and G:C-->T:A mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15133233", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 295, "text": "2-OH-dATP induced mutations in a dose-dependent manner and elicited substitution and deletion mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736306", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 1068, "text": "On the other hand, in an experiment using the Klenow fragment, incorporation of 2-OH-dATP was observed only opposite T. Steady-state kinetic studies indicated that incorporation of 2-OH-dATP by DNA polymerase alpha opposite T was favored over that opposite C by a factor of only 4.5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7642627", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 296, "text": "2-OH-dATP induced mutations in a dose-dependent manner and elicited substitution and deletion mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736306", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 494, "text": "These mutations include various mutations involving a G:C-->T:A transversion, the same type of mutation elicited by 2-OH-dATP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14750949", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 295, "text": "2-OH-dATP induced mutations in a dose-dependent manner and elicited substitution and deletion mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736306", "endSection": "abstract" } ] }, { "body": "Which diseases can be treated with Afamelanotide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23277150", "http://www.ncbi.nlm.nih.gov/pubmed/19656325", "http://www.ncbi.nlm.nih.gov/pubmed/21073357", "http://www.ncbi.nlm.nih.gov/pubmed/22845050", "http://www.ncbi.nlm.nih.gov/pubmed/24256215", "http://www.ncbi.nlm.nih.gov/pubmed/20545686", "http://www.ncbi.nlm.nih.gov/pubmed/25402764", "http://www.ncbi.nlm.nih.gov/pubmed/23884489", "http://www.ncbi.nlm.nih.gov/pubmed/20565969", "http://www.ncbi.nlm.nih.gov/pubmed/25230094", "http://www.ncbi.nlm.nih.gov/pubmed/25470471", "http://www.ncbi.nlm.nih.gov/pubmed/20725548", "http://www.ncbi.nlm.nih.gov/pubmed/26132941", "http://www.ncbi.nlm.nih.gov/pubmed/23407924" ], "ideal_answer": [ "Afamelanotide was ivestigated for treatment of erythropoietic protoporphyria, vitiligo, Hailey-Hailey disease, acne vulgaris, polymorphic light eruption, prevention of actinic keratoses in organ transplant recipients and nonmelanoma skin cancer." ], "exact_answer": [ [ "erythropoietic protoporphyria" ], [ "vitiligo" ], [ "Hailey-Hailey disease" ], [ "acne vulgaris" ], [ "polymorphic light eruption" ], [ "ctinic keratoses" ], [ "nonmelanoma skin cancer" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194" ], "type": "list", "id": "56c08702ef6e394741000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Afamelanotide for Erythropoietic Protoporphyria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26132941", "endSection": "title" }, { "offsetInBeginSection": 1848, "offsetInEndSection": 2082, "text": "CONCLUSIONS: Afamelanotide had an acceptable side-effect and adverse-event profile and was associated with an increased duration of sun exposure without pain and improved quality of life in patients with erythropoietic protoporphyria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26132941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230094", "endSection": "title" }, { "offsetInBeginSection": 2195, "offsetInEndSection": 2414, "text": "CONCLUSIONS AND RELEVANCE: A combination of afamelanotide implant and NB-UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB-UV-B monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "UNLABELLED: Afamelanotide is an \u03b1-melanocyte-stimulating hormone (\u03b1-MSH) agonist with proven efficacy in photodermatoses such as erythropoietic protoporphyria (EPP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25402764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Afamelanotide (CUV1647) in dermal phototoxicity of erythropoietic protoporphyria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25470471", "endSection": "title" }, { "offsetInBeginSection": 1728, "offsetInEndSection": 1809, "text": "CONCLUSIONS: Afamelanotide is effective for the treatment of skin lesions in HHD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24256215", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1532, "text": "CONCLUSIONS: Afamelanotide appears to have anti-inflammatory effects in patients with mild-to-moderate acne vulgaris.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22845050", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 529, "text": "In a recent trial, afamelanotide administered as controlled release implants protected erythropoietic protoporphyria (EPP) patients from sunlight induced phototoxic skin reactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23277150", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1169, "text": "CONCLUSIONS: We propose that afamelanotide represents a novel and potentially effective treatment for vitiligo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23407924", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 375, "text": "Afamelanotide is currently undergoing phase II and III trials in Europe and the US for skin diseases including vitiligo, erythropoietic protoporphyria, polymorphic light eruption and prevention of actinic keratoses in organ transplant recipients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23884489", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 666, "text": "Currently, afamelanotide is already on the market in Italy and Switzerland for patients with erythropoietic protoporphyria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23884489", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1921, "text": "Agents that are showing promising results in early phases of clinical trials include betulinic acid; hedgehog signaling pathway inhibitors, such as cyclopamine and GDC-0449; alpha-melanocyte-stimulating hormone analogs, such as afamelanotide; epidermal growth factor receptor inhibitors, such as gefitinib and erlotinib; anti-epidermal growth factor receptor monoclonal antibodies, such as cetuximab and panitumumab; and the 5-fluorouracil prodrug capecitabine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20725548", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1214, "text": "Meanwhile, the regulated \u03b1-MSH analogue afamelanotide (Clinuvel Pharmaceuticals Ltd, Melbourne, Australia) is showing promise for its photoprotective potential, and is undergoing phase II and III clinical trials in people with photosensitivity disorders and those prone to nonmelanoma skin cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545686", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1467, "text": "CONCLUSIONS: Among the six models proposed to assess the effectiveness of therapeutic interventions in PP the ETFP model demonstrates the highest sensitivity using the existing data from a clinical trial of afamelanotide in PP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20565969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Afamelanotide, an agonistic analog of \u03b1-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073357", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "IMPORTANCE OF THE FIELD: Afamelanotide, an \u03b1-melanocyte stimulating hormone (MSH) agonistic analog is a first-in-class therapeutic. Its application to protoporphyria (PP), a disease associated with absolute sunlight-intolerance is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073357", "endSection": "abstract" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1242, "text": "TAKE HOME MESSAGE: Although early, results of the first trials of afamelanotide for PP are promising and the risk-safety profile appears favorable today.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073357", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 577, "text": "This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656325", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1364, "text": "The findings demonstrate beneficial effects of afamelanotide in patients with EPP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19656325", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 619, "text": "Afamelanotide is currently undergoing phase II and III trials in Europe and the US for skin diseases including vitiligo, erythropoietic protoporphyria, polymorphic light eruption and prevention of actinic keratoses in organ transplant recipients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23884489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The application of afamelanotide, an \u03b1-melanocyte stimulating hormone agonistic analogue to protoporphyria, a disease with absolute sunlight-intolerance is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25470471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "UNLABELLED: Afamelanotide is an \ufffd-melanocyte-stimulating hormone (\ufffd-MSH) agonist with proven efficacy in photodermatoses such as erythropoietic protoporphyria (EPP). This peptide drug, repeatedly administered over prolonged time, may induce anti-drug antibodies (ADA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25402764", "endSection": "abstract" }, { "offsetInBeginSection": 1743, "offsetInEndSection": 2189, "text": "Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug.CONCLUSIONS: Afamelanotide had an acceptable side-effect and adverse-event profile and was associated with an increased duration of sun exposure without pain and improved quality of life in patients with erythropoietic protoporphyria. (Funded by Clinuvel Pharmaceuticals and others; ClinicalTrials.gov numbers, NCT01605136 and NCT00979745.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26132941", "endSection": "abstract" } ] }, { "body": "Which is the mechanism used by bacteria to induce tumors in Arabidopsis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23408907", "http://www.ncbi.nlm.nih.gov/pubmed/11043469", "http://www.ncbi.nlm.nih.gov/pubmed/23593941", "http://www.ncbi.nlm.nih.gov/pubmed/11432846", "http://www.ncbi.nlm.nih.gov/pubmed/15998742", "http://www.ncbi.nlm.nih.gov/pubmed/10323222", "http://www.ncbi.nlm.nih.gov/pubmed/9090878", "http://www.ncbi.nlm.nih.gov/pubmed/19794116", "http://www.ncbi.nlm.nih.gov/pubmed/17172353", "http://www.ncbi.nlm.nih.gov/pubmed/9618535", "http://www.ncbi.nlm.nih.gov/pubmed/20696005" ], "ideal_answer": [ "The bacteria Agrobacterium tumefaciens infects Arabidopsis, as well as other plants, and induces the formation of tumors by integrating the transferred-DNA (T-DNA) region of the Ti-plasmid into the plant nuclear genome." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017360", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009617", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001419" ], "type": "summary", "id": "535917f3c95abccd6f000001", "snippets": [ { "offsetInBeginSection": 23, "offsetInEndSection": 266, "text": "Agrobacterium tumefaciens causes crown gall disease in a wide range of plant species. The neoplastic growth at the infection sites is caused by transferring, integrating, and expressing transfer DNA (T-DNA) from A. tumefaciens into plant cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593941", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 124, "text": " gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23408907", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 212, "text": "robacterium tumefaciens is a plant pathogenic bacterium that causes neoplastic growths, called 'crown gall', via the transfer and integration of transferred DNA (T-DNA) from the bacterium into the plant genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20696005", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 127, "text": "grobacterium tumefaciens causes crown gall disease by transferring and integrating bacterial DNA (T-DNA) into the plant genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19794116", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 144, "text": "ransformation of plant cells with T-DNA of virulent agrobacteria is one of the most extreme triggers of developmental changes in higher plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17172353", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 195, "text": "grobacterium tumefaciens infects plants and induces the formation of tumors called \"crown galls\" by integrating the transferred-DNA (T-DNA) region of the Ti-plasmid into the plant nuclear genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15998742", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 97, "text": "-DNA nuclear import is a central event in genetic transformation of plant cells by Agrobacterium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11432846", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 92, "text": "grobacterium tumefaciens Chry5, which is particularly virulent on soybeans, induces tumors ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11043469", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 130, "text": " have identified T-DNA tagged Arabidopsis mutants that are resistant to transformation by Agrobacterium tumefaciens (rat mutants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10323222", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 154, "text": "grobacterium tumefaciens induces crown gall tumors on plants by transferring a nucleoprotein complex, the T-complex, from the bacterium to the plant cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9618535", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 441, "text": "The recalcitrance of another ecotype occurs at a late step in T-DNA transfer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9090878", "endSection": "abstract" } ] }, { "body": "Can cffDNA be used for non-invasive testing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22720727", "http://www.ncbi.nlm.nih.gov/pubmed/22261468", "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "http://www.ncbi.nlm.nih.gov/pubmed/24204719", "http://www.ncbi.nlm.nih.gov/pubmed/21207386", "http://www.ncbi.nlm.nih.gov/pubmed/24603453", "http://www.ncbi.nlm.nih.gov/pubmed/18234572", "http://www.ncbi.nlm.nih.gov/pubmed/23024794", "http://www.ncbi.nlm.nih.gov/pubmed/23581568", "http://www.ncbi.nlm.nih.gov/pubmed/15859391", "http://www.ncbi.nlm.nih.gov/pubmed/24834709", "http://www.ncbi.nlm.nih.gov/pubmed/20840219", "http://www.ncbi.nlm.nih.gov/pubmed/22937795", "http://www.ncbi.nlm.nih.gov/pubmed/24352524", "http://www.ncbi.nlm.nih.gov/pubmed/22192861", "http://www.ncbi.nlm.nih.gov/pubmed/24482806" ], "ideal_answer": [ "Yes, cell-free fetal DNA (cffDNA) has made non-invasive prenatal testing possible." ], "exact_answer": "yes", "type": "yesno", "id": "57135fae1174fb1755000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Non-invasive prenatal testing using cell-free fetal DNA in maternal circulation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 1068, "text": "In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24352524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24204719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 532, "text": "Non-invasive prenatal aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it will achieve widespread clinical implementation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22720727", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024794", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 422, "text": "Non-invasive prenatal diagnosis (NIPD) using cell-free fetal DNA (cffDNA) in maternal plasma is an alternative to invasive prenatal diagnosis (IPD), which carries a 1% risk of miscarriage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21207386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "NIFTY (Non-invasive Fetal Trisomy Test) is a non-invasive prenatal test which is used for diagnosing fetal trisomy. The test is based on the analysis of cell free fetal DNA (cffDNA) present in the plasma and serum of a pregnant woman.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24834709", "endSection": "abstract" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1699, "text": "Using non-invasive method of cffDNAs in the shortest time possible, as well as avoiding invasive tests for early determination of fetal gender, provides the opportunity of deciding and employing early treatment for fetuses at risk of genetic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Nowadays, new advances in the use of cell free fetal DNA (cffDNA) in maternal plasma of pregnant women has provided the possibility of applying cffDNA in prenatal diagnosis as a non-invasive method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24204719", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 641, "text": "Prevention of contamination following our anti-contamination criteria is a good practice for certain non-invasive sex determination, using cffDNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23581568", "endSection": "abstract" } ] }, { "body": "List features of the Perry syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23628468", "http://www.ncbi.nlm.nih.gov/pubmed/19136952", "http://www.ncbi.nlm.nih.gov/pubmed/24881494", "http://www.ncbi.nlm.nih.gov/pubmed/20702129", "http://www.ncbi.nlm.nih.gov/pubmed/24676999", "http://www.ncbi.nlm.nih.gov/pubmed/24484619", "http://www.ncbi.nlm.nih.gov/pubmed/24343258", "http://www.ncbi.nlm.nih.gov/pubmed/20437543" ], "ideal_answer": [ "Perry syndrome is a familial parkinsonism associated with central hypoventilation, mental depression, and weight loss." ], "exact_answer": [ [ "parkinsonism" ], [ "central hypoventilation" ], [ "depression" ], [ "weight loss" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "list", "id": "56c1f034ef6e394741000050", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Depression, parkinsonism, and hypoventilation (Perry syndrome) or familial motor neuron disease have been linked to mutations in dynactin P150(Glued) (DCTN1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24676999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Perry syndrome (PS) caused by DCTN1 gene mutation is clinically characterized by autosomal dominant parkinsonism, depression, severe weight loss, and hypoventilation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24484619", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1431, "text": "CONCLUSIONS AND RELEVANCE: Mutations of the DCTN1 gene have been previously associated with amyotrophic lateral sclerosis and with Perry syndrome, a rare autosomal dominant disorder characterized by weight loss, parkinsonism, central hypoventilation, and psychiatric disturbances. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24343258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "OBJECTIVES: Perry syndrome consists of autosomal dominant Parkinsonism, depression, weight loss, and central hypoventilation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24881494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "A patient with a mood disorder and a Parkinsonian syndrome with frontal cognitive impairment thought to resemble progressive supranuclear palsy defied precise diagnosis until the development of respiratory compromise, prompting consideration of the diagnosis of Perry syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Perry syndrome is a familial parkinsonism associated with central hypoventilation, mental depression, and weight loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Perry syndrome (PS) caused by DCTN1 gene mutation is clinically characterized by autosomal dominant parkinsonism, depression, severe weight loss, and hypoventilation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24484619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Perry syndrome is a familial parkinsonism associated with central hypoventilation, mental depression, and weight loss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Perry syndrome due to the DCTN1 G71R mutation: a distinctive levodopa responsive disorder with behavioral syndrome, vertical gaze palsy, and respiratory failure", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20437543", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 445, "text": "Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19136952", "endSection": "abstract" } ] }, { "body": "Which is the main calcium binding protein of the sarcoplasmic reticulum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11058082", "http://www.ncbi.nlm.nih.gov/pubmed/19278523", "http://www.ncbi.nlm.nih.gov/pubmed/14715535", "http://www.ncbi.nlm.nih.gov/pubmed/16571864", "http://www.ncbi.nlm.nih.gov/pubmed/19230141", "http://www.ncbi.nlm.nih.gov/pubmed/1860177", "http://www.ncbi.nlm.nih.gov/pubmed/16477617", "http://www.ncbi.nlm.nih.gov/pubmed/24025332" ], "ideal_answer": [ "Calsequestrin is the major calcium-binding protein of cardiac and skeletal muscles whose function is to sequester Ca(2+ )in the lumen of the sarcoplasmic reticulum (SR).", "Calsequestrin is the major calcium-binding protein of cardiac and skeletal muscles whose function is to sequester Ca(2+ )in the lumen of the sarcoplasmic reticulum (SR). " ], "exact_answer": [ "Calsequestrin", "casq" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016529" ], "type": "factoid", "id": "54cf45e7f693c3b16b00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Calsequestrin (CS) is the low-affinity, high-capacity calcium binding protein segregated to the lumen of terminal cisternae (TC) of the sarcoplasmic reticulum (SR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16571864", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 133, "text": "human cardiac calsequestrin (CASQ2), a high-capacity calcium-binding protein located in the sarcoplasmic reticulum (SR),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14715535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Calsequestrin is the major calcium-binding protein of cardiac and skeletal muscles whose function is to sequester Ca(2+ )in the lumen of the sarcoplasmic reticulum (SR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11058082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Calsequestrin is a calcium-binding protein known to sequester calcium accumulated in the sarcoplasmic reticulum (SR) of muscle cells during relaxation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1860177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Calsequestrin (CASQ) is the major component of the sarcoplasmic reticulum (SR) lumen in skeletal and cardiac muscles. This calcium-binding protein localizes to the junctional SR (jSR) cisternae, where it is responsible for the storage of large amounts of Ca(2+)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24025332", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 317, "text": "SR calcium-regulatory proteins: (1) luminal calcium-binding proteins (calsequestrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16477617", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 587, "text": "Calsequestrin, the main calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for release through the RyR and acts as a luminal calcium sensor for the channel via its interactions with triadin and junctin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19278523", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 399, "text": "Calsequestrin, the main calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for release through the ryanodine receptor and acts as a luminal calcium sensor for the channel via its interactions with triadin and junctin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19230141", "endSection": "abstract" } ] }, { "body": "Is the UGT1A1*28 polymorphism associated with irinotecan response in Caucasians?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17762398", "http://www.ncbi.nlm.nih.gov/pubmed/22866151", "http://www.ncbi.nlm.nih.gov/pubmed/23516488", "http://www.ncbi.nlm.nih.gov/pubmed/23529007", "http://www.ncbi.nlm.nih.gov/pubmed/15286088", "http://www.ncbi.nlm.nih.gov/pubmed/22077505", "http://www.ncbi.nlm.nih.gov/pubmed/18832463", "http://www.ncbi.nlm.nih.gov/pubmed/18633245" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_5136543545370015", "o": "http://purl.uniprot.org/core/Gene" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00762", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugbank/drugs" } ], "ideal_answer": [ "Yes, it has been shown that the polymorphism UGT1A1*28 is associated with irinotecan response in Caucasians." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044465", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110", "http://www.biosemantics.org/jochem#4260100", "http://www.biosemantics.org/jochem#4231334", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020641", "http://www.uniprot.org/uniprot/UD11_HUMAN" ], "type": "yesno", "id": "51680b0e298dcd4e51000065", "snippets": [ { "offsetInBeginSection": 912, "offsetInEndSection": 980, "text": "These variants are associated with greater risk of serious toxicity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22077505", "endSection": "sections.0" }, { "offsetInBeginSection": 384, "offsetInEndSection": 507, "text": "Homozygous carriers of UGT1A1*28 as well as those with additional UGT1A variants can suffer from severe irinotecan toxicity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18832463", "endSection": "sections.0" } ] }, { "body": "For which diseases members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "http://www.ncbi.nlm.nih.gov/pubmed/22764181", "http://www.ncbi.nlm.nih.gov/pubmed/19778726", "http://www.ncbi.nlm.nih.gov/pubmed/22973455", "http://www.ncbi.nlm.nih.gov/pubmed/21913121" ], "ideal_answer": [ "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)" ], "exact_answer": [ [ "Friedreich's ataxia (FRDA)" ], [ "Huntington's disease (HD)" ] ], "type": "list", "id": "571f5d3e0fd6f91b6800000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 396, "text": "Histone deacetylase (HDAC) inhibitors have received considerable attention as potential therapeutics for a variety of cancers and neurological disorders. Recent publications on a class of pimelic diphenylamide HDAC inhibitors have highlighted their promise in the treatment of the neurodegenerative diseases Friedreich's ataxia and Huntington's disease, based on efficacy in cell and mouse models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973455", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 308, "text": "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "We recently identified a class of pimelic diphenylamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19778726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 536, "text": "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Rationale for the development of 2-aminobenzamide histone deacetylase inhibitors as therapeutics for Friedreich ataxia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22764181", "endSection": "title" }, { "offsetInBeginSection": 502, "offsetInEndSection": 804, "text": "While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 801, "text": "The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22764181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 512, "text": "While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 310, "text": "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913121", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 309, "text": "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913121", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 596, "text": "The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22764181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 310, "text": "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913121", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 597, "text": "However, histone deacetylase inhibitors tested to date either are highly cytotoxic or have very low specificities for different histone deacetylase enzymes. The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22764181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24933366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Rationale for the development of 2-aminobenzamide histone deacetylase inhibitors as therapeutics for Friedreich ataxia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22764181", "endSection": "title" }, { "offsetInBeginSection": 390, "offsetInEndSection": 597, "text": "The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22764181", "endSection": "abstract" } ] }, { "body": "Do U6-associated proteins Lsm4 and Lsm6 interact with SMN?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15526162", "http://www.ncbi.nlm.nih.gov/pubmed/10851237", "http://www.ncbi.nlm.nih.gov/pubmed/14962794", "http://www.ncbi.nlm.nih.gov/pubmed/11720283", "http://www.ncbi.nlm.nih.gov/pubmed/17178713", "http://www.ncbi.nlm.nih.gov/pubmed/23334184", "http://www.ncbi.nlm.nih.gov/pubmed/16087681", "http://www.ncbi.nlm.nih.gov/pubmed/16003501" ], "ideal_answer": [ "SMN interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6.", "yes", "SMN was found to interact with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/LSM6_LODEL", "http://www.uniprot.org/uniprot/LSM4_HUMAN", "http://www.uniprot.org/uniprot/LSM6_CRYNB", "http://www.uniprot.org/uniprot/LSM6_ASPCL", "http://www.uniprot.org/uniprot/LSM4_YEAST", "http://www.uniprot.org/uniprot/LSM4_MOUSE", "http://www.uniprot.org/uniprot/LSM4_BOVIN", "http://www.uniprot.org/uniprot/LSM6_PHANO", "http://www.uniprot.org/uniprot/LSM6_KLULA", "http://amigo.geneontology.org/amigo/term/GO:0034731", "http://www.uniprot.org/uniprot/LSM6_CHAGB", "http://www.uniprot.org/uniprot/LSM6_DEBHA", "http://www.uniprot.org/uniprot/LSM6_MOUSE", "http://www.uniprot.org/uniprot/LSM6_COPC7", "http://www.uniprot.org/uniprot/LSM6_AJECN", "http://www.uniprot.org/uniprot/LSM6_NEOFI" ], "type": "yesno", "id": "56cab4c75795f9a73e00001f", "snippets": [ { "offsetInBeginSection": 587, "offsetInEndSection": 684, "text": "SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10851237", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 682, "text": "Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10851237", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1115, "text": "Furthermore, we present evidence for two separate binding sites in SMN for Sm/Lsm proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16087681", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 684, "text": "Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10851237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11720283", "endSection": "title" }, { "offsetInBeginSection": 573, "offsetInEndSection": 790, "text": "Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. Furthermore, the carboxyl-terminal arginine- and glycine-rich domain of Lsm4 directly interacts with SMN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10851237", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 311, "text": "This entity promotes the binding of a set of factors, termed LSm/Sm proteins, onto snRNA to form the core structure of these particles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17178713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16087681", "endSection": "title" }, { "offsetInBeginSection": 770, "offsetInEndSection": 1016, "text": "In this report, we demonstrate that the coilin C-terminal domain binds directly to various Sm and Lsm proteins via their Sm motifs. We show that the region of coilin responsible for this binding activity is separable from that which binds to SMN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003501", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1454, "text": "Thus, the ability to interact with free Sm (and Lsm) proteins as well as with intact snRNPs, indicates that coilin and CBs may facilitate the modification of newly formed snRNPs, the regeneration of 'mature' snRNPs, or the reclamation of unassembled snRNP components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003501", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 748, "text": "Moreover this structure has important consequences for snRNP assembly that is mediated by two complexes containing the PRMT5 methyltransferase and the SMN (survival of motor neurons) protein, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15526162", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1372, "text": "Arginine/glycine (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are antigen targets in a variety of diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14962794", "endSection": "abstract" } ] }, { "body": "List anti-amyloid-beta monoclonal antibodies that have been investigated in clinical trials for treatment of Alzheimer disease.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21784350", "http://www.ncbi.nlm.nih.gov/pubmed/20189881", "http://www.ncbi.nlm.nih.gov/pubmed/23334069", "http://www.ncbi.nlm.nih.gov/pubmed/21263194", "http://www.ncbi.nlm.nih.gov/pubmed/22277519", "http://www.ncbi.nlm.nih.gov/pubmed/22473769", "http://www.ncbi.nlm.nih.gov/pubmed/20505438", "http://www.ncbi.nlm.nih.gov/pubmed/21504387", "http://www.ncbi.nlm.nih.gov/pubmed/19228370", "http://www.ncbi.nlm.nih.gov/pubmed/20360050", "http://www.ncbi.nlm.nih.gov/pubmed/21091109", "http://www.ncbi.nlm.nih.gov/pubmed/21592055", "http://www.ncbi.nlm.nih.gov/pubmed/23334070", "http://www.ncbi.nlm.nih.gov/pubmed/21987394", "http://www.ncbi.nlm.nih.gov/pubmed/16338209", "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "http://www.ncbi.nlm.nih.gov/pubmed/20205639", "http://www.ncbi.nlm.nih.gov/pubmed/22134132", "http://www.ncbi.nlm.nih.gov/pubmed/20154508", "http://www.ncbi.nlm.nih.gov/pubmed/23796662", "http://www.ncbi.nlm.nih.gov/pubmed/21883222", "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "http://www.ncbi.nlm.nih.gov/pubmed/22292124", "http://www.ncbi.nlm.nih.gov/pubmed/20375655", "http://www.ncbi.nlm.nih.gov/pubmed/19923550", "http://www.ncbi.nlm.nih.gov/pubmed/19585948" ], "ideal_answer": [ "Ponezumab, solanezumab and bapineuzumab are humanized antiamyloid beta (A\u03b2) monoclonal antibodies that have been designed for treatment of Alzheimer disease.", "Bapineuzumab\nSolanezumab\nPonezumab\nGantenerumab" ], "exact_answer": [ [ "Bapineuzumab", "bapineuzumab" ], [ "Solanezumab", "solanezumab" ], [ "Ponezumab", "ponezumab" ], [ "Gantenerumab" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000911", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016229", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016032", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986" ], "type": "list", "id": "52fc94db2059c6d71c000074", "snippets": [ { "offsetInBeginSection": 389, "offsetInEndSection": 528, "text": "The first active immunization clinical trial with AN1792 in AD patients was halted when a subset of patients developed meningoencephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205639", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 585, "text": "The first passive immunotherapy trial with bapineuzumab,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205639", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 402, "text": "Preliminary results of a prematurely terminated clinical trial where AD patients were actively vaccinated with aggregated Abeta ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16338209", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 203, "text": "strategies based on A\u03b21-42 peptide induced encephalomyelitis and possible microhemorrhages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23796662", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 852, "text": "Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 957, "text": "Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 995, "text": "Unfortunately, the first active vaccine (AN1792, consisting of preaggregate A\u03b2 and an immune adjuvant, QS-21) was abandoned because it caused meningoencephalitis in approximately 6% of treated patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1082, "text": "Anti-A\u03b2 monoclonal antibodies (bapineuzumab and solanezumab) are now being developed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "endSection": "abstract" }, { "offsetInBeginSection": 57, "offsetInEndSection": 321, "text": "several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22277519", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 608, "text": "Several types of A\u03b2 peptide immunotherapy for Alzheimer's disease are under investigation, direct immunization with synthetic intact A\u03b2(42) , active immunization involving the administration of synthetic fragments of A\u03b2 peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against A\u03b2 peptide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21883222", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 641, "text": "An active anti-A\u03b2 vaccine preparation, AN1792, has been used in AD patients with some clues of clinical efficacy but causing meningoencephalitis in about 6% of patients and it has been abandoned", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21592055", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1083, "text": "The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-A\u03b2 monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce A\u03b2 burden in the brain of AD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21592055", "endSection": "abstract" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1499, "text": "The results of four ongoing large Phase III trials on bapineuzumab will tell us if passive anti-A\u03b2 immunization is able to alter the course if this devastating disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21592055", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 353, "text": "Solanezumab is a monoclonal antibody that binds to \u03b2-amyloid (A\u03b2), a protein that plays a key role in the pathogenesis of AD. The drug is currently being investigated in Phase III trials as a disease-modifying treatment for AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504387", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 805, "text": "The most advanced of these immunological approaches is bapineuzumab, which is composed of humanized anti-A\u03b2 monoclonal antibodies that has been tested in two Phase II trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21091109", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1218, "text": "The results of four ongoing large Phase III trials on bapineuzumab will provide answers regarding whether passive anti-A\u03b2 immunization is able to alter the course of this devastating disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21091109", "endSection": "abstract" } ] }, { "body": "Does MVIIA and MVIIC bind to the same calcium channel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8898826", "http://www.ncbi.nlm.nih.gov/pubmed/9063691", "http://www.ncbi.nlm.nih.gov/pubmed/10694509", "http://www.ncbi.nlm.nih.gov/pubmed/20820758", "http://www.ncbi.nlm.nih.gov/pubmed/7804605", "http://www.ncbi.nlm.nih.gov/pubmed/10648826", "http://www.ncbi.nlm.nih.gov/pubmed/8853221", "http://www.ncbi.nlm.nih.gov/pubmed/16546143", "http://www.ncbi.nlm.nih.gov/pubmed/9315745", "http://www.ncbi.nlm.nih.gov/pubmed/11273667" ], "ideal_answer": [ "No, the omega-conotoxin MVIIC blocks P/Q-type calcium channels with high affinity and N-type calcium channels with low affinity, while the highly homologous omega-conotoxin MVIIA blocks only N-type calcium channels." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015220" ], "type": "yesno", "id": "56cf2a153975bb303a000004", "snippets": [ { "offsetInBeginSection": 450, "offsetInEndSection": 757, "text": "We examined the post-pubertal behavioral effects of neonatal (postnatal day 7) medial prefrontal cortex infusion of either vehicle or N-type and P/Q-type presynaptic voltage-dependent calcium channel blockers (omega-conotoxins MVIIA and MVIIC respectively; 6.8 and 45 pmol infused respectively) in rat pups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16546143", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 614, "text": "Additionally, the number of binding sites for radioligands labelling L- ([3H]nitrendipine), N- ([125I]omega-conotoxin MVIIA) and P/Q-type ([125I]omega-conotoxin MVIIC) Ca2+ channels was assessed in the rat retina and, for further comparison, in the rat cortex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11273667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Omega-conotoxin MVIIC (MVIIC) blocks P/Q-type calcium channels with high affinity and N-type calcium channels with low affinity, while the highly homologous omega-conotoxin MVIIA blocks only N-type calcium channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10648826", "endSection": "abstract" }, { "offsetInBeginSection": 1726, "offsetInEndSection": 1939, "text": "However, omega-conotoxin MVIIC seems to bind to sites different from those recognised by omega-conotoxin GVIA and MVIIA, which are markedly differentiated by their Ca2+ requirements for binding to their receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9063691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Despite their high sequence homology, the peptide neurotoxins omega-conotoxin MVIIA and MVIIC selectively block N- and P/Q-type calcium channels, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9315745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Replacement of the N-terminal half of omega-conotoxin MVIIC, a peptide blocker of P/Q-type calcium channels, with that of omega-conotoxin MVIIA significantly increased the affinity for N-type calcium channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10694509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 405, "text": " Omega-conotoxin MVIIC (MVIIC) blocks P/Q-type calcium channels with high affinity and N-type calcium channels with low affinity, while the highly homologous omega-conotoxin MVIIA blocks only N-type calcium channels. We wished to obtain MVIIC analogues more selective for P/Q-type calcium channels than MVIIC to elucidate structural differences among the channels, which discriminate the omega-conotoxins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10648826", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1643, "text": "omega-conotoxin MVIIC seems to bind to sites different from those recognised by omega-conotoxin GVIA and MVIIA,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9063691", "endSection": "abstract" } ] }, { "body": "What is the idea behind the fractal globule that has been proposed as a model of chromatin conformation in the nucleus of a cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19815776", "http://www.ncbi.nlm.nih.gov/pubmed/20461051", "http://www.ncbi.nlm.nih.gov/pubmed/22370293", "http://www.ncbi.nlm.nih.gov/pubmed/21274616", "http://www.ncbi.nlm.nih.gov/pubmed/22988072", "http://www.ncbi.nlm.nih.gov/pubmed/23781815" ], "ideal_answer": [ "The fractal globule is a compact polymer state that emerges during polymer condensation as a result of topological constraints which prevent one region of the chain from passing across another one. This long-lived intermediate state was introduced in 1988 (Grosberg et al. 1988) and has not been observed in experiments or simulations until recently (Lieberman-Aiden et al. 2009). Recent characterization of human chromatin using a novel chromosome conformational capture technique brought the fractal globule into the spotlight as a structural model of human chromosome on the scale of up to 10 Mb (Lieberman-Aiden et al. 2009). The fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus is distinct from the more commonly used globular equilibrium model and emphasizes topological constraints as a primary factor driving formation of chromosomal territories.", "The fractal globule is a compact polymer state that emerges during polymer condensation as a result of topological constraints which prevent one region of the chain from passing across another one. This long-lived intermediate state was introduced in 1988 (Grosberg et al. 1988) and has not been observed in experiments or simulations until recently (Lieberman-Aiden et al. 2009). Recent characterization of human chromatin using a novel chromosome conformational capture technique brought the fractal globule into the spotlight as a structural model of human chromosome on the scale of up to 10\u00a0Mb (Lieberman-Aiden et al. 2009). The fractal globule, a self-similar compact polymer conformation where the chain is spatially segregated on all length scales, has been proposed to result from a sudden polymer collapse. This state has gained renewed interest as one of the prime candidates for the non-entangled states of DNA molecules inside cell nuclei " ], "type": "summary", "id": "5544e4635beec11c10000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "The fractal globule, a self-similar compact polymer conformation where the chain is spatially segregated on all length scales, has been proposed to result from a sudden polymer collapse. This state has gained renewed interest as one of the prime candidates for the non-entangled states of DNA molecules inside cell nuclei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781815", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 904, "text": "Additionally, the strings and binders switch model reproduces the recently proposed \"fractal-globule\" model, but only as one of many possible transient conformations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22988072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 629, "text": "The fractal globule is a compact polymer state that emerges during polymer condensation as a result of topological constraints which prevent one region of the chain from passing across another one. This long-lived intermediate state was introduced in 1988 (Grosberg et al. 1988) and has not been observed in experiments or simulations until recently (Lieberman-Aiden et al. 2009). Recent characterization of human chromatin using a novel chromosome conformational capture technique brought the fractal globule into the spotlight as a structural model of human chromosome on the scale of up to 10\u00a0Mb (Lieberman-Aiden et al. 2009).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21274616", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1341, "text": "Next, we connect the fractal globule to recent studies that emphasize topological constraints as a primary factor driving formation of chromosomal territories. We discuss how theoretical predictions, made on the basis of the fractal globule model, can be tested experimentally. Finally, we discuss whether fractal globule architecture can be relevant for chromatin packing in other organisms such as yeast and bacteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21274616", "endSection": "abstract" }, { "offsetInBeginSection": 2260, "offsetInEndSection": 2482, "text": "Finally, ensemble analysis of the contact matrix, coupled with theoretical derivations and computational simulations, revealed that at the megabase scale Hi-C reveals features consistent with a fractal globule conformation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20461051", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 965, "text": "At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19815776", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 781, "text": "At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19815776", "endSection": "abstract" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1765, "text": "The existence of these power-laws could facilitate the formation of the recently proposed \"fractal globule\" for the confined chromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The fractal globule, a self-similar compact polymer conformation where the chain is spatially segregated on all length scales, has been proposed to result from a sudden polymer collapse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781815", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 785, "text": "At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19815776", "endSection": "abstract" }, { "offsetInBeginSection": 1628, "offsetInEndSection": 1776, "text": "The existence of these power-laws could facilitate the formation of the recently proposed \"fractal globule\" for the confined chromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "The fractal globule, a self-similar compact polymer conformation where the chain is spatially segregated on all length scales, has been proposed to result from a sudden polymer collapse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781815", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 784, "text": "At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19815776", "endSection": "abstract" } ] }, { "body": "Which anticancer drugs target human topoisomerase II?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19047165", "http://www.ncbi.nlm.nih.gov/pubmed/11724358", "http://www.ncbi.nlm.nih.gov/pubmed/22490049", "http://www.ncbi.nlm.nih.gov/pubmed/8104687", "http://www.ncbi.nlm.nih.gov/pubmed/21188112", "http://www.ncbi.nlm.nih.gov/pubmed/16450374", "http://www.ncbi.nlm.nih.gov/pubmed/8567402", "http://www.ncbi.nlm.nih.gov/pubmed/7947097", "http://www.ncbi.nlm.nih.gov/pubmed/1655244", "http://www.ncbi.nlm.nih.gov/pubmed/11850431", "http://www.ncbi.nlm.nih.gov/pubmed/8297104", "http://www.ncbi.nlm.nih.gov/pubmed/2159380", "http://www.ncbi.nlm.nih.gov/pubmed/22127645", "http://www.ncbi.nlm.nih.gov/pubmed/8996519", "http://www.ncbi.nlm.nih.gov/pubmed/1310509", "http://www.ncbi.nlm.nih.gov/pubmed/8895198", "http://www.ncbi.nlm.nih.gov/pubmed/8040892", "http://www.ncbi.nlm.nih.gov/pubmed/2154411", "http://www.ncbi.nlm.nih.gov/pubmed/10416608" ], "ideal_answer": [ "Etoposide (VP-16) and Teniposide (VM-26) are effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA. Doxorubicin, Daunorubicin and Aclarubicin are anthracyclins that act as DNA topoisomerase II inhibitors and may be used in combination. Benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity. F14512 is a polyamine-containing epipodophyllotoxin derivative that acts as an inhibitor of DNA topoisomerase II. Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II. \nAmong topoisomerase II inhibitors, the cytostatic potency was by decreasing order: mitoxantrone; doxorubicin, which was slightly greater than DuP 941, azatoxin; DuP 937; and amsacrine, which was much greater than VP-16" ], "exact_answer": [ [ "Etoposide (VP-16)" ], [ "Teniposide (VM-26)" ], [ "Doxorubicin" ], [ "Daunorubicin" ], [ "Aclarubicin" ], [ "Mitoxantrone" ], [ "Amsacrine (m-AMSA)" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003918", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004250", "http://www.disease-ontology.org/api/metadata/DOID:9974", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000372", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000373", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000371" ], "type": "list", "id": "516e5f25298dcd4e5100007d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Etoposide is effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22490049", "endSection": "sections.0" }, { "offsetInBeginSection": 312, "offsetInEndSection": 462, "text": "benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22490049", "endSection": "sections.0" }, { "offsetInBeginSection": 55, "offsetInEndSection": 119, "text": "F14512, a polyamine-containing inhibitor of DNA topoisomerase II", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22127645", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "F14512, an epipodophyllotoxin derivative equipped with a spermine moiety, is selectively taken up by the polyamine transport system over-active in tumor cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22127645", "endSection": "sections.0" }, { "offsetInBeginSection": 240, "offsetInEndSection": 615, "text": "F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. The polyamine tail supports three complementary functions: (a) facilitate formulation of a water-soluble compound, (b) increase DNA binding to reinforce topoisomerase II inhibition, and (c) facilitate selective uptake by tumor cells via the PTS", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19047165", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Twenty previously synthesized fused heterocyclic DNA-topoisomerase II (Topo II)-inhibiting compounds were investigated for their potential efficacy in various human cancer cell lines that were derived from different tumor entities", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16450374", "endSection": "sections.0" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1651, "text": "In conclusion, compounds BD 13, BD 14, BD 16, D 23 and D 24 may be useful for the treatment of different multidrug-resistant cancer cells with cross resistance against \"classical\" Topo II-targeting drugs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16450374", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "ATPase domain of eukaryotic DNA topoisomerase II. Inhibition of ATPase activity by the anti-cancer drug bisdioxopiperazine and ATP/ADP-induced dimerization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850431", "endSection": "title" }, { "offsetInBeginSection": 241, "offsetInEndSection": 325, "text": "We tested the effects of two DNA topoisomerase II poisons, etoposide and doxorubicin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11724358", "endSection": "sections.0" }, { "offsetInBeginSection": 66, "offsetInEndSection": 134, "text": "the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10416608", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II, with at least two effects on the enzyme: namely, locking it in a closed-clamp form and inhibiting its ATPase activity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10416608", "endSection": "sections.0" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1662, "text": "These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase II alpha levels and topoisomerase II catalytic activity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8996519", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Reduced expression of DNA topoisomerase II confers resistance to etoposide (VP-16) in small cell lung cancer cell lines", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8895198", "endSection": "title" }, { "offsetInBeginSection": 98, "offsetInEndSection": 184, "text": "topoisomerase II-targeting anticancer agents, etoposide (VP-16) and teniposide (VM-26)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8567402", "endSection": "sections.0" }, { "offsetInBeginSection": 76, "offsetInEndSection": 136, "text": "the anti-cancer DNA topoisomerase II poison etoposide (VP-16", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7947097", "endSection": "sections.0" }, { "offsetInBeginSection": 119, "offsetInEndSection": 288, "text": "New DNA topoisomerase II inhibitors less prone to redox reactions, such as mitoxantrone and more recently the anthrapyrazoles, were developed to circumvent this toxicity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8040892", "endSection": "sections.0" }, { "offsetInBeginSection": 301, "offsetInEndSection": 441, "text": "Two anthrapyrazoles currently in clinical evaluation, DuP 941 (Losoxantrone) and DuP 937, were compared to other topoisomerase II inhibitors", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8040892", "endSection": "sections.0" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1315, "text": "Among topoisomerase II inhibitors, the cytostatic potency was by decreasing order: mitoxantrone; doxorubicin, which was slightly greater than DuP 941, azatoxin; DuP 937; and amsacrine, which was much greater than VP-16", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8040892", "endSection": "sections.0" }, { "offsetInBeginSection": 1, "offsetInEndSection": 185, "text": "n an attempt to clarify the role of drug-induced protein-associated DNA breaks (i.e., DNA topoisomerase II-mediated DNA cleavage) in the cytotoxic activity of doxorubicin and etoposide", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2154411", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "The effect of combinations of the anthracycline aclarubicin and the topoisomerase II targeting drugs 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside) (VP-16) and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) was investigated in a clonogenic assay", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2159380", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "Antagonistic effect of aclarubicin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2159380", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "The effect of combinations of the anthracyclines aclarubicin and daunorubicin was investigated in a clonogenic assay using the human small cell lung cancer cell line OC-NYH and a multidrug-resistant (MDR) murine subline of Ehrlich ascites tumor (EHR2/DNR+)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1655244", "endSection": "sections.0" }, { "offsetInBeginSection": 363, "offsetInEndSection": 459, "text": "the DNA topoisomerase II inhibitors doxorubicin and etoposide in both types of cancer cell lines", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1310509", "endSection": "sections.0" }, { "offsetInBeginSection": 28, "offsetInEndSection": 121, "text": "the DNA topoisomerase II inhibitors doxorubicin and etoposide in human lung cancer cell lines", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1310509", "endSection": "title" }, { "offsetInBeginSection": 427, "offsetInEndSection": 523, "text": "cells are cross-resistant to some drugs that interact with topoisomerase II but not mitoxantrone", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8104687", "endSection": "sections.0" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1380, "text": "suramin decreases the phosphorylation of Topo II mediated by PKC. This effect of suramin might cause the inhibition of Topo II activity resulting in the growth inhibition of tumor cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8297104", "endSection": "sections.0" } ] }, { "body": "What is SHAPE-Seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23788555", "http://www.ncbi.nlm.nih.gov/pubmed/21642531", "http://www.ncbi.nlm.nih.gov/pubmed/21642536", "http://www.ncbi.nlm.nih.gov/pubmed/25303992" ], "ideal_answer": [ "SHAPE-Seq is a high-throughput technique that can simultaneously measure quantitative, single nucleotide-resolution secondary and tertiary structural information for hundreds of RNA molecules of arbitrary sequence. SHAPE-Seq combines selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry with multiplexed paired-end deep sequencing of primer extension products. This generates millions of sequencing reads, which are then analyzed using a fully automated data analysis pipeline, based on a rigorous maximum likelihood model of the SHAPE-Seq experiment. SHAPE-Seq has the ability to accurately infer secondary and tertiary structural information, detect subtle conformational changes due to single nucleotide point mutations, and simultaneously measure the structures of a complex pool of different RNA molecules. SHAPE-Seq thus represents a powerful step toward making the study of RNA secondary and tertiary structures high throughput and accessible to a wide array of scientific pursuits, from fundamental biological investigations to engineering RNA for synthetic biological systems. SHAPE-Seq v2.0 is a 'universal' method that can obtain reactivity information for every nucleotide of an RNA without having to use or introduce a specific reverse transcriptase priming site within the RNA. It is a highly reproducible method, with reactivity data that can be used as constraints in RNA folding algorithms to predict structures on par with those generated using data from other SHAPE methods. SHAPE-Seq v2.0 is expected to be broadly applicable to understanding the RNA sequence-structure relationship at the heart of some of life's most fundamental processes." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0010501", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057166", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059014" ], "type": "summary", "id": "56af573b0a360a5e45000011", "snippets": [ { "offsetInBeginSection": 168, "offsetInEndSection": 1040, "text": "This article contains a protocol for selective 2'-hydroxyl acylation analyzed by primer extension and sequencing (SHAPE-Seq) that, through a combination of structure-dependent chemical probing and next-generation sequencing technologies, achieves structural characterization of hundreds of RNAs in a single experiment. This protocol is applicable in a variety of conditions, and represents an important tool for understanding RNA biology. The protocol includes methods for the design and synthesis of RNA mixtures for study, and the construction and analysis of structure-dependent sequencing libraries that reveal structural information of the RNAs in the mixtures. The methods are generally applicable to studying RNA structure and interactions in vitro in a variety of conditions, and allows for the rapid characterization of RNA structures in a high-throughput manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23788555", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 696, "text": "We focus on a novel assay utilizing this approach, called selective 2'-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq), that can be used to characterize RNA secondary and tertiary structure. We describe a fully automated data analysis pipeline for SHAPE-Seq analysis that includes read processing, mapping, and structural inference based on a model of the experiment. Our methods rely on the solution of a series of convex optimization problems for which we develop efficient and effective numerical algorithms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642536", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 1464, "text": "We have developed a high-throughput technique, SHAPE-Seq, that can simultaneously measure quantitative, single nucleotide-resolution secondary and tertiary structural information for hundreds of RNA molecules of arbitrary sequence. SHAPE-Seq combines selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry with multiplexed paired-end deep sequencing of primer extension products. This generates millions of sequencing reads, which are then analyzed using a fully automated data analysis pipeline, based on a rigorous maximum likelihood model of the SHAPE-Seq experiment. We demonstrate the ability of SHAPE-Seq to accurately infer secondary and tertiary structural information, detect subtle conformational changes due to single nucleotide point mutations, and simultaneously measure the structures of a complex pool of different RNA molecules. SHAPE-Seq thus represents a powerful step toward making the study of RNA secondary and tertiary structures high throughput and accessible to a wide array of scientific pursuits, from fundamental biological investigations to engineering RNA for synthetic biological systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642531", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 1350, "text": "As part of this optimization, we present SHAPE-Seq v2.0, a 'universal' method that can obtain reactivity information for every nucleotide of an RNA without having to use or introduce a specific reverse transcriptase priming site within the RNA. We show that SHAPE-Seq v2.0 is highly reproducible, with reactivity data that can be used as constraints in RNA folding algorithms to predict structures on par with those generated using data from other SHAPE methods. We anticipate SHAPE-Seq v2.0 to be broadly applicable to understanding the RNA sequence-structure relationship at the heart of some of life's most fundamental processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303992", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1464, "text": "We demonstrate the ability of SHAPE-Seq to accurately infer secondary and tertiary structural information, detect subtle conformational changes due to single nucleotide point mutations, and simultaneously measure the structures of a complex pool of different RNA molecules. SHAPE-Seq thus represents a powerful step toward making the study of RNA secondary and tertiary structures high throughput and accessible to a wide array of scientific pursuits, from fundamental biological investigations to engineering RNA for synthetic biological systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642531", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1464, "text": "SHAPE-Seq thus represents a powerful step toward making the study of RNA secondary and tertiary structures high throughput and accessible to a wide array of scientific pursuits, from fundamental biological investigations to engineering RNA for synthetic biological systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642531", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 731, "text": "We have developed a high-throughput technique, SHAPE-Seq, that can simultaneously measure quantitative, single nucleotide-resolution secondary and tertiary structural information for hundreds of RNA molecules of arbitrary sequence. SHAPE-Seq combines selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry with multiplexed paired-end deep sequencing of primer extension products.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642531", "endSection": "abstract" }, { "offsetInBeginSection": 732, "offsetInEndSection": 1196, "text": "This generates millions of sequencing reads, which are then analyzed using a fully automated data analysis pipeline, based on a rigorous maximum likelihood model of the SHAPE-Seq experiment. We demonstrate the ability of SHAPE-Seq to accurately infer secondary and tertiary structural information, detect subtle conformational changes due to single nucleotide point mutations, and simultaneously measure the structures of a complex pool of different RNA molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642531", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1470, "text": "We demonstrate the ability of SHAPE-Seq to accurately infer secondary and tertiary structural information, detect subtle conformational changes due to single nucleotide point mutations, and simultaneously measure the structures of a complex pool of different RNA molecules. SHAPE-Seq thus represents a powerful step toward making the study of RNA secondary and tertiary structures high throughput and accessible to a wide array of scientific pursuits, from fundamental biological investigations to engineering RNA for synthetic biological systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21642531", "endSection": "abstract" } ] }, { "body": "Which are the known inhibitors of the TPL2/MAP3K8 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17664070", "http://www.ncbi.nlm.nih.gov/pubmed/16165349", "http://www.ncbi.nlm.nih.gov/pubmed/23828905", "http://www.ncbi.nlm.nih.gov/pubmed/21851209", "http://www.ncbi.nlm.nih.gov/pubmed/21862328", "http://www.ncbi.nlm.nih.gov/pubmed/21705614", "http://www.ncbi.nlm.nih.gov/pubmed/19217782", "http://www.ncbi.nlm.nih.gov/pubmed/20606319", "http://www.ncbi.nlm.nih.gov/pubmed/20045951", "http://www.ncbi.nlm.nih.gov/pubmed/19464884", "http://www.ncbi.nlm.nih.gov/pubmed/21742493", "http://www.ncbi.nlm.nih.gov/pubmed/17715908", "http://www.ncbi.nlm.nih.gov/pubmed/18755587" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q63562", "o": "http://linkedlifedata.com/resource/#_51363335363200E" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_51363335363200E", "o": "Tpl2" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_51363335363200C", "o": "TPL-2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51363335363200B", "o": "Mitogen-activated protein kinase kinase kinase 8" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51363335363200C", "o": "Tumor progression locus 2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51363335363200E", "o": "Map3k8" } ], "ideal_answer": [ "[1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles were the first Tumor Progression Loci-2 (Tpl2) kinase inhibitors. 4-alkylamino-[1,7]naphthyridine-3-carbonitriles are also known to inhibit Tpl2 function as well as quinoline-3-carbonitrile derivatives, thieno[3,2-d]pyrimidines and 2,4-disubstituted thieno[2,3-c]pyridines, indazoles, 4-Alkylamino-[1,7]naphthyridine-3-carbonitriles and generally molecules belonging to the wide categories of quinoline-3-carbonitriles, indazoles and thieno-pyrimidines.", "Honokiol\nThieno[3,2-d]pyrimidines and thieno[2,3-c]pyridine\nQuinoline-3-carbonitrile derivatives (8-halo-4-(3-chloro-4-fluoro-phenylamino)-6-[(1H-[1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles; 8-bromo-4-(3-chloro-4-fluorophenylamino)-6-[(1-methyl-1H-imidazol-4-yl)methylamino]quinoline-3-carbonitrile; 4-alkylamino-[1,7]naphthyridine-3-carbonitrile; 1,7-naphthyridine-3-carbonitriles)\nIndazoles\nLuteolin\n1,7-naphtyridine-3-carbonitrile" ], "exact_answer": [ [ "Honokiol" ], [ "Thieno[3,2-d]pyrimidines and thieno[2,3-c]pyridine", "thieno-pyrimidines" ], [ "Quinoline-3-carbonitrile derivatives (8-halo-4-(3-chloro-4-fluoro-phenylamino)-6-[(1H-[1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles", "quinoline-3-carbonitriles" ], [ "8-bromo-4-(3-chloro-4-fluorophenylamino)-6-[(1-methyl-1H-imidazol-4-yl)methylamino]quinoline-3-carbonitrile; 4-alkylamino-[1,7]naphthyridine-3-carbonitrile; 1,7-naphthyridine-3-carbonitriles)" ], [ "Indazoles", "indazoles" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033673", "http://www.uniprot.org/uniprot/M3K8_RAT", "http://www.uniprot.org/uniprot/M3K8_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047428", "http://www.uniprot.org/uniprot/M3K8_HUMAN" ], "type": "list", "id": "52fc8b772059c6d71c00006e", "snippets": [ { "offsetInBeginSection": 1629, "offsetInEndSection": 1821, "text": "Taken together, our results suggest that the therapeutic inhibition of Tpl2 by Honokiol thwarts both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23828905", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 337, "text": "The article describes the development of a robust pharmacophore model and the investigation of structure-activity relationship analysis of quinoline-3-carbonitrile derivatives reported for Tpl2 kinase inhibition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21851209", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 613, "text": "In the present study, we found that luteolin inhibited TNF-\u03b1-induced COX-2 expression by down-regulating the transactivation of nuclear factor-\u03baB and activator protein-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21705614", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 622, "text": "we studied the molecular mechanisms of Tpl2-mediated TNFalpha production using a potent Tpl2 kinase inhibitor, 1,7-naphtyridine-3-carbonitrile, and LPS-stimulated RAW264.7 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20606319", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 332, "text": "a selective and potent inhibitor of Tpl2, 1,7-naphtyridine-3-carbonitrile, was used", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20045951", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 335, "text": "We have discovered that 8-halo-4-(3-chloro-4-fluoro-phenylamino)-6-[(1H-[1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles (4) are potent inhibitors of this enzyme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464884", "endSection": "abstract" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1526, "text": "urther structure-activity based modifications led to the identification of 8-bromo-4-(3-chloro-4-fluorophenylamino)-6-[(1-methyl-1H-imidazol-4-yl)methylamino]quinoline-3-carbonitrile, which demonstrated in vitro as well as in vivo efficacy in inhibition of LPS-induced TNF-alpha production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17715908", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 224, "text": "nhibitors of tumor progression loci-2 (Tpl2) kinase and tumor necrosis factor alpha (TNF-alpha) production: selectivity and in vivo antiinflammatory activity of novel 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17715908", "endSection": "title" }, { "offsetInBeginSection": 42, "offsetInEndSection": 92, "text": "thieno[3,2-d]pyrimidines as Tpl2 kinase inhibitors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862328", "endSection": "title" }, { "offsetInBeginSection": 19, "offsetInEndSection": 75, "text": " selective thieno[2,3-c]pyridine inhibitor of COT kinase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19217782", "endSection": "title" }, { "offsetInBeginSection": 199, "offsetInEndSection": 311, "text": "we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitrile", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664070", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 89, "text": "nhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16165349", "endSection": "title" } ] }, { "body": "What is the mode of inheritance in Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22693659", "http://www.ncbi.nlm.nih.gov/pubmed/8987005", "http://www.ncbi.nlm.nih.gov/pubmed/3369448", "http://www.ncbi.nlm.nih.gov/pubmed/22959745", "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "http://www.ncbi.nlm.nih.gov/pubmed/939547", "http://www.ncbi.nlm.nih.gov/pubmed/19549413", "http://www.ncbi.nlm.nih.gov/pubmed/11128621", "http://www.ncbi.nlm.nih.gov/pubmed/17924555", "http://www.ncbi.nlm.nih.gov/pubmed/16675878" ], "ideal_answer": [ "Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked ", "Fanconi anemia (FA) is a rare inherited syndrome. So far, fifteen genetic subtypes have been distinguished. The mode of inheritance for all subtypes is autosomal recessive, except for FANCB, which is X-linked." ], "exact_answer": [ "Autosomal recessive, except for FANCB, which is X-linked." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "factoid", "id": "54ede95c94afd6150400000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Fanconi anemia (FA) is a recessively inherited syndrome with predisposition to bone marrow failure and malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17924555", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 626, "text": "Original Fanconi anemia data, for which no information about the ascertainment was available, were then analyzed, with results that confirmed a monogenic autosomal recessive mode of inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3369448", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 309, "text": "The formal genetics of Fanconi's anemia were investigated on the basis of 21 families from different European countries, and of 69 families from the literature. CONCLUSIONS: 1. The result of segregation analysis is compatible with the hypothesis of a simple autosomal recessive mode of inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/939547", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 624, "text": " Original Fanconi anemia data, for which no information about the ascertainment was available, were then analyzed, with results that confirmed a monogenic autosomal recessive mode of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3369448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "X-linked inheritance of Fanconi anemia complementation group B.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Fanconi anemia (FA) is a rare genetic disease with both autosomal and X-linked inheritance, characterized by genomic instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549413", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1001, "text": " X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 627, "text": "Original Fanconi anemia data, for which no information about the ascertainment was available, were then analyzed, with results that confirmed a monogenic autosomal recessive mode of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3369448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Fanconi anemia (FA), a recessive syndrome with both autosomal and X-linked inheritance, features diverse clinical symptoms, such as progressive bone marrow failure, hypersensitivity to DNA cross-linking agents, chromosomal instability and susceptibility to cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675878", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1210, "text": "X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B. Its presence as a single active copy and essentiality for a functional Fanconi anemia-BRCA pathway make FANCB a potentially vulnerable component of the cellular machinery that maintains genomic integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Fanconi anemia (FA) is a rare genetic disease, transmitted in an autosomal recessive mode.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22959745", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 200, "text": "Report of two early-onset cases with Fanconis anemia-like phenotypes suggesting an autosomal-recessive inheritance pattern.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11128621", "endSection": "title" }, { "offsetInBeginSection": 264, "offsetInEndSection": 436, "text": "In the first family, an association with Fanconis anemia was observed in three of seven pregnancies (2 boys, 1 girl) suggesting an autosomal recessive mode of transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8987005", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 339, "text": "The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693659", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1007, "text": "X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 338, "text": "The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693659", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 436, "text": "In the first family, an association with Fanconi's anemia was observed in three of seven pregnancies (2 boys, 1 girl) suggesting an autosomal recessive mode of transmission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8987005", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1006, "text": "X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Fanconi anemia (FA) is a rare genetic disease, transmitted in an autosomal recessive mode", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22959745", "endSection": "abstract" } ] }, { "body": "Describe the involvement of conserved noncoding sequences in the regulation of Hox genes.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21688387", "http://www.ncbi.nlm.nih.gov/pubmed/24043829", "http://www.ncbi.nlm.nih.gov/pubmed/10677514", "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "http://www.ncbi.nlm.nih.gov/pubmed/15867430", "http://www.ncbi.nlm.nih.gov/pubmed/14707166", "http://www.ncbi.nlm.nih.gov/pubmed/12799348", "http://www.ncbi.nlm.nih.gov/pubmed/20616144", "http://www.ncbi.nlm.nih.gov/pubmed/18791732", "http://www.ncbi.nlm.nih.gov/pubmed/16636282", "http://www.ncbi.nlm.nih.gov/pubmed/15509224" ], "ideal_answer": [ "Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes. The b-paralogs of the duplicated fugu Hox clusters are virtually devoid of unique ancient CNEs. Elephant shark and human Hox clusters have lost fewer ancient CNEs. If these ancient CNEs are indeed enhancers directing tissue-specific expression of Hox genes, divergence of their sequences in vertebrate lineages might have led to altered expression patterns and presumably the functions of their associated Hox genes. When compared, the amphioxus Hox cluster with the human HoxA, HoxB, HoxC, and HoxD clusters were found to have several conserved noncoding regions, both in intergenic and intronic regions. This suggests that the regulation of Hox genes is highly conserved across chordates, consistent with the similar Hox expression patterns in vertebrates and amphioxus." ], "type": "summary", "id": "553ccbaef32186855800000f", "snippets": [ { "offsetInBeginSection": 948, "offsetInEndSection": 1130, "text": " The data presented herein identify many noncoding sequence motifs conserved over 800 million years that may function as genetic control motifs essential to the developmental process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10677514", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1295, "text": "by comparing conserved noncoding sequences upstream of these exons in different species, we were able to identify homology between some exons. Some alternative splicing variants are probably very ancient and were already coded for by the ancestral Hox gene cluster", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20616144", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 886, "text": "Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1174, "text": "the b-paralogs of the duplicated fugu Hox clusters are virtually devoid of unique ancient CNEs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1529, "text": "elephant shark and human Hox clusters have lost fewer ancient CNEs. If these ancient CNEs are indeed enhancers directing tissue-specific expression of Hox genes, divergence of their sequences in vertebrate lineages might have led to altered expression patterns and presumably the functions of their associated Hox genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Unexpectedly large number of conserved noncoding regions within the ancestral chordate Hox cluster", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18791732", "endSection": "title" }, { "offsetInBeginSection": 373, "offsetInEndSection": 575, "text": "We found that Hox intergenic regions are largely conserved between the two amphioxus species, especially in the case of genes located at the 3' of the cluster, a trend previously observed in vertebrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18791732", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 926, "text": "We further compared the amphioxus Hox cluster with the human HoxA, HoxB, HoxC, and HoxD clusters, finding several conserved noncoding regions, both in intergenic and intronic regions. This suggests that the regulation of Hox genes is highly conserved across chordates, consistent with the similar Hox expression patterns in vertebrates and amphioxus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18791732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Highly conserved syntenic blocks at the vertebrate Hox loci and conserved regulatory elements within and outside Hox gene clusters", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16636282", "endSection": "title" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1530, "text": "A large number of CNS was identified within the Hox clusters and outside the Hox clusters spread over large regions. The CNS include previously characterized enhancers and overlap with the 5' global control regions of HoxA and HoxD clusters. Most of the CNS are likely to be control regions involved in the regulation of Hox and other genes in these loci. We propose that the regulatory elements spread across large regions on either side of Hox clusters are a major evolutionary constraint that has maintained the exceptionally long syntenic blocks at the HoxA and HoxD loci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16636282", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 1032, "text": "omparative sequence analysis between homologous human and mouse genomic sequence upstream of Hoxa13 revealed a remote 2.25-kb conserved noncoding sequence (mmA13CNS) within the fourth intron of the Hibadh gene. mmA13CNS shares a common 131-bp core identity within a conserved noncoding sequence upstream of Hoxd13, which is located within the previously identified distal limb enhancer critical region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15509224", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1050, "text": "HoxA cluster noncoding sequences conserved between bichir and euteleosts indicate that novel cis-sequences were acquired in the stem actinopterygians and maintained after cluster duplication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14707166", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 882, "text": "Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Unexpectedly large number of conserved noncoding regions within the ancestral chordate Hox cluster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18791732", "endSection": "title" }, { "offsetInBeginSection": 573, "offsetInEndSection": 757, "text": "We further compared the amphioxus Hox cluster with the human HoxA, HoxB, HoxC, and HoxD clusters, finding several conserved noncoding regions, both in intergenic and intronic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18791732", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 956, "text": "Then, a plethora of conserved noncoding sequences, which are putative enhancers, were identified around the three Hox genes closer to the splits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15867430", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 757, "text": "We have generated a comprehensive database of conserved Hox noncoding sequences that include cartilaginous, lobe-finned, and ray-finned fishes (bichir and teleosts).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21688387", "endSection": "abstract" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1330, "text": "Several conserved noncoding elements (CNEs) were predicted in the Hox clusters of lamprey, elephant shark, and human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24043829", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 887, "text": "Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 761, "text": "We have generated a comprehensive database of conserved Hox noncoding sequences that include cartilaginous, lobe-finned, and ray-finned fishes (bichir and teleosts).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21688387", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 964, "text": "Then, a plethora of conserved noncoding sequences, which are putative enhancers, were identified around the three Hox genes closer to the splits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15867430", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 840, "text": "Comparative sequence analysis between homologous human and mouse genomic sequence upstream of Hoxa13 revealed a remote 2.25-kb conserved noncoding sequence (mmA13CNS) within the fourth intron of the Hibadh gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15509224", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1183, "text": "We found that although bichir possesses four Hox gene clusters, its pattern of conservation of noncoding sequences is mosaic between outgroups, such as human, coelacanth, and shark, with four Hox gene clusters and teleosts, such as zebrafish and pufferfish, with seven or eight Hox gene clusters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21688387", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 963, "text": "Then, a plethora of conserved noncoding sequences, which are putative enhancers, were identified around the three Hox genes closer to the splits", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15867430", "endSection": "abstract" } ] }, { "body": "Give an overview of visualizing genomes with oligopaint FISH probes.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24510436", "http://www.ncbi.nlm.nih.gov/pubmed/23236188" ], "ideal_answer": [ "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases. Coupled with fluorescence in situ hybridization (FISH) and a bioinformatic platform, this technology could be extended to any organism whose genome has been sequenced. The oligonucleotide probes are renewable, highly efficient, and able to robustly label chromosomes in cell culture, fixed tissues, and metaphase spreads. The method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of chromosomal regions. It is anticipated that this technology will lead to an enhanced ability to visualize interphase and metaphase chromosomes." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015345" ], "type": "summary", "id": "56c0ea0aef6e394741000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510436", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 1049, "text": "Here, we describe an oligonucleotide- and PCR-based strategy for fluorescence in situ hybridization (FISH) and a bioinformatic platform that enables this technology to be extended to any organism whose genome has been sequenced. The oligonucleotide probes are renewable, highly efficient, and able to robustly label chromosomes in cell culture, fixed tissues, and metaphase spreads. Our method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of regions ranging from tens of kilobases to megabases with the same basic protocol. We anticipate this technology will lead to an enhanced ability to visualize interphase and metaphase chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23236188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases. This unit details how Oligopaint probes can be synthesized using basic molecular biological techniques, and provides protocols for FISH, 3D-FISH, and sample preparation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases. This unit details how Oligopaint probes can be synthesized using basic molecular biological techniques, and provides protocols for FISH, 3D-FISH, and sample preparation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510436", "endSection": "abstract" } ] }, { "body": "What is Targeted Chromatin Capture (T2C)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25031611", "http://www.ncbi.nlm.nih.gov/pubmed/24561620" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0039007", "o": "D002843" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067863", "o": "D006570" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067865", "o": "D006570" } ], "ideal_answer": [ "Targeted Chromatin Capture (T2C) is an efficient, easy, and affordable with high (restriction fragment) resolution tool to address both genome compartmentalization and chromatin-interaction networks for specific genomic regions at high resolution for both clinical and non-clinical research.", "Significant efforts have recently been put into the investigation of the spatial organization and the chromatin-interaction networks of genomes. T2C provides an unbiased view of the spatial organization of selected loci at superior resolution (single restriction fragment resolution, from 2 to 6 kbp) at much lower costs than Hi-C due to the lower sequencing effort." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057166", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002843", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047369", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003850", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022041", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006570" ], "type": "summary", "id": "56a38f9b496b62f23f000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Targeted Chromatin Capture (T2C): a novel high resolution high throughput method to detect genomic interactions and regulatory elements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031611", "endSection": "title" }, { "offsetInBeginSection": 558, "offsetInEndSection": 907, "text": " Here we describe a new technique termed Targeted Chromatin Capture (T2C), to interrogate large selected regions of the genome. T2C provides an unbiased view of the spatial organization of selected loci at superior resolution (single restriction fragment resolution, from 2 to 6 kbp) at much lower costs than Hi-C due to the lower sequencing effort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031611", "endSection": "abstract" }, { "offsetInBeginSection": 2081, "offsetInEndSection": 2343, "text": "T2C is an efficient, easy, and affordable with high (restriction fragment) resolution tool to address both genome compartmentalization and chromatin-interaction networks for specific genomic regions at high resolution for both clinical and non-clinical research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031611", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 794, "text": "Here we describe a new technique termed Targeted Chromatin Capture (T2C), to interrogate large selected regions of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031611", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 674, "text": "Here we describe a new technique termed Targeted Chromatin Capture (T2C), to interrogate large selected regions of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031611", "endSection": "abstract" } ] }, { "body": "What are the reported adverse effects of topical minoxidil?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11807448", "http://www.ncbi.nlm.nih.gov/pubmed/17902730", "http://www.ncbi.nlm.nih.gov/pubmed/9039309", "http://www.ncbi.nlm.nih.gov/pubmed/3191000", "http://www.ncbi.nlm.nih.gov/pubmed/3800424", "http://www.ncbi.nlm.nih.gov/pubmed/15034503", "http://www.ncbi.nlm.nih.gov/pubmed/11041102", "http://www.ncbi.nlm.nih.gov/pubmed/3311578", "http://www.ncbi.nlm.nih.gov/pubmed/17324826", "http://www.ncbi.nlm.nih.gov/pubmed/15982234", "http://www.ncbi.nlm.nih.gov/pubmed/2256586", "http://www.ncbi.nlm.nih.gov/pubmed/1554931", "http://www.ncbi.nlm.nih.gov/pubmed/23463948", "http://www.ncbi.nlm.nih.gov/pubmed/3549808", "http://www.ncbi.nlm.nih.gov/pubmed/8050148", "http://www.ncbi.nlm.nih.gov/pubmed/21939432", "http://www.ncbi.nlm.nih.gov/pubmed/22592723" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10920929", "o": "645145" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1724451", "o": "http://linkedlifedata.com/resource/umls/label/A10920929" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1724451", "o": "http://linkedlifedata.com/resource/umls/label/A10920929" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10920929", "o": "Minoxidil Topical Foam" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10488268", "o": "372937" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1246998", "o": "http://linkedlifedata.com/resource/umls/label/A10488268" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10488268", "o": "Minoxidil Topical Solution" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1246998", "o": "http://linkedlifedata.com/resource/umls/label/A10488268" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10920929", "o": "RXNORM" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1879182", "o": "http://linkedlifedata.com/resource/umls/id/C1724451" }, { "p": 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"http://linkedlifedata.com/resource/umls/label/A1542854", "o": "Multum" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10655637", "o": "RXNORM" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C2920933", "o": "http://linkedlifedata.com/resource/umls/id/C1246998" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2920933", "o": "http://linkedlifedata.com/resource/umls/label/A18089996" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18089996", "o": "Minoxidil Topical Solution [Vitadil 2A]" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18089996", "o": "999726" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10655638", "o": "RXNORM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18089996", "o": "RXNORM" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C1246998", "o": "http://linkedlifedata.com/resource/umls/id/C0307514" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C1724451", "o": "http://linkedlifedata.com/resource/umls/id/C1879182" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C1246998", "o": "http://linkedlifedata.com/resource/umls/id/C1239337" } ], "ideal_answer": [ "Typical side effects of this topical treatment include irritative dermatitis going along with pruritus, erythema, scaling and dryness, which occur especially at the onset of the therapy. In some cases, allergic contact dermatitis or exacerbation of seborrheic dermatitis has been reported.\nHypertrichosis is a well-recognized adverse effect of therapy with either oral or topical minoxidil.\nWe observed an as yet unreported \"polymyalgia syndrome\" in four otherwise healthy males whose sole medication was topically applied minoxidil. They experienced fatigue, weight loss and severe pain in the shoulders and pelvic girdle, suggesting connective tissue disease. Three patients had a transient rise in liver enzymes, while other laboratory analyses remained normal. Tritanomaly was detected in two patients who underwent systematic color vision testing.\nA case of central serous chorioretinopathy after application of topical minoxidil solution.\nA case of acute myocardial infarction associated with topical use of minoxidil (RiUP) for treatment of baldness.\nCompared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2).\nTwo of our patients developed smoking intolerance during treatment with topical minoxidil for androgenital alopecia." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064420", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008914" ], "type": "summary", "id": "5324d0429b2d7acc7e000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Hypertrichosis is a well-recognized adverse effect of therapy with either oral or topical minoxidil.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463948", "endSection": "abstract" }, { "offsetInBeginSection": 2102, "offsetInEndSection": 2226, "text": "reported increase of adverse events (additional hair growth on areas other than the scalp) with minoxidil (5%) twice daily. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22592723", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 205, "text": "a case of central serous chorioretinopathy after application of topical minoxidil solution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21939432", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1007, "text": "One month after the drug was discontinued, normal findings were found upon reexamination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21939432", "endSection": "abstract" }, { "offsetInBeginSection": 1787, "offsetInEndSection": 1894, "text": "The incidence of adverse effects such as pruritus or local irritation was similar in the 5% minoxidil group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17902730", "endSection": "abstract" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1548, "text": "The patients tolerated treatment with 1% topical minoxidil well without significant adverse effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17324826", "endSection": "abstract" }, { "offsetInBeginSection": 1626, "offsetInEndSection": 1779, "text": "An increased occurrence of pruritus, local irritation, and hypertrichosis was observed with 5% topical minoxidil versus 2% topical minoxidil and placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15034503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Allergic contact dermatitis to topical minoxidil solution: etiology and treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11807448", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 626, "text": "However, some patients present with complaints of pruritus and scaling of the scalp. The most common causes of these symptoms include irritant contact dermatitis, allergic contact dermatitis, or an exacerbation of seborrheic dermatitis. Patients suffering from allergic contact dermatitis may benefit from patch testing to determine the causative allergen. Among the patients we patch tested, propylene glycol was found to be the contactant in a majority of cases, not the minoxidil itself. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11807448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "A case of acute myocardial infarction associated with topical use of minoxidil (RiUP) for treatment of baldness.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11041102", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "A 45-year-old Japanese man with paroxysmal atrial fibrillation (AF) developed acute anteroseptal myocardial infarction (MI). He had used 1% topical minoxidil (RiUP) once a day for 4 months before the onset of MI for treatment of baldness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11041102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Diffuse hypertrichosis during treatment with 5% topical minoxidil.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9039309", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Five women affected by androgenetic alopecia developed severe hypertrichosis of the face and limbs after 2-3 months of treatment with 5% topical minoxidil. Minoxidil was discontinued and in all patients the hypertrichosis disappeared from the face and arms after 1-3 months, and from legs after 4-5 months", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9039309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Generalized hypertrichosis after treatment with topical minoxidil.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8050148", "endSection": "title" }, { "offsetInBeginSection": 106, "offsetInEndSection": 440, "text": "hypertrichosis is uncommon after treatment with topical minoxidil for alopecia, and normally only occurs in areas close to the site of application. A 16-year-old girl is presented who developed generalized hypertrichosis 3 months after applying topical minoxidil for treatment of diffuse alopecia in doses greater than that prescribed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8050148", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 511, "text": "Two of our patients developed smoking intolerance during treatment with topical minoxidil for androgenital alopecia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1554931", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 711, "text": "The relation between treatment with minoxidil and smoking intolerance was emphasized by stopping treatment and the disappearance of the smoking intolerance, and then by rechallenge in both patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1554931", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 719, "text": "We observed an as yet unreported \"polymyalgia syndrome\" in four otherwise healthy males whose sole medication was topically applied minoxidil. They experienced fatigue, weight loss and severe pain in the shoulders and pelvic girdle, suggesting connective tissue disease. Three patients had a transient rise in liver enzymes, while other laboratory analyses remained normal. Tritanomaly was detected in two patients who underwent systematic color vision testing. All symptoms disappeared after withdrawal of minoxidil. Rechallenge was positive once in one patient and twice in another. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2256586", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 814, "text": "During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-5 beats min-1. Compared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2). We conclude that in healthy subjects short-term use of topical minoxidil is likely not to be detrimental. However, safety needs to be established regarding ischaemic symptoms in patients with coronary artery disease as well as for the possible development of LV hypertrophy in healthy subjects during years of therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3191000", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 631, "text": "The most frequently reported adverse reactions are mild scalp dryness and irritation and, rarely, allergic contact dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3311578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 763, "text": "Eight deaths that occurred during Upjohn-sponsored clinical trials of topical minoxidil and two deaths in subjects who used extemporaneous formulations of the drug are summarized. Of the eight patients in clinical trials, five had cardiovascular abnormalities and two had acquired immunodeficiency syndrome-related pneumonia. One patient died of a self-inflicted gunshot wound. One of the subjects who was using extemporaneous topical minoxidil had hypertension and arteriosclerotic disease and the other died of a myocardial infarction. There is little likelihood of significant adverse effects attributable to topical minoxidil because of its low systemic absorption. The evidence suggests that these deaths were the result of causes other than use of the drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3549808", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 702, "text": "Only 2% of prescribers reported complications other than local irritation that they associated with topical minoxidil therapy, but underreporting of noncutaneous side effects in this survey of dermatologists cannot be excluded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3800424", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 777, "text": "Typical side effects of this topical treatment include irritative dermatitis going along with pruritus, erythema, scaling and dryness, which occur especially at the onset of the therapy. In some cases, allergic contact dermatitis or exacerbation of seborrheic dermatitis has been reported. While most of the patients with allergic contact dermatitis described in the literature showed a positive sensitization to the vehicle substance propylene glycol evaluated by patch testing, reactions to the active ingredient minoxidil are rare", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15982234", "endSection": "abstract" } ] }, { "body": "Is arimoclomol a co-inducer of the heat shock response?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22591194", "http://www.ncbi.nlm.nih.gov/pubmed/18551622", "http://www.ncbi.nlm.nih.gov/pubmed/20582873", "http://www.ncbi.nlm.nih.gov/pubmed/19183864", "http://www.ncbi.nlm.nih.gov/pubmed/17656567", "http://www.ncbi.nlm.nih.gov/pubmed/24853414", "http://www.ncbi.nlm.nih.gov/pubmed/23978556", "http://www.ncbi.nlm.nih.gov/pubmed/18673445", "http://www.ncbi.nlm.nih.gov/pubmed/19938902", "http://www.ncbi.nlm.nih.gov/pubmed/23393146" ], "ideal_answer": [ "Yes, arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress." ], "exact_answer": "yes", "type": "yesno", "id": "56f7d9dd09dd18d46b000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23978556", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 805, "text": "In this review we summarize the evidence for the neuroprotective effects of enhanced heat shock protein expression by Arimoclomol and other inducers of the Heat Shock Response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23978556", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1121, "text": "arimoclomol, a co-inducer of the heat shock stress response,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393146", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1440, "text": "The heat-shock response (HSR) was activated in P23H retinae, and this was enhanced with arimoclomol treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24853414", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 246, "text": " We also assessed these functions in mice treated with a known heat shock protein inducer, arimoclomol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22591194", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 897, "text": " Under conditions of excessive stress, arimoclomol induces amplification of the cytoprotective heat shock response in order to protect motor neurons from death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582873", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 487, "text": "Although both arimoclomol and celastrol induced the expression of Hsp70", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19183864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Arimoclomol, an amplifier of heat shock protein expression involved in cellular stress response, has emerged as a potential therapeutic candidate in amyotrophic lateral sclerosis (ALS) in recent years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19938902", "endSection": "abstract" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1485, "text": "The mechanism of action of arimoclomol involves potentiation of the heat shock response, and treatment with arimoclomol increased Hsp70 expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18673445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18551622", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 554, "text": "Arimoclomol, a coinducer of heat shock proteins, delayed progression of amyotrophic lateral sclerosis (ALS) in a mouse model in which motor neurons in the spinal cord and motor cortex degenerate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17656567", "endSection": "abstract" } ] }, { "body": "What memory problems are reported in the \" Gulf war syndrome\"", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15251045", "http://www.ncbi.nlm.nih.gov/pubmed/11600803", "http://www.ncbi.nlm.nih.gov/pubmed/9005271", "http://www.ncbi.nlm.nih.gov/pubmed/14515407", "http://www.ncbi.nlm.nih.gov/pubmed/9096828", "http://www.ncbi.nlm.nih.gov/pubmed/11478226" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:4491", "o": "UMLS_CUI:C0282550" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:4491", "o": "persian gulf syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:4491", "o": "Gulf war syndrome (disorder)" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:4491", "o": "SNOMEDCT_2010_1_31:95877004" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:4491", "o": "MSH2010_2010_02_22:D018923" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1393478", "o": "0000013450" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0681713", "o": "http://linkedlifedata.com/resource/umls/label/A1393478" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1393478", "o": "Persian Gulf War period" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0681713", "o": "http://linkedlifedata.com/resource/umls/label/A1393478" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:4491", "o": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:3231" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:3231", "o": "occupational disease" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:3231", "o": "Occupational disorder (disorder)" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:3231", "o": "occupational disorder" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://data.linkedct.org/resource/condition/5434", "o": "http://dbpedia.org/resource/Gulf_War_syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://data.linkedct.org/resource/condition/5434", "o": "http://yago.org/resource/Gulf_War_syndrome" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/condition/5434", "o": "Condition #5434 (Gulf War Syndrome)" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_name", "s": "http://data.linkedct.org/resource/condition/5434", "o": "Gulf War Syndrome" } ], "ideal_answer": [ "memory loss" ], "exact_answer": [ "memory loss" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018923" ], "type": "factoid", "id": "52f896d62059c6d71c000046", "snippets": [ { "offsetInBeginSection": 1309, "offsetInEndSection": 1320, "text": "memory loss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15251045", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 902, "text": "loss of memory,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14515407", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 184, "text": " loss of memory", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11600803", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 401, "text": "dysmnesia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11478226", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1307, "text": "memory problems", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9096828", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1204, "text": "\"impaired cognition,\" characterized by problems with attention, memory, and reasoning, as well as insomnia, depression, daytime sleepiness, and headaches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9005271", "endSection": "abstract" } ] }, { "body": "Describe Heyde syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10441816", "http://www.ncbi.nlm.nih.gov/pubmed/23692692", "http://www.ncbi.nlm.nih.gov/pubmed/15764876", "http://www.ncbi.nlm.nih.gov/pubmed/17299265", "http://www.ncbi.nlm.nih.gov/pubmed/21864855", "http://www.ncbi.nlm.nih.gov/pubmed/11957793", "http://www.ncbi.nlm.nih.gov/pubmed/12912718", "http://www.ncbi.nlm.nih.gov/pubmed/19276092", "http://www.ncbi.nlm.nih.gov/pubmed/20545255", "http://www.ncbi.nlm.nih.gov/pubmed/20802419", "http://www.ncbi.nlm.nih.gov/pubmed/23605838", "http://www.ncbi.nlm.nih.gov/pubmed/17357954", "http://www.ncbi.nlm.nih.gov/pubmed/24008540", "http://www.ncbi.nlm.nih.gov/pubmed/25208564", "http://www.ncbi.nlm.nih.gov/pubmed/15568613", "http://www.ncbi.nlm.nih.gov/pubmed/25935884", "http://www.ncbi.nlm.nih.gov/pubmed/8470439", "http://www.ncbi.nlm.nih.gov/pubmed/25251907", "http://www.ncbi.nlm.nih.gov/pubmed/25367238" ], "ideal_answer": [ "Classical Heyde syndrome is described as the association of aortic stenosis, bleeding gastrointestinal angiodysplasia and secondary anemia. A deficiency of high molecular weight multimers of von Willebrand factor (type 2A von Willebrand disease) provides the link between this association." ], "type": "summary", "id": "56be14c7ef6e39474100000a", "snippets": [ { "offsetInBeginSection": 129, "offsetInEndSection": 232, "text": "The association of AVS and gastrointestinal bleeding from angiodysplasia is defined as Heyde syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25935884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Heyde syndrome is a triad of aortic stenosis, acquired coagulopathy, and anemia due to bleeding from intestinal angiodysplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25367238", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1353, "text": "Nine patients reported clinically significant bleeding, and seven had intestinal angiodysplasia and transfusion-dependent gastrointestinal bleeding (Heyde syndrome), with the median number of transfusions required being 20 (IQR 10-33; range 4-50). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25251907", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 545, "text": "Classical Heyde syndrome is described as the association of aortic stenosis, bleeding gastrointestinal angiodysplasia and secondary anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24008540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Gastrointestinal bleeding and aortic stenosis (Heyde syndrome): the role of aortic valve replacement.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692692", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Heyde syndrome (the combination of iron deficiency anemia and aortic stenosis) has been a controversial entity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "OBJECTIVE: We sought to evaluate the effectiveness of aortic valve replacement for reducing gastrointestinal bleeding in patients with Heyde syndrome, in whom gastrointestinal bleeding is associated with intestinal angiodysplasia and aortic valve stenosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21864855", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 958, "text": "CONCLUSIONS: The relationship between aortic valve stenosis, acquired von Willebrand disease and gastrointestinal bleeding in elderly patients is known as Heyde syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20802419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Aortic valve stenosis can be complicated by gastrointestinal bleeding from angiodysplasia. A deficiency of high molecular weight multimers of von Willebrand factor (vWF) (type 2A von Willebrand disease) provides the link between this association, which is known as Heyde syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Heyde syndrome--the link between aortic stenosis and gastrointestinal bleeding.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20545255", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Heyde syndrome is a triad of aortic stenosis, an acquired coagulopathy and anaemia due to bleeding from intestinal angiodysplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "[Calcifying aortic valve stenosis and occult gastrointestinal hemorrhage (Heyde syndrome): description of 2 cases].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10441816", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Risk of recurrent gastrointestinal bleeding after aortic valve replacement in patients with Heyde syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21864855", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The Heyde syndrome consists of the association of gastrointestinal bleeding from angiodysplasia with aortic valve stenosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17299265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Heyde syndrome (the combination of iron deficiency anemia and aortic stenosis) has been a controversial entity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "The association between aortic valve stenosis and gastrointestinal bleeding, traditionally known as Heyde's syndrome, is the result of a quantitative loss of the highest molecular weight von Willebrand multimers (type 2A von Willebrand syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25208564", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1341, "text": "The pathophysiology of Heyde's syndrome: an acquired von Willebrand deficiency syndrome has a much wider impact than was commonly thought, both in terms of how common it is and in how the association may be extrapolated to a wide range of bleeding disorders, rather than simply angiodysplasia associated gastrointestinal haemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23605838", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 544, "text": "Classical Heyde syndrome is described as the association of aortic stenosis, bleeding gastrointestinal angiodysplasia and secondary anemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24008540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Heyde syndrome (the combination of iron deficiency anemia and aortic stenosis) has been a controversial entity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Gastrointestinal bleeding and aortic stenosis (Heyde syndrome): the role of aortic valve replacement", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23692692", "endSection": "title" }, { "offsetInBeginSection": 59, "offsetInEndSection": 355, "text": "Heyde syndrome describes the coincidence of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia. We describe one characteristic case of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia which subsided after replacement with an aortic valve bioprosthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17357954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The Heyde syndrome describes the coincidence of aortic valve stenosis and intestinal bleeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11957793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The Heyde syndrome describes the association between calcific aortic stenosis and intestinal bleeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15568613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The association between aortic stenosis and digestive angiodysplasia has been described for the first time by Heyde in 1958. This entity is thus known as Heyde's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8470439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Heyde syndrome is described as the association of arteriovenous malformations (AVMs) of the gastrointestinal tract and aortic stenosis (AS); its existence,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12912718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": " Angiodysplasia are common in patients over the age of 60. Heyde syndrome describes the coincidence of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17357954", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 374, "text": "There is a relationship between aortic valve stenosis and gastrointestinal bleeding in elderly patients, called Heyde syndrome. The described patient had chronic anemia that worsened after surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15764876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Angiodysplasia are common in patients over the age of 60. Heyde syndrome describes the coincidence of aortic valve stenosis and gastrointestinal bleeding from angiodysplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17357954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Heyde syndrome is a triad of aortic stenosis, acquired coagulopathy, and anemia due to bleeding from intestinal angiodysplasia. Here we describe a case of this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25367238", "endSection": "abstract" } ] }, { "body": "Has silicon been used in treatment of incontinence ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20065535", "http://www.ncbi.nlm.nih.gov/pubmed/9690182", "http://www.ncbi.nlm.nih.gov/pubmed/10711555", "http://www.ncbi.nlm.nih.gov/pubmed/15582258", "http://www.ncbi.nlm.nih.gov/pubmed/12806798", "http://www.ncbi.nlm.nih.gov/pubmed/15183554", "http://www.ncbi.nlm.nih.gov/pubmed/22687358", "http://www.ncbi.nlm.nih.gov/pubmed/22933007", "http://www.ncbi.nlm.nih.gov/pubmed/10838378" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012828", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012825", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014549" ], "type": "yesno", "id": "536172d17d100faa09000009", "snippets": [ { "offsetInBeginSection": 686, "offsetInEndSection": 1026, "text": "an artificial anal sphincter. Worldwide, there are two established devices on the market: the artificial bowel sphincter\u00ae (ABS) from A. M. S. (Minnetonka, MN, USA) and the soft anal band\u00ae from A. M. I. (Feldkirch, Austria). How to implant the artificial anal sphincter? Both devices consist of a silicon cuff which can be filled with fluid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22933007", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 326, "text": "The InVance\u2122 system uses a silicon-coated polyester sling positioned under the bulbar urethra via a perineal incision.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22687358", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 869, "text": "Through a perineal incision three titanium screws with a polipropylene suture were inserted in each ischiopubic rami, and a silicon/polipropylene mesh (Invance) is affixed to them, compressing the bulbar urethra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20065535", "endSection": "abstract" }, { "offsetInBeginSection": 65, "offsetInEndSection": 450, "text": "surgical treatment of female stress urinary incontinence with a trans-obturator sub-urethral tape of Uratape (Porg\u00e9s). METHODS: Treatment and follow up of their complication were performed at the CHRU of Lille. RESULTS: In both cases, this complication is related to prolonged vaginal exposition of the tape. Vaginal erosion always occurs next to the silicon coated section of the tape", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15582258", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 705, "text": "A non-elastic, polypropylene tape (UraTape, Mentor-Porg\u00e8s) with a silicon coated central part was placed under the mid-urethra.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15183554", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1767, "text": " Stress incontinence is a rare complication in men, usually following prostatic surgery. It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12806798", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 339, "text": "The Femassist is a medical-grade silicon dome-shaped device, worn over the urethra and held securely via suction and a commercially available adhesive lotion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10838378", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 142, "text": "To examine the performance of a silicon urinary control device for nonsurgical management of women with genuine stress incontinence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10711555", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 524, "text": "The \"FemAssist\" is a dome-shaped medical grade silicon device intended to be worn over the external urethral meatus and held in place by suction and an adhesive gel. Thirty eight women with varying degrees of genuine stress urinary incontinence (GSUI) or mixed incontinence on multichannel urodynamic testing were fitted with one of two sizes of \"FemAssist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9690182", "endSection": "abstract" } ] }, { "body": "Which proteins compose the error prevention GO (8-oxo-G) system in Pseudomonas putida?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17545288" ], "ideal_answer": [ "In P. putida (Pseudomonas putida) the error prevention GO (8-oxo-G) system is composed of MutY, MutM, and MutT enzymes." ], "exact_answer": [ [ "MutY" ], [ "MutM" ], [ "MutT" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044715", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044716" ], "type": "list", "id": "553fca6054168f6c79000002", "snippets": [ { "offsetInBeginSection": 637, "offsetInEndSection": 770, "text": "the GO repair enzymes MutY, MutM, and MutT are involved in the prevention of base substitution mutations in carbon-starved P. putida.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545288", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 770, "text": "Our results demonstrated that the GO repair enzymes MutY, MutM, and MutT are involved in the prevention of base substitution mutations in carbon-starved P. putida.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545288", "endSection": "abstract" } ] }, { "body": "List five applications of machine learning algorithms in medical diagnosis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22606669", "http://www.ncbi.nlm.nih.gov/pubmed/24321226", "http://www.ncbi.nlm.nih.gov/pubmed/21479187", "http://www.ncbi.nlm.nih.gov/pubmed/24263362", "http://www.ncbi.nlm.nih.gov/pubmed/16226240", "http://www.ncbi.nlm.nih.gov/pubmed/22606665", "http://www.ncbi.nlm.nih.gov/pubmed/24297560", "http://www.ncbi.nlm.nih.gov/pubmed/24286700", "http://www.ncbi.nlm.nih.gov/pubmed/24266942", "http://www.ncbi.nlm.nih.gov/pubmed/24290902", "http://www.ncbi.nlm.nih.gov/pubmed/23322959", "http://www.ncbi.nlm.nih.gov/pubmed/15788095", "http://www.ncbi.nlm.nih.gov/pubmed/23763826" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0730516", "o": "D001185" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0730516", "o": "Learning, Machine" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7786375", "o": "Machine Learning" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0376284", "o": "http://linkedlifedata.com/resource/umls/label/A0730516" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0376284", "o": "http://linkedlifedata.com/resource/umls/label/A7786375" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7786375", "o": "D001185" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0730516", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7786375", "o": "MeSH" }, { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://linkedlifedata.com/resource/semanticnetwork/id/T066", "o": "http://linkedlifedata.com/resource/semanticnetwork/id/T052" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/semanticnetwork/id/T066", "o": "Machine Activity" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/semanticnetwork/id/T052", "o": "Activity" } ], "ideal_answer": [ "Machine learning technology is well suited for the induction of diagnostic and prognostic rules and solving of small and specialized diagnostic and prognostic problems. The medical diagnostic knowledge can be automatically derived from the description of cases solved in the past. In several medical domains we actually applied machine learning algorithms. Typically, the automatically generated diagnostic rules achieved the same or slightly better diagnostic accuracy than physicians specialists. There many several application of machine learning algorithms in medical diagnosis such as Brain glioma progression, Microarray classification, Mass spectral proteomics, Lymph disease classification and Parkinson's disease." ], "exact_answer": [ [ "Brain glioma progression" ], [ "Microarray classification" ], [ "Mass spectral proteomics" ], [ "Lymph disease classification" ], [ "Parkinson's disease" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003933", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011337", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000465", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007858", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001185" ], "type": "list", "id": "52ee065d98d0239505000033", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 160, "text": "The ability to differentiate between brain tumor progression and radiation therapy induced necrosis is critical for appropriate patient management. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321226", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 947, "text": "Experimental results on public leukemia, prostate, and colon cancer datasets show that fuzzy support vector machine applied in combination with filter or wrapper feature selection methods develops a robust model with higher accuracy than the conventional microarray classification models such as support vector machine, artificial neural network, decision trees, k nearest neighbors, and diagonal linear discriminant analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24266942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 614, "text": "Mass spectrometry based proteomics technologies have allowed for a great progress in identifying disease biomarkers for clinical diagnosis and prognosis. However, they face acute challenges from a data reproducibility standpoint, in that no two independent studies have been found to produce the same proteomic patterns. Such reproducibility issues cause the identified biomarker patterns to lose repeatability and prevent real clinical usage. In this work, we propose a profile biomarker approach to overcome this problem from a machine-learning viewpoint by developing a novel derivative component analysis (DCA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297560", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 517, "text": "In this paper, a random forest classifier (RFC) approach is proposed to diagnose lymph diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24290902", "endSection": "abstract" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1758, "text": "The algorithm provides excellent discrimination of PD patients from PSP patients at an individual level, thus encouraging the application of computer-based diagnosis in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24286700", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 430, "text": "The objective of this project was the development and validation of a multiparameter machine learning algorithm and system capable of predicting the need for life-saving interventions (LSIs) in trauma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24263362", "endSection": "abstract" } ] }, { "body": "Does the 3D structure of the genome remain stable during cell differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25693564", "http://www.ncbi.nlm.nih.gov/pubmed/26340639", "http://www.ncbi.nlm.nih.gov/pubmed/24346698", "http://www.ncbi.nlm.nih.gov/pubmed/25218583", "http://www.ncbi.nlm.nih.gov/pubmed/22495300", "http://www.ncbi.nlm.nih.gov/pubmed/23199754", "http://www.ncbi.nlm.nih.gov/pubmed/24905166", "http://www.ncbi.nlm.nih.gov/pubmed/25479748", "http://www.ncbi.nlm.nih.gov/pubmed/24305663" ], "ideal_answer": [ "Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation. The open chromatin of embryonic stem cells (ESCs) condenses into repressive heterochromatin as cells exit the pluripotent state. The relation between alterations in chromatin structure and changes in gene expression during cell differentiation has served as a paradigm to understand the link between genome organization and function. Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation. Architectural proteins orchestrate higher-order chromatin organization through the establishment of interactions between regulatory elements across multiple spatial scales. The regulation of these proteins, their interaction with DNA, and their co-occurrence in the genome, may be responsible for the plasticity of 3D chromatin architecture that dictates cell and time-specific blueprints of gene expression.", "Chromatin insulators have emerged as one of the central components of the genome organization tool-kit across species. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0030154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002454" ], "type": "yesno", "id": "56ebfac12ac5ed1459000001", "snippets": [ { "offsetInBeginSection": 940, "offsetInEndSection": 1109, "text": "We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495300", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1376, "text": "The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495300", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 733, "text": "Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26340639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The relation between alterations in chromatin structure and changes in gene expression during cell differentiation has served as a paradigm to understand the link between genome organization and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218583", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 929, "text": "Architectural proteins orchestrate higher-order chromatin organization through the establishment of interactions between regulatory elements across multiple spatial scales. The regulation of these proteins, their interaction with DNA, and their co-occurrence in the genome, may be responsible for the plasticity of 3D chromatin architecture that dictates cell and time-specific blueprints of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218583", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 430, "text": "The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24346698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24346698", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 666, "text": "Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24346698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24305663", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 908, "text": "Moreover, we reveal that formation of such highly condensed, transcriptionally repressed heterochromatin promotes transcriptional activation of differentiation genes and loss of pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479748", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The open chromatin of embryonic stem cells (ESCs) condenses into repressive heterochromatin as cells exit the pluripotent state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479748", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 715, "text": "we find that localized heterochromatin condensation of ribosomal RNA genes initiates establishment of highly condensed chromatin structures outside of the nucleolus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479748", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 676, "text": "We focus on the emerging relationship between genome organization and lineage-specific transcriptional regulation, which we argue are inextricably linked.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Cells face the challenge of storing two meters of DNA in the three-dimensional (3D) space of the nucleus that spans only a few microns. The nuclear organization that is required to overcome this challenge must allow for the accessibility of the gene regulatory machinery to the DNA and, in the case of embryonic stem cells (ESCs), for the transcriptional and epigenetic changes that accompany differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23199754", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 1076, "text": "In this review we summarize some of the recent findings illuminating the 3D structure of the eukaryotic genome, as well as the relationship between genome topology and function from the level of whole chromosomes to enhancer-promoter loops with a focus on features affecting genome organization in ESCs and changes in nuclear organization during differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23199754", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 742, "text": "We observe that although self-associating chromatin domains are stable during differentiation, chromatin interactions both within and between domains change in a striking manner, altering 36% of active and inactive chromosomal compartments throughout the genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25693564", "endSection": "abstract" } ] }, { "body": "What is the main biological function of the CRISPR-CAS9 genome editing system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23918387", "http://www.ncbi.nlm.nih.gov/pubmed/24179142", "http://www.ncbi.nlm.nih.gov/pubmed/24257628", "http://www.ncbi.nlm.nih.gov/pubmed/23827738", "http://www.ncbi.nlm.nih.gov/pubmed/24088745", "http://www.ncbi.nlm.nih.gov/pubmed/24199189", "http://www.ncbi.nlm.nih.gov/pubmed/24141137", "http://www.ncbi.nlm.nih.gov/pubmed/24326186", "http://www.ncbi.nlm.nih.gov/pubmed/23643243" ], "ideal_answer": [ "The CRISPR/Cas9 system (clustered regularly interspaced short palindromic repeats/CRISPR-associated) has recently emerged as an efficient and simple tool for site-specific engineering of eukaryotic genomes. The CRISPR/Cas9 system has attracted significant attention for its potential to transform genome engineering. It has been shown that the RNA-guided Cas9 nuclease can be employed to engineer the Drosophila genome, and that these modifications are efficiently transmitted through the germline. The CRISPR/Cas9 system has been reported to efficiently induce targeted gene disruption and homologous recombination in both prokaryotic and eukaryotic cells. The CRISPR/Cas9 system has been used to create knock-out alleles with great efficiency, and it has also been employed in knock-in of DNA cassettes at defined loci via homologous recombination (HR). The ease and efficiency of the CRISPR/Cas9 system with limited off-target effects make it a powerful genome engineering tool for in vivo studies." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064113", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064112" ], "type": "summary", "id": "54fc58df6ea36a810c000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Mutagenesis and homologous recombination in Drosophila cell lines using CRISPR/Cas9.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24326186", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 494, "text": "We have applied the CRISPR/Cas9 system to Drosophila S2 cells to generate targeted genetic mutations in more than 85% of alleles. By targeting a constitutive exon of the AGO1 gene, we demonstrate homozygous mutation in up to 82% of cells, thereby allowing the study of genetic knockouts in a Drosophila cell line for the first time. We have shown that homologous gene targeting is possible at 1-4% efficiency using this system, allowing for the construction of defined insertions and deletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24326186", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 833, "text": "This technology enables controlled genetic manipulation in Drosophila cell lines, and its simplicity offers the opportunity to study cellular phenotypes genome-wide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24326186", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 238, "text": "The prokaryotic CRISPR/Cas9 type II genome editing system has recently been applied in cell lines and vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257628", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 705, "text": "We now demonstrate that CRISPR/Cas9 mutagenesis in zebrafish is highly efficient, reaching up to 86.0%, and is heritable. The efficiency of the CRISPR/Cas9 system further facilitated the targeted knock-in of a protein tag provided by a donor oligonucleotide with knock-in efficiencies of 3.5-15.6%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257628", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 971, "text": "The ease and efficiency of the CRISPR/Cas9 system with limited off-target effects make it a powerful genome engineering tool for in vivo studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24257628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Cas9/CRISPR has been reported to efficiently induce targeted gene disruption and homologous recombination in both prokaryotic and eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24199189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 550, "text": "Sequence-specific nucleases like TALENs and the CRISPR/Cas9 system have greatly expanded the genome editing possibilities in model organisms such as zebrafish. Both systems have recently been used to create knock-out alleles with great efficiency, and TALENs have also been successfully employed in knock-in of DNA cassettes at defined loci via homologous recombination (HR). Here we report CRISPR/Cas9-mediated knock-in of DNA cassettes into the zebrafish genome at a very high rate by homology-independent double-strand break (DSB) repair pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24179142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The type II CRISPR/Cas9 system (clustered regularly interspaced short palindromic repeats/CRISPR-associated) has recently emerged as an efficient and simple tool for site-specific engineering of eukaryotic genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "The CRISPR/Cas9 system has attracted significant attention for its potential to transform genome engineering. We and others have recently shown that the RNA-guided Cas9 nuclease can be employed to engineer the Drosophila genome, and that these modifications are efficiently transmitted through the germline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24088745", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1250, "text": "Here we highlight the variety of genome modifications facilitated by the CRISPR/Cas9 system along with key considerations for starting your own CRISPR genome engineering project.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24088745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Here, we present a simple and highly efficient method for generating and detecting mutations of\u00a0any gene in Drosophila melanogaster through the\u00a0use of the CRISPR/Cas9 system (clustered regularly\u00a0interspaced palindromic repeats/CRISPR-associated).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23827738", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 557, "text": "Recently the type II prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system has been adapted to serve as a targeted genome mutagenesis tool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918387", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1415, "text": "This CRISPR/Cas9 system represents a highly effective and scalable gene knockout method in zebrafish and has the potential for applications in other model organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918387", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 321, "text": "The CRISPR/Cas system has been adapted as an efficient gene-targeting technology with the potential for multiplexed genome editing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23643243", "endSection": "abstract" } ] }, { "body": "Does dronedarone affect T3 and T4 levels?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17391666", "http://www.ncbi.nlm.nih.gov/pubmed/8640331", "http://www.ncbi.nlm.nih.gov/pubmed/12063079" ], "ideal_answer": [ "NO." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.biosemantics.org/jochem#4275389", "http://www.biosemantics.org/jochem#4274245", "http://www.biosemantics.org/jochem#4005955", "http://www.biosemantics.org/jochem#4233556" ], "type": "yesno", "id": "516d4b27298dcd4e51000077", "snippets": [ { "offsetInBeginSection": 793, "offsetInEndSection": 925, "text": "Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12063079", "endSection": "sections.0" }, { "offsetInBeginSection": 179, "offsetInEndSection": 342, "text": "Fifty-five Wistar rats were randomly allocated to a 2-week oral treatment with either vehicle (n=18), amiodarone (30 mg/kg, n=20), or dronedarone (30 mg/kg, n=17).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17391666", "endSection": "sections.0" }, { "offsetInBeginSection": 756, "offsetInEndSection": 801, "text": "Thyroid function was similar in the 3 groups.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17391666", "endSection": "sections.0" }, { "offsetInBeginSection": 1849, "offsetInEndSection": 2070, "text": "Plasma levels of T3, T4, and rT3 were changed after SR 33589 treatment except a decrease in T4 level at the highest dose whilst the T4 T3 ratio and the level of rT3 were dose-dependently increased by amiodarone treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8640331", "endSection": "sections.0" } ] }, { "body": "What is 2d 4d ratio in athletes.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23444944", "http://www.ncbi.nlm.nih.gov/pubmed/19954495", "http://www.ncbi.nlm.nih.gov/pubmed/20981610", "http://www.ncbi.nlm.nih.gov/pubmed/25520769", "http://www.ncbi.nlm.nih.gov/pubmed/24949031", "http://www.ncbi.nlm.nih.gov/pubmed/22185395", "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "http://www.ncbi.nlm.nih.gov/pubmed/20733526", "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "http://www.ncbi.nlm.nih.gov/pubmed/21993037", "http://www.ncbi.nlm.nih.gov/pubmed/16254897" ], "ideal_answer": [ "Lower 2D:4D ratio was reported to be lower in handball players, kabaddi players, varsity athletes, football players, soccer players and rugby players. Low 2D:4D ratio correlates with better performance and with enhanced sporting prowess, particularly with regard to activities requiring endurance and dependent upon slow-twitch muscles." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ], "type": "summary", "id": "56bf4035ef6e394741000010", "snippets": [ { "offsetInBeginSection": 756, "offsetInEndSection": 1015, "text": "RESULTS: A highly significant difference was found in 2D:4D ratios of both the hands with Kabaddi players having a lower ratio compared to their controls. There was no statistically significant difference in 2D:4D (\u0394 r-l) between Kabaddi players and controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25520769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "BACKGROUND: Ratio of second and fourth digit (2D:4D) is known to be germane in analyzing utero concentrations of testosterone and estrogen in human and other vertebrates. 2D:4D had been linked to several traits like athletes' abilities, reproductive success, risk of cancer and cardiovascular disease (CVD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24949031", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 857, "text": "There was also a lower digit ratio in both females and males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444944", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 489, "text": "Research from other fields is presented to suggest that healthy individuals with low 2D:4D ratio have enhanced sporting prowess, particularly with regard to activities requiring endurance and dependent upon slow-twitch muscles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185395", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Varsity athletes have lower 2D:4D ratios than other university students.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "title" }, { "offsetInBeginSection": 283, "offsetInEndSection": 405, "text": "The 2D:4D ratio has been negatively correlated with many factors, including aggression, physical fitness, and athleticism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 1100, "text": "Our results confirmed that both male (mean \u00b1 s(x) : 0.97 \u00b1 0.004) and female (0.98 \u00b1 0.005) varsity athletes had significantly lower ratios than their non-varsity peers (males: 0.99 \u00b1 0.004; females: 1.00 \u00b1 0.006), and that male athletes had significantly lower 2D:4D ratios than female athletes. Overall, males had significantly lower 2D:4D ratios than females (0.98 \u00b1 0.003 vs. 0.99 \u00b1 0.004). A smaller 2D:4D ratio appears to be consistent with participation in varsity sports among both males and females.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "Research suggests that prenatal levels of testosterone are related to finger length development and traits beneficial to athletic skill, such as power, endurance, visual-spatial skills, or sensation seeking and dominance behavior. In men, the second digit to fourth digit ratio (2D:4D) has been shown to correlate with success in competitive levels of football (soccer), which suggests that the 2D:4D ratio is a possible marker for level of attainment in sport. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20733526", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1456, "text": "Significant differences were found among the different groups (p = 0.000), with significantly lower ratios between football and crew (p = 0.000), football and nonathletes (p = 0.030), and gymnastics and crew (p = 0.001). This research provides a stronger level of evidence that the 2D:4D ratio may help indicate potential athleticism or competition-level achievement, but the external validity may be limited to only specific sports.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20733526", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 271, "text": "Low 2D:4D has been linked to various measures of performance in a range of sports (e.g., soccer, rugby). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993037", "endSection": "abstract" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1295, "text": "We found that right 2D:4D (but not left 2D:4D or right-left 2D:4D) was significantly negatively correlated with coaches' ratings (r(s) = 0.58) and the competition result (r(s) = 0.30). It appears that in line with other sports that low right 2D:4D (high prenatal testosterone and low prenatal estrogen) correlates to high surfing ability in men.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993037", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 1085, "text": "Compared with controls, players were larger and had lower 2D:4D for the right and left hand. With regard to number of caps, players with low 2D:4D in their right hand and low right 2D:4D compared with their left (right\u00a0-\u00a0left 2D:4D difference) had high numbers of caps. First-choice players did not differ significantly from second-choice players in their 2D:4D but they did have a lower right\u00a0-\u00a0left 2D:4D difference than second-choice players. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981610", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1306, "text": "We conclude that low right 2D:4D and low right\u00a0-\u00a0left 2D:4D difference are predictors of high rugby performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Second-to-fourth digit ratio (2D:4D), a widely studied putative marker for masculinization through prenatal androgen exposure, is lower (more masculinized) in athletes than in general population controls, and athletes with lower 2D:4D have higher sporting success.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19954495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Digit ratio (2D:4D) predicts sporting success among female fencers independent from physical, experience, and personality factors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Research particularly focusing on male athletes and popular sports (running and soccer) suggests associations of lower (masculinized) second-to-fourth digit ratio (2D:4D), a putative marker of prenatal androgen action, with better sports performance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 807, "text": "Among female, but not male, fencers, lower 2D:4D was related to better national fencing rankings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1269, "text": "Athletes active in the most aggressive form (the sabre) had lower 2D:4D than those active in the other forms (\u00e9p\u00e9e and foil fencing).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1273, "text": "Our results showed that elite female athletes have significantly lower left hand 2D:4D ratios compared to the control group (P<0.05). Therefore, we can speculate that low 2D:4D ratio may be a positive correlate of sports potential in females.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254897", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1180, "text": "Our results confirmed that both male (mean \u00b1 s(x) : 0.97 \u00b1 0.004) and female (0.98 \u00b1 0.005) varsity athletes had significantly lower ratios than their non-varsity peers (males: 0.99 \u00b1 0.004; females: 1.00 \u00b1 0.006), and that male athletes had significantly lower 2D:4D ratios than female athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 888, "text": "Our results confirmed that both male (mean \u00b1 s(x) : 0.97 \u00b1 0.004) and female (0.98 \u00b1 0.005) varsity athletes had significantly lower ratios than their non-varsity peers (males: 0.99 \u00b1 0.004; females: 1.00 \u00b1 0.006), and that male athletes had significantly lower 2D:4D ratios than female athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 889, "text": "We compared 2D:4D finger ratios of (1) male and female varsity athletes (n = 99) versus male and female student non-athletes (n = 122), and (2) males (n = 104) versus females (n = 117). Our results confirmed that both male (mean \u00b1 s(x) : 0.97 \u00b1 0.004) and female (0.98 \u00b1 0.005) varsity athletes had significantly lower ratios than their non-varsity peers (males: 0.99 \u00b1 0.004; females: 1.00 \u00b1 0.006), and that male athletes had significantly lower 2D:4D ratios than female athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 972, "text": "Our results confirmed that both male (mean \u00b1 s(x) : 0.97 \u00b1 0.004) and female (0.98 \u00b1 0.005) varsity athletes had significantly lower ratios than their non-varsity peers (males: 0.99 \u00b1 0.004; females: 1.00 \u00b1 0.006), and that male athletes had significantly lower 2D:4D ratios than female athletes. Overall, males had significantly lower 2D:4D ratios than females (0.98 \u00b1 0.003 vs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1170, "text": "We measured the 2D:4D ratios in elite and non-elite female athletes and compared them with female individuals not engaged in any sport activities. Our results showed that elite female athletes have significantly lower left hand 2D:4D ratios compared to the control group (P < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254897", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 889, "text": "Our results confirmed that both male (mean \u00b1 s(x) : 0.97 \u00b1 0.004) and female (0.98 \u00b1 0.005) varsity athletes had significantly lower ratios than their non-varsity peers (males: 0.99 \u00b1 0.004; females: 1.00 \u00b1 0.006), and that male athletes had significantly lower 2D:4D ratios than female athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Second-to-fourth digit ratio (2D:4D), a widely studied putative marker for masculinization through prenatal androgen exposure, is lower (more masculinized) in athletes than in general population controls, and athletes with lower 2D:4D have higher sporting success.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19954495", "endSection": "abstract" } ] }, { "body": "What is the association between moon cycle and rupture risk of intracranial aneurysms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18353534" ], "ideal_answer": [ "The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001019", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000783", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002538", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002532", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016081", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017542" ], "type": "summary", "id": "52fc94932059c6d71c000072", "snippets": [ { "offsetInBeginSection": 380, "offsetInEndSection": 519, "text": "An incidence peak for aneurysm rupture (28 patients) was seen during the phase of new moon, which was statistically significant (p < 0.001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18353534", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 763, "text": "The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18353534", "endSection": "abstract" } ] }, { "body": "What is the role of brain natriuretic peptide in traumatic brain injury patients ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23963125", "http://www.ncbi.nlm.nih.gov/pubmed/20068481", "http://www.ncbi.nlm.nih.gov/pubmed/16774478", "http://www.ncbi.nlm.nih.gov/pubmed/18325424", "http://www.ncbi.nlm.nih.gov/pubmed/21808206", "http://www.ncbi.nlm.nih.gov/pubmed/19803787", "http://www.ncbi.nlm.nih.gov/pubmed/16322908", "http://www.ncbi.nlm.nih.gov/pubmed/17690842" ], "ideal_answer": [ "Brain natriuretic peptide concentrations are elevated in patients with traumatic brain during the acute phase and correlate with poor outcomes. In traumatic brain injury patients higher brain natriuretic peptide concentrations are associated with more extensive SAH, elevated ICP and hyponatremia. Brain natriuretic peptide may play an adaptive role in recovery through augmentation of cerebral blood flow." ], "concepts": [ "http://www.uniprot.org/uniprot/ANFB_ACITR", "http://www.uniprot.org/uniprot/ANFB_OREMO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001930", "http://www.biosemantics.org/jochem#4250398", "http://www.uniprot.org/uniprot/ANFB_TAKRU", "http://www.uniprot.org/uniprot/ANFB_MOUSE", "http://www.biosemantics.org/jochem#4264708", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020097" ], "type": "summary", "id": "5314d05adae131f84700000d", "snippets": [ { "offsetInBeginSection": 1301, "offsetInEndSection": 1613, "text": "This study provides evidence that BNP plasma concentrations increase rapidly after TBI. Plasma BNP concentrations are correlated with hyponatremia in severe TBI patients but not in mild and moderate TBI patients. Furthermore, patients with elevated ICP have a higher serum BNP level in first 4 days after injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21808206", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 1288, "text": "In average, the peak of BNP level was measured at 703.9 pg/mL\u00b1179.1 pg/mL on day 3 after injury, which was correlated to the severity of TBI. Among patients with severe TBI, plasma NT-proBNP concentrations in patients with hyponatremia were statistically higher than those without hyponatremia (p<0.05). In the hyponatremic group, the plasma NT-proBNP increased to a peak of 1001.16 pg/mL\u00b1131.52 pg/mL within 48 hours after injury and maintained at a high level for 3 days. In the normonatremic group, the plasma NT-proBNP reached a peak of 826.43 pg/mL\u00b1337.43 pg/mL on day 5 and quickly decreased thereafter. In addition, we found plasma NT-proBNP concentrations in patients with ICP>15 mm Hg were significantly higher than those in patients with ICP\u226415 mm Hg (p<0.01). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21808206", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "There is emerging evidence to suggest that brain natriuretic peptide (BNP) is elevated after acute brain injury, and that it may play an adaptive role in recovery through augmentation of cerebral blood flow (CBF). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19803787", "endSection": "abstract" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1750, "text": "hBNP improves neurological function in murine models of TBI and ICH, and was associated with enhanced CBF and downregulation of neuroinflammatory responses. hBNP may represent a novel therapeutic strategy after acute CNS injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19803787", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 508, "text": "Here, we describe 2 cases of CSW in TBI patients with elevated BNP levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18325424", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1058, "text": "These patients with TBI had findings consistent with CSW with elevated BNP levels in the setting of normal cardiac function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18325424", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 842, "text": "We measured NT-proBNP levels in cerebrospinal fluid (CSF) and serum of 14 patients suffering from severe TBI (GCS15 mm Hg (n=6), the serum (800+/-150 pg/mL) and CSF levels (55+/-9 pg/mL) of NT-proBNP were significantly increased after 24 h, as compared to patients with ICP15 mm Hg. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16774478", "endSection": "abstract" }, { "offsetInBeginSection": 1425, "offsetInEndSection": 1645, "text": "BNP plasma concentrations are elevated shortly after head injury and are continuously elevated during the acute phase in patients with more extensive SAH and in those with elevated ICP, and correlate with poor outcomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16322908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "BACKGROUND: According to the literature, serum beta-natriuretic peptide (BNP) levels have been shown to increase in adult trauma patients, specifically for those with traumatic brain injury and in those with intracranial hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20068481", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by Daratumumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25964097", "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "http://www.ncbi.nlm.nih.gov/pubmed/25531698", "http://www.ncbi.nlm.nih.gov/pubmed/24053207", "http://www.ncbi.nlm.nih.gov/pubmed/25626316", "http://www.ncbi.nlm.nih.gov/pubmed/21109694", "http://www.ncbi.nlm.nih.gov/pubmed/24555809", "http://www.ncbi.nlm.nih.gov/pubmed/24849305", "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "http://www.ncbi.nlm.nih.gov/pubmed/25988285", "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "http://www.ncbi.nlm.nih.gov/pubmed/25865943" ], "ideal_answer": [ "Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma.", "Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity." ], "exact_answer": [ "CD38" ], "type": "factoid", "id": "56c04412ef6e39474100001b", "snippets": [ { "offsetInBeginSection": 189, "offsetInEndSection": 357, "text": "Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25865943", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 489, "text": "Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 937, "text": "This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: Daratumumab (DARA), a promising novel therapy for multiple myeloma, is an IgG1\u03ba monoclonal antibody that recognizes CD38 on myeloma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1462, "text": "CONCLUSION: DARA causes panreactivity in vitro by binding to CD38 on reagent RBCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 496, "text": "Here, we describe that treatment of multiple myeloma patients with daratumumab, a novel anti-CD38 MoAb, resulted in false-positive indirect antiglobulin tests (IATs) for all patients for 2 to 6 months after infusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25988285", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 842, "text": "Interference of daratumumab and three other anti-CD38 MoAbs was studied using fresh-frozen plasma spiked with different MoAb concentrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25988285", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 356, "text": "Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25865943", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 490, "text": "Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 444, "text": "This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25626316", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 569, "text": "This is likely to change within the next few years with a number of mAb therapies being assessed in late stage clinical trials, most notably, the anti-CS-1 mAb, elotuzumab, and the anti-CD38 mAb, daratumumab, which are currently being evaluated in Phase III clinical trials for MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25964097", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 651, "text": "Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555809", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 230, "text": "Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "endSection": "title" }, { "offsetInBeginSection": 182, "offsetInEndSection": 538, "text": "In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 1047, "text": "Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells. Importantly, daratumumab-induced Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not affected by the presence of bone marrow stromal cells, indicating that daratumumab can effectively kill MM tumor cells in a tumor-preserving bone marrow microenvironment. In vivo, daratumumab was highly active and interrupted xenograft tumor growth at low dosing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 938, "text": "This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 678, "text": "elotuzumab which targets CS1 and daratumumab which targets CD38.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24053207", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 444, "text": "such as elotuzumab which targets CS1 and daratumumab which targets CD38.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25626316", "endSection": "abstract" }, { "offsetInBeginSection": 1821, "offsetInEndSection": 2034, "text": "Novel therapy strategies include targeted and stroma-directed approaches. Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24849305", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 653, "text": "an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555809", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 842, "text": "This review focuses on the basic and clinical aspects of two emerging and promising novel MoAbs for MM, elotuzumab which targets CS1 and daratumumab which targets CD38.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24053207", "endSection": "abstract" }, { "offsetInBeginSection": 2014, "offsetInEndSection": 2153, "text": "Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24849305", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 373, "text": "Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531698", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 793, "text": "Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555809", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1421, "text": "These findings support clinical development of daratumumab for the treatment of CD38-positive MM tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109694", "endSection": "title" }, { "offsetInBeginSection": 1888, "offsetInEndSection": 2027, "text": "Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24849305", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 337, "text": "In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 737, "text": "Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis. DESIGN AND METHODS: To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109694", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1324, "text": "These findings support clinical development of daratumumab for the treatment of CD38-positive MM tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 336, "text": "In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21187443", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 653, "text": "A novel therapeutic strategy that effectively targets specific molecules on myeloma cells and also potentially overcomes tumor microenvironment-mediated drug resistance and the downstream effects of genetic instability is thus urgently needed. Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555809", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 941, "text": "This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab. .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 232, "text": "an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531698", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 678, "text": "This review focuses on the basic and clinical aspects of two emerging and promising novel MoAbs for MM, elotuzumab which targets CS1 and daratumumab which targets CD38.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24053207", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 653, "text": "Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555809", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 232, "text": "Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA) has emerged as a breakthrough targeted therapy for patients with MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531698", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 444, "text": "This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25626316", "endSection": "abstract" }, { "offsetInBeginSection": 1895, "offsetInEndSection": 2034, "text": "Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24849305", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 357, "text": "Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25865943", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 599, "text": "We hypothesized that the observed panreactivity reflected DARA binding to CD38 on reagent RBCs, and we investigated methods to prevent this binding.STUDY DESIGN AND METHODS: DARA binding to CD38+ or CD38- HL60 cells was assessed by flow cytometry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1279, "text": "Flow cytometry experiments confirmed DARA binding to CD38+ HL60 cells, but not to CD38- controls. DTT treatment of CD38+ HL60 cells reduced DARA binding by 92% by denaturing cell surface CD38. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "endSection": "abstract" } ] }, { "body": "Which mutation is associated with PLMS (periodic limb movements in sleep)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19619967" ], "ideal_answer": [ "missense substitution, Met1Val (M1V), was identified in the DCX gene" ], "exact_answer": [ "missense substitution, Met1Val (M1V), in the DCX gene." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020189", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "factoid", "id": "52f899952059c6d71c00004b", "snippets": [ { "offsetInBeginSection": 541, "offsetInEndSection": 732, "text": "We describe a 2-year-old girl affected by SBH with epilepsy and periodic limb movements (PLMs), in whom a novel \"de novo\" missense substitution, Met1Val (M1V), was identified in the DCX gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19619967", "endSection": "abstract" } ] }, { "body": "Which DNA repair system is involved in HNPCC?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8723065", "http://www.ncbi.nlm.nih.gov/pubmed/21459714", "http://www.ncbi.nlm.nih.gov/pubmed/9244653" ], "ideal_answer": [ "In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development." ], "exact_answer": [ "In HNPCC, the mismatch DNA repair system is involved." ], "concepts": [ "http://www.uniprot.org/uniprot/MSH3_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://www.disease-ontology.org/api/metadata/DOID:3883", "http://www.uniprot.org/uniprot/MSH3_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045643", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032425", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032423", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006298", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053843", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006281", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032424", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006283", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006282" ], "type": "factoid", "id": "53161545b166e2b806000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "The HNPCC syndrome (hereditary non polyposis colon cancer) or Lynch syndrome stands for an autosomic dominant condition leading to the most prevalent hereditary colo-rectal cancers (CCR). MMR (mismatch repair)'s genes are involved in carcinogenesis as they play a role in ADNA mismatch repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21459714", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 1024, "text": "Mutations in the genes of the mismatch DNA repair system and of the TGF-beta-II-receptor, the main defects of the HNPCC (hereditary nonpolyposis colorectal cancer), are exclusively identified in sequences of microsatellites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9244653", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 666, "text": "In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8723065", "endSection": "abstract" } ] }, { "body": "Mention the only available genomics and developmental transcriptomics resource for the urochordate Oikopleura dioica", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23185044" ], "ideal_answer": [ "OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/) is a tiling array-based genome browser resource for Oikopleura dioica, a metazoan belonging to the urochordates, the closest extant group to vertebrates. OikoBase facilitates retrieval and mining of a variety of useful genomics information and will provide a valuable resource for research in chordate development, genome evolution and plasticity and the molecular ecology of this important marine planktonic organism." ], "exact_answer": [ "OikoBase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015509", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014561", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281" ], "type": "factoid", "id": "56ae6e650a360a5e4500000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "OikoBase: a genomics and developmental transcriptomics resource for the urochordate Oikopleura dioica.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185044", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1405, "text": "We report the development of OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/), a tiling array-based genome browser resource for Oikopleura dioica, a metazoan belonging to the urochordates, the closest extant group to vertebrates. OikoBase facilitates retrieval and mining of a variety of useful genomics information. First, it includes a genome browser which interrogates 1260 genomic sequence scaffolds and features gene, transcript and CDS annotation tracks. Second, we annotated gene models with gene ontology (GO) terms and InterPro domains which are directly accessible in the browser with links to their entries in the GO (http://www.geneontology.org/) and InterPro (http://www.ebi.ac.uk/interpro/) databases, and we provide transcript and peptide links for sequence downloads. Third, we introduce the transcriptomics of a comprehensive set of developmental stages of O. dioica at high resolution and provide downloadable gene expression data for all developmental stages. Fourth, we incorporate a BLAST tool to identify homologs of genes and proteins. Finally, we include a tutorial that describes how to use OikoBase as well as a link to detailed methods, explaining the data generation and analysis pipeline. OikoBase will provide a valuable resource for research in chordate development, genome evolution and plasticity and the molecular ecology of this important marine planktonic organism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "We report the development of OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/), a tiling array-based genome browser resource for Oikopleura dioica, a metazoan belonging to the urochordates, the closest extant group to vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "OikoBase: a genomics and developmental transcriptomics resource for the urochordate Oikopleura dioica", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185044", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "We report the development of OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/), a tiling array-based genome browser resource for Oikopleura dioica, a metazoan belonging to the urochordates, the closest extant group to vertebrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "We report the development of OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/), a tiling array-based genome browser resource for Oikopleura dioica, a metazoan belonging to the urochordates, the closest extant group to vertebrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23185044", "endSection": "abstract" } ] }, { "body": "What is the association between NT-proBNP and cognitive function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25142900", "http://www.ncbi.nlm.nih.gov/pubmed/22479261", "http://www.ncbi.nlm.nih.gov/pubmed/23579182", "http://www.ncbi.nlm.nih.gov/pubmed/24333505", "http://www.ncbi.nlm.nih.gov/pubmed/21526197", "http://www.ncbi.nlm.nih.gov/pubmed/22973461", "http://www.ncbi.nlm.nih.gov/pubmed/21683832", "http://www.ncbi.nlm.nih.gov/pubmed/24942833", "http://www.ncbi.nlm.nih.gov/pubmed/23384944", "http://www.ncbi.nlm.nih.gov/pubmed/20727348" ], "ideal_answer": [ "Greater NT-proBNP serum concentration is associated with poorer cognitive function and cognitive decline. In community-dwelling older adults, greater NT-proBNP levels were strongly associated with poor cognitive function independently from age, sex, education, hypertension, body mass index, exercise, alcohol use, smoking, low density lipoprotein cholesterol, creatinine clearance, and previous cardiovascular disease. However, other authors did not find an association between NT-proBNP and severe cognitive impairment (SCI)." ], "type": "summary", "id": "55032785e9bde69634000031", "snippets": [ { "offsetInBeginSection": 1027, "offsetInEndSection": 1175, "text": "RESULTS: Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23579182", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1185, "text": "SCI was present at baseline more often in NYHA IV patients compared with NYHA II [odds ratio 2.94; 95% confidence interval (CI) 1.15-7.51, P = 0.025], but it was not related to NT-proBNP levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23384944", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 2049, "text": "Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of 'g') and 'possible' depression (HADS depression \u22658) (OR 1.80; 95% CI: 1.20, 2.70; p\u200a=\u200a0.005 and OR 2.18; 95% CI: 1.28, 3.71; p\u200a=\u200a0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (\u03b2 -0.02, 95% CI -0.07 to 0.03, p>0.05 for 'g'; \u03b2 0.03, 95% CI -0.02 to 0.07, p>0.05 for depression scores). CONCLUSION: Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973461", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 711, "text": "RESULTS AND CONCLUSION: Patients with vascular disease and elevated serum NT-proBNP level had a lower cognition level, shorter survival time, lower renal function and a higher percentage of pathological brain imaging than patients with vascular disease and normal NT-proBNP level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22479261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "BACKGROUND: Natriuretic peptides have prognostic value across a wide spectrum of cardiovascular diseases and may predict cognitive dysfunction in patients with cardiovascular disease, even in the absence of previous stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21683832", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1711, "text": "In unadjusted analyses, all 3 cognitive function test scores were significantly associated with NT-proBNP levels (P<.001). After adjusting for age, sex, education, hypertension, body mass index, exercise, alcohol use, smoking, low density lipoprotein cholesterol, creatinine clearance, and previous cardiovascular disease, elevated NT-proBNP levels remained independently associated with poor cognitive performance on MMSE (odds ratio [OR] 2.0; 95% confidence interval [CI], 1.1-3.6; P=.02) and Trails B (OR 1.7; 95% CI, 1.2-2.7; P=.01), but not Category Fluency (OR 1.4; 95% CI, 0.9-2.2; P=.19). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21683832", "endSection": "abstract" }, { "offsetInBeginSection": 1798, "offsetInEndSection": 1936, "text": " CONCLUSIONS: NT-proBNP levels were strongly and independently associated with poor cognitive function in community-dwelling older adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21683832", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 876, "text": "However, NT-proBNP level did not predict cognition as assessed by MMSE score. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20727348", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 897, "text": "However, N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly enhanced both in MCI and AD patients (1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24333505", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1113, "text": "In a second analysis of a sample of 110 subjects including younger healthy controls, we confirmed that NT-proBNP has the potential to be a stable candidate protein for both diagnosis and AD disease progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24333505", "endSection": "abstract" }, { "offsetInBeginSection": 1585, "offsetInEndSection": 1708, "text": "Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22973461", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1207, "text": "In unadjusted analyses, all 3 cognitive function test scores were significantly associated with NT-proBNP levels (P<.001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21683832", "endSection": "abstract" }, { "offsetInBeginSection": 1772, "offsetInEndSection": 1896, "text": "NT-proBNP levels were strongly and independently associated with poor cognitive function in community-dwelling older adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21683832", "endSection": "abstract" } ] }, { "body": "List functional roles of the FtsZ protein.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23463171", "http://www.ncbi.nlm.nih.gov/pubmed/23384289", "http://www.ncbi.nlm.nih.gov/pubmed/24984796", "http://www.ncbi.nlm.nih.gov/pubmed/25124387", "http://www.ncbi.nlm.nih.gov/pubmed/25213228", "http://www.ncbi.nlm.nih.gov/pubmed/25382739", "http://www.ncbi.nlm.nih.gov/pubmed/24825009", "http://www.ncbi.nlm.nih.gov/pubmed/25002581", "http://www.ncbi.nlm.nih.gov/pubmed/25533961", "http://www.ncbi.nlm.nih.gov/pubmed/24506818", "http://www.ncbi.nlm.nih.gov/pubmed/24778116", "http://www.ncbi.nlm.nih.gov/pubmed/25519150", "http://www.ncbi.nlm.nih.gov/pubmed/24292151", "http://www.ncbi.nlm.nih.gov/pubmed/22932926", "http://www.ncbi.nlm.nih.gov/pubmed/24529242", "http://www.ncbi.nlm.nih.gov/pubmed/24502896" ], "ideal_answer": [ "Four major roles of FtsZ have been characterized: cell elongation, GTPase, cell division, and bacterial cytoskeleton." ], "exact_answer": [ [ "cell elongation" ], [ "GTPase" ], [ "cell division" ], [ "bacterial cytoskeleton" ] ], "concepts": [ "http://www.uniprot.org/uniprot/FTSZ_METTH", "http://www.uniprot.org/uniprot/FTSZ_MYCTU", "http://www.uniprot.org/uniprot/FTSZ_COXBU", "http://www.uniprot.org/uniprot/FTSZ_ECO57" ], "type": "list", "id": "56d094f33975bb303a000012", "snippets": [ { "offsetInBeginSection": 121, "offsetInEndSection": 217, "text": "bacterial homologue FtsZ establishes the cytokinetic ring that constricts during cell division. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "In Escherichia coli, initial assembly of the Z ring for cell division requires FtsZ plus the essential Z ring-associated proteins FtsA and ZipA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "FtsZ is an essential cell division protein in Escherichia coli, and its localization, filamentation, and bundling at the mid-cell are required for Z-ring stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25002581", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1194, "text": "the bacterial division FtsZ protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25124387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The GTPase-dependent polymerization/depolymerization dynamics of FtsZ regulate bacterial cell division in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24502896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Bacterial cytokinesis depends upon the tubulin-like GTPase FtsZ, which polymerizes into an annular structure at midcell (the Z-ring) that defines the division site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24529242", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 328, "text": "FtsZ is the first of the divisome proteins to accumulate at the division site and is widely thought to function as a force generator that constricts the cell envelope. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24506818", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 826, "text": "the cell division protein FtsZ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24778116", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 306, "text": "FtsZ, the key protein of bacterial cell division was selected as a potent anti bacterial target. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25519150", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 127, "text": "the cell-division protein FtsZ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292151", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 336, "text": " FtsZ and PG together function in orchestrating cell division and maintaining cell shape in almost all other bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24292151", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 138, "text": " the tubulin-like protein of the division septum FtsZ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23384289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "FtsZ is a widely distributed major cytoskeletal protein involved in the archaea and bacteria cell division. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22932926", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 336, "text": "Four major roles of FtsZ have been characterized: cell elongation, GTPase, cell division, and bacterial cytoskeleton. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22932926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Bacterial cell division involves a complex and dynamic sequence of events whereby polymers of the protein FtsZ assemble at the division plane and rearrange to achieve the goal of contracting the cell membrane at the site of cell division, thus dividing the parent cell into two daughter cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463171", "endSection": "abstract" }, { "offsetInBeginSection": 2249, "offsetInEndSection": 2279, "text": "the cell division protein FtsZ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825009", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 334, "text": "FtsZ, the homolog of eukaryotic tubulin, is a GTPase that assembles into cytokinetic Z rings essential for cell division in prokaryotic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24984796", "endSection": "abstract" } ] }, { "body": "Intetumumab has been tested in clinical trials for treatment of which cancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21750555", "http://www.ncbi.nlm.nih.gov/pubmed/23104724", "http://www.ncbi.nlm.nih.gov/pubmed/22027908", "http://www.ncbi.nlm.nih.gov/pubmed/20145975", "http://www.ncbi.nlm.nih.gov/pubmed/21331745" ], "ideal_answer": [ "Intetumumab has been tested in clinical trials for treatment of prostate cancer, melanoma and angiosarcoma." ], "exact_answer": [ [ "prostate cancer" ], [ "melanoma" ], [ "angiosarcoma" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430" ], "type": "list", "id": "550e866271445a662f000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human \u03b1\u03bd integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104724", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 476, "text": "BACKGROUND: Intetumumab is a fully human mAb with antiangiogenic, antitumor properties which has shown potential therapeutic effect in castration-resistant prostate cancer (CRPC) patients. PATIENTS AND METHODS: In a phase 2, randomized, double-blind, multicenter study, men with metastatic CRPC without prior systemic nonhormonal therapy were randomly assigned to 75-mg/m(2) docetaxel (Taxotere) and 5-mg prednisone plus placebo (N = 65) or 10-mg/kg intetumumab (N = 66) q3w. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104724", "endSection": "abstract" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1730, "text": "CONCLUSION: The addition of intetumumab to docetaxel resulted in shorter PFS without additional toxicity among CRPC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104724", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 491, "text": "Data from the Melanoma Subscale (MS) of the Functional Assessment of Cancer Therapy-Melanoma and the worst pain question from the Brief Pain Inventory (BPI) were taken from a clinical trial evaluating intetumumab alone or with dacarbazine in Stage IV metastatic melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "A randomised, phase II study of intetumumab, an anti-\u03b1v-integrin mAb, alone and with dacarbazine in stage IV melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750555", "endSection": "title" }, { "offsetInBeginSection": 1523, "offsetInEndSection": 1680, "text": "CONCLUSION: With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750555", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 446, "text": "METHODS: In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1:1:1:1 to 1000 mg m(-2) dacarbazine+placebo (n=32), 1000 mg m(-2) dacarbazine+10 mg kg(-1) intetumumab (n=32), 10 mg kg(-1) intetumumab (n=33), or 5 mg kg(-1) intetumumab (n=32) q3w. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Clinical and pharmacologic evaluation of two dose levels of intetumumab (CNTO 95) in patients with melanoma or angiosarcoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331745", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 559, "text": "PURPOSE: In this Phase 1, multicenter, open-label study, intetumumab (CNTO 95), a fully human anti-\u03b1v integrin monoclonal antibody was evaluated for safety, pharmacokinetics, and pharmacodynamic activity in patients with melanoma or angiosarcoma. PATIENTS AND METHODS: Patients with histologically-confirmed inoperable melanoma or angiosarcoma refractory to standard treatment were allocated to treatment with 10 mg/kg or 20 mg/kg intetumumab, administered once every 3 weeks for up to four cycles unless unacceptable toxicity or disease progression occurred.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331745", "endSection": "abstract" }, { "offsetInBeginSection": 1546, "offsetInEndSection": 1803, "text": "CONCLUSIONS: In patients with metastatic malignant melanoma and angiosarcoma in this study, intetumumab demonstrated manageable toxicity, was well tolerated, and presented approximately dose-proportional pharmacokinetics for the 10 mg/kg and 20 mg/kg doses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "A phase 1, multicenter, open-label study of the safety of two dose levels of a human monoclonal antibody to human \u03b1(v) integrins, intetumumab, in combination with docetaxel and prednisone in patients with castrate-resistant metastatic prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20145975", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "PURPOSE: We evaluated the safety and efficacy of intetumumab in combination with docetaxel in patients with castrate-resistant metastatic prostate cancer. Patients and methods In this phase 1, open-label, multicenter, nonrandomized study, 75 mg/m\u00b2 docetaxel was administered on Day 1 of each of nine 21-day treatment cycles and intetumumab 5 or 10 mg/kg was administered on Days 1, 8, and 15 of Cycles 2 and 3 and on Day 1 of all subsequent cycles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20145975", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 421, "text": "In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1:1:1:1 to 1000 mg m(-2) dacarbazine+placebo (n=32), 1000 mg m(-2) dacarbazine+10 mg kg(-1) intetumumab (n=32), 10 mg kg(-1) intetumumab (n=33), or 5 mg kg(-1) intetumumab (n=32) q3w.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750555", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 526, "text": "Patients with histologically-confirmed inoperable melanoma or angiosarcoma refractory to standard treatment were allocated to treatment with 10 mg/kg or 20 mg/kg intetumumab, administered once every 3 weeks for up to four cycles unless unacceptable toxicity or disease progression occurred.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331745", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 490, "text": "Data from the Melanoma Subscale (MS) of the Functional Assessment of Cancer Therapy-Melanoma and the worst pain question from the Brief Pain Inventory (BPI) were taken from a clinical trial evaluating intetumumab alone or with dacarbazine in Stage IV metastatic melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027908", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 489, "text": "Data from the Melanoma Subscale (MS) of the Functional Assessment of Cancer Therapy-Melanoma and the worst pain question from the Brief Pain Inventory (BPI) were taken from a clinical trial evaluating intetumumab alone or with dacarbazine in Stage IV metastatic melanoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027908", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 490, "text": "Data from the Melanoma Subscale (MS) of the Functional Assessment of Cancer Therapy-Melanoma and the worst pain question from the Brief Pain Inventory (BPI) were taken from a clinical trial evaluating intetumumab alone or with dacarbazine in Stage IV metastatic melanoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027908", "endSection": "abstract" } ] }, { "body": "Is there any evidence of dysregulated long non coding RNAs and Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23065742", "http://www.ncbi.nlm.nih.gov/pubmed/18587408", "http://www.ncbi.nlm.nih.gov/pubmed/20888417", "http://www.ncbi.nlm.nih.gov/pubmed/22081608", "http://www.ncbi.nlm.nih.gov/pubmed/22996644", "http://www.ncbi.nlm.nih.gov/pubmed/23662159", "http://www.ncbi.nlm.nih.gov/pubmed/23756188" ], "ideal_answer": [ "It is becoming increasingly evident that long non coding RNAs (lncRNAs) play a role on neurodegenerative diseases such as Alzheimer (AD). BACE1-AS, GDNFOS and 17A are examples of these lncRNAs. In some instances those lncRNAs are embedded or transcribed from the opposite strand of coding genes." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022661", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "summary", "id": "533ada5efd9a95ea0d000001", "snippets": [ { "offsetInBeginSection": 865, "offsetInEndSection": 983, "text": "lncRNAs in central nervous system (CNS) development and neurodegenerative diseases, including Alzheimer's disease (AD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23756188", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 115, "text": "(lncRNA) within mRNA sequences of Alzheimer's disease genes, namely, APP, APOE, PSEN1, and PSEN2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23662159", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 120, "text": "sortilin-related receptor 1 (SORL1) is a risk gene for late-onset Alzheimer's disease (AD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22996644", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 368, "text": "non-coding (nc) RNA (hereafter referred to as 51A) that maps in antisense configuration to intron 1 of the SORL1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22996644", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 140, "text": "novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081608", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 563, "text": "GDNFOS gene has four exons that are spliced into different isoforms. GDNFOS1 and GDNFOS2 are long noncoding RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081608", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1081, "text": "In the MTG of AD patients, the mature GDNF peptide was down-regulated; however, the transcript of GDNF isoform from human exon 2 was up-regulated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081608", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1416, "text": "The findings of novel GDNF and GDNFOS isoforms and differences in tissue expression patterns dysregulated in AD brains ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081608", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 320, "text": "novel non-coding (nc) RNA (named 17A) RNA polymerase (pol) III-dependent embedded in the human G-protein-coupled receptor 51 gene (GPR51, GABA B2 receptor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20888417", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 693, "text": "17A is expressed in human brain, and we report that it is upregulated in cerebral tissues derived from Alzheimer disease patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20888417", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 304, "text": "Here we identify a conserved noncoding antisense transcript for beta-secretase-1 (BACE1), a crucial enzyme in Alzheimer's disease pathophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18587408", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1355, "text": "the genotype of this SNP shows different distribution in normal elders, mild cognitive impairment, and Alzheimer disease subjects, suggesting that this lincRNA may have a role in physiology and pathophysiology of human brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23065742", "endSection": "abstract" } ] }, { "body": "Which hormone receptor function is altered in patients with Donohue syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22972224", "http://www.ncbi.nlm.nih.gov/pubmed/24498630", "http://www.ncbi.nlm.nih.gov/pubmed/17201797", "http://www.ncbi.nlm.nih.gov/pubmed/19774849", "http://www.ncbi.nlm.nih.gov/pubmed/23229189", "http://www.ncbi.nlm.nih.gov/pubmed/19882513", "http://www.ncbi.nlm.nih.gov/pubmed/23990696", "http://www.ncbi.nlm.nih.gov/pubmed/18411068", "http://www.ncbi.nlm.nih.gov/pubmed/22768670", "http://www.ncbi.nlm.nih.gov/pubmed/21092701", "http://www.ncbi.nlm.nih.gov/pubmed/23824322" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "MSH: Rare autosomal recessive syndrome of extreme insulin resistance due to mutations in the binding domain of INSULIN RECEPTOR. Clinical features include severe intrauterine and postnatal growth restriction, characteristic dysmorphic FACIES; HIRSUTISM; VIRILIZATION; multiple endocrine abnormalities, and early death.,NCI: A rare autosomal recessive genetic disorder caused by mutations in the insulin receptor gene. Signs and symptoms include a characteristic facial appearance (protuberant and low-set ears, thick lips, and flaring nostrils), intrauterine growth retardation, insulin resistance, and enlarged genitalia." }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17001090", "o": "Leprechaunisms" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A17001090" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17003896", "o": "Syndrome, Donohue" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A18430717" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A17012086" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A13286376", "o": "LEPRECHAUNISM" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A13288574" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A16995573" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18433068", "o": "Leprechaunism" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A18433068" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18430717", "o": "Donohue Syndrome [Disease/Finding]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A13288574", "o": "DONOHUE SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A17003896" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A17689250" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A18444972" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0265344", "o": "http://linkedlifedata.com/resource/umls/label/A13286376" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17012086", "o": "Donohue Syndrome" } ], "ideal_answer": [ "Donohue syndrome (leprechaunism) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. This syndrome is characterized by excessive hyperglycemia with hyperinsulinism, pre- and postnatal growth retardation, distinct dysmorphism and early death. Progressive obstructive cardiomyopathy and renal tubular dysfunction have been described in patients with Donohue syndrome. Milder form of insulin resistance due to insulin receptor gene mutation is coined as Rabson-Mendenhall syndrome." ], "exact_answer": [ "insulin receptor" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050470", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056731", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018000", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051427", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051428", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006728" ], "type": "factoid", "id": "5314bd7ddae131f847000006", "snippets": [ { "offsetInBeginSection": 104, "offsetInEndSection": 247, "text": "This disease is caused by a defective insulin receptor and features abnormal glucose metabolism and retarded intrauterine and postnatal growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23824322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Severe progressive obstructive cardiomyopathy and renal tubular dysfunction in Donohue syndrome with decreased insulin receptor autophosphorylation due to a novel INSR mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229189", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Donohue syndrome (leprechaunism; OMIM *246200) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene (INSR) causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Leprechaunism (Donohue syndrome): a case bearing novel compound heterozygous mutations in the insulin receptor gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22972224", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Leprechaunism (Donohue syndrome) is the most severe type of insulin receptor (INSR) gene anomaly with the majority of patients surviving for only 2 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22972224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A novel mutation of the insulin receptor gene in a preterm infant with Donohue syndrome and heart failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768670", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Donohue syndrome (DS) is a rare autosomal recessive condition caused by mutations in the gene encoding the insulin receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768670", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 578, "text": "Any dysfunction of insulin signalling pathway as a result of insulin receptor gene mutations is linked with various forms of insulin resistance, including insulin resistance type A, Donohue or Rabson-Mendenhall syndrome, which differ in the level of severity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Donohue syndrome in a neonate with homozygous deletion of exon 3 of the insulin receptor gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19774849", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Donohue syndrome describes the clinical consequences of the most severe genetic loss of insulin receptor function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19774849", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "Homozygous or compound heterozygous mutations within the insulin binding domain of the human insulin receptor (INSR) are usually associated with severe impairment of insulin binding leading to Donohue syndrome (\"Leprechaunism\"), which is characterized by excessive hyperglycemia with hyperinsulinism, pre- and postnatal growth retardation, distinct dysmorphism and early death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18411068", "endSection": "abstract" }, { "offsetInBeginSection": 1053, "offsetInEndSection": 1159, "text": "The former mutation has been described in homozygous form in Donohue syndrome, while the latter is novel. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17201797", "endSection": "abstract" } ] }, { "body": "Does triiodothyronine (T3) has cardiac angiogenic effects?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20100314", "http://www.ncbi.nlm.nih.gov/pubmed/2530972", "http://www.ncbi.nlm.nih.gov/pubmed/19074585", "http://www.ncbi.nlm.nih.gov/pubmed/22681587", "http://www.ncbi.nlm.nih.gov/pubmed/19286941" ], "ideal_answer": [ "T3-induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF-BB, PDGFR-\u03b2 and downstream activation of Akt.\nT(3) administration restored TRbeta mRNA expression level in AAC hearts to the control level.\nTRbeta in the coronary ECs regulates capillary density during cardiac development, and down-regulation of TRbeta results in coronary microvascular rarefaction during pathological hypertrophy." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.biosemantics.org/jochem#4005955", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045766", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018919", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002040", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045765", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043924", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043925", "http://www.biosemantics.org/jochem#4275389" ], "type": "yesno", "id": "513f4892bee46bd34c000014", "snippets": [ { "offsetInBeginSection": 1664, "offsetInEndSection": 1802, "text": "T3-induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF-BB, PDGFR-\u03b2 and downstream activation of Akt.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22681587", "endSection": "sections.0" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1073, "text": "L-T3 significantly increased angiogenesis and cell survival and enhanced the expression of nuclear-encoded transcription factors involved in these processes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100314", "endSection": "sections.0" }, { "offsetInBeginSection": 761, "offsetInEndSection": 854, "text": "T(3) administration restored TRbeta mRNA expression level in AAC hearts to the control level.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074585", "endSection": "sections.0" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1049, "text": "Rbeta knockout and TRalpha/TRbeta double-knockout mice both exhibited significantly less capillary density in LV compared with wild-type mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074585", "endSection": "sections.0" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1597, "text": "TRbeta in the coronary ECs regulates capillary density during cardiac development, and down-regulation of TRbeta results in coronary microvascular rarefaction during pathological hypertrophy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074585", "endSection": "sections.0" } ] }, { "body": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "http://www.ncbi.nlm.nih.gov/pubmed/24125847", "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "http://www.ncbi.nlm.nih.gov/pubmed/18617481", "http://www.ncbi.nlm.nih.gov/pubmed/24805197" ], "ideal_answer": [ "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy.The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers.", "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy.The Ser96Ala (S96A) mutation within the histidine rich Ca(2+) binding protein (HRC) has recently been linked to cardiac arrhythmias in idiopathic dilated cardiomyopathy patients, potentially attributable to an increase in spontaneous Ca(2+) release events.", "The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers.The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.", "The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias and sudden death in idiopathic DCM." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:12930" ], "type": "yesno", "id": "54d8f37b4b1fd0d33c000004", "snippets": [ { "offsetInBeginSection": 1207, "offsetInEndSection": 1423, "text": "The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18617481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "The Ser96Ala (S96A) mutation within the histidine rich Ca(2+) binding protein (HRC) has recently been linked to cardiac arrhythmias in idiopathic dilated cardiomyopathy patients, potentially attributable to an increase in spontaneous Ca(2+) release events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24805197", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 211, "text": "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24125847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1403, "text": " HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24125847", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1386, "text": "The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18617481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18617481", "endSection": "title" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1525, "text": "These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "endSection": "abstract" } ] }, { "body": "Are BRAF mutations common in melanoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23415641", "http://www.ncbi.nlm.nih.gov/pubmed/24265154", "http://www.ncbi.nlm.nih.gov/pubmed/24265155", "http://www.ncbi.nlm.nih.gov/pubmed/23890088", "http://www.ncbi.nlm.nih.gov/pubmed/24298448", "http://www.ncbi.nlm.nih.gov/pubmed/23903755", "http://www.ncbi.nlm.nih.gov/pubmed/23900694", "http://www.ncbi.nlm.nih.gov/pubmed/23594689", "http://www.ncbi.nlm.nih.gov/pubmed/23843700", "http://www.ncbi.nlm.nih.gov/pubmed/14679157", "http://www.ncbi.nlm.nih.gov/pubmed/24265153", "http://www.ncbi.nlm.nih.gov/pubmed/23890105", "http://www.ncbi.nlm.nih.gov/pubmed/24220097", "http://www.ncbi.nlm.nih.gov/pubmed/24291778", "http://www.ncbi.nlm.nih.gov/pubmed/24252159", "http://www.ncbi.nlm.nih.gov/pubmed/23237741", "http://www.ncbi.nlm.nih.gov/pubmed/24283590", "http://www.ncbi.nlm.nih.gov/pubmed/24248543", "http://www.ncbi.nlm.nih.gov/pubmed/18375819", "http://www.ncbi.nlm.nih.gov/pubmed/24201813", "http://www.ncbi.nlm.nih.gov/pubmed/16799476", "http://www.ncbi.nlm.nih.gov/pubmed/23893853", "http://www.ncbi.nlm.nih.gov/pubmed/23890154", "http://www.ncbi.nlm.nih.gov/pubmed/24289205", "http://www.ncbi.nlm.nih.gov/pubmed/24309328", "http://www.ncbi.nlm.nih.gov/pubmed/24325952", "http://www.ncbi.nlm.nih.gov/pubmed/22614711", "http://www.ncbi.nlm.nih.gov/pubmed/24073999", "http://www.ncbi.nlm.nih.gov/pubmed/24258972", "http://www.ncbi.nlm.nih.gov/pubmed/24258977", "http://www.ncbi.nlm.nih.gov/pubmed/24258979", "http://www.ncbi.nlm.nih.gov/pubmed/15917418", "http://www.ncbi.nlm.nih.gov/pubmed/23477830", "http://www.ncbi.nlm.nih.gov/pubmed/24259661", "http://www.ncbi.nlm.nih.gov/pubmed/24295639", "http://www.ncbi.nlm.nih.gov/pubmed/24202393", "http://www.ncbi.nlm.nih.gov/pubmed/14695152", "http://www.ncbi.nlm.nih.gov/pubmed/23414474", "http://www.ncbi.nlm.nih.gov/pubmed/23273605" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7124", "o": "UMLS_CUI:C1511021" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7124", "o": "BRAF Gene Mutation" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7124", "o": "NCI2009_04D:C40430" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7636217", "o": "C40430" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1511021", "o": "http://linkedlifedata.com/resource/umls/label/A7636217" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7636217", "o": "BRAF Gene Mutation" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1511021", "o": "http://linkedlifedata.com/resource/umls/label/A7636217" } ], "ideal_answer": [ "Melanoma is the most aggressive form of skin cancer. The treatment of patients with advanced melanoma is rapidly evolving due to an improved understanding of molecular drivers of this disease. Somatic mutations in BRAF are the most common genetic alteration found in these tumors. BRAF mutations occur in approximately 8% of all human cancers and approach 50% in melanoma and papillary carcinoma of thyroid.", "Activating mutations in the BRAF gene occur in approximately 50% of melanomas. More than 70% of BRAF mutations are V600E and 10-30% are V600K. BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048493", "http://www.uniprot.org/uniprot/BRAF_CHICK", "http://www.uniprot.org/uniprot/BRAF_COTJA", "http://www.disease-ontology.org/api/metadata/DOID:1909" ], "type": "yesno", "id": "5512c91b6a8cde6b7200000b", "snippets": [ { "offsetInBeginSection": 125, "offsetInEndSection": 160, "text": "patients with BRAF-mutant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23903755", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 607, "text": "BRAF-mutated melanoma ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23900694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "The RAS/RAF/MEK/ERK pathway has been reported to be activated in over 80% of all cutaneous melanomas, making it the focus of many scientific studies in the melanoma field. Discoveries of mutations and aberrant expression of components in this cascade, in particular, BRAF and NRAS render a deeper understanding of the mechanisms responsible for oncogenesis and provide new therapeutic strategies for this deadly disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23893853", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1010, "text": " BRAF-targeted therapies (e.g., vemurafenib, dabrafenib) have showed impressive results in systemic therapy for melanoma harboring activating BRAF V600E mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23893853", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 460, "text": " An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890154", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 746, "text": " a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun-exposed melanomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890154", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 100, "text": "Treatment of advanced melanoma has been improved with the advent of the BRAF inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "BRAF is the most prevalent oncogene and an important therapeutic target in melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23890088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "Activating BRAF mutations, leading to constitutive activation of the MAPK signaling pathway, are common in a variety of human cancers. Several small molecule BRAF inhibitors have been developed during the last years and shown promising results in clinical trials, especially for metastatic melanoma, while they have been less effective in colon cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309328", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 849, "text": "BRAF V600 selective inhibitors have been approved for the treatment of V600 mutation positive metastatic melanoma, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298448", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 67, "text": "BRAF(V600) mutation-positive melanoma ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295639", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Melanoma is the most aggressive form of skin cancer. The treatment of patients with advanced melanoma is rapidly evolving due to an improved understanding of molecular drivers of this disease. Somatic mutations in BRAF are the most common genetic alteration found in these tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291778", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 146, "text": " genetically activated BRAF, is now commonly prescribed for metastatic melanoma harboring a BRAF mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24289205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "BRAF inhibitors improve melanoma patient survival, but resistance invariably develops. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24283590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BRAF inhibitors elicit rapid antitumor responses in the majority of patients with BRAF(V600)-mutant melanoma, but acquired drug resistance is almost universal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265153", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 900, "text": "BRAF(V600E) mutation confers constitutive BRAK kinase activation in melanoma cells, promoting tumor growth. This discovery led to the development of BRAF kinase inhibitors like vemurafenib and dabrafenib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "(V600)BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24258979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The Braf(V600E) mutation has been detected in patients with metastatic melanoma, colon, thyroid, and other cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24258977", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 365, "text": "Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorporate prognostic and predictive biomarkers into treatment decisions for their melanoma patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24258972", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "BRAF mutations occur in approximately 8% of all human cancers and approach 50% in melanoma and papillary carcinoma of thyroid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Vemurafenib is a selective and potent small molecule inhibitor of the V600 mutant form of the BRAF protein used in the treatment of melanoma and colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24248543", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1290, "text": "Molecular studies demonstrated that the melanoma was positive for the 1799T>A (V600E) mutation in the BRAF gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24220097", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "RAF kinase inhibitors have substantial therapeutic effects in patients with BRAF-mutant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24202393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "An activating BRAF (V600E) kinase mutation occurs in approximately half of melanomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24201813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Activating mutations in the BRAF gene occur in approximately 50% of melanomas. More than 70% of BRAF mutations are V600E and 10-30% are V600K.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23237741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Activating BRAF mutations, leading to constitutive activation of the MAPK signaling pathway, are common in a variety of human cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325952", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 353, "text": "Several small molecule BRAF inhibitors have been developed during the last years and shown promising results in clinical trials, especially for metastatic melanoma, while they have been less effective in colon cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "Personalized melanoma medicine has progressed from histopathologic features to serum markers to molecular profiles. Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorporate prognostic and predictive biomarkers into treatment decisions for their melanoma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24258972", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 160, "text": "The clinical activity of BRAF inhibitor (BRAF-I) therapy is a major breakthrough in the treatment of metastatic melanoma carrying BRAF mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24073999", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 479, "text": "The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843700", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 384, "text": "BRAF represents one of the most frequently mutated protein kinase genes in human tumours. The mutation is commonly tested in pathology practice. BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594689", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1035, "text": "Indeed, recent clinical trials involving BRAF selective inhibitors exhibited promising response rates in metastatic melanoma patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594689", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 865, "text": "A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk (MAPK) signal transduction pathway. The discovery of activating BRAF mutations in \u223c50% of all melanomas has proved to be a turning point in the therapeutic management of the disseminated disease. This review summarizes the critical role of BRAF in melanoma pathophysiology, the clinical and pathological determinants of BRAF mutation status and finally addresses the current state of the art of BRAF inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23415641", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 1328, "text": "To better understand the BRAF mutation profile in melanomas, we retrospectively analyzed data from 1112 primary and metastatic melanomas at our institution. The cohort included nonacral cutaneous (n = 774), acral (n = 111), mucosal (n = 26), uveal (n = 23), leptomeningeal (n = 1), and metastatic melanomas of unknown primary site (n = 177). BRAF mutation hotspot regions in exons 11 and 15 were analyzed by pyrosequencing or with the primer extension MassARRAY system. A total of 499 (44.9%) specimens exhibited BRAF mutations, involving exon 15 [497 (99.6%)] or exon 11 [2 (0.4%)]. p.V600E was detected in 376 (75.4%) cases; the remaining 123 (24.6%) cases exhibited non-p.V600E mutations, of which p.V600K was most frequent [86 (17.2%)]. BRAF mutations were more frequent in nonacral cutaneous (51.4%) than acral melanomas [18 (16.2%)] (P < 0.001); however, there was no significant difference among cutaneous histological subtypes. All mucosal, uveal, and leptomeningeal melanomas were BRAF wild type (WT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23273605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Recently, it was reported that BRAF mutations are frequent in melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14695152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Activating mutations in BRAF are the most common genetic alterations in melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23477830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Oncogenic BRAF and NRAS mutations are frequent in malignant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18375819", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 608, "text": "Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15917418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "BRAF mutations are common events in a variety of melanocytic nevi and primary cutaneous melanomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16799476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Approximately 40-60% of melanomas from Caucasian populations carry activating mutations in the BRAF oncogene, with the most common being the p.Val600Glu (V600E) hotspot mutation in exon 15", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22614711", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 497, "text": "Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14679157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BRAF mutations have been identified as the most common oncogene mutation in melanomas, especially important in those originating on nonchronically sun-damaged skin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23414474", "endSection": "abstract" } ] }, { "body": "Is it possible to determine the proteome of a formalin fixed and paraffin embedded (FFPE) tissue?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21117664", "http://www.ncbi.nlm.nih.gov/pubmed/20373499", "http://www.ncbi.nlm.nih.gov/pubmed/16091476", "http://www.ncbi.nlm.nih.gov/pubmed/20604508", "http://www.ncbi.nlm.nih.gov/pubmed/20373500", "http://www.ncbi.nlm.nih.gov/pubmed/22387116", "http://www.ncbi.nlm.nih.gov/pubmed/22081483", "http://www.ncbi.nlm.nih.gov/pubmed/19522851", "http://www.ncbi.nlm.nih.gov/pubmed/17409379", "http://www.ncbi.nlm.nih.gov/pubmed/21370020", "http://www.ncbi.nlm.nih.gov/pubmed/19637237", "http://www.ncbi.nlm.nih.gov/pubmed/19467989", "http://www.ncbi.nlm.nih.gov/pubmed/19128014", "http://www.ncbi.nlm.nih.gov/pubmed/20469934", "http://www.ncbi.nlm.nih.gov/pubmed/21337705", "http://www.ncbi.nlm.nih.gov/pubmed/22352854", "http://www.ncbi.nlm.nih.gov/pubmed/19471015", "http://www.ncbi.nlm.nih.gov/pubmed/20597554", "http://www.ncbi.nlm.nih.gov/pubmed/22015969", "http://www.ncbi.nlm.nih.gov/pubmed/22188123", "http://www.ncbi.nlm.nih.gov/pubmed/22318899" ], "ideal_answer": [ "Yes, advances in sample preparation has enabled the proteomic analysis of formalin-fixed and paraffin-embedded tissues." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016610", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "yesno", "id": "511a1e12df1ebcce7d000009", "snippets": [ { "offsetInBeginSection": 212, "offsetInEndSection": 426, "text": "ver the last few years, advances in methodology have made it possible to recover peptides from FFPE tissues that yield a reasonable representation of the proteins recovered from identical fresh or frozen specimens.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21370020", "endSection": "sections.0" }, { "offsetInBeginSection": 1552, "offsetInEndSection": 1665, "text": "Thus, laser capture microdissection of FFPE tissue coupled with downstream proteomic analysis is a valid approach", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081483", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22387116", "endSection": "sections.0" }, { "offsetInBeginSection": 202, "offsetInEndSection": 472, "text": "Recent improvements in proteomics technologies, from the 2D gel analysis of intact proteins to the \"shotgun\" quantification of peptides and the use of isobaric tags for absolute and relative quantification (iTRAQ) method, have made the analysis of FFPE tissues possible.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22188123", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The ability to investigate the proteome of formalin-fixed, paraffin-embedded (FFPE) tissues can be considered a major recent achievement in the field of clinical proteomics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21337705", "endSection": "sections.0" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1362, "text": "The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22387116", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Proteomic analysis of formalin-fixed paraffin-embedded pancreatic tissue using liquid chromatography tandem mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22015969", "endSection": "title" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1522, "text": "We report that differentially expressed proteins can be identified among FFPE tissue specimens originating from individuals with different pancreatic histologic findings.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22015969", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Formalin-fixed paraffin-embedded (FFPE) proteome analysis using gel-free and gel-based proteomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20604508", "endSection": "title" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1313, "text": "This study will facilitate the development of future proteomic analysis of FFPE tissue and provide a tool for the validation in archival samples of biomarkers of exposure, prognosis and disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20604508", "endSection": "sections.0" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1426, "text": "The CAAR method presented here complements previously described antigen-retrieval protocols and is an important step in being able to fully analyze the proteome of archived FFPE tissue.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20597554", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Proteome, phosphoproteome, and N-glycoproteome are quantitatively preserved in formalin-fixed paraffin-embedded tissue and analyzable by high-resolution mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20469934", "endSection": "title" }, { "offsetInBeginSection": 132, "offsetInEndSection": 339, "text": "It has only recently been shown that proteins in FFPE tissues can be identified by mass spectrometry-based proteomics but analysis of post-translational modifications is thought to be difficult or impossible", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20469934", "endSection": "sections.0" }, { "offsetInBeginSection": 694, "offsetInEndSection": 846, "text": "Results from the FFPE-FASP procedure do not indicate any discernible changes due to storage time, hematoxylin staining or laser capture microdissection.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20469934", "endSection": "sections.0" }, { "offsetInBeginSection": 1310, "offsetInEndSection": 1443, "text": "Thus, FFPE biobank material can be analyzed by quantitative proteomics at the level of proteins and post-translational modifications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20469934", "endSection": "sections.0" }, { "offsetInBeginSection": 429, "offsetInEndSection": 722, "text": "A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16091476", "endSection": "sections.0" }, { "offsetInBeginSection": 1467, "offsetInEndSection": 1627, "text": "espite using tissue blocks stored for as many as 28 years, high confidence and comparative proteome analysis between the leiomyomas and the sarcoma is achieved.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19128014", "endSection": "sections.0" }, { "offsetInBeginSection": 1725, "offsetInEndSection": 1943, "text": "These findings demonstrate that formalin fixation, paraffin processing, and LCM do not negatively impact protein quality and quantity as determined by MS and that FFPE samples are amenable to global proteomic analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19471015", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Protein extraction of formalin-fixed, paraffin-embedded tissue enables robust proteomic profiles by mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19471015", "endSection": "title" } ] }, { "body": "What is known about type D personality trait in cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22850265", "http://www.ncbi.nlm.nih.gov/pubmed/19819126", "http://www.ncbi.nlm.nih.gov/pubmed/21531672", "http://www.ncbi.nlm.nih.gov/pubmed/24368251", "http://www.ncbi.nlm.nih.gov/pubmed/22459997", "http://www.ncbi.nlm.nih.gov/pubmed/21943928", "http://www.ncbi.nlm.nih.gov/pubmed/23423829" ], "ideal_answer": [ "Reported prevalence rates of type D personality ranges from 19% to 22% in patients with cancer. In patients with cancer, Type D personality is associated with poor quality of life and mental health. Cancer patients with a Type D personality as compared with non-Type D patients perceive that they receive less information, report less satisfaction with the amount of received information, believe that their illness has significantly more serious consequences, will last significantly longer, and experience significantly more symptoms that they attribute to their illness. Also, they are more concerned about their illness, and their disease more often influences them emotionally. Also, Type D cancer patients are at an increased risk for comorbidity burden and increased health care utilization." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064415" ], "type": "summary", "id": "54f48cb74e9bf3263f000001", "snippets": [ { "offsetInBeginSection": 760, "offsetInEndSection": 1815, "text": "RESULTS: Nineteen percent of patients (n=572) had a Type D personality. The perceived receipt of disease-specific (mean 46 vs. 51), medical test (56 vs. 63) and treatment information (37 vs. 42) was significantly lower for Type D patients compared with non-Type Ds as assessed with the EORTC QLQ-INFO25 (scales 0-100; all ps<0.01). Cancer patients with a Type D personality were less satisfied with the received information (49 vs. 58; p<0.01) and found the received information less useful (55 vs. 61; p<0.01) compared with non-Type Ds. Multivariate linear regression analyses showed that Type D personality was independently associated with information about the disease (Beta=-0.09), medical tests (Beta=-0.12) and treatment (Beta=-0.08), and with satisfaction with information received (OR=0.54; 95%CI=0.44-0.66;all ps<0.01). CONCLUSIONS: This study showed that patients with a Type D personality perceived that they received less information and reported less satisfaction with the amount of received information as compared with non-Type D patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23423829", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 890, "text": "RESULTS: 750 (19%) patients had a Type D personality. They believe their illness has significantly more serious consequences, will last significantly longer, and experience significantly more symptoms that they attribute to their illness. Also, they are more concerned about their illness, and their disease more often influences them emotionally. Differences regarding 'consequences', 'concern' and 'emotional response' were also clinically relevant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850265", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1901, "text": "Significant differences in perceptions on cause of disease between Type Ds and non-Type Ds were found for psychological distress (16.2 vs. 10.9%; p<0.01), randomness (1.7 vs. 5.3%; p<0.01) and unknown (18.8 vs. 24.4%; p<0.01). Multivariate analyses showed that Type D was negatively associated with 'coherence' and positively with 'consequences', 'timeline', 'identity', 'concern', and 'emotional representation'. CONCLUSIONS: These results elucidate the associations between personality and illness perceptions, demonstrating their close interrelatedness. Our study may be helpful in further developing theoretical models regarding giving meaning to illness and the illness perceptions that the illness elicits. Future studies should investigate whether interventions can positively impact illness perceptions of Type D cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850265", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 1605, "text": "RESULTS: Nineteen percent of survivors had a type D personality. Over a 12-month period, type D survivors significantly more often reported osteoarthritis, back pain, and depression than non-type D survivors. Also, type D survivors more often reported to feel bothered by high blood pressure, osteoarthritis, heart disease, depression, diabetes and lung disease during daily activities. Type D survivors more often visited their general practitioner than non-type D survivors (P<.001), also in relation to cancer (0 visits: 54% vs. 60%; 1-5: 28% vs. 22%; >5: 9% vs. 5%; P<.001), as well as their specialist (0 visits: 6% vs. 7%; 1-5 visits: 59% vs. 64%; >5 visits: 30% vs. 23%; P<.01). CONCLUSION: Type D personality is a vulnerability factor that may help to identify subgroups of cancer survivors who are at an increased risk for comorbidity burden and increased health care utilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22459997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Type D (distressed) personality is associated with poor quality of life and mental health among 3080 cancer survivors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21943928", "endSection": "title" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1678, "text": "CONCLUSIONS: Cancer survivors with a Type D personality are at increased risk of impaired QoL and mental health problems that cannot be explained by socio-demographic or clinical characteristics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21943928", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1063, "text": "FINDINGS: Patients with type D personality experienced higher physical and psychological distress than those with non-type D personality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21531672", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 1477, "text": "RESULTS: Twenty-two percent of survivors (n=125) were classified as Type D. They reported a clinically and statistically significant worse general health (57.8 versus 75.6), social functioning (73.1 versus 88.7), mental health (61.7 versus 80.6), more emotional role limitations (67.8 versus 89.4) and less vitality (54.5 versus 72.8) than non-Type D patients. Additionally, they reported a statistically and clinically relevant higher impact of cancer on body changes, negative self-evaluation, negative outlook on life, life interferences and health worry. Furthermore, they were more worried about the influence of the sun on their skin and acted accordingly. No differences were found in health care utilisation. CONCLUSIONS: Type D personality has a distinct negative impact on health status in melanoma survivors and is an important factor to screen for in clinical practice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19819126", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1163, "text": "Cancer patients with a Type D personality were less satisfied with the received information (49 vs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23423829", "endSection": "abstract" } ] }, { "body": "List available tools for genomic visualisation in comparative genomics", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25249626", "http://www.ncbi.nlm.nih.gov/pubmed/15123592", "http://www.ncbi.nlm.nih.gov/pubmed/23193262" ], "ideal_answer": [ "Insyght, Genomicus and Sockeye." ], "exact_answer": [ [ "Insyght" ], [ "Genomicus" ], [ "Sockeye" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281" ], "type": "list", "id": "56acc7ca0a360a5e45000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Insyght: navigating amongst abundant homologues, syntenies and gene functional annotations in bacteria, it's that symbol!", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25249626", "endSection": "title" }, { "offsetInBeginSection": 517, "offsetInEndSection": 835, "text": "Insyght is a comparative genomic visualization tool that combines three complementary displays: (i) a table for thoroughly browsing amongst homologues, (ii) a comparator of orthologue functional annotations and (iii) a genomic organization view designed to improve the legibility of rearrangements and distinctive loci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25249626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Genomicus: five genome browsers for comparative genomics in eukaryota", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in>150 eukaryote genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Sockeye: a 3D environment for comparative genomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15123592", "endSection": "title" }, { "offsetInBeginSection": 428, "offsetInEndSection": 628, "text": "We have developed a Java-based application called Sockeye that uses three-dimensional (3D) graphics technology to facilitate the visualization of annotation and conservation across multiple sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15123592", "endSection": "abstract" } ] }, { "body": "Which species may be used for the biotechnological production of itaconic acid?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23298766", "http://www.ncbi.nlm.nih.gov/pubmed/1366363", "http://www.ncbi.nlm.nih.gov/pubmed/22480369", "http://www.ncbi.nlm.nih.gov/pubmed/22956279", "http://www.ncbi.nlm.nih.gov/pubmed/22752264", "http://www.ncbi.nlm.nih.gov/pubmed/17697977", "http://www.ncbi.nlm.nih.gov/pubmed/17451943", "http://www.ncbi.nlm.nih.gov/pubmed/23397482", "http://www.ncbi.nlm.nih.gov/pubmed/22925689", "http://www.ncbi.nlm.nih.gov/pubmed/21324422", "http://www.ncbi.nlm.nih.gov/pubmed/20461508", "http://www.ncbi.nlm.nih.gov/pubmed/23420787", "http://www.ncbi.nlm.nih.gov/pubmed/12146646" ], "ideal_answer": [ "In 1955, the production of itaconic acid was firstly described for Ustilago maydis. Some Aspergillus species, like A. itaconicus and A. terreus, show the ability to synthesize this organic acid and A. terreus can secrete significant amounts to the media. Itaconic acid is mainly supplied by biotechnological processes with the fungus Aspergillus terreus. Cloning of the cadA gene into the citric acid producing fungus A. niger showed that it is possible to produce itaconic acid also in a different host organism." ], "exact_answer": [ [ "Aspergillus terreus" ], [ "Aspergillus niger" ], [ "Ustilago maydis" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001426", "http://www.biosemantics.org/jochem#4276340", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0047370", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005656", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0047613" ], "type": "list", "id": "515ffc2b298dcd4e51000035", "snippets": [ { "offsetInBeginSection": 4, "offsetInEndSection": 77, "text": "continuous itaconic acid production from sucrose with Aspergillus terreus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1366363", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "A potent itaconic acid producing strain, Aspergillus terreus SKR10, was isolated from horticulture waste", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12146646", "endSection": "sections.0" }, { "offsetInBeginSection": 526, "offsetInEndSection": 614, "text": "Two high itaconic acid yielding mutants, N45 and UNCS1 were obtained by gradient plating", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12146646", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Itaconic acid production using sago starch hydrolysate by Aspergillus terreus TN484-M1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17451943", "endSection": "title" }, { "offsetInBeginSection": 34, "offsetInEndSection": 110, "text": "production of itaconic acid and lovastatin by Aspergillus terreus ATCC 20542", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17697977", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Fermentation products of Aspergillus terreus ATCC 20542 (a parent strain for lovastatin production) were collected, and the coexistence of itaconic acid (IA) with lovastatin was confirmed in this study", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17697977", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Enhancing itaconic acid production by Aspergillus terreus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20461508", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Aspergillus terreus is successfully used for industrial production of itaconic acid", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20461508", "endSection": "sections.0" }, { "offsetInBeginSection": 250, "offsetInEndSection": 444, "text": "From a number of different Aspergillus terreus controlled batch fermentations, those cultures with the largest difference in itaconic acid titer and productivity were selected for mRNA isolation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21324422", "endSection": "sections.0" }, { "offsetInBeginSection": 237, "offsetInEndSection": 335, "text": "a systematic process optimization was performed with an own isolated strain of Aspergillus terreus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22752264", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Cells of Aspergillus terreus, free and immobilized in polyurethane foam, were employed in itaconic acid fermentation processes on glycerol-based media.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22956279", "endSection": "sections.0" }, { "offsetInBeginSection": 206, "offsetInEndSection": 306, "text": "current biotechnological production processes with the fungus Aspergillus terreus has to be improved", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23298766", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Reduced by-product formation and modified oxygen availability improve itaconic acid production in Aspergillus niger", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23397482", "endSection": "title" }, { "offsetInBeginSection": 141, "offsetInEndSection": 303, "text": "Previously, it was shown that expression of the cis-aconitate decarboxylase gene (cadA) from Aspergillus terreus converted A. niger into an itaconic acid producer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23397482", "endSection": "sections.0" } ] }, { "body": "Which types of cancer can be recognized and treated by the use of immunotherapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24324949", "http://www.ncbi.nlm.nih.gov/pubmed/24286020", "http://www.ncbi.nlm.nih.gov/pubmed/24325394", "http://www.ncbi.nlm.nih.gov/pubmed/23133825", "http://www.ncbi.nlm.nih.gov/pubmed/15199397", "http://www.ncbi.nlm.nih.gov/pubmed/24297569", "http://www.ncbi.nlm.nih.gov/pubmed/24294369", "http://www.ncbi.nlm.nih.gov/pubmed/20146807", "http://www.ncbi.nlm.nih.gov/pubmed/15212694", "http://www.ncbi.nlm.nih.gov/pubmed/24324117", "http://www.ncbi.nlm.nih.gov/pubmed/24319203", "http://www.ncbi.nlm.nih.gov/pubmed/24295643", "http://www.ncbi.nlm.nih.gov/pubmed/24213679", "http://www.ncbi.nlm.nih.gov/pubmed/24062490", "http://www.ncbi.nlm.nih.gov/pubmed/24290058", "http://www.ncbi.nlm.nih.gov/pubmed/24292706", "http://www.ncbi.nlm.nih.gov/pubmed/23780988", "http://www.ncbi.nlm.nih.gov/pubmed/24327937", "http://www.ncbi.nlm.nih.gov/pubmed/2139701", "http://www.ncbi.nlm.nih.gov/pubmed/24327934", "http://www.ncbi.nlm.nih.gov/pubmed/24327938" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1883488", "o": "2002-0936" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1883488", "o": "neoplasm/cancer immunotherapy" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0935453", "o": "http://linkedlifedata.com/resource/umls/label/A1883488" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C0935453", "o": "http://linkedlifedata.com/resource/umls/id/C0597030" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1883501", "o": "neoplasm/cancer therapy" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A1883488", "o": "CRISP Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0597030", "o": "http://linkedlifedata.com/resource/umls/id/C0935453" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18170672", "o": "LP78314-9" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18170672", "o": "Date 1st immunotherapy treatment | Cancer XXX" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2601766", "o": "http://linkedlifedata.com/resource/umls/label/A18170672" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7636954", "o": "C15974" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7636954", "o": "Biological Cancer Immunotherapy" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1511142", "o": "http://linkedlifedata.com/resource/umls/label/A7636961" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1511142", "o": "http://linkedlifedata.com/resource/umls/label/A7636954" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7636961", "o": "Biological Immunotherapy for Cancer" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7650034", "o": "Immunotherapy, Cancer, Biological" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1511142", "o": "http://linkedlifedata.com/resource/umls/label/A7650034" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7636961", "o": "C15974" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7650034", "o": "C15974" } ], "ideal_answer": [ "When normal cells turn into cancer cells, some of the antigens on their surface change. These cells, like many body cells, constantly shed bits of protein from their surface into the circulatory system. Often, tumor antigens are among the shed proteins.\nThese shed antigens prompt action from immune defenders, including cytotoxic T cells, natural killer cells, and macrophages. According to one theory, patrolling cells of the immune system provide continuous bodywide surveillance, catching and eliminating cells that undergo malignant transformation. Tumors develop when this immune surveillance breaks down or is overwhelmed.\nA new approach to cancer therapy uses antibodies that have been specially made to recognize specific cancers such as Melanoma, Leukaemia, Lung Cancer, Colorectal Cancer, Breast Cancer, Head Cancer and Pancreatic Cancer." ], "exact_answer": [ [ "Melanoma" ], [ "Leukaemia" ], [ "Lung Cancer" ], [ "Colorectal Cancer" ], [ "Breast Cancer" ], [ "Head Cancer" ], [ "Pancreatic Cancer" ], [ "Prostate tumor" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006258", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019496", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007167", "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016219", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016233" ], "type": "list", "id": "5321badd9b2d7acc7e00000a", "snippets": [ { "offsetInBeginSection": 265, "offsetInEndSection": 1521, "text": "omising expansion of antigen-specific T cells, the clinical responses following vaccination have been limited, indicating that further improvements of DC vaccine potency are necessary. Pre-clinical studies suggest that vaccination with combination of primary DC subsets, such as myeloid and plasmacytoid blood DCs (mDCs and pDCs, respectively), may result in stronger clinical responses. However, it is a challenge to obtain high enough numbers of primary DCs for immunotherapy, since their frequency in blood is very low. We therefore explored the possibility to generate them from hematopoietic progenitor cells (HPCs). Here, we show that by inhibiting the aryl hydrocarbon receptor with its antagonist StemRegenin 1 (SR1), clinical-scale numbers of functional BDCA2(+)BDCA4(+) pDCs, BDCA1(+) mDCs, and BDCA3(+)DNGR1(+) mDCs can be efficiently generated from human CD34(+) HPCs. The ex vivo-generated DCs were phenotypically and functionally comparable to peripheral blood DCs. They secreted high levels of pro-inflammatory cytokines such as interferon (IFN)-\u03b1, interleukin (IL)-12, and tumor necrosis factor (TNF)-\u03b1 and upregulated co-stimulatory molecules and maturation markers following stimulation with Toll-like receptor (TLR) ligands. Further, the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325394", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 1017, "text": "odent models of prostate cancer have served as valuable preclinical models to evaluate novel treatments and understand malignant disease progression. In particular, a transgenic rat autochthonous model of prostate cancer using the SV40 large T antigen expressed under a prostate-specific probasin promoter was previously developed as a model of androgen-dependent prostate cancer (TRAP). In the current report, we backcrossed this strain to the Lewis strain, an inbred rat strain better characterized for immunological analyses. We demonstrate that Lewis transgenic rats (Lew-TRAP) developed prostate adenocarcinomas with 100% penetrance by 25 weeks of age. Tumors were predominantly androgen-dependent, as castration prevented tumor growth in the majority of animals. Finally, we demonstrate that Lew-TRAP rats could be immunized with a DNA vaccine encoding a human prostate tumor antigen (prostatic acid phosphatase) with the development of Lewis strain-specific T-cell responses. We propose", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24324949", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 870, "text": " we analyzed NY-ESO-1 expression in 222 melanoma specimens, including 16 primary and 206 metastatic tumors. Our results support previous findings showing higher expression of NY-ESO-1 in metastatic (58/206; 28.2%) versus primary (0/16) tumors. In addition, our results show that the epithelioid subtype of melanoma has the highest incidence of NY-ESO-1 expression. These findin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24290058", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 374, "text": " Immunotherapy is a highly promising form of cancer treatment, but its efficacy can be severely compromised by an immunosuppressive tumor microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24327938", "endSection": "abstract" } ] }, { "body": "What is the typical rash associated with gluten ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6742871", "http://www.ncbi.nlm.nih.gov/pubmed/21159258", "http://www.ncbi.nlm.nih.gov/pubmed/15489956", "http://www.ncbi.nlm.nih.gov/pubmed/8881298", "http://www.ncbi.nlm.nih.gov/pubmed/11247893", "http://www.ncbi.nlm.nih.gov/pubmed/15033190", "http://www.ncbi.nlm.nih.gov/pubmed/2438879", "http://www.ncbi.nlm.nih.gov/pubmed/9407155", "http://www.ncbi.nlm.nih.gov/pubmed/4026376", "http://www.ncbi.nlm.nih.gov/pubmed/14632800", "http://www.ncbi.nlm.nih.gov/pubmed/7549032", "http://www.ncbi.nlm.nih.gov/pubmed/15981987", "http://www.ncbi.nlm.nih.gov/pubmed/12459520", "http://www.ncbi.nlm.nih.gov/pubmed/8521118", "http://www.ncbi.nlm.nih.gov/pubmed/9824575", "http://www.ncbi.nlm.nih.gov/pubmed/7947207", "http://www.ncbi.nlm.nih.gov/pubmed/22547981", "http://www.ncbi.nlm.nih.gov/pubmed/15953332", "http://www.ncbi.nlm.nih.gov/pubmed/17340026", "http://www.ncbi.nlm.nih.gov/pubmed/12485471", "http://www.ncbi.nlm.nih.gov/pubmed/3804022", "http://www.ncbi.nlm.nih.gov/pubmed/680606", "http://www.ncbi.nlm.nih.gov/pubmed/9814827" ], "ideal_answer": [ "Dermatitis herpetiformis is a lifelong, gluten-sensitive, blistering skin disease with pathognomonic immunoglobulin (Ig)A deposits in the papillary dermis." ], "exact_answer": [ "dermatitis herpetiformis" ], "type": "factoid", "id": "55180ef46487737b43000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Dermatitis herpetiformis (DH) is an autoimmunity-driven inflammatory blistering dermatosis associated with a gluten-dependent enteropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22547981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Dermatitis herpetiformis is an autoimmune blistering disease that appears as a cutaneous manifestation of gluten intolerance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159258", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 845, "text": "Treatment of dermatitis herpetiformis is based on a life-long, strict gluten-free diet, which improves all clinical aspects of gluten sensitivity, and dapsone, a drug that is only effective for the skin manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Dermatitis herpetiformis and coeliac disease are gluten-sensitive diseases that share immunopathological mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17340026", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 491, "text": "We report the unusual case of an 8-month-old child presenting to his general practitioner with pruritic skin lesions, subsequently proven to be dermatitis herpetiformis (DH) as the first sign of gluten-sensitive disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15953332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15489956", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 927, "text": " These findings may relate to the fact, that dermatitis herpetiformis is associated with gluten sensitive enteropathy, coeliac disease, which is characterised by IgA type autoantibodies to a closely related enzyme, tissue transglutaminase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15033190", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1440, "text": " There is growing evidence that dermatitis herpetiformis should be considered as the skin manifestation of gluten sensitivity developing in those patients with mild coeliac disease, who produce epidermal transglutaminase autoantibodies of high avidity and affinity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15033190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: A life-long gluten-free diet is the treatment of choice for dermatitis herpetiformis, which is considered to be coeliac disease of the skin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14632800", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1582, "text": "We report long-term clinical and histological remissions in seven patients with dermatitis herpetiformis after the reintroduction of dietary gluten.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14632800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Gluten sensitive enteropathy has various manifestations, of which the two major forms are classical coeliac disease (cCD) and dermatitis herpetiformis (DH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12485471", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 331, "text": "The major significant advances in our understanding of DH have been the demonstration that DH patients also have coeliac diseases (CD) and that the rash is also gluten dependent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12459520", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 755, "text": "Despite the fact that it has been known for over fifty years that gluten causes the enteropathy of CD, and for over thirty years the rash of DH, it is still not known how gluten produces these effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12459520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "BACKGROUND: Dermatitis herpetiformis (DH) is a specific dermatological manifestation of coeliac disease and 80% of DH patients have gluten sensitive enteropathy manifested by crypt hyperplasia and villous atrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11247893", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 490, "text": "The presence of a rash is also a sensitive indicator of gluten ingestion in dermatitis herpetiformis, and this was used to study whether patients with this disease could also tolerate oats. PATIENTS/METHODS: Eleven patients with dermatitis herpetiformis in remission on a gluten-free diet were challenged daily with 50 g oats for six months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9824575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Dermatitis herpetiformis (DH) is a lifelong, gluten-sensitive, blistering skin disease with pathognomonic immunoglobulin (Ig)A deposits in the papillary dermis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9814827", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1629, "text": "CONCLUSIONS: Patients with dermatitis herpetiformis can include moderate amounts of oats in their gluten-free diets without deleterious effects to the skin or intestine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9407155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND: Dermatitis herpetiformis (DH) is a chronic papulovesicular immune-mediated disorder associated with gluten-sensitive enteropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8881298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Serum IgA class antigliadin antibodies (IgA-AGA) are increased in untreated patients with coeliac disease and dermatitis herpetiformis (DH), and it has been suggested that salivary IgA-AGA measurements could be used as a non-invasive screening test for gluten-sensitive enteropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8521118", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 751, "text": "Despite the fact that it has been known for over fifty years that gluten causes the enteropathy of CD, and for over thirty years the rash of DH, it is still not known how gluten produces these effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12459520", "endSection": "abstract" }, { "offsetInBeginSection": 1318, "offsetInEndSection": 1565, "text": "The central role of gluten in childhood dermatitis herpetiformis is evidenced by the fact that a gluten free diet helps the damaged jejunal mucosa to recover and controls the rash even in those children who do not have an abnormal jejunal biopsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6742871", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 329, "text": "The major significant advances in our understanding of DH have been the demonstration that DH patients also have coeliac diseases (CD) and that the rash is also gluten dependent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12459520", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1415, "text": "The results confirm the absence of oat toxicity on the gluten sensitive small bowel mucosa and suggest that the rash in patients with dermatitis herpetiformis is not activated by eating oats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9824575", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 325, "text": "The presence of a rash is also a sensitive indicator of gluten ingestion in dermatitis herpetiformis, and this was used to study whether patients with this disease could also tolerate oats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9824575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15489956", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 784, "text": "This contrasts to the situation in dermatitis herpetiformis, where both the rash and the enteropathy are gluten dependent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2438879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15489956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Dermatitis herpetiformis (DH) is a chronic papulovesicular immune-mediated disorder associated with gluten-sensitive enteropathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8881298", "endSection": "abstract" } ] }, { "body": "Which proteins constitute the methyl-directed mismatch repair system (MMR) in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21940221", "http://www.ncbi.nlm.nih.gov/pubmed/14602928", "http://www.ncbi.nlm.nih.gov/pubmed/12067333", "http://www.ncbi.nlm.nih.gov/pubmed/16414311", "http://www.ncbi.nlm.nih.gov/pubmed/9852252", "http://www.ncbi.nlm.nih.gov/pubmed/11591694", "http://www.ncbi.nlm.nih.gov/pubmed/8244947", "http://www.ncbi.nlm.nih.gov/pubmed/1920448", "http://www.ncbi.nlm.nih.gov/pubmed/15709980", "http://www.ncbi.nlm.nih.gov/pubmed/10652107", "http://www.ncbi.nlm.nih.gov/pubmed/18687413", "http://www.ncbi.nlm.nih.gov/pubmed/15503140", "http://www.ncbi.nlm.nih.gov/pubmed/12860461", "http://www.ncbi.nlm.nih.gov/pubmed/19192394", "http://www.ncbi.nlm.nih.gov/pubmed/22473602", "http://www.ncbi.nlm.nih.gov/pubmed/20018207", "http://www.ncbi.nlm.nih.gov/pubmed/24214875", "http://www.ncbi.nlm.nih.gov/pubmed/12513688", "http://www.ncbi.nlm.nih.gov/pubmed/19474347", "http://www.ncbi.nlm.nih.gov/pubmed/24062730", "http://www.ncbi.nlm.nih.gov/pubmed/17951114", "http://www.ncbi.nlm.nih.gov/pubmed/20971907", "http://www.ncbi.nlm.nih.gov/pubmed/20921378", "http://www.ncbi.nlm.nih.gov/pubmed/11952911", "http://www.ncbi.nlm.nih.gov/pubmed/3280983", "http://www.ncbi.nlm.nih.gov/pubmed/23228104", "http://www.ncbi.nlm.nih.gov/pubmed/19029144", "http://www.ncbi.nlm.nih.gov/pubmed/15113836" ], "ideal_answer": [ "The mismatch repair system (MMR) recognizes and corrects mismatched or unpaired bases caused mainly by DNA polymerase, and contributes to the fidelity of DNA replication in living cells. In bacteria, the methyldirected mismatch repair (MMR) is comprised of MutS and MutL proteins, encoded by the mutS/L operon." ], "exact_answer": [ [ "mutS" ], [ "mutL" ], [ "mutH" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006298" ], "type": "list", "id": "5540eda30083d1bf0e000006", "snippets": [ { "offsetInBeginSection": 427, "offsetInEndSection": 472, "text": "MutY and MutSL (mismatch repair system [MMR])", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20971907", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 60, "text": "Escherichia coli DNA Mismatch Repair (MMR) protein MutS ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 424, "text": "We have characterized the mismatch repair system (MMR) of the highly radiation-resistant type strain of Deinococcus radiodurans, ATCC 13939. We show that the MMR system is functional in this organism, where it participates in ensuring the fidelity of DNA replication and recombination. The system relies on the activity of two key proteins, MutS1 and MutL, which constitute a conserved core involved in mismatch recognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15503140", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 479, "text": "the mutS/L operon essential for methyldirected mismatch repair (MMR) activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11952911", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "The mismatch repair system (MMR) recognizes and corrects mismatched or unpaired bases caused mainly by DNA polymerase, and contributes to the fidelity of DNA replication in living cells. In Escherichia coli, the MutHLS system is known to function in MMR, and homologues of MutS and MutL are widely conserved in almost all organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15113836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "A simple genetic system has been developed to test the effect of over-expression of wild-type or mutated human MutL homologue 1 (hMLH1) proteins on methyl-directed mismatch repair (MMR) in Escherichia coli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12513688", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 753, "text": "Among these six mutated genes was mutS, which encodes a component of the methyl-directed mismatch repair (MMR) system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473602", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 529, "text": "The majority of naturally occurring, strong mutators contain defects in the methyl-directed mismatch repair (MMR) system, with mutations in mutS predominating.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12860461", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 385, "text": "The picture of MutH-independent MMR in other bacteria is less clear, as MMR components other than MutS and MutL have not been identified in the majority of bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21940221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "The methyl-directed mismatch repair (MMR) mechanism has been extensively studied in vitro and in vivo, but one of the difficulties in determining the biological relationships between the MMR-related proteins is the tendency of MutL to self-aggregate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19192394", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 757, "text": "Among these six mutated genes was mutS, which encodes a component of the methyl-directed mismatch repair (MMR) system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "MutL is required to assist the mismatch repair protein MutS during initiation of the methyl-directed mismatch repair (MMR) response in various organisms ranging from prokaryotes to eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19029144", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 495, "text": "Moreover, methyl-directed mismatch repair (MMR) is known to trigger sensitivity to methylating agents via a mechanism that involves recognition by MutS of the O(6)-mG:T replication intermediates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921378", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 424, "text": "The system relies on the activity of two key proteins, MutS1 and MutL, which constitute a conserved core involved in mismatch recognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15503140", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 314, "text": "In Escherichia coli, the best studied mismatch repair (MMR) pathway is the methyl-directed long patch repair system which is mediated by three gene products; MutS, MutL and MutH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9852252", "endSection": "abstract" }, { "offsetInBeginSection": 1118, "offsetInEndSection": 1367, "text": "Cells devoid of MutS1 or MutL proteins were as resistant to gamma-rays, mitomycin C and UV-irradiation as wild-type bacteria, suggesting that the mismatch repair system is not essential for the reconstitution of a functional genome after DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15503140", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 423, "text": "The system relies on the activity of two key proteins, MutS1 and MutL, which constitute a conserved core involved in mismatch recognition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15503140", "endSection": "abstract" } ] }, { "body": "Is aganglionic megacolon a feature of Down syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23045564", "http://www.ncbi.nlm.nih.gov/pubmed/18075983", "http://www.ncbi.nlm.nih.gov/pubmed/2309705", "http://www.ncbi.nlm.nih.gov/pubmed/12028658" ], "ideal_answer": [ "Down syndrome (DS) is recognized by characteristic facial features, intellectual disability, and an increased risk for cardiac malformations and duodenal atresia. Recently, Hirschsprung disease (HSCR), or congenital aganglionic megacolon, has been seen more often among patients with DS." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14250" ], "type": "yesno", "id": "550311dae9bde69634000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Down syndrome (DS) is recognized by characteristic facial features, intellectual disability, and an increased risk for cardiac malformations and duodenal atresia. Recently, Hirschsprung disease (HSCR), or congenital aganglionic megacolon, has been seen more often among patients with DS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23045564", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1078, "text": "Of the 17 patients with HD who were studied, 10 were isolated (58.8%) and seven (41.1%) were associated to other structural abnormalities and psychomotor retardation. Three of the cases in this latter group were due to chromosome pathology (trisomy 21, Down syndrome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18075983", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 408, "text": "The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12028658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 760, "text": "Hirschsprung disease, or congenital aganglionic megacolon, is commonly assumed to be a sex-modified multifactorial trait. To test this hypothesis, complex segregation analysis was performed on data on 487 probands and their families. Demographic information on probands and the recurrence risk to relatives of probands are presented. An increased sex ratio (3.9 male:female) and an elevated risk to sibs (4%), as compared with the population incidence (0.02%), are observed, with the sex ratio decreasing and the recurrence risk to sibs increasing as the aganglionosis becomes more extensive. Down syndrome was found at an increased frequency among affected individuals but not among their unaffected sibs, and the increase was not associated with maternal age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2309705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12028658", "endSection": "title" }, { "offsetInBeginSection": 100, "offsetInEndSection": 293, "text": " The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12028658", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 294, "text": "The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12028658", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 293, "text": "The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12028658", "endSection": "abstract" } ] }, { "body": "Which is the vector of Louping ill virus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21593276", "http://www.ncbi.nlm.nih.gov/pubmed/14422369", "http://www.ncbi.nlm.nih.gov/pubmed/9802086", "http://www.ncbi.nlm.nih.gov/pubmed/21254926", "http://www.ncbi.nlm.nih.gov/pubmed/12557579", "http://www.ncbi.nlm.nih.gov/pubmed/19631009", "http://www.ncbi.nlm.nih.gov/pubmed/19925041", "http://www.ncbi.nlm.nih.gov/pubmed/12233771", "http://www.ncbi.nlm.nih.gov/pubmed/15252984", "http://www.ncbi.nlm.nih.gov/pubmed/18562534", "http://www.ncbi.nlm.nih.gov/pubmed/7815482", "http://www.ncbi.nlm.nih.gov/pubmed/17346361", "http://www.ncbi.nlm.nih.gov/pubmed/12560576", "http://www.ncbi.nlm.nih.gov/pubmed/18823640", "http://www.ncbi.nlm.nih.gov/pubmed/19685082", "http://www.ncbi.nlm.nih.gov/pubmed/18602711", "http://www.ncbi.nlm.nih.gov/pubmed/18841330", "http://www.ncbi.nlm.nih.gov/pubmed/22452970", "http://www.ncbi.nlm.nih.gov/pubmed/11427261", "http://www.ncbi.nlm.nih.gov/pubmed/18471057", "http://www.ncbi.nlm.nih.gov/pubmed/22913287", "http://www.ncbi.nlm.nih.gov/pubmed/13383364", "http://www.ncbi.nlm.nih.gov/pubmed/12519399", "http://www.ncbi.nlm.nih.gov/pubmed/22939093", "http://www.ncbi.nlm.nih.gov/pubmed/1337231", "http://www.ncbi.nlm.nih.gov/pubmed/21771532" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/pubmed/keyword/VIRUSES%2Flouping-ill", "o": "http://linkedlifedata.com/resource/pubmed/Keyword" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A2035145", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2035145", "o": "D004669" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A2035145", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2035145", "o": "Louping ill viruses" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/keyword/VIRUSES%2Flouping-ill", "o": "VIRUSES/louping-ill" }, { "p": 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"http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0431097", "o": "11086" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0431097", "o": "NCBI Taxonomy" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0431097", "o": "Louping ill virus" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0081054", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0081054", "o": "Metathesaurus Names" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0081054", "o": "Louping Ill" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0423465", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0423465", "o": "D008146" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0423465", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0423465", "o": "Ill, Louping" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A8352613", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8352613", "o": "063.1" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8352613", "o": "ICD-9-CM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8352613", "o": "Louping ill" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:10250", "o": "http://www.w3.org/2004/02/skos/core#Concept" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:10250", "o": "Louping ill" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:10250", "o": "Louping ill (disorder)" } ], "ideal_answer": [ "Louping ill virus (LIV) belongs to the mammalian tick-borne virus group of the genus Flavivirus which cause central nervous system disease. LIV infects the red grouse Lagopus lagopus scoticus, causing high mortality. LIV is transmitted by the tick Ixodes ricinus.", "Deer are the key hosts of the vector (Ixodes ricinus) that transmits LIV to red grouse Lagopus lagopus scoticus, causing high mortality. (PMID: 22939093)" ], "exact_answer": [ "Ixodes ricinus" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014780", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001179", "http://www.disease-ontology.org/api/metadata/DOID:10250", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004669", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004199", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004675", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008146" ], "type": "factoid", "id": "51716e808ed59a060a00000b", "snippets": [ { "offsetInBeginSection": 528, "offsetInEndSection": 664, "text": "Deer are the key hosts of the vector (Ixodes ricinus) that transmits LIV to red grouse Lagopus lagopus scoticus, causing high mortality.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22939093", "endSection": "sections.0" }, { "offsetInBeginSection": 94, "offsetInEndSection": 426, "text": "n Europe the primary arthropod vectors of zoonotic diseases are ticks, which transmit Borrelia burgdorferi sensu lato (the agent of Lyme disease), tick-borne encephalitis virus and louping ill virus between humans, livestock and wildlife. Ixodes ricinus ticks and reported tick-borne disease cases are currently increasing in the UK", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19685082", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Many vector-borne pathogens whose primary vectors are generalists, such as Ixodid ticks, can infect a wide range of host species and are often zoonotic.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19631009", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Tick-borne encephalitis virus (TBEV) and Louping ill virus (LIV) are viruses in the Mammalian tick-borne virus group/genus Flavivirus, causing central nervous system disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18471057", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The complex pathogen-host-vector system of the tick-borne louping-ill virus causes economic losses to sheep and red grouse in upland United Kingdom.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346361", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 396, "text": "For pathogens transmitted by biting vectors, one of the fundamental assumptions is often that vector bites are the sole or main route of host infection. Here, we demonstrate experimentally a transmission route whereby hosts (red grouse, Lagopus lagopus scoticus) became infected with a member of the tick-borne encephalitis virus complex, louping ill virus, after eating the infected tick vector.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15252984", "endSection": "sections.0" }, { "offsetInBeginSection": 411, "offsetInEndSection": 527, "text": "We used Susceptible Infected Recovered (SIR) models parameterized for the tick-borne louping ill virus (LIV) system.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22939093", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "This study has examined the efficacy following intramuscular administration of a recombinant Semliki Forest virus (rSFV) vaccine, encoding the prME and NS1 proteins of louping ill virus (LIV), in sheep.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11427261", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Since the recognition that louping-ill, known for well over 100 years as an epizootic disease of sheep in Scotland, was caused by a virus transmitted by arthropods, many other arthropod-borne viruses capable of causing encephalitis in domestic animals or man have been discovered.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14422369", "endSection": "sections.0" } ] }, { "body": "Does HuR protein regulate the splicing process?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18463097", "http://www.ncbi.nlm.nih.gov/pubmed/21890634", "http://www.ncbi.nlm.nih.gov/pubmed/19931428", "http://www.ncbi.nlm.nih.gov/pubmed/24865968", "http://www.ncbi.nlm.nih.gov/pubmed/20951677", "http://www.ncbi.nlm.nih.gov/pubmed/24566137", "http://www.ncbi.nlm.nih.gov/pubmed/23312841", "http://www.ncbi.nlm.nih.gov/pubmed/24066065", "http://www.ncbi.nlm.nih.gov/pubmed/24210824", "http://www.ncbi.nlm.nih.gov/pubmed/25422430", "http://www.ncbi.nlm.nih.gov/pubmed/23052832" ], "ideal_answer": [ "HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA", "Recent research demonstrated that SIRT1 pre-mRNA undergoes alternative splicing to produce different isoforms, such as SIRT1 full-length and SIRT1-\u2206Exon8 variants. Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances: HuR increased SIRT1-\u2206Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-\u2206Exon8 mRNA levels. This study provides novel insight into how the alternative splicing of SIRT1 pre-mRNA is regulated, which has fundamental implications for understanding the critical and multifunctional roles of SIRT1. Further, endothelial-specific Elavl1 knockout mice exhibited reduced revascularization after hind limb ischemia and tumor angiogenesis in oncogene-induced mammary cancer, resulting in attenuated blood flow and tumor growth, respectively.", "Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition. HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances. Overexpression and knockdown of HuR led to Fas exon 6 skipping and inclusion, respectively. These results suggest that the TIA and HuR cellular ratio influences cell-type specific Fas exon 6 splicing pattern." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0000398", "http://amigo.geneontology.org/amigo/term/GO:0008380", "http://amigo.geneontology.org/amigo/term/GO:0036002", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000067780" ], "type": "yesno", "id": "56c5a7605795f9a73e000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24566137", "endSection": "title" }, { "offsetInBeginSection": 762, "offsetInEndSection": 970, "text": "Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24566137", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1137, "text": "HuR increased SIRT1-\u2206Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-\u2206Exon8 mRNA levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24566137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "HuR regulates alternative splicing of the TRA2\u03b2 gene in human colon cancer cells under oxidative stress", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865968", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Hu antigen R (HuR) regulates stress responses through stabilizing and/or facilitating the translation of target mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865968", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 553, "text": "We show here that the RBP embryonic lethal abnormal vision like 1 (ELAVL1, also know as HuR) regulates the alternative splicing of eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1), which encodes an eukaryotic translation initiation factor 4E transporter (4E-T) protein and suppresses the expression of capped mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25422430", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1085, "text": "Further, endothelial-specific Elavl1 knockout mice exhibited reduced revascularization after hind limb ischemia and tumor angiogenesis in oncogene-induced mammary cancer, resulting in attenuated blood flow and tumor growth, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25422430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24210824", "endSection": "title" }, { "offsetInBeginSection": 577, "offsetInEndSection": 810, "text": "Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3' UTR of transcripts of this cytoplasmic RNA virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24210824", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 533, "text": "Here we demonstrate that expression of 2A(pro) induces a selective nucleo-cytoplasm translocation of several important RNA binding proteins and splicing factors. Subcellular fractionation studies, together with immunofluorescence microscopy revealed an asymmetric distribution of HuR and TIA1/TIAR in 2A(pro) expressing cells, which modulates splicing of the human Fas exon 6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24066065", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 670, "text": "knockdown of HuR or overexpression of TIA1/TIAR, leads to Fas exon 6 inclusion in 2A(pro)-expressing cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24066065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The differential expression levels of T-cell intracellular antigens (TIA) and Hu antigen R (HuR) are concomitant with a splicing switch in apoptosis receptor Fas in HCT-116 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20951677", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 394, "text": "overexpression and knockdown of HuR led to Fas exon 6 skipping and inclusion, respectively. These results suggest that the TIA and HuR cellular ratio influences cell-type specific Fas exon 6 splicing pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20951677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463097", "endSection": "title" }, { "offsetInBeginSection": 182, "offsetInEndSection": 387, "text": "antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463097", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1000, "text": "ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23052832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463097", "endSection": "title" }, { "offsetInBeginSection": 168, "offsetInEndSection": 389, "text": "I report that antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463097", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24210824", "endSection": "title" }, { "offsetInBeginSection": 846, "offsetInEndSection": 951, "text": "Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463097", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24566137", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "HuR regulates alternative splicing of the TRA2\u03b2 gene in human colon cancer cells under oxidative stress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865968", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The HuR protein regulates the expression of thousands of cellular transcripts by modulating mRNA splicing, trafficking, translation, and stability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23052832", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1122, "text": "Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. Taken together, these results support a functional link between HuR as repressor of alternative Fas splicing and the molecular mechanisms modulating programmed cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463097", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 764, "text": "We are interested in interactions involving hnRNP proteins participating in several steps of mRNA processing (mainly pre-mRNA splicing) and HuR with an established role in stability/translation of associated mRNAs. hnRNP and HuR proteins have a major nucleoplasmic localization and ability to shuttle between nucleus and cytoplasm. We report here on interactions between hnRNP and HuR proteins that were identified in the context of isolated hnRNP and mRNP complexes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19931428", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 855, "text": "Despite the fact that HuR sites are observed in intronic regions, our data do not support a role for HuR in regulating splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21890634", "endSection": "abstract" } ] }, { "body": "Is Titin the largest single protein molecule found in Nature?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16453158", "http://www.ncbi.nlm.nih.gov/pubmed/2129545", "http://www.ncbi.nlm.nih.gov/pubmed/16702235", "http://www.ncbi.nlm.nih.gov/pubmed/1859393", "http://www.ncbi.nlm.nih.gov/pubmed/12187564", "http://www.ncbi.nlm.nih.gov/pubmed/14600266", "http://www.ncbi.nlm.nih.gov/pubmed/19134271", "http://www.ncbi.nlm.nih.gov/pubmed/21257761", "http://www.ncbi.nlm.nih.gov/pubmed/21075826", "http://www.ncbi.nlm.nih.gov/pubmed/14572168", "http://www.ncbi.nlm.nih.gov/pubmed/19962382", "http://www.ncbi.nlm.nih.gov/pubmed/1582406" ], "ideal_answer": [ "Titin, is definitely the largest protein in the body, with a molecular weight of 3 million Dalton and composed of 27,000 amino acids. Titin is the largest protein known to date and acts as a mechanosensor that regulates muscle protein expression in a sarcomere strain-dependent fashion.", "Yes. Titin, the largest protein in the human body, is well known as a molecular spring in muscle cells and scaffold protein aiding myofibrillar assembly. Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions.", "Titin is the largest protein known to date and acts as a mechanosensor that regulates muscle protein expression in a sarcomere strain-dependent fashion.Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere.", "Titin is the largest protein known, and is essential for organising muscle sarcomeres.The giant sarcomere protein titin/connectin is the largest protein known to date." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/TITIN_DROME", "http://www.uniprot.org/uniprot/TITIN_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019368" ], "type": "yesno", "id": "55030a6ce9bde6963400000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Titin, the largest protein in the human body, is well known as a molecular spring in muscle cells and scaffold protein aiding myofibrillar assembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21257761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Titin is the largest protein in mammals; it forms an elastic filament along the myofibril of cardiac and skeletal muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19962382", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 178, "text": "Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19134271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16702235", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 738, "text": "The giant sarcomere protein titin/connectin is the largest protein known to date.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16453158", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1077, "text": "Titin is the largest protein known to date and acts as a mechanosensor that regulates muscle protein expression in a sarcomere strain-dependent fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21075826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Titin is the largest protein known, and is essential for organising muscle sarcomeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14600266", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 205, "text": "It has many domains with a variety of functions, and stretches from the Z-line to the M-line in the muscle sarcomere. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14600266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Titin, is definitely the largest protein in the body, with a molecular weight of 3 million Dalton and composed of 27,000 amino acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12187564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1859393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2129545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Titin is at present the largest known protein (M(r) 3000 kDa) and its expression is restricted to vertebrate striated muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1582406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Titin is the largest protein known, and is essential for organising muscle sarcomeres", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14600266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Titin is at present the largest known protein (M(r) 3000 kDa) and its expression is restricted to vertebrate striated muscle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1582406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2129545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19134271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Titin, the biggest single (poly) peptide found in humans, and throughout nature so far, was long considered as a good candidate for inherited muscle diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14572168", "endSection": "abstract" } ] }, { "body": "what is the role of MEF-2 in cardiomyocyte differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19498465", "http://www.ncbi.nlm.nih.gov/pubmed/17158926", "http://www.ncbi.nlm.nih.gov/pubmed/8366095", "http://www.ncbi.nlm.nih.gov/pubmed/22850285", "http://www.ncbi.nlm.nih.gov/pubmed/23261540", "http://www.ncbi.nlm.nih.gov/pubmed/12663654", "http://www.ncbi.nlm.nih.gov/pubmed/22199256", "http://www.ncbi.nlm.nih.gov/pubmed/24091702", "http://www.ncbi.nlm.nih.gov/pubmed/10790371", "http://www.ncbi.nlm.nih.gov/pubmed/9857019" ], "triples": [ { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/A2ICN5", "o": "http://purl.uniprot.org/go/0030154" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0030154", "o": "http://www.geneontology.org/go#GO:0030154" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/A2ICN5", "o": "http://linkedlifedata.com/resource/#_413249434E3500C" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0030154", "o": "cell differentiation" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413249434E3500C", "o": "Myocyte-specific enhancer factor 2A" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/A2VDZ3", "o": "http://purl.uniprot.org/go/0030154" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/A2VDZ3", "o": "http://linkedlifedata.com/resource/#_413256445A3300B" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413256445A3300B", "o": "Myocyte-specific enhancer factor 2A" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q5REW7", "o": "http://purl.uniprot.org/go/0030154" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q5REW7", "o": "http://linkedlifedata.com/resource/#_51355245573700A" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51355245573700A", "o": "Myocyte-specific enhancer factor 2A" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q9W6U8", "o": "http://purl.uniprot.org/go/0030154" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q9W6U8", "o": "http://linkedlifedata.com/resource/#_513957365538009" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513957365538009", "o": "Myocyte-specific enhancer factor 2A" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q8CFN5", "o": "http://purl.uniprot.org/go/0003211" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0003211", "o": "http://www.geneontology.org/go#GO:0003211" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q8CFN5", "o": "http://linkedlifedata.com/resource/#_513843464E35001D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513843464E35001D", "o": "Myocyte-specific enhancer factor 2C" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0003211", "o": "cardiac ventricle formation" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/A2ICN5", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0030154" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0030154", "o": "cell differentiation" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/A2VDZ3", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0030154" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q5REW7", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0030154" }, { "p": "http://linkedlifedata.com/resource/relationontology/participateInBiologicalProcess", "s": "http://purl.uniprot.org/uniprot/Q9W6U8", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0030154" } ], "ideal_answer": [ "The myocyte enhancer factor-2 (MEF2) proteins are MADS-box transcription factors that are essential for differentiation of all muscle lineages but their mechanisms of action remain largely undefined. MEF2C expression initiates cardiomyogenesis, resulting in the up-regulation of Brachyury T, bone morphogenetic protein-4, Nkx2-5, GATA-4, cardiac alpha-actin, and myosin heavy chain expression. Inactivation of the MEF2C gene causes cardiac developmental arrest and severe downregulation of a number of cardiac markers including atrial natriuretic factor (ANF). BMP-2, a regulator of cardiac development during embryogenesis, was shown to increase PI 3-kinase activity in cardiac precursor cells, resulting in increased expression of sarcomeric myosin heavy chain (MHC) and MEF-2A. Furthermore, expression of MEF-2A increased MHC expression in a PI 3-kinase-dependent manner. Other studies showed that Gli2 and MEF2C proteins form a complex, capable of synergizing on cardiomyogenesis-related promoters. Dominant interference of calcineurin/mAKAP binding blunts the increase in MEF2 transcriptional activity seen during myoblast differentiation, as well as the expression of endogenous MEF2-target genes. These findings show that MEF-2 can direct early stages of cell differentiation into a cardiomyogenic pathway." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032383", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035051", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064326" ], "type": "summary", "id": "532f043ed6d3ac6a34000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "The growth and differentiation factor bone morphogenetic protein-2 (BMP-2) regulates cardiac development during vertebrate embryogenesis. In cardiac precursor cells, BMP-2 has recently been shown to induce expression of cardiac transcription factors, including myocyte enhancer factor 2A (MEF-2A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12663654", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 689, "text": "BMP-2 increased PI 3-kinase activity in these cells in a time-dependent manner, resulting in increased expression of sarcomeric myosin heavy chain (MHC) and MEF-2A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12663654", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1637, "text": "Furthermore expression of MEF-2A increased MHC expression in a PI 3-kinase-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12663654", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 773, "text": "Gene expression profiling revealed decreased levels of transcription factors transforming growth factor-\u03b2/bone morphogenetic protein, serum response factor, GATA4, and myocyte enhancer factor 2, linked to increased Ca(2+)-dependent calcineurin activity and Notch1 signaling that impaired ESC differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24091702", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1221, "text": "Dominant interference of calcineurin/mAKAP binding blunts the increase in MEF2 transcriptional activity seen during myoblast differentiation, as well as the expression of endogenous MEF2-target genes. Furthermore, disruption of calcineurin binding to mAKAP in cardiac myocytes inhibits adrenergic-induced cellular hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261540", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 1088, "text": "Hypertrophic agonist stimulation of neonatal ventricular cardiomyocytes increased Mef2 expression by enhancing its translation, without changing its transcription or blocking degradation of the protein. MEF2 abundance was increased by Calcineurin overexpression in vivo and was reduced by Calcineurin inhibition in vitro, without affecting Mef2 mRNA levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850285", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 1321, "text": "In addition, chromatin immunoprecipitation (ChIP) revealed association of Gli2 to the Mef2c gene, and of MEF2C to the Gli2 gene in differentiating P19 cells. Finally, co-immunoprecipitation studies showed that Gli2 and MEF2C proteins formed a complex, capable of synergizing on cardiomyogenesis-related promoters containing both Gli- and MEF2-binding elements. We propose a model whereby Gli2 and MEF2C bind each other's regulatory elements, activate each other's expression and form a protein complex that synergistically activates transcription, enhancing cardiac muscle development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22199256", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 635, "text": "MC1568 arrests myogenesis by (i) decreasing myocyte enhancer factor 2D (MEF2D) expression, (ii) by stabilizing the HDAC4-HDAC3-MEF2D complex, and (iii) paradoxically, by inhibiting differentiation-induced MEF2D acetylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19498465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "The myocyte enhancer factor 2 (MEF2) family of transcription factors is not only important for controlling gene expression in normal cellular programs, like muscle differentiation, T-cell apoptosis, neuronal survival, and synaptic differentiation, but has also been linked to cardiac hypertrophy and other pathological conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158926", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1534, "text": "Furthermore, the nuclear receptor corepressor SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) stimulated the deacetylase activity of HDAC3 towards MEF2 and PCAF. Supporting the physical interaction and deacetylase activity, HDAC3 repressed MEF2-dependent transcription and inhibited myogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The myocyte enhancer factor-2 (MEF2) proteins are MADS-box transcription factors that are essential for differentiation of all muscle lineages but their mechanisms of action remain largely undefined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790371", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 497, "text": "Inactivation of the MEF2C gene causes cardiac developmental arrest and severe downregulation of a number of cardiac markers including atrial natriuretic factor (ANF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790371", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 967, "text": "We provide evidence that MEF2 proteins are recruited to target promoters by the cell-specific GATA transcription factors, and that MEF2 potentiates the transcriptional activity of this family of tissue-restricted zinc finger proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790371", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 737, "text": "During differentiation into cardiac muscle, Nkx2-5 expression resulted in the activation of myocyte enhancer factor 2C (MEF2C), but not MEF2A, -B, or -D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9857019", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1113, "text": "Similar to Nkx2-5, MEF2C expression initiated cardiomyogenesis, resulting in the up-regulation of Brachyury T, bone morphogenetic protein-4, Nkx2-5, GATA-4, cardiac alpha-actin, and myosin heavy chain expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9857019", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1314, "text": "These findings indicate the presence of a positive regulatory network between Nkx2-5 and MEF2C and show that both factors can direct early stages of cell differentiation into a cardiomyogenic pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9857019", "endSection": "abstract" } ] }, { "body": "Which are the main components of mTORC1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21413931", "http://www.ncbi.nlm.nih.gov/pubmed/17461779", "http://www.ncbi.nlm.nih.gov/pubmed/24331524", "http://www.ncbi.nlm.nih.gov/pubmed/18614546", "http://www.ncbi.nlm.nih.gov/pubmed/20127721", "http://www.ncbi.nlm.nih.gov/pubmed/17141160", "http://www.ncbi.nlm.nih.gov/pubmed/17878222" ], "ideal_answer": [ "The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth and is a key target for therapeutic intervention in cancer. Two complexes of mTOR have been identified: complex 1 (mTORC1), consisting of mTOR, Raptor (regulatory associated protein of mTOR) and mLST8 (mammalian lethal with SEC13 protein 8) and complex 2 (mTORC2) consisting of mTOR, Rictor (rapamycin-insensitive companion of mTOR), Sin1 (stress-activated protein kinase-interacting protein 1), and mLST8." ], "exact_answer": [ [ "mTOR" ], [ "Raptor" ], [ "mLST8/GbetaL" ] ], "type": "list", "id": "56cdf3745795f9a73e000039", "snippets": [ { "offsetInBeginSection": 1248, "offsetInEndSection": 1461, "text": "Raptor-mTOR and Rictor-mTOR complexes compete for association with LST8, and this mechanism may contribute to the reciprocal negative regulations of mTORC1 and mTORC2 activities, in terms of their LST8 components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24331524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17141160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth. Two complexes of mTOR have been identified: complex 1, consisting of mTOR-Raptor (regulatory associated protein of mTOR)-mLST8 (termed mTORC1), and complex 2, comprising mTOR-Rictor (rapamycininsensitive companion of mTOR)-mLST8-Sin1 (termed mTORC2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17461779", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1279, "text": "composition of mTORC1 (raptor, mTOR, and GbetaL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17878222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The mammalian target of rapamycin (mTOR) is part of two distinct complexes, mTORC1, containing raptor and mLST8, and mTORC2, containing rictor, mLST8 and sin1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18614546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The mTORC1 protein kinase complex consists of mTOR, raptor, mLST8/GbetaL and PRAS40.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20127721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 524, "text": "The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth and is a key target for therapeutic intervention in cancer. Two complexes of mTOR have been identified: complex 1 (mTORC1), consisting of mTOR, Raptor (regulatory associated protein of mTOR) and mLST8 (mammalian lethal with SEC13 protein 8) and complex 2 (mTORC2) consisting of mTOR, Rictor (rapamycin-insensitive companion of mTOR), Sin1 (stress-activated protein kinase-interacting protein 1), mLST8 and Protor-1 or Protor-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21413931", "endSection": "abstract" } ] }, { "body": "What is the the Menzerath-Altmann law?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22197514" ], "ideal_answer": [ "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics. The random breakage and variants keeping genome size and chromosome number independent raise no serious objection to the relevance of correlations consistent with Menzerath-Altmann law across taxonomic groups and the possibility of a connection between human language and genomes through that law. ", "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics", "Menzerath-Altmann law is a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics.", "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics " ], "type": "summary", "id": "5545d847bf90a13052000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197514", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1222, "text": "The random breakage and variants keeping genome size and chromosome number independent raise no serious objection to the relevance of correlations consistent with Menzerath-Altmann law across taxonomic groups and the possibility of a connection between human language and genomes through that law", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197514", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1218, "text": "The random breakage and variants keeping genome size and chromosome number independent raise no serious objection to the relevance of correlations consistent with Menzerath-Altmann law across taxonomic groups and the possibility of a connection between human language and genomes through that law.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197514", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1223, "text": "The random breakage and variants keeping genome size and chromosome number independent raise no serious objection to the relevance of correlations consistent with Menzerath-Altmann law across taxonomic groups and the possibility of a connection between human language and genomes through that law.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197514", "endSection": "abstract" } ] }, { "body": "Which receptor(s) recognize lysosomal hydrolases in trans-Golgi network (TGN)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18088323", "http://www.ncbi.nlm.nih.gov/pubmed/15078903", "http://www.ncbi.nlm.nih.gov/pubmed/9668075", "http://www.ncbi.nlm.nih.gov/pubmed/17596511", "http://www.ncbi.nlm.nih.gov/pubmed/22264539", "http://www.ncbi.nlm.nih.gov/pubmed/16787435", "http://www.ncbi.nlm.nih.gov/pubmed/11408573", "http://www.ncbi.nlm.nih.gov/pubmed/19224451", "http://www.ncbi.nlm.nih.gov/pubmed/23322049", "http://www.ncbi.nlm.nih.gov/pubmed/22266136", "http://www.ncbi.nlm.nih.gov/pubmed/8577031", "http://www.ncbi.nlm.nih.gov/pubmed/17606993", "http://www.ncbi.nlm.nih.gov/pubmed/8603911", "http://www.ncbi.nlm.nih.gov/pubmed/22884962", "http://www.ncbi.nlm.nih.gov/pubmed/11387475", "http://www.ncbi.nlm.nih.gov/pubmed/18195106", "http://www.ncbi.nlm.nih.gov/pubmed/9247639", "http://www.ncbi.nlm.nih.gov/pubmed/11470415", "http://www.ncbi.nlm.nih.gov/pubmed/22907655", "http://www.ncbi.nlm.nih.gov/pubmed/3000696", "http://www.ncbi.nlm.nih.gov/pubmed/18431031", "http://www.ncbi.nlm.nih.gov/pubmed/7642698", "http://www.ncbi.nlm.nih.gov/pubmed/15976452", "http://www.ncbi.nlm.nih.gov/pubmed/7642697", "http://www.ncbi.nlm.nih.gov/pubmed/18992238", "http://www.ncbi.nlm.nih.gov/pubmed/8718666" ], "ideal_answer": [ "The majority of lysosomal hydrolases in trans-Golgi network (TGN) are specifically recognized by mannose 6-phosphate (M6P) receptors (MPRs), which ensure their transport to the endosomal/lysosomal system. Other receptors can also carry lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system. These M6P alternative receptors are the lysosomal integral membrane protein (LIMP-2) and the multi-ligand receptor sortilin. These reseptors enable a mannose-6-phosphate-independent pathway from TGN to lysosomes." ], "exact_answer": [ [ "mannose 6-phosphate receptors (MPRs)" ], [ "sortilin" ], [ "lysosomal integral membrane protein (LIMP-2)" ], [ "cation-independent mannose 6-phosphate receptor (CI-MPR)" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005802", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090160" ], "type": "list", "id": "554101d0234c5a7c75000002", "snippets": [ { "offsetInBeginSection": 435, "offsetInEndSection": 655, "text": "The majority of the enzymes leave the TGN after modification with mannose-6-phosphate (M6P) residues, which are specifically recognized by M6P receptors (MPRs), ensuring their transport to the endosomal/lysosomal system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884962", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 785, "text": "M6P receptors play a major role in the intracellular transport of newly synthesized lysosomal enzymes in mammalian cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Mannose 6-phosphate receptors (MPRs) are known to be shuttled between the trans-Golgi network (TGN) and endosomes, thereby several lysosomal hydrolases are delivered through the endocytic pathway into lysosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22264539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Most soluble lysosomal hydrolases are sorted in the trans-Golgi network (TGN) and delivered to the lysosomes by the mannose 6-phosphate receptor (M6PR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18992238", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 331, "text": "certain soluble lysosomal hydrolases, is sorted and trafficked to the lysosomes by sortilin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18992238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the trans Golgi network (TGN) to endosomes. Recently, the multi-ligand receptor sortilin has also been implicated in this transport", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18088323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "A shortcut to the lysosome: the mannose-6-phosphate-independent pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884962", "endSection": "title" }, { "offsetInBeginSection": 787, "offsetInEndSection": 1047, "text": "several lines of evidence suggest the existence of alternative processes of lysosomal targeting. Among them, the two that are mediated by the M6P alternative receptors, lysosomal integral membrane protein (LIMP-2) and sortilin, have gained unequivocal support.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22884962", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 134, "text": "delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16787435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15078903", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 209, "text": "mannose 6-phosphate (Man-6-P) recognition marker on lysosomal hydrolases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11408573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "The delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system is mediated by selective incorporation of the receptor-hydrolase complexes into vesicular transport carriers (TCs) that are coated with clathrin and the adaptor proteins, GGA and AP-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16787435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the trans Golgi network (TGN) to endosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18088323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Mannose 6-phosphate receptors carry newly synthesized lysosomal hydrolases from the trans-Golgi network to endosomes, then return to the trans-Golgi network for another round of enzyme delivery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9247639", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1434, "text": "In this way, the M6P receptors help package the hydrolases into vesicles that bud from the trans-Golgi network to deliver their contents to endosomes that ultimately will develop into mature lysosomes, where recently-delivered hydrolases may start digesting the endocyted material.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266136", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 932, "text": "However, LS fibroblasts displayed reduced mannose 6-phosphate receptor (MPR)-mediated re-uptake of the lysosomal enzyme arylsulfatase B. In addition, endosome-to-trans Golgi network (TGN) transport of MPRs was decreased significantly, leading to higher levels of cell surface MPRs and their enrichment in enlarged, retromer-positive endosomes in OCRL-depleted HeLa cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22907655", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 1009, "text": "The M6P groups are then recognized by two independent transmembrane M6P receptors, present in the trans-Golgi network: the cation-independent M6P receptor and/or the cation-dependent M6P receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266136", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 303, "text": "Two related mannose 6-phosphate receptors (MPRs) recognize this feature in the trans Golgi network (TGN) and deliver the hydrolases to the late endosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11470415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal hydrolases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17606993", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 1008, "text": "The M6P groups are then recognized by two independent transmembrane M6P receptors, present in the trans-Golgi network: the cation-independent M6P receptor and/or the cation-dependent M6P receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the trans Golgi network (TGN) to endosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18088323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "The delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system is mediated by selective incorporation of the receptor-hydrolase complexes into vesicular transport carriers (TCs) that are coated with clathrin and the adaptor proteins, GGA and AP-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16787435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Mannose 6-phosphate receptors (MPRs) are known to be shuttled between the trans-Golgi network (TGN) and endosomes, thereby several lysosomal hydrolases are delivered through the endocytic pathway into lysosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22264539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal hydrolases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17606993", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 302, "text": "Two related mannose 6-phosphate receptors (MPRs) recognize this feature in the trans Golgi network (TGN) and deliver the hydrolases to the late endosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11470415", "endSection": "abstract" } ] }, { "body": "List the diseases that can be treated using Vedolizumab.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23394379", "http://www.ncbi.nlm.nih.gov/pubmed/21157649", "http://www.ncbi.nlm.nih.gov/pubmed/24067534", "http://www.ncbi.nlm.nih.gov/pubmed/23018007", "http://www.ncbi.nlm.nih.gov/pubmed/24918648", "http://www.ncbi.nlm.nih.gov/pubmed/23980911", "http://www.ncbi.nlm.nih.gov/pubmed/25105240", "http://www.ncbi.nlm.nih.gov/pubmed/23964933", "http://www.ncbi.nlm.nih.gov/pubmed/23964932", "http://www.ncbi.nlm.nih.gov/pubmed/23695427", "http://www.ncbi.nlm.nih.gov/pubmed/25110260", "http://www.ncbi.nlm.nih.gov/pubmed/24985716", "http://www.ncbi.nlm.nih.gov/pubmed/24899819", "http://www.ncbi.nlm.nih.gov/pubmed/24300858", "http://www.ncbi.nlm.nih.gov/pubmed/23295705", "http://www.ncbi.nlm.nih.gov/pubmed/19509315", "http://www.ncbi.nlm.nih.gov/pubmed/24246983", "http://www.ncbi.nlm.nih.gov/pubmed/22113039", "http://www.ncbi.nlm.nih.gov/pubmed/25186623", "http://www.ncbi.nlm.nih.gov/pubmed/22147460", "http://www.ncbi.nlm.nih.gov/pubmed/23083349", "http://www.ncbi.nlm.nih.gov/pubmed/23314806", "http://www.ncbi.nlm.nih.gov/pubmed/25294262", "http://www.ncbi.nlm.nih.gov/pubmed/25360311", "http://www.ncbi.nlm.nih.gov/pubmed/20594130", "http://www.ncbi.nlm.nih.gov/pubmed/24160949", "http://www.ncbi.nlm.nih.gov/pubmed/24160948", "http://www.ncbi.nlm.nih.gov/pubmed/24479980", "http://www.ncbi.nlm.nih.gov/pubmed/22762276", "http://www.ncbi.nlm.nih.gov/pubmed/23591599", "http://www.ncbi.nlm.nih.gov/pubmed/23046232", "http://www.ncbi.nlm.nih.gov/pubmed/23419117", "http://www.ncbi.nlm.nih.gov/pubmed/23718288", "http://www.ncbi.nlm.nih.gov/pubmed/23723689", "http://www.ncbi.nlm.nih.gov/pubmed/25526490", "http://www.ncbi.nlm.nih.gov/pubmed/25502899" ], "ideal_answer": [ "Ulcerative colitis and Crohn's disease are inflammatory bowel diseases that have been successfully treated with Vedolizumab, a gut-selective, anti-inflammatory monoclonal antibody." ], "exact_answer": [ [ "Ulcerative colitis" ], [ "Crohn's disease" ] ], "type": "list", "id": "5508685b4b2a315d4100000a", "snippets": [ { "offsetInBeginSection": 240, "offsetInEndSection": 411, "text": "A new gut-specific monoclonal antibody, vedolizumab, has been shown to be effective in inflammatory bowel disease, and in continued trials no patients have developed PML. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24300858", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 746, "text": "Finally, several studies were presented on new drugs with new therapeutic targets, such as vedolizumab, in the treatment of inflammatory bowel disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24160949", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 1045, "text": "We review the role of vedolizumab, a humanized antibody against the \u03b14\u03b27 - integrin, in both ulcerative colitis (UC) and Crohn's disease (CD). Results from clinical trials show that vedolizumab is effective in the induction and maintenance of remission in active CD and UC and has a very good safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23980911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Vedolizumab as induction and maintenance therapy for Crohn's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964933", "endSection": "title" }, { "offsetInBeginSection": 1895, "offsetInEndSection": 2239, "text": "NCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Vedolizumab as induction and maintenance therapy for ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964932", "endSection": "title" }, { "offsetInBeginSection": 1937, "offsetInEndSection": 2054, "text": "CONCLUSIONS: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "New and emerging treatments for ulcerative colitis: a focus on vedolizumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23723689", "endSection": "title" }, { "offsetInBeginSection": 537, "offsetInEndSection": 611, "text": " This article reviews the emerging data on the use of vedolizumab for UC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23723689", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1596, "text": " Newer treatments such as vedolizumab and tofacitinib may represent valuable future therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23718288", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1166, "text": "SUMMARY: New therapeutic targets in IBD patients who failed anti-TNF-\u03b1 therapy are urgently required, and tofacitinib, vedolizumab and ustekinumab appear to be the most promising drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23695427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: Vedolizumab, a gut-selective, anti-inflammatory monoclonal antibody, has shown preliminary efficacy in ulcerative colitis (UC) and Crohn's disease (CD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591599", "endSection": "abstract" }, { "offsetInBeginSection": 1455, "offsetInEndSection": 1709, "text": "CONCLUSION: Vedolizumab every 8 weeks for up to 78 weeks had an adverse event profile similar to that previously observed. Mean disease activity indices (partial Mayo score and Crohn's Disease Activity Index score) improved with all 3 doses investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591599", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 812, "text": "The new drugs discussed here are those that disturb lymphocyte homing to the gut (natalizumab, vedolizumab and anti-mucosal addressin cellular adhesion molecule); one that blocks interleukin (IL)-12 as well as the IL-23/T helper 17 (Th17) axis (ustekinumab) and one that blocks the signaling of multiple cytokines (tofacitinib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "Vedolizumab for Crohn's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394379", "endSection": "title" }, { "offsetInBeginSection": 396, "offsetInEndSection": 851, "text": "AREAS COVERED: This review discusses the potential role of vedolizumab, a humanised monoclonal antibody that selectively blocks lymphocyte trafficking to the gut, for the treatment of CD. All randomised placebo-controlled trials that evaluated vedolizumab for the treatment of CD were reviewed and safety and efficacy data evaluated. EXPERT OPINION: Vedolizumab is an effective and well-tolerated drug that is an important advance for the treatment of CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394379", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1510, "text": "Treatment strategies that appear particularly appealing include selective anti-integrin therapy with vedolizumab (anti-\u03b14\u03b27), etrolizumab (anti-\u03b27 antibody) and PF-00547,659 (anti-MAdCAM-1 antibody), anti-interleukin 12/23p40 therapy with ustekinumab and Janus kinase 1, 2 and 3 inhibition with toafacitinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23295705", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 933, "text": "We discuss a number of them with specific focus on vedolizumab, a monoclonal antibody directed against the alpha4beta7 integrin on lymphocytes, ustekinumab, a monoclonal antibody against the p40 subunit of interleukin-12 and interleukin-23, and tofacitinib, a small molecule targeting Janus-activated kinase. Most likely, these three agents will find their way to the market and offer significant therapeutic alternatives for the management of Crohn's disease and/or ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23314806", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 565, "text": "Natalizumab, vedolizumab, alicaforsen AJM300, rhuMAb \u03b27, CCX282-B, and PF-00547,659 are few of monoclonal antibodies that have shown high promise in trials with the potential for more attractive benefit:risk ratio than currently available therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Vedolizumab for the treatment of ulcerative colitis and Crohn's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046232", "endSection": "title" }, { "offsetInBeginSection": 781, "offsetInEndSection": 1060, "text": "Here, we discuss the current treatment options available for patients with Crohn's disease or ulcerative colitis, the history of CAM inhibitors, the current state of development of vedolizumab and its future role in inflammatory bowel disease, if approved by regulatory agencies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046232", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 725, "text": "Biological agents will probably be used earlier and more widely; new information on levels of biological agents, mucosal healing and new comparative studies will also allow these agents to be used in a more precise and personalized way. In addition to infliximab, adalimumab, natalizumab and certolizumab, other biological agents will be employed; among the first of these to be used will be ustekinumab, golimumab and vedolizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23018007", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 826, "text": "Several antibodies exist which constitute selection adhesion molecule inhibitors, including Natalizumab, MLN-0002 (Vedolizumab) and ISIS 2302 (Alicaforsen) will be discussed in this review.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22762276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Vedolizumab for the treatment of active ulcerative colitis: a randomized controlled phase 2 dose-ranging study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147460", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND: Vedolizumab is a gut-selective biologic that has shown efficacy in ulcerative colitis (UC) and Crohn's disease (CD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147460", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 955, "text": "They are anti CD4+ T cell cytokine including interleukin (IL)-12/23 and IL-17 blockers, selective anti-adhesion molecule known as natalizumab, vedolizumab and alicaforsen, T-cell proliferation inhibitor, anti-inflammatory cytokine, immune stimulator, growth factor, and mitogen-activated protein kinase inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22113039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Vedolizumab, a humanized mAb against the \u03b14\u03b27 integrin for the potential treatment of ulcerative colitis and Crohn's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21157649", "endSection": "title" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1458, "text": "Data from phase II clinical trials of vedolizumab demonstrated efficacy with an attractive safety profile, especially in ulcerative colitis. Large phase III, multicenter trials in both ulcerative colitis and Crohn's disease will provide valuable data for the ongoing development of vedolizumab, which might evolve as a new anti-inflammatory treatment option for the management of therapy-refractory patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21157649", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 1036, "text": "The development of a new specific molecule, vedolizumab, is currently under investigation in a large clinical trial. This novel specific anti-integrin drug seems to hold promise in the treatment of gut inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20594130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509315", "endSection": "title" }, { "offsetInBeginSection": 1694, "offsetInEndSection": 1932, "text": "These pharmacologic properties of vedolizumab, in conjunction with the gastrointestinal tropism of alpha(4)beta(7) integrin function, may ultimately confer an improved risk-to-benefit profile for patients with inflammatory bowel diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19509315", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1332, "text": "In the Crohn's disease study that included maintenance treatment, vedolizumab was significantly more effective at 52\u00a0weeks than placebo in both endpoints (clinical remission was the only primary endpoint in the maintenance study)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25502899", "endSection": "abstract" }, { "offsetInBeginSection": 1663, "offsetInEndSection": 1817, "text": "Vedolizumab is a useful addition to the treatment options available for patients with moderately to severely active ulcerative colitis and Crohn's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25502899", "endSection": "abstract" }, { "offsetInBeginSection": 1866, "offsetInEndSection": 2197, "text": "Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964933", "endSection": "abstract" } ] }, { "body": "Can clonidine be used to reduce agitation in children.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14977793", "http://www.ncbi.nlm.nih.gov/pubmed/17416907", "http://www.ncbi.nlm.nih.gov/pubmed/20514964", "http://www.ncbi.nlm.nih.gov/pubmed/21150631", "http://www.ncbi.nlm.nih.gov/pubmed/16677266", "http://www.ncbi.nlm.nih.gov/pubmed/18095969", "http://www.ncbi.nlm.nih.gov/pubmed/17019218", "http://www.ncbi.nlm.nih.gov/pubmed/17986032", "http://www.ncbi.nlm.nih.gov/pubmed/12173195", "http://www.ncbi.nlm.nih.gov/pubmed/16632814", "http://www.ncbi.nlm.nih.gov/pubmed/16301230", "http://www.ncbi.nlm.nih.gov/pubmed/23394604", "http://www.ncbi.nlm.nih.gov/pubmed/11473855" ], "ideal_answer": [ "Yes, clonidine is effective in prevention of post-anesthesia agitation in children." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011595", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002648", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003000" ], "type": "yesno", "id": "515df89e298dcd4e5100002f", "snippets": [ { "offsetInBeginSection": 861, "offsetInEndSection": 1089, "text": "Children receiving clonidine immediately after anesthesia induction had statistically significant improvement in postoperative agitation at the 15-minute mark (P = .096) and last score obtained (P = .095) using the Watcha scale.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394604", "endSection": "sections.0" }, { "offsetInBeginSection": 204, "offsetInEndSection": 330, "text": "Clonidine has proven to be effective in reducing the incidence of post-operative agitation at a higher dose (3 and 2 \u03bcg kg\u207b\u00b9).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150631", "endSection": "sections.0" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1396, "text": "Post-anaesthetic agitation was observed in two patients (6.6%) in group 1, eight patients (26.6%) in group 2 as compared to 12 patients (40%) in group 3 after 15 min of post-operative observation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150631", "endSection": "sections.0" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1503, "text": "The mean scores in group 1 at 15 and 30 min were significantly lower than those in group 3 (P value <0.05)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150631", "endSection": "sections.0" }, { "offsetInBeginSection": 1630, "offsetInEndSection": 1860, "text": "Caudal clonidine at a lower dose (1 \u03bcg kg\u207b\u00b9) could be effective in reducing the incidence of sevoflurane-induced emergence agitation in children undergoing urogenital and lower limb surgery without any significant adverse effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150631", "endSection": "sections.0" }, { "offsetInBeginSection": 770, "offsetInEndSection": 878, "text": "Only the 4 microg kg-1 dose of clonidine was associated with a significant reduction in emergence agitation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17416907", "endSection": "sections.0" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1001, "text": "Fewer children in the clonidine 4 microg kg-1 group displayed agitation (25%) than in the midazolam group (60%) (P=0.025).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17416907", "endSection": "sections.0" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1276, "text": "In comparison with midazolam, clonidine 4 microg kg-1 reduced sevoflurane-induced emergence agitation without increasing postoperative side-effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17416907", "endSection": "sections.0" }, { "offsetInBeginSection": 1336, "offsetInEndSection": 1450, "text": "Prophylactic use of clonidine against sevoflurane-induced agitation may represent a new and promising application.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17019218", "endSection": "sections.0" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1125, "text": "One hundred and twenty children were included in this study: 59 of whom received clonidine, and 61 placebo; 41% of those in the placebo group exhibited moderate-severe EA compared with only 22% of those in the clonidine group (P < 0.03).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16677266", "endSection": "sections.0" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1690, "text": "Findings demonstrate that i.v. clonidine administered after induction of anesthesia significantly reduces the incidence of EA in young children, but is associated with sleepiness postoperatively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16677266", "endSection": "sections.0" }, { "offsetInBeginSection": 921, "offsetInEndSection": 981, "text": "Clonidine could not prevent agitation (incidence 54%, 13/24)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16632814", "endSection": "sections.0" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1337, "text": "Clonidine 1.5 microg/kg did not differ from placebo with respect to postoperative agitation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16632814", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Clonidine is effective in treating sevoflurane-induced postanesthesia agitation in children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16301230", "endSection": "sections.0" }, { "offsetInBeginSection": 527, "offsetInEndSection": 866, "text": "Pain and discomfort scores were significantly decreased in the clonidine group; the incidence of agitation was reduced by 57% (P = 0.029) and the incidence of severe agitation by 67% (P = 0.064). Relative risks for developing agitation and severe agitation were 0.43 (95% confidence interval, 0.24-0.78) and 0.32 (0.09-1.17), respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16301230", "endSection": "sections.0" }, { "offsetInBeginSection": 867, "offsetInEndSection": 963, "text": "Clonidine produces a substantial reduction in the risk of postsevoflurane agitation in children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16301230", "endSection": "sections.0" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1103, "text": "Agitation was observed in 12 midazolam-treated and five clonidine-treated patients (P=0.05).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14977793", "endSection": "sections.0" }, { "offsetInBeginSection": 1649, "offsetInEndSection": 1745, "text": "Compared with midazolam, clonidine premedication reduced agitation during sevoflurane induction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14977793", "endSection": "sections.0" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1590, "text": "Clonidine 3 micrograms kg-1 prevented agitation after sevoflurane anaesthesia, independently of the route of administration. The effect of clonidine appears to be dose-dependent, as an epidural dose of 1 microgram kg-1 failed to reduce it.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12173195", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Clonidine prevents sevoflurane-induced agitation in children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11473855", "endSection": "title" }, { "offsetInBeginSection": 482, "offsetInEndSection": 563, "text": "In 16 placebo and 2 clonidine-treated patients agitation was observed (P < 0.001)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11473855", "endSection": "sections.0" }, { "offsetInBeginSection": 565, "offsetInEndSection": 723, "text": "In 6 patients of the Placebo group, agitation was graded as severe, whereas none of the patients in the Clonidine group developed severe agitation (P = 0.02).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11473855", "endSection": "sections.0" }, { "offsetInBeginSection": 857, "offsetInEndSection": 944, "text": "We conclude that clonidine effectively prevents agitation after sevoflurane anesthesia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11473855", "endSection": "sections.0" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1239, "text": "Clonidine 2 microg/kg IV after anesthetic induction effectively reduces the incidence of agitation without resulting in clinically relevant bradycardia and hypotension.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11473855", "endSection": "sections.0" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1730, "text": "Children receiving clonidine prior to undergoing strabismus surgery have a small but noticeable reduction in postoperative agitation, stay slightly longer in the post-anesthesia care unit, and have higher rates of parent satisfaction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394604", "endSection": "sections.0" }, { "offsetInBeginSection": 147, "offsetInEndSection": 599, "text": "We report three cases of preoperative use of intranasal clonidine in pediatric patients, all for different indications. One patient was treated for preoperative agitation and hallucinations associated with oral midazolam. One patient was given clonidine as a premedicant. The third patient was treated for preoperative agitation and hypertension. All three patients had subjective resolution of indicated symptoms and none experienced adverse outcomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18095969", "endSection": "sections.0" }, { "offsetInBeginSection": 389, "offsetInEndSection": 532, "text": "Oral or intravenous clonidine has been successfully used for the prevention of sevoflurane-induced agitation during emergence from anaesthesia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17019218", "endSection": "sections.0" } ] }, { "body": "Which value of nuchal translucency thickness is set as the threshold for high-risk for Down Syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18461550", "http://www.ncbi.nlm.nih.gov/pubmed/19416569", "http://www.ncbi.nlm.nih.gov/pubmed/16912493", "http://www.ncbi.nlm.nih.gov/pubmed/18726925", "http://www.ncbi.nlm.nih.gov/pubmed/9471429" ], "ideal_answer": [ "NT is physiological for a measurement < 3 mm but the incidence of chromosomal abnormalities (essentially trisomies 21, 18 and 13) increases when NT > or = 3 mm. As women aged, this upper NT threshold value changed according to gestational age. In women aged 35 to 37 years, combined prenatal screening was always positive when NT exceeded 2.8 mm, 3.0 mm, and 3.4 mm at 11, 12, and 13 weeks of gestation, respectively." ], "exact_answer": [ "3mm" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004314", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018566", "http://www.disease-ontology.org/api/metadata/DOID:14250", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048208" ], "type": "factoid", "id": "53592c1e9a4572de6f000002", "snippets": [ { "offsetInBeginSection": 511, "offsetInEndSection": 610, "text": "Combined prenatal screening was always positive for Down syndrome when NT thickness exceeded 4.0 mm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19416569", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 867, "text": "In women aged 35 to 37 years, combined prenatal screening was always positive when NT exceeded 2.8 mm, 3.0 mm, and 3.4 mm at 11, 12, and 13 weeks of gestation, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19416569", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 618, "text": "NT is physiological for a measurement < 3 mm but the incidence of chromosomal abnormalities (essentially trisomies 21, 18 and 13) increases when NT > or = 3 mm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9471429", "endSection": "abstract" } ] }, { "body": "Does ventriculoperitoneal shunt improve normal pressure hydrocephalus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23640238", "http://www.ncbi.nlm.nih.gov/pubmed/10586442", "http://www.ncbi.nlm.nih.gov/pubmed/17226742", "http://www.ncbi.nlm.nih.gov/pubmed/8747951", "http://www.ncbi.nlm.nih.gov/pubmed/2696283", "http://www.ncbi.nlm.nih.gov/pubmed/21993525" ], 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"yesno", "id": "532627d0d6d3ac6a34000001", "snippets": [ { "offsetInBeginSection": 1573, "offsetInEndSection": 1754, "text": "Clinical improvement depends not only on the capability to restore the cerebrospinal fluid dynamic, but also on the ability of cerebral parenchyma to recover the metabolic function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23640238", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 842, "text": " After shunting, the global CMRglu significantly increased (2.95 \u00b1 0.44 vs 4.38 \u00b1 0.68, p = 10(-7)) in all INPH patients with a mean percentage value of 48.7%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993525", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1786, "text": "Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of \"neuronal plasticity\" and for the cells' reactivity in order to recover their metabolic function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993525", "endSection": "abstract" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1502, "text": "Outcome of shunting in INPH is most often successful when patients are accurately diagnosed, suitably evaluated for surgical candidacy, and managed carefully throughout the preoperative, surgical, and postoperative periods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17226742", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1064, "text": "The decision to perform the only efficient procedure, i.e., a ventricular shunt operation, depends upon a number of established arguments in favor of that procedure. Clinical improvement, which is often spectacular, can then confirm the diagnosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10586442", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1297, "text": "During the 1st postoperative year, there was improvement in the condition of 22 patients (96%) who had received a ventricular shunt; 21 of these patients (91%) remained improved until death or for at least 5 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8747951", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1392, "text": "Shunt treatment showed an effect on cognitive functions of distractibility of attention and motor speed, but not on intelligence of memory. Three patients deteriorated, eleven remained stable and sixteen showed significant improvement on psychological tests, mainly those for attention, motor speed and memory, but rarely did any improvement of intelligence occur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2696283", "endSection": "abstract" } ] }, { "body": "Does Serca2a bind PLN in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20484118", "http://www.ncbi.nlm.nih.gov/pubmed/12763867", "http://www.ncbi.nlm.nih.gov/pubmed/9182523", "http://www.ncbi.nlm.nih.gov/pubmed/17515962", "http://www.ncbi.nlm.nih.gov/pubmed/11854448", "http://www.ncbi.nlm.nih.gov/pubmed/12424227", "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "http://www.ncbi.nlm.nih.gov/pubmed/22693651", "http://www.ncbi.nlm.nih.gov/pubmed/12589804", "http://www.ncbi.nlm.nih.gov/pubmed/8702967", "http://www.ncbi.nlm.nih.gov/pubmed/9603928", "http://www.ncbi.nlm.nih.gov/pubmed/17241641", "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "http://www.ncbi.nlm.nih.gov/pubmed/22129433", "http://www.ncbi.nlm.nih.gov/pubmed/22659291" ], "ideal_answer": [ "Yes, Serca2a bind PLN in the heart." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053498", "http://www.uniprot.org/uniprot/PPLA_HUMAN" ], "type": "yesno", "id": "51680b05298dcd4e51000064", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The human phospholamban Arg14-deletion mutant localizes to plasma membrane and interacts with the Na/K-ATPase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "endSection": "title" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1338, "text": "Moreover, PLN-R14Del did not co-immunoprecipitate with SERCA2a (as did WT-PLN),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155237", "endSection": "sections.0" }, { "offsetInBeginSection": 441, "offsetInEndSection": 695, "text": "n this review, we attempted to highlight the functional significance of PLN in vertebrate cardiac physiology. We will refer to the huge literature on mammals in order to describe the molecular characteristics of this protein, its interaction with SERCA2a", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22129433", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "There is clear evidence for direct regulatory protein-protein interactions between phospholamban (PLN) and the Ca2+-ATPase of cardiac sarcoplasmic reticulum (SERCA2a) in cytoplasmic domains", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8702967", "endSection": "sections.0" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1447, "text": "These results suggest that PLN modulates the apparent Ca2+ affinity of SERCA2a through intramembrane interactions, which are disrupted at long range and in concert with disruption of the well characterized cytoplasmic interactions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8702967", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Phospholamban (PLN), a homopentameric, integral membrane protein, reversibly inhibits cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity through intramembrane interactions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182523", "endSection": "sections.0" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1493, "text": "The concentration of this inhibited complex is determined by the dissociation constant for the PLN pentamer (which is mutation-sensitive) and by the dissociation constant for the PLN/SERCA2a heterodimer (which is likely to be mutation-sensitive).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9182523", "endSection": "sections.0" }, { "offsetInBeginSection": 1439, "offsetInEndSection": 1634, "text": "These results support the proposal that PLN inhibition of SERCA2a involves, first, depolymerization of PLN and, second, the formation of inhibitory interactions between monomeric PLN and SERCA2a.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9603928", "endSection": "sections.0" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1162, "text": "SLN and PLN appear to bind to the same regulatory site in SERCA. However, in a ternary complex, PLN occupies the regulatory site and SLN binds to the exposed side of PLN and to SERCA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12763867", "endSection": "sections.0" }, { "offsetInBeginSection": 595, "offsetInEndSection": 707, "text": "Cellular and biochemical studies revealed that, unlike wild-type PLN, PLN(R9C) did not directly inhibit SERCA2a.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12610310", "endSection": "sections.0" }, { "offsetInBeginSection": 789, "offsetInEndSection": 997, "text": ". Conversely, using anti-SERCA2a antibody, both PLN and acylphosphatase were co-immunoprecipitated with SERCA2a, and the PLN amount in the precipitate decreased with increasing acylphosphatase concentrations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12589804", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Reconstitution of the cytoplasmic interaction between phospholamban and Ca(2+)-ATPase of cardiac sarcoplasmic reticulum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854448", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Phospholamban (PLN) reversibly inhibits the Ca(2+)-ATPase of cardiac sarcoplasmic reticulum (SERCA2a) through a direct protein-protein interaction, playing a pivotal role in the regulation of intracellular Ca(2+) in heart muscle cells.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854448", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Phospholamban (PLN) is a key regulator of Ca(2+) homeostasis and contractility in the heart. Its regulatory effects are mediated through its interaction with the sarcoplasmic reticulum Ca(2+)-ATPase, (SERCA2a), resulting in alterations of its Ca(2+)-affinity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241641", "endSection": "sections.0" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1284, "text": "In a co-immunoprecipitation of PLN with SERCA2a, the physical interaction between the two proteins was increased in PUGNAc-treated cardiomyocytes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20484118", "endSection": "sections.0" } ] }, { "body": "What is the function of the spliceosome complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17574835", "http://www.ncbi.nlm.nih.gov/pubmed/24788092", "http://www.ncbi.nlm.nih.gov/pubmed/18025254", "http://www.ncbi.nlm.nih.gov/pubmed/22430224", "http://www.ncbi.nlm.nih.gov/pubmed/24047207" ], "ideal_answer": [ "The excision of introns from nascent eukaryotic transcripts is catalyzed by the spliceosome, a highly complex and dynamic macromolecular machine composed of RNA and protein." ], "exact_answer": [ "The excision of introns from nascent eukaryotic transcripts is catalyzed by the spliceosome." ], "type": "factoid", "id": "56f553e309dd18d46b000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The spliceosome machinery is composed of multimeric protein complexes that generate a diverse repertoire of mRNA through coordinated splicing of heteronuclear RNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24788092", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 221, "text": "Splicing and alternate splicing are the two key biological processes that result in the generation of diverse transcript and protein isoforms in Plasmodium falciparum as well as in other eukaryotic organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24047207", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 212, "text": " Spliceosome assembly belongs to the key processes that enable splicing of mRNA and modulate alternative splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The excision of introns from nascent eukaryotic transcripts is catalyzed by the spliceosome, a highly complex and dynamic macromolecular machine composed of RNA and protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025254", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 415, "text": "Recent advances have begun to provide exciting new insights into the dynamic interactions that govern the function of the spliceosome, the multi-megadalton complex that performs splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574835", "endSection": "abstract" } ] }, { "body": "Is there any role for long noncoding RNAs in adipogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23401553" ], "ideal_answer": [ "Yes. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and CCAAT/enhancer-binding protein \u03b1 (CEBP\u03b1). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, numerous lncRNAs are functionally required for proper adipogenesis." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050155", "http://amigo.geneontology.org/amigo/term/GO:0060612", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050156" ], "type": "yesno", "id": "56d1d56b67f0cb3d66000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Long noncoding RNAs regulate adipogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401553", "endSection": "title" }, { "offsetInBeginSection": 366, "offsetInEndSection": 1008, "text": "Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and CCAAT/enhancer-binding protein \u03b1 (CEBP\u03b1). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401553", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 797, "text": "Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and CCAAT/enhancer-binding protein \u03b1 (CEBP\u03b1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401553", "endSection": "abstract" } ] }, { "body": "Which genes code for the alpha subunit of the DNA polymerase III in most Firmicutes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20403380", "http://www.ncbi.nlm.nih.gov/pubmed/24899249", "http://www.ncbi.nlm.nih.gov/pubmed/16083981", "http://www.ncbi.nlm.nih.gov/pubmed/22333191", "http://www.ncbi.nlm.nih.gov/pubmed/2499883", "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "http://www.ncbi.nlm.nih.gov/pubmed/24062730" ], "ideal_answer": [ "Bacterial DNA polymerase III is the primary complex of DNA replication. In most Firmicutes, which are low-GC, gram-positive bacteria, the alpha subunit of their DNA polymerase III is encoded by polC and dnaE. DnaE is widely conserved in most bacteria, while PolC is present mainly in Firmicutes clade." ], "exact_answer": [ [ "dnaE" ], [ "polC" ] ], "concepts": [ "http://www.uniprot.org/uniprot/DPOL3_SULSO", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004259", "http://www.uniprot.org/uniprot/DPOL3_SULSH", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003887" ], "type": "list", "id": "553fac39c6a5098552000001", "snippets": [ { "offsetInBeginSection": 971, "offsetInEndSection": 1070, "text": "PolC co-evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22333191", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 189, "text": "Bacterial genomes displaying a strong bias between the leading and the lagging strand of DNA replication encode two DNA polymerases III, DnaE and PolC, rather than a single one.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22333191", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 643, "text": "SGD, PAS, and polC are all features associated with a group of low-GC, gram-positive bacteria (Firmicutes)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 781, "text": "PAS is a characteristic of organisms with a heterodimeric DNA polymerase III alpha-subunit constituted by polC and dnaE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 357, "text": "Bacterial DNA polymerase III, the primary complex of DNA replication, consists of PolC and DnaE. PolC is conserved in Gram-positive bacteria, especially in the Firmicutes with low GC content, whereas DnaE is widely conserved in most Gram-negative and Gram-positive bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24062730", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1309, "text": "PolC-PolE DNA polymerases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20403380", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 838, "text": "We conclude that PAS is a characteristic of organisms with a heterodimeric DNA polymerase III alpha-subunit constituted by polC and dnaE, which may play a direct role in the maintenance of SGD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 643, "text": "Furthermore, SGD, PAS, and polC are all features associated with a group of low-GC, gram-positive bacteria (Firmicutes)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532183", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1104, "text": "In contrast, PolC co-evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade, suggesting at least two origins for the degradosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22333191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "A method for the construction of in frame substitutions in operons: deletion of the essential Escherichia coli holB gene coding for a subunit of the DNA polymerase III holoenzyme.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16083981", "endSection": "title" } ] }, { "body": "Is there any research that relates the function of Notch Signaling with Alzheimer Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22122056", "http://www.ncbi.nlm.nih.gov/pubmed/23570941", "http://www.ncbi.nlm.nih.gov/pubmed/23197721", "http://www.ncbi.nlm.nih.gov/pubmed/24099003", "http://www.ncbi.nlm.nih.gov/pubmed/21768095", "http://www.ncbi.nlm.nih.gov/pubmed/22792182", "http://www.ncbi.nlm.nih.gov/pubmed/21206757", "http://www.ncbi.nlm.nih.gov/pubmed/19881909" ], "ideal_answer": [ "Notch signaling is an evolutionarily conserved pathway, which is fundamental for neuronal development and specification. In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023582", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051880", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0023052" ], "type": "yesno", "id": "532bf6f2d6d3ac6a34000015", "snippets": [ { "offsetInBeginSection": 232, "offsetInEndSection": 744, "text": "RIP regulates signaling pathways by abrogating or releasing signaling molecules. Since the discovery, already >15 years ago, of its catalytic component, presenilin, and even much earlier with the identification of amyloid precursor protein as its first substrate, \u03b3-secretase has been commonly associated with Alzheimer's disease. However, starting with Notch and thereafter a continuously increasing number of novel substrates, \u03b3-secretase is becoming linked to an equally broader range of biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24099003", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 618, "text": "In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23570941", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 616, "text": "Along with \u03b2-secretase, this enzyme produces the amyloid \u03b2-protein of Alzheimer's disease (AD) from the amyloid \u03b2-protein precursor. Because of its key role in the pathogenesis of AD, \u03b3-secretase has been a prime target for drug discovery, and many inhibitors of this protease have been developed. The therapeutic potential of these inhibitors is virtually negated by the fact that \u03b3-secretase is an essential part of the Notch signaling pathway, rendering the compounds unacceptably toxic upon chronic exposure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122056", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 1057, "text": "High physiological concentrations of A\u03b2 monomer induced angiogenesis by a conserved mechanism that blocks \u03b3-secretase processing of a Notch intermediate, NEXT, and reduces the expression of downstream Notch target genes. Our findings allude to an integration of signaling pathways that utilize \u03b3-secretase activity, which may have significant implications for our understanding of Alzheimer's pathogenesis vis-\u00e0-vis vascular changes that set the stage for ensuing neurodegeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22792182", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 767, "text": "Aggregated forms of A\u03b2 have a pathogenic role in Alzheimer disease and, thus, reducing the A\u03b2 levels by inhibiting \u03b3-secretase is a possible treatment strategy for Alzheimer disease. Regrettably, clinical trials have shown that inhibition of \u03b3-secretase results in Notch-related side effects. Therefore, it is of great importance to find ways to inhibit amyloid precursor protein (APP) processing without disturbing vital signaling pathways such as Notch. Nicastrin (Nct) is part of the \u03b3-secretase complex and has been proposed to be involved in substrate recognition and selection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21768095", "endSection": "abstract" } ] }, { "body": "Describe the known functions for the prothymosin alpha c-terminal peptide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18856068", "http://www.ncbi.nlm.nih.gov/pubmed/17929838", "http://www.ncbi.nlm.nih.gov/pubmed/2209614", "http://www.ncbi.nlm.nih.gov/pubmed/11744386", "http://www.ncbi.nlm.nih.gov/pubmed/18976813", "http://www.ncbi.nlm.nih.gov/pubmed/18645619", "http://www.ncbi.nlm.nih.gov/pubmed/23201434", "http://www.ncbi.nlm.nih.gov/pubmed/16453152", "http://www.ncbi.nlm.nih.gov/pubmed/20467443" ], "triples": [ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423651354534004", "o": "Prothymosin alpha" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7615967", "o": "Prothymosin Alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423945504C3900F", "o": "Prothymosin alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_433356565638006", "o": "Prothymosin alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_443057525431006", "o": "Prothymosin alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503036343534001F", "o": "Prothymosin alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513135323032007", "o": "Prothymosin alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513633343532007", "o": "Prothymosin-alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503031323532007", "o": "Prothymosin alpha" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513239323836007", "o": "Prothymosin alpha" } ], "ideal_answer": [ "Prothymosin alpha (ProT\u03b1) (encoded in human by the PTMA gene) is a ubiquitous, highly acidic nuclear polypeptide. During early apoptosis, proT\u03b1 is cleaved by activated caspase-3, with a primary attach site being D99, close to its carboxyl-terminus. The role of the cleaved decapeptide -- proT\u03b1(100-109) -- is not fully understood. proT\u03b1(100-109), which contains the nuclear localization signal (NLS) for ProT\u03b1, has been demonstrated to have immunostimulatory properties, such as to stimulate lymphocytes and neutrophils and induce dendritic cell maturation." ], "concepts": [ "http://www.uniprot.org/uniprot/PTMA_BOVIN", "http://www.uniprot.org/uniprot/PTMA_RANES", "http://www.uniprot.org/uniprot/PTMAB_XENLA", "http://www.uniprot.org/uniprot/PTMA_HUMAN", "http://www.uniprot.org/uniprot/PTMA_PONAB", "http://www.uniprot.org/uniprot/PTMA_MOUSE", "http://www.uniprot.org/uniprot/PTMAA_XENLA", "http://www.uniprot.org/uniprot/PTMAB_DANRE", "http://www.uniprot.org/uniprot/PTMA_RAT", "http://www.uniprot.org/uniprot/PTMAA_DANRE" ], "type": "summary", "id": "51be03c4047fa84d1d000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The C-terminal decapeptide of prothymosin \u03b1 is responsible for its stimulatory effect on the functions of human neutrophils in vitro", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23201434", "endSection": "title" }, { "offsetInBeginSection": 372, "offsetInEndSection": 676, "text": "In this study, we investigated the ability of the immunoreactive fragment of the polypeptide prothymosin alpha (proT\u03b1), i.e., the decapeptide proT\u03b1(100-109), to enhance the functions of neutrophils isolated from the peripheral blood of breast cancer patients in comparison with those from healthy donors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23201434", "endSection": "sections.0" }, { "offsetInBeginSection": 1473, "offsetInEndSection": 1590, "text": "Our results suggest that proT\u03b1(100-109) activates neutrophils, particularly those derived from breast cancer patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23201434", "endSection": "sections.0" }, { "offsetInBeginSection": 577, "offsetInEndSection": 707, "text": "The Ca\u00b2(+)-dependent interaction between ProT\u03b1 and S100A13 was found to require the C-terminal peptide sequences of both proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20467443", "endSection": "sections.0" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1027, "text": "When cells were administered apoptogenic compounds, ProT\u03b1 was cleaved by caspase-3 to generate a C-terminal peptide-deficient fragment, which lacks the nuclear localization signal (NLS).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20467443", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Prothymosin alpha immunoactive carboxyl-terminal peptide TKKQKTDEDD stimulates lymphocyte reactions, induces dendritic cell maturation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18976813", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Prothymosin alpha (ProTalpha) is a small acidic polypeptide with important immunostimulatory properties, which we have previously shown to be exerted by its carboxyl (C)-terminus", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18976813", "endSection": "sections.0" }, { "offsetInBeginSection": 288, "offsetInEndSection": 838, "text": "Here, we assayed the activity of synthetic peptides homologous to ProTalpha's C-terminus to stimulate lymphocyte functions, in particular natural killer cell cytotoxicity of peripheral blood mononuclear cells isolated from healthy donors. A synthetic decapeptide TKKQKTDEDD was identified as the most potent lymphocyte stimulator. The activity of this peptide was sequence-specific and comparable to that of the intact molecule, suggesting that ProTalpha's immunoactive segment encompasses the nuclear localization signal sequence of the polypeptide.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18976813", "endSection": "sections.0" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1918, "text": "These data, in conjunction with reports showing that the peptide TKKQKTDEDD is generated in vivo upon caspase-cleavage of ProTalpha during apoptosis, strengthen our hypothesis that immune response stimulation by ProTalpha is in principle exerted via its bioactive C-terminal decapaptide, which can acquire a sequence-specific beta-sheet conformation and induce DC maturation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18976813", "endSection": "sections.0" }, { "offsetInBeginSection": 421, "offsetInEndSection": 763, "text": "Ability to stimulate p53-dependent transcription was lost by C-terminal mutants of prothymosin alpha with impaired nuclear accumulation, but not by N-terminal deletion mutants and by the double mutant of prothymosin alpha with impaired ability to bind Keap1, suggesting that prothymosinalpha-Keap1 interaction is dispensable for p53 response.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18856068", "endSection": "sections.0" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1097, "text": "We found that zinc binding causes partial folding of the C-terminal half of ProTalpha, especially the Glu-rich region", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17929838", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The immunologically active site of prothymosin alpha is located at the carboxy-terminus of the polypeptide.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16453152", "endSection": "title" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1303, "text": ". ProTalpha(89-102) and proTalpha(103-109) significantly fortified healthy donor-lymphocytes' immune responses to levels comparable to those induced by intact proTalpha. These effects were more pronounced in cancer patients, where peptides proTalpha(89-102) and proTalpha(103-109) partly, however significantly, restored the depressed AMLR and cytolytic ability of PBMC, by simulating the biological activity exerted by intact proTalpha.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16453152", "endSection": "sections.0" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1528, "text": "This is the first report showing that proTalpha's immunomodulating activity can be substituted by its C-terminal peptide(s)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16453152", "endSection": "sections.0" }, { "offsetInBeginSection": 677, "offsetInEndSection": 886, "text": "The peptide (1-88) of calf prothymosin alpha is shown not to accumulate in the Xenopus nucleus, demonstrating that the C-terminal 21 residues, which include a KKQK sequence, are required for nuclear migration.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2209614", "endSection": "sections.0" }, { "offsetInBeginSection": 261, "offsetInEndSection": 417, "text": "fProt-alpha contains 28 aspartic and 25 glutamic acid residues and presents the typical basic KKQK amino acid sequence in the close carboxyl terminal region", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11744386", "endSection": "sections.0" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1529, "text": "This is the first report showing that proTalpha's immunomodulating activity can be substituted by its C-terminal peptide(s).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16453152", "endSection": "sections.0" } ] }, { "body": "Was modafinil tested for schizophrenia treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21412225", "http://www.ncbi.nlm.nih.gov/pubmed/15085092", "http://www.ncbi.nlm.nih.gov/pubmed/19572020", "http://www.ncbi.nlm.nih.gov/pubmed/23983964", "http://www.ncbi.nlm.nih.gov/pubmed/17151173", "http://www.ncbi.nlm.nih.gov/pubmed/22820555", "http://www.ncbi.nlm.nih.gov/pubmed/22820554", "http://www.ncbi.nlm.nih.gov/pubmed/23938173", "http://www.ncbi.nlm.nih.gov/pubmed/24964814", "http://www.ncbi.nlm.nih.gov/pubmed/20810469", "http://www.ncbi.nlm.nih.gov/pubmed/19689921", "http://www.ncbi.nlm.nih.gov/pubmed/17503979", "http://www.ncbi.nlm.nih.gov/pubmed/25306261", "http://www.ncbi.nlm.nih.gov/pubmed/18516718", "http://www.ncbi.nlm.nih.gov/pubmed/17712350", "http://www.ncbi.nlm.nih.gov/pubmed/20653641", "http://www.ncbi.nlm.nih.gov/pubmed/16013898", "http://www.ncbi.nlm.nih.gov/pubmed/17077439", "http://www.ncbi.nlm.nih.gov/pubmed/19914296", "http://www.ncbi.nlm.nih.gov/pubmed/16634707", "http://www.ncbi.nlm.nih.gov/pubmed/18729534", "http://www.ncbi.nlm.nih.gov/pubmed/21947320", "http://www.ncbi.nlm.nih.gov/pubmed/16965205", "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "http://www.ncbi.nlm.nih.gov/pubmed/18392753", "http://www.ncbi.nlm.nih.gov/pubmed/21565464", "http://www.ncbi.nlm.nih.gov/pubmed/17634412", "http://www.ncbi.nlm.nih.gov/pubmed/15994572", "http://www.ncbi.nlm.nih.gov/pubmed/21109234", "http://www.ncbi.nlm.nih.gov/pubmed/21909634", "http://www.ncbi.nlm.nih.gov/pubmed/15090936" ], "ideal_answer": [ "Yes. Modafinil has been shown to improve attention, memory, executive function and antipsychotic-induced parkinsonism in patients with schizophrenia. However, some authors have failed to demonstrate beneficial action of modafinil for schizophrenia." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4259639", "http://www.disease-ontology.org/api/metadata/DOID:5419" ], "type": "yesno", "id": "54fc845e6ea36a810c000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23938173", "endSection": "title" }, { "offsetInBeginSection": 1382, "offsetInEndSection": 1565, "text": "CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23938173", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 1027, "text": "A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements. Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "BACKGROUND: Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964", "endSection": "title" }, { "offsetInBeginSection": 224, "offsetInEndSection": 487, "text": "It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1235, "text": "Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 2139, "text": "In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to enhance cognitive function, attenuate fatigue, enhance activity, improve negative symptoms and reduce weight in patients with schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "RATIONAL: In recent years, evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia, especially for the negative and cognitive symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320", "endSection": "abstract" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1405, "text": "CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 324, "text": "Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21909634", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1261, "text": "CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21565464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Modafinil (2-((diphenylmethyl)sulfinyl)acetamide) is described as an atypical stimulant and is a putative cognition enhancer for schizophrenia, but the precise mechanisms of action remain unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21412225", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 319, "text": "Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109234", "endSection": "abstract" }, { "offsetInBeginSection": 1613, "offsetInEndSection": 1900, "text": "CONCLUSIONS: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20653641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19914296", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1241, "text": "CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19689921", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 316, "text": "We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19572020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 456, "text": "OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1648, "text": "RESULTS: One of 4 reviewed studies found a significant effect of modafinil as an alerting agent for antipsychotic-induced fatigue and sedation. Neither of 2 reviewed studies found modafinil to improve negative symptoms of schizophrenia. Three of 6 reviewed studies showed that modafinil may improve short-term memory, attention, and the ability to shift mental sets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 1972, "offsetInEndSection": 2439, "text": "CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 2743, "offsetInEndSection": 2883, "text": "Hence, before prescribing modafinil to a schizophrenia patient, the possible risks and benefits of each particular case should be evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 2211, "offsetInEndSection": 2506, "text": "Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18729534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "RATIONALE: The wake-promoting agent modafinil selectively improves neuropsychological task performance in healthy volunteers, in adults with attention deficit hyperactivity disorder (ADHD) and in schizophrenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18516718", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 394, "text": "Recently, however, modafinil has been shown to improve attentional set-shifting performance in patients with schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18392753", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 462, "text": "In addition, modafinil shows initial promise for a variety of off-label indications in psychiatry, including treatment-resistant depression, attention-deficit/hyperactivity disorder, and schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17712350", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 396, "text": "There is increasing interest in the use of modafinil to improve cognition in schizophrenia as well as in other disorders such as attention-deficit/hyperactivity disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17634412", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 702, "text": "Initial findings indicate that modafinil may lead to better executive functioning and attentional performance in patients with schizophrenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17634412", "endSection": "abstract" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1701, "text": "CONCLUSIONS: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17503979", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1059, "text": "CONCLUSIONS: Modafinil did not improve cognitive control in all schizophrenia patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17151173", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 492, "text": ". These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17077439", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1784, "text": "One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965205", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 743, "text": " Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16634707", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 887, "text": "In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16013898", "endSection": "abstract" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1136, "text": "CONCLUSIONS: Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15994572", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 873, "text": "Modafinil significantly improved overall clinical condition, with 64% and 82% of patients rated as clinically improved at week 4 by a blinded clinician and the investigator respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1068, "text": "Modafinil significantly improved fatigue (P = 0.025, week 3) and tended to improve cognitive functioning scores. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1597, "text": "Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 807, "text": "Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15085092", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1407, "text": "Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15085092", "endSection": "abstract" }, { "offsetInBeginSection": 1887, "offsetInEndSection": 2340, "text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1339, "text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 485, "text": " It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983964", "endSection": "abstract" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1404, "text": "CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 455, "text": "OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 1971, "offsetInEndSection": 2437, "text": "CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1596, "text": "Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15090936", "endSection": "abstract" }, { "offsetInBeginSection": 1909, "offsetInEndSection": 2361, "text": "While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026265", "endSection": "abstract" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1356, "text": "The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21947320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820554", "endSection": "abstract" } ] }, { "body": "What is the role of the Ada O6-alkylguanine alkyltransferase in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10101186", "http://www.ncbi.nlm.nih.gov/pubmed/9079656", "http://www.ncbi.nlm.nih.gov/pubmed/1747932", "http://www.ncbi.nlm.nih.gov/pubmed/7695814", "http://www.ncbi.nlm.nih.gov/pubmed/9484244", "http://www.ncbi.nlm.nih.gov/pubmed/3526284", "http://www.ncbi.nlm.nih.gov/pubmed/9366274", "http://www.ncbi.nlm.nih.gov/pubmed/8512805", "http://www.ncbi.nlm.nih.gov/pubmed/8152424", "http://www.ncbi.nlm.nih.gov/pubmed/3887409", "http://www.ncbi.nlm.nih.gov/pubmed/1520330", "http://www.ncbi.nlm.nih.gov/pubmed/8195077", "http://www.ncbi.nlm.nih.gov/pubmed/8519412", "http://www.ncbi.nlm.nih.gov/pubmed/7662116", "http://www.ncbi.nlm.nih.gov/pubmed/9717173", "http://www.ncbi.nlm.nih.gov/pubmed/7634390", "http://www.ncbi.nlm.nih.gov/pubmed/2105461" ], "ideal_answer": [ "The Ada O6-methylguanine-DNA methyltransferase is a multifunctional protein, product of the ada gene. Ada functions in DNA repair by direct dealkylation of alkylated DNA lesions, such as the toxic, mutagenic and carcinogenic O6-alkylguanine (O6-AlkG) and O4-alkylthymine (O4-AlkT) which are restored to guanine and thymine. Ada accepts stoichiometrically the alkyl group from O6-alkylguanine in DNA at the Cys-321 residue and from alkyl phosphotriester at the Cys-69 residue. When methylated at Cys-69, Ada becomes a transcriptional activator of the genes in the ada regulon, including its own. The ada gene controls the inducible resistance to alkylation mutagenesis and killing (the adaptive response). Ada alkyltransferase (ATase) is induced by exposure to low doses of methylating agents. During exponential growth, Ada removes lesions responsible for G:C to A:T transitions and G:C to C:G transversions, while in stationary populations it removes lesions causing G:C to A:T and A:T to G:C transitions, and G:C to C:G, A:T to C:G, and A:T to T:A transversions. Thus, Ada protein acts both as a positive regulator of the ada response and as a DNA repair enzyme." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003908", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019853", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009617", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032132" ], "type": "summary", "id": "5541ffc3472cfd8617000004", "snippets": [ { "offsetInBeginSection": 4, "offsetInEndSection": 135, "text": "multifunctional 39 kDa Escherichia coli Ada protein (O6-methylguanine-DNA methyltransferase) (EC 2.1.1.63), product of the ada gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9484244", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 693, "text": "The Ada protein accepts stoichiometrically the alkyl group from O6-alkylguanine in DNA at the Cys-321 residue and from alkyl phosphotriester at the Cys-69 residue. This protein functions in DNA repair by direct dealkylation of mutagenic O6-alkylguanine. The protein methylated at Cys-69 becomes a transcriptional activator of the genes in the ada regulon, including its own. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9484244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "O6-Alkylguanine DNA-alkyltransferase (ATase) repairs toxic, mutagenic and carcinogenic O6-alkylguanine (O6-alkG) lesions in DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9366274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "O6-Methylguanine is removed from DNA via the transfer of the methyl group to a cysteine acceptor site present in the DNA repair protein O6-alkylguanine-DNA alkyltransferase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9079656", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1609, "text": "DNA repair by O6-alkylguanine-DNA alkyltransferases plays a major role in removing lesions responsible for GC-->AT transitions induced by CCNU, influencing their ultimate distribution with respect to sequence context.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8519412", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 812, "text": "alkyltransferase (ATase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7662116", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1319, "text": "the ada ATase induced by exposure to low doses of a methylating agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7662116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The Escherichia coli Ada and Ogt DNA methyltransferases (MTases) are known to transfer simple alkyl groups from O6-alkylguanine and O4-alkylthymine, directly restoring these alkylated DNA lesions to guanine and thymine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8195077", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 806, "text": "During exponential growth, the spontaneous rate of G:C to A:T transitions and G:C to C:G transversions was elevated about fourfold in ada ogt double mutant versus wild-type E. coli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8195077", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 1125, "text": "compared with the wild type, stationary populations of the MTase-deficient E. coli (under lactose selection) displayed increased G:C to A:T and A:T to G:C transitions (10- and 3-fold, respectively) and increased G:C to C:G, A:T to C:G, and A:T to T:A transversions (10-, 2.5-, and 1.7-fold, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8195077", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 402, "text": "ATases are able to repair O6-alkylguanine (O6-AlkG) and O4-alkylthymine (O4-AlkT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8512805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The inducible resistance to alkylation mutagenesis and killing in Escherichia coli (the adaptive response) is controlled by the ada gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3887409", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 355, "text": "The Ada protein acts both as a positive regulator of the response and as a DNA repair enzyme, correcting premutagenic O6-alkylguanine in DNA by suicidal transfer of the alkyl group to one of its own cysteine residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3887409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Forward mutations induced by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the lacl gene of Escherichia coli were recovered from bacteria proficient (Ogt+ Ada+) and deficient (Ogt- Ada-) in O6-alkylguanine-DNA alkyltransferase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8519412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Spontaneous mutagenesis in O6-alkylguanine-DNA alkyltransferase-proficient and -deficient (ada ogt mutants) Escherichia coli was studied in two ways: in bacteria growing in nonselective liquid medium and in bacteria resting on selective agar plates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9717173", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 406, "text": "We now show by Southern analysis that the mutation involves a gross deletion covering at least the ogt and fnr genes and that no O6-alkylguanine-DNA-alkyltransferase activity is present in cell-free extracts of an ada::Tn10 derivative of these bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8152424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "O6-Alkylguanine DNA-alkyltransferase (ATase) repairs toxic, mutagenic and carcinogenic O6-alkylguanine (O6-alkG) lesions in DNA by a highly conserved reaction involving the stoichiometric transfer of the alkyl group to the active centre cysteine residue of the ATase protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9366274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Although the human O6-alkylguanine-DNA alkyltransferase (AGT) is very sensitive to inactivation by O6-benzylguanine (BG) or 2,4-diamino-6-benzyloxy-5-nitrosopyrimidine (5-nitroso-BP), the equivalent protein formed by the carboxyl terminal domain of the product of the Escherichia coli ada gene (Ada-C) is unaffected by these inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7634390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "A mutant of Bacillus subtilis defective in the constitutive activity of O6-alkylguanine-DNA alkyltransferase was isolated from a strain (ada-1) deficient in the adaptive response to DNA alkylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2105461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Mutations in the Ada O6-alkylguanine-DNA alkyltransferase conferring sensitivity to inactivation by O6-benzylguanine and 2,4-diamino-6-benzyloxy-5-nitrosopyrimidine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7634390", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "The protein O 6-alkylguanine-DNA alkyltransferase(alkyltransferase) is involved in the repair of O 6-alkylguanine and O 4-alkylthymine in DNA and plays an important role in most organisms in attenuating the cytotoxic and mutagenic effects of certain classes of alkylating agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10101186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "O6-Alkylguanine-DNA alkyltransferase (EC 2.1.1.63) repairs O6-alkylguanine lesions in DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7695814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Spontaneous mutagenesis in O6-alkylguanine-DNA alkyltransferase-proficient and -deficient (ada ogt mutants) Escherichia coli was studied in two ways: in bacteria growing in nonselective liquid medium and in bacteria resting on selective agar plates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9717173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "The protein O 6-alkylguanine-DNA alkyltransferase(alkyltransferase) is involved in the repair of O 6-alkylguanine and O 4-alkylthymine in DNA and plays an important role in most organisms in attenuating the cytotoxic and mutagenic effects of certain classes of alkylating agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10101186", "endSection": "abstract" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1609, "text": "In summary, this paper presents for the first time evidence that DNA repair by O6-alkylguanine-DNA alkyltransferases plays a major role in removing lesions responsible for GC-->AT transitions induced by CCNU, influencing their ultimate distribution with respect to sequence context.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8519412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Forward mutations induced by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the lacl gene of Escherichia coli were recovered from bacteria proficient (Ogt+ Ada+) and deficient (Ogt- Ada-) in O6-alkylguanine-DNA alkyltransferase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8519412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Repair of O6-benzylguanine by the Escherichia coli Ada and Ogt and the human O6-alkylguanine-DNA alkyltransferases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9079656", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "O6-Alkylguanine DNA-alkyltransferase (ATase) repairs toxic, mutagenic and carcinogenic O6-alkylguanine (O6-alkG) lesions in DNA by a highly conserved reaction involving the stoichiometric transfer of the alkyl group to the active centre cysteine residue of the ATase protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9366274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "O6-Alkylguanine-DNA alkyltransferase (EC 2.1.1.63) repairs O6-alkylguanine lesions in DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7695814", "endSection": "abstract" } ] }, { "body": "List the neurotransmitters that are metabolized by MAOA.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19214141", "http://www.ncbi.nlm.nih.gov/pubmed/24652311", "http://www.ncbi.nlm.nih.gov/pubmed/19368859", "http://www.ncbi.nlm.nih.gov/pubmed/23761378", "http://www.ncbi.nlm.nih.gov/pubmed/24510409", "http://www.ncbi.nlm.nih.gov/pubmed/25733484", "http://www.ncbi.nlm.nih.gov/pubmed/19456107", "http://www.ncbi.nlm.nih.gov/pubmed/20485326", "http://www.ncbi.nlm.nih.gov/pubmed/20204405", "http://www.ncbi.nlm.nih.gov/pubmed/24865426", "http://www.ncbi.nlm.nih.gov/pubmed/18227761", "http://www.ncbi.nlm.nih.gov/pubmed/21554924" ], "ideal_answer": [ "The monoamine oxidase-A (MAOA) gene plays a vital role in the metabolism of neurotransmitters, e.g, serotonin, norepinephrine, and dopamine." ], "exact_answer": [ [ "serotonin" ], [ "norepinephrine" ], [ "dopamine" ] ], "concepts": [ "http://www.uniprot.org/uniprot/AOFA_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018377", "http://www.uniprot.org/uniprot/AOFA_CANFA" ], "type": "list", "id": "56cf4b623975bb303a00000a", "snippets": [ { "offsetInBeginSection": 297, "offsetInEndSection": 344, "text": " MAOA metabolizes monoamine neurotransmitters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25733484", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 168, "text": "Monoamine oxidase A (MAOA) modulates metabolism of serotonin and dopamine metabolism, neurotransmitters involved in regulation of appetite and food intake. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23761378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Monoamine oxidase A (MAOA) catalyzes monoamine neurotransmitters including dopamine, 5-hydroxytryptamine (5-HT, serotonin), and norepinephrine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510409", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 505, "text": "These traits are controlled by neurotransmitters like dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of amines, has been reported to be associated with aggression, impulsivity, depression, and mood changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24652311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Monoamine Oxidase A (MAOA) is a critical enzyme in the catabolism of monoaminergic neurotransmitters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Monoamine oxidases (MAO-A and MAO-B) have a key role in the degradation of amine neurotransmitters, such as dopamine, norepinephrine and serotonin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20485326", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 218, "text": "Inhibitors of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine, are commonly used to treat neurological conditions including depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20204405", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 269, "text": " Monoamine oxidase A (MAOA) is one of the major enzymes responsible for the degradation of neurotransmitters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19368859", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Monoamine oxidase membrane enzymes are responsible for the catalytic breakdown of extra- and intracellular neurotransmitters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19456107", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 149, "text": " Monoamine oxidase-A (MAO-A) is a key mitochondrial enzyme that metabolizes biogenic amine neurotransmitters such as dopamine and serotonin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214141", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 153, "text": "The monoamine oxidase-A (MAOA) gene plays a vital role in the metabolism of neurotransmitters, e.g, serotonin, norepinephrine, and dopamine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18227761", "endSection": "abstract" } ] }, { "body": "What is the effect of enamel matrix derivative on pulp regeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12640753", "http://www.ncbi.nlm.nih.gov/pubmed/24246686", "http://www.ncbi.nlm.nih.gov/pubmed/21166828", "http://www.ncbi.nlm.nih.gov/pubmed/24279667", "http://www.ncbi.nlm.nih.gov/pubmed/23880267" ], "ideal_answer": [ "EMD increased the osteogenic potential of hDPCs. The expression levels of osteogenesis-related genes, such as ALP, DSPP, BMP, and OPN were also upregulated. In addition, the expression levels of odontogenesis-related transcription factors Osterix and Runx2 were upregulated. Proliferated pulp tissue partly filled the space initially occupied by EMDgel and isolated masses within the proliferated pulp tissue." ], "exact_answer": [ "increase of the osteogenic potential of hDPCs" ], "type": "factoid", "id": "55450521bf90a13052000001", "snippets": [ { "offsetInBeginSection": 569, "offsetInEndSection": 1018, "text": "Among the human studies, two studies reported that EMD is a more efficient DPC procedure compared with calcium hydroxide (Ca(OH)2 ). One study reported Ca(OH)2 to be more efficient for DPC than EMD. One study reported no difference in the efficacies between EMD and Ca(OH)2 for DPC. All animal studies reported EMD to be more effective in reparative dentine formation in comparison with Ca(OH)2 . EMD can provide favourable results in DPC procedures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24279667", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 892, "text": "EMD increased the osteogenic potential of hDPCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246686", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1189, "text": " the expression levels of osteogenesis-related genes, such as ALP, DSPP, BMP, and OPN were also upregulated. In addition, the expression levels of odontogenesis-related transcription factors Osterix and Runx2 were upregulated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246686", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1424, "text": "EMD could enhance the mineralization of hDPSCs upregulated the expression of markers for odontoblast/osteoblast-like cells. Further studies are required to determine if EMD can improve pulp tissue repair and regeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246686", "endSection": "abstract" }, { "offsetInBeginSection": 1997, "offsetInEndSection": 2200, "text": "In both the scaffold groups, dentin sialophosphoprotein, dentin matrix protein-1, and osteopontin messenger RNA was up-regulated significantly in EMD-treated hDPCs when compared with the nontreated cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880267", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1178, "text": "Proliferated pulp tissue partly filled the space initially occupied by EMDgel and DSP-stained hard tissue was observed alongside exposed dentine surfaces as well as in isolated masses within the proliferated pulp tissue, although the new hard tissue did not cover the pulp exposure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21166828", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 904, "text": "In the EMD-treated teeth, large amounts of newly formed dentin-like hard tissue with associated formative cells outlined the pulpal wound separating the cavity area from the remaining pulp tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12640753", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1304, "text": "Inflammatory cells were present in the wound area but not subjacent to the newly formed hard tissue. Morphometric analysis showed that the amount of hard tissue formed in EMD-treated teeth was more than twice that of the calcium-hydroxide-treated control teeth (p < 0.001), suggesting that EMD is capable of promoting reparative processes in the wounded pulp more strongly than is calcium hydroxide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12640753", "endSection": "abstract" } ] }, { "body": "Is depression associated with poor prognosis of brain tumor patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16304988", "http://www.ncbi.nlm.nih.gov/pubmed/15072475", "http://www.ncbi.nlm.nih.gov/pubmed/15918939", "http://www.ncbi.nlm.nih.gov/pubmed/16960653" ], "ideal_answer": [ "Yes. In brain tumor patients depression is associated with shorter survival and worse functional outcomes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016019", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017063", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.disease-ontology.org/api/metadata/DOID:1319", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932" ], "type": "yesno", "id": "514cc8dcd24251bc05000066", "snippets": [ { "offsetInBeginSection": 583, "offsetInEndSection": 819, "text": "Before surgery 27 patients (35%) had BDI scores indicating the presence of depression. These scores were significantly higher in patients with a history of depression (p = 0.017) and in those with a lower functional outcome (p = 0.015).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16304988", "endSection": "sections.0" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1128, "text": "A lower functional status (KPS score < or = 70) in patients was significantly associated with high depression scores at the 3-month (p = 0.000) and 1-year (p = 0.005) assessments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16304988", "endSection": "sections.0" }, { "offsetInBeginSection": 782, "offsetInEndSection": 964, "text": "At all follow-ups, depressed low-grade glioma patients had a significantly shorter survival time, 3.3-5.8 years, compared to non-depressed low-grade glioma patients, 10.0-11.7 years.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16960653", "endSection": "sections.0" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1223, "text": "The results suggest that depression and decreased QOL among low-grade glioma patients is related to shorter survival at long-term follow-up.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16960653", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 143, "text": "The adverse impact of depression in relation to survival among cancer patients is currently a subject of great interest in research.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15918939", "endSection": "sections.0" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1388, "text": "In the subgroup of patients with low-grade gliomas, depressive patients had a significantly shorter survival time compared with nondepressive subjects (P = 0.031, Kaplan-Meier survival analysis).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15918939", "endSection": "sections.0" }, { "offsetInBeginSection": 1731, "offsetInEndSection": 1848, "text": "Preoperative depression seemed to be a significant prognostic factor for worse survival in low-grade glioma patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15918939", "endSection": "sections.0" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1244, "text": "Major depressive disorder was marginally associated with outcomes, while surgical interventions and radiotherapy did not show strong associations with test performances.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15072475", "endSection": "sections.0" } ] }, { "body": "Super-SILAC is a method used in quantitative proteomics. What is the super-SILAC mix?\n(SILAC: Stable Isotopic labelling by aminoacids in cell culture)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21293456", "http://www.ncbi.nlm.nih.gov/pubmed/20364148", "http://www.ncbi.nlm.nih.gov/pubmed/22278370", "http://www.ncbi.nlm.nih.gov/pubmed/20431548", "http://www.ncbi.nlm.nih.gov/pubmed/23090970", "http://www.ncbi.nlm.nih.gov/pubmed/22442255", "http://www.ncbi.nlm.nih.gov/pubmed/22623409" ], "ideal_answer": [ "The Super-SILAC mix consists of the combination of multiple SILAC-labeled cell lines." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007553", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ], "type": "summary", "id": "51430930d24251bc0500000b", "snippets": [ { "offsetInBeginSection": 1289, "offsetInEndSection": 1371, "text": ", a mixture of five SILAC-labeled cell lines that accurately represents the tissue", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21293456", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "We describe a method to accurately quantify human tumor proteomes by combining a mixture of five stable-isotope labeling by amino acids in cell culture (SILAC)-labeled cell lines with human carcinoma tissue. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20364148", "endSection": "sections.0" } ] }, { "body": "What is an acceptable sequence coverage(depth) required for human whole-exome sequencing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22038007", "http://www.ncbi.nlm.nih.gov/pubmed/21499249", "http://www.ncbi.nlm.nih.gov/pubmed/23160641", "http://www.ncbi.nlm.nih.gov/pubmed/23647072", "http://www.ncbi.nlm.nih.gov/pubmed/24290377", "http://www.ncbi.nlm.nih.gov/pubmed/23450047", "http://www.ncbi.nlm.nih.gov/pubmed/23272691", "http://www.ncbi.nlm.nih.gov/pubmed/22952768", "http://www.ncbi.nlm.nih.gov/pubmed/22156295", "http://www.ncbi.nlm.nih.gov/pubmed/23015295", "http://www.ncbi.nlm.nih.gov/pubmed/21654732", "http://www.ncbi.nlm.nih.gov/pubmed/21943378", "http://www.ncbi.nlm.nih.gov/pubmed/23357921", "http://www.ncbi.nlm.nih.gov/pubmed/23728943", "http://www.ncbi.nlm.nih.gov/pubmed/24065236", "http://www.ncbi.nlm.nih.gov/pubmed/22654895", "http://www.ncbi.nlm.nih.gov/pubmed/23349227", "http://www.ncbi.nlm.nih.gov/pubmed/23940558" ], "ideal_answer": [ "A medium depth may be considered as 8x while the most common values vary between 30x and 60x. Values more than 75x or even up to 125x may be considered for the investigation of rare disease variants." ], "exact_answer": [ "30x-60x" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059014", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059472" ], "type": "factoid", "id": "533c390bc45e13371400000b", "snippets": [ { "offsetInBeginSection": 543, "offsetInEndSection": 708, "text": "A total of 5.97 Gb clean data were generated for the two samples, achieving a mean depth of coverage of 31.96 and 32.88 for the AAA and normal samples, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065236", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 970, "text": "The 1.7 Mb targeted regions were sequenced with a coverage ranged from 32\u00d7 to 45\u00d7 for the 28 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940558", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 425, "text": "We performed whole-exome sequencing on 87 HCCs and matched normal adjacent tissues to an average coverage of 59\u00d7", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728943", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1192, "text": "We performed WES (mean coverage approximately 40\u00d7) on 10 trios comprised of unaffected parents and a child with sporadic epilepsy characterized by difficult-to-control seizures and some combination of developmental delay, epileptic encephalopathy, autistic features, cognitive impairment, or motor deficits. Sequence processing and variant calling were performed using standard bioinformatics tools.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23647072", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 712, "text": "Whole-exome sequencing achieved a high degree of coverage such that approximately 97% of targeted bases were represented by more than 10 base reads;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450047", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 628, "text": "AbCD is a user-friendly interface providing pre-estimated effective sample sizes, specific to each minor allele frequency category, for designs with arbitrary coverage (0.5-30\u00d7) and sample size (20-10 000), and for four major ethnic groups (Europeans, Africans, Asians and African Americans). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357921", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1031, "text": "Next generation sequencing with mean coverage of 50\u00d7 using the Illumina Hi Seq and whole exome capture processing was performed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349227", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1571, "text": "mtDNA genome coverage varied depending on the mtDNA:nuclear blend ratio, where a 1:100 ratio provided optimal dual-genome coverage with 10X coverage for over 97.5% of all targeted nuclear regions and 1,000X coverage for 99.8% of the mtDNA genome. mtDNA mutations were reliably detected to at least an 8% heteroplasmy level, as discriminated both from sequencing errors and potential contamination from nuclear mtDNA transcripts (Numts).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272691", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 974, "text": "Each sample was sequenced to a mean depth of coverage of greater than 120\u00d7", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015295", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1019, "text": "Long-PCR targeting was more efficient with up to 94% of USH gene regions displaying an overall coverage higher than 25\u00d7, whereas whole exome sequencing yielded a similar coverage for only 50% of those regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952768", "endSection": "abstract" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1448, "text": "WES reads covered 91% of the target capture region (of size 37.2\u2009MB) with an average coverage of 65\u00d7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22654895", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 296, "text": "We captured 162,073 exons of 16,954 genes and sequenced the targeted regions to a mean coverage of 56-fold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22156295", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 359, "text": "The specificity of exome enrichment was approximately 80% with 95.6% even coverage of the 34 Mb target region at an average sequencing depth of 33-fold", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038007", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 710, "text": "We generated over 4.7 GB of mappable sequence to a 125X read coverage per sample.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21943378", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 543, "text": "By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36\u00d7 coverage) and matched lymphocytes (>28\u00d7 coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21499249", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 975, "text": "Whole-exome sequencing at a higher sequence depth (>76\u00d7 coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21499249", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 354, "text": "We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index\u00a0> 27.5\u00a0kg/m(2) and hypertension) and 1,000 healthy controls to an average depth of 56\u00d7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24290377", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 456, "text": "We performed medium-depth (8\u00d7) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5\u00a0kg/m(2) and hypertension and in 1,000 controls (stage 1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23160641", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1031, "text": "Next generation sequencing with mean coverage of 50\ufffd using the Illumina Hi Seq and whole exome capture processing was performed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349227", "endSection": "abstract" } ] }, { "body": "To what extent does HPV vaccination reduce the risk for cervical cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18482556", "http://www.ncbi.nlm.nih.gov/pubmed/19901442", "http://www.ncbi.nlm.nih.gov/pubmed/19901441", "http://www.ncbi.nlm.nih.gov/pubmed/18055075", "http://www.ncbi.nlm.nih.gov/pubmed/21245659", "http://www.ncbi.nlm.nih.gov/pubmed/17318575", "http://www.ncbi.nlm.nih.gov/pubmed/20593935", "http://www.ncbi.nlm.nih.gov/pubmed/18716299", "http://www.ncbi.nlm.nih.gov/pubmed/23016781", "http://www.ncbi.nlm.nih.gov/pubmed/19200838", "http://www.ncbi.nlm.nih.gov/pubmed/21289891" ], "ideal_answer": [ "The most effective strategy therein was vaccination of 12-year-olds, plus a temporary 12-24-year-old catch-up program covering both sexes; whereby HPV 6/11/16/18-related cervical cancer, high-grade cervical precancer, and genital wart incidence was reduced by 84-98% during year 50 following vaccine introduction. Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%" ], "exact_answer": [ "Cervical precancer and similar neoplasias were reduced by 84-100%" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014611", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053918", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014612", "http://www.disease-ontology.org/api/metadata/DOID:4362" ], "type": "factoid", "id": "531a3a58b166e2b806000037", "snippets": [ { "offsetInBeginSection": 891, "offsetInEndSection": 1126, "text": "The success of HPV vaccination as a major public health prevention opportunity, however, will entirely depend on efficient infrastructures to deliver the vaccines and on the acceptance by individuals, parents and health care providers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17318575", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 811, "text": "The most effective strategy therein was vaccination of 12-year-olds, plus a temporary 12-24-year-old catch-up program covering both sexes; whereby HPV 6/11/16/18-related cervical cancer, high-grade cervical precancer, and genital wart incidence was reduced by 84-98% during year 50 following vaccine introduction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18055075", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 129, "text": "the introduction of cervical screening programs, the incidence and mortality of cervical cancer has been drastically reduced", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18482556", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1088, "text": "On the assumption that the vaccine provided lifelong immunity, the cost-effectiveness ratio of vaccination of 12-year-old girls was $43,600 per quality-adjusted life-year (QALY) gained, as compared with the current screening practice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18716299", "endSection": "abstract" }, { "offsetInBeginSection": 1573, "offsetInEndSection": 1730, "text": "Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21289891", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1209, "text": "Life expectancy gained from vaccination is 13.04 years and average Quality Adjusted Life Years saved (QALYs) is 24.4 in vaccinated vs 6.29 in unvaccinated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20593935", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 862, "text": "Organized vaccination programs against HPV have the potential to prevent about 70% of cervical cancers and the vast majority of the other HPV-related conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21245659", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 378, "text": "However, existing data strongly suggests that as many as 440,000 cervical cancer cases and 220,000 deaths due to this malignancy will be prevented with the establishment of an effective worldwide HPV immunization program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23016781", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 415, "text": "Prophylactic HPV vaccination against HPV 16 and 18 has been shown to be highly effective in preventing HPV related malignancy in clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19200838", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1418, "text": "Nevertheless women up to 45 years of age have been shown to exhibit strong immune responses to the bivalent HPV vaccine which might be expected to reduce the risk of HPV re-infection and address the second peak of HPV related malignancy in later life, evident over 45 years of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19200838", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1148, "text": "Reduced costs, simple vaccine regimes and strengthening vaccine delivery platforms for adolescents should eventually facilitate HPV vaccine introduction in developing countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901441", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1239, "text": "Besides cost, there are several socio-cultural and ethical issues involved with the implementation of already developed vaccines including the acceptability of HPV vaccination by preadolescent girls and their parents in India.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901442", "endSection": "abstract" } ] }, { "body": "Have germline variants been associated to colorectal cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22020387", "http://www.ncbi.nlm.nih.gov/pubmed/21351276", "http://www.ncbi.nlm.nih.gov/pubmed/22431159", "http://www.ncbi.nlm.nih.gov/pubmed/17524638", "http://www.ncbi.nlm.nih.gov/pubmed/18091433", "http://www.ncbi.nlm.nih.gov/pubmed/17604324", "http://www.ncbi.nlm.nih.gov/pubmed/21918173", "http://www.ncbi.nlm.nih.gov/pubmed/21791631", "http://www.ncbi.nlm.nih.gov/pubmed/23263490" ], "ideal_answer": [ "Yes. Whole-genome sequencing (WGS) applied to medical research has revealed how germline variants and mutations may be associated with colorectal cancer. It is likely that this level of knowledge can be translated into predictions of predisposition." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059014" ], "type": "yesno", "id": "5161cfa3298dcd4e5100003d", "snippets": [ { "offsetInBeginSection": 288, "offsetInEndSection": 766, "text": "Overall, we identified aberrant transcripts in 8% of the patients (familial cases 30%; early-onset manifestation 21%). In eight of them, two different out-of-frame pseudoexons were found consisting of a 167-bp insertion from intron 4 in five families with a shared founder haplotype and a 83-bp insertion from intron 10 in three patients. The pseudoexon formation was caused by three different heterozygous germline mutations, which are supposed to activate cryptic splice sites", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431159", "endSection": "sections.0" }, { "offsetInBeginSection": 270, "offsetInEndSection": 717, "text": "We apply OS-Seq to resequence the exons of either 10 or 344 cancer genes from human DNA samples. In our assessment of capture performance, >87% of the captured sequence originated from the intended target region with sequencing coverage falling within a tenfold range for a majority of all targets. Single nucleotide variants (SNVs) called from OS-Seq data agreed with >95% of variants obtained from whole-genome sequencing of the same individual.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020387", "endSection": "sections.0" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1545, "text": "The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35-0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33-0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12-0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71-16.63, P < 0.001).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21918173", "endSection": "sections.0" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1677, "text": "In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21791631", "endSection": "sections.0" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1354, "text": "We identified 22 nonsynonymous somatic mutations of which the majority was of missense type. In germline, three novel nonsynonymous variants were identified in the following genes: CSMD3, EPHB6 and C10orf137, and none of the variants were present in 890 population-matched healthy controls. It is possible that the identified germline variants modulate predisposition to CRC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21351276", "endSection": "sections.0" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1246, "text": "One patient proved to carry an APC whole-gene deletion; 4 of 25 (16%) patients showed biallelic and 3 of 25 (12%) monoallelic MUTYH mutations. In the three heterozygous subjects no pathogenetic variants were found in OGG1, MTH1, APE1, MSH2, and MSH6 genes. Frequency assessment of MUTYH mutations in healthy subjects showed that only Y165C and G382D reach a subpolymorphic frequency.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18091433", "endSection": "sections.0" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1355, "text": "Scrutinizing the molecular genetic results and family data of 242 index patients with pathogenic APC mutations led to the identification of 10 mosaic cases (4%). C>T transitions were observed in CGA sites in four of the 10 cases with somatic mosaicism, which is significantly more than 26 of the 232 non-mosaic cases (p = 0.02). Phenotypes of patients with somatic mosaicism ranged from an attenuated form of polyposis coli to florid polyposis with major extracolonic manifestations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17604324", "endSection": "sections.0" }, { "offsetInBeginSection": 494, "offsetInEndSection": 936, "text": "Altogether 12 previously reported changes and four novel genetic alterations, mostly in intronic sequences, were identified. The results revealed the presence of biallelic germline MYH mutations in two patients. These patients were compound heterozygotes for two of the most common germline mutations c.494 A>G (p.Y165C); c.1,145 G>A (p.G382D). These variants are established to be associated with adenomatous polyposis and colorectal cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17524638", "endSection": "sections.0" } ] }, { "body": "Can Alzheimer's disease related miRNAs be detected in patients' blood?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23030236", "http://www.ncbi.nlm.nih.gov/pubmed/23054683", "http://www.ncbi.nlm.nih.gov/pubmed/21548758", "http://www.ncbi.nlm.nih.gov/pubmed/22155483", "http://www.ncbi.nlm.nih.gov/pubmed/23435408", "http://www.ncbi.nlm.nih.gov/pubmed/23528227", "http://www.ncbi.nlm.nih.gov/pubmed/21709374", "http://www.ncbi.nlm.nih.gov/pubmed/19936094" ], "triples": [ { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10477709", "o": "Blood" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10339464", "o": "http://purl.uniprot.org/pubmed/10339464" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10572112", "o": "Blood" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/11110714", "o": "Blood" } ], "ideal_answer": [ "Yes. It has been demonstrated that blood miRNAs could be useful as biomarkers in Alzheimer's disease." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001773", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001798", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016229", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023582", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "yesno", "id": "5156beb4d24251bc05000089", "snippets": [ { "offsetInBeginSection": 469, "offsetInEndSection": 783, "text": "miRNAs are aberrantly expressed in AD, and these have been implicated in the regulation of amyloid-\u03b2 (A\u03b2) peptide, tau, inflammation, cell death, and other aspects which are the main pathomechanisms of AD. In addition, regulation of miRNAs varies in blood, and cerebral spinal fluid may indicate alterations in AD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23054683", "endSection": "sections.0" }, { "offsetInBeginSection": 251, "offsetInEndSection": 407, "text": "miRNA microarray analysis was carried out on blood of rats at 1 week and 2 months after injection. RESULTS: Many up- and downregulated miRNAs were detected.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030236", "endSection": "sections.0" }, { "offsetInBeginSection": 536, "offsetInEndSection": 712, "text": "Blood miRNAs could be useful as biomarkers for exposure to nanoparticles. miR-298 regulates \u03b2-amyloid (A\u03b2) precursor protein-converting enzyme-1 (BACE1) in Alzheimer's disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030236", "endSection": "sections.0" }, { "offsetInBeginSection": 115, "offsetInEndSection": 484, "text": " We previously studied microRNAs (miRNAs) in AD autopsy brain samples and reported a connection between miR-137, -181c, -9, -29a/b and AD, through the regulation of ceramides. In this study, the potential role of these miRNAs as diagnostic markers for AD was investigated. We identified that these miRNAs were down-regulated in the blood serum of probable AD patients. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155483", "endSection": "sections.0" }, { "offsetInBeginSection": 173, "offsetInEndSection": 399, "text": "287 with Alzheimer disease (AD) as compared with 344 age- and gender-matched controls. In addition, we evaluated expression levels of hnRNP-A1 and its regulatory microRNA (miR)-590-3p in blood cells from patients and controls.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548758", "endSection": "sections.0" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1470, "text": "Decreased relative expression levels of hsa-miR-590-3p was observed in patients with AD versus controls (0.685\u2009\u00b1\u20090.080 versus 0.931\u2009\u00b1\u20090.111, p\u2009=\u20090.079), and correlated negatively with hnRNP-A1 mRNA levels (r\u2009=\u2009-0.615, p\u2009=\u20090.0237).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548758", "endSection": "sections.0" }, { "offsetInBeginSection": 622, "offsetInEndSection": 809, "text": "expression analysis of Sp1 and its regulatory microRNAs (hsa-miR-29b and hsa-miR-375) has been performed in peripheral blood mononuclear cells (PBMCs), together with Sp1 protein analysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435408", "endSection": "sections.0" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1427, "text": "Significantly decreased relative expression levels of hsa-miR-29b, but not of hsa-miR-375, were observed in AD patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435408", "endSection": "sections.0" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1684, "text": "Sp1 and its regulatory hsa-miR-29b are deregulated in AD patients, possibly leading to aberrant production of downstream target genes involved in the pathogenesis. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435408", "endSection": "sections.0" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1282, "text": "We previously observed that miR-137, -181c, -9, and 29a/b post-transcriptionally regulate SPT levels, and the corresponding miRNA levels in the blood sera are potential diagnostic biomarkers for AD. Here, we observe a negative correlation between cortical A\u03b242 and sera A\u03b242, and a positive correlation between cortical miRNA levels and sera miRNA levels suggesting their potential as noninvasive diagnostic biomarkers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23528227", "endSection": "sections.0" } ] }, { "body": "Which is the clinical meaning of the presence of delayed enhancement in patients with hypertrophic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18552138", "http://www.ncbi.nlm.nih.gov/pubmed/21498307", "http://www.ncbi.nlm.nih.gov/pubmed/20102955", "http://www.ncbi.nlm.nih.gov/pubmed/18387438", "http://www.ncbi.nlm.nih.gov/pubmed/19477402", "http://www.ncbi.nlm.nih.gov/pubmed/23097128", "http://www.ncbi.nlm.nih.gov/pubmed/19808288", "http://www.ncbi.nlm.nih.gov/pubmed/22641976" ], "ideal_answer": [ "Occurrence of myocardial fibrosis in hypertrophic cardiomyopathy is associated with left atrial and ventricular dysfunction as well as with the severity of heart failure symptoms and arrhythmic risk factors." ], "exact_answer": [ "In patients with hypertrophic cardiomyopathy delayed enhancement is associated with heart failure symptoms and left ventricular systolic dysfunction and arrhythmic risk" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11984", "http://www.disease-ontology.org/api/metadata/DOID:11986", "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009682", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024741", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010361" ], "type": "factoid", "id": "5339edd6d6d3ac6a34000061", "snippets": [ { "offsetInBeginSection": 1464, "offsetInEndSection": 1664, "text": "The extent of regional myocardial fibrosis is associated with regional myocardial function independently of morphological changes of the myocardium, and the correlation extended to global LV function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23097128", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1785, "text": "Occurrence of myocardial fibrosis in hypertrophic cardiomyopathy is associated with left atrial and ventricular dysfunction as well as with the severity of heart failure symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22641976", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1595, "text": "Patients with symptomatic apical HCMshowed myocardial hyperenhancement involving the subendocardial layer, which might be related to regional systolic dysfunction, serious clinical symptoms, and ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498307", "endSection": "abstract" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1269, "text": "In conclusion, late gadolinium enhancement was associated with nonsustained ventricular tachycardia, arrhythmic risk factors, and worse New York Heart Association class.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20102955", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 798, "text": "The presence of DE was related to occurrence of heart failure symptoms (P=0.05) and left ventricular systolic dysfunction (P=0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808288", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1183, "text": "DE (7%+/-7% of left ventricle) was present in 54 patients who were asymptomatic (and with normal ejection fraction). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808288", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1330, "text": "In HCM, the DE was associated with higher NYHA classes and prevalence of VT, impaired global LV function and asymmetrical hypertrophy, and conduction disturbance, abnormal Q waves, and giant negative T waves.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19477402", "endSection": "abstract" }, { "offsetInBeginSection": 1482, "offsetInEndSection": 1951, "text": " In myocardial segments exhibiting DCE, hMBF is reduced. DCE extent is inversely correlated and hMBF directly correlated with systolic thickening. In segments without DCE but contiguous to DCE areas, hMBF is significantly lower than in those remote from DCE and is similar to the value obtained in nontransmural DCE segments. These results suggest that increasing degrees of coronary microvascular dysfunction might play a causative role for myocardial fibrosis in HCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18552138", "endSection": "abstract" }, { "offsetInBeginSection": 1334, "offsetInEndSection": 1683, "text": "In this large HCM cohort with no or only mild symptoms, myocardial fibrosis detected by CMR was associated with greater likelihood and increased frequency of ventricular tachyarrhythmias (including NSVT) on ambulatory Holter ECG. Therefore, contrast-enhanced CMR identifies HCM patients with increased susceptibility to ventricular tachyarrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18387438", "endSection": "abstract" } ] }, { "body": "What disease is mirtazapine predominantly used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19034656", "http://www.ncbi.nlm.nih.gov/pubmed/19412502", "http://www.ncbi.nlm.nih.gov/pubmed/21810375", "http://www.ncbi.nlm.nih.gov/pubmed/21071407", "http://www.ncbi.nlm.nih.gov/pubmed/17440145", "http://www.ncbi.nlm.nih.gov/pubmed/15052512", "http://www.ncbi.nlm.nih.gov/pubmed/16280409", "http://www.ncbi.nlm.nih.gov/pubmed/21810886", "http://www.ncbi.nlm.nih.gov/pubmed/12908614", "http://www.ncbi.nlm.nih.gov/pubmed/15520364", "http://www.ncbi.nlm.nih.gov/pubmed/19016570", "http://www.ncbi.nlm.nih.gov/pubmed/23018612" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/852", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00370" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A11577558", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0600233", "o": "mirtazapine" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A18168147", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17928971", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11898470", "o": "Mirtazapine" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17977028", "o": "mirtazapine" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11575491", "o": "mirtazapine" } ], "ideal_answer": [ "Mirtazapine is predominantly used in the treatment of major depression." ], "exact_answer": [ "major depression" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007202", "http://www.biosemantics.org/jochem#4134182", "http://www.biosemantics.org/jochem#4191931" ], "type": "factoid", "id": "5156be17d24251bc05000086", "snippets": [ { "offsetInBeginSection": 1475, "offsetInEndSection": 1565, "text": "mirtazapine will make it the first-choice drug in depressive patients with gastric ulcers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19034656", "endSection": "sections.0" }, { "offsetInBeginSection": 1695, "offsetInEndSection": 2460, "text": "If antidepressants are used to treat insomnia, sedating ones should be preferred over activating agents such as serotonin reuptake inhibitors. In general, drugs lacking strong cholinergic activity should be preferred. Drugs blocking serotonin 5-HT2A or 5-HT2C receptors should be preferred over those whose sedative property is caused by histamine receptor blockade only. The dose should be as low as possible (e.g. as an initial dose: doxepin 25 mg, mirtazapine 15 mg, trazodone 50 mg, trimipramine 25 mg). Regarding the lack of substantial data allowing for evidence-based recommendations, we are facing a clear need for well designed, long-term, comparative studies to further define the role of antidepressants versus other agents in the management of insomnia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19016570", "endSection": "sections.0" }, { "offsetInBeginSection": 770, "offsetInEndSection": 970, "text": "second-generation antidepressants (selective serotonin reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine) in participants younger than 19 years with MDD, OCD, or non-OCD anxiety disorders.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17440145", "endSection": "sections.0" }, { "offsetInBeginSection": 731, "offsetInEndSection": 897, "text": "patients 65 years or older with major depression. METHODS: Antidepressant therapy with 15 to 45 mg/d of mirtazapine (n = 124) or 20 to 40 mg/d of paroxetine (n = 122)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520364", "endSection": "sections.0" }, { "offsetInBeginSection": 521, "offsetInEndSection": 710, "text": "A case report involving linezolid with citalopram and mirtazepine in the precipitation of serotonin syndrome in a critically ill bone marrow transplant patient is described in this article.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16280409", "endSection": "sections.0" }, { "offsetInBeginSection": 2266, "offsetInEndSection": 2885, "text": "other antidepressants was associated with the highest HRs for all-cause mortality (1.66, 95% CI 1.56 to 1.77), attempted suicide/self-harm (5.16, 95% CI 3.90 to 6.83), stroke/TIA (1.37, 95% CI 1.22 to 1.55), fracture (1.63, 95% CI 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 1.60 to 3.15) compared with when antidepressants were not being used. TCAs did not have the highest HR for any of the outcomes. There were also significantly different associations between the individual drugs for seven outcomes, with trazodone, mirtazapine and venlafaxine associated with the highest rates for several of these outcomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21810375", "endSection": "sections.0" }, { "offsetInBeginSection": 2237, "offsetInEndSection": 2569, "text": "But when trazodone, amitriptyline or mirtazapine were used to treat depression, respectively, 92.3, 55.5 and 44.5 % of prescribed dosages were below the MED. In the indication of insomnia, most of the time, trazodone (90.5 %) or mirtazapine (5.4 %) were used, and in lower dosages than those required for depression treatment (100 kb) hypomethylation. These hypomethylated domains covered nearly half of the genome and coincided with late replication and attachment to the nuclear lamina in human cell lines", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120008", "endSection": "sections.0" }, { "offsetInBeginSection": 791, "offsetInEndSection": 845, "text": "the confluence of hypermethylation and hypomethylation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120008", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19639607", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "CpG island hypermethylation and genomic DNA hypomethylation are found not only in gastric cancers but also in associated premalignant lesions", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19639607", "endSection": "sections.0" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1250, "text": "Methylation of repetitive DNA elements in gastric lesions generally decreased with progression of the gastric lesion along the multistep carcinogenesi", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19639607", "endSection": "sections.0" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1720, "text": "our findings suggest that CpG island hypermethylation and repetitive DNA hypomethylation are enhanced with progression of the gastric lesion", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19639607", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "DNA hypomethylation arises later in prostate cancer progression than CpG island hypermethylation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974140", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Hypomethylation of CpG dinucleotides in genomic DNA was one of the first somatic epigenetic alterations discovered in human cancers. DNA hypomethylation is postulated to occur very early in almost all human cancers, perhaps facilitating genetic instability and cancer initiation and progression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974140", "endSection": "sections.0" }, { "offsetInBeginSection": 406, "offsetInEndSection": 699, "text": "Contrary to the prevailing view that global DNA hypomethylation changes occur extremely early in all human cancers, we show that reductions in (5me)C content in the genome occur very late in prostate cancer progression, appearing at a significant extent only at the stage of metastatic disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974140", "endSection": "sections.0" }, { "offsetInBeginSection": 1557, "offsetInEndSection": 1796, "text": "These findings provide evidence that DNA hypomethylation changes occur later in prostate carcinogenesis than the CpG island hypermethylation changes and occur heterogeneously during prostate cancer progression and metastatic dissemination.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974140", "endSection": "sections.0" }, { "offsetInBeginSection": 735, "offsetInEndSection": 835, "text": "revealed a high incidence of hypermethylation only in poorly differentiated (early and late) tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18667590", "endSection": "sections.0" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1404, "text": "In contrast to gene hypermethylation, genomic DNA hypomethylation, including hypomethylation of repetitive elements and loss of genomic 5-methyldeoxycytidine, occurred in both early and late stages of prostate cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18667590", "endSection": "sections.0" }, { "offsetInBeginSection": 85, "offsetInEndSection": 178, "text": "Tumors have reduced levels of genomic DNA methylation and contain hypermethylated CpG islands", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18162535", "endSection": "sections.0" }, { "offsetInBeginSection": 1113, "offsetInEndSection": 1222, "text": "The results are consistent with a specific defect in methylation of repetitive DNA sequences in human cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18162535", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Both hypomethylation and hypermethylation in a 0.2-kb region of a DNA repeat in cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16317087", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Differential DNA hypermethylation and hypomethylation signatures in colorectal cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15574462", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Cancer cells are characterized by a generalized disruption of the DNA methylation pattern involving an overall decrease in the level of 5-methylcytosine together with regional hypermethylation of particular CpG islands", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15574462", "endSection": "sections.0" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1739, "text": "We conclude that DNA hypermethylation and hypomethylation are independent processes and appear to play different roles in colorectal tumor progression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15574462", "endSection": "sections.0" } ] }, { "body": "Do thyroid hormone receptors change after brain injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14761671", "http://www.ncbi.nlm.nih.gov/pubmed/24174657", "http://www.ncbi.nlm.nih.gov/pubmed/6329444" ], "ideal_answer": [ "thyroid hormone receptors increase after brain injury" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001930", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988" ], "type": "yesno", "id": "533e50fdc45e13371400000f", "snippets": [ { "offsetInBeginSection": 786, "offsetInEndSection": 984, "text": "For example, the T3 receptor alpha was predominantly expressed in stroke-tissue, indicating that regeneration of nerves in stroke tissue may be facilitated by increased T3 receptor alpha expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14761671", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1044, "text": "TR\u03b1 expression was also increased in human infants with IVH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24174657", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1595, "text": "Thus, in infants with IVH the combined elevation in deiodinase-3 and reduction in deiodinase-2 decreases TH signaling that can be worsened by an increase in unliganded TR\u03b1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24174657", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 758, "text": "A rapid increase of the total number of binding sites for T3 appeared within 30 min of ischemia and reached over 40% by 3 h. During the same 3-h period, the relative binding affinity was reduced by 25%. Upon recirculation after 30 min or 3 h of ischemia, a rapid reversal of measured T3 binding sites occurred, which progressed to 20-30% below the control value by the recirculation period of 3 h. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6329444", "endSection": "abstract" } ] }, { "body": "What is known about efficacy of the high dose intravenous ascorbate in the treatment of cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10963459", "http://www.ncbi.nlm.nih.gov/pubmed/23947403", "http://www.ncbi.nlm.nih.gov/pubmed/1749589", "http://www.ncbi.nlm.nih.gov/pubmed/11384106", "http://www.ncbi.nlm.nih.gov/pubmed/15068981", "http://www.ncbi.nlm.nih.gov/pubmed/21672627", "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "http://www.ncbi.nlm.nih.gov/pubmed/23621620", "http://www.ncbi.nlm.nih.gov/pubmed/20400857", "http://www.ncbi.nlm.nih.gov/pubmed/19731754", "http://www.ncbi.nlm.nih.gov/pubmed/24571058", "http://www.ncbi.nlm.nih.gov/pubmed/24500402", "http://www.ncbi.nlm.nih.gov/pubmed/22205155", "http://www.ncbi.nlm.nih.gov/pubmed/23381814", "http://www.ncbi.nlm.nih.gov/pubmed/24500406", "http://www.ncbi.nlm.nih.gov/pubmed/16570523", "http://www.ncbi.nlm.nih.gov/pubmed/17502128", "http://www.ncbi.nlm.nih.gov/pubmed/20171954", "http://www.ncbi.nlm.nih.gov/pubmed/18450228" ], "ideal_answer": [ "It was reported that ascorbate, given orally and intravenously at doses of up to 10\u2009g/day, was effective in the treatment of cancer. However, double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. Pharmacologic actions of ascorbate against cancer cells remain to be fully understood. It is thought that high dose ascorbate is selectively cytotoxic to cancer cell lines through the generation of extracellular hydrogen peroxide. High dose intravenous ascorbate (IVC) may be able to modulate inflammation, which in turn might improve outcomes for cancer patients. IVC may serve as a safe, adjunctive therapy in clinical cancer care" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162" ], "type": "summary", "id": "54f0985994afd6150400001a", "snippets": [ { "offsetInBeginSection": 1792, "offsetInEndSection": 1983, "text": "Evidence suggests that IVC may be able to modulate inflammation, which in turn might improve outcomes for cancer patients. IVC may serve as a safe, adjunctive therapy in clinical cancer care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23947403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "SIGNIFICANCE: Ewan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10\u2009g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621620", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 997, "text": "RECENT ADVANCES: High dose ascorbate is selectively cytotoxic to cancer cell lines through the generation of extracellular hydrogen peroxide (H2O2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621620", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1428, "text": " CRITICAL ISSUES: Neither the selective toxicity of pharmacologic ascorbate against cancer cells nor the mechanism of H2O2-mediated cytotoxicity is fully understood. Despite promising preclinical data, the question of clinical efficacy remains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23621620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23381814", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1320, "text": "CONCLUSIONS: Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23381814", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1411, "text": " IVC treatments on all aggressive stage cancer patients showed the poor response of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "endSection": "abstract" }, { "offsetInBeginSection": 1732, "offsetInEndSection": 2124, "text": "CONCLUSIONS: The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Recent studies have revealed the scientific basis for the use of intravenous (i.v.) vitamin C or ascorbic acid (ascorbate) in treating cancers, and raised the possibility of using i.v. ascorbate as a prooxidant anticancer therapy. Through the production of H2O2, pharmacologic ascorbate can induce some cancer cell death in vitro and inhibit a number of types of tumor growth in animal models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22205155", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1475, "text": "Taken together with previous studies, high-dose ascorbate has the potential to be a novel treatment option to hormone-refractory prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22205155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Two popular complementary, alternative, and integrative medicine therapies, high-dose intravenous ascorbic acid (AA) and intravenous glutathione (GSH), are often coadministered to cancer patients with unclear efficacy and drug-drug interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21672627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "Ascorbate (ascorbic acid, vitamin C) is one of the early, unorthodox treatments for cancer. The evidence upon which people base the use of ascorbate in cancer treatment falls into two categories: clinical data on dose concentration relationships, and laboratory data describing potential cell toxicity with high concentrations of ascorbate in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20400857", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 157, "text": "Recently, high dose of ascorbate in cancer treatment has been reexamined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20171954", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 746, "text": "These data suggest that ascorbic acid may have benefits for patients with mesothelioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20171954", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 877, "text": "Although, a couple of controlled clinical studies conducted at The Mayo Clinic did not support a significant benefit for terminal cancer patients after 10 grams of once-a-day oral vitamin C, other clinical trials have demonstrated that ascorbate may indeed be effective against tumors when administered intravenously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450228", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 483, "text": "Both these regressions coincided exactly in time with intravenous high-dose ascorbate administration, and it seemed reasonable to conclude that this unconventional therapy must have been responsible for his excellent responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1749589", "endSection": "abstract" }, { "offsetInBeginSection": 1928, "offsetInEndSection": 2063, "text": "In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24571058", "endSection": "abstract" }, { "offsetInBeginSection": 1878, "offsetInEndSection": 2124, "text": "In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 379, "text": "In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "endSection": "abstract" }, { "offsetInBeginSection": 1838, "offsetInEndSection": 2083, "text": "In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22963460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24571058", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1291, "text": "Because the efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18450228", "endSection": "abstract" } ] }, { "body": "Alpha-spectrin and beta-spectrin subunits form parallel or antiparallel heterodimers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21527722", "http://www.ncbi.nlm.nih.gov/pubmed/10652315", "http://www.ncbi.nlm.nih.gov/pubmed/14747656", "http://www.ncbi.nlm.nih.gov/pubmed/14761982", "http://www.ncbi.nlm.nih.gov/pubmed/21215336", "http://www.ncbi.nlm.nih.gov/pubmed/15522301", "http://www.ncbi.nlm.nih.gov/pubmed/1634521", "http://www.ncbi.nlm.nih.gov/pubmed/11502188", "http://www.ncbi.nlm.nih.gov/pubmed/9356261", "http://www.ncbi.nlm.nih.gov/pubmed/3517024", "http://www.ncbi.nlm.nih.gov/pubmed/9115173" ], "ideal_answer": [ "Alpha and beta spectrin subunits form antiparallel spectrin heterodimers by lateral association." ], "exact_answer": [ "antiparallel" ], "concepts": [ "http://www.biosemantics.org/jochem#4249968", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008091" ], "type": "factoid", "id": "5540b9800083d1bf0e000002", "snippets": [ { "offsetInBeginSection": 1185, "offsetInEndSection": 1258, "text": "\u03b1- and \u03b2-spectrin by LC-MS/MS identifies Cys in these antiparallel chains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527722", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 90, "text": "antiparallel spectrin heterodimers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14761982", "endSection": "title" }, { "offsetInBeginSection": 457, "offsetInEndSection": 565, "text": "alpha- and beta-spectrins are stable as monomeric forms but occur physiologically as alpha,beta-heterodimers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14761982", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 894, "text": "human erythroid alpha-spectrin repeats 13 and 14 (HEalpha13,14) and human erythroid beta-spectrin repeats 8 and 9 (HEbeta8,9), are located opposite each other on antiparallel spectrin dimers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14747656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Spectrins comprise \u03b1- and \u03b2-subunits made up predominantly of a series of homologous repeating units of about 106 amino acids; the \u03b1- and \u03b2-chains form antiparallel dimers by lateral association", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21215336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The spectrin heterodimer is formed by the antiparallel lateral association of an alpha and a beta subunit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10652315", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 890, "text": "Two of the less stably folded fragments, human erythroid alpha-spectrin repeats 13 and 14 (HEalpha13,14) and human erythroid beta-spectrin repeats 8 and 9 (HEbeta8,9), are located opposite each other on antiparallel spectrin dimers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14747656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Influence of lateral association on forced unfolding of antiparallel spectrin heterodimers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14761982", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The antiparallel side-to-side association of spectrin alpha and beta monomers is a two-step process which occurs in seconds even at 0 degrees C and at low concentrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1634521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The spectrin heterodimer is formed by the antiparallel lateral association of an alpha and a beta subunit, each of which comprises largely a series of homologous triple-helical motifs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10652315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Human erythrocyte spectrin is an antiparallel heterodimer comprised of a 280 kDa alpha subunit and a 246 kDa beta subunit which further associates into tetramers in the red cell membrane cytoskeleton", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11502188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The spectrin heterodimer is formed by the antiparallel lateral association of an alpha and a beta subunit, each of which comprises largely a series of homologous triple-helical motifs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10652315", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 917, "text": "The basic unit of spectrin is an antiparallel heterodimer composed of two homologous chains, beta and alpha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9356261", "endSection": "abstract" } ] }, { "body": "Is gastro esophageal reflux related to burning mouth syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8725589", "http://www.ncbi.nlm.nih.gov/pubmed/17849966", "http://www.ncbi.nlm.nih.gov/pubmed/3244997", "http://www.ncbi.nlm.nih.gov/pubmed/23201368", "http://www.ncbi.nlm.nih.gov/pubmed/10546306", "http://www.ncbi.nlm.nih.gov/pubmed/21359587", "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "http://www.ncbi.nlm.nih.gov/pubmed/12617256", "http://www.ncbi.nlm.nih.gov/pubmed/14969159", "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "http://www.ncbi.nlm.nih.gov/pubmed/18343329", "http://www.ncbi.nlm.nih.gov/pubmed/23050296", "http://www.ncbi.nlm.nih.gov/pubmed/24096230", "http://www.ncbi.nlm.nih.gov/pubmed/23589947", "http://www.ncbi.nlm.nih.gov/pubmed/8543701", "http://www.ncbi.nlm.nih.gov/pubmed/9237148", "http://www.ncbi.nlm.nih.gov/pubmed/18284539", "http://www.ncbi.nlm.nih.gov/pubmed/19938882", "http://www.ncbi.nlm.nih.gov/pubmed/23809306", "http://www.ncbi.nlm.nih.gov/pubmed/19658340", "http://www.ncbi.nlm.nih.gov/pubmed/1873324", "http://www.ncbi.nlm.nih.gov/pubmed/15773524", "http://www.ncbi.nlm.nih.gov/pubmed/18625105", "http://www.ncbi.nlm.nih.gov/pubmed/16637799", "http://www.ncbi.nlm.nih.gov/pubmed/18313197" ], "ideal_answer": [ "No data indicate causal connection between gastro esophageal/laryngopharyngeal(LPR) reflux disease and the occurrence of intraoral burning sensations" ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002054", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005764", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004941", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004935", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004942", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009059", "http://www.disease-ontology.org/api/metadata/DOID:8534", "http://www.disease-ontology.org/api/metadata/DOID:4331" ], "type": "yesno", "id": "5321ae889b2d7acc7e000006", "snippets": [ { "offsetInBeginSection": 1082, "offsetInEndSection": 1234, "text": "Our results suggest that there is no causal connection between LPR episodes and the occurrence of intraoral burning sensations in the examined patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21359587", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 803, "text": "As reported below, although this symptom may well be diagnostically misleading, careful diagnosis based on clinical signs may distinguish patients with BMS from those with reflux disease, and successful management of burning mouth is often enables.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15773524", "endSection": "abstract" } ] }, { "body": "Which is the protein (antigen) targeted by anti-Vel antibodies in the Vel blood group?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1823954", "http://www.ncbi.nlm.nih.gov/pubmed/14617316", "http://www.ncbi.nlm.nih.gov/pubmed/23505126", "http://www.ncbi.nlm.nih.gov/pubmed/1304158", "http://www.ncbi.nlm.nih.gov/pubmed/9745158", "http://www.ncbi.nlm.nih.gov/pubmed/6522937", "http://www.ncbi.nlm.nih.gov/pubmed/1703877", "http://www.ncbi.nlm.nih.gov/pubmed/12430675", "http://www.ncbi.nlm.nih.gov/pubmed/18598283", "http://www.ncbi.nlm.nih.gov/pubmed/20795312", "http://www.ncbi.nlm.nih.gov/pubmed/889425" ], "ideal_answer": [ "Disruption of SMIM1 causes the Vel- blood type. The protein carrying the Vel blood group antigen was biochemically purified from red blood cell membranes. Mass spectrometry-based de novo peptide sequencing identified this protein to be small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. Expression of SMIM1 cDNA in Vel- cultured cells generated anti-Vel cell surface reactivity, confirming that SMIM1 encoded the Vel blood group antigen. (PMID: 23505126)", "SMIM1" ], "exact_answer": [ "SMIM1" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001788", "http://www.disease-ontology.org/api/metadata/DOID:4176", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001789", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000941", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906" ], "type": "factoid", "id": "516545a8298dcd4e51000056", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Anti-Vel is an uncommon antibody to a high-prevalence antigen. Its clinical significance and management in the prenatal setting are not well characterized.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20795312", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Haemolytic disease of the newborn because of rare anti-Vel.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18598283", "endSection": "title" }, { "offsetInBeginSection": 474, "offsetInEndSection": 654, "text": "A haemolytic anti-Vel was detected in the tube test. In contrast, the particular commercial gel test kit used did not reveal the haemolytic property or specificity of the antibody.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9745158", "endSection": "sections.0" } ] }, { "body": "Which are the subtypes of Pfeiffer syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11556600", "http://www.ncbi.nlm.nih.gov/pubmed/19407629", "http://www.ncbi.nlm.nih.gov/pubmed/9475589", "http://www.ncbi.nlm.nih.gov/pubmed/8434615", "http://www.ncbi.nlm.nih.gov/pubmed/11807866", "http://www.ncbi.nlm.nih.gov/pubmed/15305355", "http://www.ncbi.nlm.nih.gov/pubmed/16740155", "http://www.ncbi.nlm.nih.gov/pubmed/9014285" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18471228", "o": "C537888" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18471228", "o": "Pfeiffer Mayer syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2931655", "o": "http://linkedlifedata.com/resource/umls/label/A18471228" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3572", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/918" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/918", "o": "http://www.dbpedia.org/resource/Pfeiffer_syndrome" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3572", "o": "Pfeiffer syndrome, 101600" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/918", "o": "Pfeiffer_syndrome" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3573", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/918" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3573", "o": "Pfeiffer syndrome, 101600" } ], "ideal_answer": [ "Pfeiffer syndrome is divided into three clinical subtypes.", "Pfeiffer syndrome is divided into three clinical subtypes. Type 1 \"classic\" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull." ], "exact_answer": [ [ "Type I", "Type I (1)" ], [ "Type II", "Type II (2)" ], [ "Type III", "Type III (3)" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016130", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.disease-ontology.org/api/metadata/DOID:14705", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000168" ], "type": "list", "id": "52bf1d6003868f1b0600000e", "snippets": [ { "offsetInBeginSection": 461, "offsetInEndSection": 691, "text": "Of 802 patients treated for craniosynostosis, 28 were identified with Pfeiffer syndrome: 17 were classified as type I (61 percent), seven were classified as type II (25 percent), and four were classified as type III (14 percent). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19407629", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 875, "text": "Pfeiffer syndrome is divided into three clinical subtypes. Type 1 \"classic\" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16740155", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 542, "text": "Recently, based on clinical findings, the disorder has been divided into three subtypes: type 1, characterized by mild expression; type 2, in which clover leaf skull deformity and multiple congenital anomalies are present at birth; and type 3, which is similar to type 2, but lacks the presence of the clover leaf skull at birth. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9014285", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 520, "text": "It is a clinically variable disorder and has been divided into three subtypes [Cohen, 1993: Am J Med Genet 45:300-307]. Type 1 represents the less severe cases, while types 2 and 3 are the more severe cases. These latter types tend to have a higher risk for neurodevelopmental problems and a reduced life expectancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9475589", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 1267, "text": "Classic Pfeiffer syndrome is designated type I. Type 2 consists of cloverleaf skull with Pfeiffer hands and feet together with ankylosis of the elbows. Such patients do poorly with an early death. All reported instances to date have been sporadic. Type 3 is similar to type 2 but without cloverleaf skull. Ocular proptosis is severe in degree and the anterior cranial base is markedly short. These patients also do poorly and tend to have an early death. To date all cases have occurred sporadically. Although these 3 clinical subtypes do not have status as separate entities, their diagnostic and prognostic implications are important. Type 1 is commonly associated with normal intelligence, generally good outcome, and can be found dominantly inherited in some families. Types 2 and 3 generally have severe neurological compromise, poor prognosis, early death, and sporadic occurrence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8434615", "endSection": "abstract" } ] }, { "body": "Is thrombophilia related to increased risk of miscarriage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11583310", "http://www.ncbi.nlm.nih.gov/pubmed/18845284", "http://www.ncbi.nlm.nih.gov/pubmed/16962918", "http://www.ncbi.nlm.nih.gov/pubmed/19135285", "http://www.ncbi.nlm.nih.gov/pubmed/22543699", "http://www.ncbi.nlm.nih.gov/pubmed/15027582", "http://www.ncbi.nlm.nih.gov/pubmed/7986734", "http://www.ncbi.nlm.nih.gov/pubmed/20860491", "http://www.ncbi.nlm.nih.gov/pubmed/22164918", "http://www.ncbi.nlm.nih.gov/pubmed/15713144", "http://www.ncbi.nlm.nih.gov/pubmed/19165673", "http://www.ncbi.nlm.nih.gov/pubmed/19031171", "http://www.ncbi.nlm.nih.gov/pubmed/21380983" ], "ideal_answer": [ "Thrombophilia has been found to be considerably more common in women with pregnancy-associated complications in comparison with the general population, and most frequently in conjunction with venous thromboembolism during pregnancy and the postpartum period. In particular there is an increased risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia. When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0007565", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018566", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011248", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019851", "http://www.disease-ontology.org/api/metadata/DOID:10591", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011255", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011256" ], "type": "yesno", "id": "513cdc38bee46bd34c000007", "snippets": [ { "offsetInBeginSection": 1065, "offsetInEndSection": 1159, "text": "Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22543699", "endSection": "sections.0" }, { "offsetInBeginSection": 571, "offsetInEndSection": 796, "text": "for illustrative purposes, a patient presenting with combined thrombophilia--both genetic and acquired--will be discussed. This patient had suffered severe gestational complications that led to devastating obstetrical outcome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22164918", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Thrombophilias have been implicated in complications related to ischemic placental disease including recurrent pregnancy loss, intrauterine fetal demise, preeclampsia, fetal growth restriction, placental abruption, and preterm delivery", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21380983", "endSection": "sections.0" }, { "offsetInBeginSection": 905, "offsetInEndSection": 1061, "text": "Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7986734", "endSection": "sections.0" }, { "offsetInBeginSection": 148, "offsetInEndSection": 263, "text": "Thrombotic risk during pregnancy and the puerperium is higher in asymptomatic women with than without thrombophilia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15027582", "endSection": "sections.0" }, { "offsetInBeginSection": 734, "offsetInEndSection": 870, "text": "Further studies are required to assess the thrombotic risk in women with preeclampsia as well as early or late recurrent pregnancy loss.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15027582", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11583310", "endSection": "title" }, { "offsetInBeginSection": 1265, "offsetInEndSection": 1532, "text": "In conclusion, homozygous carriers of factor V Leiden and, to a lesser extent, double heterozygous carriers of factor V Leiden and of the prothrombin mutation have an increased risk of venous thrombosis during pregnancy, particularly high during the postpartum period", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11583310", "endSection": "sections.0" }, { "offsetInBeginSection": 767, "offsetInEndSection": 873, "text": "Careful diagnosis, observation and monitoring can add significant benefit to LMWH therapy during pregnancy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19135285", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Pregnancy in healthy women is accompanied by hypercoagulable changes that may interact with thrombophilia risk factors and threaten pregnancy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19031171", "endSection": "sections.0" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1444, "text": "Fifty-three (13 %) women had antiphospholipid antibodies (lupus anticoagulant and/or anti-beta2-glycoprotein 1 antibodies) mainly associated with the risk of spontaneous abortion during the first trimester", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19031171", "endSection": "sections.0" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1713, "text": "thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the general population, and most frequently in conjunction with venous thromboembolism during pregnancy and the postpartum period", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19031171", "endSection": "sections.0" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1262, "text": "When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18845284", "endSection": "sections.0" }, { "offsetInBeginSection": 604, "offsetInEndSection": 779, "text": "knowledge combined with the appropriate use of thromboprophylaxis and treatment in women who have objectively confirmed VTE continue to improve maternal and perinatal outcomes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16962918", "endSection": "sections.0" }, { "offsetInBeginSection": 1508, "offsetInEndSection": 1666, "text": "The risk of having thrombophilia is doubled in men who have fathered pregnancies which ended in perinatal death as well as in the mothers of such pregnancies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15713144", "endSection": "sections.0" }, { "offsetInBeginSection": 560, "offsetInEndSection": 707, "text": "The prevalence of thrombophilic variants is of possible public health significance for other morbidity; but perhaps not in relation to preeclampsia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19165673", "endSection": "sections.0" }, { "offsetInBeginSection": 694, "offsetInEndSection": 826, "text": "This study suggests that thrombophilia \"mediates\" in lowering of cardiovascular risk factors in women with a history of preeclampsia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20860491", "endSection": "sections.0" } ] }, { "body": "Intact macromolecular assemblies are analysed by advanced mass spectrometry. How large complexes (in molecular weight) have been studied?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23064518", "http://www.ncbi.nlm.nih.gov/pubmed/8006040", "http://www.ncbi.nlm.nih.gov/pubmed/19140748", "http://www.ncbi.nlm.nih.gov/pubmed/16939266" ], "ideal_answer": [ "2.3 megadalton" ], "exact_answer": [ "2.3 megadalton" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043933", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046912", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013057", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046911", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0065003", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D021241", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0034621", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0032991", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008970", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0034622", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018629", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053719" ], "type": "factoid", "id": "514c3fd7d24251bc05000062", "snippets": [ { "offsetInBeginSection": 165, "offsetInEndSection": 354, "text": "Here we show that the Orbitrap mass analyzer can be used to measure protein assemblies of molecular weights approaching one megadalton with sensitivity down to the detection of single ions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23064518", "endSection": "sections.0" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1015, "text": "Using this relationship we show that we can determine masses of both 30S subunits and intact 2.3 MDa 70S ribosomes from Thermus thermophilus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16939266", "endSection": "sections.0" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1801, "text": "We confirm the existence of these subpopulations using tandem mass spectrometry of intact 30S subunits. Overall, the results show that, rather than uniform particles, gas-phase ribosomes consist of a number of discrete populations. More generally, the results establish a rigorous procedure for accurate mass measurement and spectral analysis of heterogeneous macromolecular assemblies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16939266", "endSection": "sections.0" } ] }, { "body": "What is targeted by Palbociclib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21815704", "http://www.ncbi.nlm.nih.gov/pubmed/21679088", "http://www.ncbi.nlm.nih.gov/pubmed/20197484", "http://www.ncbi.nlm.nih.gov/pubmed/25701171", "http://www.ncbi.nlm.nih.gov/pubmed/25636162", "http://www.ncbi.nlm.nih.gov/pubmed/21806477", "http://www.ncbi.nlm.nih.gov/pubmed/21109448", "http://www.ncbi.nlm.nih.gov/pubmed/24216225", "http://www.ncbi.nlm.nih.gov/pubmed/26045340", "http://www.ncbi.nlm.nih.gov/pubmed/23300028" ], "ideal_answer": [ "Necitumumab is a fully human IgG(1) monoclonal antibody directed at the epidermal growth factor receptor (EGFR). It is used for treatment of nonsmall cell lung cancer." ], "exact_answer": [ "epidermal growth factor receptor" ], "type": "factoid", "id": "56c1f01cef6e394741000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "BACKGROUND: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26045340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Epidermal growth factor receptor-directed monoclonal antibodies in nonsmall cell lung cancer: an update.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636162", "endSection": "title" }, { "offsetInBeginSection": 505, "offsetInEndSection": 762, "text": " A Southwest Oncology Group study currently prospectively evaluates the predictive biomarkers for cetuximab. In the SQUIRE phase III trial, necitumumab added to cisplatin and gemcitabine increased the survival in patients with advanced squamous cell NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701171", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1703, "text": "Numerous other drugs are in earlier stages of development for HNSCC treatment, including novel anti-EGFR mAbs (MEHD7945A, necitumumab, and RO5083945), small-molecule TKIs (vandetanib, icotinib, and CUDC-101), EGFR antisense, various add-on therapies to radiation and chemotherapy (bevacizumab, interleukin-12, lenalidomide, alisertib, and VTX-2337), and drugs (temsirolimus, everolimus, OSI-906, dasatinib, and PX-866) intended to overcome resistance to anti-EGFR agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24216225", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1233, "text": "Necitumumab, a fully human monoclonal antibody, is currently evaluated in combination with chemotherapy in two phase III trials in patients with advanced NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300028", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1291, "text": "Necitumumab is currently evaluated in combination with chemotherapy in two randomized phase III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Joining cetuximab, sorafenib, afatinib, intedanib, and crizotinib in phase III development for non-small cell lung cancer (NSCLC) are ramucirumab (developed by ImClone, a subsidiary of Lilly), necitumumab (developed by ImClone and Bristol-Myers Squibb), and tivantinib (ARQ 197, developed by ArQule and Daiichi Sankyo). Necitumumab is a second-generation anti-EGFR monoclonal antibody (mAb) similar to cetuximab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815704", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 564, "text": "Necitumunab is a fully human IgG1 monoclonal antibody targeting EGFR, having the potential benefit of lower hypersensitivity reaction risk as compared with cetuximab and also equivalent antibody-dependent cell-mediated cytotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Necitumumab, a monoclonal antibody directed against EGFR, is currently under development as a treatment for advanced NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21806477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "A phase I pharmacologic study of necitumumab (IMC-11F8), a fully human IgG1 monoclonal antibody directed against EGFR in patients with advanced solid malignancies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20197484", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "PURPOSE: This study aimed to determine a maximum tolerated dose (MTD) and recommended dose for disease-directed studies of necitumumab (IMC-11F8), a fully human IgG(1) monoclonal antibody directed at the epidermal growth factor receptor, and to characterize the safety profile, pharmacokinetics, preliminary antitumor activity, and immunogenicity of necitumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20197484", "endSection": "abstract" } ] }, { "body": "Which peptide plays a pivotal role in human cystatin C fibrillization?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25479090" ], "ideal_answer": [ "Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm developed in our lab. This peptide was synthesized and self-assembled into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization.", "Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm. This peptide was synthesized and self-assembled into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization." ], "exact_answer": [ "LQVVR" ], "concepts": [ "http://www.uniprot.org/uniprot/CYT_COTJA", "http://www.uniprot.org/uniprot/CYT_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015891", "http://www.uniprot.org/uniprot/CYT_MICIK", "http://www.biosemantics.org/jochem#4262068", "http://www.biosemantics.org/jochem#4262069", "http://www.uniprot.org/uniprot/CYT_NAJKA", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055316", "http://www.uniprot.org/uniprot/CYT_CYPCA" ], "type": "factoid", "id": "56b1f4300a360a5e4500001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 759, "text": "Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm developed in our lab. This peptide was synthesized and self-assembled into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The pentapeptide LQVVR plays a pivotal role in human cystatin C fibrillization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479090", "endSection": "title" }, { "offsetInBeginSection": 700, "offsetInEndSection": 780, "text": "the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479090", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 780, "text": "Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479090", "endSection": "abstract" } ] }, { "body": "What is ChiRP-seq (Chromatin Isolation by RNA Purification sequencing)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21963238" ], "ideal_answer": [ "ChiRP-seq (Chromatin Isolation by RNA Purification sequencing) is a method where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020411", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017421" ], "type": "summary", "id": "56af7b820a360a5e45000014", "snippets": [ { "offsetInBeginSection": 143, "offsetInEndSection": 1027, "text": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency toward the 3' end, peaking at CES sites. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lncRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1142, "text": "ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 575, "text": "ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 544, "text": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 345, "text": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 905, "offsetInEndSection": 1027, "text": "ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 462, "text": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1027, "text": "HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 462, "text": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Long noncoding RNAs (lncRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1033, "text": "ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 345, "text": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 462, "text": "ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract" } ] }, { "body": "What is the use of MammaPrint and Oncotype DX?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23573359", "http://www.ncbi.nlm.nih.gov/pubmed/23411384", "http://www.ncbi.nlm.nih.gov/pubmed/19101988", "http://www.ncbi.nlm.nih.gov/pubmed/19585214", "http://www.ncbi.nlm.nih.gov/pubmed/21998967", "http://www.ncbi.nlm.nih.gov/pubmed/20587405", "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "http://www.ncbi.nlm.nih.gov/pubmed/22359236", "http://www.ncbi.nlm.nih.gov/pubmed/23495982", "http://www.ncbi.nlm.nih.gov/pubmed/23462680", "http://www.ncbi.nlm.nih.gov/pubmed/21501481", "http://www.ncbi.nlm.nih.gov/pubmed/23337633" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17680439", "o": "MammaPrint" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2827401", "o": "http://linkedlifedata.com/resource/umls/label/A17680439" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10812803", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1709318", "o": "http://linkedlifedata.com/resource/umls/label/A10812803" } ], "ideal_answer": [ "The MammaPrint and Oncotype DX assays are used to predict breast cancer recurrence risk and guide adjuvant chemotherapy decisions." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045506" ], "type": "summary", "id": "5167d47e298dcd4e5100005e", "snippets": [ { "offsetInBeginSection": 122, "offsetInEndSection": 599, "text": "Molecular tests such as the 21 gene expression test (Oncotype DX(TM)) and 70 gene microarray test (MammaPrint(\u00ae)) have revolutionized the predictive and prognostic tools in the clinic. By stratifying the risk of recurrence for patients, the tests are able to provide clinicians with more information on the treatment outcomes of using chemotherapy, HER2 targeted therapy or endocrine therapy or the combination of the therapies for patients with particular genetic expressions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23573359", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 697, "text": "Gene expression profiling tests are used in an attempt to determine the right treatment for the right person with early-stage breast cancer that may have spread to nearby lymph nodes but not to distant parts of the body. These new diagnostic approaches are designed to spare people who do not need additional treatment (adjuvant therapy) the side effects of unnecessary treatment, and allow people who may benefit from adjuvant therapy to receive it. In the present review we discuss in detail the major diagnostic tests available such as MammaPrint dx, Oncotype dx, PAM50, Mammostrat, IHC4, MapQuant DX, Theros-Breast Cancer Gene Expression Ratio Assay, and their potential clinical applications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23462680", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Oncotype DX, PAM50, and MammaPrint are multigene tests that are being used clinically for early-stage breast cancer to predict recurrence risk and guide adjuvant chemotherapy decisions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23411384", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 504, "text": "We critically evaluated the available evidence on genomic tests in breast cancer to define their prognostic ability and likelihood to determine treatment benefit. METHODS: Independent evaluation of six genomic tests [Oncotype Dx\u2122, MammaPrint(\u00ae), Genomic Grade Index, PAM50 (ROR-S), Breast Cancer Index, and EndoPredict] was carried out by a panel of experts in three parameters: analytical validity, clinical validity, and clinical utility based on the principles of the EGAPP criteria. PANEL", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23337633", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 526, "text": "Gene expression profiling (GEP) is being used increasingly for risk stratification to identify women with lymph node-negative, estrogen receptor-positive, early stage breast cancer who are most likely to benefit from adjuvant chemotherapy. The authors of this report evaluated the cost effectiveness of recurrence score-guided treatment using 2 commercially available GEP tests, Oncotype DX (Genomic Health, Redwood City, Calif) and MammaPrint (Agendia Inc., Irvine, Calif), from a third-party payer's perspective.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22359236", "endSection": "sections.0" }, { "offsetInBeginSection": 128, "offsetInEndSection": 686, "text": "genomic tumor signatures that predict a patient's risk of breast cancer recurrence and response to chemotherapy. The paper builds on empirical evidence from the two trials to explore the emergence of diverse regulatory-scientific hybrids; that is, the paper discusses configurations of genomic practice and bioclinical work that depend on linkages between technical, commercial, patient, clinical, and legal interests and institutions. The development of the genomic signatures for each trial--Oncotype DX and MammaPrint--has followed quite different routes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21998967", "endSection": "sections.0" }, { "offsetInBeginSection": 1350, "offsetInEndSection": 1694, "text": "Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "endSection": "sections.0" }, { "offsetInBeginSection": 476, "offsetInEndSection": 903, "text": "We will review the primary tools in clinical use: Adjuvant!, Oncotype DX, and MammaPrint as well as intrinsic subtypes and the plans for their further assessment in the clinical trial setting. The expected benefit from these models are that treatment recommendations for women with early-stage breast cancer will become more individualized and thereby appropriate by combining standard clinicopathologic and molecular features.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20587405", "endSection": "sections.0" }, { "offsetInBeginSection": 559, "offsetInEndSection": 914, "text": "newer prognostic markers with a focus on the 21-gene recurrence score (Oncotype DX(\u2122)), 70-gene prognosis profile (Mammaprint(\u00ae)), and Adjuvant! Online. Conclusion: These techniques differ in their execution and application and have been demonstrated to provide further data on risk stratification as compared with conventional breast-cancer-risk factors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23495982", "endSection": "sections.0" }, { "offsetInBeginSection": 18, "offsetInEndSection": 496, "text": "diagnostic tools such as MammaPrint and oncotype-DX are beginning to have impact on clinical practice of breast cancer. They are based on gene expression profiling, i.e., gene expression analysis of a large number of genes. Their unique characteristic is the use of a score calculated from expression values of a number of genes, for which the Food and Drug Administration (FDA) created a new diagnostic category entitled \"in vitro diagnostic multivariate index assay (IVDMIA).\"", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19585214", "endSection": "sections.0" }, { "offsetInBeginSection": 699, "offsetInEndSection": 970, "text": "the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets, such as luminal A and B, basal, normal-like, and ERBB2+, and prognostic signatures including MammaPrint and Oncotype DX, predicted genomic instability in our samples.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19101988", "endSection": "sections.0" } ] }, { "body": "Does nifedipine inhibit L-type calcium channels?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16573711", "http://www.ncbi.nlm.nih.gov/pubmed/10320722", "http://www.ncbi.nlm.nih.gov/pubmed/10404034", "http://www.ncbi.nlm.nih.gov/pubmed/24752219", "http://www.ncbi.nlm.nih.gov/pubmed/24513517", "http://www.ncbi.nlm.nih.gov/pubmed/9388008", "http://www.ncbi.nlm.nih.gov/pubmed/17346891", "http://www.ncbi.nlm.nih.gov/pubmed/10900233", "http://www.ncbi.nlm.nih.gov/pubmed/9126675", "http://www.ncbi.nlm.nih.gov/pubmed/9399968", "http://www.ncbi.nlm.nih.gov/pubmed/12753410", "http://www.ncbi.nlm.nih.gov/pubmed/24680380", "http://www.ncbi.nlm.nih.gov/pubmed/11104511", "http://www.ncbi.nlm.nih.gov/pubmed/11273667", "http://www.ncbi.nlm.nih.gov/pubmed/18326812", "http://www.ncbi.nlm.nih.gov/pubmed/8647712", "http://www.ncbi.nlm.nih.gov/pubmed/16650887", "http://www.ncbi.nlm.nih.gov/pubmed/12205133", "http://www.ncbi.nlm.nih.gov/pubmed/8793089", "http://www.ncbi.nlm.nih.gov/pubmed/15350645", "http://www.ncbi.nlm.nih.gov/pubmed/9259470", "http://www.ncbi.nlm.nih.gov/pubmed/9882694", "http://www.ncbi.nlm.nih.gov/pubmed/23690182", "http://www.ncbi.nlm.nih.gov/pubmed/23200725", "http://www.ncbi.nlm.nih.gov/pubmed/25340466", "http://www.ncbi.nlm.nih.gov/pubmed/10805657", "http://www.ncbi.nlm.nih.gov/pubmed/17676593", "http://www.ncbi.nlm.nih.gov/pubmed/11726244", "http://www.ncbi.nlm.nih.gov/pubmed/10564356", "http://www.ncbi.nlm.nih.gov/pubmed/15335104", "http://www.ncbi.nlm.nih.gov/pubmed/15550786", "http://www.ncbi.nlm.nih.gov/pubmed/20432454", "http://www.ncbi.nlm.nih.gov/pubmed/19634509" ], "ideal_answer": [ "Yes, nifedipine is a typical blocker of L-type calcium channels." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4273755", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009543", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020746" ], "type": "yesno", "id": "56c313d150c68dd416000002", "snippets": [ { "offsetInBeginSection": 1319, "offsetInEndSection": 1540, "text": "Nifedipine, an L-type calcium channel blocker, reduced the expression of synaptogamin and syntaxin and blocked the suppressive effect of vecuronium, suggesting that both agents inhibit presynaptic L-type calcium channels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23200725", "endSection": "abstract" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1531, "text": "Treatment with nifedipine to inhibit calcium influx via the L-type channel Cav1.2 (alpha(1C)) inhibited the TGFbeta stimulated increase in ANK expression at all phases of chondrogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20432454", "endSection": "abstract" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1670, "text": "Finally, we found that PKCepsilon-induced stellation was significantly reduced by the specific L-type channel blocker nifedipine, indicating that calcium influx through VGCC mediates the change in astrocyte morphology induced by PKCepsilon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17676593", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 706, "text": "However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346891", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 818, "text": "Both the metallic ions Cd2+ and Ni2+, known to inhibit voltage-gated calcium channels and T-type channels, respectively, and verapamil and nifedipine, typical blocker of L-type calcium channels completely prevented the hypoxic neuronal NO generation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15350645", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1556, "text": "Further, the L-type calcium channel blocker, nifedipine, was able to inhibit the initial increase in [Ca2+]i, suggesting that at least this phase of the TMT effect was mediated by calcium channels, although nifedipine had no significant effect on the time to reach the maximal [Ca2+]i level", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8647712", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 931, "text": "Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12205133", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 950, "text": "Concentrations of nifedipine (10 microM) and nimodipine (3 microM) that maximally inhibit L-type calcium channels reduced the sI(AHP) by 30 and 50%, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10805657", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 1192, "text": "Consequently, it was demonstrated in the present study that nimodipine and nitrendipine inhibit both L- and N-type calcium channels and thus seem to be unique among the dihydropyridines examined in their effects on calcium channels in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells, whereas nifedipine and niguldipine appear to block mainly L-type calcium channels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9259470", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 705, "text": "However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346891", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 505, "text": "Calcium-channel antagonists, omega-conotoxin GVIA (omega-CgTx GVIA; N-type), nifedipine (L-type), and omega-conotoxin MVIIC (omega-CmTx MVIIC; P/Q type), were used to characterize the voltage-operated Ca(2+) channels (VOCCs) involved in this release", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11104511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The T- and L-type calcium channel blocker (CCB) mibefradil attenuates leg edema induced by the L-type CCB nifedipine in the spontaneously hypertensive rat: a novel differentiating assay.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18326812", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "L-type calcium channel antagonist nifedipine reduces neurofilament restitution following traumatic optic nerve injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15335104", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Nifedipine, an L-type calcium channel blocker, restores the hypnotic response in rats made tolerant to the alpha-2 adrenergic agonist dexmedetomidine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9399968", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Comparison of L-type calcium channel blockade by nifedipine and/or cadmium in guinea pig ventricular myocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10900233", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the involvement of L-type calcium channel blockers in epilepsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16573711", "endSection": "title" } ] }, { "body": "Is there any data to suggest that TRH (thyrotropin releasing hormone) administration can improve symptom severity of amyotrophic lateral sclerosis patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3148185", "http://www.ncbi.nlm.nih.gov/pubmed/3148186", "http://www.ncbi.nlm.nih.gov/pubmed/2497684", "http://www.ncbi.nlm.nih.gov/pubmed/2497685", "http://www.ncbi.nlm.nih.gov/pubmed/3091628", "http://www.ncbi.nlm.nih.gov/pubmed/3088700", "http://www.ncbi.nlm.nih.gov/pubmed/1596403", "http://www.ncbi.nlm.nih.gov/pubmed/7925318", "http://www.ncbi.nlm.nih.gov/pubmed/1469425", "http://www.ncbi.nlm.nih.gov/pubmed/2475830", "http://www.ncbi.nlm.nih.gov/pubmed/3146705", "http://www.ncbi.nlm.nih.gov/pubmed/3147318", "http://www.ncbi.nlm.nih.gov/pubmed/22017410", "http://www.ncbi.nlm.nih.gov/pubmed/3097367", "http://www.ncbi.nlm.nih.gov/pubmed/2982071", "http://www.ncbi.nlm.nih.gov/pubmed/8899662", "http://www.ncbi.nlm.nih.gov/pubmed/2514091", "http://www.ncbi.nlm.nih.gov/pubmed/3068777", "http://www.ncbi.nlm.nih.gov/pubmed/6134961", "http://www.ncbi.nlm.nih.gov/pubmed/2125610", "http://www.ncbi.nlm.nih.gov/pubmed/1579228", "http://www.ncbi.nlm.nih.gov/pubmed/1906441", "http://www.ncbi.nlm.nih.gov/pubmed/11681403", "http://www.ncbi.nlm.nih.gov/pubmed/1792854", "http://www.ncbi.nlm.nih.gov/pubmed/2563937", "http://www.ncbi.nlm.nih.gov/pubmed/2513155", "http://www.ncbi.nlm.nih.gov/pubmed/2127925", "http://www.ncbi.nlm.nih.gov/pubmed/2233870", "http://www.ncbi.nlm.nih.gov/pubmed/2518665", "http://www.ncbi.nlm.nih.gov/pubmed/3080693", "http://www.ncbi.nlm.nih.gov/pubmed/2126554", "http://www.ncbi.nlm.nih.gov/pubmed/3080694", "http://www.ncbi.nlm.nih.gov/pubmed/3080695", "http://www.ncbi.nlm.nih.gov/pubmed/2132051", "http://www.ncbi.nlm.nih.gov/pubmed/1904337", "http://www.ncbi.nlm.nih.gov/pubmed/3136230", "http://www.ncbi.nlm.nih.gov/pubmed/6439824", "http://www.ncbi.nlm.nih.gov/pubmed/3104820", "http://www.ncbi.nlm.nih.gov/pubmed/3923160", "http://www.ncbi.nlm.nih.gov/pubmed/3104750", "http://www.ncbi.nlm.nih.gov/pubmed/3104751", "http://www.ncbi.nlm.nih.gov/pubmed/9444487" ], "ideal_answer": [ "Yes, there are studies demonstrating that TRH (thyrotropin releasing hormone) administration can improve symptom severity of amyotrophic lateral sclerosis patients. However, some studies have failed to demonstrate symptom improvement following TRH administration.", "Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion. " ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4272308", "http://www.disease-ontology.org/api/metadata/DOID:332" ], "type": "yesno", "id": "54d76ac63706e89528000016", "snippets": [ { "offsetInBeginSection": 212, "offsetInEndSection": 514, "text": "These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in the treatment of brain and spinal injury, and CNS disorders like schizophrenia, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, Parkinson's disease, depression, shock and ischemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22017410", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 733, "text": "The Effect of TRH to correct the abnormal F responses in SSP might be consistent with effects of TRH to reduce spasticity in amyotrophic lateral sclerosis described previously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9444487", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1221, "text": "Agents undergoing therapeutic trials at present include CNTF, IGF1 glutamate antagonists, branched-chain amino acids and TRH analogue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7925318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Evidence that thyrotropin-releasing hormone (TRH) has prominent trophic effects on the motor system led to several negative therapeutic trials in amyotrophic lateral sclerosis, a disease of the motor system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1579228", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 1131, "text": "The results of the clinical evaluation at the beginning and end of the treatment as well as after patient follow up demonstrated that beneficial effects do not occur equally in all patients but rather are transitory and do not improve the natural evolution of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1596403", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 538, "text": "The neurological evaluation after acute TRH-T treatment showed an objective improvement in 3 of the 8.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1792854", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 568, "text": "The outcome of the study, in agreement with some and at variance with other studies, was that TRH induced a statistically significant neurological improvement in 17 of the 23 ALS patients but little or none in the other ALS patients and in patients with other neurological diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1906441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "[A case of amyotrophic lateral sclerosis with disturbance of vertical ocular movement responding to thyrotropin releasing hormone (TRH)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1904337", "endSection": "title" }, { "offsetInBeginSection": 629, "offsetInEndSection": 763, "text": "TRH injections resulted in improvement of disturbance of vertical ocular movement, but no effect was seen on the weakness of the limb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1904337", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "13 patients with amyotrophic lateral sclerosis (ALS) were treated with intravenous infusion of thyrotropin-releasing hormone (TRH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2127925", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 347, "text": "Similar improvements in speech, swallowing and in tongue and jaw movements were seen after iv and oral administration in nine, five and eight patients respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2126554", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 220, "text": "No clinical improvement was detected. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2125610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "A trial of Thyrotropin Releasing Hormone (TRH) 5.0 mg/kg body weight subcutaneously every other day for two weeks produced transient increased tone in muscles, along with other (side-) effects in patients with Amyotrophic Lateral Sclerosis (ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2514091", "endSection": "abstract" }, { "offsetInBeginSection": 1561, "offsetInEndSection": 1705, "text": "Although the mechanism is not known, several reports of the effectiveness of thyrotropin releasing hormone (TRH) in ALS were recently published.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2513155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Protirelin (thyrotropin-releasing hormone) appears to be a neuromodulator in the extrahypothalamic nervous system and has been suggested as an adjunct in the treatment of amyotrophic lateral sclerosis (ALS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2563937", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1437, "text": "Clinical studies have shown that response to TRH is state dependent, that is, it depends on whether the patient has bulbar or nonbulbar signs and is male or female. Future studies must take into consideration this state dependence as a specific feature of the pharmacological action of TRH and its analogues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2497685", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 617, "text": "Three of the studies showed a transient, statistically significant effect in at least some muscles. The two studies that demonstrated no such effect both used TRH in very small doses. It therefore seems reasonable to conclude that the effect of TRH in ALS is a definite, acute, and transient response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2497684", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 642, "text": "It was found that in only 3 out of 14 patients with moderately progressed disease no improvement was achieved, while in 11 cases the improvement was from 10 to 20%. However, the improvement was transient, and TRH treatment failed to stop the progression of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3146705", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 181, "text": "Only 3 patients noted subjective improvement of strength.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3148186", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 348, "text": "In 6 of the 9, TRH induced a significant increase in vibratory inhibition. This suggests that the TRH-induced reduction of spasticity might be due to an increase in presynaptic inhibition acting on Ia fibres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3148185", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 446, "text": "However, 2 mg DN-1417, IM twice a day for 1 month in an open-label trial, produced no objective improvement of strength in nine patients with ALS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3104820", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 623, "text": "Our experience suggests that this approach is safe, has high patient acceptance, and is worthy of more careful evaluation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3104751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "Focal, small-to-moderate and transient improvement occurred in the muscle strength and function of patients with ALS who received TRH in dose-response and screening studies. In a small pilot study of 12 patients, 3 months administration of TRH at 10 mg per kg on alternate days resulted in localized increased strength of jaw muscles as well as significant improvement in lower extremity function. Aerobic exercise capacity was particularly improved in patients with ALS following administration of TRH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3104750", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 412, "text": "Mild to moderate improvement was found in 9 (56%) of 16 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3097367", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 653, "text": "We thought such action of TRH to be useful to the therapy of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3097367", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1011, "text": "With daily TRH, 10 patients noted subjective improvement without objective evidence, and 10 patients complained of worsening of the disease with objective decline after TRH was stopped. Statistical analysis, however, showed no beneficial effects from either acute or chronic TRH trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3080695", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 576, "text": "A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3080694", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 910, "text": "Nevertheless, statistically significant improvement was seen only in dynametric strength 1 hour after subcutaneous injection (p less than 0.05). Significant improvement occurred, in one patient only, on subjective speech testing during IV infusion of TRH. In none of six other ratings was there a significant difference between TRH and placebo. Subjective improvement was noted by 11 of 12 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3080693", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 607, "text": "Significant improvement, as shown by statistical analysis, was noted in muscle strength in the 9 patients by 5 infusions over a 4-week period and a sub-group of 5 patients treated by 8 infusions over 10 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3088700", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 291, "text": "The progressive course of this disease, manifested by increasing atrophy, paralysis and disability score, was not altered. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3923160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 479, "text": "Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6134961", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 502, "text": "Aerobic exercise capacity was particularly improved in patients with ALS following administration of TRH", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3104750", "endSection": "abstract" } ] }, { "body": "How can DUF families be deciphered?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22629278", "http://www.ncbi.nlm.nih.gov/pubmed/24237627", "http://www.ncbi.nlm.nih.gov/pubmed/23104832", "http://www.ncbi.nlm.nih.gov/pubmed/24901469", "http://www.ncbi.nlm.nih.gov/pubmed/25010333", "http://www.ncbi.nlm.nih.gov/pubmed/19787035", "http://www.ncbi.nlm.nih.gov/pubmed/23516388", "http://www.ncbi.nlm.nih.gov/pubmed/23572527", "http://www.ncbi.nlm.nih.gov/pubmed/25044324" ], "ideal_answer": [ "The genome projects have unearthed an enormous diversity of genes of unknown function that are still awaiting biological and biochemical characterization. These genes, as most others, can be grouped into families based on sequence similarity. The PFAM database currently contains over 2,200 such families, referred to as domains of unknown function (DUF). \nCritically examining domain covariation across metagenomic datasets can grant new perspectives on the roles and associations of DUFs in an ecological setting. Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge. \nIn a coordinated effort, the four large-scale centers of the NIH Protein Structure Initiative have determined the first three-dimensional structures for more than 250 of these DUF families." ], "type": "summary", "id": "5709f646cf1c325851000021", "snippets": [ { "offsetInBeginSection": 549, "offsetInEndSection": 753, "text": " These families include proteins with domain of unknown function (DUF) DUF23, DUF246, and DUF266. The evidence for these proteins being GTs and their possible roles in cell wall biosynthesis is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22629278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "The genome projects have unearthed an enormous diversity of genes of unknown function that are still awaiting biological and biochemical characterization. These genes, as most others, can be grouped into families based on sequence similarity. The PFAM database currently contains over 2,200 such families, referred to as domains of unknown function (DUF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19787035", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 545, "text": "In a coordinated effort, the four large-scale centers of the NIH Protein Structure Initiative have determined the first three-dimensional structures for more than 250 of these DUF families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19787035", "endSection": "abstract" }, { "offsetInBeginSection": 1768, "offsetInEndSection": 2165, "text": "Critically examining domain covariation across metagenomic datasets can grant new perspectives on the roles and associations of DUFs in an ecological setting. Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Crystal structures of three members (BACOVA_00364 from Bacteroides ovatus, BACUNI_03039 from Bacteroides uniformis and BACEGG_00036 from Bacteroides eggerthii) of the Pfam domain of unknown function (DUF4488) were determined to 1.95, 1.66, and 1.81 \u00c5 resolutions, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 847, "text": "Bacterial species in the Enterobacteriaceae typically contain multiple paralogues of a small domain of unknown function (DUF1471) from a family of conserved proteins also known as YhcN or BhsA/McbA. Proteins containing DUF1471 may have a single or three copies of this domain. Representatives of this family have been demonstrated to play roles in several cellular processes including stress response, biofilm formation, and pathogenesis. We have conducted NMR and X-ray crystallographic studies of four DUF1471 domains from Salmonella representing three different paralogous DUF1471 subfamilies: SrfN, YahO, and SssB/YdgH (two of its three DUF1471 domains: the N-terminal domain I (residues 21-91), and the C-terminal domain III (residues 244-314)). Notably, SrfN has been shown to have a role in intracellular infection by Salmonella Typhimurium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25010333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "Domain of unknown function (DUF) proteins represent a number of gene families that encode functionally uncharacterized proteins in eukaryotes. For example, DUF1618 family members in plants possess a 56-199-amino acid conserved domain and this family has not been described previously. Here, we report the characterization of 121 DUF1618 genes identified in the rice genome. Based on phylogenetic analysis, the rice DUF1618 family was divided into two major groups, each group consisting of two clades. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24237627", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 352, "text": "In this study we identified that a plant specific domain of unknown function, DUF581 is a zf-FCS type zinc finger. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24901469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "DUF2233, a domain of unknown function (DUF), is present in many bacterial and several viral proteins and was also identified in the mammalian transmembrane glycoprotein N-acetylglucosamine-1-phosphodiester \u03b1-N-acetylglucosaminidase (\"uncovering enzyme\" (UCE)). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23572527", "endSection": "abstract" } ] }, { "body": "Which genes does thyroid hormone receptor beta1 regulate in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19171649", "http://www.ncbi.nlm.nih.gov/pubmed/21149577", "http://www.ncbi.nlm.nih.gov/pubmed/9927321", "http://www.ncbi.nlm.nih.gov/pubmed/19629520", "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "http://www.ncbi.nlm.nih.gov/pubmed/17317766" ], "ideal_answer": [ "\u03b2-MHC, HCN4, KCND2/3, SERCA, TRbeta1, alpha-MHC" ], "exact_answer": [ [ "\u03b2-MHC" ], [ "HCN4" ], [ "KCND2/3" ], [ "SERCA" ], [ "TRbeta1" ], [ "alpha-MHC" ] ], "concepts": [ "http://www.uniprot.org/uniprot/THB_PAROL" ], "type": "list", "id": "515c4f1f298dcd4e51000007", "snippets": [ { "offsetInBeginSection": 959, "offsetInEndSection": 1079, "text": "we identified thyroid hormone receptor \u03b21 (TR\u03b21), which negatively regulates \u03b2-MHC transcription, as a target of miR-27a", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149577", "endSection": "sections.0" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1239, "text": "HCN2 gene expression was not significantly affected by TR beta 1. TR beta 1 exclusively suppressed HCN4 transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19629520", "endSection": "sections.0" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1010, "text": "TRalpha1 increased I(to), while TRbeta1 significantly reduced I(to) in size, which was associated with TRalpha1-mediated increase and TRbeta1-mediated reduction of KCND2/3 transcription.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19171649", "endSection": "sections.0" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1392, "text": "he TRbeta1 aporeceptor suppressed KCND3 expression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19171649", "endSection": "sections.0" }, { "offsetInBeginSection": 1651, "offsetInEndSection": 1792, "text": "increasing TR expression in the hypertrophied heart is associated with an improvement in contractile function and increased SERCA expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17317766", "endSection": "sections.0" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1373, "text": "TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "endSection": "sections.0" }, { "offsetInBeginSection": 75, "offsetInEndSection": 288, "text": "Our study investigates both the regulation of cardiac-specific genes and contractile behavior of the heart in the presence of a mutant thyroid hormone receptor beta1 (T3Rbeta1-delta337T) derived from the S kindred", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9927321", "endSection": "sections.0" }, { "offsetInBeginSection": 698, "offsetInEndSection": 939, "text": "The messenger RNA levels for MHC alpha and SERCA2 were markedly down-regulated, MHC beta messenger RNA was up-regulated. Although T3 levels were normal in these animals, this pattern of cardiac gene expression mimics a hypothyroid phenotype.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9927321", "endSection": "sections.0" } ] }, { "body": "Can siRNA affect response to afatinib treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23266614", "http://www.ncbi.nlm.nih.gov/pubmed/22436374", "http://www.ncbi.nlm.nih.gov/pubmed/23555954" ], "ideal_answer": [ "When afatinib was combined with an EGFR-specific siRNA there was a strong biological effect on growth inhibition and induction of apoptosis." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030422", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034741", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090065" ], "type": "yesno", "id": "54297ed2289fd6cb07000001", "snippets": [ { "offsetInBeginSection": 619, "offsetInEndSection": 812, "text": "On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555954", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1002, "text": "These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555954", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1280, "text": "Among the anti-EGFR agents tested, the strongest biological effect was observed when afatinib was combined with T790M-specific-siRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23266614", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1752, "text": "The combination of a potent, irreversible kinase inhibitor such as afatinib, with T790M-specific-siRNAs should be further investigated as a new strategy in the treatment of lung cancer containing the resistant T790M mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23266614", "endSection": "abstract" }, { "offsetInBeginSection": 2418, "offsetInEndSection": 2517, "text": "The strongest biological effect was observed when afatinib was combined with an EGFR-specific siRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22436374", "endSection": "abstract" }, { "offsetInBeginSection": 2175, "offsetInEndSection": 2417, "text": "The addition of EGFR siRNA to either TKIs or cetuximab additively enhanced growth inhibition and induction of apoptosis in all five cell lines, independent of the EGFR mutation status (wild-type or sensitizing mutation or resistant mutation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22436374", "endSection": "abstract" }, { "offsetInBeginSection": 2934, "offsetInEndSection": 3205, "text": "The combination of a potent, irreversible kinase inhibitor such as afatinib, with EGFR-specific siRNAs should be further investigated as a new strategy in the treatment of lung cancer and other EGFR dependent cancers, including those with downstream resistance mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22436374", "endSection": "abstract" } ] }, { "body": "What is the gold standard treatment for Iatrogenic male incontinence?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17982750", "http://www.ncbi.nlm.nih.gov/pubmed/19296976", "http://www.ncbi.nlm.nih.gov/pubmed/20877609", "http://www.ncbi.nlm.nih.gov/pubmed/23259418" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10807588", "o": "C50597" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1708460", "o": "http://linkedlifedata.com/resource/umls/label/A10807588" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1708460", "o": "http://linkedlifedata.com/resource/umls/label/A10807588" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10807588", "o": "Iatrogenic Lesion" } ], "ideal_answer": [ "The artificial urethral sphincter has represented, until today, the gold standard but, in the recent years, sling systems have been investigated as minimally invasive alternative options." ], "exact_answer": [ "Artificial urethral sphincter", "AUS" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014549", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013521", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053825", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014550", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052801", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007049" ], "type": "factoid", "id": "5325fdf0600967d132000001", "snippets": [ { "offsetInBeginSection": 315, "offsetInEndSection": 779, "text": "The initial treatment for SUI that persists after 12 months consists of conservative measures such as pelvic floor muscle exercises and behavioral therapy. Properly selected and informed patients can also be treated efficiently with minimally invasive procedures such as the implantation of a male suburethral sling, although the experience with such devices is not extensive. However, the implantation of artificial urinary sphincter is the gold standard therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259418", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 557, "text": "treatments such as periurethral injection of bulking agents, artificial urinary sphincter (AUS) implantation, and sub-urethral sling positioning. The artificial urethral sphincter has represented, until today, the gold standard but, in the recent years, sling systems have been investigated as minimally invasive alternative options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20877609", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 686, "text": "Today, three different sling procedures are commonly performed: bone-anchored, readjustable, and trans-obturator slings systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20877609", "endSection": "abstract" }, { "offsetInBeginSection": 1782, "offsetInEndSection": 1981, "text": "The bone anchored suburethral synthetic sling is a simple and attractive procedure that can produce immediate good results with low morbidity, especially when strictly selected patients are treated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19296976", "endSection": "abstract" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1712, "text": "BAUS implantation is a safe, effective, minimally invasive option for iatrogenic male incontinence due to ISD. It compares favourably with AUS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17982750", "endSection": "abstract" } ] }, { "body": "Which is the main CHEK2 genetic variant, thought to be involved in familial breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16998506", "http://www.ncbi.nlm.nih.gov/pubmed/17721994", "http://www.ncbi.nlm.nih.gov/pubmed/12610780", "http://www.ncbi.nlm.nih.gov/pubmed/14618615", "http://www.ncbi.nlm.nih.gov/pubmed/19763819" ], "ideal_answer": [ "CHEK2 1100delC mutation is recurrently detected in the general population and is thought to confer a moderate risk for breast cancer." ], "exact_answer": [ "CHEK2 1100delC mutation" ], "type": "factoid", "id": "5357b36cf1005d6b58000006", "snippets": [ { "offsetInBeginSection": 560, "offsetInEndSection": 654, "text": "the two most studied breast cancer-predisposing variants of the CHEK2 gene, 1100delC and I157T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17721994", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 904, "text": "The germline CHEK2-1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early-onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17721994", "endSection": "abstract" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1145, "text": "1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17721994", "endSection": "abstract" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1830, "text": "Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically- and geographically-selected populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17721994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12610780", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12610780", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1131, "text": "These results indicate that 1100delC may be the only CHEK2 allele that makes an appreciable contribution to breast cancer susceptibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12610780", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 781, "text": "CHEK2_1100delC was found in 5/903 (0.5%) breast cancer cases compared to 1/1016 (0.1%) controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19763819", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 446, "text": "Recently, the CHEK 2 gene, involved in DNA damage and replication checkpoints, has been pointed out as a good candidate; moreover, a specific variant in this gene,1100delC, has been found to increase breast cancer susceptibility among familial breast cancer cases not attributable to mutations in BRCA1 or BRCA2 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14618615", "endSection": "abstract" } ] }, { "body": "Is there an association between presenteeism and depression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15804203", "http://www.ncbi.nlm.nih.gov/pubmed/21669372", "http://www.ncbi.nlm.nih.gov/pubmed/14665817", "http://www.ncbi.nlm.nih.gov/pubmed/20726684", "http://www.ncbi.nlm.nih.gov/pubmed/25539872", "http://www.ncbi.nlm.nih.gov/pubmed/25173795", "http://www.ncbi.nlm.nih.gov/pubmed/20073388", "http://www.ncbi.nlm.nih.gov/pubmed/22532849", "http://www.ncbi.nlm.nih.gov/pubmed/21880374", "http://www.ncbi.nlm.nih.gov/pubmed/22261652", "http://www.ncbi.nlm.nih.gov/pubmed/25435902", "http://www.ncbi.nlm.nih.gov/pubmed/16282870", "http://www.ncbi.nlm.nih.gov/pubmed/19339899", "http://www.ncbi.nlm.nih.gov/pubmed/24854252", "http://www.ncbi.nlm.nih.gov/pubmed/20953117", "http://www.ncbi.nlm.nih.gov/pubmed/17156851", "http://www.ncbi.nlm.nih.gov/pubmed/16989105", "http://www.ncbi.nlm.nih.gov/pubmed/21220078", "http://www.ncbi.nlm.nih.gov/pubmed/20715299", "http://www.ncbi.nlm.nih.gov/pubmed/23244804", "http://www.ncbi.nlm.nih.gov/pubmed/15951705", "http://www.ncbi.nlm.nih.gov/pubmed/15572564", "http://www.ncbi.nlm.nih.gov/pubmed/22856386", "http://www.ncbi.nlm.nih.gov/pubmed/23439268", "http://www.ncbi.nlm.nih.gov/pubmed/21525074", "http://www.ncbi.nlm.nih.gov/pubmed/11329394", "http://www.ncbi.nlm.nih.gov/pubmed/25211435" ], "ideal_answer": [ "Yes. Presenteeism is associated with depression. Remission of depression is associated with improvement of presenteeism." ], "exact_answer": "yes", "type": "yesno", "id": "54f49e56d0d681a040000004", "snippets": [ { "offsetInBeginSection": 665, "offsetInEndSection": 806, "text": "Presenteeism was positively associated with severity of depression (Health and Work Performance Questionnaire, P < 0.0001; WPAI, P < 0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23439268", "endSection": "abstract" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1524, "text": "Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244804", "endSection": "abstract" }, { "offsetInBeginSection": 1765, "offsetInEndSection": 1867, "text": "Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244804", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 826, "text": "Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22856386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND: Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22532849", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 393, "text": "Two major causes of worker presenteeism (reduced on-the-job productivity as a result of health problems) are musculoskeletal pain and mental health issues, particularly depression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261652", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1555, "text": " Pain and depression were significantly associated with presenteeism. Pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261652", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 734, "text": "Survey adjusted multivariable logistic regression assessed classification of 12-month, depression-related presenteeism on the basis of socio-demographic, financial, work and health factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880374", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 982, "text": "RESULTS: The LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21669372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND: Depression is reported to be a major cause of illness-related sub-optimal work performance (presenteeism). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21525074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND: It is amply documented that mood disorders adversely affect job satisfaction, workforce productivity, and absenteeism/presenteeism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21220078", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 857, "text": "The difference in productivity loss due to impaired presenteeism was significantly different between the two groups, but the productivity loss due to absenteeism was not. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20953117", "endSection": "abstract" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1486, "text": "Disease activity (OR 3.24, 95% CI 1.11-9.48) and depression (OR 3.22, 95% CI 1.22-8.48) were associated with absenteeism, while depression (OR 5.69, 95% CI 1.77-18.27, disease activity (OR 3.97, 95% CI 1.76-8.98), anxiety (OR 3.90, 95% CI 1.83-8.31), self-efficacy (OR 0.71, 95% CI 0.58-0.86), and increasing age (OR 1.04 per year, 95% CI 1.00-1.08) were associated with presenteeism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20726684", "endSection": "abstract" }, { "offsetInBeginSection": 1696, "offsetInEndSection": 1853, "text": "Depression, in particular, appears to be associated with employment, absenteeism, and presenteeism, and should therefore be prioritized in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20726684", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 702, "text": "Depression frequently causes unemployment, absenteeism, and presenteeism, which results in significantly reduced productivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20715299", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 1239, "text": "Presenteeism and absenteeism were significantly worse for the depression group at each time point (p < or = .001). In cross-sectional models, presenteeism was associated with more severe depression symptoms, poorer general physical health, psychologically demanding work, the interaction ofpsychologically demanding work with depression, and less job control (r2 range = .33-.54).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20073388", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 900, "text": "Chronic conditions such as depression/anxiety, obesity, arthritis, and back/neck pain are especially important causes of productivity loss. Comorbidities have significant non-additive effects on both absenteeism and presenteeism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339899", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 841, "text": "RESULTS: At baseline, all presenteeism measures were sensitive to differences between those with (N=69) and without (N=363) depression/anxiety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17156851", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1548, "text": "Depression and anxiety were more consistently associated with \"presenteeism\" (that is, lost productivity while at work) than with absenteeism, whether this was measured by cutback days or by direct questionnaires.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16989105", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 687, "text": "RESULTS: Substantial research exists about anxiety and depression costs, such as performance and productivity, absenteeism, presenteeism, disability, physical disability exacerbation, mental health treatment, increased medical care costs, exacerbating of physical illness, and studies of mental health care limitations and cost-offset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16282870", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 507, "text": "The author discusses the etiology and potential solutions for managing this new component in the productivity equation and in addressing depression, the major contributor to presenteeism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951705", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1217, "text": "For employees who are currently depressed, recent research evidence has demonstrated that pharmacotherapy can have a dramatic and positive effect on lost productivity, absenteeism, and presenteeism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15804203", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1098, "text": "Among participants who were still employed, those with depression had significantly more job turnover, presenteeism, and absenteeism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15572564", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 870, "text": "Only depression affected both absenteeism-presenteeism and critical incidents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14665817", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1453, "text": "CONCLUSIONS: Depressive disorders in the workplace persist over time and have a major effect on work performance, most notably on \"presenteeism,\" or reduced effectiveness in the workplace. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11329394", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 596, "text": "The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25539872", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1300, "text": "The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z\u2009=\u2009-3.29, p\u2009=\u20090.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25435902", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 880, "text": "Depression in workers leads to significant absenteeism, \"presenteeism\" (diminished capacity due to illness while still present at work), and significantly increased medical expenses in addition to the costs of psychiatric care. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25211435", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1371, "text": "Significant predictors of presenteeism and activity impairment at follow-up (controlled for gender, age, spondyloarthritis subgroups and presenteeism at baseline) were presenteeism at baseline, poor quality of life, worse disease activity, decreased physical function, lower self-efficacy pain and symptom, higher scores of anxiety, depression, smoking and low education level, and for activity impairment also female sex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25173795", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1513, "text": "\" Pain and depression were significantly associated with presenteeism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22261652", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 869, "text": "Only depression affected both absenteeism-presenteeism and critical incidents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14665817", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 825, "text": "Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22856386", "endSection": "abstract" } ] }, { "body": "Which hormone abnormalities are common in Williams syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23734615", "http://www.ncbi.nlm.nih.gov/pubmed/18204753", "http://www.ncbi.nlm.nih.gov/pubmed/10378390", "http://www.ncbi.nlm.nih.gov/pubmed/15751610", "http://www.ncbi.nlm.nih.gov/pubmed/16181239", "http://www.ncbi.nlm.nih.gov/pubmed/22719898", "http://www.ncbi.nlm.nih.gov/pubmed/20425788", "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "http://www.ncbi.nlm.nih.gov/pubmed/15108207", "http://www.ncbi.nlm.nih.gov/pubmed/3164411", "http://www.ncbi.nlm.nih.gov/pubmed/17188616", "http://www.ncbi.nlm.nih.gov/pubmed/1867260", "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "http://www.ncbi.nlm.nih.gov/pubmed/16596673", "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "http://www.ncbi.nlm.nih.gov/pubmed/8835601" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/keywords/856", "o": "http://purl.uniprot.org/keywords/9995" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/856", "o": "Williams-Beuren syndrome" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/9995", "o": "Disease" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/856", "o": "WBS" }, { "p": "http://purl.uniprot.org/core/category", "s": "http://purl.uniprot.org/keywords/856", "o": "http://purl.uniprot.org/keywords/9995" } ], "ideal_answer": [ "Elevated Thyrotropin - TSH\nLow FT4\nGrowth Hormone deficiency\nCalcitonin deficiency\nElevated Prolactin\nElevated Cortisol\nElevated Oxytocin\nElevated Vasopressin" ], "exact_answer": [ [ "Elevated Thyrotropin -", "Elevated TSH" ], [ "Low FT4", "Low Thyroxine" ], [ "Growth Hormone deficiency", "GHD" ], [ "Calcitonin deficiency" ], [ "Elevated Prolactin" ], [ "Elevated Cortisol" ], [ "Elevated Oxytocin", "Elevated OT" ], [ "Elevated Vasopressin", "Elevated AVP" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018980" ], "type": "list", "id": "52f88d292059c6d71c000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 microU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 615, "text": "TSH response to thyrotropin-releasing hormone (TRH) injection (200 microg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6-2.2].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10405448", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 411, "text": "We report a boy with confirmed Williams-Beuren syndrome, who was found to have classical growth hormone deficiency and responded well to growth hormone therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10378390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 487, "text": "A 31-year-old man who had been under regular hemodialysis for 6 months was diagnosed as Williams syndrome (WS) by fluorescence in situ hybridization (FISH) chromosomal analysis. The association of WS and chronic renal failure (CRF) is only rarely encountered. Endocrinological examinations revealed hypergonadotropic hypogonadism. Prolonged and exaggerated responses of adrenocorticotropin (ACTH) to insulin-induced hypoglycemia and corticotropin releasing hormone (CRH) were also noted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8835601", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 507, "text": "Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1867260", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 220, "text": "It has been suggested that a defect in calcitonin function may play a role in Williams syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3164411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Imparied calcitonin secretion in patients with Williams syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "endSection": "title" }, { "offsetInBeginSection": 148, "offsetInEndSection": 510, "text": "in patients with Williams syndrome, we studied five such children, with intravenous calcium and parathyroid hormone infusions as provocative stimuli. These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 988, "text": "Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4056970", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 418, "text": "A 16-year-old male adolescent diagnosed to have the Williams-Beuren syndrome was referred to our obesity outpatient clinic, due to his morbid obesity (body mass index 39.2 kilograms per square metre) and gluttony. After several unsuccessful dietary treatments, we started therapy with sibutramine. As growth hormone (GH) deficiency was diagnosed by an additional GH-stimulation test, we commenced with a GH-treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18204753", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1065, "text": " Subclinical hypothyroidism is a frequent but stable finding in young children with WS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17188616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Thyroid involvement in Williams syndrome (WS) was recently reported in two small groups of patients, both showing an increased prevalence of elevation of TSH serum concentration; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596673", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 791, "text": "in a population of 95 WS patients, half of them followed for more than 5 years. Our study confirms the increased incidence of both elevated TSH serum values (37.9% in our sample)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596673", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1255, "text": "This study confirms the presence of alterations of thyroid function in WS ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16181239", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 463, "text": "We report a female infant with confirmed WBS who, through provocative testing, was found to have GHD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15751610", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 971, "text": "the elevated levels of prolactin and the response of hGH to growth hormone releasing hormone (GHRH) administration are indicative of a hypothalamic rather than pituitary defect. In conclusion, GH deficiency might contribute to the growth failure in a number of patients with WBS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15751610", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 455, "text": " a female presenting with congenital heart defects, liver hemangiomas, and facial dysmorphisms admitted to hospital at 3 months of age because of feeding difficulties and poor growth. She had hypotonia and large tongue, \"coarse\" face, and umbilical hernia in presence of complex congenital cardiovascular malformations. In spite of normal neonatal screening we performed serum levels of thyroid hormones. Thyrotropin level was very high ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108207", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 488, "text": "WS and TD participants had similar profiles in a familiar setting, while participants with WS had elevated cortisol late in the day in the novel setting when social demands were higher. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23734615", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 692, "text": "Results suggest that adults with WS have a typical diurnal cortisol profile ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23734615", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1096, "text": "Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22719898", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 646, "text": "high prevalence of impaired glucose regulation, adults with WS ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20425788", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 643, "text": "Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a low FT(4) concentration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "endSection": "abstract" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1099, "text": "WBS and abnormalities of thyroid function are common in patients with this feature. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824871", "endSection": "abstract" } ] }, { "body": "What is the treatment of choice for gastric lymphoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15213617", "http://www.ncbi.nlm.nih.gov/pubmed/15672765", "http://www.ncbi.nlm.nih.gov/pubmed/7975766", "http://www.ncbi.nlm.nih.gov/pubmed/22368024", "http://www.ncbi.nlm.nih.gov/pubmed/9667473", "http://www.ncbi.nlm.nih.gov/pubmed/10796047", "http://www.ncbi.nlm.nih.gov/pubmed/1377459", "http://www.ncbi.nlm.nih.gov/pubmed/15916100", "http://www.ncbi.nlm.nih.gov/pubmed/11682961", "http://www.ncbi.nlm.nih.gov/pubmed/11054376", "http://www.ncbi.nlm.nih.gov/pubmed/7978750", "http://www.ncbi.nlm.nih.gov/pubmed/3178044" ], "ideal_answer": [ "The treatment of choice for localized primary GI lymphoma is controversial. Complete surgical resection may increase the chance of complete remission, but mortality and relapse rates might be higher than those observed with combination chemotherapy alone.\nIn early stages of disease, H. pylori eradication alone may lead to complete lymphoma remission in up to 75% of cases. Nonresponder or locally advanced lymphoma should be treated with radiation therapy." ], "type": "summary", "id": "5509ba931180f13250000001", "snippets": [ { "offsetInBeginSection": 1169, "offsetInEndSection": 1242, "text": "The treatment of choice should be comprehensive therapy based on surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22368024", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1395, "text": "The treatment of choice for localized primary GI lymphoma is controversial. Complete surgical resection may increase the chance of complete remission, but mortality and relapse rates might be higher than those observed with combination chemotherapy alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15916100", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 219, "text": "The most common gastric lymphoma are low-grade marginal zone B-cell lymphoma (MZBCL) of MALT type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15672765", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 646, "text": "In early stages of disease, H. pylori eradication alone may lead to complete lymphoma remission in up to 75% of cases. Nonresponder or locally advanced lymphoma should be treated with radiation therapy. Advanced lymphoma may be treated with the nucleoside analogon cladribine within clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15672765", "endSection": "abstract" }, { "offsetInBeginSection": 1746, "offsetInEndSection": 2064, "text": "In patients with primary gastric diffuse large cell lymphoma and aggressive histology, diffuse large cell lymphoma in early stage SCT achieved good results, but surgery was associated with some cases of lethal complications. Thus it appears that CT should be considered the treatment of choice in this patient setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15213617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Controversy remains regarding the best treatment for primary gastric lymphoma (PGL). Recent developments in diagnosis and chemotherapy have changed strategies for this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11682961", "endSection": "abstract" }, { "offsetInBeginSection": 1602, "offsetInEndSection": 1798, "text": "With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11054376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "The treatment of primary gastric lymphoma is controversial. The role of surgery has come to be questioned with increasing knowledge about the pathogenesis of gastric lymphoma and with new therapeutic approaches such as eradication of Helicobacter pylori.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10796047", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1108, "text": "curative resection is the treatment of choice for gastric lymphoma, but radiation therapy may offer some benefit when complete resection is not feasible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1377459", "endSection": "abstract" } ] }, { "body": "Which assays can be used for detecting DNA fragmentation resulting from programmed cell death (apoptosis)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10623423", "http://www.ncbi.nlm.nih.gov/pubmed/10069565", "http://www.ncbi.nlm.nih.gov/pubmed/18265108", "http://www.ncbi.nlm.nih.gov/pubmed/1657218", "http://www.ncbi.nlm.nih.gov/pubmed/16839211", "http://www.ncbi.nlm.nih.gov/pubmed/7604973", "http://www.ncbi.nlm.nih.gov/pubmed/8917679", "http://www.ncbi.nlm.nih.gov/pubmed/14646509", "http://www.ncbi.nlm.nih.gov/pubmed/15382149", "http://www.ncbi.nlm.nih.gov/pubmed/10412642", "http://www.ncbi.nlm.nih.gov/pubmed/24562547", "http://www.ncbi.nlm.nih.gov/pubmed/16088381", "http://www.ncbi.nlm.nih.gov/pubmed/24481916", "http://www.ncbi.nlm.nih.gov/pubmed/9729489", "http://www.ncbi.nlm.nih.gov/pubmed/18432928", "http://www.ncbi.nlm.nih.gov/pubmed/12395931", "http://www.ncbi.nlm.nih.gov/pubmed/9648109", "http://www.ncbi.nlm.nih.gov/pubmed/23844597", "http://www.ncbi.nlm.nih.gov/pubmed/12405700", "http://www.ncbi.nlm.nih.gov/pubmed/18447956", "http://www.ncbi.nlm.nih.gov/pubmed/12642103", "http://www.ncbi.nlm.nih.gov/pubmed/8536072", "http://www.ncbi.nlm.nih.gov/pubmed/9196252", "http://www.ncbi.nlm.nih.gov/pubmed/16646085", "http://www.ncbi.nlm.nih.gov/pubmed/11525920", "http://www.ncbi.nlm.nih.gov/pubmed/24624212", "http://www.ncbi.nlm.nih.gov/pubmed/22876965" ], "ideal_answer": [ "The biochemical hallmark of apoptosis is internucleosomal DNA cleavage into oligonucleosome-length fragments. Measurement of apoptosis-associated internucleosomal DNA fragmentation through determination of the percentage of fragmented DNA by electrophoresis or centrifugation of whole cell lysates is by far the most common means of quantifying apoptosis. DNA fragmentation due to apoptosis can also be identified using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragments (TUNEL), in situ end labeling (ISEL) of the genomic DNA in fragmented nuclei, and measurement of cytosolic histone-bound DNA fragments (cell death ELISA assays)." ], "exact_answer": [ [ "electrophoresis of whole cell lysates" ], [ "centrifugation of whole cell lysates" ], [ "terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragments (TUNEL)" ], [ "in situ end labeling (ISEL) of the genomic DNA in fragmented nuclei" ], [ "measurement of cytosolic histone-bound DNA fragments (cell death ELISA assays)" ], [ "comet assay" ], [ "DAPI staining assay" ], [ "anti-DNA immunoelectron microscopy" ], [ "fluorescence correlation spectroscopy (FCS)" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0012501", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006915", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006309" ], "type": "list", "id": "553f96191d53b76422000004", "snippets": [ { "offsetInBeginSection": 442, "offsetInEndSection": 551, "text": "the biochemical hallmark of apoptosis is internucleosomal DNA cleavage into oligonucleosome-length fragments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9648109", "endSection": "abstract" }, { "offsetInBeginSection": 1377, "offsetInEndSection": 1522, "text": " terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragments (TUNEL) and in situ end labeling (ISEL) techniques", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9648109", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1559, "text": "TUNEL labeling of DNA fragments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9729489", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1058, "text": "Apoptotic cells in the specimens were quantitated after terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin-deoxyuridine triphosphate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9196252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The outcome of chronic ethanol consumption recorded in liver by in situ staining of the genomic DNA in fragmented nuclei indicates the course of cellular events that has been coined as apoptosis or programmed cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10069565", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 900, "text": " levels of cytosolic histone-bound DNA fragments (cell death ELISA assays)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8917679", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 362, "text": "Measurement of apoptosis-associated internucleosomal DNA fragmentation through determination of the percentage of fragmented DNA by electrophoresis or centrifugation of whole cell lysates is by far the most common means of quantifying apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1657218", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1146, "text": "Treatment with silica resulted in morphological changes typical of apoptotic cells, enhanced DNA fragmentation (a characteristic feature of programmed cell death), and significant alveolar macrophage apoptosis as observed by cell death ELISA assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8917679", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1384, "text": "Programmed cell death and DNA fragmentation were detected by Nile blue staining and cytochemical labeling of DNA fragmentation, respectively, in the interdigital mesoderm and in the regions of presumptive joints of the digit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7604973", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1151, "text": "Treatment with silica resulted in morphological changes typical of apoptotic cells, enhanced DNA fragmentation (a characteristic feature of programmed cell death), and significant alveolar macrophage apoptosis as observed by cell death ELISA assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8917679", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 901, "text": "Cell were treated with these particulates in vitro for 6 and 24 hr and examined for apoptosis by morphological analysis, DNA fragmentation, and levels of cytosolic histone-bound DNA fragments (cell death ELISA assays).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8917679", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 667, "text": "Featured in this unit is the TUNEL method of detecting cells that exhibit DNA fragmentation, which can also be performed on tissue sections to locate apoptotic cells in situ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18265108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Single-cell gel electrophoresis, or the comet assay, a technique widely used for DNA damage analysis, has been used recently for detecting DNA fragmentation in cells undergoing apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15382149", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1393, "text": "Programmed cell death and DNA fragmentation were detected by Nile blue staining and cytochemical labeling of DNA fragmentation, respectively, in the interdigital mesoderm and in the regions of presumptive joints of the digit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7604973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Single-cell gel electrophoresis assay monitors precise kinetics of DNA fragmentation induced during programmed cell death.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15382149", "endSection": "title" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1418, "text": "In addition, flow cytometry and DNA fragmentation assays confirmed DAPI staining assay results and indicated the occurrence of a programmed cell death (apoptosis) in the treated cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23844597", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 1084, "text": "Four frequently used flow cytometric techniques were evaluated: (i) Annexin V/Propidium Iodide assay, detecting the translocation of phosphatidylserine to the outer leaflet of the plasma membrane, simultaneously with preservation of the membrane integrity; (ii) Terminal deoxynucleotidyl Transferase (TdT) Uridine triphosphate (UTP) nick end labelling (TUNEL), revealing the presence of DNA strand breaks; (iii) DNA-flow cytometry, measuring DNA-stainability (DNA-fragmentation assay) and (iv) Phycoerythrin-labelled (PE) Apo2.7-assay, a monoclonal antibody against 7A6 antigen, a protein, which becomes exposed upon the mitochondrial membrane during apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14646509", "endSection": "abstract" }, { "offsetInBeginSection": 1985, "offsetInEndSection": 2152, "text": "The present single-cell gel electrophoresis assay offers a significant improvement in monitoring the kinetics of DNA fragmentation induced during programmed cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15382149", "endSection": "abstract" } ] }, { "body": "Does triiodothyronine stimulate red blood cell sodium potassium pump?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1333560", "http://www.ncbi.nlm.nih.gov/pubmed/2987290", "http://www.ncbi.nlm.nih.gov/pubmed/9781620" ], "ideal_answer": [ "An inverse correlation between this enzymatic action and free triiodothyronine (FT3) levels.\nThe effect of triiodothyronine (T3) on Na+,K(+)-ATPase activity in red blood cells may be different in vivo and in vitro." ], "exact_answer": "no", "type": "yesno", "id": "517a8a718ed59a060a00003e", "snippets": [ { "offsetInBeginSection": 75, "offsetInEndSection": 262, "text": "reduction in Na+,K+ATPase activity has been demonstrated in red blood cells (RBCs), as well as an inverse correlation between this enzymatic action and free triiodothyronine (FT3) levels.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9781620", "endSection": "sections.0" }, { "offsetInBeginSection": 263, "offsetInEndSection": 375, "text": "The restoration of normal FT3 values also brings about a normalization of Na+,K+ATPase activity in erythrocytes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9781620", "endSection": "sections.0" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1715, "text": "at hyperthyroid patients have decreased red cell Na/K-ATPase activity and provide direct evidence that erythrocyte ATPase activity is increased in hypothyroid patients. The change in enzyme activity in patients with nonthyroidal illness and decreased circulating T3 levels was comparable to that in hypothyroidism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2987290", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The effect of triiodothyronine (T3) on Na+,K(+)-ATPase activity of K562 human erythroleukemic cell was studied to understand why the erythrocyte sodium pump activity is decreased in hyperthyroidism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1333560", "endSection": "sections.0" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1100, "text": "We conclude that T3 stimulates Na+,K(+)-ATPase activity of K562 cells and in the presence of T3 during differentiation, the enzyme activity remains high.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1333560", "endSection": "sections.0" } ] }, { 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"http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C0795889", "o": "http://linkedlifedata.com/resource/umls/relation/R60648119" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R60545975", "o": "http://linkedlifedata.com/resource/umls/id/C0795889" }, { "p": "http://linkedlifedata.com/resource/umls/relatedConcept", "s": "http://linkedlifedata.com/resource/umls/relation/R60632992", "o": "http://linkedlifedata.com/resource/umls/id/C0795889" }, { "p": "http://linkedlifedata.com/resource/umls/relation", "s": "http://linkedlifedata.com/resource/umls/id/C0795889", "o": "http://linkedlifedata.com/resource/umls/relation/R60560915" } ], "ideal_answer": [ "Thyroid hormone concentrations are altered in patients with the Allan-Herndon-Dudley syndrome. In particular, high serum T3 levels and low-normal to low T4 serum levels are common in the Allan-Herndon-Dudley syndrome. It is, an X linked condition, is characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia in combination." ], "exact_answer": [ "Thyroid" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050631", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006728" ], "type": "factoid", "id": "530f900ee3eabad021000003", "snippets": [ { "offsetInBeginSection": 144, "offsetInEndSection": 313, "text": "This syndrome is characterized by axial hypotonia, severe mental retardation, dysarthria, athetoid movements, spastic paraplegia, and a typical thyroid hormone profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268987", "endSection": "abstract" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1445, "text": "Our case and the review of the pertinent literature suggest that Allan-Herndon-Dudley syndrome should be suspected in males with the typical neurological and thyroid profile, even in cases with normal brain myelination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268987", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Allan-Herndon-Dudley Syndrome (AHDS), an X linked condition, is characterized by congenital hypotonia that progresses to spasticity with severe psychomotor delays, in combination with altered thyroid hormone levels, in particular, high serum T3 levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170966", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 243, "text": "Mutations in the MCT8 gene are associated with Allan-Herndon-Dudley Syndrome (AHDS), consisting of severe psychomotor retardation and disturbed TH parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23550058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Allan-Herndon-Dudley syndrome (AHDS), an X linked condition, is characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia in combination with altered TH levels, in particular, high serum T3 levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419639", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 760, "text": "In two generations its presence was detected in the hemizygous state in two males with neurological abnormalities including mental retardation, axial hypotonia, hypertonia of arms and legs and athetoid movements. One of them presented normal thyroid hormone levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419639", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1318, "text": "Our results show the difficulty of distinguishing AHDS from patients with X-linked intellectual disability solely on the basis of clinical features and biochemical tests, and we advise screening for MCT8 mutations in either young or older patients with severe intellectual disability, axial hypotonia/dystonia, poor head control, spastic paraplegia, and athetoid movements even when they have normal thyroid hormone profiles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419639", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 642, "text": "Hemizygous MCT8 mutations in males cause severe psychomotor retardation, known as the Allan-Herndon-Dudley syndrome (AHDS), and abnormal serum TH levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23392090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor retardation characterized by neurological impairment and abnormal thyroid hormone (TH) levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161551", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 397, "text": "The hallmarks of Allan-Herndon-Dudley syndrome, caused by MCT8 mutations, are severe psychomotor retardation and elevated T(3) levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22719050", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 481, "text": "Inactivating mutations in the gene encoding MCT8 are associated with a severe form of psychomotor retardation and abnormal serum TH levels (Allan-Herndon-Dudley syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22543196", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 344, "text": "Mutations of this transporter determine a distinct X-linked psychomotor retardation syndrome (Allan-Herndon-Dudley syndrome (AHDS)) that is attributed to disturbed thyroid hormone levels, especially elevated T(3) levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896621", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 404, "text": "This syndrome is characterized by abnormally high T3, low/normal T4 serum levels and slightly elevated serum TSH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835051", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 959, "text": "High D1 activity in liver and kidney increases T4 and rT3 deiodination, and contributes to the increased serum T3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21825978", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 274, "text": "One of these, monocarboxylate transporter 8 (MCT8) is mutated in Allan-Herndon-Dudley syndrome, a severe mental retardation associated with abnormal thyroid hormone constellations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21264952", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 1037, "text": "The endocrine phenotype showed low serum total and free thyroxine (T4), very elevated total and free triiodothyronine (T3) and normal thyrotropin (TSH) with blunted response to thyrotropin-releasing hormone (TRH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20713192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Monocarboxylate transporter 8 (MCT8, SLC16A2) is a thyroid hormone (TH) transmembrane transport protein mutated in Allan-Herndon-Dudley syndrome, a severe X-linked psychomotor retardation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20628049", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 598, "text": "The clinical importance of TH transporters is dramatically shown in patients with mutations in MCT8, suffering from severe X-linked psychomotor retardation in combination with disturbed TH levels, especially high serum T(3) levels, now referred as Allan-Herndon-Dudley Syndrome (AHDS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20083155", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1145, "text": "Therefore, the criterion for MCT8 mutation screening in these patients is the profile of increased T(3) and low-normal to low FT(4) serum levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20083155", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 432, "text": "However, T3 level was elevated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19936787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "AIM: Mutations in the SLC16A2 gene have been implicated in Allan-Herndon-Dudley syndrome (AHDS), an X-linked learning disability* syndrome associated with thyroid function test (TFT) abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811520", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1120, "text": "Dystonic cerebral palsy was the most common initial clinical diagnosis, and AHDS was suspected only retrospectively, considering the characteristically abnormal thyroid function tests, with high serum tri-iodothyronine (T(3)), as the most consistent finding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811520", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1688, "text": "Although dysmorphic features suggestive of AHDS are not always present, T(3) measurement is a reliable screening test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811520", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 359, "text": "Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan-Herndon-Dudley syndrome, an X-linked mental retardation in which the patients also present with abnormally high 3',3,5-triiodothyronine (T(3)) plasma levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19641107", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 1011, "text": "With the discovery of monocarboxylate transporter 8 (MCT8) as a specific thyroid hormone transporter and the finding that mutations in this transporter lead to a syndrome of severe psychomotor retardation and elevated serum 3,3',5-tri-iodothyronine levels known as the Allan-Herndon-Dudley syndrome, the interest in this area of research has greatly increased. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19541799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Elevated serum triiodothyronine and intellectual and motor disability with paroxysmal dyskinesia caused by a monocarboxylate transporter 8 gene mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19018842", "endSection": "title" }, { "offsetInBeginSection": 509, "offsetInEndSection": 643, "text": "Additionally, the patient has a lesion in the left putamen region revealed by magnetic resonance imaging and elevated serum T3 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19018842", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1136, "text": "The identified MCT8 gene mutation (R271H) is very likely to be the genetic cause for neuronal hypothyroidism despite elevated serum T3 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19018842", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 545, "text": "Abnormal transport function is reflected by elevated free T3 and decreased free T4 levels along with clinical features characterized by neurological abnormalities including global developmental delay, central hypotonia, rotatory nystagmus, impaired hearing, spasticity and contractures of joints. We report a child with classical clinical features along with confirmatory deranged thyroid levels in blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18589880", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 609, "text": "Consistent with previous reports on MCT8 missense changes, the patient with c.1673G>A showed elevated serum T3 level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18398436", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1133, "text": "Moreover, we characterized a de novo translocation t(X;9)(q13.2;p24) in a female patient with full blown AHDS clinical features including elevated serum T3 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18398436", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1636, "text": "Taken together, these data indicate that MCT8 mutations are not common in non-AHDS MR patients yet they support that elevated serum T3 levels can be indicative for AHDS and that AHDS clinical features can be present in female MCT8 mutation carriers whenever there is unfavorable nonrandom X-inactivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18398436", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 890, "text": "Endocrine functions other than thyroid hormone regulation and metabolism were intact, resulting in normal hypothalamic/pituitary function tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17899191", "endSection": "abstract" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1222, "text": "Conclusion: the characteristic thyroid hormone function tests and brain MRI findings may allow screening of high-risk populations for a better understanding of MCT8 pathophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17899191", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 842, "text": "Importantly, these patients have elevated serum levels of free T(3), low to below normal serum levels of free T(4), and levels of thyroid stimulating hormone that are within the normal range.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574010", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 752, "text": "Pathogenic mutations in the MCT8 gene, which encodes a thyroid hormone transporter, results in elevated serum triiodothyronine (T3) levels, which were confirmed in four affected males of this family, while normal levels were found among obligate carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15980113", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1175, "text": "In addition, the severe muscle hypoplasia observed in most AHDS patients may be a consequence of high serum T3 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15980113", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 663, "text": "Abnormal transporter function is reflected in elevated free triiodothyronine and lowered free thyroxine levels in the blood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15889350", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 378, "text": "Mct8 transports thyroid hormones (T4 and T3), and the Allan-Herndon-Dudley syndrome is likely caused by lack of T3 transport to neurons during critical periods of fetal brain development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303950", "endSection": "abstract" } ] }, { "body": "Is selumetinib effective in thyroid cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23435040", "http://www.ncbi.nlm.nih.gov/pubmed/25268371", "http://www.ncbi.nlm.nih.gov/pubmed/25240824", "http://www.ncbi.nlm.nih.gov/pubmed/22451620", "http://www.ncbi.nlm.nih.gov/pubmed/25294906", "http://www.ncbi.nlm.nih.gov/pubmed/23406027", "http://www.ncbi.nlm.nih.gov/pubmed/24716986", "http://www.ncbi.nlm.nih.gov/pubmed/25309778" ], "ideal_answer": [ "Yes, selumetinib was shown to be effective treatment for thyroid cancer. Selumetinib may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer. Clinical efficacy of selumetinib was also investigated in other solid tumors." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3963", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013964", "http://www.disease-ontology.org/api/metadata/DOID:1781" ], "type": "yesno", "id": "56c1f00aef6e39474100003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268371", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: We completed a phase I clinical trial to test the safety and toxicity of combined treatment with cixutumumab (anti-IGF-1R antibody) and selumetinib (MEK 1/2 inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268371", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1272, "text": "Two patients achieved a partial response (one unconfirmed), including a patient with BRAF wild-type thyroid carcinoma, and a patient with squamous cell carcinoma of the tongue, and six patients achieved time to progression of>6 months, including patients with thyroid carcinoma, colorectal carcinoma, and basal cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268371", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1649, "text": "CONCLUSIONS: Our study of anti-IGF-1R antibody cixutumumab and MEK 1/2 inhibitor selumetinib showed that the combination is safe and well-tolerated at these doses, with preliminary evidence of clinical benefit and pharmacodynamic evidence of target inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25268371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "MHC class I loss is a frequent mechanism of immune escape in papillary thyroid cancer that is reversed by interferon and selumetinib treatment in vitro.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294906", "endSection": "title" }, { "offsetInBeginSection": 1469, "offsetInEndSection": 1592, "text": "Increased antigenicity following selumetinib and IFN treatment warrants further study for immunotherapy of progressive PTC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294906", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1032, "text": "The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25240824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "BACKGROUND AND AIM: Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24716986", "endSection": "abstract" }, { "offsetInBeginSection": 1561, "offsetInEndSection": 1834, "text": "CONCLUSIONS: Compared with current chemotherapy, selumetinib has modest clinical activity as monotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patients with BRAF or KRAS mutations hold great promise for cancer treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24716986", "endSection": "abstract" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1628, "text": "Selumetinib may be an effective redifferentiating agent and could be used within several years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406027", "endSection": "title" }, { "offsetInBeginSection": 345, "offsetInEndSection": 562, "text": "METHODS: We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406027", "endSection": "abstract" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1373, "text": "Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406027", "endSection": "abstract" }, { "offsetInBeginSection": 1934, "offsetInEndSection": 2182, "text": "CONCLUSIONS: Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406027", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 518, "text": "ECENT FINDINGS: For patients with advanced differentiated thyroid cancers, sorafenib, selumetinib, pazopanib and sunitinib have been investigated with promising results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23435040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24716986", "endSection": "abstract" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1711, "text": "Selumetinib may be an effective redifferentiating agent and could be used within several years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309778", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 611, "text": "Here, selumetinib targets the mitogen-activated protein kinase pathway in papillary thyroid carcinoma and shows limited single-agent activity in the patients with tumors that harbor the (V600E)BRAF mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22451620", "endSection": "abstract" }, { "offsetInBeginSection": 1937, "offsetInEndSection": 2185, "text": "CONCLUSIONS: Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406027", "endSection": "abstract" } ] }, { "body": "Where in the cell does the proteins S100A4 and p53 interact ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20591429", "http://www.ncbi.nlm.nih.gov/pubmed/16360031", "http://www.ncbi.nlm.nih.gov/pubmed/17504119", "http://www.ncbi.nlm.nih.gov/pubmed/23752197", "http://www.ncbi.nlm.nih.gov/pubmed/17497677", "http://www.ncbi.nlm.nih.gov/pubmed/11278647", "http://www.ncbi.nlm.nih.gov/pubmed/20191297", "http://www.ncbi.nlm.nih.gov/pubmed/11836260", "http://www.ncbi.nlm.nih.gov/pubmed/15116098", "http://www.ncbi.nlm.nih.gov/pubmed/20177948", "http://www.ncbi.nlm.nih.gov/pubmed/11527429", "http://www.ncbi.nlm.nih.gov/pubmed/19819244", "http://www.ncbi.nlm.nih.gov/pubmed/12942774", "http://www.ncbi.nlm.nih.gov/pubmed/20140014" ], "triples": [ { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/S100A4+protein%2C+human", "o": "142662-27-9" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/S100A4+protein%2C+human", "o": "S100A4 protein, human" } ], "ideal_answer": [ "S100A4 interacts with p53 in the cell nucleus." ], "exact_answer": [ "nucleus" ], "concepts": [ "http://www.uniprot.org/uniprot/S10A4_HUMAN", "http://www.uniprot.org/uniprot/S10A4_BOVIN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002039", "http://www.uniprot.org/uniprot/P53_MACFU", "http://www.uniprot.org/uniprot/P53_CANFA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016158", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016159", "http://www.uniprot.org/uniprot/S10A4_RAT", "http://www.uniprot.org/uniprot/PER53_ARATH" ], "type": "factoid", "id": "54e8c7220fc566b149000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "S100A4 interacts with p53 in the nucleus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23752197", "endSection": "title" }, { "offsetInBeginSection": 395, "offsetInEndSection": 461, "text": "we show that endogenous S100A4 and p53 interact in complex samples", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23752197", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 668, "text": "using proximity ligation assay, we show that the interaction takes place in the cell nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23752197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Coexpression and nuclear colocalization of metastasis-promoting protein S100A4 and p53 without mutual regulation in colorectal carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20191297", "endSection": "title" } ] }, { "body": "What are the applications of a Dermaroller ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23960389", "http://www.ncbi.nlm.nih.gov/pubmed/20808602", "http://www.ncbi.nlm.nih.gov/pubmed/20300368" ], "ideal_answer": [ "Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.\nMicroneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy.", "Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy.", "Microneedling therapy seems to be a simple and effective treatment option for the management of atrophic facial scars. Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery. Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy. " ], "type": "summary", "id": "5325a1a69b2d7acc7e000025", "snippets": [ { "offsetInBeginSection": 1819, "offsetInEndSection": 2148, "text": "Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23960389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20808602", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1632, "text": "Microneedling therapy seems to be a simple and effective treatment option for the management of atrophic facial scars.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20300368", "endSection": "abstract" } ] }, { "body": "Are immune cells affected in Amyotrophic Lateral Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17852013", "http://www.ncbi.nlm.nih.gov/pubmed/7595631", "http://www.ncbi.nlm.nih.gov/pubmed/23881705", "http://www.ncbi.nlm.nih.gov/pubmed/21829620", "http://www.ncbi.nlm.nih.gov/pubmed/25199710", "http://www.ncbi.nlm.nih.gov/pubmed/7551976", "http://www.ncbi.nlm.nih.gov/pubmed/25904790", "http://www.ncbi.nlm.nih.gov/pubmed/20406178", "http://www.ncbi.nlm.nih.gov/pubmed/24995608" ], "ideal_answer": [ "In ALS T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it.", "The intrathymic injection of donor spleen cells into antilymphocyte serum (ALS)-treated mice induces significant prolongation of donor skin grafts. To elucidate possible mechanisms involved in the induction of unresponsiveness in ALS-treated mice after intrathymic injection of donor spleen cells, we have analysed the reactivity of lymphoid cells from unresponsive mice in various ways. Here, we show that in the mutant superoxide dismutase 1 G93A (mSOD1) mouse model of ALS, the levels of natural killer T (NKT) cells increased dramatically, and T-cell distribution was altered both in lymphoid organs and in the spinal cord relative to wild-type mice. Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma.", "Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012598", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000690", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477", "http://www.disease-ontology.org/api/metadata/DOID:230" ], "type": "yesno", "id": "56cae51f5795f9a73e000025", "snippets": [ { "offsetInBeginSection": 787, "offsetInEndSection": 1125, "text": "Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25904790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Immunization with a Myelin-Derived Antigen Activates the Brain's Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25904790", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Amyotrophic lateral sclerosis (ALS) is a rapidly progressing fatal neurodegenerative disorder characterized by the selective death of motor neurons (MN) in the spinal cord, and is associated with local neuroinflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21829620", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 486, "text": "T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21829620", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 1022, "text": "As disease accelerates, a shift occurs from beneficial immune responses (involving M2 microglia and regulatory T-cells) to deleterious immune responses (involving M1 microglia and Th1 cells). In this review, we underscore the importance of immune-mediated mechanisms in the pathogenesis of ALS and discuss the alterations and distinct phenotypes of immune cells at the different stages of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23881705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": " Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "The immune system has been found to be involved with positive and negative effects in the nervous system of amyotrophic lateral sclerosis (ALS) patients. In general, T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20406178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852013", "endSection": "abstract" }, { "offsetInBeginSection": 2147, "offsetInEndSection": 2458, "text": "We propose the following mechanism for the effect of mesenchymal stem cells (MSCs) administered intrathecally in amyotrophic lateral sclerosis (ALS): MSCs increase infiltration of peripheral immune cells into CNS and skew the infiltrated immune cells toward regulatory T lymphocytes (Treg ) and Th2 lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Immune cell infiltration to the brain's territory was considered for decades to reflect a pathological process in which immune cells attack the central nervous system (CNS); such a process is observed in the inflammatory autoimmune disease, multiple sclerosis (MS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25199710", "endSection": "abstract" } ] }, { "body": "Are OATP1B1 and OATP1B3 associated with bilirubin transport?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24523126", "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "http://www.ncbi.nlm.nih.gov/pubmed/23695864", "http://www.ncbi.nlm.nih.gov/pubmed/15535988", "http://www.ncbi.nlm.nih.gov/pubmed/24459177", "http://www.ncbi.nlm.nih.gov/pubmed/24151358", "http://www.ncbi.nlm.nih.gov/pubmed/21395542", "http://www.ncbi.nlm.nih.gov/pubmed/25204339", "http://www.ncbi.nlm.nih.gov/pubmed/17973861", "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "http://www.ncbi.nlm.nih.gov/pubmed/18509604", "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "http://www.ncbi.nlm.nih.gov/pubmed/23886114" ], "ideal_answer": [ "Yes, OATP1B1 and OATP1B3 are involved in the transport of bilirubin." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001663", "http://amigo.geneontology.org/amigo/term/GO:0015723", "http://www.biosemantics.org/jochem#4274830" ], "type": "yesno", "id": "571e3e2abb137a4b0c000008", "snippets": [ { "offsetInBeginSection": 621, "offsetInEndSection": 811, "text": "OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886114", "endSection": "abstract" }, { "offsetInBeginSection": 1906, "offsetInEndSection": 2193, "text": "Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523126", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1768, "text": "Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 992, "text": "OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886114", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 919, "text": "However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 1864, "offsetInEndSection": 2104, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 360, "text": "Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "title" }, { "offsetInBeginSection": 1775, "offsetInEndSection": 1927, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1516, "text": "The data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood, from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and OATP1B3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24151358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyperbilirubinemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "title" }, { "offsetInBeginSection": 621, "offsetInEndSection": 809, "text": "OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886114", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 222, "text": "Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1429, "text": "Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 1630, "offsetInEndSection": 1916, "text": "Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523126", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 736, "text": "In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 \u00b5M), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 \u00b5M), OATP1B3 (IC50 0.18 \u00b5M), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 \u00b5M), which transport bilirubin and its conjugates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25204339", "endSection": "abstract" }, { "offsetInBeginSection": 1632, "offsetInEndSection": 1783, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1872, "text": "Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "OATP1B1 (a.k.a. OATP-C, OATP2, LST-1, or SLC21A6) is a liver-specific organic anion uptake transporter and has been shown to be a higher affinity bilirubin uptake transporter than OATP1B3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15535988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886114", "endSection": "title" }, { "offsetInBeginSection": 1630, "offsetInEndSection": 1948, "text": "Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh. Adv Pharmacol 63:1-42, 2012). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523126", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1196, "text": "Using mice deficient in Oatp1a/1b and in the multispecific sinusoidal export pump Abcc3, we found that Abcc3 secretes bilirubin conjugates into the blood, while Oatp1a/1b transporters mediate their hepatic reuptake. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232210", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 224, "text": "Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17973861", "endSection": "title" }, { "offsetInBeginSection": 119, "offsetInEndSection": 272, "text": "Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17973861", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 1085, "text": "However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia. Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 1431, "text": "Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase. Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23750830", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 738, "text": "In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 \u00b5M), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 \u00b5M), OATP1B3 (IC50 0.18 \u00b5M), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 \u00b5M), which transport bilirubin and its conjugates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25204339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886114", "endSection": "title" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1231, "text": "3.\u2002\u2009The results indicated that in vivo Fi values >0.2 or R-values >1.5 for OATP1B1 or OATP1B3, but not UGT1A1, are associated with previously reported clinical cases of drug-induced unconjugated hyperbilirubinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886114", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 811, "text": "OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23886114", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of eprotirome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22784847", "http://www.ncbi.nlm.nih.gov/pubmed/22542282", "http://www.ncbi.nlm.nih.gov/pubmed/24440706", "http://www.ncbi.nlm.nih.gov/pubmed/23776891", "http://www.ncbi.nlm.nih.gov/pubmed/23565368", "http://www.ncbi.nlm.nih.gov/pubmed/20872316", "http://www.ncbi.nlm.nih.gov/pubmed/20935564", "http://www.ncbi.nlm.nih.gov/pubmed/24731671", "http://www.ncbi.nlm.nih.gov/pubmed/25172631", "http://www.ncbi.nlm.nih.gov/pubmed/20220185", "http://www.ncbi.nlm.nih.gov/pubmed/20625286", "http://www.ncbi.nlm.nih.gov/pubmed/18447589" ], "ideal_answer": [ "Eprotirome belongs to thyromimetics and has selective TR\u03b21 activity. It has shown to be effective in dyslipidemia by the lipid-lowering action of TH in the liver and also in obesity." ], "type": "summary", "id": "54f1e4d0c409818c32000002", "snippets": [ { "offsetInBeginSection": 456, "offsetInEndSection": 537, "text": "Eprotirome and Sobetirome are 2 thyromimetics that have selective TR\u03b21 activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565368", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1355, "text": "Recently, the development of the most promising agent in this class, eprotirome, was halted over toxicology concerns following long-term canine studies. Consequently, the future of contemporary TR\u03b2 agonists is unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22784847", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 348, "text": "We designed novel thyromimetics with high receptor (TR\u03b2) and organ (liver) selectivity based on the structure of eprotirome (3) and molecular modeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22542282", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1163, "text": "In humans, eprotirome exerts favorable lipid-modulating effects while lacking thyroid hormone-related side-effects and maintaining normal hypothalamic-pituitary-thyroid feedback.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20935564", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 658, "text": "This review details recent advances in the development of TR\u03b2 subtype- and liver-selective STRM analogs, and presents the results of preliminary clinical trials with one of these compounds, eprotirome (KB-2115; Karo Bio AB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20872316", "endSection": "abstract" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1564, "text": "Examples of synthetic analogues are GC-1 (or sobetirome) and KB2115 (or eprotirome) which show ipolipidaemic and antiaterogenic capacities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625286", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 555, "text": "METHODS: The history of thyromimetics in atherosclerosis and dyslipidaemia is reviewed as the background to the recent publication of the first human data on a new selective thyromimetic, KB-2115 (eprotirome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18447589", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 532, "text": " Eprotirome and Sobetirome are 2 thyromimetics that have selective TR\u03b21 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565368", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 535, "text": "Eprotirome and Sobetirome are 2 thyromimetics that have selective TR\u03b21 activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23565368", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 976, "text": "We also examined the effects of the TR\u03b2 agonist eprotirome on hepatic gene regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24440706", "endSection": "abstract" } ] }, { "body": "What is the role of music therapy in coma patients.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7513085", "http://www.ncbi.nlm.nih.gov/pubmed/12046234", "http://www.ncbi.nlm.nih.gov/pubmed/25071434", "http://www.ncbi.nlm.nih.gov/pubmed/25287735", "http://www.ncbi.nlm.nih.gov/pubmed/20663643", "http://www.ncbi.nlm.nih.gov/pubmed/23816631" ], "ideal_answer": [ "Several studies have shown that music can boost cognitive functions in patients with a disorder of consciousness but it is difficult to conclude since they did not use quantified measures and a control condition/group. Active improvised music therapy may offer an adjuvant form of treatment in the early rehabilitation of severe brain-injured patients." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009147", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003128" ], "type": "summary", "id": "56bf5b0cef6e394741000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "[Beneficial effect of preferred music on cognitive functions in minimally conscious state patients].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287735", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Several studies have shown that music can boost cognitive functions in normal and brain-damaged subjects. A few studies have suggested a beneficial effect of music in patients with a disorder of consciousness but it is difficult to conclude since they did not use quantified measures and a control condition/group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287735", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1082, "text": ". This new protocol suggests that preferred music has a beneficial effect on the cognitive abilities of MCS patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "This review presents an overview of the use of music therapy in neurological early rehabilitation of patients with coma and other disorders of consciousness (DOC) such as unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071434", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 789, "text": "The programs' content consisted of recreation and communication options, which involved activating music, videos, and basic requests, sending and receiving (listening to) text messages, and placing phone calls. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23816631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Active music therapy in the rehabilitation of severe brain injured patients during coma recovery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12046234", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Active improvised music therapy may offer an adjuvant from of treatment in the early rehabilitation of severe brain-injured patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12046234", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 791, "text": "Our preliminary results show a significant improvement of the collaboration of the severe brain-injured patients and a reduction of undesired behaviours such as inertia (reduced psychomotor initiative) or psychomotor agitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12046234", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 654, "text": "Hence, it is possible for music therapy to both establish contact with the seemingly non-responsive patient and re-stimulate the person's fundamental communication competencies and experience at the emotional, social and cognitive levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7513085", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 549, "text": "Six studies focused on the provision of multisensory stimulation or music therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20663643", "endSection": "abstract" } ] }, { "body": "Which is the causative agent of malaria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12930149", "http://www.ncbi.nlm.nih.gov/pubmed/15003844", "http://www.ncbi.nlm.nih.gov/pubmed/15117937", "http://www.ncbi.nlm.nih.gov/pubmed/19184366", "http://www.ncbi.nlm.nih.gov/pubmed/20635416", "http://www.ncbi.nlm.nih.gov/pubmed/14556002", "http://www.ncbi.nlm.nih.gov/pubmed/19779742", "http://www.ncbi.nlm.nih.gov/pubmed/19666023", "http://www.ncbi.nlm.nih.gov/pubmed/21670272", "http://www.ncbi.nlm.nih.gov/pubmed/22819049", "http://www.ncbi.nlm.nih.gov/pubmed/11504465", "http://www.ncbi.nlm.nih.gov/pubmed/14638789", "http://www.ncbi.nlm.nih.gov/pubmed/22341220", "http://www.ncbi.nlm.nih.gov/pubmed/21206476", "http://www.ncbi.nlm.nih.gov/pubmed/12626578", "http://www.ncbi.nlm.nih.gov/pubmed/2067470", "http://www.ncbi.nlm.nih.gov/pubmed/23405174", "http://www.ncbi.nlm.nih.gov/pubmed/20078859", "http://www.ncbi.nlm.nih.gov/pubmed/15701514", "http://www.ncbi.nlm.nih.gov/pubmed/21297002", "http://www.ncbi.nlm.nih.gov/pubmed/10585859", "http://www.ncbi.nlm.nih.gov/pubmed/23246819", "http://www.ncbi.nlm.nih.gov/pubmed/22524128", 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Plasmodium gallinaceum is the main bird malaria causative agent and Plasmodium yoelli is the principle rodent malaria agent." ], "exact_answer": [ "Plasmodium species", "Plasmodium spp." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008288", "http://www.disease-ontology.org/api/metadata/DOID:12978", "http://www.disease-ontology.org/api/metadata/DOID:14067", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010965", "http://www.disease-ontology.org/api/metadata/DOID:12365", "http://www.disease-ontology.org/api/metadata/DOID:14324", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016778", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016780" ], "type": "factoid", "id": "517194ef8ed59a060a000011", "snippets": [ { "offsetInBeginSection": 13, "offsetInEndSection": 107, "text": "lasmodium falciparum the main causative agent of malaria is an important public health vector.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382752", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 109, "text": "Plasmodium falciparum the main causative agent of malaria is an important public health vector. <", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382752", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Overcoming antigenic variation is one of the major challenges in the development of an effective vaccine against Plasmodium falciparum, a causative agent of human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23293353", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "[The vivax malaria causative agent Plasmodium ovale: the present global area, intraspecies polymorphism, importation to the Russian Federation (1992-2011)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23088152", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The global area for Plasmodium ovale is small as compared with that for other species of human malaria pathogens.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23088152", "endSection": "sections.0" }, { "offsetInBeginSection": 109, "offsetInEndSection": 1148, "text": "Parasites that have been described to affect the central nervous system (CNS), either as the dominant or as a collateral feature, include cestodes (Taenia solium (neurocysticerciasis), Echinococcus granulosus (cerebral cystic echinococcosis), E. multilocularis (cerebral alveolar echinococcosis), Spirometra mansoni (neurosparganosis)), nematodes (Toxocara canis and T. cati (neurotoxocariasis), Trichinella spiralis (neurotrichinelliasis), Angiostrongylus cantonensis and A. costaricensis (neuroangiostrongyliasis), Gnathostoma spinigerum (gnathostomiasis)), trematodes (Schistosoma mansoni (cerebral bilharziosis), Paragonimus westermani (neuroparagonimiasis)), or protozoa (Toxoplasma gondii (neurotoxoplasmosis), Acanthamoeba spp. or Balamuthia mandrillaris (granulomatous amoebic encephalitis), Naegleria (primary amoebic meningo-encephalitis), Entamoeba histolytica (brain abscess), Plasmodium falciparum (cerebral malaria), Trypanosoma brucei gambiense/rhodesiense (sleeping sickness) or Trypanosoma cruzi (cerebral Chagas disease))", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046708", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Plasmodium falciparum is the causative agent of malaria, a deadly infectious disease for which treatments are scarce and drug-resistant parasites are now increasingly found.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819049", "endSection": "sections.0" }, { "offsetInBeginSection": 107, "offsetInEndSection": 320, "text": "In contrast, it has been thought that Plasmodium spp., the causative agent of malaria, rely mainly on cytosolic glycolysis but not mitochondrial oxidative phosphorylation for energy production during blood stages.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22628552", "endSection": "sections.0" }, { "offsetInBeginSection": 165, "offsetInEndSection": 447, "text": "Whereas no biological activity was previously identified for 1, the material derived from the efficient synthesis enabled additional bioactivity tests leading to the identification of a notable activity against insect cells and Plasmodium falciparum, the causative agent of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22563351", "endSection": "sections.0" }, { "offsetInBeginSection": 102, "offsetInEndSection": 283, "text": "Plasmodium falciparum, the causative agent of malaria, encodes an SSB protein that localizes to the apicoplast and likely functions in the replication and maintenance of its genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22543099", "endSection": "sections.0" }, { "offsetInBeginSection": 174, "offsetInEndSection": 411, "text": "While observing cells by time-lapse imaging is a standard procedure in many systems, this technique was until recently not available for blood stages of Plasmodium falciparum, the causative agent of the most severe form of human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22341220", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The causative agent of malaria, Plasmodium, possesses three translationally active compartments: the cytosol, the mitochondrion and a relic plastid called the apicoplast.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22222968", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 166, "text": "The merozoite surface protein (MSP)-1 of Plasmodium falciparum, the causative agent of malaria tropica, is considered to be a promising vaccine candidate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22095915", "endSection": "sections.0" }, { "offsetInBeginSection": 115, "offsetInEndSection": 255, "text": "The genus Plasmodium, the causative agent of malaria, has the smallest mt genome in the form of a tandemly repeated, linear element of 6 kb.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21329764", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "The culminating step of the intraerythrocytic development of Plasmodium falciparum, the causative agent of malaria, is the spectacular release of multiple invasive merozoites on rupture of the infected erythrocyte membrane.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297002", "endSection": "sections.0" }, { "offsetInBeginSection": 158, "offsetInEndSection": 322, "text": "Plasmodium falciparum, the causative agent of human malaria, lacks a conventional tricarboxylic acid cycle and depends exclusively on glycolysis for ATP production.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21209090", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702404", "endSection": "sections.0" }, { "offsetInBeginSection": 126, "offsetInEndSection": 325, "text": "The Hsp90 protein from the parasite Plasmodium falciparum, the causative agent of malaria, is critical for this organism's survival; the anti-Hsp90 drug geldanamycin is toxic to P. falciparum growth.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20635416", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "A novel family of 1H-imidazol-2-yl-pyrimidine-4,6-diamines has been identified with potent activity against the erythrocyte-stage of Plasmodium falciparum (Pf), the most common causative agent of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20610151", "endSection": "sections.0" }, { "offsetInBeginSection": 186, "offsetInEndSection": 326, "text": "The Plasmodium parasite, causative agent of malaria, infects RBC that are phagocytosed by DC and macrophages during the course of infection.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20500669", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Plasmodium falciparum is the causative agent of malaria, a disease where new drug targets are required due to increasing resistance to current anti-malarials.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20353400", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed as potential vaccine candidates.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19931645", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Few studies have investigated the pathophysiologic mechanisms responsible for what seems to be a possible interaction between Plasmodium falciparum, the causative agent of malaria, and HIV-1 in dually infected patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19801158", "endSection": "sections.0" }, { "offsetInBeginSection": 309, "offsetInEndSection": 456, "text": "We show that orthochromatic cells are the earliest stages that may be invaded by Plasmodium falciparum, the causative agent of fatal human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19706885", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Infection by Plasmodium, the causative agent of malaria, is associated with hemolysis and therefore with release of hemoglobin from RBC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19706490", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Plasmodium falciparum, the causative agent of malignant malaria, is among the most severe human infectious diseases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666593", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Plasmodium falciparum, the most important causative agent of human malaria, undergoes antigenic variation as a means of prolonging infection and ensuring transmission between hosts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666023", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "L-Malate dehydrogenase (PfMDH) from Plasmodium falciparum, the causative agent for the most severe form of malaria, has shown remarkable similarities to L: -lactate dehydrogenase (PfLDH).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19184366", "endSection": "sections.0" }, { "offsetInBeginSection": 138, "offsetInEndSection": 303, "text": "FQ is able to overcome the chloroquine (CQ) resistance problem, an important limit to the control of Plasmodium falciparum, the principal causative agent of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18563912", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The causative agent of malaria, Plasmodium falciparum posses a single aquaglyceroporin (PfAQP) which represents a potential drug target for treatment of the disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18295508", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "An essential requisite for transmission of Plasmodium, the causative agent of malaria, is the successful completion of a complex developmental cycle in its mosquito vector.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18248630", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "In Plasmodium falciparum, the causative agent of cerebral malaria, silent information regulator 2 (Sir2) has been implicated in pathogenesis through its role in var gene silencing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18221799", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Plasmodium falciparum, the causative agent of human malaria, is totally dependent on de novo pyrimidine biosynthetic pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18082626", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Plasmodium falciparum, the causative agent of the fatal form of malaria, synthesizes GMP primarily from IMP and, hence, needs active GMPS (GMP synthetase) for its survival.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868038", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Plasmodium falciparum is the causative agent of the most severe type of malaria, a life-threatening disease affecting the lives of over three billion people.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17822713", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 150, "text": "Plasmodium falciparum, the causative agent of the most serious form of malaria, infects about 5-10% of the world human population per year.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17024857", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Plasmodium vivax is an important human pathogen causing malaria in more temperate climates of the world. Similar to Plasmodium falciparum, the causative agent for malaria tropica, drug resistance is beginning to emerge for this parasite species and this hampers adequate treatment of infection.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16458301", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Malaria kills more than one million people a year, and understanding the historical association between its most notorious causative agent, Plasmodium falciparum, and its mosquito vectors is important in fighting the disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16222020", "endSection": "sections.0" }, { "offsetInBeginSection": 166, "offsetInEndSection": 347, "text": "We show here that macrophages are mandatory for NK cell IFN-gamma secretion in response to erythrocytes infected with Plasmodium falciparum (Pf), a causative agent of human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16203971", "endSection": "sections.0" }, { "offsetInBeginSection": 76, "offsetInEndSection": 167, "text": "Plasmodium falciparum is the causative agent of the most severe and mortal type of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15950069", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Plasmodium falciparum is the main causative agent of tropical malaria, the most severe parasitic disease in the world. Growing resistance of Plasmodia towards available drugs is an increasing problem in countries where malaria is endemic.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15878595", "endSection": "sections.0" }, { "offsetInBeginSection": 117, "offsetInEndSection": 234, "text": "The presence of antisense RNA in Plasmodium falciparum, the causative agent of severe malaria, remains controversial.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703443", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Plasmodium falciparum, the causative agent of malaria, is sensitive to oxidative stress and therefore the family of antioxidant enzymes, peroxiredoxins (Prxs) represent a target for antimalarial drug design.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701514", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "In the Republic of Yemen, Plasmodium falciparum is the predominant causative agent of malaria and is associated with adverse consequences for pregnant women and their babies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15339111", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Plasmodium falciparum, the causative agent of the most lethal form of human malaria, uses multiple ligand-receptor interactions to invade host red blood cells (RBCs).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265796", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Comparative genomic analysis of the malaria causative agent, Plasmodium falciparum, with other eukaryotes for which the complete genome is available, revealed that the genome from P. falciparum was more similar to the genome of a plant, Arabidopsis thaliana, than to other non-apicomplexan taxa.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15246528", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Plasmodium falciparum, the causative agent of the most lethal form of human malaria, totally depends on de novo pyrimidine biosynthetic pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15147974", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Plasmodium falciparum, the causative agent of malaria, relies extensively on glycolysis coupled with homolactic fermentation during its blood-borne stages for energy production.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15117937", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Plasmodium falciparum is the causative agent of the most severe form of human malaria. The rapid multiplication of the parasite within human erythrocytes requires an active production of new membranes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15073329", "endSection": "sections.0" }, { "offsetInBeginSection": 157, "offsetInEndSection": 401, "text": "Seven sPLA(2)s from groups IA, IB, IIA and III, were tested here in different culture conditions for inhibition of the in vitro intraerythrocytic development of Plasmodium falciparum, the causative agent of the most severe form of human malaria", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15033330", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Plasmodium falciparum, the causative agent of the most lethal form of human malaria, relies on de novo pyrimidine biosynthesis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15003844", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "In spite of research efforts to develop vaccines against the causative agent of human malaria, Plasmodium falciparum, effective control remains elusive.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14638789", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Plasmodium, the causative agent of malaria, has to undergo sexual differentiation and development in anopheline mosquitoes for transmission to occur.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14627712", "endSection": "sections.0" }, { "offsetInBeginSection": 117, "offsetInEndSection": 254, "text": "For Plasmodium falciparum, a causative agent of tropical malaria, TrxR is an essential protein which has been validated as a drug target.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14609342", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Plasmodium, the causative agent of malaria, must first infect hepatocytes to initiate a mammalian infection.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14556002", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Cyclin dependent protein kinases (CDKs) have become attractive drug targets in an effort to identify effective inhibitors of the parasite Plasmodium falciparum, the causative agent of the most severe form of human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12930149", "endSection": "sections.0" }, { "offsetInBeginSection": 190, "offsetInEndSection": 377, "text": "It is well established that protection against one such disease, malaria, requires strong CD8(+) T cell responses targeted against the liver stages of the causative agent, Plasmodium spp.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12626578", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "A novel method for the in vitro detection of the protozoan Plasmodium, the causative agent of malaria, has been developed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12139027", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Trypanosomes do not inhabit or grow in anopheles mosquitoes, the vector for the transmission of Plasmodium parasites the causative agent for malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125103", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The genome sequence of Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, rapidly approaches completion, but our ability to genetically manipulate this organism remains limited.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11796125", "endSection": "sections.0" }, { "offsetInBeginSection": 95, "offsetInEndSection": 229, "text": "It is caused by a number of species of the genus Plasmodium, and Plasmodium falciparum is the causative agent of the most lethal form.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11839179", "endSection": "sections.0" }, { "offsetInBeginSection": 181, "offsetInEndSection": 333, "text": "To complete its life cycle in the mosquito, Plasmodium, the causative agent of malaria, has to traverse the epithelia of the midgut and salivary glands.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11687659", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "In Plasmodium falciparum, the causative agent of human malaria, the catalytic subunit gene of cAMP-dependent protein kinase (Pfpka-c) exists as a single copy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11559352", "endSection": "sections.0" }, { "offsetInBeginSection": 189, "offsetInEndSection": 494, "text": "Sulfadoxine is the most extensively used drug of this group of drugs and is usually combined with pyrimethamine (Fansidar), particularly for the control of Plasmodium falciparum, the causative agent of the most lethal form of malaria. Resistance to the sulfadoxine/pyrimethamine combination is widespread.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11504465", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "A putative glutathione peroxidase gene (Swiss-Prot accession number Z 68200) of Plasmodium falciparum, the causative agent of tropical malaria, was expressed in Escherichia coli and purified to electrophoretic homogeneity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11087748", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Apical membrane antigen 1 (AMA1) is an asexual blood-stage protein expressed in the invasive merozoite form of Plasmodia species, which are the causative agent of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11115107", "endSection": "sections.0" }, { "offsetInBeginSection": 350, "offsetInEndSection": 571, "text": "In the case of Plasmodium falciparum, the causative agent of malaria tropica, this approach is especially interesting, because here both key enzymes, ODC and AdoMetDC, are combined in a bifunctional protein, ODC/AdoMetDC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11085920", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Plasmodium falciparum, the causative agent of the most lethal form of human malaria, is incapable of de novo purine synthesis, and thus, purine acquisition from the host is an indispensable nutritional requirement.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10744765", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "A laboratory model of circulation of the malaria causative agent P. gallinaceum has been used to show that the effect of precocene (antijuvenoid) leads to a statistically significant reduction in the proportion of infected females developing eggs after blood suction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10703207", "endSection": "sections.0" }, { "offsetInBeginSection": 447, "offsetInEndSection": 690, "text": "A cell-free incubation system prepared from asexual erythrocytic stages of Plasmodium falciparum, the causative agent of malaria in humans, is capable of synthesizing the same spectrum of GPIs as that found in metabolically labelled parasites.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10585859", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The Plasmodium falciparum malaria parasite is the causative agent of malaria tropica.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9927744", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The gene of an NADP+-specific glutamate dehydrogenase was cloned from Plasmodium falciparum, the causative agent of tropical malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9874251", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "This study describes the synergistic interaction of two calcium channel blockers, verapamil (VR) and SR33557 or fantofarone (SR), in reversing chloroquine resistance in Plasmodium falciparum, the causative agent of human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9514077", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Plasmodium falciparum is the major causative agent of malaria, a disease of worldwide importance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8816746", "endSection": "sections.0" }, { "offsetInBeginSection": 97, "offsetInEndSection": 422, "text": "Two enzymes were purified to homogeneity from the intraerythrocytic malarial parasite Plasmodium falciparum: glutathione disulfide reductase, an antioxidative enzyme, which appears to play an essential role for parasite growth and differentiation, and glutamate dehydrogenase, an enzyme not occurring in the host erythrocyte.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8631352", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The paper provides evidence that the An. sacharovi females which do not develop mature eggs after blood-sucking on the malaria-infected donor could not be infected by the bird malaria agent P. gallinaceum.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7715553", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Plasmodium falciparum is the causative agent of malaria tropica in man.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8300589", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Plastid origin of an extrachromosomal DNA molecule from Plasmodium, the causative agent of malaria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1474844", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "[New models of the circulation of the causative agent of malaria Plasmodium gallinaceum using malarial mosquitoes in the fauna of the USSR].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1813841", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "[Experimental research on the effect of biologically active substances on the susceptibility of mosquitoes to the causative agent of malaria. 3. Algae, fertilizers].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1648659", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 467, "text": "On a model pair Aedes aegypti--Plasmodium gallinaceum in has been shown that changes in the conditions of larvae development caused by the addition into the water medium of the live culture of Synochocystis sp. cyanobacteria or green seaweeds Chlorella vulgaris, acetone extracts from the live culture precipitate or Chlorella powder, as well as nitrogen-containing fertilizer--ammonium chloride did not lower the sensitivity of the imago flying to malaria parasites.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1648659", "endSection": "sections.0" }, { "offsetInBeginSection": 155, "offsetInEndSection": 479, "text": "The mechanism of chloroquine resistance has not been known but recent evidence from Plasmodium falciparum, the causative agent of the most severe form of human malaria, suggested similarities to the multidrug resistance phenotype (MDR) of mammalian tumour cells which is mediated by a protein molecule termed P-glycoprotein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15463447", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "The feasibility was determined of influencing Ae. aegypti sensitivity to bird malaria agent P. gallinaceum by sublethal concentrations of herbicides (ordram and propanide) and fungicides (fundozol and blue vitriol) introduced into the larvae habitation medium or into the imago feed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2067482", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "[An experimental study of the effect of different biologically active substances on the susceptibility of mosquitoes to the causative agent of malaria. 1. Insect development regulators].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2067470", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "It has been shown on the model pair Ae. aegypti-P. gallinaceum that dimilin, an inhibitor of insect chitin synthesis has practically no effect on female sensitivity to malaria agent.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2067470", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "[The absence of an action of the pyrethroids deltamethrin and cypermethrin on mosquito susceptibility to the causative agent of malaria].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2191201", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Mosquitos Ae. aegypti and An. stephensi contact with sublethal doses of deltametrin and cypermetrin pyretroids at larval stage and in grown state, when diet includes sugar with pyretroids, had no influence on the sensitivity of survived females to malaria agents P. gallinaceum and P. berghei.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2191201", "endSection": "sections.0" }, { "offsetInBeginSection": 114, "offsetInEndSection": 368, "text": "This prompted us to purify and characterize the topoisomerases I and II present in the erythrocytes of protozoan parasites of the genus Plasmodium, the causative agent of malaria, in order to later use these enzymatic systems in antimalarial drug assays.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3011062", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The problem of drug resistance of Plasmodium falciparum, the causative agent of tropical malaria and its role in the general system of malaria control are discussed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3911876", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "[Effect of mosquito contact with DDT and their susceptibility to the causative agent of malaria].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4047719", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "[Lack of an effect from repeated blood sucking by mosquitoes on their infectivity with the causative agent of malaria].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6728514", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The lack of repeated bloodsucking does not affect essentially the infection of Ae. aegypti mosquitoes with malaria agent, P. gallinaceum.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6728514", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "High resolution 31P-NMR has been used for the non-invasive observation of metabolites and metabolic rates in blood of normal mice and of mice infected with Plasmodium berghei, the causative agent of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6760901", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "BACKGROUND: Plasmodium falciparum the main causative agent of malaria is an important public health vector.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382752", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The effectiveness of methylene blue (MB) combined with pyrimethamine (PYR), chloroquine (CQ) or quinine (Q) was examined in a classical four-day suppressive test against a causative agent of rodent malaria, Plasmodium berghei.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22990975", "endSection": "sections.0" }, { "offsetInBeginSection": 351, "offsetInEndSection": 548, "text": "Infection by Plasmodium species, the causative agent of malaria, is currently treated with drug-based therapies, but an increase in drug resistance has led to the need for new methods of treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22592550", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "BACKGROUND: The merozoite surface protein (MSP)-1 of Plasmodium falciparum, the causative agent of malaria tropica, is considered to be a promising vaccine candidate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22095915", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The 23-megabase genome of Plasmodium falciparum, the causative agent of severe human malaria, contains \u223c5300 genes, most of unknown function or lacking homologs in other organisms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22057268", "endSection": "sections.0" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1320, "text": "Results of the present study indicate that malaria is endemic in Nouakchott and that P. vivax is the principal causative agent.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22019287", "endSection": "sections.0" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1413, "text": "Plasmodium vivax was the main causative agent followed by Plasmodium falciparum.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21771420", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Toxoplasma gondii is a member of the phylum Apicomplexa that includes several important human pathogens, such as Cryptosporidium and Plasmodium falciparum, the causative agent of human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21670272", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Plasmodium falciparum, the major causative agent of human malaria, contains three separate genomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21570407", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Plasmodium parasites, the causative agent of malaria, are transmitted through the bites of infected Anopheles mosquitoes resulting in over 250 million new infections each year.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21206476", "endSection": "sections.0" }, { "offsetInBeginSection": 116, "offsetInEndSection": 351, "text": "The genus Plasmodium, causative agent of malaria, of the phylum Apicomplexa, has the smallest mt genome in the form of a circular and/or tandemly repeated linear element of 6 kb, encoding only three protein genes (cox1, cox3, and cob).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20034997", "endSection": "sections.0" }, { "offsetInBeginSection": 141, "offsetInEndSection": 227, "text": "Plasmodium falciparum is the causative agent of the most lethal form of human malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19779742", "endSection": "sections.0" }, { "offsetInBeginSection": 146, "offsetInEndSection": 337, "text": "In Plasmodium falciparum, the causative agent of the most lethal form of malaria, fatty acid biosynthesis occurs in the apicoplast organelle during the liver stage of the parasite life cycle.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19768685", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Plasmodium falciparum, the causative agent of malignant malaria, is among the most severe human infectious diseases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666593", "endSection": "sections.0" }, { "offsetInBeginSection": 34, "offsetInEndSection": 172, "text": "For transmission to occur, Plasmodium, the causative agent of malaria, must complete a complex developmental cycle in its mosquito vector.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19038338", "endSection": "sections.0" }, { "offsetInBeginSection": 267, "offsetInEndSection": 418, "text": "FQ is able to overcome the CQ resistance problem, an important limit to the control of Plasmodium falciparum, the principal causative agent of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19020475", "endSection": "sections.0" }, { "offsetInBeginSection": 272, "offsetInEndSection": 511, "text": "Some lycorine ester derivatives including LT1 were examined for their inhibitory activity against Trypanosoma brucei brucei, the parasite associated with sleeping sickness, and against Plasmodium falciparum, the causative agent of malaria.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19013823", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "A three-dimensional structure of histo-aspartic protease (HAP), a pepsin-like enzyme from the causative agent of malaria Plasmodium falciparum, is suggested on the basis of homologous modeling followed by equilibration by the method of molecular dynamics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18672695", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: Understanding gene regulation in Plasmodium, the causative agent of malaria, is an important step in deciphering its complex life cycle as well as leading to possible new targets for therapeutic applications.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18611947", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Plasmodium falciparum, the causative agent of malaria, relies on a complex protein-secretion system for protein targeting into numerous subcellular destinations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18522993", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "We have evaluated a technology called transcriptionally active PCR (TAP) for high throughput identification and prioritization of novel target antigens from genomic sequence data using the Plasmodium parasite, the causative agent of malaria, as a model.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18164079", "endSection": "sections.0" } ] }, { "body": "What is the major adverse effect of adriamycin(doxorubicin)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15997091", "http://www.ncbi.nlm.nih.gov/pubmed/21295102", "http://www.ncbi.nlm.nih.gov/pubmed/3947104", "http://www.ncbi.nlm.nih.gov/pubmed/12074691", "http://www.ncbi.nlm.nih.gov/pubmed/15114698", "http://www.ncbi.nlm.nih.gov/pubmed/3459397", "http://www.ncbi.nlm.nih.gov/pubmed/3461747", "http://www.ncbi.nlm.nih.gov/pubmed/12445862", "http://www.ncbi.nlm.nih.gov/pubmed/7325994" ], "ideal_answer": [ "Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy ", "Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy. In spite of the routine use of this drug its major adverse effect, the dose-dependent cardiotoxicity, cannot be prevented yet. Cardiotoxicity is a major adverse effect of the anthracycline antibiotics and can be acute or chronic." ], "exact_answer": [ "Cardiotoxicity", "Cardiac toxicity" ], "concepts": [ "http://www.biosemantics.org/jochem#4269440", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004317" ], "type": "factoid", "id": "53551206a0726bee57000001", "snippets": [ { "offsetInBeginSection": 972, "offsetInEndSection": 1158, "text": "It remains to be seen whether inhibition by adriamycin of these systems is related to the severe cardiotoxicity, the major adverse effect of the drug that limits its clinical usefulness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7325994", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1058, "text": "Leukocytopenia was the major adverse effect among patients undergoing systemic THP administration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3947104", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 589, "text": "The major adverse effect was bone-marrow suppression;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3459397", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 866, "text": "The major adverse effect was bone marrow suppression;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3461747", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 746, "text": "Cardiotoxicity is a major adverse effect of the anthracycline antibiotics and can be acute or chronic;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12074691", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1034, "text": "chronic cardiotoxicity represents a serious adverse effect that may be lethal due to the development of irreversible, cumulative dose-dependent, congestive cardiomyopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12074691", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 642, "text": "Myelosuppression, predominantly neutropenia and leucopenia, is the dose-limiting toxicity; in addition to this, mucositis, nausea, vomiting and alopecia are frequent, whereas hepatopathy, characterised by elevated bilirubin concentrations, occurs less frequently", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12074691", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 240, "text": "In spite of the routine use of this drug its major adverse effect, the dose-dependent cardiotoxicity, cannot be prevented yet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12445862", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 434, "text": "The major adverse effect was myelosuppression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15114698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15997091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on doxorubicin-induced cardiotoxicity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15997091", "endSection": "title" }, { "offsetInBeginSection": 55, "offsetInEndSection": 164, "text": "The major adverse effect of DOX treatment in cancer patients is the onset of cardiomyopathy and heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21295102", "endSection": "abstract" } ] }, { "body": "What is GDF10?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8679252", "http://www.ncbi.nlm.nih.gov/pubmed/24963847", "http://www.ncbi.nlm.nih.gov/pubmed/8670277" ], "ideal_answer": [ "The growth/differentiation factor-10 (GDF-10) is a new member of the transforming growth factor-beta (TGF-beta) superfamily. It is highly related to bone morphogenetic protein-3 (BMP-3) and often referred to as BMP3b. The nucleotide sequence of GDF-10 encodes a predicted protein of 476 amino acids with a molecular weight of approximately 52,000. The GDF-10 polypeptide contains a potential signal sequence for secretion, a putative RXXR proteolytic processing site, and a carboxy-terminal domain with considerable homology to other known members of the TGF-beta superfamily. GDF10 is found primarily in murine uterus, adipose tissue, and brain and to a lesser extent in liver and spleen. In addition, GDF-10 mRNA was present in both neonatal and adult bone samples, with higher levels being detected in calvaria than in long bone. These results suggest that GDF10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of mouse chromosome 14 close to a region known to contain a spontaneous recessive mutation that is associated with a craniofacial defect." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055413", "http://www.uniprot.org/uniprot/GDF10_BOVIN", "http://www.uniprot.org/uniprot/GDF10_HUMAN" ], "type": "summary", "id": "56c3104c50c68dd416000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1600, "text": "We have identified a new member of the transforming growth factor-beta (TGF-beta) superfamily, growth/differentiation factor-10 (GDF-10), which is highly related to bone morphogenetic protein-3 (BMP-3). The nucleotide sequence of GDF-10 encodes a predicted protein of 476 amino acids with a molecular weight of approximately 52,000. The GDF-10 polypeptide contains a potential signal sequence for secretion, a putative RXXR proteolytic processing site, and a carboxy-terminal domain with considerable homology to other known members of the TGF-beta superfamily. In the mature carboxy-terminal domain GDF-10 is more homologous to BMP-3 (83% amino acid sequence identity) than to any other previously identified TGF-beta family member. GDF-10 also shows significant homology to BMP-3 (approximately 30% amino acid sequence identity) in the pro- region of the molecule. Based on these sequence comparisons, GDF-10 and BMP-3 define a new subgroup within the larger TGF-beta superfamily. By Northern analysis, GDF-10 mRNA was detected primarily in murine uterus, adipose tissue, and brain and to a lesser extent in liver and spleen. In addition, GDF-10 mRNA was present in both neonatal and adult bone samples, with higher levels being detected in calvaria than in long bone. These results suggest that GDF10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of mouse chromosome 14 close to a region known to contain a spontaneous recessive mutation that is associated with a craniofacial defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8679252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Growth differentiation factor 10 (Gdf10), also known as Bmp3b, is a member of the transforming growth factor (TGF)-\u00df superfamily", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24963847", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1433, "text": "Thus, we show for the first time, that Gdf10, expressed in Bergmann glial cells, is affected by the loss of Shh as early as E18.5, suggesting a regulation of glial development by Shh.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24963847", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1601, "text": "These results suggest that GDF10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of mouse chromosome 14 close to a region known to contain a spontaneous recessive mutation that is associated with a craniofacial defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8679252", "endSection": "abstract" } ] }, { "body": "Is thyroid hormone therapy indicated in patients with heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2189307", "http://www.ncbi.nlm.nih.gov/pubmed/18171701", "http://www.ncbi.nlm.nih.gov/pubmed/17710084", "http://www.ncbi.nlm.nih.gov/pubmed/9485134", "http://www.ncbi.nlm.nih.gov/pubmed/23660007", "http://www.ncbi.nlm.nih.gov/pubmed/8936682", "http://www.ncbi.nlm.nih.gov/pubmed/8936683", "http://www.ncbi.nlm.nih.gov/pubmed/9312172", "http://www.ncbi.nlm.nih.gov/pubmed/15604125", "http://www.ncbi.nlm.nih.gov/pubmed/23369135", "http://www.ncbi.nlm.nih.gov/pubmed/15572044", "http://www.ncbi.nlm.nih.gov/pubmed/19808346", "http://www.ncbi.nlm.nih.gov/pubmed/19778808", "http://www.ncbi.nlm.nih.gov/pubmed/19917524", "http://www.ncbi.nlm.nih.gov/pubmed/10194658", "http://www.ncbi.nlm.nih.gov/pubmed/8333798", "http://www.ncbi.nlm.nih.gov/pubmed/22009366", "http://www.ncbi.nlm.nih.gov/pubmed/12145478", "http://www.ncbi.nlm.nih.gov/pubmed/8353891", "http://www.ncbi.nlm.nih.gov/pubmed/10474790", "http://www.ncbi.nlm.nih.gov/pubmed/12165115", "http://www.ncbi.nlm.nih.gov/pubmed/12165118", "http://www.ncbi.nlm.nih.gov/pubmed/18221125", "http://www.ncbi.nlm.nih.gov/pubmed/19506112", "http://www.ncbi.nlm.nih.gov/pubmed/20100314", "http://www.ncbi.nlm.nih.gov/pubmed/17893267", "http://www.ncbi.nlm.nih.gov/pubmed/19125327", "http://www.ncbi.nlm.nih.gov/pubmed/7954115", "http://www.ncbi.nlm.nih.gov/pubmed/23837113" ], "ideal_answer": [ "There are several experimental and clinical evidences of the potential benefits of Thyroid hormone replacement therapy in heart failure. Initial clinical data showed also a good safety profile and tolerance of TH replacement therapy in patients withheart failure. \nHowever currently there is no indication to treat patients with heart failure withTHreplacementtherapy." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020249", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.disease-ontology.org/api/metadata/DOID:9651", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143" ], "type": "yesno", "id": "531b4269b166e2b80600003e", "snippets": [ { "offsetInBeginSection": 1252, "offsetInEndSection": 1405, "text": "Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23660007", "endSection": "abstract" }, { "offsetInBeginSection": 1613, "offsetInEndSection": 1870, "text": "Early and sustained physiological restoration of circulating L-T3 levels after MI halves infarct scar size and prevents the progression towards heart failure. This beneficial effect is likely due to enhanced capillary formation and mitochondrial protection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100314", "endSection": "abstract" }, { "offsetInBeginSection": 1818, "offsetInEndSection": 2006, "text": "These data indicate that T(3) replacement to euthyroid levels improves systolic function and tends to improve diastolic function, potentially through changes in myocardial gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808346", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 951, "text": "In these patients, the administration of synthetic triiodothyronine (T(3)) was well tolerated and induced significant improvement in cardiac function without increased heart rate and metabolic demand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18221125", "endSection": "abstract" }, { "offsetInBeginSection": 1939, "offsetInEndSection": 2077, "text": "In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18171701", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1277, "text": "Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9485134", "endSection": "abstract" } ] }, { "body": "Is there a mouse model for Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10936049", "http://www.ncbi.nlm.nih.gov/pubmed/12135664", "http://www.ncbi.nlm.nih.gov/pubmed/12200363", "http://www.ncbi.nlm.nih.gov/pubmed/21240276", "http://www.ncbi.nlm.nih.gov/pubmed/9678061", "http://www.ncbi.nlm.nih.gov/pubmed/19561169", "http://www.ncbi.nlm.nih.gov/pubmed/11879775", "http://www.ncbi.nlm.nih.gov/pubmed/22660274", "http://www.ncbi.nlm.nih.gov/pubmed/8879267", "http://www.ncbi.nlm.nih.gov/pubmed/9531583", "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "http://www.ncbi.nlm.nih.gov/pubmed/18812474", "http://www.ncbi.nlm.nih.gov/pubmed/19427003", "http://www.ncbi.nlm.nih.gov/pubmed/21915857" ], "ideal_answer": [ "A number of mouse models have already been generated with a targeted disruption of several Fanconi anemia genes, such as FANCA, FANCF, FANCM, FANCD1, etc." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "yesno", "id": "54edf05494afd6150400000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22660274", "endSection": "title" }, { "offsetInBeginSection": 525, "offsetInEndSection": 702, "text": "We compared Cy preconditioning with fludarabine (Flu) or cytarabine (AraC) or no conditioning as a control in fanca ( -/- ) mutant mice receiving gene-modified bone marrow cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22660274", "endSection": "abstract" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1307, "text": "We conclude that Cy is an effective and superior preparative regimen with respect to engraftment of lentivirus-transduced cells and functional correction in fanca ( -/- ) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22660274", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 485, "text": "To study whether there is a causal relationship between FA pathway defects and tumour development, we have generated a mouse model with a targeted disruption of the FA core complex gene Fancf", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915857", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 752, "text": "Fancf-deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915857", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 1082, "text": "Fancf homozygous mice were viable, born following a normal Mendelian distribution, and showed no growth retardation or developmental abnormalities. The gonads of Fancf mutant mice functioned abnormally, showing compromised follicle development and spermatogenesis as has been observed in other FA mouse models and in FA patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915857", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1190, "text": "In a cohort of Fancf-deficient mice, we observed decreased overall survival and increased tumour incidence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915857", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 393, "text": "To provide further experimental access to the FA-M complementation group we have generated Fancm-deficient mice by deleting exon 2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561169", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 563, "text": "FANCM deficiency caused hypogonadism in mice and hypersensitivity to cross-linking agents in mouse embryonic fibroblasts (MEFs), thus phenocopying other FA mouse models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561169", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 761, "text": "Fancm(Delta2/Delta2) mice also showed unique features atypical for FA mice, including underrepresentation of female Fancm(Delta2/Delta2) mice and decreased overall and tumor-free survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Fancm-deficient mice reveal unique features of Fanconi anemia complementation group M", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561169", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Fancf-deficient mice are prone to develop ovarian tumours", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915857", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812474", "endSection": "title" }, { "offsetInBeginSection": 597, "offsetInEndSection": 874, "text": "Using an FA mouse model with a marked hematopoietic phenotype, the FA-D1 (Brca2(Delta27/Delta27)) mice, we demonstrate that the lentivirus-mediated gene therapy of FA HSCs results in the progressive expansion of genetically corrected clones in mild-conditioned FA-D1 recipients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812474", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1038, "text": "Consistent with these data, hematopoietic progenitors from FA recipients progressively became mitomycin C resistant and their chromosomal instability was reverted", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "We have investigated the hematopoietic phenotype of mice with a hypomorphic mutation in the Brca2/Fancd1 gene (Brca2(Delta27/Delta27) mutation)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 867, "text": "Conventional BM competition experiments showed a marked repopulation defect in Brca2(Delta27/Delta27) hematopoietic stem cells (HSCs), compared to wild-type HSCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1069, "text": "Moreover, we have observed for the first time in a DNA repair disease model a very significant proliferation defect in Brca2(Delta27/Delta27) HSCs maintained in their natural physiological environment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "endSection": "abstract" }, { "offsetInBeginSection": 1291, "offsetInEndSection": 1509, "text": "The hematopoietic phenotype associated with the Brca2(Delta27/Delta27) mutation suggests that this FA-D1 mouse model will constitute an important tool for the development of new therapies for FA, including gene therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200363", "endSection": "title" }, { "offsetInBeginSection": 262, "offsetInEndSection": 463, "text": "In this study we characterized the hematopoietic phenotype of a Fanca knockout mouse model and corrected the main phenotypic characteristics of the bone marrow (BM) progenitors using retroviral vectors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200363", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 630, "text": "The hematopoiesis of these animals was characterized by a modest though significant thrombocytopenia, consistent with reduced numbers of BM megakaryocyte progenitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200363", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 757, "text": "As observed in other FA models, the hematopoietic progenitors from Fanca(-/-) mice were highly sensitive to mitomycin C (MMC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200363", "endSection": "abstract" }, { "offsetInBeginSection": 1303, "offsetInEndSection": 1839, "text": "Aiming to correct the phenotype of Fanca(-/-) progenitors, purified Lin(-)Sca-1(+) cells were transduced with retroviral vectors encoding the enhanced green fluorescent protein (EGFP) gene and human FANCA genes. Lin(-)Sca-1(+) cells from Fanca(-/-) mice were transduced with an efficiency similar to that of samples from wild-type mice. More significantly, transductions with FANCA vectors corrected both the MMC hypersensitivity as well as the impaired ex vivo expansion ability that characterized the BM progenitors of Fanca(-/-) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200363", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1092, "text": " The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21240276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9531583", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812474", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Assessment of the flexed-tail mouse as a possible model for Fanconi anemia: analysis of mitomycin C-induced micronuclei.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8879267", "endSection": "title" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1098, "text": "The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21240276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22660274", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 31, "text": "Mouse models of Fanconi anemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19427003", "endSection": "title" }, { "offsetInBeginSection": 591, "offsetInEndSection": 735, "text": "Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19427003", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 1039, "text": "This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19427003", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 277, "text": "To study FA complementation group A using the mouse as a model system, we cloned and characterized the mouse homolog of the human FANCA cDNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10936049", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 419, "text": "Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21240276", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 734, "text": "Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19427003", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 342, "text": "In contrast to observations made in other Fanconi anemia (FA) mouse models, low numbers of hematopoietic colony-forming cells (CFCs) were noted in Brca2(Delta27/Delta27) mice, either young or adult", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16859999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Fanconi anemia group A and C double-mutant mice: functional evidence for a multi-protein Fanconi anemia complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12135664", "endSection": "title" }, { "offsetInBeginSection": 724, "offsetInEndSection": 796, "text": "In addition, mouse models are also useful for testing treatments for FA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11879775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Development and characterization of immortalized fibroblastoid cell lines from an FA(C) mouse model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9678061", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 411, "text": "These mouse models display the characteristic FA feature of cellular hypersensitivity to DNA cross-linking agents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11879775", "endSection": "abstract" } ] }, { "body": "Could Hyperthermic intraperitoneal chemotherapy (HIPEC) be effective for the treatment of recurrent ovarian cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24035502", "http://www.ncbi.nlm.nih.gov/pubmed/22591422", "http://www.ncbi.nlm.nih.gov/pubmed/20039210", "http://www.ncbi.nlm.nih.gov/pubmed/19345401", "http://www.ncbi.nlm.nih.gov/pubmed/19701772", "http://www.ncbi.nlm.nih.gov/pubmed/21842290", "http://www.ncbi.nlm.nih.gov/pubmed/19948452", "http://www.ncbi.nlm.nih.gov/pubmed/23226073", "http://www.ncbi.nlm.nih.gov/pubmed/19917539", "http://www.ncbi.nlm.nih.gov/pubmed/24675244", "http://www.ncbi.nlm.nih.gov/pubmed/18473354", "http://www.ncbi.nlm.nih.gov/pubmed/23022234", "http://www.ncbi.nlm.nih.gov/pubmed/21112721", "http://www.ncbi.nlm.nih.gov/pubmed/22845405", "http://www.ncbi.nlm.nih.gov/pubmed/19356887", "http://www.ncbi.nlm.nih.gov/pubmed/23972918", "http://www.ncbi.nlm.nih.gov/pubmed/22591426", "http://www.ncbi.nlm.nih.gov/pubmed/20721959", "http://www.ncbi.nlm.nih.gov/pubmed/22572845", "http://www.ncbi.nlm.nih.gov/pubmed/24962381", "http://www.ncbi.nlm.nih.gov/pubmed/21543112" ], "ideal_answer": [ "There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials ", "Yes. In the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010051", "http://www.disease-ontology.org/api/metadata/DOID:2394" ], "type": "yesno", "id": "553fb11fc6a5098552000003", "snippets": [ { "offsetInBeginSection": 1311, "offsetInEndSection": 1658, "text": "The use of HIPEC after aggressive cytoreductive surgery in patients with ovarian cancer with peritoneal dissemination can be performed with acceptable postoperative morbidity rates. Knowledge of the factors associated with the onset of these postoperative adverse events allows better management of the same and offers the patient a safe procedure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035502", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1272, "text": "These results showed that the association of HIPEC with a complete cytoreduction for recurrent ovarian cancer presents acceptable morbidity and survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23972918", "endSection": "abstract" }, { "offsetInBeginSection": 1742, "offsetInEndSection": 2184, "text": "There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23226073", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1190, "text": " The combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022234", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 910, "text": " Cautious extrapolation of data from standard normothermic, nonintraoperative, intraperitoneal chemotherapy and data from Phase II and nonrandomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22845405", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1311, "text": "The available evidence suggests that a potential survival benefit of adding HIPEC may be largest in the settings of secondary CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure of initial standard therapy. There is much less evidence for a potential benefit of HIPEC for less advanced stages (I-II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22591422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22591422", "endSection": "title" }, { "offsetInBeginSection": 714, "offsetInEndSection": 1002, "text": "Patients suffering from peritoneal recurrence of ovarian cancer should be considered for radical reoperation with HIPEC in a center with expertise in multimodal therapeutic options. Organ-preserving cytoreductive surgery allows complete cytoreduction with the goal of decreasing morbidity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21842290", "endSection": "abstract" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1458, "text": " In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21543112", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1311, "text": " The results of our study indicate the feasibility and the potential benefit of a protocol including systemic chemotherapy, surgical cytoreduction and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. A phase III trial to compare this approach with conventional treatment is needed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20721959", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1461, "text": "In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20039210", "endSection": "abstract" }, { "offsetInBeginSection": 1488, "offsetInEndSection": 1763, "text": " HIPEC is a complement to radical surgery/ peritonectomy, which has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival and prolonged disease-free interval in patients with peritoneal carcinomatosis for recurrent ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19917539", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1731, "text": " Despite the heterogeneity of the studies reviewed, current evidence suggest that complete CRS and HIPEC may be a feasible option with potential benefits that are comparable with the current standard of care. A randomized trial is required to establish the role of HIPEC in ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19701772", "endSection": "abstract" }, { "offsetInBeginSection": 1384, "offsetInEndSection": 1597, "text": "in the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19356887", "endSection": "abstract" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1674, "text": " Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18473354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24962381", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22591422", "endSection": "title" }, { "offsetInBeginSection": 213, "offsetInEndSection": 433, "text": "Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572845", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 954, "text": "Trabectedin, Hyperthermic intraperitoneal chemotherapy (HIPEC) and chemo-immunotherapy may be become a promising therapy for the treatment of ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22591426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112721", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 262, "text": "Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948452", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 434, "text": "Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675244", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 261, "text": "Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "[Importance of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948452", "endSection": "title" } ] }, { "body": "Which is the most common editing modification in eukaryotic mRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20198873", "http://www.ncbi.nlm.nih.gov/pubmed/25577380", "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "http://www.ncbi.nlm.nih.gov/pubmed/23346095", "http://www.ncbi.nlm.nih.gov/pubmed/21469143", "http://www.ncbi.nlm.nih.gov/pubmed/20185571", "http://www.ncbi.nlm.nih.gov/pubmed/25373143" ], "ideal_answer": [ "One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation." ], "exact_answer": [ "A-to-I" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012333", "http://amigo.geneontology.org/amigo/term/GO:0016556", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017393", "http://amigo.geneontology.org/amigo/term/GO:0009451" ], "type": "factoid", "id": "56ffdc1ccf1c32585100000b", "snippets": [ { "offsetInBeginSection": 205, "offsetInEndSection": 364, "text": "One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185571", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 404, "text": "Deamination of adenine by adenosine deaminases that act on RNA (ADARs) leads to the conversion of adenine into inosine (A-I editing) recognized by the splicing and translation systems as guanine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20198873", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1065, "text": "denosine deaminases editing adenines in transport RNAs (ADATs) convert adenine into inosine in tRNAs of all eukaryotes; as a result, the diversity of tRNA forms in the cell increases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20198873", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 131, "text": "A-to-I editing events in normal and cancerous human keratinocytes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "title" }, { "offsetInBeginSection": 430, "offsetInEndSection": 543, "text": "A-to-I RNA editing can alter codons, substitute amino acids and affect protein sequence, structure, and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 428, "text": "-to-I RNA editing is a post-transcriptional mechanism frequently used to expand and diversify transcriptome and proteome repertoire in eukaryotic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1603, "text": "This study describes for the first time A-to-I editing in the coding sequence of a tumor suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine-tuning mechanism to maintain the equilibrium between proliferation and senescence in normal skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 255, "text": "Adenosine deaminases that act on RNA (ADARs) catalyze the adenosine-to-inosine (A-to-I) conversion, the most common type of RNA editing in higher eukaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25373143", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 371, "text": "RNA editing is observed in eukaryotic mRNA, transfer RNA, ribosomal RNA, and non-coding RNAs (ncRNA). The most common RNA editing in the mammalian central nervous system is a base modification, where the adenosine residue is base-modified to inosine (A to I).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23346095", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 365, "text": "It occurs in a wide variety of eukaryotic organisms and in some viruses. One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185571", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 371, "text": "The most common RNA editing in the mammalian central nervous system is a base modification, where the adenosine residue is base-modified to inosine (A to I).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23346095", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 365, "text": "One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185571", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 485, "text": "RNA editing by adenosine deamination (A-to-I) is widespread in humans and can lead to a variety of biological effects depending on the RNA type or the RNA region involved in the editing modification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25577380", "endSection": "abstract" } ] }, { "body": "Is Rac1 involved in cancer cell invasion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20001211", "http://www.ncbi.nlm.nih.gov/pubmed/23242308", "http://www.ncbi.nlm.nih.gov/pubmed/21377450", "http://www.ncbi.nlm.nih.gov/pubmed/23554696", "http://www.ncbi.nlm.nih.gov/pubmed/20307526", "http://www.ncbi.nlm.nih.gov/pubmed/21776386", "http://www.ncbi.nlm.nih.gov/pubmed/22745590", "http://www.ncbi.nlm.nih.gov/pubmed/16280046", "http://www.ncbi.nlm.nih.gov/pubmed/21698524", "http://www.ncbi.nlm.nih.gov/pubmed/17671188", "http://www.ncbi.nlm.nih.gov/pubmed/22955285", "http://www.ncbi.nlm.nih.gov/pubmed/19684614", "http://www.ncbi.nlm.nih.gov/pubmed/22161837", "http://www.ncbi.nlm.nih.gov/pubmed/21281602", "http://www.ncbi.nlm.nih.gov/pubmed/23876400", "http://www.ncbi.nlm.nih.gov/pubmed/23382862" ], "ideal_answer": [ "A number of signalling pathways have been found to converge to and activate Rac1, which, in turn, activates a number of downstream targets to control actin-cytoskeleton rearrangements at membrane ruffles, as well as formation and activity of lamellipodia, to regulate the migratory processes leading to cell invasion." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/ACT1_ORYSJ", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009361", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.uniprot.org/uniprot/RAC1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020830" ], "type": "yesno", "id": "5319abc9b166e2b80600002d", "snippets": [ { "offsetInBeginSection": 1012, "offsetInEndSection": 1168, "text": "In the Matrigel invasion assay, knockdown of CCR1 and inhibition of the ERK and Rac signaling pathways significantly decreased the number of invading cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23876400", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1652, "text": "These results demonstrated for the first time that the interaction of CCR1 with CCL5 caused by increased expression of CCR1 promotes invasion of PC3PR cells by increasing secretion of MMPs 2 and 9 and by activating ERK and Rac signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23876400", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1111, "text": "These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382862", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1254, "text": "Activated PAR1 induced RhoA and Rac1 phosphorylation, and subsequent overexpression of myosin IIA and filamin B which are stress fiber components that were identified by PMF analysis of peptide mass data obtained by MALDI-TOF/MS measurement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242308", "endSection": "abstract" }, { "offsetInBeginSection": 1536, "offsetInEndSection": 1785, "text": "These results demonstrate that PAR1 activation induces cell morphological change associated with cell motility via Rho family activation and cytoskeletal protein overexpression, and has a critical role in gastric cancer cell invasion and metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242308", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1033, "text": "Rac1 was found to be required for actopaxin-induced matrix degradation whereas inhibition of myosin contractility promoted degradation in the phosphomutant-expressing Quint cells, indicating that a balance of Rho GTPase signaling and regulation of cellular tension are important for the process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955285", "endSection": "abstract" }, { "offsetInBeginSection": 1498, "offsetInEndSection": 1658, "text": "Taken together, this study demonstrates a new role for actopaxin phosphorylation in matrix degradation and cell invasion via regulation of Rho GTPase signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "BART inhibits pancreatic cancer cell invasion by Rac1 inactivation through direct binding to active Rac1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22745590", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "We report that Binder of Arl Two (BART) plays a role in inhibiting cell invasion by regulating the activity of the Rho small guanosine triphosphatase protein Rac1 in pancreatic cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22745590", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 779, "text": "BART interacts with active forms of Rac1, and the BART-Rac1 complex localizes at the leading edges of migrating cancer cells. Suppression of BART increases active Rac1, thereby increasing cell invasion. Treatment of pancreatic cancer cells in which BART is stably knocked down with a Rac1 inhibitor decreases invasiveness. Thus, BART-dependent inhibition of cell invasion is likely associated with decreased active Rac1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22745590", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1044, "text": "The Rac1 inhibitor inhibits the lamellipodia formation that is stimulated by suppression of BART.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22745590", "endSection": "abstract" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1238, "text": "Our results imply that BART regulates actin-cytoskeleton rearrangements at membrane ruffles through modulation of the activity of Rac1, which, in turn, inhibits pancreatic cancer cell invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22745590", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 1387, "text": "It has been reported as an important inducer of cancer cell migration and invasion, with underlying molecular mechanisms involving the signalling mediated by its juxtamembrane domain, the secretion of matrix metalloproteases to the extracellular media, and the cleavage of a P-cadherin soluble form with pro-invasive activity. Intracellularly, this protein interferes with the endogenous cadherin/catenin complex, inducing p120-catenin delocalization to the cytoplasm, and the consequent activation of Rac1/Cdc42 and associated alterations in the actin cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22161837", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 365, "text": "Targeted down-regulation of RhoC led to sustained activation of Rac1 GTPase and morphological, molecular and phenotypic changes reminiscent of epithelial to mesenchymal transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21776386", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1061, "text": "We also find that Rac1 GTPase mediates tight binding of prostate cancer cells to bone marrow endothelial cells and promotes retraction of endothelial cells required for tumor cell diapedesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21776386", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1191, "text": "Finally, Rac1 leads to \u03b21 integrin activation, suggesting a mechanism that Rac1 can mediate tight binding with endothelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21776386", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1318, "text": "Together, our data suggest that Rac1 GTPase is key mediator of prostate cancer cell-bone marrow endothelial cell interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21776386", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 754, "text": "Furthermore, expression of dominant-negative Rac1 (T17N) could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23554696", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1176, "text": "Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Rac1, generation of ROS and subsequent activation of PI3K/Akt and PAK1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23554696", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 234, "text": "Small GTPase proteins, including RhoA, RhoB, RhoC, Rac1, and cdc42, are important molecules for linking cell shape and cell-cycle progression because of their role in both cytoskeletal arrangements and mitogenic signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21698524", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 650, "text": "The suppression of MMP-2 expression by CTXG led to an inhibition of SW620 cells invasion and migration by inactivating Rac1 and Cdc42 but not RhoA GTPase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21377450", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 950, "text": "In conclusion, our data demonstrate that CTXG exerted anti-invasion action in SW620 cells by targeting MMP-2 though regulating the activities of Rac1, Cdc42 and their downstream transcriptional factor AP-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21377450", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 133, "text": "ctivation of H-Ras and Rac1 correlates with epidermal growth factor-induced invasion in Hs578T and MDA-MB-231 breast carcinoma cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21281602", "endSection": "title" }, { "offsetInBeginSection": 211, "offsetInEndSection": 363, "text": "We have previously shown that H-Ras, but not N-Ras, induces an invasive phenotype mediated by small GTPase Rac1 in MCF10A human breast epithelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21281602", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1092, "text": "Moreover, siRNA-knockdown of Rac1 significantly inhibited the EGF-induced invasiveness in these cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21281602", "endSection": "abstract" }, { "offsetInBeginSection": 1265, "offsetInEndSection": 1507, "text": "Our data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion, providing important information on the regulation of malignant progression in mammary carcinoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21281602", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 602, "text": "At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20307526", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1222, "text": "These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20307526", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 996, "text": "RhoGDI2 modulates the invasiveness and metastatic ability of cancer cells through regulation of Rac1 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20001211", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 967, "text": "We also showed that GBM cells secrete Sema3A endogenously, and RNA interference-mediated downregulation of Sema3A inhibits migration and alters cell morphology that is dependent on Rac1 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19684614", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 106, "text": "LMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671188", "endSection": "title" }, { "offsetInBeginSection": 345, "offsetInEndSection": 588, "text": "Here, we report for the first time that engulfment and cell motility 1 (ELMO1) and dedicator of cytokinesis 1 (Dock180), a bipartite Rac1 guanine nucleotide exchange factor (GEF), are evidently linked to the invasive phenotype of glioma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671188", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1118, "text": "Inhibition of endogenous ELMO1 and Dock180 expression significantly impeded glioma cell invasion in vitro and in brain tissue slices with a concomitant reduction in Rac1 activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17671188", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 562, "text": "Members of the Rac family of small GTPases are known to act as regulators of actin cytoskeletal structures and strongly influence the cellular processes of integrin-mediated adhesion and migration. Even though hyperactivated Rac proteins have been shown to influence metastatic processes, these proteins have never been directly linked to metastatic progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16280046", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1554, "text": "We show that increased activation of Rac proteins directly correlates with increasing metastatic potential in a panel of cell variants derived from a single metastatic breast cancer cell line (MDA-MB-435).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16280046", "endSection": "abstract" }, { "offsetInBeginSection": 1617, "offsetInEndSection": 1729, "text": "Expression of a dominant active Rac1 or a dominant active Rac3 resulted in a more invasive and motile phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16280046", "endSection": "abstract" }, { "offsetInBeginSection": 1730, "offsetInEndSection": 1901, "text": "Moreover, expression of either dominant negative Rac1 or dominant negative Rac3 into the most metastatic cell variant resulted in decreased invasive and motile properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16280046", "endSection": "abstract" }, { "offsetInBeginSection": 1914, "offsetInEndSection": 2209, "text": "This study correlates endogenous Rac activity with high metastatic potential and implicates Rac in the regulation of cell migration and invasion in metastatic breast cancer cells. Taken together, these results suggest a role for both the Rac1 and Rac3 GTPases in human breast cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16280046", "endSection": "abstract" } ] }, { "body": "Which are the APOBEC3 protein family members able to inhibit Vif-deficient HIV-1 replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21279453", "http://www.ncbi.nlm.nih.gov/pubmed/15466872", "http://www.ncbi.nlm.nih.gov/pubmed/23427247", "http://www.ncbi.nlm.nih.gov/pubmed/23316055", "http://www.ncbi.nlm.nih.gov/pubmed/22787460", "http://www.ncbi.nlm.nih.gov/pubmed/18495196", "http://www.ncbi.nlm.nih.gov/pubmed/24189052", "http://www.ncbi.nlm.nih.gov/pubmed/21835787", "http://www.ncbi.nlm.nih.gov/pubmed/19036809", "http://www.ncbi.nlm.nih.gov/pubmed/15296758", "http://www.ncbi.nlm.nih.gov/pubmed/17522216" ], "ideal_answer": [ "APOBEC3G, APOBEC3F, APOBEC3DE, APOBEC3A, and APOBEC3H haplotypes II, V, and VII, provide protection against Vif-deficient HIV-1, through hypermutation of the viral genome, inhibition of reverse transcription, and inhibition of viral DNA integration into the host genome." ], "exact_answer": [ [ "APOBEC3G" ], [ "APOBEC3F" ], [ "APOBEC3DE" ], [ "APOBEC3A" ], [ "APOBEC3H haplotypes II, V, and VII" ] ], "concepts": [ "http://www.uniprot.org/uniprot/ABEC3_MOUSE", "http://www.uniprot.org/uniprot/ABEC3_CRILO", "http://www.uniprot.org/uniprot/ABEC3_RAT" ], "type": "list", "id": "54de15f91388e8454a000002", "snippets": [ { "offsetInBeginSection": 148, "offsetInEndSection": 395, "text": "APOBEC3DE, APOBEC3F, APOBEC3G, and APOBEC3H haplotypes II, V, and VII provide protection against HIV-1\u0394vif through hypermutation of the viral genome, inhibition of reverse transcription, and inhibition of viral DNA integration into the host genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24189052", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 834, "text": "low quantities of IFN-\u03b1 failed to upregulate costimulatory molecules, did not induce IL-12p40 or migration, but significantly induced A3G, A3A, and A3F mRNA expression and restricted viral replication in MDDCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23427247", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 493, "text": "Without Vif, A3 proteins, particularly APOBEC3G (A3G) and APOBEC3F (A3F), inhibit HIV-1 replication by blocking reverse transcription and/or integration and hypermutating nascent viral cDNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787460", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 835, "text": "In addition to APOBEC3G, we find that three other human APOBEC3 proteins, APOBEC3D, APOBEC3F, and APOBEC3H, are all potent HIV-1 restriction factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835787", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1542, "text": "These data strongly implicate a combination of four APOBEC3 proteins--APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H--in HIV-1 restriction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835787", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1282, "text": "Furthermore, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H of the rhesus macaque also are packaged into and restrict Vif-deficient HIV-1 when stably expressed in T cells, and they are all neutralized by the simian immunodeficiency virus Vif protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "APOBEC3G is a retroviral restriction factor that can inhibit the replication of human immunodeficiency virus, type 1 (HIV-1) in the absence of the viral infectivity factor (Vif) protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835787", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The human APOBEC3 (A3) cytidine deaminases, such as APOBEC3G (A3G) and APOBEC3F (A3F), are potent inhibitors of Vif-deficient human immunodeficiency virus type 1 (HIV-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21279453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Human APOBEC3G (A3G) and APOBEC3F (A3F) inhibit the replication of Vif-deficient human immunodeficiency virus type 1 (HIV-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19036809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Human cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) inhibit replication of Vif-deficient human immunodeficiency virus type 1 (HIV-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17522216", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Human APOBEC3G and other APOBEC3 cytidine deaminases inhibit a variety of retroviruses, including Vif-deficient HIV-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18495196", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 556, "text": "Three of these, rat APOBEC1, mouse APOBEC3, and human APOBEC3B, are able to inhibit HIV infectivity even in the presence of Vif", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15296758", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 343, "text": "Two members of this family, APOBEC3G and APOBEC3F, have been found to have potent activity against virion infectivity factor deficient (Deltavif) human immunodeficiency virus 1 (HIV-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15466872", "endSection": "abstract" } ] }, { "body": "Is the gene SLC6A2 associated with orthostatic intolerance?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23580201", "http://www.ncbi.nlm.nih.gov/pubmed/12589229", "http://www.ncbi.nlm.nih.gov/pubmed/22723437", "http://www.ncbi.nlm.nih.gov/pubmed/11458707", "http://www.ncbi.nlm.nih.gov/pubmed/12391111", "http://www.ncbi.nlm.nih.gov/pubmed/15894713", "http://www.ncbi.nlm.nih.gov/pubmed/12805287" ], "ideal_answer": [ "Yes, variants of the SLC6A2 (or NET) gene are associated with orthostatic intolerance." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054971" ], "type": "yesno", "id": "56d8ba1851531f7e33000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12391111", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1324, "text": "Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12391111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805287", "endSection": "title" }, { "offsetInBeginSection": 174, "offsetInEndSection": 334, "text": " Recently, our laboratory reported a polymorphism in the human NET (hNET) gene A457P in an individual with the autonomic disorder orthostatic intolerance (OI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805287", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 578, "text": "Nonsynonymous single nucleotide polymorphisms (SNPs) in the human NET (hNET) gene that influence transporter function can contribute to disease, such as the nonfunctional transporter, A457P, identified in orthostatic intolerance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15894713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Orthostatic intolerance is not necessarily related to a specific mutation (Ala457Pro) in the human norepinephrine transporter gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12589229", "endSection": "title" }, { "offsetInBeginSection": -1, "offsetInEndSection": 117, "text": "We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723437", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 457, "text": "The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723437", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1383, "text": "In the absence of altered SLC6A2 gene sequence or promoter methylation, this reduced expression was directly correlated with chromatin modifications. We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723437", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 458, "text": "A coding mutation in the norepinephrine transporter gene (SLC6A2) sequence has been reported in 1 family kindred only. The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723437", "endSection": "abstract" } ] }, { "body": "Other than protein coding potential, what features set apart long non-coding RNAs from protein coding genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21502407", "http://www.ncbi.nlm.nih.gov/pubmed/22546862", "http://www.ncbi.nlm.nih.gov/pubmed/23274483", "http://www.ncbi.nlm.nih.gov/pubmed/19895688", "http://www.ncbi.nlm.nih.gov/pubmed/21112873", "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "http://www.ncbi.nlm.nih.gov/pubmed/22071789", "http://www.ncbi.nlm.nih.gov/pubmed/22135294", "http://www.ncbi.nlm.nih.gov/pubmed/22303401", "http://www.ncbi.nlm.nih.gov/pubmed/21915789", "http://www.ncbi.nlm.nih.gov/pubmed/23463798", "http://www.ncbi.nlm.nih.gov/pubmed/17387145", "http://www.ncbi.nlm.nih.gov/pubmed/20587619", "http://www.ncbi.nlm.nih.gov/pubmed/23319885" ], "ideal_answer": [ "Compared to protein coding genes, long non-coding RNAs (lncRNAs) display a bias towards two-exon transcripts. They are predominantly localized in the chromatin and nucleous. They are lower expressed and display a more tissue-specific expression pattern. LncRNAs are overall more weakly conserved than protein coding genes." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022661", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085" ], "type": "summary", "id": "5172e9448ed59a060a000018", "snippets": [ { "offsetInBeginSection": 546, "offsetInEndSection": 739, "text": "Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "sections.0" }, { "offsetInBeginSection": 740, "offsetInEndSection": 845, "text": "In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "sections.0" }, { "offsetInBeginSection": 848, "offsetInEndSection": 979, "text": "hey are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "sections.0" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1166, "text": "They are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "sections.0" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1532, "text": "Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "endSection": "sections.0" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1242, "text": "he proportion of conserved sequence (4.1%-5.5%) in these macroRNAs is comparable to the density of exons within protein-coding transcripts (5.2%). These macroRNAs, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387145", "endSection": "sections.0" } ] }, { "body": "Is macitentan an ET agonist?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22862294", "http://www.ncbi.nlm.nih.gov/pubmed/23830395", "http://www.ncbi.nlm.nih.gov/pubmed/25539851", "http://www.ncbi.nlm.nih.gov/pubmed/24797866", "http://www.ncbi.nlm.nih.gov/pubmed/23984728", "http://www.ncbi.nlm.nih.gov/pubmed/24769543", "http://www.ncbi.nlm.nih.gov/pubmed/23900878", "http://www.ncbi.nlm.nih.gov/pubmed/23077657", "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "http://www.ncbi.nlm.nih.gov/pubmed/24297706", "http://www.ncbi.nlm.nih.gov/pubmed/25060980", "http://www.ncbi.nlm.nih.gov/pubmed/24998329", "http://www.ncbi.nlm.nih.gov/pubmed/21403842", "http://www.ncbi.nlm.nih.gov/pubmed/25457902", "http://www.ncbi.nlm.nih.gov/pubmed/24906252", "http://www.ncbi.nlm.nih.gov/pubmed/25226600", "http://www.ncbi.nlm.nih.gov/pubmed/25604973", "http://www.ncbi.nlm.nih.gov/pubmed/23353592", "http://www.ncbi.nlm.nih.gov/pubmed/25131455", "http://www.ncbi.nlm.nih.gov/pubmed/25084082", "http://www.ncbi.nlm.nih.gov/pubmed/23568224", "http://www.ncbi.nlm.nih.gov/pubmed/25012164", "http://www.ncbi.nlm.nih.gov/pubmed/22348175", "http://www.ncbi.nlm.nih.gov/pubmed/22189899", "http://www.ncbi.nlm.nih.gov/pubmed/20730702", "http://www.ncbi.nlm.nih.gov/pubmed/22525377", "http://www.ncbi.nlm.nih.gov/pubmed/25377471", "http://www.ncbi.nlm.nih.gov/pubmed/24582812", "http://www.ncbi.nlm.nih.gov/pubmed/23997048" ], "ideal_answer": [ "No, macitentan is anendothelin receptor antagonist." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065128", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065131", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065130" ], "type": "yesno", "id": "56c863385795f9a73e000015", "snippets": [ { "offsetInBeginSection": 865, "offsetInEndSection": 1036, "text": "Administration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced MMT, fibrosis, angiogenesis, and peritoneal functional decline. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25012164", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 453, "text": "Macitentan is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with high affinity and sustained receptor binding that was approved in the USA, Europe, Canada, and Switzerland for the treatment of PAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25604973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Macitentan (Opsumit\u00ae) is a novel dual endothelin receptor antagonist (ERA) with sustained receptor binding properties developed by Actelion Pharmaceuticals Ltd.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 520, "text": "Macitentan, also called Actelion-1 or ACT-064992 [N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-N'-propylaminosulfonamide], is a new dual ET(A)/ET(B) endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on inhibitory potency on both ET receptors and optimization of physicochemical properties to achieve high affinity for lipophilic milieu. In vivo, macitentan is metabolized into a major and pharmacologically active metabolite, ACT-132577. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 1183, "text": "Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET(A) receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET(B) receptors). In rats with pulmonary hypertension, macitentan prevented both the increase of pulmonary pressure and the right ventricle hypertrophy, and it markedly improved survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1689, "text": "In conclusion, macitentan, by its tissue-targeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats. This profile makes macitentan a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18780830", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525377", "endSection": "title" }, { "offsetInBeginSection": 230, "offsetInEndSection": 498, "text": "Here we investigated the effects of macitentan, an orally-active, tissue-targeting dual ET receptor antagonist on chronic complications in type 2 diabetes.MAIN METHODS: db/db mice and their age- and sex-matched controls were examined after 2 and 4 months of diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525377", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 314, "text": "Macitentan is a novel dual ETA/ETB receptor antagonist with enhanced tissue distribution and sustained receptor binding properties designed to achieve a more efficacious ET receptor blockade. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24582812", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 867, "text": "Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997048", "endSection": "abstract" } ] }, { "body": "Can we use platelet biomarkers to study Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22579745", "http://www.ncbi.nlm.nih.gov/pubmed/24175175", "http://www.ncbi.nlm.nih.gov/pubmed/22674539" ], "ideal_answer": [ "Yes, platelet biomarkers can be used to study Alzheimer's disease." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ], "type": "yesno", "id": "530b4f49970c65fa6b00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Platelet biomarkers in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24175175", "endSection": "title" }, { "offsetInBeginSection": 1307, "offsetInEndSection": 1474, "text": "platelets are the most important source of circulating forms of the amyloid precursor protein and other important proteins such as Tau and glycogen synthase kinase-3B.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24175175", "endSection": "abstract" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1334, "text": "Alternative plasma and platelet measures are described,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22674539", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 970, "text": "The success of these studies led to the application of platelet proteomics to the study of several pathologies where platelets play a fundamental role. Those include platelet-related disorders, such as storage pool disease, gray platelet syndrome, and Quebec platelet disorder; diseases where unwanted platelet activation is highly relevant, such as thrombosis and cardiovascular disease; and other diseases, such as cystic fibrosis, uremia, or Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22579745", "endSection": "abstract" } ] }, { "body": "Which genetic defects are observed in Prader-Willi syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9629378", "http://www.ncbi.nlm.nih.gov/pubmed/9613204", "http://www.ncbi.nlm.nih.gov/pubmed/1608955", "http://www.ncbi.nlm.nih.gov/pubmed/14749005", "http://www.ncbi.nlm.nih.gov/pubmed/21798057", "http://www.ncbi.nlm.nih.gov/pubmed/18627056", "http://www.ncbi.nlm.nih.gov/pubmed/18086025", "http://www.ncbi.nlm.nih.gov/pubmed/8630505", "http://www.ncbi.nlm.nih.gov/pubmed/8957518" ], "ideal_answer": [ "The predominant genetic defects in Prader-Willi syndrome are 15q11-13 deletions of paternal origin and maternal chromosome 15 uniparental disomy, or rare imprinting mutations, combined with monoallelic expression of the paternal alleles." ], "exact_answer": [ [ "15q11-13 deletions of paternal origin" ], [ "maternal chromosome 15 uniparental disomy" ], [ "rare imprinting mutations" ], [ "monoallelic expression of the paternal alleles" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11983", "http://www.disease-ontology.org/api/metadata/DOID:630", "http://www.disease-ontology.org/api/metadata/DOID:0050325", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011218", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006349", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071514", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018392" ], "type": "list", "id": "5306158358348c0f52000001", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 148, "text": "Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21798057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Prader-Willi syndrome (PWS) is caused by the disturbed expression of genes from the imprinted region of 15q11-q13, but the specific contributions of individual genes remain unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18627056", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 127, "text": "Prader-Willi syndrome (PWS) is a rare disorder caused by genetic defects in certain regions of chromosome 15q11-13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18086025", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 207, "text": "Prader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14749005", "endSection": "abstract" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1628, "text": "Genomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14749005", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 378, "text": "Abnormalities in imprinted inheritance occur in several genetic diseases and cancer, and are exemplified by the diverse genetic defects involving chromosome 15q11-q13 in Prader-Willi (PWS) and Angelman (AS) syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9613204", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 293, "text": "The predominant genetic defects in PW are 15q11-13 deletions of paternal origin and maternal chromosome 15 uniparental disomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9629378", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 553, "text": "In both disorders, these mutations are associated with parent-of-origin specific methylation at several 15q11-13 loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9629378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Prader-Willi syndrome (PWS) is caused by absence of a paternal contribution of the chromosome region 15q11-q13, resulting from paternal deletions, maternal uniparental disomy, or rare imprinting mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8957518", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1546, "text": "Because methylation analysis can detect all three major classes of genetic defects associated with PWS (deletion, UPD, or imprinting mutations), methylation analysis with either PW71 or SNRPN is an efficient primary screening test to rule out a diagnosis of PWS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8957518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The predominant genetic defects in Prader-Willi syndrome (PWS) are 15q11-q13 deletions of paternal origin and maternal chromosome 15 uniparental disomy (UPD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8630505", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 681, "text": "In both disorders, these mutations are associated with parent-of-origin specific methylation at several 15q11-q13 loci. The critical PWS region has been narrowed to a approximately 320-kb region between D15S63 and D15S174, encoding several imprinted transcripts, including PAR5, IPW, PAR1 (refs 7,8) and SNRPN, which has so far been considered a strong candidate for the PWS gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8630505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The genetic defects in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) map to 15q11-13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1608955", "endSection": "abstract" } ] }, { "body": "What is the most likely age of diagnosis of Crohn's disease (CD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22685044", "http://www.ncbi.nlm.nih.gov/pubmed/19107777", "http://www.ncbi.nlm.nih.gov/pubmed/18236809", "http://www.ncbi.nlm.nih.gov/pubmed/23880115", "http://www.ncbi.nlm.nih.gov/pubmed/23511037", "http://www.ncbi.nlm.nih.gov/pubmed/9412954", "http://www.ncbi.nlm.nih.gov/pubmed/8780560", "http://www.ncbi.nlm.nih.gov/pubmed/16534420", "http://www.ncbi.nlm.nih.gov/pubmed/22918090", "http://www.ncbi.nlm.nih.gov/pubmed/20844954", "http://www.ncbi.nlm.nih.gov/pubmed/26089697", "http://www.ncbi.nlm.nih.gov/pubmed/21488915" ], "ideal_answer": [ "Crohn's disease has a bimodal age distribution of disease onset diagnosis. The peaks (20 and 50 years) may represent different phenotypes or different genetic and/or environmental influences between younger- and older-onset individuals. When the age-related incidence of Crohn's disease was plotted for all countries from which such data were available, the peaks of greatest case frequency occurred at ages 15 to 25 years and paralleled a similar peak representing the number of Peyer's patches as a function of age. For those with biologic use, average age at time of diagnosis of Crohn's disease was 32.3 \u00b1 12.2 years, compared with 43.7 \u00b1 16.3 years for those who had not received biologics (P = 0.005)." ], "exact_answer": [ "Crohn's disease has a bimodal age distribution of disease onset diagnosis. The peaks (20 and 50 years) may represent different phenotypes or different genetic and/or environmental influences between younger- and older-onset individuals." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003424", "http://www.disease-ontology.org/api/metadata/DOID:4" ], "type": "factoid", "id": "56cae3eb5795f9a73e000021", "snippets": [ { "offsetInBeginSection": 1077, "offsetInEndSection": 1168, "text": "Eighteen, 17, and 12 patients were diagnosed at ages<40, 40-59, and \u226560 years, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26089697", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 218, "text": "Crohn's disease (CD) diagnosed in pediatric patients has been reported to have a more aggressive phenotype and course, with a greater prevalence of upper gastrointestinal involvement, than in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880115", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 659, "text": "There was a significant association between body mass index and bone mineral density (P = 0.004) and a significant difference in the T scores of patients according to age at diagnosis (Montreal Classification: P = 0.0006) with patients diagnosed<17 years (n = 13) having lower T scores than those diagnosed at older age groups (n = 70).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23511037", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1083, "text": "Increasing age of diagnosis was negatively associated with complicated disease and positively associated with colonic disease. As age of diagnosis increased, disease duration (P<0.001), family history of Inflammatory bowel disease (IBD) (P = 0.015) and perianal disease decreased (P<0.0015). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918090", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1068, "text": "Crohn's disease incidence rates in the 10-19-year age category increased by 71%, from 6.5 (1988-1990) to 11.1 (2006-2007)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21488915", "endSection": "abstract" }, { "offsetInBeginSection": 1395, "offsetInEndSection": 1502, "text": "Consequently, studies on Crohn's disease risk factors should focus on the population under 20 years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21488915", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 825, "text": "For those with biologic use, average age at time of diagnosis of Crohn's disease was 32.3 \u00b1 12.2 years, compared with 43.7 \u00b1 16.3 years for those who had not received biologics (P = 0.005).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20844954", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 865, "text": "Sixty one patients (50.4%) were 20-39 years old and 43 patients (35.5%) were 40 years and older. Colonic involvement was significantly more common (46,5%) in the 40 years and older group compared with 20-39 years group (24.6%) (p = 0.01)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18236809", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 678, "text": "When the age-related incidence of Crohn's disease was plotted for all countries from which such data were available, the peaks of greatest case frequency occurred at ages 15 to 25 years and paralleled a similar peak representing the number of Peyer's patches as a function of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9412954", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 256, "text": "Crohn's disease has a bimodal age distribution of disease onset diagnosis. The peaks (20 and 50 years) may represent different phenotypes or different genetic and/or environmental influences between younger- and older-onset individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8780560", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 1186, "text": "Current therapy for CD in the UK is less likely than previously to involve the use of long-term glucocorticoids.WHAT THIS STUDY ADDS: Despite advances in therapy, short stature and slow growth continue to be encountered in children with CD. There is a need for simple and consistent definitions of growth that can identify poor growth in children with chronic disease.METHODS: The anthropometric and treatment details of 116 children (68 male) with a mean (range) age at diagnosis of 10.8 years (4.9-15.5) and a mean age at maximum follow-up (MF) of 15.4 years (9.4-19.3) were studied retrospectively at diagnosis (T0), at 1 (T1), 2 (T2) and 3 years (T3) after diagnosis and at MF.RESULTS: At T0, mean height SD score (HtSDS) was -0.5 (-3.3 to 2.6) compared to a mid-parental HtSDS of 0.2 (-2.0 to 01.4) (p=0.002). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22685044", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 927, "text": "White patients were significantly more likely to have ileal disease, whereas African American patients were significantly more likely to have ileocolonic and colonic disease. Age at diagnosis younger than 40 years (odds ratio [OR] 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16534420", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1419, "text": "Both age at diagnosis and site of CD involvement were independently associated with expression of ASCA and anti-CBir1.Compared to children 8-15 years of age at diagnosis, those 0-7 years are more likely to express anti-CBir1 but only half as likely to express ASCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19107777", "endSection": "abstract" } ] }, { "body": "How does thyroid hormone affect insulin resistance in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12869545", "http://www.ncbi.nlm.nih.gov/pubmed/20883475", "http://www.ncbi.nlm.nih.gov/pubmed/22031514" ], "ideal_answer": [ "T3 potentiates insulin signaling and improves insulin sensitivity. In addition, T3 lowers blood glucose in a model of type 2 diabetes. TRalpha P398H mutation is associated with insulin resistance. Circulating T(1)AM is produced from thyroid hormones and is found to be increased in diabetic patients." ], "concepts": [ "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007333", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "summary", "id": "51682c52298dcd4e51000067", "snippets": [ { "offsetInBeginSection": 1370, "offsetInEndSection": 1509, "text": "In diabetic vs. nondiabetic patients T(1)AM concentration was significantly increased (0.232 \u00b1 0.014 vs. 0.203 \u00b1 0.006 pmol/ml, P = 0.044),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22031514", "endSection": "sections.0" }, { "offsetInBeginSection": 1678, "offsetInEndSection": 1873, "text": "Our results are consistent with the hypothesis that circulating T(1)AM is produced from thyroid hormones and encourage further investigations on the potential role of T(1)AM in insulin resistance", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22031514", "endSection": "sections.0" }, { "offsetInBeginSection": 98, "offsetInEndSection": 175, "text": "exogenous T3 lowered blood glucose in db/db mice, a model of type 2 diabetes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20883475", "endSection": "sections.0" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1622, "text": "T3 potentiated insulin signaling, improved insulin sensitivity, and increased insulin synthesis, which may contribute to its anti-diabetic effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20883475", "endSection": "sections.0" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1327, "text": "TRalpha P398H mutation is associated with visceral adiposity and insulin resistance", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12869545", "endSection": "sections.0" } ] }, { "body": "Which are the state-of-the-art computational tools for the prediction of gene fusion events?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12519996", "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "http://www.ncbi.nlm.nih.gov/pubmed/11820254", "http://www.ncbi.nlm.nih.gov/pubmed/15701682", "http://www.ncbi.nlm.nih.gov/pubmed/18949021", "http://www.ncbi.nlm.nih.gov/pubmed/21729286", "http://www.ncbi.nlm.nih.gov/pubmed/22250127", "http://www.ncbi.nlm.nih.gov/pubmed/15130848", "http://www.ncbi.nlm.nih.gov/pubmed/15215406", "http://www.ncbi.nlm.nih.gov/pubmed/23236161", "http://www.ncbi.nlm.nih.gov/pubmed/18081932", "http://www.ncbi.nlm.nih.gov/pubmed/17963500", "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "http://www.ncbi.nlm.nih.gov/pubmed/11752322", "http://www.ncbi.nlm.nih.gov/pubmed/21342538", "http://www.ncbi.nlm.nih.gov/pubmed/23365410" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10835131", "o": "Gene Fusion" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0178648", "o": "http://linkedlifedata.com/resource/umls/label/A8396692" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1705736", "o": "http://linkedlifedata.com/resource/umls/label/A10760980" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8396692", "o": "Gene Fusions" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A10760980", "o": "NCI Thesaurus" } ], "ideal_answer": [ "Gene fusion detection - also known as the 'Rosetta Stone' method - involves the identification of fused composite genes in a set of reference genomes, which indicates potential interactions between its un-fused counterpart genes in query genomes. A few methods/tools and computational pipelines for the detection of gene fusion events have been introduced. The basic steps followed in these approaches consist of (i) all-against-all sequence comparison, (ii) detection of non-overlapping similarities of two genes/proteins (components) to a single gene/protein (composite), and optionally (iii) elimination of putative spurious hits (e.g. due to promiscuous domains) achieves via clustering based on sequence similarity and examining dense regions of the resulting graph or by querying the PFAM database. An advantage of gene fusion analysis is that functional associations can be predicted even in cases of genes of unknown function. Due to the computationally intense nature of these approaches, precompiled data of this type are often organized in specialized databases. Tools and databases developed for this purpose include (in alphabetical order): fdfBLAST, FusionDB, InPrePPI, (Integrated method for Prediction of Protein-Protein Interactions), MosaicFinder, Phydbac2, PLEX, Predictome, Rosetta Stone method, STRING." ], "exact_answer": [ [ "fdfBLAST" ], [ "FusionDB" ], [ "InPrePPI", "Integrated method for Prediction of Protein-Protein Interactions" ], [ "MosaicFinder" ], [ "Phydbac2" ], [ "PLEX" ], [ "Predictome" ], [ "Rosetta Stone method" ], [ "STRING" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058977", "http://www.uniprot.org/uniprot/V55_BPT7", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000465", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050939", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003199", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506" ], "type": "list", "id": "5149af96d24251bc05000046", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "MosaicFinder: Identification of fused gene families in sequence similarity networks", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23365410", "endSection": "title" }, { "offsetInBeginSection": 790, "offsetInEndSection": 936, "text": "This leads to an efficient formulation of previous methods of fused gene identification, which we implemented in the Python program FusedTriplets.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23365410", "endSection": "sections.0" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1386, "text": "We implemented this method in the C++ program MosaicFinder, which additionally uses local alignments to discard false positive candidates and indicates potential fusion points.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23365410", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Inference of gene function based on gene fusion events: the rosetta-stone method.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "endSection": "title" }, { "offsetInBeginSection": 106, "offsetInEndSection": 559, "text": "The basic idea is based on the principle of \"guilt by association.\" It is assumed that two proteins, which are found to be transcribed by a single transcript in one (or several) genomes are likely to be functionally linked, for example by acting in a same metabolic pathway or by forming a multiprotein complex. This method is of particular interest for studying genes that exhibit no, or only remote, homologies with already well-characterized proteins", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "endSection": "sections.0" }, { "offsetInBeginSection": 836, "offsetInEndSection": 1058, "text": "This chapter uses the FusionDB database (http://www.igs.cnrs-mrs.fr/FusionDB/) as source of information. FusionDB provides a characterization of a large number of gene fusion events at hand of multiple sequence alignments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025684", "endSection": "sections.0" }, { "offsetInBeginSection": 351, "offsetInEndSection": 468, "text": "PLEX can be searched iteratively and also enables searches for chromosomal gene neighbors and Rosetta Stone linkages.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701682", "endSection": "sections.0" }, { "offsetInBeginSection": 466, "offsetInEndSection": 700, "text": "While phylogenomic profiles remain the central focus of Phydbac2, it now integrates chromosomal proximity and gene fusion analyses as two additional non-similarity-based indicators for inferring pairwise gene functional relationships.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215406", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 437, "text": "Functional links between proteins can often be inferred from genomic associations between the genes that encode them: groups of genes that are required for the same function tend to show similar species coverage, are often located in close proximity on the genome (in prokaryotes), and tend to be involved in gene-fusion events. The database STRING is a precomputed global resource for the exploration and analysis of these associations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12519996", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Protein interaction maps for complete genomes based on gene fusion events", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "endSection": "title" }, { "offsetInBeginSection": 642, "offsetInEndSection": 759, "text": "Here we present a method that identifies gene-fusion events in complete genomes, solely based on sequence comparison.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10573422", "endSection": "sections.0" }, { "offsetInBeginSection": 232, "offsetInEndSection": 570, "text": "Gene fusions have been suggested to be useful characters for identifying evolutionary relationships because they constitute synapomorphies or cladistic characters. To investigate the fidelity of gene-fusion characters, we developed an approach for identifying differentially distributed gene fusions among whole-genome datasets: fdfBLAST.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23236161", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Genome-scale comparative analysis of gene fusions, gene fissions", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23236161", "endSection": "title" }, { "offsetInBeginSection": 604, "offsetInEndSection": 820, "text": "Here we present Predictome, a database of predicted links between the proteins of 44 genomes based on the implementation of three computational methods--chromosomal proximity, phylogenetic profiling and domain fusion", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11752322", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Pairs of genes that function together in a pathway or cellular system can sometimes be found fused together in another organism as a Rosetta Stone protein--a fusion protein whose separate domains are homologous to the two functionally-related proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15130848", "endSection": "sections.0" }, { "offsetInBeginSection": 781, "offsetInEndSection": 995, "text": "Using the Rosetta Stone method and this scoring scheme, we find all significant functional linkages for proteins of E. coli, P. horikshii and S. cerevisiae, and measure the extent of the resulting protein networks.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15130848", "endSection": "sections.0" } ] }, { "body": "Is CHEK2 involved in cell cycle control?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17517688", "http://www.ncbi.nlm.nih.gov/pubmed/16596250", "http://www.ncbi.nlm.nih.gov/pubmed/21956126", "http://www.ncbi.nlm.nih.gov/pubmed/11751432", "http://www.ncbi.nlm.nih.gov/pubmed/23030661", "http://www.ncbi.nlm.nih.gov/pubmed/18024013", "http://www.ncbi.nlm.nih.gov/pubmed/17577921" ], "ideal_answer": [ "CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000075", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071850", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064447", "http://www.uniprot.org/uniprot/CHK2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059565", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031575", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0022402", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051726", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010564", "http://www.uniprot.org/uniprot/CHK2_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007050", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071780", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007049", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002453", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031569", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007346", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059447" ], "type": "yesno", "id": "53175e25b166e2b806000007", "snippets": [ { "offsetInBeginSection": 1904, "offsetInEndSection": 2184, "text": "Moreover, cell-cycle progression genes [i.e. E2F transcription factor (E2F) family and histone deacetylase ( HDAC )] and DNA-repair genes [i.e. growth arrest and DNA-damage-inducible, gamma ( GADD45G ) family and serine/threonine-protein kinase Chk2 ( CHEK2)] were also increased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030661", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 333, "text": "As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21956126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "In the current study, we evaluated the possible associations of seven common variants of the DNA repair and cell cycle control genes BRCA2 and CHEK2 with malignant melanoma (MM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18024013", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 717, "text": "Promotor methylation analysis of key regulatory genes involved in cell cycle control (p14, p15, p16, CHK2), DNA repair (hMLH1), apoptosis (p73, survivin, DAPK), and differentiation (RARb, WT1) was performed by methylation-specific polymerase chain reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17577921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17517688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "High-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been implicated in both of these responses. In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. The fully activated Chk2 then phosphorylates downstream substrates of cell cycle control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16596250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Checkpoint kinase 2 (hCHK2/hCds1) is a tumor suppressor gene involved in cell-cycle control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11751432", "endSection": "abstract" } ] }, { "body": "Describe mechanism of action of PLX3397 drug.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24718867", "http://www.ncbi.nlm.nih.gov/pubmed/24247719", "http://www.ncbi.nlm.nih.gov/pubmed/24583793", "http://www.ncbi.nlm.nih.gov/pubmed/26222558", "http://www.ncbi.nlm.nih.gov/pubmed/25042473", "http://www.ncbi.nlm.nih.gov/pubmed/26156998", "http://www.ncbi.nlm.nih.gov/pubmed/25110953" ], "ideal_answer": [ "PLX3397 works by inhibiting colony-stimulating-factor-1 receptor (CSF1R)." ], "type": "summary", "id": "56c07ef5ef6e394741000023", "snippets": [ { "offsetInBeginSection": 658, "offsetInEndSection": 762, "text": "Following the 25 d lesion, we administered PLX3397, a CSF1R inhibitor, for 30 d to eliminate microglia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26156998", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 429, "text": ".METHODS: Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the autoinhibited conformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222558", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 636, "text": "Treatment with PLX3397, a small molecule inhibitor of the CSF1 receptor CSF1R and related kinases, decreases microglial numbers by promoting microglial apoptosis in both CSF1 overexpressing and control mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25042473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24718867", "endSection": "title" }, { "offsetInBeginSection": 257, "offsetInEndSection": 504, "text": "We hypothesized that PLX3397, which inhibits KIT and colony-stimulating-factor-1 receptor (CSF1R), would be more efficacious than imatinib in GIST by also depleting tumor-associated macrophages, which are generally thought to support tumor growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24583793", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 515, "text": "The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+) myeloid derived suppressor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25110953", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 297, "text": "The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247719", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1145, "text": "In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247719", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 409, "text": "The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247719", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1302, "text": "In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247719", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 298, "text": "The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24247719", "endSection": "abstract" } ] }, { "body": "What disease is small bowel lymphoma commonly associated with", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21532863", "http://www.ncbi.nlm.nih.gov/pubmed/12002682", "http://www.ncbi.nlm.nih.gov/pubmed/2754219", "http://www.ncbi.nlm.nih.gov/pubmed/10912475", "http://www.ncbi.nlm.nih.gov/pubmed/18212211" ], "ideal_answer": [ "Small bowel lymphoma is commonly associated with celiac disease." ], "exact_answer": [ "Celiac disease", "gluten-associated enteropathy", "CELIAC SPRU", "Non tropical spru", "Gluten Sensitive Enteropath" ], "type": "factoid", "id": "5509bd6a1180f13250000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Marginal zone B-cell lymphoma of MALT in small intestine associated with amyloidosis: a rare association.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21532863", "endSection": "title" }, { "offsetInBeginSection": 495, "offsetInEndSection": 654, "text": "This is the first case of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the small intestine associated with amyloidosis in Korea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21532863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "MR enterography of small-bowel lymphoma: potential for suggestion of histologic subtype and the presence of underlying celiac disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18212211", "endSection": "title" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1839, "text": "We describe the characteristics of small-bowel lymphoma on MR enterography, identifying a number of key features that may help the interpreting radiologist in suggesting the underlying histologic subtype and whether the presence of underlying celiac disease is likely.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18212211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Celiac disease is an autoimmune disorder triggered by ingestion of gluten-containing foods. Epidemiologic studies dating from the 1950s established its association with gastrointestinal malignancies, particularly small bowel lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12002682", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 557, "text": "An association between untreated coeliac disease and intestinal malignancy is well described so it is possible that patients with undiagnosed coeliac disease constitute a significant reservoir of preventable gastrointestinal malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10912475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "An increased incidence of small bowel lymphoma in patients with long-standing celiac sprue is well documented in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2754219", "endSection": "abstract" } ] }, { "body": "Are the proteins Erbin (LAP2) and Merlin cooperating?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15659388", "http://www.ncbi.nlm.nih.gov/pubmed/19289088" ], "ideal_answer": [ "Yes, Erbin and Merlin are cooperating." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/MERL_RAT", "http://www.uniprot.org/uniprot/MERL_PAPAN", "http://www.uniprot.org/uniprot/MERL_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025581", "http://www.uniprot.org/uniprot/LAP2_HUMAN", "http://www.biosemantics.org/jochem#4267552" ], "type": "yesno", "id": "530c7fa4970c65fa6b000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289088", "endSection": "title" }, { "offsetInBeginSection": 451, "offsetInEndSection": 646, "text": "The results show that the epithelial-enriched protein Erbin controls the function of the NF2 tumor suppressor Merlin by determining the output of Merlin's physical interactions with active PAK2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289088", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1063, "text": "Erbin controls Merlin tumor suppressor function by switching the functional valence of PAK2 binding", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289088", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by a monoclonal antibody Secukinumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24157091", "http://www.ncbi.nlm.nih.gov/pubmed/22595313", "http://www.ncbi.nlm.nih.gov/pubmed/23730881", "http://www.ncbi.nlm.nih.gov/pubmed/25132411", "http://www.ncbi.nlm.nih.gov/pubmed/23858337", "http://www.ncbi.nlm.nih.gov/pubmed/22875601", "http://www.ncbi.nlm.nih.gov/pubmed/25268669", "http://www.ncbi.nlm.nih.gov/pubmed/23253932", "http://www.ncbi.nlm.nih.gov/pubmed/23998727", "http://www.ncbi.nlm.nih.gov/pubmed/22280236", "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "http://www.ncbi.nlm.nih.gov/pubmed/25007392", "http://www.ncbi.nlm.nih.gov/pubmed/24677511", "http://www.ncbi.nlm.nih.gov/pubmed/24979544", "http://www.ncbi.nlm.nih.gov/pubmed/25484038", "http://www.ncbi.nlm.nih.gov/pubmed/25398488", "http://www.ncbi.nlm.nih.gov/pubmed/24452484", "http://www.ncbi.nlm.nih.gov/pubmed/23106107", "http://www.ncbi.nlm.nih.gov/pubmed/23834907", "http://www.ncbi.nlm.nih.gov/pubmed/25243910", "http://www.ncbi.nlm.nih.gov/pubmed/24035250", "http://www.ncbi.nlm.nih.gov/pubmed/25354738", "http://www.ncbi.nlm.nih.gov/pubmed/24354461", "http://www.ncbi.nlm.nih.gov/pubmed/23361084", "http://www.ncbi.nlm.nih.gov/pubmed/24827753", "http://www.ncbi.nlm.nih.gov/pubmed/23290985" ], "ideal_answer": [ "Secukinumab (AIN457) is a fully human anti-interleukin-17A monoclonal antibody that neutralizes interleukin-17A." ], "exact_answer": [ "interleukin-17A" ], "type": "factoid", "id": "54e0d7471388e8454a000015", "snippets": [ { "offsetInBeginSection": 670, "offsetInEndSection": 993, "text": "We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25484038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Secukinumab, a fully human anti-IL-17A monoclonal antibody, neutralizes IL-17A, a key cytokine in the pathogenesis of psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25354738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "BACKGROUND: Secukinumab is a fully human anti-interleukin-17A monoclonal antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25243910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, demonstrated efficacy and safety in moderate-to-severe plaque psoriasis when administered via subcutaneous injection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25132411", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 226, "text": "We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25007392", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 1177, "text": "Ustekinumab (a monoclonal antibody directed against the common p40 subunit of IL-23 and IL-12), secukinumab, ixekizumab (both monoclonal antibodies directed against IL-17A), and brodalumab a monoclonal antibody against the IL-17RA receptor) have been recently used in proof-of-concept and randomized trials in the ankylosing spondylitis and/or psoriatic arthritis subforms of SpA, with overall very promising clinical efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24827753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates IL17A-induced levels of IL6 in human astrocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24677511", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "The family of interleukin 17 receptors (IL17Rs), subtypes IL17RA-IL17RE, is targeted by the group of pro-inflammatory IL17 cytokines (IL17A-F) and moreover the newly developed anti-IL17A antibody secukinumab (AIN457) has shown promise in Phase II trials in multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24677511", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1628, "text": " Three agents neutralizing IL-17 (i.e., secukinumab and ixekizumab) or antagonizing its receptor (i.e., brodalumab) are currently being tested for efficacy and safety in the treatment of plaque psoriasis and PsA. Secukinumab is a fully human IgG1 monoclonal antibody that selectively binds and neutralizes IL-17A whose efficacy in the therapy of chronic plaque psoriasis has been demonstrated in different phase II clinical trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24452484", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 913, "text": "Associations between IGA 0/1 responder rates and PASI scores were evaluated using data from two phase 2 studies with the anti-interleukin (IL)-17A monoclonal antibody secukinumab (AIN457) that utilized a similar 6-point IGA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24354461", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1249, "text": " Several IL-17A inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibodies, secukinumab and ixekizumab, and the anti-17RA monoclonal antibody brodalumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035250", "endSection": "title" }, { "offsetInBeginSection": 336, "offsetInEndSection": 480, "text": "We assessed the efficacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035250", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 445, "text": "In a proof-of-concept study for the treatment of patients with Crohn's disease, secukinumab, a monoclonal antibody directed against IL-17A, was ineffective and associated with more adverse events than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23998727", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 898, "text": "Several IL-17A blockers, including the anti-IL-17A monoclonal antibodies secukinumab and ixekizumab, and the anti-IL-17 receptor subunit A monoclonal antibody brodalumab have been evaluated in phase II clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23858337", "endSection": "abstract" }, { "offsetInBeginSection": 1238, "offsetInEndSection": 1426, "text": "Further studies are needed to clarify whether the therapeutic blockade of IL-17A through the anti-IL-17A monoclonal antibody secukinumab is able to counteract the fibrogenic process in CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23834907", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 339, "text": "Th-17A antagonism has been investigated by a randomized controlled trial in PsA patients with secukinumab, a fully human, high-affinity, monoclonal antibody in a cohort of patients with active PsA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23730881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23361084", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "OBJECTIVE: To evaluate the efficacy and safety of secukinumab, a fully human, anti-interleukin (IL)-17A monoclonal antibody, in patients with psoriatic arthritis (PsA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23361084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "PURPOSE: To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23290985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Effect of IL-17A blockade with secukinumab in autoimmune diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23253932", "endSection": "title" }, { "offsetInBeginSection": 797, "offsetInEndSection": 1062, "text": "Early clinical data are now available on secukinumab (AIN457), a recombinant, highly selective, fully human monoclonal anti-IL-17A antibody of the IgG1/\u03ba isotype, enabling a preliminary assessment of the effects of IL-17A inhibition in multiple autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23253932", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1607, "text": "In conjunction with studies using the humanised anti-IL-17A monoclonal antibody (mAb) ixekizumab (LY2439821) and the fully human anti-IL-17RA mAb brodalumab (AMG 827), the findings on secukinumab provide evidence for the role of IL-17A in the pathophysiology of autoimmune disease and suggest the potential value of targeting this cytokine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23253932", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 673, "text": "OBJECTIVES: To assess the efficacy and safety of different doses of secukinumab, a fully human anti-IL-17A IgG1\u03ba monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23106107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Treatment with the interleukin-17A-blocking antibody secukinumab does not interfere with the efficacy of influenza and meningococcal vaccinations in healthy subjects: results of an open-label, parallel-group, randomized single-center study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22875601", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Our objective was to evaluate the efficacy of influenza and meningococcal vaccinations in healthy subjects exposed to the anti-interleukin-17A (IL-17A) monoclonal antibody (MAb) secukinumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22875601", "endSection": "abstract" }, { "offsetInBeginSection": 1595, "offsetInEndSection": 1778, "text": "Blockade of IL-17A by secukinumab does not appear to interfere with efficacy of influenza and meningococcal vaccinations, as assessed by the achievement of protective antibody levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22875601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22595313", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "OBJECTIVE: The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22595313", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1365, "text": "Secukinumab is an IL-17A monoclonal antibody that is under development and preliminary results have suggested its efficacy in inflammatory mediated diseases such as psoriasis and ankylosing spondylitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22280236", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1200, "text": "Promising recent Phase II results on the anti-IL-17A antibody secukinumab (AIN457) are outlined and a short update on tabalumab (LY2127399) is given", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1209, "text": "Several IL-17A inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibodies, secukinumab and ixekizumab, and the anti-17RA monoclonal antibody brodalumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157091", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 896, "text": "Several IL-17A blockers, including the anti-IL-17A monoclonal antibodies secukinumab and ixekizumab, and the anti-IL-17 receptor subunit A monoclonal antibody brodalumab have been evaluated in phase II clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23858337", "endSection": "abstract" } ] }, { "body": "Which calcium/calmodulin dependent protein phosphatase is involved in the activation of the family of NFAT transcription factors (Nuclear Factors of Activated T cells)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17572487", "http://www.ncbi.nlm.nih.gov/pubmed/10593895", "http://www.ncbi.nlm.nih.gov/pubmed/17099778", "http://www.ncbi.nlm.nih.gov/pubmed/9374467", "http://www.ncbi.nlm.nih.gov/pubmed/16260608", "http://www.ncbi.nlm.nih.gov/pubmed/18005668", "http://www.ncbi.nlm.nih.gov/pubmed/9727000", "http://www.ncbi.nlm.nih.gov/pubmed/16229015", "http://www.ncbi.nlm.nih.gov/pubmed/14729474", "http://www.ncbi.nlm.nih.gov/pubmed/11559828", "http://www.ncbi.nlm.nih.gov/pubmed/11592964" ], "ideal_answer": [ "The activity of NFAT proteins is tightly regulated by the Ca(2+)/calmodulin-dependent protein phosphatase 2B/calcineurin (CaN).Dephosphorylation of NFAT by CaN is required for NFAT nuclear localization." ], "exact_answer": [ "Calcineurin", "CaN", "phosphatase 2b" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050778", "http://www.uniprot.org/uniprot/CALM_ELEEL" ], "type": "factoid", "id": "54f9c40ddd3fc62544000001", "snippets": [ { "offsetInBeginSection": 692, "offsetInEndSection": 1027, "text": "Transcription downstream of Ca(2+) influx is in large part funneled through the transcription factor nuclear factor of activated T cells (NFAT), a heavily phosphorylated protein that is cytoplasmic in resting cells, but that enters the nucleus when dephosphorylated by the calmodulin-dependent serine/threonine phosphatase calcineurin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17572487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 611, "text": "Calcineurin signaling has been implicated in a broad spectrum of developmental processes in a variety of organ systems. Calcineurin is a calmodulin-dependent, calcium-activated protein phosphatase composed of catalytic and regulatory subunits. The serine/threonine-specific phosphatase functions within a signal transduction pathway that regulates gene expression and biological responses in many developmentally important cell types. Calcineurin signaling was first defined in T lymphocytes as a regulator of nuclear factor of activated T cells (NFAT) transcription factor nuclear translocation and activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14729474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "NFAT (nuclear factor of activated T cell) proteins are expressed in most immune system cells and regulate the transcription of cytokine genes critical for the immune response. The activity of NFAT proteins is tightly regulated by the Ca(2+)/calmodulin-dependent protein phosphatase 2B/calcineurin (CaN). Dephosphorylation of NFAT by CaN is required for NFAT nuclear localization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11592964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 405, "text": "Calcium activated gene transcription through Nuclear Factor of Activated T-cells, (NFAT) proteins, is emerging as a ubiquitous mechanism for the control of important physiological processes. Of the five mammalian NFAT isoforms, transcriptional activities of NFATs 1-4 are stimulated by a calcium driven association between the ubiquitous phosphatase calcineurin and the calcium-sensing protein calmodulin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18005668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 503, "text": "Transcription factors of the NFAT (nuclear factor of activated T cells) family are expressed in most immune system cells and in a range of other cell types. Signaling through NFAT is implicated in the regulation of transcription for the immune response and other processes, including differentiation and apoptosis. NFAT normally resides in the cytoplasm, and a key aspect of the NFAT activation pathway is the regulation of its nuclear import by the Ca(2+)/calmodulin-dependent phosphatase calcineurin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11559828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "The nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells. NFAT activation is mediated in part by induced nuclear import. This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9374467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "The calcium-regulated protein phosphatase calcineurin (PP2B) functions as a regulator of gene expression in diverse tissues through the dephosphorylation and activation of a family of transcription factors known as nuclear factor of activated T cells (NFAT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16260608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Calcineurin, a Ca(2+)/calmodulin-stimulated protein phosphatase, plays a key role in T-cell activation by regulating the activity of NFAT (nuclear factor of activated T cells), a family of transcription factors required for the synthesis of several cytokine genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10593895", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 545, "text": "The calcium/calmodulin-dependent phosphatase calcineurin, which signals to nuclear factor of activated T cells (NFAT) transcription factors, serves as a transducer of calcium signals and is sufficient and necessary for pathologic cardiac hypertrophy and remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17099778", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1560, "text": "Upon activation, Cn directly binds to, and dephosphorylates nuclear factor of activated T cells (NFAT) transcription factors within the cytoplasm allowing them to translocate to the nucleus and participate in the regulation of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16229015", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 305, "text": "The functions of NFAT proteins are directly controlled by the calcium- and calmodulin-dependent phosphatase calcineurin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9727000", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 1026, "text": "Transcription downstream of Ca(2+) influx is in large part funneled through the transcription factor nuclear factor of activated T cells (NFAT), a heavily phosphorylated protein that is cytoplasmic in resting cells, but that enters the nucleus when dephosphorylated by the calmodulin-dependent serine/threonine phosphatase calcineurin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17572487", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 302, "text": "The activity of NFAT proteins is tightly regulated by the Ca(2+)/calmodulin-dependent protein phosphatase 2B/calcineurin (CaN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11592964", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 304, "text": "The functions of NFAT proteins are directly controlled by the calcium- and calmodulin-dependent phosphatase calcineurin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9727000", "endSection": "abstract" } ] }, { "body": "Is abdominal pain a common symptom in autism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22997101", "http://www.ncbi.nlm.nih.gov/pubmed/21415091", "http://www.ncbi.nlm.nih.gov/pubmed/21114016", "http://www.ncbi.nlm.nih.gov/pubmed/23371507", "http://www.ncbi.nlm.nih.gov/pubmed/12846385", "http://www.ncbi.nlm.nih.gov/pubmed/19329445", "http://www.ncbi.nlm.nih.gov/pubmed/14523189", "http://www.ncbi.nlm.nih.gov/pubmed/22850932" ], "ideal_answer": [ "Yes, although there are no precise data. There is data that Lactase deficiency, not associated with intestinal inflammation or injury, is common in autistic children and may contribute to abdominal discomfort, pain and observed aberrant behavior." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015746", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321" ], "type": "yesno", "id": "515debe7298dcd4e51000026", "snippets": [ { "offsetInBeginSection": 222, "offsetInEndSection": 381, "text": "Participants included 132 children with ASD and 81 with special educational needs (SEN) but no ASD, aged 10-14\u00a0years plus 82 typically developing (TD) children", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371507", "endSection": "sections.0" }, { "offsetInBeginSection": 807, "offsetInEndSection": 946, "text": "The ASD group had significantly increased past vomiting and diarrhoea compared with the TD group and more abdominal pain than the SEN group", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371507", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Many children with autism spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22997101", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Children with autism spectrum disorders (ASD) experience high rates of anxiety, sensory processing problems, and gastrointestinal (GI) problems", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850932", "endSection": "sections.0" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1142, "text": "The results indicate that anxiety, sensory over-responsivity and GI problems are possibly interrelated phenomenon for children with ASD, and may have common underlying mechanisms.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850932", "endSection": "sections.0" }, { "offsetInBeginSection": 699, "offsetInEndSection": 883, "text": "Lactase deficiency not associated with intestinal inflammation or injury is common in autistic children and may contribute to abdominal discomfort, pain and observed aberrant behavior.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415091", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Autistic behavior is often accompanied by numerous disturbing symptoms on the part of gastrointestinal system, such as abdominal pain, constipation or diarrhea.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21114016", "endSection": "sections.0" }, { "offsetInBeginSection": 152, "offsetInEndSection": 386, "text": "Information on children's stool patterns and gut symptoms collected by questionnaire at 4 weeks and at 6, 18, 30 and 42 months of age were available for 12,984 children from the Avon Longitudinal Study of Parents and Children (ALSPAC)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329445", "endSection": "sections.0" }, { "offsetInBeginSection": 583, "offsetInEndSection": 794, "text": "Comparison of the ASD and control group during the first 3.5 years of life showed no major differences in stool colour or consistency, or in frequency of diarrhoea, constipation, bloody stools or abdominal pain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329445", "endSection": "sections.0" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 2032, "text": "Constipation is a frequent finding in children with gastrointestinal symptoms and autism, particularly in the rectosigmoid colon, often with acquired megarectum. The absence of any correlation between the clinical history and the degree of fecal impaction in autistic children confirms the importance of an abdominal radiograph in the assessment of their degree of constipation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14523189", "endSection": "sections.0" }, { "offsetInBeginSection": 311, "offsetInEndSection": 590, "text": "In a sample of 137 children, age 24-96 months, classified as having autism or ASD by the Autism Diagnostic Observation Schedule-Generic, 24 percent had a history of at least one chronic gastrointestinal symptom. The most common symptom was diarrhea, which occurred in 17 percent.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12846385", "endSection": "sections.0" } ] }, { "body": "Are cyclophilins ubiquitously expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19403925", "http://www.ncbi.nlm.nih.gov/pubmed/15869639", "http://www.ncbi.nlm.nih.gov/pubmed/25259854", "http://www.ncbi.nlm.nih.gov/pubmed/23849880", "http://www.ncbi.nlm.nih.gov/pubmed/14568539", "http://www.ncbi.nlm.nih.gov/pubmed/24887548", "http://www.ncbi.nlm.nih.gov/pubmed/16928193", "http://www.ncbi.nlm.nih.gov/pubmed/23123451", "http://www.ncbi.nlm.nih.gov/pubmed/15735342", "http://www.ncbi.nlm.nih.gov/pubmed/21087465", "http://www.ncbi.nlm.nih.gov/pubmed/19923714", "http://www.ncbi.nlm.nih.gov/pubmed/17103061", "http://www.ncbi.nlm.nih.gov/pubmed/15935056" ], "ideal_answer": [ "Yes, \tcyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily." ], "exact_answer": "yes", "type": "yesno", "id": "56f6ab7009dd18d46b00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Cyclophilin from Leishmania donovani (LdCyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24887548", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 417, "text": "Cyclophilins (CYPs) and FK506-binding proteins (FKBPs) are ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25259854", "endSection": "abstract" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1553, "text": " However, their wide distribution and ubiquitous nature signifies their fundamental importance in plant survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23123451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23849880", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 296, "text": "FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21087465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Cyclophilin is a ubiquitous peptidyl prolyl cis/trans isomerase that plays critical roles in many biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19403925", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 448, "text": "The receptor for cyclosporin is the protein cyclophilin, which is a ubiquitous peptidylprolyl isomerase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19923714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16928193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Cyclophilins are folding helper enzymes belonging to the class of peptidyl-prolyl cis-trans isomerases (PPIases; EC 5.2.1.8) that catalyze the cis-trans isomerization of peptidyl-prolyl bonds in proteins. They are ubiquitous proteins present in almost all living organisms analyzed to date, with extremely rare exceptions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Immunophilins are ubiquitous enzymes responsible for proline isomerisation during protein synthesis and for the chaperoning of several membrane proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15935056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl-prolyl cis-trans isomerases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15735342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Cyclophilins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases), which are ubiquitous and highly conserved enzymes capable of cis/trans isomerizing Xaa-Pro peptide bonds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14568539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Originally identified as the cellular targets of immunosuppressant drugs, the immunophilins encompass two ubiquitous protein families: the FK-506 binding proteins or FKBPs, and the cyclosporin-binding proteins or cyclophilins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15869639", "endSection": "abstract" } ] }, { "body": "Are adenylyl cyclases always transmembrane proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25010002", "http://www.ncbi.nlm.nih.gov/pubmed/24980705", "http://www.ncbi.nlm.nih.gov/pubmed/25073090", "http://www.ncbi.nlm.nih.gov/pubmed/25009261", "http://www.ncbi.nlm.nih.gov/pubmed/25350397", "http://www.ncbi.nlm.nih.gov/pubmed/24574382", "http://www.ncbi.nlm.nih.gov/pubmed/25066614", "http://www.ncbi.nlm.nih.gov/pubmed/25064589", "http://www.ncbi.nlm.nih.gov/pubmed/25220136" ], "ideal_answer": [ "Adenylyl cyclases exists both as transmembrane and soluble proteins." ], "exact_answer": "no", "type": "yesno", "id": "56e5aeec0c19e5451d000002", "snippets": [ { "offsetInBeginSection": 35, "offsetInEndSection": 64, "text": "ransmembrane adenylyl cyclase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25350397", "endSection": "title" }, { "offsetInBeginSection": 829, "offsetInEndSection": 889, "text": " Transmembrane adenylyl cyclase (tmAC) and soluble AC (sAC) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25220136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24574382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 25, "text": "Soluble adenylyl cyclase ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25009261", "endSection": "title" }, { "offsetInBeginSection": 608, "offsetInEndSection": 685, "text": "transmembrane adenylyl cyclases (tmACs), and soluble adenylyl cyclase (sAC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25009261", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 306, "text": " Here, we showed that both transmembrane AC (tmAC) and soluble AC (sAC) are distinctly involved in the regulation of sperm motility in the ascidian Ciona intestinalis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25073090", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 874, "text": "cAMP production in beta cells is mediated not simply by transmembrane adenylyl cyclases (TMACs), but also by sAC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980705", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 634, "text": "In contrast to tmAC, sAC produces cAMP in various intracellular microdomains close to specific cAMP targets, e.g., in nucleus and mitochondria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25010002", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 703, "text": "soluble adenylyl cyclase (sAC, ADCY10), the ubiquitous, non-transmembrane adenylyl cyclase, was found to play a key role in neuronal survival and axon growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25064589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Central role of soluble adenylyl cyclase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066614", "endSection": "title" } ] }, { "body": "What histone trimethylation has been associated to RNA splicing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23740743", "http://www.ncbi.nlm.nih.gov/pubmed/18042460", "http://www.ncbi.nlm.nih.gov/pubmed/22308494", "http://www.ncbi.nlm.nih.gov/pubmed/21807997", "http://www.ncbi.nlm.nih.gov/pubmed/23676078", "http://www.ncbi.nlm.nih.gov/pubmed/19823040", "http://www.ncbi.nlm.nih.gov/pubmed/22188810", "http://www.ncbi.nlm.nih.gov/pubmed/21792193" ], "ideal_answer": [ "Mostly H3K36me3 but there is some evidence that H3K4me3 may also play a role in splicing" ], "exact_answer": [ "H3K36me3" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010452", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2001253", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016571", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097198" ], "type": "factoid", "id": "532ff917d6d3ac6a34000038", "snippets": [ { "offsetInBeginSection": 1031, "offsetInEndSection": 1236, "text": "histone H3 lysine 36 tri-methylation (H3K36Me3), exhibits different patterns around the cleavage sites of genes using multiple polyadenylation sites from those of genes using a single polyadenylation site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23740743", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1439, "text": "ChIP-sequencing data mapped onto skipped exon events reveal a correlation between histone H3K36 trimethylation peaks and skipped exons, suggesting epigenetic marks being part of alternative splicing regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23676078", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1290, "text": "Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 trimethylation, consistent with the role of histone modifications at alternatively spliced sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22308494", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1182, "text": "H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22188810", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 300, "text": "We investigated whether a causal relationship exists between splicing and chromatin modification by asking whether splice-site mutations affect the methylation of histone H3K36", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21807997", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 158, "text": " splicing can also contribute to histone modification,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21792193", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 452, "text": "Genome-wide analysis of histone methylation in human cell lines and mouse primary T cells reveals that intron-containing genes are preferentially marked with histone H3 Lys36 trimethylation (H3K36me3) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21792193", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 442, "text": " transcription and splicing are functionally intertwined, and that modified nucleosomes with trimethylation of lysine 36 in histone subunit 3 (H3K36me3) are enriched at internal exons and the downstream flanking intronic regions of highly expressed genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19823040", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1062, "text": "methylated H3K4 serves to facilitate the competency of pre-mRNA maturation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18042460", "endSection": "abstract" } ] }, { "body": "What was the purpose of the FANTOM4 project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19377474", "http://www.ncbi.nlm.nih.gov/pubmed/19374775", "http://www.ncbi.nlm.nih.gov/pubmed/21075797" ], "ideal_answer": [ "The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments." ], "exact_answer": [ "Better understand the transcriptional network that regulates macrophage differentiation" ], "type": "factoid", "id": "569e7721ceceede94d000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21075797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21075797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19377474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21075797", "endSection": "abstract" } ] }, { "body": "Does low T3 negatively affect prognosis of patients after cardiac surgery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12475369", "http://www.ncbi.nlm.nih.gov/pubmed/4057698", "http://www.ncbi.nlm.nih.gov/pubmed/2627465", "http://www.ncbi.nlm.nih.gov/pubmed/12165116", "http://www.ncbi.nlm.nih.gov/pubmed/14500064", "http://www.ncbi.nlm.nih.gov/pubmed/19448543", "http://www.ncbi.nlm.nih.gov/pubmed/23958074", "http://www.ncbi.nlm.nih.gov/pubmed/9078538", "http://www.ncbi.nlm.nih.gov/pubmed/15868525", "http://www.ncbi.nlm.nih.gov/pubmed/21248453", "http://www.ncbi.nlm.nih.gov/pubmed/16719939" ], "ideal_answer": [ "Low cardiac output syndrome after cardiac surgery for congenital heart diseases is associated with decreased T3\nLow T3 concentrations are associated with occurrence of post operative atrial fibrillation\nLow T3 concentrations are inversely correlated with the days of post operative hospitalization" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013903", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002303", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005067" ], "type": "yesno", "id": "53302bced6d3ac6a34000039", "snippets": [ { "offsetInBeginSection": 1819, "offsetInEndSection": 2049, "text": "ur findings suggest that the development of LCOS after congenital heart surgery is associated with decreased total and free T3, and increased IL-8 levels at 48 hours, and preoperative tT4 level is an independent predictor of LCOS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21248453", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1575, "text": "Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500064", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1295, "text": "A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12475369", "endSection": "abstract" } ] }, { "body": "Which deficiency is the cause of restless leg syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11310286", "http://www.ncbi.nlm.nih.gov/pubmed/19935988", "http://www.ncbi.nlm.nih.gov/pubmed/8363978", "http://www.ncbi.nlm.nih.gov/pubmed/18360657", "http://www.ncbi.nlm.nih.gov/pubmed/12530992", "http://www.ncbi.nlm.nih.gov/pubmed/22377249", "http://www.ncbi.nlm.nih.gov/pubmed/21358851", "http://www.ncbi.nlm.nih.gov/pubmed/21211209", "http://www.ncbi.nlm.nih.gov/pubmed/19467991", "http://www.ncbi.nlm.nih.gov/pubmed/16982219", "http://www.ncbi.nlm.nih.gov/pubmed/19039990", "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "http://www.ncbi.nlm.nih.gov/pubmed/19081645", "http://www.ncbi.nlm.nih.gov/pubmed/20814842", "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "http://www.ncbi.nlm.nih.gov/pubmed/20598107" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050425", "o": "MSH:D012148" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050425", "o": "restless legs syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:0050425", "o": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:331" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:331", "o": "central nervous system disease" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11938025", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1837285", "o": "http://linkedlifedata.com/resource/umls/label/A11938025" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11938025", "o": "RESTLESS LEGS SYNDROME, SUSCEPTIBILITY TO, 2" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11966695", "o": "RLS2" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1837285", "o": "http://linkedlifedata.com/resource/umls/label/A11966695" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1837285", "o": "http://linkedlifedata.com/resource/umls/label/A11938025" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11966695", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11938025", "o": "608831" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11966695", "o": "608831" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17462703", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17466336", "o": "RESTLESS LEGS SYNDROME, SUSCEPTIBILITY TO, 7" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17462703", "o": "RLS7" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2748506", "o": "http://linkedlifedata.com/resource/umls/label/A17462703" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2748506", "o": "http://linkedlifedata.com/resource/umls/label/A17466336" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17466336", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17462703", "o": "612853" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17466336", "o": "612853" } ], "ideal_answer": [ "Iron deficiency (low serum ferritin) is a recognized cause for RLS. Further, in the striatum of subjects with restless legs syndrome, the dopamine transporter is decreased, which leads to impaired dopaminergic neurotransmission. There is also a report of magnesium deficiency underlying RLS." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012148" ], "type": "summary", "id": "52f89a002059c6d71c00004c", "snippets": [ { "offsetInBeginSection": 914, "offsetInEndSection": 1003, "text": "Homozygosity for the T-allele of BTBD9 rs9296249 was associated with lower serum ferritin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1371, "text": "This polymorphism has previously been associated with RLS, but not low iron stores in blood donors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 476, "text": "Iron deficiency is a common cause of anemia in patients with end stage renal disease (ESRD). Intravenous iron administration, especially in those requiring treatment with erythropoiesis stimulating agents (ESA) is an essential component of the management of anemia in ESRD patients. Iron improves hemoglobin, reduces ESA dose requirement and also has nonerythropoietic effects including improvement in physical performance, cognition and amelioration of restless leg syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22377249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358851", "endSection": "title" }, { "offsetInBeginSection": 868, "offsetInEndSection": 990, "text": "RLS subjects had significantly lower DAT binding in the striatum compared to controls on both the Day and the Night scans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358851", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1030, "text": "Secondary RLS is a complication of PD. Deficiency of iron and decreased inhibition function of spinal cord may lead to the occurrence of RLS in PD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211209", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 690, "text": "Association of iron deficiency with febrile seizures, pica, breath holding spells, restless leg syndrome and thrombosis is increasingly being recognized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20814842", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 310, "text": "Iron depletion is common in regular blood donors. The objective of the study was to investigate the frequency and severity of iron depletion in regular blood donors and whether IV iron is more effective than oral to avoid iron depletion and symptoms thereof, especially restless legs syndrome (RLS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598107", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1295, "text": "Iron status is poor in regular blood donors, restless legs syndrome is common,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598107", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1365, "text": "Furthermore, there appears to be an association between iron deficiency and those suffering from Restless Leg Syndrome (RLS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19935988", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 209, "text": "Clinical studies have implicated the dopaminergic system in RLS, while others have suggested that it is associated with insufficient levels of brain iron", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19467991", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 119, "text": " Iron deficiency is associated with paediatric sleep disturbances; in particular, restless leg syndrome (RLS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19081645", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 957, "text": "Here we described seven pediatric RLS patients. All of the parents of our patients had difficult times to make their children sleep due to irritability, restlessness, and demanding bedtime routines. All patients had asked their parents to rub their feet in bed, and it took more than half an hour to soothe them until they fell asleep. Their mothers had been exhausted from this night-time routine. However, they did not consider the routine abnormal, as it had been their habitual behavior since infancy. Some parents were too distressed or embarrassed to describe the symptoms of their child properly. Five patients had clear family history and none had obvious periodic leg movements during sleep. All patients showed low levels of ferritin and iron supplementation was effective in five cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19039990", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 608, "text": "RLS may also be secondary to a number of conditions including iron deficiency, pregnancy and end-stage renal failure and, perhaps, neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18360657", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 860, "text": "The pathogenesis of RLS probably involves the interplay of systemic or brain iron deficiency and impaired dopaminergic neurotransmission in the subcortex of the brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18360657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Restless leg syndrome manifested by iron deficiency from chronic hemoptysis in cystic fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982219", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Restless leg syndrome (RLS) and periodic limb movement disorder (PLMD) are considered to be a continuum of a neurological sleep disorder associated with abnormal iron metabolism or deficiency. I describe a case of RLS and PLMD in a cystic fibrosis patient with iron deficiency from chronic hemoptysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982219", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 974, "text": "Iron deficiency in the central nervous system is known to cause motor impairment and cognitive deficits; more recently, it has been suggested that it may play a role in the pathophysiology of the restless leg syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12530992", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 662, "text": "The syndrome is increasingly often diagnosed, particularly in association with iron deficiency, during pregnancy, in chronic renal failure and in patients with peripheral neuropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11310286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8363978", "endSection": "title" } ] }, { "body": "List the results of mutated casein kinase 1 epsilon. ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18522517", "http://www.ncbi.nlm.nih.gov/pubmed/11076012", "http://www.ncbi.nlm.nih.gov/pubmed/20507565", "http://www.ncbi.nlm.nih.gov/pubmed/19142762", "http://www.ncbi.nlm.nih.gov/pubmed/24744456" ], "ideal_answer": [ "Mutation in casein kinase 1 epsilon results in a short circadian period, abnormal entrainment to light cycles, and potentiated resetting responses to light.\nMutations of CK1epsilon found in breast cancer can suppress Wnt/beta-catenin as well as promote the Wnt/Rac-1/JNK and Wnt/NFAT pathways, thus contributing to breast cancer development via effects on cell adhesion and migration.\nCsnk1e is regulating not only the timing of sleep, but also the REM sleep amount and NREM sleep architecture." ], "exact_answer": [ [ "short circadian period" ], [ "abnormal entrainment to light cycles" ], [ "potentiated resetting responses to light" ], [ "REM sleep amount" ], [ "NREM sleep architecture" ], [ "effects on cell adhesion" ], [ "effects on cell migration" ], [ "timing of sleep" ] ], "type": "list", "id": "56e460d051531f7e33000019", "snippets": [ { "offsetInBeginSection": 1461, "offsetInEndSection": 1678, "text": "These results demonstrate a role for Csnk1e in regulating not only the timing of sleep, but also the REM sleep amount and NREM sleep architecture, and support Csnk1e as a causal gene in the sleep QTL on chromosome 15.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24744456", "endSection": "abstract" }, { "offsetInBeginSection": 1812, "offsetInEndSection": 2038, "text": "mutations of CK1epsilon found in breast cancer can suppress Wnt/beta-catenin as well as promote the Wnt/Rac-1/JNK and Wnt/NFAT pathways, thus contributing to breast cancer development via effects on cell adhesion and migration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20507565", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 410, "text": "results in a short circadian period, abnormal entrainment to light cycles, and potentiated resetting responses to light.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19142762", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 677, "text": "We now demonstrate that the mutation results in a heightened sensitivity to light, suggesting that CK1epsilon also regulates the photic entrainment pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19142762", "endSection": "abstract" } ] }, { "body": "Does neuroglobin has neuroprotective properties in the setting of traumatic brain injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23658829", "http://www.ncbi.nlm.nih.gov/pubmed/24491879", "http://www.ncbi.nlm.nih.gov/pubmed/20345238", "http://www.ncbi.nlm.nih.gov/pubmed/20476562", "http://www.ncbi.nlm.nih.gov/pubmed/20544857", "http://www.ncbi.nlm.nih.gov/pubmed/25624825", "http://www.ncbi.nlm.nih.gov/pubmed/21915648", "http://www.ncbi.nlm.nih.gov/pubmed/22703519", "http://www.ncbi.nlm.nih.gov/pubmed/22664218", "http://www.ncbi.nlm.nih.gov/pubmed/24642455" ], "ideal_answer": [ "Yes, neuroglobin has neuroprotective properties in the setting of traumatic brain injury." ], "exact_answer": "yes", "type": "yesno", "id": "56c1d846ef6e39474100002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20345238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Neuroglobin (Ngb) is proposed to be a neuron-specific, hypoxia-responsive, neuroprotective protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20544857", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1081, "text": "CONCLUSION: The increased expression of neuroglobin in traumatic brain injury informed us that neuroglobin had anti-apoptosis action in post-injury neuron. It could protect the neuron from traumatic stress and secondary ischemia and hypoxia insults during ultra-early and acute stages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20476562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Neuroglobin-overexpression reduces traumatic brain lesion size in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22703519", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22703519", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1201, "text": "CONCLUSION: Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22703519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Neuroglobin upregulation offers neuroprotection in traumatic brain injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664218", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "OBJECTIVES: The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664218", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1060, "text": "CONCLUSIONS: NGB was upregulated in TBI and overexpressed rNGB had a significant neuroprotection in TBI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664218", "endSection": "abstract" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1189, "text": "This study suggested that rNGB overexpression may be a new strategy for treating of TBI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20345238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22703519", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 334, "text": "Various studies seem to indicate that neuroglobin is a neuroprotective agent when overexpressed, acting as a potent inhibitor of oxidative and nitrosative stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24491879", "endSection": "abstract" } ] }, { "body": "What gene test is recommended for clopidogrel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22974536", "http://www.ncbi.nlm.nih.gov/pubmed/22674970", "http://www.ncbi.nlm.nih.gov/pubmed/22464343", "http://www.ncbi.nlm.nih.gov/pubmed/18004210", "http://www.ncbi.nlm.nih.gov/pubmed/18577829", "http://www.ncbi.nlm.nih.gov/pubmed/19706858", "http://www.ncbi.nlm.nih.gov/pubmed/22088980", "http://www.ncbi.nlm.nih.gov/pubmed/22624833", "http://www.ncbi.nlm.nih.gov/pubmed/20435227", "http://www.ncbi.nlm.nih.gov/pubmed/17681590", "http://www.ncbi.nlm.nih.gov/pubmed/22154242", "http://www.ncbi.nlm.nih.gov/pubmed/21803320", "http://www.ncbi.nlm.nih.gov/pubmed/20083681" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0070166", "o": "http://linkedlifedata.com/resource/umls/label/A0173515" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0173515", "o": "clopidogrel" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A12101557", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12785306", "o": "Clopidogrel" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0173516", "o": "MeSH" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10928568", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "The genetic test recommended for clopidogrel is CYP2C19 genotyping." ], "exact_answer": [ "CYP2C19 genotyping" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003955", "http://www.biosemantics.org/jochem#4260620", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005820", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ], "type": "factoid", "id": "5156be04d24251bc05000085", "snippets": [ { "offsetInBeginSection": 607, "offsetInEndSection": 677, "text": "polymorphisms in the CYP2C19 gene affect clopidogrel pharmacokinetics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22674970", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 212, "text": "This study sought to evaluate the influence of single nucleotide polymorphisms (SNPs) on the pharmacodynamic effect of high- or standard-dose clopidogrel after percutaneous coronary intervention (PCI).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22624833", "endSection": "sections.0" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 2056, "text": "CYP2C19, but not PON1 or ABCB1, is a significant determinant of the pharmacodynamic effects of clopidogrel, both early and late after PCI. In patients with high OTR identified by platelet function testing, the CYP2C19 genotype provides limited incremental information regarding the risk of persistently high reactivity with clopidogrel 150-mg maintenance dosing. (Genotype Information and Functional Testing Study [GIFT]; NCT00992420).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22624833", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 324, "text": "Variants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose of the antiplatelet drug clopidogrel. OBJECTIVE: To test whether higher doses (up to 300 mg daily) improve the response to clopidogrel in the setting of loss-of-function CYP2C19 genotypes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088980", "endSection": "sections.0" }, { "offsetInBeginSection": 607, "offsetInEndSection": 920, "text": "polymorphisms in the CYP2C19 gene affect clopidogrel pharmacokinetics. These polymorphisms may be useful to identify clopidogrel nonresponders who may benefit from taking an alternative antiplatelet agent such as prasugrel and ticagrelor. Although both drugs have pharmacogenomic tests available for clinical use,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22674970", "endSection": "sections.0" }, { "offsetInBeginSection": 136, "offsetInEndSection": 497, "text": "The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22464343", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 401, "text": "The antiplatelet effect of clopidogrel has been linked to cytochrome P450 2C19 (CYP2C19) carrier status. The presence of loss of function and gain of function variants were found to have a gene-dose effect on clopidogrel metabolism. However, genotyping is only one aspect of predicting response to clopidogrel and several platelet function tests are available to measure platelet response.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22154242", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The cytochrome P450 (CYP) 2C19*2 loss-of-function allele has been associated with impaired clopidogrel response and worse prognosis in clopidogrel-treated patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803320", "endSection": "sections.0" }, { "offsetInBeginSection": 357, "offsetInEndSection": 637, "text": "The present study was designed to evaluate the benefit of tailored therapy with a higher maintenance dose according to CYP2C19 genotypes in patients identified as nonresponders who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803320", "endSection": "sections.0" }, { "offsetInBeginSection": 893, "offsetInEndSection": 977, "text": "identify genes and mutations with known associations with disease and drug response.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435227", "endSection": "sections.0" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1753, "text": "The patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20435227", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 344, "text": "The cytochrome P450 (CYP) 2C19 isoenzyme plays an important role in clopidogrel metabolization. A recently explored CYP2C19*17 allelic variant has been linked to increased transcriptional activity, resulting in extensive metabolization of CYP2C19 substrates, which may lead to an enhanced platelet response to clopidogrel treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20083681", "endSection": "sections.0" }, { "offsetInBeginSection": 333, "offsetInEndSection": 395, "text": "To identify gene variants that influence clopidogrel response.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19706858", "endSection": "sections.0" }, { "offsetInBeginSection": 608, "offsetInEndSection": 973, "text": "A genome-wide association study was performed followed by genotyping the loss-of-function cytochrome P450 (CYP) 2C19*2 variant (rs4244285). Findings in the PAPI Study were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascular outcomes in an independent sample of 227 patients undergoing percutaneous coronary intervention.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19706858", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 116, "text": "Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18577829", "endSection": "sections.0" }, { "offsetInBeginSection": 439, "offsetInEndSection": 754, "text": "Genotyping revealed 7 carriers of both the C allele of P2Y12 and A allele of CYP2C19 (group 1), 14 carriers of the T allele of P2Y12 and A allele of CYP2C19 (group 2), 17 carriers of the C allele of P2Y12 and G allele of CYP2C19 (group 3) and 67 carriers of the T allele of P2Y12 and G allele of CYP2C19 (controls).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18577829", "endSection": "sections.0" }, { "offsetInBeginSection": 37, "offsetInEndSection": 285, "text": "to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19*2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18004210", "endSection": "sections.0" }, { "offsetInBeginSection": 260, "offsetInEndSection": 337, "text": "to test the influence of the CYP 2C19*2 allele on clopidogrel responsiveness.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17681590", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Genetic polymorphisms significantly influence responses to warfarin and clopidogrel.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22674970", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 286, "text": "A recent clinical trial has demonstrated that patients with acute coronary syndromes (ACS) and the reduced function allele CYP2C19*2 (*2 allele), who are treated with thienopyridines, have an increased risk of adverse cardiac events with clopidogrel, but not with prasugrel.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22974536", "endSection": "sections.0" } ] }, { "body": "What is the role of eteplirsen in DMD patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "http://www.ncbi.nlm.nih.gov/pubmed/24282529" ], "ideal_answer": [ "AVI-4658(eteplirsen) induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection." ], "exact_answer": [ "skipping of dystrophin exon 51" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11723", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009136", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009137", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020388" ], "type": "factoid", "id": "56a24dfffe92d6fd19000002", "snippets": [ { "offsetInBeginSection": 71, "offsetInEndSection": 381, "text": "Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 213, "text": "In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Exon skipping quantification by quantitative reverse-transcription polymerase chain reaction in Duchenne muscular dystrophy patients treated with the antisense oligomer eteplirsen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "endSection": "title" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1002, "text": "morpholino AO to skip exon 51, eteplirsen (AVI-4658).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1239, "text": "We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1477, "text": "We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282529", "endSection": "abstract" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1262, "text": "Here we describe the development of a Taqman quantitative (q)RT-PCR assay to quantify exon skipping and highlight its use to determine the levels of exon skipping in DMD patients treated intramuscularly with a morpholino AO to skip exon 51, eteplirsen (AVI-4658).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 1003, "text": "Here we describe the development of a Taqman quantitative (q)RT-PCR assay to quantify exon skipping and highlight its use to determine the levels of exon skipping in DMD patients treated intramuscularly with a morpholino AO to skip exon 51, eteplirsen (AVI-4658). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 660, "text": "METHODS: DMD boys aged 7 to 13 years, with confirmed deletions correctable by skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 weeks (n\u2009=\u20094/group). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1377, "text": "There was no significant difference in the level of the dystromirs in BMD compared to controls. We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene. The dystromirs were also analysed in muscle biopsies of DMD patients included in a single dose intramuscular eteplirsen clinical trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 702, "text": "We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection. We now show that this dystrophin expression was accompanied by an elevated expression of \u03b1-sarcoglycan, \u03b2-dystroglycan (BDG) and--in relevant cases--neuronal nitric oxide synthase (nNOS) at the sarcolemma, each of which is a component of a different subcomplex of the dystrophin-associated glycoprotein complex (DAPC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "OBJECTIVE: In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51. The present study used a double-blind placebo-controlled protocol to test eteplirsen's ability to induce dystrophin production and improve distance walked on the 6-minute walk test (6MWT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1377, "text": "We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene. The dystromirs were also analysed in muscle biopsies of DMD patients included in a single dose intramuscular eteplirsen clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51. The present study used a double-blind placebo-controlled protocol to test eteplirsen's ability to induce dystrophin production and improve distance walked on the 6-minute walk test (6MWT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 761, "text": "DMD boys aged 7 to 13 years, with confirmed deletions correctable by skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 weeks (n\u2009=\u20094/group). Placebo patients switched to 30 or 50 mg/kg eteplirsen (n=2/group) at week 25; treatment was open label thereafter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 645, "text": "The present study used a double-blind placebo-controlled protocol to test eteplirsen's ability to induce dystrophin production and improve distance walked on the 6-minute walk test (6MWT). DMD boys aged 7 to 13 years, with confirmed deletions correctable by skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 weeks (n\u2009=\u20094/group).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 761, "text": "DMD boys aged 7 to 13 years, with confirmed deletions correctable by skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 weeks (n\u2009=\u20094/group). Placebo patients switched to 30 or 50 mg/kg eteplirsen (n=2/group) at week 25; treatment was open label thereafter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 645, "text": "The present study used a double-blind placebo-controlled protocol to test eteplirsen's ability to induce dystrophin production and improve distance walked on the 6-minute walk test (6MWT).DMD boys aged 7 to 13 years, with confirmed deletions correctable by skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 weeks (n\u2009=\u20094/group).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" } ] }, { "body": "Describe clinical presentation of Parkinsonism with dementia of Guadeloupe syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12217621", "http://www.ncbi.nlm.nih.gov/pubmed/17303592", "http://www.ncbi.nlm.nih.gov/pubmed/21783505", "http://www.ncbi.nlm.nih.gov/pubmed/16092100", "http://www.ncbi.nlm.nih.gov/pubmed/18941145", "http://www.ncbi.nlm.nih.gov/pubmed/18816693", "http://www.ncbi.nlm.nih.gov/pubmed/17702273", "http://www.ncbi.nlm.nih.gov/pubmed/11912113" ], "ideal_answer": [ "Parkinsonism with dementia of Guadeloupe is a unique combination of levodopa-resistant parkinsonism, tremor, myoclonus, hallucinations, REM sleep behavior disorder and fronto-subcortical dementia. Based on the presence or the absence of supranuclear gaze palsy, two subgroups of patients can be distinguished." ], "type": "summary", "id": "56c1f033ef6e39474100004f", "snippets": [ { "offsetInBeginSection": 296, "offsetInEndSection": 583, "text": "The clinical entity was a unique combination of levodopa-resistant parkinsonism, tremor, myoclonus, hallucinations, REM sleep behavior disorder and fronto-subcortical dementia. Based on the presence or the absence of supranuclear gaze palsy, two subgroups of patients were distinguished.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18816693", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 494, "text": "One-half of the patients with this tauopathy have dopa-resistant parkinsonism, tremor, subcortical dementia and abnormal eye movements suggestive of progressive supranuclear palsy (PSP). They also have hallucinations, dysautonomia, which are not characteristic of PSP. Furthermore, the oculomotor abnormalities and the tremor, which is jerky, differ from what is observed in classical PSP patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18941145", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1730, "text": "In conclusion, Gd-PSP patients have cortical myoclonus and cortical oculomotor impairments, but only minor signs of brainstem oculomotor dysfunction, suggesting that cortical dysfunction predominates over brainstem impairments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18941145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "REM sleep behavior disorder in patients with guadeloupean parkinsonism, a tauopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702273", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "STUDY OBJECTIVE: To describe sleep characteristics and rapid eye movement (REM) sleep behavior disorder in patients with Guadeloupean atypical parkinsonism (Gd-PSP), a tauopathy resembling progressive supranuclear palsy that mainly affects the midbrain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702273", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 1033, "text": "RESULTS: REM sleep behavior disorder was found in 78% patients with Gd-PSP (43% of patients reported having this disorder several years before the onset of parkinsonism), 44% of patients with idiopathic Parkinson disease, 33% of patients with progressive supranuclear palsy, and no controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702273", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1599, "text": "CONCLUSION: Although Gd-PSP is a tauopathy, most patients experience REM sleep behavior disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702273", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 299, "text": "Only one-third of the patients that develop parkinsonian symptoms were reported to present the classical features of idiopathic Parkinson disease and one-third a syndrome resembling progressive supranuclear palsy (PSP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17303592", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1679, "text": "Patients with a PSP-like syndrome developed levodopa-resistant parkinsonism, associated with early postural instability and supranuclear oculomotor dysfunction. They differed, however, from classical PSP patients by the frequency of tremor (>50%), dysautonomia (50%) and the occurrence of hallucinations (59%). PDC patients had levodopa-resistant parkinsonism associated with frontosubcortical dementia, 52% of these patients had hallucinations, but, importantly, none had oculomotor dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17303592", "endSection": "abstract" }, { "offsetInBeginSection": 1754, "offsetInEndSection": 2450, "text": "Cerebral atrophy was seen in the majority of the PSP-like and PDC patients, with enlargement of the third ventricle and marked T2-hypointensity in the basal ganglia, particularly the substantia nigra. Consumption of soursop was significantly greater in both PSP-like and PDC patients than in controls and Parkinson's disease patients. In conclusion, atypical Guadeloupean parkinsonism comprises two forms of parkinsonism and dementia that differ clinically by the presence of oculomotor signs, but have similar cognitive profiles and neuroimaging features, suggesting that they may constitute a single disease entity, and both were similarly exposed to annonaceous neurotoxins, notably annonacin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17303592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Guadeloupean parkinsonism: a cluster of progressive supranuclear palsy-like tauopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11912113", "endSection": "title" }, { "offsetInBeginSection": 128, "offsetInEndSection": 380, "text": "Postural instability with early falls, prominent frontal lobe dysfunction and pseudo-bulbar palsy were common and three-quarters of the patients were L-dopa unresponsive. One-third of all patients seen had probable progressive supranuclear palsy (PSP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11912113", "endSection": "abstract" }, { "offsetInBeginSection": 1947, "offsetInEndSection": 2037, "text": "Guadeloupean parkinsonism may prove to be a tauopathy identical or closely related to PSP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11912113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Progressive supranuclear palsy and its relation to pacific foci of the parkinsonism-dementia complex and Guadeloupean parkinsonism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12217621", "endSection": "title" }, { "offsetInBeginSection": 147, "offsetInEndSection": 299, "text": " Now on Guadeloupe in the Carribbean French West Indies, Caparros-Lefebvre is identifying many patients with similar clinical and histological features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12217621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": ": On Guadeloupe, atypical parkinsonism is abnormally frequent, and represents 75% of progressive parkinsonism while Parkinson's disease (PD) accounts for only 25%, which is an inversed percentage in comparison with Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21783505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "On the French West Indian island of Guadeloupe, atypical parkinsonian patients represent two-thirds of all cases of parkinsonism, which is exceptionally frequent compared to epidemiological data from European countries where atypical parkinsonism accounts for only approximately 5% of all cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18816693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Atypical unclassifiable parkinsonism on Guadeloupe: an environmental toxic hypothesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16092100", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "In Guadeloupe, there is an abnormally high frequency of atypical parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17303592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17303592", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Atypical parkinsonism is extremely frequent in Guadeloupe and may have an environmental cause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18941145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Atypical parkinsonism in the Caribbean island of Guadeloupe: etiological role of the mitochondrial complex I inhibitor annonacin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18816693", "endSection": "title" }, { "offsetInBeginSection": 2496, "offsetInEndSection": 2716, "text": "The development of atypical parkinsonism in Guadeloupe and probably elsewhere, could result from synergistic toxicity, but acetogenins are probably the most potent neurotoxin, acting as mitochondrial complex I inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16092100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Atypical parkinsonism on Guadeloupe, comparison with the parkinsonism-dementia complex of Guam, and environmental toxic hypotheses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21783505", "endSection": "title" }, { "offsetInBeginSection": 757, "offsetInEndSection": 920, "text": "Two hundred and twenty consecutive patients with Parkinson's syndrome seen by the neurology service at Pointe \u00e0 Pitre, Guadeloupe University Hospital were studied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11912113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "We characterize the clinical features of Parkinson's syndrome on Guadeloupe and describe possible environmental causes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16092100", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 591, "text": "The subjects were 265 patients with Parkinson's syndrome living on Guadeloupe,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16092100", "endSection": "abstract" } ] }, { "body": "Does the concentration of protein HIF-1\u03b1 increase after the administration of the cytoprotective prodrug\"amifostine\" (ethyol) ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "http://www.ncbi.nlm.nih.gov/pubmed/24147016", "http://www.ncbi.nlm.nih.gov/pubmed/20334641", "http://www.ncbi.nlm.nih.gov/pubmed/19478935", "http://www.ncbi.nlm.nih.gov/pubmed/21875443", "http://www.ncbi.nlm.nih.gov/pubmed/21452059", "http://www.ncbi.nlm.nih.gov/pubmed/14574457" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/5132", "o": "Intervention #5132 (Drug:Ethyol (Amifostine))" } ], "ideal_answer": [ "The key-protein that when associated with HREs leads to the activation of all of these genes, is identified as\u201cHypoxia Inducible Factor-1\u201d (HIF1). It is a heterodimer composed of two subunits (IIF1a 120kDa and HIF-1b 91-94kDa), both of which belong to the group of \"basic helix-loop-helix\" (bHLH)-Pas proteins. The heterodimer HIF1 and IIF2 increase in the cytoplasm of cells exposed to hypoxia." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/HIF1A_BOSMU", "http://www.biosemantics.org/jochem#4217067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011355", "http://www.biosemantics.org/jochem#4277891", "http://www.uniprot.org/uniprot/HIF1A_EOSBA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004999", "http://www.uniprot.org/uniprot/HIF1A_ONCMY" ], "type": "yesno", "id": "533eb89fc45e133714000012", "snippets": [ { "offsetInBeginSection": 933, "offsetInEndSection": 1126, "text": "We demonstrated that the treatment of several human cancer cell lines with therapeutical doses of WR-1065 led to a strong induction of different VEGF-A mRNA isoforms independently of HIF-1alpha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334641", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 364, "text": "e investigated the involvement of hypoxia-regulated proteins (Hypoxia inducible factors HIF1alpha, HIF2alpha and carbonic anhydrase CA9) in HNC resistance to accelerated and hypofractionated radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1867, "text": "In accord with previously reported studies, high levels of the hypoxia regulated proteins HIF1alpha and CA9 in HNC predict resistance to platinum based radio-chemotherapy. Whether HIF2alpha expressing tumors are more sensitive to larger radiotherapy fractions, compared to standard radiotherapy fractionation, is an issue that deserves further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1413, "text": "HIF1alpha and HIF2alpha were expressed in the nuclei and cytoplasm of cancer cells, while CA9 had a membrane reactivity. A high expression of HIF1alpha, HIF2alpha and CA9 was noted in 21/39 (53.8%), 20/39 (51.3%) and 23/39 (58.9%) cases, respectively. Complete response was obtained in 85.2% of patients and HIF1alpha was marginally related with persistent disease after RT (p = 0.05). HIF1alpha was significantly associated with poor local relapse free survival (LRFS) (p = 0.006) and overall survival (p = 0.008), whilst HIF2alpha was no", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852557", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 875, "text": " The glucose and oxygen levels in the peripheral blood of patients receiving 1000 mg amifostine were determined at various time-points in order to investigate the metabolic changes induced by amifostine. MDA468 breast tumor cell lines were incubated with a high amifostine concentration (10 m M) to overcome the natural resistance of cancer cells to influx of the non-hydrolyzed WR-2721, and the HIF1 alpha protein levels were determined by Western blot analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14574457", "endSection": "abstract" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1854, "text": "Since it is doubtful whether dephosphorylation of amifostine to the active metabolite WR-1065 occurs within tumoral tissues (an acidic environment that lacks vascular alkaline phosphatase activity), intracellular hypoxia and upregulation of HIF1 alpha represents an additional, normal tissue-specific, amifostine cytoprotective pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14574457", "endSection": "abstract" }, { "offsetInBeginSection": 1319, "offsetInEndSection": 1394, "text": ". Incubation of cell lines with amifostine resulted in HIF1 alpha induction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14574457", "endSection": "abstract" } ] }, { "body": "Which diseases can Oncotype DX be used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19946260", "http://www.ncbi.nlm.nih.gov/pubmed/19101988", "http://www.ncbi.nlm.nih.gov/pubmed/21221771", "http://www.ncbi.nlm.nih.gov/pubmed/21934103", "http://www.ncbi.nlm.nih.gov/pubmed/23074401", "http://www.ncbi.nlm.nih.gov/pubmed/21176237", "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "http://www.ncbi.nlm.nih.gov/pubmed/22811953", "http://www.ncbi.nlm.nih.gov/pubmed/22590486", "http://www.ncbi.nlm.nih.gov/pubmed/23371261", "http://www.ncbi.nlm.nih.gov/pubmed/18347556", "http://www.ncbi.nlm.nih.gov/pubmed/19125125", "http://www.ncbi.nlm.nih.gov/pubmed/20200857", "http://www.ncbi.nlm.nih.gov/pubmed/18072276", "http://www.ncbi.nlm.nih.gov/pubmed/21278441", "http://www.ncbi.nlm.nih.gov/pubmed/22361999", "http://www.ncbi.nlm.nih.gov/pubmed/18942607", "http://www.ncbi.nlm.nih.gov/pubmed/21370017", "http://www.ncbi.nlm.nih.gov/pubmed/19536946", "http://www.ncbi.nlm.nih.gov/pubmed/20877447", "http://www.ncbi.nlm.nih.gov/pubmed/20564629" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10812803", "o": "Oncotype DX" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7568412", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0049608" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0015570", "o": "Diseases" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A18169310", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0015569", "o": "Diseases" } ], "ideal_answer": [ "Oncotype can be used for predicting breast cancer and colon cancer recurrence." ], "exact_answer": [ [ "breast cancer" ], [ "colon cancer" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001941", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003108", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003109" ], "type": "list", "id": "514a11add24251bc05000054", "snippets": [ { "offsetInBeginSection": 243, "offsetInEndSection": 276, "text": "Prognostic and predictive markers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371261", "endSection": "sections.0" }, { "offsetInBeginSection": 366, "offsetInEndSection": 440, "text": "Oncotype DX\u00ae currently allow avoidance of an over therapy or under therapy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371261", "endSection": "sections.0" }, { "offsetInBeginSection": 432, "offsetInEndSection": 489, "text": "a high score on the Oncotype DX gene expression profile r", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22590486", "endSection": "sections.0" }, { "offsetInBeginSection": 191, "offsetInEndSection": 267, "text": "poor-prognosis ER-positive breast cancers in need of more aggressive therapy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22590486", "endSection": "sections.0" }, { "offsetInBeginSection": 316, "offsetInEndSection": 331, "text": "luminal B class", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22590486", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The 21-gene recurrence score (Oncotype DX: RS) appears to augment clinico-pathologic prognostication and is predictive of adjuvant chemotherapy benefit in node-negative (N-) and node-positive (N+), endocrine-sensitive breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22361999", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 263, "text": "Half of all breast cancers are early stage, lymph node negative, and hormone receptor positive. A 21-gene (Oncotype DX\u00ae; Genomic Health, Inc., Redwood City, CA) recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21934103", "endSection": "sections.0" }, { "offsetInBeginSection": 270, "offsetInEndSection": 503, "text": "We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "endSection": "sections.0" }, { "offsetInBeginSection": 1350, "offsetInEndSection": 1694, "text": "Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "endSection": "sections.0" }, { "offsetInBeginSection": 620, "offsetInEndSection": 879, "text": "Molecular tests such as the Oncotype DX(\u00ae) breast cancer test are proving to be more effective tools for individualized patient stratification and treatment planning than traditional methods such as patient demographic variables and histopathology indicators.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21370017", "endSection": "sections.0" }, { "offsetInBeginSection": 1546, "offsetInEndSection": 1763, "text": "Node-negative breast cancer does not automatically suggest a good prognosis, or the preclusion of chemotherapy benefits, and additional biomarkers are needed to help identify patients who do benefit from chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21278441", "endSection": "sections.0" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1325, "text": "The oncotype DX\u00ae genomic assay has also been used to help prognosis estimation and treatment decisions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21278441", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The Oncotype DX Recurrence Score (RS) is a validated genomic predictor of outcome and response to adjuvant chemotherapy in ER-positive breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21221771", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 148, "text": "The 21-gene signature has been intensively studied and incorporated into major guidelines for treatment decision in early breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20564629", "endSection": "sections.0" }, { "offsetInBeginSection": 1467, "offsetInEndSection": 1611, "text": "Among early-stage breast cancer patients who received Oncotype DX, we found low knowledge about many aspects of genomic recurrence risk testing.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20200857", "endSection": "sections.0" }, { "offsetInBeginSection": 699, "offsetInEndSection": 1137, "text": "the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets, such as luminal A and B, basal, normal-like, and ERBB2+, and prognostic signatures including MammaPrint and Oncotype DX, predicted genomic instability in our samples. This remarkable congruence suggests a biological interdependence of poor-prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19101988", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "The Oncotype DX assay is one of the molecular tests that provide predictive and prognostic information to breast cancer patients with estrogen receptor (ER)-positive and node-negative disease. This study evaluates the association of Forkhead-box protein A1 (FOXA1) and GATA-binding protein 3 (GATA3) expressions with Oncotype DX recurrences scores in 77 cases of patients with ER-positive node-negative breast carcinomas diagnosed at Indiana University.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19946260", "endSection": "sections.0" }, { "offsetInBeginSection": 30, "offsetInEndSection": 485, "text": "the use of the Oncotype DX assay in estrogen receptor-positive node-negative breast cancer patients were incorporated into guidelines from both the American Society of Clinical Oncology and the National Comprehensive Cancer Network. The Oncotype DX assay is a diagnostic test which measures changes in a set of 21 genes in order to predict the likelihood of disease recurrence and also to predict which patients are most likely to respond to chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19536946", "endSection": "sections.0" }, { "offsetInBeginSection": 1920, "offsetInEndSection": 2089, "text": "The EWG found adequate evidence regarding the association of the Oncotype DX Recurrence Score with disease recurrence and adequate evidence for response to chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125125", "endSection": "sections.0" }, { "offsetInBeginSection": 53, "offsetInEndSection": 239, "text": "EWG) found insufficient evidence to make a recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women with breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19125125", "endSection": "sections.0" }, { "offsetInBeginSection": 230, "offsetInEndSection": 424, "text": "confirmed the clinical validity of the Oncotype DX breast cancer assay, not only as a way to predict recurrence but also as a tool for determining therapeutic benefit from adjuvant chemotherapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347556", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Over several decades, investigators working through National Cancer Institute-sponsored Cooperative Groups have contributed to major advances in the endocrine treatment of breast cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18072276", "endSection": "sections.0" }, { "offsetInBeginSection": 586, "offsetInEndSection": 775, "text": "Cooperative Group studies have contributed to the development of a molecular profiling test, Oncotype Dx, which identifies women who have an excellent prognosis with hormonal therapy alone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18072276", "endSection": "sections.0" }, { "offsetInBeginSection": 359, "offsetInEndSection": 485, "text": "In this report we compare the prognostic and predictive utility of these two tools in node-negative, ER-positive breast cancer", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21221771", "endSection": "sections.0" }, { "offsetInBeginSection": 2732, "offsetInEndSection": 3135, "text": "The Oncotype-DX Breast Cancer Assay (Genomic Health, Redwood City, CA) quantifies gene expression for 21 genes in breast cancer tissue by performing reverse transcription polymerase chain reaction (RT-PCR) on formalin-fixed paraffin-embedded (FFPE) tumour blocks that are obtained during initial surgery (lumpectomy, mastectomy, or core biopsy) of women with early breast cancer that is newly diagnosed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074401", "endSection": "sections.0" }, { "offsetInBeginSection": 297, "offsetInEndSection": 478, "text": "78 women, treated for early-stage, estrogen receptor-positive breast cancer with 0-3 positive lymph nodes, whose medical records indicated they received Oncotype DX testing earlier.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20200857", "endSection": "sections.0" }, { "offsetInBeginSection": 226, "offsetInEndSection": 427, "text": "A retrospective chart review of 58 T1/T2, node-negative, estrogen-receptor positive breast cancer patients that underwent Oncotype DX gene assay testing between January and December 2006 was performed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18942607", "endSection": "sections.0" } ] }, { "body": "Which are the DNA (cytosine-5-)-methyltransferases inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9925782", "http://www.ncbi.nlm.nih.gov/pubmed/7536414", "http://www.ncbi.nlm.nih.gov/pubmed/20808780", "http://www.ncbi.nlm.nih.gov/pubmed/21981419", "http://www.ncbi.nlm.nih.gov/pubmed/12368098", "http://www.ncbi.nlm.nih.gov/pubmed/21796622", "http://www.ncbi.nlm.nih.gov/pubmed/11838638", "http://www.ncbi.nlm.nih.gov/pubmed/23007409", "http://www.ncbi.nlm.nih.gov/pubmed/9207024", "http://www.ncbi.nlm.nih.gov/pubmed/22382314", "http://www.ncbi.nlm.nih.gov/pubmed/21842375", "http://www.ncbi.nlm.nih.gov/pubmed/22280363", "http://www.ncbi.nlm.nih.gov/pubmed/22203734", "http://www.ncbi.nlm.nih.gov/pubmed/19322801", "http://www.ncbi.nlm.nih.gov/pubmed/20139415", "http://www.ncbi.nlm.nih.gov/pubmed/12206775", "http://www.ncbi.nlm.nih.gov/pubmed/23085465", "http://www.ncbi.nlm.nih.gov/pubmed/22170584", "http://www.ncbi.nlm.nih.gov/pubmed/9628353", "http://www.ncbi.nlm.nih.gov/pubmed/23444399", "http://www.ncbi.nlm.nih.gov/pubmed/22398368", "http://www.ncbi.nlm.nih.gov/pubmed/19467223", "http://www.ncbi.nlm.nih.gov/pubmed/23125037", "http://www.ncbi.nlm.nih.gov/pubmed/21805123", "http://www.ncbi.nlm.nih.gov/pubmed/22320963", "http://www.ncbi.nlm.nih.gov/pubmed/22259221", "http://www.ncbi.nlm.nih.gov/pubmed/9153756", "http://www.ncbi.nlm.nih.gov/pubmed/21791605" ], "ideal_answer": [ "DNA (Cytosine-5-)-methyltransferases are a family of enzymes that methylate DNA at the C5 position of cytosine residues. Given that methylation of tumour suppressor gene promoters leads to carcinogenesis, inhibition of DNA (Cytosine-5-)-methyltransferases is a promising strategy for the treatment of cancer. There are several inhibitors of DNA (Cytosine-5-)-methyltransferases that uses different modes of action: 5-azacytidine (5-aza-CR, Vidaza\u00ae), 5-azadeoxycytidine (5-aza-CdR, decitabine, Dacogen\u00ae), 5-azacytosine (ZCyt), 5-fluorodeoxycytidine (FdC), 5,6-dihydro-5-azacytosine (DZCyt), 4'-thio-2'-deoxycytidine, hydralazine, 2-(1H)-pyrimidinone riboside (zebularine), 2-(1H)-pyrimidinone (zebularine aglycon), procaine, procainamide, psammaplin A, and RSC133, a new synthetic derivative of indoleacrylic acid/indolepropionic acid." ], "exact_answer": [ [ "5-azacytidine", "5-aza-CR", "Vidaza\u00ae" ], [ "5-azadeoxycytidine", "5-aza-CdR", "Dacogen\u00ae", "5-aza-2'-deoxycytidine", "Decitabine" ], [ "5-azacytosine", "ZCyt" ], [ "5-fluorodeoxycytidine", "FdC" ], [ "5,6-dihydro-5-azacytosine", "DZCyt" ], [ "4'-thio-2'-deoxycytidine" ], [ "hydralazine" ], [ "2-(1H)-pyrimidinone riboside", "zebularine" ], [ "2-(1H)-pyrimidinone", "zebularine aglycon" ], [ "procaine" ], [ "procainamide" ], [ "RSC133" ], [ "Psammaplin A" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248", "http://www.uniprot.org/uniprot/DCM_ECOLI", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ], "type": "list", "id": "5165932e298dcd4e51000059", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "5-Aza-2'-deoxycytidine (5-Aza-CdR), a nucleoside analog that can inhibit DNA cytosine methylation, possesses potent antitumorigenic activities for myeloid disorders. Although 5-Aza-CdR is known to be incorporated into DNA and inhibit DNA (cytosine-5)-methyltransferases, the precise mechanisms underlying the drug's antineoplastic activity remain unclear.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22398368", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The mechanism of inhibition of DNA (cytosine-5-)-methyltransferases by 5-azacytosine is likely to involve methyl transfer to the inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7536414", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "The mechanism of inhibition of DNA (cytosine-5-)-methyltransferases by the mechanism-based inhibitor 5-azacytosine has remained unclear, mainly because of the unavailability of a substrate in which the inhibitor, but not normal cytosine, is present at the target site.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7536414", "endSection": "sections.0" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1084, "text": "These results suggest that, when the enzyme binds to 5-azacytosine in the presence of the cofactor, a methyl group is transferred to the N-5 position of the base, resulting in the inactivation of the enzyme.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7536414", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Rapid synthesis of new DNMT inhibitors derivatives of procainamide.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22170584", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 475, "text": "Six compounds resulted in potent inhibitors of the murine catalytic Dnmt3A/3L complex and of human DNMT1, at least 50 times greater than that of the parent compounds. The inhibitors showed selectivity for C5 DNA methyltransferases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22170584", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "DNA (Cytosine-C5) methyltransferase inhibition by oligodeoxyribonucleotides containing 2-(1H)-pyrimidinone (zebularine aglycon) at the enzymatic target site.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19467223", "endSection": "title" }, { "offsetInBeginSection": 110, "offsetInEndSection": 346, "text": "A number of DNA methyltransferase inhibitors are known to reactivate silenced genes; including 5-azacytidine and 2-(1H)-pyrimidinone riboside (zebularine). Zebularine is a more stable, less cytotoxic inhibitor compared to 5-azacytidine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19467223", "endSection": "sections.0" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1549, "text": "ODNs containing 2-(1H)-pyrimidinone at the enzymatic target site are competitive inhibitors of both prokaryotic and mammalian DNA C5 methyltransferases. We determined that the ternary complexes between the enzymes, 2-(1H)-pyrimidinone inhibitor, and the cofactor S-adenosyl methionine are maintained through the formation of a reversible covalent interaction. The differing stability and reversibility of the covalent bonds may partially account for the observed differences in cytotoxicity between zebularine and 5-azacytidine inhibitors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19467223", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "DNA methyltransferases (DNMTs) are a family of enzymes that methylate DNA at the C5 position of cytosine residues, and their inhibition is a promising strategy for the treatment of various developmental and proliferative diseases, particularly cancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19322801", "endSection": "sections.0" }, { "offsetInBeginSection": 577, "offsetInEndSection": 813, "text": "The inhibitory activity of hydralazine toward DNMT may be rationalized at the molecular level by similar interactions within the binding pocket (e.g., by a similar pharmacophore) as established by substrate-like deoxycytidine analogues.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19322801", "endSection": "sections.0" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1307, "text": "Despite the different scaffolds of other non-nucleoside DNMT inhibitors such as procaine and procainamide, the current modeling work reveals that these drugs exhibit similar interactions within the DNMT1 binding site. These findings are valuable in guiding the rational design and virtual screening of novel DNMT inhibitors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19322801", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Inhibition of HhaI DNA (Cytosine-C5) methyltransferase by oligodeoxyribonucleotides containing 5-aza-2'-deoxycytidine: examination of the intertwined roles of co-factor, target, transition state structure and enzyme conformation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12368098", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The presence of 5-azacytosine (ZCyt) residues in DNA leads to potent inhibition of DNA (cytosine-C5) methyltranferases (C5-MTases) in vivo and in vitro.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12368098", "endSection": "sections.0" }, { "offsetInBeginSection": 342, "offsetInEndSection": 444, "text": "Thus, it is important to understand the critical mechanistic determinants of ZCyt's inhibitory action.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12368098", "endSection": "sections.0" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1470, "text": "Since methyl transfer can occur only in the presence of AdoMet, these results suggest (1) that the inhibitory capacity of ZCyt in DNA is based on its ability to induce a stable, tightly closed conformation of M.HhaI that prevents DNA and co-factor release and (2) that methylation of ZCyt in DNA is not required for inhibition of M.HhaI.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12368098", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12206775", "endSection": "title" }, { "offsetInBeginSection": 192, "offsetInEndSection": 474, "text": "The inhibition of cytosine-[C5]-specific DNA methyltransferases (C5 MTases) by oligodeoxynucleotides containing 5-azadeoxycytidine (AzadC) and 5-fluorodeoxycytidine (FdC) provides a well-documented example of mechanism-based inhibition of enzymes central to nucleic acid metabolism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12206775", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Synthesis of oligonucleotide inhibitors of DNA (Cytosine-C5) methyltransferase containing 5-azacytosine residues at specific sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11838638", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The incorporation of 5-azacytosine residues into DNA causes potent inhibition of DNA (Cytosine-C5) methyltransferases. T", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11838638", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Mechanism of inhibition of DNA (cytosine C5)-methyltransferases by oligodeoxyribonucleotides containing 5,6-dihydro-5-azacytosine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925782", "endSection": "title" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1059, "text": "Substitution of DZCyt for target cytosines in C-G dinucleotides of single-stranded or double-stranded oligodeoxyribonucleotide substrates led to complete inhibition of methylation by murine DNA C5-MTase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925782", "endSection": "sections.0" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1458, "text": "Oligodeoxyribonucleotides containing DZCyt formed a tight but reversible complex with M.HhaI, and were consistently more potent as inhibitors of DNA methylation than oligodeoxyribonucleotides identical in sequence containing 5-fluorocytosine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925782", "endSection": "sections.0" }, { "offsetInBeginSection": 1927, "offsetInEndSection": 2154, "text": "These results indicate that DZCyt can occupy the active site of M.HhaI as a transition state mimic and, because of the high degree of affinity of its interaction with the enzyme, it can act as a potent inhibitor of methylation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925782", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Analysis of DNA methylation processes related to the inhibition of DNA synthesis by 5-azacytidine in Streptomyces antibioticus ETH 7451.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9628353", "endSection": "title" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1215, "text": "Our results suggest that some of the 5-azacytidine effects on DNA and RNA synthesis might indeed be related to the complex formation and inhibition of a cytosine-specific DNA methyltransferase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9628353", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "DNA containing 4'-thio-2'-deoxycytidine inhibits methylation by HhaI methyltransferase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9207024", "endSection": "title" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1260, "text": "The inhibitory effect of the 4'sulfur atom on enzymatic activity may be traced to perturbation of a step in the methylation reaction after DNA binding but prior to methyl transfer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9207024", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Treatment of Schizosaccharomyces pombe with the C5 DNA methyltransferase (C5Mtase) inhibitor 5-azacytidine (5-azaC) has previously been shown to induce G2 checkpoint-dependent cell cycle arrest.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9153756", "endSection": "sections.0" }, { "offsetInBeginSection": 185, "offsetInEndSection": 379, "text": "Inhibitors of DNA methyltransferase (Dnmt) enzymes have been advocated as a means to promote and stabilize Foxp3 expression in Tregs undergoing expansion in vitro before their injection in vivo.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444399", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Booster of pluripotency: RSC133, a new synthetic derivative of indoleacrylic acid/indolepropionic acid, exhibits dual activity by inhibiting histone deacetylase and DNA methyltransferase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23125037", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "DNA methyltransferase inhibitors (DNMTIs), including decitabine (DAC) and azacitidine (AZA), have recently been highlighted for the treatment of high-risk myelodysplastic syndrome (MDS); however, their action mechanisms have not been clearly defined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085465", "endSection": "sections.0" }, { "offsetInBeginSection": 297, "offsetInEndSection": 463, "text": "Structurally, however, gemcitabine has similarities to 5-aza-2-deoxycytidine (decitabine/Dacogen\u00ae), a DNA methyltransferase inhibitor (DNMTi).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23007409", "endSection": "sections.0" }, { "offsetInBeginSection": 166, "offsetInEndSection": 355, "text": "Although 5-Aza-CdR is known to be incorporated into DNA and inhibit DNA (cytosine-5)-methyltransferases, the precise mechanisms underlying the drug's antineoplastic activity remain unclear.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22398368", "endSection": "sections.0" }, { "offsetInBeginSection": 275, "offsetInEndSection": 488, "text": "Human colon cancer cell lines (HCT116, HT29, SW48, SW480) were treated with 5-aza-2'-deoxycytidine (DAC), as a DNA methyltransferase inhibitor, followed by trichostatin A (TSA), as a histone deacetylase inhibitor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22382314", "endSection": "sections.0" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1085, "text": "With increasing 5-Aza-CdR concentrations, the expression of DNA methyltransferases, DNMT3A and DNMT3B, significantly decreased in a dose-dependent manner.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22320963", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22280363", "endSection": "sections.0" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1660, "text": "Defining the parameters of zebularine-mediated tumor inhibition may advance the future development of DNA methyltransferase inhibitors as an effective cancer treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22203734", "endSection": "sections.0" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1272, "text": "The DNA methyltransferase inhibitor (5-aza-2-deoxycytidine) and the histone deacetylase inhibitor [trichostatin A (TSA)] both significantly up-regulated miR-146a transcriptional activation by altering the DNA-binding activity of NF-\u03baB in macrophages isolated from aged mice, which suggests that DNA methylation and histone acetylation are involved in the suppression of age-dependent miR-146a expression.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21981419", "endSection": "sections.0" }, { "offsetInBeginSection": 102, "offsetInEndSection": 260, "text": "Diverse DNA methyltransferase inhibitors are being studied as potential anticancer drugs, and there is interest in developing novel and more effective DNMTIs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21842375", "endSection": "sections.0" }, { "offsetInBeginSection": 120, "offsetInEndSection": 236, "text": "Currently, there are only a few DNMT1 inhibitors with potential application as therapeutic agents or research tools.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21805123", "endSection": "sections.0" }, { "offsetInBeginSection": 376, "offsetInEndSection": 546, "text": "The effects of the deoxycytidine analogue decitabine (5-aza-2'-deoxycytidine), which depletes DNA methyl transferase 1 (DNMT1), on melanoma differentiation were examined.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21796622", "endSection": "sections.0" }, { "offsetInBeginSection": 234, "offsetInEndSection": 386, "text": "Cooperative action of HDACi and DNA methylation inhibitors (DNMTi) has been reported, making combined treatment an attractive choice for cancer therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21791605", "endSection": "sections.0" } ] }, { "body": "Describe armoured brain syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24403965", "http://www.ncbi.nlm.nih.gov/pubmed/1580196", "http://www.ncbi.nlm.nih.gov/pubmed/19902386", "http://www.ncbi.nlm.nih.gov/pubmed/21319032", "http://www.ncbi.nlm.nih.gov/pubmed/23421586" ], "ideal_answer": [ "Armoured brain syndrome is defined by calcified chronic subdural haematoma." ], "type": "summary", "id": "54cf42bdf693c3b16b000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Armoured brain is a rare condition where dense calcification occurs over the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24403965", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 83, "text": "Armoured brain due to chronic subdural collections masking underlying hydrocephalus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23421586", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Calcified chronic subdural collection (armoured brain) is a known long-standing complication of shunt overdrainage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23421586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "The optimal surgical procedure for patients with calcified and organized chronic subdural haematoma (CSDH), or \"armoured brain\", has not been established because it is difficult to obtain good re-expansion of the brain after surgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21319032", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 647, "text": "RESULTS: A patient with a bilateral symptomatic calcified chronic subdural hematoma, or so-called \"armoured brain\", was admitted to our intensive care unit with clinical signs of increased intracranial pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19902386", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 110, "text": "High-field magnetic resonance image of a huge calcified chronic subdural haematoma, so-called \"armoured brain\".", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1580196", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Calcification of chronic subdural haematoma is called \"armoured brain\" when it covers most of the cortical surface. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1580196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Calcified chronic subdural collection (armoured brain) is a known long-standing complication of shunt overdrainage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23421586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Armoured brain is a rare condition where dense calcification occurs over the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24403965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The optimal surgical procedure for patients with calcified and organized chronic subdural haematoma (CSDH), or \"armoured brain\", has not been established because it is difficult to obtain good re-expansion of the brain after surgery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21319032", "endSection": "abstract" } ] }, { "body": "Which are the main histone modifications associated with enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20621055", "http://www.ncbi.nlm.nih.gov/pubmed/22270183", "http://www.ncbi.nlm.nih.gov/pubmed/19021773" ], "ideal_answer": [ "Histone 3 lysine 4 mono- (H3K4me1) and di-methylation (H3K4me2) are the main post-transcriptional histone modifications related to enhancer activity.", "Using H3K4me2 as a mark for active enhancers (PMID: 22270183) Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances (PMID: 19021773) The enhancer region itself was marked by mono-methylation at K4 and K9, distinguishing it from the methyl marks in the gene coding region (PMID: 19021773) H3K4 methylation to monovalent and bivalent domains (PMID: 20621055)", "H3K4 methylation to monovalent and bivalent domains. The enhancer region itself was marked by mono-methylation at K4 and K9, distinguishing it from the methyl marks in the gene coding region. Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances. Using H3K4me2 as a mark for active enhancers. " ], "exact_answer": [ [ "Histone 3 lysine 4 mono-methylation (H3K4me1)" ], [ "Histone 3 lysine 4 di-methylation (H3K4me2)" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056545" ], "type": "list", "id": "5131bef65274a5fb07000008", "snippets": [ { "offsetInBeginSection": 202, "offsetInEndSection": 246, "text": "Using H3K4me2 as a mark for active enhancers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270183", "endSection": "sections.0" }, { "offsetInBeginSection": 101, "offsetInEndSection": 257, "text": "Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19021773", "endSection": "sections.0" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1018, "text": "The enhancer region itself was marked by mono-methylation at K4 and K9, distinguishing it from the methyl marks in the gene coding region", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19021773", "endSection": "sections.0" }, { "offsetInBeginSection": 300, "offsetInEndSection": 351, "text": "H3K4 methylation to monovalent and bivalent domains", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20621055", "endSection": "sections.0" } ] }, { "body": "What is the role of Thyrotropin Releasing Hormone in the treatment of comatose patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3018425", "http://www.ncbi.nlm.nih.gov/pubmed/8221703", "http://www.ncbi.nlm.nih.gov/pubmed/9773038", "http://www.ncbi.nlm.nih.gov/pubmed/2112565", "http://www.ncbi.nlm.nih.gov/pubmed/2127684", "http://www.ncbi.nlm.nih.gov/pubmed/8690305", "http://www.ncbi.nlm.nih.gov/pubmed/8437381", "http://www.ncbi.nlm.nih.gov/pubmed/1317658", "http://www.ncbi.nlm.nih.gov/pubmed/1394244" ], "ideal_answer": [ "Thyrotropin Releasing Hormone and its analogs are used for treatment of comatose patients. In animal models, Thyrotropin Releasing Hormone and its analogs have been shown to improve the disturbance of consciousness caused by head concussion and pentobarbital. This analeptic action is attributable to stimulation of cholinergic neurons in the septo-hippocampal area and to the presence of terminals containing TRH in the lateral septum and TRH receptors concentrated especially in the medial septum and diagonal band of Broca. It has also been suggested that TRH localized in the pineal gland has a part in activating the neuronal mechanisms of arousal. Associated with the arousal effect and especially evident in variously originated shock conditions are the activating effects of TRH on vegetative functions (body temperature, circulation, the gastrointestinal tract). These stimulatory activities on the CNS were the rationale for therapeutic use of TRH in the initial treatment of coma due to brain trauma. Thyrotropin Releasing Hormone has been shown to induce recovery in comatose patients with extrapontine and pontine myelinosis syndromes." ], "concepts": [ "http://www.uniprot.org/uniprot/TRH_NOTVI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013973", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.uniprot.org/uniprot/TRH_BOMOR", "http://www.biosemantics.org/jochem#4272308", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003128", "http://www.uniprot.org/uniprot/TRH_PIG", "http://www.uniprot.org/uniprot/TRH_SHEEP" ], "type": "summary", "id": "530f7d7fe3eabad021000002", "snippets": [ { "offsetInBeginSection": 332, "offsetInEndSection": 835, "text": "Despite the correction of these metabolic disorders, the patient became comatose, and MRI, on T2 weighted image, showed hyperintense signals in the basal ganglia consistent with extra-pontine myelinolysis. The patient's state remained unchanged for six weeks. Since S. Konno and H. Wakui published cases of myelinolysis who dramatically improved after TRH treatment, the patient was given 0.6 mg i.v daily of TRH for six weeks. Improvement began within a few days, and continued until complete recovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9773038", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 927, "text": "His CNS symptoms improved dramatically after administration of thyrotropin-releasing hormone tartrate (TRH-T).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8437381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "[Montirelin hydrate (NS-3), a TRH analog, improved the disturbance of consciousness caused by head concussion and pentobarbital in mice].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8690305", "endSection": "title" }, { "offsetInBeginSection": 291, "offsetInEndSection": 714, "text": "NS-3 shortened the latent periods to the recovery of the righting reflex (0.03-0.1 mg/kg, i.v.) and spontaneous motor activity (0.1 mg/kg, i.v.) following the head concussion. In the case of TRH, higher doses were needed to induce such effects. NS-3 (0.1-0.3 mg/kg, i.v.) reversed the pentobarbital-induced narcosis in a dose-dependent manner. A similar effect was elicited by 30- to 100-fold higher doses of TRH than NS-3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8690305", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1275, "text": "Taken together with the finding that NS-3 did not bind to dopamine, adrenaline or muscarine receptors, it is suggested that NS-3 may restore the disturbance of consciousness by activating the brain dopamine, noradrenaline and acetylcholine neurons without stimulating these receptors directly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8690305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "A 46-year-old female motorcyclist, who suffered injuries to the brain stem in a traffic accident, showed hypotensive and bradycardiac responses to thyrotropin-releasing hormone (TRH) given to counter consciousness disturbance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1394244", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 697, "text": "The direct TRH (thyrotropin releasing hormone) stimulation to the anterior lobe was responded to well. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1317658", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1853, "text": "The neuropharmacological activities of TRH include an interesting arousal effect and an analeptic action on generalized depression of the CNS whether this depression is of natural origin, such as hibernation, or induced pharmacologically (barbiturates, ethanol) or of a traumatic origin (coma). This analeptic action is attributable to stimulation of cholinergic neurons in the septo-hippocampal area and to the presence of terminals containing TRH in the lateral septum and TRH receptors concentrated especially in the medial septum and diagonal band of Broca. It has also been suggested that TRH localized in the pineal gland has a part in activating the neuronal mechanisms of arousal. Associated with the arousal effect and especially evident in variously originated shock conditions are the activating effects of TRH on vegetative functions (body temperature, circulation, the gastrointestinal tract). These stimulatory activities on the CNS were the rationale for therapeutic use of TRH in the initial treatment of coma due to brain trauma and for the treatment of endogenous depression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2127684", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 879, "text": "In the vegetative group, TRH caused significant increases in MBP (from 91 +/- 8 mm Hg to 110 +/- 10 mm Hg) at 2 min after the injection [p < 0.05, analysis of variance (ANOVA) with a Scheff\u00e9 F-test]. In contrast, five of the seven BD patient showed no alterations in the measured parameter in response to the TRH injection. However, the remaining two BD patients, who had spinal reflexes, exhibited an elevation in MBP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8221703", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1362, "text": "These results indicate that in comatose patients, the hemodynamic effects of TRH may differ depending on impairments in the central nervous system; the results support previous reports indicating a mediation of the central sympathetic nervous system in the development of pressor effects of TRH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8221703", "endSection": "abstract" } ] }, { "body": "Do Conserved noncoding elements act as enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18047696", "http://www.ncbi.nlm.nih.gov/pubmed/21629789", "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "http://www.ncbi.nlm.nih.gov/pubmed/19782672", "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "http://www.ncbi.nlm.nih.gov/pubmed/18562680", "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "http://www.ncbi.nlm.nih.gov/pubmed/21047394", "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "http://www.ncbi.nlm.nih.gov/pubmed/17940009", "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "http://www.ncbi.nlm.nih.gov/pubmed/17210927", "http://www.ncbi.nlm.nih.gov/pubmed/15859353", "http://www.ncbi.nlm.nih.gov/pubmed/20494938", "http://www.ncbi.nlm.nih.gov/pubmed/19704032", "http://www.ncbi.nlm.nih.gov/pubmed/19171877", "http://www.ncbi.nlm.nih.gov/pubmed/19073165" ], "ideal_answer": [ "An important percentage of noncoding elements conserved across distant species shows enhancer activity and other forms of regulatory functionality." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0035326", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026801", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017124", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004742" ], "type": "yesno", "id": "5139ec51bee46bd34c000006", "snippets": [ { "offsetInBeginSection": 1169, "offsetInEndSection": 1216, "text": "The aCNEs are rich in tissue-specific enhancers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "endSection": "sections.0" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1483, "text": "Transgenic zebrafish assay of some human CNE enhancers that have been lost in teleosts", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20494938", "endSection": "sections.0" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1727, "text": "In all four cases where the zebra fish and human CNE display a similar expression pattern in zebra fish, the human CNE also displays a similar expression pattern in mouse. This suggests that the endogenous enhancer activity of \u223c30% of human CNEs can be determined from experiments in zebra fish", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20494938", "endSection": "sections.0" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1530, "text": "If these ancient CNEs are indeed enhancers directing tissue-specific expression of Hox genes, divergence of their sequences in vertebrate lineages might have led to altered expression patterns and presumably the functions of their associated Hox genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "endSection": "sections.0" }, { "offsetInBeginSection": 635, "offsetInEndSection": 887, "text": "Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805301", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Animal genomes possess highly conserved cis-regulatory sequences that are often found near genes that regulate transcription and development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704032", "endSection": "sections.0" }, { "offsetInBeginSection": 755, "offsetInEndSection": 914, "text": "We test 42 of our PCNEs in transgenic zebrafish assays--including examples from vertebrates and amphioxus--and find that the majority are functional enhancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704032", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs). CNEs cluster around genes that regulate development, and where tested, they can act as transcriptional enhancers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "endSection": "sections.0" }, { "offsetInBeginSection": 443, "offsetInEndSection": 1004, "text": ", we identified 17 highly conserved noncoding elements, 9 of which revealed specific acetylation marks in chromatin-immunoprecipitation and microarray (ChIP-chip) assays performed across 250 kb of the Lmo2 locus in 11 cell types covering different stages of hematopoietic differentiation. All candidate regulatory regions were tested in transgenic mice. An extended LMO2 proximal promoter fragment displayed strong endothelial activity, while the distal promoter showed weak forebrain activity. Eight of the 15 distal candidate elements functioned as enhancers,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19171877", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "sections.0" }, { "offsetInBeginSection": 585, "offsetInEndSection": 677, "text": "HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "sections.0" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1165, "text": "several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18562680", "endSection": "sections.0" }, { "offsetInBeginSection": 382, "offsetInEndSection": 463, "text": "We recently described GRBs in vertebrates, where most HCNEs function as enhancers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "endSection": "sections.0" }, { "offsetInBeginSection": 688, "offsetInEndSection": 762, "text": "Besides developmental regulators that are likely targets of HCNE enhancers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "endSection": "sections.0" }, { "offsetInBeginSection": 144, "offsetInEndSection": 734, "text": "We identify and characterize highly conserved noncoding elements flanking the TNF gene, which undergo activation-dependent intrachromosomal interactions. These elements, hypersensitive site (HSS)-9 and HSS+3 (9 kb upstream and 3 kb downstream of the TNF gene, respectively), contain DNase I hypersensitive sites in naive, T helper 1, and T helper 2 primary T cells. Both HSS-9 and HSS+3 inducibly associate with acetylated histones, indicative of chromatin remodeling, bind the transcription factor nuclear factor of activated T cells (NFAT)p in vitro and in vivo, and function as enhancers", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17940009", "endSection": "sections.0" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1420, "text": "We used the sequence signatures identified by this approach to successfully assign tissue-specific predictions to approximately 328,000 human-mouse conserved noncoding elements in the human genome. By overlapping these genome-wide predictions with a data set of enhancers validated in vivo, in transgenic mice, we were able to confirm our results with a 28% sensitivity and 50% precision.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17210927", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "endSection": "sections.0" }, { "offsetInBeginSection": 749, "offsetInEndSection": 1016, "text": "uncovered two anciently conserved noncoding sequences (CNS) upstream of COUP-TFII (CNS-62kb and CNS-66kb). Testing these two elements using reporter constructs in liver cells (HepG2) revealed that CNS-66kb, but not CNS-62kb, yielded robust in vitro enhancer activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15859353", "endSection": "sections.0" } ] }, { "body": "Can the iPS cell technology be used in Fanconi anemia therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20224565", "http://www.ncbi.nlm.nih.gov/pubmed/19483674" ], "ideal_answer": [ "iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications in Fanconi anemia." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057026", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064987", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "yesno", "id": "54edef0594afd6150400000d", "snippets": [ { "offsetInBeginSection": 309, "offsetInEndSection": 507, "text": "We explain a protocol for the reproducible generation of genetically corrected iPSCs starting from the skin biopsies of Fanconi anemia patients using retroviral transduction with OCT4, SOX2 and KLF4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20224565", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 645, "text": "Before reprogramming, the fibroblasts and/or keratinocytes of the patients are genetically corrected with lentiviruses expressing FANCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20224565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19483674", "endSection": "title" }, { "offsetInBeginSection": 322, "offsetInEndSection": 610, "text": "Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19483674", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 823, "text": "Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19483674", "endSection": "abstract" } ] }, { "body": "Which drug is considered as the first line treatment of fibromyalgia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23235657", "http://www.ncbi.nlm.nih.gov/pubmed/18840008", "http://www.ncbi.nlm.nih.gov/pubmed/21975791", "http://www.ncbi.nlm.nih.gov/pubmed/17653994" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": 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"beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653994", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 353, "text": "A multidisciplinary program was developed and implemented for patients with fibromyalgia in the primary care setting. The program included education (seven sessions) and physical therapy (25 sessions).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Amitriptyline for neuropathic pain and fibromyalgia in adults.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23235657", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 194, "text": "Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage) and fibromyalgia, and is recommended in many guidelines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23235657", "endSection": "abstract" }, { "offsetInBeginSection": 3926, "offsetInEndSection": 4099, "text": "Amitriptyline should continue to be used as part of the treatment of neuropathic pain or fibromyalgia, but only a minority of patients will achieve satisfactory pain relief.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23235657", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 210, "text": "Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they are not licensed for this use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21975791", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Oral pregabalin, a calcium channel alpha(2)delta-subunit ligand with analgesic, anxiolytic and antiepileptic activity, has shown efficacy in the treatment of fibromyalgia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18840008", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 939, "text": "Pregabalin is, therefore, a valuable option in the first-line treatment of patients with fibromyalgia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18840008", "endSection": "abstract" } ] }, { "body": "What are the signatures of aggressive periodontitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15154918", "http://www.ncbi.nlm.nih.gov/pubmed/18980520" ], "ideal_answer": [ "Aggressive periodontitis does not differ from chronic periodontitis from a microbial profile point of view but there are distinctive immunological signatures, including a higher expression in IgG against most periodontal pathogens and a more intense regulatory mechanism of metabolic processes." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:824", "http://www.disease-ontology.org/api/metadata/DOID:1474" ], "type": "summary", "id": "5544da8f5beec11c10000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1486, "text": "This pilot study examined gene expression signatures in pathological gingival tissues of subjects with chronic or aggressive periodontitis, and explored whether new subclasses of periodontitis can be identified based on gene expression profiles. A total of 14 patients, seven with chronic and seven with aggressive periodontitis, were examined with respect to clinical periodontal status, composition of subgingival bacterial plaque assessed by checkerboard hybridizations, and levels of serum IgG antibodies to periodontal bacteria assayed by checkerboard immunoblotting. In addition, at least two pathological pockets/patient were biopsied, processed for RNA extraction, amplification and labeling, and used to study gene expression using Affymetrix U-133 A arrays. Based on a total of 35 microarrays, no significantly different gene expression profiles appeared to emerge between chronic and aggressive periodontitis. However, a de novo grouping of the 14 subjects into two fairly robust clusters was possible based on similarities in gene expression. These two groups had similar clinical periodontal status and subgingival bacterial profiles, but differed significantly with respect to serum IgG levels against the important periodontal pathogens Porphyromonas gingivalis, Tannerella forsythensis and Campylobacter rectus. These early data point to the usefulness of gene expression profiling techniques in the identification of subclasses of periodontitis with common pathobiology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15154918", "endSection": "abstract" }, { "offsetInBeginSection": 1546, "offsetInEndSection": 1782, "text": "Gene ontology analysis identified 61 differentially expressed groups (adjusted P <0.05), including apoptosis, antimicrobial humoral response, antigen presentation, regulation of metabolic processes, signal transduction, and angiogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18980520", "endSection": "abstract" } ] }, { "body": "With which complexes is the protein SUS1 associated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24509845", "http://www.ncbi.nlm.nih.gov/pubmed/20395473", "http://www.ncbi.nlm.nih.gov/pubmed/20434206", "http://www.ncbi.nlm.nih.gov/pubmed/20230609", "http://www.ncbi.nlm.nih.gov/pubmed/22499857", "http://www.ncbi.nlm.nih.gov/pubmed/25526805", "http://www.ncbi.nlm.nih.gov/pubmed/21749979", "http://www.ncbi.nlm.nih.gov/pubmed/24705649", "http://www.ncbi.nlm.nih.gov/pubmed/22771212", "http://www.ncbi.nlm.nih.gov/pubmed/20007317", "http://www.ncbi.nlm.nih.gov/pubmed/23599000" ], "triples": [ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B4UN38", "o": "http://linkedlifedata.com/resource/#_4234554E3338005" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/B4UN38", "o": "http://linkedlifedata.com/resource/#_4234554E3338004" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4234554E3338005", "o": "SUS1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4234554E3338004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B5RSM1", "o": "http://linkedlifedata.com/resource/#_423552534D31005" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_423552534D31005", "o": "SUS1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/B5RSM1", "o": "http://linkedlifedata.com/resource/#_423552534D31004" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423552534D31004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q5KHW5", "o": "http://linkedlifedata.com/resource/#_51354B485735007" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51354B485735007", "o": "SUS1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q5KHW5", "o": "http://linkedlifedata.com/resource/#_51354B485735006" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51354B485735006", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q6BMU6", "o": "http://linkedlifedata.com/resource/#_5136424D5536005" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5136424D5536005", "o": "SUS1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136424D5536004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q6BMU6", "o": "http://linkedlifedata.com/resource/#_5136424D5536004" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q6CVU7", "o": "http://linkedlifedata.com/resource/#_513643565537005" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513643565537005", "o": "SUS1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513643565537004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q6CVU7", "o": "http://linkedlifedata.com/resource/#_513643565537004" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q75BB0", "o": "http://linkedlifedata.com/resource/#_513735424230005" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q75BB0", "o": "http://linkedlifedata.com/resource/#_513735424230004" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513735424230005", "o": "SUS1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513735424230004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q7LL15", "o": "true" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51374C4C3135004", "o": "Protein sus1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q7LL15", "o": "http://linkedlifedata.com/resource/#_51374C4C3135004" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/A5DG59", "o": "true" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413544473539004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/A5DG59", "o": "http://linkedlifedata.com/resource/#_413544473539004" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/A5E092", "o": "true" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413545303932004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/A5E092", "o": "http://linkedlifedata.com/resource/#_413545303932004" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/A6ZL57", "o": "true" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_41365A4C3537004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/A6ZL57", "o": "http://linkedlifedata.com/resource/#_41365A4C3537004" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/B3LN41", "o": "true" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/B3LN41", "o": "http://linkedlifedata.com/resource/#_42334C4E3431005" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42334C4E3431005", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/B4UN38", "o": "true" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/B5RSM1", "o": "true" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q5ADP6", "o": "true" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q5ADP6", "o": "http://linkedlifedata.com/resource/#_513541445036004" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513541445036004", "o": "Protein SUS1" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q5KHW5", "o": "true" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q6BMU6", "o": "true" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q6CVU7", "o": "true" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q75BB0", "o": "true" } ], "ideal_answer": [ "Sus1/ENY2 is a component of the SAGA and TREX-2 complexes" ], "exact_answer": [ [ "SAGA complex" ], [ "TREX-2 complex" ] ], "type": "list", "id": "56b773a96e3f8eaf4c000003", "snippets": [ { "offsetInBeginSection": 223, "offsetInEndSection": 373, "text": "The yeast DUBm comprises a catalytic subunit, Ubp8, and three additional subunits, Sgf11, Sus1 and Sgf73, all of which are required for DUBm activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25526805", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 337, "text": "the deubiquitination module (DUBm) of SAGA, which is composed of Ubp8, Sus1, Sgf11, and Sgf73.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24509845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The conserved Sac3:Thp1:Sem1:Sus1:Cdc31 (TREX2) complex binds to nuclear pore complexes (NPCs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705649", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 295, "text": "Sus1 (hENY2) participates in this coordination as part of two protein complexes: SAGA, a transcriptional co-activator; TREX-2, which functions in mRNA biogenesis and export.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23599000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The deubiquitinating module (DUBm) of the SAGA coactivator contains the Ubp8 isopeptidase, Sgf11, Sus1, and Sgf73, which form a highly interconnected complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22771212", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 193, "text": "Sus1/ENY2, a component of the SAGA and TREX-2 complexes, is involved in both transcription and mRNA export", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749979", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 307, "text": "Sus1 is a component of both the SAGA transcriptional co-activator complex and the TREX-2 complex that binds to nuclear pore complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20007317", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 388, "text": " distinct subcomplex called the deubiquitinating module (DUBm), which contains the ubiquitin-specific protease Ubp8, bound to Sgf11, Sus1, and Sgf73.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20395473", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 431, "text": "The yeast deubiquitinase Ubp8 protein is recruited and activated by the SAGA complex and, together with Sgf11, Sus1, and Sgf73, forms a DUB module responsible for deubiquitinating histone H2B during gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20434206", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 443, "text": "In the nucleus, Sus1 is associated to the transcriptional co-activator SAGA and to the NPC associated complex termed TREX2/THSC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20230609", "endSection": "abstract" } ] }, { "body": "Can Preimplantation Genetic Diagnosis (PGD) be used for gender selection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19294755", "http://www.ncbi.nlm.nih.gov/pubmed/12470342", "http://www.ncbi.nlm.nih.gov/pubmed/20102489", "http://www.ncbi.nlm.nih.gov/pubmed/19251775", "http://www.ncbi.nlm.nih.gov/pubmed/18829009", "http://www.ncbi.nlm.nih.gov/pubmed/20638568", "http://www.ncbi.nlm.nih.gov/pubmed/18222917", "http://www.ncbi.nlm.nih.gov/pubmed/9329835", "http://www.ncbi.nlm.nih.gov/pubmed/12615807", "http://www.ncbi.nlm.nih.gov/pubmed/19891844", "http://www.ncbi.nlm.nih.gov/pubmed/18667646" ], "ideal_answer": [ "Preimplantation Genetic Diagnosis can be used for gender selection." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012743", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005783", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019836" ], "type": "yesno", "id": "52b2ed144003448f55000004", "snippets": [ { "offsetInBeginSection": 96, "offsetInEndSection": 390, "text": "This testing is used for identifying singlegene disorders, chromosomal abnormalities, mitochondrial disorders, gender selection in non-mendelian disorders with unequal gender distribution, aneuploidy screening, and other preconceptually identified genetic abnormalities in prospective parents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20638568", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 289, "text": " Although many clinics offer PGD for HA by gender selection, an approach that detects the presence of the underlying F8 mutation has several advantages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20102489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 719, "text": "Preimplantation genetic diagnosis (PGD) for gender selection for non-medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis that it could disrupt the sex ratio, that it discriminates against women and that it leads to disposal of normal embryos of the non-desired gender. In this study, the analysis of a large series of PGD procedures for gender selection from a wide geographical area in the USA shows that, in general, there is no deviation in preference towards any specific gender except for a preference of males in some ethnic populations of Chinese, Indian and Middle Eastern origin that represent a small percentage of the US population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19891844", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1111, "text": " In response to one specific question, one-third of the couples agreed to use the donor child as a lifetime organ donor and supported the use of PGD for non-medical gender selection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19294755", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 455, "text": "More specifically, I illustrate how the prescriptions of deliberative democracy can be applied to the issue of regulating non-medical uses of pre-implantation genetic diagnosis (PGD), such as gender selection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19251775", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1124, "text": "Private clinics were more likely than other programs to be on either the East or West Coast, list certain PGD risks (e.g., diagnostic error), note that PGD was new or controversial, reference source of PGD information, provide accuracy rates of genetic testing of embryos, and offer gender selection for social reasons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18829009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 552, "text": "The purpose of this article is to ascertain and appraise the ethical issues inherent to the utilisation of preimplantation genetic diagnosis for gender selection in infertile patients anticipating undergoing a medically indicated assisted reproductive technique procedure. Performance of preimplantation genetic diagnosis per request specifically for gender selection by an infertile couple undergoing medically indicated assisted reproductive technique may not breach the principles of ethics, and is unlikely to alter the population balance of sexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18667646", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 653, "text": "One possible use of PGD is to perform gender selection for couples whose offspring are at increased risk of disorders that do not follow Mendelian inheritance, but which are substantially more common in one sex than another (unequal sex incidence). Here, we examine the clinical and ethical issues to be considered prior to offering PGD gender selection to reduce the risk of a child being affected by a non-Mendelian condition with unequal sex incidence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18222917", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 301, "text": "New uses of PGD have been reported in the past year for screening embryos for susceptibility to cancer, for late-onset diseases, for HLA-matching for existing children, and for gender. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615807", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 708, "text": "This article describes current and likely future uses of PGD, and then analyses the ethical issues posed by new uses of PGD to screen embryos for susceptibility and late-onset conditions, for HLA-matching for tissue donation to an existing child, and for gender selection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "The use of PGD for sex selection arouses considerable debate, especially in countries like India that have a marked cultural preference for boys. It is argued that using PGD for sex selection is a treatment option that can be ethically offered to couples who desire to use this technology to plan their families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12470342", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 785, "text": "Another concern is the use of this technology for nongenetic disorders such as gender selection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9329835", "endSection": "abstract" } ] }, { "body": "What is the principle of ATAC (Assay for Transposase-Accessible Chromatin) technique?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25679813", "http://www.ncbi.nlm.nih.gov/pubmed/24097267" ], "ideal_answer": [ "ATAC-seq (Assay for Transposase-Accessible Chromatin) is an assay for transposase-accessible chromatin using sequencing, based on direct in vitro transposition of sequencing adaptors into native chromatin. ATAC is a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution.", "To this end, we first compare two different approaches to detect open chromatin in vivo using the Drosophila eye primordium as a model system: FAIRE-seq, based on physical separation of open versus closed chromatin; and ATAC-seq, based on preferential integration of a transposon into open chromatin. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. In conclusion, we show that FAIRE-seq and ATAC-seq based open chromatin profiling, combined with motif discovery, is a straightforward approach to identify functional genomic regulatory regions, master regulators, and gene regulatory networks controlling complex in vivo processes. We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis.", "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis " ], "concepts": [ "http://www.uniprot.org/uniprot/TRAT_AMIAI" ], "type": "summary", "id": "56ebee26107309bc2f000002", "snippets": [ { "offsetInBeginSection": 1892, "offsetInEndSection": 2173, "text": "In conclusion, we show that FAIRE-seq and ATAC-seq based open chromatin profiling, combined with motif discovery, is a straightforward approach to identify functional genomic regulatory regions, master regulators, and gene regulatory networks controlling complex in vivo processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25679813", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 839, "text": "To this end, we first compare two different approaches to detect open chromatin in vivo using the Drosophila eye primordium as a model system: FAIRE-seq, based on physical separation of open versus closed chromatin; and ATAC-seq, based on preferential integration of a transposon into open chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25679813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 501, "text": "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 840, "text": "Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 760, "text": "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 502, "text": "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" } ] }, { "body": "Which are the main NMD factors in Saccharomyces cerevisiae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22065998", "http://www.ncbi.nlm.nih.gov/pubmed/11073994", "http://www.ncbi.nlm.nih.gov/pubmed/22227378", "http://www.ncbi.nlm.nih.gov/pubmed/17705828", "http://www.ncbi.nlm.nih.gov/pubmed/11238889", "http://www.ncbi.nlm.nih.gov/pubmed/18087042", "http://www.ncbi.nlm.nih.gov/pubmed/22670525", "http://www.ncbi.nlm.nih.gov/pubmed/20675403", "http://www.ncbi.nlm.nih.gov/pubmed/11113196", "http://www.ncbi.nlm.nih.gov/pubmed/16043493", "http://www.ncbi.nlm.nih.gov/pubmed/16394582" ], "ideal_answer": [ "Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that accelerates the degradation of mRNAs containing premature translation termination codons. This quality control pathway depends on the NMD-specific factors, Upf1p, Upf2p/Nmd2p, and Upf3p, as well as the two release factors, eRF1 and eRF3 (respectively designated Sup45p and Sup35p in yeast). NMD activation is also enabled by the absence of the poly(A)-binding protein, Pab1p, downstream of a termination event", "In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs requires the three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p.", "In addition to their well-documented roles in the promotion of nonsense-mediated mRNA decay (NMD), yeast Upf proteins (Upf1, Upf2/Nmd2, and Upf3) also manifest translational regulatory functions, at least in vitro, including roles in premature translation termination and subsequent reinitiation" ], "exact_answer": [ [ "Upf1p" ], [ "Nmd2p" ], [ "Upf3p" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012441", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000184" ], "type": "list", "id": "5516757c46478f2f2c000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "In addition to their well-documented roles in the promotion of nonsense-mediated mRNA decay (NMD), yeast Upf proteins (Upf1, Upf2/Nmd2, and Upf3) also manifest translational regulatory functions, at least in vitro, including roles in premature translation termination and subsequent reinitiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20675403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 377, "text": "In Saccharomyces cerevisiae, nonsense-mediated mRNA decay (NMD) requires Upf1p, Upf2p, and Upf3p to accelerate the decay rate of two unique classes of transcripts: (1) nonsense mRNAs that arise through errors in gene expression, and (2) naturally occurring transcripts that lack coding errors but have built-in features that target them for accelerated decay (error-free mRNAs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16043493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs requires the decapping enzyme Dcp1p, the 5'-to-3' exoribonuclease Xrn1p, and the three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11238889", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 641, "text": "Our results indicate that Upf1p, Nmd2p, and Upf3p regulate decapping and exonucleolytic degradation of nonsense-containing mRNAs. In addition, we show that these factors also regulate the same processes in the degradation of wild-type mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11238889", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 357, "text": "This quality control pathway depends on the NMD-specific factors, Upf1p, Upf2p/Nmd2p, and Upf3p, as well as the two release factors, eRF1 and eRF3 (respectively designated Sup45p and Sup35p in yeast)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22227378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "In addition to their well-documented roles in the promotion of nonsense-mediated mRNA decay (NMD), yeast Upf proteins (Upf1, Upf2/Nmd2, and Upf3) also manifest translational regulatory functions, at least in vitro, including roles in premature translation termination and subsequent reinitiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20675403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Association of yeast Upf1p with direct substrates of the NMD pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18087042", "endSection": "title" }, { "offsetInBeginSection": 283, "offsetInEndSection": 525, "text": " Translation termination factors eRF1 (Sup45) and eRF3 (Sup35) participate not only in the last step of protein synthesis but also in mRNA degradation and translation initiation via interaction with such proteins as Pab1, Upf1, Upf2 and Upf3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17705828", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1145, "text": "From these results, we conclude that sup111, sup112 and sup113 are mutant alleles of UPF2, UPF3 and UPF1, respectively, and thus attribute suppressor activity of these mutations to defects in the NMD (nonsense-mediated mRNA decay) machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16394582", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "In Saccharomyces cerevisiae, nonsense-mediated mRNA decay (NMD) requires Upf1p, Upf2p, and Upf3p to accelerate the decay rate of two unique classes of transcripts: (1) nonsense mRNAs that arise through errors in gene expression, and (2) naturally occurring transcripts that lack coding errors but have built-in features that target them for accelerated decay (error-free mRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16043493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs requires the decapping enzyme Dcp1p, the 5'-to-3' exoribonuclease Xrn1p, and the three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11238889", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 699, "text": "To date, human (h) Upf1 protein (p) (hUpf1p), a group 1 RNA helicase named after its Saccharomyces cerevisiae orthologue that functions in both translation termination and NMD, has been the only factor shown to be required for NMD in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11113196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs requires the decapping enzyme Dcp1p, the 5-to-3 exoribonuclease Xrn1p, and the three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11238889", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 516, "text": "In Saccharomyces cerevisiae, three trans-acting factors (Upf1p to Upf3p) are required for NMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11073994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Interactions between Upf1 and the decapping factors Edc3 and Pat1 in Saccharomyces cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22065998", "endSection": "title" }, { "offsetInBeginSection": 163, "offsetInEndSection": 395, "text": "In yeast Saccharomyces cerevisiae, the activity of this pathway depends on the recognition of the PTC by the translational machinery and interaction of translation termination factors eRF1 and eRF3 with Upf1, Upf2 and Upf3 proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22670525", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 394, "text": "In yeast Saccharomyces cerevisiae, the activity of this pathway depends on the recognition of the PTC by the translational machinery and interaction of translation termination factors eRF1 and eRF3 with Upf1, Upf2 and Upf3 proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22670525", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 477, "text": "NMD activation is also enabled by the absence of the poly(A)-binding protein, Pab1p, downstream of a termination event", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22227378", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 302, "text": "Of those, a group of weak and recessive suppressors, sup111, sup112 and sup113, is of particular interest because of their dependency on [PSI+], a yeast prion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16394582", "endSection": "abstract" } ] }, { "body": "Which histone marks are deposited by Set7?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21963854", "http://www.ncbi.nlm.nih.gov/pubmed/15200950", "http://www.ncbi.nlm.nih.gov/pubmed/12086618", "http://www.ncbi.nlm.nih.gov/pubmed/12208845" ], "ideal_answer": [ "Set7 is H4K20 monomethyltransferase. Upregulation of PR-Set7 expression upon loss of HCF-1 leads to improper mitotic H4-K20 methylation. Set7 (or some variant) has also been reported to perform mono-methylation on lysine-4 of H3." ], "exact_answer": [ [ "H4K20 monomethylation" ], [ "H3K4 monomethylation" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011495", "http://www.uniprot.org/uniprot/SETD7_HALRO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042393", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016571", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016570" ], "type": "list", "id": "5160412d298dcd4e5100003c", "snippets": [ { "offsetInBeginSection": 190, "offsetInEndSection": 226, "text": "the loss of H4 lysine 20 methylation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086618", "endSection": "sections.0" }, { "offsetInBeginSection": 286, "offsetInEndSection": 351, "text": "Transcriptionally competent regions lack H4 lysine 20 methylation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086618", "endSection": "sections.0" }, { "offsetInBeginSection": 17, "offsetInEndSection": 102, "text": "a human histone H4 lysine 20 methyltransferase and cloned the encoding gene, PR/SET07", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086618", "endSection": "sections.0" }, { "offsetInBeginSection": 338, "offsetInEndSection": 433, "text": "Localization of PR-Set7 to mitotic chromosomes and subsequent increase in H4 Lys 20 methylation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12208845", "endSection": "sections.0" }, { "offsetInBeginSection": 698, "offsetInEndSection": 842, "text": "the H4-K20 methyltransferase PR-Set7. Indeed, upregulation of PR-Set7 expression upon loss of HCF-1 leads to improper mitotic H4-K20 methylation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15200950", "endSection": "sections.0" } ] }, { "body": "Has proteomics been used in the study of the dry eye syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21384922", "http://www.ncbi.nlm.nih.gov/pubmed/24282230", "http://www.ncbi.nlm.nih.gov/pubmed/19705875", "http://www.ncbi.nlm.nih.gov/pubmed/20882555", "http://www.ncbi.nlm.nih.gov/pubmed/23272196" ], "ideal_answer": [ "Yes, tears obtained from patients with the dry eye syndrome have been analyzed using different proteomic technologies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005128", "http://www.disease-ontology.org/api/metadata/DOID:5614", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.disease-ontology.org/api/metadata/DOID:10140", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005123", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005136" ], "type": "yesno", "id": "5322de919b2d7acc7e000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282230", "endSection": "title" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1636, "text": "Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282230", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 679, "text": " 2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23272196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Two dimensional electrophoretic analysis of human tears: collection method in dry eye syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20882555", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19705875", "endSection": "title" }, { "offsetInBeginSection": 1842, "offsetInEndSection": 1993, "text": "This study demonstrated that iTRAQ technology combined with 2D-nanoLC-nanoESI-MS/MS quantitative proteomics is a powerful tool for biomarker discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19705875", "endSection": "abstract" } ] }, { "body": "What is the indication for isradipine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8213473", "http://www.ncbi.nlm.nih.gov/pubmed/10728516", "http://www.ncbi.nlm.nih.gov/pubmed/8963604", "http://www.ncbi.nlm.nih.gov/pubmed/2150641", "http://www.ncbi.nlm.nih.gov/pubmed/15257873", "http://www.ncbi.nlm.nih.gov/pubmed/8466736", "http://www.ncbi.nlm.nih.gov/pubmed/7848351", "http://www.ncbi.nlm.nih.gov/pubmed/7918132", "http://www.ncbi.nlm.nih.gov/pubmed/14727944", "http://www.ncbi.nlm.nih.gov/pubmed/7738211", "http://www.ncbi.nlm.nih.gov/pubmed/7789292", "http://www.ncbi.nlm.nih.gov/pubmed/2523644", "http://www.ncbi.nlm.nih.gov/pubmed/2523646", "http://www.ncbi.nlm.nih.gov/pubmed/7921533", "http://www.ncbi.nlm.nih.gov/pubmed/7946181", "http://www.ncbi.nlm.nih.gov/pubmed/12215829", "http://www.ncbi.nlm.nih.gov/pubmed/9544865", "http://www.ncbi.nlm.nih.gov/pubmed/2137344", "http://www.ncbi.nlm.nih.gov/pubmed/11172743", "http://www.ncbi.nlm.nih.gov/pubmed/8205296", "http://www.ncbi.nlm.nih.gov/pubmed/2949585", "http://www.ncbi.nlm.nih.gov/pubmed/1363224", "http://www.ncbi.nlm.nih.gov/pubmed/7621840", "http://www.ncbi.nlm.nih.gov/pubmed/10854683", "http://www.ncbi.nlm.nih.gov/pubmed/7955262" ], "ideal_answer": [ "Isradipine is safe and effective when administered long-term in the treatment of hypertensive patients", "The calcium antagonist isradipine is used for hypertensive therapy." ], "exact_answer": [ "Hypertension" ], "concepts": [ "http://www.biosemantics.org/jochem#4250298", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006973", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017275", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4250298" ], "type": "factoid", "id": "56c3184050c68dd416000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "These are the preliminary data of an open multicenter trial of antihypertensive treatment with isradipine as monotherapy (dose, 4.55 +/- 0.56 mg twice daily; n = 11) or isradipine (7.5 +/- 0.63 mg twice daily) in combination with bopindolol (1.16 +/- 0.12 mg once daily; n = 30) administered for 3 years to patients with essential hypertension (WHO classification I or II). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7946181", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1138, "text": " It is concluded that isradipine is safe and effective when administered long-term in the treatment of hypertensive patients with either hyperlipidemia or NIDDM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7946181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Regression of left ventricular hypertrophy with isradipine antihypertensive therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8466736", "endSection": "title" }, { "offsetInBeginSection": 1584, "offsetInEndSection": 1827, "text": "Isradipine monotherapy was an effective antihypertensive drug in blacks with essential hypertension, resulting in regression of left ventricular wall thickness and mass and augmentation of fractional shortening per 100 g left ventricular mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2137344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "These are the preliminary data of an open multicenter trial of antihypertensive treatment with isradipine as monotherapy (dose, 4.55 +/- 0.56 mg twice daily; n = 11) or isradipine (7.5 +/- 0.63 mg twice daily) in combination with bopindolol (1.16 +/- 0.12 mg once daily; n = 30) administered for 3 years to patients with essential hypertension (WHO classification I or II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7946181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The antihypertensive effect of isradipine was studied in 45 patients with mild-to-moderate hypertension (mean age 59 years) using casual and ambulatory 24-h blood pressure measurement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8205296", "endSection": "abstract" }, { "offsetInBeginSection": 48, "offsetInEndSection": 84, "text": "isradipine antihypertensive therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8466736", "endSection": "title" }, { "offsetInBeginSection": 775, "offsetInEndSection": 810, "text": "isradipine antihypertensive therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8466736", "endSection": "abstract" }, { "offsetInBeginSection": 1584, "offsetInEndSection": 1646, "text": "Isradipine monotherapy was an effective antihypertensive drug ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2137344", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 912, "text": "Isradipine is cytoprotective after a stroke when used as an antihypertensive: at doses which normalise high blood pressure in spontaneously hypertensive rats, isradipine reduces by more than 60% the infarct size caused by a subsequent stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2150641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "[Long-term antihypertensive therapy with isradipine. Improvement of coronary flow reserve in patients with arterial hypertension and microvascular angina].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7848351", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "[Isradipine in arterial hypertension in motor vehicle drivers].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8963604", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Evaluation of the safety and efficacy of isradipine in elderly patients with essential hypertension. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2523644", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "A multicenter evaluation of the safety and efficacy of isradipine and atenolol in the treatment of hypertension. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2523646", "endSection": "title" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1367, "text": "it is advisable to be very careful in the use of isradipine as a therapy for hypertension and other indications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15257873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Calcium channel antagonists (CCAs) may either be divided into the dihydropyridines (e.g. amlodipine, felodipine, isradipine, lacidipine, nilvadipine, nifedipine, nicardipine etc.), t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14727944", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 374, "text": "In the past few years, however, several dihydropyridine calcium channel antagonists, including nicardipine, isradipine, felodipine, nimodipine, and amlodipine, have been marketed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8213473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The new calcium antagonist isradipine. Effect on blood pressure and the left ventricle in black hypertensive patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2137344", "endSection": "title" } ] }, { "body": "List non-surgical treatment modalities that are included in the Stupp protocol.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24111708", "http://www.ncbi.nlm.nih.gov/pubmed/23453151", "http://www.ncbi.nlm.nih.gov/pubmed/23254891", "http://www.ncbi.nlm.nih.gov/pubmed/23535992", "http://www.ncbi.nlm.nih.gov/pubmed/24600235", "http://www.ncbi.nlm.nih.gov/pubmed/22464950", "http://www.ncbi.nlm.nih.gov/pubmed/24287680", "http://www.ncbi.nlm.nih.gov/pubmed/22141608", "http://www.ncbi.nlm.nih.gov/pubmed/21156036", "http://www.ncbi.nlm.nih.gov/pubmed/23588276", "http://www.ncbi.nlm.nih.gov/pubmed/20428822", "http://www.ncbi.nlm.nih.gov/pubmed/25201633", "http://www.ncbi.nlm.nih.gov/pubmed/21344976", "http://www.ncbi.nlm.nih.gov/pubmed/18808066", "http://www.ncbi.nlm.nih.gov/pubmed/25434389", "http://www.ncbi.nlm.nih.gov/pubmed/24518393", "http://www.ncbi.nlm.nih.gov/pubmed/20045159", "http://www.ncbi.nlm.nih.gov/pubmed/20870254", "http://www.ncbi.nlm.nih.gov/pubmed/22359215" ], "ideal_answer": [ "Radiotherapy and chemotherapy are non-surgical treatment modalities that are included in the Stupp protocol. This protocol is widely used for treatment of glioblastoma." ], "exact_answer": [ [ "radiotherapy" ], [ "chemotherapy" ] ], "type": "list", "id": "54df6ed91388e8454a000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "OBJECTIVE: It is now accepted that the concomitant administration of temozolomide with radiotherapy (Stupp regime), in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM), significantly improves survival and this practice has been adopted locally since 2004.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24111708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "BACKGROUND: The introduction of ALA-Fluorescence-guided surgery (FGS) followed by concomitant radiochemotherapy according to the Stupp-protocol is representative of the major changes in glioblastoma therapy in the past years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23588276", "endSection": "abstract" }, { "offsetInBeginSection": 1485, "offsetInEndSection": 1641, "text": "CONCLUSIONS: FGS and radiochemotherapy according to the Stupp protocol have induced an impressive improvement in overall survival in glioblastoma patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23588276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "Current treatment strategies in patients with newly-diagnosed glioblastoma include surgical resection with post-operative radiotherapy and concomitant/adjuvant temozolomide (the \"Stupp protocol\") or resection with implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the surgical cavity followed by radiotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23535992", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 345, "text": "The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23453151", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 508, "text": "PATIENTS AND METHODS: A total of 191 patients with primary GBM were postoperatively treated with either radiation and concomitant TMZ, followed by adjuvant TMZ (Stupp protocol) (n = 154), or radiation followed by adjuvant TMZ (n = 37).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23254891", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 935, "text": "Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434389", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 228, "text": "The treatment of glioblastoma includes surgery followed by chemoradiation with the protocol of Stupp et al. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25201633", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 1043, "text": "Since the publication of a study by Stupp et al in 2005, which used a protocol of conventional fractionated irradiation with concomitant TMZ followed by standard TMZ for six cycles, many clinical studies in the People's Republic of China have demonstrated that such a treatment strategy has significantly improved efficacy with limited side effects for newly diagnosed glioblastoma after surgery as compared with strategies that do not contain TMZ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24600235", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 739, "text": "Standard chemoradiotherapy as per the Stupp protocol, together with multimodal rehabilitation, resulted in substantial functional improvement within 6 weeks of initiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24518393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "BACKGROUND: Patients with glioblastoma treated with BCNU wafer implantation for recurrence frequently receive frontline chemoradiotherapy with temozolomide as part of the Stupp protocol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24287680", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 244, "text": "This is followed by concurrent radio-chemotherapy with temozolomide (TMZ) according to the Stupp protocol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22464950", "endSection": "abstract" }, { "offsetInBeginSection": 1718, "offsetInEndSection": 2045, "text": "CONCLUSIONS: MGMT promoter methylation status and low MGMT expression both were identified as positive prognosticators in patients with newly diagnosed glioblastoma who underwent surgical resection and received Gliadel wafer implants followed by adjuvant radiotherapy and concomitant oral TMZ chemotherapy (the Stupp protocol).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22359215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "INTRODUCTION: To evaluate the incidence and impact of early post-chemoradiation (cRT) 'pseudoprogression' (PsPD) amongst glioblastoma multiforme (GBM) patients treated with the current standard of care - 60 Gy conformal radiotherapy with concurrent low-dose temozolomide, followed by six cycles of high-dose temozolomide (the 'Stupp protocol'). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22141608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "In patients with glioblastoma multiforme (GBM), there is no consensus on the sequential use of two existing regimens: post-operative Gliadel implantation into the surgical cavity and concomitant temozolomide with radiotherapy followed by adjuvant temozolomide ('Stupp protocol'). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21344976", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 727, "text": "We also screened for associations between the level of methylation of CpG sites and overall survival in a cohort of 50 patients uniformly treated by surgery, radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21156036", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 777, "text": "Surprisingly, less than half the patients having surgery received concomitant radiochemotherapy according to the Stupp protocol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20870254", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 578, "text": "We analyzed MGMT methylation by methylation-specific PCR in 90 GBM patients from four Portuguese hospitals, uniformly treated with radiotherapy combined with concomitant and adjuvant temozolomide (Stupp protocol).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20428822", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 296, "text": "The current care standards for newly diagnosed glioblastoma consist, when feasible, in surgical resection, radiotherapy, and chemotherapy, as described in the Stupp protocol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20045159", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 400, "text": "Moreover, there are no data concerning the effect of concomitant radiochemotherapy according to the STUPP protocol on the course ofMS in patients with coexisting glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18808066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Current treatment strategies in patients with newly-diagnosed glioblastoma include surgical resection with post-operative radiotherapy and concomitant/adjuvant temozolomide (the \"Stupp protocol\") or resection with implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the surgical cavity followed by radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23535992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "Current treatment strategies in patients with newly-diagnosed glioblastoma include surgical resection with post-operative radiotherapy and concomitant/adjuvant temozolomide (the \"Stupp protocol\") or resection with implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the surgical cavity followed by radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23535992", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 331, "text": "The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23453151", "endSection": "abstract" } ] }, { "body": "Which genes are associated with Ehlers-Danlos syndrome type I/II?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10796876", "http://www.ncbi.nlm.nih.gov/pubmed/8923000", "http://www.ncbi.nlm.nih.gov/pubmed/8541855", "http://www.ncbi.nlm.nih.gov/pubmed/9425231", "http://www.ncbi.nlm.nih.gov/pubmed/8752669", "http://www.ncbi.nlm.nih.gov/pubmed/9783710", "http://www.ncbi.nlm.nih.gov/pubmed/12145749", "http://www.ncbi.nlm.nih.gov/pubmed/9499606", "http://www.ncbi.nlm.nih.gov/pubmed/20847697" ], "ideal_answer": [ "It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the \u03b11 and the \u03b12-chain of type V collagen, respectively", "Ehlers-Danlos syndrome (EDS) type I (the classical variety) is a dominantly inherited, genetically heterogeneous connective-tissue disorder. Mutations in the COL5A1 and COL5A2 genes, which encode type V collagen, have been identified in several individuals. Most mutations affect either the triple-helical domain of the protein or the expression of one COL5A1 allele It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the \u03b11 and the \u03b12-chain of type V collagen, respectively ", "It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the \u03b11 and the \u03b12-chain of type V collagen, respectively.", "Ehlers-Danlos syndrome (EDS) type I (the classical variety) is a dominantly inherited, genetically heterogeneous connective-tissue disorder. Mutations in the COL5A1 and COL5A2 genes, which encode type V collagen, have been identified in several individuals. Most mutations affect either the triple-helical domain of the protein or the expression of one COL5A1 allele " ], "exact_answer": [ [ "COL5A1" ], [ "COL5A2" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14720", "http://www.disease-ontology.org/api/metadata/DOID:13359" ], "type": "list", "id": "54e22b62ae9738404b000011", "snippets": [ { "offsetInBeginSection": 437, "offsetInEndSection": 675, "text": "It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the \u03b11 and the \u03b12-chain of type V collagen, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20847697", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1176, "text": "In the majority of patients with molecularly characterized classic Ehlers-Danlos syndrome, the disease is caused by a mutation leading to a nonfunctional COL5A1 allele and resulting in haploinsufficiency of type V collagen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20847697", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1335, "text": "A smaller proportion of patients harbor a structural mutation in COL5A1 or COL5A2, causing the production of a functionally defective type V collagen protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20847697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha1(V) N-propeptides and Ehlers-Danlos syndrome type I", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12145749", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Ehlers-Danlos syndrome (EDS) type I (the classical variety) is a dominantly inherited, genetically heterogeneous connective-tissue disorder. Mutations in the COL5A1 and COL5A2 genes, which encode type V collagen, have been identified in several individuals. Most mutations affect either the triple-helical domain of the protein or the expression of one COL5A1 allele", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12145749", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 506, "text": "We identified a novel splice-acceptor mutation (IVS4-2A-->G) in the N-propeptide-encoding region of COL5A1, in one patient with EDS type I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12145749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Mutations of the alpha2(V) chain of type V collagen impair matrix assembly and produce ehlers-danlos syndrome type I", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9425231", "endSection": "title" }, { "offsetInBeginSection": 169, "offsetInEndSection": 332, "text": "We have identified mutations of the COL5A2 gene, which encodes the alpha2(V) chain of type V collagen, in two unrelated patients with the severe type I form of EDS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9425231", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1183, "text": "Our findings show that heterozygous mutations of the COL5A2 gene can produce the EDS type I phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9425231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro alpha 1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8923000", "endSection": "title" }, { "offsetInBeginSection": 267, "offsetInEndSection": 449, "text": "We report that genomic polymorphisms at the pro alpha 1(V) gene (COL5A1) locus cosegregated with the gravis form of Ehlers-Danlos syndrome (EDS) (type I) in a three generation family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8923000", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 965, "text": "Since exon 65 encodes 78 residues of the carboxyl propeptide, the expected result of this mutation is reduced efficiency in incorporating mutant pro alpha 1(V) chains into type V collagen molecules and reduced type V collagen synthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8923000", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1052, "text": "These studies indicate that heterozygous mutations in COL5A1 can result in EDS type I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8923000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "The gene encoding collagen alpha1(V)(COL5A1) is linked to mixed Ehlers-Danlos syndrome type I/II", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8752669", "endSection": "title" }, { "offsetInBeginSection": 386, "offsetInEndSection": 552, "text": "Recently, genetic linkage has been demonstrated between the COL5A1 gene, which encodes the alphal chain of type V collagen, and EDS type II in a large British kindred", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8752669", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 707, "text": "Using a polymorphic intragenic simple sequence repeat at the COL5A1 locus, we now demonstrate tight linkage to EDS type I/II in a three-generation family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8752669", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 974, "text": "The variation in expression in this family suggests that EDS types I and II are allelic, and the linkage data support the hypothesis that mutation in COL5A1 can cause both phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8752669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10796876", "endSection": "title" }, { "offsetInBeginSection": 85, "offsetInEndSection": 230, "text": "Recently mutations have been found in the genes for type V collagen in a small number of people with the most common forms of EDS, types I and II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9783710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "The gene encoding collagen alpha1(V)(COL5A1) is linked to mixed Ehlers-Danlos syndrome type I/II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8752669", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8541855", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Genetic linkage to the collagen alpha 1 (V) gene (COL5A1) in two British Ehlers-Danlos syndrome families with variable type I and II phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9499606", "endSection": "title" } ] }, { "body": "Which factors are considered in the ABCD2 score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21646462", "http://www.ncbi.nlm.nih.gov/pubmed/21554497", "http://www.ncbi.nlm.nih.gov/pubmed/23983858", "http://www.ncbi.nlm.nih.gov/pubmed/23683740", "http://www.ncbi.nlm.nih.gov/pubmed/22237056", "http://www.ncbi.nlm.nih.gov/pubmed/21388829", "http://www.ncbi.nlm.nih.gov/pubmed/20582954", "http://www.ncbi.nlm.nih.gov/pubmed/19803400", "http://www.ncbi.nlm.nih.gov/pubmed/19556026", "http://www.ncbi.nlm.nih.gov/pubmed/20421579", "http://www.ncbi.nlm.nih.gov/pubmed/23871489" ], "ideal_answer": [ "Age, Blood pressure, Clinical features, Duration of symptoms and Diabetes are included in the ABCD2 score, which is used to identify patients having a transient ischemic attack who are at high risk for imminent stroke." ], "exact_answer": [ [ "Age" ], [ "Blood pressure" ], [ "Clinical features" ], [ "Duration of symptoms" ], [ "Diabetes" ] ], "type": "list", "id": "551adceb622b194345000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "The 'accuracy' of age, blood pressure, clinical features, duration and diabetes (ABCD(2)) scoring by non-stroke specialists referring patients to a daily Rapid Access Stroke Prevention (RASP) service is unclear, as is the accuracy of ABCD(2) scoring by trainee residents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23871489", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 694, "text": " Classification of low risk was based on an age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score <4 and the absence of high risk features, including known carotid disease, crescendo TIA, or atrial fibrillation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23683740", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 669, "text": "Our goal was to compare the very early predictive accuracy of the most relevant clinical scores [age, blood pressure, clinical features and duration of symptoms (ABCD) score, ABCD and diabetes (ABCD2) score, ABCD and brain infarction on imaging score, ABCD2 and brain infarction on imaging score, ABCD and prior TIA within 1 week of the index event (ABCD3) score, California Risk Score, Essen Stroke Risk Score and Stroke Prognosis Instrument II] in consecutive transient ischemic attack (TIA) patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237056", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 374, "text": "We examined the association of the age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score, a validated risk prediction model for stroke after TIA, and the presence of ICS or ECS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "BACKGROUND: The ABCD2 score (Age, Blood pressure, Clinical features, Duration of symptoms and Diabetes) is used to identify patients having a transient ischemic attack who are at high risk for imminent stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21646462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "BACKGROUND AND PURPOSE: The risk of stroke after a transient ischaemic attack (TIA) can be predicted by scores incorporating age, blood pressure, clinical features, duration (ABCD-score), and diabetes (ABCD2-score). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "BACKGROUND: Modifications to the age, blood pressure, clinical symptoms, duration of symptoms, and diabetes (ABCD2) score, which incorporate history of hypertension and acute hyperglycemia in addition to acute blood pressure (BP) elevation and history of diabetes, have been proposed to increase the predictive value of the score. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21388829", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 322, "text": "ABCD2 (Age, Blood pressure, Clinical features, Duration, Diabetes) score and magnetic resonance imaging abnormalities help to identify patients at high risk of stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20582954", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 835, "text": "METHODS: We prospectively calculated the ABCD(2) score (age [> or = 60 years: 1 point]; blood pressure [systolic >140 mm Hg or diastolic >90 mm Hg: 1[; clinical features [unilateral weakness: 2, speech disturbance without weakness: 1, other symptom: 0]; duration of symptoms [ <10 minutes: 0, 10-59 minutes: 1, > or = 60 minutes: 2]; diabetes mellitus [yes: 1]) in consecutive TIA patients hospitalized in 3 tertiary care neurology departments across 2 different racial populations (white and Asian). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20421579", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 1250, "text": "Early stroke risk is especially high in TIA patients with a high ABCD2 score of 4 or more (A age over 60 years [1 point]: B blood pressure > 140/90 mmHg [1 point]: C Clinical features, including unilateral weakness [2 points] and speech disturbance without weakness [1 point] D2: Diabetes [1 point] and Duration of symptoms [1 point for < 60 min and 2 points for > 60 min]), acute ischemic lesions on diffusion weighted image, > 50% carotid stenosis, severe intracranial artery stenosis, microembolic signals on transcranial Doppler, atrial fibrillation, or hypercoagulable states.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19803400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "STUDY OBJECTIVE: We evaluate, in admitted patients with transient ischemic attack, the accuracy of the ABCD(2) (age [A], blood pressure [B], clinical features [weakness/speech disturbance] [C], transient ischemic attack duration [D], and diabetes history [D]) score in predicting ischemic stroke within 7 days. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19556026", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 654, "text": "Our goal was to compare the very early predictive accuracy of the most relevant clinical scores [age, blood pressure, clinical features and duration of symptoms (ABCD) score, ABCD and diabetes (ABCD2) score, ABCD and brain infarction on imaging score, ABCD2 and brain infarction on imaging score, ABCD and prior TIA within 1 week of the index event (ABCD3) score, California Risk Score, Essen Stroke Risk Score and Stroke Prognosis Instrument II] in consecutive transient ischemic attack (TIA) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The risk of stroke after a transient ischaemic attack (TIA) can be predicted by scores incorporating age, blood pressure, clinical features, duration (ABCD-score), and diabetes (ABCD2-score).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "BACKGROUND AND PURPOSE: The risk of stroke after a transient ischaemic attack (TIA) can be predicted by scores incorporating age, blood pressure, clinical features, duration (ABCD-score), and diabetes (ABCD2-score).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554497", "endSection": "abstract" } ] }, { "body": "Is Tuberous Sclerosis a genetic disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20041940", "http://www.ncbi.nlm.nih.gov/pubmed/23622183", "http://www.ncbi.nlm.nih.gov/pubmed/19506736", "http://www.ncbi.nlm.nih.gov/pubmed/15456557", "http://www.ncbi.nlm.nih.gov/pubmed/9006662", "http://www.ncbi.nlm.nih.gov/pubmed/24226526", "http://www.ncbi.nlm.nih.gov/pubmed/16818174", "http://www.ncbi.nlm.nih.gov/pubmed/22021912", "http://www.ncbi.nlm.nih.gov/pubmed/24310804", "http://www.ncbi.nlm.nih.gov/pubmed/9770187", "http://www.ncbi.nlm.nih.gov/pubmed/18245941", "http://www.ncbi.nlm.nih.gov/pubmed/22068806", "http://www.ncbi.nlm.nih.gov/pubmed/23749404", "http://www.ncbi.nlm.nih.gov/pubmed/23966835", "http://www.ncbi.nlm.nih.gov/pubmed/20073603", "http://www.ncbi.nlm.nih.gov/pubmed/2600265", "http://www.ncbi.nlm.nih.gov/pubmed/22497684", "http://www.ncbi.nlm.nih.gov/pubmed/19744185", "http://www.ncbi.nlm.nih.gov/pubmed/21547713", "http://www.ncbi.nlm.nih.gov/pubmed/21907282", "http://www.ncbi.nlm.nih.gov/pubmed/20087180", "http://www.ncbi.nlm.nih.gov/pubmed/23359422", "http://www.ncbi.nlm.nih.gov/pubmed/12582162", "http://www.ncbi.nlm.nih.gov/pubmed/19624715", "http://www.ncbi.nlm.nih.gov/pubmed/24159711", "http://www.ncbi.nlm.nih.gov/pubmed/23661441", "http://www.ncbi.nlm.nih.gov/pubmed/22736301", "http://www.ncbi.nlm.nih.gov/pubmed/12364343", "http://www.ncbi.nlm.nih.gov/pubmed/19297407", "http://www.ncbi.nlm.nih.gov/pubmed/23438619", "http://www.ncbi.nlm.nih.gov/pubmed/15340059", "http://www.ncbi.nlm.nih.gov/pubmed/22544534", "http://www.ncbi.nlm.nih.gov/pubmed/18080139", "http://www.ncbi.nlm.nih.gov/pubmed/2706800", "http://www.ncbi.nlm.nih.gov/pubmed/1293183", "http://www.ncbi.nlm.nih.gov/pubmed/23035046", "http://www.ncbi.nlm.nih.gov/pubmed/12869586", "http://www.ncbi.nlm.nih.gov/pubmed/22025691", "http://www.ncbi.nlm.nih.gov/pubmed/16757313", "http://www.ncbi.nlm.nih.gov/pubmed/22125079", "http://www.ncbi.nlm.nih.gov/pubmed/11288117", "http://www.ncbi.nlm.nih.gov/pubmed/8129414", "http://www.ncbi.nlm.nih.gov/pubmed/21309039", "http://www.ncbi.nlm.nih.gov/pubmed/1479601", "http://www.ncbi.nlm.nih.gov/pubmed/21301339", "http://www.ncbi.nlm.nih.gov/pubmed/24092520", "http://www.ncbi.nlm.nih.gov/pubmed/8825048" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4098", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1155" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1155", "o": "http://www.dbpedia.org/resource/Tuberous_sclerosis" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1155", "o": "Tuberous_sclerosis" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4098", "o": "Tuberous sclerosis-1, 191100" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4099", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1155" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4099", "o": "Tuberous sclerosis-2, 191100" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/Q61037", "o": "http://purl.uniprot.org/citations/10584558" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10584558", "o": "http://purl.uniprot.org/medline/20051947" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10584558", "o": "Genet. Res." }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136313033370014", "o": "Tuberin" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q61037", "o": "http://linkedlifedata.com/resource/#_5136313033370015" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q61037", "o": "http://linkedlifedata.com/resource/#_5136313033370014" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136313033370015", "o": "Tuberous sclerosis 2 protein homolog" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10584558", "o": "http://purl.uniprot.org/pubmed/10584558" } ], "ideal_answer": [ "Tuberous sclerosis is a genetic disorder with an autosomal dominant pattern of inheritance, variable expressivity, and incomplete penetrance. Two thirds of TSC cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them. Current genetic tests have difficulty locating the mutation in approximately 20% of individuals diagnosed with the disease. So far it has been mapped to two genetic loci, TSC1 and TSC2.\nTSC1 encodes for the protein hamartin, is located on chromosome 9 q34 and was discovered in 1997. TSC2 encodes for the protein Tuberin, is located on chromosome 16 p13.3 and was discovered in 1993. TSC2 is contiguous with PKD1, the gene involved in one form of polycystic kidney disease (PKD). Gross deletions affecting both genes may account for the 2% of individuals with TSC who also develop PKD in childhood. TSC2 has been associated with a more severe form of TSC. However, the difference is subtle and cannot be used to identify the mutation clinically. Estimates of the proportion of TSC caused by TSC2 range from 55% to 80-90%.", "Yes, Tuberous Sclerosis is a genetic disease, caused by mutations in the TSC1 or TSC2 gene." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/TSC2_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://www.uniprot.org/uniprot/TSC1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030342", "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:630", "http://www.uniprot.org/uniprot/TSC1_SCHPO", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.uniprot.org/uniprot/TSC2_SCHPO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005823", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012598", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC1_MOUSE", "http://www.uniprot.org/uniprot/TSC2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:0050325" ], "type": "yesno", "id": "52b06a68f828ad283c000005", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 65, "text": "Tuberous sclerosis complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24310804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Tuberous sclerosis is a rare genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24092520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Tuberous sclerosis complex (TSC) is a multisystem genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23966835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Tuberous sclerosis complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359422", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 464, "text": "The disease is caused by mutational inactivation of the tumor suppressor gene tuberous sclerosis complex 1 (TSC1) or TSC2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23035046", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 428, "text": "mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Tuberous sclerosis (TSC) is an autosomal-dominant genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22497684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Tuberous sclerosis is a rare genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Tuberous Sclerosis Complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22125079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Tuberous sclerosis complex (TSC) is a multiorgan genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22025691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Tuberous sclerosis complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22021912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21907282", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 311, "text": "Tuberous sclerosis complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21301339", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 75, "text": "Tuberous sclerosis complex (TSC) is a multiorgan genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20087180", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 411, "text": "In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20073603", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 169, "text": "Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20041940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The tuberous sclerosis gene 2 product tuberin is an important regulator of the mammalian target of rapamycin (mTOR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19744185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Tuberous sclerosis complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19624715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21547713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Tuberous sclerosis is a genetic disease with autosomal dominant inheritance,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18245941", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 722, "text": "PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18080139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Tuberous sclerosis complex (TSC) is a multiorgan genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16818174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Tuberous sclerosis complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16757313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Tuberous sclerosis is a rare genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15456557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Tuberous sclerosis complex (TSC) is a genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15340059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12869586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Tuberous sclerosis complex (TSC) is a genetic disease caused by mutations in either TSC1 or TSC2 tumor suppressor genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12582162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Mutation in either the TSC1 or TSC2 tumor suppressor gene is responsible for the inherited genetic disease of tuberous sclerosis complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12364343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1 in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or the tuberin gene (TSC2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11288117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Tuberous sclerosis is a rare genetic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9770187", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 101, "text": "Tuberous sclerosis (TS) is a genetic disease with prominent cutaneous and brain involvement ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8129414", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 200, "text": "TSC was recognized to be a genetic disease with autosomal dominant inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1293183", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 829, "text": "On average TSC families are very small; in most cases there are fewer than two informative meioses. The size distribution of chromosome 9 linked families was similar to that of non-linked families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1479601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 507, "text": "The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21309039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Tuberous sclerosis is a dominant hereditary disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2600265", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 283, "text": "Many of these advances originated from studies of the genetic disease tuberous sclerosis complex (TSC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24226526", "endSection": "abstract" } ] }, { "body": "Does TRIM37 gene mutation causes Mulibrey nanism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21865362", "http://www.ncbi.nlm.nih.gov/pubmed/16514549", "http://www.ncbi.nlm.nih.gov/pubmed/14757854", "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "http://www.ncbi.nlm.nih.gov/pubmed/16310976", "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "http://www.ncbi.nlm.nih.gov/pubmed/17551331", "http://www.ncbi.nlm.nih.gov/pubmed/23385855", "http://www.ncbi.nlm.nih.gov/pubmed/19334051", "http://www.ncbi.nlm.nih.gov/pubmed/11938494" ], "ideal_answer": [ "Yes, Mulibrey nanism is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050436", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050336" ], "type": "yesno", "id": "56c1f03cef6e394741000054", "snippets": [ { "offsetInBeginSection": 93, "offsetInEndSection": 225, "text": "OBJECTIVE: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865362", "endSection": "abstract" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1714, "text": "In MUL, mutations in TRIM37 lead to disturbance of sexual maturation, and fertility is severely compromised. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865362", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 298, "text": "It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19334051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Gynecological tumors in Mulibrey nanism and role for RING finger protein TRIM37 in the pathogenesis of ovarian fibrothecomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "title" }, { "offsetInBeginSection": 602, "offsetInEndSection": 864, "text": "To investigate the possible involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "abstract" }, { "offsetInBeginSection": 1684, "offsetInEndSection": 1918, "text": " In conclusion, inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14757854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Mutations in the TRIM37 gene underlie mulibrey nanism (muscle-liver-brain-eye nanism), a rare monogenic developmental disorder characterized by severe growth failure, characteristic dysmorphic features, cardiopathy, failure of sexual maturation, and metabolic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16514549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11938494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Novel mutations in the TRIM37 gene in Mulibrey Nanism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 450, "text": "Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16310976", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11938494", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11938494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14757854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Novel mutations in the TRIM37 gene in Mulibrey Nanism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "endSection": "title" }, { "offsetInBeginSection": 246, "offsetInEndSection": 348, "text": "Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Refractory congestive heart failure following delayed pericardectomy in a 12-year-old child with Mulibrey nanism due to a novel mutation in TRIM37", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385855", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17551331", "endSection": "title" }, { "offsetInBeginSection": 94, "offsetInEndSection": 227, "text": "OBJECTIVE: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11938494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "UNLABELLED: Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14757854", "endSection": "abstract" }, { "offsetInBeginSection": 67, "offsetInEndSection": 286, "text": "Mutations in TRIM37 underlie mulibrey nanism, a rare autosomal recessively inherited disorder with severe growth failure of prenatal onset, constrictive pericardium, hepatomegaly and characteristic dysmorphic features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16310976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Mutations in the TRIM37 gene underlie mulibrey nanism (muscle-liver-brain-eye nanism), a rare monogenic developmental disorder characterized by severe growth failure, characteristic dysmorphic features, cardiopathy, failure of sexual maturation, and metabolic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16514549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17551331", "endSection": "title" }, { "offsetInBeginSection": 246, "offsetInEndSection": 349, "text": "Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": " Few monogenic mutations causing human male infertility have been identified to date. We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": " Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. The pathogenetic mechanisms of mulibrey nanism are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11938494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": " Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord-stromal origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14757854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Mulibrey nanism (MUL) is a monogenic disorder with prenatal-onset growth failure, typical clinical characteristics, cardiopathy and tendency for a metabolic syndrome. It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19334051", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 386, "text": " We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. Twenty-eight male MUL patients of the Finnish national cohort aged 8.7 to 50.0 yr (median age, 28.8) at the end of observation were followed for 10 yr beginning from 2000-2001.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12754710", "endSection": "title" }, { "offsetInBeginSection": 86, "offsetInEndSection": 208, "text": "We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21865362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19329943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11938494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Novel mutations in the TRIM37 gene in Mulibrey Nanism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 350, "text": "Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108285", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 298, "text": "It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19334051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385855", "endSection": "abstract" } ] }, { "body": "Have thyronamines effects on fat tissue?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20880963" ], "ideal_answer": [ "thyronamines cause reduction of fat mass" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000273", "http://www.biosemantics.org/jochem#4251308" ], "type": "yesno", "id": "534bf050aeec6fbd07000015", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 947, "text": "Intraperitoneal or central injection of 3-T(1)AM or T(0)AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20880963", "endSection": "abstract" } ] }, { "body": "What is the genetic basis of progeria", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18796515", "http://www.ncbi.nlm.nih.gov/pubmed/16258283", "http://www.ncbi.nlm.nih.gov/pubmed/19842191", "http://www.ncbi.nlm.nih.gov/pubmed/12714972", "http://www.ncbi.nlm.nih.gov/pubmed/21217880", "http://www.ncbi.nlm.nih.gov/pubmed/19875478" ], "ideal_answer": [ "Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome in around 90% of patients" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011371", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.disease-ontology.org/api/metadata/DOID:630", "http://www.disease-ontology.org/api/metadata/DOID:0050325", "http://www.disease-ontology.org/api/metadata/DOID:3911" ], "type": "summary", "id": "52f7c91f2059c6d71c00002e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 240, "text": "Mandibuloacral dysplasia (MAD) is a rare autosomal recessive progeroid syndrome due to mutations in genes encoding nuclear lamina proteins, lamins A/C (LMNA) or prelamin A processing enzyme, and zinc metalloproteinase (ZMPSTE24)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18796515", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 617, "text": "genetic defects in the nuclear envelope protein prelamin A or in the FACE-1 metalloprotease (also called Zmspte24) involved in prelamin A proteolytic maturation, cause the accumulation of an abnormal form of this protein and the subsequent disruption of nuclear envelope integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258283", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 224, "text": "we present evidence of mutations in lamin A (LMNA) as the cause of this disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12714972", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 496, "text": "The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21217880", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 222, "text": "Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia are well-recognized allelic autosomal dominant and recessive progeroid disorders, respectively, due to mutations in lamin A/C (LMNA) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19875478", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 496, "text": "The underlying defect is usually a homozygous mutation of LMNA, or a combined defect of LMNA and another gene, for example, ZMPSTE-24", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19842191", "endSection": "abstract" } ] }, { "body": "What type of DNA repair pathways is initiated by AlkA glycosylase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10455196", "http://www.ncbi.nlm.nih.gov/pubmed/10455195", "http://www.ncbi.nlm.nih.gov/pubmed/12832627", "http://www.ncbi.nlm.nih.gov/pubmed/11266119", "http://www.ncbi.nlm.nih.gov/pubmed/8805338", "http://www.ncbi.nlm.nih.gov/pubmed/10675345", "http://www.ncbi.nlm.nih.gov/pubmed/21491902", "http://www.ncbi.nlm.nih.gov/pubmed/9637245", "http://www.ncbi.nlm.nih.gov/pubmed/18270439", "http://www.ncbi.nlm.nih.gov/pubmed/9430628", "http://www.ncbi.nlm.nih.gov/pubmed/10946229", "http://www.ncbi.nlm.nih.gov/pubmed/12853604", "http://www.ncbi.nlm.nih.gov/pubmed/10375529", "http://www.ncbi.nlm.nih.gov/pubmed/9535832", "http://www.ncbi.nlm.nih.gov/pubmed/9895121", "http://www.ncbi.nlm.nih.gov/pubmed/10363024", "http://www.ncbi.nlm.nih.gov/pubmed/12379112", "http://www.ncbi.nlm.nih.gov/pubmed/22683793", "http://www.ncbi.nlm.nih.gov/pubmed/24810496" ], "ideal_answer": [ "The AlkA protein (3-methyladenine DNA glycosylase II protein) is a monofunctional DNA glycosylase that recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair (BER) pathway." ], "exact_answer": [ "base excision repair (BER) pathway" ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016798", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003905", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045647", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006281", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0019104" ], "type": "factoid", "id": "55421398ccca0ce74b000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "The Escherichia coli 3-methyladenine DNA glycosylase II protein (AlkA) recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21491902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Schizosaccharomyces pombe has two paralogues of 3-methyladenine DNA glycosylase, Mag1p and Mag2p, which share homology with Escherichia coli AlkA. To clarify the function of these redundant enzymes in base excision repair (BER) of alkylation damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18270439", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 872, "text": "Escherichia coli alkA tagA double mutants, which are deficient in the repair of alkylated bases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10375529", "endSection": "abstract" }, { "offsetInBeginSection": 1813, "offsetInEndSection": 2168, "text": "AlkA, a monofunctional DNA glycosylase that acts on alkylated bases, is structurally homologous to endo III. We have now identified a shared active site motif amongst these three proteins. Using this motif as a protein database searching tool, we find that it is present in a number of other base-excision DNA repair proteins that process diverse lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8805338", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 269, "text": "Alkylation damage is removed by the action of DNA glycosylases, which initiate the base excision repair pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10375529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Enzymatic repair of 5-formyluracil. I. Excision of 5-formyluracil site-specifically incorporated into oligonucleotide substrates by alka protein (Escherichia coli 3-methyladenine DNA glycosylase II).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10455195", "endSection": "title" }, { "offsetInBeginSection": 1512, "offsetInEndSection": 1731, "text": "These results suggest that fU present in DNA can be restored by two independent repair pathways, i.e. the base excision repair pathway initiated by AlkA and the methyl-directed mismatch repair pathway initiated by MutS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10455196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "3-Methyladenine DNA glycosylase II (AlkA) is a DNA-repair enzyme that removes alkylated bases in DNA via the base-excision repair (BER) pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683793", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 220, "text": "Mismatch formation between 5-formyluracil and guanine during dna replication and its recognition by two proteins involved in base excision repair (AlkA) and mismatch repair (MutS).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10455196", "endSection": "title" }, { "offsetInBeginSection": 1516, "offsetInEndSection": 1735, "text": "These results suggest that fU present in DNA can be restored by two independent repair pathways, i.e. the base excision repair pathway initiated by AlkA and the methyl-directed mismatch repair pathway initiated by MutS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10455196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Base excision repair is initiated by DNA glycosylases removing inappropriate bases from DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9430628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The Escherichia coli AlkA protein is a base excision repair glycosylase that removes a variety of alkylated bases from DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10675345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Human alkyladenine glycosylase (AAG) and Escherichia coli 3-methyladenine glycosylase (AlkA) are base excision repair glycosylases that recognize and excise a variety of alkylated bases from DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10946229", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1734, "text": "the base excision repair pathway initiated by AlkA and the methyl-directed mismatch repair pathway initiated by MutS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10455196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The Escherichia coli 3-methyladenine DNA glycosylase II protein (AlkA) recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21491902", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 326, "text": "Alkylation damage is removed by the action of DNA glycosylases, which initiate the base excision repair pathway and protect the sequence information of the genome [3-5]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10375529", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 376, "text": "The alkylbase DNA glycosylase, AlkA, initiates repair by removal of the damaged base, whereas endonuclease V, Endo V, hydrolyses the second phosphodiester bond 3' to the lesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12853604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Base excision repair is initiated by DNA glycosylases removing inappropriate bases from DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9430628", "endSection": "abstract" } ] }, { "body": "Is there any protein that undergoes both mono-ubiquitination and poly-ubiquitination?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19176477", "http://www.ncbi.nlm.nih.gov/pubmed/20423330", "http://www.ncbi.nlm.nih.gov/pubmed/22045334", "http://www.ncbi.nlm.nih.gov/pubmed/16154111", "http://www.ncbi.nlm.nih.gov/pubmed/20351748", "http://www.ncbi.nlm.nih.gov/pubmed/12794086", "http://www.ncbi.nlm.nih.gov/pubmed/17121848", "http://www.ncbi.nlm.nih.gov/pubmed/24141722", "http://www.ncbi.nlm.nih.gov/pubmed/18248624", "http://www.ncbi.nlm.nih.gov/pubmed/20006583", "http://www.ncbi.nlm.nih.gov/pubmed/22113972", "http://www.ncbi.nlm.nih.gov/pubmed/20453833", "http://www.ncbi.nlm.nih.gov/pubmed/12127959", "http://www.ncbi.nlm.nih.gov/pubmed/11156945", "http://www.ncbi.nlm.nih.gov/pubmed/20538595", "http://www.ncbi.nlm.nih.gov/pubmed/17963781" ], "triples": [ { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/D7LBU2", "o": "http://linkedlifedata.com/resource/#_44374C42553200A" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_44374C42553200A", "o": "Histone mono-ubiquitination 1" } ], "ideal_answer": [ "Yes, there are some rare cases where a protein can be both mono-ubiquitinated and poly-ubiquitinated." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054875", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031396", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031398", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016567", "http://www.uniprot.org/uniprot/UBIQ_AVESA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057149", "http://www.uniprot.org/uniprot/UBIQP_PHYIN" ], "type": "yesno", "id": "530c7cfd970c65fa6b00000c", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 292, "text": "The yeast G protein alpha subunit Gpa1 represents a rare example of a protein that undergoes both mono- and poly-ubiquitination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19176477", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 748, "text": "Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141722", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 400, "text": "These fingers possess E3 activities of mono-ubiquitination and poly-ubiquitination, respectively, with ubiquitin-conjugating enzyme (E2)-binding capabilities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22113972", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 827, "text": "Instead of promoting poly-ubiquitination and degradation, we show that Smurf2 actually induces multiple mono-ubiquitination of Smad3 in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22045334", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 738, "text": "mono-ubiquitination of CIITA dramatically increases its transactivity whereas poly-ubiquitination leads to CIITA degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538595", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1008, "text": "This leads to a model in which Lys134 of LDB1 can be either mono-ubiquitinated, leading to stabilization, or poly-ubiquitinated, leading to degradation by the proteasome pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20423330", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 539, "text": " mono-ubiquitination of CIITA increases its transactivity, whereas poly-ubiquitination of CIITA leads to its degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20351748", "endSection": "abstract" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1006, "text": "PS1 ubiquitination after PI3K inhibition is represented by the multiple mono-ubiquitination, instead of poly-ubiquitination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20006583", "endSection": "abstract" }, { "offsetInBeginSection": 1270, "offsetInEndSection": 1608, "text": "Our observations support a novel functional relationship between parkin and Hsc/Hsp70 and support the notion that parkin is a multi-purpose E3 ubiquitin ligase capable of modifying proteins either via attachment of alternatively linked poly-ubiquitin chains or through multiple mono-ubiquitination to achieve alternate biological outcomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18248624", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1065, "text": "our results indicate that Hsp70 facilitates CHIP-mediated poly-ubiquitination of Smad1 whereas it attenuates CHIP-meditated mono-ubiquitination of Smad1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17963781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Whereas poly-ubiquitination targets protein substrates for proteasomal degradation, mono-ubiquitination is known to regulate protein trafficking in the endosomal system and to target cargo proteins for lysosomal degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17121848", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1615, "text": "Our results suggest that oxidative stress induces not only poly-ubiquitination but also mono-ubiquitination of LDH-A, which may be involved in its lysosomal degradation during unloading.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16154111", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 910, "text": "wild type Smad4 is a relatively stable protein that undergoes mono- or oligo-ubiquitination, a modification not linked to protein degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12794086", "endSection": "abstract" }, { "offsetInBeginSection": 1626, "offsetInEndSection": 1813, "text": "These data suggest that oligo-ubiquitination positively regulates Smad4 function, whereas poly-ubiquitination primarily occurs in unstable cancer mutants and leads to protein degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12794086", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 676, "text": "We found that Ro52 was strongly conjugated by a single molecule of ubiquitin in cells. Although the biological relevance of this mono-ubiquitination was not defined, the function of Ro52 might be modified by the mono-ubiquitination. We also found that Ro52 was conjugated with poly-ubiquitin chain in cells (poly-ubiquitination)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12127959", "endSection": "abstract" } ] }, { "body": "Which are the musculoskeletal manifestations of Marfan syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21971724", "http://www.ncbi.nlm.nih.gov/pubmed/17620463", "http://www.ncbi.nlm.nih.gov/pubmed/6481730", "http://www.ncbi.nlm.nih.gov/pubmed/20686061", "http://www.ncbi.nlm.nih.gov/pubmed/19726741" ], "ideal_answer": [ "Musculoskeletal manifestations of Marfan syndrome include scoliosis, dural ectasia, pectus excavatum and carinatum, arachnodactyly, otto pelvis (protrusio acetabuli), dolichostenomelia and ligamentous laxity." ], "exact_answer": [ [ "scoliosis" ], [ "dural ectasia" ], [ "pectus excavatum and carinatum" ], [ "arachnodactyly" ], [ "otto pelvis", "protrusio acetabuli" ], [ "dolichostenomelia" ], [ "ligamentous laxity" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009141" ], "type": "list", "id": "532f0b2cd6d3ac6a3400002c", "snippets": [ { "offsetInBeginSection": 220, "offsetInEndSection": 329, "text": "Musculoskeletal manifestations include scoliosis, dural ectasia, protrusio acetabuli, and ligamentous laxity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19726741", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 587, "text": "Scoliosis, pectus excavatum and carinatum, arachnodactyly, and acetabular protrusion are common musculoskeletal manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17620463", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 308, "text": "Two cases are described in which protrusio acetabuli was a major problem. Otto pelvis should be considered as one of the musculoskeletal manifestations of Marfan's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6481730", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1594, "text": "The following musculoskeletal abnormalities were found: pectus in 3 patients (11%), pectus and scoliosis in 19 (73%), dolichostenomelia in 11 (42%) and arachnodactyly in 21 (80%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21971724", "endSection": "abstract" }, { "offsetInBeginSection": 1815, "offsetInEndSection": 2179, "text": "Musculoskeletal clinicians should be aware of the diagnostic features of Marfan syndrome. Patients with three to four physically evident features, or two highly specific features (e.g., thumb and wrist signs, craniofacial features, dural ectasia, or protrusio), should be carefully reexamined and possibly referred for an echocardiogram or a genetics consultation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20686061", "endSection": "abstract" } ] }, { "body": "What is the \"Proteomic ruler\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25225357" ], "ideal_answer": [ "The MS signal of histones can be used as a \"proteomic ruler\" because it is proportional to the amount of DNA in the sample, which in turn depends on the number of cells. As a result, our proteomic ruler approach adds an absolute scale to the MS readout and allows estimation of the copy numbers of individual proteins per cell." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543" ], "type": "summary", "id": "54d7b457e19bba8909000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "A \"proteomic ruler\" for protein copy number and concentration estimation without spike-in standards.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25225357", "endSection": "title" }, { "offsetInBeginSection": 451, "offsetInEndSection": 791, "text": "We show that the MS signal of histones can be used as a \"proteomic ruler\" because it is proportional to the amount of DNA in the sample, which in turn depends on the number of cells. As a result, our proteomic ruler approach adds an absolute scale to the MS readout and allows estimation of the copy numbers of individual proteins per cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25225357", "endSection": "abstract" } ] }, { "body": "What is the mechanism by which HIV-1-encoded Vif protein allows virus replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21725586", "http://www.ncbi.nlm.nih.gov/pubmed/23689841", "http://www.ncbi.nlm.nih.gov/pubmed/23707381", "http://www.ncbi.nlm.nih.gov/pubmed/23316055", "http://www.ncbi.nlm.nih.gov/pubmed/24189052", "http://www.ncbi.nlm.nih.gov/pubmed/22728817", "http://www.ncbi.nlm.nih.gov/pubmed/19887642", "http://www.ncbi.nlm.nih.gov/pubmed/20147392" ], "ideal_answer": [ "The HIV-1 Vif protein counteracts the antiviral activity of the APOBEC3 family by targeting the proteins for degradation through the ubiquitin-proteasome pathway. More specifically, Vif, serving as a substrate receptor, facilitates ubiquitination of APOBEC3 proteins by forming a Cullin5-based E3 ubiquitin ligase complex, which targets APOBEC3 proteins for rapid proteasomal degradation." ], "type": "summary", "id": "54dfce9b1388e8454a00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707381", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "The human immunodeficiency virus type 1 (HIV-1) Vif protein counteracts the antiviral activity of the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of proteins by targeting the proteins for degradation through the ubiquitin-proteasome pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707381", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 199, "text": "The host protein APOBEC3G (A3G) can limit HIV-1 replication. Its protective effect is overcome by the HIV-1 'viral infectivity factor' (Vif), which targets A3G for proteosomal degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23689841", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 589, "text": " Vif is thought to primarily overcome APOBEC3G through an interaction that mediates APOBEC3G ubiquitination and results in its proteasomal degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316055", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 694, "text": "However, Vif may also inhibit APOBEC3G mRNA translation, virion encapsidation, and deamination activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316055", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 470, "text": "Vif counteracts the packaging of two cellular cytidine deaminases named APOBEC3G (A3G) and A3F by diverse mechanisms including the recruitment of an E3 ubiquitin ligase complex and the proteasomal degradation of A3G/A3F, the inhibition of A3G mRNA translation or by a direct competition mechanism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728817", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 757, "text": "In addition, Vif appears to be an active partner of the late steps of viral replication by participating in virus assembly and Gag processing, thus regulating the final stage of virion formation notably genomic RNA dimerization and by inhibiting the initiation of reverse transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22728817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Human apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) 3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory function of Vif is related to its ability to degrade A3G in the proteasome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21725586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Polyubiquitination of APOBEC3G is essential for its degradation by HIV-1 Vif", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20147392", "endSection": "title" }, { "offsetInBeginSection": 684, "offsetInEndSection": 798, "text": "These data suggest that polyubiquitination of APOBEC3G, not that of HIV-1 Vif, is crucial for APOBEC3G degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20147392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "During coevolution with the host, HIV-1 developed the ability to hijack the cellular ubiquitin/proteasome degradation pathway to counteract the antiviral activity of APOBEC3G (A3G), a host cytidine deaminase that can block HIV-1 replication. Abrogation of A3G function involves the HIV-1 Vif protein, which binds A3G and serves as an adapter molecule to recruit A3G to a Cullin5-based E3 ubiquitin ligase complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887642", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 632, "text": "HIV-1 counteracts APOBEC3 proteins by encoding the viral protein Vif, which contains distinct domains that specifically interact with these APOBEC3 proteins to ensure their proteasomal degradation, allowing virus replication to proceed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24189052", "endSection": "abstract" } ] }, { "body": "Which proteins are the different isoforms of the p38 MAP kinase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24107108", "http://www.ncbi.nlm.nih.gov/pubmed/22720195", "http://www.ncbi.nlm.nih.gov/pubmed/19622861", "http://www.ncbi.nlm.nih.gov/pubmed/18256287", "http://www.ncbi.nlm.nih.gov/pubmed/18641461", "http://www.ncbi.nlm.nih.gov/pubmed/14522818", "http://www.ncbi.nlm.nih.gov/pubmed/22175015", "http://www.ncbi.nlm.nih.gov/pubmed/16022178", "http://www.ncbi.nlm.nih.gov/pubmed/9430721", "http://www.ncbi.nlm.nih.gov/pubmed/19251701", "http://www.ncbi.nlm.nih.gov/pubmed/23722928", "http://www.ncbi.nlm.nih.gov/pubmed/23878395", "http://www.ncbi.nlm.nih.gov/pubmed/17088247", "http://www.ncbi.nlm.nih.gov/pubmed/17591882", "http://www.ncbi.nlm.nih.gov/pubmed/17855341", "http://www.ncbi.nlm.nih.gov/pubmed/17241234" ], "ideal_answer": [ "The p38 Mitogen-Activated Protein (MAP) kinase, a serine/threonine kinase, is one of the best characterized kinases in the inflammatory process. There are four isoforms of the enzyme (p38alpha, p38beta, p38gamma and p38delta), which differ in tissue distribution, regulation of kinase activation and subsequent phosphorylation of downstream substrates. Among the four identified p38 isoforms (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), the \u03b1-form is the most fully studied.", "The mammalian p38 mitogen-activated protein kinases (MAPKs) family is composed of four members (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), which are very similar in amino acid sequence but differ in their expression patterns.", "The mitogen-activated protein kinase (MAPK) p38 is a Ser/Thr kinase, originally isolated from lipopolysaccharide-stimulated monocytes. There are four isoforms of the enzyme (p38alpha, p38beta, p38gamma and p38delta), which differ in tissue distribution, regulation of kinase activation and subsequent phosphorylation of downstream substrates. The p38 Mitogen-Activated Protein (MAP) kinase, a serine/threonine kinase, is one of the best characterized kinases in the inflammatory process. Among the four identified p38 isoforms (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), the \u03b1-form is the most fully studied and plays a central role in the biosynthesis of the proinflammatory cytokines i.e. IL-1\u03b2 and TNF-\u03b1 at the translational and transcriptional levels. " ], "exact_answer": [ [ "p38alpha", "p38\u03b1" ], [ "p38beta", "p38\u03b2" ], [ "p38gamma", "p38\u03b3" ], [ "p38delta", "p38\u03b4" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020033", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048051", "http://www.uniprot.org/uniprot/NCAP_BDVV", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004707", "http://www.uniprot.org/uniprot/CAPSD_CARMS" ], "type": "list", "id": "5512c1ee6a8cde6b72000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "The p38 Mitogen-Activated Protein (MAP) kinase, a serine/threonine kinase, is one of the best characterized kinases in the inflammatory process. Among the four identified p38 isoforms (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), the \u03b1-form is the most fully studied and plays a central role in the biosynthesis of the proinflammatory cytokines i.e. IL-1\u03b2 and TNF-\u03b1 at the translational and transcriptional levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107108", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 692, "text": "The p38 mitogen-activated protein kinase (MAPK) is one of the kinase pathways that regulate the production of IL-1\u03b2 and TNF\u03b1. Importantly, small molecule inhibitors of the p38 MAPK family have been developed and show efficacy in blocking the production of IL-1\u03b2 and TNF\u03b1. The p38 family consists of at least four isoforms (p38\u03b1, \u03b2, \u03b3, \u03b4) encoded by separate genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22720195", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 257, "text": "Defining the roles of the various p38 family members, specifically p38alpha and p38beta, in these processes has been difficult.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17855341", "endSection": "abstract" }, { "offsetInBeginSection": 1841, "offsetInEndSection": 2070, "text": " The anomalous p38 inhibitor effect on IL-1alpha induction of MMP-3 and phosphorylation of p38 delta/gamma suggests complex interactions between p38 MAP kinase isoforms and their differential uses by TNFalpha and IL-1alpha in TM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591882", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1497, "text": "Human and porcine TM cells expressed p38 alpha, beta, delta, and gamma isoforms, which migrate coincident with bands of specific phosphorylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17591882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "The mitogen-activated protein kinase (MAPK) p38 is a Ser/Thr kinase, originally isolated from lipopolysaccharide-stimulated monocytes. There are four isoforms of the enzyme (p38alpha, p38beta, p38gamma and p38delta), which differ in tissue distribution, regulation of kinase activation and subsequent phosphorylation of downstream substrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16022178", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 266, "text": "We report the molecular cloning of a novel isoform of p38 MAP kinase, p38 beta 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9430721", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 557, "text": "The p38 MAP kinase kinase MKK6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma MAP kinase isoforms, while MKK3 activates only p38 alpha and p38 gamma MAP kinase isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9430721", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 214, "text": " four identified p38 isoforms (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The mammalian p38 mitogen-activated protein kinases (MAPKs) family is composed of four members (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), which are very similar in amino acid sequence but differ in their expression patterns. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22175015", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 772, "text": "Four p38 isoforms (p38alpha, p38beta, p38gamma and p38delta) exist in mammalian cells, being p38alpha and p38gamma the most abundantly expressed isoforms in adult skeletal muscle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18641461", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 334, "text": "Among the four identified p38 isoforms (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), the \u03b1-form is the most fully studied and plays a central role in the biosynthesis of the proinflammatory cytokines i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "The p38 mitogen-activated protein kinases are activated in response to various extracellular signals in eukaryotic cells and play a critical role in the cellular responses to these signals. The four mammalian isoforms (p38alpha, p38beta, p38gamma, and p38delta) are coexpressed and coactivated in the same cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241234", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 293, "text": "four p38 isoforms ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23878395", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 516, "text": "p38 MAPK isoforms are becoming increasingly important for a variety of cellular functions. The physiological functions of p38\u03b1 and -\u03b2 are now well documented in contrast to -\u03b3 and -\u03b4 which are comparatively under-studied and ill-defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23722928", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 340, "text": "Of the four p38 isoforms known to date, two (p38alpha and p38beta) have been identified as targets for cytokine-suppressive anti-inflammatory drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622861", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 646, "text": " the contribution of each of the four p38 isoforms (encoded by different genes) to senescence induction is unclear. In the current study, we demonstrated that p38alpha and p38gamma, but not p38beta, play an essential role in oncogenic ras-induced senescence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19251701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Involvement of the p38 mitogen-activated protein kinase alpha, beta, and gamma isoforms in myogenic differentiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256287", "endSection": "title" }, { "offsetInBeginSection": 267, "offsetInEndSection": 384, "text": "we showed here that p38alpha, beta, and gamma are expressed with distinct expression patterns during differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18256287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The p38 family of kinases is a subgroup of the mitogen-activated protein kinase family. It is composed of four isoforms and is involved in critical biological processes as well as in inflammatory diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17088247", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 317, "text": "p38alpha and -beta2 are ubiquitously expressed, whereas p38gamma and -delta appear to have more restricted expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14522818", "endSection": "abstract" } ] }, { "body": "Are pseudogenes enriched with housekeeping protein families?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18957444" ], "ideal_answer": [ "Yes, housekeeping families tend to be enriched with a large number of pseudogenes." ], "exact_answer": "yes", "type": "yesno", "id": "5709f212cf1c325851000020", "snippets": [ { "offsetInBeginSection": 1370, "offsetInEndSection": 1446, "text": "housekeeping families tend to be enriched with a large number of pseudogenes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18957444", "endSection": "abstract" } ] }, { "body": "What is the mechanism of cementogenesis in pulp regeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18636796", "http://www.ncbi.nlm.nih.gov/pubmed/21512722", "http://www.ncbi.nlm.nih.gov/pubmed/23146645", "http://www.ncbi.nlm.nih.gov/pubmed/21854758" ], "ideal_answer": [ "The dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone. Dental follicle cells attach to Hertwig's epithelial root sheath (HERS), and pulp cells in the cementum promoting cementogenesis. The temporospatial regulation of Wnt/\u00df-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts.", "Our results indicate that persistent stabilization of \u00df-catenin in the dental mesenchyme leads to premature differentiation of odontoblasts and differentiation of cementoblasts, and induces excessive dentin and cementum formation in vivo. It is known that the dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone. Wnt/\u00df-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. New vital tissues can be regenerated in permanent canine teeth after pulpectomy and enlargement of the apical foramen. Constitutive stabilization of \u00df-catenin in the dental mesenchyme leads to excessive dentin and cementum formation. These results suggest that temporospatial regulation of Wnt/\u00df-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts, and that inhibition of Wnt/\u00df-catenin signaling may be important for the formation of dentin and cementum during tooth development. HERS cells played a role in the induction and maturation of cementum-like tissues formed by DF cells. Essential roles of Wnt/\u00df-catenin signaling in tooth morphogenesis have been well known. " ], "type": "summary", "id": "553ba7b7f321868558000006", "snippets": [ { "offsetInBeginSection": 1427, "offsetInEndSection": 1544, "text": "New vital tissues can be regenerated in permanent canine teeth after pulpectomy and enlargement of the apical foramen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146645", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 219, "text": "The loss of dental pulp may weaken teeth, rendering them susceptible to reinfection, fracture, and subsequent tooth loss. Therefore, regeneration of pulp is considered an ideal treatment to preserve teeth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Constitutive stabilization of \u00df-catenin in the dental mesenchyme leads to excessive dentin and cementum formation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21854758", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Wnt/\u00df-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. Essential roles of Wnt/\u00df-catenin signaling in tooth morphogenesis have been well known", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21854758", "endSection": "abstract" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 2013, "text": "Our results indicate that persistent stabilization of \u00df-catenin in the dental mesenchyme leads to premature differentiation of odontoblasts and differentiation of cementoblasts, and induces excessive dentin and cementum formation in vivo. These results suggest that temporospatial regulation of Wnt/\u00df-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts, and that inhibition of Wnt/\u00df-catenin signaling may be important for the formation of dentin and cementum during tooth development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21854758", "endSection": "abstract" }, { "offsetInBeginSection": 2015, "offsetInEndSection": 2139, "text": "Local modulation of Wnt/\u00df-catenin signaling has therapeutic potential to improve the regeneration of dentin and periodontium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21854758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "It is known that the dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512722", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 444, "text": " but little information is available about the regulation of DF cell differentiation into either cementogenic or osteogenic cell lineages for the regeneration of diseased periodontal tissue. Here, we investigated the roles of DF, Hertwig's epithelial root sheath (HERS), and pulp cells in the cementum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512722", "endSection": "abstract" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1677, "text": "These results suggest that the combined use of DF, HERS, and pulp cells could direct DF cell differentiation into cementoblasts and/or osteoblasts in vivo, thus providing a novel strategy for the successful repair and regeneration of diseased periodontal tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512722", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 955, "text": " HERS cells played a role in the induction and maturation of cementum-like tissues formed by DF cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512722", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1062, "text": " implants of DF cells in the presence of pulp cells led to the formation of bone-like tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512722", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1414, "text": "Interestingly, in the presence of both HERS and pulp cells, DF cells formed both cementum-like and bone-like tissues. We demonstrated that while HERS cells are able to induce DF cell differentiation into cementoblasts and promote cementum formation, pulp cells could direct DF cell differentiation into osteoblasts and enhance alveolar bone formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21512722", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 298, "text": "Periodontal ligament (PDL) and cementum complex and dentin pulp complex have been tissue engineered using human dental pulp stem cells and PDL stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18636796", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1048, "text": "Histological, immunohistochemical, and scanning electronic microscopy examinations results showed that bioengineered dentin could induce cementogenesis and PDL formation, and condense PDL arranged perpendicularly on the dentin surface via a layer of cementum-like tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18636796", "endSection": "abstract" } ] }, { "body": "What are the reported adverse effects of gabapentin used in children?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10030434", "http://www.ncbi.nlm.nih.gov/pubmed/11274308", "http://www.ncbi.nlm.nih.gov/pubmed/16490100", "http://www.ncbi.nlm.nih.gov/pubmed/8603631", "http://www.ncbi.nlm.nih.gov/pubmed/15072101", "http://www.ncbi.nlm.nih.gov/pubmed/12199723", "http://www.ncbi.nlm.nih.gov/pubmed/8617181", "http://www.ncbi.nlm.nih.gov/pubmed/9120226", "http://www.ncbi.nlm.nih.gov/pubmed/8648543", "http://www.ncbi.nlm.nih.gov/pubmed/7489697", "http://www.ncbi.nlm.nih.gov/pubmed/11305405", "http://www.ncbi.nlm.nih.gov/pubmed/12022084", "http://www.ncbi.nlm.nih.gov/pubmed/22134010", "http://www.ncbi.nlm.nih.gov/pubmed/11361047", "http://www.ncbi.nlm.nih.gov/pubmed/19193587", "http://www.ncbi.nlm.nih.gov/pubmed/23112238" ], "ideal_answer": [ "Limited literature data, suggest that gabapentin may cause rash that is severe enough to necessitate discontinuation in a small percentage of children.\nIn a large survey of all age groups: The commonest adverse effects seen were somnolence, fainting, ataxia, nystagmus, tremor and headache, fatigue. However, their incidence was low and intensity mild. In a pediatric group only somnolence and dizziness were reported in 2 out of 33 patients.\nBehavioural adverse effects are more common in children with intellectual disability and attention deficit, worse in <10yo : hyperactivity, defiance, irritability, agitation, aggression, explosive outbursts, oppositional behavior, often warranting discontinuation of the medication." ], "exact_answer": [ [ "Skin reactions" ], [ "Somnolence", "drowsiness", "sedation", "lassitude" ], [ "Dizziness" ], [ "hyperactivity" ], [ "defiance" ], [ "irritability" ], [ "agitation" ], [ "aggression" ], [ "explosive outbursts" ], [ "oppositional behavior" ], [ "malaise" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004362", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002648", "http://www.biosemantics.org/jochem#4258191" ], "type": "list", "id": "515db70c298dcd4e51000017", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 288, "text": "he purpose of our study was to review our experience with using gabapentin to treat insomnia in children. We identified 23 children,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23112238", "endSection": "sections.0" }, { "offsetInBeginSection": 839, "offsetInEndSection": 880, "text": "Adverse effects were noted in 6 children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23112238", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 129, "text": "To determine the effectiveness of gabapentin as an add-on therapy in children presenting with overactive bladder (OAB)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134010", "endSection": "sections.0" }, { "offsetInBeginSection": 651, "offsetInEndSection": 741, "text": "Data were analyzed in 30 patients as treatment was terminated in 1 due to adverse effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134010", "endSection": "sections.0" }, { "offsetInBeginSection": 1307, "offsetInEndSection": 1473, "text": "Gabapentin gives moderate results in children with OAB refractory to conventional anticholinergics. In general, the drug is well tolerated with fewer adverse effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134010", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 159, "text": "To describe a child who developed a skin reaction during gabapentin therapy and discuss how we evaluated the probability of an adverse drug reaction", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19193587", "endSection": "sections.0" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1093, "text": "In contrast to other antiepileptic drugs, skin reactions to gabapentin are considered uncommon. In adults, reported prevalence of rash possibly related to gabapentin range from 1% to 10%. A postmarketing surveillance study reported gabapentin treatment failure as a consequence of rash in 0.4% of 3000 patients. The product monograph does not mention rash in children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19193587", "endSection": "sections.0" }, { "offsetInBeginSection": 1227, "offsetInEndSection": 1514, "text": "This case, and limited literature data, suggest that gabapentin may cause rash that is severe enough to necessitate discontinuation in a small percentage of children. Further research is needed to determine the actual incidence and severity of gabapentin-related rash in this population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19193587", "endSection": "sections.0" }, { "offsetInBeginSection": 285, "offsetInEndSection": 425, "text": "Five patients treated in the Children's Hospital Pain Control Service for intractable neuropathic pain were included in gabapentin treatment", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16490100", "endSection": "sections.0" }, { "offsetInBeginSection": 614, "offsetInEndSection": 738, "text": "We noticed a rapid improvement, in 1 week, of our patients' VAS scores (from 9 or 10 to 4 or 3) with minimal adverse effects", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16490100", "endSection": "sections.0" }, { "offsetInBeginSection": 206, "offsetInEndSection": 277, "text": "The charts of all children given gabapentin for seizures were reviewed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15072101", "endSection": "sections.0" }, { "offsetInBeginSection": 906, "offsetInEndSection": 990, "text": "Only 8 children (7%) reported adverse effects, and the drug was discontinued in two.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15072101", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A postmarketing surveillance study of gabapentin as add-on therapy for 3,100 patients in England.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12199723", "endSection": "title" }, { "offsetInBeginSection": 880, "offsetInEndSection": 948, "text": "The cohort comprised 3,100 patients, of whom 136 (4%) were children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12199723", "endSection": "sections.0" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1252, "text": "The most frequently reported adverse events reported during the first month of treatment, drowsiness/sedation, dizziness, and malaise/lassitude, also were the commonest reasons for discontinuing GBP and reported as suspected adverse drug reactions (ADRs)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12199723", "endSection": "sections.0" }, { "offsetInBeginSection": 1495, "offsetInEndSection": 1667, "text": "Neurologic-related events were the most frequently reported adverse events. They also were the commonest reasons for discontinuing treatment and reported as suspected ADRs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12199723", "endSection": "sections.0" }, { "offsetInBeginSection": 144, "offsetInEndSection": 391, "text": "We reviewed the reports in the literature on the safety, adverse effects and tolerance of GBP as treatment, used as monotherapy or associated with other drugs, in epilepsies in patients of all age groups, including children, adults and the elderly", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12022084", "endSection": "sections.0" }, { "offsetInBeginSection": 437, "offsetInEndSection": 815, "text": "GBP is a well tolerated drug when used for monotherapy or associated with other antiepileptic drugs. The commonest adverse effects seen were somnolence, fainting, ataxia, nystagmus, tremor and headache. However, their incidence was low and intensity mild. There was no clear relationship between the dose given and appearance of side effects, except for fainting and somnolence.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12022084", "endSection": "sections.0" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1049, "text": "GBP is a drug which is free of unwanted side effects. Its safety and tolerability profile is excellent for treatment of simple and complex partial crises, with or without generalization in epileptic patients of all ages.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12022084", "endSection": "sections.0" }, { "offsetInBeginSection": 168, "offsetInEndSection": 378, "text": "Two studies were conducted to determine the single-dose pharmacokinetics of gabapentin in healthy subjects age 1 month to 12 years and to guide dose selection in safety and efficacy trials in pediatric patients", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11361047", "endSection": "sections.0" }, { "offsetInBeginSection": 612, "offsetInEndSection": 689, "text": "Single doses of gabapentin were well tolerated by healthy pediatric subjects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11361047", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The efficacy and safety of gabapentin as add-on therapy for refractory partial seizures in 237 children, aged 3 to 12 years were evaluated over a 6-month period.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11305405", "endSection": "sections.0" }, { "offsetInBeginSection": 655, "offsetInEndSection": 739, "text": "Thirteen patients (5%) withdrew during the 6-month period because of adverse events.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11305405", "endSection": "sections.0" }, { "offsetInBeginSection": 457, "offsetInEndSection": 626, "text": "Male or female patients, at least 12 years old, with a recent history of partial seizures with or without secondary generalization, were randomized to receive gabapentin", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11274308", "endSection": "sections.0" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1256, "text": "Of the four most common adverse events (somnolence, dizziness, ataxia, fatigue), only one, dizziness, occurred more often in the nontitrated (Rapid initiation) group than in the titrated (Slow initiation) group.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11274308", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Twenty-six children with intellectual disability and six normal children, all suffering from refractory partial seizures, received open-label gabapentin (range = 10-50 mg kg(-1) day(-1); mean = 26.7 mg kg(-1) day(-1) as an add-on medication to their antiepileptic drug regimen", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10030434", "endSection": "sections.0" }, { "offsetInBeginSection": 768, "offsetInEndSection": 1371, "text": "In the present patient population, patients younger than 10 years of age, all of whom had intellectual disability, were more likely to have side-effects than those older than 10 years of age. Observed adverse effects, which were generally mild, occurred in patients with baseline intellectual disability, attention deficit disorder and behavioural problems. Behavioural adverse effects warranted discontinuation of the medication in only three patients. The severity of intellectual disability (mild versus moderate or severe) did not affect the extent of the response or the occurrence of side-effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10030434", "endSection": "sections.0" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1703, "text": "However, children with intellectual disability who also are less than 10 years of age with baseline attention deficit appear to be at a higher risk of behavioural side-effects.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10030434", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Efficacy and safety of gabapentin monotherapy were evaluated in 33 children with newly diagnosed absence epilepsy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9120226", "endSection": "sections.0" }, { "offsetInBeginSection": 712, "offsetInEndSection": 928, "text": "Somnolence and dizziness were the only adverse events reported by at least two patients during gabapentin treatment. No clinically important changes in laboratory assessments or other safety parameters were observed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9120226", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Thirty-two children with refractory partial epilepsy received open-label gabapentin as an additional medication to their antiepileptic drug regimen", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8648543", "endSection": "sections.0" }, { "offsetInBeginSection": 757, "offsetInEndSection": 950, "text": "The major reported side effects were behavioral. These consisted of hyperactivity, irritability, and agitation that occurred in patients with baseline mental retardation with attention deficit.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8648543", "endSection": "sections.0" }, { "offsetInBeginSection": 176, "offsetInEndSection": 454, "text": "We report 2 children who received GBP for intractable seizures and who developed intolerable aggressive behavior requiring dose reduction or drug discontinuation. Behavioral changes should be recognized as a possible side effect of GBP, especially in mentally retarded children.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8617181", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 564, "text": "We report 7 children who received gabapentin (GBP) as adjunctive medic ation and subsequently developed behavioral side effects. These behavioral changes consisted of intensification of baseline behaviors as well as new behavioral problems. Behaviors that parents considered most troublesome were tantrums, aggression directed toward others, hyperactivity, and defiance. All behavioral changes were reversible and were managed by dose reduction or discontinuation of GBP. All children had baseline attention deficit hyperactivity disorder and developmental delays.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8603631", "endSection": "sections.0" }, { "offsetInBeginSection": 88, "offsetInEndSection": 511, "text": "We described 3 learning disabled children, 1 aged 7 and 2 aged 10 years, with intractable partial seizures who developed severe behavioral problems while receiving modest doses of GBP. The children became hyperactive and had explosive outburst consisting of aggressive and oppositional behavior. The behavioral problems were sufficiently severe to require discontinuation of GBP despite moderately improved seizure control.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7489697", "endSection": "sections.0" } ] }, { "body": "What is the effect of ranolazine in diastolic heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17027025", "http://www.ncbi.nlm.nih.gov/pubmed/18439620", "http://www.ncbi.nlm.nih.gov/pubmed/24251065", "http://www.ncbi.nlm.nih.gov/pubmed/7873471", "http://www.ncbi.nlm.nih.gov/pubmed/19403851", "http://www.ncbi.nlm.nih.gov/pubmed/19333133", "http://www.ncbi.nlm.nih.gov/pubmed/22343711", "http://www.ncbi.nlm.nih.gov/pubmed/22465693", "http://www.ncbi.nlm.nih.gov/pubmed/21538388", "http://www.ncbi.nlm.nih.gov/pubmed/20924097", "http://www.ncbi.nlm.nih.gov/pubmed/22767404", "http://www.ncbi.nlm.nih.gov/pubmed/23596505", "http://www.ncbi.nlm.nih.gov/pubmed/19752362" ], "ideal_answer": [ "Data from in vitro and animal studies indicate that ranolazine improves diastolic function by inhibiting the late sodium current. Ranolazine is an innovative anti-ischemic and antianginal agent that reduces the Na-dependent Ca-overload, which improves diastolic tone and oxygen handling during myocardial ischemia. Furthermore, ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054144", "http://www.biosemantics.org/jochem#4202863" ], "type": "summary", "id": "532f05a5d6d3ac6a34000025", "snippets": [ { "offsetInBeginSection": 253, "offsetInEndSection": 383, "text": "Data from in vitro and animal studies indicate that ranolazine improves diastolic function by inhibiting the late sodium current. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21538388", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 384, "text": "Ranolazine is an innovative anti-ischemic and antianginal agent that inhibits the late Na current, thereby reducing the Na-dependent Ca-overload, which improves diastolic tone and oxygen handling during myocardial ischemia. In addition, ranolazine seems to exert beneficial effects on diastolic cardiac function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22767404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343711", "endSection": "title" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1799, "text": "Diastolic dysfunction could be reversed by ranolazine, probably resulting from a direct effect on myofilaments, indicating that cardiac oxidative stress may mediate diastolic dysfunction through altering the contractile apparatus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343711", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 981, "text": "Ranolazine (10 microM) significantly reduced the PC-induced increase in LVEDP by 72 +/- 6% (n = 6, p < 0.001), reduced left ventricular wall stiffness, and attenuated the PC-induced increase of CPP by 53 +/- 10% (n = 6-7, p < 0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19403851", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 804, "text": " Ranolazine, a specific inhibitor of late INa, reduces Na influx and hence ameliorates disturbed Na and Ca homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333133", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1288, "text": "New clinical and experimental studies even point to potential antiarrhythmic effects, beneficial effects in diastolic heart failure, and under hyperglycemic conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333133", "endSection": "abstract" } ] }, { "body": "Elaborate on the potential efficacy of gemcitabine for the treatment of recurrent, platinum-resistant epithelial ovarian cancer.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22468744", "http://www.ncbi.nlm.nih.gov/pubmed/16804928", "http://www.ncbi.nlm.nih.gov/pubmed/23679284", "http://www.ncbi.nlm.nih.gov/pubmed/15839957", "http://www.ncbi.nlm.nih.gov/pubmed/24185383", "http://www.ncbi.nlm.nih.gov/pubmed/16343176", "http://www.ncbi.nlm.nih.gov/pubmed/17966166", "http://www.ncbi.nlm.nih.gov/pubmed/18463961", "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "http://www.ncbi.nlm.nih.gov/pubmed/19469626", "http://www.ncbi.nlm.nih.gov/pubmed/23927758", "http://www.ncbi.nlm.nih.gov/pubmed/18073158", "http://www.ncbi.nlm.nih.gov/pubmed/19955917", "http://www.ncbi.nlm.nih.gov/pubmed/18336401", "http://www.ncbi.nlm.nih.gov/pubmed/19901115", "http://www.ncbi.nlm.nih.gov/pubmed/12449041", "http://www.ncbi.nlm.nih.gov/pubmed/16360545", "http://www.ncbi.nlm.nih.gov/pubmed/17938703", "http://www.ncbi.nlm.nih.gov/pubmed/12448655", "http://www.ncbi.nlm.nih.gov/pubmed/10964992" ], "ideal_answer": [ "Gemcitabine is a novel agent that has shown consistent activity as a single agent in the treatment of platinum-resistant ovarian cancer and a favorable toxicity profile. Because of its clinical and preclinical synergism with platinum analogs, gemcitabine has been combined with carboplatin as a convincing approach in the treatment of platinum-sensitive recurrent ovarian cancer patients. Gemcitabine and prolonged oral etoposide have shown reproducible single-agent activity in patients with platinum/paclitaxel-resistant ovarian cancer. The combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone. A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer. Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer. Gemcitabine plus endostar significantly improved the prognosis in patients with platinum-resistant recurrent ovarian cancer, especially in those with malignant effusion. Though the endostar cohort also improved median OS by 2.1 months, there was no statistically significant difference compared with gemcitabine alone cohort in this case." ], "concepts": [ "http://www.biosemantics.org/jochem#4260819", "http://www.biosemantics.org/jochem#4202605", "http://www.disease-ontology.org/api/metadata/DOID:2394" ], "type": "summary", "id": "553c8fd1f32186855800000a", "snippets": [ { "offsetInBeginSection": 1535, "offsetInEndSection": 1749, "text": "Gemcitabine and carboplatin demonstrate moderate toxicity with similar efficacy in both platinum-sensitive and platinum-resistant epithelial ovarian cancer, suggesting reversal of platinum resistance by gemcitabine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185383", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Gemcitabine-oxaliplatin (GEMOX) as salvage treatment in pretreated epithelial ovarian cancer patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23927758", "endSection": "title" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1764, "text": "GEMOX showed encouraging activity and manageable toxicity. Under circumstances requiring a rapid disease control, this combination regimen may offer a particularly viable option, particularly in heavily pretreated patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23927758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Salvage therapy of gemcitabine plus endostar significantly improves progression-free survival (PFS) with platinum-resistant recurrent epithelial ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679284", "endSection": "title" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1199, "text": "Gemcitabine plus endostar significantly improved the prognosis in patients with platinum-resistant recurrent ovarian cancer, especially in those with malignant effusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679284", "endSection": "abstract" }, { "offsetInBeginSection": 732, "offsetInEndSection": 899, "text": "Though the endostar cohort also improved median OS by 2.1 months, there was no statistically significant difference compared with gemcitabine alone cohort in this case", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679284", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 125, "text": "Gemcitabine based combination chemotherapy, a new salvage regimen for recurrent platinum resistant epithelial ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "endSection": "title" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1258, "text": "The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1729, "text": " the combination of gemcitabine and carboplatin is now approved for patients with platinum-sensitive recurrent ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19955917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901115", "endSection": "title" }, { "offsetInBeginSection": 1687, "offsetInEndSection": 1784, "text": "Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901115", "endSection": "abstract" }, { "offsetInBeginSection": 1371, "offsetInEndSection": 1553, "text": "The combination of gemcitabine and PLD is an effective and tolerable treatment option, with 74.3 % disease control rate for patients with platinum resistant/refractory ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19469626", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 169, "text": "Both gemcitabine and pegylated liposomal doxorubicin (PLD) are antineoplastic drugs with clinical activity in patients with platinum-resistant ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463961", "endSection": "abstract" }, { "offsetInBeginSection": 1319, "offsetInEndSection": 1521, "text": "A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463961", "endSection": "abstract" }, { "offsetInBeginSection": 2157, "offsetInEndSection": 2327, "text": "the combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17938703", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 274, "text": "Gemcitabine is a novel agent that has shown consistent activity as a single agent in the treatment of platinum-resistant ovarian cancer and a favorable toxicity profile", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16343176", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 493, "text": "Because of its clinical and preclinical synergism with platinum analogs, gemcitabine has been combined with carboplatin as a convincing approach in the treatment of platinum-sensitive recurrent ovarian cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16343176", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 553, "text": "Gemcitabine is a new antimetabolite selected for clinical trials based on its activity in preclinical studies. With response rates ranging from 11% to 22% in monotherapy in resistant or platinum refractory diseases, gemcitabine has quickly been shown to be an active agent in the treatment of patients with refractory recurrent ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12449041", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 296, "text": " Gemcitabine and prolonged oral etoposide have shown reproducible single-agent activity in patients with platinum/paclitaxel-resistant ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12448655", "endSection": "abstract" }, { "offsetInBeginSection": 1691, "offsetInEndSection": 1887, "text": "Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17966166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "[Gemcitabine based combination chemotherapy, a new salvage regimen for recurrent platinum resistant epithelial ovarian cancer].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "endSection": "title" }, { "offsetInBeginSection": 1506, "offsetInEndSection": 1722, "text": "Gemcitabine and carboplatin demonstrate moderate toxicity with similar efficacy in both platinum-sensitive and platinum-resistant epithelial ovarian cancer, suggesting reversal of platinum resistance by gemcitabine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24185383", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Efficacy and toxicity of gemcitabine and pegylated liposomal Doxorubicin in recurrent platinum-resistant/refractory epithelial ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19469626", "endSection": "title" }, { "offsetInBeginSection": 1620, "offsetInEndSection": 1817, "text": "Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17966166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Salvage therapy of gemcitabine plus endostar significantly improves progression-free survival (PFS) with platinum-resistant recurrent epithelial ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679284", "endSection": "title" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1207, "text": "The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "To evaluate the efficacy and toxicities of gemcitabine combined with ifosfamide and anthracycline chemotherapy for recurrent platinum resistant ovarian epithelial cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "A pilot study evaluating the efficacy and toxicity of biweekly gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant epithelial ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463961", "endSection": "title" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1259, "text": "CONCLUSION: The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17966166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Gemcitabine combined with oxaliplatin (GEMOX) as salvage treatment in elderly patients with advanced ovarian cancer refractory or resistant to platinum: a single institution experience.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18073158", "endSection": "title" }, { "offsetInBeginSection": 1653, "offsetInEndSection": 1850, "text": "Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17966166", "endSection": "abstract" } ] }, { "body": "How does Foxa transcription factor exhibits its pioneering function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "http://www.ncbi.nlm.nih.gov/pubmed/22406422", "http://www.ncbi.nlm.nih.gov/pubmed/21502411", "http://www.ncbi.nlm.nih.gov/pubmed/20591647", "http://www.ncbi.nlm.nih.gov/pubmed/16909212", "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "http://www.ncbi.nlm.nih.gov/pubmed/21404180", "http://www.ncbi.nlm.nih.gov/pubmed/21935353" ], "ideal_answer": [ "The conceptional framework of the mechanism of action of the FoxA proteins is that these 'pioneer factors' that can engage chromatin before other transcription factors. The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably. FoxA induces local DNA demethylation, nucleosome destabilization and binds to mitotic chromosomes. When associated with mitotic chromatin, FoxA may \"bookmark\" active genes and ensure their reactivation in postmitotic cells (epigenetic memory). About one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. The \"pioneer\" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and distinguish the factors with respect to their regulatory and mechanistic functions.", "FoxA proteins are pioneer transcription factors, among the first to bind chromatin domains in development and enable gene activity. There exists a hierarchy by which transcription factors can engage their target sites in chromatin, in that a subset of factors can bind transcriptionally silent, nucleosomal DNA, whereas most factors cannot, and this hierarchy is reflected, at least in part, in the developmental function of the factors. These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors." ], "type": "summary", "id": "57092f9bcf1c32585100001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a \"Bookmarking\" Oncoprotein that Alters the Host Cell Epigenotype?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "title" }, { "offsetInBeginSection": 364, "offsetInEndSection": 537, "text": "In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 650, "text": "Both EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 906, "text": "In addition, EBNA1 and FoxA, when associated with mitotic chromatin may \"bookmark\" active genes and ensure their reactivation in postmitotic cells (epigenetic memory)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 385, "text": "about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21935353", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 779, "text": "We found one such target site at a cryptic \"shadow\" enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21935353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Nuclear mobility and mitotic chromosome binding: similarities between pioneer transcription factor FoxA and linker histone H1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21502411", "endSection": "title" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1327, "text": "The results indicate that the \"pioneer\" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and that distinguish the factors with respect to their regulatory and mechanistic functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21502411", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 420, "text": "These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20591647", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1184, "text": "The purpose of this review is to critically examine the literature on three highly potent transcriptional activators: the herpes virus protein, VP16; the master regulator of skeletal muscle differentiation, MyoD and the \"pioneer\" factor for hepatogenesis, FoxA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21404180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "endSection": "title" }, { "offsetInBeginSection": 420, "offsetInEndSection": 684, "text": "We find that slower nuclear mobility correlates with high nonspecific nucleosome binding, and point mutations that disrupt nonspecific binding markedly increase nuclear mobility. FoxA's distinct nuclear mobility is consistent with its pioneer activity in chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 225, "text": "The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1233, "text": "Insight into the unique molecular basis of Foxa function has been obtained from recent genetic and genomic data, which identify the Foxa proteins as 'pioneer factors' whose binding to promoters and enhancers enable chromatin access for other tissue-specific transcription factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16909212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "endSection": "title" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1263, "text": "FOXO proteins represent a hybrid subclass having dual roles as pioneering factors and transcription factors. A subset of FOX proteins interacts with condensed mitotic chromatin and may function as 'bookmarking' agents to maintain transcriptional competence at specific genomic sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "There exists a hierarchy by which transcription factors can engage their target sites in chromatin, in that a subset of factors can bind transcriptionally silent, nucleosomal DNA, whereas most factors cannot, and this hierarchy is reflected, at least in part, in the developmental function of the factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21502411", "endSection": "abstract" } ] }, { "body": "Which are the 3 basic transcription factors that have been used for the direct reprogramming of fibroblasts into cardiomyocytes or cardiomyocyte like-cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23722259", "http://www.ncbi.nlm.nih.gov/pubmed/20691899", "http://www.ncbi.nlm.nih.gov/pubmed/22575762", "http://www.ncbi.nlm.nih.gov/pubmed/22522929", "http://www.ncbi.nlm.nih.gov/pubmed/21241459", "http://www.ncbi.nlm.nih.gov/pubmed/23704920", "http://www.ncbi.nlm.nih.gov/pubmed/23474887", "http://www.ncbi.nlm.nih.gov/pubmed/23050819", "http://www.ncbi.nlm.nih.gov/pubmed/23487791", "http://www.ncbi.nlm.nih.gov/pubmed/23861494", "http://www.ncbi.nlm.nih.gov/pubmed/22581928", "http://www.ncbi.nlm.nih.gov/pubmed/23591016" ], "ideal_answer": [ "Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We found that functional cardiomyocytes can be directly induced from fibroblasts by a combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5, in vitro and in vivo.", "Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported previously that induced cardiomyocyte-like cells (iCMs) can be directly generated from mouse cardiac fibroblasts in vitro and vivo by transduction of three transcription factors: Gata4, Mef2c, and Tbx5, collectively termed GMT. ", "Cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously." ], "exact_answer": [ [ "Gata4" ], [ "Mef2c" ], [ "Tbx5" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032383", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065150" ], "type": "list", "id": "54fb5c69d176fff445000003", "snippets": [ { "offsetInBeginSection": 186, "offsetInEndSection": 545, "text": "Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported previously that induced cardiomyocyte-like cells (iCMs) can be directly generated from mouse cardiac fibroblasts in vitro and vivo by transduction of three transcription factors: Gata4, Mef2c, and Tbx5, collectively termed GMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23861494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Cardiac fibroblasts can be reprogrammed to cardiomyocyte-like cells by the introduction of three transcription factors: Gata4, Mef2c and Tbx5 (collectively referred to here as GMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23722259", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1233, "text": "Here we describe a detailed step-by-step protocol for in vitro cardiac reprogramming using retroviruses encoding GMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23722259", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 781, "text": "Overexpression of transcription factors MYOCD and SRF alone or in conjunction with Mesp1 and SMARCD3 enhanced the basal but necessary cardio-inducing effect of the previously reported GATA4, TBX5, and MEF2C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704920", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1578, "text": " Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persist for weeks following inactivation of reprogramming factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591016", "endSection": "abstract" }, { "offsetInBeginSection": 670, "offsetInEndSection": 909, "text": "Here we show that four human cardiac transcription factors, including GATA binding protein 4, Hand2, T-box5, and myocardin, and two microRNAs, miR-1 and miR-133, activated cardiac marker expression in neonatal and adult human fibroblasts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23487791", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1033, "text": "We found that functional cardiomyocytes can be directly induced from fibroblasts by a combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5, in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474887", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 310, "text": "To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581928", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 842, "text": " In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581928", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 933, "text": "Here, to identify a cardiac transcription factor combination facilitating mouse fibroblast reprogramming into cardiomyocytes, we directly screened all triplet combinations of 10 candidate factors combined with a Q-PCR assay reporting induction of multiple cardiac-specific genes. Through this screening method the combination of Tbx5, Mef2c, and Myocd was identified to upregulate a broader spectrum of cardiac genes compared to the combination of Tbx5, Mef2c, and Gata4 that was recently shown to induce reprogramming of fibroblasts into cardiomyocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22575762", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 372, "text": "We reported previously that cardiac fibroblasts,which represent 50%of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522929", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 765, "text": "Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c, and Tbx5) rapidly and efficiently reprogrammed postnatal cardiac or dermal fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691899", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 507, "text": "More recently, we showed that reprogramming of cardiac fibroblasts to cardiomyocyte-like cells in vivo after coronary artery ligation using three cardiac transcription factors (Gata4/Mef2c/Tbx5) offers an alternative approach to regenerate heart muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23050819", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 612, "text": "Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c, and Tbx5) rapidly and efficiently reprogrammed postnatal cardiac or dermal fibroblasts directly into differentiated cardiomyocyte-like cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691899", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 782, "text": "Srivastava's group reported the first direct reprogramming of mouse fibroblast cells into mesoderm lineage cells (cardiomyocytes) with the enforced expression of three cardiac transcriptional factors: Gata4, Mef2c, and Tbx5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21241459", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 781, "text": "Srivastava's group reported the first direct reprogramming of mouse fibroblast cells into mesoderm lineage cells (cardiomyocytes) with the enforced expression of three cardiac transcriptional factors: Gata4, Mef2c, and Tbx5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21241459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Cardiac fibroblasts can be reprogrammed to cardiomyocyte-like cells by the introduction of three transcription factors: Gata4, Mef2c and Tbx5 (collectively referred to here as GMT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23722259", "endSection": "abstract" } ] }, { "body": "What is the name of Bruton's tyrosine kinase inhibitor that can be used for treatment of chronic lymphocytic leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "http://www.ncbi.nlm.nih.gov/pubmed/24085367", "http://www.ncbi.nlm.nih.gov/pubmed/24157582", "http://www.ncbi.nlm.nih.gov/pubmed/22960555", "http://www.ncbi.nlm.nih.gov/pubmed/24009233", "http://www.ncbi.nlm.nih.gov/pubmed/23619564", "http://www.ncbi.nlm.nih.gov/pubmed/22300471", "http://www.ncbi.nlm.nih.gov/pubmed/23617325", "http://www.ncbi.nlm.nih.gov/pubmed/23782158", "http://www.ncbi.nlm.nih.gov/pubmed/23359016", "http://www.ncbi.nlm.nih.gov/pubmed/24311722", "http://www.ncbi.nlm.nih.gov/pubmed/22830347", "http://www.ncbi.nlm.nih.gov/pubmed/23656200" ], "ideal_answer": [ "Ibrutinib is the covalent inhibitor of Bruton's tyrosine kinase that can be used for treatment of chronic lymphocytic leukemia (CLL). Ibrutinib has shown highly encouraging results in phase I/II trials in patients with treatment-naive, relapsed and refractory CLL even in the presence of high risk disease or poor prognostic markers. Ibrutinib demonstrated that Bruton's tyrosine kinase inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior. Ibrutinib has excellent activity in other B cell malignancies, including in particular mantle cell lymphoma and Waldenstrom macroglobulinemia." ], "exact_answer": [ "Ibrutinib" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007945", "http://www.uniprot.org/uniprot/BTK_CHICK", "http://www.uniprot.org/uniprot/IBTK_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.uniprot.org/uniprot/IBTK_XENLA", "http://www.uniprot.org/uniprot/BTK_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011505", "http://www.uniprot.org/uniprot/IBTK_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015451", "http://www.uniprot.org/uniprot/BTK_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:1040", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030292" ], "type": "factoid", "id": "530cf4c54a5037880c000008", "snippets": [ { "offsetInBeginSection": 187, "offsetInEndSection": 620, "text": "Bruton's tyrosine kinase (BTK) shows constitutive activity in CLL and is the target of irreversible inhibition by ibrutinib, an orally bioavailable kinase inhibitor that has shown outstanding activity in CLL. Early clinical results in CLL with other reversible and irreversible BTK inhibitors have been less promising, however, raising the question of whether BTK kinase activity is an important target of ibrutinib and also in CLL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311722", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1152, "text": "Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311722", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 473, "text": "Ibrutinib, an inhibitor of Bruton's tyrosine kinase is showing impressive responses in heavily pre-treated high-risk CLL, whether alone or in combination with MoAbs or chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157582", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1113, "text": "Ibrutinib acts by inhibiting the Bruton's tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24085367", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1261, "text": "Furthermore, we demonstrate that the Bruton's tyrosine kinase inhibitor ibrutinib or the PI3K inhibitor idelalisib block B-cell receptor induced activation of LCP1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24009233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23782158", "endSection": "title" }, { "offsetInBeginSection": 319, "offsetInEndSection": 625, "text": "We conducted a phase 1b-2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23782158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Recent clinical data suggest remarkable activity of ibrutinib, the first-in-class covalent inhibitor of Bruton's tyrosine kinase (BTK), in chronic lymphocytic leukemia (CLL), as well as excellent activity in other B cell malignancies, including in particular mantle cell lymphoma and Waldenstrom macroglobulinemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23656200", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 997, "text": "Next, we used this model to study ibrutinib, a Bruton's tyrosine kinase inhibitor in clinical development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23619564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Ibrutinib: a novel Bruton's tyrosine kinase inhibitor with outstanding responses in patients with chronic lymphocytic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23617325", "endSection": "title" }, { "offsetInBeginSection": 368, "offsetInEndSection": 607, "text": "Ibrutinib, a Bruton's tyrosine kinase inhibitor, has shown highly encouraging results in phase I/II trials in patients with treatment-naive, relapsed and refractory CLL even in the presence of high risk disease or poor prognostic markers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23617325", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1078, "text": "The compounds that are currently investigated in patients with CLL include ibrutinib -inhibitor of Btk, fostamatinib-inhibitor of Syk and idelalisib (GS-1101) -a specific isoform of the PI3K (PI3K) inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 600, "text": "Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359016", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1315, "text": "Small molecule inhibitors of BCR signaling kinases, Bruton's tyrosine kinase (Btk) inhibitor ibrutinib and the phosphoinositide 3'-kinase delta (PI3K\u03b4) inhibitor GS-1101, are currently transforming the landscape of CLL therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960555", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 938, "text": "More recently, several KIs have been developed to target the proximal B-cell receptor (BCR) signaling pathway including spleen tyrosine kinase inhibitor (Fostamatinib) and Bruton's tyrosine kinase inhibitors (Ibrutinib, AVL-263). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22830347", "endSection": "abstract" } ] }, { "body": "Is physical performance influenced by thyroid hormone metabolism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19468264", "http://www.ncbi.nlm.nih.gov/pubmed/2704923", "http://www.ncbi.nlm.nih.gov/pubmed/18523407", "http://www.ncbi.nlm.nih.gov/pubmed/16174720", "http://www.ncbi.nlm.nih.gov/pubmed/17893267", "http://www.ncbi.nlm.nih.gov/pubmed/16621071", "http://www.ncbi.nlm.nih.gov/pubmed/16910873", "http://www.ncbi.nlm.nih.gov/pubmed/21875391" ], "ideal_answer": [ "Yes." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/THA_LITCT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0015349", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056892", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.biosemantics.org/jochem#4275389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=2000609", "http://www.uniprot.org/uniprot/NCOA6_MOUSE", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327", "http://www.uniprot.org/uniprot/THB_PAROL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004996", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003918", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002154", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042403", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.uniprot.org/uniprot/NCOA6_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.uniprot.org/uniprot/NCOA6_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006590", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ], "type": "yesno", "id": "5151b8efd24251bc0500007a", "snippets": [ { "offsetInBeginSection": 1073, "offsetInEndSection": 1223, "text": "Longitudinal analysis showed that in Eut men higher baseline FT4 was significantly (p = 0.02) predictive of a lower SPPB score at the 3-year follow-up", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875391", "endSection": "sections.0" }, { "offsetInBeginSection": 1238, "offsetInEndSection": 1337, "text": "Even a modest thyroid hormone excess is associated with a reduced physical function in elderly men.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875391", "endSection": "sections.0" }, { "offsetInBeginSection": 696, "offsetInEndSection": 827, "text": "Oral L-thyroxine treatment was started and at a 1-month follow-up examination, mental status and physical performance were improved", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18523407", "endSection": "sections.0" }, { "offsetInBeginSection": 1572, "offsetInEndSection": 1704, "text": "In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16174720", "endSection": "sections.0" }, { "offsetInBeginSection": 84, "offsetInEndSection": 177, "text": "She had generalised weakness of muscles, cold intolerance and a reduced physical performance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2704923", "endSection": "sections.0" }, { "offsetInBeginSection": 528, "offsetInEndSection": 641, "text": "Replacement therapy by oral administration of L-thyroxin resulted in a gradual improvement of the patient's state", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2704923", "endSection": "sections.0" }, { "offsetInBeginSection": 730, "offsetInEndSection": 813, "text": "multivariate analysis revealed that total T3 was an independent predictor of VO2max", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17893267", "endSection": "sections.0" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1142, "text": "changes in thyroid hormone were closely correlated to myocardial functional status in patients with heart failure.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17893267", "endSection": "sections.0" }, { "offsetInBeginSection": 1848, "offsetInEndSection": 1993, "text": "THR among patients with SCH is beneficial not only by improvement in lipid profile, as well as by improvement in cognitive and functional status,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16621071", "endSection": "sections.0" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1337, "text": "CONCLUSIONS: Even a modest thyroid hormone excess is associated with a reduced physical function in elderly men.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875391", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Subclinical hyperthyroidism (SH) may be responsible for many cardiovascular changes, including an impaired exercise performance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16910873", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND: Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16174720", "endSection": "sections.0" } ] }, { "body": "Do plant genomes contain CpG islands?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15733327", "http://www.ncbi.nlm.nih.gov/pubmed/12857799", "http://www.ncbi.nlm.nih.gov/pubmed/16283384", "http://www.ncbi.nlm.nih.gov/pubmed/12054347", "http://www.ncbi.nlm.nih.gov/pubmed/21548945", "http://www.ncbi.nlm.nih.gov/pubmed/11489175", "http://www.ncbi.nlm.nih.gov/pubmed/16453856" ], "ideal_answer": [ "In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster. Among them, class 1 genes, which harbor a CpG cluster at the 5 -terminus, share similarities with human genes having CpG islands ", "Yes. In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018745", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044404", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899" ], "type": "yesno", "id": "553d0005f321868558000011", "snippets": [ { "offsetInBeginSection": 1711, "offsetInEndSection": 2070, "text": "This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster. Among them, class 1 genes, which harbor a CpG cluster at the 5'-terminus, share similarities with human genes having CpG islands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16283384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Segmental distribution of genes harboring a CpG island-like region on rice chromosomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16283384", "endSection": "title" }, { "offsetInBeginSection": 1986, "offsetInEndSection": 2516, "text": "Highly-expressed Arabidopsis genes had overall a more marked GC-skew in the TSS compared to genes with low expression levels. We therefore propose that the GC-skew around the TSS in some plants and fungi is related to transcription. It might be caused by mutations during transcription initiation or the frequent use of transcription factor-biding sites having a strand preference. In addition, GC-skew is a good candidate index for TSS prediction in plant genomes, where there is a lack of correlation among CpG islands and genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15733327", "endSection": "abstract" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 2066, "text": "Preliminary analysis shows that promoter location based on the detection of potential CpG/CpNpG islands in the Arabidopsis genome is not straightforward. Nevertheless, because the landscape of CpG/CpNpG islands differs considerably between promoters and introns on the one side and exons (whether coding or not) on the other, more sophisticated approaches can probably be developed for the successful detection of \"putative\" CpG and CpNpG islands in plants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12857799", "endSection": "abstract" }, { "offsetInBeginSection": 1664, "offsetInEndSection": 2024, "text": "This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548945", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 818, "text": "These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11489175", "endSection": "abstract" }, { "offsetInBeginSection": 1698, "offsetInEndSection": 2071, "text": "CONCLUSIONS: This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16283384", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 826, "text": "These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11489175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Unmethylated CpG islands associated with genes in higher plant DNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16453856", "endSection": "title" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 2039, "text": "This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548945", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 825, "text": "These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11489175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "We screened plant genome sequences, primarily from rice and Arabidopsis thaliana, for CpG islands, and identified DNA segments rich in CpG dinucleotides within these sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11489175", "endSection": "abstract" } ] }, { "body": "Describe the isolation of transcription factor complexes by in vivo biotinylation tagging and direct binding to streptavidin beads, as applied for the case of the essential hematopoietic transcription factor GATA-1.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "http://www.ncbi.nlm.nih.gov/pubmed/16888367", "http://www.ncbi.nlm.nih.gov/pubmed/19196479" ], "ideal_answer": [ "Owing to the very high affinity of biotin for avidin and streptavidin, biotinylation tagging offers an attractive approach for the efficient purification of protein complexes. The very high affinity of the biotin/(strept)avidin system also offers the potential for the single-step capture of lower abundance protein complexes, such as transcription factor complexes. The identification of short peptide tags that are efficiently biotinylated by the bacterial BirA biotin ligase led to an approach for the single-step purification of transcription factor complexes by specific in vivo biotinylation tagging. A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1. The direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry. This led to the characterization of several distinct GATA-1 complexes with other transcription factors and chromatin remodeling cofactors, which are involved in activation and repression of gene targets. Thus, BirA-mediated tagging is an efficient approach for the direct capture and characterization of transcription factor complexes." ], "concepts": [ "http://www.biosemantics.org/jochem#4250381", "http://www.uniprot.org/uniprot/GATA1_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005488", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005667", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033613", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000989", "http://www.uniprot.org/uniprot/SAV_STRAV", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008134" ], "type": "summary", "id": "553a761cf321868558000001", "snippets": [ { "offsetInBeginSection": 750, "offsetInEndSection": 938, "text": "Using the biotin tagged erythroid transcription factor GATA-1 as example, we describe several optimization steps for the application of the high affinity biotin streptavidin system in ChIP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19196479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Isolation and characterization of hematopoietic transcription factor complexes by in vivo biotinylation tagging and mass spectrometry", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1519, "text": "Efficient tagging methodologies are an integral aspect of protein complex characterization by proteomic approaches. Owing to the very high affinity of biotin for avidin and streptavidin, biotinylation tagging offers an attractive approach for the efficient purification of protein complexes. The very high affinity of the biotin/(strept)avidin system also offers the potential for the single-step capture of lower abundance protein complexes, such as transcription factor complexes. The identification of short peptide tags that are efficiently biotinylated by the bacterial BirA biotin ligase led to an approach for the single-step purification of transcription factor complexes by specific in vivo biotinylation tagging. A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1. The direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry. This led to the characterization of several distinct GATA-1 complexes with other transcription factors and chromatin remodeling cofactors, which are involved in activation and repression of gene targets. Thus, BirA-mediated tagging is an efficient approach for the direct capture and characterization of transcription factor complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16888367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "We have described the application of a simple biotinylation tagging approach for the direct purification of tagged transcription factor complexes, based on the use of artificial short peptide tags that are specifically and efficiently biotinylated by the bacterial BirA biotin ligase, which is co-expressed in cells with the tagged factor. We used this approach to initially characterize complexes formed by the hematopoietic transcription factor GATA-1 in erythroid cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 557, "text": "Epitope tags have often been used as more reliable alternatives. In addition, we have employed protein in vivo biotinylation tagging as a very high affinity alternative to antibodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19196479", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 663, "text": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 965, "text": "A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16888367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Isolation and characterization of hematopoietic transcription factor complexes by in vivo biotinylation tagging and mass spectrometry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16339652", "endSection": "title" }, { "offsetInBeginSection": 723, "offsetInEndSection": 969, "text": "A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16888367", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1184, "text": "The direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16888367", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 665, "text": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 664, "text": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920471", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 968, "text": "A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16888367", "endSection": "abstract" } ] }, { "body": "Are high-flow nasal cannulae effective for treatment of preterm infants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21563154", "http://www.ncbi.nlm.nih.gov/pubmed/24225220", "http://www.ncbi.nlm.nih.gov/pubmed/22518179", "http://www.ncbi.nlm.nih.gov/pubmed/24106935", "http://www.ncbi.nlm.nih.gov/pubmed/23782410", "http://www.ncbi.nlm.nih.gov/pubmed/23143331", "http://www.ncbi.nlm.nih.gov/pubmed/21276671", "http://www.ncbi.nlm.nih.gov/pubmed/23955516", "http://www.ncbi.nlm.nih.gov/pubmed/21682982", "http://www.ncbi.nlm.nih.gov/pubmed/22958022", "http://www.ncbi.nlm.nih.gov/pubmed/23947111", "http://www.ncbi.nlm.nih.gov/pubmed/23903677", "http://www.ncbi.nlm.nih.gov/pubmed/23260098", "http://www.ncbi.nlm.nih.gov/pubmed/23114244", "http://www.ncbi.nlm.nih.gov/pubmed/22173399", "http://www.ncbi.nlm.nih.gov/pubmed/17989697", "http://www.ncbi.nlm.nih.gov/pubmed/19762171", "http://www.ncbi.nlm.nih.gov/pubmed/11331690", "http://www.ncbi.nlm.nih.gov/pubmed/22964658" ], "ideal_answer": [ "Yes. The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure for noninvasive respiratory support of preterm infants after extubation. However, the use of high-flow nasal cannulae in preterm infants was shown to be associated with a higher rate of reintubation, increased exposure to oxygen and longer duration of respiratory support. High-flow nasal cannulae are also effective for treatment of apnea of prematurity." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057785", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000281", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007234" ], "type": "yesno", "id": "530cf4c54a5037880c000002", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 245, "text": "The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106935", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1244, "text": "The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, -1.9 to 18.7). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106935", "endSection": "abstract" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1832, "text": "Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106935", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 627, "text": "Recently high flow nasal cannula (HFNC) is emerging as an efficient, better tolerated form of NIV, allowing better access to the baby's face, which may improve nursing, feeding and bonding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23947111", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1179, "text": "In conclusion, there is a growing evidence of the feasibility of HFNC as an alternative mode of NIV. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23947111", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1104, "text": "HHHFNC and NCPAP produced similar rates of extubation failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23260098", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 287, "text": "The use of HFNC as a respiratory support modality is increasing in the infant, pediatric, and adult populations as an alternative to non-invasive positive pressure ventilation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23143331", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1452, "text": "Current evidence suggests that HFNC is well tolerated and may be feasible in a subset of patients who require ventilatory support with non-invasive ventilation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23143331", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 137, "text": "Heated, humidified, high-flow nasal cannula oxygen therapy (HHHFNC) has been used to improve ventilation in preterm infants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23114244", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1532, "text": "Increasing flow rates of HHHFNC therapy are associated with linear increases in NP pressures in bronchiolitis patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23114244", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 534, "text": "An alternative to the use of nasal continuous positive airway pressure (NCPAP) as a non-invasive modality to support respiratory distress in premature infants has been the recent introduction of high flow nasal cannula (HFNC) devices in many neonatal units. There has been increased use of HFNC presumably because of anecdotal reports and experience that it is easy to use, and well tolerated by the infants, while experiencing decreased nasal septumerosion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22958022", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 186, "text": "High-flow nasal cannulae (HFNC) are gaining in popularity as a form of non-invasive respiratory support for preterm infants in neonatal intensive care units around the world.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22964658", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1102, "text": "HFNC may be as effective as NCPAP at improving respiratory parameters such as tidal volume and work of breathing in preterm infants, but probably only at flow rates >2 litres/min. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22964658", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1325, "text": "There is growing evidence of the feasibility of HFNC as an alternative to other forms of non-invasive ventilation in preterm infants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22964658", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1793, "text": "When used as primary respiratory support after birth, one trial found similar rates of treatment failure in infants treated with HFNC and nasal CPAP. Following extubation, one trial found that infants treated with HFNC had a significantly higher rate of reintubation than those treated with nasal CPAP. Another trial found similar rates of reintubation for humidified and non-humidified HFNC, and the fourth trial found no difference between two different models of equipment used to deliver humidified HFNC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21563154", "endSection": "abstract" }, { "offsetInBeginSection": 1948, "offsetInEndSection": 2055, "text": "When used following extubation, HFNC may be associated with a higher rate of reintubation than nasal CPAP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21563154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Early weaning from CPAP to high flow nasal cannula in preterm infants is associated with prolonged oxygen requirement: a randomized controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276671", "endSection": "title" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1372, "text": "After randomization, the no-NC group had fewer days on oxygen [median (interquartile range): 5 (1-8) vs 14 (7.5-19.25) days, p<0.001] and shorter duration of respiratory support [10.5 (4-21) vs 18 (11.5-29) days, p=0.03]. There were no differences between groups regarding success of weaning from NCPAP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276671", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1517, "text": "Weaning preterm infants from NCPAP to NC is associated with increased exposure to oxygen and longer duration of respiratory support.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276671", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 350, "text": "A number of centers use high-flow nasal cannula (HFNC) in the management of AOP without measuring the positive distending pressure (PDP) generated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11331690", "endSection": "abstract" }, { "offsetInBeginSection": 1645, "offsetInEndSection": 1700, "text": "HFNC is as effective as NCPAP in the management of AOP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11331690", "endSection": "abstract" } ] }, { "body": "What are the molecular characteristics of the FAA (FANCA) cDNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8896563" ], "ideal_answer": [ "The 5.5-kb cDNA of the FAA (FANCA) gene has an open reading frame of 4,368 nucleotides, whereas the FAA protein is predicted to have a molecular weight of approximately 163 kDa." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052217", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018076" ], "type": "summary", "id": "54edf1ee94afd6150400000f", "snippets": [ { "offsetInBeginSection": 789, "offsetInEndSection": 1265, "text": "Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8896563", "endSection": "abstract" } ] }, { "body": "What are the skeletal muscle satellite cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21339173", "http://www.ncbi.nlm.nih.gov/pubmed/17996437", "http://www.ncbi.nlm.nih.gov/pubmed/17600112", "http://www.ncbi.nlm.nih.gov/pubmed/22233500", "http://www.ncbi.nlm.nih.gov/pubmed/21727135", "http://www.ncbi.nlm.nih.gov/pubmed/26055324", "http://www.ncbi.nlm.nih.gov/pubmed/24747722", "http://www.ncbi.nlm.nih.gov/pubmed/19265661", "http://www.ncbi.nlm.nih.gov/pubmed/25732238", "http://www.ncbi.nlm.nih.gov/pubmed/26248268", "http://www.ncbi.nlm.nih.gov/pubmed/12757751", "http://www.ncbi.nlm.nih.gov/pubmed/24439806", "http://www.ncbi.nlm.nih.gov/pubmed/26074812", "http://www.ncbi.nlm.nih.gov/pubmed/26341996" ], "ideal_answer": [ "Skeletal muscle satellite cells (SCs) are Pax7(+) myogenic stem cells that reside between the basal lamina and the plasmalemma of the myofiber. In mature muscles, SCs are typically quiescent, but can be activated in response to muscle injury. Depending on the magnitude of tissue trauma, SCs may divide minimally to repair subtle damage within individual myofibers or produce a larger progeny pool that forms new myofibers in cases of overt muscle injury", "Skeletal muscle satellite cells (SCs) are Pax7(+) myogenic stem cells that reside between the basal lamina and the plasmalemma of the myofiber. In mature muscles, SCs are typically quiescent, but can be activated in response to muscle injury. Depending on the magnitude of tissue trauma, SCs may divide minimally to repair subtle damage within individual myofibers or produce a larger progeny pool that forms new myofibers in cases of overt muscle injury." ], "type": "summary", "id": "571f356f0fd6f91b68000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "Skeletal muscle satellite cells (SCs) are Pax7(+) myogenic stem cells that reside between the basal lamina and the plasmalemma of the myofiber. In mature muscles, SCs are typically quiescent, but can be activated in response to muscle injury. Depending on the magnitude of tissue trauma, SCs may divide minimally to repair subtle damage within individual myofibers or produce a larger progeny pool that forms new myofibers in cases of overt muscle injury", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26074812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Satellite cells (SC) are quiescent adult muscle stem cells critical for postnatal development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25732238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Satellite cells are multipotential stem cells that mediate postnatal muscle growth and respond differently to temperature based upon aerobic versus anaerobic fiber-type origin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26341996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 493, "text": "Skeletal muscle mass, function, and repair capacity all progressively decline with aging, restricting mobility, voluntary function, and quality of life. Skeletal muscle repair is facilitated by a population of dedicated muscle stem cells (MuSCs), also known as satellite cells, that reside in anatomically defined niches within muscle tissues. In adult tissues, MuSCs are retained in a quiescent state until they are primed to regenerate damaged muscle through cycles of self-renewal divisions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26248268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Muscle satellite cells are a stem cell population required for postnatal skeletal muscle development and regeneration, accounting for 2-5% of sublaminal nuclei in muscle fibers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24747722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Skeletal muscle satellite cells are adult muscle-derived stem cells receiving increasing attention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22233500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Skeletal muscle satellite cells are quiescent mononucleated myogenic cells, located between the sarcolemma and basement membrane of terminally-differentiated muscle fibres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "The acquisition of a proliferating-cell status from a quiescent state as well as the shift between proliferation and differentiation are key developmental steps in skeletal-muscle stem cells (satellite cells) to provide proper muscle regeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26055324", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 275, "text": "Satellite cells are essential for skeletal muscle regeneration as they ultimately provide the myogenic precursors that rebuild damaged muscle tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Skeletal muscle satellite cells are committed to myogenesis and do not spontaneously adopt nonmyogenic fates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21339173", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 367, "text": "These are normally quiescent in adult muscle, but act as a reserve population of cells, able to proliferate in response to injury and give rise to regenerated muscle and to more satellite cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757751", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 853, "text": "Satellite cell-derived muscle precursor cells may be used to repair and regenerate damaged or myopathic skeletal muscle, or to act as vectors for gene therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Research focusing on the canonical adult myogenic progenitor, the skeletal muscle satellite cell, is still an ever-growing field 46 years from their initial description.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17996437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 390, "text": " Skeletal muscle satellite cells, located between the basal lamina and plasma membrane of myofibers, are required for skeletal muscle regeneration. The capacity of satellite cells as well as other cell lineages including mesoangioblasts, mesenchymal stem cells, and side population (SP) cells to contribute to muscle regeneration has complicated the identification of a satellite stem cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19265661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": " Muscle satellite cells are a stem cell population required for postnatal skeletal muscle development and regeneration, accounting for 2-5% of sublaminal nuclei in muscle fibers. In adult muscle, satellite cells are normally mitotically quiescent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24747722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 377, "text": " Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21727135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": " Skeletal muscle satellite cells are adult muscle-derived stem cells receiving increasing attention. Sheep satellite cells have a greater similarity to human satellite cells with regard to metabolism, life span, proliferation and differentiation, than satellite cells of the rat and mouse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22233500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Skeletal muscle satellite cells are adult muscle-derived stem cells receiving increasing attention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22233500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Skeletal muscle satellite cells play key roles in postnatal muscle growth and regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17600112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Muscle satellite cells are a stem cell population required for postnatal skeletal muscle development and regeneration, accounting for 2-5% of sublaminal nuclei in muscle fibers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24747722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Skeletal muscle satellite cells are quiescent mononucleated myogenic cells, located between the sarcolemma and basement membrane of terminally-differentiated muscle fibres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Skeletal muscle satellite cells, located between the basal lamina and plasma membrane of myofibers, are required for skeletal muscle regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19265661", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 377, "text": "Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21727135", "endSection": "abstract" } ] }, { "body": "What is the role of neurogranin in Alzheimer's disease patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20875798", "http://www.ncbi.nlm.nih.gov/pubmed/15851848", "http://www.ncbi.nlm.nih.gov/pubmed/26136856", "http://www.ncbi.nlm.nih.gov/pubmed/24978200" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8417448", "o": "D051579" } ], "ideal_answer": [ "Dendritic protein neurogranin is markedly increased in cerebrospinal fluid in Alzheimer's disease patients. Neurogranin might reflect the neurodegenerative processes within the brain, indicating a role for neurogranin as a potential novel clinical biomarker for synaptic degeneration in AD.\nNeurogranin is important for synaptic plasticity and memory." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "http://www.uniprot.org/uniprot/NEUG_BOVIN", "http://www.uniprot.org/uniprot/NEUG_CAPHI", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051579", "http://www.biosemantics.org/jochem#4250477", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.uniprot.org/uniprot/NEUG_MOUSE", "http://www.uniprot.org/uniprot/NEUG_SERCA", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380" ], "type": "summary", "id": "56bce51cd36b5da37800000a", "snippets": [ { "offsetInBeginSection": 279, "offsetInEndSection": 519, "text": "We recently showed that the dendritic protein neurogranin (Ng), including the endogenous Ng peptide 48 to 76 (Ng48-76), is markedly increased in cerebrospinal fluid (CSF) in AD and that Ng48-76 is the dominant peptide in human brain tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26136856", "endSection": "abstract" }, { "offsetInBeginSection": 1791, "offsetInEndSection": 1915, "text": "In agreement with previous studies, we show that CSF Ng is significantly increased in AD as compared with healthy controls. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26136856", "endSection": "abstract" }, { "offsetInBeginSection": 2011, "offsetInEndSection": 2224, "text": "The results suggest that CSF Ng, in particular Ng48-76, might reflect the neurodegenerative processes within the brain, indicating a role for Ng as a potential novel clinical biomarker for synaptic function in AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26136856", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1091, "text": " These modifications were associated with impaired spatial memory and reduced hippocampal expression of signaling molecules important for synaptic plasticity and memory, including neurogranin, CaMKII, ERK, GSK3\u03b2, CREB, and expression of the transcription factor EGR1/Zif268. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24978200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875798", "endSection": "title" }, { "offsetInBeginSection": 520, "offsetInEndSection": 721, "text": "Relative quantification revealed a significant increase of neurogranin in the AD group compared with controls, while the MCI group was not statistically different from either controls or the AD group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875798", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1469, "text": "The elevated neurogranin levels in the MCI and AD groups might reflect synaptic degeneration. These results together suggest that cerebrospinal fluid neurogranin might be valuable together with the established AD biomarkers in the early diagnosis of AD and warrants further studies to determine the diagnostic value of neurogranin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875798", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 522, "text": "Further, to determine whether presynaptic or postsynaptic compartments of neurons are preferentially affected in AD patients, we studied 3 presynaptic vesicle proteins (synaptotagmin, synaptophysin, and Rab 3A), 2 synaptic membrane proteins (Gap 43 and synaptobrevin), and 2 postsynaptic proteins (neurogranin and synaptopodin) in specimens from AD and age-matched control brains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851848", "endSection": "abstract" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1609, "text": "Our study suggests that postsynaptic proteins and presynaptic proteins are important for synaptic function and may be related to cognitive impairments in AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851848", "endSection": "abstract" }, { "offsetInBeginSection": 1462, "offsetInEndSection": 1699, "text": "These results together suggest that cerebrospinal fluid neurogranin might be valuable together with the established AD biomarkers in the early diagnosis of AD and warrants further studies to determine the diagnostic value of neurogranin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20875798", "endSection": "title" }, { "offsetInBeginSection": 265, "offsetInEndSection": 505, "text": "We recently showed that the dendritic protein neurogranin (Ng), including the endogenous Ng peptide 48 to 76 (Ng48-76), is markedly increased in cerebrospinal fluid (CSF) in AD and that Ng48-76 is the dominant peptide in human brain tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26136856", "endSection": "abstract" } ] }, { "body": "Does triiodothyronine play a regulatory role in insulin secretion from pancreas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17408701", "http://www.ncbi.nlm.nih.gov/pubmed/21099301", "http://www.ncbi.nlm.nih.gov/pubmed/1357067", "http://www.ncbi.nlm.nih.gov/pubmed/619228", "http://www.ncbi.nlm.nih.gov/pubmed/19021014", "http://www.ncbi.nlm.nih.gov/pubmed/20730704", "http://www.ncbi.nlm.nih.gov/pubmed/3310493", "http://www.ncbi.nlm.nih.gov/pubmed/1537314", "http://www.ncbi.nlm.nih.gov/pubmed/21914860", "http://www.ncbi.nlm.nih.gov/pubmed/2242013" ], "ideal_answer": [ "YES" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/INS_DANRE", "http://www.biosemantics.org/jochem#4054676", "http://www.uniprot.org/uniprot/INS_HORSE", "http://www.uniprot.org/uniprot/INS_LOPAM", "http://www.uniprot.org/uniprot/INS_CANFA", "http://www.uniprot.org/uniprot/INS_PANBU", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0050796", "http://www.uniprot.org/uniprot/INS_MYOSC", "http://www.biosemantics.org/jochem#4275389", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/INS_APLCA", "http://www.biosemantics.org/jochem#4249447", "http://www.uniprot.org/uniprot/INS_CHICH", "http://www.uniprot.org/uniprot/INS_CHICK", "http://www.uniprot.org/uniprot/INS_HYSCR", "http://www.uniprot.org/uniprot/INS_ORENI", "http://www.uniprot.org/uniprot/INS_LAMFL", "http://www.uniprot.org/uniprot/INS_VERMO", "http://www.uniprot.org/uniprot/INS_LOPPI", "http://www.uniprot.org/uniprot/INS_CAVPO", "http://www.uniprot.org/uniprot/INS_AOTTR", "http://www.uniprot.org/uniprot/INS_OCTDE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007328", "http://www.uniprot.org/uniprot/INS_CAPHI", "http://www.uniprot.org/uniprot/INS_RODSP", "http://www.uniprot.org/uniprot/INS_SQUAC", "http://www.uniprot.org/uniprot/INS_CAMDR", "http://www.uniprot.org/uniprot/INS_CALMI", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061385", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0030073", "http://www.uniprot.org/uniprot/INS_PHYMC", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0032024", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010179", "http://www.uniprot.org/uniprot/INS_SHEEP", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046676", "http://www.uniprot.org/uniprot/INS_PIAME", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050417", "http://www.uniprot.org/uniprot/INS_ORNAN", "http://www.uniprot.org/uniprot/INS_ATRSP", "http://www.uniprot.org/uniprot/INS_GADMC", "http://www.uniprot.org/uniprot/INS_CAIMO" ], "type": "yesno", "id": "51682382298dcd4e51000066", "snippets": [ { "offsetInBeginSection": 1105, "offsetInEndSection": 1320, "text": "Our findings establish that p43 is an important regulator of glucose homeostasis and pancreatic \u03b2-cell function and provide evidence for the first time of a physiological role for a mitochondrial endocrine receptor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21914860", "endSection": "sections.0" }, { "offsetInBeginSection": 492, "offsetInEndSection": 648, "text": "The p43(-/-) mice had a major defect in insulin secretion both in vivo and in isolated pancreatic islets and a loss of glucose-stimulated insulin secretion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21914860", "endSection": "sections.0" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1083, "text": "We demonstrated that treatment of primary cultures of rat pancreatic islets with T3 results in augmented \u03b2-cell vitality with an increase of their functional properties.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21099301", "endSection": "sections.0" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1344, "text": "Nonetheless, the insulin secretion is sensibly augmented after T3 stimulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21099301", "endSection": "sections.0" }, { "offsetInBeginSection": 681, "offsetInEndSection": 946, "text": "Plasma glucose concentration of the fetal hypothyroid group during intravenous glucose tolerance test was significantly higher (p=0.003) at 5-20 min as compared to the control group, whereas plasma insulin concentration was significantly lower (p=0.012) at 5-20 min", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730704", "endSection": "sections.0" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1340, "text": "Although adult offspring born from hypothyroid mothers were euthyroid, their glucose tolerance and glucose stimulated insulin secretion of islets were altered", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730704", "endSection": "sections.0" }, { "offsetInBeginSection": 1, "offsetInEndSection": 87, "text": "hyroid hormones modulate the immune system and metabolism, influence insulin secretion", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19021014", "endSection": "sections.0" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1190, "text": "Only T(3) concentrations higher than 250 microM were able to decrease cell viability and proliferation rate, to increase the rate of apoptosis and to reduce glucose-induced insulin secretion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17408701", "endSection": "sections.0" }, { "offsetInBeginSection": 359, "offsetInEndSection": 735, "text": "Islets preincubated with glucose (3.3 mmol/l) and glucagon (1.4 mumol/l) plus theophylline (10 mmol/l), ACTH (0.11 nmol/l), bovine GH (0.46 mumol/l), prolactin (0.2 mumol/l) or tri-iodothyronine (1.0 nmol/l) have significantly lower Ca(2+)-ATPase activity than those preincubated with only 3.3 mmol glucose/l. All these hormones increased the release of insulin significantly.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1357067", "endSection": "sections.0" }, { "offsetInBeginSection": 1326, "offsetInEndSection": 1476, "text": "T3 (0.2 nM) did not affect insulin secretion in the absence or presence of glucose or in the presence of secretagogues (potassium and glyceraldehyde).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1537314", "endSection": "sections.0" }, { "offsetInBeginSection": 202, "offsetInEndSection": 373, "text": "In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2242013", "endSection": "sections.0" }, { "offsetInBeginSection": 374, "offsetInEndSection": 541, "text": "The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2242013", "endSection": "sections.0" }, { "offsetInBeginSection": 626, "offsetInEndSection": 1003, "text": "Addition of T3 to the incubation medium, significantly modified the insulin release, but its effect varied according to the glucose concentration in the medium, i.e. it enhanced the insulin release at a glucose concentration between 2 to 8 mmol/l; it has no effect at 12 mmol/glucose, and significantly inhibited the secretion of insulin in the presence of 16.6 mmol/l glucose.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3310493", "endSection": "sections.0" }, { "offsetInBeginSection": 588, "offsetInEndSection": 630, "text": "Both T3 and T4 inhibited insulin secretion", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/619228", "endSection": "sections.0" } ] }, { "body": "How many disulfide bridges has the protein hepcidin got?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11985602", "http://www.ncbi.nlm.nih.gov/pubmed/21838701", "http://www.ncbi.nlm.nih.gov/pubmed/22967859", "http://www.ncbi.nlm.nih.gov/pubmed/21073997", "http://www.ncbi.nlm.nih.gov/pubmed/22705624", "http://www.ncbi.nlm.nih.gov/pubmed/24018861" ], "ideal_answer": [ "Hepcidin contains eight cysteine residues that form four disulfide bridges." ], "exact_answer": [ "Hepcidin contains eight cysteine residues that form four disulfide bridges" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004220", "http://www.uniprot.org/uniprot/HEPC_RAT", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064451" ], "type": "factoid", "id": "54f2210164850a5854000001", "snippets": [ { "offsetInBeginSection": 356, "offsetInEndSection": 400, "text": " hepcidin, containing four disulfide bridges", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24018861", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 629, "text": "Cshepc has eight cysteines formed four conserved disulfide bridges, similarly to that of human's", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22967859", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 313, "text": "The native peptide of 25 amino acids (Hepc25) contains four disulfide bridges that maintain a \u03b2-hairpin motif.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22705624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Hepcidin, a 25 amino acid peptide hormone containing a complex network of four disulfide bonds is the hormone regulator of iron homeostasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838701", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 622, "text": "Molecular mass measurements of the native peptide and the reduced and alkylated peptide confirmed the sequence with four intramolecular disulfide bridges. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11985602", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 575, "text": "Hepcidin contains eight cysteine residues that form four disulfide bridges, which stabilize a hairpin-shaped structure with two beta sheets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073997", "endSection": "abstract" } ] }, { "body": "What is the association between GERD and gluten ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20601132", "http://www.ncbi.nlm.nih.gov/pubmed/23567359", "http://www.ncbi.nlm.nih.gov/pubmed/15316418", "http://www.ncbi.nlm.nih.gov/pubmed/21438963", "http://www.ncbi.nlm.nih.gov/pubmed/18853995" ], "ideal_answer": [ "GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.\nFood intolerance is a common complaint amongst patients with functional gastrointestinal (GI) disorders (FGIDs), including those with irritable bowel syndrome (IBS), functional dyspepsia, as well as gastroesophageal reflux disease. There is a great interest in the role of a major dietary protein, gluten, in the production of symptoms...several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002446", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005983", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005764", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055050" ], "type": "summary", "id": "5324d12b9b2d7acc7e000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Food intolerance is a common complaint amongst patients with functional gastrointestinal (GI) disorders (FGIDs), including those with irritable bowel syndrome (IBS), functional dyspepsia, as well as gastroesophageal reflux disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567359", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 998, "text": "There is a great interest in the role of a major dietary protein, gluten, in the production of symptoms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23567359", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 586, "text": "several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21438963", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 1023, "text": "Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21438963", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 253, "text": "Celiac disease (CD) patients often complain of symptoms consistent with gastroesophageal reflux disease (GERD). We aimed to assess the prevalence of GERD symptoms at diagnosis and to determine the impact of the gluten-free diet (GFD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601132", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 720, "text": ": At diagnosis, celiac patients had a significantly higher reflux symptom mean score than healthy controls (P < .001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601132", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 949, "text": "Moderate to severe symptoms were significantly associated with the classical clinical presentation of CD (35.0%) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601132", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1382, "text": "GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20601132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Effect of gluten-free diet on preventing recurrence of gastroesophageal reflux disease-related symptoms in adult celiac patients with nonerosive reflux disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18853995", "endSection": "title" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1350, "text": "The present study is the first to have evaluated the effect of a GFD in the nonerosive form of GERD in CD patients, by means of clinical long-term follow-up, suggesting that GFD could be a useful approach in reducing GERD symptoms and in the prevention of recurrence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18853995", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1187, "text": "Altogether, 0.9% of patients with oesophagitis and 0.6% of those with oesophageal reflux symptoms had coeliac disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316418", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1399, "text": "The prevalence of oesophagitis was 5.2% in untreated coeliac disease, 5.6% in treated coeliac disease,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316418", "endSection": "abstract" }, { "offsetInBeginSection": 1472, "offsetInEndSection": 1578, "text": "In coeliac patients, the reflux symptoms were mild but nevertheless were alleviated on a gluten-free diet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316418", "endSection": "abstract" }, { "offsetInBeginSection": 1725, "offsetInEndSection": 1885, "text": "The association between these two conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for reflux symptoms in coeliac disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316418", "endSection": "abstract" } ] }, { "body": "Which are the major intramolecular phosphorylation sites of human Chk2 involved in cell cycle control?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18812180" ], "ideal_answer": [ "The major phosphorylation sites of human Chk2 involved in cell cycle control are T68, S19, and S33/35." ], "exact_answer": [ [ "T68" ], [ "S19" ], [ "S33/35" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010766", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064447", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016310", "http://www.uniprot.org/uniprot/CHK2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006468", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042325", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001932" ], "type": "list", "id": "5357b9bcf1005d6b58000008", "snippets": [ { "offsetInBeginSection": 697, "offsetInEndSection": 889, "text": "Transfection of HEK293 cells with Chk2 wildtype and Chk2 mutants in the absence or presence of DNA damage showed significant T68 phosphorylation already in the absence of DNA damaging reagents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812180", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 975, "text": "Upon DNA damage, phosphorylation of additional Chk2 sites was observed (S19, S33/35)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812180", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 888, "text": "Transfection of HEK293 cells with Chk2 wildtype and Chk2 mutants in the absence or presence of DNA damage showed significant T68 phosphorylation already in the absence of DNA damaging reagents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812180", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 974, "text": "Upon DNA damage, phosphorylation of additional Chk2 sites was observed (S19, S33/35)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812180", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 500, "text": "Despite distinct time-dependent autophosphorylation kinetics by monitoring the phosphorylation of amino acid residues T68, S19, S33/35, T432, in Chk2 wildtype and Chk2 mutants (T68A, T68D and Q69E) they gave identical specific activities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812180", "endSection": "abstract" } ] }, { "body": "Is the Histidine-Rich Calcium Binding protein (HRC) related to arrhythmias and cardiac disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15191886", "http://www.ncbi.nlm.nih.gov/pubmed/17030629", "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "http://www.ncbi.nlm.nih.gov/pubmed/24125847", "http://www.ncbi.nlm.nih.gov/pubmed/19403607", "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "http://www.ncbi.nlm.nih.gov/pubmed/22040806", "http://www.ncbi.nlm.nih.gov/pubmed/18617481" ], "ideal_answer": [ "Histidine-rich calcium binding protein (HRC) is a high capacity, low affinity Ca(2+) binding protein with a potential role in heart failure and arrhythmogenesis due to its activity as regulator of SR Ca(2+) uptake and Ca(2+) release.In addition, HRC null mice displayed a significantly exaggerated response to the induction of cardiac hypertrophy by isoproterenol compared to their wild-type littermates. A human genetic variant (Ser96Ala) in HRC has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.biosemantics.org/jochem#4263030" ], "type": "yesno", "id": "54f482d264850a5854000009", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 212, "text": "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24125847", "endSection": "abstract" }, { "offsetInBeginSection": 1817, "offsetInEndSection": 1998, "text": "These findings suggest that aberrant SR Ca2+ release and increased susceptibility to delayed afterdepolarizations underlie triggered arrhythmic activity in human Ala96 HRC carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24125847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1525, "text": "These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742996", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1403, "text": "HRC plays an important role in myocyte differentiation and in antiapoptotic cardioprotection against ischemia/reperfusion induced cardiac injury. Interestingly, HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1575, "text": "This review summarizes studies, which have established the critical role of HRC in Ca(2+)-homeostasis, suggesting its importance in cardiac physiology and pathophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 1193, "text": "HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk between SR Ca(2+) uptake and release. Indeed, evidence from genetic models of JCN and HRC indicate that they are important in cardiophysiology as alterations in these proteins affect SR Ca(2+) handling and cardiac function. In addition, downregulation of JCN and HRC may contribute to Ca(2+) cycling perturbations manifest in the failing heart, where their protein levels are significantly reduced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19403607", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1423, "text": "The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18617481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "AAV-mediated knock-down of HRC exacerbates transverse aorta constriction-induced heart failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "endSection": "title" }, { "offsetInBeginSection": 191, "offsetInEndSection": 323, "text": "Chronic overexpression of HRC that may disrupt intracellular Ca(2+) homeostasis is implicated in pathogenesis of cardiac hypertrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 499, "text": "Ablation of HRC showed relatively normal phenotypes under basal condition, but exhibited a significantly increased susceptibility to isoproterenol-induced cardiac hypertrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "endSection": "abstract" }, { "offsetInBeginSection": 1949, "offsetInEndSection": 2095, "text": "Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through perturbed SR-mediated Ca(2+) cycling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1441, "text": "However, AAV9-mediated HRC-KD in TAC-FH was associated with decreased fractional shortening and increased cardiac fibrosis compared with control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22952658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 448, "text": "Histidine-rich calcium binding protein (HRC) is a high capacity, low affinity Ca(2+) binding protein, specifically expressed in striated muscles of mammals. In rabbit skeletal and cardiac muscles, HRC binds to sarcoplasmic reticulum (SR) membranes via triadin, a junctional SR protein. Recently, a potential role in heart failure and arrhythmogenesis has been assigned to HRC due to its activity as regulator of SR Ca(2+) uptake and Ca(2+) release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22040806", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1488, "text": "In addition, HRC null mice displayed a significantly exaggerated response to the induction of cardiac hypertrophy by isoproterenol compared to their wild-type littermates. The exaggerated response of HRC knockout mice to the induction of cardiac hypertrophy is consistent with a regulatory role for HRCBP in calcium handling in vivo and suggests that mutations in HRC, in combination with other genetic or environmental factors, might contribute to pathological hypertrophy and heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17030629", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 377, "text": "We observed that the levels of HRC were reduced in animal models and human heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15191886", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1456, "text": "Collectively, these data indicate that alterations in expression levels of HRC are associated with impaired cardiac SR Ca homeostasis and contractile function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15191886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Abnormal calcium cycling and cardiac arrhythmias associated with the human Ser96Ala genetic variant of histidine-rich calcium-binding protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24125847", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18617481", "endSection": "title" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1402, "text": "Interestingly, HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807542", "endSection": "abstract" } ] }, { "body": "Which are the methods for in silico prediction of the origin of replication (ori) among bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18582175", "http://www.ncbi.nlm.nih.gov/pubmed/23093601", "http://www.ncbi.nlm.nih.gov/pubmed/18237442", "http://www.ncbi.nlm.nih.gov/pubmed/24822028", "http://www.ncbi.nlm.nih.gov/pubmed/12218031", "http://www.ncbi.nlm.nih.gov/pubmed/25309521", "http://www.ncbi.nlm.nih.gov/pubmed/17188685", "http://www.ncbi.nlm.nih.gov/pubmed/14643658", "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "http://www.ncbi.nlm.nih.gov/pubmed/21945744", "http://www.ncbi.nlm.nih.gov/pubmed/17584494", "http://www.ncbi.nlm.nih.gov/pubmed/24808892", "http://www.ncbi.nlm.nih.gov/pubmed/19332823", "http://www.ncbi.nlm.nih.gov/pubmed/12732098" ], "ideal_answer": [ "Several in silico methods have been applied for prediction of the origin of replication (ori). DNA base composition asymmetry, such as GC skew, is the basis of numerous in silico methods used to detect the ori in prokaryotes. The Z curve analysis is also used for ori identification. Comparative genomics, by BLAST analyses of the intergenic sequences compared to related species have been applied in ori prediction. The finding of the dnaA gene and its binding sites, DnaA boxes, as well as the finding of the binding sites of other proteins, such as CtrA and IHF, are fundamental characteristics used for in silico prediction of the ori. Also, the localization of boundary genes, such as cell division cycle (cdc6) gene, and consensus origin recognition box (ORB) sequences have been employed for ori detection. The study of the gene order around the origin sequence and the distribution of the genes encoded in the leading versus the lagging strand are also used for in silico detection of the ori." ], "exact_answer": [ [ "GC skew analysis" ], [ "Z curve analysis" ], [ "comparative genomics" ], [ "dnaA gene location" ], [ "localization of dnaA binding sites (DnaA boxes)" ], [ "localization of CtrA binding sites" ], [ "localization of IHF binding sites" ], [ "localization of cell division cycle (cdc6) gene" ], [ "localization of other boundary genes" ], [ "localization of other consensus origin recognition box (ORB) sequences" ], [ "the gene order around the ori" ], [ "gene distribution in leading versus lagging strand" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000808", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003688", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018741" ], "type": "list", "id": "5542644fed966d112c000004", "snippets": [ { "offsetInBeginSection": 522, "offsetInEndSection": 715, "text": "Based on the Z-curve theory, we have developed a web-based system Ori-Finder to predict oriCs in bacterial genomes with high accuracy and reliability by taking advantage of comparative genomics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23093601", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 935, "text": "we have applied a combination of multiple in silico approaches - Z curve, the cell division cycle (cdc6) gene location and location of consensus origin recognition box (ORB) sequences for location of origin of replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 888, "text": "Using features that have been previously experimentally verified in the alpha-Proteobacterium Caulobacter crescentus, the origin of DNA replication (ori) regions were identified in silico for Wolbachia strains and eleven other related bacteria belonging to Ehrlichia, Anaplasma, and Rickettsia genera. These features include DnaA-, CtrA- and IHF-binding sites as well as the flanking genes in C. crescentus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584494", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1357, "text": "The sequences of the ori regions described here are only similar among closely related bacteria while fundamental characteristics like presence of DnaA and IHF binding sites as well as the boundary genes are more widely conserved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17584494", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 724, "text": "We propose a correlation measure and show that it is correctly able to predict the origin of replication in most of the bacterial genomes. When applied to Methanocaldococcus jannaschii, Plasmodium falciparum apicoplast and Nicotiana tabacum plastid, this correlation based method is able to correctly predict the origin of replication whereas the generally used GC skew measure fails.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21945744", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 415, "text": "DNA base composition asymmetry is the basis of numerous in silico methods used to detect the origin and terminus of replication in prokaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18582175", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1153, "text": "These analyses include finding the dnaA gene and its binding sites; making BLAST analyses of the intergenic sequences compared to related species; studying the gene order around the origin sequence; and studying the distribution of the genes encoded in the leading versus the lagging strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18582175", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 491, "text": "DnaA binds a single DnaA box as a monomer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14643658", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 613, "text": "In silico comparative analysis of sequenced mollicute genomes indicated the lack of conservation of gene order in the region containing the predicted origin of replication (oriC) and the existence, in most of the mollicute genomes examined, of putative DnaA boxes lying upstream and downstream from the dnaA gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218031", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 1090, "text": "In this paper we have applied a combination of multiple in silico approaches - Z curve, the cell division cycle (cdc6) gene location and location of consensus origin recognition box (ORB) sequences for location of origin of replication in Thermococcus onnurineus, Thermococcus gammatolerans and other Themococcales and compared the results to that of the well-documented case of Pyrococcus abyssi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364800", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 413, "text": "DNA base composition asymmetry is the basis of numerous in silico methods used to detect the origin and terminus of replication in prokaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18582175", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 737, "text": "It increases the prediction accuracy of the replication termini compared with previously documented methods based on genomic base composition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17188685", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 264, "text": "Using compositional skews such as the GC skew, replication origin and terminus can be predicted in silico by observing the shift points.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17188685", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1119, "text": "Here, we summarize the recent advances of in silico prediction of oriCs in bacterial and archaeal genomes using the Z-curve based method", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24822028", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 414, "text": "DNA base composition asymmetry is the basis of numerous in silico methods used to detect the origin and terminus of replication in prokaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18582175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Recent Advances in the Identification of Replication Origins Based on the Z-curve Method.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24822028", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 783, "text": "We present a web-based tool Ori-Finder 2 to predict oriCs in the archaeal genomes automatically, based on the integrated method comprising the analysis of base composition asymmetry using the Z-curve method, the distribution of origin recognition boxes identified by FIMO tool, and the occurrence of genes frequently close to oriCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309521", "endSection": "abstract" } ] }, { "body": "What is the use of emulsion PCR in Next Generation Sequencing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23398507", "http://www.ncbi.nlm.nih.gov/pubmed/22668416", "http://www.ncbi.nlm.nih.gov/pubmed/23148498", "http://www.ncbi.nlm.nih.gov/pubmed/23900195", "http://www.ncbi.nlm.nih.gov/pubmed/21513157", "http://www.ncbi.nlm.nih.gov/pubmed/21543404", "http://www.ncbi.nlm.nih.gov/pubmed/23546785", "http://www.ncbi.nlm.nih.gov/pubmed/23744319", "http://www.ncbi.nlm.nih.gov/pubmed/23665194", "http://www.ncbi.nlm.nih.gov/pubmed/22355625" ], "ideal_answer": [ "Prior to Next Generation Sequencing reactions, DNA libraries are constructed, amplified with emulsion PCR, and enriched with the use of enrichment beads. The library samples are then loaded to a sequencing chip and analyzed on an NGS platform." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016133", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004655", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017421" ], "type": "summary", "id": "5319a83bb166e2b80600002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Emulsion PCR-coupled target enrichment: an effective fishing method for high-throughput sequencing of poorly preserved ancient DNA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23900195", "endSection": "title" }, { "offsetInBeginSection": 325, "offsetInEndSection": 680, "text": "We present a unified strategy in which emulsion PCR is coupled with target enrichment followed by next-generation sequencing. The method made it possible to obtain efficiently non-duplicated reads mapped to target sequences of interest, and this can achieve deep and reliable sequencing of ancient DNA from typical materials, even though poorly preserved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23900195", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 900, "text": "Three multiplex PCR reactions were carried out to amplify the coding exons of 328 genes including FBN1, TGFBR1 and TGFBR2. DNA fragments from different samples were ligated with barcoded sequencing adaptors. Template preparation and emulsion PCR, and Ion Sphere Particles enrichment were carried out using an Ion One Touch system. The ion sphere particles were sequenced on a 318 chip using the PGM platform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23744319", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1156, "text": "In our NGS approach, the 16,569-bp mtDNA is enriched by long-range PCR and the 108 nuclear genes (which represent 1301 amplicons and 680 kb) are enriched by RainDance emulsion PCR. Sequencing is performed on Illumina HiSeq 2000 or MiSeq platforms, and bioinformatics analysis is performed using commercial and in-house developed bioinformatics pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23665194", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 684, "text": "However, pyrosequencing of emulsion PCR reactions, amplifying from only one molecule at a time, can generate megabases of clonally amplified loci at high coverage, thereby greatly simplifying allelic sequence determination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23546785", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1319, "text": "During genomic PCR, in this 4-primer system, the outer set of primers containing the MID and the 454 adaptor sequences are incorporated into an amplicon generated by the inner HLA target-specific primers each containing a common sequence tag at the 5' end of the forward and reverse primers. Pools of the resulting amplicons are used for emulsion PCR and clonal sequencing on the 454 Life Sciences GS FLX System, followed by genotyping with Conexio software.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398507", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 724, "text": "The purpose of our study was to compare NGS enrichment methods for a clinical assay targeting the nine genes known to be associated with aortopathy. RainDance emulsion PCR and SureSelect RNA-bait hybridization capture enrichment methods were directly compared by enriching DNA from eight samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23148498", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1073, "text": "We show the efficacy by comparing the method to a commercial kit and further demonstrate that emulsion PCR can be used for bias free amplification and virtual immortalization of DNA template libraries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22668416", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 403, "text": "Here, we describe a novel approach for normalization of multiplex next generation sequencing libraries after emulsion PCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22355625", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 607, "text": "Briefly, amplified libraries carrying unique barcodes are prepared by fluorescent tagging of complementary sequences and then resolved by high-speed flow cytometric sorting of labeled emulsion PCR beads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22355625", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 959, "text": "The protocol is simple and provides an even sequence distribution of multiplex libraries when sequencing the flow-sorted beads. Moreover, since many empty and mixed emulsion PCR beads are removed, the approach gives rise to a substantial increase in sequence quality and mean read length, as compared to that obtained by standard enrichment protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22355625", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 307, "text": "Based on the mechanism of emulsion PCR, a unique DNA template would only generate a unique sequence read after being amplified and sequenced on GS FLX.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21543404", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 1015, "text": "Prior to SOLiD sequencing reaction, the libraries were amplified with emulsion PCR and enriched with the P2 enrichment beads. The library samples were loaded to sequencing Chip for Work Flow Analysis (WFA) or sequencing running with default parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21513157", "endSection": "abstract" } ] }, { "body": "Can adult humans be induced to produce fetal hemoglobin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24222332", "http://www.ncbi.nlm.nih.gov/pubmed/10908330", "http://www.ncbi.nlm.nih.gov/pubmed/22460946", "http://www.ncbi.nlm.nih.gov/pubmed/17041717", "http://www.ncbi.nlm.nih.gov/pubmed/11144280", "http://www.ncbi.nlm.nih.gov/pubmed/16939628", "http://www.ncbi.nlm.nih.gov/pubmed/10575541", "http://www.ncbi.nlm.nih.gov/pubmed/7541126", "http://www.ncbi.nlm.nih.gov/pubmed/20201948", "http://www.ncbi.nlm.nih.gov/pubmed/17486495", "http://www.ncbi.nlm.nih.gov/pubmed/14594506", "http://www.ncbi.nlm.nih.gov/pubmed/18379999", "http://www.ncbi.nlm.nih.gov/pubmed/21415990", "http://www.ncbi.nlm.nih.gov/pubmed/16735596", 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"http://purl.uniprot.org/pubmed/1639402" } ], "ideal_answer": [ "Fetal hemoglobin, or foetal haemoglobin, is the main oxygen transport protein in the human fetus during the last seven months of development in the uterus and in the newborn until roughly 6 months old. Functionally, fetal hemoglobin differs most from adult hemoglobin in that it is able to bind oxygen with greater affinity than the adult form, giving the developing fetus better access to oxygen from the mother's bloodstream.\nUnusually high levels of fetal haemoglobin production can ameliorate sickle cell disease and \u03b2 thalassaemia. Although efforts directed at the pharmacological stimulation of fetal haemoglobin as an approach to managing these conditions have met with limited success, there is wide variation in individual responses. \nBased on results, adults humans could be induced to produce fetal hemoglobin." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4249367", "http://www.uniprot.org/uniprot/GLB_APLLI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006454", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055545", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055544", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005344", "http://www.uniprot.org/uniprot/HBG_BRAAR", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002648", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005319", "http://www.biosemantics.org/jochem#4249310", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005914" ], "type": "yesno", "id": "531481ade3eabad021000016", "snippets": [ { "offsetInBeginSection": 243, "offsetInEndSection": 318, "text": " At the time of birth, HbF accounts for approximately 70% of the total Hb. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18379999", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 521, "text": " whereas in the trace amounts of HbF that is found in the adult it reverses to 40:60 because of a gamma- to beta-globin gene switch", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18379999", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 986, "text": "With the increased understanding and discovery of molecular regulators of haemoglobin switching, such as BCL11A, new avenues of research may lead ultimately to novel therapeutic, mechanism-based approaches to fetal haemoglobin reactivation in patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20201948", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1192, "text": "The data suggest that TGF-beta reactivates gamma-globin expression, combined with a sequential stimulation and suppression of erythropoiesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14594506", "endSection": "abstract" } ] }, { "body": "What is the role of thyroid hormone in Stem cell differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22890105", "http://www.ncbi.nlm.nih.gov/pubmed/20667986", "http://www.ncbi.nlm.nih.gov/pubmed/23937304", "http://www.ncbi.nlm.nih.gov/pubmed/22468949", "http://www.ncbi.nlm.nih.gov/pubmed/15450085", "http://www.ncbi.nlm.nih.gov/pubmed/23970787", "http://www.ncbi.nlm.nih.gov/pubmed/21896185", "http://www.ncbi.nlm.nih.gov/pubmed/9731697", "http://www.ncbi.nlm.nih.gov/pubmed/2298257", "http://www.ncbi.nlm.nih.gov/pubmed/22497336", "http://www.ncbi.nlm.nih.gov/pubmed/22560077", "http://www.ncbi.nlm.nih.gov/pubmed/15358620", "http://www.ncbi.nlm.nih.gov/pubmed/9687498", "http://www.ncbi.nlm.nih.gov/pubmed/20656376", "http://www.ncbi.nlm.nih.gov/pubmed/23832699", "http://www.ncbi.nlm.nih.gov/pubmed/15550503", "http://www.ncbi.nlm.nih.gov/pubmed/12072400", "http://www.ncbi.nlm.nih.gov/pubmed/15728663", "http://www.ncbi.nlm.nih.gov/pubmed/24013065", "http://www.ncbi.nlm.nih.gov/pubmed/22968643", "http://www.ncbi.nlm.nih.gov/pubmed/7935490" ], "ideal_answer": [ "Thyroid hormone treatment of Human-induced pluripotent stem cell-derived cardiomyocytes attenuates the fetal gene expression and induces differentiation. Liganded T3 receptor (TR) regulates cell autonomous formation of adult intestinal progenitor cells and that T3 action in the connective tissue is important for the establishment of the stem cell niche. In the intestinal epithelium, TR\u03b11 and TR\u03b22 are expressed at the level of stem/progenitor cell populations where they induce cell proliferation and differentiation, respectively. Thyroid hormone is implicated in neural stem cell function and differentiation and acts as a neurogenic switch in the adult neural stem cell niche. Furthermore, thyroid hormone enhances maturation of oligodendrocyte precursor cells. Thyroid hormones also induce hemopoietic pluripotent stem cell differentiation toward erythropoiesis and c-erbA/TR appears to act as a binary switch affecting erythroid cell fate: unliganded c-erbA/TR supports growth while ligand-activated c-erbA/TR induces differentiation. Finally, thyroid hormone modulates late differentiation stages of mesenchymal stem cells chondrogenesis via BMP signaling." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013234", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002454" ], "type": "summary", "id": "52ed27c098d0239505000030", "snippets": [ { "offsetInBeginSection": 730, "offsetInEndSection": 1095, "text": "During T3-dependent amphibian metamorphosis, the digestive tract is extensively remodeled from the larval to the adult form for the adaptation of the amphibian from its aquatic herbivorous lifestyle to that of a terrestrial carnivorous frog. This involves de novo formation of ASCs that requires T3 signaling in both the larval epithelium and nonepithelial tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23970787", "endSection": "abstract" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1580, "text": "Our results revealed that T3 induces distinct tissue-specific gene regulation programs associated with the remodeling of the intestine, particularly the formation of the ASCs, and further suggested the existence of potentially many novel stem cell-associated genes, at least in the intestine during development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23970787", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1511, "text": "BMP signaling is an important modulator of the late differentiation stages in MSC chondrogenesis and the thyroid hormone induces this pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23937304", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1440, "text": "In addition, thyroid hormone treatment of hiPS-CMs attenuated the fetal gene expression in favor of a more adult-like pattern. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23832699", "endSection": "abstract" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1306, "text": "Exposure of embryos at this developmental stage for 24 h to either a TH antagonist, NH-3, or to tetrabromobisphenol A, a flame retardant and known TH disruptor, differentially modulated the expression of a number of TH target genes implicated in neural stem cell function or neural differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968643", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1207, "text": "In the intestinal epithelium and the retina, TR\u03b11 and TR\u03b22 are expressed at the level of the precursors where they induce cell proliferation and differentiation, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22560077", "endSection": "title" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1496, "text": "We will discuss observations suggesting that liganded T3 receptor (TR) regulates cell autonomous formation of adult intestinal progenitor cells and that T3 action in the connective tissue is important for the establishment of the stem cell niche.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896185", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 270, "text": "In general, in vitro stem cell differentiation techniques stimulate a wide range of developmental programs, including thyroid hormone receptor (TR) pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15550503", "endSection": "abstract" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1417, "text": "Although no difference of in vitro proliferation of NSCs was observed in the presence of epidermal growth factor, maturation of oligodendrocytes (defined by process number and length) was enhanced in hyperthyroidism, suggesting a more mature state than in control animals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15450085", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 985, "text": "Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone (3,5,3'-triiodothyronine [T3]) to the differentiation medium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15358620", "endSection": "abstract" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1095, "text": "This resulted in highly synchronous differentiation of the cells toward enucleated erythrocytes within 6 days", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15358620", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 741, "text": "T(3) alone stimulated neural differentiation in a similar fashion as that seen with RA in both wtES and mES cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12072400", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 906, "text": "Thus, c-erbA/TR appears to act as a binary switch affecting erythroid cell fate: unliganded c-erbA/TR supports growth while ligand-activated c-erbA/TR induces differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The thyroid hormone receptor functions as a ligand-operated developmental switch between proliferation and differentiation of erythroid progenitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9687498", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Thyroid hormones induce hemopoietic pluripotent stem cell differentiation toward erythropoiesis ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2298257", "endSection": "title" } ] }, { "body": "Which receptors can be evaluated with the [18F]altanserin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22940693", "http://www.ncbi.nlm.nih.gov/pubmed/12902843", "http://www.ncbi.nlm.nih.gov/pubmed/16206185", "http://www.ncbi.nlm.nih.gov/pubmed/23824248", "http://www.ncbi.nlm.nih.gov/pubmed/20641567", "http://www.ncbi.nlm.nih.gov/pubmed/12642173", "http://www.ncbi.nlm.nih.gov/pubmed/17195073", "http://www.ncbi.nlm.nih.gov/pubmed/21098981", "http://www.ncbi.nlm.nih.gov/pubmed/7995287", "http://www.ncbi.nlm.nih.gov/pubmed/24120220", "http://www.ncbi.nlm.nih.gov/pubmed/21996132", "http://www.ncbi.nlm.nih.gov/pubmed/9027929", "http://www.ncbi.nlm.nih.gov/pubmed/21359565", "http://www.ncbi.nlm.nih.gov/pubmed/21722741", "http://www.ncbi.nlm.nih.gov/pubmed/21473029", "http://www.ncbi.nlm.nih.gov/pubmed/18828013", "http://www.ncbi.nlm.nih.gov/pubmed/17241616", "http://www.ncbi.nlm.nih.gov/pubmed/10587097", "http://www.ncbi.nlm.nih.gov/pubmed/19007894", "http://www.ncbi.nlm.nih.gov/pubmed/17541696", "http://www.ncbi.nlm.nih.gov/pubmed/23137806", "http://www.ncbi.nlm.nih.gov/pubmed/19162492", "http://www.ncbi.nlm.nih.gov/pubmed/20956470", "http://www.ncbi.nlm.nih.gov/pubmed/10688105", "http://www.ncbi.nlm.nih.gov/pubmed/19959344", "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "http://www.ncbi.nlm.nih.gov/pubmed/12224404", "http://www.ncbi.nlm.nih.gov/pubmed/15356424", "http://www.ncbi.nlm.nih.gov/pubmed/7673371", "http://www.ncbi.nlm.nih.gov/pubmed/23456885", "http://www.ncbi.nlm.nih.gov/pubmed/17185512", "http://www.ncbi.nlm.nih.gov/pubmed/19015089", "http://www.ncbi.nlm.nih.gov/pubmed/19353726", "http://www.ncbi.nlm.nih.gov/pubmed/21473027", "http://www.ncbi.nlm.nih.gov/pubmed/10588399", "http://www.ncbi.nlm.nih.gov/pubmed/23390031", "http://www.ncbi.nlm.nih.gov/pubmed/23303045", "http://www.ncbi.nlm.nih.gov/pubmed/21750562", "http://www.ncbi.nlm.nih.gov/pubmed/9257335", "http://www.ncbi.nlm.nih.gov/pubmed/1428914", "http://www.ncbi.nlm.nih.gov/pubmed/9824691" ], "ideal_answer": [ "5-HT2A (5-hydroxytryptamine type 2a) receptor can be evaluated with the [18F]altanserin." ], "exact_answer": [ "5-HT2A" ], "concepts": [ "http://www.biosemantics.org/jochem#4263650" ], "type": "factoid", "id": "55242d512c8b63434a000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "PURPOSE: While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23456885", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1138, "text": "CONCLUSION: [18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23456885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Imaging the cerebral serotonin 2A (5-HT2A ) receptors with positron emission tomography (PET) has been carried out in humans with [(11) C]MDL 100907 and [(18) F]altanserin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390031", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1348, "text": "The cortical binding of [(18) F]MH.MZ and [(18) F]altanserin was blocked by ketanserin supporting that both radioligands bind to 5-HT2A receptors in the pig brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390031", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 494, "text": "We investigated 94 healthy individuals (60 men, mean age 47.0\u00b118.7, range 23-86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [18F]-altanserin PET imaging. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23137806", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 802, "text": "Two hours after placebo/drug administration, 250 MBq of the 5-HT(2A) receptor selective PET-radiotracer [(18)F]altanserin was administered intravenously as a 30s bolus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21996132", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1921, "text": "These data suggest that the combination of a dexfenfluramine-induced 5-HT release and subsequent assessment of 5-HT(2A) receptor availability with [(18)F]altanserin PET is suitable to measure cortical 5-HT release capacity in the human brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21996132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The 5-hydroxytryptamine type 2a (5-HT(2A)) selective radiotracer [(18)F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750562", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 788, "text": "[(18)F]altanserin is suitable for quantification of 5-HT(2A) receptor availability in rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750562", "endSection": "abstract" }, { "offsetInBeginSection": 2262, "offsetInEndSection": 2662, "text": "Altanserin, a fluorobenzoyl derivative related to ketanserin, was reported to be a potent antagonist of 5-HT2A receptors with >100-fold selectivity over D2/3 receptors, 5-HT1A, 5-HT6, and 5-HT7 (9, 10). This led to the development of 3-{2-[4-(4-[(18)F]fluorobenzoyl)-1-piperidyl]ethyl}-2-sulfanyl-3H-quinazolin-4-one ([(18)F]altanserin) as a useful tool for 5-HT2A receptor PET imaging in vivo (11). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21473029", "endSection": "abstract" }, { "offsetInBeginSection": 2262, "offsetInEndSection": 2936, "text": "Altanserin, a fluorobenzoyl derivative related to ketanserin, was reported to be a potent antagonist of 5-HT2A receptors with >100-fold selectivity over D2/3 receptors, 5-HT1A, 5-HT6, and 5-HT7 (9, 10). This led to the development of 3-{2-[4-(4-[(18)F]fluorobenzoyl)-1-piperidyl]ethyl}-2-sulfanyl-3H-quinazolin-4-one ([(18)F]altanserin) as a useful tool for 5-HT2A receptor PET imaging in vivo (11). 5-HT2A antagonists bind to the total pool of receptors, whereas 5-HT2A agonists bind only to the high-affinity functional state of the receptor but may be more important in disease states because the high affinity sites are the ones that transmit the intracellular signals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21473027", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 478, "text": "Baseline and follow-up partial volume corrected levels of 5-HT2A in four neocortical lobes and the posterior cingulate gyrus were investigated using [18F]altanserin positron emission tomography with a bolus-infusion approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098981", "endSection": "abstract" }, { "offsetInBeginSection": 2240, "offsetInEndSection": 2637, "text": "Altanserin, a fluorobenzoyl derivative related to ketanserin, was reported to be a potent inhibitor of 5-HT2A receptors with >100-fold selectivity over D2/3 receptors, 5-HT1A, 5-HT6, and 5-HT7 (8, 9). This led to the development of 3-[2-[4-(4-[(18)F]fluorobenzoyl)-1-piperidyl]ethyl]-2-sulfanyl-3H-quinazolin-4-one ([(18)F]altanserin) as a useful tool for 5-HT2A receptor PET imaging in vivo (10).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20641567", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 381, "text": "We investigated the relationships of gender, mood, impulsivity, aggression and temperament to 5HT(2A) receptor binding in 21 healthy subjects using [18F]altanserin and PET neuroimaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19959344", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 458, "text": "We, therefore, studied the binding potential of the serotonin 2A (5-HT(2A)) receptor ligand [18F]altanserin in 8 patients with clinically probable PSP and 13 healthy controls using positron emission tomography. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19353726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "[(18)F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19162492", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 448, "text": "Twenty-one healthy subjects underwent PET scanning with the 5-HT(2A) antagonist, [(18)F]altanserin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19007894", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 525, "text": "METHODS: [(18)F]-Altanserin PET was used to quantify 5-HT(2A) receptors in 12 healthy elderly individuals at baseline and at 2 years in six volumes of interest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18828013", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 583, "text": "The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT(2A) receptor (5-HT(2A)R) radioligand [(18)F]altanserin and positron emission tomography (PET)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17541696", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 557, "text": "METHODS: Fifteen women ill with AN (ILL AN) were compared with 29 healthy control women (CW); PET and [11C]WAY100635 were used to assess binding potential (BP) of the 5-HT1A receptor, and [18F]altanserin was used to assess postsynaptic 5-HT2A receptor BP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241616", "endSection": "abstract" }, { "offsetInBeginSection": 2333, "offsetInEndSection": 2634, "text": "In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "[18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15356424", "endSection": "title" }, { "offsetInBeginSection": 653, "offsetInEndSection": 747, "text": "Our data confirmed that [18F]altanserin is a valid tracer for 5HT2 receptors binding studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9257335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10688105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: a film and electronic autoradiographic study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9257335", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "We used [18F]altanserin and positron emission tomography (PET) to image serotonin 5-HT2A receptors in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9027929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Quantification of 5-HT2A receptors in the human brain using [18F]altanserin-PET and the bolus/infusion approach.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12902843", "endSection": "title" }, { "offsetInBeginSection": 2633, "offsetInEndSection": 2744, "text": "These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10587097", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "PURPOSE: To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17195073", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 102, "text": "18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15356424", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Influence of synaptic serotonin level on [18F]altanserin binding to 5HT2 receptors in man.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12642173", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The aim of the present study is to describe and validate a method for accurate quantification of 5-hydroxytryptamine (5-HT)(2A) receptors using [18F]altanserin-positron emission tomography (PET) and the bolus/infusion approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12902843", "endSection": "abstract" }, { "offsetInBeginSection": 1506, "offsetInEndSection": 1819, "text": "The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "endSection": "abstract" }, { "offsetInBeginSection": 2351, "offsetInEndSection": 2651, "text": "In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "endSection": "abstract" }, { "offsetInBeginSection": 2652, "offsetInEndSection": 2762, "text": "These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9824691", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9027929", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Imaging the cerebral serotonin 2A (5-HT2A ) receptors with positron emission tomography (PET) has been carried out in humans with [(11) C]MDL 100907 and [(18) F]altanserin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390031", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 447, "text": "[(18)F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT(2A) receptors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21750562", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 553, "text": "This controlled cross-over PET study aimed to identify brain regions with WM-induced changes in the binding potential (BP(nd)) of the 5-HT2aR antagonist [(18)F]altanserin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21722741", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1346, "text": "MZ and [(18) F]altanserin was blocked by ketanserin supporting that both radioligands bind to 5-HT2A receptors in the pig brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390031", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 680, "text": "PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23456885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10587097", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 535, "text": "To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 752, "text": "Our data confirmed that [18F]altanserin is a valid tracer for 5HT2 receptors binding studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9257335", "endSection": "abstract" }, { "offsetInBeginSection": 2351, "offsetInEndSection": 2650, "text": "In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9826230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10587097", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "We used [18F]altanserin and positron emission tomography (PET) to image serotonin 5-HT2A receptors in humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9027929", "endSection": "abstract" } ] }, { "body": "Which diseases have been associated with the PTPN22 620W allele?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16277672", "http://www.ncbi.nlm.nih.gov/pubmed/16391555", "http://www.ncbi.nlm.nih.gov/pubmed/15790351", "http://www.ncbi.nlm.nih.gov/pubmed/16464986", "http://www.ncbi.nlm.nih.gov/pubmed/22237046", "http://www.ncbi.nlm.nih.gov/pubmed/15719322", "http://www.ncbi.nlm.nih.gov/pubmed/16320352", "http://www.ncbi.nlm.nih.gov/pubmed/19248096", "http://www.ncbi.nlm.nih.gov/pubmed/21752868" ], "ideal_answer": [ "The functional polymorphism 620W in the intracellular tyrosine phosphatase PTPN22 gene has been shown to confer susceptibility to the development of type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, Hashimoto thyroiditis, and Wegener's granulomatosis (granulomatosis with polyangiitis)." ], "exact_answer": [ [ "type 1 diabetes" ], [ "seropositive rheumatoid arthritis" ], [ "systemic lupus erythematosus" ], [ "Hashimoto thyroiditis" ], [ "Wegener's granulomatosis (granulomatosis with polyangiitis)" ] ], "type": "list", "id": "550316a6e9bde69634000029", "snippets": [ { "offsetInBeginSection": 667, "offsetInEndSection": 1045, "text": "The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P\u2009=\u20090.005, \u03c7(2\u2009)=\u20097.858, odds ratio (OR)\u2009=\u20091.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P\u2009=\u20090.00012, \u03c7(2\u2009)=\ufffd\ufffd\ufffd14.73, OR\u2009=\u20092.31)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237046", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1443, "text": "The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22237046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "The PTPN22 620W allele is a risk factor for Wegener's granulomatosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16320352", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 415, "text": "Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16320352", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 948, "text": "The PTPN22 620W allele frequency was significantly increased in antineutrophil cytoplasmic antibody (ANCA)-positive WG patients compared with healthy controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16320352", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1246, "text": "The PTPN22 620W allele appears to be involved in the pathogenesis of WG, and ANCA positivity seems to be the hallmark", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16320352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16277672", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T-cell activation. An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16277672", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 666, "text": "A functional variant (R620W) of the intracellular protein tyrosine phosphatase N22 (PTPN22) has now been conclusively shown to confer approximately two-fold risk for seropositive RA as well as several other autoimmune disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15790351", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 165, "text": "the PTPN22 620W allele associates with multiple autoimmune phenotypes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15719322", "endSection": "title" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1231, "text": "We report that a recently described functional single-nucleotide polymorphism (rs2476601, encoding R620W) in the intracellular tyrosine phosphatase (PTPN22) confers risk of four separate autoimmune phenotypes in these families: T1D, RA, SLE, and Hashimoto thyroiditis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15719322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "The 620W allele of PTPN22 has been associated with susceptibility to several different forms of chronic inflammatory disease, including Type 1 diabetes (T1D), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroiditis (AIT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16391555", "endSection": "abstract" }, { "offsetInBeginSection": 1629, "offsetInEndSection": 1872, "text": "The risk of developing RA later in life in patients with type 1 DM may be attributed, in part, to the presence of the 620W PTPN22 allele, suggesting that this risk factor may represent a common pathway for the pathogenesis of these 2 diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19248096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "The minor allele of the R620W missense single-nucleotide polymorphism (SNP; rs2476601) in the PTPN22 (protein tyrosine phosphatase non-receptor 22) gene has been reported to be associated with multiple autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, autoimmune thyroiditis and vitiligo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16464986", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 356, "text": "An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16277672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "The minor allele of the R620W missense single-nucleotide polymorphism (SNP; rs2476601) in the PTPN22 (protein tyrosine phosphatase non-receptor 22) gene has been reported to be associated with multiple autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, autoimmune thyroiditis and vitiligo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16464986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "The 620W allele of PTPN22 has been associated with susceptibility to several different forms of chronic inflammatory disease, including Type 1 diabetes (T1D), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroiditis (AIT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16391555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "The 620W allele of PTPN22 has been associated with susceptibility to several different forms of chronic inflammatory disease, including Type 1 diabetes (T1D), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroiditis (AIT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16391555", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 963, "text": "PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR)\u2009=\u20092.21, 95% CI 1.4, 3.4, P\u2009<\u20090.0001]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752868", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 357, "text": "An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16277672", "endSection": "abstract" } ] }, { "body": "Which extra thyroid tissues have thyrotropin (TSH) receptors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22517745", "http://www.ncbi.nlm.nih.gov/pubmed/22289392", "http://www.ncbi.nlm.nih.gov/pubmed/22399514", "http://www.ncbi.nlm.nih.gov/pubmed/21956421", "http://www.ncbi.nlm.nih.gov/pubmed/22496347" ], "ideal_answer": [ "TSH receptors are expressed also in extrathyroid tissues. TSH receptors seem to be functional. Extrathyroid tissues include fibrobasts of the orbit and adipose tissue\nThe principal tissues with TSH receptors are:\nadippose tissue\n orbital fibrotic tissue" ], "exact_answer": [ [ "adipose tissue" ], [ "fibrotic tissue" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011989", "http://www.biosemantics.org/jochem#4250044", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004996" ], "type": "list", "id": "513f45abbee46bd34c000013", "snippets": [ { "offsetInBeginSection": 1217, "offsetInEndSection": 1336, "text": "GD orbital fibroblasts, which comprise a mixture of CD34(+) and CD34(-) cells, express much lower levels of Tg and TSHR", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22517745", "endSection": "sections.0" }, { "offsetInBeginSection": 552, "offsetInEndSection": 731, "text": "Previously, we found that CD34(+) progenitor cells, known as fibrocytes, express functional TSHR, infiltrate the orbit, and comprise a large subset of orbital fibroblasts in TAO. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22517745", "endSection": "sections.0" }, { "offsetInBeginSection": 882, "offsetInEndSection": 923, "text": "TSH induced lipolysis in adipose tissues.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496347", "endSection": "sections.0" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1434, "text": "TSH worked as a lipolytic factor in white adipose tissues,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496347", "endSection": "sections.0" }, { "offsetInBeginSection": 303, "offsetInEndSection": 439, "text": "These fibrocytes infiltrate orbital connective tissues in thyroid-associated ophthalmopathy and express functional TSH receptor (TSHR). ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21956421", "endSection": "sections.0" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1104, "text": "TSHR levels are higher than those in orbital fibroblasts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21956421", "endSection": "sections.0" } ] }, { "body": "Which histone modifications distinguish between promoters and enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "http://www.ncbi.nlm.nih.gov/pubmed/21937433", "http://www.ncbi.nlm.nih.gov/pubmed/20008934", "http://www.ncbi.nlm.nih.gov/pubmed/18441229", "http://www.ncbi.nlm.nih.gov/pubmed/19094206", "http://www.ncbi.nlm.nih.gov/pubmed/22421546", "http://www.ncbi.nlm.nih.gov/pubmed/23547170", "http://www.ncbi.nlm.nih.gov/pubmed/12461564", "http://www.ncbi.nlm.nih.gov/pubmed/19295514", "http://www.ncbi.nlm.nih.gov/pubmed/21106759" ], "ideal_answer": [ "H3K27ac is a marker of active enhancers. An enhancer chromatin state signature associated with active developmental enhancers may be defined by high levels of H3K27ac marking, nucleosome displacement, hypersensitivity to sonication, and strong depletion of H3K27me3." ], "exact_answer": [ [ "H3K27ac enrichment" ], [ "H3K27me3 depletion" ] ], "type": "list", "id": "56ddbbaf51531f7e33000009", "snippets": [ { "offsetInBeginSection": 464, "offsetInEndSection": 744, "text": "Here, we used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to measure genome-wide changes in histone H3 acetylation at lysine 27 (H3K27ac), a marker of active enhancers, in unstimulated HUVECs and HUVECs stimulated with VEGFA for 1, 4, and 12 h.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23547170", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 544, "text": "Here we use whole-transcriptome analysis coupled with genome-wide profiling of H3K27ac and H3K27me3 to map chromatin states and enhancers in mouse embryonic forelimb and hindlimb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421546", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 999, "text": "Using H3K27ac profiles, we identified 28,377 putative enhancers, many of which are likely to be limb specific based on strong enrichment near genes highly expressed in the limb and comparisons with tissue-specific EP300 sites and known enhancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421546", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1219, "text": "a chromatin state signature associated with active developmental enhancers, defined by high levels of H3K27ac marking, nucleosome displacement, hypersensitivity to sonication, and strong depletion of H3K27me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421546", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1434, "text": "We also find that some developmental enhancers exhibit components of this signature, including hypersensitivity, H3K27ac enrichment, and H3K27me3 depletion, at lower levels in tissues in which they are not active.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22421546", "endSection": "abstract" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1472, "text": "At some locations, H3K27 monomethylation was also found to be associated with chromatin signatures of gene enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21937433", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 413, "text": "Individual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 843, "text": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 413, "text": "Although certain chromatin features, such as the histone acetyltransferase P300 and the histone modification H3K4me1, indicate the presence of enhancers, only a fraction of enhancers are functionally active. Individual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 843, "text": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "abstract" } ] }, { "body": "Where is the metaxin complex localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19552401", "http://www.ncbi.nlm.nih.gov/pubmed/11027586", "http://www.ncbi.nlm.nih.gov/pubmed/17981999", "http://www.ncbi.nlm.nih.gov/pubmed/17624330", "http://www.ncbi.nlm.nih.gov/pubmed/10381257", "http://www.ncbi.nlm.nih.gov/pubmed/9045676", "http://www.ncbi.nlm.nih.gov/pubmed/9705320", "http://www.ncbi.nlm.nih.gov/pubmed/17510655" ], "ideal_answer": [ "The metaxin complex is localized to the outer mitochondrial membrane." ], "exact_answer": [ "To the outer mitochondrial membrane." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032991", "http://www.uniprot.org/uniprot/MTX1_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043234" ], "type": "factoid", "id": "54e0ba781388e8454a000011", "snippets": [ { "offsetInBeginSection": 1554, "offsetInEndSection": 1797, "text": " The C-terminus plays an important role in targeting TSPO to mitochondria, whereas its import into the OMM is dependent upon the presence of the Schellman motif. Final integration of TSPO into the OMM occurs via its interaction with Metaxin 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19552401", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 443, "text": " TOM20 (translocase of the outer mitochondrial membrane), METAXIN, and mtOM64 (outer mitochondrial membrane protein of 64 kD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17981999", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1068, "text": "The outer membrane protein METAXIN was characterized to play a role in the import of mitochondrial precursor proteins and likely plays a role in the assembly of beta-barrel proteins into the outer membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17981999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17624330", "endSection": "title" }, { "offsetInBeginSection": 440, "offsetInEndSection": 838, "text": " The functional role of this new complex is uncertain. However, a role in protein import related to maintenance of mitochondrial structure is suggested as mitofilin helps regulate mitochondrial morphology and at least four of the associated proteins (metaxins 1 and 2, SAM50 and CHCHD3) have been implicated in protein import, while DnaJC11 is a chaperone-like protein that may have a similar role.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17624330", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1253, "text": "We conclude that the pathway of VDAC biogenesis in human mitochondria involves the TOM complex, Sam50 and metaxins, and that it is evolutionarily conserved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17510655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Functional analysis of human metaxin in mitochondrial protein import in cultured cells and its relationship with the Tom complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11027586", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Metaxin is an outer membrane protein of mammalian mitochondria which is suggested to be involved in protein import into the organelle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11027586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Metaxin 1 interacts with metaxin 2, a novel related protein associated with the mammalian mitochondrial outer membrane.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10381257", "endSection": "title" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1021, "text": "In subcellular fractions of mouse liver, a 29 kD immunoreactive protein, consistent in size with the predicted translation product of metaxin 2 cDNA, was found solely in mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10381257", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1313, "text": ". Metaxin 2 in intact mitochondria was susceptible to digestion with proteinase K, indicating that metaxin 2 is located on the cytosolic face of the mitochondrial outer membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10381257", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 285, "text": "metaxin gene (Mtx), which encodes an outer mitochondrial membrane import protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9705320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Metaxin is a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9045676", "endSection": "title" } ] }, { "body": "What are the major classes of retrotransposons active in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22528351", "http://www.ncbi.nlm.nih.gov/pubmed/23282240", "http://www.ncbi.nlm.nih.gov/pubmed/15867427", "http://www.ncbi.nlm.nih.gov/pubmed/22923465", "http://www.ncbi.nlm.nih.gov/pubmed/2165587", "http://www.ncbi.nlm.nih.gov/pubmed/16511833", "http://www.ncbi.nlm.nih.gov/pubmed/10677855", "http://www.ncbi.nlm.nih.gov/pubmed/16399224", "http://www.ncbi.nlm.nih.gov/pubmed/12213770", "http://www.ncbi.nlm.nih.gov/pubmed/11343131", "http://www.ncbi.nlm.nih.gov/pubmed/12167372", "http://www.ncbi.nlm.nih.gov/pubmed/22093876", "http://www.ncbi.nlm.nih.gov/pubmed/17431169" ], "ideal_answer": [ "LINE-1 (L1), Alu, SVA" ], "exact_answer": [ [ "LINE-1", "L1" ], [ "Alu" ], [ "SVA" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018626" ], "type": "list", "id": "517843638ed59a060a000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Half of the human genome is composed of repeated DNA, and some types are mobile within our genome (transposons and retrotransposons). Despite their abundance, only a small fraction of them are currently active in our genome (Long Interspersed Element-1 (LINE-1), Alu, and SVA elements).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22528351", "endSection": "sections.0" }, { "offsetInBeginSection": 114, "offsetInEndSection": 343, "text": "Since certain types of retrotransposons, particularly members of the Alu, L1, and SVA families, are still active, their recent and ongoing propagation generates a unique and important class of human genomic diversity/polymorphism", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16511833", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Alu elements are the most successful SINEs (Short INterspersed Elements) in primate genomes and have reached more than 1,000,000 copies in the human genome", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15867427", "endSection": "sections.0" }, { "offsetInBeginSection": 120, "offsetInEndSection": 201, "text": "1 and Alu represent the most prolific human LINE and SINE families, respectively.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12213770", "endSection": "sections.0" }, { "offsetInBeginSection": 202, "offsetInEndSection": 328, "text": "Only a few Alu elements are able to retropose, and the factors determining their retroposition capacity are poorly understood.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12213770", "endSection": "sections.0" } ] }, { "body": "Which are the clinical characteristics of Diamond-Blackfan anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22739174", "http://www.ncbi.nlm.nih.gov/pubmed/12679976", "http://www.ncbi.nlm.nih.gov/pubmed/20960466", "http://www.ncbi.nlm.nih.gov/pubmed/23795277", "http://www.ncbi.nlm.nih.gov/pubmed/20603584", "http://www.ncbi.nlm.nih.gov/pubmed/24662257", "http://www.ncbi.nlm.nih.gov/pubmed/16239073" ], "ideal_answer": [ "Diamond-Blackfan anemia (DBA) is a rare congenital erythroid hypoplastic anemia that usually presents early in infancy and is characterized by red cell aplasia, congenital anomalies, and a predisposition to cancer." ], "exact_answer": [ [ "Red cell aplasia" ], [ "Congenital anomalies" ], [ "Predisposition to cancer" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029503", "http://www.disease-ontology.org/api/metadata/DOID:1339" ], "type": "list", "id": "55031286e9bde6963400001b", "snippets": [ { "offsetInBeginSection": 331, "offsetInEndSection": 686, "text": "The results indicated that out of 45 children diagnosed as DBA, 14 cases (31.1%) had short stature and physical malformation. All patients had anemia with reticulocytopenia. Thirty-four patients (75.6%) had mean corpuscular volume. Eleven patients (24.4%) had macrocytic anemia. Bone marrow examination showed a marked erythroid hypoplasia in all patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22739174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Diamond-Blackfan anemia (DBA) is a rare congenital erythroid hypoplastic anemia that usually presents early in infancy and is inherited in up to 45% of cases. It is characterized by red cell aplasia, congenital anomalies, and a predisposition to cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20603584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Diamond-Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20960466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Diamond Blackfan Anemia (DBA) is a rare hypoplastic anemia that presents in infancy with macrocytic anemia and reticulocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23795277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Diamond Blackfan anemia is characterized by a severe hypoplastic anemia and a heterogeneous collection of other clinical features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Diamond-Blackfan anaemia (congenital hypoplastic anaemia) is a rare hereditary disease with isolated congenital hypoplasia of red blood cells precursors in bone marrow, and its important characteristic is successful treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12679976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Diamond-Blackfan anemia is a rare, inherited disease that characteristically presents as a chronic, normochromic macrocytosis due to red cell lineage bone marrow failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24662257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Diamond Blackfan anemia is characterized by a severe hypoplastic anemia and a heterogeneous collection of other clinical features", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239073", "endSection": "abstract" } ] }, { "body": "How can the expression of SerH3 immobilization antigen be regulated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2854007", "http://www.ncbi.nlm.nih.gov/pubmed/3537733", "http://www.ncbi.nlm.nih.gov/pubmed/3915784", "http://www.ncbi.nlm.nih.gov/pubmed/7828814", "http://www.ncbi.nlm.nih.gov/pubmed/4054606", "http://www.ncbi.nlm.nih.gov/pubmed/2233735", "http://www.ncbi.nlm.nih.gov/pubmed/8414992", "http://www.ncbi.nlm.nih.gov/pubmed/11973302", "http://www.ncbi.nlm.nih.gov/pubmed/3211135", "http://www.ncbi.nlm.nih.gov/pubmed/1522546", "http://www.ncbi.nlm.nih.gov/pubmed/3336362", "http://www.ncbi.nlm.nih.gov/pubmed/7731807" ], "triples": [ { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q9U697", "o": "http://linkedlifedata.com/resource/#_513955363937005" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513955363937005", "o": "SerH3 immobilization antigen" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q22YJ5", "o": "http://linkedlifedata.com/resource/#_513232594A35007" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513232594A35007", "o": "SerH3 immobilization antigen, putative" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q23VE7", "o": "http://linkedlifedata.com/resource/#_513233564537007" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513233564537007", "o": "SerH3 immobilization antigen, putative" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q22TF4", "o": "http://linkedlifedata.com/resource/#_513232544634007" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513232544634007", "o": "SerH3 immobilization antigen, putative" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q9U697", "o": "http://linkedlifedata.com/resource/#_513955363937008" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513955363937008", "o": "SerH3" } ], "ideal_answer": [ "The expression of Tetrahymena surface proteins serotype H3 (SerH3) is under temperature regulation. SerH3 is expressed when cells are incubated between the temperatures of 20 and 35 degrees C." ], "exact_answer": [ "Temperature regulation" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005786", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012703", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010628", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010629", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010468", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007103", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000941" ], "type": "factoid", "id": "5335f053d6d3ac6a34000055", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "mRNA stability plays a major role in regulating the temperature-specific expression of a Tetrahymena thermophila surface protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3336362", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The presence of specific proteins (known as immobilization antigens) on the surface of the ciliated protozoan Tetrahymena thermophila is under environmental regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3537733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "A temperature shift from 40 to 28 degrees C rapidly induced expression of a specific immobilization antigen at the cell surface in Tetrahymena thermophila. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3915784", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1163, "text": "Expression of each allele is regulated by temperature-sensitive mRNA stability. H mRNAs are stable at <36 degrees but are unstable at >36 degrees. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11973302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "In Tetrahymena thermophila, the expression of the temperature-specific surface protein SerH3 is controlled primarily by a temperature-dependent change in the stability of its mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7731807", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 450, "text": "we studied SerH3-ts1, a temperature-sensitive allele of the temperature-regulated SerH3 gene normally expressed from 20-36 degrees. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7828814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "In Tetrahymena thermophila, the expression of a temperature-specific surface protein known as SerH3 is primarily controlled by a temperature-dependent change in the stability of the mRNA that encodes this protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8414992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "The expression of Tetrahymena surface proteins serotype H3 (SerH3) and serotype T (SerT) is under environmental regulation. SerH3 is expressed when cells are incubated between the temperatures of 20 and 35 degrees C, while SerT is expressed when cells are grown at temperatures above 35 degrees C. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3211135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The surfaces of Tetrahymena thermophila cells grown between 20 and 35 degrees C are covered by one or more variants of H antigens. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2854007", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 117, "text": "SerH3, a Tetrahymena thermophila gene encoding a temperature-regulated surface antigen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2233735", "endSection": "title" }, { "offsetInBeginSection": 274, "offsetInEndSection": 473, "text": "In the holotrich Tetrahymena thermophila five alternative cell surface immobilization proteins (i-antigens) are expressed under different conditions of temperature (L, H, T) and culture media (I, S).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1522546", "endSection": "abstract" } ] }, { "body": "Which factors play a role in promoter proximal pausing of RNA polymerase II?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23589332", "http://www.ncbi.nlm.nih.gov/pubmed/19245807", "http://www.ncbi.nlm.nih.gov/pubmed/18373978", "http://www.ncbi.nlm.nih.gov/pubmed/12782658", "http://www.ncbi.nlm.nih.gov/pubmed/20534440", "http://www.ncbi.nlm.nih.gov/pubmed/17942706", "http://www.ncbi.nlm.nih.gov/pubmed/24050178", "http://www.ncbi.nlm.nih.gov/pubmed/22244331", "http://www.ncbi.nlm.nih.gov/pubmed/22549956", "http://www.ncbi.nlm.nih.gov/pubmed/17567605", "http://www.ncbi.nlm.nih.gov/pubmed/23699410", "http://www.ncbi.nlm.nih.gov/pubmed/16880520", "http://www.ncbi.nlm.nih.gov/pubmed/19860741", "http://www.ncbi.nlm.nih.gov/pubmed/20028984", "http://www.ncbi.nlm.nih.gov/pubmed/21670248", "http://www.ncbi.nlm.nih.gov/pubmed/18332113", "http://www.ncbi.nlm.nih.gov/pubmed/20170405" ], "ideal_answer": [ "NELF (negative elongator factor) and DSIF (DRB Sensitivity Inducing Factor)" ], "exact_answer": [ [ "NELF" ], [ "DSIF" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006366", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012319" ], "type": "list", "id": "533ec7abc45e133714000015", "snippets": [ { "offsetInBeginSection": 589, "offsetInEndSection": 720, "text": "Among the factors we describe are the pausing factors--NELF (negative elongation factor) and DSIF (DRB sensitivity-inducing factor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24050178", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1023, "text": "BMP target gene expression requires the pause-inducing negative elongation factor (NELF) complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23699410", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 151, "text": "NA polymerase II (Pol II) and the pausing complex, NELF and DSIF, are detected near the transcription start site (TSS) of many active and silent genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23589332", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 93, "text": "pausing complex NELF/DSIF", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23589332", "endSection": "title" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1013, "text": "knockdown of the pause-inducing factor NELF leads to broadly attenuated immune gene activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22549956", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 493, "text": "pausing factors NELF and DSIF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22244331", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 839, "text": "pausing factors NELF and DSIF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21670248", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 761, "text": "pausing factor DSIF (DRB sensitivity-inducing factor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942706", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 204, "text": "(NELF) and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF) are involved in pausing RNA Polymerase II (Pol II) in the promoter-proximal region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20534440", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 562, "text": "Pausing and resumption of the elongation of transcripts is under the control of transcription elongation factors. Three of them, P-TEFb, DSIF, and NELF have been well characterized ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20170405", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 207, "text": "NELF-mediated stalling of RNAPII ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20028984", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 525, "text": "At several eukaryotic promoters, DSIF, together with NELF (negative elongation factor), leads to promoter-proximal pausing of RNA polymerase II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19860741", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 70, "text": "negative transcription elongation factor NELF", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19245807", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 366, "text": "(DSIF), is involved in regulating the processivity of RNA polymerase II. DSIF plays also a role in transcriptional activation, and in concert with the negative elongation factor NELF causes promoter proximal pausing of RNA polymerase II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18373978", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 194, "text": "NELF causes Pol II to pause in the promoter-proximal region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18332113", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 275, "text": "(DSIF) regulates RNA polymerase II (RNAPII) processivity by promoting, in concert with negative elongation factor (NELF), promoter-proximal pausing of RNAPI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17567605", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 212, "text": "(DSIF) and negative elongation factor (NELF) negatively regulate transcription elongation by RNA polymerase II (RNAPII) in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16880520", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 39, "text": "pausing caused by NELF ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16880520", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 69, "text": "ELF and DSIF collaborate to inhibit elongation by RNA polymerase IIa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12782658", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 720, "text": "The presence of DSIF reduced pausing,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17567605", "endSection": "abstract" } ] }, { "body": "Which are the main clinical features of Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12525534", "http://www.ncbi.nlm.nih.gov/pubmed/8058745", "http://www.ncbi.nlm.nih.gov/pubmed/23444773", "http://www.ncbi.nlm.nih.gov/pubmed/21956823", "http://www.ncbi.nlm.nih.gov/pubmed/24773018", "http://www.ncbi.nlm.nih.gov/pubmed/23585528", "http://www.ncbi.nlm.nih.gov/pubmed/21131752", "http://www.ncbi.nlm.nih.gov/pubmed/9389754", "http://www.ncbi.nlm.nih.gov/pubmed/10915769", "http://www.ncbi.nlm.nih.gov/pubmed/24604962", "http://www.ncbi.nlm.nih.gov/pubmed/16675878" ], "ideal_answer": [ "Fanconi anaemia (FA) is an autosomal recessive disease characterised by congenital abnormalities, defective haemopoiesis, and increased risk of malignancies.", "Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors" ], "exact_answer": [ [ "congenital abnormalities" ], [ "defective haemopoiesis" ], [ "increased risk of malignancies" ], [ "cellular hypersensitivity to DNA crosslinking agents" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062", "http://www.disease-ontology.org/api/metadata/DOID:13636" ], "type": "list", "id": "54ecb640445c3b5a5f000001", "snippets": [ { "offsetInBeginSection": 160, "offsetInEndSection": 337, "text": "The clinical features of cytopenia, developmental defects, and tumor predisposition are similar in each group, suggesting that the gene products participate in a common pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24773018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24604962", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 401, "text": "Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21956823", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 261, "text": "Fanconi anemia (FA) is an autosomal recessive, cancer susceptibility disorder characterized by diverse clinical features, such as short stature, skeletal or skin abnormalities, progressive bone marrow (BM) failure, and increased risk of malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21131752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Fanconi anaemia (FA) is an autosomal recessive disease characterised by congenital abnormalities, defective haemopoiesis, and a high risk of developing acute myeloid leukaemia and certain solid tumours", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12525534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Fanconi anemia (FA), a recessive syndrome with both autosomal and X-linked inheritance, features diverse clinical symptoms, such as progressive bone marrow failure, hypersensitivity to DNA cross-linking agents, chromosomal instability and susceptibility to cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Fanconi anemia (FA) consists of a group of at least five autosomal recessive disorders that share both clinical (e.g., birth defects and hematopoietic failure) and cellular (e.g., sensitivity to cross-linking agents and predisposition to apoptosis) features with each other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9389754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8058745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Progressive bone marrow failure starting in the first decade of life is one of the main characteristics of Fanconi anemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23585528", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 506, "text": "FA is an autosomal recessive disease with three main features: chromosome instability, hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), cisplatin and so on, and susceptible to a number of cancer types, mainly leukemia and squamous cell carcinomas of the head and neck or gynecologic system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444773", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 184, "text": "Bone marrow failure resulting in pancytopenia is the main cause of death of FA patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10915769", "endSection": "abstract" } ] }, { "body": "Which is the receptor for the immunosuppressive drug cyclosporin A (CsA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25707381", "http://www.ncbi.nlm.nih.gov/pubmed/2477715", "http://www.ncbi.nlm.nih.gov/pubmed/3043797" ], "ideal_answer": [ "Cyclophilin is the intracellular receptor protein for cyclosporin A (CsA)." ], "exact_answer": [ "cyclophilin" ], "type": "factoid", "id": "56f6c11109dd18d46b00000e", "snippets": [ { "offsetInBeginSection": 220, "offsetInEndSection": 360, "text": "hemical modification of CsA has led to analogs with distinct biological activities associated with its protein receptor family, cyclophilins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25707381", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 579, "text": " the CsA receptor, cyclophilin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2477715", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1271, "text": "These results would support cyclophilin as the major, if not only, intracellular receptor protein for CsA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3043797", "endSection": "abstract" } ] }, { "body": "Which drugs may interfere thyroxine absorption?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23264396", "http://www.ncbi.nlm.nih.gov/pubmed/21595516", "http://www.ncbi.nlm.nih.gov/pubmed/18996189", "http://www.ncbi.nlm.nih.gov/pubmed/18845642", "http://www.ncbi.nlm.nih.gov/pubmed/16898074", "http://www.ncbi.nlm.nih.gov/pubmed/17711927", "http://www.ncbi.nlm.nih.gov/pubmed/12796075", "http://www.ncbi.nlm.nih.gov/pubmed/17446037", "http://www.ncbi.nlm.nih.gov/pubmed/21516059", "http://www.ncbi.nlm.nih.gov/pubmed/19733399", "http://www.ncbi.nlm.nih.gov/pubmed/18466075", "http://www.ncbi.nlm.nih.gov/pubmed/15142360", "http://www.ncbi.nlm.nih.gov/pubmed/22908106", "http://www.ncbi.nlm.nih.gov/pubmed/19942153", "http://www.ncbi.nlm.nih.gov/pubmed/17725434", "http://www.ncbi.nlm.nih.gov/pubmed/19226259", "http://www.ncbi.nlm.nih.gov/pubmed/19789374", 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"http://www.ncbi.nlm.nih.gov/pubmed/22099156", "http://www.ncbi.nlm.nih.gov/pubmed/15301044" ], "ideal_answer": [ "bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine\nsevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours" ], "exact_answer": [ [ "bile acide sequestrant" ], [ "ferrous sulphate" ], [ "sucralfate" ], [ "Calcium carbonate" ], [ "aluminium-containing antacids" ], [ "raloxifene" ], [ "proton pump inhibithors" ], [ "sevelamer" ], [ "chromium picolinate" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4250045", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000042" ], "type": "list", "id": "513f3d1fbee46bd34c000010", "snippets": [ { "offsetInBeginSection": 319, "offsetInEndSection": 579, "text": "ommonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19942153", "endSection": "sections.0" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1272, "text": "Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17725434", "endSection": "sections.0" } ] }, 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Turcot syndrome is an autosomal recessive disorder clinically characterized by the occurrence of primary glial tumors of the central nervous system, including glioblastoma, and adenomatous colonic polyps during the first or second decades of life, with a spectrum of clinical features such as \"caf\u00e9-au-lait\" spots, axillary freckling, and hyperpigmented spots." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3073", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005909" ], "type": "yesno", "id": "533581f5d6d3ac6a3400004d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "Turcot syndrome is an autosomal recessive disorder clinically characterized by the occurrence of primary tumors of the central nervous system and adenomatous colonic polyps during the first or second decades of life, with a spectrum of clinical features such as \"caf\u00e9-au-lait\" spots, axillary freckling, and hyperpigmented spots. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23320220", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 541, "text": "We present the case of a 20-year-old male with a clinical presentation of both glioblastoma multiforme and multiple adenomatous colonic polyps. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23320220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Turcot syndrome (TS) is a rare hereditary disorder clinically characterized by the occurrence of primary tumors of the colon and the central nervous system (CNS). Here we present the case of an 11-year-old boy with a synchronous clinical presentation of both glioblastoma multiforme (GBM) and colonic adenocarcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23119205", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 681, "text": "Based on this case study, the synchronous presentation of glioblastoma multiforme and adenocarcinoma of the colon might suggest a shorter survival rate for patients with Turcot syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23119205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 526, "text": "A 15-year-old boy was admitted with the diagnosis of colonic polyposis, and during a 2-year follow-up, he underwent operation for right parieto-occipital anaplastic astrocytoma, left-side colonic non-Hodgkin lymphoma (NHL) and cerebella glioblastoma which were all confirmed by histology. Although cases of Turcot's syndrome (TS) (colonic polyposis and primary brain tumour occurring in the same patient) have been previously described, association with haematological malignancy is rare. We hereby report such a case with TS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22676959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156169", "endSection": "title" }, { "offsetInBeginSection": 567, "offsetInEndSection": 696, "text": " Biallelic mutations of MMR genes are associated with pediatric cancers, including glial tumors, in Turcot syndrome type 1 (TS1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Glioblastomas with giant cell and sarcomatous features in patients with Turcot syndrome type 1: a clinicopathological study of 3 cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20657316", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "Turcot syndrome (TS) is a rare genetic disorder of DNA mismatch repair predisposing to glioblastoma (GBM) in the type 1 variant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20657316", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 242, "text": "We report the clinicopathological and genetic features of 3 gliomas in TS type 1 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20657316", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1739, "text": "We conclude that 1) the giant cell variant of GBM is overrepresented in TS; 2) gliosarcomas may also be encountered; and 3) survival is often favorable, despite histological anaplasia and exuberant proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20657316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17138070", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "A 45-year-old woman with anaplastic astrocytoma was clinically diagnosed with Turcot syndrome, and subsequently developed simultaneous neurocysticercosis and malignant transformation to glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17138070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Familial glioblastoma multiforme is a rather uncommon entity, being in most cases associated to known genetic disorders (as Turcot syndrome, Li-Fraumeni syndrome, neurofibromatosis, etc.). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16960645", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 331, "text": "Turcot syndrome (MIM276300) has been described as the association of central nervous system malignant tumors and familial colorectal cancer and has been reported to be both a dominant and recessive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16000562", "endSection": "abstract" }, { "offsetInBeginSection": 1380, "offsetInEndSection": 1568, "text": "We report here the first identification of a homozygous mutation in MSH6 in a family with childhood-onset brain tumor, lymphoma, colorectal cancer, and neurofibromatosis type 1 phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16000562", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1388, "text": "Of the 21 patients, 12 have died (10 after relapse, with a median time to progression for the whole series of 14 months; one with intratumoral bleeding at 40 months after diagnosis; and one affected by Turcot syndrome for duodenal cancer relapse).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "[Glioblastoma multiforme as a manifestation of Turcot syndrome].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11975096", "endSection": "title" }, { "offsetInBeginSection": 273, "offsetInEndSection": 451, "text": "In the present case, a 60-year-old patient with glioblastoma multiforme and a history of hereditary malignomas is described as an example of a HNPCC-associated Turcot's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11975096", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 426, "text": "Computed tomography brain scan and computed tomography-guided biopsy revealed a left frontoparietal glioblastoma multiforme. This case illustrates the rare presentation of Turcot syndrome-a hereditary colorectal polyposis syndrome-in an older adult.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11907360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Turcot syndrome is the association of colorectal polyposis with primary neuroepithelial tumors of the central nervous system such as glioblastoma and medulloblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10921328", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 879, "text": "Brain tumor is mainly diagnosed as glioblastoma or astrocytoma and mismatch repair genes might be involved. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10921328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10223463", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 831, "text": "Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10223463", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 407, "text": "Turcot Syndrome caused by APC gene develops medulloblastoma and Turcot Syndrome caused by mismatch repair gene develops glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9695069", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 271, "text": "It is characterized by central nervous system (CNS) neoplasms and gastrointestinal polyposis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9508118", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 563, "text": "Seven months after resection of this Dukes' C2 adenocarcinoma, she presented with a second primary CNS tumor, a glioblastoma multiforme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9508118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The Turcot syndrome has been defined as the simultaneous presence of multiple polyposis of the colon and a malignant brain tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9505220", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 485, "text": "The case of a 47-year-old man submitted to a right hemicolectomy for cancer and polyposis, following a series of endoscopic polypectomies and, finally, removal of left temporal glioma is here presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9505220", "endSection": "abstract" }, { "offsetInBeginSection": 2254, "offsetInEndSection": 2381, "text": " Two of 13 showed microsatellite instability, one of which in a patient with Turcot syndrome, the other in gliomatosis cerebri.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9343324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "The Turcot syndrome (TS) is a rare, probably autosomal recessive, disorder characterized by development of primary neuroepithelial tumors of the central nervous system (CNS) and numerous adenomatous colorectal polyps. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7515658", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 857, "text": "However, no somatic mutations in APC were found among 91 neuroepithelial tumors (medulloblastoma, glioblastoma, astrocytoma, and oligodendroglioma), whether sporadic or associated with TS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7515658", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 378, "text": "Such syndromes include neurofibromatosis type 2, neurofibromatosis type 1, Li-Fraumeni syndrome, as well as von Hippel-Lindau disease, tuberous sclerosis, and Turcot syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8025896", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 242, "text": "This patient's case deals with the association between a glioblastoma, anaplastic glioma (WHO Grade III) and colonic adenocarcinoma based on familial polyposis coli. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8127448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The authors describe two patients with the association of polyposis-coli and central nervous system tumor (Turcot's syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2165772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "We report a case of Turcot's syndrome in a 20-year old man with multiple adenomatous polyps of the colon and glioblastoma multiforme. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2540108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Another unusual autopsy case of the Turcot syndrome is reported in a 23-year-old woman with polyposis coli, who developed primary carcinoma of the jejunum and glioblastoma multiforme of the left frontal lobe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6307612", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 291, "text": "Turcot syndrome represents the unique and discrete occurrence of polyposis coli with glioblastoma multiforme, medulloblastoma, or both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6274254", "endSection": "abstract" } ] }, { "body": "Which is the gene most commonly mutated in Tay-Sachs disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2967444", "http://www.ncbi.nlm.nih.gov/pubmed/14648242", "http://www.ncbi.nlm.nih.gov/pubmed/8411703", "http://www.ncbi.nlm.nih.gov/pubmed/3362213", "http://www.ncbi.nlm.nih.gov/pubmed/22441121", "http://www.ncbi.nlm.nih.gov/pubmed/20363167", "http://www.ncbi.nlm.nih.gov/pubmed/7858168", "http://www.ncbi.nlm.nih.gov/pubmed/8490625", "http://www.ncbi.nlm.nih.gov/pubmed/3375249", "http://www.ncbi.nlm.nih.gov/pubmed/9401008", "http://www.ncbi.nlm.nih.gov/pubmed/22723944" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4016", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/HEXA" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/HEXA", "o": "HEXA" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/HEXA", "o": "http://www.dbpedia.org/resource/HEXA" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4016", "o": "Tay-Sachs disease, 272800" } ], "ideal_answer": [ "HEXA gene, encoding the alpha-subunit of the lysosomal enzyme, beta-N-acetylhexosaminidase A" ], "exact_answer": [ "HEXA" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049290", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005678", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013661", "http://www.disease-ontology.org/api/metadata/DOID:3320" ], "type": "factoid", "id": "536e46f27d100faa09000012", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 81, "text": "mutations in the HEXA gene among Iraqi Jewish Tay-Sachs disease carriers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14648242", "endSection": "title" }, { "offsetInBeginSection": 4, "offsetInEndSection": 81, "text": "mutated HEXA alleles in a Druze patient with late-infantile Tay-Sachs disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401008", "endSection": "title" }, { "offsetInBeginSection": 4, "offsetInEndSection": 101, "text": "affected HEXA alleles were found in an Israeli Druze Tay-Sachs child born to first-cousin parents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401008", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 141, "text": "abnormalities in the gene coding for the beta-hexosaminidase alpha subunit were analysed from fibroblast's RNAs of 42 Tay-Sachs patients ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7858168", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 804, "text": "In the severest phenotype of Tay-Sachs disease (infantile form), mRNA of beta-hexosaminidase alpha subunit is not produced or is unstable", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8411703", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 69, "text": "novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8490625", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 140, "text": "ay-Sachs disease is an inherited disorder in which the alpha chain of the lysosomal enzyme beta-N-acetylhexosaminidase A bears the mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3375249", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 183, "text": "ay-Sachs disease is an autosomal recessive genetic disorder resulting from mutation of the HEXA gene encoding the alpha-subunit of the lysosomal enzyme, beta-N-acetylhexosaminidase A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3362213", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 370, "text": "Tay-Sachs disease lack detectable alpha-chain message when analyzed by Northern blotting with complementary DNA encoding the alpha-chain of human beta-hexosaminidase A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2967444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Identification of novel mutations in HEXA gene in children affected with Tay Sachs disease from India.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723944", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Molecular analysis of HEXA gene in Argentinean patients affected with Tay-Sachs disease: possible common origin of the prevalent c.459+5A>G mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22441121", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Tay-Sachs disease (TSD) is a recessively inherited disorder caused by the deficient activity of hexosaminidase A due to mutations in the HEXA gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22441121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Specific mutations in the HEXA gene among Iraqi Jewish Tay-Sachs disease carriers: dating of founder ancestor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14648242", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Two mutated HEXA alleles in a Druze patient with late-infantile Tay-Sachs disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401008", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "We have identified three mutations in the beta-hexoseaminidase A (HEXA) gene in a juvenile Tay-Sachs disease (TSD) patient, which exhibited a reduced level of HEXA mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20363167", "endSection": "abstract" } ] }, { "body": "In which types of DNA repair is the UvrAB complex involved?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10913608", "http://www.ncbi.nlm.nih.gov/pubmed/8702928", "http://www.ncbi.nlm.nih.gov/pubmed/9049316", "http://www.ncbi.nlm.nih.gov/pubmed/17630776", "http://www.ncbi.nlm.nih.gov/pubmed/2665605", "http://www.ncbi.nlm.nih.gov/pubmed/12145219", "http://www.ncbi.nlm.nih.gov/pubmed/10811888", "http://www.ncbi.nlm.nih.gov/pubmed/8969181", "http://www.ncbi.nlm.nih.gov/pubmed/11101153", "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "http://www.ncbi.nlm.nih.gov/pubmed/11551204", "http://www.ncbi.nlm.nih.gov/pubmed/9049317", "http://www.ncbi.nlm.nih.gov/pubmed/20227373" ], "ideal_answer": [ "UvrB and the lesion-recognition factor UvrA form the UvrAB complex, which plays a key role in bacterial nucleotide excision repair (NER). In transcription-coupled repair (TCR), the transcription repair coupling factor Mfd recruits uvrA, and the assembled UvrAB complex initiates repair. UvrAB complex also suppresses illegitimate recombination." ], "exact_answer": [ [ "nucleotide excision repair (NER)" ], [ "transcription-coupled repair (TCR)" ], [ "suppression of illegitimate recombination" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006281", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260" ], "type": "list", "id": "553f7a71ab98a37113000009", "snippets": [ { "offsetInBeginSection": 763, "offsetInEndSection": 828, "text": "illegitimate recombination is mostly suppressed by UvrA and UvrB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10811888", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1191, "text": "UvrAB complex suppresses illegitimate recombination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10811888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Transcription-coupled repair (TCR) is a subpathway of nucleotide excision repair (NER) that acts specifically on lesions in the transcribed strand of expressed genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 531, "text": "the transcription repair coupling factor, Mfd. This protein recruits the NER lesion-recognition factor UvrA, and then dissociates from the DNA. UvrA binds UvrB, and the assembled UvrAB* complex initiates repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "UvrB plays a key role in bacterial nucleotide excision repair. It is the ultimate damage-binding protein that interacts with both UvrA and UvrC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17630776", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 478, "text": "UvrB subunits bind to UvrA, most likely as part of a UvrA2B2 complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17630776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Escherichia coli nucleotide excision repair (NER) is responsible for removing bulky DNA adducts by dual incisions of the UvrABC endonuclease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10913608", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 246, "text": "the activity of the UvrAB complex which can induce DNA conformational change is employed in NER", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10913608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 450, "text": "The recognition by Escherichia coli Uvr nucleotide excision repair proteins of a variety of lesions with diverse chemical structures and the presence of helicase activity in the UvrAB complex which can displace short oligonucleotides annealed to single-stranded DNA led to a model in which this activity moves UvrAB along undamaged DNA to damaged sites where the lesion blocks further translocation and the protein-DNA pre-incision complex is formed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9049317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Transcription when coupled to nucleotide excision repair specifies the location in active genes where preferential DNA repair is to take place.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8702928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Transcription when coupled to nucleotide excision repair specifies the location in active genes where preferential DNA repair is to take place", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8702928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "The recognition by Escherichia coli Uvr nucleotide excision repair proteins of a variety of lesions with diverse chemical structures and the presence of helicase activity in the UvrAB complex which can displace short oligonucleotides annealed to single-stranded DNA led to a model in which this activity moves UvrAB along undamaged DNA to damaged sites where the lesion blocks further translocation and the protein-DNA pre-incision complex is formed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9049317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Transcription-coupled DNA repair in prokaryotes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "endSection": "title" } ] }, { "body": "What is the localization of the protein encoded by the gene DNAJC11?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17624330" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11657583", "o": "25570" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1539296", "o": "http://linkedlifedata.com/resource/umls/label/A11695815" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17746647", "o": "DNAJC11" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11695815", "o": "DnaJ 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"http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12988852", "o": "DNAJC11 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1453469", "o": "http://linkedlifedata.com/resource/umls/label/A12996051" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12988853", "o": "C487553" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12996051", "o": "C487553" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12988852", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12988853", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12996051", "o": "MeSH" } ], "ideal_answer": [ "mitochondrial inner membrane" ], "exact_answer": [ "mitochondrial inner membrane" ], "concepts": [ "http://www.uniprot.org/uniprot/DJC11_PONAB", "http://www.uniprot.org/uniprot/DJC11_DICDI", "http://www.uniprot.org/uniprot/DJC11_HUMAN", "http://www.uniprot.org/uniprot/DJC11_MOUSE", "http://www.uniprot.org/uniprot/DJC11_BOVIN" ], "type": "factoid", "id": "531e2695267d7dd05300000f", "snippets": [ { "offsetInBeginSection": 247, "offsetInEndSection": 440, "text": " DnaJC11, respectively. The first three are outer membrane proteins, CHCHD3 has been assigned to the matrix space, and the other two proteins have not been described in mitochondria previously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17624330", "endSection": "abstract" } ] }, { "body": "Is Calcium/Calmodulin dependent protein kinase II (CaMKII) involved in cardiac arrhythmias and heart failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24077098", "http://www.ncbi.nlm.nih.gov/pubmed/23279377", "http://www.ncbi.nlm.nih.gov/pubmed/18556468", "http://www.ncbi.nlm.nih.gov/pubmed/19333131", "http://www.ncbi.nlm.nih.gov/pubmed/19919992", "http://www.ncbi.nlm.nih.gov/pubmed/23781262", "http://www.ncbi.nlm.nih.gov/pubmed/22453965", "http://www.ncbi.nlm.nih.gov/pubmed/22578240", "http://www.ncbi.nlm.nih.gov/pubmed/21174213", "http://www.ncbi.nlm.nih.gov/pubmed/16610345", "http://www.ncbi.nlm.nih.gov/pubmed/19482609", "http://www.ncbi.nlm.nih.gov/pubmed/22514276", "http://www.ncbi.nlm.nih.gov/pubmed/23862619", "http://www.ncbi.nlm.nih.gov/pubmed/21742790", "http://www.ncbi.nlm.nih.gov/pubmed/17704163", "http://www.ncbi.nlm.nih.gov/pubmed/21276796", "http://www.ncbi.nlm.nih.gov/pubmed/22009705", "http://www.ncbi.nlm.nih.gov/pubmed/23613689", "http://www.ncbi.nlm.nih.gov/pubmed/20194790", "http://www.ncbi.nlm.nih.gov/pubmed/23789646", "http://www.ncbi.nlm.nih.gov/pubmed/23159442", "http://www.ncbi.nlm.nih.gov/pubmed/17124532", "http://www.ncbi.nlm.nih.gov/pubmed/21098440", "http://www.ncbi.nlm.nih.gov/pubmed/23877259" ], "ideal_answer": [ "Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase expressed abundantly in the heart. CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias. ", "Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase expressed abundantly in the heart. CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias.", "Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias.The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005954", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017871", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004683", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054729", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054737", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054734", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054732" ], "type": "yesno", "id": "5502abd1e9bde69634000008", "snippets": [ { "offsetInBeginSection": 1307, "offsetInEndSection": 1740, "text": "In human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca(2+) leak. In the transition from hypertrophy to HF, the diastolic Ca(2+) leak increases and disturbed Ca(2+) cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23877259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an enzyme with important regulatory functions in the heart and brain, and its chronic activation can be pathological. CaMKII activation is seen in heart failure, and can directly induce pathological changes in ion channels, Ca(2+) handling and gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24077098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "In the recent years, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was suggested to be associated with cardiac hypertrophy and heart failure but also with arrhythmias both in animal models as well as in the human heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23862619", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 455, "text": "Calcium-calmodulin-dependent protein kinase II (CaMKII) has emerged as a central mediator of cardiac stress responses which may serve several critical roles in the regulation of cardiac rhythm, cardiac contractility and growth. Sustained and excessive activation of CaMKII during cardiac disease has, however, been linked to arrhythmias, and maladaptive cardiac remodeling, eventually leading to heart failure (HF) and sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23789646", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 469, "text": "Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781262", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 669, "text": "From recent studies, it appears evident that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca(2+) and redox stress, affecting individual ion channels and thereby leading to electrical instability in the heart. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613689", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 94, "text": "CaMKII activation is proarrhythmic in heart failure where myocardium is stretched.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279377", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 613, "text": "The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159442", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 425, "text": "Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is up-regulated in heart failure and has been shown to cause I(Na) gating changes that mimic those induced by a point mutation in humans that is associated with combined long QT and Brugada syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514276", "endSection": "abstract" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1735, "text": "CaMKII-dependent phosphorylation of Na(V)1.5 at multiple sites (including Thr-594 and Ser-516) appears to be required to evoke loss-of-function changes in gating that could contribute to acquired Brugada syndrome-like effects in heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514276", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 479, "text": "Because CaMKII expression and activity are increased in cardiac hypertrophy, heart failure, and during arrhythmias both in animal models as well as in the human heart a clinical significance of CaMKII is implied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22453965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 391, "text": "The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742790", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 791, "text": "In our opinion, the multifunctional Ca and calmodulin-dependent protein kinase II (CaMKII) has emerged as a molecule to watch, in part because a solid body of accumulated data essentially satisfy Koch's postulates, showing that the CaMKII pathway is a core mechanism for promoting myocardial hypertrophy and heart failure. Multiple groups have now confirmed the following: (1) that CaMKII activity is increased in hypertrophied and failing myocardium from animal models and patients; (2) CaMKII overexpression causes myocardial hypertrophy and HF and (3) CaMKII inhibition (by drugs, inhibitory peptides and gene deletion) improves myocardial hypertrophy and HF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276796", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1117, "text": " In contrast, inhibiting the CaMKII pathway appears to reduce arrhythmias and improve myocardial responses to pathological stimuli. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276796", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 625, "text": "In this review, we discuss the important role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the regulation of RyR2-mediated Ca(2+) release. In particular, we examine how pathological activation of CaMKII can lead to an increased risk of sudden arrhythmic death. Finally, we discuss how reduction of CaMKII-mediated RyR2 hyperactivity might reduce the risk of arrhythmias and may serve as a rationale for future pharmacotherapeutic approaches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22578240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "Transgenic (TG) Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) \u03b4(C) mice develop systolic heart failure (HF). CaMKII regulates intracellular Ca(2+) handling proteins as well as sarcolemmal Na(+) channels. We hypothesized that CaMKII also contributes to diastolic dysfunction and arrhythmias via augmentation of the late Na(+) current (late I(Na)) in early HF (8-week-old TG mice).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21174213", "endSection": "abstract" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1788, "text": "Thus, late I(Na) inhibition appears to be a promising option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to be increased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21174213", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 522, "text": "We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098440", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1785, "text": "CONCLUSIONS: our results suggest that Ca(2+)/calmodulin-dependent protein kinase II phosphorylation of RyR2 Ca(2+) release channels at S2814 plays an important role in arrhythmogenesis and sudden cardiac death in mice with heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability and myocardial dysfunction remain uncertain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20194790", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 328, "text": "Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias. We hypothesized that CaMKII contributes to arrhythmias and underlying cellular events and that inhibition of CaMKII reduces cardiac arrhythmogenesis in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19919992", "endSection": "abstract" }, { "offsetInBeginSection": 1786, "offsetInEndSection": 2145, "text": "We conclude that CaMKII contributes to cardiac arrhythmogenesis in TG CaMKIIdelta(C) mice having heart failure and suggest the increased SR Ca leak as an important mechanism. Moreover, CaMKII inhibition reduces cardiac arrhythmias in vitro and in vivo and may therefore indicate a potential role for future antiarrhythmic therapies warranting further studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19919992", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 760, "text": "Ca2+/calmodulin dependent protein kinase II (CaMKII) can phosphorylate RyR2 and modulate its activity. This phosphorylation positively modulates cardiac inotropic function but in extreme situations such as heart failure, elevated CaMKII activity can adversely increase Ca2+ release from the SR and lead to arrhythmogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19482609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase expressed abundantly in the heart. CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333131", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 392, "text": "Under stress conditions, excessive CaMKII activity promotes heart failure and arrhythmias, in part through actions at Ca(2+) homeostatic proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18556468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 482, "text": "Ca-calmodulin-dependent protein kinase II (CaMKII) was recently shown to alter Na(+) channel gating and recapitulate a human Na(+) channel genetic mutation that causes an unusual combined arrhythmogenic phenotype in patients: simultaneous long QT syndrome and Brugada syndrome. CaMKII is upregulated in heart failure where arrhythmias are common, and CaMKII inhibition can reduce arrhythmias. Thus, CaMKII-dependent channel modulation may contribute to acquired arrhythmic disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17704163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "In heart failure (HF), Ca(2+)/calmodulin kinase II (CaMKII) expression is increased. Altered Na(+) channel gating is linked to and may promote ventricular tachyarrhythmias (VTs) in HF. Calmodulin regulates Na(+) channel gating, in part perhaps via CaMKII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17124532", "endSection": "abstract" }, { "offsetInBeginSection": 1649, "offsetInEndSection": 1750, "text": "Thus, CaMKII-dependent regulation of Na(+) channel function may contribute to arrhythmogenesis in HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17124532", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 1050, "text": "Recent findings that CaMKII expression in the heart changes during hypertrophy, heart failure, myocardial ischemia, and infarction suggest that CaMKII may be a viable therapeutic target for patients suffering from common forms of heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16610345", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 467, "text": " Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23781262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19919992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19919992", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 313, "text": "CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Calcium/calmodulin-dependent protein kinase II contributes to cardiac arrhythmogenesis in heart failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19919992", "endSection": "title" }, { "offsetInBeginSection": 355, "offsetInEndSection": 668, "text": "From recent studies, it appears evident that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca(2+) and redox stress, affecting individual ion channels and thereby leading to electrical instability in the heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Ryanodine receptor phosphorylation, calcium/calmodulin-dependent protein kinase II, and life-threatening ventricular arrhythmias.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22578240", "endSection": "title" }, { "offsetInBeginSection": 128, "offsetInEndSection": 312, "text": "CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333131", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 612, "text": "The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Calcium-calmodulin kinase II mediates digitalis-induced arrhythmias.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009705", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19919992", "endSection": "abstract" } ] }, { "body": "What is the lay name of the treatment for CCSVI (chronic cerebro-spinal venous insufficiency) in multiple sclerosis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22687168", "http://www.ncbi.nlm.nih.gov/pubmed/21803799", "http://www.ncbi.nlm.nih.gov/pubmed/21856578", "http://www.ncbi.nlm.nih.gov/pubmed/22088659", "http://www.ncbi.nlm.nih.gov/pubmed/21679067", "http://www.ncbi.nlm.nih.gov/pubmed/21687341", "http://www.ncbi.nlm.nih.gov/pubmed/21838669", "http://www.ncbi.nlm.nih.gov/pubmed/23202144", "http://www.ncbi.nlm.nih.gov/pubmed/20351675", "http://www.ncbi.nlm.nih.gov/pubmed/22640501", "http://www.ncbi.nlm.nih.gov/pubmed/21755134", "http://www.ncbi.nlm.nih.gov/pubmed/23523158", "http://www.ncbi.nlm.nih.gov/pubmed/21839654", "http://www.ncbi.nlm.nih.gov/pubmed/22648477", "http://www.ncbi.nlm.nih.gov/pubmed/21136256", "http://www.ncbi.nlm.nih.gov/pubmed/21808631", "http://www.ncbi.nlm.nih.gov/pubmed/23034121", "http://www.ncbi.nlm.nih.gov/pubmed/20373339", "http://www.ncbi.nlm.nih.gov/pubmed/22951366", "http://www.ncbi.nlm.nih.gov/pubmed/21107001", "http://www.ncbi.nlm.nih.gov/pubmed/23380649", "http://www.ncbi.nlm.nih.gov/pubmed/23354606", "http://www.ncbi.nlm.nih.gov/pubmed/19958985", "http://www.ncbi.nlm.nih.gov/pubmed/23402260", "http://www.ncbi.nlm.nih.gov/pubmed/21876515", "http://www.ncbi.nlm.nih.gov/pubmed/22155803", "http://www.ncbi.nlm.nih.gov/pubmed/23301864" ], "ideal_answer": [ "The so-called \"LIberation therapy\" is in fact Endovascular Treatment and consists of PTA (Percutaneous Transluminal Angioplasty), which is dilatation of the internal jugular and/or azygous veins by a catheter venography. Stent placement is optional but has been strongly advised against as being dangerous." ], "exact_answer": [ "LIberation therapy" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2377", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103" ], "type": "factoid", "id": "515df199298dcd4e5100002a", "snippets": [ { "offsetInBeginSection": 130, "offsetInEndSection": 366, "text": "patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523158", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Although it is debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients undergo endovascular treatment (ET) of CCSVI", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23380649", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Endovascular treatment of CCSVI in patients with multiple sclerosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354606", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23354606", "endSection": "sections.0" }, { "offsetInBeginSection": 21, "offsetInEndSection": 282, "text": "Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) has been proposed to be associated with Multiple Sclerosis (MS). Zamboni et\u00a0al reported significant improvement in neurological outcomes in MS patients who underwent Percutaneous Transluminal Angioplasty (PTA)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23301864", "endSection": "sections.0" }, { "offsetInBeginSection": 243, "offsetInEndSection": 434, "text": "Our open-label study included 94 MS patients who fulfilled ultrasound sonographic criteria required for CCSVI. The internal jugular and/or azygous veins by a catheter venography were dilated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23202144", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Disability caused by multiple sclerosis is associated with the number of extra cranial venous stenoses: possible improvement by venous angioplasty. Results of a prospective study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23202144", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Clinical improvement after extracranial venoplasty in multiple sclerosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22951366", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 218, "text": "This study proposed to prospectively evaluate safety and clinical changes in outpatient endovascular treatment in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22951366", "endSection": "sections.0" }, { "offsetInBeginSection": 204, "offsetInEndSection": 359, "text": "Twenty-nine patients with clinically definite relapsing-remitting MS underwent percutaneous transluminal angioplasty for CCSVI, outside a clinical relapse.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22687168", "endSection": "sections.0" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1495, "text": "The European Society of Neurosonology and Cerebral Hemodynamics (ESNCH) has considerable concerns regarding the accuracy of the proposed criteria for CCSVI in MS. Therefore, any potentially harmful interventional treatment such as transluminal angioplasty and/or stenting should be strongly discouraged.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22648477", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Catheter venography and endovascular treatment of chronic cerebrospinal venous insufficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22640501", "endSection": "title" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1103, "text": "The work of Dr. Zamboni, et al, who reported that treating the venous stenoses causing CCSVI with angioplasty resulting in significant improvement in the symptoms and quality of life of patients with MS (2", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22640501", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Endovascular treatment of patients with chronic cerebrospinal venous insufficiency and multiple sclerosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155803", "endSection": "title" }, { "offsetInBeginSection": 478, "offsetInEndSection": 639, "text": "Endovascular treatment (percutaneous transluminal angioplasty (PTA) with or without stenting) of CCSVI was reported to be feasible with a minor complication rate", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155803", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Safety of endovascular treatment of chronic cerebrospinal venous insufficiency:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088659", "endSection": "title" }, { "offsetInBeginSection": 699, "offsetInEndSection": 933, "text": "For patients treated primarily, 87% (208 of 239) had angioplasty, and 11% (26 of 239) had stent placement; 5 patients were not treated. Of patients with restenosis, 50% (9 of 18) had angioplasty, and 50% (9 of 18) had stent placement.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088659", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "An endovascular treatment of Chronic Cerebro-Spinal Venous Insufficiency in multiple sclerosis patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876515", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 223, "text": "In this study, the mid-term results (6 month follow-up) of the endovascular treatment in patients with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and multiple sclerosis (MS) were prospectively evaluated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876515", "endSection": "sections.0" }, { "offsetInBeginSection": 233, "offsetInEndSection": 407, "text": "Thirty-six patients with confirmed MS and CCSVI underwent endovascular treatment by the means of the uni- or bilateral jugular vein angioplasty with optional stent placement.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876515", "endSection": "sections.0" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1045, "text": "stent implantation into the jugular vein,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876515", "endSection": "sections.0" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1351, "text": "As the debate about CCSVI and its relationship to MS continues, the complications and risks associated with venous stenting and angioplasty in jugular and azygous veins are becoming clearer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856578", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 274, "text": "Chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS). The objective of the study was to see if percutaneous transluminal angioplasty (PTA) of duplex-detected lesions, of the internal jugular and/or azygous veins, was safe,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21839654", "endSection": "sections.0" }, { "offsetInBeginSection": 434, "offsetInEndSection": 602, "text": "CCSVI theory has generated a scientific and mass media debate with a great hope for the miracle of a new possible endovascular treatment of MS (\"liberation procedure\").", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838669", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Internal jugular thrombosis post venoplasty for chronic cerebrospinal venous insufficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803799", "endSection": "title" }, { "offsetInBeginSection": 900, "offsetInEndSection": 990, "text": "The treatment based on the CCSVI theory has appealingly been called \"liberation treatment\"", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21755134", "endSection": "sections.0" }, { "offsetInBeginSection": 184, "offsetInEndSection": 330, "text": "MS patients (261 women; mean age 45.4 years, range 21-79) with CCSVI underwent endovascular treatment of 1012 venous lesions during 495 procedures", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679067", "endSection": "sections.0" }, { "offsetInBeginSection": 360, "offsetInEndSection": 495, "text": "While balloon angioplasty was preferred, 98 stents were implanted in 76 patients for lesion recoil, restenosis, or suboptimal dilation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679067", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 138, "text": "The aim of this report is to assess the safety of endovascular treatment 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"http://linkedlifedata.com/resource/umls/relation/R119944384", "o": "http://linkedlifedata.com/resource/umls/id/C0271829" } ], "ideal_answer": [ "Thyroid hormone abnormalities are characteristic to Pendred syndrome. Hypothyroidism is the most common thyroid hormone abnormality in Pendred syndrome. Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, goiter and a partial defect in iodide organification." ], "exact_answer": [ "thyroid hormone abnormalities" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006728" ], "type": "factoid", "id": "53148a07dae131f847000002", "snippets": [ { "offsetInBeginSection": 154, "offsetInEndSection": 363, "text": "Loss or reduction of function mutations of SLC26A4 underlie Pendred syndrome, a disorder invariably leading to hearing loss with enlarged vestibular aqueducts and in some patients to hypothyroidism and goiter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23235354", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 752, "text": "Goiter development and hypothyroidism vary among affected individuals and seem to be partially dependent on nutritional iodide intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21511235", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 1063, "text": "Elucidation of the molecular basis of Pendred syndrome and the function of pendrin has provided unexpected novel insights into the pathophysiology of the inner ear, thyroid hormone synthesis, and chloride/bicarbonate exchange in the kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21511235", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 833, "text": "Thyroid goiter was found in 46.5% of cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20822748", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Biallelic mutations of SLC26A4 (encoding pendrin) cause Pendred syndrome (PS), an autosomal recessive genetic disorder with deafness and goiter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20583162", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 620, "text": "From age 15 years, her thyroid gland showed progressive enlargement accompanied by elevation of serum thyroglobulin reaching 10-fold the normal amount. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20583162", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1457, "text": "In summary, a molecularly confirmed PS patient showed goiter progression accompanied by elevated serum thyroglobulin and increased thyroidal iodine uptake, but normal serum TSH levels and normal iodine organification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20583162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "A coherent organization of differentiation proteins is required to maintain an appropriate thyroid function in the Pendred thyroid.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20501687", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Pendred syndrome is an autosomal recessive disorder defined by sensorineural deafness, goiter and a partial organification defect of iodide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22116361", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 611, "text": "The clinical phenotype of patients with Pendred syndrome and the fact that pendrin can mediate iodide efflux in transfected cells suggest that this anion exchanger may be involved in mediating iodide efflux into the follicular lumen, a key step in thyroid hormone biosynthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22116361", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 813, "text": "Results of immunoblot and immunofluorescence experiments reveal that TSH and forskolin rapidly increase pendrin abundance at the plasma membrane through the protein kinase A pathway in PCCL-3 rat thyroid cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109890", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1360, "text": "These results demonstrate that pendrin translocates to the membrane in response to TSH and suggest that it may have a physiological role in apical iodide transport and thyroid hormone synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109890", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 202, "text": "Mutations in the SLC26A4 gene, coding for the anion transporter pendrin, are responsible for Pendred syndrome, characterized by congenital sensorineural deafness and dyshormonogenic goiter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20834201", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, goiter and a partial defect in iodide organification. Goiter development and hypothyroidism vary and appear to depend on nutritional iodide intake. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20298745", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 570, "text": "Pendrin is mainly expressed in the thyroid, the inner ear, and the kidney. In the thyroid, pendrin localizes to the apical membrane of thyrocytes, where it may be involved in mediating iodide efflux. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20298745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Mutations of SLC26A4 cause an enlarged vestibular aqueduct, nonsyndromic deafness, and deafness as part of Pendred syndrome. SLC26A4 encodes pendrin, an anion exchanger located in the cochlea, thyroid, and kidney. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19692489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Genetic causes of goiter and deafness: Pendred syndrome in a girl and cooccurrence of Pendred syndrome and resistance to thyroid hormone in her sister.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19318451", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 290, "text": "Goiter and deafness can be associated in some genetic syndromes, e.g. Pendred syndrome (PS) and resistance to thyroid hormone (RTH). PS is an autosomal recessive disorder characterized by goiter and sensorineural hearing impairment with an enlarged vestibular aqueduct bilaterally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19318451", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 1011, "text": "The elder sister had an elevated TSH level at newborn screening followed by subclinical hypothyroidism, childhood-onset goiter, and bilateral progressive sensorineural hearing impairment with enlarged vestibular aqueducts, consistent with a diagnosis of PS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19318451", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1769, "text": "This is the first report of the cooccurrence, in the same individual, of PS and RTH, two genetic syndromes both associated with goiter and hearing impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19318451", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 314, "text": "Its diagnosis requires identification of the classical triad of symptoms, including hypoacusis, thyroid goitre and iodine organification defect in the thyroid, which may lead to thyroid functional disorders of hypothyroidism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19205523", "endSection": "abstract" }, { "offsetInBeginSection": 1598, "offsetInEndSection": 1741, "text": "Endocrine examination showed hypothyroidism in 5, its subclinical form in 1, diffuse thyroid goitre in 4 and nodular thyroid goiter in 2 cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19205523", "endSection": "abstract" }, { "offsetInBeginSection": 1115, "offsetInEndSection": 1298, "text": "Biallelic mutations in the SLC26A4 gene lead to Pendred syndrome, an autosomal recessive disorder characterized by sensorineural deafness, goiter, and impaired iodide organification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19196800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Thyroidectomy in a patient with multinodular dyshormonogenetic goitre--a case of Pendred syndrome confirmed by mutations in the PDS/SLC26A4 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19189692", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "We report a young woman with genetically confirmed Pendred syndrome and discuss the current therapeutic strategies of dyshormonogenetic goitre.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19189692", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 709, "text": "Management of a patient with Pendred syndrome requires careful follow-up and regular imaging of the thyroid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19189692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing impairment, presence of goiter, and a partial defect in iodide organification, which may be associated with insufficient thyroid hormone synthesis. Goiter development and development of hypothyroidism are variable and depend on nutritional iodide intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18692402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Pendred syndrome (PS) is an autosomal recessive disease that is characterized by congenital sensorineural hearing loss, goiter, and a partial iodine organification defect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17697873", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 803, "text": "Levels of thyroid hormones were essentially normal in all patients: 2 patients had goiters and/or elevated serum thyroglobulin levels, whereas 2 other patients had positive thyroid antibodies and a positive perchlorate discharge test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17697873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Pendred syndrome, defined as the constellation of goiter, sensori-neural hearing loss, and positive perchlorate discharge test, is the most frequent cause of congenital deafness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17365057", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 589, "text": "Presuming the classic triad as the gold standard, we compared MRI findings in six such defined patients with six cases having goiter, hearing loss, and normal perchlorate discharge test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17365057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "For over 100 years after the first description of the disorder, the molecular pathology underlying the deafness and thyroid pathology in Pendred syndrome (PS) remained unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17120770", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 1143, "text": "We review the literature to identify genetic defects involved in the iodination process of the thyroid hormone synthesis, particularly defects in iodide transport from circulation into the thyroid cell, defects in iodide transport from the thyroid cell to the follicular lumen (Pendred syndrome), and defects of iodide organification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263499", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 1024, "text": "Among those causing dyshormonogenesis, the thyroid peroxidase and thyroglobulin genes were initially described, and more recently PDS (Pendred syndrome), NIS (sodium iodide symporter), and THOX2 (thyroid oxidase 2) gene defects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15863666", "endSection": "abstract" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 1967, "text": "Among permanent CH cases, those with a goitre (n = 27) had an iodine organification defect (n = 10), Pendred syndrome (n = 1), a defect of thyroglobulin synthesis (n = 8), or a defect of sodium iodine symporter (n = 1), and in seven patients no aetiology could be determined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15807875", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 315, "text": "Pendred syndrome consists in sensorineural deafness, goiter and impaired thyroid hormone synthesis while in EVA thyroid function seems to be preserved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15279074", "endSection": "abstract" }, { "offsetInBeginSection": 1312, "offsetInEndSection": 1465, "text": "All patients harbouring mutations in the SLC26A4 gene had goiter and a positive perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15279074", "endSection": "abstract" }, { "offsetInBeginSection": 1763, "offsetInEndSection": 1987, "text": "Patients with mutations in the SLC26A4 gene had larger thyroid volume (p<0.002), higher serum thyroglobulin (Tg) levels (p<0.002) and greater radioiodine discharge after perchlorate (p=0.09) than patients without mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15279074", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 148, "text": "The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11375792", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1041, "text": "Two patients were hypothyroid, two individuals were euthyroid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11375792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and thyroid goiter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10650967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Pendred syndrome is an autosomal recessive disorder characterized by the association between sensorineural hearing loss and thyroid swelling or goitre and is likely to be the most common form of syndromic deafness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9618167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10571950", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 313, "text": "Pendred syndrome consists in sensorineural deafness, goiter and impaired thyroid hormone synthesis while in EVA thyroid function seems to be preserved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15279074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Biallelic mutations of SLC26A4 (encoding pendrin) cause Pendred syndrome (PS), an autosomal recessive genetic disorder with deafness and goiter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20583162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Pendred syndrome (PS) is an autosomal recessive disease that is characterized by congenital sensorineural hearing loss, goiter, and a partial iodine organification defect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17697873", "endSection": "abstract" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1140, "text": "Individuals were assigned affected status based on the characteristic clinical features of Pendred's syndrome, namely the presence of congenital sensorineural hearing loss and the appearance in early life of a goitre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8706311", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of long QT Jervell and Lange-Nielsen syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10593671", "http://www.ncbi.nlm.nih.gov/pubmed/23400408", "http://www.ncbi.nlm.nih.gov/pubmed/9341873", "http://www.ncbi.nlm.nih.gov/pubmed/12132284", "http://www.ncbi.nlm.nih.gov/pubmed/11140949", "http://www.ncbi.nlm.nih.gov/pubmed/10077519", "http://www.ncbi.nlm.nih.gov/pubmed/1917338", "http://www.ncbi.nlm.nih.gov/pubmed/10704188", "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "http://www.ncbi.nlm.nih.gov/pubmed/23392653", "http://www.ncbi.nlm.nih.gov/pubmed/7721491", "http://www.ncbi.nlm.nih.gov/pubmed/18595190", "http://www.ncbi.nlm.nih.gov/pubmed/11140992", "http://www.ncbi.nlm.nih.gov/pubmed/9302275", "http://www.ncbi.nlm.nih.gov/pubmed/10654932", "http://www.ncbi.nlm.nih.gov/pubmed/1721555", "http://www.ncbi.nlm.nih.gov/pubmed/12051962" ], "ideal_answer": [ "Jervell and Lange-Nielsen long QT syndrome (JLNS) is characterized by autosomal recessive mode of inheritance" ], "exact_answer": [ "autosomal recessive" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029593", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008133", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582" ], "type": "factoid", "id": "52eea4dcc8da89891000000c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 245, "text": "Homozygous or compound heterozygous mutations in KCNQ1 cause Jervell and Lange-Nielsen syndrome, a rare, autosomal-recessive form of long-QT syndrome characterized by deafness, marked QT prolongation, and a high risk of sudden death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23392653", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 514, "text": "KCNQ1 is associated with two different entities of LQTS, the autosomal-dominant Romano-Ward syndrome (RWS), and the autosomal-recessive Jervell and Lange-Nielsen syndrome (JLNS) characterized by bilateral deafness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Jervell and Lange-Nielsen syndrome (JLNS) is characterized by sensorineural deafness, QT prolongation, abnormal T waves, ventricular tachyarrhythmias, and autosomal recessive inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12051962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterised by profound congenital sensorineural deafness and prolongation of the QT interval on the electrocardiogram, representing abnormal ventricular repolarisation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11140949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Jervell and Lange-Nielsen syndrome (MIM 220400; JLNS), is a rare form of profound congenital deafness combined with syncopal attacks and sudden death due to prolonged QTc; it is an autosomal recessive trait. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10704188", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 612, "text": "Different mutations in KVLQT1 cause the dominant Romano-Ward (RW) syndrome and the recessive Jervell and Lange-Nielsen (JLN) syndrome, which, in addition to cardiac abnormalities, includes congenital deafness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9302275", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 449, "text": "The Jervell and Lange-Nielsen syndrome (JLNS) is characterized by prolongation of the QT interval, deafness, and autosomal-recessive inheritance, and the Romano-Ward syndrome is characterized by a prolonged QT interval, autosomal-dominant inheritance, and no deafness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10593671", "endSection": "abstract" } ] }, { "body": "List programs suitable for protein docking", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23198780", "http://www.ncbi.nlm.nih.gov/pubmed/23436713", "http://www.ncbi.nlm.nih.gov/pubmed/23862697", "http://www.ncbi.nlm.nih.gov/pubmed/23633577", "http://www.ncbi.nlm.nih.gov/pubmed/23812908", "http://www.ncbi.nlm.nih.gov/pubmed/23351099", "http://www.ncbi.nlm.nih.gov/pubmed/17444519", "http://www.ncbi.nlm.nih.gov/pubmed/23451944", "http://www.ncbi.nlm.nih.gov/pubmed/16933295", "http://www.ncbi.nlm.nih.gov/pubmed/23712937", "http://www.ncbi.nlm.nih.gov/pubmed/23836482", "http://www.ncbi.nlm.nih.gov/pubmed/24108416", "http://www.ncbi.nlm.nih.gov/pubmed/23808933", "http://www.ncbi.nlm.nih.gov/pubmed/24050689", "http://www.ncbi.nlm.nih.gov/pubmed/15215358", "http://www.ncbi.nlm.nih.gov/pubmed/24063890", "http://www.ncbi.nlm.nih.gov/pubmed/24187131", "http://www.ncbi.nlm.nih.gov/pubmed/23775700", "http://www.ncbi.nlm.nih.gov/pubmed/23873600", "http://www.ncbi.nlm.nih.gov/pubmed/23818491", "http://www.ncbi.nlm.nih.gov/pubmed/23647909", "http://www.ncbi.nlm.nih.gov/pubmed/23813626", "http://www.ncbi.nlm.nih.gov/pubmed/23590204", "http://www.ncbi.nlm.nih.gov/pubmed/24123140", "http://www.ncbi.nlm.nih.gov/pubmed/11841293", "http://www.ncbi.nlm.nih.gov/pubmed/24266324", "http://www.ncbi.nlm.nih.gov/pubmed/23829357" ], "ideal_answer": [ "Macromolecular docking is the computational modelling of the quaternary structure of complexes formed by two or more interacting biological macromolecules. Protein\u2013protein complexes are the most commonly attempted targets of such modelling, followed by protein\u2013nucleic acid complexes.\nThe ultimate goal of docking is the prediction of the three-dimensional structure of the macromolecular complex of interest as it would occur in a living organism. Docking itself only produces plausible candidate structures. These candidates must be ranked using methods such as scoring functions to identify structures that are most likely to occur in nature.\nNowadays there a lot of programs suitable for proteins docking such as CSBB-ConeExclusion, HADDOCK, ZDOCK, GalaxyDock, PHASE, DockRank, HotLig, SOL, AutodockVina, DockoMatic, DockoMatic, DockTrina, CAVITY, LiGenDock and DOCK." ], "exact_answer": [ [ "CSBB-ConeExclusion" ], [ "HADDOCK" ], [ "ZDOCK" ], [ "GalaxyDock" ], [ "PHASE" ], [ "DockRank" ], [ "HotLig" ], [ "SOL" ], [ "AutodockVina" ], [ "DockoMatic" ], [ "DockTrina" ], [ "CAVITY" ], [ "LiGenDock" ], [ "DOCK" ], [ "DISCORE" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005785", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005047", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016560", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0022406", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048278", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000059", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0022614", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0022615", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019542" ], "type": "list", "id": "53355befd6d3ac6a34000046", "snippets": [ { "offsetInBeginSection": 786, "offsetInEndSection": 935, "text": "We present CSBB-ConeExclusion, a methodology and computer program which provides a measure of the applicability of solution dockings to solid support", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24266324", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 409, "text": "The structure of the \u03b11I-peptide complex was investigated using data from NMR, small angle x-ray scattering, and size exclusion chromatography that were used to generate and validate a model of the complex using the data-driven docking program, HADDOCK (High Ambiguity Driven Biomolecular Docking). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24187131", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 218, "text": "We report the performance of our approaches for protein-protein docking and interface analysis in CAPRI rounds 20-26. At the core of our pipeline was the ZDOCK program for rigid-body protein-protein docking", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24123140", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 281, "text": "GalaxyDock protein-ligand docking program is introduced. GalaxyDock performs conformational space annealing (CSA) global optimization to find the optimal binding pose of a ligand both in the rigid-receptor mode and the flexible-receptor mode", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24108416", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 858, "text": "Utilizing NMR titration data, we generated the structural models of S100B-FGF2 complex from the computational docking program, HADDOCK which were further proved stable during 15ns unrestrained molecular dynamics (MD) simulations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24063890", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 720, "text": "Thereafter, all molecules were docked into the newly generated active site environment of the selected protein using glide docking program, and the 3D-QSAR analysis was performed in PHASE program utilizing the docking based alignment of the molecules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24050689", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 908, "text": "DockRank uses interface residues predicted by partner-specific sequence homology-based protein-protein interface predictor (PS-HomPPI), which predicts the interface residues of a query protein with a specific interaction partner. We compared the performance of DockRank with several state-of-the-art docking scoring functions using Success Rate (the percentage of cases that have at least one near-native conformation among the top m conformations) and Hit Rate (the percentage of near-native conformations that are included among the top m conformations). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23873600", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 520, "text": "In this study, we developed a novel scoring program, HotLig, which applies the Connolly surface of a protein to calculate hydrophobic interaction and paired pharmacophore interactions with ligands. In addition to molecular surface distance, ligand-contacting areas and hydrogen-bond angles were also introduced to the scoring functions in HotLig", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23862697", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 182, "text": "a method called residue contact frequency (RCF), which uses the complex structures generated by the protein-protein docking algorithm ZDOCK to predict interface residues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836482", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 470, "text": "devoted to results obtained by the docking program SOL and the post-processing program DISCORE at the CSAR benchmark. SOL and DISCORE programs are described. SOL is the original docking program developed on the basis of the genetic algorithm, MMFF94 force field, rigid protein, precalculated energy grid including desolvation in the frame of simplified GB model, vdW, and electrostatic interactions and taking into account the ligand internal strain energy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23829357", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 747, "text": "improves the binding energy scoring by the local energy optimization of the ligand docked pose and a simple linear regression on the base of available experimental data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23829357", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 567, "text": "The template-based methods showed similar performance to a docking method (ZDOCK) when the latter was allowed one prediction for each complex, but when the same number of predictions was allowed for each method, the docking approach outperformed template-based approaches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818491", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 441, "text": "VinaMPI is a massively parallel Message Passing Interface (MPI) program based on the multithreaded virtual docking program AutodockVina, and is used to distribute tasks while multithreading is used to speed-up individual docking tasks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23813626", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 978, "text": "Prime and the binding energy function in YASARA suggested it could be possible to evaluate the quality of the orthosteric binding site based on the prediction of relative binding energies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23812908", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 188, "text": " is a free and open source application that unifies a suite of software programs within a user-friendly graphical user interface (GUI) to facilitate molecular docking experiments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23808933", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 955, "text": "This article presents DockTrina, a novel protein docking method for modeling the 3D structures of nonsymmetrical triangular trimers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23775700", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 606, "text": "To account for the important docking interactions between the UBSAs ligand and hCA II enzyme, a molecular docking program AutoDock Vina is used. The molecular docking results obtained by AutoDock Vina revealed that the docked conformer has root mean square deviation value less than 1.50 \u00c5 compared to X-ray crystal structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23712937", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 564, "text": "Four possible binding pockets (Pocket A, B, C, and D) at the stalk region of hemagglutinin were detected and defined using the CAVITY program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23647909", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 527, "text": "Within this context, low-resolution shape data obtained from either ion-mobility mass spectrometry (IM-MS) or SAXS experiments have been integrated into the conventional scoring function of the information-driven docking program HADDOCK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633577", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 199, "text": "a novel de novo design program, called LiGen, we developed a docking program, LiGenDock, based on pharmacophore models of binding sites, including a non-enumerative docking algorithm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23590204", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 379, "text": "we present the functionalities of LiGenDock and its accompanying module LiGenPocket, aimed at the binding site analysis and structure-based pharmacophore definition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23590204", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 443, "text": "Here we describe the application of the program AutoDock to the design of a focused library that was used in the \"click chemistry in-situ\" generation of the most potent noncovalent inhibitor of the native enzyme acetylcholinesterase (AChE) yet developed (K(d) = ~100 fM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23451944", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 989, "text": " the method yields improved success over the standard DOCK energy function for pose identification across a large test set of experimental co-crystal structures, for crossdocking, and for database enrichment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23436713", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 739, "text": "The pose prediction success rate of each docking program alone was found in this trial to be 55% for Autodock, 58% for DOCK, and 64% for Vina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23351099", "endSection": "abstract" } ] }, { "body": "Which genes have been found mutated in Gray platelet syndrome patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23861251", "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "http://www.ncbi.nlm.nih.gov/pubmed/17209061", "http://www.ncbi.nlm.nih.gov/pubmed/21765411", "http://www.ncbi.nlm.nih.gov/pubmed/21765413", "http://www.ncbi.nlm.nih.gov/pubmed/21765412", "http://www.ncbi.nlm.nih.gov/pubmed/23100277" ], "ideal_answer": [ "The genetic defects responsible for gray platelet syndrome are mutations in the genes NBEAL2, GATA1 and GFI1B.", "The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.\nA nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.\nX-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation." ], "exact_answer": [ [ "neurobeachin-like 2", "NBEAL2" ], [ "GATA1" ], [ "GFI1B" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:225", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030220", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036345", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:2218", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036344", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055652" ], "type": "list", "id": "52f89f4f2059c6d71c00004e", "snippets": [ { "offsetInBeginSection": 145, "offsetInEndSection": 315, "text": "We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24325358", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 279, "text": "The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100277", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 370, "text": "Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21765412", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 665, "text": "Linkage analysis revealed a 63 cM region on the X chromosome between markers G10578 and DXS6797, which segregated with the platelet phenotype and included the GATA1 gene. Sequencing of GATA1 revealed a G-to-A mutation at position 759 corresponding to amino acid change Arg216Gln. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "We identified a family with gray platelet syndrome (GPS) segregating as a sex-linked trait. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209061", "endSection": "title" } ] }, { "body": "Does dasatinib promote or inhibit T-cell proliferation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19066329", "http://www.ncbi.nlm.nih.gov/pubmed/18395492", "http://www.ncbi.nlm.nih.gov/pubmed/17962511", "http://www.ncbi.nlm.nih.gov/pubmed/19056158", "http://www.ncbi.nlm.nih.gov/pubmed/18619726", "http://www.ncbi.nlm.nih.gov/pubmed/19016717", "http://www.ncbi.nlm.nih.gov/pubmed/18413841" ], "ideal_answer": [ "Dasatinib inhibits T-cell proliferation" ], "exact_answer": [ "inhibits" ], "concepts": [ "http://www.biosemantics.org/jochem#4274027", "http://amigo.geneontology.org/amigo/term/GO:0042098", "http://amigo.geneontology.org/amigo/term/GO:0042130", "http://amigo.geneontology.org/amigo/term/GO:0042102", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069439", "http://www.biosemantics.org/jochem#4244012", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4274027" ], "type": "factoid", "id": "56c85ed65795f9a73e000012", "snippets": [ { "offsetInBeginSection": 1020, "offsetInEndSection": 1138, "text": "Dasatinib inhibited antigen-specific proliferation of murine CD4(+) and CD8(+) transgenic T cells in vitro and in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19056158", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 566, "text": "Herein, we show that dasatinib inhibits TCR-mediated signal transduction, cellular proliferation, cytokine production, and in vivo T-cell responses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962511", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1190, "text": "Both dasatinib and staurosporine inhibited T-cell activation, proliferation, cytokine production, and degranulation in a dose-dependent manner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18413841", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 564, "text": "Herein, we show that dasatinib inhibits TCR-mediated signal transduction, cellular proliferation, cytokine production, and in vivo T-cell responses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962511", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962511", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Dasatinib inhibits the proliferation and function of CD4+CD25+ regulatory T cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19016717", "endSection": "title" }, { "offsetInBeginSection": 501, "offsetInEndSection": 871, "text": "T-cell functions including proliferation, activation and cytokine production were all uniformly inhibited in the presence of dasatinib. We also demonstrated inhibition of TCR signalling through Src-family kinase LCK, and predicted that inhibition of LCK and other kinases involved in T-cell signalling by dasatinib is responsible for the suppression of T-cell function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18395492", "endSection": "abstract" } ] }, { "body": "Does SCRIB deregulation promote cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21643016", "http://www.ncbi.nlm.nih.gov/pubmed/14767561", "http://www.ncbi.nlm.nih.gov/pubmed/22169974", "http://www.ncbi.nlm.nih.gov/pubmed/21965329", "http://www.ncbi.nlm.nih.gov/pubmed/24276238", "http://www.ncbi.nlm.nih.gov/pubmed/19041750", "http://www.ncbi.nlm.nih.gov/pubmed/18641685", "http://www.ncbi.nlm.nih.gov/pubmed/23730214", "http://www.ncbi.nlm.nih.gov/pubmed/21549346" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7659777", "o": "C36345" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1514542", "o": "http://linkedlifedata.com/resource/umls/label/A7659777" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7659777", "o": "Protein Deregulation" } ], "ideal_answer": [ "Yes, deregulation of scribble promotes cancer." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.uniprot.org/uniprot/SCRIB_DANRE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.uniprot.org/uniprot/LAP4_DROME" ], "type": "yesno", "id": "53314c98d6d3ac6a3400003b", "snippets": [ { "offsetInBeginSection": 134, "offsetInEndSection": 211, "text": "human homologs of Drosophila dlg, scrib, and lgl are cancer-associated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14767561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Aberrant overexpression of the cell polarity module scribble in human cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549346", "endSection": "title" }, { "offsetInBeginSection": 140, "offsetInEndSection": 318, "text": "we show that Scrib is nearly universally overexpressed in cultured tumor cell lines and genetically disparate cancer patient series compared with matched normal tissues in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549346", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 939, "text": "These data uncover a previously unrecognized exploitation of Scrib for aberrant tumor cell motility and invasion, thus potentially contributing to disease progression in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549346", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 737, "text": "oss of miR-296 causes aberrantly increased and mislocalized Scrib in human tumors, resulting in exaggerated random cell migration and tumor cell invasiveness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21643016", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 904, "text": "Scrib levels predict tumor relapse in hepatocellular carcinoma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21643016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Scrib heterozygosity predisposes to lung cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276238", "endSection": "title" }, { "offsetInBeginSection": 754, "offsetInEndSection": 859, "text": "loss of Scrib and activated oncogenic KRas cooperate in vivo, resulting in more aggressive lung tumors, l", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276238", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 463, "text": "Scribble, a product of a well-known tumor suppressor gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23730214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "CD74-dependent deregulation of the tumor suppressor scribble in human epithelial and breast cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23730214", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 358, "text": " scribble (SCRIB) complexes) is intricately related to advanced stages of tumour progression and invasiveness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22169974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "SCRIB expression is deregulated in human prostate cancer,", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21965329", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 582, "text": "Scrib heterozygosity initiated prostate hyperplasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21965329", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1153, "text": "The clinical significance of the work in mice was highlighted by our observation that SCRIB deregulation strongly correlated with poor survival in human prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21965329", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 1051, "text": "we demonstrate that scribble inhibits breast cancer formation and that deregulation of polarity pathways promotes dysplastic and neoplastic growth in mammals by disrupting morphogenesis and inhibiting cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19041750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19041750", "endSection": "title" }, { "offsetInBeginSection": 637, "offsetInEndSection": 743, "text": "loss of Scribble promotes invasion of cells through extracellular matrix in an organotypic culture system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18641685", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1195, "text": "Scribble expression is decreased in many invasive human cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18641685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18641685", "endSection": "title" } ] }, { "body": "Is cardiac magnetic resonance imaging indicated in the pre-participation screening of athletes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22375189", "http://www.ncbi.nlm.nih.gov/pubmed/21567995", "http://www.ncbi.nlm.nih.gov/pubmed/22375228", "http://www.ncbi.nlm.nih.gov/pubmed/22653640", "http://www.ncbi.nlm.nih.gov/pubmed/19734502", "http://www.ncbi.nlm.nih.gov/pubmed/20599016", "http://www.ncbi.nlm.nih.gov/pubmed/16831826", "http://www.ncbi.nlm.nih.gov/pubmed/20048491", "http://www.ncbi.nlm.nih.gov/pubmed/10663764", "http://www.ncbi.nlm.nih.gov/pubmed/19055989", "http://www.ncbi.nlm.nih.gov/pubmed/24029371", "http://www.ncbi.nlm.nih.gov/pubmed/21118665", "http://www.ncbi.nlm.nih.gov/pubmed/20705486", "http://www.ncbi.nlm.nih.gov/pubmed/15689345", "http://www.ncbi.nlm.nih.gov/pubmed/21791458", "http://www.ncbi.nlm.nih.gov/pubmed/22983606", "http://www.ncbi.nlm.nih.gov/pubmed/22853772", "http://www.ncbi.nlm.nih.gov/pubmed/16004915", "http://www.ncbi.nlm.nih.gov/pubmed/15166900", "http://www.ncbi.nlm.nih.gov/pubmed/12446071", "http://www.ncbi.nlm.nih.gov/pubmed/18325444", "http://www.ncbi.nlm.nih.gov/pubmed/23897528", "http://www.ncbi.nlm.nih.gov/pubmed/21278396", "http://www.ncbi.nlm.nih.gov/pubmed/20833588", "http://www.ncbi.nlm.nih.gov/pubmed/16914373", "http://www.ncbi.nlm.nih.gov/pubmed/18208827", "http://www.ncbi.nlm.nih.gov/pubmed/21782775", "http://www.ncbi.nlm.nih.gov/pubmed/23097483", "http://www.ncbi.nlm.nih.gov/pubmed/21486912", "http://www.ncbi.nlm.nih.gov/pubmed/22457200" ], "ideal_answer": [ "Currently cardiac magnetic resonance imaging is not indicated in the pre-participation screening of athletes. However the potential of this imaging technique to provide new information on cardiac function morphology and myocardial composition, in particular with regard to myocardial fibrosis, gets it potentially suitable to be applied in the pre-participation screening of athletes" ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019028", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054874", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ], "type": "yesno", "id": "531d3dc0267d7dd053000005", "snippets": [ { "offsetInBeginSection": 1858, "offsetInEndSection": 2112, "text": "As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029371", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 872, "text": "Finally we will address the role of CMR in pre-participation screening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23097483", "endSection": "abstract" } ] }, { "body": "Is imatinib an antidepressant drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20676553", "http://www.ncbi.nlm.nih.gov/pubmed/19110398", "http://www.ncbi.nlm.nih.gov/pubmed/22593820", "http://www.ncbi.nlm.nih.gov/pubmed/16403813", "http://www.ncbi.nlm.nih.gov/pubmed/22460758", "http://www.ncbi.nlm.nih.gov/pubmed/16566359", "http://www.ncbi.nlm.nih.gov/pubmed/21938530", "http://www.ncbi.nlm.nih.gov/pubmed/17554495", "http://www.ncbi.nlm.nih.gov/pubmed/22035758", "http://www.ncbi.nlm.nih.gov/pubmed/22831984", "http://www.ncbi.nlm.nih.gov/pubmed/22487918", "http://www.ncbi.nlm.nih.gov/pubmed/15966213", "http://www.ncbi.nlm.nih.gov/pubmed/20442314", "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "http://www.ncbi.nlm.nih.gov/pubmed/22484890", "http://www.ncbi.nlm.nih.gov/pubmed/20726677", "http://www.ncbi.nlm.nih.gov/pubmed/20407930", "http://www.ncbi.nlm.nih.gov/pubmed/21607924", "http://www.ncbi.nlm.nih.gov/pubmed/23394826", "http://www.ncbi.nlm.nih.gov/pubmed/18506179", "http://www.ncbi.nlm.nih.gov/pubmed/22110503", "http://www.ncbi.nlm.nih.gov/pubmed/21087500", "http://www.ncbi.nlm.nih.gov/pubmed/22678007", "http://www.ncbi.nlm.nih.gov/pubmed/19628568", "http://www.ncbi.nlm.nih.gov/pubmed/22135725" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/724", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3066", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/541", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2610", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/513", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/612", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/441", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/251", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/795", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3277", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/782", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/possibleDrug", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/2806", "o": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12798671", "o": "Imatinib" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17885052", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12790183", "o": "IMATINIB" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A1989038", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasSideEffect", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00619", "o": "http://linkedlifedata.com/resource/pubmed/mesh/Anxiety" } ], "ideal_answer": [ "No. Imatinib is a tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably Chronic myelogenous leukemia (CML) and Gastrointestinal stromal tumor (GIST)." ], "exact_answer": "no", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007202", "http://www.biosemantics.org/jochem#4275840" ], "type": "yesno", "id": "51542e84d24251bc05000083", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 325, "text": "Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Surgery remains the elective treatment. We retrospectively compared two group of patients, who underwent surgery for GIST before and after Imatinib advent in order to analyze the recurrence and survival rate.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22487918", "endSection": "sections.0" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1368, "text": "Adjuvant imatinib 400 mg/day for 3 years duration is a standard treatment in all patients with significant risk of recurrence following resection of primary GISTs", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22831984", "endSection": "sections.0" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1585, "text": "R1 surgery (versus R0) alone is not an indication for adjuvant imatinib in low-risk GIST.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22831984", "endSection": "sections.0" }, { "offsetInBeginSection": 1931, "offsetInEndSection": 2005, "text": "Treatment is not recommended in an imatinib-insensitive D842V-mutated GIST", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22831984", "endSection": "sections.0" }, { "offsetInBeginSection": 310, "offsetInEndSection": 701, "text": "Prognostic factors such as tumor size, mitotic rate and presence of metastases may provide an indication for adjuvant imatinib mesylate (IM) treatment. Here we present a young patient with a large GIST with high-risk features who is in complete remission after surgical excision and adjuvant IM treatment. This patient is the only colon-located CD117-positive case where IM was administered.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22678007", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Imatinib mesylate is the sole BCR-ABL tyrosine kinase inhibitor approved as first-line treatment of accelerated-phase (AP) chronic myeloid leukemia (CML).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22460758", "endSection": "sections.0" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1686, "text": "imatinib mesylate could be a therapeutic target of strategies against osteosarcoma tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22135725", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Allogeneic hematopoietic stem cell transplantation (HSCT) is well-established as a potentially curative treatment for patients who have chronic myeloid leukemia. The success of imatinib and other tyrosine kinase inhibitors (TKI) as initial therapy has changed the treatment paradigm for this disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22035758", "endSection": "sections.0" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1219, "text": "Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21938530", "endSection": "sections.0" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1440, "text": "Ki67 correlated with time to recurrence (p=0.022). Ki67 >11% was taken as the indication to start imatinib chemotherapy (sensitivity 61.5%, specificity 92.0%, p=0.022).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21607924", "endSection": "sections.0" }, { "offsetInBeginSection": 410, "offsetInEndSection": 554, "text": "Significant pharmacokinetic interactions have already been shown between St. John's Wort (SJW) and the anticancer drugs imatinib and irinotecan.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394826", "endSection": "sections.0" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1440, "text": "for CML we analysed imatinib, dasatinib and nilotinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073206", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 253, "text": "Imatinib mesylate, an orally administered kinase inhibitor that targets the Kit (CD117) protein, currently has 10 approved indications including treatment of chronic myelogenous leukemia and metastatic gastrointestinal stromal tumors (GIST).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20726677", "endSection": "sections.0" }, { "offsetInBeginSection": 539, "offsetInEndSection": 903, "text": "The drugs were assessed according to clinical evidence on efficacy and safety, based on Micromedex categorization, on systematic reviews and meta-analyses. Indications present in the legal documentation were compared to the indications approved by regulatory agencies. RESULTS: Bevacizumab, capecitabine, cetuximab, erlotinib, rituximab, imatinib, and temozolomide", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20676553", "endSection": "sections.0" }, { "offsetInBeginSection": 540, "offsetInEndSection": 580, "text": "Bcr-Abl, an oncogene responsible for CML", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442314", "endSection": "sections.0" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1545, "text": "Bcr-Abl-expressing cells showed resistance to death activated by spindle defects, reversed by imatinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442314", "endSection": "sections.0" }, { "offsetInBeginSection": 275, "offsetInEndSection": 399, "text": "Imatinib, an oral tyrosine kinase inhibitor (TKI), is first-line treatment in patients with metastatic or unresectable GIST.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20407930", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 130, "text": "Surgical indication for metastatic gastrointestinal stromal tumor (GIST) treated with imatinib is not yet established.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19628568", "endSection": "sections.0" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1285, "text": "Surgery of residual disease upon best clinical response seems associated with survival benefit compared with historical controls in similar patient collectives treated with imatinib alone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19628568", "endSection": "sections.0" }, { "offsetInBeginSection": 11, "offsetInEndSection": 167, "text": "To explore the effect of preoperative imatinib mesylate (IM) in patients with unresectable or locally advanced primary gastrointestinal stromal tumor (GIST)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19110398", "endSection": "sections.0" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1054, "text": "The patient had been diagnosed 14 months earlier and had been submitted to surgery, followed by adjuvant radiotherapy and temozolomide-based chemotherapy. On clinical suspicion of recurrence 5 months later, magnetic resonance imaging (MRI) revealed a lesion at the site of preceded surgery, which was treated by imatinib mesylate", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17554495", "endSection": "sections.0" }, { "offsetInBeginSection": 1512, "offsetInEndSection": 1678, "text": "Radical surgery remains the most effective method of GIST treatment. In inoperable/metastatic lesion the treatment of choice is tyrosinase kinase inhibitor--imatinib.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16566359", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16403813", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Imatinib, an inhibitor of the tyrosine kinase activity of c-kit, was used as an adjuvant chemotherapy in two patients who underwent curative surgery for recurrent gastrointestinal stromal tumors.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15966213", "endSection": "sections.0" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1369, "text": "Adjuvant imatinib 400 mg/day for 3 years duration is a standard treatment in all patients with significant risk of recurrence following resection of primary GISTs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22831984", "endSection": "sections.0" } ] }, { "body": "What is the function of the MTH1 enzyme in cancer cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17071637", "http://www.ncbi.nlm.nih.gov/pubmed/17207658", "http://www.ncbi.nlm.nih.gov/pubmed/23468525", "http://www.ncbi.nlm.nih.gov/pubmed/16621731", "http://www.ncbi.nlm.nih.gov/pubmed/21787772", "http://www.ncbi.nlm.nih.gov/pubmed/22556419", "http://www.ncbi.nlm.nih.gov/pubmed/24277933", "http://www.ncbi.nlm.nih.gov/pubmed/22790201", "http://www.ncbi.nlm.nih.gov/pubmed/20144704", "http://www.ncbi.nlm.nih.gov/pubmed/16716086", "http://www.ncbi.nlm.nih.gov/pubmed/21195604", "http://www.ncbi.nlm.nih.gov/pubmed/23295485", "http://www.ncbi.nlm.nih.gov/pubmed/22757673", "http://www.ncbi.nlm.nih.gov/pubmed/20542142", "http://www.ncbi.nlm.nih.gov/pubmed/17425590", "http://www.ncbi.nlm.nih.gov/pubmed/16607562", "http://www.ncbi.nlm.nih.gov/pubmed/21389046", "http://www.ncbi.nlm.nih.gov/pubmed/17917452" ], "ideal_answer": [ "The MTH1 protein catalyzes hydrolysis of oxidatively damaged purine nucleotides including 8-hydroxy-dGTP to the monophosphates. The MTH1 protein seems to act as an important defense system against mutagenesis, carcinogenesis, and cell death induced by oxidized purine nucleotides." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.uniprot.org/uniprot/8ODP_MOUSE", "http://www.uniprot.org/uniprot/8ODP_RAT", "http://www.uniprot.org/uniprot/MTH1_YEAST", "http://www.uniprot.org/uniprot/8ODP_HUMAN" ], "type": "summary", "id": "551af9106b348bb82c000002", "snippets": [ { "offsetInBeginSection": 220, "offsetInEndSection": 268, "text": "the glucose-responsive transcription factor Mth1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23468525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Human MTH1 (hMTH1) is an enzyme that hydrolyses several oxidized purine nucleoside triphosphates to their corresponding nucleoside monophosphates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23295485", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 428, "text": " We have recently shown that oncogenic RAS-induced DNA damage and attendant premature senescence can be prevented by overexpressing human MutT Homolog 1 (MTH1), the major mammalian detoxifier of the oxidized DNA precursor, 8-oxo-dGTP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22790201", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Human Mut T Homolog 1 (MTH1): a roadblock for the tumor-suppressive effects of oncogenic RAS-induced ROS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22790201", "endSection": "title" }, { "offsetInBeginSection": 602, "offsetInEndSection": 667, "text": "MutT homolog 1 (oxidized purine nucleoside triphosphatase, MTH1),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22757673", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 803, "text": "MTH1 cleaves 8-oxo-dGTP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22556419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "MTH1 hydrolyzes oxidized nucleotide triphosphates, thereby preventing them from being incorporated into DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21787772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "MutT-related proteins, including Escherichia coli MutT and the human MTH1 (NUDT1), degrade 8-oxo-7, 8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP) to 8-oxo-dGMP and thereby prevent mutations caused by the misincorporation of 8-oxoguanine into DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21389046", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 325, "text": "MTH1 (or NUDT1) are also involved in the repair of 7,8-dihydro-8-oxoguanine (8-oxo-G), previous studies,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21195604", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 645, "text": "To counteract such deleterious effects of nucleotide pool damage, mammalian cells possess MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase and related enzymes, thus minimizing the accumulation of oxidized bases in cellular DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20542142", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 928, "text": "These results indicate that all three of the human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20144704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Human MTH1, an oxidized purine nucleoside triphosphatase, hydrolyzes 8-oxo-dGTP thereby preventing its misincorporation into DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17917452", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 922, "text": "MTH1 is a mammalian ortholog of Escherichia coli MutT, which hydrolyzes 8-oxo-dGTP to its monophosphate form in nucleotide pools, thereby preventing incorporation of the mutagenic substrate into DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17425590", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 419, "text": "Several pathways are involved in the repair of DNA lesions caused by oxidative stress, such as the base excision repair system (BER), which repairs mutation involving 8-oxoguanine and comprises the MUTYH, OGG1 and MTH1 genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17207658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "The MTH1 protein catalyzes hydrolysis of oxidatively damaged purine nucleotides including 8-hydroxy-dGTP to the monophosphates. The MTH1 protein seems to act as an important defense system against mutagenesis, carcinogenesis, and cell death induced by oxidized purine nucleotides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17071637", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 756, "text": "In mammalian cells, MTH1 and NUDT5 proteins degrade 8-oxoGTP and 8-oxoGDP to 8-oxoGMP, which is an unusable form for RNA synthesis. In a search for proteins functioning at the RNA level, polynucleotide phosphorylase (PNP) protein has been suggested to be a good candidate for such a role. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16716086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Human MTH1 protein hydrolyzes oxidized purine nucleotides 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dGTP), 2-OH-dATP or their ribo-forms to their monophosphates, thus minimizing replicational and transcriptional errors both in the nuclei and mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16607562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2'-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2'-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16621731", "endSection": "abstract" } ] }, { "body": "Are ultraconserved elements depleted among copy number variants (CNVs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "http://www.ncbi.nlm.nih.gov/pubmed/18957701", "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "http://www.ncbi.nlm.nih.gov/pubmed/21092253" ], "ideal_answer": [ "Yes. Interestingly, human ultraconserved elements (UCEs) have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs). These elements may be interpreted as hallmarks for dose-sensitive genes, particularly for those genes whose gain or loss may be directly implied in neurodevelopmental disorders. Therefore, their presence in genomic imbalances of unknown effect might be suggestive of a clinically relevant condition" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056915" ], "type": "yesno", "id": "55413142182542114d000002", "snippets": [ { "offsetInBeginSection": 362, "offsetInEndSection": 794, "text": "We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison. Here, we report that nonexonic UCEs are also depleted among 10 of 11 recent genomewide data sets of human CNVs, including 3 obtained with strategies permitting greater precision in determining the extents of CNVs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18957701", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 578, "text": "Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1763, "text": "We propose that these elements may be interpreted as hallmarks for dose-sensitive genes, particularly for those genes whose gain or loss may be directly implied in neurodevelopmental disorders. Therefore, their presence in genomic imbalances of unknown effect might be suggestive of a clinically relevant condition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 579, "text": "Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 581, "text": "We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18957701", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 580, "text": "We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18957701", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 566, "text": "Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 716, "text": "Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 639, "text": "The depletion of UCEs among copy number variation as well as the significant under-representation of single-nucleotide polymorphisms (SNPs) within UCEs have also revealed their evolutional and functional importance indicating their potential impact on disease, such as cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "endSection": "abstract" } ] }, { "body": "Is the microRNA 132 (miR-132) involved in brain pathologies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19458943", "http://www.ncbi.nlm.nih.gov/pubmed/21813326", "http://www.ncbi.nlm.nih.gov/pubmed/22315408", "http://www.ncbi.nlm.nih.gov/pubmed/21945804", "http://www.ncbi.nlm.nih.gov/pubmed/23001356", "http://www.ncbi.nlm.nih.gov/pubmed/19557767", "http://www.ncbi.nlm.nih.gov/pubmed/21807765", "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "http://www.ncbi.nlm.nih.gov/pubmed/20010955", "http://www.ncbi.nlm.nih.gov/pubmed/23144617", "http://www.ncbi.nlm.nih.gov/pubmed/21136867", "http://www.ncbi.nlm.nih.gov/pubmed/17314675" ], "triples": [ { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/citations/10071047", "o": "Brain" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10430839", "o": "Brain" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/12566285", "o": "http://purl.uniprot.org/pubmed/12566285" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2745360", "o": "http://linkedlifedata.com/resource/umls/label/A17397784" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17397784", "o": "mmu-mir-132" } ], "ideal_answer": [ "Yes. MicroRNA 132 (miR-132), is involved in brain pathologies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002545", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001927", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001928", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002534", "http://www.disease-ontology.org/api/metadata/DOID:936", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001921", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0007420", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010336" ], "type": "yesno", "id": "5156be5ed24251bc05000087", "snippets": [ { "offsetInBeginSection": 1562, "offsetInEndSection": 1740, "text": "miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315408", "endSection": "sections.0" }, { "offsetInBeginSection": 430, "offsetInEndSection": 889, "text": "micro-RNAs encoding miR-9, miR-124a, miR-125b, miR-128, miR-132 and miR-219 are abundantly represented in fetal hippocampus, are differentially regulated in aged brain, and an alteration in specific micro-RNA complexity occurs in Alzheimer hippocampus. These data are consistent with the idea that altered micro-RNA-mediated processing of messenger RNA populations may contribute to atypical mRNA abundance and neural dysfunction in Alzheimer's disease brain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17314675", "endSection": "sections.0" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1576, "text": "Levels of several microRNA (miR-10a, -10b, -212, -132, -495) were significantly altered. One of them (miR-132) has been reported to be highly inducible by growth factors and to be a key regulator of neurite outgrowth. Moreover, miR-132-recognition sequences were detected in the mRNA transcripts of two differentially expressed proteins. MicroRNA may thus represent novel biomarkers for neuronal malfunction and potential therapeutic targets for human neurodegenerative diseases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21136867", "endSection": "sections.0" }, { "offsetInBeginSection": 627, "offsetInEndSection": 769, "text": "Expression of key neuronal microRNAs-including mir-9/9*, mir-124 and mir-132-is repressed in the brains of human HD patients and mouse models.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458943", "endSection": "sections.0" }, { "offsetInBeginSection": 224, "offsetInEndSection": 372, "text": "To determine if production of miR-132 is regulated by neuronal activity its expression in mouse brain was monitored by quantitative RT-PCR (RT-qPCR)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19557767", "endSection": "sections.0" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1208, "text": "Expression levels of primary and mature-miR-132 increased significantly between postnatal Days 10 and 24. We conclude that miR-132 is an activity-dependent microRNA in vivo, and may contribute to the long-lasting proteomic changes required for experience-dependent neuronal plasticity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19557767", "endSection": "sections.0" }, { "offsetInBeginSection": 384, "offsetInEndSection": 529, "text": "We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21945804", "endSection": "sections.0" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1553, "text": "Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21945804", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Preconditioning describes the ischemic stimulus that triggers an endogenous, neuroprotective response that protects the brain during a subsequent severe ischemic injury, a phenomenon known as 'tolerance'.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010955", "endSection": "sections.0" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1542, "text": "Downregulation of miR-132 is consistent with our finding that preconditioning ischemia induces a rapid increase in MeCP2 protein, but not mRNA, in mouse cortex. These studies reveal that ischemic preconditioning regulates expression of miRNAs and their predicted targets in mouse brain cortex, and further suggest that miRNAs and MeCP2 could serve as effectors of ischemic preconditioning-induced tolerance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010955", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "endSection": "sections.0" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1302, "text": "Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "endSection": "sections.0" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1599, "text": "transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "endSection": "sections.0" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1630, "text": "miR-132 directly targets the neuronal splicing factor polypyrimidine tract-binding protein 2 (PTBP2), which protein levels were increased in PSP patients. miR-132 overexpression or PTBP2 knockdown similarly affected endogenous 4R:3R-tau ratios in neuronal cells. Finally, we provide evidence that miR-132 is inversely correlated with PTBP2 during post-natal brain development at the time when 4R-tau becomes expressed. Taken together, these results suggest that changes in the miR-132/PTBP2 pathway could contribute to the abnormal splicing of tau exon 10 in the brain, and sheds light into the potential role played by miRNAs in a subset of tauopathies.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21807765", "endSection": "sections.0" }, { "offsetInBeginSection": 7, "offsetInEndSection": 545, "text": "reports of microRNA (miR) modulators of both neuronal and immune processes (here termed NeurimmiRs) predict therapeutic potential for manipulating NeurimmiR levels in diseases affecting both the immune system and higher brain functions, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and anxiety-related disorders. In our opinion, NeurimmiRs that function within both the nervous and the immune systems, such as miR-132 and miR-124, may act as 'negotiators' between these two interacting compartments.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813326", "endSection": "sections.0" } ] }, { "body": "What is an approximate number of CTCF binding sites in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22955980", "http://www.ncbi.nlm.nih.gov/pubmed/22829947", "http://www.ncbi.nlm.nih.gov/pubmed/15229244", "http://www.ncbi.nlm.nih.gov/pubmed/15670593", "http://www.ncbi.nlm.nih.gov/pubmed/8034708", "http://www.ncbi.nlm.nih.gov/pubmed/11854173", "http://www.ncbi.nlm.nih.gov/pubmed/23707059", "http://www.ncbi.nlm.nih.gov/pubmed/11076856", "http://www.ncbi.nlm.nih.gov/pubmed/22709888" ], "ideal_answer": [ "The number of CTCF binding sites in the human genome lies between 31,000 and 50,000." ], "exact_answer": [ "30,000-50,000" ], "concepts": [ "http://www.uniprot.org/uniprot/CTCF_HUMAN", "http://www.uniprot.org/uniprot/CTCF_RAT", "http://www.uniprot.org/uniprot/CTCF_MOUSE", "http://www.uniprot.org/uniprot/CTCF_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001665" ], "type": "factoid", "id": "533c38b3c45e133714000009", "snippets": [ { "offsetInBeginSection": 265, "offsetInEndSection": 384, "text": "To study CTCF multivalency in\u00a0vivo, we define ZF binding requirements at \u223c50,000 genomic sites in primary lymphocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707059", "endSection": "abstract" }, { "offsetInBeginSection": 1436, "offsetInEndSection": 1521, "text": "However, only ~3,700 out of the ~5,700 CTCFL- and ~31,000 CTCF-binding sites overlap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22709888", "endSection": "abstract" } ] }, { "body": "Does cucumber lower blood sugar in diabetics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21264099", "http://www.ncbi.nlm.nih.gov/pubmed/937227", "http://www.ncbi.nlm.nih.gov/pubmed/2620957", "http://www.ncbi.nlm.nih.gov/pubmed/19854256", "http://www.ncbi.nlm.nih.gov/pubmed/11451723", "http://www.ncbi.nlm.nih.gov/pubmed/17650589", "http://www.ncbi.nlm.nih.gov/pubmed/20614191", "http://www.ncbi.nlm.nih.gov/pubmed/22419465", "http://www.ncbi.nlm.nih.gov/pubmed/22416705", "http://www.ncbi.nlm.nih.gov/pubmed/8569244", "http://www.ncbi.nlm.nih.gov/pubmed/19276533", "http://www.ncbi.nlm.nih.gov/pubmed/22897583", "http://www.ncbi.nlm.nih.gov/pubmed/16179750" ], "ideal_answer": [ "Yes. Based on several scientific reports, ethanolic extract of cucumber and some other Cucurbitaceae plants are associated with a significant reduction of elevated blood glucose level, suggesting that cucumber could have antidiabetic activity." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001786", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018553" ], "type": "yesno", "id": "516c220e298dcd4e51000071", "snippets": [ { "offsetInBeginSection": 125, "offsetInEndSection": 411, "text": "The ethanolic extract of Cucumis sativus Linn, Cucumis melo utilissimum Roxb, Cucumis melo Linn, Benincasa hispida Thunb Cogn and Tricosanthes anguina Nees, when administered in 250 mg/kg dose, orally to rats failed to lower blood sugar or to depress the peak value, after glucose load.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2620957", "endSection": "sections.0" }, { "offsetInBeginSection": 615, "offsetInEndSection": 952, "text": "Ethanolic extract of Tricosanthes dioica Roxb plant caused a significant lowering of blood sugar in fasted rats and depressed the peak value in glucose loaded single and longterm fed groups of rats. The ethanolic extract of the aerial part of T. dioica also induced significant depression in the peak values in the glucose loaded models.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2620957", "endSection": "sections.0" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1087, "text": "The amount of sucrose in ordinary marinated foods, such as herring, cucumber, and common beet was negligible", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/937227", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Dietary saponins of sea cucumber ameliorate obesity, hepatic steatosis, and glucose intolerance in high-fat diet-fed mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22897583", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 271, "text": "In this study, we investigated the effects of saponins of sea cucumber (SSC) on high-fat diet-induced obesity, insulin resistance, and fatty liver in mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22897583", "endSection": "sections.0" }, { "offsetInBeginSection": 616, "offsetInEndSection": 879, "text": "Mice administrated with 0.1% SSC had significantly decreased serum glucose and insulin levels, lower homeostatic model assessment for insulin resistance index, and area under the blood glucose curve, suggesting that insulin sensitivity is enhanced by dietary SSC.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22897583", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "[Effects of sea cucumber cerebroside and its long-chain base on lipid and glucose metabolism in obese mice].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419465", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "OBJECTIVE: To investigate the effect of sea cucumber cerebroside(SCC) and its long-chain base(LCB) on lipid and glucose metabolism in obese mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419465", "endSection": "sections.0" }, { "offsetInBeginSection": 786, "offsetInEndSection": 907, "text": "CONCLUSIONS: Sea cucumber cerebroside and its long-chain base can improve the glucose and lipid metabolism in obese mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419465", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "The hitherto unknown glucose regulating role of three vegetable peels from cucurbitaceae family was evaluated. In a preliminary study, effects of ethanolic extracts of Cucurbita pepo, Cucumis sativus and Praecitrullus fistulosus peels were studied at 250 and 500\u00a0mg\u00a0kg(-1)\u00a0d(-1) for 15\u00a0days in the alterations in serum glucose and in hepatic lipid peroxidation (LPO) in male mice.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20614191", "endSection": "sections.0" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1086, "text": "All the three peel extracts nearly reversed most of these changes induced by alloxan suggesting their possible role in ameliorating diabetes mellitus and related changes in serum lipids.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20614191", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in streptozotocin-induced-diabetic rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19854256", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 347, "text": "Cucumis trigonus Roxb. (Cucurbitaceae) fruit is used in the Indian traditional medicine for the treatment of diabetes. Based on a number of reports on the blood glucose level reduction and the other complications of diabetes associated with some Cucurbitaceae plants, the antidiabetic effect of Cucumis trigonus fruit was investigated.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19854256", "endSection": "sections.0" }, { "offsetInBeginSection": 490, "offsetInEndSection": 632, "text": "The antidiabetic activity of aqueous extract of Cucumis trigonus fruit was evaluated by using normal and streptozotocin-induced-diabetic rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19854256", "endSection": "sections.0" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1512, "text": "The aqueous fruit extract of Cucumis trigonus has had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced-diabetic rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19854256", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Possible amelioration of atherogenic diet induced dyslipidemia, hypothyroidism and hyperglycemia by the peel extracts of Mangifera indica, Cucumis melo and Citrullus vulgaris fruits in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276533", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Hitherto unknown efficacy of the peel extracts of Mangifera indica (MI), Cucumis melo (CM) and Citrullus vulgaris (CV) fruits in ameliorating the diet-induced alterations in dyslipidemia, thyroid dysfunction and diabetes mellitus have been investigated in rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276533", "endSection": "sections.0" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1296, "text": "Rats, treated simultaneously with either of the peel extracts reversed the CCT-diet induced increase in the levels of tissue LPO, serum lipids, glucose, creatinine kinase-MB and decrease in the levels of thyroid hormones and insulin indicating their potential to ameliorate the diet induced alterations in serum lipids, thyroid dysfunctions and hyperglycemia/diabetes mellitus.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276533", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Role of pectin from cucumber (Cucumis sativus) in modulation of protein kinase C activity and regulation of glycogen metabolism in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17650589", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 518, "text": "The regulatory role of protein kinase C (PKC) in glycogen metabolism in pectin fed rats was investigated. Administration of pectin (5 g/kg body wt/day) from cucumber (Cucumis sativius L.) led to inhibitory effects on PKC activity in the liver of rats. In the brain and pancreas, PKC activity was significantly higher in pectin-treated rats as compared to the control group. Level of blood glucose was significantly lowered and the level of glycogen in the liver was significantly increased in pectin-administered rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17650589", "endSection": "sections.0" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1693, "text": "Addition of fermented milk (yogurt) and pickled cucumber to a breakfast with a high-glycemic index bread significantly lowered postprandial glycemia and insulinemia compared with the reference meal. In contrast, addition of regular milk and fresh cucumber had no favorable effect on the metabolic responses.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11451723", "endSection": "sections.0" }, { "offsetInBeginSection": 236, "offsetInEndSection": 461, "text": "Tolbutamide, Cucurbita ficifolia, Phaseolus vulgaris, Opuntia streptacantha, Spinacea oleracea, Cucumis sativus and Cuminum cyminum decrease significantly the area under the glucose tolerance curve and the hyperglycemic peak.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8569244", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Two unsaturated fatty acids with potent \u03b1-glucosidase inhibitory activity purified from the body wall of sea cucumber (Stichopus japonicus).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22416705", "endSection": "title" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1361, "text": "In this study, 2 fatty acids with strong \u03b1-glucosidase-inhibitory activity, 7(Z)-octadecenoic acid and 7(Z),10(Z)-octadecadienoic acid, were purified and identified from sea cucumber. Therefore, sea cucumber fatty acids can potentially be developed as a novel natural nutraceutical for the management of type-2 diabetes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22416705", "endSection": "sections.0" } ] }, { "body": "Which mutations in the cardiac isoform of the ryanodine receptor (RyR2) have been found to be related to CPVT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23498838", "http://www.ncbi.nlm.nih.gov/pubmed/21659649", "http://www.ncbi.nlm.nih.gov/pubmed/12919952", "http://www.ncbi.nlm.nih.gov/pubmed/15890976", "http://www.ncbi.nlm.nih.gov/pubmed/23152493", "http://www.ncbi.nlm.nih.gov/pubmed/18483626", "http://www.ncbi.nlm.nih.gov/pubmed/22828895", "http://www.ncbi.nlm.nih.gov/pubmed/14571276", "http://www.ncbi.nlm.nih.gov/pubmed/20676041", "http://www.ncbi.nlm.nih.gov/pubmed/23746327" ], "ideal_answer": [ "Recently, a novel CPVT RyR2 mutation, G230C, was found to increase the cytosolic, but not the luminal, Ca2+ sensitivity of single RyR2 channels in lipid bilayers. The novel RYR2-S4153R mutation has been implicated as a cause of CPVT and atrial fibrillation. A novel RyR2-V2475F mutation is associated with CPVT in humans. 3 CPVT mouse models are: RyR2-R2474S+/-, RyR2-N2386I+/-, and RyR2-L433P+/-. The E189D RyR2 mutation is causative for CPVT. A knock-in mouse model carrier of the R4496C mutation is the mouse equivalent to the R4497C mutations identified in CPVT families. Scanning of 12 Finnish CPVT probands identified three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in unaffected and control individuals. Three CPVT-linked human RyR2 (hRyR2) mutations are: S2246L, N4104K, and R4497C." ], "exact_answer": [ [ "RyR2-G230C" ], [ "RyR2-S4153R" ], [ "RyR2-V2475F" ], [ "RyR2-R2474S" ], [ "RyR2-N2386I" ], [ "RyR2-L433P" ], [ "RyR2-E189D" ], [ "RyR2-R4497C (RyR2-R4496C in the mouse)" ], [ "RyR2-V2306I," ], [ "RyR2-P4902L" ], [ "RyR2-R4959Q" ], [ "RyR2-S2246L" ], [ "RyR2-N4104K" ] ], "concepts": [ "http://www.uniprot.org/uniprot/RYR2_HUMAN" ], "type": "list", "id": "550712739d0faaa527000008", "snippets": [ { "offsetInBeginSection": 575, "offsetInEndSection": 737, "text": "Recently, a novel CPVT RyR2 mutation, G230C, was found to increase the cytosolic, but not the luminal, Ca2+ sensitivity of single RyR2 channels in lipid bilayers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746327", "endSection": "abstract" }, { "offsetInBeginSection": 1513, "offsetInEndSection": 1743, "text": "These data suggest that the G230C mutation enhances the propensity for SOICR by sensitizing the channel to luminal and cytosolic Ca2+ activation, and that G230C has an intrinsic structural impact on the N-terminal domains of RyR2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746327", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 765, "text": "The novel RYR2-S4153R mutation has been implicated as a cause of CPVT and atrial fibrillation. The mutation has been functionally characterized via store-overload-induced Ca(2+) release (SOICR) and tritium-labelled ryanodine ([(3)H]ryanodine) binding assays. The S4153R mutation enhanced propensity for spontaneous Ca(2+) release and reduced SOICR threshold but did not alter Ca(2+) activation of [(3)H]ryanodine binding, a common feature of other CPVT gain-of-function RYR2 mutations. We conclude that the S4153R mutation is a gain-of-function RYR2 mutation associated with a clinical phenotype characterized by both CPVT and atrial fibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23498838", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 535, "text": "To determine the molecular and cellular mechanisms by which a novel RyR2-V2475F mutation associated with CPVT in humans triggers Ca(2+)-dependent arrhythmias in whole hearts and intact mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152493", "endSection": "abstract" }, { "offsetInBeginSection": 1752, "offsetInEndSection": 1888, "text": "The mutation RyR2-V2475F is phenotypically strong among other CPVT mutations and produces heterogeneous mechanisms of RyR2 dysfunction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23152493", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 1117, "text": "We generated 3 knock-in mice with mutations introduced into RyR2 that result in leaky channels and cause exercise induced polymorphic ventricular tachycardia in humans [catecholaminergic polymorphic ventricular tachycardia (CPVT)]. We examined AF susceptibility in these three CPVT mouse models harboring RyR2 mutations to explore the role of diastolic SR Ca2+ leak in AF. AF was stimulated with an intra-esophageal burst pacing protocol in the 3 CPVT mouse models (RyR2-R2474S+/-, 70%; RyR2-N2386I+/-, 60%; RyR2-L433P+/-, 35.71%) but not in wild-type (WT) mice (P<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828895", "endSection": "abstract" }, { "offsetInBeginSection": 1300, "offsetInEndSection": 1917, "text": "The RyR2-G230C mutant exhibits similar biophysical defects compared with previously characterized CPVT mutations: decreased binding of the stabilizing subunit calstabin2 and a leftward shift in the Ca(2+) dependence for activation under conditions that simulate exercise, consistent with a \"leaky\" channel. Both RyR2-G230C and RyR2-P2328S channels exhibit normal luminal Ca(2+) activation. Thus, diastolic sarcoplasmic reticulum Ca(2+) leak caused by reduced calstabin2 binding and a leftward shift in the Ca(2+) dependence for activation by diastolic levels of cytosolic Ca(2+) is a common mechanism underlying CPVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21659649", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1527, "text": "A novel CPVT mutation, E189D, was identified. The E189D mutation does not alter the affinity of the channel for FKBP12.6, but it increases the propensity for store-overload-induced Ca(2+) release (SOICR). Furthermore, the E189D mutation enhances the basal channel activity of RyR2 and its sensitivity to activation by caffeine. The E189D RyR2 mutation is causative for CPVT and functionally increases the propensity for SOICR without altering the affinity for FKBP12.6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20676041", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 731, "text": "We found that mice heterozygous for the R2474S mutation in Ryr2 (Ryr2-R2474S mice) exhibited spontaneous generalized tonic-clonic seizures (which occurred in the absence of cardiac arrhythmias), exercise-induced ventricular arrhythmias, and sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483626", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1085, "text": " Thus, CPVT-associated mutant leaky Ryr2-R2474S channels in the brain can cause seizures in mice, independent of cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18483626", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 503, "text": "We screened 12 Finnish CPVT probands for mutations in these genes and identified three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in unaffected and control individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14571276", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 567, "text": "RyR2 mutations suggested to cause defective Ca2+ channel function have recently been identified in catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular dysplasia (ARVD) affected individuals. We report expression of three CPVT-linked human RyR2 (hRyR2) mutations (S2246L, N4104K, and R4497C) in HL-1 cardiomyocytes displaying correct targeting to the endoplasmic reticulum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12919952", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 942, "text": "We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15890976", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1645, "text": "These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15890976", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 940, "text": "We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15890976", "endSection": "abstract" } ] }, { "body": "Which population has a high frequency of the HLA-B*1502 allele?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16415921", "http://www.ncbi.nlm.nih.gov/pubmed/21424386", "http://www.ncbi.nlm.nih.gov/pubmed/15057820", "http://www.ncbi.nlm.nih.gov/pubmed/19915237", "http://www.ncbi.nlm.nih.gov/pubmed/19694795", "http://www.ncbi.nlm.nih.gov/pubmed/21306565", "http://www.ncbi.nlm.nih.gov/pubmed/20345939", "http://www.ncbi.nlm.nih.gov/pubmed/18637831", "http://www.ncbi.nlm.nih.gov/pubmed/21169036", "http://www.ncbi.nlm.nih.gov/pubmed/18855540", "http://www.ncbi.nlm.nih.gov/pubmed/22211527" ], "triples": [ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A18289792", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A7573122", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1257890", "o": "http://linkedlifedata.com/resource/umls/label/A7573122" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0103552", "o": "Population" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0103553", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0103554", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/keyword/POPULATIONS", "o": "POPULATIONS" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/mesh/Population", "o": "Population" } ], "ideal_answer": [ "HLA-B*1502 has a high frequency in Han Chinese and other Asian populations, except Japanese. (There is a strong association between human leucocyte antigen (HLA)-B*1502 and carbamazepine-induced Stevens-Johnson syndrome (SJS))." ], "exact_answer": [ "Han Chinese and other Asian populations, except Japanese" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044469", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011153", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005828", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005805", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005787", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044382" ], "type": "factoid", "id": "51542e6fd24251bc05000082", "snippets": [ { "offsetInBeginSection": 229, "offsetInEndSection": 438, "text": "A strong association between human leukocyte antigen (HLA)-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese, Thai, Malaysian and Indian populations, but not in Caucasian or Japanese populations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22211527", "endSection": "sections.0" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1129, "text": "found a strong association between HLA-B*1502 and CBZ-induced SJS/TEN in the Han Chinese population from central and northern China. Combined with previous studies of the southern Han Chinese subpopulation, our results suggest that HLA-B*1502 is strongly associated with CBZ-induced SJS/TEN in the whole Han Chinese population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21424386", "endSection": "sections.0" }, { "offsetInBeginSection": 274, "offsetInEndSection": 388, "text": "A strong association between HLA-B*1502 and carbamazepine-induced SJS/TEN has been identified in Chinese and Thai.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21306565", "endSection": "sections.0" }, { "offsetInBeginSection": 321, "offsetInEndSection": 487, "text": "In the present study, we conducted a pilot study to detect a possible association of oxcarbazepine (OXC)-induced MPE with HLA-B*1502 allele in Chinese Han population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169036", "endSection": "sections.0" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1591, "text": "observed an increased frequency of HLA-B*1502 allele in patients (44.44%) compared with tolerant controls (11.11%), although it failed to reach statistical significance (P=0.294). CONCLUSIONS: Our findings indicate that HLA-B*1502 allele may contribute to the genetic susceptibility to OXC-induced MPE in Chinese Han population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21169036", "endSection": "sections.0" }, { "offsetInBeginSection": 189, "offsetInEndSection": 479, "text": "A strong association between HLA-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case-control study was conducted to determine whether HLA-B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20345939", "endSection": "sections.0" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1283, "text": "Results from this study suggest that HLA-B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ-induced SJS and TEN.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20345939", "endSection": "sections.0" }, { "offsetInBeginSection": 169, "offsetInEndSection": 414, "text": "A strong association has been reported between human leucocyte antigen (HLA)-B*1502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-B*1502 is not a universal marker but is ethnicity-specific for Asians.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19915237", "endSection": "sections.0" }, { "offsetInBeginSection": 189, "offsetInEndSection": 308, "text": "the human leukocyte antigen HLA-B*1502 is associated with Stevens-Johnson syndrome (SJS) induced by CBZ in Han Chinese.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19694795", "endSection": "sections.0" }, { "offsetInBeginSection": 134, "offsetInEndSection": 265, "text": "the HLA allele B*1502 as a marker for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese,", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18855540", "endSection": "sections.0" }, { "offsetInBeginSection": 323, "offsetInEndSection": 525, "text": "This allele is seen in high frequency in many Asian populations other than Han Chinese, but there are few data on whether the allele is a marker for this severe outcome in anyone other than Han Chinese.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18855540", "endSection": "sections.0" }, { "offsetInBeginSection": 34, "offsetInEndSection": 186, "text": "a strong association between HLA-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) in Han Chinese, but not in Caucasian populations.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18637831", "endSection": "sections.0" }, { "offsetInBeginSection": 234, "offsetInEndSection": 363, "text": "A very strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been described in the Han Chinese population.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16415921", "endSection": "sections.0" }, { "offsetInBeginSection": 172, "offsetInEndSection": 394, "text": "there is a strong association in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and Stevens-Johnson syndrome induced by carbamazepine, a drug commonly prescribed for the treatment of seizures", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15057820", "endSection": "sections.0" } ] }, { "body": "What are the observations regarding telomere integrity and function in Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23571757", "http://www.ncbi.nlm.nih.gov/pubmed/15319283", "http://www.ncbi.nlm.nih.gov/pubmed/11591364", "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "http://www.ncbi.nlm.nih.gov/pubmed/19129235" ], "ideal_answer": [ "In Fanconi anemia patients, a higher rate of breakage at TTAGGG sequences in vivo is causing telomere erosion in differentiated cells. Moreover, it has been demonstrated that \u03b1IISp is important for telomere maintenance after DNA damage due to interstrand cross-links (ICL), localizing to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recruitment of the ICL repair protein, XPF, to damage-induced foci at telomeres. In telomerase-positive normal cells depleted of \u03b1IISp by siRNA or in Fanconi anemia, complementation group A (FANCA) cells, where \u03b1IISp levels are 35-40% of normal, ICL damage results in failure of XPF to localize to telomeres, with markedly increased telomere dysfunction-induced foci, and catastrophic loss of telomeres.", "A higher frequency of extra-chromosomic TTAGGG signals and of chromosome ends with undetectable TTAGGG repeats was observed in FA cells by fluorescence in situ hybridization (FISH), suggesting intensive breakage at telomeric sequences. This was proven by measuring the frequency of excess of telomeric signals per cell, which was 2.8-fold higher in FAWe now demonstrate that \u03b1IISp is also important for telomere maintenance after ICL damage. It localizes to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recruitment of the ICL repair protein, XPF, to damage-induced foci at telomeres. In telomerase-positive normal cells depleted of \u03b1IISp by siRNA or in Fanconi anemia, complementation group A (FA-A) cells, where \u03b1IISp levels are 35-40% of normal, ICL damage results in failure of XPF to localize to telomeres, markedly increased telomere dysfunction-induced foci, followed by catastrophic loss of telomeres" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13636", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010833", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010834", "http://www.disease-ontology.org/api/metadata/DOID:1062" ], "type": "summary", "id": "54edeb4394afd6150400000b", "snippets": [ { "offsetInBeginSection": 273, "offsetInEndSection": 895, "text": "We now demonstrate that \u03b1IISp is also important for telomere maintenance after ICL damage. It localizes to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recruitment of the ICL repair protein, XPF, to damage-induced foci at telomeres. In telomerase-positive normal cells depleted of \u03b1IISp by siRNA or in Fanconi anemia, complementation group A (FA-A) cells, where \u03b1IISp levels are 35-40% of normal, ICL damage results in failure of XPF to localize to telomeres, markedly increased telomere dysfunction-induced foci, followed by catastrophic loss of telomeres", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23571757", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 976, "text": "Restoration of \u03b1IISp levels to normal in FA-A cells corrects these deficiencies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23571757", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 350, "text": "previous works suggested an accelerated shortening of telomeres in FA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 890, "text": "A higher frequency of extra-chromosomic TTAGGG signals and of chromosome ends with undetectable TTAGGG repeats was observed in FA cells by fluorescence in situ hybridization (FISH), suggesting intensive breakage at telomeric sequences. This was proven by measuring the frequency of excess of telomeric signals per cell, which was 2.8-fold higher in FA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1087, "text": "Consistent with previous reports, quantitative FISH analysis showed an accelerated telomere shortening of 0.68 kb in FA, which occurred concurrently in both chromosome arms in a similar magnitude", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "abstract" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1314, "text": "Our data therefore suggest that the telomere erosion in FA is caused by a higher rate of breakage at TTAGGG sequences in vivo in differentiated cells, in addition to mere replicative shortening during lymphocyte proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1458, "text": "Consistent with impaired telomeres in FA patients, we observed a >10-fold increase in chromosome end fusions in FA compared to normal controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 538, "text": "Since previous works suggested an accelerated shortening of telomeres in FA, we have studied several markers of telomere integrity and function in FA patients and age-matched controls to get insights into the mechanisms and consequences of telomere erosion in FA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Accelerated telomere shortening in Fanconi anemia fibroblasts--a longitudinal study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11591364", "endSection": "title" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1147, "text": "Thus, the FA pathway has a novel function in ALT telomere maintenance related to DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19129235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "title" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1290, "text": "Our observations indicate that accelerated telomere shortening in patients with FA is not due to a role of FANCG at telomeres but instead may be secondary to the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15319283", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 537, "text": "Since previous works suggested an accelerated shortening of telomeres in FA, we have studied several markers of telomere integrity and function in FA patients and age-matched controls to get insights into the mechanisms and consequences of telomere erosion in FA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854176", "endSection": "abstract" } ] }, { "body": "Are Notch mutations related to T-cell Acute Lymphoblastic Leukemia (T-ALL)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21302811", "http://www.ncbi.nlm.nih.gov/pubmed/24301524", "http://www.ncbi.nlm.nih.gov/pubmed/24252593", "http://www.ncbi.nlm.nih.gov/pubmed/18056171", "http://www.ncbi.nlm.nih.gov/pubmed/23033986", "http://www.ncbi.nlm.nih.gov/pubmed/23730497", "http://www.ncbi.nlm.nih.gov/pubmed/24401270", "http://www.ncbi.nlm.nih.gov/pubmed/24140475", "http://www.ncbi.nlm.nih.gov/pubmed/21463127", "http://www.ncbi.nlm.nih.gov/pubmed/20008221", "http://www.ncbi.nlm.nih.gov/pubmed/17575125", "http://www.ncbi.nlm.nih.gov/pubmed/20015880", "http://www.ncbi.nlm.nih.gov/pubmed/16707600", "http://www.ncbi.nlm.nih.gov/pubmed/24068942", "http://www.ncbi.nlm.nih.gov/pubmed/25493453", "http://www.ncbi.nlm.nih.gov/pubmed/18184405", "http://www.ncbi.nlm.nih.gov/pubmed/20967796", "http://www.ncbi.nlm.nih.gov/pubmed/21263446", "http://www.ncbi.nlm.nih.gov/pubmed/23022380" ], "ideal_answer": [ "Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). ", "Yes, Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL).T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:5603" ], "type": "yesno", "id": "5522fadb7b523f2123000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 467, "text": "Notch receptors participate in a highly conserved signalling pathway that regulates normal development and tissue homeostasis in a context- and dose-dependent manner. Deregulated Notch signalling has been implicated in many diseases, but the clearest example of a pathogenic role is found in T-cell lymphoblastic leukaemia/lymphoma (T-LL), in which the majority of human and murine tumours have acquired mutations that lead to aberrant increases in Notch1 signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies. Recent studies reported a high incidence of gain-of-function mutations of the NOTCH1 gene in T-cell acute lymphoblastic leukemias (ALL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18184405", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1300, "text": "Our data indicate that NOTCH1 is mutated in T-ALL, but not in other common human cancers, and that NOTCH2, NOTCH3 and NOTH4 genes are rarely mutated in common human cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18184405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 602, "text": "The Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "T-cell acute lymphoblastic leukemia (T-ALL) is characterized as a high-risk stratified disease associated with frequent relapse, chemotherapy resistance, and a poorer prognostic outlook than B-precursor ALL. Many of the challenges in treating T-ALL reflect the lack of prognostic cytogenetic or molecular abnormalities on which to base therapy, including targeted therapy. Notch1 activating mutations were identified in more than 50% of T-ALL cases and can be therapeutically targeted with \u03b3-secretase inhibitors (GSIs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140475", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 296, "text": "Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 364, "text": "T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23730497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "NOTCH signaling pathway is essential in T-cell development and NOTCH1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16707600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056171", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 342, "text": "Mutations in NOTCH1/FBXW7 activate NOTCH signaling and are of prognostic significance in patients with T-cell acute lymphoblastic leukemia (T-ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25493453", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 207, "text": "Gain-of-function mutations in Notch-1 have been reported in more than 50% of human T-cell acute lymphoblastic leukemia (T-ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21302811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Notch signaling is of crucial importance in normal T-cell development and Notch 1 is frequently mutated in T-cell acute lymphoblastic leukemias (T-ALL), leading to aberrantly high Notch signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17575125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Activation of the Notch pathway occurs commonly in T acute lymphoblastic leukemia (T-ALL) because of mutations in Notch1 or Fbw7 and is involved in the regulation of cell proliferation and survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21263446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "T-cell acute lymphoblastic leukemia (T-ALL) patients frequently display NOTCH1 activating mutations and Notch can transcriptionally down-regulate the tumor suppressor PTEN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20015880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "The identification of activating mutations in NOTCH1 in over 50% of T-cell acute lymphoblastic leukemias (T-ALL) has generated major interest in the elucidation of the mechanisms of transformation downstream of oncogenic NOTCH and in the targeting of the NOTCH signaling pathway in this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20008221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "BACKGROUND: In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23033986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Activating mutations in NOTCH1 consitute the most prominent genetic abnormality in T-cell acute lymphoblastic leukemia (T-ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21463127", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24401270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The Notch signaling pathway has been recognized as a key factor for the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), because of the high incidence of activating mutations of Notch1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24301524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Notch signaling is of crucial importance in normal T-cell development and Notch 1 is frequently mutated in T-cell acute lymphoblastic leukemias (T-ALL), leading to aberrantly high Notch signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17575125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "NOTCH signaling pathway is essential in T-cell development and NOTCH1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16707600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056171", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 207, "text": "Gain-of-function mutations in Notch-1 have been reported in more than 50% of human T-cell acute lymphoblastic leukemia (T-ALL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21302811", "endSection": "abstract" } ] }, { "body": "What is the role of the Tsix gene during X chromosome inactivation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17333538", "http://www.ncbi.nlm.nih.gov/pubmed/16648248", "http://www.ncbi.nlm.nih.gov/pubmed/19013827", "http://www.ncbi.nlm.nih.gov/pubmed/21826206", "http://www.ncbi.nlm.nih.gov/pubmed/12023758" ], "ideal_answer": [ "One of the two X chromosomes in female mammalian cells is subject to inactivation (XCI) initiated by the Xist gene. Xist works as a functional RNA molecule that recruits repressive chromatin factors towards one of the female Xs for inactivation. The Tsix gene, antisense of Xist, through transcription negatively regulates Xist and protects one X-chromosome in cis from inactivation by Xist. Although, the precise molecular mechanism is still unclear it has been shown that Tsix transcription regulates the chromatin structure by altering histone tail modifications and DNA methylation at the Xist promoter. In addition, Xist and Tsix RNAs form duplexes in vivo and are processed to small RNAs, which have a potential regulatory function." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060817", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009048", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050172", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049951", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014960", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016458", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900096", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900097", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020868", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900095", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060821", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060820", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060818", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060816", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D041321", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000805", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060819" ], "type": "summary", "id": "52f1287d2059c6d71c000008", "snippets": [ { "offsetInBeginSection": 697, "offsetInEndSection": 858, "text": "A conservation of Tsix expression pattern in voles, rat and mice suggests a crucial role of the antisense transcription in regulation of Xist and XIC in rodents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21826206", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 270, "text": "the Tsix gene (antisense counterpart of Xist)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21826206", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "One of the two X chromosomes in female mammalian cells is subject to inactivation (XCI) initiated by the Xist gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21826206", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 1032, "text": "One example for antisense regulation is the Xist (X-inactive specific transcript) and Tsix gene pair, which is pivotal in X-inactivation. Xist works as a functional RNA molecule that recruits repressive chromatin factors towards one of the female Xs for inactivation. Antisense Tsix transcription negatively regulates Xist and protects one X-chromosome in cis from inactivation by Xist. Albeit, the precise molecular mechanism is still obscure it has been shown that Tsix transcription regulates the chromatin structure by altering histone tail modifications and DNA methylation at the Xist promoter. In addition, Xist and Tsix RNA form an RNA duplexes in vivo and are processed to small RNAs, which have a potential regulatory function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19013827", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 350, "text": "In eutherian mammals, random XCI of the soma requires a master regulatory locus known as the 'X-inactivation center' (XIC/Xic), wherein lies the noncoding XIST/Xist silencer RNA and its regulatory antisense Tsix gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17333538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 613, "text": "A counting process senses the X chromosome/autosome ratio and ensures that X chromosome inactivation (XCI) initiates in the early female (XX) embryo and in differentiating female ES cells but not in their male (XY) counterparts. Counting depends on the X inactivation center (Xic), which contains the Xist gene encoding a nuclear RNA, which coats the inactive X chromosome and induces gene silencing. A 37-kb sequence lying 3' to the Xist gene is known to prevent initiation of XCI in male differentiating ES cells. This region contains the major and minor promoters of the Tsix gene, which runs antisense to Xist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648248", "endSection": "abstract" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1572, "text": "Our results identify a function for DXPas34 in murine XCI and demonstrate the critical role of Tsix transcription in preventing XCI in differentiating male ES cells and in normal functioning of the counting pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 439, "text": "Transcriptional silencing of the human inactive X chromosome is induced by the XIST gene within the human X-inactivation center. The XIST allele must be turned off on one X chromosome to maintain its activity in cells of both sexes. In the mouse placenta, where X inactivation is imprinted (the paternal X chromosome is always inactive), the maternal Xist allele is repressed by a cis-acting antisense transcript, encoded by the Tsix gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12023758", "endSection": "abstract" } ] }, { "body": "Is the protein FAK (Focal Adhesion Kinase) phosphorylated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24058594", "http://www.ncbi.nlm.nih.gov/pubmed/23970932", "http://www.ncbi.nlm.nih.gov/pubmed/24157923", "http://www.ncbi.nlm.nih.gov/pubmed/24311785", "http://www.ncbi.nlm.nih.gov/pubmed/24217647", "http://www.ncbi.nlm.nih.gov/pubmed/24121272", "http://www.ncbi.nlm.nih.gov/pubmed/23817042", "http://www.ncbi.nlm.nih.gov/pubmed/24006257", "http://www.ncbi.nlm.nih.gov/pubmed/24091658", "http://www.ncbi.nlm.nih.gov/pubmed/24164869", "http://www.ncbi.nlm.nih.gov/pubmed/24115647", "http://www.ncbi.nlm.nih.gov/pubmed/23990393", "http://www.ncbi.nlm.nih.gov/pubmed/23906871" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14256646", "o": "Gene Ontology" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1150610", "o": "http://linkedlifedata.com/resource/umls/label/A2497986" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14256646", "o": "focal adhesion kinase activity" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1150610", "o": "http://linkedlifedata.com/resource/umls/label/A14256646" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2497986", "o": "FAK activity" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1150610", "o": "http://linkedlifedata.com/resource/umls/label/A2497986" } ], "ideal_answer": [ "yes, the protein FAK (Focal Adhesion Kinase) is phosphorylated." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/FAK1_HUMAN", "http://www.uniprot.org/uniprot/FAK1_CHICK", "http://www.uniprot.org/uniprot/FAK1_MOUSE", "http://www.uniprot.org/uniprot/FAK1_RAT" ], "type": "yesno", "id": "54f4c382d0d681a040000006", "snippets": [ { "offsetInBeginSection": 707, "offsetInEndSection": 792, "text": "Overexpression of NEDD9 led to tyrosine phosphorylation of FAK and SRC oncoproteins, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058594", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 130, "text": "yrosine phosphorylated FAK", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058594", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "TNF\u03b1 contributes for attenuating both Y397FAK and Y416Src phosphorylations in osteoblasts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24164869", "endSection": "title" }, { "offsetInBeginSection": 563, "offsetInEndSection": 662, "text": " It was possible to show that TNF\u03b1 provokes attenuation at Y-phosphorylation of both FAK (at Y397 )", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24164869", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 437, "text": "ownregulation of G3BP significantly inhibited the phosphorylation of Src, FAK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157923", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 590, "text": "Periodic mechanical stress significantly induced sustained phosphorylation of FAK at Tyr(397) and Tyr(576/577). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24217647", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 897, "text": "oss of \u03b1SNAP impaired Golgi-dependent glycosylation and trafficking of \u03b21 integrin and decreased phosphorylation of focal adhesion kinase (FAK) and paxillin resulting in FA disassembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311785", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 592, "text": "functional characterization of many of today's best-known Src substrates (for example, p85-Cortactin, p110-AFAP1, p130Cas, p125FAK and p120-catenin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24121272", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 607, "text": "Western blots were used for P-FAK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24115647", "endSection": "abstract" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1317, "text": "e first time, that the EGF-dependent EGFR activation led to increased P-FAKSer732", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24091658", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 1026, "text": ". P-FAKSer732 presence was crucial for the maintenance of the proliferation rate and its levels were inversely related to the levels of acetylated \u03b1-tubulin. P-FAKSer732 localized at the microtubules (MTs) of the spindle, biochemically associated with MTs and contributed to MT depolymerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24091658", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 909, "text": "specially, phosphorylation of Tyr925-FAK that is required for full activation of FAK was nearly completely suppressed even with 1nM of methyl violet 2B in A375P cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23817042", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 566, "text": " The protein expression of PTPN13, focal adhesion kinase (FAK) and phosphorylated FAK (P-FAK) was evaluated using immunohistochemical staining and western blotting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23906871", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 932, "text": "Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23970932", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 928, "text": "uppressed both the phosphorylation of FAK ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990393", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1053, "text": " A GEF-inactive Rgnef mutant rescues FAK-Y397 phosphorylation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24006257", "endSection": "abstract" } ] }, { "body": "Which is the substrate of the haspin kinase during mitosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20953165", "http://www.ncbi.nlm.nih.gov/pubmed/17084365", "http://www.ncbi.nlm.nih.gov/pubmed/19918057", "http://www.ncbi.nlm.nih.gov/pubmed/23973165", "http://www.ncbi.nlm.nih.gov/pubmed/21514157", "http://www.ncbi.nlm.nih.gov/pubmed/21447816", "http://www.ncbi.nlm.nih.gov/pubmed/20705815", "http://www.ncbi.nlm.nih.gov/pubmed/20705812", "http://www.ncbi.nlm.nih.gov/pubmed/15846065", "http://www.ncbi.nlm.nih.gov/pubmed/21749502", "http://www.ncbi.nlm.nih.gov/pubmed/15681610", "http://www.ncbi.nlm.nih.gov/pubmed/24184212", "http://www.ncbi.nlm.nih.gov/pubmed/21527018", "http://www.ncbi.nlm.nih.gov/pubmed/22335895", "http://www.ncbi.nlm.nih.gov/pubmed/21804608", "http://www.ncbi.nlm.nih.gov/pubmed/21401527", "http://www.ncbi.nlm.nih.gov/pubmed/19997740", "http://www.ncbi.nlm.nih.gov/pubmed/18978305", "http://www.ncbi.nlm.nih.gov/pubmed/23746640", "http://www.ncbi.nlm.nih.gov/pubmed/21658950", "http://www.ncbi.nlm.nih.gov/pubmed/22732840", "http://www.ncbi.nlm.nih.gov/pubmed/23071152", "http://www.ncbi.nlm.nih.gov/pubmed/23071153", "http://www.ncbi.nlm.nih.gov/pubmed/20929775" ], "ideal_answer": [ "Haspin phosphorylates histone H3 at Thr3 (H3T3ph) during mitosis" ], "exact_answer": [ "Histone 3 at Thr3" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008938", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007067", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007088", "http://www.uniprot.org/uniprot/HASP_HUMAN", "http://www.uniprot.org/uniprot/HASP_DROME" ], "type": "factoid", "id": "53442023aeec6fbd07000007", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 64, "text": "aspin phosphorylates histone H3 at Thr3 (H3T3ph) during mitosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21658950", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 742, "text": "protein kinase Haspin-mediated spreading of H3T3ph ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21514157", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 478, "text": "Haspin localizes predominantly to chromosomes and phosphorylates histone H3 at threonine-3 during mitosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19997740", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 129, "text": "haspin/Gsg2 plays an important role in mitosis, where it specifically phosphorylates Thr-3 in histone H3 (H3T3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19918057", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 88, "text": "aspin/Gsg2 is a kinase that phosphorylates histone H3 at Thr-3 (H3T3ph) during mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18978305", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 185, "text": "H3T3 phosphorylation is catalyzed by Haspin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24184212", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 92, "text": "aspin is an atypical protein kinase that in several organisms phosphorylates histone H3Thr3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23973165", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 403, "text": "histone H3 that is phosphorylated at T3 (H3T3ph) by Aurora B-stimulated Haspin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23746640", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 136, "text": "phosphorylating Thr3 of histone H3, Haspin promotes centromeric recruitment of the chromosome passenger complex (CPC) during mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071153", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 57, "text": "aspin phosphorylates histone H3 at threonine-3 (H3T3ph),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071152", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 164, "text": "Haspin-dependent histone H3 phosphorylatio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732840", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 86, "text": "aspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22335895", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 361, "text": "Haspin is a protein kinase the only known target of which is phosphorylation of histone H3 at Thr3 residue (H3T3ph)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21804608", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 418, "text": "Haspin in vitro phosphorylates histone H3 at threonine 3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749502", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 195, "text": "Haspin is a histone H3 Thr3 kinase that has important roles in chromosome cohesion during mitosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527018", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 909, "text": "phosphorylation of histone H3 threonine 3 (H3-pT3) mediated by Haspin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21447816", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 537, "text": "histone H3 specifically when it is phosphorylated at threonine 3, a mark that is placed by the mitotic kinase, haspin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21401527", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 638, "text": "H3T3 kinase haspin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20953165", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 410, "text": "phosphorylation of histone H3-threonine 3 (H3-pT3) mediated by Haspin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20929775", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 579, "text": "kinase activity of Haspin, which phosphorylates H3T3,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20705815", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 42, "text": "istone H3 Thr-3 phosphorylation by Haspin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20705812", "endSection": "title" }, { "offsetInBeginSection": 269, "offsetInEndSection": 329, "text": "phosphorylation of histone H3 threonine 3 (H3T3ph) by Haspin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20705812", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 441, "text": "Haspin/Gsg2 is a histone H3 threonine-3 kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17084365", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 573, "text": "During mitosis haspin is phosphorylated, associates with the chromosomes, centrosomes and spindle, and is responsible for phosphorylation of histone H3 at threonine-3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15846065", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 587, "text": "haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15681610", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 772, "text": "Haspin phosphorylated histone H3 at both Thr3 and Thr11 in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527018", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1475, "text": "Haspin kinase is a histone H3 threonine kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527018", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1558, "text": "Haspin phosphorylated histone H3 at both Thr3 and Thr11 in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21527018", "endSection": "abstract" } ] }, { "body": "Which are the most widely reported side-effects in the treatment of Crohn's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20458240", "http://www.ncbi.nlm.nih.gov/pubmed/3069176", "http://www.ncbi.nlm.nih.gov/pubmed/30666", "http://www.ncbi.nlm.nih.gov/pubmed/21254868", "http://www.ncbi.nlm.nih.gov/pubmed/18989561", "http://www.ncbi.nlm.nih.gov/pubmed/9005529", "http://www.ncbi.nlm.nih.gov/pubmed/11205659", "http://www.ncbi.nlm.nih.gov/pubmed/10981226", "http://www.ncbi.nlm.nih.gov/pubmed/12603508", "http://www.ncbi.nlm.nih.gov/pubmed/19420815", "http://www.ncbi.nlm.nih.gov/pubmed/17667053", "http://www.ncbi.nlm.nih.gov/pubmed/6139796", "http://www.ncbi.nlm.nih.gov/pubmed/9399771", "http://www.ncbi.nlm.nih.gov/pubmed/18469440", "http://www.ncbi.nlm.nih.gov/pubmed/21453886", "http://www.ncbi.nlm.nih.gov/pubmed/18788068", "http://www.ncbi.nlm.nih.gov/pubmed/20919963", "http://www.ncbi.nlm.nih.gov/pubmed/21317611", "http://www.ncbi.nlm.nih.gov/pubmed/17628557", "http://www.ncbi.nlm.nih.gov/pubmed/9097825", "http://www.ncbi.nlm.nih.gov/pubmed/7084615" ], "ideal_answer": [ "Leukopenia, paresthesia, psoriasis, alopecia and hemolysis are the most commonly reported side effects depending on the treatment. Severe adverse effects include myelosuppression, liver toxicity and hyperplasia, pancreatitis and pericarditis. The most severe but rare side-effects reported are progressive multifocal leukoencephalopathy (PML), serious infections, and lymphoma." ], "exact_answer": [ [ "Leukopenia" ], [ "paresthesia" ], [ "psoriasis" ], [ "alopecia" ], [ "hemolysis" ], [ "pancreatitis" ], [ "liver toxicity" ], [ "pericarditis" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8577", "http://www.disease-ontology.org/api/metadata/DOID:8778" ], "type": "list", "id": "511a20f3df1ebcce7d00000c", "snippets": [ { "offsetInBeginSection": 173, "offsetInEndSection": 266, "text": "Different cutaneous side effects have been described for anti-TNF-\u03b1 therapy such as psoriasis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21453886", "endSection": "sections.0" }, { "offsetInBeginSection": 165, "offsetInEndSection": 252, "text": "Anti-TNF drug-induced alopecia is a less well-known side effect of this class of drugs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21317611", "endSection": "sections.0" }, { "offsetInBeginSection": 432, "offsetInEndSection": 471, "text": "3 patients who developed scalp alopecia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21317611", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Psoriasis and psoriatic arthritis induced in a patient treated with infliximab for Crohn's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21254868", "endSection": "title" }, { "offsetInBeginSection": 220, "offsetInEndSection": 322, "text": "side effects appearing in about a fifth of the patients, including myelosuppression and liver toxicity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20919963", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Persistent corneal endothelial deposits associated with rifabutin therapy for Crohn's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20458240", "endSection": "title" }, { "offsetInBeginSection": 93, "offsetInEndSection": 204, "text": "complained of alopecia 3 days after starting 6-mercaptopurine (6-MP) and then developed severe myelosuppression", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19420815", "endSection": "sections.0" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1042, "text": "Leucopoenia was the more frequent side effect observed, occurring in 36 (34%)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989561", "endSection": "sections.0" }, { "offsetInBeginSection": 766, "offsetInEndSection": 820, "text": "Nausea, vomit, although slight, occurred in 29 (27.4%)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989561", "endSection": "sections.0" }, { "offsetInBeginSection": 1, "offsetInEndSection": 100, "text": "Nodular regenerative hyperplasia as a side effect of azathioprine in a patient with Crohn's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18788068", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 253, "text": "The whole blood count revealed a pancytopenia, hyperbilirubinemia and slightly elevated transaminases", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18788068", "endSection": "sections.0" }, { "offsetInBeginSection": 465, "offsetInEndSection": 579, "text": "Analysis of the liver histology was highly suggestive of an azathioprine-related, nodular regenerative hyperplasia", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18788068", "endSection": "sections.0" }, { "offsetInBeginSection": 725, "offsetInEndSection": 882, "text": "3 serious adverse events (SAEs) known to be associated with CD treatment (progressive multifocal leukoencephalopathy (PML), serious infections, and lymphoma)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17628557", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Severe pulmonary toxicity after azathioprine/6-mercaptopurine initiation for the treatment of inflammatory bowel disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17667053", "endSection": "title" }, { "offsetInBeginSection": 81, "offsetInEndSection": 162, "text": "A severe side effect is acute pancreatitis, which is specific for Crohn's disease", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18469440", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Recurrent myopericarditis in association with Crohn's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12603508", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Interstitial nephritis in patients with inflammatory bowel disease treated with mesalamine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11205659", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 86, "text": "Pancreatitis in a patient with Crohn disease treated with mesalazine and azathioprine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10981226", "endSection": "title" }, { "offsetInBeginSection": 174, "offsetInEndSection": 303, "text": "Leukopenia and thrombocytopenia are observed mostly as a side effect of therapy, particularly with use of immunosuppressive drugs", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9399771", "endSection": "sections.0" }, { "offsetInBeginSection": 305, "offsetInEndSection": 403, "text": "Immune thrombocytopenic purpura is rarely reported in association with inflammatory bowel disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9399771", "endSection": "sections.0" }, { "offsetInBeginSection": 500, "offsetInEndSection": 546, "text": "resulted to watery stools, vomiting, and fever", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9097825", "endSection": "sections.0" }, { "offsetInBeginSection": 640, "offsetInEndSection": 730, "text": "Eosionophilia was present and the lymphocyte stimulation test with mesalazine was positive", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9097825", "endSection": "sections.0" }, { "offsetInBeginSection": 149, "offsetInEndSection": 228, "text": "Pericarditis as a side effect induced by sulfasalazine or 5-aminosalicylic acid", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9005529", "endSection": "sections.0" }, { "offsetInBeginSection": 483, "offsetInEndSection": 602, "text": "The commonest side-effect was hyperaesthesia, but one patient developed nephrotoxicity and one developed hepatotoxicity", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3069176", "endSection": "sections.0" }, { "offsetInBeginSection": 336, "offsetInEndSection": 437, "text": "The only troublesome side effect is paresthesia, which apparently is dose-related and not progressive", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6139796", "endSection": "sections.0" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1223, "text": "The only major side effect observed was paresthesias. These occurred in 50% of the patients and developed in the patients at a mean of 6.5 mo after the onset of treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7084615", "endSection": "sections.0" }, { "offsetInBeginSection": 690, "offsetInEndSection": 750, "text": "Hemolysis is not a rare side-effect of sulfasalazine therapy", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30666", "endSection": "sections.0" }, { "offsetInBeginSection": 79, "offsetInEndSection": 226, "text": "17 of 40 (43%) patients with inflammatory bowel disease receiving sulfasalazine had evidence of hemolysis as detected by starch gel electrophoresis", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30666", "endSection": "sections.0" } ] }, { "body": "Are most driver gene mutations synonymous or non-synonymous?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22072984", "http://www.ncbi.nlm.nih.gov/pubmed/23799614", "http://www.ncbi.nlm.nih.gov/pubmed/15946860", "http://www.ncbi.nlm.nih.gov/pubmed/23819581", "http://www.ncbi.nlm.nih.gov/pubmed/19633228", "http://www.ncbi.nlm.nih.gov/pubmed/23015295", "http://www.ncbi.nlm.nih.gov/pubmed/23450047", "http://www.ncbi.nlm.nih.gov/pubmed/24147068", "http://www.ncbi.nlm.nih.gov/pubmed/23935863", "http://www.ncbi.nlm.nih.gov/pubmed/23704925", "http://www.ncbi.nlm.nih.gov/pubmed/23694700", "http://www.ncbi.nlm.nih.gov/pubmed/22649506", "http://www.ncbi.nlm.nih.gov/pubmed/22893128" ], "ideal_answer": [ "A common goal of tumor sequencing projects is finding genes whose mutations are selected for during tumor development. This is accomplished by choosing genes that have more non-synonymous mutations than expected from an estimated background mutation frequency. ", "A common goal of tumor sequencing projects is finding genes whose mutations are selected for during tumor development. This is accomplished by choosing genes that have more non-synonymous mutations than expected from an estimated background mutation frequency." ], "exact_answer": [ "non-synonymous" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "factoid", "id": "534427f8aeec6fbd07000009", "snippets": [ { "offsetInBeginSection": 1649, "offsetInEndSection": 1869, "text": "Therefore, this study highlights the need for multiple biopsies and sequencing during progression of a cancer and combinatorial DNA and RNA sequencing approach for systematic identification of expressed driver mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24147068", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 934, "text": "Whole genome sequencing of the index liver metastasis identified 44 non-synonymous somatic mutations in 42 genes (0.85 mutation/MB) and a large hemizygous deletion in the ATRX gene which has been recently reported in neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24147068", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 650, "text": "In addition, we show that NetDiseaseSNP discriminates cancer driver and passenger mutations satisfactorily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23935863", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 913, "text": "Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23935863", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1704, "text": "Moreover, we find that a large fraction of the driver mutations are neither located in conserved functional sites, nor responsible for structural stability, but rather regulate protein activity through allosteric transitions, protein-protein interactions, or protein-nucleic acid interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23819581", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 239, "text": "We used whole-exome sequencing to identify novel non-synonymous somatic mutations in squamous cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23799614", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 399, "text": "We identified 101 single-nucleotide variants (SNVs) including 77 non-synonymous SNVs (67 missense and 10 nonsense mutations) and 11 INDELs causing frameshifts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23799614", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 1066, "text": "Besides confirming the presence of known melanoma driver mutations (BRAF(V600E), NRAS(Q61R) ), we identified novel mutated genes involved in signalling pathways crucial for melanoma pathogenesis and already addressed by current targeted therapies (such as MAPK and glutamate pathways).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "A common goal of tumor sequencing projects is finding genes whose mutations are selected for during tumor development. This is accomplished by choosing genes that have more non-synonymous mutations than expected from an estimated background mutation frequency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23694700", "endSection": "abstract" } ] }, { "body": "What is the advantage of neutral loss detection in phosphoproteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21455477", "http://www.ncbi.nlm.nih.gov/pubmed/16641100", "http://www.ncbi.nlm.nih.gov/pubmed/18785766", "http://www.ncbi.nlm.nih.gov/pubmed/21526838", "http://www.ncbi.nlm.nih.gov/pubmed/15665377", "http://www.ncbi.nlm.nih.gov/pubmed/19241031", "http://www.ncbi.nlm.nih.gov/pubmed/22844594", "http://www.ncbi.nlm.nih.gov/pubmed/19056867", "http://www.ncbi.nlm.nih.gov/pubmed/19504542", "http://www.ncbi.nlm.nih.gov/pubmed/23918812", "http://www.ncbi.nlm.nih.gov/pubmed/21033674" ], "ideal_answer": [ "The localization of phosphorylation sites in peptide sequences is a challenging problem in large-scale phosphoproteomics analysis. The intense neutral loss peaks and the coexistence of multiple serine/threonine and/or tyrosine residues are limiting factors for objectively scoring site patterns across thousands of peptides.\nCID of phosphopeptides typically results in spectra dominated by a neutral loss of the phosphate group allowing detection and sequencing of phosphopeptides." ], "type": "summary", "id": "550889db098a1b487b000005", "snippets": [ { "offsetInBeginSection": 809, "offsetInEndSection": 927, "text": "The higher-order fragmentations of neutral loss ions enhance the fragment ion mass spectra of phosphorylated peptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844594", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1428, "text": "we identified a novel fragmentation mechanism that generates a phosphorylation site-specific neutral loss derived x-ion, which directly pinpoints the phosphorylated residue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21526838", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 624, "text": "CID of phosphopeptides typically results in spectra dominated by a neutral loss of the phosphate group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19504542", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1143, "text": "In this procedure we use a combination of tools to assign b-, y-, neutral loss, and internal fragment ions, with the goal of assigning all significant ions in the MS/MS spectrum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19241031", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 777, "text": "We extended the proteomic analysis to phosphoproteomic profiling using neutral loss scanning, and this yielded multiple novel phosphorylation sites, including serine-811 in the thiazide-sensitive Na-Cl co-transporter, NCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19056867", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1025, "text": "LC separation and MS/MS are followed by neutral loss-dependent MS/MS/MS for phosphopeptide identification using a linear ion trap (LTQ)-FT mass spectrometer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18785766", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 566, "text": "phosphorylation site identification by liquid chromatography-mass spectrometry(n) neutral loss scanning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16641100", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1500, "text": "MS/MS and neutral loss-directed MS/MS/MS analysis allowed detection and sequencing of phosphopeptides with exceptional accuracy and specificity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15665377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "The localization of phosphorylation sites in peptide sequences is a challenging problem in large-scale phosphoproteomics analysis. The intense neutral loss peaks and the coexistence of multiple serine/threonine and/or tyrosine residues are limiting factors for objectively scoring site patterns across thousands of peptides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23918812", "endSection": "abstract" } ] }, { "body": "Does ghrelin play a role in ischemic stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19352052", "http://www.ncbi.nlm.nih.gov/pubmed/23576609", "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "http://www.ncbi.nlm.nih.gov/pubmed/24961317", "http://www.ncbi.nlm.nih.gov/pubmed/24768795", "http://www.ncbi.nlm.nih.gov/pubmed/20720512", "http://www.ncbi.nlm.nih.gov/pubmed/22190447", "http://www.ncbi.nlm.nih.gov/pubmed/15613277" ], "ideal_answer": [ "Yes. It has been shown that serum ghrelin levels are reduced after ischemic stroke and ghrelin is associated with stroke type. Ghrelin can be a useful marker for the prediction of stoke after cardiopulmonary bypass. Ghrelin may be neuroprotective after injury in animal models of cerebral ischemia by inhibiting apoptotic processes, inflammation, nNOS activity and modulating gastrointestinal motility." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/GHRL_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054439" ], "type": "yesno", "id": "551c2c276b348bb82c00000c", "snippets": [ { "offsetInBeginSection": 96, "offsetInEndSection": 213, "text": "Recent evidence suggests that ghrelin may also be neuroprotective after injury in animal models of cerebral ischemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576609", "endSection": "abstract" }, { "offsetInBeginSection": 1573, "offsetInEndSection": 1840, "text": "Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576609", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1084, "text": " The serum ghrelin level was higher in the MCAO group when compared with the control group (P < 0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190447", "endSection": "abstract" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1587, "text": "Our results showed that higher level of serum ghrelin decreased gastrointestinal motility and damage to the intestinal mucosa existed in rats with MCAO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Leptin, adiponectin and ghrelin, new potential mediators of ischemic stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "endSection": "title" }, { "offsetInBeginSection": 597, "offsetInEndSection": 723, "text": "RESULTS: Significantly higher levels of leptin and lower levels of adiponectin and ghrelin were confirmed in the stroke group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 983, "text": "Ghrelin levels correlated mildly with triglyceride levels, and were dominant in men with cardioembolic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1291, "text": "CONCLUSIONS: Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Ghrelin suppresses inflammation and neuronal nitric oxide synthase in focal cerebral ischemia via the vagus nerve.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720512", "endSection": "title" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1026, "text": "Compared with vehicle treatment, human ghrelin treatment in vagus nerve-intact rats after MCAO showed marked reduction in neurological deficit by 57% and infarct size by 25%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720512", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1498, "text": "Human ghrelin treatment in vagus nerve-intact rats significantly decreased the above measurements. Human ghrelin treatment also improved 7-day survival and significantly decreased neurological deficit over the entire 7 days after MCAO in vagus nerve-intact rats compared with vehicle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720512", "endSection": "abstract" }, { "offsetInBeginSection": 1671, "offsetInEndSection": 1825, "text": "Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Ghrelin is known to promote neuronal defense and survival against ischemic injury by inhibiting apoptotic processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352052", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1104, "text": "Our data indicate that des-acyl ghrelin, as well as ghrelin, protect cortical neurons against ischemic injury through the inhibition of Par-4 expression and apoptotic molecules in mitochondrial pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352052", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1083, "text": "In conclusion, it is considered that ghrelin as well as S-100B can be a useful marker for the prediction of stoke after CPB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15613277", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1237, "text": "Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 311, "text": "In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24961317", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 450, "text": "Both ghrelin and des-acyl ghrelin protected cortical neurons from ischemic injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352052", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1098, "text": "Our data indicate that des-acyl ghrelin, as well as ghrelin, protect cortical neurons against ischemic injury through the inhibition of Par-4 expression and apoptotic molecules in mitochondrial pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 310, "text": "In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24961317", "endSection": "abstract" }, { "offsetInBeginSection": 1672, "offsetInEndSection": 1825, "text": "Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20720512", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 450, "text": "Both ghrelin and des-acyl ghrelin protected cortical neurons from ischemic injury", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352052", "endSection": "abstract" }, { "offsetInBeginSection": 1572, "offsetInEndSection": 1838, "text": "Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576609", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 367, "text": "In the present study, we investigated the role of prostate apoptosis response-4 (Par-4), a proapoptotic gene the expression of which is increased after ischemic injury, in ghrelin-mediated neuroprotection during middle cerebral artery occlusion (MCAO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352052", "endSection": "abstract" }, { "offsetInBeginSection": 1106, "offsetInEndSection": 1250, "text": "Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22167137", "endSection": "abstract" } ] }, { "body": "What is the mechanism of drug-induced gingival overgrowth?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16712728", "http://www.ncbi.nlm.nih.gov/pubmed/8233439", "http://www.ncbi.nlm.nih.gov/pubmed/15221438", "http://www.ncbi.nlm.nih.gov/pubmed/23878564", "http://www.ncbi.nlm.nih.gov/pubmed/16006738", "http://www.ncbi.nlm.nih.gov/pubmed/12466121", "http://www.ncbi.nlm.nih.gov/pubmed/11453236" ], "ideal_answer": [ "Drug-induced gingival overgrowth (GO) is a frequent and adverse side-effect associated principally with the administration of the immunosuppressive drug cyclosporin A (CsA) and also certain anti-epileptic and anti-hypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and the accumulation of excessive amounts of connective tissue. Keratinocyte growth factor (KGF), which is a potent epithelial cell mitogen that has been implicated in other hyperplastic conditions could be involved in the molecular pathology of GO. Also, since cathepsin-L deficiency was reported to be associated with thickening of the skin, impaired cathepsin-L activity may play a key role in the establishment of skin and gingival abnormalities seen in I-cell disease. In addition, reduced cathepsin-L activity may play an important role in inducing drug-induced gingival overgrowth. Furthermore, the enhanced proliferation of gingival fibroblasts observed in this disease could be caused at least partly by the effects of the drugs on the cell cycle and cyclin expression in these cells. The increase in cell growth that occurs in drug-induced gingival overgrowth may be mediated by over-expression of cyclin B1." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3086", "http://www.disease-ontology.org/api/metadata/DOID:3087" ], "type": "summary", "id": "554500065beec11c1000000b", "snippets": [ { "offsetInBeginSection": 1886, "offsetInEndSection": 1984, "text": "The results indicated that CsA stimulated cell proliferation in the pediatric fibroblast cell line", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23878564", "endSection": "abstract" }, { "offsetInBeginSection": 2341, "offsetInEndSection": 2552, "text": "The mechanism of a CsA-induced fibroblast overgrowth may converge on the steps involving fibroblast proliferation and cytokine network including IL-6, IL-8, IL-1\u03b2, TGF-\u03b21, and PGE2, in both adults and pediatrics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23878564", "endSection": "abstract" }, { "offsetInBeginSection": 1985, "offsetInEndSection": 2326, "text": " Comparison between the results in the adult and pediatric groups demonstrated that the levels of IL-1\u03b2, IL-6, IL-8, and PGE2 were significantly higher in the pediatric group than in the adult group; however, statistics showed no significant difference in the levels of TNF-\u03b1 and TGF-\u03b21 and CsA-induced proliferation between these two groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23878564", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 218, "text": "Drug-induced gingival overgrowth is a frequent adverse effect associated principally with administration of the immunosuppressive drug cyclosporin A and also certain antiepileptic and antihypertensive drugs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16712728", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1393, "text": "The results suggest that the increased epithelial thickness observed in Cyclosporin A-induced gingival overgrowth is associated with increased proliferative activity in keratinocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16712728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "It is well-known that the anticonvulsant drug, phenytoin (PHT), induces gingival overgrowth as a side effect. The mechanism of PHT-induced gingival overgrowth, however, is not well understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Gingival overgrowth is a frequent and adverse side-effect caused by certain immunosuppressant, anti-convulsant and calcium channel-blocking drugs. Although the precise mechanism is not yet known, the enhanced proliferation of gingival fibroblasts observed in this disease could be caused at least partly by the effects of the drugs on the cell cycle and cyclin expression in these cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15221438", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 916, "text": "Thus, the increase in cell growth that occurs in drug-induced gingival overgrowth may be mediated by over-expression of cyclin B1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15221438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The immunosuppressant and hyperplasia-inducing drug cyclosporin A regulates the cell cycle and cyclin B1 gene expression in gingival fibroblasts in vitro", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15221438", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12466121", "endSection": "title" }, { "offsetInBeginSection": 566, "offsetInEndSection": 726, "text": "A calcium antagonist, nifedipine, specifically suppressed cathepsin-L activity and mRNA expression, but not that of cathepsin-B in cultured gingival fibroblasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12466121", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1588, "text": "Since cathepsin-L deficiency was reported to be associated with thickening of the skin, impaired cathepsin-L activity may play a key role in the establishment of skin and gingival abnormalities seen in I-cell disease. In addition, reduced cathepsin-L activity may play an important role in inducing drug-induced gingival overgrowth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12466121", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 390, "text": "Drug-induced gingival overgrowth (GO) is a frequent and adverse side-effect associated principally with the administration of the immunosuppressive drug cyclosporin A (CsA) and also certain anti-epileptic and anti-hypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and the accumulation of excessive amounts of connective tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11453236", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 701, "text": "Although the mechanism by which the drugs cause GO is not yet understood, keratinocyte growth factor (KGF), which is a potent epithelial cell mitogen, has been implicated in other hyperplastic conditions, including mammary and prostatic hyperplasia, and could also be involved in the molecular pathology of GO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11453236", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1637, "text": "This study has shown, for the first time, that the level of KGF is elevated in GO and suggests that KGF may have an important role in the enhanced epithelial proliferation associated with GO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11453236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Certain anticonvulsants, cyclosporine, and a variety of calcium channel blockers have been shown to produce clinically and histologically similar gingival enlargements in certain susceptible patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8233439", "endSection": "abstract" } ] }, { "body": "Is LPS a microbial product?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25957290", "http://www.ncbi.nlm.nih.gov/pubmed/18406367", "http://www.ncbi.nlm.nih.gov/pubmed/26029695", "http://www.ncbi.nlm.nih.gov/pubmed/25259707" ], "ideal_answer": [ "Yes, the lipopolysaccharide (LPS) is a component of the bacterial cell wall." ], "exact_answer": "yes", "type": "yesno", "id": "56e6f419a12c1fc13b000002", "snippets": [ { "offsetInBeginSection": 237, "offsetInEndSection": 321, "text": "and microbial translocation [lipopolysaccaride (LPS), microbial 16S rDNA and sCD14] ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25259707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18406367", "endSection": "title" }, { "offsetInBeginSection": 793, "offsetInEndSection": 827, "text": "bacterial lipopolysaccharide (LPS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029695", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 327, "text": "sterile bacterial wall lipopolysaccharide (LPS) to investigate the changes in innate lung microbiota", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25957290", "endSection": "abstract" } ] }, { "body": "Which cyclin- dependent kinase inhibitor is regulated by Bmi-1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19390085", "http://www.ncbi.nlm.nih.gov/pubmed/17989730", "http://www.ncbi.nlm.nih.gov/pubmed/18275833", "http://www.ncbi.nlm.nih.gov/pubmed/17102614", "http://www.ncbi.nlm.nih.gov/pubmed/17651940", "http://www.ncbi.nlm.nih.gov/pubmed/21496667", "http://www.ncbi.nlm.nih.gov/pubmed/19321450", "http://www.ncbi.nlm.nih.gov/pubmed/9923679", "http://www.ncbi.nlm.nih.gov/pubmed/11355949", "http://www.ncbi.nlm.nih.gov/pubmed/15892997", "http://www.ncbi.nlm.nih.gov/pubmed/20551323", "http://www.ncbi.nlm.nih.gov/pubmed/18371338", "http://www.ncbi.nlm.nih.gov/pubmed/20661663", "http://www.ncbi.nlm.nih.gov/pubmed/21928107", "http://www.ncbi.nlm.nih.gov/pubmed/16869752", "http://www.ncbi.nlm.nih.gov/pubmed/18346113", "http://www.ncbi.nlm.nih.gov/pubmed/16778197", "http://www.ncbi.nlm.nih.gov/pubmed/17597110", "http://www.ncbi.nlm.nih.gov/pubmed/14982841", "http://www.ncbi.nlm.nih.gov/pubmed/15964994", "http://www.ncbi.nlm.nih.gov/pubmed/20591222", "http://www.ncbi.nlm.nih.gov/pubmed/21164364", "http://www.ncbi.nlm.nih.gov/pubmed/17233832", "http://www.ncbi.nlm.nih.gov/pubmed/19389366", "http://www.ncbi.nlm.nih.gov/pubmed/14536079", "http://www.ncbi.nlm.nih.gov/pubmed/14574365", "http://www.ncbi.nlm.nih.gov/pubmed/14732230", "http://www.ncbi.nlm.nih.gov/pubmed/16537449", "http://www.ncbi.nlm.nih.gov/pubmed/17145810", "http://www.ncbi.nlm.nih.gov/pubmed/16155021", "http://www.ncbi.nlm.nih.gov/pubmed/12482990", "http://www.ncbi.nlm.nih.gov/pubmed/12714971", "http://www.ncbi.nlm.nih.gov/pubmed/19907431", "http://www.ncbi.nlm.nih.gov/pubmed/16157028", "http://www.ncbi.nlm.nih.gov/pubmed/18371328" ], "ideal_answer": [ "p16INK4 (also known as CDKN2A)" ], "exact_answer": [ "p16INK4" ], "concepts": [ "http://www.uniprot.org/uniprot/CD2A1_MONDO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019941", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045736", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050756" ], "type": "factoid", "id": "533abc76d6d3ac6a34000064", "snippets": [ { "offsetInBeginSection": 663, "offsetInEndSection": 748, "text": "the knockdown of BMI-1 expression could lead to significant up-regulation of p16INK4a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20661663", "endSection": "abstract" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1694, "text": "In EC9706 cells transfected by Bmi-1 siRNA, the expression levels of p16 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20591222", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 392, "text": "One important pathway regulated by Bmi-1 is that involving two cyclin-dependent kinase inhibitors, p16(Ink4a) and p19(Arf)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20551323", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 814, "text": "We also observe that ROS-induced up-regulation of p16(Ink4a) occurs correlatively with ERK1/2-dependent down-regulation and subsequent dissociation from chromatin of Bmi-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19321450", "endSection": "abstract" }, { "offsetInBeginSection": 51, "offsetInEndSection": 214, "text": "Bmi-1 is important for postnatal, but not embryonic, neural stem cell (NSC) self-renewal and have identified the cell-cycle inhibitors p16/p19 as molecular targets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371338", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 307, "text": "Bmi-1 function in stem cells during development that, surprisingly, seems to involve regulation of the cell-cycle inhibitor p21", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371328", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 892, "text": "Our data therefore implicate p21 as an important Bmi-1 target in NSCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18371338", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 663, "text": "Bmi-1-mediated repression of Cdkn2A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18275833", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 894, "text": "decreased expression of proliferating cell nuclear antigen and Bmi-1; upregulation of p16(INK4a)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17989730", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 701, "text": "BMI-1 promotes self-renewal of stem cells largely by interfering with two central cellular tumor suppressor pathways, p16(Ink4a)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17651940", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 327, "text": "p16INK4a and p14ARF tumor suppressors, human telomerase reverse transcriptase (h-TERT), and oncoprotein c-Myc have been implicated in the regulation of the cell cycle and proliferation mediated by PcG proteins, mainly Bmi-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17145810", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 492, "text": "involving the polycomb group repressor Bmi-1 and the cyclin-dependent kinase inhibitor p16(INK4a)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17102614", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 596, "text": "increased frequency to a telomere-independent senescent state mediated by the cyclin-dependent kinase inhibitor p16(INK4a). p16(INK4a) expression was regulated by the Polycomb group repressor Bmi-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16537449", "endSection": "abstract" }, { "offsetInBeginSection": 1445, "offsetInEndSection": 1549, "text": "The antisense Bmi-1 gene can inhibit the growth of K562 cell and upgrade expression of p16 in K562 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16157028", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 989, "text": "overexpression of BMI-1, a transcriptional repressor of the p16(INK4a) locus,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16155021", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 874, "text": "experimental model systems indicate that p16 is a downstream target of Bmi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14982841", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 777, "text": "In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14574365", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 935, "text": "A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12714971", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 106, "text": "polycomb protein Bmi-1 represses the INK4a locus, which encodes the tumor suppressors p16 and p14(ARF)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12482990", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 110, "text": "Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9923679", "endSection": "title" }, { "offsetInBeginSection": 777, "offsetInEndSection": 912, "text": "in bmi-1-deficient lymphocytes, the expression of the tumour suppressors p16 and p19Arf, which are encoded by ink4a, is raised markedly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9923679", "endSection": "abstract" }, { "offsetInBeginSection": 1493, "offsetInEndSection": 1526, "text": "BMI-1-mediated INK4a/ARF pathway ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21928107", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 320, "text": " expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18346113", "endSection": "abstract" }, { "offsetInBeginSection": 905, "offsetInEndSection": 1029, "text": "reduced expression of Bmi-1, OC, DSP, and BSP compared with rapidly proliferating cells, whereas p16(INK4A) level increased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21496667", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 52, "text": "16Ink4a suppression of lung adenocarcinoma by Bmi-1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21164364", "endSection": "title" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1460, "text": "The suppression of p16Ink4a occurred in parallel with an increase in Bmi-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21164364", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1282, "text": "Bmi-1 overexpression reduced p16(INK4a) promoter activity ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19907431", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 35, "text": "mi-1 regulates the Ink4a/Arf locus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19390085", "endSection": "title" }, { "offsetInBeginSection": 212, "offsetInEndSection": 291, "text": "derepression of the Ink4a/Arf locus is associated with decreased Bmi-1 binding,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19390085", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1152, "text": "pronounced effects of Bmi-1 over-expression in culture were largely attributable to the attenuated induction of p16(Ink4a) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19389366", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 443, "text": "BMI-1 is a transcriptional repressor of the Ink4a/Arf locus encoding p16(ink4a)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17597110", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 442, "text": "introduction of Bmi-1 can inhibit p16(INK4a) expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17233832", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 718, "text": "Bmi-1 promotes stem cell self-renewal partly by repressing the expression of Ink4a ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16869752", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1060, "text": "Overexpression of Bmi-1 in NPECs led to the induction of human telomerase reverse transcriptase activity and reduction of p16(INK4a) expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16778197", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 742, "text": "Bmi-1 thus prevents the premature senescence of neural stem cells by repressing Ink4a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15964994", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 442, "text": "overexpression of the polycomb-group gene BMI-1 might also down-regulate p16 expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15892997", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 113, "text": "Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14732230", "endSection": "title" }, { "offsetInBeginSection": 809, "offsetInEndSection": 925, "text": "modulation of Bmi-1 protein might be involved in human colorectal carcinogenesis by repressing the INK4a/ARF protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14732230", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 29, "text": "mi-1 regulation of INK4A-ARF", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14536079", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 428, "text": "expression of BMI-1, a lymphoid oncogene whose product functions as a transcriptional repressor of the INK4A-ARF tumor suppressor locu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14536079", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 126, "text": "bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11355949", "endSection": "title" }, { "offsetInBeginSection": 419, "offsetInEndSection": 495, "text": "bmi-1 overexpression induces immortalization due to repression of p16/p19ARF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11355949", "endSection": "abstract" } ] }, { "body": "Which microRNAs are involved in exercise adaptation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19440340", "http://www.ncbi.nlm.nih.gov/pubmed/21690193", "http://www.ncbi.nlm.nih.gov/pubmed/23242657", "http://www.ncbi.nlm.nih.gov/pubmed/23047984", "http://www.ncbi.nlm.nih.gov/pubmed/21311168", "http://www.ncbi.nlm.nih.gov/pubmed/20724368" ], "ideal_answer": [ "miR-1, miR-133, miR-208a, miR-206, miR-494, miR-146a, miR-222, miR-21, miR-221, miR-20a, miR-133a, miR-133b, miR-23, miR-107 and miR-181 are involved in exercise adaptation" ], "exact_answer": [ [ "miR-1" ], [ "miR-133" ], [ "miR-208a" ], [ "miR-206" ], [ "miR-494" ], [ "miR-146a" ], [ "miR-222" ], [ "miR-21" ], [ "miR-221" ], [ "miR-20a" ], [ "miR-133a" ], [ "miR-133b" ], [ "miR-23" ], [ "miR-107" ], [ "miR-181" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005081", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000222", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000220", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "list", "id": "518cca6f310faafe0800000a", "snippets": [ { "offsetInBeginSection": 345, "offsetInEndSection": 614, "text": "Some miRNAs as miR-1, miR-133 and miR-208a are highly expressed in the heart and strongly associated with the development of cardiac hypertrophy. Recent data indicate that these miRNAs as well as miR-206 change their expression quickly in response to physical activity.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242657", "endSection": "sections.0" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1253, "text": "the miR-494 content significantly decreased after endurance exercise in C57BL/6J mice, accompanied by an increase in expression of mtTFA and Foxj3 proteins. These results suggest that miR-494 regulates mitochondrial biogenesis by downregulating mtTFA and Foxj3 during myocyte differentiation and skeletal muscle adaptation to physical exercise.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23047984", "endSection": "sections.0" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1268, "text": "1) c-miRNA up-regulated by acute exercise before and after sustained training (miR-146a and miR-222), (2) c-miRNA responsive to acute exercise before but not after sustained training (miR-21 and miR-221), (3) c-miRNA responsive only to sustained training (miR-20a),", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21690193", "endSection": "sections.0" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1416, "text": "MicroRNA 1 expression was decreased independent of the training modality, and was paralleled by an increased expression of IGF-1 representing a potential target.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21311168", "endSection": "sections.0" }, { "offsetInBeginSection": 169, "offsetInEndSection": 476, "text": "we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus lateralis of healthy young males (n = 10) in relation to a hyperinsulinaemic\u2013euglycaemic clamp as well as acute endurance exercise before and after 12 weeks of endurance training.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20724368", "endSection": "sections.0" }, { "offsetInBeginSection": 824, "offsetInEndSection": 934, "text": "In resting biopsies, endurance training for 12 weeks decreased basal expression of all four myomiRs (P < 0.05)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20724368", "endSection": "sections.0" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1253, "text": "These results suggest that miR-494 regulates mitochondrial biogenesis by downregulating mtTFA and Foxj3 during myocyte differentiation and skeletal muscle adaptation to physical exercise.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23047984", "endSection": "sections.0" } ] }, { "body": "Has field-programmable gate array (FPGA) technology been used to solve sequence alignment problems?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21724593", "http://www.ncbi.nlm.nih.gov/pubmed/17555593", "http://www.ncbi.nlm.nih.gov/pubmed/18048180", "http://www.ncbi.nlm.nih.gov/pubmed/17946720", "http://www.ncbi.nlm.nih.gov/pubmed/22151470", "http://www.ncbi.nlm.nih.gov/pubmed/18798993", "http://www.ncbi.nlm.nih.gov/pubmed/16342039", "http://www.ncbi.nlm.nih.gov/pubmed/15919726", "http://www.ncbi.nlm.nih.gov/pubmed/18412963", "http://www.ncbi.nlm.nih.gov/pubmed/19273034", "http://www.ncbi.nlm.nih.gov/pubmed/19208138", "http://www.ncbi.nlm.nih.gov/pubmed/19492068", "http://www.ncbi.nlm.nih.gov/pubmed/8481828" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0021572", "o": "Alignments, Sequence" } ], "ideal_answer": [ "Yes. Field-Programmable Gate Arrays (FPGAs) are reconfigurable computing platforms that have found several applications in diverse domains, including digital signal processing, medical imaging and bioinformatics. Specific applications of FPGAs for biological sequence alignment have been reported for dynamic programming-based pairwise (local or global) sequence alignment, progressive multiple sequence alignment, profile alignment, Burrows-Wheeler transform (BWT) based alignment, heuristic pairwise alignment." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017421", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017423", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017385", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012689", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017386", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003201", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016415", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020539" ], "type": "yesno", "id": "51be1750047fa84d1d000005", "snippets": [ { "offsetInBeginSection": 868, "offsetInEndSection": 1262, "text": "A linear error model for the raw intensity data and Burrows-Wheeler transform (BWT) based alignment are combined utilizing a Bayesian score function, which is then globally optimized over all possible genomic locations using an efficient branch-and-bound approach. The algorithm has been implemented in soft- and hardware [field-programmable gate array (FPGA)] to achieve real-time performance.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21724593", "endSection": "sections.0" }, { "offsetInBeginSection": 383, "offsetInEndSection": 800, "text": "we have designed and built a high-performance FPGA-accelerated version of BLASTP, Mercury BLASTP. In this paper, we describe the architecture of the portions of the application that are accelerated in the FPGA, and we also describe the integration of these FPGA-accelerated portions with the existing BLASTP software. We have implemented Mercury BLASTP on a commodity workstation with two Xilinx Virtex-II 6000 FPGAs.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19492068", "endSection": "sections.0" }, { "offsetInBeginSection": 576, "offsetInEndSection": 889, "text": "This paper shows how reconfigurable architectures can be used to derive an efficient fine-grained parallelization of the dynamic programming calculation. We describe how this technique leads to significant runtime savings for HMM database scanning on a standard off-the-shelf field-programmable gate array (FPGA).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19273034", "endSection": "sections.0" }, { "offsetInBeginSection": 442, "offsetInEndSection": 650, "text": "We have constructed a linear systolic array to perform pairwise sequence distance computations using dynamic programming. This results in an implementation with significant runtime savings on a standard FPGA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18048180", "endSection": "sections.0" }, { "offsetInBeginSection": 284, "offsetInEndSection": 459, "text": "in this paper, we focused on accelerating the Smith-Waterman algorithm by modifying the computationally repeated portion of the algorithm by FPGA hardware custom instructions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17946720", "endSection": "sections.0" }, { "offsetInBeginSection": 286, "offsetInEndSection": 839, "text": "We present a reconfigurable systolic architecture that can be applied for the efficient treatment of several dynamic programming methods for resolving well-known problems, such as global and local sequence alignment, approximate string matching and longest common subsequence. The dynamicity of the reconfigurability was found to be useful for practical applications in the construction of sequence alignments. A VHDL (VHSIC hardware description language) version of this new architecture was implemented on an APEX FPGA (Field programmable gate array).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16342039", "endSection": "sections.0" }, { "offsetInBeginSection": 256, "offsetInEndSection": 368, "text": "This results in an implementation of ClustalW with significant runtime savings on a standard off-the-shelf FPGA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15919726", "endSection": "sections.0" }, { "offsetInBeginSection": 597, "offsetInEndSection": 978, "text": "The accelerator implements a version of the Needleman-Wunsch algorithm for nucleotide sequence alignment. Sequence lengths are constrained only by available memory; the product of sequence lengths in the current implementation can be up to 2(22). The machine is implemented as two NuBus boards connected to a Mac IIf/x, using a mixture of TTL and FPGA technology clocked at 10 MHz.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8481828", "endSection": "sections.0" } ] }, { "body": "List inhibtors targeting the mitochondrial permeability transition pore.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24968303", "http://www.ncbi.nlm.nih.gov/pubmed/20960209", "http://www.ncbi.nlm.nih.gov/pubmed/25063991", "http://www.ncbi.nlm.nih.gov/pubmed/12952973", "http://www.ncbi.nlm.nih.gov/pubmed/20966765", "http://www.ncbi.nlm.nih.gov/pubmed/20668412", "http://www.ncbi.nlm.nih.gov/pubmed/21542787", "http://www.ncbi.nlm.nih.gov/pubmed/25502879", "http://www.ncbi.nlm.nih.gov/pubmed/24615518", "http://www.ncbi.nlm.nih.gov/pubmed/21294074", "http://www.ncbi.nlm.nih.gov/pubmed/20937730", "http://www.ncbi.nlm.nih.gov/pubmed/24675465", "http://www.ncbi.nlm.nih.gov/pubmed/24627421", "http://www.ncbi.nlm.nih.gov/pubmed/15961375", "http://www.ncbi.nlm.nih.gov/pubmed/24998301", "http://www.ncbi.nlm.nih.gov/pubmed/22732280", "http://www.ncbi.nlm.nih.gov/pubmed/22198507", "http://www.ncbi.nlm.nih.gov/pubmed/24273204", "http://www.ncbi.nlm.nih.gov/pubmed/23536162", "http://www.ncbi.nlm.nih.gov/pubmed/25767484", "http://www.ncbi.nlm.nih.gov/pubmed/24349464", "http://www.ncbi.nlm.nih.gov/pubmed/24951958", "http://www.ncbi.nlm.nih.gov/pubmed/22745676", "http://www.ncbi.nlm.nih.gov/pubmed/25351957", "http://www.ncbi.nlm.nih.gov/pubmed/14627909", "http://www.ncbi.nlm.nih.gov/pubmed/21669242", "http://www.ncbi.nlm.nih.gov/pubmed/25793558", "http://www.ncbi.nlm.nih.gov/pubmed/24657357", "http://www.ncbi.nlm.nih.gov/pubmed/21297983", "http://www.ncbi.nlm.nih.gov/pubmed/25319443", "http://www.ncbi.nlm.nih.gov/pubmed/16516918", "http://www.ncbi.nlm.nih.gov/pubmed/21372381", "http://www.ncbi.nlm.nih.gov/pubmed/19819119", "http://www.ncbi.nlm.nih.gov/pubmed/24885907", "http://www.ncbi.nlm.nih.gov/pubmed/22197697", "http://www.ncbi.nlm.nih.gov/pubmed/24801220", "http://www.ncbi.nlm.nih.gov/pubmed/24297180", "http://www.ncbi.nlm.nih.gov/pubmed/24434143", "http://www.ncbi.nlm.nih.gov/pubmed/23423267", "http://www.ncbi.nlm.nih.gov/pubmed/18660440", "http://www.ncbi.nlm.nih.gov/pubmed/10413027" ], "ideal_answer": [ "Cyclosporine A\nAtractyloside\nN-metyl-4-isoleucine-cyclosporine\nSanglifehrin A \nTRO-19622", "The opening of the mitochondrial permeability transition pore appears to be inhibited by KB-R 7943, diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol, cyclosporin A (CsA) and BRL37344." ], "exact_answer": [ [ "Cyclosporine A" ], [ "Atractyloside" ], [ "N-metyl-4-isoleucine-cyclosporine", "NIM811" ], [ "Sanglifehrin A" ], [ "TRO-19622" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0005757", "http://amigo.geneontology.org/amigo/term/GO:0046902" ], "type": "list", "id": "5717cdd2070aa3d072000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Postconditioning with cyclosporine a reduces early renal dysfunction by inhibiting mitochondrial permeability transition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793558", "endSection": "title" }, { "offsetInBeginSection": 767, "offsetInEndSection": 837, "text": "mitochondrial permeability transition pore inhibitor (Cyclosporine A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24657357", "endSection": "abstract" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1283, "text": " treatment with the MPTP inhibitor atractyloside", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25351957", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1277, "text": " cyclosporine A, an MPTP inhibitor,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675465", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 382, "text": "NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24968303", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 580, "text": " The mPTP inhibitor sanglifehrin A (SfA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24615518", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1654, "text": "mPTP inhibitor, cyclosporin A (CsA),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25502879", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 708, "text": "cyclosporine A (CsA), a MPTP inhibitor, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24801220", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 736, "text": "The mPTP inhibitor NIM811,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24627421", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 767, "text": "A mPTP inhibitor (TRO-19622)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24273204", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1038, "text": "Cyclosporine A (CsA), a mitochondria permeability transition pore (MPTP) inhibitor, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24885907", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 668, "text": " and N-methyl-4-isoleucine cyclosporine (NIM811), an mPTP inhibitor, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23423267", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 539, "text": "mPTP inhibitor cyclosporin A (CsA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23536162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "ADP is not only a key substrate for ATP generation, but also a potent inhibitor of mitochondrial permeability transition pore (mPTP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24349464", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 734, "text": "MPTP inhibitor cyclosporin A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197697", "endSection": "abstract" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1506, "text": " mPTP inhibitor cyclosporin A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22198507", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1160, "text": "MPTP inhibitor cyclosporine A (CsA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20960209", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1158, "text": " the mPTP inhibitor cyclosporine A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20668412", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 780, "text": "The mPTP inhibitor cyclosporine A (CsA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19819119", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 671, "text": "Rather, we find that KB-R7943 inhibits opening of the mitochondrial permeability transition pore in permeabilized cells and isolated liver mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24434143", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1143, "text": "Our data reveal another mechanism through which KB-R7943 may protect against calcium-induced injury, as well as a novel means to inhibit the mitochondrial permeability transition pore.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24434143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "KB-R7943, a plasma membrane Na(+)/Ca(2+) exchanger inhibitor, blocks opening of the mitochondrial permeability transition pore.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24434143", "endSection": "title" }, { "offsetInBeginSection": 691, "offsetInEndSection": 890, "text": "Inhibitors of calcium/calmodulin-dependent protein kinase II, a mitochondrial Ca(2+) uniporter (MCU) regulator, also prevented MPTP formation and arachidonic acid release induced by A23187 and H2O2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297180", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1229, "text": "Unlike pyrrophenone, the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol and CsA blocked cell death and arachidonic acid release not by preventing mitochondrial calcium uptake but by inhibiting MPTP formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297180", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 1159, "text": "Incubation with \u03b23AR agonist (BRL37344, 7\u00a0\u03bcmol/L) significantly reduced cell death in isolated adult mouse cardiomyocytes during hypoxia/reoxygenation and decreased susceptibility to deleterious opening of the mitochondrial permeability transition pore (mPTP), via a mechanism dependent on the Akt-NO signaling pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24951958", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 1258, "text": "Here we show that antamanide inhibits the mitochondrial permeability transition pore, a central effector of cell death induction, by targeting the pore regulator cyclophilin D. Indeed, (i) permeability transition pore inhibition by antamanide is not additive with the cyclophilin D-binding drug cyclosporin A, (ii) the inhibitory action of antamanide on the pore requires phosphate, as previously shown for cyclosporin A; (iii) antamanide is ineffective in mitochondria or cells derived from cyclophilin D null animals, and (iv) abolishes CyP-D peptidyl-prolyl cis-trans isomerase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297983", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 816, "text": "Furthermore, in wild-type (non-transfected) SHSY5Y cells, the effects of lactacystin on mitochondrial function and cell viability are also prevented by cyclosporin A (1\u00a0\u03bcM) which blocks the activity of the mitochondrial permeability transition pore", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25319443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Exogenous zinc protects cardiac cells from reperfusion injury by targeting mitochondrial permeability transition pore through inactivation of glycogen synthase kinase-3beta.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18660440", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Bradykinin prevents reperfusion injury by targeting mitochondrial permeability transition pore through glycogen synthase kinase 3beta.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16516918", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permeability transition pore.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25063991", "endSection": "title" }, { "offsetInBeginSection": 698, "offsetInEndSection": 1111, "text": "Pre\u2014treatment of gallic acid and mitochondrially targeted gallic acid to sodium nitroprusside treated mitochondria not only significantly reduced the oxidative stress but also prevented mitochondrial permeability pore transition to a significant difference. Mitochondrially targeted gallic acid was found more effective in reducing oxidative stress and mitochondrial permeability pore transition than gallic acid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998301", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1245, "text": "Mitochondrially targeted gallic acid was found more effective in reducing oxidative stress and mitochondrial permeability pore transition than gallic acid. We conclude that mitochondrially targeted gallic acid can be used for preventing mitochondrial impairment caused by oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998301", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 917, "text": "The involvement of mitochondrial permeability transition pore was determined with a mitochondrial permeability transition pore opener atractyloside and a specific mitochondrial permeability transition pore inhibitor cyclosporin A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732280", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 256, "text": "Here we show that antamanide inhibits the mitochondrial permeability transition pore, a central effector of cell death induction, by targeting the pore regulator cyclophilin D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297983", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1111, "text": "Mitochondrially targeted gallic acid was found more effective in reducing oxidative stress and mitochondrial permeability pore transition than gallic acid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998301", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 955, "text": "Pre\u2014treatment of gallic acid and mitochondrially targeted gallic acid to sodium nitroprusside treated mitochondria not only significantly reduced the oxidative stress but also prevented mitochondrial permeability pore transition to a significant difference.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998301", "endSection": "abstract" } ] }, { "body": "What is ceritinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "http://www.ncbi.nlm.nih.gov/pubmed/24891360", "http://www.ncbi.nlm.nih.gov/pubmed/25228534", "http://www.ncbi.nlm.nih.gov/pubmed/25733882", "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "http://www.ncbi.nlm.nih.gov/pubmed/25101329", "http://www.ncbi.nlm.nih.gov/pubmed/25258279", "http://www.ncbi.nlm.nih.gov/pubmed/25170107", "http://www.ncbi.nlm.nih.gov/pubmed/24980964", "http://www.ncbi.nlm.nih.gov/pubmed/24670165", "http://www.ncbi.nlm.nih.gov/pubmed/25381900", "http://www.ncbi.nlm.nih.gov/pubmed/26018086", "http://www.ncbi.nlm.nih.gov/pubmed/25258420" ], "ideal_answer": [ "Ceritinib is a second generation tyrosine kinase inhibitor, that serves as an effective and approved oral therapy for patients with ALK-rearranged non-small cell lung cancer." ], "type": "summary", "id": "56d03a4d3975bb303a00000c", "snippets": [ { "offsetInBeginSection": 802, "offsetInEndSection": 930, "text": "We tested the antitumor activity of the next-generation ALK-TKI ceritinib in the patient with acquired resistance to alectinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228534", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 167, "text": "The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228534", "endSection": "abstract" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1446, "text": "Both ALK mutations conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs. Treatment of the patient with ceritinib led to a marked response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228534", "endSection": "abstract" }, { "offsetInBeginSection": 1735, "offsetInEndSection": 1891, "text": "The ability of ceritinib to overcome alectinib-resistance mutations suggests a potential role for sequential therapy with multiple next-generation ALK-TKIs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228534", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1251, "text": "Ceritinib is effective and approved for ALK-positive NSCLC in the acquired resistance setting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25381900", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 807, "text": "Ceritinib is an oral, potent, second-generation ALK inhibitor recently approved by the U.S. Food and Drug Administration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25101329", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 1003, "text": "Preclinical data showed impressive antitumor activity against crizotinib-resistant clones, and based on available data, ceritinib could represent a suitable option in crizotinib-resistant NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25101329", "endSection": "abstract" }, { "offsetInBeginSection": 1312, "offsetInEndSection": 1985, "text": "In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 1451, "text": "In particular, ceritinib effectively inhibits ALK harboring L1196M, G1269A, I1171T, and S1206Y mutations, and a cocrystal structure of ceritinib bound to ALK provides structural bases for this increased potency. However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.SIGNIFICANCE: The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "title" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1427, "text": "Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease. The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675041", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 1316, "text": "The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25458559", "endSection": "abstract" } ] }, { "body": "Which protein is found to be mutated in Friedreich's ataxia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12393810", "http://www.ncbi.nlm.nih.gov/pubmed/24242291", "http://www.ncbi.nlm.nih.gov/pubmed/20819074", "http://www.ncbi.nlm.nih.gov/pubmed/18206656", "http://www.ncbi.nlm.nih.gov/pubmed/12174969", "http://www.ncbi.nlm.nih.gov/pubmed/23247094", "http://www.ncbi.nlm.nih.gov/pubmed/11823441", "http://www.ncbi.nlm.nih.gov/pubmed/25430730", "http://www.ncbi.nlm.nih.gov/pubmed/16510442", "http://www.ncbi.nlm.nih.gov/pubmed/18463734", "http://www.ncbi.nlm.nih.gov/pubmed/12194387", "http://www.ncbi.nlm.nih.gov/pubmed/25929520", "http://www.ncbi.nlm.nih.gov/pubmed/18537827", "http://www.ncbi.nlm.nih.gov/pubmed/12140189", "http://www.ncbi.nlm.nih.gov/pubmed/25597503", "http://www.ncbi.nlm.nih.gov/pubmed/9700204", "http://www.ncbi.nlm.nih.gov/pubmed/16787388", "http://www.ncbi.nlm.nih.gov/pubmed/20674094" ], "ideal_answer": [ "It is generally accepted that Friedreich's ataxia (FRDA) is caused by a deficiency in frataxin expression, a mitochondrial protein involved in iron homeostasis, which mainly affects the brain, dorsal root ganglia of the spinal cord, heart and in certain cases the pancreas", "It is generally accepted that Friedreich's ataxia (FRDA) is caused by a deficiency in frataxin expression, a mitochondrial protein involved in iron homeostasis, which mainly affects the brain, dorsal root ganglia of the spinal cord, heart and in certain cases the pancreas." ], "exact_answer": [ "Frataxin" ], "type": "factoid", "id": "571f5c150fd6f91b68000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "It is generally accepted that Friedreich's ataxia (FRDA) is caused by a deficiency in frataxin expression, a mitochondrial protein involved in iron homeostasis, which mainly affects the brain, dorsal root ganglia of the spinal cord, heart and in certain cases the pancreas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25929520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Friedreich's ataxia is a severe neurodegenerative disease caused by the decreased expression of frataxin, a mitochondrial protein that stimulates iron-sulfur (Fe-S) cluster biogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25597503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "In eukaryotes, frataxin deficiency (FXN) causes severe phenotypes including loss of iron-sulfur (Fe-S) cluster protein activity, accumulation of mitochondrial iron and leads to the neurodegenerative disease Friedreich's ataxia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430730", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 806, "text": "Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C. elegans, while its partial deficiency extends animal lifespan in a p53 dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23247094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Friedreich ataxia (FRDA) is a neurodegenerative disease characterized by a decreased expression of the mitochondrial protein frataxin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24242291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Friedreich's ataxia results from a deficiency in the mitochondrial protein frataxin, which carries single point mutations in some patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18537827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Friedreich's ataxia (FRDA), an autosomal recessive cardio- and neurodegenerative disease, is caused by low expression of frataxin, a small mitochondrial protein, encoded in the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12140189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The severe reduction in mRNA and protein levels of the mitochondrial protein frataxin, encoded by the X25 gene, causes Friedreich ataxia (FRDA), the most common form of recessive hereditary ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12393810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11823441", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Friedreich ataxia is a human neurodegenerative and myocardial disease caused by decreased expression of the mitochondrial protein frataxin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16510442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Friedreich ataxia, an autosomal recessive neurodegenerative and cardiac disease, is caused by abnormally low levels of frataxin, an essential mitochondrial protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease caused by a deficiency of frataxin, a conserved mitochondrial protein of unknown function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11823441", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1234, "text": "This review will focus on the progress of potential treatment strategies for Friedreich ataxia that target the GAA expanded gene and seek to increase the level of frataxin message and protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18206656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Frataxin is a mitochondrial protein deficient in Friedreich ataxia (FRDA) and which is associated with abnormal intramitochondrial iron handling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9700204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "The neurodegenerative disorder FRDA (Friedreich's ataxia) results from a deficiency in frataxin, a putative iron chaperone, and is due to the presence of a high number of GAA repeats in the coding regions of both alleles of the frataxin gene, which impair protein expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16787388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The Friedreich's ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20819074", "endSection": "title" }, { "offsetInBeginSection": 74, "offsetInEndSection": 348, "text": "It is caused by deficiency of frataxin, a highly conserved nuclear-encoded protein localized in mitochondria. The DNA abnormality found in 98% of Friedreich's ataxia chromosomes is the unstable hyperexpansion of a GAA triplet repeat in the first intron of the frataxin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12194387", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 348, "text": "The DNA abnormality found in 98% of Friedreich's ataxia chromosomes is the unstable hyperexpansion of a GAA triplet repeat in the first intron of the frataxin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12194387", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 771, "text": "Interestingly, Drosophila frataxin (dfh), which causes Friedreich's ataxia if mutated in humans, displayed an interacting effect with Al, suggesting Friedreich's ataxia patients might be more susceptible to Al toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20674094", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 625, "text": "Although the Friedreich's ataxia phenotype results from decreased expression of a mitochondrially targeted protein, frataxin, mitochondrial myopathy has not been described as a feature of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12174969", "endSection": "abstract" } ] }, { "body": "Which is the process that Conserved noncoding elements mostly regulate?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19492354", "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "http://www.ncbi.nlm.nih.gov/pubmed/21629789", "http://www.ncbi.nlm.nih.gov/pubmed/21731768", "http://www.ncbi.nlm.nih.gov/pubmed/17096848", "http://www.ncbi.nlm.nih.gov/pubmed/21478460", "http://www.ncbi.nlm.nih.gov/pubmed/21175683", "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "http://www.ncbi.nlm.nih.gov/pubmed/16630819", "http://www.ncbi.nlm.nih.gov/pubmed/18056681", "http://www.ncbi.nlm.nih.gov/pubmed/17442748", "http://www.ncbi.nlm.nih.gov/pubmed/23042552", "http://www.ncbi.nlm.nih.gov/pubmed/19698106", "http://www.ncbi.nlm.nih.gov/pubmed/19704032", "http://www.ncbi.nlm.nih.gov/pubmed/18334644", "http://www.ncbi.nlm.nih.gov/pubmed/19073165" ], "ideal_answer": [ "Conserved noncoding elements play a fundamental role in regulating animal development" ], "exact_answer": [ "Development" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017124" ], "type": "factoid", "id": "51387022bee46bd34c000002", "snippets": [ { "offsetInBeginSection": 507, "offsetInEndSection": 681, "text": "Much evidence suggests that CNEs are selectively constrained and not mutational cold-spots, and there is evidence that some CNEs play a role in the regulation of development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21478460", "endSection": "sections.0" }, { "offsetInBeginSection": 1463, "offsetInEndSection": 1676, "text": "This result suggests that there is widespread adaptation in mammalian conserved noncoding DNA elements, some of which have been implicated in the regulation of crucially important processes, including development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21478460", "endSection": "sections.0" }, { "offsetInBeginSection": 143, "offsetInEndSection": 345, "text": "Some characteristics of CNEs include their high frequency in mammalian genomes, their potential regulatory role in gene expression, and their enrichment in gene deserts nearby master developmental genes", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175683", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Animal genomes possess highly conserved cis-regulatory sequences that are often found near genes that regulate transcription and development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704032", "endSection": "sections.0" }, { "offsetInBeginSection": 585, "offsetInEndSection": 677, "text": "HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "sections.0" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1391, "text": "HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073165", "endSection": "sections.0" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1596, "text": "These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18334644", "endSection": "sections.0" }, { "offsetInBeginSection": 480, "offsetInEndSection": 648, "text": "Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "endSection": "sections.0" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1412, "text": "The majority of tetrapod-specific UCEs are noncoding and associated with genes involved in regulation of transcription and development.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056681", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "endSection": "sections.0" }, { "offsetInBeginSection": 792, "offsetInEndSection": 955, "text": "In 74% of cases, we were able to assign a specific set of paralogous genes with annotation relating to transcriptional regulation and/or development to each family", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16630819", "endSection": "sections.0" } ] }, { "body": "What is the main mechanism by which human papillomavirus proteins E6 and E7 contribute to cell transformation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10809724", "http://www.ncbi.nlm.nih.gov/pubmed/17768080", "http://www.ncbi.nlm.nih.gov/pubmed/9537653", "http://www.ncbi.nlm.nih.gov/pubmed/8207801", "http://www.ncbi.nlm.nih.gov/pubmed/1331501", "http://www.ncbi.nlm.nih.gov/pubmed/9223480", "http://www.ncbi.nlm.nih.gov/pubmed/20088881", "http://www.ncbi.nlm.nih.gov/pubmed/16249186", "http://www.ncbi.nlm.nih.gov/pubmed/8397367", "http://www.ncbi.nlm.nih.gov/pubmed/21643539", "http://www.ncbi.nlm.nih.gov/pubmed/10698500", "http://www.ncbi.nlm.nih.gov/pubmed/17332339", "http://www.ncbi.nlm.nih.gov/pubmed/9817205", "http://www.ncbi.nlm.nih.gov/pubmed/21980285" ], "ideal_answer": [ "Although they may have other targets, human papillomavirus proteins E6 and E7 interact with and block the function of p53 and pRb, respectively, therefore deregulating cell cycle and leading to cellular transformation." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050725", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0019087" ], "type": "summary", "id": "5178444e8ed59a060a000037", "snippets": [ { "offsetInBeginSection": 816, "offsetInEndSection": 1116, "text": "The ability of high-risk HPV E6 and E7 protein to promote the degradation of p53 and pRb, respectively, has been suggested as a mechanism by which HPV oncogenes induce cellular transformation. E6 and E7 abrogate cell cycle checkpoints and induce genomic instability that leads to malignant conversion", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21643539", "endSection": "sections.0" }, { "offsetInBeginSection": 686, "offsetInEndSection": 891, "text": "The results showed that tumorigenicity and decreased serum requirement were associated with the ability of E6 to bind to p53, although the subsequent degradation of p53 was not required for these functions", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9537653", "endSection": "sections.0" }, { "offsetInBeginSection": 583, "offsetInEndSection": 828, "text": "The E7 mutants chosen had either an in-frame deletion in the conserved region 2 (CR2) domain, which is required for binding of the retinoblastoma tumor suppressor protein (pRb) and pRb-like proteins, or an in-frame deletion in the E7 CR1 domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9223480", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "The recognition of a causal relationship between human papillomaviruses and cancer almost 30 years ago led to a rapid expansion of knowledge in the field, resulting in the description of the main mediators of HPV-induced carcinogenesis, the viral proteins E6 and E7. These oncoproteins show a remarkable pleiotropism in binding host-cell proteins, with the tumour suppressor genes p53 and pRb as their major targets.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17768080", "endSection": "sections.0" }, { "offsetInBeginSection": 567, "offsetInEndSection": 793, "text": "First, we found that human papillomavirus E6 and E7 oncogenes, which block the function of the p53 and Rb tumor suppressors, respectively, and SV40 small t antigen were required to allow mutant K-Ras(12D) growth transformation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17332339", "endSection": "sections.0" }, { "offsetInBeginSection": 427, "offsetInEndSection": 618, "text": "In recent years, it has become clear that in addition to E6-induced degradation of p53 tumor suppressor protein, other targets of E6 are required for mammary epithelial cells immortalization.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10809724", "endSection": "sections.0" }, { "offsetInBeginSection": 364, "offsetInEndSection": 498, "text": "a general requirement for oncoproteins such as human papillomavirus E6 and E7 has suggested that the p53 and Rb pathways are targeted.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9817205", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Transformation by the human papillomavirus (HPV) early gene products, E6 and E7, involves their interaction with cellular proteins p53 and Rb.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8207801", "endSection": "sections.0" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1939, "text": "The results from this study support the theory that p53 protein binds HPV-16/18 E6 protein in the cell cytoplasm, thus preventing p53 from exerting its tumor-suppressor function in the nucleus. Hence, inactivation of wild-type p53 by p53-E6 complex formation in cervical cancer may be a critical step in malignant transformation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8397367", "endSection": "sections.0" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1331, "text": "the E7-RbAB interaction involves multiple motifs within the N-terminal domain of E7 and at least two conserved interaction surfaces in RbAB.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20088881", "endSection": "sections.0" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1053, "text": "Based on these studies we present a mechanistic model for how E7 displaces E2F from pRb", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16249186", "endSection": "sections.0" }, { "offsetInBeginSection": 614, "offsetInEndSection": 761, "text": "The E7 protein of human papillomavirus type 16 contains an element that binds to pRB and appears to be functionally homologous to the E1A sequences", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1331501", "endSection": "sections.0" }, { "offsetInBeginSection": 185, "offsetInEndSection": 327, "text": "Several of the biological activities of HPV16 E7 are mediated by inactivation of the members of the pocket protein family, pRb, p107 and p130.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10698500", "endSection": "sections.0" } ] }, { "body": "List bacterial species identified in the iceman tissues.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10640948", "http://www.ncbi.nlm.nih.gov/pubmed/10861348", "http://www.ncbi.nlm.nih.gov/pubmed/24941044" ], "ideal_answer": [ "Spirochete Treponema denticola\nClostridium perfringens\nClostridium ghonii\nClostridium sordellii\nEubacterium tenue\nBacteroides sp\nVibrio\nSphingomonas\nAfipia\nCurtobacterium\nMicrobacterium\nAgromyces" ], "exact_answer": [ [ "Spirochete Treponema denticola" ], [ "Clostridium perfringens" ], [ "Clostridium ghonii" ], [ "Clostridium sordellii" ], [ "Eubacterium tenue" ], [ "Bacteroides sp" ], [ "Vibrio" ], [ "Sphingomonas" ], [ "Afipia" ], [ "Curtobacterium" ], [ "Microbacterium" ], [ "Agromyces" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004755", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001419", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016045" ], "type": "list", "id": "56d1fd67f22319765a000002", "snippets": [ { "offsetInBeginSection": 177, "offsetInEndSection": 355, "text": "Here, we report the molecular detection of the oral spirochete Treponema denticola in ancient human tissue biopsies of the Iceman, a 5,300-year-old Copper Age natural ice mummy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24941044", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1500, "text": "The colon, on the other hand, contains several members of the fecal flora of humans, such as Clostridium perfringens, C. ghonii, C. sordellii, Eubacterium tenue, and Bacteroides sp. The Iceman's colon, however, was found to contain, rather unexpectedly, also some members of the genus Vibrio. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10861348", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 822, "text": " while the untreated skin still bears the remains of large numbers of bacteria belonging to the genera Sphingomonas, Afipia, Curtobacterium, Microbacterium, Agromyces, and others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10640948", "endSection": "abstract" } ] }, { "body": "Which properties of the mRNA does N6-methyladenosine (m6A) affect?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26121403", "http://www.ncbi.nlm.nih.gov/pubmed/25412662", "http://www.ncbi.nlm.nih.gov/pubmed/19180239", "http://www.ncbi.nlm.nih.gov/pubmed/25475057", "http://www.ncbi.nlm.nih.gov/pubmed/3029112", "http://www.ncbi.nlm.nih.gov/pubmed/9409616", "http://www.ncbi.nlm.nih.gov/pubmed/6592581", "http://www.ncbi.nlm.nih.gov/pubmed/6318439", "http://www.ncbi.nlm.nih.gov/pubmed/22575960", "http://www.ncbi.nlm.nih.gov/pubmed/25452335", "http://www.ncbi.nlm.nih.gov/pubmed/25569111", "http://www.ncbi.nlm.nih.gov/pubmed/24981863", "http://www.ncbi.nlm.nih.gov/pubmed/25430002" ], "ideal_answer": [ "N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate. m6A predominantly and directly reduces mRNA stability." ], "exact_answer": [ "mRNA stability" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012333", "http://www.biosemantics.org/jochem#4252558" ], "type": "factoid", "id": "56df03c751531f7e3300000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26121403", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 722, "text": "m(6)A predominantly and directly reduces mRNA stability, including that of key na\u00efve pluripotency-promoting transcripts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25569111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Recent discoveries of reversible N(6)-methyladenosine (m(6)A) methylation on messenger RNA (mRNA) and mapping of m(6)A methylomes in mammals and yeast have revealed potential regulatory functions of this RNA modification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430002", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 764, "text": "Monitoring m6A levels upon WTAP depletion allowed the definition of accurate and near single-nucleotide resolution methylation maps and their classification into WTAP-dependent and -independent sites. WTAP-dependent sites are located at internal positions in transcripts, topologically static across a variety of systems we surveyed, and inversely correlated with mRNA stability, consistent with a role in establishing \"basal\" degradation rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24981863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Methylations of adenosine residues (m6A) in pre-mRNA are important for formation of late simian virus 40 mRNAs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6318439", "endSection": "title" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1493, "text": "The data argues for a role of internal m6A moieties in modulating the processing-linked transport of mRNA from the nucleus to the cytoplasm of nontransformed cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6318439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "N6-Methyladenosine (m6A) residues, which are found internally in viral and cellular mRNA populations at the sequences Apm6ApC and Gpm6ApC, have been proposed to play a role in mRNA processing and transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6592581", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The role of Fat Mass and Obesity-associated protein (FTO) and its substrate N6-methyladenosine (m6A) in mRNA processing and adipogenesis remains largely unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25412662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "N6-methyladenosine (m6A) is a common modification of mRNA with potential roles in fine-tuning the RNA life cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24981863", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 248, "text": "The results of that study and of experiments using inhibitors of methylation suggest that m6A might be involved in mRNA processing events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3029112", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 300, "text": "Previous studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9409616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": " The methylation of internal adenosine residues in eukaryotic mRNA, forming N6-methyladenosine (m6A), is catalyzed by a complex multicomponent enzyme. Previous studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9409616", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 615, "text": "Previous studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known. As a step toward better understanding the mechanism and function of this ubiquitous posttranscriptional modification, we have shown that HeLa mRNA (N6-adenosine)-methyltransferase requires at least two separate protein factors, MT-A and MT-B, and MT-A contains the AdoMet binding site on a 70-kDa subunit (MT-A70).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9409616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "The methylation of internal adenosine residues in eukaryotic mRNA, forming N6-methyladenosine (m6A), is catalyzed by a complex multicomponent enzyme. Previous studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9409616", "endSection": "abstract" } ] }, { "body": "What is the implication of histone lysine methylation in medulloblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23179372", "http://www.ncbi.nlm.nih.gov/pubmed/23184418", "http://www.ncbi.nlm.nih.gov/pubmed/19270706" ], "ideal_answer": [ "Aberrant patterns of H3K4, H3K9, and H3K27 histone lysine methylation were shown to result in histone code alterations, which induce changes in gene expression, and affect the proliferation rate of cells in medulloblastoma." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034968", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031060", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051567", "http://www.disease-ontology.org/api/metadata/DOID:3873", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016571", "http://www.disease-ontology.org/api/metadata/DOID:3858" ], "type": "summary", "id": "5539062dbc4f83e828000013", "snippets": [ { "offsetInBeginSection": 280, "offsetInEndSection": 1148, "text": "Through targeted re-sequencing, we identified mutations of MLL2 in 8 % (14/175) of MBs, the majority of which were loss of function. Notably, we also report mutations affecting the MLL2-binding partner KDM6A, in 4 % (7/175) of tumors. While MLL2 mutations were independent of age, gender, histological subtype, M-stage or molecular subgroup, KDM6A mutations were most commonly identified in Group 4 MBs, and were mutually exclusive with MLL2 mutations. Immunohistochemical staining for H3K4me3 and H3K27me3, the chromatin effectors of MLL2 and KDM6A activity, respectively, demonstrated alterations of the histone code in 24 % (53/220) of MBs across all subgroups. Correlating these MLL2- and KDM6A-driven histone marks with prognosis, we identified populations of MB with improved (K4+/K27-) and dismal (K4-/K27-) outcomes, observed primarily within Group 3 and 4 MBs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184418", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 923, "text": "we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270706", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1181, "text": "Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Aberrant patterns of H3K4 and H3K27 histone lysine methylation occur across subgroups in medulloblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184418", "endSection": "title" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1186, "text": "Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Recent studies showed frequent mutations in histone H3 lysine 27 (H3K27) demethylases in medulloblastomas of Group 3 and Group 4, suggesting a role for H3K27 methylation in these tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23179372", "endSection": "abstract" } ] }, { "body": "What is the Orco protein in mosquitos?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22269900", "http://www.ncbi.nlm.nih.gov/pubmed/23292750", "http://www.ncbi.nlm.nih.gov/pubmed/23894621", "http://www.ncbi.nlm.nih.gov/pubmed/22272331", "http://www.ncbi.nlm.nih.gov/pubmed/21555561", "http://www.ncbi.nlm.nih.gov/pubmed/23352695", "http://www.ncbi.nlm.nih.gov/pubmed/22174894", "http://www.ncbi.nlm.nih.gov/pubmed/23719379" ], "ideal_answer": [ "Odorant co-receptor." ], "concepts": [ "http://www.uniprot.org/uniprot/OR83B_DROME", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009033" ], "type": "summary", "id": "54f616cd5f206a0c0600000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Insect odorant receptors function as heteromeric odorant-gated cation channels comprising a conventional odorant-sensitive tuning receptor, and a conserved co-receptor (Orco)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894621", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 753, "text": "Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels comprising a variable ligand-selective subunit and an obligate co-receptor called Orco", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23719379", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 804, "text": "Surprisingly, mutation of the obligate olfactory coreceptor (Orco) does not abolish CO(2) aversion during walking yet eliminates CO(2) tracking in flight. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23352695", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 547, "text": " Most odors are detected via a family of odorant receptors (ORs), which form heteromeric complexes consisting of a well-conserved OR co-receptor (Orco) ion channel and a non-conserved tuning OR that provides coding specificity to each complex. Orco functions as a non-selective cation channel and is expressed in the majority of olfactory receptor neurons (ORNs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272331", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 321, "text": "a novel OR co-receptor (Orco)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "In insects, odor cues are discriminated through a divergent family of odorant receptors (ORs). A functional OR complex consists of both a conventional odorant-binding OR and a nonconventional coreceptor (Orco) that is highly conserved across insect taxa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21555561", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 156, "text": "Insect odorant receptors (ORs) function as odorant-gated ion channels consisting of a conventional, odorant-binding OR and the Orco coreceptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22174894", "endSection": "abstract" } ] }, { "body": "List some ways to reverse Tau hyperphosphorylation in Tauopathies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12212772", "http://www.ncbi.nlm.nih.gov/pubmed/16806196", "http://www.ncbi.nlm.nih.gov/pubmed/20471717", "http://www.ncbi.nlm.nih.gov/pubmed/16687499", "http://www.ncbi.nlm.nih.gov/pubmed/18755209" ], "ideal_answer": [ "Different ways have been used to try to reverse Tau hyperphosphorylation through administration of inhibitors such as: 7-nitroindazole, memantine, glycogen synthase kinase-3 inhibitors. \nOther approaches are transplantation of Human umbilical cord blood-derived mesenchymal stem cells and administration of M1 muscarinic agonists." ], "exact_answer": [ [ "Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) transplantation" ], [ "Administration of 7-nitroindazole (neuronal nitric oxide synthase inhibitor)" ], [ "Administration of Memantine (un-competitive inhibitor of N-methyl-D-aspartate receptors)" ], [ "Administration glycogen synthase kinase-3 (GSK-3) inhibitors" ], [ "Administration of M1 muscarinic agonists such as AF150(S) and AF267B" ] ], "concepts": [ "http://www.uniprot.org/uniprot/TAU_MOUSE", "http://www.uniprot.org/uniprot/TAU_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010766", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042327", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016310", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016875" ], "type": "list", "id": "517775c78ed59a060a000033", "snippets": [ { "offsetInBeginSection": 529, "offsetInEndSection": 617, "text": "tau hyperphosphorylation were dramatically reduced in hUCB-MSC transplanted APP/PS1 mice", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20471717", "endSection": "sections.0" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1384, "text": "Administration of 7-nitroindazole to CMS-exposed old rats significantly (p=0.002) increased GAD activity, decreased glutamate levels (7.19+/-3.19 vs. 763.9+/-91 micromol/g tissue protein; p=0.0005), and decreased phosphorylation of tau proteins compared to CMS exposed rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18755209", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Changes in glutamate decarboxylase enzyme activity and tau-protein phosphorylation in the hippocampus of old rats exposed to chronic mild stress: reversal with the neuronal nitric oxide synthase inhibitor 7-nitroindazole.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18755209", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its reversal by Memantine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16806196", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Full reversal of Alzheimer's disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16687499", "endSection": "title" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1854, "text": "Here, we show that transgene shutdown in symptomatic mice leads to normal GSK-3 activity, normal phospho-tau levels, diminished neuronal death, and suppression of the cognitive deficit, thus further supporting the potential of GSK-3 inhibitors for AD therapeutics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16687499", "endSection": "sections.0" }, { "offsetInBeginSection": 524, "offsetInEndSection": 795, "text": "These effects can be combined with the beneficial effects of these compounds on some other major hallmarks of Alzheimer's disease (AD) (e.g. tau hyperphosphorylation and paired helical filaments [PHF]; and loss of cholinergic function conducive to cognitive impairments.)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12212772", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 522, "text": "The M1 muscarinic agonists AF102B (Cevimeline, EVOXACTM: prescribed in USA and Japan for Sjogren's Syndrome), AF150(S) and AF267B--1) are neurotrophic and synergistic with neurotrophins such as nerve growth factor and epidermal growth factor; 2) elevate the non-amyloidogenic amyloid precursor protein (alpha-APPs) in vitro and decrease beta-amyloid (A beta) levels in vitro and in vivo; and 3) inhibit A beta- and oxidative-stress-induced cell death and apoptosis in PC12 cells transfected with the M1 muscarinic receptor", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12212772", "endSection": "sections.0" } ] }, { "body": "What is the role of 5hmC (5 hydroxy-methyl-Cytocine) in differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24838624", "http://www.ncbi.nlm.nih.gov/pubmed/21514197", "http://www.ncbi.nlm.nih.gov/pubmed/22722204", "http://www.ncbi.nlm.nih.gov/pubmed/23403924", "http://www.ncbi.nlm.nih.gov/pubmed/21873190", "http://www.ncbi.nlm.nih.gov/pubmed/25263596", "http://www.ncbi.nlm.nih.gov/pubmed/22234893", "http://www.ncbi.nlm.nih.gov/pubmed/22730288", "http://www.ncbi.nlm.nih.gov/pubmed/24735881", "http://www.ncbi.nlm.nih.gov/pubmed/25179373", "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "http://www.ncbi.nlm.nih.gov/pubmed/26275994", "http://www.ncbi.nlm.nih.gov/pubmed/21460836" ], "ideal_answer": [ "The balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development. By mapping DNA methylation and hydroxymethylation at base resolution, we find that deletion of Tet2 causes extensive loss of 5hmC at enhancers, accompanied by enhancer hypermethylation, reduction of enhancer activity, and delayed gene induction in the early steps of differentiation.", "Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers " ], "type": "summary", "id": "56c5ade15795f9a73e000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "5-Methylcytosine (5 mC) in genomic DNA has important epigenetic functions in embryonic development and tumor biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22234893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722204", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 434, "text": "Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722204", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1054, "text": "This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21514197", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 766, "text": "Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg-cell-specific hypomethylation pattern and stable Foxp3 expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275994", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 908, "text": "Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "5-Hydroxymethylcytosine (5hmC), converted from 5-methylcytocine (5mC) by Tet family of dioxygenases (Tet1, Tet2, and Tet3), is enriched in the embryonic stem cells (ESCs) and in the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24838624", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 586, "text": "We found that Tet3 expression is basically undetectable in ESCs, but its level increases rapidly during neuronal differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24838624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263596", "endSection": "title" }, { "offsetInBeginSection": 293, "offsetInEndSection": 496, "text": "Recent experiments have demonstrated that enhancers are enriched for 5-hydroxymethylcytosine (5hmC), an oxidization product of the Tet family of 5mC dioxygenases and an intermediate of DNA demethylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263596", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 892, "text": "By mapping DNA methylation and hydroxymethylation at base resolution, we find that deletion of Tet2 causes extensive loss of 5hmC at enhancers, accompanied by enhancer hypermethylation, reduction of enhancer activity, and delayed gene induction in the early steps of differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Loss of Tet enzymes compromises proper differentiation of embryonic stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24735881", "endSection": "title" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1132, "text": "These findings suggest a requirement for Tet- and 5hmC-mediated DNA demethylation in proper regulation of gene expression during ESC differentiation and development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24735881", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 486, "text": "We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22730288", "endSection": "title" }, { "offsetInBeginSection": 168, "offsetInEndSection": 506, "text": "In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells and during adipocyte differentiation of mouse 3T3-L1 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22730288", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1562, "text": "Hence, acquisition of 5hmC in cell-specific distal regulatory regions may represent a major event of enhancer progression toward an active state and participate in selective activation of tissue-specific genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22730288", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 828, "text": "We find that 5hmC is mostly associated with euchromatin and that whereas 5mC is under-represented at gene promoters and CpG islands, 5hmC is enriched and is associated with increased transcriptional levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21460836", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1300, "text": "Knockdown of Tet1 and Tet2 causes downregulation of a group of genes that includes pluripotency-related genes (including Esrrb, Prdm14, Dppa3, Klf2, Tcl1 and Zfp42) and a concomitant increase in methylation of their promoters, together with an increased propensity of ES cells for extraembryonic lineage differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21460836", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 991, "text": " Tet2 deficiency led to decreased genomic levels of 5hmC and augmented the size of the hematopoietic stem/progenitor cell pool in a cell-autonomous manner. In competitive transplantation assays, Tet2-deficient HSCs were capable of multilineage reconstitution and possessed a competitive advantage over wild-type HSCs, resulting in enhanced hematopoiesis into both lymphoid and myeloid lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21873190", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 319, "text": "However, the role of 5hmC and Tet family in the process of ESC differentiation especially neuronal differentiation remains elusive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24838624", "endSection": "abstract" }, { "offsetInBeginSection": 786, "offsetInEndSection": 926, "text": "Our data constitute a valuable resource that will facilitate detailed analysis of the role of 5hmC in T-cell development and differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 367, "text": "More recently, a possible role of 5hmC as an epigenetic modifier and/or transcriptional regulator has started to emerge, with altered levels in early embryonic development, embryonic stem (ES) cell differentiation and tumours (Tahiliani et al, 2009; Yang et al, 2012). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23403924", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 896, "text": "Here we report a method that combines TET-assisted bisulfite conversion with Illumina 450K DNA methylation arrays for a low-cost high-throughput approach that distinguishes 5hmC and 5mC signals at base resolution. Implementing this approach, termed \"TAB-array\", we assessed DNA methylation dynamics in the differentiation of human pluripotent stem cells into cardiovascular progenitors and neural precursor cells. With the ability to discriminate 5mC and 5hmC, we identified a large number of novel dynamically methylated genomic regions that are implicated in the development of these lineages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25179373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "5-hydroxy methyl cytosine (5hmC) is a modification identified in vertebrates several decades ago. More recently, a possible role of 5hmC as an epigenetic modifier and/or transcriptional regulator has started to emerge, with altered levels in early embryonic development, embryonic stem (ES) cell differentiation and tumours (Tahiliani et al, 2009; Yang et al, 2012).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23403924", "endSection": "abstract" } ] }, { "body": "Which is the histone residue methylated by MLL1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18562676", "http://www.ncbi.nlm.nih.gov/pubmed/16651450", "http://www.ncbi.nlm.nih.gov/pubmed/19855399", "http://www.ncbi.nlm.nih.gov/pubmed/17942719", "http://www.ncbi.nlm.nih.gov/pubmed/15960975", "http://www.ncbi.nlm.nih.gov/pubmed/21875999", "http://www.ncbi.nlm.nih.gov/pubmed/22666422", "http://www.ncbi.nlm.nih.gov/pubmed/21124902", "http://www.ncbi.nlm.nih.gov/pubmed/19187761", "http://www.ncbi.nlm.nih.gov/pubmed/18838538", "http://www.ncbi.nlm.nih.gov/pubmed/15941828", "http://www.ncbi.nlm.nih.gov/pubmed/17168535", "http://www.ncbi.nlm.nih.gov/pubmed/21113167", "http://www.ncbi.nlm.nih.gov/pubmed/22488473", "http://www.ncbi.nlm.nih.gov/pubmed/19818711", "http://www.ncbi.nlm.nih.gov/pubmed/19219072", "http://www.ncbi.nlm.nih.gov/pubmed/23399917", "http://www.ncbi.nlm.nih.gov/pubmed/20861184", "http://www.ncbi.nlm.nih.gov/pubmed/22046413", "http://www.ncbi.nlm.nih.gov/pubmed/19481096", "http://www.ncbi.nlm.nih.gov/pubmed/23038103" ], "ideal_answer": [ "Histone H3 at lysine 4 (H3K4)" ], "exact_answer": [ "H3K4" ], "concepts": [ "http://www.uniprot.org/uniprot/MLL1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042054", "http://www.uniprot.org/uniprot/SETMR_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042800", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011495", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0018024", "http://www.uniprot.org/uniprot/MLL1_HUMAN" ], "type": "factoid", "id": "533be71dfd9a95ea0d000009", "snippets": [ { "offsetInBeginSection": 771, "offsetInEndSection": 894, "text": "lack of interaction with the histone methyltransferase, MLL1, resulting in decreased histone H3K4me3 and gene transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23399917", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1446, "text": "histone H3K4me3 methylase MLL1 complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23038103", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 304, "text": "MEN1 encodes menin, a subunit of MLL1/MLL2-containing histone methyltransferase complexes that trimethylate histone H3 at lysine 4 (H3K4me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22666422", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 837, "text": "MLL1, MLL5, Set1 and ASH1 to be highly up-regulated during transdifferentiation of HSCs. All of these histone methyltransferases regulate methylation of lysine 4 of histone H3, which is a signature of actively transcribed genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488473", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 897, "text": "MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22046413", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 227, "text": "H3K4) in Saccharomyces cerevisiae is implemented by Set1/COMPASS, which was originally purified based on the similarity of yeast Set1 to human MLL1 and Drosophila melanogaster Trithorax (Trx)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875999", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 170, "text": "istone H3 lysine 4 (K4) methylation is a prevalent mark associated with transcription activation and is mainly catalyzed by the MLL/SET1 family histone methyltransferase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21124902", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1007, "text": "Mutations in the MLL1 SET domain that fail to support overall H3 K4 methylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21124902", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 562, "text": "MLL1, a mammalian homolog of Drosophila trithorax, is an H3K4-specific methyltransferase implicated in transcriptional control", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21113167", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 827, "text": "We show that the mixed lineage leukemia 1 (MLL1) protein, a histone methyltransferase specific for H3K4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20861184", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1046, "text": "MLL1 histone H3 Lys4 methyltransferase complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19855399", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 264, "text": "MLL1 histone methyltransferase (H3K4me3) complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19818711", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 468, "text": "In the human MLL1 (mixed-lineage leukemia-1) HMT complex, DPY-30L binds to the BRE2 homolog ASH2L in order to regulate histone 3-lysine 4 trimethylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19481096", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1097, "text": "MLL1 and MLL2 H3K4 methyltransferase complexes are tethered by p52 on the MMP9 but not on the IkappaBalpha promoter, and the H3K4 trimethyltransferase activity r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19219072", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 261, "text": "The biological function of MLL1 is mediated by the histone H3K4 methyltransferase activity of the carboxyl-terminal SET domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19187761", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 313, "text": "Set1/COMPASS is capable of methylating H3K4, a posttranslational modification associated with actively transcribed genes. There is only one Set1 in yeast; yet in mammalian cells there are multiple H3K4 methylases, including Set1A/B, forming human COMPASS complexes, and MLL1-4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18838538", "endSection": "abstract" }, { "offsetInBeginSection": 1478, "offsetInEndSection": 1541, "text": " trimethylated H3K4 histones and histone methyltransferase MLL1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18562676", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 815, "text": " lacZ knock-in allele of mixed-lineage leukemia 1 (Mll1), a histone methyltransferase expressed in GABAergic and other cortical neurons, resulted in decreased H3K4 methylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17942719", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 169, "text": "effectors of H3K4 methylation is mixed-lineage leukemia 1 (MLL1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17168535", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 204, "text": "MLL1/MLL2 histone methyltransferase complexes specific for Lys4 of histone H3 (H3K4)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16651450", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 80, "text": "H3 K4 methyltransferase MLL1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960975", "endSection": "title" }, { "offsetInBeginSection": 374, "offsetInEndSection": 508, "text": "purified complex has a robust MLL1-mediated histone methyltransferase activity that can effect mono-, di-, and trimethylation of H3 K4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960975", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 501, "text": "MLL1 localizes with RNA polymerase II (Pol II) to the 5' end of actively transcribed genes, where histone H3 lysine 4 trimethylation occurs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15941828", "endSection": "abstract" } ] }, { "body": "What is CRISPRi?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26098216", "http://www.ncbi.nlm.nih.gov/pubmed/25409531", "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "http://www.ncbi.nlm.nih.gov/pubmed/25566532", "http://www.ncbi.nlm.nih.gov/pubmed/23452860", "http://www.ncbi.nlm.nih.gov/pubmed/23849981", "http://www.ncbi.nlm.nih.gov/pubmed/26047700", "http://www.ncbi.nlm.nih.gov/pubmed/26080438" ], "ideal_answer": [ "Clustered regularly interspaced palindromic repeats interference (CRISPRi). This discovery tool is is used for genetic screening based on loss-of-function phenotypes.", "The Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) system is used for targeted silencing of transcription in different types of cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR pathway, requiring only the coexpression of a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA). The Cas9-sgRNA complex binds to DNA elements complementary to the sgRNA and causes a steric block that halts transcript elongation by RNA polymerase, resulting in the repression of the target gene. CRISPRi provides a simplified approach for rapid gene repression within 1-2 weeks. The method can also be adapted for high-throughput interrogation of genome-wide gene functions and genetic interactions, thus providing a complementary approach to RNA interference, which can be used in a wider variety of organisms." ], "type": "summary", "id": "56f157a52ac5ed1459000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "CRISPR interference (CRISPRi) for sequence-specific control of gene expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "endSection": "title" }, { "offsetInBeginSection": 242, "offsetInEndSection": 770, "text": "(CRISPRi), for targeted silencing of transcription in bacteria and human cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR (clustered regularly interspaced palindromic repeats) pathway, requiring only the coexpression of a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA). The Cas9-sgRNA complex binds to DNA elements complementary to the sgRNA and causes a steric block that halts transcript elongation by RNA polymerase, resulting in the repression of the target gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1388, "text": "CRISPRi provides a simplified approach for rapid gene repression within 1-2 weeks. The method can also be adapted for high-throughput interrogation of genome-wide gene functions and genetic interactions, thus providing a complementary approach to RNA interference, which can be used in a wider variety of organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 823, "text": "More recently, a new system for genome engineering based on the bacterial CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats), was shown to have the potential to also regulate gene expression at both transcriptional and post-transcriptional level in a more specific way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25566532", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 322, "text": "CRISPR interference (CRISPRi), for targeted silencing of transcription in bacteria and human cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 873, "text": "RNA-seq analysis indicates that CRISPR interference (CRISPRi)-mediated transcriptional repression is highly specific.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23849981", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 1041, "text": "Our results establish that the CRISPR system can be used as a modular and flexible DNA-binding platform for the recruitment of proteins to a target DNA sequence, revealing the potential of CRISPRi as a general tool for the precise regulation of gene expression in eukaryotic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23849981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "CRISPR interference (CRISPRi) for sequence-specific control of gene expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "endSection": "title" }, { "offsetInBeginSection": 462, "offsetInEndSection": 709, "text": "We show that delivery of the CRISPRi system is successful and can specifically repress a reporter gene in recipient cells, thereby establishing a new tool for gene regulation across bacterial cells and potentially for bacterial population control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409531", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 805, "text": "This system, which we call CRISPR interference (CRISPRi), can efficiently repress expression of targeted genes in Escherichia coli, with no detectable off-target effects. CRISPRi can be used to repress multiple target genes simultaneously, and its effects are reversible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452860", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 572, "text": "We have recently described an RNA-based method, CRISPR interference (CRISPRi), for targeted silencing of transcription in bacteria and human cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR (clustered regularly interspaced palindromic repeats) pathway, requiring only the coexpression of a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1081, "text": "CRISPR interference (CRISPRi)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080438", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 251, "text": " Although the recent development of clustered regularly interspaced short palindromic repeats (CRISPR)-based screening approaches in mammalian cell culture ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080438", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1350, "text": "Clustered regularly interspaced palindromic repeats interference (CRISPRi)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26047700", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1117, "text": "E2f8, were most highly upregulated in miR-142-deficient cells. Clustered regularly interspaced short palindromic repeat interference-mediated (CRISPRi-mediated) silencing ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26098216", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 678, "text": " a new system for genome engineering based on the bacterial CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25566532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Sequence-specific control of gene expression on a genome-wide scale is an important approach for understanding gene functions and for engineering genetic regulatory systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24136345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Genetic screening based on loss-of-function phenotypes is a powerful discovery tool in biology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080438", "endSection": "abstract" } ] }, { "body": "Which type of cells is affected in Amyotrophic Lateral Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23197818", "http://www.ncbi.nlm.nih.gov/pubmed/24269728", "http://www.ncbi.nlm.nih.gov/pubmed/20846186", "http://www.ncbi.nlm.nih.gov/pubmed/22900096", "http://www.ncbi.nlm.nih.gov/pubmed/24971881", "http://www.ncbi.nlm.nih.gov/pubmed/22797053", "http://www.ncbi.nlm.nih.gov/pubmed/25384799", "http://www.ncbi.nlm.nih.gov/pubmed/23114367" ], "ideal_answer": [ "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder in which motor neurons are affected." ], "exact_answer": [ "Motor neurons" ], "type": "factoid", "id": "56c8274f5795f9a73e00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Activation of microglia, CNS resident immune cells, is a pathological hallmark of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder affecting motor neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24269728", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 376, "text": "We report that both small ubiquitin-like modifier (SUMO) 1 and SUMO2/3 modify ALS-linked SOD1 mutant proteins at lysine 75 in a motoneuronal cell line, the cell type affected in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971881", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 504, "text": "Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neurodegenerative disease characterized by ascending muscle weakness, atrophy and paralysis. Early muscle abnormalities that precede motor neuron loss in ALS may destabilize neuromuscular junctions, and we have previously demonstrated alterations in myogenic regulatory factor (MRF) expression in vivo and in the activation of myofiber-associated skeletal muscle satellite cells (SMSCs) in the mouse model of ALS (SOD1-G93A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22797053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease caused by selective loss of motor neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22900096", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 348, "text": "In the ALS motor neurons, TAR DNA-binding protein of 43 kDa (TDP-43) is dislocated from the nucleus to cytoplasm and forms inclusions, suggesting that loss of a nuclear function of TDP-43 may underlie the pathogenesis of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22900096", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 979, "text": "Development of an in vitro model system for ALS is expected to help in obtaining novel insights into disease mechanisms and discovery of therapeutics. We report the establishment of an in vitro FALS model from human embryonic stem cells overexpressing either a wild-type (WT) or a mutant SOD1 (G93A) gene and the evaluation of the phenotypes and survival of the spinal motor neurons (sMNs), which are the neurons affected in ALS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23197818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1 mutations suggest that neurodegeneration is a non-cell autonomous process where microglial cells influence disease progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25384799", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 297, "text": "In amyotrophic lateral sclerosis (ALS), affecting the motoneurones of the central nervous system (CNS), stem cell-based therapy aims to replace dying host motoneurones by transplantation of cells in disease-affected regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20846186", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 482, "text": "In amyotrophic lateral sclerosis, spasticity is traditionally thought to be the result of degeneration of the upper motor neurons in the cerebral cortex, although degeneration of other neuronal types, in particular serotonergic neurons, might also represent a cause of spasticity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23114367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Stem cell research raises hopes for incurable neurodegenerative diseases. In amyotrophic lateral sclerosis (ALS), affecting the motoneurones of the central nervous system (CNS), stem cell-based therapy aims to replace dying host motoneurones by transplantation of cells in disease-affected regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20846186", "endSection": "abstract" } ] }, { "body": "Is Achondroplasia associated with hearing loss?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3143244", "http://www.ncbi.nlm.nih.gov/pubmed/22628261", "http://www.ncbi.nlm.nih.gov/pubmed/9733026", "http://www.ncbi.nlm.nih.gov/pubmed/8456822", "http://www.ncbi.nlm.nih.gov/pubmed/22183904", "http://www.ncbi.nlm.nih.gov/pubmed/3240244", "http://www.ncbi.nlm.nih.gov/pubmed/8267016", "http://www.ncbi.nlm.nih.gov/pubmed/18328977" ], "ideal_answer": [ "Yes, there is hearing deficit in achondroplasia" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000130", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006309", "http://www.disease-ontology.org/api/metadata/DOID:4480", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034381", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046089", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006315", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006313", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006311", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054062", "http://www.disease-ontology.org/api/metadata/DOID:10003", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007605" ], "type": "yesno", "id": "52b2efcb4003448f55000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 800, "text": "A hearing screening program was performed to determine the prevalence of hearing loss and abnormal tympanometry in individuals with short-stature skeletal dysplasias attending a national meeting. Behavioral audiometry, otoacoustic emission testing, and tympanometry were used to assess hearing. Failed hearing screen was defined as hearing \u2265 35 dB at one or more frequencies or by \"fail\" on otoacoustic emissions. One hundred ten of 112 subjects completed the screening. 58 (51.8%) were children. Seventy-three (65.2%) had achondroplasia, 34 (30.4%) had one of 11 other diagnoses, and 5(4.4%) were undiagnosed. 25.8% of children failed hearing screening in one or both ears, while 46.3% of adults failed in one or both ears. 55.1% of adults and 25.0% of children with achondroplasia failed screening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22628261", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1520, "text": "Forty-four children had achondroplasia, and 31 had normal hearing in both ears (71%); 8 failed hearing screening in 1 ear (18%), and 3 in both ears (7%). Tympanometry was performed in 45 children, with normal tympanograms found in 21 (47%), bilateral abnormal tympanograms in 15 (33%), and unilateral abnormal tympanograms in 9 (20%). Fourteen children with achondroplasia had normal tympanograms (42%); 11 had bilateral abnormal tympanograms (33%); and 8 had unilateral abnormal tympanograms (24%). For those children without functioning tympanostomy tubes, there was a 9.5 times greater odds of hearing loss if there was abnormal tympanometry (P\u00a0=\u00a0.03).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22183904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 837, "text": "Achondroplasia (MIM 100800) is the most common non-lethal skeletal dysplasia. Its incidence is between one in 10,000 and one in 30,000. The phenotype is characterized by rhizomelic disproportionate short stature, enlarged head, midface hypoplasia, short hands and lordotic lumbar spine, associated with normal cognitive development. This autosomal-dominant disorder is caused by a gain-of-function mutation in the gene encoding the type 3 receptor for fibroblast growth factor (FGFR3); in more than 95% of cases, the mutation is G380R. The diagnosis is suspected on physical examination and confirmed by different age-related radiological features. Anticipatory and management care by a multidisciplinary team will prevent and treat complications, including cervical cord compression, conductive hearing loss and thoracolumbar gibbosity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18328977", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1213, "text": "The report includes information on otitis media, ventilation tubes, hearing loss, tonsillectomy, speech problems, tibial bowing and osteotomy, ventricular shunting, apnoea, cervicomedullary decompression, and neurological signs attributable to spinal stenosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9733026", "endSection": "abstract" }, { "offsetInBeginSection": 1270, "offsetInEndSection": 1483, "text": "We conclude that verbal comprehension is significantly impaired in children with achondroplasia. This partial deficiency is probably related to frequent middle ear infections and resulting conductive hearing loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8267016", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 512, "text": "In order to determine whether these morphologic changes are the cause of the hearing deficit in achondroplasia, audiometric studies and ENT evaluation were performed in eight of the nine patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456822", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1316, "text": "Audiograms were obtained in six of the nine achondroplastic subjects (two adults and four children). There was evidence of mixed hearing loss in the four children, but only of sensorineural hearing loss in the adults. We believe that the persistent hearing loss in achondroplasia is not due to sequelae of otitis media as some authors have suggested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3143244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The AA report a clinical and radiological study performed in 18 achondroplastic patients in order to achieve a nosological settlement of the otological impairments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3240244", "endSection": "abstract" } ] }, { "body": "Is the JNK pathway activated during liver regeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18671679", "http://www.ncbi.nlm.nih.gov/pubmed/21338344", "http://www.ncbi.nlm.nih.gov/pubmed/20207439", "http://www.ncbi.nlm.nih.gov/pubmed/21354444", "http://www.ncbi.nlm.nih.gov/pubmed/18382767", "http://www.ncbi.nlm.nih.gov/pubmed/16797887", "http://www.ncbi.nlm.nih.gov/pubmed/11709497", "http://www.ncbi.nlm.nih.gov/pubmed/15970430", "http://www.ncbi.nlm.nih.gov/pubmed/12668975", "http://www.ncbi.nlm.nih.gov/pubmed/23035542", "http://www.ncbi.nlm.nih.gov/pubmed/17762881", "http://www.ncbi.nlm.nih.gov/pubmed/20578144", "http://www.ncbi.nlm.nih.gov/pubmed/16242670" ], "ideal_answer": [ "Yes, the Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020935", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031099", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007254", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031098", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048670", "http://www.uniprot.org/uniprot/JNK_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004705", "http://www.uniprot.org/uniprot/JNK_SUBDO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008115" ], "type": "yesno", "id": "53455e0caeec6fbd0700000f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 130, "text": "analysis of the role of JNK signaling pathway in regulating cell proliferation and apoptosis of rat liver regeneration", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23035542", "endSection": "title" }, { "offsetInBeginSection": 1336, "offsetInEndSection": 1419, "text": "paths of JNK signaling pathway regulate cell proliferation and apoptosis in both LR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23035542", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 72, "text": "c-jun is not mandatory for mouse hepatocyte proliferation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21354444", "endSection": "title" }, { "offsetInBeginSection": 19, "offsetInEndSection": 111, "text": "Mice lacking c-jun in the liver display impaired regeneration after partial hepatectomy (PH)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21354444", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1002, "text": "initial activity of the JNK pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21338344", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 606, "text": "use of Drosophila for the study of regeneration ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21338344", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 950, "text": "Loss of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20578144", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 120, "text": "stress induced during intermittent selective clamping accelerates rat liver regeneration through JNK pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20207439", "endSection": "title" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1186, "text": "JNK2 promotes injury after mouse LT via the MPT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18671679", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 127, "text": "Jun N-terminal kinase 2 promotes graft injury via the mitochondrial permeability transition after mouse liver transplantation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18671679", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 101, "text": "add45beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18382767", "endSection": "title" }, { "offsetInBeginSection": 1354, "offsetInEndSection": 1481, "text": "basis for JNK suppression during liver regeneration and identify Gadd45beta as a potential therapeutic target in liver diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18382767", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 869, "text": " genetic inactivation of the JNK pathway results in impaired proliferation of fetal hepatoblasts in vitro and defective adult liver regeneration in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17762881", "endSection": "abstract" }, { "offsetInBeginSection": 53, "offsetInEndSection": 178, "text": "enhancement of the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase caused by partial hepatectomy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16797887", "endSection": "title" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1415, "text": " arsenite induced apoptosis in the hepatocytes in vivo, through the enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16797887", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 647, "text": "Jun N-terminal kinase and p38 MAPK, but not Akt, was altered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16242670", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 352, "text": "Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanical stress have not been determined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16242670", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1471, "text": " JNK, ERK and JAK2 inhibitors partially abrogated apoptosis and when used in combination reduced it to basal levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15970430", "endSection": "abstract" }, { "offsetInBeginSection": 1488, "offsetInEndSection": 1633, "text": "induction of CD40-mediated cholangiocyte apoptosis requires JAK2-mediated phosphorylation of STAT3 as well as sustained JNK1/2, ERK1/2 activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15970430", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 95, "text": "Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12668975", "endSection": "title" }, { "offsetInBeginSection": 4, "offsetInEndSection": 94, "text": "c-Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy (PH)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12668975", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 68, "text": "growth factors and cytokines are involved in liver regeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11709497", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 644, "text": "JAB1 (Jun activation domain-binding protein 1), a co-activator of AP-1, which is essential for liver regeneration, specifically interacts with intracellular HPO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11709497", "endSection": "abstract" } ] }, { "body": "Is STAT3 transcription factor regulated by mTORC1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24931163", "http://www.ncbi.nlm.nih.gov/pubmed/22055460", "http://www.ncbi.nlm.nih.gov/pubmed/26026060", "http://www.ncbi.nlm.nih.gov/pubmed/24302004", "http://www.ncbi.nlm.nih.gov/pubmed/23641065" ], "ideal_answer": [ "mTORC1 was found to regulate STAT3 activity in, at least, three ways: 1) after induction by IL6, 2) by direct phosphorylation during hypoxia, to promote HIF-1\u03b1 mRNA transcription, and 3) after activation by excess amino acids, which then positively regulate Notch1 expression through STAT3 activation." ], "exact_answer": "yes", "type": "yesno", "id": "56caf71b5795f9a73e00002d", "snippets": [ { "offsetInBeginSection": 907, "offsetInEndSection": 1250, "text": "Mechanistically, mTORC1 mediated IL-6-induced Stat3 activation in intestinal epithelial cells to stimulate the expression of downstream targets essential for cell proliferation and tissue regeneration. Therefore, mTORC1 signaling critically protects against inflammatory bowel disease through modulation of inflammation-induced Stat3 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26026060", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 952, "text": "we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1\u03b1 mRNA transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931163", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1071, "text": "Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24302004", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 366, "text": "Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22055460", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1189, "text": "Furthermore, we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1\u03b1 mRNA transcription. mTORC1 also regulates HIF-1\u03b1 synthesis on a translational level via co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whereas\u00a0HIF-1\u03b1 degradation remains unaffected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931163", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 368, "text": "Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22055460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22055460", "endSection": "title" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1072, "text": "Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24302004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24302004", "endSection": "title" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1363, "text": "Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPAR\u03b3, PPAR\u03b1, HIF1\u03b1, YY1\u2013PGC1\u03b1 and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23641065", "endSection": "abstract" } ] }, { "body": "How is mTORC1 involved in the regulation of heat stress?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21177857" ], "ideal_answer": [ "mTORC1 attenuates stress response by inhibiting cap-independent Hsp70 translation." ], "type": "summary", "id": "56cafca85795f9a73e000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "PI3K-mTORC1 attenuates stress response by inhibiting cap-independent Hsp70 translation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177857", "endSection": "title" }, { "offsetInBeginSection": 600, "offsetInEndSection": 702, "text": "stress-induced preferential translation of Hsp70 mRNA is negatively regulated by PI3K-mTORC1 signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177857", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 916, "text": "Conversely, Hsp70 synthesis is enhanced under the reduced PI3K-mTORC1 signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177857", "endSection": "abstract" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1233, "text": "Our findings imply a plausible mechanism for how persistent PI3K-mTORC1 signaling favors the development of age-related pathologies by attenuating stress resistance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177857", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 704, "text": "One prominent example is the selective translation of heat shock proteins (Hsps) under stress conditions. Although the transcriptional regulation of Hsp genes has been well established, neither the specific translation-promoting features nor the regulatory mechanism of the translation machinery have been clearly defined. Here we show that the stress-induced preferential translation of Hsp70 mRNA is negatively regulated by PI3K-mTORC1 signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "PI3K-mTORC1 attenuates stress response by inhibiting cap-independent Hsp70 translation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177857", "endSection": "title" } ] }, { "body": "List components of the CRSP/Med complex.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14759369", "http://www.ncbi.nlm.nih.gov/pubmed/12050112", "http://www.ncbi.nlm.nih.gov/pubmed/15175162", "http://www.ncbi.nlm.nih.gov/pubmed/9989412", "http://www.ncbi.nlm.nih.gov/pubmed/12509459", "http://www.ncbi.nlm.nih.gov/pubmed/24820420", "http://www.ncbi.nlm.nih.gov/pubmed/15195149", "http://www.ncbi.nlm.nih.gov/pubmed/10377381", "http://www.ncbi.nlm.nih.gov/pubmed/19571180", "http://www.ncbi.nlm.nih.gov/pubmed/11834832" ], "ideal_answer": [ "Mediator of RNA polymerase II transcription subunit 7\nMediator of RNA polymerase II transcription subunit 14\nMediator of RNA polymerase II transcription subunit 17\nMediator of RNA polymerase II transcription subunit 23\nMediator of RNA polymerase II transcription subunit 24\nMediator of RNA polymerase II transcription subunit 26\nMediator of RNA polymerase II transcription subunit 27" ], "exact_answer": [ [ "Mediator of RNA polymerase II transcription subunit 7" ], [ "Mediator of RNA polymerase II transcription subunit 14" ], [ "Mediator of RNA polymerase II transcription subunit 17" ], [ "Mediator of RNA polymerase II transcription subunit 23" ], [ "Mediator of RNA polymerase II transcription subunit 26" ], [ "Mediator of RNA polymerase II transcription subunit 27" ], [ "Mediator of RNA polymerase II transcription subunit 24" ] ], "concepts": [ "http://www.uniprot.org/uniprot/MED17_XENTR", "http://www.uniprot.org/uniprot/MED27_BOVIN", "http://www.uniprot.org/uniprot/MED7_PIG", "http://www.uniprot.org/uniprot/MED23_DANRE", "http://www.uniprot.org/uniprot/MED7_BOVIN", "http://www.uniprot.org/uniprot/MED7_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016329", "http://www.uniprot.org/uniprot/MED27_XENTR", "http://www.uniprot.org/uniprot/MED17_DANRE", "http://www.uniprot.org/uniprot/MED26_DANRE", "http://www.uniprot.org/uniprot/MED26_HUMAN", "http://www.uniprot.org/uniprot/MED17_BOVIN", "http://www.uniprot.org/uniprot/MED7_XENTR", "http://www.uniprot.org/uniprot/MED27_DANRE", "http://www.uniprot.org/uniprot/MED23_MOUSE", "http://www.uniprot.org/uniprot/MED27_HUMAN", "http://www.uniprot.org/uniprot/MED23_RAT", "http://www.uniprot.org/uniprot/MED27_PIG", "http://www.uniprot.org/uniprot/MED14_HUMAN", "http://www.uniprot.org/uniprot/MED7_DANRE", "http://www.uniprot.org/uniprot/MED26_MOUSE", "http://www.uniprot.org/uniprot/MED27_PONAB", "http://www.uniprot.org/uniprot/MED14_MOUSE", "http://www.uniprot.org/uniprot/MD27A_XENLA", "http://www.uniprot.org/uniprot/MED7_MOUSE", "http://www.uniprot.org/uniprot/MED17_CHICK", "http://www.uniprot.org/uniprot/MED26_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003067", "http://www.uniprot.org/uniprot/MED17_HUMAN", "http://www.uniprot.org/uniprot/MED7A_XENLA", "http://www.uniprot.org/uniprot/MED17_MOUSE", "http://www.uniprot.org/uniprot/MED27_MOUSE", "http://www.uniprot.org/uniprot/MED23_HUMAN", "http://www.uniprot.org/uniprot/MED24_HUMAN", "http://www.uniprot.org/uniprot/MED7B_XENLA", "http://www.uniprot.org/uniprot/MD27B_XENLA", "http://www.uniprot.org/uniprot/MED26_BOVIN" ], "type": "list", "id": "54e0dfa91388e8454a000018", "snippets": [ { "offsetInBeginSection": 622, "offsetInEndSection": 1322, "text": " Here we describe a new human factor, CRSP, that is required together with the TAF(II)s for transcriptional activation by Sp1. Purification of CRSP identifies a complex of approximate relative molecular mass 700,000 (M(r) approximately 700K) that contains nine subunits with M(r) values ranging from 33K to 200K. Cloning of genes encoding CRSP subunits reveals that CRSP33 is a homologue of the yeast mediator subunit Med7, whereas CRSP150 contains a domain conserved in yeast mediator subunit Rgr1. CRSP p200 is identical to the nuclear hormone-receptor co-activator subunit TRIP2/PBP. CRSPs 34, 77 and 130 are new proteins, but the amino terminus of CRSP70 is homologous to elongation factor TFIIS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9989412", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 905, "text": "CRSP contains unique subunits as well as polypeptides that are shared with other cofactor complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10377381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 432, "text": "The multi-subunit, human CRSP coactivator-also known as Mediator (Med)-regulates transcription by mediating signals between enhancer-bound factors (activators) and the core transcriptional machinery. Interestingly, different activators are known to bind distinct subunits within the CRSP/Med complex. We have isolated a stable, endogenous CRSP/Med complex (CRSP/Med2) that specifically lacks both the Med220 and the Med70 subunits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15175162", "endSection": "abstract" } ] }, { "body": "Patients of which disease could be treated by utilizing knowledge obtained from experiments suppressing TDP-43 toxicity in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23104007" ], "ideal_answer": [ "Amyotrophic lateral sclerosis (ALS).", "The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS " ], "exact_answer": [ "Amyotrophic lateral sclerosis (ALS)" ], "type": "factoid", "id": "5545e65bd355485447000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 382, "text": "Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease primarily affecting motor neurons. Mutations in the gene encoding TDP-43 cause some forms of the disease, and cytoplasmic TDP-43 aggregates accumulate in degenerating neurons of most individuals with ALS. Thus, strategies aimed at targeting the toxicity of cytoplasmic TDP-43 aggregates may be effective", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104007", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 1113, "text": "The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104007", "endSection": "abstract" } ] }, { "body": "Is calcium overload involved in the development of diabetic cardiomyopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22402252", "http://www.ncbi.nlm.nih.gov/pubmed/3850773", "http://www.ncbi.nlm.nih.gov/pubmed/8864644", "http://www.ncbi.nlm.nih.gov/pubmed/10359740", "http://www.ncbi.nlm.nih.gov/pubmed/3384188", "http://www.ncbi.nlm.nih.gov/pubmed/8761317" ], "ideal_answer": [ "Yes." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002118", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.biosemantics.org/jochem#4071295", "http://www.disease-ontology.org/api/metadata/DOID:9351" ], "type": "yesno", "id": "517139098ed59a060a000004", "snippets": [ { "offsetInBeginSection": 800, "offsetInEndSection": 1107, "text": "High-glucose treatment resulted in increased intracellular calcium ([Ca2+]i) which was mobilized to the mitochondria. Concomitant intra-mitochondrial calcium ([Ca2+]m) increase resulted in enhanced reactive oxygen and nitrogen species generation. These events led to mitochondrial dysfunction and apoptosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22402252", "endSection": "sections.0" }, { "offsetInBeginSection": 1788, "offsetInEndSection": 1965, "text": "The novel findings of the study reveal that high glucose induces apoptosis by both mitochondria-dependent and independent pathways via concomitant rise in intracellular calcium.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22402252", "endSection": "sections.0" }, { "offsetInBeginSection": 107, "offsetInEndSection": 224, "text": "Diabetes-induced myocardial dysfunction has been attributed, in part, to calcium overload within individual myocytes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8761317", "endSection": "sections.0" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1250, "text": "It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy;", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3850773", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: It has been suggested that intracellular Ca2+ overload in cardiac myocytes leads to the development of diabetic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10359740", "endSection": "sections.0" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1089, "text": "The results from the alloxan-rat model of diabetes support the view that membrane abnormalities with respect to Ca2+ handling may lead to the occurrence of intracellular Ca2+ overload and the development of diabetic cardiomyopathy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8864644", "endSection": "sections.0" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1403, "text": "It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy; however, a concentrated research effort is required to understand the primary biochemical lesion in the pathogenesis of cardiac dysfunction in diabetes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3850773", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "It has been suggested that the occurrence of an intracellular Ca2+ overload may result in the development of diabetic cardiomyopathy, which is associated with depletion of high-energy phosphate stores and a derangement of ultrastructure and cardiac dysfunction.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3384188", "endSection": "sections.0" } ] }, { "body": "What is the mechanism of viroid replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9356244", "http://www.ncbi.nlm.nih.gov/pubmed/18370255", "http://www.ncbi.nlm.nih.gov/pubmed/15448723", "http://www.ncbi.nlm.nih.gov/pubmed/25287502", "http://www.ncbi.nlm.nih.gov/pubmed/1717335", "http://www.ncbi.nlm.nih.gov/pubmed/21994552", "http://www.ncbi.nlm.nih.gov/pubmed/3860809", "http://www.ncbi.nlm.nih.gov/pubmed/9601006", "http://www.ncbi.nlm.nih.gov/pubmed/6760914", "http://www.ncbi.nlm.nih.gov/pubmed/11907231", "http://www.ncbi.nlm.nih.gov/pubmed/7231549", "http://www.ncbi.nlm.nih.gov/pubmed/18190946", "http://www.ncbi.nlm.nih.gov/pubmed/17438124", "http://www.ncbi.nlm.nih.gov/pubmed/7747427" ], "ideal_answer": [ "The replication of many viral and subviral pathogens as well as the amplification of certain cellular genes proceeds via a rolling circle mechanism. Viroid replication occurs via a rolling circle mechanism using either a symmetric or asymmetric pathway in three steps, RNA transcription, processing and ligation. Replication of these minimal genomes, composed exclusively by a circular RNA of 246-401 nt, occurs in the nucleus (family Pospiviroidae) or in the chloroplast (family Avsunviroidae) by an RNA-based rolling-circle mechanism with three steps: (1) synthesis of longer-than-unit strands catalyzed by host DNA-dependent RNA polymerases recruited and redirected to transcribe RNA templates, (2) cleavage to unit-length, which in family Avsunviroidae is mediated by hammerhead ribozymes, and (3) circularization through an RNA ligase or autocatalytically." ], "exact_answer": [ "rolling cycle" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014772" ], "type": "factoid", "id": "56f3faed09dd18d46b000002", "snippets": [ { "offsetInBeginSection": 178, "offsetInEndSection": 505, "text": "Together with the specific alpha-amanitin sensitivity of viroid replication observed in vivo, these findings suggest that viroids replicate by an entirely novel mechanism in which infecting viroid RNA molecules are copied by the host enzyme which is normally responsible for the synthesis of nuclear precursors to messenger RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7231549", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 353, "text": "In vitro synthesis of complementary RNA produces distinct transcripts larger than unit length thus reflecting the in vivo mechanism of viroid replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6760914", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 979, "text": "This mechanism could account for the origin of viroids and also RNA viruses, whereby modules of genetic information may have undergone repeated exchange between RNA pathogens and the RNA of their hosts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3860809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The replication of many viral and subviral pathogens as well as the amplification of certain cellular genes proceeds via a rolling circle mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9601006", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1458, "text": "Viroid replication occurs via a rolling circle mechanism using either a symmetric or asymmetric pathway in three steps, RNA transcription, processing and ligation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15448723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Viroids replicate through a rolling circle mechanism that is exclusively RNA dependent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18190946", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 615, "text": "Subsequently, an in vitro selection procedure based on a model rolling circle replication assay was developed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18190946", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 643, "text": "Replication of these minimal genomes, composed exclusively by a circular RNA of 246-401 nt, occurs in the nucleus (family Pospiviroidae) or in the chloroplast (family Avsunviroidae) by an RNA-based rolling-circle mechanism with three steps: (1) synthesis of longer-than-unit strands catalyzed by host DNA-dependent RNA polymerases recruited and redirected to transcribe RNA templates, (2) cleavage to unit-length, which in family Avsunviroidae is mediated by hammerhead ribozymes, and (3) circularization through an RNA ligase or autocatalytically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18370255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Viroid replication: rolling-circles, enzymes and ribozymes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21994552", "endSection": "title" }, { "offsetInBeginSection": 290, "offsetInEndSection": 920, "text": "Viroid replication proceeds through an RNA-based rolling-circle mechanism with three steps that, with some variations, operate in both polarity strands: i) synthesis of longer-than-unit strands catalyzed by either the nuclear RNA polymerase II or a nuclear-encoded chloroplastic RNA polymerase, in both instances redirected to transcribe RNA templates, ii) cleavage to unit-length, which in the family Avsunviroidae is mediated by hammerhead ribozymes embedded in both polarity strands, while in the family Pospiviroidae the oligomeric RNAs provide the proper conformation but not the catalytic activity, and iii) circularization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21994552", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 333, "text": "Viroid replication is entirely dependent on host transcription machinery, and their replication/accumulation in the infected cells can activate RNA silencing-a host defense mechanism that targets the viroid itself. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287502", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1610, "text": "Viroid replication occurs via a rolling circle mechanism using either a symmetric or asymmetric pathway in three steps, RNA transcription, processing and ligation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15448723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Viroids replicate via a rolling circle mechanism, and cleavage/ligation requires extensive rearrangement of the highly base-paired native structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17438124", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 975, "text": "Viroids are not translated; they are replicated by a host enzyme (or enzymes) (probably RNA polymerase II) via oligomeric RNA intermediates by a rolling circle mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1717335", "endSection": "abstract" }, { "offsetInBeginSection": 1720, "offsetInEndSection": 2023, "text": "We hypothesize that the intramolecular self-ligation which produces circular conformers may contribute to the circularization step of the rolling circle replication, while the intermolecular non-enzymatic ligation is a potential mechanism for the sequence reassortment of viroids and viroid-like species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9356244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Hepatitis delta virus (HDV) contains a viroid-like circular RNA that is presumed to replicate via a rolling circle replication mechanism mediated by cellular RNA polymerases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11907231", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1457, "text": "Viroid replication occurs via a rolling circle mechanism using either a symmetric or asymmetric pathway in three steps, RNA transcription, processing and ligation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15448723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Viroids replicate through a rolling circle mechanism that is exclusively RNA dependent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18190946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": " Hepatitis delta virus (HDV) contains a viroid-like circular RNA that is presumed to replicate via a rolling circle replication mechanism mediated by cellular RNA polymerases. However, the exact mechanism of rolling circle replication for HDV RNA and viroids is not clear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11907231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": " Viroids replicate through a rolling circle mechanism that is exclusively RNA dependent. In this study, we initially revisited the determination of the replication initiation sites of peach latent mosaic viroid (PLMVd).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18190946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Hepatitis delta virus (HDV) contains a viroid-like circular RNA that is presumed to replicate via a rolling circle replication mechanism mediated by cellular RNA polymerases. However, the exact mechanism of rolling circle replication for HDV RNA and viroids is not clear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11907231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Viroids replicate through a rolling circle mechanism that is exclusively RNA dependent. In this study, we initially revisited the determination of the replication initiation sites of peach latent mosaic viroid (PLMVd).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18190946", "endSection": "abstract" } ] }, { "body": "Which mitochondrial genes are regulated by thyroid hormone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1331777", "http://www.ncbi.nlm.nih.gov/pubmed/12225634", "http://www.ncbi.nlm.nih.gov/pubmed/7763274" ], "ideal_answer": [ "subunit 6 of ATP synthase, ATPase-6, mitochondrial II and III subunits of cytochrome-c oxidase, NADH dehydrogenase subunit 3" ], "exact_answer": [ [ "subunit 6 of ATP synthase", "ATPase-6" ], [ "mitochondrial II and III subunits of cytochrome-c oxidase" ], [ "NADH dehydrogenase subunit 3", "ND3" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050259" ], "type": "list", "id": "517539e68ed59a060a000028", "snippets": [ { "offsetInBeginSection": 76, "offsetInEndSection": 244, "text": "We used a polymerase chain reaction (PCR)-based mRNA differential display (DD) analysis to obtain a profile of thyroid hormone-responsive genes in osteoblast-like cells", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12225634", "endSection": "sections.0" }, { "offsetInBeginSection": 503, "offsetInEndSection": 649, "text": "At the 2-hour time point, 1 true-positive novel clone was identified and shown to be the mitochondrial gene, subunit 6 of ATP synthase (ATPase-6).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12225634", "endSection": "sections.0" }, { "offsetInBeginSection": 124, "offsetInEndSection": 549, "text": "We studied the coordination of the two genomes by measuring transcript levels for nuclear (IV, Va, and VIc) and mitochondrial (II and III) subunits of cytochrome-c oxidase after altering the mitochondrial content of rat muscle and liver by altering the thyroid state of the animals. Tissue levels of these mRNAs were generally decreased in hypothyroid animals and were up-regulated again after thyroid hormone (T3) treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1331777", "endSection": "sections.0" }, { "offsetInBeginSection": 186, "offsetInEndSection": 335, "text": "Following this procedure, we now report the identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) gene as target of thyroid hormone.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7763274", "endSection": "sections.0" }, { "offsetInBeginSection": 412, "offsetInEndSection": 582, "text": "Sequencing and electrophoretic mobility shift assays confirmed the presence of a thyroid hormone receptor (TR)/c-erbA specific binding site in the mitochondrial ND3 gene.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7763274", "endSection": "sections.0" } ] }, { "body": "Mutation of which gene is associated with McLeod syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11099667", "http://www.ncbi.nlm.nih.gov/pubmed/11761473", "http://www.ncbi.nlm.nih.gov/pubmed/19909712", "http://www.ncbi.nlm.nih.gov/pubmed/11562915", "http://www.ncbi.nlm.nih.gov/pubmed/1734714", "http://www.ncbi.nlm.nih.gov/pubmed/24098554", "http://www.ncbi.nlm.nih.gov/pubmed/23943810", "http://www.ncbi.nlm.nih.gov/pubmed/17300882", "http://www.ncbi.nlm.nih.gov/pubmed/21145924", "http://www.ncbi.nlm.nih.gov/pubmed/10846875", "http://www.ncbi.nlm.nih.gov/pubmed/12899725", "http://www.ncbi.nlm.nih.gov/pubmed/8004674", "http://www.ncbi.nlm.nih.gov/pubmed/17277857", "http://www.ncbi.nlm.nih.gov/pubmed/17469188", "http://www.ncbi.nlm.nih.gov/pubmed/12243006", "http://www.ncbi.nlm.nih.gov/pubmed/10651848", "http://www.ncbi.nlm.nih.gov/pubmed/3334897", "http://www.ncbi.nlm.nih.gov/pubmed/18167163", "http://www.ncbi.nlm.nih.gov/pubmed/16344536", "http://www.ncbi.nlm.nih.gov/pubmed/17870653", "http://www.ncbi.nlm.nih.gov/pubmed/10930599", "http://www.ncbi.nlm.nih.gov/pubmed/8634708", "http://www.ncbi.nlm.nih.gov/pubmed/10426139", "http://www.ncbi.nlm.nih.gov/pubmed/19040496", "http://www.ncbi.nlm.nih.gov/pubmed/22383943", "http://www.ncbi.nlm.nih.gov/pubmed/12823753", "http://www.ncbi.nlm.nih.gov/pubmed/11746618", "http://www.ncbi.nlm.nih.gov/pubmed/11703337", "http://www.ncbi.nlm.nih.gov/pubmed/24179763", "http://www.ncbi.nlm.nih.gov/pubmed/16314760", "http://www.ncbi.nlm.nih.gov/pubmed/10882128", "http://www.ncbi.nlm.nih.gov/pubmed/8619554", "http://www.ncbi.nlm.nih.gov/pubmed/11261514", "http://www.ncbi.nlm.nih.gov/pubmed/17302777" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3073", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/XK" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3073", "o": "http://www.dbpedia.org/resource/McLeod_syndrome" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/XK", "o": "XK" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3073", "o": "McLeod syndrome" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3074", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/XK" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3074", "o": "McLeod syndrome with neuroacanthosis" } ], "ideal_answer": [ "Mutation of XK gene is associated with McLeod syndrome. The XK gene is an X-chromosomal gene. The McLeod phenotype is derived from various forms of XK gene defects that result in the absence of XK protein, and is defined hematologically by the absence of Kx antigen, weakening of Kell system antigens, and red cell acanthocytosis." ], "exact_answer": [ "XK" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "factoid", "id": "531464a6e3eabad021000014", "snippets": [ { "offsetInBeginSection": 247, "offsetInEndSection": 343, "text": "The diagnosis of MLS was confirmed by genetic testing showing a hemizygous mutation of XK gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23943810", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 616, "text": "We performed a comprehensive mutation screen of VPS13A and XK, the gene responsible for ChAc and MLS, respectively, in 85 mood disorder subjects and XK in 86 schizophrenia subjects and compared the variants to 100 or more control alleles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21145924", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 296, "text": "We hypothesized that because the XK gene is X-linked, it would be easy to identify spontaneously arising red cells with a phenotype resembling the McLeod syndrome, which results from inherited XK mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19909712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Identification and characterization of a novel XK splice site mutation in a patient with McLeod syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19040496", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 292, "text": "McLeod syndrome is caused by mutations in the XK gene whose product is expressed at the red blood cell (RBC) surface but whose function is currently unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19040496", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 1016, "text": "The responsible XK mutation was characterized at the mRNA level by reverse transcription-polymerase chain reaction (PCR), identified by genomic DNA sequencing, and verified by allele-specific PCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19040496", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1419, "text": "A novel XK splice site mutation (IVS1-1G>A) has been identified in a McLeod patient who has developed hematologic, neuromuscular, and neurologic symptoms. This is the first reported example of a XK point mutation affecting the 3' acceptor splice site of Intron 1, and it was demonstrated that this mutation indeed induces aberrant splicing of XK RNA and lack of XK protein at the RBC membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19040496", "endSection": "abstract" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1686, "text": "The detailed characterization at the molecular biology level of this novel XK splice site mutation associated with the clinical description of the patient contributes to a better understanding of the phenotype-genotype correlation in the McLeod syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19040496", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 412, "text": "Genetic test revealed a R133X mutation of the XK gene, confirming the McLeod syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17870653", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 593, "text": "Molecular genetic analysis revealed a small deletion in the XK gene (938-942delCTCTA), which has been already described in a North American patient of Anglo-Saxon descent and a Japanese family, presenting with seizures, muscle atrophy or chorea yet absence of psychiatric features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17469188", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 416, "text": "A variety of mutations have been found in the responsible gene (XK) including single nonsense and missense mutations, nucleotide mutations at or near the splice junctions of introns of XK, and different deletion mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302777", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1182, "text": "The first case had been authenticated as a genuine McLeod both by serology and by genotyping (R222G missense mutation) and the second case had a mutation in XK (IVS2+5G>A) and by serology exhibited very weak Kx antigen and no detectable Kell antigens, except extremely low k antigen by adsorption-elution technique. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302777", "endSection": "abstract" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1444, "text": "Despite documented McLeod phenotype on RBCs, and identified mutations of XK, neurologic and other clinical findings were minimal at ages expected to manifest MLS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302777", "endSection": "abstract" }, { "offsetInBeginSection": 1457, "offsetInEndSection": 1584, "text": "The different XK mutations may have different effects upon the XK gene product and thus may account for the variable phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17302777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17300882", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "The McLeod phenotype is derived from various forms of XK gene defects that result in the absence of XK protein, and is defined hematologically by the absence of Kx antigen, weakening of Kell system antigens, and red cell acanthocytosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17300882", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 667, "text": "MLS is an X-linked multi-system disorder caused by absence of XK alone, or when the disorder is caused by large deletions, it may be accompanied with Duchenne muscular dystrophy (DMD), chronic granulomatous disease (CYBB), retinitis pigmentosa (RPGR), and ornithine transcarbamylase deficiency (OTC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17300882", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1007, "text": "Case 1 has greater than 1.12 million base-pairs (mb) deletion around the XK locus with 7 genes affected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17300882", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 517, "text": "The McLeod Syndrome, one of the core neuroacanthocytosis syndromes, is a rare X-linked disorder caused by mutations of the XK gene, an X-chromosomal gene of unknown function characterized by haemopoietic abnormalities and late-onset neurological and muscular defects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17277857", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 286, "text": "Linkage analysis and sequencing revealed a XK gene mutation (McLeod syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16344536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "McLeod syndrome: life-long neuropsychiatric disorder due to a novel mutation of the XK gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314760", "endSection": "title" }, { "offsetInBeginSection": 493, "offsetInEndSection": 647, "text": "DNA studies demonstrated a single-base deletion at position 172 in exon 1 of the XK gene, giving rise to a premature stop codon at position 129 in exon 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "McLeod syndrome resulting from a novel XK mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12899725", "endSection": "title" }, { "offsetInBeginSection": 308, "offsetInEndSection": 368, "text": "MLS is caused by hemizygosity for mutations in the XK gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12899725", "endSection": "abstract" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1321, "text": "The patient's daughters had two populations of red cells, consistent with them being heterozygous for an XK0 allele. The molecular basis of MLS in this family is a novel mutation consisting of a 7453-bp deletion that includes exon 2 of the XK gene. This confirms that the patient's 7-year-old grandson, who is currently asymptomatic, also has the XK0 allele and is therefore likely to develop MLS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12899725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12823753", "endSection": "title" }, { "offsetInBeginSection": 818, "offsetInEndSection": 930, "text": "XK gene sequence analysis revealed a missense mutation in exon 3 (E327K). WBC XK RNA levels were not decreased. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12823753", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1748, "text": "Known disease-causing XK gene mutations comprised deletions, nonsense, or splice-site mutations predicting absent or truncated XK protein devoid of the Kell-protein binding site. Although the E327K missense mutation was associated with the immunohematologic characteristics of McLeod syndrome, the mutated XK protein seemed to be largely functional. These findings contribute to the understanding of the physiology of XK and Kell proteins, and the pathogenetic mechanisms of acanthocytosis, myopathy, and striatal neurodegeneration in McLeod syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12823753", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 489, "text": "With the discovery of their molecular bases, mutations of the X-linked gene XK and autosomal recessive mutations of the gene coding for chorein, respectively, the two phenotypes can now be differentiated and extend the diagnostic spectrum in patients presenting with chorea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12243006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unknown function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11761473", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 454, "text": "Fifteen different XK mutations were found, nine of which were novel, including the one of the eponymous case McLeod. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11761473", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 492, "text": "We present six males (aged 29 to 60 years), with proven XK mutations, to discuss the chorea associated with McLeod syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11746618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "A spontaneous novel XK gene mutation in a patient with McLeod syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11703337", "endSection": "title" }, { "offsetInBeginSection": 245, "offsetInEndSection": 352, "text": "Investigation of the patient's XK gene revealed a novel TGG- to-TAG transition at position 1023 in exon 3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11703337", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 234, "text": "It is caused by mutations of the XK gene encoding the XK protein, a putative membrane transport protein of yet unknown function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11562915", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 521, "text": "Here, we present an immunohistochemical study in skeletal muscle of normal controls and a McLeod patient with a XK gene point mutation (C977T) using affinity-purified antibodies against XK and Kell proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11562915", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The McLeod syndrome is an X-linked disorder caused by mutations of the XK gene encoding the XK protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11261514", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 520, "text": "We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11261514", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1261, "text": "he XK gene had a point mutation in the donor splice site of intron 1 (G>C). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11099667", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 486, "text": "Direct sequencing of the PCR-amplified genomic DNA revealed the mutation was a single C-nucleotide insertion at codon 151 in exon 2 of the XK gene, which resulted in a 3'-frameshift.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10930599", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 220, "text": "It is caused by XK gene defects and may include large deletions in the Xp21 region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10651848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "We report a novel mutation in the XK gene (XK) in a Japanese patient with McLeod syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10426139", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 399, "text": "The expression level of all the Kell antigens in erythrocyte was decreased and molecular analysis revealed a single-base (T) deletion at the nucleotide position 1095 in XK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10426139", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 719, "text": "The gene termed SRPX (sushi-repeat-containing protein, x chromosome) is deleted in an RP patient who also suffers from chronic granulomatous disease and McLeod syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8634708", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 480, "text": " The mRNA expression pattern of one of them, designated as XK, correlates closely to the McLeod phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8004674", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 745, "text": "Nucleotide sequence analysis of XK from two unrelated McLeod patients has identified point mutations at conserved splice donor and acceptor sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8004674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1734714", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Gene deletion in a patient with chronic granulomatous disease and McLeod syndrome: fine mapping of the Xk gene locus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3334897", "endSection": "title" } ] }, { "body": "Is RIP1 (RIP-1) part of the necrosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22421439", "http://www.ncbi.nlm.nih.gov/pubmed/23612963", "http://www.ncbi.nlm.nih.gov/pubmed/24059293", "http://www.ncbi.nlm.nih.gov/pubmed/23898178", "http://www.ncbi.nlm.nih.gov/pubmed/23162759", "http://www.ncbi.nlm.nih.gov/pubmed/22016814", "http://www.ncbi.nlm.nih.gov/pubmed/22817896", "http://www.ncbi.nlm.nih.gov/pubmed/22033613", "http://www.ncbi.nlm.nih.gov/pubmed/21749897", "http://www.ncbi.nlm.nih.gov/pubmed/22666585", "http://www.ncbi.nlm.nih.gov/pubmed/24098568", "http://www.ncbi.nlm.nih.gov/pubmed/22576661", "http://www.ncbi.nlm.nih.gov/pubmed/21890409" ], "ideal_answer": [ "Yes, RIP1 is part of the necrosome." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001906", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053422", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008219", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070265", "http://www.uniprot.org/uniprot/RIPK1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009336", "http://www.uniprot.org/uniprot/RIPK1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097300" ], "type": "yesno", "id": "532bfd15d6d3ac6a34000017", "snippets": [ { "offsetInBeginSection": 1179, "offsetInEndSection": 1272, "text": "formation of a different necrosome whose components, besides RIP1 and RIP3, are still unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033613", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 975, "text": "necrosome complex consisting of RIP1, RIP3, FADD, caspase-8 and cFLIP(L).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016814", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 673, "text": "assembly of a supramolecular complex containing the receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3) that delivers a pronecrotic signal. Such complex has recently been dubbed necrosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749897", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 213, "text": "Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24098568", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 268, "text": "The phosphorylation of RIP1 and RIP3 is critical for assembly of the necrosome,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24059293", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 527, "text": "RIP1-RIP3 \"necrosome\" complex ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23898178", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 400, "text": "RIP1 and RIP3 mediate necrosome aggregation leading to the formation of amyloid-like signaling complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23612963", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 894, "text": "Formation of the RIP1/RIP3 complex (called necrosome) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23162759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 24, "text": "The RIP1/RIP3 necrosome ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22817896", "endSection": "title" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1001, "text": "Rip1-Rip3 death complex (necrosome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22576661", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 663, "text": "he 'necrosome', that includes receptor-interacting protein (RIP)1, RIP3 and caspase-8. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21890409", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 998, "text": "RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3) leading to programmed necrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22666585", "endSection": "abstract" } ] }, { "body": "Which is the molecular target of the immunosuppressant drug Rapamycin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14508096", "http://www.ncbi.nlm.nih.gov/pubmed/15901852", "http://www.ncbi.nlm.nih.gov/pubmed/22442756", "http://www.ncbi.nlm.nih.gov/pubmed/18451231", "http://www.ncbi.nlm.nih.gov/pubmed/23994756", "http://www.ncbi.nlm.nih.gov/pubmed/15627018", "http://www.ncbi.nlm.nih.gov/pubmed/23301832", "http://www.ncbi.nlm.nih.gov/pubmed/15163844", "http://www.ncbi.nlm.nih.gov/pubmed/18980246", "http://www.ncbi.nlm.nih.gov/pubmed/17728765", "http://www.ncbi.nlm.nih.gov/pubmed/17041625", "http://www.ncbi.nlm.nih.gov/pubmed/23261661" ], "ideal_answer": [ "The molecular target of Rapamycin is mTOR" ], "exact_answer": [ "mTOR" ], "concepts": [ "http://www.uniprot.org/uniprot/TOR_ARATH", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032006", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031929", "http://www.uniprot.org/uniprot/TOR_DICDI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020123", "http://www.biosemantics.org/jochem#4274961", "http://www.uniprot.org/uniprot/TOR_ORYSJ", "http://www.uniprot.org/uniprot/TOR_DROME" ], "type": "factoid", "id": "53124bdae3eabad02100000b", "snippets": [ { "offsetInBeginSection": 1170, "offsetInEndSection": 1205, "text": "molecular target of rapamycin (mTOR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23994756", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 679, "text": "molecular target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23301832", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 41, "text": "molecular target of rapamycin (mTOR) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261661", "endSection": "abstract" }, { "offsetInBeginSection": 1839, "offsetInEndSection": 1875, "text": "molecular target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22442756", "endSection": "abstract" }, { "offsetInBeginSection": 1363, "offsetInEndSection": 1399, "text": "molecular target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18980246", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 92, "text": "molecular target of rapamycin (mTOR) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18451231", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 40, "text": "molecular target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17728765", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 363, "text": "the molecular Target Of Rapamycin, TOR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17041625", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1573, "text": "molecular target of rapamycin (mTOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15901852", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 49, "text": "molecular target of rapamycin (mTOR", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15627018", "endSection": "title" }, { "offsetInBeginSection": 1930, "offsetInEndSection": 1967, "text": "molecular target of rapamycin (mTOR) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15163844", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 41, "text": "molecular target of rapamycin (mTOR),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14508096", "endSection": "abstract" } ] }, { "body": "Is the protein KCNQ2 associated with idiopathic epilepsy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10323247", "http://www.ncbi.nlm.nih.gov/pubmed/16302872", "http://www.ncbi.nlm.nih.gov/pubmed/18625963", "http://www.ncbi.nlm.nih.gov/pubmed/23182620", "http://www.ncbi.nlm.nih.gov/pubmed/21937445", "http://www.ncbi.nlm.nih.gov/pubmed/14640909", "http://www.ncbi.nlm.nih.gov/pubmed/12458027", "http://www.ncbi.nlm.nih.gov/pubmed/17044971", "http://www.ncbi.nlm.nih.gov/pubmed/19464834", "http://www.ncbi.nlm.nih.gov/pubmed/19818940", "http://www.ncbi.nlm.nih.gov/pubmed/9677360", "http://www.ncbi.nlm.nih.gov/pubmed/18246739", "http://www.ncbi.nlm.nih.gov/pubmed/10446744", "http://www.ncbi.nlm.nih.gov/pubmed/16260777", "http://www.ncbi.nlm.nih.gov/pubmed/18640800", "http://www.ncbi.nlm.nih.gov/pubmed/10363917", "http://www.ncbi.nlm.nih.gov/pubmed/10716662", "http://www.ncbi.nlm.nih.gov/pubmed/10472660" ], "ideal_answer": [ "Yes, sequence variations of the KCNQ2 gene may contribute to the etiology of idiopathic epilepsy" ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/KCNQ2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051658", "http://www.uniprot.org/uniprot/KCNQ2_RAT" ], "type": "yesno", "id": "56c30ce99d3e5f1412000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "Juvenile idiopathic epilepsy (JIE) in Arabian foals resembles benign-familial neonatal convulsion (BFNC) syndrome, a rare idiopathic epilepsy of new-born humans. BFNC syndrome exhibits genetic heterogeneity, as has been hypothesised to occur in Arabian foals, and is known to be caused by mutations in the voltage-gated potassium channel subunit KCNQ2 and KCNQ3 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182620", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1651, "text": "They also demonstrate that sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common IE syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464834", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 155, "text": "The underlying genetic abnormalities of rare familial idiopathic epilepsy have been identified, such as mutation in KCNQ2, a K(+) channel gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18640800", "endSection": "abstract" }, { "offsetInBeginSection": 1591, "offsetInEndSection": 1711, "text": "Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18625963", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 499, "text": "This paper summarizes recent findings concerning sodium (SCN1A) and potassium channel (KCNQ2 and KCNQ3) dysfunctions in the pathogenesis of rare and common idiopathic epilepsies (IE). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Mutations in the SCN1A gene are found in up to 80% of individuals with severe myoclonic epilepsy of infancy (SMEI), and mutations in KCNQ2 and KCNQ3 were identified in benign familial neonatal convulsions (BFNC) as well as in single families with Rolandic epilepsy (RE) and idiopathic generalized epilepsies (IGE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464834", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 549, "text": "The involvement of KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) in a benign idiopathic neonatal epilepsy, KCNQ4 (Kv7.4) in a form of congenital deafness, and the discovery that neuronal KCNQ heteromultimers were among the molecular substrates of M-channels, resulted in a high level of interest for potential drug development strategies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14640909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Mutations in the SCN1A gene are found in up to 80% of individuals with severe myoclonic epilepsy of infancy (SMEI), and mutations in KCNQ2 and KCNQ3 were identified in benign familial neonatal convulsions (BFNC) as well as in single families with Rolandic epilepsy (RE) and idiopathic generalized epilepsies (IGE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464834", "endSection": "abstract" }, { "offsetInBeginSection": 1367, "offsetInEndSection": 1540, "text": "The functional interaction between KCNQ2 and KCNQ3 provides a framework for understanding how mutations in either channel can cause a form of idiopathic generalized epilepsy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9677360", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 295, "text": "Mutations in KCNQ2- or KCNQ3-encoding genes cause benign familiar neonatal convulsions (BFNCs), a rare autosomal-dominant idiopathic epilepsy of the newborn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16260777", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 336, "text": "Mutations in KCNQ2 or KCNQ3 that reduce the M-current are responsible for benign familial neonatal seizures, a rare autosomal dominant idiopathic epilepsy of the newborn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19818940", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 662, "text": "These include benign familial neonatal convulsions due to mutations in KCNQ2 or KCNQ3, generalized epilepsy with febrile seizures plus due to mutations in SCN1A, SCN2A, SCN1B, and GABRG2, autosomal-dominant juvenile myoclonic epilepsy (JME) due to a mutation in GABRA1 and mutations in CLCN2 associated with several IGE sub-types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16302872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18625963", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Role of KCNQ2 and KCNQ3 genes in juvenile idiopathic epilepsy in Arabian foals", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182620", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Mutations in the voltage gated potassium channel gene KCNQ2 and the homologous gene KCNQ3 have been found to cause a rare monogenic subtype of idiopathic generalized epilepsy, the benign familial neonatal convulsions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10363917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Role of KCNQ2 and KCNQ3 genes in juvenile idiopathic epilepsy in Arabian foals.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182620", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18625963", "endSection": "title" } ] }, { "body": "PBT2 has been tested for which disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21797865", "http://www.ncbi.nlm.nih.gov/pubmed/18953111", "http://www.ncbi.nlm.nih.gov/pubmed/21504115", "http://www.ncbi.nlm.nih.gov/pubmed/21739113", "http://www.ncbi.nlm.nih.gov/pubmed/20164561", "http://www.ncbi.nlm.nih.gov/pubmed/18672400", "http://www.ncbi.nlm.nih.gov/pubmed/18625454", "http://www.ncbi.nlm.nih.gov/pubmed/16370917", "http://www.ncbi.nlm.nih.gov/pubmed/22592705", "http://www.ncbi.nlm.nih.gov/pubmed/20545360", "http://www.ncbi.nlm.nih.gov/pubmed/22747493", "http://www.ncbi.nlm.nih.gov/pubmed/21232050", "http://www.ncbi.nlm.nih.gov/pubmed/19742190", "http://www.ncbi.nlm.nih.gov/pubmed/22403554" ], "ideal_answer": [ "PBT2 has been tested for treatment of Alzheimer's disease." ], "exact_answer": [ "Alzheimer's disease" ], "type": "factoid", "id": "54fc91e96ad7dcbc12000001", "snippets": [ { "offsetInBeginSection": 2876, "offsetInEndSection": 2998, "text": "PBT2 improved cognition in a phase II clinical trial with AD patients, and further clinical testing is currently underway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22747493", "endSection": "abstract" }, { "offsetInBeginSection": 2223, "offsetInEndSection": 2402, "text": "In the second trial a successor compound, PBT2, was compared with placebo in 78 participants with mild Alzheimer's dementia; all were included in the intention-to-treat analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22592705", "endSection": "abstract" }, { "offsetInBeginSection": 3614, "offsetInEndSection": 3795, "text": "The second trial of PBT2 was more rigorously conducted and showed that after 12 weeks this compound appeared to be safe and well tolerated in people with mild Alzheimer's dementia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22592705", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 830, "text": "The purpose of this mini-review is to highlight the emerging notion that metal chaperones, such as PBT2 (Prana Biotechnology), modulate a variety of critical pathways affecting key aspects of the AD cascade to provide a more \"holistic\" approach to the treatment of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The Alzheimer's therapeutic PBT2 promotes amyloid-\u03b2 degradation and GSK3 phosphorylation via a metal chaperone activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21797865", "endSection": "title" }, { "offsetInBeginSection": 157, "offsetInEndSection": 271, "text": "The leading compound in this class of therapeutic, PBT2, improved cognition in a clinical trial with AD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21797865", "endSection": "abstract" }, { "offsetInBeginSection": 1305, "offsetInEndSection": 1477, "text": "Intracellular translocation of Zn and Cu via the metal chaperone activity of PBT2 may be an important mechanism by which PBT2 improves cognitive function in people with AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21797865", "endSection": "abstract" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1208, "text": "Metalloproteinase modifiers such as PBT2 may be useful AD therapies, but current evidence gives no support to their immediate use in pre-symptomatic AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21739113", "endSection": "abstract" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1401, "text": "The most advanced of these strategies is the so-called 'metal protein attenuating compound' approach, with the lead molecule PBT2 having successfully completed early phase clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21232050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20164561", "endSection": "title" }, { "offsetInBeginSection": 108, "offsetInEndSection": 448, "text": " A recent Phase IIa double-blind, randomized, placebo-controlled trial found that the 250 mg dose of PBT2 was well-tolerated, significantly lowered cerebrospinal fluid (CSF) levels of amyloid-beta42, and significantly improved executive function on a Neuro-psychological Test Battery (NTB) within 12 weeks of treatment in patients with AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20164561", "endSection": "abstract" }, { "offsetInBeginSection": 1346, "offsetInEndSection": 1415, "text": "These findings further encourage larger-scale testing of PBT2 for AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20164561", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 222, "text": "Recently, CQ and its analog PBT2 have shown encouraging effects in the animal and clinical trials for Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504115", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1092, "text": "Experimental treatments potentially useful for Alzheimer's disease include dimebon, PBT2 and etanercept; the safety and efficacy of the Alzheimer's vaccine remains to be proven, and growth hormone secretagogue and tarenflurbil are likely ineffective. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19742190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "The recent report of positive results from a Phase IIa clinical trial of PBT2, a novel drug that targets amyloid-beta-metal interactions, underscores the value of abnormal transition metal metabolism as a potential therapeutic target in Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953111", "endSection": "abstract" }, { "offsetInBeginSection": 1260, "offsetInEndSection": 1418, "text": "It has performed very satisfactorily in toxicology and Phase I clinical trials and is advancing as a disease-modifying candidate drug for Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18953111", "endSection": "abstract" }, { "offsetInBeginSection": 2631, "offsetInEndSection": 2799, "text": "Future trials that are larger and longer will establish if the effects of PBT2 on biomarkers and cognition that are reported here translate into clinical effectiveness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18672400", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1588, "text": "Small molecules targeting Abeta-metal interactions (e.g., PBT2) are currently advancing through clinical trials and show increasing promise as disease-modifying agents for Alzheimer's disease based on the \"metal hypothesis.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18625454", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1487, "text": "Intracellular translocation of Zn and Cu via the metal chaperone activity of PBT2 may be an important mechanism by which PBT2 improves cognitive function in people with AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21797865", "endSection": "abstract" } ] }, { "body": "What is the basic secondary structure of the variable domains of a typical antibody?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18513436", "http://www.ncbi.nlm.nih.gov/pubmed/9502319", "http://www.ncbi.nlm.nih.gov/pubmed/12566463", "http://www.ncbi.nlm.nih.gov/pubmed/3115977", "http://www.ncbi.nlm.nih.gov/pubmed/8683598", "http://www.ncbi.nlm.nih.gov/pubmed/8589603", "http://www.ncbi.nlm.nih.gov/pubmed/15186484", "http://www.ncbi.nlm.nih.gov/pubmed/3929246", "http://www.ncbi.nlm.nih.gov/pubmed/11297418", "http://www.ncbi.nlm.nih.gov/pubmed/402951" ], "ideal_answer": [ "The variable domains of heavy and light chains of antibodies consist of two \u03b2-sheets. The first one is composed of four strands, A, B, E and D, and the second one is composed of six strands, named A', G, F, C, C' and C''. The antigen binding site is formed by the inter-strand links BC, C\u2032C\u2033 and FG from each domain." ], "concepts": [ "http://www.biosemantics.org/jochem#4000002", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017433", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007136", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042571", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906" ], "type": "summary", "id": "532ad531d6d3ac6a34000013", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 281, "text": "Antibodies are prototypes of multimeric proteins and consist of structurally similar domains. The two variable domains of an antibody (VH and VL) interact through a large hydrophobic interface and can be expressed as covalently linked single-chain Fv (scFv) fragments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9502319", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 1280, "text": "Secondary structure formation, measured by H/D-exchange protection, of a mutant scFv fragment of an antibody after short incubation in 6 M guanidinium chloride was shown to be multiphasic. NMR analysis shows that an intermediate with significant proton protection is observed within the dead time of the manual mixing experiments. Subsequently, the folding reaction proceeds via a biphasic reaction and mass spectrometry analyses of the exchange experiments confirm the existence of two parallel pathways. In the presence of cyclophilin, however, the faster of the two phases vanishes (when followed by intrinsic tryptophan fluorescence), while the slower phase is not significantly enhanced by equimolar cyclophilin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9502319", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1778, "text": "e formation of an early intermediate, which shows amide-proton exchange protection, is independent of proline isomerization. Subsequently, a proline cis-trans isomerization reaction in the rapidly formed intermediate, producing 'non-native' isomers, competes with the fast formation of native species. Interface formation in a folding intermediate of the scFv fragment is proposed to prevent the back-isomerization of these prolines from being efficiently catalyzed by cyclophilin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9502319", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 150, "text": " heavy chain variable domains (VH) lacking their light chain (VL) partner are prime candidates for the design of minimum-size immunoreagents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8589603", "endSection": "abstract" } ] }, { "body": "How does long-range epigenetic silencing (LRES) occur?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "http://www.ncbi.nlm.nih.gov/pubmed/21737484", "http://www.ncbi.nlm.nih.gov/pubmed/20442245", "http://www.ncbi.nlm.nih.gov/pubmed/17099711", "http://www.ncbi.nlm.nih.gov/pubmed/19956686", "http://www.ncbi.nlm.nih.gov/pubmed/22133303", "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "http://www.ncbi.nlm.nih.gov/pubmed/22249255", "http://www.ncbi.nlm.nih.gov/pubmed/20736368", "http://www.ncbi.nlm.nih.gov/pubmed/21098650", "http://www.ncbi.nlm.nih.gov/pubmed/18403637" ], "ideal_answer": [ "Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types.", "Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types. Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer types. LRES can span megabases of DNA and involves broad heterochromatin formation accompanied by hypermethylation of clusters of contiguous CpG islands within the region. It is not clear if LRES is initiated by one critical gene target that spreads and conscripts innocent bystanders, analogous to large genetic deletions or if coordinate silencing of multiple genes is important in carcinogenesis. Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0010495" ], "type": "summary", "id": "57092635cf1c325851000019", "snippets": [ { "offsetInBeginSection": 121, "offsetInEndSection": 296, "text": "Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 900, "text": "We demonstrate that LRES also occurs in murine cancer in vivo and mimics the molecular features of the human phenomenon, namely, downregulation of gene expression, acquisition of inactive histone marks, and DNA hypermethylation of specific CpG islands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract" }, { "offsetInBeginSection": 1517, "offsetInEndSection": 1646, "text": "Malignant regression of cancer cells by in vitro differentiation resulted in partial reversion of LRES and gain of CTCF binding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract" }, { "offsetInBeginSection": 1663, "offsetInEndSection": 1899, "text": "genes in LRES regions are plastically regulated in cell differentiation and hyperproliferation, but are constrained to a coordinated repression by abolishing boundaries and the autonomous regulation of chromatin domains in cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249255", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 897, "text": " Epigenetic gene silencing has always been envisaged as a local event silencing discrete genes, but recent data now indicates that large regions of chromosomes can be co-coordinately suppressed; a process termed long range epigenetic silencing (LRES)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1290, "text": "LRES can span megabases of DNA and involves broad heterochromatin formation accompanied by hypermethylation of clusters of contiguous CpG islands within the region. It is not clear if LRES is initiated by one critical gene target that spreads and conscripts innocent bystanders, analogous to large genetic deletions or if coordinate silencing of multiple genes is important in carcinogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 725, "text": "This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19956686", "endSection": "abstract" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1297, "text": "Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19956686", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 335, "text": "The long-range epigenetic silencing (LRES) can be a frequent occurrence throughout the human genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "title" }, { "offsetInBeginSection": 145, "offsetInEndSection": 336, "text": "By creating an integrated prostate cancer epigenome map using tiling arrays, we show that contiguous regions of gene suppression commonly occur through long-range epigenetic silencing (LRES).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 511, "text": "We identified 47 LRES regions in prostate cancer, typically spanning about 2 Mb and harbouring approximately 12 genes, with a prevalence of tumour suppressor and miRNA genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1187, "text": "We propose that consolidation or effective reduction of the cancer genome commonly occurs in domains through a combination of LRES and LOH or genomic deletion, resulting in reduced transcriptional plasticity within these regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 405, "text": "It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17099711", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 811, "text": "Ikaros hypermethylation occurred in the context of a novel long-range epigenetic silencing (LRES) region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737484", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1249, "text": "Our results not only provide the first evidence that LRES can have functional specific effects in cancer but also identify several deregulated Ikaros targets that may contribute to progression in colorectal adenocarcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737484", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 260, "text": "Previously, we showed that gene suppression commonly occurs across chromosome 2q14.2 in colorectal cancer, through a process of long-range epigenetic silencing (LRES), involving a combination of DNA methylation and repressive histone modifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098650", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 466, "text": "We now investigate whether LRES also occurs in prostate cancer across this 4-Mb region and whether differential DNA methylation of 2q14.2 genes could provide a regional panel of prostate cancer biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098650", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1295, "text": "Consistent with LRES in colorectal cancer, we found regional epigenetic remodeling across 2q14.2 in prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098650", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 771, "text": "We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22133303", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 470, "text": "Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "The CpG island methylator phenotype correlates with long-range epigenetic silencing in colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18403637", "endSection": "title" }, { "offsetInBeginSection": 423, "offsetInEndSection": 899, "text": "We now know that tumour suppressor genes, with CpG island-associated promoters, are commonly hypermethylated and silenced in cancer, but we do not understood what triggers this process or when it occurs during carcinogenesis. Epigenetic gene silencing has always been envisaged as a local event silencing discrete genes, but recent data now indicates that large regions of chromosomes can be co-coordinately suppressed; a process termed long range epigenetic silencing (LRES).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 1064, "text": "Epigenetic gene silencing has always been envisaged as a local event silencing discrete genes, but recent data now indicates that large regions of chromosomes can be co-coordinately suppressed; a process termed long range epigenetic silencing (LRES). LRES can span megabases of DNA and involves broad heterochromatin formation accompanied by hypermethylation of clusters of contiguous CpG islands within the region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "endSection": "abstract" } ] }, { "body": "What is the mode of inheritance of Acromicric dysplasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22791552", "http://www.ncbi.nlm.nih.gov/pubmed/19396027", "http://www.ncbi.nlm.nih.gov/pubmed/11694546" ], "ideal_answer": [ "Acromicric dysplasia has an autosomal dominant mode of inheritance" ], "exact_answer": [ "autosomal dominant" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001848" ], "type": "factoid", "id": "53318685d6d3ac6a3400003d", "snippets": [ { "offsetInBeginSection": 696, "offsetInEndSection": 840, "text": "AD has an autosomal dominant mode of inheritance, distinct facial and skeleton features (a hoarse voice and internal notch of the femoral head).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791552", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 830, "text": "Finally, WMS is transmitted either by an autosomal dominant or an autosomal recessive (AR) mode of inheritance, GD by an autosomal recessive mode of inheritance and AD by an autosomal dominant mode of inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19396027", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1507, "text": "The condition appeared to be sporadic in 16 cases but the observation of vertical transmission in three families was consistent with an autosomal dominant mode of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11694546", "endSection": "abstract" } ] }, { "body": "Can RNAPolII function as an RNA-dependent RNA-polymerase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17855633", "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "http://www.ncbi.nlm.nih.gov/pubmed/18004386", "http://www.ncbi.nlm.nih.gov/pubmed/17132145", "http://www.ncbi.nlm.nih.gov/pubmed/20943989", "http://www.ncbi.nlm.nih.gov/pubmed/15964997", "http://www.ncbi.nlm.nih.gov/pubmed/15827195", "http://www.ncbi.nlm.nih.gov/pubmed/16624367" ], "ideal_answer": [ "RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA template, can extend RNA by several nucleotides in the absence of DNA, and has been implicated in the replication of the RNA genomes of hepatitis delta virus (HDV) and plant viroids. The RdRP activity of Pol II provides a missing link in molecular evolution, because it suggests that Pol II evolved from an ancient replicase that duplicated RNA genomes.", "There is, however, evidence that Pol II also possesses RNA-dependent RNA polymerase (RdRP) activity. Here we show the intrinsic RdRP activity of Pol II with only pure polymerase, an RNA template-product scaffold and nucleoside triphosphates (NTPs). RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity. We conclude that influenza A virus replication requires RNAP-II activity not just to provide capped mRNA substrates but also to facilitate nuclear export of selected viral mRNAs.", "RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA" ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012319" ], "type": "yesno", "id": "571696d9cb4ef8864c000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 913, "text": ". Our studies provide compelling evidence that mammalian Pol II acts as an RdRP to control the stability of a cellular RNA by extending its 3'-end.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 407, "text": "here is, however, evidence that Pol II also possesses RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA template, can extend RNA by several nucleotides in the absence of DNA, and has been implicated in the replication of the RNA genomes of hepatitis delta virus (HDV) and plant viroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18004386", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1341, "text": "The RdRP activity of Pol II provides a missing link in molecular evolution, because it suggests that Pol II evolved from an ancient replicase that duplicated RNA genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18004386", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1017, "text": "The present findings provide a framework for further studies to elucidate the mechanistic principles of transcription by a viral RNA polymerase and have implications for the regulation of Pol II activities in infected cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15827195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Influenza A virus transcribes its segmented negative sense RNA genome in the nuclei of infected cells in a process long known to require host RNA polymerase II (RNAP-II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17132145", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1385, "text": "We conclude that influenza A virus replication requires RNAP-II activity not just to provide capped mRNA substrates but also to facilitate nuclear export of selected viral mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17132145", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 985, "text": "Thus, influenza virus specifically interferes with Pol II elongation, but not Pol II initiation. We propose that influenza virus RNA polymerase, by binding to the CTD of initiating Pol II and subsequent cleavage of the capped 5' end of the nascent transcript, triggers premature Pol II termination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16624367", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 737, "text": "We show that RNA polymerase II (RNAPolII) preinitiation complex recruitment and H3 Lys 4 (H3-K4) methylation at the Xist promoter form the basis of the Xist expression profiles that drives both imprinted and random XCI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15964997", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 1096, "text": "Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17855633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Association of the influenza A virus RNA-dependent RNA polymerase with cellular RNA polymerase II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15827195", "endSection": "title" }, { "offsetInBeginSection": 126, "offsetInEndSection": 290, "text": "It is also well established that viral RNA-dependent RNA polymerase (vRNP) associates with cellular RNA polymerase II (Pol II), on which viral replication depends. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20943989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity. Natural cellular RNA substrates of mammalian Pol II, however, have not been identified and the cellular function of the Pol II RdRP activity is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395899", "endSection": "title" } ] }, { "body": "Which are the best treatment options to treat Helicobacter pylori?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23388847", "http://www.ncbi.nlm.nih.gov/pubmed/23021657", "http://www.ncbi.nlm.nih.gov/pubmed/22322786", "http://www.ncbi.nlm.nih.gov/pubmed/22404517", "http://www.ncbi.nlm.nih.gov/pubmed/20485704", "http://www.ncbi.nlm.nih.gov/pubmed/20429828", "http://www.ncbi.nlm.nih.gov/pubmed/19490560" ], "ideal_answer": [ "The best treatment options for eradication of Helicobacter pylori involve triple or quadruple drugs therapy with different types of antibiotics.\nBismuth may be also an additional option. Proton pump inhibitors are also included in treatment.\nThe more effective drug list includes: amoxicillin, claritromycin, metronidazole rifabutin.\nAlso chitosan microspheres with Eudragit L100 have been tested." ], "exact_answer": [ [ "amoxicillin" ], [ "metronidazole" ], [ "claritromycin" ], [ "Proton pump inhibithors" ], [ "rifabutin" ], [ "Eudragit L100" ] ], "type": "list", "id": "518cb5ab310faafe08000008", "snippets": [ { "offsetInBeginSection": 181, "offsetInEndSection": 332, "text": "Triple therapy, which has been the mainstay of treatment in many countries over the last decade, now has suboptimal results in many parts of the world.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388847", "endSection": "sections.0" }, { "offsetInBeginSection": 620, "offsetInEndSection": 782, "text": "equential therapy and quadruple therapy (either bismuth-based or non-bismuth-based) are the best current options to replace initial treatment with triple therapy.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23388847", "endSection": "sections.0" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1080, "text": "olecular tests can be used to detect H. pylori and clarithromycin and/or fluoroquinolone resistance in gastric biopsies without necessitating culture. In regions of high clarithromycin resistance, such as France, sequential treatment or bismuth-containing quadruple therapies are replacing standard triple therapies for the first-line empirical treatment.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23021657", "endSection": "sections.0" }, { "offsetInBeginSection": 1366, "offsetInEndSection": 1460, "text": "The evidence in favour of bismuth compounds for treating infected children is still not clear.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22404517", "endSection": "sections.0" }, { "offsetInBeginSection": 323, "offsetInEndSection": 457, "text": "Chitosan microspheres with multiple Eudragit L100 cores were easily prepared by a new emulsification/coagulation encapsulating method.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22322786", "endSection": "sections.0" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1026, "text": "the multi-core chitosan microspheres could serve as a satisfactory vehicle for stomach-specific delivery of hydrophilic antibiotics.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22322786", "endSection": "sections.0" }, { "offsetInBeginSection": 499, "offsetInEndSection": 648, "text": "Treatment consisted of a one-week regimen containing a PPI twice daily, amoxicillin (A) 1 g twice daily and rifabutin (R) 300 mg once daily (PPI-AR).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20485704", "endSection": "sections.0" }, { "offsetInBeginSection": 829, "offsetInEndSection": 956, "text": "Pretreatment antibiotic susceptibility to metronidazole, clarithromycin and A was evaluated using a validated epsilometer test.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20485704", "endSection": "sections.0" }, { "offsetInBeginSection": 289, "offsetInEndSection": 564, "text": "four different strategies for prevention of rebleeding in patients with peptic ulcer hemorrhage: 1) test for H. pylori and treatment, if positive; 2) proton pump inhibitor maintenance; 3) no preventive treatment; 4) empirical H. pylori eradication immediately after bleeding.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19490560", "endSection": "sections.0" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1225, "text": "Empirical H. pylori eradication was the dominant strategy: its estimated rate of recurrent bleeding was lower (6.1%) than those of strategies 1 (7.4%), 2 (11.1%), and 3 (18.4%) and it was the least expensive strategy. The results remained stable when variables were changed inside a wide range of plausible values.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19490560", "endSection": "sections.0" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1721, "text": "In patients with bleeding peptic ulcer, empirical treatment of H. pylori infection immediately after feeding is restarted is the most cost-effective strategy for preventing recurrent hemorrhage.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19490560", "endSection": "sections.0" } ] }, { "body": "List sclerostin interaction partners.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22206666", "http://www.ncbi.nlm.nih.gov/pubmed/20951118", "http://www.ncbi.nlm.nih.gov/pubmed/17002572", "http://www.ncbi.nlm.nih.gov/pubmed/15199066" ], "ideal_answer": [ "alkaline phosphatase\ncarbonic anhydrase\ngremlin-1\nfetuin A\nmidkine\nannexin A1 \nannexin A2\ncollagen \u03b11\ncasein kinase II \nsecreted frizzled related protein 4\nPhex\nasporin\nfollistatin\nerbB-3\nLRP5 \nnoggin" ], "exact_answer": [ [ "alkaline phosphatase" ], [ "carbonic anhydrase" ], [ "gremlin-1" ], [ "fetuin A" ], [ "midkine" ], [ "annexin A1" ], [ "annexin A2" ], [ "collagen \u03b11" ], [ "casein kinase II" ], [ "secreted frizzled related protein 4" ], [ "Phex" ], [ "asporin" ], [ "follistatin" ], [ "erbB-3" ], [ "LRP5" ], [ "noggin" ] ], "type": "list", "id": "570a6d03cf1c325851000025", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 1277, "text": " Several previously unidentified full-length sclerostin-interacting proteins such as alkaline phosphatase, carbonic anhydrase, gremlin-1, fetuin A, midkine, annexin A1 and A2, and collagen \u03b11, which have established roles in bone formation or resorption processes, were bound to the sclerostin-MBP amylose resin but not to the MBP amylose resin. Other full-length sclerostin-interacting proteins such as casein kinase II and secreted frizzled related protein 4 that modulate Wnt signaling were identified. Several peptides derived from proteins such as Phex, asporin and follistatin that regulate bone metabolism also bound sclerostin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22206666", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 450, "text": "We identified an interaction between sclerostin and the carboxyl-terminal portion of the receptor tyrosine-protein kinase erbB-3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20951118", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 690, "text": "Sclerostin, SOST, the gene affected in this disease, has been postulated to exert its activity by functioning as a BMP antagonist. However, recent evidence indicates that SOST is highly related to Wise, which can also modulate the Wnt pathway by binding to LRP5 and LRP6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17002572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17002572", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 300, "text": "We show that recombinant sclerostin and noggin bound to each other with high affinity (K(D) = 2.92 nm).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15199066", "endSection": "abstract" } ] }, { "body": "Under which conditions does AMPK phosphorylate TSC2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15261145", "http://www.ncbi.nlm.nih.gov/pubmed/19245654", "http://www.ncbi.nlm.nih.gov/pubmed/14651849", "http://www.ncbi.nlm.nih.gov/pubmed/24173372", "http://www.ncbi.nlm.nih.gov/pubmed/18439900", "http://www.ncbi.nlm.nih.gov/pubmed/16483933", "http://www.ncbi.nlm.nih.gov/pubmed/17041622" ], "ideal_answer": [ "The AMP-activated serine/threonine protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes, and it is activated under conditions of low intracellular ATP following stresses such as nutrient deprivation or hypoxia.", "The AMP-activated serine/threonine protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes that is activated under conditions of low intracellular ATP following stresses such as nutrient deprivation or hypoxia." ], "type": "summary", "id": "56cd765b5795f9a73e000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "The AMP-activated serine/threonine protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes that is activated under conditions of low intracellular ATP following stresses such as nutrient deprivation or hypoxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19245654", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1155, "text": "AMPK directly phosphorylates at least two proteins to induce rapid suppression of mTORC1 activity, the TSC2 tumour suppressor and the critical mTORC1 binding subunit raptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19245654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18439900", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 511, "text": "TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway. Under energy starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates TSC2 and enhances its activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14651849", "endSection": "abstract" }, { "offsetInBeginSection": 1811, "offsetInEndSection": 2113, "text": "Conversely, energy depletion reduces Rheb-GTP charging through the ability of the adenosine monophosphate-activated protein kinase to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function, as well as by HIFalpha-mediated transcriptional responses that act upstream of the TSC1/2 complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17041622", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 630, "text": "Under energy starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates TSC2 and enhances its activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14651849", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 925, "text": "Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15261145", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 569, "text": "Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16483933", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 592, "text": "AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1; however, TSC2-deficient cells remain responsive to energy stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18439900", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 512, "text": "Under energy starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates TSC2 and enhances its activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14651849", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 442, "text": "AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1; however, TSC2-deficient cells remain responsive to energy stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18439900", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 640, "text": "Under energy starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates TSC2 and enhances its activity. Phosphorylation of TSC2 by AMPK is required for translation regulation and cell size control in response to energy deprivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14651849", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 512, "text": "Here, we describe that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway. Under energy starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates TSC2 and enhances its activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14651849", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 403, "text": "Once activated under the various metabolic stress conditions, AMPK regulates a multitude of metabolic pathways to balance cellular energy. In addition, AMPK also induces cell cycle arrest or apoptosis through several tumor suppressors including LKB1, TSC2, and p53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24173372", "endSection": "abstract" } ] }, { "body": "What imaging modalities have been listed as method of choice to diagnose CSF leak?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11109603", "http://www.ncbi.nlm.nih.gov/pubmed/19242563", "http://www.ncbi.nlm.nih.gov/pubmed/19723768", "http://www.ncbi.nlm.nih.gov/pubmed/11331153", "http://www.ncbi.nlm.nih.gov/pubmed/8519147" ], "ideal_answer": [ "CT cisternography in the investigation of cerebrospinal fluid rhinorrhoea. CTC is an accurate, well-tolerated procedure and should be regarded as the method of choice for investigation of this condition.\n...unenhanced (three-dimensional constructive interference in steady state (3D-CISS)...In conclusion, 3D-CISS is a non-invasive and reliable technique, and should be the first-choice method to localise CSF leak." ], "exact_answer": [ [ "CT cisternography", "CTC" ], [ "three-dimensional constructive interference in steady state", "3D-CISS" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002555", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015170", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003952", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002558", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002559", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001826", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059906", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008919" ], "type": "list", "id": "5326300fd6d3ac6a34000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "CT cisternography in the investigation of cerebrospinal fluid rhinorrhoea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8519147", "endSection": "title" }, { "offsetInBeginSection": 775, "offsetInEndSection": 903, "text": "CTC is an accurate, well-tolerated procedure and should be regarded as the method of choice for investigation of this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8519147", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 204, "text": "Currently the method of choice for cerebrospinal fluid detection is qualitative determination of beta-2-transferrin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11109603", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 527, "text": "surgery the use of intrathecal sodium-fluorescein improves visualisation of the site of leakage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11109603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The contribution of 3D-CISS and contrast-enhanced MR cisternography in detecting cerebrospinal fluid leak in patients with rhinorrhoea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19723768", "endSection": "title" }, { "offsetInBeginSection": 1265, "offsetInEndSection": 1390, "text": " In conclusion, 3D-CISS is a non-invasive and reliable technique, and should be the first-choice method to localise CSF leak.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19723768", "endSection": "abstract" }, { "offsetInBeginSection": 63, "offsetInEndSection": 287, "text": "unenhanced (three-dimensional constructive interference in steady state (3D-CISS)) and contrast-enhanced MR cisternography (CE-MRC) in detecting the localisation of cerebrospinal fluid (CSF) leak in patients with rhinorrhoea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19723768", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 461, "text": "The diagnostic work-up included lumbar tapping and measurement of CSF opening pressure, radioisotope cisternography, brain and spinal magnetic resonance imaging (MRI), and computed tomography (CT) myelography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19242563", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 362, "text": "A Tc-99m diethyltriaminepentacetic acid radionuclide cisternography (RNC) showed the accumulation of radioactivity in the area of the subarachnoid space, the poor migration of the isotope over the convexities, and the early appearance of kidney and bladder activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11331153", "endSection": "abstract" } ] }, { "body": "Which are currently available software tools for detecting rare codon clusters in coding sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18923675", "http://www.ncbi.nlm.nih.gov/pubmed/18457591", "http://www.ncbi.nlm.nih.gov/pubmed/22467916", "http://www.ncbi.nlm.nih.gov/pubmed/10689191", "http://www.ncbi.nlm.nih.gov/pubmed/22199385", "http://www.ncbi.nlm.nih.gov/pubmed/20167116" ], "ideal_answer": [ "Rare codon clusters (RCCs) correspond to regions along mRNA sequences where among the possible choices of synonymous codons those with lower usage are observed. Due to the fact that relative codon frequencies have been shown to correlate with their cognate tRNA frequencies, RCCs indicate possible translational attenuation sites. A few tools specific for this task have been described in the literature, namely: LaTcOm, %MinMax, PAUSE, Sherlocc, Sliding Window (RiboTempo)" ], "exact_answer": [ [ "LaTcOm" ], [ "%MinMax" ], [ "PAUSE" ], [ "Sherlocc" ], [ "Sliding Window", "RiboTempo" ] ], "type": "list", "id": "51be411b047fa84d1d000006", "snippets": [ { "offsetInBeginSection": 631, "offsetInEndSection": 755, "text": "Our program Sherlocc, detects statistically relevant conserved rare codon clusters and produces a user-friendly HTML output.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22467916", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "LaTcOm: a web server for visualizing rare codon clusters in coding sequences", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22199385", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 133, "text": "We present LaTcOm, a new web tool, which offers several alternative methods for 'rare codon cluster' (RCC) identification", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22199385", "endSection": "sections.0" }, { "offsetInBeginSection": 209, "offsetInEndSection": 485, "text": "three RCC detection schemes are implemented: the recently described %MinMax algorithm and a simplified sliding window approach, along with a novel modification of a linear-time algorithm for the detection of maximally scoring subsequences tailored to the RCC detection problem", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22199385", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "The PAUSE software has been developed as a new tool to study translational control over protein targeting. This makes it possible to correlate the position of clusters of rare codons in a gene, predicted to cause a translational pause, with the position of hydrophobic stretches in the encoded protein, predicted to span a membrane or to act as a cleavable signal for targeting to the secretory pathway.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10689191", "endSection": "sections.0" } ] }, { "body": "How many tissue kallikrein genes are present in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15015574", "http://www.ncbi.nlm.nih.gov/pubmed/20180637", "http://www.ncbi.nlm.nih.gov/pubmed/16800725", "http://www.ncbi.nlm.nih.gov/pubmed/11006094", "http://www.ncbi.nlm.nih.gov/pubmed/21072173", "http://www.ncbi.nlm.nih.gov/pubmed/12725528", "http://www.ncbi.nlm.nih.gov/pubmed/12439719", "http://www.ncbi.nlm.nih.gov/pubmed/17275179", "http://www.ncbi.nlm.nih.gov/pubmed/23093268", "http://www.ncbi.nlm.nih.gov/pubmed/15516960", "http://www.ncbi.nlm.nih.gov/pubmed/18627305", "http://www.ncbi.nlm.nih.gov/pubmed/14710225", "http://www.ncbi.nlm.nih.gov/pubmed/16829021", "http://www.ncbi.nlm.nih.gov/pubmed/20354523", "http://www.ncbi.nlm.nih.gov/pubmed/20103546", "http://www.ncbi.nlm.nih.gov/pubmed/21741862", "http://www.ncbi.nlm.nih.gov/pubmed/17210241", "http://www.ncbi.nlm.nih.gov/pubmed/21596022", "http://www.ncbi.nlm.nih.gov/pubmed/11522960", "http://www.ncbi.nlm.nih.gov/pubmed/15192120", "http://www.ncbi.nlm.nih.gov/pubmed/10662548", "http://www.ncbi.nlm.nih.gov/pubmed/11177570", "http://www.ncbi.nlm.nih.gov/pubmed/16800742", "http://www.ncbi.nlm.nih.gov/pubmed/1697365", "http://www.ncbi.nlm.nih.gov/pubmed/15588589", "http://www.ncbi.nlm.nih.gov/pubmed/20574445", "http://www.ncbi.nlm.nih.gov/pubmed/16170411", "http://www.ncbi.nlm.nih.gov/pubmed/12439720", "http://www.ncbi.nlm.nih.gov/pubmed/11258672", "http://www.ncbi.nlm.nih.gov/pubmed/16800744", "http://www.ncbi.nlm.nih.gov/pubmed/12925213", "http://www.ncbi.nlm.nih.gov/pubmed/12727843", "http://www.ncbi.nlm.nih.gov/pubmed/11478802" ], "ideal_answer": [ "Tissue kallikreins (KLKs) are a group of closely related serine proteinases that are represented by multigene families in the human genome. The human tissue kallikrein gene family consists of 15 genes, denoted KLK1\u2013KLK15, tandemly arranged on chromosomal locus 19q13.4." ], "exact_answer": [ "15" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007610", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020840" ], "type": "factoid", "id": "511a3573df1ebcce7d000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Tissue kallikreins are a group of closely related serine proteinases that are represented by multigene families in mice and rats.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1697365", "endSection": "sections.0" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1221, "text": "Our map specifies the distance between genes to one base pair accuracy, the relative location, and the direction of transcription of all 15 genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11006094", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The human tissue Kallikrein family consists of 15 genes with the majority shown to be differentially expressed in cancers and/or indicators of cancer prognosis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21741862", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and putative proteolytic functions.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20103546", "endSection": "sections.0" }, { "offsetInBeginSection": 205, "offsetInEndSection": 382, "text": "The 15 human and 24 mouse kallikreins have been implicated in pathophysiology of brain, kidney, and respiratory and reproductive systems and often are used as cancer biomarkers.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17210241", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Kallikrein gene families have been identified previously in genomes of the human, the mouse, and the rat, and individual kallikrein-like genes have been found in many more species.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16829021", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "The human tissue kallikrein family of serine proteases (hK1-hK15 encoded by the genes KLK1-KLK15) is involved in several cancer-related processes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16800744", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The tissue kallikrein gene family consists of 15 genes tandemly arranged on human chromosome 19q13.4.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16800742", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Human kallikreins are a cluster of 15 serine protease genes located in the chromosomal band 19q13.4, a non-randomly rearranged region in many solid tumors, including pancreatic cancer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15015574", "endSection": "sections.0" }, { "offsetInBeginSection": 102, "offsetInEndSection": 224, "text": "Tissue kallikrein genes (KLKs) are found on chromosome 19q13.3-4 as a gene cluster encoding 15 different serine proteases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12925213", "endSection": "sections.0" }, { "offsetInBeginSection": 305, "offsetInEndSection": 450, "text": "Project to perform in silico analyses of the expression pattern of the 15 human KLK genes in normal and cancerous ovarian tissues and cell lines.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12727843", "endSection": "sections.0" }, { "offsetInBeginSection": 85, "offsetInEndSection": 250, "text": "Novel kallikrein genes were cloned recently, and it was shown that the human kallikrein family contains 15 genes tandemly aligned on chromosomal locus 19q13.3-q13.4.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12725528", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "The human kallikrein gene family consists of 15 serine proteases.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11522960", "endSection": "sections.0" }, { "offsetInBeginSection": 434, "offsetInEndSection": 555, "text": "We have recently characterized the human kallikrein gene locus on chromosome 19q13.4, which includes 15 kallikrein genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11478802", "endSection": "sections.0" }, { "offsetInBeginSection": 293, "offsetInEndSection": 531, "text": "The human tissue kallikrein and kallikrein-related peptidases (KLKs), encoded by the largest contiguous cluster of protease genes in the human genome, are secreted serine proteases with diverse expression patterns and physiological roles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23093268", "endSection": "sections.0" }, { "offsetInBeginSection": 106, "offsetInEndSection": 186, "text": "that forms the largest cluster of contiguous protease genes in the human genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21596022", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases encoded by the largest uninterrupted cluster of protease-encoding genes within the human genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20180637", "endSection": "sections.0" }, { "offsetInBeginSection": 779, "offsetInEndSection": 899, "text": "In this review, we describe the organization of the kallikrein locus and the structure of kallikrein genes and proteins.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20103546", "endSection": "sections.0" }, { "offsetInBeginSection": 190, "offsetInEndSection": 317, "text": "The human tissue kallikrein gene family is the largest contiguous family of proteases in the human genome, containing 15 genes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18627305", "endSection": "sections.0" }, { "offsetInBeginSection": 246, "offsetInEndSection": 352, "text": "Human tissue kallikrein genes represent the largest contiguous group of proteases within the human genome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17275179", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Human tissue kallikreins (hKs), which are encoded by the largest contiguous cluster of protease genes in the human genome, are secreted serine proteases with diverse expression patterns and physiological roles.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15516960", "endSection": "sections.0" } ] }, { "body": "Does the Oncotype DX test work with paraffin embedded tissues?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18922117", "http://www.ncbi.nlm.nih.gov/pubmed/17463177", "http://www.ncbi.nlm.nih.gov/pubmed/23074401", "http://www.ncbi.nlm.nih.gov/pubmed/17140367", "http://www.ncbi.nlm.nih.gov/pubmed/16361546", "http://www.ncbi.nlm.nih.gov/pubmed/17039265" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7572812", "o": "Paraffin" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0030415", "o": "http://linkedlifedata.com/resource/umls/label/A9424108" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17999423", "o": "Paraffin" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8438050", "o": "PARAFFIN" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A16755941", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ], "ideal_answer": [ "Yes, the Oncotype DX test works with paraffin embedded tissue." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016612" ], "type": "yesno", "id": "514a0f0ad24251bc05000052", "snippets": [ { "offsetInBeginSection": 2732, "offsetInEndSection": 3135, "text": "The Oncotype-DX Breast Cancer Assay (Genomic Health, Redwood City, CA) quantifies gene expression for 21 genes in breast cancer tissue by performing reverse transcription polymerase chain reaction (RT-PCR) on formalin-fixed paraffin-embedded (FFPE) tumour blocks that are obtained during initial surgery (lumpectomy, mastectomy, or core biopsy) of women with early breast cancer that is newly diagnosed.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074401", "endSection": "sections.0" }, { "offsetInBeginSection": 211, "offsetInEndSection": 546, "text": "Oncotype DXtrade mark, is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue, which allows physicians to predict subgroups of hormone-receptor-positive, node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18922117", "endSection": "sections.0" }, { "offsetInBeginSection": 12, "offsetInEndSection": 250, "text": "Oncotype DX is a clinically validated, high-complexity, multianalyte reverse transcription-PCR genomic test that predicts the likelihood of breast cancer recurrence in early-stage, node-negative, estrogen receptor-positive breast cancer. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17463177", "endSection": "sections.0" }, { "offsetInBeginSection": 512, "offsetInEndSection": 578, "text": "We therefore investigated the analytical performance of the assay.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17463177", "endSection": "sections.0" }, { "offsetInBeginSection": 588, "offsetInEndSection": 848, "text": "Assays used a pooled RNA sample from fixed paraffin-embedded tissues to evaluate the analytical performance of a 21-gene panel with respect to amplification efficiency, precision, linearity, and dynamic range, as well as limits of detection and quantification.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17463177", "endSection": "sections.0" }, { "offsetInBeginSection": 726, "offsetInEndSection": 960, "text": "One such strategy is the 21-gene assay (Oncotype DX), which is currently in commercial use in the USA. One advantage of this test is the use of paraffin-embedded blocks instead of previous methods, which required fresh frozen tissue. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17140367", "endSection": "sections.0" }, { "offsetInBeginSection": 119, "offsetInEndSection": 263, "text": "We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. ", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17039265", "endSection": "sections.0" }, { "offsetInBeginSection": 590, "offsetInEndSection": 700, "text": "In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17039265", "endSection": "sections.0" }, { "offsetInBeginSection": 377, "offsetInEndSection": 415, "text": "RNA was extracted from paraffin blocks", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16361546", "endSection": "sections.0" }, { "offsetInBeginSection": 55, "offsetInEndSection": 114, "text": "to develop the 21-gene Recurrence Score assay (Oncotype DX)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16361546", "endSection": "sections.0" } ] }, { "body": "Where does CTCF colocalize with cohesin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23150255", "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "http://www.ncbi.nlm.nih.gov/pubmed/18219272", "http://www.ncbi.nlm.nih.gov/pubmed/21606361", "http://www.ncbi.nlm.nih.gov/pubmed/20159591", "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "http://www.ncbi.nlm.nih.gov/pubmed/21550623" ], "ideal_answer": [ "Cohesin subunits associate with viral and cellular CTCF sites involved in complex gene regulation and chromatin organization. Cohesin cobinds across the genome with transcription factors independently of CTCF, plays a functional role in estrogen-regulated transcription, and may help to mediate tissue-specific transcriptional responses via long-range chromosomal interactions.\nNumerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement. Cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci." ], "exact_answer": [ "In imprinted and repressed, highly compacted loci that are prone to recombination events." ], "concepts": [ "http://www.uniprot.org/uniprot/CTCF_HUMAN", "http://www.uniprot.org/uniprot/CTCF_RAT", "http://amigo.geneontology.org/amigo/term/GO:0008278" ], "type": "factoid", "id": "56c5c7915795f9a73e000004", "snippets": [ { "offsetInBeginSection": 773, "offsetInEndSection": 958, "text": "In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150255", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 560, "text": "To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 887, "text": " In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1402, "text": "Finally, we observe that the presence of mirrored CTCF binding events at promoters and their nearby cohesin-bound enhancers is associated with elevated expression levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 305, "text": "Recently, cohesins have been implicated in transcriptional regulation and insulation through genome-wide colocalization with the insulator protein CTCF, including involvement at the imprinted H19/Igf2 locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 542, "text": "Here we report that cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 871, "text": " To determine the functional importance of the binding of CTCF and cohesins at the three imprinted loci, CTCF and cohesins were depleted in mouse embryonic fibroblast cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "endSection": "abstract" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1283, "text": "Results of these experiments demonstrate an unappreciated role for CTCF and cohesins in the repression of imprinted genes in somatic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 383, "text": "Here, we show in different cell types that cohesin functionally behaves as a tissue-specific transcriptional regulator, independent of CTCF binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 596, "text": "By performing matched genome-wide binding assays (ChIP-seq) in human breast cancer cells (MCF-7), we discovered thousands of genomic sites that share cohesin and estrogen receptor alpha (ER) yet lack CTCF binding", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 834, "text": "By use of human hepatocellular carcinoma cells (HepG2), we found that liver-specific transcription factors colocalize with cohesin independently of CTCF at liver-specific targets that are distinct from those found in breast cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1526, "text": "Together, our data show that cohesin cobinds across the genome with transcription factors independently of CTCF, plays a functional role in estrogen-regulated transcription, and may help to mediate tissue-specific transcriptional responses via long-range chromosomal interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 1004, "text": " Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 789, "text": "These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606361", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1532, "text": "We conclude that cohesins interact with CTCF in mid-S phase and repress CTCF-regulated genes in a cell cycle-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "endSection": "abstract" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1788, "text": "We propose that the CTCF-cohesin complex plays a critical role in regulating the cell cycle control of viral gene expression during latency and that failure to maintain cell cycle control of latent transcripts inhibits host cell proliferation and survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1202, "text": "We conclude that cohesin subunits associate with viral and cellular CTCF sites involved in complex gene regulation and chromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18219272", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1068, "text": "Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1139, "text": "In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23150255", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 705, "text": "Here, we show that ATRX, MeCP2, and cohesin, chromatin regulators implicated in ATR-X, RTT, and CdLS syndromes, respectively, interact in the brain and colocalize at the H19 imprinting control region (ICR) with preferential binding on the maternal allele.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20159591", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1173, "text": "Subcellular distribution of CTCF and colocalization with cohesins also varied across the cell cycle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 626, "text": "ChIP sequencing was performed on pro-B cells, revealing colocalization of CTCF and Rad21 binding at ~60 sites throughout the V(H) region and 2 other sites within the Igh locus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21606361", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 306, "text": "Recently, cohesins have been implicated in transcriptional regulation and insulation through genome-wide colocalization with the insulator protein CTCF, including involvement at the imprinted H19/Igf2 locus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 426, "text": "CTCF colocalizes with cohesin but not RNA Polymerase II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21550623", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 881, "text": "Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 1010, "text": "Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 499, "text": "Here we report that cohesins colocalize with CTCF at two additional imprinted loci,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "endSection": "abstract" } ] }, { "body": "Name triad of Wernicke encephalopathy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21121997", "http://www.ncbi.nlm.nih.gov/pubmed/10328278", "http://www.ncbi.nlm.nih.gov/pubmed/24099834", "http://www.ncbi.nlm.nih.gov/pubmed/25550705", "http://www.ncbi.nlm.nih.gov/pubmed/3469966", "http://www.ncbi.nlm.nih.gov/pubmed/9417174", "http://www.ncbi.nlm.nih.gov/pubmed/21519777", "http://www.ncbi.nlm.nih.gov/pubmed/17595443", "http://www.ncbi.nlm.nih.gov/pubmed/19571457", "http://www.ncbi.nlm.nih.gov/pubmed/14644703", "http://www.ncbi.nlm.nih.gov/pubmed/22332852", "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "http://www.ncbi.nlm.nih.gov/pubmed/23935638", "http://www.ncbi.nlm.nih.gov/pubmed/24620429", "http://www.ncbi.nlm.nih.gov/pubmed/24379094", "http://www.ncbi.nlm.nih.gov/pubmed/7424767" ], "ideal_answer": [ "Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency." ], "exact_answer": [ [ "ophthalmoplegia" ], [ "ataxia" ], [ "confusion" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014899", "http://www.disease-ontology.org/api/metadata/DOID:2384" ], "type": "list", "id": "56be143eef6e394741000009", "snippets": [ { "offsetInBeginSection": 150, "offsetInEndSection": 324, "text": "In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25550705", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1023, "text": "The classic triad consists of encephalopathy, oculomotor dysfunction and gait ataxia but is not seen in a majority of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25515801", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 442, "text": "After frequent vomiting, he presented with mental status changes, ocular abnormalities, and truncal ataxia (the classic triad).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24620429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24099834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Wernicke encephalopathy is caused by thiamine deficiency in the central nervous system, and is defined by the triad of confusional symptoms, ocular alterations and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571457", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 447, "text": "The classical triad of clinical symptoms described by Wernicke (gait ataxia, ophthalmoplegia, and confusion) are found in only a third of patients upon initial examination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14644703", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 484, "text": "It was found that only 0.4% of the population studied had the classical triad of Wernicke's encephalopathy, namely confusion, ophthalmoplegia, and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3469966", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 617, "text": "The triad of Wernicke's encephalopathy--global confusional state, ophthalmoplegia and nystagmus, and ataxia--is occasionally seen in chronic alcoholics and is often attenuated by immediate thiamine treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7424767", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1303, "text": "Only six presented with the Wernicke's encephalopathy clinical triad (mental status changes, ocular signs, and ataxia) at neurologic onset; nine eventually demonstrated this triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10328278", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 277, "text": "Wernicke's encephalopathy is a well-described syndrome characterized by the classic triad of confusion, ataxia, and ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23935638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24099834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Wernicke encephalopathy (WE) is an acute neurologic disorder characterized by a triad of ophthalmoplegia, ataxia, and mental confusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9417174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Wernicke's encephalopathy is a metabolic disorder caused by deficiency of thiamine (vitamin B1) seen in alcoholics and even in nonalcoholic patients, classically presenting with a triad of ataxia, ophthalmoplegia, and altered mental status", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21121997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Wernicke's encephalopathy is an acute neurological syndrome due to thiamine deficiency, which is characterized by a typical triad of mental status changes, oculomotor dysfunction and ataxia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21519777", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 425, "text": "The triad of Wernicke's encephalopathy--global confusional state, ophthalmoplegia and nystagmus, and ataxia--is occasionally seen in chronic alcoholics and is often attenuated by immediate thiamine treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7424767", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 300, "text": "In 25/73 (35%) of the patients the classic triad of Wernicke's encephalopathy with ocular symptoms, ataxia and confusion, was found", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332852", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 345, "text": "It was found that only 0.4% of the population studied had the classical triad of Wernicke's encephalopathy, namely confusion, ophthalmoplegia, and ataxia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3469966", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 589, "text": "Wernicke's encephalopathy (WE) is a serious, potentially fatal, neurologic disorder caused by thiamine deficiency (vitamin B(1)), classically described as presenting with a triad of ocular abnormalities, ataxia, and confusion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17595443", "endSection": "abstract" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1309, "text": "Only six presented with the Wernicke's encephalopathy clinical triad (mental status changes, ocular signs, and ataxia) at neurologic onset; nine eventually demonstrated this triad. The high rate of patients diagnosed only at postmortem examination (41.9%) confirms that Wernicke's encephalopathy is underdiagnosed in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10328278", "endSection": "abstract" } ] }, { "body": "Is the PTPN22 gene a biomarker for Rheumatoid Arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21542789", "http://www.ncbi.nlm.nih.gov/pubmed/19445664", "http://www.ncbi.nlm.nih.gov/pubmed/20498205", "http://www.ncbi.nlm.nih.gov/pubmed/21752868", "http://www.ncbi.nlm.nih.gov/pubmed/16309943", "http://www.ncbi.nlm.nih.gov/pubmed/19034456", "http://www.ncbi.nlm.nih.gov/pubmed/20604892", "http://www.ncbi.nlm.nih.gov/pubmed/21607711", "http://www.ncbi.nlm.nih.gov/pubmed/16380915", "http://www.ncbi.nlm.nih.gov/pubmed/18240242", "http://www.ncbi.nlm.nih.gov/pubmed/20398001", "http://www.ncbi.nlm.nih.gov/pubmed/15883854", "http://www.ncbi.nlm.nih.gov/pubmed/20032229", "http://www.ncbi.nlm.nih.gov/pubmed/19404967", "http://www.ncbi.nlm.nih.gov/pubmed/19856886", "http://www.ncbi.nlm.nih.gov/pubmed/20707220", "http://www.ncbi.nlm.nih.gov/pubmed/19950324", "http://www.ncbi.nlm.nih.gov/pubmed/18305142", "http://www.ncbi.nlm.nih.gov/pubmed/16320352", "http://www.ncbi.nlm.nih.gov/pubmed/19648126", "http://www.ncbi.nlm.nih.gov/pubmed/20061955", "http://www.ncbi.nlm.nih.gov/pubmed/19324521", "http://www.ncbi.nlm.nih.gov/pubmed/23242182", "http://www.ncbi.nlm.nih.gov/pubmed/19365265", "http://www.ncbi.nlm.nih.gov/pubmed/18535030", "http://www.ncbi.nlm.nih.gov/pubmed/18812394", "http://www.ncbi.nlm.nih.gov/pubmed/21545847", "http://www.ncbi.nlm.nih.gov/pubmed/21614018", "http://www.ncbi.nlm.nih.gov/pubmed/18398946", "http://www.ncbi.nlm.nih.gov/pubmed/17341507", "http://www.ncbi.nlm.nih.gov/pubmed/21784728", "http://www.ncbi.nlm.nih.gov/pubmed/20560812", "http://www.ncbi.nlm.nih.gov/pubmed/22661644", "http://www.ncbi.nlm.nih.gov/pubmed/18156150", "http://www.ncbi.nlm.nih.gov/pubmed/17666451", "http://www.ncbi.nlm.nih.gov/pubmed/16257177", "http://www.ncbi.nlm.nih.gov/pubmed/20921970", "http://www.ncbi.nlm.nih.gov/pubmed/18648537", "http://www.ncbi.nlm.nih.gov/pubmed/21360494", "http://www.ncbi.nlm.nih.gov/pubmed/20353580", "http://www.ncbi.nlm.nih.gov/pubmed/22427951", "http://www.ncbi.nlm.nih.gov/pubmed/18462498", "http://www.ncbi.nlm.nih.gov/pubmed/20017985" ], "triples": [ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3793", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/PTPN22" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/PTPN22", "o": "PTPN22" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3793", "o": "Rheumatoid arthritis, susceptibility to, 180300" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/PTPN22", "o": "http://www.dbpedia.org/resource/PTPN22" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/999", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/PTPN22" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/999", "o": "http://www4.wiwiss.fu-berlin.de/sider/resource/side_effects/C0003873" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/condition/11608", "o": "Condition #11608 (Rheumatoid Arthritis)" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/999", "o": "Rheumatoid_arthritis" }, { "p": "http://data.linkedct.org/resource/linkedct/condition_name", "s": "http://data.linkedct.org/resource/condition/11608", "o": "Rheumatoid Arthritis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://data.linkedct.org/resource/condition/11608", "o": "http://dbpedia.org/resource/Rheumatoid_arthritis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://data.linkedct.org/resource/condition/11608", "o": "http://yago.org/resource/Rheumatoid_arthritis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/999", "o": "http://www.dbpedia.org/resource/Rheumatoid_arthritis" } ], "ideal_answer": [ "Most association studies have indeed confirmed an association between mutations at the PTPN22 gene and rheumatoid arthritis", "The PTPN22 gene has been repeatedly associated with RA-susceptibility in populations of European ancestry." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001171", "http://www.uniprot.org/uniprot/PTN22_HUMAN", "http://www.uniprot.org/uniprot/PTN22_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:1586", "http://www.uniprot.org/uniprot/SAST_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005258", "http://www.disease-ontology.org/api/metadata/DOID:11042", "http://www.uniprot.org/uniprot/SERPH_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:676", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415" ], "type": "yesno", "id": "52e7870a98d023950500001a", "snippets": [ { "offsetInBeginSection": 1166, "offsetInEndSection": 1413, "text": "Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242182", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1320, "text": "A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti-CCP negative RA, after correction for multiple testing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661644", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 353, "text": "A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427951", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 353, "text": "TPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427951", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 702, "text": "In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427951", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1428, "text": "Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427951", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1235, "text": "the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22427951", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1506, "text": "Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21784728", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1744, "text": "This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21784728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752868", "endSection": "title" }, { "offsetInBeginSection": 876, "offsetInEndSection": 990, "text": " PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR)\u2009=\u20092.21, 95% CI 1.4, 3.4, P\u2009<\u20090.0001]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752868", "endSection": "abstract" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1262, "text": "Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR\u2009=\u20090.44, 95% CI 0.3, 0.7, P\u2009=\u20090.001) and early bone erosion (OR\u2009=\u20090.56, 95% CI 0.4-0.8, P\u2009=\u20090.003), respectively, and independently of HLADR and PTPN22 status", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21752868", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 817, "text": " RA patients (n=333) and controls (n=490) from the Cree/Ojibway NAN population in Central Canada were HLA-DRB1 typed and tested for 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21614018", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 817, "text": "21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21614018", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 343, "text": "Several other genes, including PTPN22 and PADI4, show modest association with RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21607711", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 345, "text": "he HLA locus, particularly HLA-DRB1, is its strongest genetic risk determinant across ethnicities. Several other genes, including PTPN22 and PADI4, show modest association with RA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21607711", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1089, "text": "Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21545847", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 1091, "text": "Several alleles in the epitope-recognition part of the HLA molecule that show the highest association with RA susceptibility, also share a common string of amminoacid residues (the so-called shared-epitope hypothesis). Other variants in potentially pathogenic genes located in non-MHC regions have been implicated by recently performed genome wide analysis studies. These genes include PTPN22, TRAF1-C5, PADI4, STAT4. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21545847", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 627, "text": "Among these genes, PTPN22 plays an outstanding role. CD40, STAT4, PRM1, and TNFAIP3 also seem to be of relevance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542789", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 566, "text": "n particular, genome-wide association studies (GWAS) have provided supportive evidence that RA is a disease with a strong genetic background. Interestingly, a series of candidate genes have been identified outside of the classical major histocompatibility (MHC) locus, which had long been regarded as the major contributor to the pathogenesis of this disease. Among these genes, PTPN22 plays an outstanding role.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21542789", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 504, "text": "HLA-DRB1 and the R620W single-nucleotide polymorphism of PTPN22 were genotyped", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21360494", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1065, "text": "In addition, evidence of a significant interaction between the shared epitope and the risk allele of PTPN22 was observed only in these patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21360494", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1109, "text": "Although SNPs in PADI4 had similar allele frequency among three groups [maximal difference 11%; (P >0.05)], the other three loci revealed statistically significant allele frequency differences (maximal difference 39% (P <0.00001), 13% (P <0.00001), and 8% (P <0.00001) in SLC22A4, PDCD1, and PTPN22, respectively)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15883854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 467, "text": "Several multiple, large-scale, genetic studies on autoimmune-disease-associated SNPs have been reported recently: peptidylarginine deiminase type 4 (PADI4) in rheumatoid arthritis (RA); solute carrier family 22 members 4 and 5 (SLC22A4 and 5) in RA and Crohn's disease (CD); programmed cell death 1 (PDCD1) in systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), and RA; and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in T1D, RA, and SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15883854", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 992, "text": " Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22, CTLA-4 and MIF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16257177", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 975, "text": "Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16257177", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 162, "text": "challenges in identifying genetic polymorphisms that influence the susceptibility to rheumatoid arthritis are the same as those faced in most complex diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16257177", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1085, "text": "Association studies support a role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16309943", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 1086, "text": "Although HLA-DRB1 is the main RA gene, it accounts for only part of the familial risk for RA. HLA-DRB1 alleles are neither necessary nor sufficient to cause the development of RA in a given individual. Several genome scans conducted in populations from France, Japan, North America and UK have confirmed the role of the HLA region and suggested several other susceptibility loci. Association studies support a role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16309943", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 415, "text": "Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16320352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16380915", "endSection": "title" }, { "offsetInBeginSection": 802, "offsetInEndSection": 989, "text": "We found strong evidence of an association of PTPN22 with the development of anti-citrulline antibody-positive RA (odds ratio [OR] 1.49; P=.00002), using previously untested EIRA samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16380915", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1516, "text": " Exploration of our data set with clinically relevant subsets of RA reveals that PTPN22 is associated with an earlier age at disease onset (P=.004) and that PTPN22 has a stronger effect in males than in females (P=.03)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16380915", "endSection": "abstract" }, { "offsetInBeginSection": 1711, "offsetInEndSection": 1960, "text": " Given the strong statistical power to replicate a true-positive association in this study, our results provide support for PTPN22, CTLA4, and PADI4 as RA susceptibility genes and demonstrate novel associations with clinically relevant subsets of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16380915", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1329, "text": "In logistic regression analysis, ACPA predicted RA-development independent of PTPN22, while the PTPN22 polymorphism had no independent effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341507", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1653, "text": "In this Dutch cohort of UA-patients, the PTPN22 1858T allele does not markedly improve individual decision-making to predict RA-development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Risk of progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele in anti-citrullinated peptide antibody positive patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341507", "endSection": "title" }, { "offsetInBeginSection": 8, "offsetInEndSection": 114, "text": "progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341507", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 205, "text": "Anti-citrullinated peptide antibodies (ACPA) and the C1858T missense single-nucleotide polymorphism (SNP) in the PTPN22 gene are both associated with the development of rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17666451", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 155, "text": "HLA-DRB1 shared epitope (HLA-SE), PTPN22 and CTLA4 alleles are associated with cyclic citrullinated peptide (CCP) and rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17666451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Auto-antibodies, HLA and PTPN22: susceptibility markers for rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18156150", "endSection": "title" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1209, "text": "The combination of the PTPN22 1858T variant and anti-CCP antibodies gave a high specificity for the disease, and was significantly associated with RA (P = 8.86 x 10(-5), OR 10.05, 95% CI 1.88-53.73)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18156150", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1442, "text": "The combination of the T variant of the 1858 polymorphism of the PTPN22 gene in combination with the presence of anti-CCP antibodies, preferentially in a SE-positive individual, is associated with the development of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18156150", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1422, "text": "No association of the PTPN22 gene with mortality was detected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18240242", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 744, "text": "Cox proportional hazards regression models were used to assess the association of the HLA-DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti-cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18240242", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 338, "text": "The disease association of the common 1858C>T Arg620Trp (rs2476601) nonsynonymous single nucleotide polymorphism (SNP) of protein tyrosine phosphatase; nonreceptor type 22 (PTPN22) on chromosome 1p13 has been confirmed in type 1 diabetes and also in other autoimmune diseases, including rheumatoid arthritis and Graves' disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18305142", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 242, "text": "To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18398946", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 99, "text": "PTPN22, PADI-4, and CTLA-4 have been associated with risk for rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462498", "endSection": "abstract" }, { "offsetInBeginSection": 1986, "offsetInEndSection": 2105, "text": "A significant multiplicative interaction between PTPN22 and smoking for more than 10 pack-years was observed (P = 0.04)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462498", "endSection": "abstract" }, { "offsetInBeginSection": 2330, "offsetInEndSection": 2393, "text": "No gene-gene interaction was observed between PTPN22 and HLA-SE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462498", "endSection": "abstract" }, { "offsetInBeginSection": 2408, "offsetInEndSection": 2635, "text": "After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts. We found both additive and multiplicative interactions between PTPN22 and heavy cigarette smoking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462498", "endSection": "abstract" }, { "offsetInBeginSection": 2408, "offsetInEndSection": 2535, "text": "After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462498", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 973, "text": "Weak evidence for an effect at the PTPN22 locus was also observed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921970", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Association of the PTPN22 gene (-1123G > C) polymorphism with rheumatoid arthritis in Chinese patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20604892", "endSection": "title" }, { "offsetInBeginSection": 593, "offsetInEndSection": 745, "text": "These data suggest, the CC genotype and C allele of the -1123G > C in the PTPN22 gene are associated with an increased risk for RA in Chinese population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20604892", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 894, "text": "Therefore, the CC genotype and C allele of the -1123G > C in the PTPN22 gene may be used as a genetic marker for the predisposition of RA in Chines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20604892", "endSection": "abstract" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1606, "text": "A longer duration of breastfeeding increased the risk of developing RA, especially among individuals seropositive for ACPA or IgM-RF or carrying the PTPN22 1858T variant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560812", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1302, "text": "In a multiple logistic regression analysis, increasing time of breastfeeding (OR 9.5, 95% CI 2.14-42.43 for \u2265 17 months), seropositivity for ACPAs (OR 19.5, 95% CI 4.47-84.81), and carriage of the PTPN22 1858T variant (OR 3.2, 95% CI 1.36-7.54) remained significant predictors of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560812", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1496, "text": "After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20498205", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 425, "text": "Recent genome-wide association studies (GWAS) on RA identified known and novel susceptibility genes like HLA-DRB1, PTPN22, STAT4, TRAF1/C5, OLIG3/TNFAIP3, CD40, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, IL2RB, and KIF5A-PIP4K2C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20398001", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 980, "text": "In the total RA inception cohort, the HLA-DRB1 shared epitope (per-allele odds ratio (OR) = 2.1, trend P < 0.0001), PTPN22 (per-allele OR = 1.5, trend P < 0.0001), OLIG3/TNFAIP3 locus (per-allele OR = 1.2, trend P = 0.009) and TRAF1/C5 locus (per-allele OR = 1.1, trend P = 0.04) were associated with RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20353580", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 228, "text": "This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20353580", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 808, "text": "Progress has been made in determining the relative contributions and the interaction of the shared epitope, PTPN22 and smoking in conferring the risk of anticitrullinated protein antibodies-positive and negative RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20061955", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1357, "text": "Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20032229", "endSection": "abstract" }, { "offsetInBeginSection": 1506, "offsetInEndSection": 1575, "text": "Our analyses have confirmed previous findings for genes PTPN22 and C5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20017985", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 997, "text": "Fifty-five percent of the FDRs had > or =1 copy of the shared epitope, 20% had > or =1 copy of the PTPN22 polymorphism, and approximately 16% were positive for rheumatoid factor (RF; including isotypes) and/or anti-cyclic citrullinated peptide antibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19950324", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 747, "text": "As an effect several new genes have been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region polymorphism(s) are among newly identified and already confirmed genetic risk factors, whereas STAT 4, CTLA4, PADI4 and IRF5 genes polymorphisms are listed among probable RA development genetic risk factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19856886", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 626, "text": "After initial completion of the Human Genome Project on the 16th February 2001, significant progress has been made in identifying other than HLA genome regions linked to the increased RA susceptibility. As an effect several new genes have been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region polymorphism(s) are among newly identified and already confirmed genetic risk factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19856886", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 776, "text": "Patients were analysed for anti-MCV and anti-cyclic citrullinated peptide (CCP), and were genotyped for human leukocyte antigen (HLA)-DRB1 \"shared epitope\" (SE) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) 1858T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19648126", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 385, "text": "As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19445664", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1138, "text": "However, we were able to replicate the association signals between RA and HLA-DRB1 alleles, STAT4 (rs7574865), PTPN22 (rs2476601) and OLIG3/TNFAIP3 (rs10499194 and rs6920220)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19445664", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1631, "text": "Additionally, SNPs rs7574865STAT4 (P = 9.2*10-6; OR = 1.71, 95% CI = 1.35 - 2.18) and rs2476601PTPN22 (P = 9.5*10-4; OR = 1.67, 95% CI = 1.23 - 2.26) were associated with susceptibility to RA, whereas after permutation testing OLIG3/TNFAIP3 SNPs rs10499194 and rs6920220 missed our criteria for significance (Pcorr = 0.114 and Pcorr = 0.180, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19445664", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1767, "text": "In our Slovak population, HLA-DRB1 alleles as well as SNPs in STAT4 and PTPN22 genes showed a strong association with RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19445664", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 303, "text": "Recent advances have led to novel identification of genetic polymorphisms that are associated with susceptibility to rheumatoid arthritis (RA). Currently, 5 loci (HLA, PTPN22, TRAF1/C5, TNFAIP3, and STAT4) have been consistently reported, whereas others have been observed less systematically", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404967", "endSection": "abstract" }, { "offsetInBeginSection": 1291, "offsetInEndSection": 1413, "text": "Genetic markers such as shared epitope alleles and PTPN22 1858T variant increase the relative risk for disease development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19365265", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 779, "text": "Particularly, ACPAs in combination with human leukocyte antigen-shared epitope alleles and PTPN22 1858T carriage increased the relative risks of developing RA compared with not having these factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19365265", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 664, "text": "However, inconsistent results of the contributions of non-HLA susceptibility genes have been described, with the exception of a few genes repeatedly associated with RA-susceptibility, such as PTPN22 gene in populations of European ancestry and PADI4 gene in populations of Asian ancestry, revealing the presence of genetic heterogeneity in RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Functional polymorphisms of PTPN22 and FcgR genes in Tunisian patients with rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20707220", "endSection": "title" }, { "offsetInBeginSection": 327, "offsetInEndSection": 398, "text": "We found strong evidence of an association of PTPN22 620W allele and RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20707220", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1015, "text": "In conclusion, we have confirmed that PTPN22 620W allele is associated with Tunisian RA but does not constitute a factor influencing clinical manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20707220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The C1858T allele of the PTPN22 gene has been reported to confer risk for RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19034456", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1376, "text": "Similarly, the presence or absence of the HLA-DRB1 shared epitope or the RA-associated PTPN22 allele had no influence on this association", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812394", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 281, "text": "Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648537", "endSection": "abstract" }, { "offsetInBeginSection": 1656, "offsetInEndSection": 1823, "text": "Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18648537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anti-citrullinated protein antibodies to very early rheumatoid arthritis diagnosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18535030", "endSection": "title" }, { "offsetInBeginSection": 1248, "offsetInEndSection": 1485, "text": "PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the predictive value of RF and ACPA for RA diagnosis in our cohort, and do not contribute to an earlier diagnosis in undifferentiated patients initially negative for RF and ACPA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18535030", "endSection": "abstract" } ] }, { "body": "Is marijuana use associated with increased risk for stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15801396", "http://www.ncbi.nlm.nih.gov/pubmed/23160887", "http://www.ncbi.nlm.nih.gov/pubmed/23299821", "http://www.ncbi.nlm.nih.gov/pubmed/18025032", "http://www.ncbi.nlm.nih.gov/pubmed/16832776", "http://www.ncbi.nlm.nih.gov/pubmed/22150621", "http://www.ncbi.nlm.nih.gov/pubmed/22107013", "http://www.ncbi.nlm.nih.gov/pubmed/15297005", "http://www.ncbi.nlm.nih.gov/pubmed/1992832", "http://www.ncbi.nlm.nih.gov/pubmed/15060269", "http://www.ncbi.nlm.nih.gov/pubmed/8944217", "http://www.ncbi.nlm.nih.gov/pubmed/12412838", "http://www.ncbi.nlm.nih.gov/pubmed/11462796", "http://www.ncbi.nlm.nih.gov/pubmed/15716544", "http://www.ncbi.nlm.nih.gov/pubmed/11811864", "http://www.ncbi.nlm.nih.gov/pubmed/17432216" ], "ideal_answer": [ "Yes, the use of marijuana is associated with increased risk for ischemic stroke, especially in young adults. The mechanisms underlying such association remain largely unclear, but increased vascular reactivity and increased cerebrovascular resistance were implicated." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008385", "http://www.disease-ontology.org/api/metadata/DOID:3455", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012307", "http://www.disease-ontology.org/api/metadata/DOID:9505", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002189", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002188", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020521" ], "type": "yesno", "id": "5149e23dd24251bc0500004b", "snippets": [ { "offsetInBeginSection": 305, "offsetInEndSection": 504, "text": "The illicit drugs more commonly associated with stroke are psychomotor stimulants, such as amphetamine and cocaine. Less commonly implicated are opioids and psychotomimetic drugs, including cannabis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23299821", "endSection": "sections.0" }, { "offsetInBeginSection": 565, "offsetInEndSection": 805, "text": "Among 326 patients (184 males), the most frequent stroke risk factors overall were dyslipidaemia (187), smoking (161), hypertension (105) and obesity (92). Fifty-one patients used illicit drugs, mostly comprising marijuana and amphetamines.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22107013", "endSection": "sections.0" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1611, "text": "Patients in Adelaide are more likely to be obese, to be misusing marijuana and amphetamines, to suffer a cardioembolic event and to have a stroke that concurrently affects both the anterior and posterior cerebral circulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22107013", "endSection": "sections.0" }, { "offsetInBeginSection": 511, "offsetInEndSection": 741, "text": "RCVS was spontaneous in 37% of patients and secondary in the 63% others, to postpartum in 5 and to exposure to various vasoactive substances in 37, mainly cannabis, selective serotonin-recapture inhibitors and nasal decongestants.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025032", "endSection": "sections.0" }, { "offsetInBeginSection": 219, "offsetInEndSection": 463, "text": "We reported two cases of young stroke associated with drug misuse. Case 1 used amphetamine, cocaine, marijuana and LSD for few yaers, and developed occlusion of a middle cerebral artery. Case 2 presented aphasia shortly after marijuana smoking.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17432216", "endSection": "sections.0" }, { "offsetInBeginSection": 558, "offsetInEndSection": 673, "text": "Marijuana may have accelerated stroke onset, but essential cause of stroke in this case must be protein S mutation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17432216", "endSection": "sections.0" }, { "offsetInBeginSection": 93, "offsetInEndSection": 238, "text": "Cannabis is the most widely consumed among the illicit drugs worldwide, but it has only exceptionally been associated to cerebrovascular disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16832776", "endSection": "sections.0" }, { "offsetInBeginSection": 248, "offsetInEndSection": 395, "text": "We here describe 2 young patients (26 and 29 years, respectively) who suffered from ischemic stroke in temporal relation with cannabis consumption.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16832776", "endSection": "sections.0" }, { "offsetInBeginSection": 409, "offsetInEndSection": 523, "text": "The review of the literature on this topic reveals another 18 patients with stroke in association to cannabis use.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16832776", "endSection": "sections.0" }, { "offsetInBeginSection": 573, "offsetInEndSection": 725, "text": "Although a causal relationship is difficult to establish due to the widespread use of cannabis, this drug may play an etiologic role in ischemic stroke.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16832776", "endSection": "sections.0" }, { "offsetInBeginSection": 243, "offsetInEndSection": 319, "text": "Marijuana may trigger a myocardial infarction and have a vasospastic effect.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801396", "endSection": "sections.0" }, { "offsetInBeginSection": 97, "offsetInEndSection": 244, "text": "Despite the fact that cannabis is the most widely used illicit drug, there are only a few reports associating its use with cerebrovascular disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716544", "endSection": "sections.0" }, { "offsetInBeginSection": 245, "offsetInEndSection": 343, "text": "We describe a patient who suffered three ischaemic strokes immediately after cannabis consumption.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716544", "endSection": "sections.0" }, { "offsetInBeginSection": 596, "offsetInEndSection": 697, "text": "Cannabis use may be associated with ischaemic stroke in young patients, but its mechanism is unclear.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15716544", "endSection": "sections.0" }, { "offsetInBeginSection": 95, "offsetInEndSection": 292, "text": "A right occipital ischemic stroke occurred in a 37-year-old Albanese man with a previously uneventful medical history, 15 min after having smoked a cigarette with approximately 250 mg of marijuana.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15297005", "endSection": "sections.0" }, { "offsetInBeginSection": 716, "offsetInEndSection": 1019, "text": "Therefore, as the family history for cerebrovascular events, blood pressure, clotting tests, examinations for thrombophilia, vasculitis, extracranial and intracranial arteries and cardiac investigations were normal or respectively negative, the stroke was attributed to the chronic cannabis consumption.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15297005", "endSection": "sections.0" }, { "offsetInBeginSection": 734, "offsetInEndSection": 923, "text": "Three adolescent males had similar presentations of headache, fluctuating level of consciousness or lethargy, visual disturbance, and variable ataxia after self-administration of marijuana.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15060269", "endSection": "sections.0" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1250, "text": "Episodic marijuana use may represent a risk factor for stroke in childhood, particularly in the posterior circulation.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15060269", "endSection": "sections.0" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1159, "text": "Although several mechanisms exist by which marijuana use might contribute to the development of chronic cardiovascular conditions or acutely trigger cardiovascular events, there are few data regarding marijuana/THC use and cardiovascular disease outcomes.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12412838", "endSection": "sections.0" }, { "offsetInBeginSection": 282, "offsetInEndSection": 466, "text": "Reported here is the case of a previously healthy young man who smoked marijuana on a daily basis and had an occipital lobe stroke; he was found to be heterozygous for factor V Leiden.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11811864", "endSection": "sections.0" }, { "offsetInBeginSection": 467, "offsetInEndSection": 628, "text": "This case suggests that marijuana smoking may increase the risk of arterial thrombosis in otherwise healthy individuals who are heterozygous for factor V Leiden.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11811864", "endSection": "sections.0" }, { "offsetInBeginSection": 587, "offsetInEndSection": 654, "text": "Thus, chronic abuse of marijuana might be a risk factor for stroke.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11462796", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "A 22-year-old man with a five-year history of drug and alcohol abuse presented with a left hemiparesis preceded by three transient ischaemic attacks, two of which occurred whilst smoking cannabis. Substance abuse was the only identifiable risk factor for cerebrovascular disease.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8944217", "endSection": "sections.0" }, { "offsetInBeginSection": 928, "offsetInEndSection": 984, "text": "Chronic marijuana smoking, however, seems to reduce CBF.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1992832", "endSection": "sections.0" }, { "offsetInBeginSection": 1687, "offsetInEndSection": 2185, "text": "Research directions might include more studies of cardiovascular disease outcomes and relationships of marijuana with cardiovascular risk factors, studies of metabolic and physiologic effects of chronic marijuana use that may affect cardiovascular disease risk, increased understanding of the role of the cannabinoid receptor system in cardiovascular regulation, and studies to determine if there is a therapeutic role for cannabinoids in blood pressure control or for neuroprotection after stroke.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12412838", "endSection": "sections.0" } ] }, { "body": "How many and which are the different isoforms for the ryanodine receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18221109", "http://www.ncbi.nlm.nih.gov/pubmed/19503748", "http://www.ncbi.nlm.nih.gov/pubmed/17707769", "http://www.ncbi.nlm.nih.gov/pubmed/14592807", "http://www.ncbi.nlm.nih.gov/pubmed/17526017", "http://www.ncbi.nlm.nih.gov/pubmed/24521037", "http://www.ncbi.nlm.nih.gov/pubmed/20961976", "http://www.ncbi.nlm.nih.gov/pubmed/18005397" ], "ideal_answer": [ "Generally, three ryanodine receptor isoforms (RyR1-RyR3) are known. RyR1, expressed in skeletal muscle; RyR2, expressed in cardiac muscle; and RyR3, expressed in various cells. RyR3 is preferentially expressed in the brain especially in the hippocampus and striatum." ], "exact_answer": [ [ "Ryanodine Receptor type 1", "RyR1" ], [ "Ryanodine Receptor type 2", "RyR2" ], [ "Ryanodine Receptor type 3", "RyR3" ] ], "type": "list", "id": "54db7217c4c6ce8e1d000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Skeletal (RyR1) and cardiac muscle (RyR2) isoforms of ryanodine receptor calcium channels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24521037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca(2+) from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle. RyRs are the largest known ion channels (> 2MDa) and exist as three mammalian isoforms (RyR 1-3),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20961976", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 446, "text": "Ryanodine receptors (RyRs) are a family of intracellular calcium release channels that mediate calcium-induced calcium release from the endoplasmic reticulum. Among the three RyR isoforms, RyR3 is preferentially expressed in the brain especially in the hippocampus and striatum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19503748", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 573, "text": "In excitable cells such as skeletal and cardiac myocytes excitation-contraction coupling is an important intermediate step between initiation of the action potential and induction of contraction. This process is predominantly controlled by Ca(2+) release from the sarcoplasmic reticulum via the ryanodine receptor. This very large protein (MW 560 kDa) exists as a homotetramer (~2.2 MDa) and is expressed in three isoforms: RyR1, expressed in skeletal muscle; RyR2, expressed in cardiac muscle; and RyR3, expressed in various cells at lower levels than the other isoforms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18221109", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 320, "text": "Generally, three ryanodine receptor isoforms (RyR1-RyR3) are known; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18005397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Ryanodine receptor (RyR) is a Ca(2+) channel that mediates Ca(2+) release from intracellular stores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707769", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 315, "text": "There are three RyR isoforms,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17707769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Ryanodine receptors (RyRs) are intracellular Ca(2+) channels that mediate the release of calcium from internal stores and therefore play an important role in Ca(2+) signaling and homeostasis. Three RyR isoforms have been described thus far,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526017", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 560, "text": "RyR1 and RyR2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526017", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 574, "text": "RyR3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526017", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 393, "text": "Three different isoforms of the SR Ca2+ release channels, or ryanodine receptors (RyRs), have been isolated (RyR1, RyR2, and RyR3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14592807", "endSection": "abstract" } ] }, { "body": "Which compound is a specific inhibitor for Nox1 and Nox4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25656366", "http://www.ncbi.nlm.nih.gov/pubmed/24511132", "http://www.ncbi.nlm.nih.gov/pubmed/22806357", "http://www.ncbi.nlm.nih.gov/pubmed/21419746", "http://www.ncbi.nlm.nih.gov/pubmed/20558727" ], "ideal_answer": [ "GKT136901 is a specific inhibitor of Nox1 and Nox4." ], "exact_answer": [ "GKT136901" ], "concepts": [ "http://www.uniprot.org/uniprot/NOX4_MOUSE", "http://www.uniprot.org/uniprot/NOX4_RAT", "http://www.uniprot.org/uniprot/NOX4_PONAB", "http://www.uniprot.org/uniprot/NOX1_RAT", "http://www.uniprot.org/uniprot/NOX4_HUMAN", "http://www.uniprot.org/uniprot/NOX1_MOUSE" ], "type": "factoid", "id": "56c865d25795f9a73e000016", "snippets": [ { "offsetInBeginSection": 137, "offsetInEndSection": 270, "text": "The efficacy of the Nox1/Nox4 inhibitor GKT137831 on the manifestations of DN was studied in OVE26 mice, a model of type 1 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25656366", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 579, "text": "At both doses, GKT137831 inhibited NADPH oxidase activity, superoxide generation, and hydrogen peroxide production in the renal cortex from diabetic mice without affecting Nox1 or Nox4 protein expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25656366", "endSection": "abstract" }, { "offsetInBeginSection": 1565, "offsetInEndSection": 1761, "text": "GKT136901, a specific inhibitor of Nox1- and Nox4-containing NADPH oxidase activity, attenuated ROS generation and atherosclerosis and decreased CD44 and HA expression in atherosclerotic lesions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20558727", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 504, "text": "Basal NAD(P)H oxidase activity was blocked by GKT136901 (Nox1/4 inhibitor) and by Nox1 siRNA in WKY cells and by siNOX1 and siNOX2 in SHR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21419746", "endSection": "abstract" }, { "offsetInBeginSection": 1565, "offsetInEndSection": 1759, "text": "GKT136901, a specific inhibitor of Nox1- and Nox4-containing NADPH oxidase activity, attenuated ROS generation and atherosclerosis and decreased CD44 and HA expression in atherosclerotic lesions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20558727", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 983, "text": "Importantly, administration of the most specific Nox1/4 inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24511132", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 268, "text": "The efficacy of the Nox1/Nox4 inhibitor GKT137831 on the manifestations of DN was studied in OVE26 mice, a model of type 1 diabetes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25656366", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 985, "text": "Importantly, administration of the most specific Nox1/4 inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24511132", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by the drug Gevokizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24194526", "http://www.ncbi.nlm.nih.gov/pubmed/25108619", "http://www.ncbi.nlm.nih.gov/pubmed/25079039", "http://www.ncbi.nlm.nih.gov/pubmed/22084392", "http://www.ncbi.nlm.nih.gov/pubmed/21048425", "http://www.ncbi.nlm.nih.gov/pubmed/21154167", "http://www.ncbi.nlm.nih.gov/pubmed/23041424", "http://www.ncbi.nlm.nih.gov/pubmed/22699287", "http://www.ncbi.nlm.nih.gov/pubmed/23729309" ], "ideal_answer": [ "Gevokizumab is an allosteric anti-IL-1\u03b2 monoclonal antibody." ], "exact_answer": [ "IL-1\u03b2" ], "type": "factoid", "id": "550e828c71445a662f000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Detailed mechanistic analysis of gevokizumab, an allosteric anti-IL-1\u03b2 antibody with differential receptor-modulating properties.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194526", "endSection": "title" }, { "offsetInBeginSection": 280, "offsetInEndSection": 533, "text": "Gevokizumab is a potent anti-IL-1\u03b2 antibody being developed as a treatment for diseases in which IL-1\u03b2 has been associated with pathogenesis. Previous data indicated that gevokizumab negatively modulates IL-1\u03b2 signaling through an allosteric mechanism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194526", "endSection": "abstract" }, { "offsetInBeginSection": 1575, "offsetInEndSection": 1763, "text": "These data indicate, therefore, that gevokizumab is a unique inhibitor of IL-1\u03b2 signaling that may offer an alternative to current therapies for IL-1\u03b2-associated autoinflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194526", "endSection": "abstract" }, { "offsetInBeginSection": 1484, "offsetInEndSection": 1751, "text": "Most recently, rising evidence reports on the use of adalimumab, etanercept, and golimumab, while use of anti-interleukin (IL)-1 agents (anakinra, canakinumab, gevokizumab), IL-6 blockers (tocilizumab), and rituximab (depleting anti-CD20 antibody) is also increasing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "One target-two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1\u03b2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041424", "endSection": "title" }, { "offsetInBeginSection": 286, "offsetInEndSection": 363, "text": "Canakinumab and gevokizumab are highly specific IL-1\u03b2 monoclonal antibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041424", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 927, "text": "Gevokizumab is claimed to be a regulatory therapeutic antibody that modulates IL-1\u03b2 bioactivity by reducing the affinity for its IL-1RI:IL-1RAcP signaling complex. How IL-1\u03b2 signaling is affected by both canakinumab and gevokizumab was not yet experimentally determined. We have analyzed the crystal structures of canakinumab and gevokizumab antibody binding fragment (Fab) as well as of their binary complexes with IL-1\u03b2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041424", "endSection": "abstract" }, { "offsetInBeginSection": 1603, "offsetInEndSection": 1815, "text": "In contrast, gevokizumab occupies an allosteric site on IL-1\u03b2 and complex formation results in a minor reduction of binding affinity to IL-1RI. This suggests two different mechanisms of IL-1\u03b2 pathway attenuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041424", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 215, "text": "Gevokizumab is a novel, human-engineered monoclonal anti-IL-1\u03b2 antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Interleukin-1\u03b2-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet's disease: an open-label pilot study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22084392", "endSection": "title" }, { "offsetInBeginSection": 131, "offsetInEndSection": 341, "text": "This pilot study aimed to evaluate the safety, pharmacokinetics and clinical activity of XOMA 052 (gevokizumab), a recombinant humanised anti-interleukin 1\u03b2 antibody, in Beh\u00e7et's disease patients with uveitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22084392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Gevokizumab, an anti-IL-1\u03b2 mAb for the potential treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21154167", "endSection": "title" }, { "offsetInBeginSection": 265, "offsetInEndSection": 590, "text": "XOMA is developing gevokizumab (XOMA-052), an IgG2 humanized mAb against human IL-1\u03b2, for the potential treatment of these diseases. Gevokizumab has a high affinity for IL-1\u03b2 and a long t1/2, which would allow for once-monthly dosing and offer a considerable advantage for patients over agents requiring more frequent dosing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21154167", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 771, "text": "To meet these challenges, we developed XOMA 052 (gevokizumab), a potent anti-IL-1\u03b2 neutralizing antibody that was designed in silico and humanized using Human Engineering\u2122 technology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21048425", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 1080, "text": "In the present study, we measured the impact of gevokizumab on the IL-1\u03b2 system using Schild analysis and surface plasmon resonance studies, both of which demonstrated that gevokizumab decreases the binding affinity of IL-1\u03b2 for the IL-1 receptor type I (IL-1RI) signaling receptor, but not the IL-1 counter-regulatory decoy receptor (IL-1 receptor type II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194526", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 360, "text": "Canakinumab and gevokizumab are highly specific IL-1\u03b2 monoclonal antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041424", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 202, "text": "Gevokizumab is a novel, human-engineered monoclonal anti-IL-1\u03b2 antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699287", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 361, "text": "Canakinumab and gevokizumab are highly specific IL-1\u03b2 monoclonal antibodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041424", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 202, "text": "Gevokizumab is a novel, human-engineered monoclonal anti-IL-1\u03b2 antibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699287", "endSection": "abstract" } ] }, { "body": "Which protein phosphatases have been found to dephosphorylate phospholamban?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9350040", "http://www.ncbi.nlm.nih.gov/pubmed/1849481" ], "ideal_answer": [ "The protein phosphatases which dephosphorylate native, sarcoplasmic reticulum (SR)-associated phospholamban were studied in cardiac muscle extracts and in a Triton fraction prepared by detergent extraction of myofibrils, the latter fraction containing 70-80% of the SR-associated proteins present in the tissue. At physiological concentrations of free Mg2+ (1 mM), protein phosphatase 1 (PP1) accounted for approximately 70% of the total phospholamban phosphatase activity in these fractions towards either Ser-16 (the residue labelled by cAMP-dependent protein kinase, PK-A) or Thr-17 (the residue phosphorylated by an SR-associated Ca2+/calmodulin-dependent protein kinase). Protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C) accounted for the remainder of the activity. ", "The protein phosphatases which dephosphorylate native, sarcoplasmic reticulum (SR)-associated phospholamban were studied in cardiac muscle extracts and in a Triton fraction prepared by detergent extraction of myofibrils, the latter fraction containing 70-80% of the SR-associated proteins present in the tissue. At physiological concentrations of free Mg2+ (1 mM), protein phosphatase 1 (PP1) accounted for approximately 70% of the total phospholamban phosphatase activity in these fractions towards either Ser-16 (the residue labelled by cAMP-dependent protein kinase, PK-A) or Thr-17 (the residue phosphorylated by an SR-associated Ca2+/calmodulin-dependent protein kinase). Protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C) accounted for the remainder of the activity." ], "exact_answer": [ [ "Protein Phosphatase 1", "PP1" ], [ "Protein phosphatase 2A", "PP2A" ], [ "Protein Phosphatase 2C", "PP2C" ], [ "Protein Phosphatase 2B", "PP2B" ] ], "type": "list", "id": "5506a7a48e1671127b000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 785, "text": "The protein phosphatases which dephosphorylate native, sarcoplasmic reticulum (SR)-associated phospholamban were studied in cardiac muscle extracts and in a Triton fraction prepared by detergent extraction of myofibrils, the latter fraction containing 70-80% of the SR-associated proteins present in the tissue. At physiological concentrations of free Mg2+ (1 mM), protein phosphatase 1 (PP1) accounted for approximately 70% of the total phospholamban phosphatase activity in these fractions towards either Ser-16 (the residue labelled by cAMP-dependent protein kinase, PK-A) or Thr-17 (the residue phosphorylated by an SR-associated Ca2+/calmodulin-dependent protein kinase). Protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C) accounted for the remainder of the activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1849481", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1885, "text": "These results are consistent with the views that protein phosphatase 1 is capable of dephosphorylating membrane-associated phospholamban when it is phosphorylated by protein kinase A, but not by calcium/calmodulin kinase, and that under certain conditions, calcium/calmodulin-stimulated protein phosphatase (protein phosphatase 2B) is also able to dephosphorylate PLN phosphorylated by protein kinase A. Additionally, the observations show that protein phosphatase 1 is extremely active against the three protein kinase A substrates (M(r) 23, 19 and 17 kDa) that were present in the isolated microsomes and whose state of phosphorylation was particularly affected in the presence of dimethylsulfoxide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9350040", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1585, "text": "These results are consistent with the views that protein phosphatase 1 is capable of dephosphorylating membrane-associated phospholamban when it is phosphorylated by protein kinase A, but not by calcium/calmodulin kinase, and that under certain conditions, calcium/calmodulin-stimulated protein phosphatase (protein phosphatase 2B) is also able to dephosphorylate PLN phosphorylated by protein kinase A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9350040", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1586, "text": "These results are consistent with the views that protein phosphatase 1 is capable of dephosphorylating membrane-associated phospholamban when it is phosphorylated by protein kinase A, but not by calcium/calmodulin kinase, and that under certain conditions, calcium/calmodulin-stimulated protein phosphatase (protein phosphatase 2B) is also able to dephosphorylate PLN phosphorylated by protein kinase A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9350040", "endSection": "abstract" } ] }, { "body": "What is the most prominent sequence consensus for the polyadenylation site?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1993703", "http://www.ncbi.nlm.nih.gov/pubmed/2513486", "http://www.ncbi.nlm.nih.gov/pubmed/1712333", "http://www.ncbi.nlm.nih.gov/pubmed/1915889", "http://www.ncbi.nlm.nih.gov/pubmed/7901430", "http://www.ncbi.nlm.nih.gov/pubmed/6194440" ], "ideal_answer": [ "Functional polyadenylation [poly(A)] sites consist of two sequence elements, the AAUAAA and G/U box signals, that closely flank the site of mRNA 3'-end formation. The canonical polyadenylation signal sequence AATAAA" ], "exact_answer": [ [ "AATAAA" ], [ "AAUAAA" ] ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=1900363", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043631", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039104", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026723", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011063", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011061", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016384", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039221" ], "type": "list", "id": "5133b9455274a5fb0700000c", "snippets": [ { "offsetInBeginSection": 364, "offsetInEndSection": 417, "text": "the cannonical polyadenylation signal sequence AATAAA", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1915889", "endSection": "sections.0" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1235, "text": "Two AATAAA motifs are coded in the last exon of this gene", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1993703", "endSection": "sections.0" }, { "offsetInBeginSection": 236, "offsetInEndSection": 407, "text": "The results demonstrate that the intact AAUAAA is not required for RNA polyadenylation but is required for the cleavage step preceding polyadenylation to occur efficiently", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6194440", "endSection": "sections.0" }, { "offsetInBeginSection": 464, "offsetInEndSection": 532, "text": "the early poly(A) consensus signal was mutated from AAUAAA to UGUAAA", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7901430", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Functional polyadenylation [poly(A)] sites consist of two sequence elements, the AAUAAA and G/U box signals, that closely flank the site of mRNA 3'-end formation", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1712333", "endSection": "sections.0" }, { "offsetInBeginSection": 849, "offsetInEndSection": 944, "text": "the appropriate spacing of the AAUAAA and G/U box signals is critical for poly(A) site function", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1712333", "endSection": "sections.0" }, { "offsetInBeginSection": 189, "offsetInEndSection": 320, "text": " Two AATAAA hexanucleotide sequences are present in the 2092 nucleotide interval. The first one functions as the major polyA signal", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2513486", "endSection": "sections.0" } ] }, { "body": "Does fibronectin constitute a serum biomarker for Duchenne muscular dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24458521" ], "ideal_answer": [ "Compared to age-matched controls, fibronectin levels in DMD patients were found to be significantly increased, whereas in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were close to the control levels. Additionally, progressive elevation in fibronectin levels was observed in longitudinal samples from DMD patients followed up for a period of 6 months up to 4 years. Therefore, fibronectin is a serum biomarker for Duchenne muscular dystrophy.", "Fibronectin is a serum biomarker for Duchenne muscular dystrophy" ], "exact_answer": "yes", "type": "yesno", "id": "5715c16dcb4ef8864c000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Fibronectin is a serum biomarker for Duchenne muscular dystrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "title" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1186, "text": "There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls. Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels. Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1355, "text": "This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Fibronectin is a serum biomarker for Duchenne muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "title" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1356, "text": "Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years.CONCLUSION AND CLINICAL RELEVANCE: This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 859, "text": "There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1150, "text": "Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1285, "text": "This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1286, "text": "Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years. This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1381, "text": "This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients. \u00a9 2014 The Authors PROTEOMICS - Clinical Applications Published by Wiley-VCH Verlag GmbH & Co.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 997, "text": "There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls. Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1151, "text": "Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels. Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Fibronectin is a serum biomarker for Duchenne muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "title" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1286, "text": "This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458521", "endSection": "abstract" } ] }, { "body": "What colonoscopy findings have been reported in autism", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11241044", "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "http://www.ncbi.nlm.nih.gov/pubmed/19214283", "http://www.ncbi.nlm.nih.gov/pubmed/11007230" ], "ideal_answer": [ "Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls." ], "type": "summary", "id": "5509ce9ec2af5d5b70000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Autistic enterocolitis: fact or fiction?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214283", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 565, "text": "There have been several reports of a link between autism and chronic gastrointestinal symptoms. Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19214283", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 258, "text": "Intestinal mucosal pathology, characterized by ileo-colonic lymphoid nodular hyperplasia (LNH) and mild acute and chronic inflammation of the colorectum, small bowel and stomach, has been reported in children with autistic spectrum disorder (ASD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 614, "text": "One hundred and forty-eight consecutive children with ASD (median age 6 years; range 2-16; 127 male) with gastrointestinal symptoms were investigated by ileo-colonoscopy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "endSection": "abstract" }, { "offsetInBeginSection": 2160, "offsetInEndSection": 2487, "text": "Ileo-colonic LNH is a characteristic pathological finding in children with ASD and gastrointestinal symptoms, and is associated with mucosal inflammation. Differences in age at colonoscopy and diet do not account for these changes. The data support the hypothesis that LNH is a significant pathological finding in ASD children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 355, "text": "Ileo-colonoscopy was performed in 21 consecutively evaluated children with autistic spectrum disorders and bowel symptoms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11241044", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1685, "text": "Immunohistochemistry confirms a distinct lymphocytic colitis in autistic spectrum disorders in which the epithelium appears particularly affected. This is consistent with increasing evidence for gut epithelial dysfunction in autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11241044", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 751, "text": " Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "endSection": "abstract" }, { "offsetInBeginSection": 2061, "offsetInEndSection": 2171, "text": "A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "endSection": "abstract" }, { "offsetInBeginSection": 1265, "offsetInEndSection": 1412, "text": "Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "endSection": "abstract" } ] }, { "body": "What is a disordered protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25968230", "http://www.ncbi.nlm.nih.gov/pubmed/25387963", "http://www.ncbi.nlm.nih.gov/pubmed/26301226", "http://www.ncbi.nlm.nih.gov/pubmed/26195786", "http://www.ncbi.nlm.nih.gov/pubmed/26417545", "http://www.ncbi.nlm.nih.gov/pubmed/25715079", "http://www.ncbi.nlm.nih.gov/pubmed/26015579" ], "ideal_answer": [ "Intrinsically disordered proteins lack stable tertiary and/or secondary structures under physiological conditions in vitro. Intrinsically disordered proteins undergo significant conformational transitions to well folded forms only on binding to partner." ], "concepts": [ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016485" ], "type": "summary", "id": "56d12d643975bb303a000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Intrinsically disordered proteins (IDPs) are ubiquitously involved in cellular processes and often implicated in human pathological conditions. The critical biological roles of these proteins, despite not adopting a well-defined fold, encouraged structural biologists to revisit their views on the protein structure-function paradigm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26301226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Intrinsically disordered proteins (IDPs) frequently function in protein interaction networks that regulate crucial cellular signaling pathways. Many IDPs undergo transitions from disordered conformational ensembles to folded structures upon binding to their cellular targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26195786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "The intrinsically disordered protein (IDP) stathmin plays an important regulatory role in cytoskeletal maintenance through its helical binding to tubulin and microtubules. However, it lacks a stable fold in the absence of its binding partner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25715079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Intrinsically disordered proteins lack stable tertiary and/or secondary structures under physiological conditions in vitro. Intrinsically disordered proteins undergo significant conformational transitions to well folded forms only on binding to partner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25387963", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1655, "text": "DisCons is an openly accessible sequence analysis tool that identifies and highlights structurally disordered segments of proteins where the conformational flexibility is conserved across homologs, and therefore potentially functional. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25968230", "endSection": "abstract" } ] }, { "body": "What is the Drosophila melanogaster Groucho protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19250647", "http://www.ncbi.nlm.nih.gov/pubmed/18254933", "http://www.ncbi.nlm.nih.gov/pubmed/21666599", "http://www.ncbi.nlm.nih.gov/pubmed/22319573", "http://www.ncbi.nlm.nih.gov/pubmed/17624551", "http://www.ncbi.nlm.nih.gov/pubmed/16508633", "http://www.ncbi.nlm.nih.gov/pubmed/15861397", "http://www.ncbi.nlm.nih.gov/pubmed/17643306", "http://www.ncbi.nlm.nih.gov/pubmed/22305159", "http://www.ncbi.nlm.nih.gov/pubmed/21429299", "http://www.ncbi.nlm.nih.gov/pubmed/19101520", "http://www.ncbi.nlm.nih.gov/pubmed/19956621", "http://www.ncbi.nlm.nih.gov/pubmed/18721877", "http://www.ncbi.nlm.nih.gov/pubmed/20405012", "http://www.ncbi.nlm.nih.gov/pubmed/18034187", "http://www.ncbi.nlm.nih.gov/pubmed/24086079" ], "ideal_answer": [ "Groucho proteins are abundant and broadly expressed nuclear factors that lack intrinsic DNA-binding activity but can interact with a variety of DNA-binding proteins. The recruitment of Groucho to specific gene regulatory sequences results in transcriptional repression.\nGroucho (Gro) is a Drosophila melanogaster transcriptional corepressor." ], "exact_answer": [ "Groucho (Gro) is a Drosophila melanogaster transcriptional corepressor" ], "concepts": [ "http://www.uniprot.org/uniprot/TLE4_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.uniprot.org/uniprot/GROU_DROME", "http://www.uniprot.org/uniprot/TLE1_MOUSE", "http://www.uniprot.org/uniprot/TLE6_MOUSE", "http://www.uniprot.org/uniprot/TLE1_DANRE", "http://www.uniprot.org/uniprot/TLE2_DANRE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003674", "http://www.uniprot.org/uniprot/TLE4_MOUSE" ], "type": "factoid", "id": "54f608f85f206a0c06000007", "snippets": [ { "offsetInBeginSection": 168, "offsetInEndSection": 361, "text": "Although a repressor could function by recruiting just a single co-repressor, many can recruit more than one, with Drosophila Brinker (Brk) recruiting the co-repressors CtBP and Groucho (Gro), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Groucho (Gro) is a Drosophila corepressor required by numerous DNA-binding repressors, many of which are distributed in gradients and provide positional information during development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22319573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Drosophila Groucho (Gro) is the founding member of a family of metazoan corepressors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22305159", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 475, "text": "Tcf3 requires corepressor molecules such as Groucho (Gro)/TLE and HDAC1 for activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21666599", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 378, "text": "We identified the transcriptional co-repressor xTLE1/Groucho as an EphrinB1 interacting protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21429299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Groucho (Gro) is a Drosophila melanogaster transcriptional corepressor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20405012", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 251, "text": "Transcriptional co-repressors of the Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate the expression of a variety of genes and are involved in numerous developmental processes in both invertebrate and vertebrate species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19956621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The proteins termed TLE in humans, Grg in mice and Groucho in Drosophila constitute a family of transcriptional corepressors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15861397", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 250, "text": "Groucho (Gro)/TLE, a global developmental corepressor, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16508633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "The Groucho/Tle family of corepressor proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17624551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Groucho proteins are abundant and broadly expressed nuclear factors that lack intrinsic DNA-binding activity but can interact with a variety of DNA-binding proteins. The recruitment of Groucho to specific gene regulatory sequences results in transcriptional repression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17643306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The Groucho (Gro)/transducin-like enhancer of split family of transcriptional corepressors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18034187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The Drosophila Groucho (Gro) protein was the founding member of the family of transcriptional co-repressor proteins that now includes the transducin-like enhancer of split (TLE) and Grorelated gene (Grg) proteins in vertebrate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18254933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Groucho/TLE proteins are global corepressors that are recruited to target promoters by different families of DNA-binding repressors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18721877", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by Imetelstat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24409321", "http://www.ncbi.nlm.nih.gov/pubmed/25441685", "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "http://www.ncbi.nlm.nih.gov/pubmed/26332545", "http://www.ncbi.nlm.nih.gov/pubmed/26332546", "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "http://www.ncbi.nlm.nih.gov/pubmed/25627551", "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "http://www.ncbi.nlm.nih.gov/pubmed/20048334", "http://www.ncbi.nlm.nih.gov/pubmed/25120190", "http://www.ncbi.nlm.nih.gov/pubmed/24097866" ], "ideal_answer": [ "Imetelstat works by inhibiting telomerase." ], "exact_answer": [ "telomerase" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ], "type": "factoid", "id": "56c048acef6e39474100001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2+ breast cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25627551", "endSection": "title" }, { "offsetInBeginSection": 443, "offsetInEndSection": 635, "text": "The purpose of this study was to investigate the effects of a telomerase antagonistic oligonucleotide, imetelstat (GRN163L), on CSC and non-CSC populations of HER2(+) breast cancer cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25627551", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1011, "text": "Imetelstat inhibited telomerase activity in both subpopulations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25627551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Telomerase inhibitor Imetelstat (GRN163L) limits the lifespan of human pancreatic cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24409321", "endSection": "title" }, { "offsetInBeginSection": 199, "offsetInEndSection": 334, "text": "GRN163L (Imetelstat) is a lipid-conjugated N3'\u2192P5' thio-phosphoramidate oligonucleotide that blocks the template region of telomerase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24409321", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 301, "text": "We evaluated the effect of the telomerase inhibitor imetelstat in preclinical models of MRT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25441685", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 875, "text": "Treatment with imetelstat resulted in inhibition of telomerase activity, marked telomere shortening, and activation of the DNA damage response pathway, as measured by formation of \u03b3-H2AX nuclear foci, phosphorylation of ATM, and phosphorylation of TP53.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25441685", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1278, "text": "The activity of imetelstat as a single agent suggests that further studies of telomerase inhibitors in combination with other agents may be warranted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25441685", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1121, "text": " Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25120190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "PURPOSE: Imetelstat is a covalently-lipidated 13-mer thiophosphoramidate oligonucleotide that acts as a potent specific inhibitor of telomerase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097866", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1068, "text": "Imetelstat inhibited telomerase activity in both subpopulations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25627551", "endSection": "abstract" }, { "offsetInBeginSection": 1603, "offsetInEndSection": 1712, "text": "Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25120190", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 539, "text": "Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "endSection": "abstract" }, { "offsetInBeginSection": 765, "offsetInEndSection": 931, "text": "When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1850, "text": "Differences between telomerase activity expression levels or telomere length of CSCs and bulk tumor cells in these cell lines did not correlate with the increased sensitivity of CSCs to imetelstat, suggesting a mechanism of action independent of telomere shortening for the effects of imetelstat on the CSC subpopulations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Imetelstat (a telomerase antagonist) exerts off\u2011target effects on the cytoskeleton.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "endSection": "title" }, { "offsetInBeginSection": 546, "offsetInEndSection": 733, "text": "The GBM tumor-initiating cells were treated with imetelstat and examined for the effects on telomerase activity levels, telomere length, proliferation, clonogenicity, and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048334", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 390, "text": "We evaluated the effect of the telomerase inhibitor imetelstat in preclinical models of MRT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25441685", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 479, "text": "This enzyme is expressed in approximately 90% of human tumors, but not in the majority of normal somatic cells. imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'\u2192P5' thio-phosphoramidate lipid conjugate, which represents the latest generation of telomerase inhibitors targeting the template region of the human functional telomerase RNA (hTR) subunit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "endSection": "title" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1702, "text": "Our results suggest that imetelstat-mediated depletion of CSCs may offer an alternative mechanism by which telomerase inhibition may be exploited for cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1202, "text": "Imetelstat inhibited telomerase activity in both subpopulations. Moreover, imetelstat alone and in combination with trastuzumab reduced the CSC fraction and inhibited CSC functional ability, as shown by decreased mammosphere counts and invasive potential. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25627551", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 770, "text": "When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 423, "text": "Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26332546", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26332545", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 303, "text": "We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 603, "text": "In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "abstract" }, { "offsetInBeginSection": 1214, "offsetInEndSection": 1537, "text": "Differences between telomerase activity expression levels or telomere length of CSCs and bulk tumor cells in these cell lines did not correlate with the increased sensitivity of CSCs to imetelstat, suggesting a mechanism of action independent of telomere shortening for the effects of imetelstat on the CSC subpopulations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "BACKGROUND: Imetelstat, a 13-mer oligonucleotide that is covalently modified with lipid extensions, competitively inhibits telomerase enzymatic activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26332546", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 470, "text": "Imetelstat is a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase reverse transcriptase.METHODS: We sought to obtain preliminary information on the therapeutic activity and safety of imetelstat in patients with high-risk or intermediate-2-risk myelofibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26332545", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 443, "text": "Telomerase is reactivated in tumor cells, including CSCs, but has limited activity in normal tissues, providing potential for telomerase inhibition in anti-cancer therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25627551", "endSection": "abstract" } ] }, { "body": "What is the catalytic mechanism of DNA (cytosine-5) methyltransferases? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3558369", "http://www.ncbi.nlm.nih.gov/pubmed/16606828", "http://www.ncbi.nlm.nih.gov/pubmed/6884360", "http://www.ncbi.nlm.nih.gov/pubmed/9207015", "http://www.ncbi.nlm.nih.gov/pubmed/11087417", "http://www.ncbi.nlm.nih.gov/pubmed/18567810", "http://www.ncbi.nlm.nih.gov/pubmed/8441638", "http://www.ncbi.nlm.nih.gov/pubmed/21163962", "http://www.ncbi.nlm.nih.gov/pubmed/8441637", "http://www.ncbi.nlm.nih.gov/pubmed/9925782", "http://www.ncbi.nlm.nih.gov/pubmed/8772199", "http://www.ncbi.nlm.nih.gov/pubmed/16926025", "http://www.ncbi.nlm.nih.gov/pubmed/1598200", "http://www.ncbi.nlm.nih.gov/pubmed/12787669", "http://www.ncbi.nlm.nih.gov/pubmed/9576871", "http://www.ncbi.nlm.nih.gov/pubmed/16472822", "http://www.ncbi.nlm.nih.gov/pubmed/16681387", "http://www.ncbi.nlm.nih.gov/pubmed/7473738", "http://www.ncbi.nlm.nih.gov/pubmed/23528166" ], "triples": [ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413849585033007", "o": "Cytosine-C5 specific DNA methyltransferase" } ], "ideal_answer": [ "The catalytic mechanism of the DNA (Cytosine-5-)-methyltransferase involves nucleophilic attack of the C6 of the substrate cytosine by the single conserved cysteine of the enzyme, followed by C5 nucleophilic replacement of the methyl group of the cofactor S-adenosyl-L-methionine (AdoMet) to produce 5-methyl-6-Cys-81-S-5,6-dihydrocytosine. It has been also demonstrated that Phe and Glu, which are found in the catalytic motifs I and II of the enzyme are important for AdoMet binding and catalysis." ], "concepts": [ "http://www.uniprot.org/uniprot/DCM_ECO57", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0051720", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0009008", "http://www.uniprot.org/uniprot/CMT1_DICDI", "http://www.uniprot.org/uniprot/DCM_ECOLI", "http://www.uniprot.org/uniprot/DNMT_FRG3G", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0051719", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003886" ], "type": "summary", "id": "515da5b5298dcd4e5100000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "All DNA (cytosine-5)-methyltransferases contain a single conserved cysteine. It has been proposed that this cysteine initiates catalysis by attacking the C6 of cytosine and thereby activating the normally inert C5 position.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8441637", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Kinetic and catalytic mechanism of HhaI methyltransferase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3558369", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "Kinetic and catalytic properties of the DNA (cytosine-5)-methyltransferase HhaI are described. With poly(dG-dC) as substrate, the reaction proceeds by an equilibrium (or processive) ordered Bi-Bi mechanism in which DNA binds to the enzyme first, followed by S-adenosylmethionine (AdoMet). After methyl transfer, S-adenosylhomocysteine (AdoHcy) dissociates followed by methylated DNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3558369", "endSection": "sections.0" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1268, "text": "Our studies reveal that the catalytic mechanism of DNA (cytosine-5)-methyltransferases involves attack of the C6 of substrate cytosines by an enzyme nucleophile and formation of a transient covalent adduct.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3558369", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12787669", "endSection": "title" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1348, "text": "We propose that correct positioning of the flipped base and the cofactor and binding to the transition state of methyl group transfer are the most important roles of the Dnmt3a enzyme in the catalytic cycle of methyl group transfer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12787669", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "Co-transfections of reporter plasmids and plasmids encoding the catalytic domain of the murine Dnmt3a DNA methyltransferase lead to inhibition of reporter gene expression. As Dnmt3a mutants with C-->A and E-->A exchanges in the conserved PCQ and ENV motifs in the catalytic center of the enzyme also cause repression, we checked for their catalytic activity in vitro.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12787669", "endSection": "sections.0" }, { "offsetInBeginSection": 536, "offsetInEndSection": 730, "text": "In contrast, enzyme variants carrying E-->A, E-->D or E-->Q exchanges of the ENV glutamate are catalytically almost inactive, demonstrating that this residue has a central function in catalysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12787669", "endSection": "sections.0" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1348, "text": "Therefore, covalent complex formation is not essential in the reaction mechanism of Dnmt3a. We propose that correct positioning of the flipped base and the cofactor and binding to the transition state of methyl group transfer are the most important roles of the Dnmt3a enzyme in the catalytic cycle of methyl group transfer.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12787669", "endSection": "sections.0" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1482, "text": "Our results point to a possible connection between the catalytic mechanism of C5 Mtases and of enzymes that transfer methyl groups to N(4) of cytosine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11087417", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Previous X-ray crystallographic studies have revealed that the catalytic domain of a DNA methyltransferase (Mtase) generating C5-methylcytosine bears a striking structural similarity to that of a Mtase generating N6-methyladenine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7473738", "endSection": "sections.0" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1228, "text": "Spontaneous and reversible proton transfer between a conserved Glu in the active site and cytosine N3 at the transition state was observed in our simulations, revealing the chemical participation of this Glu residue in the catalytic mechanism.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23528166", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "The mechanism of DNA cytosine-5-methylation catalyzed by the bacterial M.HhaI enzyme has been considered as a stepwise nucleophilic addition of Cys-81-S- to cytosine C6 followed by C5 nucleophilic replacement of the methyl of S-adenosyl-L-methionine to produce 5-methyl-6-Cys-81-S-5,6-dihydrocytosine.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606828", "endSection": "sections.0" }, { "offsetInBeginSection": 797, "offsetInEndSection": 893, "text": "Hydroxide at 10(-7) mole fraction (pH = 7) is shown to be sufficient for the required catalysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606828", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "On the basis of amino acid sequence alignments and structural data of related enzymes, we have performed a mutational analysis of 14 amino acid residues in the catalytic domain of the murine Dnmt3a DNA-(cytosine C5)-methyltransferase.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16472822", "endSection": "sections.0" }, { "offsetInBeginSection": 616, "offsetInEndSection": 938, "text": "We demonstrate that Phe50 (motif I) and Glu74 (motif II) are important for AdoMet binding and catalysis. D96A (motif III) showed reduced AdoMet binding but increased activity under conditions of saturation with S-adenosyl-L-methionine (AdoMet), indicating that the contact of Asp96 to AdoMet is not required for catalysis.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16472822", "endSection": "sections.0" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1268, "text": "R130A displayed a strong reduction in catalytic activity and a complete change in flanking sequence preferences, indicating that Arg130 has an important role in the DNA interaction of Dnmt3a.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16472822", "endSection": "sections.0" }, { "offsetInBeginSection": 1546, "offsetInEndSection": 1840, "text": "While Asn167 might contribute to the positioning of residues from motif VI, according to structural data Arg202 has a role in catalysis of cytosine-C5 methyltransferases. The R295A variant was catalytically inactive most likely because of destabilization of the hinge sub-domain of the protein.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16472822", "endSection": "sections.0" }, { "offsetInBeginSection": 467, "offsetInEndSection": 603, "text": "These two methyltransferases recognize CpG and GCGC sequences, respectively, and transfer a methyl group to the C5 atom of cytosine (C).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16681387", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Most prokaryotic (cytosine-5)-DNA methyltransferases increase the frequency of deamination at the cytosine targeted for methylation in vitro in the absence of the cofactor S-adenosylmethionine (AdoMet) or the reaction product S-adenosylhomocysteine (AdoHcy).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9576871", "endSection": "sections.0" }, { "offsetInBeginSection": 642, "offsetInEndSection": 844, "text": "The target (methylatable) cytosine, if flipped out of the double helical DNA as seen for DNA methyltransferases that generate 5-methylcytosine, would fit into the concave active site next to the AdoMet.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9207015", "endSection": "sections.0" }, { "offsetInBeginSection": 244, "offsetInEndSection": 462, "text": "These methylation patterns are established and maintained by DNA cytosine-5 methyltransferase (MTase), a approximately 1500 amino acid enzyme containing a regulatory N-terminal domain and a catalytic C-terminal domain.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8772199", "endSection": "sections.0" }, { "offsetInBeginSection": 485, "offsetInEndSection": 749, "text": "These results lend strong support to a catalytic mechanism in which an enzyme sulfhydryl group undergoes Michael addition to the C5-C6 double bond, thus activating position C-5 of the substrate DNA cytosine residue for electrophilic attack by the methyl donor SAM.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8441638", "endSection": "sections.0" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "2'-Deoxyoligonucleotides with 5-fluorocytosine residues incorporated at specific positions of the nucleotide sequence are tools of great potential in the study of the catalytic mechanism by which DNA cytosine methyltransferases methylate the 5-position of DNA cytosine residues in specific sequence contexts.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1598200", "endSection": "sections.0" }, { "offsetInBeginSection": 79, "offsetInEndSection": 201, "text": "The enzyme has Mr 130 000, and introduces methyl groups from S-adenosylmethionine into the 5 position of cytosines in DNA.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6884360", "endSection": "sections.0" } ] }, { "body": "Are mutations in the STXBP1 gene associated with epilepsy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23409955", "http://www.ncbi.nlm.nih.gov/pubmed/21770924", "http://www.ncbi.nlm.nih.gov/pubmed/20845763", "http://www.ncbi.nlm.nih.gov/pubmed/20876469", "http://www.ncbi.nlm.nih.gov/pubmed/21277190", "http://www.ncbi.nlm.nih.gov/pubmed/22709267", "http://www.ncbi.nlm.nih.gov/pubmed/21062273", "http://www.ncbi.nlm.nih.gov/pubmed/24315539", "http://www.ncbi.nlm.nih.gov/pubmed/21364700", "http://www.ncbi.nlm.nih.gov/pubmed/24189369", "http://www.ncbi.nlm.nih.gov/pubmed/21762454", "http://www.ncbi.nlm.nih.gov/pubmed/22787616", "http://www.ncbi.nlm.nih.gov/pubmed/20887364", "http://www.ncbi.nlm.nih.gov/pubmed/22596016", "http://www.ncbi.nlm.nih.gov/pubmed/22612257", "http://www.ncbi.nlm.nih.gov/pubmed/21967765", "http://www.ncbi.nlm.nih.gov/pubmed/19557857", "http://www.ncbi.nlm.nih.gov/pubmed/24095819", "http://www.ncbi.nlm.nih.gov/pubmed/24170257", "http://www.ncbi.nlm.nih.gov/pubmed/18469812", "http://www.ncbi.nlm.nih.gov/pubmed/20493457", "http://www.ncbi.nlm.nih.gov/pubmed/20887371", "http://www.ncbi.nlm.nih.gov/pubmed/23531706", "http://www.ncbi.nlm.nih.gov/pubmed/22787626", "http://www.ncbi.nlm.nih.gov/pubmed/22722545", "http://www.ncbi.nlm.nih.gov/pubmed/21753172", "http://www.ncbi.nlm.nih.gov/pubmed/21204804" ], "ideal_answer": [ "Yes,mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004829", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059645", "http://www.disease-ontology.org/api/metadata/DOID:1826", "http://www.uniprot.org/uniprot/STXB1_PONAB" ], "type": "yesno", "id": "550748a3bde8548216000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Folinic acid responsive epilepsy in Ohtahara syndrome caused by STXBP1 mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24315539", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "A novel mutation in STXBP1 gene in a child with epileptic encephalopathy and an atypical electroclinical pattern.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170257", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, has been reported in Ohtahara syndrome, a rare epileptic encephalopathy with suppression burst pattern on EEG, in patients with infantile spasms and in a few patients with nonsyndromic mental retardation without epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24095819", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 368, "text": "ed with severe developmental delay and poor prognosis. Mutations and deletions in the STXBP1 gene are associated with Ohtahara syndrome, also known as \"early infantile epileptic encephalopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531706", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 382, "text": "Here we show that de novo heterozygous mutations in the gene encoding STXBP1, also known as MUNC18-1, which is essential in synaptic vesicle release in multiple species, cause OS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787616", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1278, "text": "STXBP1 haploinsufficiency results in progressive encephalopathy characterized by intellectual disability and may be accompanied by epilepsy, movement disorders, and autism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Mutations of the syntaxin binding protein 1 (STXBP1) have been associated with severe infantile epileptic encephalopathies (Ohtahara syndrome and West syndrome), but also with moderate to severe cognitive impairment and nonsyndromic epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22596016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "A novel STXBP1 mutation causes focal seizures with neonatal onset.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22596016", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20887364", "endSection": "title" }, { "offsetInBeginSection": 10, "offsetInEndSection": 148, "text": "e novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression-burst pattern (EIEE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20887364", "endSection": "abstract" }, { "offsetInBeginSection": 1876, "offsetInEndSection": 2087, "text": "Mutations in STXBP1 are relatively frequent in patients with infantile epileptic encephalopathies. STXBP1-related encephalopathy may present as drug-responsive infantile spasms with focal/lateralized discharges.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21762454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "De novo SCN1A mutations in migrating partial seizures of infancy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21753172", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18469812", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23409955", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 704, "text": "and STXBP1-related West/Ohtahara syndromes, are due to a mutation in a unique gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787626", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 829, "text": "This is the first case report showing that STXBP1 mutations caused West syndrome from the onset of epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21204804", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of geldanamycin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21525416", "http://www.ncbi.nlm.nih.gov/pubmed/18001136", "http://www.ncbi.nlm.nih.gov/pubmed/9817749", "http://www.ncbi.nlm.nih.gov/pubmed/23986774", "http://www.ncbi.nlm.nih.gov/pubmed/23701727", "http://www.ncbi.nlm.nih.gov/pubmed/15971989", "http://www.ncbi.nlm.nih.gov/pubmed/20534344" ], "ideal_answer": [ "Geldanamycin is an ansamycin antibiotic which holds the ability to bind heat-shock protein 90. This interaction can lead to the disruption of heat-shock protein 90-containing multimolecular complexes. Additionally, it can induce inhibition or even degradation of partner proteins dissociated from the 90 kDa chaperone and, eventually, cause apoptosis in a variety of cell types." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.biosemantics.org/jochem#4250710", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ], "type": "summary", "id": "5319a73cb166e2b806000026", "snippets": [ { "offsetInBeginSection": 932, "offsetInEndSection": 962, "text": "Geldanamycin (HSP90 inhibitor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23986774", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 575, "text": "Geldanamycin is an antibiotic originally discovered based on its ability to bind heat-shock protein 90. This interaction can lead to the disruption of heat-shock protein 90-containing multimolecular complexes. It can also induce the inhibition or even degradation of partner proteins dissociated from the 90 kDa chaperone and, eventually, can cause apoptosis, for instance, in PC12 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23701727", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 849, "text": "An Hsp90 ATPase inhibitor, geldanamycin, inhibits luciferase reactivation demonstrating the importance of the ATP-dependent chaperone activity of E. coli Hsp90 during client protein remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21525416", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 568, "text": "Unique proteome patterns were observed in HeLa cells treated with the HSP90 inhibitor geldanamycin, and were similar to the patterns induced by radicicol, a structurally different HSP90 inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20534344", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 446, "text": "the Hsp90 inhibitor geldanamycin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18001136", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 1342, "text": "The molecular chaperone heat-shock protein (Hsp) 90 is an important anticancer drug target because it maintains the conformation, stability, and function of many important oncogenic client proteins, including those involved with signal transduction, cell proliferation, survival, differentiation, motility angiogenesis, and metastasis. Using the standard inhibitors of the adenosine triphosphatase (ATPase) activity of Hsp90, geldanamycin (GA) and 17-allylamino-17- demethoxygeldanamycin (17AAG), novel solid-phase immunoassays have been validated using a time-resolved fluorescence (TRF) end point. Their utility for confirming the mechanism of action of Hsp90 inhibition in secondary cell-based assays has been shown and applied to the novel Hsp90 inhibitor CCT018159.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15971989", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 568, "text": "A recent crystal structure of the NH2-terminal domain of yeast Hsp90 established the presence of a conserved nucleotide binding site that is identical with the binding site of geldanamycin, a specific inhibitor of Hsp90.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9817749", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 743, "text": "The functional significance of nucleotide binding by Hsp90 has remained unclear. Here we present evidence for a slow but clearly detectable ATPase activity in purified Hsp90.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9817749", "endSection": "abstract" } ] }, { "body": "Which is the most widely used anti-TNF drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21881980", "http://www.ncbi.nlm.nih.gov/pubmed/18420660", "http://www.ncbi.nlm.nih.gov/pubmed/22379032", "http://www.ncbi.nlm.nih.gov/pubmed/19854715", "http://www.ncbi.nlm.nih.gov/pubmed/21177290" ], "ideal_answer": [ "Etanercept is the most widely used anti-TNF drug." ], "exact_answer": [ "Etanercept" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000894", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023201", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044966", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016756", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053199" ], "type": "factoid", "id": "512d0e635274a5fb07000005", "snippets": [ { "offsetInBeginSection": 128, "offsetInEndSection": 249, "text": "higher rates are observed with anti-TNF Abs (e.g., infliximab) as compared with TNF receptor fusion protein (etanercept).", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22379032", "endSection": "sections.0" }, { "offsetInBeginSection": 140, "offsetInEndSection": 201, "text": "Two of them received etanercept and the remainder adalimumab.", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21881980", "endSection": "sections.0" }, { "offsetInBeginSection": 542, "offsetInEndSection": 661, "text": "45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4)", "beginSection": "sections.0", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177290", "endSection": "sections.0" } ] }, { "body": "What is the association between number of pregnancies and rheumatoid arthritis", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2819350", "http://www.ncbi.nlm.nih.gov/pubmed/23070994", "http://www.ncbi.nlm.nih.gov/pubmed/22012422", "http://www.ncbi.nlm.nih.gov/pubmed/10342392", "http://www.ncbi.nlm.nih.gov/pubmed/12839599" ], "ideal_answer": [ "Greater parity significantly reduced the odds of RA. A larger number of pregnancies and late menopause show a protective effect, delaying the onset of the disease." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247" ], "type": "summary", "id": "52f892782059c6d71c000039", "snippets": [ { "offsetInBeginSection": 1230, "offsetInEndSection": 1309, "text": "In this unique population, greater parity significantly reduced the odds of RA;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23070994", "endSection": "abstract" }, { "offsetInBeginSection": 1310, "offsetInEndSection": 1628, "text": "an early age at first birth increased the odds, and the postpartum period was confirmed as high risk for RA onset. The protective effect of repeated exposure to the ameliorating hormonal and immunological changes of pregnancy may counterbalance the effect of early exposure to the postpartum reversal of these changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23070994", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1088, "text": "We found an inverse correlation between the number of pregnancies and age at onset of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22012422", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1311, "text": "A larger number of pregnancies and late menopause show a protective effect, delaying the onset of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22012422", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 205, "text": "Since the landmark study on rheumatoid arthritis, many reports have suggested that physiological changes during pregnancy often induce remission of systemic and cutaneous inflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12839599", "endSection": "abstract" }, { "offsetInBeginSection": 1857, "offsetInEndSection": 2021, "text": "Literature review shows that at best, there are weak negative associations between current estrogen use and RA, and no association with nulliparity and infertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10342392", "endSection": "abstract" }, { "offsetInBeginSection": 2035, "offsetInEndSection": 2494, "text": "It appears that infertility, the number of pregnancies, and pregnancy outcome are not strongly associated with the risk of developing RA in women of childbearing age. However, in this study there may have been selection biases in the women with RA and the controls that differentially could have affected their reproductive outcomes. Thus, a true association could have been missed. Most other published studies find no association between nulliparity and RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10342392", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 949, "text": "Number of pregnancies and children, however, were significantly higher in controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2819350", "endSection": "abstract" } ] }, { "body": "Is mitofusin 2 a receptor for parkin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22807239", "http://www.ncbi.nlm.nih.gov/pubmed/19076450", "http://www.ncbi.nlm.nih.gov/pubmed/22914740", "http://www.ncbi.nlm.nih.gov/pubmed/23958438", "http://www.ncbi.nlm.nih.gov/pubmed/20871098", "http://www.ncbi.nlm.nih.gov/pubmed/21252228", "http://www.ncbi.nlm.nih.gov/pubmed/23620051", "http://www.ncbi.nlm.nih.gov/pubmed/23845246" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1378212", "o": "C111567" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0673396", "o": "http://linkedlifedata.com/resource/umls/label/A8256703" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0673396", "o": "http://linkedlifedata.com/resource/umls/label/A1378212" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0673396", "o": "http://linkedlifedata.com/resource/umls/label/A1378212" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8256703", "o": "parkin protein" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8256703", "o": "5004-0064" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": 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"http://linkedlifedata.com/resource/#_4F39353134300021", "o": "Transmembrane GTPase MFN2" }, { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/Q811U4", "o": "true" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q811U4", "o": "http://linkedlifedata.com/resource/#_5138313155340016" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5138313155340017", "o": "Transmembrane GTPase MFN1" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q811U4", "o": "http://linkedlifedata.com/resource/#_5138313155340017" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5138313155340016", "o": "Mitofusin-1" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/O95140", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0005829" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0005829", "o": "cytosol" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/O95140", "o": "http://purl.uniprot.org/citations/16710414" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/citations/16710414", "o": "Nature" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/16710414", "o": "http://purl.uniprot.org/pubmed/16710414" }, { "p": "http://purl.uniprot.org/core/isolatedFrom", "s": "http://purl.uniprot.org/uniprot/Q811U4", "o": "http://purl.uniprot.org/tissues/1050" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/1050", "o": "Tongue" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/O95140", "o": "MFN2_HUMAN" } ], "ideal_answer": [ "Yes, Mfn2 functions as a mitochondrial receptor for Parkin." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/MFN2_MOUSE", "http://www.uniprot.org/uniprot/PACRG_MOUSE", "http://www.uniprot.org/uniprot/PACRG_HUMAN", "http://www.uniprot.org/uniprot/MFN2_RAT", "http://www.uniprot.org/uniprot/MARF_DROME", "http://www.uniprot.org/uniprot/MFN2_HUMAN" ], "type": "yesno", "id": "5318352fb166e2b806000011", "snippets": [ { "offsetInBeginSection": 113, "offsetInEndSection": 283, "text": "Recent work demonstrates that a phosphorylated form of the mitochondrial fusion protein Mitofusin 2 serves as a receptor for Parkin translocation to damaged mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845246", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 563, "text": "We show that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23620051", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1201, "text": "Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23620051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20871098", "endSection": "title" } ] }, { "body": "What are the main benefits of pharmacophore models?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24245803", "http://www.ncbi.nlm.nih.gov/pubmed/24212027", "http://www.ncbi.nlm.nih.gov/pubmed/24119198", "http://www.ncbi.nlm.nih.gov/pubmed/24287559", "http://www.ncbi.nlm.nih.gov/pubmed/24112046", "http://www.ncbi.nlm.nih.gov/pubmed/22192589", "http://www.ncbi.nlm.nih.gov/pubmed/24294969", "http://www.ncbi.nlm.nih.gov/pubmed/23662282", "http://www.ncbi.nlm.nih.gov/pubmed/20838973", "http://www.ncbi.nlm.nih.gov/pubmed/24140950" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A1308602", "o": "CRISP Thesaurus" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0599740", "o": "http://linkedlifedata.com/resource/umls/label/A1308602" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1308603", "o": "pharmacophore" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0599740", "o": "http://linkedlifedata.com/resource/umls/label/A1308603" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A1308603", "o": "CRISP Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1308603", "o": "2573-1500" } ], "ideal_answer": [ "As researchers continue to search for new targets of therapeutic interest, transmembrane and G-protein coupled receptors are of ever-increasing importance. However, crystal structures for these targets may be impossible to resolve, posing great challenges in rational drug design. Structure-based virtual screening is not an option when the active site geometry is unknown, but assaying an entire library for hits is an inefficient and expensive proposition.\nPharmacophore modeling solves this problem by determining the spatial arrangement of chemical features that confer drug activity toward a target receptor. Having established the chemical space occupied by active ligands, pharmacophore modeling software allows researchers to create 3-D structure-activity relationships, screen databases, and generate hits without the benefit of a receptor structure." ], "exact_answer": [ [ "They represent chemical functions valid not only for the existing bounds but also for unknown molecules." ], [ "Due their simplicity they are proper for large scale virtual screening" ], [ "They are comprehensive and editable, so by changing chemical feature contains information can be easily trace back." ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003198", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008956", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015195", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008961", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008954" ], "type": "list", "id": "532c0ac4d6d3ac6a3400001a", "snippets": [ { "offsetInBeginSection": 149, "offsetInEndSection": 561, "text": "To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between \u03c3(70) and the RNAP core enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24112046", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 1190, "text": "the primary structural features required for estrogen receptor binding, the phenols, are not required for inhibiting parasitic growth. Significantly, the most active antileishmanial benzothiophenes lack the pharmacophore for estrogen receptor activity and therefore address potential concerns about the undesirable effects of using selective estrogen receptor modulators in women and children with leishmaniasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119198", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 255, "text": "series of novel diastereoisomeric \u03c3 ligands 3 was designed, synthesized and pharmacologically evaluated. The highly rigid [4.3.3]propellane scaffold was used to fix the three dimensional orientation of the pharmacophoric moieties required for \u03c3 affinity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24140950", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 988, "text": "This study was performed to identify natural iNOS inhibitors from traditional Chinese herbs through a combination of pharmacophore modeling, molecular docking and virtual screening. First, the pharmacophore models were generated though six known iNOS inhibitors and validated by a test database. The pharmacophore model_017 showed good performance in external validation and was employed to screen Traditional Chinese Medicine Database (Version 2009), which resulting in a hit list of 498 compounds with matching score (QFIT) above 40. Then, the hits were subjected to molecular docking for further refinement. An empirical scoring function was used to evaluate the affinity of the compounds and the target protein. Parts of compounds with high docking scores have been reported to have the related pharmacological activity from the literatures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212027", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 850, "text": "Hit compound 8 was identified as an inhibitor of tankyrases through a combination of substructure searching of the Amgen compound collection based on a minimal binding pharmacophore hypothesis and high-throughput screening. Herein we report the structure- and property-based optimization of compound 8 leading to the identification of more potent and selective tankyrase inhibitors 22 and 49 with improved pharmacokinetic properties in rodents, which are well suited as tool compounds for further in vivo validation studies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24294969", "endSection": "abstract" } ] }, { "body": "How Flaviviridae family of viruses infects vertebrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23312108", "http://www.ncbi.nlm.nih.gov/pubmed/23523057", "http://www.ncbi.nlm.nih.gov/pubmed/23110744", "http://www.ncbi.nlm.nih.gov/pubmed/23738027", "http://www.ncbi.nlm.nih.gov/pubmed/24058903", "http://www.ncbi.nlm.nih.gov/pubmed/22541792", "http://www.ncbi.nlm.nih.gov/pubmed/21413253", "http://www.ncbi.nlm.nih.gov/pubmed/24180115", "http://www.ncbi.nlm.nih.gov/pubmed/24086788", "http://www.ncbi.nlm.nih.gov/pubmed/23030329", "http://www.ncbi.nlm.nih.gov/pubmed/20970724", "http://www.ncbi.nlm.nih.gov/pubmed/23242342", "http://www.ncbi.nlm.nih.gov/pubmed/23594175", "http://www.ncbi.nlm.nih.gov/pubmed/23055570", "http://www.ncbi.nlm.nih.gov/pubmed/22172565", "http://www.ncbi.nlm.nih.gov/pubmed/23194952", "http://www.ncbi.nlm.nih.gov/pubmed/23022371", "http://www.ncbi.nlm.nih.gov/pubmed/23963259", "http://www.ncbi.nlm.nih.gov/pubmed/24284878", "http://www.ncbi.nlm.nih.gov/pubmed/23241081", "http://www.ncbi.nlm.nih.gov/pubmed/22981999", "http://www.ncbi.nlm.nih.gov/pubmed/21216984", "http://www.ncbi.nlm.nih.gov/pubmed/21661323", "http://www.ncbi.nlm.nih.gov/pubmed/23103288", "http://www.ncbi.nlm.nih.gov/pubmed/22925932", "http://www.ncbi.nlm.nih.gov/pubmed/23965926", "http://www.ncbi.nlm.nih.gov/pubmed/22627302", "http://www.ncbi.nlm.nih.gov/pubmed/23017222", "http://www.ncbi.nlm.nih.gov/pubmed/23129759", "http://www.ncbi.nlm.nih.gov/pubmed/22948134", "http://www.ncbi.nlm.nih.gov/pubmed/22226703", "http://www.ncbi.nlm.nih.gov/pubmed/21994755", "http://www.ncbi.nlm.nih.gov/pubmed/22363822", "http://www.ncbi.nlm.nih.gov/pubmed/23099205", "http://www.ncbi.nlm.nih.gov/pubmed/22782946", "http://www.ncbi.nlm.nih.gov/pubmed/22897050" ], "ideal_answer": [ "A wide range of about 500 different viruses is transmitted by arthropods such as ticks, mosquitoes and sandflies. These arboviruses multiply in the arthropod vector, and for each virus there is a natural cycle involving vertebrates (various birds or mammals) and arthropods. The virus enters the arthropod when the latter takes a blood meal from the infected vertebrate, and passes through the gut wall to reach the salivary gland where replication takes place. Once this has occurred, 1\u20132 weeks after ingesting the virus, the arthropod becomes infectious, and can transmit the virus to another vertebrate during a blood meal. Certain arboviruses that infect ticks are also transmitted directly from adult tick to egg (transovarial transmission), so that future generations of ticks are infected without the need for a vertebrate host." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014714", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014712", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018178", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014780", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007239", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016032" ], "type": "summary", "id": "53340ca4d6d3ac6a34000042", "snippets": [ { "offsetInBeginSection": 16, "offsetInEndSection": 390, "text": "(WNV) is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%-40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24284878", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 958, "text": "can be parasitized by Ixodid ticks, which may be infected with tick-borne pathogens, like Borrelia spp., Babesia spp., Anaplasma, Rickettsia/Coxiella, and tick-borne encephalitis virus. The prevalence of ticks on birds varies over years, season, locality and different bird species. The prevalence of ticks on different species depends mainly on the degree of feeding on the ground. In Europe, the Turdus spp., especially the blackbird, Turdus merula, appears to be most important for harboring ticks. Birds can easily cross barriers, like fences, mountains, glaciers, desserts and oceans, which would stop mammals, and they can move much faster than the wingless hosts. Birds can potentially transport tick-borne pathogens by transporting infected ticks, by being infected with tick-borne pathogens and transmit the pathogens to the ticks, and possibly act as hosts for transfer of pathogens between ticks through co-feeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058903", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 811, "text": "The dengue viruses (DENVs) are mosquito-borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a clinical spectrum with severe disease characterized by intravascular volume depletion and hemorrhage. Recent estimates on the burden of DENV infection determined that there are 390 million dengue infections per year, three times the current estimate by the WHO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23963259", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 127, "text": "(WNV), an arbovirus maintained in a bird-mosquito enzootic cycle, can infect other vertebrates including humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738027", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 347, "text": "(WNV), a mosquito-borne flavivirus in the Japanese encephalitis antigenic group, has caused sporadic outbreaks in humans, horses and birds throughout many of the warmer regions of Europe for at least 20 years. Occasional cases of West Nile encephalitis have also been associated with infected blood transfusions and organ donations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594175", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 432, "text": "Dengue is the most important vector-borne disease in many different parts of the world and is expanding into other areas of the globe without hindrance. The morbidity and mortality due to dengue complications are increasing globally at an alarming rate. Although transmission of the dengue virus has been documented in well-characterized areas of Pakistan, its incidence in Khyber Pakhtunkhawa has not been characterized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523057", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 789, "text": " A rising incidence of acute hepatitis C virus (HCV) in HIV-infected MSM has been observed since 2000 in Europe, Australia, USA and Asia. Transmission appears to occur through the permucosal rather than the more usual parenteral route. Although often multifactorial, permucosal risk factors can be classified as behavioural (sexual practices and mucosally administered drugs) and biological (HIV and sexually transmitted infections). This review will describe the epidemiology of HCV infection in this cohort. Current and future treatment strategies will also be outlined in the context of novel, orally bioavailable, directly acting antiviral therapies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242342", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 713, "text": "The genus Flavivirus currently consists of approximately 80 single-strand positive-sense RNA viruses. These replicate in a range of hosts including myriad vertebrate, insect, and tick species. As a consequence of this broad host range, the majority of flaviviruses can be propagated in most vertebrate and insect cell cultures. This ability to infect arthropods and vertebrates usually is essential for maintenance of these viruses in nature. But recently, there has been the discovery of a number of flaviviruses that infect mosquitoes but not vertebrates. It remains largely unknown why certain flaviviruses infect vertebrates and mosquitoes while others infect mosquitoes or vertebrates exclusively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23241081", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 269, "text": "Hepatitis C virus (HCV) transmission among people who inject drugs remains a challenging public health problem. We investigated the risk of HCV transmission by analyzing the direct association of HCV with filters, water to dilute drugs, and water containers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23129759", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 117, "text": " is a mosquito-borne disease caused by four closely related dengue virus (genus Flavivirus)serotypes (DENV-1\u20134)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23110744", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 186, "text": " West Nile viruses are enveloped RNA viruses that belong to genus Flavivirus (family Flaviviridae) and are considered important mosquito-borne viral pathogenic agents worldwide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099205", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 126, "text": " (JEV) is a mosquito-borne pathogenic flavivirus responsible for acute viral encephalitis in humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055570", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 242, "text": "Hepatitis C virus infection (HCV) is not infrequent among haemodialysis patients. Most published reports suggest that patient-to-patient spread, either directly or indirectly, is the most common mode of transmission in renal units", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022371", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 161, "text": "POWV) is a rare tick-borne agent of encephalitis in North America. Historically, confirmed cases occurred mainly in the northeastern United State", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23017222", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 257, "text": "(WNV) is a zoonotic arthropod-borne pathogen with continued geographical expansion in Europe. We present and evaluate data on the temporal, spatial and bird species focus of the WNV surveillance programme in dead wild birds in Great Britain ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22948134", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 567, "text": "YFV) is historically one of the most important viruses to affect human populations. Despite the existence of highly effective vaccines for over 70 years, yellow fever remains a significant and re-emerging cause of morbidity and mortality in endemic and high-risk regions of South America and Africa. The virus may be maintained in sylvatic enzootic/epizootic, transitional and urban epidemic transmission cycles with geographic variation in terms of levels of genetic diversity, the nature of transmission cycles and patterns of outbreak activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981999", "endSection": "abstract" }, { "offsetInBeginSection": 7, "offsetInEndSection": 310, "text": "is a systemic arthropod-borne viral disease of major global public health importance. At least 2.5 billion people who live in areas of the world where dengue occurs are at risk of developing dengue fever (DF) and its severe complications, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22782946", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 153, "text": " is a mosquito-transmitted infection that poses significant global health risks for travelers and individuals living in the tropics and subtropics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541792", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 142, "text": "(WNV) (Flaviviridae: Flavivirus) is transmitted from mosquitoes to birds, but can cause fatal encephalitis in infected humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22226703", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 277, "text": "West Nile virus (WNV) is a member of the genus Flavivirus within the Japanese encephalitis antigenic complex. The enzootic virus cycle involves transmission between avian hosts and ornithophilic mosquitoes, whereas humans and horses are considered dead-end hosts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22172565", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 230, "text": " four major flavivirus clades are transmitted by mosquitoes, ticks, directly between vertebrates or directly between arthropods, respectively, but the molecular determinants of mode of transmission in flaviviruses are unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21216984", "endSection": "abstract" }, { "offsetInBeginSection": 42, "offsetInEndSection": 307, "text": " Tick-borne encephalitis virus (TBEV), one of the most prevalent arboviruses in Europe and in many parts of Asia. Transmission of TBEV to humans usually occurs by bite of an infected tick or rarely by ingestion of unpasteurized milk products of infected livestock. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20970724", "endSection": "abstract" }, { "offsetInBeginSection": 1995, "offsetInEndSection": 2419, "text": "Most alphaviruses and flaviviruses survive in nature by replicating alternately in a vertebrate host and a hematophagous arthropod (mosquitoes or, for some flaviviruses, ticks). Arthropod vectors acquire the viral infection by biting a viremic host, and after an extrinsic incubation period during which the virus replicates in the vector's tissues, they transmit virus through salivary secretions to another vertebrate host", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21413253", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 751, "text": "Western Hemisphere have drawn attention to West Nile virus (WNV) as an international public health problem. Of particular concern has been the ability for the virus to cause outbreaks of disease in highly populated urban centers. Incrimination of Australian mosquito species is an essential component in determining the receptivity of Australia to the introduction and/or establishment of an exotic strain of WNV and can guide potential management strategies. Based on vector competence experiments and ecological studies, we suggest candidate Australian mosquito species that would most likely be involved in urban transmission of WNV, along with consideration of the endemic WNV subtype, Kunjin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23965926", "endSection": "abstract" } ] }, { "body": "What was the aim of the HAMLET clinical trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17400593", "http://www.ncbi.nlm.nih.gov/pubmed/23943217", "http://www.ncbi.nlm.nih.gov/pubmed/19269254", "http://www.ncbi.nlm.nih.gov/pubmed/23868265", "http://www.ncbi.nlm.nih.gov/pubmed/14723030", "http://www.ncbi.nlm.nih.gov/pubmed/17303527", "http://www.ncbi.nlm.nih.gov/pubmed/16965617" ], "ideal_answer": [ "The aim of the HAMLET (Hemicraniectomy After Middle Cerebral Artery Infarction With Life-Threatening Edema Trial) clinical trial was to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction.", "The Hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial (HAMLET) is a newly-conceived randomised multi-centre clinical trial that compares the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction. " ], "type": "summary", "id": "54d776453706e89528000018", "snippets": [ { "offsetInBeginSection": 212, "offsetInEndSection": 531, "text": "METHODS: We assessed clinical outcomes, costs, and cost-effectiveness for the first 3 years in patients who were randomized to surgical decompression or best medical treatment within 48 hours after symptom onset in the Hemicraniectomy After Middle Cerebral Artery Infarction With Life-Threatening Edema Trial (HAMLET). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23943217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Surgical decompression for space-occupying cerebral infarction: outcomes at 3 years in the randomized HAMLET trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868265", "endSection": "title" }, { "offsetInBeginSection": 172, "offsetInEndSection": 413, "text": "METHODS: Patients with space-occupying hemispheric infarction, who were enrolled in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial within 4 days after stroke onset, were followed up at 3 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868265", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 622, "text": "We studied differences in recall of information and in appreciation of the informed consent procedure between representatives included in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET) and representatives of patients participating in the randomised trial of Paracetamol (Acetaminophen) In Stroke (PAIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17400593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965617", "endSection": "title" }, { "offsetInBeginSection": 381, "offsetInEndSection": 577, "text": "This study is designed to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965617", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 717, "text": "The 'Hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial' (HAMLET) is a newly-conceived randomised multi-centre clinical trial that compares the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14723030", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 494, "text": "The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19269254", "endSection": "abstract" } ] }, { "body": "Can we use prodrug amifostine to protect healthy cell during chemotherapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17661222", "http://www.ncbi.nlm.nih.gov/pubmed/16116597", "http://www.ncbi.nlm.nih.gov/pubmed/17602063", "http://www.ncbi.nlm.nih.gov/pubmed/10808697", "http://www.ncbi.nlm.nih.gov/pubmed/10731970", "http://www.ncbi.nlm.nih.gov/pubmed/10553165", "http://www.ncbi.nlm.nih.gov/pubmed/18204866", "http://www.ncbi.nlm.nih.gov/pubmed/8783671", "http://www.ncbi.nlm.nih.gov/pubmed/10963843", "http://www.ncbi.nlm.nih.gov/pubmed/11368288", "http://www.ncbi.nlm.nih.gov/pubmed/16015542", "http://www.ncbi.nlm.nih.gov/pubmed/9099346", "http://www.ncbi.nlm.nih.gov/pubmed/8952658", "http://www.ncbi.nlm.nih.gov/pubmed/12538828", "http://www.ncbi.nlm.nih.gov/pubmed/16267025", "http://www.ncbi.nlm.nih.gov/pubmed/15330181", "http://www.ncbi.nlm.nih.gov/pubmed/9389935", "http://www.ncbi.nlm.nih.gov/pubmed/11336600", "http://www.ncbi.nlm.nih.gov/pubmed/9703784", "http://www.ncbi.nlm.nih.gov/pubmed/19956889", "http://www.ncbi.nlm.nih.gov/pubmed/10348266", "http://www.ncbi.nlm.nih.gov/pubmed/15345895", "http://www.ncbi.nlm.nih.gov/pubmed/8656260", "http://www.ncbi.nlm.nih.gov/pubmed/20021044", "http://www.ncbi.nlm.nih.gov/pubmed/12469164", "http://www.ncbi.nlm.nih.gov/pubmed/15064010", "http://www.ncbi.nlm.nih.gov/pubmed/23626702" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17889382", "o": "N0000022033" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A17889382" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17889382", "o": "AMIFOSTINE/MANNITOL" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A12102802" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1874179", "o": "http://linkedlifedata.com/resource/umls/label/A17985952" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17985952", "o": "N0000022033" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12102802", "o": "4024028" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10488633", "o": "377092" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1251303", "o": "http://linkedlifedata.com/resource/umls/label/A10488633" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1251303", "o": "http://linkedlifedata.com/resource/umls/label/A10488633" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10488633", "o": "Amifostine Injectable Solution" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10414743", "o": "330576" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10414743", "o": "Amifostine 50 MG/ML" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1126264", "o": "http://linkedlifedata.com/resource/umls/label/A10414743" } ], "ideal_answer": [ "Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. However, current radiation doses that can be delivered without causing severe damage to surrounding normal tissues are often insufficient to eradicate a tumor. Recently, a number of agents have been developed to protect normal tissue from the harmful effects of antitumor therapies. The aminothiol amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) has been the subject of extensive research as a prospective protector. While this drug has been approved for use to reduce toxicities associated with cisplatin, several studies also have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. Consequently, higher radiation doses could be used with less than or equal risk to surrounding normal tissues." ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004358", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004999", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020011", "http://www.biosemantics.org/jochem#4217067", "http://www.biosemantics.org/jochem#4277891", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005623", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019610" ], "type": "summary", "id": "534289851eccfd0633000001", "snippets": [ { "offsetInBeginSection": 18, "offsetInEndSection": 451, "text": "CYP), a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23626702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18204866", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Amifostine protects bone marrow from benzene-induced hematotoxicity in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17661222", "endSection": "title" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1538, "text": "Amifostine treatment in benzene-exposed mice significantly improved blood cell counts, and morphological and histopathological signs of hematotoxicity in the bone marrow as well as in the spleen. Moreover, amifostine prevented benzene-induced bone marrow and spleen cell apoptosis and rescinded the inhibition of cell proliferation induced by benzene exposure. Finally, amifostine significantly inhibited the levels of reactive oxidative species and lipid peroxidation induced by benzene exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17661222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Amifostine-antioxidant drug in anticancer therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20021044", "endSection": "title" }, { "offsetInBeginSection": 416, "offsetInEndSection": 725, "text": ". Amifostine alone is inactive chemically, but active metabolite amifostine WR-1065 has been assumed to protect the healthy tissues during antineoplastic therapy by bounding of anticancer drug, causing their detoxification and/or eliminating the free radicals generated during radiation and cytostatic therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20021044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Doxorubicin induces apoptosis in germ line stem cells in the immature rat testis and amifostine cannot protect against this cytotoxicity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16267025", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 86, "text": "Amifostine was developed to protect normal tissues from radiation exposure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16116597", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 119, "text": "(AMF) has been shown to protect some normal tissues from acute effects of radiation therapy +/- chemotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16015542", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 305, "text": "Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15064010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Amifostine inhibits angiogenesis in vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12538828", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Amifostine has shown to selectively protect normal tissues against cytotoxic and mutagenic effects of several anti-neoplastic drugs, such as alkylating agents, organoplatinum compounds, anthracyclines, taxanes, and ionising radiati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12469164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 466, "text": "Amifostine (Ethyoltrade mark, Alza Pharmaceuticals) is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[3- aminopropyl)amino]dihydrogen phosphate. It is a prodrug of free thiol (WR-1065) that may act as a scavenger of free radicals generated in tissues exposed to cytotoxic drugs and binds to reactive metabolites of such drugs. Amifostine was originally developed as a radioprotective agent in a classified nuclear warfare project", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 555, "text": "Preclinical studies demonstrate that amifostine has the potential to selectively protect normal tissues from the harmful effects of radiation without significantly protecting neoplastic tissue. The potential value of such an agent includes reducing treatment-related toxicity and the opportunity for radiation dose escalation in the curative treatment of cancer. An increasing number of human clinical trials have been conducted that define the toxicity profile and efficacy of radioprotection by amifostine when used during fractionated radiation therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8783671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Radioprotective effects of amifostine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10348266", "endSection": "title" } ] }, { "body": "Which is the main difference between Alu and B1 repeats?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "http://www.ncbi.nlm.nih.gov/pubmed/8576966", "http://www.ncbi.nlm.nih.gov/pubmed/17852045", "http://www.ncbi.nlm.nih.gov/pubmed/2412135", "http://www.ncbi.nlm.nih.gov/pubmed/7681065", "http://www.ncbi.nlm.nih.gov/pubmed/1945845", "http://www.ncbi.nlm.nih.gov/pubmed/3221855", "http://www.ncbi.nlm.nih.gov/pubmed/9748291", "http://www.ncbi.nlm.nih.gov/pubmed/1549107", "http://www.ncbi.nlm.nih.gov/pubmed/8036148", "http://www.ncbi.nlm.nih.gov/pubmed/17407136" ], "ideal_answer": [ "B1 is a murine homolog of the human SINE Alu. B1 (Alu-equivalent) is a murine short interspersed element whose amplification probably involved an RNA intermediate. The modern B1 elements are similar to the left Alu monomer, but with a 9 bp deletion and a 29 bp duplication.", "The mouse B1 sequence is congruent to 130 nucleotides long and shows homology with the monomeric units of the dimeric 300-nucleotide primate sequence. " ], "exact_answer": [ "it is the mouse homolog to the left Alu monomer" ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020087" ], "type": "factoid", "id": "56ffd805cf1c32585100000a", "snippets": [ { "offsetInBeginSection": 567, "offsetInEndSection": 718, "text": "The mouse B1 sequence is congruent to 130 nucleotides long and shows homology with the monomeric units of the dimeric 300-nucleotide primate sequence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2412135", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 565, "text": "Here we show that some members of the mouse B1 Alu sequence family encode a small cytoplasmic RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2412135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Alus and B1s are short interspersed repeat elements (SINEs) derived from the 7SL RNA gene. Alus and B1s exist in the cytoplasm as non-coding RNA indicating that they are actively transcribed, but their function, if any, is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "B1 (Alu-equivalent) is a murine short interspersed element whose amplification probably involved an RNA intermediate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1945845", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1221, "text": "The data demonstrate that a limited set of B1 sequences are expressed as processed RNA polymerase III-transcripts of a high degree of structural conservation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1945845", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 145, "text": "B1 is a murine homolog of the human SINE Alu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1549107", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 415, "text": "These RNAs have conserved a secondary structure motif also present in signal recognition particle (SRP) RNA despite substantial sequence divergence, whereas random B1 and Alu sequences have not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7681065", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 178, "text": "The modern B1 elements are similar to the left Alu monomer, but with a 9 bp deletion and a 29 bp duplication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8036148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "A master sequence related to a free left Alu monomer (FLAM) at the origin of the B1 family in rodent genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8036148", "endSection": "title" }, { "offsetInBeginSection": 307, "offsetInEndSection": 572, "text": " The core sequences of these elements contain pol III promoters but must rely on fortuitous downstream oligo(dT) tracts for terminator function. We show that a B1-Alu gene differs markedly from a classical pol III gene (tRNAiMet) in terminator sequence requirements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9748291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Most human Alu and murine B1 repeats are unique.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17407136", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Alu and b1 repeats have been selectively retained in the upstream and intronic regions of genes of specific functional classes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Alu and B1 repeats are mobile elements that originated in an initial duplication of the 7SL RNA gene prior to the primate-rodent split about 80 million years ago and currently account for a substantial fraction of the human and mouse genome, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 778, "text": "we present evidence that Alu and B1 elements have been selectively retained in the upstream and intronic regions of genes belonging to specific functional classes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1388, "text": "Finally, the unexpected finding that Alu and B1 elements show similar biases in their distribution across functional classes, despite having spread independently in their respective genomes, further supports our claim that the extant instances of Alu and B1 elements are the result of positive selection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1036, "text": "Furthermore, the presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric element.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8576966", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 845, "text": "Furthermore, the presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric element.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8576966", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 732, "text": "A statistically reliable slowing down in the evolutionary rates of one of two monomers for the human Alu repeats has been proved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3221855", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 846, "text": "Furthermore, the presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric element.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8576966", "endSection": "abstract" } ] }, { "body": "Is there a relationship between thyroid hormone altered metabolism and coronary artery disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17434631", "http://www.ncbi.nlm.nih.gov/pubmed/9117915", "http://www.ncbi.nlm.nih.gov/pubmed/18497453", "http://www.ncbi.nlm.nih.gov/pubmed/19650571", "http://www.ncbi.nlm.nih.gov/pubmed/16507804", "http://www.ncbi.nlm.nih.gov/pubmed/16649727", "http://www.ncbi.nlm.nih.gov/pubmed/16524858", "http://www.ncbi.nlm.nih.gov/pubmed/23086805", "http://www.ncbi.nlm.nih.gov/pubmed/21745107", "http://www.ncbi.nlm.nih.gov/pubmed/21789282", "http://www.ncbi.nlm.nih.gov/pubmed/17614771", "http://www.ncbi.nlm.nih.gov/pubmed/19609889", "http://www.ncbi.nlm.nih.gov/pubmed/9709915", "http://www.ncbi.nlm.nih.gov/pubmed/732079", "http://www.ncbi.nlm.nih.gov/pubmed/14677810", "http://www.ncbi.nlm.nih.gov/pubmed/22877896", "http://www.ncbi.nlm.nih.gov/pubmed/23470525", "http://www.ncbi.nlm.nih.gov/pubmed/22724581", "http://www.ncbi.nlm.nih.gov/pubmed/17222925" ], "ideal_answer": [ "The major part of the studies and metaanalysis data show that hypothyroidism, both primary and secondary forms, is associated with higher incidence and severity of coronary artery disease." ], "exact_answer": "yes", "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023921", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013959", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003331", "http://www.disease-ontology.org/api/metadata/DOID:3393" ], "type": "yesno", "id": "531d1279b166e2b806000042", "snippets": [ { "offsetInBeginSection": 1516, "offsetInEndSection": 1747, "text": "The results showed that higher levels of TSH within the reference range were independently associated with the presence of CAD only among subjects less than or equal to 65 years old, suggesting age might influence the relationship.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23470525", "endSection": "abstract" }, { "offsetInBeginSection": 1594, "offsetInEndSection": 1829, "text": "FT3 levels within the normal range were inversely correlated with the presence and severity of CAD. Moreover, lower FT3 concentrations were correlated with the Gensini score and independently predicted the presence and severity of CAD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22877896", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1221, "text": "High TSH within the reference range was associated with increased risk of coronary death in women (P(trend) 0\u00b7005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0\u00b750-1\u00b74 mU/l. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22724581", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1186, "text": " Prevalence of CHD was more common in hypothyroid and moderate SCH patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745107", "endSection": "abstract" }, { "offsetInBeginSection": 1657, "offsetInEndSection": 2003, "text": "The angiographic results were as follows: significant coronary disease (SH 28.1% vs. non-SH 43.8%; p=0.087); three-vessel disease (9.4% vs. 9.9%; p=0.919); two-vessel disease (12.5% vs. 13.4%; p=0.892); single-vessel disease (6.3% vs. 29.5%; p=0.051); minimal lesions (9.4% vs. 10.9%; p=0.794); and no coronary disease (62.4% vs, 45.3%; p=0.064).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19650571", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 962, "text": "Lower fT3 levels were predictive of both single-vessel (p = 0.012) and multivessel (p = 0.009) CAD. Through a multivariate logistic regression analysis, fT3 was still linked to the presence of CAD (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.34-0.68, p < 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19609889", "endSection": "abstract" }, { "offsetInBeginSection": 1556, "offsetInEndSection": 1766, "text": "Our study showed that FT(4) levels were associated with the presence and the severity of CAD. Also, this study suggests that elevated serum FT(4) levels even within normal range could be a risk factor for CAD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18497453", "endSection": "abstract" }, { "offsetInBeginSection": 2114, "offsetInEndSection": 2263, "text": "The present meta-analysis indicates that sub-clinical hypothyroidism is associated with both, a significant risk of CHD at baseline and at follow-up.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17434631", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1398, "text": "The incidence of multi-vessel disease was higher in patients with high TSH level (p=0.026). TSH level showed a significant correlation with age (r=0.109, p=0.044) and Gensini's score (r=0.117, p=0.045). The multivariate analysis revealed that age (OR 2.39, p=0.001), diabetes (OR 3.74, p=0.001), creatinine (OR 2.06, p=0.008), and smoking (OR 1.85, p=0.045) were independent predictors for significant coronary artery disease, but TSH level did not predict coronary artery stenosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17222925", "endSection": "abstract" }, { "offsetInBeginSection": 2580, "offsetInEndSection": 2784, "text": "These data in patients referred for coronary angiography suggest that variation of thyroid function within the statistical normal range may influence the presence and severity of coronary atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14677810", "endSection": "abstract" } ] }, { "body": "What is the frequency of mutations induced spontaneously through Ethylnitrosourea (ENU) mutagenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18504270", "http://www.ncbi.nlm.nih.gov/pubmed/12410959", "http://www.ncbi.nlm.nih.gov/pubmed/15450411", "http://www.ncbi.nlm.nih.gov/pubmed/3863118", "http://www.ncbi.nlm.nih.gov/pubmed/10700191", "http://www.ncbi.nlm.nih.gov/pubmed/509687", "http://www.ncbi.nlm.nih.gov/pubmed/10886029" ], "ideal_answer": [ "Theoretical considerations and empirical analysis suggest that the per-base mutation frequency for a fractionated-dose treatment protocol is on the order of 1 sequence change per 10(5) bp." ], "exact_answer": [ "1/100000" ], "concepts": [ "http://www.biosemantics.org/jochem#4249285", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017354", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016296", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059645", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005038", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "factoid", "id": "533ba85ffd9a95ea0d000008", "snippets": [ { "offsetInBeginSection": 820, "offsetInEndSection": 991, "text": "The mutation frequency increased linearly with MNU or ENU concentration (0.01--2.0 mM); mean values were 2800 and 840 mutants per 10(6) clonable cells per mM, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/509687", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 900, "text": "The mutation frequency induced by a 400 mg/kg dosage of ethylnitrosourea is 12 times the maximal mutation frequency achievable with a single exposure to x-rays and 36 times that reported for procarbazine, the most effective chemical mutagen previously known for mouse stem-cell spermatogonia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3863118", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 694, "text": "Specific locus tests designed to detect recessive mutations showed that ENU is the most efficient mutagen in mouse with an approximate mutation rate of 1 in 1,000 gametes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10700191", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1153, "text": "Theoretical considerations and empirical analysis suggest that the per-base mutation frequency for a fractionated-dose treatment protocol is on the order of 1 sequence change per 10(5) bp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10886029", "endSection": "abstract" }, { "offsetInBeginSection": 1285, "offsetInEndSection": 1504, "text": "Unlike spontaneous chromosome damage, spontaneous mutant frequencies did not differ significantly among homozygous, heterozygous, and wild-type mice (3.2 x 10(-5), 3.1 x 10(-5), and 3.1 x 10(-5), respectively; P > 0.05)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15450411", "endSection": "abstract" }, { "offsetInBeginSection": 1667, "offsetInEndSection": 1831, "text": "The ENU-induced mutation frequency in Blmtm3Brd homozygous, heterozygous, and wild mice were 54 x 10(-5), 35 x 10(-5), and 25 x 10(-5) mutants/plaques, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15450411", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1130, "text": "mutation frequencies per nucleotide based on mutant spectra from this study and published literature. We found this frequency in control spleen to be similar for lacI (3.8 +/- 0.7 x 10(-8)) and PhiX174 (3.1 +/- 1.2 x 10(-8)) at 6 weeks of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18504270", "endSection": "abstract" } ] }, { "body": "What is the molecular pathogenesis of Spinal Muscular Atrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18572081", "http://www.ncbi.nlm.nih.gov/pubmed/24112438", "http://www.ncbi.nlm.nih.gov/pubmed/23740936" ], "ideal_answer": [ "Spinal muscular atrophy is an autosomal recessive neurodegenerative disease characterised by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalised weakness. It is caused by homozygous disruption of the survival motor neuron 1 (SMN1) gene by deletion, conversion, or mutation, resulting in downregulated biogenesis of uridine-rich small nuclear RNAs (U snRNAs), which are major components of the splicing machinery." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050530", "http://www.disease-ontology.org/api/metadata/DOID:0060160", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014897", "http://www.disease-ontology.org/api/metadata/DOID:0050529", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009134", "http://www.disease-ontology.org/api/metadata/DOID:12377", "http://www.disease-ontology.org/api/metadata/DOID:12376", "http://www.disease-ontology.org/api/metadata/DOID:318", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055533" ], "type": "summary", "id": "52f124a12059c6d71c000006", "snippets": [ { "offsetInBeginSection": 1031, "offsetInEndSection": 1144, "text": "A mouse model of spinal muscular atrophy, in which the number of Gems is decreased, shows fewer subsets U snRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24112438", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 514, "text": "TDP-43 associates with nuclear bodies including Gemini of coiled bodies (GEMs). GEMs contribute to the biogenesis of uridine-rich small nuclear RNA (U snRNA), a component of splicing machinery. The number of GEMs and a subset of U snRNAs decrease in spinal muscular atrophy, a lower motor neuron disease,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23740936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Spinal muscular atrophy is an autosomal recessive neurodegenerative disease characterised by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalised weakness. It is caused by homozygous disruption of the survival motor neuron 1 (SMN1) gene by deletion, conversion, or mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18572081", "endSection": "abstract" } ] }, { "body": "Which drugs affect insulin resistance in obesity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17482151", "http://www.ncbi.nlm.nih.gov/pubmed/9374813", "http://www.ncbi.nlm.nih.gov/pubmed/19236237", "http://www.ncbi.nlm.nih.gov/pubmed/21276223", "http://www.ncbi.nlm.nih.gov/pubmed/23619228", "http://www.ncbi.nlm.nih.gov/pubmed/17437648", "http://www.ncbi.nlm.nih.gov/pubmed/21270237", "http://www.ncbi.nlm.nih.gov/pubmed/22292446", "http://www.ncbi.nlm.nih.gov/pubmed/22247785", "http://www.ncbi.nlm.nih.gov/pubmed/23702383", "http://www.ncbi.nlm.nih.gov/pubmed/24090942", "http://www.ncbi.nlm.nih.gov/pubmed/22412882", "http://www.ncbi.nlm.nih.gov/pubmed/22983924", "http://www.ncbi.nlm.nih.gov/pubmed/23735317", "http://www.ncbi.nlm.nih.gov/pubmed/21440024", "http://www.ncbi.nlm.nih.gov/pubmed/22435392", "http://www.ncbi.nlm.nih.gov/pubmed/23144896", "http://www.ncbi.nlm.nih.gov/pubmed/18925326", "http://www.ncbi.nlm.nih.gov/pubmed/22275759", "http://www.ncbi.nlm.nih.gov/pubmed/24072084", "http://www.ncbi.nlm.nih.gov/pubmed/23176795", "http://www.ncbi.nlm.nih.gov/pubmed/23808738", "http://www.ncbi.nlm.nih.gov/pubmed/22878697", "http://www.ncbi.nlm.nih.gov/pubmed/23820981" ], "ideal_answer": [ "Enistein treatment could help reduce insulin resistance\nACE inhibitor drugs may improve insulin resistance" ], "exact_answer": [ [ "Enistein" ], [ "ACE inhibitors" ] ], "concepts": [ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007333", "http://www.disease-ontology.org/api/metadata/DOID:14221", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009765", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061385", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007328", "http://www.disease-ontology.org/api/metadata/DOID:9970", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019440", "http://www.uniprot.org/uniprot/INS_CAIMO" ], "type": "list", "id": "52e7b7cb98d023950500001c", "snippets": [ { "offsetInBeginSection": 1481, "offsetInEndSection": 1696, "text": "enistein treatment could help reduce insulin resistance through the amelioration of OVX-induced metabolic dysfunction, and the GSEA approach may be useful in proposing putative targets related to insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176795", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1475, "text": "he positive effects of ACE inhibitor drugs, particularly on hypertriglyceridemia and insulin resistance, might bring them forth as first-line drugs in the treatment of obese and hypertensive children. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072084", "endSection": "abstract" } ] }, { "body": "Elaborate on the link between conserved noncoding elements (CNEs) and fractality.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26899868", "http://www.ncbi.nlm.nih.gov/pubmed/24787386" ], "ideal_answer": [ "Well-developed fractality is revealed for the chromosomal distribution of different classes of CNEs in the human genome by employing the scaling of block entropy and box-counting. This is characteristic of elements that are either extremely conserved between species or are of ancient origin, i.e. conserved between distant organisms across evolution. There are also power-law-like distributions, i.e. linearity in double logarithmic scale, in the inter-CNE distances, a feature which is connected with fractality and self-similarity." ], "type": "summary", "id": "587f57f692a5b8ad44000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Fractality and entropic scaling in the chromosomal distribution of conserved noncoding elements in the human genome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26899868", "endSection": "title" }, { "offsetInBeginSection": 211, "offsetInEndSection": 696, "text": "We explored the chromosomal distribution of different classes of CNEs in the human genome. We employed two methodologies: the scaling of block entropy and box-counting, with the aim to assess fractal characteristics of different CNE datasets. Both approaches converged to the conclusion that well-developed fractality is characteristic of elements that are either extremely conserved between species or are of ancient origin, i.e. conserved between distant organisms across evolution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26899868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Conserved noncoding elements follow power-law-like distributions in several genomes as a result of genome dynamics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24787386", "endSection": "title" }, { "offsetInBeginSection": 480, "offsetInEndSection": 666, "text": "We find widespread power-law-like distributions, i.e. linearity in double logarithmic scale, in the inter-CNE distances, a feature which is connected with fractality and self-similarity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24787386", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 667, "text": "We find widespread power-law-like distributions, i.e. linearity in double logarithmic scale, in the inter-CNE distances, a feature which is connected with fractality and self-similarity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24787386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Conserved noncoding elements follow power-law-like distributions in several genomes as a result of genome dynamics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24787386", "endSection": "title" } ] }, { "body": "Which is the primary protein component of Lewy bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23180276", "http://www.ncbi.nlm.nih.gov/pubmed/11814405", "http://www.ncbi.nlm.nih.gov/pubmed/10722726", "http://www.ncbi.nlm.nih.gov/pubmed/20551689", "http://www.ncbi.nlm.nih.gov/pubmed/24252509", "http://www.ncbi.nlm.nih.gov/pubmed/16343531", "http://www.ncbi.nlm.nih.gov/pubmed/23965852", "http://www.ncbi.nlm.nih.gov/pubmed/10327208", "http://www.ncbi.nlm.nih.gov/pubmed/18510319", "http://www.ncbi.nlm.nih.gov/pubmed/22843682", "http://www.ncbi.nlm.nih.gov/pubmed/24058647", "http://www.ncbi.nlm.nih.gov/pubmed/26667592", "http://www.ncbi.nlm.nih.gov/pubmed/23344955", "http://www.ncbi.nlm.nih.gov/pubmed/18607609", "http://www.ncbi.nlm.nih.gov/pubmed/10764738", "http://www.ncbi.nlm.nih.gov/pubmed/11440819", "http://www.ncbi.nlm.nih.gov/pubmed/23557146", "http://www.ncbi.nlm.nih.gov/pubmed/22516611", "http://www.ncbi.nlm.nih.gov/pubmed/9726379", "http://www.ncbi.nlm.nih.gov/pubmed/16452621", "http://www.ncbi.nlm.nih.gov/pubmed/24392030", "http://www.ncbi.nlm.nih.gov/pubmed/26502720", "http://www.ncbi.nlm.nih.gov/pubmed/10825478", "http://www.ncbi.nlm.nih.gov/pubmed/11207422", "http://www.ncbi.nlm.nih.gov/pubmed/17899395", "http://www.ncbi.nlm.nih.gov/pubmed/11900526", "http://www.ncbi.nlm.nih.gov/pubmed/19475665", "http://www.ncbi.nlm.nih.gov/pubmed/18508479", "http://www.ncbi.nlm.nih.gov/pubmed/10762166", "http://www.ncbi.nlm.nih.gov/pubmed/20617407", "http://www.ncbi.nlm.nih.gov/pubmed/26401513", "http://www.ncbi.nlm.nih.gov/pubmed/11085897", "http://www.ncbi.nlm.nih.gov/pubmed/23796501", "http://www.ncbi.nlm.nih.gov/pubmed/12122208", "http://www.ncbi.nlm.nih.gov/pubmed/14502650", "http://www.ncbi.nlm.nih.gov/pubmed/16319716", "http://www.ncbi.nlm.nih.gov/pubmed/24586691", "http://www.ncbi.nlm.nih.gov/pubmed/9600990", "http://www.ncbi.nlm.nih.gov/pubmed/22483285", "http://www.ncbi.nlm.nih.gov/pubmed/26161848", "http://www.ncbi.nlm.nih.gov/pubmed/25846226", "http://www.ncbi.nlm.nih.gov/pubmed/11816795", "http://www.ncbi.nlm.nih.gov/pubmed/12541013", "http://www.ncbi.nlm.nih.gov/pubmed/12722831", "http://www.ncbi.nlm.nih.gov/pubmed/20890676" ], "ideal_answer": [ "The primary protein component of Lewy bodies are fibrils composed of alpha-synuclein." ], "exact_answer": [ "alpha-synuclein", "\u03b1-synuclein", "\u03b1Syn" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016631", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051844" ], "type": "factoid", "id": "58a2e5f760087bc10a000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Aggregation of \u03b1-synuclein (\u03b1Syn), the primary protein component in Lewy body inclusions of patients with Parkinson's disease, arises when the normally soluble intrinsically disordered protein converts to amyloid fibrils. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058647", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 500, "text": "The primary structural component of Lewy bodies are fibrils composed primarily of alpha-synuclein, a highly conserved 140 amino acid protein that is predominantly expressed in neurons and which may play a role in synaptic plasticity and neurotransmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22483285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Fibrillar \u03b1-synuclein (AS) is the major component of Lewy bodies, the pathological hallmark of Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Alpha-synuclein (alphaS) is the primary component of Lewy bodies, the pathological hallmark of Parkinson's Disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19475665", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 827, "text": "For alpha-synuclein, the major protein component of Lewy bodies associated with Parkinson's disease, we have used a combination of ssNMR and biochemical data to identify the key region for self-aggregation of the protein as residues 77-82 (VAQKTV). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18510319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The protein alpha-synuclein (AS) is the primary fibrillar component of Lewy bodies, the pathological hallmark of Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17899395", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 276, "text": "Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10327208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Alpha-synuclein forms the major component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9726379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "\u00e1-Synuclein is the major protein component of Lewy bodies--the pathological hallmark of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20617407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "alpha-Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11085897", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1089, "text": "The segregation of alpha-synuclein to Lewy body peripheral domain is consistent with the hypothesis that alpha-synuclein is continually deposited onto Lewy bodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11085897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Identification of protein interfaces between \u03b1-synuclein, the principal component of Lewy bodies in Parkinson disease, and the molecular chaperones human Hsc70 and the yeast Ssa1p", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22843682", "endSection": "title" }, { "offsetInBeginSection": 374, "offsetInEndSection": 634, "text": "Whereas approximately 550 proteins were identified in the LB-enriched sample by mass spectrometry, quantitative comparison with the control sample revealed that approximately 40 proteins were co-enriched with alpha-synuclein, the major component in Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18508479", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 1085, "text": "This apparent conflict in protein levels might have arisen from examining Lewy body disease cases with coexisting Alzheimer-type pathologies.To assess whether ATP13A2 levels in Lewy body disease are modified by Alzheimer-type \u03b2-amyloid deposition, we evaluated cases of pure PD and pure dementia with Lewy bodies (DLB) for changes in ATP13A2, \u03b1-synuclein and \u03b2-amyloid protein levels in cortical regions with and without Lewy bodies.In all Lewy body disease cases, we identified decreased ATP13A2 protein levels that correlated with increases in both \u03b1-synuclein and \u03b2-amyloid", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252509", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1444, "text": "Partial colocalization was observed between ATP13A2 and \u03b1-synuclein in Lewy bodies, whereas ATP13A2 did not colocalize with pathological \u03b2-amyloid deposition.Our data show that patients with Lewy body diseases have an overall deficit in ATP13A2 protein levels, with the remaining protein being more insoluble and partially redistributing towards Lewy bodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24252509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Identification of protein interfaces between \u03b1-synuclein, the principal component of Lewy bodies in Parkinson disease, and the molecular chaperones human Hsc70 and the yeast Ssa1p.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22843682", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Human \u03b1-synuclein is a small-sized, natively unfolded protein that in fibrillar form is the primary component of Lewy bodies, the pathological hallmark of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23557146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Parkinson's disease is the most common neurodegenerative movement disorder. \u03b1-Synuclein is a small synaptic protein that has been linked to familial Parkinson's disease (PD) and is also the primary component of Lewy bodies, the hallmark neuropathology found in the brain of sporadic and familial PD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20890676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The protein alpha-synuclein (AS) is the primary fibrillar component of Lewy bodies, the pathological hallmark of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17899395", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "\u03b1-Synuclein is an abundant presynaptic protein and a primary component of Lewy bodies in Parkinson disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23344955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The natively disordered protein alpha-synuclein is the primary component of Lewy bodies, the cellular hallmark of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16343531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Common cellular and molecular mechanisms including protein aggregation and inclusion body formation are involved in many neurodegenerative diseases. \u03b1-Synuclein is a major component of Lewy bodies in Parkinson's disease (PD) as well as in glial cytoplasmic inclusions in multiple system atrophy (MSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23965852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Alpha-synuclein (\u03b1-Syn) is the principal protein component of Lewy bodies, a pathological hallmark of Parkinson's disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23796501", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Lewy bodies and coarse Lewy neurites are the pathological hallmarks of degenerating neurons in the brains of patients suffering from Parkinson's disease (PD). Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10327208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "Lewy bodies and coarse Lewy neurites are the pathological hallmarks of degenerating neurons in the brains of patients suffering from Parkinson's disease (PD). Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites. This study demonstrates for the first time that extensive and thin alpha-synuclein-immunoreactive inclusions are present in the axonal processes of neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10327208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "\u00e1-Synuclein is the major protein component of Lewy bodies--the pathological hallmark of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). Its accumulation into intracellular aggregates is implicated in the process of Lewy body formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20617407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9726379", "endSection": "title" }, { "offsetInBeginSection": 199, "offsetInEndSection": 330, "text": "Lewy bodies comprise of aggregated intracellular vesicles and proteins and \u03b1-synuclein is reported to be a major protein component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26667592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10764738", "endSection": "title" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1384, "text": "These findings indicate that alpha-synuclein forms the major filamentous component of Lewy bodies and Lewy neurites..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9600990", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1405, "text": "The protein alpha-synuclein appears to be an important structural component of Lewy bodies, an observation spurred by the discovery of point mutations in the alpha-synuclein gene linked to rare cases of autosomal dominant PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11816795", "endSection": "abstract" } ] }, { "body": "Are microtubules marked by glutamylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26227334", "http://www.ncbi.nlm.nih.gov/pubmed/19700636", "http://www.ncbi.nlm.nih.gov/pubmed/23973077", "http://www.ncbi.nlm.nih.gov/pubmed/26000474", "http://www.ncbi.nlm.nih.gov/pubmed/25959773", "http://www.ncbi.nlm.nih.gov/pubmed/25030760" ], "ideal_answer": [ "Yes, glutamylation is the most prevalent tubulin posttranslational modification and marks stable microtubules." ], "exact_answer": "yes", "type": "yesno", "id": "58aa0a62396a458e50000007", "snippets": [ { "offsetInBeginSection": 1220, "offsetInEndSection": 1385, "text": "Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26227334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Glutamylation, the most prevalent tubulin posttranslational modification, marks stable microtubules and regulates recruitment and activity of microtubule- interacting proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Enzymes of the tubulin tyrosine ligase-like (TTLL) family posttranslationally modify and thereby mark microtubules by glutamylation, generating specific recognition sites for microtubule-interacting proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26000474", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 942, "text": " PTMs of the cytoskeleton, including phosphorylation, glycosylation, ubiquitination, detyrosination/tyrosination, (poly)glutamylation and (poly)glycylation, acetylation, sumoylation, and palmitoylation, will be addressed in this chapter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25030760", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 408, "text": "The tubulin posttranslational modifications: acetylation, detyrosination, polyglutamylation, and polyglycylation play important roles in microtubule functions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23973077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "In most eukaryotic cells, tubulin is subjected to posttranslational glutamylation, a conserved modification of unclear function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19700636", "endSection": "abstract" } ] }, { "body": "What is known about the Kub5-Hera/RPRD1B interactome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26819409" ], "ideal_answer": [ "Ku70-binding protein 5 (Kub5)-Hera (K-H)/RPRD1B maintains genetic integrity by concomitantly minimizing persistent R-loops and promoting repair of DNA double strand breaks (DSBs). Thus, the Kub5-Hera/RPRD1B interactome plays a novel role in preserving genetic stability by regulating DNA mismatch repair." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053843" ], "type": "summary", "id": "5881f0f1713cbdfd3d000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The Kub5-Hera/RPRD1B interactome: a novel role in preserving genetic stability by regulating DNA mismatch repair", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26819409", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Ku70-binding protein 5 (Kub5)-Hera (K-H)/RPRD1B maintains genetic integrity by concomitantly minimizing persistent R-loops and promoting repair of DNA double strand breaks (DSBs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26819409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The Kub5-Hera/RPRD1B interactome: a novel role in preserving genetic stability by regulating DNA mismatch repair.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26819409", "endSection": "title" } ] }, { "body": "Willis-Ekbom disease is also known as?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24605270", "http://www.ncbi.nlm.nih.gov/pubmed/25510187", "http://www.ncbi.nlm.nih.gov/pubmed/26329430", "http://www.ncbi.nlm.nih.gov/pubmed/25301914", "http://www.ncbi.nlm.nih.gov/pubmed/26725086", "http://www.ncbi.nlm.nih.gov/pubmed/22678064", "http://www.ncbi.nlm.nih.gov/pubmed/25113274", "http://www.ncbi.nlm.nih.gov/pubmed/26298794", "http://www.ncbi.nlm.nih.gov/pubmed/26077324", "http://www.ncbi.nlm.nih.gov/pubmed/26545868", "http://www.ncbi.nlm.nih.gov/pubmed/24812538", "http://www.ncbi.nlm.nih.gov/pubmed/23963470", "http://www.ncbi.nlm.nih.gov/pubmed/24293752", "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "http://www.ncbi.nlm.nih.gov/pubmed/27292821", "http://www.ncbi.nlm.nih.gov/pubmed/26298776", "http://www.ncbi.nlm.nih.gov/pubmed/23859128", "http://www.ncbi.nlm.nih.gov/pubmed/25093484", "http://www.ncbi.nlm.nih.gov/pubmed/26329447", "http://www.ncbi.nlm.nih.gov/pubmed/26329446", "http://www.ncbi.nlm.nih.gov/pubmed/24892899", "http://www.ncbi.nlm.nih.gov/pubmed/23397977", "http://www.ncbi.nlm.nih.gov/pubmed/25201131", "http://www.ncbi.nlm.nih.gov/pubmed/24992148", "http://www.ncbi.nlm.nih.gov/pubmed/25230997", "http://www.ncbi.nlm.nih.gov/pubmed/24001490", "http://www.ncbi.nlm.nih.gov/pubmed/26429756", "http://www.ncbi.nlm.nih.gov/pubmed/24157095", "http://www.ncbi.nlm.nih.gov/pubmed/15165536", "http://www.ncbi.nlm.nih.gov/pubmed/26874840", "http://www.ncbi.nlm.nih.gov/pubmed/24246378", "http://www.ncbi.nlm.nih.gov/pubmed/27481386", "http://www.ncbi.nlm.nih.gov/pubmed/27662970" ], "ideal_answer": [ "Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common movement disorder characterized by an uncontrollable urge to move because of uncomfortable, sometimes painful sensations in the legs with a diurnal variation and a release with movement." ], "exact_answer": [ "Restless legs syndrome" ], "type": "factoid", "id": "5891f9e549702f2e01000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Defining the phenotype of restless legs syndrome/Willis-Ekbom disease (RLS/WED): a clinical and polysomnographic study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26725086", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Clinical features variability between familial and sporadic restless legs syndrome/Willis-Ekbom disease (RLS/WED) has been previously reported. With this retrospective cohort study, we aimed to determine the clinical and polysomnographic characteristics of 400 RLS/WED patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26725086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "\"Emplotted Narratives\" and Structured \"Behavioral Observations\" Supporting the Diagnosis of Willis-Ekbom Disease/Restless Legs Syndrome in Children with Neurodevelopmental Conditions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292821", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "BACKGROUND: Willis-Ekbom disease/restless legs syndrome (WED/RLS) seems to be a frequent cause of intractable chronic insomnia (ICI) but is under-recognized in children/adolescents with neurodevelopmental conditions (NDCs), as many patients do not have the ability to express the underlying \"urge-to-move\". ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common movement disorder characterised by an uncontrollable urge to move because of uncomfortable, sometimes painful sensations in the legs with a diurnal variation and a release with movement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "OBJECTIVE: In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED).METHODS: The AGES-Reykjavik cohort (born 1907-1935) has been followed since 1967.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "BACKGROUND: Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensory-motor neurological disorder with a circadian component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22678064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "There is no consensus about mechanisms underlying restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26429756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common sensorimotor disorder that can generally be effectively managed in the primary care clinic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26077324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder for which the exact pathophysiology remains unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25201131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensorimotor disorder that can result in considerable sleep disruption", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 448, "text": "The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED).The AGES-Reykjavik cohort (born 1907-1935) has been followed since 1967", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Restless leg syndrome (RLS), also known as Willis-Ekbom disease, is a condition that includes sensations such as crawling, tingling, or aching in the limbs and creates an urge to move", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24992148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND: Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "OBJECTIVES: Both restless legs syndrome ([RLS], also known as Willis-Ekbom Disease [WED]) and depression are common during pregnancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24812538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensory-motor neurological disorder with a circadian component. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22678064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "OBJECTIVE: In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "BACKGROUND: Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "BACKGROUND: The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Psychological distress in patients with restless legs syndrome (Willis-Ekbom disease): a population-based door-to-door survey in rural Ecuador.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510187", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Restless leg syndrome/Willis-Ekbom disease has brain iron deficiency that produces excessive dopamine and known genetic risks, some of which contribute to the brain iron deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26329430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common sensorimotor disorder that can generally be effectively managed in the primary care clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26077324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensorimotor disorder that can result in considerable sleep disruption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25093484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED).The AGES-Reykjavik cohort (born 1907-1935) has been followed since 1967.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is characterised by abnormal sensations in the legs as well as dysaesthesia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27662970", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the pathogenic mechanisms of RLS are not entirely understood, it is becoming increasingly evident that many diseases such as RLS can be attributed to an epistasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "OBJECTIVE: Restless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is a sensorimotor-related sleep disorder. Little is known of the effect of RLS/WED on motor function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25113274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "OBJECTIVE: Restless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is a sensorimotor-related sleep disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25113274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Upper limb function is normal in patients with restless legs syndrome (Willis-Ekbom Disease).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25113274", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 461, "text": "BACKGROUND: The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24246378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder for which the exact pathophysiology remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25201131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common movement disorder characterised by an uncontrollable urge to move because of uncomfortable, sometimes painful sensations in the legs with a diurnal variation and a release with movement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The relationship among restless legs syndrome (Willis-Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23963470", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Willis-Ekbom Disease or Restless Legs Syndrome?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26298794", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Living with Restless Legs Syndrome/Willis-Ekbom Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26329446", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Restless Legs Syndrome/Willis-Ekbom Disease Morbidity: Burden, Quality of Life, Cardiovascular Aspects, and Sleep.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26329447", "endSection": "title" } ] }, { "body": "List two most common symptoms of Aagenaes syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19498211", "http://www.ncbi.nlm.nih.gov/pubmed/23626552", "http://www.ncbi.nlm.nih.gov/pubmed/10968776", "http://www.ncbi.nlm.nih.gov/pubmed/25039919", "http://www.ncbi.nlm.nih.gov/pubmed/9350821", "http://www.ncbi.nlm.nih.gov/pubmed/24086631", "http://www.ncbi.nlm.nih.gov/pubmed/16635916", "http://www.ncbi.nlm.nih.gov/pubmed/27614462", "http://www.ncbi.nlm.nih.gov/pubmed/25317502", "http://www.ncbi.nlm.nih.gov/pubmed/8278949", "http://www.ncbi.nlm.nih.gov/pubmed/12712065", "http://www.ncbi.nlm.nih.gov/pubmed/20170991", "http://www.ncbi.nlm.nih.gov/pubmed/11446017" ], "ideal_answer": [ "Aagenaes syndrome, also called lymphoedema cholestasis syndrome 1, is characterized by neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age and severe chronic lymphoedema, mainly affecting the lower extremities." ], "exact_answer": [ [ "intrahepatic cholestasis" ], [ "lymphoedema" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:6691", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816" ], "type": "list", "id": "5895f9cf78275d0c4a000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Aagenaes syndrome, also called lymphoedema cholestasis syndrome 1 (LSC1), is characterized by neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age and severe chronic lymphoedema, mainly affecting the lower extremities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27614462", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 319, "text": "In this study, 17 out of 20 Norweigian adult patients with lymphedema cholestasis syndrome 1 (LCS1)/Aagenaes syndrome were examined. The patients exhibited lymphedema and sporadic cholestasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25317502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "BACKGROUND: Lymphedema-cholestasis syndrome (LCS; Aagenaes syndrome) is a rare autosomal recessive disorder, characterized by 1) neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age, and 2) severe chronic lymphedema, mainly lower limb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086631", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 325, "text": "The disease was thought to be caused by a congenital cholestatic syndrome associated with intermittent oedema in childhood, resembling the rare Aagenaes syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23626552", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Do patients with lymphoedema cholestasis syndrome 1/Aagenaes syndrome need dietary counselling outside cholestatic episodes?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20170991", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "BACKGROUND & AIMS: Patients with lymphoedema cholestasis syndrome 1/Aagenaes Syndrome need a fat reduced diet when cholestatic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20170991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Aagenaes syndrome, also called Lymphedema Cholestasis Syndrome (LSC 1), is a form of idiopathic familial intrahepatic cholestasis associated with lymphedema of the lower extremities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19498211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Aagenaes syndrome, also called Lymphedema Cholestasis Syndrome (LSC 1), is a form of idiopathic familial intrahepatic cholestasis associated with lymphedema of the lower extremities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19498211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Parent-child transmission of infantile cholestasis with lymphoedema (Aagenaes syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9350821", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Mapping of the locus for cholestasis-lymphedema syndrome (Aagenaes syndrome) to a 6.6-cM interval on chromosome 15q.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10968776", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Lymphedema-cholestasis syndrome (LCS, Aagenaes syndrome) is the only known form of hereditary lymphedema associated with cholestasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12712065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "OBJECTIVE: To investigate the prognosis of liver disease in Aagenaes syndrome (lymphoedema cholestasis syndrome 1 (LCS1)), which is an autosomal recessive inherited syndrome consisting of neonatal cholestasis with intermittent cholestatic episodes in childhood into adulthood and development of lymphoedema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16635916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "BACKGROUND: Lymphedema-cholestasis syndrome (LCS; Aagenaes syndrome) is a rare autosomal recessive disorder, characterized by 1) neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age, and 2) severe chronic lymphedema, mainly lower limb. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24086631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "[Aagenaes syndrome--lymphedema and intrahepatic cholestasis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11446017", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Parent-child transmission of infantile cholestasis with lymphoedema (Aagenaes syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9350821", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Hereditary lymphedema, characteristics, and variations in 17 adult patients with lymphedema cholestasis syndrome 1/Aagenaes syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25317502", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Lymphedema-cholestasis syndrome (LCS, Aagenaes syndrome) is the only known form of hereditary lymphedema associated with cholestasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12712065", "endSection": "abstract" } ] }, { "body": "Which are the side effects during tacrine administration in patients with Alzheimer's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9808364", "http://www.ncbi.nlm.nih.gov/pubmed/22034058", "http://www.ncbi.nlm.nih.gov/pubmed/9226744", "http://www.ncbi.nlm.nih.gov/pubmed/9408186", "http://www.ncbi.nlm.nih.gov/pubmed/17883890", "http://www.ncbi.nlm.nih.gov/pubmed/8237620", "http://www.ncbi.nlm.nih.gov/pubmed/7737527", "http://www.ncbi.nlm.nih.gov/pubmed/19270633", "http://www.ncbi.nlm.nih.gov/pubmed/7579023", "http://www.ncbi.nlm.nih.gov/pubmed/25858345", "http://www.ncbi.nlm.nih.gov/pubmed/19370562", "http://www.ncbi.nlm.nih.gov/pubmed/8312036", "http://www.ncbi.nlm.nih.gov/pubmed/9209244", "http://www.ncbi.nlm.nih.gov/pubmed/2107926", "http://www.ncbi.nlm.nih.gov/pubmed/8119309", "http://www.ncbi.nlm.nih.gov/pubmed/22192081", "http://www.ncbi.nlm.nih.gov/pubmed/9050085", "http://www.ncbi.nlm.nih.gov/pubmed/7510447", "http://www.ncbi.nlm.nih.gov/pubmed/17636619", "http://www.ncbi.nlm.nih.gov/pubmed/10796507", "http://www.ncbi.nlm.nih.gov/pubmed/1406817", "http://www.ncbi.nlm.nih.gov/pubmed/7868848", "http://www.ncbi.nlm.nih.gov/pubmed/10325444", "http://www.ncbi.nlm.nih.gov/pubmed/7919566", "http://www.ncbi.nlm.nih.gov/pubmed/12939598", "http://www.ncbi.nlm.nih.gov/pubmed/8139084" ], "ideal_answer": [ "The side effects during tacrine administration in patients with Alzheimer's Disease are:\r\n1) Hepatotoxicity\r\n2) Gastrointestinal (diarrhea, anorexia, dyspepsia, abdominal pain, nausea, vomiting)\r\n3) Mitochondrial impairement" ], "exact_answer": [ [ "Hepatotoxicity" ], [ "Gastrointestinal" ], [ "diarrhea" ], [ "anorexia" ], [ "dyspepsia" ], [ "abdominal pain" ], [ "nausea" ], [ "vomiting" ], [ "anorexia" ], [ "Mitochondrial impairement" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4274748", "http://www.biosemantics.org/jochem#4274748", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013619" ], "type": "list", "id": "58a2fac960087bc10a000009", "snippets": [ { "offsetInBeginSection": 366, "offsetInEndSection": 537, "text": "Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25858345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Tacrine and its analogues impair mitochondrial function and bioenergetics: a lipidomic analysis in rat brain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22192081", "endSection": "title" }, { "offsetInBeginSection": 127, "offsetInEndSection": 235, "text": "However, its low therapeutic efficiency and a high incidence of side effects have limited its clinical use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22192081", "endSection": "abstract" }, { "offsetInBeginSection": 1839, "offsetInEndSection": 2098, "text": "Tacrine induced significant perturbations in the mitochondrial PL profile, which were detected by means of changes in the relative abundance of phosphatidylcholine (PC), PE, phosphatidylinositol (PI) and CL and by the presence of oxidized phosphatidylserines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22192081", "endSection": "abstract" }, { "offsetInBeginSection": 2446, "offsetInEndSection": 2595, "text": "These results indicate that tacrine and its analogues impair mitochondrial function and bioenergetics, thus compromising the activity of brain cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22192081", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 561, "text": "Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19370562", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 617, "text": "The antidementives are well tolerated and undesired effects are rare; except hepatotoxicity of tacrine and gastrointestinal side effects of donepezil, rivastigmine, galantamin and tacrine that result from acetylcholinesterase inhibition. Nausea, diarrhea, vomiting, and weight loss are the most common side effects of the acetylcholinesterase inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270633", "endSection": "abstract" }, { "offsetInBeginSection": 2984, "offsetInEndSection": 3048, "text": "Raised serum liver enzymes was the major reason for withdrawal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17636619", "endSection": "abstract" }, { "offsetInBeginSection": 3208, "offsetInEndSection": 3486, "text": "Gastrointestinal side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other major cause of adverse events and for withdrawal, and the odds ratio for withdrawal was also significantly different from one in favour of the control group (OR 3.8; 95%CI 2.8-5.1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17636619", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1231, "text": "To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17636619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "In Alzheimer's disease, cognition now responds to several drugs. Anticholinesterases target the acetylcholine deficit. In mild-to-moderate Alzheimer's disease, they all provide significant benefit versus placebo on the Alzheimer's Disease Assessment ScheduleCognitive Section (ADAS-Cog), Side effects, in 5% to 15% of cases, include nausea, vomiting, diarrhea, anorexia, and dizziness. Tacrine, the leading anticholinesterase, caused frequent hepatic enzyme elevation and was withdrawn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22034058", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 637, "text": "This 12-week randomised, double-blind, placebo-controlled study was undertaken to evaluate the ability of silymarin to antagonise or prevent the hepatotoxic effects of tacrine and to analyse its action on tacrine efficacy and tolerability.METHODS: Outpatients suffering from mild-to-moderate dementia of the Alzheimer type were randomly assigned to two treatment groups: tacrine + silymarin and tacrine + placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10325444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Hepatotoxic effects of tacrine administration in patients with Alzheimers disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8139084", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8139084", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Tremulous jaw movements produced by acute tacrine administration: possible relation to parkinsonian side effects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9050085", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Administration of tacrine (THA) for the treatment of Alzheimer's disease results in a reversible hepatotoxicity in 30-50% of patients, as indicated by an increase in transaminase levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9808364", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 637, "text": "Tacrine, the first drug marketed for Alzheimer's disease (AD), induces an elevation of serum liver transaminase prohibiting an effective dosage in many patients. This 12-week randomised, double-blind, placebo-controlled study was undertaken to evaluate the ability of silymarin to antagonise or prevent the hepatotoxic effects of tacrine and to analyse its action on tacrine efficacy and tolerability.METHODS: Outpatients suffering from mild-to-moderate dementia of the Alzheimer type were randomly assigned to two treatment groups: tacrine + silymarin and tacrine + placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10325444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 637, "text": "BACKGROUND: Silymarin is a well-known hepatoprotective agent. Tacrine, the first drug marketed for Alzheimer's disease (AD), induces an elevation of serum liver transaminase prohibiting an effective dosage in many patients. This 12-week randomised, double-blind, placebo-controlled study was undertaken to evaluate the ability of silymarin to antagonise or prevent the hepatotoxic effects of tacrine and to analyse its action on tacrine efficacy and tolerability.METHODS: Outpatients suffering from mild-to-moderate dementia of the Alzheimer type were randomly assigned to two treatment groups: tacrine + silymarin and tacrine + placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10325444", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 763, "text": "Tacrine, the first drug marketed for Alzheimer's disease (AD), induces an elevation of serum liver transaminase prohibiting an effective dosage in many patients. This 12-week randomised, double-blind, placebo-controlled study was undertaken to evaluate the ability of silymarin to antagonise or prevent the hepatotoxic effects of tacrine and to analyse its action on tacrine efficacy and tolerability.METHODS: Outpatients suffering from mild-to-moderate dementia of the Alzheimer type were randomly assigned to two treatment groups: tacrine + silymarin and tacrine + placebo. The study was double-blind for silymarin and open for tacrine and was conducted in 22 French neurology and geriatric centres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10325444", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 223, "text": "Tacrine, the first drug marketed for Alzheimer's disease (AD), induces an elevation of serum liver transaminase prohibiting an effective dosage in many patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10325444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8139084", "endSection": "title" } ] }, { "body": "Is synapsin a phosphoprotein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26425441", "http://www.ncbi.nlm.nih.gov/pubmed/26400944", "http://www.ncbi.nlm.nih.gov/pubmed/25843720", "http://www.ncbi.nlm.nih.gov/pubmed/25576091", "http://www.ncbi.nlm.nih.gov/pubmed/26538647", "http://www.ncbi.nlm.nih.gov/pubmed/25972175", "http://www.ncbi.nlm.nih.gov/pubmed/25967550", "http://www.ncbi.nlm.nih.gov/pubmed/26670182" ], "ideal_answer": [ "Yes, synapsin is an evolutionarily conserved presynaptic phosphoprotein." ], "exact_answer": "yes", "type": "yesno", "id": "58a8962338c171fb5b000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Synapsin is an evolutionarily conserved presynaptic phosphoprotein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26670182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Synapsins as a family of presynaptic terminal phosphoprotein participates in neuronal development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25576091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Synapsin III (SynIII) is a phosphoprotein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25843720", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 325, "text": "The neuronal phosphoprotein synapsin III", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25967550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Synapsin II is a member of the neuronal phosphoprotein family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26425441", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 480, "text": "phosphoprotein synapsin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26538647", "endSection": "abstract" } ] }, { "body": "Is Thalidomide currently a marketed drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22695124", "http://www.ncbi.nlm.nih.gov/pubmed/11604049", "http://www.ncbi.nlm.nih.gov/pubmed/26652728", "http://www.ncbi.nlm.nih.gov/pubmed/10512502", "http://www.ncbi.nlm.nih.gov/pubmed/9987477", "http://www.ncbi.nlm.nih.gov/pubmed/22650376", "http://www.ncbi.nlm.nih.gov/pubmed/11558112", "http://www.ncbi.nlm.nih.gov/pubmed/24931258", "http://www.ncbi.nlm.nih.gov/pubmed/11899395", "http://www.ncbi.nlm.nih.gov/pubmed/11091366", "http://www.ncbi.nlm.nih.gov/pubmed/8592478", "http://www.ncbi.nlm.nih.gov/pubmed/25573527" ], "ideal_answer": [ "Several mechanisms for the teratogenic action of thalidomide are currently under review, but this mode of action of the drug still remains unclear and we review evidence-based hypotheses for the teratogenicity of thalidomide. Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered. THE USE OF A DRUG WITH A TEMPORARY MARKETING AUTHORISATION: Thalidomide is currently available in France for nominative or cohort use with a temporary marketing authorisation (TMA). Examples of the basis for such regulation are drawn from historical situations (thalidomide, benoxaprofen) as well as currently marketed drugs (arylpropionic acids, disopyramide, indacrinone). In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects. The US Food and Drug Administration (FDA) has approved Thalomid (thalidomide) capsules for the acute treatment of the cutaneous manifestations of moderate to severe ENL. The revival of thalidomide began shortly after the drug was withdrawn from the market because of its teratogenic properties.", "Thalidomide is currently used to treat multiple Myeloma, possibly POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes ) syndrome and IBS" ], "exact_answer": "yes", "type": "yesno", "id": "58a0d87a78275d0c4a000053", "snippets": [ { "offsetInBeginSection": 210, "offsetInEndSection": 336, "text": "In this retrospective study, pharmacy claims were analyzed for those patients with a diagnosis of MM who received thalidomide,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26652728", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 730, "text": "The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25573527", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 188, "text": "Thalidomide could relieve clinical symptoms and intestinal mucosal lesions effectively in children with refractory inflammatory bowel disease (IBD) from the pre-clinical study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Thalidomide is now available as an investigational drug in the USA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8592478", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 1046, "text": "The STEPStrade mark (System for Thalidomide Education and Prescribing Safety) Program has been developed by Celgene, the commercial manufacturer of thalidomide, to ensure compliance with prescription and usage protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11091366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 24, "text": "New uses of thalidomide.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8592478", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Thalidomide is an anti-angiogenesis agent that currently is being evaluated in the treatment of various types of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11899395", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1160, "text": "The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650376", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 836, "text": "Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11558112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22695124", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 560, "text": "Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9987477", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 337, "text": "In 1998, FDA approved the marketing of thalidomide (Thalomid, Celgene). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10512502", "endSection": "abstract" }, { "offsetInBeginSection": 1625, "offsetInEndSection": 1826, "text": "In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11604049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "BACKGROUND: The use of thalidomide during the 1950s resulted in teratogenic effects in thousands of infants. Although thalidomide is currently approved for the treatment of a complication of leprosy, it is commercially available to treat other diseases through a controlled distribution system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11091366", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1162, "text": "The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650376", "endSection": "abstract" } ] }, { "body": "Which enzymes synthesize catecholamines in adrenal glands?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7602797", "http://www.ncbi.nlm.nih.gov/pubmed/12573802", "http://www.ncbi.nlm.nih.gov/pubmed/2427537", "http://www.ncbi.nlm.nih.gov/pubmed/23469", "http://www.ncbi.nlm.nih.gov/pubmed/26187454", "http://www.ncbi.nlm.nih.gov/pubmed/8105763", "http://www.ncbi.nlm.nih.gov/pubmed/15135223", "http://www.ncbi.nlm.nih.gov/pubmed/3777139", "http://www.ncbi.nlm.nih.gov/pubmed/9061614", "http://www.ncbi.nlm.nih.gov/pubmed/9578504", "http://www.ncbi.nlm.nih.gov/pubmed/20634527", "http://www.ncbi.nlm.nih.gov/pubmed/10423683", "http://www.ncbi.nlm.nih.gov/pubmed/24032", "http://www.ncbi.nlm.nih.gov/pubmed/23508458", "http://www.ncbi.nlm.nih.gov/pubmed/25903953", "http://www.ncbi.nlm.nih.gov/pubmed/23903565", "http://www.ncbi.nlm.nih.gov/pubmed/15094322", "http://www.ncbi.nlm.nih.gov/pubmed/6119179", "http://www.ncbi.nlm.nih.gov/pubmed/22473696", "http://www.ncbi.nlm.nih.gov/pubmed/6139026", "http://www.ncbi.nlm.nih.gov/pubmed/1969734", "http://www.ncbi.nlm.nih.gov/pubmed/15345906", "http://www.ncbi.nlm.nih.gov/pubmed/22934574" ], "ideal_answer": [ "The enzymes that synthesize catecholamines in adrenal glands are:\n1) Tyrosine Hydroxylase (TH)\n2) Aromatic L-amino acid decarboxylase (AAAD)\n3) Dopamine \u03b2-hydroxylase (DBH)\n4) Phenylethanolamine N-methyltransferase (PNMT)" ], "exact_answer": [ [ "Tyrosine Hydroxylase", "TH" ], [ "Aromatic L-amino acid decarboxylase", "AAAD", "AADC", "DDC" ], [ "Dopamine \u03b2-hydroxylase", "DBH" ], [ "Phenylethanolamine N-methyltransferase", "PNMT" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000302", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002395", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000311", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000313" ], "type": "list", "id": "589c215778275d0c4a00003c", "snippets": [ { "offsetInBeginSection": 318, "offsetInEndSection": 699, "text": "We analyzed the mRNA levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AAAD), dopamine-\u03b2-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands of 18 pigs with chronic systolic non-ischaemic HF (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 sham-operated controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25903953", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 728, "text": "This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-\u00df-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23903565", "endSection": "abstract" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1731, "text": "In the adrenal medulla, despite the absence of morphological changes, immunohistochemistry for tyrosine hydroxylase, dopamine \u03b2-hydroxylase and phenyl-ethanolamine-N-methyltransferase demonstrated an increased immunopositivity for these cathecolamine-synthesizing enzymes after intense exercise. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473696", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 1152, "text": "Using isolated adrenal medulla we observed no difference in basal catecholamine secretion percentile between obese and lean animals. However, the percentile of catecholamine secretion stimulated by high K+ concentration was lower in the obese group. There was a decrease in the tyrosine hydroxylase enzyme expression (57.3%, P<0.004) in adrenal glands of obese mice. Interestingly, the expression of dopamine beta-hydroxylase was also reduced (47.0%, P<0.005). Phenylethanolamine N-methyltransferase expression was not affected. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15094322", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 534, "text": "Differential housing (single vs. group) and social defeat of rats is known to alter the activity of catecholamine-synthesizing enzymes in the medulla. The present studies examined the effect of 70 days of triad (3 rats per large cage) and individual housing of male rats on adrenal mRNA levels of tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) and on TH protein levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15345906", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 651, "text": "As a first step toward understanding the molecular mechanisms by which catecholamine synthesis is controlled in the tumor, we measured the levels of mRNA coding for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines in 6 pheochromocytomas and 2 normal adrenal glands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7602797", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1064, "text": "We also examined the gene expression of the messengers of other catecholamine synthesizing enzymes, dopamine beta-hydroxylase (DBH) and aromatic 1-amino acid decarboxylase (AADC) in pheochromocytomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7602797", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1334, "text": "These findings indicate that catecholamine overproduction in pheochromocytomas is mediated by the overexpression of genes coding for catecholamines synthesizing enzymes, TH, DBH, and AADC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7602797", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 208, "text": "he present study investigated the cellular localization of 3 catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20634527", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 834, "text": "tyrosine hydroxylase (TH) the rate limiting catecholamine biosynthetic enzyme and also of dopamine beta-hydroxylase (DBH)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15135223", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 483, "text": "tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) in sympathetic ganglia and adrenals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6119179", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 726, "text": "This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-\u00df-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23903565", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 649, "text": "As a first step toward understanding the molecular mechanisms by which catecholamine synthesis is controlled in the tumor, we measured the levels of mRNA coding for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines in 6 pheochromocytomas and 2 normal adrenal glands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7602797", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 698, "text": "We analyzed the mRNA levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AAAD), dopamine-\u03b2-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands of 18 pigs with chronic systolic non-ischaemic HF (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 sham-operated controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25903953", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 727, "text": "This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-\u00df-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23903565", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 482, "text": "We used immunocytochemistry to study the ontogeny of leu-enkephalin and the catecholamine-synthesizing enzymes dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase in adjacent sections of 14 fetal rhesus and 31 fetal human adrenal glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2427537", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 650, "text": "As a first step toward understanding the molecular mechanisms by which catecholamine synthesis is controlled in the tumor, we measured the levels of mRNA coding for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines in 6 pheochromocytomas and 2 normal adrenal glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7602797", "endSection": "abstract" } ] }, { "body": "How many cysteines have alpha-defensins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24386139", "http://www.ncbi.nlm.nih.gov/pubmed/24557891", "http://www.ncbi.nlm.nih.gov/pubmed/25970658", "http://www.ncbi.nlm.nih.gov/pubmed/22168415" ], "ideal_answer": [ "Alpha defensins contain six cysteines, which form three well defined disulfide bridges under oxidizing conditions." ], "exact_answer": [ "Alpha defensins contain six conserved cysteines" ], "type": "factoid", "id": "58a9c532396a458e50000002", "snippets": [ { "offsetInBeginSection": 178, "offsetInEndSection": 293, "text": "Alpha defensins contain six cysteines, which form three well defined disulfide bridges under oxidizing conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25970658", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 636, "text": "All three kinds of defensins have six conserved cysteines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24557891", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 522, "text": " There are six cysteines in the sequence of mature CFBD peptide, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24386139", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 179, "text": "They typically contain six conserved cysteines whose three intramolecular disulfides stabilize a largely \u03b2-sheet structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22168415", "endSection": "abstract" } ] }, { "body": "Could BRCA gene test used for breast and ovarian cancer risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20221693", "http://www.ncbi.nlm.nih.gov/pubmed/17394399", "http://www.ncbi.nlm.nih.gov/pubmed/21913181", "http://www.ncbi.nlm.nih.gov/pubmed/17901820", "http://www.ncbi.nlm.nih.gov/pubmed/26271414", "http://www.ncbi.nlm.nih.gov/pubmed/27004793", "http://www.ncbi.nlm.nih.gov/pubmed/19841329", "http://www.ncbi.nlm.nih.gov/pubmed/20711702", "http://www.ncbi.nlm.nih.gov/pubmed/24366376", "http://www.ncbi.nlm.nih.gov/pubmed/26848859", "http://www.ncbi.nlm.nih.gov/pubmed/23165859", "http://www.ncbi.nlm.nih.gov/pubmed/17109443", "http://www.ncbi.nlm.nih.gov/pubmed/16174860", "http://www.ncbi.nlm.nih.gov/pubmed/24731853", "http://www.ncbi.nlm.nih.gov/pubmed/23635950", "http://www.ncbi.nlm.nih.gov/pubmed/12632763", "http://www.ncbi.nlm.nih.gov/pubmed/18854964", "http://www.ncbi.nlm.nih.gov/pubmed/23539753", "http://www.ncbi.nlm.nih.gov/pubmed/20233464", "http://www.ncbi.nlm.nih.gov/pubmed/27513691", "http://www.ncbi.nlm.nih.gov/pubmed/18932252", "http://www.ncbi.nlm.nih.gov/pubmed/17079882", "http://www.ncbi.nlm.nih.gov/pubmed/20878485", "http://www.ncbi.nlm.nih.gov/pubmed/25863477", "http://www.ncbi.nlm.nih.gov/pubmed/26047126", "http://www.ncbi.nlm.nih.gov/pubmed/25849179", "http://www.ncbi.nlm.nih.gov/pubmed/27276934", "http://www.ncbi.nlm.nih.gov/pubmed/25838294", "http://www.ncbi.nlm.nih.gov/pubmed/26852130", "http://www.ncbi.nlm.nih.gov/pubmed/19996028", "http://www.ncbi.nlm.nih.gov/pubmed/26402875", "http://www.ncbi.nlm.nih.gov/pubmed/16144895", "http://www.ncbi.nlm.nih.gov/pubmed/22381151", "http://www.ncbi.nlm.nih.gov/pubmed/24366442", "http://www.ncbi.nlm.nih.gov/pubmed/27306910", "http://www.ncbi.nlm.nih.gov/pubmed/27403072", "http://www.ncbi.nlm.nih.gov/pubmed/23091540", "http://www.ncbi.nlm.nih.gov/pubmed/26922077", "http://www.ncbi.nlm.nih.gov/pubmed/19273395", "http://www.ncbi.nlm.nih.gov/pubmed/17579227", "http://www.ncbi.nlm.nih.gov/pubmed/21637635", "http://www.ncbi.nlm.nih.gov/pubmed/10464631", "http://www.ncbi.nlm.nih.gov/pubmed/26691940", "http://www.ncbi.nlm.nih.gov/pubmed/22982855", "http://www.ncbi.nlm.nih.gov/pubmed/24950059", "http://www.ncbi.nlm.nih.gov/pubmed/22866093", "http://www.ncbi.nlm.nih.gov/pubmed/19479365", "http://www.ncbi.nlm.nih.gov/pubmed/24065545", "http://www.ncbi.nlm.nih.gov/pubmed/27376595", "http://www.ncbi.nlm.nih.gov/pubmed/25497409", "http://www.ncbi.nlm.nih.gov/pubmed/16783967", "http://www.ncbi.nlm.nih.gov/pubmed/26411315", "http://www.ncbi.nlm.nih.gov/pubmed/18515440", "http://www.ncbi.nlm.nih.gov/pubmed/12708108", "http://www.ncbi.nlm.nih.gov/pubmed/11368874", "http://www.ncbi.nlm.nih.gov/pubmed/24698998", "http://www.ncbi.nlm.nih.gov/pubmed/23638402", "http://www.ncbi.nlm.nih.gov/pubmed/25236687", "http://www.ncbi.nlm.nih.gov/pubmed/9150154", "http://www.ncbi.nlm.nih.gov/pubmed/23528734", "http://www.ncbi.nlm.nih.gov/pubmed/23165893", "http://www.ncbi.nlm.nih.gov/pubmed/22438049", "http://www.ncbi.nlm.nih.gov/pubmed/16492929", "http://www.ncbi.nlm.nih.gov/pubmed/27928164", "http://www.ncbi.nlm.nih.gov/pubmed/22684231", "http://www.ncbi.nlm.nih.gov/pubmed/24161304", "http://www.ncbi.nlm.nih.gov/pubmed/25948675" ], "ideal_answer": [ "Yes, BRCA gene test could be used for breast and ovarian cancer risk, as female BRCA1 and BRCA2 mutations are significantly associated with risk of developing breast and ovarian cancers." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:5683", "http://www.disease-ontology.org/api/metadata/DOID:2394", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019313", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024682" ], "type": "yesno", "id": "58a6bce660087bc10a000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25838294", "endSection": "title" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1645, "text": "The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26402875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26402875", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Maximising survival: the main concern of women with hereditary breast and ovarian cancer who undergo genetic testing for BRCA1/2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853", "endSection": "title" }, { "offsetInBeginSection": 8, "offsetInEndSection": 342, "text": " Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term. This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1310, "text": "The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 \u00d7 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 \u00d7 10(-3)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24698998", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 193, "text": "Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23528734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065545", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065545", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 276, "text": "Until 2006, she supervised a diagnostic unit for BRCA gene testing at the Interdisciplinary Center for Hereditary Breast Cancer (Max Delbr\u00fcck Center, Berlin, Germany). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24161304", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 218, "text": "Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23638402", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 162, "text": "Women who carry a BRCA1 or BRCA2 gene mutation face a risk of developing breast or ovarian cancer at an earlier age than women without such a mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982855", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 447, "text": "In 2006, participants were recruited from Web sites for women with breast cancer or BRCA gene mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982855", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 252, "text": "About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26852130", "endSection": "abstract" }, { "offsetInBeginSection": 1662, "offsetInEndSection": 1765, "text": "Suggestion of an association between BRCA2 c.7806-2A>G and risk of breast cancer in males has emerged. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26852130", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 221, "text": "The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27403072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23528734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16783967", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1370, "text": "She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913181", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 652, "text": "We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20221693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26271414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "[Detection and occurrence of BRCA 1 gene mutation in patients with carcinoma of the breast and ovary].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 391, "text": "We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.PATIENTS WITH BREAST CANCER WHO HAD AT LEAST ONE OF THE FOLLOWING RISK FACTORS WERE ENROLLED: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23091540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 757, "text": "Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24366442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC).From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23165859", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1471, "text": "Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913181", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 1136, "text": "The USPSTF also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations, including intensive cancer screening, medications, and risk-reducing surgery.This recommendation applies to asymptomatic women who have not been diagnosed with BRCA-related cancer.The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24366376", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1478, "text": "If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21637635", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 1070, "text": "A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.Mutations of BRCA1 or BRCA2.Breast and ovarian cancer risks.Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25849179", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 450, "text": "This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.METHODS: A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 431, "text": "This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27376595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26848859", "endSection": "abstract" }, { "offsetInBeginSection": 2081, "offsetInEndSection": 2225, "text": "Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27004793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Mutations in BRCA genes elevate risk for breast and ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23635950", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 2030, "text": "Observational studies of prophylactic surgeries report reduced risks for breast and ovarian cancer in mutation carriers.No data describe the range of risk associated with BRCA mutations, genetic heterogeneity, and moderating factors; studies conducted in highly selected populations contain biases; and information on adverse effects is incomplete.A primary care approach to screening for inherited breast and ovarian cancer susceptibility has not been evaluated, and evidence is lacking to determine benefits and harms for the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16144895", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 936, "text": "We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20221693", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 1370, "text": "Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer. One asymptomatic person--carrier of BRCA 1 gene mutation--was identified in this study. She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26271414", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1505, "text": "Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21913181", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 971, "text": "Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12708108", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1621, "text": "However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25863477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26047126", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 279, "text": "Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19996028", "endSection": "abstract" }, { "offsetInBeginSection": 2358, "offsetInEndSection": 2491, "text": "Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16492929", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 991, "text": "Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17109443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 413, "text": "Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25236687", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 678, "text": "Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17901820", "endSection": "abstract" }, { "offsetInBeginSection": 1757, "offsetInEndSection": 1863, "text": "BRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27306910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539753", "endSection": "title" }, { "offsetInBeginSection": 1978, "offsetInEndSection": 2185, "text": "Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17109443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Genetic testing for breast cancer susceptibility became a reality after two cancer predisposition genes, BRCA1 and BRCA2, were identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10464631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19996028", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 690, "text": "We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539753", "endSection": "abstract" } ] }, { "body": "What is Desomorphine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24650492", "http://www.ncbi.nlm.nih.gov/pubmed/23388531", "http://www.ncbi.nlm.nih.gov/pubmed/23244560", "http://www.ncbi.nlm.nih.gov/pubmed/26282512", "http://www.ncbi.nlm.nih.gov/pubmed/25710781", "http://www.ncbi.nlm.nih.gov/pubmed/27372715", "http://www.ncbi.nlm.nih.gov/pubmed/25236385", "http://www.ncbi.nlm.nih.gov/pubmed/22468632", "http://www.ncbi.nlm.nih.gov/pubmed/27348169" ], "ideal_answer": [ "Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil", "Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin", "Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil", "\"Krokodil\" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin.", "Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin", "Desomorphine is an opioid drug which is often synthsised using a combination of readily available ingredients and is often available on the \"street\" as a cheaper alternative to heroin." ], "concepts": [ "http://www.biosemantics.org/jochem#4011470", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4011470" ], "type": "summary", "id": "58a5d7ef60087bc10a000026", "snippets": [ { "offsetInBeginSection": 214, "offsetInEndSection": 300, "text": "Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25710781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27372715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "\"Krokodil\" is the street name for the semi-synthetic opioid derivative desomorphine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27372715", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 429, "text": "ince Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine (\"Krokodile\") replacing each other on the black market. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27348169", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 472, "text": "ous increase in the number of addicted individuals since then. The psychoactive core agent of Krokodil is desomorphine, an opioid-analogon that can be manufactured by boiling tablets containing codeine and other ingredients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23244560", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 461, "text": "The core agent of \"Krokodil\" is desomorphine, an opioid-analogue that can be easily and cheaply manufactured by oneself.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22468632", "endSection": "abstract" } ] }, { "body": "Which two drugs are included in the Harvoni pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27480956", "http://www.ncbi.nlm.nih.gov/pubmed/25837989", "http://www.ncbi.nlm.nih.gov/pubmed/25516691", "http://www.ncbi.nlm.nih.gov/pubmed/25859119", "http://www.ncbi.nlm.nih.gov/pubmed/26357632", "http://www.ncbi.nlm.nih.gov/pubmed/26327920", "http://www.ncbi.nlm.nih.gov/pubmed/26312999", "http://www.ncbi.nlm.nih.gov/pubmed/27606041", "http://www.ncbi.nlm.nih.gov/pubmed/25937625", "http://www.ncbi.nlm.nih.gov/pubmed/25850880", "http://www.ncbi.nlm.nih.gov/pubmed/25987834", "http://www.ncbi.nlm.nih.gov/pubmed/27193156", "http://www.ncbi.nlm.nih.gov/pubmed/26788571", "http://www.ncbi.nlm.nih.gov/pubmed/27276081" ], "ideal_answer": [ "Harvoni contains 400 mg sofosbuvir and 90 mg ledipasvir. It used for treatment of hepatitis C virus infection." ], "exact_answer": [ [ "sofosbuvir" ], [ "ledipasvir" ] ], "type": "list", "id": "5896deff78275d0c4a000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27276081", "endSection": "title" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1435, "text": "The developed method was applied to the analysis of the two drugs after a single oral administration of Harvoni 400/90 mg film-coated tablets containing 400 mg sofosbuvir and 90 mg ledipasvir to four healthy volunteers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27480956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "After the introductions of sofosbuvir (Sovaldi) and ledipasvir plus sofosbuvir (Harvoni) for the treatment of hepatitis C, employers have become very sensitive to new, and especially unforeseen, factors that significantly raise healthcare costs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27606041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The single-tablet regimen of the hepatitis C virus (HCV) NS5A inhibitor ledipasvir and the HCV NS5B polymerase inhibitor sofosbuvir (ledipasvir/sofosbuvir; Harvoni(\u00ae)) was recently approved in the US and the EU. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25837989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Ledipasvir/Sofosbuvir (harvoni): improving options for hepatitis C virus infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25859119", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Ledipasvir/sofosbuvir (Harvoni): improving options for hepatitis C virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25859119", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 936, "text": "Also reviewed were recent practice guidelines on the management of HCV infections, prescribing information on all HCV drugs approved by the US Food and Drug Administration, and health technology assessments of Sovaldi\u00ae and Harvoni(TM) (sofosbuvir/ledipasvir).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25850880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Ledipasvir/Sofosbuvir (harvoni): improving options for hepatitis C virus infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25859119", "endSection": "title" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1104, "text": "This review will summarize the data regarding these interferon-free regimens, including Gilead's Harvoni (sofosbuvir/ledipasvir), AbbVie's Viekira Pak (paritaprevir/ritonavir/ombitasvir with dasabuvir), and Janssen's Olysio (simeprevir) with sofosbuvir.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26327920", "endSection": "abstract" } ] }, { "body": "What is the result of Mff overexpression in mitochondria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26446846", "http://www.ncbi.nlm.nih.gov/pubmed/21149567", "http://www.ncbi.nlm.nih.gov/pubmed/24167709" ], "ideal_answer": [ "The Drp1 receptor Mff is a major regulator of mitochondrial fission, and its overexpression results in increased fission." ], "type": "summary", "id": "58a874c338c171fb5b000003", "snippets": [ { "offsetInBeginSection": 337, "offsetInEndSection": 459, "text": "The Drp1 receptor Mff is a major regulator of mitochondrial fission, and its overexpression results in increased fission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26446846", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1088, "text": "Overexpression of MFF also increases the interaction between DLP1 and Pex11p\u03b2, which knockdown of MFF, but not Fis1, abolishes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24167709", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 621, "text": "whereas Mff overexpression stimulated mitochondrial recruitment of Drp1 accompanied by mitochondrial fission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149567", "endSection": "abstract" } ] }, { "body": "Has Glucose-6-phosphate dehydrogenase (G6PD) deficiency an X-linked inheritance?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24865682", "http://www.ncbi.nlm.nih.gov/pubmed/15297240", "http://www.ncbi.nlm.nih.gov/pubmed/25189226", "http://www.ncbi.nlm.nih.gov/pubmed/12169625", "http://www.ncbi.nlm.nih.gov/pubmed/3377761", "http://www.ncbi.nlm.nih.gov/pubmed/2912069", "http://www.ncbi.nlm.nih.gov/pubmed/25771467", "http://www.ncbi.nlm.nih.gov/pubmed/7801429", "http://www.ncbi.nlm.nih.gov/pubmed/25116429", "http://www.ncbi.nlm.nih.gov/pubmed/26827633", "http://www.ncbi.nlm.nih.gov/pubmed/15226563", "http://www.ncbi.nlm.nih.gov/pubmed/24460025", "http://www.ncbi.nlm.nih.gov/pubmed/23429543", "http://www.ncbi.nlm.nih.gov/pubmed/1147889", "http://www.ncbi.nlm.nih.gov/pubmed/26139767", "http://www.ncbi.nlm.nih.gov/pubmed/1634454", "http://www.ncbi.nlm.nih.gov/pubmed/9290617", "http://www.ncbi.nlm.nih.gov/pubmed/21164249", "http://www.ncbi.nlm.nih.gov/pubmed/26275698", "http://www.ncbi.nlm.nih.gov/pubmed/26226515", "http://www.ncbi.nlm.nih.gov/pubmed/11271380", "http://www.ncbi.nlm.nih.gov/pubmed/24943486", "http://www.ncbi.nlm.nih.gov/pubmed/10698963", "http://www.ncbi.nlm.nih.gov/pubmed/1188317", "http://www.ncbi.nlm.nih.gov/pubmed/6350992", "http://www.ncbi.nlm.nih.gov/pubmed/24551713", "http://www.ncbi.nlm.nih.gov/pubmed/3810219", "http://www.ncbi.nlm.nih.gov/pubmed/17355169", "http://www.ncbi.nlm.nih.gov/pubmed/23152723", "http://www.ncbi.nlm.nih.gov/pubmed/1554817", "http://www.ncbi.nlm.nih.gov/pubmed/1953691", "http://www.ncbi.nlm.nih.gov/pubmed/1225290", "http://www.ncbi.nlm.nih.gov/pubmed/631693", "http://www.ncbi.nlm.nih.gov/pubmed/24958328", "http://www.ncbi.nlm.nih.gov/pubmed/23834949", "http://www.ncbi.nlm.nih.gov/pubmed/1296572", "http://www.ncbi.nlm.nih.gov/pubmed/10645652" ], "ideal_answer": [ "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005952", "http://www.uniprot.org/uniprot/G6PD_HELPY", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005955", "http://www.disease-ontology.org/api/metadata/DOID:2862", "http://www.uniprot.org/uniprot/G6PD_HAEIN", "http://www.uniprot.org/uniprot/G6PD_MACRO", "http://www.uniprot.org/uniprot/G6PD_TAKRU", "http://www.uniprot.org/uniprot/G6PD_CRIGR", "http://www.uniprot.org/uniprot/G6PD_GLUOX", "http://www.uniprot.org/uniprot/G6PD_EMENI", "http://www.uniprot.org/uniprot/G6PD_HELPJ", "http://amigo.geneontology.org/amigo/term/GO:0004345", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005954", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019298", "http://www.uniprot.org/uniprot/G6PD_ENCCU", "http://www.uniprot.org/uniprot/G6PD_HUMAN", "http://www.uniprot.org/uniprot/G6PD_DIDVI" ], "type": "yesno", "id": "58a2da4260087bc10a000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226563", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 302, "text": "This genetic defect shows sex linked inheritance and a marked heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10645652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "G6PD deficiency is the most common enzymopathy in the world. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10645652", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 605, "text": "Study of the deficiency pattern amongst family members of the enzyme deficient subjects confirmed the X-linked inheritance of G-6-PD deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1634454", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 706, "text": "This was caused by Glucose-6-Phosphate-Dehydrogenase-Deficiency, which could be demonstrated by a red-cell-enzyme analysis. The investigation of the patient's whole family showed the typical recessive X-linked inheritance of this enzyme-defect. Frequency and clinical manifestations of this defect are discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6350992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "After having described in detail the pathophysiology, symptomatology, X-chromosomal inheritance and some laboratory methods in detecting G-6-PD-deficiency by demonstrating a case of favism (Schulz et al. 1977), the authors now discuss the particularities of the enzyme deficiency in the newborn. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/631693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Severe red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency has been found in an 'aboriginal' Finnish family. 2 male and 9 female carriers of the variant G-6-PD were studied. The genetic pattern is consistent with x-linked recessive inheritance and the defect is associated with drug (primaquine) induced haemolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1188317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "X-linked glucose-6-phosphate dehydrogenase deficiency in Mus musculus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3377761", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9290617", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 309, "text": "Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24943486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "UNLABELLED: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder in which haemolytic anaemia is the major symptom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11271380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent enzyme deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15297240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is transmitted as an X-linked recessive disorder, and thus female infants are expected to be only rarely affected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3810219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Erythrocytic glucose-6-phosphate dehydrogenase (G6PD) of a mutant mouse strain with X-linked G6PD-deficiency was purified and compared with the wildtype G6PD by biochemical and physiological characteristics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1953691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "A mouse with X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency has been recovered in offspring of 1-ethyl-1-nitrosourea-treated male mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3377761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116429", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 359, "text": "Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an X-linked genetic defect, affecting around 400 million people worldwide and is characterized by considerable biochemical and molecular heterogeneity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26139767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked genetic disorder with a relatively high frequency in malaria-endemic regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25771467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26226515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, and it has a significant prevalence in the male population (X chromosome linked)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common X-linked enzymopathy can lead to severe hyperbilirubinemia, acute bilirubin encephalopathy and kernicterus in the United States", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Glucose-6-phosphate dehydrogenase deficiency (G6PD), an x-linked inherited enzymopathy, is a barrier to malaria control because primaquine cannot be readily applied for radical cure in individuals with the condition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23834949", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 480, "text": "G6PD deficiency has an x-linked pattern of inheritance in which hemizygous males are deficient, while females may or may not be deficient depending on the number of affected alleles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26827633", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 298, "text": "Phenotype frequencies and family data verified the X-linked inheritance of the G6PD polymorphism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1296572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme involved in the pentose phosphate pathway, its especially important in red blood cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24943486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme involved in the pentose phosphate pathway, its especially important in red blood cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD. About 400 million people worldwide have a deficiency of this enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24943486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme defect. We report a new variant, G6PD Durham713G, that is associated with chronic nonspherocytic hemolytic anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9290617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, and it has a significant prevalence in the male population (X chromosome linked).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "The human X-linked gene encoding glucose 6-phosphate dehydrogenase (G6PD) is highly polymorphic; more than 300 G6PD variants have been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2912069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked incompletely dominant enzyme deficiency that results from G6PD gene mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24958328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275698", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 297, "text": "Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24943486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "X-linked glucose-6-phosphate dehydrogenase (G6PD) and autosomal 6-phosphogluconate dehydrogenase (6PGD) polymorphisms in baboons.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1296572", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "X-linked glucose-6-phosphate dehydrogenase deficiency in Mus musculus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3377761", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder in which haemolytic anaemia is the major symptom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11271380", "endSection": "abstract" } ] }, { "body": "What is FFI, fatal familial insomnia", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1347910", "http://www.ncbi.nlm.nih.gov/pubmed/23026528", "http://www.ncbi.nlm.nih.gov/pubmed/27943639", "http://www.ncbi.nlm.nih.gov/pubmed/22040318", "http://www.ncbi.nlm.nih.gov/pubmed/12111447", "http://www.ncbi.nlm.nih.gov/pubmed/26074146", "http://www.ncbi.nlm.nih.gov/pubmed/8909448", "http://www.ncbi.nlm.nih.gov/pubmed/11079543", "http://www.ncbi.nlm.nih.gov/pubmed/27056979", "http://www.ncbi.nlm.nih.gov/pubmed/14732629", "http://www.ncbi.nlm.nih.gov/pubmed/16109494", "http://www.ncbi.nlm.nih.gov/pubmed/9270595", "http://www.ncbi.nlm.nih.gov/pubmed/8105681", "http://www.ncbi.nlm.nih.gov/pubmed/24851016", "http://www.ncbi.nlm.nih.gov/pubmed/25473397", "http://www.ncbi.nlm.nih.gov/pubmed/17013786", "http://www.ncbi.nlm.nih.gov/pubmed/9818894" ], "ideal_answer": [ "Familial fatal insomnia (FFI) is a prion disease caused by a mutation (D178N-129M haplotype) in the Prion Protein gene (PRNP). FFI is manifested by sleep disturbances with insomnia, autonomic disorders and spontaneous and evoked myoclonus, among other symptoms. FFI is considered to be a rare disease." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034062", "http://www.disease-ontology.org/api/metadata/DOID:0050433" ], "type": "summary", "id": "58a3160d60087bc10a00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Fatal familial insomnia is a rare disease caused by a D178N mutation in combination with methionine (Met) at codon 129 in the mutated allele of PRNP (D178N-129M haplotype).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27056979", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 306, "text": "FFI is manifested by sleep disturbances with insomnia, autonomic disorders and spontaneous and evoked myoclonus, among other symptoms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27056979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Familial fatal insomnia (FFI) is fatal disorder characterized by damage to select thalamic nuclei, together with progressive insomnia and dysautonomia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26074146", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 568, "text": "Point mutations or the insertions of one or more copies of a 24 bp repeat are associated with familial human prion diseases including familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Str\u00e4ussler-Scheinker syndrome, and fatal familial insomnia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24851016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Fatal familial insomnia (FFI) is a unique hereditary prion disease with characteristic disturbances of sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11079543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Fatal familial insomnia (FFI) is a rare hereditary human prion disease with unique clinical features including progressive sleep impairment and autonomic dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12111447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Fatal familial insomnia (FFI), a condition characterized by inability to sleep, dysautonomia, motor disturbances, and selective thalamic atrophy is a prion disease linked to a GAC----AAC mutation at codon 178 of the prion gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1347910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Fatal familial insomnia (FFI), or familial selective thalamic degeneration with a mutation at codon 178 of the prion protein (PrP) gene, is a rapidly progressive autosomal dominant disease characterized by progressive insomnia, dysautonomia, and myoclonus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8909448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 508, "text": "BACKGROUND: Fatal familial insomnia (FFI) is an autosomal dominant disease linked to a mutation in the prion protein gene. Fatal familial insomnia is characterized by sleep disturbance and loss of neurons, with gliosis in the thalamic nuclei.OBJECTIVE: To describe the clinical, neurophysiological, radiological, and neuropathological data in a Chinese family with FFI.SETTING: Tertiary referral university hospital setting.PATIENTS: Patient 1 was a 36-year-old man who presented with insomnia and myoclonus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14732629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Fatal familial insomnia (FFI) is a rare genetic disease characterized by intractable insomnia, dysautonomia, and dementia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25473397", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 303, "text": "FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8105681", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 463, "text": "FFI is associated with an aspartic acid to asparagine mutation at codon 178 of the PrP gene (D178N) in conjunction with methionine at the codon 129 polymorphic site on the mutant allele (cis-129M).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9270595", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 211, "text": "The propositus had behavioral, sleep, cognitive, and motor impairment associated with thalamic and olivary atrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9818894", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 106, "text": " Sporadic fatal insomnia (sFI) and fatal familial insomnia (FFI) are rare human prion diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22040318", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 164, "text": "Fatal familial insomnia (FFI) is an autosomal dominant prion disease characterized clinically by inattention, sleep loss, dysautonomia, and motor signs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026528", "endSection": "abstract" } ] }, { "body": "Which mutated genes are associated with the Tourette's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23825391", "http://www.ncbi.nlm.nih.gov/pubmed/16224024", "http://www.ncbi.nlm.nih.gov/pubmed/18021920", "http://www.ncbi.nlm.nih.gov/pubmed/23990902", "http://www.ncbi.nlm.nih.gov/pubmed/24411733", "http://www.ncbi.nlm.nih.gov/pubmed/25464894", "http://www.ncbi.nlm.nih.gov/pubmed/20445167", "http://www.ncbi.nlm.nih.gov/pubmed/24978639", "http://www.ncbi.nlm.nih.gov/pubmed/19018236" ], "ideal_answer": [ "A mutation in histidine decarboxylase (Hdc) gene as well as mutations in the SLITRK1 (Slit and Trk-like 1) gene have been implicated as rare genetic causes of Tourette's syndrome." ], "exact_answer": [ [ "histidine decarboxylase", "Hdc" ], [ "Slit and Trk-like 1", "SLITRK1" ] ], "type": "list", "id": "58a7fb2860087bc10a000034", "snippets": [ { "offsetInBeginSection": 276, "offsetInEndSection": 473, "text": " A rare genetic form of Tourette syndrome due to L-histidine-decarboxylase mutation, with similar features in human and rodent, has inspired new research on functional anatomy of Tourette syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24978639", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 280, "text": "A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24411733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24411733", "endSection": "title" }, { "offsetInBeginSection": 225, "offsetInEndSection": 372, "text": "Tourette syndrome (TS), the most severe end of the continuum of tic disorders, is substantially genetic, but causative mutations have been elusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25464894", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 524, "text": "The SLITRK1 gene encodes a developmentally regulated stimulator of neurite outgrowth and previous studies have implicated rare variants in this gene in disorders in the OC spectrum, specifically Tourette syndrome (TS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990902", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 493, "text": "The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23825391", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 467, "text": "we describe an analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20445167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Mutations in the gene SLITRK1 (Slit and Trk-like 1) have been reported in patients with Tourette's disorder (TD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19018236", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 339, "text": "Recently, two variants, including a single-base deletion resulting in a truncated protein and a 3'-untranslated-region variant altering a binding site for micro-RNA in the Slit and Trk-like 1 gene, were found to be a genetic cause of Tourette syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18021920", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 847, "text": "Collectively, these findings support the association of rare SLITRK1 sequence variants with TS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16224024", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by niraparib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27898364", "http://www.ncbi.nlm.nih.gov/pubmed/26217019", "http://www.ncbi.nlm.nih.gov/pubmed/23810788", "http://www.ncbi.nlm.nih.gov/pubmed/23934192", "http://www.ncbi.nlm.nih.gov/pubmed/27141070", "http://www.ncbi.nlm.nih.gov/pubmed/27716873", "http://www.ncbi.nlm.nih.gov/pubmed/27717299", "http://www.ncbi.nlm.nih.gov/pubmed/26351319", "http://www.ncbi.nlm.nih.gov/pubmed/26281686", "http://www.ncbi.nlm.nih.gov/pubmed/25685067", "http://www.ncbi.nlm.nih.gov/pubmed/25758918", "http://www.ncbi.nlm.nih.gov/pubmed/26518726", "http://www.ncbi.nlm.nih.gov/pubmed/26513298", "http://www.ncbi.nlm.nih.gov/pubmed/24970803", "http://www.ncbi.nlm.nih.gov/pubmed/25761096", "http://www.ncbi.nlm.nih.gov/pubmed/27141062", "http://www.ncbi.nlm.nih.gov/pubmed/23118055", "http://www.ncbi.nlm.nih.gov/pubmed/27614696", "http://www.ncbi.nlm.nih.gov/pubmed/24356813", "http://www.ncbi.nlm.nih.gov/pubmed/27810860" ], "ideal_answer": [ "Niraparib is a Poly(ADP-ribose) Polymerase (PARP) Inhibitor. It is used for ovarian cancer treatment." ], "exact_answer": [ "Poly(ADP-ribose) Polymerase" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004789" ], "type": "factoid", "id": "5880be1dc872c95565000007", "snippets": [ { "offsetInBeginSection": 1323, "offsetInEndSection": 1607, "text": "While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27141062", "endSection": "abstract" }, { "offsetInBeginSection": 1219, "offsetInEndSection": 1358, "text": "Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27141070", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 689, "text": "We report here that while the activities of the four human sirtuin isoforms SIRT1, SIRT2, SIRT3 and SIRT6 are blocked by sirtuin inhibitor Ex527 in vitro, they are unaffected by the seven clinical and commonly used PARP inhibitors niraparib, olaparib, rucaparib, talazoparib, veliparib, PJ34, and XAV939. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26518726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Results from a phase III trial indicate that maintenance therapy with the PARP inhibitor niraparib is more effective than placebo in slowing the progression of recurrent platinum-sensitive ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27614696", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 492, "text": "OBJECTIVE: Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal treatment setting remains unknown. We assessed the effect of niraparib on HGSOC patient-derived xenograft (PDX) models as well as the relationship between certain markers of homologous recombination (HR) status, including BRCA1/2 mutations and formation of RAD51 foci after DNA damage, and response of these PDXs to niraparib in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27614696", "endSection": "abstract" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1413, "text": "There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27716873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Background Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27717299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Treatment with the PARP inhibitor, niraparib, sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685067", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 653, "text": "METHODS: Here we examine the response to niraparib, a potent PARP-1/PARP-2 inhibitor currently under clinical evaluation, in MSI versus microsatellite stable (MSS) CRC cell lines in vitro and in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685067", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 483, "text": "Several clinical-stage PARP inhibitors, including veliparib, rucaparib, olaparib, niraparib, and talazoparib, have been evaluated for their PARP-trapping activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25758918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25761096", "endSection": "title" }, { "offsetInBeginSection": 292, "offsetInEndSection": 506, "text": "We describe the rationale for this approach and the design and discovery of niraparib, a potent PARP-1/2 inhibitor with good cell based activity, selectivity for cancer over normal cells, and oral bioavailability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25761096", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1571, "text": "Niraparib (50 mg/kg) inhibited PARP1 activity in vivo and extended survival of mice with orthotopic pHGA xenografts, when administered before IR (20 Gy, fractionated), relative to control mice (40 vs. 25 days)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26351319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Niraparib (MK-4827), a novel poly(ADP-Ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24970803", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810788", "endSection": "title" }, { "offsetInBeginSection": 506, "offsetInEndSection": 800, "text": "Niraparib was characterized in a number of preclinical models before moving to phase I clinical trials, where it showed excellent human pharmacokinetics suitable for once a day oral dosing, achieved its pharmacodynamic target for PARP inhibition, and had promising activity in cancer patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25761096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The aim of this study was to assess niraparib (MK-4827), a novel poly(ADP-Ribose) polymerase (PARP) inhibitor, for its ability to radiosensitize human tumor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24970803", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 280, "text": "Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810788", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 778, "text": "Moreover, the potency in trapping PARP differed markedly among inhibitors with niraparib (MK-4827) > olaparib (AZD-2281) >> veliparib (ABT-888), a pattern not correlated with the catalytic inhibitory properties for each drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118055", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 482, "text": "Several clinical-stage PARP inhibitors, including veliparib, rucaparib, olaparib, niraparib, and talazoparib, have been evaluated for their PARP-trapping activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25758918", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1071, "text": "These results indicate that human tumor cells are significantly radiosensitized by the potent and selective PARP-1 inhibitor, niraparib, in the in vitro setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24970803", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 279, "text": "Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23810788", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 773, "text": "Moreover, the potency in trapping PARP differed markedly among inhibitors with niraparib (MK-4827)>olaparib (AZD-2281)>>veliparib (ABT-888), a pattern not correlated with the catalytic inhibitory properties for each drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118055", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1562, "text": "Niraparib (50 mg/kg) inhibited PARP1 activity in vivo and extended survival of mice with orthotopic pHGA xenografts, when administered before IR (20 Gy, fractionated), relative to control mice (40 vs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26351319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25761096", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Treatment with the PARP inhibitor, niraparib, sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685067", "endSection": "title" }, { "offsetInBeginSection": 558, "offsetInEndSection": 675, "text": "Other PARP inhibitors under clinical trials include rucaparib, niraparib, veliparib, and the \"PARP-trapping\" BMN-673.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26281686", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 844, "text": "The high-throughput screens identified multiple clinical poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors, such as olaparib (AZD-2281), niraparib (MK-4827) and BMN 673, as being selective for ERCC1 deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23934192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Inhibition of Poly(ADP-ribose) Polymerase1 (PARP1) impairs DNA damage repair, and early generation PARP1/2 inhibitors (olaparib, niraparib, etc.) have demonstrated clinical proof of concept for cancer treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26513298", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 777, "text": "Moreover, the potency in trapping PARP differed markedly among inhibitors with niraparib (MK-4827) > olaparib (AZD-2281) >> veliparib (ABT-888), a pattern not correlated with the catalytic inhibitory properties for each drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118055", "endSection": "abstract" } ] }, { "body": "Which peak calling algorithm employs mixture model clustering under the hood?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25223640" ], "ideal_answer": [ "JAMM (Joint Analysis of NGS replicates via Mixture Model clustering) is a peak finder that can integrate information from biological replicates, determine enrichment site widths accurately and resolve neighboring narrow peaks. JAMM is a universal peak finder that is applicable to different types of datasets." ], "exact_answer": [ "JAMM" ], "type": "factoid", "id": "587f760792a5b8ad44000005", "snippets": [ { "offsetInBeginSection": 352, "offsetInEndSection": 946, "text": "We developed JAMM (Joint Analysis of NGS replicates via Mixture Model clustering): a peak finder that can integrate information from biological replicates, determine enrichment site widths accurately and resolve neighboring narrow peaks. JAMM is a universal peak finder that is applicable to different types of datasets. We show that JAMM is among the best performing peak finders in terms of site detection accuracy and in terms of accurate determination of enrichment sites widths. In addition, JAMM's replicate integration improves peak spatial resolution, sorting and peak finding accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25223640", "endSection": "abstract" } ] }, { "body": "Data from which major epigenome projects are contained in the DeepBlue epigenomic data server?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27084938" ], "ideal_answer": [ "The DeepBlue Epigenomic Data Server contains data from four major epigenome projects, namely ENCODE, ROADMAP, BLUEPRINT and DEEP." ], "exact_answer": [ [ "ENCODE" ], [ "ROADMAP" ], [ "BLUEPRINT" ], [ "DEEP" ] ], "type": "list", "id": "588fd8f3621ea6ff7e000001", "snippets": [ { "offsetInBeginSection": 597, "offsetInEndSection": 956, "text": "Here we present the DeepBlue Epigenomic Data Server, which streamlines epigenomic data analysis as well as software development. DeepBlue provides a comprehensive programmatic interface for finding, selecting, filtering, summarizing and downloading region sets. It contains data from four major epigenome projects, namely ENCODE, ROADMAP, BLUEPRINT and DEEP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27084938", "endSection": "abstract" } ] }, { "body": "Which diseases that can be treated using the focused ultrasound thalamotomy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26382842", "http://www.ncbi.nlm.nih.gov/pubmed/25438838", "http://www.ncbi.nlm.nih.gov/pubmed/27822200", "http://www.ncbi.nlm.nih.gov/pubmed/24291848", "http://www.ncbi.nlm.nih.gov/pubmed/25343176", "http://www.ncbi.nlm.nih.gov/pubmed/25512869", "http://www.ncbi.nlm.nih.gov/pubmed/24876191", "http://www.ncbi.nlm.nih.gov/pubmed/27399411", "http://www.ncbi.nlm.nih.gov/pubmed/26499271", "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "http://www.ncbi.nlm.nih.gov/pubmed/24620914", "http://www.ncbi.nlm.nih.gov/pubmed/20033983", "http://www.ncbi.nlm.nih.gov/pubmed/22208894", "http://www.ncbi.nlm.nih.gov/pubmed/23523144", "http://www.ncbi.nlm.nih.gov/pubmed/26769606", "http://www.ncbi.nlm.nih.gov/pubmed/27557301", "http://www.ncbi.nlm.nih.gov/pubmed/24761224", "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "http://www.ncbi.nlm.nih.gov/pubmed/26877873" ], "ideal_answer": [ "Focused ultrasound thalamotomy is used for treatment of Parkinson disease, essential tremor, obsessive-compulsive disorder and chronic neuropathic pain." ], "exact_answer": [ [ "Parkinson disease" ], [ "essential tremor" ], [ "obsessive-compulsive disorder" ], [ "chronic neuropathic pain" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057086" ], "type": "list", "id": "58846be0e56acf5176000005", "snippets": [ { "offsetInBeginSection": 718, "offsetInEndSection": 927, "text": "Besides DBS and standard thalamotomy, novel surgical approaches for ET are on the horizon. The development of MRI-guided focused ultrasound technique has been the new frontier of deep brain lesional therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26382842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "132\u2003A Randomized, Sham-Controlled Trial of Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Trial for the Treatment of Tremor-Dominant, Idiopathic Parkinson Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399411", "endSection": "title" }, { "offsetInBeginSection": 158, "offsetInEndSection": 442, "text": "Recently, transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been used to successfully perform thalamotomy for essential tremor. We designed a double-blinded, randomized controlled trial to investigate the effectiveness of MRgFUS thalamotomy in tremor-dominant PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "Thalamotomy at the ventralis intermedius nucleus has been an effective treatment method for essential tremor, but how the brain network changes immediately responding to this deliberate lesion and then reorganizes afterwards are not clear. Taking advantage of a non-cranium-opening MRI-guided focused ultrasound ablation technique, we investigated functional network changes due to a focal lesion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24876191", "endSection": "title" }, { "offsetInBeginSection": 1482, "offsetInEndSection": 1637, "text": "CONCLUSIONS: Our results demonstrate that MRgFUS thalamotomy is a safe, effective and less-invasive surgical method for treating medication-refractory ET. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24876191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "OBJECT: The authors report different MRI patterns in patients with essential tremor (ET) or obsessive-compulsive disorder (OCD) after transcranial MR-guided focused ultrasound (MRgFUS) and discuss possible causes of occasional MRgFUS failure.METHODS: Between March 2012 and August 2013, MRgFUS was used to perform unilateral thalamotomy in 11 ET patients and bilateral anterior limb capsulotomy in 6 OCD patients; in all patients symptoms were refractory to drug therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25343176", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 421, "text": "To discern the neurophysiologic correlates of its therapeutic effects, we applied MRgHIFU to an intractable neurologic disorder, essential tremor, while measuring magnetoencephalogram mu rhythms from the motor cortex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25438838", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "endSection": "title" }, { "offsetInBeginSection": 88, "offsetInEndSection": 416, "text": "Methods. Seven PD patients, mean age 59.4 \u00b1 9.8 years (range, 46-74) with a mean disease duration of 5.4 \u00b1 2.8 years (range, 2-10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1078, "text": "Thalamotomy using MRgFUS is safe and effective in PD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Evolution of Movement Disorders Surgery Leading to Contemporary Focused Ultrasound Therapy for Tremor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26499271", "endSection": "title" }, { "offsetInBeginSection": 338, "offsetInEndSection": 463, "text": "A noninvasive approach using transcranial high-energy focused ultrasound has emerged for the treatment of intractable tremor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26499271", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 775, "text": "This article describes the evolution of magnetic resonance-guided focused ultrasound for ventrolateral thalamotomy for tremor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26499271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Thalamic connectivity in patients with essential tremor treated with MR imaging-guided focused ultrasound: in vivo fiber tracking by using diffusion-tensor MR imaging.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24620914", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 763, "text": "PURPOSE: To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement.MATERIALS AND METHODS: With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24620914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "A pilot study of focused ultrasound thalamotomy for essential tremor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "endSection": "title" }, { "offsetInBeginSection": 168, "offsetInEndSection": 585, "text": "This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor.METHODS: From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1729, "text": "CONCLUSIONS: In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523144", "endSection": "title" }, { "offsetInBeginSection": 383, "offsetInEndSection": 566, "text": "MR-guided focused ultrasound has been developed as a non-invasive means of generating precisely placed focal lesions. We examined its application to the management of essential tremor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523144", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 818, "text": "Four patients with chronic and medication-resistant essential tremor were treated with MR-guided focused ultrasound to ablate tremor-mediating areas of the thalamus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523144", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1739, "text": "INTERPRETATION: MR-guided focused ultrasound might be a safe and effective approach to generation of focal intracranial lesions for the management of disabling, medication-resistant essential tremor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22208894", "endSection": "title" }, { "offsetInBeginSection": 147, "offsetInEndSection": 493, "text": "The goal of this study was to apply the new transcranial magnetic resonance imaging-guided focused ultrasound (tcMRgFUS) technology to perform noninvasive central lateral thalamotomies (CLTs) as a treatment for chronic neuropathic pain.METHODS: In 12 patients suffering from chronic therapy-resistant neuropathic pain, tcMRgFUS CLT was proposed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22208894", "endSection": "abstract" }, { "offsetInBeginSection": 2063, "offsetInEndSection": 2225, "text": "CONCLUSIONS: The authors assert that tcMRgFUS represents a noninvasive, precise, and radiation-free neurosurgical technique for the treatment of neuropathic pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22208894", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 585, "text": "A new less invasive treatment of tremor using MR guided focused ultrasound has started and is promising.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291848", "endSection": "abstract" }, { "offsetInBeginSection": 1541, "offsetInEndSection": 1729, "text": "Quality-of-life scores improved from 37% to 11% (P=0.001).CONCLUSIONS: In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 413, "text": "Seven PD patients, mean age 59.4 \u00b1 9.8 years (range, 46-74) with a mean disease duration of 5.4 \u00b1 2.8 years (range, 2-10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 975, "text": "We hypothesized that all three would effectively treat the dominant hand and positively impact functional outcomes and quality of life as measured with the Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire.This is a retrospective study of medication-refractory essential tremor patients treated at the University of Virginia with bilateral Vim DBS (n\u2009=\u200957), unilateral Vim DBS (n\u2009=\u200913), or unilateral focused ultrasound Vim thalamotomy (n\u2009=\u200915)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26769606", "endSection": "abstract" }, { "offsetInBeginSection": 1510, "offsetInEndSection": 1684, "text": "Quality-of-life scores improved from 37% to 11% (P=0.001).In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinsons Disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "endSection": "title" }, { "offsetInBeginSection": 97, "offsetInEndSection": 415, "text": "Seven PD patients, mean age 59.4 \u00b1 9.8 years (range, 46-74) with a mean disease duration of 5.4 \u00b1 2.8 years (range, 2-10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 553, "text": "Transcranial magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) is gaining attention as a potent substitute for surgical intervention in the treatment of neurologic disorders. To discern the neurophysiologic correlates of its therapeutic effects, we applied MRgHIFU to an intractable neurologic disorder, essential tremor, while measuring magnetoencephalogram mu rhythms from the motor cortex. Focused ultrasound sonication destroyed tissues by focusing a high-energy beam on the ventralis intermedius nucleus of the thalamus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25438838", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 585, "text": "BACKGROUND: Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor.METHODS: From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421209", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "132\u2003A Randomized, Sham-Controlled Trial of Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Trial for the Treatment of Tremor-Dominant, Idiopathic Parkinson Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399411", "endSection": "title" }, { "offsetInBeginSection": 1572, "offsetInEndSection": 1689, "text": "In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23944301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27557301", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523144", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24876191", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Functional assessment and quality of life in essential tremor with bilateral or unilateral DBS and focused ultrasound thalamotomy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26769606", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22208894", "endSection": "title" }, { "offsetInBeginSection": 738, "offsetInEndSection": 977, "text": "This is a retrospective study of medication-refractory essential tremor patients treated at the University of Virginia with bilateral Vim DBS (n\u2009=\u200957), unilateral Vim DBS (n\u2009=\u200913), or unilateral focused ultrasound Vim thalamotomy (n\u2009=\u200915).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26769606", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 776, "text": "Twenty-one consecutive patients suffering from chronic (mean disease duration 29.9\u00a0years), therapy-resistant ET were treated with MRgFUS CTT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26877873", "endSection": "abstract" } ] }, { "body": "Is the toxin produced by Clostridium botulinum always deadly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22513950", "http://www.ncbi.nlm.nih.gov/pubmed/20173718", "http://www.ncbi.nlm.nih.gov/pubmed/23871478", "http://www.ncbi.nlm.nih.gov/pubmed/26866491", "http://www.ncbi.nlm.nih.gov/pubmed/19488551", "http://www.ncbi.nlm.nih.gov/pubmed/15244362", "http://www.ncbi.nlm.nih.gov/pubmed/24997242", "http://www.ncbi.nlm.nih.gov/pubmed/23097586", "http://www.ncbi.nlm.nih.gov/pubmed/12926199", "http://www.ncbi.nlm.nih.gov/pubmed/24867833", "http://www.ncbi.nlm.nih.gov/pubmed/17674683", "http://www.ncbi.nlm.nih.gov/pubmed/20693440", "http://www.ncbi.nlm.nih.gov/pubmed/19160335", "http://www.ncbi.nlm.nih.gov/pubmed/26697417" ], "ideal_answer": [ "There are numerous examples where children and animals survived infection with clostridium botulinum." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001905", "http://www.disease-ontology.org/api/metadata/DOID:11976" ], "type": "yesno", "id": "58a341a660087bc10a000017", "snippets": [ { "offsetInBeginSection": 1759, "offsetInEndSection": 1941, "text": "Animals treated with trace elements recovered. It appears that intestinal microbiota dysbiosis and trace element deficiency could explain the extensive emergence of chronic Botulism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24997242", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1316, "text": "The patient was treated with human botulism immune globulin and had rapid recovery in weakness. A stool sample from the patient was positive for Type A Clostridium botulinum toxin eventually confirming the diagnosis of infant botulism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26697417", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1363, "text": "The botulism immunoglobulin was administered, and a diagnosis was confirmed with positive botulinum toxin in the stool samples. Full recovery was made by the infant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23871478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Botulinum neurotoxin (BoNT) serotype B (BoNT/B) is one of the serotypes of BoNT that causes deadly human botulism, though it is used clinically for treatment of many neuromuscular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20693440", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 311, "text": "Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23097586", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 692, "text": "To assess the effectiveness and safety of botulinum toxin in treating MPS, excluding MPS in neck and head muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513950", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 174, "text": "Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19488551", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 751, "text": " An emerging treatment option to address these issues is the use of a paralyzing material such as botulinum toxin A (Botox) to decrease the appearance of the wrinkles, which yields a more esthetic and youthful facial appearanc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17674683", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 413, "text": "lthough BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26866491", "endSection": "abstract" } ] }, { "body": "Is ocrelizumab effective for treatment of multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27270678", "http://www.ncbi.nlm.nih.gov/pubmed/26788130", "http://www.ncbi.nlm.nih.gov/pubmed/24494635", "http://www.ncbi.nlm.nih.gov/pubmed/27116720", "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "http://www.ncbi.nlm.nih.gov/pubmed/25887773", "http://www.ncbi.nlm.nih.gov/pubmed/26600872", "http://www.ncbi.nlm.nih.gov/pubmed/27718747", "http://www.ncbi.nlm.nih.gov/pubmed/24494619", "http://www.ncbi.nlm.nih.gov/pubmed/27552111", "http://www.ncbi.nlm.nih.gov/pubmed/27813441", "http://www.ncbi.nlm.nih.gov/pubmed/18951300", "http://www.ncbi.nlm.nih.gov/pubmed/24732658", "http://www.ncbi.nlm.nih.gov/pubmed/27389598", "http://www.ncbi.nlm.nih.gov/pubmed/25888198", "http://www.ncbi.nlm.nih.gov/pubmed/23609782", "http://www.ncbi.nlm.nih.gov/pubmed/22229582", "http://www.ncbi.nlm.nih.gov/pubmed/25887766", "http://www.ncbi.nlm.nih.gov/pubmed/26729332", "http://www.ncbi.nlm.nih.gov/pubmed/24928997", "http://www.ncbi.nlm.nih.gov/pubmed/20500147", "http://www.ncbi.nlm.nih.gov/pubmed/27756172", "http://www.ncbi.nlm.nih.gov/pubmed/26702336", "http://www.ncbi.nlm.nih.gov/pubmed/22673950", "http://www.ncbi.nlm.nih.gov/pubmed/21341224", "http://www.ncbi.nlm.nih.gov/pubmed/25732947", "http://www.ncbi.nlm.nih.gov/pubmed/24507535" ], "ideal_answer": [ "Yes, ocrelizumab is effective for primary progressive form of multiple sclerosis." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4002285", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103", "http://www.disease-ontology.org/api/metadata/DOID:2377" ], "type": "yesno", "id": "588fa4b9ed9bbee70d000006", "snippets": [ { "offsetInBeginSection": 672, "offsetInEndSection": 995, "text": " Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27270678", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 903, "text": " Expert commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27813441", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1124, "text": "Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27389598", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552111", "endSection": "title" }, { "offsetInBeginSection": 737, "offsetInEndSection": 959, "text": "Expert commentary: The topline results of two phase-III randomized clinical trials demonstrate superiority of ocrelizumab over interferon beta in RRMS patients with regards to clinical and paraclinical outcome parameters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552111", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1109, "text": "The efficacy of three of them, rituximab, ocrelizumab and ofatumumab in MS has been confirmed by placebo-controlled clinical trials demonstrating a significant reduction of the annualized relapsing rate (ARR), new gadolinium-enhancing (GdE) and T2 lesions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27718747", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1291, "text": "Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod and anti-B-cell therapy ocrelizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887766", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 407, "text": "RECENT FINDINGS: Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-\u03b2-1a, and three times weekly glatiramer acetate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "To summarize mechanisms of action, efficacy, and safety of novel and imminently emerging disease-modifying treatments (DMTs) intended to be used in relapsing-remitting multiple sclerosis (RRMS).Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-\u03b2-1a, and three times weekly glatiramer acetate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "endSection": "title" }, { "offsetInBeginSection": 84, "offsetInEndSection": 260, "text": "We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24928997", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1234, "text": "Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.Most of the presented cell-depleting and myeloablative therapies are highly effective treatment options but are also accompanied by significant risks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27389598", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1288, "text": "The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-\u03b2 and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24732658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 700, "text": "BACKGROUND: B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis.METHODS: We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 \u00ecg) once a week.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552111", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26788130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22047971", "endSection": "title" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1087, "text": "Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27389598", "endSection": "abstract" } ] }, { "body": "Elaborate on the role of CARMEN in cardiac specification.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26423156" ], "ideal_answer": [ "CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA, is a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). CARMEN expression is activated during pathological remodeling in the mouse and human hearts, and is necessary for maintaining cardiac identity in differentiated cardiomyocytes." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:2000043", "http://amigo.geneontology.org/amigo/term/GO:0060912" ], "type": "summary", "id": "58837dd72305cd7e21000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26423156", "endSection": "title" }, { "offsetInBeginSection": 575, "offsetInEndSection": 1487, "text": "One of the most upregulated lncRNAs was a SE-associated lncRNA that was named CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. Interestingly, CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). We demonstrate that CARMEN knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of MIR-143 and -145 expression, two microRNAs located proximal to the enhancer sequences. Importantly, CARMEN expression was activated during pathological remodeling in the mouse and human hearts, and was necessary for maintaining cardiac identity in differentiated cardiomyocytes. This study demonstrates therefore that CARMEN is a crucial regulator of cardiac cell differentiation and homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26423156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26423156", "endSection": "title" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1176, "text": "We demonstrate that CARMEN knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of MIR-143 and -145 expression, two microRNAs located proximal to the enhancer sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26423156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26423156", "endSection": "title" } ] }, { "body": "Is there a role of regorafenib for sarcoma treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24266804", "http://www.ncbi.nlm.nih.gov/pubmed/26266019", "http://www.ncbi.nlm.nih.gov/pubmed/25301268", "http://www.ncbi.nlm.nih.gov/pubmed/27751846", "http://www.ncbi.nlm.nih.gov/pubmed/26907871", "http://www.ncbi.nlm.nih.gov/pubmed/24756792", "http://www.ncbi.nlm.nih.gov/pubmed/25884155" ], "ideal_answer": [ "Yes, there is evidence to suggest that regorafenib can be effective for sarcoma treatment. Clinical trials are under-way." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1115", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012509", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380" ], "type": "yesno", "id": "58848a13e56acf517600000d", "snippets": [ { "offsetInBeginSection": 809, "offsetInEndSection": 862, "text": "Regorafenib has been approved for third-line therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26907871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Study protocol of REGOSARC trial: activity and safety of regorafenib in advanced soft tissue sarcoma: a multinational, randomized, placebo-controlled, phase II trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25884155", "endSection": "title" }, { "offsetInBeginSection": 1795, "offsetInEndSection": 1972, "text": "DISCUSSION: The design of this trial allows an assessment of regorafenib activity over placebo in four sarcoma strata and might provide evidence for launching a phase III trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25884155", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 533, "text": "This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26266019", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 718, "text": "Thus, the Phase III studies with pazopanib, regorafenib, muramyl tripeptide (MTP) and ridaforolimus are extensively discussed as well as the biological rationale for the use of these compounds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24266804", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 935, "text": "Currently, regorafenib is examined in several clinical trials (mostly phase II) in different tumor entities, including renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and soft tissue sarcoma (STS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24756792", "endSection": "abstract" }, { "offsetInBeginSection": 1674, "offsetInEndSection": 1852, "text": "Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib and regorafenib with a corresponding increase in ALDHbright cells (P<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301268", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1299, "text": "Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301268", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 1299, "text": "We evaluated survival and CSC phenotype in mice harboring sarcoma metastases after TKI therapy. We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301268", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 1299, "text": "We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301268", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 1396, "text": "We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05). In contrast, we observed negligible effects on viability and CSC sub-populations with pazopanib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301268", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1275, "text": "After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P < 0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301268", "endSection": "abstract" } ] }, { "body": "Which drug was tested in the TEMSO Trial for multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21991951", "http://www.ncbi.nlm.nih.gov/pubmed/24321165", "http://www.ncbi.nlm.nih.gov/pubmed/23852658", "http://www.ncbi.nlm.nih.gov/pubmed/27937746", "http://www.ncbi.nlm.nih.gov/pubmed/26944956", "http://www.ncbi.nlm.nih.gov/pubmed/26758290", "http://www.ncbi.nlm.nih.gov/pubmed/22723573", "http://www.ncbi.nlm.nih.gov/pubmed/21157651", "http://www.ncbi.nlm.nih.gov/pubmed/26434194", "http://www.ncbi.nlm.nih.gov/pubmed/26865517", "http://www.ncbi.nlm.nih.gov/pubmed/26365096", "http://www.ncbi.nlm.nih.gov/pubmed/23695001", "http://www.ncbi.nlm.nih.gov/pubmed/27919491" ], "ideal_answer": [ "Teriflunomide was evaluated in the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial." ], "exact_answer": [ "Teriflunomide" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017428", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103", "http://www.disease-ontology.org/api/metadata/DOID:2377" ], "type": "factoid", "id": "589a246078275d0c4a00002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865517", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "OBJECTIVE: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865517", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1556, "text": "CONCLUSIONS: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865517", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 830, "text": "Teriflunomide, approved on the basis of the two placebo-controlled trials TEMSO and TOWER, demonstrated a reduction in the ARR from 0.54 to 0.37 and from 0.50 to 0.32 respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26944956", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 964, "text": "Using data from pivotal studies of DMF (DEFINE, NCT00420212; CONFIRM, NCT00451451), fingolimod (FREEDOMS, NCT00289978; FREEDOMS II, NCT00355134), and teriflunomide (TEMSO, NCT00134563; TOWER, NCT00751881), we calculated NNTs to prevent any relapse, more severe relapses (such as those leading to hospitalization or requiring intravenous corticosteroids), and disability worsening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27919491", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 488, "text": "METHODS: In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26365096", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1362, "text": "In the TEMSO and TOWER studies, the 14-mg dose of teriflunomide significantly reduced annualized relapse rate (31% and 36% relative risk reduction compared with placebo, respectively; both P<0.001) and risk of disability progression sustained for 12 weeks (hazard ratio vs placebo 0.70 and 0.69, respectively; both P<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26365096", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1758, "text": "Teriflunomide treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26365096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 468, "text": "The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes.In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26365096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 589, "text": "The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients.The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups.RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 623, "text": "BACKGROUND: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients.OBJECTIVE: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups.METHODS: RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 469, "text": "The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes.In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26365096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 590, "text": "The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients.The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups.RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).A total of 742 patients entered the extension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 622, "text": "BACKGROUND: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients.OBJECTIVE: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups.METHODS: RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22723573", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 627, "text": "Two phase III clinical trials (TEMSO, TOWER) tested teriflunomide in patients with relapsing forms of MS: efficacy was shown, with positive effects on relapse rates and disease progression for 14 mg/day.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865517", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 470, "text": "In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26365096", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of peginesatide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22406924", "http://www.ncbi.nlm.nih.gov/pubmed/24748667", "http://www.ncbi.nlm.nih.gov/pubmed/24905967", "http://www.ncbi.nlm.nih.gov/pubmed/23840463", "http://www.ncbi.nlm.nih.gov/pubmed/27551882", "http://www.ncbi.nlm.nih.gov/pubmed/22935486", "http://www.ncbi.nlm.nih.gov/pubmed/23675762", "http://www.ncbi.nlm.nih.gov/pubmed/23318685", "http://www.ncbi.nlm.nih.gov/pubmed/20730698", "http://www.ncbi.nlm.nih.gov/pubmed/21290916", "http://www.ncbi.nlm.nih.gov/pubmed/23111861", "http://www.ncbi.nlm.nih.gov/pubmed/23343062", "http://www.ncbi.nlm.nih.gov/pubmed/26122516", "http://www.ncbi.nlm.nih.gov/pubmed/26079829", "http://www.ncbi.nlm.nih.gov/pubmed/23343061", "http://www.ncbi.nlm.nih.gov/pubmed/22188389", "http://www.ncbi.nlm.nih.gov/pubmed/23847411", "http://www.ncbi.nlm.nih.gov/pubmed/22719216", "http://www.ncbi.nlm.nih.gov/pubmed/22192713", "http://www.ncbi.nlm.nih.gov/pubmed/21710591", "http://www.ncbi.nlm.nih.gov/pubmed/21816551", "http://www.ncbi.nlm.nih.gov/pubmed/23989045", "http://www.ncbi.nlm.nih.gov/pubmed/24023516", "http://www.ncbi.nlm.nih.gov/pubmed/22884786", "http://www.ncbi.nlm.nih.gov/pubmed/24584613", "http://www.ncbi.nlm.nih.gov/pubmed/27279382", "http://www.ncbi.nlm.nih.gov/pubmed/22592927", "http://www.ncbi.nlm.nih.gov/pubmed/24348017", "http://www.ncbi.nlm.nih.gov/pubmed/23506424", "http://www.ncbi.nlm.nih.gov/pubmed/23338536", "http://www.ncbi.nlm.nih.gov/pubmed/21649477", "http://www.ncbi.nlm.nih.gov/pubmed/23243269", "http://www.ncbi.nlm.nih.gov/pubmed/22642238", "http://www.ncbi.nlm.nih.gov/pubmed/22971699", "http://www.ncbi.nlm.nih.gov/pubmed/27174804", "http://www.ncbi.nlm.nih.gov/pubmed/21940838", "http://www.ncbi.nlm.nih.gov/pubmed/22745925" ], "ideal_answer": [ "Peginesatide (Omontys) is synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent that is designed to specifically stimulate the erythropoietin receptor. It was recalled because of serious side-effects including cases of death." ], "type": "summary", "id": "58962dac78275d0c4a000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "The erythropoietin-mimetic peptide (EMP) peginesatide belongs to the group of erythropoiesis-stimulating agents (ESAs) that are prohibited when misused in sports. Peginesatide is a synthetic pegylated homodimer of two cyclic 21-amino acid chains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27279382", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1120, "text": "Epo mimetic peptides have also raised expectations. Yet the prototype peginesatide was recalled after just 1 year of its widespread use in the USA because of serious side-effects including cases of death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24748667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The erythropoietin analog peginesatide was withdrawn from marketing due to unexpected severe anaphylactic reactions associated with administration of the multi-use formulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26079829", "endSection": "abstract" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1486, "text": "Method characterization was conducted for the EMP-based drug peginesatide concerning specificity, linearity, precision, recovery, stability, ion suppression/enhancement, and limit of detection (LOD, 0.25 ng/mL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "PURPOSE: Peginesatide, a long-acting erythropoiesis-stimulating agent, was recalled in February 2013 following reports of serious and sometimes fatal hypersensitivity reactions in dialysis patients who received a first dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND AND OBJECTIVES: Peginesatide (Omontys) is a novel, synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent (ESA) that is designed to specifically stimulate the erythropoietin receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23243269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318685", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 973, "text": "Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22935486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Peginesatide is a synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent (ESA) that may have therapeutic potential for anemia in patients with advanced chronic kidney disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23343062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "The pharmacokinetics (PK) (absorption, distribution, metabolism, excretion) of peginesatide, a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA), was evaluated in rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22188389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22188389", "endSection": "title" }, { "offsetInBeginSection": 119, "offsetInEndSection": 244, "text": "Peginesatide is an investigational pegylated, peptide-based, once-monthly ESA for increasing and maintaining hemoglobin (Hb).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21290916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Peginesatide: a potential erythropoiesis stimulating agent for the treatment of anemia of chronic renal failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21290916", "endSection": "title" }, { "offsetInBeginSection": 749, "offsetInEndSection": 1069, "text": "Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. It is undetectable using current anti-doping tests due to its lack of sequence homology to EPO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 364, "text": "Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis. Studies were designed to determine the erythropoietic response, pharmacokinetics (PK), tissue distribution, metabolism, and excretion of peginesatide in nonhuman primates following a single i.v.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis. Studies were designed to determine the erythropoietic response, pharmacokinetics (PK), tissue distribution, metabolism, and excretion of peginesatide in nonhuman primates following a single i.v. dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23318685", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 1313, "text": "Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. It is undetectable using current anti-doping tests due to its lack of sequence homology to EPO. To detect and deter potential abuse of peginesatide, we initiated an industry/antidoping laboratory collaboration to develop and validate screening and confirmation assays so that they would be available before peginesatide reaches the market.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 490, "text": "Peginesatide is a synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. Peginesatide has a unique structure that consists of a synthetic peptide dimer (with no sequence similarity to erythropoietin) conjugated to a 40-kDa PEG moiety. Peginesatide is being developed for the treatment of anemia associated with chronic kidney disease in dialysis patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "Peginesatide is a synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. Peginesatide has a unique structure that consists of a synthetic peptide dimer (with no sequence similarity to erythropoietin) conjugated to a 40-kDa PEG moiety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22406924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Peginesatide: a potential erythropoiesis stimulating agent for the treatment of anemia of chronic renal failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21290916", "endSection": "title" } ] }, { "body": "Describe mechanism of action of Eteplirsen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27807823", "http://www.ncbi.nlm.nih.gov/pubmed/27854228", "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "http://www.ncbi.nlm.nih.gov/pubmed/27936976", "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "http://www.ncbi.nlm.nih.gov/pubmed/26573217", "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "http://www.ncbi.nlm.nih.gov/pubmed/24282529" ], "ideal_answer": [ "Eteplirsen (Exondys 51) is an antisense oligonucleotide designed to induce exon 51 skipping. Eteplirsen is approved for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene amenable to exon 51 skipping." ], "type": "summary", "id": "5891869b621ea6ff7e00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Eteplirsen (Exondys\u00a051) is an antisense oligonucleotide designed to induce exon 51 skipping that is developed by Sarepta Therapeutics. Intravenous eteplirsen has received accelerated approval from the US FDA for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene amenable to exon 51 skipping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27807823", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 563, "text": "The first AON (eteplirsen) has recently received accelerated approval by the Food and Drug Administration in the US.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27936976", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 645, "text": "Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "OBJECTIVE: In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1241, "text": "We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24282529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Exon skipping quantification by quantitative reverse-transcription polymerase chain reaction in Duchenne muscular dystrophy patients treated with the antisense oligomer eteplirsen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "To continue evaluation of the long-term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26573217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 638, "text": "The present study used a double-blind placebo-controlled protocol to test eteplirsen's ability to induce dystrophin production and improve distance walked on the 6-minute walk test (6MWT).DMD boys aged 7 to 13 years, with confirmed deletions correctable by skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 weeks (n\u2009=\u20094/group).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 1002, "text": "Here we describe the development of a Taqman quantitative (q)RT-PCR assay to quantify exon skipping and highlight its use to determine the levels of exon skipping in DMD patients treated intramuscularly with a morpholino AO to skip exon 51, eteplirsen (AVI-4658).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "endSection": "abstract" }, { "offsetInBeginSection": 1462, "offsetInEndSection": 1783, "text": "The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.Over 3 years of follow-up, eteplirsen-treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC.\u00a9 2016 The Authors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26573217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 382, "text": "We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" } ] }, { "body": "Which genes of the marmoset genome exhibit rapid sequence evolution?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25038751" ], "ideal_answer": [ "Both protein-coding and microRNA genes related to reproduction exhibit evidence of rapid sequence evolution in the marmoset genome." ], "exact_answer": [ [ "protein-coding genes related to reproduction" ], [ "microRNA genes related to reproduction" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019143", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005075", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019020" ], "type": "list", "id": "58839d892305cd7e21000006", "snippets": [ { "offsetInBeginSection": 494, "offsetInEndSection": 864, "text": "We observed positive selection in growth hormone/insulin-like growth factor genes (growth pathways), respiratory complex I genes (metabolic pathways), and genes encoding immunobiological factors and proteases (reproductive and immunity pathways). In addition, both protein-coding and microRNA genes related to reproduction exhibited evidence of rapid sequence evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25038751", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 864, "text": "In addition, both protein-coding and microRNA genes related to reproduction exhibited evidence of rapid sequence evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25038751", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 865, "text": "In addition, both protein-coding and microRNA genes related to reproduction exhibited evidence of rapid sequence evolution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25038751", "endSection": "abstract" } ] }, { "body": "What is the importance of Janus Kinases in dermatology?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12794134", "http://www.ncbi.nlm.nih.gov/pubmed/27692733", "http://www.ncbi.nlm.nih.gov/pubmed/24825142", "http://www.ncbi.nlm.nih.gov/pubmed/24131352", "http://www.ncbi.nlm.nih.gov/pubmed/8022486", "http://www.ncbi.nlm.nih.gov/pubmed/26800231", "http://www.ncbi.nlm.nih.gov/pubmed/23294276", "http://www.ncbi.nlm.nih.gov/pubmed/26051365", "http://www.ncbi.nlm.nih.gov/pubmed/21347402", "http://www.ncbi.nlm.nih.gov/pubmed/25129481", "http://www.ncbi.nlm.nih.gov/pubmed/26345342", "http://www.ncbi.nlm.nih.gov/pubmed/23829933", "http://www.ncbi.nlm.nih.gov/pubmed/26899199", "http://www.ncbi.nlm.nih.gov/pubmed/19234192" ], "ideal_answer": [ "Janus Kinase (JAK) is active in many skin diseases and recent evidence show that inhibitors of JAK kinase could be used to treat vitiligo, psoriasis, lupus, alopecia areata and other inflammatory skin diseases.", "Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis" ], "type": "summary", "id": "58a3261e60087bc10a00000c", "snippets": [ { "offsetInBeginSection": 76, "offsetInEndSection": 205, "text": "Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26051365", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1409, "text": "Taken together, our results provided new evidence for the effectiveness of EGCG in vitiligo treatment and supported JAK2 as a molecular target for vitiligo medicine development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26345342", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1656, "text": "Notably, three patients treated with oral ruxolitinib, an inhibitor of JAK1 and JAK2, achieved near-complete hair regrowth within 5 months of treatment, suggesting the potential clinical utility of JAK inhibition in human AA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129481", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 708, "text": "Jaks have recently gained significant attention as therapeutic targets in inflammation and autoimmunity, and several Jak inhibitory small molecules have been developed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24131352", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1099, "text": "Efficacy and safety data suggest that some of these oral Jak inhibitors as well as their topical formulations may soon enter the daily clinical practice for treating patients with psoriasis, lupus erythematosus or other inflammatory skin diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24131352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase essential for signaling via cytokine receptors that comprise the common gamma-chain (gammac), i.e., the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12794134", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1429, "text": "Systemically administered pharmacological inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream effectors of the IFN-\u03b3 and \u03b3c cytokine receptors, eliminated the IFN signature and prevented the development of AA, while topical administration promoted hair regrowth and reversed established disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis.We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis.Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26899199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 498, "text": "Plaque psoriasis is a chronic and often debilitating skin disorder and proinflammatory cytokines are known to play a key role in the disease process.To evaluate the safety and efficacy of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis in a randomized, double-blind, placebo-controlled, dose-ranging phase 2b study.Patients were randomized (n = 271) to receive placebo or oral baricitinib at 2, 4, 8 or 10 mg once daily for 12 weeks (Part A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26800231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Oclacitinib (Apoquel(\u00ae) ) inhibits the function of a variety of pro-inflammatory, pro-allergic and pruritogenic cytokines that are dependent on Janus kinase enzyme activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23829933", "endSection": "abstract" }, { "offsetInBeginSection": 38, "offsetInEndSection": 642, "text": "the Janus kinase/signal transducer and activator of transcription (JAK-STAT) cytokine signalling mechanism in disease pathogenesis. This signalling pathway is involved in haematopoiesis and immune development. Mutations in genes regulating JAK-STAT signalling can cause common inflammatory disorders and myeloproliferative disorders. JAK and STAT inhibitors are new management tools for disorders such as myelofibrosis and rheumatoid arthritis. Evidence suggests that the cytokine components of the JAK-STAT pathways play a crucial role in common skin disorders, including psoriasis and atopic dermatitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24825142", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 102, "text": "Tofacitinib is an oral Janus kinase inhibitor that improves clinical measures of psoriasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27692733", "endSection": "abstract" } ] }, { "body": "What is the incidence of beta-thalassemia in Greek population?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1620378", "http://www.ncbi.nlm.nih.gov/pubmed/12091129", "http://www.ncbi.nlm.nih.gov/pubmed/7590514" ], "ideal_answer": [ "The incidence of beta-thalassemia trait is 8% in Greek population." ], "exact_answer": [ "8%" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10241", "http://www.disease-ontology.org/api/metadata/DOID:12241", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013789", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011153", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015994", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017086" ], "type": "factoid", "id": "58a2df9c60087bc10a000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Hemoglobinopathies are very common in Greece, the incidence of beta-thalassemia trait being 8% and that of sickle cell trait ranging from 1 to 32% in various districts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12091129", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 982, "text": "No statistically significant differences were found in the frequency of beta-thalassaemia trait between control subjects (8.49%) and the whole Greek population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7590514", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 798, "text": "beta-Thalassemia was found with an average incidence of 5.476% and alpha-Thalassemia with an incidence of 0.201%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1620378", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 797, "text": "Following this program, 64,814 recruits, representing 0.651% of the total Greek population and 9.917% of the 20-year-old Greek male population, were tested. beta-Thalassemia was found with an average incidence of 5.476% and alpha-Thalassemia with an incidence of 0.201%", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1620378", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 798, "text": "Following this program, 64,814 recruits, representing 0.651% of the total Greek population and 9.917% of the 20-year-old Greek male population, were tested. beta-Thalassemia was found with an average incidence of 5.476% and alpha-Thalassemia with an incidence of 0.201%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1620378", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 906, "text": "Following this program, 64,814 recruits, representing 0.651% of the total Greek population and 9.917% of the 20-year-old Greek male population, were tested. beta-Thalassemia was found with an average incidence of 5.476% and alpha-Thalassemia with an incidence of 0.201%. Hemoglobinopathy Lepore was detected in 51 samples (0.079%) and hemoglobinopathy-S in 352 samples (0.543%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1620378", "endSection": "abstract" } ] }, { "body": "Is exon skipping correlated with exon circularization?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25728652" ], "ideal_answer": [ "Yes. Circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome." ], "exact_answer": "yes", "type": "yesno", "id": "587f5d6492a5b8ad44000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Exon Skipping Is Correlated with Exon Circularization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25728652", "endSection": "title" }, { "offsetInBeginSection": 457, "offsetInEndSection": 632, "text": "We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25728652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Exon Skipping Is Correlated with Exon Circularization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25728652", "endSection": "title" }, { "offsetInBeginSection": 458, "offsetInEndSection": 710, "text": "We find that circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome. Copyright \u00a9 2015 Elsevier Ltd. All rights reserved.Copyright \u00a9 2015 Elsevier Ltd. All rights reserved.\u00a92016 American Association for Cancer Research.\u00a9 The Author 2015", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26424858", "endSection": "abstract" } ] }, { "body": "For what indications is thalidomide currently marketed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12423428", "http://www.ncbi.nlm.nih.gov/pubmed/18034532", "http://www.ncbi.nlm.nih.gov/pubmed/26462773", "http://www.ncbi.nlm.nih.gov/pubmed/26652728", "http://www.ncbi.nlm.nih.gov/pubmed/18050580", "http://www.ncbi.nlm.nih.gov/pubmed/24931258", "http://www.ncbi.nlm.nih.gov/pubmed/10028338", "http://www.ncbi.nlm.nih.gov/pubmed/11809002", "http://www.ncbi.nlm.nih.gov/pubmed/9098920", "http://www.ncbi.nlm.nih.gov/pubmed/24196904", "http://www.ncbi.nlm.nih.gov/pubmed/22650376", "http://www.ncbi.nlm.nih.gov/pubmed/25828060", "http://www.ncbi.nlm.nih.gov/pubmed/15148528", "http://www.ncbi.nlm.nih.gov/pubmed/11717819", "http://www.ncbi.nlm.nih.gov/pubmed/23142220", "http://www.ncbi.nlm.nih.gov/pubmed/11235821", "http://www.ncbi.nlm.nih.gov/pubmed/25573527", "http://www.ncbi.nlm.nih.gov/pubmed/17274497", "http://www.ncbi.nlm.nih.gov/pubmed/8592478", "http://www.ncbi.nlm.nih.gov/pubmed/12190008", "http://www.ncbi.nlm.nih.gov/pubmed/6841082" ], "ideal_answer": [ "Drug repositioning, exemplified by sildenafil and thalidomide, is a promising way to explore alternative indications for existing drugs. THE USE OF A DRUG WITH A TEMPORARY MARKETING AUTHORISATION: Thalidomide is currently available in France for nominative or cohort use with a temporary marketing authorisation (TMA). Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported.We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil.A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13) Currently it includes a group of new drugs (immunosuppressives tacrolimus mycophenolate, thalidomide, biologic therapy, probiotics, neuroinflammation blockers), new treatment techniques (cytaphereses, sequential immunosuppression, immunosuppression with high doses), and finally new indications (chemoprophylaxis). A review of the therapeutic indications for thalidomide in dermatology as well as the mechanisms of action and side-effects of this drug are presented.", "Thalidomide can be used to treat multiple myeloma, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome and possibly Irritable Bowel Syndrome." ], "exact_answer": [ [ "Multiple myeloma" ], [ "polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes", "POEMS" ], [ "Irritable Bowels Syndrome ", "IBS" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056687", "http://www.biosemantics.org/jochem#4018109", "http://www.biosemantics.org/jochem#4017077", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4250023", "http://www.biosemantics.org/jochem#4250023", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013792" ], "type": "list", "id": "58a0da5278275d0c4a000054", "snippets": [ { "offsetInBeginSection": 210, "offsetInEndSection": 456, "text": "In this retrospective study, pharmacy claims were analyzed for those patients with a diagnosis of MM who received thalidomide, lenalidomide, or pomalidomide from a large specialty pharmacy in the US between January 1, 2011, and December 31, 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26652728", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 729, "text": "Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a fatal systemic disorder associated with plasma cell dyscrasia and the overproduction of the vascular endothelial growth factor (VEGF). Recently, the prognosis of POEMS was substantially improved by introduction of therapeutic intervention for myeloma. However, no randomised clinical trial has been performed because of the rarity and severity of the disease.METHODS AND ANALYSIS: The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25573527", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 188, "text": "Thalidomide could relieve clinical symptoms and intestinal mucosal lesions effectively in children with refractory inflammatory bowel disease (IBD) from the pre-clinical study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931258", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 240, "text": "In reactional states of leprosy the use of thalidomide is established.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6841082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The use of thalidomide was never discontinued in Brazil where it is prescribed for leprosy type 2 reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24196904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 24, "text": "New uses of thalidomide.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8592478", "endSection": "title" }, { "offsetInBeginSection": 83, "offsetInEndSection": 695, "text": "Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported.We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil.A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13) per 10,000 births.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828060", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1160, "text": "The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22650376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 580, "text": "To explore the inhibitory effect of thalidomide combined with interferon (IFN) on the human acute myeloid leukemia cell line Kasumi- 1 and its mechanism.The inhibitiory effect of Kasumi- 1 cells by thalidomide, interferon or combination was detected by CCK- 8 method, the apoptosis by flow cytometry, the expression of apoptosis related proteins by Western blot, vascular endothelial growth factor (VEGF) concentration in culture supernatant by ELISA.Thalidomide inhibited the proliferation of Kasumi- 1 in a dose- dependent manner from 50 \u03bcg/ml to 500 \u03bcg/ml with an IC\u2085\u2080 of (451.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26462773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Interferon (INF)-\u03b1 was the maintenance treatment of choice after autologous stem cell transplantation in multiple myeloma in the past, but currently Thalidomide is commonly used", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23142220", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 745, "text": "However, no randomised clinical trial has been performed because of the rarity and severity of the disease.The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome, with an additional 48-week open-label safety study", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25573527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Thalidomide, mainly used for the treatment of leprosy, is a current teratogen in South America, and it is reasonable to assume that at present this situation is affecting many births in underdeveloped countries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9098920", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 676, "text": "Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported.We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil.A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828060", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 768, "text": "A review of the therapeutic indications for thalidomide in dermatology as well as the mechanisms of action and side-effects of this drug are presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12423428", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 675, "text": "Thalidomide first was marketed as a sedative in the 1950s and withdrawn from the market in 1961 following reports of teratogenicity. Later, it was used as an investigational agent for the treatment of Hansen's disease, Kaposi's sarcoma, myelofibrosis, RAUs, and wasting associated with HIV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18050580", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 391, "text": "The drug has since been found effective for several different indications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8592478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Based on present publications we review indications of the therapy of dermatoses with thalidomide as well as possible mechanisms of action and side effects of this drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6841082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Use of thalidomide in dermatological indications.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18034532", "endSection": "title" }, { "offsetInBeginSection": 373, "offsetInEndSection": 507, "text": "Current data demonstrates that thalidomide is clinically promising in multiple myeloma, glioblastoma multiforme and renal cell cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11717819", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 804, "text": "Erythema nodosum leprosum is the only registered indication for the use of thalidomide in the United States of America.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12190008", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 623, "text": "Thalidomide is currently under investigation for the treatment of a wide variety of diseases, including conditions thought to have an inflammatory or immune basis, malignancies and complications of infection with HIV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11235821", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 455, "text": "Gradually, thalidomide was reintroduced for the treatment of a few skin diseases including leprous erythema nodosum, severe mucosal ulcers (e.g., associated with HIV infection or Beh\u00e7et's disease), lymphocytic skin infiltrations, cutaneous lupus erythematosus, and chronic graft-versus-host disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11809002", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 391, "text": "Thalidomide has been used in several cutaneous inflammatory disorders (such as erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17274497", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 312, "text": "This drug was more recently rediscovered as a powerful immunomodulatory and antiinflammatory agent and was approved by the FDA in 1998 for treatment of erythema nodosum leprosum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15148528", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 226, "text": " Since, however, it has been found to be an effective drug in erythema nodosum leprosum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10028338", "endSection": "abstract" } ] }, { "body": "What are reactive metabolites?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25363902", "http://www.ncbi.nlm.nih.gov/pubmed/21769097", "http://www.ncbi.nlm.nih.gov/pubmed/26735163", "http://www.ncbi.nlm.nih.gov/pubmed/25174933", "http://www.ncbi.nlm.nih.gov/pubmed/22681489", "http://www.ncbi.nlm.nih.gov/pubmed/26005795", "http://www.ncbi.nlm.nih.gov/pubmed/27031942", "http://www.ncbi.nlm.nih.gov/pubmed/9614200", "http://www.ncbi.nlm.nih.gov/pubmed/16235238", "http://www.ncbi.nlm.nih.gov/pubmed/23090860", "http://www.ncbi.nlm.nih.gov/pubmed/21148252", "http://www.ncbi.nlm.nih.gov/pubmed/159767", "http://www.ncbi.nlm.nih.gov/pubmed/21504003", "http://www.ncbi.nlm.nih.gov/pubmed/26627130", "http://www.ncbi.nlm.nih.gov/pubmed/25851819", "http://www.ncbi.nlm.nih.gov/pubmed/9144833", "http://www.ncbi.nlm.nih.gov/pubmed/16967439", "http://www.ncbi.nlm.nih.gov/pubmed/25312212", "http://www.ncbi.nlm.nih.gov/pubmed/17145699", "http://www.ncbi.nlm.nih.gov/pubmed/20391594", "http://www.ncbi.nlm.nih.gov/pubmed/21469730", "http://www.ncbi.nlm.nih.gov/pubmed/12093356", "http://www.ncbi.nlm.nih.gov/pubmed/1628536", "http://www.ncbi.nlm.nih.gov/pubmed/18788755", "http://www.ncbi.nlm.nih.gov/pubmed/21083235", "http://www.ncbi.nlm.nih.gov/pubmed/8987247" ], "ideal_answer": [ "Reactive metabolites are generated when a small molecule, commonly a drug or hydrocarbon, is broken down in the body. Reactive metabolites can cause cancer and other diseases as well as hepatoxicty. " ], "type": "summary", "id": "58a3264e60087bc10a00000d", "snippets": [ { "offsetInBeginSection": 1184, "offsetInEndSection": 1683, "text": "The results implicate the cis-enedial reactive metabolite of DIOB was responsible for the observed toxicities. The observed modest depletion of hepatic GSH in DIOB-treated animals suggests the actions of one or more reactive metabolites, and the hepatic injury observed could be due at least in part to reactions of these metabolites with crucial biomolecules. Cytochrome P450 3A enzymes are implicated in DIOB-induced hepatotoxicities by catalyzing the formation of the reactive metabolite of DIOB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25851819", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1470, "text": ". The neurotoxicity of endosulfan and its metabolites is closely related to oxidative damage and antioxidative deficit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25363902", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1462, "text": "Our data from this study strongly indicate that Dic as well as its metabolites could be involved in the hepato-toxic action through inhibition of ATP synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26627130", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 461, "text": "Reactive metabolites can form adducts with trapping reagents, such as glutathione, which makes the reactive metabolites detectable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21469730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "[Reactive metabolites of xenobiotics : their role in the hepatotoxicity of drugs].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/159767", "endSection": "title" }, { "offsetInBeginSection": 127, "offsetInEndSection": 218, "text": "The formation of reactive metabolites has been associated with the observed hepatotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18788755", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Electrochemical oxidation of troglitazone: identification and characterization of the major reactive metabolite in liver microsomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18788755", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "DNA bases attack by reactive metabolites produced during carbon tetrachloride biotransformation and promotion of liver microsomal lipid peroxidation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9144833", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Certain drugs are transformed into reactive metabolites by cytochrome P-450, a hepatic microsomal enzyme. The reactive metabolites covalently bind to hepatocyte macromolecules, thus determining liver lesions. Induction of microsomial enzymes increases the formation of reactive metabolites and exaggerates hepatotoxicity of these drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/159767", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 397, "text": "It is generally accepted that a predominant pathway of drug-induced toxicity is through the generation of reactive metabolites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21148252", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 836, "text": "In addition, the incidence and nature of adverse reactions associated with a given drug is probably determined in large measure by the location of reactive metabolite formation, as well as the chemical reactivity of the reactive metabolite.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1628536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Reactive metabolite-mediated toxicity is frequently limited to the organ where the electrophilic metabolites are generated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22681489", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1438, "text": "While there is a disproportionate number of compounds metabolized to reactive metabolites that are associated with drug-induced hepatotoxicity and serious skin toxicities such as toxic endothelial necrolysis and Steven's Johnson syndrome, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25174933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Central to most hypotheses of the mechanism of idiosyncratic drug-induced blood dyscrasias is the involvement of reactive metabolite", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8987247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Although idiosyncratic adverse drug reactions are rare, they are still a major concern to patient safety. Reactive metabolites are widely accepted as playing a pivotal role in the pathogenesis of idiosyncratic adverse drug reactions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26735163", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 433, "text": "detection and identification of minor reactive metabolites are equally important since the minor metabolites, even though at low levels, may be highly reactive and also play an important role in drug-induced adverse reactions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16235238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Metabolic activation of a drug leading to reactive metabolite(s) that can covalently modify proteins is considered an initial step that may lead to drug-induced organ toxicities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16967439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Reactive metabolites are believed to be responsible for most idiosyncratic drug reactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17145699", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1172, "text": " This review will focus on our current understanding and speculative views on how a reactive metabolite of a drug might ultimately lead to immune-mediated toxicity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12093356", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 259, "text": "he decline in approval of new drugs during the past decade has led to a close analysis of the drug discovery process. One of the main reasons for attrition is preclinical toxicity, frequently attributed to the generation of protein-reactive drug metabolites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Reactive metabolites are estimated to be one of the main reasons behind unexpected drug-induced toxicity, by binding covalently to cell proteins or DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504003", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 210, "text": "rug metabolism can result in the formation of highly reactive metabolites that are known to play a role in toxicity resulting in a significant proportion of attrition during drug development and clinical use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25312212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The formation of reactive metabolites through biotransformation is the suspected cause of many adverse drug reactions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27031942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Drug bioactivation leading to the formation of reactive species capable of covalent binding to proteins represents an important cause of drug-induced toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20391594", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 338, "text": "The traditional view of these reactive oxygen metabolites is one of oxidative stress and damage that leads to decline of tissue and organ systems in aging and disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21769097", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 238, "text": " A number of withdrawn drugs are known to undergo bioactivation by a range of drug metabolizing enzymes to chemically reactive metabolites that bind covalently to protein and DNA resulting in organ toxicity and carcinogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26005795", "endSection": "abstract" } ] }, { "body": "What is the \"wearing-off\" phenomenon in levodopa-treated patients with Parkinson's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25616444", "http://www.ncbi.nlm.nih.gov/pubmed/12658373", "http://www.ncbi.nlm.nih.gov/pubmed/15098347", "http://www.ncbi.nlm.nih.gov/pubmed/10654309", "http://www.ncbi.nlm.nih.gov/pubmed/11889758", "http://www.ncbi.nlm.nih.gov/pubmed/25649051", "http://www.ncbi.nlm.nih.gov/pubmed/16381182", "http://www.ncbi.nlm.nih.gov/pubmed/12722172", "http://www.ncbi.nlm.nih.gov/pubmed/3042912", "http://www.ncbi.nlm.nih.gov/pubmed/3579222", "http://www.ncbi.nlm.nih.gov/pubmed/15824341", "http://www.ncbi.nlm.nih.gov/pubmed/26347184", "http://www.ncbi.nlm.nih.gov/pubmed/26101038", "http://www.ncbi.nlm.nih.gov/pubmed/19793544", "http://www.ncbi.nlm.nih.gov/pubmed/21942133", "http://www.ncbi.nlm.nih.gov/pubmed/8024257", "http://www.ncbi.nlm.nih.gov/pubmed/17878397", "http://www.ncbi.nlm.nih.gov/pubmed/2682215", "http://www.ncbi.nlm.nih.gov/pubmed/9339691", "http://www.ncbi.nlm.nih.gov/pubmed/9343116", "http://www.ncbi.nlm.nih.gov/pubmed/25985062", "http://www.ncbi.nlm.nih.gov/pubmed/27942720", "http://www.ncbi.nlm.nih.gov/pubmed/24830331", "http://www.ncbi.nlm.nih.gov/pubmed/14960500", "http://www.ncbi.nlm.nih.gov/pubmed/18922214", "http://www.ncbi.nlm.nih.gov/pubmed/10439935", "http://www.ncbi.nlm.nih.gov/pubmed/8771074", "http://www.ncbi.nlm.nih.gov/pubmed/9591523", "http://www.ncbi.nlm.nih.gov/pubmed/9591522", "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "http://www.ncbi.nlm.nih.gov/pubmed/16805724", "http://www.ncbi.nlm.nih.gov/pubmed/3435068", "http://www.ncbi.nlm.nih.gov/pubmed/9399217", "http://www.ncbi.nlm.nih.gov/pubmed/9203084", "http://www.ncbi.nlm.nih.gov/pubmed/8255478" ], "ideal_answer": [ "Chronic administration of traditional levodopa/dopa decarboxylase inhibitor formulations to Paskinson's Disease patients is associated with the development of complications, such as wearing-off phenomenon. Wearing-off phenomenon is characterized by the predictable emergence of motor symptoms (e.g. rigidity and freezing) and nonmotor PD symptoms (e.g. anxiety and shortness of breath), before the next scheduled dose of medication." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300", "http://www.biosemantics.org/jochem#4222145", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007980", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275540", "http://www.disease-ontology.org/api/metadata/DOID:14330", "http://www.biosemantics.org/jochem#4001922", "http://www.biosemantics.org/jochem#4257430", "http://www.biosemantics.org/jochem#4275540" ], "type": "summary", "id": "589c389278275d0c4a00003e", "snippets": [ { "offsetInBeginSection": 1624, "offsetInEndSection": 1759, "text": "It is unlike the \"wearing-off\" phenomenon that occurs when dopaminergic drug levels decline and responds to dopaminergic rescue drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824341", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 266, "text": "Unfortunately, chronic use of traditional levodopa/dopa decarboxylase inhibitor formulations is associated with the development of complications, such as wearing-off and dyskinesia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16805724", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1227, "text": "One of the first complications observed with levodopa therapy is wearing-off, which can emerge within 1-3 years of initiation of levodopa treatment. Wearing-off is characterized by the predictable emergence of motor and nonmotor PD symptoms before the next scheduled dose of medication. Despite effective treatment options to tackle wearing-off, it remains underrecognized and under treated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17878397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Shortness of breath, a 'wearing-off' symptom in Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 624, "text": "Although levodopa is considered the gold standard for Parkinson's disease therapy, prolonged use of this drug can result in motor complications such as a 'wearing-off' phenomenon. This outcome is seen in a significant number of patients with Parkinson's disease taking levodopa and, in some cases, is observed only a few hours after intake of the last dose of levodopa. Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations. Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1067, "text": "We report here on a patient with Parkinson's disease who was taking levodopa and developed both shortness of breath and hyperventilation during wearing-off periods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1324, "text": "His shortness of breath was determined to be a wearing-off phenomenon and his condition improved with the addition of a catechol-O-methyltransferase inhibitor (entacapone).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 325, "text": "The wearing-off phenomenon in patients with Parkinson's disease (PD) is a complication of prolonged levodopa usage. During this phenomenon, motor symptoms such as rigidity and freezing re-emerge. This is often accompanied by non-motor symptoms, including anxiety, the so-called wearing-off related anxiety (WRA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26101038", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1253, "text": "Patients with wearing-off tended to receive higher L-dopa dosage and endure longer duration of L-dopa treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8255478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9203084", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 624, "text": "Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Although levodopa is considered the gold standard for Parkinson's disease therapy, prolonged use of this drug can result in motor complications such as a 'wearing-off' phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "More than 50% of patients with Parkinsons disease develop motor response fluctuations (the wearing off\" phenomenon) after more than five years of levodopa therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9591522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "More than 50% of patients with Parkinsons disease develop motor response fluctuations (the \"wearing off\" phenomenon) after more than five years of levodopa therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9343116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The wearing-off phenomenon in patients with Parkinsons disease (PD) is a complication of prolonged levodopa usage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26101038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Short-term effect of a single levodopa dose on micturition disturbance in Parkinsons disease patients with the wearing-off phenomenon", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12722172", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "To evaluate the effectiveness of entacapone in the management of levodopa wearing-off in Parkinsons disease (PD) in a naturalistic, real-life setting.This prospective, open-label, observational study included patients with idiopathic PD. Patients were eligible for inclusion if they had been taking 3-5 doses of levodopa per day for \u22652 months and had shown signs of levodopa wearing-off for \u22651 month", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18922214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "The duration of clinical control of motor symptoms of Parkinson disease (PD) treated with levodopa/carbidopa preparations eventually starts to shorten, a phenomenon known as end-of-dose \"wearing off.\" The involvement of core nonmotor symptoms of \"wearing off\" (depressed mood, pain/aching, anxiety, and cloudy/slowed thinking) is not well understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Efficacy and tolerability of entacapone in patients with Parkinsons disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12658373", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "The efficacy and tolerability of entacapone was investigated in a randomized, double-blind, placebo-controlled, 3-month study of 162 patients with Parkinsons disease (PD) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12658373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinsons disease patients with wearing-off", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26347184", "endSection": "title" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1592, "text": "We conclude that tolcapone as an adjunct offers promise for the relief of the \"wearing-off \" phenomenon in levodopa-treated parkinsonian patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9591523", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1591, "text": "We conclude that tolcapone as an adjunct offers promise for the relief of the \"wearing-off\" phenomenon in levodopa-treated parkinsonian patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9339691", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 650, "text": "Our data also support the involvement of postsynaptic dopamine receptor mechanisms in the wearing-off phenomenon seen in levodopa-treated parkinsonian patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8771074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Short-term effect of a single levodopa dose on micturition disturbance in Parkinson's disease patients with the wearing-off phenomenon.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12722172", "endSection": "title" }, { "offsetInBeginSection": 1629, "offsetInEndSection": 1764, "text": "It is unlike the \"wearing-off\" phenomenon that occurs when dopaminergic drug levels decline and responds to dopaminergic rescue drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "More than 50% of patients with Parkinson's disease develop motor response fluctuations (the 'wearing off\" phenomenon) after more than five years of levodopa therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9591522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose \"wearing-off\" phenomenon has been controlled with more frequent levodopa dosage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9399217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "More than 50% of patients with Parkinson's disease develop motor response fluctuations (the \"wearing off\" phenomenon) after more than five years of levodopa therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9343116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "To evaluate the role of the practicing pharmacist in the identification and current treatment of the levodopa wearing-off phenomenon experienced by patients with Parkinson's disease (PD) who are receiving chronic levodopa therapy.Literature retrieval was accessed through MEDLINE (1967-June 2007) using the terms levodopa, wearing-off, and Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17878397", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 611, "text": "This study investigated the effects of OPC in comparison with placebo on levodopa pharmacokinetics, tolerability and safety, COMT activity and motor response to levodopa in Parkinson's disease (PD) patients with motor fluctuations.This was a randomized, multicentre, double-blind and placebo-controlled study in four parallel groups of PD patients treated with standard-release 100/25 mg levodopa/carbidopa or levodopa/benserazide and with motor fluctuations (wearing-OFF phenomenon).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25649051", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 624, "text": "Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations. Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 624, "text": "This outcome is seen in a significant number of patients with Parkinson's disease taking levodopa and, in some cases, is observed only a few hours after intake of the last dose of levodopa. Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations. Although infrequent, shortness of breath is an important non-motor wearing-off symptom experienced by patients with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 487, "text": "Although levodopa is considered the gold standard for Parkinson's disease therapy, prolonged use of this drug can result in motor complications such as a 'wearing-off' phenomenon. This outcome is seen in a significant number of patients with Parkinson's disease taking levodopa and, in some cases, is observed only a few hours after intake of the last dose of levodopa. Patients experiencing the wearing-off period may present with sensory, autonomic, psychiatric and motor fluctuations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715385", "endSection": "abstract" }, { "offsetInBeginSection": 1230, "offsetInEndSection": 1356, "text": "It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9203084", "endSection": "abstract" }, { "offsetInBeginSection": 1230, "offsetInEndSection": 1357, "text": "It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9203084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Levodopa-treated Parkinson's disease is often complicated by the occurrence of motor fluctuations, which can be predictable ('wearing-off') or unpredictable ('on-off').", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14960500", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 659, "text": "She was treated with 400 mg/day of levodopa-carbidopa, which improved her symptoms, however, she developed wearing off phenomenon 3 years after the initiation of levodopa treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10654309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "[Benefit of L-DOPA-without-DCI (decarboxylase inhibitor) therapy on wearing-off phenomenon in advanced stages of Parkinson's disease patients].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11889758", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "To evaluate the role of the practicing pharmacist in the identification and current treatment of the levodopa wearing-off phenomenon experienced by patients with Parkinson's disease (PD) who are receiving chronic levodopa therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17878397", "endSection": "abstract" }, { "offsetInBeginSection": 1779, "offsetInEndSection": 1995, "text": "However, once the decision to initiate levodopa therapy has been made, studies generally support the use of entacapone as an adjunct to levodopa in patients with Parkinson's disease and the 'wearing off' phenomenon..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10439935", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1623, "text": "These results suggest that wearing-off phenomenon may arise as a consequence of the degeneration of dopamine terminals due to natural disease progression with a resultant inability to buffer variations in levodopa availability; on-off phenomenon, may reflect additional postsynaptic dopamine receptor dysregulation, possibly in response to the resultant, nonphysiologic fluctuations in synaptic dopamine..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3042912", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 988, "text": "Conversion from oral to intravenous levodopa treatment immediately stabilized plasma levodopa levels in both the wearing-off and on-off groups; motor variability also decreased, especially in those with wearing-off phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3042912", "endSection": "abstract" } ] }, { "body": "What are prions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26297259", "http://www.ncbi.nlm.nih.gov/pubmed/27833227", "http://www.ncbi.nlm.nih.gov/pubmed/22363733", "http://www.ncbi.nlm.nih.gov/pubmed/25645281", "http://www.ncbi.nlm.nih.gov/pubmed/27293325", "http://www.ncbi.nlm.nih.gov/pubmed/24390581" ], "ideal_answer": [ "Prion diseases are protein conformation disorders and neither caused by viroid or virus but is a transmissible particle labeled a prion by Pruisner. Normal prion protein becomes infectious by a different folding, but the triggers are not known. ", "A prion is an infectious agent composed entirely of protein and is responsible for a number of neurodegenerative diseases. Prions are self-propagating infectious protein isoforms. " ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011328", "http://www.disease-ontology.org/api/metadata/DOID:649", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017096", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000072002" ], "type": "summary", "id": "58a0f95c78275d0c4a000055", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 259, "text": "Prion diseases are protein conformation disorders and neither caused by viroid or virus but is a transmissible particle labeled a prion by Pruisner. Normal prion protein becomes infectious by a different folding, but the triggers are not known. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "Prions are proteins most commonly associated with fatal neurodegenerative diseases in mammals but are also responsible for a number of harmless heritable phenotypes in yeast. These states arise when a misfolded form of a protein appears and, rather than be removed by cellular quality control mechanisms, persists. The misfolded prion protein forms aggregates and is capable of converting normally folded protein to the misfolded state through direct interaction between the two forms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26297259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterized by the aggregation and deposition of the misfolded prion protein in the brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27293325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Several neurodegenerative diseases such as transmissible spongiform encephalopathies, Alzheimer's and Parkinson's diseases are caused by the conversion of cellular proteins to a pathogenic conformer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25645281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Prions are self-propagating infectious protein isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24390581", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Prions are units of propagation of an altered state of a protein or proteins; prions can propagate from organism to organism, through cooption of other protein copies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22363733", "endSection": "abstract" } ] }, { "body": "Does Vitamin D induce autophagy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27915989", "http://www.ncbi.nlm.nih.gov/pubmed/27174720", "http://www.ncbi.nlm.nih.gov/pubmed/27430408", "http://www.ncbi.nlm.nih.gov/pubmed/26562100" ], "ideal_answer": [ "Yes, vitamin D induces autophagy." ], "exact_answer": "yes", "type": "yesno", "id": "58a957a8cc344ae31e000001", "snippets": [ { "offsetInBeginSection": 1441, "offsetInEndSection": 1503, "text": " 1,25(OH)2D treatment was accompanied by autophagy activation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26562100", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 134, "text": "Autophagy signaling pathway was regulated by vitamin D3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27174720", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1474, "text": "vitamin D induces autophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27430408", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 923, "text": "Vitamin D shows promise for the prevention and amelioration of pathologic responses in IBD, an effect that is mediated, at least in part, by the induction and modulation of autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27915989", "endSection": "abstract" } ] }, { "body": "What is sQTLseekeR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25140736" ], "ideal_answer": [ "sQTLseekeR is an R package for the identification of genetic variants associated with alternative splicing. It is based on a statistical framework that uses a distance-based approach to compute the variability of splicing ratios across observations, and a non-parametric analogue to multivariate analysis of variance." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398", "http://amigo.geneontology.org/amigo/term/GO:0000380" ], "type": "summary", "id": "5883868b2305cd7e21000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Identification of genetic variants associated with alternative splicing using sQTLseekeR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25140736", "endSection": "title" }, { "offsetInBeginSection": 397, "offsetInEndSection": 1107, "text": "We develop a statistical framework that uses a distance-based approach to compute the variability of splicing ratios across observations, and a non-parametric analogue to multivariate analysis of variance. We implement this approach in the R package sQTLseekeR and use it to analyze RNA-Seq data from the Geuvadis project in 465 individuals. We identify hundreds of single nucleotide polymorphisms (SNPs) as splicing QTLs (sQTLs), including some falling in genome-wide association study SNPs. By developing the appropriate metrics, we show that sQTLseekeR compares favorably with existing methods that rely on univariate approaches, predicting variants that behave as expected from mutations affecting splicing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25140736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Identification of genetic variants associated with alternative splicing using sQTLseekeR", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25140736", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Identification of genetic variants associated with alternative splicing using sQTLseekeR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25140736", "endSection": "title" } ] }, { "body": "What is Creutzfeldt-Jakob Disease (CJD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21303352", "http://www.ncbi.nlm.nih.gov/pubmed/26840797", "http://www.ncbi.nlm.nih.gov/pubmed/22930754", "http://www.ncbi.nlm.nih.gov/pubmed/26454226", "http://www.ncbi.nlm.nih.gov/pubmed/16023527", "http://www.ncbi.nlm.nih.gov/pubmed/9660576", "http://www.ncbi.nlm.nih.gov/pubmed/26840342", "http://www.ncbi.nlm.nih.gov/pubmed/11115241", "http://www.ncbi.nlm.nih.gov/pubmed/19702572", "http://www.ncbi.nlm.nih.gov/pubmed/26646926", "http://www.ncbi.nlm.nih.gov/pubmed/12811992", "http://www.ncbi.nlm.nih.gov/pubmed/25552850", "http://www.ncbi.nlm.nih.gov/pubmed/27665282", "http://www.ncbi.nlm.nih.gov/pubmed/1777133" ], "ideal_answer": [ "Creutzfeldt-Jakob disease (CJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of CJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc).", "Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)", "Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11949", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007562" ], "type": "summary", "id": "58a3423e60087bc10a000019", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 148, "text": "Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26454226", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 201, "text": "Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840342", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 369, "text": "The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Creutzfeldt-Jakob disease (CJD) is a progressive, fatal, neurodegenerative disease classified under transmissible spongiform encephalopathies (TSE) or prion diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25552850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22930754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Creutzfeldt-Jakob disease (CJD) is a rare, degenerative and fatal brain disease that appears to be caused by an abnormal form of a protein called a prion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19702572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Creutzfeldt-Jakob disease (CJD) is presumably caused by a slow infectious pathogen or prion. The principal clinical features of Creutzfeldt-Jakob disease are dementia, pyramidal and extrapyramidal symptoms and signs, cerebellar dysfunction, and myoclonus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1777133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, neurodegenerative disorder causing dramatic neuromuscular symptoms, profound dementia, and death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12811992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16023527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a rapid disease course and a mortality rate of 100%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26646926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27665282", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 318, "text": "Creutzfeldt-Jakob disease is a rare neurodegenerative disease that belongs to the group of human spongiform encephalopathies and usually affects elderly people.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11115241", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 88, "text": "Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9660576", "endSection": "abstract" } ] }, { "body": "Describe what is athelia syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24872738", "http://www.ncbi.nlm.nih.gov/pubmed/15950955", "http://www.ncbi.nlm.nih.gov/pubmed/24781087" ], "ideal_answer": [ "Athelia is a very rare entity that is defined by the absence of the nipple-areola complex." ], "type": "summary", "id": "5895b9ae7d9090f35300000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Athelia is a very rare entity that is defined by the absence of the nipple-areola complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24781087", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 737, "text": "Absence of the nipple, areola (athelia), or the breast tissue (amastia) is less frequent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24872738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The absence of nipple-areola complex is a rare entity and is always associated with other anomalies. This paper described a case of bilateral athelia without other alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15950955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 599, "text": "Athelia is a very rare entity that is defined by the absence of the nipple-areola complex. It can affect either sex and is mostly part of syndromes including other congenital or ectodermal anomalies, such as limb-mammary syndrome, scalp-ear-nipple syndrome, or ectodermal dysplasias. Here, we report on three children from two branches of an extended consanguineous Israeli Arab family, a girl and two boys, who presented with a spectrum of nipple anomalies ranging from unilateral hypothelia to bilateral athelia but no other consistently associated anomalies except a characteristic eyebrow shape.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24781087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Athelia is a very rare entity that is defined by the absence of the nipple-areola complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24781087", "endSection": "abstract" } ] }, { "body": "Is RASA2 involved in melanoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26502337" ], "ideal_answer": [ "Yes. Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in \u226530% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/RASA2_RAT", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.uniprot.org/uniprot/RASA2_HUMAN", "http://www.uniprot.org/uniprot/RASA2_MOUSE" ], "type": "yesno", "id": "5896399978275d0c4a00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in \u226530% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26502337", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26502337", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 462, "text": "These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26502337", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 244, "text": "Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26502337", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26502337", "endSection": "abstract" } ] }, { "body": "What is BioCreative?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18629295", "http://www.ncbi.nlm.nih.gov/pubmed/18834491", "http://www.ncbi.nlm.nih.gov/pubmed/22151647", "http://www.ncbi.nlm.nih.gov/pubmed/23327936", "http://www.ncbi.nlm.nih.gov/pubmed/18834496", "http://www.ncbi.nlm.nih.gov/pubmed/15960842", "http://www.ncbi.nlm.nih.gov/pubmed/16504116", "http://www.ncbi.nlm.nih.gov/pubmed/23160416", "http://www.ncbi.nlm.nih.gov/pubmed/27589962", "http://www.ncbi.nlm.nih.gov/pubmed/22151968", "http://www.ncbi.nlm.nih.gov/pubmed/22438567", "http://www.ncbi.nlm.nih.gov/pubmed/18834487", "http://www.ncbi.nlm.nih.gov/pubmed/22151178", "http://www.ncbi.nlm.nih.gov/pubmed/15960829", "http://www.ncbi.nlm.nih.gov/pubmed/20498514", "http://www.ncbi.nlm.nih.gov/pubmed/15960843", "http://www.ncbi.nlm.nih.gov/pubmed/15960821" ], "ideal_answer": [ "A community wide effort to evaluate biomedical information extraction and text mining." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063369" ], "type": "summary", "id": "589c8ef878275d0c4a000042", "snippets": [ { "offsetInBeginSection": 142, "offsetInEndSection": 272, "text": " two biomedical named entity recognition (NER) comparative evaluations that have been held to date, namely BioCreative and Coling ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18629295", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 807, "text": "The BioCreative II.5 community challenge addressed these tasks in a competition-style assessment to evaluate and compare different methodologies, to make aware of the increasing accuracy of automated methods, and to guide future implementations. In this paper, we present our approaches for protein-named entity recognition,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20498514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "In task 1A of the BioCreAtIvE evaluation, systems had to be devised that recognize words and phrases forming gene or protein names in natural language sentences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960843", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 417, "text": "BioCreAtIvE, a competition for automated gene/protein name recognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "An overview of the BioCreative 2012 Workshop Track III: interactive text mining task.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23327936", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Biocuration workflows and text mining: overview of the BioCreative 2012 Workshop Track II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23160416", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Evaluation of text-mining systems for biology: overview of the Second BioCreative community challenge.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18834487", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "How to link ontologies and protein-protein interactions to literature: text-mining approaches and the BioCreative experience.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438567", "endSection": "title" }, { "offsetInBeginSection": 563, "offsetInEndSection": 713, "text": "The 2006 BioCreative competition was aimed at evaluating text-mining procedures in comparison with manual annotation of protein-protein interactions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18834496", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 927, "text": "RESULTS: The Biocreative 2010 competition addressed three tasks: gene normalization, article classification and interaction method identification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22151178", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1222, "text": "BioCreAtIvE task 2 was an experiment to test if automatically derived classification using information retrieval and extraction could assist expert biologists in the annotation of the GO vocabulary to the proteins in the UniProt Knowledgebase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960829", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 465, "text": "To this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative II.5 in 2009. Each of these workshops involved humanly annotated test data for several basic tasks in text mining applied to the biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22151647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "BACKGROUND: The overall goal of the BioCreative Workshops is to promote the development of text mining and text processing tools which are useful to the communities of researchers and database curators in the biological sciences. To this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative II.5 in 2009.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22151647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 465, "text": "BACKGROUND: The overall goal of the BioCreative Workshops is to promote the development of text mining and text processing tools which are useful to the communities of researchers and database curators in the biological sciences. To this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative II.5 in 2009. Each of these workshops involved humanly annotated test data for several basic tasks in text mining applied to the biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22151647", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 650, "text": "To this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative II.5 in 2009. Each of these workshops involved humanly annotated test data for several basic tasks in text mining applied to the biomedical literature. Participants in the workshops were invited to compete in the tasks by constructing software systems to perform the tasks automatically and were given scores based on their performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22151647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Overview of BioCreAtIvE: critical assessment of information extraction for biology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15960821", "endSection": "title" } ] }, { "body": "What is Contrave prescribed for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20673995", "http://www.ncbi.nlm.nih.gov/pubmed/22313529", "http://www.ncbi.nlm.nih.gov/pubmed/26679384", "http://www.ncbi.nlm.nih.gov/pubmed/26105116", "http://www.ncbi.nlm.nih.gov/pubmed/25258511", "http://www.ncbi.nlm.nih.gov/pubmed/26222044", "http://www.ncbi.nlm.nih.gov/pubmed/26957883", "http://www.ncbi.nlm.nih.gov/pubmed/20509712", "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "http://www.ncbi.nlm.nih.gov/pubmed/21951371", "http://www.ncbi.nlm.nih.gov/pubmed/26648466", "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "http://www.ncbi.nlm.nih.gov/pubmed/23408728" ], "ideal_answer": [ "Contrave(?) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity", "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity", "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity." ], "exact_answer": [ "Obesity" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009271", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055553", "http://www.biosemantics.org/jochem#4276121", "http://www.biosemantics.org/jochem#4249647", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016642" ], "type": "factoid", "id": "58a32edd60087bc10a000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679384", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 984, "text": "Assuming that the results of the Contrave phase III clinical program reaffirm the efficacy and safety of the drug combination, this agent could be approved and launched to become a market leader in the anti-obesity therapeutic arena.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 924, "text": "Current antiobesity medications and pharmacological strategies will be reviewed.Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 698, "text": "The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants.Men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20673995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Contrave, under development by Orexigen Therapeutics Inc for the potential treatment of obesity, is an oral, sustained-release combination of the dopamine and norepinephrine reuptake antagonist bupropion and the opioid antagonist naltrexone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Naltrexone/bupropion: Contrave(R); naltrexone SR/bupropion SR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20509712", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Naltrexone/bupropion ER (Contrave): newly approved treatment option for chronic weight management in obese adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26957883", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1110, "text": " The use of synergies of anti-obesity drugs with different mechanisms of action is an effective approach for developing new combined pharmaceutical compositions (Contrave\u00ae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26648466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 448, "text": "Oral naltrexone extended-release/bupropion extended-release (naltrexone ER/bupropion ER; Contrave(\u00ae), Mysimba(\u2122)) is available as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial body mass index (BMI) of \u2265 30 kg/m(2) (i.e. obese) or a BMI of \u2265 27 kg/m(2) (i.e. overweight) in the presence of at least one bodyweight-related comorbidity, such as type 2 diabetes mellitus, hypertension or dyslipidaemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26105116", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 370, "text": "naltrexone/bupropion (NB32 or Contrave\u00ae)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222044", "endSection": "abstract" } ] }, { "body": "Which is the chromosome area that the human gene coding for the dopamine transporter (DAT1) is located to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16222334", "http://www.ncbi.nlm.nih.gov/pubmed/1478653", "http://www.ncbi.nlm.nih.gov/pubmed/19779799", "http://www.ncbi.nlm.nih.gov/pubmed/16861140", "http://www.ncbi.nlm.nih.gov/pubmed/17579611" ], "ideal_answer": [ "The gene encoding DAT1 consists of 15 exons spanning 60 kb and is located on chromosome 5p15.3." ], "exact_answer": [ "5p15.3" ], "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275128", "http://www.biosemantics.org/jochem#4275128", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004298", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050483" ], "type": "factoid", "id": "58a2ced760087bc10a000004", "snippets": [ { "offsetInBeginSection": 171, "offsetInEndSection": 252, "text": "The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19779799", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1094, "text": "The locus of the solute carrier 6A3 (SLC6A3; dopamine transporter 1; DAT1) localizes to 5p15.33; the gene has repeatedly been implicated in the etiology of ADHD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16222334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "In 29 adults with attention deficit hyperactivity disorder (ADHD) striatal dopamine transporter (DAT) availability was assessed by [(99m)Tc]TRODAT-1 SPECT and correlated with 3' VNTR polymorphism of the DAT gene on chromosome 5p15.3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16861140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1478653", "endSection": "title" }, { "offsetInBeginSection": 171, "offsetInEndSection": 253, "text": "The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19779799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "The dopamine transporter (DAT1) is a membrane spanning protein that binds the neurotransmitter dopamine and performs re-uptake of dopamine from the synapse into a neuron. The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32. Several studies have investigated the possible associations between variants in DAT1 gene and psychiatric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19779799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "The dopamine transporter (DAT1) is a membrane spanning protein that binds the neurotransmitter dopamine and performs re-uptake of dopamine from the synapse into a neuron. The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19779799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1478653", "endSection": "title" } ] }, { "body": "What type of mutation is causing the industrial melanism phenotype in peppered moths?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27251284", "http://www.ncbi.nlm.nih.gov/pubmed/12298233", "http://www.ncbi.nlm.nih.gov/pubmed/12140267" ], "ideal_answer": [ "The mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex." ], "exact_answer": [ "transposable element insertion" ], "type": "factoid", "id": "58a877cf38c171fb5b000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The industrial melanism mutation in British peppered moths is a transposable element.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27251284", "endSection": "title" }, { "offsetInBeginSection": 685, "offsetInEndSection": 879, "text": "Here we show that the mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27251284", "endSection": "abstract" } ] }, { "body": "What gene is mutated in Huntington's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25993131", "http://www.ncbi.nlm.nih.gov/pubmed/1839672", "http://www.ncbi.nlm.nih.gov/pubmed/25254119", "http://www.ncbi.nlm.nih.gov/pubmed/26863614", "http://www.ncbi.nlm.nih.gov/pubmed/18651325", "http://www.ncbi.nlm.nih.gov/pubmed/19059613", "http://www.ncbi.nlm.nih.gov/pubmed/26160070", "http://www.ncbi.nlm.nih.gov/pubmed/16109169", "http://www.ncbi.nlm.nih.gov/pubmed/15651335", "http://www.ncbi.nlm.nih.gov/pubmed/11723754", "http://www.ncbi.nlm.nih.gov/pubmed/19816846", "http://www.ncbi.nlm.nih.gov/pubmed/26079385", "http://www.ncbi.nlm.nih.gov/pubmed/12805114", "http://www.ncbi.nlm.nih.gov/pubmed/9392570", "http://www.ncbi.nlm.nih.gov/pubmed/25931812", "http://www.ncbi.nlm.nih.gov/pubmed/12523115", "http://www.ncbi.nlm.nih.gov/pubmed/16847693", "http://www.ncbi.nlm.nih.gov/pubmed/17941857", "http://www.ncbi.nlm.nih.gov/pubmed/27400454", "http://www.ncbi.nlm.nih.gov/pubmed/26466780", "http://www.ncbi.nlm.nih.gov/pubmed/8985734", "http://www.ncbi.nlm.nih.gov/pubmed/24196395", "http://www.ncbi.nlm.nih.gov/pubmed/11494364" ], "ideal_answer": [ "Huntington disease (HD; OMIM 143100), a progressive neurodegenerative disorder, is caused by an expanded trinucleotide CAG (polyQ) motif in the HTT gene. Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD).", "Huntington disease is a progressive neurodegenerative disorder and is caused by an expanded trinucleotide CAG (polyQ) motif in the HTT gene." ], "exact_answer": [ "HTT or IT-15 gene or HD gene" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1289", "http://www.disease-ontology.org/api/metadata/DOID:12858", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006816" ], "type": "factoid", "id": "58a3428d60087bc10a00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Huntington disease (HD; OMIM 143100), a progressive neurodegenerative disorder, is caused by an expanded trinucleotide CAG (polyQ) motif in the HTT gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25993131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Huntington's disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25931812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26863614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Huntington's disease is an inherited disorder caused by expansion of a CAG trinucleotide repeat in the IT15 gene, which leads to expansion of a polyglutamine tract within the protein called huntingtin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9392570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Huntington disease is a monogenic, autosomal dominant, progressive neurodegenerative disorder caused by a trinucleotide CAG repeat expansion in exon 1 of the huntingtin (HTT) gene; age of onset of clinical symptoms inversely correlates with expanded CAG repeat length", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24196395", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 446, "text": "The causative gene (mutated HTT) is widely expressed outside the CNS and several peripheral signs of disease, including weight loss and increased proinflammatory signalling, are often seen; however, their importance in the pathophysiology of Huntington's disease is not clear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26466780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by a single-gene mutation: a CAG expansion in the huntingtin (HTT) gene that results in production of a mutated protein, mutant HTT, with a polyglutamine tail (polyQ-HTT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26160070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 666, "text": "Huntington's disease is an inherited disorder caused by expansion of a CAG trinucleotide repeat in the IT15 gene, which leads to expansion of a polyglutamine tract within the protein called huntingtin. Despite the characterization of the IT15 gene and the mutation involved in the disease, the normal function of huntingtin and the effects of the mutation on its function and on its neuronal location remain unknown. To study whether mutated huntingtin has the same neuronal distribution and intracellular location as normal huntingtin, we analyzed immunohistochemically both forms of this protein in the brain of 5 controls and 5 patients with Huntington's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9392570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "Huntington's disease is an inherited disorder caused by expansion of a CAG trinucleotide repeat in the IT15 gene, which leads to expansion of a polyglutamine tract within the protein called huntingtin. Despite the characterization of the IT15 gene and the mutation involved in the disease, the normal function of huntingtin and the effects of the mutation on its function and on its neuronal location remain unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9392570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Huntingtons disease (HD) is a hereditary disorder involving the central nervous system. Its effects are devastating, to the affected person as well as his family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1839672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Huntington disease (HD) is a neurodegenerative disorder due to an excessive number of CAG repeats in the IT15 gene on chromosome 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17941857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Huntington disease in subjects from an Israeli Karaite community carrying alleles of intermediate and expanded CAG repeats in the HTT gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19059613", "endSection": "title" }, { "offsetInBeginSection": 79, "offsetInEndSection": 176, "text": "The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25254119", "endSection": "abstract" }, { "offsetInBeginSection": 35, "offsetInEndSection": 124, "text": "Huntington's disease in relation to the number of trinucleotide CAG repeats in IT-15 gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12523115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Huntington's disease (HD) is a neurological condition of progressive course that results from abnormally increased number of CAG repeats within IT-15 gene, coding for huntington.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12523115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Huntington's disease (HD) is a neurodegenerative disorder characterized by the expansion of CAG repeats in exon 1 of the HD gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11494364", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 268, "text": "However, not all patients with an HD phenotype carry the pathological expansion in HTT, and the positive diagnosis rate is poor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27400454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The expansion of a polymorphic CAG repeat in the HD gene encoding huntingtin has been identified as the major cause of Huntington's disease (HD) and determines 42-73% of the variance in the age-at-onset of the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26079385", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 245, "text": "The disorder is caused by mutation in the gene encoding the huntingtin protein (Htt), producing intracellular aggregates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19816846", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 700, "text": "HD is less common in other ethnic groups. Huntington's disease is caused by an expanded trinucleotide CAG repeat in the HD gene on chromosome 4. The gene encodes for the protein huntingtin, with an as yet unknown functio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11723754", "endSection": "abstract" } ] }, { "body": "Which software package is available for the analysis of conserved genomic loci?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26530724" ], "ideal_answer": [ "PHYLUCE is a software package for the analysis of conserved genomic loci. It identifies targeted, enriched loci from the off-target background data; aligns enriched contigs representing conserved loci to one another; and prepare and manipulate these alignments for subsequent phylogenomic inference. PHYLUCE is an efficient and easy-to-install software package that accomplishes these tasks across hundreds of taxa and thousands of enriched loci", "PHYLUCE is a software package for the analysis of conserved genomic loci" ], "exact_answer": [ "PHYLUCE" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012984", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017124" ], "type": "factoid", "id": "587e07023ec846c24f000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "PHYLUCE is a software package for the analysis of conserved genomic loci", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530724", "endSection": "title" }, { "offsetInBeginSection": 199, "offsetInEndSection": 716, "text": "Prior to downstream inference, data from these types of targeted enrichment studies must undergo preprocessing to assemble contigs from sequence data; identify targeted, enriched loci from the off-target background data; align enriched contigs representing conserved loci to one another; and prepare and manipulate these alignments for subsequent phylogenomic inference. PHYLUCE is an efficient and easy-to-install software package that accomplishes these tasks across hundreds of taxa and thousands of enriched loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "PHYLUCE is a software package for the analysis of conserved genomic loci.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530724", "endSection": "title" } ] }, { "body": "Mutation of which gene is implicated in the Christianson syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "http://www.ncbi.nlm.nih.gov/pubmed/18342287", "http://www.ncbi.nlm.nih.gov/pubmed/26421989", "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "http://www.ncbi.nlm.nih.gov/pubmed/25273398", "http://www.ncbi.nlm.nih.gov/pubmed/27142213", "http://www.ncbi.nlm.nih.gov/pubmed/26515654", "http://www.ncbi.nlm.nih.gov/pubmed/27256868", "http://www.ncbi.nlm.nih.gov/pubmed/20949524", "http://www.ncbi.nlm.nih.gov/pubmed/25002837", "http://www.ncbi.nlm.nih.gov/pubmed/27590723", "http://www.ncbi.nlm.nih.gov/pubmed/24839169", "http://www.ncbi.nlm.nih.gov/pubmed/24285247", "http://www.ncbi.nlm.nih.gov/pubmed/24779060", "http://www.ncbi.nlm.nih.gov/pubmed/21964919", "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "http://www.ncbi.nlm.nih.gov/pubmed/22541666" ], "ideal_answer": [ "Christianson syndrome is caused by mutations in SLC9A6 and is characterized by severe intellectual disability, absent speech, microcephaly, ataxia, seizures, and behavioral abnormalities." ], "exact_answer": [ "SLC9A6" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ], "type": "factoid", "id": "5895bc397d9090f35300000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515654", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 434, "text": "CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium)-hydrogen exchanger 6 (NHE6) protein, functional in early recycling endosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "A Christianson syndrome-linked deletion mutation (\u2206(287)ES(288)) in SLC9A6 disrupts recycling endosomal function and elicits neurodegeneration and cell death.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27590723", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "BACKGROUND: Christianson Syndrome, a recently identified X-linked neurodevelopmental disorder, is caused by mutations in the human gene SLC9A6 encoding the recycling endosomal alkali cation/proton exchanger NHE6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27590723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "BACKGROUND: Mutations of SLC9A6 may cause an X-linked clinical syndrome first described by Christianson in 1999 in which affected males exhibited profound intellectual disability, autism, drug-resistant epilepsy, ophthalmoplegia, mild craniofacial dysmorphism, microcephaly, and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26421989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "OBJECTIVE: Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044251", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 583, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia. In a 7-year-old boy with characteristic clinical and neuroimaging features of Christianson syndrome and epileptic encephalopathy with continuous spikes and waves during sleep, we identified a novel splice site mutation (IVS10-1G>A) in SLC9A6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Christianson syndrome (CS) is caused by mutations in SLC9A6 and is characterized by severe intellectual disability, absent speech, microcephaly, ataxia, seizures, and behavioral abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285247", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 481, "text": "We report on two children with CS and confirmed mutations in SLC9A6 focusing on neuroimaging findings and review the available literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Mutations in the SLC9A6 gene cause Christianson syndrome in boys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Novel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "title" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1432, "text": "This patient broadens the spectrum of SLC9A6 mutations and contributes to the clinical delineation of Christianson syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Novel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Mutations in the SLC9A6 gene cause Christianson syndrome in boys. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22541666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 443, "text": "Mutations in SLC9A6 are associated with Christianson syndrome (OMIM 300243), a syndromic form of X-linked mental retardation (XLMR) characterized by microcephaly, severe global developmental delay, ataxia and seizures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1433, "text": "This patient broadens the spectrum of SLC9A6 mutations and contributes to the clinical delineation of Christianson syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 972, "text": "The single-gene disorders include Pitt\u2013Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat\u2013Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779060", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 583, "text": "In a 7-year-old boy with characteristic clinical and neuroimaging features of Christianson syndrome and epileptic encephalopathy with continuous spikes and waves during sleep, we identified a novel splice site mutation (IVS10-1G>A) in SLC9A6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 442, "text": "Mutations in SLC9A6 are associated with Christianson syndrome (OMIM 300243), a syndromic form of X-linked mental retardation (XLMR) characterized by microcephaly, severe global developmental delay, ataxia and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21932316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Christianson Syndrome, a recently identified X-linked neurodevelopmental disorder, is caused by mutations in the human gene SLC9A6 encoding the recycling endosomal alkali cation/proton exchanger NHE6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27590723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27256868", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 433, "text": "CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium)-hydrogen exchanger 6 (NHE6) protein, functional in early recycling endosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515654", "endSection": "abstract" }, { "offsetInBeginSection": 1674, "offsetInEndSection": 2010, "text": "Our studies in heterozygous Slc9a6 KO female mice provide important clues for understanding the likely phenotypic range of Christianson syndrome among females heterozygous for SLC9A6 mutations and might improve diagnostic practice and genetic counseling by helping to characterize this presumably underappreciated patient/carrier group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630051", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515654", "endSection": "title" } ] }, { "body": "What is Eteplirsen (Exondys 51)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27807823", "http://www.ncbi.nlm.nih.gov/pubmed/21540335", "http://www.ncbi.nlm.nih.gov/pubmed/25980936", "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "http://www.ncbi.nlm.nih.gov/pubmed/27936976", "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "http://www.ncbi.nlm.nih.gov/pubmed/23075107" ], "ideal_answer": [ "Eteplirsen (Exondys 51) is an antisense oligonucleotide designed to induce exon 51 skipping that is developed by Sarepta Therapeutics. Intravenous eteplirsen has received accelerated approval from the US FDA for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene amenable to exon 51 skipping.\nBy the method of exon skipping in dystrophin pre-mRNA the reading frame is restored and the internally deleted but functional dystrophin is produced." ], "type": "summary", "id": "58a9d3cd396a458e50000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Eteplirsen (Exondys\u00a051) is an antisense oligonucleotide designed to induce exon 51 skipping that is developed by Sarepta Therapeutics. Intravenous eteplirsen has received accelerated approval from the US FDA for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene amenable to exon 51 skipping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27807823", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 299, "text": "Exon skipping is a therapeutic approach for Duchenne muscular dystrophy (DMD) that has been in development for close to two decades. This approach uses antisense oligonucleotides (AONs) to modulate pre-mRNA splicing of dystrophin transcripts to restore the disrupted DMD reading frame. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27936976", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 571, "text": "By the method of exon skipping in dystrophin pre-mRNA the reading frame is restored and the internally deleted but functional dystrophin is produced. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25980936", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 214, "text": "s, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Restoration of the open reading frame of the DMD gene and dystrophin protein production in Duchenne muscular dystrophy (DMD) can be achieved by exon skipping using antisense oligomers (AOs) targeted to splicing elements. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23075107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 382, "text": "We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "AVI-4658 is a phosphorodiamidate morpholino oligomer (PMO) designed to induce skipping of dystrophin exon 51 and restore its expression in patients with Duchenne muscular dystrophy (DMD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21540335", "endSection": "abstract" } ] }, { "body": "What are the SINEUPs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26259533", "http://www.ncbi.nlm.nih.gov/pubmed/27646849", "http://www.ncbi.nlm.nih.gov/pubmed/26029048", "http://www.ncbi.nlm.nih.gov/pubmed/25883552", "http://www.ncbi.nlm.nih.gov/pubmed/26045368", "http://www.ncbi.nlm.nih.gov/pubmed/27265476" ], "ideal_answer": [ "SINEUPs represent a new class of natural and synthetic antisense long non-coding RNAs that activate translation. These molecules have been named SINEUPs since their function requires the activity of an embedded inverted SINEB2 sequence to UP-regulate translation. Natural SINEUPs suggest that embedded Transposable Elements may represent functional domains in long non-coding RNAs. Synthetic SINEUPs may be designed by targeting the antisense sequence to the mRNA of choice representing the first scalable tool to increase protein synthesis of potentially any gene of interest." ], "type": "summary", "id": "587d3873ae41fa4569000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "SINEUPs: A new class of natural and synthetic antisense long non-coding RNAs that activate translation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259533", "endSection": "title" }, { "offsetInBeginSection": 208, "offsetInEndSection": 828, "text": "In this review, we will detail the discovery of a new functional class of natural and synthetic antisense lncRNAs that stimulate translation of sense mRNAs. These molecules have been named SINEUPs since their function requires the activity of an embedded inverted SINEB2 sequence to UP-regulate translation. Natural SINEUPs suggest that embedded Transposable Elements may represent functional domains in long non-coding RNAs. Synthetic SINEUPs may be designed by targeting the antisense sequence to the mRNA of choice representing the first scalable tool to increase protein synthesis of potentially any gene of interest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "SINEUPs are modular antisense long non-coding RNAs that increase synthesis of target proteins in cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029048", "endSection": "title" }, { "offsetInBeginSection": 1736, "offsetInEndSection": 1973, "text": "In summary, SINEUPs represent the first scalable tool to increase synthesis of proteins of interest. We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029048", "endSection": "abstract" }, { "offsetInBeginSection": 1734, "offsetInEndSection": 1833, "text": "In summary, SINEUPs represent the first scalable tool to increase synthesis of proteins of interest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029048", "endSection": "abstract" }, { "offsetInBeginSection": 1835, "offsetInEndSection": 1971, "text": "We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26029048", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 514, "text": "These molecules have been named SINEUPs since their function requires the activity of an embedded inverted SINEB2 sequence to UP-regulate translation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259533", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 632, "text": "Natural SINEUPs suggest that embedded Transposable Elements may represent functional domains in long non-coding RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259533", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 828, "text": "Synthetic SINEUPs may be designed by targeting the antisense sequence to the mRNA of choice representing the first scalable tool to increase protein synthesis of potentially any gene of interest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259533", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 749, "text": "We have previously identified SINEUPs as a new functional class of natural and synthetic long non-coding RNAs that through the activity of an inverted SINEB2 element are able to promote translation of partially overlapping sense coding mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26045368", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 894, "text": "Here we show that by taking advantage of their modular structure, synthetic SINEUPs can be designed to increase production of secreted proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26045368", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1355, "text": "These results lead us to propose synthetic SINEUPs as new versatile tools to optimize production of secreted proteins in manufacturing pipelines and natural SINEUPs as new regulatory RNAs in the secretory pathways. Copyright \u00a9 2015 Elsevier B.V. All rights reserved.4,300 SUMOylation sites in>1,600 proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218447", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 880, "text": "We quantitatively studied SUMOylation dynamics in response to SUMO protease inhibition, proteasome inhibition and heat shock. Many SUMOylated lysines have previously been reported to be ubiquitinated, acetylated or methylated, thus indicating cross-talk between SUMO and other post-translational modifications. We identified 70 phosphorylation and four acetylation events in proximity to SUMOylation sites, and we provide evidence for acetylation-dependent SUMOylation of endogenous histone H3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218447", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 589, "text": "Sumoylation is a post-translational modification shown to play a role in diverse biological processes. Here, we demonstrate that sumoylation is essential for proper heterochromatin function in Drosophila through modification of SU(VAR)3-7. Indeed, SU(VAR)3-7 is sumoylated at lysine K839; this modification is required for localization of SU(VAR)3-7 at pericentric heterochromatin, chromosome 4, and telomeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20299342", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 418, "text": "Sumoylation is a post-translational modification shown to play a role in diverse biological processes. Here, we demonstrate that sumoylation is essential for proper heterochromatin function in Drosophila through modification of SU(VAR)3-7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20299342", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 952, "text": "Our results suggest a new level of regulation of Sall activity in vivo during animal development through post-translational modification by sumoylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20562097", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "BACKGROUND: Small Ubiquitin-like MOdifier protein (SUMO) is a key regulator of nuclear functions but little is known regarding the role of the post-translational modification sumoylation outside of the nucleus, particularly in the Central Nervous System (CNS).METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the expression levels of SUMO-modified substrates as well as the components of the sumoylation machinery are temporally and spatially regulated in the developing rat brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "SUMOylation in Giardia lamblia: A Conserved Post-Translational Modification in One of the Earliest Divergent Eukaryotes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24970140", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Identification of a novel post-translational modification in Plasmodium falciparum: protein sumoylation in different cellular compartments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18547337", "endSection": "title" }, { "offsetInBeginSection": 659, "offsetInEndSection": 899, "text": "More recently, Akt has been identified as a substrate for many different post-translational modifications, including not only phosphorylation of other residues, but also acetylation, glycosylation, oxidation, ubiquitination and SUMOylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25997832", "endSection": "abstract" } ] }, { "body": "What is the Shelterin complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27814571", "http://www.ncbi.nlm.nih.gov/pubmed/26598048", "http://www.ncbi.nlm.nih.gov/pubmed/26748096", "http://www.ncbi.nlm.nih.gov/pubmed/26921407", "http://www.ncbi.nlm.nih.gov/pubmed/27135879", "http://www.ncbi.nlm.nih.gov/pubmed/26871633", "http://www.ncbi.nlm.nih.gov/pubmed/26119943" ], "ideal_answer": [ "Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA. Alterations or removal of individual shelterin components would lead to telomere uncapping and telomere dysfunction, resulting in cellular senescence and transformation to a malignant state." ], "type": "summary", "id": "58a9cd03396a458e50000003", "snippets": [ { "offsetInBeginSection": 424, "offsetInEndSection": 764, "text": "Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA. Alterations or removal of individual shelterin components would lead to telomere uncapping and telomere dysfunction, resulting in cellular senescence and transformation to a malignant state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27814571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Telomeres interact with numerous proteins, including components of the shelterin complex, whose alteration, similarly to proliferation-induced telomere shortening, initiates cellular senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26119943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Telomere repeat binding factor TRF2 is a member of shelterin complex with an important role in protecting and stabilizing chromosomal ends.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598048", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 236, "text": "In human, the shelterin complex binds TTAGGG DNA repeats and provides capping to chromosome ends.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26748096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26871633", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Telomeres, repetitive DNA sequences at chromosome ends, are shielded against the DNA damage response (DDR) by the shelterin complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26871633", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 357, "text": "Telomeres need to be protected by the shelterin complex to avoid junctions occurring between chromosomes while failing topoisomerases or clustered DNA damage processing may produce double-strand breaks, thus requiring swift repair to avoid cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921407", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 274, "text": "A multiprotein complex known as shelterin prevents recognition of telomeric sequences as sites of DNA damage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27135879", "endSection": "abstract" } ] }, { "body": "What disease is the drug aducanumab targeting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27025652", "http://www.ncbi.nlm.nih.gov/pubmed/27810931", "http://www.ncbi.nlm.nih.gov/pubmed/27582220", "http://www.ncbi.nlm.nih.gov/pubmed/27251914" ], "ideal_answer": [ "Aducanumab is an anti-A\u03b2 antibody being developed for the treatment of Alzheimer's disease (AD)." ], "exact_answer": [ "Alzheimer's disease" ], "type": "factoid", "id": "58a95c711978bbde22000001", "snippets": [ { "offsetInBeginSection": 1462, "offsetInEndSection": 1658, "text": " Most importantly, recent trials of three different A\u03b2 antibodies (solanezumab, crenezumab, and aducanumab) have suggested a slowing of cognitive decline in post hoc analyses of mild AD subjects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27025652", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 999, "text": "ecent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27251914", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1520, "text": "Aducanumab is an anti-A\u03b2 antibody being developed for the treatment of AD, and interim analyses of a phase 1b clinical trial have suggested potential beneficial effects on the amyloid pathology and the cognitive status in patients treated with aducanumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "The antibody aducanumab reduces A\u03b2 plaques in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27582220", "endSection": "title" } ] }, { "body": "Which human syndromes have been detected with Fluorescence in situ hybridization (FISH)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26355708", "http://www.ncbi.nlm.nih.gov/pubmed/16857771", "http://www.ncbi.nlm.nih.gov/pubmed/16351727", "http://www.ncbi.nlm.nih.gov/pubmed/12505257", "http://www.ncbi.nlm.nih.gov/pubmed/26066831", "http://www.ncbi.nlm.nih.gov/pubmed/11424143", "http://www.ncbi.nlm.nih.gov/pubmed/22749034", "http://www.ncbi.nlm.nih.gov/pubmed/9806578", "http://www.ncbi.nlm.nih.gov/pubmed/14669212", "http://www.ncbi.nlm.nih.gov/pubmed/10699172", "http://www.ncbi.nlm.nih.gov/pubmed/16222476", "http://www.ncbi.nlm.nih.gov/pubmed/26829723", "http://www.ncbi.nlm.nih.gov/pubmed/24056568", "http://www.ncbi.nlm.nih.gov/pubmed/17867985", "http://www.ncbi.nlm.nih.gov/pubmed/9763574", "http://www.ncbi.nlm.nih.gov/pubmed/25754580", "http://www.ncbi.nlm.nih.gov/pubmed/11876976", "http://www.ncbi.nlm.nih.gov/pubmed/10493892", "http://www.ncbi.nlm.nih.gov/pubmed/1394103", "http://www.ncbi.nlm.nih.gov/pubmed/1897521", "http://www.ncbi.nlm.nih.gov/pubmed/11769675", "http://www.ncbi.nlm.nih.gov/pubmed/27134897", "http://www.ncbi.nlm.nih.gov/pubmed/17394204", "http://www.ncbi.nlm.nih.gov/pubmed/12513811", "http://www.ncbi.nlm.nih.gov/pubmed/8634784", "http://www.ncbi.nlm.nih.gov/pubmed/15287942", "http://www.ncbi.nlm.nih.gov/pubmed/15949578", "http://www.ncbi.nlm.nih.gov/pubmed/18991056", "http://www.ncbi.nlm.nih.gov/pubmed/8260718", "http://www.ncbi.nlm.nih.gov/pubmed/20064152", "http://www.ncbi.nlm.nih.gov/pubmed/12744739", "http://www.ncbi.nlm.nih.gov/pubmed/11484160", "http://www.ncbi.nlm.nih.gov/pubmed/7627929", "http://www.ncbi.nlm.nih.gov/pubmed/17631477", "http://www.ncbi.nlm.nih.gov/pubmed/8152255", "http://www.ncbi.nlm.nih.gov/pubmed/26509426", "http://www.ncbi.nlm.nih.gov/pubmed/8795688", "http://www.ncbi.nlm.nih.gov/pubmed/9951451", "http://www.ncbi.nlm.nih.gov/pubmed/10464634", "http://www.ncbi.nlm.nih.gov/pubmed/18356781", "http://www.ncbi.nlm.nih.gov/pubmed/12673589", "http://www.ncbi.nlm.nih.gov/pubmed/9359505", "http://www.ncbi.nlm.nih.gov/pubmed/25011965", "http://www.ncbi.nlm.nih.gov/pubmed/25947045", "http://www.ncbi.nlm.nih.gov/pubmed/8882776", "http://www.ncbi.nlm.nih.gov/pubmed/9040786", "http://www.ncbi.nlm.nih.gov/pubmed/12437640", "http://www.ncbi.nlm.nih.gov/pubmed/19758696", "http://www.ncbi.nlm.nih.gov/pubmed/8362906", "http://www.ncbi.nlm.nih.gov/pubmed/10330122", "http://www.ncbi.nlm.nih.gov/pubmed/26815134", "http://www.ncbi.nlm.nih.gov/pubmed/14749005", "http://www.ncbi.nlm.nih.gov/pubmed/24405535", "http://www.ncbi.nlm.nih.gov/pubmed/20226525", "http://www.ncbi.nlm.nih.gov/pubmed/8207974", "http://www.ncbi.nlm.nih.gov/pubmed/10598142", "http://www.ncbi.nlm.nih.gov/pubmed/8149646", "http://www.ncbi.nlm.nih.gov/pubmed/19806569", "http://www.ncbi.nlm.nih.gov/pubmed/12040758", "http://www.ncbi.nlm.nih.gov/pubmed/17701956", "http://www.ncbi.nlm.nih.gov/pubmed/24604040", "http://www.ncbi.nlm.nih.gov/pubmed/12616613", "http://www.ncbi.nlm.nih.gov/pubmed/18428311", "http://www.ncbi.nlm.nih.gov/pubmed/16468325", "http://www.ncbi.nlm.nih.gov/pubmed/10408793", "http://www.ncbi.nlm.nih.gov/pubmed/27576943", "http://www.ncbi.nlm.nih.gov/pubmed/20677157", "http://www.ncbi.nlm.nih.gov/pubmed/7977469", "http://www.ncbi.nlm.nih.gov/pubmed/23450488", "http://www.ncbi.nlm.nih.gov/pubmed/11783350", "http://www.ncbi.nlm.nih.gov/pubmed/9831340", "http://www.ncbi.nlm.nih.gov/pubmed/24398791", "http://www.ncbi.nlm.nih.gov/pubmed/24370037", "http://www.ncbi.nlm.nih.gov/pubmed/8723064", "http://www.ncbi.nlm.nih.gov/pubmed/17649717", "http://www.ncbi.nlm.nih.gov/pubmed/7649555", "http://www.ncbi.nlm.nih.gov/pubmed/18000985", "http://www.ncbi.nlm.nih.gov/pubmed/14666267", "http://www.ncbi.nlm.nih.gov/pubmed/12116251", "http://www.ncbi.nlm.nih.gov/pubmed/10485139", "http://www.ncbi.nlm.nih.gov/pubmed/26392809", "http://www.ncbi.nlm.nih.gov/pubmed/18591625", "http://www.ncbi.nlm.nih.gov/pubmed/17653548", "http://www.ncbi.nlm.nih.gov/pubmed/7666455", "http://www.ncbi.nlm.nih.gov/pubmed/21223721", "http://www.ncbi.nlm.nih.gov/pubmed/7934162" ], "ideal_answer": [ "To explore the clonal evolution of monosomy 7 in patients with aplastic anemia (AA).Monosomy 7 (-7) in 81 AA patients with normal karyotype at diagnosis and 46 AA treated with immunosuppressive therapy (IST) and more than 6 months of recombinant human granulocyte colony-stimulating factor (rhuG-CSF) were detected by interphase- fluorescence in situ hybridization (FISH) retrospectively.There were 5.4% - 7.6% of -7 cells in 11 (13.6%) of 81 patients at diagnosis, the survival and response rate to IST in -7 positive patients did not differ s Former molecular cytogenetic studies showed that such aberrations as an equivalent of intrinsic radiosensitivity can be detected by fluorescence in-situ hybridization (FISH) techniques using whole chromosome painting (wcp) probes. Five-color FISH was performed using human DNA segments specific for peri-CEN or subTEL, which were labeled with five different fluorescent dyes [7-diethylaminocoumarin (DEAC): blue, fluorescein isothiocyanate (FITC): green, rhodamine 6G (R6G): yellow, TexRed: red, and cyanine5 (Cy5): purple]. Using this technique, followed by cell-by-cell multicolor fluorescence in situ hybridization (FISH) analysis of purified FNRBCs, we were able to detect some of the most common human aneuploidies (including Down syndrome, Klinefelter syndrome, and trisomy 13) in 33 pregnant women referred for amniocentesis.", "The human syndromes which can be detected with FISH are:\n1) Myelodysplastic Syndrome (MDS)\n2) Genetic syndromes caused by somatic chromosomal mosaicism\n3) Prader Willi syndrome (PWS)\n4) Angelman syndrome (AS)\n5) Williams syndrome\n6) Smith Magenis syndrome \n7) Velocardiofacial syndrome\n8) Jacobsen syndrome\n9) Shwachman-Diamond syndrome\n10) Saethre-Chotzen syndrome \n11) DiGeorge syndrome (DGS) \n12) Velo-cardio-facial syndrome (VCFS)\n13) Miller-Dieker syndrome\n14) Deletion 22q11.2 syndrome (D22S)" ], "exact_answer": [ [ "Myelodysplastic Syndrome", "MDS" ], [ "Genetic syndromes caused by somatic chromosomal mosaicism" ], [ "Prader Willi syndrome", "PWS" ], [ "Angelman syndrome", "AS" ], [ "Williams syndrome" ], [ "Smith Magenis syndrome" ], [ "Velocardiofacial syndrome" ], [ "Jacobsen syndrome" ], [ "Shwachman-Diamond syndrome" ], [ "Saethre-Chotzen syndrome" ], [ "DiGeorge syndrome", "DGS" ], [ "Velo-cardio-facial syndrome", "VCFS" ], [ "Miller-Dieker syndrome" ], [ "Deletion 22q11.2 syndrome", "D22S" ], [ "Down syndrome", "Trisomy 21", "DS", "DNS" ], [ "Klinefelter Syndrome", "47", "XXY", "KS" ], [ "Trisomy 13", "Patau Syndrome" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017404", "http://www.disease-ontology.org/api/metadata/DOID:11983", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013050", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011218", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017403" ], "type": "list", "id": "58932cd87d9090f353000001", "snippets": [ { "offsetInBeginSection": 806, "offsetInEndSection": 1077, "text": "We demonstrate that, using a sensitive FISH technique, 12p deletion occurs significantly more frequently in MDS than previously described (7.6% by CD34+ PB-FISH vs. 1.6% by CBA, P<0.001) and is often associated with other aberrations (93% by CD34+ PB-FISH vs. 60% by CBA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26355708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Somatic chromosomal mosaicism arising from post-zygotic errors is known to cause several well-defined genetic syndromes as well as contribute to phenotypic variation in diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24398791", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 931, "text": "The mosaicism was characterized and confirmed by fluorescence in situ hybridization (FISH) and/or chromosome analysis. Different categories of abnormal cell lines were detected: (1) aneuploidy, including sex chromosome abnormalities and isochromosomes (22 cases), (2) ring or marker chromosomes (12 cases), (3) single deletion/duplication copy number variations (CNVs) (11 cases), (4) multiple deletion/duplication CNVs (5 cases), (5) exonic CNVs (4 cases), and (6) unbalanced translocations (3 cases). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24398791", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1147, "text": "Positive cases with MLPA technique were confirmed using either fluorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24604040", "endSection": "abstract" }, { "offsetInBeginSection": 1555, "offsetInEndSection": 1739, "text": "The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24604040", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 547, "text": "The bone marrow specimen from a patient with MDS was comprehensively analyzed by a combination of genomic approaches, including chromosomal karyotyping, fluorescence in situ hybridization (FISH), genome scanning using Affymetrix high density SNP microarray platform, and next-generation sequencing (NGS) analysis using IonTorrent Cancer Gene Panel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24370037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Detection of TET2 abnormalities by fluorescence in situ hybridization in 41 patients with myelodysplastic syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749034", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Fluorescence in situ hybridization of TP53 for the detection of chromosome 17 abnormalities in myelodysplastic syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25754580", "endSection": "title" }, { "offsetInBeginSection": 222, "offsetInEndSection": 356, "text": "Fluorescence in situ hybridization (FISH) can effectively demonstrate TET2 deletions and is often used to validate molecular results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749034", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1285, "text": "These findings demonstrate that 1) FISH is an effective and economical method to reveal cryptic abnormalities of band 4q22-q24 resulting in TET2 deletions;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "FISH and SNP-A karyotyping in myelodysplastic syndromes: improving cytogenetic detection of del(5q), monosomy 7, del(7q), trisomy 8 and del(20q).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19758696", "endSection": "title" }, { "offsetInBeginSection": 603, "offsetInEndSection": 875, "text": " Using a standardized approach, we focused our investigation on detection of -5/del(5q), -7/del(7q), trisomy 8 and del(20q) in patients with MDS (N=52), MDS/myeloproliferative overlap syndromes (N=7) and acute myeloid leukemia (N=15) using MC, FISH and SNP-A karyotyping. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19758696", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1518, "text": "We conclude that MC, FISH and SNP-A are complementary techniques that, when applied and interpreted together, can improve the diagnostic yield for identifying genetic lesions in MDS and contribute to the better description of abnormal karyotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19758696", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 456, "text": "Here, we report the detection of a reciprocal translocation t(7;21)(p22;q22) in the marrow of two adults with MDS and AML, using conventional cytogenetic analysis and fluorescence-in situ-hybridization (FISH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20064152", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 170, "text": "Detection of cytogenetic abnormalities involving chromosomes 5,7 and 8 in myelodysplastic syndromes with fluorescence in situ hybridization and its clinical significance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17649717", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 177, "text": "To identify the abnormal karyotypes by fluorescence in situ hybridization (FISH) and explore prognostic implications in patients with myelodysplastic syndromes (MDS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17649717", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 297, "text": "FISH was used to detect the frequently occurring chromosome abnormalities (-5/5q, +8, -7/7q-) in 37 MDS cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17649717", "endSection": "abstract" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1544, "text": "FISH detected monosomy 7 in 6 samples at the time MDS was diagnosed and in 2 samples at the time AA was diagnosed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17701956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "As chromosomal instability may contribute to leukemogenesis in patients with congenital bone marrow failure (CBMF) disorders, it was the aim of this study to characterize chromosomally aberrant clones that arise during the clinical course of disease by means of R-banding and fluorescence in situ hybridization (FISH) analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653548", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 1232, "text": "In one child with congenital thrombocytopenia, Jacobsen syndrome [del(11)(q24)c] was diagnosed, and thus a CBMF could be excluded. In a girl with Shwachman-Diamond syndrome, two independent clones, one with an isochromosome i(7)(q10), another with a complex aberrant karyotype, were identified. Simultaneously, transition into a myelodysplastic syndrome (MDS) occurred. The brother, who was also afflicted with Shwachman-Diamond syndrome, showed an isochromosome i(7q) as a single aberration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653548", "endSection": "abstract" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1698, "text": "In summary, we suggest that follow-up of patients with CBMF using chromosome and FISH analyses will be helpful for the early detection of transition into MDS or AML and thus should be an integral part of the clinical management of these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653548", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 751, "text": "Here we assess this capability by applying array CGH to the analysis of copy number alterations in 44 patients with a phenotype of the 22q11.2 deletion syndrome. Twenty-five patients had the deletion on chromosome 22 characteristic of this syndrome as determined by fluorescence in situ hybridization (FISH). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17394204", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 1056, "text": "Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2-q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16857771", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 120, "text": "Detection of 20q(-) chromosome abnormality in myelodysplastic syndrome by interphase fluorescence in situ hybridization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12744739", "endSection": "title" }, { "offsetInBeginSection": 698, "offsetInEndSection": 1028, "text": "The results showed that among 52 cases of MDS, 7 (13.5%) cases were positive by FISH, however, of which, 4 cases were positive and the other 3 cases were negative by CC assay. It is concluded that YAC912C3 and interphase FISH providing a powerful technique in the detection of 20q(-) in MDS is an important complement to CC assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12744739", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 418, "text": "A FISH assay was performed to analyze 70 AML/MDS patients who had received conventional cytogenetic analysis (CCA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14669212", "endSection": "abstract" }, { "offsetInBeginSection": 1536, "offsetInEndSection": 1887, "text": "FISH is a powerful tool to identify or refine chromosomal structural aberrations involving 7q, and it provides accurate evaluation of -7/7q- in all the patients. -7 and 7q- clone frequently coexist in the same specimen, and the significantly increasing percentage of 7q- cells implies that -7 clone secondary to 7q- clone is a result from loss of 7q-.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14669212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Saethre-Chotzen syndrome is a common craniosynostosis syndrome characterized by craniofacial and limb anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12116251", "endSection": "abstract" }, { "offsetInBeginSection": 1468, "offsetInEndSection": 1736, "text": "We propose that initial screening for the FGFR3 P250R mutation, followed by sequencing of TWIST and then fluorescence in situ hybridization (FISH) for deletion detection of TWIST, is sufficient to detect mutations in>80% of patients with the Saethre-Chotzen phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12116251", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 983, "text": "We clearly present that the use of SKY combined with conventional G-banding analysis and FISH has assisted in the identification of important chromosomal events that may play a key role in the development of t-MDS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12505257", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 272, "text": "n this study, we used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) as complementary techniques for the analysis of two therapy-related secondary myelodysplastic syndrome (t-MDS) cases with complex karyotypes, previously analyzed by G-banding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12505257", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 141, "text": "Comparison of detection of trisomy 8 with fluorescence in situ hybridization and conventional karyotype analysis in myelodysplastic syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12513811", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 418, "text": "The trisomy 8 clones were simultaneously detected in 48 MDS cases with FISH and conventional cytogenetic analysis (CCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12513811", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 905, "text": "Trisomy 8 was detected in 1 of 15 specimens with normal or abnormal karyotype without trisomy 8 by FISH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12513811", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1381, "text": "In conclusion, our results showed that FISH is a sensitive and accurate technique to detect trisomy 8 in MDS patients. It can provide contribute to diagnosis, assessment of curative effect and predicting progress of disease in MDS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12513811", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 121, "text": "Detection of common chromosome abnormalities in myelodysplastic syndrome with a panel fluorescence in situ hybridization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12673589", "endSection": "title" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1207, "text": "Panel FISH is a useful tool of molecular cytogenetics in the detection of common chromosome abnormalities in MDS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12673589", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 772, "text": "Among 20 cases, 13 cases were found to carry common chromosome abnormalities by panel FISH (trisomy 8, five cases; -5/5q-, one case; 20q-, five cases; 5q- accompanying 20q-, one case; complex abnormalities, one case)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12673589", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 121, "text": "Detection of -5/5q- chromosome abnormality in myelodysplastic syndromes by interphase fluorescence in situ hybridization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11769675", "endSection": "title" }, { "offsetInBeginSection": 498, "offsetInEndSection": 636, "text": "In 48 MDS patients, 13 were positive for interphase FISH, of whom, 7 were positive and 6 were negative for conventional cytogenetics (CC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11769675", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 844, "text": "Interphase FISH is more sensitive than CC for the detection of -5/5q- in MDS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11769675", "endSection": "abstract" }, { "offsetInBeginSection": 571, "offsetInEndSection": 874, "text": "Three cases displayed -7/7q- by conventional cytogenetics(CC) and were confirmed by interphase FISH. Six cases in 43 cases who did not show -7/7q- by CC displayed -7/7q- by interphase FISH.CONCLUSION: Interphase FISH is very useful for the detection of -7 or 7q- in MDS and it is more sensitive than CC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11484160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Diagnosis of microdeletion syndromes by fluorescence in situ hybridization (FISH).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428311", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 103, "text": "Detection of trisomy 8 with interphase fluorescence in situ hybridization in myelodysplastic syndromes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11876976", "endSection": "title" }, { "offsetInBeginSection": 834, "offsetInEndSection": 976, "text": "Interphase FISH was a useful method for the detection of trisomy 8 in MDS, especially in patients with normal karyotype or marker chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11876976", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 315, "text": "Congenital cardiovascular (c-v) malformations are the leading signs of two syndromes of highly variable phenotypes, the DiGeorge syndrome (DGS) and the velo-cardio-facial syndrome (VCFS), both of which in the majority of cases are caused by microdeletion in the chromosome region 22q11.2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951451", "endSection": "abstract" }, { "offsetInBeginSection": 1977, "offsetInEndSection": 2158, "text": "In patients with congenital c-v and associated malformations of dysmorphism microdeletion diagnosis of 22q11.2 by FISH is indicated in addition to conventional cytogenetic testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Discordant detection of monosomy 7 by GTG-banding and FISH in a patient with Shwachman-Diamond syndrome without evidence of myelodysplastic syndrome or acute myelogenous leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10598142", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Fluorescence in situ hybridization of progenitor cells obtained by fluorescence-activated cell sorting for the detection of cells affected by chromosome abnormality trisomy 8 in patients with myelodysplastic syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9763574", "endSection": "title" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1540, "text": "We conclude that the combination of FACS/FISH/BUdR, which determines the number, phenotype and proliferation rate of very rare leukaemic cells in patients with AML or MDS in clinical remission, provides information that is useful in the identification of patients with high and low likelihood of relapse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9359505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "FISH detection of chromosome 15 deletions in Prader-Willi and Angelman syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8882776", "endSection": "title" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1059, "text": "We conclude that FISH analysis is a rapid and reliable method for detection of deletions within 15q11-q13 and whenever a deletion is found, FISH analysis of parental chromosomes should also be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8882776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "We have evaluated fluorescence in situ hybridization (FISH) analysis for the clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN, D15S10, and GABRB3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8882776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Study of clonality in myelodysplastic syndromes: detection of trisomy 8 in bone marrow cell smears by fluorescence in situ hybridization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8795688", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Investigations with fluorescence in situ hybridization (FISH) demonstrate loss of the telomeres on the reciprocal chromosome in three unbalanced translocations involving chromosome 15 in the Prader-Willi and Angelman syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7649555", "endSection": "title" }, { "offsetInBeginSection": 245, "offsetInEndSection": 513, "text": "Fluorescence in situ hybridization (FISH) was used for the detection of chromosome 15(q11-13) deletions (with probes from the PWS/AS region) and to define the involvement of the telomere in the derivative chromosomes (with library probes and telomere-specific probes).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7649555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Fluorescence in situ hybridization improves the detection of monosomy 7 in myelodysplastic syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8207974", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Detection of monosomy 7 by fluorescence in situ hybridization in acute nonlymphocytic leukemia and myelodysplastic syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8260718", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Fluorescence in situ hybridization (FISH) with a chromosome 7 specific alpha satellite DNA probe was used to detect monosomy 7 in interphase and metaphase cells obtained from patients with myelodysplastic syndrome (MDS) and acute nonlymphocytic leukemia (ANLL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8260718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "A 15-year-old male with myelodysplastic syndrome (MDS) characterized by monosomy 7 was cytogenetically evaluated by metaphase karyotyping and fluorescence in situ hybridization (FISH) of interphase cells at six different points during the course of his disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1394103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Fluorescence in situ hybridization (FISH) using two cosmid probes (41A and P13) from the Miller-Dieker syndrome (MDS) critical region in 17p13.3 was performed in a blinded comparison of three MDS patients with submicroscopic deletions and in four normal relatives used as controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1897521", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1172, "text": "These studies demonstrate that in situ hybridization is an efficient method for deletion detection in Miller-Dieker syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1897521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "This study identified cytogenetic abnormalities in a population screened for deletion 22q11.2 syndrome (D22S) by fluorescence in situ hybridization (FISH) and G-banding and correlated these abnormalities to referring specialty and submitted indications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16222476", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 516, "text": "Positive test results for D22S FISH and other abnormalities found by other FISH assays and G-banding were correlated to submitting specialist and indication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16222476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Use of fluorescence in situ hybridization (FISH) in the diagnosis of DiGeorge sequence and related diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8634784", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Deletions of 22q11.2 have been detected in the majority of patients with DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes by either cytogenetic analysis, fluorescence in situ hybridization (FISH), or Southern blot hybridization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10464634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18591625", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 674, "text": "To explore the value of multiplex fluorescence in situ hybridization (M-FISH) technique in the detection of the complex chromosomal aberrations (CCAs) in myelodysplastic syndromes (MDS).M-FISH was used in ten MDS patients with R-banding CCAs to refine the complex chromosomal rearrangements, the constitute of marker chromosomes, and to identify the cryptic translocations.Thirty-seven kinds of structural rearrangements were detected by M-FISH including insertion, deletion, translocation and derivative chromosomes, among which 34 kinds were unbalanced rearrangements, and 3 were balanced rearrangements including t(6;22) (q21; q12), t(9; 19) (q13; p13) and t(3;5) (?; ?).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 598, "text": "To explore the clonal evolution of monosomy 7 in patients with aplastic anemia (AA).Monosomy 7 (-7) in 81 AA patients with normal karyotype at diagnosis and 46 AA treated with immunosuppressive therapy (IST) and more than 6 months of recombinant human granulocyte colony-stimulating factor (rhuG-CSF) were detected by interphase- fluorescence in situ hybridization (FISH) retrospectively.There were 5.4% - 7.6% of -7 cells in 11 (13.6%) of 81 patients at diagnosis, the survival and response rate to IST in -7 positive patients did not differ significantly from that in -7 negative patients (P = 0.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21223721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 487, "text": "To compare the results of fluorescence in situ hybridization (FISH) versus conventional cytogenetics (CC) in the detection of common chromosomal abnormalities and evaluate the significance of FISH in myelodysplastic syndrome (MDS) .A total of 344 patients with de novo MDS from June 2008 to October 2012 were detected by 6 pairs of probes, including CSF1R/D5S23-D5S721 (5q33) , EGR1/ D5S23-D5S721 (5q31) , D7S486 (7q31) /CSP7, D7S522 (7q31) /CSP7, D20S108/CSP8 (20q12/CSP8) and CSPX/CSPY", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24405535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Unbalanced translocation, t(18;21), detected by fluorescence in situ hybridization (FISH) in a child with 18q- syndrome and a ring chromosome 21", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8362906", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 648, "text": "To evaluate the conventional cytogenetic methods in genetic diagnosis and prenatal diagnosis in the family with a proband of Angelman syndrome (AS).High-resolution G-banding karyotyping and fluorescence in situ hybridization (FISH) on metaphase chromosomes were performed.Two AS patients and 1 normal fetus in the family were successfully detected by FISH.Our result demonstrated that patient with type I AS could be detected by combining the techniques of high-resolution G-banding and FISH with clinical observation, which would offer accurate genetic counseling information to the geneticists and provide the prenatal diagnosis for the AS family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19806569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "To investigate the prenatal diagnosis of trisomy 21 syndrome using chromosome 13/21 alpha satellite probe fluorescence in situ hybridization (FISH) on uncultured interphase cells from amniotic fluid.The interphase amniocytes of 10 fetuses who were detected normal and 3 fetus who were detected trisomy by prenatal cytogenetic diagnosis were selected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11783350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 594, "text": "To optimize the prenatal diagnosis platform by using domestically made fluorescence in situ hybridization(FISH) kit and to explore the clinical application of FISH to rapid prenatal diagnosis of a wide range of chromosomal abnormalities.Amniotic fluid samples from 110 pregnant women were studied with the rapid prenatal diagnosis method of FISH and the conventional cell culture method of karyotyping, the results from both methods were compared.Four cases of trisomy 21, 1 case of trisomy 18, 58 cases of 46, XX, and 47 cases of 46, XY were detected by FISH in the 110 amniotic fluid samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20677157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Implementation of Fluorescent in situ hybridization (FISH) as a method for detecting microdeletion syndromes - our first experiences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18356781", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Prenatal detection of cri du chat syndrome on uncultured amniocytes using fluorescence in situ hybridization (FISH).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8149646", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Fluorescence in situ hybridization (FISH) using non-commercial probes in the diagnosis of clinically suspected microdeletion syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056568", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Unbalanced translocation, t(18;21), detected by fluorescence in situ hybridization (FISH) in a child with 18q- syndrome and a ring chromosome 21.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8362906", "endSection": "title" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1032, "text": "Using this technique, followed by cell-by-cell multicolor fluorescence in situ hybridization (FISH) analysis of purified FNRBCs, we were able to detect some of the most common human aneuploidies (including Down syndrome, Klinefelter syndrome, and trisomy 13) in 33 pregnant women referred for amniocentesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11424143", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1293, "text": "FISH with 5p subtelomeric probes and 18p subtelomeric probe further confirmed that the derivative chromosome 5 has derived from a translocation between 5p and 18p, which has given rise to a 46,XY,der(5)t(5;18)(p15.1;p11.31)dn karyotype.A de novo 5p partial deletion in conjunction with a cryptic 18p duplication has been detected in a boy featuring Cri-du-Chat syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450488", "endSection": "abstract" }, { "offsetInBeginSection": 1425, "offsetInEndSection": 1556, "text": "We conclude that FISH is a useful, easily applied technique for the diagnosis of 22q11.2 microdeletion syndromes, particularly DGS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8634784", "endSection": "abstract" }, { "offsetInBeginSection": 1195, "offsetInEndSection": 1765, "text": "In group B (n=79), the 5q deletion had been observed by cytogenetics and was confirmed to be present in all cases by fluorescence in situ hybridization of 5q31.CONCLUSIONS: Fluorescence in situ hybridization of 5q31 detected the 5q deletion in 6% of cases without clear evidence of del(5q) by conventional banding cytogenetics. We suggest that fluorescence in situ hybridization of 5q31 should be performed in cases of a suspected '5q- syndrome' and/or if the cytogenetic study shows no metaphases or an aberrant karyotype with chromosome 5 involved (no 5q- chromosome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18591625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Although conventional cytogenetics is considered the gold standard to detect chromosomal abnormalities in myelodysplastic syndromes (MDS), fluorescence in situ hybridization (FISH) is being increasingly used additionally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20226525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Cytogenetic aberrations in myelodysplastic syndrome detected by comparative genomic hybridization and fluorescence in situ hybridization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408793", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "To detect chromosomal abnormalities in myelodysplastic syndrome (MDS) patients by fluorescence in situ hybridization (FISH) and conventional cytogenetic analysis (CCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25011965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Comparison of high resolution chromosome banding and fluorescence in situ hybridization (FISH) for the laboratory evaluation of Prader-Willi syndrome and Angelman syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7977469", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Deletion of small nuclear ribonucleoprotein polypeptide N (SNRPN) in Prader-Willi syndrome detected by fluorescence in situ hybridization: two sibs with the typical phenotype without a cytogenetic deletion in chromosome 15q.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8723064", "endSection": "title" }, { "offsetInBeginSection": 133, "offsetInEndSection": 254, "text": "We describe two sibs with typical PWS presenting deletion of SNRPN detected by fluorescence in situ hybridization (FISH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8723064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Use of fluorescence in situ hybridization (FISH) in the diagnosis of DiGeorge sequence and related diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8634784", "endSection": "title" } ] }, { "body": "List symptoms of EAST syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27500072", "http://www.ncbi.nlm.nih.gov/pubmed/21300747", "http://www.ncbi.nlm.nih.gov/pubmed/21633011", "http://www.ncbi.nlm.nih.gov/pubmed/23471908", "http://www.ncbi.nlm.nih.gov/pubmed/23924083", "http://www.ncbi.nlm.nih.gov/pubmed/20651251", "http://www.ncbi.nlm.nih.gov/pubmed/21849804", "http://www.ncbi.nlm.nih.gov/pubmed/21221631" ], "ideal_answer": [ "Epilepsy, ataxia, sensorineural deafness, and tubulopathy comprise EAST syndrome that is associated with recessive mutations in the KCNJ10 gene." ], "exact_answer": [ [ "epilepsy" ], [ "ataxia" ], [ "sensorineural deafness" ], [ "tubulopathy" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816" ], "type": "list", "id": "589a246378275d0c4a00002c", "snippets": [ { "offsetInBeginSection": 191, "offsetInEndSection": 362, "text": "This condition is characterized by 4 cardinal features; Epilepsy, Ataxia, Sensorineural deafness, and (a renal salt-wasting) Tubulopathy, hence the acronym EAST syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27500072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Generation and validation of a zebrafish model of EAST (epilepsy, ataxia, sensorineural deafness and tubulopathy) syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23471908", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Recessive mutations in KCNJ10, which encodes an inwardly rectifying potassium channel, were recently identified as the cause of EAST syndrome, a severe and disabling multi-organ disorder consisting of epilepsy, ataxia, sensorineural deafness and tubulopathy that becomes clinically apparent with seizures in infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23471908", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 861, "text": "We next injected splice- and translation-blocking kcnj10 antisense morpholino oligonucleotides and reproduced the cardinal symptoms of EAST syndrome - ataxia, epilepsy and renal tubular defects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23471908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "AIM: Recently, we reported a previously unrecognized symptom constellation comprising epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) associated with recessive mutations in the KCNJ10 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23924083", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1498, "text": "EAST syndrome should be considered in any patient with a renal Gitelman-like phenotype with additional neurological signs and symptoms like ataxia, epilepsy or sensorineural deafness.Copyright \u00a9 2011 S. Karger AG, Basel.200 microg/min).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20520578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Surfactant protein A (SP-A) binds to phosphatidylserine and competes with annexin V binding on late apoptotic cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21203987", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14676140", "endSection": "title" }, { "offsetInBeginSection": 86, "offsetInEndSection": 469, "text": "Because annexin V has a high affinity for exposed phosphatidylserine on apoptotic cells, radiolabeled annexin V may be used for noninvasive detection of apoptosis in atherosclerotic lesions.Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the infradiaphragmatic aorta followed by 12 weeks of cholesterol diet; 5 controls were studied without manipulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14676140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20122665", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Synthesis and evaluation of a 18F-labelled recombinant annexin-V derivative, for identification and quantification of apoptotic cells with PET.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12573319", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Sensitive and visible detection of apoptotic cells on Annexin-V modified substrate using aminophenylboronic acid modified gold nanoparticles (APBA-GNPs) labeling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24021657", "endSection": "title" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1148, "text": "Fluorescence-activated cell sorting (FACS) for expression of the early apoptosis marker Annexin V and for nuclear staining by 7-aminoactinomycin (7-AAD) revealed different extents of apoptosis versus non-apoptotic cell death for the three agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960471", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 876, "text": "At immunofluorescence these cells contained lipid vesicles positive for the apoptotic cell marker Annexin V suggesting the phagocytosis of apoptotic bodies derived from dead fat-laden hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26112094", "endSection": "abstract" }, { "offsetInBeginSection": 1612, "offsetInEndSection": 1708, "text": "In this respect, we identified binding of Annexin V as an convenient marker for apoptotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7812008", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 697, "text": "DR5 expression was elevated and associated with the apoptotic marker annexin V. Apoptosis was reduced in CD4(+) T cells when cultured with anti-DR5 antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16046522", "endSection": "abstract" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1080, "text": "Flow cytometric analysis using the apoptotic marker, Annexin V, shows that this endogenous re-expression is sufficient to drive the SCLC cells to apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116573", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 853, "text": "Apoptotic cell death was evaluated by staining nuclei with propidium iodide and phosphatidylserine (a marker of early apoptotic events) with Annexin V as well as by DNA fragmentation assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16253964", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 638, "text": "Decreased cell growth was not caused by cell death as BEL exposure did not alter nuclear morphology or increase annexin V (apoptotic cell marker) or propidium iodide (necrotic cell marker) staining after 48 h.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18441250", "endSection": "abstract" }, { "offsetInBeginSection": 2979, "offsetInEndSection": 3261, "text": "Four populations of cells can be identified: region R1: vital cells (annexin V negative/PI negative), region R2: apoptotic cells (annexin V positive/PI negative), region R3: dead cells (annexin V positive/ PI positive); and region R4: damaged cells (annexin V negative/PI positive).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21340828", "endSection": "abstract" }, { "offsetInBeginSection": 2109, "offsetInEndSection": 2222, "text": "Furthermore, uptake of (111)In-DTPA-PEG-annexin V by tumors correlated with apoptotic index (r = 0.87, P = 0.02).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14734682", "endSection": "abstract" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1309, "text": "Annexin V(+)/PI(-) cells were characterized as early apoptotic, Annexin V(+)/PI(+) as late apoptotic and Annexin V(-)/PI(+) as dead.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20430734", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 580, "text": "Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27619241", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 923, "text": "[18F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14666384", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 714, "text": "The viability of SiHa cells was evaluated using the MTT assay, apoptosis by acridine orange/ethidium bromide, propidium iodide, TUNEL assay, and Annexin V-Cy3, cell cycle distribution and mitochondrial transmembrane potential using flow cytometry, and apoptotic marker genes using quantitative real-time PCR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22913657", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1325, "text": "Furthermore, hesperetin-induced apoptosis was confirmed by TUNEL and Annexin V-Cy3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22913657", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 274, "text": "The procedure delivers two sperm fractions: annexin V-negative (nonapoptotic) and annexin V-positive (apoptotic).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16306419", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 811, "text": "The percentage of cells stained with annexin V, an early apoptotic marker, increased dramatically after cytoskeletal disruption with cytochalasin D compared with non-cytochalasin-D-treated controls (P<0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16740972", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 498, "text": "Apoptotic marker Annexin V analysis showed that the apoptotic rate of NB4 cells was increased after treatment with quercetin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16737615", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 291, "text": "The cytomorphology of NB4 cells was assessed by Wright-stain, apoptosis rate by apoptotic marker Annexin V, and VEGF secretion level by ELISA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16737615", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 923, "text": " We have coupled annexin V with the bifunctional hydrazinonicotinamide reagent (HYNIC) to prepare technetium-99m HYNIC-annexin V and demonstrated localization of radioactivity in tissues undergoing apoptosis in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10541822", "endSection": "abstract" }, { "offsetInBeginSection": 2914, "offsetInEndSection": 3070, "text": "In conlusion, these studies confirm the value of (99m)Tc-HYNIC-annexin V uptake as a marker for the detection and quantification of apoptotic cells in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10541822", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1265, "text": "The application of Annexin V labeling at electron microscopy will allow a more refined description of the morphological events occurring during apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9359032", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 753, "text": "Apoptotic cells were identified by Annexin V-FITC/PI staining. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25591763", "endSection": "abstract" } ] }, { "body": "Which are the lipid lowering drugs administered in patients with Coronary Artery Disease (CAD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23074505", "http://www.ncbi.nlm.nih.gov/pubmed/23409830", "http://www.ncbi.nlm.nih.gov/pubmed/15174957", "http://www.ncbi.nlm.nih.gov/pubmed/19801853", "http://www.ncbi.nlm.nih.gov/pubmed/19090788", "http://www.ncbi.nlm.nih.gov/pubmed/23538020", "http://www.ncbi.nlm.nih.gov/pubmed/20574136", "http://www.ncbi.nlm.nih.gov/pubmed/10987597", "http://www.ncbi.nlm.nih.gov/pubmed/10637948", "http://www.ncbi.nlm.nih.gov/pubmed/19563393", "http://www.ncbi.nlm.nih.gov/pubmed/25934512", "http://www.ncbi.nlm.nih.gov/pubmed/15809368", "http://www.ncbi.nlm.nih.gov/pubmed/18674471", "http://www.ncbi.nlm.nih.gov/pubmed/11113401", "http://www.ncbi.nlm.nih.gov/pubmed/11597936", "http://www.ncbi.nlm.nih.gov/pubmed/24527682", "http://www.ncbi.nlm.nih.gov/pubmed/27923158", "http://www.ncbi.nlm.nih.gov/pubmed/18973424", "http://www.ncbi.nlm.nih.gov/pubmed/20671371", "http://www.ncbi.nlm.nih.gov/pubmed/16098846", "http://www.ncbi.nlm.nih.gov/pubmed/25999102", "http://www.ncbi.nlm.nih.gov/pubmed/20124992" ], "ideal_answer": [ "The lipid lowering drugs administered in patients with Coronary Artery Disease (CAD) are:\n1) Statins\n2) Fibrates\n3) Resins\n4) Niacin\n5) Cholesterol absorption-inhibiting drugs." ], "exact_answer": [ [ "Statins" ], [ "Fibrates" ], [ "Resins" ], [ "Niacin" ], [ "Cholesterol absorption-inhibiting drugs" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3393", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003327" ], "type": "list", "id": "589c42b178275d0c4a00003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Impact of adding ezetimibe to statin to achieve low-density lipoprotein cholesterol goal (from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE] trial).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538020", "endSection": "title" }, { "offsetInBeginSection": 544, "offsetInEndSection": 658, "text": "After maximizing statin dose, ezetimibe was added to reach the LDL cholesterol goal in 34% of patients (n\u00a0= 734). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538020", "endSection": "abstract" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1607, "text": "Using Cox regression analysis, the most significant factors associated with achieving LDL cholesterol goals were lower baseline LDL cholesterol, average statin dose, and ezetimibe use. In conclusion, after maximizing statin dose, the addition of ezetimibe results in a substantial increase in the percentage of patients who reach LDL cholesterol goal, a key component of optimal medical therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Comparative study of bezafibrate and pravastatin in patients with coronary artery disease and high levels of remnant lipoprotein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20574136", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 297, "text": "Remnant lipoproteinemia is a strong risk factor for cardiovascular (CV) diseases. This study examined which of 2 common lipid-lowering drugs (fibrates and statins) is more effective in patients with remnant lipoproteinemia and if lowering remnant lipoprotein levels can reduce CV risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20574136", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 896, "text": "RLP-C levels at 1 year of treatment were reduced more by bezafibrate than pravastatin (37% and 25% from baseline, respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20574136", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1438, "text": "Bezafibrate therapy decreased RLP-C levels to a greater extent than pravastatin and a decrease in RLP-C level may be associated with a reduction in CV events in patients with high RLP-C levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20574136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Statins are powerful lipid-lowering drugs, widely used in patients with hyperlipidemia and coronary artery disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18973424", "endSection": "abstract" }, { "offsetInBeginSection": 3479, "offsetInEndSection": 3636, "text": "Patients are frequently treated with lipid-lowering drugs such as resins, fibrates, niacin, statins and cholesterol absorption-inhibiting drugs (ezetimibe). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23074505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 590, "text": "This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy.There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD.This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without statins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25999102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "To investigate the impact of lipid lowering therapy by different means on skin microvascular function in patients with dysglycaemia and coronary artery disease (CAD).Thirty-six patients were randomized to simvastatin 80 mg daily (S80, n = 19) or ezetimibe 10 mg and simvastatin 10 mg daily (E10/S10, n = 17) for 6 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19563393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Large clinical trials have elucidated that lipid-lowering therapy using statins reduces cardiovascular events in patients with coronary artery disease (CAD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20671371", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 342, "text": "The aim of the present study was to investigate whether LLT (lipid-lowering therapy) with statins could attenuate EPC telomere erosion in patients with CAD (coronary artery disease)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19090788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Beneficial effects of pravastatin (+/-colestyramine/niacin) initiated immediately after a coronary event (the randomized Lipid-Coronary Artery Disease [L-CAD] Study).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11113401", "endSection": "title" } ] }, { "body": "What are PD-1 inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27534574", "http://www.ncbi.nlm.nih.gov/pubmed/25682878", "http://www.ncbi.nlm.nih.gov/pubmed/22740686", "http://www.ncbi.nlm.nih.gov/pubmed/26775720", "http://www.ncbi.nlm.nih.gov/pubmed/27936870", "http://www.ncbi.nlm.nih.gov/pubmed/26588948", "http://www.ncbi.nlm.nih.gov/pubmed/26177645", "http://www.ncbi.nlm.nih.gov/pubmed/26581237", "http://www.ncbi.nlm.nih.gov/pubmed/18203952", "http://www.ncbi.nlm.nih.gov/pubmed/26346135", "http://www.ncbi.nlm.nih.gov/pubmed/26567614", "http://www.ncbi.nlm.nih.gov/pubmed/27310809", "http://www.ncbi.nlm.nih.gov/pubmed/24402925", "http://www.ncbi.nlm.nih.gov/pubmed/27059553", "http://www.ncbi.nlm.nih.gov/pubmed/27063329", "http://www.ncbi.nlm.nih.gov/pubmed/27729774", "http://www.ncbi.nlm.nih.gov/pubmed/23032366", "http://www.ncbi.nlm.nih.gov/pubmed/26598057", "http://www.ncbi.nlm.nih.gov/pubmed/27622603", "http://www.ncbi.nlm.nih.gov/pubmed/25823918", "http://www.ncbi.nlm.nih.gov/pubmed/26477470", "http://www.ncbi.nlm.nih.gov/pubmed/27573048", "http://www.ncbi.nlm.nih.gov/pubmed/27291635", "http://www.ncbi.nlm.nih.gov/pubmed/26850630", "http://www.ncbi.nlm.nih.gov/pubmed/26041735", "http://www.ncbi.nlm.nih.gov/pubmed/27553906" ], "ideal_answer": [ "The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) are used to treat cancer. " ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061026", "http://www.uniprot.org/uniprot/PDCD1_MOUSE" ], "type": "summary", "id": "58a3196360087bc10a00000b", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 354, "text": " The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) have shown activity in several tumor types with preliminary data suggesting a relationship between PD-L1 expression and response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26775720", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 329, "text": "Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26588948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Checkpoint inhibitors with monoclonal antibodies targeting the CTLA-4 or PD-1 axis have revolutionized treatment in some solid tumors, especially melanoma and lung", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26581237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "In recent years, the introduction and Federal Drug Administration approval of immune checkpoint inhibitor antibodies has dramatically improved the clinical outcomes for patients with advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26850630", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 618, "text": "Nivolumab and pembrolizumab target programmed cell death protein 1 (PD-1) receptors and have proven to be superior to ipilimumab alone. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26850630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25823918", "endSection": "title" }, { "offsetInBeginSection": 570, "offsetInEndSection": 738, "text": "PD-1 inhibitors are also poised to become standard of care treatment for other cancers, including non-small cell lung cancer, renal cell carcinoma and Hodgkins lymphoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25682878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "PD-1 inhibitors raise survival in NSCLC", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24402925", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "PD-1 inhibitors raise survival in NSCLC.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24402925", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18203952", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "The development of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors has changed the landscape of non-small-cell lung cancer (NSCLC) therapy, with 2 approvals from the US Food and Drug Administration of PD-1 inhibitors for second-line therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27310809", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 506, "text": "In this article, we will review the unique biologic features that predispose cHL to PD-1 inhibition, current data regarding the safety and efficacy of PD-1 inhibitors in the treatment of cHL, biomarkers of immune response, ongoing clinical trials with PD-1 inhibitors, as well as areas of uncertainty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27622603", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 368, "text": "To determine how PD-1 signaling inhibits T cell proliferation, we used human CD4(+) T cells to examine the effects of PD-1 signaling on the molecular control of the cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22740686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "PD-1 inhibits T cell proliferation by upregulating p27 and p15 and suppressing Cdc25A.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23032366", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "The field of immuno-oncology has witnessed unprecedented success in recent years, with several programmed cell death 1 and PD-L1 inhibitors obtaining US FDA registration and breakthrough drug therapy designation in multiple tumor types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27936870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The use of antibodies against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, has dramatically improved the prognosis of patients with advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27291635", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 420, "text": " Since 2010, treatment options for metastatic melanoma have been developed including chemotherapies, checkpoint inhibition immunotherapies, e.g., anti\u2011cytotoxic T\u2011lymphocyte antigen\u20114\u00a0(CTLA\u20114) and anti\u2011programmed death\u20111\u00a0(PD\u20111), and molecular-targeted therapies, e.g., BRAF and MEK inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573048", "endSection": "abstract" }, { "offsetInBeginSection": 1455, "offsetInEndSection": 1686, "text": "his strategy may be particularly advantageous for vaccines targeting prostate cancer, a disease for which antitumor vaccines have demonstrated clinical benefit and yet PD-1 pathway inhibitors alone have shown little efficacy to dat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26041735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Manipulation of co-stimulatory or co-inhibitory checkpoint proteins allows for the reversal of tumor-induced T-cell anergy observed in cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26567614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Colorectal cancers (CRCs) have been identified as potential targets for immunotherapy with programmed cell death (PD)-1 inhibitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27553906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Blockading the interaction of programmed death-1 (PD-1) protein with its ligands (PD-Ls, such as PD-L1) was proved to be a pathway for suppressing the development of tumors and other degradations of biological species. Thus, finding PD-1 inhibitors situated at the convergence point of drug discovery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27063329", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 124, "text": "Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entitie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729774", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 135, "text": " Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27059553", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 424, "text": "The effectiveness of a CTLA-targeted antibody in treating melanoma was an impetus for the use of programmed cell death-1 (PD-1) inhibitors in cancer treatmen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598057", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 189, "text": " Monoclonal antibodies that target the programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) pathway have shown antitumour activity in metastatic renal cell carcinoma (mRCC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346135", "endSection": "abstract" } ] }, { "body": "Is the protein lefty an inhibitor of nodal?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26506307", "http://www.ncbi.nlm.nih.gov/pubmed/25669884", "http://www.ncbi.nlm.nih.gov/pubmed/25672326", "http://www.ncbi.nlm.nih.gov/pubmed/25684355", "http://www.ncbi.nlm.nih.gov/pubmed/26377939" ], "ideal_answer": [ "Yes, lefty is an inhibitor of nodal." ], "exact_answer": "yes", "type": "yesno", "id": "58a93877ee23e0236b000001", "snippets": [ { "offsetInBeginSection": 99, "offsetInEndSection": 178, "text": "The expression of lefty, an inhibitor of nodal is often reduced in tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25672326", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 416, "text": " Nodal, and an inhibitor, Lefty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25684355", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1097, "text": "as well as the expression of Lefty, an inhibitor of nodal signaling,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26377939", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 648, "text": "he Nodal inhibitor lefty", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25669884", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 367, "text": "The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26506307", "endSection": "abstract" } ] }, { "body": "List drugs withdrawn from the market for cardiovascular adverse events.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21265828", "http://www.ncbi.nlm.nih.gov/pubmed/21412876", "http://www.ncbi.nlm.nih.gov/pubmed/26934640", "http://www.ncbi.nlm.nih.gov/pubmed/19034038", "http://www.ncbi.nlm.nih.gov/pubmed/21249650", "http://www.ncbi.nlm.nih.gov/pubmed/25084209", "http://www.ncbi.nlm.nih.gov/pubmed/16255660", "http://www.ncbi.nlm.nih.gov/pubmed/19933959", "http://www.ncbi.nlm.nih.gov/pubmed/25114779", "http://www.ncbi.nlm.nih.gov/pubmed/23424288", "http://www.ncbi.nlm.nih.gov/pubmed/16119973", "http://www.ncbi.nlm.nih.gov/pubmed/25806762", "http://www.ncbi.nlm.nih.gov/pubmed/25340915", "http://www.ncbi.nlm.nih.gov/pubmed/21751825", "http://www.ncbi.nlm.nih.gov/pubmed/18782007" ], "ideal_answer": [ "Over the years, a number of different drugs have been withdrawn for Cardiotoxicity. Drugs like Clobutinol, that induce cardiac arrhythmias by a blockade of the potassium channel coded by the hERG channel, sibutramine for weight loss and Cox2 inhibitors, Rofecoxib and Valdecoxib have been withdrawn from the market." ], "exact_answer": [ [ "Rofecoxib" ], [ "Valdecoxib" ], [ "Sibutramine" ], [ "Clobutinol" ], [ "Sertindole" ], [ "aprotinin" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064420", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069451" ], "type": "list", "id": "58a326da60087bc10a00000e", "snippets": [ { "offsetInBeginSection": 351, "offsetInEndSection": 538, "text": " rofecoxib was voluntarily removed from the market for increased cardiovascular risk and in April 2005, valdecoxib was also withdrawn, at least in part, due to excess cardiovascular risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16255660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "A common over-the-counter (OTC) non-opioid antitussive drug, clobutinol, was recently withdrawn from the market due to its potential to induce cardiac arrhythmias by a blockade of the potassium channel coded by the human ether-\u00e0-go-go-related gene (hERG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19034038", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1186, "text": "n. However, despite this, at the time of writing orlistat (Europe; USA) remains the only drug currently marketed for the treatment of obesity, with sibutramine having recently been withdrawn from sale globally due to the increased incidence of serious, non-fatal cardiovascular events", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21265828", "endSection": "abstract" }, { "offsetInBeginSection": 1775, "offsetInEndSection": 1900, "text": "Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23424288", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 832, "text": "Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25114779", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 1238, "text": "The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death.To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death.We searched: the Cochrane Injuries Groups Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21412876", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 1238, "text": "The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death.To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death.We searched: the Cochrane Injuries Groups Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249650", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 801, "text": "Rofecoxib and valdecoxib have been withdrawn from the market worldwide due to safety concerns (most importantly for cardiovascular adverse events) and lumiracoxib has been withdrawn in many countries due to liver toxicity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340915", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 777, "text": "In the SCOUT (Sibutramine Cardiovascular OUTcomes) study, sibutramine increased serious cardiovascular events, such as stroke or myocardial infarction, compared with placebo, and was consequently withdrawn from the market", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21751825", "endSection": "abstract" }, { "offsetInBeginSection": 1777, "offsetInEndSection": 1903, "text": "Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23424288", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 802, "text": "Rofecoxib and valdecoxib have been withdrawn from the market worldwide due to safety concerns (most importantly for cardiovascular adverse events) and lumiracoxib has been withdrawn in many countries due to liver toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340915", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 357, "text": "Sertindole , first withdrawn from the market for cardiovascular safety concerns, is currently available in many countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25084209", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 1193, "text": "In the SCOUT (Sibutramine Cardiovascular OUTcomes) study, sibutramine increased serious cardiovascular events, such as stroke or myocardial infarction, compared with placebo, and was consequently withdrawn from the market. The lesson learnt from this is the importance of patient selection, limiting the duration of treatment and stopping treatment in non-responders. Currently, phentermine and amfepramone (diethylpropion) are approved for short-term treatment of obesity (up to 3 months) and orlistat is approved for longer-term treatment; however, the gastrointestinal adverse effects of orlistat may be intolerable for some patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21751825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "BACKGROUND: Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23424288", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 778, "text": "In the SCOUT (Sibutramine Cardiovascular OUTcomes) study, sibutramine increased serious cardiovascular events, such as stroke or myocardial infarction, compared with placebo, and was consequently withdrawn from the market.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21751825", "endSection": "abstract" }, { "offsetInBeginSection": 1730, "offsetInEndSection": 1855, "text": "Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23424288", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 303, "text": " Rofecoxib, a selective cyclo-oxygenase (COX)-2 inhibitor, was a widely marketed drug that was used for relief of pain and inflammation in arthritic conditions. It was withdrawn from the market worldwide in September 2004 because of an increased risk of cardiovascular events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16119973", "endSection": "abstract" } ] }, { "body": "Is Migalastat used for treatment of Fabry Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27834756", "http://www.ncbi.nlm.nih.gov/pubmed/27351440", "http://www.ncbi.nlm.nih.gov/pubmed/27657681", "http://www.ncbi.nlm.nih.gov/pubmed/23176611", "http://www.ncbi.nlm.nih.gov/pubmed/19387866", "http://www.ncbi.nlm.nih.gov/pubmed/24189976", "http://www.ncbi.nlm.nih.gov/pubmed/23474038", "http://www.ncbi.nlm.nih.gov/pubmed/21211680", "http://www.ncbi.nlm.nih.gov/pubmed/21598360", "http://www.ncbi.nlm.nih.gov/pubmed/27509102", "http://www.ncbi.nlm.nih.gov/pubmed/23472096", "http://www.ncbi.nlm.nih.gov/pubmed/27121667", "http://www.ncbi.nlm.nih.gov/pubmed/26252393", "http://www.ncbi.nlm.nih.gov/pubmed/21517827" ], "ideal_answer": [ "Yes, Migalastat is approved for treatment of Fabry disease. Migalastat is an oral pharmacological chaperone developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of \u03b1-Gal to facilitate normal lysosomal trafficking." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14499", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000795" ], "type": "yesno", "id": "5884793ce56acf5176000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27834756", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in \u03b1-galactosidase (\u03b1-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of \u03b1-Gal to facilitate normal lysosomal trafficking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27834756", "endSection": "abstract" }, { "offsetInBeginSection": 1672, "offsetInEndSection": 1844, "text": "CONCLUSIONS: Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27834756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Migalastat (Galafold\u2122)-a small molecule drug developed by Amicus Therapeutics that restores the activity of specific mutant forms of \u03b1-galactosidase-has been approved for the treatment of Fabry disease in the EU in patients with amenable mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27351440", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 652, "text": "This article summarizes the milestones in the development of migalastat leading to this first approval in the EU for the long-term treatment of adults and adolescents aged \u226516 years with a confirmed diagnosis of Fabry disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27351440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27509102", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal \u03b1-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of \u03b1-galactosidase, increasing enzyme trafficking to lysosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27509102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active \u03b1-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252393", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "UNLABELLED: Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of \u03b1-galactosidase A (\u03b1-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472096", "endSection": "title" }, { "offsetInBeginSection": 1567, "offsetInEndSection": 1647, "text": "migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474038", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of \u03b1-galactosidase A (\u03b1-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27121667", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 511, "text": "Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27121667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of \u03b1-galactosidase A (\u03b1-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252393", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1810, "text": "Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.Copyright \u00c2\u00a9 2010 Elsevier Masson SAS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211680", "endSection": "abstract" }, { "offsetInBeginSection": 1305, "offsetInEndSection": 1452, "text": "Migalastat HCl was well tolerated.Migalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23176611", "endSection": "abstract" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1512, "text": "Additionally, these three patients all demonstrated decreases in GL-3 inclusions in kidney peri-tubular capillaries.Migalastat HCl is a candidate oral pharmacological chaperone that provides a potential novel genotype-specific treatment for FD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474038", "endSection": "abstract" }, { "offsetInBeginSection": 1567, "offsetInEndSection": 1750, "text": "migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211680", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1750, "text": "Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27509102", "endSection": "title" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1447, "text": "The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat.Genet Med advance online publication 22 September 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.122..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27657681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474038", "endSection": "title" }, { "offsetInBeginSection": 1646, "offsetInEndSection": 1805, "text": "Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27834756", "endSection": "abstract" } ] }, { "body": "Where are Paneth cells located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21122555", "http://www.ncbi.nlm.nih.gov/pubmed/19397593", "http://www.ncbi.nlm.nih.gov/pubmed/23006982", "http://www.ncbi.nlm.nih.gov/pubmed/24439803", "http://www.ncbi.nlm.nih.gov/pubmed/23232853", "http://www.ncbi.nlm.nih.gov/pubmed/19788585" ], "ideal_answer": [ "Paneth cells are located in the intestinal crypt base columnar cells (CBCCs)." ], "exact_answer": [ "in the intestinal crypt base columnar cells" ], "type": "factoid", "id": "58a9bbe81978bbde22000007", "snippets": [ { "offsetInBeginSection": 615, "offsetInEndSection": 710, "text": "The intestinal stem cell niche comprises both epithelial cells, in particular the Paneth cell, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Paneth cells have been reported in colorectal adenomas and adenocarcinomas;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23232853", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 284, "text": " injury to Paneth cells (PCs) in the intestinal crypts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23006982", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 331, "text": "resence of Paneth cells at the bottom of the crypts of Lieberk\u00fchn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21122555", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 977, "text": "Paneth cells at the crypt base ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19397593", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 776, "text": " Paneth cells (crypt base columnar cells (CBCCs))", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19788585", "endSection": "abstract" } ] }, { "body": "Which are the types of viral meningitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16909784", "http://www.ncbi.nlm.nih.gov/pubmed/22246843", "http://www.ncbi.nlm.nih.gov/pubmed/25042344", "http://www.ncbi.nlm.nih.gov/pubmed/26568804", "http://www.ncbi.nlm.nih.gov/pubmed/22798048", "http://www.ncbi.nlm.nih.gov/pubmed/8972676", "http://www.ncbi.nlm.nih.gov/pubmed/14226105", "http://www.ncbi.nlm.nih.gov/pubmed/21501303", "http://www.ncbi.nlm.nih.gov/pubmed/18680414", "http://www.ncbi.nlm.nih.gov/pubmed/18354820", "http://www.ncbi.nlm.nih.gov/pubmed/6612271", "http://www.ncbi.nlm.nih.gov/pubmed/9810831", "http://www.ncbi.nlm.nih.gov/pubmed/18669052", "http://www.ncbi.nlm.nih.gov/pubmed/21412795", "http://www.ncbi.nlm.nih.gov/pubmed/16849723", "http://www.ncbi.nlm.nih.gov/pubmed/1418647", "http://www.ncbi.nlm.nih.gov/pubmed/14503358", "http://www.ncbi.nlm.nih.gov/pubmed/9265274", "http://www.ncbi.nlm.nih.gov/pubmed/25975649", "http://www.ncbi.nlm.nih.gov/pubmed/25983131", "http://www.ncbi.nlm.nih.gov/pubmed/15927848", "http://www.ncbi.nlm.nih.gov/pubmed/25562123", "http://www.ncbi.nlm.nih.gov/pubmed/24313836", "http://www.ncbi.nlm.nih.gov/pubmed/26334674", "http://www.ncbi.nlm.nih.gov/pubmed/18565120" ], "ideal_answer": [ "Aseptic meningitis is the most common type of meningitis and is characterized by meningeal inflammation that is not linked to identifiable bacterial pathogens in cerebrospinal fluid (CSF). It can be originated from infection from:\n1) Varicella-zoster virus (VZV)\n2) Herpes simplex types I and II (HSV-1, HSV-2)\n3) Epstein-Barr virus (EBV) \n4) Cytomegalovirus (CMV) \n5) Enteroviruses (EV) \n6) Parechoviruses (HPeV) \n7) Human rhinoviruses (HRVs) \n8) Echovirus types 6, 9, 11\n9) West Nile Virus (WNV)" ], "exact_answer": [ [ "Varicella-zoster virus", "VZV" ], [ "Herpes simplex types I and II", "HSV-1", "HSV-2" ], [ "Epstein-Barr virus", "EBV" ], [ "Cytomegalovirus", "CMV" ], [ "Enteroviruses", "EV" ], [ "Parechoviruses", "HPeV" ], [ "Human rhinoviruses", "HRVs" ], [ "Echovirus types 6, 9, 11" ], [ "West Nile Virus", "WNV" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008581", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008582", "http://www.disease-ontology.org/api/metadata/DOID:10310", "http://www.disease-ontology.org/api/metadata/DOID:12157", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008587" ], "type": "list", "id": "589aec4778275d0c4a000037", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 200, "text": "Aseptic meningitis is the most common type of meningitis and is characterized by meningeal inflammation that is not linked to identifiable bacterial pathogens in cerebrospinal fluid (CSF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26568804", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1405, "text": "The results indicate a considerable rate of herpesvirus infection in patients with aseptic meningitis, and that VZV is the most common herpesvirus to cause infection followed by HSV-1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26568804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Detection of herpes viruses in the cerebrospinal fluid of adults with suspected viral meningitis in Malawi.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22798048", "endSection": "title" }, { "offsetInBeginSection": 692, "offsetInEndSection": 994, "text": "Of these, 59 (32 %) had proven meningitis (bacterial, tuberculous or cryptococcal), 39 (21 %) had normal CSF and 14 (8 %) had aseptic meningitis. For the latter group, a herpes virus was detected in 9 (64 %): 7 (50 %) had EBV and 2 (14 %) had CMV, all were human immunodeficiency virus (HIV)-positive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22798048", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1513, "text": "Results confirm that EV-specific RT-PCR can detect HRVs, and at a practical level, identify potential problems of interpretation if fecal samples are used for surrogate screening in cases of suspected viral meningitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Human rhinoviruses (HRVs) can be divided into three species; HRV-A to HRV-C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246843", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 157, "text": "Enteroviruses (EV) and parechoviruses (HPeV) are the most common causes of aseptic meningitis, encephalitis and sepsis-like syndrome in neonates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18354820", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 67, "text": "Serous meningitis associated with primary genital herpes infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9265274", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 497, "text": "Aseptic meningitis is not an uncommon complication to primary genital herpes infection caused by herpes simplex virus type 2 (HSV-2). Compared with other types of viral meningitis, HSV-2-meningitis is associated with a significant rate of neurological complications in the acute stage. In addition, some patients will suffer from recurrent aseptic meningitis (Mollaret's meningitis) later. We describe six patients, five women and one man, age 26-35 years, with aseptic meningitis caused by HSV-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9265274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Viral meningitis due to echovirus types 6 and 9: epidemiological data from Western Australia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8972676", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "During the autumn of 1992, Western Australia experienced a large viral meningitis outbreak of dual aetiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8972676", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 416, "text": "Echovirus 9 caused 41% of cases and occurred mainly in the metropolitan areas of Western Australia whereas echovirus 6, which caused 37% of cases, was more widespread. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8972676", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 154, "text": "Sensitive virologic evaluation in suspected meningitis: study of a radioimmunotest for the detection of IgM antibodies against ECHO 9 and ECHO 11 viruses", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6612271", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The majority of viral meningitis cases is known to be due to ECHO virus infections on one hand, and mumps on the other. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6612271", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 250, "text": "The West Nile Virus (WNV) is a Flavivirus which is transmitted to man by means of different species of mosquitoes and causes outbreaks and sporadic cases of illness in different regions of the Old World, including the Mediterranean Basin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9810831", "endSection": "abstract" }, { "offsetInBeginSection": 1888, "offsetInEndSection": 2254, "text": "Bearing in mind the high percentage of neurological complications found to exist in the most recent outbreaks of WNV infections recorded in the Mediterranean Basin (Bucharest, Algeria), it can be thought that the WNV plays some role in the factors contributing to viral meningitis and encephalitis which occur within the population of the areas at risk within Spain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9810831", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 436, "text": "This study aimed to evaluate the frequency of aseptic meningitis caused by herpesviruses, namely herpes simplex types I and II (HSV-1, HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella-zoster virus (VZV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26568804", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 578, "text": "We compared data obtained from patients with mumps meningitis and patients with aseptic meningitis caused by other viruses in order to identify mumps meningitis-specific cytokine/chemokine alterations in cerebrospinal fluid (CSF).METHODS: \u2002 We elucidated the cytokine/chemokine network based on the cytokine/chemokine profiles in CSF from children with mumps meningitis and meningitis due to other viral infections using multiplex cytokine measurement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "SPORADIC OCCURRENCE OF ECHO VIRUS TYPES 27 AND 31 ASSOCIATED WITH ASEPTIC MENINGITIS IN ONTARIO.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14226105", "endSection": "title" }, { "offsetInBeginSection": 579, "offsetInEndSection": 1536, "text": "Seventeen cytokines/chemokines, namely interleukin (IL)-1\u00e2, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-\u00e3, tumor necrosis factor (TNF)-\u00e1, granulocyte colony-stimulating factor (G-CSF), granulocyte monocyte colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1\u00e2 (MIP-1\u00e2), were measured simultaneously in CSF supernatants from eight children with mumps meningitis, 11 children with other types of viral meningitis and eight children with fever without neurological complications such as convulsion.RESULTS: \u2002 We found that IL-8, IL-10, IL-12, IL-13 and IFN-\u00e3 showed a statistically significant increase in CSF from mumps meningitis when compared to other types of viral meningitis and fever without neurological complications.CONCLUSION: \u2002 Mumps meningitis may induce a distinct immunological response when compared with other types of viral meningitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501303", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1378, "text": "We found that IL-8, IL-10, IL-12, IL-13 and IFN-\u03b3 showed a statistically significant increase in CSF from mumps meningitis when compared to other types of viral meningitis and fever without neurological complications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501303", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1593, "text": "Mumps meningitis may induce a distinct immunological response when compared with other types of viral meningitis.\u00a9 2011 The Authors.Pediatrics International \u00a9 2011 Japan Pediatric Society.\u00a9 2011 The Authors.Pediatrics International \u00a9 2011 Japan Pediatric Society. or = 37.5 degrees C) and administration of the first dose of oseltamivir (0-12 h, 13-24 h, 25-36 h, and 37-48 h)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16838232", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 856, "text": "To clarify the usefulness of oseltamivir in the elderly we administered oseltamivir to all residents when an influenza A outbreak occurred in a nursing home.Sixty-eight residents in the nursing home were investigated in which the influenza A outbreak occurred; 32 residents had fever and 28 residents were positive for influenza A with direct enzyme immunoassay.Oseltamivir was administered at 75 mg twice daily for 5 days to all residents.Oseltamivir almost inhibited symptom onset in the influenza A-positive afebrile group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12058885", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 261, "text": "Oseltamivir was administered to patients with influenza like illness and confirmed influenza, while their close contacts were given oseltamivir prophylactically", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16494733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Insights from investigating the interaction of oseltamivir (Tamiflu) with neuraminidase of the 2009 H1N1 swine flu virus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19523442", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Evaluation of treatment with Oseltamivir during the 2009 H1N1 (swine flu) pandemic: the problem of incomplete clinical information.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22754968", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10708809", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15750458", "endSection": "title" }, { "offsetInBeginSection": 107, "offsetInEndSection": 336, "text": "Oseltamivir (Tamiflu) is a potent and selective antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase (NA), a flu protein responsible for the release and spread of the progeny virions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23794010", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 432, "text": "Oseltamivir is an antiviral drug which works by blocking the function of the viral neuraminidase protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20843284", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 432, "text": "Neuraminidase (NA) inhibitors (Oseltamivir and Zanamivir) are presently used as an anti-flu drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100798", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 613, "text": "US FDA approved Oseltamivir for prophylaxis of uncomplicated influenza A and B. Currently, Oseltamivir is the only first line defense drug available for the treatment of Swine Flu.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20843284", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 872, "text": "Oseltamivir and Zanamivir have good number of interactions with H1N1 2009 virus and the scoring function also support to this result.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100798", "endSection": "abstract" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1480, "text": "The number of interaction and scoring function shows that Oseltamivir and Zanamivir will be able to effectively control the present pandemic H1N1 virus 2009.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Oseltamivir (Tamiflu), a neuraminidase inhibitor, is effective for treating both seasonal flu and H5N1 influenza A virus infection. Oseltamivir is generally well tolerated, and its most common adverse effects are nausea and vomiting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18457919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20885781", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 592, "text": "Approximately 1.4% of tested isolates are oseltamivir resistant. We report a patient with an underlying hematological malignancy who was hospitalized with influenza A (H1N1) swine-origin and whose strain developed oseltamivir resistance during therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20218988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "Oseltamivir (Tamiflu), a neuraminidase inhibitor, is widely used for treatment of influenza. Because abnormal behaviors have been observed in some Japanese teenagers following oseltamivir use, its safety has been questioned. Oseltamivir is known to alter neuronal function and behavior in animals, particularly when administered in combination with ethanol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19273546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "Oseltamivir (Tamiflu), a neuraminidase inhibitor, is effective for treating both seasonal flu and H5N1 influenza A virus infection. Oseltamivir is generally well tolerated, and its most common adverse effects are nausea and vomiting. However, neuropsychiatric behaviors including jumping and falling from balconies by young patients being treated by oseltamivir have been reported from Japan; this has led to warnings against its prescribing by many authorities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18457919", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 322, "text": "However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20885781", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1186, "text": "We observed also 10 infections A/H1N1 influenza during pregnancy, with good oseltamivir tolerance and without recent perinathal complications.CONCLUSIONS: Among 109 individuals with swine flu influenza, 67% have not complicated clinical manifestation and they recovered during 3-4 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20499654", "endSection": "abstract" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1481, "text": "The number of interaction and scoring function shows that Oseltamivir and Zanamivir will be able to effectively control the present pandemic H1N1 virus 2009..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23100798", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1516, "text": "Most reported that oseltamivir was an effective treatment for the flu.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27490658", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 658, "text": "It is needed to perform surveillance on oseltamivir resistance in swine flu.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22666678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The neuraminidase (NA) of influenza virus is the target of anti-flu drugs oseltamivir and zanamivir.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19523442", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 468, "text": "According to one trial, oseltamivir was moderately effective as a prophylactic for close contacts of 'flu cases (6.6% in absolute values).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12825569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Oseltamivir: a first line defense against swine flu.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20843284", "endSection": "title" }, { "offsetInBeginSection": 2312, "offsetInEndSection": 2430, "text": "Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10536125", "endSection": "abstract" } ] }, { "body": "What is the composition of the gamma-secretase complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15591316", "http://www.ncbi.nlm.nih.gov/pubmed/24723404", "http://www.ncbi.nlm.nih.gov/pubmed/24338474", "http://www.ncbi.nlm.nih.gov/pubmed/20299451", "http://www.ncbi.nlm.nih.gov/pubmed/12644463", "http://www.ncbi.nlm.nih.gov/pubmed/27059953", "http://www.ncbi.nlm.nih.gov/pubmed/15766275", "http://www.ncbi.nlm.nih.gov/pubmed/20534834", "http://www.ncbi.nlm.nih.gov/pubmed/15322084", "http://www.ncbi.nlm.nih.gov/pubmed/12821663", "http://www.ncbi.nlm.nih.gov/pubmed/11867728", "http://www.ncbi.nlm.nih.gov/pubmed/12834808", "http://www.ncbi.nlm.nih.gov/pubmed/12684521", "http://www.ncbi.nlm.nih.gov/pubmed/18650432", "http://www.ncbi.nlm.nih.gov/pubmed/17276981", "http://www.ncbi.nlm.nih.gov/pubmed/17560791", "http://www.ncbi.nlm.nih.gov/pubmed/16135086", "http://www.ncbi.nlm.nih.gov/pubmed/16249316", "http://www.ncbi.nlm.nih.gov/pubmed/20130175", "http://www.ncbi.nlm.nih.gov/pubmed/12805296", "http://www.ncbi.nlm.nih.gov/pubmed/16539675", "http://www.ncbi.nlm.nih.gov/pubmed/20178366", "http://www.ncbi.nlm.nih.gov/pubmed/14724271", "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "http://www.ncbi.nlm.nih.gov/pubmed/24413617", "http://www.ncbi.nlm.nih.gov/pubmed/18359496" ], "ideal_answer": [ "Gamma-secretase is a multisubunit enzyme complex which is consists of four proteins: presenilin 1 (PS1) or presenilin 2 (PS2), nicastrin, Aph-1 and Pen-2." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0070765", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053829" ], "type": "summary", "id": "58a2ccec60087bc10a000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Gamma-secretase is a widely expressed multisubunit enzyme complex which is involved in the pathogenesis of Alzheimer disease and hematopoietic malignancies through its aberrant processing of the amyloid precursor protein (APP) and Notch1, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20178366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Presenilin (PS1 or PS2) is the catalytic component of the gamma-secretase complex, which mediates the final proteolytic processing step leading to the Alzheimer's disease (AD)-characterizing amyloid beta-peptide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20534834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "gamma-Secretase is a membrane-embedded multi-protein complex that catalyzes the final cut of the Alzheimer's disease-related amyloid precursor protein (APP) to amyloid-beta peptides of variable length (37-43 amino acids) via an unusual intramembrane cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18359496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "The gamma-secretase complex processes substrate proteins within membranes and consists of four proteins: presenilin (PS), nicastrin, Aph-1 and Pen-2. PS harbours the enzymatic activity of the complex, and there are two mammalian PS homologues: PS1 and PS2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16135086", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 330, "text": "gamma-Secretase is known to contain four major protein constituents: presenilin (PS), nicastrin, Aph-1, and Pen-2, all of which are integral membrane proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14724271", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 893, "text": "Here we describe the association of all four components of the gamma-secretase complex, namely presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons that fulfill the criteria of lipid rafts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15322084", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1103, "text": "In contrast, the authentic TMD of NCT is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 352, "text": "Active gamma-secretase is a tetrameric protein complex consisting of presenilin-1 (or -2), nicastrin, PEN-2, and Aph-1a (or -1b).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16249316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The gamma-secretase complex processes substrate proteins within membranes and consists of four proteins: presenilin (PS), nicastrin, Aph-1 and Pen-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16135086", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 813, "text": "Maturation of exogenous NCT, gamma-secretase complex formation and proteolytic function was then investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "gamma-Secretase complexes containing N- and C-terminal fragments of different presenilin origin retain normal gamma-secretase activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16135086", "endSection": "title" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1419, "text": "Co-overexpression of presenilin-1 or APH-1 abrogated gamma-secretase inhibition probably through prevention of the incorporation of CRB2 into the gamma-secretase complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20299451", "endSection": "abstract" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1640, "text": "We conclude that a PS1/Pen2/Aph1a trimeric complex is an active enzyme, displaying biochemical properties similar to those of gamma-secretase and roughly 50% of its activity when normalized to PS1 N-terminal fragment levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20130175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "\u03b3-Secretase is involved in the regulated intramembrane proteolysis of amyloid-\u03b2 protein precursor (A\u03b2PP) and of many other important physiological substrates. \u03b3-secretase is a multiproteic complex made of four main core components, namely presenilin 1 or 2, APH-1, PEN-2, and Nicastrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24413617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Amyloid precursor protein associates with a nicastrin-dependent docking site on the presenilin 1-gamma-secretase complex in cells demonstrated by fluorescence lifetime imaging.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12805296", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Activity-dependent isolation of the presenilin- gamma -secretase complex reveals nicastrin and a gamma substrate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11867728", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Characterization of the reconstituted gamma-secretase complex from Sf9 cells co-expressing presenilin 1, nicastrin [correction of nacastrin], aph-1a, and pen-2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15766275", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "p53-Dependent Aph-1 and Pen-2 anti-apoptotic phenotype requires the integrity of the gamma-secretase complex but is independent of its activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17276981", "endSection": "title" }, { "offsetInBeginSection": 618, "offsetInEndSection": 820, "text": "Here we show that all known gamma-secretase complexes are active in APP processing and that all combinations of APH-1 variants with either FAD mutant PS1 or PS2 support pathogenic Abeta(42) production. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560791", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 629, "text": "To characterize the functional similarity between complexes of various PS composition, we analysed PS1, PS2, and chimeric PS composed of the NTF from PS1 and CTF from PS2, or vice versa, in assembly and function of the gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16135086", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 475, "text": "While beta-secretase is a classical aspartyl protease, gamma-secretase activity is associated with a high molecular weight complex. One of the complex components, which is critically required for gamma-secretase activity is nicastrin (NCT). Here we investigate the assembly of NCT into the gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 1103, "text": "Maturation of exogenous NCT, gamma-secretase complex formation and proteolytic function was then investigated. This revealed that the cytoplasmic tail of NCT is dispensable for gamma-secretase complex assembly and function. In contrast, the authentic TMD of NCT is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1103, "text": "This revealed that the cytoplasmic tail of NCT is dispensable for gamma-secretase complex assembly and function. In contrast, the authentic TMD of NCT is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 401, "text": "While beta-secretase is a classical aspartyl protease, gamma-secretase activity is associated with a high molecular weight complex. One of the complex components, which is critically required for gamma-secretase activity is nicastrin (NCT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1237, "text": "This revealed that the cytoplasmic tail of NCT is dispensable for gamma-secretase complex assembly and function. In contrast, the authentic TMD of NCT is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex. Neither soluble NCT lacking any membrane anchor nor NCT containing a heterologous TMD were inserted into the gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 1237, "text": "In contrast, the authentic TMD of NCT is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex. Neither soluble NCT lacking any membrane anchor nor NCT containing a heterologous TMD were inserted into the gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 926, "text": "Maturation of exogenous NCT, gamma-secretase complex formation and proteolytic function was then investigated. This revealed that the cytoplasmic tail of NCT is dispensable for gamma-secretase complex assembly and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 475, "text": "Here we investigate the assembly of NCT into the gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602727", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1420, "text": "Co-overexpression of presenilin-1 or APH-1 abrogated gamma-secretase inhibition probably through prevention of the incorporation of CRB2 into the gamma-secretase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20299451", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1401, "text": "This could be demonstrated also in cell-free assays, where in addition presenilin-1, the catalytic subunit of the gamma-secretase complex, was shifted out of lipid rafts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18359496", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1096, "text": "In PS1(-/-)/PS2(-/-) and NCT(-/-) fibroblasts, gamma-secretase components that still remain fail to become detergent-resistant, suggesting that raft association requires gamma-secretase complex assembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15322084", "endSection": "abstract" } ] }, { "body": "List kinases that phosphorylates the protein Bora.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24675888", "http://www.ncbi.nlm.nih.gov/pubmed/25803405", "http://www.ncbi.nlm.nih.gov/pubmed/23442801", "http://www.ncbi.nlm.nih.gov/pubmed/27831827", "http://www.ncbi.nlm.nih.gov/pubmed/26038951" ], "ideal_answer": [ "During cell division Bora becomes multiply phosphorylated by a variety of cell cycle kinases, including Aurora A and Plk1, and GSK3\u03b2 and Cdk1 albeit at distinctive sites." ], "exact_answer": [ [ "Cdk1" ], [ "Plk1" ], [ "Aurora A" ], [ "GSK3\u03b2" ] ], "type": "list", "id": "58a80bc838c171fb5b000001", "snippets": [ { "offsetInBeginSection": 1009, "offsetInEndSection": 1160, "text": "During cell division Bora becomes multiply phosphorylated by a variety of cell cycle kinases, including Aurora A and Plk1, albeit at distinctive sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25803405", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1010, "text": "Likewise, we find that phosphorylation of Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A suggesting that this mechanism is conserved in humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26038951", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 500, "text": "we show that the master mitotic kinase Cdk1 contributes to Plk1 activation through SPAT-1/Bora phosphorylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27831827", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1187, "text": "the potential role of Bora phosphorylation by Cdk1 in this process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27831827", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 754, "text": "phosphorylation of Bora on the Cdk consensus site T52 blocks Bora degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675888", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 504, "text": "Here, we used the LC-MS/MS phosphopeptide mapping assay to identify 13 in vivo hBora phosphorylation sites and characterized that GSK3\u03b2 can interact with hBora and phosphorylate hBora at Ser274 and Ser278.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23442801", "endSection": "abstract" } ] }, { "body": "Are deletions of chromosomal regulatory boundaries associated with congenital disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25315429" ], "ideal_answer": [ "Yes. Enhancer adoption caused by deletions of regulatory boundaries may contribute to a substantial minority of copy-number variation phenotypes and should thus be taken into account in their medical interpretation." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002872", "http://www.disease-ontology.org/api/metadata/DOID:1086", "http://www.disease-ontology.org/api/metadata/DOID:0080014" ], "type": "yesno", "id": "587f56c392a5b8ad44000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Deletions of chromosomal regulatory boundaries are associated with congenital disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315429", "endSection": "title" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1638, "text": "Our results suggest that enhancer adoption caused by deletions of regulatory boundaries may contribute to a substantial minority of copy-number variation phenotypes and should thus be taken into account in their medical interpretation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Deletions of chromosomal regulatory boundaries are associated with congenital disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315429", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Deletions of chromosomal regulatory boundaries are associated with congenital disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315429", "endSection": "title" } ] }, { "body": "What is the role of the UBC9 enzyme in the protein sumoylation pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24991007", "http://www.ncbi.nlm.nih.gov/pubmed/23078246", "http://www.ncbi.nlm.nih.gov/pubmed/25311713", "http://www.ncbi.nlm.nih.gov/pubmed/23628505", "http://www.ncbi.nlm.nih.gov/pubmed/16862185", "http://www.ncbi.nlm.nih.gov/pubmed/20800867", "http://www.ncbi.nlm.nih.gov/pubmed/23708104", "http://www.ncbi.nlm.nih.gov/pubmed/18617892", "http://www.ncbi.nlm.nih.gov/pubmed/19323834", "http://www.ncbi.nlm.nih.gov/pubmed/21518767", "http://www.ncbi.nlm.nih.gov/pubmed/21390240", "http://www.ncbi.nlm.nih.gov/pubmed/25097219", "http://www.ncbi.nlm.nih.gov/pubmed/20865051", "http://www.ncbi.nlm.nih.gov/pubmed/21510985", "http://www.ncbi.nlm.nih.gov/pubmed/25637535", "http://www.ncbi.nlm.nih.gov/pubmed/26582473", "http://www.ncbi.nlm.nih.gov/pubmed/26889037", "http://www.ncbi.nlm.nih.gov/pubmed/23097446", "http://www.ncbi.nlm.nih.gov/pubmed/17698038", "http://www.ncbi.nlm.nih.gov/pubmed/26826302", "http://www.ncbi.nlm.nih.gov/pubmed/23381475", "http://www.ncbi.nlm.nih.gov/pubmed/19826484", "http://www.ncbi.nlm.nih.gov/pubmed/23187003", "http://www.ncbi.nlm.nih.gov/pubmed/22525038", "http://www.ncbi.nlm.nih.gov/pubmed/21444718", "http://www.ncbi.nlm.nih.gov/pubmed/15546615", "http://www.ncbi.nlm.nih.gov/pubmed/11867732", "http://www.ncbi.nlm.nih.gov/pubmed/27142163", "http://www.ncbi.nlm.nih.gov/pubmed/20561671", "http://www.ncbi.nlm.nih.gov/pubmed/25191977", "http://www.ncbi.nlm.nih.gov/pubmed/15087395", "http://www.ncbi.nlm.nih.gov/pubmed/21278366", "http://www.ncbi.nlm.nih.gov/pubmed/22904261", "http://www.ncbi.nlm.nih.gov/pubmed/27425617" ], "ideal_answer": [ "The small ubiquitin-like modifier (SUMO) pathway in eukaryotes is an essential post-translational modification required for a variety of cellular processes, development and organelle biogenesis. SUMO-conjugating enzyme (Ubc9) is the sole conjunction enzyme in the SUMO pathway." ], "exact_answer": [ "SUMO-conjugating enzyme" ], "concepts": [ "http://www.uniprot.org/uniprot/UBC9_CHICK", "http://amigo.geneontology.org/amigo/term/GO:0016925", "http://www.uniprot.org/uniprot/UBC9_XENLA", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058207", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.uniprot.org/uniprot/UBC9_ARATH", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025841", "http://www.uniprot.org/uniprot/UBC9_YEAST", "http://www.uniprot.org/uniprot/UBC9_SCHPO", "http://www.uniprot.org/uniprot/UBC9_HUMAN", "http://www.uniprot.org/uniprot/UBC9_DICDI", "http://www.uniprot.org/uniprot/UBC9_MESAU", "http://www.uniprot.org/uniprot/UBC9_ICTTR", "http://www.uniprot.org/uniprot/UBC9_MOUSE" ], "type": "factoid", "id": "58a5b1fe60087bc10a000024", "snippets": [ { "offsetInBeginSection": 117, "offsetInEndSection": 335, "text": "Among the proteins involved in the sumoylation pathway, Ubc9 is the sole E2-conjugating enzyme required for sumoylation and plays a central role by interacting with almost all of the partners required for sumoylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191977", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1032, "text": "We also found a marked rise in levels of Ubc9, the only SUMO conjugation enzyme identified so far. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23078246", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 279, "text": "Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in sumoylation-mediated cellular pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23708104", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1166, "text": "We observed steady-state expression of SUMO1-3, SUMO-conjugated enzyme-UBC9 and deSUMOylating enzymes - SENPs, throughout normal gestation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "The small ubiquitin-like modifier (SUMO) pathway in eukaryotes is an essential post-translational modification required for a variety of cellular processes, development and organelle biogenesis. SUMO-conjugating enzyme (Ubc9) is an important conjunction enzyme in the SUMO pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525038", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1669, "text": "Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1), Ubc9 (the only known conjugating enzyme for the sumoylation pathway) or HIF-1\u03b1, augmented sumoylation of HIF-1\u03b1, nucleus-bound translocation and enhanced transcriptional activity of HIF-1\u03b1 in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21390240", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 333, "text": "Among the proteins involved in the sumoylation pathway, Ubc9 is the sole E2-conjugating enzyme required for sumoylation and plays a central role by interacting with almost all of the partners required for sumoylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191977", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 436, "text": "UBC9 is the only E2 conjugating enzyme involved in this process, and loss of UBC9 completely abolishes the SUMOylation pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27425617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Here we have identified host cell proteins involved with the cellular SUMOylation pathway, SUMO-1 (small ubiquitin-like modifier) and UBC9, a SUMO-1 conjugating enzyme that interact with classical swine fever virus (CSFV) Core protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20800867", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 278, "text": "Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in sumoylation-mediated cellular pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23708104", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 573, "text": "In this study, we found that the SUMOylation pathway was involved in the DENV life cycle, since DENV replication was reduced by silencing the cellular gene Ubc9, which encodes the sole E2-conjugating enzyme required for SUMOylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26889037", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 349, "text": "Here we demonstrate that the synaptic diffusion of Ubc9, the sole conjugating enzyme of the sumoylation pathway, is regulated by synaptic activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25311713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "The SUMO pathway parallels the classical ubiquitinylation pathway with three discrete steps: activation involving the enzyme E1, conjugation involving the E2 enzyme UBC9, and substrate modification through the cooperative association of UBC9 and E3 ligases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15546615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel target for sumoylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17698038", "endSection": "title" }, { "offsetInBeginSection": 117, "offsetInEndSection": 334, "text": "Among the proteins involved in the sumoylation pathway, Ubc9 is the sole E2-conjugating enzyme required for sumoylation and plays a central role by interacting with almost all of the partners required for sumoylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191977", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 273, "text": "Although there are multiple E2 enzymes required for ubiquitination, there is only one E2-conjugating enzyme for sumoylation, which is Ubc9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20561671", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 709, "text": "Consistent with a role of sumoylation in inhibiting Tec1 activity, specifically increasing sumoylation of Tec1 by fusing it to the sumoylating enzyme Ubc9 leads to a dramatic decrease of Tec1 transcriptional activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19826484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Ubc9 is an E2-conjugating enzyme required for sumoylation and has been implicated in regulating several critical cellular pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15087395", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1132, "text": "We also exposed placental explants to hypoxia to study the effect on the SUMOylation pathway.We observed steady-state expression of SUMO1-3, SUMO-conjugated enzyme-UBC9 and deSUMOylating enzymes - SENPs, throughout normal gestation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "It has been reported that ubiquitin-conjugating enzyme 9 (Ubc9), the unique enzyme2 in the sumoylation pathway, is up-regulated in many cancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23187003", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 333, "text": "Among the proteins involved in the sumoylation pathway, Ubc9 is the sole E2-conjugating enzyme required for sumoylation and plays a central role by interacting with almost all of the partners required for sumoylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191977", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 349, "text": "Here we demonstrate that the synaptic diffusion of Ubc9, the sole conjugating enzyme of the sumoylation pathway, is regulated by synaptic activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25311713", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 416, "text": "Here, we investigated inhibition of sumoylation as a novel antifibrotic approach.Sumoylation was inhibited by siRNA-mediated knockdown of the Small Ubiquitin-like MOdifiers (SUMO) E2-conjugating enzyme Ubc9, which is essential for sumoylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22904261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Here we have identified host cell proteins involved with the cellular SUMOylation pathway, SUMO-1 (small ubiquitin-like modifier) and UBC9, a SUMO-1 conjugating enzyme that interact with classical swine fever virus (CSFV) Core protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20800867", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 566, "text": "A new pathway that contributes to mutant CFTR degradation is mediated by the small heat shock protein, Hsp27, which cooperates with Ubc9, the E2 enzyme for SUMOylation, to selectively conjugate mutant CFTR with SUMO-2/3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26582473", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 749, "text": "Using transfection of Ets-1 wildtype (WT) or its sumoylation deficient version (Ets-1 K15R/K227R), as well as WT or mutant proteins of the SUMO pathway, we further demonstrated that the E2 SUMO-conjugating enzyme Ubc9 and a E3 SUMO ligase, PIASy, can enhance Ets-1 sumoylation, while a SUMO protease, SENP1, can desumoylate Ets-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16862185", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 863, "text": "The results show that basal SUMO modification is required for stimuli-induced p100 phosphorylation and that blocking SUMOylation of p100, either by site-directed mutation or by short interfering RNA-targeted diminution of E2 SUMO-conjugating enzyme Ubc9, inhibits various physiological stimuli-induced p100 processing and ultimate activation of the alternative NF-kappaB pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18617892", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 482, "text": "Sumoylation proceeds via an enzymatic pathway that is mechanistically analogous to ubiquitination, but requires a different E1-activating enzyme and Ubc9, a SUMO-specific E2-conjugating enzyme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11867732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "SUMO-conjugating enzyme E2 UBC9 mediates viral immediate-early protein SUMOylation in crayfish to facilitate reproduction of white spot syndrome virus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23097446", "endSection": "title" }, { "offsetInBeginSection": 526, "offsetInEndSection": 695, "text": "OBJECTIVE: To determine the role of ubiquitin-conjugating enzyme 9 (UBC9), a small ubiquitin-like modifier-conjugating enzyme, in cardiomyocyte protein quality control. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25097219", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 695, "text": "Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays a key role in tumorigenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23381475", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 438, "text": "UBC9 is the only E2 conjugating enzyme involved in this process, and loss of UBC9 completely abolishes the SUMOylation pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27425617", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 350, "text": "Here we demonstrate that the synaptic diffusion of Ubc9, the sole conjugating enzyme of the sumoylation pathway, is regulated by synaptic activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25311713", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 483, "text": "Sumoylation proceeds via an enzymatic pathway that is mechanistically analogous to ubiquitination, but requires a different E1-activating enzyme and Ubc9, a SUMO-specific E2-conjugating enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11867732", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1624, "text": "Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1), Ubc9 (the only known conjugating enzyme for the sumoylation pathway) or HIF-1\u03b1, augmented sumoylation of HIF-1\u03b1, nucleus-bound translocation and enhanced transcriptional activity of HIF-1\u03b1 in RVLM neurons took place preferentially during the pro-life phase of experimental brain death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21390240", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 575, "text": "In this study, we found that the SUMOylation pathway was involved in the DENV life cycle, since DENV replication was reduced by silencing the cellular gene Ubc9, which encodes the sole E2-conjugating enzyme required for SUMOylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26889037", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 311, "text": "In this study, we revisited the role of Tax SUMOylation using a strategy based on the targeting of Ubc9, the unique E2 SUMO-conjugating enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991007", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1155, "text": "Taken together, these findings provide evidence for regulated sumoylation as a mechanism to modulate the activity of Tec1 and validate Ubc9 fusion-directed sumoylation as a useful approach for studying protein sumoylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19826484", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 518, "text": "We report that the high risk HPVE6 proteins reduce the intracellular quantity of the sole SUMO conjugation enzyme, Ubc9, concomitant with decreased host sumoylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21510985", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1135, "text": "We observed steady-state expression of SUMO1-3, SUMO-conjugated enzyme-UBC9 and deSUMOylating enzymes - SENPs, throughout normal gestation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "As the sole E2 enzyme for SUMOylation, Ubc9 is predominantly nuclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25637535", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 397, "text": "Expression of small ubiquitin-like modifier (SUMO) molecules, SUMO E1 activating enzymes SAE1 and SAE2, SUMO E2 conjugating enzyme UBC9, and de-sumoylation enzyme sentrin/SUMO-specific proteases (SENP)1 was immunolocalized in rat intervertebral disc (IVD) cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26826302", "endSection": "abstract" } ] }, { "body": "Can the Micro-C XL method achieve mononucleosome resolution?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27723753" ], "ideal_answer": [ "Yes. Micro-C XL is an improved method for analysis of chromosome folding at mononucleosome resolution." ], "exact_answer": "yes", "type": "yesno", "id": "587dfde9ae05ffb474000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723753", "endSection": "title" }, { "offsetInBeginSection": 413, "offsetInEndSection": 538, "text": "Micro-C XL provides a single assay to interrogate chromosome folding at length scales from the nucleosome to the full genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723753", "endSection": "abstract" } ] }, { "body": "Can Diabetes be caused by a defect in a potassium chanel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25931474", "http://www.ncbi.nlm.nih.gov/pubmed/24827651", "http://www.ncbi.nlm.nih.gov/pubmed/15746700", "http://www.ncbi.nlm.nih.gov/pubmed/27118464" ], "ideal_answer": [ "Mutations in the KATP channel can lead to neonatal diabetes.", "Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016640", "http://www.disease-ontology.org/api/metadata/DOID:11717", "http://www.disease-ontology.org/api/metadata/DOID:9351", "http://www.biosemantics.org/jochem#4277521", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011188", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011189", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4277521", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003923", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003922", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003921", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024681", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015221" ], "type": "yesno", "id": "58a0a28a78275d0c4a000051", "snippets": [ { "offsetInBeginSection": 146, "offsetInEndSection": 306, "text": "Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27118464", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 472, "text": "To date, all patients affected by neonatal diabetes due to a mutation in the pore-forming subunit of the channel (Kir6.2, KCNJ11) are heterozygous for the mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27118464", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 571, "text": "e report the first clinical case of neonatal diabetes caused by a homozygous KCNJ11 mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27118464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Diffuse congenital hyperinsulinism in infancy (CHI-D) arises from mutations inactivating the KATP channel;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25931474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "We report a case of a 6-week-old infant with diabetes mellitus based on a genetic defect in the sulfonylurea receptor 1 (SUR1), an ATP-sensitive potassium (KATP) channel protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24827651", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1150, "text": "In diabetes, vascular KATP channel function is impaired.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15746700", "endSection": "abstract" } ] }, { "body": "Which fimA genotypes are associated with disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22549664", "http://www.ncbi.nlm.nih.gov/pubmed/20219603", "http://www.ncbi.nlm.nih.gov/pubmed/22466890", "http://www.ncbi.nlm.nih.gov/pubmed/23264452", "http://www.ncbi.nlm.nih.gov/pubmed/26387644", "http://www.ncbi.nlm.nih.gov/pubmed/22053966", "http://www.ncbi.nlm.nih.gov/pubmed/23646850", "http://www.ncbi.nlm.nih.gov/pubmed/24466164", "http://www.ncbi.nlm.nih.gov/pubmed/26937292", "http://www.ncbi.nlm.nih.gov/pubmed/26600627" ], "ideal_answer": [ "FimA has been characterized as an important virulence factor for P. gingivalis, and many studies, both animal experiments and clinical investigations, have characterized fimA genotypes II, Ib, and IV to be associated with disease (periodontitis and cardiovascular disease)" ], "exact_answer": [ [ "genotypes II" ], [ "genotypes Ib" ], [ "genotypes IV" ] ], "type": "list", "id": "58a94483ee23e0236b000003", "snippets": [ { "offsetInBeginSection": 476, "offsetInEndSection": 750, "text": " FimA has been characterized as an important virulence factor for P. gingivalis, and many studies, both animal experiments and clinical investigations, have characterized fimA genotypes II, Ib, and IV to be associated with disease (periodontitis and cardiovascular disease) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26387644", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 179, "text": "Long fimbriae (FimA) are important virulence factors of Porphyromonas gingivalis. Based on the diversity of the fimA gene, this species is classified into 6 genotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219603", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 1066, "text": " In cases of chronic apical periodontitis, P. gingivalis variant type IV was the most prevalent (24%), followed by types I (20%), II (16%), and III (8%). In acute abscess samples, variant type II was the most prevalent (12%), followed by types III and IV (8% of each) and type I (4%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20219603", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1082, "text": "We show that P. gingivalis strains with genotype I and II of FimA are efficient in interaction with saliva or S. gordonii. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22053966", "endSection": "abstract" }, { "offsetInBeginSection": 1238, "offsetInEndSection": 1435, "text": "A strong association between Porphyromonas gingivalis fimA genotypes II and Ib and chronic periodontitis exists in the Spanish population. The most prevalent genotype in periodontal patients is II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22549664", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1206, "text": "Our results suggest that the presence of P. gingivalis is associated with periodontal diseases, and that the type II, IV and Ib/II combination are the most common among fimA genotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22466890", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1361, "text": "Statistical analysis, however, revealed that a more significant correlation was found between periodontitis and the occurrence of type Ib fimA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23264452", "endSection": "abstract" }, { "offsetInBeginSection": 1667, "offsetInEndSection": 1755, "text": " Type II of fimA was the most prevalent genotype of P. gingivalis in patients with AgP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23646850", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1409, "text": "The population of Tregs further decreased in patients with type II FimA compared with the other types. P.gingivlias FimA genotype II was the dominant type associated with decreased Treg population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24466164", "endSection": "abstract" }, { "offsetInBeginSection": 1099, "offsetInEndSection": 1220, "text": "A trend toward a greater frequency of FimA II genotype in patients with moderate and severe periodontitis was determined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26600627", "endSection": "abstract" }, { "offsetInBeginSection": 1251, "offsetInEndSection": 1441, "text": "The fimA type Ib genotype of P. gingivalis was found to play a critical role in the destruction of peri-implant tissue, suggesting that it may be a distinct risk factor for peri-implantitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26937292", "endSection": "abstract" } ] }, { "body": "Is rucaparib used for ovarian cancer treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24962512", "http://www.ncbi.nlm.nih.gov/pubmed/27141070", "http://www.ncbi.nlm.nih.gov/pubmed/27087632", "http://www.ncbi.nlm.nih.gov/pubmed/27940438", "http://www.ncbi.nlm.nih.gov/pubmed/26281686", "http://www.ncbi.nlm.nih.gov/pubmed/27716873", "http://www.ncbi.nlm.nih.gov/pubmed/27702817", "http://www.ncbi.nlm.nih.gov/pubmed/27908594", "http://www.ncbi.nlm.nih.gov/pubmed/27002934", "http://www.ncbi.nlm.nih.gov/pubmed/27141062", "http://www.ncbi.nlm.nih.gov/pubmed/27022037", "http://www.ncbi.nlm.nih.gov/pubmed/23729402" ], "ideal_answer": [ "Yes, rucaparib is a PARP inhibitor that is used for ovarian cancer treatment." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4001", "http://www.disease-ontology.org/api/metadata/DOID:2394", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024221" ], "type": "yesno", "id": "588485bbe56acf517600000b", "snippets": [ { "offsetInBeginSection": 1323, "offsetInEndSection": 1607, "text": "While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27141062", "endSection": "abstract" }, { "offsetInBeginSection": 1219, "offsetInEndSection": 1359, "text": "Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27141070", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1840, "text": "IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has recently received approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) likely to be approved in the near future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27022037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Ovarian Cancers Harbour Defects in Non-Homologous End Joining Resulting in Resistance to Rucaparib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27702817", "endSection": "title" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1413, "text": "There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27716873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27908594", "endSection": "title" }, { "offsetInBeginSection": 3353, "offsetInEndSection": 3757, "text": "INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27908594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Genomic LOH May Predict Rucaparib Response in Ovarian Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940438", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "title" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1600, "text": "While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27141062", "endSection": "abstract" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1762, "text": "These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 704, "text": "Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27087632", "endSection": "abstract" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1771, "text": "These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 650, "text": "Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes.PURPOSE: We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.RESULTS: In vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24962512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "abstract" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1805, "text": "These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.\u00a92013 AACR\u00a92013 AACRG in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24168007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Muenke syndrome caused by point mutation (C749G) in the FGFR3 gene affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24448525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Phenotypic variability in two families of Muenke syndrome with FGFR3 mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705944", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "PURPOSE: There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24686979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378035", "endSection": "title" }, { "offsetInBeginSection": 331, "offsetInEndSection": 591, "text": "To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 733, "text": "We show in this study that knock-in mice harboring the mutation responsible for the Muenke syndrome (FgfR3(P244R)) display postnatal shortening of the cranial base along with synchondrosis growth plate dysfunction characterized by loss of resting, proliferating and hypertrophic chondrocyte zones and decreased Ihh expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22016144", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 526, "text": "Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 434, "text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "title" }, { "offsetInBeginSection": 267, "offsetInEndSection": 436, "text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The heterozygous Pro250Arg substitution mutation in fibroblast growth factor receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most common genetic cause of craniosynostosis in humans and defines Muenke syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18818193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22446440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19086028", "endSection": "abstract" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1173, "text": "In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 772, "text": "Genetic testing identifies a pathogenic mutation or chromosomal abnormality in \u223c 21% of cases, but it is likely that further causative mutations remain to be discovered.To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients with non-syndromic sagittal synostosis.Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19755431", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 819, "text": "The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11571861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Identical proline-->arginine gain-of-function mutations in fibroblast growth factor receptor (FGFR) 1 (Pro252Arg), FGFR2 (Pro253Arg) and FGFR3 (Pro250Arg), result in type I Pfeiffer, Apert and Muenke craniosynostosis syndromes, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14613973", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 435, "text": "The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21403557", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 1043, "text": "Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant amino acid change from proline to arginine at codon 250 (P250R), in keeping with Muenke syndrome (Am J Hum Genet 1997;60:555-564)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21233754", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 441, "text": "In an attempt to delineate functional features separating SCS from Muenkes syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16251895", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1237, "text": "Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10696568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 418, "text": "Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19215249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20592905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103449", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 808, "text": "METHODS: Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19755431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15241680", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 487, "text": "In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14963686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19086028", "endSection": "title" }, { "offsetInBeginSection": 410, "offsetInEndSection": 528, "text": "Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23044018", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15241680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872265", "endSection": "abstract" } ] }, { "body": "Which R package is used for visualization of linear and circular karyotypes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26791998" ], "ideal_answer": [ "The chromDraw graphical tool was developed as a user-friendly graphical tool for visualizing both linear and circular karyotypes based on the same input data matrix. The output graphics, saved in two different formats (EPS and SVG), can be easily imported to and modified in presentation and image-editing computer programs. The tool is freely distributed under GNU General Public License (GPL) and can be installed from Bioconductor or from the chromDraw home page.", "The chromDraw graphical tool was developed as a user-friendly graphical tool for visualizing both linear and circular karyotypes based on the same input data matrix. The tool is freely distributed under GNU General Public License (GPL) and can be installed from Bioconductor or from the chromDraw home page." ], "exact_answer": [ "chromDraw" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059785" ], "type": "factoid", "id": "588f2de394c1512c50000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "chromDraw: an R package for visualization of linear and circular karyotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26791998", "endSection": "title" }, { "offsetInBeginSection": 470, "offsetInEndSection": 936, "text": "The chromDraw graphical tool was developed as a user-friendly graphical tool for visualizing both linear and circular karyotypes based on the same input data matrix. The output graphics, saved in two different formats (EPS and SVG), can be easily imported to and modified in presentation and image-editing computer programs. The tool is freely distributed under GNU General Public License (GPL) and can be installed from Bioconductor or from the chromDraw home page.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26791998", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 632, "text": "The chromDraw graphical tool was developed as a user-friendly graphical tool for visualizing both linear and circular karyotypes based on the same input data matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26791998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "chromDraw: an R package for visualization of linear and circular karyotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26791998", "endSection": "title" }, { "offsetInBeginSection": 470, "offsetInEndSection": 635, "text": "The chromDraw graphical tool was developed as a user-friendly graphical tool for visualizing both linear and circular karyotypes based on the same input data matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26791998", "endSection": "abstract" } ] }, { "body": "Has small pox been eradicated from the world?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22566811", "http://www.ncbi.nlm.nih.gov/pubmed/11808015", "http://www.ncbi.nlm.nih.gov/pubmed/10742580", "http://www.ncbi.nlm.nih.gov/pubmed/14969309", "http://www.ncbi.nlm.nih.gov/pubmed/23436190", "http://www.ncbi.nlm.nih.gov/pubmed/12822115", "http://www.ncbi.nlm.nih.gov/pubmed/7013291", "http://www.ncbi.nlm.nih.gov/pubmed/11503361", "http://www.ncbi.nlm.nih.gov/pubmed/22185830" ], "ideal_answer": [ "smallpox is now eradicated.", "Yes, small pox has been eradicated.", "smallpox is now eradicated", "small pox has been eradicated." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8736", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012899", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012900" ], "type": "yesno", "id": "58a1da4e78275d0c4a000059", "snippets": [ { "offsetInBeginSection": 153, "offsetInEndSection": 183, "text": "small pox has been eradicated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10742580", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 863, "text": "smallpox is now eradicated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11808015", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1144, "text": "In May 1980 the World Health Assembly in Geneva announced in solemn form the world-wide eradication of the small-pox and gave recommendations to the member countries for concluding measures concerning the small-pox vaccination, the foundation of vaccine reserves and the control of the epidemiological situation in the world.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7013291", "endSection": "abstract" }, { "offsetInBeginSection": 65, "offsetInEndSection": 182, "text": "As a result of vaccination, diseases such as polio and measles have been controlled and small pox has been eradicated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10742580", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 277, "text": "Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23436190", "endSection": "abstract" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1057, "text": "The French owe a lot to this Central Committee of Vaccine, which greatly contributed to fighting small pox and eradicating the disease finally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11503361", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 276, "text": "Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23436190", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 868, "text": "Also, the vaccine that Jenner used, which decreased the prevalence of Small Pox worldwide in his own time, and later was used to eradicate Small Pox altogether, is discussed in light of recent data..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22566811", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 760, "text": "the only known cases of smallpox happened from an outbreak in Birmingham, England caused by a laboratory accident in the year of 1979. On May the 8 th 1980 the disease was declared as eliminated from the world by the WHO (WHO-Resolution 33.33).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12822115", "endSection": "abstract" } ] }, { "body": "Where is Akkermansia muciniphila found?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25795669", "http://www.ncbi.nlm.nih.gov/pubmed/26100928" ], "ideal_answer": [ "Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals.", "RYGB led to altered relative abundances of 31 species (P\u2009<\u20090.05, q\u2009<\u20090.15) within the first 3\u00a0months, including those of Escherichia coli, Klebsiella pneumoniae, Veillonella spp., Streptococcus spp., Alistipes spp., and Akkermansia muciniphila. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia m However, faeces from the UC cohort had lower proportions of Akkermansia muciniphila and increased diversity within Clostridium cluster XIVa compared to controls.Gut fermentation of NSP and starch is diminished in patients with UC. Specific members of the microbiota such as Akkermansia muciniphila might be decreased in diabetes and when administered to murines exerted antidiabetic effects. In parallel, the antibiotic susceptibility of Akkermansia muciniphila Muc(T) strain was studied and this strain was observed by electron microscopy." ], "exact_answer": [ "Akkermansia muciniphila resides in the gastrointestinal tracts of humans and animals." ], "type": "factoid", "id": "58bc363622d300530900001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25795669", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 365, "text": "Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with body fat mass and glucose intolerance in mice, but more evidence is needed in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26100928", "endSection": "abstract" } ] }, { "body": "Is there alternative polyadenylation during zebrafish development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22722342" ], "ideal_answer": [ "Yes. There is extensive alternative polyadenylation during zebrafish development." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026723", "http://amigo.geneontology.org/amigo/term/GO:1900365", "http://amigo.geneontology.org/amigo/term/GO:1900364", "http://amigo.geneontology.org/amigo/term/GO:0006378", "http://amigo.geneontology.org/amigo/term/GO:1900363", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015027" ], "type": "yesno", "id": "58963b0278275d0c4a00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Extensive alternative polyadenylation during zebrafish development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722342", "endSection": "title" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1525, "text": "At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3' UTRs provide a resource for studying gene regulation during vertebrate development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Extensive alternative polyadenylation during zebrafish development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722342", "endSection": "title" } ] }, { "body": "Which NADPH oxidase family member requires interaction with NOXO1 for function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18929641", "http://www.ncbi.nlm.nih.gov/pubmed/15507761", "http://www.ncbi.nlm.nih.gov/pubmed/15507762", "http://www.ncbi.nlm.nih.gov/pubmed/15824103", "http://www.ncbi.nlm.nih.gov/pubmed/27540115", "http://www.ncbi.nlm.nih.gov/pubmed/23957209", "http://www.ncbi.nlm.nih.gov/pubmed/22549734", "http://www.ncbi.nlm.nih.gov/pubmed/17900370", "http://www.ncbi.nlm.nih.gov/pubmed/16329988", "http://www.ncbi.nlm.nih.gov/pubmed/17583407", "http://www.ncbi.nlm.nih.gov/pubmed/16507994", "http://www.ncbi.nlm.nih.gov/pubmed/20454568", "http://www.ncbi.nlm.nih.gov/pubmed/20609497", "http://www.ncbi.nlm.nih.gov/pubmed/23322165", "http://www.ncbi.nlm.nih.gov/pubmed/17913709", "http://www.ncbi.nlm.nih.gov/pubmed/16762923", "http://www.ncbi.nlm.nih.gov/pubmed/16911517", "http://www.ncbi.nlm.nih.gov/pubmed/26781991", "http://www.ncbi.nlm.nih.gov/pubmed/18463161" ], "ideal_answer": [ "NADPH oxidase 1 (NOX1) requires interaction with NOXO1 for function." ], "exact_answer": [ "NADPH oxidase 1", "NOX1", "nicotinamide adenine dinucleotide phosphate-oxidase 1" ], "concepts": [ "http://www.biosemantics.org/jochem#4270191", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019255", "http://www.uniprot.org/uniprot/NOXO1_MOUSE", "http://www.uniprot.org/uniprot/NOXO1_HUMAN", "http://www.uniprot.org/uniprot/NOXA1_RAT", "http://www.uniprot.org/uniprot/NOXA1_MOUSE", "http://amigo.geneontology.org/amigo/term/GO:0043020" ], "type": "factoid", "id": "58a5a51060087bc10a000021", "snippets": [ { "offsetInBeginSection": 203, "offsetInEndSection": 439, "text": "A unique member of this family, Nox1 oxidase, functions as either a canonical or hybrid system using Nox organizing subunit 1 (NoxO1) or p47(phox), respectively, the latter of which is functional in vascular smooth muscle cells (VSMC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27540115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Phosphorylation of Noxo1 at threonine 341 regulates its interaction with Noxa1 and the superoxide-producing activity of Nox1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23957209", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 329, "text": "Superoxide production by Nox1, a member of the Nox family NAPDH oxidases, requires expression of its regulatory soluble proteins Noxo1 (Nox organizer 1) and Noxa1 (Nox activator 1) and is markedly enhanced upon cell stimulation with phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23957209", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1430, "text": "Phosphorylation of Thr341 allows Noxo1 to sufficiently interact with Noxa1, an interaction that participates in Nox1 activation. Thus phosphorylation of Noxo1 at Thr341 appears to play a crucial role in PMA-elicited activation of Nox1, providing a molecular link between PKC-mediated signal transduction and Nox1-catalyzed superoxide production. Furthermore, Ser154 in Noxo1 is phosphorylated in both resting and PMA-stimulated cells, and the phosphorylation probably participates in a PMA-independent constitutive activity of Nox1. Ser154 may also be involved in protein kinase A (PKA) mediated regulation of Nox1; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23957209", "endSection": "abstract" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1612, "text": "Thus phosphorylation of Noxo1 at Thr341 and at Ser154 appears to regulate Nox1 activity in different manners.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23957209", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 529, "text": "The activity of other Nox enzymes such as gp91(phox)/Nox2 and Nox1 is known to absolutely require both an organizer protein (p47(phox) or Noxo1) andanactivatorprotein (p67(phox) or Noxa1); for the p47(phox)-dependent activation of these oxidases, treatment of cells with stimulants such as phorbol 12-myristate 13-acetate is also indispensable. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824103", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 782, "text": "Studies of cytosolic co-factors showed that the C-terminal cytoplasmic domain of NOX1 was absolutely required for activation with NOXO1 and NOXA1 and that this activity required interaction of the putative NADPH-binding region of this domain with NOXA1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15507761", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 755, "text": "Additionally, NADPH oxidase Organizer 1 (NoxO1) is shown to interact with the NADPH-binding region of Nox1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16329988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Activation of the non-phagocytic superoxide-producing NADPH oxidase Nox1, complexed with p22(phox) at the membrane, requires its regulatory soluble proteins Noxo1 and Noxa1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16762923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "NOXO1 phosphorylation on serine 154 is critical for optimal NADPH oxidase 1 assembly and activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322165", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Activation of the superoxide-producing NADPH oxidase Nox1 requires both the organizer protein Noxo1 and the activator protein Noxa1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911517", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 643, "text": "NOX1, an NADPH oxidase homologue that is most abundantly expressed in colon epithelial cells, requires the regulatory subunits NOXO1 (NOX organizing protein 1) and NOXA1 (NOX activating protein 1), as well as the flavocytochrome component p22(phox) for maximal activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20454568", "endSection": "abstract" }, { "offsetInBeginSection": 732, "offsetInEndSection": 917, "text": "Activation of Nox1, an oxidase that is likely involved in host defence at the colon, requires novel proteins homologous to p47phox and p67phox, designated Noxo1 and Noxa1, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15507762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Molecular interaction of NADPH oxidase 1 with betaPix and Nox Organizer 1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16329988", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Reactive oxygen species (ROS) production by NADPH oxidase 1 (NOX1), which is mainly expressed in colon epithelial cells, requires the membrane-bound component p22(PHOX) and the cytosolic partners NOX organizer 1 (NOXO1), NOX activator 1 (NOXA1), and Rac1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322165", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 642, "text": "NOX1, an NADPH oxidase homologue that is most abundantly expressed in colon epithelial cells, requires the regulatory subunits NOXO1 (NOX organizing protein 1) and NOXA1 (NOX activating protein 1), as well as the flavocytochrome component p22(phox) for maximal activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20454568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Activation of the superoxide-producing NADPH oxidase Nox1 requires both the organizer protein Noxo1 and the activator protein Noxa1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Activation of the non-phagocytic superoxide-producing NADPH oxidase Nox1, complexed with p22(phox) at the membrane, requires its regulatory soluble proteins Noxo1 and Noxa1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16762923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "NADPH oxidase 1 (Nox1) is a multicomponent enzyme consisting of p22(phox), Nox organizer 1 (NOXO1), Nox1 activator 1, and Rac1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18929641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "UNLABELLED: Superoxide production by Nox1, a member of the Nox family NAPDH oxidases, requires expression of its regulatory soluble proteins Noxo1 (Nox organizer 1) and Noxa1 (Nox activator 1) and is markedly enhanced upon cell stimulation with phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23957209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22549734", "endSection": "title" }, { "offsetInBeginSection": 532, "offsetInEndSection": 785, "text": "Studies of cytosolic co-factors showed that the C-terminal cytoplasmic domain of NOX1 was absolutely required for activation with NOXO1 and NOXA1 and that this activity required interaction of the putative NADPH-binding region of this domain with NOXA1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15507761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Nox activator 1 (NoxA1) is a homologue of p67(phox) that acts in conjunction with Nox organizer 1 (NoxO1) to regulate reactive oxygen species (ROS) production by the NADPH oxidase Nox1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17913709", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 568, "text": "Nox1 is highly expressed in the colon, and requires two cytosolic regulators, the organizer subunit NoxO1 and the activator subunit NoxA1, as well as the binding of Rac1 GTPase, for its activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20609497", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 508, "text": "Nox1 is highly expressed in the colon, and it requires two cytosolic regulators, NoxO1 and NoxA1, as well as the binding of Rac1 GTPase, for its activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463161", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Reactive oxygen species (ROS) production by NADPH oxidase 1 (NOX1), which is mainly expressed in colon epithelial cells, requires the membrane-bound component p22(PHOX) and the cytosolic partners NOX organizer 1 (NOXO1), NOX activator 1 (NOXA1), and Rac1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23322165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Superoxide production by Nox1, a member of the Nox family NAPDH oxidases, requires expression of its regulatory soluble proteins Noxo1 (Nox organizer 1) and Noxa1 (Nox activator 1) and is markedly enhanced upon cell stimulation with phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23957209", "endSection": "abstract" } ] }, { "body": "Are alterations in ultraconserved elements implicated in breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "http://www.ncbi.nlm.nih.gov/pubmed/21331621" ], "ideal_answer": [ "Yes. SNPs in ultraconserved elements (UCEs) might be associated with cancer risk." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069584", "http://www.disease-ontology.org/api/metadata/DOID:0060548", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061325", "http://www.disease-ontology.org/api/metadata/DOID:1612", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000072656", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050436", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058922", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001940", "http://www.disease-ontology.org/api/metadata/DOID:14521", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018567", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064726" ], "type": "yesno", "id": "587e276be96a600607000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "SNPs in ultraconserved elements and familial breast cancer risk", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "endSection": "title" }, { "offsetInBeginSection": 639, "offsetInEndSection": 822, "text": " In the present study, we investigated the influence of six SNPs within UCEs on familial breast cancer risk. Two out of six SNPs showed an association with familial breast cancer risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "endSection": "abstract" }, { "offsetInBeginSection": 1456, "offsetInEndSection": 1545, "text": "This is the first study indicating that SNPs in UCEs might be associated with cancer risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "SNPs in ultraconserved elements and familial breast cancer risk.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "endSection": "title" }, { "offsetInBeginSection": 103, "offsetInEndSection": 244, "text": "Recent studies have indicated that UCEs are not mutation cold regions and likely to be concerned with cancers, including breast cancer (BC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "SNPs in ultraconserved elements and familial breast cancer risk.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174240", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Genetic variants in ultraconserved elements and risk of breast cancer in Chinese population.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331621", "endSection": "title" } ] }, { "body": "What is the mechanism of action of Osimertinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27861144", "http://www.ncbi.nlm.nih.gov/pubmed/27393507", "http://www.ncbi.nlm.nih.gov/pubmed/27923714", "http://www.ncbi.nlm.nih.gov/pubmed/26902828", "http://www.ncbi.nlm.nih.gov/pubmed/27169328", "http://www.ncbi.nlm.nih.gov/pubmed/27660466", "http://www.ncbi.nlm.nih.gov/pubmed/27835594", "http://www.ncbi.nlm.nih.gov/pubmed/27912836", "http://www.ncbi.nlm.nih.gov/pubmed/26620497", "http://www.ncbi.nlm.nih.gov/pubmed/27885838", "http://www.ncbi.nlm.nih.gov/pubmed/27196753", "http://www.ncbi.nlm.nih.gov/pubmed/26515464", "http://www.ncbi.nlm.nih.gov/pubmed/26720671", "http://www.ncbi.nlm.nih.gov/pubmed/27071706", "http://www.ncbi.nlm.nih.gov/pubmed/27649127", "http://www.ncbi.nlm.nih.gov/pubmed/26898616", "http://www.ncbi.nlm.nih.gov/pubmed/26943236" ], "ideal_answer": [ "Osimertinib is a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504" ], "type": "summary", "id": "58848822e56acf517600000c", "snippets": [ { "offsetInBeginSection": 761, "offsetInEndSection": 1004, "text": "In addition, mutations leading to resistance to first-line EGFR and ALK TKIs can now be successfully inhibited by soon to be approved third-generation EGFR TKIs (osimertinib, rociletinib) and second-generation ALK TKIs (ceritinib, alectinib). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26620497", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 598, "text": "Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27912836", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 429, "text": "Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27071706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "PURPOSE: Osimertinib (AZD9291) 80\u00a0mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902828", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 649, "text": "RECENT FINDINGS: Third-generation TKIs in clinical development include osimertinib, rociletinib, and HM61713.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26720671", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 790, "text": "In this study, we investigated the interaction between ABCB1 and osimertinib, a novel selective, irreversible third-generation EGFR TKI that has recently been approved by the U.S. Food and Drug Administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27169328", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1758, "text": "Considering that osimertinib is a clinically approved third-generation EGFR TKI, our findings suggest that a combination therapy with osimertinib and conventional anticancer drugs may be beneficial to patients with MDR tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27169328", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 682, "text": "In our study, we investigated whether osimertinib (AZD9291), a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation, could reverse MDR induced by ABCB1 and ABCG2 in vitro, in vivo, and ex vivo Our results showed that osimertinib significantly increased the sensitivity of ABCB1- and ABCG2-overexpressing cells to their substrate chemotherapeutic agents in vitro and in the model of ABCB1-overexpressing KBv200 cell xenograft in nude mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27196753", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 771, "text": "The potency of 1st (erlotinib), 2nd (afatinib) and 3rd (osimertinib and rociletinib) generation EGFR-TKIs was compared in vitro for human lung cancer cell lines and Ba/F3 cells, which exogenously express mutated or wild type EGFR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515464", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 561, "text": "Osimertinib (AZD9291, Tagrisso\u2122), an oral, third-generation EGFR TKI, has been designed to target the EGFR T790M mutation, while sparing wild-type EGFR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27660466", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1003, "text": "Early phase clinical data suggest the third generation EGFR TKIs such as osimertinib, rociletinib, and HM61713 are highly efficacious and well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26898616", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1039, "text": "We review the rapid clinical development and approval of the third-generation EGFR TKI osimertinib for treatment of NSCLCs with EGFR-T790M.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26943236", "endSection": "abstract" } ] }, { "body": "What is Bartter syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12920401", "http://www.ncbi.nlm.nih.gov/pubmed/1328936", "http://www.ncbi.nlm.nih.gov/pubmed/7842074", "http://www.ncbi.nlm.nih.gov/pubmed/18800266", "http://www.ncbi.nlm.nih.gov/pubmed/6395627", "http://www.ncbi.nlm.nih.gov/pubmed/9203176", "http://www.ncbi.nlm.nih.gov/pubmed/20127218", "http://www.ncbi.nlm.nih.gov/pubmed/7869998", "http://www.ncbi.nlm.nih.gov/pubmed/24696311", "http://www.ncbi.nlm.nih.gov/pubmed/10906158", "http://www.ncbi.nlm.nih.gov/pubmed/25810436", "http://www.ncbi.nlm.nih.gov/pubmed/9502562", "http://www.ncbi.nlm.nih.gov/pubmed/23342992", "http://www.ncbi.nlm.nih.gov/pubmed/22282380", "http://www.ncbi.nlm.nih.gov/pubmed/15875219", "http://www.ncbi.nlm.nih.gov/pubmed/21431899", "http://www.ncbi.nlm.nih.gov/pubmed/16953151", "http://www.ncbi.nlm.nih.gov/pubmed/23164417", "http://www.ncbi.nlm.nih.gov/pubmed/19915517", "http://www.ncbi.nlm.nih.gov/pubmed/15056980", "http://www.ncbi.nlm.nih.gov/pubmed/22142744", "http://www.ncbi.nlm.nih.gov/pubmed/8897553", "http://www.ncbi.nlm.nih.gov/pubmed/24377430", "http://www.ncbi.nlm.nih.gov/pubmed/27277374", "http://www.ncbi.nlm.nih.gov/pubmed/21705784" ], "ideal_answer": [ "All forms of Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism", "All forms of hereditary Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0110147", "http://www.disease-ontology.org/api/metadata/DOID:0110146", "http://www.disease-ontology.org/api/metadata/DOID:0110145", "http://www.disease-ontology.org/api/metadata/DOID:0110144", "http://www.disease-ontology.org/api/metadata/DOID:0110143", "http://www.disease-ontology.org/api/metadata/DOID:0110142", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001477", "http://www.disease-ontology.org/api/metadata/DOID:445" ], "type": "summary", "id": "58bcb83d02b8c6095300000f", "snippets": [ { "offsetInBeginSection": 199, "offsetInEndSection": 316, "text": "All forms of Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the four variants of Bartter syndrome in the genetically based nomenclature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Bartter syndrome (BS) is a hereditary disease, with an autosomal recessive or autosomal dominant mode of transmission. It is characterized by salt wasting hypochloraemic, hypokalaemic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27277374", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 345, "text": "Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2 years of life, known as classic Bartter syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23164417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23164417", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 774, "text": "Classic Bartter syndrome and neonatal Bartter syndrome have defects in genes that affect transport channels in the ascending loop of Henle, where as in Gitleman syndrome the defect occurs in the transport channels of the distal convoluted tubule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18800266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Bartter syndrome type III and congenital anomalies of the kidney and urinary tract: an antenatal presentation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23164417", "endSection": "title" }, { "offsetInBeginSection": 33, "offsetInEndSection": 129, "text": "Bartter's syndrome associated with hydramnios, prematurity, hypercalciuria and nephrocalcinosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6395627", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Bartter syndrome (BS) is a rare renal tubular disorder presenting with hypokalemic metabolic alkalosis, which is classified into five types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431899", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 977, "text": "It has been described in patients with chronic diarrhoea, eating disorders, laxative abuse and primary hyperaldosteronism; also occasionally in Bartter syndrome (BS), in which severe hypokalaemia accompanies significant renal sodium and water losses, though rarely in Gitelman syndrome (GS), in which there is equally severe hypokalaemia, but only modest sodium losses.We hypothesized that hypokalaemic nephropathy may not be due to potassium depletion per se, but persistently elevated circulating levels of aldosterone, possibly with superimposed episodes of renal hypoperfusion.We searched UK and European data sets to retrospectively compare serum and urinary parameters in patients with GS and BS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21705784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Acquired Bartter-like syndrome (BLS), characterized by hypokalemic metabolic alkalosis, hypomagnesemia, hypocalcemia, and normal kidney function, can be induced by diuretics or antibiotics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23342992", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 129, "text": "lassic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24377430", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 167, "text": "clinical features of two renal tubular disorders characterized by sodium and potassium wasting: Bartter syndrome and Gitelman syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22282380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Bartter syndrome is an autosomic recessive disease characterized by severe polyuria and sodium renal loss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19915517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The term \"Bartter syndrome\" encompasses a group of closely related inherited tubulopathies characterized by markedly reduced NaCl transport by the distal nephron. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15875219", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 353, "text": " true Bartter's syndrome, diagnosed as a normotensive, hyperreninaemic, hypokalaemic metabolic alkalosis with normal urine chloride excretion, low CH2O/(CH2O+CCl) ratio during maximal water diuresis and negative urine screen for diuretics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1328936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Bartter's syndrome belongs to a group of hypokalemic renal channel diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16953151", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 197, "text": "Hypokalemia due to renal potassium wasting in the absence of hypertension, moderate metabolic alkalosis, hyperreninism and hyperaldosteronism suggest the presence of Bartter's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7869998", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 294, "text": " Inherited hypokalemic renal tubulopathies are differentiated into at least three clinical subtypes: (1) the Gitelman variant of Bartter syndrome (GS); (2) hyperprostaglandin E syndrome, the antenatal variant of Bartter syndrome (HPS/aBS); and (3) the classic Bartter syndrome (cBS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10906158", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 306, "text": "Bartter syndrome, a group of autosomal recessive disorders that are characterized by markedly reduced or absent salt transport by the thick ascending limb of Henle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12920401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Bartter's and Gitelman's syndromes are characterized by hypokalemia, normal to low blood pressure and hypochloremic metabolic alkalosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15056980", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 217, "text": "Bartter's syndrome has been used to describe a spectrum of inherited renal tubular disorders with hypokalemic metabolic alkalosis and overlapping and additional clinical and biochemical features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8897553", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 168, "text": "antenatal variant of Bartter syndrome is characterized by a history of polyhydramnios, premature birth, metabolic alkalosis, hypokalemia, polyuria and renal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20127218", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 354, "text": "Most patients with Bartter syndrome have defects in transporters in the thick ascending limb of the loop of Henle, such as the Na-K-2Cl cotransporter, NKCC2, or the ATP-sensitive potassium channel, ROMK. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9502562", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 158, "text": "Gitelman's syndrome or familial hypokalemia-hypomagnesemia and Bartter syndrome share some common features but their prognosis is quite different.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7842074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "Bartter's and Gitelman's syndromes are two different genetic renal diseases, but are both characterised by hypokalaemia and metabolic alkalosis. Bartter's syndrome is characterised by multiple gene mutations (Na-K-2Cl cotransporter; K(+) channels renal outer medullary potassium channel (ROMK); Cl channels, chloride channel Kb (ClCNKb); regulatory protein Barttin; and Ca(2+) -sensing receptor, CaSR) at the thick ascending limb of Henle's loop, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22142744", "endSection": "abstract" } ] }, { "body": "Is there any tool that facilitates the functional analysis of cis-regulatory regions in zebrafish?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19653328" ], "ideal_answer": [ "Yes. The zebrafish enhancer detection (ZED) vector is a tool that facilitates transgenesis and the functional analysis of cis-regulatory regions in zebrafish." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004742", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011401", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015027", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012045" ], "type": "yesno", "id": "588f5e9994c1512c50000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19653328", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 1144, "text": "he cis-regulatory sequences control when, where, and how much genes are transcribed and can activate (enhancers) or repress (silencers) gene expression. Here, we describe a novel Tol2 transposon-based vector for assessing enhancer activity in the zebrafish (Danio rerio). This Zebrafish Enhancer Detector (ZED) vector harbors several key improvements, among them a sensitive and specific minimal promoter chosen for optimal enhancer activity detection, insulator sequences to shield the minimal promoter from position effects, and a positive control for transgenesis. Additionally, we demonstrate that highly conserved noncoding sequences homologous between humans and zebrafish largely with enhancer activity largely retain their tissue-specific enhancer activity during vertebrate evolution. More strikingly, insulator sequences from mouse and chicken, but not conserved in zebrafish, maintain their insulator capacity when tested in this model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19653328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19653328", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19653328", "endSection": "title" } ] }, { "body": "List RNA modifications databases", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27016142", "http://www.ncbi.nlm.nih.gov/pubmed/26464443", "http://www.ncbi.nlm.nih.gov/pubmed/23118484" ], "ideal_answer": [ "RMBase and MODOMICS" ], "exact_answer": [ [ "RMBase", "RNA Modification Base" ], [ "MODOMICS" ] ], "type": "list", "id": "58bbb71f22d3005309000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "RMBase: a resource for decoding the landscape of RNA modifications from high-throughput sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26464443", "endSection": "title" }, { "offsetInBeginSection": 366, "offsetInEndSection": 608, "text": "we developed a novel resource, RMBase (RNA Modification Base, http://mirlab.sysu.edu.cn/rmbase/), to decode the genome-wide landscape of RNA modifications identified from high-throughput modification data generated by 18 independent studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26464443", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 921, "text": " known pathways of RNA modification from the MODOMICS database", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27016142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "MODOMICS is a database of RNA modifications that provides comprehensive information concerning the chemical structures of modified ribonucleosides, their biosynthetic pathways, RNA-modifying enzymes and location of modified residues in RNA sequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23118484", "endSection": "abstract" } ] }, { "body": "Please list the 3 findings in HELLP syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15027924", "http://www.ncbi.nlm.nih.gov/pubmed/11720149", "http://www.ncbi.nlm.nih.gov/pubmed/8678146", "http://www.ncbi.nlm.nih.gov/pubmed/15572962", "http://www.ncbi.nlm.nih.gov/pubmed/23871223", "http://www.ncbi.nlm.nih.gov/pubmed/26016316", "http://www.ncbi.nlm.nih.gov/pubmed/26953551", "http://www.ncbi.nlm.nih.gov/pubmed/11854637", "http://www.ncbi.nlm.nih.gov/pubmed/23040928", "http://www.ncbi.nlm.nih.gov/pubmed/26446688", "http://www.ncbi.nlm.nih.gov/pubmed/23697398", "http://www.ncbi.nlm.nih.gov/pubmed/25806101", "http://www.ncbi.nlm.nih.gov/pubmed/21501125", "http://www.ncbi.nlm.nih.gov/pubmed/1471661", "http://www.ncbi.nlm.nih.gov/pubmed/10843242", "http://www.ncbi.nlm.nih.gov/pubmed/8765269", "http://www.ncbi.nlm.nih.gov/pubmed/9914607", "http://www.ncbi.nlm.nih.gov/pubmed/10847654", "http://www.ncbi.nlm.nih.gov/pubmed/19703145", "http://www.ncbi.nlm.nih.gov/pubmed/19663680", "http://www.ncbi.nlm.nih.gov/pubmed/17666652", "http://www.ncbi.nlm.nih.gov/pubmed/8059835" ], "ideal_answer": [ "hemolysis, elevated liver enzymes and low platelets constitute the hellp syndrome.", "HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is an obstetric complication and is characterized by microangiopathic hemolytic anemia, elevated liver enzymes by intravascular breakdown of fibrin in hepatic sinusoids and reduction of platelet circulation by its increased consumption" ], "exact_answer": [ [ "hemolytic anemia" ], [ "elevated liver enzymes" ], [ "low platlets" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13133", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017359" ], "type": "list", "id": "58bc9a5002b8c60953000008", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 374, "text": "HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is an obstetric complication with heterogonous presentation and multisystemic involvement. It is characterized by microangiopathic hemolytic anemia, elevated liver enzymes by intravascular breakdown of fibrin in hepatic sinusoids and reduction of platelet circulation by its increased consumption", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26446688", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 431, "text": "Hemolysis, elevated liver enzymes and low platelets constitute the HELLP syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26953551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Our objective was to describe the hepatic imaging findings in selected patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and to correlate these findings with the severity of concurrent clinical and laboratory abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8678146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Our objective was to categorize the histologic findings in the liver in patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and to correlate these findings with the severity of clinical laboratory abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1471661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 451, "text": "OBJECTIVE: Our purpose was to test the hypothesis that the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome is the result of excessive vasoconstriction of the hepatic arterial circulation.STUDY DESIGN: Doppler ultrasonography was used to measure the pulsatility index of the common hepatic artery in 14 women with preeclampsia, 15 with preeclampsia complicated by HELLP syndrome, and 8 with HELLP syndrome but without proteinuria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8059835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Extensive hepatic infarction in severe preeclampsia as part of the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): evolution of CT findings and successful treatment with plasma exchange therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040928", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "OBJECTIVE: Our objective was to categorize the histologic findings in the liver in patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and to correlate these findings with the severity of clinical laboratory abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1471661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) is a life threatening, severe complication of pre-eclampsia with typical laboratory findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10847654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11720149", "endSection": "title" }, { "offsetInBeginSection": 19, "offsetInEndSection": 93, "text": "hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11720149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "HELLP syndrome, a syndrome of hemolysis, elevated liver enzymes and low platelets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10843242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "HELLP syndrome is a collection of symptoms described as hemolysis, elevated liver enzymes and low platelets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25806101", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 333, "text": "The HELLP syndrome is characterized by the presence of hypertension disorder more a triad: microangiopathic hemolysis, elevated liver enzymes and low platelet count.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26016316", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 115, "text": "HELLP (hemolysis, elevated liver enzymes, and low platelets)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8765269", "endSection": "title" }, { "offsetInBeginSection": 88, "offsetInEndSection": 160, "text": " HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8765269", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 136, "text": "Hepatic hemorrhage occurs in less than 5% of patients with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23871223", "endSection": "abstract" }, { "offsetInBeginSection": 39, "offsetInEndSection": 100, "text": " HELLP (haemolysis, elevated liver enzymes and low platelets)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15027924", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 93, "text": "Hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP syndrome) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19703145", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 174, "text": " hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501125", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 90, "text": " hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome, i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19663680", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 81, "text": "Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23697398", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 144, "text": "HELLP (hemolysis, elevated liver enzymes, and low platelet count)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9914607", "endSection": "title" }, { "offsetInBeginSection": 373, "offsetInEndSection": 438, "text": "HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11854637", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 95, "text": "hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17666652", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 227, "text": "hemolysis, elevated liver enzymes, and low platelets (HELLP),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15572962", "endSection": "abstract" } ] }, { "body": "Which mutated gene is associated with Waardenburg and Tietz syndromes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10952390", "http://www.ncbi.nlm.nih.gov/pubmed/22371403", "http://www.ncbi.nlm.nih.gov/pubmed/24379252", "http://www.ncbi.nlm.nih.gov/pubmed/23098757", "http://www.ncbi.nlm.nih.gov/pubmed/22258527", "http://www.ncbi.nlm.nih.gov/pubmed/10536986", "http://www.ncbi.nlm.nih.gov/pubmed/19938076", "http://www.ncbi.nlm.nih.gov/pubmed/23787126", "http://www.ncbi.nlm.nih.gov/pubmed/20485200", "http://www.ncbi.nlm.nih.gov/pubmed/9546825", "http://www.ncbi.nlm.nih.gov/pubmed/10790403", "http://www.ncbi.nlm.nih.gov/pubmed/23020089", "http://www.ncbi.nlm.nih.gov/pubmed/23512835", "http://www.ncbi.nlm.nih.gov/pubmed/10851256", "http://www.ncbi.nlm.nih.gov/pubmed/27604145", "http://www.ncbi.nlm.nih.gov/pubmed/22196401", "http://www.ncbi.nlm.nih.gov/pubmed/26252099" ], "ideal_answer": [ "Mutations in microphthalmia-associated transcription factor (MITF) gene cause Waardenburg and Tietz syndromes." ], "exact_answer": [ "microphthalmia-associated transcription factor gene", "MITF" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051739", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014849", "http://www.uniprot.org/uniprot/MITF_HUMAN" ], "type": "factoid", "id": "58a57f9460087bc10a00001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27604145", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27604145", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1054, "text": "For example, mutations of the MITF gene cause Waardenburg syndrome type 2A as well as Tietz syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379252", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1346, "text": "For example, mutations of MITF, SNAI2 and SOX10 genes are observed in Waardenburg syndrome type II and mutations of EDNRB, EDN3 and SOX10 genes are responsible for Waardenburg syndrome type IV. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379252", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 636, "text": "These disorders are represented by Waardenburg syndrome, piebaldism and Tietz syndrome, and are caused by different mutations of various or the same genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379252", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 344, "text": "Mutations in the MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) and Tietz syndrome (TS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787126", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1342, "text": "All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512835", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1676, "text": "MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512835", "endSection": "abstract" }, { "offsetInBeginSection": 1689, "offsetInEndSection": 2048, "text": "On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype-phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum that is influenced by MITF mutation type and position.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Novel and recurrent non-truncating mutations of the MITF basic domain: genotypic and phenotypic variations in Waardenburg and Tietz syndromes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258527", "endSection": "title" }, { "offsetInBeginSection": 200, "offsetInEndSection": 487, "text": "A notable relationship has been described between non-truncating mutations of its basic domain and Tietz syndrome, which is characterized by albinoid-like hypopigmentation of the skin and hair, rather than the patchy depigmentation seen in Waardenburg syndrome, and severe hearing loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258527", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 348, "text": "Mutations in microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome type 2 (WS2), a dominantly inherited disorder involving hearing loss and pigment disturbances caused by a lack of melanocytes. On rare occasions, mutations in MITF lead to Tietz syndrome (TS), which is characterized by a severe WS2 phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20485200", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 389, "text": "In humans, haploinsufficiency of MITF causes Waardenburg syndrome type 2, while a dominant-negative mutation causes Tietz syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10952390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10851256", "endSection": "title" }, { "offsetInBeginSection": 474, "offsetInEndSection": 869, "text": "This family was reascertained and a missense mutation was found in the basic region of the MITF gene in family members with Tietz syndrome. Mutations in other regions of this gene have been found to produce Waardenburg syndrome type 2 (WS2), which also includes pigmentary changes and hearing loss, but in contrast to Tietz syndrome, depigmentation is patchy and hearing loss is variable in WS2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10851256", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 427, "text": "In humans, MITF mutations cause Waardenburg syndrome type 2A (WS2A) and Tietz syndrome, autosomal dominant disorders resulting in deafness and hypopigmentation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Mutation of the MITF gene in albinism-deafness syndrome (Tietz syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9546825", "endSection": "title" }, { "offsetInBeginSection": 260, "offsetInEndSection": 334, "text": "MITF gene mutations account for 20% of Waardenburg syndrome (WS) type II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9546825", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 343, "text": "Mutations in the MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) and Tietz syndrome (TS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 485, "text": "The microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper transcription factor, which regulates melanocyte development and the biosynthetic melanin pathway. A notable relationship has been described between non-truncating mutations of its basic domain and Tietz syndrome, which is characterized by albinoid-like hypopigmentation of the skin and hair, rather than the patchy depigmentation seen in Waardenburg syndrome, and severe hearing loss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258527", "endSection": "abstract" }, { "offsetInBeginSection": 1650, "offsetInEndSection": 1750, "text": "Mutations of the MITF gene may lead to hereditary diseases: Waardenburg type II and Tietz syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23020089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "On some occasions, mutations of a gene cause different syndromes that may have similar phenotypes. For example, mutations of the MITF gene cause Waardenburg syndrome type 2 (Tassabehji et al, 1994; Nobukuni et al, 1996) as well as Tietz syndrome (Smith et al, 1997)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10536986", "endSection": "abstract" }, { "offsetInBeginSection": 1638, "offsetInEndSection": 1738, "text": "Mutations of the MITF gene may lead to hereditary diseases: Waardenburg type II and Tietz syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22371403", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 342, "text": "Mutations in the MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) and Tietz syndrome (TS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787126", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1048, "text": "For example, mutations of the MITF gene cause Waardenburg syndrome type 2A as well as Tietz syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379252", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 265, "text": "For example, mutations of the MITF gene cause Waardenburg syndrome type 2 (Tassabehji et al, 1994; Nobukuni et al, 1996) as well as Tietz syndrome (Smith et al, 1997).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10536986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23020089", "endSection": "title" }, { "offsetInBeginSection": 527, "offsetInEndSection": 720, "text": "By analyzing the genes for Waardenburg syndrome, we showed that PAX3, the gene responsible for Waardenburg syndrome type 1, regulates MITF, the gene responsible for Waardenburg syndrome type 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10536986", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 333, "text": "MITF gene mutations account for 20% of Waardenburg syndrome (WS) type II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9546825", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 342, "text": "Mutations in the MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) and Tietz syndrome (TS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23787126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Novel and recurrent non-truncating mutations of the MITF basic domain: genotypic and phenotypic variations in Waardenburg and Tietz syndromes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258527", "endSection": "title" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1053, "text": "For example, mutations of the MITF gene cause Waardenburg syndrome type 2A as well as Tietz syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379252", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 614, "text": "This family was reascertained and a missense mutation was found in the basic region of the MITF gene in family members with Tietz syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10851256", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 348, "text": "On rare occasions, mutations in MITF lead to Tietz syndrome (TS), which is characterized by a severe WS2 phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20485200", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 267, "text": "For example, mutations of the MITF gene cause Waardenburg syndrome type 2 (Tassabehji et al, 1994; Nobukuni et al, 1996) as well as Tietz syndrome (Smith et al, 1997). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10536986", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 266, "text": "For example, mutations of the MITF gene cause Waardenburg syndrome type 2 (Tassabehji et al, 1994; Nobukuni et al, 1996) as well as Tietz syndrome (Smith et al, 1997).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10536986", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 426, "text": "In humans, MITF mutations cause Waardenburg syndrome type 2A (WS2A) and Tietz syndrome, autosomal dominant disorders resulting in deafness and hypopigmentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790403", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 388, "text": "In humans, haploinsufficiency of MITF causes Waardenburg syndrome type 2, while a dominant-negative mutation causes Tietz syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10952390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27604145", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27604145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23020089", "endSection": "title" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1345, "text": "For example, mutations of MITF, SNAI2 and SOX10 genes are observed in Waardenburg syndrome type II and mutations of EDNRB, EDN3 and SOX10 genes are responsible for Waardenburg syndrome type IV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Mutation of the MITF gene in albinism-deafness syndrome (Tietz syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9546825", "endSection": "title" } ] }, { "body": "List the three most abundant bacterial phyla present in mouse feces.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25537565", "http://www.ncbi.nlm.nih.gov/pubmed/23457582", "http://www.ncbi.nlm.nih.gov/pubmed/19159975", "http://www.ncbi.nlm.nih.gov/pubmed/20926643" ], "ideal_answer": [ "Firmicutes\nProteobacteria \nBacteroidetes" ], "exact_answer": [ [ "Firmicutes" ], [ "Proteobacteria" ], [ "Bacteroidetes" ] ], "type": "list", "id": "58bbbe6822d300530900001a", "snippets": [ { "offsetInBeginSection": 862, "offsetInEndSection": 1047, "text": "Amplicons representing the major phyla encountered in the rumen (Firmicutes, 43.7%; Proteobacteria, 28.7%; Bacteroidetes, 25.3%; Spirochea, 1.1%, and Synergistes, 1.1%) were recovered, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19159975", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 152, "text": "alterations in the gut microbiota (increased Firmicutes and decreased Bacteroidetes)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20926643", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 536, "text": "The taxonomic analysis of the metagenomic reads indicated that pygmy loris fecal microbiomes were dominated by Bacteroidetes and Proteobacteria phyla. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23457582", "endSection": "abstract" }, { "offsetInBeginSection": 1025, "offsetInEndSection": 1193, "text": "Specifically, intermittent hypoxia-exposed mice showed a higher abundance of Firmicutes and a smaller abundance of Bacteroidetes and Proteobacteria phyla than controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25537565", "endSection": "abstract" } ] }, { "body": "What gene is mutated in Sickle Cell Anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27802215", "http://www.ncbi.nlm.nih.gov/pubmed/27814292", "http://www.ncbi.nlm.nih.gov/pubmed/17662889", "http://www.ncbi.nlm.nih.gov/pubmed/1301951", "http://www.ncbi.nlm.nih.gov/pubmed/11172667", "http://www.ncbi.nlm.nih.gov/pubmed/20886046", "http://www.ncbi.nlm.nih.gov/pubmed/8745433", "http://www.ncbi.nlm.nih.gov/pubmed/6310991", "http://www.ncbi.nlm.nih.gov/pubmed/7624311" ], "ideal_answer": [ "Sickle cell anemia (SCA) is an autosomal recessive disease caused by by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis.", " sca patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene." ], "exact_answer": [ "HBB" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000755", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006451", "http://www.disease-ontology.org/api/metadata/DOID:10923", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012805" ], "type": "factoid", "id": "58bcabc702b8c6095300000e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 204, "text": "Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27802215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27814292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Sickle cell anemia is caused by a single type of mutation, a homozygous A\u2192T substitution in the \u00df globin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20886046", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 486, "text": "Implementation of this approach for disorders resulting from mutations affecting the beta-globin gene (e.g., beta-thalassemia and sickle cell anemia), however, has been hampered by the inability to generate recombinant viruses able to efficiently and faithfully transmit the necessary sequences for appropriate gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7624311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "The allele-specific PCR approach has been modified by introducing a second mismatch at the 3'-penultimate link of the primer and used to identify the sickle cell anemia mutation (A-->T transversion in the sixth codon of the human beta-globin gene causing Glu-->Val substitution in the protein), thus obviating the problem of an interpretationally ambiguous 3'-terminal mismatch including T residue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1301951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Sickle-cell anemia results from an A leads to T transversion in the second nucleotide of codon 6 of the beta-globin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6310991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Sickle cell anemia is a genetic blood disorder arising from a point mutation in the beta-globin gene that leads to the replacement of glutamic acid residue by valine at the sixth position of the beta--chain of hemoglobin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11172667", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 153, "text": "Sickle cell anemia is a genetic blood disease resulting from production of mutant beta-globin (beta(S)) and has severe clinical consequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662889", "endSection": "abstract" } ] }, { "body": "What is the function of the Indian hedgehog protein in chondrocytes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24821091", "http://www.ncbi.nlm.nih.gov/pubmed/17328886", "http://www.ncbi.nlm.nih.gov/pubmed/11517192", "http://www.ncbi.nlm.nih.gov/pubmed/11850620", "http://www.ncbi.nlm.nih.gov/pubmed/10328918", "http://www.ncbi.nlm.nih.gov/pubmed/12213208", "http://www.ncbi.nlm.nih.gov/pubmed/12745383", "http://www.ncbi.nlm.nih.gov/pubmed/17907424", "http://www.ncbi.nlm.nih.gov/pubmed/21795282", "http://www.ncbi.nlm.nih.gov/pubmed/25028519", "http://www.ncbi.nlm.nih.gov/pubmed/19906842", "http://www.ncbi.nlm.nih.gov/pubmed/18434416", "http://www.ncbi.nlm.nih.gov/pubmed/10615989", "http://www.ncbi.nlm.nih.gov/pubmed/11332615", "http://www.ncbi.nlm.nih.gov/pubmed/18059015", "http://www.ncbi.nlm.nih.gov/pubmed/25808752", "http://www.ncbi.nlm.nih.gov/pubmed/10631175", "http://www.ncbi.nlm.nih.gov/pubmed/9486541", "http://www.ncbi.nlm.nih.gov/pubmed/22507129", "http://www.ncbi.nlm.nih.gov/pubmed/11714677", "http://www.ncbi.nlm.nih.gov/pubmed/23928032", "http://www.ncbi.nlm.nih.gov/pubmed/10742444", "http://www.ncbi.nlm.nih.gov/pubmed/21411723", "http://www.ncbi.nlm.nih.gov/pubmed/10208865", "http://www.ncbi.nlm.nih.gov/pubmed/15355563", "http://www.ncbi.nlm.nih.gov/pubmed/11748145", "http://www.ncbi.nlm.nih.gov/pubmed/10465785", "http://www.ncbi.nlm.nih.gov/pubmed/11466306", "http://www.ncbi.nlm.nih.gov/pubmed/22190639", "http://www.ncbi.nlm.nih.gov/pubmed/14991716", "http://www.ncbi.nlm.nih.gov/pubmed/21566205", "http://www.ncbi.nlm.nih.gov/pubmed/10491221", "http://www.ncbi.nlm.nih.gov/pubmed/25479004", "http://www.ncbi.nlm.nih.gov/pubmed/19035497", "http://www.ncbi.nlm.nih.gov/pubmed/8662546", "http://www.ncbi.nlm.nih.gov/pubmed/24844414", "http://www.ncbi.nlm.nih.gov/pubmed/12968668" ], "ideal_answer": [ "Indian hedgehog is a protein that regulates endochondral differentiation and ossification in both a parathyroid hormone-related protein (PTHrP)-dependent and -independent manner by activating transcriptional mediator Gli2 and is an essential factor for proper skeletal development." ], "concepts": [ "http://www.uniprot.org/uniprot/IHH_DANAT", "http://www.uniprot.org/uniprot/IHH_RASEL", "http://www.uniprot.org/uniprot/IHH_CARAU", "http://www.uniprot.org/uniprot/IHH_CHICK", "http://www.uniprot.org/uniprot/IHH_DANAP", "http://www.uniprot.org/uniprot/IHH_TRIHE", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019902", "http://www.uniprot.org/uniprot/IHH_DEVDE", "http://www.uniprot.org/uniprot/IHH_RASPA", "http://www.uniprot.org/uniprot/IHH_MOUSE", "http://www.uniprot.org/uniprot/IHH_XENLA", "http://www.uniprot.org/uniprot/IHH_DEVPA", "http://www.uniprot.org/uniprot/IHH_DANKE", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019485", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053823", "http://www.uniprot.org/uniprot/IHH_HUMAN", "http://www.uniprot.org/uniprot/IHH_PUNTE", "http://www.uniprot.org/uniprot/IHH_DEVMA" ], "type": "summary", "id": "58b95ea222d3005309000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Indian hedgehog (Ihh) regulates endochondral ossification in both a parathyroid hormone-related protein (PTHrP)-dependent and -independent manner by activating transcriptional mediator Gli2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25808752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Wnt/\u03b2-catenin, Indian hedgehog (Ihh)/Parathyroid-related peptide (PTHrP) and retinoid signaling pathways regulate cartilage differentiation, growth, and function during development and play a key role in endochondral ossification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 434, "text": "Indian hedgehog (Ihh) is essential for chondrocyte differentiation and endochondral ossification and acts with parathyroid hormone-related peptide in a negative feedback loop to regulate early chondrocyte differentiation and entry to hypertrophic differentiation. Independent of this function, we and others recently reported independent Ihh functions to promote chondrocyte hypertrophy and matrix mineralization in vivo and in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25028519", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 708, "text": "We recently discovered that Ihh overexpression in chondrocytes stimulated the expression of late chondrocyte differentiation markers and induced matrix mineralization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25028519", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1155, "text": "In addition, we found that Ihh induced Runx2 expression in chondrocytes without up-regulating other modulators of chondrocyte maturation such as Mef2c, Foxa2, and Foxa3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25028519", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1756, "text": "Thus, Ihh signaling could be an important player for not only early chondrocyte differentiation but maturation and calcification of chondrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25028519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The Ihh signal is essential for regulating proliferation and hypertrophy of cultured chicken chondrocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928032", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The Indian hedgehog (Ihh) signal plays a vital role in regulating proliferation and hypertrophy of chondrocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928032", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1246, "text": "Based on these results, the Ihh signal is essential for balancing chicken chondrocyte proliferation and hypertrophy, and the regulatory function of PTHrP acts in an Ihh-dependent manner. Furthermore, BMP-6 and Bcl-2 played roles in maintaining the development of chondrocytes and may be downstream regulatory factors of Ihh signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Atf4 is a leucine zipper-containing transcription factor that activates osteocalcin (Ocn) in osteoblasts and indian hedgehog (Ihh) in chondrocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190639", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 327, "text": "Indian hedgehog (Ihh) is produced by prehypertrophic chondrocytes in developing long bones and regulates chondrocyte proliferation and other events, but it is not known whether it requires HS-PGs for function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14991716", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 459, "text": "We have shown that Indian hedgehog gene (Ihh) is expressed in cartilage anlage and later in mature and hypertrophic chondrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10615989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8662546", "endSection": "title" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1049, "text": "In normal growth plates, differentiation of proliferative chondrocytes to post-mitotic hypertrophic chondrocytes is regulated in part by a tightly coupled signaling relay involving parathyroid hormone related protein (PTHrP) and Indian hedgehog (IHH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The Indian hedgehog (Ihh) signal plays a vital role in regulating proliferation and hypertrophy of chondrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Indian hedgehog and syndecans-3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14991716", "endSection": "title" }, { "offsetInBeginSection": 714, "offsetInEndSection": 902, "text": "We further demonstrate that misexpression of Indian hedgehog appears to directly upregulate BMP2 and BMP4 expression, independent of the differentiation state of the flanking chondrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10328918", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 328, "text": "Indian hedgehog (Ihh) is produced by prehypertrophic chondrocytes in developing long bones and regulates chondrocyte proliferation and other events, but it is not known whether it requires HS-PGs for function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14991716", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1409, "text": "The cellular expression of two markers of chondrocyte differentiation, Indian hedgehog, expressed in pre-hypertrophic cells and collagen type X, expressed in hypertrophic chondrocytes, were both significantly inhibited after incubation with isoproterenol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18059015", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 327, "text": "Indian hedgehog (Ihh) is produced by prehypertrophic chondrocytes in developing long bones and regulates chondrocyte proliferation and other events, but it is not known whether it requires HS-PGs for function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14991716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Four distinct chondrocyte populations in the fetal bovine growth plate: highest expression levels of PTH/PTHrP receptor, Indian hedgehog, and MMP-13 in hypertrophic chondrocytes and their suppression by PTH (1-34) and PTHrP (1-40)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12213208", "endSection": "title" }, { "offsetInBeginSection": 129, "offsetInEndSection": 365, "text": "Although it is known that parathyroid hormone related protein (PTHrP) and Indian hedgehog regulate the differentiation of growth plate chondrocytes, how these pathways interact to regulate chondrocyte development is not fully elucidated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17328886", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 411, "text": "Indian hedgehog (Ihh) signaling from prehypertrophic chondrocytes has been implicated in the control of chondrocyte maturation by way of feedback control of a second secreted factor parathyroid hormone-related peptide (PTHrP) at the articular surfaces", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10465785", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Mutant BMP receptors were transfected into cultured embryonic upper sternal chrondrocytes using retroviral vectors to determine if BMP signaling is required for chondrocyte maturation and the expression of a key regulatory molecule, Indian hedgehog (Ihh)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11332615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Chondrocytes of the epiphyseal growth zone are regulated by the Indian hedgehog (IHH)-parathyroid hormone-related protein (PTHrP) axis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19035497", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1008, "text": "The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21566205", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1116, "text": "In an effort to lessen the severity of bone defects caused by HhAntag, we treated young mice simultaneously with HhAntag and parathyroid hormone-related protein (PTHrP), which functions downstream of Indian Hedgehog to maintain chondrocytes in a proliferative state. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21411723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Chondrocyte differentiation during embryonic bone growth is controlled by interactions between PTHrP and Indian hedgehog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11517192", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 329, "text": "Hedgehog genes encode secreted proteins which mediate patterning and growth during skeletal development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10615989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Indian hedgehog (Ihh) has recently been shown to be expressed in prehypertrophic and hypertrophic chondrocytes during embryonic development, and it has been implicated in the regulation of terminal differentiation of chondrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10742444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Indian hedgehog and syndecans-3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14991716", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Indian Hedgehog signalling triggers Nkx3.2 protein degradation during chondrocyte maturation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22507129", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Regulation of articular chondrocyte proliferation and differentiation by indian hedgehog and parathyroid hormone-related protein in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19035497", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Chondrocytes of the epiphyseal growth zone are regulated by the Indian hedgehog (IHH)-parathyroid hormone-related protein (PTHrP) axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19035497", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 746, "text": "Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9486541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Expression of indian hedgehog, bone morphogenetic protein 6 and gli during skeletal morphogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9486541", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18434416", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Age-dependent effects of hedgehog protein on chondrocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10615989", "endSection": "title" }, { "offsetInBeginSection": 367, "offsetInEndSection": 568, "text": "Indian hedgehog (Ihh), a secreted protein expressed in early hypertrophic chondrocytes, is thought to be involved in regulation of hypertrophic conversion via a feedback loop through the perichondrium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10208865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8662546", "endSection": "title" }, { "offsetInBeginSection": 1949, "offsetInEndSection": 2127, "text": "These observations are in keeping with the proposed function of gli as a negative regulator of Ihh signaling and the induction of Bmps by Hedgehog proteins (Roberts et al., 1995.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9486541", "endSection": "abstract" } ] }, { "body": "What is the function of R-spondin 1 and noggin in non-damaged gallbladders?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26993089" ], "ideal_answer": [ "R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders." ], "exact_answer": [ "The expansion of resident stem cells." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005704", "http://www.biosemantics.org/jochem#4264633", "http://www.uniprot.org/uniprot/NOGG_HUMAN", "http://www.uniprot.org/uniprot/RSPO1_MOUSE", "http://www.uniprot.org/uniprot/RSPO1_DANRE", "http://www.uniprot.org/uniprot/SPON1_MOUSE", "http://www.uniprot.org/uniprot/RSPO1_HUMAN", "http://www.uniprot.org/uniprot/SPON1_RAT", "http://www.uniprot.org/uniprot/SPON1_CHICK", "http://www.uniprot.org/uniprot/NOGG_XENLA", "http://www.uniprot.org/uniprot/SPON1_XENLA" ], "type": "factoid", "id": "5883a727e56acf5176000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26993089", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26993089", "endSection": "title" } ] }, { "body": "List the classical triad of symptoms of the Melkersson\u2013Rosenthal syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16856704", "http://www.ncbi.nlm.nih.gov/pubmed/1597367", "http://www.ncbi.nlm.nih.gov/pubmed/15865255", "http://www.ncbi.nlm.nih.gov/pubmed/16989500", "http://www.ncbi.nlm.nih.gov/pubmed/10481507", "http://www.ncbi.nlm.nih.gov/pubmed/11995671", "http://www.ncbi.nlm.nih.gov/pubmed/24874612", "http://www.ncbi.nlm.nih.gov/pubmed/10938204", "http://www.ncbi.nlm.nih.gov/pubmed/10534638", "http://www.ncbi.nlm.nih.gov/pubmed/14980194", "http://www.ncbi.nlm.nih.gov/pubmed/10332378", "http://www.ncbi.nlm.nih.gov/pubmed/12783021", "http://www.ncbi.nlm.nih.gov/pubmed/1923442", "http://www.ncbi.nlm.nih.gov/pubmed/24827666", "http://www.ncbi.nlm.nih.gov/pubmed/15068454", "http://www.ncbi.nlm.nih.gov/pubmed/2584463", "http://www.ncbi.nlm.nih.gov/pubmed/7856459", "http://www.ncbi.nlm.nih.gov/pubmed/8725591", "http://www.ncbi.nlm.nih.gov/pubmed/24656464", "http://www.ncbi.nlm.nih.gov/pubmed/24225172", "http://www.ncbi.nlm.nih.gov/pubmed/22836908", "http://www.ncbi.nlm.nih.gov/pubmed/7640193", "http://www.ncbi.nlm.nih.gov/pubmed/3228056", "http://www.ncbi.nlm.nih.gov/pubmed/26635986", "http://www.ncbi.nlm.nih.gov/pubmed/8302226", "http://www.ncbi.nlm.nih.gov/pubmed/12081001", "http://www.ncbi.nlm.nih.gov/pubmed/16096940", "http://www.ncbi.nlm.nih.gov/pubmed/9224474", "http://www.ncbi.nlm.nih.gov/pubmed/17103360", "http://www.ncbi.nlm.nih.gov/pubmed/26698837" ], "ideal_answer": [ "The Melkersson-Rosenthal syndrome consists of the classical triad of symptoms:\n1) orofacial oedema \n2) fissured tongue (lingua plicata) and\n3) facial paralysis." ], "exact_answer": [ [ "orofacial oedema", "lip and face swelling" ], [ "fissured tongue", "lingua plicata" ], [ "facial paralysis", "facial palsy" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:1761", "http://www.disease-ontology.org/api/metadata/DOID:225", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008556" ], "type": "list", "id": "58b53bf722d3005309000004", "snippets": [ { "offsetInBeginSection": 310, "offsetInEndSection": 451, "text": "The Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "endSection": "abstract" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1150, "text": "The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 182, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24656464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare granulomatous inflammatory disease characterised by the triad of orofacial oedema, facial nerve palsy and furrowed tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24827666", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 221, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous granulomatous disorder of unknown etiology, characterized by the triad of facial palsy, lingua plicata (fissured tongue), and orofacial edema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24874612", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 352, "text": "Melkerrson-Rosenthal syndrome is a rare disorder of unknown etiology. The classical triad of recurrent facial paralysis, swelling of the face, lips and deep furrowed tongue (Lingua Plicata) is seen in very few cases, majority of the patients often present with one or two symptoms only, which often leads to misdiagnosis and mismanagement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare neuromucocutaneous syndrome marked by the triad of recurrent nonpitting orofacial edema, fissured dorsal tongue (lingua plicata), and lower motoneuron facial paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22836908", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 510, "text": "Recurrent facial nerve palsy, facial swelling, and fissured tongue are the symptoms and signs of this condition. However, this triad is not typical in all patients as patients may present with one or more of the symptoms, which makes management of this condition difficult. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26635986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14980194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Melkersson-Rosenthal Syndrome (MRS) is a systemic neuro-mucocutaneous granulomatous disease, characterized in its classical form by a triad of recurrent facial nerve paralysis, swelling of the lips and lingua plicata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16856704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Melkersson-Rosenthal syndrome is classically described as a triad of orofacial swelling, facial palsy, and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10332378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Melkersson-Rosenthal syndrome is a rare disorder consisting of the triad of persistent or recurrent orofacial edema, relapsing facial paralysis and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10938204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10534638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The Melkersson-Rosenthal syndrome consists of a triad of symptoms: peripheral facial nerve paralysis, congenital \"lingua plicata\" and noninflammatory facial oedema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10481507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The Melkersson-Rosenthal syndrome consists of triad of symptoms: recurrent oedema of lips, recurrent facial nerve paralysis and lingua plicata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15865255", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 254, "text": "Melkersson-Rosenthal syndrome is characterised by a triad of recurrent orofacial swelling, relapsing facial paralysis, and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The Melkersson-Rosenthal syndrome consists of triad of symptoms: recurrent oedema of lips, recurrent facial nerve paralysis and lingua plicata", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15865255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14980194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown etiology characterized by a triad of symptoms: recurrent orofacial swelling, relapsing facial palsy. and a fissured tongue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11995671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The Melkersson-Rosenthal syndrome consists of a triad of symptoms: peripheral facial nerve paralysis, congenital \"lingua plicata\" and noninflammatory facial oedema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10481507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1597367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Peripheral facial nerve palsy, recurrent or persistent oral or facial swelling, and fissured tongue constitute a triad of symptoms known as Melkersson-Rosenthal syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1923442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Melkersson-Rosenthal (MRS) syndrome is characterized by a classical triad of recurrent or persistent orofacial swelling, peripheral facial nerve paralysis and lingua plicata. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15068454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "BACKGROUND: Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14980194", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 312, "text": "The syndrome is classically characterized by a triad of signs consisting of facial edema, recurrent peripheral facial nerve paralysis, and congenital fissured tongue, although it may also present in a mono- or oligosymptomatic form. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16096940", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 209, "text": "The classic triad of signs includes recurrent orofacial edema, recurrent facial nerve palsy, and lingua plicata. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2584463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1597367", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1113, "text": "The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Peripheral facial nerve palsy, recurrent or persistent oral or facial swelling, and fissured tongue constitute a triad of symptoms known as Melkersson-Rosenthal syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1923442", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 160, "text": "Classical signs include recurrent facial palsy, lingua plicata and orofacial edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8302226", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 236, "text": "The classical triad includes recurrent orofacial oedema involving predominantly the lips (macrocheilitis), intermittent peripheral facial palsy and scrotal tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7856459", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1114, "text": "The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "endSection": "abstract" } ] }, { "body": "Which disease is treated with taliglucerase alfa?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27102949", "http://www.ncbi.nlm.nih.gov/pubmed/23980545", "http://www.ncbi.nlm.nih.gov/pubmed/27174694", "http://www.ncbi.nlm.nih.gov/pubmed/21235447", "http://www.ncbi.nlm.nih.gov/pubmed/24630271", "http://www.ncbi.nlm.nih.gov/pubmed/27559188", "http://www.ncbi.nlm.nih.gov/pubmed/21900191", "http://www.ncbi.nlm.nih.gov/pubmed/27499018", "http://www.ncbi.nlm.nih.gov/pubmed/26053270", "http://www.ncbi.nlm.nih.gov/pubmed/22654679", "http://www.ncbi.nlm.nih.gov/pubmed/23199589", "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "http://www.ncbi.nlm.nih.gov/pubmed/25453586", "http://www.ncbi.nlm.nih.gov/pubmed/23046562", "http://www.ncbi.nlm.nih.gov/pubmed/27839981", "http://www.ncbi.nlm.nih.gov/pubmed/25812601", "http://www.ncbi.nlm.nih.gov/pubmed/22916340" ], "ideal_answer": [ "Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease." ], "exact_answer": [ "Gaucher disease" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category" ], "type": "factoid", "id": "5891b125621ea6ff7e00000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27102949", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Taliglucerase alfa is the first available plant cell-expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27102949", "endSection": "abstract" }, { "offsetInBeginSection": 1425, "offsetInEndSection": 1656, "text": "The 36-month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27102949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Long-term efficacy and safety results of taliglucerase alfa up to 36 months in adult treatment-na\u00efve patients with Gaucher disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27174694", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Taliglucerase alfa is an intravenous enzyme replacement therapy approved for treatment of type 1 Gaucher disease (GD), and is the first available plant cell-expressed recombinant therapeutic protein. Herein, we report long-term safety and efficacy results of taliglucerase alfa in treatment-na\u00efve adult patients with GD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27174694", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1168, "text": " These 36-month results of taliglucerase alfa in treatment-na\u00efve adult patients with GD demonstrate continued improvement in disease parameters with no new safety concerns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27174694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-na\u00efve patients with Gaucher disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27499018", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27499018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-na\u00efve or previously treated with imiglucerase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27839981", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "title" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1496, "text": "These results support safety and efficacy of taliglucerase alfa for Gaucher disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23199589", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Taliglucerase alfa for the treatment of Gaucher's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22916340", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Safety and efficacy of two dose levels of taliglucerase alfa in pediatric patients with Gaucher disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25453586", "endSection": "title" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1506, "text": "These results support safety and efficacy of taliglucerase alfa for Gaucher disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21900191", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1372, "text": "These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 543, "text": "This multicenter, randomized, double-blind, parallel-dose, 12-month study assessed efficacy and safety of taliglucerase alfa in pediatric patients with GD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25453586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "title" }, { "offsetInBeginSection": 308, "offsetInEndSection": 520, "text": "A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1371, "text": "These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1396, "text": "Clinical trials have demonstrated that taliglucerase alfa is efficacious, with a well-established safety profile in adult, ERT-na\u00efve patients with symptomatic GD1, and for such patients previously treated with imiglucerase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630271", "endSection": "abstract" }, { "offsetInBeginSection": 2407, "offsetInEndSection": 3070, "text": "One study examined substrate reduction therapy in people with chronic neuronopathic (type 3) Gaucher disease who continued to receive enzyme replacement therapy.Treatment-na\u00efve participants had similar increases in haemoglobin when comparing those receiving imiglucerase or alglucerase at 60 units/kg, imiglucerase or velaglucerase alfa at 60 U/kg, taliglucerase alfa at 30 units/kg or 60 units/kg, and velaglucerase alfa at 45 units/g or 60 units/kg. For platelet count response in participants with intact spleens, a benefit for imiglucerase over velaglucerase alfa at 60 units/kg was observed, mean difference -79.87 (95% confidence interval -137.57 to -22.17)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25812601", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1373, "text": "These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Taliglucerase alfa (Protalix Biotherapeutics, Israel) is a carrot-cell-expressed recombinant human beta-glucocerebrosidase recently approved in the United States for the treatment of type 1 Gaucher disease (GD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23199589", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1168, "text": "These 36-month results of taliglucerase alfa in treatment-na\u00efve adult patients with GD demonstrate continued improvement in disease parameters with no new safety concerns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27174694", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 521, "text": "A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1397, "text": "Clinical trials have demonstrated that taliglucerase alfa is efficacious, with a well-established safety profile in adult, ERT-na\u00efve patients with symptomatic GD1, and for such patients previously treated with imiglucerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24630271", "endSection": "abstract" }, { "offsetInBeginSection": 1509, "offsetInEndSection": 1628, "text": "These data suggest that taliglucerase alfa has the potential to be a therapeutic treatment option for children with GD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25453586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27102949", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-na\u00efve or previously treated with imiglucerase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27839981", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950666", "endSection": "title" } ] }, { "body": "What is formin associated with in the snail?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26923788" ], "ideal_answer": [ "Formin is associated with Left-Right asymmetry in the pond snail and the frog.", "Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog" ], "exact_answer": [ "Left-Right Asymmetry" ], "concepts": [ "http://www.uniprot.org/uniprot/FMNL1_HUMAN", "http://www.biosemantics.org/jochem#4263720", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052078", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012908" ], "type": "factoid", "id": "587f795d92a5b8ad44000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26923788", "endSection": "title" }, { "offsetInBeginSection": 467, "offsetInEndSection": 1355, "text": " Here, we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models [3, 4 and 5], we discovered asymmetric gene expression in 2- and 4-cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro [6 and 7], together these results are consistent with the view that animals with diverse body plans may derive their asymmetries from the same intracellular chiral elements [8].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26923788", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 636, "text": "Here, we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry breaking in the pond snail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26923788", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 906, "text": "This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26923788", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 639, "text": "Here, we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry breaking in the pond snail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26923788", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 909, "text": "This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26923788", "endSection": "abstract" } ] }, { "body": "What is the major difference between eucaryotes and procaryotes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16775624", "http://www.ncbi.nlm.nih.gov/pubmed/3271526", "http://www.ncbi.nlm.nih.gov/pubmed/7533711", "http://www.ncbi.nlm.nih.gov/pubmed/98518", "http://www.ncbi.nlm.nih.gov/pubmed/3023854", "http://www.ncbi.nlm.nih.gov/pubmed/2345155", "http://www.ncbi.nlm.nih.gov/pubmed/7786016" ], "ideal_answer": [ "Eucaryotes have a nucleolus, Procaryotes do not. Eucrayotes have a nuclear membrane, organelles and differ in transcription and translation. Procaryotes have polycistronic RNA and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes. ", "The nucleolus is the most prominent compartment in the nucleus and known as the site for ribosome biogenesis in eucaryotes. In contrast, there is no such equivalent structure for ribosome synthesis in procaryotes Eucaryotic and procaryotic organisms differ in two aspects of their translation machinery: polycistronic messengers are expressed as a sequence of individual proteins only in procaryotes, and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes.", "The nucleolus is the most prominent compartment in the nucleus and known as the site for ribosome biogenesis in eucaryotes. In contrast, there is no such equivalent structure for ribosome synthesis in procaryotes Eucaryotic and procaryotic organisms differ in two aspects of their translation machinery: polycistronic messengers are expressed as a sequence of individual proteins only in procaryotes, and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes. extra guanylate at the 5' end of mature E. coli tRNAHis is encoded in the gene and is found in tRNA as the result of an unusual cleavage by RNase P There are considerable differences of run distributions in DNA sequences of procaryotes, invertebrates and vertebrates. However, some interesting exceptions from this rule exist for the run distribution of adenine in procaryotes and for the arrangement of purine-pyrimidine runs in eucaryotes" ], "type": "summary", "id": "58a1c6b678275d0c4a000057", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The nucleolus is the most prominent compartment in the nucleus and known as the site for ribosome biogenesis in eucaryotes. In contrast, there is no such equivalent structure for ribosome synthesis in procaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16775624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Eucaryotic and procaryotic organisms differ in two aspects of their translation machinery: polycistronic messengers are expressed as a sequence of individual proteins only in procaryotes, and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/98518", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 503, "text": "extra guanylate at the 5' end of mature E. coli tRNAHis is encoded in the gene and is found in tRNA as the result of an unusual cleavage by RNase P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3023854", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 250, "text": " There are considerable differences of run distributions in DNA sequences of procaryotes, invertebrates and vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3271526", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 571, "text": "However, some interesting exceptions from this rule exist for the run distribution of adenine in procaryotes and for the arrangement of purine-pyrimidine runs in eucaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3271526", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1447, "text": "This was thought to be explained by the lack of mitochondria in procaryotes, the target site of uncoupling agents in eucaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7533711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Eucaryotic and procaryotic organisms differ in two aspects of their translation machinery: polycistronic messengers are expressed as a sequence of individual proteins only in procaryotes, and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/98518", "endSection": "abstract" } ] }, { "body": "What is the HSP70-HSP110 disaggregase machinery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27477512" ], "ideal_answer": [ "Clearance of misfolded and aggregated proteins is central to cell survival. UBQLN2 acts with the HSP70-HSP110 disaggregase machinery to clear protein aggregates via the 26S proteasome. UBQLN2 recognizes client-bound HSP70 and links it to the proteasome to allow for the degradation of aggregated and misfolded proteins. We further show that this process is active in the cell nucleus, where another system for aggregate clearance, autophagy, does not act." ], "type": "summary", "id": "58bc640002b8c60953000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Clearance of misfolded and aggregated proteins is central to cell survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27477512", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 851, "text": "UBQLN2 acts with the HSP70-HSP110 disaggregase machinery to clear protein aggregates via the 26S proteasome. UBQLN2 recognizes client-bound HSP70 and links it to the proteasome to allow for the degradation of aggregated and misfolded proteins. We further show that this process is active in the cell nucleus, where another system for aggregate clearance, autophagy, does not act. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27477512", "endSection": "abstract" } ] }, { "body": "Has whole exome sequencing been performed in Alzheimer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22153900", "http://www.ncbi.nlm.nih.gov/pubmed/23237904", "http://www.ncbi.nlm.nih.gov/pubmed/24958194", "http://www.ncbi.nlm.nih.gov/pubmed/27822510", "http://www.ncbi.nlm.nih.gov/pubmed/22472873", "http://www.ncbi.nlm.nih.gov/pubmed/26522186" ], "ideal_answer": [ "Yes, numerous whole exome sequencing studies of ALzheimer patients have been conducted." ], "exact_answer": "yes", "type": "yesno", "id": "58bbb8ae22d3005309000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26522186", "endSection": "title" }, { "offsetInBeginSection": 129, "offsetInEndSection": 304, "text": "We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822510", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 480, "text": "Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24958194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23237904", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 493, "text": "We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22153900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22472873", "endSection": "abstract" } ] }, { "body": "Which is the genome browser database for DNA shape annotations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25326329" ], "ideal_answer": [ "GBshape provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution." ], "exact_answer": [ "GBshape" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ], "type": "factoid", "id": "587e1bfdfc7e8dd84f000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "GBshape: a genome browser database for DNA shape annotations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 1352, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "GBshape: a genome browser database for DNA shape annotations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "title" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1072, "text": "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 785, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1078, "text": "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1077, "text": "GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "GBshape: a genome browser database for DNA shape annotations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 788, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract" } ] }, { "body": "Is Stat4 a transcription factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25178516", "http://www.ncbi.nlm.nih.gov/pubmed/25829541", "http://www.ncbi.nlm.nih.gov/pubmed/25798064", "http://www.ncbi.nlm.nih.gov/pubmed/25852285" ], "ideal_answer": [ "Yes, Stat4 is a transcription factor.\nStat4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus." ], "exact_answer": "yes", "type": "yesno", "id": "58bc58c302b8c60953000001", "snippets": [ { "offsetInBeginSection": 713, "offsetInEndSection": 750, "text": "transcription factors T-bet and STAT4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25829541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "STAT4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25798064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "STAT4 is a latent cytosolic factor that encodes a transcription factor transmitting signals stimulated by cytokines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25178516", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 168, "text": " To investigate the role of signal transduction and activation of transcription 4 (STAT4) in the development and progression of human hepatocellular carcinoma (HCC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25852285", "endSection": "abstract" } ] }, { "body": "Have the promoter regions of the genes implicated in Rett Syndrome been characterized with CAGE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25539566" ], "ideal_answer": [ "Yes. Promoter regions of the genes implicated in Rett Syndrome have been characterized using CAGE." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015518", "http://www.disease-ontology.org/api/metadata/DOID:1206", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011401" ], "type": "yesno", "id": "589644c478275d0c4a00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "CAGE-defined promoter regions of the genes implicated in Rett Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25539566", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1212, "text": "Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.RESULTS: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25539566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "CAGE-defined promoter regions of the genes implicated in Rett Syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25539566", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "CAGE-defined promoter regions of the genes implicated in Rett Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25539566", "endSection": "title" } ] }, { "body": "Has \"RNA interference\" been awarded Nobel prize?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20717561", "http://www.ncbi.nlm.nih.gov/pubmed/24235106", "http://www.ncbi.nlm.nih.gov/pubmed/26648823", "http://www.ncbi.nlm.nih.gov/pubmed/25048083" ], "ideal_answer": [ "Since the first unequivocal description of RNA interference (RNAi) in 1998, it has remained one of the hottest topics under investigation, culminating in the award of a Nobel Prize to its discoverers in 2006." ], "exact_answer": "yes", "type": "yesno", "id": "58bbb68b22d3005309000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Since the first unequivocal description of RNA interference (RNAi) in 1998, it has remained one of the hottest topics under investigation, culminating in the award of a Nobel Prize to its discoverers in 2006.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20717561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "RNA interference (RNAi) is considered one of the most powerful genomic tools which allows the study of drug discovery and understanding of the complex cellular processes by high-content screens. This field of study, which was the subject of 2006 Nobel Prize of medicine, has drastically changed the conventional methods of analysis of genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24235106", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 373, "text": " Almost 10 years after Fire and Mello received the Nobel Prize for the discovery of this mechanism in flat worms, RNA interference is on the edge of becoming a new class of therapeutics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26648823", "endSection": "abstract" } ] }, { "body": "Is there any role for Pds5b in cohesion establishment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24141881" ], "ideal_answer": [ "Yes. Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/PD5AA_XENLA", "http://www.uniprot.org/uniprot/PD5BA_XENLA", "http://www.uniprot.org/uniprot/PDS5A_RAT", "http://amigo.geneontology.org/amigo/term/GO:0034085", "http://www.uniprot.org/uniprot/PDS5B_RAT", "http://amigo.geneontology.org/amigo/term/GO:0034087", "http://www.uniprot.org/uniprot/PDS5B_MOUSE", "http://amigo.geneontology.org/amigo/term/GO:0034089" ], "type": "yesno", "id": "5889e2c83b87a8a73800000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141881", "endSection": "title" }, { "offsetInBeginSection": 444, "offsetInEndSection": 1070, "text": "Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin. While both proteins contribute to telomere and arm cohesion, Pds5B is specifically required for centromeric cohesion. Furthermore, reduced accumulation of Aurora B at the inner centromere region in cells lacking Pds5B impairs its error correction function, promoting chromosome mis-segregation and aneuploidy. Our work supports a model in which the composition and function of cohesin complexes differs between different chromosomal regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141881", "endSection": "title" }, { "offsetInBeginSection": 444, "offsetInEndSection": 628, "text": "Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141881", "endSection": "abstract" } ] }, { "body": "Which factors are considered in the FUNC score for intracerebral hemorrhage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18556582" ], "ideal_answer": [ "FUNC score includes Age, Glasgow Coma Scale, ICH location, volume and pre-ICH cognitive impairment." ], "exact_answer": [ [ "Age" ], [ "Glasgow Coma Scale" ], [ "ICH location" ], [ "ICH volume" ], [ "pre-ICH cognitive impairment" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020299" ], "type": "list", "id": "58850e50e56acf5176000013", "snippets": [ { "offsetInBeginSection": 782, "offsetInEndSection": 1065, "text": "Age, Glasgow Coma Scale, ICH location, volume (all P<0.0001), and pre-ICH cognitive impairment (P=0.005) were independently associated with Glasgow Outcome Score>or = 4. The FUNC score was developed as a sum of individual points (0-11) based on strength of association with outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18556582", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 951, "text": "Age, Glasgow Coma Scale, ICH location, volume (all P<0.0001), and pre-ICH cognitive impairment (P=0.005) were independently associated with Glasgow Outcome Score>or = 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18556582", "endSection": "abstract" } ] }, { "body": "Where is the respirasome located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27830641", "http://www.ncbi.nlm.nih.gov/pubmed/27912054" ], "ideal_answer": [ "Respirasomes are macromolecular assemblies of the respiratory chain complexes I, III and IV in the inner mitochondrial membrane. The 4.0 \u00c5 cryo-EM structure of one of the most intricate enzyme systems, the respirasome, in the mitochondrial inner membrane is now available." ], "exact_answer": [ "In the inner mitochondrial membrane" ], "type": "factoid", "id": "58a9d8a1396a458e50000005", "snippets": [ { "offsetInBeginSection": 181, "offsetInEndSection": 305, "text": "he 4.0\u00a0\u00c5 cryo-EM structure of one of the most intricate enzyme systems, the respirasome, in the mitochondrial inner membrane", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27912054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Respirasomes are macromolecular assemblies of the respiratory chain complexes I, III and IV in the inner mitochondrial membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27830641", "endSection": "abstract" } ] }, { "body": "Describe the usefulness of MiRduplexSVM.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25961860" ], "ideal_answer": [ "MiRduplexSVM is a high-performing miRNA-duplex prediction and evaluation methodology. It's a method that combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model. It is the first model that provides precise information about all four ends of the miRNA duplex." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "summary", "id": "5895ee638707e6ea39000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "MiRduplexSVM: A High-Performing MiRNA-Duplex Prediction and Evaluation Methodology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "title" }, { "offsetInBeginSection": 160, "offsetInEndSection": 426, "text": "Our method combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model, termed MiRduplexSVM. This is the first model that provides precise information about all four ends of the miRNA duplex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "abstract" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1565, "text": "In relation with recent confidence evaluation methods used in miRBase, MiRduplexSVM was successful in identifying high confidence potential miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 325, "text": "Our method combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model, termed MiRduplexSVM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 908, "text": "(b) In all comparisons, MiRduplexSVM shows superior performance, achieving up to a 60% increase in prediction accuracy for mammalian hairpins and can generalize very well on plant hairpins, without any special optimization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "MiRduplexSVM: A High-Performing MiRNA-Duplex Prediction and Evaluation Methodology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "title" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1573, "text": "In relation with recent confidence evaluation methods used in miRBase, MiRduplexSVM was successful in identifying high confidence potential miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 326, "text": "Our method combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model, termed MiRduplexSVM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 912, "text": "(b) In all comparisons, MiRduplexSVM shows superior performance, achieving up to a 60% increase in prediction accuracy for mammalian hairpins and can generalize very well on plant hairpins, without any special optimization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961860", "endSection": "abstract" } ] }, { "body": "What genes are drug targets for Fibrodysplasia Ossificans Progressiva (FOP)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15940369", "http://www.ncbi.nlm.nih.gov/pubmed/22011642", "http://www.ncbi.nlm.nih.gov/pubmed/25136070", "http://www.ncbi.nlm.nih.gov/pubmed/17967130", "http://www.ncbi.nlm.nih.gov/pubmed/23646137", "http://www.ncbi.nlm.nih.gov/pubmed/26695699", "http://www.ncbi.nlm.nih.gov/pubmed/24047559", "http://www.ncbi.nlm.nih.gov/pubmed/11076054", "http://www.ncbi.nlm.nih.gov/pubmed/23599718", "http://www.ncbi.nlm.nih.gov/pubmed/15288357", "http://www.ncbi.nlm.nih.gov/pubmed/23229308", "http://www.ncbi.nlm.nih.gov/pubmed/19795179", "http://www.ncbi.nlm.nih.gov/pubmed/26621707", "http://www.ncbi.nlm.nih.gov/pubmed/19400542", "http://www.ncbi.nlm.nih.gov/pubmed/16080294", "http://www.ncbi.nlm.nih.gov/pubmed/25413979", "http://www.ncbi.nlm.nih.gov/pubmed/16753021", "http://www.ncbi.nlm.nih.gov/pubmed/18830232", "http://www.ncbi.nlm.nih.gov/pubmed/24705252", "http://www.ncbi.nlm.nih.gov/pubmed/17477807", "http://www.ncbi.nlm.nih.gov/pubmed/18328989", "http://www.ncbi.nlm.nih.gov/pubmed/19929436", "http://www.ncbi.nlm.nih.gov/pubmed/22408438", "http://www.ncbi.nlm.nih.gov/pubmed/26058333", "http://www.ncbi.nlm.nih.gov/pubmed/22977237", "http://www.ncbi.nlm.nih.gov/pubmed/26896819", "http://www.ncbi.nlm.nih.gov/pubmed/9042799", "http://www.ncbi.nlm.nih.gov/pubmed/26626181", "http://www.ncbi.nlm.nih.gov/pubmed/16831905", "http://www.ncbi.nlm.nih.gov/pubmed/26333933", "http://www.ncbi.nlm.nih.gov/pubmed/11140409", "http://www.ncbi.nlm.nih.gov/pubmed/22408652" ], "ideal_answer": [ " Recently, FOP has been associated with a specific mutation of ACVR1, the gene coding for a bone morphogenetic protein type I receptor. ", "here, it is noted that if b cells are found to be the lymphocytes responsible for excess bmp-4 production in fop, use of rituximab, a monoclonal anti-cd20 antibody which effectively targets b cells, could be a less permanent and less risky treatment alternative for fop.", "Inhibitors of ALK2(ACVR1) are used for the treatment of FOP. Current therapies for FOP are Dorsomorphin analogues which function as BMP inhibitor. if B cells control excess BMP-4 production in FOP, use of Rituximab, a monoclonal which targets B cells, could be a treatment alternative for FOP." ], "exact_answer": [ [ "ALK2" ], [ "BMP" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:13374", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055415", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052005" ], "type": "list", "id": "589dee3778275d0c4a000050", "snippets": [ { "offsetInBeginSection": 294, "offsetInEndSection": 430, "text": " Recently, FOP has been associated with a specific mutation of ACVR1, the gene coding for a bone morphogenetic protein type I receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18830232", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 371, "text": "Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23646137", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 484, "text": "Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23646137", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 733, "text": "By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23646137", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 1050, "text": "Here, it is noted that if B cells are found to be the lymphocytes responsible for excess BMP-4 production in FOP, use of Rituximab, a monoclonal anti-CD20 antibody which effectively targets B cells, could be a less permanent and less risky treatment alternative for FOP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15288357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "A new mutation of the Noggin gene in a French Fybrodysplasia ossificans progressiva (FOP) family: Fibrodysplasia ossificans progressiva (FOP) is a very rare disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of the muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16080294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Localization of the gene for fibrodysplasia ossificans progressiva (FOP) to chromosome 17q21-22.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11140409", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A new mutation of the noggin gene in a French Fibrodysplasia ossificans progressiva (FOP) family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16080294", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Rarely occurring mutation of ACVR1 gene in Moroccan patient with fibrodysplasia ossificans progressiva.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19795179", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "A new mutation of the Noggin gene in a French Fybrodysplasia ossificans progressiva (FOP) family: Fibrodysplasia ossificans progressiva (FOP) is a very rare disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of the muscles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16080294", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 368, "text": "Mutations in the ACVR1 gene are associated with Fibrodysplasia Ossificans Progressiva (FOP), a rare and extremely disabling disorder characterized by congenital malformation of the great toes and progressive heterotopic endochondral ossification in muscles and other non-skeletal tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24047559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Mutations of the noggin (NOG) and of the activin A type I receptor (ACVR1) genes in a series of twenty-seven French fibrodysplasia ossificans progressiva (FOP) patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19400542", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "ACVR1, a therapeutic target of fibrodysplasia ossificans progressiva, is negatively regulated by miR-148a.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22408438", "endSection": "title" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1140, "text": "These mutations represent new targets for therapeutic intervention in this otherwise incurable disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705252", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1041, "text": "In this study, we examined downstream signaling targets to study the BMP-Smad and BMP-p38 mitogen-activated protein kinase (MAPK) pathways in FOP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16753021", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 382, "text": "Mutations in the ACVR1 gene are associated with Fibrodysplasia Ossificans Progressiva (FOP), a rare and extremely disabling disorder characterized by congenital malformation of the great toes and progressive heterotopic endochondral ossification in muscles and other non-skeletal tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24047559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11076054", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 375, "text": "Fibrodysplasia ossificans progressiva (FOP), a rare disorder characterized by progressive ossification of connective tissue, is caused by an activating mutation in Acvr1 (the gene that encodes ACVR1/ALK2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25413979", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 488, "text": "This gene encodes the type I bone morphogenic protein receptor ALK2, with the residues affected identical to those that, when mutated in the germline, give rise to the congenital malformation syndrome fibrodysplasia ossificans progressiva (FOP), resulting in the transformation of soft tissue into bone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25136070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "ACVR1, a therapeutic target of fibrodysplasia ossificans progressiva, is negatively regulated by miR-148a.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22408438", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "A new mutation of the noggin gene in a French Fibrodysplasia ossificans progressiva (FOP) family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16080294", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Neofunction of ACVR1 in fibrodysplasia ossificans progressiva.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26621707", "endSection": "title" }, { "offsetInBeginSection": 276, "offsetInEndSection": 554, "text": "The discovery of the FOP gene establishes a crucial milestone in understanding FOP, reveals a highly conserved target in the BMP signaling pathway for drug development and specifically stimulates therapeutic approaches for the development of inhibitors for ACVR1/ALK2 signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23599718", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 1069, "text": "The discovery of the FOP gene establishes a critical milestone in understanding FOP, reveals a highly conserved druggable target in the TGF-beta/bone morphogenetic protein signaling pathway and compels therapeutic approaches for the development of small molecule signal transduction inhibitors for activin-like kinase-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17477807", "endSection": "abstract" } ] }, { "body": "What kind of analyses are performed with the software tool \"unipept\"", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26819472", "http://www.ncbi.nlm.nih.gov/pubmed/26058579", "http://www.ncbi.nlm.nih.gov/pubmed/27380722", "http://www.ncbi.nlm.nih.gov/pubmed/23153116", "http://www.ncbi.nlm.nih.gov/pubmed/25477242" ], "ideal_answer": [ "The Unipept web application (http://unipept.ugent.be) supports biodiversity analysis of large and complex metaproteome samples using tryptic peptide information obtained from shotgun MS/MS experiments. The application designed for metaproteomics analysis with a focus on interactive datavisualization." ], "type": "summary", "id": "58bbbf3722d300530900001b", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 146, "text": "Unipept is an open source web application that is designed for metaproteomics analysis with a focus on interactive datavisualization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26819472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The Unique Peptide Finder (http://unipept.ugent.be/peptidefinder) is an interactive web application to quickly hunt for tryptic peptides that are unique to a particular species, genus, or any other taxon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27380722", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1164, "text": "Computations are extremely fast since they are underpinned by the Unipept database, the lowest common ancestor algorithm implemented in Unipept and modern web technologies that facilitate in-browser data storage and parallel processing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27380722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Unipept (http://unipept.ugent.be) is a web application that offers a user-friendly way to explore the biodiversity of complex metaproteome samples by providing interactive visualizations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25477242", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1281, "text": "Outputted results are compatible with tools for taxonomic and functional characterization (e.g. Unipept, MEGAN5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26058579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The Unipept web application (http://unipept.ugent.be) supports biodiversity analysis of large and complex metaproteome samples using tryptic peptide information obtained from shotgun MS/MS experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23153116", "endSection": "abstract" } ] }, { "body": "What is the role of gamma-secreatase complex in Alzheimer's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18320103", "http://www.ncbi.nlm.nih.gov/pubmed/26559975", "http://www.ncbi.nlm.nih.gov/pubmed/24900409", "http://www.ncbi.nlm.nih.gov/pubmed/17298085", "http://www.ncbi.nlm.nih.gov/pubmed/15766275", "http://www.ncbi.nlm.nih.gov/pubmed/19299585", "http://www.ncbi.nlm.nih.gov/pubmed/19958468", "http://www.ncbi.nlm.nih.gov/pubmed/18063223", "http://www.ncbi.nlm.nih.gov/pubmed/23316412", "http://www.ncbi.nlm.nih.gov/pubmed/20035833", "http://www.ncbi.nlm.nih.gov/pubmed/18038124", "http://www.ncbi.nlm.nih.gov/pubmed/17560791", "http://www.ncbi.nlm.nih.gov/pubmed/16675392", "http://www.ncbi.nlm.nih.gov/pubmed/15992373", "http://www.ncbi.nlm.nih.gov/pubmed/19625750", "http://www.ncbi.nlm.nih.gov/pubmed/16804564", "http://www.ncbi.nlm.nih.gov/pubmed/23379308", "http://www.ncbi.nlm.nih.gov/pubmed/18393798", "http://www.ncbi.nlm.nih.gov/pubmed/20445084", "http://www.ncbi.nlm.nih.gov/pubmed/16944319", "http://www.ncbi.nlm.nih.gov/pubmed/19376115", "http://www.ncbi.nlm.nih.gov/pubmed/19181896", "http://www.ncbi.nlm.nih.gov/pubmed/21487536", "http://www.ncbi.nlm.nih.gov/pubmed/20129170", "http://www.ncbi.nlm.nih.gov/pubmed/20600609" ], "ideal_answer": [ "The gamma-secretase complex has a decisive role in the development of Alzheimer's disease, as it cleaves a precursor protein to create the amyloid beta peptide whose aggregates form the senile plaques encountered in the brains of patients. Gamma-secretase is a member of the intramembrane-cleaving proteases which process their transmembrane substrates within the bilayer." ], "exact_answer": [ "cleaves a precursor protein to create the amyloid beta peptide" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "http://www.disease-ontology.org/api/metadata/DOID:10652", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053829" ], "type": "factoid", "id": "58a2c77a60087bc10a000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "gamma-Secretase is critically involved in the Notch pathway and in Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19958468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "Presenilins are the catalytic subunit of the large gamma-secretase complex, that promotes intramembranous proteolysis of the beta-amyloid precursor protein (APP), resulting in the production of beta-amyloid (A beta). Mutant presenilin causes early-onset familial Alzheimer's disease (FAD), is related to abnormal Ca(2+) signaling, and render cells vulnerable to cell death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20035833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "Presenilins form the catalytic part of the gamma-secretases, protein complexes that are responsible for the intramembranous cleavage of transmembrane proteins. The presenilins are involved in several biological functions, but are best known for their role in the generation of the beta-amyloid (Abeta) peptide in Alzheimer's disease and are therefore thought to be important drug targets for this disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129170", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Amyloid-beta peptides (Abeta) generated by proteolysis of the beta-amyloid precursor protein (APP) by beta- and gamma-secretases play an important role in the pathogenesis of Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20600609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "The gamma-secretase complex has a decisive role in the development of Alzheimer's disease, in that it cleaves a precursor to create the amyloid beta peptide whose aggregates form the senile plaques encountered in the brains of patients. Gamma-secretase is a member of the intramembrane-cleaving proteases which process their transmembrane substrates within the bilayer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20445084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The GxxxG motif in the transmembrane domain of AbetaPP plays an essential role in the interaction of CTF beta with the gamma-secretase complex and the formation of amyloid-beta.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625750", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Gamma-secretase-mediated processing of the amyloid-beta protein precursor (AbetaPP) is a crucial step in the formation of the amyloid-beta peptide (Abeta), but little is known about how the substrate AbetaPP interacts with the gamma-secretase complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625750", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 977, "text": "Thus, the present study revealed an essential role for the GxxxG motif in the interaction of AbetaPP with the gamma-secretase complex and the formation of Abeta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625750", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1318, "text": "Taken together, our results suggest an important role of hypoxia in modulating the APP processing by facilitating both beta- and gamma-cleavage which may result in a significant increase of Abeta generation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18063223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The gamma-secretase, composed of presenilin-1 (PS1) or presenilin-2 (PS2), nicastrin (NCT), anterior pharynx-defective phenotype 1 (APH-1), and PEN-2, is critical for the development of Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19376115", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 741, "text": "APP is a ubiquitous membrane protein that is physiologically processed by site-specific proteolysis firstly by alpha- or beta-secretases, releasing a large fragment called APP(S) that contains most of the extracellular sequences of APP, a small extracellular stub, the transmembrane region and the cytoplasmic tail of APP (;AICD'-APP intracellular domain). These are subsequently cleaved by gamma-secretase at multiple sites in the transmembrane region, releasing small peptides, Abeta(1-40) and Abeta(1-42), the major components of AD-associated amyloid fibrils. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19181896", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1108, "text": "As PS1 has been shown to play a critical role in facilitating gamma-secretase activity, and mutations in this protein are associated with familial AD (FAD), we have cloned it from SAMP8 mouse hippocampus and compared its sequence with those of other species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19181896", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1709, "text": "An increased amount or mutation(s) in PS1, which alters the stoichiometric balance of the gamma-secretase complex, may be the cause of aberrant or increased processing of APP, resulting in Abeta accumulation leading to loss of memory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19181896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The gamma-secretase complex plays a role in Alzheimer's disease and cancer progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19299585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The gamma-secretase complex plays a role in Alzheimer's disease and cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19299585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate \u03b3-Secretase Activities", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26559975", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Synthesis and SAR Studies of Fused Oxadiazines as \u03b3-Secretase Modulators for Treatment of Alzheimers Disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900409", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560791", "endSection": "title" }, { "offsetInBeginSection": 500, "offsetInEndSection": 851, "text": "The reconstituted enzyme processes C99 and the Notch-like substrate N160 and displays the characteristic features of gamma-secretase in terms of sensitivity to a gamma-secretase inhibitor, upregulation of Abeta42 production by a familial Alzheimer's disease (FAD) mutation in the APP gene, and downregulation of Notch processing by PS1 FAD mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15766275", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 923, "text": "The Aph1B complex contributes to total gamma-secretase activity in the human brain, and thus specific targeting of Aph1B-containing gamma-secretase complexes may help generate less toxic therapies for Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19299585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Genetic analysis of familial Alzheimer's disease has revealed that mutations in the gamma-secretase enzyme presenilin promote toxic Abeta secretion; however, presenilin mutations might also influence tau hyperphosphorylation and neurodegeneration through gamma-secretase-independent mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16675392", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 728, "text": "Here, we show that familial Alzheimer's disease mutations clustered near the sites of gamma-secretase cleavage actually decrease gamma-secretase-mediated release of the intracellular fragment of APP (CTFgamma). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15992373", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 350, "text": "Beside the well investigated role of presenilins as the catalytic unit in \u03b3-secretase complex, their involvement in regulation of intracellular calcium homeostasis has recently come into more focus of Alzheimer's disease research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23379308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The \u03b3-secretase complex is a promising target in Alzheimer's disease because of its role in the amyloidogenic processing of \u03b2-amyloid precursor protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316412", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 644, "text": "Genetic studies of early-onset familial Alzheimer's disease cases revealed causative mutations in the genes encoding \u03b2-amyloid precursor protein and the \u03b3-secretase-complex components presenilin-1 and presenilin-2, supporting an important role of \u03b2-amyloid in the pathogenesis of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21487536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Assembly, maturation, and trafficking of the gamma-secretase complex in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18393798", "endSection": "title" }, { "offsetInBeginSection": 216, "offsetInEndSection": 352, "text": "Gamma-secretase was first recognized because of its role in the production of Abeta peptides that are pathogenic in Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16804564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Regulation of gamma-secretase activity in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17298085", "endSection": "title" }, { "offsetInBeginSection": 560, "offsetInEndSection": 835, "text": "Drugs that regulate the production of Abeta by inhibiting or modulating gamma-secretase activity could provide a disease-modifying effect on Alzheimer's disease, although recent studies suggest that gamma-secretase plays important roles in cellular signaling including Notch.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18038124", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 924, "text": "The Aph1B complex contributes to total gamma-secretase activity in the human brain, and thus specific targeting of Aph1B-containing gamma-secretase complexes may help generate less toxic therapies for Alzheimer's disease..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19299585", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 458, "text": "The gamma-secretase complex is therefore believed to be critical in the pathogenesis of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17298085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19299585", "endSection": "title" } ] }, { "body": "Which syndromes are associated with heterochromia iridum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25971175", "http://www.ncbi.nlm.nih.gov/pubmed/22174915", "http://www.ncbi.nlm.nih.gov/pubmed/8981698", "http://www.ncbi.nlm.nih.gov/pubmed/6823113", "http://www.ncbi.nlm.nih.gov/pubmed/23840513", "http://www.ncbi.nlm.nih.gov/pubmed/21339912", "http://www.ncbi.nlm.nih.gov/pubmed/7702105", "http://www.ncbi.nlm.nih.gov/pubmed/20199465", "http://www.ncbi.nlm.nih.gov/pubmed/17878817", "http://www.ncbi.nlm.nih.gov/pubmed/1480396", "http://www.ncbi.nlm.nih.gov/pubmed/8092450", "http://www.ncbi.nlm.nih.gov/pubmed/24194866", "http://www.ncbi.nlm.nih.gov/pubmed/12825064", "http://www.ncbi.nlm.nih.gov/pubmed/3792843", "http://www.ncbi.nlm.nih.gov/pubmed/16814183", "http://www.ncbi.nlm.nih.gov/pubmed/16826074", "http://www.ncbi.nlm.nih.gov/pubmed/14166458" ], "ideal_answer": [ "The syndromes that are associated with heterochromia iridum are:\n1) Ascher's syndrome\n2) Waardenburg Syndrome type II (WS2)\n3) Horner's syndrome." ], "exact_answer": [ [ "Ascher's syndrome" ], [ "Waardenburg Syndrome type II", "WS2", "WS Type II" ], [ "Horner's syndrome" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ], "type": "list", "id": "58b52c8822d3005309000001", "snippets": [ { "offsetInBeginSection": 532, "offsetInEndSection": 797, "text": "To our knowledge, this is the first reported case of Ascher's syndrome associated with iris coloboma, heterochromia iridum, and narrowing of horizontal palpebral fissure and decreased outer intercanthal distance secondary to lengthening of lateral canthal ligament.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25971175", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 763, "text": " Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194866", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 815, "text": "The association of congenital Horner's syndrome and hypochromia iridum without anhidrosis is highly suggestive of sympathetic pathway injury early in life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21339912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "The Waardenburg syndrome (WS) consists of at least two distinct autosomal dominant hereditary disorders. WS Type I has been mapped to the distal part of chromosome 2q and the gene identified as PAX3. Other gene(s) are responsible for WS Type II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7702105", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 704, "text": "Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7702105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "WAARDENBURG'S SYNDROME AND HETEROCHROMIA IRIDUM IN A DEAF SCHOOL POPULATION.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14166458", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Waardenburg's syndrome consists of lateral displacement of the inner canthi of the eyes (dystopia canthorum), a broad nasal root and confluent eyebrows, heterochromia iridum, a white forelock and congenital deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14166458", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 793, "text": "To our knowledge, this is the first reported case of Ascher's syndrome associated with iris coloboma, heterochromia iridum, and narrowing of horizontal palpebral fissure and decreased outer intercanthal distance secondary to lengthening of lateral canthal ligament.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25971175", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 698, "text": "Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7702105", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 757, "text": "Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "We present the genetic analyses conducted on a three-generation family (14 individuals) with three members affected with isolated-Hirschsprung disease (HSCR) and one with HSCR and heterochromia iridum (syndromic-HSCR), a phenotype reminiscent of Waardenburg-Shah syndrome (WS4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23840513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Heterochromia iridis and Horner's syndrome due to paravertebral neurilemmoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6823113", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "[Iris heterochromia in acquired Horner's syndrome].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17878817", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BACKGROUND: Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1480396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "A case of heterochromia iridis and Horner's syndrome is reported in a 7-year old girl with paravertebral neurilemmoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6823113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "We present the genetic analyses conducted on a three-generation family (14 individuals) with three members affected with isolated-Hirschsprung disease (HSCR) and one with HSCR and heterochromia iridum (syndromic-HSCR), a phenotype reminiscent of Waardenburg-Shah syndrome (WS4)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23840513", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 794, "text": "To our knowledge, this is the first reported case of Aschers syndrome associated with iris coloboma, heterochromia iridum, and narrowing of horizontal palpebral fissure and decreased outer intercanthal distance secondary to lengthening of lateral canthal ligament", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25971175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "WAARDENBURGS SYNDROME AND HETEROCHROMIA IRIDUM IN A DEAF SCHOOL POPULATION", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14166458", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Waardenburgs syndrome consists of lateral displacement of the inner canthi of the eyes (dystopia canthorum), a broad nasal root and confluent eyebrows, heterochromia iridum, a white forelock and congenital deafness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14166458", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 761, "text": "Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194866", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 763, "text": "Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "A dominantly inherited syndrome associated with hypopigmentation, heterochromia irides, colobomatous eyes and bilateral hearing loss has been ascertained in Fleckvieh cattle (German White Fleckvieh syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22174915", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 703, "text": "Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7702105", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 762, "text": "Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24194866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "WAARDENBURG'S SYNDROME AND HETEROCHROMIA IRIDUM IN A DEAF SCHOOL POPULATION.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14166458", "endSection": "title" } ] }, { "body": "What is the target of tanezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22004765", "http://www.ncbi.nlm.nih.gov/pubmed/18505735", "http://www.ncbi.nlm.nih.gov/pubmed/24452657", "http://www.ncbi.nlm.nih.gov/pubmed/27936977", "http://www.ncbi.nlm.nih.gov/pubmed/25326242", "http://www.ncbi.nlm.nih.gov/pubmed/21130822", "http://www.ncbi.nlm.nih.gov/pubmed/23628600", "http://www.ncbi.nlm.nih.gov/pubmed/21696889", "http://www.ncbi.nlm.nih.gov/pubmed/21420111", "http://www.ncbi.nlm.nih.gov/pubmed/24830649", "http://www.ncbi.nlm.nih.gov/pubmed/24809946", "http://www.ncbi.nlm.nih.gov/pubmed/27381034", "http://www.ncbi.nlm.nih.gov/pubmed/23707270", "http://www.ncbi.nlm.nih.gov/pubmed/24691709", "http://www.ncbi.nlm.nih.gov/pubmed/21802499", "http://www.ncbi.nlm.nih.gov/pubmed/25527221", "http://www.ncbi.nlm.nih.gov/pubmed/25073573", "http://www.ncbi.nlm.nih.gov/pubmed/20942668", "http://www.ncbi.nlm.nih.gov/pubmed/20140821", "http://www.ncbi.nlm.nih.gov/pubmed/23010344", "http://www.ncbi.nlm.nih.gov/pubmed/26962464", "http://www.ncbi.nlm.nih.gov/pubmed/26940379", "http://www.ncbi.nlm.nih.gov/pubmed/25594611", "http://www.ncbi.nlm.nih.gov/pubmed/23028238", "http://www.ncbi.nlm.nih.gov/pubmed/23852695" ], "ideal_answer": [ "Tanezumab is a humanized monoclonal antibody against nerve growth factor." ], "exact_answer": [ "nerve growth factor", "NGF" ], "type": "factoid", "id": "5890e163621ea6ff7e000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27381034", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "OBJECTIVE: To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27381034", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 847, "text": " Current research focuses on the development of new OA drugs (such as sprifermin/recombinant human fibroblast growth factor-18, tanezumab/monoclonal antibody against \u03b2-nerve growth factor), which aims for more effectiveness and less incidence of adverse effects than the traditional ones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26962464", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 775, "text": "Areas covered: This manuscript is a review that examines both the pharmacological properties and clinical studies of tanezumab, the most widely studied antibody to NGF, for management of osteoarthritis (OA) and low back pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27936977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "OBJECTIVE: Evaluate efficacy and safety of tanezumab, a humanized monoclonal antibody against nerve growth factor, in neuropathic pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25594611", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 852, "text": "In preclinical studies, tanezumab, and its murine precursor muMab-911, effectively targeted the NGF pathway in various chronic and inflammatory pain models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140821", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 696, "text": "Tanezumab (RN-624), a first-in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer Inc for the potential treatment of pain associated with several conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140821", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1343, "text": "Given that tanezumab is an antibody, the drug demonstrates the general advantages of this class of products (including good specificity and favorable pharmacokinetics), and also appears to be particularly well suited for targeting the chronic and inflammatory-mediating pain actions of NGF and its receptor system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "In this randomized, double-blind, placebo controlled phase 2 study we investigated tanezumab, a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for interstitial cystitis pain.Patients with interstitial cystitis received a single intravenous dose of 200 \u03bcg/kg tanezumab or placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21420111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Nerve safety of tanezumab, a nerve growth factor inhibitor for pain treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25073573", "endSection": "title" }, { "offsetInBeginSection": 700, "offsetInEndSection": 856, "text": "In preclinical studies, tanezumab, and its murine precursor muMab-911, effectively targeted the NGF pathway in various chronic and inflammatory pain models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140821", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 699, "text": "Tanezumab (RN-624), a first-in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer Inc for the potential treatment of pain associated with several conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140821", "endSection": "abstract" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1350, "text": "Given that tanezumab is an antibody, the drug demonstrates the general advantages of this class of products (including good specificity and favorable pharmacokinetics), and also appears to be particularly well suited for targeting the chronic and inflammatory-mediating pain actions of NGF and its receptor system..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140821", "endSection": "abstract" } ] }, { "body": "Could plasmepsins be used as targets for developing anti-malaria drugs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12767832", "http://www.ncbi.nlm.nih.gov/pubmed/25827401", "http://www.ncbi.nlm.nih.gov/pubmed/21334328", "http://www.ncbi.nlm.nih.gov/pubmed/11841219", "http://www.ncbi.nlm.nih.gov/pubmed/17727268", "http://www.ncbi.nlm.nih.gov/pubmed/16838300", "http://www.ncbi.nlm.nih.gov/pubmed/15181345", "http://www.ncbi.nlm.nih.gov/pubmed/19472268", "http://www.ncbi.nlm.nih.gov/pubmed/21136953", "http://www.ncbi.nlm.nih.gov/pubmed/14636976", "http://www.ncbi.nlm.nih.gov/pubmed/8816746", "http://www.ncbi.nlm.nih.gov/pubmed/26214367", "http://www.ncbi.nlm.nih.gov/pubmed/24975562", "http://www.ncbi.nlm.nih.gov/pubmed/23466235", "http://www.ncbi.nlm.nih.gov/pubmed/16054370", "http://www.ncbi.nlm.nih.gov/pubmed/12435452", "http://www.ncbi.nlm.nih.gov/pubmed/16138859", "http://www.ncbi.nlm.nih.gov/pubmed/15011947", "http://www.ncbi.nlm.nih.gov/pubmed/25719272", "http://www.ncbi.nlm.nih.gov/pubmed/22242846", "http://www.ncbi.nlm.nih.gov/pubmed/21382523", "http://www.ncbi.nlm.nih.gov/pubmed/20056606", "http://www.ncbi.nlm.nih.gov/pubmed/24468190", "http://www.ncbi.nlm.nih.gov/pubmed/26566224", "http://www.ncbi.nlm.nih.gov/pubmed/19437467", "http://www.ncbi.nlm.nih.gov/pubmed/9561244", "http://www.ncbi.nlm.nih.gov/pubmed/21760810", "http://www.ncbi.nlm.nih.gov/pubmed/17585371", "http://www.ncbi.nlm.nih.gov/pubmed/24983235", "http://www.ncbi.nlm.nih.gov/pubmed/27718413", "http://www.ncbi.nlm.nih.gov/pubmed/21428877", "http://www.ncbi.nlm.nih.gov/pubmed/18442137" ], "ideal_answer": [ "Yes, plasmepsins, which are essential Plasmodium proteases, could be highly promising anti-malarial drug targets." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000962", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015195", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008288", "http://www.disease-ontology.org/api/metadata/DOID:12365", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016780" ], "type": "yesno", "id": "58a6d89660087bc10a00002b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Fighting malaria: structure-guided discovery of nonpeptidomimetic plasmepsin inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25719272", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 274, "text": "Given that the parasite needs the resulting amino acid building blocks for its growth and development, plasmepsins are an important antimalarial drug target. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25719272", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 1056, "text": "Due to early crystallographic evidence, plasmepsin II (Plm II) emerged as well explored target to develop novel antimalarials as well as a starting point to develop inhibitors targeting some other subtypes of plasmepsins i.e. Plm I, II, IV and V. With the advancements in drug discovery, several computational and synthetic approaches were employed in order to develop novel inhibitors targeting Plm II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26214367", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Plasmepsin V, an essential aspartyl protease of malaria parasites, has a key role in the export of effector proteins to parasite-infected erythrocytes. Consequently, it is an important drug target for the two most virulent malaria parasites of humans, Plasmodium falciparum and Plasmodium vivax.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26214367", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 388, "text": "Plasmepsin V (PmV) is an essential Plasmodium protease and a highly promising antimalarial target, which still lacks molecular characterization and drug-like inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26566224", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1503, "text": "Our inhibitors act 'on-target', confirmed by cellular interference of PmV function and biochemical interaction with inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26566224", "endSection": "abstract" }, { "offsetInBeginSection": 1826, "offsetInEndSection": 2191, "text": "Our work disclosed novel pursuable drug design strategies for highly efficient PmV inhibition highlighting novel molecular elements necessary for picomolar activity against PmV. All the presented data are discussed in respect to human aspartic proteases and previously reported inhibitors, highlighting differences and proposing new strategies for drug development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26566224", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 458, "text": "High binding likeness on antimalarial target plasmepsin was detected through molecular docking. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24975562", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1303, "text": "This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp. and for parasite survival in human erythrocytes and validates PMV as an antimalarial drug target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983235", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 310, "text": "The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease, Plasmepsin V (PMV). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Plasmepsin II (PM II) is an attractive target for anti-malaria drug discovery, which involves in host hemoglobin degradation in the acidic food vacuole.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466235", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 480, "text": "These methods are utilized to search for inhibitors of the aspartyl proteases, plasmepsin II and cathepsin D. Plasmepsin II, a protease found in the malaria parasite, hydrolyzes human hemoglobin, the nutrient source for the parasite and is a new target for anti-malaria therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9561244", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 1040, "text": "Given recent advances in understanding the fundamental roles of the various plasmepsins, it is likely that the most effective antimalarial plasmepsin targets will be the non-digestive vacuole plasmepsins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22242846", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Plasmepsins (PMs) are essential proteases of the plasmodia parasites and are therefore promising targets for developing drugs against malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19472268", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 274, "text": "Therefore, the plasmepsins of malaria parasites have been recognized as attractive antimalarial drug targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21334328", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 201, "text": "As inhibition of plasmepsins leads to the parasite's death, these enzymes can be utilized as potential drug targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16138859", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 515, "text": "falciparum plasmepsins II and IV make structure-based drug design of antimalarial compounds that focus on inhibiting plasmepsins possible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18442137", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 462, "text": "The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8816746", "endSection": "abstract" }, { "offsetInBeginSection": 1906, "offsetInEndSection": 2052, "text": "vivax plasmepsins (PvPMs) from different geographical regions are of utmost importance for drugs and vaccine designs for anti-malarial strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21382523", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 345, "text": "In P.falciparum, plasmepsins I, II, IV and HAP have been directly implicated in hemoglobin degradation during malaria infection, and are now considered targets for anti-malarial drug design.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12767832", "endSection": "abstract" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1743, "text": "These results shed light on the role of V105 and T108 residues in plasmepsin specificities, and they should be useful in structure-based design of novel, selective inhibitors that may serve as antimalarial drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18442137", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 245, "text": "The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21760810", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 994, "text": "A large compound library of about 1 million chemical compounds was docked on 5 different targets of plasmepsins using two different docking software, namely FlexX and AutoDock.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17727268", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 281, "text": "Plasmodium aspartic proteases known as plasmepsins play an important role on haemoglobin degradation and are being studied as drug targets for chemotherapy of malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14636976", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 815, "text": "Our study revealed about 100 parasite-coded gene products that included many known drug targets such as Pf hypoxanthine guanine phosphoribosyl transferase, Pf L-lactate dehydrogenase, and Plasmepsins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21136953", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 295, "text": "The two aspartic proteases, plasmepsins I and II, from Plasmodium falciparum have recently emerged as potential targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16054370", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 303, "text": "Plasmepsins are highly promising as drug targets, especially when combined with the inhibition of falcipains that are also involved in hemoglobin catabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17585371", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1133, "text": "Among such enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine proteases) are highly promising antimalarial drug targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21428877", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 878, "text": "The high sequence conservations between the plasmepsins from the isolates support the notion that the enzymes could be reliable targets for new antimalarial chemotherapeutics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15181345", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 877, "text": "Due to early crystallographic evidence, plasmepsin II (Plm II) emerged as well explored target to develop novel antimalarials as well as a starting point to develop inhibitors targeting some other subtypes of plasmepsins i.e.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827401", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 651, "text": "Plasmepsin, an aspartic protease, which is involved in the hemoglobin breakdown into smaller peptides emerged as a crucial target to develop new chemical entities to counter malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827401", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1233, "text": "were employed in order to develop new chemical entities targeting Plm II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827401", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1055, "text": "With the advancements in drug discovery, several computational and synthetic approaches were employed in order to develop novel inhibitors targeting Plm II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827401", "endSection": "abstract" }, { "offsetInBeginSection": 1906, "offsetInEndSection": 2053, "text": "vivax plasmepsins (PvPMs) from different geographical regions are of utmost importance for drugs and vaccine designs for anti-malarial strategies..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21382523", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 422, "text": "We developed a potent inhibitor of plasmepsin V, called WEHI-842, which directly mimics the Plasmodium export element (PEXEL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26214367", "endSection": "abstract" }, { "offsetInBeginSection": 1768, "offsetInEndSection": 1905, "text": "In order to validate appropriate use of PM4 as potential anti-malarial drug target, studies on genetic and structural variations among P.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21382523", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 642, "text": "Over the past decade, much effort has been placed towards developing plasmepsin inhibitors as antimalarial agents, particularly targeting the digestive vacuole.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22242846", "endSection": "abstract" } ] }, { "body": "What is MRSA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18347206", "http://www.ncbi.nlm.nih.gov/pubmed/8851953", "http://www.ncbi.nlm.nih.gov/pubmed/26684366", "http://www.ncbi.nlm.nih.gov/pubmed/22291965", "http://www.ncbi.nlm.nih.gov/pubmed/15472807", "http://www.ncbi.nlm.nih.gov/pubmed/24267132", "http://www.ncbi.nlm.nih.gov/pubmed/27025639", "http://www.ncbi.nlm.nih.gov/pubmed/25240872", "http://www.ncbi.nlm.nih.gov/pubmed/17581935", "http://www.ncbi.nlm.nih.gov/pubmed/15884297", "http://www.ncbi.nlm.nih.gov/pubmed/27721155", "http://www.ncbi.nlm.nih.gov/pubmed/27112442", "http://www.ncbi.nlm.nih.gov/pubmed/19130105", "http://www.ncbi.nlm.nih.gov/pubmed/19777772", "http://www.ncbi.nlm.nih.gov/pubmed/21075466", "http://www.ncbi.nlm.nih.gov/pubmed/19732087", "http://www.ncbi.nlm.nih.gov/pubmed/19162372", "http://www.ncbi.nlm.nih.gov/pubmed/27736763", "http://www.ncbi.nlm.nih.gov/pubmed/21571749", "http://www.ncbi.nlm.nih.gov/pubmed/19252301", "http://www.ncbi.nlm.nih.gov/pubmed/23756924", "http://www.ncbi.nlm.nih.gov/pubmed/23824338", "http://www.ncbi.nlm.nih.gov/pubmed/24322533", "http://www.ncbi.nlm.nih.gov/pubmed/22814471", "http://www.ncbi.nlm.nih.gov/pubmed/19129414", "http://www.ncbi.nlm.nih.gov/pubmed/20071545", "http://www.ncbi.nlm.nih.gov/pubmed/26047024", "http://www.ncbi.nlm.nih.gov/pubmed/25108628", "http://www.ncbi.nlm.nih.gov/pubmed/26812054", "http://www.ncbi.nlm.nih.gov/pubmed/22176801", "http://www.ncbi.nlm.nih.gov/pubmed/27450316", "http://www.ncbi.nlm.nih.gov/pubmed/23405883", "http://www.ncbi.nlm.nih.gov/pubmed/24850346", "http://www.ncbi.nlm.nih.gov/pubmed/25648247", "http://www.ncbi.nlm.nih.gov/pubmed/19828738", "http://www.ncbi.nlm.nih.gov/pubmed/25865979", "http://www.ncbi.nlm.nih.gov/pubmed/20861339", "http://www.ncbi.nlm.nih.gov/pubmed/19710260", "http://www.ncbi.nlm.nih.gov/pubmed/25113379", "http://www.ncbi.nlm.nih.gov/pubmed/12723397", "http://www.ncbi.nlm.nih.gov/pubmed/17385151", "http://www.ncbi.nlm.nih.gov/pubmed/24045390", "http://www.ncbi.nlm.nih.gov/pubmed/19506056", "http://www.ncbi.nlm.nih.gov/pubmed/15060266", "http://www.ncbi.nlm.nih.gov/pubmed/20524852", "http://www.ncbi.nlm.nih.gov/pubmed/20071548", "http://www.ncbi.nlm.nih.gov/pubmed/17537949", "http://www.ncbi.nlm.nih.gov/pubmed/17121622" ], "ideal_answer": [ "community-associated methicillin resistant staphylococcus aureus (ca-mrsa) has become a severe health concern because of its treatment difficulties.", "Methicillin resistant Staphylococcus aureus (MRSA) has become a severe health concern because of its treatment difficulties.", "(MRSA, methicillin-resistant S. aureus)" ], "exact_answer": [ "methicillin-resistant S. aureus", "MRSA" ], "type": "factoid", "id": "58a32efe60087bc10a000013", "snippets": [ { "offsetInBeginSection": 137, "offsetInEndSection": 176, "text": "(MRSA, methicillin-resistant S. aureus)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27736763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has become a severe health concern because of its treatment difficulties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27721155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "We investigated the distribution of MRSA (methicillin-resistant Staphylococcus aureus) on and around six patients with MRSA infection in our neurosurgical ward.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8851953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The aim of this study was to assess to what extent patients with meticillin-resistant Staphylococcus aureus (MRSA) at respiratory sites shed viable MRSA into the air of hospital rooms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19162372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasing in prevalence among asymptomatic carriers and in cases of paediatric soft-tissue infections alike.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24322533", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 875, "text": "Most of MRSA strains and a part of methicillin-susceptible S. aureus (MSSA) strains harbored unique combinations of non-\u00df-lactamase genes aac(6)/aph(2\u2033), aph(3)-III, ant (4,4\u2033), ermA, ermC, mrsA, tetM, and tetK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23405883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSAs Multiple Virulence Factors, Genome, and Stepwise Evolution", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26047024", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "It was found in the present study that combined use of fusidic acid (FA) and berberine chloride (BBR) offered an in vitro synergistic action against 7 of the 30 clinical methicillin-resistant Staphylococcus aureus (MRSA) strains, with a fractional inhibitory concentration (FIC) index ranging from 0.5 to 0.19", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25108628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Vancomycin MIC creep in methicillin-resistant Staphylococcus aureus (MRSA) isolates from 2006 to 2010 in a hospital in China", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25865979", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "To assess whether vancomycin minimum inhibitory concentration (MIC) creeps among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in a regional hospital in China", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25865979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Detection of methicillin-resistant Staphylococcus aureus (MRSA) in specimens from various body sites: performance characteristics of the BD GeneOhm MRSA assay, the Xpert MRSA assay, and broth-enriched culture in an area with a low prevalence of MRSA infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20861339", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Rapid detection of Methicillin-Resistant Staphylococcus aureus MRSA in nose, groin, and axilla swabs by the BD GeneOhm MRSA achromopeptidase assay and comparison with culture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23756924", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Methicillin-resistant Staphylococcus aureus (MRSA) detection: comparison of two molecular methods (IDI-MRSA PCR assay and GenoType MRSA Direct PCR assay) with three selective MRSA agars (MRSA ID, MRSASelect, and CHROMagar MRSA) for use with infection-control swabs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17537949", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Comparison of the Xpert methicillin-resistant Staphylococcus aureus (MRSA) assay, BD GeneOhm MRSA assay, and culture for detection of nasal and cutaneous groin colonization by MRSA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19710260", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Comparison of the BD Max methicillin-resistant Staphylococcus aureus (MRSA) assay and the BD GeneOhm MRSA achromopeptidase assay with direct- and enriched-culture techniques using clinical specimens for detection of MRSA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22814471", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Comparison of MRSASelect Agar, CHROMagar Methicillin-Resistant Staphylococcus aureus (MRSA) Medium, and Xpert MRSA PCR for detection of MRSA in Nares: diagnostic accuracy for surveillance samples with various bacterial densities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19828738", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) in diverse clinical specimens by the BD GeneOhm MRSA assay and comparison with culture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20071545", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Multicenter evaluation of the Cepheid Xpert methicillin-resistant Staphylococcus aureus (MRSA) test as a rapid screening method for detection of MRSA in nares.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19129414", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Prospective comparison of the clinical impacts of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19506056", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Long-term control of endemic hospital-wide methicillin-resistant Staphylococcus aureus (MRSA): the impact of targeted active surveillance for MRSA in patients and healthcare workers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20524852", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Methicillin-resistant Staphylococcus aureus (MRSA) infections pose a major challenge in health care, yet the limited heterogeneity within this group hinders molecular investigations of related outbreaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24850346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "In a previous study, we reported that two kaempferol glycosides isolated from Laurus nobilis L., kaempferol-3-O-alpha-L-(2'',4''-di-E-p-coumaroyl)-rhamnoside (C2) and kaempferol-3-O-alpha-L-(2''-E-p-coumaroyl-4''-Z-p-coumaroyl)-rhamnoside (C3), showed strong antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19252301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "This article explains what methicillin-resistant Staphylococcus aureus (MRSA) is, how it is spread and what the real challenges are in healthcare settings in the UK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15884297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging threat to public health, especially in correctional settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21571749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "There are few more compelling questions in clinical microbiology today than the issue of whether or not to screen for the presence of methicillin-resistant Staphylococcus aureus (MRSA), with the results being used to institute infection control interventions aimed at preventing transmission of MRSA in health care environments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20071548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Methicillin-resistant Staphylococcus aureus (MRSA) detection: comparison of two molecular methods (IDI-MRSA PCR assay and GenoType MRSA Direct PCR assay) with three selective MRSA agars (MRSA ID, MRSASelect, and CHROMagar MRSA) for use with infection-control swabs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17537949", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Do methicillin resistant staphylococcus (MRSA) carrier patients influence MRSA infection more than MRSA-carrier medical officers and MRSA-carrier family?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045390", "endSection": "title" }, { "offsetInBeginSection": 126, "offsetInEndSection": 176, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19732087", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 142, "text": " methicillin-resistant Staphylococcus aureus (CA-MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15060266", "endSection": "abstract" }, { "offsetInBeginSection": 45, "offsetInEndSection": 96, "text": "methicillin-resistant Staphylococcus aureus (MRSA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19130105", "endSection": "abstract" }, { "offsetInBeginSection": 23, "offsetInEndSection": 84, "text": "methicillin-resistant Staphylococcus aureus (MRSA) infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23824338", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 86, "text": "methicillin resistant Staphylococcus aureus (MRSA CC398) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21075466", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 190, "text": " (methicillin-resistant Staphylococcus aureus) MRSA ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25113379", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 62, "text": "Methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27450316", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 399, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26812054", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 122, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17385151", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 116, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24267132", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 105, "text": "methicillin-resistant Staphylococcus aureus (MRSA) ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17581935", "endSection": "title" }, { "offsetInBeginSection": 60, "offsetInEndSection": 110, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347206", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Methicillin-resistant Staphylococcus aureus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22176801", "endSection": "title" }, { "offsetInBeginSection": 65, "offsetInEndSection": 116, "text": " methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25648247", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 86, "text": "methicillin-resistant Staphylococcus aureus-(CA-MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22291965", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 446, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25240872", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 134, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12723397", "endSection": "title" }, { "offsetInBeginSection": 45, "offsetInEndSection": 95, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26684366", "endSection": "title" }, { "offsetInBeginSection": 73, "offsetInEndSection": 123, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26684366", "endSection": "abstract" }, { "offsetInBeginSection": 58, "offsetInEndSection": 111, "text": "methicillin-resistant Staphylococcus aureus (HA-MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27025639", "endSection": "abstract" }, { "offsetInBeginSection": 43, "offsetInEndSection": 94, "text": "methicillin-resistant Staphylococcus aureus (MRSA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15472807", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 280, "text": "methicillin-resistant Staphylococcus aureus (MRSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17121622", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 102, "text": "methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27112442", "endSection": "abstract" } ] }, { "body": "List peptide fragmentations methods in mass spectrometry", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26780731", "http://www.ncbi.nlm.nih.gov/pubmed/27613306", "http://www.ncbi.nlm.nih.gov/pubmed/27914015", "http://www.ncbi.nlm.nih.gov/pubmed/27139140", "http://www.ncbi.nlm.nih.gov/pubmed/27098412", "http://www.ncbi.nlm.nih.gov/pubmed/27520322" ], "ideal_answer": [ "CID, HCD, ECD, ETD and PSD are different peptide fragmentation technologies used in mass spectrometry." ], "exact_answer": [ [ "CID", "collision-induced dissociation" ], [ "HCD", "Higher-energy collisional dissociation" ], [ "ECD", "electron capture dissociation" ], [ "ETD", "electron transfer dissociation" ], [ "PSD", "post-source decay" ] ], "type": "list", "id": "58a8071760087bc10a000037", "snippets": [ { "offsetInBeginSection": 585, "offsetInEndSection": 632, "text": " using the CID and HCD fragmentation techniques", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26780731", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 982, "text": "By integrating HCD-MS/MS, CID-MS/MS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27139140", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 840, "text": "ECD and ETD induced different fragmentation processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27098412", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 496, "text": "MALDI post-source decay (PSD), MALDI 157 nm photodissociation, tris(2,4,6-trimethoxyphenyl)phosphonium bromide (TMPP) charge tagging in PSD and photodissociation, ESI collision-induced dissociation (CID), electron transfer dissociation (ETD), and free-radical initiated peptide sequencing (FRIPS) with CID were applied to peptides containing either aspartic or isoaspartic acid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27613306", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 705, "text": "automated analysis of HCD and ETD fragmentation spectra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27520322", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1147, "text": "The combination of DIA analysis and ETD fragmentation with supplemental CID energy ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914015", "endSection": "abstract" } ] }, { "body": "Is avanafil indicated for treatment of erectile dysfunction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23321580", "http://www.ncbi.nlm.nih.gov/pubmed/27121186", "http://www.ncbi.nlm.nih.gov/pubmed/25591992", "http://www.ncbi.nlm.nih.gov/pubmed/25684196", "http://www.ncbi.nlm.nih.gov/pubmed/22704456", "http://www.ncbi.nlm.nih.gov/pubmed/23521325", "http://www.ncbi.nlm.nih.gov/pubmed/23955441", "http://www.ncbi.nlm.nih.gov/pubmed/22448738", "http://www.ncbi.nlm.nih.gov/pubmed/22857780", "http://www.ncbi.nlm.nih.gov/pubmed/22248153", "http://www.ncbi.nlm.nih.gov/pubmed/23219537", "http://www.ncbi.nlm.nih.gov/pubmed/22788525", "http://www.ncbi.nlm.nih.gov/pubmed/25455484", "http://www.ncbi.nlm.nih.gov/pubmed/24589460", "http://www.ncbi.nlm.nih.gov/pubmed/26784833", "http://www.ncbi.nlm.nih.gov/pubmed/22759639", "http://www.ncbi.nlm.nih.gov/pubmed/27377089", "http://www.ncbi.nlm.nih.gov/pubmed/25801159", "http://www.ncbi.nlm.nih.gov/pubmed/25582903", "http://www.ncbi.nlm.nih.gov/pubmed/24259695", "http://www.ncbi.nlm.nih.gov/pubmed/24331245", "http://www.ncbi.nlm.nih.gov/pubmed/26316720", "http://www.ncbi.nlm.nih.gov/pubmed/24701971", "http://www.ncbi.nlm.nih.gov/pubmed/23590161" ], "ideal_answer": [ "Yes, avanafil is indicated for treatment of erectile dysfunction." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.biosemantics.org/jochem#4243720", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007172" ], "type": "yesno", "id": "5895d0457d9090f35300000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "CONTEXT: Avanafil (AVA) is used in the treatment of erectile dysfunction, but is reported for its poor aqueous solubility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26784833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27121186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "A survey on the experience of 136 Italian urologists in the treatment of erectile dysfunction with PDE5 inhibitors and recommendations for the use of Avanafil in the clinical practice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27377089", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25591992", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "PURPOSE: We examined the therapeutic effects of avanafil 15 minutes after dosing in men with mild to severe erectile dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25591992", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 440, "text": "Sildenafil, vardenafil, tadalafil and avanafil are FDA approved drugs in market as PDE5 inhibitors for treating erectile dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25801159", "endSection": "abstract" }, { "offsetInBeginSection": 1428, "offsetInEndSection": 1711, "text": "CONCLUSION: Avanafil along with the other PDE5Is has shown to be a safe and effective oral treatment for ED, with avanafil's possible place in therapy for patients who want an on-demand option or as an alternative in patients who experience visual disturbances with the other agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26316720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Avanafil (STENDRA\u2122, SPEDRA\u2122, Zepeeed\u2122) is an oral phosphodiesterase type 5 inhibitor indicated for the treatment of erectile dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955441", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 669, "text": "In a 12-week, randomized, double-blind, placebo-controlled, multicentre trial in patients with erectile dysfunction, avanafil 50, 100 and 200 mg recipients had significantly greater improvements from baseline than placebo recipients in mean international index of erectile dysfunction-erectile function domain scores and in successful vaginal penetration and sexual intercourse attempts (coprimary endpoints).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Avanafil for the treatment of erectile dysfunction. An updated review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25582903", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: implications for clinical safety and improved tolerability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22759639", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22248153", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Avanafil, a potent and highly selective phosphodiesterase-5 inhibitor for erectile dysfunction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704456", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Avanafil, a highly selective phosphodiesterase type 5 inhibitor for erectile dysfunction, shows good safety profiles for retinal function and hemodynamics in anesthetized dogs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23321580", "endSection": "title" }, { "offsetInBeginSection": 1809, "offsetInEndSection": 1912, "text": "Cumulative data suggest that avanafil has a promising pharmacological profile for erectile dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704456", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1630, "text": "These findings suggest that intracavernosal administration of avanafil might be beneficial for the treatment of erectile dysfunction in patients with T2DM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24331245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23521325", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24331245", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23219537", "endSection": "title" }, { "offsetInBeginSection": 118, "offsetInEndSection": 246, "text": "Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22448738", "endSection": "abstract" }, { "offsetInBeginSection": 1259, "offsetInEndSection": 1546, "text": "Adverse events most commonly reported with avanafil treatment were headache, nasopharyngitis, flushing, and sinus congestion.Avanafil was safe and effective for treating erectile dysfunction in men with diabetes and was effective as early as 15 minutes and more than 6 hours after dosing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22857780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Avanafil (STENDRA\u2122, SPEDRA\u2122, Zepeeed\u2122) is an oral phosphodiesterase type 5 inhibitor indicated for the treatment of erectile dysfunction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955441", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 670, "text": "Avanafil is rapidly absorbed after oral administration, with a median time to maximum plasma concentration of 30 to 45 min. In a 12-week, randomized, double-blind, placebo-controlled, multicentre trial in patients with erectile dysfunction, avanafil 50, 100 and 200 mg recipients had significantly greater improvements from baseline than placebo recipients in mean international index of erectile dysfunction-erectile function domain scores and in successful vaginal penetration and sexual intercourse attempts (coprimary endpoints)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "A phase II, single-blind, randomized, crossover evaluation of the safety and efficacy of avanafil using visual sexual stimulation in patients with mild to moderate erectile dysfunction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22788525", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "To evaluate the safety, efficacy and time course of three doses of avanafil (50 mg, 100 mg and 200 mg) compared with sildenafil 50 mg or placebo, given in conjunction with visual sexual stimulation (VSS) videos in men with mild to moderate erectile dysfunction (ED).Male patients, 35-70 years of age, with mild to moderate ED of \u22656 months duration, were included in the study", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22788525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "Avanafil for erectile dysfunction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259695", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "To review the pharmacology, pharmacokinetics, safety, and efficacy of avanafil and evaluate relevant clinical trial data.A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (1966 to July 2013) were conducted using the key words: avanafil, erectile dysfunction, and phosphodiesterase type 5 (PDE5) inhibitor.Articles evaluating avanafil for erectile dysfunction (ED) published in English and using human subjects were selected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259695", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1305, "text": "In trials in patients with erectile dysfunction in association with diabetes mellitus, and after nerve-sparing radical prostatectomy, avanafil 100 or 200 mg was significantly more efficacious than placebo for primary and most secondary endpoints", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23955441", "endSection": "abstract" }, { "offsetInBeginSection": 1321, "offsetInEndSection": 1864, "text": "However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p <0.05).Data suggest that avanafil has a favorable safety profile for erectile dysfunction, which is attributable to its high inhibitory selectivity for phosphodiesterase type 5 against type 6 (retina) and 1 (vessels, etc), respectively, and its short acting pharmacodynamic property.Copyright \u00a9 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.Copyright \u00a9 2014 Elsevier Inc. All rights reserved.1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19388819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14693562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "To assess the potential of polymeric nanoparticles (NPs) to affect the genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV microbicide drug candidate dapivirine after vaginal delivery.Dapivirine-loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation method", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24449442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14693562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18086845", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1144, "text": "CONCLUSIONS: The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23177261", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 740, "text": "Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges.ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26061040", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 774, "text": "Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19029331", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 829, "text": "Two large efficacy trials of a vaginal ring containing the investigational drug dapivirine demonstrated efficacy and safety in preventing HIV infections in women in Africa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27398859", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 831, "text": "In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23965226", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1611, "text": "Plasma dapivirine concentrations were low (<1 ng/ml) and remained well below those observed at the maximum tolerated dose for oral treatment (mean Cmax of 2286 \u200ang/ml).CONCLUSION: The dapivirine vaginal ring has a safety and pharmacokinetic profile that supports its use as a sustained-release topical microbicide for HIV-1 prevention in women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24901365", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 741, "text": "ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26061040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Dual segment polyurethane intravaginal rings (IVRs) were fabricated to enable sustained release of antiretroviral agents dapivirine and tenofovir to prevent the male to female sexual transmission of the human immunodeficiency virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19958831", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1095, "text": "The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23177261", "endSection": "abstract" } ] }, { "body": "What is Bexsero?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26853725", "http://www.ncbi.nlm.nih.gov/pubmed/25043395", "http://www.ncbi.nlm.nih.gov/pubmed/26603630", "http://www.ncbi.nlm.nih.gov/pubmed/27109566", "http://www.ncbi.nlm.nih.gov/pubmed/27808594", "http://www.ncbi.nlm.nih.gov/pubmed/27923519", "http://www.ncbi.nlm.nih.gov/pubmed/23472347", "http://www.ncbi.nlm.nih.gov/pubmed/25161192", "http://www.ncbi.nlm.nih.gov/pubmed/26686570", "http://www.ncbi.nlm.nih.gov/pubmed/25713028", "http://www.ncbi.nlm.nih.gov/pubmed/26788734", "http://www.ncbi.nlm.nih.gov/pubmed/26788735", "http://www.ncbi.nlm.nih.gov/pubmed/21615224", "http://www.ncbi.nlm.nih.gov/pubmed/27163398", "http://www.ncbi.nlm.nih.gov/pubmed/26304221", "http://www.ncbi.nlm.nih.gov/pubmed/25301037", "http://www.ncbi.nlm.nih.gov/pubmed/27002504", "http://www.ncbi.nlm.nih.gov/pubmed/25368410", "http://www.ncbi.nlm.nih.gov/pubmed/26379162", "http://www.ncbi.nlm.nih.gov/pubmed/27573083", "http://www.ncbi.nlm.nih.gov/pubmed/27521232", "http://www.ncbi.nlm.nih.gov/pubmed/25986879", "http://www.ncbi.nlm.nih.gov/pubmed/23811804", "http://www.ncbi.nlm.nih.gov/pubmed/24631075", "http://www.ncbi.nlm.nih.gov/pubmed/26068564", "http://www.ncbi.nlm.nih.gov/pubmed/26433141", "http://www.ncbi.nlm.nih.gov/pubmed/24141209", "http://www.ncbi.nlm.nih.gov/pubmed/23575646", "http://www.ncbi.nlm.nih.gov/pubmed/24815780", "http://www.ncbi.nlm.nih.gov/pubmed/24462403", "http://www.ncbi.nlm.nih.gov/pubmed/22426368", "http://www.ncbi.nlm.nih.gov/pubmed/27302338", "http://www.ncbi.nlm.nih.gov/pubmed/25325113", "http://www.ncbi.nlm.nih.gov/pubmed/23954380", "http://www.ncbi.nlm.nih.gov/pubmed/24807056", "http://www.ncbi.nlm.nih.gov/pubmed/24284038", "http://www.ncbi.nlm.nih.gov/pubmed/26487381", "http://www.ncbi.nlm.nih.gov/pubmed/26126001", "http://www.ncbi.nlm.nih.gov/pubmed/25882169" ], "ideal_answer": [ "Bexsero is a 4-component vaccine against capsular Meningococcus serogroup B (4CMenB), which has recently been licensed in Europe, Canada and Australia.", "Bexsero is amulticomponent vaccine against serogroup B Neisseria meningitidis (MenB)." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008585", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008589", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065288", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022401", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D038541", "http://www.disease-ontology.org/api/metadata/DOID:13668" ], "type": "summary", "id": "589af57a78275d0c4a000038", "snippets": [ { "offsetInBeginSection": 529, "offsetInEndSection": 662, "text": "A capsular group B meningococcal vaccine - 4CMenB (Bexsero) - has recently been licensed in the European Union, Canada and Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26126001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The 4-component meningococcal serogroup B vaccine 4CMenB (Bexsero) is the first vaccine against this serogroup and has been approved by licensing authorities in Europe, Canada and Australia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26379162", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 149, "text": "Implementation of meningococcal B vaccination (Bexsero\u00ae) in France: Physicians' perceptions and experiences of a few months after marketing approval", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26603630", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 215, "text": "In December 2013, the French public health authorities recommended the use of Bexsero\u00ae (meningococcus B vaccine) in areas with endemic risk and for patients at risk for invasive meningococcal B disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26603630", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 47, "text": "Bexsero, a novel vaccine against meningococcus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26853725", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Meningococcus B is the most prevalent Neisseria meningitidis serogroup isolated in Hungary. Bexsero is one of the vaccines developed against it, which has been available in Hungary since the summer of 2014. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26853725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Vaccinating Italian infants with a new multicomponent vaccine (Bexsero\u00ae) against meningococcal B disease: A cost-effectiveness analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27163398", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero\u00ae) for use in individuals of 2 months of age and older.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27163398", "endSection": "abstract" }, { "offsetInBeginSection": 1620, "offsetInEndSection": 1856, "text": "Our results suggest that vaccinating infants in Italy with Bexsero\u00ae has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27163398", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 802, "text": "Since the antigens selected for Bexsero\u00ae are also harbored by meningococci belonging to other serogroups there may be the potential for Bexsero\u00ae to offer a certain level of protection against non-B serogroups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26788735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "[Bexsero, a novel vaccine against meningococcus].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26853725", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 506, "text": "The new available vaccines are Bexsero\u00ae and Trumenba\u00ae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26788734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Surface-expressed protein antigens such as factor H-binding protein (fHbp), Neisserial adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and Porin protein A (PorA); all express sequence variability that can affect their function as protective immunogens when used in meningococcal serogroup B vaccines like the recently-approved 4CMenB (Bexsero(\u00ae)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24631075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Proteinaceous meningococcal B vaccines are under development, and the most advanced, Bexsero, is currently being evaluated by the European Medicines Agency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472347", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 468, "text": "Among them, the Reverse Vaccinology approach was successfully applied to the development of an innovative vaccine against Neisseria meningitidis serogroup B, now available on the market with the commercial name BEXSERO\u00ae (Novartis Vaccines).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25368410", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 516, "text": "Recently, a vaccine, 4CMenB (Bexsero(\u00ae)), containing three recombinant proteins, and outer membrane vesicles (OMV) derived from a serogroup B meningococcal strain (MenB) has been licensed in Europe and Australia and is indicated for persons aged 2 mo or older.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero(\u00ae)) is a unique vaccine containing four main immunogenic components: three recombinant proteins combined with outer membrane vesicles derived from meningococcal NZ98/254 strain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23575646", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 453, "text": "Recently, a universal serogroup B meningococcal vaccine, Bexsero(\u00ae), was licensed in Europe, Australia and United States, following several clinical studies demonstrating its immunogenicity and safety", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25986879", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 992, "text": "Like any drug, Bexsero(\u00ae) and Trumemba(\u00ae) will require close observation to assess their impact on meningococcal epidemiology. Copyright \u00a9 2015 Elsevier Masson SAS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25986879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Bexsero, a new vaccine against Neisseria meningitidis serogroup B (MenB), is composed of 3 main recombinant proteins and an outer membrane vesicle component", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25713028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The meningococcal 4CMenB vaccine (Bexsero; Novartis) contains four antigens that can elicit serum bactericidal activity, one of which is factor H (FH)-binding protein (FHbp)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25161192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "In December 2013 Bexsero\u00ae became available in Germany for vaccination against serogroup B meningococci (MenB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26487381", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 495, "text": "Bexsero\u00ae is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26487381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Re-evaluating cost effectiveness of universal meningitis vaccination (Bexsero) in England: modelling study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301037", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Bexsero: a multicomponent vaccine for prevention of meningococcal disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426368", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "OBJECTIVE: To use mathematical and economic models to predict the epidemiological and economic impact of vaccination with Bexsero, designed to protect against group B meningococcal disease, to help inform vaccine policy in the United Kingdom.DESIGN: Modelling study.SETTING: England.POPULATION: People aged 0-99.INTERVENTIONS: Incremental impact of introductory vaccine strategies simulated with a transmission dynamic model of meningococcal infection and vaccination including potential herd effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using a recently-licensed, multi-component, protein-based vaccine (Bexsero(\ufffd)).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25043395", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Modelled evaluation of multi-component meningococcal vaccine (Bexsero\u00ae) for the prevention of invasive meningococcal disease in infants and adolescents in the UK.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24284038", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND: 4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954380", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 216, "text": "Bexsero is the first meningococcal B vaccine to be approved in the European Union. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25325113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Quantification by LC-MS(E) of outer membrane vesicle proteins of the Bexsero\u00ae vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24462403", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "We previously demonstrated the immunogenicity and tolerability of the serogroup B meningococcal vaccine, 4CMenB (Bexsero), in 11-17 y-olds randomized to receive 1, 2, or 3 doses at 1, 2, or 6 mo intervals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23811804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "This policy statement provides recommendations for the prevention of serogroup B meningococcal disease through the use of 2 newly licensed serogroup B meningococcal vaccines: MenB-FHbp (Trumenba; Wyeth Pharmaceuticals, a subsidiary of Pfizer, Philadelphia, PA) and MenB-4C (Bexsero; Novartis Vaccines, Siena, Italy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "An outbreak of Neisseria meningitidis serotype B infection occurred at a small residential university; public health announced an organizational vaccination program with the 4-component Meningococcal B (4CMenB) vaccine (Bexsero(TM), Novartis/GlaxoSmithKline Inc.) several days later.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27302338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Recently approved in the EU, US, Australia, and Canada, 4CMenB (Bexsero(\u00ae), GSK Vaccines) is a multi-component meningococcal B (MenB) vaccine containing 3 surface exposed recombinant proteins (fHbp, NadA, and NHBA) and New Zealand strain outer membrane vesicles (NZ OMV) containing PorA 1.4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25882169", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 257, "text": "In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109566", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 488, "text": "To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(\u00ae) against MenB disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109566", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 955, "text": "This has resulted in a multicomponent, recombinant, meningococcal serogroup B vaccine: 4CMenB (Bexsero(\u00ae), Novartis Vaccines & Diagnostics, NC, USA), containing four main immunogenic components: two recombinant fusion proteins (Neisseria heparin-binding antigen-GNA1030 and factor H-binding protein-GNA2091); recombinant Neisserial adhesion A; and detergent-treated outer membrane vesicles derived from the meningococcal NZ98/254 strain, where porin A 1.4 is the major immunodominant antigen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24815780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "BACKGROUND: 4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954380", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 298, "text": "In January 2015, FDA licensed a second MenB vaccine (MenB-4C [Bexsero, Novartis Vaccines]) as a 2-dose series.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26068564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Bexsero, a new vaccine against Neisseria meningitidis serogroup B (MenB), is composed of 3 main recombinant proteins and an outer membrane vesicle component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25713028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using a recently-licensed, multi-component, protein-based vaccine (Bexsero(\u00ae)).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25043395", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "[Bexsero, a novel vaccine against meningococcus].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26853725", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Modelling the cost-effectiveness of catch-up 'MenB' (Bexsero) vaccination in England.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27923519", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Re-evaluating cost effectiveness of universal meningitis vaccination (Bexsero) in England: modelling study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25301037", "endSection": "title" }, { "offsetInBeginSection": 476, "offsetInEndSection": 592, "text": "The novel vaccine Bexsero (previously 4CMenB) has been developed and proven safe and immunogenic in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero(\u00ae)): a review of its use in primary and booster vaccination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23575646", "endSection": "title" }, { "offsetInBeginSection": 53, "offsetInEndSection": 157, "text": "Bexsero, the recently licensed multicomponent vaccine against serogroup B Neisseria meningitidis (MenB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26304221", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 342, "text": "Recommendation for anti-meningococcal vaccination among these workers has been recently updated upon the licensure in Europe of Bexsero\u00ae vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27808594", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 894, "text": "Clinical recommendations for the use of Bexsero have been published in several countries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26686570", "endSection": "abstract" } ] }, { "body": "Is there a role for gamma knife in treatment of Obsessive-Compulsive Disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7841817", "http://www.ncbi.nlm.nih.gov/pubmed/8517190", "http://www.ncbi.nlm.nih.gov/pubmed/18188146", "http://www.ncbi.nlm.nih.gov/pubmed/25165567", "http://www.ncbi.nlm.nih.gov/pubmed/21150752", "http://www.ncbi.nlm.nih.gov/pubmed/24093580", "http://www.ncbi.nlm.nih.gov/pubmed/12856488", "http://www.ncbi.nlm.nih.gov/pubmed/24099662", "http://www.ncbi.nlm.nih.gov/pubmed/18081480", "http://www.ncbi.nlm.nih.gov/pubmed/25050687", "http://www.ncbi.nlm.nih.gov/pubmed/10099102", "http://www.ncbi.nlm.nih.gov/pubmed/23872618", "http://www.ncbi.nlm.nih.gov/pubmed/23829816", "http://www.ncbi.nlm.nih.gov/pubmed/19996247", "http://www.ncbi.nlm.nih.gov/pubmed/15554782", "http://www.ncbi.nlm.nih.gov/pubmed/18835422", "http://www.ncbi.nlm.nih.gov/pubmed/10069581", "http://www.ncbi.nlm.nih.gov/pubmed/25054836", "http://www.ncbi.nlm.nih.gov/pubmed/27903196" ], "ideal_answer": [ "Yes. Gamma knife radiosurgery is being increasingly to treat refractory obsessive- compulsive disorder (OCD). It is reserved for severe, treatment-refractory disease that has not responded to multiple treatments." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10933", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009771" ], "type": "yesno", "id": "5898500478275d0c4a000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "OBJECTIVE Functional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27903196", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1165, "text": "METHODS The authors constructed a linear-quadratic model of BED in functional GKRS with a dose-protraction factor to correct for intrafraction DNA-damage repair and used standard single-fraction doses for trigeminal nerve ablation for TN (85 Gy), thalamotomy for tremor (130 Gy), and capsulotomy for obsessive-compulsive disorder (180 Gy). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27903196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Gamma knife for obsessive compulsive disorder: can it be detrimental?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050687", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 318, "text": "Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050687", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1344, "text": "Radio and neurosurgical procedures, including gamma knife radiation and deep brain stimulation, are reserved for severe, treatment-refractory disease that has not responded to multiple treatments, and some patients may benefit from transcranial magnetic stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25165567", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1000, "text": " We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24099662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150752", "endSection": "title" }, { "offsetInBeginSection": 203, "offsetInEndSection": 316, "text": "Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10069581", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19996247", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: a structural MRI pilot prospective study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18835422", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150752", "endSection": "title" }, { "offsetInBeginSection": 1334, "offsetInEndSection": 1553, "text": "At 28 months, the third patient is living and working independently, and her YBOCS score is 18.CONCLUSION: Within a strict protocol, gamma knife radiosurgery provided improvement of OCD behavior with no adverse effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Gamma knife for obsessive compulsive disorder: can it be detrimental?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050687", "endSection": "title" } ] }, { "body": "What is the mechanism of action of the biguanide class of diabetes drugs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23292513", "http://www.ncbi.nlm.nih.gov/pubmed/27939359", "http://www.ncbi.nlm.nih.gov/pubmed/8914439", "http://www.ncbi.nlm.nih.gov/pubmed/25793062", "http://www.ncbi.nlm.nih.gov/pubmed/21147283", "http://www.ncbi.nlm.nih.gov/pubmed/26166607" ], "ideal_answer": [ "this biguanide is an oral insulin-sensitizing agent capable of increasing insulin sensitivity and decreasing plasma fasting insulin levels.", "Bioguaides like Metformin, decrease amount of glucose released from liver and increases insulin sensitivity. " ], "concepts": [ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275167", "http://www.disease-ontology.org/api/metadata/DOID:9351", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001645", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.biosemantics.org/jochem#4275167", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008687" ], "type": "summary", "id": "58a22eb460087bc10a000001", "snippets": [ { "offsetInBeginSection": 753, "offsetInEndSection": 792, "text": "Metformin sensitizes the insulin action", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939359", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 611, "text": "This biguanide is an oral insulin-sensitizing agent capable of increasing insulin sensitivity and decreasing plasma fasting insulin levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26166607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Metformin is an oral anti-diabetic drug of the biguanide class that is commonly used to treat type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21147283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Metformin, an oral anti-diabetic agent in the biguanide class is a widely prescribed drug to treat high blood glucose in patients with type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793062", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 401, "text": "etformin has three different roles, including blood glucose regulatory effect, protection of kidney tubular cell by acting as an effective antioxidant and finally ameliorative effect on diabetic kidney disease through saving the podocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793062", "endSection": "abstract" } ] }, { "body": "Where is the proteasome located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9799224", "http://www.ncbi.nlm.nih.gov/pubmed/26743630", "http://www.ncbi.nlm.nih.gov/pubmed/17428875", "http://www.ncbi.nlm.nih.gov/pubmed/9321388", "http://www.ncbi.nlm.nih.gov/pubmed/16371511", "http://www.ncbi.nlm.nih.gov/pubmed/15791592", "http://www.ncbi.nlm.nih.gov/pubmed/11734567", "http://www.ncbi.nlm.nih.gov/pubmed/11295498", "http://www.ncbi.nlm.nih.gov/pubmed/7957966", "http://www.ncbi.nlm.nih.gov/pubmed/22411744", "http://www.ncbi.nlm.nih.gov/pubmed/10995887", "http://www.ncbi.nlm.nih.gov/pubmed/20026058", "http://www.ncbi.nlm.nih.gov/pubmed/18948196", "http://www.ncbi.nlm.nih.gov/pubmed/10502681", "http://www.ncbi.nlm.nih.gov/pubmed/20491623", "http://www.ncbi.nlm.nih.gov/pubmed/9050876", "http://www.ncbi.nlm.nih.gov/pubmed/21976669", "http://www.ncbi.nlm.nih.gov/pubmed/17977463", "http://www.ncbi.nlm.nih.gov/pubmed/25413350", "http://www.ncbi.nlm.nih.gov/pubmed/22458048", "http://www.ncbi.nlm.nih.gov/pubmed/11175258", "http://www.ncbi.nlm.nih.gov/pubmed/9804081", "http://www.ncbi.nlm.nih.gov/pubmed/10657252" ], "ideal_answer": [ "The proteasome can be found in perinuclear and nuclear location, as well as in cytosolic compartments, such as mitochondria and endoplasmic reticulum. Proteasome-mediated degradation of cell cycle regulatory proteins, production and loading of antigenic peptides onto HLA molecules, and transient homing of diverse virion proteins required for entry and/or egress have been also shown to be coordinated at the centrosome." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0000502", "http://amigo.geneontology.org/amigo/term/GO:0031144" ], "type": "summary", "id": "58b558d522d3005309000006", "snippets": [ { "offsetInBeginSection": 409, "offsetInEndSection": 611, "text": "Cellular regulation by UPS- mediated protein degradation is a highly specific and selective process that depends on time (e.g. cell cycle) and location (nucleus, mitochondria or endoplasmic reticulum). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26743630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "In eukaryotic cells, regulated protein degradation of intracellular proteins is mediated largely by the ubiquitin proteasome system (UPS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26743630", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 689, "text": "We followed two key parameters of this process: the distribution of proteasomes in nuclear and cytosolic compartments, and the formation of cytoplasmic aggregate-like structures called proteasome storage granules (PSGs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25413350", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 1042, "text": "Subsequently, cellular distribution of the PAI-2\u00b7proteasome complexes was established by immunogold staining and electron microscopy analyses. As judged by confocal microscopy, both proteins appeared in a diffuse cytosolic pattern, but they also could be found in a dense perinuclear and nuclear location. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21976669", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 302, "text": " Frequently ubiquitinated proteins are targeted to the proteasome for degradation in the cytosol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18948196", "endSection": "abstract" }, { "offsetInBeginSection": 1354, "offsetInEndSection": 1636, "text": " More recently, proteasome-mediated degradation of cell cycle regulatory proteins, production and loading of antigenic peptides onto HLA molecules, and transient homing of diverse virion proteins required for entry and/or egress have been shown to be coordinated at the centrosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17428875", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1363, "text": "We conclude that N-terminal sequences of Wld(S) protein influence the intranuclear location of both ubiquitin proteasome and NAD(+) synthesis machinery and that an evolutionary recent sequence mediates binding of mammalian Ube4b to VCP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16371511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Two new forms of proteasomes, designated as the endoplasmic reticulum (ER) membrane-associated proteasome (ERa proteasome) and ER membrane-bound proteasome (ERb proteasome), were purified to homogeneity from 0.0125 and 2.5% sodium cholate extracts, respectively, of a rat liver microsomal fraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502681", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 396, "text": "The proteasome is a large multicatalytic, proteinase complex located in the cytosol and the nucleus of eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22458048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9799224", "endSection": "title" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1500, "text": "JAB1, which is thought to bind p27KIP1 and transport it from the nucleus to the cytoplasm for proteasome/ubiquitin-mediated degradation, was found to be localized both in the cytoplasm and the nucleus in undifferentiated and differentiating tumors whereas located predominantly in the nucleus of differentiated tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10995887", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 896, "text": "20S proteasomes are present in all areas where ATPase subunits are detected, consistent with the presence of intact 26S proteasomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11175258", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1091, "text": "Inhibition of proteasomes located in axons resulted in an accumulation of ubiquitinated proteins in these axons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22411744", "endSection": "abstract" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1639, "text": "All these observations indicate that the mouse sperm proteasome participates in the binding to the zona pellucida and the acrosome reaction and that there is a pool of proteasomes located on the sperm head..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15791592", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1387, "text": "Thus, newly synthesized apoB is localized throughout the entire ER and degraded homogeneously, most likely by neighboring proteasomes located on the cytosolic side of the ER membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11734567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "While misfolded and short-lived proteins are degraded in proteasomes located in the nucleus and cytoplasm, the degradation of organelles and long-lived proteins in the lysosome occurs by the process of autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17977463", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 610, "text": "The GFP-tagged proteasomes were located within both the cytoplasm and the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9321388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Proteasomes are large multicatalytic proteinase complexes located in the cytosol and the nucleus of eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20491623", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 549, "text": "Immunohistochemically, proteasomes (26S) were located in the cytoplasm in normal human muscle, but the staining intensity was weak.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9804081", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 867, "text": "In DMRV, proteasomes often were located within or on the rim of rimmed vacuoles, and in the cytoplasm of atrophic fibers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9804081", "endSection": "abstract" } ] }, { "body": "What is clinical presentation of the Gardner-Diamond syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26078671", "http://www.ncbi.nlm.nih.gov/pubmed/15956886", "http://www.ncbi.nlm.nih.gov/pubmed/2345102", "http://www.ncbi.nlm.nih.gov/pubmed/12838436", "http://www.ncbi.nlm.nih.gov/pubmed/27011410", "http://www.ncbi.nlm.nih.gov/pubmed/23825859", "http://www.ncbi.nlm.nih.gov/pubmed/21548659", "http://www.ncbi.nlm.nih.gov/pubmed/4059144", "http://www.ncbi.nlm.nih.gov/pubmed/26137346", "http://www.ncbi.nlm.nih.gov/pubmed/23723552", "http://www.ncbi.nlm.nih.gov/pubmed/26101006", "http://www.ncbi.nlm.nih.gov/pubmed/19030312", "http://www.ncbi.nlm.nih.gov/pubmed/19192020", "http://www.ncbi.nlm.nih.gov/pubmed/18417404", "http://www.ncbi.nlm.nih.gov/pubmed/16023271", "http://www.ncbi.nlm.nih.gov/pubmed/23580908", "http://www.ncbi.nlm.nih.gov/pubmed/3627621", "http://www.ncbi.nlm.nih.gov/pubmed/20204908", "http://www.ncbi.nlm.nih.gov/pubmed/921453", "http://www.ncbi.nlm.nih.gov/pubmed/10966177", "http://www.ncbi.nlm.nih.gov/pubmed/11475645" ], "ideal_answer": [ "Psychogenic purpura, also known as Gardner-Diamond syndrome, is a rare, distinctive, localized cutaneous reaction pattern mostly affecting psychologically disturbed adult women. Repeated crops of tender, ill-defined ecchymotic lesions on the extremities and external bleeding from other sites characterize the condition." ], "type": "summary", "id": "5895e2567d9090f353000011", "snippets": [ { "offsetInBeginSection": 542, "offsetInEndSection": 771, "text": "Antidepressants were prescribed by the psychiatrist that not only cured the depression with time but also the bleeding episodes which were actually related to child's depression (Gardner-Diamond syndrome or psychogenic purpura). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26101006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Psychogenic Purpura (Gardner-Diamond Syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137346", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Psychogenic purpura, also known as Gardner-Diamond syndrome or autoerythrocyte sensitization syndrome, is a rare condition characterized by spontaneous development of painful edematous skin lesions progressing to ecchymosis over the next 24 hours. Severe stress and emotional trauma always precede the skin lesions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Gardner Diamond syndrome is a rare condition characterized with painful ecchymoses in different parts of the body and cutaneous and mucosal hemorrhages. The etiology is not known fully and psychogenic factors are thought to be involved. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26078671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Psychogenic purpura, also known as Gardner-Diamond syndrome, is a rare, distinctive, localized cutaneous reaction pattern mostly affecting psychologically disturbed adult women. Repeated crops of tender, ill-defined ecchymotic lesions on the extremities and external bleeding from other sites characterize the condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23825859", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 766, "text": "PPDDM includes impulse control disorders, obsessive-compulsive disorders, factitious disorder, factitious disorder by proxy, self-mutilation, delusions of parasitosis, psychogenic purpura/Gardner-Diamond syndrome, and cutaneous sensory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Psychogenic purpura (Gardner-Diamond syndrome) is the occurrence and spontaneous recurrence of painful ecchymosis following emotional stress and minor trauma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20204908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "We describe the clinical presentation and course of a patient with autoerythrocyte sensitization (Gardner-Diamond) syndrome, and review the literature for similar cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10966177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Gardner-Diamond syndrome (GDS) is also known as psychogenic purpura, autoerythrocyte sensitization syndrome and painful bruising syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Autoerythrocyte sensitization (Gardner-Diamond) syndrome mimicking compartment syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12838436", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome): review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19192020", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "We report a case with an unusual manifestation of autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12838436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The Gardner-Diamond syndrome is a disorder characterized by recurrent spontaneous painful bruising in patients with underlying psychosis and neurosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15956886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "A 54-year old anorectic patient with painful bruising syndrome (Gardner-Diamond syndrome) suffered from various gastrointestinal and psychologic complaints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11475645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "This paper presents a 26-year-old woman with the characteristic features of Gardner-Diamond syndrome: recurrent painful bruises reproducible by intradermal injection of autologous red blood cells, and a \"hysterical\" personality pattern together with nonspecific multisystem complaints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2345102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Gardner-Diamond's syndrome, or autoerythrocyte sensitization, is a disorder of spontaneous, painful ecchymoses whose pathogenesis is unresolved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/921453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Autoerythrocyte sensitization (Gardner-Diamond) syndrome mimicking compartment syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12838436", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Autoerythrocyte sensitization (Gardner-Diamond) syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10966177", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome) associated with cutaneous vasculitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18417404", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Gardner-Diamond syndrome (GDS) is an uncommon disease clinically characterized by a wide spectrum of psycho-emotive symptoms associated with painful ecchymoses/purpuric lesions and positivity of auto-erythrocyte sensitization skin test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27011410", "endSection": "abstract" } ] }, { "body": "Where can you find the annulus of Zinn?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24697862", "http://www.ncbi.nlm.nih.gov/pubmed/17080461", "http://www.ncbi.nlm.nih.gov/pubmed/9783284", "http://www.ncbi.nlm.nih.gov/pubmed/22336122", "http://www.ncbi.nlm.nih.gov/pubmed/25744329", "http://www.ncbi.nlm.nih.gov/pubmed/16917665", "http://www.ncbi.nlm.nih.gov/pubmed/16955671", "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "http://www.ncbi.nlm.nih.gov/pubmed/11601571", "http://www.ncbi.nlm.nih.gov/pubmed/25650797", "http://www.ncbi.nlm.nih.gov/pubmed/21772799", "http://www.ncbi.nlm.nih.gov/pubmed/8604741", "http://www.ncbi.nlm.nih.gov/pubmed/17667093", "http://www.ncbi.nlm.nih.gov/pubmed/8827557" ], "ideal_answer": [ "Annulus of Zinn is in the orbit." ], "exact_answer": [ "orbit", "EYE" ], "type": "factoid", "id": "58917c88621ea6ff7e00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Should the annular tendon of the eye be named 'annulus of Zinn' or 'of Valsalva'?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24697862", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "The annular tendon is commonly named 'annulus of Zinn', from the German anatomist and botanist Johann Gottfried Zinn (1727-1759) who described this structure in his Descriptio anatomica oculi humani (Anatomical Description of the Human Eye, 1755).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24697862", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 683, "text": "It arose at the annulus of Zinn, passing forwards between the inferior rectus muscle and lateral rectus muscle, and insert directly on the sclera. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22336122", "endSection": "abstract" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1133, "text": "Drilling was continued toward the annulus of Zinn (AZ) and optic nerve superiorly and over the intracavernous ICA posteriorly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21772799", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 811, "text": "Measurements before and after resection of the ACP included the length of C6 segment of the ICA on its lateral aspect; C6 segment length on its medial aspect; and medial length of the optic nerve from the optic chiasm to falciform ligament (before ACP resection) then to the annulus of Zinn (after ACP resection).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16917665", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 499, "text": "The muscles, situated between the optic nerve and the lateral rectus muscle, originated from the annulus of Zinn and branched off two heads; one inserted into the medial inferior side of the superior rectus muscle and the other inserted into the central superior side of the inferior rectus muscle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16955671", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 603, "text": " In 30 cadavers, the superior division of the oculomotor nerve was severed en bloc 1.5 cm anterior to the annulus of Zinn with the levator palpebrae superioris (LPS) and the superior rectus muscles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11601571", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 474, "text": "The optic canal was subsequently removed en bloc, beginning at the annulus of Zinn and extending to the optic chiasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17667093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 609, "text": "PURPOSE: To describe a combined transcranial-orbital approach for en bloc resection of optic nerve gliomas with preservation of the annulus of Zinn that minimizes recurrence and prevents postoperative paralytic ptosis.DESIGN: A retrospective, noncomparative, interventional case series.STUDY POPULATION: All patients who underwent optic nerve glioma resections using this technique with the authors between 1994 and 2010.PROCEDURE: A transcranial-orbital approach is used to resect the intracranial segment of the optic nerve glioma from 2 mm anterior to the chiasm to the posterior extent of annulus of Zinn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1565, "text": "No patients had tumor recurrence or developed postoperative paralytic ptosis.CONCLUSIONS: The combined transcranial-orbital approach with preservation of the annulus of Zinn is a safe and effective way to remove optic nerve gliomas and ensure tumor clearance while avoiding paralytic ptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 562, "text": "To describe a combined transcranial-orbital approach for en bloc resection of optic nerve gliomas with preservation of the annulus of Zinn that minimizes recurrence and prevents postoperative paralytic ptosis.A retrospective, noncomparative, interventional case series.All patients who underwent optic nerve glioma resections using this technique with the authors between 1994 and 2010.A transcranial-orbital approach is used to resect the intracranial segment of the optic nerve glioma from 2 mm anterior to the chiasm to the posterior extent of annulus of Zinn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 798, "text": "Through a superior orbitotomy exposure, the entire retrobulbar segment of the tumor is transected from the globe to the annulus of Zinn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 1194, "text": "A simulation of the procedure in a cadaver and en bloc resection of the orbital apex are performed to demonstrate the subdural plane of dissection within the annulus of Zinn.Postoperative outcome measures include: health of the ipsilateral globe, paralytic ptosis, postoperative complications, and tumor recurrence.Eleven patients underwent resection of optic nerve gliomas using this technique", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "endSection": "abstract" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1473, "text": "No patients had tumor recurrence or developed postoperative paralytic ptosis.The combined transcranial-orbital approach with preservation of the annulus of Zinn is a safe and effective way to remove optic nerve gliomas and ensure tumor clearance while avoiding paralytic ptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 575, "text": "The orbital surface of the medial rectus and inferior rectus are exposed from the annulus of Zinn to a position close to where the muscles penetrate Tenons capsule", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8827557", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 579, "text": "The orbital surface of the medial rectus and inferior rectus are exposed from the annulus of Zinn to a position close to where the muscles penetrate Tenon's capsule. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8827557", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 498, "text": "The muscles, situated between the optic nerve and the lateral rectus muscle, originated from the annulus of Zinn and branched off two heads; one inserted into the medial inferior side of the superior rectus muscle and the other inserted into the central superior side of the inferior rectus muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16955671", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 456, "text": "The optic canal was subsequently removed en bloc, beginning at the annulus of Zinn and extending to the optic chiasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17667093", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1114, "text": "The distance from the annulus of Zinn to the trochlea was the same in both eyes.The findings for our patients, particularly in those who underwent additional high resolution MRI, did not provide evidence of a lack of CN IV as a cause of Brown syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25744329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Should the annular tendon of the eye be named 'annulus of Zinn' or 'of Valsalva'?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24697862", "endSection": "title" }, { "offsetInBeginSection": 864, "offsetInEndSection": 944, "text": "The distance from the annulus of Zinn to the trochlea was the same in both eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25744329", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 457, "text": "The optic canal was subsequently removed en bloc, beginning at the annulus of Zinn and extending to the optic chiasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17667093", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 802, "text": "Through a superior orbitotomy exposure, the entire retrobulbar segment of the tumor is transected from the globe to the annulus of Zinn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581081", "endSection": "abstract" } ] }, { "body": "What is the indication for SLCO1B1 genotyping?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26131212", "http://www.ncbi.nlm.nih.gov/pubmed/27595674", "http://www.ncbi.nlm.nih.gov/pubmed/25181036", "http://www.ncbi.nlm.nih.gov/pubmed/25150868", "http://www.ncbi.nlm.nih.gov/pubmed/25563221" ], "ideal_answer": [ "HMG Co-A reductase inhibitors, commonly known as statins, also display wide interindividual variability in plasma concentration, response and toxicity due in part to polymorphisms in transporter genes, including SLCO1B1 and ABCG2. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin." ], "exact_answer": [ "Statin treatment" ], "type": "factoid", "id": "58bbc0fc22d300530900001c", "snippets": [ { "offsetInBeginSection": 264, "offsetInEndSection": 509, "text": "including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27595674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27595674", "endSection": "title" }, { "offsetInBeginSection": 1834, "offsetInEndSection": 2075, "text": "Similarly, HMG Co-A reductase inhibitors, commonly known as statins, also display wide interindividual variability in plasma concentration, response and toxicity due in part to polymorphisms in transporter genes, including SLCO1B1 and ABCG2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25181036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Association of SLCO1B1 gene polymorphisms with toxicity response of high dose methotrexate chemotherapy in childhood acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26131212", "endSection": "title" }, { "offsetInBeginSection": 610, "offsetInEndSection": 775, "text": " development of SLCO1B1 genotyping to avoid statin induced adverse drug reactions is discussed as a model case for transporter pharmacogenetics clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25150868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The effects of SLCO1B1*5 genotype guided statin therapy (GGST) are unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25563221", "endSection": "abstract" } ] }, { "body": "List available circular RNA prediction tools.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26657634" ], "ideal_answer": [ "circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice." ], "exact_answer": [ [ "circRNA_finder" ], [ "find_circ" ], [ "CIRCexplorer" ], [ "CIRI" ], [ "MapSplice" ] ], "type": "list", "id": "588f220e3b87a8a73800000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1119, "text": "CircRNAs are novel members of the non-coding RNA family. For several decades circRNAs have been known to exist, however only recently the widespread abundance has become appreciated. Annotation of circRNAs depends on sequencing reads spanning the backsplice junction and therefore map as non-linear reads in the genome. Several pipelines have been developed to specifically identify these non-linear reads and consequently predict the landscape of circRNAs based on deep sequencing datasets. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. By this approach, we observe surprisingly dramatic differences between the algorithms specifically regarding the highly expressed circRNAs and the circRNAs derived from proximal splice sites. Collectively, this study emphasizes that circRNA annotation should be handled with care and that several algorithms should ideally be combined to achieve reliable predictions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26657634", "endSection": "abstract" } ] }, { "body": "Which disease is treated with Nusinersen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26823478", "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "http://www.ncbi.nlm.nih.gov/pubmed/26865511" ], "ideal_answer": [ "Nusinersen us used for treatment of Spinal Muscular Atrophy." ], "exact_answer": [ "Spinal Muscular Atrophy", "SMA" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category" ], "type": "factoid", "id": "589185cc621ea6ff7e00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26823478", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26823478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 465, "text": "OBJECTIVE: To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMNRx), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA).METHODS: Nusinersen was delivered by intrathecal injection to medically stable patients with type 2 and type 3 SMA aged 2-14 years in an open-label phase 1 study and its long-term extension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1695, "text": "CONCLUSIONS: Results from this study support continued development of nusinersen for treatment of SMA.CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in children with SMA, intrathecal nusinersen is not associated with safety or tolerability concerns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 626, "text": "BACKGROUND: Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy. Nusinersen is specifically designed to alter splicing of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron (SMN) protein that is deficient in patients with spinal muscular atrophy.METHODS: This open-label, phase 2, escalating dose clinical study assessed the safety and tolerability, pharmacokinetics, and clinical efficacy of multiple intrathecal doses of nusinersen (6 mg and 12 mg dose equivalents) in patients with infantile-onset spinal muscular atrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "abstract" }, { "offsetInBeginSection": 3149, "offsetInEndSection": 3289, "text": "Results informed the design of an ongoing, sham-controlled, phase 3 clinical study of nusinersen in infantile-onset spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26823478", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 283, "text": "We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26823478", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 333, "text": "Nusinersen is specifically designed to alter splicing of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron (SMN) protein that is deficient in patients with spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMNRx), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26823478", "endSection": "title" }, { "offsetInBeginSection": 1396, "offsetInEndSection": 1485, "text": "Results from this study support continued development of nusinersen for treatment of SMA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "title" }, { "offsetInBeginSection": 3105, "offsetInEndSection": 3245, "text": "Results informed the design of an ongoing, sham-controlled, phase 3 clinical study of nusinersen in infantile-onset spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "abstract" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 1630, "text": "This study provides Class IV evidence that in children with SMA, intrathecal nusinersen is not associated with safety or tolerability concerns..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 284, "text": "We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26823478", "endSection": "abstract" } ] }, { "body": "Which disease the London mutation involved in?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17431643", "http://www.ncbi.nlm.nih.gov/pubmed/20409323", "http://www.ncbi.nlm.nih.gov/pubmed/10525535", "http://www.ncbi.nlm.nih.gov/pubmed/16426772", "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "http://www.ncbi.nlm.nih.gov/pubmed/15380017", "http://www.ncbi.nlm.nih.gov/pubmed/24145776", "http://www.ncbi.nlm.nih.gov/pubmed/27421117", "http://www.ncbi.nlm.nih.gov/pubmed/21389247", "http://www.ncbi.nlm.nih.gov/pubmed/22171952", "http://www.ncbi.nlm.nih.gov/pubmed/16467370", "http://www.ncbi.nlm.nih.gov/pubmed/24524897", "http://www.ncbi.nlm.nih.gov/pubmed/17215062", "http://www.ncbi.nlm.nih.gov/pubmed/15197738", "http://www.ncbi.nlm.nih.gov/pubmed/23747045", "http://www.ncbi.nlm.nih.gov/pubmed/15314265", "http://www.ncbi.nlm.nih.gov/pubmed/19771217", "http://www.ncbi.nlm.nih.gov/pubmed/25108425", "http://www.ncbi.nlm.nih.gov/pubmed/20025930", "http://www.ncbi.nlm.nih.gov/pubmed/10500121" ], "ideal_answer": [ "London mutation that is the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile) is involved in Alzheimer's Disease." ], "exact_answer": [ "Alzheimer's Disease", "AD" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017354", "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020125", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016564", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194" ], "type": "factoid", "id": "58b6978822d300530900000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22171952", "endSection": "abstract" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1092, "text": "The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22171952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 856, "text": "One major hallmark of Alzheimer's disease (AD) is the massive loss of synapses that occurs at an early clinical stage of the disease. In this study, we characterize alterations in spine density and the expression of synapse-associated immediate early gene Arc (activity-regulated cytoskeleton-associated protein) in the hippocampal CA1 regions of two different amyloid precursor protein (APP) transgenic mouse lines before plaque development and their connection to performance in hippocampus-dependent memory tests. The density of mushroom-type spines was reduced by 34% in the basal dendrites proximal to the soma of CA1 pyramidal neurons in 5.5-month-old Tg2576 mice, carrying the Swedish mutation, compared with wild-type littermates. A similar reduction of 42% was confirmed in the same region of 8-month-old APP/Lo mice, carrying the London mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21389247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "endSection": "title" }, { "offsetInBeginSection": 145, "offsetInEndSection": 310, "text": "We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 579, "text": "In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far. Two subjects of the other family with AD diagnosis were carriers of the same mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 628, "text": "A pathological hallmark in the brain of an AD patient is extracellular amyloid plaques formed by accumulated beta-amyloid protein (Abeta), a metabolic product of amyloid precursor protein (APP). Studies have revealed a strong genetic linkage in the early-onset familial form (<60 years old) of AD. For example, some mutant APPs are transmitted dominantly and are segregated with inheritance of early onset AD. These mutants facilitate Abeta production. The \"Swedish\" mutations (APP(SW)) and the \"London\" mutation (APP(LON)) are examples of these mutants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426772", "endSection": "abstract" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1487, "text": "The sequences that are effective to silence APP(SW) and APP(LON) as identified in this study may be useful in both in vivo and in vitro studies to investigate the pathophysiological role of APP(SW) and APP(LON) in AD development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426772", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 638, "text": "Here, we show ASP-RNAi against the Swedish- and London-type amyloid precursor protein (APP) variants related to familial Alzheimer's disease using two reporter alleles encoding the Photinus and Renilla luciferase genes and carrying mutant and wild-type allelic sequences in their 3'-untranslated regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19771217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Transgenic mice over-expressing a mutated form of the human amyloid precursor protein (APP, 695 isoform) bearing a mutation associated with Alzheimer's disease (V642I, so-called London mutation, hereafter APPLd2) and wild-type controls were studied at age periods (3 and 10 months) prior to the overt development of neuritic amyloid plaques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15380017", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 622, "text": "The \"Swedish\" mutations (APP(SW)) and the \"London\" mutation (APP(LON)) are examples of these mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Allele-specific silencing of Alzheimer's disease genes: the amyloid precursor protein genes with Swedish or London mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426772", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 455, "text": "Mutations in the amyloid precursor protein gene were the first to be recognized as a cause of Alzheimers disease (AD).We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation.In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimers disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "endSection": "title" }, { "offsetInBeginSection": 415, "offsetInEndSection": 584, "text": "We analyzed the cytotoxic mechanisms of the London-type AbetaPP mutant, V642I-AbetaPP, in primary cortical neurons utilizing an adenovirus-mediated gene transfer system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15197738", "endSection": "abstract" }, { "offsetInBeginSection": 1806, "offsetInEndSection": 2003, "text": "We demonstrate that the APP-London and PS1 mutations have additive effects on the increased secretion of betaA4(1-42) relative to betaA4(1-40), indicating that both mutations operate independently.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10525535", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1323, "text": "Pathogenic mutations in APP at codon 717 (APP \"London\") lead to an increased proportion of Abeta 1-42 being produced and secreted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10500121", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 627, "text": "The \"Swedish\" mutations (APP(SW)) and the \"London\" mutation (APP(LON)) are examples of these mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Allele-specific silencing of Alzheimer's disease genes: the amyloid precursor protein genes with Swedish or London mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426772", "endSection": "title" }, { "offsetInBeginSection": 120, "offsetInEndSection": 285, "text": "We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20523046", "endSection": "title" }, { "offsetInBeginSection": 246, "offsetInEndSection": 341, "text": "Such cleavage is promoted by the Swedish and London mutations (APPSwe/Lon) inside the APP gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20025930", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1121, "text": "We also show that the Swedish and London mutations reduce the amount of APP in the lysosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20409323", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1479, "text": "This rapid transit to the lysosome is blocked by the presence of either the London or Swedish mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20409323", "endSection": "abstract" } ] }, { "body": "Define lncRNA.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26207516", "http://www.ncbi.nlm.nih.gov/pubmed/26166759", "http://www.ncbi.nlm.nih.gov/pubmed/25994219", "http://www.ncbi.nlm.nih.gov/pubmed/26004516", "http://www.ncbi.nlm.nih.gov/pubmed/26142536", "http://www.ncbi.nlm.nih.gov/pubmed/27729273" ], "ideal_answer": [ "Long noncoding RNAs (lncRNAs) represent a newly discovered class of regulatory molecules that impact a variety of biological processes in cells and organ systems. In humans, it is estimated that there may be more than twice as many lncRNA genes than protein-coding genes. However, only a handful of lncRNAs have been analyzed in detail.\nLong non-coding RNAs (lncRNAs) are emerging as key molecules in cancers, yet their potential molecular mechanisms are not well understood.\nlong noncoding RNAs (lncRNAs), the largest family of noncoding transcripts, have emerged as common regulators of many cellular stressors; including heat shock, metabolic deprivation and DNA damage." ], "type": "summary", "id": "58bc696b02b8c60953000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Protein-coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26207516", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 336, "text": "Recently, aberrant expression of long noncoding RNAs (lncRNAs) has been considered as a primary feature of many types of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Long noncoding RNAs (lncRNAs) represent a newly discovered class of regulatory molecules that impact a variety of biological processes in cells and organ systems. In humans, it is estimated that there may be more than twice as many lncRNA genes than protein-coding genes. However, only a handful of lncRNAs have been analyzed in detail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26166759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Genomic imprinting has been a great resource for studying transcriptional and post-transcriptional-based gene regulation by long noncoding RNAs (lncRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26004516", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 150, "text": "Long non-coding RNAs (lncRNAs) are emerging as key molecules in cancers, yet their potential molecular mechanisms are not well understood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25994219", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 904, "text": "long noncoding RNAs (lncRNAs), the largest family of noncoding transcripts, have emerged as common regulators of many cellular stressors; including heat shock, metabolic deprivation and DNA damage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26142536", "endSection": "abstract" } ] }, { "body": "How many microorganisms are present in human normal gut?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26613639", "http://www.ncbi.nlm.nih.gov/pubmed/26908163", "http://www.ncbi.nlm.nih.gov/pubmed/26627987", "http://www.ncbi.nlm.nih.gov/pubmed/26945826" ], "ideal_answer": [ "Human gut microbiota is home to 10 to 100 trillions microorganisms." ], "exact_answer": [ "10 to 100 trillions microorganisms." ], "type": "factoid", "id": "58bc347422d300530900001e", "snippets": [ { "offsetInBeginSection": 267, "offsetInEndSection": 494, "text": ". A major breakthrough in understanding the etiology of neurological disorders is the recent insight on the role of the gut microbiota (GM). Human GM also referred to as the \"forgotten organ\" is home to 10(13-14) microorganisms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26613639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The gut microbiome comprises the collective genome of the trillions of microorganisms residing in our gastrointestinal ecosystem.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26627987", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 847, "text": "The gut microbiome (i.e. the 100 trillion symbiotic microorganisms which inhabit the mammalian gastrointestinal tract) influences numerous aspects of host metabolism, development and immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26908163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The microorganisms inhabiting the human gut are abundant (10(14) cells) and diverse (approximately 500 species per individual).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26945826", "endSection": "abstract" } ] }, { "body": "What is the role of 3,4-diaminobenzoic acid derivatives in the immune system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25635706" ], "ideal_answer": [ "3,4-diaminobenzoic acid derivatives are inhibitors of the oxytocinase subfamily of M1 aminopeptidases with immune-regulating properties. Cell-based analysis indicated that the lead compounds can be effective in downregulating macrophage activation induced by lipopolysaccharide and interferon-\u03b3 as well as cross-presentation by bone marrow-derived dendritic cells." ], "exact_answer": [ "Inhibition of the oxytocinase subfamily of M1 aminopeptidases with immune-regulating properties." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007154", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4258378", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007107", "http://www.biosemantics.org/jochem#4258378" ], "type": "factoid", "id": "5887fe7d3b87a8a738000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "3,4-diaminobenzoic acid derivatives as inhibitors of the oxytocinase subfamily of M1 aminopeptidases with immune-regulating properties.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635706", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1029, "text": "Members of the oxytocinase subfamily of M1 aminopeptidases (ERAP1, ERAP2, and IRAP) play important roles in both the adaptive and innate human immune responses. Their enzymatic activity can contribute to the pathogenesis of several major human diseases ranging from viral and parasitic infections to autoimmunity and cancer. We have previously demonstrated that diaminobenzoic acid derivatives show promise as selective inhibitors for this group of aminopeptidases. In this study, we have thoroughly explored a series of 3,4-diaminobenzoic acid derivatives as inhibitors of this class of enzymes, achieving submicromolar inhibitors for ERAP2 (IC50 = 237 nM) and IRAP (IC50 = 105 nM). Cell-based analysis indicated that the lead compounds can be effective in downregulating macrophage activation induced by lipopolysaccharide and interferon-\u03b3 as well as cross-presentation by bone marrow-derived dendritic cells. Our results indicate that this class of inhibitors may be useful for the targeted downregulation of immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "3,4-diaminobenzoic acid derivatives as inhibitors of the oxytocinase subfamily of M1 aminopeptidases with immune-regulating properties", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635706", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Members of the oxytocinase subfamily of M1 aminopeptidases (ERAP1, ERAP2, and IRAP) play important roles in both the adaptive and innate human immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "3,4-diaminobenzoic acid derivatives as inhibitors of the oxytocinase subfamily of M1 aminopeptidases with immune-regulating properties.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635706", "endSection": "title" } ] }, { "body": "Can NADPH oxidase be inhibited by apocynin and diphenylene iodonium?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22503982", "http://www.ncbi.nlm.nih.gov/pubmed/26728380", "http://www.ncbi.nlm.nih.gov/pubmed/17962358", "http://www.ncbi.nlm.nih.gov/pubmed/17046555", "http://www.ncbi.nlm.nih.gov/pubmed/19819434", "http://www.ncbi.nlm.nih.gov/pubmed/1324836", "http://www.ncbi.nlm.nih.gov/pubmed/15271858", "http://www.ncbi.nlm.nih.gov/pubmed/12424096", "http://www.ncbi.nlm.nih.gov/pubmed/16393992", "http://www.ncbi.nlm.nih.gov/pubmed/15308331", "http://www.ncbi.nlm.nih.gov/pubmed/25920934", "http://www.ncbi.nlm.nih.gov/pubmed/18195159", "http://www.ncbi.nlm.nih.gov/pubmed/24794531", "http://www.ncbi.nlm.nih.gov/pubmed/21693104", "http://www.ncbi.nlm.nih.gov/pubmed/24037962", "http://www.ncbi.nlm.nih.gov/pubmed/22134950", "http://www.ncbi.nlm.nih.gov/pubmed/11755128", "http://www.ncbi.nlm.nih.gov/pubmed/20698853", "http://www.ncbi.nlm.nih.gov/pubmed/16741139", "http://www.ncbi.nlm.nih.gov/pubmed/17341601", "http://www.ncbi.nlm.nih.gov/pubmed/19892012", "http://www.ncbi.nlm.nih.gov/pubmed/15845907", "http://www.ncbi.nlm.nih.gov/pubmed/3800872", "http://www.ncbi.nlm.nih.gov/pubmed/17662968", "http://www.ncbi.nlm.nih.gov/pubmed/17904225", "http://www.ncbi.nlm.nih.gov/pubmed/23229789", "http://www.ncbi.nlm.nih.gov/pubmed/21159852", "http://www.ncbi.nlm.nih.gov/pubmed/12867501", "http://www.ncbi.nlm.nih.gov/pubmed/19281832", "http://www.ncbi.nlm.nih.gov/pubmed/2121828", "http://www.ncbi.nlm.nih.gov/pubmed/15346654", "http://www.ncbi.nlm.nih.gov/pubmed/25666589", "http://www.ncbi.nlm.nih.gov/pubmed/20860666" ], "ideal_answer": [ "Yes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can be inhibited by apocynin or diphenylene iodonium (DPI)." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016174", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4251947", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019255", "http://www.biosemantics.org/jochem#4270191", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4276074", "http://amigo.geneontology.org/amigo/term/GO:0043020" ], "type": "yesno", "id": "58a5924060087bc10a000020", "snippets": [ { "offsetInBeginSection": 637, "offsetInEndSection": 968, "text": "Ang II treatment also led to a significant increment in intracellular reactive oxygen species generation, which could be fully abolished by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors apocynin or diphenylene iodonium, indicating that Ang II enhanced oxidative stress via a NADPH oxidase-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25666589", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1390, "text": "NOX inhibitors (diphenylene iodonium (DPI) or apocynin) were able to achieve similar results to that of ML-7 except no effect on MLCK activity and MLC20 phosphorylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25920934", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1375, "text": "Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24037962", "endSection": "abstract" }, { "offsetInBeginSection": 930, "offsetInEndSection": 1216, "text": "Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794531", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 820, "text": "Remarkably, Ang-II induced reactive oxygen species (ROS) via a NAD(P)H oxidase-dependent mechanism, as shown by inhibition of ROS production via the NAD(P)H oxidase inhibitors diphenylene iodonium (DPI) and apocynin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21693104", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1194, "text": "Moreover, NADPH oxidase activation by beta CD (145.5+/-9.0%; control: 98.6+/-1.6%) was also abrogated by the NADPH oxidase inhibitors apocynin (100.4+/-3.2%) and diphenylene iodonium (9.5+/-3.3%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18195159", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 870, "text": "We used structurally diverse NADPH oxidase inhibitors, aminoethyl-benzenesulfonylfluoride (AEBSF, 100-1000microM), apocynin (100-1000microM), and diphenylene iodonium (DPI, 3-30microM), to inhibit intrinsic NADPH oxidase activity in N27 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17904225", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1149, "text": "Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662968", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 453, "text": "With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12424096", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1057, "text": "The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341601", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 732, "text": "The effects of diphenylene iodonium (DPI) and apocynin, inhibitors of NADPH oxidase, on key parameters of PSC activation were evaluated in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962358", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1250, "text": "These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oA\u00e2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Diphenylene iodonium is an inhibitor of the respiratory burst-generating NADPH oxidase of phagocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2121828", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 861, "text": "NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oA\u00e2, suggesting that NADPH oxidase activation was involved in microglial activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229789", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 693, "text": "In addition, inhibitors of NADPH oxidase (diphenylene iodonium or apocynin) also prevented microglia proliferation, suggesting that this may be the source of hydrogen peroxide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16393992", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 861, "text": "Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, D-(+)-neopterine) also significantly blunted the generation of reactive oxygen species, activation of K(+), Cl(-)-cotransport and apoptosis induced by N-ethylmaleimide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11755128", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 454, "text": "With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12424096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "NADPH-dependent superoxide production by the solubilized oxidase of neutrophils was inhibited 36% by diphenylene iodonium at a 1:1 stoichiometry with the enzyme flavoprotein content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3800872", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1249, "text": "These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oA\u03b2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229789", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 941, "text": "Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19892012", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 747, "text": "Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046555", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 453, "text": "With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12424096", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 745, "text": "UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15308331", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1121, "text": "In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20698853", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 955, "text": "Such discharge of Dectin-1-reactive \u03b2-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503982", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1056, "text": "The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17341601", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1385, "text": "ANG II further increased superoxide production in LP only, and this was inhibited by coincubation with diphenylene iodonium or apocynin (inhibitor of NADPH oxidase complex)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16741139", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 973, "text": "Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (G\u00f66976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCalpha, Src, p47(phox), p300, and HDAC4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19281832", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 640, "text": "Here we show that cAMP-dependent decidualization can be attenuated or enhanced upon treatment of primary cultures with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenylen iodonium) or activator (apocynin), respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159852", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 455, "text": "With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12424096", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 1011, "text": "The inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15845907", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1155, "text": "Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662968", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 749, "text": "Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046555", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 626, "text": "The G6PD inhibitor DHEA and the inhibitors of NADPH oxidase apocynin and diphenylene iodonium (DPI) prevented both superoxide generation and capacitation in human spermatozoa, but whereas DPI and DHEA inhibited PPP, apocynin did not influence it, suggesting that PPP activation during capacitation is not a response to increased oxidative stress but exerts a role by supplying reducing equivalents to oxygen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19819434", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 809, "text": "Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15271858", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1154, "text": "Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662968", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1122, "text": "In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20698853", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1250, "text": "These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oA\u03b2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229789", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 748, "text": "Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046555", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 746, "text": "UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15308331", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 956, "text": "Such discharge of Dectin-1-reactive \u03b2-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503982", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 910, "text": "Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (G\u00f66976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19281832", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 942, "text": "Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19892012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The use of diphenylene iodonium, an inhibitor of NADPH oxidase, to investigate the antimicrobial action of human monocyte derived macrophages.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2121828", "endSection": "title" }, { "offsetInBeginSection": 628, "offsetInEndSection": 861, "text": "NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oA\u03b2, suggesting that NADPH oxidase activation was involved in microglial activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229789", "endSection": "abstract" }, { "offsetInBeginSection": 930, "offsetInEndSection": 1215, "text": "Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794531", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 664, "text": "We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4-(2-amino-ethyl)-benzolsulphonyl-fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20860666", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 939, "text": "IL-1beta and TNF-alpha rapidly stimulated the rate of hydrogen peroxide produced by isolated microglia, and this was inhibited by diphenylene iodonium, implying that the cytokines were acting directly on microglia to stimulate the NADPH oxidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16393992", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1224, "text": "The fractions achieved the same effects that known NADPH oxidase inhibitors, such as diphenylene iodonium and apocynin, but they presented better hydrosolubility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22134950", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 808, "text": "Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15271858", "endSection": "abstract" } ] }, { "body": "Viliuisk encephalomyelitis is diagnosed in which geographical area?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7848104", "http://www.ncbi.nlm.nih.gov/pubmed/20010208", "http://www.ncbi.nlm.nih.gov/pubmed/19618339", "http://www.ncbi.nlm.nih.gov/pubmed/1393513", "http://www.ncbi.nlm.nih.gov/pubmed/15182325", "http://www.ncbi.nlm.nih.gov/pubmed/18379734", "http://www.ncbi.nlm.nih.gov/pubmed/9223130", "http://www.ncbi.nlm.nih.gov/pubmed/2894813", "http://www.ncbi.nlm.nih.gov/pubmed/18252102", "http://www.ncbi.nlm.nih.gov/pubmed/24586232" ], "ideal_answer": [ "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic." ], "exact_answer": [ "Northeast Siberia" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:640", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004679" ], "type": "factoid", "id": "588f9f83ed9bbee70d000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND: Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Communicating hydrocephalus following eosinophilic meningitis is pathogenic for chronic Viliuisk encephalomyelitis in Northeastern Siberia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586232", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Epidemiology of Viliuisk encephalomyelitis in Eastern Siberia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010208", "endSection": "title" }, { "offsetInBeginSection": 245, "offsetInEndSection": 350, "text": ". An epidemic of this disease has been spreading throughout the Yakut Republic of the Russian Federation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010208", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 729, "text": "METHODS: Detailed clinical, pathologic, laboratory, and epidemiologic studies have identified 414 patients with definite Viliuisk encephalomyelitis in 15 of 33 administrative regions of the Yakut Republic between 1940 and 1999.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Viliuisk encephalomyelitis in Eastern Siberia - analysis of 390 cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19618339", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Viliuisk encephalomyelitis (VE) is a unique disease occurring in the Yakut (Sakha) population of Eastern Siberia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19618339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Viliuisk encephalomyelitis in Northeastern Siberia is not caused by Borrelia burgdorferi infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18379734", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeastern Siberia and generally believed to be a chronic encephalomyelitis of unknown origin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18379734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeastern Siberia and generally believed to be a chronic encephalomyelitis of unknown origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18379734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Viliuisk encephalomyelitis in the Iakut people of Siberia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1393513", "endSection": "title" }, { "offsetInBeginSection": 727, "offsetInEndSection": 983, "text": "Initially identified in a small Yakut-Evenk population on the Viliui River of eastern Siberia, the disease subsequently spread through human contacts to new geographic areas, thus characterizing Viliuisk encephalomyelitis as an emerging infectious disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18252102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Viliuisk encephalomyelitis (VE) is an unique neurological disease occurring in the Iakut (Sakha) people of Siberia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9223130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Viliuisk encephalomyelitis (VEM) appears to be endemic disease, affecting native population in Yakutia (Yakut, Even, Evenk).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7848104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 534, "text": "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic.In search for the pathophysiology and causative agent of VE, we performed a cross-sectional study on clinical, serological and neuroimaging data on chronic VE patients during two medical expeditions to three villages within the Viliuiski river basin in the Republic of Sakha in 2000 and to the capital Yakutsk in 2006", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586232", "endSection": "abstract" }, { "offsetInBeginSection": 732, "offsetInEndSection": 987, "text": "Initially identified in a small Yakut-Evenk population on the Viliui River of eastern Siberia, the disease subsequently spread through human contacts to new geographic areas, thus characterizing Viliuisk encephalomyelitis as an emerging infectious disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18252102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Viliuisk encephalomyelitis (VE) is a unique disease occurring in the Yakut (Sakha) population of Eastern Siberia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19618339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Viliuisk encephalomyelitis in Northeastern Siberia is not caused by Borrelia burgdorferi infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18379734", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeastern Siberia and generally believed to be a chronic encephalomyelitis of unknown origin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18379734", "endSection": "abstract" }, { "offsetInBeginSection": 732, "offsetInEndSection": 988, "text": "Initially identified in a small Yakut-Evenk population on the Viliui River of eastern Siberia, the disease subsequently spread through human contacts to new geographic areas, thus characterizing Viliuisk encephalomyelitis as an emerging infectious disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18252102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 535, "text": "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic.In search for the pathophysiology and causative agent of VE, we performed a cross-sectional study on clinical, serological and neuroimaging data on chronic VE patients during two medical expeditions to three villages within the Viliuiski river basin in the Republic of Sakha in 2000 and to the capital Yakutsk in 2006.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586232", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 926, "text": "IgG antibodies to HTLV-I were measured in the sera and/or cerebrospinal fluid from 82 Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia, 164 Guamanian normal controls, 10 patients with kuru from the Eastern Highlands of Papua New Guinea, 4 patients with Viliuisk encephalomyelitis from the Iakut region of eastern Siberia, 45 Italian patients with multiple sclerosis, and 56 patients with polymyositis (49 from the United States and 7 from Jamaica).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2894813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Viliuisk encephalomyelitis (VE), a progressive neurological disorder with a fatal outcome usually in several months to 6 yrs after disease onset, is seen only among the Iakut people of Siberia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1393513", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 731, "text": "Transmission to unrelated persons was documented in a densely populated region around the city of Yakutsk in which Viliuisk encephalomyelitis had not been previously known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18252102", "endSection": "abstract" }, { "offsetInBeginSection": 732, "offsetInEndSection": 989, "text": "Initially identified in a small Yakut-Evenk population on the Viliui River of eastern Siberia, the disease subsequently spread through human contacts to new geographic areas, thus characterizing Viliuisk encephalomyelitis as an emerging infectious disease..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18252102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Epidemiology of Viliuisk encephalomyelitis in Eastern Siberia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20010208", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Viliuisk encephalomyelitis in the Iakut people of Siberia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1393513", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Viliuisk encephalomyelitis in Eastern Siberia - analysis of 390 cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19618339", "endSection": "title" } ] }, { "body": "What are Septins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25293760", "http://www.ncbi.nlm.nih.gov/pubmed/23163726", "http://www.ncbi.nlm.nih.gov/pubmed/12023038", "http://www.ncbi.nlm.nih.gov/pubmed/8636235", "http://www.ncbi.nlm.nih.gov/pubmed/18586950", "http://www.ncbi.nlm.nih.gov/pubmed/11238387", "http://www.ncbi.nlm.nih.gov/pubmed/22815479", "http://www.ncbi.nlm.nih.gov/pubmed/18541672", "http://www.ncbi.nlm.nih.gov/pubmed/23204191", "http://www.ncbi.nlm.nih.gov/pubmed/8791410", "http://www.ncbi.nlm.nih.gov/pubmed/27473901", "http://www.ncbi.nlm.nih.gov/pubmed/17922164", "http://www.ncbi.nlm.nih.gov/pubmed/24367716", "http://www.ncbi.nlm.nih.gov/pubmed/27048593", "http://www.ncbi.nlm.nih.gov/pubmed/16857012", "http://www.ncbi.nlm.nih.gov/pubmed/27044893", "http://www.ncbi.nlm.nih.gov/pubmed/24664283", "http://www.ncbi.nlm.nih.gov/pubmed/22767579", "http://www.ncbi.nlm.nih.gov/pubmed/20517926", "http://www.ncbi.nlm.nih.gov/pubmed/26051489", "http://www.ncbi.nlm.nih.gov/pubmed/26700173", "http://www.ncbi.nlm.nih.gov/pubmed/21824004", "http://www.ncbi.nlm.nih.gov/pubmed/26780475", "http://www.ncbi.nlm.nih.gov/pubmed/15214843", "http://www.ncbi.nlm.nih.gov/pubmed/24768753", "http://www.ncbi.nlm.nih.gov/pubmed/14517318", "http://www.ncbi.nlm.nih.gov/pubmed/20885997", "http://www.ncbi.nlm.nih.gov/pubmed/10607590", "http://www.ncbi.nlm.nih.gov/pubmed/21082023", "http://www.ncbi.nlm.nih.gov/pubmed/21883761", "http://www.ncbi.nlm.nih.gov/pubmed/25217462", "http://www.ncbi.nlm.nih.gov/pubmed/18826657", "http://www.ncbi.nlm.nih.gov/pubmed/25575596", "http://www.ncbi.nlm.nih.gov/pubmed/25957401" ], "ideal_answer": [ "Septins are an evolutionarily conserved family of GTP-binding proteins. They are involved in diverse processes including cytokinesis, apoptosis, infection, neurodegeneration and neoplasia. In yeast, septins assemble into a highly ordered array of filaments at the mother bud neck in Saccharomyces cerevisiae cells. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear.", "Septins are an evolutionarily conserved family of GTP-binding proteins. discover that septins, a component of the cytoskeleton, recognize membrane curvature at the micron scale, a common morphological hallmark of eukaryotic cellular processes. eptins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. " ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058112" ], "type": "summary", "id": "58a327bf60087bc10a000011", "snippets": [ { "offsetInBeginSection": 154, "offsetInEndSection": 325, "text": "discover that septins, a component of the cytoskeleton, recognize membrane curvature at the micron scale, a common morphological hallmark of eukaryotic cellular processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27044893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Septins are an evolutionarily conserved family of GTP-binding proteins. They are involved in diverse processes including cytokinesis, apoptosis, infection, neurodegeneration and neoplasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26700173", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 346, "text": "eptins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048593", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 386, "text": "nidulans septins contain the highly conserved GTP binding and coiled-coil domains seen in other septins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11238387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "The septins: roles in cytokinesis and other processes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8791410", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The septins are a novel family of proteins that were first recognized in yeast as proteins associated with the neck filaments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8791410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Septin9 is involved in septin filament formation and cellular stability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21824004", "endSection": "title" }, { "offsetInBeginSection": 703, "offsetInEndSection": 881, "text": "Here, we review these findings and discuss emerging mechanisms by which septins promote cell asymmetry in fungi and animals.\u00a9 2011 John Wiley & Sons A/S.\u00a9 The Author(s) 2015", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "DENdb: database of integrated human enhancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342387", "endSection": "title" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1101, "text": "Database URL: http://www.cbrc.kaust.edu.sa/dendb/..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342387", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 447, "text": "We developed DENdb, a centralized on-line repository of predicted enhancers derived from multiple human cell-lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342387", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1049, "text": "DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342387", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 602, "text": "DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342387", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 916, "text": "DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342387", "endSection": "abstract" } ] }, { "body": "List scales that are used for scoring of patients with spinal metastasis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24212518", "http://www.ncbi.nlm.nih.gov/pubmed/23179121", "http://www.ncbi.nlm.nih.gov/pubmed/27018903", "http://www.ncbi.nlm.nih.gov/pubmed/26713145", "http://www.ncbi.nlm.nih.gov/pubmed/26160329", "http://www.ncbi.nlm.nih.gov/pubmed/24912121", "http://www.ncbi.nlm.nih.gov/pubmed/21223698", "http://www.ncbi.nlm.nih.gov/pubmed/25869337", "http://www.ncbi.nlm.nih.gov/pubmed/27584676", "http://www.ncbi.nlm.nih.gov/pubmed/27080411", "http://www.ncbi.nlm.nih.gov/pubmed/18787846", "http://www.ncbi.nlm.nih.gov/pubmed/26602195", "http://www.ncbi.nlm.nih.gov/pubmed/24120144", "http://www.ncbi.nlm.nih.gov/pubmed/24869611", "http://www.ncbi.nlm.nih.gov/pubmed/25085251" ], "ideal_answer": [ "Tokuhashi, Tomita, Bauer, and Oswestry scores are used for survival prediction of patients with spinal metastases." ], "exact_answer": [ [ "Tokuhashi" ], [ "Tomita" ], [ "Bauer" ], [ "Oswestry" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009362" ], "type": "list", "id": "589a245878275d0c4a000025", "snippets": [ { "offsetInBeginSection": 556, "offsetInEndSection": 682, "text": "METHODS: Outcomes of surgery, prognostic factors for survival, and relevance of Tomita and Tokuhashi scores were investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24120144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "PURPOSE: To assess variability in the use of Tomita and modified Bauer scores in spine metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25869337", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1213, "text": "Only the Tomita scoring system was shown to be an independent prognostic factor for overall survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26713145", "endSection": "abstract" }, { "offsetInBeginSection": 1359, "offsetInEndSection": 1462, "text": ".CONCLUSION: The Tomita scoring system represents a practicable and highly predictive prognostic tool. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26713145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Analysis of the predictive role and new proposal for surgical strategies based on the modified Tomita and Tokuhashi scoring systems for spinal metastasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25085251", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 276, "text": "We also aimed to evaluate the validity of the prognostic scores in the Tomita and Tokuhashi systems and discuss several aspects to improve the predictive accuracy of these systems. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25085251", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1612, "text": "CONCLUSIONS: Tomita scores more accurately predicted survival than Tokuhashi scores. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25085251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "A comparison of the modified Tokuhashi and Tomita scores in determining prognosis for patients afflicted with spinal metastasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869611", "endSection": "title" }, { "offsetInBeginSection": 103, "offsetInEndSection": 215, "text": " It is for this reason that scoring systems, such as the modified Tokuhashi and Tomita scores, have been created", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869611", "endSection": "abstract" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1497, "text": "The modified Tokuhashi score had better accuracy in determining actual survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869611", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 316, "text": "Tokuhashi, Tomita, Bauer, and Oswestry scores have been devised for survival prediction; however, none of these systems have been evaluated in nasopharyngeal carcinoma (NPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24912121", "endSection": "abstract" }, { "offsetInBeginSection": 2366, "offsetInEndSection": 2491, "text": "All four scoring systems could be used to prognosticate these patients. The modified Tokuhashi score is the best in doing so.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24912121", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1399, "text": "Primary tumor type and Tokuhashi score independently predicted survival in patients with spinal metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23179121", "endSection": "abstract" }, { "offsetInBeginSection": 1586, "offsetInEndSection": 1710, "text": " Primary tumor type and Tokuhashi scoring independently predicted survival in patients with spinal metastases after surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23179121", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1133, "text": "A predictive score was then developed and compared against that of the modified Bauer score alone in terms of prognosticating 1-year survival after surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26160329", "endSection": "abstract" }, { "offsetInBeginSection": 2301, "offsetInEndSection": 2456, "text": "Our predictive score performed better than the modified Bauer alone and may be used to predict survival after surgical intervention for metastatic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26160329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Tokuhashi Scoring System has limited applicability in the majority of patients with spinal cord compression secondary to vertebral metastasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212518", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Tokuhashi Scoring System has limited applicability in the majority of patients with spinal cord compression secondary to vertebral metastasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24212518", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 704, "text": "Tokuhashi, Tomita, Bauer, and Oswestry scores have been devised for survival prediction; however, none of these systems have been evaluated in nasopharyngeal carcinoma (NPC).To investigate the accuracy of these scoring systems in predicting survival and to identify prognostic factors for survival of the patients with spinal metastases from NPC.Retrospective analysis of the patients with spinal metastases from NPC who were treated in our institution.The study included 87 patients with spinal metastases from NPC.The primary outcome measure was the survival time of these patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24912121", "endSection": "abstract" }, { "offsetInBeginSection": 2083, "offsetInEndSection": 2267, "text": "Predictive value of survival by modified Tokuhashi score was the highest among all four scoring systems.Patients with spinal metastases from NPC have relatively good survival prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24912121", "endSection": "abstract" }, { "offsetInBeginSection": 1748, "offsetInEndSection": 1994, "text": "The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18787846", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 423, "text": "A retrospective study of 180 patients with lung cancer spinal metastases, wherein prognostic score-predicted survival was compared with actual survival.To evaluate and compare the accuracy of prognostic scoring systems in lung cancer spinal metastases.The modified Tokuhashi, Tomita, modified Bauer, and Oswestry scores are currently used to guide decisions regarding operative treatment of patients with spinal metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27018903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "To evaluate the predictive values of Tokuhashi score, revised Tokuhashi score and Tomita score systems for life expectancy and treatment options in patients with spinal metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21223698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "A comparison of the modified Tokuhashi and Tomita scores in determining prognosis for patients afflicted with spinal metastasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869611", "endSection": "title" }, { "offsetInBeginSection": 1789, "offsetInEndSection": 1975, "text": "The combination of Tokuhashi score and Tomita score may be applied to better predict postoperative survival prognosis and guide the surgical options for patients with spinal metastasis..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21223698", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 441, "text": "reported a composite model taking into account a modified Bauer score, preoperative albumin, and ambulatory status of patients with spinal metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27080411", "endSection": "abstract" } ] }, { "body": "Does NADPH oxidase 5 require any subunit for function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21319793", "http://www.ncbi.nlm.nih.gov/pubmed/15994299" ], "ideal_answer": [ "No, NADPH oxidase 5 (NOX5) does not require any subunits for function." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0016175", "http://www.biosemantics.org/jochem#4270191", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019255", "http://amigo.geneontology.org/amigo/term/GO:0016174", "http://www.uniprot.org/uniprot/NOXO1_HUMAN", "http://www.uniprot.org/uniprot/NOX5_HUMAN" ], "type": "yesno", "id": "58a5add260087bc10a000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Nox5 forms a functional oligomer mediated by self-association of its dehydrogenase domain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21319793", "endSection": "title" }, { "offsetInBeginSection": 290, "offsetInEndSection": 399, "text": " While Nox1-4 require regulatory subunits, including p22phox, Nox5 activity does not depend on any subunits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21319793", "endSection": "abstract" }, { "offsetInBeginSection": 1566, "offsetInEndSection": 1678, "text": " Thus, Nox5 forms a catalytically active oligomer in the membrane that is mediated by its dehydrogenase domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21319793", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 934, "text": "Coexpression of specific Nox catalytic subunits (Nox1, Nox2, Nox3, Nox4, or Nox5) along with their corresponding regulatory subunits (NOXO1/NOXA1 for Nox1; p47phox/p67phox/Rac for Nox2; NOXO1 for Nox3; no subunits for Nox4 or Nox5) resulted in marked production of reactive oxygen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15994299", "endSection": "abstract" } ] }, { "body": "What are the side effects during statins administration in patients with atherosclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25678839", "http://www.ncbi.nlm.nih.gov/pubmed/26575138", "http://www.ncbi.nlm.nih.gov/pubmed/21796961", "http://www.ncbi.nlm.nih.gov/pubmed/21267417", "http://www.ncbi.nlm.nih.gov/pubmed/12891851", "http://www.ncbi.nlm.nih.gov/pubmed/19039148", "http://www.ncbi.nlm.nih.gov/pubmed/17042673", "http://www.ncbi.nlm.nih.gov/pubmed/21972203", "http://www.ncbi.nlm.nih.gov/pubmed/25644328", "http://www.ncbi.nlm.nih.gov/pubmed/27878791", "http://www.ncbi.nlm.nih.gov/pubmed/24788803", "http://www.ncbi.nlm.nih.gov/pubmed/24840269", "http://www.ncbi.nlm.nih.gov/pubmed/24601937", "http://www.ncbi.nlm.nih.gov/pubmed/25936326", "http://www.ncbi.nlm.nih.gov/pubmed/18585718", "http://www.ncbi.nlm.nih.gov/pubmed/22913216", "http://www.ncbi.nlm.nih.gov/pubmed/23299641", "http://www.ncbi.nlm.nih.gov/pubmed/26490078" ], "ideal_answer": [ "The side effects during statins administration in patients with atherosclerosis are:\n1) Myopathy\n2) Transaminase elevations\n3) Diabetes mellitus \n4) Renal and neurologic adverse effects." ], "exact_answer": [ [ "Myopathy" ], [ "Transaminase elevations" ], [ "Diabetes mellitus" ], [ "Renal adverse effects" ], [ "Neurologic adverse effects" ] ], "type": "list", "id": "589c4c9078275d0c4a000040", "snippets": [ { "offsetInBeginSection": 1081, "offsetInEndSection": 1224, "text": "A history of side effects was reported by 40 (19.5%) of the patients, and mainly consisted of muscle complaints and gastrointestinal symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25644328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Treatment Options for Statin-Associated Muscle Symptoms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26575138", "endSection": "title" }, { "offsetInBeginSection": 383, "offsetInEndSection": 457, "text": "Muscle symptoms are a clinically relevant side effect of statin treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26575138", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 727, "text": "At least 5% of patients taking statins have statin-associated muscle symptoms (SAMS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26575138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Muscle problems and other adverse symptoms associated with statin use are frequent reasons for non-adherence and discontinuation of statin therapy, which results in inadequate control of hyperlipidemia and increased cardiovascular risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26490078", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 838, "text": "It was estimated that rosuvastatin-associated absolute hazards of muscle-, liver- and renal-related adverse effects are lower than the corresponding vascular benefits in moderate vascular risk individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24788803", "endSection": "abstract" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1856, "text": "Rosuvastatin-induced proteinuria appears to be of tubular origin, not relating to kidney injury. Rosuvastatin increases the risk of new-onset diabetes by dose-dependently impairing insulin sensitivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24788803", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 736, "text": "Statins are associated with myopathy, transaminase elevations, and an increased risk of incident diabetes mellitus among some patients; connections between statins and other processes, such as renal and neurologic function, have also been studied with mixed results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24840269", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 696, "text": "Muscle symptoms are a clinically relevant side effect of statin treatment.This review is based on pertinent publications retrieved by a selective literature search, and on the current recommendations of the European Atherosclerosis Society.At least 5% of patients taking statins have statin-associated muscle symptoms (SAMS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26575138", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1239, "text": "Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23299641", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1311, "text": "Better understanding of the molecular mechanisms involved in statin-induced myopathy may help identify patient groups susceptible to statins' side effects, thereby increasing their safety..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18585718", "endSection": "abstract" } ] }, { "body": "Entresto is composed of which two drugs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27697814", "http://www.ncbi.nlm.nih.gov/pubmed/26642078", "http://www.ncbi.nlm.nih.gov/pubmed/26976916", "http://www.ncbi.nlm.nih.gov/pubmed/27284124", "http://www.ncbi.nlm.nih.gov/pubmed/26417173", "http://www.ncbi.nlm.nih.gov/pubmed/26992459", "http://www.ncbi.nlm.nih.gov/pubmed/26975167", "http://www.ncbi.nlm.nih.gov/pubmed/26466333", "http://www.ncbi.nlm.nih.gov/pubmed/27378659", "http://www.ncbi.nlm.nih.gov/pubmed/27804100", "http://www.ncbi.nlm.nih.gov/pubmed/26873495" ], "ideal_answer": [ "Entresto is composed of sacubitril and valsartan. It is newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure." ], "exact_answer": [ [ "sacubitril" ], [ "valsartan" ] ], "type": "list", "id": "58962ed178275d0c4a000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "The PARADIGM-HF study, a large outcome trial in heart failure and reduced ejection fraction (HFrEF), has recently shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto\u00ae, Novartis), still commonly referred to as LCZ696, compared to ACE-inhibitor therapy, possibly leading us to a new era for heart failure (HF) treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26642078", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 627, "text": "This article reviews the background, current knowledge and data supporting the use of sacubitril/valsartan (Entresto(\u00ae) ), the newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26992459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "\u25bc Sacubitril valsartan (Entresto-Novartis) is a new oral drug licensed for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27284124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Rhabdomyolysis After Coadministration of Atorvastatin and Sacubitril/Valsartan (Entresto\u2122) in a 63-Year-Old Woman.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27804100", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 367, "text": "A 63-year-old woman previously stable on a regimen of atorvastatin 40\u00a0mg daily, carvedilol 25\u00a0mg twice daily, digoxin 0.125\u00a0mg daily, furosemide 40\u00a0mg daily, spironolactone 25\u00a0mg daily, rivaroxaban 15\u00a0mg daily, and enalapril 20\u00a0mg twice daily for heart failure developed rhabdomyolysis 26\u00a0days after enalapril was stopped and sacubitril/valsartan (Entresto\u2122) started.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27804100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Sacubitril/valsartan [LCZ696 (Entresto), Novartis Pharmaceuticals Corp.] is the first in a new class of drugs that combines neprilysin inhibition with angiotensin II receptor antagonism, the combination of which acts to increase endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26466333", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 669, "text": "In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26976916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Sacubitril/valsartan (Entresto) for chronic heart failure; brexpiprazole (Rexulti) for major depressive disorder and schizophrenia; and lumacaftor/ivacaftor (Orkambi) for cystic fibrosis involving specific CFTR mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26417173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Sacubritil\u2217valsartan (Entresto, Novartis, still commonly referred to as LCZ696) is a combination drug described as a new class of dual-acting angiotensin receptor-neprilysin inhibitor (ARNi).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27378659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The molecular combination of sacubitril and valsartan (Entresto) is a new drug for reducing the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26975167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "\u25bc Sacubitril valsartan (Entresto-Novartis) is a new oral drug licensed for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction.(1) It is described as an angiotensin receptor neprilysin inhibitor and contains the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan.(1-3) Here, we review the evidence for sacubitril valsartan and consider its place in the management of heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27284124", "endSection": "abstract" } ] }, { "body": "What is the doRiNA database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25416797", "http://www.ncbi.nlm.nih.gov/pubmed/22086949" ], "ideal_answer": [ "doRina is a database of RNA interactions in post-transcriptional regulation." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030561", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012323" ], "type": "summary", "id": "588f365194c1512c50000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "doRiNA: a database of RNA interactions in post-transcriptional regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "title" }, { "offsetInBeginSection": 394, "offsetInEndSection": 1242, "text": " We provide a database that supports the quest for deciphering this regulatory code. Within doRiNA, we are systematically curating, storing and integrating binding site data for RBPs and miRNAs. Users are free to take a target (mRNA) or regulator (RBP and/or miRNA) centric view on the data. We have implemented a database framework with short query response times for complex searches (e.g. asking for all targets of a particular combination of regulators). All search results can be browsed, inspected and analyzed in conjunction with a huge selection of other genome-wide data, because our database is directly linked to a local copy of the UCSC genome browser. At the time of writing, doRiNA encompasses RBP data for the human, mouse and worm genomes. For computational miRNA target site predictions, we provide an update of PicTar predictions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "DoRiNA 2.0--upgrading the doRiNA database of RNA interactions in post-transcriptional regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25416797", "endSection": "title" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1140, "text": "At the time of writing, doRiNA encompasses RBP data for the human, mouse and worm genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 584, "text": "Within doRiNA, we are systematically curating, storing and integrating binding site data for RBPs and miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "doRiNA: a database of RNA interactions in post-transcriptional regulation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "title" }, { "offsetInBeginSection": 479, "offsetInEndSection": 587, "text": "Within doRiNA, we are systematically curating, storing and integrating binding site data for RBPs and miRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 1059, "offsetInEndSection": 1148, "text": "At the time of writing, doRiNA encompasses RBP data for the human, mouse and worm genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 589, "text": "Within doRiNA, we are systematically curating, storing and integrating binding site data for RBPs and miRNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 1059, "offsetInEndSection": 1150, "text": "At the time of writing, doRiNA encompasses RBP data for the human, mouse and worm genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 588, "text": "Within doRiNA, we are systematically curating, storing and integrating binding site data for RBPs and miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 1059, "offsetInEndSection": 1149, "text": "At the time of writing, doRiNA encompasses RBP data for the human, mouse and worm genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "DoRiNA 2.0--upgrading the doRiNA database of RNA interactions in post-transcriptional regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25416797", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "doRiNA: a database of RNA interactions in post-transcriptional regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086949", "endSection": "title" } ] }, { "body": "Is NSD-1015 an inhibitor of Aromatic L-Amino Acid Decarboxylase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7664818", "http://www.ncbi.nlm.nih.gov/pubmed/20501080", "http://www.ncbi.nlm.nih.gov/pubmed/2320657", "http://www.ncbi.nlm.nih.gov/pubmed/323424", "http://www.ncbi.nlm.nih.gov/pubmed/6164221", "http://www.ncbi.nlm.nih.gov/pubmed/8371833", "http://www.ncbi.nlm.nih.gov/pubmed/6811255", "http://www.ncbi.nlm.nih.gov/pubmed/8836582", "http://www.ncbi.nlm.nih.gov/pubmed/1348847", "http://www.ncbi.nlm.nih.gov/pubmed/15927700", "http://www.ncbi.nlm.nih.gov/pubmed/10619466", "http://www.ncbi.nlm.nih.gov/pubmed/8361951", "http://www.ncbi.nlm.nih.gov/pubmed/6432557", "http://www.ncbi.nlm.nih.gov/pubmed/8511717", "http://www.ncbi.nlm.nih.gov/pubmed/7616241", "http://www.ncbi.nlm.nih.gov/pubmed/1997008", "http://www.ncbi.nlm.nih.gov/pubmed/24084697", "http://www.ncbi.nlm.nih.gov/pubmed/1904482", "http://www.ncbi.nlm.nih.gov/pubmed/3917287", "http://www.ncbi.nlm.nih.gov/pubmed/11135014", "http://www.ncbi.nlm.nih.gov/pubmed/1470299", "http://www.ncbi.nlm.nih.gov/pubmed/2426412", "http://www.ncbi.nlm.nih.gov/pubmed/20408420", "http://www.ncbi.nlm.nih.gov/pubmed/7692885", "http://www.ncbi.nlm.nih.gov/pubmed/22841861", "http://www.ncbi.nlm.nih.gov/pubmed/2414683", "http://www.ncbi.nlm.nih.gov/pubmed/6780662", "http://www.ncbi.nlm.nih.gov/pubmed/6746835", "http://www.ncbi.nlm.nih.gov/pubmed/12658372", "http://www.ncbi.nlm.nih.gov/pubmed/16292508", "http://www.ncbi.nlm.nih.gov/pubmed/8287902", "http://www.ncbi.nlm.nih.gov/pubmed/26830512", "http://www.ncbi.nlm.nih.gov/pubmed/7690229", "http://www.ncbi.nlm.nih.gov/pubmed/17066255", "http://www.ncbi.nlm.nih.gov/pubmed/23940784", "http://www.ncbi.nlm.nih.gov/pubmed/1663587", "http://www.ncbi.nlm.nih.gov/pubmed/904693", "http://www.ncbi.nlm.nih.gov/pubmed/11343835", "http://www.ncbi.nlm.nih.gov/pubmed/3103858", "http://www.ncbi.nlm.nih.gov/pubmed/7889269", "http://www.ncbi.nlm.nih.gov/pubmed/1436125", "http://www.ncbi.nlm.nih.gov/pubmed/8096696", "http://www.ncbi.nlm.nih.gov/pubmed/19168057" ], "ideal_answer": [ "Yes, NSD-1015 is an ihnibitor of Aromatic L-Amino Decarboxylase." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0004058", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4251263", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065105", "http://www.biosemantics.org/jochem#4251263", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024322", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001142" ], "type": "yesno", "id": "589c334e78275d0c4a00003d", "snippets": [ { "offsetInBeginSection": 1341, "offsetInEndSection": 1550, "text": "When pretreated with a central AADC inhibitor (NSD-1015), further application of l-dopa failed to increase the motoneuron activity although the expression of DA in the AADC cells was not completely inhibited. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26830512", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 739, "text": "Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940784", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 577, "text": "We evaluated this in vivo by reverse dialysis of the aromatic-l-amino-acid decarboxylase (EC 4.1.1.28) inhibitor NSD-1015 (20\u03bcM) and selected concentrations of l- or d-tyrosine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841861", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 296, "text": "Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20408420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "To establish the neurotransmitter role(s) of L-3,4-dihydroxyphenylalanine (DOPA) in its own right, we attempted to clarify whether i.p. injection of a DOPA antagonist, DOPA cyclohexyl ester (CHE), would antagonize the behavioral responses of conscious rats to DOPA in the presence of 3-hydroxybenzylhydrazine (NSD-1015) (100 mg/kg i.p.), a central aromatic L-amino acid decarboxylase (AADC) inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19168057", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 459, "text": "TH and TPH activities were determined in tissue extracts by measuring the accumulation of L-Dopa and 5-HTP respectively, following the administration of the aromatic L-amino acid decarboxylase inhibitor, NSD-1015. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17066255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Results of a neurochemical study of the effects of the new anxiolytic drugs afobazole and ladasten on the synthesis and metabolism of monoamines and their metabolites determined by HPLC on the model of monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) in the brain structures of Wistar rats are reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20408420", "endSection": "abstract" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1397, "text": ". When pretreated with a central AADC inhibitor (NSD-1015)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26830512", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 848, "text": "NSD 1015 (general AADC inhibitor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24084697", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 289, "text": "monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20408420", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 520, "text": "the aromatic-l-amino-acid decarboxylase (EC 4.1.1.28) inhibitor NSD-1015", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "An accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of female rats treated with 3-hydroxybenzylhydrazine (NSD 1015), and inhibitor of aromatic L-amino acid decarboxylase (DOPA decarboxylase) activity, was associated with a decreased concentration of dopamine in the median eminence and pronounced reduction in the release of dopamine into hypophysial portal blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6811255", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 1019, "text": "6S-BH4 increased extracellular DOPA levels in the presence of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase (an index of in vivo tyrosine hydroxylase activity), to an extent similar to the increase induced by 6R-BH4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7616241", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 774, "text": "5-HT synthesis was estimated by measuring the accumulation of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in the neurointermediate lobe of male Long-Evans rats following the administration of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3103858", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 1062, "text": "Monoamine synthesis was studied in different parts of the brain by measuring the accumulated dopa and 5-hydroxytryptophan (5-HTP), 30 min after NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg) an inhibitor of aromatic L-amino-acid decarboxylase, given i.p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/904693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 377, "text": "HPLC coupled with electrochemical detection was used to make concurrent measurements of the rate of accumulation of 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine in selected brain regions (striatum, nucleus accumbens, septum, medial periventricular hypothalamus) and thoracic spinal cords of rats treated with NSD 1015, an inhibitor of aromatic-L-amino-acid decarboxylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3917287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 551, "text": "The activity of 5-hydroxytryptaminergic neurons has been estimated from measurements of: concentrations of 5-hydroxyindoleacetic acid; the ratio of the concentrations of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine; the rate of accumulation of 5-hydroxytryptophan following the administration of an aromatic L-amino acid decarboxylase inhibitor (e.g., NSD 1015); the rate of accumulation of 5-hydroxytryptamine, and the rate of decline of 5-hydroxyindoleacetic acid following the administration of a monoamine oxidase inhibitor (e.g., pargyline).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2426412", "endSection": "abstract" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1183, "text": "The accumulation of dopa (3,4-dihydroxyphenylalanine) after administration of NSD 1015 to inhibit aromatic l-amino acid decarboxylase was determined as an index of NE synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20501080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The central aromatic amino acid DOPA decarboxylase inhibitor, NSD-1015, does not inhibit L-DOPA-induced circling in unilateral 6-OHDA-lesioned-rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11135014", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3-hydroxybenzyl hydrazine (NSD-1015), is widely used to study the neurotransmitter-like actions of L-DOPA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11135014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The aromatic amino acid decarboxylase inhibitor, NSD-1015, increases release of dopamine: response characteristics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1470299", "endSection": "title" }, { "offsetInBeginSection": 450, "offsetInEndSection": 549, "text": "The aromatic amino acid decarboxylase inhibitor NSD 1015 markedly increased the dopa concentration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6164221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "Using a microdialysis technique, the rat striatum was perfused with NSD-1015, an inhibitor of aromatic L-amino acid decarboxylase, and the amount of L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) accumulating in dialysate was measured as an index of in vivo activities of tyrosine hydroxylase and tryptophan hydroxylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7692885", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 489, "text": "Also, we studied the effect of MnCl2 on extracellular levels of l-Dopa in the presence of aromatic amino acid decarboxylase (AADC) inhibitor 3-hydroxybencilhydracine-HCl (NSD 1015).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16292508", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 283, "text": "The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8836582", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "An accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of female rats treated with 3-hydroxybenzylhydrazine (NSD 1015), and inhibitor of aromatic L-amino acid decarboxylase (DOPA decarboxylase) activity, was associated with a decreased concentration of dopamine in the median eminence and pronounced reduction in the release of dopamine into hypophysial portal blood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6811255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "[Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20408420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "DOPA was measured in the anterior pituitary and hypothalamic-hypophysial portal blood after treatment with NSD-1015, a DOPA decarboxylase inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1348847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Central action of an inhibitor of brain dopa-decarboxylase, NSD-1015, on cyanamide-induced alcohol drinking in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2320657", "endSection": "title" }, { "offsetInBeginSection": 102, "offsetInEndSection": 284, "text": "The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8836582", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3-hydroxybenzyl hydrazine (NSD-1015), is widely used to study the neurotransmitter-like actions of L-DOPA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11135014", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 944, "text": "Furthermore, the ethanol-induced enhancement of 3,4-dihydroxyphenylalanine accumulation in the mesolimbic dopamine terminal area after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/kg) that exerted no effects per se.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8287902", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 630, "text": "The acetylcholinesterase inhibitor physostigmine (0.5 mg/kg s.c.) enhanced L-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in both the corpus striatum and limbic areas (nucleus accumbens) after inhibition of aromatic amino acid decarboxylase with NSD-1015, indicating an enhanced synthesis of dopamine in these brain regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1436125", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1376, "text": "Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid decarboxylase whereas methylene blue did not affect anterior pituitary DOPA accumulation when compared to controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11343835", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 433, "text": "The accumulation of dihydroxyphenylalanine (DOPA) following administration of the L-aromatic amino acid decarboxylase inhibitor, NSD 1015, was used to estimate DA synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6432557", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1189, "text": "Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7889269", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 482, "text": "After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L-amino acid decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015; 100 mg/kg, ip).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8511717", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 633, "text": "Following motor activity observations, the cerebral aromatic L-amino acid decarboxylase inhibitor NSD-1015 (100 mg kg-1 intraperitoneally) was administered and 30 min. later the animals were decapitated for subsequent analysis of the accumulated forebrain DOPA and 5-HTP levels, as an estimate of the rate of monoamine synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8361951", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 834, "text": "The utility of this technique was demonstrated by comparing the effects on the scans of halothane and pentobarbital anesthesia and by the administration of NSD 1015, a peripheral and central inhibitor of L-aromatic amino-acid decarboxylase, between back-to-back scans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1904482", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 571, "text": "Addition of the aromatic amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine (NSD 1015), prevented the formation of N-acetylcompounds from L-[3H]tyrosine, without resulting in an accumulation of label in L-DOPA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6780662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "The effects of the peripheral aromatic amino acid decarboxylase (AADC) inhibitors, carbidopa and benserazide, and the central AADC inhibitor, 3-hydroxybenzylhydrazine (NSD-1015) on peripheral and brain monoamine oxidase (MAO) A and B activity were investigated in the rat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12658372", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1105, "text": "Although the putative role of NSD-1015 is as an aromatic amino acid decarboxylase inhibitor, the present results demonstrate that, either as a result of this function and/or in addition to this role, NSD-1015 is a potent activator of the release of dopamine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1470299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The aromatic amino acid decarboxylase inhibitor, NSD-1015, increases release of dopamine: response characteristics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1470299", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The central aromatic amino acid DOPA decarboxylase inhibitor, NSD-1015, does not inhibit L-DOPA-induced circling in unilateral 6-OHDA-lesioned-rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11135014", "endSection": "title" }, { "offsetInBeginSection": 472, "offsetInEndSection": 697, "text": "The L-aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine dihydrochloride) was then given ICV twice daily in a volume of 5.0 microliters in the following doses: 0.005, 0.01, 0.1 and 1.0 micrograms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2320657", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1106, "text": "Although the putative role of NSD-1015 is as an aromatic amino acid decarboxylase inhibitor, the present results demonstrate that, either as a result of this function and/or in addition to this role, NSD-1015 is a potent activator of the release of dopamine..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1470299", "endSection": "abstract" } ] }, { "body": "Is pseudouridine a RNA modification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25616362", "http://www.ncbi.nlm.nih.gov/pubmed/20106954", "http://www.ncbi.nlm.nih.gov/pubmed/15659360" ], "ideal_answer": [ "Yes, pseudouridine (\u03a8) is the most abundant of>150 nucleoside modifications in RNA." ], "exact_answer": "yes", "type": "yesno", "id": "58bbb77e22d3005309000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Pseudouridine (\u03a8) is the most abundant of>150 nucleoside modifications in RNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "The number and position of the pseudouridines of Haloarcula marismortui and Deinococcus radiodurans large subunit RNA have been determined by a combination of total nucleoside analysis by HPLC-mass spectrometry and pseudouridine sequencing by the reverse transcriptase method and by LC/MS/MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15659360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Pseudouridine is the most abundant of more than 100 chemically distinct natural ribonucleotide modifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20106954", "endSection": "abstract" } ] }, { "body": "What does the human ABCC gene product do?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16006996", "http://www.ncbi.nlm.nih.gov/pubmed/21799180", "http://www.ncbi.nlm.nih.gov/pubmed/16815813", "http://www.ncbi.nlm.nih.gov/pubmed/15631998", "http://www.ncbi.nlm.nih.gov/pubmed/19118502", "http://www.ncbi.nlm.nih.gov/pubmed/16357150", "http://www.ncbi.nlm.nih.gov/pubmed/18535159", "http://www.ncbi.nlm.nih.gov/pubmed/20712617", "http://www.ncbi.nlm.nih.gov/pubmed/18691054", "http://www.ncbi.nlm.nih.gov/pubmed/26191068", "http://www.ncbi.nlm.nih.gov/pubmed/12499391", "http://www.ncbi.nlm.nih.gov/pubmed/18668432", "http://www.ncbi.nlm.nih.gov/pubmed/18484914", "http://www.ncbi.nlm.nih.gov/pubmed/20360301", "http://www.ncbi.nlm.nih.gov/pubmed/21740521", "http://www.ncbi.nlm.nih.gov/pubmed/11483364" ], "ideal_answer": [ "The important drug resistance-conferring members belong to three subfamilies of the human ABC family; these are ABCB1 (MDR1/P-glycoprotein of subfamily ABCB), subfamily ABCC (MRPs), and ABCG2 (BCRP of subfamily ABCG), which are expressed in various organs. The ATP-binding cassette (ABC) transporters constitute a large family of membrane proteins, which transport a variety of compounds through the membrane against a concentration gradient at the cost of ATP hydrolysis" ], "exact_answer": [ "ATP dependent small molecule transporter" ], "type": "factoid", "id": "58c99fcc02b8c60953000029", "snippets": [ { "offsetInBeginSection": 616, "offsetInEndSection": 915, "text": "structure, function, and expression of the important drug resistance-conferring members belonging to three subfamilies of the human ABC family; these are ABCB1 (MDR1/P-glycoprotein of subfamily ABCB), subfamily ABCC (MRPs), and ABCG2 (BCRP of subfamily ABCG), which are expressed in various organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16815813", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 455, "text": "Transport proteins, including members of the multidrug resistance protein (MRP)/ABCC subfamily, have been recognized to contribute to the latter function. MRP5 (ABCC5) was identified as transmembrane transport protein for cyclic nucleotides, especially 3',5'-cyclic GMP (cGMP), indicating an additional role in signal transduction and a potential role in placenta development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15631998", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 791, "text": "According to the new nomenclature of human ABC transporter genes, the 'ABCC' gene sub-family comprises three classes involving multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and a cystic fibrosis transmembrane conductance regulator (CFTR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18668432", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 599, "text": "With the addition of these two genes, the complete human ABCC subfamily has 12 identified members (ABCC1-12), nine from the multidrug resistance-like subgroup, two from the sulfonylurea receptor subgroup, and the CFTR gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11483364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Identification and bioinformatic characterization of a multidrug resistance associated protein (ABCC) gene in Plasmodium berghei.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19118502", "endSection": "title" }, { "offsetInBeginSection": 89, "offsetInEndSection": 198, "text": "One major group of transporters is known as multidrug resistance associated proteins (MRP; ABCC gene family).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12499391", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 741, "text": "On the other hand, several human multidrug resistance proteins [human ATP-binding cassette transporter, subfamily C (ABCC)] cause resistance against nucleoside analogs and mediate transport of phosphorylated nucleoside derivatives out of the cells in an ATP-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20360301", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 796, "text": "According to the new nomenclature of human ABC transporter genes, the 'ABCC' gene sub-family comprises three classes involving multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and a cystic fibrosis transmembrane conductance regulator (CFTR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18668432", "endSection": "abstract" }, { "offsetInBeginSection": 1955, "offsetInEndSection": 2178, "text": "Several MRP/ABCC members (MRPs 1-3) are associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18691054", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1954, "text": "In vitro, the MRP/ABCC transporters can collectively confer resistance to natural product anticancer drugs and their conjugated metabolites, platinum compounds, folate antimetabolites, nucleoside and nucleotide analogs, arsenical and antimonial oxyanions, peptide-based agents, and in concert with alterations in phase II conjugating or biosynthetic enzymes, classical alkylating agents, alkylating agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18691054", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1219, "text": "The human MRP/ABCC transporters except MRP9/ABCC12 are all able to transport organic anions, such as drugs conjugated to glutathione, sulphate or glucuronate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18691054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "The ABCC multidrug resistance associated proteins (ABCC-MRP), a subclass of ABC transporters are involved in multiple physiological processes that include cellular homeostasis, metal detoxification, and transport of glutathione-conjugates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26191068", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 212, "text": "he ABCC subfamily of the ATP binding cassette (ABC) transporters, which were formerly known as multidrug resistance-related proteins (MRPs), consists of closely related members found in all eukaryotic organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20712617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "The ATP-binding cassette (ABC) transporters are a superfamily of membrane proteins that are best known for their ability to transport a wide variety of exogenous and endogenous substances across membranes against a concentration gradient via ATP hydrolysis. There are seven subfamilies of human ABC transporters, one of the largest being the 'C' subfamily (gene symbol ABCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21740521", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 642, "text": "Nine ABCC subfamily members, the so-called multidrug resistance proteins (MRPs) 1-9, have been implicated in mediating multidrug resistance in tumor cells to varying degrees as the efflux extrude chemotherapeutic compounds (or their metabolites) from malignant cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21740521", "endSection": "abstract" } ] }, { "body": "What is the connection between furin and hepcidin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "http://www.ncbi.nlm.nih.gov/pubmed/20634490", "http://www.ncbi.nlm.nih.gov/pubmed/24808863", "http://www.ncbi.nlm.nih.gov/pubmed/18664504", "http://www.ncbi.nlm.nih.gov/pubmed/17905609", "http://www.ncbi.nlm.nih.gov/pubmed/18775801", "http://www.ncbi.nlm.nih.gov/pubmed/23390091", "http://www.ncbi.nlm.nih.gov/pubmed/19610021" ], "ideal_answer": [ "The iron-regulatory peptide hepcidin is synthesized in the liver as an 84-aa pre-pro-hormone maturated by proteolysis through a consensus furin cleavage site to generate the bioactive 25-aa peptide secreted in the circulation. The hepatic prohormone convertase furin mediates the posttranslational processing of hepcidin." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045683", "http://www.uniprot.org/uniprot/HEPC_RAT", "http://www.uniprot.org/uniprot/HEPC_PONAB", "http://www.uniprot.org/uniprot/HEPC_MOUSE", "http://www.uniprot.org/uniprot/FURIN_BOVIN", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064451" ], "type": "summary", "id": "58bebc4c02b8c60953000015", "snippets": [ { "offsetInBeginSection": 101, "offsetInEndSection": 213, "text": "Hepcidin is mainly produced by the liver as a propeptide and processed by furin into the mature active peptide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24808863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Implication of the proprotein convertases in iron homeostasis: proprotein convertase 7 sheds human transferrin receptor 1 and furin activates hepcidin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390091", "endSection": "title" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1276, "text": "Analysis of primary hepatocytes from mice lacking furin, PC5, PACE4, or PC7 revealed that hepcidin, which limits iron availability in the circulation, is specifically generated by furin and not by PC7. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390091", "endSection": "abstract" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1604, "text": "Among the PC family members, only furin activates hepcidin in hepatocytes, and uniquely the full-length membrane-bound PC7 can directly shed hTfR1 by cleavage at Arg100 \u2193.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390091", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 815, "text": "The human hepcidin gene contains three exons that encode a 72-aa precursor (pro-hepcidin) with a characteristic furin cleavage site immediately N-terminal to the 25-aa major hepcidin species found in plasma and urine [3]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19610021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "title" }, { "offsetInBeginSection": 17, "offsetInEndSection": 392, "text": "The iron-regulatory peptide hepcidin is synthesized in the liver as an 84-aa pre-pro-hormone maturated by proteolysis through a consensus furin cleavage site to generate the bioactive 25-aa peptide secreted in the circulation. This peptide regulates iron export from enterocytes and macrophages by binding the membrane iron exporter, ferroportin, leading to its degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1451, "text": "Our results demonstrate that pro-hepcidin lacks biological activity, unless fully maturated by a furin-dependent process to yield the bioactive 25-aa peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17905609", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Hepcidin is encoded as an 84 amino acid prepropeptide containing a typical N-terminal 24 amino acid endoplasmic reticulum targeting signal sequence, and a 35 amino acid proregion (pro) with a consensus furin cleavage site immediately followed by the C-terminal 25 amino acid bioactive iron-regulatory hormone (mature peptide). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17905609", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1238, "text": "In conclusion, the hepatic prohormone convertase furin mediates the posttranslational processing of hepcidin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17905609", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1232, "text": "In conclusion, the hepatic prohormone convertase furin mediates the posttranslational processing of hepcidin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17905609", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1447, "text": "Furin in turn may control hepcidin expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20634490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Regulation of prohepcidin processing and activity by the subtilisin-like proprotein convertases Furin, PC5, PACE4 and PC7.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18664504", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "BACKGROUND/AIMS: The iron-regulatory peptide hepcidin is synthesized in the liver as an 84-aa pre-pro-hormone maturated by proteolysis through a consensus furin cleavage site to generate the bioactive 25-aa peptide secreted in the circulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1031, "text": "Furin activity was also modulated using furin inhibitor or siRNA-mediated furin mRNA knockdown.RESULTS: We found that pro-hepcidin could fully induce ferroportin degradation, but only when processed by furin to generate the mature hepcidin-25 form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 995, "text": "Furin activity was also modulated using furin inhibitor or siRNA-mediated furin mRNA knockdown.We found that pro-hepcidin could fully induce ferroportin degradation, but only when processed by furin to generate the mature hepcidin-25 form", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1808, "text": "CONCLUSIONS: These results demonstrate the key role of the convertases Furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin and suggest that the control of hepcidin processing as a potential therapeutic/diagnostic strategy in hepcidin-related disorders such as haemochromatosis, inflammatory diseases, anaemia and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18664504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "BACKGROUND/AIMS: The iron-regulatory peptide hepcidin is synthesized in the liver as an 84-aa pre-pro-hormone maturated by proteolysis through a consensus furin cleavage site to generate the bioactive 25-aa peptide secreted in the circulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1454, "text": "CONCLUSIONS: Our results demonstrate that pro-hepcidin lacks biological activity, unless fully maturated by a furin-dependent process to yield the bioactive 25-aa peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The iron-regulatory peptide hepcidin is synthesized in the liver as an 84-aa pre-pro-hormone maturated by proteolysis through a consensus furin cleavage site to generate the bioactive 25-aa peptide secreted in the circulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 996, "text": "Furin activity was also modulated using furin inhibitor or siRNA-mediated furin mRNA knockdown.We found that pro-hepcidin could fully induce ferroportin degradation, but only when processed by furin to generate the mature hepcidin-25 form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1393, "text": "Furin in turn may control hepcidin expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20634490", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1263, "text": "Analysis of primary hepatocytes from mice lacking furin, PC5, PACE4, or PC7 revealed that hepcidin, which limits iron availability in the circulation, is specifically generated by furin and not by PC7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390091", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1451, "text": "Furthermore, the mutated version of pro-hepcidin was completely inefficient at degrading ferroportin in macrophages.CONCLUSIONS: Our results demonstrate that pro-hepcidin lacks biological activity, unless fully maturated by a furin-dependent process to yield the bioactive 25-aa peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 782, "text": "However, the activity of the pro-peptide on ferroportin degradation has never been addressed.METHODS: To answer this question, we produced recombinant pro-hepcidin, both the wild-type form and a furin cleavage site mutant, and tested their activity on ferroportin levels in macrophagic J774 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 1350, "offsetInEndSection": 1397, "text": "Furin in turn may control hepcidin expression..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20634490", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 998, "text": "We found that pro-hepcidin could fully induce ferroportin degradation, but only when processed by furin to generate the mature hepcidin-25 form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17905609", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Implication of the proprotein convertases in iron homeostasis: proprotein convertase 7 sheds human transferrin receptor 1 and furin activates hepcidin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23390091", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19070914", "endSection": "title" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1754, "text": "These results demonstrate the key role of the convertases Furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin and suggest that the control of hepcidin processing as a potential therapeutic/diagnostic strategy in hepcidin-related disorders such as haemochromatosis, inflammatory diseases, anaemia and cancer..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18664504", "endSection": "abstract" } ] }, { "body": "Which cells express CIDEC protein in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20945533", "http://www.ncbi.nlm.nih.gov/pubmed/21636835", "http://www.ncbi.nlm.nih.gov/pubmed/25255829", "http://www.ncbi.nlm.nih.gov/pubmed/18845124", "http://www.ncbi.nlm.nih.gov/pubmed/26927378", "http://www.ncbi.nlm.nih.gov/pubmed/20596603", "http://www.ncbi.nlm.nih.gov/pubmed/23399566", "http://www.ncbi.nlm.nih.gov/pubmed/26770990", "http://www.ncbi.nlm.nih.gov/pubmed/18311595", "http://www.ncbi.nlm.nih.gov/pubmed/18509062", "http://www.ncbi.nlm.nih.gov/pubmed/24126816", "http://www.ncbi.nlm.nih.gov/pubmed/26367078", "http://www.ncbi.nlm.nih.gov/pubmed/18702959", "http://www.ncbi.nlm.nih.gov/pubmed/18198355", "http://www.ncbi.nlm.nih.gov/pubmed/25210844", "http://www.ncbi.nlm.nih.gov/pubmed/20154362", "http://www.ncbi.nlm.nih.gov/pubmed/19661960", "http://www.ncbi.nlm.nih.gov/pubmed/26176546", "http://www.ncbi.nlm.nih.gov/pubmed/25418138", "http://www.ncbi.nlm.nih.gov/pubmed/26099526", "http://www.ncbi.nlm.nih.gov/pubmed/25477509", "http://www.ncbi.nlm.nih.gov/pubmed/24742676", "http://www.ncbi.nlm.nih.gov/pubmed/26733203", "http://www.ncbi.nlm.nih.gov/pubmed/24065549", "http://www.ncbi.nlm.nih.gov/pubmed/24627478", "http://www.ncbi.nlm.nih.gov/pubmed/27062372", "http://www.ncbi.nlm.nih.gov/pubmed/20190390", "http://www.ncbi.nlm.nih.gov/pubmed/17884815", "http://www.ncbi.nlm.nih.gov/pubmed/23220584" ], "ideal_answer": [ "The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage. CIDEC is highly expressed in adipocytes, but undetectable in normal liver. However, its hepatic expression rises during fasting or under genetic or diet-induced hepatosteatosis in patients." ], "type": "summary", "id": "58ca746d02b8c6095300002d", "snippets": [ { "offsetInBeginSection": 976, "offsetInEndSection": 1170, "text": "The expression levels of related adipocyte markers (PPAR\u03b3, C/EBP\u03b1), mature white adipose tissue specific markers (Cidec, RIP140) increased at the presence of NPY (10(-7), 10(-9), 10(-11) mol/L).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927378", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 458, "text": "The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC; also known in rodents as FSP27 or fat-specific protein 27) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage. CIDEC/Fsp27 is highly expressed in adipose tissue, but undetectable in normal liver. However, its hepatic expression rises during fasting or under genetic or diet-induced hepatosteatosis in both mice and patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25418138", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1363, "text": " Our results also suggest that patients taking fibrates likely have elevated levels of hepatic CIDEC, which may limit the efficient mobilization and catabolism of hepatic TAGs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25418138", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 365, "text": "Fat-specific protein 27 (FSP27, CIDEC in humans) is a lipid-coating protein highly expressed in mature white adipocytes that contributes to unilocular lipid droplet formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25477509", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 460, "text": "We studied mouse models and human tissues to identify molecules associated with ASH progression and focused on the mouse fat-specific protein 27 (FSP-27)/human cell death-inducing DFF45-like effector C (CIDEC) protein, which is expressed in white adipose tissues and promotes formation of fat droplets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26099526", "endSection": "abstract" }, { "offsetInBeginSection": 2073, "offsetInEndSection": 2230, "text": "Hepatic CIDEC mRNA expression was increased in patients with AH and correlated with the degree of hepatic steatosis and disease severity including mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26099526", "endSection": "abstract" }, { "offsetInBeginSection": 2382, "offsetInEndSection": 2580, "text": "Hepatic expression of FSP27/CIDEC is highly up-regulated in mice following chronic-plus-binge ethanol feeding and in patients with AH; this up-regulation contributes to alcohol-induced liver damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26099526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "FSP27 [cell death-inducing DFFA-like effector c (CIDEC) in humans] is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it is overexpressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23220584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23220584", "endSection": "title" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1393, "text": "Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference. Our data indicate that there is a kinetic mechanism of autoregulation between short- and long-term fasting, by which free FAs delivered to the liver during early fasting are accumulated/exported by FSP27/CIDEC, whereas over longer periods of fasting, they are degraded in the mitochondria through the carnitine palmitoyl transferase system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23220584", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 956, "text": "However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26176546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Cell death-inducing DFFA-like effector c (CIDEC) protein, also known as fat specific protein 27 (Fsp27), is localized to lipid droplets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065549", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 440, "text": "We studied mouse models and human tissues to identify molecules associated with ASH progression and focused on the mouse fat-specific protein 27 (FSP-27)/human cell death-inducing DFF45-like effector C (CIDEC) protein, which is expressed in white adipose tissues and promotes formation of fat droplets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26099526", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1280, "text": "Interestingly, in adipose tissue Cidea protein expression was significantly related to body weight (R=.725), epididymal adipose tissue (EWAT) mass (R=.475) and insulin resistance (R=.706), whereas Cidec protein expression was inversely related to body weight (R=-.787), EWAT mass (R=-.706), and insulin resistance (R=-.679).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26176546", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1626, "text": "Similar to adipose tissue, Cidea protein expression in liver was significantly related to body weight (R=.660), EWAT mass (R=.468), and insulin resistance (R=.599); however, unlike adipose tissue, Cidec protein levels in liver were not related to body weight or EWAT mass and only moderately associated with insulin resistance (R=-.422, P=0.051).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26176546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The CIDEC protein is located in lipid droplets (LDs) and the endoplasmic reticulum (ER) and is induced in fat deposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25255829", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 302, "text": "CIDEC protein is required for unilocular lipid droplet formation and optimal energy storage in addition to controlling lipid metabolism in adipocytes and hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065549", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1052, "text": "Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23220584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The hepatic expression of the cell death-inducing DNA fragmentation factor A-like effector family (CIDEA, CIDEB, and CIDEC) genes is markedly upregulated in mouse models of obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661960", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 413, "text": "After the differentiation of adipocyte, the expression pattern of Cidec was similar to that of PPARgamma2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18845124", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 861, "text": "This paper examined the tissue expression profile of CIDEC gene in cattle using real-time RT-PCR to suggest that bovine CIDEC is highly expressed in adipose tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Human adipocytes express high levels of two distinct lipid droplet proteins, fat specific protein 27 (FSP27; also called CIDEC), a member of the CIDE family, and perilipin1 (PLIN1), a member of the PAT family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23399566", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1481, "text": "These results suggest that insulin regulates CIDEA and CIDEC expression via PI3K, and it regulates expression of each protein via Akt1/2- and JNK2-dependent pathways, respectively, in human adipocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21636835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21636835", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20154362", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Human adipocytes express high levels of two distinct lipid droplet proteins, fat specific protein 27 (FSP27; also called CIDEC), a member of the CIDE family, and perilipin1 (PLIN1), a member of the PAT family. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23399566", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 366, "text": "Fat-specific protein 27 (FSP27, CIDEC in humans) is a lipid-coating protein highly expressed in mature white adipocytes that contributes to unilocular lipid droplet formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25477509", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1376, "text": "Using human primary pre-adipocytes, we confirmed that the expression of CIDEC was elevated during the differentiation of pre-adipocytes, and knockdown of CIDEC in human primary pre-adipocytes resulted in differentiation defects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20945533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Cell death-inducing DFF45-like effector C (CIDEC) is a lipid droplet-coating protein that promotes triglyceride accumulation and inhibits lipolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27062372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC; also known in rodents as FSP27 or fat-specific protein 27) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25418138", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 678, "text": "Here we demonstrate that knockdown of the lipid droplet protein FSP27 (a.k.a. CIDEC) in human adipocytes increases expression of ATGL at the level of transcription, whereas overexpression of FSP27 has the opposite effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24742676", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 209, "text": "However, the transcriptional regulation of Cidec in adipocyte remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18845124", "endSection": "abstract" }, { "offsetInBeginSection": 889, "offsetInEndSection": 970, "text": "Moreover, the hepatic expression of CIDEC is downregulated by marked weight loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661960", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 888, "text": "These data demonstrate that, consistent with previous studies conducted in rodents, hepatic expression of CIDEA and CIDEC, but not CIDEB, is increased in obese humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19661960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Transcriptional activation of Cidec by PPARgamma2 in adipocyte.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18845124", "endSection": "title" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1112, "text": "Our data indicated additional fatty acids stimulated hepatic CIDEC expression and an increasing level of CIDEC induced hepatic LD fusion and lipid accumulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25255829", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 441, "text": "We studied mouse models and human tissues to identify molecules associated with ASH progression and focused on the mouse fat-specific protein 27 (FSP-27)/human cell death-inducing DFF45-like effector C (CIDEC) protein, which is expressed in white adipose tissues and promotes formation of fat droplets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26099526", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 622, "text": "By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18702959", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 316, "text": "CIDEC/Fsp27 is highly expressed in adipose tissue, but undetectable in normal liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25418138", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 839, "text": "Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26770990", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 962, "text": "However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26176546", "endSection": "abstract" } ] }, { "body": "Which is the relation between coffee consumption and stroke risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24326448" ], "ideal_answer": [ "The coffee paradox in stroke: Increased consumption linked with fewer strokes." ], "exact_answer": [ "The coffee paradox in stroke: Increased consumption linked with fewer strokes." ], "type": "factoid", "id": "58ce363b02b8c60953000046", "snippets": [ { "offsetInBeginSection": 450, "offsetInEndSection": 854, "text": "The majority of prospective studies have reported a weak inverse association between moderate consumption of coffee and risk of stroke. However, there are yet no clear biological mechanisms whereby coffee might provide cardiovascular health benefits. Awaiting the results from further long-term RCTs and prospective studies, moderate consumption of filtered coffee, tea, and dark chocolate seems prudent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24326448", "endSection": "abstract" } ] }, { "body": "What is the purpose of the Orpington Prognostic Scale?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17903924", "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "http://www.ncbi.nlm.nih.gov/pubmed/11300243", "http://www.ncbi.nlm.nih.gov/pubmed/15595254", "http://www.ncbi.nlm.nih.gov/pubmed/16418057", "http://www.ncbi.nlm.nih.gov/pubmed/16634344", "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "http://www.ncbi.nlm.nih.gov/pubmed/15083439", "http://www.ncbi.nlm.nih.gov/pubmed/19785245", "http://www.ncbi.nlm.nih.gov/pubmed/8463526", "http://www.ncbi.nlm.nih.gov/pubmed/9731605", "http://www.ncbi.nlm.nih.gov/pubmed/12173758", "http://www.ncbi.nlm.nih.gov/pubmed/16337699", "http://www.ncbi.nlm.nih.gov/pubmed/16097508", "http://www.ncbi.nlm.nih.gov/pubmed/12961913" ], "ideal_answer": [ "The Orpington Prognostic Scale (OPS) is used to predict futue functional status of stroke patients, to asses stroke severity, outcome and response to subacute rehabilitation. In patients with stroke, OPS and NIHSS had significant contribution to the estimation of the functional status and OPS was more effective than NIHSS. However, other reported that the OPS has limited predictive accuracy for discharge destination and is a poor predictor of follow-up services." ], "type": "summary", "id": "58861f8b3b87a8a738000003", "snippets": [ { "offsetInBeginSection": 339, "offsetInEndSection": 407, "text": "Stroke severity was determined using the Orpington Prognostic Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16634344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Predicting response to rehabilitation in elderly patients with stroke using the Orpington Prognostic Scale and selected clinical variables.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 315, "text": " The purpose of this study was to determine the ability of the Orpington Prognostic Scale (OPS) to predict outcome and response to subacute rehabilitation in older patients with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1005, "text": "The OPS scores were strong predictors of response to subacute rehabilitation and discharge FIM motor subscale scores. The OPS may warrant a broader application as a prognostic indicator for patients with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "PURPOSE: The aim of our study is to compare the Orpington Prognostic Scale (OPS) and the National Institutes of Health Stroke Scale (NIHSS) and to evaluate whether they help us estimate the future functional status of patients with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Comparison of the Orpington Prognostic Scale (OPS) and the National Institutes of Health Stroke Scale (NIHSS) for the prediction of the functional status of patients with stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "endSection": "title" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1250, "text": "CONCLUSION: In patients with stroke, OPS and NIHSS had significant contribution to the estimation of the functional status and OPS was more effective than NIHSS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 332, "text": "The Orpington Prognostic Score (OPS) is a clinically derived stroke severity scale that can be used to stratify patients into different severity groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16097508", "endSection": "abstract" }, { "offsetInBeginSection": 1539, "offsetInEndSection": 1613, "text": "The OPS is a valid measure of stroke severity in Irish stroke in-patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16097508", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1337, "text": "CONCLUSIONS: Despite high inter-rater and test-retest reliability, the OPS has limited predictive accuracy for discharge destination and is a poor predictor of follow-up services.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16418057", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 536, "text": "PARTICIPANTS: Sixty-four patients with recent stroke admitted for inpatient rehabilitation were randomized within severity strata (Orpington Prognostic Scale) into 1 of 3 intervention groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15083439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Predicting final disposition after stroke using the Orpington Prognostic Score.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15595254", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 374, "text": "In Calgary, the Orpington Prognostic Score (OPS) has been used to predict outcome as an aid to rehabilitation triage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15595254", "endSection": "abstract" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1370, "text": "CONCLUSIONS: The first week OPS can be used to predict final outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15595254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Predicting stroke recovery: three- and six-month rates of patient-centered functional outcomes based on the orpington prognostic scale.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11300243", "endSection": "title" }, { "offsetInBeginSection": 1536, "offsetInEndSection": 1657, "text": "CONCLUSION: OPS scores can predict widely differing rates of functional recovery in five important functional abilities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11300243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Prediction of functional outcome after stroke: comparison of the Orpington Prognostic Scale and the NIH Stroke Scale.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731605", "endSection": "title" }, { "offsetInBeginSection": 1550, "offsetInEndSection": 1806, "text": "CONCLUSIONS: Our results demonstrate that in a sample of mostly mild and moderate strokes, the Orpington Prognostic Scale compared with the NIH Stroke Scale is simpler to use and is a slightly better predictor of ADL and higher levels of physical function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731605", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1631, "text": "CONCLUSIONS: The Orpington score when assessed at 2-weeks post-stroke is a useful prognostic indicator with special suitability for the elderly and may help to select patients most likely to benefit from stroke unit rehabilitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8463526", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1456, "text": "The OPS at 48 hours is a good predictor of outcome at 6 months and 2 years after ischemic stroke and allows early identification of 3 prognostic groups, which may help in identifying patients most likely to benefit from intensive rehabilitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17903924", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 305, "text": "The purpose of this study was to determine the ability of the Orpington Prognostic Scale (OPS) to predict outcome and response to subacute rehabilitation in older patients with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "This study investigates the prognostic ability of the Orpington Prognostic Scale within 48 hours (OPS-1) after admission in predicting outcome at 6 months and 2 years in acute ischemic stroke and compares it with the 2 week OPS (OPS-2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17903924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "The aim of our study is to compare the Orpington Prognostic Scale (OPS) and the National Institutes of Health Stroke Scale (NIHSS) and to evaluate whether they help us estimate the future functional status of patients with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "This study compared the ability of 2 stroke impairment scales, Orpington Prognostic Scale and National Institutes of Health (NIH) Stroke Scale, to predict disability as measured by the Barthel activities of daily living (ADL) Index and higher level of self-reported physical functioning as measured by the SF-36 physical functioning index (PFI) at 1, 3, and 6 months after stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "To provide recovery rates after stroke for specific functions using the Orpington Prognostic Scale (OPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11300243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "To study the validity of the Orpington scale as a predictive instrument of functional prognosis in patients with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12961913", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 373, "text": "In Calgary, the Orpington Prognostic Score (OPS) has been used to predict outcome as an aid to rehabilitation triage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15595254", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 409, "text": "The purpose of this study was to determine the ability of the Orpington Prognostic Scale (OPS) to predict outcome and response to subacute rehabilitation in older patients with stroke.Twenty-two subjects in the subacute care setting diagnosed with acute stroke were prospectively studied", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "This study investigates the prognostic ability of the Orpington Prognostic Scale within 48 hours (OPS-1) after admission in predicting outcome at 6 months and 2 years in acute ischemic stroke and compares it with the 2 week OPS (OPS-2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17903924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Predicting response to rehabilitation in elderly patients with stroke using the Orpington Prognostic Scale and selected clinical variables", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Comparison of the Orpington Prognostic Scale (OPS) and the National Institutes of Health Stroke Scale (NIHSS) for the prediction of the functional status of patients with stroke", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Prediction of functional outcome after stroke: comparison of the Orpington Prognostic Scale and the NIH Stroke Scale", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731605", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 405, "text": "BACKGROUND AND PURPOSE: This study compared the ability of 2 stroke impairment scales, Orpington Prognostic Scale and National Institutes of Health (NIH) Stroke Scale, to predict disability as measured by the Barthel activities of daily living (ADL) Index and higher level of self-reported physical functioning as measured by the SF-36 physical functioning index (PFI) at 1, 3, and 6 months after stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731605", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 316, "text": "The purpose of this study was to determine the ability of the Orpington Prognostic Scale (OPS) to predict outcome and response to subacute rehabilitation in older patients with stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "PURPOSE: The aim of our study is to compare the Orpington Prognostic Scale (OPS) and the National Institutes of Health Stroke Scale (NIHSS) and to evaluate whether they help us estimate the future functional status of patients with stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 410, "text": "The purpose of this study was to determine the ability of the Orpington Prognostic Scale (OPS) to predict outcome and response to subacute rehabilitation in older patients with stroke.Twenty-two subjects in the subacute care setting diagnosed with acute stroke were prospectively studied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 306, "text": "The purpose of this study was to determine the ability of the Orpington Prognostic Scale (OPS) to predict outcome and response to subacute rehabilitation in older patients with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Prediction of functional outcome after stroke: comparison of the Orpington Prognostic Scale and the NIH Stroke Scale.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9731605", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Comparison of the Orpington Prognostic Scale (OPS) and the National Institutes of Health Stroke Scale (NIHSS) for the prediction of the functional status of patients with stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690572", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Predicting response to rehabilitation in elderly patients with stroke using the Orpington Prognostic Scale and selected clinical variables.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16914069", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The Orpington Prognostic Scale within the first 48 hours of admission as a predictor of outcome in ischemic stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17903924", "endSection": "title" } ] }, { "body": "Do IEG create a ripple effect of transcription?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19160492" ], "ideal_answer": [ "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Profiling the primary transcripts in the nucleus with whole-genome tiling arrays delineated simultaneous activation of transcription centred on IEGs.", "rapid induction of immediate-early genes (iegs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes.", "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Even in surrounding intergenic regions, transcriptional activation took place at the same time.", "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes.", "Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci. Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes." ], "exact_answer": "yes", "type": "yesno", "id": "58c276bc02b8c60953000020", "snippets": [ { "offsetInBeginSection": 524, "offsetInEndSection": 676, "text": "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19160492", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 923, "text": "Even in surrounding intergenic regions, transcriptional activation took place at the same time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19160492", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 523, "text": "Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19160492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Ripples from neighbouring transcription.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19160492", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Ripples from neighbouring transcription.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19160492", "endSection": "title" } ] }, { "body": "Which R package is used for the analysis of genome-wide DNA methylation profiles?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23034086" ], "ideal_answer": [ "MethylKit is a comprehensive R package for the analysis of genome-wide DNA methylation profiles. MethylKit includes functions for clustering, sample quality visualization, differential methylation analysis and annotation features, thus automating and simplifying many of the steps for discerning statistically significant bases or regions of DNA methylation." ], "exact_answer": [ "methylKit" ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:1905643", "http://amigo.geneontology.org/amigo/term/GO:1905642", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://amigo.geneontology.org/amigo/term/GO:0044728" ], "type": "factoid", "id": "588f8e9794c1512c50000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034086", "endSection": "title" }, { "offsetInBeginSection": 144, "offsetInEndSection": 592, "text": " Here, we describe an R package, methylKit, that rapidly analyzes genome-wide cytosine epigenetic profiles from high-throughput methylation and hydroxymethylation sequencing experiments. methylKit includes functions for clustering, sample quality visualization, differential methylation analysis and annotation features, thus automating and simplifying many of the steps for discerning statistically significant bases or regions of DNA methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034086", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 330, "text": "Here, we describe an R package, methylKit, that rapidly analyzes genome-wide cytosine epigenetic profiles from high-throughput methylation and hydroxymethylation sequencing experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034086", "endSection": "title" }, { "offsetInBeginSection": 145, "offsetInEndSection": 591, "text": "Here, we describe an R package, methylKit, that rapidly analyzes genome-wide cytosine epigenetic profiles from high-throughput methylation and hydroxymethylation sequencing experiments. methylKit includes functions for clustering, sample quality visualization, differential methylation analysis and annotation features, thus automating and simplifying many of the steps for discerning statistically significant bases or regions of DNA methylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034086", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 592, "text": "Here, we describe an R package, methylKit, that rapidly analyzes genome-wide cytosine epigenetic profiles from high-throughput methylation and hydroxymethylation sequencing experiments. methylKit includes functions for clustering, sample quality visualization, differential methylation analysis and annotation features, thus automating and simplifying many of the steps for discerning statistically significant bases or regions of DNA methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034086", "endSection": "title" } ] }, { "body": "Do T-Cells regulate neuropathic pain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27646435", "http://www.ncbi.nlm.nih.gov/pubmed/22789131", "http://www.ncbi.nlm.nih.gov/pubmed/25787078", "http://www.ncbi.nlm.nih.gov/pubmed/24553941", "http://www.ncbi.nlm.nih.gov/pubmed/25608762", "http://www.ncbi.nlm.nih.gov/pubmed/23747724", "http://www.ncbi.nlm.nih.gov/pubmed/15541898", "http://www.ncbi.nlm.nih.gov/pubmed/22189457" ], "ideal_answer": [ "Macrophage-T cell interactions can mediate neuropathic pain through the glucocorticoid-induced TNF" ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013601", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050378", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010146" ], "type": "yesno", "id": "58c0825502b8c6095300001b", "snippets": [ { "offsetInBeginSection": 346, "offsetInEndSection": 501, "text": "here is evidence for a considerable impact of the immune system also in neuropathic pain. However, the role of the adaptive immune system is still unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25608762", "endSection": "abstract" }, { "offsetInBeginSection": 1806, "offsetInEndSection": 1927, "text": " Our investigation revealed a clear shift of T-cell subsets towards anti-inflammation in patients with neuropathic pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25608762", "endSection": "abstract" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1346, "text": " GITRL expressed on macrophages drives cytokine release and T cell activation, resulting in neuropathic pain via GITR-dependent actions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25787078", "endSection": "abstract" }, { "offsetInBeginSection": 1664, "offsetInEndSection": 1842, "text": "Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain.Copyright \u00a9 2012 International Association for the Study of Pain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22789131", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 211, "text": "Recent studies show that T cells play an important role in neuropathic pain following nerve injury in rats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22189457", "endSection": "abstract" }, { "offsetInBeginSection": 1409, "offsetInEndSection": 1558, "text": "These results show a peripheral pivotal role of CatS in the development of neuropathic pain through the antigen-specific activation of CD4(+) T-cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553941", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 619, "text": "Chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, has been shown to play an important role in neuropathic pain induced by nerve injury and is also produced in various cell types in the CNS, especially in dorsal root ganglia (DRG)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23747724", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 640, "text": "In the present study, we investigated systemic T-cell subset responses and T-cell related cytokine profiles in patients with chronic neuropathic pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25608762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Anti-inflammatory T-cell shift in neuropathic pain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25608762", "endSection": "title" }, { "offsetInBeginSection": 1664, "offsetInEndSection": 1757, "text": "Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22789131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22789131", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25787078", "endSection": "title" } ] }, { "body": "What is the incidence of new cases of X-linked adrenoleukodystrophy (ALD) in Australian and New Zealand in the late 1990's?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9556302" ], "ideal_answer": [ "cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. ", "cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000.", "When looking cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996, it was estimated that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000." ], "exact_answer": [ "1.6 per 100,000 people" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000326", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009520", "http://www.disease-ontology.org/api/metadata/DOID:10588" ], "type": "factoid", "id": "58cc5bae02b8c60953000037", "snippets": [ { "offsetInBeginSection": 453, "offsetInEndSection": 655, "text": "cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9556302", "endSection": "abstract" } ] }, { "body": "Can telomere length shortening be reversed by telomerase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27401551", "http://www.ncbi.nlm.nih.gov/pubmed/27483324", "http://www.ncbi.nlm.nih.gov/pubmed/26903545", "http://www.ncbi.nlm.nih.gov/pubmed/27154402", "http://www.ncbi.nlm.nih.gov/pubmed/27029895" ], "ideal_answer": [ "Yes, telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia." ], "exact_answer": "yes", "type": "yesno", "id": "58cd675c02b8c6095300003b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Telomere length is regulated around an equilibrium set point. Telomeres shorten during replication and are lengthened by telomerase. Disruption of the length equilibrium leads to disease; thus, it is important to understand the mechanisms that regulate length at the molecular level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27401551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 455, "text": "High telomerase activity is detected in nearly all human cancers but most human cells are devoid of telomerase activity. There is well-documented evidence that reactivation of telomerase occurs during cellular transformation. In humans, tumors can rely in reactivation of telomerase or originate in a telomerase positive stem/progenitor cell, or rely in alternative lengthening of telomeres, a telomerase-independent telomere-length maintenance mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27483324", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1247, "text": " Together, these observations may provoke a re-evaluation of telomere and telomerase based therapies, both in telomerase inhibition for cancer therapy and telomerase activation for tissue regeneration and anti-ageing strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27483324", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 253, "text": "Telomeres progressively shorten throughout life. A hallmark of advanced malignancies is the ability for continuous cell divisions that almost universally correlates with the stabilization of telomere length by the reactivation of telomerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27029895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Telomerase-mediated telomere elongation provides cell populations with the ability to proliferate indefinitely. Telomerase is capable of recognizing and extending the shortest telomeres in cells;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27154402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26903545", "endSection": "title" } ] }, { "body": "Is ABCE1 involved in ribosomal recycling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27824037", "http://www.ncbi.nlm.nih.gov/pubmed/26276635", "http://www.ncbi.nlm.nih.gov/pubmed/25001285", "http://www.ncbi.nlm.nih.gov/pubmed/25659154", "http://www.ncbi.nlm.nih.gov/pubmed/25128630" ], "ideal_answer": [ "Yes, recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea" ], "exact_answer": "yes", "type": "yesno", "id": "58ce5a1602b8c60953000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Ribosome recycling orchestrated by the ATP binding cassette (ABC) protein ABCE1 can be considered as the final-or the first-step within the cyclic process of protein synthesis, connecting translation termination and mRNA surveillance with re-initiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824037", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 260, "text": " Recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25659154", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 560, "text": "d a termination/prerecycling complex containing eRF1-ABCE1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25001285", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 698, "text": "ABCE1, a eukaryotic ribosome recycling factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25128630", "endSection": "abstract" } ] }, { "body": "What are clinical features of the de Morsier syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9606688", "http://www.ncbi.nlm.nih.gov/pubmed/20602044", "http://www.ncbi.nlm.nih.gov/pubmed/24379556", "http://www.ncbi.nlm.nih.gov/pubmed/3625236", "http://www.ncbi.nlm.nih.gov/pubmed/12373677", "http://www.ncbi.nlm.nih.gov/pubmed/20049400", "http://www.ncbi.nlm.nih.gov/pubmed/18018427", "http://www.ncbi.nlm.nih.gov/pubmed/10037251", "http://www.ncbi.nlm.nih.gov/pubmed/23422579", "http://www.ncbi.nlm.nih.gov/pubmed/24678945", "http://www.ncbi.nlm.nih.gov/pubmed/308321", "http://www.ncbi.nlm.nih.gov/pubmed/26842535", "http://www.ncbi.nlm.nih.gov/pubmed/23233151", "http://www.ncbi.nlm.nih.gov/pubmed/19270460", "http://www.ncbi.nlm.nih.gov/pubmed/22330852", "http://www.ncbi.nlm.nih.gov/pubmed/10951302", "http://www.ncbi.nlm.nih.gov/pubmed/17876417", "http://www.ncbi.nlm.nih.gov/pubmed/27136085", "http://www.ncbi.nlm.nih.gov/pubmed/6475068", "http://www.ncbi.nlm.nih.gov/pubmed/12733175" ], "ideal_answer": [ "Classic triad of the De Morsier syndrome (septooptic dysplasia) includes optic nerve hypoplasia, the absence of septum pellucidum, and pituitary hypoplasia." ], "exact_answer": [ [ "optic nerve hypoplasia" ], [ "absence of septum pellucidum" ], [ "pituitary hypoplasia" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "list", "id": "588f952994c1512c50000007", "snippets": [ { "offsetInBeginSection": 76, "offsetInEndSection": 228, "text": " SOD was formerly known as de Morsier syndrome, which associated a midline brain defect such as an absent septum pellucidum with optic nerve hypoplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26842535", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 506, "text": "The triad consists of optic nerve hypoplasia, pituitary hormone abnormalities, and midline brain defects, although it can vary in the severity of clinical presentation and phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26842535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "INTRODUCTION: Previous studies have described septooptic dysplasia (SOD) to describe patients who have optic nerve hypoplasia, the absence of septum pellucidum, and pituitary hypoplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27136085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "BACKGROUND: Septo-optic dysplasia, also referred to as de Morsier syndrome, is a congenital condition characterized by classic triad features: midline brain abnormalities, optic nerve hypoplasia and pituitary endocrine dysfunction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Septo-optic dysplasia (SOD), otherwise called De Morsier syndrome, is a developmental anomaly of mid-line brain structures and includes optic nerve hypoplasia, absence of the septum pellucidum and hypothalamo-pituitary abnormalities). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23422579", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 261, "text": "The frequently associated features of hypopituitarism and absent septum pellucidum were felt to have embryonic linkage as \"septo-optic dysplasia\" or \"de Morsier's syndrome.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23233151", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 269, "text": "An MRI of the brain demonstrated the absence of the septum pellucidum, which confirmed a diagnosis of septo-optic dysplasia or de Morsier syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18018427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Septo-optic dysplasia (De Morsier syndrome) is a developmental anomaly of mid-line brain structures and includes optic nerve hypoplasia, absence of the septum pellucidum and hypothalamo-pituitary abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10037251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Septo-optic dysplasia, also known as de Morsier syndrome, is a rare congenital entity almost always characterized by hypoplasia/dysplasia of the optical nerve, chiasma or optic radiations and the complete or partial absence of the septum pellucidum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The de Morsier syndrome, or septo-optic dysplasia, is a developmental anomaly characterized by involvement of the optic system, hypothalamic-pituitary axis and septum pellucidum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3625236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The term septooptic dysplasia was coined in 1956 by de Morsier, who pointed out the association of optic nerve hypoplasia and absence of the septum pellucidum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12733175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Septo-optic dysplasia, also referred to as de Morsier syndrome, is a congenital condition characterized by classic triad features: midline brain abnormalities, optic nerve hypoplasia and pituitary endocrine dysfunction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Septo-optic dysplasia (SOD), also referred to as de Morsier syndrome, is a rare congenital condition, characterized by two of the classic triad features: midline brain abnormalities, optic nerve hypoplasia (ONH) and pituitary endocrine dysfunction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Septo-optic dysplasia (SOD), also referred to as de Morsier syndrome, is a rare congenital condition, characterized by two of the classic triad features: midline brain abnormalities, optic nerve hypoplasia (ONH) and pituitary endocrine dysfunction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Septo-optic dysplasia, also referred to as de Morsier syndrome, is a congenital condition characterized by classic triad features: midline brain abnormalities, optic nerve hypoplasia and pituitary endocrine dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Septo-optic dysplasia (SOD), also referred to as de Morsier syndrome, is a rare congenital condition, characterized by two of the classic triad features: midline brain abnormalities, optic nerve hypoplasia (ONH) and pituitary endocrine dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "[Optic nerve hypoplasia and growth hormone deficiency: de Morsier's syndrome].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6475068", "endSection": "title" } ] }, { "body": "Does oculocutaneous albinism show an autosomal recessive inheritance?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22088535", "http://www.ncbi.nlm.nih.gov/pubmed/14599068", "http://www.ncbi.nlm.nih.gov/pubmed/8190479", "http://www.ncbi.nlm.nih.gov/pubmed/20019752", "http://www.ncbi.nlm.nih.gov/pubmed/17768386", "http://www.ncbi.nlm.nih.gov/pubmed/12829739", "http://www.ncbi.nlm.nih.gov/pubmed/8618053", "http://www.ncbi.nlm.nih.gov/pubmed/25703744", "http://www.ncbi.nlm.nih.gov/pubmed/24054038", "http://www.ncbi.nlm.nih.gov/pubmed/16752321", "http://www.ncbi.nlm.nih.gov/pubmed/23112997", "http://www.ncbi.nlm.nih.gov/pubmed/22817390", "http://www.ncbi.nlm.nih.gov/pubmed/8302318", "http://www.ncbi.nlm.nih.gov/pubmed/10960773", "http://www.ncbi.nlm.nih.gov/pubmed/26165494", "http://www.ncbi.nlm.nih.gov/pubmed/8042664", "http://www.ncbi.nlm.nih.gov/pubmed/19208379", "http://www.ncbi.nlm.nih.gov/pubmed/12727022", "http://www.ncbi.nlm.nih.gov/pubmed/11045591", "http://www.ncbi.nlm.nih.gov/pubmed/17355913", "http://www.ncbi.nlm.nih.gov/pubmed/7064008", "http://www.ncbi.nlm.nih.gov/pubmed/25919014", "http://www.ncbi.nlm.nih.gov/pubmed/16868655", "http://www.ncbi.nlm.nih.gov/pubmed/3742854" ], "ideal_answer": [ "Yes, oculocutaneous albinism shows an autosomal recessive inheritance." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050632", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016115", "http://www.disease-ontology.org/api/metadata/DOID:0050737", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000417" ], "type": "yesno", "id": "58cbb55402b8c60953000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypopigmentation in eyes, hair and skin, accompanied with vision loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26165494", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 152, "text": "Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22817390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Oculocutaneous albinism type 2 (OCA2) is a human autosomal-recessive hypopigmentation disorder associated with pathological mutations of the OCA2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019752", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 186, "text": "Oculocutaneous albinism type1 (OCA1) is characterized by the absence of melanin pigmentation. The mutation on TYR gene makes OCA1 as an autosomal recessive genetic disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23112997", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 953, "text": "Our patients were diagnosed as affected with Oculocutaneous albinism type1a. Analysis of pedigree pattern showed an autosomal recessive inheritance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23112997", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 174, "text": "Oculocutaneous albinism (OCA) is an autosomal recessive disorder of melanin biosynthesis that results in congenital hypopigmentation of ocular and cutaneous tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17768386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Oculocutaneous albinism is an autosomal recessive genetic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10960773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Melanin biosynthesis is reduced in oculocutaneous albinism, an autosomal recessive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24054038", "endSection": "abstract" }, { "offsetInBeginSection": 1384, "offsetInEndSection": 1554, "text": "The pedigrees were consistent with an autosomal recessive inheritance pattern.CONCLUSION: This unique type of oculocutaneous albinism has heterogeneous clinical features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8190479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22817390", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 522, "text": "The Q402 allele has been associated with autosomal recessive ocular albinism when it is in trans with a tyrosinase gene mutation associated with oculocutaneous albinism type 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19208379", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 301, "text": "Analysis using the POINTER program showed that this type of oculocutaneous albinism was inherited in an autosomal recessive pattern, with an estimated gene frequency of 0.025 +/- 0.007 in this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3742854", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 815, "text": "We have identified 12 families with oculocutaneous albinism type 1 that exhibit segregation of the c.1205G>A variant with a known pathologic mutation on the homologous chromosome, and demonstrate no genetic association between autosomal recessive oculocutaneous albinism and the Q402 variant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19208379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND: Type II (tyrosinase-positive) oculocutaneous albinism is an autosomal recessive disorder that has recently been mapped to chromosome segment 15q11-q13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8302318", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1735, "text": "The child with ocular albinism was heterozygous for two different mutations in the P gene.CONCLUSIONS: Abnormalities of the P gene are associated with a wide range of clinical phenotypes, including type II oculocutaneous albinism, albinism associated with the Prader-Willi syndrome, and at least some cases of autosomal recessive ocular albinism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8302318", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 768, "text": "Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17355913", "endSection": "abstract" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1514, "text": "The pedigrees were consistent with an autosomal recessive inheritance pattern.This unique type of oculocutaneous albinism has heterogeneous clinical features", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8190479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Oculocutaneous albinism (OCA) is an autosomal recessive disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25919014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Oculocutaneous albinism (OCA) is an autosomal recessive disorder of abnormal melanin formation, which results in hypopigmentation of skin, hair and eyes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25703744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The mutation of the tyrosinase (TYR) gene results in oculocutaneous albinism type 1 (OCA1), an autosomal recessive genetic disorder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088535", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 690, "text": "We found oculo-cutaneous albinism in two brothers and granular dystrophy in three brothers, the mother and a son.Corneal dystrophy is an autosomal dominant disorder inherited independently of oculocutaneous albinism, which is inherited as an autosomal recessive condition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16752321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Oculocutaneous albinism (OCA) type 4 is a newly identified human autosomal recessive hypopigmentary disorder that disrupts pigmentation in the skin, hair and eyes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12829739", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 302, "text": "Analysis using the POINTER program showed that this type of oculocutaneous albinism was inherited in an autosomal recessive pattern, with an estimated gene frequency of 0.025 +/- 0.007 in this population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3742854", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 720, "text": "DISCUSSION: Corneal dystrophy is an autosomal dominant disorder inherited independently of oculocutaneous albinism, which is inherited as an autosomal recessive condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16752321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Oculocutaneous albinism type II (OCA2) is an autosomal recessively inherited disorder, characterized by white hair and skin, and loss of pigment in the eyes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12727022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Is autosomal recessive deafness associated with oculocutaneous albinism a \"coincidence syndrome\"?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16868655", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Oculocutaneous albinism, immunodeficiency, hematological disorders, and minor anomalies: a new autosomal recessive syndrome?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8042664", "endSection": "title" }, { "offsetInBeginSection": 583, "offsetInEndSection": 769, "text": "Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17355913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypopigmentation in eyes, hair and skin, accompanied with vision loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26165494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22817390", "endSection": "abstract" } ] }, { "body": "Which is the largest metabolic gene cluster in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15951822", "http://www.ncbi.nlm.nih.gov/pubmed/22916115" ], "ideal_answer": [ "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source.", "the dal cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable saccharomyces cerevisiae to use allantoin as a nitrogen source.", "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source. The DAL cluster is located in a domain of modified chromatin involving both H2A.Z histone exchange and Hst1-Sum1-mediated histone deacetylation, and it may be a coadapted gene complex formed by epistatic selection.", "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source. Six of the eight genes involved in allantoin degradation, which were previously scattered around the genome, became relocated to a single subtelomeric site in an ancestor of S. cerevisiae and Saccharomyces castellii." ], "exact_answer": [ "The DAL cluster" ], "type": "factoid", "id": "58d0dc878acda34529000004", "snippets": [ { "offsetInBeginSection": 217, "offsetInEndSection": 408, "text": "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951822", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 406, "text": "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Birth of a metabolic gene cluster in yeast by adaptive gene relocation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951822", "endSection": "title" }, { "offsetInBeginSection": 217, "offsetInEndSection": 407, "text": "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Birth of a metabolic gene cluster in yeast by adaptive gene relocation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951822", "endSection": "title" }, { "offsetInBeginSection": 217, "offsetInEndSection": 409, "text": "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15951822", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 488, "text": "For example the DAL metabolic cluster in yeast was assembled in recent evolutionary times in the Hemiascomycetes lineage, through a set of rearrangements that brought together the genes involved in the allantoin degradation pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22916115", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 487, "text": "For example the DAL metabolic cluster in yeast was assembled in recent evolutionary times in the Hemiascomycetes lineage, through a set of rearrangements that brought together the genes involved in the allantoin degradation pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22916115", "endSection": "abstract" } ] }, { "body": "What is the applicability of the MCAST algorithm?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16253142", "http://www.ncbi.nlm.nih.gov/pubmed/14534166", "http://www.ncbi.nlm.nih.gov/pubmed/26704599" ], "ideal_answer": [ "The MCAST algorithm uses a hidden Markov model with a P-value-based scoring scheme to identify candidate CRMs." ], "type": "summary", "id": "5895f75aad49cff847000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "MCAST: scanning for cis-regulatory motif clusters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26704599", "endSection": "title" }, { "offsetInBeginSection": 577, "offsetInEndSection": 1340, "text": " The MCAST algorithm uses a hidden Markov model with a P-value-based scoring scheme to identify candidate CRMs. Here, we introduce a new version of MCAST that offers improved graphical output, a dynamic background model, statistical confidence estimates based on false discovery rate estimation and, most significantly, the ability to predict CRMs while taking into account epigenomic data such as DNase I sensitivity or histone modification data. We demonstrate the validity of MCAST's statistical confidence estimates and the utility of epigenomic priors in identifying CRMs.AVAILABILITY AND IMPLEMENTATION: MCAST is part of the MEME Suite software toolkit. A web server and source code are available at http://meme-suite.org and http://alternate.meme-suite.org", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26704599", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 857, "text": "On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16253142", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1385, "text": "The p-value scoring also allows mcast to only accept motif occurrences with significance below a user-specified threshold, while still assigning better scores to motif occurrences with lower p-values. mcast can search long DNA sequences, modeling length distributions between motifs within a regulatory module, but ignoring length distributions between modules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14534166", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 667, "text": "Given a collection of known transcription factor binding motifs, many bioinformatics methods have been proposed over the past 15 years for identifying within a genomic sequence candidate CRMs consisting of clusters of those motifs.The MCAST algorithm uses a hidden Markov model with a P-value-based scoring scheme to identify candidate CRMs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26704599", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 853, "text": "The algorithm, called mcast, takes as input a DNA database and a collection of binding site motifs that are known to operate in concert. mcast uses a motif-based hidden Markov model with several novel features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14534166", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 780, "text": "The algorithm, called mcast, takes as input a DNA database and a collection of binding site motifs that are known to operate in concert.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14534166", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 835, "text": "On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16253142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "MCAST: scanning for cis-regulatory motif clusters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26704599", "endSection": "title" } ] }, { "body": "Which ApoE isoform is associated with atherosclerosis and Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15014128", "http://www.ncbi.nlm.nih.gov/pubmed/16903824", "http://www.ncbi.nlm.nih.gov/pubmed/14614898", "http://www.ncbi.nlm.nih.gov/pubmed/18823563", "http://www.ncbi.nlm.nih.gov/pubmed/15570172", "http://www.ncbi.nlm.nih.gov/pubmed/24633805", "http://www.ncbi.nlm.nih.gov/pubmed/27683909", "http://www.ncbi.nlm.nih.gov/pubmed/15475580", "http://www.ncbi.nlm.nih.gov/pubmed/22918225", "http://www.ncbi.nlm.nih.gov/pubmed/25871773", "http://www.ncbi.nlm.nih.gov/pubmed/10816430", "http://www.ncbi.nlm.nih.gov/pubmed/7846048", "http://www.ncbi.nlm.nih.gov/pubmed/21705182", "http://www.ncbi.nlm.nih.gov/pubmed/22401921", "http://www.ncbi.nlm.nih.gov/pubmed/16540478", "http://www.ncbi.nlm.nih.gov/pubmed/21907569", "http://www.ncbi.nlm.nih.gov/pubmed/8726460", "http://www.ncbi.nlm.nih.gov/pubmed/10949525", "http://www.ncbi.nlm.nih.gov/pubmed/22393530", "http://www.ncbi.nlm.nih.gov/pubmed/26427386", "http://www.ncbi.nlm.nih.gov/pubmed/15649697", "http://www.ncbi.nlm.nih.gov/pubmed/11701639", "http://www.ncbi.nlm.nih.gov/pubmed/18359298", "http://www.ncbi.nlm.nih.gov/pubmed/24754513", "http://www.ncbi.nlm.nih.gov/pubmed/23293020", "http://www.ncbi.nlm.nih.gov/pubmed/8782820", "http://www.ncbi.nlm.nih.gov/pubmed/20531185", "http://www.ncbi.nlm.nih.gov/pubmed/8367470", "http://www.ncbi.nlm.nih.gov/pubmed/7891887", "http://www.ncbi.nlm.nih.gov/pubmed/23781009", "http://www.ncbi.nlm.nih.gov/pubmed/19033669", "http://www.ncbi.nlm.nih.gov/pubmed/19549280" ], "ideal_answer": [ "The ApoE4 isoform is associated with increased frequency of atherosclerosis and Alzheimer's disease (AD)." ], "exact_answer": [ "ApoE4 isoform", "Apolipoprotein E4 isoform" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544", "http://www.disease-ontology.org/api/metadata/DOID:10652", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050197", "http://www.disease-ontology.org/api/metadata/DOID:1936", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053327" ], "type": "factoid", "id": "58b6cd3222d300530900000d", "snippets": [ { "offsetInBeginSection": 206, "offsetInEndSection": 334, "text": "Among three isoforms, the apoE4 isoform is associated with increased frequency of atherosclerosis and Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16903824", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 589, "text": "Homozygosity for ApoE epsilon4 is associated with atherosclerosis and Alzheimer's disease whereas ApoE epsilon2 and epsilon3 tend to be protective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18823563", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 715, "text": "Importantly, lipoproteins containing the apoE3 isoform had higher TGF-beta levels and bioactivity than those containing apoE4, a major genetic risk factor for atherosclerosis and Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549280", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 332, "text": "ApoE4 is positively associated with atherosclerosis and late-onset and sporadic Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15475580", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 1176, "text": "Isoform (allele)-specific effects include the association of apoE2 with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis and the association of apoE4 with increased risk for both atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth; isoform-specific differences in cellular signaling events may also exist. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11701639", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 187, "text": "Although APOE-epsilon3 is considered a longevity gene, APOE-epsilon4 is a dual risk factor to atherosclerosis and Alzheimer disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "The apolipoprotein E (apoE) type epsilon 4 isoform specifies increased cerebral and cerebrovascular accumulation of amyloid-beta protein (A beta) and contributes to the genetic susceptibility underlying a large proportion (approximately 60%) of typical, sporadic Alzheimer disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8726460", "endSection": "abstract" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1504, "text": "The structural preference of apoE4 to remain functional in solution may explain the enhanced opportunity of apoE4 isoform to display its pathophysiologic functions in atherosclerosis and Alzheimer disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The apolipoprotein E (APOE) E4 allele is associated with Alzheimer's disease, cardiovascular disease, and decreased longevity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8782820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The apolipoprotein E type 4 allele is a susceptibility gene for late-onset Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7891887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "The apolipoprotein E (ApoE) \u03b54 allele is the strongest risk factor of sporadic Alzheimers disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE \u03b52, \u03b53, \u03b54) remain controversial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24633805", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 331, "text": "Among three isoforms, the apoE4 isoform is associated with increased frequency of atherosclerosis and Alzheimers disease (AD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16903824", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 574, "text": "Homozygosity for ApoE epsilon4 is associated with atherosclerosis and Alzheimers disease whereas ApoE epsilon2 and epsilon3 tend to be protective", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18823563", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 590, "text": "Homozygosity for ApoE epsilon4 is associated with atherosclerosis and Alzheimer's disease whereas ApoE epsilon2 and epsilon3 tend to be protective. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18823563", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 189, "text": "Although APOE-epsilon3 is considered a longevity gene, APOE-epsilon4 is a dual risk factor to atherosclerosis and Alzheimer disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540478", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 461, "text": "The apoE4 allele is a major risk factor for late-onset familial and sporadic Alzheimer's disease (AD) and is associated with a poor outcome after brain injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14614898", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 333, "text": "Among three isoforms, the apoE4 isoform is associated with increased frequency of atherosclerosis and Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16903824", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 577, "text": "Homozygosity for ApoE epsilon4 is associated with atherosclerosis and Alzheimer's disease whereas ApoE epsilon2 and epsilon3 tend to be protective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18823563", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 714, "text": "Importantly, lipoproteins containing the apoE3 isoform had higher TGF-beta levels and bioactivity than those containing apoE4, a major genetic risk factor for atherosclerosis and Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549280", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 1175, "text": "Isoform (allele)-specific effects include the association of apoE2 with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis and the association of apoE4 with increased risk for both atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth; isoform-specific differences in cellular signaling events may also exist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11701639", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 728, "text": "The decreased antioxidant activity of E4 could contribute to its association with Alzheimer's disease, cardiovascular disease and decreased longevity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8782820", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 647, "text": "The isoform apoE4 is associated with an increased risk of Alzheimer's disease and it has been postulated that high intracellular cholesterol levels promote the amyloidogenic processing of amyloid precursor protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18359298", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 337, "text": "Among three \u025b2, \u025b3, \u025b4 alleles, \u025b4 allele is associated with the increase in cholesterol level, risk of atherosclerosis and Alzheimer disease, while \u025b2 allele is associated with the decrease in cholesterol level and risk of atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21705182", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 188, "text": "Although APOE-epsilon3 is considered a longevity gene, APOE-epsilon4 is a dual risk factor to atherosclerosis and Alzheimer disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540478", "endSection": "abstract" }, { "offsetInBeginSection": 1307, "offsetInEndSection": 1513, "text": "The structural preference of apoE4 to remain functional in solution may explain the enhanced opportunity of apoE4 isoform to display its pathophysiologic functions in atherosclerosis and Alzheimer disease..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16540478", "endSection": "abstract" } ] }, { "body": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "http://www.ncbi.nlm.nih.gov/pubmed/22987666", "http://www.ncbi.nlm.nih.gov/pubmed/18957701", "http://www.ncbi.nlm.nih.gov/pubmed/24349264", "http://www.ncbi.nlm.nih.gov/pubmed/21092253" ], "ideal_answer": [ "ULEs are located in intergenic or intronic regions and are depleted from segmental duplications. In addition, here we show that these elements are preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in duplications), and that this association is not related with a higher content of genes.", "we begin by showing that depletion for uces characterizes the most recent large-scale human cnv datasets and then find that even newly formed de novo cnvs, which have passed through meiosis at most once, are significantly depleted for uces.", "Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell. These elements are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development.", "Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset.", "Here we address the process by which CNVs become depleted of UCEs. We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs.", "Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants." ], "exact_answer": "no", "type": "yesno", "id": "58a71bb960087bc10a00002d", "snippets": [ { "offsetInBeginSection": 227, "offsetInEndSection": 293, "text": "Here we address the process by which CNVs become depleted of UCEs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 534, "text": "We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 680, "text": "In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 954, "text": "Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1045, "text": "ULEs are located in intergenic or intronic regions and are depleted from segmental duplications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22987666", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 579, "text": "Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1341, "text": "In addition, here we show that these elements are preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in duplications), and that this association is not related with a higher content of genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1433, "text": "In contrast, pathogenic CNVs lacking UCEs showed almost a threefold higher content in genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 581, "text": "We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18957701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "title" }, { "offsetInBeginSection": 610, "offsetInEndSection": 936, "text": "Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 714, "text": "Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 578, "text": "We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18957701", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 715, "text": "Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 931, "text": "melanogaster genome revealed depletion of the P-element and piggyBac insertions in and around the Sophophora UCEs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24349264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "title" }, { "offsetInBeginSection": 612, "offsetInEndSection": 717, "text": "Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998490", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 567, "text": "Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21092253", "endSection": "abstract" } ] }, { "body": "What organism causes woolsorter's disease", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18959192", "http://www.ncbi.nlm.nih.gov/pubmed/15486181" ], "ideal_answer": [ "Woolsorter's disease is caused by the same organism as Anthrax, bacillus Anthrax. " ], "exact_answer": [ "Bacillus Anthracis" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:7427", "http://www.disease-ontology.org/api/metadata/DOID:0050160", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009784" ], "type": "factoid", "id": "58caf0be02b8c6095300002f", "snippets": [ { "offsetInBeginSection": 661, "offsetInEndSection": 756, "text": "Today, woolsorters' disease and other industrial manifestations of anthrax are extremely rare, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15486181", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 943, "text": "Working independently of their more famous counterparts (Robert Koch and Louis Pasteur), Anglo-American anthrax investigators used visual representations of anthrax bacilli to persuade their peers that a specific, identifiable cause produced all forms of anthrax-malignant pustule (cutaneous anthrax), intestinal anthrax, and woolsorter's disease (pneumonic anthrax). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18959192", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 913, "text": "Today, woolsorters' disease and other industrial manifestations of anthrax are extremely rare, but the increasing threat of bioterrorism means that the international dread and historical lessons of this significant condition should never be forgotten. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15486181", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 912, "text": "Today, woolsorters' disease and other industrial manifestations of anthrax are extremely rare, but the increasing threat of bioterrorism means that the international dread and historical lessons of this significant condition should never be forgotten.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15486181", "endSection": "abstract" } ] }, { "body": "Which annotated database of A-to-I RNA editing is available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24163250" ], "ideal_answer": [ "RADAR is a rigorously annotated database of A-to-I RNA editing. RADAR includes a comprehensive collection of A-to-I RNA editing sites identified in humans (Homo sapiens), mice (Mus musculus) and flies (Drosophila melanogaster), together with extensive manually curated annotations for each editing site. RADAR also includes an expandable listing of tissue-specific editing levels for each editing site, which will facilitate the assignment of biological functions to specific editing sites.", "The identification of A-to-I RNA editing sites has been dramatically accelerated in the past few years by high-throughput RNA sequencing studies. RADAR includes a comprehensive collection of A-to-I RNA editing sites identified in humans (Homo sapiens), mice (Mus musculus) and flies (Drosophila melanogaster), together with extensive manually curated annotations for each editing site." ], "exact_answer": [ "RADAR" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017393" ], "type": "factoid", "id": "587e1a01fc7e8dd84f000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "RADAR: a rigorously annotated database of A-to-I RNA editing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "We present RADAR--a rigorously annotated database of A-to-I RNA editing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 678, "text": "The identification of A-to-I RNA editing sites has been dramatically accelerated in the past few years by high-throughput RNA sequencing studies. RADAR includes a comprehensive collection of A-to-I RNA editing sites identified in humans (Homo sapiens), mice (Mus musculus) and flies (Drosophila melanogaster), together with extensive manually curated annotations for each editing site. RADAR also includes an expandable listing of tissue-specific editing levels for each editing site, which will facilitate the assignment of biological functions to specific editing sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "We present RADAR--a rigorously annotated database of A-to-I RNA editing (available at http://RNAedit.com).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "RADAR: a rigorously annotated database of A-to-I RNA editing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "We present RADAR--a rigorously annotated database of A-to-I RNA editing (available at http://RNAedit.com). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 493, "text": "RADAR includes a comprehensive collection of A-to-I RNA editing sites identified in humans (Homo sapiens), mice (Mus musculus) and flies (Drosophila melanogaster), together with extensive manually curated annotations for each editing site. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "RADAR: a rigorously annotated database of A-to-I RNA editing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163250", "endSection": "title" } ] }, { "body": "Do normal cells express the protein TERT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21790308", "http://www.ncbi.nlm.nih.gov/pubmed/17531113", "http://www.ncbi.nlm.nih.gov/pubmed/17346111", "http://www.ncbi.nlm.nih.gov/pubmed/18956258" ], "ideal_answer": [ "\u039d\u03bf, telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells. Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity." ], "exact_answer": "no", "type": "yesno", "id": "58cd6d9702b8c6095300003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Since telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells, it has become a very promising target for anti-cancer therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21790308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Telomerase plays a pivotal role in cellular immortality and tumorigenesis. Its activity is normally not detectable in most somatic cells while it is reactivated in the vast majority of cancer cells. Therefore, inhibition of telomerase has been viewed as a promising anticancer approach due to its specificity for cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18956258", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 264, "text": "Telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells. Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17531113", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 890, "text": "elomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346111", "endSection": "abstract" } ] }, { "body": "Which protein complexes recognize centromeric (CEN) DNA in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22693454", "http://www.ncbi.nlm.nih.gov/pubmed/3464952", "http://www.ncbi.nlm.nih.gov/pubmed/23620291" ], "ideal_answer": [ "The Schizosaccharomyces pombe centromere-linked genes, LYS1 and CYH1 on chromosome I and TPS13 and RAN1 on chromosome II, have been isolated. In budding yeast, as well as in other eukaryotes, the Cse4 histone variant (known in vertebrates as CENP-A) is believed to substitute for histone H3 at the centromeric nucleosome.", "The Schizosaccharomyces pombe centromere-linked genes, LYS1 and CYH1 on chromosome I and TPS13 and RAN1 on chromosome II, have been isolated Histone H3 localizes to the centromeric DNA in budding yeast In budding yeast, as well as in other eukaryotes, the Cse4 histone variant (known in vertebrates as CENP-A) is believed to substitute for histone H3 at the centromeric nucleosome", "The Schizosaccharomyces pombe centromere-linked genes, LYS1 and CYH1 on chromosome I and TPS13 and RAN1 on chromosome II, have been isolated" ], "exact_answer": [ [ "Lys1" ], [ "Cyh1" ], [ "Tps13" ], [ "Ran1" ], [ "H3" ], [ "Cse4" ] ], "type": "list", "id": "58a71f7460087bc10a00002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The Schizosaccharomyces pombe centromere-linked genes, LYS1 and CYH1 on chromosome I and TPS13 and RAN1 on chromosome II, have been isolated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3464952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Histone H3 localizes to the centromeric DNA in budding yeast", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693454", "endSection": "title" }, { "offsetInBeginSection": 503, "offsetInEndSection": 682, "text": " In budding yeast, as well as in other eukaryotes, the Cse4 histone variant (known in vertebrates as CENP-A) is believed to substitute for histone H3 at the centromeric nucleosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693454", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1142, "text": "Surprisingly, we observed a strong interaction of H3, as well as Cse4, H4, H2A, and H2B, but not histone chaperone Scm3 (HJURP in human) with the centromeric DNA. H3 localizes to centromeric DNA at all stages of the cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693454", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1325, "text": "Our results favor a H3-Cse4 heterotypic octamer at the budding yeast centromere", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693454", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 257, "text": "In budding yeast, a single right-handed cenH3/H4/H2A/H2B tetramer wraps the \u223c80-bp Centromere DNA Element II (CDE II) sequence of each centromere into a 'hemisome'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23620291", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 559, "text": "Here, we show that Cse4 octamers remain intact under conditions of low salt and urea that dissociate H3 octamers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23620291", "endSection": "abstract" } ] }, { "body": "Is there any involvement of the long non-coding RNA Gomafu in schizophrenia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23628989", "http://www.ncbi.nlm.nih.gov/pubmed/25145264" ], "ideal_answer": [ "Yes. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085", "http://www.disease-ontology.org/api/metadata/DOID:5419", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019967", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012561", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012559" ], "type": "yesno", "id": "588fbedced9bbee70d000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628989", "endSection": "title" }, { "offsetInBeginSection": 308, "offsetInEndSection": 1154, "text": "Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Gomafu/MIAT/Rncr2 is a long noncoding RNA that has been proposed to control retinal cell specification, stem cell differentiation and alternative splicing of schizophrenia-related genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25145264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628989", "endSection": "title" }, { "offsetInBeginSection": 560, "offsetInEndSection": 849, "text": "Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628989", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 971, "text": "Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23628989", "endSection": "title" } ] }, { "body": "Is butterfly rash a symptom of Systemic lupus erythematosus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8000104", "http://www.ncbi.nlm.nih.gov/pubmed/27878308", "http://www.ncbi.nlm.nih.gov/pubmed/24948869", "http://www.ncbi.nlm.nih.gov/pubmed/19082832", "http://www.ncbi.nlm.nih.gov/pubmed/7065728", "http://www.ncbi.nlm.nih.gov/pubmed/1440087", "http://www.ncbi.nlm.nih.gov/pubmed/7979581", "http://www.ncbi.nlm.nih.gov/pubmed/17728372", "http://www.ncbi.nlm.nih.gov/pubmed/1765991", "http://www.ncbi.nlm.nih.gov/pubmed/1437923", "http://www.ncbi.nlm.nih.gov/pubmed/23934402", "http://www.ncbi.nlm.nih.gov/pubmed/9598885", "http://www.ncbi.nlm.nih.gov/pubmed/3769804", "http://www.ncbi.nlm.nih.gov/pubmed/2674762", "http://www.ncbi.nlm.nih.gov/pubmed/23019977", "http://www.ncbi.nlm.nih.gov/pubmed/17113236", "http://www.ncbi.nlm.nih.gov/pubmed/17569152", "http://www.ncbi.nlm.nih.gov/pubmed/20120828", "http://www.ncbi.nlm.nih.gov/pubmed/2585838", "http://www.ncbi.nlm.nih.gov/pubmed/7607795", "http://www.ncbi.nlm.nih.gov/pubmed/7924059", "http://www.ncbi.nlm.nih.gov/pubmed/25516474", "http://www.ncbi.nlm.nih.gov/pubmed/12672213" ], "ideal_answer": [ "Yes, butterfly rash is symptom of Systemic lupus erythematosus." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8857", "http://www.disease-ontology.org/api/metadata/DOID:9074", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008180" ], "type": "yesno", "id": "58bfeb2b02b8c6095300001a", "snippets": [ { "offsetInBeginSection": 374, "offsetInEndSection": 605, "text": "Diagnosing SLE can be challenging because of the myriad of clinical features and substantial variability between patients. Cutaneous involvement is present in about 60% of cases and typically manifests as a malar or butterfly rash.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20120828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "The prevalence of systemic lupus erythematosus (SLE) is 28 per 100,000. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20120828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis (AIH) and systemic lupus erythematosus (SLE). The patient presented with jaundice, hepatosplenomegaly, malaise, polyarthralgia, arthritis and butterfly rash on the face.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17569152", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 764, "text": "Some of the clinical characteristics of SLE patients observed were nephritis (53.7%), fever (53.26%), neuropsychological disorder (36.18%), malar/butterfly rash (27.6%), pulmonary disorder (22.6%), photosensitivity (21.6%), cardiac involvement (21.1%) and oral ulcers (19.09%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17728372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Systemic lupus erythematosus and infections: a retrospective study in Saudis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17728372", "endSection": "title" }, { "offsetInBeginSection": 801, "offsetInEndSection": 1123, "text": "The prevalence of the following manifestations was significantly higher for pediatric than for adult-onset disease including: lupus nephritis (43% pediatric vs 26.4% for adult-onset), hematological disorders (57% vs 36.4%), photosensitivity (20% vs 9%), butterfly rash (61% vs 35.5%) and mucosal ulceration (11.4% vs 4%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with highest prevalence among women of childbearing age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516474", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 1069, "text": "We described a unique case of a 25-year-old Arab young woman who was diagnosed with SLE, depending on clinical, laboratory investigations and after she had fulfilled the diagnostic criteria for SLE and had presented the following findings: constitutional findings (fatigue, fever, and arthralgia); dermatologic finding (photosensitivity and butterfly rash); chronic renal failure (proteinuria up to 400 mg in 24 hours); hematologic and antinuclear antibodies (positivity for antinuclear factor (ANF), anti-double-stranded DNA antibodies, direct Coombs, ANA and anti-DNA, low C4 and C3, aCL by IgG and IgM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24948869", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 771, "text": "Grade 1 and 2-3 inflammatory process occurred in 53 (63%) and 31 (37%) patients respectively. Symptom complexes \"systemic inflammation\", \"butterfly rash\", \"wrist petechiae\", \"enanthema of the oral mucous membrane\", and other lesions were regarded as the markers of SLE activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23019977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Systemic lupus erythematosus (SLE) remains a challenging medical problem. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23019977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syndrome of rheumatoid arthritis and systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17113236", "endSection": "title" }, { "offsetInBeginSection": 125, "offsetInEndSection": 224, "text": "A butterfly rash on the patient's face suggested a diagnosis of systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19082832", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 222, "text": "A butterfly rash on the patients face suggested a diagnosis of systemic lupus erythematosus (SLE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19082832", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 437, "text": "The diagnosis of SLE could be excluded and the butterfly rash attributed to a laminar hemorrhage, an ecchymosis due to the autoimmune thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19082832", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 447, "text": "We describe a case of KD who developed a typical butterfly rash, reminiscent of SLE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12672213", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 262, "text": "The diagnosis of SLE was made 22 years ago based on Raynaud's phenomenon, butterfly rash, hair loss, photosensitivity and positive antinuclear antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1440087", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 770, "text": "Symptom complexes \"systemic inflammation\", \"butterfly rash\", \"wrist petechiae\", \"enanthema of the oral mucous membrane\", and other lesions were regarded as the markers of SLE activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23019977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syndrome of rheumatoid arthritis and systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17113236", "endSection": "title" }, { "offsetInBeginSection": 111, "offsetInEndSection": 391, "text": "To investigate, various unspecific, but otherwise typical clinical symptoms of skin and mucous membranes that arise in SLE patients other than those defined as SLE criteria such as butterfly rash, chronic cutaneous lupus erythematosus, oral ulcers, and increased photosensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27878308", "endSection": "abstract" } ] }, { "body": "What is the function of yeast Clr4 on chromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9620780", "http://www.ncbi.nlm.nih.gov/pubmed/11273706", "http://www.ncbi.nlm.nih.gov/pubmed/16127433", "http://www.ncbi.nlm.nih.gov/pubmed/17504808", "http://www.ncbi.nlm.nih.gov/pubmed/23771057", "http://www.ncbi.nlm.nih.gov/pubmed/21060862", "http://www.ncbi.nlm.nih.gov/pubmed/8937982", "http://www.ncbi.nlm.nih.gov/pubmed/19117951" ], "ideal_answer": [ "Clr4 is known to regulate silencing and switching at the mating-type loci and to affect chromatin structure at centromeres. The Clr4 methyltransferase determines the subnuclear localization of the mating-type region in fission yeast. Heterochromatin assembly in fission yeast depends on the Clr4 histone methyltransferase, which targets H3K9." ], "type": "summary", "id": "58ab1e19396a458e5000000f", "snippets": [ { "offsetInBeginSection": 308, "offsetInEndSection": 455, "text": "Mutations in the clr4+, rik1+ and swi6+ genes dramatically reduce silencing at certain centromeric regions and cause elevated chromosome loss rates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8937982", "endSection": "abstract" }, { "offsetInBeginSection": 918, "offsetInEndSection": 1076, "text": "The Swi6 protein was found to be delocalised from all three silent chromosomal regions, and dispersed within the nucleus, in both clr4 and rik1 mutant cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8937982", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1469, "text": "Mutations in clr4, rik1 and swi6 also result in elevated sensitivity to reagents which destabilise microtubules and show a synergistic interaction with a mutation in the beta-tubulin gene (nda3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8937982", "endSection": "abstract" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1770, "text": "These observations suggest that clr4+ and rik1+ must play a role in the assembly of Swi6p into a transcriptionally silent, inaccessible chromatin structure at fission yeast centromeres which is required to facilitate interactions with spindle microtubules and to ensure normal chromosome segregation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8937982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9620780", "endSection": "title" }, { "offsetInBeginSection": 752, "offsetInEndSection": 868, "text": "Like Su(var)3-9p, Clr4p contains SET and chromo domains, motifs found in proteins that modulate chromatin structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9620780", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1188, "text": "Surprisingly, RNA differential display experiments demonstrated that clr4+ can mediate transcriptional activation of certain other loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9620780", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1400, "text": "These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9620780", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 576, "text": "Clr4 is known to regulate silencing and switching at the mating-type loci and to affect chromatin structure at centromeres. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11273706", "endSection": "abstract" }, { "offsetInBeginSection": 638, "offsetInEndSection": 743, "text": "Mutations in Cul4 result in defective localization of Clr4 and loss of silencing at heterochromatic loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16127433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "The Clr4 methyltransferase determines the subnuclear localization of the mating-type region in fission yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17504808", "endSection": "title" }, { "offsetInBeginSection": 623, "offsetInEndSection": 789, "text": "In a strain lacking the histone methyltransferase Clr4, crucial for the formation of heterochromatin, the mating-type region had a random localization in the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17504808", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1238, "text": "Cut4 and Cut9 interact directly with Swi6/HP1 and Clr4, whereas the mutant Cut4 does not, suggesting that a direct physical interaction of APC subunits Cut4 and Cut9 with Swi6 and Clr4 is instrumental in heterochromatin assembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117951", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1858, "text": "Thus, APC and heterochromatin proteins Swi6 and Clr4 play a mutually cooperative role in heterochromatin assembly, thereby ensuring chromosomal integrity, inheritance, and segregation during mitosis and meiosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117951", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 426, "text": "Positive feedback mechanisms that link the RNAi pathway and the Clr4/Suv39h1 histone H3K9 methyltransferase complex (Clr-C) result in requirements for H3K9 methylation for full siRNA production and for siRNA production to achieve full histone methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21060862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Heterochromatin assembly in fission yeast depends on the Clr4 histone methyltransferase, which targets H3K9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23771057", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1277, "text": "These analyses place Sir2 and H3K14 deacetylation upstream of Clr4 recruitment during heterochromatin assembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23771057", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1399, "text": "These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9620780", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1401, "text": "These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9620780", "endSection": "abstract" } ] }, { "body": "What is the role of LIMT lncRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "http://www.ncbi.nlm.nih.gov/pubmed/27123924" ], "ideal_answer": [ "LINC01089 (LncRNA Inhibiting Metastasis; LIMT) is a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo.", "LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069584", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064726", "http://www.uniprot.org/uniprot/BCAS1_MOUSE", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000072656", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058922", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085", "http://www.uniprot.org/uniprot/BRMS1_HUMAN", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018567", "http://www.uniprot.org/uniprot/BCAS1_HUMAN" ], "type": "summary", "id": "5896381a78275d0c4a00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "title" }, { "offsetInBeginSection": 602, "offsetInEndSection": 1301, "text": "This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in\u00a0vitro and tumor metastasis in\u00a0vivo In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 912, "text": "Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1031, "text": "Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1295, "text": "We also find that LIMT inhibits extracellular matrix invasion of mammary cells in\u00a0vitro and tumor metastasis in\u00a0vivo In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 916, "text": "Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "title" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1301, "text": "We also find that LIMT inhibits extracellular matrix invasion of mammary cells in\u00a0vitro and tumor metastasis in\u00a0vivo In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485121", "endSection": "abstract" } ] }, { "body": "Is infertility characteristic of individuals with Fanconi anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24438373", "http://www.ncbi.nlm.nih.gov/pubmed/16946016", "http://www.ncbi.nlm.nih.gov/pubmed/12913077", "http://www.ncbi.nlm.nih.gov/pubmed/20598602", "http://www.ncbi.nlm.nih.gov/pubmed/19101574", "http://www.ncbi.nlm.nih.gov/pubmed/25016020", "http://www.ncbi.nlm.nih.gov/pubmed/20494929", "http://www.ncbi.nlm.nih.gov/pubmed/16078221", "http://www.ncbi.nlm.nih.gov/pubmed/21951543", "http://www.ncbi.nlm.nih.gov/pubmed/10915769", "http://www.ncbi.nlm.nih.gov/pubmed/25575015", "http://www.ncbi.nlm.nih.gov/pubmed/15128600", "http://www.ncbi.nlm.nih.gov/pubmed/21915857" ], "ideal_answer": [ "Yes, infertility is characteristic of individuals with Fanconi anemia." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:2355", "http://www.disease-ontology.org/api/metadata/DOID:13636", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007248", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007247", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007246", "http://www.disease-ontology.org/api/metadata/DOID:5223" ], "type": "yesno", "id": "58b6d26122d300530900000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25016020", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 888, "text": "Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25016020", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 217, "text": "In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24438373", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1740, "text": "Substantially reduced AMH levels in females with FA suggest a primary ovarian defect associated with reduced fertility. Measurement of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at regular intervals may be useful for the timely management of complications related to POI such as subfertility/infertility, osteoporosis, and menopausal symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24438373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21951543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Reduced fertility is one clinical manifestation among other well known Fanconi anemia features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20494929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21951543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12913077", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21951543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 452, "text": "To potentially reduce late effects of malignancy, chronic graft-versus-host disease (GVHD), endocrinopathy, and infertility in patients with Fanconi anemia (FA) undergoing HLA-matched related donor hematopoietic cell transplantation (HCT), we developed a regimen using fludarabine (FLU), cyclophosphamide (CY), and anti-thymocyte globulin (ATG) followed by infusion of T-cell depleted (TCD) bone marrow (BM) or unmanipulated umbilical cord blood (UCB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16078221", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 998, "text": "Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15128600", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 697, "text": "FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a rare genetically heterogeneous autosomal recessive disorder characterized by bone marrow failure, endocrine tissue cancer susceptibility, and infertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16946016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24438373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Fanconi anemia (FA) is a complex cancer susceptibility disorder associated with DNA repair defects and infertility, yet the precise function of the FA proteins in genome maintenance remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20598602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Fanconi anemia (FA) is a genetic disease resulting in bone marrow failure, high cancer risks, and infertility, and developmental anomalies including microphthalmia, microcephaly, hypoplastic radius and thumb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19101574", "endSection": "abstract" } ] }, { "body": "What are Kupffer cells and what is their role?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15693545", "http://www.ncbi.nlm.nih.gov/pubmed/26908374", "http://www.ncbi.nlm.nih.gov/pubmed/8621159", "http://www.ncbi.nlm.nih.gov/pubmed/26553134", "http://www.ncbi.nlm.nih.gov/pubmed/27717685", "http://www.ncbi.nlm.nih.gov/pubmed/12964033", "http://www.ncbi.nlm.nih.gov/pubmed/26613891", "http://www.ncbi.nlm.nih.gov/pubmed/1748476" ], "ideal_answer": [ "Kupffer cells (KCs)are hepatic macrophages which can secrete matrix metalloproteinases (MMPs), and can contribute to decreased hepatic insulin sensitivity. KCs may play a role in the development of drug induced liver injury (DILI)", "Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI). Hepatic macrophages consist of Kupffer cells, which are originated from the fetal yolk-sack, and infiltrated bone marrow-derived monocytes/macrophages. " ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007728" ], "type": "summary", "id": "58cdb38f02b8c60953000041", "snippets": [ { "offsetInBeginSection": 45, "offsetInEndSection": 132, "text": "Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27717685", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 311, "text": "Hepatic macrophages consist of Kupffer cells, which are originated from the fetal yolk-sack, and infiltrated bone marrow-derived monocytes/macrophages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26908374", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 967, "text": "Kupffer cells (KCs) are the main source of MMP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26613891", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 949, "text": "liver, both Kupffer cells and recruited hepatic macrophages can contribute to decreased hepatic insulin sensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26553134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Macrophages such as Kupffer cells in the liver are multifunctional cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8621159", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 478, "text": "Kupffer cells--the resident macrophages of the liver--are able to release a tremendous array of mediators upon inflammatory conditions, such as infection, and their role in innate immunity is well described in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15693545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Kupffer cells are the tissue macrophages in the liver and play an important role in the defense mechanisms of the body", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12964033", "endSection": "abstract" } ] }, { "body": "What is known about saponins in crops and human consumption?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8121473", "http://www.ncbi.nlm.nih.gov/pubmed/23533206", "http://www.ncbi.nlm.nih.gov/pubmed/9839832", "http://www.ncbi.nlm.nih.gov/pubmed/11336236", "http://www.ncbi.nlm.nih.gov/pubmed/20725585" ], "ideal_answer": [ "Saponins are considered antinutrients for humans and have a bitter taste. They should be removed from the crops before consumption." ], "type": "summary", "id": "58cd729502b8c6095300003d", "snippets": [ { "offsetInBeginSection": 335, "offsetInEndSection": 706, "text": "Saponins are readily soluble in water and are approved by the US FDA for inclusion in beverages intended for human consumption. The addition of saponins to existing water supplies offers a new form of intervention into the cycle of rotavirus infection. We believe that saponins will 'coat' the epithelium of the host's small intestine and prevent attachment of rotavirus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20725585", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 762, "text": "The levels of antinutrients in meal from the raw seeds were: trypsin inhibitor activity (14.6-28.7 mg trypsin inhibited/g), lectin (25.6-52.2 unit; one unit is the reverse of minimum amount of mg meal/ml assay which produced haemagglutination), saponins (1.9-2.3% as diosgenin equivalent) and phytate (8.4-10%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9839832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Quinoa cultivars currently grown in North America and Europe require removal of bitter-tasting saponins from the grain prior to human consumption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336236", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 685, "text": " Antinutrients, including phytate, glycoside, saponin and tannin, were screened and quantified. Phytate (112.82 \u00b1 0.1 mg/100 g), glycoside (2.33 \u00b1 0.00 mg/100 g), saponin (1.31 \u00b1 0.00 mg/100g) and tannin (0.21 \u00b1 0.00 mg/100 g) were present in the fruit but phlobatanin and glycosides with steroidal rings were not found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533206", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 279, "text": "antinutritional factors (phytic acid, trypsin inhibitor activity (TIA) and saponins)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8121473", "endSection": "abstract" } ] }, { "body": "Is golimumab effective for ulcerative colitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24955447", "http://www.ncbi.nlm.nih.gov/pubmed/27494322", "http://www.ncbi.nlm.nih.gov/pubmed/24502344", "http://www.ncbi.nlm.nih.gov/pubmed/26907481", "http://www.ncbi.nlm.nih.gov/pubmed/25609972", "http://www.ncbi.nlm.nih.gov/pubmed/24285003", "http://www.ncbi.nlm.nih.gov/pubmed/26738756", "http://www.ncbi.nlm.nih.gov/pubmed/24774504", "http://www.ncbi.nlm.nih.gov/pubmed/18683105", "http://www.ncbi.nlm.nih.gov/pubmed/27498886", "http://www.ncbi.nlm.nih.gov/pubmed/25876561", "http://www.ncbi.nlm.nih.gov/pubmed/23344099", "http://www.ncbi.nlm.nih.gov/pubmed/23735746", "http://www.ncbi.nlm.nih.gov/pubmed/26600980", "http://www.ncbi.nlm.nih.gov/pubmed/24842416", "http://www.ncbi.nlm.nih.gov/pubmed/24506179", "http://www.ncbi.nlm.nih.gov/pubmed/26786341", "http://www.ncbi.nlm.nih.gov/pubmed/27440869", "http://www.ncbi.nlm.nih.gov/pubmed/25294262", "http://www.ncbi.nlm.nih.gov/pubmed/25729432", "http://www.ncbi.nlm.nih.gov/pubmed/23897288", "http://www.ncbi.nlm.nih.gov/pubmed/25817087", "http://www.ncbi.nlm.nih.gov/pubmed/27699641", "http://www.ncbi.nlm.nih.gov/pubmed/23770005", "http://www.ncbi.nlm.nih.gov/pubmed/24160948", "http://www.ncbi.nlm.nih.gov/pubmed/26893582", "http://www.ncbi.nlm.nih.gov/pubmed/27695502", "http://www.ncbi.nlm.nih.gov/pubmed/27723166" ], "ideal_answer": [ "Yes. Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003093", "http://www.disease-ontology.org/api/metadata/DOID:8577", "http://www.biosemantics.org/jochem#4002191" ], "type": "yesno", "id": "5896e4d478275d0c4a000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Initial experience with golimumab in clinical practice for ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26786341", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "BACKGROUND: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26786341", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1341, "text": "CONCLUSIONS: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26786341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Cost-Effectiveness Analysis of 1-Year Treatment with Golimumab/Standard Care and Standard Care Alone for Ulcerative Colitis in Poland.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27494322", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "OBJECTIVE: The objective of this study was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of ulcerative colitis with golimumab/standard care and standard care alone in Poland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27494322", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1575, "text": "CONCLUSIONS: The biologic treatment of ulcerative colitis patients with golimumab/standard care is more effective but also more costly compared with standard care alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27494322", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 448, "text": "Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long-term remission of IBD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723166", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 457, "text": "Furthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27699641", "endSection": "abstract" }, { "offsetInBeginSection": 1488, "offsetInEndSection": 1750, "text": "CONCLUSIONS: No significant differences in efficacy in the maintenance phase between infliximab and golimumab or adalimumab were revealed. Infliximab proved to be more effective than adalimumab but of similar efficacy to that of golimumab in the induction phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27695502", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 811, "text": "In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-\u03b1) inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25609972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Golimumab, a human anti-TNF antibody, is effective in patients with ulcerative colitis, according to new findings from an international phase III double-blind trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23897288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Golimumab for moderately to severely active ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498886", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23770005", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23735746", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 484, "text": "Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-\u03b1 (TNF\u03b1), was evaluated as maintenance therapy in TNF\u03b1 antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy.We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23770005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Golimumab, a human anti-TNF antibody, is effective in patients with ulcerative colitis, according to new findings from an international phase III double-blind trial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23897288", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 646, "text": "The purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents.Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285003", "endSection": "abstract" }, { "offsetInBeginSection": 1593, "offsetInEndSection": 1794, "text": "Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24955447", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1471, "text": "The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively.This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24506179", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 769, "text": "The biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25729432", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 327, "text": "We evaluated subcutaneous golimumab induction therapy in TNF-\u03b1 antagonist-na\u00efve patients with moderate-to-severe UC despite conventional treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23735746", "endSection": "abstract" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1843, "text": "Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24955447", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 647, "text": "The purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents.Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285003", "endSection": "abstract" }, { "offsetInBeginSection": 1593, "offsetInEndSection": 1795, "text": "Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24955447", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 771, "text": "The biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25729432", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1533, "text": "The incremental cost-utility ratio of golimumab/standard care compared to the standard care alone is estimated to be 391,252 PLN/QALY gained (93,155 \u20ac/QALYG) from public payer perspective and 374,377 PLN/QALY gained (89,137 \u20ac/QALYG) from social perspective.The biologic treatment of ulcerative colitis patients with golimumab/standard care is more effective but also more costly compared with standard care alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27494322", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1472, "text": "The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively.This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24506179", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 819, "text": "Recently, 2 new antibodies have been approved: golimumab is a new option for ulcerative colitis and with another more selective mechanism of action; vedolizumab could be useful for ulcerative colitis as well as Crohn's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294262", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 588, "text": "The present review summarizes the literature on the role of golimumab, a new anti TNF agent, in ulcerative colitis.Literature search was done on PubMed using the search terms 'golimumab' AND 'ulcerative colitis' from inception till March 2016.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "The aim of this systematic review was to evaluate the efficacy and safety of biological agents (vedolizumab, abatacept, visilizumab, golimumab) in patients with active moderate to severe ulcerative colitis.This paper was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24955447", "endSection": "abstract" }, { "offsetInBeginSection": 1632, "offsetInEndSection": 1834, "text": "Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24955447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 513, "text": "BACKGROUND & AIMS: Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-\u00e1 (TNF\u00e1), was evaluated as maintenance therapy in TNF\u00e1 antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy.METHODS: We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23770005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND & AIMS: Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -\u00e1, for treatment of ulcerative colitis (UC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23735746", "endSection": "abstract" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1476, "text": "This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24506179", "endSection": "abstract" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1793, "text": "Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24955447", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 648, "text": "Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Golimumab for moderately to severely active ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498886", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Initial experience with golimumab in clinical practice for ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26786341", "endSection": "title" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1045, "text": "Golimumab was found to be effective and safe in inducing and maintaining clinical remission, clinical response and mucosal healing in patients with UC in the two registration trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "[Golimumab Therapy in Ulcerative Colitis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26907481", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Golimumab: clinical update on its use for ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25876561", "endSection": "title" }, { "offsetInBeginSection": 558, "offsetInEndSection": 624, "text": "This review will focus on golimumab therapy in ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26907481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "To assess golimumab pharmacokinetics [PK] and exposure-response [ER] in adults with moderate-to-severe ulcerative colitis [UC] from the Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment [PURSUIT] studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440869", "endSection": "abstract" } ] }, { "body": "What is the role of histone variant H2A.W?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "http://www.ncbi.nlm.nih.gov/pubmed/25983206", "http://www.ncbi.nlm.nih.gov/pubmed/25781491" ], "ideal_answer": [ "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis. The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants. ", "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants Covalent histone modifications (e.g.", "The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. Histone chaperones escort histones, and play key functions during nucleosome assembly/disassembly and in nucleosome structure configuration. Here we focus on plant histone H2A/H2B chaperones, particularly members of the NUCLEOSOME ASSEMBLY PROTEIN-1 (NAP1) and FACILITATES CHROMATIN TRANSCRIPTION (FACT) families, discussing their molecular features, properties, regulation and function. We further discuss roles of NAP1 and FACT in chromatin-based processes, such as transcription, DNA replication and repair. Future major challenges remain in order to define in more detail the overlapping and specific roles of various members of the NAP1 family as well as differences and similarities between NAP1 and FACT family members, and to identify and characterize their partners as well as new families of chaperones to understand histone variant incorporation and chromatin target specificity.", " In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization.", "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis", "Histone variants play crucial roles in gene expression, genome integrity, and chromosome segregation. The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. Histone chaperones escort histones, and play key functions during nucleosome assembly/disassembly and in nucleosome structure configuration. Covalent histone modifications (e.g. ubiquitination, phosphorylation, methylation, acetylation) and H2A variants (H2A.Z, H2A.X and H2A.W) are also discussed in view of their crucial importance in modulating nucleosome organization and function.", "The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization." ], "type": "summary", "id": "58ab1f209ef3c34033000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "title" }, { "offsetInBeginSection": 235, "offsetInEndSection": 403, "text": "The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 669, "text": "In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 795, "text": " In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25983206", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 913, "text": "Covalent histone modifications (e.g. ubiquitination, phosphorylation, methylation, acetylation) and H2A variants (H2A.Z, H2A.X and H2A.W) are also discussed in view of their crucial importance in modulating nucleosome organization and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25781491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "title" }, { "offsetInBeginSection": 530, "offsetInEndSection": 670, "text": "In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 669, "text": "In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "title" }, { "offsetInBeginSection": 670, "offsetInEndSection": 844, "text": "Similarities in conserved motifs between H2A.W and another H2A variant in metazoans suggest that plants and animals share common mechanisms for heterochromatin condensation..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 529, "text": "In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24995981", "endSection": "abstract" } ] }, { "body": "Which are the main brain dysfunctions caused by hyperbilirubinemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3174510", "http://www.ncbi.nlm.nih.gov/pubmed/8631524", "http://www.ncbi.nlm.nih.gov/pubmed/27746217", "http://www.ncbi.nlm.nih.gov/pubmed/25524299", "http://www.ncbi.nlm.nih.gov/pubmed/21575408", "http://www.ncbi.nlm.nih.gov/pubmed/22966025", "http://www.ncbi.nlm.nih.gov/pubmed/23283699", "http://www.ncbi.nlm.nih.gov/pubmed/19754366", "http://www.ncbi.nlm.nih.gov/pubmed/11726727", "http://www.ncbi.nlm.nih.gov/pubmed/23086523", "http://www.ncbi.nlm.nih.gov/pubmed/25793115", "http://www.ncbi.nlm.nih.gov/pubmed/14684236", "http://www.ncbi.nlm.nih.gov/pubmed/25534357", "http://www.ncbi.nlm.nih.gov/pubmed/24309481", "http://www.ncbi.nlm.nih.gov/pubmed/27393040", "http://www.ncbi.nlm.nih.gov/pubmed/21163242", "http://www.ncbi.nlm.nih.gov/pubmed/17342778", "http://www.ncbi.nlm.nih.gov/pubmed/16361175", "http://www.ncbi.nlm.nih.gov/pubmed/23375301", "http://www.ncbi.nlm.nih.gov/pubmed/8340096", "http://www.ncbi.nlm.nih.gov/pubmed/20971088", "http://www.ncbi.nlm.nih.gov/pubmed/26480925", "http://www.ncbi.nlm.nih.gov/pubmed/18821100" ], "ideal_answer": [ "Bilirubin-induced neurologic dysfunction (BIND) and classical kernicterus are the main dysfunctions of hyperbilirubinemia, whenever bilirubin levels exceed the capacity of the brain defensive mechanisms in preventing its entrance and cytotoxicity. Bilirubin accumulation may lead to deficits in auditory, cognitive, and motor processing, due to neuronal cell death, reduced myelination and glial activation." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006933", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006932", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051556", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001921", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001663" ], "type": "summary", "id": "58c66a4b02b8c60953000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 616, "text": "Bilirubin-induced neurologic dysfunction (BIND) and classical kernicterus are clinical manifestations of moderate to severe hyperbilirubinemia whenever bilirubin levels exceed the capacity of the brain defensive mechanisms in preventing its entrance and cytotoxicity. In such circumstances and depending on the associated co-morbidities, bilirubin accumulation may lead to short- or long-term neurodevelopmental disabilities, which may include deficits in auditory, cognitive, and motor processing. Neuronal cell death, astrocytic reactivity, and microglia activation are part of the bilirubin-induced pathogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Reduced Myelination and Increased Glia Reactivity Resulting from Severe Neonatal Hyperbilirubinemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26480925", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Bilirubin-induced neurologic dysfunction (BIND) and kernicterus has been used to describe moderate to severe neurologic dysfunction observed in children exposed to excessive levels of total serum bilirubin (TSB) during the neonatal period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26480925", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 769, "text": "Histologic studies of brain tissue demonstrate that the onset of severe neonatal hyperbilirubinemia, characterized by seizures, leads to alterations in myelination and glia reactivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26480925", "endSection": "abstract" }, { "offsetInBeginSection": 1467, "offsetInEndSection": 1702, "text": "Thus, kernicterus in this model displays not only axonal damage but also myelination deficits and glial activation in different brain regions that are usually related to the neurologic sequelae observed after severe hyperbilirubinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26480925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "Advances in the care of neonatal hyperbilirubinemia have led to a decreased incidence of kernicterus. However, neonatal exposure to high levels of bilirubin continues to cause severe motor symptoms and cerebral palsy (CP). Exposure to moderate levels of unconjugated bilirubin may also cause damage to the developing central nervous system, specifically the basal ganglia and cerebellum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25524299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "High levels of serum unconjugated bilirubin (UCB) in newborns are associated with axonal damage and glial reactivity that may contribute to subsequent neurologic injury and encephalopathy (kernicterus). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Hyperbilirubinemia remains one of the most frequent clinical diagnoses in the neonatal period. This condition may lead to the deposition of unconjugated bilirubin (UCB) in the central nervous system, causing nerve cell damage by molecular and cellular mechanisms that are still being clarified. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23283699", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 254, "text": "\"Kernicterus\" is a term currently used to describe bilirrubin induced brain injury in the neuro-pathological studies. This is a confusing term and nowadays we prefer bilirrubin encephalopathy or bilirrubin induced neurological dysfunction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21163242", "endSection": "abstract" }, { "offsetInBeginSection": 1203, "offsetInEndSection": 1390, "text": "We then review the possible alteration of the neuroprotective and trophic barrier functions in the course of bilirubin-induced neurological dysfunctions resulting from hyperbilirubinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19754366", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 349, "text": "It has been suggested recently that there is an association between hyperbilirubinemia and long-term neurologic dysfunctions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17342778", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 875, "text": "In this article, we review computational insights into the brain dysfunctions underlying Parkinson's disease, Huntington's disease, and dystonia, with particular foci on dysfunctions of the dopamine system, basal ganglia pathways, and neuronal oscillations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27393040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18821100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Neonatal jaundice is a common cause of sensorneural hearing loss in children.We aimed to detect the neurotoxic effects of pathologic hyperbilirubinemia on brain stem and auditory tract by auditory brain stem evoked response (ABR) which could predict early effects of hyperbilirubinemia.This case-control study was performed on newborns with pathologic hyperbilirubinemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793115", "endSection": "abstract" }, { "offsetInBeginSection": 1763, "offsetInEndSection": 2138, "text": "For example, the mean latencies time of wave I was significantly higher in right ear of the case group than in controls (2.16 \u00b1 0.26 vs. 1.77 \u00b1 0.15 milliseconds, respectively) (P < 0.001).Pathologic hyperbilirubinemia causes acute disorder on brain stem function; therefore, early diagnosis of neonatal jaundice for prevention of bilirubin neurotoxic effects is essential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793115", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1553, "text": "Wave amplitudes are valuable BAER variables to detect functional impairment of the brainstem and auditory pathway in neonatal hyperbilirubinemia, and are recommended to be used in assessing bilirubin neurotoxicity to the neonatal brain.Copyright \u00a9 2013 European Paediatric Neurology Society", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24309481", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 767, "text": "Histologic studies of brain tissue demonstrate that the onset of severe neonatal hyperbilirubinemia, characterized by seizures, leads to alterations in myelination and glia reactivity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26480925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "[Characteristics of auditory brain stem response in neonatal hyperbilirubinemia induced by different causes].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21575408", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Excessive hyperbilirubinemia in human neonates can cause permanent dysfunction of the auditory system, as assessed with brainstem auditory evoked potentials (BAEPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20971088", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 571, "text": "A recent surge in reported cases of classical kernicterus, due in part to earlier hospital discharge and relaxation of treatment criteria for hyperbilirubinemia, and new reports of hyperbilirubinemia-induced auditory dysfunction using evoked potential based infant testing and hearing screening, underscore the need to better understand how hyperbilirubinemia causes brain damage in some infants, especially because the damage is preventable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14684236", "endSection": "abstract" }, { "offsetInBeginSection": 1944, "offsetInEndSection": 2128, "text": "Pathologic hyperbilirubinemia causes acute disorder on brain stem function; therefore, early diagnosis of neonatal jaundice for prevention of bilirubin neurotoxic effects is essential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793115", "endSection": "abstract" } ] }, { "body": "Does mTOR regulate the translation of MAPKAPK2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26269117", "http://www.ncbi.nlm.nih.gov/pubmed/26280535" ], "ideal_answer": [ "Yes. mTOR regulates the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous senescence-associated secretory phenotype (SASP) components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/MAPK2_RABIT", "http://amigo.geneontology.org/amigo/term/GO:0070438", "http://www.uniprot.org/uniprot/MAPK2_CRILO", "http://amigo.geneontology.org/amigo/term/GO:0038201", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058570", "http://www.uniprot.org/uniprot/MAPK2_HUMAN", "http://www.uniprot.org/uniprot/MAPK2_DROME" ], "type": "yesno", "id": "58967c9978275d0c4a000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280535", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1073, "text": "Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280535", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 569, "text": "Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280535", "endSection": "title" }, { "offsetInBeginSection": 411, "offsetInEndSection": 571, "text": "Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280535", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 572, "text": "Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280535", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1475, "text": "Both Beclin1-PI3KIII and Beclin1-MAPKAPK2 interactions as were remarkably affected by silencing either ATM or MAPK14.ATM promoted IR-induced autophagy via the MAPK14 pathway, mTOR pathway and Beclin1/PI3KIII complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26269117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280535", "endSection": "title" } ] }, { "body": "What chromosome is affected in Turner's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19909521", "http://www.ncbi.nlm.nih.gov/pubmed/20197675", "http://www.ncbi.nlm.nih.gov/pubmed/697225", "http://www.ncbi.nlm.nih.gov/pubmed/15797949", "http://www.ncbi.nlm.nih.gov/pubmed/25800473", "http://www.ncbi.nlm.nih.gov/pubmed/20017317", "http://www.ncbi.nlm.nih.gov/pubmed/8517687", "http://www.ncbi.nlm.nih.gov/pubmed/26757887", "http://www.ncbi.nlm.nih.gov/pubmed/16821224", "http://www.ncbi.nlm.nih.gov/pubmed/17663292", "http://www.ncbi.nlm.nih.gov/pubmed/8151646", "http://www.ncbi.nlm.nih.gov/pubmed/10689047", "http://www.ncbi.nlm.nih.gov/pubmed/3625764", "http://www.ncbi.nlm.nih.gov/pubmed/23602925", "http://www.ncbi.nlm.nih.gov/pubmed/1240972", "http://www.ncbi.nlm.nih.gov/pubmed/11807897", "http://www.ncbi.nlm.nih.gov/pubmed/22711287", "http://www.ncbi.nlm.nih.gov/pubmed/12667526", "http://www.ncbi.nlm.nih.gov/pubmed/26322078", "http://www.ncbi.nlm.nih.gov/pubmed/20122165" ], "ideal_answer": [ "turner's syndrome (ts) is a chromosomal defect with partial or total absence of the x chromosome.", "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome.", "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome. ", "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome" ], "exact_answer": [ "X" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025063", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014960", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025064", "http://www.disease-ontology.org/api/metadata/DOID:3491", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014424", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D041321" ], "type": "factoid", "id": "58bca2f302b8c6095300000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26757887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Turner syndrome is a genetic disorder caused by the complete or partial absence of an X chromosome in affected women", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22711287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25800473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "CONTEXT: Turner syndrome (TS) is the most common genetic problem affecting women and occurs when an X chromosome is completely deleted, portions of an X chromosome are deleted, or chromosomal mosaicism occurs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15797949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Turner's syndrome (TS) is a chromosomal disorder that results from the loss of the entire or a part of the X-chromosome and occurs in 1/2,500 female births.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17663292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Women with Turner's syndrome (TS), who lack a complete X-chromosome, show an impairment in remembering faces and in classifying \"fear\" in face images.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12667526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The proposition that finger print variability between individuals might be reduced by the absence of an X-chromosome in Turner's syndrome was rejected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3625764", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 435, "text": "While the classic karyotype related to Turner's syndrome is 45,X, the majority of those affected actually have a mosaic chromosomal complement, most often with a second normal cell line (46,XX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20197675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "45,X Turner's syndrome in monozygotic twin sisters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1240972", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8517687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Turner syndrome is a chromosomal abnormality in which there is complete or partial absence of the X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26322078", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 160, "text": " To identify the origin and study the morphology of small supernumerary marker chromosome (sSMC) in Turner syndrome with 45, X/46, X, + mar karyotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20017317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Turner syndrome is a chromosomal disorder in which all or part of one X chromosome is missing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11807897", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 186, "text": "urner phenotype in this family is the result of deletion of the entire short arm of one X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/697225", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 122, "text": "X monosomic mice (39,XO) have a remarkably mild phenotype when compared to women with Turner syndrome (45,XO).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20122165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "X-monosomy is a form of Turner syndrome (TS) in which an entire X chromosome is missing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10689047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Turner's syndrome is defined as a congenital disease determining by quantitative and/or structural aberrations of one from two X chromosomes with frequent presence of mosaicism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16821224", "endSection": "abstract" } ] }, { "body": "What is the aim of the TRAP assay?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26965413", "http://www.ncbi.nlm.nih.gov/pubmed/24528514", "http://www.ncbi.nlm.nih.gov/pubmed/23288413", "http://www.ncbi.nlm.nih.gov/pubmed/26683936", "http://www.ncbi.nlm.nih.gov/pubmed/25225832", "http://www.ncbi.nlm.nih.gov/pubmed/23296661", "http://www.ncbi.nlm.nih.gov/pubmed/23913300" ], "ideal_answer": [ "Telomerase enzyme activity can be detected in whole cell lysates by a polymerase chain reaction (PCR)-based method referred to as the telomeric repeat amplification protocol (TRAP)." ], "exact_answer": [ "Telomerase enzyme activity can be detected in whole cell lysates by a polymerase chain reaction (PCR)-based method referred to as the telomeric repeat amplification protocol (TRAP)." ], "type": "factoid", "id": "58cd7af402b8c6095300003e", "snippets": [ { "offsetInBeginSection": 285, "offsetInEndSection": 452, "text": "Positive activity by the telomerase repeat amplification protocol (TRAP) was identified in cell extracts of Escherichia coli expressing a sequence-optimized hTERT gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26965413", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1031, "text": "The regulatory role of PCDH10 in telomerase activity was confirmed by a telomeric repeat amplification protocol (TRAP) assay, and the biological functions of it were characterized by in vitro proliferation, migration, and invasion assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26683936", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 947, "text": "TRAP assay is a standard method for detecting telomerase activity in various tissues or cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25225832", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 679, "text": "Telomerase activity was determined by TRAP assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24528514", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 858, "text": "The telomerase activity was evaluated by TRAP assay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288413", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 1178, "text": "The telomeric repeat amplification protocol (TRAP) represents an easy and rapid method for detection of telomerase activity in cells. A non-telomeric TS primer is extended by telomerase in the first step followed by the PCR amplification of the products. The PCR step renders this protocol very sensitive to detect telomerase activity at the single cell level making it compatible with the analysis of tumor samples. When run on a polyacrylamide gel, the PCR product is a characteristic ladder of bands due to the repetitive nature of telomeric DNA sequence. The densitometric analysis of the ladder allows the TRAP assay to be used for comparative quantification of telomerase activity in different samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23913300", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 371, "text": "Telomerase enzyme activity can be detected in whole cell lysates by a polymerase chain reaction (PCR)-based method referred to as the telomeric repeat amplification protocol (TRAP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23296661", "endSection": "abstract" } ] }, { "body": "Describe clinical applications of the PIM2 scoring system.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21132231", "http://www.ncbi.nlm.nih.gov/pubmed/25396011", "http://www.ncbi.nlm.nih.gov/pubmed/24051223", "http://www.ncbi.nlm.nih.gov/pubmed/25025075", "http://www.ncbi.nlm.nih.gov/pubmed/23940977", "http://www.ncbi.nlm.nih.gov/pubmed/23100008", "http://www.ncbi.nlm.nih.gov/pubmed/17549454", "http://www.ncbi.nlm.nih.gov/pubmed/24339640", "http://www.ncbi.nlm.nih.gov/pubmed/26337557", "http://www.ncbi.nlm.nih.gov/pubmed/20019069", "http://www.ncbi.nlm.nih.gov/pubmed/24862750", "http://www.ncbi.nlm.nih.gov/pubmed/26744626", "http://www.ncbi.nlm.nih.gov/pubmed/23429969", "http://www.ncbi.nlm.nih.gov/pubmed/24868211", "http://www.ncbi.nlm.nih.gov/pubmed/17251883", "http://www.ncbi.nlm.nih.gov/pubmed/25996320" ], "ideal_answer": [ "The Pediatric Index of Mortality 2 (PIM2) is one of the most commonly used scoring systems to predict mortality in patients admitted to pediatric intensive care units. The PIM2 score adequately discriminates survivors from non-survivor" ], "type": "summary", "id": "589a245678275d0c4a000023", "snippets": [ { "offsetInBeginSection": 433, "offsetInEndSection": 731, "text": "In this study, we examine if transfusion is an independent predictor of mortality, or if outcomes are merely a result of the initial severity as predicted by Pediatric Risk of Mortality (PRISM) III, Pediatric Index of Mortality (PIM2), and day 1 Pediatric Logistic Organ Dysfunction (PELOD) scores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26744626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "INTRODUCTION: The Pediatric Index of Mortality 2 (PIM2) is one of the most commonly used scoring systems to predict mortality in patients admitted to pediatric intensive care units (PICU) in Argentina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25996320", "endSection": "abstract" }, { "offsetInBeginSection": 1451, "offsetInEndSection": 1533, "text": "CONCLUSIONS: The PIM2 score adequately discriminates survivors from non-survivors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25996320", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1373, "text": "PIM2 scoring did not explain the outcome adequately, suggesting need for recalibration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24868211", "endSection": "abstract" }, { "offsetInBeginSection": 1214, "offsetInEndSection": 1436, "text": "CONCLUSION: PIM2 scoring system show adequate discriminatory function and well calibrated for the case mix of patients in PICU of Fayoum, Egypt. It can be used as beneficial tool for evaluation of risk adjusted mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25396011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The aim of the study was to explore the association between Glasgow Coma Scale (GCS), Paediatric Index of Mortality (PIM2) and Injury Severity Score (ISS), and the long-term outcome of children with injuries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Pediatric index of mortality 2 score as an outcome predictor in pediatric Intensive Care Unit in India.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339640", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND AND AIMS: Pediatric index of mortality (PIM) 2 score is one of the severity scoring systems being used for predicting outcome of patients admitted to intensive care units (ICUs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339640", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1434, "text": "CONCLUSION: PIM2 score discriminated well between survivors and death at PICU.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "OBJECTIVE: A study to validate and calibrate Pediatric Index of Mortality-2 (PIM2) in children admitted to our pediatric intensive care unit (PICU).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429969", "endSection": "abstract" }, { "offsetInBeginSection": 1205, "offsetInEndSection": 1304, "text": "CONCLUSION: PIM2 is a good index for prediction of mortality in our pediatric intensive care unit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The Pediatric Index of Mortality 2 (PIM2) is one of the most commonly used scoring systems to predict mortality in patients admitted to pediatric intensive care units (PICU) in Argentina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25996320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Pediatric Index of Mortality 2 (PIM2) and Pediatric Risk of Mortality (PRISM) are scoring systems to predict mortality likehood; thus, it is necessary to validate such predictors in Pediatric Intensive Care Units' population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21132231", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1397, "text": "Although PRISM, PIM and PIM2 have displayed good discrimination and calibration in the present setting, PIM is considered as the most accurate and appropriate tool for predicting mortality in the studied NICU.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019069", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1480, "text": "The PIM2 score adequately discriminates survivors from non-survivors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25996320", "endSection": "abstract" } ] }, { "body": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21738686", "http://www.ncbi.nlm.nih.gov/pubmed/22449192", "http://www.ncbi.nlm.nih.gov/pubmed/23595991", "http://www.ncbi.nlm.nih.gov/pubmed/23077180", "http://www.ncbi.nlm.nih.gov/pubmed/23463008", "http://www.ncbi.nlm.nih.gov/pubmed/21552206" ], "ideal_answer": [ "MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells. In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to na\u00efve pluripotency.", "1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development.", "Histone variant macroH2A confers resistance to nuclear reprogramming Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency.", "Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. The histone variant macroH2A acts as a component of an epigenetic multilayer that heritably maintains the silent X chromosome and has been shown to restrict tumor development.", "Through manipulation of macroH2A isoforms, we further demonstrate that macroH2A2 is the predominant barrier to reprogramming. In particular, we find macroH2A isoforms to be highly enriched at target genes of the K27me3 demethylase, Utx, which are reactivated early in iPS reprogramming", "MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency." ], "exact_answer": "no", "type": "yesno", "id": "58ab1f6c9ef3c34033000002", "snippets": [ { "offsetInBeginSection": 268, "offsetInEndSection": 393, "text": "Through manipulation of macroH2A isoforms, we further demonstrate that macroH2A2 is the predominant barrier to reprogramming.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463008", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 691, "text": "In particular, we find macroH2A isoforms to be highly enriched at target genes of the K27me3 demethylase, Utx, which are reactivated early in iPS reprogramming", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463008", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1121, "text": " Therefore, we propose that macroH2A isoforms provide a redundant silencing layer or terminal differentiation 'lock' at critical pluripotency genes that presents as an epigenetic barrier when differentiated cells are challenged to reprogram.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Histone variant macroH2A confers resistance to nuclear reprogramming", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21552206", "endSection": "title" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1051, "text": "Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21552206", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 758, "text": "We highlight the role of macroH2A in the establishment and maintenance of differentiated states and we discuss its still poorly recognized function in transcriptional activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22449192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077180", "endSection": "title" }, { "offsetInBeginSection": 603, "offsetInEndSection": 836, "text": "MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077180", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1083, "text": "Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077180", "endSection": "abstract" }, { "offsetInBeginSection": 1326, "offsetInEndSection": 1455, "text": "In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to na\u00efve pluripotency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Macro histone variants are critical for the differentiation of human pluripotent cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23595991", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 356, "text": "Here we show that the knockdown of macro histone variants impaired the in vitro and in vivo differentiation of human pluripotent cells, likely through defects in the silencing of pluripotency-related genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23595991", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 982, "text": "Furthermore, male and female mH2A-deficient ESCs proliferate normally under pluripotency culture conditions, and respond to several standard differentiation procedures efficiently.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21738686", "endSection": "abstract" } ] }, { "body": "Which disease is associated with mutations in SLC40A1 gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21175851", "http://www.ncbi.nlm.nih.gov/pubmed/27896572", "http://www.ncbi.nlm.nih.gov/pubmed/17540536", "http://www.ncbi.nlm.nih.gov/pubmed/21199650", "http://www.ncbi.nlm.nih.gov/pubmed/25744502", "http://www.ncbi.nlm.nih.gov/pubmed/22408404", "http://www.ncbi.nlm.nih.gov/pubmed/16351644", "http://www.ncbi.nlm.nih.gov/pubmed/20648054", "http://www.ncbi.nlm.nih.gov/pubmed/20691492", "http://www.ncbi.nlm.nih.gov/pubmed/16258219", "http://www.ncbi.nlm.nih.gov/pubmed/14636642", "http://www.ncbi.nlm.nih.gov/pubmed/19907151", "http://www.ncbi.nlm.nih.gov/pubmed/17997113", "http://www.ncbi.nlm.nih.gov/pubmed/21411349", "http://www.ncbi.nlm.nih.gov/pubmed/19937651", "http://www.ncbi.nlm.nih.gov/pubmed/27170390", "http://www.ncbi.nlm.nih.gov/pubmed/23943237", "http://www.ncbi.nlm.nih.gov/pubmed/24714983", "http://www.ncbi.nlm.nih.gov/pubmed/26059880", "http://www.ncbi.nlm.nih.gov/pubmed/24644245", "http://www.ncbi.nlm.nih.gov/pubmed/19342478", "http://www.ncbi.nlm.nih.gov/pubmed/22890139", "http://www.ncbi.nlm.nih.gov/pubmed/22297252", "http://www.ncbi.nlm.nih.gov/pubmed/17373275", "http://www.ncbi.nlm.nih.gov/pubmed/15692071", "http://www.ncbi.nlm.nih.gov/pubmed/22584997" ], "ideal_answer": [ "Mutations in the SLC40A1 gene, which encodes the cellular iron exporter ferroportin, are associated with the autosomal dominant hemochromatosis type 4 or Ferroportin disease. The patients characteristically have hyperferritinemia and iron overload." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.uniprot.org/uniprot/S40A1_DANRE", "http://www.uniprot.org/uniprot/S40A1_RAT", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.uniprot.org/uniprot/S40A1_HUMAN" ], "type": "summary", "id": "58bd6c5802b8c60953000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Ferroportin disease is a rare type of autosomal dominantly inherited hemochromatosis caused with mutations in the ferroportin gene (SLC40A1). The patients characteristically have hyperferritinemia but normal transferin saturations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25744502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059880", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Here we report the case of a 69-year-old Chinese Han woman who presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia and high transferrin saturation. Subsequent genetic analyses identified a novel heterozygous mutation (p.Cys326Phe) in the SLC40A1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "A novel mutation in the SLC40A1 gene associated with reduced iron export in vitro.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24644245", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Ferroportin disease is an inherited disorder of iron metabolism and is caused by mutations in the ferroportin gene (SLC40A1). We present a patient with hyperferritinemia, iron overload in the liver with reticuloendothelial distribution and also in the spleen, and under treatment with erythropheresis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24644245", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1037, "text": "These findings and the iron overload phenotype of the patient suggest that the novel mutation c.386T>C (p.L129P) in the SLC40A1 gene has incomplete penetrance and causes the classical form of ferroportin disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24644245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "Ferroportin (FPN) mediates iron export from cells and this function is modulated by serum hepcidin. Mutations in the FPN gene (SLC40A1) lead to autosomal dominant iron overload diseases related either to loss or to gain of function, and usually characterized by normal or low transferrin saturation versus elevated transferrin saturation, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23943237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 501, "text": "Hemochromatosis type 4 is a rare form of primary iron overload transmitted as an autosomal dominant trait caused by mutations in the gene encoding the iron transport protein ferroportin 1 (SLC40A1). SLC40A1 mutations fall into two functional categories (loss- versus gain-of-function) underlying two distinct clinical entities (hemochromatosis type 4A versus type 4B). However, the vast majority of SLC40A1 mutations are rare missense variations, with only a few showing strong evidence of causality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24714983", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 274, "text": "p.C282Y mutation and rare variants in the HFE gene have been associated with hereditary hemochromatosis (HH). HH is also caused by mutations in other genes, such as the hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21411349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175851", "endSection": "title" }, { "offsetInBeginSection": 19, "offsetInEndSection": 239, "text": "Ferroportin disease is characterized by iron overload. It has an autosomal-dominant pattern of inheritance and has been associated with mutations in the SLC40A1 gene, which encodes the cellular iron exporter ferroportin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199650", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 335, "text": "Mutations in the SLC40A1 gene, which encodes ferroportin, are associated with autosomal dominant hemochromatosis. Ferroportin is inhibited directly by hepcidin, a key iron-regulatory peptide, and functional consequences of SLC40A1 mutations account for observed phenotypic differences in patients with ferroportin disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19937651", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 618, "text": "The entire coding sequence of the SLC40A1 gene was sequenced in a pedigree, presenting with autosomal dominant hyperferritinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19937651", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1097, "text": "A novel SLC40A1 mutation p.R489K segregated with iron overload in a family with clinical and histopathological signs of macrophage-type ferroportin disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19937651", "endSection": "abstract" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1881, "text": "We report a novel pathological SLC40A1 variant associated with abnormal cell surface expression of ferroportin due to intracellular retention of the mutant protein. These findings predict macrophage-type ferroportin disease, the phenotype observed in this kindred. Study of the molecular cell biology of ferroportin and its mutants is key to understanding the pathogenesis of this increasingly recognized form of hemochromatosis, which responds poorly to conventional therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19937651", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 386, "text": "Classical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "Mutations in the SLC40A1 gene result in a dominant genetic disorder [ferroportin disease; hereditary hemochromatosis type (HH) IV], characterized by iron overload with two different clinical manifestations, normal transferrin saturation with macrophage iron accumulation (the most prevalent type) or high transferrin saturation with hepatocyte iron accumulation (classical hemochromatosis phenotype).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17997113", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 316, "text": "SLC40A1 gene mutations are associated with an autosomal type of genetic iron overload described as haemochromatosis type 4, or HFE4 (Online Mendelian Inheritance in Man number 606069), or ferroportin disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16351644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Ferroportin disease is an inherited disorder of iron metabolism and is caused by mutations in the ferroportin gene (SLC40A1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24644245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Mutations in the SLC40A1 gene, which encodes ferroportin, are associated with autosomal dominant hemochromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19937651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "A Japanese family with ferroportin disease caused by a novel mutation of SLC40A1 gene: hyperferritinemia associated with a relatively low transferrin saturation of iron.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258219", "endSection": "title" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1031, "text": "These findings and the iron overload phenotype of the patient suggest that the novel mutation c.386T>C (p.L129P) in the SLC40A1 gene has incomplete penetrance and causes the classical form of ferroportin disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24644245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "UNLABELLED: Mutations in the SLC40A1 gene, which encodes ferroportin, are associated with autosomal dominant hemochromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19937651", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1374, "text": "This deletion affects not only COL3A1 but also 21 other known genes (GULP1, DIRC1, COL5A2, WDR75, SLC40A1, ASNSD1, ANKAR, OSGEPL1, ORMDL1, LOC100129592, PMS1, MSTN, C2orf88, HIBCH, INPP1, MFSD6, TMEM194B, NAB1, GLS, STAT1, and STAT4), mutations in three of which (COL5A2, SLC40A1, and MSTN) have also been associated with an autosomal dominant disorder (EDS classical type, hemochromatosis type 4, and muscle hypertrophy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20648054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Analysis of SLC40A1 gene at the mRNA level reveals rapidly the causative mutations in patients with hereditary hemochromatosis type IV.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17997113", "endSection": "title" }, { "offsetInBeginSection": 384, "offsetInEndSection": 618, "text": "The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175851", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 316, "text": "SLC40A1 gene mutations are associated with an autosomal type of genetic iron overload described as haemochromatosis type 4, or HFE4 (Online Mendelian Inheritance in Man number 606069), or ferroportin disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16351644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "A Japanese family with ferroportin disease caused by a novel mutation of SLC40A1 gene: hyperferritinemia associated with a relatively low transferrin saturation of iron", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258219", "endSection": "title" }, { "offsetInBeginSection": 109, "offsetInEndSection": 318, "text": "SLC40A1 gene mutations are associated with an autosomal type of genetic iron overload described as haemochromatosis type 4, or HFE4 (Online Mendelian Inheritance in Man number 606069), or ferroportin disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16351644", "endSection": "abstract" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1412, "text": "The proposed procedure would facilitate the wide-range molecular analysis of the SLC40A1 gene, contributing to better understanding the pathogenesis of the ferroportin disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17997113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "Mutations in the SLC40A1 gene result in a dominant genetic disorder [ferroportin disease; hereditary hemochromatosis type (HH) IV], characterized by iron overload with two different clinical manifestations, normal transferrin saturation with macrophage iron accumulation (the most prevalent type) or high transferrin saturation with hepatocyte iron accumulation (classical hemochromatosis phenotype). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17997113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Type IV hemochromatosis is associated with dominant mutations in the SLC40A1 gene encoding ferroportin (FPN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15692071", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 220, "text": "It has an autosomal-dominant pattern of inheritance and has been associated with mutations in the SLC40A1 gene, which encodes the cellular iron exporter ferroportin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21199650", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 317, "text": "SLC40A1 gene mutations are associated with an autosomal type of genetic iron overload described as haemochromatosis type 4, or HFE4 (Online Mendelian Inheritance in Man number 606069), or ferroportin disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16351644", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 373, "text": "It includes hereditary hemochromatosis related to mutations of other genes, ferroportin disease (also known as hemochromatosis type 4), and entities associated with specific clinical manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17540536", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1229, "text": "Ferroportin disease is a special dominantly inherited clinical form of iron overload due to mutations of the SLC40A1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17540536", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1246, "text": "Ferroportin disease represents a protean genetic condition in which the different SLC40A1 mutations appear to be responsible for phenotypic variability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16351644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059880", "endSection": "title" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1038, "text": "These findings and the iron overload phenotype of the patient suggest that the novel mutation c.386T>C (p.L129P) in the SLC40A1 gene has incomplete penetrance and causes the classical form of ferroportin disease..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24644245", "endSection": "abstract" } ] }, { "body": "Could divalent metal transporter 1 deficiency lead to anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11090085", "http://www.ncbi.nlm.nih.gov/pubmed/25562168", "http://www.ncbi.nlm.nih.gov/pubmed/10751401", "http://www.ncbi.nlm.nih.gov/pubmed/15024413", "http://www.ncbi.nlm.nih.gov/pubmed/20336479", "http://www.ncbi.nlm.nih.gov/pubmed/15736955", "http://www.ncbi.nlm.nih.gov/pubmed/22580996", "http://www.ncbi.nlm.nih.gov/pubmed/27331785", "http://www.ncbi.nlm.nih.gov/pubmed/26294671", "http://www.ncbi.nlm.nih.gov/pubmed/16085548", "http://www.ncbi.nlm.nih.gov/pubmed/26047847" ], "ideal_answer": [ "Yes, divalent metal transporter 1 (DMT1) deficiency could result in anemia, as DMT1 is a major iron transporter required for iron absorption and erythropoiesis. DMT1 deficiency impairs erythroid differentiation and induces apoptosis of erythroid cells." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:11758", "http://amigo.geneontology.org/amigo/term/GO:0070838", "http://www.disease-ontology.org/api/metadata/DOID:2355", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018798", "http://www.disease-ontology.org/api/metadata/DOID:13121", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000740" ], "type": "yesno", "id": "58bd672d02b8c60953000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The divalent metal transporter 1 (DMT1) is a major iron transporter required for iron absorption and erythropoiesis. Loss of DMT1 function results in microcytic anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27331785", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 891, "text": "Dysfunction of human DMT1 is associated with several pathologies such as iron deficiency anemia hemochromatosis, Parkinson's disease and Alzheimer's disease, as well as colorectal cancer and esophageal adenocarcinoma, making DMT1 an attractive target for drug discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26047847", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 233, "text": "Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. We have previously shown that DMT1 deficiency impairs erythroid differentiation and induces apoptosis of erythroid cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25562168", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1516, "text": "We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25562168", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 217, "text": "Hypochromic microcytic anemia associated with ineffective erythropoiesis caused by recessive mutations in divalent metal transporter 1 (DMT1) can be improved with high-dose erythropoietin supplementation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22580996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "Belgrade rats exhibit microcytic, hypochromic anemia and systemic iron deficiency due to a glycine-to-arginine mutation at residue 185 in a metal ion transporter of a divalent metal transporter/divalent cation transporter/solute carrier 11 group A member 2 or 3 (DMT1/DCT1/SLC11A2), a member of the natural-resistance-associated macrophage protein (Nramp) family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15736955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25562168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Belgrade rats exhibit microcytic, hypochromic anemia and systemic iron deficiency due to a glycine-to-arginine mutation at residue 185 in a metal ion transporter of a divalent metal transporter/divalent cation transporter/solute carrier 11 group A member 2 or 3 (DMT1/DCT1/SLC11A2), a member of the natural-resistance-associated macrophage protein (Nramp) family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15736955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "BACKGROUND/AIMS: Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25562168", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 652, "text": "Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed to either bleomycin or saline via intratracheal instillation and the resultant lung injury was compared. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20336479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25562168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The divalent metal transporter 1 (DMT1) is a major iron transporter required for iron absorption and erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27331785", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 819, "text": "This mutation severely impairs the iron transport capability of DMT1, leading to systemic iron deficiency and anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15024413", "endSection": "abstract" } ] }, { "body": "Does the hERG gene code for a protein which is part of a sodium channel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26363003", "http://www.ncbi.nlm.nih.gov/pubmed/24475291", "http://www.ncbi.nlm.nih.gov/pubmed/18250496", "http://www.ncbi.nlm.nih.gov/pubmed/14975928", "http://www.ncbi.nlm.nih.gov/pubmed/25498859", "http://www.ncbi.nlm.nih.gov/pubmed/8521555", "http://www.ncbi.nlm.nih.gov/pubmed/25247487", "http://www.ncbi.nlm.nih.gov/pubmed/17882949", "http://www.ncbi.nlm.nih.gov/pubmed/16244363", "http://www.ncbi.nlm.nih.gov/pubmed/9556090", "http://www.ncbi.nlm.nih.gov/pubmed/19139152", "http://www.ncbi.nlm.nih.gov/pubmed/25218469", "http://www.ncbi.nlm.nih.gov/pubmed/24154981", "http://www.ncbi.nlm.nih.gov/pubmed/8873679", "http://www.ncbi.nlm.nih.gov/pubmed/10613047", "http://www.ncbi.nlm.nih.gov/pubmed/23103450", "http://www.ncbi.nlm.nih.gov/pubmed/12142119", "http://www.ncbi.nlm.nih.gov/pubmed/8995352", "http://www.ncbi.nlm.nih.gov/pubmed/24642409", "http://www.ncbi.nlm.nih.gov/pubmed/16472284", "http://www.ncbi.nlm.nih.gov/pubmed/16967046", "http://www.ncbi.nlm.nih.gov/pubmed/12063277", "http://www.ncbi.nlm.nih.gov/pubmed/17311278", "http://www.ncbi.nlm.nih.gov/pubmed/10816797", "http://www.ncbi.nlm.nih.gov/pubmed/26775140", "http://www.ncbi.nlm.nih.gov/pubmed/24045971", "http://www.ncbi.nlm.nih.gov/pubmed/26659724", "http://www.ncbi.nlm.nih.gov/pubmed/26519040", "http://www.ncbi.nlm.nih.gov/pubmed/8587608", "http://www.ncbi.nlm.nih.gov/pubmed/23792956", "http://www.ncbi.nlm.nih.gov/pubmed/9272507", "http://www.ncbi.nlm.nih.gov/pubmed/10531299", "http://www.ncbi.nlm.nih.gov/pubmed/9570196", "http://www.ncbi.nlm.nih.gov/pubmed/18617000", "http://www.ncbi.nlm.nih.gov/pubmed/9272155", "http://www.ncbi.nlm.nih.gov/pubmed/10483966" ], "ideal_answer": [ "The hERG AKA Human ether-a-go-go-related gene coded for a protein subunit of a potassium channel that conducts delayed rectifier K(+) current" ], "exact_answer": "no", "type": "yesno", "id": "58bdc76102b8c60953000013", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 115, "text": " The human ether-\u00e0-go-go-related gene (hERG 1a) potassium channel is critical for cardiac repolarization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26775140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Human ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K(+) current. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26659724", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1187, "text": "The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10613047", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 705, "text": "The molecular basis of inherited disorders caused by a mutation in either the gene coding for a particular potassium channel called HERG-or another gene, SCN5A, which codes for the sodium channel and disruption of which results in a loss of inactivation of the Na+ current.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12142119", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1426, "text": "Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10613047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8587608", "endSection": "abstract" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1612, "text": "Therefore, matrine and oxymatrine may have the potential to cure LQT2 as a potassium channel activator by promoting hERG channel activation and increasing hERG channel expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23103450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The human delta1261 mutation of the HERG potassium channel results in a truncated protein that contains a subunit interaction domain and decreases the channel expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8995352", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "HERG (human eag-related gene) encodes an inward-rectifier potassium channel formed by the assembly of four subunits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8995352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The human ether-?-go-go-related gene (HERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel in the heart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12063277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The human ether-a-go-go-related gene (hERG) encodes the rapidly activating, delayed rectifier potassium channel (IKr) important for cardiac repolarization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23103450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Role of glycosylation in cell surface expression and stability of HERG potassium channels.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12063277", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The human ERG protein (HERG or Kv 11.1) encoded by the human ether-a-go-go-related gene (herg) is the pore-forming subunit of the cardiac delayed rectifier potassium current (IKr) responsible for action potential (AP) repolarization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24154981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Human ether-a-go-go related gene (herg) encoding HERG K(+) channel has been demonstrated in many previous studies with its association to cell cycle progression and growth in tumor cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25247487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8587608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16967046", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "OBJECTIVES: The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12142119", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 477, "text": "The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16472284", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1192, "text": "The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10613047", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1264, "text": "All code for subunits of sodium or potassium channels: two a subunits of the potassium channels (QVLQT1 for LQT1, HERG for LQT2), the a subunit of the sodium channel INa (SCN5A for LQT3), and two regulatory subunits of potassium channels (KCNE1 for LQT5 regulating the KvLQT1 channel and MiRP1 regulating HERG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10816797", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 563, "text": "The corresponding genes code for potassium channels KVLQT1 (LQT1) and HERG (LQT2) and the sodium channel SCN5A (LQT3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9272155", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 709, "text": "The molecular basis of inherited disorders caused by a mutation in either the gene coding for a particular potassium channel called HERG-or another gene, SCN5A, which codes for the sodium channel and disruption of which results in a loss of inactivation of the Na+ current.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250496", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1449, "text": "There may also be correlation between the strength of binding of the medicinal substance to the potassium channel coded by the HERG gene and prolongation of the QT interval.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250496", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 723, "text": "We demonstrate that the mRNA 3'UTR of ppk29 affects neuronal firing rates and associated heat-induced seizures by acting as a natural antisense transcript (NAT) that regulates the neuronal mRNA levels of seizure (sei), the Drosophila homolog of the human Ether-\u00e0-go-go Related Gene (hERG) potassium channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24642409", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1432, "text": "Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10613047", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 903, "text": "Among the congenital forms, particularly interest is focused on the potassium channel coded by the HERG gene located on chromosome 7 and with a key role in the normal electric cardiac activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250496", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 531, "text": "By employing heterologous expression and making comparisons to cells expressing wild-type human-ether-a-go-go-related protein (HERG), a potassium channel that contributes to I(Kr) current in ventricular cardiomyocytes, we demonstrate activation of an elevated endoplasmic reticulum (ER) stress response by the mutant I593R HERG potassium channel implicated in long QT syndrome type 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16244363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10531299", "endSection": "title" }, { "offsetInBeginSection": 493, "offsetInEndSection": 603, "text": "Mutations in the human ether-\u00e0-go-go-related gene (HERG), which encodes a delayed-rectifier potassium channel,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873679", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 413, "text": "s HERG and KvLQT1 potassium channel genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9272507", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 771, "text": "HERG encodes the cardiac I(Kr) potassium channel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9556090", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 239, "text": "block of the cardiac potassium channel human ether-\u00e0-go-go-related gene (hERG) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19139152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "The human ether-a-go-go-related gene (hERG) encodes the pore-forming \u03b1-subunit of the rapidly activating delayed rectifier K(+) channel in the heart, which plays a critical role in cardiac action potential repolarization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23792956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Effects of donepezil on hERG potassium channels.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25498859", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Human ether-a-go-go related-gene K\u207a channels (hERG) participate in the regulation of tumor cell proliferation and apoptosis. HERG channel activity is up-regulated by growth factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24475291", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 45, "text": " hERG potassium channels", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045971", "endSection": "title" }, { "offsetInBeginSection": 161, "offsetInEndSection": 185, "text": "HERG, a K+ channel gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8521555", "endSection": "abstract" } ] }, { "body": "Is lenvatinib effective for renal cell carcinoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27467136", "http://www.ncbi.nlm.nih.gov/pubmed/27267515", "http://www.ncbi.nlm.nih.gov/pubmed/24190702", "http://www.ncbi.nlm.nih.gov/pubmed/27690664", "http://www.ncbi.nlm.nih.gov/pubmed/27047959", "http://www.ncbi.nlm.nih.gov/pubmed/24387233", "http://www.ncbi.nlm.nih.gov/pubmed/26482279", "http://www.ncbi.nlm.nih.gov/pubmed/27339111", "http://www.ncbi.nlm.nih.gov/pubmed/27621699" ], "ideal_answer": [ "Yes, combination of lenvatinib and everolimus is approved to treat advanced or metastatic renal cell carcinoma." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002292", "http://www.disease-ontology.org/api/metadata/DOID:4450", "http://www.disease-ontology.org/api/metadata/DOID:4451" ], "type": "yesno", "id": "589a245778275d0c4a000024", "snippets": [ { "offsetInBeginSection": 221, "offsetInEndSection": 406, "text": "However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27047959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The FDA has approved the combination of lenvatinib and everolimus to treat advanced or metastatic renal cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27267515", "endSection": "abstract" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1642, "text": "Moreover, a recent Phase II study demonstrated a significant benefit for the second-line combination treatment with everolimus plus lenvatinib (a novel TKI) in terms of progression-free survival and overall survival compared to the single-agent everolimus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621699", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 1030, "text": "We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690664", "endSection": "abstract" }, { "offsetInBeginSection": 2654, "offsetInEndSection": 2878, "text": "INTERPRETATION: Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26482279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27339111", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27339111", "endSection": "title" } ] }, { "body": "Which proteins form part of the NRD complex in S. cerevisiae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9804427", "http://www.ncbi.nlm.nih.gov/pubmed/21211720", "http://www.ncbi.nlm.nih.gov/pubmed/25877920", "http://www.ncbi.nlm.nih.gov/pubmed/10545197" ], "ideal_answer": [ "The purification of an ATR complex allowed identification of chromodomain-helicase-DNA-binding protein 4 (CHD4) as an ATR-associated protein by tandem mass spectrometric sequencing. CHD4 (also called Mi-2beta) is a component of a histone-deacetylase-2 (HDAC2)-containing complex, the nucleosome remodeling and deacetylating (NRD) complex. Endogenous ATR, CHD4, and HDAC2 are shown to coimmunoprecipitate, and ATR and HDAC2 coelute through two biochemical purification steps. Other members of the NRD complex, HDAC1, MTA1, and MTA2, are also detectable in ATR immunoprecipitates. Sen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termination through the action of its C-terminal domain (CTD)-interacting domain (CID)." ], "exact_answer": [ [ "Chd2" ], [ "Chd4" ], [ "Hdac2" ], [ "Mta1" ], [ "Mta2" ], [ "Sen1" ], [ "Pcf11" ] ], "type": "list", "id": "58adb9919ef3c34033000004", "snippets": [ { "offsetInBeginSection": 1007, "offsetInEndSection": 1314, "text": "This activity is derived from the CHD3 and CHD4 proteins which contain helicase/ATPase domains found in SWI2-related chromatin remodelling factors, and facilitates the deacetylation of oligonucleosomal histones in vitro. We refer to this complex as the nucleosome remodelling and deacetylating (NRD) complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9804427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545197", "endSection": "title" }, { "offsetInBeginSection": 265, "offsetInEndSection": 602, "text": "The purification of an ATR complex allowed identification of chromodomain-helicase-DNA-binding protein 4 (CHD4) as an ATR-associated protein by tandem mass spectrometric sequencing. CHD4 (also called Mi-2beta) is a component of a histone-deacetylase-2 (HDAC2)-containing complex, the nucleosome remodeling and deacetylating (NRD) complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545197", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 843, "text": "Endogenous ATR, CHD4, and HDAC2 are shown to coimmunoprecipitate, and ATR and HDAC2 coelute through two biochemical purification steps. Other members of the NRD complex, HDAC1, MTA1, and MTA2, are also detectable in ATR immunoprecipitates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Sen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211720", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 401, "text": "We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termination through the action of its C-terminal domain (CTD)-interacting domain (CID).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25877920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25877920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Sen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211720", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 601, "text": "CHD4 (also called Mi-2beta) is a component of a histone-deacetylase-2 (HDAC2)-containing complex, the nucleosome remodeling and deacetylating (NRD) complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545197", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 839, "text": "Other members of the NRD complex, HDAC1, MTA1, and MTA2, are also detectable in ATR immunoprecipitates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25877920", "endSection": "abstract" } ] }, { "body": "Which R / bioconductor package is used for performing SNP enrichment analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26685307" ], "ideal_answer": [ "traseR is an easy-to-use R Bioconductor package that performs enrichment analyses of trait-associated SNPs in arbitrary genomic intervals with flexible options, including testing method, type of background and inclusion of SNPs in LD." ], "exact_answer": [ "traseR" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000704" ], "type": "factoid", "id": "587e3129c32c812009000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "traseR: an R package for performing trait-associated SNP enrichment analysis in genomic intervals", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "title" }, { "offsetInBeginSection": 668, "offsetInEndSection": 916, "text": "Here, we present traseR, an easy-to-use R Bioconductor package that performs enrichment analyses of trait-associated SNPs in arbitrary genomic intervals with flexible options, including testing method, type of background and inclusion of SNPs in LD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 916, "text": "we present traseR, an easy-to-use R Bioconductor package that performs enrichment analyses of trait-associated SNPs in arbitrary genomic intervals with flexible options, including testing method, type of background and inclusion of SNPs in LD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 901, "text": "Here, we present traseR, an easy-to-use R Bioconductor package that performs enrichment analyses of trait-associated SNPs in arbitrary genomic intervals with flexible options, including testing method, type of background and inclusion of SNPs in LD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "traseR: an R package for performing trait-associated SNP enrichment analysis in genomic intervals.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "traseR: an R package for performing trait-associated SNP enrichment analysis in genomic intervals.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "title" }, { "offsetInBeginSection": 656, "offsetInEndSection": 905, "text": "Here, we present traseR, an easy-to-use R Bioconductor package that performs enrichment analyses of trait-associated SNPs in arbitrary genomic intervals with flexible options, including testing method, type of background and inclusion of SNPs in LD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1107, "text": "The traseR R package preloaded with up-to-date collection of trait-associated SNPs are freely available in Bioconductor zhaohui.qin@emory.edu Supplementary data are available at Bioinformatics online..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26685307", "endSection": "abstract" } ] }, { "body": "Does HuR bind to the untranslated regions (UTRs) of mRNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27941336", "http://www.ncbi.nlm.nih.gov/pubmed/23389914", "http://www.ncbi.nlm.nih.gov/pubmed/25841336", "http://www.ncbi.nlm.nih.gov/pubmed/25265983", "http://www.ncbi.nlm.nih.gov/pubmed/23312841", "http://www.ncbi.nlm.nih.gov/pubmed/24687854" ], "ideal_answer": [ "Yes, the RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target transcripts, thereby protecting them against degradation." ], "exact_answer": "yes", "type": "yesno", "id": "58ce69cd1f5fb2b734000003", "snippets": [ { "offsetInBeginSection": 115, "offsetInEndSection": 347, "text": "HuR is also overexpressed during tumourigenesis and is abnormally present within the cytoplasm, where it binds to AU-rich elements in the 3'UTRs of target mRNA and post-transcriptionally regulates the expression of its target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27941336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Human antigen R (HuR) is a ubiquitous 32 kDa protein comprising three RNA Recognition Motifs (RRMs), whose main function is to bind Adenylate and uridylate Rich Elements (AREs) in 3' UnTranslated Regions (UTRs) of mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25841336", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 147, "text": "Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein that modulates gene expression at the post-transcriptional level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25265983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target transcripts, thereby protecting them against degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24687854", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 812, "text": "ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312841", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 381, "text": "This is achieved by altered expression of the proteins TTP and HuR, which bind 3' untranslated region (UTR) elements in cancer-related genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23389914", "endSection": "abstract" } ] }, { "body": "Describe Exploding head syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24703829", "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "http://www.ncbi.nlm.nih.gov/pubmed/20112796", "http://www.ncbi.nlm.nih.gov/pubmed/1896728", "http://www.ncbi.nlm.nih.gov/pubmed/20726288", "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "http://www.ncbi.nlm.nih.gov/pubmed/11309216", "http://www.ncbi.nlm.nih.gov/pubmed/2030791", "http://www.ncbi.nlm.nih.gov/pubmed/2769286", "http://www.ncbi.nlm.nih.gov/pubmed/23467433" ], "ideal_answer": [ "Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "summary", "id": "588f9756ed9bbee70d000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Exploding head syndrome is characterized by the perception of loud noises during sleep-wake or wake-sleep transitions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24703829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "BACKGROUND: Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "INTRODUCTION: Exploding head syndrome (EHS) is a rare parasomnia in which affected individuals awaken from sleep with the sensation of a loud bang.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23467433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Exploding head syndrome (EHS) attacks are characterized by the sensation of sudden loud banging noises, and are occasionally accompanied by the sensation of a flash light.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20112796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake.We present six new cases extending the clinical experience with the syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Exploding head syndrome (EHS) is a rare parasomnia in which affected individuals awaken from sleep with the sensation of a loud bang", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23467433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Exploding head syndrome (EHS) attacks are characterized by the sensation of sudden loud banging noises, and are occasionally accompanied by the sensation of a flash light. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20112796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake.We present six new cases extending the clinical experience with the syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "abstract" } ] }, { "body": "Is H4K20 methylation associated with DNA replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24049080", "http://www.ncbi.nlm.nih.gov/pubmed/24013172", "http://www.ncbi.nlm.nih.gov/pubmed/23152447", "http://www.ncbi.nlm.nih.gov/pubmed/20735237", "http://www.ncbi.nlm.nih.gov/pubmed/26598646", "http://www.ncbi.nlm.nih.gov/pubmed/23345616", "http://www.ncbi.nlm.nih.gov/pubmed/23924899", "http://www.ncbi.nlm.nih.gov/pubmed/27131378", "http://www.ncbi.nlm.nih.gov/pubmed/27268234", "http://www.ncbi.nlm.nih.gov/pubmed/23754963" ], "ideal_answer": [ "We employed genetic, cytological, and genomic approaches to better understand the role of PR-Set7 and H4K20 methylation in regulating DNA replication and genome stability in Drosophila cells. Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes. The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing. \u00a9 2016 by The American Society for Biochemistry and Molecular Biology, Inc.\u00a9 2016 by The American Society for Biochemistry and Molecular Biology, Inc. 0.05).These findings may indicate that intradermal antigens used in this study were more effective in inducing the Koebner phenomenon than injury alone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9169322", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 390, "text": "RESULTS: Striae are documented to cause Koebner phenomenon in patients with preexisting vitiligo, psoriasis and lichen planus, the three conditions where 'true kobenerisation' has been suggested according to Boyd and Nelder classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19489859", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 1021, "text": "According to the presence of Koebner phenomenon they were divided in two groups, one with positive and the other with negative Koebner phenomenon which presented the control group at the same time.RESULTS AND DISCUSSION: The Koebner reaction is often thought to be more frequent in actively spreading, severe psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11089373", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 312, "text": "We describe a case of concurrent lichen planus and sarcoidosis in the auditory canal, which represents an unusual manifestation of the Koebner phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18499373", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 999, "text": "According to the presence of Koebner phenomenon they were divided into two groups, 20 patients with positive and 40 patients with negative Koebner reaction, who were the control group at the same time.RESULTS AND DISCUSSION: 95% of patients treated with PUVA, were cleared of psoriatic changes in the Koebner positive, as well as in the Koebner negative group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10748764", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 374, "text": "Striae are documented to cause Koebner phenomenon in patients with preexisting vitiligo, psoriasis and lichen planus, the three conditions where 'true kobenerisation' has been suggested according to Boyd and Nelder classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19489859", "endSection": "abstract" } ] }, { "body": "Is there a role of proton beam therapy in medulloblastoma treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16165914", "http://www.ncbi.nlm.nih.gov/pubmed/9231669", "http://www.ncbi.nlm.nih.gov/pubmed/25415685", "http://www.ncbi.nlm.nih.gov/pubmed/24105630", "http://www.ncbi.nlm.nih.gov/pubmed/9240650", "http://www.ncbi.nlm.nih.gov/pubmed/15637691", "http://www.ncbi.nlm.nih.gov/pubmed/26548600", "http://www.ncbi.nlm.nih.gov/pubmed/25927402", "http://www.ncbi.nlm.nih.gov/pubmed/16332594", "http://www.ncbi.nlm.nih.gov/pubmed/9112448", "http://www.ncbi.nlm.nih.gov/pubmed/12377335", "http://www.ncbi.nlm.nih.gov/pubmed/23322160", "http://www.ncbi.nlm.nih.gov/pubmed/22553304", "http://www.ncbi.nlm.nih.gov/pubmed/1310964", "http://www.ncbi.nlm.nih.gov/pubmed/16168831", "http://www.ncbi.nlm.nih.gov/pubmed/24187330", "http://www.ncbi.nlm.nih.gov/pubmed/23433794", "http://www.ncbi.nlm.nih.gov/pubmed/25403752", "http://www.ncbi.nlm.nih.gov/pubmed/15701271" ], "ideal_answer": [ "Yes, proton beam therapy is used for treatment of medulloblastoma." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4058240", "http://www.disease-ontology.org/api/metadata/DOID:0050902", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061766", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011878", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008527" ], "type": "yesno", "id": "58850ac7e56acf5176000012", "snippets": [ { "offsetInBeginSection": 746, "offsetInEndSection": 952, "text": "All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25927402", "endSection": "abstract" }, { "offsetInBeginSection": 1872, "offsetInEndSection": 2212, "text": "There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24187330", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24187330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Evaluation of permanent alopecia in pediatric medulloblastoma patients treated with proton radiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25403752", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "BACKGROUND: To precisely calculate skin dose and thus to evaluate the relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with proton beams.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25403752", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1314, "text": "CONCLUSIONS: Our results based on 12 patients provide a relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with protons. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25403752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23433794", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "PURPOSE: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23433794", "endSection": "abstract" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1358, "text": "CONCLUSIONS: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23433794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553304", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "OBJECTIVE: To improve medulloblastoma proton therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24187330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24187330", "endSection": "abstract" }, { "offsetInBeginSection": 1311, "offsetInEndSection": 1528, "text": "All patients completed therapy without interruption.Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9240650", "endSection": "title" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1569, "text": "For 6 MV x-rays > 60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9240650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9231669", "endSection": "title" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1515, "text": "This review describes the role of radiation in general and proton therapy in particular for the treatment of medulloblastoma, central nervous system primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and the recently described embryonal tumor with multilayered rosettes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25415685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701271", "endSection": "title" }, { "offsetInBeginSection": 2674, "offsetInEndSection": 3031, "text": "Intensity-modulated radiotherapy did show more bladder dose reduction than the other techniques in pelvic sarcoma irradiation.CONCLUSIONS: In the diseases studied, using various techniques of 3D-CRT, electrons, IMRT, and protons, protons are most optimal in treating retinoblastomas, medulloblastomas (posterior fossa and craniospinal), and pelvic sarcomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16168831", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1619, "text": "For 6 MV x-rays>60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.CONCLUSION: The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9240650", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 872, "text": "In medulloblastoma, three posterior fossa irradiation techniques were analyzed: 3D-CRT, IMRT, and protons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16168831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9240650", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9231669", "endSection": "title" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1573, "text": "The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9240650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24187330", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553304", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "To improve medulloblastoma proton therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553304", "endSection": "abstract" }, { "offsetInBeginSection": 1366, "offsetInEndSection": 1532, "text": "Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15701271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16168831", "endSection": "title" } ] }, { "body": "What is the function of the DGAT1 gene product?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17592768", "http://www.ncbi.nlm.nih.gov/pubmed/24676595", "http://www.ncbi.nlm.nih.gov/pubmed/21264296", "http://www.ncbi.nlm.nih.gov/pubmed/15834126", "http://www.ncbi.nlm.nih.gov/pubmed/15797871", "http://www.ncbi.nlm.nih.gov/pubmed/23539897", "http://www.ncbi.nlm.nih.gov/pubmed/25687632", "http://www.ncbi.nlm.nih.gov/pubmed/16534144", "http://www.ncbi.nlm.nih.gov/pubmed/12825687", "http://www.ncbi.nlm.nih.gov/pubmed/12407108", "http://www.ncbi.nlm.nih.gov/pubmed/11481333", "http://www.ncbi.nlm.nih.gov/pubmed/23055800", "http://www.ncbi.nlm.nih.gov/pubmed/16130466", "http://www.ncbi.nlm.nih.gov/pubmed/20876538" ], "ideal_answer": [ "Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in the acyl-CoA-dependent triacylglycerol biosynthesis", "Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in the acyl-CoA-dependent triacylglycerol biosynthesis. . . . . ", "diacylglycerol acyltransferase 1 (dgat1) catalyzes the final step in the acyl-coa-dependent triacylglycerol biosynthesis.", "Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in the acyl-CoA-dependent triacylglycerol biosynthesis, the enzyme catalyzes a key step in lipid biosynthesis.", "Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in the acyl-CoA-dependent triacylglycerol biosynthesis." ], "concepts": [ "http://www.uniprot.org/uniprot/DGAT1_DICDI", "http://www.uniprot.org/uniprot/DGAT1_ARATH", "http://www.uniprot.org/uniprot/DGAT1_MOUSE", "http://www.uniprot.org/uniprot/DGAT1_HUMAN", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051048", "http://www.uniprot.org/uniprot/DGAT1_CHLAE", "http://www.uniprot.org/uniprot/DGAT1_BOVIN" ], "type": "summary", "id": "58cbf1f402b8c60953000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in the acyl-CoA-dependent triacylglycerol biosynthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687632", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 283, "text": "This genomic area includes the DGAT1 gene, which encodes acyl-CoA:diacylglycerol acyltransferase 1, the key enzyme of triglyceride biosynthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16534144", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 222, "text": "Diacylglycerol acyltransferase (DGAT1) is considered the key enzyme in controlling the rate of synthesis of triglycerides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17592768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) catalyzes the final step of triglyceride synthesis in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12407108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Diacylglycerol O-acyltransferase 1 (DGAT1) is a microsomal enzyme that catalyzes the final step of triglyceride synthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23055800", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 342, "text": "The enzyme 1,2-acylCoA:diacylglyceroltransferase-1 (DGAT1) esterifies a fatty acyl-CoA on DAG to form TAG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21264296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "DGAT1 is a microsomal enzyme that catalyses the final step in triglycerides synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16130466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Diacylglycerol-O-acyltransferase (DGAT1) gene encodes the rate-limiting enzyme of triglyceride synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24676595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Acyl CoA:diacylglycerol acyltransferase (DGAT) is an integral membrane protein of the endoplasmic reticulum that catalyzes the synthesis of triacylglycerols", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20876538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The final step of triacylglycerol biosynthesis is catalyzed by acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15834126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Triacylglycerol (TAG) is the major carbon storage reserve in oilseeds such as Arabidopsis. Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyses the final step of the TAG synthesis pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12825687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Acyl-CoA:diacylglycerol acyltransferases (DGATs) catalyze the last step in triglyceride (TG) synthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15797871", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 997, "text": " This study further confirmed the importance of DGAT1 in triglyceride synthesis in bovine mammary tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Acyl CoA:diacylgycerol acyltransferase (EC; DGAT) catalyzes the final step in the production of triacylglycerol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11481333", "endSection": "abstract" } ] }, { "body": "Which histone mutation is associated with gliomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26957305", "http://www.ncbi.nlm.nih.gov/pubmed/24242757", "http://www.ncbi.nlm.nih.gov/pubmed/27034984", "http://www.ncbi.nlm.nih.gov/pubmed/27701736", "http://www.ncbi.nlm.nih.gov/pubmed/26297251", "http://www.ncbi.nlm.nih.gov/pubmed/27392443", "http://www.ncbi.nlm.nih.gov/pubmed/26517431", "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "http://www.ncbi.nlm.nih.gov/pubmed/24285547", "http://www.ncbi.nlm.nih.gov/pubmed/23539183", "http://www.ncbi.nlm.nih.gov/pubmed/25170156", "http://www.ncbi.nlm.nih.gov/pubmed/25401693", "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "http://www.ncbi.nlm.nih.gov/pubmed/25773741" ], "ideal_answer": [ "Pediatric central nervous system tumors are the most common solid tumor of childhood. Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3.", "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. Genome-wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes.", "some of these molecular changes with clinicopathological utility have been used for the first time in the most recent edition of the world health organization (who) classification of cns tumours to define entities like ependymoma, rela fusion-positive or diffuse midline glioma, h3 k27m-mutant.", "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3" ], "exact_answer": [ "K27M in H3.3" ], "type": "factoid", "id": "58bac71222d3005309000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 546, "text": "We show that H3.3K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 730, "text": "Some of these molecular changes with clinicopathological utility have been used for the first time in the most recent edition of the World Health Organization (WHO) classification of CNS tumours to define entities like ependymoma, RELA fusion-positive or diffuse midline glioma, H3 K27M-mutant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27701736", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 828, "text": "The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27034984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "title" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1444, "text": "In this series, histone H3-K27M mutation was mutually exclusive with IDH1 mutation and EGFR amplification, rarely co-occurred with BRAF-V600E mutation, and was commonly associated with p53 overexpression, ATRX loss (except in pontine gliomas), and monosomy 10.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26517431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27392443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Diffuse Midline Gliomas with Histone H3-K27M Mutation: A Series of 47 Cases Assessing the Spectrum of Morphologic Variation and Associated Genetic Alterations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26517431", "endSection": "title" }, { "offsetInBeginSection": 392, "offsetInEndSection": 479, "text": "Here, we describe a series of 47 diffuse midline gliomas with histone H3-K27M mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26517431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25170156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Sequencing of pediatric gliomas has identified missense mutations Lys27Met (K27M) and Gly34Arg/Val (G34R/V) in genes encoding histone H3.3 (H3F3A) and H3.1 (HIST3H1B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25401693", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 454, "text": "We report that human diffuse intrinsic pontine gliomas (DIPGs) containing the K27M mutation display significantly lower overall amounts of H3 with trimethylated lysine 27 (H3K27me3) and that histone H3K27M transgenes are sufficient to reduce the amounts of H3K27me3 in vitro and in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539183", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1739, "text": "In particular, histone genes (H3F3A (K27M) , HIST1H3B (K27M) ) mutations are frequent in adult DIBG whereas IDH1 (R132H) mutations are rare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24242757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "title" }, { "offsetInBeginSection": 214, "offsetInEndSection": 290, "text": "The role of the H3.3K27M mutation in tumorigenesis is not fully understood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "title" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1524, "text": "In this series, histone H3-K27M mutation was mutually exclusive with IDH1 mutation and EGFR amplification, rarely co-occurred with BRAF-V600E mutation, and was commonly associated with p53 overexpression, ATRX loss (except in pontine gliomas), and monosomy 10. \u00a9 2015 International Society of Neuropathology.\u00a9 2015", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26253404", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1087, "text": "In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26253404", "endSection": "abstract" }, { "offsetInBeginSection": 1310, "offsetInEndSection": 1532, "text": "We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations. \u00a9 2015.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26253404", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1088, "text": "In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26253404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Meis1 coordinates a network of genes implicated in eye development and microphthalmia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26253404", "endSection": "title" } ] }, { "body": "Can Pentraxin 3 predict outcomes of sepsis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15977234", "http://www.ncbi.nlm.nih.gov/pubmed/25001601", "http://www.ncbi.nlm.nih.gov/pubmed/21423699", "http://www.ncbi.nlm.nih.gov/pubmed/11445697", "http://www.ncbi.nlm.nih.gov/pubmed/27864924", "http://www.ncbi.nlm.nih.gov/pubmed/26872435", "http://www.ncbi.nlm.nih.gov/pubmed/22278372", "http://www.ncbi.nlm.nih.gov/pubmed/24958171", "http://www.ncbi.nlm.nih.gov/pubmed/23341967", "http://www.ncbi.nlm.nih.gov/pubmed/20119647", "http://www.ncbi.nlm.nih.gov/pubmed/26982005", "http://www.ncbi.nlm.nih.gov/pubmed/26717657", "http://www.ncbi.nlm.nih.gov/pubmed/25227610", "http://www.ncbi.nlm.nih.gov/pubmed/25530683", "http://www.ncbi.nlm.nih.gov/pubmed/25048752", "http://www.ncbi.nlm.nih.gov/pubmed/25591437", "http://www.ncbi.nlm.nih.gov/pubmed/24039869" ], "ideal_answer": [ "Yes, Pentraxin 3 s an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018805", "http://www.biosemantics.org/jochem#4264880", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000066891" ], "type": "yesno", "id": "5890eb22621ea6ff7e000006", "snippets": [ { "offsetInBeginSection": 1447, "offsetInEndSection": 1708, "text": "As compared with low serum PTX3and sTWEAK cases, cirrhotic patients with high serum PTX3/sTWEAK levels a have higher probability of new severe infections, severe sepsis, septic shock, type 1 hepatorenal syndrome, in-hospital, and 3-month follow-up mortalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26872435", "endSection": "abstract" }, { "offsetInBeginSection": 1350, "offsetInEndSection": 1543, "text": "Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25048752", "endSection": "abstract" }, { "offsetInBeginSection": 3688, "offsetInEndSection": 4106, "text": "In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).CONCLUSION: The PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26717657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Severe Acinetobacter baumannii sepsis is associated with elevation of pentraxin 3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25001601", "endSection": "title" }, { "offsetInBeginSection": 1636, "offsetInEndSection": 1755, "text": "Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25001601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20119647", "endSection": "title" }, { "offsetInBeginSection": 231, "offsetInEndSection": 332, "text": "PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20119647", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1645, "text": "CONCLUSIONS: Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20119647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27864924", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Pentraxin 3: an immune modulator of infection and useful marker for disease severity assessment in sepsis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26982005", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24958171", "endSection": "title" }, { "offsetInBeginSection": 270, "offsetInEndSection": 504, "text": "The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15977234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11445697", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23341967", "endSection": "title" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1278, "text": "In addition, high levels of PTX3 were associated with unfavorable outcome.CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11445697", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 323, "text": "PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20119647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24958171", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20119647", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23341967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The proteomic profile of circulating pentraxin 3 (PTX3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22278372", "endSection": "title" } ] }, { "body": "Which polymerase transcribes pri-miRNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18042145", "http://www.ncbi.nlm.nih.gov/pubmed/26473486", "http://www.ncbi.nlm.nih.gov/pubmed/18829588", "http://www.ncbi.nlm.nih.gov/pubmed/26119101", "http://www.ncbi.nlm.nih.gov/pubmed/20144951", "http://www.ncbi.nlm.nih.gov/pubmed/21702984", "http://www.ncbi.nlm.nih.gov/pubmed/15372072", "http://www.ncbi.nlm.nih.gov/pubmed/26149087", "http://www.ncbi.nlm.nih.gov/pubmed/21685453", "http://www.ncbi.nlm.nih.gov/pubmed/15589161", "http://www.ncbi.nlm.nih.gov/pubmed/15525708", "http://www.ncbi.nlm.nih.gov/pubmed/21178961", "http://www.ncbi.nlm.nih.gov/pubmed/19398578", "http://www.ncbi.nlm.nih.gov/pubmed/25730776", "http://www.ncbi.nlm.nih.gov/pubmed/20129062", "http://www.ncbi.nlm.nih.gov/pubmed/22499686", "http://www.ncbi.nlm.nih.gov/pubmed/20655920" ], "ideal_answer": [ "Recent evidence indicates that miRNA genes are transcribed by RNA polymerase II (Pol II) we have established a robust in vivo system in which pri-miRNA is transcribed by RNAP II and processed to pre-miRNA in HeLa cell nuclear extracts.", "Previous studies in vivo reported that processing of primary microRNA (pri-miRNA) is coupled to transcription by RNA polymerase II (RNAP II) and can occur co-transcriptionally. ", "The non-protein-encoding pri-miRNAs are synthesized by RNA polymerase II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail.", " Analogously to mRNAs, the non-protein-encoding pri-miRNAs are synthesized by RNA polymerase II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail. Recent evidence indicates that miRNA genes are transcribed by RNA polymerase II (Pol II)", "Previous studies in vivo reported that processing of primary microRNA (pri-miRNA) is coupled to transcription by RNA polymerase II (RNAP II) and can occur co-transcriptionally. we have established a robust in vivo system in which pri-miRNA is transcribed by RNAP II and processed to pre-miRNA in HeLa cell nuclear extracts.", "Because the transcripts of most miRNA genes are the products of type-II RNA polymerase, pri-miRNA has a poly(A) tail and appears in expressed sequence tags (EST). Analogously to mRNAs, the non-protein-encoding pri-miRNAs are synthesized by RNA polymerase II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail." ], "exact_answer": [ "RNA polymerase II", "RNAPII" ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:1902893", "http://amigo.geneontology.org/amigo/term/GO:1902895", "http://amigo.geneontology.org/amigo/term/GO:1902894", "http://amigo.geneontology.org/amigo/term/GO:0061614", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012319" ], "type": "factoid", "id": "589d965a78275d0c4a000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Previous studies in vivo reported that processing of primary microRNA (pri-miRNA) is coupled to transcription by RNA polymerase II (RNAP II) and can occur co-transcriptionally. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149087", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 328, "text": "we have established a robust in vivo system in which pri-miRNA is transcribed by RNAP II and processed to pre-miRNA in HeLa cell nuclear extracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149087", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 873, "text": "In addition, obvious enrichments of three histone modifications (H2BK5me1, H3K36me3 and H4K20me1) as well as RNA Polymerase II (RNAPII) were observed on pre-miRNA genomic sequences corresponding to the active-promoter miRNAs and expressed miRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21702984", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 413, "text": "Because the transcripts of most miRNA genes are the products of type-II RNA polymerase, pri-miRNA has a poly(A) tail and appears in expressed sequence tags (EST)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20655920", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 398, "text": "Recent evidence indicates that miRNA genes are transcribed by RNA polymerase II (Pol II)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18829588", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 688, "text": "Since Pol II transcripts are capped, we hypothesized that CBP (cap-binding protein) 20 and 80 may bind to capped primary miRNA (pri-miRNA) transcripts and play a role in their processing. Here, we show that cbp20 and cbp80 mutants have reduced miRNA levels and increased pri-miRNA levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18829588", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 299, "text": " Analogously to mRNAs, the non-protein-encoding pri-miRNAs are synthesized by RNA polymerase II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18042145", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 279, "text": "Plant miRNAs are first transcribed as stem-loop primary miRNAs (pri-miRNAs) by RNA polymerase II,then cleaved in the nucleus into mature miRNAs by Dicer-like 1 (DCL1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26473486", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 453, "text": "miRNAs are excised in a stepwise process from double-stranded RNA precursors that are embedded in long RNA polymerase II primary transcripts (pri-miRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15589161", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 795, "text": "Plant pri-miRNAs are transcribed by DNA-dependent RNA polymerase II (Pol II) and their levels are determined through transcription and degradation, whereas pri-miRNA processing is affected by its structure, splicing, alternative splicing, loading to the processor and the processor activity, which involve in many accessory proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26119101", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 716, "text": "Specifically, MHV68 miRNAs are transcribed from RNA polymerase III promoters located within adjacent viral tRNA-like sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129062", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 234, "text": "Mammalian miRNA biogenesis begins with cotranscriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25730776", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 455, "text": "miRNAs are excised in a stepwise process from double-stranded RNA precursors that are embedded in long RNA polymerase II primary transcripts (pri-miRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15589161", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Canonical primary microRNA (pri-miRNA) precursors are transcribed by RNA polymerase II and then processed by the Drosha endonuclease to generate approximately 60 nt pre-miRNA hairpins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20129062", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 751, "text": "Treatment of cells overexpressing NF90 and NF45 with an RNA polymerase II inhibitor, alpha-amanitin, did not reduce the amounts of pri-miRNAs, suggesting that the accumulation of pri-miRNAs is not due to transcriptional activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398578", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 279, "text": "Plant miRNAs are first transcribed as stem-loop primary miRNAs (pri-miRNAs) by RNA polymerase II,then cleaved in the nucleus into mature miRNAs by Dicer-like 1 (DCL1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26473486", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 797, "text": "Plant pri-miRNAs are transcribed by DNA-dependent RNA polymerase II (Pol II) and their levels are determined through transcription and degradation, whereas pri-miRNA processing is affected by its structure, splicing, alternative splicing, loading to the processor and the processor activity, which involve in many accessory proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26119101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The majority of human miRNA genes is transcribed by polymerase II and can be classified as class II genes similar to protein-coding genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20144951", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 798, "text": "Plant pri-miRNAs are transcribed by DNA-dependent RNA polymerase II (Pol II) and their levels are determined through transcription and degradation, whereas pri-miRNA processing is affected by its structure, splicing, alternative splicing, loading to the processor and the processor activity, which involve in many accessory proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26119101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "In plant, primary transcripts (pri-miRNAs) transcribed from miRNA genes by RNA polymerase II are first processed into stem-loop pre-miRNAs and further chopped into \u223c21\u2009nt long miRNAs by RNase III-like enzyme DCL1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685453", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1050, "text": "These small RNAs are first transcribed by RNA polymerase II as a primary miRNA (pri-miRNA) transcript, which is then cleaved into the precursor miRNA (pre-miRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21178961", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 381, "text": "Here we present the first direct evidence that miRNA genes are transcribed by RNA polymerase II (pol II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15372072", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 280, "text": "Plant miRNAs are first transcribed as stem-loop primary miRNAs (pri-miRNAs) by RNA polymerase II,then cleaved in the nucleus into mature miRNAs by Dicer-like 1 (DCL1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26473486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "MicroRNA genes are transcribed by RNA polymerase II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15372072", "endSection": "title" }, { "offsetInBeginSection": 177, "offsetInEndSection": 328, "text": "Here we have established a robust in vivo system in which pri-miRNA is transcribed by RNAP II and processed to pre-miRNA in HeLa cell nuclear extracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149087", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 1012, "text": "Although it is assumed that miRNA promoters are similar in structure to gene promoters, since both are transcribed by RNA polymerase II (Pol II), computational validations exhibit poor performance of gene promoter prediction methods on miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22499686", "endSection": "abstract" } ] }, { "body": "Which mutated enzyme is responsible for oculocutaneous 1 (OCA1)-type albinism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22088535", "http://www.ncbi.nlm.nih.gov/pubmed/21968110", "http://www.ncbi.nlm.nih.gov/pubmed/9170158", "http://www.ncbi.nlm.nih.gov/pubmed/8651291", "http://www.ncbi.nlm.nih.gov/pubmed/12829739", "http://www.ncbi.nlm.nih.gov/pubmed/23112997", "http://www.ncbi.nlm.nih.gov/pubmed/24934919", "http://www.ncbi.nlm.nih.gov/pubmed/11574907", "http://www.ncbi.nlm.nih.gov/pubmed/15381243", "http://www.ncbi.nlm.nih.gov/pubmed/16767664", "http://www.ncbi.nlm.nih.gov/pubmed/23242301", "http://www.ncbi.nlm.nih.gov/pubmed/27775880", "http://www.ncbi.nlm.nih.gov/pubmed/10571953", "http://www.ncbi.nlm.nih.gov/pubmed/25093188", "http://www.ncbi.nlm.nih.gov/pubmed/10713140", "http://www.ncbi.nlm.nih.gov/pubmed/16907708", "http://www.ncbi.nlm.nih.gov/pubmed/7886000", "http://www.ncbi.nlm.nih.gov/pubmed/27537549", "http://www.ncbi.nlm.nih.gov/pubmed/1905879", "http://www.ncbi.nlm.nih.gov/pubmed/24721949", "http://www.ncbi.nlm.nih.gov/pubmed/20447099", "http://www.ncbi.nlm.nih.gov/pubmed/9242509", "http://www.ncbi.nlm.nih.gov/pubmed/27829221", "http://www.ncbi.nlm.nih.gov/pubmed/11641241", "http://www.ncbi.nlm.nih.gov/pubmed/25216246", "http://www.ncbi.nlm.nih.gov/pubmed/19208379", "http://www.ncbi.nlm.nih.gov/pubmed/15146472", "http://www.ncbi.nlm.nih.gov/pubmed/22875490", "http://www.ncbi.nlm.nih.gov/pubmed/15937636", "http://www.ncbi.nlm.nih.gov/pubmed/11284711", "http://www.ncbi.nlm.nih.gov/pubmed/12753405", "http://www.ncbi.nlm.nih.gov/pubmed/17355913", "http://www.ncbi.nlm.nih.gov/pubmed/11041207", "http://www.ncbi.nlm.nih.gov/pubmed/25577957", "http://www.ncbi.nlm.nih.gov/pubmed/26763160", "http://www.ncbi.nlm.nih.gov/pubmed/15635296", "http://www.ncbi.nlm.nih.gov/pubmed/10094567", "http://www.ncbi.nlm.nih.gov/pubmed/22097729", "http://www.ncbi.nlm.nih.gov/pubmed/11153699", "http://www.ncbi.nlm.nih.gov/pubmed/25919014", "http://www.ncbi.nlm.nih.gov/pubmed/15760344", "http://www.ncbi.nlm.nih.gov/pubmed/10671066", "http://www.ncbi.nlm.nih.gov/pubmed/10671067", "http://www.ncbi.nlm.nih.gov/pubmed/24392141" ], "ideal_answer": [ "Mutations in the gene for tyrosinase (TYR), the key enzyme in melanin synthesis, are responsible for oculocutaneous 1 (OCA1)-type albinism." ], "exact_answer": [ "tyrosinase", "TYR" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050632", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016115", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000417" ], "type": "factoid", "id": "58cbb98c02b8c60953000034", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 89, "text": "An overview of oculocutaneous albinism: TYR gene mutations in five Colombian individuals", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242301", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 385, "text": "To date, 230 mutations in the TYR gene have been reported as responsible for oculocutaneus albinism type 1 worldwide. TYR gene encodes the enzyme tyrosinase involved in the metabolic pathway of melanin synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242301", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 644, "text": "Mutations were identified in the TYR gene as responsible for oculocutaneous albinism type 1 in five Colombian individuals, and a new ophthalmic system was tested that corrected visual defects and symptoms in a patient with oculocutaneous albinism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Mutations in the gene for tyrosinase, the key enzyme in melanin synthesis, are responsible for oculocutaneous albinism type 1, and more than 100 mutations of this gene have been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19208379", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 522, "text": "The Q402 allele has been associated with autosomal recessive ocular albinism when it is in trans with a tyrosinase gene mutation associated with oculocutaneous albinism type 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19208379", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 503, "text": "The disruption of tyrosinase trafficking occurs at the level of the endoplasmic reticulum (ER) in OCA1 and OCA3, but at the post-Golgi level in OCA2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12829739", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 308, "text": "Mutations at a single N-glycosylation sequon of tyrosinase have been reported to be responsible for oculocutaneous albinism type IA in humans, characterized by inactive tyrosinase and the total absence of pigmentation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10713140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10671066", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 582, "text": "Mutations in the human tyrosinase gene produce tyrosinase-related oculocutaneous albinism (OCA1, MIM #203100). Tyrosinase is a copper containing enzyme and is responsible for catalyzing the rate limiting step in melanin biosynthesis, the hydroxylation of tyrosine to dopaquinone. We report 13 new mutations in the tyrosinase gene associated with OCA1A (without pigment) and OCA1B (with pigment) including 9 missense mutations (H19Q, R521, R77C, G97R, C289R, L312V, P313R, F340L and H404P), two nonsense mutations (W80X and R116X) and two frameshift mutations (53delG and 223 delG). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10671066", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 671, "text": "Mutations of the TYR gene lead to Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism in humans (OMIM accession number 203100).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Mutations of the tyrosinase gene associated with a partial or complete loss of enzymatic activity are responsible for tyrosinase related oculocutaneous albinism (OCA1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7886000", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 767, "text": "Oculocutaneous albinism type 1 (OCA1), resulting from mutations of the tyrosinase gene, is genetically and biochemically the best understood type of albinism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12753405", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 945, "text": "Mutations in six genes have been reported to be responsible for different types of oculocutaneous and ocular albinism, including the tyrosinase gene (TYR) and OCA1 (MIM# 203100), the OCA2 gene and OCA2 (MIM# 203200), the tyrosinase-related protein-1 gene (TYRP1) and OCA3 (MIM# 203290), the HPS gene and Hermansky-Pudlak syndrome (MIM# 203300), the CHS gene (CHS1), and Chediak-Higashi syndrome (MIM# 214500), and the X-linked ocular albinism gene and OA1 (MIM#300500).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10094567", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 348, "text": "Defects in the tyrosinase gene (TYR) cause a common type of OCA, known as oculocutaneous albinism type 1 (OCA1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16907708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Oculocutaneous albinism (OCA) in man may be caused by mutations within the tyrosinase gene (TYR) resulting in OCA1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15146472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216246", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "BACKGROUND: Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 469, "text": "Mutation analysis and prenatal gene diagnosis for the mutated tyrosinase (TYR) gene in two families with oculocutaneous albinism type I (OCA1).To define the fetus genotypes and gene mutation sites, the PCR and sequencing techniques were applied to amplify and analyze the regions of exon, exon-intron and promoter of TYR gene in probands and their parents of 2 families.The patient or proband of family 1 showed as a compound heterozygote with mutants R278X and 929insC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16767664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Mutations in the gene for tyrosinase, the key enzyme in melanin synthesis, are responsible for oculocutaneous albinism type 1, and more than 100 mutations of this gene have been identified", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19208379", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 752, "text": "TYR gene encodes the enzyme tyrosinase involved in the metabolic pathway of melanin synthesis.Mutations were identified in the TYR gene as responsible for oculocutaneous albinism type 1 in five Colombian individuals, and a new ophthalmic system was tested that corrected visual defects and symptoms in a patient with oculocutaneous albinism.Samples were taken from 5 individuals, four of whom belong to a single family, along with a fifth individual not related to the family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15937636", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 385, "text": "Disrupting mutations in the tyrosinase (TYR) gene are known to cause recessive albinisms in humans (oculocutaneous albinism Type 1; OCA1) and other species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26763160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "To explore the patients genotypes and the mutation spectrum of Tyrosinase (TYR) gene and the effects on protein structure and function in oculocutaneous albinism type 1 (OCA1).The polymerase chain reaction (PCR) and sequencing techniques were applied to amplify and analyze the regions of exon, exonintron and promoter of TYR gene of 15 OCA1 probands and some of their parents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22097729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15635296", "endSection": "title" }, { "offsetInBeginSection": 529, "offsetInEndSection": 677, "text": "Mutations of the TYR gene lead to Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism in humans (OMIM accession number 203100). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Mutations of the tyrosinase gene associated with a partial or complete loss of enzymatic activity are responsible for tyrosinase related oculocutaneous albinism (OCA1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7886000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15937636", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 629, "text": "OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11574907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Tyrosinase (EC 1.14.18.1) is a copper-containing enzyme that catalyzes several reactions in the biosynthesis of melanin pigments and is deficient in patients with type I oculocutaneous albinism (OCA1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9242509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15937636", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 676, "text": "Mutations of the TYR gene lead to Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism in humans (OMIM accession number 203100).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153699", "endSection": "abstract" }, { "offsetInBeginSection": 63, "offsetInEndSection": 224, "text": "In humans mutations in the TYR gene are associated with type 1 oculocutaneous albinism (OCA1) that leads to reduced or absent pigmentation of skin, hair and eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15760344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disease resulting from mutations of the tyrosinase gene (TYR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11284711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392141", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 948, "text": "Mutations in six genes have been reported to be responsible for different types of oculocutaneous and ocular albinism, including the tyrosinase gene (TYR) and OCA1 (MIM# 203100), the OCA2 gene and OCA2 (MIM# 203200), the tyrosinase-related protein-1 gene (TYRP1) and OCA3 (MIM# 203290), the HPS gene and Hermansky-Pudlak syndrome (MIM# 203300), the CHS gene (CHS1), and Chediak-Higashi syndrome (MIM# 214500), and the X-linked ocular albinism gene and OA1 (MIM#300500).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10094567", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 656, "text": "Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes.The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392141", "endSection": "abstract" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1863, "text": "The tyrosinase gene family of proteins (tyrosinase, TRP1, and TRP2) regulate the type of eumelanin synthesized and mutations affecting them result in OCA1, OCA3, and slaty (in the murine system), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9170158", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15635296", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Mutation analysis and prenatal gene diagnosis for the mutated tyrosinase (TYR) gene in two families with oculocutaneous albinism type I (OCA1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16767664", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 772, "text": "Oculocutaneous albinism type 1 (OCA1), resulting from mutations of the tyrosinase gene, is genetically and biochemically the best understood type of albinism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12753405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216246", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Oculocutaneous albinism Type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27775880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The mutation of the tyrosinase (TYR) gene results in oculocutaneous albinism type 1 (OCA1), an autosomal recessive genetic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22088535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The tyrosinase gene and oculocutaneous albinism type 1 (OCA1): A model for understanding the molecular biology of melanin formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11041207", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15635296", "endSection": "title" } ] }, { "body": "Please list 2 treatments for a torn rotator cuff", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22004636", "http://www.ncbi.nlm.nih.gov/pubmed/26912284", "http://www.ncbi.nlm.nih.gov/pubmed/21351612", "http://www.ncbi.nlm.nih.gov/pubmed/20621893", "http://www.ncbi.nlm.nih.gov/pubmed/26847487", "http://www.ncbi.nlm.nih.gov/pubmed/26564215", "http://www.ncbi.nlm.nih.gov/pubmed/8496210", "http://www.ncbi.nlm.nih.gov/pubmed/27157656", "http://www.ncbi.nlm.nih.gov/pubmed/26254089" ], "ideal_answer": [ "to compare clinical outcomes between conventional en masse repair and separate double-layer double-row repair for the treatment of delaminated rotator cuff tears.", "Surgical repair earlier or later than 3 months after injury may result in similar outcomes and patient satisfaction." ], "exact_answer": [ [ "early surgery" ], [ "later surgery(3 months after injury)" ], [ "en masse repair" ], [ "double-layer double-row repair" ], [ "arthroscopic" ], [ "open" ], [ "knotless transosseous-equivalent" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:12702", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000070656", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000070636", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017006" ], "type": "list", "id": "58c99acf02b8c60953000028", "snippets": [ { "offsetInBeginSection": 408, "offsetInEndSection": 569, "text": "To compare clinical outcomes between conventional en masse repair and separate double-layer double-row repair for the treatment of delaminated rotator cuff tears", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26912284", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 594, "text": " To systematically review and evaluate the effectiveness of grafts in the augmentation of large-to-massive rotator cuff repairs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26847487", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 150, "text": "To evaluate the effectiveness of arthroscopic debridement (DB), partial (PR), and complete repair (CR) for massive rotator cuff tears (mRCT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26254089", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 163, "text": "The purpose was to investigate whether surgical repair earlier or later than 3\u00a0months after injury may result in similar outcomes and patient satisfaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26564215", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 155, "text": "double-row (DR) and knotless transosseous-equivalent (KL-TOE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27157656", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 255, "text": " arthroscopic subacromial decompression and rotator-cuff debridement; the other comparable group of 23 patients had open repair and acromioplasty", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8496210", "endSection": "abstract" } ] }, { "body": "What is the role of Laser Interstitial Thermal Therapy in glioma treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26722845", "http://www.ncbi.nlm.nih.gov/pubmed/26384598", "http://www.ncbi.nlm.nih.gov/pubmed/27861323", "http://www.ncbi.nlm.nih.gov/pubmed/27838155", "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "http://www.ncbi.nlm.nih.gov/pubmed/27690658", "http://www.ncbi.nlm.nih.gov/pubmed/22044371", "http://www.ncbi.nlm.nih.gov/pubmed/25727222", "http://www.ncbi.nlm.nih.gov/pubmed/26113069", "http://www.ncbi.nlm.nih.gov/pubmed/18838327", "http://www.ncbi.nlm.nih.gov/pubmed/27861322", "http://www.ncbi.nlm.nih.gov/pubmed/24056317", "http://www.ncbi.nlm.nih.gov/pubmed/24810945", "http://www.ncbi.nlm.nih.gov/pubmed/24994550", "http://www.ncbi.nlm.nih.gov/pubmed/27659837", "http://www.ncbi.nlm.nih.gov/pubmed/27690657", "http://www.ncbi.nlm.nih.gov/pubmed/25434378" ], "ideal_answer": [ "Laser Interstitial Thermal Therapy (LITT) is used in treatment of gliomas. LITT can be used effectively for treatment of difficult-to-access high-grade gliomas. More complete coverage of tumor improves progression free survival which can be translated as the extent of resection concept for surgery." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053685", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005910" ], "type": "summary", "id": "5890f4ab621ea6ff7e000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "OBJECTIVE MR-guided laser-induced thermal therapy (MRgLITT) can be used to treat intracranial tumors, epilepsy, and chronic pain syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26722845", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1346, "text": "Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690658", "endSection": "abstract" }, { "offsetInBeginSection": 1878, "offsetInEndSection": 2087, "text": "CONCLUSIONS Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690658", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 739, "text": "MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26113069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The role of laser interstitial thermal therapy in enhancing progression-free survival of difficult-to-access high-grade gliomas: a multicenter study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24810945", "endSection": "title" }, { "offsetInBeginSection": 262, "offsetInEndSection": 594, "text": "We report our multicenter results of laser interstitial thermal therapy (LITT) in DTA-HGGs. We retrospectively reviewed 34 consecutive DTA-HGG patients (24 glioblastoma, 10 anaplastic) who underwent LITT at Cleveland Clinic, Washington University, and Wake Forest University (May 2011-December 2012) using the NeuroBlate(\u00ae) System. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24810945", "endSection": "abstract" }, { "offsetInBeginSection": 1484, "offsetInEndSection": 1669, "text": "LITT can be used effectively for treatment of DTA-HGGs. More complete coverage of tumor by TDT lines improves PFS which can be translated as the extent of resection concept for surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24810945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Stereotactic laser ablation of high-grade gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434378", "endSection": "title" }, { "offsetInBeginSection": 171, "offsetInEndSection": 438, "text": "Recent advances in intraoperative imaging have spurred the use of stereotactic laser ablation (laser interstitial thermal therapy [LITT]) for intracranial lesions. Among other targets, laser ablation has been used in the focal treatment of high-grade gliomas (HGGs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma: clinical article.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "OBJECT: Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 1779, "offsetInEndSection": 1943, "text": "CONCLUSIONS: NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 1118, "text": "Ongoing researches concern the adjunction of local treatments within the surgical field (photodynamic therapy, chemotherapy, convection immunotherapy...), but also the development of minimal invasive procedures (radiosurgery, high intensity focalized ultrasounds, laser interstitial thermal therapy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18838327", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 1066, "text": "Current commercially available LITT systems have been used for the treatment of neurosurgical soft-tissue lesions, including difficult to access brain tumors, malignant gliomas, and radiosurgery-resistant metastases, as well as for the ablation of such lesions as epileptogenic foci and radiation necrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25727222", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 403, "text": " The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 734, "text": "MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26113069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "MRI-guided laser interstitial thermal therapy for the treatment of low-grade gliomas in children: a case-series review, description of the current technologies and perspectives.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27659837", "endSection": "title" }, { "offsetInBeginSection": 577, "offsetInEndSection": 737, "text": "MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26113069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Thermal ablation (radiofrequency, microwave, cryosurgery, laser interstitial thermal therapy) is being used more frequently as a local treatment of secondary but also primary cancers and benign lesions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26384598", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The role of laser interstitial thermal therapy in enhancing progression-free survival of difficult-to-access high-grade gliomas: a multicenter study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24810945", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Current Applications of MRI-Guided Laser Interstitial Thermal Therapy in the Treatment of Brain Neoplasms and Epilepsy: A Radiologic and Neurosurgical Overview", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26113069", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is a minimally invasive treatment modality with recent increasing use to ablate brain tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24994550", "endSection": "abstract" }, { "offsetInBeginSection": 1755, "offsetInEndSection": 1871, "text": "Further study is needed to assess the role of laser-induced thermal therapy for the treatment of intracranial tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22044371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "OBJECT: Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 1726, "offsetInEndSection": 1942, "text": "Three had Grade 3 adverse events at the highest dose.CONCLUSIONS: NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The role of laser interstitial thermal therapy in enhancing progression-free survival of difficult-to-access high-grade gliomas: a multicenter study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24810945", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Stereotactic Laser Interstitial Thermal Therapy for Recurrent High-Grade Gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27861323", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "MRI-guided laser interstitial thermal therapy for the treatment of low-grade gliomas in children: a case-series review, description of the current technologies and perspectives.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27659837", "endSection": "title" }, { "offsetInBeginSection": 577, "offsetInEndSection": 738, "text": "MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26113069", "endSection": "abstract" }, { "offsetInBeginSection": 1756, "offsetInEndSection": 1906, "text": "NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Laser interstitial thermal therapy followed by minimal-access transsulcal resection for the treatment of large and difficult to access brain tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690658", "endSection": "title" } ] }, { "body": "Which protein mediates the replacement of H2A by H2A.Z in the yeast Saccharomyces cerevisiae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20711347", "http://www.ncbi.nlm.nih.gov/pubmed/15045029", "http://www.ncbi.nlm.nih.gov/pubmed/23816883", "http://www.ncbi.nlm.nih.gov/pubmed/17470967", "http://www.ncbi.nlm.nih.gov/pubmed/21111233", "http://www.ncbi.nlm.nih.gov/pubmed/23580526", "http://www.ncbi.nlm.nih.gov/pubmed/18726008", "http://www.ncbi.nlm.nih.gov/pubmed/22910211", "http://www.ncbi.nlm.nih.gov/pubmed/19910462", "http://www.ncbi.nlm.nih.gov/pubmed/24507717", "http://www.ncbi.nlm.nih.gov/pubmed/17289584", "http://www.ncbi.nlm.nih.gov/pubmed/19966225", "http://www.ncbi.nlm.nih.gov/pubmed/16299513", "http://www.ncbi.nlm.nih.gov/pubmed/27463665", "http://www.ncbi.nlm.nih.gov/pubmed/26116819", "http://www.ncbi.nlm.nih.gov/pubmed/17142478", "http://www.ncbi.nlm.nih.gov/pubmed/19088068" ], "ideal_answer": [ "Saccharomyces cerevisiae Swr1, a Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit chromatin remodeling enzyme, called the SWR1 complex, that efficiently replaces conventional histone H2A in nucleosomes with histone H2A.Z. We identified a complex containing 13 different polypeptides associated with a soluble pool of H2A.Z in Saccharomyces cerevisiae.", "The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. The SWR1 complex replaces the canonical histone H2A with the variant H2A.Z (Htz1 in yeast) at specific chromatin regions.", "The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z.", "The chromatin remodeler SWR1 mediates site-specific incorporation of H2A.Z by a multi-step histone replacement reaction, evicting histone H2A-H2B from the canonical nucleosome and depositing the H2A.Z-H2B dimer", "The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. Saccharomyces cerevisiae Swr1, a Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit chromatin remodeling enzyme, called the SWR1 complex, that efficiently replaces conventional histone H2A in nucleosomes with histone H2A.Z." ], "exact_answer": [ "SWR1" ], "type": "factoid", "id": "58a6db8660087bc10a00002c", "snippets": [ { "offsetInBeginSection": 125, "offsetInEndSection": 335, "text": "The chromatin remodeler SWR1 mediates site-specific incorporation of H2A.Z by a multi-step histone replacement reaction, evicting histone H2A-H2B from the canonical nucleosome and depositing the H2A.Z-H2B dimer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26116819", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 333, "text": "he multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24507717", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 899, "text": "Our results show that the Swr1-Z domain can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form the nucleosome by a histone chaperone mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24507717", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 801, "text": "H2A.Z is deposited into chromatin by the SWR1 complex and is subject to acetylation of its four N-terminal tail lysine residues by the NuA4 and SAGA histone acetyltransferase complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23816883", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 236, "text": "H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes that catalyze the nucleosomal exchange of canonical H2A with H2A.Z. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580526", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 423, "text": "Saccharomyces cerevisiae Swr1, a Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit chromatin remodeling enzyme, called the SWR1 complex, that efficiently replaces conventional histone H2A in nucleosomes with histone H2A.Z.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22910211", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 886, "text": "The system demonstrates ATP- and SWR1-complex-dependent replacement of histone H2A for histone H2A.Z on a preassembled nucleosome array. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22910211", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 414, "text": "We identified a complex containing 13 different polypeptides associated with a soluble pool of H2A.Z in Saccharomyces cerevisiae. This complex was designated SWR1-Com in reference to the Swr1p subunit, a Swi2/Snf2-paralog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15045029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The SWR1 complex replaces the canonical histone H2A with the variant H2A.Z (Htz1 in yeast) at specific chromatin regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20711347", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 302, "text": "In Saccharomyces cerevisiae, deposition of histone H2AZ is mediated by the multiprotein SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16299513", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 286, "text": "In Saccharomyces cerevisiae, chromatin deposition of histone H2AZ is mediated by the fourteen-subunit SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19088068", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 245, "text": "This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21111233", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 424, "text": "Saccharomyces cerevisiae Swr1, a Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit chromatin remodeling enzyme, called the SWR1 complex, that efficiently replaces conventional histone H2A in nucleosomes with histone H2A.Z. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22910211", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 287, "text": "In Saccharomyces cerevisiae, chromatin deposition of histone H2AZ is mediated by the fourteen-subunit SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19088068", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 303, "text": "In Saccharomyces cerevisiae, deposition of histone H2AZ is mediated by the multiprotein SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16299513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The Swc4p protein, encoded by an essential gene, is shared by two chromatin-remodeling complexes in Saccharomyces cerevisiae cells: NuA4 (nucleosome acetyltransferase of H4) and SWR1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18726008", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 368, "text": "The Saccharomyces cerevisiae protein Yaf9 is a subunit of both the essential histone acetyltransferase complex NuA4 and the ATP-dependent chromatin remodeling complex SWR1-C, which deposits histone variant H2A.Z into euchromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19966225", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 398, "text": "Here, we identify and characterize SERRATED LEAVES AND EARLY FLOWERING (SEF), an Arabidopsis (Arabidopsis thaliana) homolog of the yeast SWC6 protein, a conserved subunit of the SWR1/SRCAP complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17142478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The SWR1/SRCAP complex is a chromatin-remodeling complex that has been shown to be involved in substitution of histone H2A by the histone variant H2A.Z in yeast (Saccharomyces cerevisiae) and animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17142478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The Swc4p protein, encoded by an essential gene, is shared by two chromatin-remodeling complexes in Saccharomyces cerevisiae cells: NuA4 (nucleosome acetyltransferase of H4) and SWR1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18726008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The SWR1 complex (SWR1C) in yeast catalyzes the replacement of nucleosomal H2A with the H2AZ variant, which ensures full activation of underlying genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17470967", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1011, "text": "In addition, H2AZ, a substrate of SWR1C, interacts with both PIE1 and AtSWC2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17470967", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 243, "text": "The incorporation of H2AZ into chromatin is dependent on the SWR1 complex, which catalyses the replacement of conventional histone H2A with H2AZ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17289584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "H2A histone-fold and DNA elements in nucleosome activate SWR1-mediated H2A.Z replacement in budding yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26116819", "endSection": "title" }, { "offsetInBeginSection": 177, "offsetInEndSection": 301, "text": "They report that reversal of H2A.Z replacement is mediated by SWR1 and related INO80 on an H2A.Z nucleosome carrying H3K56Q.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27463665", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 336, "text": "The chromatin remodeler SWR1 mediates site-specific incorporation of H2A.Z by a multi-step histone replacement reaction, evicting histone H2A-H2B from the canonical nucleosome and depositing the H2A.Z-H2B dimer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26116819", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 244, "text": "This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21111233", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 473, "text": "Here, we show that the JmjC domain protein Msc1 is a novel component of the fission yeast Swr1 complex and is required for Swr1-mediated incorporation of H2A.Z into nucleosomes at gene promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19910462", "endSection": "abstract" } ] }, { "body": "Which are the key players on radial glial specification to ependymal cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26395491", "http://www.ncbi.nlm.nih.gov/pubmed/27606337" ], "ideal_answer": [ "Mcidas and GemC1/Lynkeas specify embryonic radial glial cells. Both proteins were initially described as cell cycle regulators revealing sequence similarity to Geminin. They are expressed in radial glial cells committed to the ependymal cell lineage during embryogenesis, while overexpression and knock down experiments showed that are sufficient and necessary for ependymal cell generation." ], "exact_answer": [ [ "Mcidas" ], [ "GemC1", "Lynkeas" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063928", "http://amigo.geneontology.org/amigo/term/GO:0090213", "http://amigo.geneontology.org/amigo/term/GO:0009956", "http://amigo.geneontology.org/amigo/term/GO:0021531", "http://amigo.geneontology.org/amigo/term/GO:0021861", "http://amigo.geneontology.org/amigo/term/GO:0021812" ], "type": "list", "id": "58948cb47d9090f353000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Mcidas and GemC1/Lynkeas specify embryonic radial glial cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27606337", "endSection": "title" }, { "offsetInBeginSection": 655, "offsetInEndSection": 1358, "text": "Here we discuss recent findings suggesting that 2 novel molecules, Mcidas and GemC1/Lynkeas are key players on radial glial specification to ependymal cells. Both proteins were initially described as cell cycle regulators revealing sequence similarity to Geminin. They are expressed in radial glial cells committed to the ependymal cell lineage during embryogenesis, while overexpression and knock down experiments showed that are sufficient and necessary for ependymal cell generation. We propose that Mcidas and GemC1/Lynkeas are key components of the molecular cascade that promotes radial glial cells fate commitment toward multiciliated ependymal cell lineage operating upstream of c-Myb and FoxJ1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27606337", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 809, "text": "Here we discuss recent findings suggesting that 2 novel molecules, Mcidas and GemC1/Lynkeas are key players on radial glial specification to ependymal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27606337", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 853, "text": "Overexpression and knockdown experiments show that Mcidas and GemC1 are sufficient and necessary for cell fate commitment and differentiation of radial glial cells to multiciliated ependymal cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26395491", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 812, "text": "Here we discuss recent findings suggesting that 2 novel molecules, Mcidas and GemC1/Lynkeas are key players on radial glial specification to ependymal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27606337", "endSection": "abstract" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1237, "text": "Our results suggest that Mcidas and GemC1 are key players in the generation of multiciliated ependymal cells of the adult neurogenic niche.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26395491", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1358, "text": "We propose that Mcidas and GemC1/Lynkeas are key components of the molecular cascade that promotes radial glial cells fate commitment toward multiciliated ependymal cell lineage operating upstream of c-Myb and FoxJ1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27606337", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Mcidas and GemC1 are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26395491", "endSection": "title" } ] }, { "body": "Is ocular melanosis a risk factor for uveal melanoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21670341", "http://www.ncbi.nlm.nih.gov/pubmed/12647250", "http://www.ncbi.nlm.nih.gov/pubmed/9442799", "http://www.ncbi.nlm.nih.gov/pubmed/8292886", "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "http://www.ncbi.nlm.nih.gov/pubmed/6677847", "http://www.ncbi.nlm.nih.gov/pubmed/1520683" ], "ideal_answer": [ "Yes, ocular melanosis (melanosis oculi) is a risk factor for uveal melanoma." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.disease-ontology.org/api/metadata/DOID:6566", "http://www.disease-ontology.org/api/metadata/DOID:6039", "http://www.disease-ontology.org/api/metadata/DOID:1752", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306" ], "type": "yesno", "id": "58b5320e22d3005309000002", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 201, "text": "Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 582, "text": "Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma. Ophthalmic surveillance, every 6 or 12 months is important, in patients with ocular melanocytosis for early detection of high risk diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12647250", "endSection": "abstract" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1520, "text": " One of about 400 patients with ODM followed for life is estimated to develop uveal melanoma. Excessive melanocytes in the uveal tract in ODM may provide the biologic basis for susceptibility to the development of uveal melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of uveal melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing uveal melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9442799", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 132, "text": "In the white population, an association between oculo(dermal) melanocytosis (ODM) and uveal melanoma is well recognized. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9442799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Malignant melanomas may arise in the uveal tract, the conjunctiva, the skin of the eyelid, or the orbit. Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8292886", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 323, "text": "Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8292886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Phacomatosis pigmentovascularis of cesioflammea type in 7 patients: combination of ocular pigmentation (melanocytosis or melanosis) and nevus flammeus with risk for melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21670341", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 441, "text": "In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.DISCUSSION: Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12647250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "endSection": "title" }, { "offsetInBeginSection": 105, "offsetInEndSection": 323, "text": "Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8292886", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 421, "text": "In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12647250", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 813, "text": "In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis.To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma.Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008.Enucleation, plaque radiotherapy, local resection, or thermotherapy.Metastasis and death.Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "endSection": "abstract" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1913, "text": "By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 422, "text": "In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12647250", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 324, "text": "Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8292886", "endSection": "abstract" }, { "offsetInBeginSection": 1900, "offsetInEndSection": 2077, "text": "CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1810, "text": "By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "endSection": "abstract" }, { "offsetInBeginSection": 1811, "offsetInEndSection": 1988, "text": "CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23681424", "endSection": "abstract" } ] }, { "body": "What is known about telomere length shortening and stress?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25393133", "http://www.ncbi.nlm.nih.gov/pubmed/26853993", "http://www.ncbi.nlm.nih.gov/pubmed/25070535", "http://www.ncbi.nlm.nih.gov/pubmed/26919486" ], "ideal_answer": [ "A significant relationship between more perceived stress and shorter telomere length is consistent with theoretical frameworks positing that stress induces physiological changes that result in shortened telomeres." ], "type": "summary", "id": "58cd633c02b8c6095300003a", "snippets": [ { "offsetInBeginSection": 781, "offsetInEndSection": 995, "text": "A significant relationship between more perceived stress and shorter telomere length is consistent with theoretical frameworks positing that stress induces physiological changes that result in shortened telomeres. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25393133", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 175, "text": "Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26853993", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1591, "text": "Our results support the hypothesis that depression is associated with accelerated cell aging. Future studies are required to clarify whether the association is mediated through environmental stress, and whether effective treatment can halt cell aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26919486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Telomere length, a reliable predictor of disease pathogenesis, can be affected by genetics, chronic stress and health behaviors. Cross-sectionally, highly stressed postmenopausal women have shorter telomeres, but only if they are inactive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25070535", "endSection": "abstract" } ] }, { "body": "What fruit causes Jamaican vomiting sickness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6488562", "http://www.ncbi.nlm.nih.gov/pubmed/8185109", "http://www.ncbi.nlm.nih.gov/pubmed/26324727", "http://www.ncbi.nlm.nih.gov/pubmed/23259140", "http://www.ncbi.nlm.nih.gov/pubmed/16099087", "http://www.ncbi.nlm.nih.gov/pubmed/3548729", "http://www.ncbi.nlm.nih.gov/pubmed/26328472", "http://www.ncbi.nlm.nih.gov/pubmed/25531872" ], "ideal_answer": [ "Jamaican Vomiting Sickness is caused by ingestion of the unripe arils of the Ackee fruit, its seeds and husks." ], "exact_answer": [ "Ackee fruit" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015984", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005638" ], "type": "factoid", "id": "5895f7e978275d0c4a000001", "snippets": [ { "offsetInBeginSection": 187, "offsetInEndSection": 315, "text": "The aril of the unripe fruit has high concentrations of HGA, the cause of Jamaican vomiting sickness, which is very often fatal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531872", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 315, "text": "In 1976, over 100 years after Jamaican vomiting sickness (JVS) was first reported, the cause of JVS was linked to the ingestion of the toxin hypoglycin A produced by ackee fruit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26328472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Ackee apple fruit is a native fruit to Jamaica and some parts of west Africa. Its toxicity known as \"Jamaican vomiting sickness\" dates back to the nineteenth century.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26324727", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 282, "text": "Jamaican Vomiting Sickness is caused by ingestion of the unripe arils of the Ackee fruit, its seeds and husks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "An acute illness (Jamaican vomiting sickness) which affected two adults after eating unripe ackee fruit was investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6488562", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 281, "text": "Jamaican Vomiting Sickness is caused by ingestion of the unripe arils of the Ackee fruit, its seeds and husks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259140", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 314, "text": "The aril of the unripe fruit has high concentrations of HGA, the cause of Jamaican vomiting sickness, which is very often fatal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25531872", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 313, "text": "In 1976, over 100 years after Jamaican vomiting sickness (JVS) was first reported, the cause of JVS was linked to the ingestion of the toxin hypoglycin A produced by ackee fruit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26328472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Hypoglycin A, the toxin found in the ackee fruit, has been reported in the literature as the causative agent in incidences of acute toxicity termed Jamaican vomiting sickness or toxic hypoglycemic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16099087", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 281, "text": "Jamaican Vomiting Sickness is caused by ingestion of the unripe arils of the Ackee fruit, its seeds and husks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "An acute illness (Jamaican vomiting sickness) which affected two adults after eating unripe ackee fruit was investigated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6488562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Hypoglycin A, the toxin found in the ackee fruit, has been reported in the literature as the causative agent in incidences of acute toxicity termed Jamaican vomiting sickness or toxic hypoglycemic syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16099087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Hypoglycin A, the toxin found in the ackee fruit, has been reported in the literature as the causative agent in incidences of acute toxicity termed Jamaican vomiting sickness or toxic hypoglycemic syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16099087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "An acute illness (Jamaican vomiting sickness) which affected two adults after eating unripe ackee fruit was investigated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6488562", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 314, "text": "In 1976, over 100 years after Jamaican vomiting sickness (JVS) was first reported, the cause of JVS was linked to the ingestion of the toxin hypoglycin A produced by ackee fruit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26328472", "endSection": "abstract" } ] }, { "body": "Which gene is mutated in the Karak syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16783378", "http://www.ncbi.nlm.nih.gov/pubmed/26001724", "http://www.ncbi.nlm.nih.gov/pubmed/20938027", "http://www.ncbi.nlm.nih.gov/pubmed/27884548", "http://www.ncbi.nlm.nih.gov/pubmed/18443314", "http://www.ncbi.nlm.nih.gov/pubmed/24130795" ], "ideal_answer": [ "PLA2G6 gene is mutated in the Karak syndrome." ], "exact_answer": [ "PLA2G6" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "factoid", "id": "588f9950ed9bbee70d000002", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 333, "text": "Mutations in PLA2G6 have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation type II and Karak syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26001724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Mutations in PLA2G6 gene have variable phenotypic outcome including infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, idiopathic neurodegeneration with brain iron accumulation and Karak syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24130795", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: PLA2G6 is the causative gene for infantile neuroaxonal dystrophy, neurodegeneration associated with brain iron accumulation, and Karak syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20938027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "PLA2G6 is the causative gene for infantile neuroaxonal dystrophy, neurodegeneration associated with brain iron accumulation, and Karak syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20938027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Mutations in PLA2G6 gene have variable phenotypic outcome including infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, idiopathic neurodegeneration with brain iron accumulation and Karak syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24130795", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 474, "text": "Recessively inherited mutations of the PLA2G6 gene are causative of infantile neuroaxonal dystrophy and other PLA2G6-associated neurodegeneration, which includes conditions known as atypical neuroaxonal dystrophy, Karak syndrome and early-onset dystonia-parkinsonism with cognitive impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27884548", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 333, "text": "Mutations in PLA2G6 have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation type II and Karak syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26001724", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 455, "text": "We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16783378", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 457, "text": "We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16783378", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 335, "text": "Mutations in PLA2G6 have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation type II and Karak syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26001724", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 475, "text": "Recessively inherited mutations of the PLA2G6 gene are causative of infantile neuroaxonal dystrophy and other PLA2G6-associated neurodegeneration, which includes conditions known as atypical neuroaxonal dystrophy, Karak syndrome and early-onset dystonia-parkinsonism with cognitive impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27884548", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 334, "text": "Mutations in PLA2G6 have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation type II and Karak syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26001724", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 456, "text": "We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16783378", "endSection": "abstract" } ] }, { "body": "What is LedPred?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26628586" ], "ideal_answer": [ "LedPred is an R/bioconductor package to predict regulatory sequences using support vector machines. LedPred is provided as an R/Bioconductor package connected to an online server to avoid installation of non-R software. Due to the heterogeneous CRM feature integration, LedPred excels at the prediction of regulatory sequences in Drosophila and mouse datasets compared with similar SVM-based software." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060388", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012045" ], "type": "summary", "id": "587e392d2420191125000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "LedPred: an R/bioconductor package to predict regulatory sequences using support vector machines", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "title" }, { "offsetInBeginSection": 316, "offsetInEndSection": 803, "text": "Here, we present LedPred, a flexible SVM workflow that predicts new regulatory sequences based on the annotation of known CRMs, which are associated to a large variety of feature types. LedPred is provided as an R/Bioconductor package connected to an online server to avoid installation of non-R software. Due to the heterogeneous CRM feature integration, LedPred excels at the prediction of regulatory sequences in Drosophila and mouse datasets compared with similar SVM-based software.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "LedPred: an R/bioconductor package to predict regulatory sequences using support vector machines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "title" }, { "offsetInBeginSection": 606, "offsetInEndSection": 787, "text": "Due to the heterogeneous CRM feature integration, LedPred excels at the prediction of regulatory sequences in Drosophila and mouse datasets compared with similar SVM-based software.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 487, "text": "Here, we present LedPred, a flexible SVM workflow that predicts new regulatory sequences based on the annotation of known CRMs, which are associated to a large variety of feature types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 1085, "text": "Due to the heterogeneous CRM feature integration, LedPred excels at the prediction of regulatory sequences in Drosophila and mouse datasets compared with similar SVM-based software.LedPred is available on GitHub: https://github.com/aitgon/LedPred and Bioconductor: http://bioconductor.org/packages/release/bioc/html/LedPred.html under the MIT license.aitor.gonzalez@univ-amu.frSupplementary data are available at Bioinformatics online.\u00a9 The Author 2015.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "LedPred: an R/bioconductor package to predict regulatory sequences using support vector machines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "title" }, { "offsetInBeginSection": 610, "offsetInEndSection": 791, "text": "Due to the heterogeneous CRM feature integration, LedPred excels at the prediction of regulatory sequences in Drosophila and mouse datasets compared with similar SVM-based software.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 489, "text": "Here, we present LedPred, a flexible SVM workflow that predicts new regulatory sequences based on the annotation of known CRMs, which are associated to a large variety of feature types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26628586", "endSection": "abstract" } ] }, { "body": "Is siltuximab effective for Castleman disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25310208", "http://www.ncbi.nlm.nih.gov/pubmed/26124203", "http://www.ncbi.nlm.nih.gov/pubmed/25042199", "http://www.ncbi.nlm.nih.gov/pubmed/25601959", "http://www.ncbi.nlm.nih.gov/pubmed/26327301", "http://www.ncbi.nlm.nih.gov/pubmed/25110138", "http://www.ncbi.nlm.nih.gov/pubmed/26749192", "http://www.ncbi.nlm.nih.gov/pubmed/25736164", "http://www.ncbi.nlm.nih.gov/pubmed/26634298", "http://www.ncbi.nlm.nih.gov/pubmed/25784388", "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "http://www.ncbi.nlm.nih.gov/pubmed/27152394", "http://www.ncbi.nlm.nih.gov/pubmed/25685858", "http://www.ncbi.nlm.nih.gov/pubmed/26394632", "http://www.ncbi.nlm.nih.gov/pubmed/26869762", "http://www.ncbi.nlm.nih.gov/pubmed/23659971", "http://www.ncbi.nlm.nih.gov/pubmed/25884809" ], "ideal_answer": [ "Yes, siltuximab , a chimeric human-mouse monoclonal antibody to IL6, is approved for the treatment of patients with multicentric Castleman disease who are human immunodeficiency virus negative and human herpesvirus-8 negative." ], "exact_answer": "yes", "type": "yesno", "id": "5896d3e278275d0c4a000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26634298", "endSection": "title" }, { "offsetInBeginSection": 317, "offsetInEndSection": 680, "text": "The recent approvals in North America, Europe and Brazil of siltuximab, a monoclonal antibody against IL-6, for iMCD now provide a safe and effective therapy that targets a key aspect of pathogenesis. In the first ever randomized, placebo-controlled trial in iMCD, siltuximab significantly reduced disease burden and symptoms in a large portion (34%) of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26634298", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 854, "text": "Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26749192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Emerging treatments in Castleman disease - a critical appraisal of siltuximab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26869762", "endSection": "title" }, { "offsetInBeginSection": 284, "offsetInEndSection": 793, "text": " Siltuximab, a chimeric monoclonal antibody to IL-6, has thus emerged as a promising treatment option in a disease lacking efficacious therapy. Here, we review the findings of recent studies evaluating single-agent siltuximab treatment in CD, including the first-ever randomized clinical trial in this disease. Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26869762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601959", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601959", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1757, "text": "Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "endSection": "abstract" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1744, "text": "Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Siltuximab for multicentric Castleman disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25110138", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26394632", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26124203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26327301", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659971", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26124203", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Siltuximab (Sylvant). Castleman's disease: good symptomatic efficacy in some patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27152394", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Siltuximab: a new option for the management of Castleman's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685858", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 445, "text": "PURPOSE: To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.EXPERIMENTAL DESIGN: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Dose selection of siltuximab for multicentric Castleman's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25784388", "endSection": "title" }, { "offsetInBeginSection": 243, "offsetInEndSection": 690, "text": "Here, modeling and simulation of the pharmacokinetic (PK)/pharmacodynamic (PD) relationship between siltuximab and CRP were used to support dose selection for multicentric Castleman's disease (CD).METHODS: PK/PD modeling was applied to explore the relationship between siltuximab PK and CRP suppression following intravenous siltuximab infusion in 47 patients with B cell non-Hodgkin's lymphoma (n\u00a0=\u00a017), multiple myeloma (n\u00a0=\u00a013), or CD (n\u00a0=\u00a017).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25784388", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1754, "text": "Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "endSection": "abstract" }, { "offsetInBeginSection": 1916, "offsetInEndSection": 2260, "text": "Three (6%) of 53 patients had serious adverse events judged reasonably related to siltuximab (lower respiratory tract infection, anaphylactic reaction, sepsis).Siltuximab plus best supportive care was superior to best supportive care alone for patients with symptomatic multicentric Castlemans disease and well tolerated with prolonged exposure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25042199", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 557, "text": "Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD.This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26327301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26124203", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26124203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Siltuximab for multicentric Castleman disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25110138", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601959", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25042199", "endSection": "title" }, { "offsetInBeginSection": 217, "offsetInEndSection": 447, "text": "EXPERIMENTAL DESIGN: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659971", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1756, "text": "Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 415, "text": "To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601959", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 767, "text": "Clinical benefit response (CBR; composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest lymph node size) was also evaluated in Castleman disease.Sixty-seven patients received a median of 16 siltuximab doses for a median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659971", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 517, "text": "The recent approvals in North America, Europe and Brazil of siltuximab, a monoclonal antibody against IL-6, for iMCD now provide a safe and effective therapy that targets a key aspect of pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26634298", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 793, "text": "Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26869762", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1594, "text": "No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days).These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 492, "text": "Siltuximab is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD.METHODS: We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20625121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Siltuximab for multicentric Castleman disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25110138", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26634298", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Emerging treatments in Castleman disease - a critical appraisal of siltuximab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26869762", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Siltuximab (Sylvant). Castleman's disease: good symptomatic efficacy in some patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27152394", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Siltuximab: a new option for the management of Castleman's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685858", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25042199", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26394632", "endSection": "title" } ] }, { "body": "What are Degrons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7731961", "http://www.ncbi.nlm.nih.gov/pubmed/23960079", "http://www.ncbi.nlm.nih.gov/pubmed/10545113", "http://www.ncbi.nlm.nih.gov/pubmed/26743630", "http://www.ncbi.nlm.nih.gov/pubmed/20924402", "http://www.ncbi.nlm.nih.gov/pubmed/23271452", "http://www.ncbi.nlm.nih.gov/pubmed/16606826", "http://www.ncbi.nlm.nih.gov/pubmed/22577142", "http://www.ncbi.nlm.nih.gov/pubmed/21190544", "http://www.ncbi.nlm.nih.gov/pubmed/26732515", "http://www.ncbi.nlm.nih.gov/pubmed/25157437", "http://www.ncbi.nlm.nih.gov/pubmed/23431188", "http://www.ncbi.nlm.nih.gov/pubmed/26435348", "http://www.ncbi.nlm.nih.gov/pubmed/18698327", "http://www.ncbi.nlm.nih.gov/pubmed/19878048", "http://www.ncbi.nlm.nih.gov/pubmed/21633985", "http://www.ncbi.nlm.nih.gov/pubmed/26456660", "http://www.ncbi.nlm.nih.gov/pubmed/20835240" ], "ideal_answer": [ "Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system.", "Portable degradation sequences, or degrons, have the ability to bind to E3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters.", "portable degradation sequences, or degrons, have the ability to bind to e3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters." ], "type": "summary", "id": "58cdbaf302b8c60953000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26732515", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 911, "text": "Portable degradation sequences, or degrons, have the ability to bind to E3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26456660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The N-degrons, a set of degradation signals recognized by the N-end rule pathway, comprise a protein's destabilizing N-terminal residue and an internal lysine residue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The ubiquitin-proteasome system degrades an enormous variety of proteins that contain specific degradation signals, or 'degrons'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18698327", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 375, "text": "Degron refers to an amino acid sequence that encodes a protein degradation signal, which is oftentimes a poly-ubiquitin chain that can be transferred to other proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26435348", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 311, "text": "Degradation signals (degrons) that are targeted by the N-end rule pathway include a set called N-degrons. The main determinant of an N-degron is a destabilizing N-terminal residue of a protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21633985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The N-end rule pathway is a proteolytic system in which destabilizing N-terminal amino acids of short lived proteins are recognized by recognition components (N-recognins) as an essential element of degrons, called N-degrons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22577142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20835240", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 940, "text": "More than 25 years ago, the first degradation signal was discovered and defined as destabilizing N-terminal amino-acid residue (or N-degron) of protein substrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26743630", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 716, "text": "A protein domain called \"degron\", which induces rapid proteolysis by the proteasome, can be used for this purpose. Degron-based technologies for the conditional depletion of POI--degron fusion proteins have been developed by exploiting various pathways leading to proteasomal degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23271452", "endSection": "abstract" } ] }, { "body": "Which disease is associated with mutated Sox2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26130484", "http://www.ncbi.nlm.nih.gov/pubmed/26893459", "http://www.ncbi.nlm.nih.gov/pubmed/25542770", "http://www.ncbi.nlm.nih.gov/pubmed/26250054" ], "ideal_answer": [ "SOX2 anophthalmia syndrome is an uncommon autosomal dominant syndrome caused by mutations in the SOX2 gene and clinically characterized by severe eye malformations (anophthalmia/microphthalmia) and extraocular anomalies mainly involving brain, esophagus, and genitalia." ], "exact_answer": [ "SOX2 anophthalmia syndrome" ], "type": "factoid", "id": "58ce9bf1d46b5c2951000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26130484", "endSection": "abstract" }, { "offsetInBeginSection": 45, "offsetInEndSection": 296, "text": "anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are the most frequent contributors to severe ODA, yet account for a minority of the genetic drivers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26893459", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 548, "text": "Three causative SOX2 mutations were found in subjects with syndromic A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25542770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "SOX2 anophthalmia syndrome is an uncommon autosomal dominant syndrome caused by mutations in the SOX2 gene and clinically characterized by severe eye malformations (anophthalmia/microphthalmia) and extraocular anomalies mainly involving brain, esophagus, and genitalia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26250054", "endSection": "abstract" } ] }, { "body": "Is the enzyme EPRS phosphorylated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27729295", "http://www.ncbi.nlm.nih.gov/pubmed/21220307", "http://www.ncbi.nlm.nih.gov/pubmed/19647514", "http://www.ncbi.nlm.nih.gov/pubmed/23071094" ], "ideal_answer": [ "Yes, EPRS is dually phosphorylated by cyclin-dependent kinase 5 (Cdk5) at Ser(886) and then by a Cdk5-dependent-AGC kinase at Ser(999)" ], "exact_answer": "yes", "type": "yesno", "id": "58cd522902b8c60953000038", "snippets": [ { "offsetInBeginSection": 368, "offsetInEndSection": 560, "text": "Phosphorylation of glutamyl-prolyl tRNA synthetase (EPRS) has been investigated extensively in our laboratory for more than a decade, and has served as an archetype for studies of other AARSs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729295", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 579, "text": "EPRS is dually phosphorylated by cyclin-dependent kinase 5 (Cdk5) at Ser(886) and then by a Cdk5-dependent-AGC kinase at Ser(999); ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071094", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 997, "text": "Diphosphorylated EPRS is released from its residence in the tRNA multisynthetase complex for immediate binding to NS1-associated protein and subsequent binding to ribosomal protein L13a and GAPDH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21220307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19647514", "endSection": "title" } ] }, { "body": "Which disease the skin condition Necrobiosis lipoidica diabeticorum is associated to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11259927", "http://www.ncbi.nlm.nih.gov/pubmed/24575162", "http://www.ncbi.nlm.nih.gov/pubmed/17429587", "http://www.ncbi.nlm.nih.gov/pubmed/730866", "http://www.ncbi.nlm.nih.gov/pubmed/8261754", "http://www.ncbi.nlm.nih.gov/pubmed/16060710", "http://www.ncbi.nlm.nih.gov/pubmed/18357585", "http://www.ncbi.nlm.nih.gov/pubmed/7851128", "http://www.ncbi.nlm.nih.gov/pubmed/12183729", "http://www.ncbi.nlm.nih.gov/pubmed/18377597", "http://www.ncbi.nlm.nih.gov/pubmed/8733162", "http://www.ncbi.nlm.nih.gov/pubmed/20537071", "http://www.ncbi.nlm.nih.gov/pubmed/7501550", "http://www.ncbi.nlm.nih.gov/pubmed/18092383", "http://www.ncbi.nlm.nih.gov/pubmed/23762652", "http://www.ncbi.nlm.nih.gov/pubmed/3351015", "http://www.ncbi.nlm.nih.gov/pubmed/19715570", "http://www.ncbi.nlm.nih.gov/pubmed/24283101", "http://www.ncbi.nlm.nih.gov/pubmed/27016885", "http://www.ncbi.nlm.nih.gov/pubmed/25266162", "http://www.ncbi.nlm.nih.gov/pubmed/23969033", "http://www.ncbi.nlm.nih.gov/pubmed/2102235", "http://www.ncbi.nlm.nih.gov/pubmed/20524475", "http://www.ncbi.nlm.nih.gov/pubmed/19380665", "http://www.ncbi.nlm.nih.gov/pubmed/18718195", "http://www.ncbi.nlm.nih.gov/pubmed/12180894", "http://www.ncbi.nlm.nih.gov/pubmed/23595890", "http://www.ncbi.nlm.nih.gov/pubmed/26975548" ], "ideal_answer": [ "Necrobiosis lipoidica diabeticorum (NLD) is a rare, granulomatous inflammatory skin disease of unknown origin, sometimes associated with diabetes mellitus." ], "exact_answer": [ "Diabetes mellitus" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009335", "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.disease-ontology.org/api/metadata/DOID:3486" ], "type": "factoid", "id": "58bfd8e902b8c60953000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Necrobiosis lipoidica diabeticorum (NLD) is a chronic condition, which is characterized by single or multiple lesions on the legs, and occurs in 0.3% of patients with diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25266162", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 221, "text": "Necrobiosis lipoidica (NL) is a rare chronic granulomatous dermatitis that usually appears in the lower extremities. It affects about 0.3-1.2% of diabetic patients, the majority of whom have type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24575162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "A 32-year-old woman with type 2 diabetes mellitus suffering from morbid obesity with BMI 45,14\u2009kg/m(2) was operated on. Not only the type 2DM but also one of its complication known as necrobiosis lipoidica diabeticorum remitted postoperatively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23762652", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 616, "text": "Necrobiosis lipoidica is a granulomatous skin disease of unknown etiology, associated mainly with diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23762652", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 133, "text": "Necrobiosis lipoidica diabeticorum is a rare disease of unclear etiology, that occurs in about 1% of diabetic patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715570", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 168, "text": "Necrobiosis lipoidica diabeticorum (NLD) is a rare, granulomatous inflammatory skin disease of unknown origin, sometimes associated with diabetes mellitus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Necrobiosis lipoidica diabeticorum (NLD) is a rare skin condition associated with diabetes, which characteristically occurs in the pretibial region of the lower limbs (Boulton et al., 1988).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11259927", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 302, "text": "More than half of the patients with necrobiosis lipoidica diabeticorum have diabetes mellitus, but less than one per cent of diabetes mellitus patients have necrobiosis lipoidica diabeticorum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8733162", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 390, "text": "We describe the unusual case of a woman with diabetes and a history of generalized granuloma annulare who noted leg ulcers that clinically represented ulcerated necrobiosis lipoidica diabeticorum and had histologic features of necrobiosis lipoidica diabeticorum and granuloma annulare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7851128", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Necrobiosis lipoidica diabeticorum (NLD) is a rare, granulomatous inflammatory skin disease of unknown origin, sometimes associated with diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Necrobiosis lipoidica diabeticorum (NLD) is a rare skin condition associated with diabetes, which characteristically occurs in the pretibial region of the lower limbs (Boulton et al., 1988)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11259927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Necrobiosis lipoidica is a rare inflammatory granulomatous skin disease of unknown etiology which is associated with diabetes mellitus in about 60\u2009% of the patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23595890", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 615, "text": "Necrobiosis lipoidica is a granulomatous skin disease of unknown etiology, associated mainly with diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23762652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Necrobiosis lipoidica is an inflammatory granulomatous skin disease of unknown etiology which is associated with diabetes mellitus in about 60% of the patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17429587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Necrobiosis lipoidica dibeticum (NLD) is a granulomatous skin disease mostly associated with diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18092383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Necrobiosis lipoidica (NL) is a rare chronic granulomatous disease that has historically been associated with diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23969033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Necrobiosis lipoidica diabeticorum is an unusual dermatologic condition with a characteristic clinical appearance and a clear association with diabetes mellitus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3351015", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 447, "text": "However, it has not been associated previously with necrobiosis lipoidica diabeticorum (NBL), a rare skin manifestation of diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2102235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Necrobiosis lipoidica diabeticorum (NLD) is a rare, granulomatous inflammatory skin disease of unknown origin, sometimes associated with diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Necrobiosis lipoidica diabeticorum (NLD) is a rare degenerative connective tissue disorder associated with diabetes mellitus, which usually presents with red papules or plaques with raised edges and occasional ulceration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26975548", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 401, "text": "We describe two children with diabetes who both developed granuloma annulare and later, necrobiosis lipoidica diabeticorum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20537071", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 277, "text": "Granuloma annulare occurs earlier than necrobiosis lipoidica diabeticorum and the association with diabetes mellitus is much weaker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20537071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Diabetes mellitus is associated with a range of dermatologic presentations, including granuloma annulare and necrobiosis lipoidica diabeticorum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20537071", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 273, "text": "In this report a patient with diabetes mellitus and generalized necrobiosis lipoidica diabeticorum with localization in surgical scars is described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/730866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Necrobiosis lipoidica is an idiopathic dermatological condition that is strongly associated with diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18718195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Necrobiosis lipoidica diabeticorum is an unusual dermatologic condition with a characteristic clinical appearance and a clear association with diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3351015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Necrobiosis lipoidica diabeticorum is a rare skin disorder, usually considered a marker for diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8733162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Recurrent necrobiosis lipoidica diabeticorum associated with venous insufficiency in an adolescent with poorly controlled type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12183729", "endSection": "title" } ] }, { "body": "What is the role of Lysine 2-hydroxyisobutyrylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24681537" ], "ideal_answer": [ "Lysine 2-hydroxyisobutyrylation (Khib) is a widely distributed active histone mark. This histone mark was initially identified by MS and then validated by chemical and biochemical methods. Histone Khib shows distinct genomic distributions from histone Kac or histone Kcr during male germ cell differentiation. In male germ cells, H4K8hib is associated with active gene transcription in meiotic and post-meiotic cells. In addition, H4K8ac-associated genes are included in and constitute only a subfraction of H4K8hib-labeled genes. The histone Khib mark is conserved and widely distributed, has high stoichiometry and induces a large structural change." ], "concepts": [ "http://www.biosemantics.org/jochem#4005689", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275269", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008239", "http://www.biosemantics.org/jochem#4278518", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4005689", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421", "http://www.biosemantics.org/jochem#4275268", "http://www.biosemantics.org/jochem#4275269" ], "type": "summary", "id": "589474467d9090f353000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1048, "text": "We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse histone Khib sites, including 27 unique lysine sites that are not known to be modified by lysine acetylation (Kac) and lysine crotonylation (Kcr). This histone mark was initially identified by MS and then validated by chemical and biochemical methods. Histone Khib shows distinct genomic distributions from histone Kac or histone Kcr during male germ cell differentiation. Using chromatin immunoprecipitation sequencing, gene expression analysis and immunodetection, we show that in male germ cells, H4K8hib is associated with active gene transcription in meiotic and post-meiotic cells. In addition, H4K8ac-associated genes are included in and constitute only a subfraction of H4K8hib-labeled genes. The histone Khib mark is conserved and widely distributed, has high stoichiometry and induces a large structural change. These findings suggest its critical role on the regulation of chromatin functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse histone Khib sites, including 27 unique lysine sites that are not known to be modified by lysine acetylation (Kac) and lysine crotonylation (Kcr).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse histone Khib sites, including 27 unique lysine sites that are not known to be modified by lysine acetylation (Kac) and lysine crotonylation (Kcr)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse histone Khib sites, including 27 unique lysine sites that are not known to be modified by lysine acetylation (Kac) and lysine crotonylation (Kcr). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 965, "text": "The histone Khib mark is conserved and widely distributed, has high stoichiometry and induces a large structural change.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681537", "endSection": "title" } ] }, { "body": "List diseases associated with the Dopamine Receptor D4 (DRD4).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22610946", "http://www.ncbi.nlm.nih.gov/pubmed/25659462", "http://www.ncbi.nlm.nih.gov/pubmed/25983551" ], "ideal_answer": [ "The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD)." ], "exact_answer": [ [ "attention deficit hyperactivity disorder", "ADHD" ], [ "susceptibility to neuropsychiatric diseases" ] ], "type": "list", "id": "58cd59cb02b8c60953000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25659462", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 296, "text": "The variable number of tandem repeats (VNTR) of the dopamine receptor D4 (DRD4) gene among humans may elucidate individual differences in susceptibility to neuropsychiatric diseases. Dopamine dysfunction may be involved with Attention Deficit Hyperactivity Disorder (ADHD) symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25983551", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 720, "text": "This review summarized the ongoing research of DA receptor genes in ADHD pathogenesis and gathered the past published data with meta-analysis and revealed the high risk of DRD5, DRD2, and DRD4 polymorphisms in ADHD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22610946", "endSection": "abstract" } ] }, { "body": "Which bacteria cause diphtheria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8784575", "http://www.ncbi.nlm.nih.gov/pubmed/24403054", "http://www.ncbi.nlm.nih.gov/pubmed/7766139", "http://www.ncbi.nlm.nih.gov/pubmed/23981100", "http://www.ncbi.nlm.nih.gov/pubmed/14532240", "http://www.ncbi.nlm.nih.gov/pubmed/23357389", "http://www.ncbi.nlm.nih.gov/pubmed/812306", "http://www.ncbi.nlm.nih.gov/pubmed/22205447", "http://www.ncbi.nlm.nih.gov/pubmed/21087580", "http://www.ncbi.nlm.nih.gov/pubmed/25578079", "http://www.ncbi.nlm.nih.gov/pubmed/21549738", "http://www.ncbi.nlm.nih.gov/pubmed/1901182", "http://www.ncbi.nlm.nih.gov/pubmed/25887321", "http://www.ncbi.nlm.nih.gov/pubmed/23163039", "http://www.ncbi.nlm.nih.gov/pubmed/21742447", "http://www.ncbi.nlm.nih.gov/pubmed/26607400", "http://www.ncbi.nlm.nih.gov/pubmed/22403045", "http://www.ncbi.nlm.nih.gov/pubmed/22583953", "http://www.ncbi.nlm.nih.gov/pubmed/25320226", "http://www.ncbi.nlm.nih.gov/pubmed/16107839", "http://www.ncbi.nlm.nih.gov/pubmed/24295558", "http://www.ncbi.nlm.nih.gov/pubmed/12661461", "http://www.ncbi.nlm.nih.gov/pubmed/10220818", "http://www.ncbi.nlm.nih.gov/pubmed/12037265", "http://www.ncbi.nlm.nih.gov/pubmed/25297035", "http://www.ncbi.nlm.nih.gov/pubmed/22568715", "http://www.ncbi.nlm.nih.gov/pubmed/10598381", "http://www.ncbi.nlm.nih.gov/pubmed/16406634", "http://www.ncbi.nlm.nih.gov/pubmed/24293345", "http://www.ncbi.nlm.nih.gov/pubmed/22628666", "http://www.ncbi.nlm.nih.gov/pubmed/25587356", "http://www.ncbi.nlm.nih.gov/pubmed/18583986", "http://www.ncbi.nlm.nih.gov/pubmed/24106714", "http://www.ncbi.nlm.nih.gov/pubmed/3112181", "http://www.ncbi.nlm.nih.gov/pubmed/10932611", "http://www.ncbi.nlm.nih.gov/pubmed/24572455", "http://www.ncbi.nlm.nih.gov/pubmed/11568853", "http://www.ncbi.nlm.nih.gov/pubmed/22382258" ], "ideal_answer": [ "Diphtheria is caused by the bacteria:\n1) Corynebacterium ulcerans and \n2) Corynebacterium diphtheriae." ], "exact_answer": [ [ "Corynebacterium ulcerans", "C. ulcerans" ], [ "Corynebacterium diphtheriae", "C. diphtheriae" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001419", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003354", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003352", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004167", "http://www.disease-ontology.org/api/metadata/DOID:11405", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004165" ], "type": "list", "id": "58b548d722d3005309000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Corynebacterium ulcerans is a zoonotic pathogen that can produce diphtheria toxin and causes an illness categorized as diphtheria in the European Union because its clinical appearance is similar to that of diphtheria caused by Corynebacterium diphtheriae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26607400", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 444, "text": "The zoonotic bacterium Corynebacterium ulcerans may be pathogenic both in humans and animals: toxigenic strains can cause diphtheria or diphtheria-like disease in humans via diphtheria toxin, while strains producing the dermonecrotic exotoxin phospholipase D may lead to caseous lymphadenitis primarily in wild animals. Diphtheria toxin-positive Corynebacterium ulcerans strains have been isolated mainly from cattle, dogs and cats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887321", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 619, "text": "Corynebacterium diphtheriae, a pathogenic bacterium that causes diphtheria, has been performed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Corynebacterium ulcerans 0102 carries the gene encoding diphtheria toxin on a prophage different from the C. diphtheriae NCTC 13129 prophage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22583953", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 299, "text": "Corynebacterium ulcerans can cause a diphtheria-like illness, especially when the bacterium is lysogenized with a tox gene-carrying bacteriophage that produces diphtheria toxin. Acquisition of toxigenicity upon phage lysogenization is a common feature of C. ulcerans and C. diphtheriae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22583953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Corynebacterium ulcerans (toxigenic C. ulcerans) produces the diphtheria toxin, which causes pharyngeal and cutaneous diphtheria-like disease in people, and this bacterium is commonly detected in dogs and cats that are reared at home. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25578079", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 454, "text": "This case demonstrates that strains of C. ulcerans that produce diphtheria toxin can cause infections of the skin that completely mimic typical cutaneous diphtheria, thereby potentially providing a source of bacteria capable of causing life-threatening diseases in the patient's environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11568853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Diphtheria is a serious upper respiratory tract disease caused by the diphtheria toxin (DT) secreted from the bacteria Corynebacterium diphtheriae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22205447", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 213, "text": "ulcerans produce diphtheria toxin, which can cause life-threatening cardiopathies and neuropathies in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "A high-density growth approach was utilized to produce mutated diphtheria toxin from two strains of Corynebacterium diphtheria: C7 (beta)(tox-201,tox-9) and C7 (beta)(tox-107).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7766139", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1190, "text": "For the primary prevention of disease caused by diphtheria toxin-producing corynebacteria, vaccination with diphtheria toxoid is recommended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403045", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 455, "text": "ulcerans that produce diphtheria toxin can cause infections of the skin that completely mimic typical cutaneous diphtheria, thereby potentially providing a source of bacteria capable of causing life-threatening diseases in the patient's environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11568853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "[A case of diphtheria in the Netherlands due to an infection with Corynebacterium ulcerans].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12661461", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Diphtheria is an acute bacterial illness caused by toxigenic strains of Corynebacterium diphtheriae (C. diphtheriae)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22382258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Diphtheria is caused by diphtheria toxin-producing Corynebacterium species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22628666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Diphtheria, an acute infectious condition caused by Corynebacterium diphtheriae, was once a major killer of children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Diphtheria, caused by toxigenic strains of Corynebacterium diphtheriae, is an ancient disease with high incidence and mortality that has always been characterized by epidemic waves of occurrence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22568715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Infections caused by Corynebacterium diphtheriae frequently induce situations in which very small doses of antigens injected intradermally can cause strong inflammatory reactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Corynebacterium diphtheriae is the etiological agent of diphtheria, a potential fatal disease caused by a corynephage toxin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "[Diphtheria in Denmark 1956-1989. Occurrence of Corynebacterium diphtheriae and other diphtheria toxigenic bacteria].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1901182", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry as a tool for rapid diagnosis of potentially toxigenic Corynebacterium species in the laboratory management of diphtheria-associated bacteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21087580", "endSection": "title" }, { "offsetInBeginSection": 164, "offsetInEndSection": 456, "text": "This case demonstrates that strains of C. ulcerans that produce diphtheria toxin can cause infections of the skin that completely mimic typical cutaneous diphtheria, thereby potentially providing a source of bacteria capable of causing life-threatening diseases in the patient's environment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11568853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Detection of differences in the nucleotide and amino acid sequences of diphtheria toxin from Corynebacterium diphtheriae and Corynebacterium ulcerans causing extrapharyngeal infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14532240", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Heterogeneity of diphtheria toxin gene, tox, and its regulatory element, dtxR, in Corynebacterium diphtheriae strains causing epidemic diphtheria in Russia and Ukraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8784575", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Diphtheria is a serious upper respiratory tract disease caused by the diphtheria toxin (DT) secreted from the bacteria Corynebacterium diphtheriae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22205447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Laboratory guidelines for the diagnosis of infections caused by Corynebacterium diphtheriae and C. ulcerans. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10598381", "endSection": "title" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1374, "text": "A possible biological mechanism for a diphtheria effect on hearing ability exists: The toxin produced by the Corynebacterium diphtheriae bacteria can cause damage to cranial nerves and therefore may affect the auditory neural pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12037265", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1328, "text": "A possible biological mechanism for a diphtheria effect on hearing ability exists: The toxin produced by the Corynebacterium diphtheriae bacteria can cause damage to cranial nerves and therefore may affect the auditory neural pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12037265", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 848, "text": "In cases of human infection with potentially toxigenic corynebacteria, it is important to determine the species and examine the isolate for diphtheria toxin production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 916, "text": "AIM: Study of the apoptogenic effect of Corynebacterium diphtheriae toxigenic strains on mice peritoneal macrophages in vitro.MATERIALS AND METHODS: Evaluation ofapoptosis induced by Corynebacterium diphtheriae, Corynebacterium pseudodiphtheriticum, Staphylococcus aureus, Streptococcus pyogenes strains was performed by characteristic morphological changes in macrophages in smears stained by azure eosin by Romanovsky-Giemsa.RESULTS: Apoptogenic activity of diphtheria infectious agent was established to be determined by diphtheria exotoxin at early (after 1 hour) and surface structures and pathogenicity enzymes at later (3 hours) stages of effect.CONCLUSION: The ability of diphtheria infectious agent to cause macrophage apoptosis is one of the mechanisms of realization of its pathogenic properties determined by the effect of diphtheria exotoxin, as well as its surface structures and pathogenicity enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23163039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Extrapharyngeal infections caused by Corynebacterium ulcerans have rarely been reported previously, and diphtheria toxin production has usually not been addressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11568853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Corynebacterium ulcerans may cause diphtheria in humans and caseous lymphadenitis in animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24572455", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 979, "text": "ulcerans for the first time, we show that related sequence types (STs) might be associated with the presence of the diphtheria toxin gene, which encodes diphtheria toxin (DT), the most important diphtheria-causing virulence factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25320226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Human-to-human-transmitted Corynebacterium diphtheriae was historically the main pathogen causing diphtheria and has therefore been studied extensively in the past.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25320226", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 851, "text": "Toxigenic Corynebacterium diphtheriae, the organism causing diphtheria, was thought to have become rare or even have disappeared from previously endemic areas such as South Dakota.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10932611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Infection of the skin caused by Corynebacterium ulcerans and mimicking classical cutaneous diphtheria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11568853", "endSection": "title" } ] }, { "body": "What is the function of calcium-sensing receptor (CaSR)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23856267", "http://www.ncbi.nlm.nih.gov/pubmed/21566074", "http://www.ncbi.nlm.nih.gov/pubmed/26608608", "http://www.ncbi.nlm.nih.gov/pubmed/26386835", "http://www.ncbi.nlm.nih.gov/pubmed/26261299" ], "ideal_answer": [ "The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays an essential role in maintaining calcium homeostasis.\nThe CaSR is a key regulator for such diverse processes as hormone secretion, gene expression, inflammation, proliferation, differentiation, and apoptosis. Due to this pleiotropy, the CaSR is able to regulate cell fate and is implicated in the development of many types of benign or malignant tumours of the breast, prostate, parathyroid, and colon." ], "exact_answer": [ "The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays an essential role in maintaining calcium homeostasis." ], "type": "factoid", "id": "58cd7fed02b8c6095300003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays an essential role in maintaining calcium homeostasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26386835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The CaSR is ubiquitously expressed, implying a wide range of functions regulated by this receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26608608", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 1037, "text": "The CaSR is a key regulator for such diverse processes as hormone secretion, gene expression, inflammation, proliferation, differentiation, and apoptosis. Due to this pleiotropy, the CaSR is able to regulate cell fate and is implicated in the development of many types of benign or malignant tumours of the breast, prostate, parathyroid, and colon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26608608", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 326, "text": "Extracellular calcium-sensing receptor (CaSR) and ovarian cancer gene receptor 1 (OGR1) are two GPCRs that sense extracellular Ca(2+) and H(+), respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261299", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 179, "text": " The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21566074", "endSection": "abstract" } ] }, { "body": "List drug that were evaluated in the CHAMP trial for migraine.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "http://www.ncbi.nlm.nih.gov/pubmed/27039826", "http://www.ncbi.nlm.nih.gov/pubmed/27788026" ], "ideal_answer": [ "Childhood and Adolescent Migraine Prevention (CHAMP) trial evaluated effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents." ], "exact_answer": [ [ "amitriptyline" ], [ "topiramate" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:6364", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430" ], "type": "list", "id": "589a245a78275d0c4a000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "OBJECTIVE: To describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27039826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Childhood and Adolescent Migraine Prevention (CHAMP) study: a double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo in the prevention of childhood and adolescent migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "title" }, { "offsetInBeginSection": 651, "offsetInEndSection": 998, "text": "METHODS: CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1524, "text": "The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8-week period to a target dose of 1\u2009mg/kg of amitriptyline and 2\u2009mg/kg of topiramate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "abstract" }, { "offsetInBeginSection": 1667, "offsetInEndSection": 1850, "text": "CONCLUSIONS: The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "To describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27039826", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 997, "text": "The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents.METHODS: CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Childhood and Adolescent Migraine Prevention (CHAMP) study: a double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo in the prevention of childhood and adolescent migraine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "title" }, { "offsetInBeginSection": 478, "offsetInEndSection": 975, "text": "The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents.CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "abstract" }, { "offsetInBeginSection": 1669, "offsetInEndSection": 1853, "text": "CONCLUSIONS: The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Childhood and Adolescent Migraine Prevention (CHAMP) study: a double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo in the prevention of childhood and adolescent migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594025", "endSection": "title" } ] }, { "body": "What is the role of IL-18BP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26782741", "http://www.ncbi.nlm.nih.gov/pubmed/26898120", "http://www.ncbi.nlm.nih.gov/pubmed/27914933", "http://www.ncbi.nlm.nih.gov/pubmed/26850179", "http://www.ncbi.nlm.nih.gov/pubmed/25692120", "http://www.ncbi.nlm.nih.gov/pubmed/25807634", "http://www.ncbi.nlm.nih.gov/pubmed/25182570", "http://www.ncbi.nlm.nih.gov/pubmed/25548255" ], "ideal_answer": [ "IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting." ], "exact_answer": [ "IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting." ], "type": "factoid", "id": "58cd90c202b8c60953000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Interleukin 18--binding protein ameliorates liver ischemia--reperfusion injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26850179", "endSection": "title" }, { "offsetInBeginSection": 1549, "offsetInEndSection": 1719, "text": " IL-18BP exhibited anti-inflammatory, antioxidant, and protective effects in I/R-mediated hepatic injury via regulating some liver enzyme activities and cytokine levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26850179", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 1012, "text": "Because of IL-18's potential pro-inflammatory and tissue destructive effects, its biological activities are tightly controlled in the body by its naturally occurring antagonist called IL-18BP. The antagonist is produced in the body both constitutively and in response to an increased production of IL-18 as a negative feedback mechanism. Under physiological conditions, most of IL-18 in the circulation is bound with IL-18BP and is inactive. However, an imbalance in the production of IL-18 and its antagonist (an increase in the production of IL-18 with a decrease, no increase or an insufficient increase in the production of IL-18BP) has been described in many chronic inflammatory diseases in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26898120", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 441, "text": "L-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182570", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 761, "text": "Platelets also contain the IL-18 antagonist, the IL-18-Binding Protein (IL-18BP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914933", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 762, "text": "The natural inhibitor IL-18BP , whose production is enhanced by IFN-\u03b3 and IL-27, further regulates IL-18 activity in the extracellular environment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25548255", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 224, "text": "IL-18 binding protein (IL-18BP) is a naturally occurring inhibitor of IL-18. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25807634", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 374, "text": "IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25692120", "endSection": "abstract" } ] }, { "body": "Which protein mediates gene loop formation in the yeast S. cerevisiae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24124207", "http://www.ncbi.nlm.nih.gov/pubmed/22081613", "http://www.ncbi.nlm.nih.gov/pubmed/17803944", "http://www.ncbi.nlm.nih.gov/pubmed/21835917", "http://www.ncbi.nlm.nih.gov/pubmed/19602510", "http://www.ncbi.nlm.nih.gov/pubmed/18550805" ], "ideal_answer": [ "Moreover, looping is dependent upon the general transcription factor TFIIB: the E62K (glutamic acid 62 --> lysine) form of TFIIB adversely affects looping at every gene tested, including BLM10, SAC3, GAL10, SEN1, and HEM3. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP.", "Gene-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of genes, such as TFIIB. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP", "Gene looping, defined as the interaction of the promoter and the terminator regions of a gene during transcription, requires transcription factor IIB (TFIIB).", "A transcription-independent role for TFIIB in gene looping." ], "exact_answer": [ "TFIIB" ], "type": "factoid", "id": "58adc1ff9ef3c34033000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "A transcription-independent role for TFIIB in gene looping.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17803944", "endSection": "title" }, { "offsetInBeginSection": 290, "offsetInEndSection": 510, "text": "Moreover, looping is dependent upon the general transcription factor TFIIB: the E62K (glutamic acid 62 -->lysine) form of TFIIB adversely affects looping at every gene tested, including BLM10, SAC3, GAL10, SEN1, and HEM3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17803944", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 798, "text": "TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17803944", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1066, "text": "We present a high-resolution genome-wide map of TFIIB locations that implicates 3' NFRs in gene looping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18550805", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1107, "text": "Instead, activators physically interacted with the general transcription factor TFIIB when the genes were activated and in a looped configuration. TFIIB cross-linked to both the promoter and the terminator regions during the transcriptionally activated state of a gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19602510", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1428, "text": " We propose that the activators facilitate gene looping through their interaction with TFIIB during transcriptional activation of genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19602510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Gene looping, defined as the interaction of the promoter and the terminator regions of a gene during transcription, requires transcription factor IIB (TFIIB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835917", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 272, "text": "We have earlier demonstrated association of TFIIB with the distal ends of a gene in an activator-dependent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835917", "endSection": "abstract" }, { "offsetInBeginSection": 1578, "offsetInEndSection": 1698, "text": "Furthermore, TFIIB interaction with the CF1 complex and Pap1 is crucial for gene looping and transcriptional regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835917", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 226, "text": "TFIIB also cross-links to terminator regions and is required for gene loops that juxtapose promoter-terminator elements in a transcription-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081613", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1252, "text": "These results define a novel, functional interaction between TFIIB and Ssl2 that affects start site selection and gene looping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22081613", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 361, "text": "Gene-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of genes, such as TFIIB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24124207", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 359, "text": "Gene-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of genes, such as TFIIB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24124207", "endSection": "abstract" } ] }, { "body": "Which two drugs were compared in the ARISTOTLE Trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25173541", "http://www.ncbi.nlm.nih.gov/pubmed/26424386", "http://www.ncbi.nlm.nih.gov/pubmed/25294786", "http://www.ncbi.nlm.nih.gov/pubmed/24657685", "http://www.ncbi.nlm.nih.gov/pubmed/27463942", "http://www.ncbi.nlm.nih.gov/pubmed/22298161", "http://www.ncbi.nlm.nih.gov/pubmed/25498373", "http://www.ncbi.nlm.nih.gov/pubmed/24281250", "http://www.ncbi.nlm.nih.gov/pubmed/22449118", "http://www.ncbi.nlm.nih.gov/pubmed/22933567", "http://www.ncbi.nlm.nih.gov/pubmed/22572202", "http://www.ncbi.nlm.nih.gov/pubmed/26447668", "http://www.ncbi.nlm.nih.gov/pubmed/23036896", "http://www.ncbi.nlm.nih.gov/pubmed/21740079", "http://www.ncbi.nlm.nih.gov/pubmed/25332806", "http://www.ncbi.nlm.nih.gov/pubmed/26839066", "http://www.ncbi.nlm.nih.gov/pubmed/23619028", "http://www.ncbi.nlm.nih.gov/pubmed/23026665", "http://www.ncbi.nlm.nih.gov/pubmed/22056819", "http://www.ncbi.nlm.nih.gov/pubmed/24561548", "http://www.ncbi.nlm.nih.gov/pubmed/22787066", "http://www.ncbi.nlm.nih.gov/pubmed/23859143", "http://www.ncbi.nlm.nih.gov/pubmed/23883416", "http://www.ncbi.nlm.nih.gov/pubmed/25547937", "http://www.ncbi.nlm.nih.gov/pubmed/23796193", "http://www.ncbi.nlm.nih.gov/pubmed/22684583", "http://www.ncbi.nlm.nih.gov/pubmed/25854636", "http://www.ncbi.nlm.nih.gov/pubmed/22277459", "http://www.ncbi.nlm.nih.gov/pubmed/25497244", "http://www.ncbi.nlm.nih.gov/pubmed/27306620", "http://www.ncbi.nlm.nih.gov/pubmed/23869941" ], "ideal_answer": [ "Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial compared apixaban and warfarin." ], "exact_answer": [ [ "apixaban" ], [ "warfarin" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017428" ], "type": "list", "id": "589a246178275d0c4a00002b", "snippets": [ { "offsetInBeginSection": 262, "offsetInEndSection": 465, "text": "METHODS: We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26447668", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 469, "text": " In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.METHODS: The ARISTOTLE trial randomised 18,201 patients with AF to apixaban or warfarin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26839066", "endSection": "abstract" }, { "offsetInBeginSection": 1391, "offsetInEndSection": 1562, "text": "Moreover, apixaban was associated with decreased all-cause mortality (RR 0.89, 95% CI 0.81 to 0.99) although this finding was driven by the results of the ARISTOTLE trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547937", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 880, "text": "Compared with warfarin, apixaban (in the ARISTOTLE trial) and edoxaban (in the ENGAGE-AF trial) were shown to be superior or non-inferior, respectively, for reduction in stroke or SE risk in patients with AF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25854636", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 434, "text": "METHODS: A decision-analytic Markov model was constructed to assess the cost-effectiveness of apixaban versus warfarin, based on data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in AF (ARISTOTLE) trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24281250", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1406, "text": "The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22684583", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1410, "text": "The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22684583", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 880, "text": "We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons.We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 574, "text": "A comparative analysis of three major clinical trials with factor Xa inhibitor oral anticoagulant (XOAC) drugs versus warfarin in atrial fibrillation-Rocket-AF (rivaroxaban), Aristotle (apixaban) and Engage AF Timi 48 (edoxaban; two different doses and sets of data)-was carried out.Data were extracted from the original reports (study level) and a meta-analysis was carried out.When compared with warfarin, XOAC therapy was associated with a decrease in haemorrhagic stroke, with a similar pattern for all regimens and meta-analysis showing a risk ratio of 0.488 (95% CI 0.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572202", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25173541", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22933567", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 570, "text": "A comparative analysis of three major clinical trials with factor Xa inhibitor oral anticoagulant (XOAC) drugs versus warfarin in atrial fibrillation-Rocket-AF (rivaroxaban), Aristotle (apixaban) and Engage AF Timi 48 (edoxaban; two different doses and sets of data)-was carried out.Data were extracted from the original reports (study level) and a meta-analysis was carried out.When compared with warfarin, XOAC therapy was associated with a decrease in haemorrhagic stroke, with a similar pattern for all regimens and meta-analysis showing a risk ratio of 0.488 (95% C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 548, "text": "This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding.Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.All patients who received at least 1 dose of a study drug were included.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24657685", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 786, "text": "Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban.To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5 mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria.Among 18 201 patients in the ARISTOTLE trial, 17\u202f322 were included in this analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27463942", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 816, "text": "We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons.We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787066", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 640, "text": "This study aimed to evaluate the medical cost reductions associated with the use of individual NOACs instead of warfarin from the US payer perspective.Rates for efficacy and safety clinical events for warfarin were estimated as the weighted averages from the RE-LY, ROCKET-AF and ARISTOTLE trials, and event rates for NOACs were determined by applying trial hazard ratios or relative risk ratios to such weighted averages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22449118", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1169, "text": "The ARISTOTLE trial showed apixaban was superior to warfarin for stroke prevention, significantly reduced all major bleeding, and resulted in a significant reduction in all-cause mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859143", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1411, "text": "The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22684583", "endSection": "abstract" }, { "offsetInBeginSection": 1828, "offsetInEndSection": 2081, "text": "In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality, with a similar reduction in the rate of ischemic stroke and better tolerability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22684583", "endSection": "abstract" }, { "offsetInBeginSection": 1967, "offsetInEndSection": 2123, "text": "The results of the ARISTOTLE trial, which is evaluating apixaban against warfarin in \u223c18\u2009000 patients with AF, are expected to be available later this year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21740079", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1278, "text": "The Medco data did not contain information for patients receiving apixaban as it was not on the market at the time of analysis.RESULTS: Stroke and MB rates among RW NVAF patients during warfarin exposure were higher compared with event rates in patients treated with warfarin in ARISTOTLE (stroke: 5.29 vs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23796193", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 190, "text": "In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24561548", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 535, "text": "The ARISTOTLE trial compared apixaban with warfarin in 18 201 patients with AF and \u2265 1 additional risk factor for stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22056819", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 867, "text": "Compared with warfarin, apixaban (in the ARISTOTLE trial) and edoxaban (in the ENGAGE-AF trial) were shown to be superior or non-inferior, respectively, for reduction in stroke or SE risk in patients with AF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25854636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24561548", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572202", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22572202", "endSection": "abstract" } ] }, { "body": "What is REVIGO?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21789182" ], "ideal_answer": [ "REVIGO summarizes and visualizes long lists of gene ontology terms.", "REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures. Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views. REVIGO is freely available at http://revigo.irb.hr/.", "Outcomes of high-throughput biological experiments are typically interpreted by statistical testing for enriched gene functional categories defined by the Gene Ontology (GO). The resulting lists of GO terms may be large and highly redundant, and thus difficult to interpret.REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures. Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views. REVIGO is freely available at http://revigo.irb.hr/." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063990" ], "type": "summary", "id": "5891c754621ea6ff7e000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "REVIGO summarizes and visualizes long lists of gene ontology terms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "title" }, { "offsetInBeginSection": 274, "offsetInEndSection": 845, "text": "REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures. Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views. REVIGO is freely available at http://revigo.irb.hr/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 790, "text": "Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 479, "text": "The resulting lists of GO terms may be large and highly redundant, and thus difficult to interpret.REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "REVIGO summarizes and visualizes long lists of gene ontology terms", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "title" }, { "offsetInBeginSection": 175, "offsetInEndSection": 479, "text": "The resulting lists of GO terms may be large and highly redundant, and thus difficult to interpret.REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 791, "text": "Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 480, "text": "The resulting lists of GO terms may be large and highly redundant, and thus difficult to interpret.REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "REVIGO summarizes and visualizes long lists of gene ontology terms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "title" }, { "offsetInBeginSection": 481, "offsetInEndSection": 792, "text": "Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21789182", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of onartuzumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23922054", "http://www.ncbi.nlm.nih.gov/pubmed/22917884", "http://www.ncbi.nlm.nih.gov/pubmed/25806189", "http://www.ncbi.nlm.nih.gov/pubmed/27937096", "http://www.ncbi.nlm.nih.gov/pubmed/25074413", "http://www.ncbi.nlm.nih.gov/pubmed/27349303", "http://www.ncbi.nlm.nih.gov/pubmed/24101053", "http://www.ncbi.nlm.nih.gov/pubmed/27918764", "http://www.ncbi.nlm.nih.gov/pubmed/24687921", "http://www.ncbi.nlm.nih.gov/pubmed/26445503", "http://www.ncbi.nlm.nih.gov/pubmed/23894056", "http://www.ncbi.nlm.nih.gov/pubmed/25522765", "http://www.ncbi.nlm.nih.gov/pubmed/24493831", "http://www.ncbi.nlm.nih.gov/pubmed/25777467", "http://www.ncbi.nlm.nih.gov/pubmed/24258345", "http://www.ncbi.nlm.nih.gov/pubmed/24959087", "http://www.ncbi.nlm.nih.gov/pubmed/27856142", "http://www.ncbi.nlm.nih.gov/pubmed/23882082", "http://www.ncbi.nlm.nih.gov/pubmed/27401892", "http://www.ncbi.nlm.nih.gov/pubmed/27918718", "http://www.ncbi.nlm.nih.gov/pubmed/23063071", "http://www.ncbi.nlm.nih.gov/pubmed/23536720", "http://www.ncbi.nlm.nih.gov/pubmed/25818471", "http://www.ncbi.nlm.nih.gov/pubmed/23810377" ], "ideal_answer": [ "Onartuzumab is monoclonal antibody targeting MET. It works by inhibiting MET. Onartuzumab was tested for treatment of non-small cell lung carcinoma, adenocarcinoma of the stomach and gastroesophageal Junction, and recurrent glioblastoma." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ], "type": "summary", "id": "5890dcba621ea6ff7e000003", "snippets": [ { "offsetInBeginSection": 316, "offsetInEndSection": 503, "text": " In this study, e-training was used to train board-certified pathologists to evaluate non-small cell lung carcinoma for eligibility for treatment with onartuzumab, a MET-inhibiting agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27349303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "A Randomized Phase II Study of FOLFOX With or Without the MET Inhibitor Onartuzumab in Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27401892", "endSection": "title" }, { "offsetInBeginSection": 238, "offsetInEndSection": 331, "text": "MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27401892", "endSection": "abstract" }, { "offsetInBeginSection": 1721, "offsetInEndSection": 2173, "text": "CONCLUSION: The addition of onartuzumab to mFOLFOX6 in gastric cancer did not improve efficacy in an unselected population or in a MET immunohistochemistry-positive population.IMPLICATIONS FOR PRACTICE: The YO28252 study demonstrated that the addition of the anti-MET agent onartuzumab to mFOLFOX6 for treatment of gastric cancer did not improve efficacy in an overall study population or those selected for positive MET status by immunohistochemistry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27401892", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 433, "text": " The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27918718", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 376, "text": "We report results of METGastric, a phase 3 trial of the MET inhibitor onartuzumab plus standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27918764", "endSection": "abstract" }, { "offsetInBeginSection": 1678, "offsetInEndSection": 1872, "text": "Conclusion Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter OS in the onartuzumab arm, compared with erlotinib in patients with MET-positive non-small-cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27937096", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 657, "text": "A recent example of a failed trial is the Phase III MetLung trial that compared the effects of the c-MET monovalent antibody onartuzumab with erlotinib versus erlotinib alone in late-stage non-small-cell lung cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25818471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23882082", "endSection": "title" }, { "offsetInBeginSection": 336, "offsetInEndSection": 496, "text": "Because onartuzumab, a monovalent antibody to MET, blocks HGF-induced MET activation, the addition of onartuzumab to erlotinib may improve therapeutic efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25522765", "endSection": "abstract" }, { "offsetInBeginSection": 1118, "offsetInEndSection": 1330, "text": "Because binding of sMET to onartuzumab in circulation resulted in increasing sMET serum concentrations due to reduced clearance, this likely renders sMET unsuitable as a pharmacodynamic biomarker for onartuzumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24258345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Onartuzumab, a humanized, monovalent monoclonal anti-MET antibody, antagonizes MET signaling by inhibiting binding of its ligand, hepatocyte growth factor (HGF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24258345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23882082", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Nonclinical evaluation of the serum pharmacodynamic biomarkers HGF and shed MET following dosing with the anti-MET monovalent monoclonal antibody onartuzumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24258345", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Onartuzumab, a recombinant humanized monovalent monoclonal antibody directed against MET, the receptor for the hepatocyte growth factor, has been investigated for the treatment of solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26445503", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 943, "text": "Successful therapeutic targeting of the MET/HGF pathway has been achieved using monoclonal antibodies against the MET receptor and its ligand HGF in addition to MET-specific and multitargeted small-molecule tyrosine-kinase inhibitors with several drugs in late-phase clinical trials including onartuzumab, rilotumumab, tivantinib, and cabozantinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24959087", "endSection": "abstract" }, { "offsetInBeginSection": 1504, "offsetInEndSection": 2091, "text": "Grade 3-5 adverse events (AEs) were seen in 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively.The addition of onartuzumab to mFOLFOX6 in gastric cancer did not improve efficacy in an unselected population or in a MET immunohistochemistry-positive population.The YO28252 study demonstrated that the addition of the anti-MET agent onartuzumab to mFOLFOX6 for treatment of gastric cancer did not improve efficacy in an overall study population or those selected for positive MET status by immunohistochemistry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27401892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23882082", "endSection": "title" } ] }, { "body": "Is there a relationship between B cells and Multiple Sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25267439", "http://www.ncbi.nlm.nih.gov/pubmed/19996075", "http://www.ncbi.nlm.nih.gov/pubmed/26857494", "http://www.ncbi.nlm.nih.gov/pubmed/25666875", "http://www.ncbi.nlm.nih.gov/pubmed/26604134", "http://www.ncbi.nlm.nih.gov/pubmed/26732544", "http://www.ncbi.nlm.nih.gov/pubmed/18388800", "http://www.ncbi.nlm.nih.gov/pubmed/27120609", "http://www.ncbi.nlm.nih.gov/pubmed/24679343", "http://www.ncbi.nlm.nih.gov/pubmed/1839591", "http://www.ncbi.nlm.nih.gov/pubmed/25750917", "http://www.ncbi.nlm.nih.gov/pubmed/23634189", "http://www.ncbi.nlm.nih.gov/pubmed/18474519", "http://www.ncbi.nlm.nih.gov/pubmed/18388801", "http://www.ncbi.nlm.nih.gov/pubmed/20558389", "http://www.ncbi.nlm.nih.gov/pubmed/20970478", "http://www.ncbi.nlm.nih.gov/pubmed/24526661", "http://www.ncbi.nlm.nih.gov/pubmed/26724102", "http://www.ncbi.nlm.nih.gov/pubmed/18388796", "http://www.ncbi.nlm.nih.gov/pubmed/20535037", "http://www.ncbi.nlm.nih.gov/pubmed/26810546", "http://www.ncbi.nlm.nih.gov/pubmed/25620021", "http://www.ncbi.nlm.nih.gov/pubmed/25895531", "http://www.ncbi.nlm.nih.gov/pubmed/21216828", "http://www.ncbi.nlm.nih.gov/pubmed/15800022" ], "ideal_answer": [ "MS patients with high neurodegeneration have changes in B cells characterized by down-regulation of B-cell-specific genes and increased activation status" ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001402", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103", "http://www.disease-ontology.org/api/metadata/DOID:2377" ], "type": "yesno", "id": "58c0836102b8c6095300001c", "snippets": [ { "offsetInBeginSection": 1682, "offsetInEndSection": 1896, "text": "These results suggest that RRMS patients with radiological phenotypes showing high neurodegeneration have changes in B cells characterized by down-regulation of B-cell-specific genes and increased activation status", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26604134", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 744, "text": "Although the exact etiology is still obscure, the leading hypothesis behind MS relapses is acute inflammatory attacks on CNS myelin and axons. This complex process involves B and T cells together with macrophages and microglia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25620021", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 878, "text": "It is currently known that CD24 serves as a costimulatory factor of T cells that regulate their homeostasis and proliferation, while in B cells, CD24 is functionally involved in cell activation and differentiation. CD24 can enhance autoimmune diseases in terms of its protective role in the clonal deletion of autoreactive thymocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25666875", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 378, "text": "Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the CNS have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25895531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18388801", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "Interest in CD8+ T cells and B cells was initially inspired by observations in multiple sclerosis rather than in animal models: CD8+ T cells predominate in multiple sclerosis lesions, oligoclonal immunoglobulin bands in CSF have long been recognised as diagnostic and prognostic markers, and anti-B-cell therapies showed considerable efficacy in multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26724102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Differential effects of fingolimod on B-cell populations in multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24526661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25267439", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "B cells are increasingly recognized as major players in multiple sclerosis pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18474519", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 691, "text": "These observations underscore the B cell's contribution to the putative underpinnings of multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26857494", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 527, "text": "Data suggesting that B cells play a role in the pathogenesis of multiple sclerosis have been accumulating for the past five decades, demonstrating that the cerebrospinal fluid and central nervous system tissues of multiple sclerosis patients contain B cells, plasma cells, antibodies, and immunoglobulins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18388801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "B-cell-targeted treatment for multiple sclerosis: mechanism of action and clinical data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18388796", "endSection": "title" }, { "offsetInBeginSection": 161, "offsetInEndSection": 425, "text": "Subset composition and cytokine production of B cells derived from peripheral blood mononuclear cells from multiple sclerosis patients under Fingolimod treatment, untreated multiple sclerosis patients and healthy controls were analyzed by flow cytometry and ELISA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25750917", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 598, "text": "In particular, antigen presentation between B cells and T cells, increased trafficking of B cells across the blood-brain barrier, and autoantibodies produced by plasma cells may contribute to the pathophysiology of autoimmune disorders such as multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18388796", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 107, "text": "Accumulating evidence supports a major role of B cells in multiple sclerosis (MS) pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19996075", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1304, "text": "Further research is needed to elucidate the pathology of B cells and their role in central nervous system autoimmune diseases, including multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18388800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23634189", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 184, "text": "phingosine-1-phosphate receptors control B-cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia, and multiple sclerosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24679343", "endSection": "title" } ] }, { "body": "Which virus type causes Molluscum contagiosum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16390992", "http://www.ncbi.nlm.nih.gov/pubmed/23372568", "http://www.ncbi.nlm.nih.gov/pubmed/24155912", "http://www.ncbi.nlm.nih.gov/pubmed/18950398", "http://www.ncbi.nlm.nih.gov/pubmed/18616033", "http://www.ncbi.nlm.nih.gov/pubmed/9275219", "http://www.ncbi.nlm.nih.gov/pubmed/25186152", "http://www.ncbi.nlm.nih.gov/pubmed/9525670", "http://www.ncbi.nlm.nih.gov/pubmed/3814509", "http://www.ncbi.nlm.nih.gov/pubmed/22688765", "http://www.ncbi.nlm.nih.gov/pubmed/22301546", "http://www.ncbi.nlm.nih.gov/pubmed/8938977", "http://www.ncbi.nlm.nih.gov/pubmed/21802105", "http://www.ncbi.nlm.nih.gov/pubmed/26672647", "http://www.ncbi.nlm.nih.gov/pubmed/24491904", "http://www.ncbi.nlm.nih.gov/pubmed/881573", "http://www.ncbi.nlm.nih.gov/pubmed/23598933", "http://www.ncbi.nlm.nih.gov/pubmed/8850036", "http://www.ncbi.nlm.nih.gov/pubmed/24155550", "http://www.ncbi.nlm.nih.gov/pubmed/15284701", "http://www.ncbi.nlm.nih.gov/pubmed/21228810", "http://www.ncbi.nlm.nih.gov/pubmed/22262788", "http://www.ncbi.nlm.nih.gov/pubmed/10500212", "http://www.ncbi.nlm.nih.gov/pubmed/10502526", "http://www.ncbi.nlm.nih.gov/pubmed/25072249", "http://www.ncbi.nlm.nih.gov/pubmed/12552001" ], "ideal_answer": [ "Molluscum contagiosum virus (MCV) is a human poxvirus that causes tumor-like skin lesions." ], "exact_answer": [ "human poxvirus" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8867", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008977", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008976" ], "type": "factoid", "id": "58bfd0db02b8c60953000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Molluscum contagiosum virus (MCV), a poxvirus pathogenic for humans, replicates well in human skin in vivo, but not in vitro in standard monolayer cell cultures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22688765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Molluscum contagiosum virus (MCV) is a poxvirus that causes tumor-like skin lesions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21228810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Molluscum contagiosum poxvirus (MCV) type 1 and type 2 encode two chemokine-like proteins MC148R1 and MC148R2. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21802105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Molluscum contagiosum virus (MCV) is a common, human poxvirus that causes small papular skin lesions that persist for long periods without signs of inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10500212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "All poxviruses studied encode a type 1B topoisomerase that introduces transient nicks into DNA and thereby relaxes DNA supercoils. Here we present a study of the protein domains of the topoisomerase of the poxvirus molluscum contagiosum (MCV), which allows us to specify DNA contacts made by different domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10502526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Molluscum contagiosum virus (MCV) causes molluscum contagiosum (MC) in both children and adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8850036", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 357, "text": "MC54L, the IL-18 binding protein of the human poxvirus that causes molluscum contagiosum, is unique in having a C-terminal tail of nearly 100 amino acids that is dispensable for IL-18 binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12552001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Molluscum contagiosum is a common superficial skin infection caused by the poxvirus, Molluscum Contagiosum virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Molluscum contagiosum is a common skin and mucosal disease of viral origin, caused by molluscum contagiosum virus (MCV) virus of poxvirus family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23598933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Molluscum contagiosum is a benign contagious disease caused by a poxvirus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15284701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Molluscum contagiosum is a common superficial skin infection caused by the poxvirus, Molluscum Contagiosum virus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Molluscum contagiosum is a common skin and mucosal disease of viral origin, caused by molluscum contagiosum virus (MCV) virus of poxvirus family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23598933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Molluscum contagiosum is a viral infection of the skin and mucous membranes that is caused by infection with the molluscum contagiosum virus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18950398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Molluscum contagiosum (MC) is a very common benign self-limiting cutaneous viral infection caused by molluscum contagiosum virus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26672647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Molluscum contagiosum is caused by the molluscum contagiosum virus (MCV) and is a very common skin disorder mainly involving young children Cryotherapy, curettage or some topical therapies have been applied for MC, but all of these treatments need several sessions, can be somewhat ineffective, and very painful", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Molluscum contagiosum virus (MCV) causes an innocuous yet persistent skin infection in immunocompetent individuals and is spread by contact with lesions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25072249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Molluscum contagiosum virus (MCV) is a poxvirus that causes localized papules in healthy persons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22262788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Molluscum contagiosum is a virus that causes characteristic pearly lesions on the surface of the skin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18616033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Molluscum contagiosum virus (MCV) is a poxvirus that causes tumor-like skin lesions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21228810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Molluscum contagiosum virus is a human and animal dermatotropic pathogen, which causes a severe disease in immunocompromised individuals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24491904", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1313, "text": "Given that human diseases caused by poxviruses can be as lethal as smallpox or as benign as Molluscum contagiosum, and that vaccinia virus, the prototypic member of the pox family, persists as a mainstay of vaccine design and has potential as an oncolytic virus for tumor therapy, further research in this area remains important.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23372568", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 358, "text": "These cases support earlier evidence that the molluscum contagiosum virus may act as cases support earlier evidence that the molluscum contagiosum virus may act as an opportunistic pathogen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3814509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Molluscum contagiosum is a viral infection of the skin and mucous membranes that is caused by infection with the molluscum contagiosum virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18950398", "endSection": "abstract" } ] }, { "body": "Which disease(s) are caused by HEX A deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25606403", "http://www.ncbi.nlm.nih.gov/pubmed/20100466", "http://www.ncbi.nlm.nih.gov/pubmed/7717398", "http://www.ncbi.nlm.nih.gov/pubmed/2220809", "http://www.ncbi.nlm.nih.gov/pubmed/15108204", "http://www.ncbi.nlm.nih.gov/pubmed/9073025" ], "ideal_answer": [ "Mutations in the HEX A gene, encoding the alpha-subunit of beta-hexosaminidase A (Hex A), are the cause of Tay-Sachs disease as well as of juvenile, chronic, and adult GM2 gangliosidoses." ], "type": "summary", "id": "58cea0768acda34529000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder due to mutations in the HEXA gene resulting in a beta-hexosaminidase A (Hex A) deficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Rapid identification of HEXA mutations in Tay-Sachs patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20100466", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder caused by mutations in the HEXA gene resulting in \u03b2-hexosaminidase A (HEX A) deficiency and neuronal accumulation of GM2 ganglioside.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25606403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Tay-Sachs disease is a genetically determined neurodegenerative disorder, resulting from mutations of the hexosaminidase (Hex) A gene coding for the alpha-subunit of beta-D-N-acetyl-hexosaminidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9073025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Tay-Sachs disease (TSD) results from mutations in HEXA that cause Hex A deficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7717398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Mutations in the HEX A gene, encoding the alpha-subunit of beta-hexosaminidase A (Hex A), are the cause of Tay-Sachs disease as well as of juvenile, chronic, and adult GM2 gangliosidoses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2220809", "endSection": "abstract" } ] }, { "body": "What is Beh\u00e7et's disease", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22041429", "http://www.ncbi.nlm.nih.gov/pubmed/14761134", "http://www.ncbi.nlm.nih.gov/pubmed/26868128", "http://www.ncbi.nlm.nih.gov/pubmed/22310876", "http://www.ncbi.nlm.nih.gov/pubmed/12755969", "http://www.ncbi.nlm.nih.gov/pubmed/25447032", "http://www.ncbi.nlm.nih.gov/pubmed/10511031", "http://www.ncbi.nlm.nih.gov/pubmed/26740268", "http://www.ncbi.nlm.nih.gov/pubmed/25610186", "http://www.ncbi.nlm.nih.gov/pubmed/10195724", "http://www.ncbi.nlm.nih.gov/pubmed/27914129" ], "ideal_answer": [ "Behet's disease (BD) is a complex chronic relapsing inflammatory disorder of unknown etiology.", "Beh\u00e7et's disease (BD) is a complex chronic relapsing inflammatory disorder of unknown etiology.", "Beh\u00e7et's disease (BD) is a complex chronic relapsing inflammatory disorder of unknown etiology. ", "beh\u00e7et's disease (bd) is a complex chronic relapsing inflammatory disorder of unknown etiology." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001528", "http://www.disease-ontology.org/api/metadata/DOID:1670", "http://www.disease-ontology.org/api/metadata/DOID:13241" ], "type": "summary", "id": "58cb305c02b8c60953000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Beh\u00e7et's disease (BD) is a complex chronic relapsing inflammatory disorder of unknown etiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914129", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 227, "text": " Beh\u00e7et disease is a systemic disease of young adults characterized by venous occlusion in both the deep venous and retinal circulations. In severe ocular disease, blindness may occur despite immunosuppressive treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10511031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Beh\u00e7et disease is a chronic relapsing inflammatory disease affecting many different organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310876", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 232, "text": "Beh\u00e7et's disease is a multisystem disease featuring mucocutaneous, ocular, articular, vascular, intestinal, urogenital, and neurologic involvement and occurs with a high prevalence in the Mediterranean including Turkey. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12755969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Beh\u00e7et syndrome is a chronic disease hallmarked by inflammation of the blood vessels that is related to an autoimmune reaction caused by inherited susceptibility due to specific genes and environmental factors, probably components of infectious microorganisms, which turn on or get going the disease in genetically susceptible subjects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25447032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Beh\u00e7et disease (BD) is a rare relapsing, multisystem vasculitis characterised by recurrent oral and genital ulcers, and uveitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26740268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Beh\u00e7et's disease, also known as the Silk Road Disease, is a rare systemic vasculitis disorder of unknown etiology. Recurrent attacks of acute inflammation characterize Beh\u00e7et's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26868128", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 224, "text": "Beh\u00e7et's disease is a chronic multisystem vasculitis of unknown etiology that involves skin, mucous membranes, eyes, blood vessels, joints, central nervous system, digestive system, and occasionally other organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10195724", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 119, "text": "Behcet's disease is a multisystem inflammatory disorder, and its etiology has not been defined clearly yet. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25610186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Beh\u00e7et's disease is a systemic inflammatory disease presented with recurrent oral aphtha, cutaneous manifestations, uveitis, and genital ulcer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22041429", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 145, "text": "eh\u00e7et's disease is a systemic immunoinflammatory disease of young adults characterized by systemic vasculitis of arteries and veins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14761134", "endSection": "abstract" } ] }, { "body": "Does Yersinia pestis causes a respiratory infection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17041851", "http://www.ncbi.nlm.nih.gov/pubmed/26463167", "http://www.ncbi.nlm.nih.gov/pubmed/16239527", "http://www.ncbi.nlm.nih.gov/pubmed/21859946", "http://www.ncbi.nlm.nih.gov/pubmed/26123398", "http://www.ncbi.nlm.nih.gov/pubmed/25928467", "http://www.ncbi.nlm.nih.gov/pubmed/25974210", "http://www.ncbi.nlm.nih.gov/pubmed/16714568", "http://www.ncbi.nlm.nih.gov/pubmed/19629028", "http://www.ncbi.nlm.nih.gov/pubmed/12474416", "http://www.ncbi.nlm.nih.gov/pubmed/16964684", "http://www.ncbi.nlm.nih.gov/pubmed/24721571", "http://www.ncbi.nlm.nih.gov/pubmed/25691593" ], "ideal_answer": [ "Inhalation of Yersinia pestis results in primary pneumonic plague." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015010", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015007", "http://www.disease-ontology.org/api/metadata/DOID:0050069", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015009" ], "type": "yesno", "id": "58caf86f02b8c60953000030", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25691593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Yersinia pestis causes the fatal respiratory disease pneumonic plague.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26123398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Pulmonary infection by Yersinia pestis causes pneumonic plague, a rapidly progressing and often fatal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16714568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Pulmonary infection with the bacterium Yersinia pestis causes pneumonic plague, an often-fatal disease for which no vaccine is presently available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16239527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Yersinia pestis causes the fatal respiratory disease pneumonic plague", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26123398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Pneumonic plague is a deadly respiratory disease caused by Yersinia pestis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24721571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "On July 8, 2014, the Colorado Department of Public Health and Environment (CDPHE) laboratory identified Yersinia pestis, the bacterium that causes plague, in a blood specimen collected from a man (patient A) hospitalized with pneumonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25928467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Early emergence of Yersinia pestis as a severe respiratory pathogen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26123398", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The aerosol form of the bacterium Yersinia pestis causes the pneumonic plague, a rapidly fatal disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17041851", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 331, "text": " plague bacterium, Yersinia pestis, has historically been regarded as one of the deadliest pathogens known to mankind, having caused three major pandemics. After being transmitted by the bite of an infected flea arthropod vector, Y. pestis can cause three forms of human plague: bubonic, septicemic, and pneumonic,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21859946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 561, "text": "Plague is an infectious disease caused by the Yersinia pestis microorganism, which is transmitted to the human host from a natural reservoir (different rodent species) by a flea bite. Plague is still encountered in humans in the areas of its enzootic prevalence in local rodent populations. Infection by flea bite results in a bubonic or septicemic plague, possibly complicated by secondary pneumonia. The person with pneumonic symptoms may be a source of a droplet-borne inhalatory infection for other people who consequently develop primary pneumonic plague. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12474416", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 166, "text": "uring pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463167", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 582, "text": "In November 2006, the Uganda Ministry of Health received reports of an increase in bubonic plague cases and a possible outbreak of pneumonic plague among residents in the Arua and Nebbi districts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19629028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25974210", "endSection": "abstract" } ] }, { "body": "List 3 indications for Bupropion", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17227286", "http://www.ncbi.nlm.nih.gov/pubmed/9554323", "http://www.ncbi.nlm.nih.gov/pubmed/15479310", "http://www.ncbi.nlm.nih.gov/pubmed/16831112", "http://www.ncbi.nlm.nih.gov/pubmed/18219560", "http://www.ncbi.nlm.nih.gov/pubmed/16546007", "http://www.ncbi.nlm.nih.gov/pubmed/16027765", "http://www.ncbi.nlm.nih.gov/pubmed/21274361", "http://www.ncbi.nlm.nih.gov/pubmed/25661549", "http://www.ncbi.nlm.nih.gov/pubmed/25895022", "http://www.ncbi.nlm.nih.gov/pubmed/18619194", "http://www.ncbi.nlm.nih.gov/pubmed/10804045", "http://www.ncbi.nlm.nih.gov/pubmed/25223901", "http://www.ncbi.nlm.nih.gov/pubmed/27038550", "http://www.ncbi.nlm.nih.gov/pubmed/21142259", "http://www.ncbi.nlm.nih.gov/pubmed/26137782", "http://www.ncbi.nlm.nih.gov/pubmed/15155135", "http://www.ncbi.nlm.nih.gov/pubmed/12043548", "http://www.ncbi.nlm.nih.gov/pubmed/18264876", "http://www.ncbi.nlm.nih.gov/pubmed/23859696" ], "ideal_answer": [ "Bupropion is used to treat Obesity, for smoking cessation and for depression" ], "exact_answer": [ [ "weight loss in obesity" ], [ "smoking cessation" ], [ "depression" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016642", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016540", "http://www.biosemantics.org/jochem#4095874", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056687", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061485", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4276121", "http://www.biosemantics.org/jochem#4276121" ], "type": "list", "id": "58c1b2f702b8c6095300001e", "snippets": [ { "offsetInBeginSection": 407, "offsetInEndSection": 699, "text": " For genotype, genes associated with nicotinic acetylcholine receptors (nAChRs) and related proteins have been found to predict response to first-line medications (e.g. nicotine replacement therapy [NRT], bupropion, or varenicline) or quitting over time without a controlled treatment trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25895022", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1851, "text": "The approval of drug combinations, such as phentermine/topiramate and bupropion/naltrexone are also noteworthy, the components of which have been previously approved, but not necessarily for obesity as main indication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137782", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 374, "text": "Two drugs, phentermine plus topiramate and lorcaserin, have recently been approved by the US Food and Drug Administration for the indication of obesity; a third, bupropion plus naltrexone, is under consideration for approval. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25223901", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1312, "text": "Bupropion SR is preferred to subjects with depression or smokers who have failed with the previous two agents, due to the many contra-indications and side effects of bupropion SR. With one of the 3 agents combined with follow-up visits with counselling, one can expect a 1-year quit rate around 20-25%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18619194", "endSection": "abstract" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1211, "text": "In vitro intrinsic clearances were likewise different for bupropion enantiomers.CONCLUSIONS: Stereoselective bupropion hydroxylation may have implications for the therapeutic efficacy of bupropion as an antidepressant or smoking cessation therapy, and for the use of bupropion as an in vivo phenotypic probe for CYP2B6 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18219560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "PURPOSE: Hydroxylation of the antidepressant and smoking deterrent drug bupropion is a clinically important bioactivation and elimination pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18219560", "endSection": "abstract" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 2003, "text": "Although not U.S. Food and Drug Administration approved for these indications, bupropion has also been used as an adjunctive treatment to reverse antidepressant-induced sexual dysfunction and to augment anti-depressant efficacy in partial responders and non-responders to other agents.Bupropion has played and will continue to play an important role as a treatment for major depressive disorder in adults, as well as for other related disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16027765", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1358, "text": "Clinically, bupropion is used as a treatment for two indications, as an antidepressant, the indication for which it was developed, and as a tobacco use cessation agent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17227286", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 129, "text": "Sustained release bupropion (amfebutamone) is a non-nicotine agent that is indicated as an aid to smoking cessation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10804045", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 215, "text": "Bupropion was introduced for smoking cessation following a pivotal trial showing that it gave improved efficacy over the nicotine patch and also suggesting combination treatment was beneficial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23859696", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 285, "text": "Compared with a placebo control, bupropion approximately doubles smoking quit rates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16831112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Over the past decade, bupropion has become a major pharmacotherapy for smoking cessation in the Western world. Unlike other smoking cessation pharmacotherapies, bupropion is a non-nicotine treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16831112", "endSection": "abstract" }, { "offsetInBeginSection": 2079, "offsetInEndSection": 2247, "text": "Bupropion has been tested in over 40 controlled clinical trials and has been associated with higher rates of treatment discontinuation due to adverse events than NRTs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21142259", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 875, "text": "Bupropion SR is a useful oral and non-nicotine form of pharmacotherapy for smoking cessation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12043548", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 549, "text": "everal new drugs for the treatment of obesity are either licensed in some parts of the world, submitted for registration, or completing phase III trials. These include combinations (at low dose) of existing drugs, e.g., bupropion + naltrexone (Contrave),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25661549", "endSection": "abstract" } ] }, { "body": "What is the function of BAX", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19138672", "http://www.ncbi.nlm.nih.gov/pubmed/12732850", "http://www.ncbi.nlm.nih.gov/pubmed/17494694", "http://www.ncbi.nlm.nih.gov/pubmed/24712408", "http://www.ncbi.nlm.nih.gov/pubmed/27164337", "http://www.ncbi.nlm.nih.gov/pubmed/8798665", "http://www.ncbi.nlm.nih.gov/pubmed/17519046", "http://www.ncbi.nlm.nih.gov/pubmed/23744350", "http://www.ncbi.nlm.nih.gov/pubmed/24503763", "http://www.ncbi.nlm.nih.gov/pubmed/21069436", "http://www.ncbi.nlm.nih.gov/pubmed/11932420", "http://www.ncbi.nlm.nih.gov/pubmed/22442658", "http://www.ncbi.nlm.nih.gov/pubmed/11340567", "http://www.ncbi.nlm.nih.gov/pubmed/17074758", "http://www.ncbi.nlm.nih.gov/pubmed/16679323", "http://www.ncbi.nlm.nih.gov/pubmed/23784543", "http://www.ncbi.nlm.nih.gov/pubmed/20885444", "http://www.ncbi.nlm.nih.gov/pubmed/23475110", "http://www.ncbi.nlm.nih.gov/pubmed/19680558", "http://www.ncbi.nlm.nih.gov/pubmed/24269152", "http://www.ncbi.nlm.nih.gov/pubmed/8600029", "http://www.ncbi.nlm.nih.gov/pubmed/8887678", "http://www.ncbi.nlm.nih.gov/pubmed/20723427", "http://www.ncbi.nlm.nih.gov/pubmed/9565621", "http://www.ncbi.nlm.nih.gov/pubmed/25497728", "http://www.ncbi.nlm.nih.gov/pubmed/12213925", "http://www.ncbi.nlm.nih.gov/pubmed/26395559", "http://www.ncbi.nlm.nih.gov/pubmed/15642728", "http://www.ncbi.nlm.nih.gov/pubmed/18547146", "http://www.ncbi.nlm.nih.gov/pubmed/26252372", "http://www.ncbi.nlm.nih.gov/pubmed/10669738" ], "ideal_answer": [ "BAX is a central death regulator that controls apoptosis in normal and cancer cells", "pro-apoptotic protein Bax" ], "exact_answer": [ "bax promotes Apoptosis" ], "concepts": [ "http://www.uniprot.org/uniprot/BAX_ECOLI", "http://amigo.geneontology.org/amigo/term/GO:0065009", "http://www.uniprot.org/uniprot/BAX_BOVIN", "http://www.uniprot.org/uniprot/BAX_RAT", "http://www.uniprot.org/uniprot/BAX_HUMAN", "http://www.uniprot.org/uniprot/BAX_MOUSE" ], "type": "factoid", "id": "58bde18b02b8c60953000014", "snippets": [ { "offsetInBeginSection": 545, "offsetInEndSection": 570, "text": "pro-apoptotic protein Bax", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Bax, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major proapoptotic member of the B-cell lymphoma 2 (Bcl-2) family proteins that control apoptosis in normal and cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26395559", "endSection": "abstract" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1620, "text": "Thus, PP2A may function as a physiological Bax regulatory phosphatase that not only dephosphorylates Bax but also activates its proapoptotic function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16679323", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 769, "text": "The ability of the mutants to protect against Bax-mediated cell death is divided into three groups: (1) group I, retention of anti-Bax function in both the Val129 and Met129 mutants; (2) group II, retention of anti-Bax function only in Val129 mutants; and (3) group III, reduction or no anti-Bax function in Val129 and Met129 mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17494694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "A popular model of BCL-2 and BAX involvement in apoptosis suggests that upon apoptosis induction cytosolic BAX translocates to the mitochondria, where it displays the pro-apoptotic function, which involves its homodimerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11340567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 572, "text": "The purpose of this study was to investigate the expression of the gene coding for the antiapoptotic molecule Bcl-2, the proapoptotic molecule Bax, and the apoptosis executor enzyme caspase-3 in preimplantation renal biopsies (PIB) as markers for delayed graft function.In this prospective single-center study, gene expression levels were evaluated using real-time TaqMan polymerase chain reaction in PIB of kidneys from 72 deceased donors (DDs) and 18 living donors (LDs).CASP3 and BAX expression levels were higher, whereas those of BCL2 were lower, in DD than in LD PIB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24503763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The function Bax and/or Bak in constituting a gateway for mitochondrial apoptosis in response to apoptotic stimuli has been unequivocally demonstrated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23784543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Bax is a major proapoptotic member of the Bcl2 family that is required for apoptotic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16679323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Bax is a proapoptotic member of the Bcl-2 family of proteins which localizes to and uses mitochondria as its major site of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10669738", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 121, "text": "death-promoting Bax protein", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8600029", "endSection": "title" }, { "offsetInBeginSection": 97, "offsetInEndSection": 178, "text": "The suppressors function through heterodimerization with the death promoters, Bax", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8798665", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1024, "text": "Bax- and Bak-mediated apoptosis severely limits adenoviral replication,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11932420", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 275, "text": "Bax a pro-apoptotic member localizes as monomers in the cytosol of healthy cells and accumulates as oligomers in mitochondria of apoptotic cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17519046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Bax and Bak (Bax/Bak) are essential pro-apoptotic proteins of the Bcl-2 family that trigger mitochondrial outer membrane permeabilization (MOMP) in a Bcl-2/Bcl-xL-inhibitable manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "BAX protein plays a key role in the mitochondria-mediated apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25497728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The multi-BCL-2 homology domain pro-apoptotic BCL-2 family members BAK and BAX have critical roles in apoptosis. They are essential for mitochondrial outer-membrane permeabili", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23744350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Members of the Bcl-2 family play key roles as proapoptotic (e.g., Bax) and antiapoptotic (e.g., Bcl-x(L)) regulators of programmed cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20885444", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 138, "text": "The Bcl-2 associated X protein (Bax), belonging to the Bcl-2 family, plays a pivotal role in mitochondria-dependent apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20723427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 36, "text": "The murine proapoptotic protein Bax ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12213925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Bax is a pro-apoptotic member of the Bcl-2 family proteins involved in the release of apoptogenic factors from mitochondria to the cytosol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19138672", "endSection": "abstract" }, { "offsetInBeginSection": 50, "offsetInEndSection": 176, "text": "activated Bax forms large oligomers that permeabilize the outer mitochondrial membrane, thereby committing cells to apoptosis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18547146", "endSection": "abstract" } ] }, { "body": "What is the link between Ctf4 and Chl1 in cohesion establishment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "http://www.ncbi.nlm.nih.gov/pubmed/27397686", "http://www.ncbi.nlm.nih.gov/pubmed/23036200" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513031343534001D", "o": "CTF4" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1427963", "o": "http://linkedlifedata.com/resource/umls/label/A20695577" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/uniprot/Q01454", "o": "http://purl.uniprot.org/uniprot/Q01454" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q01454", "o": "http://linkedlifedata.com/resource/#_513031343534001D" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/uniprot/Q01454", "o": "CTF4_YEAST" } ], "ideal_answer": [ "Ctf4 links DNA replication with sister chromatid cohesion establishment by recruiting the Chl1 helicase to the replisome. The Eco1 acetyltransferase, helped by factors including Ctf4 and Chl1, concomitantly acetylates the chromosomal cohesin complex to stabilize its cohesive links.", "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3. Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0034089", "http://www.biosemantics.org/jochem#4264134", "http://amigo.geneontology.org/amigo/term/GO:0034085", "http://amigo.geneontology.org/amigo/term/GO:0034087", "http://www.biosemantics.org/jochem#4265011" ], "type": "summary", "id": "587f8324d8d850a152000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Ctf4 Links DNA Replication with Sister Chromatid Cohesion Establishment by Recruiting the Chl1 Helicase to the Replisome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27397686", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 441, "text": "The Eco1 acetyltransferase, helped by factors including Ctf4 and Chl1, concomitantly acetylates the chromosomal cohesin complex to stabilize its cohesive links. Here we show that Ctf4 recruits the Chl1 helicase to the replisome via a conserved interaction motif that Chl1 shares with GINS and polymerase \u03b1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27397686", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 1079, "text": "The Chl1 helicase facilitates replication fork progression under conditions of nucleotide depletion, partly independently of Ctf4 interaction. Conversely, Ctf4 interaction, but not helicase activity, is required for Chl1's role in sister chromatid cohesion. A physical interaction between Chl1 and the cohesin complex during S phase suggests that Chl1 contacts cohesin to facilitate its acetylation. Our results reveal how Ctf4 forms a replisomal interaction hub that coordinates replication fork progression and sister chromatid cohesion establishment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27397686", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 858, "text": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036200", "endSection": "abstract" }, { "offsetInBeginSection": 1319, "offsetInEndSection": 1490, "text": "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 629, "text": "We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1002, "text": "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1499, "text": "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1497, "text": "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 630, "text": "We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 860, "text": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "endSection": "title" }, { "offsetInBeginSection": 633, "offsetInEndSection": 862, "text": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23036200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Ctf4 Links DNA Replication with Sister Chromatid Cohesion Establishment by Recruiting the Chl1 Helicase to the Replisome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27397686", "endSection": "title" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1500, "text": "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1007, "text": "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "endSection": "abstract" } ] }, { "body": "How is primary intestinal lymphangiectasia (PIL) caused?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19853733", "http://www.ncbi.nlm.nih.gov/pubmed/26217101", "http://www.ncbi.nlm.nih.gov/pubmed/26962779", "http://www.ncbi.nlm.nih.gov/pubmed/8650761", "http://www.ncbi.nlm.nih.gov/pubmed/23229460", "http://www.ncbi.nlm.nih.gov/pubmed/23316917", "http://www.ncbi.nlm.nih.gov/pubmed/24449480", "http://www.ncbi.nlm.nih.gov/pubmed/23626516", "http://www.ncbi.nlm.nih.gov/pubmed/26405709", "http://www.ncbi.nlm.nih.gov/pubmed/18855225", "http://www.ncbi.nlm.nih.gov/pubmed/16292099", "http://www.ncbi.nlm.nih.gov/pubmed/22110841", "http://www.ncbi.nlm.nih.gov/pubmed/19887697", "http://www.ncbi.nlm.nih.gov/pubmed/18294365", "http://www.ncbi.nlm.nih.gov/pubmed/23180957", "http://www.ncbi.nlm.nih.gov/pubmed/26908672", "http://www.ncbi.nlm.nih.gov/pubmed/25943403", "http://www.ncbi.nlm.nih.gov/pubmed/20812055", "http://www.ncbi.nlm.nih.gov/pubmed/26169531" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1418580", "o": "http://linkedlifedata.com/resource/umls/label/A12036259" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12036259", "o": "PIL" } ], "ideal_answer": [ "Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008201", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008200", "http://www.disease-ontology.org/api/metadata/DOID:2402", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007413", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007410", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007422", "http://www.disease-ontology.org/api/metadata/DOID:5295" ], "type": "summary", "id": "58ca5cba02b8c6095300002b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 390, "text": "Primary intestinal lymphangiectasia (PIL) is a rare disorder of unknown etiology characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26962779", "endSection": "abstract" }, { "offsetInBeginSection": 1778, "offsetInEndSection": 1879, "text": "PIL, effusions, and lymphedema can be the features of multisegmental generalized lymphatic dysplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26962779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23180957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Primary intestinal lymphangiectasia is a rare cause of protein-losing enteropathy and usually presents with intermittent diarrhea or malnutrition. Diagnosis depends largely on its pathologic condition demonstrating greatly dilated lymphatics mainly in the lamina propria of the mucosa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19853733", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 762, "text": "The histopathologic condition of the resected small intestine showed lymphatic dilation limited mainly to the subserosa and mesentery but was not prominent in the mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19853733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lymphatics and the development of protein-losing enteropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22110841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is an exudative enteropathy resulting from morphologic abnormalities in the intestinal lymphatics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26908672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Primary intestinal lymphangiectasia (PIL), so-called Waldmann's disease, is an uncommon condition, characterized by dilated intestinal submucosal and subserosal lymphatics of the gastrointestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16292099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18294365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20812055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Primary intestinal lymphangiectasia (PIL) is a protein-losing, exsudative gastroenteropathy causing lymphatic obstruction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Primary intestinal lymphangiectasia (PIL) is a protein-losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24449480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Exudative enteropathy secondary to primary intestinal lymphangiectasia (PIL) is characterized by lymphopenia, hypogammaglobulinemia and hypoalbuminemia resulting from leakage of lymph fluid into the intestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18855225", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26217101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Primary intestinal lymphangiectasia (PIL) is a protein-losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24449480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Primary intestinal lymphangiectasia (PIL), so-called Waldmanns disease, is an uncommon condition, characterized by dilated intestinal submucosal and subserosal lymphatics of the gastrointestinal tract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16292099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Primary intestinal lymphangiectasia (Waldmanns disease) is a rare disease characterized by dilated lymphatics in the small bowel leading to an exudative enteropathy with lymphopenia, hypoalbuminemia and hypogammaglobulinemia.We report the case of a 23 year-old male who presented with chronic anemia and in whom primary intestinal lymphangiectasia was diagnosed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26405709", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 367, "text": "We report a series of 4 children from Chennai, India presenting with anasarca, recurrent diarrhea, hypoproteinemia and confirmatory features of PIL on endoscopy and histopathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19887697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Primary intestinal lymphangiectasia (PIL) is a protein-losing, exsudative gastroenteropathy causing lymphatic obstruction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by a congenital malformation of the lymphatic vessels of the small intestine causing insufficient drainage and leakage of lymph fluid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25943403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26217101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Primary intestinal lymphangiectasia (PIL) or Waldmann's disease is a rare protein-losing gastroenteropathy of unknown etiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23626516", "endSection": "abstract" } ] }, { "body": "What are congenital disorders of glycosylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26873821", "http://www.ncbi.nlm.nih.gov/pubmed/27725718", "http://www.ncbi.nlm.nih.gov/pubmed/25840006", "http://www.ncbi.nlm.nih.gov/pubmed/26238249", "http://www.ncbi.nlm.nih.gov/pubmed/24157261" ], "ideal_answer": [ "Congenital disorders of glycosylation (CDG) are a growing group of inherited metabolic disorders where enzymatic defects in the formation or processing of glycolipids and/or glycoproteins lead to variety of different diseases.\nMore than 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today.\t\nThe patients have hundreds of misglycosylated products, which afflict a myriad of processes, including cell signaling, cell-cell interaction, and cell migration." ], "type": "summary", "id": "58e115d66fddd3e83e00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Congenital disorder of glycosylation (CDG), formerly representing a group of diseases due to defects in the biosynthetic pathway of protein N-glycosylation, currently covers a wide range of disorders affecting glycoconjugates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26873821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Congenital disorders of glycosylation form a rapidly growing group of inherited metabolic diseases. As glycosylation affects proteins all over the organism, a mutation in a single gene leads to a multisystemic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26238249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 539, "text": "Glycosylation is an integral part in health and disease, as emphasized by the growing number of identified glycosylation defects. In humans, proteins are modified with a diverse range of glycoforms synthesized in complex biosynthetic pathways. Glycosylation disorders have been described in congenital disorders of glycosylation (CDG) as well as in acquired disease conditions such and non-alcoholic fatty liver disease (NAFLD). A hallmark in a subset of CDG cases is the reduced glycosylation site occupancy of asparagine-linked glycans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27725718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Congenital disorders of glycosylation (CDG) are a growing group of inherited metabolic disorders where enzymatic defects in the formation or processing of glycolipids and/or glycoproteins lead to variety of different diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157261", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 354, "text": " More than 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840006", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 880, "text": "The patients have hundreds of misglycosylated products, which afflict a myriad of processes, including cell signaling, cell-cell interaction, and cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840006", "endSection": "abstract" } ] }, { "body": "Which are the additions of the JASPAR 2016 open-access database of transcription factor binding profiles?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26531826" ], "ideal_answer": [ "Compared to the JASPAR CORE collection, JASPAR 2016 has been expanded with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and 59 profiles (58 in vertebrates and 1 in fungi) have been updated. The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. The structural annotation of the TF DNA binding domains (DBDs) has been updated following a published hierarchical structural classification. In addition, 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites were introduced . The new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, users are provided with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. JASPAR2016 R/Bioconductor data package is also provided with the data of this release." ], "exact_answer": [ [ "494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi)" ], [ "Updated structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification" ], [ "130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites" ], [ "A new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence" ], [ "A Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles" ], [ "JASPAR2016 R/Bioconductor data package" ] ], "type": "list", "id": "587d2b7efe8a08052f000003", "snippets": [ { "offsetInBeginSection": 267, "offsetInEndSection": 1301, "text": "For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26531826", "endSection": "abstract" } ] }, { "body": "What is the function of the protein tafazzin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24318983", "http://www.ncbi.nlm.nih.gov/pubmed/25598000", "http://www.ncbi.nlm.nih.gov/pubmed/25118650", "http://www.ncbi.nlm.nih.gov/pubmed/26415690", "http://www.ncbi.nlm.nih.gov/pubmed/21068380", "http://www.ncbi.nlm.nih.gov/pubmed/25941633", "http://www.ncbi.nlm.nih.gov/pubmed/24714493", "http://www.ncbi.nlm.nih.gov/pubmed/24858921", "http://www.ncbi.nlm.nih.gov/pubmed/25688091", "http://www.ncbi.nlm.nih.gov/pubmed/19700766", "http://www.ncbi.nlm.nih.gov/pubmed/25919711", "http://www.ncbi.nlm.nih.gov/pubmed/16794186", "http://www.ncbi.nlm.nih.gov/pubmed/25247053", "http://www.ncbi.nlm.nih.gov/pubmed/17082194" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0031843", "o": "function" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0031843", "o": "http://linkedlifedata.com/resource/umls/label/A3879881" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3879881", "o": "function" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1336578", "o": "http://linkedlifedata.com/resource/umls/label/A12030635" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12030635", "o": "TAFAZZIN" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1336578", "o": "TAZ" } ], "ideal_answer": [ "Tafazzin is a phospholipid transacylase that transfers acyl chains with unsaturated fatty acids from phospholipids to monolysocardiolipin to generate cardiolipin with unsaturated fatty acids on mitochondrial membrane." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.disease-ontology.org/api/metadata/DOID:0050476", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056889" ], "type": "summary", "id": "58d90b968acda3452900000e", "snippets": [ { "offsetInBeginSection": 104, "offsetInEndSection": 282, "text": "Tafazzin is a transacylase that transfers acyl chains with unsaturated fatty acids from phospholipids to monolysocardiolipin to generate cardiolipin with unsaturated fatty acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25688091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Tafazzin (EC 2.3.1.23) is a Phospholipid Transacylase involved in Cardiolipin remodeling on mitochondrial membrane and coded by TAZ gene (Cytogenetic Location: Xq28) in human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25118650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Tafazzin is a transacylase that affects cardiolipin fatty acid composition and mitochondrial function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25598000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause Barth syndrome (BTHS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25941633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Tafazzin (TAZ) is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25919711", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 479, "text": "Tafazzin expression induced a new enzymatic function in Sf9 cell mitochondria, namely 1-palmitoyl-2-[14C]linoleoyl-phosphatidylcholine:monolysocardiolipin linoleoyltransferase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17082194", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 897, "text": "Among the human isoforms, only full-length tafazzin (FL) and tafazzin lacking exon 5 (Delta5) had transacylase activity, and only these two isoforms were able to restore a normal cardiolipin pattern, normal respiratory activity of mitochondria, and male fertility in tafazzin-deficient flies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19700766", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 288, "text": "Tafazzin is a mitochondrial transacylase required for cardiolipin remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21068380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Tafazzin is a putative enzyme that is involved in cardiolipin metabolism, it may carry mutations responsible for Barth syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17082194", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 790, "text": "Tafazzin is an enzyme that remodels saturated fatty acyl chains within CL to unsaturated fatty acyl chains, loss of function mutations in the TAZ gene encoding tafazzin are causal for the inherited cardiomyopathy Barth syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26415690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The tafazzin gene encodes a phospholipid-lysophospholipid transacylase involved in cardiolipin metabolism, but it is not known why it forms multiple transcripts as a result of alternative splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19700766", "endSection": "abstract" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1684, "text": "Furthermore, the data show that the expression of human tafazzin in flies creates cardiolipin with a Drosophila pattern, suggesting that the characteristic fatty acid profile of cardiolipin is not determined by the substrate specificity of tafazzin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19700766", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Tafazzin is a transacylase that affects cardiolipin fatty acid composition and mitochondrial function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25598000", "endSection": "abstract" } ] }, { "body": "What are assassin bugs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25996956", "http://www.ncbi.nlm.nih.gov/pubmed/24438295", "http://www.ncbi.nlm.nih.gov/pubmed/25689825", "http://www.ncbi.nlm.nih.gov/pubmed/26249492", "http://www.ncbi.nlm.nih.gov/pubmed/27058599", "http://www.ncbi.nlm.nih.gov/pubmed/24884699" ], "ideal_answer": [ "The family Reduviidae (Hemiptera: Heteroptera), or assassin bugs, is among the most diverse families of the true bugs, with more than 6,000 species." ], "type": "summary", "id": "58e12ea66fddd3e83e00000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The complete mitochondrial genome of an assassin bug Peirates arcuatus (Hemiptera: Reduviidae).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24438295", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "First complete mitochondrial genome sequence from the tribelocephaline assassin bugs (Hemiptera: Reduviidae).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25996956", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The complete mitochondrial genome (mitogenome) of Opistoplatys sp. was determined, which was the first representation from the assassin bug subfamily Tribelocephalinae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25996956", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 160, "text": "The family Reduviidae (Hemiptera: Heteroptera), or assassin bugs, is among the most diverse families of the true bugs, with more than 6,000 species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27058599", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Comparative mitogenomics of the assassin bug genus Peirates (Hemiptera: Reduviidae: Peiratinae) ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25689825", "endSection": "title" } ] }, { "body": "Are the genes for marneral biosynthesis scattered in the genome of A. thaliana?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22561113", "http://www.ncbi.nlm.nih.gov/pubmed/21876149" ], "ideal_answer": [ "These clusters are unlikely to have arisen by horizontal gene transfer, and the mechanisms behind their formation are poorly understood. Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation.", "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation. ", "Genes for marneral synthesis are organized in an operon-like gene cluster in thale cress (A. thaliana)." ], "exact_answer": "no", "type": "yesno", "id": "58eb7898eda5a57672000006", "snippets": [ { "offsetInBeginSection": 1064, "offsetInEndSection": 1284, "text": "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876149", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1278, "text": "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876149", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1063, "text": "Previously in thale cress (Arabidopsis thaliana) we identified an operon-like gene cluster that is required for the synthesis and modification of the triterpene thalianol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561113", "endSection": "title" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1286, "text": "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876149", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1155, "text": "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876149", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 447, "text": "the cyclic hydroxamic acid pathways in maize, the avenacin biosynthesis gene clusters in oat, the thalianol pathway in Arabidopsis thaliana, and the diterpenoid momilactone cluster in rice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22561113", "endSection": "title" } ] }, { "body": "Is Dupilumab used for treatment of atopic dermatitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27334730", "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "http://www.ncbi.nlm.nih.gov/pubmed/26836729", "http://www.ncbi.nlm.nih.gov/pubmed/27497276", "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "http://www.ncbi.nlm.nih.gov/pubmed/27906698" ], "ideal_answer": [ "Yes, patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity." ], "exact_answer": "yes", "type": "yesno", "id": "58df3e408acda3452900002d", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 149, "text": "Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26836729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "endSection": "title" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1161, "text": "Dupilumab is a biologic agent targeted at TH2 cytokines, but indirectly impacts IgE and is an important biologic agent for atopic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Dupilumab for the treatment of atopic dermatitis: A clinical trial review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "endSection": "title" }, { "offsetInBeginSection": 143, "offsetInEndSection": 255, "text": "Dupilumab is a novel monoclonal antibody that was recently studied in adult patients with moderate-to-severe AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "endSection": "abstract" }, { "offsetInBeginSection": 2339, "offsetInEndSection": 2472, "text": "Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 978, "text": "The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "endSection": "abstract" } ] }, { "body": "Where is base J found in the genome of Leishmania tarentolae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25662217", "http://www.ncbi.nlm.nih.gov/pubmed/17329373", "http://www.ncbi.nlm.nih.gov/pubmed/19114062", "http://www.ncbi.nlm.nih.gov/pubmed/10562569", "http://www.ncbi.nlm.nih.gov/pubmed/25104019", "http://www.ncbi.nlm.nih.gov/pubmed/20215442" ], "ideal_answer": [ "Base J (\u03b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei.", "Base J (-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei. J is enriched at sites involved in RNA polymerase (RNAP) II initiation and termination. ", "Base J (\u00ce\u00b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei.", "Base J (\u03b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops.", "j (\u03b2-d-glucosyl-hydroxymethyluracil) replaces 1% of t in the leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. . j is found predominantly in repetitive dna and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in trypanosoma brucei. . ", "base j (\u03b2-d-glucosyl-hydroxymethyluracil) replaces 1% of t in the leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops." ], "exact_answer": [ "telomeric repeats" ], "type": "factoid", "id": "58cf5c5a8acda34529000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Base J (\u03b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25662217", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 266, "text": "Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10562569", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 242, "text": "J is enriched at sites involved in RNA polymerase (RNAP) II initiation and termination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25104019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Base J (\u03b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25662217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Telomeric localization of the modified DNA base J in the genome of the protozoan parasite Leishmania", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17329373", "endSection": "title" }, { "offsetInBeginSection": 107, "offsetInEndSection": 267, "text": "Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10562569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Base J is a hypermodified DNA base localized primarily to telomeric regions of the genome of Trypanosoma brucei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20215442", "endSection": "abstract" } ] }, { "body": "Which tool is available for predicting regulatory interactions from ChIP-seq data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27924029" ], "ideal_answer": [ "CisMapper predicts the regulatory targets of a TF using the correlation between a histone mark at the TF's bound sites and the expression of each gene across a panel of tissues. CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression. CisMapper also predicts which TF binding sites regulate a given gene more accurately than using genomic distance. Unlike distance-based methods, CisMapper can predict which transcription start site of a gene is regulated by a particular binding site of the TF." ], "exact_answer": [ "CisMapper" ], "type": "factoid", "id": "587e0116ae05ffb474000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "CisMapper: predicting regulatory interactions from transcription factor ChIP-seq data", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924029", "endSection": "title" }, { "offsetInBeginSection": 546, "offsetInEndSection": 741, "text": "We present CisMapper, which predicts the regulatory targets of a TF using the correlation between a histone mark at the TF's bound sites and the expression of each gene across a panel of tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924029", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 1077, "text": "Using both chromatin conformation capture and differential expression data, we show that CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924029", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1338, "text": " CisMapper also predicts which TF binding sites regulate a given gene more accurately than using genomic distance. Unlike distance-based methods, CisMapper can predict which transcription start site of a gene is regulated by a particular binding site of the TF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "CisMapper: predicting regulatory interactions from transcription factor ChIP-seq data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924029", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "CisMapper: predicting regulatory interactions from transcription factor ChIP-seq data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924029", "endSection": "title" }, { "offsetInBeginSection": 742, "offsetInEndSection": 1078, "text": "Using both chromatin conformation capture and differential expression data, we show that CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924029", "endSection": "abstract" } ] }, { "body": "Where are the unipolar brush cells localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7978355", "http://www.ncbi.nlm.nih.gov/pubmed/11457596", "http://www.ncbi.nlm.nih.gov/pubmed/8177517", "http://www.ncbi.nlm.nih.gov/pubmed/9923978", "http://www.ncbi.nlm.nih.gov/pubmed/14614902", "http://www.ncbi.nlm.nih.gov/pubmed/8059339", "http://www.ncbi.nlm.nih.gov/pubmed/19409228", "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "http://www.ncbi.nlm.nih.gov/pubmed/9193142", "http://www.ncbi.nlm.nih.gov/pubmed/11396855", "http://www.ncbi.nlm.nih.gov/pubmed/11044898", "http://www.ncbi.nlm.nih.gov/pubmed/12655510", "http://www.ncbi.nlm.nih.gov/pubmed/17223277", "http://www.ncbi.nlm.nih.gov/pubmed/16289944", "http://www.ncbi.nlm.nih.gov/pubmed/8300904", "http://www.ncbi.nlm.nih.gov/pubmed/16344141", "http://www.ncbi.nlm.nih.gov/pubmed/8821458", "http://www.ncbi.nlm.nih.gov/pubmed/17409247", "http://www.ncbi.nlm.nih.gov/pubmed/7673463", "http://www.ncbi.nlm.nih.gov/pubmed/9023728", "http://www.ncbi.nlm.nih.gov/pubmed/15940501", "http://www.ncbi.nlm.nih.gov/pubmed/12814190", "http://www.ncbi.nlm.nih.gov/pubmed/20937306", "http://www.ncbi.nlm.nih.gov/pubmed/7472327", "http://www.ncbi.nlm.nih.gov/pubmed/21190007" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0392752", "o": "Localized" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0392752", "o": "http://linkedlifedata.com/resource/umls/label/A0428112" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0428112", "o": "LOCALIZED" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0392752", "o": "http://linkedlifedata.com/resource/umls/label/A7581226" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7581226", "o": "Localized" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0392752", "o": "http://linkedlifedata.com/resource/umls/label/A6833253" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6833253", "o": "Localized" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0392752", "o": "http://linkedlifedata.com/resource/umls/label/A18656681" } ], "ideal_answer": [ "Unipolar brush cells (UBCs) are glutamatergic interneurons localized in granule cell regions of the cochlear nucleus and the vestibulocerebellum of cerebellum." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ], "type": "summary", "id": "58c67bf302b8c60953000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Cerebellar unipolar brush cells (UBCs) are glutamatergic interneurons that receive direct input from vestibular afferents in the form of a unique excitatory synapse on their dendritic brush. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17409247", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 677, "text": "Immunostained unipolar brush cells were observed in granule cell regions of the cochlear nucleus and the vestibulocerebellum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8821458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Postsynaptic enrichment of Eps8 at dendritic shaft synapses of unipolar brush cells in rat cerebellum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17223277", "endSection": "title" }, { "offsetInBeginSection": 749, "offsetInEndSection": 874, "text": "In cerebellum, unipolar brush cells (UBCs) were densely Eps8 immunopositive and granule cells were moderately immunostained. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17223277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Postnatal differentiation of unipolar brush cells and mossy fiber-unipolar brush cell synapses in rat cerebellum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11457596", "endSection": "title" }, { "offsetInBeginSection": 485, "offsetInEndSection": 725, "text": "Knowledge of the ultrastructure of the unipolar brush cell terminals and of the cellular identity of its postsynaptic targets is required to understand how unipolar brush cells contribute to information processing in the cerebellar circuit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1001, "text": "To investigate the unipolar brush cell axon and its targets, unipolar brush cells were patch-clamped in fresh parasagittal slices from rat cerebellar vermis with electrodes filled with Lucifer Yellow and Biocytin, and examined by confocal fluorescence and electron microscopy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Calretinin-immunoreactive unipolar brush cells in the developing human cerebellum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16289944", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Unipolar brush cell: a potential feedforward excitatory interneuron of the cerebellum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "title" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1160, "text": "Unipolar brush cells are also found in the cochlear nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7978355", "endSection": "abstract" }, { "offsetInBeginSection": 1783, "offsetInEndSection": 1856, "text": "The unipolar brush cells reside nearly exclusively in the granular layer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7978355", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1249, "text": "In the monkey cerebellum, unipolar brush cells, localized in the granular layer, were heavily labeled, whereas Golgi cells were devoid of NG", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12655510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Unipolar brush cells (UBC) are small, glutamatergic neurons residing in the granular layer of the cerebellar cortex and the granule cell domain of the cochlear nuclear complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20937306", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 727, "text": "Knowledge of the ultrastructure of the unipolar brush cell terminals and of the cellular identity of its postsynaptic targets is required to understand how unipolar brush cells contribute to information processing in the cerebellar circuit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 1004, "text": "To investigate the unipolar brush cell axon and its targets, unipolar brush cells were patch-clamped in fresh parasagittal slices from rat cerebellar vermis with electrodes filled with Lucifer Yellow and Biocytin, and examined by confocal fluorescence and electron microscopy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 521, "text": "While granule cells express solely VGLUT1, there is no report about the VGLUT(s) of the unipolar brush cell (UBC), the second type of glutamatergic interneuron residing in the cerebellar granular layer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14614902", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 759, "text": "Large clusters of labeled nuclei consisting mainly of granule cells and calretinin-positive unipolar brush cells were present in the granular layer, whereas Purkinje cell nuclei were unlabeled, and labeled basket and stellate cell nuclei were scattered in the molecular layer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15940501", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Unipolar brush cells (UBCs) are a class of excitatory interneuron found in the granule cell layer of the vestibulocerebellum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19409228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "TBR2-immunopsitive unipolar brush cells are associated with ectopic zebrin II-immunoreactive Purkinje cell clusters in the cerebellum of scrambler mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21190007", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Glutamate receptor subunits at mossy fiber-unipolar brush cell synapses: light and electron microscopic immunocytochemical study in cerebellar cortex of rat and cat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7673463", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Properties of transmission at a giant glutamatergic synapse in cerebellum: the mossy fiber-unipolar brush cell synapse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7472327", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Metabotropic glutamate receptors are associated with non-synaptic appendages of unipolar brush cells in rat cerebellar cortex and cochlear nuclear complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9923978", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The unipolar brush cells of the rat cerebellar cortex and cochlear nucleus are calretinin-positive: a study by light and electron microscopic immunocytochemistry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7978355", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Cerebellar choline acetyltransferase positive mossy fibres and their granule and unipolar brush cell targets: a model for central cholinergic nicotinic neurotransmission.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9023728", "endSection": "title" }, { "offsetInBeginSection": 749, "offsetInEndSection": 873, "text": "In cerebellum, unipolar brush cells (UBCs) were densely Eps8 immunopositive and granule cells were moderately immunostained.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17223277", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1250, "text": "In the monkey cerebellum, unipolar brush cells, localized in the granular layer, were heavily labeled, whereas Golgi cells were devoid of NG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12655510", "endSection": "abstract" }, { "offsetInBeginSection": 2164, "offsetInEndSection": 2415, "text": "The results indicate that synaptic excitation of unipolar brush cells by mossy fibers will drive a large population of granule cells, and thus will contribute a powerful form of distributed excitation within the basic circuit of the cerebellar cortex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 339, "text": "These neurons, here termed unipolar brush cells, are intermediate in size between granule cells and Golgi cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8300904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Extraordinary synapses of the unipolar brush cell: an electron microscopic study in the rat cerebellum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8059339", "endSection": "title" }, { "offsetInBeginSection": 488, "offsetInEndSection": 728, "text": "Knowledge of the ultrastructure of the unipolar brush cell terminals and of the cellular identity of its postsynaptic targets is required to understand how unipolar brush cells contribute to information processing in the cerebellar circuit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8300904", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Postnatal differentiation of unipolar brush cells and mossy fiber-unipolar brush cell synapses in rat cerebellum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11457596", "endSection": "title" }, { "offsetInBeginSection": 729, "offsetInEndSection": 1005, "text": "To investigate the unipolar brush cell axon and its targets, unipolar brush cells were patch-clamped in fresh parasagittal slices from rat cerebellar vermis with electrodes filled with Lucifer Yellow and Biocytin, and examined by confocal fluorescence and electron microscopy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10891606", "endSection": "abstract" } ] }, { "body": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26727948", "http://www.ncbi.nlm.nih.gov/pubmed/27048880", "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "http://www.ncbi.nlm.nih.gov/pubmed/25182241", "http://www.ncbi.nlm.nih.gov/pubmed/27251074", "http://www.ncbi.nlm.nih.gov/pubmed/24297113", "http://www.ncbi.nlm.nih.gov/pubmed/25773741" ], "ideal_answer": [ "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs", "found conservation of heterozygous k27m mutations in h3f3a (n\u2009=\u20094) or hist1h3b (n\u2009=\u20093) across all primary , contiguous , and metastatic tumor sites in all dipgs . h3k27m ubiquitously-associated mutations involve alterations in tp53 cell-cycle (tp53/ppm1d) or specific growth factor pathways (acvr1/pik3r1) . reconstruction indicates histone 3 (h3) k27m--including h3.2k27m--mutations potentially arise first and are invariably associated with specific , high-fidelity obligate partners throughout the tumour and its spread , from diagnosis to end-stage disease , suggesting mutual need for tumorigenesis. . aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. . ", "We found conservation of heterozygous K27M mutations in H3F3A (n\u00e2\u0080\u0089=\u00e2\u0080\u00894) or HIST1H3B (n\u00e2\u0080\u0089=\u00e2\u0080\u00893) across all primary, contiguous, and metastatic tumor sites in all DIPGs. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1).", "We found conservation of heterozygous K27M mutations in H3F3A (n=4) or HIST1H3B (n=3) across all primary, contiguous, and metastatic tumor sites in all DIPGs. ACVR1 (n=2), PIK3CA (n=2), FGFR1 (n=2), and MET (n=1) were also intra-tumorally conserved. TP53 aberrations (n=3 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). ", "Recurrent mutations within the histone H3 genes H3F3A and HIST1H3B that convert K27 to methionine (H3K27M) and disrupt the global H3K27 methylation landscape and PRC2-dependent silencing, have recently been identified in pediatric high-grade gliomas including Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma multiforme (GBM; Type IV glioma). The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships. TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved.Spatial conservation of prognostically-relevant and therapeutically-targetable somatic mutations in DIPG and mHGG contrasts the significant heterogeneity of driver mutations seen in adult HGG and supports uniform implementation of diagnostic biopsy in DIPG and mHGG to classify molecular risk groups and guide therapeutic strategy. Recently, a subset of these same mutations of ACVR1 have been identified in diffuse intrinsic pontine glioma (DIPG) tumors. Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77\u00a0% of our DIPG cohort. Protein profiling identified 2,305 unique proteins indicating distinct DIPG protein expression patterns compared to other pediatric brain tumors. Two distinct subgroups of DIPG were identified.", "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs ACVR1 (n\u2009=\u20092), PIK3CA (n\u2009=\u20092), FGFR1 (n\u2009=\u20092), and MET (n\u2009=\u20091) were also intra-tumorally conserved TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved.", "Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. Conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) was observed across all primary, contiguous, and metastatic tumor sites in all DIPGs. ACVR1 (n\u2009=\u20092), PIK3CA (n\u2009=\u20092), FGFR1 (n\u2009=\u20092), and MET (n\u2009=\u20091) were also intra-tumorally conserved. TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved.", "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1).", "We found conservation of heterozygous K27M mutations in H3F3A (n=4) or HIST1H3B (n=3) across all primary, contiguous, and metastatic tumor sites in all DIPGs. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). TP53 aberrations (n=3 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. ACVR1 (n=2), PIK3CA (n=2), FGFR1 (n=2), and MET (n=1) were also intra-tumorally conserved. ", "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). " ], "exact_answer": [ [ "K27M in H3F3A" ], [ "HIST1H3B" ] ], "type": "list", "id": "58add1d79ef3c34033000008", "snippets": [ { "offsetInBeginSection": 1101, "offsetInEndSection": 1262, "text": "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26727948", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1361, "text": "ACVR1 (n\u2009=\u20092), PIK3CA (n\u2009=\u20092), FGFR1 (n\u2009=\u20092), and MET (n\u2009=\u20091) were also intra-tumorally conserved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26727948", "endSection": "abstract" }, { "offsetInBeginSection": 1549, "offsetInEndSection": 1691, "text": " TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26727948", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 604, "text": "Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048880", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 755, "text": "These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048880", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 648, "text": "Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78\u00a0% of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36\u00a0% of non-brainstem gliomas carrying either K27M or G34R/V mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "endSection": "abstract" }, { "offsetInBeginSection": 1238, "offsetInEndSection": 1379, "text": "Moreover, in diffuse intrinsic pontine gliomas (DIPG), recurrent somatic mutations of ACVR1 were found in association with HIST1H3B mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182241", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 650, "text": "Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78\u00a0% of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36\u00a0% of non-brainstem gliomas carrying either K27M or G34R/V mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "title" }, { "offsetInBeginSection": 318, "offsetInEndSection": 668, "text": "Recurrent mutations within the histone H3 genes H3F3A and HIST1H3B that convert K27 to methionine (H3K27M) and disrupt the global H3K27 methylation landscape and PRC2-dependent silencing, have recently been identified in pediatric high-grade gliomas including Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma multiforme (GBM; Type IV glioma).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27251074", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1239, "text": "Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77\u00a0% of our DIPG cohort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24297113", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 651, "text": "Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78\u00a0% of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36\u00a0% of non-brainstem gliomas carrying either K27M or G34R/V mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "title" } ] }, { "body": "Does Jarid2 play a role in early embryo development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26190104", "http://www.ncbi.nlm.nih.gov/pubmed/17521633", "http://www.ncbi.nlm.nih.gov/pubmed/24374312", "http://www.ncbi.nlm.nih.gov/pubmed/20075857" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1416528", "o": "JARID2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5139323833330020", "o": "JARID2" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1416528", "o": "http://linkedlifedata.com/resource/umls/label/A20738817" } ], "ideal_answer": [ "Yes. Jarid2 coordinates Nanog expression and PCP/Wnt signaling required for efficient ESC differentiation and early embryo development." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0009790", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047108", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005314", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063146" ], "type": "yesno", "id": "5883781b2305cd7e21000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26190104", "endSection": "title" }, { "offsetInBeginSection": 107, "offsetInEndSection": 1159, "text": "Unlike other PRC2-deficient embryonic stem cells (ESCs), however, Jarid2-deficient ESCs show a severe differentiation block, altered colony morphology, and distinctive patterns of deregulated gene expression. Here, we show that Jarid2(-/-) ESCs express constitutively high levels of Nanog but reduced PCP signaling components Wnt9a, Prickle1, and Fzd2 and lowered \u03b2-catenin activity. Depletion of Wnt9a/Prickle1/Fzd2 from wild-type ESCs or overexpression of Nanog largely phenocopies these cellular defects. Co-culture of Jarid2(-/-) with wild-type ESCs restores variable Nanog expression and \u03b2-catenin activity and can partially rescue the differentiation block of mutant cells. In addition, we show that ESCs lacking Jarid2 or Wnt9a/Prickle1/Fzd2 or overexpressing Nanog induce multiple ICM formation when injected into normal E3.5 blastocysts. These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26190104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26190104", "endSection": "title" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1075, "text": "Consistent with an essential role for PcG proteins in early development, we demonstrate that JARID2 is required for the differentiation of mouse embryonic stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20075857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Jumonij (JMJ)/Jarid2 plays important roles in embryonic development and functions as a transcriptional repressor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17521633", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1293, "text": "Thus, these results demonstrate that JARID2 is essential for the binding of PcG proteins to target genes and, consistent with this, for the proper differentiation of embryonic stem cells and normal development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20075857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "JARID2 is an accessory component of Polycomb repressive complex-2 (PRC2) required for the differentiation of embryonic stem cells (ESCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24374312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26190104", "endSection": "title" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1160, "text": "These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26190104", "endSection": "abstract" } ] }, { "body": "Is PUVA therapy indicated for eczema treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3903677", "http://www.ncbi.nlm.nih.gov/pubmed/23420314", "http://www.ncbi.nlm.nih.gov/pubmed/8088142", "http://www.ncbi.nlm.nih.gov/pubmed/17254029", "http://www.ncbi.nlm.nih.gov/pubmed/708596", "http://www.ncbi.nlm.nih.gov/pubmed/10321515", "http://www.ncbi.nlm.nih.gov/pubmed/8445063", "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "http://www.ncbi.nlm.nih.gov/pubmed/18712324", "http://www.ncbi.nlm.nih.gov/pubmed/15611423", "http://www.ncbi.nlm.nih.gov/pubmed/7662576", "http://www.ncbi.nlm.nih.gov/pubmed/17673386", "http://www.ncbi.nlm.nih.gov/pubmed/9640882", "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "http://www.ncbi.nlm.nih.gov/pubmed/14699368", "http://www.ncbi.nlm.nih.gov/pubmed/22738245", "http://www.ncbi.nlm.nih.gov/pubmed/11499537", "http://www.ncbi.nlm.nih.gov/pubmed/9146535" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0034172", "o": "PUVA Therapy" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0034172", "o": "http://linkedlifedata.com/resource/umls/label/A0444272" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0444272", "o": "PUVA therapy" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1704892", "o": "PUVA therapy" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0034172", "o": "http://linkedlifedata.com/resource/umls/label/A0107279" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0107279", "o": "Psoralen Ultraviolet A Therapy" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0034172", "o": "http://linkedlifedata.com/resource/umls/label/A20221619" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20221619", "o": "Psoralen Ultraviolet A Therapy" } ], "ideal_answer": [ "Yes, PUVA (psoralen plus UVA) therapy is effective for eczema treatment and has relatively few side effects." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004485", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011701" ], "type": "yesno", "id": "58bfe70e02b8c60953000019", "snippets": [ { "offsetInBeginSection": 719, "offsetInEndSection": 960, "text": "With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22738245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Oral vs. bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 148, "text": "Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1290, "text": "Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Treatment of hand eczema is dominated by the administration of topical glucocorticosteriods. If topical treatment fails, the best second-line option is ultraviolet (UV) therapy alone or as combination therapy. UVB and PUVA (psoralen plus UVA) therapy is effective and has relatively few side effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18712324", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 301, "text": "Although local PUVA has been proven to be effective in the treatment of chronic hand eczema, little is known about the efficacy and safety of local narrowband UVB (TL-01) for this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17254029", "endSection": "abstract" }, { "offsetInBeginSection": 1869, "offsetInEndSection": 2015, "text": "Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17254029", "endSection": "abstract" }, { "offsetInBeginSection": 1631, "offsetInEndSection": 1859, "text": "Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Treatment of chronic palmoplantar eczema with local bath-PUVA therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7662576", "endSection": "title" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1076, "text": "These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7662576", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 458, "text": "In order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Does smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "title" }, { "offsetInBeginSection": 158, "offsetInEndSection": 210, "text": "PUVA therapy caused acute aggravation of the eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8088142", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1290, "text": "Hyperkeratotic eczema cleared significantly better with oral than with bath PUVA (P=0.03).CONCLUSION: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND: Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1082, "text": "These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7662576", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1026, "text": "Vitiligo (60.9%) was the commonest skin disorder treated with PUVA, followed by psoriasis (20.9%), endogenous eczema (11.3%), mycosis fungoides (3.5%), lichen amyloidosis (2.6%) and prurigo nodularis (0.9%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11499537", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 75, "text": "bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "A 36-year-old female patient was treated with PUVA for dyshidrotic eczema that had not shown sufficient response to topical therapy over the previous months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8088142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BACKGROUND: Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1179, "text": "One patient with hand eczema consistently had detectable 8-MOP levels 1 hour after topical PUVA treatments.CONCLUSION: This report indicates that there is minimal, if any, systemic absorption of 8-MOP after topical PUVA treatment of patients with palmoplantar psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8445063", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1963, "text": "In the narrowband UVB-treated side, the tolerance of all the patients to the treatment was good all patients well-tolerated the treatment with the exception of mild xerosis that responded to topical emollients.Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17254029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 1648, "offsetInEndSection": 1875, "text": "Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 710, "text": "However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1504, "text": "No phototoxic reactions were observed.Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Treatment of chronic palmoplantar eczema with local bath-PUVA therapy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 1642, "offsetInEndSection": 1870, "text": "Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 566, "text": "OBJECTIVE: Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1563, "text": "CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Topical PUVA therapy for chronic hand eczema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9640882", "endSection": "title" }, { "offsetInBeginSection": 253, "offsetInEndSection": 711, "text": "However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1505, "text": "No phototoxic reactions were observed.Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 1648, "offsetInEndSection": 1876, "text": "Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 250, "text": "However, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1964, "text": "In the narrowband UVB-treated side, the tolerance of all the patients to the treatment was good all patients well-tolerated the treatment with the exception of mild xerosis that responded to topical emollients.Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17254029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Comparison of localized high-dose UVA1 irradiation versus topical cream psoralen-UVA for treatment of chronic vesicular dyshidrotic eczema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14699368", "endSection": "title" }, { "offsetInBeginSection": 1374, "offsetInEndSection": 1558, "text": "No phototoxic reactions were observed.CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 1083, "text": "These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7662576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Treatment of chronic palmoplantar eczema with local bath-PUVA therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "title" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1248, "text": "Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19292787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Does smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "title" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1509, "text": "Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 356, "text": "However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7662576", "endSection": "title" }, { "offsetInBeginSection": 1642, "offsetInEndSection": 1871, "text": "Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721861", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 445, "text": "In order to investigate the effectiveness of topical PUVA-bath therapy (PUVA-soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque-type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10321515", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 542, "text": "Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9146535", "endSection": "abstract" } ] }, { "body": "What is DECKO?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26493208" ], "ideal_answer": [ "DECKO (Double Excision CRISPR Knockout) is a dual CRISPR tool, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to CRISPR knockout studies of non-coding genomic elements, including long non-coding RNAs." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064113" ], "type": "summary", "id": "58837ba62305cd7e21000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "DECKO: Single-oligo, dual-CRISPR deletion of genomic elements including long non-coding RNAs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "title" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1443, "text": "We present a dual CRISPR tool, DECKO, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to CRISPR knockout studies of non-coding genomic elements, including long non-coding RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 559, "text": " We present a vector system adapted for this purpose called DECKO (Double Excision CRISPR Knockout), which applies a simple two-step cloning to generate lentiviral vectors expressing two guide RNAs (gRNAs) simultaneously. The key feature of DECKO is its use of a single 165 bp starting oligonucleotide carrying the variable sequences of both gRNAs, making it fully scalable from single-locus studies to complex library cloning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "DECKO: Single-oligo, dual-CRISPR deletion of genomic elements including long non-coding RNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "title" }, { "offsetInBeginSection": 120, "offsetInEndSection": 340, "text": "We present a vector system adapted for this purpose called DECKO (Double Excision CRISPR Knockout), which applies a simple two-step cloning to generate lentiviral vectors expressing two guide RNAs (gRNAs) simultaneously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 545, "text": "The key feature of DECKO is its use of a single 165 bp starting oligonucleotide carrying the variable sequences of both gRNAs, making it fully scalable from single-locus studies to complex library cloning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 340, "text": "We present a vector system adapted for this purpose called DECKO (Double Excision CRISPR Knockout), which applies a simple two-step cloning to generate lentiviral vectors expressing two guide RNAs (gRNAs) simultaneously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 748, "text": "The key feature of DECKO is its use of a single 165 bp starting oligonucleotide carrying the variable sequences of both gRNAs, making it fully scalable from single-locus studies to complex library cloning.We apply DECKO to deleting the promoters of one protein-coding gene and two oncogenic lncRNAs, UCA1 and the highly-expressed MALAT1, focus of many previous studies employing RNA interference approaches", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1408, "text": "These clones have reductions in steady-state MALAT1 RNA levels of up to 98 % and display reduced proliferation rates.We present a dual CRISPR tool, DECKO, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to CRISPR knockout studies of non-coding genomic elements, including long non-coding RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 341, "text": "We present a vector system adapted for this purpose called DECKO (Double Excision CRISPR Knockout), which applies a simple two-step cloning to generate lentiviral vectors expressing two guide RNAs (gRNAs) simultaneously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 749, "text": "The key feature of DECKO is its use of a single 165 bp starting oligonucleotide carrying the variable sequences of both gRNAs, making it fully scalable from single-locus studies to complex library cloning.We apply DECKO to deleting the promoters of one protein-coding gene and two oncogenic lncRNAs, UCA1 and the highly-expressed MALAT1, focus of many previous studies employing RNA interference approaches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1409, "text": "These clones have reductions in steady-state MALAT1 RNA levels of up to 98 % and display reduced proliferation rates.We present a dual CRISPR tool, DECKO, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to CRISPR knockout studies of non-coding genomic elements, including long non-coding RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "DECKO: Single-oligo, dual-CRISPR deletion of genomic elements including long non-coding RNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "title" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1412, "text": "We present a dual CRISPR tool, DECKO, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to CRISPR knockout studies of non-coding genomic elements, including long non-coding RNAs..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493208", "endSection": "abstract" } ] }, { "body": "List genes associated with hypolipidemia.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22247256", "http://www.ncbi.nlm.nih.gov/pubmed/26546829", "http://www.ncbi.nlm.nih.gov/pubmed/24751931", "http://www.ncbi.nlm.nih.gov/pubmed/22062970" ], "ideal_answer": [ "PCSK9\nAPOB \nANGPTL3\nANGPTL4\nMTP" ], "exact_answer": [ [ "PCSK9" ], [ "APOB" ], [ "ANGPTL3" ], [ "ANGPTL4" ], [ "MTP" ] ], "type": "list", "id": "58dfd83a6fddd3e83e000003", "snippets": [ { "offsetInBeginSection": 622, "offsetInEndSection": 788, "text": " Conversely familial hypobetalipoproteinemia is caused by inactivation of the PCSK9 gene which increases the number of LDL receptors and decreases plasma cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26546829", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 985, "text": "Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can further cause low levels of apoB containing lipoproteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26546829", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 329, "text": "Several mutations in the apoB, proprotein convertase subtilisin/kexin type 9 (PCSK9), and MTP genes result in low or absent levels of apoB and LDL-cholesterol in plasma, which cause familial hypobetalipoproteinemia and abetalipoproteinemia. Mutations in the ANGPTL3 gene cause familial combined hypolipidemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24751931", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 222, "text": "Mutations of the ANGPTL3 gene have been associated with a novel form of primary hypobetalipoproteinemia, the combined hypolipidemia (cHLP), characterized by low total cholesterol and low HDL-cholesterol levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247256", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1437, "text": "These results demonstrated that in a cohort of subjects with severe primary hypobetalipoproteinemia the prevalence of ANGPTL3 gene mutations responsible for a combined hypolipidemia phenotype is about 10%, whereas mutations of APOB gene are absent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247256", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 354, "text": "Angptl3 knockout mice have marked hypolipidemia, and heterozygous carriers of ANGPLT3, loss-of-function mutations were found among individuals in the lowest quartile of plasma triglycerides in population studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22062970", "endSection": "abstract" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 2022, "text": "Complete ANGPTL3 deficiency caused by loss-of-function mutations of ANGPTL3 is associated with a recessive hypolipidemia characterized by a reduction of apolipoprotein B and apolipoprotein A-I-containing lipoproteins, changes in subclasses of high-density lipoprotein, and reduced cholesterol efflux potential of serum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22062970", "endSection": "abstract" } ] }, { "body": "What is the enzymatic activity of PARL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17938163", "http://www.ncbi.nlm.nih.gov/pubmed/21415861", "http://www.ncbi.nlm.nih.gov/pubmed/21355049", "http://www.ncbi.nlm.nih.gov/pubmed/19859837" ], "ideal_answer": [ "the mitochondrial protease presenilin-associated rhomboid-like (PARL). Rhomboids are a recently discovered family of widely distributed intramembrane serine proteases." ], "exact_answer": [ "PARL are serine proteases" ], "type": "factoid", "id": "58dfe6b56fddd3e83e000004", "snippets": [ { "offsetInBeginSection": 743, "offsetInEndSection": 970, "text": "Here we demonstrate that the mitochondrial protease presenilin-associated rhomboid-like (PARL) can affect the proteolytic processing of PINK1 and that normal PINK1 localization and stability requires PARL's catalytic activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21355049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "The mitochondrial rhomboid protease Parl governs apoptosis, morphology, metabolism and might be implicated in Parkinson's disease, but the structural basis of its activity and complex regulation remain unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415861", "endSection": "abstract" }, { "offsetInBeginSection": 43, "offsetInEndSection": 248, "text": ". In this study, we evaluated the mRNA levels of presenilins-associated rhomboid-like protein (PARL) and mitochondrial content and enzyme activity from skeletal muscle isolated from insulin-resistant rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19859837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Rhomboids are a recently discovered family of widely distributed intramembrane serine proteases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17938163", "endSection": "abstract" } ] }, { "body": "Do brown fat cells produce heat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23834768", "http://www.ncbi.nlm.nih.gov/pubmed/26910308", "http://www.ncbi.nlm.nih.gov/pubmed/22796012", "http://www.ncbi.nlm.nih.gov/pubmed/21196229", "http://www.ncbi.nlm.nih.gov/pubmed/23818608", "http://www.ncbi.nlm.nih.gov/pubmed/6148836", "http://www.ncbi.nlm.nih.gov/pubmed/3083882", "http://www.ncbi.nlm.nih.gov/pubmed/26496384", "http://www.ncbi.nlm.nih.gov/pubmed/26322018", "http://www.ncbi.nlm.nih.gov/pubmed/15058310", "http://www.ncbi.nlm.nih.gov/pubmed/6819159", "http://www.ncbi.nlm.nih.gov/pubmed/21982742", "http://www.ncbi.nlm.nih.gov/pubmed/26912151", "http://www.ncbi.nlm.nih.gov/pubmed/27528872", "http://www.ncbi.nlm.nih.gov/pubmed/8042786", "http://www.ncbi.nlm.nih.gov/pubmed/25642708", "http://www.ncbi.nlm.nih.gov/pubmed/962510", "http://www.ncbi.nlm.nih.gov/pubmed/27528697", "http://www.ncbi.nlm.nih.gov/pubmed/27552974", "http://www.ncbi.nlm.nih.gov/pubmed/1550210", "http://www.ncbi.nlm.nih.gov/pubmed/25068090", "http://www.ncbi.nlm.nih.gov/pubmed/2039657", "http://www.ncbi.nlm.nih.gov/pubmed/21123942", "http://www.ncbi.nlm.nih.gov/pubmed/9277366", "http://www.ncbi.nlm.nih.gov/pubmed/24129212", "http://www.ncbi.nlm.nih.gov/pubmed/5262992", "http://www.ncbi.nlm.nih.gov/pubmed/24046370", "http://www.ncbi.nlm.nih.gov/pubmed/24567786", "http://www.ncbi.nlm.nih.gov/pubmed/6315457", "http://www.ncbi.nlm.nih.gov/pubmed/541897", "http://www.ncbi.nlm.nih.gov/pubmed/25466254", "http://www.ncbi.nlm.nih.gov/pubmed/16594742", "http://www.ncbi.nlm.nih.gov/pubmed/26749900", "http://www.ncbi.nlm.nih.gov/pubmed/22654830", "http://www.ncbi.nlm.nih.gov/pubmed/19641492" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0018837", "o": "Heat" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0018837", "o": "http://linkedlifedata.com/resource/umls/label/A0066521" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0066521", "o": "Heat" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0018837", "o": "http://linkedlifedata.com/resource/umls/label/A18591807" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18591807", "o": "heat" } ], "ideal_answer": [ "Yes, brown fat cells produce heat." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002001", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052437", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006359", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005223" ], "type": "yesno", "id": "58ca906a02b8c6095300002e", "snippets": [ { "offsetInBeginSection": 271, "offsetInEndSection": 512, "text": "WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24567786", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 288, "text": "Because brown adipose\u00a0tissue (BAT) dissipates energy in the form of heat, increasing energy expenditure by augmenting BAT-mediated thermogenesis may represent an approach to counter obesity and its complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25466254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1. This nonshivering thermogenesis is crucial for mammals as a defense against cold and obesity/diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818608", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 245, "text": "Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22654830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 36, "text": "Brown fat biology and thermogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196229", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Brown fat (brown adipose tissue, BAT) primary function is to produce heat. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196229", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 353, "text": "Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962510", "endSection": "abstract" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1487, "text": "Calorimetric measurements from cell suspensions showed that ATP increased basal heat production of isolated brown fat cells by approximately 40% but had no effect on the greater than fivefold increase in heat production seen with maximal adrenergic stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9277366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Brown adipocytes oxidize fatty acids to produce heat in response to cold or to excessive energy intake; stimulation of brown fat development and function may thus counteract obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21982742", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1285, "text": "The occurrence of Types 1 and/or 6 cells that has been revealed in 65 out of the total 180 samples (36%), suggests that the oxidation of fat for the thermogenesis proceeds in the brown fat tissue and that brown fat cells partially undergo fat depletion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962510", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 354, "text": "Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962510", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 333, "text": "In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by \u03b2-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26322018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26496384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor \u03b11", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24046370", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Brown fat and vascular heat dissipation: The new cautionary tail", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25068090", "endSection": "title" }, { "offsetInBeginSection": 255, "offsetInEndSection": 458, "text": "Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21123942", "endSection": "abstract" }, { "offsetInBeginSection": 1764, "offsetInEndSection": 1902, "text": "In the same manner, marked ability to produce a considerable amount of heat was evidenced in brown fat tissue of children and teenagers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962510", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 355, "text": "Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962510", "endSection": "abstract" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1739, "text": "It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8042786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Parallel measurements of heat production and thermogenin content in brown fat cells during cold acclimation of rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3083882", "endSection": "title" }, { "offsetInBeginSection": 39, "offsetInEndSection": 287, "text": "The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27528872", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 334, "text": "In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by \u03b2-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26322018", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 245, "text": "White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23834768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The main function of brown adipose tissue (BAT) is to produce heat in response to cold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6148836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Brown adipocytes oxidize fatty acids to produce heat in response to cold or caloric overfeeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Brown fat (brown adipose tissue, BAT) primary function is to produce heat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196229", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Adipose tissue plays an active role in energy balance because it is not only a lipid storing and mobilizing tissue but consists of functionally specialized tissues able to produce heat (in brown adipose tissue) and to produce or release a vast number of so called adipokines or adipocytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15058310", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, plays an important role in the regulation of energy balance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25642708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19641492", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1430, "text": "In the present study, the thermogenesis of human brown fat tissue was suggested chiefly with regard to the occurrence of Types 1 and/or 6 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962510", "endSection": "abstract" }, { "offsetInBeginSection": 1764, "offsetInEndSection": 1901, "text": "In the same manner, marked ability to produce a considerable amount of heat was evidenced in brown fat tissue of children and teenagers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/962510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26749900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552974", "endSection": "abstract" }, { "offsetInBeginSection": 2005, "offsetInEndSection": 2203, "text": "In human perirenal brown fat tissue, darkly stained fat-depleted cells (D) occupy, with other cell types (CR, CR'), an important part in the reversible heat production cycle of the brown fat tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2039657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Brown fat is a specialized fat depot that can increase energy expenditure and produce heat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26912151", "endSection": "abstract" } ] }, { "body": "What is a mimotope vaccine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15634921", "http://www.ncbi.nlm.nih.gov/pubmed/16634806", "http://www.ncbi.nlm.nih.gov/pubmed/19344285", "http://www.ncbi.nlm.nih.gov/pubmed/16814270", "http://www.ncbi.nlm.nih.gov/pubmed/19846865", "http://www.ncbi.nlm.nih.gov/pubmed/19111573", "http://www.ncbi.nlm.nih.gov/pubmed/7534789", "http://www.ncbi.nlm.nih.gov/pubmed/24106273", "http://www.ncbi.nlm.nih.gov/pubmed/19695868", "http://www.ncbi.nlm.nih.gov/pubmed/23161490", "http://www.ncbi.nlm.nih.gov/pubmed/19088033", "http://www.ncbi.nlm.nih.gov/pubmed/27622022", "http://www.ncbi.nlm.nih.gov/pubmed/17445956", "http://www.ncbi.nlm.nih.gov/pubmed/25990849", "http://www.ncbi.nlm.nih.gov/pubmed/22936035", "http://www.ncbi.nlm.nih.gov/pubmed/11122460", "http://www.ncbi.nlm.nih.gov/pubmed/21919618", "http://www.ncbi.nlm.nih.gov/pubmed/17597331", "http://www.ncbi.nlm.nih.gov/pubmed/20493257", "http://www.ncbi.nlm.nih.gov/pubmed/20827761", "http://www.ncbi.nlm.nih.gov/pubmed/25379726", "http://www.ncbi.nlm.nih.gov/pubmed/16685414" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/11094", "o": "http://linkedlifedata.com/resource/rxnorm/label/354401" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/354401", "o": "Vaccines" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/11094", "o": "http://linkedlifedata.com/resource/rxnorm/label/3254401" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3254401", "o": "Vaccines" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0042210", "o": "Vaccine" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0042210", "o": "http://linkedlifedata.com/resource/umls/label/A11798658" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11798658", "o": "Vaccine" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/11094", "o": "http://linkedlifedata.com/resource/rxnorm/label/354410" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/354410", "o": "Vaccine" } ], "ideal_answer": [ "A mimotope vaccine contains peptide mimics of specific antigen epitopes, which alter the antigen presentation and/or T cell activation to increase the expansion of tumor-specific T cells and are able to induce polyclonal antibodies response." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016233", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064166", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014612" ], "type": "summary", "id": "58d388958acda34529000006", "snippets": [ { "offsetInBeginSection": 1704, "offsetInEndSection": 1980, "text": "These data are proof of principle that by performing affinity selection on neutralizing antibodies, our VLP technology can identify peptide mimics of non-linear epitopes and that these mimotope based VLP vaccines provide protection against pathogens in relevant animal models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25379726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 657, "text": "A major hurdle in vaccine development is the difficulty in identifying relevant target epitopes and then presenting them to the immune system in a context that mimics their native conformation. We have engineered novel virus-like-particle (VLP) technology that is able to display complex libraries of random peptide sequences on a surface-exposed loop in the coat protein without disruption of protein folding or VLP assembly. This technology allows us to use the same VLP particle for both affinity selection and immunization, integrating the power of epitope discovery and epitope mimicry of traditional phage display with the high immunogenicity of VLPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25379726", "endSection": "abstract" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1630, "text": "Our data suggest that the improved tumor immunity results from the expansion of mimotope-elicited tumor-specific T cells that have increased avidity for the tumor antigen. The enhanced T cells are phenotypically distinct and enriched for T-cell receptors previously correlated with improved antitumor immunity. These results suggest that incorporation of native antigen into clinical mimotope vaccine regimens may improve the efficacy of antitumor T-cell responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161490", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 911, "text": "One strategy for overcoming these mechanisms is vaccination with mimotopes, or peptide mimics of tumor antigens, which alter the antigen presentation and/or T cell activation to increase the expansion of tumor-specific T cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22936035", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 296, "text": "The high molecular weight melanoma-associated antigen (HMW-MAA) is an attractive target for immunotherapy of malignant melanoma. We have recently generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to induce anti-HMW-MAA antibodies with antitumor activity in vitro. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19088033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Peptide mimics of a conformational epitope that is recognized by a mAb with antitumor activity are promising candidates for formulations of anticancer vaccines. These mimotope vaccines are able to induce a polyclonal Ab response focused to the determinant of the mAb. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15634921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Carbohydrate mimetic peptides of tumor associated carbohydrate antigens (TACA) are T-cell-dependent antigens and, therefore, immunization with these surrogates is predicted to overcome the low immunogenicity of carbohydrate antigens. Consistent with this hypothesis, we show that among the potential immune cells involved, peptide immunization led to an increase in T-cell populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16685414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 802, "text": "To explore the mimotope vaccine approach against infectious bursal disease virus (IBDV), five IBDV-specific monoclonal antibodies (mAbs) were prepared and their binding peptides were screened against a phage-displayed 12-mer peptide library. After three rounds of biopanning, 12 phages were selected for each mAbs and their specificity to IBDV was verified by sandwich and competitive inhibition ELISAs. Seven phages per mAb were sequenced and their amino acid sequences were deduced. The five representative sequences of mimotopes corresponding mAbs were determined. An artificial gene, designated 5epis (5 epitopes) and consisting of the five mimotopes arranged in tandem (F1-F7-B34-2B1-2G8) with four GGGS spacers, was chemically synthesized and cloned into a prokaryotic expression plasmid pET28b. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17445956", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 862, "text": "The mimotope vaccine was then generated by coupling the most suitable candidate mimotope to tetanus toxoid as an immunogenic carrier.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15634921", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 973, "text": "We hypothesized that boosting the mimotope vaccine with the native tumor antigen would focus the T-cell response elicited by the mimotope toward high affinity, tumor-specific T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161490", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 672, "text": "Following the mice immunization, phage-based mimotope vaccine induced humoral immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25990849", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 796, "text": "In this article we focus on cancer vaccines for antibody production, in particular mimotope vaccines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21919618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Vaccines that incorporate peptide mimics of tumor antigens, or mimotope vaccines, are commonly used in cancer immunotherapy and function by eliciting increased numbers of T cells that cross-react with the native tumor antigen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106273", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 978, "text": "We hypothesized that boosting the mimotope vaccine with the native tumor antigen would focus the T-cell response elicited by the mimotope toward high affinity, tumor-specific T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Augmenting antitumor T-cell responses to mimotope vaccination by boosting with native tumor antigens.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23161490", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Induction of protective immune responses against NXS2 neuroblastoma challenge in mice by immunotherapy with GD2 mimotope vaccine and IL-15 and IL-21 gene delivery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17597331", "endSection": "title" }, { "offsetInBeginSection": 161, "offsetInEndSection": 267, "text": "These mimotope vaccines are able to induce a polyclonal Ab response focused to the determinant of the mAb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15634921", "endSection": "abstract" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1628, "text": "We therefore suggest that mimotope gene vaccines are potential candidates for epitope-specific immunotherapy of type I allergy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19111573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Conformational B-cell epitopes on the HCV E2 protein recognized by human antibodies were characterized by the use of a peptide mimotope named K1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20827761", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 677, "text": "Following the mice immunization, phage-based mimotope vaccine induced humoral immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25990849", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 801, "text": "In this article we focus on cancer vaccines for antibody production, in particular mimotope vaccines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21919618", "endSection": "abstract" } ] }, { "body": "Describe clinical manifestation of the Mal de debarquement syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25570942", "http://www.ncbi.nlm.nih.gov/pubmed/25076935", "http://www.ncbi.nlm.nih.gov/pubmed/25809585", "http://www.ncbi.nlm.nih.gov/pubmed/23219828", "http://www.ncbi.nlm.nih.gov/pubmed/26559820", "http://www.ncbi.nlm.nih.gov/pubmed/26252893", "http://www.ncbi.nlm.nih.gov/pubmed/17046477", "http://www.ncbi.nlm.nih.gov/pubmed/27730651", "http://www.ncbi.nlm.nih.gov/pubmed/23202153", "http://www.ncbi.nlm.nih.gov/pubmed/25726862", "http://www.ncbi.nlm.nih.gov/pubmed/23209584", "http://www.ncbi.nlm.nih.gov/pubmed/22231864", "http://www.ncbi.nlm.nih.gov/pubmed/8336953", "http://www.ncbi.nlm.nih.gov/pubmed/23091536", "http://www.ncbi.nlm.nih.gov/pubmed/3631419", "http://www.ncbi.nlm.nih.gov/pubmed/24594496", "http://www.ncbi.nlm.nih.gov/pubmed/26346344", "http://www.ncbi.nlm.nih.gov/pubmed/25331814" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1608983", "o": "http://linkedlifedata.com/resource/umls/label/A18471215" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18471215", "o": "Mal de debarquement syndrome" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1608983", "o": "Mal de debarquement" } ], "ideal_answer": [ "Mal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea voyage, and involves the perception of low-frequency rocking that can last for months or years." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "summary", "id": "588f9b7eed9bbee70d000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 409, "text": "Mal de debarquement (MdD) is a subjective perception of self-motion after exposure to passive motion, in most cases sea travel, hence the name. Mal de debarquement occurs quite frequently in otherwise healthy individuals for a short period of time (several hours). However, in some people symptoms remain for a longer period of time or even persist and this is then called mal de debarquement syndrome (MdDS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26559820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "OBJECTIVE: Mal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27730651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Mal de debarquement syndrome (MdDS) is a rare and poorly understood condition of perceived continual motion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25809585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "BACKGROUND: Mal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea voyage, and involves the perception of low-frequency rocking that can last for months or years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252893", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 335, "text": "It is characterized by abnormal sensation of motion/balance reported after travel by air, land, and sea; being reexposed to motion/activity relieves it. Symptoms may last from minutes to years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Persistent mal de debarquement syndrome: a motion-induced subjective disorder of balance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3631419", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Mal de debarquement syndrome (MdDS) is a disorder of phantom perception of self-motion of unknown cause. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22231864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Mal de debarquement (MDD) is a common, benign, and self-limited syndrome suffered by many people after disembarkation from an oceangoing vessel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Persistent mal de debarquement syndrome: a motion-induced subjective disorder of balance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3631419", "endSection": "title" } ] }, { "body": "Is Melioidosis caused by the bacterium\u00a0Burkholderia pseudomallei?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24603493", "http://www.ncbi.nlm.nih.gov/pubmed/22624016", "http://www.ncbi.nlm.nih.gov/pubmed/26542622", "http://www.ncbi.nlm.nih.gov/pubmed/26495852", "http://www.ncbi.nlm.nih.gov/pubmed/19538822", "http://www.ncbi.nlm.nih.gov/pubmed/27303718", "http://www.ncbi.nlm.nih.gov/pubmed/22176696", "http://www.ncbi.nlm.nih.gov/pubmed/17582188", "http://www.ncbi.nlm.nih.gov/pubmed/25653950", "http://www.ncbi.nlm.nih.gov/pubmed/12139670", "http://www.ncbi.nlm.nih.gov/pubmed/19156200", "http://www.ncbi.nlm.nih.gov/pubmed/26935879", "http://www.ncbi.nlm.nih.gov/pubmed/27427979", "http://www.ncbi.nlm.nih.gov/pubmed/25803046", "http://www.ncbi.nlm.nih.gov/pubmed/26710411", "http://www.ncbi.nlm.nih.gov/pubmed/9753000", "http://www.ncbi.nlm.nih.gov/pubmed/24145517", "http://www.ncbi.nlm.nih.gov/pubmed/15191392", "http://www.ncbi.nlm.nih.gov/pubmed/12803798", "http://www.ncbi.nlm.nih.gov/pubmed/27694236", "http://www.ncbi.nlm.nih.gov/pubmed/17563759", "http://www.ncbi.nlm.nih.gov/pubmed/18691413", "http://www.ncbi.nlm.nih.gov/pubmed/22473609", "http://www.ncbi.nlm.nih.gov/pubmed/24736221", "http://www.ncbi.nlm.nih.gov/pubmed/24067292", "http://www.ncbi.nlm.nih.gov/pubmed/27219859", "http://www.ncbi.nlm.nih.gov/pubmed/22442327", "http://www.ncbi.nlm.nih.gov/pubmed/11495298", "http://www.ncbi.nlm.nih.gov/pubmed/15380526", "http://www.ncbi.nlm.nih.gov/pubmed/14604083", "http://www.ncbi.nlm.nih.gov/pubmed/22564963", "http://www.ncbi.nlm.nih.gov/pubmed/20142364", "http://www.ncbi.nlm.nih.gov/pubmed/25689538", "http://www.ncbi.nlm.nih.gov/pubmed/24065633", "http://www.ncbi.nlm.nih.gov/pubmed/17676990", "http://www.ncbi.nlm.nih.gov/pubmed/24962103", "http://www.ncbi.nlm.nih.gov/pubmed/17062053", "http://www.ncbi.nlm.nih.gov/pubmed/20169062", "http://www.ncbi.nlm.nih.gov/pubmed/19276877", "http://www.ncbi.nlm.nih.gov/pubmed/18855560", "http://www.ncbi.nlm.nih.gov/pubmed/26311902", "http://www.ncbi.nlm.nih.gov/pubmed/26607593", "http://www.ncbi.nlm.nih.gov/pubmed/24392083", "http://www.ncbi.nlm.nih.gov/pubmed/27472421", "http://www.ncbi.nlm.nih.gov/pubmed/26526925", "http://www.ncbi.nlm.nih.gov/pubmed/20532233", "http://www.ncbi.nlm.nih.gov/pubmed/19679240", "http://www.ncbi.nlm.nih.gov/pubmed/25943405", "http://www.ncbi.nlm.nih.gov/pubmed/25442759" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0025229", "o": "Melioidosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0025229", "o": "http://linkedlifedata.com/resource/umls/label/A0432241" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0432241", "o": "MELIOIDOSIS" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0025229", "o": "http://linkedlifedata.com/resource/umls/label/A0084485" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0084485", "o": "Melioidosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/1025638", "o": "http://linkedlifedata.com/resource/rxnorm/label/3197303" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3197303", "o": "Melioidosis" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/semanticnetwork/id/T007", "o": "Bacterium" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0004611", "o": "http://linkedlifedata.com/resource/umls/label/A7567988" } ], "ideal_answer": [ "Burkholderia pseudomallei is the causative agent of melioidosis" ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019121", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008554", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016957" ], "type": "yesno", "id": "58caf88c02b8c60953000031", "snippets": [ { "offsetInBeginSection": 222, "offsetInEndSection": 284, "text": "Burkholderia pseudomallei, the causative agent of melioidosis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26935879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "What drives the occurrence of the melioidosis bacterium Burkholderia pseudomallei in domestic gardens?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25803046", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Landscape changes influence the occurrence of the melioidosis bacterium Burkholderia pseudomallei in soil in northern Australia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156200", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Out of the ground: aerial and exotic habitats of the melioidosis bacterium Burkholderia pseudomallei in grasses in Australia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22176696", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Melioidosis, caused by the gram-negative bacterium Burkholderia pseudomallei, is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27219859", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Melioidosis is a suppurative chronic infection caused by a gramnegative bacterium, Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17582188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Melioidosis is an infection caused by the gram-negative bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17062053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Melioidosis is an infectious disease caused by a saprophytic bacterium, Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12803798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Melioidosis is an infectious disease caused by the Gram-negative bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19679240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Melioidosis is a pyogenic infection with high mortality caused by the bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24067292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Melioidosis is a tropical infectious disease caused by the gram-negative bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14604083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15380526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Melioidosis is a rare tropical disease caused by infection with the bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12139670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The mechanisms involved in the pathogenesis of melioidosis, caused by the intracellular bacterium Burkholderia pseudomallei, are unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9753000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Melioidosis is an emerging tropical infection caused by the intracellular bacterium Burkholderia pseudomallei, and is associated with high mortality rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15191392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26495852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Melioidosis, an infection caused by the gram-negative bacterium Burkholderia pseudomallei, is an important cause of pneumonia, skin infection, sepsis, and death in Southeast Asia and Australia, but is exceedingly rare in North America", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25943405", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 391, "text": "The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Melioidosis, a lethal tropical infection that is endemic in southeast Asia and northern Australia, is caused by the saprophytic Gram-negative bacterium Burkholderia pseudomallei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18691413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Melioidosis is an emerging infectious disease caused by the soil bacterium Burkholderia pseudomallei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22442327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Melioidosis is a tropical disease of high mortality caused by the environmental bacterium, Burkholderia pseudomallei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26526925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26542622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Melioidosis is a life-threatening infection caused by the Gram-negative bacterium Burkholderia pseudomallei, mainly found in Southeast Asia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25689538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a dreadful disease common in South-East Asia and Northern Australia and is characterized by chronic suppurative lesions and pneumonia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24962103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Melioidosis is caused by the environmental bacterium Burkholderia pseudomallei and can present with severe sepsis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Melioidosis is an emerging infectious disease of humans and animals in the tropics caused by the soil bacterium Burkholderia pseudomallei. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22176696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Melioidosis, infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is a common cause of sepsis in northeast Thailand. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Melioidosis is a potentially fatal disease caused by the bacterium, Burkholderia pseudomallei. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17563759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND: The soil-dwelling saprophyte bacterium Burkholderia pseudomallei is the cause of melioidosis, a severe disease of humans and animals in southeast Asia and northern Australia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Melioidosis is an endemic disease caused by the bacterium Burkholderia pseudomallei. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603493", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 424, "text": "Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17676990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Melioidosis, infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is a common cause of sepsis in northeast Thailand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24392083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Melioidosis is a clinically diverse disease caused by the facultative intracellular Gram-negative bacterium, Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Melioidosis is caused by the environmental bacterium Burkholderia pseudomallei and can present with severe sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25442759", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 411, "text": "Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17676990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Melioidosis, a lethal tropical infection that is endemic in southeast Asia and northern Australia, is caused by the saprophytic Gram-negative bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18691413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26311902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Melioidosis, an often fatal infectious disease in Northeast Thailand, is caused by skin inoculation, inhalation or ingestion of the environmental bacterium, Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27472421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Melioidosis is an infection caused by Gram-negative bacterium, Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26710411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a dreadful disease common in South-East Asia and Northern Australia and is characterized by chronic suppurative lesions and pneumonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24962103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Largely due to its recognition as a biological threat agent, current knowledge on melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, has increased tremendously over the last years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19276877", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Melioidosis is an endemic disease caused by the bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22473609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Melioidosis is a potentially fatal disease caused by the bacterium, Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17563759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Melioidosis is a disease of humans and animals that is caused by the saprophytic bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26607593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Melioidosis is an emerging infectious disease of humans and animals in the tropics caused by the soil bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22176696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The soil-dwelling saprophyte bacterium Burkholderia pseudomallei is the cause of melioidosis, a severe disease of humans and animals in southeast Asia and northern Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19156200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Melioidosis is an often fatal infectious disease affecting humans and animals in tropical regions and is caused by the saprophytic environmental bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25803046", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 352, "text": "We have recently shown that during melioidosis, a severe infection caused by the gram-negative bacterium Burkholderia pseudomallei, TLR2 but not TLR4 impacts the immune response of the intact host in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18855560", "endSection": "abstract" }, { "offsetInBeginSection": 1767, "offsetInEndSection": 1924, "text": "It is caused by the bacterium Burkholderia pseudomallei, which can infect many organs of the body, including the brain, and results in neurological symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24736221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Melioidosis is a frequent cause of severe sepsis in Southeast Asia caused by the gram-negative bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22564963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "What drives the occurrence of the melioidosis bacterium Burkholderia pseudomallei in domestic gardens?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25803046", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The Gram-negative bacterium Burkholderia pseudomallei is the causative agent of melioidosi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24065633", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 175, "text": "The environmental bacterium Burkholderia pseudomallei causes the infectious disease melioidosis with a high case-fatality rate in tropical and subtropical regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27427979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Burkholderia pseudomallei is a soil-dwelling bacterium and the cause of melioidosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27694236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Melioidosis, an infectious disease caused by the Gram-negative bacterium Burkholderia pseudomallei,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19538822", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 144, "text": "Melioidosis is a frequently fatal infectious disease caused by the soil dwelling Gram-negative bacterium Burkholderia pseudomallei. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20532233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Burkholderia pseudomallei, an environmental bacterium that causes the deadly disease melioidosis, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27303718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Melioidosis is an important public health problem in Southeast Asia and Northern Australia. This disease is caused by the gram-negative bacilli, Burkholderia pseudomallei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11495298", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 301, "text": "Melioidosis, caused by Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast-Asi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20169062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24145517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Melioidosis is a disease of humans caused by opportunistic infection with the soil and water bacterium Burkholderia pseudomallei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22624016", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of verubecestat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27933948", "http://www.ncbi.nlm.nih.gov/pubmed/27023706", "http://www.ncbi.nlm.nih.gov/pubmed/27678025", "http://www.ncbi.nlm.nih.gov/pubmed/27807285", "http://www.ncbi.nlm.nih.gov/pubmed/27934506" ], "ideal_answer": [ "Verubecestat (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of A\u03b240, A\u03b242, and sAPP\u03b2 (a direct product of BACE1 enzymatic activity)." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504" ], "type": "summary", "id": "589a246a78275d0c4a000031", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The BACE1 inhibitor verubecestat (MK-8931) reduces CNS \u03b2-amyloid in animal models and in Alzheimer's disease patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27807285", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 601, "text": "We show that verubecestat (MK-8931) is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of A\u03b240, A\u03b242, and sAPP\u03b2 (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27807285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A \u03b2-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933948", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity \u03b2-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27934506", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Verubecestat is an inhibitor of \u03b2-secretase being evaluated for the treatment of Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27934506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Verubecestat is an inhibitor of \u03b2-secretase being evaluated for the treatment of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27934506", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1446, "text": "After giving an update on the development and current status of new AD therapeutics, this review will focus on BACE inhibitors and, in particular, will discuss the prospects of verubecestat (MK-8931), which has reached phase III clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27023706", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 591, "text": "Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain A\u03b2 levels in rats and nonhuman primates and CSF A\u03b2 levels in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933948", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 599, "text": "We show that verubecestat (MK-8931) is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of A\u03b240, A\u03b242, and sAPP\u03b2 (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27807285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity \u03b2-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933948", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 938, "text": "Chronic treatment of rats and monkeys with verubecestat achieved exposures >40-fold higher than those being tested in clinical trials in AD patients yet did not elicit many of the adverse effects previously attributed to BACE inhibition, such as reduced nerve myelination, neurodegeneration, altered glucose homeostasis, or hepatotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27807285", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 883, "text": "Expert opinion: Drugs in Phase III clinical development for AD include one inhibitor of the \u03b2-secretase cleaving enzyme (BACE) (verubecestat), three anti-A\u03b2 monoclonal antibodies (solanezumab, gantenerumab, and aducanumab), an inhibitor of receptor for advanced glycation end products (RAGE) (azeliragon) and the combination of cromolyn sodium and ibuprofen (ALZT-OP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27678025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27934506", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The BACE1 inhibitor verubecestat (MK-8931) reduces CNS \u03b2-amyloid in animal models and in Alzheimer's disease patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27807285", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A \u03b2-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933948", "endSection": "title" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1454, "text": "After giving an update on the development and current status of new AD therapeutics, this review will focus on BACE inhibitors and, in particular, will discuss the prospects of verubecestat (MK-8931), which has reached phase III clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27023706", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 592, "text": "Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain A\u03b2 levels in rats and nonhuman primates and CSF A\u03b2 levels in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933948", "endSection": "abstract" } ] }, { "body": "How are triple negative gliomas characterized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23288644", "http://www.ncbi.nlm.nih.gov/pubmed/22890969", "http://www.ncbi.nlm.nih.gov/pubmed/26989023", "http://www.ncbi.nlm.nih.gov/pubmed/23831947", "http://www.ncbi.nlm.nih.gov/pubmed/26061753", "http://www.ncbi.nlm.nih.gov/pubmed/21889777" ], "ideal_answer": [ "of these markers - 1p/19q deletions , mgmt methylation status , and mutations in the idh1 gene - are so potent that a new brain tumor subtype , the \"triple negative\" glioma (1p/19q intact , mgmt unmethylated , idh1 non-mutated) has entered common parlance . ", "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis.", "Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. ", "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. (Funded by the National Institutes of Health and others. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance.", "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance. ", "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative (IDH-/p53-/1p19q-), this last subgroup having the worst prognosis.", "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance. ", "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations", "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance" ], "type": "summary", "id": "58bac5e822d3005309000012", "snippets": [ { "offsetInBeginSection": 1107, "offsetInEndSection": 1310, "text": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21889777", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 878, "text": "Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890969", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 1255, "text": "Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26061753", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1282, "text": "Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288644", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 513, "text": "Few data are available in the literature regarding the relationship between IDH mutations and HIF expression in low-grade gliomas (LGGs), especially in a recently described aggressive molecular subtype: \"triple negative\" (IDH non mutated, 1p 19q non codeleted, p53 expression negative) gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26989023", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 872, "text": "Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890969", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1278, "text": "Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23288644", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 876, "text": "Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890969", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 877, "text": "Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890969", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 514, "text": "Few data are available in the literature regarding the relationship between IDH mutations and HIF expression in low-grade gliomas (LGGs), especially in a recently described aggressive molecular subtype: \"triple negative\" (IDH non mutated, 1p 19q non codeleted, p53 expression negative) gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26989023", "endSection": "abstract" } ] }, { "body": "What is ectopia lentis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25797933", "http://www.ncbi.nlm.nih.gov/pubmed/25939784", "http://www.ncbi.nlm.nih.gov/pubmed/19200529" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0013581", "o": "Ectopia lentis" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0013581", "o": "http://linkedlifedata.com/resource/umls/label/A0052649" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0052649", "o": "Ectopia Lentis" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/1026597", "o": "http://linkedlifedata.com/resource/rxnorm/label/3153153" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3153153", "o": "Ectopia Lentis" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0013581", "o": "http://linkedlifedata.com/resource/umls/label/A12012342" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12012342", "o": "Ectopia lentis" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0013581", "o": "http://linkedlifedata.com/resource/umls/label/A0078970" } ], "ideal_answer": [ "Ectopia Lentis is dislocation of the optic lens in the eye." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004479" ], "type": "summary", "id": "58dc2c698acda3452900001f", "snippets": [ { "offsetInBeginSection": 242, "offsetInEndSection": 268, "text": "bilateral lens dislocation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25797933", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 239, "text": "Clinical manifestations include mental retardation, dislocation of the optic lens (ectopia lentis)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25939784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19200529", "endSection": "abstract" } ] }, { "body": "Can glyburide reduce cerebral edema?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24193798", "http://www.ncbi.nlm.nih.gov/pubmed/25422710", "http://www.ncbi.nlm.nih.gov/pubmed/26463916", "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "http://www.ncbi.nlm.nih.gov/pubmed/24552576", "http://www.ncbi.nlm.nih.gov/pubmed/24671831", "http://www.ncbi.nlm.nih.gov/pubmed/23633925", "http://www.ncbi.nlm.nih.gov/pubmed/17673715", "http://www.ncbi.nlm.nih.gov/pubmed/26268138" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0017628", "o": "glyburide" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0017628", "o": "http://linkedlifedata.com/resource/umls/label/A10769058" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10769058", "o": "GLYBURIDE" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/4815", "o": "http://linkedlifedata.com/resource/rxnorm/label/3163336" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3163336", "o": "GLYBURIDE" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0017628", "o": "http://linkedlifedata.com/resource/umls/label/A0064005" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0064005", "o": "Glyburide" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/4815", "o": "http://linkedlifedata.com/resource/rxnorm/label/1842549" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/1842549", "o": "Glyburide" } ], "ideal_answer": [ "Yes. Glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing and attenuating cerebral edema." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001929", "http://www.biosemantics.org/jochem#4275786", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275786", "http://www.disease-ontology.org/api/metadata/DOID:4724", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005905" ], "type": "yesno", "id": "588482f5e56acf517600000a", "snippets": [ { "offsetInBeginSection": 137, "offsetInEndSection": 411, "text": "Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1486, "text": "CONCLUSIONS: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Glyburide is associated with attenuated vasogenic edema in stroke patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "endSection": "title" }, { "offsetInBeginSection": 134, "offsetInEndSection": 382, "text": "Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1323, "text": "RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level.CONCLUSIONS: Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Pilot study of intravenous glyburide in patients with a large ischemic stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24193798", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "BACKGROUND AND PURPOSE: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24193798", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 222, "text": "Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Glyburide in Treating Malignant Cerebral Edema. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25422710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Glyburide in Treating Malignant Cerebral Edema. Blocking Sulfonyl Urea One (SUR1) Receptors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25422710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "The sulfonylurea receptor 1-regulated NC(Ca-ATP) channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17673715", "endSection": "abstract" }, { "offsetInBeginSection": 1534, "offsetInEndSection": 1678, "text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 901, "text": "In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24552576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Potential of glyburide to reduce intracerebral edema in brain metastases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24552576", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138", "endSection": "title" }, { "offsetInBeginSection": 107, "offsetInEndSection": 209, "text": "Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1706, "text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1189, "text": "RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 223, "text": "Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Exploratory analysis of glyburide as a novel therapy for preventing brain swelling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24671831", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 904, "text": "In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24552576", "endSection": "abstract" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1675, "text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 381, "text": "Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1282, "text": "Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 399, "text": "We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268138", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1690, "text": "Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Glyburide is associated with attenuated vasogenic edema in stroke patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072459", "endSection": "title" } ] }, { "body": "What is the function of gasdermin D?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26482951", "http://www.ncbi.nlm.nih.gov/pubmed/26611636", "http://www.ncbi.nlm.nih.gov/pubmed/27281216", "http://www.ncbi.nlm.nih.gov/pubmed/27932073" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1539620", "o": "http://linkedlifedata.com/resource/umls/label/A20719561" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20719561", "o": "gasdermin D" } ], "ideal_answer": [ "The gasdermin-N domains of the gasdermin proteins can bind membrane lipids, phosphoinositides and cardiolipin to produce membrane-disrupting cytotoxicity." ], "concepts": [ "http://www.uniprot.org/uniprot/GSDMD_MOUSE", "http://www.uniprot.org/uniprot/GSDMD_HUMAN" ], "type": "summary", "id": "58e2467a6fddd3e83e000012", "snippets": [ { "offsetInBeginSection": 33, "offsetInEndSection": 161, "text": "gasdermin D (GSDMD) protein to trigger pyroptosis, a lytic form of cell death that is crucial for immune defences and diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27281216", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 584, "text": "Here we show that the gasdermin-N domains of the gasdermin proteins GSDMD, GSDMA3 and GSDMA can bind membrane lipids, phosphoinositides and cardiolipin, and exhibit membrane-disrupting cytotoxicity in mammalian cells and artificially transformed bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27281216", "endSection": "abstract" } ] }, { "body": "What is TOPAZ1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26358182", "http://www.ncbi.nlm.nih.gov/pubmed/22069478" ], "ideal_answer": [ "TOPAZ1 is a novel germ cell-specific expressed gene conserved during evolution across vertebrates. Its PAZ-domain protein is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line.", "TOPAZ1 (Testis and Ovary-specific PAZ domain gene 1) is a germ cell specific factor that is essential for male meiotic progression. Topaz1 is supposed to have a role during gametogenesis and may be involved in the piRNA pathway and contribute to silencing of transposable elements and maintenance of genome integrity. It is highly conserved in vertebrates." ], "concepts": [ "http://www.uniprot.org/uniprot/TOPZ1_BOVIN", "http://www.uniprot.org/uniprot/TOPZ1_HUMAN", "http://www.uniprot.org/uniprot/TOPZ1_RAT", "http://www.uniprot.org/uniprot/TOPZ1_MOUSE", "http://www.uniprot.org/uniprot/TOPZ1_MACFA", "http://www.uniprot.org/uniprot/TOPZ1_MACMU", "http://www.uniprot.org/uniprot/TOPZ1_SHEEP", "http://www.uniprot.org/uniprot/TOPZ1_CALJA" ], "type": "summary", "id": "587d016ed673c3eb14000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "TOPAZ1, a germ cell specific factor, is essential for male meiotic progression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26358182", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Topaz1 (Testis and Ovary-specific PAZ domain gene 1) is a germ cell specific gene highly conserved in vertebrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26358182", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 423, "text": "Topaz1 is supposed to have a role during gametogenesis and may be involved in the piRNA pathway and contribute to silencing of transposable elements and maintenance of genome integrity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26358182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "TOPAZ1, a novel germ cell-specific expressed gene conserved during evolution across vertebrates", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069478", "endSection": "title" } ] }, { "body": "Which are the symptoms of glucose-6-phosphate dehydrogenase (G6PD) deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24865682", "http://www.ncbi.nlm.nih.gov/pubmed/24372186", "http://www.ncbi.nlm.nih.gov/pubmed/11233775", "http://www.ncbi.nlm.nih.gov/pubmed/20684792", "http://www.ncbi.nlm.nih.gov/pubmed/21336800", "http://www.ncbi.nlm.nih.gov/pubmed/16450734", "http://www.ncbi.nlm.nih.gov/pubmed/750548", "http://www.ncbi.nlm.nih.gov/pubmed/25079187", "http://www.ncbi.nlm.nih.gov/pubmed/25116429", "http://www.ncbi.nlm.nih.gov/pubmed/25949934", "http://www.ncbi.nlm.nih.gov/pubmed/23188", "http://www.ncbi.nlm.nih.gov/pubmed/21302115", "http://www.ncbi.nlm.nih.gov/pubmed/23961874", "http://www.ncbi.nlm.nih.gov/pubmed/23640458", "http://www.ncbi.nlm.nih.gov/pubmed/10745013", "http://www.ncbi.nlm.nih.gov/pubmed/24891465", "http://www.ncbi.nlm.nih.gov/pubmed/18094574", "http://www.ncbi.nlm.nih.gov/pubmed/21784438", "http://www.ncbi.nlm.nih.gov/pubmed/12737943", "http://www.ncbi.nlm.nih.gov/pubmed/26275698", "http://www.ncbi.nlm.nih.gov/pubmed/22829586", "http://www.ncbi.nlm.nih.gov/pubmed/24636884", "http://www.ncbi.nlm.nih.gov/pubmed/19769422", "http://www.ncbi.nlm.nih.gov/pubmed/18450407", "http://www.ncbi.nlm.nih.gov/pubmed/25807896", "http://www.ncbi.nlm.nih.gov/pubmed/26840990", "http://www.ncbi.nlm.nih.gov/pubmed/11793482", "http://www.ncbi.nlm.nih.gov/pubmed/9088998", "http://www.ncbi.nlm.nih.gov/pubmed/10698963", "http://www.ncbi.nlm.nih.gov/pubmed/11271380", "http://www.ncbi.nlm.nih.gov/pubmed/20194698", "http://www.ncbi.nlm.nih.gov/pubmed/23874768", "http://www.ncbi.nlm.nih.gov/pubmed/11261779", "http://www.ncbi.nlm.nih.gov/pubmed/10980404", "http://www.ncbi.nlm.nih.gov/pubmed/19086137", "http://www.ncbi.nlm.nih.gov/pubmed/24711919", "http://www.ncbi.nlm.nih.gov/pubmed/20065266", "http://www.ncbi.nlm.nih.gov/pubmed/22139979", "http://www.ncbi.nlm.nih.gov/pubmed/11842483" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/uniprot/P11413", "o": "http://purl.uniprot.org/uniprot/P11413" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0017757", "o": "G6PD" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_503131343133004B", "o": "G6PD" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0017757", "o": "http://linkedlifedata.com/resource/umls/label/A8256485" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://linkedlifedata.com/resource/drugbank/molecule/1799", "o": "http://purl.uniprot.org/uniprot/P11413" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/drugbank/molecule/1799", "o": "Glucose-6-phosphate 1-dehydrogenase" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/uniprot/P11413", "o": "G6PD_HUMAN" } ], "ideal_answer": [ "Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common symptoms of this condition are:\n1) acute hemolysis, \n2) chronic hemolysis, \n3) neonatal hyperbilirubinemia." ], "exact_answer": [ [ "acute hemolysis" ], [ "chronic hemolysis" ], [ "neonatal hyperbilirubinemia" ] ], "concepts": [ "http://www.uniprot.org/uniprot/G6PD_BUCAI", "http://www.disease-ontology.org/api/metadata/DOID:2862", "http://www.uniprot.org/uniprot/G6PD_CERCA", "http://www.uniprot.org/uniprot/G6PD_CRIGR", "http://www.uniprot.org/uniprot/G6PD_ECOLI", "http://www.uniprot.org/uniprot/G6PD_EMENI", "http://www.uniprot.org/uniprot/G6PD_BUCAP", "http://www.uniprot.org/uniprot/G6PD_HUMAN", "http://www.uniprot.org/uniprot/G6PD_ZYMMO", "http://www.uniprot.org/uniprot/G6PD_MACRO", "http://amigo.geneontology.org/amigo/term/GO:0004345", "http://www.uniprot.org/uniprot/G6PD_ENCCU", "http://www.uniprot.org/uniprot/G6PD_TAKRU", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005954", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005955", "http://www.uniprot.org/uniprot/G6PD_HAEIN", "http://www.uniprot.org/uniprot/G6PD_CYBJA", "http://www.uniprot.org/uniprot/G6PD_ECO57", "http://www.uniprot.org/uniprot/G6PD_DIDVI", "http://www.uniprot.org/uniprot/G6PD_AGGAC", "http://www.uniprot.org/uniprot/G6PD_HELPY", "http://www.uniprot.org/uniprot/G6PD_BOSIN", "http://www.uniprot.org/uniprot/G6PD_GLUOX", "http://www.uniprot.org/uniprot/G6PD_HELPJ", "http://www.uniprot.org/uniprot/G6PD_NOSP7" ], "type": "list", "id": "58c6665602b8c60953000024", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 466, "text": "Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25079187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "Red blood cells carry oxygen in the body and Glucose-6-Phosphate Dehydrogenase protects these cells from oxidative chemicals. If there is a lack of Glucose-6-Phosphate Dehydrogenase, red blood cells can go acute hemolysis. Convulsion is a rare presentation for acute hemolysis due to Glucose-6-Phosphate Dehydrogenase deficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24711919", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 851, "text": "By far the most common form worldwide is the Glucose-6-phosphate deficiency. In the most frequent variants of this disease hemolysis occurs only during stress, imposed for example by infection, \"oxidative\" drugs or after ingestion of fava beans. The most serious clinical complication of the Glucose-6-phosphate deficiency is the rarely observed neonatal icterus. Some enzyme variants can cause chronic hemolysis which is described as chronic nonsperocytic hemolytic anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16450734", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 367, "text": "One limitation of primaquine is that, at certain doses, primaquine can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22829586", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 505, "text": "The 6PGD deficiency was associated with a variable reticulocyte count and recurrent increased unconjugated bilirubinemia without anemia in the propositus, while no clinical or hematological symptoms were evident in her mother.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11233775", "endSection": "abstract" }, { "offsetInBeginSection": 2121, "offsetInEndSection": 2644, "text": "The authors of this article make 5 particular recommendations: (1) Anyone suspected of G6PD deficiency should be screened; (2) exposure to oxidative stressors in these individuals should be avoided; (3) these patients should be informed of risks along with signs and symptoms of an acute hemolytic crisis; (4) the clinician should be able to identify both laboratory and clinical signs of hemolysis; and finally, (5) if an acute hemolytic crisis is identified, the patient should be admitted for close observation and care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19769422", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 816, "text": "None of the patients with or without G6PD deficiency showed symptoms, signs, or laboratory findings indicating hemolysis before administration of the drug and 4 days thereafter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9088998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Kinetic and electrophoretic properties of 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G6PD) from red cells of donors and patients with acute drug hemolytic anemia due to G6PD deficiency were studied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder in which haemolytic anaemia is the major symptom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11271380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116429", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 245, "text": "However, its use is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (risk for haemolytic anaemia).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25807896", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 192, "text": "The role of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Antiplatelet and invasive treatment in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and acute coronary syndrome. The safety of aspirin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25807896", "endSection": "title" } ] }, { "body": "Has the gorilla genome been determined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11592477", "http://www.ncbi.nlm.nih.gov/pubmed/27034376", "http://www.ncbi.nlm.nih.gov/pubmed/22398555", "http://www.ncbi.nlm.nih.gov/pubmed/27435933" ], "ideal_answer": [ "Yes, the gorilla genome has been sequenced." ], "exact_answer": "yes", "type": "yesno", "id": "58dfec676fddd3e83e000006", "snippets": [ { "offsetInBeginSection": 494, "offsetInEndSection": 638, "text": "Starting with human, chimpanzee, gorilla, and orangutan genomes, our software generated an exhaustive data set of 292 ALs (\u223c1 kb each) in \u223c3 h. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27435933", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 258, "text": "We generated a high-quality assembly of the gorilla genome using single-molecule, real-time sequence technology and a string graph de novo assembly algorithm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27034376", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 301, "text": "Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22398555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "DNA sequencing reveals that the genomes of the human, gorilla and chimpanzee share more than 98% homology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11592477", "endSection": "abstract" } ] }, { "body": "Is vemurafenib used for thyroid cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27460442", "http://www.ncbi.nlm.nih.gov/pubmed/27554612", "http://www.ncbi.nlm.nih.gov/pubmed/27754804", "http://www.ncbi.nlm.nih.gov/pubmed/24987354", "http://www.ncbi.nlm.nih.gov/pubmed/23489023", "http://www.ncbi.nlm.nih.gov/pubmed/26751190", "http://www.ncbi.nlm.nih.gov/pubmed/24756795", "http://www.ncbi.nlm.nih.gov/pubmed/26735176", "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "http://www.ncbi.nlm.nih.gov/pubmed/26284586", "http://www.ncbi.nlm.nih.gov/pubmed/22649416", "http://www.ncbi.nlm.nih.gov/pubmed/26176686", "http://www.ncbi.nlm.nih.gov/pubmed/26636651", "http://www.ncbi.nlm.nih.gov/pubmed/27127178", "http://www.ncbi.nlm.nih.gov/pubmed/24262022", "http://www.ncbi.nlm.nih.gov/pubmed/27432558", "http://www.ncbi.nlm.nih.gov/pubmed/25467940" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/rxnorm/id/1147220", "o": "VEMURAFENIB" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C3192263", "o": "http://linkedlifedata.com/resource/umls/label/A20020623" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20020623", "o": "VEMURAFENIB" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/1147220", "o": "http://linkedlifedata.com/resource/rxnorm/label/4224011" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/4224011", "o": "VEMURAFENIB" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/chembl/synonym/691867_Vemurafenib_USAN", "o": "Vemurafenib" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C3192263", "o": "http://linkedlifedata.com/resource/umls/label/A19613644" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A19613644", "o": "Vemurafenib" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C3192263", "o": "http://linkedlifedata.com/resource/umls/label/A19649207" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A19649207", "o": "Vemurafenib" } ], "ideal_answer": [ "Yes. Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:3963", "http://www.disease-ontology.org/api/metadata/DOID:1781", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013964" ], "type": "yesno", "id": "58848ea5e56acf517600000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27460442", "endSection": "title" }, { "offsetInBeginSection": 117, "offsetInEndSection": 314, "text": "Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27460442", "endSection": "abstract" }, { "offsetInBeginSection": 2338, "offsetInEndSection": 2559, "text": "INTERPRETATION: Vemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27460442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "endSection": "title" }, { "offsetInBeginSection": 1685, "offsetInEndSection": 1840, "text": "CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 459, "text": "The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25467940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Use of vemurafenib in anaplastic thyroid carcinoma: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26176686", "endSection": "title" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1361, "text": "Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1369, "text": "Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432558", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1415, "text": "Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26284586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353071", "endSection": "abstract" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1727, "text": "Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27754804", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 729, "text": "Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26284586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27754804", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432558", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26284586", "endSection": "title" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1092, "text": "Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27754804", "endSection": "abstract" } ] }, { "body": "Are mutations in the C9orf72 gene associated with macular degeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26303227", "http://www.ncbi.nlm.nih.gov/pubmed/22228244", "http://www.ncbi.nlm.nih.gov/pubmed/24521566", "http://www.ncbi.nlm.nih.gov/pubmed/27632209", "http://www.ncbi.nlm.nih.gov/pubmed/22892647", "http://www.ncbi.nlm.nih.gov/pubmed/22300873", "http://www.ncbi.nlm.nih.gov/pubmed/22366791", "http://www.ncbi.nlm.nih.gov/pubmed/24442578", "http://www.ncbi.nlm.nih.gov/pubmed/23934648", "http://www.ncbi.nlm.nih.gov/pubmed/27619540", "http://www.ncbi.nlm.nih.gov/pubmed/22673113", "http://www.ncbi.nlm.nih.gov/pubmed/23053135", "http://www.ncbi.nlm.nih.gov/pubmed/24064469" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1428691", "o": "C9orf72" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1428691", "o": "http://linkedlifedata.com/resource/umls/label/A20715582" } ], "ideal_answer": [ "Amyotrophic lateral sclerosis (ALS) is characterized by motor neurone loss resulting in muscle weakness, spasticity and ultimately death. 5-10% are caused by inherited mutations, most commonly C9ORF72, SOD1, TARDBP and FUS." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012162", "http://www.disease-ontology.org/api/metadata/DOID:4448", "http://www.disease-ontology.org/api/metadata/DOID:10871", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057135", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008268", "http://www.disease-ontology.org/api/metadata/DOID:14245", "http://www.disease-ontology.org/api/metadata/DOID:8466" ], "type": "yesno", "id": "58e11bf76fddd3e83e00000c", "snippets": [ { "offsetInBeginSection": 296, "offsetInEndSection": 710, "text": "Over the years, however, growing evidence from clinical, pathological and genetic findings has suggested that ALS and FTD belong to the same clinic-pathological spectrum disorder. This concept has been further supported by the identification of the most common genetic cause for both diseases, an aberrantly expanded hexanucleotide repeat GGGGCC/ CCCCGG sequence located in a non-coding region of the gene C9orf72.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27619540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Amyotrophic lateral sclerosis (ALS) is characterized by motor neurone loss resulting in muscle weakness, spasticity and ultimately death. 5-10% are caused by inherited mutations, most commonly C9ORF72, SOD1, TARDBP and FUS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26303227", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1125, "text": "In this article, we will review the brief characterizations of the C9ORF72 gene, the expansion mutations, the related disorders, and their features, followed by a discussion of the deficiency knowledge of C9ORF72 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23934648", "endSection": "abstract" }, { "offsetInBeginSection": 2374, "offsetInEndSection": 2520, "text": "Mutations in the C9ORF72 gene may be a major cause not only of frontotemporal dementia with motor neuron disease but also of late onset psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22300873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Frontotemporal lobar degeneration (FTLD) is a genetically heterogenous syndrome and has been associated most recently with a hexanucleotide repeat expansion within the C9ORF72 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "An expanded GGGGCC hexanucleotide repeat in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration associated with TDP-43 pathology (FTLD-TDP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Novel TARDBP sequence variant and C9ORF72 repeat expansion in a family with frontotemporal dementia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892647", "endSection": "title" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1027, "text": "There was, as expected, a significant association between C9ORF72 mutations and presence of motor neuron disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22300873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Expansion of a hexanucleotide repeat in the C9ORF72 gene has been identified as the most common pathogenic mutation in families with autosomal dominant frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24064469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "C9ORF72 hexanucleotide repeat number in frontotemporal lobar degeneration: a genotype-phenotype correlation study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24064469", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24442578", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 260, "text": "studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open-reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22228244", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 208, "text": "GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene was recently identified as an important cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673113", "endSection": "abstract" } ] }, { "body": "What is the Genome 10K Project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25689317", "http://www.ncbi.nlm.nih.gov/pubmed/22897955" ], "ideal_answer": [ "The Genome 10K Project was established in 2009 by a consortium of biologists and genome scientists determined to facilitate the sequencing and analysis of the complete genomes of 10,000 vertebrate species." ], "type": "summary", "id": "58dff3f06fddd3e83e000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The Genome 10K Project was established in 2009 by a consortium of biologists and genome scientists determined to facilitate the sequencing and analysis of the complete genomes of 10,000 vertebrate species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25689317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The Genome 10K project aims to sequence the genomes of 10,000 vertebrates, representing approximately one genome for each vertebrate genus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22897955", "endSection": "abstract" } ] }, { "body": "Which gene controls the expression of GATA-1 isoforms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12202480", "http://www.ncbi.nlm.nih.gov/pubmed/24453067", "http://www.ncbi.nlm.nih.gov/pubmed/20304827" ], "ideal_answer": [ "In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript.", "A transcriptional network has been reported, in which PU.1 positively regulates GATA-1 expression in mast cell development.", "In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation.", "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development.", "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. ", "Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s." ], "exact_answer": [ "PU.1" ], "type": "factoid", "id": "58e75d483e8b6dc87c000005", "snippets": [ { "offsetInBeginSection": 127, "offsetInEndSection": 272, "text": "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24453067", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 320, "text": "In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20304827", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 611, "text": "This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20304827", "endSection": "abstract" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1186, "text": "Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20304827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12202480", "endSection": "title" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1034, "text": "Furthermore, we observe that in PU.1(-/-) fetal liver cells, low levels of the IE GATA-1 isoform is expressed, but the variant IB isoform is absent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20304827", "endSection": "abstract" }, { "offsetInBeginSection": 1587, "offsetInEndSection": 1813, "text": "Our findings identify novel combinatorial protein-protein interactions for GATA-1, PU.1, and C/EBPepsilon isoforms in eosinophil gene transcription that include GATA-1/PU.1 synergy and repressor activity for C/EBPepsilon(27)..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12202480", "endSection": "abstract" } ] }, { "body": "What is MIRA-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27009155", "http://www.ncbi.nlm.nih.gov/pubmed/26384656", "http://www.ncbi.nlm.nih.gov/pubmed/25881900", "http://www.ncbi.nlm.nih.gov/pubmed/25623529" ], "ideal_answer": [ "MIRA-seq is a reliable, genome-scale DNA methylation analysis platform for scoring DNA methylation differences at CpG-rich genomic regions. The method is not limited by primer or probe design and is cost effective." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:1905642", "http://amigo.geneontology.org/amigo/term/GO:0044029", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899", "http://amigo.geneontology.org/amigo/term/GO:0044027", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000070593", "http://amigo.geneontology.org/amigo/term/GO:0044728" ], "type": "summary", "id": "588fd7cded9bbee70d000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "MIRA-seq for DNA methylation analysis of CpG islands.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25881900", "endSection": "title" }, { "offsetInBeginSection": 620, "offsetInEndSection": 834, "text": "MIRA-seq is a reliable, genome-scale DNA methylation analysis platform for scoring DNA methylation differences at CpG-rich genomic regions. The method is not limited by primer or probe design and is cost effective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25881900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Using MIRA-seq, we have characterized the DNA methylome of metastatic melanoma and normal melanocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26384656", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 538, "text": "Global gene expression was measured by RNA-Seq, while an epigenetic basis for expression differences was examined by methylated CpG island recovery assay sequencing (MIRA-Seq) analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009155", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 540, "text": "Global gene expression was measured by RNA-Seq, while an epigenetic basis for expression differences was examined by methylated CpG island recovery assay sequencing (MIRA-Seq) analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "MIRA-seq for DNA methylation analysis of CpG islands.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25881900", "endSection": "title" }, { "offsetInBeginSection": 576, "offsetInEndSection": 715, "text": "MIRA-seq is a reliable, genome-scale DNA methylation analysis platform for scoring DNA methylation differences at CpG-rich genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25881900", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1129, "text": "Despite extensive breed differences in the transcriptome, MIRA-Seq unveiled relatively similar patterns of genome-wide DNA methylation between breeds, with an overall hypomethylation of gene promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009155", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1470, "text": "Methylated CpG island recovery assay sequencing (MIRA-Seq) revealed numerous methylation peaks spread across the genome, combined with an overall hypomethylation of gene promoter regions, and a remarkable similarity, except for 20 regions along the genome, between the fibroblasts collected at the two ages from the same animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25623529", "endSection": "abstract" } ] }, { "body": "How does Ssu72 mediate gene looping?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24945319", "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "http://www.ncbi.nlm.nih.gov/pubmed/17803944", "http://www.ncbi.nlm.nih.gov/pubmed/16319194", "http://www.ncbi.nlm.nih.gov/pubmed/26119342", "http://www.ncbi.nlm.nih.gov/pubmed/12704082" ], "ideal_answer": [ "Investigation of chromosome folding in mutants confirms roles for RSC, \"gene looping\" factor Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and the N-terminal tail of H4 in folding of the yeast genome. The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP. We propose a model for RNAP II transcription in which promoter and terminator regions are juxtaposed, and that the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation. The first 300 amino acids of Pta1 are sufficient for interactions with Ssu72, which is needed for pre-mRNA cleavage. ", "In RNAP II transcription, promoter and terminator regions are juxtaposed and the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation. These interactions are transcription-dependent, require the Ssu72 and Pta1 components of the CPF 3'-end processing complex, and require the phosphatase activity of Ssu72.", "tfiib crosslinks to both the promoter and terminator regions of the pma1 and blm10 genes, and its association with the terminator, but not the promoter, is adversely affected by e62k and by depletion of the ssu72 component of the cpf 3' end processing complex, and is independent of tbp.", "Investigation of chromosome folding in mutants confirms roles for RSC, \"gene looping\" factor Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and the N-terminal tail of H4 in folding of the yeast genome. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP. We propose a model for RNAP II transcription in which promoter and terminator regions are juxtaposed, and that the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation. The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing These interactions are transcription-dependent, require the Ssu72 and Pta1 components of the CPF 3'-end processing complex, and require the phosphatase activity of Ssu72. Furthermore, different regions of Pta1 interact with the CPF subunits Ssu72, Pti1, and Ysh1, supporting the idea that Pta1 acts as a scaffold to organize CPF.", "The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing" ], "type": "summary", "id": "58af14ae717cd3f655000001", "snippets": [ { "offsetInBeginSection": 688, "offsetInEndSection": 891, "text": "Investigation of chromosome folding in mutants confirms roles for RSC, \"gene looping\" factor Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and the N-terminal tail of H4 in folding of the yeast genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26119342", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 819, "text": "Furthermore, different regions of Pta1 interact with the CPF subunits Ssu72, Pti1, and Ysh1, supporting the idea that Pta1 acts as a scaffold to organize CPF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "title" }, { "offsetInBeginSection": 820, "offsetInEndSection": 937, "text": "The first 300 amino acids of Pta1 are sufficient for interactions with Ssu72, which is needed for pre-mRNA cleavage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1392, "text": "These findings suggest that the amino terminus of Pta1 has an inhibitory effect and that this effect can be neutralized through the interaction with Ssu72.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 799, "text": "TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17803944", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 756, "text": " These interactions are transcription-dependent, require the Ssu72 and Pta1 components of the CPF 3'-end processing complex, and require the phosphatase activity of Ssu72.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16319194", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 1027, "text": "We propose a model for RNAP II transcription in which promoter and terminator regions are juxtaposed, and that the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16319194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "title" }, { "offsetInBeginSection": 469, "offsetInEndSection": 661, "text": "The pta1-Delta75 mutant is defective for snoRNA termination, RNA polymerase II C-terminal domain Ser5-P dephosphorylation, and gene looping but is fully functional for mRNA 3'-end processing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1325, "text": "We conclude that Swd2.2 opposes condensin-mediated chromosome condensation by facilitating the function of the two CPF-associated phosphatases PP1 and Ssu72.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24945319", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1286, "text": "Based on the interactions of Ssu72 and Sub1 with both the Pta1 of CPF and the TFIIB component of the initiation complex, we present a model describing how these novel connections between the transcription and 3' end processing machineries might facilitate transitions in the RNAP II transcription cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12704082", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1128, "text": "By the degron-mediated depletion of Pta1, we show that the removal of this essential region leads to a loss of Ssu72, yet surprisingly, in vitro cleavage and polyadenylation remain efficient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 660, "text": "The pta1-Delta75 mutant is defective for snoRNA termination, RNA polymerase II C-terminal domain Ser5-P dephosphorylation, and gene looping but is fully functional for mRNA 3'-end processing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19188448", "endSection": "abstract" } ] }, { "body": "Is the number of described human nuclear mutations less than 50000?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22948725", "http://www.ncbi.nlm.nih.gov/pubmed/20569258", "http://www.ncbi.nlm.nih.gov/pubmed/24077912" ], "ideal_answer": [ "No, The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database)." ], "exact_answer": "no", "type": "yesno", "id": "58e26ede6fddd3e83e000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20569258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "The Human Gene Mutation Database (HGMD\u00ae) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24077912", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 778, "text": "By March 2012, the database contained in excess of 123,600 different lesions (HGMD Professional release 2012.1) detected in 4,514 different nuclear genes, with new entries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22948725", "endSection": "abstract" } ] }, { "body": "What is the role of peptide aptamers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21224349", "http://www.ncbi.nlm.nih.gov/pubmed/22949372", "http://www.ncbi.nlm.nih.gov/pubmed/25699094", "http://www.ncbi.nlm.nih.gov/pubmed/21838684", "http://www.ncbi.nlm.nih.gov/pubmed/25238402", "http://www.ncbi.nlm.nih.gov/pubmed/18186614", "http://www.ncbi.nlm.nih.gov/pubmed/23785412", "http://www.ncbi.nlm.nih.gov/pubmed/11071782", "http://www.ncbi.nlm.nih.gov/pubmed/8755498", "http://www.ncbi.nlm.nih.gov/pubmed/17189388", "http://www.ncbi.nlm.nih.gov/pubmed/25801767", "http://www.ncbi.nlm.nih.gov/pubmed/19377984", "http://www.ncbi.nlm.nih.gov/pubmed/15037656", "http://www.ncbi.nlm.nih.gov/pubmed/19295259", "http://www.ncbi.nlm.nih.gov/pubmed/17574575", "http://www.ncbi.nlm.nih.gov/pubmed/16581027", "http://www.ncbi.nlm.nih.gov/pubmed/19895821", "http://www.ncbi.nlm.nih.gov/pubmed/18195017", "http://www.ncbi.nlm.nih.gov/pubmed/16751801", "http://www.ncbi.nlm.nih.gov/pubmed/12842895", "http://www.ncbi.nlm.nih.gov/pubmed/11641783", "http://www.ncbi.nlm.nih.gov/pubmed/18314488", "http://www.ncbi.nlm.nih.gov/pubmed/23579184", "http://www.ncbi.nlm.nih.gov/pubmed/18243349", "http://www.ncbi.nlm.nih.gov/pubmed/25966787", "http://www.ncbi.nlm.nih.gov/pubmed/25230811", "http://www.ncbi.nlm.nih.gov/pubmed/22503683", "http://www.ncbi.nlm.nih.gov/pubmed/20653933", "http://www.ncbi.nlm.nih.gov/pubmed/18265211", "http://www.ncbi.nlm.nih.gov/pubmed/24478452", "http://www.ncbi.nlm.nih.gov/pubmed/12530529", "http://www.ncbi.nlm.nih.gov/pubmed/19377987", "http://www.ncbi.nlm.nih.gov/pubmed/25963836", "http://www.ncbi.nlm.nih.gov/pubmed/19320493", "http://www.ncbi.nlm.nih.gov/pubmed/10439043", "http://www.ncbi.nlm.nih.gov/pubmed/15231297", "http://www.ncbi.nlm.nih.gov/pubmed/15952909", "http://www.ncbi.nlm.nih.gov/pubmed/19377988", "http://www.ncbi.nlm.nih.gov/pubmed/16731923", "http://www.ncbi.nlm.nih.gov/pubmed/18336207", "http://www.ncbi.nlm.nih.gov/pubmed/9222505" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/595798", "o": "http://linkedlifedata.com/resource/rxnorm/label/3218865" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3218865", "o": "Peptide Aptamers" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "Aptamers, Peptide" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "http://linkedlifedata.com/resource/umls/label/A17937093" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17937093", "o": "Aptamers, Peptide" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/595798", "o": "http://linkedlifedata.com/resource/rxnorm/label/3111176" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3111176", "o": "Aptamers, Peptide" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1567956", "o": "http://linkedlifedata.com/resource/umls/label/A17888724" } ], "ideal_answer": [ "Peptide aptamers are artificial short peptides which are able to specifically bind to defined functional domains, track, and inhibit a given target molecule with high affinity, even molecules with poor immunogenicity or high toxicity. They represent a remarkable alternative to antibodies in many different applications." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052158", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010455" ], "type": "summary", "id": "58d131218acda34529000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Peptide aptamers: The versatile role of specific protein function inhibitors in plant biotechnology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25966787", "endSection": "title" }, { "offsetInBeginSection": 215, "offsetInEndSection": 485, "text": " These artificial short peptides are able to specifically bind, track, and inhibit a given target molecule with high affinity, even molecules with poor immunogenicity or high toxicity, and represent a remarkable alternative to antibodies in many different applications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25966787", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 696, "text": "To inhibit the oncogenic action of Stat3 in tumor cells, we have selected short peptides, so-called peptide aptamers, which specifically interact with defined functional domains of this transcription factor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15037656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Aptasensors utilize aptamers as bioreceptors. Aptamers are highly efficient, have a high specificity and are reusable. Within the biosensor the aptamers are immobilized to maximize their access to target molecules. Knowledge of the orientation and location of the aptamer and peptide during binding could be gained through computational modeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963836", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 743, "text": "Understanding orientation and location of the binding region for a peptide-aptamer complex is critical in their biosensor applicability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963836", "endSection": "abstract" }, { "offsetInBeginSection": 2171, "offsetInEndSection": 2435, "text": " Our study clearly demonstrates the ability of MD simulations to obtain molecular insights for peptide-aptamer binding, and to provide details on the orientation and location of binding between the peptide-aptamer that can be instrumental in biosensor development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Peptide aptamers are artificial short peptides that potentially interfere with the biological roles of their target proteins; however, this technology has not yet been applied to plant functional genomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230811", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 436, "text": "To extend such strategies we selected peptide aptamers binding to PrP from a combinatorial peptide library presented on the Escherichia coli thioredoxin A (trxA) protein as a scaffold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574575", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1277, "text": "These peptide aptamers retained their binding properties to PrPc and, depending on peptide sequence and C-terminal modification, interfered with endogenous PrPSc conversion upon expression in prion-infected cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574575", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 706, "text": "Binding to the nonfarnesylated peptide was at least 10-fold weaker, showing that the aptamers can recognize the hydrophobic farnesyl moiety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9222505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Peptide aptamers: exchange of the thioredoxin-A scaffold by alternative platform proteins and its influence on target protein binding.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12530529", "endSection": "title" }, { "offsetInBeginSection": 190, "offsetInEndSection": 351, "text": "Typically, peptide aptamers are generated by screening a randomized peptide expression library, displayed from the Escherichia coli thioredoxin A (TrxA) protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12530529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Peptide aptamers define distinct EB1- and EB3-binding motifs and interfere with microtubule dynamics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24478452", "endSection": "title" }, { "offsetInBeginSection": 222, "offsetInEndSection": 382, "text": "Reverse analysis with peptide aptamers involves isolating aptamers that interact with a specific protein and monitoring the resulting aptamer-induced phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18265211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "Peptide aptamers are combinatorial protein reagents that bind to targets with a high specificity and a strong affinity thus providing a molecular tool kit for modulating the function of their targets in vivo.Here we report the isolation of a peptide aptamer named swiggle that interacts with the very short (21 amino acid long) intracellular domain of membrane type 1-metalloproteinase (MT1-MMP), a key cell surface protease involved in numerous and crucial physiological and pathological cellular events", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20653933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Peptide aptamers are simple structures, often made up of a single-variable peptide loop constrained within a constant scaffold protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19895821", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 461, "text": "Peptide aptamers are small peptide sequences that have been selected to recognise a predetermined target protein domain and are potentially able to interfere with its function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15952909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Aptamers, including DNA, RNA and peptide aptamers, are a group of promising recognition units that can specifically bind to target molecules and cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25699094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Aptamers are a group of molecules, which can specifically bind, track, and inhibit target molecules, comprising DNA aptamers, RNA aptamers, and peptide aptamers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22949372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Peptide aptamers: The versatile role of specific protein function inhibitors in plant biotechnology", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25966787", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Peptide aptamers are small proteins containing a randomized peptide sequence embedded into a stable protein scaffold, such as Thioredoxin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23785412", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 822, "text": "Peptide aptamers can subsequently be used to guide the discovery of small molecule drugs specific for these molecular surfaces.Here, we present a high-throughput screening assay that identifies small molecules that displace interactions between proteins and their cognate peptide aptamers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19377984", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 443, "text": "These peptide aptamers are target-specific peptides expressed within a protein scaffold engineered from the human protease inhibitor stefin A. The scaffold provides stability to the inserted peptides and increases their binding affinity owing to the resulting three-dimensional constraints", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18186614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Isolation of Peptide aptamers to target protein function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19377987", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Peptide aptamers with binding specificity for the intracellular domain of the ErbB2 receptor interfere with AKT signaling and sensitize breast cancer cells to Taxol.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17189388", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21224349", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Peptide aptamers targeting the hepatitis B virus core protein: a new class of molecules with antiviral activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11641783", "endSection": "title" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1776, "text": "These data highlight the utility of peptide aptamers to identify novel binding interfaces and highlight a role for MAP1B in DAPK-1-dependent signaling in autophagy and membrane blebbing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18195017", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 588, "text": "Therapeutic application depends on binding specificities and affinities, as well as on the production and purification characteristics of the peptide aptamers and their delivery into cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18314488", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 407, "text": "While antibodies are known to recognize the sequence and conformation of protein surface features (epitopes), very little is known about the precise interactions between aptamers and their epitopes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8755498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Monomeric recombinant peptide aptamers are required for efficient intracellular uptake and target inhibition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18314488", "endSection": "title" }, { "offsetInBeginSection": 423, "offsetInEndSection": 575, "text": "The use of small peptide aptamers to competitively inhibit protein interaction and function is becoming increasingly recognized as a powerful technique.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24478452", "endSection": "abstract" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 1533, "text": "For the first time, we show that trxA-based peptide aptamers can be targeted to the secretory pathway, thereby not losing the affinity for their target protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574575", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1047, "text": "Moreover, the aptamers appeared to be able to bind peptides with different solution conformations, implying an induced fit mechanism for binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8755498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Peptide aptamers are small proteins containing a randomized peptide sequence embedded into a stable protein scaffold, such as Thioredoxin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23785412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Peptide aptamers are the newest in the class of \"genetic\" agents that aid in the analysis of cellular processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18265211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Peptide aptamers: The versatile role of specific protein function inhibitors in plant biotechnology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25966787", "endSection": "title" }, { "offsetInBeginSection": 637, "offsetInEndSection": 892, "text": "Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19377988", "endSection": "abstract" } ] }, { "body": "Which are the clinical symptoms of left ventricular noncompaction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27274374", "http://www.ncbi.nlm.nih.gov/pubmed/15458689", "http://www.ncbi.nlm.nih.gov/pubmed/11858389", "http://www.ncbi.nlm.nih.gov/pubmed/19218740", "http://www.ncbi.nlm.nih.gov/pubmed/24231893", "http://www.ncbi.nlm.nih.gov/pubmed/20347493", "http://www.ncbi.nlm.nih.gov/pubmed/23258208", "http://www.ncbi.nlm.nih.gov/pubmed/20860157", "http://www.ncbi.nlm.nih.gov/pubmed/23633270", "http://www.ncbi.nlm.nih.gov/pubmed/22949776", "http://www.ncbi.nlm.nih.gov/pubmed/23196658", "http://www.ncbi.nlm.nih.gov/pubmed/17479651", "http://www.ncbi.nlm.nih.gov/pubmed/9005281", "http://www.ncbi.nlm.nih.gov/pubmed/21987083", "http://www.ncbi.nlm.nih.gov/pubmed/24132556", "http://www.ncbi.nlm.nih.gov/pubmed/10824732", "http://www.ncbi.nlm.nih.gov/pubmed/23843353", "http://www.ncbi.nlm.nih.gov/pubmed/25290726", "http://www.ncbi.nlm.nih.gov/pubmed/23117287", "http://www.ncbi.nlm.nih.gov/pubmed/24826276", "http://www.ncbi.nlm.nih.gov/pubmed/22009732", "http://www.ncbi.nlm.nih.gov/pubmed/23914034", "http://www.ncbi.nlm.nih.gov/pubmed/22235038", "http://www.ncbi.nlm.nih.gov/pubmed/22773171" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "Symptoms" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A0788385" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0788385", "o": "SYMPTOMS" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A11838788" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11838788", "o": "Symptoms" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A7164206" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7164206", "o": "Symptoms" } ], "ideal_answer": [ "The clinical symptoms of left ventricular noncompaction are:\n1) heart failure, \n2) systemic thromboembolic events, \n3) ventricular arrhythmias and\n4) sudden cardiac death." ], "exact_answer": [ [ "heart failure" ], [ "systemic thromboembolic events", "systemic thromboembolism" ], [ "ventricular arrhythmias" ], [ "sudden cardiac death" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016277", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018754", "http://www.disease-ontology.org/api/metadata/DOID:0060480", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018487" ], "type": "list", "id": "58d8e9bd8acda3452900000b", "snippets": [ { "offsetInBeginSection": 188, "offsetInEndSection": 377, "text": "Perioperative management of the patient with LVNC might be challenging due to the clinical symptoms of heart failure, systemic thromboembolic events, and fatal left ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27274374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Left ventricular noncompaction cardiomyopathy is a rare type of congenital cardiomyopathy characterized by prematurely arrested compaction of the endocardial and myocardial fibers and the progressive deterioration of left ventricular contractility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196658", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 590, "text": "Clinical features associated with LVNC vary in asymptomatic and symptomatic patients, and include the potential for heart failure, conduction defects (eg, left bundle branch block), supraventricular and ventricular arrhythmias, thromboembolic events, and sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25290726", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1328, "text": "The clinical presentations are variable ranging from asymptomatic patients to patients who develop ventricular arrhythmias, thromboembolism, heart failure, and sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24132556", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 546, "text": "The clinical presentation and the natural history of LVNC are highly variable, ranging from no symptoms to congestive heart failure, arrhythmias, and systemic thromboemboli. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23117287", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 606, "text": "The clinical manifestations of the disease are variable, ranging from no symptoms to signs of heart failure, systemic emboli, and ventricular arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773171", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 414, "text": "We describe the case of a 62-year-old woman who presented with symptoms of heart failure secondary to left ventricular noncompaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22949776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Multiple left ventricular thrombi in a patient with left ventricular noncompaction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22949776", "endSection": "title" }, { "offsetInBeginSection": 146, "offsetInEndSection": 578, "text": "We present three children with myocardial noncompaction: one male with isolated left ventricular noncompaction, another with right ventricular noncompaction and dysplastic tricuspid valve, and the last with left ventricular noncompaction, ventricular septal defect and coarctation of aorta, to stress especially the different clinical forms of the disorder and the importance of early diagnosis, as it may result in a fatal outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17479651", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 443, "text": "Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death.We retrospectively reviewed all children diagnosed with left ventricular noncompaction at Texas Childrens Hospital from January 1990 to January 2009", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633270", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 417, "text": "We describe the case of a 62-year-old woman who presented with symptoms of heart failure secondary to left ventricular noncompaction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22949776", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1273, "text": "Left ventricular noncompaction (LVNC) and dilated CMP are the most common cardiac phenotypes reported and can lead to symptoms of heart failure as well as ventricular arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23843353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Multiple left ventricular thrombi in a patient with left ventricular noncompaction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22949776", "endSection": "title" }, { "offsetInBeginSection": 172, "offsetInEndSection": 295, "text": "Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633270", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 513, "text": "Clinical symptoms include signs of left ventricular systolic dysfunction even to the point of heart failure, ventricular arrhythmias, and embolic events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10824732", "endSection": "abstract" } ] }, { "body": "What is the Glasgow Coma score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21831280", "http://www.ncbi.nlm.nih.gov/pubmed/25834958", "http://www.ncbi.nlm.nih.gov/pubmed/26295284", "http://www.ncbi.nlm.nih.gov/pubmed/23022643", "http://www.ncbi.nlm.nih.gov/pubmed/11332457" ], "ideal_answer": [ "Glasgow coma sore is used to determine injury severity on admission to a hospital emergency department or by the duration of unconsciousness." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015600" ], "type": "summary", "id": "58cdbbd102b8c60953000045", "snippets": [ { "offsetInBeginSection": 423, "offsetInEndSection": 543, "text": " Injury severity was determined by the Glasgow Coma Scale (GCS) score on admission or by the duration of unconsciousness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26295284", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 678, "text": "Severity analysis was based on the Glasgow Coma Scale and Injury Severity Scor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25834958", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 775, "text": "The strongest correlations were found between the Glasgow coma score and quality of life (r\u00a0= 0.236, P\u00a0= 0.0001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022643", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1420, "text": "By accepting the Glasgow Coma Scale as a gold standard for classification of the level of coma, we can confirm satisfactory measuring qualities for the Vienna Vigilance Score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11332457", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 399, "text": "Our aim in this study was to assess whether the new Glasgow Coma Scale, Age, and Systolic Blood Pressure (GAP) scoring system, which is a modification of the Mechanism, Glasgow Coma Scale, Age, and Arterial Pressure (MGAP) scoring system, better predicts in-hospital mortality and can be applied more easily than previous trauma scores among trauma patients in the emergency department", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21831280", "endSection": "abstract" } ] }, { "body": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26449414", "http://www.ncbi.nlm.nih.gov/pubmed/27082776", "http://www.ncbi.nlm.nih.gov/pubmed/26872887", "http://www.ncbi.nlm.nih.gov/pubmed/27575436", "http://www.ncbi.nlm.nih.gov/pubmed/25516695", "http://www.ncbi.nlm.nih.gov/pubmed/25816811", "http://www.ncbi.nlm.nih.gov/pubmed/27913536", "http://www.ncbi.nlm.nih.gov/pubmed/26559317", "http://www.ncbi.nlm.nih.gov/pubmed/25494843", "http://www.ncbi.nlm.nih.gov/pubmed/27789605", "http://www.ncbi.nlm.nih.gov/pubmed/27659071", "http://www.ncbi.nlm.nih.gov/pubmed/25431993", "http://www.ncbi.nlm.nih.gov/pubmed/26069913", "http://www.ncbi.nlm.nih.gov/pubmed/27697443", "http://www.ncbi.nlm.nih.gov/pubmed/27399455", "http://www.ncbi.nlm.nih.gov/pubmed/26627486", "http://www.ncbi.nlm.nih.gov/pubmed/27147456", "http://www.ncbi.nlm.nih.gov/pubmed/27895055", "http://www.ncbi.nlm.nih.gov/pubmed/26686866", "http://www.ncbi.nlm.nih.gov/pubmed/26519420", "http://www.ncbi.nlm.nih.gov/pubmed/25387210" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0003295", "o": "antidote" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0003295", "o": "http://linkedlifedata.com/resource/umls/label/A17973253" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17973253", "o": "Antidote" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/930", "o": "http://linkedlifedata.com/resource/rxnorm/label/30155" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/30155", "o": "Antidote" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/rxnorm/id/99104", "o": "Coagulation factor inhibitor" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/99104", "o": "http://linkedlifedata.com/resource/rxnorm/label/743388" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0003295", "o": "http://linkedlifedata.com/resource/umls/label/A17925206" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17925206", "o": "Antidote [EPC]" } ], "ideal_answer": [ "Andexanet alfa is a specific reversal agent for Factor Xa inhibitors.", "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. ", "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.", "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. ", "andexanet alfa is a factor xa (fxa) decoy that binds to direct and indirect inhibitors in phase iii trials in healthy volunteers , andexanet alfa reduced anti-fxa activity by more than 90% , reduced the concentration of unbound direct fxa inhibitor , and inhibited thrombin generation . andexanet is an antidote targeted to reverse the oral direct factor xa inhibitors as well as the indirect inhibitor enoxaparin. . ", "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. In Phase III trials in healthy volunteers, andexanet alfa reduced anti-FXa activity by more than 90%, reduced the concentration of unbound direct FXa inhibitor, and inhibited thrombin generation. Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. ", "Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban). Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors. Antidotes that experimentally reverse the anti-coagulant effect of dabigatran (Idarucizumab; BI 655075; Boehringer Ingelheim); of rivaroxaban, apixaban, or edoxaban (Andexanet alfa, r-Antidote, PRT064445; Portola Pharmaceuticals) or of all DOACs (Aripazine, PER-977, ciraparantag; Perosphere Inc.) are discussed. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively.", "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly.", "Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.", "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Andexanet alfa is a factor Xa (FXa) decoy that binds to direct and indirect FXa inhibitors." ], "exact_answer": [ "Factor Xa", "Xa" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000925", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000931", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019774" ], "type": "factoid", "id": "5880b073c872c95565000003", "snippets": [ { "offsetInBeginSection": 642, "offsetInEndSection": 789, "text": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26449414", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1229, "text": "Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26627486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26686866", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Andexanet alfa is a specific reversal agent for Factor Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26686866", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 440, "text": "In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26686866", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1330, "text": "Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26872887", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1034, "text": "Andexanet alfa is a factor Xa (FXa) decoy that binds to direct and indirect FXa inhibitors. In Phase III trials in healthy volunteers, andexanet alfa reduced anti-FXa activity by more than 90%, reduced the concentration of unbound direct FXa inhibitor, and inhibited thrombin generation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27147456", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 938, "text": "Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25494843", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1601, "text": "Recent results from phase 3/4 studies demonstrate efficacy for an antidote to dabigatran (idarucizumab, a monoclonal antibody fragment with specificity for dabigatran) and an antidote to factor Xa inhibitors (andexanet alfa, a recombinant and inactive form of factor Xa that binds inhibitors).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27913536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "176\u2003Andexanet Alfa: An Investigational Universal Antidote for Reversal of Anticoagulation of Factor Xa Inhibitors in Healthy Human Volunteers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399455", "endSection": "title" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1322, "text": "Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26872887", "endSection": "abstract" }, { "offsetInBeginSection": 638, "offsetInEndSection": 785, "text": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26449414", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 282, "text": "Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399455", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 352, "text": "With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26069913", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 354, "text": "With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26069913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26559317", "endSection": "title" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1212, "text": "Specific reversal agents are currently under development (idarucizumab for dabigatran, andexanet alfa for Xa inhibitors, and PER977 for both Xa- and thrombin inhibitors), which will facilitate clinical management of severe bleeding and emergency surgery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25431993", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 355, "text": "With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26069913", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 981, "text": "Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25494843", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 284, "text": "Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399455", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1389, "text": "Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27082776", "endSection": "abstract" }, { "offsetInBeginSection": 1673, "offsetInEndSection": 1968, "text": "New antidotes are being explored, including a mouse monoclonal antibody to dabigatran; andexanet alfa, a potential universal factor Xa inhibitor reversal agent; and a synthetic small molecule (PER977) that may be effective for the reversal of factor Xa inhibitors and direct thrombin inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26559317", "endSection": "title" }, { "offsetInBeginSection": 699, "offsetInEndSection": 857, "text": "Currently, two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "176\u2003Andexanet Alfa: An Investigational Universal Antidote for Reversal of Anticoagulation of Factor Xa Inhibitors in Healthy Human Volunteers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399455", "endSection": "title" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1608, "text": "Recent results from phase 3/4 studies demonstrate efficacy for an antidote to dabigatran (idarucizumab, a monoclonal antibody fragment with specificity for dabigatran) and an antidote to factor Xa inhibitors (andexanet alfa, a recombinant and inactive form of factor Xa that binds inhibitors).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27913536", "endSection": "abstract" } ] }, { "body": "Which is the main cause of the Patau syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18467377", "http://www.ncbi.nlm.nih.gov/pubmed/23613355", "http://www.ncbi.nlm.nih.gov/pubmed/17603803", "http://www.ncbi.nlm.nih.gov/pubmed/14506431", "http://www.ncbi.nlm.nih.gov/pubmed/6458983", "http://www.ncbi.nlm.nih.gov/pubmed/24340511", "http://www.ncbi.nlm.nih.gov/pubmed/12762245", "http://www.ncbi.nlm.nih.gov/pubmed/24993362", "http://www.ncbi.nlm.nih.gov/pubmed/18253026", "http://www.ncbi.nlm.nih.gov/pubmed/12393964", "http://www.ncbi.nlm.nih.gov/pubmed/20537076", "http://www.ncbi.nlm.nih.gov/pubmed/19408854", "http://www.ncbi.nlm.nih.gov/pubmed/2325123", "http://www.ncbi.nlm.nih.gov/pubmed/20641042", "http://www.ncbi.nlm.nih.gov/pubmed/23949924", "http://www.ncbi.nlm.nih.gov/pubmed/26034714", "http://www.ncbi.nlm.nih.gov/pubmed/24564826", "http://www.ncbi.nlm.nih.gov/pubmed/23622175", "http://www.ncbi.nlm.nih.gov/pubmed/20584846", "http://www.ncbi.nlm.nih.gov/pubmed/25459971", "http://www.ncbi.nlm.nih.gov/pubmed/11885075", "http://www.ncbi.nlm.nih.gov/pubmed/21344634", "http://www.ncbi.nlm.nih.gov/pubmed/2348978" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0152095", "o": "http://linkedlifedata.com/resource/umls/label/A18670259" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18670259", "o": "syndrome patau" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0152095", "o": "http://linkedlifedata.com/resource/umls/label/A0574493" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0574493", "o": "Patau syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0152095", "o": "http://linkedlifedata.com/resource/umls/label/A18474937" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18474937", "o": "Patau syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0152095", "o": "http://linkedlifedata.com/resource/umls/label/A18577308" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0152095", "o": "Trisomy 13" } ], "ideal_answer": [ "Patau syndrome is caused by trisomy 13." ], "exact_answer": [ "Trisome 13" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002882", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:11665" ], "type": "factoid", "id": "58da111c8acda34529000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Trisomy 13, or Patau syndrome is a rare chromosomal disorder characterized by a triad of cleft lip and palate, postaxial polydactyly and microcephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21344634", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 308, "text": "Mosaic trisomy 13 is very rare, it occurs in only 5% of all patients with trisomy 13 phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21344634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patau syndrome) are compatible with postnatal survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18253026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "We describe the management of the eyelid anomaly associated with Patau syndrome. Trisomy 13 is the genotype of the syndrome's phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14506431", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 400, "text": "This article identifies the causes and manifestations of most of these trisomies: trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), and trisomy 21 (Down syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11885075", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 248, "text": "WHS is caused by a deletion of 4p16, while Patau syndrome is caused by trisomy for some or all regions of chromosome 13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12393964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Patau syndrome is a chromosomal disorder associated with multiple malformations caused by inheritance of an extra chromosome (trisomy 13).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20537076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Survival of trisomy 18 (Edwards syndrome) and trisomy 13 (Patau Syndrome) in England and Wales: 2004-2011", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23949924", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 640, "text": "To determine whether older paternal age increases the risk of fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter (XXY) or XYY syndrome.Case-control: cases with each of these syndromes were matched to four controls with Down syndrome from within the same congenital anomaly register and with maternal age within 6 months.Data from 22 EUROCAT congenital anomaly registers in 12 European countries.Diagnoses with observed or (for terminations) predicted year of birth from 1980 to 2005, comprising live births, fetal deaths with gestational age \u2265 20 weeks and terminations after prenatal diagnosis of the anomaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20584846", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Congenital diaphragmatic hernia (CDH) occurs in 5-10% associated with chromosomal abnormalities like, Pallister Killian syndrome, Trisomy 18, and certain deletions.. Association of CDH with trisomy 13 (Patau syndromes) is very rare", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26034714", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 250, "text": "WHS is caused by a deletion of 4p16, while Patau syndrome is caused by trisomy for some or all regions of chromosome 13. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12393964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Patau syndrome is a chromosomal disorder associated with multiple malformations caused by inheritance of an extra chromosome (trisomy 13). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20537076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Ocular abnormalities in Patau syndrome (chromosome 13 trisomy syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2348978", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Trisomy 13 (Patau's syndrome): a rare case of survival into adulthood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2325123", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "BACKGROUND: Whilst maternal age is an established risk factor for Patau syndrome (trisomy 13), Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), the aetiology and contribution of genetic and environmental factors remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467377", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 249, "text": "WHS is caused by a deletion of 4p16, while Patau syndrome is caused by trisomy for some or all regions of chromosome 13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12393964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Patau syndrome, trisomy 13, is the third commonest autosomal trisomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25459971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Patau syndrome (trisomy 13) is very rare in live-born babies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17603803", "endSection": "abstract" } ] }, { "body": "Which is the main abnormality that arises with Sox9 locus duplication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "http://www.ncbi.nlm.nih.gov/pubmed/18391513", "http://www.ncbi.nlm.nih.gov/pubmed/22678921", "http://www.ncbi.nlm.nih.gov/pubmed/25010117", "http://www.ncbi.nlm.nih.gov/pubmed/24040047", "http://www.ncbi.nlm.nih.gov/pubmed/25077096", "http://www.ncbi.nlm.nih.gov/pubmed/11420125", "http://www.ncbi.nlm.nih.gov/pubmed/18056774" ], "ideal_answer": [ "The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. A complex network of genes determines sex in mammals. Differentiation of testicular tissue in 46,XX individuals is seen either in XX males, the majority of them with SRY gene, or in individuals, usually SRY(-), with ovotesticular disorder of sex development (OT-DSD). SOX9 is one of the genes that play critical roles in male sexual differentiation.", "Thus, SOX9 duplication is the most likely cause for the sex reversal in this case because it plays an important role in male sex determination and differentiation. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY.", "Autosomal XX sex reversal caused by duplication of SOX9. Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal. We report here evidence supporting that SOX9 duplication can cause XX sex reversal. Fluorescent in situ hybridization (FISH) with a BAC clone containing the SOX9 gene demonstrated that the SOX9 gene is duplicated on the rearranged chromosome 17. SOX9 duplication linked to intersex in deer. ", "SOX9 duplication can cause XX sex reversal. SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans.", "Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans.", "Autosomal XX sex reversal caused by duplication of SOX9" ], "exact_answer": [ "Autosomal XX sex reversal" ], "type": "factoid", "id": "58af1cb3717cd3f655000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Autosomal XX sex reversal caused by duplication of SOX9", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "endSection": "title" }, { "offsetInBeginSection": 82, "offsetInEndSection": 180, "text": "Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 264, "text": "We report here evidence supporting that SOX9 duplication can cause XX sex reversal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 691, "text": "Fluorescent in situ hybridization (FISH) with a BAC clone containing the SOX9 gene demonstrated that the SOX9 gene is duplicated on the rearranged chromosome 17", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "SOX9 duplication linked to intersex in deer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040047", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 358, "text": "Whole genome sequencing and quantitative real-time PCR analyses revealed a triple dose of the SOX9 gene, allowing insights into a new genetic defect in a wild animal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040047", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 672, "text": "In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25077096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18391513", "endSection": "title" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1307, "text": "Together, these findings implicate a mutation at a sex-determining locus other than SRY and SOX9 as the cause for the XX sex reversal trait in this family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18391513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Autosomal XX sex reversal caused by duplication of SOX9.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Sox9 duplications are a relevant cause of Sry-negative XX sex reversal dogs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25010117", "endSection": "title" }, { "offsetInBeginSection": 182, "offsetInEndSection": 265, "text": "We report here evidence supporting that SOX9 duplication can cause XX sex reversal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 181, "text": "Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10588843", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1081, "text": "Duplications of the locus DSS can lead to a failure of testicular development and a duplication of the region containing SOX9 has been implicated in XX sex reversal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11420125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18391513", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22678921", "endSection": "title" } ] }, { "body": "Is Musclin a secretory peptide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17189616", "http://www.ncbi.nlm.nih.gov/pubmed/17950246", "http://www.ncbi.nlm.nih.gov/pubmed/19244276", "http://www.ncbi.nlm.nih.gov/pubmed/23940802", "http://www.ncbi.nlm.nih.gov/pubmed/24734231", "http://www.ncbi.nlm.nih.gov/pubmed/26449458" ], "ideal_answer": [ "Yes, musclin has been described as a muscle-derived secretory peptide." ], "exact_answer": "yes", "type": "yesno", "id": "58df779d6fddd3e83e000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Musclin is a novel skeletal muscle-derived secretory factor,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17950246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Musclin has been described as a muscle-derived secretory peptide, responsive to insulin in vivo, and inducing insulin resistance in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17189616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Musclin is a type of muscle-secreted cytokine and its increased gene expression induces insulin resistance in type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26449458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Musclin is a novel skeletal muscle-derived factor found in the signal sequence trap of mouse skeletal muscle cDNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24734231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Musclin is a novel skeletal muscle-derived secretory factor found in the signal sequence trap of mouse skeletal muscle cDNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Musclin is a novel skeletal muscle-derived secretory factor that was isolated by our group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19244276", "endSection": "abstract" } ] }, { "body": "What tissue is commonly affected in Marfan's syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23304566", "http://www.ncbi.nlm.nih.gov/pubmed/26494287", "http://www.ncbi.nlm.nih.gov/pubmed/21723458", "http://www.ncbi.nlm.nih.gov/pubmed/21308160", "http://www.ncbi.nlm.nih.gov/pubmed/26281765", "http://www.ncbi.nlm.nih.gov/pubmed/26272787", "http://www.ncbi.nlm.nih.gov/pubmed/16400220", "http://www.ncbi.nlm.nih.gov/pubmed/14304236", "http://www.ncbi.nlm.nih.gov/pubmed/9401003", "http://www.ncbi.nlm.nih.gov/pubmed/19554831", "http://www.ncbi.nlm.nih.gov/pubmed/8240311", "http://www.ncbi.nlm.nih.gov/pubmed/21866385", "http://www.ncbi.nlm.nih.gov/pubmed/9068910", "http://www.ncbi.nlm.nih.gov/pubmed/9316048", "http://www.ncbi.nlm.nih.gov/pubmed/17620463", "http://www.ncbi.nlm.nih.gov/pubmed/10050736" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0024796", "o": "Marfan Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0024796", "o": "http://linkedlifedata.com/resource/umls/label/A0431931" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0431931", "o": "MARFAN SYNDROME" } ], "ideal_answer": [ "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents ", "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents", "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents. ", "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents.", "marfan syndrome (ms) is a connective tissue disorder that affects thousands of adolescents ." ], "exact_answer": [ "connective tissue" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382", "http://www.disease-ontology.org/api/metadata/DOID:14323" ], "type": "factoid", "id": "58dd0dde8acda34529000027", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26272787", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 636, "text": "Fibrillin-1 mutations have also been found in several other related connective tissue disorders, such as severe neonatal Marfan syndrome, dominant ectopia lentis, familial ascending aortic aneurysm, isolated skeletal features of Marfan syndrome, and Shprintzen-Goldberg syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Marfans syndrome is an Autosomal dominant disorder of the connective tissues resulting in abnormalities of the musculoskeletal system, cardiovascular system and eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16400220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Marfan syndrome (MFS) is a systemic disorder of the connective tissue with pleiotropic manifestations due to heterozygous FBN1 mutations and consequent upregulation of TGF\u03b2 signaling in affected tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21866385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, caused by mutations of the microfibrillar protein fibrillin-1, that predisposes affected individuals to aortic aneurysm and rupture and is associated with increased TGF\u03b2 signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26494287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Marfan syndrome is an autosomal dominant connective tissue disorder commonly due to mutation of the fibrillin-1 (FBN-1) gene that causes disruption of elastic fibers in large- and medium-size arteries and predisposes to aneurysm formation and arterial dissection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21723458", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 236, "text": "Children affected by the Marfan syndrome carry a mutation in one of their two copies of the gene that encodes the connective tissue protein fibrillin-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23304566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Marfan's syndrome is an autosomal dominant disorder of connective tissue, commonly involving the cardiovascular, ocular, and skeletal systems. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10050736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Marfan syndrome is an autosomal dominant connective tissue disorder commonly due to mutation of the fibrillin-1 (FBN-1) gene that causes disruption of elastic fibers in large- and medium-size arteries and predisposes to aneurysm formation and arterial dissection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21723458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Marfan's syndrome is an autosomal dominant disorder of connective tissue, commonly involving the cardiovascular, ocular, and skeletal systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10050736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Marfan's syndrome is a heritable connective tissue disorder that has been associated with intracranial aneurysms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9316048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Marfan's syndrome is an inherited disorder of connective tissue associated with characteristic abnormalities of the skeletal, ocular, and cardiovascular systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9068910", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 939, "text": "Therefore, Marfan's syndrome is termed a fibrillinopathy, along with other connective tissue disorders with subtle differences in clinical manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21308160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The Marfan syndrome is an inherited disorder of the connective tissue which is mainly caused by a mutation in the fibrillin-1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19554831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Marfan syndrome is an inherited multisystemic connective-tissue disease that is caused by a mutation of the fibrillin-1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17620463", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 497, "text": " Mutations in the fibrillin-1 gene give rise to Marfan syndrome, a connective tissue disorder with clinical complications in the cardiovascular, skeletal, ocular and other organ systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26281765", "endSection": "abstract" } ] }, { "body": "To which disease does the loss of CD28 expression by liver-infiltrating T cells contribute?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24726754" ], "ideal_answer": [ "Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis.", "Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis. ", "loss of cd28 expression by liver-infiltrating t cells contributes to pathogenesis of primary sclerosing cholangitis." ], "exact_answer": [ "Primary sclerosing cholangitis" ], "concepts": [ "http://www.uniprot.org/uniprot/CD28_RABIT", "http://www.uniprot.org/uniprot/CD28_RAT", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008107", "http://www.uniprot.org/uniprot/CD28_HUMAN", "http://www.uniprot.org/uniprot/CD28_CHICK", "http://www.uniprot.org/uniprot/CD28_FELCA", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058625", "http://www.uniprot.org/uniprot/CD28_BOVIN", "http://www.uniprot.org/uniprot/CD28_MOUSE" ], "type": "factoid", "id": "58853922e56acf5176000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24726754", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24726754", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24726754", "endSection": "title" } ] }, { "body": "Are cutaneous porphyrias inherited with a recessive pattern?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15868463", "http://www.ncbi.nlm.nih.gov/pubmed/11202049", "http://www.ncbi.nlm.nih.gov/pubmed/12859407" ], "ideal_answer": [ "No, cutaneous porphyrias are inherited in a dominant (not recessive) pattern." ], "exact_answer": "no", "type": "yesno", "id": "58e11b9b6fddd3e83e00000b", "snippets": [ { "offsetInBeginSection": 464, "offsetInEndSection": 728, "text": "Five of the porphyrias are low-penetrance autosomal dominant conditions in which clinical expression results from additional factors that act by increasing demand for haem or by causing an additional decrease in enzyme activity or by a combination of these effects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15868463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Molecular mechanisms of dominant expression in porphyria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15868463", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12859407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The acute porphyrias constitute a group of metabolic disorders engaging enzymes in the haem synthetic chain and generally following dominant inheritance patterns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11202049", "endSection": "abstract" } ] }, { "body": "Which disease is treated with ZMapp?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25694097", "http://www.ncbi.nlm.nih.gov/pubmed/25352204", "http://www.ncbi.nlm.nih.gov/pubmed/30053153", "http://www.ncbi.nlm.nih.gov/pubmed/29688496", "http://www.ncbi.nlm.nih.gov/pubmed/27274814", "http://www.ncbi.nlm.nih.gov/pubmed/26311869", "http://www.ncbi.nlm.nih.gov/pubmed/25404321", "http://www.ncbi.nlm.nih.gov/pubmed/26962157", "http://www.ncbi.nlm.nih.gov/pubmed/27279622", "http://www.ncbi.nlm.nih.gov/pubmed/29736037", "http://www.ncbi.nlm.nih.gov/pubmed/27067649", "http://www.ncbi.nlm.nih.gov/pubmed/26798032", "http://www.ncbi.nlm.nih.gov/pubmed/26861827", "http://www.ncbi.nlm.nih.gov/pubmed/27683818", "http://www.ncbi.nlm.nih.gov/pubmed/29179602", "http://www.ncbi.nlm.nih.gov/pubmed/25465382", "http://www.ncbi.nlm.nih.gov/pubmed/26191408", "http://www.ncbi.nlm.nih.gov/pubmed/26946569", "http://www.ncbi.nlm.nih.gov/pubmed/25414384", "http://www.ncbi.nlm.nih.gov/pubmed/27521366", "http://www.ncbi.nlm.nih.gov/pubmed/25760722", "http://www.ncbi.nlm.nih.gov/pubmed/28073857", "http://www.ncbi.nlm.nih.gov/pubmed/25171469", "http://www.ncbi.nlm.nih.gov/pubmed/27637475", "http://www.ncbi.nlm.nih.gov/pubmed/25648233", "http://www.ncbi.nlm.nih.gov/pubmed/27676206", "http://www.ncbi.nlm.nih.gov/pubmed/25260583", "http://www.ncbi.nlm.nih.gov/pubmed/27465308", "http://www.ncbi.nlm.nih.gov/pubmed/25387576", "http://www.ncbi.nlm.nih.gov/pubmed/28357917", "http://www.ncbi.nlm.nih.gov/pubmed/25648530", "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "http://www.ncbi.nlm.nih.gov/pubmed/27959624" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0049608" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "Disease" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/1022004", "o": "http://linkedlifedata.com/resource/rxnorm/label/3147522" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3147522", "o": "Disease" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A18683747" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18683747", "o": "disease" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0015569" } ], "ideal_answer": [ "ZMapp is a combination of antibodies for treatment of Ebola virus disease.", "Vectored delivery of the ZMapp antibody cocktail (c2G4, c4G7, and c13C6) by using recombinant adeno-associated viruses (rAAVs) is useful for preventive immunization against Ebola virus infection." ], "exact_answer": [ "Ebola virus disease", "Ebola virus infection" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category" ], "type": "factoid", "id": "5880e417713cbdfd3d000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Gene Transfer of ZMapp Antibodies Mediated by Recombinant Adeno-Associated Virus Protects Against Ebola Infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29179602", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Vectored delivery of the ZMapp antibody cocktail (c2G4, c4G7, and c13C6) by using recombinant adeno-associated viruses (rAAVs) could be useful for preventive immunization against Ebola virus infections because rAAVs can generate long-term antibody expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29179602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "ZMapp Reinforces the Airway Mucosal Barrier Against Ebola Virus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688496", "endSection": "title" }, { "offsetInBeginSection": 641, "offsetInEndSection": 901, "text": "Addition of ZMapp, a cocktail of Ebola-binding immunoglobulin G antibodies, effectively reduced mobility of Ebola pseudovirus in the same mucus secretions. Topical delivery of ZMapp to the mouse airways also facilitated rapid elimination of Ebola pseudovirus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688496", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 344, "text": "Several strategies have been developed in the past to treat EBOV infection, including the antibody cocktail ZMapp, which has been shown to be effective in nonhuman primate models of infection 1 and has been used under compassionate-treatment protocols in humans 2 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29736037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Antibody therapy has been used to treat a variety of diseases and the success of ZMapp and other monoclonal antibody-based therapies during the 2014-2016 West African Ebola outbreak has shown this countermeasure can be a successful therapy for Ebola hemorrhagic fever. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053153", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 383, "text": "Only recently have vaccine or drug regimens for the Ebola virus been developed, including Zmapp and peptides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27637475", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 596, "text": "Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid-based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27959624", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 265, "text": " The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28073857", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 580, "text": "However, during the recent outbreak, monoclonal antibody cocktails such as ZMapp, ZMAb and MB-003 were either tested in a human clinical safety and efficacy trial or provided to some based on compassionate grounds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28357917", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1902, "text": "Cocktails of inhibitory monoclonal antibodies (MAbs), such as ZMAb, MB-003, and in particular ZMapp, have demonstrated in animal models some of the most significant therapeutic potential for treating EVD, and in 2014, 15 patients were treated with ZMapp or ZMAb under compassionate-use protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26311869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND\n\nData from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 381, "text": "For example, several patients of the present Ebola virus outbreak in West Africa were treated with ZMapp, a cocktail of three monoclonal antibodies which are expressed in Nicotiana benthamiana.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26191408", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 265, "text": "The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28073857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease ( EVD ) .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Several patients with Ebola virus disease ( EVD ) managed in the United States have received ZMapp monoclonal antibodies , TKM-Ebola small interfering RNA , brincidofovir , and/or convalescent plasma as investigational therapeutics .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND\nData from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 449, "text": "METHODS\nBeginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 433, "text": "During the 2014 Ebola outbreak, an experimental drug named ZMapp was administered on an emergency basis to seven patients of which five were recovered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26946569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861827", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 691, "text": "This includes agents belonging to various therapeutic classes, namely direct antiviral agents (favipiravir and BCX4430), a combination of antibodies (ZMapp), type I interferons, RNA interference-based drugs (TKM-Ebola and AVI-7537), and anticoagulant drugs (rNAPc2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26798032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27067649", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 708, "text": "The human-mouse chimeric monoclonal antibody (mAb) cocktail ZMapp, previously shown to be efficacious in EBOV (variant Kikwit) lethally infected nonhuman primates (NHPs) when administration was initiated up to 5 days, was used in some patients during the outbreak. We show that a two-antibody cocktail, MIL77E, is fully protective in NHPs when administered at 50 mg/kg 3 days after challenge with a lethal dose of EBOV variant Makona, the virus responsible for the ongoing 2014-2015 outbreak, whereas a similar formulation of ZMapp protected two of three NHPs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26962157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The growing promise of plant-made biologics is highlighted by the success story of ZMapp\u2122 as a potentially life-saving drug during the Ebola outbreak of 2014-2016. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27274814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25171469", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Background Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Several patients with Ebola virus disease (EVD) managed in the United States have received ZMapp monoclonal antibodies, TKM-Ebola small interfering RNA, brincidofovir, and/or convalescent plasma as investigational therapeutics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521366", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 838, "text": "Also there is no specific vaccine and treatment for Ebola virus; however, many candidate vaccines and antiviral-drugs such as ZMapp and TKM-Ebola are being developed for Ebola virus disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25648530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732819", "endSection": "title" }, { "offsetInBeginSection": 757, "offsetInEndSection": 869, "text": "ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25171469", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1489, "text": "Going forward, this work now provides a basis for strategic selection of next-generation antibody cocktails against Ebola and related viruses and a model for predicting the impact of ZMapp on potential escape mutations in ongoing or future Ebola outbreaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404321", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 742, "text": "Some potential therapeutic materials including ZMapp were supplied and the treated people got over the EVD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25648233", "endSection": "abstract" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1876, "text": "Cocktails of inhibitory monoclonal antibodies (MAbs), such as ZMAb, MB-003, and in particular ZMapp, have demonstrated in animal models some of the most significant therapeutic potential for treating EVD, and in 2014, 15 patients were treated with ZMapp or ZMAb under compassionate-use protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26311869", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 666, "text": "This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25465382", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 868, "text": "ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25171469", "endSection": "abstract" }, { "offsetInBeginSection": 1581, "offsetInEndSection": 1877, "text": "Cocktails of inhibitory monoclonal antibodies (MAbs), such as ZMAb, MB-003, and in particular ZMapp, have demonstrated in animal models some of the most significant therapeutic potential for treating EVD, and in 2014, 15 patients were treated with ZMapp or ZMAb under compassionate-use protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26311869", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 369, "text": "For example, several patients of the present Ebola virus outbreak in West Africa were treated with ZMapp, a cocktail of three monoclonal antibodies which are expressed in Nicotiana benthamiana.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26191408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25171469", "endSection": "title" } ] }, { "body": "Can methylenetetrahydrofolate reductase (MTHFR) gene mutations cause homocystinuria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16629766", "http://www.ncbi.nlm.nih.gov/pubmed/27130656", "http://www.ncbi.nlm.nih.gov/pubmed/10980581", "http://www.ncbi.nlm.nih.gov/pubmed/23095199", "http://www.ncbi.nlm.nih.gov/pubmed/10923034", "http://www.ncbi.nlm.nih.gov/pubmed/21626167", "http://www.ncbi.nlm.nih.gov/pubmed/2629632", "http://www.ncbi.nlm.nih.gov/pubmed/17457696", "http://www.ncbi.nlm.nih.gov/pubmed/12673793", "http://www.ncbi.nlm.nih.gov/pubmed/11592438", "http://www.ncbi.nlm.nih.gov/pubmed/9490685", "http://www.ncbi.nlm.nih.gov/pubmed/23533858", "http://www.ncbi.nlm.nih.gov/pubmed/20532821", "http://www.ncbi.nlm.nih.gov/pubmed/9453374", "http://www.ncbi.nlm.nih.gov/pubmed/10679944", "http://www.ncbi.nlm.nih.gov/pubmed/24461181", "http://www.ncbi.nlm.nih.gov/pubmed/14656017", "http://www.ncbi.nlm.nih.gov/pubmed/20236116", "http://www.ncbi.nlm.nih.gov/pubmed/22521626", "http://www.ncbi.nlm.nih.gov/pubmed/9781030", "http://www.ncbi.nlm.nih.gov/pubmed/11181567", "http://www.ncbi.nlm.nih.gov/pubmed/17349292", "http://www.ncbi.nlm.nih.gov/pubmed/8124871" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0066357", "o": "MTHFR" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5034323839380027", "o": "MTHFR" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5135534E573500F", "o": "MTHFR" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/drugbank/molecule/3917", "o": "Methylenetetrahydrofolate reductase" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://linkedlifedata.com/resource/drugbank/molecule/3917", "o": "http://purl.uniprot.org/uniprot/P42898" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/uniprot/P42898", "o": "MTHR_HUMAN" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/uniprot/P42898", "o": "http://purl.uniprot.org/uniprot/P42898" } ], "ideal_answer": [ "Yes, several methylenetetrahydrofolate reductase (MTHFR) gene mutations can cause homocystinuria and hyperhomocysteinemia." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/MTHR_MOUSE", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006712", "http://www.uniprot.org/uniprot/MTHR_BOVIN", "http://www.disease-ontology.org/api/metadata/DOID:9263", "http://www.uniprot.org/uniprot/MTHR_MACFA", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/MTHR_HUMAN" ], "type": "yesno", "id": "58d8d0cc8acda34529000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24461181", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 391, "text": "Several mutations seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of hyperhomocysteinemia and homocystinuria, a considerable risk factor for cardiovascular and cerebrovascular disorders, by leading to enzymatic inactivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23533858", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 764, "text": "At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24461181", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 814, "text": "Response to treatment demonstrated B(6)-non-responsive homocystinuria. Molecular study showed compound heterozygous T353\u00a0N and D444\u00a0N mutations of the cystathionine beta-synthase (CBS) gene, and also a C667T homozygous mutation of the methylenetetrahydrofolate-reductase (MTHFR) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21626167", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1374, "text": "Our case is atypical because of the absence of thromboembolism and the mild phenotype, in spite of being B(6)-non-responsive, and the association of a rare compound heterozygous mutation of the CBS gene and also an homozygous mutation of the MTHFR gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21626167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20236116", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17349292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the regulation of plasma homocysteine levels. MTHFR deficiency, an autosomal recessive disorder, results in homocystinuria and hypomethioninaemia and presents with highly variable symptoms affecting many organs but predominantly the central nervous system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17457696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16629766", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 431, "text": "Rare mutations in the MTHFR gene have been associated with autosomal recessive MTHFR deficiency leading to homocystinuria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27130656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10679944", "endSection": "title" }, { "offsetInBeginSection": 227, "offsetInEndSection": 414, "text": "Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20236116", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1417, "text": "The results of our study render the full-length characterisation of affected alleles in severe homocystinuria and moderate hyperhomocysteinaemia due to MTHFR deficiency and provide a basis for investigating the regulation of the human MTHFR gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10980581", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 455, "text": "Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17349292", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 385, "text": "Different MTHFR mutations lead either to severe homocystinuria as a multisystem disorder or to moderate hyperhomocysteinaemia, which is a common risk factor for disorders ranging from cardiovasculopathy to spina bifida.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10980581", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 712, "text": "We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490685", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1094, "text": "On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490685", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 715, "text": "We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16629766", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 714, "text": "We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10679944", "endSection": "title" }, { "offsetInBeginSection": 144, "offsetInEndSection": 278, "text": "The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11181567", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 444, "text": "The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11592438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095199", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 403, "text": "The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14656017", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 716, "text": "We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "AIM: Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16629766", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Betaine for treatment of homocystinuria caused by methylenetetrahydrofolate reductase deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2629632", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) with homocystinuria can result in early demise or later-onset neurological impairment, including developmental delay, motor dysfunction, and seizures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20532821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) leads to deficient remethylation of homocysteine and is one of the causes of homocystinuria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8124871", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 369, "text": "Neurological disturbances have been described in homocystinuria caused by severe MTHFR deficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22521626", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 445, "text": "The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11592438", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 261, "text": "Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17349292", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 404, "text": "The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14656017", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 279, "text": "The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11181567", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 457, "text": "Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17349292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10679944", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20236116", "endSection": "title" }, { "offsetInBeginSection": 812, "offsetInEndSection": 1099, "text": "On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490685", "endSection": "abstract" } ] }, { "body": "What happens to H2AX upon DNA bouble strand breaks?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22704343", "http://www.ncbi.nlm.nih.gov/pubmed/27158526", "http://www.ncbi.nlm.nih.gov/pubmed/24682951", "http://www.ncbi.nlm.nih.gov/pubmed/21511815" ], "ideal_answer": [ " Phosphorylated H2AX (\u03b3H2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress The nuclear foci of phosphorylated histone H2AX (\u03b3H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR)", " phosphorylated h2ax (\u03b3h2ax) is rapidly concentrated in chromatin domains around dna double-strand breaks (dsbs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress.", "Defective or inefficient DNA double-strand break (DSB) repair results in failure to preserve genomic integrity leading to apoptotic cell death, a hallmark of systemic lupus erythematosus (SLE). Phosphorylated H2AX (\u00ce\u00b3H2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress.", "The nuclear foci of phosphorylated histone H2AX (\u03b3H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR). Phosphorylated H2AX (\u03b3H2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress. DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin", "Histone H2AX phosphorylation as a measure of DNA double-strand breaks and a marker of environmental stress and disease activity in lupus. DSBs were quantified in peripheral blood mononuclear cell subsets from patients with SLE, healthy controls, and patients with rheumatoid arthritis (RA) by measuring phosphorylated H2AX (phospho-H2AX) levels with flow cytometry. Most hydrogen peroxide-induced histone H2AX phosphorylation is mediated by ATR and is not dependent on DNA double-strand breaks. The nuclear foci of phosphorylated histone H2AX (H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR). These results suggest that a major fraction of H2AX induced by oxidative stress is not associated with DSBs. ", "Defective or inefficient DNA double-strand break (DSB) repair results in failure to preserve genomic integrity leading to apoptotic cell death, a hallmark of systemic lupus erythematosus (SLE). The nuclear foci of phosphorylated histone H2AX (\u03b3H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR). A sequence variant of histone H2A called H2AX is one of the key components of chromatin involved in DNA damage response induced by different genotoxic stresses. DNA double-strand breaks (DSBs) can induce chromosomal aberrations and carcinogenesis and their correct repair is crucial for genetic stability.", "DSBs were quantified in peripheral blood mononuclear cell subsets from patients with SLE, healthy controls, and patients with rheumatoid arthritis (RA) by measuring phosphorylated H2AX (phospho-H2AX) levels with flow cytometry DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin" ], "exact_answer": [ "it is rapidly concentrated" ], "type": "factoid", "id": "58af16ea717cd3f655000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Histone H2AX phosphorylation as a measure of DNA double-strand breaks and a marker of environmental stress and disease activity in lupus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27158526", "endSection": "title" }, { "offsetInBeginSection": 542, "offsetInEndSection": 768, "text": "DSBs were quantified in peripheral blood mononuclear cell subsets from patients with SLE, healthy controls, and patients with rheumatoid arthritis (RA) by measuring phosphorylated H2AX (phospho-H2AX) levels with flow cytometry", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27158526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Most hydrogen peroxide-induced histone H2AX phosphorylation is mediated by ATR and is not dependent on DNA double-strand breaks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682951", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The nuclear foci of phosphorylated histone H2AX (\u03b3H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682951", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1243, "text": "These results suggest that a major fraction of \u03b3H2AX induced by oxidative stress is not associated with DSBs. Single-stranded DNA arisen from stalled replication forks can cause the ATR-mediated induction of \u03b3H2AX", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24682951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704343", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "A sequence variant of histone H2A called H2AX is one of the key components of chromatin involved in DNA damage response induced by different genotoxic stresses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704343", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 389, "text": " Phosphorylated H2AX (\u03b3H2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21511815", "endSection": "title" }, { "offsetInBeginSection": 146, "offsetInEndSection": 583, "text": "he cellular response to DSBs depends on damage signaling including the phosphorylation of the histone H2AX (\u03b3H2AX). However, a lack of \u03b3H2AX formation in heterochromatin (HC) is generally observed after DNA damage induction. Here, we examine \u03b3H2AX and repair protein foci along linear ion tracks traversing heterochromatic regions in human or murine cells and find the DSBs and damage signal streaks bending around highly compacted DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21511815", "endSection": "abstract" } ] }, { "body": "Can valproic acid prolong survival of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26786929", "http://www.ncbi.nlm.nih.gov/pubmed/26976976", "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "http://www.ncbi.nlm.nih.gov/pubmed/26925628", "http://www.ncbi.nlm.nih.gov/pubmed/22168970", "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "http://www.ncbi.nlm.nih.gov/pubmed/26420896", "http://www.ncbi.nlm.nih.gov/pubmed/25648357", "http://www.ncbi.nlm.nih.gov/pubmed/18751431", "http://www.ncbi.nlm.nih.gov/pubmed/27889835", "http://www.ncbi.nlm.nih.gov/pubmed/24328881", "http://www.ncbi.nlm.nih.gov/pubmed/23523186" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0042291", "o": "valproic acid" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0042291", "o": "http://linkedlifedata.com/resource/umls/label/A10769673" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10769673", "o": "VALPROIC ACID" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/11118", "o": "http://linkedlifedata.com/resource/rxnorm/label/3253230" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3253230", "o": "VALPROIC ACID" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0042291", "o": "http://linkedlifedata.com/resource/umls/label/A0131324" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0131324", "o": "Valproic Acid" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/11118", "o": "http://linkedlifedata.com/resource/rxnorm/label/3254597" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3254597", "o": "Valproic Acid" } ], "ideal_answer": [ "Yes, there is evidence to suggest that valproic acid (VPA) is associated with prolonged survival of glioblastoma patients. Several studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016019", "http://www.disease-ontology.org/api/metadata/DOID:3073", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.biosemantics.org/jochem#4271063", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005909", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4271063", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015996", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013534", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014635" ], "type": "yesno", "id": "5884755ce56acf5176000007", "snippets": [ { "offsetInBeginSection": 978, "offsetInEndSection": 1152, "text": "For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26420896", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1372, "text": "This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26420896", "endSection": "abstract" }, { "offsetInBeginSection": 571, "offsetInEndSection": 1042, "text": "Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26925628", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 368, "text": "While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25648357", "endSection": "abstract" }, { "offsetInBeginSection": 1851, "offsetInEndSection": 1955, "text": " Additionally, VPA may result in improved outcomes compared to historical data and merits further study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1247, "text": "Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24328881", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 335, "text": "Several clinical studies have reported that valproic acid could prolong survival of GBM patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 367, "text": "While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25648357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Valproic acid use during radiation therapy for glioblastoma associated with improved survival.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523186", "endSection": "title" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1333, "text": "Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1249, "text": "Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24328881", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 740, "text": "Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma.To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26786929", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 336, "text": "Several clinical studies have reported that valproic acid could prolong survival of GBM patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1420, "text": "Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 537, "text": "The combination of radiotherapy, temozolomide and valproic acid (VPA) has shown some promise in retrospective analyses of patients with glioblastoma, although their mechanisms of action remain unknown.We investigated the in vitro and in vivo effects of pretreating glioma cells with temozolomide and VPA as an immunization strategy to boost an adaptive immune response in a syngeneic mouse model.Temozolomide and VPA induced autophagy in GL261 glioma cells, and caused tumor antigen-specific T-cells to become activated effector T-cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26976976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "endSection": "title" } ] }, { "body": "What is the effect of the direct interaction of Ikaros and Foxp1 in B-lymphocytes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27588474" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1825588", "o": "http://linkedlifedata.com/resource/umls/label/A20756491" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20756491", "o": "IKAROS" } ], "ideal_answer": [ "Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia.", "The effect of the direct interaction of Ikaros and Foxp1 in B-lymphocytesis is modulation of expression of the G protein-coupled receptor G2A." ], "exact_answer": [ "Modulation of expression of the G protein-coupled receptor G2A." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001402", "http://www.uniprot.org/uniprot/FOXP1_RAT", "http://www.uniprot.org/uniprot/FOXP1_MOUSE", "http://www.biosemantics.org/jochem#4250484", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060151", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051740" ], "type": "factoid", "id": "58853667e56acf5176000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27588474", "endSection": "title" }, { "offsetInBeginSection": 114, "offsetInEndSection": 555, "text": "We describe a novel physical and functional interaction between the proteins, which requires the central zinc finger domain of Ikaros. The Ikaros-Foxp1 interaction is abolished by deletion of this region, which corresponds to the IK6 isoform that is commonly associated with high-risk acute lymphoblastic leukemia (ALL). We also identify the Gpr132 gene, which encodes the orphan G protein-coupled receptor G2A, as a novel target for Foxp1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27588474", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1216, "text": "Our results reveal a novel effect of Ikaros haploinsufficiency on Foxp1 functioning, and identify G2A as a potential modulator of the cell cycle in Ikaros-deleted B-ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27588474", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1209, "text": "Our results reveal a novel effect of Ikaros haploinsufficiency on Foxp1 functioning, and identify G2A as a potential modulator of the cell cycle in Ikaros-deleted B-ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27588474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27588474", "endSection": "title" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1217, "text": "Our results reveal a novel effect of Ikaros haploinsufficiency on Foxp1 functioning, and identify G2A as a potential modulator of the cell cycle in Ikaros-deleted B-ALL..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27588474", "endSection": "abstract" } ] }, { "body": "Which syndrome is caused by deletion of Pds5b in mice?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17652350", "http://www.ncbi.nlm.nih.gov/pubmed/19412548" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1442161", "o": "Gene Deletion" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0039082", "o": "Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0039082", "o": "http://linkedlifedata.com/resource/umls/label/A0121946" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0121946", "o": "Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/989712", "o": "http://linkedlifedata.com/resource/rxnorm/label/3242053" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3242053", "o": "Syndrome" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1511760", "o": "Deletion" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1442161", "o": "http://linkedlifedata.com/resource/umls/label/A10802767" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10802767", "o": "Deletion" } ], "ideal_answer": [ "Mice lacking sister chromatid cohesion protein Pds5b exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome.", "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome. ", "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome.", "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome", "mice lacking sister chromatid cohesion protein pds5b exhibit developmental abnormalities reminiscent of cornelia de lange syndrome." ], "exact_answer": [ "Cornelia de Lange syndrome." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0090695", "http://www.uniprot.org/uniprot/PDS5B_RAT", "http://www.uniprot.org/uniprot/PDS5B_MOUSE" ], "type": "factoid", "id": "5889eb503b87a8a73800000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652350", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 364, "text": "Pds5B mutant mice have developmental abnormalities resembling CdLS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652350", "endSection": "title" }, { "offsetInBeginSection": 296, "offsetInEndSection": 460, "text": "Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412548", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 462, "text": "Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652350", "endSection": "title" } ] }, { "body": "What is the inheritance of Barth syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9345098", "http://www.ncbi.nlm.nih.gov/pubmed/21932011", "http://www.ncbi.nlm.nih.gov/pubmed/12749056", "http://www.ncbi.nlm.nih.gov/pubmed/16847078", "http://www.ncbi.nlm.nih.gov/pubmed/24751896", "http://www.ncbi.nlm.nih.gov/pubmed/24342716", "http://www.ncbi.nlm.nih.gov/pubmed/24093814", "http://www.ncbi.nlm.nih.gov/pubmed/21068380", "http://www.ncbi.nlm.nih.gov/pubmed/8884581", "http://www.ncbi.nlm.nih.gov/pubmed/11975944", "http://www.ncbi.nlm.nih.gov/pubmed/12112112", "http://www.ncbi.nlm.nih.gov/pubmed/16857210", "http://www.ncbi.nlm.nih.gov/pubmed/21987083", "http://www.ncbi.nlm.nih.gov/pubmed/23523468", "http://www.ncbi.nlm.nih.gov/pubmed/23031367", "http://www.ncbi.nlm.nih.gov/pubmed/8487269", "http://www.ncbi.nlm.nih.gov/pubmed/25185984", "http://www.ncbi.nlm.nih.gov/pubmed/8434619", "http://www.ncbi.nlm.nih.gov/pubmed/17353728", "http://www.ncbi.nlm.nih.gov/pubmed/19037987", "http://www.ncbi.nlm.nih.gov/pubmed/25776009" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0574083", "o": "Barth Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0574083", "o": "http://linkedlifedata.com/resource/umls/label/A12001922" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12001922", "o": "BARTH SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1336578", "o": "http://linkedlifedata.com/resource/umls/label/A20801255" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20801255", "o": "Barth syndrome" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/137", "o": "Barth_syndrome" } ], "ideal_answer": [ "Barth syndrome (BTHS) has an X-linked recessive pattern of inheritance." ], "exact_answer": [ "X-linked recessive pattern of inheritance" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.disease-ontology.org/api/metadata/DOID:0050476", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056889" ], "type": "factoid", "id": "58d900428acda3452900000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Barth syndrome (BTHS) is an X-linked recessive disease primarily affecting males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25776009", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1097, "text": "The results of our study should not only be applicable to BTHS families, but also to families with other X-linked diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25776009", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 256, "text": "Barth syndrome, an X-linked disorder that is characterized by cardiomyopathy, neutropenia, skeletal myopathy, and growth delay, is caused by mutations in the taffazin gene at Xq28 that result in cardiolipin deficiency and abnormal mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847078", "endSection": "abstract" }, { "offsetInBeginSection": 2300, "offsetInEndSection": 2553, "text": "Barth syndrome should be considered when boys present with cardiomyopathy, especially when associated with increased left ventricular trabeculations, neutropenia, skeletal muscle weakness, or family history indicating an X-linked pattern of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847078", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 418, "text": "Mutations in the G4.5 gene result in a wide spectrum of severe infantile X-linked cardiomyopathic phenotypes including Barth syndrome with dilated cardiomyopathy and INVM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12749056", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 755, "text": "X-linked mode of inheritance is seen in Menkes disease, Barth syndrome, and in deficiencies of the E1 alpha subunit of the pyruvate dehydrogenase complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8884581", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 749, "text": "X-linked mode of inheritance is seen in Menkes disease, Barth syndrome, and in deficiencies of the E1 alpha subunit of the pyruvate dehydrogenase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8884581", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "OBJECTIVE: Barth syndrome is a rare, X-linked recessive disorder that affects only boys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17353728", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 236, "text": "Barth syndrome, an X-linked mitochondrial cardioskeletal myopathy, was diagnosed by genetic testing at autopsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19037987", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Barth syndrome is an X-linked cardiomyopathy with neutropenia and 3-methylglutaconic aciduria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9345098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Barth syndrome is an X-linked cardiac and skeletal mitochondrial myopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12112112", "endSection": "abstract" }, { "offsetInBeginSection": 2265, "offsetInEndSection": 2517, "text": "Barth syndrome should be considered when boys present with cardiomyopathy, especially when associated with increased left ventricular trabeculations, neutropenia, skeletal muscle weakness, or family history indicating an X-linked pattern of inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847078", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 753, "text": "X-linked mode of inheritance is seen in Menkes disease, Barth syndrome, and in deficiencies of the E1 alpha subunit of the pyruvate dehydrogenase complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8884581", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 685, "text": "Although the cardiomyopathy was familial in two siblings, two of three cases were female, ruling out Barth syndrome (with sex-linked recessive inheritance)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11975944", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Barth syndrome is an X-linked genetic disorder caused by mutations in the tafazzin (taz) gene and characterized by dilated cardiomyopathy, exercise intolerance, chronic fatigue, delayed growth, and neutropenia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21068380", "endSection": "abstract" }, { "offsetInBeginSection": 2265, "offsetInEndSection": 2518, "text": "Barth syndrome should be considered when boys present with cardiomyopathy, especially when associated with increased left ventricular trabeculations, neutropenia, skeletal muscle weakness, or family history indicating an X-linked pattern of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847078", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 754, "text": "X-linked mode of inheritance is seen in Menkes disease, Barth syndrome, and in deficiencies of the E1 alpha subunit of the pyruvate dehydrogenase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8884581", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 686, "text": "Although the cardiomyopathy was familial in two siblings, two of three cases were female, ruling out Barth syndrome (with sex-linked recessive inheritance).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11975944", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 687, "text": "Although the cardiomyopathy was familial in two siblings, two of three cases were female, ruling out Barth syndrome (with sex-linked recessive inheritance).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11975944", "endSection": "abstract" }, { "offsetInBeginSection": 2265, "offsetInEndSection": 2519, "text": "Barth syndrome should be considered when boys present with cardiomyopathy, especially when associated with increased left ventricular trabeculations, neutropenia, skeletal muscle weakness, or family history indicating an X-linked pattern of inheritance..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16847078", "endSection": "abstract" } ] }, { "body": "Is Cryptococcus neoformans a frequent cause of isolated skin infections in immunocompromised individuals", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26246081", "http://www.ncbi.nlm.nih.gov/pubmed/12602722", "http://www.ncbi.nlm.nih.gov/pubmed/27852678", "http://www.ncbi.nlm.nih.gov/pubmed/12219115" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0010414", "o": "http://linkedlifedata.com/resource/umls/label/A18683550" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18683550", "o": "cryptococcus neoformans" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0010416", "o": "Cryptococcus neoformans" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0010416", "o": "http://linkedlifedata.com/resource/umls/label/A0043970" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0010414", "o": "http://linkedlifedata.com/resource/umls/label/A8355137" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8355137", "o": "Infection by Cryptococcus neoformans" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0010414", "o": "http://linkedlifedata.com/resource/umls/label/A0560486" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0560486", "o": "Infection by Cryptococcus neoformans" } ], "ideal_answer": [ "Primary cutaneous cryptococcosis (PCC) without systemic infection is rare." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003453", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012874", "http://www.disease-ontology.org/api/metadata/DOID:12053", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003455", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003454" ], "type": "yesno", "id": "58e120036fddd3e83e00000d", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 284, "text": " Cryptococcus is an opportunistic yeast with a worldwide distribution that primarily causes significant infections in immunocompromised individuals, generally by affecting the respiratory tract. But primary cutaneous cryptococcosis (PCC) without systemic infection is rare. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26246081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Cryptococcus is a ubiquitous fungus and is known for causing meningitis and cutaneous infections in immunocompromised individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27852678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Cryptococcus neoformans is an encapsulated yeast that can cause primary pulmonary infections or disseminate and cause infections of the central nervous system, meninges, skin, and bone in the immunocompromised host.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12602722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The authors report a male patient, a seller with no detected immunosuppression, with an extensive ulcerated skin lesion localized on the left forearm, caused by Cryptococcus neoformans var.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12219115", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Pictilisib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27044711", "http://www.ncbi.nlm.nih.gov/pubmed/25370471", "http://www.ncbi.nlm.nih.gov/pubmed/27573562", "http://www.ncbi.nlm.nih.gov/pubmed/26830312", "http://www.ncbi.nlm.nih.gov/pubmed/26733612", "http://www.ncbi.nlm.nih.gov/pubmed/27565810", "http://www.ncbi.nlm.nih.gov/pubmed/26965285", "http://www.ncbi.nlm.nih.gov/pubmed/27489350", "http://www.ncbi.nlm.nih.gov/pubmed/27048952", "http://www.ncbi.nlm.nih.gov/pubmed/24754926", "http://www.ncbi.nlm.nih.gov/pubmed/27155741", "http://www.ncbi.nlm.nih.gov/pubmed/27012832", "http://www.ncbi.nlm.nih.gov/pubmed/27529512", "http://www.ncbi.nlm.nih.gov/pubmed/26976426" ], "ideal_answer": [ "Pictilisib acts by inhibiting PI3K. It is used for breast cancer treatment." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ], "type": "summary", "id": "5884fed0e56acf5176000011", "snippets": [ { "offsetInBeginSection": 367, "offsetInEndSection": 696, "text": "EXPERIMENTAL DESIGN: Antiestrogen-sensitive and antiestrogen-resistant ER(+) human breast cancer cell lines and mice bearing PIK3CA-mutant xenografts were treated with the antiestrogen fulvestrant, the PI3K inhibitor GDC-0941 (pictilisib; varied doses/schedules that provided similar amounts of drug each week), or combinations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26733612", "endSection": "abstract" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1834, "text": "These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26830312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor-Positive Breast Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26976426", "endSection": "title" }, { "offsetInBeginSection": 201, "offsetInEndSection": 458, "text": "This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26976426", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1100, "text": "In contrast to parental cells, resistant cells were sensitive to growth inhibition and apoptosis induced by the class I PI3K inhibitor, GDC-0941 (pictilisib), which also induced FOXO1 nuclear translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27044711", "endSection": "abstract" }, { "offsetInBeginSection": 57, "offsetInEndSection": 429, "text": "Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearing controls and in addition were increased following dosing with class I PI3K inhibitor pictilisib (GDC-0941).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "The PI3K inhibitor pictilisib plus anastrozole suppresses luminal B breast cancer proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27012832", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 194, "text": "Pictilisib is an oral inhibitor of multiple PI3K isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27155741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27565810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24754926", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25370471", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 563, "text": "PURPOSE: This first-in-human dose-escalation trial evaluated the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I phosphatidylinositol-3-kinases (PI3K).PATIENTS AND METHODS: Sixty patients with solid tumors received pictilisib at 14 dose levels from 15 to 450 mg once-daily, initially on days 1 to 21 every 28 days and later, using continuous dosing for selected dose levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25370471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The PI3K inhibitor pictilisib plus anastrozole suppresses luminal B breast cancer proliferation. \u00a92016 American Association for Cancer Research.Copyright \u00a9 2015.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26830312", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 195, "text": "Pictilisib is an oral inhibitor of multiple PI3K isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27155741", "endSection": "abstract" } ] }, { "body": "What are sirtuins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26463981", "http://www.ncbi.nlm.nih.gov/pubmed/26961318", "http://www.ncbi.nlm.nih.gov/pubmed/26796034" ], "ideal_answer": [ "Seven sirtuins have been identified in humans, and their functions currently surpass their originally identified role as histone deacetylase and chromatin silencers to encompass nutrient sensing and metabolic function. All seven sirtuins require NAD(+) in order to carry out their enzymatic activity, and thus become activated in conditions of nutrient depletion, starvation, and cellular stress." ], "type": "summary", "id": "58e2651c6fddd3e83e000013", "snippets": [ { "offsetInBeginSection": 179, "offsetInEndSection": 577, "text": " seven sirtuins have been identified in humans, and their functions currently surpass their originally identified role as histone deacetylase and chromatin silencers to encompass nutrient sensing and metabolic function. All seven sirtuins require NAD(+) in order to carry out their enzymatic activity, and thus become activated in conditions of nutrient depletion, starvation, and cellular stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Sirtuins are NAD-dependent lysine deacylases that play critical roles in cellular regulation and are implicated in human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26796034", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 160, "text": "Sirtuins are NAD+ -dependent class III histone deacetylases (HDACs) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26961318", "endSection": "abstract" } ] }, { "body": "Which miRNA is targeted by SRY/Sox9?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "http://www.ncbi.nlm.nih.gov/pubmed/23389731", "http://www.ncbi.nlm.nih.gov/pubmed/25580223" ], "ideal_answer": [ "The testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon", "Does the linear Sry transcript function as a ceRNA for miR-138?. Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138. Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1 (HIF-1), and overexpression of SOX4 and HIF-1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. ", ", the sex determining region y ( sry) and the cerebellar degeneration-related protein 1 ( cdr1as) rna transcripts have been described to function as a new class of post-transcriptional regulatory rnas that behave as circular endogenous rna sponges for the micro rnas (mirnas) mir-138 and mir-7 , respectively . ", "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138.", "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively.", "Does the linear Sry transcript function as a ceRNA for miR-138?. Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1 (HIF-1), and overexpression of SOX4 and HIF-1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138. Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. ", "recently, the sex determining region y ( sry) and the cerebellar degeneration-related protein 1 ( cdr1as) rna transcripts have been described to function as a new class of post-transcriptional regulatory rnas that behave as circular endogenous rna sponges for the micro rnas (mirnas) mir-138 and mir-7, respectively.", "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. Metastasis is the major factor affecting patient survival in ovarian cancer. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs.", "Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1\u00ce\u00b1 (HIF-1\u00ce\u00b1), and overexpression of SOX4 and HIF-1\u00ce\u00b1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon.", "Does the linear Sry transcript function as a ceRNA for miR-138? Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively.", "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. Epidermal growth factor receptor acted as the downstream molecule of SOX4 by way of direct transcriptional control, whereas Slug was the downstream molecule of HIF-1\u00ce\u00b1 by way of proteasome-mediated degradation.", "Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), and overexpression of SOX4 and HIF-1\u03b1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. " ], "exact_answer": [ "mir-138" ], "type": "factoid", "id": "58de18e48acda3452900002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Does the linear Sry transcript function as a ceRNA for miR-138?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25580223", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25580223", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 834, "text": " it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25580223", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 742, "text": "Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), and overexpression of SOX4 and HIF-1\u03b1 effectively reversed the miR-138-mediated suppression of cell invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23389731", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1308, "text": "We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23446346", "endSection": "abstract" } ] }, { "body": "Which technique led to the elucidation of the role of HOXD10 in regulating lymphatic endothelial responses to VEGF-C?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27199372" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1415684", "o": "HOXD10" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5032383335380014", "o": "HOXD10" } ], "ideal_answer": [ "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C.", "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C", "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C. " ], "exact_answer": [ "DeepCAGE" ], "concepts": [ "http://www.uniprot.org/uniprot/VEGFC_MOUSE", "http://www.uniprot.org/uniprot/HXD10_SAGLB", "http://www.uniprot.org/uniprot/HXD10_HUMAN", "http://www.uniprot.org/uniprot/HXD10_HETFR", "http://www.uniprot.org/uniprot/HXD10_LAGLA", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004729", "http://www.uniprot.org/uniprot/VEGFC_HUMAN", "http://www.uniprot.org/uniprot/VEGFC_RAT", "http://www.biosemantics.org/jochem#4263666", "http://www.uniprot.org/uniprot/HXD10_CHICK", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042582", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040262", "http://www.uniprot.org/uniprot/HXD10_PANTR", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042442", "http://amigo.geneontology.org/amigo/term/GO:0036328" ], "type": "factoid", "id": "5881f627713cbdfd3d000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27199372", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27199372", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27199372", "endSection": "title" } ] }, { "body": "Is Obeticholic Acid used for treatment of Primary Biliary Cholangitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27406083", "http://www.ncbi.nlm.nih.gov/pubmed/27906472", "http://www.ncbi.nlm.nih.gov/pubmed/27532829", "http://www.ncbi.nlm.nih.gov/pubmed/27621676", "http://www.ncbi.nlm.nih.gov/pubmed/27700211", "http://www.ncbi.nlm.nih.gov/pubmed/27825634", "http://www.ncbi.nlm.nih.gov/pubmed/27468093", "http://www.ncbi.nlm.nih.gov/pubmed/26312413", "http://www.ncbi.nlm.nih.gov/pubmed/27589928" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C2825352", "o": "Obeticholic Acid" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2825352", "o": "http://linkedlifedata.com/resource/umls/label/A17691068" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17691068", "o": "OBETICHOLIC ACID" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0087111", "o": "http://linkedlifedata.com/resource/umls/label/A10762572" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10762572", "o": "Treatment" } ], "ideal_answer": [ "Yes, obeticholic acid is a farnesoid-X receptor agonist that is approved for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0060643", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019468" ], "type": "yesno", "id": "5884722ee56acf5176000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Obeticholic acid in primary biliary cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27825634", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "In a double-blind, randomized, placebo-controlled study including 217 patients with primary biliary cholangitis, the authors show that obeticholic acid (a potent farnesoid X agonist) administered with ursodeoxycholic acid or as monotherapy significantly decreases serum alkaline phosphatase and bilirubin when compared to placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27825634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27406083", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 400, "text": "Obeticholic Acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a second line therapy in PBC and has recently been licenced by the FDA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27589928", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1363, "text": "OCA will be the first stratified therapy introduced in PBC, however confirmatory trial and real life data are needed to confirm that suggestive biochemical improvements are matched by improvement in key clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27589928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621676", "endSection": "title" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1466, "text": "A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621676", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1394, "text": "Although obeticholic acid was approved by the FDA for the treatment of PBC in May 2016, this development occurred after the symposium presentation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27700211", "endSection": "abstract" }, { "offsetInBeginSection": 2330, "offsetInEndSection": 2511, "text": "While several agents are being studied in combination with UDCA, monotherapy with the novel agent obeticholic acid, a farnesoid X receptor agonist, has also shown promising results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27700211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 452, "text": "Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27406083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Obeticholic acid for the treatment of primary biliary cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27468093", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906472", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27532829", "endSection": "title" }, { "offsetInBeginSection": 513, "offsetInEndSection": 654, "text": "This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27406083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Obeticholic acid for the treatment of primary biliary cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27468093", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Long-term Clinical Impact and Cost-Effectiveness of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906472", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Obeticholic acid in primary biliary cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27825634", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27532829", "endSection": "title" }, { "offsetInBeginSection": 515, "offsetInEndSection": 656, "text": "This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27406083", "endSection": "abstract" } ] }, { "body": "What alternate indication has Vanoxerine been repositioned for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21615815", "http://www.ncbi.nlm.nih.gov/pubmed/27108936", "http://www.ncbi.nlm.nih.gov/pubmed/19817928", "http://www.ncbi.nlm.nih.gov/pubmed/19817929", "http://www.ncbi.nlm.nih.gov/pubmed/25684233", "http://www.ncbi.nlm.nih.gov/pubmed/26616666" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0164200", "o": "vanoxerine" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0164200", "o": "http://linkedlifedata.com/resource/umls/label/A17685361" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17685361", "o": "VANOXERINE" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0164200", "o": "http://linkedlifedata.com/resource/umls/label/A0294723" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0294723", "o": "vanoxerine" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0556030", "o": "repositioning" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0556030", "o": "http://linkedlifedata.com/resource/umls/label/A15558315" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15558315", "o": "Repositioned" } ], "ideal_answer": [ "Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter. Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy.", "Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy. Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter. ", "Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction and can potential treat atrial fibrillation", "Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy. Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter.", "vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter.", "Vanoxerine 's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter.", "vanoxerine's were strongly frequency-dependent and repositioned it for treatment of atrial fibrillation and flutter. . has been in clinical trials for parkinsonism , depression and cocaine addiction but lacked efficacy. . " ], "exact_answer": [ "atrial fibrillation and flutter" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056687", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4001200", "http://www.biosemantics.org/jochem#4001200", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4258722", "http://www.biosemantics.org/jochem#4151584", "http://www.biosemantics.org/jochem#4258722", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4151584", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001145" ], "type": "factoid", "id": "58c9a8fe02b8c6095300002a", "snippets": [ { "offsetInBeginSection": 272, "offsetInEndSection": 399, "text": "Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Vanoxerine: cellular mechanism of a new antiarrhythmic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19817928", "endSection": "title" }, { "offsetInBeginSection": 231, "offsetInEndSection": 294, "text": "Therefore, we proposed that vanoxerine might be antiarrhythmic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19817929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Vanoxerine is a promising, new, investigational antiarrhythmic drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615815", "endSection": "title" }, { "offsetInBeginSection": 269, "offsetInEndSection": 396, "text": "Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616666", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 308, "text": "Therefore, we proposed that vanoxerine might be antiarrhythmic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19817929", "endSection": "abstract" }, { "offsetInBeginSection": 1592, "offsetInEndSection": 1674, "text": "Vanoxerine has characteristics of a potentially effective and safe antiarrhythmic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19817928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "BACKGROUND: Vanoxerine is a promising, new, investigational antiarrhythmic drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615815", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Vanoxerine, a new drug for terminating atrial fibrillation and flutter.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19817929", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 164, "text": "Vanoxerine is an oral, 1,4-dialkylpiperazine derivative antiarrhythmic drug being evaluated for pharmacological cardioversion of atrial fibrillation (AF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27108936", "endSection": "abstract" }, { "offsetInBeginSection": 1420, "offsetInEndSection": 1535, "text": "Oral vanoxerine converted AF/AFL to SR at a high rate, was well tolerated, and caused no ventricular proarrhythmia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25684233", "endSection": "abstract" } ] }, { "body": "What is the applicability of the No Promoter Left Behind method?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26530723" ], "ideal_answer": [ "No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing promoter architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements.", "Promoters have diverse regulatory architectures and thus activate genes differently. No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing such diverse architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements." ], "exact_answer": [ "Learning de novo promoter architectures from genome-wide transcription start sites." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018507", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005786", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011401" ], "type": "factoid", "id": "588f341594c1512c50000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "No Promoter Left Behind (NPLB): learn de novo promoter architectures from genome-wide transcription start sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530723", "endSection": "title" }, { "offsetInBeginSection": 249, "offsetInEndSection": 472, "text": "No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing such diverse architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530723", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 457, "text": "No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing such diverse architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530723", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 459, "text": "No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing such diverse architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "No Promoter Left Behind (NPLB): learn de novo promoter architectures from genome-wide transcription start sites", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530723", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "No Promoter Left Behind (NPLB): learn de novo promoter architectures from genome-wide transcription start sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530723", "endSection": "title" }, { "offsetInBeginSection": 237, "offsetInEndSection": 460, "text": "No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing such diverse architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530723", "endSection": "abstract" } ] }, { "body": "Which mutated genes are associated with isolated ectopia lentis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20702823", "http://www.ncbi.nlm.nih.gov/pubmed/20082464", "http://www.ncbi.nlm.nih.gov/pubmed/24406422", "http://www.ncbi.nlm.nih.gov/pubmed/21051722", "http://www.ncbi.nlm.nih.gov/pubmed/22871183", "http://www.ncbi.nlm.nih.gov/pubmed/18079676", "http://www.ncbi.nlm.nih.gov/pubmed/22539873", "http://www.ncbi.nlm.nih.gov/pubmed/19390640", "http://www.ncbi.nlm.nih.gov/pubmed/26653794", "http://www.ncbi.nlm.nih.gov/pubmed/21989719", "http://www.ncbi.nlm.nih.gov/pubmed/25654236", "http://www.ncbi.nlm.nih.gov/pubmed/25900864", "http://www.ncbi.nlm.nih.gov/pubmed/22950452", "http://www.ncbi.nlm.nih.gov/pubmed/25975359", "http://www.ncbi.nlm.nih.gov/pubmed/23426735", "http://www.ncbi.nlm.nih.gov/pubmed/17679947", "http://www.ncbi.nlm.nih.gov/pubmed/16765689", "http://www.ncbi.nlm.nih.gov/pubmed/22219643", "http://www.ncbi.nlm.nih.gov/pubmed/22736615", "http://www.ncbi.nlm.nih.gov/pubmed/20141359", "http://www.ncbi.nlm.nih.gov/pubmed/19200529" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1705285", "o": "http://linkedlifedata.com/resource/umls/label/A19043125" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A19043125", "o": "Mutated" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1851286", "o": "Ectopia lentis isolated" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1851286", "o": "http://linkedlifedata.com/resource/umls/label/A18467573" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1705285", "o": "mutation" } ], "ideal_answer": [ "Isolated ectopia lentis (EL) is caused by mutation in genes:\n1) ADAMTSL4 and \n2) Fibrillin-1 (FBN1)." ], "exact_answer": [ [ "ADAMTSL4" ], [ "Fibrillin-1", "FBN1" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004479" ], "type": "list", "id": "58d8d8108acda34529000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A founder mutation in ADAMTSL4 causes early-onset bilateral ectopia lentis among Jews of Bukharian origin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653794", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "The term isolated ectopia lentis (EL; subluxation or dislocation of the human crystalline lens) is applied to patients with EL, without skeletal features and in the absence of aortic root dilatation. To date, the only gene shown to cause autosomal-recessive isolated EL is ADAMTSL4. Here we report a novel founder mutation in ADAMTSL4 gene in children of Bukharian Jewish origin presenting with early-onset bilateral EL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Early onset ectopia lentis due to a FBN1 mutation with non-penetrance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25900864", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Isolated ectopia lentis is usually autosomal dominant and commonly due to the mutations of FBN1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25900864", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 810, "text": "In conclusion, we report on a case of early-onset autosomal dominant isolated ectopia lentis caused by FBN1 mutation that has previously been reported only in Marfan syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25900864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "ADAMTSL4-associated isolated ectopia lentis: Further patients, novel mutations and a detailed phenotype description.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25975359", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "ADAMTSL4 mutations seem to be the most common cause of isolated ectoplia lentis (EL) and thus are important concerning the differential diagnosis of connective tissue syndromes with EL as main feature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25975359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "A genotype-phenotype comparison of ADAMTSL4 and FBN1 in isolated ectopia lentis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22736615", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 168, "text": "To describe the genotype-phenotype relationship of a cohort of consecutive patients with isolated ectopia lentis (EL) secondary to ADAMTSL4 and FBN1 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22736615", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1769, "text": "ADAMTSL4 is the most important known causative gene in isolated EL. Mutations in ADAMTSL4 appear to cause earlier manifestation of EL and are associated with increased axial length as compared to FBN1. We suggest that ADAMTSL4 be screened in all patients with isolated EL and that physicians be vigilant for the more severe ocular phenotype associated with mutations in this gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22736615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "A novel FBN1 mutation in a Chinese family with isolated ectopia lentis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22539873", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 101, "text": "To identify the genetic defect in an autosomal dominant isolated ectopia lentis (EL) family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22539873", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1144, "text": "A novel mutation of FBN1 results in an arginine to cysteine residue (p.R974C) substitution, which is responsible for the patients with isolated EL in this Chinese family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22539873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19200529", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Isolated ectopia lentis is usually autosomal dominant and commonly due to the mutations of FBN1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25900864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "To examine the fibrillin-1 (FBN1) gene for mutations in members of a Chinese family with isolated ectopia lentis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16765689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Ophthalmic findings in a family with early-onset isolated ectopia lentis and the p.Arg62Cys mutation of the fibrillin-1 gene (FBN1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22950452", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Craniosynostosis with ectopia lentis and a homozygous 20-base deletion in ADAMTSL4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22871183", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "ADAMTSL4-associated isolated ectopia lentis: Further patients, novel mutations and a detailed phenotype description", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25975359", "endSection": "title" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1509, "text": "Our study presented detailed clinical manifestations, including some novel ophthalmic findings, such as pupillary abnormality, different types of glaucoma, and progressive hyperopia.Ophthalmic findings and the p.Arg62Cys mutation of FBN1 gene were reported in a family with early-onset isolated ectopia lentis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22950452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "To examine the fibrillin-1 (FBN1) gene for mutations in members of a Chinese family with isolated ectopia lentis.Clinically relevant laboratory investigation.Family members underwent clinical examinations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16765689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Ophthalmic findings in a family with early-onset isolated ectopia lentis and the p.Arg62Cys mutation of the fibrillin-1 gene (FBN1)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22950452", "endSection": "title" }, { "offsetInBeginSection": 335, "offsetInEndSection": 920, "text": "The 65 exons of FBN1 were amplified by polymerase chain reaction and screened for mutations by a combination of denaturing high-performance liquid chromatography analysis and direct DNA sequencing.A mutation, c.184C-->T in exon 2 of FBN1, which results in substitution of arginine by cysteine at position 62 of the fibrillin-1 protein (p.R62C) in all affected family members but in none of the unaffected individuals.A recurrent mutation of FBN1 gene resulted in an arginine-to-cysteine residue (p.R62C), is responsible for the patients with isolated ectopia lentis in a Chinese family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16765689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Isolated ectopia lentis is usually autosomal dominant and commonly due to the mutations of FBN1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25900864", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 846, "text": "CONCLUSIONS: The results emphasize the association of ADAMTSL4 null mutations with isolated ectopia lentis and the presence of a founder mutation in the European population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21051722", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 1052, "text": "Herein we show a consanguineous family that carries a novel homozygous splice mutation IVS4-1G>A/IVS4-1G>A in ADAMTSL4 responsible for isolated autosomal recessive EL, thus confirming the involvement of this gene in this condition and underlining the major role of ADAMTS proteases in zonular fibers homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20141359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Two novel FBN1 mutations associated with ectopia lentis and marfanoid habitus in two Chinese families.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19390640", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Novel FBN1 mutations associated with predominant ectopia lentis and marfanoid habitus in Chinese patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17679947", "endSection": "title" }, { "offsetInBeginSection": 203, "offsetInEndSection": 402, "text": "FBN1 mutations are associated with multiple clinical phenotypes, including Marfan syndrome (MFS), MASS phenotype, and familial ectopia lentis, but rarely with isolated aortic aneurysm and dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20082464", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 387, "text": "This was correlated with Sanger sequencing of ADAMTSL4 and FBN1 genes.Seventeen patients were examined, including one with ectopia lentis et pupillae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22736615", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 739, "text": "Recently, ADAMTSL4 has been shown to be responsible for isolated autosomal recessive ectopia lentis in an inbred family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20141359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Confirmation of ADAMTSL4 mutations for autosomal recessive isolated bilateral ectopia lentis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20141359", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "A recurrent FBN1 mutation in an autosomal dominant ectopia lentis family of Indian origin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18079676", "endSection": "title" }, { "offsetInBeginSection": 1558, "offsetInEndSection": 1737, "text": "We suggest that ADAMTSL4 be screened in all patients with isolated EL and that physicians be vigilant for the more severe ocular phenotype associated with mutations in this gene..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22736615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19200529", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Recurrent FBN1 mutation (R62C) in a Chinese family with isolated ectopia lentis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16765689", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "A genotype-phenotype comparison of ADAMTSL4 and FBN1 in isolated ectopia lentis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22736615", "endSection": "title" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1514, "text": "Ophthalmic findings and the p.Arg62Cys mutation of FBN1 gene were reported in a family with early-onset isolated ectopia lentis..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22950452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Ophthalmic findings in a family with early-onset isolated ectopia lentis and the p.Arg62Cys mutation of the fibrillin-1 gene (FBN1).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22950452", "endSection": "title" }, { "offsetInBeginSection": 756, "offsetInEndSection": 926, "text": "A recurrent mutation of FBN1 gene resulted in an arginine-to-cysteine residue (p.R62C), is responsible for the patients with isolated ectopia lentis in a Chinese family..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16765689", "endSection": "abstract" } ] }, { "body": "Does the word ovine refers to goats?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23903827", "http://www.ncbi.nlm.nih.gov/pubmed/25755186", "http://www.ncbi.nlm.nih.gov/pubmed/11578130" ], "ideal_answer": [ "Ovine refers to sheep." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012756", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034561" ], "type": "yesno", "id": "58e186fd6fddd3e83e00000f", "snippets": [ { "offsetInBeginSection": 147, "offsetInEndSection": 320, "text": "Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23903827", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 304, "text": "In sheep, a bronchiolo-alveolar carcinoma, known as ovine pulmonary carcinoma (OPC), is caused by jaagsiekte sheep retrovirus (JSRV), an exogenous type D retrovirus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11578130", "endSection": "abstract" } ] }, { "body": "Does GATA-1 regulate ribosomal protein genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19587786", "http://www.ncbi.nlm.nih.gov/pubmed/10224082", "http://www.ncbi.nlm.nih.gov/pubmed/24453067" ], "ideal_answer": [ "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). ", "in exon 2 interfere with the synthesis of the full-length isoform of gata-1 and lead to the production of a shortened isoform , gata-1s these mutations have been found in patients with diamond-blackfan anemia (dba) , a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. . of the corresponding transcription factors are of particular interest , as they are housekeeping genes or show a direct link to hematopoiesis , tumorigenesis or leukemia (e.g gata-1/2 , pu.1 , mzf-1). . ", "These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). ", "These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g.", "These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. The Ribosomal protein S19 gene locus (RPS19) has been linked to two kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA) and Transient Erythroblastopenia in Childhood (TEC).", "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins.", "mutations in exon 2 interfere with the synthesis of the full-length isoform of gata-1 and lead to the production of a shortened isoform, gata-1s.", "yes", "Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins." ], "exact_answer": "yes", "type": "yesno", "id": "58e782fd3e8b6dc87c000006", "snippets": [ { "offsetInBeginSection": 127, "offsetInEndSection": 451, "text": "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24453067", "endSection": "abstract" }, { "offsetInBeginSection": 1248, "offsetInEndSection": 1453, "text": "Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19587786", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1028, "text": "Deletion of PKC1 relieves the repression of both ribosomal protein and rRNA genes that occurs in response to a defect in the secretory pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10224082", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1360, "text": "This stress is monitored by Pkc1p, which initiates a signal transduction pathway that leads to repression of transcription of the rRNA and ribosomal protein genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10224082", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1578, "text": "The importance of the transcription of the 137 ribosomal protein genes to the economy of the cell is apparent from the existence of at least three distinct pathways that can effect the repression of this set of genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10224082", "endSection": "abstract" } ] }, { "body": "Which gene mutations cause the Marfan syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3354620", "http://www.ncbi.nlm.nih.gov/pubmed/8841521", "http://www.ncbi.nlm.nih.gov/pubmed/7611299", "http://www.ncbi.nlm.nih.gov/pubmed/22221020", "http://www.ncbi.nlm.nih.gov/pubmed/9649943", "http://www.ncbi.nlm.nih.gov/pubmed/1569206", "http://www.ncbi.nlm.nih.gov/pubmed/12511552", "http://www.ncbi.nlm.nih.gov/pubmed/20538085", "http://www.ncbi.nlm.nih.gov/pubmed/19161152", "http://www.ncbi.nlm.nih.gov/pubmed/19839986", "http://www.ncbi.nlm.nih.gov/pubmed/19328768", "http://www.ncbi.nlm.nih.gov/pubmed/8008028", "http://www.ncbi.nlm.nih.gov/pubmed/24668922", "http://www.ncbi.nlm.nih.gov/pubmed/23684891", "http://www.ncbi.nlm.nih.gov/pubmed/21883168", "http://www.ncbi.nlm.nih.gov/pubmed/19159394", "http://www.ncbi.nlm.nih.gov/pubmed/15287423", "http://www.ncbi.nlm.nih.gov/pubmed/23552953", "http://www.ncbi.nlm.nih.gov/pubmed/18388785", "http://www.ncbi.nlm.nih.gov/pubmed/21909107", "http://www.ncbi.nlm.nih.gov/pubmed/9401003", "http://www.ncbi.nlm.nih.gov/pubmed/23653584", "http://www.ncbi.nlm.nih.gov/pubmed/7870075", "http://www.ncbi.nlm.nih.gov/pubmed/17701892", "http://www.ncbi.nlm.nih.gov/pubmed/27906200", "http://www.ncbi.nlm.nih.gov/pubmed/11251996", "http://www.ncbi.nlm.nih.gov/pubmed/18377530", "http://www.ncbi.nlm.nih.gov/pubmed/12413333", "http://www.ncbi.nlm.nih.gov/pubmed/25812041", "http://www.ncbi.nlm.nih.gov/pubmed/8941093", "http://www.ncbi.nlm.nih.gov/pubmed/18435798", "http://www.ncbi.nlm.nih.gov/pubmed/11826022", "http://www.ncbi.nlm.nih.gov/pubmed/10633129", "http://www.ncbi.nlm.nih.gov/pubmed/8180508", "http://www.ncbi.nlm.nih.gov/pubmed/1406753", "http://www.ncbi.nlm.nih.gov/pubmed/10721679", "http://www.ncbi.nlm.nih.gov/pubmed/18412115", "http://www.ncbi.nlm.nih.gov/pubmed/12402346", "http://www.ncbi.nlm.nih.gov/pubmed/21034599", "http://www.ncbi.nlm.nih.gov/pubmed/10441700", "http://www.ncbi.nlm.nih.gov/pubmed/19353630", "http://www.ncbi.nlm.nih.gov/pubmed/8882780", "http://www.ncbi.nlm.nih.gov/pubmed/24078565", "http://www.ncbi.nlm.nih.gov/pubmed/21211293", "http://www.ncbi.nlm.nih.gov/pubmed/12651868", "http://www.ncbi.nlm.nih.gov/pubmed/10189088", "http://www.ncbi.nlm.nih.gov/pubmed/16799921", "http://www.ncbi.nlm.nih.gov/pubmed/11175294", "http://www.ncbi.nlm.nih.gov/pubmed/10694921", "http://www.ncbi.nlm.nih.gov/pubmed/26503076", "http://www.ncbi.nlm.nih.gov/pubmed/23121584", "http://www.ncbi.nlm.nih.gov/pubmed/10756346", "http://www.ncbi.nlm.nih.gov/pubmed/10766875", "http://www.ncbi.nlm.nih.gov/pubmed/15861007", "http://www.ncbi.nlm.nih.gov/pubmed/8405806" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0596611", "o": "Gene Mutation" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0596611", "o": "http://linkedlifedata.com/resource/umls/label/A7647895" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7647895", "o": "Gene Mutation" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0596611", "o": "http://linkedlifedata.com/resource/umls/label/A7850263" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7850263", "o": "Gene Mutation" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0024796", "o": "Marfan Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0024796", "o": "http://linkedlifedata.com/resource/umls/label/A0431931" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0596611", "o": "http://linkedlifedata.com/resource/umls/label/A18566680" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18566680", "o": "gene mutations" } ], "ideal_answer": [ "Marfan syndrome (MFS) is an autosomal dominant disorder caused by mutations in the fibrillin 1 gene (FBN1)." ], "exact_answer": [ "fibrillin 1 gene", "FBN1" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382", "http://www.disease-ontology.org/api/metadata/DOID:14323" ], "type": "factoid", "id": "58d8e6818acda3452900000a", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 126, "text": "The diagnostic criteria of Marfan syndrome (MFS) highlight the importance of a FBN1 mutation test in diagnosing MFS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25812041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A marked decrease in heart rate variability in Marfan syndrome patients with confirmed FBN1 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503076", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 199, "text": "The studies on heart rate variability (HRV), a key predictor of all-cause mortality, in Marfan syndrome (MS), up to now have not been reported, especially in patients with FBN1 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503076", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 315, "text": "Among 18 MS patients with the phenotype of MS meeting inclusion criteria 15 have had a FBN1 gene mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503076", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 637, "text": "Heart rates in MS patients with the FBN1 mutation were increased in both the supine position and orthostatic test (p<0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503076", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 985, "text": "A marked decrease in HRV, documented in the study, may be an important clinical feature in MS patients with confirmed FBN1 gene mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Evaluating the quality of Marfan genotype-phenotype correlations in existing FBN1 databases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906200", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 102, "text": "Genetic FBN1 testing is pivotal for confirming the clinical diagnosis of Marfan syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Novel FBN1 gene mutation and maternal germinal mosaicism as the cause of neonatal form of Marfan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24668922", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Marfan syndrome (MFS) is an autosomal dominant disorder caused by mutations in the fibrillin 1 gene (FBN1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24668922", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 491, "text": "While mutations causing classic manifestations of Marfan syndrome have been identified throughout the FBN1 gene, the six previously characterized mutations resulting in the severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of the gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8882780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "[Screening of FBN1 gene mutations in a family with Marfan syndrome].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211293", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "To identify FBN1 gene mutations in a Chinese family with Marfan syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21211293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Identification of fibrillin-1 gene mutations in Marfan syndrome by high-resolution melting analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19328768", "endSection": "title" }, { "offsetInBeginSection": 51, "offsetInEndSection": 458, "text": "Three diagnostic classifications comprising first, Marfan genotype with a causative FBN1 gene mutation; second, Marfan phenotype with clinical criteria of the original Ghent nosology (Ghent-1); and third, phenotype with clinical criteria of its current revision (Ghent-2) in 300 consecutive persons referred for confirmation or exclusion of Marfan syndrome (150 men, 150 women aged 35 \u00b1 13 years) were used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21883168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Prevalence of dural ectasia in 63 gene-mutation-positive patients with features of Marfan syndrome type 1 and Loeys-Dietz syndrome and report of 22 novel FBN1 mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19159394", "endSection": "title" }, { "offsetInBeginSection": 85, "offsetInEndSection": 155, "text": "Marfan syndrome type 1 (MFS1) is caused by mutations in the FBN1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19159394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721679", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 222, "text": "Mutations in FBN1, TGFBR1, TGFBR2 are known to cause Marfan syndrome (MIM 154700), a pleiotropic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11175294", "endSection": "title" }, { "offsetInBeginSection": 1088, "offsetInEndSection": 1345, "text": "We conclude that fibrillin gene defects cause familial Marfan syndrome, that mutations in the EGF-like motif of the fibrillin gene are not uniformly associated with severe disease, and that fibrillin genotype is not the sole determinant of Marfan phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1569206", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Mutations of the fibrillin gene (FBN1) are known to cause classical Marfan's syndrome, ectopia lentis and neonatal Marfan's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7870075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Severe Marfan syndrome due to FBN1 exon deletions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18412115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "BACKGROUND: Mutations in the FBN1 gene are the cause of the Marfan syndrome, an autosomal dominant disorder with skeletal, ocular, and cardiovascular complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8941093", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 696, "text": "It is still difficult to use modern genetic testing for diagnosis because Marfan syndrome can be caused by many different mutations in FBN1, a large gene with 65 coding segments, while mutations in other genes can cause overlapping phenotypes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23121584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "The studies on heart rate variability (HRV), a key predictor of all-cause mortality, in Marfan syndrome (MS), up to now have not been reported, especially in patients with FBN1 mutations.Among 18 MS patients with the phenotype of MS meeting inclusion criteria 15 have had a FBN1 gene mutation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause Marfan syndrome (MFS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22221020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17701892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Mutations in the gene encoding fibrillin-1 (FBN1) cause Marfan syndrome (MFS) and other related connective tissue disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12402346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19353630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The aim of this study was to establish a national database of mutations in the fibrillin-1 (FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19839986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18435798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Mutations in the gene encoding fibrillin 1 (FBN1) cause Marfan syndrome (MFS), and related connective tissue disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19161152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Acute mitral regurgitation due to chordal rupture in a patient with neonatal Marfan syndrome caused by a deletion in exon 29 of the FBN1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10441700", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Neonatal Marfan syndrome caused by an exon 25 mutation of the fibrillin-1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15287423", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Functional pulmonary atresia in a patient with neonatal Marfan syndrome caused by a c.3602G>A mutation in exon 29 of the FBN1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18388785", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11175294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "It has been firmly established that mutations in the gene for fibrillin 1, FBN1, cause Marfan syndrome (MFS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11826022", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 282, "text": "Mutations in the fibrillin-1 gene (FBN1) cause Marfan syndrome and related connective tissue disorders (fibrillinopathies) that show autosomal dominant inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12651868", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 623, "text": "It is known that mutations in the fibrillin gene cause a heterogenous connective tissue disease called Marfan syndrome [2], so information on mechanical properties of microfibrils or their role in tissue function would be useful.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8841521", "endSection": "abstract" }, { "offsetInBeginSection": 1727, "offsetInEndSection": 1856, "text": "Mutations in the fibrillin gene located on human chromosome 15 have been strongly implicated as the cause of the Marfan syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19353630", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 261, "text": "Mutations within the fibrillin-1 gene cause Marfan syndrome (MFS), a heritable disease of connective tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12511552", "endSection": "abstract" }, { "offsetInBeginSection": 878, "offsetInEndSection": 1013, "text": "These data speak against the hypothesis that mutations in one or more of these 3 fibrillar collagens cause the classic Marfan syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3354620", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 1074, "text": "By WES and filtering with a mining tool, a novel FBN1 missense variant was found in patient 1 and his mother, who both showed clinical features of Marfan syndrome by thorough anthropometric assessment, and a novel EYA1 missense variant as a probable cause of the renal malformation in the patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23552953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17701892", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 781, "text": "FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21909107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Marfan syndrome is a multisystem disorder of connective tissue that is inherited in an autosomal dominant fashion, and results from mutation of the FBN1 gene on human chromosome 15.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23121584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11175294", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 661, "text": "We here report 22 novel and 9 recurrent mutations in the FBN1 gene in 36 patients with clinical features of Marfan syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19159394", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 195, "text": "The fibrillin gene is the site of mutations causing Marfan's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8008028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18435798", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 344, "text": "FBN1 at 15q21.1 was found to cause Marfan syndrome in 1991, and in 2004 TGFBR2 at 3p24.1 was newly identified as the Marfan syndrome type II gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15861007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7611299", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Mutations in the gene encoding fibrillin-1 (FBN1) cause Marfan syndrome (MFS) and other related connective tissue disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12402346", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 540, "text": "Mutations in the gene coding for fibrillin-1, FBN1, are known to cause Marfan syndrome, and have been identified in almost all exons of FBN1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10189088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause the Marfan syndrome (MFS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7611299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The aim of this study was to establish a national database of mutations in the fibrillin-1 (FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19839986", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 493, "text": "While mutations causing classic manifestations of Marfan syndrome have been identified throughout the FBN1 gene, the six previously characterized mutations resulting in the severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of the gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8882780", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 358, "text": "Mutations in the fibrillin-1 (FBN1) gene, on chromosome 15q21.1, have been found to cause Marfan syndrome, a dominantly inherited disorder characterised by clinically variable skeletal, ocular, and cardiovascular abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9401003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Mutations in the gene for fibrillin-1 (FBN1) have been shown to cause Marfan syndrome, an autosomal dominant disorder of connective tissue characterised by pleiotropic manifestations involving primarily the ocular, skeletal, and cardiovascular systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10633129", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 332, "text": "Through a number of investigational approaches, the gene encoding for fibrillin, the FBN1 gene on chromosome 15, has been identified as the defective gene causing the Marfan syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8180508", "endSection": "abstract" } ] }, { "body": "What is the indication of ARCALYST?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22096352", "http://www.ncbi.nlm.nih.gov/pubmed/19707454", "http://www.ncbi.nlm.nih.gov/pubmed/19649332" ], "ideal_answer": [ "In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for rilonacept in the treatment of two cryopyrin-associated periodic syndromes (CAPS) disorders, namely, familial cold-induced autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), for children and adults 12 years and older." ], "exact_answer": [ "cryopyrin-associated periodic syndromes (CAPS) disorders" ], "type": "factoid", "id": "58df47f08acda3452900002f", "snippets": [ { "offsetInBeginSection": 526, "offsetInEndSection": 775, "text": "Rilonacept (Arcalyst(TM); Regeneron) is the first us Food and Drug Administration-approved treatment for familial cold autoinflammatory syndrome and Muckle-Wells syndrome and the first in a new line of drugs designed for longer-acting IL-1 blockade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22096352", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 735, "text": " In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for rilonacept in the treatment of two cryopyrin-associated periodic syndromes (CAPS) disorders, namely, familial cold-induced autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), for children and adults 12 years and older. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19649332", "endSection": "abstract" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1605, "text": "In February, 2008, 'Orphan Drug' approval from the Food and Drug Administration (FDA) for rilonacept (IL-1 Trap/Arcalyst(), Regeneron Pharmaceuticals, Inc) was given for the treatment of two CAPS disorders, FCAS and MWS in adults and children 12 years and older, making rilonacept the first therapy approved for the treatment of CAPS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707454", "endSection": "abstract" } ] }, { "body": "What is ChIPpeakAnno?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20459804" ], "ideal_answer": [ "ChIPpeakAnno is a Bioconductor package within the statistical programming environment R that facilitates batch annotation of enriched peaks identified from ChIP-seq, ChIP-chip, cap analysis of gene expression (CAGE) or any experiments resulting in a large number of enriched genomic regions." ], "type": "summary", "id": "587d13c0d673c3eb14000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459804", "endSection": "title" }, { "offsetInBeginSection": 706, "offsetInEndSection": 1011, "text": "We have developed ChIPpeakAnno as a Bioconductor package within the statistical programming environment R to facilitate batch annotation of enriched peaks identified from ChIP-seq, ChIP-chip, cap analysis of gene expression (CAGE) or any experiments resulting in a large number of enriched genomic regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459804", "endSection": "abstract" }, { "offsetInBeginSection": 1719, "offsetInEndSection": 2187, "text": "ChIPpeakAnno enables batch annotation of the binding sites identified from ChIP-seq, ChIP-chip, CAGE or any technology that results in a large number of enriched genomic regions within the statistical programming environment R. Allowing users to pass their own annotation data such as a different Chromatin immunoprecipitation (ChIP) preparation and a dataset from literature, or existing annotation packages, such as GenomicFeatures and BSgenome, provides flexibility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459804", "endSection": "abstract" } ] }, { "body": "Signaling of which pathways is inhibited by Dupilumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27130691", "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "http://www.ncbi.nlm.nih.gov/pubmed/26454361", "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "http://www.ncbi.nlm.nih.gov/pubmed/27334730", "http://www.ncbi.nlm.nih.gov/pubmed/26440137", "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "http://www.ncbi.nlm.nih.gov/pubmed/25645542", "http://www.ncbi.nlm.nih.gov/pubmed/26308331", "http://www.ncbi.nlm.nih.gov/pubmed/27525671", "http://www.ncbi.nlm.nih.gov/pubmed/27637004", "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "http://www.ncbi.nlm.nih.gov/pubmed/27497276", "http://www.ncbi.nlm.nih.gov/pubmed/26967382", "http://www.ncbi.nlm.nih.gov/pubmed/27223113", "http://www.ncbi.nlm.nih.gov/pubmed/26457448", "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "http://www.ncbi.nlm.nih.gov/pubmed/26836729", "http://www.ncbi.nlm.nih.gov/pubmed/25542094", "http://www.ncbi.nlm.nih.gov/pubmed/24275927" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0037083", "o": "http://linkedlifedata.com/resource/umls/label/A7662356" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7662356", "o": "Signaling" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1710082", "o": "http://linkedlifedata.com/resource/umls/label/A17472893" } ], "ideal_answer": [ "Dupilumab, a fully human anti-interleukin-4 receptor \u03b1 monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling. It is used for treatment of atopic or allergic diseases." ], "exact_answer": [ [ "interleukin-4" ], [ "interleukin-13" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0023052", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015398" ], "type": "list", "id": "5880b2a6c872c95565000004", "snippets": [ { "offsetInBeginSection": 724, "offsetInEndSection": 1170, "text": "This study reviewed all studies about any roles of IL-4 that can directly and indirectly be played in the development of pemphigus and IL-4 inhibition with interferons and dupilumab therapy were introduced as a novel pemphigus treatment for patients who are in relapse phase of the disease. Dupilumab was also introduced as a possible treatment for patients with severe pemphigus. It can directly inhibit IL-4 by targeting IL-4 \u03b1-chain receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26440137", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 276, "text": "OBJECTIVE: To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26836729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND: Dupilumab, a fully human anti-interleukin-4 receptor \u03b1 monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27130691", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1158, "text": "Anti-IL-4 and IL-13 agents (dupilumab, lebrikizumab, and tralokinumab) which block different Th-2 inflammatory pathways and agents targeting the Th-17 inflammatory pathway in severe refractory asthma are under development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27334730", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1337, "text": "Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor \u03b1-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27497276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 614, "text": "The world's first prospective controlled studies with the biologic human anti-IL4R antibody dupilumab for the indication \"atopic dermatitis\" were published in 2014.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25645542", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 803, "text": "An IL-4R antagonist, dupilumab, is the first drug that shows great promise in phase II trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25542094", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 818, "text": "Dupilumab, a humanized monoclonal antibody to the interteukin-4R is the first antibody (i.e. 'biological') with published efficacy shown in controlled prospective studies in atopic dermatitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26308331", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 271, "text": "Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor \u03b1 subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 368, "text": "Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26454361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 974, "text": "The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Dupilumab, a fully human anti-interleukin-4 receptor \u03b1 monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27130691", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 271, "text": "Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor \u03b1 subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 684, "text": "In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor \ufffd, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized.OBJECTIVES: We sought to evaluate dupilumab modulation of the AD molecular signature.METHODS: We performed transcriptomic analyses of pretreatment and posttreatment skin biopsy specimens from patients with moderate-to-severe AD treated weekly with 150 or 300 mg of dupilumab or placebo.RESULTS: Exacerbation of the AD transcriptome was observed in placebo-treated patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 272, "text": "Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor \u03b1 subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 370, "text": "Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 978, "text": "The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 683, "text": "In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor \u00e1, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized.OBJECTIVES: We sought to evaluate dupilumab modulation of the AD molecular signature.METHODS: We performed transcriptomic analyses of pretreatment and posttreatment skin biopsy specimens from patients with moderate-to-severe AD treated weekly with 150 or 300 mg of dupilumab or placebo.RESULTS: Exacerbation of the AD transcriptome was observed in placebo-treated patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "endSection": "abstract" } ] }, { "body": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22627319" ], "ideal_answer": [ "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.", "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia. Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005). ", "Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005). Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.", "among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the top2b/top2a ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (hr, 0.24; p=0.002) and overall survival (hr, 0.29; p=0.005).", "yes", "Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.", "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia" ], "exact_answer": "yes", "type": "yesno", "id": "58b67fae22d3005309000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "title" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1496, "text": "Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 964, "text": "Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1279, "text": "Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "title" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1453, "text": "Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005).Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1499, "text": "CONCLUSION: Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1458, "text": "Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "title" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1252, "text": "Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 936, "text": "Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22627319", "endSection": "abstract" } ] }, { "body": "List the three main structures of the cytoskeleton.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26498781" ], "ideal_answer": [ "Fibrillar polymers-actin filaments, microtubules, and intermediate filaments-are major constituents of the cytoskeleton." ], "exact_answer": [ [ "actin filaments" ], [ "microtubules" ], [ "intermediate filaments" ] ], "type": "list", "id": "58e0035f6fddd3e83e000009", "snippets": [ { "offsetInBeginSection": 177, "offsetInEndSection": 297, "text": "Fibrillar polymers-actin filaments, microtubules, and intermediate filaments-are major constituents of the cytoskeleton,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26498781", "endSection": "abstract" } ] }, { "body": "What is the genus for the common European honey bee?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18941909", "http://www.ncbi.nlm.nih.gov/pubmed/26990560", "http://www.ncbi.nlm.nih.gov/pubmed/27518068", "http://www.ncbi.nlm.nih.gov/pubmed/27447542", "http://www.ncbi.nlm.nih.gov/pubmed/27705831", "http://www.ncbi.nlm.nih.gov/pubmed/19909977", "http://www.ncbi.nlm.nih.gov/pubmed/21960435", "http://www.ncbi.nlm.nih.gov/pubmed/17897670" ], "ideal_answer": [ "The genus and species of the European honey bee is Apis mellifera." ], "exact_answer": [ "Apis" ], "type": "factoid", "id": "58e23ec66fddd3e83e000010", "snippets": [ { "offsetInBeginSection": 52, "offsetInEndSection": 87, "text": "European honey bee (Apis mellifera)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447542", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 106, "text": " European honey bees (Apis mellifera)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18941909", "endSection": "title" }, { "offsetInBeginSection": 63, "offsetInEndSection": 99, "text": " European honey bees (Apis mellifera", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17897670", "endSection": "title" }, { "offsetInBeginSection": 56, "offsetInEndSection": 92, "text": " European honey bees, Apis mellifera", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17897670", "endSection": "abstract" } ] }, { "body": "Where is the TAZ (G4.5) is located in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9345098", "http://www.ncbi.nlm.nih.gov/pubmed/25118650", "http://www.ncbi.nlm.nih.gov/pubmed/23398819", "http://www.ncbi.nlm.nih.gov/pubmed/12032589", "http://www.ncbi.nlm.nih.gov/pubmed/23606313", "http://www.ncbi.nlm.nih.gov/pubmed/19261493", "http://www.ncbi.nlm.nih.gov/pubmed/11735032", "http://www.ncbi.nlm.nih.gov/pubmed/23031367", "http://www.ncbi.nlm.nih.gov/pubmed/10407787" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1336578", "o": "http://linkedlifedata.com/resource/umls/label/A20729485" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20729485", "o": "TAZ gene" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1336578", "o": "http://linkedlifedata.com/resource/umls/label/A6916046" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6916046", "o": "TAZ gene" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0086418", "o": "http://linkedlifedata.com/resource/umls/label/A6958822" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1336578", "o": "http://linkedlifedata.com/resource/umls/label/A20747487" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20747487", "o": "G4.5" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1336578", "o": "TAZ" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0086418", "o": "Man" } ], "ideal_answer": [ "TAZ gene (G4.5) is located on Xq28 in humans." ], "exact_answer": [ "Xq28" ], "concepts": [ "http://www.uniprot.org/uniprot/TAZ_MACMU", "http://www.uniprot.org/uniprot/TAZ_HUMAN", "http://www.uniprot.org/uniprot/TAZ_SAISC", "http://www.uniprot.org/uniprot/TAZ_PONPY", "http://www.uniprot.org/uniprot/TAZ_ERYPA", "http://www.uniprot.org/uniprot/TAZ_PANTR", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801" ], "type": "factoid", "id": "58d906b28acda3452900000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Tafazzin (EC 2.3.1.23) is a Phospholipid Transacylase involved in Cardiolipin remodeling on mitochondrial membrane and coded by TAZ gene (Cytogenetic Location: Xq28) in human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25118650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Barth syndrome is an X-linked cardiomyopathy with neutropenia and 3-methylglutaconic aciduria. Recently, mutations in the G4.5 gene, located in Xq28, have been described in four probands with Barth syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9345098", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 294, "text": "The disorder is caused by mutations in the tafazzin (TAZ/G4.5) gene located on Xq28.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23606313", "endSection": "abstract" }, { "offsetInBeginSection": 1506, "offsetInEndSection": 1702, "text": "Disabling mutations or deletions of the tafazzin (TAZ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The tafazzin gene (TAZ) is located at Xq28 and encodes a protein involved in the transacylation of cardiolipin, an essential mitochondrial phospholipid", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23031367", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 294, "text": "The disorder is caused by mutations in the tafazzin (TAZ/G4.5) gene located on Xq28", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23606313", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 295, "text": "The disorder is caused by mutations in the tafazzin (TAZ/G4.5) gene located on Xq28.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23606313", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 207, "text": "Recently, mutations in the G4.5 gene, located in Xq28, have been described in four probands with Barth syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9345098", "endSection": "abstract" } ] }, { "body": "What do nerve-associated peripheral glial progenitors give rise to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24925909" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0027757", "o": "NERVE" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0027757", "o": "http://linkedlifedata.com/resource/umls/label/A20241247" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20241247", "o": "NERVE" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0027740", "o": "http://linkedlifedata.com/resource/umls/label/A0006429" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0006429", "o": "Nerve" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0027740", "o": "http://linkedlifedata.com/resource/umls/label/A0006426" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0006426", "o": "Nerve" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0205100", "o": "Peripheral" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0205100", "o": "http://linkedlifedata.com/resource/umls/label/A20244302" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0027740", "o": "Nerves" } ], "ideal_answer": [ "Nerve-associated peripheral glial progenitors give rise to parasympathetic neurons. The parasympathetic system in mice--including trunk ganglia and the cranial ciliary, pterygopalatine, lingual, submandibular, and otic ganglia--arise from glial cells in nerves, not neural crest cells. The parasympathetic fate is induced in nerve-associated Schwann cell precursors at distal peripheral sites.", "Parasympathetic neurons originate from nerve-associated peripheral glial progenitors. The parasympathetic fate is induced in nerve-associated Schwann cell precursors at distal peripheral sites.", "Parasympathetic neurons originate from nerve-associated peripheral glial progenitors." ], "exact_answer": [ "Parasympathetic neurons" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009457", "http://amigo.geneontology.org/amigo/term/GO:0010001", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009417", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009474" ], "type": "factoid", "id": "5881f9b65bf093691f000001", "snippets": [ { "offsetInBeginSection": 18, "offsetInEndSection": 103, "text": "Parasympathetic neurons originate from nerve-associated peripheral glial progenitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925909", "endSection": "title" }, { "offsetInBeginSection": 156, "offsetInEndSection": 478, "text": "We show that the parasympathetic system in mice--including trunk ganglia and the cranial ciliary, pterygopalatine, lingual, submandibular, and otic ganglia--arise from glial cells in nerves, not neural crest cells. The parasympathetic fate is induced in nerve-associated Schwann cell precursors at distal peripheral sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Neurodevelopment. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925909", "endSection": "title" }, { "offsetInBeginSection": 18, "offsetInEndSection": 102, "text": "Parasympathetic neurons originate from nerve-associated peripheral glial progenitors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925909", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Neurodevelopment. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925909", "endSection": "title" } ] }, { "body": "How many topological associated domains are contained in the human Hox cluster?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24843030" ], "ideal_answer": [ "transcriptional activation is associated with a dynamic bi-modal 3d organization, whereby the genes switch autonomously from an inactive to an active compartment.", "Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. ", ", hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. . activation is associated with a dynamic bi-modal 3d organization , whereby the genes switch autonomously from an inactive to an active compartment. . ", "Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment." ], "exact_answer": [ "two", "2" ], "type": "factoid", "id": "58e793f53e8b6dc87c000008", "snippets": [ { "offsetInBeginSection": 422, "offsetInEndSection": 543, "text": "Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24843030", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 706, "text": "Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24843030", "endSection": "abstract" } ] }, { "body": "Is Lennox-Gastaut Syndrome usually diagnosed in older adults?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22576075", "http://www.ncbi.nlm.nih.gov/pubmed/8029151", "http://www.ncbi.nlm.nih.gov/pubmed/19588340", "http://www.ncbi.nlm.nih.gov/pubmed/26166587", "http://www.ncbi.nlm.nih.gov/pubmed/24659735", "http://www.ncbi.nlm.nih.gov/pubmed/20542434", "http://www.ncbi.nlm.nih.gov/pubmed/26945476", "http://www.ncbi.nlm.nih.gov/pubmed/9400037", "http://www.ncbi.nlm.nih.gov/pubmed/20518600" ], "ideal_answer": [ "lennox-gastaut syndrome (lgs) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 hz) spike wave discharges on electroencephalography.", " children with Lennox-Gastaut syndrome Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 Hz) spike wave discharges on electroencephalography", "Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 Hz) spike wave discharges on electroencephalography." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050561", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065768" ], "type": "yesno", "id": "58dbb4f08acda3452900001a", "snippets": [ { "offsetInBeginSection": 583, "offsetInEndSection": 729, "text": "We studied 15 LGS patients (mean age \u00b1 1 standard deviation [SD] = 28.7 \u00b1 10.6 years) and 17 healthy controls (mean age \u00b1 1 SD = 27.6 \u00b1 6.6 years)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26945476", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 129, "text": " children with Lennox-Gastaut syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24659735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 Hz) spike wave discharges on electroencephalography", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26166587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Clinical course and results of therapy were analysed in the group of 92 children, aged between 3 and 9 years, with diagnosed Lennox-Gastaut syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8029151", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 659, "text": "We report the case of a 27-year-old man with a neurodevelopmental syndrome due to a 15q duplication, with intellectual disability, psychiatric disturbances, and an epileptic phenotype diagnosed as late-onset Lennox-Gastaut syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22576075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Lennox-Gastaut syndrome is a relatively rare epilepsy syndrome that usually begins in early-mid childhood and is characterized by multiple seizure types, particularly generalized seizures, which are often resistant to antiepileptic drug medication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20518600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Lennox-Gastaut Syndrome is a severe childhood epilepsy syndrome characterised by the diagnostic triad of a slow spike and wave pattern on electroencephalogram, multiple seizure types and developmental delay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20542434", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 660, "text": "We report the case of a 27-year-old man with a neurodevelopmental syndrome due to a 15q duplication, with intellectual disability, psychiatric disturbances, and an epileptic phenotype diagnosed as late-onset Lennox-Gastaut syndrome..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22576075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The Lennox-Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9400037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Lennox-Gastaut syndrome is a relatively rare epilepsy syndrome that usually begins in early-mid childhood and is characterized by multiple seizure types, particularly generalized seizures, which are often resistant to antiepileptic drug medication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20518600", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 400, "text": "The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behaviour disorders. It occurs more frequently in males and onset is usually before the age of eight, with a peak between three and five years. Late cases occurring in adolescence and early adulthood have rarely been reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19588340", "endSection": "abstract" } ] }, { "body": "Which treatment methods were compared in the EXCEL Trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21796086", "http://www.ncbi.nlm.nih.gov/pubmed/25983143", "http://www.ncbi.nlm.nih.gov/pubmed/26159652", "http://www.ncbi.nlm.nih.gov/pubmed/27639738", "http://www.ncbi.nlm.nih.gov/pubmed/21547994", "http://www.ncbi.nlm.nih.gov/pubmed/22941121", "http://www.ncbi.nlm.nih.gov/pubmed/22075415", "http://www.ncbi.nlm.nih.gov/pubmed/25583761", "http://www.ncbi.nlm.nih.gov/pubmed/22511269", "http://www.ncbi.nlm.nih.gov/pubmed/23995725" ], "ideal_answer": [ "EXCEL trial compared Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization." ], "exact_answer": [ [ "Everolimus Eluting Stent" ], [ "Coronary Artery Bypass Surgery" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017428", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017326", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430" ], "type": "list", "id": "5880b583c872c95565000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Long-term forecasting and comparison of mortality in the Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial: prospective validation of the SYNTAX Score II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583761", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "AIMS: To prospectively validate the SYNTAX Score II and forecast the outcomes of the randomized Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583761", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1665, "text": "Based on 4-year mortality predictions in EXCEL, clinical characteristics shifted long-term mortality predictions either in favour of PCI (older age, male gender and COPD) or CABG (younger age, lower creatinine clearance, female gender, reduced left ventricular ejection fraction).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583761", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 797, "text": "Given that the completed randomized trials did not include contemporary DESs, the upcoming results of the ongoing trials evaluating the performance of new-generation DES compared with CABG (such as the EXCEL trial), may further help to clarify the current role and future recommendations of PCI for left main coronary artery disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26159652", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 686, "text": "The ongoing EXCEL trial will help elucidate the role of ULMCA PCI in the treatment of left main disease compared with coronary artery bypass graft surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23995725", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1412, "text": "The ongoing Evaluation of XIENCE V Everolimus Eluting Stent System Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is expected to provide a better answer on the optimal treatment strategy for LMCAD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22941121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "The Evaluation of Xience Prime or Xience V versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is a multicenter, ongoing trial conducted in patients with left main disease and SYNTAX score \u2264 32 to establish the presumptive advantage of percutaneous coronary intervention (PCI) versus bypass surgery in patients with less complex coronary artery disease than those enrolled in the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075415", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1095, "text": "The EXCEL trial will address the value of PCI in relation to CABG for the treatment of ULMCA stenosis in more than 2000 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22511269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 478, "text": "OBJECTIVES: The aim of this study is to verify the study hypothesis of the EXCEL trial by comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in an EXCEL-like population of patients.BACKGROUND: The upcoming EXCEL trial will test the hypothesis that left main patients with SYNTAX score \u2264 32 experience similar rates of 3-year death, myocardial infarction (MI), or cerebrovascular accidents (CVA) following revascularization by PCI or CABG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21547994", "endSection": "abstract" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1562, "text": "CONCLUSIONS: In an EXCEL-like cohort of patients with left main disease, there seems to be a clinical equipoise between PCI and CABG in terms of death/MI/CVA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21547994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The aim of this study is to verify the study hypothesis of the EXCEL trial by comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in an EXCEL-like population of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21547994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 730, "text": "To prospectively validate the SYNTAX Score II and forecast the outcomes of the randomized Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Trial.Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization is a prospective, randomized multicenter trial designed to establish the efficacy and safety of percutaneous coronary intervention (PCI) with the everolimus-eluting stent compared with coronary artery bypass graft (CABG) surgery in subjects with unprotected left-main coronary artery (ULMCA) disease and low-intermediate anatomical SYNTAX scores (<33).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "OBJECTIVES: The aim of this study is to verify the study hypothesis of the EXCEL trial by comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in an EXCEL-like population of patients.BACKGROUND: The upcoming EXCEL trial will test the hypothesis that left main patients with SYNTAX score ?", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21547994", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 902, "text": "The results of the ongoing EXCEL trial, which compares left main percutaneous coronary intervention with drug-eluting stents and CABG, will provide insight regarding the ideal revascularization strategy for these patients..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21796086", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 796, "text": "Given that the completed randomized trials did not include contemporary DESs, the upcoming results of the ongoing trials evaluating the performance of new-generation DES compared with CABG (such as the EXCEL trial), may further help to clarify the current role and future recommendations of PCI for left main coronary artery disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26159652", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 904, "text": "The introduction of the newer-generation drug-eluting stents (DES) -with documented improvements in both safety and efficacy- has prompted the interventional community to design two new dedicated randomised trials comparing CABG and PCI: the NOBLE (Coronary Artery Bypass Grafting Vs Drug Eluting Stent Percutaneous Coronary Angioplasty in the Treatment of Unprotected Left Main Stenosis) and EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25983143", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1094, "text": "The EXCEL trial will address the value of PCI in relation to CABG for the treatment of ULMCA stenosis in more than 2000 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22511269", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1368, "text": "The ongoing Evaluation of XIENCE V Everolimus Eluting Stent System Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is expected to provide a better answer on the optimal treatment strategy for LMCAD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22941121", "endSection": "abstract" } ] }, { "body": "Describe ATR-16 syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9375730", "http://www.ncbi.nlm.nih.gov/pubmed/24631100", "http://www.ncbi.nlm.nih.gov/pubmed/10631133", "http://www.ncbi.nlm.nih.gov/pubmed/8606626", "http://www.ncbi.nlm.nih.gov/pubmed/17598130", "http://www.ncbi.nlm.nih.gov/pubmed/10872473", "http://www.ncbi.nlm.nih.gov/pubmed/8460633", "http://www.ncbi.nlm.nih.gov/pubmed/15921166", "http://www.ncbi.nlm.nih.gov/pubmed/18076105" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0795917", "o": "http://linkedlifedata.com/resource/umls/label/A11992244" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11992244", "o": "ATR-16 SYNDROME" } ], "ideal_answer": [ "ATR-16 syndrome is due to alterations on chromosome 16p13.3, and is usually accompanied by alpha-thalassemia, mild-moderate mental retardation, dysmorphic facial features, skeletal and genitourinary malformations." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225" ], "type": "summary", "id": "588623153b87a8a738000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "ATR-16 syndrome is due to alterations on chromosome 16p13.3, and is usually accompanied by alpha-thalassemia, mild-moderate mental retardation, dysmorphic facial features, skeletal and genitourinary malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24631100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Alpha thalassemia retardation associated with chromosome16 (ATR-16 syndrome) is defined as a contiguous gene syndrome resulting from haploinsufficiency of the alpha-globin gene cluster and genes involved in mental retardation (MR). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17598130", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 652, "text": "This is the fifth reported case of the ATR-16 syndrome (alpha-thalassemia retardation-16) not complicated by duplication or deletion of other chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9375730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Familial mental retardation syndrome ATR-16 due to an inherited cryptic subtelomeric translocation, t(3;16)(q29;p13.3).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10631133", "endSection": "title" } ] }, { "body": "What is the results of inactivated ANGPLT3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24798233", "http://www.ncbi.nlm.nih.gov/pubmed/22062970" ], "ideal_answer": [ "Complete ANGPTL3 deficiency caused by loss-of-function mutations of ANGPTL3 is associated with a recessive hypolipidemia" ], "exact_answer": [ "Recessive hypolipidemia" ], "type": "factoid", "id": "58dfd70c6fddd3e83e000002", "snippets": [ { "offsetInBeginSection": 681, "offsetInEndSection": 895, "text": "Although it appears by now that the main lipid pathways have been uncovered, and that only modulators or adaptor proteins such as those encoded by LDLRAP1, APOA5, ANGPLT3/4, and PCSK9 are currently being discovered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798233", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 355, "text": "Angptl3 knockout mice have marked hypolipidemia, and heterozygous carriers of ANGPLT3, loss-of-function mutations were found among individuals in the lowest quartile of plasma triglycerides in population studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22062970", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 493, "text": " 4 related individuals with primary hypolipidemia were found to be compound heterozygotes for ANGPTL3 loss-of-function mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22062970", "endSection": "abstract" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 1823, "text": "Complete ANGPTL3 deficiency caused by loss-of-function mutations of ANGPTL3 is associated with a recessive hypolipidemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22062970", "endSection": "abstract" } ] }, { "body": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22044414", "http://www.ncbi.nlm.nih.gov/pubmed/24040234" ], "ideal_answer": [ "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. ", "The introduction of anti-TNF therapy has dramatically improved the outlook for patients suffering from a number of inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients.", "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. A substantial proportion of Rheumatoid Arthritis patients (approximately 30-40%) fail to respond to anti-TNF therapies.", "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients.", "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. ", "strategies blocking tumor necrosis factor (anti-tnf) have proven very successful in patients with rheumatoid arthritis (ra) , showing beneficial effects in approximately 50-60% of the patients. . this , a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies . ", "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. The introduction of anti-TNF therapy has dramatically improved the outlook for patients suffering from a number of inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease.", "treatment strategies blocking tumor necrosis factor (anti-tnf) have proven very successful in patients with rheumatoid arthritis (ra), showing beneficial effects in approximately 50-60% of the patients.", "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. ", "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients.", "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies." ], "exact_answer": [ "50-60%" ], "type": "factoid", "id": "58e79e703e8b6dc87c00000a", "snippets": [ { "offsetInBeginSection": 202, "offsetInEndSection": 344, "text": "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22044414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040234", "endSection": "abstract" } ] }, { "body": "Which disease is treated with semaglutide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22675341", "http://www.ncbi.nlm.nih.gov/pubmed/26308095", "http://www.ncbi.nlm.nih.gov/pubmed/27432074", "http://www.ncbi.nlm.nih.gov/pubmed/26694823", "http://www.ncbi.nlm.nih.gov/pubmed/27183953", "http://www.ncbi.nlm.nih.gov/pubmed/27817160", "http://www.ncbi.nlm.nih.gov/pubmed/27921428", "http://www.ncbi.nlm.nih.gov/pubmed/27863704", "http://www.ncbi.nlm.nih.gov/pubmed/27835045", "http://www.ncbi.nlm.nih.gov/pubmed/25475122", "http://www.ncbi.nlm.nih.gov/pubmed/26642233", "http://www.ncbi.nlm.nih.gov/pubmed/27042424", "http://www.ncbi.nlm.nih.gov/pubmed/26358288", "http://www.ncbi.nlm.nih.gov/pubmed/27633186" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0049608" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "Disease" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/1022004", "o": "http://linkedlifedata.com/resource/rxnorm/label/3147522" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3147522", "o": "Disease" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A18683747" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18683747", "o": "disease" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0015569" } ], "ideal_answer": [ "Semaglutide is glucagon-like peptide-1 receptor agonist that is being used for the treatment of type 2 diabetes mellitus." ], "exact_answer": [ "Type 2 diabetes mellitus", "TYPE 2 DIABETES" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019468" ], "type": "factoid", "id": "5880c42fc872c95565000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 741, "text": "INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the treatment of type 2 diabetes mellitus, but consideration of benefits and potential adverse events is required. This review examines the state of glycemic control, weight loss, blood pressure, and tolerability, as well as the current debate about the safety of GLP-1 RAs, including risk of pancreatitis, pancreatic cancer, and thyroid cancer.METHODS: A MEDLINE search (2010-2015) identified publications that discussed longer-acting GLP-1 RAs. Search terms included GLP-1 receptor agonists, liraglutide, exenatide, lixisenatide, semaglutide, dulaglutide, albiglutide, efficacy, safety, pancreatitis, pancreatic cancer, and thyroid cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26694823", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 872, "text": " Seven trials have been published that have established CV safety for three DPP-4 inhibitors (alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists (liraglutide, lixisenatide, and semaglutide), and one sodium-glucose cotransporter-2 inhibitor (empagliflozin). Three of those studies also established superiority with liraglutide, empagliflozin, and semaglutide at reducing the composite primary endpoint of major CV events (CV death, nonfatal myocardial infarction, and nonfatal stroke). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27835045", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 727, "text": "RECENT FINDINGS: In response to guidance issued by the Food and Drug Administration, thousands of patients have been enrolled in large randomized trials evaluating the cardiovascular effects of the three newest diabetes drug classes: glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Two studies of GLP-1 receptor agonists-one of liraglutide and one of semaglutide-have shown cardiovascular benefit relative to placebo, and one study of the SGLT-2 inhibitor empagliflozin has shown benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27817160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "New antidiabetic drugs are being developed today that expand the range of pharmacological intervention, in particular for patients with type 2 diabetes (imeglimin, semaglutide, dulaglutide, FGF 21 analogue).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27921428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25475122", "endSection": "abstract" }, { "offsetInBeginSection": 2040, "offsetInEndSection": 2365, "text": "Conclusions In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27633186", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 526, "text": "Postmenopausal women with T2D (n\u2009=\u200943) on diet/exercise\u2009\u00b1\u2009metformin received ethinylestradiol (0.03\u2009mg)/levonorgestrel (0.15\u2009mg) once daily for 8 days before (semaglutide-free) and during (steady-state 1.0\u2009mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25\u2009mg 4 weeks; 0.5\u2009mg 4 weeks; 1.0\u2009mg 5 weeks).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25475122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27633186", "endSection": "title" } ] }, { "body": "What condition is usually represented by the acronym SUDEP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19623466", "http://www.ncbi.nlm.nih.gov/pubmed/25323494", "http://www.ncbi.nlm.nih.gov/pubmed/23099115", "http://www.ncbi.nlm.nih.gov/pubmed/19713869", "http://www.ncbi.nlm.nih.gov/pubmed/22042178", "http://www.ncbi.nlm.nih.gov/pubmed/25499158", "http://www.ncbi.nlm.nih.gov/pubmed/22191982", "http://www.ncbi.nlm.nih.gov/pubmed/19666211", "http://www.ncbi.nlm.nih.gov/pubmed/23109241", "http://www.ncbi.nlm.nih.gov/pubmed/19909334", "http://www.ncbi.nlm.nih.gov/pubmed/25253292", "http://www.ncbi.nlm.nih.gov/pubmed/17433051", "http://www.ncbi.nlm.nih.gov/pubmed/24348119", "http://www.ncbi.nlm.nih.gov/pubmed/25600783", "http://www.ncbi.nlm.nih.gov/pubmed/23962523", "http://www.ncbi.nlm.nih.gov/pubmed/26387918", "http://www.ncbi.nlm.nih.gov/pubmed/27131289", "http://www.ncbi.nlm.nih.gov/pubmed/15824334", "http://www.ncbi.nlm.nih.gov/pubmed/19232547", "http://www.ncbi.nlm.nih.gov/pubmed/25647769", "http://www.ncbi.nlm.nih.gov/pubmed/26038597", "http://www.ncbi.nlm.nih.gov/pubmed/17178458", "http://www.ncbi.nlm.nih.gov/pubmed/12862502", "http://www.ncbi.nlm.nih.gov/pubmed/26924854", "http://www.ncbi.nlm.nih.gov/pubmed/19130900", "http://www.ncbi.nlm.nih.gov/pubmed/24139807", "http://www.ncbi.nlm.nih.gov/pubmed/24236903", "http://www.ncbi.nlm.nih.gov/pubmed/16421121", "http://www.ncbi.nlm.nih.gov/pubmed/21737136", "http://www.ncbi.nlm.nih.gov/pubmed/15129839" ], "ideal_answer": [ "The acronym SUDEP refers to Sudden Unexpected Death in Epilepsy", "Sudden Unexpected Death in Epilepsy (SUDEP). sudden unexpected death in epilepsy (SUDEP),. ", " sudden unexpected death in epilepsy (SUDEP), Sudden Unexpected Death in Epilepsy (SUDEP)", "Sudden Unexpected Death in Epilepsy (SUDEP)" ], "exact_answer": [ "Sudden Unexpected Death in Epilepsy (SUDEP)" ], "type": "factoid", "id": "58dbb8968acda3452900001b", "snippets": [ { "offsetInBeginSection": 117, "offsetInEndSection": 160, "text": "Sudden Unexpected Death in Epilepsy (SUDEP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26038597", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 211, "text": " sudden unexpected death in epilepsy (SUDEP),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26387918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Sudden unexpected death in epilepsy (SUDEP) is the most important direct seizure-related cause of death, and most cases usually occur in patients with intractable, longstanding epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19232547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Sudden unexpected death in epilepsy (SUDEP): what do patients think?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25499158", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25499158", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 582, "text": "In 11 patients cause of death was sudden unexpected death in epilepsy (SUDEP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22042178", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 334, "text": "Epilepsy-related death, particularly sudden unexpected death in epilepsy (SUDEP), is still underestimated by healthcare professionals and this may reflect the mistaken belief that epilepsy is a benign condition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23962523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Risk factors in sudden death in epilepsy (SUDEP): the quest for mechanisms", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17433051", "endSection": "title" }, { "offsetInBeginSection": 89, "offsetInEndSection": 296, "text": "Sudden unexpected death in epilepsy (SUDEP) is a - probably heterogeneous - condition where patients with epilepsy die suddenly, almost certainly during a seizure and with no other identified cause of death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24236903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Epilepsy, the commonest serious neurological condition, is associated with an increased risk in premature deaths, including an estimated 500 sudden unexpected deaths (SUDEP) per year in the UK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15129839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19623466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Sudden unexpected death in epilepsy (SUDEP) is an exceptionally difficult condition to study in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24348119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Sudden unexpected death in epilepsy (SUDEP): don't ask, don't tell?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16421121", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 276, "text": "Many individuals with epilepsy, as well as their partners, relatives, and friends, are unaware of the risk for sudden unexpected death in epilepsy (SUDEP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19909334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26924854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Sudden unexpected death in epilepsy (SUDEP) refers to the sudden death of a seemingly healthy individual with epilepsy, usually occurring during, or immediately after, a tonic-clonic seizure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737136", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 236, "text": "This condition is called sudden unexpected death in epilepsy (SUDEP), and it accounts for a large proportion of deaths among people with epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19713869", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 335, "text": "Epilepsy-related death, particularly sudden unexpected death in epilepsy (SUDEP), is still underestimated by healthcare professionals and this may reflect the mistaken belief that epilepsy is a benign condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23962523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Sudden unexpected death in epilepsy (SUDEP) i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22191982", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 130, "text": " sudden unexpected death in epilepsy (SUDEP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19130900", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 70, "text": "sudden unexpected death in epilepsy (SUDEP) f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600783", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 44, "text": "udden unexpected death in epilepsy (SUDEP) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12862502", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 88, "text": "sudden and unexpected death in epilepsy (SUDEP) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17178458", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 53, "text": "Sudden unexpected death in epilepsy (SUDEP) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25647769", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 113, "text": "sudden unexpected death in epilepsy (SUDEP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824334", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 45, "text": "udden unexpected death in epilepsy (SUDEP) i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25323494", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 53, "text": "Sudden unexplained death in epilepsy (SUDEP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099115", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 44, "text": "udden unexpected death in epilepsy (SUDEP) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24139807", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 201, "text": " sudden unexpected death in epilepsy (SUDEP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23109241", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 105, "text": "udden unexpected death in epilepsy (SUDEP) is the leading cause for death in individuals with epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27131289", "endSection": "abstract" } ] }, { "body": "Which proteins does the yeast Cleavage and Polyadenylation Complex contain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12773397", "http://www.ncbi.nlm.nih.gov/pubmed/15659578", "http://www.ncbi.nlm.nih.gov/pubmed/23514951", "http://www.ncbi.nlm.nih.gov/pubmed/25877920", "http://www.ncbi.nlm.nih.gov/pubmed/18951092", "http://www.ncbi.nlm.nih.gov/pubmed/20226668", "http://www.ncbi.nlm.nih.gov/pubmed/19049464" ], "ideal_answer": [ "The proteins Nrd1, Rap1, Trf4, Rrp6, Ssu72, Cstf64, Pcf11 and PAP are the major components of the 3' cleavage and polyadenylation complex." ], "exact_answer": [ [ "Nrd1" ], [ "Rap1" ], [ "Trf4" ], [ "Rrp6" ], [ "Ssu72" ], [ "PAP" ], [ "Cstf64" ], [ "Pcf11" ] ], "type": "list", "id": "58add7699ef3c34033000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Gene loops have been described in different organisms from yeast to human and form through interaction between components of the transcription pre-initiation complex and Ssu72, a member of the 3' end cleavage and polyadenylation complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23514951", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 364, "text": "A large cleavage and polyadenylation complex containing the major poly(A) polymerase Pap1 produces mRNA 3' ends, whereas those of nonpolyadenylated snoRNAs in yeast are formed either by endonucleolytic cleavage or by termination, followed by trimming by the nuclear exosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18951092", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 814, "text": "Poly(A) tails are added by Pap1 to both forms, whereas the alternative poly(A) polymerase Tfr4 adenylates major precursors and processing intermediates to facilitate further polyadenylation by Pap1 and maturation by the exosome/Rrp6", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18951092", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 911, "text": "A more important role of Trf4/TRAMP, however, is to enhance Nrd1 association with snoRNA genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18951092", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 844, "text": "Screening crude natural product extracts with this technology has resulted in the identification of a novel family of antifungal natural products, named the parnafungins, which inhibit the enzyme polyadenosine polymerase (PAP), a key component of the mRNA cleavage and polyadenylation complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19049464", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 884, "text": "We show that phosphorylation of TFIIB at serine 65 regulates the interaction between TFIIB and the CstF-64 component of the CstF 3' cleavage and polyadenylation comple", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20226668", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 400, "text": "We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termination through the action of its C-terminal domain (CTD)-interacting domain (CID)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25877920", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 560, "text": "Like the yeast counterpart, mammalian Ssu72 associates with TFIIB and the yeast cleavage/polyadenylation factor Pta1, and exhibits intrinsic phosphatase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15659578", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 772, "text": "We also provide evidence that Pti1p probably acts by uncoupling cleavage and polyadenylation, and functions in coordination with the Nrd1p-dependent pathway for 3' end formation of non-polyadenylated transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12773397", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 562, "text": "Like the yeast counterpart, mammalian Ssu72 associates with TFIIB and the yeast cleavage/polyadenylation factor Pta1, and exhibits intrinsic phosphatase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15659578", "endSection": "abstract" } ] }, { "body": "Which disease can be categorized using the Koos grading system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26967786", "http://www.ncbi.nlm.nih.gov/pubmed/25811349", "http://www.ncbi.nlm.nih.gov/pubmed/26606668", "http://www.ncbi.nlm.nih.gov/pubmed/25181431", "http://www.ncbi.nlm.nih.gov/pubmed/27513938", "http://www.ncbi.nlm.nih.gov/pubmed/24797568", "http://www.ncbi.nlm.nih.gov/pubmed/15179293", "http://www.ncbi.nlm.nih.gov/pubmed/21665381", "http://www.ncbi.nlm.nih.gov/pubmed/23160632", "http://www.ncbi.nlm.nih.gov/pubmed/27453796", "http://www.ncbi.nlm.nih.gov/pubmed/24987677" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0049608" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0049608", "o": "Disease" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/1022004", "o": "http://linkedlifedata.com/resource/rxnorm/label/3147522" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3147522", "o": "Disease" } ], "ideal_answer": [ "Koos grading system is used for vestibular schwannoma." ], "exact_answer": [ "vestibular schwannoma" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category" ], "type": "factoid", "id": "5886519c3b87a8a738000007", "snippets": [ { "offsetInBeginSection": 636, "offsetInEndSection": 789, "text": "The patients had Koos Grade I or II tumors and American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Class D hearing status preoperatively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26967786", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 378, "text": "METHODS: This is a retrospective review of 22 patients with VS Koos grade III and IV who were treated with STR followed by SRS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27513938", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 585, "text": " VS was characterized by its size (Koos classification) and the presence or not of a cystic component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25811349", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 788, "text": "MAIN OUTCOME MEASURES: All data recorded were reviewed to access age, sex, tumor type, and tumor size according to the Koos classification and presenting symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24797568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Facial nerve preservation surgery for koos grade 3 and 4 vestibular schwannomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25181431", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Safety and Efficacy of Gamma Knife Radiosurgery for the Management of Koos Grade 4 Vestibular Schwannomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26606668", "endSection": "title" }, { "offsetInBeginSection": 368, "offsetInEndSection": 509, "text": "In all 333 patients microsurgical vestibular schwannoma (Koos grade 1: 12, grade 2: 34, grade 3: 62, and grade 4: 225) removal was performed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24987677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Facial nerve preservation surgery for koos grade 3 and 4 vestibular schwannomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25181431", "endSection": "title" }, { "offsetInBeginSection": 195, "offsetInEndSection": 293, "text": "To report, in a retrospective study, outcomes for large Koos grade 3 and 4 vestibular schwannomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25181431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Safety and Efficacy of Gamma Knife Radiosurgery for the Management of Koos Grade 4 Vestibular Schwannomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26606668", "endSection": "title" } ] }, { "body": "What is the inheritance of the glucose-6-phosphate dehydrogenase (G6PD) deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25116429", "http://www.ncbi.nlm.nih.gov/pubmed/1188317", "http://www.ncbi.nlm.nih.gov/pubmed/6350992", "http://www.ncbi.nlm.nih.gov/pubmed/15226563", "http://www.ncbi.nlm.nih.gov/pubmed/26275698", "http://www.ncbi.nlm.nih.gov/pubmed/12169625", "http://www.ncbi.nlm.nih.gov/pubmed/24460025", "http://www.ncbi.nlm.nih.gov/pubmed/631693", "http://www.ncbi.nlm.nih.gov/pubmed/24865682", "http://www.ncbi.nlm.nih.gov/pubmed/11261779", "http://www.ncbi.nlm.nih.gov/pubmed/10066026", "http://www.ncbi.nlm.nih.gov/pubmed/1634454", "http://www.ncbi.nlm.nih.gov/pubmed/10698963", "http://www.ncbi.nlm.nih.gov/pubmed/24943486", "http://www.ncbi.nlm.nih.gov/pubmed/11271380", "http://www.ncbi.nlm.nih.gov/pubmed/1953691", "http://www.ncbi.nlm.nih.gov/pubmed/12737943" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/uniprot/P11413", "o": "http://purl.uniprot.org/uniprot/P11413" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0017757", "o": "G6PD" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_503131343133004B", "o": "G6PD" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0017757", "o": "http://linkedlifedata.com/resource/umls/label/A8256485" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://linkedlifedata.com/resource/drugbank/molecule/1799", "o": "http://purl.uniprot.org/uniprot/P11413" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/drugbank/molecule/1799", "o": "Glucose-6-phosphate 1-dehydrogenase" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/uniprot/P11413", "o": "G6PD_HUMAN" } ], "ideal_answer": [ "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has a recessive X-linked inheritance." ], "exact_answer": [ "recessive X-linked inheritance" ], "concepts": [ "http://www.uniprot.org/uniprot/G6PD_BUCAI", "http://www.disease-ontology.org/api/metadata/DOID:2862", "http://www.uniprot.org/uniprot/G6PD_CERCA", "http://www.uniprot.org/uniprot/G6PD_CRIGR", "http://www.uniprot.org/uniprot/G6PD_EMENI", "http://www.uniprot.org/uniprot/G6PD_BUCAP", "http://www.uniprot.org/uniprot/G6PD_HUMAN", "http://www.uniprot.org/uniprot/G6PD_ZYMMO", "http://www.uniprot.org/uniprot/G6PD_MACRO", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042843", "http://www.uniprot.org/uniprot/G6PD_ENCCU", "http://www.uniprot.org/uniprot/G6PD_TAKRU", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005954", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005955", "http://www.uniprot.org/uniprot/G6PD_HAEIN", "http://www.uniprot.org/uniprot/G6PD_CYBJA", "http://www.uniprot.org/uniprot/G6PD_DIDVI", "http://www.uniprot.org/uniprot/G6PD_AGGAC", "http://www.uniprot.org/uniprot/G6PD_HELPY", "http://www.uniprot.org/uniprot/G6PD_BOSIN", "http://www.uniprot.org/uniprot/G6PD_GLUOX", "http://www.uniprot.org/uniprot/G6PD_HELPJ", "http://www.uniprot.org/uniprot/G6PD_NOSP7" ], "type": "factoid", "id": "58c6635f02b8c60953000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226563", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1317, "text": " The high manifestation of G6PD deficiency in women may be due to the preferential expression of the G6PD-deficient gene and X-inactivation of the normal gene, and/or to the presence of an 'enhancer' gene that makes the expression of the G6PD deficiency more likely. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10066026", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 605, "text": "Study of the deficiency pattern amongst family members of the enzyme deficient subjects confirmed the X-linked inheritance of G-6-PD deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1634454", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 639, "text": " The investigation of the patient's whole family showed the typical recessive X-linked inheritance of this enzyme-defect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6350992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "After having described in detail the pathophysiology, symptomatology, X-chromosomal inheritance and some laboratory methods in detecting G-6-PD-deficiency by demonstrating a case of favism (Schulz et al. 1977), the authors now discuss the particularities of the enzyme deficiency in the newborn. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/631693", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 327, "text": "The genetic pattern is consistent with x-linked recessive inheritance and the defect is associated with drug (primaquine) induced haemolysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1188317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "UNLABELLED: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder in which haemolytic anaemia is the major symptom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11271380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, and it has a significant prevalence in the male population (X chromosome linked).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15226563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by a mutation in the G6PD gene on Xq28.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275698", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 297, "text": "Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24943486", "endSection": "abstract" } ] }, { "body": "Which deep learning-based algorithms are used for enhancer prediction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "http://www.ncbi.nlm.nih.gov/pubmed/27929098", "http://www.ncbi.nlm.nih.gov/pubmed/26091399", "http://www.ncbi.nlm.nih.gov/pubmed/27490187", "http://www.ncbi.nlm.nih.gov/pubmed/27329130" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0086222", "o": "Enhancer" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0086222", "o": "http://linkedlifedata.com/resource/umls/label/A7570315" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7570315", "o": "Enhancer" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0205125", "o": "DEEP" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0205125", "o": "http://linkedlifedata.com/resource/umls/label/A20250446" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20250446", "o": "DEEP" } ], "ideal_answer": [ "EP-DNN and DEEP." ], "exact_answer": [ [ "EP-DNN" ], [ "DEEP" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069550" ], "type": "list", "id": "587d30fb31b33e8760000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27929098", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27929098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "DEEP: a general computational framework for predicting enhancers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "endSection": "title" }, { "offsetInBeginSection": 671, "offsetInEndSection": 1145, "text": " In this study we developed DEEP, a novel ensemble prediction framework. DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. In our method we train many individual classification models that we combine to classify DNA regions as enhancers or non-enhancers. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1080, "text": " in this paper, we use recent state-of-the-art Deep Learning methods and develop a deep neural network (DNN)-based architecture, called EP-DNN, to predict the presence and types of enhancers in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27490187", "endSection": "abstract" }, { "offsetInBeginSection": 2349, "offsetInEndSection": 2583, "text": "In this paper, we developed EP-DNN, which has high accuracy of prediction, with validation rates above 90\u00a0% for the operational region of enhancer prediction for all four cell lines that we studied, outperforming DEEP-ENCODE and RFECS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27490187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27929098", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 810, "text": "We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27929098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "PEDLA: predicting enhancers with a deep learning-based algorithmic framework.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27329130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "DEEP: a general computational framework for predicting enhancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378307", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "PEDLA: predicting enhancers with a deep learning-based algorithmic framework.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27329130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27929098", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 616, "text": "We developed a deep learning-based algorithmic framework named PEDLA (https://github.com/wenjiegroup/PEDLA), which can directly learn an enhancer predictor from massively heterogeneous data and generalize in ways that are mostly consistent across various cell types/tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27329130", "endSection": "abstract" } ] }, { "body": "Is Beta-Thalassemia is associated with a mutation or deletion of the gene that codes for alpha globin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9056561", "http://www.ncbi.nlm.nih.gov/pubmed/25230702" ], "ideal_answer": [ "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains", "beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains.", "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of -globin chains. ", "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055544", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017086" ], "type": "yesno", "id": "58dbbbf08acda3452900001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The beta-thalassemia syndromes are a heterogeneous group of genetic disorders characterized by reduced or absent expression of the beta-globin gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9056561", "endSection": "abstract" } ] }, { "body": "Is diphosphatidylglycerol (cardiolipin) a phospholipid of the mitochondrial membranes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21599656", "http://www.ncbi.nlm.nih.gov/pubmed/26028302", "http://www.ncbi.nlm.nih.gov/pubmed/24905496", "http://www.ncbi.nlm.nih.gov/pubmed/6717095", "http://www.ncbi.nlm.nih.gov/pubmed/4322761", "http://www.ncbi.nlm.nih.gov/pubmed/2397096", "http://www.ncbi.nlm.nih.gov/pubmed/6257342", "http://www.ncbi.nlm.nih.gov/pubmed/7794966", "http://www.ncbi.nlm.nih.gov/pubmed/3668386", "http://www.ncbi.nlm.nih.gov/pubmed/8143741", "http://www.ncbi.nlm.nih.gov/pubmed/23200781", "http://www.ncbi.nlm.nih.gov/pubmed/26301254", "http://www.ncbi.nlm.nih.gov/pubmed/6509920", "http://www.ncbi.nlm.nih.gov/pubmed/26396268", "http://www.ncbi.nlm.nih.gov/pubmed/6807345", "http://www.ncbi.nlm.nih.gov/pubmed/16971584", "http://www.ncbi.nlm.nih.gov/pubmed/9370332", "http://www.ncbi.nlm.nih.gov/pubmed/20336283", "http://www.ncbi.nlm.nih.gov/pubmed/24007978", "http://www.ncbi.nlm.nih.gov/pubmed/1213878", "http://www.ncbi.nlm.nih.gov/pubmed/9843887", "http://www.ncbi.nlm.nih.gov/pubmed/7459841", "http://www.ncbi.nlm.nih.gov/pubmed/3548756", "http://www.ncbi.nlm.nih.gov/pubmed/22634369", "http://www.ncbi.nlm.nih.gov/pubmed/7378435", "http://www.ncbi.nlm.nih.gov/pubmed/25182746", "http://www.ncbi.nlm.nih.gov/pubmed/3718705", "http://www.ncbi.nlm.nih.gov/pubmed/15460113", "http://www.ncbi.nlm.nih.gov/pubmed/25843549", "http://www.ncbi.nlm.nih.gov/pubmed/1550861", "http://www.ncbi.nlm.nih.gov/pubmed/24443516", "http://www.ncbi.nlm.nih.gov/pubmed/20637181", "http://www.ncbi.nlm.nih.gov/pubmed/8977117", "http://www.ncbi.nlm.nih.gov/pubmed/1247555", "http://www.ncbi.nlm.nih.gov/pubmed/24769127" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0202177", "o": "Phospholipid" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0007188", "o": "http://linkedlifedata.com/resource/umls/label/A17997459" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17997459", "o": "Cardiolipins" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/2083", "o": "http://linkedlifedata.com/resource/rxnorm/label/3130515" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3130515", "o": "Cardiolipins" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0007188", "o": "cardiolipin" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/2083", "o": "http://linkedlifedata.com/resource/rxnorm/label/3130514" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3130514", "o": "Cardiolipin" } ], "ideal_answer": [ "Yes, diphosphatidylglycerol (cardiolipin) is a phospholipid of the mitochondrial membranes." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002308", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008566", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008563", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4244279", "http://www.biosemantics.org/jochem#4001026", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008928", "http://www.biosemantics.org/jochem#4244279", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051336" ], "type": "yesno", "id": "58d90f228acda3452900000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24007978", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 474, "text": "A small decrease of diphosphatidylglycerol also occurred in the hepatoma mitochondria inner membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7459841", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 624, "text": "Diphosphatidylglycerol was confined to the mitochondrial fraction, where it represented about 7% of the total phosphoacylglycerols. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6807345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "Mitochondrial membranes were isolated from the myocardium of young (4-month-old) and aged (33-month-old) male Long-Evans rats and compared in terms of cholesterol content and phospholipid and fatty acid composition. In aged rats, as compared to young, the major observations include: markedly higher cholesterol content; increased percentage of sphingomyelin and diphosphatidylglycerol (cardiolipin); ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6717095", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 632, "text": "The polyglycerophosphatides (typified by diphosphatidylglycerol) were apparently synthesized in situ by intramitochondrial membrane-bound enzymes using CDP-diglycerides as intermediates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3548756", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 875, "text": "Both the mitochondrial and microsomal fractions contained significant proportions of solvent front phospholipid (SFP) and whereas the mitochondrial SFP displayed the relatively unsaturated fatty acid composition characteristic of diphosphatidylglycerol (cardiolipin), the fatty acids of the microsomal SFP were distinctly more saturated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6509920", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 764, "text": "Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3718705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "The enzyme responsible for the conversion of phosphatidylglycerol to diphosphatidylglycerol (cardiolipin) in the presence of cytidine diphosphate diacylglycerol is firmly associated with mitochondrial membranes and is not extracted with hypotonic or hypertonic media or with nonionic detergents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6257342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "The mechanism of cardiolipin (diphosphatidylglycerol) biosynthesis was examined in mitochondria and outer and inner mitochondrial membranes prepared from guinea pig and rat livers to determine whether this formation from phosphatidylglycerol was absolutely dependent on cytidinediphosphodiglyceride, as previously reported for intact mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2397096", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 597, "text": "In isolated mitochondrial outer membranes, cardiolipin (diphosphatidylglycerol) increased CPT1 activity 4-fold and the Km for carnitine 6-fold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21599656", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 765, "text": "Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3718705", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 615, "text": "90% or more of the phospholipid, cardiolipin was found in the mitochondrial membranes of wild type and petite yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4322761", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 760, "text": "Furthermore, the same mechanism for the biosynthesis of cardiolipin was operational in the outer and inner mitochondrial membranes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2397096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "The mechanism of cardiolipin (diphosphatidylglycerol) biosynthesis was examined in mitochondria and outer and inner mitochondrial membranes prepared from guinea pig and rat livers to determine whether this formation from phosphatidylglycerol was absolutely dependent on cytidinediphosphodiglyceride, as previously reported for intact mitochondria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2397096", "endSection": "abstract" }, { "offsetInBeginSection": 65, "offsetInEndSection": 246, "text": "Cardiolipin (CL) is a key phospholipid in mitochondrial membranes, playing important roles in maintaining the functional integrity and dynamics of mitochondria in animals and yeasts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24443516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Cardiolipin, the specific phospholipid of mitochondria, is involved in the biogenesis, the dynamics, and the supramolecular organization of mitochondrial membranes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23200781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26301254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Since it has been recognized that mitochondria are crucial not only for energy metabolism but also for other cellular functions, there has been a growing interest in cardiolipin, the specific phospholipid of mitochondrial membranes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24769127", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 259, "text": "Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be a determinant in this adaptive mechanism since it modulates the activity of most membrane proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25843549", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 764, "text": "Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3718705", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 530, "text": "Cardiolipin is normally localized to the inner mitochondrial membrane; however, when cardiolipin becomes externalized to the surface of dysregulated mitochondria, it promotes inflammasome activation and stimulates the elimination of damaged or nonfunctional mitochondria by mitophagy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26396268", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 598, "text": "In isolated mitochondrial outer membranes, cardiolipin (diphosphatidylglycerol) increased CPT1 activity 4-fold and the Km for carnitine 6-fold. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21599656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Increasing levels of cardiolipin differentially influence packing of phospholipids found in the mitochondrial inner membrane.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905496", "endSection": "title" }, { "offsetInBeginSection": 261, "offsetInEndSection": 440, "text": "Here, we used Saccharomyces cerevisiae subjected to conditions that affect mitochondrial metabolism as a model to determine the possible role of cardiolipin in stress adaptation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25843549", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 684, "text": "This decline of respiration was attributed to a progressive diminution of the number of mitochondria in copper-treated cells, based on the demonstration of the concomitant decline of (1) cardiolipin (diphosphatidylglycerol) and cytochrome aa3 (cytochrome oxidase), two specific markers of mitochondrial inner membrane, and (2) fumarase activity, a specific marker of mitochondrial matrix space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8977117", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 477, "text": "Diphosphatidylglycerol (DPG) or cardiolipin, a specific component of the inner mitochondrial membrane, represents about 4% of the total lipid content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15460113", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 628, "text": "Experimental results confirmed that the biosynthesis of cardiolipin, from the membrane-bound radioactive phosphatidylglycerol in intact mitochondria isolated from guinea pig and rat liver, was absolutely dependent on CDP-diglycerides and required the addition of divalent cations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2397096", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 776, "text": "We have shown that decrease of cardiolipin in mitochondrial membrane occurs early during ischemia, and only during the irreversible phase of ischemia are phosphatidylethanolamine and phosphatidylcholine broken down.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7378435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Partial purification of diphosphatidylglycerol synthetase from liver mitochondrial membranes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6257342", "endSection": "title" }, { "offsetInBeginSection": 372, "offsetInEndSection": 473, "text": "A small decrease of diphosphatidylglycerol also occurred in the hepatoma mitochondria inner membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7459841", "endSection": "abstract" } ] }, { "body": "Have studies shown that there is no link between DNA methylation patterns and Post Traumatic Stress Disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27886370", "http://www.ncbi.nlm.nih.gov/pubmed/21508515", "http://www.ncbi.nlm.nih.gov/pubmed/25065861", "http://www.ncbi.nlm.nih.gov/pubmed/21714072", "http://www.ncbi.nlm.nih.gov/pubmed/26361058", "http://www.ncbi.nlm.nih.gov/pubmed/22332656", "http://www.ncbi.nlm.nih.gov/pubmed/21306736", "http://www.ncbi.nlm.nih.gov/pubmed/26305478", "http://www.ncbi.nlm.nih.gov/pubmed/26447678", "http://www.ncbi.nlm.nih.gov/pubmed/19793403" ], "ideal_answer": [ "Studies do show a correlation of PTSD-related accelerated aging in DNA methylation patterns." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040921", "http://www.disease-ontology.org/api/metadata/DOID:2055", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013313", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175" ], "type": "yesno", "id": "58e2422c6fddd3e83e000011", "snippets": [ { "offsetInBeginSection": 918, "offsetInEndSection": 1502, "text": "Using pre-deployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC=0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26361058", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1307, "text": " Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26447678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332656", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 321, "text": "In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26361058", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1579, "text": "These results suggest that alterations in global methylation pattern are involved in behavioural adaptation to environmental stress and pinpoint Dlgap2 as a possible target in PTSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793403", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 286, "text": "Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21306736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq.Cases (n = 75) had a postdeployment diagnosis of PTSD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332656", "endSection": "title" }, { "offsetInBeginSection": 146, "offsetInEndSection": 288, "text": "Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21306736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332656", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "AIM: We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22332656", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1398, "text": "Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21714072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793403", "endSection": "title" }, { "offsetInBeginSection": 763, "offsetInEndSection": 885, "text": "Subjects with PTSD showed a higher DNA methylation of four CpG sites at the BDNF promoter compared with those without PTSD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27886370", "endSection": "abstract" }, { "offsetInBeginSection": 1427, "offsetInEndSection": 1606, "text": "Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305478", "endSection": "abstract" } ] }, { "body": "Is POLD3 essential for mouse development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27524497" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1427199", "o": "POLD3" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5131353035340028", "o": "POLD3" } ], "ideal_answer": [ "Yes. The Pold3 gene encodes a subunit of the Pol\u03b4 DNA polymerase complex. Pold3 orthologs are not essential in Saccharomyces cerevisiae or chicken DT40 cells, but the Schizosaccharomyces pombe ortholog is essential. POLD3 also has a specialized role in the repair of broken replication forks, suggesting that POLD3 activity could be particularly relevant for cancer cells enduring high levels of DNA replication stress. In mouse, POLD3 is essential for development and is also required for viability in adult animals.", "yes" ], "exact_answer": "yes", "type": "yesno", "id": "5883b8e6e56acf5176000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 528, "text": "The Pold3 gene encodes a subunit of the Pol\u03b4 DNA polymerase complex. Pold3 orthologs are not essential in Saccharomyces cerevisiae or chicken DT40 cells, but the Schizosaccharomyces pombe ortholog\u00a0is essential. POLD3 also has a specialized role in the repair of broken replication forks, suggesting that POLD3 activity could be particularly relevant for cancer cells enduring high levels of DNA replication stress. We report here that POLD3 is essential for mouse development and is also required for viability in adult animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27524497", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 525, "text": "We report here that POLD3 is essential for mouse development and is also required for viability in adult animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27524497", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 528, "text": "We report here that POLD3 is essential for mouse development and is also required for viability in adult animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27524497", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Romosozumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26768288", "http://www.ncbi.nlm.nih.gov/pubmed/25432357", "http://www.ncbi.nlm.nih.gov/pubmed/26232375", "http://www.ncbi.nlm.nih.gov/pubmed/24272917", "http://www.ncbi.nlm.nih.gov/pubmed/26277199", "http://www.ncbi.nlm.nih.gov/pubmed/27487526", "http://www.ncbi.nlm.nih.gov/pubmed/26557374", "http://www.ncbi.nlm.nih.gov/pubmed/26529924", "http://www.ncbi.nlm.nih.gov/pubmed/26451332", "http://www.ncbi.nlm.nih.gov/pubmed/24433088", "http://www.ncbi.nlm.nih.gov/pubmed/24382002", "http://www.ncbi.nlm.nih.gov/pubmed/24870844", "http://www.ncbi.nlm.nih.gov/pubmed/27510350", "http://www.ncbi.nlm.nih.gov/pubmed/27569204", "http://www.ncbi.nlm.nih.gov/pubmed/26082665", "http://www.ncbi.nlm.nih.gov/pubmed/27641143", "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "http://www.ncbi.nlm.nih.gov/pubmed/26989807", "http://www.ncbi.nlm.nih.gov/pubmed/25799662", "http://www.ncbi.nlm.nih.gov/pubmed/24835636", "http://www.ncbi.nlm.nih.gov/pubmed/24490672", "http://www.ncbi.nlm.nih.gov/pubmed/25669441", "http://www.ncbi.nlm.nih.gov/pubmed/24842796" ], "ideal_answer": [ "Romosozumab is humanized monoclonal antibody to sclerostin. It inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. This dual effect of romosozumab leads to rapid and substantial increases in areal bone mineral density as measured by dual-energy X-ray absorptiometry. It is developed for osteoporosis treatment." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ], "type": "summary", "id": "5880e089c872c9556500000b", "snippets": [ { "offsetInBeginSection": 416, "offsetInEndSection": 681, "text": "The current review will focus on emerging treatments of osteoporosis with the potential of enhanced anabolic effects (romosozumab and abaloparatide) or uncoupling of resorption and formation (odanacatib and romosozumab) as well as the effect of combination therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26989807", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1443, "text": "Newer anabolic agents are imminent and include an analogue of parathyroid hormone-related protein, abaloparatide, and a humanised monoclonal antibody to an inhibitor of bone formation, romosozumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27510350", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1022, "text": " Several humanized monoclonal antibodies to sclerostin, including romosozumab and blosozumab, are now in clinical development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25669441", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 216, "text": "Romosozumab, an antibody raised against sclerostin, is a promising bone anabolic agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Romosozumab inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. This dual effect of romosozumab leads to rapid and substantial increases in areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26232375", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1146, "text": "Phase I and II studies of the two humanized sclerostin monoclonal antibodies, romosozumab and blosozumab, both of which have had positive effects on bone mineral density.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26082665", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1368, "text": "Romosozumab, an anti-sclerosin antibody, and abaloparatide, a PTH-related peptide analog, are at present in advanced stages of clinical evaluation, so far demonstrating efficaciousness together with a favorable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26277199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Romosozumab is a humanized immunoglobulin G2 monoclonal antibody that binds and blocks the action of sclerostin, a protein secreted by the osteocyte and an extracellular inhibitor of canonical Wnt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569204", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 621, "text": "Advances in understanding the mechanisms of action of this signaling molecule have led to the development of a pharmacological inhibitor of sclerostin with potential clinical applications as an osteoanabolic drug for the treatment of osteoporosis.Romosozumab is the first humanized monoclonal sclerostin antibody to be tested in clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Update on romosozumab : a humanized monoclonal antibody to sclerostin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: a randomized, double-blind, placebo-controlled study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24272917", "endSection": "title" }, { "offsetInBeginSection": 539, "offsetInEndSection": 653, "text": "AREAS COVERED: Romosozumab is the first humanized monoclonal sclerostin antibody to be tested in clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 167, "text": "The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24382002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Romosozumab (formerly AMG 785/CDP7851) is a monoclonal antibody that blocks sclerostin from inhibiting osteoblast maturation and function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24272917", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 217, "text": "Romosozumab, an antibody raised against sclerostin, is a promising bone anabolic agent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25799662", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 775, "text": "Phase II clinical trials with anti-sclerostin antibodies, romosozumab and blosozumab, demonstrated a marked increase in bone mineral density after one year of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26529924", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 1022, "text": "Similar to preclinical animal studies with sclerostin antibodies, initial clinical studies show that romosozumab increases bone formation and bone mineral density.EXPERT OPINION: Blocking sclerostin action with romosozumab is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis; efficacy and safety data on large controlled studies are awaited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 651, "text": "Advances in understanding the mechanisms of action of this signaling molecule have led to the development of a pharmacological inhibitor of sclerostin with potential clinical applications as an osteoanabolic drug for the treatment of osteoporosis.AREAS COVERED: Romosozumab is the first humanized monoclonal sclerostin antibody to be tested in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Romosozumab (formerly AMG 785/CDP7851) is a monoclonal antibody that blocks sclerostin from inhibiting osteoblast maturation and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24272917", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 564, "text": "The monoclonal antibody romosozumab binds to sclerostin and increases bone formation.METHODS: In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24382002", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 980, "text": "Blocking sclerostin action with romosozumab is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis; efficacy and safety data on large controlled studies are awaited..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Romosozumab is a humanized immunoglobulin G monoclonal antibody that binds and blocks the action of sclerostin, a protein secreted by the osteocyte and an extracellular inhibitor of canonical Wnt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569204", "endSection": "abstract" } ] }, { "body": "Symptoms of which disorder are evaluated with the Davidson Trauma Scale?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16600574", "http://www.ncbi.nlm.nih.gov/pubmed/15076016", "http://www.ncbi.nlm.nih.gov/pubmed/26502199", "http://www.ncbi.nlm.nih.gov/pubmed/24216181", "http://www.ncbi.nlm.nih.gov/pubmed/9122295", "http://www.ncbi.nlm.nih.gov/pubmed/17224720", "http://www.ncbi.nlm.nih.gov/pubmed/27418378", "http://www.ncbi.nlm.nih.gov/pubmed/11891997", "http://www.ncbi.nlm.nih.gov/pubmed/21034691", "http://www.ncbi.nlm.nih.gov/pubmed/23212598", "http://www.ncbi.nlm.nih.gov/pubmed/25763455", "http://www.ncbi.nlm.nih.gov/pubmed/22209270", "http://www.ncbi.nlm.nih.gov/pubmed/19282141", "http://www.ncbi.nlm.nih.gov/pubmed/18436427", "http://www.ncbi.nlm.nih.gov/pubmed/16324899", "http://www.ncbi.nlm.nih.gov/pubmed/11552771", "http://www.ncbi.nlm.nih.gov/pubmed/23103549", "http://www.ncbi.nlm.nih.gov/pubmed/23706842", "http://www.ncbi.nlm.nih.gov/pubmed/12798257", "http://www.ncbi.nlm.nih.gov/pubmed/19506776", "http://www.ncbi.nlm.nih.gov/pubmed/25007537", "http://www.ncbi.nlm.nih.gov/pubmed/25709077", "http://www.ncbi.nlm.nih.gov/pubmed/18396192", "http://www.ncbi.nlm.nih.gov/pubmed/15915097", "http://www.ncbi.nlm.nih.gov/pubmed/25049338", "http://www.ncbi.nlm.nih.gov/pubmed/11555345", "http://www.ncbi.nlm.nih.gov/pubmed/10954063", "http://www.ncbi.nlm.nih.gov/pubmed/22475888", "http://www.ncbi.nlm.nih.gov/pubmed/16317314", "http://www.ncbi.nlm.nih.gov/pubmed/19016483", "http://www.ncbi.nlm.nih.gov/pubmed/19268914", "http://www.ncbi.nlm.nih.gov/pubmed/27111262" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "Symptoms" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A0788385" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0788385", "o": "SYMPTOMS" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A11838788" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11838788", "o": "Symptoms" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A7164206" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7164206", "o": "Symptoms" } ], "ideal_answer": [ "Davidson Trauma Scale is used for evaluation of post-traumatic stress disorder." ], "exact_answer": [ "post-traumatic stress disorder", "PTSD" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013568" ], "type": "factoid", "id": "58861d413b87a8a738000002", "snippets": [ { "offsetInBeginSection": 539, "offsetInEndSection": 1221, "text": "Besides, to study its scores' evidence of convergent, discriminant, and predictive validity in relation to other resilience questionnaires (Connor Davidson Resilience Scale 10-item version, Situated Subjective Resilience Questionnaire for Adults and Resiliency Questionnaire for Adults) and to variables such as emotions (Modified Differential Emotions Scale), coping (Person-situation Coping Questionnaire for Adults), anxiety and depression (Hospital Anxiety and Depression Scale), posttraumatic growth (Posttraumatic Growth Inventory), perceived stress (Perceived Stress Scale) and posttraumatic stress (Davidson Trauma Scale), correlation and regression analyses were conducted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26502199", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1796, "text": "Using the normalized population mean of 50 on the SF-36 MH domain score as a cut-off, positive predictive values were 16 and 55% for substantial depression; 20 and 68% for substantial anxiety (Depression Anxiety Stress Scales and HADS, respectively); and 40, 44, and 67% for substantial PTSD symptoms (IES-R, IES, and Davidson Trauma Scale, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27111262", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 714, "text": "METHOD: A randomly selected representative sample of inmates in the Puerto Rico correctional system (N = 1,179) was assessed with the Spanish-language Wender Utah Rating Scale (WURS); the Composite International Diagnostic Interview (CIDI) modules for lifetime/current major depression disorder (MDD), generalized anxiety disorder (GAD), and SUD; the Davidson Trauma Scale (DTS; posttraumatic stress disorder [PTSD]); and self-reports of in-site high-risk behaviors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23212598", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 1295, "text": "After correcting for multiple comparisons, no significant effects were observed on any of the outcomes among the NHW sample; however, within the NHB sample, significant gene \u00d7 environment (G \u00d7 E) interactions were observed for lifetime PTSD (P = .0029) and PTSD symptom severity (P = .0009). In each case, the APOE \u03b54 allele had no effect on the outcomes when combat exposure was low; however, when combat exposure was high, an additive effect was observed such that \u03b54 homozygotes exposed to high levels of combat reported the highest rates of PTSD (92%) and the worst symptom severity scores on the Davidson Trauma Scale (M = 79.5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25709077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Early prognostic screening for posttraumatic stress disorder with the Davidson Trauma Scale and the SPAN.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19016483", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "The Davidson Trauma Scale (DTS) was developed as a self-rating for use in diagnosing and measuring symptom severity and treatment outcome in post-traumatic stress disorder (PTSD); 630 subjects were identified by random digit dialing and evaluated for a history of trauma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11891997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "The purpose of this paper is to assess the reliability and validity of the Spanish version of the Davidson trauma scale (DTS-S) and to determine the prevalence and correlates of post-traumatic stress disorder (PTSD) symptoms in a non-clinical random sample of prison inmates.Probabilistic samples of 1,179 inmates from 26 penal institutions in Puerto Rico were selected using a multistage sampling design", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25763455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Remission in post-traumatic stress disorder (PTSD): effects of sertraline as assessed by the Davidson Trauma Scale, Clinical Global Impressions and the Clinician-Administered PTSD scale.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15076016", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "The Davidson Trauma Scale (DTS) was developed as a self-rating for use in diagnosing and measuring symptom severity and treatment outcome in post-traumatic stress disorder (PTSD); 630 subjects were identified by random digit dialing and evaluated for a history of trauma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11891997", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 718, "text": "Symptoms were assessed at sequential time points by the Structured Interview for PTSD (SIP), a clinician interview based assessment, and a self-report scale, the Davidson Trauma Scale (DTS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10954063", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 427, "text": "The present study focused on platelet serotonin (5-HT) concentration and symptoms of comorbid depression in war veterans with or without PTSD.PTSD and depression were evaluated using Clinician Administered PTSD Scale, Davidson Trauma Scale, Montgomery-Asberg Depression Rating Scale and Hamilton Anxiety Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12798257", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 768, "text": "Although rates of trauma and PTSD are higher in those with bipolar disorder than in the general population, little is known about differences across bipolar subtypes.Using the NIMH STEP-BD dataset (N=3158), this study evaluated whether there were baseline differences in the prevalence of PTSD between participants with bipolar disorder I (BDI) and bipolar disorder II (BDII), using the MINI and the Davidson Trauma Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23706842", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 542, "text": "We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms.PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23103549", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1733, "text": "Using the normalized population mean of 50 on the SF-36 MH domain score as a cut-off, positive predictive values were 16 and 55% for substantial depression; 20 and 68% for substantial anxiety (Depression Anxiety Stress Scales and HADS, respectively); and 40, 44, and 67% for substantial PTSD symptoms (IES-R, IES, and Davidson Trauma Scale, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27111262", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 672, "text": "The Davidson Trauma Scale was completed at 1 (n = 145), 6 (n = 106), 12 (n = 94), and 24 (n = 66) months postdischarge to assess symptoms of PTSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21034691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The Davidson Trauma Scale (DTS) is a validated, 17-item, brief global assessment scale for posttraumatic stress disorder (PTSD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18396192", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 423, "text": "Evaluation of PTSD symptoms using the Davidson Trauma Scale (DTS) and General Health Questionnaire (GHQ) in a sample of 56 patients admitted to an emergency room of a general hospital, and assessment of PTSD symptoms in relatives of the patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16600574", "endSection": "abstract" } ] }, { "body": "What is the function of the Mis18 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25569776", "http://www.ncbi.nlm.nih.gov/pubmed/24774534", "http://www.ncbi.nlm.nih.gov/pubmed/22540025", "http://www.ncbi.nlm.nih.gov/pubmed/24789708", "http://www.ncbi.nlm.nih.gov/pubmed/27239045", "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "http://www.ncbi.nlm.nih.gov/pubmed/21911481", "http://www.ncbi.nlm.nih.gov/pubmed/26343758", "http://www.ncbi.nlm.nih.gov/pubmed/27670610", "http://www.ncbi.nlm.nih.gov/pubmed/19217403", "http://www.ncbi.nlm.nih.gov/pubmed/24269809", "http://www.ncbi.nlm.nih.gov/pubmed/25202874", "http://www.ncbi.nlm.nih.gov/pubmed/21768289" ], "ideal_answer": [ "Kinetochores assemble on a specialized chromosomal locus termed the centromere, which is characterized by the replacement of histone H3 in centromeric nucleosomes with the essential histone H3 variant CENP-A (centromere protein A). The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. Further, we demonstrate Mis18\u00ce\u00b1's crucial role for epigenetic regulation of centromeric chromatin by reinforcing centromeric localization of DNMT3A/3B. Mis18\u00ce\u00b1 interacts with DNMT3A/3B, and this interaction is critical for maintaining DNA methylation and hence regulating epigenetic states of centromeric chromatin. Together, our findings uncover the functional mechanism of Mis18\u00ce\u00b1 and its pivotal role in mammalian cell cycle. The Mis18 complex is a critical player in determining when and where centromeres are built.", "Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres Here we report identification of five fission yeast centromere proteins, Mis14-18. Mis14 is recruited to kinetochores independently of CENP-A, and, conversely, CENP-A does not require Mis14 to associate with centromeres. In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway. Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. Mis16 and Mis18 are the most upstream factors in kinetochore assembly as they can associate with kinetochores in all kinetochore mutants except for mis18 and mis16, respectively.", "The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome.", "Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. A fundamental process in centromere establishment is the incorporation of the histone variant CENP-A into centromeric chromatin, which provides a binding platform for the other centromeric proteins. CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP. Thus, CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly. The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. This is a critical step that is essential for proper centromere function and maintaining the integrity of the genome.", "The Mis18 complex is a critical player in determining when and where centromeres are built. The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. Eukaryotic chromosomes segregate by attaching to microtubules of the mitotic spindle through a chromosomal microtubule binding site called the kinetochore. Centromeres are important structural constituents of chromosomes that ensure proper chromosome segregation during mitosis by providing defined sites for kinetochore attachment. Centromeres contain specialized chromatin that includes the centromere-specific histone H3 variant, spCENP-A/Cnp1.", "Together, our findings uncover the functional mechanism of Mis18\u03b1 and its pivotal role in mammalian cell cycle. The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome.", "the mis18 complex has been identified as a critical factor for the centromeric localization of a histone h3 variant, centromeric protein a (cenp-a), which is responsible for the specification of centromere identity in the chromosome." ], "type": "summary", "id": "58af11e67125859353000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "endSection": "title" }, { "offsetInBeginSection": 115, "offsetInEndSection": 335, "text": "Here we report identification of five fission yeast centromere proteins, Mis14-18. Mis14 is recruited to kinetochores independently of CENP-A, and, conversely, CENP-A does not require Mis14 to associate with centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 476, "text": "In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 866, "text": "Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. Mis16 and Mis18 are the most upstream factors in kinetochore assembly as they can associate with kinetochores in all kinetochore mutants except for mis18 and mis16, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 640, "text": "The Mis18 complex, and, in particular, its member M18BP1 was shown to be essential for both incorporation and maintenance of CENP-A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540025", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 599, "text": " CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21911481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Roles of Mis18\u03b1 in epigenetic regulation of centromeric chromatin and CENP-A loading", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 514, "text": "Here, we generated Mis18\u03b1 conditional knockout mice and found that Mis18\u03b1 deficiency resulted in lethality at early embryonic stage with severe defects in chromosome segregation caused by mislocalization of CENP-A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 664, "text": "Further, we demonstrate Mis18\u03b1's crucial role for epigenetic regulation of centromeric chromatin by reinforcing centromeric localization of DNMT3A/3B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 827, "text": "Mis18\u03b1 interacts with DNMT3A/3B, and this interaction is critical for maintaining DNA methylation and hence regulating epigenetic states of centromeric chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1003, "text": "Mis18\u03b1 deficiency led to reduced DNA methylation, altered histone modifications, and uncontrolled noncoding transcripts in centromere region by decreased DNMT3A/3B enrichment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "endSection": "abstract" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1116, "text": "Together, our findings uncover the functional mechanism of Mis18\u03b1 and its pivotal role in mammalian cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Centromere licensing: Mis18 is required to Polo-ver", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25202874", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The Mis18 complex is a critical player in determining when and where centromeres are built", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25202874", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 972, "text": "Its nearest relatives are yippee, a highly conserved eukaryotic protein of unknown function, and Mis18, a protein involved in the priming of centromeres for recruitment of CENP-A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25569776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Mis16 and Mis18 are subunits of a protein complex required for incorporation of the histone H3 variant CenH3 (Cnp1/CENP-A) into centromeric chromatin in Schizosaccharomyces pombe and mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19217403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The Mis18 proteins (Mis18\u03b1, Mis18\u03b2, and M18BP1) are pivotal to the deposition of CENP-A at the centromere during cell cycle progression and are indispensable for embryonic development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27670610", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 471, "text": "Although Mis18\u03b1 and Mis18\u03b2 are highly homologous proteins, we find that their conserved YIPPEE domains mediate distinct interactions that are essential to link new CENP-A deposition to existing centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27239045", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 975, "text": "Its nearest relatives are yippee, a highly conserved eukaryotic protein of unknown function, and Mis18, a protein involved in the priming of centromeres for recruitment of CENP-A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25569776", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 651, "text": "Ectopically targeted CENP-A chromatin at the LacO array was sufficient to direct the assembly of a functional centromere as indicated by the recruitment of the constitutive centromere-associated network proteins, the microtubule-binding protein NDC80, and the formation of stable kinetochore-microtubule attachments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21768289", "endSection": "abstract" }, { "offsetInBeginSection": 64, "offsetInEndSection": 208, "text": "Replication-independent incorporation of CENP-A at centromeres depends on its chaperone HJURP(Scm3), and Mis18 in vertebrates and fission yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789708", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1261, "text": "Our findings suggest that Eic1 serves a function analogous to that of Mis18BP1(KNL2), thus representing the functional counterpart of Mis18BP1(KNL2) in fission yeast that connects with a module within the CCAN/Mis6/Ctf19 complex to allow the temporally regulated recruitment of the Mis18/Scm3(HJURP) Cnp1(CENP-A) loading factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789708", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 215, "text": "Here, we show that Mis18\u00e2, a component of Mis18 complex governing CENP-A localization, is a new substrate of \u00e2TrCP-containing SCF complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24269809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Schizosaccharomyces pombe centromere protein Mis19 links Mis16 and Mis18 to recruit CENP-A through interacting with NMD factors and the SWI/SNF complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24774534", "endSection": "title" }, { "offsetInBeginSection": 108, "offsetInEndSection": 245, "text": "The fission yeast Schizosaccharomyces pombe and mammalian Mis16 and Mis18 form a complex essential for CENP-A recruitment to centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24774534", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1227, "text": "Its nearest relatives are yippee, a highly conserved eukaryotic protein of unknown function, and Mis18, a protein involved in the priming of centromeres for recruitment of CENP-A. Searches for distant homologs point to an evolutionary relationship of CULT, yippee, and Mis18 to proteins sharing a common fold, which consists of two four-stranded \u03b2-meanders packing at a roughly right angle and coordinating a zinc ion at their apex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25569776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Schizosaccharomyces pombe centromere protein Mis19 links Mis16 and Mis18 to recruit CENP-A through interacting with NMD factors and the SWI/SNF complex", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24774534", "endSection": "title" }, { "offsetInBeginSection": 336, "offsetInEndSection": 475, "text": "In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789708", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "endSection": "title" }, { "offsetInBeginSection": 773, "offsetInEndSection": 932, "text": "No Mis18BP1(KNL2) orthologue has been identified in fission yeast, consequently it remains unknown how the key Cnp1(CENP-A) loading factor Mis18 is recruited. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789708", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 477, "text": "In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15369671", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 451, "text": "In fission yeast, Scm3sp and the Mis18 complex, composed of Mis16, Eic1, and Mis18, function as a CENP-A(Cnp1)-specific chaperone and a recruiting factor, respectively, and together ensure accurate delivery of CENP-A(Cnp1) to centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26343758", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1228, "text": "Its nearest relatives are yippee, a highly conserved eukaryotic protein of unknown function, and Mis18, a protein involved in the priming of centromeres for recruitment of CENP-A. Searches for distant homologs point to an evolutionary relationship of CULT, yippee, and Mis18 to proteins sharing a common fold, which consists of two four-stranded \u03b2-meanders packing at a roughly right angle and coordinating a zinc ion at their apex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25569776", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 931, "text": "No Mis18BP1(KNL2) orthologue has been identified in fission yeast, consequently it remains unknown how the key Cnp1(CENP-A) loading factor Mis18 is recruited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789708", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 599, "text": "CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21911481", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 716, "text": "We find that Mis18\u03b1 directly interacts with the N terminus of Mis18BP1, whereas Mis18\u03b2 directly interacts with CENP-C during G1 phase, revealing that these proteins have evolved to serve distinct functions in centromeres of higher eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27239045", "endSection": "abstract" } ] }, { "body": "Are hepadnaviral minichromosomes free of nucleosomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3023620", "http://www.ncbi.nlm.nih.gov/pubmed/8649399", "http://www.ncbi.nlm.nih.gov/pubmed/1337883", "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "http://www.ncbi.nlm.nih.gov/pubmed/8380890", "http://www.ncbi.nlm.nih.gov/pubmed/21331901" ], "ideal_answer": [ "Nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned.", "In vitro assembled minichromosomes were able to replicate efficiently in vitro, when the DNA was preincubated with T-antigen, a cytosolic S100 extract and three deoxynucleoside triphosphates prior to chromatin assembly, indicating that the origin has to be free of nucleosomes for replication initiation. The transcriptionally inactive locus is covered by an array of positioned nucleosomes extending over 1,400 bp. In minichromosomes with a (mu)LCR or DNase I-hypersensitive site 2 (HS2) which actively transcribe the epsilon-globin gene, the nucleosome at the promoter is altered or disrupted while positioning of nucleosomes in the rest of the locus is retained. Viral minichromosomes were found to exist in at least two defined structures covered with 11 or 12 nucleosomes, leaving open gaps accessible for interactions with other host factors. Minichromosomes from both preparations contain the full complement of nucleosomes, but salt treatment removes histone H1 and a fraction of nonhistone chromatin proteins. This double-stranded DNA serves as a template for replication as well as transcription and is assembled into host nucleosomes, yielding circular viral minichromosomes. In contrast, the replicated untreated minichromosomes were found to be densely packed with nucleosomes, indicating that an assembly of new nucleosomes occurred during in vitro replication.", "Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples. In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings.", "nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned. In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings." ], "exact_answer": "no", "type": "yesno", "id": "58e3d1743e8b6dc87c000001", "snippets": [ { "offsetInBeginSection": 556, "offsetInEndSection": 782, "text": "Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1024, "text": "In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1160, "text": "nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 593, "text": "Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "title" }, { "offsetInBeginSection": 212, "offsetInEndSection": 554, "text": "To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 497, "text": "Mature SV40 minichromosomes are estimated to contain about 27 nucleosomes (error +/- 2), except for those molecules with a nucleosome-free gap, which are interpreted to contain 25 nucleosomes (error +/- 2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3023620", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 791, "text": "In vitro replication in the presence of protein-free competitor DNA shows that replicating trypsinized minichromosomes do not lose nucleosomes and replicating competitor DNA does not gain nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8649399", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 795, "text": "In vitro replication in the presence of protein-free competitor DNA shows that replicating trypsinized minichromosomes do not lose nucleosomes and replicating competitor DNA does not gain nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8649399", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 793, "text": "We conclude that in both cases parental nucleosomes are transferred to progeny DNA, and, in addition, that an assembly of new nucleosomes occurs during the replication of native minichromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1337883", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 845, "text": "In contrast, the replicated untreated minichromosomes were found to be densely packed with nucleosomes, indicating that an assembly of new nucleosomes occurred during in vitro replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8380890", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 593, "text": "Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331901", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 554, "text": "To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "title" }, { "offsetInBeginSection": 213, "offsetInEndSection": 555, "text": "To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787202", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 595, "text": "Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331901", "endSection": "abstract" } ] }, { "body": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7896290", "http://www.ncbi.nlm.nih.gov/pubmed/11810654", "http://www.ncbi.nlm.nih.gov/pubmed/24556499", "http://www.ncbi.nlm.nih.gov/pubmed/2988137", "http://www.ncbi.nlm.nih.gov/pubmed/9464278", "http://www.ncbi.nlm.nih.gov/pubmed/995018", "http://www.ncbi.nlm.nih.gov/pubmed/9718678", "http://www.ncbi.nlm.nih.gov/pubmed/7713510", "http://www.ncbi.nlm.nih.gov/pubmed/7757083", "http://www.ncbi.nlm.nih.gov/pubmed/21045963", "http://www.ncbi.nlm.nih.gov/pubmed/1606717", "http://www.ncbi.nlm.nih.gov/pubmed/23450488", "http://www.ncbi.nlm.nih.gov/pubmed/23455788", "http://www.ncbi.nlm.nih.gov/pubmed/9284926", "http://www.ncbi.nlm.nih.gov/pubmed/27144168", "http://www.ncbi.nlm.nih.gov/pubmed/7762563", "http://www.ncbi.nlm.nih.gov/pubmed/16953888" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0008668", "o": "http://linkedlifedata.com/resource/umls/label/A18590602" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18590602", "o": "5 chromosome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0008668", "o": "http://linkedlifedata.com/resource/umls/label/A7569590" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7569590", "o": "Chromosome 5" } ], "ideal_answer": [ "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5", "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5. ", "syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5 . ", "cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5.", "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:12580", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003410" ], "type": "yesno", "id": "58dbba438acda3452900001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144168", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 571, "text": "The typical cri du chat syndrome, due to 5p15.2 deletion, includes severe intellectual disability, facial dysmorphisms, neonatal hypotonia and pre- and post-natal growth retardation, whereas more distal deletions in 5p15.3 lead to cat-like cry and speech delay and produce the clinical picture of the atypical cri du chat syndrome, with minimal or absent intellectual impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24556499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Cri-du-chat is a human contiguous gene deletion syndrome resulting from hemizygous deletions of chromosome 5p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9464278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Cri-du-chat is a chromosomal deletion syndrome characterized by partial deletion of the short arm of chromosome 5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7896290", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 322, "text": "The karyotype showed a terminal deletion of the short arm of chromosome 5 including the critical region 5p15 for cri du chat syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11810654", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 938, "text": "Fewer than 1 in 200 of cri du chat syndrome cases are due to recombination aneusomy arising from a parental inversion of chromosome 5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1606717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Molecular approach to analyzing the human 5p deletion syndrome, cri du chat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2988137", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Cri-du-chat is a human contiguous gene deletion syndrome resulting from hemizygous deletions of chromosome 5p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9464278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The cri du chat syndrome (CdCS) is a chromosomal deletion syndrome associated with a partial deletion of the short (p) arm of chromosome 5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23455788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "The cri-du-chat syndrome is a contiguous gene syndrome that results from a deletion of the short arm of chromosome 5 (5p).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7762563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome 5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9284926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The deletion of the short arm of chromosome 5 is associated with the cri-du-chat syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7713510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16953888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Cri-du-chat is a well described partial aneusomy resulting from deletion of the short arm of chromosome 5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7757083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Cri-du-chat syndrome is caused by haploinsufficiency of the genes on the distal part of the short arm of chromosome 5, and characteristic features include microcephaly, developmental delays, and a distinctive high-pitched mewing cry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21045963", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 578, "text": "The pathological condition of cri du chat syndrome is due to the cytogenetic deletion of band p15.2 of chromosome 5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9718678", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 875, "text": " Karyotype analysis indicated that the patient has carried a terminal deletion in 5p. FISH with Cri du Chat syndrome region probe confirmed that D5S23 and D5S721 loci are deleted. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23450488", "endSection": "abstract" } ] }, { "body": "What are the roles of Smyd3 in zebrafish?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27377701", "http://www.ncbi.nlm.nih.gov/pubmed/21887258", "http://www.ncbi.nlm.nih.gov/pubmed/25997738" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0043457", "o": "Danio rerio" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0043457", "o": "http://linkedlifedata.com/resource/umls/label/A7574572" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7574572", "o": "Zebrafish" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0043457", "o": "http://linkedlifedata.com/resource/umls/label/A0134867" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0134867", "o": "Zebrafish" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0043457", "o": "http://linkedlifedata.com/resource/umls/label/A18687609" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18687609", "o": "zebrafish" } ], "ideal_answer": [ "Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish. Transcripts of smyd3 are expressed in zebrafish embryos at all developmental stages and knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes are associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog." ], "exact_answer": [ [ "The development of cardiac muscle" ], [ "The development of skeletal muscle" ] ], "concepts": [ "http://www.uniprot.org/uniprot/SMYD3_HUMAN", "http://www.uniprot.org/uniprot/SMYD3_MOUSE", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018482", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029961", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011495", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015027" ], "type": "list", "id": "5883a25d7ffa0d4374000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21887258", "endSection": "title" }, { "offsetInBeginSection": 704, "offsetInEndSection": 1237, "text": "We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes were associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog. These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21887258", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 916, "text": "We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21887258", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 717, "text": "We find both smyd3 and setd7 are highly expressed within developing zebrafish heart and knock-down of these genes led to severe defects in cardiac morphogenesis without altering the expressions pattern of heart markers, including cmlc2, vmhc, and amhc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25997738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21887258", "endSection": "title" }, { "offsetInBeginSection": 238, "offsetInEndSection": 378, "text": "SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27377701", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 380, "text": "SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27377701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21887258", "endSection": "title" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1238, "text": "These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21887258", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by ribociclib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26303211", "http://www.ncbi.nlm.nih.gov/pubmed/27729458", "http://www.ncbi.nlm.nih.gov/pubmed/27017286", "http://www.ncbi.nlm.nih.gov/pubmed/25941111", "http://www.ncbi.nlm.nih.gov/pubmed/26642065", "http://www.ncbi.nlm.nih.gov/pubmed/27030077", "http://www.ncbi.nlm.nih.gov/pubmed/26830312", "http://www.ncbi.nlm.nih.gov/pubmed/27496135", "http://www.ncbi.nlm.nih.gov/pubmed/27493615", "http://www.ncbi.nlm.nih.gov/pubmed/25848011", "http://www.ncbi.nlm.nih.gov/pubmed/27717303", "http://www.ncbi.nlm.nih.gov/pubmed/27810861", "http://www.ncbi.nlm.nih.gov/pubmed/27542767", "http://www.ncbi.nlm.nih.gov/pubmed/26053278", "http://www.ncbi.nlm.nih.gov/pubmed/26995305", "http://www.ncbi.nlm.nih.gov/pubmed/27336726", "http://www.ncbi.nlm.nih.gov/pubmed/26390342", "http://www.ncbi.nlm.nih.gov/pubmed/27087139", "http://www.ncbi.nlm.nih.gov/pubmed/25876993", "http://www.ncbi.nlm.nih.gov/pubmed/26896604" ], "ideal_answer": [ "Ribociclib is inhibitor of cyclin D-cyclin-dependent kinase 4/6 (CDK 4/6). It is used for breast cancer treatment." ], "exact_answer": [ "cyclin D-cyclin-dependent kinase 4/6", "CDK4/6" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798" ], "type": "factoid", "id": "5880dba9c872c95565000009", "snippets": [ { "offsetInBeginSection": 411, "offsetInEndSection": 587, "text": "Three CDK 4/6 inhibitors have been investigated for the treatment of HR(+) breast cancer, including palbociclib (PD 0332991), ribociclib (LEE011), and abemaciclib (LY2835219). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26303211", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 761, "text": "The CDK 4/6 inhibitors are a novel class of therapeutics that target the CDK 4/6 kinases that promote transition through the cell cycle. Currently, palbociclib (PD0332991, Pfizer), abemaciclib (LY2835219, Lilly) and ribociclib (LEE011, Novartis) are being investigated in clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26642065", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1405, "text": "SUMMARY: Palbociclib, abemaciclib and ribociclib have demonstrated very promising clinical activity in breast cancer, liposarcoma, mantel cell lymphoma and melanoma. Moreover, CDK4/6 inhibitors have shown promising preclinical activity in glioblastoma, renal and ovarian cancer models that may provide directions for their future clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26642065", "endSection": "abstract" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1512, "text": "Currently, three selective CDK4/6 inhibitors have been approved or are in late-stage development: palbociclib (PD-0332991), ribociclib (LEE011), and abemaciclib (LY2835219).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27017286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "The combination of antiestrogen therapy and ribociclib, an investigational CDK4/6 inhibitor, led to improved outcomes in women with metastatic HR-positive, HER2-negative breast cancer, according to findings presented at a meeting of the European Society for Medical Oncology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "OBJECTIVES: Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). This study assessed the biological activity of ribociclib (LEE011; CDK4/6 inhibitor) plus letrozole compared with single-agent letrozole in the presurgical setting", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27336726", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 559, "text": "Importantly, 2 other CDK4/6 inhibitors, abemaciclib (LY2835219; Lilly) and ribociclib (LEE011; Novartis), are in the late stage of clinical development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493615", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 803, "text": "After noting an inverse correlation with sensitivity to ribociclib (CDK4/6 inhibitor), we studied the combinatorial effect of these two agents using proliferation assays, cell cycle analysis, Ki67 immunostaining, timelapse microscopy and xenograft studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729458", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 635, "text": "Methods In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27717303", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 795, "text": "Three selective CDK4/6 inhibitors, palbociclib (Ibrance; Pfizer), ribociclib (Novartis), and abemaciclib (Lilly), are in various stages of development in a variety of pRb-positive tumor types, including breast cancer, melanoma, liposarcoma, and non-small cell lung cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25941111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493615", "endSection": "title" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1102, "text": "Targeted inhibition of CDK4/6 pathway by small-molecule inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in inhibition of cell-cycle progression, amelioration of kidney injury, and improved overall survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493615", "endSection": "title" } ] }, { "body": "Which histone mutations have been associated with pediatric gliomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27444975", "http://www.ncbi.nlm.nih.gov/pubmed/23429371", "http://www.ncbi.nlm.nih.gov/pubmed/27048880", "http://www.ncbi.nlm.nih.gov/pubmed/27622066", "http://www.ncbi.nlm.nih.gov/pubmed/23715325", "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "http://www.ncbi.nlm.nih.gov/pubmed/23417712", "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "http://www.ncbi.nlm.nih.gov/pubmed/25200322", "http://www.ncbi.nlm.nih.gov/pubmed/24285547", "http://www.ncbi.nlm.nih.gov/pubmed/23539183", "http://www.ncbi.nlm.nih.gov/pubmed/25170156", "http://www.ncbi.nlm.nih.gov/pubmed/25401693", "http://www.ncbi.nlm.nih.gov/pubmed/27135271", "http://www.ncbi.nlm.nih.gov/pubmed/26376656", "http://www.ncbi.nlm.nih.gov/pubmed/25773741" ], "ideal_answer": [ "About 80% of Diffuse intrinsic pontine glioma (DIPG) cases and 70% of midline glioblastomas contain a mutation at one allele of the H3F3A gene (encoding histone H3 variant H3.3), replacing the lysine 27 with methionine (K27M). Moreover, approximately 30% of pediatric high grade gliomas (pedHGG) including GBM and DIPG harbor a lysine 27 mutation (K27M) in histone 3.3 (H3.3) which is correlated with poor outcome. Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1)", "Moreover, approximately 30% of pediatric high grade gliomas (pedHGG) including GBM and DIPG harbor a lysine 27 mutation (K27M) in histone 3.3 (H3.3) which is correlated with poor outcome and was shown to influence EZH2 function Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1) Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases.", "Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1). Two new studies show that the known histone H3 alteration p.Lys27Met in pediatric glioma leads to globally diminished trimethylation at histone H3 lysine 27. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis.", ", approximately 30% of pediatric high grade gliomas (pedhgg) including gbm and dipg harbor a lysine 27 mutation (k27m) in histone 3.3 (h3.3) which is correlated with poor outcome and was shown to influence ezh2 function . the h3f3a mutant allele found in high-grade pediatric glioma by real-time pcr . studies on high-grade pediatric gbm have identified two recurrent mutations (k27m and g34r/v) in genes encoding histone h3 (h3f3a for h3.3 and hist1h3b for h3.1) . has been reported recently that about 80% of dipg cases and 70% of midline glioblastomas contain a mutation at one allele of the h3f3a gene (encoding histone h3 variant h3.3) , replacing the lysine 27 with methionine (k27m). . , discuss vaccine treatment for children diagnosed with malignant glioma , through targeting epha2 , il-13r\u03b12 and/or histone h3 k27m , while in adults , treatments with rintega , prophage series g-100 and dendritic cells are explored. . studies have identified a lys 27-to-methionine (k27m) mutation at one allele of h3f3a , one of the two genes encoding histone h3 variant h3.3 , in 60% of high-grade pediatric glioma cases. . new studies show that the known histone h3 alteration p.lys27met in pediatric glioma leads to globally diminished trimethylation at histone h3 lysine 27 . were able to discern the h3f3a k27m mutation in a newly obtained pediatric brainstem glioblastoma sample whose h3.3 status was not known previously , and in three other dipg samples as well as paraffin embedded samples these results demonstrate that have developed a new reliable procedure for detecting the h3f3a k27m mutation in pediatric glioblastoma patient samples. . " ], "exact_answer": [ [ "K27M in H3F3A" ], [ "G34R/V in HIST1H3B" ] ], "type": "list", "id": "58a6c94860087bc10a00002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Detecting the H3F3A mutant allele found in high-grade pediatric glioma by real-time PCR", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376656", "endSection": "title" }, { "offsetInBeginSection": 128, "offsetInEndSection": 355, "text": " It has been reported recently that about 80% of DIPG cases and 70% of midline glioblastomas contain a mutation at one allele of the H3F3A gene (encoding histone H3 variant H3.3), replacing the lysine 27 with methionine (K27M).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376656", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 481, "text": "In order to facilitate diagnosis of DIPG patients, a quick and reliable method to identify the H3F3A K27M mutation is needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376656", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1240, "text": "Using this optimized real-time PCR assay, we analyzed eleven samples, two of which containing H3F3A K27M mutation, and found that these two samples were differentially amplified from the nine others. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376656", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1629, "text": "we were able to discern the H3F3A K27M mutation in a newly obtained pediatric brainstem glioblastoma sample whose H3.3 status was not known previously, and in three other DIPG samples as well as paraffin embedded samples. These results demonstrate that we have developed a new reliable procedure for detecting the H3F3A K27M mutation in pediatric glioblastoma patient samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376656", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 739, "text": "Moreover, approximately 30% of pediatric high grade gliomas (pedHGG) including GBM and DIPG harbor a lysine 27 mutation (K27M) in histone 3.3 (H3.3) which is correlated with poor outcome and was shown to influence EZH2 function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27135271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "endSection": "title" }, { "offsetInBeginSection": 72, "offsetInEndSection": 240, "text": "Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 620, "text": "Genome-wide studies using ChIP-seq on H3.3K27M patient samples indicate a global reduction of H3K27me3 on chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 788, "text": "Remarkably, we also found a dramatic enrichment of H3K27me3 and EZH2 (the catalytic subunit H3K27 methyltransferase) at hundreds of gene loci in H3.3K27M patient cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Two new studies show that the known histone H3 alteration p.Lys27Met in pediatric glioma leads to globally diminished trimethylation at histone H3 lysine 27. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23715325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 924, "text": "These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 568, "text": "Here, we discuss vaccine treatment for children diagnosed with malignant glioma, through targeting EphA2, IL-13R\u03b12 and/or histone H3 K27M, while in adults, treatments with RINTEGA, Prophage Series G-100 and dendritic cells are explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27622066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25170156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Sequencing of pediatric gliomas has identified missense mutations Lys27Met (K27M) and Gly34Arg/Val (G34R/V) in genes encoding histone H3.3 (H3F3A) and H3.1 (HIST3H1B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 648, "text": "Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78\u00a0% of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36\u00a0% of non-brainstem gliomas carrying either K27M or G34R/V mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "title" }, { "offsetInBeginSection": 146, "offsetInEndSection": 455, "text": "Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "title" }, { "offsetInBeginSection": 400, "offsetInEndSection": 650, "text": "Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78\u00a0% of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36\u00a0% of non-brainstem gliomas carrying either K27M or G34R/V mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 253, "text": "Recent sequencing studies have shown that ~30\u00a0% of pediatric GBM and ~80\u00a0% of diffuse intrinsic pontine gliomas show K27M mutations in the H3F3A gene, a variant encoding histone H3.3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25200322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25170156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Sequencing of pediatric gliomas has identified missense mutations Lys27Met (K27M) and Gly34Arg/Val (G34R/V) in genes encoding histone H3.3 (H3F3A) and H3.1 (HIST3H1B)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23539183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 454, "text": "Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25401693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 386, "text": "We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25170156", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 254, "text": "Recent sequencing studies have shown that ~30\u00a0% of pediatric GBM and ~80\u00a0% of diffuse intrinsic pontine gliomas show K27M mutations in the H3F3A gene, a variant encoding histone H3.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25200322", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 604, "text": "Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048880", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 1070, "text": "Moreover, approximately 30% of pediatric high grade gliomas (pedHGG) including GBM and DIPG harbor a lysine 27 mutation (K27M) in histone 3.3 (H3.3) which is correlated with poor outcome and was shown to influence EZH2 function.The present study investigated the correlation of expression of EZH2 and other PRC2 genes (EZH1, SUZ12, EED) with overall survival of pediatric GBM patients and the cytotoxic impact of EZH2 inhibition by the novel agent Tazemetostat in pediatric GBM/DIPG cells harboring either a H3.3 mutation or a H3 wildtype.EZH2 gene expression does not c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27135271", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 651, "text": "Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78\u00a0% of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36\u00a0% of non-brainstem gliomas carrying either K27M or G34R/V mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1352, "text": "Important insights have also been uncovered in the field of pediatric glioma, including the identification of recurrent mutation, fusion, and/or duplication events of the BRAF, FGFR1, MYB, and MYBL1 genes in pediatric low-grade gliomas, mutations affecting histone components (H3F3A p.K27M or p.G34) in pediatric high-grade gliomas, and aggressive subsets developing in midline central nervous system structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27444975", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1261, "text": "K27M-H3.3 is universally associated with short survival in DIPG, while patients wild-type for H3.3 show improved survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "abstract" }, { "offsetInBeginSection": 1481, "offsetInEndSection": 1704, "text": "Taken together, our results suggest that mutations disrupting the histone code at H3K36, including H3.3 G34R/V, IDH1 and/or SETD2 mutations, are central to the genesis of hemispheric HGGs in older children and young adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23417712", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1284, "text": "Gliomas with H3F3A K27M from pediatric or young adult patients had similar, characteristic DNA methylation profiles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285547", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1263, "text": "K27M-H3.3 is universally associated with short survival in DIPG, while patients wild-type for H3.3 show improved survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 794, "text": "Moreover, the gain of H3K27me3 and Ezh2 at gene promoters alters the expression of genes that are associated with various cancer pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "endSection": "title" } ] }, { "body": "Is it feasible to obtain DNA read lengths that exceed 30 Kb?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27712583", "http://www.ncbi.nlm.nih.gov/pubmed/25977818", "http://www.ncbi.nlm.nih.gov/pubmed/27587671" ], "ideal_answer": [ "The emergence and development of so called third generation sequencing platforms such as PacBio has permitted exceptionally long reads (over 20\u2009kb) to be generated but not yet read length >30 Kb." ], "exact_answer": "no", "type": "yesno", "id": "58dff5776fddd3e83e000008", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 368, "text": "Single-molecule, real-time sequencing (SMRT) developed by Pacific BioSciences produces longer reads than secondary generation sequencing technologies such as Illumina. The long read length enables PacBio sequencing to close gaps in genome assembly, reveal structural variations, and identify gene isoforms with higher accuracy in transcriptomic sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27587671", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 513, "text": " Third-generation sequencing, with read lengths>10 kb, will improve the assembly of complex genomes, but these techniques require high-molecular-weight genomic DNA (gDNA), and gDNA extraction protocols used for obtaining smaller fragments for short-read sequencing are not suitable for this purpose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27712583", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 383, "text": "The emergence and development of so called third generation sequencing platforms such as PacBio has permitted exceptionally long reads (over 20\u2009kb) to be generated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25977818", "endSection": "abstract" } ] }, { "body": "Is osteocrin expressed exclusively in the bone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15923362", "http://www.ncbi.nlm.nih.gov/pubmed/14523025", "http://www.ncbi.nlm.nih.gov/pubmed/27830782", "http://www.ncbi.nlm.nih.gov/pubmed/17951249" ], "ideal_answer": [ "No, Osteocrin (Ostn) has been detected in the bones and the brain." ], "exact_answer": "no", "type": "yesno", "id": "58df73bd38f7f3e93a000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Evolution of Osteocrin as an activity-regulated factor in the primate brain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27830782", "endSection": "title" }, { "offsetInBeginSection": 390, "offsetInEndSection": 601, "text": "Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27830782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Osteocrin (Ostn) is a recently discovered secreted protein produced by cells of the osteoblast lineage that shows a well conserved homology with members of the natriuretic peptide (NP) family. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17951249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Osteocrin (Ostn), a bone-active molecule, has been shown in animals to be highly expressed in cells of the osteoblast lineage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15923362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14523025", "endSection": "title" } ] }, { "body": "What is Achondroplasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20624921", "http://www.ncbi.nlm.nih.gov/pubmed/24365319", "http://www.ncbi.nlm.nih.gov/pubmed/25823796" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0001080", "o": "Achondroplasia" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0001080", "o": "http://linkedlifedata.com/resource/umls/label/A0385394" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0385394", "o": "ACHONDROPLASIA" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/21", "o": "Achondroplasia" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0001080", "o": "http://linkedlifedata.com/resource/umls/label/A0018520" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0018520", "o": "Achondroplasia" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/rxnorm/id/1024318", "o": "http://linkedlifedata.com/resource/rxnorm/label/3105017" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/rxnorm/label/3105017", "o": "Achondroplasia" } ], "ideal_answer": [ "Achondrogenesis type II also known as Achondroplasia is an autosomal-dominant disease leading to severe micromelic dwarfism", "Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism. ", "Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism.", "achondrogenesis type ii is an autosomal-dominant disease leading to severe micromelic dwarfism.", "achondrogenesis type ii is an autosomal-dominant disease to severe micromelic dwarfism. . " ], "exact_answer": [ "An autosomal dominant form of dwarfism" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:4480", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000130" ], "type": "factoid", "id": "58cefcfb8acda34529000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25823796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Physical basis behind achondroplasia, the most common form of human dwarfism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624921", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Achondroplasia is the best described and most common form of the congenital short-limbed dwarfing conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24365319", "endSection": "abstract" } ] }, { "body": "What is the indication for Mirabegron?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23757386", "http://www.ncbi.nlm.nih.gov/pubmed/24127366", "http://www.ncbi.nlm.nih.gov/pubmed/24078498", "http://www.ncbi.nlm.nih.gov/pubmed/24610862", "http://www.ncbi.nlm.nih.gov/pubmed/26908514", "http://www.ncbi.nlm.nih.gov/pubmed/26665779", "http://www.ncbi.nlm.nih.gov/pubmed/27124860", "http://www.ncbi.nlm.nih.gov/pubmed/23063375", "http://www.ncbi.nlm.nih.gov/pubmed/25521658", "http://www.ncbi.nlm.nih.gov/pubmed/23089348", "http://www.ncbi.nlm.nih.gov/pubmed/23850394", "http://www.ncbi.nlm.nih.gov/pubmed/23182126", "http://www.ncbi.nlm.nih.gov/pubmed/26501573", "http://www.ncbi.nlm.nih.gov/pubmed/22981677", "http://www.ncbi.nlm.nih.gov/pubmed/25791612", "http://www.ncbi.nlm.nih.gov/pubmed/26422675", "http://www.ncbi.nlm.nih.gov/pubmed/24602031", "http://www.ncbi.nlm.nih.gov/pubmed/26663687", "http://www.ncbi.nlm.nih.gov/pubmed/26493129", "http://www.ncbi.nlm.nih.gov/pubmed/20878594", "http://www.ncbi.nlm.nih.gov/pubmed/22384458", "http://www.ncbi.nlm.nih.gov/pubmed/24458878" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/chebi/id/CHEBI:65349", "o": "mirabegron" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2983812", "o": "http://linkedlifedata.com/resource/umls/label/A19588156" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A19588156", "o": "mirabegron" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2983812", "o": "http://linkedlifedata.com/resource/umls/label/A20837597" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20837597", "o": "mirabegron" } ], "ideal_answer": [ "Mirabegron, the first \u5c3e3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms.", "mirabegron, the first \u03b23-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (oab) syndrome symptoms.", "Mirabegron, the first \u03b23-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms.", "Mirabegron, the first \ufffd3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms.", "Mirabegron, the first 3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms. " ], "exact_answer": [ "OverActive Bladder syndrome" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053201" ], "type": "factoid", "id": "58f4b2f070f9fc6f0f000012", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 149, "text": "Mirabegron, the first \u03b23-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26422675", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 529, "text": "The clinical indication for mirabegron is overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency and other storage symptoms in both men and women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26665779", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 685, "text": "Mirabegron has been approved in Japan for the indication of urgency, urinary frequency and urge urinary incontinence associated with OAB, and was recently submitted for approval to U.S. and European authorities for the same indication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22384458", "endSection": "abstract" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1603, "text": "Mirabegron was well tolerated.The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 461, "text": "Mirabegron, the selective \u03b23-adrenoceptor agonist, heralds the latest development for the treatment of overactive bladder (OAB).To present the evidence available on the efficacy and tolerability of mirabegron and to discuss this treatments potential in our setting.We reviewed 11 studies conducted with mirabegron in patients with OAB (2 phase II, 9 phase III), all studies were compared to placebo with 6 studies also including tolterodine as an additional arm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23850394", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1386, "text": "More than 50% of patients had previously discontinued anticholinergics medication for OAB, thus allowing us to obtain data on the effectiveness of mirabegron in patients already treated with anticholinergics.Mirabegron is an efficacious drug which presents a statistically significant reduction in the number of incontinence episodes and in urinary frequency as of 4 weeks, with a higher percentage of dry patients and a higher percentage of patients with reduction \u226550% in the number of incontinence episodes than placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23850394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 657, "text": "Mirabegron, a \u03b2(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB).To assess the efficacy and tolerability of mirabegron versus placebo.Multicenter randomised double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients \u2265 18 yr of age with symptoms of OAB for \u2265 3 mo.After a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50mg, mirabegron 100mg, or tolterodine extended release 4 mg orally once daily for 12 wk.Patients completed a micturition diary and quality-of-life (QoL) assessments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Mirabegron is the first \u03b23-adrenoceptor agonist that is clinically effective for overactive bladder.The effects of mirabegron on primary bladder mechanosensitive single-unit afferent activities (SAAs) and bladder microcontractions were evaluated and compared with the effects of oxybutynin.Female Sprague-Dawley rats were anesthetized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981677", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1538, "text": "Mirabegron exhibits a novel mode of action in targeting the \u03b2\u2083-AR for bladder relaxation, and the studies and trials conducted to date suggest mirabegron as a promising new treatment in the management of OAB symptoms, such as increased urinary urgency and frequency, and urgency incontinence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20878594", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 686, "text": "Mirabegron has been approved in Japan for the indication of urgency, urinary frequency and urge urinary incontinence associated with OAB, and was recently submitted for approval to U.S. and European authorities for the same indication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22384458", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 532, "text": "The clinical indication for mirabegron is overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency and other storage symptoms in both men and women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26665779", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 371, "text": "Mirabegron's efficacy on frequency, urgency, and urge incontinence was tested in several trials before its wide clinical introduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26501573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 540, "text": "To discuss the pharmacotherapeutic aspects of Mirabegron which is a first-in class novel \u03b23 receptor agonist drug recently approved by the food and drug administration (FDA) for the treatment of overactive bladder (OAB).We conducted a computerized search of the MEDLINE/PUBMED databases with the word Mirabegron, \u03b23 receptor agonist and overactive bladder.Effect of Mirabegron on \u03b23 adrenergic receptor purportedly releases nitric oxide(NO) by an increase in intracellular Ca2+ through accumulation of cyclic adenosine monophosphate (cAMP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Mirabegron for the treatment of overactive bladder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22384458", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Mirabegron: a Beta-3 agonist for overactive bladder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25521658", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "[MIRABEGRON--A NEW DRUG FOR TREATMENT OF OVERACTIVE BLADDER].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26665779", "endSection": "title" }, { "offsetInBeginSection": 399, "offsetInEndSection": 650, "text": "Phase III clinical trials in patients with overactive bladder (OAB), mirabegron at daily doses of 25, 50, and 100\u2009mg demonstrated significant efficacy in treating the symptoms of OAB, including micturition frequency, urgency incontinence, and urgency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24127366", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 144, "text": "To review the place in therapy of mirabegron, a new oral \u03b23-adrenergic receptor agonist, for the treatment of overactive bladder (OAB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23757386", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 108, "text": "Mirabegron (YM178) is a \u03b2(3)-adrenoceptor agonist for the treatment of overactive bladder (OAB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23063375", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 666, "text": "Two new therapies have emerged for treating overactive bladder (OAB): Mirabegron", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23089348", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 134, "text": " OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26908514", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 188, "text": "irabegron (YM-178), currently in development by Astellas Pharma Inc, is an orally active \u03b2\u2083-adrenoceptor (AR) agonist for the potential symptomatic treatment of overactive bladder (OAB). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20878594", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 166, "text": "To evaluate the efficacy and safety of the \u03b23 -adrenoceptor agonist, mirabegron, compared with placebo in Japanese patients with overactive bladder (OAB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26663687", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 284, "text": "Mirabegron is the first \u03b23 -adrenoceptor agonist approved for treatment of overactive bladder syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493129", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 162, "text": "To examine the effects of mirabegron, a selective \u03b23 -adrenoceptor agonist that has recently been approved for the treatment of overactive bladder (OAB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27124860", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 122, "text": "mirabegron is a \u03b23-adrenoceptor agonist developed for the treatment of symptoms of overactive bladder (OAB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24610862", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 191, "text": "mirabegron, a \u03b23-adrenoceptor agonist for the treatment of overactive bladder,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25791612", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 237, "text": "critically analyse available phase II and III randomised control trials (RCTs) reporting clinical data about the efficacy and tolerability of Mirabegron (a \u03b2\u2083-adrenoceptor agonist) in the treatment of overactive bladder (OAB) syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24602031", "endSection": "abstract" } ] }, { "body": "What is the cause of Tardive dyskinesia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26979525", "http://www.ncbi.nlm.nih.gov/pubmed/20818603", "http://www.ncbi.nlm.nih.gov/pubmed/24747871", "http://www.ncbi.nlm.nih.gov/pubmed/23157631", "http://www.ncbi.nlm.nih.gov/pubmed/24310603" ], "ideal_answer": [ "Tardive dyskinesia (TD) is a movement disorder characterized by abnormal involuntary facial movements induced by chronic therapy with classical antipsychotic medications." ], "exact_answer": [ "Tardive dyskinesia (TD) is a movement disorder characterized by abnormal involuntary facial movements induced by chronic therapy with classical antipsychotic medications." ], "type": "factoid", "id": "58efa36d70f9fc6f0f000004", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 89, "text": ": Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26979525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Tardive dyskinesia (TD) is a serious, often disabling, movement disorder that is caused by medications that block dopamine receptors (i.e., neuroleptics, anti-emetics). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24310603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Antipsychotics may cause tardive dyskinesia in humans and orofacial dyskinesia in rodents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24747871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Tardive dyskinesia (TD) is a movement disorder characterized by abnormal involuntary facial movements induced by chronic therapy with classical antipsychotic medications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23157631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The objective of this report is to draw attention to tardive dyskinesia (TD) caused by aripiprazole, a third generation antipsychotic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20818603", "endSection": "abstract" } ] }, { "body": "Are alterations in ultraconserved elements associated with colorectal adenocarcinoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22318908", "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "http://www.ncbi.nlm.nih.gov/pubmed/22673945" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1319315", "o": "Colorectal Adenocarcinoma" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1319315", "o": "http://linkedlifedata.com/resource/umls/label/A18681147" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18681147", "o": "colorectal adenocarcinoma" } ], "ideal_answer": [ "yes", "Yes. SNPs within ultraconserved elements (UCEs) may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5-fluorouracil-based chemotherapy." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050861", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050436", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015179" ], "type": "yesno", "id": "587e1e57fc7e8dd84f000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Genetic variants within ultraconserved elements and susceptibility to right- and left-sided colorectal adenocarcinoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318908", "endSection": "title" }, { "offsetInBeginSection": 1481, "offsetInEndSection": 1684, "text": "Our results strongly suggest that several genetic variants in the UCEs may contribute to CRC susceptibility, individually and jointly, and that different genetic etiology may be involved in RCRC and LCRC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673945", "endSection": "title" }, { "offsetInBeginSection": 1786, "offsetInEndSection": 2099, "text": "To the authors' knowledge, this is the first study to evaluate the association between SNPs within UCEs and clinical outcome in patients with CRC. The results suggested that SNPs within UCEs may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5-fluorouracil-based chemotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673945", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Genetic variants within ultraconserved elements and susceptibility to right- and left-sided colorectal adenocarcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318908", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "We investigated whether single nucleotide polymorphisms within ultraconserved elements (UCEs) are associated with susceptibility to overall colorectal cancer (CRC) and susceptibility to tumor site-specific CRC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "We investigated whether single nucleotide polymorphisms within ultraconserved elements (UCEs) are associated with susceptibility to overall colorectal cancer (CRC) and susceptibility to tumor site-specific CRC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673945", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Genetic variants within ultraconserved elements and susceptibility to right- and left-sided colorectal adenocarcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22318908", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "endSection": "title" } ] }, { "body": "What is PANTHER-PSEP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27193693" ], "ideal_answer": [ "PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. Several previous variant pathogenicity prediction methods have been proposed that quantify evolutionary conservation among homologous proteins from different organisms. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors. ", "PANTHER-PSEP is a software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors.", "PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease." ], "type": "summary", "id": "58965c5578275d0c4a00000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27193693", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 673, "text": "PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. Several previous variant pathogenicity prediction methods have been proposed that quantify evolutionary conservation among homologous proteins from different organisms. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27193693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27193693", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 658, "text": "PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27193693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27193693", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 660, "text": "PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27193693", "endSection": "abstract" } ] }, { "body": "What is MPE-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26080409" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0004793", "o": "nucleic acid sequencing" } ], "ideal_answer": [ "MPE-seq (methidiumpropyl-EDTA sequencing) is a new method for the genome-wide characterization of chromatin that involves the digestion of nuclei with MPE-Fe(II) followed by massively parallel sequencing. Like micrococcal nuclease (MNase), MPE-Fe(II) preferentially cleaves the linker DNA between nucleosomes. However, there are differences in the cleavage of nuclear chromatin by MPE-Fe(II) relative to MNase. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias. In particular, the combined use of MPE-seq and MNase-seq enables the identification of noncanonical chromatin structures that are likely to be important for the regulation of gene expression." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020411" ], "type": "summary", "id": "58946d6e7d9090f353000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "MPE-seq, a new method for the genome-wide analysis of chromatin structure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1021, "text": "The analysis of chromatin structure is essential for the understanding of transcriptional regulation in eukaryotes. Here we describe methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. Like micrococcal nuclease (MNase), MPE-Fe(II) preferentially cleaves the linker DNA between nucleosomes. However, there are differences in the cleavage of nuclear chromatin by MPE-Fe(II) relative to MNase. Most notably, immediately upstream of the transcription start site of active promoters, we frequently observed nucleosome-sized (141-190 bp) and subnucleosome-sized (such as 101-140 bp) peaks of digested chromatin fragments with MPE-seq but not with MNase-seq. These peaks also correlate with the presence of core histones and could thus be due, at least in part, to noncanonical chromatin structures such as labile nucleosome-like particles that have been observed in other contexts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1792, "text": "These findings collectively indicate that MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias. In particular, the combined use of MPE-seq and MNase-seq enables the identification of noncanonical chromatin structures that are likely to be important for the regulation of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1590, "text": "These findings collectively indicate that MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1781, "text": "In particular, the combined use of MPE-seq and MNase-seq enables the identification of noncanonical chromatin structures that are likely to be important for the regulation of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 329, "text": "Here we describe methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 1601, "offsetInEndSection": 1792, "text": "In particular, the combined use of MPE-seq and MNase-seq enables the identification of noncanonical chromatin structures that are likely to be important for the regulation of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "MPE-seq, a new method for the genome-wide analysis of chromatin structure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "title" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1600, "text": "These findings collectively indicate that MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 330, "text": "Here we describe methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of Bezlotoxumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "http://www.ncbi.nlm.nih.gov/pubmed/27753689", "http://www.ncbi.nlm.nih.gov/pubmed/25385797", "http://www.ncbi.nlm.nih.gov/pubmed/25486992", "http://www.ncbi.nlm.nih.gov/pubmed/27757389", "http://www.ncbi.nlm.nih.gov/pubmed/27527088", "http://www.ncbi.nlm.nih.gov/pubmed/25451052", "http://www.ncbi.nlm.nih.gov/pubmed/24821719" ], "ideal_answer": [ "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B (TcdB). It is used for prevention of recurrent C. difficile infections." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ], "type": "summary", "id": "588fa24fed9bbee70d000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B developed by Merck&Co. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 320, "text": "Circulating neutralizing antitoxin antibodies are protective in C. difficile infection (CDI), as demonstrated, in part, by the protective effects of actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25385797", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 295, "text": "Actoxumab and bezlotoxumab are human monoclonal antibodies that neutralize the cytotoxic/cytopathic effects of TcdA and TcdB, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451052", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1542, "text": "We compared the bezlotoxumab epitopes in the TcdB receptor binding domain across known TcdB sequences and found that key substitutions within the bezlotoxumab epitopes correlated with the relative differences in potencies of bezlotoxumab against TcdB of some strains, including ribotypes 027 and 078.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Mechanism of action and epitopes of Clostridium difficile toxin B-neutralizing antibody bezlotoxumab revealed by X-ray crystallography.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821719", "endSection": "title" }, { "offsetInBeginSection": 245, "offsetInEndSection": 578, "text": "A combination of the anti-TcdA antibody actoxumab and the anti-TcdB antibody bezlotoxumab is currently under development for the prevention of recurrent C. difficile infections. We demonstrate here through various biophysical approaches that bezlotoxumab binds to specific regions within the N-terminal half of the TcdB CROP domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821719", "endSection": "abstract" }, { "offsetInBeginSection": 999, "offsetInEndSection": 1411, "text": "We also show that bezlotoxumab neutralizes TcdB by blocking binding of TcdB to mammalian cells. Overall, our data are consistent with a model wherein a single molecule of bezlotoxumab neutralizes TcdB by binding via its two Fab regions to two epitopes within the N-terminal half of the TcdB CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821719", "endSection": "abstract" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1535, "text": "We compared the bezlotoxumab epitopes in the TcdB receptor binding domain across known TcdB sequences and found that key substitutions within the bezlotoxumab epitopes correlated with the relative differences in potencies of bezlotoxumab against TcdB of some strains, including ribotypes 027 and 078.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451052", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1089, "text": "We also show that bezlotoxumab neutralizes TcdB by blocking binding of TcdB to mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B developed by Merck & Co.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 293, "text": "Actoxumab and bezlotoxumab are human monoclonal antibodies that neutralize the cytotoxic/cytopathic effects of TcdA and TcdB, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451052", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 674, "text": "The monoclonal antitoxin antibodies actoxumab (anti-TcdA) and bezlotoxumab (anti-TcdB) are currently in development for the prevention of recurrent CDI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27527088", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 708, "text": "A combination of human monoclonal antibodies, actoxumab and bezlotoxumab, directed against TcdA and TcdB, respectively, has been shown to decrease the rate of recurrence in patients treated with standard-of-care antibiotics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25486992", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 319, "text": "Circulating neutralizing antitoxin antibodies are protective in C. difficile infection (CDI), as demonstrated, in part, by the protective effects of actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25385797", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 577, "text": "We demonstrate here through various biophysical approaches that bezlotoxumab binds to specific regions within the N-terminal half of the TcdB CROP domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821719", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 721, "text": "Based on this information, we solved the x-ray structure of the N-terminal half of the TcdB CROP domain bound to Fab fragments of bezlotoxumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821719", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 998, "text": "The structure reveals that the TcdB CROP domain adopts a \u03b2-solenoid fold consisting of long and short repeats and that bezlotoxumab binds to two homologous sites within the CROP domain, partially occluding two of the four putative carbohydrate binding pockets located in TcdB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24821719", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1512, "text": "Overall, our data are consistent with a model wherein a single molecule of bezlotoxumab neutralizes TcdB by binding via its two Fab regions to two epitopes within the N-terminal half of the TcdB CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells. \u00a9 2014 by The American Society for Biochemistry and Molecular Biology, Inc.Copyright \u00a9 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.\u00a9 2012 The Authors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030767", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 934, "text": "In addition, GlaxoSmithKline plc is developing 256066, an inhaled formulation of a PDE4 inhibitor that has demonstrated efficacy in trials in asthma, and apremilast from Celgene Corp has been reported to be effective for the treatment of psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20419594", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1518, "text": "Although further longer-term and comparative efficacy and tolerability data would be beneficial, the current clinical data indicate that apremilast is an effective and well tolerated option for the management of psoriasis and PsA in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26220911", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1665, "text": "No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period.Data were limited to 52 weeks and may not generalize to nonplaque psoriasis.Apremilast was effective in moderate to severe plaque psoriasis.Copyright \u00a9 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.G, p.F1397V) in the lysosomal trafficking regulator (LYST) gene, which is described as the causative gene for Ch\u00e9diak-Higashi syndrome (CHS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24521565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "A frameshift mutation in the LYST gene is responsible for the Aleutian color and the associated Ch\u00e9diak-Higashi syndrome in American mink.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22762706", "endSection": "title" }, { "offsetInBeginSection": 363, "offsetInEndSection": 494, "text": "As with forms of CHS in other species, we report that the mink CHS is linked to the lysosomal trafficking regulator ( LYST ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22762706", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1295, "text": "LYST analysis was performed for 10 patients; seven different mutations were detected in seven patients, whereas no mutation was identified in three patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23804531", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 172, "text": "Ch\u00e9diak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by immunodeficiency, neurological dysfunction, and oculocutaneous albinism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23804531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Mutations in LYST, a gene encoding a putative lysosomal trafficking protein, cause Ch\u00e9diak-Higashi syndrome (CHS), an autosomal recessive disorder typically characterized by infantile-onset hemophagocytic syndrome and immunodeficiency, and oculocutaneous albinism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23521865", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 737, "text": "This phenotype is similar to that reported previously in lvsB mutant cells where the ortholog of the LYST gene, involved in CHS, is mutated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18194410", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 1305, "text": "Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the \u03b2-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25582874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "LYST is a large cytosolic protein that influences the biogenesis of lysosome-related organelles, and mutation of the encoding gene, LYST, can cause Chediak-Higashi syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20617205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Chediak-Higashi syndrome (CHS) is an autosomal recessive hereditary disorder in Japanese Black cattle, caused by a mutation of the Lyst gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23615171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Chediak-Higashi syndrome (CHS) is caused by mutations in the gene encoding LYST protein, the function of which remains poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25425525", "endSection": "abstract" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1586, "text": "Mutations of genes other than LYST were suspected in some cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23804531", "endSection": "abstract" } ] }, { "body": "The pathogen Fusarium graminearum affects what type of plant species?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18179606", "http://www.ncbi.nlm.nih.gov/pubmed/26693688", "http://www.ncbi.nlm.nih.gov/pubmed/26585460", "http://www.ncbi.nlm.nih.gov/pubmed/22516221", "http://www.ncbi.nlm.nih.gov/pubmed/26607286", "http://www.ncbi.nlm.nih.gov/pubmed/26305050", "http://www.ncbi.nlm.nih.gov/pubmed/17031651", "http://www.ncbi.nlm.nih.gov/pubmed/22028654", "http://www.ncbi.nlm.nih.gov/pubmed/21639892", "http://www.ncbi.nlm.nih.gov/pubmed/24779355", "http://www.ncbi.nlm.nih.gov/pubmed/12492838", "http://www.ncbi.nlm.nih.gov/pubmed/17222149", "http://www.ncbi.nlm.nih.gov/pubmed/26198851", "http://www.ncbi.nlm.nih.gov/pubmed/26882849", "http://www.ncbi.nlm.nih.gov/pubmed/26679010", "http://www.ncbi.nlm.nih.gov/pubmed/17555271" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0032098", "o": "http://linkedlifedata.com/resource/umls/label/A18593376" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18593376", "o": "plants" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0032098", "o": "plant" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0032098", "o": "http://linkedlifedata.com/resource/umls/label/A0486695" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0486695", "o": "plant" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0450254", "o": "Pathogenic organism" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0450254", "o": "http://linkedlifedata.com/resource/umls/label/A18639324" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18639324", "o": "pathogenic organism" } ], "ideal_answer": [ "Fusarium graminearum is a broad host pathogen threatening cereal crops in temperate regions around the world.", "Fusarium graminearum is a broad host pathogen threatening cereal crops in temperate regions around the world. " ], "exact_answer": [ "cereal crops" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005670", "http://www.biosemantics.org/jochem#4053737", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010945" ], "type": "factoid", "id": "58f3ca5c70f9fc6f0f00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Fusarium graminearum is a broad host pathogen threatening cereal crops in temperate regions around the world. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26693688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Fusarium head blight (FHB) of small cereals is a disease of global importance with regard to economic losses and mycotoxin contamination harmful to human and animal health. In Germany, FHB is predominantly associated with wheat and F. graminearum is recognised as the major causal agent of the disease, but little is known about FHB of barley", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Fusarium graminearum is a filamentous fungal pathogen that causes wheat Fusarium head blight", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26607286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Disruption of the GABA shunt affects mitochondrial respiration and virulence in the cereal pathogen Fusarium graminearum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305050", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Fusarium graminearum is a ubiquitous pathogen of cereal crops, including wheat, barley, and maize", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17555271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Disruption of the GABA shunt affects mitochondrial respiration and virulence in the cereal pathogen Fusarium graminearum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305050", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The Ascomycete pathogen Fusarium graminearum can infect all cereal species and lower grain yield, quality and safety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18179606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Arabidopsis is susceptible to the cereal ear blight fungal pathogens Fusarium graminearum and Fusarium culmorum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12492838", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Fusarium head blight (FHB) is a devastating disease of small grain cereal crops caused by the necrotrophic pathogen Fusarium graminearum and Fusarium culmorum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17031651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The cereal pathogen Fusarium graminearum threatens food and feed production worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305050", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 165, "text": " necrotrophic fungal pathogen Fusarium that cause head blight and crown rot of cereals including wheat also infect a number of alternative host plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17222149", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 101, "text": "Fusarium species cause Fusarium head blight (FHB) and other important diseases of cereals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21639892", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 131, "text": "usarium graminearum is a toxigenic fungal pathogen that causes Fusarium head blight (FHB) and crown rot on cereal crops worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779355", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 95, "text": "usarium graminearum is the fungal pathogen that causes globally important diseases of cereals ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26882849", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 344, "text": "Fusarium graminearum, the causal agent of head scab disease of small grain cereals which threatens global food security. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26198851", "endSection": "abstract" } ] }, { "body": "List viral vectors used in gene therapy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26611583", "http://www.ncbi.nlm.nih.gov/pubmed/25636961", "http://www.ncbi.nlm.nih.gov/pubmed/26611600", "http://www.ncbi.nlm.nih.gov/pubmed/24519667", "http://www.ncbi.nlm.nih.gov/pubmed/25962909", "http://www.ncbi.nlm.nih.gov/pubmed/26607476" ], "ideal_answer": [ "adeno-associated viruses\nlentiviruses\nherpes simplex viral vector" ], "exact_answer": [ [ "adeno-associated viruses" ], [ "lentiviruses" ], [ "herpes simplex viral vector" ] ], "type": "list", "id": "58ea59273e8b6dc87c000012", "snippets": [ { "offsetInBeginSection": 228, "offsetInEndSection": 450, "text": "Not only can some genetically engineered adenoviral vectors achieve remarkably efficient and specific gene delivery to target cells, but they also may act as anticancer agents by selectively replicating within cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26611583", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 503, "text": ". Using these criteria, we then evaluate approaches made to model PD using viral vectors to date, including both adeno-associated viruses and lentiviruses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26611600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Recombinant AAV (rAAV) vectors are a suitable vector for gene therapy studies because of desired characteristics such as low immunogenicity, transfection of non-dividing and dividing cells, and long-term expression of the transgene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26607476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "Over the last five years, the number of clinical trials involving AAV (adeno-associated virus) and lentiviral vectors continue to increase by about 150 trials each year. For continued success, AAV and lentiviral expression cassettes need to be designed to meet each disease's specific needs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636961", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 633, "text": "describes commonly used gene therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector (AAV))", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25962909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "This study examined the efficacy of gene therapy of lung adenocarcinoma using specifically controlled type I herpes simplex virus recombinant vector expressing Gibbon ape leukemia virus membrane fusion glycoprotein gene (GALV.fus)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24519667", "endSection": "abstract" } ] }, { "body": "Is dexamethasone recommended for treatment of intracerebral hemorrhage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3574383", "http://www.ncbi.nlm.nih.gov/pubmed/16034939", "http://www.ncbi.nlm.nih.gov/pubmed/19108704" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0011777", "o": "dexamethasone" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0011777", "o": "http://linkedlifedata.com/resource/umls/label/A0477612" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0477612", "o": "dexamethasone" } ], "ideal_answer": [ "No. Dexamethasone and other glucocorticoids should be avoided for treatment of intracerebral hemorrhage because they do not improve patient outcome and are associated with increased risk of side effects." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002543", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045506", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4271528", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020299", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003907", "http://www.biosemantics.org/jochem#4271528" ], "type": "yesno", "id": "58ec5ffaeda5a5767200000a", "snippets": [ { "offsetInBeginSection": 625, "offsetInEndSection": 684, "text": "Dexamethasone and other glucocorticoids should be avoided. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108704", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 1206, "text": "During the third interim analysis, the death rate at the 21st day was identical in the two groups (dexamethasone vs. placebo, 21 of 46 vs. 21 of 47; chi-square = 0.01, P = 0.93). In contrast, the rate of complications (mostly infections and complications of diabetes) was much higher in the dexamethasone group (chi-square = 10.89, P less than 0.001), leading to early termination of the study. In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3574383", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1206, "text": "In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3574383", "endSection": "abstract" } ] }, { "body": "What happens upon disruption of a TAD boundary?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22495304", "http://www.ncbi.nlm.nih.gov/pubmed/25959774" ], "ideal_answer": [ "rewiring occurred only if the variant disrupted a ctcf-associated boundary domain . of a tad boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. . of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions . ", "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. ", "This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus.", "both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding dna, and a cluster of limb enhancers normally associated with epha4 is misplaced relative to tad boundaries and drives ectopic limb expression of another gene in the locus.", "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. ", "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. ", "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation.", "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. In this way, disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain.", "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. " ], "type": "summary", "id": "58eb984aeda5a57672000008", "snippets": [ { "offsetInBeginSection": 999, "offsetInEndSection": 1109, "text": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959774", "endSection": "title" }, { "offsetInBeginSection": 471, "offsetInEndSection": 798, "text": "Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959774", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 887, "text": "This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959774", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1103, "text": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495304", "endSection": "abstract" } ] }, { "body": "List the classical symptoms of the Moschcowitz syndrome (Thrombotic thrombocytopenic purpura).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3752426", "http://www.ncbi.nlm.nih.gov/pubmed/6757857", "http://www.ncbi.nlm.nih.gov/pubmed/16388418", "http://www.ncbi.nlm.nih.gov/pubmed/6752882", "http://www.ncbi.nlm.nih.gov/pubmed/21853406", "http://www.ncbi.nlm.nih.gov/pubmed/21184040", "http://www.ncbi.nlm.nih.gov/pubmed/14727263", "http://www.ncbi.nlm.nih.gov/pubmed/10668344", "http://www.ncbi.nlm.nih.gov/pubmed/2107174", "http://www.ncbi.nlm.nih.gov/pubmed/9036362", "http://www.ncbi.nlm.nih.gov/pubmed/16240903", "http://www.ncbi.nlm.nih.gov/pubmed/7712934", "http://www.ncbi.nlm.nih.gov/pubmed/10714127", "http://www.ncbi.nlm.nih.gov/pubmed/7863389", "http://www.ncbi.nlm.nih.gov/pubmed/25168331", "http://www.ncbi.nlm.nih.gov/pubmed/11450586", "http://www.ncbi.nlm.nih.gov/pubmed/12923683" ], "ideal_answer": [ "The typical manifestations of Moschocowitz syndrome (Thrombotic-thrombocytopenic purpura) are:\n1) thrombocytopenia, \n2) haemolysis, \n3) fever, \n4) coma and \n5) renal failure." ], "exact_answer": [ [ "thrombocytopenia", "thrombotic microangiopathy" ], [ "haemolysis", "hemolytic anemia" ], [ "fever" ], [ "coma", "neurological symptoms" ], [ "renal failure" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011696", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011697", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.disease-ontology.org/api/metadata/DOID:10772" ], "type": "list", "id": "58dd07488acda34529000025", "snippets": [ { "offsetInBeginSection": 1439, "offsetInEndSection": 1602, "text": "The combination of neurological symptoms, thrombocytopenia, fever, renal failure and hemolytic anemia in a patient taking ticlopidine points to a diagnosis of TTP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10668344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "In addition to the typical manifestations of thrombotic-thrombocytopenic purpura like thrombocytopenia, haemolysis, fever, coma and renal failure, signs of a beginning DIC could be seen in a patient after abdominal surgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3752426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Moschcowitz syndrome or thrombotic thrombocytopenic purpura is a rare disorder with a poor prognosis. This syndrome is characterized by a microangiopathic hemolytic anemia with thrombocytopenia, neurologic symptoms and renal disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6752882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Moschcowitz's syndrome is a rare condition with poor prognosis. It is characterized by a microangiopathic haemolytic anaemia associated with thrombocytopenia, neurological symptoms and renal involvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6757857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Thrombotic thrombocytopenic purpura (TTP), in 1924 first described by Moschcowitz, is a clinically heterogeneous syndrome associated with thrombocytopenia, Coombs-negative hemolytic anemia, neurologic changes, renal impairment, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11450586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Thrombotic thrombocytopenic purpura (TTP), in 1924 first described by Moschcowitz, is a clinically heterogeneous syndrome associated with thrombocytopenia, Coombs-negative hemolytic anemia, neurologic changes, renal impairment, and fever", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11450586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Thrombotic thrombocytopenic purpura (TTP, Moschcowitz disease) is characterized by thrombotic microangiopathy leading to microvascular occlusion and ischemic dysfunction of various organs including the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25168331", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "Severe deficiency of von Willebrand factor-cleaving protease (ADAMTS-13) activity (<5% of normal) is specific for classical thrombotic thrombocytopenic purpura (TTP), a disorder presenting with thrombocytopenia, microangiopathic haemolytic anaemia and often with organ dysfunction such as neurological symptoms, renal failure, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12923683", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 370, "text": "In a 57-year-old female patient, who was admitted with fluctuating central neurological abnormalities and generalized purpura, was made the diagnosis of a thrombotic thrombocytopenic purpura (TTP, Moschcowitz' syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10714127", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 862, "text": "Thrombotic thrombocytopenic purpura (TTP) is a syndrome that occurs mainly in adults with multiorgan microvascular thrombosis consisting of thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, renal involvement, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2107174", "endSection": "abstract" } ] }, { "body": "Is airplane stroke syndrome a common disease.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16128878", "http://www.ncbi.nlm.nih.gov/pubmed/26892280", "http://www.ncbi.nlm.nih.gov/pubmed/11914416", "http://www.ncbi.nlm.nih.gov/pubmed/26898578" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0038454", "o": "Stroke" } ], "ideal_answer": [ "No. Only 37 cases of stroke during or soon after long-haul flights have been published. A single center study reported that 42 out of 5727 stroke admissions (0.73%) were flight-related strokes." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020521" ], "type": "yesno", "id": "58ec613ceda5a5767200000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26898578", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 730, "text": "Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26898578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The authors report three cases of ischemic stroke in young adults that occurred during or after an airplane flight.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11914416", "endSection": "abstract" } ] }, { "body": "Which R / bioconductor package is used for enrichment analysis of genomic regions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26508757" ], "ideal_answer": [ "locus overlap analysis (lola) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data.", "Genomic datasets are often interpreted in the context of large-scale reference databases. Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data.", "Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data." ], "exact_answer": [ "LOLA" ], "type": "factoid", "id": "587e3e302420191125000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "LOLA: enrichment analysis for genomic region sets and regulatory elements in R and Bioconductor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508757", "endSection": "title" }, { "offsetInBeginSection": 281, "offsetInEndSection": 467, "text": "Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508757", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 654, "text": "Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data.R package available in Bioconductor and on the following website: http://lola.computational-epigenetics.org.nsheffield@cemm.oeaw.ac.at or cbock@cemm.oeaw.ac.at.\u00a9 The Author 2015", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "LOLA: enrichment analysis for genomic region sets and regulatory elements in R and Bioconductor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508757", "endSection": "title" }, { "offsetInBeginSection": 269, "offsetInEndSection": 655, "text": "Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data.R package available in Bioconductor and on the following website: http://lola.computational-epigenetics.org.nsheffield@cemm.oeaw.ac.at or cbock@cemm.oeaw.ac.at.\u00a9 The Author 2015.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "LOLA: enrichment analysis for genomic region sets and regulatory elements in R and Bioconductor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508757", "endSection": "title" }, { "offsetInBeginSection": 269, "offsetInEndSection": 455, "text": "Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508757", "endSection": "abstract" } ] }, { "body": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21761288", "http://www.ncbi.nlm.nih.gov/pubmed/25921068", "http://www.ncbi.nlm.nih.gov/pubmed/22531175", "http://www.ncbi.nlm.nih.gov/pubmed/19941656", "http://www.ncbi.nlm.nih.gov/pubmed/26656153", "http://www.ncbi.nlm.nih.gov/pubmed/25555396", "http://www.ncbi.nlm.nih.gov/pubmed/17018572", "http://www.ncbi.nlm.nih.gov/pubmed/24137011", "http://www.ncbi.nlm.nih.gov/pubmed/20886259", "http://www.ncbi.nlm.nih.gov/pubmed/17662845", "http://www.ncbi.nlm.nih.gov/pubmed/11973307", "http://www.ncbi.nlm.nih.gov/pubmed/10629039", "http://www.ncbi.nlm.nih.gov/pubmed/22658416" ], "ideal_answer": [ "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. TIRs were deduced to form dsRNAs as a putative target of ADAR. Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. ", "The ADAR (adenosine deaminase, RNA-specific) RNA editing enzyme controls neuronal excitability in Drosophila melanogaster.", "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster. TIRs were deduced to form dsRNAs as a putative target of ADAR. we show that expression of the editing enzyme, ADAR (adenosine deaminase acting on RNA), is dramatically decreased at elevated temperatures, partially, but not fully, explaining some target responses to temperature. ", "Adenosine-to-inosine RNA editing is a highly conserved process that post-transcriptionally modifies mRNA, generating proteomic diversity, particularly within the nervous system of metazoans. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. RNA editing by deamination of specific adenosine bases to inosines during pre-mRNA processing generates edited isoforms of proteins. RNA editing is proposed as a modulator of transcriptomes, but its biological impact has not been fully elucidated. Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts.", "adar", "RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. Adenosine-to-inosine RNA editing is a highly conserved process that post-transcriptionally modifies mRNA, generating proteomic diversity, particularly within the nervous system of metazoans.", "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. TIRs were deduced to form dsRNAs as a putative target of ADAR. ", "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. TIRs were deduced to form dsRNAs as a putative target of ADAR. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. ", "GABA inhibitory signalling is impaired in human epileptic and autistic conditions, and vertebrate ADARs may have a relevant evolutionarily conserved control over neuronal excitability. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets.", "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts." ], "exact_answer": [ "ADAR", "adenosine deaminase, RNA-specific" ], "type": "factoid", "id": "58e9e7aa3e8b6dc87c00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17018572", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 727, "text": "TIRs were deduced to form dsRNAs as a putative target of ADAR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20886259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137011", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656153", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656153", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1183, "text": "we show that expression of the editing enzyme, ADAR (adenosine deaminase acting on RNA), is dramatically decreased at elevated temperatures, partially, but not fully, explaining some target responses to temperature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25555396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137011", "endSection": "title" }, { "offsetInBeginSection": 98, "offsetInEndSection": 421, "text": "In Drosophila, many messenger RNAs involved in neuro-transmission are re-coded at the RNA level by the RNA-editing enzyme, dADAR, leading to the incorporation of amino acids that are not directly encoded by the genome. dADAR also re-codes its own transcript, but the consequences of this auto-regulation in vivo are unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Novel putative nicotinic acetylcholine receptor subunit genes, Dalpha5, Dalpha6 and Dalpha7, in Drosophila melanogaster identify a new and highly conserved target of adenosine deaminase acting on RNA-mediated A-to-I pre-mRNA editing", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11973307", "endSection": "title" }, { "offsetInBeginSection": 268, "offsetInEndSection": 444, "text": "The genome of the fruitfly, Drosophila melanogaster, contains a single gene encoding the enzyme responsible for deamination, termed ADAR (for adenosine deaminase acting on RNA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662845", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 852, "text": "Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their\u00a0mRNA isoforms. circRNA expression correlated\u00a0negatively with expression of the RNA-editing enzyme ADAR1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25921068", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 913, "text": "While several ADAR enzymes are present in mice, the presence of a single ADAR in Drosophila, combined with the diverse genetic toolkit available to researchers and the wide range of ADAR target mRNAs identified to date, make Drosophila an ideal organism to study the genetic basis of A-to-I RNA editing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662845", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 536, "text": "Aside from their role in generating protein diversity in the central nervous system, ADARs have been implicated in the hypermutation of some RNA viruses, although why this hypermutation occurs is not well understood.Here we describe the hypermutation of adenosines to guanosines in the genome of the sigma virus--a negative sense RNA virus that infects Drosophila melanogaster", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19941656", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 445, "text": "The genome of the fruitfly, Drosophila melanogaster, contains a single gene encoding the enzyme responsible for deamination, termed ADAR (for adenosine deaminase acting on RNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662845", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 979, "text": "The enzyme has no activity on dsRNA substrates but is a tRNA deaminase with specificity for adenosine 37 of insect alanine tRNA. dADAT1 shows greater similarity to vertebrate ADARs than to yeast Tad1p, supporting the hypothesis of a common evolutionary origin for ADARs and ADATs. dAdat1 transcripts are maternally supplied in the egg.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10629039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24137011", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656153", "endSection": "title" }, { "offsetInBeginSection": 377, "offsetInEndSection": 538, "text": "Here we describe the hypermutation of adenosines to guanosines in the genome of the sigma virus--a negative sense RNA virus that infects Drosophila melanogaster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19941656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The RNA editing enzyme ADAR chemically modifies adenosine (A) to inosine (I), which is interpreted by the ribosome as a guanosine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22658416", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 316, "text": "In Drosophila, many messenger RNAs involved in neuro-transmission are re-coded at the RNA level by the RNA-editing enzyme, dADAR, leading to the incorporation of amino acids that are not directly encoded by the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Drosophila melanogaster has a single Adar gene encoding a protein related to mammalian ADAR2 that edits transcripts encoding glutamate receptor subunits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761288", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 914, "text": "While several ADAR enzymes are present in mice, the presence of a single ADAR in Drosophila, combined with the diverse genetic toolkit available to researchers and the wide range of ADAR target mRNAs identified to date, make Drosophila an ideal organism to study the genetic basis of A-to-I RNA editing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17662845", "endSection": "abstract" } ] }, { "body": "What is the CEGA catalog?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26527719" ], "ideal_answer": [ "CEGA is a catalog of conserved elements from genomic alignments. Harnessing the power of multiple species comparisons to detect genomic elements under purifying selection, CEGA provides a comprehensive set of CNCs identified at different radiations along the vertebrate lineage. Evolutionary constraint is identified using threshold-free phylogenetic modeling of unbiased and sensitive global alignments of genomic synteny blocks identified using protein orthology. The dynamic CEGA web interface displays alignments, genomic locations, as well as biologically relevant data to help prioritize and select CNCs of interest for further functional investigations." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017124" ], "type": "summary", "id": "5880a46d3d0145644d000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "CEGA--a catalog of conserved elements from genomic alignments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527719", "endSection": "title" }, { "offsetInBeginSection": 712, "offsetInEndSection": 1830, "text": "To facilitate the study of such CNCs/UCEs, we present our resource of Conserved Elements from Genomic Alignments (CEGA), accessible from http://cega.ezlab.org. Harnessing the power of multiple species comparisons to detect genomic elements under purifying selection, CEGA provides a comprehensive set of CNCs identified at different radiations along the vertebrate lineage. Evolutionary constraint is identified using threshold-free phylogenetic modeling of unbiased and sensitive global alignments of genomic synteny blocks identified using protein orthology. We identified CNCs independently for five vertebrate clades, each referring to a different last common ancestor and therefore to an overlapping but varying set of CNCs with 24 488 in vertebrates, 241 575 in amniotes, 709 743 in Eutheria, 642 701 in Boreoeutheria and 612 364 in Euarchontoglires, spanning from 6 Mbp in vertebrates to 119 Mbp in Euarchontoglires. The dynamic CEGA web interface displays alignments, genomic locations, as well as biologically relevant data to help prioritize and select CNCs of interest for further functional investigations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527719", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 868, "text": "To facilitate the study of such CNCs/UCEs, we present our resource of Conserved Elements from Genomic Alignments (CEGA), accessible from http://cega.ezlab.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527719", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 870, "text": "To facilitate the study of such CNCs/UCEs, we present our resource of Conserved Elements from Genomic Alignments (CEGA), accessible from http://cega.ezlab.org", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "CEGA--a catalog of conserved elements from genomic alignments", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527719", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "CEGA--a catalog of conserved elements from genomic alignments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527719", "endSection": "title" }, { "offsetInBeginSection": 712, "offsetInEndSection": 871, "text": "To facilitate the study of such CNCs/UCEs, we present our resource of Conserved Elements from Genomic Alignments (CEGA), accessible from http://cega.ezlab.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527719", "endSection": "abstract" } ] }, { "body": "Which protein is associated with hyperemesis gravidarum during pregrancy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25963653", "http://www.ncbi.nlm.nih.gov/pubmed/20735820", "http://www.ncbi.nlm.nih.gov/pubmed/11380287", "http://www.ncbi.nlm.nih.gov/pubmed/21360554" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0020450", "o": "http://linkedlifedata.com/resource/umls/label/A18647822" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18647822", "o": "gravidarum hyperemesis" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0020450", "o": "http://linkedlifedata.com/resource/umls/label/A18610602" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18610602", "o": "excessive vomiting in pregnancy" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0020450", "o": "Hyperemesis Gravidarum" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0020450", "o": "http://linkedlifedata.com/resource/umls/label/A18666384" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18666384", "o": "hyperemesis gravidarum" } ], "ideal_answer": [ "Human chorionic gonadotropin (hCG) is associated with hyperemesis gravidarum during pregrancy." ], "exact_answer": [ "Human chorionic gonadotropin", "hCG" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014839", "http://www.disease-ontology.org/api/metadata/DOID:1832", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006939", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018997", "http://www.disease-ontology.org/api/metadata/DOID:9357" ], "type": "factoid", "id": "58da1aa08acda34529000012", "snippets": [ { "offsetInBeginSection": 1105, "offsetInEndSection": 1246, "text": "Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "First trimester maternal serum PAPP-A and free \u03b2-HCG levels in hyperemesis gravidarum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21360554", "endSection": "title" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1043, "text": "HG is associated with elevated levels of PAPP-A and free \u03b2-hCG, and such changes are independent of serum indicators of thyroid and liver function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21360554", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 1133, "text": "hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20735820", "endSection": "abstract" } ] }, { "body": "Is hydroxyurea usually used to treated infectious disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21196716", "http://www.ncbi.nlm.nih.gov/pubmed/26275071", "http://www.ncbi.nlm.nih.gov/pubmed/27677923", "http://www.ncbi.nlm.nih.gov/pubmed/15307105", "http://www.ncbi.nlm.nih.gov/pubmed/20008183" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0020402", "o": "hydroxyurea" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0020402", "o": "http://linkedlifedata.com/resource/umls/label/A0481276" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0481276", "o": "hydroxyurea" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0020402", "o": "http://linkedlifedata.com/resource/umls/label/A7996376" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7996376", "o": "hydroxyurea" } ], "ideal_answer": [ "Hydroxyurea represents the only available disease-modifying therapy for Sickle Cell Anemia (SCA)." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10923", "http://www.biosemantics.org/jochem#4275774", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4275774", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006450", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000755", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006918" ], "type": "yesno", "id": "58dbbdac8acda3452900001e", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 294, "text": "Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275071", "endSection": "abstract" }, { "offsetInBeginSection": 1579, "offsetInEndSection": 1777, "text": "In conclusion, the data here presented suggests that hydroxyurea may prevent priapism attacks in sickle cell disease, probably at higher doses than usually prescribed for painful crisis prevention..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15307105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Clinical follow-up of hydroxyurea-treated adults with sickle cell disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196716", "endSection": "title" }, { "offsetInBeginSection": 405, "offsetInEndSection": 546, "text": "t may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27677923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Hydroxyurea is one of the most successfully used therapies for sickle cell disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15307105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Clinical experience with hydroxyurea for patients with sickle cell disease (SCD) has been accumulating for the past 25 years. The bulk of the current evidence suggests that hydroxyurea is well-tolerated, safe, and efficacious for most patients with SCD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20008183", "endSection": "abstract" } ] }, { "body": "What is magnetoreception?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25551148", "http://www.ncbi.nlm.nih.gov/pubmed/25535848", "http://www.ncbi.nlm.nih.gov/pubmed/26727944", "http://www.ncbi.nlm.nih.gov/pubmed/26953690", "http://www.ncbi.nlm.nih.gov/pubmed/26811445", "http://www.ncbi.nlm.nih.gov/pubmed/27614751", "http://www.ncbi.nlm.nih.gov/pubmed/27216936" ], "ideal_answer": [ "Magnetoreception is an enigmatic, poorly understood sensory ability, described mainly on the basis of behavioural studies in animals of diverse taxa. The ability to perceive geomagnetic fields (GMFs) represents a fascinating biological phenomenon. Studies on transgenic flies have provided evidence that photosensitive Cryptochromes (Cry) are involved in the response to magnetic fields (MFs). The photoreceptor protein cryptochrome is thought to host, upon light absorption, a radical pair that is sensitive to very weak magnetic fields, endowing migratory birds with a magnetic compass sense." ], "type": "summary", "id": "58ea6c3eeda5a57672000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "The ability to perceive geomagnetic fields (GMFs) represents a fascinating biological phenomenon. Studies on transgenic flies have provided evidence that photosensitive Cryptochromes (Cry) are involved in the response to magnetic fields (MFs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26811445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Cryptochromes, blue-light absorbing proteins involved in the circadian clock, have been proposed to be the receptor molecules of the avian magnetic compass. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26953690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Although it has been known for almost half a century that migratory birds can detect the direction of the Earth's magnetic field, the primary sensory mechanism behind this remarkable feat is still unclear. The leading hypothesis centers on radical pairs-magnetically sensitive chemical intermediates formed by photoexcitation of cryptochrome proteins in the retina. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27216936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Biogenic magnetic particles have been detected in some migratory insects, which implies the basis of magnetoreception mechanism for orientation and navigation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26727944", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Magnetoreception is essential for magnetic orientation in animal migration. The molecular basis for magnetoreception has recently been elucidated in fruitfly as complexes between the magnetic receptor magnetoreceptor (MagR) and its ligand cryptochrome (Cry). MagR and Cry are present in the animal kingdom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27614751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Magnetoreception is an enigmatic, poorly understood sensory ability, described mainly on the basis of behavioural studies in animals of diverse taxa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25551148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The photoreceptor protein cryptochrome is thought to host, upon light absorption, a radical pair that is sensitive to very weak magnetic fields, endowing migratory birds with a magnetic compass sense.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25535848", "endSection": "abstract" } ] }, { "body": "Can acupuncture cause spinal epidural hematoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27651774", "http://www.ncbi.nlm.nih.gov/pubmed/8456713", "http://www.ncbi.nlm.nih.gov/pubmed/25459742", "http://www.ncbi.nlm.nih.gov/pubmed/21082060", "http://www.ncbi.nlm.nih.gov/pubmed/21289580", "http://www.ncbi.nlm.nih.gov/pubmed/24094991" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0394664", "o": "Acupuncture" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0394664", "o": "http://linkedlifedata.com/resource/umls/label/A0472806" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0472806", "o": "acupuncture" } ], "ideal_answer": [ "Yes, acupuncture can cause spinal epidural hematoma." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046748", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026881" ], "type": "yesno", "id": "5890e762621ea6ff7e000005", "snippets": [ { "offsetInBeginSection": 649, "offsetInEndSection": 939, "text": "RESULTS: A 54-year-old woman, a 38-year-old woman, and a 60-year-old man with hemiplegia by cervical subdural or epidural hematoma after cervical posterior paraspinal muscle needling without direct invasion (intramuscular stimulation, acupuncture, or intramuscular lidocaine) were observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25459742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Acute spinal subdural hematoma with hemiplegia after acupuncture: a case report and review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24094991", "endSection": "title" }, { "offsetInBeginSection": 174, "offsetInEndSection": 482, "text": "Although acupuncture has been a popular method for the management of pain control, we encountered the first case of SDH after acupuncture.PURPOSE: The purpose of this case report was to present the first case of subdural hematoma after acupuncture and the reasons for the risks of blind cervical acupuncture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24094991", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 317, "text": "SUMMARY OF BACKGROUND DATA: Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21289580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21082060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21082060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456713", "endSection": "title" }, { "offsetInBeginSection": 69, "offsetInEndSection": 199, "text": "However, subarachnoid hemorrhage and spinal epidural hematoma have been reported to occur after acupuncture in the posterior neck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27651774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "A retrospective case report.The objective of this article is to report an unusual complication of dry needling.Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21289580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456713", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21082060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456713", "endSection": "title" } ] }, { "body": "Is edema a symptom of nephrotic syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17448310", "http://www.ncbi.nlm.nih.gov/pubmed/20368913", "http://www.ncbi.nlm.nih.gov/pubmed/10884998", "http://www.ncbi.nlm.nih.gov/pubmed/17111701", "http://www.ncbi.nlm.nih.gov/pubmed/10361423", "http://www.ncbi.nlm.nih.gov/pubmed/15852660", "http://www.ncbi.nlm.nih.gov/pubmed/16247647", "http://www.ncbi.nlm.nih.gov/pubmed/9241903", "http://www.ncbi.nlm.nih.gov/pubmed/19556043", "http://www.ncbi.nlm.nih.gov/pubmed/21234253", "http://www.ncbi.nlm.nih.gov/pubmed/21302208", "http://www.ncbi.nlm.nih.gov/pubmed/24240509", "http://www.ncbi.nlm.nih.gov/pubmed/21454171", "http://www.ncbi.nlm.nih.gov/pubmed/17009081", "http://www.ncbi.nlm.nih.gov/pubmed/26457719", "http://www.ncbi.nlm.nih.gov/pubmed/26281851", "http://www.ncbi.nlm.nih.gov/pubmed/25722313", "http://www.ncbi.nlm.nih.gov/pubmed/23529637", "http://www.ncbi.nlm.nih.gov/pubmed/11928729", "http://www.ncbi.nlm.nih.gov/pubmed/12508485", "http://www.ncbi.nlm.nih.gov/pubmed/26178548", "http://www.ncbi.nlm.nih.gov/pubmed/24533195", "http://www.ncbi.nlm.nih.gov/pubmed/10215332", "http://www.ncbi.nlm.nih.gov/pubmed/25400184", "http://www.ncbi.nlm.nih.gov/pubmed/20924604", "http://www.ncbi.nlm.nih.gov/pubmed/19194561", "http://www.ncbi.nlm.nih.gov/pubmed/1953084", "http://www.ncbi.nlm.nih.gov/pubmed/23510630" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0027726", "o": "Nephrotic Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0027726", "o": "http://linkedlifedata.com/resource/umls/label/A0484584" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0484584", "o": "nephrotic syndrome" } ], "ideal_answer": [ "Yes, edema is the commonest presenting symptom and sign in nephrotic syndrome." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004487", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009404", "http://www.disease-ontology.org/api/metadata/DOID:1184" ], "type": "yesno", "id": "58da270d8acda34529000013", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 192, "text": "Nephrotic syndrome (NS) is a common clinical disease with four main clinical manifestations: hypoalbuminemia (<30 g/L), macro-proteinuria (>3.5 g/24 h), edema, and hyperlipidemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26281851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19194561", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 355, "text": "Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19194561", "endSection": "abstract" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1406, "text": "The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19194561", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 755, "text": "Most patients presented within 3 months duration (61.4%) and the most common symptom was puffiness of face (98.45%) followed by pedal edema (91%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20368913", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 381, "text": "We analyzed medical records of 290 patients with diagnosis of nephrotic syndrome as defined by International Study of Kidney Disease in Children (ISKDC), between January 1987 and December 2000, at the Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20368913", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 402, "text": "He was admitted because of systemic edema and dyspnea on effort Laboratory data revealed renal failure and nephrotic syndrome, whereas there was no symptom of diabetic retinopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15852660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Nephrotic syndrome: more than just oedema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11928729", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Oedema is the commonest presenting symptom and sign in nephrotic syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11928729", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 428, "text": "One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21302208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Tolvaptan therapy for massive edema in a patient with nephrotic syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240509", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Nephrotic syndrome (NS) is characterized by water and sodium retention, which leads to edema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240509", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 555, "text": "The non-osmotic stimulation of arginine vasopressin release from the pituitary gland has been implicated as one of the important factors in abnormal water retention in patients with NS.We present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist.Tolvaptan is effective for the treatment of massive edema caused by NS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240509", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 487, "text": "We report a child with steroid-resistant nephrotic syndrome with diuretic-resistant nephrotic edema treated successfully using acute peritoneal dialysis as a means of UF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26178548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Albumin and Furosemide Combination for Management of Edema in Nephrotic Syndrome: A Review of Clinical Studies", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26457719", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26457719", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 858, "text": "Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20924604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23529637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "The nephrotic syndrome is characterized by a combination of pathological lab values and clinical symptoms, i. e. pronounced proteinuria (usually more than 3 - 3,5 g protein/24 h), hypoalbuminemia, edema and hyperlipidemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25722313", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 365, "text": "The patient was admitted with edema of both legs, and the nephrotic syndrome was discovered, leading to the diagnosis of AA amyloidosis on kidney biopsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17111701", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 1086, "text": "Linear regression to relate measures.Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19556043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "A case of interstitial shadows associated with oral cyclophosphamide therapy in a 32-month-old girl with steroid-resistant nephrotic syndrome, who was admitted to the Nishi-Kobe Medical Center with systemic edema, is reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9241903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Nephrotic syndrome represents a constellation of symptoms including hyperalbuminuria, hypoalbuminemia, edema formation, hypercholesterolemia, hypertension, hypercoagulopathy, and increased infection risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10884998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10215332", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "To study the evidence-based therapy of edema in nephrotic syndrome by analyzing the literatures systematically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17448310", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 362, "text": "Edema is the prominent feature of nephrotic syndrome and initially develops around the eyes and legs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21454171", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 611, "text": "Intussusception should be considered in the differential diagnosis of abdominal pain in patients with nephrotic syndrome, especially in patients exhibiting prolonged edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16247647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Oedema is the commonest presenting symptom and sign in nephrotic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11928729", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 1090, "text": "Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19556043", "endSection": "abstract" } ] }, { "body": "Angelman syndrome is associated with deletion of a part of Chromosome 15 but if the deletion occurs in the paternally inherited chromosome 15, what is the disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26713299", "http://www.ncbi.nlm.nih.gov/pubmed/1714232", "http://www.ncbi.nlm.nih.gov/pubmed/2564739", "http://www.ncbi.nlm.nih.gov/pubmed/1985457", "http://www.ncbi.nlm.nih.gov/pubmed/2309781" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0008657", "o": "http://linkedlifedata.com/resource/umls/label/A18664896" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18664896", "o": "chromosome 15" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0008657", "o": "Chromosomes, Human, Pair 15" } ], "ideal_answer": [ "Prader-Willi syndrome (PWS) results from a deletion of the paternal genes in the region of chromosome 15q11-q13.", " prader-willi syndrome (pws) results from a deletion of the paternal genes in the region of chromosome 15q11-q13.", "Prader-Willi syndrome (PWS) results from a deletion of the paternal genes in the region of chromosome 15q11-q13. ", " Prader-Willi syndrome (PWS) results from a deletion of the paternal genes in the region of chromosome 15q11-q13." ], "exact_answer": [ "Prader-Willi syndrome" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002872", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D025063", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011218", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002901", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017353" ], "type": "factoid", "id": "58e3d9ab3e8b6dc87c000002", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 124, "text": " Prader-Willi syndrome (PWS) results from a deletion of the paternal genes in the region of chromosome 15q11-q13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26713299", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 575, "text": "In AS, the deletion occurs in the maternally inherited chromosome 15, while in PWS the deletion is found in the paternally inherited chromosome 15.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1985457", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 577, "text": "In AS, the deletion occurs in the maternally inherited chromosome 15, while in PWS the deletion is found in the paternally inherited chromosome 15", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1985457", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 578, "text": "In AS, the deletion occurs in the maternally inherited chromosome 15, while in PWS the deletion is found in the paternally inherited chromosome 15.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1985457", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 452, "text": "However, deletions in AS occur on the maternally inherited chromosome 15, and deletions in PWS occur on the paternally derived chromosome 15.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1714232", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 630, "text": "This contrasts with the Prader-Willi syndrome (PWS) in which a similar deletion of the paternally contributed chromosome 15 is observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2309781", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 563, "text": "However, in contrast to the paternal inheritance of the deleted chromosome 15 observed in the majority of PWS patients, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2564739", "endSection": "abstract" } ] }, { "body": "What is the phenotype of people carrying mutations in the gene PRDM12?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25891934", "http://www.ncbi.nlm.nih.gov/pubmed/26005867", "http://www.ncbi.nlm.nih.gov/pubmed/26549885" ], "ideal_answer": [ "New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families." ], "exact_answer": [ "congenital insensitivity to pain", "CIP" ], "type": "factoid", "id": "58ea7248eda5a57672000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25891934", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 396, "text": "Here we show that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25891934", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Transcriptional regulator PRDM12 is essential for human pain perception.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26005867", "endSection": "title" }, { "offsetInBeginSection": 276, "offsetInEndSection": 673, "text": " New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26005867", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 592, "text": " However, the study of genetic disorders rendering individuals completely unable to feel pain offers hope. All causes of congenital painlessness affect nociceptors, evolutionarily conserved specialist neurons able to sense all type of tissue damage. The discovery of new genes essential for sensing pain (SCN11A, PRDM12, and CLTCL1) has provided unexpected insights into the biological mechanisms that drive distinct stages of nociception.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26549885", "endSection": "abstract" } ] }, { "body": "Is there an association between Histone H3.3 mutations and glioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22286061", "http://www.ncbi.nlm.nih.gov/pubmed/24229707", "http://www.ncbi.nlm.nih.gov/pubmed/25281433", "http://www.ncbi.nlm.nih.gov/pubmed/23429371", "http://www.ncbi.nlm.nih.gov/pubmed/27392443", "http://www.ncbi.nlm.nih.gov/pubmed/25219808", "http://www.ncbi.nlm.nih.gov/pubmed/24691963", "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "http://www.ncbi.nlm.nih.gov/pubmed/26517431", "http://www.ncbi.nlm.nih.gov/pubmed/25976256", "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "http://www.ncbi.nlm.nih.gov/pubmed/25200322", "http://www.ncbi.nlm.nih.gov/pubmed/24285547", "http://www.ncbi.nlm.nih.gov/pubmed/24622842", "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "http://www.ncbi.nlm.nih.gov/pubmed/27864305", "http://www.ncbi.nlm.nih.gov/pubmed/24997139", "http://www.ncbi.nlm.nih.gov/pubmed/23417712", "http://www.ncbi.nlm.nih.gov/pubmed/23603901" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0017638", "o": "Glioma" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0026882", "o": "mutation" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0026882", "o": "http://linkedlifedata.com/resource/umls/label/A18555731" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18555731", "o": "mutation" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0596306", "o": "Association" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0026882", "o": "http://linkedlifedata.com/resource/umls/label/A18667225" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18667225", "o": "mutations" } ], "ideal_answer": [ "Yes, histone H3.3 mutation in the codon for lysine 27 has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/H33_VITVI", "http://www.uniprot.org/uniprot/H33_BOVIN", "http://www.uniprot.org/uniprot/H33_TETTS", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001244", "http://www.uniprot.org/uniprot/H33_LOLMU", "http://www.uniprot.org/uniprot/H33_CHICK", "http://www.uniprot.org/uniprot/H33_MEDSA", "http://www.uniprot.org/uniprot/H33_SPISO", "http://www.uniprot.org/uniprot/H33_TRIPS", "http://www.uniprot.org/uniprot/H33_TOBAC", "http://www.uniprot.org/uniprot/H33_TETPY", "http://www.uniprot.org/uniprot/H33_XENLA", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005910", "http://www.uniprot.org/uniprot/H33_ARATH", "http://www.uniprot.org/uniprot/H33_XENTR" ], "type": "yesno", "id": "5890ede0621ea6ff7e000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 522, "text": "PURPOSE: Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27392443", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1470, "text": "CONCLUSION: This report demonstrates minute neuroradiological and pathological features of malignant transformation from thalamic low grade glioma with H3F3A K27M mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27392443", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 651, "text": "Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78\u00a0% of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36\u00a0% of non-brainstem gliomas carrying either K27M or G34R/V mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773741", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 751, "text": "The pathological diagnosis was anaplastic oligodendroglioma, and we identified a mutation in histone H3.3 in the tumor specimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25281433", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1301, "text": "CONCLUSIONS: Pediatric brainstem oligodendroglial tumors can include histone H3.3-mutated tumors and have a tendency to disseminate throughout the neuroaxis at the time of relapse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25281433", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 765, "text": "We highlight the genetic aberrations recently discovered in isocitrate dehydrogenase, alpha thalassemia/mental retardation syndrome X-linked, death-domain-associated protein, histone H3.3, and telomerase reverse transcriptase and discuss how these mutations lead to unexpected changes in the epigenetic landscape in gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25976256", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1194, "text": "Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24622842", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 454, "text": "Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23603901", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24997139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Mutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24285547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Somatic mutations of the H3F3A and HIST1H3B genes encoding the histone H3 variants, H3.3 and H3.1, were recently identified in high-grade gliomas arising in the thalamus, pons and spinal cord of children and young adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26517431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661320", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Recurrent mutations affecting the histone H3.3 residues Lys27 or indirectly Lys36 are frequent drivers of pediatric high-grade gliomas (over 30% of HGGs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23417712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525250", "endSection": "title" }, { "offsetInBeginSection": 72, "offsetInEndSection": 241, "text": "Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23907119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22286061", "endSection": "title" } ] }, { "body": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22438832", "http://www.ncbi.nlm.nih.gov/pubmed/26728715", "http://www.ncbi.nlm.nih.gov/pubmed/15777722", "http://www.ncbi.nlm.nih.gov/pubmed/12702877", "http://www.ncbi.nlm.nih.gov/pubmed/22265405" ], "ideal_answer": [ "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. ", "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase. Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. They both bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins.", "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Here we describe the remaining two genes, fhl1 and fkh2, that code for proteins containing fork-head-associated domains (FHA) besides their FKHs. This may reflect a general feature of gene regulation in eukaryotes. ", "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.", "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. ", "Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.", "Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan.", "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing." ], "exact_answer": [ "DNA replication" ], "type": "factoid", "id": "58eb4ce7eda5a57672000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22265405", "endSection": "title" }, { "offsetInBeginSection": 335, "offsetInEndSection": 463, "text": "Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22265405", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 938, "text": "Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22265405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. A key function in this process involves the regulation of the cell cycle and stress responses including free radical scavenging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438832", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 761, "text": "We report that the deletion of both FKH genes impedes normal lifespan and stress resistance, particularly in stationary phase cells, which are non-responsive to caloric restriction. Conversely, increased expression of the FKHs leads to extended lifespan and improved stress response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438832", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1471, "text": "This study establishes the FKHs role as evolutionarily conserved regulators of lifespan in yeast and identifies the APC as a novel component of this mechanism under certain conditions, likely through combined regulation of stress response, genomic stability, and cell cycle regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438832", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 633, "text": "The genome of Schizosaccharomyces pombe has four genes that code for proteins containing fork-head domains (FKH), two of which have been characterised. Here we describe the remaining two genes, fhl1 and fkh2, that code for proteins containing fork-head-associated domains (FHA) besides their FKHs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15777722", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 466, "text": "Here we show that the yeast forkhead transcription factors, Fkh1p and Fkh2p, associate with the coding regions of active genes and influence, in opposing ways, transcriptional elongation and termination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12702877", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 830, "text": "Our results suggest that, in addition to their documented promoter function, Fkh1p and Fkh2p coordinate early transcription elongation and pre-mRNA processing. This may reflect a general feature of gene regulation in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12702877", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 461, "text": "Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22265405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "The Saccharomyces cerevisiae Forkhead Box (FOX) proteins, Fkh1 and Fkh2, regulate diverse cellular processes including transcription, long-range DNA interactions during homologous recombination, and replication origin timing and long-range origin clustering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26728715", "endSection": "abstract" } ] }, { "body": "What is the role of the Ctf4-interacting-peptide or CIP-box?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27397685" ], "ideal_answer": [ "Crystallographic analysis classifies CIP-boxes into two related groups that target different sites on Ctf4. Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome-wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats. Data reveal unexpected complexity of Ctf4 function, as a hub that connects multiple accessory factors to the replisome. Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation." ], "concepts": [ "http://www.biosemantics.org/jochem#4264134", "http://www.biosemantics.org/jochem#4265011" ], "type": "summary", "id": "58815f26713cbdfd3d000002", "snippets": [ { "offsetInBeginSection": 264, "offsetInEndSection": 1010, "text": " Here, we identify new Ctf4 partners in\u00a0addition to Pol \u03b1 and helicase, all of which contain a \"Ctf4-interacting-peptide\" or CIP-box. Crystallographic analysis classifies CIP-boxes into two related groups that target different sites on Ctf4. Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome-wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats. Our data reveal unexpected complexity of Ctf4 function, as a hub that connects multiple accessory factors to the replisome. Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27397685", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 738, "text": "Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome-wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27397685", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 742, "text": "Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome-wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27397685", "endSection": "abstract" } ] }, { "body": "What type of genome, (RNA or DNA, double stranded single stranded) is found in the the virus that causes blue tongue disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22549161" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0042776", "o": "http://linkedlifedata.com/resource/umls/label/A0491591" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0491591", "o": "virus" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0319157", "o": "virus" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0042776", "o": "Viruses" } ], "ideal_answer": [ "The Bluetongue virus (BTV) genome contains ten double-stranded RNA segments.", "Bluetongue virus (BTV) genome contains ten double-stranded RNA segments. ", "Bluetongue virus (BTV) genome contains ten double-stranded RNA segments.", "Bluetongue virus (BTV) genome contains ten double-stranded RNA segments", "bluetongue virus (btv) genome contains ten double-stranded rna segments." ], "exact_answer": [ "double stranded, segmented RNA" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1301", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001820", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012330", "http://www.disease-ontology.org/api/metadata/DOID:0050498" ], "type": "factoid", "id": "58f3c4b970f9fc6f0f00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Bluetongue virus (BTV) genome contains ten double-stranded RNA segments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22549161", "endSection": "abstract" } ] }, { "body": "What is a \"chemobrain\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25176562", "http://www.ncbi.nlm.nih.gov/pubmed/26653737", "http://www.ncbi.nlm.nih.gov/pubmed/25687405", "http://www.ncbi.nlm.nih.gov/pubmed/27041861", "http://www.ncbi.nlm.nih.gov/pubmed/27709283" ], "ideal_answer": [ "The term \"chemobrain\" is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment." ], "exact_answer": [ "The term \"chemobrain\" is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment." ], "type": "factoid", "id": "58efa1b870f9fc6f0f000003", "snippets": [ { "offsetInBeginSection": 322, "offsetInEndSection": 563, "text": "Frequency of chemotherapy-related cognitive impairment or \"chemobrain\" is mentioned to be significant in literature, although very little is known about the chemotherapy-caused chemobrain and its connection with metal homeostasis alteration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653737", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 185, "text": "Cognitive decline or dementia is a debilitating problem of neurological disorders such as Alzheimer's and Parkinson's disease, including special conditions like chemobrain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27041861", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 219, "text": "Most cancer patients treated with systemic adjuvant chemotherapy endure long-lasting side effects including decrease in concentration, forgetfulness and slower thinking, which are globally termed \"chemobrain.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "The frequent use of chemotherapy to combat a range of malignancies can elicit severe cognitive dysfunction often referred to as \"chemobrain,\" a condition that can persist long after the cessation of treatment in as many as 75% of survivors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687405", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 150, "text": "The term \"chemobrain\" is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25176562", "endSection": "abstract" } ] }, { "body": "Borden classification is used for which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22107858", "http://www.ncbi.nlm.nih.gov/pubmed/20678361", "http://www.ncbi.nlm.nih.gov/pubmed/20678360", "http://www.ncbi.nlm.nih.gov/pubmed/22374275", "http://www.ncbi.nlm.nih.gov/pubmed/23582488", "http://www.ncbi.nlm.nih.gov/pubmed/23570149", "http://www.ncbi.nlm.nih.gov/pubmed/25479123", "http://www.ncbi.nlm.nih.gov/pubmed/23811958", "http://www.ncbi.nlm.nih.gov/pubmed/20966056", "http://www.ncbi.nlm.nih.gov/pubmed/20176602", "http://www.ncbi.nlm.nih.gov/pubmed/20849795", "http://www.ncbi.nlm.nih.gov/pubmed/25516093", "http://www.ncbi.nlm.nih.gov/pubmed/25746311", "http://www.ncbi.nlm.nih.gov/pubmed/25354667", "http://www.ncbi.nlm.nih.gov/pubmed/15842944", "http://www.ncbi.nlm.nih.gov/pubmed/26246101", "http://www.ncbi.nlm.nih.gov/pubmed/8893721", "http://www.ncbi.nlm.nih.gov/pubmed/26120845", "http://www.ncbi.nlm.nih.gov/pubmed/16286391", "http://www.ncbi.nlm.nih.gov/pubmed/19408992" ], "ideal_answer": [ "Borden classification systems is used for the prediction of clinical behavior of cranial dural arteriovenous fistulas." ], "exact_answer": [ "cranial dural arteriovenous fistula", "DAVF" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002965", "http://www.disease-ontology.org/api/metadata/DOID:4", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category" ], "type": "factoid", "id": "5890fde5621ea6ff7e000009", "snippets": [ { "offsetInBeginSection": 277, "offsetInEndSection": 545, "text": "The locations of DAVFs were the transverse-sigmoid sinus in 11, tentorium in 10, cranial vault in 9, and superior sagittal sinus, jugular bulb, foramen magnum, and middle cranial fossa in 1 each. Borden classification was type I in 7, type II in 3, and type III in 24.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25746311", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1236, "text": "Transarterial glue embolization is highly effective for Borden type III DAVF with direct cortical venous drainage, but has limitations for Borden type I and II DAVFs in which the affected sinus is part of the normal venous circulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25746311", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1082, "text": "The results of subtype (Borden and Cognard classification), venous reflux and fistula sites were also accurately exhibited in 4D-CTA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25354667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "The commonly used Borden and Cognard classification systems for the prediction of clinical behavior of cranial dural arteriovenous shunts focus on the venous drainage, particularly the presence of leptomeningeal venous drainage, and on the direction of flow, particularly the presence of retrograde flow. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516093", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 527, "text": "The CS DAVFs and the NCS DAVFs were categorized using the Barrow and Borden classification systems, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479123", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 388, "text": "The two most commonly used and clinically accepted DAVF classifications are the Merland-Cognard classification and the Borden classification, both based on the morphology of the venous drainage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22107858", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1371, "text": "When analyzed according to the Borden classification, none (0%) of 55 Type I intracranial dural AVFs, two (11%) of 18 Type II, and 14 (48%) of 29 Type III intracranial dural AVFs presented with hemorrhage (p < 0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8893721", "endSection": "abstract" }, { "offsetInBeginSection": 2651, "offsetInEndSection": 2855, "text": "The configuration of venous anatomy as reflected by both the Cognard and Borden classifications strongly predicts intracranial dural AVFs that will present with ICH or nonhemorrhagic neurological deficit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8893721", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 388, "text": "The two most commonly used and clinically accepted DAVF classifications are the Merland-Cognard classification and the Borden classification, both based on the morphology of the venous drainage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22107858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "The commonly used Borden and Cognard classification systems for the prediction of clinical behavior of cranial dural arteriovenous shunts focus on the venous drainage, particularly the presence of leptomeningeal venous drainage, and on the direction of flow, particularly the presence of retrograde flow", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516093", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1383, "text": "When analyzed according to the Borden classification, none (0%) of 55 Type I intracranial dural AVFs, two (11%) of 18 Type II, and 14 (48%) of 29 Type III intracranial dural AVFs presented with hemorrhage (p < 0.0001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8893721", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 587, "text": "Borden classification showed Type III in 1 and Type II in 10 ncsDAVFs, and Type II in 4 and Type I in 6 csDAVFs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "The recently proposed classification scheme of Borden, Wu, and Shucart (Borden(*)) should have the ability to identify those intracranial dural arteriovenous fistulae (ICDAVF) which will continue to behave in a benign fashion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20678360", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 389, "text": "The two most commonly used and clinically accepted DAVF classifications are the Merland-Cognard classification and the Borden classification, both based on the morphology of the venous drainage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22107858", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 510, "text": "The CS DAVFs and the NCS DAVFs were categorized using the Barrow and Borden classification systems, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479123", "endSection": "abstract" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1623, "text": "A multivariate logistic regression model showed that intracranial hemorrhage in patients with DAVFs was correlated with higher Borden classification (OR 5.880; 95% CI, 3.370-10.257; p<0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26120845", "endSection": "abstract" }, { "offsetInBeginSection": 2668, "offsetInEndSection": 2873, "text": "The configuration of venous anatomy as reflected by both the Cognard and Borden classifications strongly predicts intracranial dural AVFs that will present with ICH or nonhemorrhagic neurological deficit..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8893721", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 589, "text": "Borden classification showed Type III in 1 and Type II in 10 ncsDAVFs, and Type II in 4 and Type I in 6 csDAVFs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374275", "endSection": "abstract" } ] }, { "body": "Which effects create neighborhoods of transcriptional regulation in eukaryotes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22084256", "http://www.ncbi.nlm.nih.gov/pubmed/27799341", "http://www.ncbi.nlm.nih.gov/pubmed/17025153" ], "ideal_answer": [ "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes. Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. we find that the transcription of gene neighbors is correlated over distances that scale with genome size. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation. ", "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions.", " we propose that enhancer sharing is commonplace among eukaryotes, and that ep distance is an important layer of information in gene regulation.", "Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation.", "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes", "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation." ], "exact_answer": [ "the sharing of enhancer elements", "enhancer sharing" ], "type": "factoid", "id": "58c27b7102b8c60953000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799341", "endSection": "title" }, { "offsetInBeginSection": 307, "offsetInEndSection": 471, "text": "Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799341", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 618, "text": "we find that the transcription of gene neighbors is correlated over distances that scale with genome size. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799341", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 943, "text": " We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799341", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 897, "text": "This is especially true in mammalian systems, where regulation often occurs through long-range enhancers in gene-rich neighborhoods, rather than proximal promoters, preventing straightforward assignment of a binding site to a target gene.We present EMBER (Expectation Maximization of Binding and Expression pRofiles), a method that integrates high-throughput binding data (e.g. ChIP-chip or ChIP-seq) with gene expression data (e.g. DNA microarray) via an unsupervised machine learning algorithm for inferring the gene targets of sets of TF binding sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22084256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799341", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "One of the dogmas of transcriptional regulation in higher eukaryotes suggests the existence of transcriptional domains with no promoter-enhancer interactions between them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17025153", "endSection": "abstract" } ] }, { "body": "Is Pfh1 a component of the replisome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "http://www.ncbi.nlm.nih.gov/pubmed/27611590" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1325592", "o": "replisome" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1325592", "o": "http://linkedlifedata.com/resource/umls/label/A11591254" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11591254", "o": "replisome" } ], "ideal_answer": [ "No. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity. DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase." ], "exact_answer": "no", "type": "yesno", "id": "5881e8e8713cbdfd3d000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "title" }, { "offsetInBeginSection": 288, "offsetInEndSection": 754, "text": "Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 546, "text": "Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1245, "text": " Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1102, "text": "Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "title" }, { "offsetInBeginSection": 1810, "offsetInEndSection": 1979, "text": "Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "abstract" }, { "offsetInBeginSection": 1585, "offsetInEndSection": 1810, "text": "Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1585, "text": "Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1108, "text": "Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 544, "text": "Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1244, "text": "Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1109, "text": "Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22426534", "endSection": "abstract" }, { "offsetInBeginSection": 1818, "offsetInEndSection": 1987, "text": "Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "abstract" }, { "offsetInBeginSection": 1592, "offsetInEndSection": 1817, "text": "Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611590", "endSection": "title" } ] }, { "body": "What is the function of mTOR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12864941", "http://www.ncbi.nlm.nih.gov/pubmed/21871173", "http://www.ncbi.nlm.nih.gov/pubmed/19182527", "http://www.ncbi.nlm.nih.gov/pubmed/27889578", "http://www.ncbi.nlm.nih.gov/pubmed/25898924", "http://www.ncbi.nlm.nih.gov/pubmed/25893295" ], "ideal_answer": [ "The mTOR protein regulates assembly of the translation initiation machinery and are master regulators of cellular survival, growth and metabolism." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0065009" ], "type": "summary", "id": "58f3c8f470f9fc6f0f00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Protein synthesis regulation via mammalian target of rapamycin complex 1 (mTORC1) signaling pathway has key roles in neural development and function,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25898924", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 464, "text": "mTOR regulates assembly of the translation initiation machinery by interacting with the eukaryotic initiation factor eIF3 complex and by controlling phosphorylation of key translational regulators", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25898924", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 364, "text": "Mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, are master regulators of cellular survival, growth and metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25893295", "endSection": "abstract" }, { "offsetInBeginSection": 41, "offsetInEndSection": 468, "text": " (mTOR) is a serine-threonine kinase that controls several important aspects of mammalian cell function. mTOR activity is modulated by various intra- and extracellular factors; in turn, mTOR changes rates of translation, transcription, protein degradation, cell signaling, metabolism, and cytoskeleton dynamics. mTOR has been repeatedly shown to participate in neuronal development and the proper functioning of mature neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27889578", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 167, "text": "mammalian target of rapamycin (mTOR), a member of the phosphoinositide 3-kinase related kinase (PIKK) family, plays a central role in the regulation of cell growth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19182527", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 228, "text": "(mTOR) is a serine/threonine kinase and that forms two multiprotein complexes known as the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR regulates cell growth, proliferation and survival", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21871173", "endSection": "abstract" }, { "offsetInBeginSection": 34, "offsetInEndSection": 195, "text": "(mTOR), a downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B) signaling pathway that mediates cell survival and proliferation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12864941", "endSection": "abstract" } ] }, { "body": "What is the indication for valbenazine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25809133", "http://www.ncbi.nlm.nih.gov/pubmed/27819145" ], "ideal_answer": [ "Valbenazine granted breakthrough drug status for treating tardive dyskinesia." ], "exact_answer": [ "Valbenazine granted breakthrough drug status for treating tardive dyskinesia." ], "type": "factoid", "id": "58f0b0c070f9fc6f0f000006", "snippets": [ { "offsetInBeginSection": 571, "offsetInEndSection": 747, "text": "VMAT2 inhibitors (e.g. deutetrabenazine and valbenazine) have been studied in the treatment of HD-related chorea, tardive dyskinesia and tics associated with Tourette syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27819145", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 76, "text": "Valbenazine granted breakthrough drug status for treating tardive dyskinesia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25809133", "endSection": "title" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1000, "text": "The FDA lowered approval hurdles for valbenazine due to a successful Phase II trial, which showed a distinctive improvement in tardive dyskinesia symptoms during valbenazine administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25809133", "endSection": "abstract" } ] }, { "body": "List features of the Kaufman Oculocerebrofacial Syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8275567", "http://www.ncbi.nlm.nih.gov/pubmed/23687348", "http://www.ncbi.nlm.nih.gov/pubmed/7573151", "http://www.ncbi.nlm.nih.gov/pubmed/24615390", "http://www.ncbi.nlm.nih.gov/pubmed/25691420", "http://www.ncbi.nlm.nih.gov/pubmed/25792360" ], "ideal_answer": [ "Clinical features of the Kaufman Oculocerebrofacial Syndrome include hypotonia, developmental delay, intellectual disability, low cholesterol levels, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet." ], "exact_answer": [ [ "hypotonia" ], [ "developmental delay" ], [ "intellectual disability" ], [ "low cholesterol levels" ], [ "microcephaly" ], [ "long narrow face" ], [ "ocular anomalies" ], [ "long thin hands and feet" ] ], "type": "list", "id": "5895b7157d9090f353000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "A pair of sisters was ascertained for multiple congenital defects, including marked craniofacial dysmorphisms with blepharophimosis, and severe psychomotor delay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25691420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Genetic syndromes involving both brain and eye abnormalities are numerous and include syndromes such as Warburg micro syndrome, Kaufman oculocerebrofacial syndrome, Cerebro-oculo-facio-skeletal syndrome, Kahrizi syndrome and others. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25792360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24615390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "BACKGROUND: Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23687348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder characterized by severe mental retardation, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7573151", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 299, "text": "Both showed psychomotor retardation, microcephaly, blepharophimosis and delayed growth as the main features; the infant also presented preauricular tags and large clitoris. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8275567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23687348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24615390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23687348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder characterized by severe mental retardation, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7573151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder characterized by severe mental retardation, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7573151", "endSection": "abstract" } ] }, { "body": "What is the role of DNA Repair Cofactors ATMIN and NBS1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26544571" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0012899", "o": "DNA repair" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0012899", "o": "http://linkedlifedata.com/resource/umls/label/A18609617" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18609617", "o": "dna repair" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/uniprot/O43070", "o": "http://purl.uniprot.org/uniprot/O43070" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-2125045", "o": "nbs1" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4F34333037300013", "o": "nbs1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/uniprot/O43070", "o": "NBS1_SCHPO" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/O43070", "o": "http://linkedlifedata.com/resource/#_4F34333037300013" } ], "ideal_answer": [ "The DNA double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell development and for the maintenance of genomic stability. The role of a second ATM cofactor, ATMIN (also known as ASCIZ) in T cells is much less clear, and whether ATMIN and NBS1 function in synergy in T cells is unknown.", "The DNA Repair Cofactors ATMIN and NBS1 are required to suppress T Cell activation. Loss of NBS1 led to a developmental block at the double-positive stage of T cell development, as well as reduced TCR\u03b1 recombination, that was unexpectedly neither exacerbated nor alleviated by concomitant loss of ATMIN. In contrast, loss of both ATMIN and NBS1 enhanced DNA damage that drove spontaneous peripheral T cell hyperactivation, proliferation as well as excessive production of proinflammatory cytokines and chemokines, leading to a highly inflammatory environment. Intriguingly, the disease causing T cells were largely proficient for both ATMIN and NBS1. In vivo this resulted in severe intestinal inflammation, colitis and premature death." ], "exact_answer": [ "Suppresion of T Cell Activation." ], "concepts": [ "http://www.uniprot.org/uniprot/NBS1_SCHPO", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://www.uniprot.org/uniprot/NBS1_ARATH", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053843", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045643" ], "type": "factoid", "id": "58853c56e56acf5176000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 1366, "text": "Here, we investigate the roles of ATMIN and NBS1, either alone or in combination, using murine models. We show loss of NBS1 led to a developmental block at the double-positive stage of T cell development, as well as reduced TCR\u03b1 recombination, that was unexpectedly neither exacerbated nor alleviated by concomitant loss of ATMIN. In contrast, loss of both ATMIN and NBS1 enhanced DNA damage that drove spontaneous peripheral T cell hyperactivation, proliferation as well as excessive production of proinflammatory cytokines and chemokines, leading to a highly inflammatory environment. Intriguingly, the disease causing T cells were largely proficient for both ATMIN and NBS1. In vivo this resulted in severe intestinal inflammation, colitis and premature death. Our findings reveal a novel model for an intestinal bowel disease phenotype that occurs upon combined loss of the DNA repair cofactors ATMIN and NBS1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "abstract" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1358, "text": "Our findings reveal a novel model for an intestinal bowel disease phenotype that occurs upon combined loss of the DNA repair cofactors ATMIN and NBS1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1033, "text": "In contrast, loss of both ATMIN and NBS1 enhanced DNA damage that drove spontaneous peripheral T cell hyperactivation, proliferation as well as excessive production of proinflammatory cytokines and chemokines, leading to a highly inflammatory environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "title" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1365, "text": "Our findings reveal a novel model for an intestinal bowel disease phenotype that occurs upon combined loss of the DNA repair cofactors ATMIN and NBS1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "abstract" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1366, "text": "Our findings reveal a novel model for an intestinal bowel disease phenotype that occurs upon combined loss of the DNA repair cofactors ATMIN and NBS1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1038, "text": "In contrast, loss of both ATMIN and NBS1 enhanced DNA damage that drove spontaneous peripheral T cell hyperactivation, proliferation as well as excessive production of proinflammatory cytokines and chemokines, leading to a highly inflammatory environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 782, "text": "We show loss of NBS1 led to a developmental block at the double-positive stage of T cell development, as well as reduced TCR\u03b1 recombination, that was unexpectedly neither exacerbated nor alleviated by concomitant loss of ATMIN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26544571", "endSection": "title" } ] }, { "body": "The MMR vaccine protects against what 3 viruses?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7686463", "http://www.ncbi.nlm.nih.gov/pubmed/26265115" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0065828", "o": "http://linkedlifedata.com/resource/umls/label/A18558018" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18558018", "o": "mmr vaccine" } ], "ideal_answer": [ "The MMR vaccine provides immunity to measles, mumps and rubella.", " measles, mumps and rubella (mmr) vaccine ." ], "exact_answer": [ [ "Measles" ], [ "Mumps" ], [ "Rubella" ] ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012411", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012412", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008458", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022542", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009109", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009108", "http://www.disease-ontology.org/api/metadata/DOID:934" ], "type": "list", "id": "58f4b73b70f9fc6f0f000014", "snippets": [ { "offsetInBeginSection": 29, "offsetInEndSection": 71, "text": " measles, mumps and rubella (MMR) vaccine ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26265115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Measles, mumps, rubella (MMR) vaccine is a live vaccine preparation containing attenuated strains of all 3 viruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7686463", "endSection": "abstract" } ] }, { "body": "List cardinal features of the Triple A syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "http://www.ncbi.nlm.nih.gov/pubmed/27411173", "http://www.ncbi.nlm.nih.gov/pubmed/27385299", "http://www.ncbi.nlm.nih.gov/pubmed/16938764", "http://www.ncbi.nlm.nih.gov/pubmed/20200814", "http://www.ncbi.nlm.nih.gov/pubmed/11196451", "http://www.ncbi.nlm.nih.gov/pubmed/12429595", "http://www.ncbi.nlm.nih.gov/pubmed/27698338", "http://www.ncbi.nlm.nih.gov/pubmed/17880786", "http://www.ncbi.nlm.nih.gov/pubmed/15217518", "http://www.ncbi.nlm.nih.gov/pubmed/27555148", "http://www.ncbi.nlm.nih.gov/pubmed/12752575", "http://www.ncbi.nlm.nih.gov/pubmed/22538409", "http://www.ncbi.nlm.nih.gov/pubmed/20687490", "http://www.ncbi.nlm.nih.gov/pubmed/21656342", "http://www.ncbi.nlm.nih.gov/pubmed/26243364" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0326926", "o": "cardinal" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0326926", "o": "http://linkedlifedata.com/resource/umls/label/A18618465" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18618465", "o": "cardinal" } ], "ideal_answer": [ "Triple A syndrome, also known as Allgrove syndrome, is a rare disease, and presents mainly in children. Its cardinal symptoms are achalasia, alacrima, and adrenal insufficiency." ], "exact_answer": [ [ "achalasia" ], [ "alacrima" ], [ "adrenal insufficiency" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050602" ], "type": "list", "id": "5895bfdc7d9090f35300000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "UNLABELLED: Triple A syndrome (alacrima, achalasia, adrenal failure, progressive neurodegenerative disease) is caused by mutations in the AAAS gene which encodes the protein alacrima achalasia adrenal insufficiency neurologic disorder (ALADIN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26243364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Triple A syndrome, also known as Allgrove syndrome, is a rare disease, and presents mainly in children. Its cardinal symptoms are achalasia, alacrima, and adrenocorticotropic hormone (ACTH) insensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27385299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Oesophageal achalasia is well-recognized but relatively rare in children, occasionally appearing as the \"triple A\" syndrome (with adrenal insufficiency and alacrima).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27411173", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 358, "text": "Patients usually display the triad of achalasia, alacrima, and adrenocorticotropin (ACTH) insensitive adrenal insufficiency, though the presentation is inconsistent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27698338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Allgrove (Triple A) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrimia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Triple A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder characterized by three cardinal symptoms: adrenal insufficiency due to ACTH insensitivity, achalasia and alacrima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20200814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Allgrove (Triple A) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrimia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "endSection": "abstract" } ] }, { "body": "Describe the applicability of Basset in the context of deep learning", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27197224" ], "ideal_answer": [ "Basset is an open source package which applies CNNs to learn the functional activity of DNA sequences from genomics data. Basset was trained on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrated greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome." ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069553", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069550" ], "type": "summary", "id": "5891c2e7621ea6ff7e00000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27197224", "endSection": "title" }, { "offsetInBeginSection": 375, "offsetInEndSection": 1287, "text": "We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27197224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27197224", "endSection": "title" } ] }, { "body": "Does the Abelson-related gene (ARG) gene encode for a serine kinase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18411439", "http://www.ncbi.nlm.nih.gov/pubmed/25849507", "http://www.ncbi.nlm.nih.gov/pubmed/15987940", "http://www.ncbi.nlm.nih.gov/pubmed/12220663", "http://www.ncbi.nlm.nih.gov/pubmed/1923513", "http://www.ncbi.nlm.nih.gov/pubmed/23707396", "http://www.ncbi.nlm.nih.gov/pubmed/2649173", "http://www.ncbi.nlm.nih.gov/pubmed/15765532", "http://www.ncbi.nlm.nih.gov/pubmed/18810762", "http://www.ncbi.nlm.nih.gov/pubmed/12821941", "http://www.ncbi.nlm.nih.gov/pubmed/19563810", "http://www.ncbi.nlm.nih.gov/pubmed/9828110", "http://www.ncbi.nlm.nih.gov/pubmed/10590083" ], "ideal_answer": [ "No, the ARG gene encodes for a nonreceptor tyrosine kinase." ], "exact_answer": "no", "concepts": [ "http://www.uniprot.org/uniprot/ABL2_HUMAN", "http://www.uniprot.org/uniprot/ABL2_MOUSE" ], "type": "yesno", "id": "58db94948acda34529000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707396", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The human Arg (Abl2) nonreceptor tyrosine kinase has a role in cytoskeletal rearrangements by its C-terminal F-actin- and microtubule-binding sequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18810762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10590083", "endSection": "title" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1041, "text": " The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10590083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Ultraviolet-A and -B differentially modify the tyrosine-kinase profile of human keratinocytes and induce the expression of Arg+.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18411439", "endSection": "title" }, { "offsetInBeginSection": 434, "offsetInEndSection": 648, "text": "Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18411439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "To investigate the expression profile of protein tyrosine kinases (PTKs) in normal human epidermal keratinocytes (NHEK) in response to UVA and UVB we employed a reversed transcriptase polymerase chain reaction (PCR) approach using degenerate primers derived from the conserved catalytic domain of PTKs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18411439", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 671, "text": "By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10590083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707396", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 646, "text": "Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18411439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "We studied the relationship of direct karyotypes, determined at diagnosis and remission, to Abelson-related tyrosine kinase activity and the cytogenetic features of erythroid and myeloid colonies derived from remission marrow of six children with acute lymphoblastic leukemia (ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2649173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase) family of tyrosine kinases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25849507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707396", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 974, "text": "The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10590083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase) family of tyrosine kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25849507", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 374, "text": "We report that the Abelson (Abl) and Abl-related gene (Arg) nonreceptor tyrosine kinases are required for maintenance of cortical dendrites in the mouse brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15987940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The products of the human ARG gene and the human ABL gene characterize the Abelson family of non-receptor tyrosine protein kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12220663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The products of the human Arg gene and human, mouse, Drosophila, and nematode Abl genes characterize the Abelson family of nonreceptor tyrosine protein kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9828110", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 673, "text": "By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10590083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10590083", "endSection": "title" } ] }, { "body": "What organism causes tularemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26336102", "http://www.ncbi.nlm.nih.gov/pubmed/21607086", "http://www.ncbi.nlm.nih.gov/pubmed/26189939", "http://www.ncbi.nlm.nih.gov/pubmed/18304778", "http://www.ncbi.nlm.nih.gov/pubmed/21687806", "http://www.ncbi.nlm.nih.gov/pubmed/25494920", "http://www.ncbi.nlm.nih.gov/pubmed/22662210", "http://www.ncbi.nlm.nih.gov/pubmed/25847026", "http://www.ncbi.nlm.nih.gov/pubmed/25266682", "http://www.ncbi.nlm.nih.gov/pubmed/20885922", "http://www.ncbi.nlm.nih.gov/pubmed/23473220", "http://www.ncbi.nlm.nih.gov/pubmed/19863554", "http://www.ncbi.nlm.nih.gov/pubmed/24351753" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0041351", "o": "Tularemia" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0041351", "o": "http://linkedlifedata.com/resource/umls/label/A18613230" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18613230", "o": "tularemia" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0041351", "o": "http://linkedlifedata.com/resource/umls/label/A18594521" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18594521", "o": "tularaemia" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0041351", "o": "http://linkedlifedata.com/resource/umls/label/A18668851" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18668851", "o": "tularemias" } ], "ideal_answer": [ "Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. F. tularensis is the causative agent of zoonotic tularemia. ", "Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans.", "Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. ", "francisella tularensis, the agent of tularemia, is a gram-negative coccobacillus primarily pathogen for animals and occasionally for humans." ], "exact_answer": [ "Francisella tularensis" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.disease-ontology.org/api/metadata/DOID:14239", "http://www.disease-ontology.org/api/metadata/DOID:13226", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014406", "http://www.disease-ontology.org/api/metadata/DOID:2122", "http://www.disease-ontology.org/api/metadata/DOID:2123", "http://www.biosemantics.org/jochem#4244019", "http://www.disease-ontology.org/api/metadata/DOID:11990", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=organisms_category" ], "type": "factoid", "id": "58f4b9d470f9fc6f0f000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26189939", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 208, "text": "F. tularensis is the causative agent of zoonotic tularemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26336102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Tularemia is a zoonosis caused by Francisella tularensis that can be transmitted by several ways to human being and cause different clinical manifestations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25847026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Tularemia is a bacterial zoonotic disease that is caused by Francisella tularensis and among the infectious reasons that cause fever of unknown origin (FUO) in children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The bacterium Francisella tularensis causes the vector-borne zoonotic disease tularemia, and may infect a wide range of hosts including invertebrates, mammals and birds", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25266682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Francisella tularensis, the Gram-negative bacterium that causes tularemia, is considered a potential bioterrorism threat due to its low infectivity dose and the high morbidity and mortality from respiratory disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24351753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Francisella tularensis causes disease (tularemia) in a large number of mammals, including man", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25494920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "The tularemia-causing bacterium Francisella tularensis is a facultative intracellular organism with a complex intracellular lifecycle that ensures its survival and proliferation in a variety of mammalian cell types, including professional phagocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21687806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Francisella tularensis is a highly virulent bacterium that causes tularemia, a disease that is often fatal if untreated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18304778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22662210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Tularemia, caused by the bacterium Francisella tularensis, where F.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20885922", "endSection": "abstract" } ] }, { "body": "Is Prochlorococcus the most abundant photosynthetic organism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19549842", "http://www.ncbi.nlm.nih.gov/pubmed/11595938", "http://www.ncbi.nlm.nih.gov/pubmed/25435307", "http://www.ncbi.nlm.nih.gov/pubmed/25977791" ], "ideal_answer": [ "Yes, the marine cyanobacterium Prochlorococcus is the smallest and most abundant photosynthetic organism on Earth." ], "exact_answer": "yes", "type": "yesno", "id": "58ea659c3e8b6dc87c000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "The marine cyanobacterium Prochlorococcus is the smallest and most abundant photosynthetic organism on Earth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25435307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The marine cyanobacterium Prochlorococcus is the numerically dominant photosynthetic organism in the oligotrophic oceans, and a model system in marine microbial ecology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25977791", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The marine cyanobacterium Prochlorococcus is the most abundant photosynthetic organism in oligotrophic regions of the oceans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The oceanic picoplankton Prochlorococcus - probably the most abundant photosynthetic organism on our planet - can grow at great depths where light intensity is very low.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11595938", "endSection": "abstract" } ] }, { "body": "List 3 features of IRVAN syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24221466", "http://www.ncbi.nlm.nih.gov/pubmed/22454754", "http://www.ncbi.nlm.nih.gov/pubmed/15348989", "http://www.ncbi.nlm.nih.gov/pubmed/26922651", "http://www.ncbi.nlm.nih.gov/pubmed/9121757", "http://www.ncbi.nlm.nih.gov/pubmed/25383801", "http://www.ncbi.nlm.nih.gov/pubmed/27239579", "http://www.ncbi.nlm.nih.gov/pubmed/25390402", "http://www.ncbi.nlm.nih.gov/pubmed/27491854", "http://www.ncbi.nlm.nih.gov/pubmed/21563921", "http://www.ncbi.nlm.nih.gov/pubmed/12504719", "http://www.ncbi.nlm.nih.gov/pubmed/25802506", "http://www.ncbi.nlm.nih.gov/pubmed/24269400", "http://www.ncbi.nlm.nih.gov/pubmed/24766157" ], "ideal_answer": [ "Idiopathic retinal vasculitis, aneurysms, and neuroretinitis is coined as IRVAN syndrome." ], "exact_answer": [ [ "Idiopathic retinal vasculitis" ], [ "Aneurysms" ], [ "Neuroretinitis" ] ], "type": "list", "id": "5895dd6a7d9090f35300000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Fluorescein photodiagnosis of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome: A case report and long-term outcome of photocoagulation therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27491854", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a disease characterized by multiple retinal macroaneurysms, neuroretinitis and peripheral capillary non-perfusion, leading to irreversible visual loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27491854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "[Early treatment of idiopathic vasculitis, aneurysms and neuroretinitis (IRVAN). A case report].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24269400", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "CASE REPORT: A 55 year old woman presented with retinal vasculitis, multiple aneurysms, macular exudation and widespread retinal nonperfusion and was diagnosed with IRVAN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24269400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A 7-year-old girl with IRVAN (idiopathic retinal vasculitis, aneurysms, and neuroretinitis) syndrome was monitored for 9 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24766157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Vision loss associated with the idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome most commonly occurs from macular edema or complications related to neovascularization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24221466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "PURPOSE: To report a case of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody (P-ANCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22454754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "PURPOSE: We report our experience in treating 2 patients of idiopathic retinal vasculitis, aneurysm, and neuroretinitis (IRVAN) syndrome with antitumor necrosis factor agent, infliximab, who showed a very favorable response to treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21563921", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 702, "text": "Fluorescein angiography delineated saccular aneurysms of the retinal arteriolar vasculature, and IRVAN syndrome was diagnosed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15348989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "The authors describe the clinical feature of ten patients with a new syndrome characterized by the presence of retinal vasculitis, multiple macroaneurysms, neuro-retinitis, and peripheral capillary nonperfusion.The authors evaluated ten patients identified to have clinical features compatible with the syndrome of idiopathic retinal vasculitis, aneurysms and neuroretinits (IRVAN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9121757", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 383, "text": "The authors evaluated ten patients identified to have clinical features compatible with the syndrome of idiopathic retinal vasculitis, aneurysms and neuroretinits (IRVAN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9121757", "endSection": "abstract" } ] }, { "body": "Which are the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) inhibitors that are FDA approved?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27086681", "http://www.ncbi.nlm.nih.gov/pubmed/26785741", "http://www.ncbi.nlm.nih.gov/pubmed/27533159", "http://www.ncbi.nlm.nih.gov/pubmed/27661220", "http://www.ncbi.nlm.nih.gov/pubmed/27567901", "http://www.ncbi.nlm.nih.gov/pubmed/26345307", "http://www.ncbi.nlm.nih.gov/pubmed/26445204", "http://www.ncbi.nlm.nih.gov/pubmed/26822080", "http://www.ncbi.nlm.nih.gov/pubmed/26798848", "http://www.ncbi.nlm.nih.gov/pubmed/26548330", "http://www.ncbi.nlm.nih.gov/pubmed/26652782", "http://www.ncbi.nlm.nih.gov/pubmed/26886466", "http://www.ncbi.nlm.nih.gov/pubmed/27207595", "http://www.ncbi.nlm.nih.gov/pubmed/26596726", "http://www.ncbi.nlm.nih.gov/pubmed/23889692", "http://www.ncbi.nlm.nih.gov/pubmed/27186592", "http://www.ncbi.nlm.nih.gov/pubmed/26968977" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0243077", "o": "inhibitors" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0243077", "o": "http://linkedlifedata.com/resource/umls/label/A8396238" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8396238", "o": "inhibitors" } ], "ideal_answer": [ "The PCSK9 inhibitors that are FDA approved are:\n1) Alirocumab and \n2) Evolocumab." ], "exact_answer": [ [ "Alirocumab", "Praluent" ], [ "Evolocumab", "Repatha" ] ], "concepts": [ "http://www.uniprot.org/uniprot/PCSK9_MACMU", "http://www.uniprot.org/uniprot/PCSK9_COLGU", "http://www.uniprot.org/uniprot/PCSK9_PONPY", "http://www.uniprot.org/uniprot/PCSK9_CALJA", "http://www.uniprot.org/uniprot/PCSK9_SAGLB", "http://www.uniprot.org/uniprot/PCSK9_PANTR", "http://www.uniprot.org/uniprot/PCSK9_LAGLA", "http://www.uniprot.org/uniprot/PCSK9_MACNE", "http://www.uniprot.org/uniprot/PCSK9_HUMAN", "http://www.uniprot.org/uniprot/PCSK9_ATEGE", "http://www.uniprot.org/uniprot/PCSK9_PANPA", "http://www.uniprot.org/uniprot/PCSK9_PLEMO" ], "type": "list", "id": "58dbb3f18acda34529000019", "snippets": [ { "offsetInBeginSection": 626, "offsetInEndSection": 776, "text": "Inhibition of the PCSK9 protein by monoclonal antibodies results in a dramatic 40%-60% lowering of serum low-density lipoprotein cholesterol (LDL-C). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26822080", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1384, "text": "Alirocumab and evolocumab have been approved by the FDA for the treatment of patients with heterozygous familial hypercholesterolemia and patients with clinical atherosclerotic cardiovascular disease) who do not achieve their LDL-C target on maximal tolerated statin treatment and dietary modification. In addition, evolocumab has been approved by the FDA for homozygous familial hypercholesterolemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26822080", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 382, "text": "LDL cholesterol (LDLC) lowering has been revolutionized by PCSK9 inhibitors, Alirocumab (Praluent) and Evolocumab (Repatha), approved as adjuncts to maximally tolerated cholesterol lowering therapy in heterozygous (HeFH) or homozygous (HoFH) familial hypercholesterolemia, and/or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26968977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "A new class of lipid-lowering drugs, inhibitors of PCSK9 has been generating impressive clinical trial data over the last several years, and alirocumab (Praluent) has become the first to be approved by the US FDA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26785741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The second FDA-approved PCSK9 inhibitor evolocumab (Repatha) appears to be similar in efficacy and safety to alirocumab (Praluent), but no comparative studies are available. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26445204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, have recently been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27086681", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 944, "text": "Newer agents for LDL cholesterol reduction include the cholesterol ester transfer protein inhibitors, the microsomal triglyceride transfer protein inhibitor lomitapide, the apolipoprotein B antisense oligonucleotide mipomersen and several molecules that inhibit or interfere with proprotein convertase subtilisin/kexin 9 (PCSK9).Among the various PCSK9 inhibitors, human data are available for monoclonal antibodies against PCSK9 of which the two most advanced are alirocumab (SAR236553/REGN727) and AMG 145", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23889692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "The 2 or 4\u2011week subcutaneous therapy with the recently approved antibodies alirocumab and evolocumab for inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) reduces low-density lipoprotein cholesterol (LDL-C) in addition to statins and ezetimibe by 50-60\u2009%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27207595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 487, "text": "In 2015 the U.S. Food and Drug Administration approved the first two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab (Praluent\u00ae; Sanofi/ Regeneron) and evolocumab (Repatha\u00ae; Amgen), for use in patients with heterozygous and homozygous familial hypercholesterolemia and for patients intolerant of statins or those with a major risk of cardiovascular disease (CVD) but unable to lower their LDL cholesterol (LDL-C) to optimal levels with statins and ezetimibe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27186592", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1135, "text": "Very recent clinical trials have proven overwhelmingly the effectiveness and safety of PCSK9 inhibitors for lowering LDL-C. Both alirocumab and evolocumab have now been approved by the US FDA and there are some initial favorable outcomes data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26596726", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 487, "text": "Food and Drug Administration approved the first two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab (Praluent\u00ae; Sanofi/ Regeneron) and evolocumab (Repatha\u00ae; Amgen), for use in patients with heterozygous and homozygous familial hypercholesterolemia and for patients intolerant of statins or those with a major risk of cardiovascular disease (CVD) but unable to lower their LDL cholesterol (LDL-C) to optimal levels with statins and ezetimibe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27186592", "endSection": "abstract" } ] }, { "body": "Is dupilumab an antibody targeting the IL-1 receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26440137", "http://www.ncbi.nlm.nih.gov/pubmed/27130691", "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "http://www.ncbi.nlm.nih.gov/pubmed/27497276", "http://www.ncbi.nlm.nih.gov/pubmed/26308331" ], "ideal_answer": [ "No, Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor \u03b1 subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways." ], "exact_answer": "no", "type": "yesno", "id": "58df5efbc784871774000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Atopic dermatitis (AD) is characterized by type 2 helper T (Th2) cell-driven inflammation. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor \u03b1 subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598956", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 818, "text": "Dupilumab, a humanized monoclonal antibody to the interteukin-4R is the first antibody (i.e. 'biological') with published efficacy shown in controlled prospective studies in atopic dermatitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26308331", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 248, "text": "Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690741", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1337, "text": "Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor \u03b1-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27497276", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 187, "text": " Dupilumab, a fully human anti-interleukin-4 receptor \u03b1 monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27130691", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1169, "text": "Dupilumab was also introduced as a possible treatment for patients with severe pemphigus. It can directly inhibit IL-4 by targeting IL-4 \u03b1-chain receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26440137", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 217, "text": "We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "endSection": "abstract" } ] }, { "body": "List active ingredients of the Stribild polypill.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24338165", "http://www.ncbi.nlm.nih.gov/pubmed/25553805", "http://www.ncbi.nlm.nih.gov/pubmed/27225853", "http://www.ncbi.nlm.nih.gov/pubmed/26286337", "http://www.ncbi.nlm.nih.gov/pubmed/23136357", "http://www.ncbi.nlm.nih.gov/pubmed/26045359", "http://www.ncbi.nlm.nih.gov/pubmed/26679246" ], "ideal_answer": [ "Active ingredients of Stribild are elvitegravir, cobicistat, emtricitabine and tenofovir. It is used for treatment of HIV infection." ], "exact_answer": [ [ "elvitegravir" ], [ "cobicistat" ], [ "emtricitabine" ], [ "tenofovir" ] ], "type": "list", "id": "5895dfc97d9090f353000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "PURPOSE: The purpose of this study is to assess postmarketing safety and tolerability of Stribild (elvitegravir [EVG]/cobicistat [COBI]/tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27225853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "INTRODUCTION: Co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir (EVG/COBI/FTC/TDF or Stribild\u2122) is the latest antiretroviral tablet approved in the EU. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25553805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "BACKGROUND: Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF; Stribild(\u00ae)) is a guideline-recommended regimen for HIV treatment-na\u00efve patients and a switch option for virologically suppressed patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26045359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "BACKGROUND: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF; Stribild(\u00ae)) is a recommended integrase inhibitor-based regimen in treatment guidelines from the US Department of Health and Human Services and the British HIV Association. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26286337", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen (Stribild\u00ae): a review of its use in the management of HIV-1 infection in adults.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24338165", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 533, "text": "A new single-tablet, fixed-dose formulation consisting of elvitegravir, an HIV-1 integrase strand transfer inhibitor (INSTI); cobicistat, a pharmacokinetic enhancer; emtricitabine, a nucleoside reverse transcriptase inhibitor; and tenofovir disoproxil fumarate (tenofovir DF), a nucleotide reverse transcriptase inhibitor (elvitegravir/cobicistat/emtricitabine/tenofovir DF 150 mg/150 mg/200 mg/300 mg; Stribild\u00ae) is available in some countries for the once-daily treatment of HIV-1 infection in antiretroviral therapy-na\u00efve adults. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24338165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "To review the clinical trials, pharmacologic characteristics, safety, and efficacy of the elvitegravir/cobicistat/emtricitabine/tenofovir single tablet formulation (Stribild).Literature searches were performed in MEDLINE (1948-September 2012) and PubMed (1966-September 2012) using the search terms GS-9137, elvitegravir, GS 9350, cobicistat, quad pill, Stribild, and integrase inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23136357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 419, "text": "To evaluate dolutegravir and elvitegravir/cobicistat pharmacokinetics in HIV-negative volunteers up to 10 days after drug cessation.Healthy volunteers received 50 mg of dolutegravir once-daily for 10 days, then underwent a 9 day wash-out period, and then received elvitegravir/cobicistat as part of Stribild(\u00ae) (245 mg of tenofovir, 200 mg of emtricitabine, 150 mg of elvitegravir and 150 mg of cobicistat) for 10 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679246", "endSection": "abstract" } ] }, { "body": "List clinical features of the IMAGe syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25517553", "http://www.ncbi.nlm.nih.gov/pubmed/25861374", "http://www.ncbi.nlm.nih.gov/pubmed/16835919", "http://www.ncbi.nlm.nih.gov/pubmed/25258553", "http://www.ncbi.nlm.nih.gov/pubmed/22634751", "http://www.ncbi.nlm.nih.gov/pubmed/25541901", "http://www.ncbi.nlm.nih.gov/pubmed/24313804", "http://www.ncbi.nlm.nih.gov/pubmed/24617583", "http://www.ncbi.nlm.nih.gov/pubmed/14760276", "http://www.ncbi.nlm.nih.gov/pubmed/21108398" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0683325", "o": "http://linkedlifedata.com/resource/umls/label/A18567231" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0683325", "o": "clinical aspects" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0683325", "o": "http://linkedlifedata.com/resource/umls/label/A18697112" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18697112", "o": "clinical aspects" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0683325", "o": "http://linkedlifedata.com/resource/umls/label/A1810832" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1810832", "o": "clinical aspects" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0683325", "o": "http://linkedlifedata.com/resource/umls/label/A18585749" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18585749", "o": "aspects clinical" } ], "ideal_answer": [ "Clinical features of IMAGe syndrome include intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities. It is s caused by gain-of-function mutations of maternally expressed gene CDKN1C on chromosome 11p15.5." ], "exact_answer": [ [ "intra-uterine growth restriction" ], [ "metaphyseal dysplasia" ], [ "adrenal hypoplasia congenita" ], [ "genital abnormalities" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050885" ], "type": "list", "id": "5895e4637d9090f353000012", "snippets": [ { "offsetInBeginSection": 171, "offsetInEndSection": 461, "text": "Recently, our group described gain-of-function mutations in the PCNA-binding site of CDKN1C that result in an undergrowth syndrome called IMAGe Syndrome (Intrauterine Growth Restriction, Metaphyseal dysplasia, Adrenal hypoplasia, and Genital anomalies), with life-threatening consequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25861374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "IMAGe syndrome is an exceedingly rare condition first described in 1999. Components of the syndrome are intrauterine growth retardation (IUGR), metaphyseal dysplasia, congenital adrenal hypoplasia and genital anomalies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25541901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "OBJECTIVE: Arboleda et al. have recently shown that IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome is caused by gain-of-function mutations of maternally expressed gene CDKN1C on chromosome 11p15.5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24313804", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 493, "text": "Intriguing is that CDKN1C gain-of-function variations were recently found in patients with IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258553", "endSection": "abstract" } ] }, { "body": "Which gene mutations are predictive of response to anti-TNF therapy in Rheumatoid Arthritis patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26440629", "http://www.ncbi.nlm.nih.gov/pubmed/22044414", "http://www.ncbi.nlm.nih.gov/pubmed/25848939" ], "ideal_answer": [ "\u039cutations in TLR5 and TLR1 genes contribute to differential response to anti-TNF treatment in RA. Variation at FCGR2A and functionally related genes such as DHX32 and RGS12 is also associated with the response to anti-TNF therapy in rheumatoid arthritis." ], "exact_answer": [ [ "TLR5" ], [ "TLR1" ], [ "FCGR2A" ], [ "DHX32" ], [ "RGS12" ] ], "type": "list", "id": "58e7a1393e8b6dc87c00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26440629", "endSection": "title" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1682, "text": "Six of twenty successfully genotyped polymorphisms were nominally associated with EULAR treatment response. Three of these were in weak to moderate linkage disequilibrium with polymorphisms previously reported associated with anti-TNF treatment response. TLR5(rs5744174) variant allele carriers (odds ratio(OR) = 1.7(1.1-2.5),p = 0.010,q = 0.46) and TLR1(rs4833095) homozygous variant carriers (OR = 2.8(1.1-7.4),p = 0.037,q = 0.46) had higher odds for a positive treatment response. NLRP3(rs10754558) variant allele carriers (odds ratio(OR) = 0.6(0.4-1.0),p = 0.045,q = 0.46) were more likely to have a negative treatment response. The association in TLR5(rs5744174) remained significant after correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4-16.3),p = 0.0002,q = 0.024). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26440629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Variation at FCGR2A and functionally related genes is associated with the response to anti-TNF therapy in rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848939", "endSection": "title" }, { "offsetInBeginSection": 306, "offsetInEndSection": 511, "text": "We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848939", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 642, "text": "A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848939", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 969, "text": " Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848939", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1459, "text": "We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848939", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1684, "text": "We found a significant association between the genetic variation at DHX32 (rs12356233, corrected P=0.019) and a nominally significant association between RGS12 and the response to adalimumab (rs4690093, uncorrected P=0.040).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848939", "endSection": "abstract" }, { "offsetInBeginSection": 1685, "offsetInEndSection": 1857, "text": "In the anti-CCP positive group of patients, we also found a nominally significant association between RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25848939", "endSection": "abstract" } ] }, { "body": "Which method is used for prediction of novel microRNA genes in cancer-associated genomic regions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19324892" ], "ideal_answer": [ "SSCprofiler is a computational tool utilizing a probabilistic method based on Profile Hidden Markov Models to predict novel miRNA precursors. Via the simultaneous integration of biological features such as sequence, structure and conservation, SSCprofiler achieves a performance accuracy of 88.95% sensitivity and 84.16% specificity on a large set of human miRNA genes. The trained classifier is used to identify novel miRNA gene candidates located within cancer-associated genomic regions and rank the resulting predictions using expression information from a full genome tiling array. SSCprofiler is freely available as a web service at http://www.imbb.forth.gr/SSCprofiler.html." ], "exact_answer": [ "SSCprofiler" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ], "type": "factoid", "id": "5895f18ce370baff39000001", "snippets": [ { "offsetInBeginSection": 425, "offsetInEndSection": 1429, "text": " In this work we present a new computational tool (SSCprofiler) utilizing a probabilistic method based on Profile Hidden Markov Models to predict novel miRNA precursors. Via the simultaneous integration of biological features such as sequence, structure and conservation, SSCprofiler achieves a performance accuracy of 88.95% sensitivity and 84.16% specificity on a large set of human miRNA genes. The trained classifier is used to identify novel miRNA gene candidates located within cancer-associated genomic regions and rank the resulting predictions using expression information from a full genome tiling array. Finally, four of the top scoring predictions are verified experimentally using northern blot analysis. Our work combines both analytical and experimental techniques to show that SSCprofiler is a highly accurate tool which can be used to identify novel miRNA gene candidates in the human genome. SSCprofiler is freely available as a web service at http://www.imbb.forth.gr/SSCprofiler.html.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324892", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 594, "text": "In this work we present a new computational tool (SSCprofiler) utilizing a probabilistic method based on Profile Hidden Markov Models to predict novel miRNA precursors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324892", "endSection": "abstract" }, { "offsetInBeginSection": 1143, "offsetInEndSection": 1334, "text": "Our work combines both analytical and experimental techniques to show that SSCprofiler is a highly accurate tool which can be used to identify novel miRNA gene candidates in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324892", "endSection": "abstract" } ] }, { "body": "Does the histone chaperone ASF1 interact with histones H1/H2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22291963", "http://www.ncbi.nlm.nih.gov/pubmed/21329878", "http://www.ncbi.nlm.nih.gov/pubmed/18096807", "http://www.ncbi.nlm.nih.gov/pubmed/20347990", "http://www.ncbi.nlm.nih.gov/pubmed/17690098", "http://www.ncbi.nlm.nih.gov/pubmed/19172748", "http://www.ncbi.nlm.nih.gov/pubmed/16229457", "http://www.ncbi.nlm.nih.gov/pubmed/21895891", "http://www.ncbi.nlm.nih.gov/pubmed/25618846", "http://www.ncbi.nlm.nih.gov/pubmed/23184661", "http://www.ncbi.nlm.nih.gov/pubmed/20048053", "http://www.ncbi.nlm.nih.gov/pubmed/26522166", "http://www.ncbi.nlm.nih.gov/pubmed/17166288", "http://www.ncbi.nlm.nih.gov/pubmed/20227376", "http://www.ncbi.nlm.nih.gov/pubmed/18334479", "http://www.ncbi.nlm.nih.gov/pubmed/17107956", "http://www.ncbi.nlm.nih.gov/pubmed/27036862", "http://www.ncbi.nlm.nih.gov/pubmed/16627621", "http://www.ncbi.nlm.nih.gov/pubmed/23569117", "http://www.ncbi.nlm.nih.gov/pubmed/17293877", "http://www.ncbi.nlm.nih.gov/pubmed/25781956", "http://www.ncbi.nlm.nih.gov/pubmed/22323608", "http://www.ncbi.nlm.nih.gov/pubmed/22463819", "http://www.ncbi.nlm.nih.gov/pubmed/17081967", "http://www.ncbi.nlm.nih.gov/pubmed/24824343", "http://www.ncbi.nlm.nih.gov/pubmed/22106264", "http://www.ncbi.nlm.nih.gov/pubmed/19403047", "http://www.ncbi.nlm.nih.gov/pubmed/17576589", "http://www.ncbi.nlm.nih.gov/pubmed/19782028", "http://www.ncbi.nlm.nih.gov/pubmed/24209620" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C2752385", "o": "histone chaperone" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2752385", "o": "http://linkedlifedata.com/resource/umls/label/A17474145" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17474145", "o": "histone chaperone" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2752385", "o": "http://linkedlifedata.com/resource/umls/label/A17470574" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17470574", "o": "histone chaperone" } ], "ideal_answer": [ "No, the histone chaperone ASF1 interacts with histones H3/H4." ], "exact_answer": "no", "concepts": [ "http://www.uniprot.org/uniprot/ASF1_CANGA", "http://www.uniprot.org/uniprot/ASF1_CRYNJ", "http://www.uniprot.org/uniprot/ASF1_ASPFU", "http://www.uniprot.org/uniprot/ASF1_ENCCU", "http://www.uniprot.org/uniprot/ASF1_ASHGO", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056488", "http://www.uniprot.org/uniprot/ASF1_YARLI", "http://www.uniprot.org/uniprot/ASF1_COCIM", "http://www.uniprot.org/uniprot/ASF1_DROME", "http://www.uniprot.org/uniprot/ASF1_CHICK", "http://www.uniprot.org/uniprot/ASF1_CRYNB", "http://www.uniprot.org/uniprot/ASF1_USTMA", "http://www.uniprot.org/uniprot/ASF1_CANAL", "http://www.uniprot.org/uniprot/ASF1_DEBHA", "http://www.uniprot.org/uniprot/ASF1_KLULA" ], "type": "yesno", "id": "58dcbb8c8acda34529000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The central histone H3/H4 chaperone Asf1 comprises a highly conserved globular core and a divergent C-terminal tail. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The histone H3-H4 chaperone Asf1 is involved in chromatin assembly (or disassembly), histone exchange, regulation of transcription, and chromatin silencing in several organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22291963", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1051, "text": "An ASF1-EGFP fusion protein localizes to the nucleus. By tandem-affinity purification/mass spectrometry as well as yeast two-hybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22463819", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 671, "text": " This inhibition requires Asf1 binding to H3-H4 and Rtt109 KAT activity, but not tail acetylation of H3-H4 or K56 acetylation of H3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22106264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Asf1 is a conserved histone H3/H4 chaperone that can assemble and disassemble nucleosomes and promote histone acetylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048053", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 674, "text": "Here we characterize further interactions between budding yeast (Saccharomyces cerevisiae) Asf1 and Set2 using assays of intragenic transcription, H3/H4 posttranslational modification, coding region cross-linking of Asf1 and Set2, and cooccurrence of Asf1 and Set2 in protein complexes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048053", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1120, "text": "Consistent with this possibility, we show that Asf1 stimulates Set2 occupancy of the coding region of a highly transcribed gene by a mechanism that depends on Asf1 binding to H3/H4. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20048053", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 431, "text": "Drosophila histones H3 and H4 can also be produced as a soluble (H3H4)(2) heterotetrameric complex if they are co-expressed with the histone chaperone Asf1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20347990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17293877", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 274, "text": "Newly synthesized histones H3-H4 first bind histone chaperone Asf1 and are then transferred to other chaperones for nucleosome assembly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24209620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16627621", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 243, "text": "Antisilencing function 1 (ASF1) is a major histone H3-H4 chaperone that deposits histones H3 and H4 onto DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16229457", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 344, "text": "Rtt109, a recently discovered histone acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification associated with newly synthesized histones", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19172748", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "In this issue of Cell, English et al. present the first crystal structure of a histone chaperone (Asf1) bound to histones (the H3/H4 heterodimer)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17081967", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1050, "text": "By tandem-affinity purification/mass spectrometry as well as yeast two-hybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22463819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17107956", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1258, "text": "Analysis of a panel of Asf1 mutations that modulate the ability of Asf1 to bind to histones H3/H4 demonstrates that the histone binding activity of Asf1 is required for the acetylation of Lys-9 and Lys-56 on newly synthesized H3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17107956", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 975, "text": "Thus Rad53 competes with histones H3-H4 and cochaperones HirA/CAF-I for binding to Asf1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22323608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17293877", "endSection": "title" }, { "offsetInBeginSection": 261, "offsetInEndSection": 396, "text": "Currently, the best-characterized chaperone-histone interaction is that between the ubiquitous chaperone Asf1 and a dimer of H3 and H4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21329878", "endSection": "abstract" } ] }, { "body": "Is Hepatic mesenchymal hamartoma usually a malignant tumor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23164031", "http://www.ncbi.nlm.nih.gov/pubmed/16833000", "http://www.ncbi.nlm.nih.gov/pubmed/19365132", "http://www.ncbi.nlm.nih.gov/pubmed/18022426", "http://www.ncbi.nlm.nih.gov/pubmed/23351454", "http://www.ncbi.nlm.nih.gov/pubmed/17493912", "http://www.ncbi.nlm.nih.gov/pubmed/16544232", "http://www.ncbi.nlm.nih.gov/pubmed/2267227", "http://www.ncbi.nlm.nih.gov/pubmed/15785401", "http://www.ncbi.nlm.nih.gov/pubmed/27833980", "http://www.ncbi.nlm.nih.gov/pubmed/8942272", "http://www.ncbi.nlm.nih.gov/pubmed/17713740", "http://www.ncbi.nlm.nih.gov/pubmed/18071280", "http://www.ncbi.nlm.nih.gov/pubmed/20954316", "http://www.ncbi.nlm.nih.gov/pubmed/22935827" ], "ideal_answer": [ "Mesenchymal hamartoma of the liver (MHL) is an uncommon benign hepatic tumor typically affecting children under 2 years of age.", "Mesenchymal hamartoma of the liver (MHL) is a benign and rare hepatic lesion, ", "mesenchymal hamartoma of the liver (mhl) is an uncommon benign hepatic tumor typically affecting children under 2 years of age." ], "exact_answer": "no", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006223", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006222", "http://www.disease-ontology.org/api/metadata/DOID:3467", "http://www.disease-ontology.org/api/metadata/DOID:6108", "http://www.disease-ontology.org/api/metadata/DOID:3462" ], "type": "yesno", "id": "58f3cd1470f9fc6f0f00000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Mesenchymal hamartoma of the liver (MHL) is a benign and rare hepatic lesion, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27833980", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Mesenchymal hamartoma of the liver (MHL) is an uncommon benign hepatic tumor typically affecting children under 2 years of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22935827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "This review on the pathology of hepatic tumors in childhood, from a personal series of 245 tumors, focuses on incidence, management, description of frequent tumors such as hepatoblastoma, fibrolamellar carcinoma, and undifferentiated sarcoma for malignant tumors, focal nodular hyperplasia, hepatocellular adenoma, and mesenchymal hamartoma for benign tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15785401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Mesenchymal hamartoma of the liver is a rare benign liver tumor in children, usually arising from the right liver lobe and represents about 5 to 6% of all primary hepatic tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23351454", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 216, "text": "Hepatic mesenchymal hamartoma (HMH) is the second most common benign hepatic tumor in children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23164031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Hepatic mesenchymal hamartoma is a rare benign tumor in children, and infantile hepatic hemangioendothelioma is also a rare liver neoplasm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17493912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "This review on the pathology of hepatic tumors in childhood, from a personal series of 245 tumors, focuses on incidence, management, description of frequent tumors such as hepatoblastoma, fibrolamellar carcinoma, and undifferentiated sarcoma for malignant tumors, focal nodular hyperplasia, hepatocellular adenoma, and mesenchymal hamartoma for benign tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15785401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Mesenchymal hamartoma is a rare and benign tumor.. Representing 5 to 8 % of childrens hepatic tumors, it is rarely described in adults", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16833000", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 319, "text": "We report a case of hepatic mesenchymal hamartoma, a rare benign tumour, in a 10-month-old infant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8942272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Hepatic mesenchymal hamartoma is a rare benign tumour in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16544232", "endSection": "abstract" }, { "offsetInBeginSection": 4673, "offsetInEndSection": 4780, "text": "Mesenchymal hamartoma is a benign lesion best treated by surgical resection, which usually results in cure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18022426", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 811, "text": "Hepatic mesenchymal hamartoma are rare benign tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19365132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Hepatic mesenchymal hamartoma is a rare benign tumor in children, and infantile hepatic hemangioendothelioma is also a rare liver neoplasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17493912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Mesenchymal hamartoma is an uncommon benign hepatic tumor arising from the mesenchyme of the portal triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20954316", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 124, "text": "esenchymal hamartoma of the liver (MHL) is an uncommon benign tumor found primarily in children younger than 2 years of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17713740", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 234, "text": " case of a prenatally recognized hepatic mesenchymal hamartoma is presented and the literature reviewed. These tumors are benign and usually present in early infancy with symptoms that are related to the mass effect on adjacent organ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2267227", "endSection": "abstract" } ] }, { "body": "List clinical features of EEM syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25707507", "http://www.ncbi.nlm.nih.gov/pubmed/10420194", "http://www.ncbi.nlm.nih.gov/pubmed/11424132", "http://www.ncbi.nlm.nih.gov/pubmed/22140374", "http://www.ncbi.nlm.nih.gov/pubmed/15805154", "http://www.ncbi.nlm.nih.gov/pubmed/2628819", "http://www.ncbi.nlm.nih.gov/pubmed/16970031", "http://www.ncbi.nlm.nih.gov/pubmed/18199584", "http://www.ncbi.nlm.nih.gov/pubmed/6302256" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0683325", "o": "http://linkedlifedata.com/resource/umls/label/A18567231" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0683325", "o": "http://linkedlifedata.com/resource/umls/label/A18585749" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18585749", "o": "aspects clinical" } ], "ideal_answer": [ "EEM syndrome is characterized by ectodermal dysplasia, ectrodactyly and macular dystrophy." ], "exact_answer": [ [ "ectodermal dysplasia" ], [ "ectrodactyly" ], [ "macular dystrophy" ] ], "type": "list", "id": "5895e9977d9090f353000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Hypotrichosis with juvenile macular dystrophy (HJMD) and ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM) are both caused by mutations in the CDH3 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22140374", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 567, "text": "Loss-of-function mutations in CDH3, which encodes P-cadherin, result in two allelic autosomal recessive disorders: hypotrichosis with juvenile macular dystrophy (HJMD) and ectodermal dysplasia, ectrodactyly, and macular dystrophy (EEM) syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25707507", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 348, "text": "Recently, mutations in the P-cadherin gene (CDH3) have been shown to cause two inherited diseases in humans: hypotrichosis with juvenile macular dystrophy (HJMD) and ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18199584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "EEM syndrome is a rare condition characterised by ectodermal dysplasia, ectrodactyly and macular dystrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16970031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "BACKGROUND: EEM syndrome is the rare association of ectodermal dysplasia, ectrodactyly, and macular dystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805154", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM syndrome) in siblings.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11424132", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Association of ectodermal dysplasia, ectrodactyly, and macular dystrophy: the EEM syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6302256", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Association of ectodermal dysplasia, ectrodactyly and macular dystrophy: EEM syndrome (case report).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2628819", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "EEM syndrome is the rare association of ectodermal dysplasia, ectrodactyly, and macular dystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "We report a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy (the EEM syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11424132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM syndrome) in siblings.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11424132", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15805154", "endSection": "title" } ] }, { "body": "How many times is CLAST faster than BLAST?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25495907" ], "ideal_answer": [ "was capable of identifying sequence similarities ~80.8 times faster than blast and 9.6 times faster than blat . ", "CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT", "CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT. ", "clast was capable of identifying sequence similarities ~80.8 times faster than blast and 9.6 times faster than blat.", "CLAST is capable of identifying sequence similarities ~80.8 times faster than BLAST" ], "exact_answer": [ "80.8 times", "80.8" ], "type": "factoid", "id": "58f6295a70f9fc6f0f000019", "snippets": [ { "offsetInBeginSection": 920, "offsetInEndSection": 1035, "text": "CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495907", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1011, "text": "First, CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495907", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1014, "text": "First, CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495907", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1015, "text": "First, CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495907", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1016, "text": "First, CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495907", "endSection": "abstract" } ] }, { "body": "Which are the most common methods for circular RNA detection from RNASeq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27167008", "http://www.ncbi.nlm.nih.gov/pubmed/26657634" ], "ideal_answer": [ "The main algorithms are circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice.", "Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. ", "Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance.", "CircRNAs are novel members of the non-coding RNA family. Several pipelines have been developed to specifically identify these non-linear reads and consequently predict the landscape of circRNAs based on deep sequencing datasets. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance.", ", use common rnaseq datasets to scrutinize and compare the output from five different algorithms; circrna_finder , find_circ , circexplorer , ciri , and mapsplice and evaluate the levels of bona fide and false positive circrnas based on rnase r resistance. . ", "here, we use common rnaseq datasets to scrutinize and compare the output from five different algorithms; circrna.finder, find.circ, circexplorer, ciri, and mapsplice and evaluate the levels of bona fide and false positive circrnas based on rnase r resistance." ], "exact_answer": [ [ "circRNA_finder" ], [ "find_circ" ], [ "CIRCexplorer" ], [ "CIRI" ], [ "MapSplice" ] ], "type": "list", "id": "58e640573e8b6dc87c000003", "snippets": [ { "offsetInBeginSection": 492, "offsetInEndSection": 751, "text": "Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26657634", "endSection": "abstract" } ] }, { "body": "From which cell type is leptin secreted?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12242022", "http://www.ncbi.nlm.nih.gov/pubmed/11606782", "http://www.ncbi.nlm.nih.gov/pubmed/23376443", "http://www.ncbi.nlm.nih.gov/pubmed/22692856", "http://www.ncbi.nlm.nih.gov/pubmed/10443698", "http://www.ncbi.nlm.nih.gov/pubmed/12448771", "http://www.ncbi.nlm.nih.gov/pubmed/17639037", "http://www.ncbi.nlm.nih.gov/pubmed/17132702", "http://www.ncbi.nlm.nih.gov/pubmed/11979056", "http://www.ncbi.nlm.nih.gov/pubmed/11824506", "http://www.ncbi.nlm.nih.gov/pubmed/17149693", "http://www.ncbi.nlm.nih.gov/pubmed/26732322", "http://www.ncbi.nlm.nih.gov/pubmed/23016759", "http://www.ncbi.nlm.nih.gov/pubmed/24975960", "http://www.ncbi.nlm.nih.gov/pubmed/21371463", "http://www.ncbi.nlm.nih.gov/pubmed/23503941" ], "ideal_answer": [ "leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode.", " Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland.", " Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland. Lipolysis (stimulated by beta-adrenergic agents) and leptin secretion by adipocytes are down-regulated by neurons in coculture, effects apparently mediated by neuropeptide Y (NPY)", "Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland. Lipolysis (stimulated by beta-adrenergic agents) and leptin secretion by adipocytes are down-regulated by neurons in coculture, effects apparently mediated by neuropeptide Y (NPY). Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands. ", "Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands.", "Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode.", "Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands. Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode.", "Leptin is a 16 kDa protein that exerts important effects on the regulation of food intake and energy expenditure by interacting with the leptin receptor in the brain and in many other tissues. Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland.", "Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands. Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland." ], "exact_answer": [ "adipocytes" ], "type": "factoid", "id": "58ee0dd5eda5a57672000013", "snippets": [ { "offsetInBeginSection": 192, "offsetInEndSection": 387, "text": " Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11824506", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 775, "text": "Lipolysis (stimulated by beta-adrenergic agents) and leptin secretion by adipocytes are down-regulated by neurons in coculture, effects apparently mediated by neuropeptide Y (NPY)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11606782", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 309, "text": "Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12448771", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1613, "text": "Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12448771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Leptin, a circulating hormone secreted mainly from adipose tissues, possesses protective effects on many cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21371463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Leptin, the adipocyte-secreted hormone that regulates weight, is known to link lipid metabolism with inflammation in various cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24975960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Leptin, a 16-kDa protein that is mainly secreted by adipocytes, plays a protective role in many cell types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Do the adipocytokines, leptin and adiponectin affect the granulosa cell expression of anti-Mullerian hormone (AMH) and its receptor (AMHR-II)?Leptin suppresses AMH mRNA levels in human luteinized granulosa cells through the JAK2/STAT3 pathway, while adiponectin has no such effect.AMH is one of the most reliable markers of ovarian reserve", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23503941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Leptin, the adipocyte-secreted hormone, exerts its main function as regulator of food intake and energy expenditure through central effects at the hypothalamic level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12242022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Adipokines are a group of fat-secreted hormones and cytokines, including leptin and adiponectin, with important functions in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17132702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Leptin, an adipose-secreted hormone, links metabolism and immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23016759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26732322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Adipokines (leptin, adiponectin, and hepatocyte growth factor (HGF)) secreted from adipose tissue have come to be recognized for their contribution to the mechanisms by which obesity and related metabolic disorders influence breast cancer risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17639037", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 916, "text": "These results show that there is a distinct female-type and male-type leptin pulsatility pattern and each is amenable to augmentation by gonadal steroids either involving mechanisms that impart leptin pulsatility patterns directly at the level of adipocytes and/or at hypothalamic target sites..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11979056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Leptin is a circulating hormone secreted by adipose and a few other tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10443698", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 927, "text": "Cyclin D1 is expressed exclusively in luminal keratin 8 immunoreactive tumor cells and is dependent on the adipose secreted hormone leptin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22692856", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1017, "text": "In gastric cells leptin follows a rapid regulated secretion pathway whereas adipocytes secrete leptin in a constitutive slow fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17149693", "endSection": "abstract" } ] }, { "body": "Which tool is used for the identification of recurrent variants in noncoding regions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26304545" ], "ideal_answer": [ "LARVA is an integrative framework for large-scale analysis of recurrent variants in noncoding annotations. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a \u03b2-binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers." ], "exact_answer": [ "LARVA" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000071184", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012045" ], "type": "factoid", "id": "589635dd78275d0c4a000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "LARVA: an integrative framework for large-scale analysis of recurrent variants in noncoding annotations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26304545", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1428, "text": "In cancer research, background models for mutation rates have been extensively calibrated in coding regions, leading to the identification of many driver genes, recurrently mutated more than expected. Noncoding regions are also associated with disease; however, background models for them have not been investigated in as much detail. This is partially due to limited noncoding functional annotation. Also, great mutation heterogeneity and potential correlations between neighboring sites give rise to substantial overdispersion in mutation count, resulting in problematic background rate estimation. Here, we address these issues with a new computational framework called LARVA. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a \u03b2-binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. We demonstrate LARVA's effectiveness on 760 whole-genome tumor sequences, showing that it identifies well-known noncoding drivers, such as mutations in the TERT promoter. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers. We make LARVA available as a software tool and release our highly mutated annotations as an online resource (larva.gersteinlab.org).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26304545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "LARVA: an integrative framework for large-scale analysis of recurrent variants in noncoding annotations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26304545", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "LARVA: an integrative framework for large-scale analysis of recurrent variants in noncoding annotations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26304545", "endSection": "title" } ] }, { "body": "What body parts are also known as phalanges?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19700363", "http://www.ncbi.nlm.nih.gov/pubmed/2187446", "http://www.ncbi.nlm.nih.gov/pubmed/16965880", "http://www.ncbi.nlm.nih.gov/pubmed/22250842", "http://www.ncbi.nlm.nih.gov/pubmed/24486016", "http://www.ncbi.nlm.nih.gov/pubmed/7366585" ], "ideal_answer": [ "The anatomical structure of each finger is comprised of four phalanges (distal, middle, proximal, and metacarpal phalange). Toes are also known as phalages" ], "exact_answer": [ "bones of the digits, fingers or toes" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050278", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050277" ], "type": "factoid", "id": "58f3c62970f9fc6f0f00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Metacarpal and phalangeal fractures of the long fingers a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24486016", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 857, "text": " The anatomical structure of each finger is comprised of four phalanges (distal, middle, proximal, and metacarpal phalange).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19700363", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 488, "text": "arious features of the toes, humps in the toe line, phalange marks, flatfoot condition, pits, cracks, corns, etc., were studied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965880", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 722, "text": "802), in which physical injuries are listed, ranging from loss of single phalanges, differentiated between thumb, forefinger, small finger, and the other fingers, to death, is compared with modern grades of disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2187446", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 742, "text": "They featured a prominent unpaired femur besides paired tibiotarsi, tarsometatarsi and species-specific phalanges of the toes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22250842", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 495, "text": "The bone structure is rarefied at the distal metaphyses of the metacarpals and the proximal metaphyses of the finger basal phalanges.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7366585", "endSection": "abstract" } ] }, { "body": "Are selenium supplements recommended for prostate cancer prevention?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26957512", "http://www.ncbi.nlm.nih.gov/pubmed/25990689", "http://www.ncbi.nlm.nih.gov/pubmed/25854337", "http://www.ncbi.nlm.nih.gov/pubmed/25505227" ], "ideal_answer": [ "No. The SELECT study failed to show any significant risk reduction for prostate cancers ascribable to selenium and vitamin E supplementations." ], "exact_answer": "no", "type": "yesno", "id": "58f0b40d70f9fc6f0f000008", "snippets": [ { "offsetInBeginSection": 1431, "offsetInEndSection": 1794, "text": "Our meta-analysis in prospective studies demonstrated a significant inverse association between selenium status and CVD risk within a narrow selenium range and a null effect of selenium supplementation on CVD was observed in RCTs. These findings indicate the importance of considering selenium status, dose and safety in health assessment and future study design.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25990689", "endSection": "abstract" }, { "offsetInBeginSection": 1763, "offsetInEndSection": 1995, "text": "Selenium supplementation of 140 or more \u03bcg/day after diagnosis of nonmetastatic prostate cancer may increase risk of prostate cancer mortality. Caution is warranted regarding usage of such supplements among men with prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25505227", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 729, "text": "The SELECT study failed to show any significant risk reduction for prostate cancers ascribable to selenium and vitamin E supplementations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25854337", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 1016, "text": "Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26957512", "endSection": "abstract" } ] }, { "body": "Which disease is treated with lucinactant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15813666", "http://www.ncbi.nlm.nih.gov/pubmed/18822258", "http://www.ncbi.nlm.nih.gov/pubmed/16896079", "http://www.ncbi.nlm.nih.gov/pubmed/23473590", "http://www.ncbi.nlm.nih.gov/pubmed/16452346", "http://www.ncbi.nlm.nih.gov/pubmed/23032799", "http://www.ncbi.nlm.nih.gov/pubmed/23118645", "http://www.ncbi.nlm.nih.gov/pubmed/15805380", "http://www.ncbi.nlm.nih.gov/pubmed/22821059", "http://www.ncbi.nlm.nih.gov/pubmed/22859930", "http://www.ncbi.nlm.nih.gov/pubmed/17533176", "http://www.ncbi.nlm.nih.gov/pubmed/15805381", "http://www.ncbi.nlm.nih.gov/pubmed/22791092" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1609686", "o": "lucinactant" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1609686", "o": "http://linkedlifedata.com/resource/umls/label/A20633234" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20633234", "o": "lucinactant" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1609686", "o": "http://linkedlifedata.com/resource/umls/label/A8604556" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8604556", "o": "lucinactant" } ], "ideal_answer": [ "Lucinactant us used for the prevention of respiratory distress syndrome in premature infants." ], "exact_answer": [ "respiratory distress syndrome" ], "concepts": [ "http://www.biosemantics.org/jochem#4002240", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.disease-ontology.org/api/metadata/DOID:4" ], "type": "factoid", "id": "5896271178275d0c4a000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Lucinactant for the prevention of respiratory distress syndrome in premature infants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473590", "endSection": "title" }, { "offsetInBeginSection": 174, "offsetInEndSection": 795, "text": "Lucinactant is a synthetic surfactant containing sinapultide, a bioengineered peptide mimic of surfactant-associated protein B. A meta-analysis of clinical trials demonstrates that lucinactant is as effective as animal-derived surfactants in preventing RDS in premature neonates, and in vitro studies suggest it is more resistant to oxidative and protein-induced inactivation. Its synthetic origin confers lower infection and inflammation risks as well other potential benefits, which may make lucinactant an advantageous alternative to its animal-derived counterparts, which are presently the standard treatment for RDS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473590", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 383, "text": "We evaluated whether intratracheal lucinactant, a synthetic, peptide-containing surfactant, was safe and well-tolerated in infants with acute hypoxemic respiratory failure, and assessed its effects on clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791092", "endSection": "abstract" }, { "offsetInBeginSection": 2555, "offsetInEndSection": 2747, "text": "An improvement in oxygenation and a significantly reduced requirement for retreatment suggests that lucinactant might improve lung function in infants with acute hypoxemic respiratory failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22791092", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1527, "text": "CONCLUSION: These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Lucinactant for the treatment of respiratory distress syndrome in neonates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23032799", "endSection": "title" }, { "offsetInBeginSection": 714, "offsetInEndSection": 977, "text": "The clinical trials that have been performed, although underpowered, may indicate that lucinactant is superior to phospholipid synthetic surfactant preparations and at least as effective as animal-derived surfactants in reducing morbidity and mortality from RDS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23032799", "endSection": "abstract" } ] }, { "body": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25989903", "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "http://www.ncbi.nlm.nih.gov/pubmed/25210768", "http://www.ncbi.nlm.nih.gov/pubmed/19854134", "http://www.ncbi.nlm.nih.gov/pubmed/25680078", "http://www.ncbi.nlm.nih.gov/pubmed/24106327", "http://www.ncbi.nlm.nih.gov/pubmed/21826286", "http://www.ncbi.nlm.nih.gov/pubmed/27492286", "http://www.ncbi.nlm.nih.gov/pubmed/21878619", "http://www.ncbi.nlm.nih.gov/pubmed/19169244" ], "ideal_answer": [ "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. ", "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. ", "The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and RNA-processing complexes, coupling RNA processing to the RNA degradation machinery.", "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3 These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene.", "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). ", "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3", "Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome and Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complexes. The termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity." ], "exact_answer": [ [ "Rrp6" ], [ "Nrd1" ], [ "Nab3" ], [ "TRAMP complex", "Trf4/5-Air1/2-Mtr4 polyadenylation" ], [ "Sen1" ] ], "type": "list", "id": "58adca6d9ef3c34033000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "title" }, { "offsetInBeginSection": 118, "offsetInEndSection": 374, "text": "These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1057, "text": " These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 234, "text": "Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25210768", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1450, "text": "Lack of TRAMP activity stabilises \u223c 1600 CUTs in meiotic cells, which occupy 40% of the binding capacity of the nuclear cap binding complex (CBC). CBC mutants display defects in the formation of meiotic double strand breaks (DSBs), and we see similar defects in TRAMP mutants, suggesting that a key function of the nuclear exosome is to prevent saturation of the CBC complex by CUTs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25210768", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 895, "text": "We find that TRAMP mutants produce high levels of CUTs during meiosis that are undetectable in wild-type cells, showing that the nuclear exosome remains functional for CUT degradation, and we further report that the meiotic exosome complex contains Rrp6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25210768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680078", "endSection": "title" }, { "offsetInBeginSection": 239, "offsetInEndSection": 515, "text": "Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680078", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 819, "text": "Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680078", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 439, "text": "Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome cofactor that recruits the exosome to degrade RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21878619", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 652, "text": " The MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25989903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The eukaryotic exosome exoribonuclease Rrp6 forms a complex with Rrp47 that functions in nuclear RNA quality control mechanisms, the degradation of cryptic unstable transcripts (CUTs), and in the 3 end maturation of stable RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24106327", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 795, "text": "Nrd1 and Nab3 colocalize to regions of the genome expressing antisense CUTs, and these transcripts require yeast nuclear exosome and TRAMP components for degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Genome-wide studies have identified abundant small, noncoding RNAs, including small nuclear RNAs, small nucleolar RNAs (snoRNAs), cryptic unstable transcripts (CUTs), and upstream regulatory RNAs (uRNAs), that are transcribed by RNA polymerase II (pol II) and terminated by an Nrd1-dependent pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19854134", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 797, "text": "Nrd1 and Nab3 colocalize to regions of the genome expressing antisense CUTs, and these transcripts require yeast nuclear exosome and TRAMP components for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 775, "text": "Here, by examining the overlap of stable (SUTs, stable unannotated transcripts) and unstable (CUTs, cryptic unstable transcripts) transcripts with protein-coding genes, we show that the predicted Nrd1 and Nab3-binding site sequences occur at differing frequencies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27492286", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 510, "text": "Examples are the consensus binding site sequences of the RNA-binding proteins Nrd1 and Nab3 that target non-coding transcripts for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27492286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "title" }, { "offsetInBeginSection": 187, "offsetInEndSection": 350, "text": "Some are designated Cryptic Unstable Transcripts (CUTs) because they are terminated by the Nrd1-Nab3-Sen1 pathway and then rapidly degraded by the nuclear exosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21826286", "endSection": "abstract" } ] }, { "body": "Is there any involvement of L1 retrotransposition in the Rett syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22159035", "http://www.ncbi.nlm.nih.gov/pubmed/24389010", "http://www.ncbi.nlm.nih.gov/pubmed/23057747", "http://www.ncbi.nlm.nih.gov/pubmed/21085180" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1514925", "o": "http://linkedlifedata.com/resource/umls/label/A11585268" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11585268", "o": "retrotransposon transposition" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0035372", "o": "http://linkedlifedata.com/resource/umls/label/A18593781" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18593781", "o": "rett syndrome" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1514925", "o": "transposition, RNA-mediated" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1514925", "o": "http://linkedlifedata.com/resource/umls/label/A11610160" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11610160", "o": "retrotransposition" } ], "ideal_answer": [ "Yes. Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015518", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020084", "http://www.disease-ontology.org/api/metadata/DOID:1206" ], "type": "yesno", "id": "58965a4178275d0c4a00000e", "snippets": [ { "offsetInBeginSection": 1585, "offsetInEndSection": 2128, "text": "Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition. Our data demonstrate that L1 retrotransposition can be controlled in a tissue-specific manner and that disease-related genetic mutations can influence the frequency of neuronal L1 retrotransposition. Our findings add a new level of complexity to the molecular events that can lead to neurological disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21085180", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 903, "text": "Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23057747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24389010", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 594, "text": "In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22159035", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 896, "text": "Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23057747", "endSection": "abstract" }, { "offsetInBeginSection": 1576, "offsetInEndSection": 1811, "text": "Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21085180", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 592, "text": "In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22159035", "endSection": "abstract" }, { "offsetInBeginSection": 1585, "offsetInEndSection": 1819, "text": "Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21085180", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 901, "text": "Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23057747", "endSection": "abstract" }, { "offsetInBeginSection": 1585, "offsetInEndSection": 1820, "text": "Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21085180", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 902, "text": "Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23057747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24389010", "endSection": "abstract" } ] }, { "body": "Is Downs syndrome associated with decreased risk of leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19332933", "http://www.ncbi.nlm.nih.gov/pubmed/25332567", "http://www.ncbi.nlm.nih.gov/pubmed/16321814", "http://www.ncbi.nlm.nih.gov/pubmed/2955886" ], "ideal_answer": [ "No, multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population." ], "exact_answer": "no", "type": "yesno", "id": "58f3d85170f9fc6f0f00000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "The association of Down's syndrome and leukemia has been documented for over 50 years. Multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2955886", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 564, "text": "We present a case of congenital acute myeloid leukemia manifesting from the very first day of birth. Diagnosis of acute myeloid leukemia was suspected by the presence of blasts in the peripheral blood smear and was confirmed on bone marrow by flowcytometry. Karyotyping revealed Trisomy 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332567", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1040, "text": "Juvenile myelomonocytic leukemia (JMML) and a solitary cases of acute myeloid leukemia (AML) in Downs syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16321814", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 712, "text": "This was thus confirmed to be a case with transient leukemia with Downs syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19332933", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by ixazomib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27119237", "http://www.ncbi.nlm.nih.gov/pubmed/26667773", "http://www.ncbi.nlm.nih.gov/pubmed/27121262", "http://www.ncbi.nlm.nih.gov/pubmed/26846321", "http://www.ncbi.nlm.nih.gov/pubmed/25377318", "http://www.ncbi.nlm.nih.gov/pubmed/26988986", "http://www.ncbi.nlm.nih.gov/pubmed/25919767", "http://www.ncbi.nlm.nih.gov/pubmed/26558304", "http://www.ncbi.nlm.nih.gov/pubmed/25234165", "http://www.ncbi.nlm.nih.gov/pubmed/26709701", "http://www.ncbi.nlm.nih.gov/pubmed/26138345", "http://www.ncbi.nlm.nih.gov/pubmed/26588946", "http://www.ncbi.nlm.nih.gov/pubmed/26658418", "http://www.ncbi.nlm.nih.gov/pubmed/27783987", "http://www.ncbi.nlm.nih.gov/pubmed/27325500", "http://www.ncbi.nlm.nih.gov/pubmed/26141494", "http://www.ncbi.nlm.nih.gov/pubmed/23514361", "http://www.ncbi.nlm.nih.gov/pubmed/26872892", "http://www.ncbi.nlm.nih.gov/pubmed/27261328", "http://www.ncbi.nlm.nih.gov/pubmed/26337806", "http://www.ncbi.nlm.nih.gov/pubmed/25456369", "http://www.ncbi.nlm.nih.gov/pubmed/27702799", "http://www.ncbi.nlm.nih.gov/pubmed/26811670", "http://www.ncbi.nlm.nih.gov/pubmed/26634271", "http://www.ncbi.nlm.nih.gov/pubmed/27259216", "http://www.ncbi.nlm.nih.gov/pubmed/25302026", "http://www.ncbi.nlm.nih.gov/pubmed/26947893" ], "ideal_answer": [ "Ixazomib is proteasome inhibitor. It is used for treatment of multiple myeloma." ], "exact_answer": [ "proteasome" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ], "type": "factoid", "id": "589630f378275d0c4a000007", "snippets": [ { "offsetInBeginSection": 144, "offsetInEndSection": 492, "text": "Over the past decade, MM therapy is significantly improved by the introduction of novel therapeutics such as immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), monoclonal antibodies (daratumumab and elotuzumab), histone deacetylase (HDAC) inhibitors (Panobinostat).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27261328", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 516, "text": "Due to the largely incurable nature of multiple myeloma, the development of newer agents is ongoing and includes new oral PIs (ixazomib), immunotherapies (e.g., CD38- or SLAMF7-targeted antibodies), and small molecules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26558304", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 394, "text": "Ixazomib (MLN9708-MLN2238), the second-generation proteasome inhibitor, selectivity and potency were similar to that of bortezomib, is currently being investigated in phase I studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26667773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26658418", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 551, "text": "Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26588946", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 893, "text": "Since the introduction of bortezomib in 2003, several next-generation proteasome inhibitors have also been used clinically, including carfilzomib, oprozomib, ixazomib, and delanzomib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26947893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "AIM: The aim of the present study was to characterize the pharmacokinetics of the oral proteasome inhibitor, ixazomib, in patients with solid tumours and moderate or severe hepatic impairment, to provide posology recommendations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27121262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Pharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27121262", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Ixazomib is the first oral, proteasome inhibitor to reach phase III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26141494", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 350, "text": "MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27783987", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "This population pharmacokinetic analysis of the investigational oral proteasome inhibitor ixazomib assessed the feasibility of switching from body surface area (BSA)-based to fixed dosing, and the impact of baseline covariates on ixazomib pharmacokinetics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25377318", "endSection": "abstract" } ] }, { "body": "Does PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds with HDL-receptor (HDL-R)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27284008", "http://www.ncbi.nlm.nih.gov/pubmed/26040332", "http://www.ncbi.nlm.nih.gov/pubmed/20529551", "http://www.ncbi.nlm.nih.gov/pubmed/23675525", "http://www.ncbi.nlm.nih.gov/pubmed/26318398", "http://www.ncbi.nlm.nih.gov/pubmed/23400816", "http://www.ncbi.nlm.nih.gov/pubmed/25649668", "http://www.ncbi.nlm.nih.gov/pubmed/26256967", "http://www.ncbi.nlm.nih.gov/pubmed/22683370", "http://www.ncbi.nlm.nih.gov/pubmed/23690465", "http://www.ncbi.nlm.nih.gov/pubmed/24164109", "http://www.ncbi.nlm.nih.gov/pubmed/21692990", "http://www.ncbi.nlm.nih.gov/pubmed/23974119", "http://www.ncbi.nlm.nih.gov/pubmed/21122852", "http://www.ncbi.nlm.nih.gov/pubmed/23261172", "http://www.ncbi.nlm.nih.gov/pubmed/25679794", "http://www.ncbi.nlm.nih.gov/pubmed/26495026", "http://www.ncbi.nlm.nih.gov/pubmed/24094767", "http://www.ncbi.nlm.nih.gov/pubmed/23106476", "http://www.ncbi.nlm.nih.gov/pubmed/21497351", "http://www.ncbi.nlm.nih.gov/pubmed/22580899", "http://www.ncbi.nlm.nih.gov/pubmed/17702855", "http://www.ncbi.nlm.nih.gov/pubmed/20716520", "http://www.ncbi.nlm.nih.gov/pubmed/26056005", "http://www.ncbi.nlm.nih.gov/pubmed/23141813", "http://www.ncbi.nlm.nih.gov/pubmed/22300679", "http://www.ncbi.nlm.nih.gov/pubmed/25463543", "http://www.ncbi.nlm.nih.gov/pubmed/24685817", "http://www.ncbi.nlm.nih.gov/pubmed/25905719", "http://www.ncbi.nlm.nih.gov/pubmed/26548330", "http://www.ncbi.nlm.nih.gov/pubmed/24603306", "http://www.ncbi.nlm.nih.gov/pubmed/22907332", "http://www.ncbi.nlm.nih.gov/pubmed/26088304", "http://www.ncbi.nlm.nih.gov/pubmed/19828345", "http://www.ncbi.nlm.nih.gov/pubmed/26364362", "http://www.ncbi.nlm.nih.gov/pubmed/18436719", "http://www.ncbi.nlm.nih.gov/pubmed/26023080", "http://www.ncbi.nlm.nih.gov/pubmed/17493938", "http://www.ncbi.nlm.nih.gov/pubmed/22176652", "http://www.ncbi.nlm.nih.gov/pubmed/25744035", "http://www.ncbi.nlm.nih.gov/pubmed/25070550", "http://www.ncbi.nlm.nih.gov/pubmed/24144304", "http://www.ncbi.nlm.nih.gov/pubmed/25971287", "http://www.ncbi.nlm.nih.gov/pubmed/26195630" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1426592", "o": "PCSK9" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1426592", "o": "http://linkedlifedata.com/resource/umls/label/A20814698" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A20814698", "o": "proprotein convertase subtilisin/kexin type 9" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2611277", "o": "http://linkedlifedata.com/resource/umls/label/A19343187" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0062151", "o": "http://linkedlifedata.com/resource/umls/label/A8395721" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8395721", "o": "high density lipoprotein receptors" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0062151", "o": "http://linkedlifedata.com/resource/umls/label/A16773852" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16773852", "o": "high density lipoprotein receptors" } ], "ideal_answer": [ "No, Proprotein Convertase Subtilisin Kexin 9 (PCSK9) binds with LDL-receptor (LDL-R) causing its degradation in the lysosome with the result of LDL-C accumulating in the blood." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:1990666", "http://www.uniprot.org/uniprot/PCSK9_SAIBB", "http://www.uniprot.org/uniprot/PCSK9_MACMU", "http://www.uniprot.org/uniprot/PCSK9_COLGU", "http://www.uniprot.org/uniprot/PCSK9_CALJA", "http://www.uniprot.org/uniprot/PCSK9_SAGLB", "http://www.uniprot.org/uniprot/PCSK9_PONPY", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043484", "http://www.uniprot.org/uniprot/PCSK9_PANTR", "http://www.uniprot.org/uniprot/PCSK9_RAT", "http://www.uniprot.org/uniprot/PCSK9_LAGLA", "http://www.uniprot.org/uniprot/PCSK9_MACNE", "http://www.uniprot.org/uniprot/PCSK9_HUMAN", "http://www.uniprot.org/uniprot/PCSK9_ATEGE", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000071449", "http://www.uniprot.org/uniprot/PCSK9_PANPA", "http://www.uniprot.org/uniprot/PCSK9_PLEMO" ], "type": "yesno", "id": "58db9aa28acda34529000018", "snippets": [ { "offsetInBeginSection": 532, "offsetInEndSection": 747, "text": "Recently it was revealed that the secreted Proprotein Convertase Subtilisin Kexin 9 (PCSK9) binds with LDL-receptor (LDL-R) causing its degradation in the lysosome with the result of LDL-C accumulating in the blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25679794", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1296, "text": "The major goal of this study is to identify peptide/s from the catalytic domain of hPCSK9 that can block the binding of hPCSK9 and LDL-R and therefore can reduce LDL-R degradation leading to the clearance of LDL-C from the plasma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25679794", "endSection": "abstract" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1324, "text": "In vitro administration of SRT3025 to cultured AML12 hepatocytes attenuated Pcsk9 secretion and its binding to Ldlr, thereby reducing Pcsk9-mediated Ldlr degradation and increasing Ldlr expression and LDL uptake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24603306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9), which involves in low-density lipoprotein cholesterol (LDL-C) metabolism by interacting with the LDL receptor, is considered as a potent therapeutic target for treating hypercholesterolemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26056005", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1030, "text": "Taken together, these results suggested that the IgG1-PA4 can be served as a potential candidate for the treatment of hypercholesterolemia by inhibiting PCSK9-mediated degradation of cell surface LDLRs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26056005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor, escorting it to\u00a0its destruction in the lysosome and thereby preventing the recirculation of the low-density lipoprotein receptor to the hepatocyte cell surface. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088304", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 447, "text": "However, statins have low efficiency because they also increase PCSK9 which targets LDLR for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26318398", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 316, "text": "Inhibition of the enzyme PCSK9 (proprotein convertase subtilisin/kexin type 9), which is involved in depletion of the LDL-receptor, is a new pharmacologic approach. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26364362", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 510, "text": "Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26495026", "endSection": "abstract" }, { "offsetInBeginSection": 1656, "offsetInEndSection": 1837, "text": "Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26495026", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 376, "text": "We report here the development of sdAbs targeting human PCSK9 (proprotein convertase subtilisin/kexin type 9) as an alternative to anti-PCSK9 mAbs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27284008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) protein plays an important role in LDL cholesterol (LDL-C) metabolism, due to its role in the degradation of the LDL receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24164109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24094767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400816", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds to the epidermal growth factor-like-A domain of the low density lipoprotein receptor (LDLR) and mediates LDLR degradation in liver", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400816", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 191, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23141813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9), which binds the low-density lipoprotein receptor and targets it for degradation, has emerged as an important regulator of serum cholesterol levels and cardiovascular disease risk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26023080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLR) at the cell surface and disrupts the normal recycling of the LDLR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20716520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the hepatic low-density lipoprotein receptor (LDL-R) and is therefore a prominent therapeutic target for reducing LDL-cholesterol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25744035", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 862, "text": "In the present study we scanned the related gene of a clinically diagnosed autosomal genetic hypercholesterolemia family for the possible mutations and established eukaryotic expression vector of mutation of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene with gene recombination technique to investigate the contributions of the variation on low density lipoprotein receptor (LDL-R) metabolism and function alternation.Mutation detection was conducted for LDL-R, apolipoprotein B(100) (apoB(100)) and PCSK9 gene with nucleotide sequencing in a Chinese FH family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20529551", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 304, "text": "Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22300679", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 323, "text": "The proprotein convertase subtilisin-kexin type 9 (PCSK9) pathway plays a key role in lipoprotein metabolism by promoting LDL-receptor degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261172", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 237, "text": "Proprotein convertase subtilisin-kexin type 9 (PCSK9) plays a key role in LDL receptor processing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21122852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18436719", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 413, "text": "Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25463543", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 299, "text": "Low-density lipoprotein (LDL) metabolism is governed by proprotein convertase subtilisin-kexin type 9 (PCSK9), which down-regulates LDL receptor expression, resulting in higher LDL cholesterol (LDL-C).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23106476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene regulates cholesterol homoeostasis by accelerating low-density lipoprotein receptor (LDLR) degradation resulting in the decreased catabolism of low-density lipoprotein (LDL) leading to hypercholesterolaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25649668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400816", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds to the epidermal growth factor-like-A domain of the low density lipoprotein receptor (LDLR) and mediates LDLR degradation in liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL-cholesterol receptor homeostasis and emerges as a therapeutic target in the prevention of cardiovascular (CV) disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24685817", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 392, "text": "The present study was conducted to investigate the role of plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels, a regulator of LDL-receptor expression, in the occurrence of diabetic dyslipidemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21497351", "endSection": "abstract" } ] }, { "body": "Hy's law measures failure for what organ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24203912", "http://www.ncbi.nlm.nih.gov/pubmed/26116527", "http://www.ncbi.nlm.nih.gov/pubmed/23874514", "http://www.ncbi.nlm.nih.gov/pubmed/22928730", "http://www.ncbi.nlm.nih.gov/pubmed/24704526", "http://www.ncbi.nlm.nih.gov/pubmed/26159259", "http://www.ncbi.nlm.nih.gov/pubmed/23300062", "http://www.ncbi.nlm.nih.gov/pubmed/26122767", "http://www.ncbi.nlm.nih.gov/pubmed/25683797" ], "ideal_answer": [ "Hy's law correlates enzyme elevations with liver injury ad subsequent failure." ], "exact_answer": [ "liver" ], "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065290", "http://www.disease-ontology.org/api/metadata/DOID:2044", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056486", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056487", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008111", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017114", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058625" ], "type": "factoid", "id": "58f4b25e70f9fc6f0f000011", "snippets": [ { "offsetInBeginSection": 169, "offsetInEndSection": 420, "text": " Hy's Law of drug-induced hepatocellular jaundice causing a case-fatality rate or need for transplant of 10% or higher has been validated in several large national registries, including the ongoing, prospective U.S. Drug-Induced Liver Injury Network. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26116527", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 556, "text": "Enzyme elevations alone may not be harmful, but if caused by a drug and followed by jaundice (called 'Hy's law') there is a high possibility of serious DILI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26159259", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1211, "text": "No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23874514", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 717, "text": "We compared its performance with that of Hy's Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample.We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Risk of Acute Liver Failure in Patients With Drug-Induced Liver Injury: Evaluation of Hy's Law and a New Prognostic Model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122767", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24704526", "endSection": "abstract" }, { "offsetInBeginSection": 46, "offsetInEndSection": 116, "text": "Hy's law is a method used to identify drug-induced liver injury (DILI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25683797", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 180, "text": "Potential severe liver injury is identified in clinical trials by ALT>3\u2009\u00d7\u2009upper limits of normal (ULN) and total bilirubin>2\u2009\u00d7\u2009ULN, and termed 'Hy's Law' by the US FDA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22928730", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 327, "text": "Severe liver injury is identified by the liver chemistry threshold of alanine aminotransferase (ALT)>3\u00d7 upper limit of normal (ULN) and bilirubin>2\u00d7 ULN, termed Hy's law by the Food and Drug Administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300062", "endSection": "abstract" } ] }, { "body": "Is apremilast effective for psoriatic arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26220911", "http://www.ncbi.nlm.nih.gov/pubmed/25633241", "http://www.ncbi.nlm.nih.gov/pubmed/27272887", "http://www.ncbi.nlm.nih.gov/pubmed/26644232", "http://www.ncbi.nlm.nih.gov/pubmed/27022911", "http://www.ncbi.nlm.nih.gov/pubmed/26806620", "http://www.ncbi.nlm.nih.gov/pubmed/26923915", "http://www.ncbi.nlm.nih.gov/pubmed/27486641", "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "http://www.ncbi.nlm.nih.gov/pubmed/27747762", "http://www.ncbi.nlm.nih.gov/pubmed/27836567", "http://www.ncbi.nlm.nih.gov/pubmed/25973439", "http://www.ncbi.nlm.nih.gov/pubmed/23134988", "http://www.ncbi.nlm.nih.gov/pubmed/22257911", "http://www.ncbi.nlm.nih.gov/pubmed/27307707", "http://www.ncbi.nlm.nih.gov/pubmed/27168275", "http://www.ncbi.nlm.nih.gov/pubmed/25827658", "http://www.ncbi.nlm.nih.gov/pubmed/23569359", "http://www.ncbi.nlm.nih.gov/pubmed/23580094", "http://www.ncbi.nlm.nih.gov/pubmed/26783350", "http://www.ncbi.nlm.nih.gov/pubmed/27538241", "http://www.ncbi.nlm.nih.gov/pubmed/26660203", "http://www.ncbi.nlm.nih.gov/pubmed/24797159", "http://www.ncbi.nlm.nih.gov/pubmed/26807876", "http://www.ncbi.nlm.nih.gov/pubmed/26503917", "http://www.ncbi.nlm.nih.gov/pubmed/26792812" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C1678805", "o": "APREMILAST" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1678805", "o": "http://linkedlifedata.com/resource/umls/label/A15589751" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A15589751", "o": "apremilast" } ], "ideal_answer": [ "Yes, apremilast, an oral phosphodiesterase 4 inhibitor, is effective for psoriatic arthritis." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015535", "http://www.disease-ontology.org/api/metadata/DOID:9008" ], "type": "yesno", "id": "5896e22078275d0c4a000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26792812", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "OBJECTIVE: To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26792812", "endSection": "abstract" }, { "offsetInBeginSection": 1638, "offsetInEndSection": 1835, "text": "CONCLUSIONS: Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52\u2005weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26792812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Apremilast: A Novel Drug for Treatment of Psoriasis and Psoriatic Arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26783350", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "OBJECTIVE: To review the pharmacology, efficacy, and safety of apremilast and determine its role relative to other agents in the treatment of psoriasis and psoriatic arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26783350", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1495, "text": "CONCLUSIONS: Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26783350", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 269, "text": " In particular, apremilast has been recently approved for the treatment of psoriasis and psoriatic arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26806620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Apremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27538241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of apremilast was invited to submit evidence for its clinical and cost effectiveness for the treatment of active psoriatic arthritis (PsA) for whom disease-modifying anti-rheumatic drugs (DMARDs) have been inadequately effective, not tolerated or contraindicated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27272887", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 331, "text": "Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1095, "text": "In patients with psoriatic arthritis, there are no clinical trials comparing apremilast with TNF alpha antagonists, and no interpretable trials of apremilast after failure of a TNF alpha antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27486641", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 497, "text": "Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1816, "text": "No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed.Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 583, "text": "Apremilast is a novel oral PDE4 enzyme inhibitor capable of blocking leukocyte production of IL-12, IL-23, TNF-a, INF- with subsequent suppression of Th1 and Th17-mediated immune responses, and proven clinical efficacy for psoriasis as well as rheumatoid and psoriatic arthritis.Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) showed a significant (P<0.05) decrease after 85 days of treatment with apremilast 20 mg twice daily in 8 patients with active discoid lupus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23134988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "The purpose of this study is to give an overview of the new treatments approved by the U.S. Food and Drug Administration (FDA) for use in psoriatic arthritis (PsA).FDA has approved three new drugs for PsA: Certolizumab-pegol: a PEGylated Fc-free tumour necrosis factor inhibitor (TNFi); ustekinumab: an anti interleukin (IL)-12 and IL-23 mAb; and apremilast and oral phosphodiesterase 4 inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25633241", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1403, "text": "In all trials, the drug had an acceptable safety profile, with the most common adverse effects of diarrhea, nausea, and headache.Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26783350", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 597, "text": "Apremilast is a well-tolerated and effective phosphodiesterase type 4 inhibitor that is indicated for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27307707", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 498, "text": "Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 961, "text": "Newer drugs in the treatment armamentarium that have shown efficacy for both psoriasis and psoriatic arthritis consist of the anti-IL-17 agent, secukinumab, and a phosphodiesterase-4 inhibitor, apremilast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "To review the pharmacology, efficacy, and safety of apremilast and determine its role relative to other agents in the treatment of psoriasis and psoriatic arthritis.A PubMed search (1946 to December 2015) using the terms apremilast and CC-10004 was conducted to identify relevant articles.In vitro or in vivo evaluations of apremilast published in the English language were eligible for inclusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26783350", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1101, "text": "In patients with psoriatic arthritis, there are no clinical trials comparing apremilast with TNF alpha antagonists, and no interpretable trials of apremilast after failure of a TNF alpha antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27486641", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1817, "text": "No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed.Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 581, "text": "Apremilast is a novel oral PDE4 enzyme inhibitor capable of blocking leukocyte production of IL-12, IL-23, TNF-a, INF- with subsequent suppression of Th1 and Th17-mediated immune responses, and proven clinical efficacy for psoriasis as well as rheumatoid and psoriatic arthritis.Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) showed a significant (P<0.05) decrease after 85 days of treatment with apremilast 20 mg twice daily in 8 patients with active discoid lupus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23134988", "endSection": "abstract" }, { "offsetInBeginSection": 1700, "offsetInEndSection": 1817, "text": "Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1407, "text": "Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26783350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic arthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical trial program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25973439", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 332, "text": "Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24595547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Apremilast: A Review in Psoriasis and Psoriatic Arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26220911", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Drug safety evaluation of apremilast for treating psoriatic arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827658", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Apremilast for the treatment of psoriatic arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503917", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Apremilast mechanism of action and application to psoriasis and psoriatic arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22257911", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Apremilast: A Phosphodiesterase 4 Inhibitor for the Treatment of Psoriatic Arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27747762", "endSection": "title" } ] }, { "body": "Is there any role of TBR1 in autism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24441682", "http://www.ncbi.nlm.nih.gov/pubmed/26578866", "http://www.ncbi.nlm.nih.gov/pubmed/27325115", "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "http://www.ncbi.nlm.nih.gov/pubmed/25309323", "http://www.ncbi.nlm.nih.gov/pubmed/23431145", "http://www.ncbi.nlm.nih.gov/pubmed/25232744" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0004352", "o": "http://linkedlifedata.com/resource/umls/label/A18645844" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18645844", "o": "autistic disorders" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0004352", "o": "Autism" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0004352", "o": "http://linkedlifedata.com/resource/umls/label/A0474209" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0474209", "o": "autism" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0004352", "o": "http://linkedlifedata.com/resource/umls/label/A18571407" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18571407", "o": "autistic disorder" } ], "ideal_answer": [ "Yes. Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including T-Brain-1 (TBR1), a master regulator of cortical development. T-brain-1 (TBR1) is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1 (-\u2215-) mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala, and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000067877", "http://www.uniprot.org/uniprot/TBR1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:12849", "http://www.disease-ontology.org/api/metadata/DOID:0060042", "http://www.disease-ontology.org/api/metadata/DOID:0060041", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321", "http://www.uniprot.org/uniprot/TBR1_HUMAN" ], "type": "yesno", "id": "58965ed478275d0c4a000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "TBR1 regulates autism risk genes in the developing neocortex", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27325115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1160, "text": "Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation. Of the nine ASD genes examined, seven were misexpressed in the cortices of Tbr1 knockout mice, including six with increased expression in the deep cortical layers. ASD genes with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of LoF mutations in a reference human population and among Icelanders. We then leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27325115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "T-Brain-1--A Potential Master Regulator in Autism Spectrum Disorders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "T-Brain-1 (TBR1), a causative gene in autism spectrum disorders (ASDs), encodes a brain-specific T-box transcription factor. It is therefore possible that TBR1 controls the expression of other autism risk factors. The downstream genes of TBR1 have been identified using microarray and promoter analyses. In this study, we annotated individual genes downstream of TBR1 and investigated any associations with ASDs through extensive literature searches. Of 124 TBR1 target genes, 23 were reported to be associated with ASDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1513, "text": "Among these 24 genes, four transcription factors Auts2, Nfia, Nr4a2, and Sox5 were found, suggesting that TBR1 controls a transcriptional cascade relevant to autism pathogenesis. A further five of the 24 genes (Cd44, Cdh8, Cntn6, Gpc6, and Ntng1) encode membrane proteins that regulate cell adhesion and axonal outgrowth. These genes likely contribute to the role of TBR1 in regulation of neuronal migration and axonal extension. Besides, decreases in Grin2b expression and increases in Gad1 expression imply that neuronal activity may be aberrant in Tbr1 deficient mice. These analyses provide direction for future experiments to reveal the pathogenic mechanism of autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "The activity-regulated gene expression of transcription factors is required for neural plasticity and function in response to neuronal stimulation. T-brain-1 (TBR1), a critical neuron-specific transcription factor for forebrain development, has been recognized as a high-confidence risk gene for autism spectrum disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309323", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 212, "text": "Disruptive mutations in the TBR1 gene have been repeatedly identified in patients with autism spectrum disorders (ASDs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24441682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Next-generation sequencing recently revealed that recurrent disruptive mutations in a few genes may account for 1% of sporadic autism cases. Coupling these novel genetic data to empirical assays of protein function can illuminate crucial molecular networks. Here we demonstrate the power of the approach, performing the first functional analyses of TBR1 variants identified in sporadic autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25232744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 657, "text": "T-brain-1 (TBR1) is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1 (-\u2215-) mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala, and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1. Recently, recurrent de novo disruptive mutations in the TBR1 gene have been found in patients with autism spectrum disorders (ASDs). Human genetic studies have identified TBR1 as a high-confidence risk factor for ASDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26578866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "TBR1 regulates autism risk genes in the developing neocortex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27325115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "De novo TBR1 mutations in sporadic autism disrupt protein functions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25232744", "endSection": "title" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1033, "text": "In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23431145", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 212, "text": "It is therefore possible that TBR1 controls the expression of other autism risk factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Neuronal excitation upregulates Tbr1, a high-confidence risk gene of autism, mediating Grin2b expression in the adult brain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25309323", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "T-Brain-1 (TBR1), a causative gene in autism spectrum disorders (ASDs), encodes a brain-specific T-box transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 567, "text": "Recently, recurrent de novo disruptive mutations in the TBR1 gene have been found in patients with autism spectrum disorders (ASDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26578866", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 391, "text": "Here we demonstrate the power of the approach, performing the first functional analyses of TBR1 variants identified in sporadic autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25232744", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1010, "text": "Among these 24 genes, four transcription factors Auts2, Nfia, Nr4a2, and Sox5 were found, suggesting that TBR1 controls a transcriptional cascade relevant to autism pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 210, "text": "Disruptive mutations in the TBR1 gene have been repeatedly identified in patients with autism spectrum disorders (ASDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24441682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "T-Brain-1 (TBR1), a causative gene in autism spectrum disorders (ASDs), encodes a brain-specific T-box transcription factor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1017, "text": "Among these 24 genes, four transcription factors Auts2, Nfia, Nr4a2, and Sox5 were found, suggesting that TBR1 controls a transcriptional cascade relevant to autism pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 210, "text": "Disruptive mutations in the TBR1 gene have been repeatedly identified in patients with autism spectrum disorders (ASDs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24441682", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1018, "text": "Among these 24 genes, four transcription factors Auts2, Nfia, Nr4a2, and Sox5 were found, suggesting that TBR1 controls a transcriptional cascade relevant to autism pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 213, "text": "It is therefore possible that TBR1 controls the expression of other autism risk factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "TBR1 regulates autism risk genes in the developing neocortex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27325115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "De novo TBR1 mutations in sporadic autism disrupt protein functions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25232744", "endSection": "title" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1160, "text": "Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27325115", "endSection": "abstract" } ] }, { "body": "What is the role of the MCM2-7 complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19805216", "http://www.ncbi.nlm.nih.gov/pubmed/15522891", "http://www.ncbi.nlm.nih.gov/pubmed/22045335", "http://www.ncbi.nlm.nih.gov/pubmed/24234446", "http://www.ncbi.nlm.nih.gov/pubmed/23977294", "http://www.ncbi.nlm.nih.gov/pubmed/23376927", "http://www.ncbi.nlm.nih.gov/pubmed/17314092", "http://www.ncbi.nlm.nih.gov/pubmed/21070963", "http://www.ncbi.nlm.nih.gov/pubmed/12059957", "http://www.ncbi.nlm.nih.gov/pubmed/12694531", "http://www.ncbi.nlm.nih.gov/pubmed/12087101", "http://www.ncbi.nlm.nih.gov/pubmed/25319829", "http://www.ncbi.nlm.nih.gov/pubmed/18824790", "http://www.ncbi.nlm.nih.gov/pubmed/19481678", "http://www.ncbi.nlm.nih.gov/pubmed/19357199", "http://www.ncbi.nlm.nih.gov/pubmed/23518502", "http://www.ncbi.nlm.nih.gov/pubmed/24947836", "http://www.ncbi.nlm.nih.gov/pubmed/19540846", "http://www.ncbi.nlm.nih.gov/pubmed/22918581", "http://www.ncbi.nlm.nih.gov/pubmed/23720738", "http://www.ncbi.nlm.nih.gov/pubmed/26582917", "http://www.ncbi.nlm.nih.gov/pubmed/15286659", "http://www.ncbi.nlm.nih.gov/pubmed/23817338", "http://www.ncbi.nlm.nih.gov/pubmed/18606811", "http://www.ncbi.nlm.nih.gov/pubmed/12527764", "http://www.ncbi.nlm.nih.gov/pubmed/15108800", "http://www.ncbi.nlm.nih.gov/pubmed/26940553", "http://www.ncbi.nlm.nih.gov/pubmed/23864661", "http://www.ncbi.nlm.nih.gov/pubmed/19270162", "http://www.ncbi.nlm.nih.gov/pubmed/15653632", "http://www.ncbi.nlm.nih.gov/pubmed/22351771", "http://www.ncbi.nlm.nih.gov/pubmed/21799014", "http://www.ncbi.nlm.nih.gov/pubmed/21460226", "http://www.ncbi.nlm.nih.gov/pubmed/19910535", "http://www.ncbi.nlm.nih.gov/pubmed/21196493" ], "ideal_answer": [ "The MCM2-7 complex is a ring-shaped heterohexamer helicase, that unwinds the DNA double helix ahead of the other replication machinery. During pre-replication complex (pre-RC) formation, origin recognition complex (ORC), Cdc6, and Cdt1 cooperatively load a double-hexameric MCM2-7 complex onto DNA. Loading of MCM2-7 is a prerequisite for licensing of eukaryotic DNA replication. During S phase MCM2-7 functions as part of the replicative helicase but within the pre-RC MCM2-7 is inactive." ], "concepts": [ "http://www.uniprot.org/uniprot/MCM2_YEAST", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064111", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064110", "http://www.uniprot.org/uniprot/MCM2_HUMAN", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064168", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064150", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064148", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064151", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380", "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064126", "http://www.uniprot.org/uniprot/MCM2_ARATH" ], "type": "summary", "id": "58dcd0338acda34529000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The role of the MCM2-7 helicase complex during Arabidopsis seed development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24947836", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The MINICHROMOSOME MAINTENANCE 2-7 (MCM2-7) complex, a ring-shaped heterohexamer, unwinds the DNA double helix ahead of the other replication machinery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24947836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "MCM7 is one of the subunits of the MCM2-7 complex that plays a critical role in DNA replication initiation and cell proliferation of eukaryotic cells. After forming the pre-replication complex (pre-RC) with other components, the MCM2-7 complex is activated by DDK/cyclin-dependent kinase to initiate DNA replication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23720738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Hexameric complexes of the six related Mcm2-7 proteins form the core of the replicative helicase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23518502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "MCM-BP regulates unloading of the MCM2-7 helicase in late S phase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196493", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Origins of DNA replication are licensed by recruiting MCM2-7 to assemble the prereplicative complex (pre-RC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21196493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Mec1 is one of multiple kinases that prime the Mcm2-7 helicase for phosphorylation by Cdc7.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070963", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Activation of the eukaryotic replicative DNA helicase, the Mcm2-7 complex, requires phosphorylation by Cdc7/Dbf4 (Dbf4-dependent kinase or DDK), which, in turn, depends on prior phosphorylation of Mcm2-7 by an unknown kinase (or kinases)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070963", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 339, "text": "The heterohexameric complex of minichromosome maintenance proteins (MCM2-7 complex) plays an essential role in origin licensing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19481678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19910535", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 407, "text": "During pre-replication complex (pre-RC) formation, origin recognition complex (ORC), Cdc6, and Cdt1 cooperatively load the 6-subunit mini chromosome maintenance (MCM2-7) complex onto DNA. Loading of MCM2-7 is a prerequisite for DNA licensing that restricts DNA replication to once per cell cycle. During S phase MCM2-7 functions as part of the replicative helicase but within the pre-RC MCM2-7 is inactive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19910535", "endSection": "abstract" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1592, "text": "The quaternary structure of MCM2-7 changes during pre-RC formation: MCM2-7 before loading is a single hexamer in solution but is transformed into a double-hexamer during pre-RC formation. Using electron microscopy (EM), we observed that loaded MCM2-7 encircles DNA. The loaded MCM2-7 complex can slide on DNA, and sliding is not directional. Our results provide key insights into mechanisms of pre-RC formation and have important implications for understanding the role of the MCM2-7 in establishment of bidirectional replication forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19910535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cdt1 is required for loading the replicative DNA helicase MCM2/7, a process known as DNA replication licensing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23817338", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1013, "text": "Both the Mcm4/6/7 and Mcm2~7 complexes stimulate RNA primer synthesis by DNA primase in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23977294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "MCM7 is one of the subunits of the MCM2-7 complex that plays a critical role in DNA replication initiation and cell proliferation of eukaryotic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23720738", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1190, "text": "These biochemical data suggest that phosphorylation of MCM4 at these sites by CDK plays a direct role in dislodging MCM2-7 from chromatin and/or preventing re-loading of the complex to chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23864661", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 337, "text": "The heterohexameric complex of minichromosome maintenance proteins (MCM2-7 complex) plays an essential role in origin licensing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19481678", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 482, "text": "In this report, we have used bimolecular fluorescence complementation assays in HeLa cells to examine the interactions between Cdc45, Mcm2-7, and the GINS complex (collectively called the CMG complex), which seem to play a key role in the formation and progression of replication forks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19805216", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The origin recognition complex (ORC) of Saccharomyces cerevisiae binds origin DNA and cooperates with Cdc6 and Cdt1 to load the replicative helicase MCM2-7 onto DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376927", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 398, "text": "The CMG (Cdc45\u00b7Mcm2-7\u00b7GINS) complex, which is composed of Cdc45, Mcm2-7, and the GINS (Go-Ichi-Ni-San) complex consisting of Sld5 and Psf1 to Psf3, is recruited by Cdc6 and Cdt1 onto origins bound by the heterohexameric origin recognition complex (ORC) and functions as a replicative helicase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21799014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "MCM7 is one of the subunits of the MCM2-7 complex that plays a critical role in DNA replication initiation and cell proliferation of eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23720738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The MCM2-7 complex, which may act as a replicative helicase during DNA synthesis, plays a central role in S-phase genome stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15108800", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 338, "text": "The heterohexameric complex of minichromosome maintenance proteins (MCM2-7 complex) plays an essential role in origin licensing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19481678", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 594, "text": "In this work, we demonstrate that subunits of the MCM2-7 complex are coordinately expressed during Arabidopsis (Arabidopsis thaliana) development and are abundant in proliferating and endocycling tissues, indicative of a role in DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19357199", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 723, "text": "Cdc6 and Cdt1 play an essential role in DNA replication initiation by loading the Mcm2-7 complex, which is required for unwinding the DNA helix, onto chromosomal origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15522891", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1134, "text": "Inspired by the role of the rigid region in promoters, we speculate that the rigid replication origins may facilitate binding of proteins, including the origin recognition complex (ORC), Cdc6, Cdt1 and the MCM2-7 complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824790", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1220, "text": "Overall, our data identify a new Mcm protein, which does not form part of the Mcm2-7 complex and which is only structure-bound during S phase, thus suggesting its specific role in DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12527764", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 374, "text": "Using Mcm4/6/7 as a tool, we reveal a role for nucleotide binding by Saccharomyces cerevisiae Mcm2 in modulating DNA binding by Mcm complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19540846", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during prereplicative complex formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24234446", "endSection": "title" }, { "offsetInBeginSection": 633, "offsetInEndSection": 825, "text": "Here, structural evidence for intermediates consisting of an ORC-Cdc6-Mcm2-7 complex and an ORC-Cdc6-Mcm2-7-Mcm2-7 complex are reported, which together provide new insights into DNA licensing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25319829", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1593, "text": "Our results provide key insights into mechanisms of pre-RC formation and have important implications for understanding the role of the MCM2-7 in establishment of bidirectional replication forks..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19910535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The Mcm proteins are a family of six homologous proteins (Mcm2-7) that play an important role in DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12694531", "endSection": "abstract" } ] }, { "body": "In which fields of DNA sequencing are Bloom filters applied?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25398208", "http://www.ncbi.nlm.nih.gov/pubmed/27412092", "http://www.ncbi.nlm.nih.gov/pubmed/25252952", "http://www.ncbi.nlm.nih.gov/pubmed/24565280", "http://www.ncbi.nlm.nih.gov/pubmed/25183486", "http://www.ncbi.nlm.nih.gov/pubmed/20472541", "http://www.ncbi.nlm.nih.gov/pubmed/26539459", "http://www.ncbi.nlm.nih.gov/pubmed/27828710" ], "ideal_answer": [ "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters Lighter is a fast, memory-efficient tool for correcting sequencing errors.", "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters. Further, we note that Bloom filters would be suitable to implicitly store spaced seeds and be tolerant to sequencing errors. Lighter avoids counting k-mers. Fast lossless compression via cascading Bloom filters. ", "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters. Instead, it uses a pair of Bloom filters, one holding a sample of the input k-mers and the other holding k-mers likely to be correct. Fast lossless compression via cascading Bloom filters. Lighter is a fast, memory-efficient tool for correcting sequencing errors. ", "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters. Instead, it uses a pair of Bloom filters, one holding a sample of the input k-mers and the other holding k-mers likely to be correct. Lighter is a fast, memory-efficient tool for correcting sequencing errors. Lighter avoids counting k-mers. ", "Bloom Filters (BFs) reduce the memory footprint required to store millions of k-mers while allowing for fast set containment queries, at the cost of a low false positive rate (FPR). Cascading Bloom filters have been used to improve the memory usage and speed of DNA sequence compression.", "Further, we note that Bloom filters would be suitable to implicitly store spaced seeds and be tolerant to sequencing errors. It uses a pair of cache oblivious Bloom filters, one holding a uniform sample of [Formula: see text]-spaced sequenced [Formula: see text]-mers and the other holding [Formula: see text]-mers classified as likely correct, using a simple statistical test." ], "exact_answer": [ [ "storage" ], [ "compression" ], [ "alignment-free comparisons" ] ], "type": "list", "id": "58eb6061eda5a57672000005", "snippets": [ { "offsetInBeginSection": 298, "offsetInEndSection": 492, "text": "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20472541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Classification of DNA sequences using Bloom filters", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20472541", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Lighter is a fast, memory-efficient tool for correcting sequencing errors. Lighter avoids counting k-mers. Instead, it uses a pair of Bloom filters, one holding a sample of the input k-mers and the other holding k-mers likely to be correct.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Fast lossless compression via cascading Bloom filters", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25252952", "endSection": "title" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1661, "text": "In contrast to reference-based methods that first align reads to the genome, we hash all reads into Bloom filters to encode, and decode by querying the same Bloom filters using read-length subsequences of the reference genome. Further compression is achieved by using a cascade of such filters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25252952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Using cascading Bloom filters to improve the memory usage for de Brujin graphs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24565280", "endSection": "title" }, { "offsetInBeginSection": 286, "offsetInEndSection": 446, "text": "In this work, we show how to reduce the memory required by the data structure of Chikhi and Rizk (WABI'12) that represents de Brujin graphs using Bloom filters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24565280", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1006, "text": "We introduce a novel hash-based method for constructing the string graph. We use incremental hashing, and specifically a modification of the Karp-Rabin fingerprint, and Bloom filters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25183486", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1080, "text": "Further, we note that Bloom filters would be suitable to implicitly store spaced seeds and be tolerant to sequencing errors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26539459", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1168, "text": " It uses a pair of cache oblivious Bloom filters, one holding a uniform sample of [Formula: see text]-spaced sequenced [Formula: see text]-mers and the other holding [Formula: see text]-mers classified as likely correct, using a simple statistical test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27412092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Improving Bloom Filter Performance on Sequence Data Using k-mer Bloom Filters", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27828710", "endSection": "title" }, { "offsetInBeginSection": 482, "offsetInEndSection": 647, "text": "BFs reduce the memory footprint required to store millions of k-mers while allowing for fast set containment queries, at the cost of a low false positive rate (FPR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27828710", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1226, "text": "We consider several variants of such k-mer Bloom filters (kBFs), derive theoretical upper bounds for their FPR, and discuss their range of applications and limitations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27828710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Fast lossless compression via cascading Bloom filters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25252952", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Fast lossless compression via cascading Bloom filters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25252952", "endSection": "title" } ] }, { "body": "Which 2 medications are included in the Qsymia pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23590816", "http://www.ncbi.nlm.nih.gov/pubmed/23531960", "http://www.ncbi.nlm.nih.gov/pubmed/24222976", "http://www.ncbi.nlm.nih.gov/pubmed/23565717", "http://www.ncbi.nlm.nih.gov/pubmed/25826792", "http://www.ncbi.nlm.nih.gov/pubmed/25661549", "http://www.ncbi.nlm.nih.gov/pubmed/23039320", "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "http://www.ncbi.nlm.nih.gov/pubmed/24991373", "http://www.ncbi.nlm.nih.gov/pubmed/23625271", "http://www.ncbi.nlm.nih.gov/pubmed/24986038" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0013227", "o": "http://linkedlifedata.com/resource/umls/label/A18591068" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18591068", "o": "pharmaceutical preparations" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0025118", "o": "medicine" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0013227", "o": "http://linkedlifedata.com/resource/umls/label/A18628198" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18628198", "o": "pharmaceutical preparation" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0013227", "o": "http://linkedlifedata.com/resource/umls/label/A18683808" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18683808", "o": "medications" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0013227", "o": "drug" } ], "ideal_answer": [ "Qsymia pill includes phentermine and topiramate. It is used for treatment of obesity." ], "exact_answer": [ [ "phentermine" ], [ "topiramate" ] ], "type": "list", "id": "589a246c78275d0c4a000032", "snippets": [ { "offsetInBeginSection": 235, "offsetInEndSection": 397, "text": "OBJECTIVE: To quantify the incremental cost-effectiveness of Qsymia (phentermine and topiramate extended-release) for health-related quality of life improvements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24986038", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1002, "text": "The intervention was diet and lifestyle advice plus the recommended dose of Qsymia (phentermine 7.5\u00a0mg plus topiramate 46.0\u00a0mg) vs. control, which included diet and lifestyle advice plus placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24986038", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 698, "text": "These include combinations (at low dose) of existing drugs, e.g., bupropion + naltrexone (Contrave), phentermine + topiramate (Qsymia), higher doses of existing drugs licensed for other indications (liraglutide, 3 mg), and new entities (lorcaserin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25661549", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 960, "text": "RECENT FINDINGS: Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 982, "text": "Adding to the current available pharmacotherapies for obesity, the Food and Drug Administration has recently approved 2 new combination medications known as lorcaserin (Belviq) and phentermine-topiramate (Qsymia).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "After a long period of failure in development, two new medications (phentermine/topiramate ER - Qsymia\u2122 and lorcaserin - Belviq\u00ae) have been approved by the US Food and Drug Administration for long-term weight management in persons with obesity (BMI \u2265 30 kg/m(2)) or in overweight persons (BMI \u2265 27 kg/m(2)) with comorbidities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625271", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 952, "text": "The intervention was diet and lifestyle advice plus the recommended dose of Qsymia (phentermine 7.5\u00a0mg plus topiramate 46.0\u00a0mg) vs. control, which included diet and lifestyle advice plus placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24986038", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 924, "text": "Current antiobesity medications and pharmacological strategies will be reviewed.Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 917, "text": "Almost a decade after the Food and Drug Administration approved the first weight loss medication, it recently approved two novel anti-obesity drugs Belviq (lorcaserin) and Qsymia (topiramate and phentermine), thus signalling the beginning of a new era in the pharmacotherapy of obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25826792", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 865, "text": "Obesity is a public health crisis affecting approximately more than 33% of Americans and costing the healthcare system more than $190 billion annually.To review the 2 new drugs that were recently approved by the US Food and Drug Administration (FDA) for the treatment of obesity, lorcaserin HCl (Belviq) and phentermine/topiramate (Qsymia) and their potential impact on the treatment of obese patients.Lifestyle modification is the first and mainstay treatment for obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991373", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 987, "text": "Adding to the current available pharmacotherapies for obesity, the Food and Drug Administration has recently approved 2 new combination medications known as lorcaserin (Belviq) and phentermine-topiramate (Qsymia).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531960", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 925, "text": "Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 795, "text": "To review the 2 new drugs that were recently approved by the US Food and Drug Administration (FDA) for the treatment of obesity, lorcaserin HCl (Belviq) and phentermine/topiramate (Qsymia) and their potential impact on the treatment of obese patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991373", "endSection": "abstract" } ] }, { "body": "Is sonidegib effective for basal cell carcinoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26867946", "http://www.ncbi.nlm.nih.gov/pubmed/27189494", "http://www.ncbi.nlm.nih.gov/pubmed/26566923", "http://www.ncbi.nlm.nih.gov/pubmed/26780190", "http://www.ncbi.nlm.nih.gov/pubmed/26546616", "http://www.ncbi.nlm.nih.gov/pubmed/27695345", "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "http://www.ncbi.nlm.nih.gov/pubmed/27538055", "http://www.ncbi.nlm.nih.gov/pubmed/26833519", "http://www.ncbi.nlm.nih.gov/pubmed/26323341", "http://www.ncbi.nlm.nih.gov/pubmed/24523439", "http://www.ncbi.nlm.nih.gov/pubmed/27511905", "http://www.ncbi.nlm.nih.gov/pubmed/24773312", "http://www.ncbi.nlm.nih.gov/pubmed/25646180", "http://www.ncbi.nlm.nih.gov/pubmed/26614022", "http://www.ncbi.nlm.nih.gov/pubmed/27376162", "http://www.ncbi.nlm.nih.gov/pubmed/27096888", "http://www.ncbi.nlm.nih.gov/pubmed/27636236", "http://www.ncbi.nlm.nih.gov/pubmed/27067394" ], "triples": [ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0007117", "o": "http://linkedlifedata.com/resource/umls/label/A18627521" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18627521", "o": "basal cell carcinomas" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0007117", "o": "http://linkedlifedata.com/resource/umls/label/A0474410" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0474410", "o": "basal cell carcinoma" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/umls/id/C0007117", "o": "BCC" } ], "ideal_answer": [ "Yes. Sonidegib, an oral smoothened antagonist, is indicated for the treatment of adults with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation therapy, or adults with recurrent laBCC following surgery or radiation therapy." ], "exact_answer": "yes", "concepts": [ "https://www.nlm.nih.gov/cgi/mesh/2017/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002280", "http://www.disease-ontology.org/api/metadata/DOID:2513" ], "type": "yesno", "id": "589a246f78275d0c4a000034", "snippets": [ { "offsetInBeginSection": 253, "offsetInEndSection": 556, "text": "This review of the literature aims to describe previous and current treatment options for oral therapy in locally advanced and metastatic NMSC otherwise unamenable to standard treatment. Oral Smoothened (Smo) inhibitors Vismodegib, Sonidegib, and Taladegib have shown to be effective in several trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26566923", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 745, "text": "Sonidegib is a new smoothened inhibitor currently under investigation for treatment of laBCC, which demonstrates a comparable safety profile to vismodegib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26780190", "endSection": "abstract" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1067, "text": "The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26833519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Sonidegib (Odomzo\u00ae), an oral smoothened (SMO) antagonist, is indicated for the treatment of adults with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation therapy, or adults with recurrent laBCC following surgery or radiation therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26867946", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1620, "text": "The acceptable benefit-risk profile of sonidegib, along with a paucity of treatment options and the seriousness of the condition, makes sonidegib an emerging option for the treatment of adults with laBCC that has recurred following surgery or radiation therapy, or in those who are not candidates for surgery or radiation therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26867946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Sonidegib phosphate: new approval for basal cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27376162", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27695345", "endSection": "title" }, { "offsetInBeginSection": 2322, "offsetInEndSection": 2734, "text": "Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group.The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat.Novartis Pharmaceuticals Corporation.Copyright \u00a9 2015 Elsevier Ltd. All rights reserved.Copyright \u00a9 2015 Elsevier Ltd. All rights reserved.5' exoribonucleases that plays a key role in the processing and degradation of a wide variety of RNA substrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16939780", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 93, "text": "RNA exosome is responsible for a wide variety of RNA processing and degradation reactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23143101", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 543, "text": "ability of exosomes to carry and selectively deliver bioactive molecules (e.g., lipids, proteins, and nucleic acids) confers on them the capacity to modulate the activity of receptor cells, even if these cells are located in distant tissues or organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27583248", "endSection": "abstract" }, { "offsetInBeginSection": 1655, "offsetInEndSection": 1759, "text": "Our data show that NKG2D is a likely physiological target for exosome-mediated immune evasion in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18490724", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 126, "text": "Exosomes, a key component of cell paracrine secretion, can exert protective effects in various disease models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26794715", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 568, "text": "Exosome secretion participates in the eradication of obsolete proteins but several findings, essentially in the immune system, indicate that exosomes constitute a potential mode of intercellular communication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16877764", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 413, "text": "Exosomes, nano-sized extracellular vesicles, are believed to play important roles in intercellular communications. This study demonstrates that exosomes released from human macrophages negatively regulate endothelial cell migration through control of integrin trafficking. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24338844", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1551, "text": "We found that the majority of extracellular vesicles in the AH were in the exosome size range, suggesting that miRNAs housed within exosomes may function in communication between AH inflow and outflow tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25619138", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 70, "text": "umor cell-derived exosomes (TEX) suppress functions of immune cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26842680", "endSection": "abstract" } ] }, { "body": "Which factors drive replisome disassembly during DNA replication termination and mitosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28368371" ], "ideal_answer": [ "CUL-2LRR-1 and UBXN-3." ], "exact_answer": [ [ "CUL-2LRR-1" ], [ "UBXN-3" ] ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0006274", "http://amigo.geneontology.org/amigo/term/GO:0030894", "https://meshb.nlm.nih.gov/record/ui?ui=D004261", "https://meshb.nlm.nih.gov/record/ui?ui=D008938" ], "type": "list", "id": "5a6d0b2db750ff445500002d", "snippets": [ { "offsetInBeginSection": 173, "offsetInEndSection": 838, "text": "Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2LRR-1associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2LRR1as a key regulated step during DNA replication termination. Interestingly, however, CMG persists on chromatin until prophase in worms that lack CUL-2LRR-1, but is then removed by a mitotic pathway that requires the CDC-48 cofactor UBXN-3, orthologous to the human tumour suppressor FAF1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "CUL-2 and UBXN-3 drive replisome disassembly during DNA replication termination and\u00a0mitosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368371", "endSection": "title" } ] }, { "body": "Does RNA polymerase II have RNA cleavage activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8798387", "http://www.ncbi.nlm.nih.gov/pubmed/12692127", "http://www.ncbi.nlm.nih.gov/pubmed/25764335", "http://www.ncbi.nlm.nih.gov/pubmed/1379232", "http://www.ncbi.nlm.nih.gov/pubmed/9869639", "http://www.ncbi.nlm.nih.gov/pubmed/1371280", "http://www.ncbi.nlm.nih.gov/pubmed/7513257", "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "http://www.ncbi.nlm.nih.gov/pubmed/8312968", "http://www.ncbi.nlm.nih.gov/pubmed/21454497", "http://www.ncbi.nlm.nih.gov/pubmed/7503982", "http://www.ncbi.nlm.nih.gov/pubmed/17535246" ], "ideal_answer": [ "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.", "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II.", "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process.", "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage.", "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex. The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II", "Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA cleavage. The RNA polymerase II elongation complex.", "yes", "The RNA polymerase II elongation complex.SII is an RNA polymerase II-binding protein that stimulates transcription elongation and also activates nascent transcript cleavage by RNA polymerase II in elongation complexes in vitroFactor-dependent transcription elongation involves nascent RNA cleavage.The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase IIThe eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.Here we show that in the presence of SII and nucleotides, transcript cleavage is detected during SII-dependent elongation but not during SII-independent transcription.Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA.In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage.msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process.Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA cleavage." ], "exact_answer": "yes", "type": "yesno", "id": "5a468785966455904c00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764335", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 325, "text": "msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764335", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 635, "text": "Here we show that a single amino-acid substitution in the trigger loop (TL) of Saccharomyces RNAP II, Rpb1 H1085Y, engenders a gain of intrinsic cleavage activity where the substituted tyrosine appears to participate in acid-base chemistry at alkaline pH for both intrinsic cleavage and nucleotidyl transfer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 395, "text": "By site-directed mutagenesis, we have demonstrated that invariant residues Asp-261 and Glu-262 of the nucleic acid-binding TFIIS Zn ribbon are critical for stimulation of both elongation and RNA cleavage activities of RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA cleavage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7513257", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 324, "text": "RNA in such RNA-RNA polymerase complexes undergoes reactions previously thought to be unique to nascent RNA in ternary complexes with DNA, including TFIIS-dependent cleavage and elongation by 3'-terminal addition of NMP from NTP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7513257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7503982", "endSection": "title" }, { "offsetInBeginSection": 341, "offsetInEndSection": 509, "text": "Here we show that in the presence of SII and nucleotides, transcript cleavage is detected during SII-dependent elongation but not during SII-independent transcription. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7503982", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 775, "text": "under typical transcription conditions, SII is necessary but insufficient to activate RNA cleavage. RNA cleavage could serve to move RNA polymerase II away from the transcriptional impediment and/or permit RNA polymerase II multiple attempts at RNA elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7503982", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 293, "text": "SII is an RNA polymerase II-binding protein that stimulates transcription elongation and also activates nascent transcript cleavage by RNA polymerase II in elongation complexes in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1379232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The RNA polymerase II elongation complex. Factor-dependent transcription elongation involves nascent RNA cleavage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1379232", "endSection": "title" }, { "offsetInBeginSection": 670, "offsetInEndSection": 857, "text": "Cleavage was not restricted to an elongation complex arrested at this particular site, showing that nascent RNA hydrolysis is a general property of RNA polymerase II elongation complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1379232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Elongation factor SII (also known as TFIIS) is an RNA polymerase II binding protein that allows bypass of template arrest sites by activating a nascent RNA cleavage reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8798387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "During gene transcription, the RNA polymerase (Pol) active center can catalyze RNA cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21454497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "During gene transcription, the RNA polymerase (Pol) active center can catalyze RNA cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21454497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 244, "text": "Rpb9, a small subunit of RNA polymerase II, enhances the cleavage stimulation activity of S-II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 996, "text": "These results suggest that both S-II and Rpb9 maintain transcriptional fidelity by stimulating the cleavage activity intrinsic to RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1076, "text": "It is also possible that the transcript cleavage activity of RNA polymerase II represents a proofreading function of the enzyme..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1371280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7503982", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Intrinsic transcript cleavage in yeast RNA polymerase II elongation complexes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12692127", "endSection": "title" } ] }, { "body": "Is there a sequence bias in MNase digestion patterns?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22310051", "http://www.ncbi.nlm.nih.gov/pubmed/23458408", "http://www.ncbi.nlm.nih.gov/pubmed/21206756", "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "http://www.ncbi.nlm.nih.gov/pubmed/22559821", "http://www.ncbi.nlm.nih.gov/pubmed/27185945" ], "ideal_answer": [ "The cutting preference of MNase in combination with size selection generates a sequence-dependent bias in the resulting fragments.", "yes", "Micrococcal nuclease does not substantially bias nucleosome mapping. Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques." ], "exact_answer": "yes", "type": "yesno", "id": "5a4e1882966455904c00000f", "snippets": [ { "offsetInBeginSection": 1127, "offsetInEndSection": 1211, "text": "In addition, unlike MNase, MPE-Fe(II) cleaves nuclear DNA with little sequence bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1600, "text": "These findings collectively indicate that MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Micrococcal nuclease does not substantially bias nucleosome mapping.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310051", "endSection": "title" }, { "offsetInBeginSection": 432, "offsetInEndSection": 565, "text": "MNase has hitherto been very widely used to map nucleosomes, although concerns have been raised over its potential to introduce bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310051", "endSection": "abstract" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1534, "text": "These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310051", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1213, "text": "Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22559821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Standardized collection of MNase-seq experiments enables unbiased dataset comparisons.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22559821", "endSection": "title" }, { "offsetInBeginSection": 260, "offsetInEndSection": 409, "text": "Here, we show that the cutting preference of MNase in combination with size selection generates a sequence-dependent bias in the resulting fragments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21206756", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1210, "text": "We propose that combined MNase/exoIII digestion can be applied to in situ chromatin for unbiased genome-wide mapping of nucleosome positions that is not influenced by DNA sequences at the core/linker junctions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23458408", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1214, "text": "Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22559821", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1193, "text": "Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22559821", "endSection": "abstract" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1535, "text": "These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Micrococcal nuclease does not substantially bias nucleosome mapping.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22310051", "endSection": "title" }, { "offsetInBeginSection": 390, "offsetInEndSection": 561, "text": "We find that maize MNase-hypersensitive (MNase HS) regions localize around active genes and within recombination hotspots, focusing biased gene conversion at their flanks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27185945", "endSection": "abstract" } ] }, { "body": "Is NEMO a zinc finger protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28814200", "http://www.ncbi.nlm.nih.gov/pubmed/21622571", "http://www.ncbi.nlm.nih.gov/pubmed/26224629", "http://www.ncbi.nlm.nih.gov/pubmed/25734227", "http://www.ncbi.nlm.nih.gov/pubmed/24100029", "http://www.ncbi.nlm.nih.gov/pubmed/28035815" ], "ideal_answer": [ "NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain." ], "exact_answer": "yes", "type": "yesno", "id": "5a8a9f18fcd1d6a10c00001a", "snippets": [ { "offsetInBeginSection": 394, "offsetInEndSection": 501, "text": "To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-\u03baB essential modulator)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035815", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 239, "text": "an alteration in the zinc finger domain of NEMO (K392R) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26224629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early Embryogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26224629", "endSection": "title" }, { "offsetInBeginSection": 687, "offsetInEndSection": 726, "text": "our simulations of the zinc finger NEMO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25734227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "An important regulatory domain of NF-[Formula: see text]B Essential Modulator (NEMO) is a ubiquitin-binding zinc finger, with a tetrahedral CYS3HIS1 zinc-coordinating binding site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28814200", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 344, "text": "NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24100029", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 459, "text": " We show here that the NEMO C terminus, comprising the ubiquitin binding region and a zinc finger,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21622571", "endSection": "abstract" } ] }, { "body": "Does TFIIS affect nucleosome positioning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19272450", "http://www.ncbi.nlm.nih.gov/pubmed/17081995", "http://www.ncbi.nlm.nih.gov/pubmed/27754494", "http://www.ncbi.nlm.nih.gov/pubmed/7626141", "http://www.ncbi.nlm.nih.gov/pubmed/21177855", "http://www.ncbi.nlm.nih.gov/pubmed/15808512" ], "ideal_answer": [ "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT", "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. Efficient and rapid nucleosome traversal by RNA polymerase II depends on a combination of transcript elongation factors.", "We now show that although TFIIF or TFIIS alone is modestly stimulatory for nucleosome traversal, both factors together increase transcription through nucleosomes in a synergistic manner. Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. ", "yes", "After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. Histone chaperones and transcription factors TFIIS, TFIIF and FACT facilitate transcription through chromatin using different molecular mechanisms. Although TFIIF or TFIIS alone is modestly stimulatory for nucleosome traversal, both factors together increase transcription through nucleosomes in a synergistic manner.", "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. " ], "exact_answer": "yes", "type": "yesno", "id": "5a3566bb966455904c000003", "snippets": [ { "offsetInBeginSection": 813, "offsetInEndSection": 942, "text": "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15808512", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 499, "text": "The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17081995", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 751, "text": "The system contains natural or recombinant histones, chromatin assembly factors, the histone-acetyltransferase p300, all components of the general transcription machinery, general coactivators and the elongation factor SII (TFIIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19272450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Efficient and rapid nucleosome traversal by RNA polymerase II depends on a combination of transcript elongation factors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177855", "endSection": "title" }, { "offsetInBeginSection": 272, "offsetInEndSection": 458, "text": "We now show that although TFIIF or TFIIS alone is modestly stimulatory for nucleosome traversal, both factors together increase transcription through nucleosomes in a synergistic manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177855", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 863, "text": "Significantly, we found that nucleosomes with a Sin mutant histone are traversed to the same extent and at nearly the same rate as equivalent pure DNA templates if both TFIIS and TFIIF are present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177855", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 696, "text": "After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. Histone chaperones and transcription factors TFIIS, TFIIF and FACT facilitate transcription through chromatin using different molecular mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27754494", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 941, "text": "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15808512", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 618, "text": "The highly conserved eukaryotic transcriptional elongation factor TFIIS enables RNA polymerase II (RNAPII) to read though pause or termination sites, nucleosomes and sequence-specific DNA-binding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7626141", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 569, "text": "We also studied the effect of TFIIF and TFIIS on transcription of nucleosomes containing a Sin mutant histone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177855", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 500, "text": "The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17081995", "endSection": "abstract" } ] }, { "body": "Which two cotransporters are inhibited by sotagliflozin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28811850", "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "http://www.ncbi.nlm.nih.gov/pubmed/28387957", "http://www.ncbi.nlm.nih.gov/pubmed/28899222", "http://www.ncbi.nlm.nih.gov/pubmed/28872070", "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "http://www.ncbi.nlm.nih.gov/pubmed/26484403", "http://www.ncbi.nlm.nih.gov/pubmed/25759591", "http://www.ncbi.nlm.nih.gov/pubmed/25690134" ], "ideal_answer": [ "Sotagliflozin works by inhibiting sodium-glucose cotransporter 1 (SGLT1) and sodium-glucose cotransporter 2 (SGLT2). It is used for treatment of diabetes." ], "exact_answer": [ [ "sodium-glucose cotransporter 1" ], [ "sodium-glucose cotransporter 2" ] ], "type": "list", "id": "5a7238d32dc08e987e000009", "snippets": [ { "offsetInBeginSection": 381, "offsetInEndSection": 724, "text": "The present study used molecular docking by Autodock4.2 using our \"Click-By-Click\"-protocol, Ligplot1.4.3 and \"change in accessible surface area (\u0394ASA)-calculations\" to investigate the binding of two investigational anti-diabetic drugs, Ertugliflozin and Sotagliflozin to an established target (SGLT2) and a research target (human brain AChE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28387957", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 607, "text": "SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28811850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Hydrogen-bonded structures and interaction energies in two forms of the SGLT-2 inhibitor sotagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28872070", "endSection": "title" }, { "offsetInBeginSection": 120, "offsetInEndSection": 307, "text": "We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28899222", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1447, "text": "Phase 2 studies with the SGLT2 inhibitor empagliflozin and the dual SGLT1 and SGLT2 inhibitor sotagliflozin, which acts in the gut and the kidney, have demonstrated reductions in A1C, weight, and glucose variability without an increased incidence of hypoglycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26484403", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 310, "text": "Sotagliflozin may meet this need, because this compound lowers blood glucose through the insulin-independent mechanisms of inhibiting kidney SGLT2 and intestinal SGLT1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759591", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 604, "text": "AREAS COVERED: Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1219, "text": "Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 669, "text": "Therefore, sotagliflozin (LX4211) has been developed as a dual inhibitor of SGLT1 and SGLT2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25690134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 446, "text": "OBJECTIVE: To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes.RESEARCH DESIGN AND METHODS: We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "endSection": "abstract" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1663, "text": "CONCLUSIONS: As adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 306, "text": "We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28899222", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1175, "text": "Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "OBJECTIVE To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 668, "text": "Therefore, sotagliflozin (LX4211) has been developed as a dual inhibitor of SGLT1 and SGLT2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25690134", "endSection": "abstract" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1669, "text": "CONCLUSIONS As adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 605, "text": "AREAS COVERED Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "endSection": "abstract" } ] }, { "body": "What is the administration route of IVIG in Alzheimer's disease patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24760109" ], "ideal_answer": [ "IVIG is administered intravenously." ], "exact_answer": [ "Intravenous" ], "type": "factoid", "id": "5a7d51dafaa1ab7d2e000017", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 138, "text": "ntravenous immunoglobulin (IVIG) treatment exerts antioxidant and neuropreservatory effects in preclinical models of Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760109", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Intravenous immunoglobulin (IVIG) has shown limited promise so far in human clinical studies on Alzheimer's disease (AD), yet overwhelmingly positive preclinical work in animals and human brain cultures support the notion that the therapy remains potentially efficacious.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760109", "endSection": "abstract" } ] }, { "body": "What is metaSPAdes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28298430", "http://www.ncbi.nlm.nih.gov/pubmed/29036597", "http://www.ncbi.nlm.nih.gov/pubmed/28948103" ], "ideal_answer": [ "MetaSPAdes is a new versatile metagenomic assembler.", "While metagenomics has emerged as a technology of choice for analyzing bacterial populations, the assembly of metagenomic data remains challenging, thus stifling biological discoveries. Moreover, recent studies revealed that complex bacterial populations may be composed from dozens of related strains, thus further amplifying the challenge of metagenomic assembly. MetaSPAdes is a new versatile metagenomic assembler which addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes." ], "type": "summary", "id": "5a80d965faa1ab7d2e000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "metaSPAdes: a new versatile metagenomic assembler.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28298430", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 564, "text": "While metagenomics has emerged as a technology of choice for analyzing bacterial populations, the assembly of metagenomic data remains challenging, thus stifling biological discoveries. Moreover, recent studies revealed that complex bacterial populations may be composed from dozens of related strains, thus further amplifying the challenge of metagenomic assembly. metaSPAdes addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28298430", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 563, "text": "metaSPAdes addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28298430", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1313, "text": "Faucet used orders of magnitude less time and disk space than the specialized metagenome assemblers MetaSPAdes and Megahit, while also improving on their memory use; this broadly matched performance of other assemblers optimizing resource efficiency-namely, Minia and LightAssembler.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29036597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "metaspades a new versatile metagenomic assembler.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28298430", "endSection": "title" }, { "offsetInBeginSection": 366, "offsetInEndSection": 725, "text": "metaspades addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes. we benchmark metaspades against other state-of-the-art metagenome assemblers and demonstrate that it results in high quality assemblies across diverse data sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28298430", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 853, "text": "Tools specifically designed for metagenomes, specifically metaSPAdes, MEGAHIT, and IDBA-UD, were the most effective at assembling viromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28948103", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1292, "text": "Faucet used orders of magnitude less time and disk space than the specialized metagenome assemblers MetaSPAdes and Megahit, while also improving on their memory use; this broadly matched performance of other assemblers optimizing resource efficiency-namely, Minia and LightAssembler.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29036597", "endSection": "abstract" } ] }, { "body": "What is measured through the NOMe-Seq methodology?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26484155", "http://www.ncbi.nlm.nih.gov/pubmed/28222791", "http://www.ncbi.nlm.nih.gov/pubmed/22960375", "http://www.ncbi.nlm.nih.gov/pubmed/27899623", "http://www.ncbi.nlm.nih.gov/pubmed/25747664", "http://www.ncbi.nlm.nih.gov/pubmed/24916973", "http://www.ncbi.nlm.nih.gov/pubmed/21835883", "http://www.ncbi.nlm.nih.gov/pubmed/28653622", "http://www.ncbi.nlm.nih.gov/pubmed/25530820", "http://www.ncbi.nlm.nih.gov/pubmed/28413449", "http://www.ncbi.nlm.nih.gov/pubmed/22479200", "http://www.ncbi.nlm.nih.gov/pubmed/28035030" ], "ideal_answer": [ "We have developed a method (NOMe-seq) that uses a GpC methyltransferase (M.CviPI) and next generation sequencing to generate a high resolution footprint of nucleosome positioning genome-wide using less than 1 million cells while retaining endogenous DNA methylation information from the same DNA strand. DNaseI-seq and NOMe-seq.", "NOMe-seq is a method that uses a GpC methyltransferase (M.CviPI) and next generation sequencing to generate a high resolution footprint of nucleosome positioning genome-wide using less than 1 million cells while retaining endogenous DNA methylation information from the same DNA strand." ], "exact_answer": [ "Nucleosome positioning and DNA methylation" ], "type": "factoid", "id": "5a43a139966455904c000008", "snippets": [ { "offsetInBeginSection": 783, "offsetInEndSection": 1081, "text": "Using Nucleosome Occupancy Methylome- Sequencing, NOMe-Seq, a single-molecule, high-resolution nucleosome positioning assay, we demonstrate that active, but not inactive, non-CpG island promoters display a nucleosome-depleted region (NDR) immediately upstream of the transcription start site (TSS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835883", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 1080, "text": " Using Nucleosome Occupancy Methylome- Sequencing, NOMe-Seq, a single-molecule, high-resolution nucleosome positioning assay, we demonstrate that active, but not inactive, non-CpG island promoters display a nucleosome-depleted region (NDR) immediately upstream of the transcription start site (TSS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835883", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 1068, "text": "According to our genome-wide expression and DNA methylation profiles, we find that the complete re-activation of silenced genes requires the insertion of the histone variant H2A.Z, which facilitates the acquisition of regions fully depleted of nucleosome as demonstrated by NOMe-seq (Nucleosome Occupancy Methylome-sequencing) assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22479200", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 559, "text": "We have developed a method (NOMe-seq) that uses a GpC methyltransferase (M.CviPI) and next generation sequencing to generate a high resolution footprint of nucleosome positioning genome-wide using less than 1 million cells while retaining endogenous DNA methylation information from the same DNA strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960375", "endSection": "title" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1307, "text": "Importantly, NOMe-seq obtains DNA methylation and nucleosome positioning information from the same DNA molecule, giving the first genome-wide DNA methylation and nucleosome positioning correlation at the single molecule, and thus, single cell level, that can be used to monitor disease progression and response to therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960375", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 520, "text": "Here, we evaluate the scope of global epigenetic alterations at enhancers and insulator elements in prostate and breast cancer cells using simultaneous genome-wide mapping of DNA methylation and nucleosome occupancy (NOMe-seq). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916973", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 833, "text": "Nucleosome Occupancy and Methylome sequencing (NOMe-seq) was used to determine the allele-specific positioning of nucleosomes around heterozygous splice site mutations in lymphoblastoid cells lines (LCLs) derived from six Lynch syndrome patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25530820", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 697, "text": "To address this we used Nucleosome Occupancy and Methylation sequencing (NOMe-seq) to compare the genome-wide DNA methylation and nucleosome occupancy profiles between normal and cancer cell line models of the breast and prostate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26484155", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 935, "text": "Here we describe the bioinformatic pipeline and methods that we developed for the processing and analysis of the NOMe-seq data published by (Taberlay et al., 2014 [1]) and deposited in the Gene Expression Omnibus with accession GSE57498.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26484155", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 455, "text": "The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised, and inactive genomic elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25747664", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 521, "text": "TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899623", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1404, "text": "Finally, these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899623", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 595, "text": "Recently, Methyltransferase Accessibility Protocol for individual templates-Bisulfite Genome Sequencing (MAPit-BGS) and nucleosome occupancy and methylome sequencing (NOMe-seq) have been developed for simultaneously profiling chromatin accessibility and DNA methylation on single molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035030", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 386, "text": "Here I adapted Nucleosome Occupancy and Methylome-sequencing (NOMe-seq) to measure chromatin accessibility and endogenous DNA methylation in single cells (scNOMe-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28653622", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 606, "text": "Recently, Methyltransferase Accessibility Protocol for individual templates-Bisulfite Genome Sequencing (MAPit-BGS) and nucleosome occupancy and methylome sequencing (NOMe-seq) have been developed for simultaneously profiling chromatin accessibility and DNA methylation on single molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035030", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 461, "text": "We develop a statistical method, epiG, to infer and differentiate between different epi-allelic haplotypes, annotated with CpG methylation status and DNA polymorphisms, from whole-genome bisulfite sequencing data, and nucleosome occupancy from NOMe-seq data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28222791", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 744, "text": "In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28413449", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 812, "text": "Nucleosome Occupancy and Methylome sequencing (NOMe-seq) was used to determine the allele-specific positioning of nucleosomes around heterozygous splice site mutations in lymphoblastoid cells lines (LCLs) derived from six Lynch syndrome patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25530820", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 519, "text": "Here, we evaluate the scope of global epigenetic alterations at enhancers and insulator elements in prostate and breast cancer cells using simultaneous genome-wide mapping of DNA methylation and nucleosome occupancy (NOMe-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916973", "endSection": "abstract" } ] }, { "body": "What is the function of the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22833514", "http://www.ncbi.nlm.nih.gov/pubmed/12446625", "http://www.ncbi.nlm.nih.gov/pubmed/23819907", "http://www.ncbi.nlm.nih.gov/pubmed/20023019", "http://www.ncbi.nlm.nih.gov/pubmed/15353557", "http://www.ncbi.nlm.nih.gov/pubmed/25659138", "http://www.ncbi.nlm.nih.gov/pubmed/23651670", "http://www.ncbi.nlm.nih.gov/pubmed/28255560", "http://www.ncbi.nlm.nih.gov/pubmed/22719925", "http://www.ncbi.nlm.nih.gov/pubmed/22544737", "http://www.ncbi.nlm.nih.gov/pubmed/24939385", "http://www.ncbi.nlm.nih.gov/pubmed/22439727", "http://www.ncbi.nlm.nih.gov/pubmed/25535276", "http://www.ncbi.nlm.nih.gov/pubmed/22759512", "http://www.ncbi.nlm.nih.gov/pubmed/19487478", "http://www.ncbi.nlm.nih.gov/pubmed/19795912" ], "ideal_answer": [ "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state.", "The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence to anti-tuberculosis drugs. The DosR regulon enables the pathogen to persist during lengthy hypoxia. Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP). During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions." ], "type": "summary", "id": "58edfaf4eda5a57672000012", "snippets": [ { "offsetInBeginSection": 391, "offsetInEndSection": 841, "text": "The discovery that the tubercle bacillus can develop a drug-tolerant dormant form and the identification of the underlying genetic program 10 years ago paved the way for a deeper understanding of the life of the parasite inside human lesions and for new approaches to antimycobacterial drug discovery. Here, we summarize what we have learnt since the discovery of the master regulator of dormancy, DosR, and the key gaps in our knowledge that remain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22439727", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1135, "text": "M. tb-expanded CD4+CD25+ (85% Foxp3(+)) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25659138", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 431, "text": "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651670", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 438, "text": "The non-replicating or dormancy like state of this pathogen which is impervious to anti-tuberculosis drugs is widely recognized as the culprit for this scenario. The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22833514", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 827, "text": "The DosR regulon enables the pathogen to persist during lengthy hypoxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22833514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651670", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 337, "text": "The dormancy survival (Dos) regulon, regulated by the response regulator DosR, appears to be essential for hypoxic survival in M. tuberculosis, but it is not known how the regulon promotes survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544737", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 374, "text": "The dormancy survival regulon (DosR regulon) is chiefly responsible for encoding dormancy related functions of M. tuberculosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22719925", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1249, "text": "Our results demonstrate induction of dosR (Rv3133c) and 20 other members of the DosR regulon believed to mediate the transition into dormancy, and that rel(Mtb) is required for Mycobacterium tuberculosis survival during extracellular persistence within host granulomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15353557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium tuberculosis dormancy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19487478", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "In Mycobacterium tuberculosis, the sensor kinases DosT and DosS activate the transcriptional regulator DosR, resulting in the induction of the DosR regulon, which is important for anaerobic survival and perhaps latent infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19487478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20023019", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The DosR dormancy regulator of Mycobacterium tuberculosis stimulates the Na(+)/K (+) and Ca (2+) ATPase activities in plasma membrane vesicles of mycobacteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24939385", "endSection": "title" }, { "offsetInBeginSection": 100, "offsetInEndSection": 226, "text": "DosR/DevR of M. tuberculosis is a two component dormancy survival response regulator which induces the expression of 48 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22759512", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 438, "text": "The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22833514", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 719, "text": "DosR (Dormancy Survival Regulator, Rv3133c) regulon genes are expressed under the conditions of latency/dormancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19795912", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1462, "text": "Based on these two functions, dormancy survival and regulation, we named the Rv3133c gene dosR for dormancy survival regulator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12446625", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 738, "text": "A binding motif similar to the dormancy survival regulator (DosR) binding site of M. tuberculosis has been identified in the upstream sequences of most genes in these loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25535276", "endSection": "abstract" }, { "offsetInBeginSection": 1463, "offsetInEndSection": 1597, "text": "Our results provide conclusive evidence that DosR is a key regulator in the oxygen starvation-induced mycobacterial dormancy response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12446625", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1139, "text": "M. tb-expanded CD4+CD25+ (85% Foxp3(+)) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25659138", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 194, "text": "Dormancy survival regulator (DosR) regulon-encoded proteins may have a role in the maintenance of LTBI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28255560", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 294, "text": "The proteins encoded by the dormancy survival regulon (DosR regulon) are mainly responsible for survival of the bacilli in a latent form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23819907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "How Mycobacterium tuberculosis goes to sleep: the dormancy survival regulator DosR a decade later.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22439727", "endSection": "title" }, { "offsetInBeginSection": 565, "offsetInEndSection": 649, "text": "A binding motif similar to the dormancy survival regulator (DosR) binding site of M.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25535276", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 268, "text": "The dormancy survival (Dos) regulon, regulated by the response regulator DosR, appears to be essential for hypoxic survival in M.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The DosR dormancy regulator of Mycobacterium tuberculosis stimulates the Na(+)/K (+) and Ca (2+) ATPase activities in plasma membrane vesicles of mycobacteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24939385", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium tuberculosis dormancy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19487478", "endSection": "title" } ] }, { "body": "Which are the effects of ALDH2 deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26173414", "http://www.ncbi.nlm.nih.gov/pubmed/25831092", "http://www.ncbi.nlm.nih.gov/pubmed/27488451", "http://www.ncbi.nlm.nih.gov/pubmed/28257851" ], "ideal_answer": [ "In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. Diabetic patients with ALDH2 mutations are predisposed to worse diastolic dysfunction.\nThese data demonstrate that ALDH2 deficiency enhances EtOH-induced disruption of intestinal epithelial tight junctions, barrier dysfunction, and liver damage." ], "type": "summary", "id": "5a894f6abc7bade53a000004", "snippets": [ { "offsetInBeginSection": 136, "offsetInEndSection": 363, "text": "The genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans provides strong evidence for the causal relationship between acetaldehyde-exposure due to alcohol consumption and cancer of the upper digestive tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28257851", "endSection": "abstract" }, { "offsetInBeginSection": 2032, "offsetInEndSection": 2118, "text": "Diabetic patients with ALDH2 mutations are predisposed to worse diastolic dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27488451", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 371, "text": "In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25831092", "endSection": "abstract" }, { "offsetInBeginSection": 1932, "offsetInEndSection": 2155, "text": "eater in ALDH2(+/-) mice compared to wild-type mice.CONCLUSIONS: These data demonstrate that ALDH2 deficiency enhances EtOH-induced disruption of intestinal epithelial tight junctions, barrier dysfunction, and liver damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26173414", "endSection": "abstract" } ] }, { "body": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9311882", "http://www.ncbi.nlm.nih.gov/pubmed/8107218" ], "ideal_answer": [ "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA.", "PET (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA.", "In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. This element, which we have named pet , exerts its effect in cis in a position and orientation-dependent manner, suggesting that pregenome transcription complexes fail to reach the downstream promoters. We speculate that pet , exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. ", "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript.In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters.In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template.We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA.", "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template.", "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript.", "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. ", "This element, which we have named pet , exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. " ], "type": "summary", "id": "5916f14070f9fc6f0f00001f", "snippets": [ { "offsetInBeginSection": 220, "offsetInEndSection": 446, "text": "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8107218", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 1174, "text": "In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8107218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "We report the presence of two elements, pet and net, that are required for proper transcription of the duck hepatitis B virus (DHBV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9311882", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 445, "text": "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8107218", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 651, "text": "We observed that pet was required for pregenome transcription from circular viral monomers, and in the absence of pet-dependent transcription, expression of the viral envelope genes was increased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9311882", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 664, "text": "The requirement for pet depends on the presence in the transcription unit of a region of the DHBV genome located upstream of the envelope promoters, which specifically suppresses transcription of templates lacking pet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8107218", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 978, "text": "In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8107218", "endSection": "abstract" } ] }, { "body": "What is the role of Kmt5a in liver?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28746875" ], "ideal_answer": [ "H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. In non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted in an energy starvation condition partially compensated by AMP-activated protein kinase (AMPK) activation and increased mitochondrial activity. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage.", "Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions. H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage. The results illustrate how defects in the general process of RNA Pol II transition into a productive elongation phase can trigger specific metabolic changes and genome instability." ], "concepts": [ "http://www.uniprot.org/uniprot/KMT5A_MOUSE", "http://www.uniprot.org/uniprot/KT5AA_XENLA", "http://www.uniprot.org/uniprot/KMT5A_XENTR", "http://amigo.geneontology.org/amigo/term/GO:0001889", "http://www.uniprot.org/uniprot/KMT5A_HUMAN", "http://www.uniprot.org/uniprot/KT5AA_DANRE", "https://meshb.nlm.nih.gov/record/ui?ui=D008099", "http://www.uniprot.org/uniprot/KT5AB_XENLA", "http://www.uniprot.org/uniprot/KMT5A_BOVIN" ], "type": "summary", "id": "5a80d6cbfaa1ab7d2e000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28746875", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1177, "text": "H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. Here, we show that, in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted in an energy starvation condition partially compensated by AMP-activated protein kinase (AMPK) activation and increased mitochondrial activity. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage. The results illustrate how defects in the general process of RNA Pol II transition into a productive elongation phase can trigger specific metabolic changes and genome instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28746875", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 482, "text": "In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me correlated with reduced RNA Pol II release from promoter-proximal regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28746875", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 483, "text": "In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28746875", "endSection": "abstract" } ] }, { "body": "Is tretinoin effective for photoaging?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7544967", "http://www.ncbi.nlm.nih.gov/pubmed/28762645", "http://www.ncbi.nlm.nih.gov/pubmed/8435921", "http://www.ncbi.nlm.nih.gov/pubmed/26885791", "http://www.ncbi.nlm.nih.gov/pubmed/2186790", "http://www.ncbi.nlm.nih.gov/pubmed/25603890", "http://www.ncbi.nlm.nih.gov/pubmed/28293257", "http://www.ncbi.nlm.nih.gov/pubmed/3336176", "http://www.ncbi.nlm.nih.gov/pubmed/16724545", "http://www.ncbi.nlm.nih.gov/pubmed/10790815", "http://www.ncbi.nlm.nih.gov/pubmed/27050699", "http://www.ncbi.nlm.nih.gov/pubmed/11535421", "http://www.ncbi.nlm.nih.gov/pubmed/9703125", "http://www.ncbi.nlm.nih.gov/pubmed/1552056", "http://www.ncbi.nlm.nih.gov/pubmed/9486677", "http://www.ncbi.nlm.nih.gov/pubmed/25141855", "http://www.ncbi.nlm.nih.gov/pubmed/24734193", "http://www.ncbi.nlm.nih.gov/pubmed/9589209" ], "ideal_answer": [ "Yes, Tretinoin is commonly used topically in the treatment of photoaging." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014212" ], "type": "yesno", "id": "5a68f2bab750ff4455000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Background. Tretinoin has been shown to improve photoaged skin. This study was designed to evaluate the efficacy and tolerability of a 5% retinoic acid peel combined with microdermabrasion for facial photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293257", "endSection": "abstract" }, { "offsetInBeginSection": 1113, "offsetInEndSection": 1296, "text": ".Conclusion. This study demonstrated that 5% retinoic acid peel cream combined with microdermabrasion was safe and effective in the treatment of photoaging in the Iranian population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293257", "endSection": "abstract" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 1717, "text": "CONCLUSIONS: Treatment with a double-conjugate retinoid cream demonstrated early reductions in photodamage and improvements in Hydration. AHA-Ret induced less Erythema vs retinol and was more tolerable vs retinol and tretinoin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28762645", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 939, "text": "These comparative products include prescription tretinoin, physician strength idebenone, kinetin, polyhydroxy, lactic and glycolic acids in reversing signs of photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26885791", "endSection": "abstract" }, { "offsetInBeginSection": 1888, "offsetInEndSection": 2073, "text": "CONCLUSION: Either topical tretinoin (0.25%) or retinol (0.25%) can be used safely and effectively when applied in office immediately after SA peeling to ameliorate signs of photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27050699", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1596, "text": "CONCLUSION: The treatment outcome of Retinol 0.2%/LR2412 2% cream does not differ from the one of tretinoin 0.025% cream. Clinical results were not statistically different. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25603890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "INTRODUCTION: Topical tretinoin is considered the gold standard to treat photoaged skin, but it is associated with side effects and only available upon prescription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25603890", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 372, "text": "Tretinoin is commonly used topically for acne treatment and in the treatment of photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24734193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "BACKGROUND: Topical tretinoin is effective treatment for both acne and photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9486677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The efficacy of tretinoin is well established in the treatment of acne and photoaged skin, however as a typical side effect of tretinoin treatment most patients develop a low-grade irritant dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16724545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Topical tretinoin is established as an effective treatment for photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9703125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "BACKGROUND Topical tretinoin is effective treatment for both acne and photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9486677", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 319, "text": "Tretinoin is the only pharmacologic compound shown to partially reverse some signs of photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8435921", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 214, "text": "Although once considered an irreversible process, it is now established that photoaging can be treated by topical tretinoin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9589209", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 754, "text": "Moreover, studies that have elucidated photoaging pathophysiology have produced significant evidence that topical tretinoin (all-trans retinoic acid), the only agent approved so far for the treatment of photoaging, also works to prevent it.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11535421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "BACKGROUND AND DESIGN The efficacy of topical tretinoin (all-trans-retinoic acid) in treating photoaging is well established.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7544967", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 404, "text": "MAJOR CONCLUSIONS Tretinoin can be used for photoaging treatment or combined treatment by different mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25141855", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 290, "text": "Tretinoin is still the best tested retinoid to reverse photoaged skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25141855", "endSection": "abstract" }, { "offsetInBeginSection": 1872, "offsetInEndSection": 2036, "text": "The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoin-induced repair of photoaging in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7544967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "* A cream containing 0.05% tretinoin (Retinova((R)) is approved for treatment of sun-induced skin damage (\"photoaging\").", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10790815", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 656, "text": "Randomized, controlled trials have shown that topical tretinoin is effective in the treatment of photoaged skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2186790", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 63, "text": "Tretinoin has been shown to improve photoaged skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Topical tretinoin is effective treatment for both acne and photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9486677", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 657, "text": "Randomized, controlled trials have shown that topical tretinoin is effective in the treatment of photoaged skin..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2186790", "endSection": "abstract" }, { "offsetInBeginSection": 1636, "offsetInEndSection": 1740, "text": "Tretinoin emollient cream 0.05% appears to be safe and effective in the treatment of photodamaged skin..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1552056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3336176", "endSection": "title" } ] }, { "body": "What is the difference between ganglion mother cells (GMC) and intermediate neural precursor cells (INP) in Drosophila?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9637687", "http://www.ncbi.nlm.nih.gov/pubmed/11688564", "http://www.ncbi.nlm.nih.gov/pubmed/9192868", "http://www.ncbi.nlm.nih.gov/pubmed/23376107", "http://www.ncbi.nlm.nih.gov/pubmed/18342578", "http://www.ncbi.nlm.nih.gov/pubmed/25129108", "http://www.ncbi.nlm.nih.gov/pubmed/14973280", "http://www.ncbi.nlm.nih.gov/pubmed/15704126", "http://www.ncbi.nlm.nih.gov/pubmed/25285448", "http://www.ncbi.nlm.nih.gov/pubmed/8095484", "http://www.ncbi.nlm.nih.gov/pubmed/22357926" ], "ideal_answer": [ "GMC divides only once to give rise to two post-mitotic cells (neurons or glia), whereas the INP can also self-renew, albeit for fewer rounds than a NSC, and generate GMCs" ], "type": "summary", "id": "59d09a0cbc32f93e6d000001", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 268, "text": " Neuroblasts (NBs) give rise to differentiated neurons and glia via intermediate precursors called GMCs or INPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357926", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 819, "text": "Expression of E(spl)m\u03b3 and m8, but not of dpn, depends on Notch signalling from the GMC/INP daughter to the NB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "A new role of Klumpfuss in establishing cell fate during the GMC asymmetric cell division.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129108", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Studies in the Drosophila embryonic NB4-2 lineage have suggested that the transcription factor Klumpfuss (Klu) functions within embryonic neuroblast lineages to differentiate between the identities of two adjacent ganglion mother cells (GMCs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129108", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 910, "text": "Unexpectedly, in this lineage, klu is necessary for differentiating between the fates of the two neurons born from a unique GMC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129108", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1144, "text": "Additionally, our results demonstrate that Klu operates in the GMC and/or in the newly born neuron, but not in the neuroblast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Neural progenitors of the Drosophila larval brain, called neuroblasts, can be divided into distinct populations based on patterns of proliferation and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "In both vertebrates and insects, neurons typically arise from neural stem cells or terminally dividing intermediate progenitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18342578", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 489, "text": "Each NB has a unique identity and undergoes repeated cell divisions to produce several smaller secondary precursor cells, ganglion mother cells (GMCs); each GMC divides once to produce two neurons and/or glia, thereby generating a specific lineage of neurons/glia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9192868", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 419, "text": "Type I neuroblasts produce ganglion mother cells (GMCs) that divide once to produce differentiated progeny, while type II neuroblasts produce self-renewing intermediate neural progenitors (INPs) and thus generate lineages containing many more progeny.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23376107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "In the Drosophila CNS, neuroblasts undergo self-renewing asymmetric divisions, whereas their progeny, ganglion mother cells (GMCs), divide asymmetrically to generate terminal postmitotic neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14973280", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 531, "text": "NBs divide asymmetrically to regenerate themselves and produce a secondary precursor cell called a ganglion mother cell (GMC), which divides to produce neurons and glia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15704126", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 347, "text": "Each of the approximately 25 NBs per hemisegment undergoes repeated asymmetric divisions to produce, on average, 5-10 smaller ganglion mother cells (GMCs); each GMC, in turn, divides to produce two neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8095484", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 622, "text": "We show that the loss of Btd leads to elimination of mature INPs due to premature differentiation of INPs into terminally dividing ganglion mother cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25285448", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 317, "text": "In the embryonic central nervous system of Drosophila melanogaster, secondary precursor cells-ganglion mother cells (GMCs)-divide and produce postmitotic neurons that take on different cell fates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9637687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The bipotential Ganglion Mother Cells, or GMCs, in the Drosophila CNS asymmetrically divide to generate two distinct post-mitotic neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11688564", "endSection": "abstract" } ] }, { "body": "What is the FIRE (Functional Inference of Regulators of Expression) tool?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28961785" ], "ideal_answer": [ "FIRE (Functional Inference of Regulators of Expression) is a tool to score both noncoding and coding SNVs based on their potential to regulate the expression levels of nearby genes.", "Methods to predict whether or not individual SNVs are likely to regulate gene expression would aid interpretation of variants of unknown significance identified in whole-genome sequencing studies. FIRE (Functional Inference of Regulators of Expression) is a tool to score both noncoding and coding SNVs based on their potential to regulate the expression levels of nearby genes. FIRE consists of 23 random forests trained to recognize SNVs in cis -expression quantitative trait loci (cis -eQTLs) using a set of 92 genomic annotations as predictive features." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0010468", "https://meshb.nlm.nih.gov/record/ui?ui=D018507", "https://meshb.nlm.nih.gov/record/ui?ui=D005786", "https://meshb.nlm.nih.gov/record/ui?ui=D015971", "https://meshb.nlm.nih.gov/record/ui?ui=D015966", "https://meshb.nlm.nih.gov/record/ui?ui=D015967", "https://meshb.nlm.nih.gov/record/ui?ui=D015964", "https://meshb.nlm.nih.gov/record/ui?ui=D015870" ], "type": "summary", "id": "5a760c8483b0d9ea66000017", "snippets": [ { "offsetInBeginSection": 281, "offsetInEndSection": 1240, "text": "Methods to predict whether or not individual SNVs are likely to regulate gene expression would aid interpretation of variants of unknown significance identified in whole-genome sequencing studies.Results: We developed FIRE (Functional Inference of Regulators of Expression), a tool to score both noncoding and coding SNVs based on their potential to regulate the expression levels of nearby genes. FIRE consists of 23 random forests trained to recognize SNVs in cis -expression quantitative trait loci ( cis -eQTLs) using a set of 92 genomic annotations as predictive features. FIRE scores discriminate cis -eQTL SNVs from non-eQTL SNVs in the training set with a cross-validated area under the receiver operating characteristic curve (AUC) of 0.807, and discriminate cis -eQTL SNVs shared across six populations of different ancestry from non-eQTL SNVs with an AUC of 0.939. FIRE scores are also predictive of cis -eQTL SNVs across a variety of tissue types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961785", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 658, "text": "We developed FIRE (Functional Inference of Regulators of Expression), a tool to score both noncoding and coding SNVs based on their potential to regulate the expression levels of nearby genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961785", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 679, "text": "Results We developed FIRE (Functional Inference of Regulators of Expression), a tool to score both noncoding and coding SNVs based on their potential to regulate the expression levels of nearby genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961785", "endSection": "abstract" } ] }, { "body": "Does TUC.338 inhibit colorectal cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27914101" ], "ideal_answer": [ "No. TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis. TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D015179", "http://www.disease-ontology.org/api/metadata/DOID:6981", "http://www.disease-ontology.org/api/metadata/DOID:9256", "https://meshb.nlm.nih.gov/record/ui?ui=D003123", "http://www.disease-ontology.org/api/metadata/DOID:0080199" ], "type": "yesno", "id": "5a6d23ccb750ff4455000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "TUC.338 promotes invasion and metastasis in colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914101", "endSection": "title" }, { "offsetInBeginSection": 441, "offsetInEndSection": 701, "text": "Until now, the role of TUC.338 in colorectal cancers remains undefined. This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914101", "endSection": "abstract" }, { "offsetInBeginSection": 1293, "offsetInEndSection": 1453, "text": " Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914101", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1453, "text": "Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914101", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 701, "text": "This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "TUC.338 promotes invasion and metastasis in colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914101", "endSection": "title" } ] }, { "body": "Describe mechanism of action of Napabucasin.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26899963", "http://www.ncbi.nlm.nih.gov/pubmed/29056905", "http://www.ncbi.nlm.nih.gov/pubmed/28573435", "http://www.ncbi.nlm.nih.gov/pubmed/28683005" ], "ideal_answer": [ "Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 (STAT3) pathway." ], "type": "summary", "id": "5a7345792dc08e987e000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28573435", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1166, "text": " The STAT3 transcription factor inhibitor, BBI608 (Napabucasin), strongly inhibited growth in almost all PDO cultures, suggesting that stemness programing is involved in organoid formation and/or growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683005", "endSection": "abstract" }, { "offsetInBeginSection": 1318, "offsetInEndSection": 1544, "text": " Diallyl trisulfide and napabucasin inhibit the signaling by the signal transducer and activator of transcription 3 (Stat3), potentially enhancing immune function by effects on T helper lymphocytes and promotion of apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056905", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 412, "text": "A small molecule, napabucasin (BBI608), recently have been identified with suppression of stemness-high cancer cells in a variety of cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26899963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28573435", "endSection": "abstract" } ] }, { "body": "Has ruxolitinib received FDA approval?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27796499" ], "ideal_answer": [ "Yes, ruxolitinib is FDA approved. In 2011 the oral JAK2 kinase inhibitor ruxolitinib became the first Food and Drug Administration (FDA)-approved drug for the treatment of myelofibrosis." ], "exact_answer": "yes", "type": "yesno", "id": "5a7626989e632bc066000001", "snippets": [ { "offsetInBeginSection": 441, "offsetInEndSection": 714, "text": "Testing for JAK2 mutations is now included in the World Health Organization (WHO) criteria for the diagnosis of MPN, and in 2011 the oral JAK2 kinase inhibitor ruxolitinib became the first Food and Drug Administration (FDA)-approved drug for the treatment of myelofibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27796499", "endSection": "abstract" } ] }, { "body": "Do origins of replication close to yeast centromeres fire early or late?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22589733", "http://www.ncbi.nlm.nih.gov/pubmed/23355306", "http://www.ncbi.nlm.nih.gov/pubmed/20808889", "http://www.ncbi.nlm.nih.gov/pubmed/8458255", "http://www.ncbi.nlm.nih.gov/pubmed/10408447", "http://www.ncbi.nlm.nih.gov/pubmed/2644653", "http://www.ncbi.nlm.nih.gov/pubmed/15795314" ], "ideal_answer": [ "Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome.", "In yeast each centromere is associated with a replication origin that is the first to fire on its respective chromosome.", "Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome. a neocentromere became the first to replicate and became associated with origin recognition complex (ORC) components. " ], "exact_answer": [ "Early" ], "type": "factoid", "id": "58eb99f3eda5a57672000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20808889", "endSection": "title" }, { "offsetInBeginSection": 613, "offsetInEndSection": 743, "text": "we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20808889", "endSection": "abstract" }, { "offsetInBeginSection": 881, "offsetInEndSection": 999, "text": "a neocentromere became the first to replicate and became associated with origin recognition complex (ORC) components. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20808889", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1397, "text": "Finally, analysis of centromere-associated DNA revealed a replication-dependent sequence pattern characteristic of constitutively active replication origins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20808889", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1074, "text": "We propose that by promoting replication fork integrity under these conditions Rad53 ensures centromere duplication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15795314", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1197, "text": " Two-dimensional gel analysis confirmed that mat1 is preferentially replicated by a centromere-distal origin(s).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408447", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 334, "text": "Mutations in two of these LCS (linear chromosome stability) genes had little or no effect on the loss rate of a circular YAC that had the same centromere and origin of replication as present on the linear YA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8458255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Lack of positional requirements for autonomously replicating sequence elements on artificial yeast chromosomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2644653", "endSection": "title" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1216, "text": "We find that terminal blocks of telomeric repeats are sufficient to be recognized as telomeres. Moreover, artificial chromosomes containing telomere-associated Y' sequences and telomeric ARSs were no more stable during both mitosis and meiosis than artificial chromosomes lacking terminal ARSs, indicating that yeast-specific blocks of telomeric sequences are the only cis-acting requirement for a functional telomere during both mitotic growth and meiosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2644653", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 571, "text": "Do centromeres ensure their early replication by promoting early activation of nearby origins, or have they migrated over evolutionary time to reside in early replicating regions?", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589733", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 1079, "text": "Because the activation time of individual origins is not an intrinsic property of S. cerevisiae origins, but is influenced by surrounding sequences, we sought to test the hypothesis that centromeres influence replication time by moving a centromere to a late replication domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589733", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 800, "text": "Do centromeres ensure their early replication by promoting early activation of nearby origins, or have they migrated over evolutionary time to reside in early replicating regions? In Candida albicans, a neocentromere contains an early firing origin, supporting the first hypothesis but not addressing whether the new origin is intrinsically early firing or whether the centromere influences replication time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22589733", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 732, "text": "cerevisiae replication are conserved: Centromeres replicate early, whereas telomeres replicate late, we found that replication origins both in L.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23355306", "endSection": "abstract" } ] }, { "body": "Is scuba diving safe during pregnancy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10087779", "http://www.ncbi.nlm.nih.gov/pubmed/19277936", "http://www.ncbi.nlm.nih.gov/pubmed/17000494", "http://www.ncbi.nlm.nih.gov/pubmed/8888455", "http://www.ncbi.nlm.nih.gov/pubmed/11777528", "http://www.ncbi.nlm.nih.gov/pubmed/12053898", "http://www.ncbi.nlm.nih.gov/pubmed/10416137", "http://www.ncbi.nlm.nih.gov/pubmed/12808399" ], "ideal_answer": [ "No, scuba diving should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D011247", "https://meshb.nlm.nih.gov/record/ui?ui=D004242" ], "type": "yesno", "id": "5a70de5199e2c3af26000005", "snippets": [ { "offsetInBeginSection": 842, "offsetInEndSection": 874, "text": "Scuba diving is contraindicated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19277936", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 907, "text": "Overall, the women did not conduct enough dives per pregnancy, therefore no significant correlation between diving and fetal abnormalities could be established. These data indicate women are increasingly observing the diving industry recommendation and refraining from diving while pregnant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17000494", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 715, "text": "Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12808399", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 678, "text": "Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11777528", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 679, "text": "Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12053898", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 544, "text": "The different international federations and the Undersea and Hyperbaric Medical Society advise against scuba diving for pregnant women or those planning a pregnancy, but no randomized trials or trials provide a solid scientific basis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10416137", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 649, "text": "Pregnant women are recommended not to dive, because the risk of birth defects seems to be greater among those who do, and there is a serious risk of fetal decompression disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10087779", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 543, "text": "The different international federations and the Undersea and Hyperbaric Medical Society advise against scuba diving for pregnant women or those planning a pregnancy, but no randomized trials or trials provide a solid scientific basis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10416137", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 678, "text": "Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12053898", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1349, "text": "Snorkeling can still be practiced during pregnancy, but scuba diving should be discontinued until after the birth period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8888455", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1350, "text": "Snorkeling can still be practiced during pregnancy, but scuba diving should be discontinued until after the birth period..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8888455", "endSection": "abstract" } ] }, { "body": "Does deflazacort have more side effects than prednisone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19488064" ], "ideal_answer": [ "Deflazacort produces fewer side effects than Prednisone in DMD patients." ], "exact_answer": "no", "type": "yesno", "id": "5a7726989e632bc06600000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19488064", "endSection": "abstract" } ] }, { "body": "Does echinacea increase anaphylaxis risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28731887", "http://www.ncbi.nlm.nih.gov/pubmed/9507713", "http://www.ncbi.nlm.nih.gov/pubmed/26593037", "http://www.ncbi.nlm.nih.gov/pubmed/11814277" ], "ideal_answer": [ "Yes, there is evidence that echinacea use is associated with anaphylaxis." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D020900", "https://meshb.nlm.nih.gov/record/ui?ui=D012306", "https://meshb.nlm.nih.gov/record/ui?ui=D000707" ], "type": "yesno", "id": "5a67a049b750ff4455000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 479, "text": "Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26593037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "BACKGROUND: Fifty percent of Australians use complementary and alternative medicines (other than vitamins) in any 12-month period, of which echinacea-containing products are increasingly popular. Recent reports have highlighted the risk of allergic reactions to complementary medicines in atopic patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11814277", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1280, "text": "Two patients suffered anaphylaxis and a third had an acute asthma attack 10 minutes after their first ever dose of echinacea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11814277", "endSection": "abstract" }, { "offsetInBeginSection": 1631, "offsetInEndSection": 1860, "text": "Fifty-one Australian adverse drug reports implicating echinacea were also reviewed. There were 26 cases suggestive of possible immunoglobulin E-mediated hypersensitivity (4 anaphylaxis, 12 acute asthma, 10 urticaria/angioedema). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11814277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "Echinacea-associated anaphylaxis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9507713", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "A woman with atopy experienced anaphylaxis after taking, among other dietary supplements, a commercial extract of echinacea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9507713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Risk of anaphylaxis in complementary and alternative medicine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28731887", "endSection": "title" }, { "offsetInBeginSection": 399, "offsetInEndSection": 676, "text": "Several culprits identified including Andrographis paniculata, Echinacea species, bee products, Ginkgo biloba and Ginseng are discussed here.SUMMARY: Knowing the factors that increase the risk of anaphylaxis allows reactions to be recognized, reported and further investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28731887", "endSection": "abstract" } ] }, { "body": "Are neurexins localized at pre-synapses?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28154140", "http://www.ncbi.nlm.nih.gov/pubmed/28643105", "http://www.ncbi.nlm.nih.gov/pubmed/27664583", "http://www.ncbi.nlm.nih.gov/pubmed/27725662" ], "ideal_answer": [ "Yes, neurexins are localized at pre-synapses." ], "exact_answer": "yes", "type": "yesno", "id": "5a8866958cb19eca6b000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Neurexins and neuroligins are two distinct families of single-pass transmembrane proteins localized at pre- and postsynapses, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27664583", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 87, "text": "presynaptic neurexins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27725662", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 307, "text": "best-characterized transsynaptic interactions are formed by presynaptic neurexins, which bind to diverse postsynaptic ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28154140", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 455, "text": "presynaptic neurexin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28643105", "endSection": "abstract" } ] }, { "body": "Is there any role of 5hmC in T-cell development and differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "http://www.ncbi.nlm.nih.gov/pubmed/27346350" ], "ideal_answer": [ "Yes. 5hmC is enriched in the gene body of highly expressed genes at all different stages of T-cell development in the thymus and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, 5hmC is enriched in active thymus-specific enhancers and genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0030217", "http://amigo.geneontology.org/amigo/term/GO:0045580", "http://amigo.geneontology.org/amigo/term/GO:0045589" ], "type": "yesno", "id": "5a6d0727b750ff445500002b", "snippets": [ { "offsetInBeginSection": 173, "offsetInEndSection": 927, "text": "We have mapped 5-hydroxymethylcytosine (5hmC) at different stages of T-cell development in the thymus and T-cell differentiation in the periphery. We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect. Our data constitute a valuable resource that will facilitate detailed analysis of the role of 5hmC in T-cell development and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 486, "text": "We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 785, "text": "Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 486, "text": "We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071199", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 488, "text": "Here, we report early and widespread 5mC/5hmC remodeling during human CD4(+) T\u00a0cell differentiation ex\u00a0vivo at genes and cell-specific enhancers with known T\u00a0cell function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27346350", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1129, "text": "Our results support 5hmC-mediated DNA de-methylation as a key component of CD4(+) T\u00a0cell biology in humans, with important implications for gene regulation and lineage commitment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27346350", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 311, "text": "5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T\u00a0cell malignancies and autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27346350", "endSection": "abstract" } ] }, { "body": "Which are the properties of mammalian GA-sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8855950", "http://www.ncbi.nlm.nih.gov/pubmed/10037452", "http://www.ncbi.nlm.nih.gov/pubmed/11095670", "http://www.ncbi.nlm.nih.gov/pubmed/22342253", "http://www.ncbi.nlm.nih.gov/pubmed/9545369", "http://www.ncbi.nlm.nih.gov/pubmed/19043592", "http://www.ncbi.nlm.nih.gov/pubmed/273896", "http://www.ncbi.nlm.nih.gov/pubmed/19270754", "http://www.ncbi.nlm.nih.gov/pubmed/9490799", "http://www.ncbi.nlm.nih.gov/pubmed/9607333", "http://www.ncbi.nlm.nih.gov/pubmed/8411173" ], "ideal_answer": [ " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences (combined<0.5%), all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum.", "GA-sequences are DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300. All pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins. Although this could have made them less subject to natural selection, they contained many [corrected] times fewer point mutations than one should expect from the genome at large.", " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300 [b].", "GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome.", "The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins. The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's . Hence, guanine and thymine share significant properties regarding complementarity to adenine, while the TA and GA sequences can stack in at least two mutually compatible ways within the DNA duplexes analyzed here. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly-segment. With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences , all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. ", "The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences (combined<0.5%), all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment", " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way", " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome.", " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300 [b]. Alternating polypurine d(GA)n, sequences exhibit a considerable polymorphism Hence, guanine and thymine share significant properties regarding complementarity to adenine, while the TA and GA sequences can stack in at least two mutually compatible ways within the DNA duplexes analyzed here" ], "type": "summary", "id": "5a43a581966455904c00000a", "snippets": [ { "offsetInBeginSection": 124, "offsetInEndSection": 428, "text": " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22342253", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 363, "text": " most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270754", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 471, "text": "The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 817, "text": "The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300 [b]. With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences (combined<0.5%), all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043592", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 183, "text": "Here we report that alpha d(GA) x d(GA) sequences form an antiparallel stranded duplex DNA at neutral pH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9607333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Alternating polypurine d(GA)n, sequences exhibit a considerable polymorphism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9607333", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 994, "text": "Hence, guanine and thymine share significant properties regarding complementarity to adenine, while the TA and GA sequences can stack in at least two mutually compatible ways within the DNA duplexes analyzed here", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490799", "endSection": "abstract" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1247, "text": "Implications of these results for an understanding of the molecular principles behind the conformational flexibility of alternating d(GA.TC)n sequences are discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8411173", "endSection": "abstract" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1292, "text": "The functions of pure GA-sequences are not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043592", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 364, "text": "Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270754", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 425, "text": "Depending on the conditions, d(GA)n DNA sequences can form antiparallel-and parallel-stranded homoduplexes, multistranded complexes, and ordered single-stranded conformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8855950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1) the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270754", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 567, "text": "This observation demonstrates that homoduplexes of alternating GA and TA sequences can co-exist in a single DNA molecule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490799", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 615, "text": "Duplexes of the dodeca-satellite purine-rich strand, carrying tandem 5'-GA:GA-3' mismatches, are as stable as equivalent fully Watson-Crick duplexes containing tandem 5'-TA:TA-3' Watson-Crick pairs in place of the non-Watson-Crick G.A pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9545369", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 712, "text": "With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences (combined <0.5%), all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "To discover safe and effective topical skin-lightening agents, we have evaluated alkyl esters of the natural product gentisic acid (GA), which is related to our lead compound methyl gentisate (MG), and four putative tyrosinase inhibitors, utilizing mammalian melanocyte cell cultures and cell-free extracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10037452", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 617, "text": "Physicochemical characterization of the new structures and model building are consistent with, in the case of d(TC)n-d(GA)n, a tetra-stranded complex forming by the addition of d(GA)n to the remaining space in the major groove of the triple-stranded complex d(TC)n-d(GA)n-d(CT)n. A possible role for tetra-stranded complexes in chromosome condensation is suggested by the natural occurrence of repeating sequence pyrimidine-purine DNAs and the properties of condensed chromosomes.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/273896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Properties and distribution of pure GA-sequences of mammalian genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043592", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences').", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19043592", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 472, "text": "The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Outline of a genome navigation system based on the properties of GA-sequences and their flanks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19270754", "endSection": "title" }, { "offsetInBeginSection": 781, "offsetInEndSection": 893, "text": "The potential contribution of the structural properties of d(GA x TC)(n) sequences to this effect is discussed..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11095670", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 995, "text": "Hence, guanine and thymine share significant properties regarding complementarity to adenine, while the TA and GA sequences can stack in at least two mutually compatible ways within the DNA duplexes analyzed here.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9490799", "endSection": "abstract" } ] }, { "body": "What is the main focus of the CVE R/Bioconductor package?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28545463" ], "ideal_answer": [ "The CVE package allows interactive variant prioritisation to expedite the analysis of cancer sequencing studies.", "CVE is an R package for interactive variant prioritisation in precision oncology. Leveraging Oncotator and the Drug Gene Interaction Database, CVE offers exploration of variants within single or multiple tumour exomes to identify drivers, resistance mechanisms and to assess druggability.", "interactive variant prioritisation" ], "type": "summary", "id": "5a6e3299b750ff4455000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "CVE: an R package for interactive variant prioritisation in precision oncology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28545463", "endSection": "title" }, { "offsetInBeginSection": 242, "offsetInEndSection": 448, "text": "Leveraging Oncotator and the Drug Gene Interaction Database, CVE offers exploration of variants within single or multiple tumour exomes to identify drivers, resistance mechanisms and to assess druggability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28545463", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 766, "text": "The CVE package allows interactive variant prioritisation to expedite the analysis of cancer sequencing studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28545463", "endSection": "abstract" } ] }, { "body": "Are there ultraconserved genomic regions in the budding yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028909" ], "ideal_answer": [ "Yes. In addition to some fundamental biological functions, ultraconserved genomic regions play an important role in the adaptation of S. cerevisiae to the acidic environment." ], "exact_answer": "yes", "type": "yesno", "id": "5a6d217eb750ff4455000034", "snippets": [ { "offsetInBeginSection": 341, "offsetInEndSection": 1144, "text": "Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.Results: Our results indicate that, in addition to some fundamental biological functions, the UCSs play an important role in the adaptation of S. cerevisiae to the acidic environment, which is backed up by the previous observation. Besides that, we also find the highly unchanged genes (HUGs) are enriched in some other pathways, such as the nutrient-sensitive signaling pathway. To facilitate the investigation of unique UCSs, the UCSC Genome Browser was utilized to visualize the chromosomal position and related annotations of UCSs in S. cerevisiae genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 584, "text": "Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "abstract" } ] }, { "body": "Is davunetide being considered for the treatment of progressive supranuclear palsy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22347799" ], "ideal_answer": [ "Yes, Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients." ], "exact_answer": "yes", "type": "yesno", "id": "5a7d5033faa1ab7d2e000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22347799", "endSection": "title" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1366, "text": "Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22347799", "endSection": "abstract" } ] }, { "body": "What is the origin of XUT transcripts in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21697827", "http://www.ncbi.nlm.nih.gov/pubmed/29114019", "http://www.ncbi.nlm.nih.gov/pubmed/26805575" ], "ideal_answer": [ "XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast", "XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast.", "Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. 3' single-stranded (3'-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses, and double-stranded (ds)RNA mapping revealed that 3'-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated, locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anticomplementary transcripts protects cryptic intergenic lncRNAs from NMD." ], "concepts": [ "http://www.uniprot.org/uniprot/RENT2_HUMAN", "http://amigo.geneontology.org/amigo/term/GO:2000623", "https://meshb.nlm.nih.gov/record/ui?ui=D012441", "https://meshb.nlm.nih.gov/record/ui?ui=D015003", "http://amigo.geneontology.org/amigo/term/GO:0000184", "https://meshb.nlm.nih.gov/record/ui?ui=D059365", "http://www.uniprot.org/uniprot/RENT1_HUMAN", "http://www.uniprot.org/uniprot/REN3B_HUMAN", "http://www.uniprot.org/uniprot/REN3A_HUMAN", "http://amigo.geneontology.org/amigo/term/GO:2000622" ], "type": "summary", "id": "5a855585faa1ab7d2e000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697827", "endSection": "title" }, { "offsetInBeginSection": 706, "offsetInEndSection": 888, "text": "Here, using strand-specific RNA sequencing (RNA-seq), we identify a novel class of 1,658 Xrn1-sensitive unstable transcripts (XUTs) in which 66% are antisense to open reading frames.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697827", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1132, "text": "The majority of XUTs strongly accumulate in lithium-containing media, indicating that they might have a role in adaptive responses to changes in growth conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697827", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1640, "text": "Furthermore, abolishing H3K4me3 triggers the silencing of other genes with antisense XUTs, supporting a model in which H3K4me3 antagonizes antisense ncRNA repressive activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697827", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 413, "text": "Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3' single-stranded (3'-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26805575", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 670, "text": "Ribosome profiling showed that XUT are translated, locking them for NMD activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26805575", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 810, "text": "Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a\u00a0critical step for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26805575", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 779, "text": "Strikingly, antisense transcription was detected for most protein-coding genes, correlating with low sense transcription, especially when overlapping the mRNA start site. RNA profiling revealed that the resulting aslncRNAs mainly correspond to cryptic Xrn1/Exo2-sensitive transcripts (XUTs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29114019", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1337, "text": "Finally, we showed that asXUTs are controlled by the histone chaperone Spt6 and respond to meiosis induction, in both cases anti-correlating with levels of the paired-sense mRNAs, supporting physiological significance to antisense-mediated gene attenuation. Our work highlights that antisense transcription is much more extended than anticipated and might constitute an additional non-promoter determinant of gene regulation complexity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29114019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1127, "text": "Antisense long non-coding (aslnc)RNAs represent a\u00a0substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3' single-stranded (3'-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses, and double-stranded (ds)RNA mapping revealed that 3'-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated, locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a\u00a0critical step for degradation. Indeed, expression of anticomplementary transcripts protects cryptic intergenic lncRNAs from NMD. Our results indicate that aslncRNAs form dsRNA that are only translated\u00a0and targeted to NMD if dissociated by Mtr4 and Dbp2. We propose that NMD buffers genome expression by discarding pervasive regulatory transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26805575", "endSection": "abstract" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1338, "text": "Notably, RNAPII chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) analysis of Xrn1-deficient strains revealed a significant decrease of RNAPII occupancy over 273 genes with antisense XUTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697827", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 285, "text": "Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26805575", "endSection": "abstract" } ] }, { "body": "How many genes constitute the DosR regulon, controlled by the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22833514", "http://www.ncbi.nlm.nih.gov/pubmed/21653552", "http://www.ncbi.nlm.nih.gov/pubmed/19553548", "http://www.ncbi.nlm.nih.gov/pubmed/23651670", "http://www.ncbi.nlm.nih.gov/pubmed/18294384", "http://www.ncbi.nlm.nih.gov/pubmed/17502400", "http://www.ncbi.nlm.nih.gov/pubmed/22759512" ], "ideal_answer": [ "The Mycobacterium dormancy survival regulator (DosR) regulon is composed of 48 co-regulated genes.", "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. DosR/DevR of M. tuberculosis is a two component dormancy survival response regulator which induces the expression of 48 genes. ", "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence.", "The dormancy survival regulator regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence. The two component sensor/regulator dosRS is a major mediator in the transcriptional response of M. tuberculosis to hypoxia and controls a regulon of approximately 50 genes that are induced under this condition. ", "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions.", "The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence. During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions." ], "exact_answer": [ "48 genes" ], "type": "factoid", "id": "58edf567eda5a57672000011", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 431, "text": "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651670", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 438, "text": "The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22833514", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 227, "text": " DosR/DevR of M. tuberculosis is a two component dormancy survival response regulator which induces the expression of 48 genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22759512", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 923, "text": "The functional importance of tandem arrangement was established by analyzing promoter variants harboring Dev boxes with altered spacing. Conserved sequence logos were generated from 47 binding sequences which included 24 newly discovered Dev boxes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21653552", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 352, "text": " The two component sensor/regulator dosRS is a major mediator in the transcriptional response of M. tuberculosis to hypoxia and controls a regulon of approximately 50 genes that are induced under this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18294384", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 720, "text": "In silico analysis of the DosR regulon in BCG and M. tuberculosis showed at least 97% amino acid sequence homology, with 41 out of 48 genes being identical.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17502400", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 226, "text": "DosR/DevR of M. tuberculosis is a two component dormancy survival response regulator which induces the expression of 48 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22759512", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 226, "text": "tuberculosis is a two component dormancy survival response regulator which induces the expression of 48 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22759512", "endSection": "abstract" } ] }, { "body": "Is autophagy modulated in a circadian fashion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28514207", "http://www.ncbi.nlm.nih.gov/pubmed/28721811", "http://www.ncbi.nlm.nih.gov/pubmed/28196106", "http://www.ncbi.nlm.nih.gov/pubmed/29113329", "http://www.ncbi.nlm.nih.gov/pubmed/28865774", "http://www.ncbi.nlm.nih.gov/pubmed/27171500" ], "ideal_answer": [ "Yes, metabolic pathways, bile acid synthesis, and autophagic and immune/inflammatory processes are driven by the biological clock." ], "exact_answer": "yes", "type": "yesno", "id": "5a87fd0561bb38fb24000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28196106", "endSection": "title" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1593, "text": " Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28196106", "endSection": "abstract" }, { "offsetInBeginSection": 1843, "offsetInEndSection": 1930, "text": "the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28721811", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 402, "text": "Metabolic pathways, bile acid synthesis, and autophagic and immune/inflammatory processes are driven by the biological clock. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28865774", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1007, "text": "our findings suggest that the clock geneBmal1is a positive regulator of autophagy through the mTOR signaling pathway and protects cardiomyocytes against high-glucose toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Autophagy is a highly conserved intracellular degradation system, and recently was shown to display circadian rhythms in mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27171500", "endSection": "abstract" } ] }, { "body": "Is Drk essential for anesthesia-resistant memory (ARM) in Drosophila?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28973902" ], "ideal_answer": [ "Yes. Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons in Drosophila." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004331", "https://meshb.nlm.nih.gov/record/ui?ui=D004330", "http://amigo.geneontology.org/amigo/term/GO:0007615" ], "type": "yesno", "id": "5a7607f683b0d9ea66000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 519, "text": "Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory inDrosophilaremain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, theDrosophilaortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28973902", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 523, "text": "We present evidence that Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28973902", "endSection": "abstract" } ] }, { "body": "What is oclacitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24495176" ], "ideal_answer": [ "Oclacitinib (APOQUEL(\u00ae)) is a Janus kinase inhibitor with activity against cytokines involved in allergy. It is a potent inhibitor of JAK1. It effectively controls clinical signs associated with allergic skin disease in dogs." ], "type": "summary", "id": "5a76122383b0d9ea6600001c", "snippets": [ { "offsetInBeginSection": 123, "offsetInEndSection": 295, "text": "The objective of this study was to determine whether the novel JAK inhibitor oclacitinib could reduce the activity of cytokines implicated in canine allergic skin disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24495176", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 1430, "text": "Oclacitinib inhibited JAK family members by 50% at concentrations (IC50 's) ranging from 10 to 99 nm and did not inhibit a panel of 38 non-JAK kinases (IC50 's>1000 nM). Oclacitinib was most potent at inhibiting JAK1 (IC50 = 10 nM). Oclacitinib also inhibited the function of JAK1-dependent cytokines involved in allergy and inflammation (IL-2, IL-4, IL-6, and IL-13) as well as pruritus (IL-31) at IC50 's ranging from 36 to 249 nM. Oclacitinib had minimal effects on cytokines that did not activate the JAK1 enzyme in cells (erythropoietin, granulocyte/macrophage colony-stimulating factor, IL-12, IL-23; IC50 's>1000 nM). These results demonstrate that oclacitinib is a targeted therapy that selectively inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus and suggests these are the mechanisms by which oclacitinib effectively controls clinical signs associated with allergic skin disease in dogs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24495176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Oclacitinib (APOQUEL(\u00ae)) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24495176", "endSection": "title" } ] }, { "body": "Are TAD boundaries in Drosophila depleted in highly-expressed genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26748519", "http://www.ncbi.nlm.nih.gov/pubmed/26030525", "http://www.ncbi.nlm.nih.gov/pubmed/25959774", "http://www.ncbi.nlm.nih.gov/pubmed/25367294", "http://www.ncbi.nlm.nih.gov/pubmed/26431028", "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "http://www.ncbi.nlm.nih.gov/pubmed/26518482" ], "ideal_answer": [ "Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes.", "Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them. Drosophila inter-TADs harbor active chromatin and constitutively transcribed genes. We conclude that epigenetic modifications, gene density, and transcriptional activity combine to shape the local packing of the A. thaliana nuclear genome. ", "Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them." ], "exact_answer": "no", "type": "yesno", "id": "58ee1cafeda5a57672000014", "snippets": [ { "offsetInBeginSection": 756, "offsetInEndSection": 888, "text": "Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26748519", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 360, "text": "In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26518482", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 990, "text": "Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26518482", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1331, "text": "The insulator-like, TAD-boundary-like, and TAD-interior-like regions are each enriched for distinct epigenetic marks and are each correlated with different gene expression levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25367294", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1488, "text": "We conclude that epigenetic modifications, gene density, and transcriptional activity combine to shape the local packing of the A. thaliana nuclear genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25367294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959774", "endSection": "title" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1143, "text": "Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26030525", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 692, "text": "Ectopically expressed roX1 and roX2 RNAs target HAS on the X chromosome in trans and, via spatial proximity, induce spreading of the MSL complex in cis, leading to increased expression of neighboring autosomal genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26431028", "endSection": "abstract" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1428, "text": "Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26518482", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 989, "text": "However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26518482", "endSection": "abstract" } ] }, { "body": "List the two most important hematological features of the Evans syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12554529", "http://www.ncbi.nlm.nih.gov/pubmed/28937520", "http://www.ncbi.nlm.nih.gov/pubmed/28654461", "http://www.ncbi.nlm.nih.gov/pubmed/28054583", "http://www.ncbi.nlm.nih.gov/pubmed/28267088", "http://www.ncbi.nlm.nih.gov/pubmed/11339180", "http://www.ncbi.nlm.nih.gov/pubmed/20031296", "http://www.ncbi.nlm.nih.gov/pubmed/19055865", "http://www.ncbi.nlm.nih.gov/pubmed/27821514", "http://www.ncbi.nlm.nih.gov/pubmed/28878866", "http://www.ncbi.nlm.nih.gov/pubmed/21088621", "http://www.ncbi.nlm.nih.gov/pubmed/22796025", "http://www.ncbi.nlm.nih.gov/pubmed/28680366", "http://www.ncbi.nlm.nih.gov/pubmed/29163997" ], "ideal_answer": [ "Evans syndrome is a rare autoimmune disorder, which is characterized by immune thrombocytopenia and autoimmune hemolytic anemia." ], "exact_answer": [ [ "immune thrombocytopenia" ], [ "autoimmune hemolytic anemia" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8931" ], "type": "list", "id": "5a76196faacfb9cd4c000001", "snippets": [ { "offsetInBeginSection": 666, "offsetInEndSection": 782, "text": "Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count<100,000/mm3) and AIHA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27821514", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 908, "text": "Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28054583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "BACKGROUND: Autoimmune cytopenias are characterized by immune-mediated destruction of hematopoietic cell lines with immune thrombocytopenia (ITP) affecting platelets and Evans syndrome (ES) affecting platelets and red blood cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28267088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Primary Evans syndrome (ES) is defined by the concurrent or sequential occurrence of immune thrombocytopenia and autoimmune hemolytic anemia in the absence of an underlying etiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28654461", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 256, "text": "Evans syndrome (ES) is a rare autoimmune disorder, which is characterized by immune thrombocytopenia and autoimmune hemolytic anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28878866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND: Evans syndrome (ES) is a rare immune disorder in children, manifested by simultaneous or sequential autoimmune cytopenias (ACs) of unknown cause and having a chronic course with periods of exacerbation and remission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28937520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Evans syndrome (ES) is a rare autoimmune disorder whose exact pathophysiology is unknown. It is characterized by the simultaneous or subsequent development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29163997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Evans' syndrome is an unusual illness of autoimmune etiology, characterized by thrombocytopenia and hemolytic anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11339180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Evans syndrome is an uncommon condition characterised by simultaneous or sequential development of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of a known underlying aetiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19055865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Evans' syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia purpura and autoimmune hemolytic anemia with a positive direct antiglobulin test in the absence of known underlying etiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22796025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Evans syndrome is a very rare hematologic autoimmune disease, characterized by a direct Coombs' positive hemolytic anemia and immune thrombocytopenic purpura without a known underlying etiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21088621", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 355, "text": "Evans syndrome usually is complicated by hemolytic or thrombocytopenic symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21088621", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 718, "text": "The selection criteria were Evans' syndrome in pregnancy; autoimmune haemolytic anaemia; immune thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20031296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "Evans' syndrome is an unusual illness of autoimmune etiology, characterized by thrombocytopenia and hemolytic anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11339180", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 422, "text": "Evans syndrome refers to a hematological autoimmune disorder with autoimmune hemolytic anemia accompanied by immune thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12554529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "Evans syndrome is a very rare hematologic autoimmune disease, characterized by a direct Coombs' positive hemolytic anemia and immune thrombocytopenic purpura without a known underlying etiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21088621", "endSection": "abstract" } ] }, { "body": "Is there increased recombination rate in human regulatory domains?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29058599" ], "ideal_answer": [ "No. There is evidence of significantly reduced recombination rate compared to matched control regions at human regulatory domains." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0006310", "https://meshb.nlm.nih.gov/record/ui?ui=D050436", "https://meshb.nlm.nih.gov/record/ui?ui=D011995" ], "type": "yesno", "id": "5a774ce1faa1ab7d2e000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Evidence of reduced recombination rate in human regulatory domains.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058599", "endSection": "title" }, { "offsetInBeginSection": 337, "offsetInEndSection": 1664, "text": "We study the relationship between recombination rate and gene regulatory domains, defined by a gene and its linked control elements. We define these links using expression quantitative trait loci (eQTLs), methylation quantitative trait loci (meQTLs), chromatin conformation from publicly available datasets\u00a0(Hi-C and ChIA-PET), and correlated activity links that we infer across cell types. Each link type shows a \"recombination rate\u00a0valley\" of significantly reduced recombination rate compared to matched control regions. This recombination rate\u00a0valley is most pronounced for gene regulatory domains of early embryonic development genes, housekeeping genes, and constitutive regulatory elements, which are known to show increased evolutionary constraint across species. Recombination rate\u00a0valleys show increased DNA methylation, reduced doublestranded break initiation, and increased repair efficiency, specifically in the lineage leading to the germ line. Moreover, by using only the overlap of functional links and DNA methylation in germ cells, we are able to predict the recombination rate with high accuracy.CONCLUSIONS: Our results suggest the existence of a recombination rate valley at regulatory domains and provide a potential molecular mechanism to interpret the interplay between genetic and epigenetic variations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058599", "endSection": "abstract" } ] }, { "body": "Is enzastaurin effective treatment of glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17620423", "http://www.ncbi.nlm.nih.gov/pubmed/26643807", "http://www.ncbi.nlm.nih.gov/pubmed/27052640", "http://www.ncbi.nlm.nih.gov/pubmed/21035151", "http://www.ncbi.nlm.nih.gov/pubmed/25398844", "http://www.ncbi.nlm.nih.gov/pubmed/23911595", "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "http://www.ncbi.nlm.nih.gov/pubmed/26692525", "http://www.ncbi.nlm.nih.gov/pubmed/21896554", "http://www.ncbi.nlm.nih.gov/pubmed/20044633", "http://www.ncbi.nlm.nih.gov/pubmed/20150385" ], "ideal_answer": [ "No. Enzastaurin does not improve prognosis of glioblastoma patients." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D005909", "http://www.biosemantics.org/jochem#4240085", "https://meshb.nlm.nih.gov/record/ui?ui=D016896" ], "type": "yesno", "id": "5a7612b483b0d9ea6600001d", "snippets": [ { "offsetInBeginSection": 542, "offsetInEndSection": 1014, "text": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "endSection": "abstract" }, { "offsetInBeginSection": 1744, "offsetInEndSection": 1929, "text": "Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26643807", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 840, "text": "So far, inhibition of angiogenesis by compounds such as bevacizumab, cediranib, enzastaurin or cilengitide as well as alternative dosing schedules of temozolomide did not prolong survival, neither at primary diagnosis nor at recurrent disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27052640", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 927, "text": "Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398844", "endSection": "abstract" }, { "offsetInBeginSection": 1489, "offsetInEndSection": 1551, "text": "CONCLUSIONS: PFS-6 missed the primary planned outcome of 55%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23911595", "endSection": "abstract" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1403, "text": "OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotinib and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896554", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1379, "text": "More recently, antiangiogenic agents including enzastaurin, cediranib, bevacizumab, and others that target mainly the VEGF pathway, have been evaluated in this highly angiogenic disease. Among them, only bevacizumab has been associated with clear anti-tumor activity, although the lack of control studies limits the impact of the results to date.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035151", "endSection": "abstract" }, { "offsetInBeginSection": 1516, "offsetInEndSection": 1684, "text": "Enzastaurin has anti-glioma activity in patients with recurrent high-grade glioma, but does not appear to have enough single-agent activity to be useful as monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20150385", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1525, "text": "Several signal transduction inhibitors have been examined in preclinical and clinical malignant glioma trials, including antiangiogenic agents (bevacizumab, enzastaurin), and inhibitors of epidermal growth factor receptor tyrosine kinase (gefitinib and erlotinib), mammalian target of rapamycin (temsirolimus, everolimus) and integrin (cilengitide). Although preliminary clinical results of the use of targeted agents have not translated into significantly better survival, more recent phase II trials are exploring the combination of multitargeted drugs with cytotoxic chemotherapy and radiotherapy in order to overcome the resistance of tumors to single-agent targeted therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20044633", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 1298, "text": "Several drugs have been tested, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib and erlotinib), mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus), and vascular endothelial growth factor receptor (VEGFR), protein kinase C-beta, and other angiogenesis pathways inhibitors (vatalanib, bevacizumab, and enzastaurin). Although preliminary efficacy results of most trials in recurrent disease have fallen short on expectations, substantial advances have been achieved by associated translational research. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17620423", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 842, "text": "So far, inhibition of angiogenesis by compounds such as bevacizumab, cediranib, enzastaurin or cilengitide as well as alternative dosing schedules of temozolomide did not prolong survival, neither at primary diagnosis nor at recurrent disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27052640", "endSection": "abstract" } ] }, { "body": "Which yeast nucleosomes are preferentially marked by H2A.Z?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26789756", "http://www.ncbi.nlm.nih.gov/pubmed/22393239", "http://www.ncbi.nlm.nih.gov/pubmed/19246569", "http://www.ncbi.nlm.nih.gov/pubmed/16248679", "http://www.ncbi.nlm.nih.gov/pubmed/28951178", "http://www.ncbi.nlm.nih.gov/pubmed/27992255", "http://www.ncbi.nlm.nih.gov/pubmed/24613878", "http://www.ncbi.nlm.nih.gov/pubmed/22821566" ], "ideal_answer": [ "Yeast nucleosomes containing histone variant H2A.Z (Htz1p in yeast) are primarily composed of H4 K12ac and H3 K4me3.", "H2A.Z represses gene expression by establishing low gene accessibility at +1 nucleosome and maintaining high gene accessibility at -1 nucleosome. \u0397igh measures of gene responsiveness correlate with the H2A.Z-associated closed +1 nucleosome structure.", "The H2A and H2A.Z nucleosomes have different sequence preferences. The shifted peaks coincide with DNA regions interacting with the histone loops. Deposition of the histone variant H2A.Z at gene bodies regulates transcription by modifying chromatin accessibility in plants. We showed that H2A.Z preferentially associated with H3K4me3 at promoters, while it was found with H3K27me3 at enhancers, and that H2A.Z deposition negatively correlated with gene expression. In addition, we demonstrated that H2A.Z represses gene expression by establishing low gene accessibility at\u00a0+1 nucleosome\u00a0and maintaining high gene accessibility at -1 nucleosome. We further showed that the high measures of gene responsiveness correlate with the H2A.Z-associated closed\u00a0+1 nucleosome structure." ], "concepts": [ "http://www.uniprot.org/uniprot/H2AZ_PONAB", "http://www.uniprot.org/uniprot/H2AZ_RAT", "https://meshb.nlm.nih.gov/record/ui?ui=D009707", "http://amigo.geneontology.org/amigo/term/GO:0034728", "http://www.uniprot.org/uniprot/H2AZ_MOUSE", "http://www.uniprot.org/uniprot/H2AZ_ONCMY", "http://www.uniprot.org/uniprot/H2AZ_SHEEP" ], "type": "summary", "id": "5a82fc89faa1ab7d2e000028", "snippets": [ { "offsetInBeginSection": 1210, "offsetInEndSection": 1356, "text": "The H2A and H2A.Z nucleosomes have different sequence preferences. The shifted peaks coincide with DNA regions interacting with the histone loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27992255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Deposition of the histone variant H2A.Z at gene bodies regulates transcription by modifying chromatin accessibility in plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28951178", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 638, "text": "We showed that H2A.Z preferentially associated with H3K4me3 at promoters, while it was found with H3K27me3 at enhancers, and that H2A.Z deposition negatively correlated with gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28951178", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 950, "text": "In addition, we demonstrated that H2A.Z represses gene expression by establishing low gene accessibility at\u00a0+1 nucleosome\u00a0and maintaining high gene accessibility at -1 nucleosome. We further showed that the high measures of gene responsiveness correlate with the H2A.Z-associated closed\u00a0+1 nucleosome structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28951178", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 300, "text": "In particular, replacement of the canonical H2A histone with the variants macroH2A and H2A.Z has been shown to affect DNA accessibility and nucleosome stability;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26789756", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 395, "text": "Using genome-wide nucleosome maps and histone variant occupancy in the mouse liver, we show that the majority of genes were associated with a single prominent H2A.Z containing nucleosome in their promoter region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Proximity of H2A.Z containing nucleosome to the transcription start site influences gene expression levels in the mammalian liver and brain", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821566", "endSection": "title" }, { "offsetInBeginSection": 479, "offsetInEndSection": 632, "text": "The genes with no detectable H2A.Z showed lowest expression level, whereas H2A.Z was positioned closer to the TSS of genes with higher expression levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821566", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 857, "text": "The proximity of histone variant H2A.Z, but not H3.3 to the TSS, over seven consecutive nucleosomes, was correlated with expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821566", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1117, "text": " Our results suggest that gene expression levels in vivo are determined by accessibility of the TSS and proximity of H2A.Z.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22821566", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1169, "text": "We also find that human H2A.Z nucleosomes protect only approximately 120 bp of DNA from MNase digestion and exhibit specific sequence preferences, suggesting a novel mechanism of nucleosome organization for the H2A.Z variant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19246569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16248679", "endSection": "title" }, { "offsetInBeginSection": 539, "offsetInEndSection": 763, "text": "We have identified 4,862 small regions--typically one or two nucleosomes wide--decorated with H2A.Z. Those \"Z loci\" are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16248679", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1191, "text": "Genome-wide profiling of Anp32e revealed a remarkable co-occupancy between Anp32e and H2A.Z. Cells overexpressing Anp32e displayed a strong global H2A.Z loss at the +1 nucleosomes, whereas cells depleted of Anp32e displayed a moderate global H2A.Z increase at the +1 nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24613878", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1419, "text": "This suggests that Anp32e may help to resolve the non-nucleosomal H2A.Z aggregates and also facilitate the removal of H2A.Z at the +1 nucleosomes, and the latter may help RNA polymerase II to pass the first nucleosomal barrier.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24613878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 747, "text": "Although distinct epigenetic marks correlate with different chromatin states, how they are integrated within single nucleosomes to generate combinatorial signals remains largely unknown. We report the successful implementation of single molecule tools constituting fluorescence correlation spectroscopy (FCS), pulse interleave excitation-based F\u00f6rster resonance energy transfer (PIE-FRET) and fluorescence lifetime imaging-based FRET (FLIM-FRET) to elucidate the composition of single nucleosomes containing histone variant H2A.Z (Htz1p in yeast) in vitro and in vivo. We demonstrate that yeast nucleosomes containing Htz1p are primarily composed of H4 K12ac and H3 K4me3 but not H3 K36me3 and that these patterns are conserved in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22393239", "endSection": "abstract" } ] }, { "body": "Is dasatinib effective for treatment of glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21153679", "http://www.ncbi.nlm.nih.gov/pubmed/23090987", "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "http://www.ncbi.nlm.nih.gov/pubmed/25758746" ], "ideal_answer": [ "No, dasatinib is ineffective for treatment of glioblastoma and is associated with significant toxicity." ], "exact_answer": "no", "concepts": [ "http://www.biosemantics.org/jochem#4244012", "http://www.biosemantics.org/jochem#4274027", "https://meshb.nlm.nih.gov/record/ui?ui=D000069439", "https://meshb.nlm.nih.gov/record/ui?ui=D005909", "https://meshb.nlm.nih.gov/record/ui?ui=D016896" ], "type": "yesno", "id": "5a760ed883b0d9ea66000019", "snippets": [ { "offsetInBeginSection": 542, "offsetInEndSection": 1013, "text": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1656, "text": "CONCLUSIONS: Intraparticipant dose escalation was feasible, but dasatinib was ineffective in recurrent GBM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25758746", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1372, "text": "Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2-1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090987", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1488, "text": "Dasatinib in conjunction with bevacizumab does not appear to have activity in patients with recurrent, heavily pretreated GBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21153679", "endSection": "abstract" } ] }, { "body": "Which algorithm is available for computing minimal absent words using external memory?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28407038" ], "ideal_answer": [ "emMAW", "emMAW is the first external-memory algorithm for computing minimal absent words. A free open-source implementation of this algorithm is available. This implementation requires less than 3\u2009h on a standard workstation to process the full human genome when as little as 1\u2009GB of RAM is made available." ], "exact_answer": [ "emMAW" ], "type": "factoid", "id": "5a6a3335b750ff4455000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "emMAW: computing minimal absent words in external memory.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407038", "endSection": "title" }, { "offsetInBeginSection": 651, "offsetInEndSection": 1067, "text": "We present emMAW, the first external-memory algorithm for computing minimal absent words. A free open-source implementation of our algorithm is made available. This allows for computation of minimal absent words on far bigger data sets than was previously possible. Our implementation requires less than 3\u2009h on a standard workstation to process the full human genome when as little as 1\u2009GB of RAM is made available. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407038", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 720, "text": "We present emMAW, the first external-memory algorithm for computing minimal absent words.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407038", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 741, "text": "We present emMAW, the first external-memory algorithm for computing minimal absent words.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407038", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 742, "text": "Results We present emMAW, the first external-memory algorithm for computing minimal absent words.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407038", "endSection": "abstract" } ] }, { "body": "Has IVIG been tested in clinical trials for the treatment of Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24760112" ], "ideal_answer": [ "Yes, IVIG has been tested in clinical trials for the treatment of Alzheimer's disease." ], "exact_answer": "yes", "type": "yesno", "id": "5a7d54adfaa1ab7d2e000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Clinical trials of intravenous immunoglobulin for Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760112", "endSection": "title" }, { "offsetInBeginSection": 176, "offsetInEndSection": 577, "text": "Preclinical and clinical studies have shown that IVIG has anti-amyloid and immune modulatory properties relevant to treating neurodegenerative disorders. In early stage AD clinical trials, IVIG was found to reduce cognitive decline and increase brain glucose metabolism. Unfortunately, IVIG failed to meet primary outcome objectives in the North American Phase 3 clinical trial in mild to moderate AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760112", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1324, "text": "While the results of clinical trials to date do not provide support for the use of IVIG to treat AD at the doses tested, additional studies of IVIG's mechanisms are warranted and may guide the development of more effective therapies for AD in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760112", "endSection": "abstract" } ] }, { "body": "Which type of urinary incontinence is diagnosed with the Q tip test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3056562", "http://www.ncbi.nlm.nih.gov/pubmed/25315465", "http://www.ncbi.nlm.nih.gov/pubmed/23266205", "http://www.ncbi.nlm.nih.gov/pubmed/2724231", "http://www.ncbi.nlm.nih.gov/pubmed/3585870", "http://www.ncbi.nlm.nih.gov/pubmed/25134295", "http://www.ncbi.nlm.nih.gov/pubmed/23184140", "http://www.ncbi.nlm.nih.gov/pubmed/25966437", "http://www.ncbi.nlm.nih.gov/pubmed/22855114" ], "ideal_answer": [ "Stress urinary incontinence is diagnosed with the Q tip test. The test evaluates urethral mobility." ], "exact_answer": [ "stress urinary incontinence" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014549" ], "type": "factoid", "id": "5a67b2f7b750ff445500000f", "snippets": [ { "offsetInBeginSection": 194, "offsetInEndSection": 460, "text": "STUDY DESIGN: 141 women who agreed to undergo midurethral sling operations due to stress urinary incontinence with hypermobile urethra were enrolled in this non-randomized prospective observational study. Preoperatively, urethral mobility was measured by Q tip test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25966437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Valsalva leak point pressure-associated Q-tip angle and simple female stress urinary incontinence symptoms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315465", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 514, "text": "PURPOSE: To clarify the association between clinically defined simple stress urinary incontinence (SUI) symptoms and urodynamic SUI, we examined the relationship between Valsalva leak point pressure (VLPP) as measured by the Q-tip test and Stamey grade in simple female SUI.METHODS: Two hundred grade I or II female SUI patients with SUI symptom were examined by reviewing medical history; physical examination; urethral mobility as assessed by Q-tip test; stress test; and cystometry, including VLPP measurement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315465", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1463, "text": "CONCLUSIONS: In simple female SUI, VLPP is associated with the Q-tip angle and Stamey grade, which may help to reduce some of urodynamic items.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315465", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 493, "text": "Each woman at 12 and 24 months underwent postoperative evaluation by means of urodynamics, Q-tip test, CST, transperineal ultrasonography, and administration of \"King's Health Questionnaire\" (KHQ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25134295", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 741, "text": "METHODS: A total of 25 women affected by clinical stress urinary incontinence (SUI) were enrolled. After undergoing urodynamic assessment, pelvic organ prolapse quantification, urine culture, Q-tip test, and stress test, each subject underwent color Doppler ultrasonography to record clitoral blood flow and EMG of the urethral sphincter with a needle electrode inserted through the mucosa into the muscle tissue before surgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22855114", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 640, "text": "Preoperatively, patients underwent POP-Q staging, Q-tip test, challenge stress test and urodynamics, and completed the I-QoL, PISQ-12, and PGI-S questionnaires.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23266205", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 613, "text": "MATERIALS AND METHODS: One hundred patients suffering from clinical and/or urodynamic stress urinary incontinence (SUI) were randomized into biological material TOT (PELVILACE\u00ae TO) or synthetic material TOT (ALIGN\u00aeTO Urethral Support System) groups. Preoperative and at 1 year postoperative urogynecological symptom assessment, 1-h pad test, 4-day bladder diary, stress test, Q-tip test, and urodynamics were performed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23184140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Role of the Q-tip test in evaluating stress urinary incontinence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3585870", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Fifteen women with a clinical and urodynamic diagnosis of stress urinary incontinence had a negative Q-tip test (greater than or equal to 30 degrees Q-tip angle change on straining).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2724231", "endSection": "abstract" }, { "offsetInBeginSection": 1366, "offsetInEndSection": 1518, "text": "Simple clinical tests for support of the urethrovesical junction, such as the Q tip test, are non-specific in patients with stress urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3056562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "PURPOSE To clarify the association between clinically defined simple stress urinary incontinence (SUI) symptoms and urodynamic SUI, we examined the relationship between Valsalva leak point pressure (VLPP) as measured by the Q-tip test and Stamey grade in simple female SUI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25315465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Role of the Q-tip test in evaluating stress urinary incontinence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3585870", "endSection": "title" } ] }, { "body": "Does a tonsillectomy affect the patient's voice?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9181534", "http://www.ncbi.nlm.nih.gov/pubmed/9082794", "http://www.ncbi.nlm.nih.gov/pubmed/27554507", "http://www.ncbi.nlm.nih.gov/pubmed/21074280", "http://www.ncbi.nlm.nih.gov/pubmed/10864107", "http://www.ncbi.nlm.nih.gov/pubmed/18468843", "http://www.ncbi.nlm.nih.gov/pubmed/135896", "http://www.ncbi.nlm.nih.gov/pubmed/22803405", "http://www.ncbi.nlm.nih.gov/pubmed/26846544", "http://www.ncbi.nlm.nih.gov/pubmed/22242470", "http://www.ncbi.nlm.nih.gov/pubmed/17456652", "http://www.ncbi.nlm.nih.gov/pubmed/18025311", "http://www.ncbi.nlm.nih.gov/pubmed/12161728" ], "ideal_answer": [ "Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy. Group B had a better awareness of tooth damage . There were no differences in secondary outcomes across treatment groups. The incidence rates of voice change, velopharyngeal insufficiency, bleeding, constipation, dehydration, and pain were measured. ", "yes", " Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy. There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change.", "Voice change, reported by approximately 70% of all patients, was the most common complaint, but it resolved in all instances." ], "exact_answer": "yes", "type": "yesno", "id": "59bf823b542ba3824b000001", "snippets": [ { "offsetInBeginSection": 1021, "offsetInEndSection": 1307, "text": " Group B had a better awareness of tooth damage (78% vs 30% of patients, P \u2264 .001), voice change (61 vs 19%, P = .005), and burns to lips and mouth (44% vs 8%, P = .005). Finally, 35% more patients from group B rated their understanding of tonsillectomy as good or very good (P = .017).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27554507", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 570, "text": " Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22242470", "endSection": "abstract" }, { "offsetInBeginSection": 1572, "offsetInEndSection": 1680, "text": "The percentage of patients who had temporary voice change was 62.7%, and 15.4% had a follow-up clinic visit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17456652", "endSection": "title" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1023, "text": "There were no differences in secondary outcomes (analgesic requirements, time to first liquid, and change in voice) across treatment groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17456652", "endSection": "abstract" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1567, "text": "Voice change, reported by approximately 70% of all patients, was the most common complaint, but it resolved in all instances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10864107", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1177, "text": "The incidence rates of voice change, velopharyngeal insufficiency, bleeding, constipation, dehydration, and pain were measured. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10864107", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1198, "text": "Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26846544", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1641, "text": "The surgical technique, whether it is cold knife or thermal welding system, does not appear to affect voice and speech in tonsillectomy patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21074280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "OBJECTIVE: To evaluate changes in acoustic features of voice after tonsillectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22803405", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 797, "text": "Surgical indications for tonsillectomy in the young voice patient are discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9181534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "OBJECTIVE: Our goal was to assess patient perception and acoustic characteristics of voice before and after upper airway surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12161728", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 270, "text": "In this report, we examined the change in pharyngeal size and acoustic feature of voice after tonsillectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9082794", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1270, "text": "CONCLUSION Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26846544", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 573, "text": "Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22242470", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1199, "text": "Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26846544", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1642, "text": "The surgical technique, whether it is cold knife or thermal welding system, does not appear to affect voice and speech in tonsillectomy patients..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21074280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17456652", "endSection": "title" } ] }, { "body": "List the four most important interferonopathies", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27863149", "http://www.ncbi.nlm.nih.gov/pubmed/28844088", "http://www.ncbi.nlm.nih.gov/pubmed/27678529", "http://www.ncbi.nlm.nih.gov/pubmed/27821552", "http://www.ncbi.nlm.nih.gov/pubmed/28519900", "http://www.ncbi.nlm.nih.gov/pubmed/28585220", "http://www.ncbi.nlm.nih.gov/pubmed/28578473", "http://www.ncbi.nlm.nih.gov/pubmed/28089741" ], "ideal_answer": [ "Aicardi-Gouti\u00e8res syndrome\nchilblain lupus\nubiquitin specific peptidase 18 (USP18)-deficiency\nSingleton-Merten syndrome", "Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed \"interferonopathies\" including Aicardi-Goutieres syndrome, ubiquitin specific peptidase 18 (USP18)-deficiency, haploinsufficiency in A20, otulipenia, familial chiblain lupus." ], "exact_answer": [ [ "Aicardi-Gouti\u00e8res syndrome" ], [ "chilblain lupus" ], [ "ubiquitin specific peptidase 18 (USP18)-deficiency" ], [ "Singleton-Merten syndrome" ] ], "type": "list", "id": "5a882b5761bb38fb24000013", "snippets": [ { "offsetInBeginSection": 167, "offsetInEndSection": 326, "text": "As defined, the type I interferonopathies represent discrete examples of a disturbance of the homeostatic control of this system caused by Mendelian mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27821552", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 166, "text": "Familial chilblain lupus belongs to the group of type I interferonopathies and is characterized by typical skin manifestations and acral ischaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28844088", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 165, "text": "interferonopathies such as Aicardi-Gouti\u00e8res syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27863149", "endSection": "abstract" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1178, "text": "Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed \"interferonopathies\" including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)-deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28519900", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 789, "text": " interferonopathies (Singleton-Merten syndrome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28585220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Aicardi-Gouti\u00e8res syndrome (AGS) is an inflammatory disorder belonging to the recently characterized group of type I interferonopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28089741", "endSection": "abstract" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1179, "text": "Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed \"interferonopathies\" including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)-deficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28519900", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 928, "text": "Then, major players driving autoinflammation, such as type-1 interferonopathies (including the recently described haploinsuffiency in A20 and otulipenia), TNF-associated periodic syndromes, defects in ubiquitination, and SAID with overlapping features of autoimmunity or immunodeficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28578473", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 167, "text": "Familial chilblain lupus belongs to the group of type I interferonopathies and is characterized by typical skin manifestations and acral ischaemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28844088", "endSection": "abstract" } ] }, { "body": "List the partners of budding yeast Cdc48 that are important for disassembly of ubiquitylated CMG helicase at the end of chromosome replication", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28355556" ], "ideal_answer": [ "The ubiquitin-binding Ufd1-Npl4 complex recruits Cdc48 to ubiquitylated CMG helicase at the end of chromosome replication." ], "exact_answer": [ [ "Ufd1" ], [ "Npl4" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D029701", "http://www.biosemantics.org/jochem#4263266", "https://meshb.nlm.nih.gov/record/ui?ui=D004265", "https://meshb.nlm.nih.gov/record/ui?ui=D004261" ], "type": "list", "id": "5a6d1143b750ff445500002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Ufd1-Npl4 Recruit Cdc48 for Disassembly of Ubiquitylated CMG Helicase at the End of Chromosome Replication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28355556", "endSection": "title" }, { "offsetInBeginSection": 426, "offsetInEndSection": 522, "text": "We demonstrate that the ubiquitin-binding Ufd1-Npl4 complex recruits Cdc48 to ubiquitylated CMG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28355556", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 988, "text": "Mutation of K29 abrogates in\u00a0vitro recruitment of Ufd1-Npl4-Cdc48 to the CMG helicase, supporting a model whereby Ufd1-Npl4 recruits Cdc48 to ubiquitylated CMG at the end of chromosome replication, thereby driving the disassembly reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28355556", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 992, "text": "Mutation of K29 abrogates in\u00a0vitro recruitment of Ufd1-Npl4-Cdc48 to the CMG helicase, supporting a model whereby Ufd1-Npl4 recruits Cdc48 to ubiquitylated CMG at the end of chromosome replication, thereby driving the disassembly reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28355556", "endSection": "abstract" } ] }, { "body": "How are topologically associating domains (TAD) associated with replication timing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "http://www.ncbi.nlm.nih.gov/pubmed/28348222", "http://www.ncbi.nlm.nih.gov/pubmed/28977529", "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "http://www.ncbi.nlm.nih.gov/pubmed/27312344" ], "ideal_answer": [ "Topologically associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program. Topologically associating domains are stable units of replication-timing regulation.", "Topologically associating domains are stable units of replication-timing regulation. Both TADs and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program. Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs).", "Topologically associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program." ], "type": "summary", "id": "58ee217feda5a57672000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Topologically associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "endSection": "title" }, { "offsetInBeginSection": 539, "offsetInEndSection": 788, "text": "Determinants of the replication-timing program are re-established during early G1 phase of each cell cycle and lost in G2 phase, but it is not known when TAD structure and inter-TAD contacts are re-established after their elimination during mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "endSection": "abstract" }, { "offsetInBeginSection": 889, "offsetInEndSection": 1061, "text": "We find that both establishment of TADs and their compartmentalization occur during early G1, within the same time frame as establishment of the replication-timing program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1641, "text": " Overall, this study uncovers a strong connection between chromatin re-organization during G1, establishment of replication timing, and its developmental control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Topologically associating domains are stable units of replication-timing regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "title" }, { "offsetInBeginSection": 444, "offsetInEndSection": 720, "text": "Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "abstract" }, { "offsetInBeginSection": 1399, "offsetInEndSection": 1700, "text": "We demonstrate that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replication domain boundaries, largely accounting for the previously reported lack of alignment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 538, "text": "Hi-C also segregates inter-TAD contacts into defined 3D spatial compartments that align precisely to genome-wide replication timing profiles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 991, "text": "With a novel domain-based alignment proposed by us, we defined several types of hierarchical TAD changes which were not systematically studied previously, and subsequently used them to reveal that TADs and sub-TADs differed statistically in correlating chromosomal compartment, replication timing and gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28977529", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 1001, "text": "To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28348222", "endSection": "abstract" }, { "offsetInBeginSection": 1399, "offsetInEndSection": 1699, "text": "We demonstrate that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replication domain boundaries, largely accounting for the previously reported lack of alignment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "abstract" }, { "offsetInBeginSection": 1700, "offsetInEndSection": 2063, "text": "Moreover, cell-type-specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the reduced correlation of replication timing to LADs and heterochromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The genome of metazoan cells is organized into topologically associating domains (TADs) that have similar histone modifications, transcription level, and DNA replication timing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28348222", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 396, "text": "Genome-wide chromatin conformation capture (Hi-C) has revealed sub-megabase topologically associating domains (TADs), which are the structural counterparts of replication domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Topologically associating domains are stable units of replication-timing regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409831", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Topologically associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25995270", "endSection": "title" } ] }, { "body": "How are cryptic unstable transcripts (CUTs) defined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18660821", "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "http://www.ncbi.nlm.nih.gov/pubmed/19096707", "http://www.ncbi.nlm.nih.gov/pubmed/27345571", "http://www.ncbi.nlm.nih.gov/pubmed/25680078", "http://www.ncbi.nlm.nih.gov/pubmed/18022358", "http://www.ncbi.nlm.nih.gov/pubmed/27113450", "http://www.ncbi.nlm.nih.gov/pubmed/21826286", "http://www.ncbi.nlm.nih.gov/pubmed/28468764", "http://www.ncbi.nlm.nih.gov/pubmed/22567365", "http://www.ncbi.nlm.nih.gov/pubmed/27492286", "http://www.ncbi.nlm.nih.gov/pubmed/19169243", "http://www.ncbi.nlm.nih.gov/pubmed/19169244" ], "ideal_answer": [ "This resource includes deletions of small nuclear RNAs (snRNAs), transfer RNAs (tRNAs), small nucleolar RNAs (snoRNAs), and other annotated ncRNAs as well as the more recently identified stable unannotated transcripts (SUTs) and cryptic unstable transcripts (CUTs) whose functions are largely unknown There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs)", "There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. The transcription of CUTs predominantly arises within nucleosome-free regions, most of which correspond to promoter regions of bona fide genes. Most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by-products of divergent transcription occurring at many and possibly most promoters. Regulatory mechanisms involving expression of a CUT are diverse and include attenuation, transcriptional interference, and alternative transcription start site choice", "Here, by examining the overlap of stable (SUTs, stable unannotated transcripts) and unstable (CUTs, cryptic unstable transcripts) transcripts with protein-coding genes, we show that the predicted Nrd1 and Nab3-binding site sequences occur at differing frequencies. It is well established that eukaryotic genomes are pervasively transcribed producing cryptic unstable transcripts (CUTs). These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs) There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts.", "Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae.", "This resource includes deletions of small nuclear RNAs (snRNAs), transfer RNAs (tRNAs), small nucleolar RNAs (snoRNAs), and other annotated ncRNAs as well as the more recently identified stable unannotated transcripts (SUTs) and cryptic unstable transcripts (CUTs) whose functions are largely unknown There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. In this paper, we show that Nrd1 and Nab3 are required for transcription termination of CUTs These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts." ], "type": "summary", "id": "5a859184faa1ab7d2e000031", "snippets": [ { "offsetInBeginSection": 275, "offsetInEndSection": 575, "text": "This resource includes deletions of small nuclear RNAs (snRNAs), transfer RNAs (tRNAs), small nucleolar RNAs (snoRNAs), and other annotated ncRNAs as well as the more recently identified stable unannotated transcripts (SUTs) and cryptic unstable transcripts (CUTs) whose functions are largely unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28468764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18022358", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 204, "text": "These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 467, "text": "In this paper, we show that Nrd1 and Nab3 are required for transcription termination of CUTs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1057, "text": "These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16973436", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1278, "text": " It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19096707", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 402, "text": "These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169243", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 630, "text": "One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169243", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 792, "text": "Single-gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs or their generation itself", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169243", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1328, "text": "We show that both SUTs and CUTs display distinct patterns of distribution at specific locations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169243", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 312, "text": "Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 603, "text": "Although CUT degradation mechanisms have been analysed in detail, the genome-wide distribution at the nucleotide resolution and the prevalence of CUTs are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 786, "text": "Here we report the first high-resolution genomic map of CUTs in yeast, revealing a class of potentially functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1126, "text": " The resulting detailed genomic map of CUTs revealed that they derive from extremely widespread and very well defined transcription units and do not result from unspecific transcriptional noise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1280, "text": "the transcription of CUTs predominantly arises within nucleosome-free regions, most of which correspond to promoter regions of bona fide genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1358, "text": "Some of the CUTs start upstream from messenger RNAs and overlap their 5' end.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 1617, "offsetInEndSection": 1836, "text": "most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by-products of divergent transcription occurring at many and possibly most promoters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19169244", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 541, "text": "Most of these ncRNAs (ncRNAs) are subject to termination by the Nrd1-dependent pathway and rapid degradation by the nuclear exosome and have been dubbed cryptic unstable transcripts (CUTs). CUTs are often considered as by-products of transcriptional noise, but in an increasing number of cases they play a central role in the control of gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22567365", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 709, "text": "Regulatory mechanisms involving expression of a CUT are diverse and include attenuation, transcriptional interference, and alternative transcription start site choice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22567365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "It is well established that eukaryotic genomes are pervasively transcribed producing cryptic unstable transcripts (CUTs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27345571", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 449, "text": "We show that loss of abp1 results in the accumulation of CUTs, which are targeted for degradation by the exosome pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27345571", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 775, "text": "Here, by examining the overlap of stable (SUTs, stable unannotated transcripts) and unstable (CUTs, cryptic unstable transcripts) transcripts with protein-coding genes, we show that the predicted Nrd1 and Nab3-binding site sequences occur at differing frequencies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27492286", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 282, "text": "Cryptic unstable transcripts (CUTs) are a largely unexplored class of nuclear exosome degraded, non-coding RNAs in budding yeast. It is highly debated whether CUT transcription has a functional role in the cell or whether CUTs represent noise in the yeast transcriptome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27113450", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 1090, "text": " By identifying configurations of gene-CUT pairs, where CUT expression originates from the gene 5' or 3' nucleosome free region, we observed distinct gene expression trends specific to these configurations which were most prevalent in the presence of conserved CUT expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27113450", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1553, "text": "Furthermore we provide the first assessment of conserved CUT expression in yeast and globally demonstrate possible modes of CUT-based regulation of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27113450", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 378, "text": "Most of these ncRNAs (ncRNAs) are subject to termination by the Nrd1-dependent pathway and rapid degradation by the nuclear exosome and have been dubbed cryptic unstable transcripts (CUTs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22567365", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 350, "text": "Some are designated Cryptic Unstable Transcripts (CUTs) because they are terminated by the Nrd1-Nab3-Sen1 pathway and then rapidly degraded by the nuclear exosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21826286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Cryptic unstable transcripts (CUTs) are short, 300-600-nucleotide (nt) RNA polymerase II transcripts that are rapidly degraded by the nuclear RNA exosome in yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18660821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND Cryptic unstable transcripts (CUTs) are a largely unexplored class of nuclear exosome degraded, non-coding RNAs in budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27113450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Cryptic unstable transcripts (CUTs) are a largely unexplored class of nuclear exosome degraded, non-coding RNAs in budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27113450", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 516, "text": "Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680078", "endSection": "abstract" } ] }, { "body": "How many Groucho-related genes (GRG) are contained in the mouse genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8989517", "http://www.ncbi.nlm.nih.gov/pubmed/8955148", "http://www.ncbi.nlm.nih.gov/pubmed/7916324", "http://www.ncbi.nlm.nih.gov/pubmed/8867791", "http://www.ncbi.nlm.nih.gov/pubmed/8573724", "http://www.ncbi.nlm.nih.gov/pubmed/8892234", "http://www.ncbi.nlm.nih.gov/pubmed/20925119" ], "ideal_answer": [ "It spans approximately 7 kb on chromosome 10 and consists of seven exons. The groucho-related genes (Grg) of the mouse comprise at least four family members.", "The groucho-related genes of the mouse comprise at least four family members. The Grg gene encodes a 197 amino acid protein homologous to the amino-terminal domain of the product of the groucho gene of the Drosophila Enhancer of split complex. The murine grg products are believed to interact with transcription factors and repress transcription, thereby regulating cell proliferation and differentiation. ", "The groucho-related genes (Grg) of the mouse comprise at least four family members.", "We have isolated cDNAs representing multiple members of murine groucho homologues, designated Grg for groucho-related genes. The groucho-related genes (Grg) of the mouse comprise at least four family members." ], "exact_answer": [ "four", "4" ], "type": "factoid", "id": "593ff22b70f9fc6f0f000023", "snippets": [ { "offsetInBeginSection": 165, "offsetInEndSection": 304, "text": " We describe here the genomic organization of the mouse Grg gene. It spans approximately 7 kb on chromosome 10 and consists of seven exons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7916324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The Grg gene encodes a 197 amino acid protein homologous to the amino-terminal domain of the product of the groucho gene of the Drosophila Enhancer of split complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8573724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The mouse Grg gene encodes a 197 amino acid nuclear protein homologous to the amino-terminal domain of the product of the groucho (gro) gene of the Drosophila Enhancer of split complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8867791", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "The groucho-related genes (Grg) of the mouse comprise at least four family members.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8892234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The murine grg (Groucho-related gene) products are believed to interact with transcription factors and repress transcription, thereby regulating cell proliferation and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8955148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "We have isolated cDNAs representing multiple members of murine groucho homologues, designated Grg for groucho-related genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8989517", "endSection": "abstract" } ] }, { "body": "What is mechanism of action of galunisertib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26309397", "http://www.ncbi.nlm.nih.gov/pubmed/27756784", "http://www.ncbi.nlm.nih.gov/pubmed/26057634", "http://www.ncbi.nlm.nih.gov/pubmed/28230858", "http://www.ncbi.nlm.nih.gov/pubmed/27166186", "http://www.ncbi.nlm.nih.gov/pubmed/27872101", "http://www.ncbi.nlm.nih.gov/pubmed/28691737", "http://www.ncbi.nlm.nih.gov/pubmed/28436712", "http://www.ncbi.nlm.nih.gov/pubmed/27509307", "http://www.ncbi.nlm.nih.gov/pubmed/28481241", "http://www.ncbi.nlm.nih.gov/pubmed/26902851", "http://www.ncbi.nlm.nih.gov/pubmed/29145888" ], "ideal_answer": [ "Galunisertib is a transforming growth factor-\u03b2 receptor type I kinase inhibitor (TGF-\u03b2RI). It was tested for treatment of solid cancers, including glioblastoma and neuroblastoma, and liver fibrosis." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D045504" ], "type": "summary", "id": "5a7604de83b0d9ea66000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "TGF\u03b2R1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756784", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 339, "text": "Galunisertib, an inhibitor of TGF\u03b2R1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756784", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 356, "text": "Consequently, blockade of TGF\u03b2 signaling with galunisertib in combination with the anti-GD2 mAb dinutuximab plus adoptively transferred NK cells is a promising tool for the treatment of neuroblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27872101", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 307, "text": "The small molecule kinase inhibitor galunisertib, targeting the TGF-\u03b2 receptor I (TGF-\u03b2RI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28230858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Galunisertib, a Transforming growth factor-\u03b2RI (TGF-\u03b2RI) kinase inhibitor, blocks TGF-\u03b2-mediated tumor growth in glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28481241", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 259, "text": "Galunisertib, a TGF-\u03b2 receptor type I kinase inhibitor, is a potential candidate for the treatment of liver fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28691737", "endSection": "abstract" }, { "offsetInBeginSection": 1642, "offsetInEndSection": 1805, "text": "A xenograft model provided additional confirmation on combination of TGF-\u03b2 inhibitor (Galunisertib) and autophagy inhibitor (CQ) to better \"turn off\" tumor growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29145888", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1342, "text": "urther targeting TGF-\u03b2/Smad3 signaling using galunisertib, an inhibitor of the TGF-\u03b2 type I receptor kinase, can attenuate the secretion of miR-21 from glioma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27166186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Disposition and metabolism of [C]-galunisertib, a TGF-\u03b2RI kinase/ALK5 inhibitor, following oral administration in healthy subjects and mechanistic prediction of the effect of itraconazole on galunisertib pharmacokinetics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28436712", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The combination of galunisertib, a transforming growth factor (TGF)-\u03b2 receptor (R)1 kinase inhibitor, and lomustine was found to have antitumor activity in murine models of glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "1.\u2003The disposition and metabolism of galunisertib (LY2157299 monohydrate, a TGF-\u03b2RI Kinase/ALK5 Inhibitor) was characterized following a single oral dose of 150\u2009mg of [C]-galunisertib (100\u2009\u00b5Ci) to six healthy human subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28436712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26057634", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26309397", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-\u03b2 receptor I (TGF-\u03b2RI), is the only known TGF-\u03b2 pathway inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27509307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-\u03b2 receptor (T\u03b2R)-I activation currently under clinical investigation in hepatocellular carcinoma (HCC) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26057634", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 696, "text": "Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-\u03b2 receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26309397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Galunisertib, a Transforming growth factor-\u03b2RI (TGF-\u03b2RI) kinase inhibitor, blocks TGF-\u03b2-mediated tumor growth in glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28481241", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 310, "text": "The small molecule kinase inhibitor galunisertib, targeting the TGF-\u03b2 receptor I (TGF-\u03b2RI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28230858", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 258, "text": "Galunisertib, a TGF-\u03b2 receptor type I kinase inhibitor, is a potential candidate for the treatment of liver fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28691737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND The combination of galunisertib, a transforming growth factor (TGF)-\u03b2 receptor (R)1 kinase inhibitor, and lomustine was found to have antitumor activity in murine models of glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902851", "endSection": "abstract" } ] }, { "body": "What is a coligo?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25764216", "http://www.ncbi.nlm.nih.gov/pubmed/27593562" ], "ideal_answer": [ "Coligos are circularized oligodeoxynucleotides" ], "exact_answer": [ "circularized oligodeoxynucleotides" ], "type": "factoid", "id": "5a87ea1861bb38fb2400000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Circularized oligonucleotides, or coligos,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27593562", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 304, "text": "circularized oligodeoxynucleotides (coligos)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764216", "endSection": "abstract" } ] }, { "body": "What is the relationship of fyn kinase and tau?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28420443", "http://www.ncbi.nlm.nih.gov/pubmed/28709498" ], "ideal_answer": [ "The Fyn kinase interacts with tau. The activated Fyn kinase hyperphosphorylates the tau protein." ], "type": "summary", "id": "5a774240faa1ab7d2e000003", "snippets": [ { "offsetInBeginSection": 1120, "offsetInEndSection": 1330, "text": "Fyn is an attractive target for AD therapeutics, not only based on its activation by A\u03b2 via cellular prion protein but also due to its known interaction with tau, uniquely linking the two key pathologies in AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28709498", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 385, "text": "This PrPC-A\u03b2o complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P-Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28420443", "endSection": "abstract" } ] }, { "body": "Which are the main manifestations of Ohdo syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10706355", "http://www.ncbi.nlm.nih.gov/pubmed/27500536", "http://www.ncbi.nlm.nih.gov/pubmed/27312080", "http://www.ncbi.nlm.nih.gov/pubmed/15127758" ], "ideal_answer": [ "Severe ID, absent or deficient language, skeletal manifestations including bilateral patella dislocations." ], "exact_answer": [ [ "intellectual disability", "ID" ], [ "deficient language" ], [ "bilateral patella dislocations" ], [ "skeletal manifestations" ] ], "type": "list", "id": "58f8a08370f9fc6f0f00001b", "snippets": [ { "offsetInBeginSection": 802, "offsetInEndSection": 1072, "text": " This finding together with the phenotypic analogies shared with the carriers of c.5898dupC mutation suggests the existence of a fourth MED12-related disorder, characterized by severe ID, absent or deficient language and, milder, clinical manifestation in heterozygotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27312080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Skeletal manifestations in Ohdo syndrome: a case with bilateral patella dislocations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15127758", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "We report a new case of Ohdo syndrome with bilateral patella dislocations where surgical intervention has been indicated. A review of the skeletal manifestations reported in the literature on Ohdo syndrome reveals that joint laxity and skeletal deformities are important aspects of the phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15127758", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 482, "text": "We confirm the existence of this condition that, although similar to Ohdo syndrome, seems to be an independent clinical entity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10706355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "We report a new case of Ohdo syndrome with bilateral patella dislocations where surgical intervention has been indicated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15127758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Skeletal manifestations in Ohdo syndrome: a case with bilateral patella dislocations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15127758", "endSection": "title" }, { "offsetInBeginSection": 803, "offsetInEndSection": 1072, "text": "This finding together with the phenotypic analogies shared with the carriers of c.5898dupC mutation suggests the existence of a fourth MED12-related disorder, characterized by severe ID, absent or deficient language and, milder, clinical manifestation in heterozygotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27312080", "endSection": "abstract" } ] }, { "body": "Which algorithm is used by the UCSC Genome Browser?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22908213", "http://www.ncbi.nlm.nih.gov/pubmed/22080555", "http://www.ncbi.nlm.nih.gov/pubmed/24984850", "http://www.ncbi.nlm.nih.gov/pubmed/23255150", "http://www.ncbi.nlm.nih.gov/pubmed/18428780", "http://www.ncbi.nlm.nih.gov/pubmed/27574198", "http://www.ncbi.nlm.nih.gov/pubmed/17993665", "http://www.ncbi.nlm.nih.gov/pubmed/12519945", "http://www.ncbi.nlm.nih.gov/pubmed/21975940", "http://www.ncbi.nlm.nih.gov/pubmed/24227676", "http://www.ncbi.nlm.nih.gov/pubmed/19957273" ], "ideal_answer": [ "The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files.", "The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Binary Alignment/Map , where the differences between the data set and the reference assembly may be displayed graphically. The Saved Session feature allows users to store and share customized views, enhancing the utility of the system for organizing multiple trains of thought. The University of California Santa Cruz is a popular Web-based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation \"tracks\". The UCSC Genome Browser organizes data and annotations around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. ", "The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels.", "The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser." ], "exact_answer": [ "Genome hashing" ], "type": "factoid", "id": "590af75d70f9fc6f0f00001c", "snippets": [ { "offsetInBeginSection": 578, "offsetInEndSection": 792, "text": "The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27574198", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 629, "text": "The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12519945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The University of California Santa Cruz (UCSC) Genome Browser (genome.ucsc.edu) is a popular Web-based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation \"tracks\". ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428780", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 800, "text": " The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The University of California Santa Cruz (UCSC) Genome Browser is a popular Web-based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation \"tracks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21975940", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1779, "text": "The Saved Session feature allows users to store and share customized views, enhancing the utility of the system for organizing multiple trains of thought. Binary Alignment/Map (BAM), Variant Call Format and the Personal Genome Single Nucleotide Polymorphisms (SNPs) data formats are useful for visualizing a large sequencing experiment (whole-genome or whole-exome), where the differences between the data set and the reference assembly may be displayed graphically. Support for high-throughput sequencing extends to compact, indexed data formats, such as BAM, bigBed and bigWig, allowing rapid visualization of large datasets from RNA-seq and ChIP-seq experiments via local hosting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908213", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 800, "text": "The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428780", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 812, "text": "The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23255150", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 812, "text": "The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19957273", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 836, "text": "The comparative genomics annotations in the browser include pairwise alignments, which aid in the identification of orthologous regions between species, and conservation tracks that show measures of evolutionary conservation among sets of multiply aligned species, highlighting regions of the genome that may be functionally important.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17993665", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 500, "text": "Genome Bioinformatics group has developed several tools and methodologies in its study of comparative genomics, many of which have been incorporated into the UCSC Genome Browser (http://genome.ucsc.edu), an easy-to-use online tool for browsing genomic data and aligned annotation \"tracks\" in a single window.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17993665", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1039, "text": "This protocol describes how to use the UCSC Genome Browser to visualize selected tracks at specified genomic regions, download the data and annotations for further analysis, and retrieve multiple sequence alignments and their conservation scores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27574198", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1088, "text": "This unit describes how to use the Genome Browser and Table Browser for genome analysis, download the underlying database tables, and create and display custom annotation tracks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The University of California Santa Cruz (UCSC) Genome Browser (genome.ucsc.edu) is a popular Web-based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation \"tracks\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18428780", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 500, "text": "The University of California Santa Cruz (UCSC) Genome Bioinformatics group has developed several tools and methodologies in its study of comparative genomics, many of which have been incorporated into the UCSC Genome Browser (http://genome.ucsc.edu), an easy-to-use online tool for browsing genomic data and aligned annotation \"tracks\" in a single window.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17993665", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1003, "text": "A related tool, the UCSC Table Browser, provides a simple interface for querying, analyzing, and downloading the data underlying the Genome Browser annotation tracks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17993665", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1111, "text": "Some of the recently developed or enhanced tracks visualize data from published high-throughput RNA-sequencing studies, the NCBI Conserved Domain Database, sequences from pre-genome sequencing studies, predicted gene boundaries from three different protein gene prediction algorithms, tRNAscan-SE gene predictions with RNA secondary structures and CRISPR locus predictions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080555", "endSection": "abstract" } ] }, { "body": "Which aminoacid position in the human CREB protein is phosphorylated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27480489", "http://www.ncbi.nlm.nih.gov/pubmed/28185187" ], "ideal_answer": [ "pCREB is phosphorylated at its Serine 133." ], "exact_answer": [ "Ser133" ], "type": "factoid", "id": "5a8941c5bc7bade53a000002", "snippets": [ { "offsetInBeginSection": 501, "offsetInEndSection": 533, "text": " pCREB(Ser133) as a model system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28185187", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 364, "text": "CREB and its activated form pCREB-Ser(133) (pCREB) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27480489", "endSection": "abstract" } ] }, { "body": "Which gene is the paralog of yeast UPC2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21980509", "http://www.ncbi.nlm.nih.gov/pubmed/28986257", "http://www.ncbi.nlm.nih.gov/pubmed/24453983", "http://www.ncbi.nlm.nih.gov/pubmed/10073572", "http://www.ncbi.nlm.nih.gov/pubmed/18487346", "http://www.ncbi.nlm.nih.gov/pubmed/1885560", "http://www.ncbi.nlm.nih.gov/pubmed/11208779", "http://www.ncbi.nlm.nih.gov/pubmed/24163365", "http://www.ncbi.nlm.nih.gov/pubmed/23385756", "http://www.ncbi.nlm.nih.gov/pubmed/26448198", "http://www.ncbi.nlm.nih.gov/pubmed/28379181" ], "ideal_answer": [ "the related transcription factors Ecm22 and Upc2 play a crucial role in Saccharomyces cerevisiae filamentation.", "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation. The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways. ", "zinc cluster proteins Upc2 and Ecm22 promote filamentation", "The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways.Here, we examine the role of the related transcription factors ecm22 and upc2 in saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways.Here, we examine the role of the related transcription factors ecm22 and upc2 in saccharomyces cerevisiae filamentation.", "The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways. Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation. ", "The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways. Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation.", "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation. The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways.", "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation.The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways.", "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation." ], "exact_answer": [ "Ecm22" ], "type": "factoid", "id": "590c74d170f9fc6f0f00001e", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 305, "text": "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26448198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26448198", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Upc2, a zinc-cluster transcription factor, is a regulator of ergosterol biosynthesis in yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385756", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 275, "text": "The zinc cluster proteins Ecm22, Upc2, Sut1 and Sut2 have initially been identified as regulators of sterol import in the budding yeast Saccharomyces cerevisiae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28379181", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 386, "text": "Yeast studies defined a 7-bp consensus sterol-response element (SRE) common to genes involved in sterol biosynthesis and two transcription factors, Upc2 and Ecm22, which direct transcription of sterol biosynthetic genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163365", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 555, "text": "Ecm22 and Upc2 positively control the expression of FHN1, NPR1, PRR2 and sterol biosynthesis genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26448198", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1127, "text": "RNA-seq analysis shows that hypoxic regulation of sterol synthesis genes in Y. lipolytica is predominantly mediated by Upc2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24453983", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 404, "text": "However, in yeasts such as Saccharomyces cerevisiae and Candida albicans sterol synthesis is instead regulated by Upc2, an unrelated transcription factor with a Gal4-type zinc finger.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24453983", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1220, "text": "Recombinant endogenous promoter studies show that the UPC2 anaerobic AR1b elements act in trans to regulate ergosterol gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163365", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1293, "text": "One such factor could be the mammalian equivalent of the gene product of UPC2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1885560", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1162, "text": "Simultaneous deletion of ECM22 and UPC2 as well as mutation of the three Ste12-binding sites in the PRM1 promoter completely abolishes basal and pheromone-induced PRM1 expression, indicating that Ste12 and Ecm22/Upc2 control PRM1 transcription through distinct pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28986257", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 365, "text": "Ecm22 and Upc2 positively regulate basal expression of PRM1 and PRM4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28986257", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1340, "text": "Our results indicate that Upc2 must occupy UPC2 AR1b elements in order for ERG gene expression induction to take place.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163365", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 284, "text": "A yeast mutant (upc2-1) with a defect in the aerobic exclusion of sterols was found to have increased sensitivity to LiCl and NaCl.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10073572", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 898, "text": "The AR1b elements are absolutely required for auto-induction of UPC2 gene expression and protein and require Upc2 and Ecm22 for function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24163365", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 265, "text": "Secretion of apoE was achieved only by the use of a mutant (upc2) strain of yeast with the phenotype of enhanced uptake and intracellular esterification of exogenous cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1885560", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1560, "text": "Gas chromatographic analysis of the nonsaponifiable fractions of the various strains showed that the major sterol for all YLR228c and UPC2 combinations was ergosterol, the consensus yeast sterol..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11208779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "In the pathogenic yeast Candida albicans, the zinc cluster transcription factor Upc2p has been shown to regulate the expression of ERG11 and other genes involved in ergosterol biosynthesis upon exposure to azole antifungals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18487346", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1509, "text": "By comparing the gene expression profiles of the fluconazole-resistant isolate and of strains carrying wild-type and mutated UPC2 alleles, we identified target genes that are controlled by Upc2p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18487346", "endSection": "abstract" } ] }, { "body": "Where is the enzyme PM20D1 localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27374330", "http://www.ncbi.nlm.nih.gov/pubmed/27378359" ], "ideal_answer": [ "PM20D1 is enriched in UCP1+ adipocytes" ], "exact_answer": [ "UCP1+ adipocytes" ], "type": "factoid", "id": "5a89800efcd1d6a10c00000c", "snippets": [ { "offsetInBeginSection": 215, "offsetInEndSection": 343, "text": "we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27374330", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 707, "text": " A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27378359", "endSection": "abstract" } ] }, { "body": "Which test is used to diagnose colour synesthesia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16919755", "http://www.ncbi.nlm.nih.gov/pubmed/22512712", "http://www.ncbi.nlm.nih.gov/pubmed/23458658", "http://www.ncbi.nlm.nih.gov/pubmed/25793307" ], "ideal_answer": [ "A standardized test battery for the study of synesthesia. We used synesthetic versions of the Stroop test with colored letters and numbers presented either in the right or the left visual field of thirty-four synesthetes. Assessment of the hemispheric lateralization of grapheme-color synesthesia with Stroop-type tests. ", "Stroop-type testsWe", "We used synesthetic versions of the Stroop test with colored letters and numbers presented either in the right or the left visual field of thirty-four synesthetes" ], "exact_answer": [ "Stroop Test" ], "type": "factoid", "id": "5a3e8683966455904c000007", "snippets": [ { "offsetInBeginSection": 920, "offsetInEndSection": 1234, "text": "To remedy this deficit we have devised the Synesthesia Battery. This unified collection of tests is freely accessible online (http://www.synesthete.org). It consists of a questionnaire and several online software programs, and test results are immediately available for use by synesthetes and invited researchers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16919755", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "A standardized test battery for the study of synesthesia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16919755", "endSection": "title" }, { "offsetInBeginSection": 277, "offsetInEndSection": 374, "text": "The application and results of consistency, psychophysical, and Stroop tests are presented later.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22512712", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 840, "text": "This study aims to find the most reliable way of diagnosing grapheme-colour synaesthesia based on maximising sensitivity (i.e., ability of a test to identify true synaesthetes) and specificity (i.e., ability of a test to identify true non-synaesthetes).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23458658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Assessment of the hemispheric lateralization of grapheme-color synesthesia with Stroop-type tests", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793307", "endSection": "title" }, { "offsetInBeginSection": 311, "offsetInEndSection": 474, "text": "We used synesthetic versions of the Stroop test with colored letters and numbers presented either in the right or the left visual field of thirty-four synesthetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25793307", "endSection": "abstract" } ] }, { "body": "How does increased GDF15 affect body weight?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28846097" ], "ideal_answer": [ "In humans, elevated GDF15 correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake." ], "exact_answer": [ "Reduces body weight" ], "type": "factoid", "id": "5a7d5ce0faa1ab7d2e00001b", "snippets": [ { "offsetInBeginSection": 166, "offsetInEndSection": 606, "text": "In humans, elevated GDF15 correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake. The mechanisms through which GDF15 reduces body weight remain poorly understood, because the cognate receptor for GDF15 is unknown. Here we show that recombinant GDF15 induces weight loss in mice fed a high-fat diet and in nonhuman primates with spontaneous obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846097", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1013, "text": "Gfral is expressed in neurons of the area postrema and nucleus of the solitary tract in mice and humans, and genetic deletion of the receptor abrogates the ability of GDF15 to decrease food intake and body weight in mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846097", "endSection": "abstract" } ] }, { "body": "Which are the best methods for the prediction of circular RNA (circRNA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27739534", "http://www.ncbi.nlm.nih.gov/pubmed/26657634", "http://www.ncbi.nlm.nih.gov/pubmed/26873924", "http://www.ncbi.nlm.nih.gov/pubmed/27167008", "http://www.ncbi.nlm.nih.gov/pubmed/29165116", "http://www.ncbi.nlm.nih.gov/pubmed/26556385", "http://www.ncbi.nlm.nih.gov/pubmed/27493192" ], "ideal_answer": [ "A circRNA prediction software for plants . Circular RNA profile in gliomas revealed by identification tool UROBORUS. Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. MiARma-Seq: a comprehensive tool for miRNA, mRNA and circRNA analysis. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. ", "Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data. A circRNA prediction software for plants (termed PcircRNA_finder) was developed that is more sensitive in detecting circRNAs than other frequently used programs (such as find_circ and CIRCexplorer)", "Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data. Circular RNA profile in gliomas revealed by identification tool UROBORUS. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance.", "PcircRNAfinder : a software for circRNA prediction in plants. A circRNA expression from RNA sequencing here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNAfinder, findcirc, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. Numerous algorithms that are used to detect genome-wide circRNA prediction software for plants was developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect circRNAs in total RNA-seq data. MiARma-Seq : a comprehensive tool for miRNA, mRNA and circRNA analysis. Circular RNA profile in gliomas revealed by identification tool UROBORUS. ", "The best methods for the prediction of circular RNA are: circRNA_finder, find_circ, CIRCexplorer, CIRI, MapSplice, UROBORUS, Circ TEST DCC and miARma-Seq. ", "Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data. Circular RNA profile in gliomas revealed by identification tool UROBORUS." ], "exact_answer": [ [ "circRNA_finder" ], [ "find_circ" ], [ "CIRCexplorer" ], [ "CIRI" ], [ "MapSplice" ], [ "UROBORUS" ], [ "Circ TEST DCC" ], [ "miARma-Seq" ] ], "type": "list", "id": "5a43b2d7966455904c00000c", "snippets": [ { "offsetInBeginSection": 136, "offsetInEndSection": 415, "text": "Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27739534", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 525, "text": "We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26556385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Circular RNA profile in gliomas revealed by identification tool UROBORUS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26873924", "endSection": "title" }, { "offsetInBeginSection": 351, "offsetInEndSection": 465, "text": "In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26873924", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 751, "text": " Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26657634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "miARma-Seq: a comprehensive tool for miRNA, mRNA and circRNA analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27167008", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "PcircRNA_finder: a software for circRNA prediction in plants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493192", "endSection": "title" }, { "offsetInBeginSection": 344, "offsetInEndSection": 541, "text": "A circRNA prediction software for plants (termed PcircRNA_finder) was developed that is more sensitive in detecting circRNAs than other frequently used programs (such as find_circ and CIRCexplorer)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493192", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 267, "text": "Recently, circular RNA (circRNA), a class of endogenous non-protein coding RNAs that contain a circular loop, was found to exhibit multiple biological effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29165116", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 750, "text": "RESULTS A circRNA prediction software for plants (termed PcircRNA_finder) was developed that is more sensitive in detecting circRNAs than other frequently used programs (such as find_circ and CIRCexplorer), Based on analysis of simulated and real rRNA-/RNAase R RNA-Seq data from Arabidopsis thaliana and rice PcircRNA_finder provides a more comprehensive sensitive, precise prediction method for plants circRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493192", "endSection": "abstract" } ] }, { "body": "What is inhibited by a drug rilotumumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27568322", "http://www.ncbi.nlm.nih.gov/pubmed/28472537", "http://www.ncbi.nlm.nih.gov/pubmed/28280216", "http://www.ncbi.nlm.nih.gov/pubmed/27966237", "http://www.ncbi.nlm.nih.gov/pubmed/28958504", "http://www.ncbi.nlm.nih.gov/pubmed/28209746", "http://www.ncbi.nlm.nih.gov/pubmed/25712685", "http://www.ncbi.nlm.nih.gov/pubmed/24186235", "http://www.ncbi.nlm.nih.gov/pubmed/23136195" ], "ideal_answer": [ "Rilotumumab is a fully human monoclonal antibody that selectively targets the hepatocyte growth factor (HGF). It is used for treatment of cancer." ], "exact_answer": [ "hepatocyte growth factor" ], "type": "factoid", "id": "5a7617b183b0d9ea66000022", "snippets": [ { "offsetInBeginSection": 1123, "offsetInEndSection": 1344, "text": "The hepatocyte growth factor receptor (MET) was targeted in untreated patients in a phase III trial with MoAb rilotumumab, with or without CT, but the study was stopped because of mortality excess in the rilotumumab arm. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "AIMS: Rilotumumab is a fully human monoclonal antibody investigated for the treatment of MET-positive gastric cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27966237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The hepatocyte growth factor (HGF) binding antibody rilotumumab (AMG102) was modified for use as a89Zr-based immuno-PET imaging agent to noninvasively determine the local levels of HGF protein in tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28280216", "endSection": "abstract" }, { "offsetInBeginSection": 2187, "offsetInEndSection": 2384, "text": "Furthermore, negative study data have been published for rilotumumab and ficlatuzumab, both of which block hepatocyte growth factor binding to the mesenchymal-epithelial transition (MET) receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28209746", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 396, "text": "In this phase 1/2 trial, rilotumumab (an anti-HGF antibody) combined with erlotinib was evaluated in patients with metastatic, previously treated non-small cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28472537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Rilotumumab is a fully human monoclonal antibody that selectively targets the ligand of the MET receptor, hepatocyte growth factor (HGF). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28958504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Rilotumumab is an investigational, fully human, monoclonal antibody immunoglobulin G2 against hepatocyte growth factor (HGF) that blocks the binding of HGF to its receptor MET and has shown trends toward improved survival in a phase 2 clinical trial in gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24186235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "PURPOSE Rilotumumab is an investigational, fully human monoclonal antibody to hepatocyte growth factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25712685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "PURPOSE To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients with castration-resistant prostate cancer (CRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23136195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND Rilotumumab is a fully human monoclonal antibody that selectively targets the ligand of the MET receptor, hepatocyte growth factor (HGF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28958504", "endSection": "abstract" } ] }, { "body": "Which RNA polymerase II subunit carries RNA cleavage activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12692127", "http://www.ncbi.nlm.nih.gov/pubmed/9869639", "http://www.ncbi.nlm.nih.gov/pubmed/21450810", "http://www.ncbi.nlm.nih.gov/pubmed/26929337", "http://www.ncbi.nlm.nih.gov/pubmed/8636112", "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "http://www.ncbi.nlm.nih.gov/pubmed/7678416", "http://www.ncbi.nlm.nih.gov/pubmed/8599945", "http://www.ncbi.nlm.nih.gov/pubmed/8876173", "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "http://www.ncbi.nlm.nih.gov/pubmed/21454497", "http://www.ncbi.nlm.nih.gov/pubmed/22396529" ], "ideal_answer": [ "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.", "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex. The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II.", "In contrast, Pol II is fully protected through association with the cleavage stimulatory factor TFIIS, which enables rapid recovery from any depth by RNA cleavage.", "In contrast, Pol II is fully protected through association with the cleavage stimulatory factor TFIIS, which enables rapid recovery from any depth by RNA cleavage. This mechanism is also used by transcription factor IIS, a factor that can bind Pol II and induce strong RNA cleavage. " ], "exact_answer": [ "TFIIS" ], "type": "factoid", "id": "5a4df811966455904c00000e", "snippets": [ { "offsetInBeginSection": 851, "offsetInEndSection": 1014, "text": "In contrast, Pol II is fully protected through association with the cleavage stimulatory factor TFIIS, which enables rapid recovery from any depth by RNA cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26929337", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 816, "text": "This mechanism is also used by transcription factor IIS, a factor that can bind Pol II and induce strong RNA cleavage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21454497", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1100, "text": " This mutant enzyme can respond to SII for transcriptional read-through and carry out SII-activated nascent RNA cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8636112", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 1101, "text": " In vitro, in the absence of TFIIS, the purified wt polymerase and the two mutant polymerases showed similar specific activity in polymerization, readthrough at intrinsic transcriptional arrest sites and nascent RNA cleavage. In contrast to the wt polymerase, both mutant polymerases were not stimulated by the addition of a 3-fold molar excess of TFIIS in assays of promoter-independent transcription, readthrough or cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8876173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "In vitro characterization of mutant yeast RNA polymerase II with reduced binding for elongation factor TFIIS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8876173", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 396, "text": "By site-directed mutagenesis, we have demonstrated that invariant residues Asp-261 and Glu-262 of the nucleic acid-binding TFIIS Zn ribbon are critical for stimulation of both elongation and RNA cleavage activities of RNA polymerase II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 454, "text": "Highly purified yeast RNA polymerase II is able to perform transcript hydrolysis in the absence of TFIIS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12692127", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 395, "text": "By site-directed mutagenesis, we have demonstrated that invariant residues Asp-261 and Glu-262 of the nucleic acid-binding TFIIS Zn ribbon are critical for stimulation of both elongation and RNA cleavage activities of RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The transcription elongation factor S-II, also designated TFIIS, stimulates the nascent transcript cleavage activity intrinsic to RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 884, "text": "The RNA polymerase II itself may contain a Zn ribbon, in as much as the polymerase's 15-kDa subunit contains a sequence that aligns well with the TFIIS Zn ribbon sequence, including a similarly placed pair of acidic residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8090778", "endSection": "abstract" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1164, "text": "Involvement of the vaccinia RNA polymerase subunit rpo30 in the transcript-shortening reaction is suggested based on sequence similarity of rpo30 to mammalian protein SII (TFIIS), an extrinsic transcription factor required for nascent RNA cleavage by RNA polymerase II (Reines, D. (1991) J. Biol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7678416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The RNA cleavage activity of RNA polymerase III is mediated by an essential TFIIS-like subunit and is important for transcription termination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9869639", "endSection": "title" }, { "offsetInBeginSection": 560, "offsetInEndSection": 869, "text": "In the resulting model of Pol I, the C-terminal ribbon (C-ribbon) domain of A12.2 reaches the active site via the polymerase pore, like the C-ribbon of the Pol II cleavage factor TFIIS, explaining why the intrinsic RNA cleavage activity of Pol I is strong, in contrast to the weak cleavage activity of Pol II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22396529", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 454, "text": "The amino and carboxyl regions of C11 are homologous to domains of the pol II subunit Rpb9p, and the pol II elongation and RNA cleavage factor, TFIIS, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21450810", "endSection": "abstract" } ] }, { "body": "Which is the transcriptome of RNA polymerase III?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28228471", "http://www.ncbi.nlm.nih.gov/pubmed/14634212", "http://www.ncbi.nlm.nih.gov/pubmed/17977614" ], "ideal_answer": [ "RNA polymerase III (Pol III) transcribes a limited set of short genes in eukaryotes producing abundant small RNAs, mostly tRNA. The originally defined yeast Pol III transcriptome appears to be expanding owing to the application of new methods. Newly identified Pol III transcripts include small nucleolar RNAs, microRNAs, short interspersed nuclear element-encoded or tRNA-derived RNAs and novel classes of ncRNA that can display significant sequence complementarity to protein-coding genes and might thus regulate their expression." ], "type": "summary", "id": "5a87e95461bb38fb2400000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "RNA polymerase III (Pol III) transcribes a limited set of short genes in eukaryotes producing abundant small RNAs, mostly tRNA. The originally defined yeast Pol III transcriptome appears to be expanding owing to the application of new methods. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28228471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The role of RNA polymerase (Pol) III in eukaryotic transcription is commonly thought of as being restricted to a small set of highly expressed, housekeeping non-protein-coding (nc)RNA genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17977614", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 668, "text": " Newly identified Pol III transcripts include small nucleolar RNAs, microRNAs, short interspersed nuclear element-encoded or tRNA-derived RNAs and novel classes of ncRNA that can display significant sequence complementarity to protein-coding genes and might thus regulate their expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17977614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "RNA polymerase III (Pol III) transcribes small untranslated RNAs, such as tRNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14634212", "endSection": "abstract" } ] }, { "body": "How many PML isoforms exist in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23028697", "http://www.ncbi.nlm.nih.gov/pubmed/15107834", "http://www.ncbi.nlm.nih.gov/pubmed/25772236", "http://www.ncbi.nlm.nih.gov/pubmed/21172801", "http://www.ncbi.nlm.nih.gov/pubmed/24190887", "http://www.ncbi.nlm.nih.gov/pubmed/9658103", "http://www.ncbi.nlm.nih.gov/pubmed/22773875", "http://www.ncbi.nlm.nih.gov/pubmed/23734343" ], "ideal_answer": [ "PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene.", "The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene." ], "exact_answer": [ "7, designated I to VII", "I-VII" ], "type": "factoid", "id": "593fe5c270f9fc6f0f000021", "snippets": [ { "offsetInBeginSection": 928, "offsetInEndSection": 1091, "text": "The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9658103", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 829, "text": "Using a panel of different PML isoforms, we demonstrate specific co-localization between the E6 proteins and PML isoforms I-IV, but not with PML isoforms V and VI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15107834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21172801", "endSection": "title" }, { "offsetInBeginSection": 524, "offsetInEndSection": 696, "text": " We report that individual expression of PML isoforms I and II partially reverses the increase in ICP0-null mutant HSV-1 plaque formation that occurs in PML-depleted cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21172801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028697", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1024, "text": "Using a bioluminescence resonance energy transfer (BRET) assay in living cells, we found that As\u2082O\u2083 enhanced the SUMOylation and interaction with RNF4 of nuclear PML isoforms (I to VI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028697", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 345, "text": "PML is the structural component of PML nuclear bodies and has several nuclear splice isoforms that share a common N-terminal region but differ in their C termini.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773875", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 417, "text": "Several PML isoforms are generated from a single PML gene by alternative splicing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23734343", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 443, "text": "Six major PML isoforms are expressed as a result of alternative splicing, each of which encodes a unique C-terminal region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24190887", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 515, "text": " However, the biochemical consequences and oncogenic alterations of PML-associated E1B-55K by SUMO-dependent PML-IV and PML-V interaction have so far remained elusive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25772236", "endSection": "abstract" } ] }, { "body": "Do cephalopods use RNA editing less frequently than other species?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25775132", "http://www.ncbi.nlm.nih.gov/pubmed/28855414", "http://www.ncbi.nlm.nih.gov/pubmed/29048557", "http://www.ncbi.nlm.nih.gov/pubmed/26268193", "http://www.ncbi.nlm.nih.gov/pubmed/28388405", "http://www.ncbi.nlm.nih.gov/pubmed/24205087" ], "ideal_answer": [ "Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions. ", "No. Extensive messenger RNA editing generates transcript and protein diversity in cephalopod genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions", "Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions" ], "exact_answer": "no", "type": "yesno", "id": "58e8a2fc3e8b6dc87c00000c", "snippets": [ { "offsetInBeginSection": 1017, "offsetInEndSection": 1237, "text": "Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268193", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 491, "text": "By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29048557", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 476, "text": "We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of\u00a0thousands of evolutionarily conserved sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28388405", "endSection": "abstract" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1280, "text": "Even for the subset of RNA editing sites shared by deeply divergent cephalopod lineages, the primary effect of nuclear editing is an increase-not a decrease-in protein divergence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28855414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268193", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1419, "text": "We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268193", "endSection": "abstract" }, { "offsetInBeginSection": 1552, "offsetInEndSection": 1838, "text": "Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268193", "endSection": "abstract" } ] }, { "body": "Is there an RNAi drug being developed to treat amyloidosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28893208" ], "ideal_answer": [ "Yes, patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis." ], "exact_answer": "yes", "type": "yesno", "id": "5a7357e63b9d13c708000001", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 240, "text": "Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28893208", "endSection": "abstract" } ] }, { "body": "Which receptor does GDF15 bind?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28846099" ], "ideal_answer": [ "GDF15 binds specifically to GDNF family receptor \u03b1-like (GFRAL)" ], "exact_answer": [ "GDNF family receptor \u03b1-like (GFRAL)" ], "type": "factoid", "id": "5a7d6287faa1ab7d2e00001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846099", "endSection": "title" }, { "offsetInBeginSection": 229, "offsetInEndSection": 459, "text": "Here we show that GDF15 binds specifically to GDNF family receptor \u03b1-like (GFRAL) with high affinity, and that GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF15 stimulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846099", "endSection": "abstract" } ] }, { "body": "Is there an association between carcinoid syndrome and mitral valve disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7453210", "http://www.ncbi.nlm.nih.gov/pubmed/11568027", "http://www.ncbi.nlm.nih.gov/pubmed/22364692", "http://www.ncbi.nlm.nih.gov/pubmed/8131775", "http://www.ncbi.nlm.nih.gov/pubmed/26564596", "http://www.ncbi.nlm.nih.gov/pubmed/7236050", "http://www.ncbi.nlm.nih.gov/pubmed/261962" ], "ideal_answer": [ "Yes, mitral valve damage was reported in patients with carcinoid syndrome." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001244", "http://www.disease-ontology.org/api/metadata/DOID:8600" ], "type": "yesno", "id": "5a67a550b750ff4455000009", "snippets": [ { "offsetInBeginSection": 831, "offsetInEndSection": 1076, "text": "Other concomitant operations included mitral valve procedure (11%), aortic valve procedure (9%), patent foramen ovale or atrial septal defect closure (23%), cardiac metastasectomies or biopsy (4%), and simultaneous coronary artery bypass (11%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26564596", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 994, "text": "High circulating serotonin (carcinoid syndrome) and serotoninergic drugs are known to cause valvulopathy that shares pathologic features with DMVD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22364692", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1054, "text": "Surgery included tricuspid valve replacement in all patients, pulmonary valve replacement in 3 and valvectomy in 7, mitral valve replacement in 6 and repair in 1, aortic valve replacement in 4 and repair in 2, CABG in 2, and patent foramen ovale closure in 5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11568027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "We report two observations of significant left heart involvement in patients with the carcinoid syndrome assessed by transthoracic and transoesophageal echocardiography. Echocardiographic lesions of this kind have only been reported twice. In the present cases, there was mitral involvement with mitral regurgitation in one case and a mitro-aortic involvement with mitral and aortic regurgitation in the other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8131775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "An observation of carcinoid syndrome in a woman of 47 suffering from malignant carcinoid of the ileum with metastases into the liver and right ovary is described. The clinical picture included diarrhea, heat waves, bronchospasms, hypertension, hyperserotoninemia, affection of the mitral valve and left atrium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7236050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "A case of carcinoid syndrome, stemming from a tumor of the large intestine with hepatic metastases, is reported. Clinical features included cardiac disease with triple valvular lesion: tricuspid insufficiency with stenosis, pulmonary artery stenosis and mitral insufficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/261962", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 994, "text": "High circulating serotonin (carcinoid syndrome) and serotoninergic drugs are known to cause valvulopathy that shares pathologic features with DMVD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22364692", "endSection": "abstract" } ] }, { "body": "How many of the human PML isoforms are cytosolic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9658103", "http://www.ncbi.nlm.nih.gov/pubmed/24190887" ], "ideal_answer": [ "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not the PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. ", "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. ", "Using a system in which only a single EYFP-linked PML isoform is expressed, PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not", "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not", "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do notThe PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1.", "The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not. ", "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not the PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1." ], "exact_answer": [ "3", "three" ], "type": "factoid", "id": "593fe7f970f9fc6f0f000022", "snippets": [ { "offsetInBeginSection": 444, "offsetInEndSection": 656, "text": "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24190887", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1092, "text": "The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9658103", "endSection": "abstract" } ] }, { "body": "Which tendons are affected in the Dequervain's tenosynovitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28765477", "http://www.ncbi.nlm.nih.gov/pubmed/3488531", "http://www.ncbi.nlm.nih.gov/pubmed/26007263" ], "ideal_answer": [ "DeQuervain's tenosynovitis is a common cause of radial-sided wrist pain. Symptoms result from a narrow first dorsal compartment and associated tendinosis of the enclosed extensor pollicis brevis and/or abductor pollicis longus." ], "exact_answer": [ [ "extensor pollicis brevis" ], [ "abductor pollicis longus" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D013710" ], "type": "list", "id": "5a68ff52b750ff445500001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "DeQuervain's tenosynovitis is a common cause of radial-sided wrist pain. Symptoms result from a narrow first dorsal compartment and associated tendinosis of the enclosed extensor pollicis brevis and/or abductor pollicis longus (APL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28765477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "DeQuervain's disease of the first dorsal compartment of the wrist, is a common wrist pathology, pain results from resisted gliding of the abductor pollicis longus and the extensor pollicis brevis tendon in the fibroosseous canal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26007263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "DeQuervain tenosynovitis, which involves the abductor pollicis longus and extensor pollicis brevis tendons, is much more common in women than men and is due to repetitive movements of the hand such as grasping and twisting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3488531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "DeQuervain tenosynovitis, which involves the abductor pollicis longus and extensor pollicis brevis tendons, is much more common in women than men and is due to repetitive movements of the hand such as grasping and twisting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3488531", "endSection": "abstract" } ] }, { "body": "Are there RNAi approaches considered for the treatment of kidney injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27009268" ], "ideal_answer": [ "Yes, RNAi approaches are being considered for the treatment of kidney injury." ], "exact_answer": "yes", "type": "yesno", "id": "5a74a4be0384be9551000004", "snippets": [ { "offsetInBeginSection": 278, "offsetInEndSection": 487, "text": "Herein, we describe ammonium-functionalized carbon nanotube (fCNT)-mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009268", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 845, "text": "fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, includingTrp53,Mep1b,Ctr1, andEGFP A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009268", "endSection": "abstract" }, { "offsetInBeginSection": 1462, "offsetInEndSection": 1647, "text": "The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009268", "endSection": "abstract" } ] }, { "body": "What does davunetide do to microtubules?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24210139" ], "ideal_answer": [ "Davunetide or NAP is a microtubule-stabilizer." ], "exact_answer": [ "Stabilizes", "Protects" ], "type": "factoid", "id": "5a7d4721faa1ab7d2e000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Microtubule-stabilizing peptides and small molecules protecting axonal transport and brain function: focus on davunetide (NAP).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24210139", "endSection": "title" }, { "offsetInBeginSection": 224, "offsetInEndSection": 425, "text": "We have recently described the effects of NAP in neurodegenerative disorders, and we now review the beneficial effects of NAP and other microtubule-stabilizing agents on impairments in axonal transport", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24210139", "endSection": "abstract" } ] }, { "body": "Is propranolol used for treatment of infantile hemangioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24505868", "http://www.ncbi.nlm.nih.gov/pubmed/27813086", "http://www.ncbi.nlm.nih.gov/pubmed/27473874", "http://www.ncbi.nlm.nih.gov/pubmed/27756073", "http://www.ncbi.nlm.nih.gov/pubmed/24557492", "http://www.ncbi.nlm.nih.gov/pubmed/21385205", "http://www.ncbi.nlm.nih.gov/pubmed/26400030", "http://www.ncbi.nlm.nih.gov/pubmed/21853649", "http://www.ncbi.nlm.nih.gov/pubmed/20071038", "http://www.ncbi.nlm.nih.gov/pubmed/22299307", "http://www.ncbi.nlm.nih.gov/pubmed/21115582", "http://www.ncbi.nlm.nih.gov/pubmed/27737446", "http://www.ncbi.nlm.nih.gov/pubmed/23812512", "http://www.ncbi.nlm.nih.gov/pubmed/22503260", "http://www.ncbi.nlm.nih.gov/pubmed/21837992", "http://www.ncbi.nlm.nih.gov/pubmed/27068061", "http://www.ncbi.nlm.nih.gov/pubmed/24346925", "http://www.ncbi.nlm.nih.gov/pubmed/25511837" ], "ideal_answer": [ "Yes, propranolol is becoming the treatment of choice for complicated infantile hemangioma." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D006391", "https://meshb.nlm.nih.gov/record/ui?ui=D013812", "http://www.biosemantics.org/jochem#4275197", "https://meshb.nlm.nih.gov/record/ui?ui=D011433" ], "type": "yesno", "id": "5a67a72fb750ff445500000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Low-dose propranolol for infantile hemangioma of the head and neck: Analysis of 23 consecutive patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27473874", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "BACKGROUND: More and more infantile hemangiomas (IH) are being treated with propranolol, but the effectiveness, dosage, and treatment course are still in dispute.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27473874", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1299, "text": "CONCLUSIONS: Low-dose propranolol appears to be effective and safe for IH, especially for those patients previously treated with corticosteroid and who had no response or severe side-effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27473874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Cardiovascular Profile of Propranolol after Multiple Dosing in Infantile Hemangioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756073", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Propranolol is becoming the treatment of choice for complicated infantile hemangioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756073", "endSection": "abstract" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1207, "text": "In conclusion, propranolol 2 mg/kg of body weight daily causes a statistically though not clinically relevant decrease in blood pressure and heart rate in cardially healthy infants affected by infantile hemangioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Importance: Propranolol hydrochloride has become the primary medical treatment for problematic infantile hemangioma; however, the expression of propranolol's target receptors during growth, involution, and treatment of hemangioma remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27737446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND: Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. Propranolol is an effective drug in treating IH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27813086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Ultrasonography as an objective tool for assessment of infantile hemangioma treatment with propranolol.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27813086", "endSection": "title" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1195, "text": "CONCLUSION: Ultrasonographic measurements contribute to demonstrate tumor regression and IH response to propranolol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27813086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Propranolol treatment was recently reported to be successful for the management of severe infantile hemangioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21115582", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 984, "text": "We conclude that the initial use of propranolol as the sole treatment for infantile airway hemangioma is promising.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20071038", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 244, "text": "Propranolol has been proposed for the treatment of infantile hemangiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24505868", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 92, "text": "Propranolol therapy is changing the treatment paradigm for infantile hemangioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24557492", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 181, "text": "Propranolol has been successfully used recently in a limited number of children with Infantile hemangioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24346925", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 244, "text": "Propranolol has been proposed for the treatment of infantile hemangiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24505868", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1038, "text": "CONCLUSIONS This is the first report of successful therapy of an intracranial infantile hemangioma with propranolol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27068061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "PURPOSE The successful use of nadolol as an alternative to propranolol therapy in three cases of infantile hemangioma is reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25511837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Propranolol has been used successfully in a limited number of children with infantile hemangiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21385205", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1228, "text": "CONCLUSIONS High-dose Propranolol is very effective in the treatment of infantile hemangioma with minor side effects and short disease period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21837992", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 830, "text": "Propranolol is novel and safe medication for treatment of infantile hemangioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22299307", "endSection": "abstract" }, { "offsetInBeginSection": 1623, "offsetInEndSection": 1824, "text": "Propranolol is the only Food and Drug Administration approved therapy for treatment of patients with this vascular anomaly and should be considered first-line therapy for genital infantile hemangiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26400030", "endSection": "abstract" }, { "offsetInBeginSection": 1384, "offsetInEndSection": 1472, "text": "CONCLUSION Propranolol may be a promising therapeutic modality for infantile hemangioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503260", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 370, "text": "Propranolol, which is often used to treat cutaneous infantile hemangiomas, is not currently standard treatment for intracranial infantile hemangiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27068061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Preliminary results of propranolol treatment for patients with infantile hemangioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21853649", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Propranolol therapy is changing the treatment paradigm for infantile hemangioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24557492", "endSection": "abstract" }, { "offsetInBeginSection": 1450, "offsetInEndSection": 1535, "text": "Propranolol should be considered as a first-line treatment of infantile hemangiomas..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23812512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Propranolol, a non-selective beta-blocker, has recently been introduced as a treatment for infantile hemangiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21853649", "endSection": "abstract" } ] }, { "body": "Can the CEP290 gene mutations be targeted by AAV-mediated gene therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28109959" ], "ideal_answer": [ "The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy." ], "exact_answer": "no", "type": "yesno", "id": "5a75fec383b0d9ea6600000b", "snippets": [ { "offsetInBeginSection": 278, "offsetInEndSection": 396, "text": "The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28109959", "endSection": "abstract" } ] }, { "body": "Which proteins are controlling sterol metabolism in S. cerevisiae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8491706", "http://www.ncbi.nlm.nih.gov/pubmed/10734216", "http://www.ncbi.nlm.nih.gov/pubmed/16096648", "http://www.ncbi.nlm.nih.gov/pubmed/9559263", "http://www.ncbi.nlm.nih.gov/pubmed/1779707", "http://www.ncbi.nlm.nih.gov/pubmed/18390649", "http://www.ncbi.nlm.nih.gov/pubmed/12697649", "http://www.ncbi.nlm.nih.gov/pubmed/23567752" ], "ideal_answer": [ "The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans", "UCP2 and its major targets ERG11, ERG2, NCP1 as well as Osh1p-Osh7p", "Sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae. Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans. The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport. Northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets . Taken together, our results indicate that Upc2p is a key regulator of ergosterol metabolism. ", "The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p included 12 genes involved in ergosterol biosynthesis to better understand Upc2p function in C. albicans, we used genomewide location profiling to identify the transcriptional targets of Upc2p in vivo. Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae. They also suggest that Upc2p may contribute to azole resistance by regulating the expression of drug efflux pump-encoding genes in addition to ergosterol metabolism. Overrepresented functional groups of genes whose promoters were bound by Upc2p is a key regulator of ergosterol metabolism. We have taken advantage of this property to study the regulation of the Delta8-Delta7-sterol isomerase-encoding ERG2 gene in an ergosterol auxotrophic mutant devoid of squalene-synthase activity. Ergosterol starvation leads to an 8-16-fold increase in ERG2 gene expression. ", "Sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae. Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans. The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport. Northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets . Taken together, our results indicate that Upc2p is a key regulator of ergosterol metabolism. To better understand Upc2p function in C. albicans, we used genomewide location profiling to identify the transcriptional targets of Upc2p in vivo. Overrepresented functional groups of genes whose promoters were bound by Upc2p included 12 genes involved in ergosterol biosynthesis . They also suggest that Upc2p may contribute to azole resistance by regulating the expression of drug efflux pump-encoding genes in addition to ergosterol biosynthesis genes. We have taken advantage of this property to study the regulation of the Delta8-Delta7-sterol isomerase-encoding ERG2 gene in an ergosterol auxotrophic mutant devoid of squalene-synthase activity. ", "The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets ( ERG11, MDR1, CDR1, YOR1, SUT1, SMF12, and CBP1 ).Taken together, our results indicate that upc2p is a key regulator of ergosterol metabolism.Overrepresented functional groups of genes whose promoters were bound by upc2p included 12 genes involved in ergosterol biosynthesis ( ncp1, erg11, erg2, and others ) to better understand upc2p function in c. albicans, we used genomewide location profiling to identify the transcriptional targets of upc2p in vivo.Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in candida albicans sterol metabolism and erg2 gene regulation in the yeast saccharomyces cerevisiae.We have taken advantage of this property to study the regulation of the delta8-delta7-sterol isomerase-encoding erg2 gene expression.Ergosterol starvation leads to an 8-16-fold increase in ERG2 gene expression." ], "exact_answer": [ [ "ERG2" ], [ "UCP2" ], [ "Osh1p" ], [ "Osh7p" ], [ "ERG11" ], [ "NCP1" ] ], "type": "list", "id": "590c740d70f9fc6f0f00001d", "snippets": [ { "offsetInBeginSection": 110, "offsetInEndSection": 306, "text": "We have taken advantage of this property to study the regulation of the Delta8-Delta7-sterol isomerase-encoding ERG2 gene in an ergosterol auxotrophic mutant devoid of squalene-synthase activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10734216", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 383, "text": "Ergosterol starvation leads to an 8-16-fold increase in ERG2 gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10734216", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16096648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10734216", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Genomewide location analysis of Candida albicans Upc2p, a regulator of sterol metabolism and azole drug resistance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390649", "endSection": "title" }, { "offsetInBeginSection": 154, "offsetInEndSection": 301, "text": "To better understand Upc2p function in C. albicans, we used genomewide location profiling to identify the transcriptional targets of Upc2p in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390649", "endSection": "abstract" }, { "offsetInBeginSection": 1594, "offsetInEndSection": 1861, "text": " Taken together, our results indicate that Upc2p is a key regulator of ergosterol metabolism. They also suggest that Upc2p may contribute to azole resistance by regulating the expression of drug efflux pump-encoding genes in addition to ergosterol biosynthesis genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390649", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1266, "text": "Northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets (ERG11, MDR1, CDR1, YOR1, SUT1, SMF12, and CBP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390649", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 656, "text": " Overrepresented functional groups of genes whose promoters were bound by Upc2p included 12 genes involved in ergosterol biosynthesis (NCP1, ERG11, ERG2, and others)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390649", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1075, "text": "Cell wall maintenance genes TIR4 and CCW12, sterol metabolism gene UPC2, small molecule transport genes AUS1 and YHK8, and stress response gene CUP1-1 were expressed at a level at least 2.5-fold higher than the expression level found in 9763S.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12697649", "endSection": "abstract" } ] }, { "body": "Which enzymes are responsible for base J creation in Trypanosoma brucei?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25064607", "http://www.ncbi.nlm.nih.gov/pubmed/19136460", "http://www.ncbi.nlm.nih.gov/pubmed/20215442", "http://www.ncbi.nlm.nih.gov/pubmed/17706299", "http://www.ncbi.nlm.nih.gov/pubmed/24891501" ], "ideal_answer": [ "The base is synthesized in a two-step pathway. Initially, a thymidine residue in DNA is hydroxylated by a thymidine hydroxylase (TH). This intermediate (HOMedU) is then glucosylated to form base J. Two proteins involved in J synthesis, JBP1 (J binding protein 1) and JBP2, contain a putative TH domain related to the family of Fe(2+)/2-oxoglutarate-dependent hydroxylases. JBP2 is a chromatin re-modeling protein that induces de novo J-synthesis, allowing JBP1, a J-DNA binding protein, to stimulate additional J-synthesis. A recent computational screen identified a possible candidate for the base J-associated glucosyltransferase (JGT) in trypanosomatid genomes.", "JBP2 and JBP1", "The deletion of both alleles of JGT from the genome of Trypanosoma brucei generates a cell line that completely lacks base J. We conclude that JBP2 and JBP1 are the TH enzymes involved in J biosynthesis. -d-glucopyranosyloxymethyluracil . The base is synthesized in a two-step pathway. Synthesis of the modified thymine base, beta-d-glucosyl-hydroxymethyluracil or J, within telomeric DNA of Trypanosoma brucei correlates with the bloodstream form specific epigenetic silencing of telomeric variant surface glycoprotein genes involved in antigenic variation. Two thymidine hydroxylases differentially regulate the formation of glucosylated DNA at regions flanking polymerase II polycistronic transcription units throughout the genome of Trypanosoma brucei. A recent computational screen identified a possible candidate for the base J-associated glucosyltransferase in trypanosomatid genomes. This intermediate is then glucosylated to form base J. Here we discuss the regulation of hmU and base J formation in the trypanosome genome by JGT and base J-binding protein. Chromosome-internal J deposition is primarily mediated by JBP1, whereas JBP2-stimulated J deposition at the telomeric regions. Two proteins involved in J synthesis, JBP1 /2-oxoglutarate-dependent hydroxylases. JBP2 and JBP1 are capable of stimulating de novo J-synthesis. ", "We have previously characterized two thymidine-hydroxylases (TH), JBP1 and JBP2, which regulate J-biosynthesis.JBP2 is a chromatin re-modeling protein that induces de novo J-synthesis, allowing JBP1, a J-DNA binding protein, to stimulate additional J-synthesis.Chromosome-internal J deposition is primarily mediated by JBP1, whereas JBP2-stimulated J deposition at the telomeric regions.Here we show that mutation of key residues in the TH domain of JBP2 ablate its ability to induce de novo J synthesis.JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes.Here we discuss the regulation of hmU and base J formation in the trypanosome genome by JGT and base J-binding protein.The deletion of both alleles of JGT from the genome of Trypanosoma brucei generates a cell line that completely lacks base JWe have recently proposed a model in which chromatin remodeling by a SWI2/SNF2-like protein (JBP2) regulates the developmental and de novo site-specific localization of J synthesis within bloodstream form trypanosome DNA." ], "exact_answer": [ [ "JBP1" ], [ "JBP2" ], [ "JGT" ] ], "type": "list", "id": "5925227670f9fc6f0f000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Synthesis of the modified thymine base, beta-d-glucosyl-hydroxymethyluracil or J, within telomeric DNA of Trypanosoma brucei correlates with the bloodstream form specific epigenetic silencing of telomeric variant surface glycoprotein genes involved in antigenic variation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17706299", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 645, "text": " We have recently proposed a model in which chromatin remodeling by a SWI2/SNF2-like protein (JBP2) regulates the developmental and de novo site-specific localization of J synthesis within bloodstream form trypanosome DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17706299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19136460", "endSection": "title" }, { "offsetInBeginSection": 262, "offsetInEndSection": 634, "text": "The base is synthesized in a two-step pathway. Initially, a thymidine residue in DNA is hydroxylated by a thymidine hydroxylase (TH). This intermediate (HOMedU) is then glucosylated to form base J. Two proteins involved in J synthesis, JBP1 (J binding protein 1) and JBP2, contain a putative TH domain related to the family of Fe(2+)/2-oxoglutarate-dependent hydroxylases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19136460", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 861, "text": "Here we show that mutation of key residues in the TH domain of JBP2 ablate its ability to induce de novo J synthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19136460", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1271, "text": " We conclude that JBP2 and JBP1 are the TH enzymes involved in J biosynthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19136460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Two thymidine hydroxylases differentially regulate the formation of glucosylated DNA at regions flanking polymerase II polycistronic transcription units throughout the genome of Trypanosoma brucei.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20215442", "endSection": "title" }, { "offsetInBeginSection": 113, "offsetInEndSection": 224, "text": "We have previously characterized two thymidine-hydroxylases (TH), JBP1 and JBP2, which regulate J-biosynthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20215442", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 375, "text": "JBP2 is a chromatin re-modeling protein that induces de novo J-synthesis, allowing JBP1, a J-DNA binding protein, to stimulate additional J-synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20215442", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 461, "text": "JBP2 and JBP1 are capable of stimulating de novo J-synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20215442", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 870, "text": "Chromosome-internal J deposition is primarily mediated by JBP1, whereas JBP2-stimulated J deposition at the telomeric regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20215442", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 262, "text": "\u03b2-d-glucopyranosyloxymethyluracil (base J) synthesis is initiated by the JBP1/2 enzymes that hydroxylate thymine, forming 5-hydroxymethyluracil (hmU)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891501", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 474, "text": "A recent computational screen identified a possible candidate for the base J-associated glucosyltransferase (JGT) in trypanosomatid genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891501", "endSection": "abstract" }, { "offsetInBeginSection": 1450, "offsetInEndSection": 1569, "text": "Here we discuss the regulation of hmU and base J formation in the trypanosome genome by JGT and base J-binding protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891501", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 597, "text": "The thymidine hydroxylases (JPB1 and JBP2) that catalyze the first step have been characterized, but the identity of the glucosyltransferase catalyzing the second step has proven elusive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25064607", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 840, "text": " The deletion of both alleles of JGT from the genome of Trypanosoma brucei generates a cell line that completely lacks base J", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891501", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 841, "text": "The deletion of both alleles of JGT from the genome of Trypanosoma brucei generates a cell line that completely lacks base J.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891501", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 263, "text": "\u03b2-d-glucopyranosyloxymethyluracil (base J) synthesis is initiated by the JBP1/2 enzymes that hydroxylate thymine, forming 5-hydroxymethyluracil (hmU).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891501", "endSection": "abstract" } ] }, { "body": "Which method for subsampling of NGS reads requires only gene counts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18818371", "http://www.ncbi.nlm.nih.gov/pubmed/26830453", "http://www.ncbi.nlm.nih.gov/pubmed/27402900", "http://www.ncbi.nlm.nih.gov/pubmed/24192834", "http://www.ncbi.nlm.nih.gov/pubmed/25189781", "http://www.ncbi.nlm.nih.gov/pubmed/23056304" ], "ideal_answer": [ "SamExploreR : exploring reproducibility and robustness of RNA-seq results based on SAM files.We introduce the subseq r package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth required to inform a broad range of functional and evolutionary studies.Our methods are broadly applicable for polymorphism discovery in moderate to large genomes even at highly diverged loci, and we established by subsampling the illumina sbs coverage depth related questions for the experimental design.SubSeq : determining appropriate sequencing depth through efficient read subsampling.", "Our methods are broadly applicable for polymorphism discovery in moderate to large genomes even at highly diverged loci, and we established by subsampling the Illumina SBS coverage depth required to inform a broad range of functional and evolutionary studies. We introduce the subSeq R package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth", "The subSeq R package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth", "We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models . We introduce the subSeq R package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth. Interestingly, after subsampling to the same coverage for GSNAP and TopHat, we find that both mappers have similar performance, implying that the advantage of TopHat is mainly an artifact of the lower coverage. " ], "exact_answer": [ "subSeq" ], "type": "factoid", "id": "5a39453d966455904c000006", "snippets": [ { "offsetInBeginSection": 1178, "offsetInEndSection": 1437, "text": "Our methods are broadly applicable for polymorphism discovery in moderate to large genomes even at highly diverged loci, and we established by subsampling the Illumina SBS coverage depth required to inform a broad range of functional and evolutionary studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18818371", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 910, "text": "Interestingly, after subsampling to the same coverage for GSNAP and TopHat, we find that both mappers have similar performance, implying that the advantage of TopHat is mainly an artifact of the lower coverage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23056304", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 1061, "text": " By subsampling sequence reads, we found that when using four-fold biological replication, 6 million reads per condition achieved 96% power to detect a two-fold change (or more) at a 5% false discovery rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24192834", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 885, "text": "We introduce the subSeq R package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "subSeq: determining appropriate sequencing depth through efficient read subsampling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189781", "endSection": "title" }, { "offsetInBeginSection": 458, "offsetInEndSection": 688, "text": "We introduce an R package called samExploreR that allows the subsampling (m out of n bootstraping) of short-reads based on SAM files facilitating the investigation of sequencing depth related questions for the experimental design.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27402900", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 827, "text": "We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models (unsupervised and supervised).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26830453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "samExploreR: exploring reproducibility and robustness of RNA-seq results based on SAM files.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27402900", "endSection": "title" }, { "offsetInBeginSection": 420, "offsetInEndSection": 732, "text": "By randomly sampling lower depths from a sequencing experiment and determining where the saturation of power and accuracy occurs, one can determine what the most useful depth should be for future experiments, and furthermore, confirm whether an existing experiment had sufficient depth to justify its conclusions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189781", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 410, "text": "One complication is that the power and accuracy of such experiments depend substantially on the number of reads sequenced, so it is important and challenging to determine the optimal read depth for an experiment or to verify whether one has adequate depth in an existing experiment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189781", "endSection": "abstract" } ] }, { "body": "Which topoisomerase is essential in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16651657", "http://www.ncbi.nlm.nih.gov/pubmed/23935120", "http://www.ncbi.nlm.nih.gov/pubmed/7932731", "http://www.ncbi.nlm.nih.gov/pubmed/2840207", "http://www.ncbi.nlm.nih.gov/pubmed/1332607", "http://www.ncbi.nlm.nih.gov/pubmed/18570880", "http://www.ncbi.nlm.nih.gov/pubmed/6090122", "http://www.ncbi.nlm.nih.gov/pubmed/2842762", "http://www.ncbi.nlm.nih.gov/pubmed/21767457", "http://www.ncbi.nlm.nih.gov/pubmed/6323017", "http://www.ncbi.nlm.nih.gov/pubmed/12888496", "http://www.ncbi.nlm.nih.gov/pubmed/1316274" ], "ideal_answer": [ "Eukaryotic DNA topoisomerase II is an abundant nuclear enzyme that is essential for cell proliferation. Yeast DNA topoisomerase II is encoded by a single-copy, essential gene.", "Yeast DNA topoisomerase II is encoded by a single-copy, essential gene. Disruption of one copy of the gene in a diploid yeast creates a recessive lethal mutation, indicating that the single DNA topoisomerase II gene of yeast has an essential function.", "Yeast DNA topoisomerase II is encoded by a single-copy, essential gene." ], "exact_answer": [ "topoisomerase II", "topo II" ], "type": "factoid", "id": "5a4e50b242878bf97d000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Yeast DNA topoisomerase II is encoded by a single-copy, essential gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6323017", "endSection": "title" }, { "offsetInBeginSection": 687, "offsetInEndSection": 866, "text": "Disruption of one copy of the gene in a diploid yeast creates a recessive lethal mutation, indicating that the single DNA topoisomerase II gene of yeast has an essential function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6323017", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1278, "text": "The type II topoisomerase may have an essential role in the compaction and/or segregation of chromosomes during the nuclear division but also complement the defect of the type I enzyme whose major function is the maintenance of chromatin organization throughout the cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6090122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Since DNA topoisomerase II (EC 5.99.1.3) is an essential enzyme in yeast, heterologous topoisomerase II gene expression in yeast cells can provide a system for analyzing the structure and function of topoisomerase II genes from other species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2842762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Eukaryotic DNA topoisomerase II is an abundant nuclear enzyme that is essential for cell proliferation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7932731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Topoisomerase II is a ubiquitous enzyme that removes knots and tangles from the genetic material by generating transient double-strand DNA breaks. While the enzyme cannot perform its essential cellular functions without cleaving DNA, this scission activity is inherently dangerous to chromosomal integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12888496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Topoisomerase II (Topo II) performs topological modifications on double-stranded DNA molecules that are essential for chromosome condensation, resolution, and segregation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16651657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Type II topoisomerases are essential for resolving topologically entwined double-stranded DNA. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18570880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "DNA topoisomerases are specialized nuclear enzymes that perform topological modifications on double-stranded DNA (dsDNA) and hence are essential for DNA metabolism such as replication, transcription, recombination, condensation and segregation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21767457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Eukaryotic topoisomerase II (topo II) is the essential decatenase of newly replicated chromosomes and the main relaxase of nucleosomal DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23935120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "The decatenation activity of DNA topoisomerase II is essential for viability as eukaryotic cells traverse mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1316274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Studies with yeast DNA topoisomerase mutants indicate that neither topoisomerase I nor II appears to be essential for transcription by RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2840207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The gene encoding topoisomerase II in yeast is unique and essential, required for both mitotic and meiotic proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1332607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The decatenation activity of DNA topoisomerase II is essential for viability as eukaryotic cells traverse mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1316274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Yeast DNA topoisomerase II is encoded by a single-copy, essential gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6323017", "endSection": "title" }, { "offsetInBeginSection": 687, "offsetInEndSection": 867, "text": "Disruption of one copy of the gene in a diploid yeast creates a recessive lethal mutation, indicating that the single DNA topoisomerase II gene of yeast has an essential function..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6323017", "endSection": "abstract" } ] }, { "body": "What is the genetic basis of Ohdo syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24123922", "http://www.ncbi.nlm.nih.gov/pubmed/18798845", "http://www.ncbi.nlm.nih.gov/pubmed/26338144", "http://www.ncbi.nlm.nih.gov/pubmed/24039113", "http://www.ncbi.nlm.nih.gov/pubmed/24715367", "http://www.ncbi.nlm.nih.gov/pubmed/23395478" ], "ideal_answer": [ "MED12 cause X-linked Ohdo syndromeIn", "Mutations in MED12 cause X-linked Ohdo syndrome", "Mutations in MED12 cause X-linked Ohdo syndrome The occurrence of three different hemizygous missense mutations in three unrelated families affected by Ohdo syndrome MKB type shows that mutations in MED12 are the underlying cause of this X-linked form of Ohdo syndrome.", "Mutations in MED12 cause X-linked Ohdo syndrome In the two families, MED12 missense mutations (c.3443G>A [p.Arg1148His] or c.3493T>C [p.Ser1165Pro]) segregating with the phenotype were identified.", "FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type, have been described as distinct syndromes with overlapping non-specific features and different missense mutations of the MED12 gene have been reported in all of them. Mutations in MED12 cause X-linked Ohdo syndrome", "The occurrence of three different hemizygous missense mutations in three unrelated families affected by Ohdo syndrome MKB type shows that mutations in MED12 are the underlying cause of this X-linked form of Ohdo syndrome.", "Mutations in MED12 cause X-linked Ohdo syndrome FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type, have been described as distinct syndromes with overlapping non-specific features and different missense mutations of the MED12 gene have been reported in all of them.", "MED12" ], "exact_answer": [ "mutations in MED12" ], "type": "factoid", "id": "58f89eb270f9fc6f0f00001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Mutations in MED12 cause X-linked Ohdo syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395478", "endSection": "title" }, { "offsetInBeginSection": 521, "offsetInEndSection": 860, "text": "In the two families, MED12 missense mutations (c.3443G>A [p.Arg1148His] or c.3493T>C [p.Ser1165Pro]) segregating with the phenotype were identified. Upon subsequent analysis of an additional cohort of nine simplex male individuals with Ohdo syndrome, one additional de novo missense change (c.5185C>A [p.His1729Asn]) in MED12 was detected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395478", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1082, "text": "The occurrence of three different hemizygous missense mutations in three unrelated families affected by Ohdo syndrome MKB type shows that mutations in MED12 are the underlying cause of this X-linked form of Ohdo syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type, have been described as distinct syndromes with overlapping non-specific features and different missense mutations of the MED12 gene have been reported in all of them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039113", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 548, "text": "Parallel sequencing of all X-chromosome exons identified a frameshift mutation (c.5898dupC) of MED12.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039113", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1619, "text": "The severe degree of ID in male patients, as well as variable cognitive impairment in heterozygous females suggests that the duplication observed in the present family may have a more severe effect on MED12 function than missense mutations. In a cognitively impaired male from this family, who also presented with tall stature and dysmorphism and did not have the MED12 mutation, a 600-kb duplication at 17p13.3 including the YWHAE gene, was found in a mosaic state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039113", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 1061, "text": " To date, these conditions include Opitz-Kaveggia (FG) syndrome, Lujan syndrome, Ohdo syndrome (Maat-Kievit-Brunner type, or OSMKB), and one large family with profound X-linked intellectual disability due to a novel c.5898insC frameshift mutation that unlike the other three syndromes, resulted in affected female carriers and truncation of the MED12 protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24123922", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1427, "text": "This case lends credence to the evolving theory that the subtypes of Ohdo, and perhaps other MED12 disorders, reflect a spectrum of characteristics, rather than distinct syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338144", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 647, "text": "MED12 [MIM *300188] (mediator complex subunit 12) mutations have been linked to numerous XLID syndromes, including Lujan, FG, and Ohdo, and MED12 is included in many XLID panels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338144", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 580, "text": "Finally, direct sequencing of MED12, the gene mutated in Opitz-Kaveggia syndrome, Lujan-Fryns syndrome and X-linked Ohdo syndrome identified in the two sibs the missense mutation c.3443G>A (p.Arg1148His) inherited from the mother.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24715367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Mutations in MED12 cause X-linked Ohdo syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395478", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Beyond Ohdo syndrome: A familial missense mutation broadens the MED12 spectrum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338144", "endSection": "title" } ] }, { "body": "Which drugs were tested in the KEYNOTE-006 study?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27896938", "http://www.ncbi.nlm.nih.gov/pubmed/25891173", "http://www.ncbi.nlm.nih.gov/pubmed/28987768", "http://www.ncbi.nlm.nih.gov/pubmed/28822576", "http://www.ncbi.nlm.nih.gov/pubmed/26846323", "http://www.ncbi.nlm.nih.gov/pubmed/28964438", "http://www.ncbi.nlm.nih.gov/pubmed/28125365" ], "ideal_answer": [ "KEYNOTE-006 study compared pembrolizumab versus ipilimumab for advanced melanoma." ], "exact_answer": [ [ "pembrolizumab" ], [ "ipilimumab" ] ], "type": "list", "id": "5a737b483b9d13c70800000b", "snippets": [ { "offsetInBeginSection": 700, "offsetInEndSection": 884, "text": "The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent randomized phase 3 study (KEYNOTE-006) that compared pembrolizumab and ipilimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28125365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822576", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "BACKGROUND: Interim analyses of the phase 3 KEYNOTE-006 study showed superior overall and progression-free survival of pembrolizumab versus ipilimumab in patients with advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822576", "endSection": "abstract" }, { "offsetInBeginSection": 3062, "offsetInEndSection": 3284, "text": "INTERPRETATION: Substantiating the results of the interim analyses of KEYNOTE-006, pembrolizumab continued to provide superior overall survival versus ipilimumab, with no difference between pembrolizumab dosing schedules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "OBJECTIVE: Report results of patient-reported health-related quality of life (HRQoL) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28987768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Patient-reported outcomes in KEYNOTE-006, a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28987768", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "Pembrolizumab (Keytruda(\u00ae)) is a humanized monoclonal antibody against programmed death receptor-1 (PD-1), a key immunoinhibitory checkpoint protein implicated in down-regulating anti-tumour immune responses. This intravenous drug is indicated for the treatment of advanced (unresectable or metastatic) melanoma, on the basis of its clinical benefit in this setting in the phase I KEYNOTE 001 trial (expansion cohorts) and the phase II and III trials, KEYNOTE 002 and 006.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26846323", "endSection": "abstract" }, { "offsetInBeginSection": 1740, "offsetInEndSection": 2019, "text": "CONCLUSIONS: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. (Funded by Merck Sharp&Dohme; KEYNOTE-006 ClinicalTrials.gov number, NCT01866319.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25891173", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 186, "text": "Interim analyses of the phase 3 KEYNOTE-006 study showed superior overall and progression-free survival of pembrolizumab versus ipilimumab in patients with advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822576", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 218, "text": "Report results of patient-reported health-related quality of life (HRQoL) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28987768", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 886, "text": "The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent randomized phase 3 study (KEYNOTE-006) that compared pembrolizumab and ipilimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28125365", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 506, "text": "A cost-effectiveness model was developed to analyze the costs and consequences of treatment with pembrolizumab compared to treatment with ipilimumab in patients with advanced melanoma not previously treated with ipilimumab. The model was parameterized by using data from a head-to-head phase III randomized clinical trial, KEYNOTE-006.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28964438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "BACKGROUND Interim analyses of the phase 3 KEYNOTE-006 study showed superior overall and progression-free survival of pembrolizumab versus ipilimumab in patients with advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "OBJECTIVE Report results of patient-reported health-related quality of life (HRQoL) and symptoms from phase III KEYNOTE-006 study of pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28987768", "endSection": "abstract" }, { "offsetInBeginSection": 3079, "offsetInEndSection": 3299, "text": "INTERPRETATION Substantiating the results of the interim analyses of KEYNOTE-006, pembrolizumab continued to provide superior overall survival versus ipilimumab, with no difference between pembrolizumab dosing schedules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822576", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 889, "text": "The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent randomized phase 3 study (KEYNOTE-006) that compared pembrolizumab and ipilimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28125365", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 1197, "text": "In the trials with active comparator arms, pembrolizumab regimens significantly improved progression-free survival (PFS), overall survival (OS) and overall response rates (ORR) relative to ipilimumab in ipilimumab-na\u00efve patients (KEYNOTE 006), and significantly improved PFS and ORR, but not OS (although OS data are immature), relative to chemotherapy in ipilimumab-refractory patients, who had also received BRAF/MEK inhibitor therapy if BRAF-mutation positive (KEYNOTE 002).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26846323", "endSection": "abstract" } ] }, { "body": "What is the purpose of the FRAX scale?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22630782", "http://www.ncbi.nlm.nih.gov/pubmed/22492479", "http://www.ncbi.nlm.nih.gov/pubmed/25771422", "http://www.ncbi.nlm.nih.gov/pubmed/22489911", "http://www.ncbi.nlm.nih.gov/pubmed/26474615", "http://www.ncbi.nlm.nih.gov/pubmed/24369275", "http://www.ncbi.nlm.nih.gov/pubmed/28004298", "http://www.ncbi.nlm.nih.gov/pubmed/27647529", "http://www.ncbi.nlm.nih.gov/pubmed/25186156", "http://www.ncbi.nlm.nih.gov/pubmed/21899835", "http://www.ncbi.nlm.nih.gov/pubmed/28660987", "http://www.ncbi.nlm.nih.gov/pubmed/23203733", "http://www.ncbi.nlm.nih.gov/pubmed/21198706", "http://www.ncbi.nlm.nih.gov/pubmed/28429557" ], "ideal_answer": [ "The FRAX score (The WHO Fracture Risk Assessment Tool), is a free web-based clinical scale assessing the 10-year probability of major osteoporotic fracture risk and need for lifestyle advice/reassurance, dual X-ray absorptiometry (DEXA) scanning or preventive treatment." ], "type": "summary", "id": "5a6f8baeb750ff4455000057", "snippets": [ { "offsetInBeginSection": 1339, "offsetInEndSection": 1500, "text": "RESULTS: The DA was acceptable to subjects, but 17\u00a0% of the patients in the decision aid arm incorrectly entered their T-scores into FRAX-based risk calculator. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27647529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Comparing self-perceived and estimated fracture risk by FRAX\u00ae of women with osteoporosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004298", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "In this study, we compared subjective fracture risks of Hungarian women with osteoporosis to FRAX\u00ae-based estimates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004298", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 598, "text": "PURPOSE: The main objectives were to explore associations between self-perceived 10-year fracture risks of women with osteoporosis (OP) and their risks calculated by the FRAX\u00ae algorithm and to identify determinants of the underestimation of risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004298", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 1012, "text": "The development of absolute fracture risk (AFR) algorithms, such as FRAX\u00ae and the Garvan absolute fracture risk calculator, to predict risk of fracture over a given time (usually 10\u00a0years) aims to incorporate non-BMD risk factors into the clinical assessment. FRAX\u00ae has been shown to be useful to assess fracture risk in CKD but may underestimate fracture risk in advanced CKD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28429557", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 258, "text": "THE GOAL: was an evaluation of the correlation between 10-year risk of death from CVD and 10-year bone fracture risk (FRAX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28660987", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "OBJECTIVE: To verify the fracture risk assessment tool (FRAX) to estimate the probability of osteoporotic fracture in patients with rheumatoid arthritis (RA) with or without bone mineral density (BMD), and identify associated risk factors of osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26474615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Can paramedics use FRAX (the WHO Fracture Risk Assessment Tool) to help GPs improve future fracture risk in patients who fall?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25186156", "endSection": "title" }, { "offsetInBeginSection": 486, "offsetInEndSection": 707, "text": "Paramedics who attend to patients who have fallen may be well placed to assess future fracture risk, using the Fracture Risk Assessment Tool (FRAX) and communicate that information directly to general practitioners (GPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25186156", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 952, "text": "Key changes are revision of the criteria for initiation of pharmaceutical treatment, along with an introduction of the fracture risk factors used in FRAX\u00ae, inclusion of newly developed drugs, and revision of the recommendation grades for pharmaceutical treatment of osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24369275", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 198, "text": "The Fracture Risk Assessment Tool (FRAX) was developed to estimate the risk of fracture in the general population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22489911", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 208, "text": "FRAX provides 10-year probability of major fractures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22630782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The WHO Fracture Risk Assessment Tool (FRAX; http://www.shef.ac.uk/FRAX) estimates the 10-year probability of major osteoporotic fracture. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492479", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 779, "text": "One of the key changes is revision of the criteria for initiation of pharmacological treatment, along with an introduction of the fracture risk factors used in FRAX\u00ae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23203733", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 923, "text": "The principal variable was the likelihood of fracture evaluated with the FRAX\u00ae tool for the Spanish population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21899835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Application of the WHO fracture risk assessment tool (FRAX) to predict need for DEXA scanning and treatment in patients with inflammatory bowel disease at risk of osteoporosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21198706", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 414, "text": "he FRAX score, developed by the WHO, is a free web-based clinical scale assessing the 10-year fracture risk and need for lifestyle advice/reassurance, dual X-ray absorptiometry (DEXA) scanning or preventive treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21198706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "PURPOSE: The WHO fracture risk prediction tool (FRAX\u00ae) utilises clinical risk factors to estimate the probability of fracture over a 10-year period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25771422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "PURPOSE The WHO fracture risk prediction tool (FRAX\u00ae) utilises clinical risk factors to estimate the probability of fracture over a 10-year period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25771422", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 413, "text": "The FRAX score, developed by the WHO, is a free web-based clinical scale assessing the 10-year fracture risk and need for lifestyle advice/reassurance, dual X-ray absorptiometry (DEXA) scanning or preventive treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21198706", "endSection": "abstract" } ] }, { "body": "Are mutations in the nf1 gene associated with memory?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19475561", "http://www.ncbi.nlm.nih.gov/pubmed/17581973" ], "ideal_answer": [ "Yes, distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation." ], "exact_answer": "yes", "type": "yesno", "id": "5a87efa961bb38fb2400000e", "snippets": [ { "offsetInBeginSection": 326, "offsetInEndSection": 423, "text": "We hypothesized that NF1 mutations disturb the expression of genes important for memory formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19475561", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 734, "text": "Our previous work has shown that defective cAMP signaling leads to the learning phenotype in Drosophila Nf1 mutants. In the present report, our experiments showed that in addition to learning, long-term memory was also abolished in Nf1 mutants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17581973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17581973", "endSection": "title" } ] }, { "body": "Has Cas9 gene editing the potential to correct inhereted hearing loss?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26876963", "http://www.ncbi.nlm.nih.gov/pubmed/26915297", "http://www.ncbi.nlm.nih.gov/pubmed/27013738", "http://www.ncbi.nlm.nih.gov/pubmed/25987504" ], "ideal_answer": [ "CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo.\r\nThe genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation." ], "type": "summary", "id": "5a886da58cb19eca6b000004", "snippets": [ { "offsetInBeginSection": 1400, "offsetInEndSection": 1569, "text": " CRISPR/Cas9-mediated HDR has been successfully utilised to efficiently correct the Cdh23 (ahl) allele in C57BL/6NTac mice, and rescue the associated auditory phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26876963", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 881, "text": "We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26915297", "endSection": "abstract" }, { "offsetInBeginSection": 1025, "offsetInEndSection": 1152, "text": " Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in\u00a0vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25987504", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 360, "text": "The genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27013738", "endSection": "abstract" }, { "offsetInBeginSection": 1636, "offsetInEndSection": 1872, "text": "the present study might provide further insight into the pathogenesis of sensorineural hearing loss and facilitate the development of therapeutic strategies against monogenic disease through the genetic repair of patient-specific iPSCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27013738", "endSection": "abstract" } ] }, { "body": "How may CTCF mediate splicing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "http://www.ncbi.nlm.nih.gov/pubmed/24534946", "http://www.ncbi.nlm.nih.gov/pubmed/26154016", "http://www.ncbi.nlm.nih.gov/pubmed/22976956", "http://www.ncbi.nlm.nih.gov/pubmed/24657531", "http://www.ncbi.nlm.nih.gov/pubmed/26929370", "http://www.ncbi.nlm.nih.gov/pubmed/27083996", "http://www.ncbi.nlm.nih.gov/pubmed/25934638", "http://www.ncbi.nlm.nih.gov/pubmed/25837375", "http://www.ncbi.nlm.nih.gov/pubmed/26711177" ], "ideal_answer": [ "Two different mechanisms convey DNA methylation information into the regulation of alternative splicing. The first involves modulation of the elongation rate of RNA polymerase II (Pol II) by CCCTC-binding factor (CTCF) and methyl-CpG binding protein 2 (MeCP2); the second involves the formation of a protein bridge by heterochromatin protein 1 (HP1) that recruits splicing factors onto transcribed alternative exons.", "CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Intragenic 5-methylcytosine and CTCF mediate opposing effects on pre-mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5-methylcytosine evicts CTCF, leading to exon exclusion.", "CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.Here we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wideCTCF also functions in RNA polymerase II regulation and in doing so can influence co-transcriptional splicing events.CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing.In particular, the CCCTC-binding factor (CTCF), the Argonaute protein AGO1, and members of the heterochromatin protein 1 (HP1) family have been implicated in the regulation of splicing associated with chromatin and the elongation of RNAPII.Furthermore, we found mutations in the splicing factor SFPQ and in the nonclassic regulators of mRNA processing CTCF and RAD21.However, there was no correlation between the KTS+/KTS- splicing variants of WT1 and the methylation status of the CpGs of the CTCF binding site." ], "type": "summary", "id": "5a43a933966455904c00000b", "snippets": [ { "offsetInBeginSection": 328, "offsetInEndSection": 744, "text": "Two different mechanisms convey DNA methylation information into the regulation of alternative splicing. The first involves modulation of the elongation rate of RNA polymerase II (Pol II) by CCCTC-binding factor (CTCF) and methyl-CpG binding protein 2 (MeCP2); the second involves the formation of a protein bridge by heterochromatin protein 1 (HP1) that recruits splicing factors onto transcribed alternative exons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25837375", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1084, "text": "Furthermore, we found mutations in the splicing factor SFPQ and in the nonclassic regulators of mRNA processing CTCF and RAD21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22976956", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1257, "text": " We show that CTCF bound to HTLV-1 acts as an enhancer blocker, regulates HTLV-1 mRNA splicing, and forms long-distance interactions with flanking host chromatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26929370", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1573, "text": " Many CTCF sites are also involved in other functions such as modulation of RNA splicing and specific regulation of gene expression, and the relationship between these activities and loop formation is another unanswered question that should keep investigators occupied for some time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "TET-catalyzed oxidation of intragenic 5-methylcytosine regulates CTCF-dependent alternative splicing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26711177", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Intragenic 5-methylcytosine and CTCF mediate opposing effects on pre-mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5-methylcytosine evicts CTCF, leading to exon exclusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26711177", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 515, "text": "Here, we reveal the methylcytosine dioxygenases TET1 and TET2 as active regulators of CTCF-mediated alternative splicing through conversion of 5-methylcytosine to its oxidation derivatives. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26711177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A chromatin code for alternative splicing involving a putative association between CTCF and HP1\u03b1 proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934638", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 534, "text": "Recent experiments have suggested a new complex network of splicing regulation involving chromatin, transcription and multiple protein factors. In particular, the CCCTC-binding factor (CTCF), the Argonaute protein AGO1, and members of the heterochromatin protein 1 (HP1) family have been implicated in the regulation of splicing associated with chromatin and the elongation of RNAPII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934638", "endSection": "abstract" }, { "offsetInBeginSection": 1716, "offsetInEndSection": 2017, "text": "Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1\u03b1 and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1\u03b1 and AGO1 in chromatin-related splicing regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934638", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 709, "text": "CTCF also functions in RNA polymerase II regulation and in doing so can influence co-transcriptional splicing events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26154016", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 252, "text": " CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24657531", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 923, "text": "However, there was no correlation between the KTS+/KTS- splicing variants of WT1 and the methylation status of the CpGs of the CTCF binding site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24534946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "endSection": "title" }, { "offsetInBeginSection": 565, "offsetInEndSection": 827, "text": "Here we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "endSection": "abstract" } ] }, { "body": "Is ACI-35 a passive vaccine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27485083" ], "ideal_answer": [ "No, ACI-35 is an active vaccine." ], "exact_answer": "no", "type": "yesno", "id": "5a7d50d0faa1ab7d2e000016", "snippets": [ { "offsetInBeginSection": 392, "offsetInEndSection": 519, "text": "Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27485083", "endSection": "abstract" } ] }, { "body": "Which main ribotype of Clostridium difficile is responsible of the recent outbreak?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27751937", "http://www.ncbi.nlm.nih.gov/pubmed/28169013", "http://www.ncbi.nlm.nih.gov/pubmed/26341328", "http://www.ncbi.nlm.nih.gov/pubmed/27411304", "http://www.ncbi.nlm.nih.gov/pubmed/28592343", "http://www.ncbi.nlm.nih.gov/pubmed/28782647", "http://www.ncbi.nlm.nih.gov/pubmed/28396132", "http://www.ncbi.nlm.nih.gov/pubmed/28501926", "http://www.ncbi.nlm.nih.gov/pubmed/27533048" ], "ideal_answer": [ "The outbreak of the hypervirulent strain belonging to ribotype 027 has increased the incidence and severity of CDI in some countries." ], "exact_answer": [ "Ribotype 027" ], "type": "factoid", "id": "5a87d73861bb38fb2400000b", "snippets": [ { "offsetInBeginSection": 113, "offsetInEndSection": 248, "text": " From May 2013 to May 2014, an outbreak of C.\u00a0difficile ribotype 027 occurred in a Dutch tertiary care hospital, involving 72 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28169013", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 467, "text": " During this period, 70 endemic cases of CDI occurred as well as 78 cases of CDI related to an outbreak of C. difficile ribotype 027", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28592343", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 314, "text": "The outbreak of the hypervirulent strain belonging to ribotype 027 has increased the incidence and severity of CDI in some countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28396132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "An outbreak of Clostridium difficile PCR ribotype 027 in Spain: risk factors for recurrence and a novel treatment strategy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28501926", "endSection": "title" }, { "offsetInBeginSection": 97, "offsetInEndSection": 296, "text": " The aim of this study was to determine whether early recurrence risk was higher after infection with ribotype 027 (outbreak strain) compared with infection with endemic strain types of C.\u00a0difficile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28782647", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 170, "text": "The rapid spread of Clostridium difficile NAP1/BI/027 (C. difficile 027) has become one of the leading threats of healthcare-associated infections worldwide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27411304", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "An outbreak of Clostridium difficile ribotype 027 infection (CDI) occurred at an university hospital, involving 19 departments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27533048", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 516, "text": "The majority of strains from Bosnia and Herzegovina and Serbia belonged to PCR ribotype 027 (65.8%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27751937", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1472, "text": "Ribotype 027 is highly prevalent in Germany, but its infections are restricted to older patients, while absent in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26341328", "endSection": "abstract" } ] }, { "body": "What is the function of the TFIIS transcriptional factor (Dst1) in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22544605", "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "http://www.ncbi.nlm.nih.gov/pubmed/16648643", "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "http://www.ncbi.nlm.nih.gov/pubmed/21761155", "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "http://www.ncbi.nlm.nih.gov/pubmed/15359273" ], "ideal_answer": [ "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II.", "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II. Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS. It is proposed that TFIIS and the Spt8-containing form of SAGA co-operate to rescue RNA polymerase II from unproductive elongation complexes, and that the Cdk8 module temporarily blocks transcription during transcript cleavage.", "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II. Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS. It is proposed that TFIIS and the Spt8-containing form of SAGA co-operate to rescue RNA polymerase II from unproductive elongation complexes, and that the Cdk8 module temporarily blocks transcription during transcript cleavage. TFIIS promotes the intrinsic ability of RNA polymerase II to cleave the 3'-end of the newly synthesized RNA. TFIIS and Rpb9 are essential when the cells are challenged with microtubule-destabilizing drugs;", "Transcription factor IIS (TFIIS) stimulates RNA cleavage by RNA polymerase II by allowing backtracked enzymes to resume transcription elongation. TFIIS promotes the intrinsic ability of RNA polymerase II to cleave the 3'-end of the newly synthesized RNA. Recent studies revealed that TFIIS has also a role in Pol II transcription initiation. TFIIS is required under stress conditions and that TFIIS is important for the transition between initiation and elongation in vivo.", "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II. Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS. TFIIS and Pol III occupancies correlated well genome-wide on this novel class of targets. These data provide strong in vivo and in vitro evidence in favor of a role of TFIIS as a general Pol III transcription factor. Transcription factor IIS (TFIIS) stimulates RNA cleavage by RNA polymerase II by allowing backtracked enzymes to resume transcription elongation." ], "type": "summary", "id": "5a003e0a966455904c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15359273", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 500, "text": "Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15359273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15359273", "endSection": "title" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1189, "text": "It is proposed that TFIIS and the Spt8-containing form of SAGA co-operate to rescue RNA polymerase II from unproductive elongation complexes, and that the Cdk8 module temporarily blocks transcription during transcript cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15359273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "TFIIS promotes the intrinsic ability of RNA polymerase II to cleave the 3'-end of the newly synthesized RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 842, "text": "TFIIS and Rpb9 are essential when the cells are challenged with microtubule-destabilizing drugs;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 402, "text": "While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1271, "text": "We propose that TFIIS is required under stress conditions and that TFIIS is important for the transition between initiation and elongation in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The eukaryotic transcript elongation factor TFIIS is encoded by a nonessential gene, PPR2, in Saccharomyces cerevisiae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16648643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Genome-wide location analysis reveals a role of TFIIS in RNA polymerase III transcription.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "TFIIS is a transcription elongation factor that stimulates transcript cleavage activity of arrested RNA polymerase II (Pol II)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 214, "text": "Recent studies revealed that TFIIS has also a role in Pol II transcription initiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 714, "text": " TFIIS and Pol III occupancies correlated well genome-wide on this novel class of targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1071, "text": "These data provide strong in vivo and in vitro evidence in favor of a role of TFIIS as a general Pol III transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Transcription factor IIS (TFIIS) stimulates RNA cleavage by RNA polymerase II by allowing backtracked enzymes to resume transcription elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "TFIIS is required for the balanced expression of the genes encoding ribosomal components under transcriptional stress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544605", "endSection": "title" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1249, "text": "We discuss the effect of transcriptional stress on ribosome biogenesis and propose that TFIIS contributes to prevent a transcriptional imbalance between rDNA and RP genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544605", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 384, "text": "Here, we investigated the role of nascent transcript cleavage stimulation activity on the maintenance of transcriptional fidelity in yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "TFIIS is a transcription elongation factor that stimulates transcript cleavage activity of arrested RNA polymerase II (Pol II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 817, "text": "A mild but systematic increase in RNA polymerase occupancy and a strict dependency on the transcript cleavage factor TFIIS (Dst1) also suggest a slower rate of translocation or higher probability of transcriptional stalling in this mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21761155", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1287, "text": "Also, a DST1 and RPB9 double mutant had more severe transcriptional fidelity defect compared with the DST1 gene deletion mutant, suggesting that Rpb9 maintains transcriptional fidelity via two mechanisms, enhancement of S-II dependent cleavage stimulation and S-II independent function(s)..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "endSection": "abstract" } ] }, { "body": "Is DNA methylation correlated with nucleosome occupancy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26484155", "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "http://www.ncbi.nlm.nih.gov/pubmed/22960375", "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "http://www.ncbi.nlm.nih.gov/pubmed/26305225", "http://www.ncbi.nlm.nih.gov/pubmed/24419148", "http://www.ncbi.nlm.nih.gov/pubmed/23085715", "http://www.ncbi.nlm.nih.gov/pubmed/24812327", "http://www.ncbi.nlm.nih.gov/pubmed/23408854", "http://www.ncbi.nlm.nih.gov/pubmed/24916973", "http://www.ncbi.nlm.nih.gov/pubmed/21835883", "http://www.ncbi.nlm.nih.gov/pubmed/23686312", "http://www.ncbi.nlm.nih.gov/pubmed/23502848", "http://www.ncbi.nlm.nih.gov/pubmed/28413449" ], "ideal_answer": [ "DNA methylation can determine nucleosome positioning. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters. DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key determinant of gene expression. In order to systematically evaluate potential diversities among CGIs and ultimately to illuminate the link between diversity of CGIs and their epigenetic variation, we analyzed the nucleotide-resolution DNA methylation maps of multiple cellular origins. Using this global approach, we observe the dependency of nucleosome occupancy upon the DNA methylation status. Exonic DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels. Transcription, histone modifications, and DNA methylation alter this \"ground state\" by having distinct effects on both nucleosome positioning and occupancy. ", "Human promoters containing a CpG island tend to remain nucleosome-free as well as methylation-free.Exonic dna methylation can determine nucleosome positioning.In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy.Using this global approach, we observe the dependency of nucleosome occupancy upon the dna methylation seems to function together with exonic nucleosomes and h3k36me3 for the proper splicing of transcripts with different expression levels.In order to systematically evaluate potential diversities among cgis and ultimately to illuminate the link between diversity of cgis and their epigenetic variation, we analyzed the nucleotide-resolution dna methylation status.Transcription, histone modifications, and dna methylation determines nucleosome occupancy in the 5'-cpg islands of tumor suppressor genes.Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key determinant of gene expression.Using this global approach, we analyzed the nucleotide-resolution dna methylation maps ( methylomes ) of multiple cellular origins.Dna methylation alter this \"ground state\" by having distinct effects on both nucleosome positioning.", "In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy.Nucleosome-free regions were observed only in promoters containing a CpG islandHere I show that CpG islands were associated not only with methylation-free promoters but also with nucleosome-free promoters.In contrast to the methylation-and nucleosome-free states of CpG-island promoters, exons were densely methylated at CpGs and packaged into nucleosomes.I also found that nucleosomes, DNA methylation, and H3K36me3 marked the exons of transcripts with low, medium, and high gene expression levels, respectively.DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes.DNA methylation can determine nucleosome positioning.DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter.The mostly unmethylated CpG islands have reduced nucleosome occupancy and are enriched in cell type-independent binding sites for CTCF.Three positions at the splice sites show high CpG abundance and accompany elevated nucleosome occupancy in a leveled GC architecture.", "Here I show that CpG islands were associated not only with methylation-free promoters but also with nucleosome-free promoters. Nucleosome-free regions were observed only in promoters containing a CpG island In contrast to the methylation-and nucleosome-free states of CpG-island promoters, exons were densely methylated at CpGs and packaged into nucleosomes. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy.", "Using this global approach, we observe the dependency of nucleosome occupancy upon the DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation maps of multiple cellular origins. Transcription, histone modifications, and DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes. Exonic DNA methylation can determine nucleosome positioning. In order to systematically evaluate potential diversities among CGIs and ultimately to illuminate the link between diversity of CGIs and their epigenetic variation, we analyzed the nucleotide-resolution DNA methylation and nucleosome occupancy. Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key determinant of gene expression levels. Human promoters containing a CpG island tend to remain nucleosome-free as well as methylation-free. In contrast, exons demonstrate a high degree of methylation status. DNA methylation at CTCF regions that is not present at promoters. ", "Recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter. Using a novel bioinformatics pipeline a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters can be shown. The induction of DNA hypomethylation events by genetic (DNMT1/DNMT3B deficient cells) or drug (a DNA demethylating agent) approaches is associated with the eviction of nucleosomes from previously hypermethylated CpG islands of tumor suppressor genes.", "DNA methylation can determine nucleosome positioning. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters. DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. ", "In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters. ", "yes" ], "exact_answer": "yes", "type": "yesno", "id": "5a43a214966455904c000009", "snippets": [ { "offsetInBeginSection": 464, "offsetInEndSection": 590, "text": "Here I show that CpG islands were associated not only with methylation-free promoters but also with nucleosome-free promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 670, "text": "Nucleosome-free regions were observed only in promoters containing a CpG island", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "endSection": "abstract" }, { "offsetInBeginSection": 836, "offsetInEndSection": 987, "text": "In contrast to the methylation-and nucleosome-free states of CpG-island promoters, exons were densely methylated at CpGs and packaged into nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "endSection": "abstract" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1400, "text": "I also found that nucleosomes, DNA methylation, and H3K36me3 marked the exons of transcripts with low, medium, and high gene expression levels, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1512, "text": "Human promoters containing a CpG island tend to remain nucleosome-free as well as methylation-free.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "endSection": "abstract" }, { "offsetInBeginSection": 1513, "offsetInEndSection": 1598, "text": "In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1758, "text": "Exonic DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20602769", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 476, "text": "Supporting such an association, recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21835883", "endSection": "title" }, { "offsetInBeginSection": 560, "offsetInEndSection": 734, "text": "Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960375", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1429, "text": "Three positions at the splice sites show high CpG abundance and accompany elevated nucleosome occupancy in a leveled GC architecture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23502848", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 600, "text": "The first group has higher nucleosome occupancy on exons than introns, whereas the second group exhibits weak nucleosome marking of exons, suggesting another type of epigenetic marker distinguishes exons from introns when GC content is similar.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23502848", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 377, "text": " DNA methylation can determine nucleosome positioning. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686312", "endSection": "title" }, { "offsetInBeginSection": 466, "offsetInEndSection": 715, "text": "he induction of DNA hypomethylation events by genetic (DNMT1/DNMT3B deficient cells) or drug (a DNA demethylating agent) approaches is associated with the eviction of nucleosomes from previously hypermethylated CpG islands of tumor suppressor genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686312", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1360, "text": "Using this global approach, we observe the dependency of nucleosome occupancy upon the DNA methylation status. Thus, our results suggest that there is a close association between hypermethylated CpG islands and the presence of nucleosomes, such that each of these epigenetic mechanisms can determine the recruitment of the other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686312", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 326, "text": "Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key determinant of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23408854", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1093, "text": "Our results indicate that only a minority of demethylated promoters are associated with nucleosome remodeling, and these could potentially be the epigenetic drivers causing the loss of tumorigenicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23408854", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 356, "text": "with repressed genes often being associated with local DNA hypermethylation and gain of nucleosomes at their promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26484155", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1064, "text": "Transcription, histone modifications, and DNA methylation alter this \"ground state\" by having distinct effects on both nucleosome positioning and occupancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305225", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 644, "text": "In order to systematically evaluate potential diversities among CGIs and ultimately to illuminate the link between diversity of CGIs and their epigenetic variation, we analyzed the nucleotide-resolution DNA methylation maps (methylomes) of multiple cellular origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24419148", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 680, "text": "The mostly unmethylated CpG islands have reduced nucleosome occupancy and are enriched in cell type-independent binding sites for CTCF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24812327", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 948, "text": "In contrast, outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24812327", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1056, "text": "Aberrant acquisition of nucleosomes at enhancer-associated NDRs is associated with hypermethylation and epigenetic silencing marks, and conversely, loss of nucleosomes with demethylation and epigenetic activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916973", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1822, "text": "Prominent exceptions to the correlations between methylated CpG density and nucleosome occupancy include CpG islands marked by H3K27me3 and CpG-poor heterochromatin marked by H3K9me3, and these modifications, along with DNA methylation, distinguish the major silencing mechanisms of the human epigenome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28413449", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 822, "text": "Throughout the genome, nucleosome occupancy was correlated with certain histone methylation or acetylation modifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23085715", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 984, "text": "We further show that the extent of nucleosome depletion at promoters is directly correlated to expression level and can accommodate multiple nucleosomes and provide genome-wide evidence that expressed non-CpG island promoters are nucleosome-depleted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22960375", "endSection": "abstract" } ] }, { "body": "Which R/Bioconductor package has been developed for the analysis of psychiatric disease genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28961763" ], "ideal_answer": [ "PsyGeNET is a knowledge resource on psychiatric diseases and their genes, developed by text mining and curated by domain experts. Psygenet2r is an R package that contains a variety of functions for leveraging PsyGeNET database and facilitating its analysis and interpretation. The package offers different types of queries to the database along with variety of analysis and visualization tools, including the study of the anatomical structures in which the genes are expressed and gaining insight of gene's molecular function. Psygenet2r is especially suited for network medicine analysis of psychiatric disorders.", "psygenet2r" ], "exact_answer": [ "Psygenet2r" ], "type": "factoid", "id": "5a6e2b1bb750ff445500003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "psygenet2r: a R/Bioconductor package for the analysis of psychiatric disease genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961763", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 852, "text": "Psychiatric disorders have a great impact on morbidity and mortality. Genotype-phenotype resources for psychiatric diseases are key to enable the translation of research findings to a better care of patients. PsyGeNET is a knowledge resource on psychiatric diseases and their genes, developed by text mining and curated by domain experts.Results: We present psygenet2r, an R package that contains a variety of functions for leveraging PsyGeNET database and facilitating its analysis and interpretation. The package offers different types of queries to the database along with variety of analysis and visualization tools, including the study of the anatomical structures in which the genes are expressed and gaining insight of gene's molecular function. Psygenet2r is especially suited for network medicine analysis of psychiatric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961763", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 989, "text": "The package is implemented in R and is available under MIT license from Bioconductor ( http://bioconductor.org/packages/release/bioc/html/psygenet2r.html ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961763", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 832, "text": "Psygenet2r is especially suited for network medicine analysis of psychiatric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961763", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 853, "text": "Psygenet2r is especially suited for network medicine analysis of psychiatric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961763", "endSection": "abstract" } ] }, { "body": "Which Janus kinase does decernotinib target?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25762693" ], "ideal_answer": [ "Decernotinib (VX-509) is a potent and selective inhibitor of janus kinase 3 (JAK3)." ], "exact_answer": [ "Janus kinase 3 (JAK3)" ], "type": "factoid", "id": "5a7610af83b0d9ea6600001a", "snippets": [ { "offsetInBeginSection": 506, "offsetInEndSection": 869, "text": "The aim of this study was to evaluate the potency and selectivity of the investigational JAK3 inhibitor VX-509 (decernotinib) [(R)-2-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide]against JAK3 kinase activity and inhibition of JAK3-mediated signaling in vitro and JAK3-dependent physiologic processes in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25762693", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1127, "text": "These results demonstrate that VX-509 potently inhibits JAK3 in enzyme assays (Ki = 2.5 nM + 0.7 nM) and cellular assays dependent on JAK3 activity (IC50 range, 50-170 nM), with limited or no measurable potency against other JAK isotypes or non-JAK kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25762693", "endSection": "abstract" }, { "offsetInBeginSection": 1512, "offsetInEndSection": 1752, "text": "These findings demonstrate that VX-509 is a selective and potent inhibitor of JAK3 in vitro and modulates proinflammatory response in models of immune-mediated diseases, such as collagen-induced arthritis and delayed-type hypersensitivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25762693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "VX-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25762693", "endSection": "title" } ] }, { "body": "What is the genetic basis of the Delayed Sleep-Phase Syndrome (DSPS)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11306557", "http://www.ncbi.nlm.nih.gov/pubmed/12841365", "http://www.ncbi.nlm.nih.gov/pubmed/11763990", "http://www.ncbi.nlm.nih.gov/pubmed/11186112", "http://www.ncbi.nlm.nih.gov/pubmed/15700718", "http://www.ncbi.nlm.nih.gov/pubmed/19708722", "http://www.ncbi.nlm.nih.gov/pubmed/12736803", "http://www.ncbi.nlm.nih.gov/pubmed/10498237" ], "ideal_answer": [ "Circadian gene mutations are also associated with circadian rhythm disorders such as familial advanced sleep phase syndrome, delayed sleep phase syndrome, and non-24-hour sleep-wake syndrome. Possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome. The study investigated the human leucocyte antigen (HLA), types A, B and DR, of 42 patients with delayed sleep phase syndrome (DSPS) and compared the frequencies of the antigens with those in 117 healthy controls. The comparison revealed that the gene frequencies and positivities of HLA-A, -B and -DR, except for DR1, had no significant differences between the patients and controls. The frequency of HLA-DR1 was increased in the DSPS patients as compared with that in the healthy controls (P = 0.0069 in positivity). In human leukocyte antigen (HLA) typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. ", "Circadian gene mutations are also associated with circadian rhythm disorders such as familial advanced sleep phase syndrome, delayed sleep phase syndrome, and non-24-hour sleep-wake syndrome. A possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome has been reported. In human leukocyte antigen (HLA) typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. The data suggest that AA-NAT could be a susceptibility gene for DSPS.", "We studied the association between the AA-NAT gene and delayed sleep phase syndrome . Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it?. Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome . One of the haplotypes was significantly associated with DSPS in our study population. In human leukocyte antigen typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. Polymorphisms in the CLOCK, BMAL1, Per3 and TIMELESS genes have been associated with susceptibility to mood disorder, and single nucleotide polymorphisms and haplotypes in several circadian genes have been observed among those displaying certain circadian phenotypes, including worse mood in the evening, insomnia in mania and early, middle or late insomnia in depression. The Per3 polymorphism correlated significantly with extreme diurnal preference, the longer allele associating with morningness and the shorter allele with eveningness. The frequency of the 129 threonine allele is significantly higher in the patients than in the controls . " ], "type": "summary", "id": "58ede257eda5a57672000010", "snippets": [ { "offsetInBeginSection": 281, "offsetInEndSection": 473, "text": "Circadian gene mutations are also associated with circadian rhythm disorders such as familial advanced sleep phase syndrome, delayed sleep phase syndrome, and non-24-hour sleep-wake syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19708722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10498237", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The study investigated the human leucocyte antigen (HLA), types A, B and DR, of 42 patients with delayed sleep phase syndrome (DSPS) and compared the frequencies of the antigens with those in 117 healthy controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10498237", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 384, "text": "The comparison revealed that the gene frequencies and positivities of HLA-A, -B and -DR, except for DR1, had no significant differences between the patients and controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10498237", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 518, "text": "The frequency of HLA-DR1 was increased in the DSPS patients as compared with that in the healthy controls (P = 0.0069 in positivity).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10498237", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 551, "text": "In human leukocyte antigen (HLA) typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11186112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11306557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11306557", "endSection": "title" }, { "offsetInBeginSection": 686, "offsetInEndSection": 958, "text": "One of the haplotypes was significantly associated with DSPS (Bonferroni's corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11306557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12841365", "endSection": "title" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1976, "text": "Polymorphisms in the CLOCK, BMAL1, Per3 and TIMELESS genes have been associated with susceptibility to mood disorder, and single nucleotide polymorphisms and haplotypes in several circadian genes have been observed among those displaying certain circadian phenotypes, including worse mood in the evening, insomnia in mania and early, middle or late insomnia in depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19708722", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 141, "text": " To investigate the link between extreme diurnal preference, delayed sleep phase syndrome, and a length polymorphism in Per3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12841365", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 682, "text": "The Per3 polymorphism correlated significantly with extreme diurnal preference, the longer allele associating with morningness and the shorter allele with eveningness. The shorter allele was strongly associated with the delayed sleep phase syndrome patients, 75% of whom were homozygous.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12841365", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 686, "text": "We studied the association between the AA-NAT gene and delayed sleep phase syndrome (DSPS). Results indicate that there is a significant difference in allele positivity at the single nucleotide polymorphism involved in an amino acid substitution from alanine to threonine at position 129 between patients with DSPS and healthy controls. The frequency of the 129 threonine allele is significantly higher in the patients than in the controls ( P=0.0029). The data suggest that AA-NAT could be a susceptibility gene for DSPS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736803", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1064, "text": "Our results suggest that latitude has a role in the influence of hPer3 gene polymorphism on delayed sleep-phase syndrome and confirm previous data showing its association with morningness-eveningness tendencies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15700718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15700718", "endSection": "title" } ] }, { "body": "What are jakinibs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26994322", "http://www.ncbi.nlm.nih.gov/pubmed/22819198" ], "ideal_answer": [ "Jakinibs are Janus kinase (JAK) inhibitors. They are considered a new class of kinase inhibitors in cancer and autoimmune disease. Jakinibs can differ substantially in their selectivity against JAKs." ], "type": "summary", "id": "5a76039b83b0d9ea66000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819198", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819198", "endSection": "title" }, { "offsetInBeginSection": 387, "offsetInEndSection": 587, "text": "These receptors rely on Janus family of kinases (Jaks) for signal transduction. Recently the first Jak inhibitor (jakinib) has been approved by the FDA and a second has been recommended for approval. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22819198", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 417, "text": "Recent progress in treating RA has been achieved with janus kinase (JAK) inhibitors (Jakinibs), an orally available disease-modifying anti-rheumatic drug targeting the intracellular kinase JAK and with similar efficacy to biologics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26994322", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 1061, "text": "Given these promising findings, Jakinibs are expected to represent the next generation compounds for treating RA, and a number of Jakinibs are currently in clinical trials. Jakinibs can differ substantially in their selectivity against JAKs; tofacitinib and baricitinib target multiple JAKs, whereas the most recently developed Jakinibs target only a single JAK. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26994322", "endSection": "abstract" } ] }, { "body": "What is the function of the gene MDA5?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28530548", "http://www.ncbi.nlm.nih.gov/pubmed/29117565", "http://www.ncbi.nlm.nih.gov/pubmed/28250012", "http://www.ncbi.nlm.nih.gov/pubmed/29069650", "http://www.ncbi.nlm.nih.gov/pubmed/28374903" ], "ideal_answer": [ "Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein mitochondrial antiviral signaling protein (MAVS) to provide a signal platform for the induction of type I interferon (IFN) and proinflammatory cytokines. The conformational switch of MDA5 causes antiviral defense, but excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases." ], "exact_answer": [ "Sensing of non-self RNAs, especially viral RNA" ], "type": "factoid", "id": "5a88370c61bb38fb24000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28250012", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 647, "text": "The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28530548", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 748, "text": "RNA PRRs are comprised of TLR3, TLR7, TLR8, RIG-I, MDA5, NLRP3, NOD2, and some other minorities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28374903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 616, "text": "Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein mitochondrial antiviral signaling protein (MAVS) to provide a signal platform for the induction of type I interferon (IFN) and proinflammatory cytokines. The conformational switch of MDA5 causes antiviral defense, but excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including melanoma differentiation-associated gene 5 (MDA5) and RIG-I, are crucial for host recognition of non-self RNAs, especially viral RNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29117565", "endSection": "abstract" } ] }, { "body": "Which is the conserved motif of DEAD box proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7731693" ], "ideal_answer": [ "The conserved motif is: Asp(D)-Glu-(E)-Ala(A)-Asp(D)" ], "exact_answer": [ "Asp(D)-Glu-(E)-Ala(A)-Asp(D)" ], "type": "factoid", "id": "5a885daa61bb38fb24000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "DEAD box proteins are putative RNA helicases that have been implicated in cellular processes involving alteration of RNA secondary structure, such as translation initiation and splicing. These proteins share eight conserved amino acid motifs, including Asp(D)-Glu-(E)-Ala(A)-Asp(D) which is part of a more extended motif. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7731693", "endSection": "abstract" } ] }, { "body": "Which individuals show preferential colonization of the Prevotellaceae bacteria in their guts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26216344", "http://www.ncbi.nlm.nih.gov/pubmed/19567577", "http://www.ncbi.nlm.nih.gov/pubmed/19164560", "http://www.ncbi.nlm.nih.gov/pubmed/26207384", "http://www.ncbi.nlm.nih.gov/pubmed/21408168", "http://www.ncbi.nlm.nih.gov/pubmed/25864056", "http://www.ncbi.nlm.nih.gov/pubmed/23548695", "http://www.ncbi.nlm.nih.gov/pubmed/27570628" ], "ideal_answer": [ "Although the distinction of enterotypes as either discrete clusters or a continuum will require additional investigation, numerous studies have demonstrated the co-exclusion of the closely related Prevotellaceae and Bacteroides genera in the gut microbiota of healthy human subjects where Prevotella appears to be a discriminatory taxon for residence in more agrarian societies." ], "exact_answer": [ "members of agrarian societies" ], "type": "factoid", "id": "58ee2515eda5a57672000016", "snippets": [ { "offsetInBeginSection": 138, "offsetInEndSection": 244, "text": "a new member of the Prevotellaceae family that was isolated from stool samples from a 45-year-old patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27570628", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1432, "text": "Using univariate non-parametric statistics, there were no differences regarding alpha or beta diversity between AH8.1 carriers (categories I and II) and non-carriers (categories III and IV), however four different taxa (Prevotellaceae, Clostridium XVIII, Coprococcus, Enterorhabdus) had nominally significant lower abundances in AH8.1 carriers than non-carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26207384", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 887, "text": "The increase in Bacteroidetes was found to be due to an increase in members of the families Bacteroidaceae or Prevotellaceae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25864056", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 675, "text": "Fecal communities clustered into previously described enterotypes distinguished primarily by levels of Bacteroides and Prevotella.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23548695", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1192, "text": "Although the distinction of enterotypes as either discrete clusters or a continuum will require additional investigation, numerous studies have demonstrated the co-exclusion of the closely related Prevotellaceae and Bacteroides genera in the gut microbiota of healthy human subjects where Prevotella appears to be a discriminatory taxon for residence in more agrarian societies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23548695", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 861, "text": "Lachnospiraceae, Ruminococcaceae, Bacteroidaceae, Prevotellaceae, and Rickenellaceae were the predominant families detected in the active microbiota", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21408168", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 918, "text": "Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19164560", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 794, "text": "A comparative sequence analysis revealed that these two species are members of the family 'Prevotellaceae' but are phylogenetically distant (<88% sequence similarity) from the known genera belonging to this family, including Prevotella, Hallela and Xylanibacter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19567577", "endSection": "abstract" } ] }, { "body": "Describe GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28007912" ], "ideal_answer": [ "GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types) is a bioinformatic toolkit for aetiologically connecting diseases and cell type-specific regulatory maps. GARLIC can be used to retrieve potential disease-causative genetic variants overlapping regulatory sequences of interest. Overall, GARLIC can satisfy several important needs within the field of medical genetics, thus potentially assisting in the ultimate goal of uncovering the elusive and complex genetic basis of common human disorders.", "GARLIC is a bioinformatic toolkit for aetiologically connecting diseases and cell type-specific regulatory maps." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D055106", "https://meshb.nlm.nih.gov/record/ui?ui=D004194" ], "type": "summary", "id": "5a6e5df6b750ff445500004e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "GARLIC: a bioinformatic toolkit for aetiologically connecting diseases and cell type-specific regulatory maps.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007912", "endSection": "title" }, { "offsetInBeginSection": 522, "offsetInEndSection": 1312, "text": "Based on emerging evidences suggesting that disease-associated SNPs are frequently found within cell type-specific regulatory sequences, here we present GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types), a user-friendly, multi-purpose software with an associated database and online viewer that, using global maps of cis-regulatory elements, can aetiologically connect human diseases with relevant cell types. Additionally, GARLIC can be used to retrieve potential disease-causative genetic variants overlapping regulatory sequences of interest. Overall, GARLIC can satisfy several important needs within the field of medical genetics, thus potentially assisting in the ultimate goal of uncovering the elusive and complex genetic basis of common human disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007912", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 959, "text": "Based on emerging evidences suggesting that disease-associated SNPs are frequently found within cell type-specific regulatory sequences, here we present GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types), a user-friendly, multi-purpose software with an associated database and online viewer that, using global maps of cis-regulatory elements, can aetiologically connect human diseases with relevant cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007912", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1095, "text": "Additionally, GARLIC can be used to retrieve potential disease-causative genetic variants overlapping regulatory sequences of interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007912", "endSection": "abstract" } ] }, { "body": "How does Dst1 knock-out affect transcription in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "http://www.ncbi.nlm.nih.gov/pubmed/28521214", "http://www.ncbi.nlm.nih.gov/pubmed/24780862", "http://www.ncbi.nlm.nih.gov/pubmed/14690608", "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "http://www.ncbi.nlm.nih.gov/pubmed/16492753", "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "http://www.ncbi.nlm.nih.gov/pubmed/14704159", "http://www.ncbi.nlm.nih.gov/pubmed/15359273" ], "ideal_answer": [ "While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability. We showed that: dst1 and rpb9 mutants have a synthetic growth defective phenotype when combined with fyv4, gim5, htz1, yal011w, ybr231c, soh1, vps71, and vps72 mutants that is exacerbated during germination or at high salt concentrations. In vivo, some dst1 mutants were partly defective in tRNA synthesis and showed a reduced Pol III occupancy at the restrictive temperature.", "While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability." ], "type": "summary", "id": "5a37df1c966455904c000004", "snippets": [ { "offsetInBeginSection": 269, "offsetInEndSection": 402, "text": "While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Genetic interactions of DST1 in Saccharomyces cerevisiae suggest a role of TFIIS in the initiation-elongation transition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "endSection": "title" }, { "offsetInBeginSection": 499, "offsetInEndSection": 742, "text": "We showed that: (1) dst1 and rpb9 mutants have a synthetic growth defective phenotype when combined with fyv4, gim5, htz1, yal011w, ybr231c, soh1, vps71, and vps72 mutants that is exacerbated during germination or at high salt concentrations; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082542", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 652, "text": "Yet we find strong genetic interaction of rpb4\u2206 with mutants in many transcription elongation factors such as Paf1, Spt4, Dst1, Elp3 and Rpb9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24780862", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 852, "text": "In vivo, some dst1 mutants were partly defective in tRNA synthesis and showed a reduced Pol III occupancy at the restrictive temperature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18628399", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 793, "text": " Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts. spt8Delta and dst1Delta mutants were sensitive to nucleotide-depleting drugs and epistatic to null mutants of the RNA polymerase II subunit Rpb9, suggesting that their elongation defects are mediated by Rpb9. rpb9Delta, spt8Delta and dst1Delta were lethal in cells lacking the Rpb4 subunit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15359273", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 845, "text": "Ess1 opposes elongation factors Dst1 and Spt4/5, and overexpression of ESS1 makes cells more sensitive to the elongation inhibitor 6-AU.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14704159", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1286, "text": "Also, a DST1 and RPB9 double mutant had more severe transcriptional fidelity defect compared with the DST1 gene deletion mutant, suggesting that Rpb9 maintains transcriptional fidelity via two mechanisms, enhancement of S-II dependent cleavage stimulation and S-II independent function(s).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1102, "text": "We additionally show that Dst1, a homolog of mammalian transcription elongation factor TFIIS, interferes with NER-dependent repair of AP lesions while suppressing homologous recombination pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28521214", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1205, "text": "Overall, Def1 and Dst1 mediate very different outcomes in response to AP-induced transcription arrest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28521214", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 654, "text": "Yet we find strong genetic interaction of rpb4\u2206 with mutants in many transcription elongation factors such as Paf1, Spt4, Dst1, Elp3 and Rpb9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24780862", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1287, "text": "Also, a DST1 and RPB9 double mutant had more severe transcriptional fidelity defect compared with the DST1 gene deletion mutant, suggesting that Rpb9 maintains transcriptional fidelity via two mechanisms, enhancement of S-II dependent cleavage stimulation and S-II independent function(s)..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17535246", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 542, "text": "However, deletion of DST1, the gene encoding the yeast homolog of TFIIS, had only a small effect on transcriptional fidelity, as determined by this assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16492753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Deletions of three yeast genes, SET2, CDC73, and DST1, involved in transcriptional elongation and/or chromatin metabolism were used in conjunction with genetic array technology to screen approximately 4700 yeast deletions and identify double deletion mutants that produce synthetic growth defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14690608", "endSection": "abstract" } ] }, { "body": "Which drug can be reversed with idarucizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "http://www.ncbi.nlm.nih.gov/pubmed/28416406", "http://www.ncbi.nlm.nih.gov/pubmed/27727040", "http://www.ncbi.nlm.nih.gov/pubmed/27920714", "http://www.ncbi.nlm.nih.gov/pubmed/27625113", "http://www.ncbi.nlm.nih.gov/pubmed/26872887", "http://www.ncbi.nlm.nih.gov/pubmed/28887767", "http://www.ncbi.nlm.nih.gov/pubmed/27224445", "http://www.ncbi.nlm.nih.gov/pubmed/28479184", "http://www.ncbi.nlm.nih.gov/pubmed/26894245", "http://www.ncbi.nlm.nih.gov/pubmed/27268941", "http://www.ncbi.nlm.nih.gov/pubmed/27477871", "http://www.ncbi.nlm.nih.gov/pubmed/27215215", "http://www.ncbi.nlm.nih.gov/pubmed/27568285", "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "http://www.ncbi.nlm.nih.gov/pubmed/25567155", "http://www.ncbi.nlm.nih.gov/pubmed/27317414", "http://www.ncbi.nlm.nih.gov/pubmed/25789661", "http://www.ncbi.nlm.nih.gov/pubmed/27575900", "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "http://www.ncbi.nlm.nih.gov/pubmed/27175894", "http://www.ncbi.nlm.nih.gov/pubmed/27697436" ], "ideal_answer": [ "Idarucizumab is an antibody fragment that specifically reverses dabigatran mediated anticoagulation." ], "exact_answer": [ "dabigatran" ], "type": "factoid", "id": "5a7237672dc08e987e000008", "snippets": [ { "offsetInBeginSection": 774, "offsetInEndSection": 918, "text": "So far only one reversal agent has been approved by the Food and Drug Administration (FDA), idarucizumab for one of the DOACs i.e., dabigatran. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27215215", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1586, "text": " New oral anticoagulants such as apixaban, rivaroxaban, or dabigatran may be preferred to vitamin K antagonists in patients without cancer or renal failure, more so after the development of reversal agents such as idarucizumab and andexanet alfa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27268941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND AND OBJECTIVES: Idarucizumab is an antibody fragment that specifically reverses dabigatran-mediated anticoagulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27317414", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1653, "text": "Idarucizumab resulted in immediate, complete and sustained reversal of dabigatran anticoagulant activity, and was safe and well tolerated in middle-aged, elderly and renally impaired volunteers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27317414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Effect of Age and Renal Function on Idarucizumab Pharmacokinetics and Idarucizumab-Mediated Reversal of Dabigatran Anticoagulant Activity in a Randomized, Double-Blind, Crossover Phase Ib Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27317414", "endSection": "title" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1063, "text": "We also discuss reversal strategies, both specific and nonspecific, for each drug, including the preferential use of idarucizumab for the reversal of dabigatran and two agents, andexanet and ciraparantag, currently under development for the reversal of rivaroxaban, apixaban, and edoxaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27625113", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 340, "text": "Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27727040", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1373, "text": "CONCLUSIONS: The initial data suggest a definite role for idarucizumab in treatment of bleeding associated with dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27727040", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1153, "text": "The administration of 5\u2009g of intravenous idarucizumab promptly and completely reversed the anticoagulant activity of dabigatran as assessed by routine and specific coagulation assays (aPTT from to 75 to 26\u2009s, PT from 26 to 11\u2009s and diluted thrombin time from 92 to 27\u2009s).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27224445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Idarucizumab, a monoclonal antibody fragment that binds dabigatran with high affinity, is in development as a specific antidote for dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25789661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25789661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "To evaluate the role of idarucizumab, a humanized monoclonal antibody fragment, as a specific reversal agent for the anticoagulant activity of dabigatran and to review the pharmacology, pharmacokinetic properties, efficacy, and safety of this agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26894245", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1059, "text": "Dabigatran etexilate is an oral thrombin inhibitor that can be reversed by idarucizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479184", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 569, "text": "In ICH related to dabigatran, anticoagulation can be rapidly reversed with idarucizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887767", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 72, "text": "Idarucizumab is a reversal agent for dabigatran etexilate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479184", "endSection": "abstract" }, { "offsetInBeginSection": 1852, "offsetInEndSection": 1939, "text": "Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1062, "text": "Dabigatran etexilate is an oral thrombin inhibitor that can be reversed by idarucizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "INTRODUCTION Idarucizumab is a reversal agent for dabigatran etexilate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Idarucizumab is a humanized monoclonal antibody fragment for reversal of the anticoagulant effects of dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27575900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Idarucizumab is a monoclonal antibody fragment specifically targeted to dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Idarucizumab is a monoclonal antibody fragment specifically targeted to dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27697436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "BACKGROUND AND OBJECTIVES Idarucizumab is an antibody fragment that specifically reverses dabigatran-mediated anticoagulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27317414", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1174, "text": "Idarucizumab, a monoclonal antibody fragment, directly binds dabigatran etexilate and neutralizes its activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479184", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 406, "text": "Idarucizumab is an antibody fragment that binds dabigatran with high affinity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27224445", "endSection": "abstract" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1326, "text": "CONCLUSION Reversal of dabigatran etexilate using idarucizumab was safe and successful with no recombinant tissue plasminogen activator interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28479184", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 730, "text": "RESULTS Idarucizumab represents a novel treatment option as it is the only humanized, monoclonal antibody fragment that specifically binds to dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26894245", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 574, "text": "In 2015, the humanized monoclonal antibody fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant effects of dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416406", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1197, "text": "Idarucizumab is a specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran, which was recently approved for use in the USA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26872887", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 416, "text": "Idarucizumab, an antibody fragment targeting dabigatran, is the first specific antidote for a NOAC to be approved, but real-world experience is limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27920714", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1076, "text": "Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the effects of the drug on coagulation variables.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Idarucizumab is an antibody fragment that specifically reverses dabigatran-mediated anticoagulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27317414", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 188, "text": "Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "abstract" }, { "offsetInBeginSection": 1734, "offsetInEndSection": 1868, "text": "Idarucizumab also reversed the effects of dabigatran and, unlike PCCs, was not associated with over-correction of thrombin generation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567155", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 400, "text": "Dabigatran etexilate (DE) dose-dependently prolonged diluted thrombin time and tail-vein bleeding time, which were reversed by idarucizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1106, "text": "In this article, we discuss the evidence addressing idarucizumab safety, tolerability and its efficacy for reversing effect of dabigatran..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27477871", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 966, "text": "This was until the recent The Food and Drug Administration approval of idarucizumab, a potential reversal agent for dabigatran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27477871", "endSection": "abstract" }, { "offsetInBeginSection": 2425, "offsetInEndSection": 2809, "text": "Idarucizumab immediately and completely reversed dabigatran-induced anticoagulation in a dose-dependent manner; the mean ratio of day 4 AUEC2-12 to day 3 AUEC2-12 for dTT was 1\u00b701 with placebo, 0\u00b726 with 1 g idarucizumab (74% reduction), 0\u00b706 with 2 g idarucizumab (94% reduction), 0\u00b702 with 4 g idarucizumab (98% reduction), and 0\u00b701 with 5 g plus 2\u00b75 g idarucizumab (99% reduction).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27175894", "endSection": "title" } ] }, { "body": "What is the function of the TMEM132 genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29088312" ], "ideal_answer": [ "The extra-cellular portions of TMEM132 proteins contain five conserved domains including three tandem immunoglobulin domains, and a cohesin domain homologue, the first such domain found in animals. These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton." ], "exact_answer": [ "Cellular adhesion function" ], "type": "factoid", "id": "5a6e472ab750ff4455000048", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "TMEM132: an ancient architecture of cohesin and immunoglobulin domains define a new family of neural adhesion molecules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 868, "text": "Here we show the full domain architecture of human TMEM132 family proteins solved using in-depth sequence and structural analysis. We reveal them to be five previously unappreciated cell adhesion molecules whose domain architecture has an early holozoan origin prior to the emergence of choanoflagellates and metazoa. The extra-cellular portions of TMEM132 proteins contain five conserved domains including three tandem immunoglobulin domains, and a cohesin domain homologue, the first such domain found in animals. These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The molecular functions of TMEM132 genes remain poorly understood and under-investigated despite their mutations associated with non-syndromic hearing loss, panic disorder and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 859, "text": "These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 699, "text": "The extra-cellular portions of TMEM132 proteins contain five conserved domains including three tandem immunoglobulin domains, and a cohesin domain homologue, the first such domain found in animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 867, "text": "These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" } ] }, { "body": "Does DDX54 play a role in DNA damage response?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28596291" ], "ideal_answer": [ "Yes. DDX54, a candidate genotoxic stress responsive RNA helicase, regulates transcriptome dynamics during DNA damage response." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/DDX54_DICDI", "https://meshb.nlm.nih.gov/record/ui?ui=D004249", "http://amigo.geneontology.org/amigo/term/GO:0072423", "http://amigo.geneontology.org/amigo/term/GO:1904507", "http://amigo.geneontology.org/amigo/term/GO:2001020", "http://www.uniprot.org/uniprot/DDX54_HUMAN", "http://www.uniprot.org/uniprot/DDX54_MOUSE", "http://amigo.geneontology.org/amigo/term/GO:0042769", "http://amigo.geneontology.org/amigo/term/GO:1904505", "http://amigo.geneontology.org/amigo/term/GO:0043247", "http://amigo.geneontology.org/amigo/term/GO:1904506", "http://amigo.geneontology.org/amigo/term/GO:0006974", "http://amigo.geneontology.org/amigo/term/GO:0042770" ], "type": "yesno", "id": "5a76056983b0d9ea66000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "DDX54 regulates transcriptome dynamics during DNA damage response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28596291", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 1352, "text": "The contribution of post-transcriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing radiation (IR). Interestingly, more than 260 proteins, including many nucleolar proteins, showed increased binding to poly(A)+RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well-defined class of pre-mRNAs that harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Because DDX54 promotes survival after exposure to IR, its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28596291", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 798, "text": "The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28596291", "endSection": "abstract" } ] }, { "body": "List main clinical features of the POEMS syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10378364", "http://www.ncbi.nlm.nih.gov/pubmed/29157614", "http://www.ncbi.nlm.nih.gov/pubmed/29157615", "http://www.ncbi.nlm.nih.gov/pubmed/29157616", "http://www.ncbi.nlm.nih.gov/pubmed/28856089", "http://www.ncbi.nlm.nih.gov/pubmed/21035860", "http://www.ncbi.nlm.nih.gov/pubmed/2029023", "http://www.ncbi.nlm.nih.gov/pubmed/25984208", "http://www.ncbi.nlm.nih.gov/pubmed/22724593", "http://www.ncbi.nlm.nih.gov/pubmed/10978936", "http://www.ncbi.nlm.nih.gov/pubmed/17895817", "http://www.ncbi.nlm.nih.gov/pubmed/26130736", "http://www.ncbi.nlm.nih.gov/pubmed/7699917", "http://www.ncbi.nlm.nih.gov/pubmed/19863172", "http://www.ncbi.nlm.nih.gov/pubmed/27338259", "http://www.ncbi.nlm.nih.gov/pubmed/24268501", "http://www.ncbi.nlm.nih.gov/pubmed/21221584", "http://www.ncbi.nlm.nih.gov/pubmed/17940990", "http://www.ncbi.nlm.nih.gov/pubmed/25341835", "http://www.ncbi.nlm.nih.gov/pubmed/27208909", "http://www.ncbi.nlm.nih.gov/pubmed/2227242", "http://www.ncbi.nlm.nih.gov/pubmed/8699962", "http://www.ncbi.nlm.nih.gov/pubmed/19546057" ], "ideal_answer": [ "POEMS is an acronym for the main clinical features of the syndrome, namely, Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin abnormalities. Other features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis, and Castleman disease. It is a multisystemc disorder with a good long-term prognosis." ], "exact_answer": [ [ "Polyneuropathy" ], [ "Organomegaly" ], [ "Endocrinopathy" ], [ "M protein" ], [ "Skin abnormalities" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D016878", "http://www.disease-ontology.org/api/metadata/DOID:14039" ], "type": "list", "id": "5a67afb7b750ff445500000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Recognition of a combination of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes, papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis, and Castleman disease is the first step in managing the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Treatment of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome should be directed at the underlying plasma cell clone with risk-adapted therapy based on the extent of the plasma cell disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome is a rare paraneoplastic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157616", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 293, "text": "POEMS is an acronym for the main clinical features of the syndrome, namely, Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27208909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is a multisystem disorder with a good long-term prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27338259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes forms a characteristic multisystem syndrome, Crow-Fukase syndrome, or acronym POEMS syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7699917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a multisystem disorder arising from underlying plasma cell dyscrasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26130736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is an uncommon condition related to a paraneoplastic syndrome secondary to an underlying plasma cell disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25341835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Pulmonary hypertension is one of the well-known clinical manifestations of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, occurring in approximately 25-30% of the affected individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28856089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, a plasma cell dyscrasia associated with pulmonary hypertension, has been treated in the past with anticytokine strategies with a poor outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10978936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "A 48-year-old man with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome had bilateral optic disc edema (ODE), bilateral cystoid macular edema (CME), anasarca, and elevated serum vascular endothelial growth factor (VEGF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17895817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "A 39-year-old woman presented with polyneuropathy, hepatomegaly, splenomegaly, endocrinopathy, monoclonal protein and skin changes, several of the many clinical features of the recently described POEMS syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2227242", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 250, "text": "The acronym POEMS is derived from main features of the syndrome namely 'polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin lesions'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25984208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "POEMS syndrome, also known as Crow-Fukase syndrome, represents a rare multisystem syndrome characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863172", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Polyneuropathy is often an initial manifestation of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome and therefore this disorder is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268501", "endSection": "title" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1192, "text": "POEMS syndrome is a rare paraneoplastic condition, commonly associated with Castleman disease, that manifests with progressive distal polyneuropathy and a monoclonal plasma cell disorder, often accompanied by endocrinopathy, organomegaly, skin changes, sclerotic bone lesions, ascites, erythrocytosis, and thrombocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19546057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "POEMS syndrome, a rare multisystem disease, is a variant of osteosclerotic myeloma and is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2029023", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "We report a case of a 64-year-old man with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome that had been previously misdiagnosed as systemic sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22724593", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "POEMS syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21221584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multisystemic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8699962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 478, "text": "a 39 year old woman presented with polyneuropathy hepatomegaly splenomegaly endocrinopathy monoclonal protein and skin changes several of the many clinical features of the recently described poems syndrome in addition she had a castleman s disease angiofollicular lymph node hyperplasia in this case ascites was a main presenting feature thus the poems syndrome must be added to the list of rare causes of ascites electron microscopy of the liver showed perisinusoidal fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2227242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 825, "text": "the poems syndrome is a rare multisystemic disorder with polyneuropathy organomegaly endocrinopathy of various forms production of monoclonal m component and skin changes we describe a 46 year old man who developed ascites one year after the onset of peripheral neuropathy with accompanying muscle atrophies and increasing weakness extensive evaluation revealed that the patient had no underlying liver disease malignancy infection or cardiac or renal disease the ascites initially responded to high dose corticosteroid therapy the patient had many clinical features of the described poems syndrome including sclerotic bone lesions a persistent lambda paraprotein and refractory ascites in this case ascites was a main presenting feature thus the poems syndrome must be added to the list of rare causes of refractory ascites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10378364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 861, "text": "poems syndrome is a paraneoplastic manifestation associated with hematopoietic disorders such as multiple myeloma and castleman disease poems is an acronym for the main clinical features of the syndrome namely polyneuropathy organomegaly endocrinopathy m protein and skin abnormalities glomeruloid hemangiomas are considered to be a specific clinical marker of poems syndrome however while they are not pathognomonic their presence should raise suspicion of this syndrome or alert clinicians to its possible future development as these lesions can appear years before the onset of the syndrome we report the cases of 2 women with plasma cell dyscrasias and sudden onset of lesions with a vascular appearance and histologic findings consistent with glomeruloid hemangioma recognition of this vascular tumor is important for the early diagnosis of poems syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27208909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1162, "text": "poems syndrome is a rare conglomeration of disorders associated with plasma cell dyscrasia the acronym poems is derived from main features of the syndrome namely polyneuropathy organomegaly endocrinopathy monoclonal gammopathy and skin lesions other clinical features include presence of sclerotic bone lesions castleman s disease papilledema pleural effusion edema ascites erythrocytosis and thrombocytosis myeloma is the most common plasma cell dyscrasia associated with poems syndrome renal involvement is rare and renal biopsy is characterized by glomerular involvement with membranoproliferative glomerulonephritis and endothelial injury we report a case of a 67 year old male who presented with clinical features satisfying the diagnostic criteria of poems syndrome and had rapidly progressive renal failure renal biopsy showed extensive interstitial infiltration by plasma cells and concomitant presence of classic polyarteritis nodosa although association with small vessel vasculitis has been reported in patients with poems syndrome to the best of our knowledge this is the first report of poems syndrome associated with medium sized vessel vasculitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25984208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1074, "text": "poems syndrome also known as crow fukase syndrome represents a rare multisystem syndrome characterized by polyneuropathy organomegaly endocrinopathy m protein and skin changes hypothyroidism is one of the common endocrine abnormalities which are central features of poems syndrome the clinical data associated with the measurement of thyroid function and its clinical significance in poems syndrome is still rare herein we report 24 cases with poems syndrome which were studied thyroid function and clinical manifestations and performed an associated analysis between hypothyroidism and edema effusions of the 24 patients with poems syndrome 17 70 8 had a recognized hypothyroidism including 11 clinical hypothyroidism and 6 subclinical hypothyroidism fourteen patients 58 3 had some form of extravascular volume overload in 14 patients with edema effusions 12 were diagnosed as having hypothyroidism hypothyroidism may be one of causes of edema effusions after thyroid hormone treatment and chemotherapy symptoms of hypothyroidism and edema effusions were improved greatly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1692, "text": "we present a case of a woman with unique multisystem disorder poems syndrome and endocrine abnormalities coexisting with it the poems acronym comprises the dominant features polyneuropathy organomegaly endocrinopathy monoclonal protein m protein skin changes association between plasma cell dyscrasia and polyneuropathy was described in 1956 year by crow the main features were coined in the acronym poems by bardwick in 1980 year the polysymptomatic clinical picture progressive course and no concurrent manifestations of main features impede the diagnosis in this case the first symptoms were the sensomotor polyneuropathy peripheral oedema osteosclerotic bone lesions skin changes organomegaly they preceded diagnosis by 3 years the first endocrinopathy was hypothyroidism definite diagnosis was delayed because we couldn t detect the presence of m protein immunoelectrophoresis didn t detect it but analysis by immunofixation detected m protein in serum and urine within 3 years of the first symptoms she developed hypogonadism hypergonadotropic at first the monotherapy with corticosteroids was used then melfalan with prednisone due to the progression of the disease a thalidomide was used in therapy it is anti vegf agent one of the side effects of the treatment of thalidomide is the progression of polyneuropathy which was observed in this patient after finishing this therapy she received chemotherapy this case report imposes the necessity of constants observation of patients with poems syndrome because there is a possibility of their developing other disorders in the event of coexistence polyneuropathy and plasma cell dyscrasia this disease should be taken into consideration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17940990", "endSection": "abstract" } ] }, { "body": "Which retinal dystrophy related gene is targeted by the AAV2-hRPE65v2 drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28712537" ], "ideal_answer": [ "AAV2-hRPE65v2, also called voretigene neparvovec, targets the RPE65 gene, whose mutations lead to retinal dystrophy." ], "exact_answer": [ "RPE65" ], "type": "factoid", "id": "5a74b1730384be9551000007", "snippets": [ { "offsetInBeginSection": 2506, "offsetInEndSection": 2651, "text": "Voretigene neparvovec gene replacement improved functional vision in RPE65-mediated inherited retinal dystrophy previously medically untreatable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28712537", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 776, "text": "In this open-label, randomised, controlled phase 3 trial done at two sites in the USA, individuals aged 3 years or older with, in each eye, best corrected visual acuity of 20/60 or worse, or visual field less than 20 degrees in any meridian, or both, with confirmed genetic diagnosis of biallelic RPE65 mutations, sufficient viable retina, and ability to perform standardised multi-luminance mobility testing (MLMT) within the luminance range evaluated, were eligible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28712537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28712537", "endSection": "title" } ] }, { "body": "What is the function of yeast TERRA RNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27474163", "http://www.ncbi.nlm.nih.gov/pubmed/19716786", "http://www.ncbi.nlm.nih.gov/pubmed/22139922", "http://www.ncbi.nlm.nih.gov/pubmed/21525956", "http://www.ncbi.nlm.nih.gov/pubmed/22504286", "http://www.ncbi.nlm.nih.gov/pubmed/28815538", "http://www.ncbi.nlm.nih.gov/pubmed/29167439", "http://www.ncbi.nlm.nih.gov/pubmed/22641694" ], "ideal_answer": [ "The ends of linear eukaryotic chromosomes are transcribed into different species of non-coding transcripts (the telomeric transcriptome), including TERRA (telomeric repeat-containing RNA) molecules. TERRA are part of the DNA damage response triggered by dysfunctional telomeres. In addition to its role as a template-encoding telomeric DNA synthesis, telomerase RNA has been shown to function as a flexible scaffold for protein subunits of the RNP holoenzyme.", "We further show that TERRA (Telomeric Repeat-containing RNA) is increased in post-mitotic cells with short telomeres and correlates with telomere rearrangements", "We further show that TERRA (Telomeric Repeat-containing RNA) is increased in post-mitotic cells with short telomeres and correlates with telomere rearrangements Like human and budding yeast, fission yeast harbours a population of telomeric RNA molecules containing G-rich telomeric repeats transcribed from the subtelomere to the telomere. The ends of linear eukaryotic chromosomes are transcribed into different species of non-coding transcripts (the telomeric transcriptome), including TERRA (telomeric repeat-containing RNA) molecules TERRA is part of the DNA damage response triggered by dysfunctional telomeres Telomeric repeat-containing RNA (TERRA) has been implicated in the control of heterochromatin and telomerase. yeast TERRA is regulated by telomere-binding proteins in a chromosome-end-specific manner that is dependent on subtelomeric repetitive DNA elements" ], "type": "summary", "id": "5a8718a261bb38fb24000007", "snippets": [ { "offsetInBeginSection": 667, "offsetInEndSection": 827, "text": "We further show that TERRA (Telomeric Repeat-containing RNA) is increased in post-mitotic cells with short telomeres and correlates with telomere rearrangements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167439", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 484, "text": " Like human and budding yeast, fission yeast harbours a population of telomeric RNA molecules containing G-rich telomeric repeats transcribed from the subtelomere to the telomere.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22139922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The ends of linear eukaryotic chromosomes are transcribed into different species of non-coding transcripts (the telomeric transcriptome), including TERRA (telomeric repeat-containing RNA) molecules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504286", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 881, "text": "TERRA is part of the DNA damage response triggered by dysfunctional telomeres", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Telomeric repeat-containing RNA (TERRA) has been implicated in the control of heterochromatin and telomerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21525956", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 277, "text": "yeast TERRA is regulated by telomere-binding proteins in a chromosome-end-specific manner that is dependent on subtelomeric repetitive DNA elements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21525956", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1424, "text": " Examples of these include the telomerase RNA and telomere-encoded transcripts. In addition to its role as a template-encoding telomeric DNA synthesis, telomerase RNA has been shown to function as a flexible scaffold for protein subunits of the RNP holoenzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28815538", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 631, "text": " Here, we present detailed protocols for live-cell imaging of the Saccharomyces cerevisiae telomerase RNA subunit, called TLC1, and also of the non-coding telomeric repeat-containing RNA TERRA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27474163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Live-cell imaging of budding yeast telomerase RNA and TERRA", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27474163", "endSection": "title" }, { "offsetInBeginSection": 131, "offsetInEndSection": 434, "text": "We show here that TERRA RNA interacts with several telomere-associated proteins, including telomere repeat factors 1 (TRF1) and 2 (TRF2), subunits of the origin recognition complex (ORC), heterochromatin protein 1 (HP1), histone H3 trimethyl K9 (H3 K9me3), and members of the DNA-damage-sensing pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 940, "text": "telomere repeat encoding rna referred to as terra has been identified as a potential component of yeast and mammalian telomeres we show here that terra rna interacts with several telomere associated proteins including telomere repeat factors 1 trf1 and 2 trf2 subunits of the origin recognition complex orc heterochromatin protein 1 hp1 histone h3 trimethyl k9 h3 k9me3 and members of the dna damage sensing pathway sirna depletion of terra caused an increase in telomere dysfunction induced foci aberrations in metaphase telomeres and a loss of histone h3 k9me3 and orc at telomere repeat dna previous studies found that trf2 amino terminal gar domain recruited orc to telomeres we now show that terra rna can interact directly with the trf2 gar and orc1 to form a stable ternary complex we conclude that terra facilitates trf2 interaction with orc and plays a central role in telomere structural maintenance and heterochromatin formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1682, "text": "telomeres play crucial roles in the maintenance of genome integrity and control of cellular senescence most eukaryotic telomeres can be transcribed to generate a telomeric repeat containing rna terra that persists as a heterogeneous nuclear rna and can be developmentally regulated however the precise function and regulation of terra in normal and cancer cell development remains poorly understood here we show that terra accumulates in highly proliferating normal and cancer cells and forms large nuclear foci which are distinct from previously characterized markers of dna damage or replication stress using a mouse model for medulloblastoma driven by chronic sonic hedgehog shh signaling terra rna was detected in tumor but not adjacent normal cells using both rna fluorescence in situ hybridization fish and northern blotting rna fish revealed the formation of terra foci terfs in the nuclear regions of rapidly proliferating tumor cells in the normal developing cerebellum terra aggregates could also be detected in highly proliferating zones of progenitor neurons shh could enhance terra expression in purified granule progenitor cells in vitro suggesting that proliferation signals contribute to terra expression in responsive tissue terra foci did not colocalize with \u03b3h2ax foci promyelocytic leukemia pml or cajal bodies in mouse tumor tissue we also provide evidence that terra is elevated in a variety of human cancers these findings suggest that elevated terra levels reflect a novel early form of telomere regulation during replication stress and cancer cell evolution and the terra rna aggregates may form a novel nuclear body in highly proliferating mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22641694", "endSection": "abstract" } ] }, { "body": "What are the 4 cardinal signs of inflammation according to Celsus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9120866", "http://www.ncbi.nlm.nih.gov/pubmed/23931059", "http://www.ncbi.nlm.nih.gov/pubmed/23583354", "http://www.ncbi.nlm.nih.gov/pubmed/10867774", "http://www.ncbi.nlm.nih.gov/pubmed/12799851", "http://www.ncbi.nlm.nih.gov/pubmed/12776909", "http://www.ncbi.nlm.nih.gov/pubmed/29135930", "http://www.ncbi.nlm.nih.gov/pubmed/7734328", "http://www.ncbi.nlm.nih.gov/pubmed/15041917", "http://www.ncbi.nlm.nih.gov/pubmed/28282278", "http://www.ncbi.nlm.nih.gov/pubmed/28002223" ], "ideal_answer": [ "redness or rubor , heat or calor, swelling or tumor, and pain or dolor", "Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. " ], "exact_answer": [ [ "redness or rubor" ], [ "heat or calor" ], [ "swelling or tumor" ], [ "pain or dolor" ] ], "type": "list", "id": "5a678d63b750ff4455000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28282278", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 392, "text": "Reference was paid to the cardinal signs of inflammation (pain, heat, redness, and swelling)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28002223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Inflammation is the body's response to injury or infection. As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response-redness, heat, swelling and pain; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29135930", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 231, "text": " inflammation gives rise to clinical cardinal signs: rubor, calor, dolor, tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23931059", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 310, "text": "The cardinal signs of inflammation dolor, calor, tumor and rubor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23583354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The concept of the four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, (redness and swelling with heat and pain) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12776909", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 422, "text": "Inflammation is considered a nonspecific response to injury, characterized by exudation of serum into damaged tissue, and identified by the cardinal signs of rubor, calor, dolor, and tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10867774", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1194, "text": "four well-known cardinal signs of Celsus (rubor, calor, tumor, dolor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12799851", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 687, "text": "four cardinal signs of Celsus (redness, heat, swelling and pain). Inflammation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7734328", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1087, "text": "(the famous four cardinal signs of Celsus: pain, redness, swelling, heat) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15041917", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 255, "text": "As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response-redness, heat, swelling and pain; a fifth sign is loss of function.[...", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29135930", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1195, "text": "It was Galen who added the disturbance of function (functio laesa) as the fifth cardinal sign of inflammation to the four well-known cardinal signs of Celsus (rubor, calor, tumor, dolor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12799851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The concept of the four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, (redness and swelling with heat and pain) extended later by functio laesa (loss of function).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12776909", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 440, "text": "The cardinal signs of inflammation dolor, calor, tumor and rubor are intrinsically associated with events including vasodilatation, edema and leukocyte trafficking into the site of inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23583354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28282278", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 589, "text": "The four cardinal signs of inflammation are redness, swelling, heat, and pain, phenomena explained at the cellular level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9120866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "inflammation is the body s response to injury or infection as early as 2000 years ago the roman encyclopaedist aulus cornelius celsus recognised four cardinal signs of this response redness heat swelling and pain a fifth sign is loss of function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29135930", "endSection": "abstract" } ] }, { "body": "Do bacteria from the genus Morexella cause respiratory infections?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8007629", "http://www.ncbi.nlm.nih.gov/pubmed/24786571" ], "ideal_answer": [ "Bacteria from the genus Morexella can cause respiratory infections" ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001419", "https://meshb.nlm.nih.gov/record/ui?ui=D012141", "https://meshb.nlm.nih.gov/record/ui?ui=D012818" ], "type": "yesno", "id": "5a679875b750ff4455000004", "snippets": [ { "offsetInBeginSection": 746, "offsetInEndSection": 918, "text": "gainst pathogens associated with respiratory tract ailments [Staphylococcus aureus (ATCC 25923), Klebsiella pneumoniae (ATCC 13883) and Morexella cattarhalis (ATCC 14468)] ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24786571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 438, "text": "The efficacy and safety of oral ofloxacin, 400 mg once daily, for the treatment of patients with lower respiratory tract infections were studied. The most common species recovered from the sputum specimens of these patients were Haemophilus influenzae, followed by Streptococcus pneumoniae (S. pneumoniae), Staphylococcus aureus (S. aureus), Gram positive cocci unidentified, Pseudomonas aeruginosa (P. aeruginosa), Morexella catarrhalis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8007629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 773, "text": "the efficacy and safety of oral ofloxacin 400 mg once daily for the treatment of patients with lower respiratory tract infections were studied the most common species recovered from the sputum specimens of these patients were haemophilus influenzae followed by streptococcus pneumoniae s pneumoniae staphylococcus aureus s aureus gram positive cocci unidentified pseudomonas aeruginosa p aeruginosa morexella catarrhalis streptococcus epidermidis and another haemophilus species in this order all these bacteria were susceptible to ofloxacin except for one strain of methicillin resistant s aureus a satisfactory clinical outcome was achieved in 34 of 40 patients 85 it is concluded that ofloxacin 400 mg once daily is useful for patients with respiratory tract infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8007629", "endSection": "abstract" } ] }, { "body": "Which two genes are implicated in Juvenile polyposis syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25097590", "http://www.ncbi.nlm.nih.gov/pubmed/26122142", "http://www.ncbi.nlm.nih.gov/pubmed/25389115", "http://www.ncbi.nlm.nih.gov/pubmed/26171675", "http://www.ncbi.nlm.nih.gov/pubmed/17873119", "http://www.ncbi.nlm.nih.gov/pubmed/27375208", "http://www.ncbi.nlm.nih.gov/pubmed/25931195", "http://www.ncbi.nlm.nih.gov/pubmed/25846706", "http://www.ncbi.nlm.nih.gov/pubmed/28428902", "http://www.ncbi.nlm.nih.gov/pubmed/25129392", "http://www.ncbi.nlm.nih.gov/pubmed/21465659", "http://www.ncbi.nlm.nih.gov/pubmed/22810475", "http://www.ncbi.nlm.nih.gov/pubmed/26159157", "http://www.ncbi.nlm.nih.gov/pubmed/22171123" ], "ideal_answer": [ "Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder predisposing to gastrointestinal hamartomatous polyps and cancer with a pathogenic SMAD4 or BMPR1A germline mutation being identified in about 40-50% of patients." ], "exact_answer": [ [ "SMAD4" ], [ "BMPR1A" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050787", "https://meshb.nlm.nih.gov/record/ui?ui=D005796" ], "type": "list", "id": "5a70dbe599e2c3af26000004", "snippets": [ { "offsetInBeginSection": 199, "offsetInEndSection": 379, "text": " JPS is most frequently caused by mutations in the SMAD4 or BMPR1A genes. Herein, we report a child with juvenile polyposis syndrome (JPS) with a novel mutation in the SMAD4 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28428902", "endSection": "abstract" }, { "offsetInBeginSection": 571, "offsetInEndSection": 659, "text": "Subsequent genetic screening revealed a novel mutation in SMAD4, exon 5 (p.Ser144Stop). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28428902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "A SMAD4 mutation indicative of juvenile polyposis syndrome in a family previously diagnosed with Menetrier's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375208", "endSection": "title" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1242, "text": "CONCLUSION: The 1244_1247delACAG mutation of SMAD4 is the cause of JPS and the likely cause of MD in a large family initially diagnosed with MD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375208", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1002, "text": "A dominant 1244_1247delACAG mutation of SMAD4 was identified in each of the subjects with JPS as well as in each of the subjects with MD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375208", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 660, "text": "ince his initial diagnosis of JPS further studies have confirmed an association between JPS and mutations in BMPR1A in chromosome band 10q23.2, which is in close proximity to PTEN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25846706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25931195", "endSection": "title" }, { "offsetInBeginSection": 446, "offsetInEndSection": 531, "text": "Exome sequencing identified a germline heterozygous mutation in SMAD9 (SMAD9(V90M)). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122142", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 340, "text": "Causative mutations for JPS have been identified in two genes to date, SMAD4 and BMPR1A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26159157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Somatic alterations in juvenile polyps from BMPR1A and SMAD4 mutation carriers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26171675", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder predisposing to gastrointestinal hamartomatous polyps and cancer with a pathogenic SMAD4 or BMPR1A germline mutation (1st-hit) being identified in about 40-50% of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26171675", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 411, "text": "The JPS is caused by mutations in SMAD4 and BMPR1A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25097590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Germline mutations in SMAD4 and BMPR1A disrupt the transforming growth factor \u03b2 signal transduction pathway, and are associated with juvenile polyposis syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25389115", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 406, "text": "This study evaluated the differential impact of SMAD4 and BMPR1A gene mutations on cancer risk and oncological phenotype in patients with juvenile polyposis syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25389115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Juvenile polyposis syndrome (JPS) is caused by heterozygous mutations in either SMAD4 or BMPR1A. Individuals with JPS due to mutations in SMAD4 are at greater risk to manifest signs of hereditary hemorrhagic telangiectasia (HHT).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21465659", "endSection": "title" }, { "offsetInBeginSection": 230, "offsetInEndSection": 327, "text": "BMPR1A and SMAD4 germline mutations have been found in patients with juvenile polyposis syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129392", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 883, "text": "In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22171123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Juvenile polyposis syndrome (JPS) is caused by heterozygous mutations in either SMAD4 or BMPR1A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21465659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "BACKGROUND In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17873119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1631, "text": "in patients with juvenile polyposis syndrome jps the frequency of large genomic deletions in the smad4 and bmpr1a genes was unknown mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for jps typical jps and 15 were suspected to have jps by direct sequencing of the two genes point mutations were identified in 30 patients 46 of typical jps using mlpa large genomic deletions were found in 14 of all patients with typical jps six deletions in smad4 and three deletions in bmpr1a mutation analysis of the pten gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients 5 smad4 mutation carriers had a significantly higher frequency of gastric polyposis 73 than did patients with bmpr1a mutations 8 p 0 001 all seven cases of gastric cancer occurred in families with smad4 mutations smad4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without p 0 001 in 22 of the 23 unrelated smad4 mutation carriers hereditary hemorrhagic telangiectasia hht was also diagnosed clinically the documented histologic findings encompassed a wide distribution of different polyp types comparable with that described in hereditary mixed polyposis syndromes hmps screening for large deletions raised the mutation detection rate to 60 in the 65 patients with typical jps a strong genotype phenotype correlation for gastric polyposis gastric cancer and hht was identified which should have implications for counselling and surveillance histopathological results in hamartomatous polyposis syndromes must be critically interpreted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17873119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1758, "text": "juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer the cumulative life time risk of colorectal cancer is 39 and the relative risk is 34 juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes clinically juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis in about 50 60 of patients diagnosed with juvenile polyposis syndrome a germline mutation in the smad4 or bmpr1a gene is found both genes play a role in the bmp tgf beta signalling pathway it has been suggested that cancer in juvenile polyposis may develop through the so called landscaper mechanism where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma recognition of this rare disorder is important for patients and their families with regard to treatment follow up and screening of at risk individuals each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome in addition juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer this review discusses clinical manifestations genetics pathogenesis and management of juvenile polyposis syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22171123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1052, "text": "juvenile polyposis syndrome is an autosomal dominant inherited disorder characterized by multiple juvenile polyps arising in the gastrointestinal tract and an increased risk of gastrointestinal cancers specifically colon cancer bmpr1a and smad4 germline mutations have been found in patients with juvenile polyposis syndrome we identified a bmpr1a mutation which involves a duplication of coding exon 3 c 230 452 333 441dup1995 on multiple ligation dependent probe amplification in a patient with juvenile polyposis syndrome the mutation causes a frameshift producing a truncated protein p d112nfsx2 therefore the mutation is believed to be pathogenic we also identified a duplication breakpoint in which alu sequences are located these results suggest that the duplication event resulted from recombination between alu sequences to our knowledge partial duplication in the bmpr1a gene has not been reported previously this is the first case report to document coding exon 3 duplication in the bmpr1a gene in a patient with juvenile polyposis syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25129392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2283, "text": "juvenile polyposis syndrome is a dominant gi polyposis syndrome defined by 5 gi juvenile polyps or 1 juvenile polyps with a family history of juvenile polyposis mutations in bmpr1a or smad4 are found in 50 of individuals hereditary hemorrhagic telangiectasia is a dominant disorder characterized by epistaxis visceral arteriovenous malformations and telangiectasias hereditary hemorrhagic telangiectasia is diagnosed when 3 criteria including clinical manifestations or a family history are present a juvenile polyposis hereditary hemorrhagic telangiectasia overlap syndrome has previously been reported in 22 of patients with juvenile polyposis due to a smad4 mutation our objective was to determine the prevalence and clinical manifestations of hereditary hemorrhagic telangiectasia by curacao criteria in our juvenile polyposis smad4 patients this was a cohort study of juvenile polyposis patients in our inherited colon cancer registries hereditary hemorrhagic telangiectasia manifestations were obtained from medical records patient contact and or prospective hereditary hemorrhagic telangiectasia screening the curacao criteria was used for diagnosis of hereditary hemorrhagic telangiectasia 3 criteria diagnostic 2 criteria suspect of prevalence and clinical manifestations of hereditary hemorrhagic telangiectasia in juvenile polyposis smad4 patients forty one juvenile polyposis families were identified genetic testing was available for individuals within 18 families smad4 mutations were found in 21 relatives in 9 families eighty one percent of smad4 patients had hereditary hemorrhagic telangiectasia and 14 were suspected of having hereditary hemorrhagic telangiectasia epistaxis and asthma are the most common symptoms in our overlap patients symptomatic and subclinical arteriovenous malformations were noted near universally there was a single tertiary referral center nearly all juvenile polyposis smad4 patients have the overlap syndrome the clinical implications and need for hereditary hemorrhagic telangiectasia screening are important factors for genetic testing in juvenile polyposis health care providers must be cognizant of the juvenile polyposis hereditary hemorrhagic telangiectasia overlap syndrome and the implications for management of these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810475", "endSection": "abstract" } ] }, { "body": "Do chromatin features predict genes associated with eQTLs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23275551" ], "ideal_answer": [ "Yes, genomic proximity plus five TF and chromatin features are able to predict>90% of target genes within 1 megabase of eQTLs" ], "exact_answer": "yes", "type": "yesno", "id": "5a68a463b750ff4455000014", "snippets": [ { "offsetInBeginSection": 530, "offsetInEndSection": 700, "text": "Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict>90% of target genes within 1 megabase of eQTLs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23275551", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 702, "text": "Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict >90% of target genes within 1 megabase of eQTLs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23275551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1330, "text": "Cell type-specific gene expression in humans involves complex interactions between regulatory factors and DNA at enhancers and promoters. Mapping studies for expression quantitative trait loci (eQTLs), transcription factors (TFs) and chromatin markers have become widely used tools for identifying gene regulatory elements, but prediction of target genes remains a major challenge. Here, we integrate genome-wide data on TF-binding sites, chromatin markers and functional annotations to predict genes associated with human eQTLs. Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict >90% of target genes within 1 megabase of eQTLs. Despite being regularly used to map target genes, proximity is not a good indicator of eQTL targets for genes 150 kilobases away, but insulators, TF co-occurrence, open chromatin and functional similarities between TFs and genes are better indicators. Using all six features in the classifier achieved an area under the specificity and sensitivity curve of 0.91, much better compared with at most 0.75 for using any single feature. We hope this study will not only provide validation of eQTL-mapping studies, but also provide insight into the molecular mechanisms explaining how genetic variation can influence gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23275551", "endSection": "abstract" } ] }, { "body": "List the 6 genes associated with the autosomal recessive form of Osteogenesis imperfecta", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18566967", "http://www.ncbi.nlm.nih.gov/pubmed/21567934", "http://www.ncbi.nlm.nih.gov/pubmed/27677223", "http://www.ncbi.nlm.nih.gov/pubmed/21567925", "http://www.ncbi.nlm.nih.gov/pubmed/28116328", "http://www.ncbi.nlm.nih.gov/pubmed/17192541", "http://www.ncbi.nlm.nih.gov/pubmed/23613367", "http://www.ncbi.nlm.nih.gov/pubmed/21670757", "http://www.ncbi.nlm.nih.gov/pubmed/25656619", "http://www.ncbi.nlm.nih.gov/pubmed/19533842", "http://www.ncbi.nlm.nih.gov/pubmed/19907330", "http://www.ncbi.nlm.nih.gov/pubmed/27576954", "http://www.ncbi.nlm.nih.gov/pubmed/25565926", "http://www.ncbi.nlm.nih.gov/pubmed/23301918", "http://www.ncbi.nlm.nih.gov/pubmed/25007323", "http://www.ncbi.nlm.nih.gov/pubmed/23054245", "http://www.ncbi.nlm.nih.gov/pubmed/27942778" ], "ideal_answer": [ "There are at least 6 genes associated with osteogenesis imperfecta, Sp7/Osx, FK506-binding protein, Hsp47/SERPINH1, WNT1, CRTAP, P3H1, and PPIB, LEPRE1,PLOD2, TMEM38B" ], "exact_answer": [ [ "Sp7/Osx" ], [ "FK506-binding protein" ], [ "Hsp47/SERPINH1" ], [ "CRTAP" ], [ "P3H1" ], [ "PPIB" ], [ "WNT1" ], [ "LEPRE1" ], [ "PLOD2" ], [ "TMEM38B" ], [ "BMP1" ], [ "SEC24D" ], [ "cartilage associated protein" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D010013" ], "type": "list", "id": "5a70ce4ab750ff4455000064", "snippets": [ { "offsetInBeginSection": 782, "offsetInEndSection": 1213, "text": "Patients offspring of nonconsanguineous parents were mostly identified withCOL1A1orCOL1A2heterozygous changes, although there were also a few cases withIFITM5andWNT1heterozygous mutations. Only one sporadic patient was a compound heterozygote for two recessive mutations. Patients offspring of consanguineous parents showed homozygous changes in a variety of genes includingCRTAP,FKBP10,LEPRE1,PLOD2,PPIB,SERPINF1,TMEM38B, andWNT1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116328", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1097, "text": "here is minimal literature on the mechanism of action for variants in SERPINH1 resulting in osteogenesis imperfecta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27677223", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 1002, "text": " The majority of patients (about 90%) with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes, which shows an autosomal dominant pattern of inheritance. Six other genes, CRTAP, LEPRE1, FKBP10, PP1B, SP7/Osterix (OSX), and SERPINH1, are associated with autosomal recessive forms of OI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21567925", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1408, "text": "hese results expand the range of CRTAP/LEPRE1 mutations that result in recessive OI ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18566967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25565926", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 309, "text": "We have recently shown that FKBP10 previously reported as a novel autosomal recessive OI gene also defines a novel Bruck syndrome locus (BKS3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21567934", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 359, "text": "Autosomal recessive mutations in a number of genes have also been described, including the BMP1 gene that encodes the mammalian Tolloid (mTLD) and its shorter isoform bone morphogenic protein-1 (BMP1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27576954", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 533, "text": "n this article, we performed clinical assessment and sought mutations in patients from 10 unrelated families with AR-OI, one of whom was presented with the additional features of Bruck syndrome (BS). Pathogenic changes were identified in five different genes: three families had mutations in FKBP10, three in SERPINF1, two in LEPRE1, one in CRTAP, and one in PPIB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613367", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 713, "text": "Two of the genes encoding proteins involved in that enzyme complex, LEPRE1 and cartilage-associated protein, when mutated have been shown to cause autosomal recessive osteogenesis imperfecta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19533842", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 1091, "text": "The discovery of mutations involving CRTAP and LEPRE1 genes in severe/lethal and recessively inherited osteogenesis imperfecta has provided partial answers to questions about 'other' osteogenesis imperfecta genes in patients with an osteogenesis imperfecta phenotype but no COL1A1 and COL1A2 mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19907330", "endSection": "abstract" } ] }, { "body": "What is masitinib an inhibitor of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25961655", "http://www.ncbi.nlm.nih.gov/pubmed/25344204", "http://www.ncbi.nlm.nih.gov/pubmed/24602916" ], "ideal_answer": [ "Masitinib is an inhibitor of mast cell-glia axis and a Fyn kinase blocker. It is an oral tyrosine kinase inhibitor with activity against c-Kit and platelet-derived growth factor receptors (PDGFR)." ], "type": "summary", "id": "5a774585faa1ab7d2e000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "This study evaluated the therapeutic potential of masitinib, an oral tyrosine kinase inhibitor with activity against c-Kit and platelet-derived growth factor receptors (PDGFR), to reduce ischemic brain area and neurological deficit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25344204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Masitinib, a selective tyrosine kinase inhibitor, was investigated as a radiosensitizer in three primary feline injection-site sarcoma (ISS) cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24602916", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 852, "text": "Dual actions of masitinib as an inhibitor of mast cell-glia axis and a Fyn kinase blocker are discussed in the context of AD pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961655", "endSection": "abstract" } ] }, { "body": "What is the name of the RNAi investigational drug being developed against hereditary amyloidosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28893208" ], "ideal_answer": [ "Patisiran.", "The investigational RNAi drug in development for the treatment of hereditary amyloidosis is patisiran." ], "exact_answer": [ "Patisiran" ], "type": "factoid", "id": "5a735b383b9d13c708000002", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 240, "text": "Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28893208", "endSection": "abstract" } ] }, { "body": "What is the function of the H19 (ICR) locus in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19546235", "http://www.ncbi.nlm.nih.gov/pubmed/16815976", "http://www.ncbi.nlm.nih.gov/pubmed/16575185", "http://www.ncbi.nlm.nih.gov/pubmed/24990148", "http://www.ncbi.nlm.nih.gov/pubmed/20047949", "http://www.ncbi.nlm.nih.gov/pubmed/21282187", "http://www.ncbi.nlm.nih.gov/pubmed/19293570", "http://www.ncbi.nlm.nih.gov/pubmed/16378710", "http://www.ncbi.nlm.nih.gov/pubmed/21600199", "http://www.ncbi.nlm.nih.gov/pubmed/24023912", "http://www.ncbi.nlm.nih.gov/pubmed/8842735", "http://www.ncbi.nlm.nih.gov/pubmed/18719115", "http://www.ncbi.nlm.nih.gov/pubmed/16006531", "http://www.ncbi.nlm.nih.gov/pubmed/23585276", "http://www.ncbi.nlm.nih.gov/pubmed/21991322", "http://www.ncbi.nlm.nih.gov/pubmed/19584898", "http://www.ncbi.nlm.nih.gov/pubmed/16107875", "http://www.ncbi.nlm.nih.gov/pubmed/23230275" ], "ideal_answer": [ "We found that localized DNA demethylation at the H19 imprinting control region (ICR) induced by 5-AzaCdR, reduced IGF2, increased H19 expression, increased CTCF and cohesin recruitment and changed histone modifications.", "The H19 locus acts in vivo as a tumor suppressor. The H19 locus belongs to a cluster of imprinted genes that is linked to the human Beckwith-Wiedemann syndrome. The expression of H19 and its closely associated IGF2 gene is frequently deregulated in some human tumors, such as Wilms' tumors." ], "type": "summary", "id": "5a86ecc7faa1ab7d2e000039", "snippets": [ { "offsetInBeginSection": 510, "offsetInEndSection": 729, "text": "We found that localized DNA demethylation at the H19 imprinting control region (ICR) induced by 5-AzaCdR, reduced IGF2, increased H19 expression, increased CTCF and cohesin recruitment and changed histone modifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23585276", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 991, "text": "Furthermore chromatin accessibility was increased locus-wide and chromatin looping topography was altered such that a CTCF site downstream of the H19 enhancers switched its association with the CTCF site upstream of the IGF2 promoters to associate with the ICR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23585276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The parent-of-origin-dependent expression of IGF2 and H19 is controlled by the imprinting center 1 (IC1) consisting of a methylation-sensitive chromatin insulator", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19293570", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1361, "text": "In conclusion, methylation defects at the IGF2-H19 locus can result from inherited mutations of the imprinting center and have high recurrence risk or arise independently from the sequence context and not transmitted to the progeny.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19293570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Specific epigenetic alterations of IGF2-H19 locus in spermatozoa from infertile men.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19584898", "endSection": "title" }, { "offsetInBeginSection": 694, "offsetInEndSection": 881, "text": "In the teratozoospermia group, 11 of 19 patients presented a loss of methylation at variable CpG positions either in the IGF2 DMR2 or in both the IGF2 DMR2 and the 6th CTCF of the H19 DMR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19584898", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1308, "text": " This study demonstrates that epigenetic perturbations of the 6th CTCF site of the H19 DMR might be a relevant biomarker for quantitative defects of spermatogenesis in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19584898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Hyper- and hypomethylation at the IGF2-H19 imprinting control region (ICR) result in reciprocal changes in IGF2-H19 expression and the two contrasting growth disorders, Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282187", "endSection": "abstract" }, { "offsetInBeginSection": 1555, "offsetInEndSection": 1715, "text": "The two alternative chromatin conformations are differently favoured in BWS and SRS likely predisposing the locus to the activation of IGF2 or H19, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21282187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Epigenetic status of the H19 locus in human oocytes following in vitro maturation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16378710", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 626, "text": "To evaluate if maturing human oocytes in vitro would be hazardous at the epigenetic level, we first determined the methylation profile of the H19 differentially methylated region (DMR). The methylation status of the H19 DMR seems particularly vulnerable to in vitro culture conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16378710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "We have identified a region with characteristics of a paternal-specific methylation imprint at the human H19 locus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8842735", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 543, "text": "Structural analysis revealed the presence of CpG islands and a large direct repeat with a 400 bp sequence reiterated several times, but no significant sequence homology to the corresponding region of the mouse H19 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8842735", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 755, "text": "These findings could suggest a role for secondary DNA structure in genomic imprinting across the species, and they also present a puzzling aspect of the evolution of the H19 regulatory region in human and mouse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8842735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Mouse/human sequence divergence in a region with a paternal-specific methylation imprint at the human H19 locus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8842735", "endSection": "title" }, { "offsetInBeginSection": 804, "offsetInEndSection": 947, "text": "Furthermore, the chromatin loop organized by the CTCF-bound, differentially methylated region at the Igf2/H19 locus can be detected in mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16107875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "The H19 locus acts in vivo as a tumor suppressor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18719115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "The H19 locus belongs to a cluster of imprinted genes that is linked to the human Beckwith-Wiedemann syndrome. The expression of H19 and its closely associated IGF2 gene is frequently deregulated in some human tumors, such as Wilms' tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18719115", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 905, "text": "The H19 locus thus clearly displays a tumor suppressor effect in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18719115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Mono-allelic expression at the mouse IGF2/H19 locus is controlled by differential allelic DNA methylation of the imprinting control region (ICR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24023912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "In the mouse Igf2/H19 imprinted locus, differential methylation of the imprinting control region (H19 ICR) is established during spermatogenesis and is maintained in offspring throughout development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23230275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Imprinted expression of the mouse Igf2/H19 locus is controlled by parent-of-origin-specific methylation of the imprinting control region (ICR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20047949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "The imprinted expression of the mouse Igf2/H19 locus is governed by the differential methylation of the imprinting control region (ICR), which is established initially in germ cells and subsequently maintained in somatic cells, depending on its parental origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19546235", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 826, "text": "Microdeletions at the human H19/IGF2 ICR (IC1) are proposed to be responsible for IC1 epimutations associated with imprinting disorders such as Beckwith-Wiedemann syndrome (BWS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990148", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 371, "text": "CTCF binding sites and DNA methylation at the ICR have previously been identified as key cis-acting elements required for proper H19/Igf2 imprinting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21600199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Genomic imprinting at the H19/Igf2 locus is governed by a cis-acting Imprinting-Control Region (ICR), located 2 kb upstream of the H19 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575185", "endSection": "title" }, { "offsetInBeginSection": 305, "offsetInEndSection": 520, "text": "A maternally inherited H19 ICR inhibits Igf2 gene activation by the downstream enhancer due to its insulator function while it suppresses H19 gene transcription by promoter DNA methylation when paternally inherited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006531", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1788, "text": "Thus, the ICR autonomously recapitulated imprinting within the normally nonimprinted transgenic beta-globin gene locus, but the temporal establishment of imprinting methylation differs from that at the endogenous Igf2/H19 locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006531", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 221, "text": "Like most imprinted genes, H19 and Igf2 are regulated by a differentially methylated imprinting control region (ICR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21600199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "It is thought that the H19 imprinting control region (ICR) directs the silencing of the maternally inherited Igf2 allele through a CTCF-dependent chromatin insulator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16815976", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1189, "text": "Mutation of CTCF binding sites in the H19 ICR leads to loss of CTCF binding and de novo methylation of a CTCF target site within Igf2 DMR1, showing that CTCF can coordinate regional epigenetic marks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16815976", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1792, "text": "Thus, the ICR autonomously recapitulated imprinting within the normally nonimprinted transgenic beta-globin gene locus, but the temporal establishment of imprinting methylation differs from that at the endogenous Igf2/H19 locus.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1508, "text": "the imprinted expression of the mouse igf2 h19 locus is governed by the differential methylation of the imprinting control region icr which is established initially in germ cells and subsequently maintained in somatic cells depending on its parental origin by grafting a 2 9 kbp h19 icr fragment into a human beta globin yeast artificial chromosome in transgenic mice we previously showed that the icr could recapitulate imprinted methylation and expression at a heterologous locus suggesting that the h19 icr in the beta globin locus contained sufficient information to maintain the methylation mark k tanimoto m shimotsuma h matsuzaki a omori j bungert j d engel and a fukamizu proc natl acad sci usa 102 10250 10255 2005 curiously however the transgenic h19 icr was not methylated in sperm which was distinct from that seen in the endogenous locus here we reevaluated the ability of the h19 icr to mark the parental origin using more rigid criteria in the testis the methylation levels of the solitary 2 9 kbp transgenic icr fragment varied significantly between six transgenic mouse lines however in somatic cells the paternally inherited icr fragment exhibited consistently higher methylation levels at five out of six randomly integrated sites in the mouse genome these results clearly demonstrated that the h19 icr could acquire parent of origin dependent methylation after fertilization independently of the chromosomal integration site or the prerequisite methylation acquisition in male germ cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19546235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1636, "text": "mono allelic expression at the mouse igf2 h19 locus is controlled by differential allelic dna methylation of the imprinting control region icr because a randomly integrated h19 icr fragment when incorporated into the genome of transgenic mice tgm was allele specifically methylated in somatic but not in germ cells it was suggested that allele discriminating epigenetic signature set within or somewhere outside of the tg h19 icr fragment in germ cells was later translated into a differential dna methylation pattern to test if the chicken \u03b2 globin hs4 chs4 chromatin insulator might interfere with methylation imprinting establishment at the h19 icr we inserted the h19 icr fragment flanked by a set of floxed chs4 core sequences into a human \u03b2 globin locus yac and generated tgm insulated icr tgm as controls the chs4 sequences were removed from one side 5 hs4 deleted icr or both sides pseudo wt icr of the insulated icr by in vivo cre loxp recombination the data show that while maternally inherited transgenic h19 icr was not methylated in insulated icr tgm it was significantly methylated upon paternal transmission though the level was lower than in the pseudo wt icr control because this reduced level of methylation was also observed in the 5 hs4 deleted icr tgm we speculate that the phenotype is due to vezf1 dependent demethylation activity rather than the insulator function borne in chs4 collectively although we cannot rule out the possibility that chs4 is incapable of blocking an allele discriminating signal from outside of the transgene the epigenetic signature appears to be marked intrinsically within the h19 icr.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24023912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1764, "text": "a subset of genes in mammals are subject to genomic imprinting the mouse h19 gene for example is active only when maternally inherited and the neighboring igf2 gene is paternally expressed this imprinted expression pattern is regulated by the imprinting control region icr upstream of the h19 gene a maternally inherited h19 icr inhibits igf2 gene activation by the downstream enhancer due to its insulator function while it suppresses h19 gene transcription by promoter dna methylation when paternally inherited these parent of origin specific functions depend on the allele specific methylation of the icr dna which is established during gametogenesis therefore the icr may also function as a landmark for epigenetic modifications to examine whether the icr confers these activities autonomously we introduced a 2 9 kbp icr containing dna fragment into a human beta globin yeast artificial chromosome at the 3 end of the locus control region and established transgenic mouse lines expression of all of the beta like globin genes was higher when the transgene was paternally inherited in accord with this result transgenic icr dna from nucleated erythrocytes was more heavily methylated when paternally transmitted chromatin immunoprecipitation assays confirmed that ccctc binding factor is preferentially recruited to the maternal transgenic icr in vivo surprisingly however the parent of origin specific methylation pattern was not observed in germ cell dna in testis demonstrating that methylation was established after fertilization thus the icr autonomously recapitulated imprinting within the normally nonimprinted transgenic beta globin gene locus but the temporal establishment of imprinting methylation differs from that at the endogenous igf2 h19 locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16006531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 928, "text": "genomic imprinting at the h19 igf2 locus is governed by a cis acting imprinting control region icr located 2 kb upstream of the h19 gene this region possesses an insulator function which is activated on the unmethylated maternal allele through the binding of the ctcf factor it has been previously reported that paternal transmission of the h19 silk deletion which removes the 3 portion of h19 icr leads to the loss of h19 imprinting here we show that in the liver this reactivation of the paternal h19 gene is concomitant to a dramatic decrease in igf2 mrna levels this deletion alters higher order chromatin architecture igf2 promoter usage and tissue specific expression therefore when methylated the 3 portion of the h19 icr is a bi functional regulatory element involved not only in h19 imprinting but also in formatting the higher order chromatin structure for proper tissue specific expression of both h19 and igf2 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1473, "text": "imprinted expression of the mouse igf2 h19 locus is controlled by parent of origin specific methylation of the imprinting control region icr we previously demonstrated that when placed in a heterologous genomic context the h19 icr fragment contains an intrinsic activity that allows it to acquire differential methylation in somatic cells but not in germ cells in the present study we investigated the requirements for the ctcf binding sites of the icr in the acquisition of post fertilization methylation to this end two mutant icr fragments were introduced into the human beta globin locus in a yeast artificial chromosome transgenic mouse tgm model 4xmut had mutations in all four icr ctcf binding sites that prevented ctcf binding but retained the methylation target cpg motifs and 9cg harbored mutations in the cpg motifs within the ctcf binding sites but each site retained constitutive ctcf binding activity in tgm germ cells and pre implantation blastocysts the absence of ctcf binding sites 4xmut did not lead to hypermethylation of the transgenic h19 icr however after implantation the mutations of ctcf sites 4xmut and 9cg affected the maintenance of methylation these results demonstrated that although the ctcf binding sites are indispensable for maintenance of the unmethylated state of the maternal icr in post implantation embryos they are not required to establish paternal allele specific methylation of the transgenic h19 icr in pre implantation embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20047949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1566, "text": "one of the best studied read outs of epigenetic change is the differential expression of imprinted genes controlled by differential methylation of imprinted control regions icrs to address the impact of genotype on the epigenome we performed a detailed study in 128 pairs of monozygotic mz and 128 pairs of dizygotic dz twins interrogating the dna methylation status of the icrs of igf2 h19 kcnq1 gnas and the non imprinted gene runx1 while we found a similar overall pattern of methylation between mz and dz twins we also observed a high degree of variability in individual cpg methylation levels notably at the h19 igf2 loci a degree of methylation plasticity independent of the genome sequence was observed with both local and regional cpg methylation changes discordant between mz and dz individual pairs however concordant gains or losses of methylation within individual twin pairs were more common in mz than dz twin pairs indicating that de novo and or maintenance methylation is influenced by the underlying dna sequence specifically for the first time we showed that the rs10732516 a polymorphism located in a critical ctcf binding site in the h19 icr locus is strongly associated with increased hypermethylation of specific cpg sites in the maternal h19 allele together our results highlight the impact of the genome on the epigenome and demonstrate that while dna methylation states are tightly maintained between genetically identical and related individuals there remains considerable epigenetic variation that may contribute to disease susceptibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21991322", "endSection": "abstract" } ] }, { "body": "What is the mode of action of teriparatide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26768289", "http://www.ncbi.nlm.nih.gov/pubmed/22403112", "http://www.ncbi.nlm.nih.gov/pubmed/16463613", "http://www.ncbi.nlm.nih.gov/pubmed/20205677", "http://www.ncbi.nlm.nih.gov/pubmed/15940379", "http://www.ncbi.nlm.nih.gov/pubmed/22370296", "http://www.ncbi.nlm.nih.gov/pubmed/20872215", "http://www.ncbi.nlm.nih.gov/pubmed/24625372", "http://www.ncbi.nlm.nih.gov/pubmed/17538470", "http://www.ncbi.nlm.nih.gov/pubmed/26104116", "http://www.ncbi.nlm.nih.gov/pubmed/19604460" ], "ideal_answer": [ "Teripartide is is an effective anabolic (i.e., bone growing) agent used in the treatment of some forms of osteoporosis." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D019379", "http://www.biosemantics.org/jochem#4205694", "http://www.biosemantics.org/jochem#4250366" ], "type": "summary", "id": "5a6f7245b750ff4455000050", "snippets": [ { "offsetInBeginSection": 303, "offsetInEndSection": 767, "text": "Teriparatide results in a rapid increase in bone-formation markers, followed by increases in bone-resorption markers, opening an \"anabolic window,\"a period of time when PTH is maximally anabolic. Teriparatide reverses the structural damage seen in osteoporosis and restores the structure of trabecular bone. It has a positive effect on cortical bone, and any early increases in cortical porosity appear to be offset by increases in cortical thickness and diameter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20872215", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 317, "text": "Teriparatide (recombinant human 1-34 parathyroid hormone) is used to treat women with menopausal osteoporosis and men at high risk for fractures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205677", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 753, "text": ". A new class of drugs called anabolic agents, typified by teriparatide usher, has the potential to reconstitute destroyed bone and bring it to its pristine state. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17538470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Teriparatide [PTH (1-34)] is a genetically engineered analog of human parathyroid hormone that acts as an anabolic drug by increasing activity in both osteoblasts and osteoclasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26768289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Teriparatide (recombinant human parathyroid hormone ) is an anabolic agent approved for the treatment of patients at high risk for fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19604460", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 256, "text": "Teriparatide promotes bone formation, while bisphosphonates suppress bone resorption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26104116", "endSection": "abstract" }, { "offsetInBeginSection": 2373, "offsetInEndSection": 2546, "text": "CONCLUSIONS These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15940379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "teriparatide an anabolic drug for the treatment of patients with osteoporosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16463613", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Teriparatide, a treatment formula of parathyroid hormone (PTH) , is a powerful anabolic agent on bone, improving its mass, geometry and microarchitecture", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22370296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The recombinant amino-terminal fragment of human parathyroid hormone (Teriparatide) is a bone anabolic agent which reduces fracture risk by increasing bone mass and improving bone microarchitecture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22403112", "endSection": "abstract" } ] }, { "body": "What is the Strelka workflow?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "http://www.ncbi.nlm.nih.gov/pubmed/28954988", "http://www.ncbi.nlm.nih.gov/pubmed/29020110", "http://www.ncbi.nlm.nih.gov/pubmed/24678773", "http://www.ncbi.nlm.nih.gov/pubmed/28177460", "http://www.ncbi.nlm.nih.gov/pubmed/23842810", "http://www.ncbi.nlm.nih.gov/pubmed/27002637", "http://www.ncbi.nlm.nih.gov/pubmed/27874022", "http://www.ncbi.nlm.nih.gov/pubmed/22581179" ], "ideal_answer": [ "Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity. Strelka is a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. Strelka has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014644" ], "type": "summary", "id": "5a805974faa1ab7d2e000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581179", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1175, "text": "Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity.RESULTS: We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. We demonstrate that the method has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581179", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 481, "text": "The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity.
RESULTS: We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581179", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1460, "text": "For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27002637", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 464, "text": "RESULTS We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581179", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 662, "text": "Four recently published algorithms for the detection of somatic SNV sites in matched cancer-normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23842810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1247, "text": "whole genome and exome sequencing of matched tumor normal sample pairs is becoming routine in cancer research the consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity we describe strelka a method for somatic snv and small indel detection from sequencing data of matched tumor normal samples the method uses a novel bayesian approach which represents continuous allele frequencies for both tumor and normal samples while leveraging the expected genotype structure of the normal this is achieved by representing the normal sample as a mixture of germline variation with noise and representing the tumor sample as a mixture of the normal sample with somatic variation a natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates we demonstrate that the method has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele frequency tests the strelka workflow source code is available at ftp strelka ftp illumina com csaunders illumina com.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "strelka accurate somatic small variant calling from sequenced tumor normal sample pairs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581179", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1117, "text": "four popular somatic single nucleotide variant snv calling methods varscan somaticsniper strelka and mutect2 were carefully evaluated on the real whole exome sequencing wes depth of 50x and ultra deep targeted sequencing udt seq depth of 370x data the four tools returned poor consensus on candidates only 20 of calls were with multiple hits by the callers for both wes and udt seq mutect2 and strelka obtained the largest proportion of cosmic entries as well as the lowest rate of dbsnp presence and high alternative alleles in control calls demonstrating their superior sensitivity and accuracy combining different callers does increase reliability of candidates but narrows the list down to very limited range of tumor read depth and variant allele frequency calling snv on udt seq data which were of much higher read depth discovered additional true positive variations despite an even more tremendous growth in false positive predictions our findings not only provide valuable benchmark for state of the art snv calling methods but also shed light on the access to more accurate snv identification in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27874022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1358, "text": "high throughput next generation sequencing is a powerful tool to identify the genotypic landscapes of somatic variants and therapeutic targets in various cancers including gastric cancer forming the basis for personalized medicine in the clinical setting although the advent of many computational algorithms leads to higher accuracy in somatic variant calling no standard method exists due to the limitations of each method here we constructed a new pipeline we combined two different somatic variant callers with different algorithms strelka and varscan 2 and evaluated performance using whole exome sequencing data obtained from 19 japanese cases with gastric cancer gc then we characterized these tumors based on identified driver molecular alterations more single nucleotide variants snvs and small insertions deletions were detected by strelka and varscan 2 respectively snvs detected by both tools showed higher accuracy for estimating somatic variants compared with those detected by only one of the two tools and accurately showed the mutation signature and mutations of driver genes reported for gc our combinatorial pipeline may have an advantage in detection of somatic mutations in gc and may be useful for further genomic characterization of japanese patients with gc to improve the efficacy of gc treatments j med invest 64 233 240 august 2017.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1500, "text": "with the advent of relatively affordable high throughput technologies dna sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment somatic cancer only single nucleotide variants snvs are the simplest class of mutation yet their identification in dna sequencing data is confounded by germline polymorphisms tumour heterogeneity and sequencing and analysis errors four recently published algorithms for the detection of somatic snv sites in matched cancer normal sequencing datasets are varscan somaticsniper jointsnvmix and strelka in this analysis we apply these four snv calling algorithms to cancer normal illumina exome sequencing of a chronic myeloid leukaemia cml patient the candidate snv sites returned by each algorithm are filtered to remove likely false positives then characterized and compared to investigate the strengths and weaknesses of each snv calling algorithm comparing the candidate snv sets returned by varscan somaticsniper jointsnvmix2 and strelka revealed substantial differences with respect to the number and character of sites returned the somatic probability scores assigned to the same sites their susceptibility to various sources of noise and their sensitivities to low allelic fraction candidates data accession number sra081939 code at http code google com p snv caller review david adelson adelaide edu au supplementary data are available at bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23842810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1546, "text": "next generation sequencing is extensively applied to catalogue somatic mutations in cancer in research settings and increasingly in clinical settings for molecular diagnostics guiding therapy decisions somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations the advent of many new somatic variant callers creates a need for comparison and validation of the tools as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported we have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers ebcall mutect seurat shimmer indelocator somatic sniper strelka varscan 2 and virmid for the detection of single nucleotide mutations and small deletions and insertions we report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement sequencing depth had markedly diverse impact on individual callers as for some callers increased sequencing depth highly improved sensitivity for snv calling we report ebcall mutect virmid and strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing for indel calling ebcall is superior due to high sensitivity and robustness to changes in sequencing depths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27002637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1290, "text": "high throughput sequencing is rapidly becoming common practice in clinical diagnosis and cancer research many algorithms have been developed for somatic single nucleotide variant snv detection in matched tumor normal dna sequencing although numerous studies have compared the performance of various algorithms on exome data there has not yet been a systematic evaluation using pcr enriched amplicon data with a range of variant allele fractions the recently developed gold standard variant set for the reference individual na12878 by the nist led genome in a bottle consortium nist giab provides a good resource to evaluate admixtures with various snv fractions using the nist giab gold standard we compared the performance of five popular somatic snv calling algorithms gatk unifiedgenotyper followed by simple subtraction mutect strelka somaticsniper and varscan2 for matched tumor normal amplicon and exome sequencing data we demonstrated that the five commonly used somatic snv calling methods are applicable to both targeted amplicon and exome sequencing data however the sensitivities of these methods vary based on the allelic fraction of the mutation in the tumor sample our analysis can assist researchers in choosing a somatic snv calling method suitable for their specific needs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24678773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1393, "text": "identifying genomic variants is a fundamental first step toward the understanding of the role of inherited and acquired variation in disease the accelerating growth in the corpus of sequencing data that underpins such analysis is making the data download bottleneck more evident placing substantial burdens on the research community to keep pace as a result the search for alternative approaches to the traditional download and analyze paradigm on local computing resources has led to a rapidly growing demand for cloud computing solutions for genomics analysis here we introduce the genome variant investigation platform genomevip an open source framework for performing genomics variant discovery and annotation using cloud or local high performance computing infrastructure genomevip orchestrates the analysis of whole genome and exome sequence data using a set of robust and popular task specific tools including varscan gatk pindel breakdancer strelka and genome strip through a web interface genomevip has been used for genomic analysis in large data projects such as the tcga pancanatlas and in other projects such as the icgc pilots cptac icgc tcga dream challenges and the 1000 genomes sv project here we demonstrate genomevip s ability to provide high confidence annotated somatic germline and de novo variants of potential biological significance using publicly available data sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1652, "text": "precision medicine attempts to individualize cancer therapy by matching tumor specific genetic changes with effective targeted therapies a crucial first step in this process is the reliable identification of cancer relevant variants which is considerably complicated by the impurity and heterogeneity of clinical tumor samples we compared the impact of admixture of non cancerous cells and low somatic allele frequencies on the sensitivity and precision of 19 state of the art snv callers we studied both whole exome and targeted gene panel data and up to 13 distinct parameter configurations for each tool we found vast differences among callers based on our comprehensive analyses we recommend joint tumor normal calling with mutect ebcall or strelka for whole exome somatic variant calling and haplotypecaller or freebayes for whole exome germline calling for targeted gene panel data on a single tumor sample lofreqstar performed best we further found that tumor impurity and admixture had a negative impact on precision and in particular sensitivity in whole exome experiments at admixture levels of 60 to 90 sometimes seen in pathological biopsies sensitivity dropped significantly even when variants were originally present in the tumor at 100 allele frequency sensitivity to low frequency snvs improved with targeted panel data but whole exome data allowed more efficient identification of germline variants effective somatic variant calling requires high quality pathological samples with minimal admixture a consciously selected sequencing strategy and the appropriate variant calling tool with settings optimized for the chosen type of data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29020110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1979, "text": "we performed whole exome sequencing of pretreatment biopsies and examined whether genome wide metrics of overall mutational load clonal heterogeneity or alterations at variant gene and pathway levels are associated with treatment response and survival two hundred and three biopsies from the neoaltto trial were analyzed mutations were called with mutect and strelka using pooled normal dna associations between dna alterations and outcome were evaluated by logistic and cox proportional hazards regression there were no recurrent single gene mutations significantly associated with pathologic complete response pcr except pik3ca odds ratio or 0 42 p 0 0185 mutations in 33 of 714 pathways were significantly associated with response but different genes were affected in different individuals pik3ca was present in 23 of these pathways defining a trastuzumab resistance network of 459 genes cases with mutations in this network had low pcr rates to trastuzumab 2 50 4 compared with cases with no mutations 9 16 56 or 0 035 p 0 001 mutations in the regulation of rhoa activity pathway were associated with higher pcr rate to lapatinib or 14 8 adjusted p 0 001 lapatinib trastuzumab or 3 0 adjusted p 0 09 and all arms combined or 3 77 adjusted p 0 02 patients n 124 with mutations in the trastuzumab resistance network but intact rhoa pathway had 2 1 41 pcr rate with trastuzumab alone or 0 026 p 0 001 but adding lapatinib increased pcr rate to 45 17 38 or 1 68 p 0 3 patients n 46 who had no mutations in either gene set had 6 pcr rate 1 15 with lapatinib but had the highest pcr rate 52 8 15 with trastuzumab alone mutations in the rhoa pathway are associated with pcr to lapatinib and mutations in a pik3ca related network are associated with resistance to trastuzumab the combined mutation status of these two pathways could define patients with very low response rate to trastuzumab alone that can be augmented by adding lapatinib or substituting trastuzumab with lapatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28177460", "endSection": "abstract" } ] }, { "body": "Describe the Manta algorithm for detection of structural variants", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26647377" ], "ideal_answer": [ "Manta is a method to discover structural variants and indels from next generation sequencing data. Manta is optimized for rapid germline and somatic analysis, calling structural variants, medium-sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types: for example NA12878 at 50\u00d7 genomic coverage is analyzed in less than 20\u2009min. Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs. Call quality is similar to or better than comparable methods, as determined by pedigree consistency of germline calls and comparison of somatic calls to COSMIC database variants. Manta consistently assembles a higher fraction of its calls to base-pair resolution, allowing for improved downstream annotation and analysis of clinical significance." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000465", "https://meshb.nlm.nih.gov/record/ui?ui=D000073336", "https://meshb.nlm.nih.gov/record/ui?ui=D056914" ], "type": "summary", "id": "5a8053effaa1ab7d2e00001e", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 1187, "text": "We describe Manta, a method to discover structural variants and indels from next generation sequencing data. Manta is optimized for rapid germline and somatic analysis, calling structural variants, medium-sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types: for example NA12878 at 50\u00d7 genomic coverage is analyzed in less than 20\u2009min. Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs. Call quality is similar to or better than comparable methods, as determined by pedigree consistency of germline calls and comparison of somatic calls to COSMIC database variants. Manta consistently assembles a higher fraction of its calls to base-pair resolution, allowing for improved downstream annotation and analysis of clinical significance. We provide Manta as a community resource to facilitate practical and routine structural variant analysis in clinical and research sequencing scenarios.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": ": We describe Manta, a method to discover structural variants and indels from next generation sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1175, "text": "We provide Manta as a community resource to facilitate practical and routine structural variant analysis in clinical and research sequencing scenarios.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 676, "text": "Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 460, "text": "Manta is optimized for rapid germline and somatic analysis, calling structural variants, medium-sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types: for example NA12878 at 50\u00d7 genomic coverage is analyzed in less than 20\u2009min.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1023, "text": "Manta consistently assembles a higher fraction of its calls to base-pair resolution, allowing for improved downstream annotation and analysis of clinical significance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1292, "text": "We provide Manta as a community resource to facilitate practical and routine structural variant analysis in clinical and research sequencing scenarios.
AVAILABILITY AND IMPLEMENTATION: Manta is released under the open-source GPLv3 license.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 479, "text": "Manta is optimized for rapid germline and somatic analysis, calling structural variants, medium-sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types: for example NA12878 at 50\u00d7 genomic coverage is analyzed in less than 20\u2009min.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "UNLABELLED: : We describe Manta, a method to discover structural variants and indels from next generation sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 695, "text": "Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "UNLABELLED: : We describe Manta, a method to discover structural variants and indels from next generation sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "title" }, { "offsetInBeginSection": 473, "offsetInEndSection": 688, "text": "Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "UNLABELLED : We describe Manta, a method to discover structural variants and indels from next generation sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 474, "text": "Manta is optimized for rapid germline and somatic analysis, calling structural variants, medium-sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types: for example NA12878 at 50\u00d7 genomic coverage is analyzed in less than 20\u2009min.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 690, "text": "Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1189, "text": "We provide Manta as a community resource to facilitate practical and routine structural variant analysis in clinical and research sequencing scenarios.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1037, "text": "Manta consistently assembles a higher fraction of its calls to base-pair resolution, allowing for improved downstream annotation and analysis of clinical significance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1391, "text": "we describe manta a method to discover structural variants and indels from next generation sequencing data manta is optimized for rapid germline and somatic analysis calling structural variants medium sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types for example na12878 at 50 genomic coverage is analyzed in less than 20 min manta can discover and score variants based on supporting paired and split read evidence with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor normal sample pairs call quality is similar to or better than comparable methods as determined by pedigree consistency of germline calls and comparison of somatic calls to cosmic database variants manta consistently assembles a higher fraction of its calls to base pair resolution allowing for improved downstream annotation and analysis of clinical significance we provide manta as a community resource to facilitate practical and routine structural variant analysis in clinical and research sequencing scenarios manta is released under the open source gplv3 license source code documentation and linux binaries are available from https github com illumina manta csaunders illumina com supplementary data are available at bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "manta rapid detection of structural variants and indels for germline and cancer sequencing applications", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647377", "endSection": "title" } ] }, { "body": "Is Kummell\u2019s disease an avascular necrosis of the vertebral body?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22220246", "http://www.ncbi.nlm.nih.gov/pubmed/19534241", "http://www.ncbi.nlm.nih.gov/pubmed/23814399", "http://www.ncbi.nlm.nih.gov/pubmed/19124637", "http://www.ncbi.nlm.nih.gov/pubmed/28913640", "http://www.ncbi.nlm.nih.gov/pubmed/19321060", "http://www.ncbi.nlm.nih.gov/pubmed/21811863", "http://www.ncbi.nlm.nih.gov/pubmed/11915453", "http://www.ncbi.nlm.nih.gov/pubmed/19949820", "http://www.ncbi.nlm.nih.gov/pubmed/28160398" ], "ideal_answer": [ "Yes, Kummell\u2019s disease is an avascular necrosis of the vertebral body." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D010020", "http://www.disease-ontology.org/api/metadata/DOID:6603" ], "type": "yesno", "id": "5a787544faa1ab7d2e00000b", "snippets": [ { "offsetInBeginSection": 13, "offsetInEndSection": 326, "text": " Kummell's disease is an avascular necrosis of the vertebral body, secondary to a vertebral compression fracture. This entity is characterised by the gradual development in time of a vertebral body collapse following a trivial spinal trauma, involving a worsening back pain associated with a progressive kyphosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28913640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Kummell's disease is a rare spinal disorder characterized as avascular necrosis of a vertebral body occurring in a delayed fashion after minor trauma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11915453", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Kummell's disease is a spinal disorder characterized by delayed post-traumatic collapse of a vertebral body with avascular necrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22220246", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Kummell disease, or avascular necrosis of a vertebral body, presents as vertebral osteonecrosis typically affecting a thoracic vertebra with compression deformity, intravertebral vacuum cleft, and exaggerated kyphosis weeks to months after a minor traumatic injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23814399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "INTRODUCTION Kummell's disease is an avascular necrosis of the vertebral body, secondary to a vertebral compression fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28913640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Kummel disease is the eponym for avascular necrosis of the vertebral body after a vertebral compression fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19124637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "kummell s disease delayed post traumatic osteonecrosis of the vertebral body", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19949820", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Kummell's disease, caused by osteonecrosis of the vertebral body, is a cause of vertebral collapse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28160398", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 152, "text": "Kummell's disease is a post-traumatic vertebral body collapse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19534241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Kummell's disease is a rare, delayed posttraumatic collapse of a vertebral body that can occur several months or even years after an osteoporotic compression fracture. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21811863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Avascular necrosis of a vertebral body, a relatively uncommon entity, is caused by malignancy, infection, radiation, systemic steroid treatment, trauma, and the like.1 Vertebral osteonecrosis induced by trauma is called Kvmell's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19321060", "endSection": "abstract" } ] }, { "body": "What causes \"Puffy hand syndrome\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15529083", "http://www.ncbi.nlm.nih.gov/pubmed/11195858", "http://www.ncbi.nlm.nih.gov/pubmed/18299911", "http://www.ncbi.nlm.nih.gov/pubmed/23856549", "http://www.ncbi.nlm.nih.gov/pubmed/19216010", "http://www.ncbi.nlm.nih.gov/pubmed/17072191", "http://www.ncbi.nlm.nih.gov/pubmed/27269656", "http://www.ncbi.nlm.nih.gov/pubmed/16911735", "http://www.ncbi.nlm.nih.gov/pubmed/24198977" ], "ideal_answer": [ "Puffy hand syndrome is a complication of intravenous drug abuse." ], "exact_answer": [ "intravenous drug abuse" ], "type": "factoid", "id": "5a7346662dc08e987e00001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Intravenous drug addiction is responsible for many complications, especially cutaneous and infectious. There is a syndrome, rarely observed in rheumatology, resulting in \"puffy hands\": the puffy hand syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269656", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 705, "text": "They presented with an edema of the hands, bilateral, painless, no pitting, occurring in one of our patient during heroin intoxication, and in the other 2 years after stopping injections. In our two patients, additional investigations (biological, radiological, ultrasound) were unremarkable, which helped us, in the context, to put the diagnosis of puffy hand syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Puffy hand syndrome develops after long-term intravenous drug addiction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The authors report an original clinical presentation of factitious disorders of the upper extremity in an ex-drug-addict patient with puffy hand syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23856549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Puffy hand syndrome is an unrecognized complication of intravenous drug abuse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19216010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Puffy hand syndrome due to drug addiction: a case-control study of the pathogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911735", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "AIM: We studied the pathogenesis of puffy hand syndrome of intravenous drug use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911735", "endSection": "abstract" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1366, "text": "CONCLUSIONS: Injection practices are likely to cause puffy hands syndrome, but buprenorphine misuse should not be considered as a significant risk factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "[Puffy hand syndrome in drug addiction treated by low-stretch bandages].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17072191", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "BACKGROUND: Puffy hand syndrome is a complication of intravenous drug abuse, which has no current available treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17072191", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 508, "text": "Physiopathological mechanisms of the puffy hand syndrome are unclear and include venous and lymphatic insufficiencies, infectious complications and direct toxicity of injected drugs and their adulterants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19216010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Puffy hand syndrome is a complication of intravenous drug abuse, which has no current available treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17072191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Puffy hand syndrome is an unrecognized complication of intravenous drug abuse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19216010", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 245, "text": "The puffy hand sign is a more uncommon complication of hard-core injection addicts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529083", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 798, "text": "Other IVDA complications in the upper extremity affecting blood vessels and lymphatics include hematoma, arterial aneurysm and pseudoaneurysm, thrombosis, thrombophlebitis, \"puffy hand\" syndrome, and lymphadenopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18299911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "AIM: We studied the pathogenesis of puffy hand syndrome of intravenous drug use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911735", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1406, "text": "In 69.7% of the cases and 59.4% of the controls, respectively, there was a high-dose sublingual buprenorphine misuse, although it appeared not to be a significant risk factor for puffy hand syndrome.
CONCLUSIONS: Injection practices are likely to cause puffy hands syndrome, but buprenorphine misuse should not be considered as a significant risk factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 625, "text": "puffy hand syndrome is an unrecognized complication of intravenous drug abuse this painless syndrome appears during or after a long period of drug addiction it involves the hands and sometimes the forearms and may cause functional aesthetic and social disturbances when the hand volume is important physiopathological mechanisms of the puffy hand syndrome are unclear and include venous and lymphatic insufficiencies infectious complications and direct toxicity of injected drugs and their adulterants low stretch bandage and elastic garment usually used in lymphedema treatment are proposed to treat the puffy hand syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19216010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1376, "text": "we studied the pathogenesis of puffy hand syndrome of intravenous drug use we hypothesized that injections of high dose sublingual buprenorphine instead of the recommended sublingual administration could play an important role in lymphatic obstruction and destruction we set up a case control study in substitution centres recruiting intravenous drug addicts with and without puffy hands respectively the subjects were asked to answer anonymously a questionnaire of 40 items comprising social and demographic status history of illicit drugs use buprenorphine misuse and injection practices we included 33 cases and 33 controls mean age of 34 years they were past heroin users mainly methadone substituted in multivariate analysis sex women or 8 9 p 0 03 injections in the hands or 5 9 p 0 03 injections in the feet or 6 5 p 0 01 and the absence of tourniquet or 7 0 p 0 02 were significant risk factors for puffy hand syndrome in 69 7 of the cases and 59 4 of the controls respectively there was a high dose sublingual buprenorphine misuse although it appeared not to be a significant risk factor for puffy hand syndrome injection practices are likely to cause puffy hands syndrome but buprenorphine misuse should not be considered as a significant risk factor however intravenous drug users must still be warned of local and systemic complications of intravenous drug misuse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16911735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "puffy hand in long term intravenous drug users", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529083", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1540, "text": "narcotic addiction may induce systemic and local complications intravenous injections of drugs can cause venous thrombosis and septic or embolic complications the puffy hand sign is a more uncommon complication of hard core injection addicts three long term intravenous drug users two males one female mean age 30 6 years 26 37 presented puffy hands these patients had been drug addicts for four to twelve years mean duration 7 3 years and had stopped heroin injections for 3 5 years mean 4 6 participating in a buprenorphine substitution program the edema appeared several years after drug cessation 1 5 5 mean 2 3 typically the puffiness was bilateral the hands swollen from the proximal segments of the fingers to the wrist in one patient the edema was localized both in the hands and in the feet the edema was not pitting and unaffected by elevation duplex ultrasound examination of the extremities was normal lymphangiography performed in one patient was consistent with deep lymphatic destruction puffy hand syndrome appears to be the end result of lymphatic obstruction repeated injections of drugs in or outside the veins destroy the lymphatics buprenorphine may play an important role in the puffy hand sign although it is supposed to be administered orally many drug addicts use it as an i v solution because buprenorphine is poorly soluble it causes lymphatic obstruction this type of hand for which no therapy exists must be differentiated from deep palmar space infection with dorsal edema which requires incision and drainage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1353, "text": "puffy hand syndrome is a complication of intravenous drug abuse which has no current available treatment arm and forearm edema are voluminous and cause functional and aesthetic disturbances we report two cases successfully treated by low stretch bandages a 40 year old man and a 34 year old woman both intravenous drug users with puffy hand syndrome were hospitalized for 11 days treatment included daily multilayer bandaging lymphedema volumes calculated by utilizing the formula for a truncated cone decreased by 16 on the left side and 12 on the right side for the first patient and 31 and 17 for the second hand circumference decreased 4 3 cm on the left side and 3 2 cm on the right side in case 1 and 2 5 cm and 1 9 cm respectively for case 2 the patients were taught self bandaging techniques during their hospital stays elastic gloves were fitted at the end of treatment reduction of lymphedema volume remained stable after 18 months in one patient while for the second patient further treatment and hospitalization were required due to poor compliance the pathogenesis of this edema is probably multifactorial venous lymphatic insufficiency and the direct toxicity of injected drugs lymphedema treatment currently consists of low stretch bandaging and wearing elastic garments which is effective in decreasing the volume of puffy hand syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17072191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1736, "text": "the incidence of vascular complications due to drug abuse is at present increasing due to new types of drugs and to the different ways of intake of such substances the vascular complications related to drug abuse may affect venous arterious and lymphatic districts and in particular ischemia following intra arterial injections arterious and venous pseudoaneurysm vasculitis aneurysms aortic dissections abscesses complicated by erosions of vessels arteriovenous fistulas compartment syndrome superficial and deep venous thrombosis septic trombophlebitis puffy hand syndrome the scientific knowledge in this matter is incomplete because of the new pathological cases and the lack of information regarding the efficacy of different treatments the authors report four patients affected by vascular pathologies due to drug abuse in one case a heroin addict has undergone multiple fasciotomies for compartimental syndrome arising because the patient maintained an innatural posture for several hours during an overdose coma in a second case a segmental right subclavear deep venous thrombosis has been treated by pharmacological therapy with satisfactory functional recovery of the arm a third patient has been successfully submitted to intra arterial pharmacological vasodilatation for generalised lower limbs vasospasm caused by drug abuse in the last case the voluntary swallowing of a great dose of cocaine caused the patient s death after multiple ischemic and hemorrhagic cerebral episodes after the description of these cases a review of the recent literature and some observations on this topic are presented a better knowledge of vascular complications due to drug abuse should improve the therapeutical approach of these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11195858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 907, "text": "intravenous drug addiction is responsible for many complications especially cutaneous and infectious there is a syndrome rarely observed in rheumatology resulting in puffy hands the puffy hand syndrome we report two cases of this condition from our rheumatologic consultation our two patients had intravenous drug addiction they presented with an edema of the hands bilateral painless no pitting occurring in one of our patient during heroin intoxication and in the other 2 years after stopping injections in our two patients additional investigations biological radiological ultrasound were unremarkable which helped us in the context to put the diagnosis of puffy hand syndrome the pathophysiology still unclear is based in part on a lymphatic toxicity of drugs and their excipients there is no etiological treatment but elastic compression by night has improved edema of the hands in one of our patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1149, "text": "puffy hand syndrome develops after long term intravenous drug addiction it is characterized by a nonpitting edema affecting the dorsal side of fingers and hands with puffy aspect frequency and severity of the complications of this syndrome are rarely reported local infectious complications such as cellulitis can be severe and can enable the diagnosis herein we report the case of a 41 year old man who went to the emergency department for abdominal pain fever and bullous lesions of legs and arms with edema bacteriologic examination of a closed bullous lesion evidenced a methicillin sensitive staphylococcus aureus the abdomen computed tomography excluded deep infections and peritoneal effusion the patient was successfully treated by intravenous oxacillin and clindamycin he had a previous history of intravenous heroin addiction we retained the diagnosis of puffy hand syndrome revealed by a severe staphylococcal infection with toxic involvement mimicking a four limbs cellulitis puffy hand syndrome apart from the chronic lymphedema treatment has no specific medication available prophylactic measures against skin infections are essential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24198977", "endSection": "abstract" } ] }, { "body": "Describe mechanism of action of Ozanimod.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28398597", "http://www.ncbi.nlm.nih.gov/pubmed/26990079", "http://www.ncbi.nlm.nih.gov/pubmed/28147349", "http://www.ncbi.nlm.nih.gov/pubmed/27144850", "http://www.ncbi.nlm.nih.gov/pubmed/28812220", "http://www.ncbi.nlm.nih.gov/pubmed/26702336", "http://www.ncbi.nlm.nih.gov/pubmed/28765121", "http://www.ncbi.nlm.nih.gov/pubmed/28279838", "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "http://www.ncbi.nlm.nih.gov/pubmed/26239599", "http://www.ncbi.nlm.nih.gov/pubmed/26398681", "http://www.ncbi.nlm.nih.gov/pubmed/27049060" ], "ideal_answer": [ "Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in clinical development for the treatment of chronic immune-mediated, inflammatory diseases, such as multiple sclerosis and inflammatory bowel disease. Yet its exact mechanism of action is unknown." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D045504" ], "type": "summary", "id": "5a7247182dc08e987e000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049060", "endSection": "abstract" }, { "offsetInBeginSection": 1638, "offsetInEndSection": 1735, "text": "Finally, the S1P1 receptor agonist ozanimod showed promise in early trials in ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28147349", "endSection": "abstract" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1484, "text": "ntil recently, three S1P modulators with differing selectivity for S1P receptors were in clinical development for IBD: ozanimod (RPC1063), etrasimod (APD334) and amiselimod (MT-1303).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28279838", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 397, "text": "Ozanimod is an oral selective modulator of S1P1Rand S1P5Rreceptors in clinical development for the treatment of chronic immune-mediated, inflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28398597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1254, "text": "Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28765121", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 637, "text": "RECENT FINDINGS: We discuss the most important findings of one published phase II trial that targeted the \u03b27 integrin (etrolizumab), two phase II trials that targeted the \u03b14\u03b27 integrin ligand: mucosal addressin cell adhesion molecule 1 (MAdCAM-1, PF-00547659), a phase II trial targeting the chemokine IP-10 (CXCL10) in Crohn's, and a phase II trial that targeted the sphingosine-1-phosphate receptor-1: ozanimod in patients with ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26398681", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 978, "text": " As such, agents that more selectively target subtype 1 of the S1PR are of interest and are at various stages of development. These include ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28812220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Ozanimod (RPC1063) is an oral selective modulator of the sphingosine-1-phosphate 1 and 5 receptors under development for the treatment of relapsing multiple sclerosis and inflammatory bowel disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Ozanimod (RPC1063) is an oral selective modulator of the sphingosine-1-phosphate 1 and 5 receptors under development for the treatment of relapsing multiple sclerosis and inflammatory bowel disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "BACKGROUND: Ozanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract.
METHODS: We conducted a double-blind, placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1194, "text": "several new medications are being investigated in late phase studies for the treatment of patients with relapsing or progressive multiple sclerosis ms these agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities the majority of investigational trials involve selective sphingosine 1 phosphate receptor 1 immunomodulators such as laquinimod ozanimod ponesimod and siponimod in an effort to build on the success of fingolimod ocrelizumab is a cd20 positive b cell targeting monoclonal antibody with a promising new mechanism of action ofatumumab is also a cd20 inhibitor daclizumab an interleukin 2 inhibitor has evidence of good efficacy but is associated with unfavorable side effects masitinib is a mast cell inhibitor that also has shown efficacy in alzheimer s disease and amyotrophic lateral sclerosis phase 3 trials for some of these agents will conclude in the next 12 months and their manufacturers are expected to apply for us food and drug administration approval soon thereafter this review article summarizes data for newly approved and late phase investigational agents for the treatment of patients with ms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26702336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1009, "text": "sphingosine 1 phosphate s1p receptor modulators possess a unique mechanism of action as disease modifying therapy for multiple sclerosis ms subtype 1 s1p receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes the s1p receptor modulators indirectly antagonize the receptor s function and sequester lymphocytes in lymph nodes fingolimod was the first s1p agent approved in the usa in 2010 for relapsing ms after two phase iii trials freedoms and transforms demonstrated potent efficacy and good safety and tolerability post marketing experience as well as a third phase iii trial freedoms ii also showed favorable results more selective s1p receptor agents ponesimod act128800 siponimod baf312 ozanimod rpc1063 ceralifimod ono 4641 gsk2018682 and mt 1303 are still in relatively early stages of development but phase i and ii trials showed promising efficacy and safety however these observations have yet to be reproduced in phase iii clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26239599", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "results from the first in human study with ozanimod a novel selective sphingosine 1 phosphate receptor modulator", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28398597", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "cardiac safety of ozanimod a novel sphingosine 1 phosphate receptor modulator results of a thorough qt qtc study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "effects of high and low fat meals on the pharmacokinetics of ozanimod a novel sphingosine 1 phosphate receptor modulator", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "ozanimod rpc1063 is a potent sphingosine 1 phosphate receptor 1 s1p1 and receptor 5 s1p5 agonist with autoimmune disease modifying activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26990079", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1220, "text": "sphingosine 1 phosphate receptor s1pr modulators possess a unique mechanism of action in the treatment of multiple sclerosis ms subtype 1 of the s1pr is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes the s1pr modulators indirectly antagonize the receptor s function leading to sequestration of lymphocytes in the lymph nodes fingolimod was the first s1pr modulator to receive regulatory approval for relapsing remitting ms after 2 phase iii trials demonstrated potent efficacy safety and tolerability fingolimod can cause undesirable effects as a result of its interaction with other s1pr subtypes which are expressed in diverse tissues including cardiac myocytes as such agents that more selectively target subtype 1 of the s1pr are of interest and are at various stages of development these include ponesimod act128800 siponimod baf312 ozanimod rpc1063 ceralifimod ono 4641 gsk2018682 and mt 1303 data from phase ii trials and early results from phase iii studies have been promising and will be presented in this review of special interest are results from the expand study of siponimod which suggest a potential role for s1pr modulators in secondary progressive ms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28812220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1346, "text": "the sphingosine 1 phosphate receptor 1 s1p agonist ozanimod ameliorates ulcerative colitis yet its mechanism of action is unknown here we examine the cell subsets that express s1p in intestine using s1p egfp mice the regulation of s1p expression in lymphocytes after administration of dextran sulfate sodium dss after colitis induced by transfer of cd4 cd45rb cells and by crossing a mouse with tnf driven ileitis with s1p egfp mice we then assayed the expression of enzymes that regulate intestinal s1p levels and the effect of fty720 on lymphocyte behavior and s1p expression we found that not only t and b cells express s1p but also dendritic dc and endothelial cells furthermore chronic but not acute inflammatory signals increased s1p expression while the enzymes that control tissue s1p levels in mice and humans with inflammatory bowel disease ibd were uniformly dysregulated favoring synthesis over degradation finally we observed that fty720 reduced t cell velocity and induced s1p degradation and retention of na\u00efve but not effector t cells our data demonstrate that chronic inflammation modulates s1p expression and tissue s1p levels and suggests that the anti inflammatory properties of s1pr agonists might not be solely due to their lymphopenic effects but also due to potential effects on dc migration and vascular barrier function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1246, "text": "ozanimod rpc1063 is an oral selective modulator of the sphingosine 1 phosphate 1 and 5 receptors under development for the treatment of relapsing multiple sclerosis and inflammatory bowel disease the effects of high fat and low fat meals on the pharmacokinetics pk of a single oral dose of ozanimod were evaluated in 24 healthy volunteers in a randomized open label crossover trial each subject received a 1 mg dose of ozanimod hydrochloride under 3 meal conditions fasted high fat and low fat each separated by 7 days mean plasma concentration time profiles for ozanimod and its active metabolites rp101988 major rp101075 minor were similar under all 3 conditions moreover all pk parameters for ozanimod rp101988 and rp101075 were similar under the 3 meal conditions the 90 confidence intervals cis for the ratios of geometric least squares mean fed fasted were within the equivalence limits of 0 80 to 1 25 for area under the concentration time curve from time 0 to infinity auc and maximum plasma concentration c for ozanimod rp101988 and rp101075 except for the high fat effect on rp101075 c 90 ci 0 76 0 88 given this lack of a food effect on the exposure of ozanimod and its active metabolites ozanimod can be taken without regard to meals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1365, "text": "ozanimod is a novel selective oral sphingosine 1 phosphate 1 and 5 receptor modulator in development for multiple sclerosis and inflammatory bowel disease this randomized double blind placebo controlled positive controlled parallel group thorough qt study characterized the effects of ozanimod on cardiac repolarization in healthy subjects eligible subjects were randomized to 1 of 2 groups ozanimod escalated from 0 25 to 2 mg over 14 days or placebo for 14 days a single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17 the primary end point was the time matched placebo corrected baseline adjusted mean qtcf \u03b4\u03b4qtcf a total of 113 124 91 1 subjects completed the study the upper limits of the 2 sided 90 confidence intervals for \u03b4\u03b4qtcf for both ozanimod 1 and 2 mg were below the 10 millisecond regulatory threshold no qtcf 480 milliseconds or postdose change in qtcf of 60 milliseconds was observed there was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and \u03b4\u03b4qtcf although ozanimod blunted the observed diurnal increase in heart rate excursions below predose heart rates were no greater than with placebo results demonstrate that ozanimod does not prolong the qtc interval or cause clinically significant bradycardia supporting ozanimod s evolving favorable cardiac safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "abstract" } ] }, { "body": "Describe swirl sign in intracerebral hemorrhage.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28894943", "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "http://www.ncbi.nlm.nih.gov/pubmed/28701501", "http://www.ncbi.nlm.nih.gov/pubmed/24474263", "http://www.ncbi.nlm.nih.gov/pubmed/23517301", "http://www.ncbi.nlm.nih.gov/pubmed/18065505" ], "ideal_answer": [ "Swirl sign is described as areas of low attenuation, radiolucency or irregular density. It was previously described in epidural hematomas. In intracerebral hemorrhage swirl sign is associated with greater hematoma volume, unfavorable outcomes and greater mortality risk." ], "type": "summary", "id": "5a7242a22dc08e987e00000e", "snippets": [ { "offsetInBeginSection": 1231, "offsetInEndSection": 1491, "text": "Univariate analysis showed that the presence of extravasation on CT, large initial hematoma size (>30 mL), the presence of \"swirl sign\" on NCCT, the Glasgow Coma Scale and ICH scores, and international normalized ratio were associated with increased mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18065505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: Swirl sign has previously been described in epidural hematomas as areas of low attenuation, radiolucency or irregular density. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1500, "text": " 61% of patients with swirl sign were dead at one month compared with 21% of those with no swirl sign (p<0.001). Only 19% of patients with swirl sign exhibited favorable outcome at three months compared with 53% of those with no swirl sign (p<0.001). Patients with swirl sign exhibited larger ICHs with average ICH-volume 52 \u00b1 50 ml (median 42 ml) compared with 15 \u00b1 25 ml (median 6) in patients whose CT did not show swirl sign (p<0.001). Swirl sign was independent predictor of death at one month (p = 0.03; adjusted odds ratio 2.6, 95% CI 1.1 - 6), and functional outcome at three months (p = 0.045; adjusted odds ratio 2.6, 95% CI 1.02 - 6.5).CONCLUSIONS: As swirl sign showed to be an ominous sign, we recommend identification of this sign in cases of ICHs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 720, "text": "The following NCCT markers were identified: intrahematoma hypodensities, black hole sign, swirl sign, blend sign, heterogeneous hematoma density, and irregular shape. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28701501", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1159, "text": "Risk of evolution toward BD was classified as low (corneal reflexes present and no swirl sign), high (\u22651 corneal reflexes abolished and swirl sign), and intermediate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517301", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1212, "text": "Patients with swirl sign exhibited larger ICHs with average ICH-volume 52 \u00b1 50 ml (median 42 ml) compared with 15 \u00b1 25 ml (median 6) in patients whose CT did not show swirl sign (p < 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "BACKGROUND: Swirl sign has previously been described in epidural hematomas as areas of low attenuation, radiolucency or irregular density.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1550, "text": "Swirl sign was independent predictor of death at one month (p = 0.03; adjusted odds ratio 2.6, 95% CI 1.1 - 6), and functional outcome at three months (p = 0.045; adjusted odds ratio 2.6, 95% CI 1.02 - 6.5).
CONCLUSIONS: As swirl sign showed to be an ominous sign, we recommend identification of this sign in cases of ICHs.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "BACKGROUND: Swirl sign has previously been described in epidural hematomas as areas of low attenuation, radiolucency or irregular density.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "title" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1814, "text": "CONCLUSIONS Detection of hematocrit effect by CT scanning of intracranial hematomas should be cautionary in oral anticoagulant use, while detection of swirl sign should be suggestive of active hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24474263", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1515, "text": "CONCLUSIONS As swirl sign showed to be an ominous sign, we recommend identification of this sign in cases of ICHs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 1630, "offsetInEndSection": 1779, "text": "In conclusion, the occurrence of the swirl sign on the head CT scan of patients with AEDH was found to be significantly associated with poor outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28894943", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1190, "text": "Patients with swirl sign exhibited larger ICHs with average ICH-volume 52 \u00b1 50 ml (median 42 ml) compared with 15 \u00b1 25 ml (median 6) in patients whose CT did not show swirl sign (p < 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1399, "text": "swirl sign has previously been described in epidural hematomas as areas of low attenuation radiolucency or irregular density the aims of this study were to describe swirl sign in ich study its prevalence study the reliability of the subjective evaluation on computed tomography ct and to explore its prognostic value cts of 203 patients with ich were retrospectively evaluated for the presence of swirl sign association between swirl sign and different clinical and radiological variables was studied inter and intraobserver agreement with regard to the occurrence of swirl sign was substantial \u043a 0 80 and almost perfect \u043a 0 87 respectively swirl sign was found in 30 of the study population 61 of patients with swirl sign were dead at one month compared with 21 of those with no swirl sign p 0 001 only 19 of patients with swirl sign exhibited favorable outcome at three months compared with 53 of those with no swirl sign p 0 001 patients with swirl sign exhibited larger ichs with average ich volume 52 50 ml median 42 ml compared with 15 25 ml median 6 in patients whose ct did not show swirl sign p 0 001 swirl sign was independent predictor of death at one month p 0 03 adjusted odds ratio 2 6 95 ci 1 1 6 and functional outcome at three months p 0 045 adjusted odds ratio 2 6 95 ci 1 02 6 5 as swirl sign showed to be an ominous sign we recommend identification of this sign in cases of ichs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1222, "text": "the aim of the study was to identify the predictors of brain death bd upon admission to the intensive care unit icu of comatose patients with spontaneous intracerebral hemorrhage ich patients admitted in our icu from 2002 to 2010 for spontaneous ich and placed under mechanical ventilation were retrospectively analyzed of the 72 patients 49 evolved to bd 39 died after withdrawal of life support and 12 were discharged alive the most discriminating characteristics to predict bd were included in two models model 1 contained 3 abolished brainstem responses adjusted odds ratios or 8 4 2 4 29 1 and the swirl sign on the baseline ct scan adjusted or 5 0 1 6 15 9 and model 2 addressed the abolition of corneal reflexes unilateral bilateral adjusted or 4 2 0 9 20 1 8 8 2 4 32 3 and the swirl sign on the baseline ct scan adjusted or 6 2 1 9 20 0 two scores predicting bd were created sensitivity 0 89 and 0 88 specificity 0 68 and 0 65 risk of evolution toward bd was classified as low corneal reflexes present and no swirl sign high 1 corneal reflexes abolished and swirl sign and intermediate simple signs at icu admission can predict bd in comatose patients with ich and could increase the potential for organ donation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517301", "endSection": "abstract" } ] }, { "body": "What is Morgellons disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21749875", "http://www.ncbi.nlm.nih.gov/pubmed/27269255", "http://www.ncbi.nlm.nih.gov/pubmed/16489838", "http://www.ncbi.nlm.nih.gov/pubmed/28665169", "http://www.ncbi.nlm.nih.gov/pubmed/21437061", "http://www.ncbi.nlm.nih.gov/pubmed/27789971", "http://www.ncbi.nlm.nih.gov/pubmed/25879673", "http://www.ncbi.nlm.nih.gov/pubmed/21390982", "http://www.ncbi.nlm.nih.gov/pubmed/29052453", "http://www.ncbi.nlm.nih.gov/pubmed/28392653", "http://www.ncbi.nlm.nih.gov/pubmed/28299553", "http://www.ncbi.nlm.nih.gov/pubmed/21110523", "http://www.ncbi.nlm.nih.gov/pubmed/23326202", "http://www.ncbi.nlm.nih.gov/pubmed/25192328", "http://www.ncbi.nlm.nih.gov/pubmed/24671866" ], "ideal_answer": [ "It is a skin condition in which individuals have skin lesions that contain some kind of fibers. Patients often complain of bugs crawling under their skin. The disease is of unknown origin and may be psychosomatic, however recent evidence indicates it could be transmitted by a tick." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D055535", "http://www.disease-ontology.org/api/metadata/DOID:37" ], "type": "summary", "id": "5a74e6eb0384be9551000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "\"Morgellons disease\" has been a controversial topic in the history of psychodermatology. The most consensual scientific opinion is that it is a primary psychiatric disorder, particularly, a delusional disorder, although others were also pointed out. Some authors have suggested that it may correspond to a common dermatosis with secondary psychopathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28299553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Morgellons disease is a rare disease with unknown etiology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28392653", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 438, "text": "In recent years, there has been a reported increase in affliction of the skin with small fibres or other particles. The condition has been referred to as Morgellons disease. Patients present with stinging, burning or crawling sensations of the skin, with perceived extrusion of inanimate material alongside fatigue and other systemic symptoms. Sufferers often experience significant morbidity and reduction in quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28665169", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 651, "text": "including delusional infestation, Morgellons syndrome, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29052453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 446, "text": "Morgellons disease (MD) is a dermopathy characterized by multicolored filaments that lie under, are embedded in, or project from skin. Although MD was initially considered to be a delusional disorder, recent studies have demonstrated that the dermopathy is associated with tickborne infection, that the filaments are composed of keratin and collagen, and that they result from proliferation of keratinocytes and fibroblasts in epithelial tissue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789971", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 561, "text": "Morgellons disease (MD) is a complex skin disorder characterized by ulcerating lesions that have protruding or embedded filaments. Many clinicians refer to this condition as delusional parasitosis or delusional infestation and consider the filaments to be introduced textile fibers. In contrast, recent studies indicate that MD is a true somatic illness associated with tickborne infection, that the filaments are keratin and collagen in composition and that they result from proliferation and activation of keratinocytes and fibroblasts in the skin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25879673", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Morgellons is a medically contested diagnosis with foremost dermatological symptoms. Patients experience fibers emerging from the skin, together with a range of other somatic, psychiatric, and neurological complaints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24671866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Morgellons Disease is a condition involving painful skin lesions, fibrous growths protruding from the skin, and subcutaneous stinging and burning sensations, along with symptoms of anxiety, depression, fatigue, and memory and attention deficits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21390982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Morgellons disease is characterized by complaints of uncomfortable skin sensations and fibers emanating from nonhealing skin lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25192328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Morgellons disease is a controversial and poorly defined symptom cluster of skin lesions and somatic symptoms, most notably 'fibers' in the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21110523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Morgellons disease is a psycho-dermatologic condition in which patients report fibers or filaments \"growing\" out of their skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Morgellons disease is an infrequent syndromic condition, that typically affects middle-aged white women, characterized by crawling sensations on and under the skin, associated with itchy rashes, stinging sores, fiber-like filaments emerging from the sores, severe fatigue, concentrating difficulty, and memory loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269255", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 205, "text": "Morgellons disease is a controversial illness in which patients complain of stinging, burning, and biting sensations under the skin. Unusual subcutaneous fibers are the unique objective finding", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21437061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Morgellons disease is a mysterious skin disorder that was first described more than 300 years ago. The disease is characterized by fiber-like strands extruding from the skin in conjunction with various dermatologic and neuropsychiatric symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16489838", "endSection": "abstract" } ] }, { "body": "What is Cellbase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22693220", "http://www.ncbi.nlm.nih.gov/pubmed/28535294" ], "ideal_answer": [ "CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources.", "Cellbase is a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources. CellBase documentation can be found at http://docs.bioinfo.cipf.es/projects/cellbase.", "CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources. CellBase provides a solution to the growing necessity of integration by easing the access to biological data.", "CellBase is a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources." ], "type": "summary", "id": "5a6a2bbcb750ff4455000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693220", "endSection": "title" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1285, "text": "CellBase provides a solution to the growing necessity of integration by easing the access to biological data. CellBase implements a set of RESTful web services that query a centralized database containing the most relevant biological data sources. The database is hosted in our servers and is regularly updated. CellBase documentation can be found at http://docs.bioinfo.cipf.es/projects/cellbase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693220", "endSection": "title" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1135, "text": "CellBase implements a set of RESTful web services that query a centralized database containing the most relevant biological data sources.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1285, "text": "During the past years, the advances in high-throughput technologies have produced an unprecedented growth in the number and size of repositories and databases storing relevant biological data. Today, there is more biological information than ever but, unfortunately, the current status of many of these repositories is far from being optimal. Some of the most common problems are that the information is spread out in many small databases; frequently there are different standards among repositories and some databases are no longer supported or they contain too specific and unconnected information. In addition, data size is increasingly becoming an obstacle when accessing or storing biological data. All these issues make very difficult to extract and integrate information from different sources, to analyze experiments or to access and query this information in a programmatic way. CellBase provides a solution to the growing necessity of integration by easing the access to biological data. CellBase implements a set of RESTful web services that query a centralized database containing the most relevant biological data sources. The database is hosted in our servers and is regularly updated. CellBase documentation can be found at http://docs.bioinfo.cipf.es/projects/cellbase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "cellbase a comprehensive collection of restful web services for retrieving relevant biological information from heterogeneous sources", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22693220", "endSection": "title" }, { "offsetInBeginSection": 771, "offsetInEndSection": 935, "text": "HGVA calculates population frequencies for these projects and enriches their data with variant annotation provided by CellBase, a rich and fast annotation solution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28535294", "endSection": "abstract" } ] }, { "body": "What is the asosciation between the eustachian tube and the palatine muscle of the uvula?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10591352" ], "ideal_answer": [ "Palatal musculature is known to be responsible for the active opening of the eustachian tube. ", "The palatine musculature is involved in the opening of the eustachian tube.", "Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube", " Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube", "Palatal musculature is known to be responsible for the active opening of the eustachian tube. ", "Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube. " ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D005064", "https://meshb.nlm.nih.gov/record/ui?ui=D014609", "http://www.disease-ontology.org/api/metadata/DOID:12358" ], "type": "summary", "id": "5a897729fcd1d6a10c000009", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 301, "text": "Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube. Because laser-assisted uvulopalatoplasty (LAUP) may involve partial division of these muscles, the effect of this procedure on middle ear pressures (MEPs) and middle ear volumes (MEVs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10591352", "endSection": "abstract" } ] }, { "body": "Are Conserved Nonexonic Elements (CNEEs) important in phylogenomics research?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28417603", "http://www.ncbi.nlm.nih.gov/pubmed/28637293" ], "ideal_answer": [ "Yes. Conserved Nonexonic Elements (CNEEs) appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis." ], "exact_answer": "yes", "type": "yesno", "id": "5a6e18d8b750ff4455000038", "snippets": [ { "offsetInBeginSection": 1555, "offsetInEndSection": 1865, "text": "Overall, CNEEs appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28637293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Conserved Nonexonic Elements: A Novel Class of Marker for Phylogenomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28637293", "endSection": "title" }, { "offsetInBeginSection": 316, "offsetInEndSection": 583, "text": "Target capture for vertebrate animals is currently dominated by two approaches-anchored hybrid enrichment (AHE) and ultraconserved elements (UCE)-and both approaches have proven useful for addressing questions in phylogenomics, phylogeography and population genomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28417603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "conserved nonexonic elements a novel class of marker for phylogenomics", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28637293", "endSection": "title" } ] }, { "body": "What is the definition of General Regulatory Factors (GRFs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21914852", "http://www.ncbi.nlm.nih.gov/pubmed/28158860", "http://www.ncbi.nlm.nih.gov/pubmed/22889666", "http://www.ncbi.nlm.nih.gov/pubmed/17158163", "http://www.ncbi.nlm.nih.gov/pubmed/20371324", "http://www.ncbi.nlm.nih.gov/pubmed/25215414", "http://www.ncbi.nlm.nih.gov/pubmed/27262581", "http://www.ncbi.nlm.nih.gov/pubmed/28448767", "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "http://www.ncbi.nlm.nih.gov/pubmed/27540088", "http://www.ncbi.nlm.nih.gov/pubmed/27601258", "http://www.ncbi.nlm.nih.gov/pubmed/21081559" ], "ideal_answer": [ "GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains.", "In Saccharomyces cerevisiae, a group of more than 200 co-regulated genes (Ribi genes) is involved in ribosome biogenesis. This regulon has been shown to rely on a small set of transcriptional regulators (mainly Abf1, but also Reb1, Tbf1 and Rap1) referred to as general regulatory factors (GRFs) because of their widespread binding and action at many promoters and other specialized genomic regions.", "General regulatory factors (GRFs) as genome partitioners GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains. Abf1 and Rap1 are general regulatory factors (GRFs) that contribute to transcriptional activation of a large number of genes, as well as to replication, silencing and telomere structure in yeast. ", "We speculate that an important function of general regulatory factors such as Reb1p is to establish and maintain proper transcription start sites at promoters, and that when binding of such factors is compromised, resulting effects on mRNA translation may be an underappreciated aspect of gene regulation studies. We found that nucleosomes and specific DNA-binding proteins, including the general regulatory factors Reb1p, Rap1p, and Abf1p, and Pol III transcription factors enhance the efficiency of NNS termination by physically blocking Pol II progression. In the model organism Saccharomyces cerevisiae, these regions are adjacent to binding sites for general regulatory transcription factors, and the Reb1 protein is commonly bound to promoter DNA near such regions. Here, we use high resolution tiling arrays to examine the contributions of two general regulatory factors, Abf1 and Rap1, to nucleosome occupancy in Saccharomyces cerevisiae. Multiple roles of the general regulatory factor Abf1 in yeast ribosome biogenesis. GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains. " ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D035165", "https://meshb.nlm.nih.gov/record/ui?ui=D053263" ], "type": "summary", "id": "5a85a0f1faa1ab7d2e000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "General regulatory factors (GRFs) as genome partitioners", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "title" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1088, "text": "GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Abf1 and Rap1 are general regulatory factors (GRFs) that contribute to transcriptional activation of a large number of genes, as well as to replication, silencing and telomere structure in yeast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Extensive role of the general regulatory factors, Abf1 and Rap1, in determining genome-wide chromatin structure in budding yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081559", "endSection": "title" }, { "offsetInBeginSection": 471, "offsetInEndSection": 645, "text": "Here, we use high resolution tiling arrays to examine the contributions of two general regulatory factors, Abf1 and Rap1, to nucleosome occupancy in Saccharomyces cerevisiae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081559", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 954, "text": "These factors have each been shown to bind to a few hundred promoters, but we find here that thousands of loci show localized regions of altered nucleosome occupancy within 1 h of loss of Abf1 or Rap1 binding, and that altered chromatin structure can occur via binding sites having a wide range of affinities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081559", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 579, "text": "We found that nucleosomes and specific DNA-binding proteins, including the general regulatory factors (GRFs) Reb1p, Rap1p, and Abf1p, and Pol III transcription factors enhance the efficiency of NNS termination by physically blocking Pol II progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27540088", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 316, "text": " In the model organism Saccharomyces cerevisiae, these regions are adjacent to binding sites for general regulatory transcription factors, and the Reb1 protein is commonly bound to promoter DNA near such regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27601258", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1637, "text": "We speculate that an important function of general regulatory factors such as Reb1p is to establish and maintain proper transcription start sites at promoters, and that when binding of such factors is compromised, resulting effects on mRNA translation may be an underappreciated aspect of gene regulation studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27601258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Abf1 and other general regulatory factors control ribosome biogenesis gene expression in budding yeast", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28158860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Multiple roles of the general regulatory factor Abf1 in yeast ribosome biogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27262581", "endSection": "title" }, { "offsetInBeginSection": 539, "offsetInEndSection": 881, "text": " This observation changes the paradigm of general regulatory factors as relatively static DNA-binding proteins constitutively bound to highly active promoters, and point to Abf1, which binds hundreds of non-RPG promoters within the yeast genome, as a possible key regulatory switch in nutrient- and stress-dependent transcriptional modulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27262581", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1088, "text": "Insulators are sequences that uncouple adjacent chromosome domains. Here we have shown that Saccharomyces cerevisiae Rap1p and Abf1p proteins are endowed with a potent insulating capacity. Insulating domains in Rap1p coincide with previously described transcription activation domains, whereas four adjacent subdomains spanning the whole of the Abf1p C terminus (440-731) were found to display autonomous insulating capacity. That both Rap1p and Abf1p silencing domains either contain or largely overlap with an insulating domain suggests that insulation conveys some undefined chromosome organization capacity that also contributes a function in silencing. Together with Reb1p and Tbf1p, previously involved in the activity of Saccharomyces cerevisiae subtelomeric insulators, insulating potential emerges as a supplementary common property of General Regulatory Factors (GRFs). Thus GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 420, "text": "In Saccharomyces cerevisiae, a group of more than 200 co-regulated genes (Ribi genes) is involved in ribosome biogenesis. This regulon has recently been shown to rely on a small set of transcriptional regulators (mainly Abf1, but also Reb1, Tbf1 and Rap1) previously referred to as general regulatory factors (GRFs) because of their widespread binding and action at many promoters and other specialized genomic regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28448767", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 879, "text": "Together with Reb1p and Tbf1p, previously involved in the activity of Saccharomyces cerevisiae subtelomeric insulators, insulating potential emerges as a supplementary common property of General Regulatory Factors (GRFs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "General regulatory factors (GRFs) as genome partitioners.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "title" }, { "offsetInBeginSection": 122, "offsetInEndSection": 419, "text": "This regulon has recently been shown to rely on a small set of transcriptional regulators (mainly Abf1, but also Reb1, Tbf1 and Rap1) previously referred to as general regulatory factors (GRFs) because of their widespread binding and action at many promoters and other specialized genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28448767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Abf1 and Rap1 are general regulatory factors (GRFs) that contribute to transcriptional activation of a large number of genes, as well as to replication, silencing and telomere structure in yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158163", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1088, "text": "Thus GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1092, "text": "Thus GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Gene-regulation functions (GRF) provide a unique characteristic of a cis-regulatory module (CRM), relating the concentrations of transcription factors (input) to the promoter activities (output).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20371324", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 1381, "text": "Several general conclusions have been drawn: 1), long-range interactions, multilayer assembly and DNA looping may lead to complex GRFs that cannot be described by linear functions of binding site occupancies; 2), in general, GRFs cannot be described by the Boolean logic, whereas a three-state non-Boolean logic suffices for the studied examples; 3), studied CRMs of the intact phages seemed to have a similar GRF topology (the number of plateaus and peaks corresponding to different expression regimes); we hypothesize that functionally equivalent CRMs might have topologically equivalent GRFs for a larger class of genetic systems; and 4) within a given GRF class, a set of mechanistic-to-mathematical transformations has been identified, which allows shaping the GRF before carrying out a system-level analysis.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20371324", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 580, "text": "We found that nucleosomes and specific DNA-binding proteins, including the general regulatory factors (GRFs) Reb1p, Rap1p, and Abf1p, and Pol III transcription factors enhance the efficiency of NNS termination by physically blocking Pol II progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27540088", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 298, "text": "Here, we will focus on the roles of gene regulatory factors (GRFs), in particular transcription factors (TFs) and long non-coding RNAs (lncRNAs) during human evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25215414", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1208, "text": "Our approach reveals that the specific sequences bound by GRFs have diverged substantially across evolution, corresponding to a number of major evolutionary transitions in the repertoire of GRFs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21914852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 786, "text": "In Saccharomyces cerevisiae, a group of more than 200 co-regulated genes (Ribi genes) is involved in ribosome biogenesis. This regulon has recently been shown to rely on a small set of transcriptional regulators (mainly Abf1, but also Reb1, Tbf1 and Rap1) previously referred to as general regulatory factors (GRFs) because of their widespread binding and action at many promoters and other specialized genomic regions. Intriguingly, Abf1 binding to Ribi genes is differentially modulated in response to distinct nutrition signaling pathways. Such a dynamic promoter association has the potential to orchestrate both activation and repression of Ribi genes in synergy with neighboring regulatory sites and through the functional interplay of histone acetyltransferases and deacetylases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28448767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 746, "text": "Deciphering the molecular basis of how modern human phenotypes have evolved is one of the most fascinating challenges in biology. Here, we will focus on the roles of gene regulatory factors (GRFs), in particular transcription factors (TFs) and long non-coding RNAs (lncRNAs) during human evolution. We will present examples of TFs and lncRNAs that have changed or show signs of positive selection in humans compared to chimpanzees, in modern humans compared to archaic humans, or within modern human populations. On the basis of current knowledge about the functions of these GRF genes, we speculate that they have been involved in speciation as well as in shaping phenotypes such as brain functions, skeletal morphology, and metabolic processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25215414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1692, "text": "the packaging of eukaryotic genomes into nuclesomes plays critical roles in chromatin organization and gene regulation studies in saccharomyces cerevisiae indicate that nucleosome occupancy is partially encoded by intrinsic antinucleosomal dna sequences such as poly a sequences as well as by binding sites for trans acting factors that can evict nucleosomes such as reb1 and the rsc3 30 complex here we use genome wide nucleosome occupancy maps in 13 ascomycota fungi to discover large scale evolutionary reprogramming of both intrinsic and trans determinants of chromatin structure we find that poly g s act as intrinsic antinucleosomal sequences comparable to the known function of poly a s but that the abundance of poly g s has diverged greatly between species obscuring their antinucleosomal effect in low poly g species such as s cerevisiae we also develop a computational method that uses nucleosome occupancy maps for discovering trans acting general regulatory factor grf binding sites our approach reveals that the specific sequences bound by grfs have diverged substantially across evolution corresponding to a number of major evolutionary transitions in the repertoire of grfs we experimentally validate a proposed evolutionary transition from cbf1 as a major grf in pre whole genome duplication wgd yeasts to reb1 in post wgd yeasts we further show that the mating type switch activating protein sap1 is a grf in s pombe demonstrating the general applicability of our approach our results reveal that the underlying mechanisms that determine in vivo chromatin organization have diverged and that comparative genomics can help discover new determinants of chromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21914852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1370, "text": "rna polymerase ii pol ii transcription termination by the nrd1p nab3p sen1p nns pathway is critical for the production of stable noncoding rnas and the control of pervasive transcription in saccharomyces cerevisiae to uncover determinants of nns termination we mapped the 3 ends of nns terminated transcripts genome wide we found that nucleosomes and specific dna binding proteins including the general regulatory factors grfs reb1p rap1p and abf1p and pol iii transcription factors enhance the efficiency of nns termination by physically blocking pol ii progression the same dna bound factors that promote nns termination were shown previously to define the 3 ends of okazaki fragments synthesized by pol \u03b4 during dna replication reduced binding of these factors results in defective nns termination and pol ii readthrough furthermore inactivating nns enables pol ii elongation through these roadblocks demonstrating that effective pol ii termination depends on a synergy between the nns machinery and obstacles in chromatin consistent with this finding loci exhibiting pol ii readthrough at grf binding sites are depleted for upstream nns signals overall these results underscore how rna termination signals influence the behavior of pol ii at chromatin obstacles and establish that common genomic elements define boundaries for both dna and rna synthesis machineries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27540088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1284, "text": "ribosome biogenesis in saccharomyces cerevisiae involves a regulon of 200 genes ribi genes coordinately regulated in response to nutrient availability and cellular growth rate two cis acting elements called pac and rrpe are known to mediate ribi gene repression in response to nutritional downshift here we show that most ribi gene promoters also contain binding sites for one or more general regulatory factors grfs most frequently abf1 and reb1 and that these factors are enriched in vivo at ribi promoters abf1 reb1 tbf1 promoter association was required for full ribi gene expression in rich medium and for its modulation in response to glucose starvation characterized by a rapid drop followed by slow recovery such a response did not entail changes in abf1 occupancy but it was paralleled by a quick increase followed by slow decrease in rpd3l histone deacetylase occupancy remarkably abf1 site disruption also abolished rpd3l complex recruitment in response to starvation extensive mutational analysis of the dbp7 promoter revealed a complex interplay of tbf1 sites pac and rrpe in the transcriptional regulation of this ribi gene our observations point to grfs as new multifaceted players in ribi gene regulation both during exponential growth and under repressive conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28158860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1233, "text": "abf1 and rap1 are general regulatory factors grfs that contribute to transcriptional activation of a large number of genes as well as to replication silencing and telomere structure in yeast in spite of their widespread roles in transcription the scope of their functional targets genome wide has not been previously determined here we use microarrays to examine the contribution of these essential grfs to transcription genome wide by using ts mutants that dissociate from their binding sites at 37 degrees c we then combine this data with published chip chip studies and motif analysis to identify probable direct targets for abf1 and rap1 we also identify a substantial number of genes likely to bind rap1 or abf1 but not affected by loss of grf binding interestingly the results strongly suggest that rap1 can contribute to gene activation from farther upstream than can abf1 also consistent with previous work more genes that bind abf1 are unaffected by loss of binding than those that bind rap1 finally we show for several such genes that the abf1 c terminal region which contains the putative activation domain is not needed to confer this peculiar memory effect that allows continued transcription after loss of abf1 binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158163", "endSection": "abstract" } ] }, { "body": "Which virus can be diagnosed with the monospot test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28130396", "http://www.ncbi.nlm.nih.gov/pubmed/11369969", "http://www.ncbi.nlm.nih.gov/pubmed/1295944", "http://www.ncbi.nlm.nih.gov/pubmed/22123662", "http://www.ncbi.nlm.nih.gov/pubmed/24650116", "http://www.ncbi.nlm.nih.gov/pubmed/21045362", "http://www.ncbi.nlm.nih.gov/pubmed/24686796", "http://www.ncbi.nlm.nih.gov/pubmed/6270614", "http://www.ncbi.nlm.nih.gov/pubmed/21886730", "http://www.ncbi.nlm.nih.gov/pubmed/26275628", "http://www.ncbi.nlm.nih.gov/pubmed/28761605" ], "ideal_answer": [ "Epstein-Barr virus (EBV) can be detected with the monospot test. EBV is a highly prevalent virus, transmitted via saliva, which often causes asymptomatic infection in children but frequently results in infectious mononucleosis in adolescents." ], "exact_answer": [ "Epstein-Barr virus" ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0009597", "https://meshb.nlm.nih.gov/record/ui?ui=D003933", "https://meshb.nlm.nih.gov/record/ui?ui=D014780" ], "type": "factoid", "id": "5a690487b750ff445500001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 420, "text": "Epstein-Barr virus (EBV) is a highly prevalent virus, transmitted via saliva, which often causes asymptomatic infection in children but frequently results in infectious mononucleosis in adolescents. Heterophile antibody tests, including the Monospot test, are red cell or latex agglutination assays, which detect antired cell antibodies produced as part of a polyclonal antibody response occurring during EBV infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130396", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 828, "text": "Laboratory investigations revealed that monospot test was positive, EBV serology tests; Anti-EA-D Ig G: 3+, Anti-VCA gp125 Ig G: 3+, Anti-VCA p19 Ig M: 2+, Anti EBNA-1 Ig M: negative, Anti EBNA-1 Ig M: negative, Anti EBNA-1 Ig G: negative.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28761605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 547, "text": "A 75-year-old woman presented with altered mental status, septic picture, and influenza-like symptoms. Initial investigations revealed atypical lymphocytosis, thrombocytopenia, elevated liver enzymes, and a positive monospot test result. Further investigation showed the Epstein-Barr virus viral capsid antibody IgM/IgG and Epstein-Barr virus DNA by polymerase chain reaction to be negative; however, interestingly her cytomegalovirus (CMV) IgM and IgG were positive, suggesting that her mononucleosis-like syndrome was due to acute CMV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275628", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 974, "text": "Monospot test was positive. He subsequently had both a CT pulmonary angiogram and a CT angiogram of the aorta to exclude pulmonary embolism and aortic dissection. The CT revealed splenomegaly with a large subdiaphragmatic haematoma secondary to splenic rupture. This had likely caused referred pain through diaphragmatic irritation. He was taken to theatre for urgent splenectomy. The unifying diagnosis was infectious mononucleosis complicated by spontaneous splenic rupture secondary to Epstein-Barr virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24686796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 623, "text": "BACKGROUND: Infection with Epstein-Barr virus (EBV) is almost ubiquitous in humans and generally occurs at two ages: infantile, which is usually asymptomatic and associated with poorer socioeconomic conditions, and adolescent, which causes infectious mononucleosis (IM) in ~25% cases. The determinants of whether the infection causes IM remain uncertain. We aimed to evaluate seasonality and temporal trends in IM.METHODS: Data from all Monospot tests, used as a marker for IM, were collected from the Grampian population over 16 years.RESULTS: Positive Monospot test results peaked at 17 years in females and 19 in males. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650116", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 856, "text": "The evaluated diagnostic methods were real-time PCR (RT-PCR), IgM/IgG antibodies measured with different assays [measurement of Epstein-Barr virus viral load (EBV-VL) in peripheral blood, neutrophil/lymphocyte/monocyte counts, C-reactive protein values, and monospot test]. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22123662", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1099, "text": "Serological tests for EBV infection were consistent with acute infection (EBV virus capsid antigen was reactive with IgM and IgG antibodies). The Monospot test was also positive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21045362", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 821, "text": "Investigations revealed lymphocytosis and activated atypical lymphocytes in the peripheral smear, and positive monospot test. The boy subsequently recovered in one week with total disappearance of his rash. Epstein-Barr virus-related infectious mononucleosis was considered the most likely diagnosis for our patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21886730", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 576, "text": "Sera negative for the markers of both viruses: Hepatitis A (HAV) and Hepatitis B (HBV) were subsequently tested for IGM Heterophil antibodies against Epstein-Barr virus (EBV) by the Monospot slide test to diagnose acute infectious mononucleosis and tested for anti-CMV (IgM) by ELISA technique for the diagnosis of acute Cytomegalovirus (CMV) infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1295944", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 391, "text": "A serologic test for early antigen (EA) is more specific for diagnosing active EBV disease than the monospot or heterophile test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6270614", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 355, "text": "His septic screen was negative, but he had a positive Monospot test and immunoglobulin G for Epstein-Barr virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11369969", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 419, "text": "Heterophile antibody tests, including the Monospot test, are red cell or latex agglutination assays, which detect antired cell antibodies produced as part of a polyclonal antibody response occurring during EBV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130396", "endSection": "abstract" } ] }, { "body": "Why is the Fyn kinase considered a promising therapeutic target for Alzheimer's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28709498" ], "ideal_answer": [ "Fyn is an attractive target for AD therapeutics, not only based on its activation by A\u03b2 via cellular prion protein but also due to its known interaction with tau, uniquely linking the two key pathologies in AD." ], "type": "summary", "id": "5a774431faa1ab7d2e000004", "snippets": [ { "offsetInBeginSection": 1120, "offsetInEndSection": 1330, "text": "Fyn is an attractive target for AD therapeutics, not only based on its activation by A\u03b2 via cellular prion protein but also due to its known interaction with tau, uniquely linking the two key pathologies in AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28709498", "endSection": "abstract" } ] }, { "body": "What is the link between TADs and GRBs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28874668" ], "ideal_answer": [ "Topologically associating domains (TADs) are ancient features that coincide with Metazoan clusters of extreme noncoding conservation (aka GRBs).", "Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation" ], "type": "summary", "id": "5a67c8c4b750ff4455000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "title" }, { "offsetInBeginSection": 563, "offsetInEndSection": 901, "text": "clusters of CNEs strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1357, "text": "Metazoan genomes contain many clusters of conserved noncoding elements. Here, the authors provide evidence that these clusters coincide with distinct topologically associating domains in humans and Drosophila, revealing a conserved regulatory genomic architecture", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 735, "text": "Here, we show that clusters of CNEs strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 404, "text": "Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1358, "text": "Developmental genes in metazoan genomes are surrounded by dense clusters of conserved noncoding elements (CNEs). CNEs exhibit unexplained extreme levels of sequence conservation, with many acting as developmental long-range enhancers. Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs). Their function and distribution around important regulatory genes raises the question of how they relate to 3D conformation of these loci. Here, we show that clusters of CNEs strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation. The close correspondence between extreme noncoding conservation and TADs suggests that these TADs are ancient, revealing a regulatory architecture conserved over hundreds of millions of years.Metazoan genomes contain many clusters of conserved noncoding elements. Here, the authors provide evidence that these clusters coincide with distinct topologically associating domains in humans and Drosophila, revealing a conserved regulatory genomic architecture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "abstract" } ] }, { "body": "What is Target Explorer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12824372" ], "ideal_answer": [ "Target Explorer is an automated tool for the identification of new target genes for a specified set of transcription factors. It was specifically designed for the well-annotated Drosophila melanogaster genome, but most options can be used for sequences from other genomes as well. Target Explorer is available at http://trantor.bioc.columbia.edu/Target_Explorer/" ], "type": "summary", "id": "5a6a2f88b750ff4455000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Target Explorer: An automated tool for the identification of new target genes for a specified set of transcription factors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824372", "endSection": "title" }, { "offsetInBeginSection": 417, "offsetInEndSection": 901, "text": "Target Explorer automates the entire process from the creation of a customized library of binding sites for known transcription factors through the prediction and annotation of putative target genes that are potentially regulated by these factors. It was specifically designed for the well-annotated Drosophila melanogaster genome, but most options can be used for sequences from other genomes as well. Target Explorer is available at http://trantor.bioc.columbia.edu/Target_Explorer/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824372", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 664, "text": "Target Explorer automates the entire process from the creation of a customized library of binding sites for known transcription factors through the prediction and annotation of putative target genes that are potentially regulated by these factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 892, "text": "with the increasing number of eukaryotic genomes available high throughput automated tools for identification of regulatory dna sequences are becoming increasingly feasible several computational approaches for the prediction of regulatory elements were recently developed here we combine the prediction of clusters of binding sites for transcription factors with context information taken from genome annotations target explorer automates the entire process from the creation of a customized library of binding sites for known transcription factors through the prediction and annotation of putative target genes that are potentially regulated by these factors it was specifically designed for the well annotated drosophila melanogaster genome but most options can be used for sequences from other genomes as well target explorer is available at http trantor bioc columbia edu target explorer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "target explorer an automated tool for the identification of new target genes for a specified set of transcription factors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824372", "endSection": "title" } ] }, { "body": "Can the yeast protein Abf1 act as insulator?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12200417" ], "ideal_answer": [ "Saccharomyces cerevisiae Rap1p and Abf1p proteins are endowed with a potent insulating capacity", "yes", "Saccharomyces cerevisiae Rap1p and Abf1p proteins are endowed with a potent insulating capacity." ], "exact_answer": "yes", "type": "yesno", "id": "5a857bfffaa1ab7d2e000030", "snippets": [ { "offsetInBeginSection": 92, "offsetInEndSection": 187, "text": "Saccharomyces cerevisiae Rap1p and Abf1p proteins are endowed with a potent insulating capacity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 424, "text": "Insulating domains in Rap1p coincide with previously described transcription activation domains, whereas four adjacent subdomains spanning the whole of the Abf1p C terminus (440-731) were found to display autonomous insulating capacity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 658, "text": "That both Rap1p and Abf1p silencing domains either contain or largely overlap with an insulating domain suggests that insulation conveys some undefined chromosome organization capacity that also contributes a function in silencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12200417", "endSection": "abstract" } ] }, { "body": "What does the human IVIG treatment for Alzheimer's disease contain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25115546" ], "ideal_answer": [ "Human intravenous immunoglobulin (IVIG) is a mixture of polyclonal IgG antibodies isolated and pooled from thousands of healthy human donors." ], "type": "summary", "id": "5a7d535ffaa1ab7d2e000018", "snippets": [ { "offsetInBeginSection": 187, "offsetInEndSection": 328, "text": "Human intravenous immunoglobulin (IVIG) is a mixture of polyclonal IgG antibodies isolated and pooled from thousands of healthy human donors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25115546", "endSection": "abstract" } ] }, { "body": "Is there any linear-time and linear-space algorithm for the computation of avoided words in biological sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28293277" ], "ideal_answer": [ "Yes. There is a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x." ], "exact_answer": "yes", "type": "yesno", "id": "5a6d022ab750ff445500002a", "snippets": [ { "offsetInBeginSection": 1526, "offsetInEndSection": 1979, "text": "The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of lengthkin a given sequencex. We suggest a modification to this algorithm so that it computes all avoided words ofx, irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 468, "text": "We present a linear-time and linear-space algorithm for the computation of avoided words of length
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 364, "text": "BACKGROUND: The deviation of the observed frequency of a word
RESULTS: In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length
CONCLUSIONS: The systematic search for avoided words is particularly useful for biological sequence analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 436, "text": "We present a linear-time and linear-space algorithm for the computation of avoided words of length", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1770, "text": "We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 943, "text": "Hence, computing all such words na\u00efvely can be a very time-consuming procedure, in particular for large k. RESULTS In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length k in a given sequence of length n over a fixed-sized alphabet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1154, "text": "We also present a time-optimal [Formula: see text]-time algorithm to compute all [Formula: see text]-avoided words (of any length) in a sequence of length n over an integer alphabet of size [Formula: see text].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1867, "text": "the deviation of the observed frequency of a word from its expected frequency in a given sequence is used to determine whether or not the word is this concept is particularly useful in dna linguistic analysis the value of the deviation of denoted by formula see text effectively characterises the extent of a word by its edge contrast in the context in which it occurs a word of length formula see text is a formula see text avoided word in if formula see text for a given threshold formula see text notice that such a word may be completely from hence computing all such words na\u00efvely can be a very time consuming procedure in particular for large in this article we propose an formula see text time and formula see text space algorithm to compute all formula see text avoided words of length in a given sequence of length over a fixed sized alphabet we also present a time optimal formula see text time algorithm to compute all formula see text avoided words of any length in a sequence of length over an integer alphabet of size formula see text in addition we provide a tight asymptotic upper bound for the number of formula see text avoided words over an integer alphabet and the expected length of the longest one we make available an implementation of our algorithm experimental results using both real and synthetic data show the efficiency and applicability of our implementation in biological sequence analysis the systematic search for avoided words is particularly useful for biological sequence analysis we present a linear time and linear space algorithm for the computation of avoided words of length in a given sequence we suggest a modification to this algorithm so that it computes all avoided words of irrespective of their length within the same time complexity we also present combinatorial results with regards to avoided words and absent words.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293277", "endSection": "abstract" } ] }, { "body": "What is the mechanism of the auxin-inducible degron system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23836714", "http://www.ncbi.nlm.nih.gov/pubmed/28589221", "http://www.ncbi.nlm.nih.gov/pubmed/19915560", "http://www.ncbi.nlm.nih.gov/pubmed/21314938", "http://www.ncbi.nlm.nih.gov/pubmed/26081484", "http://www.ncbi.nlm.nih.gov/pubmed/27010248", "http://www.ncbi.nlm.nih.gov/pubmed/28680098", "http://www.ncbi.nlm.nih.gov/pubmed/25181302", "http://www.ncbi.nlm.nih.gov/pubmed/27052166" ], "ideal_answer": [ "Fusion of inducible degradation signals, so-called degrons, to cellular proteins is an elegant method of controlling protein levels in vivo. The auxin-inducible degron (AID) system allows the rapid and reversible proteolysis of proteins of interest, and enables the generation of conditional mutants of budding yeast. Strategies that use ubiquitin-mediated protein degradation to eliminate the product of a gene of interest, such as heat-inducible degron (td) and auxin-inducible degron (AID), are powerful methods for constructing conditional mutants. Auxin-inducible degron (AID) technology allows rapid depletion of proteins in animal cells and fungi, but its application to human cells has been limited by the difficulties of tagging endogenous proteins. The auxin-inducible degron harbors great potential for dynamic protein depletion in yeast. Here, we thoroughly and quantitatively characterize the auxin-inducible degron in single yeast cells.", "Plants have evolved a unique system in which the plant hormone auxin directly induces rapid degradation of the AUX/IAA family of transcription repressors by a specific form of the SCF E3 ubiquitin ligase. Other eukaryotes lack the auxin response but share the SCF degradation pathway, allowing the transplantation of the auxin-inducible degron (AID) system into nonplant cells and the use of a small molecule to conditionally control protein stability." ], "type": "summary", "id": "5a86bf2efaa1ab7d2e000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Fusion of inducible degradation signals, so-called degrons, to cellular proteins is an elegant method of controlling protein levels in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The auxin-inducible degron (AID) system allows the rapid and reversible proteolysis of proteins of interest, and enables the generation of conditional mutants of budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25181302", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 364, "text": "Strategies that use ubiquitin-mediated protein degradation to eliminate the product of a gene of interest, such as heat-inducible degron (td) and auxin-inducible degron (AID), are powerful methods for constructing conditional mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26081484", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 353, "text": "Auxin-inducible degron (AID) technology allows rapid depletion of proteins in animal cells and fungi, but its application to human cells has been limited by the difficulties of tagging endogenous proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27052166", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 462, "text": "The auxin-inducible degron harbors great potential for dynamic protein depletion in yeast. Here, we thoroughly and quantitatively characterize the auxin-inducible degron in single yeast cells. We show that an auxin concentration of 0.25\u2009mM is necessary for fast and uniform protein depletion between single cells, and that in mother cells proteins are depleted faster than their daughters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28680098", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 769, "text": "we introduce an easy and efficient method to generate conditional knockout cell lines based on combining auxin-inducible degron (AID) technology with CRISPR/Cas9 gene editing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 439, "text": "Plants have evolved a unique system in which the plant hormone auxin directly induces rapid degradation of the AUX/IAA family of transcription repressors by a specific form of the SCF E3 ubiquitin ligase. Other eukaryotes lack the auxin response but share the SCF degradation pathway, allowing us to transplant the auxin-inducible degron (AID) system into nonplant cells and use a small molecule to conditionally control protein stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19915560", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 757, "text": "We constructed an auxin-inducible degron (AID) system, which utilizes auxin-dependent poly-ubiquitination of Aux/IAA proteins by SCFTIR1 in plants, in fission yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21314938", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 757, "text": "RESULTS We constructed an auxin-inducible degron (AID) system, which utilizes auxin-dependent poly-ubiquitination of Aux/IAA proteins by SCFTIR1 in plants, in fission yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21314938", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1078, "text": "To this end, a degradation system was developed in yeast exploiting TIR1, a plant F box protein, which can recruit proteins with an auxin-inducible degron to an E3 ubiquitin ligase complex, but only in the presence of the phytohormone auxin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27010248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Plants have evolved a unique system in which the plant hormone auxin directly induces rapid degradation of the AUX/IAA family of transcription repressors by a specific form of the SCF E3 ubiquitin ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19915560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1661, "text": "inducible inactivation of a protein is a powerful approach for analysis of its function within cells fission yeast is a useful model for studying the fundamental mechanisms such as chromosome maintenance and cell cycle however previously published strategies for protein depletion are successful only for some proteins in some specific conditions and still do not achieve efficient depletion to cause acute phenotypes such as immediate cell cycle arrest the aim of this work was to construct a useful and powerful protein depletion system in shizosaccaromyces pombe we constructed an auxin inducible degron aid system which utilizes auxin dependent poly ubiquitination of aux iaa proteins by scftir1 in plants in fission yeast although expression of a plant f box protein tir1 decreased mcm4 aid a component of the mcm complex essential for dna replication tagged with aux iaa peptide depletion did not result in an evident growth defect we successfully improved degradation efficiency of mcm4 aid by fusion of tir1 with fission yeast skp1 a conserved f box interacting component of scf improved aid system i aid and the cells showed severe defect in growth the i aid system induced degradation of mcm4 aid in the chromatin bound mcm complex as well as those in soluble fractions the i aid system in conjunction with transcription repression off aid system we achieved more efficient depletion of other proteins including pol1 and cdc45 causing early s phase arrest improvement of the aid system allowed us to construct conditional null mutants of s pombe we propose that the off aid system is the powerful method for in vivo protein depletion in fission yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21314938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 786, "text": "plants have evolved a unique system in which the plant hormone auxin directly induces rapid degradation of the aux iaa family of transcription repressors by a specific form of the scf e3 ubiquitin ligase other eukaryotes lack the auxin response but share the scf degradation pathway allowing us to transplant the auxin inducible degron aid system into nonplant cells and use a small molecule to conditionally control protein stability the aid system allowed rapid and reversible degradation of target proteins in response to auxin and enabled us to generate efficient conditional mutants of essential proteins in yeast as well as cell lines derived from chicken mouse hamster monkey and human cells thus offering a powerful tool to control protein expression and study protein function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19915560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1370, "text": "the analysis of consequences resulting after experimental elimination of gene function has been and will continue to be an extremely successful strategy in biological research mutational elimination of gene function has been widely used in the fly drosophila melanogaster rna interference is used extensively as well in the fly exceptionally precise temporal and spatial control over elimination of gene function can be achieved in combination with sophisticated transgenic approaches and clonal analyses however the methods that act at the gene and transcript level cannot eliminate protein products which are already present at the time when mutant cells are generated or rna interference is started targeted inducible protein degradation is therefore of considerable interest for controlled rapid elimination of gene function to this end a degradation system was developed in yeast exploiting tir1 a plant f box protein which can recruit proteins with an auxin inducible degron to an e3 ubiquitin ligase complex but only in the presence of the phytohormone auxin here we demonstrate that the auxin inducible degradation system functions efficiently also in drosophila melanogaster neither auxin nor tir1 expression have obvious toxic effects in this organism and in combination they result in rapid degradation of a target protein fused to the auxin inducible degron.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27010248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1299, "text": "isolation of a tight conditional mutant of a gene of interest is an effective way of studying the functions of essential genes strategies that use ubiquitin mediated protein degradation to eliminate the product of a gene of interest such as heat inducible degron td and auxin inducible degron aid are powerful methods for constructing conditional mutants however these methods do not work with some genes here we describe an improved aid system iaid for isolating tight conditional mutants in the budding yeast saccharomyces cerevisiae in this method transcriptional repression by the tet off promoter is combined with proteolytic elimination of the target protein by the aid system to provide examples we describe the construction of tight mutants of the replication factors dpb11 and mcm10 dpb11 iaid and mcm10 iaid because dpb11 and mcm10 are required for the initiation of dna replication their tight mutants are unable to enter s phase this is the case for dpb11 iaid and mcm10 iaid cells after the addition of tetracycline and auxin both the tet off promoter and the aid system have been shown to work in model eukaryotes other than budding yeast therefore the iaid system is not only useful in budding yeast but also can be applied to other model systems to isolate tight conditional mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26081484", "endSection": "abstract" } ] }, { "body": "Which bacteria causes erythrasma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8469500", "http://www.ncbi.nlm.nih.gov/pubmed/18558055", "http://www.ncbi.nlm.nih.gov/pubmed/16719870", "http://www.ncbi.nlm.nih.gov/pubmed/25477907", "http://www.ncbi.nlm.nih.gov/pubmed/21977942", "http://www.ncbi.nlm.nih.gov/pubmed/12010076", "http://www.ncbi.nlm.nih.gov/pubmed/3965026", "http://www.ncbi.nlm.nih.gov/pubmed/25815650", "http://www.ncbi.nlm.nih.gov/pubmed/9614412", "http://www.ncbi.nlm.nih.gov/pubmed/18937649", "http://www.ncbi.nlm.nih.gov/pubmed/21393451", "http://www.ncbi.nlm.nih.gov/pubmed/6859802" ], "ideal_answer": [ "Corynebacterium minutissimum is the bacteria that leads to cutaneous eruptions of erythrasma and is the most common cause of interdigital foot infections." ], "exact_answer": [ "Corynebacterium minutissimum" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004894", "http://www.disease-ontology.org/api/metadata/DOID:4131", "https://meshb.nlm.nih.gov/record/ui?ui=D001419" ], "type": "factoid", "id": "5a68f448b750ff4455000018", "snippets": [ { "offsetInBeginSection": 115, "offsetInEndSection": 206, "text": "Erythrasma caused by Corynebacterium minutissimum can be confused with superficial mycoses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25477907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Exogenous coproporphyrin III production by Corynebacterium aurimucosum and Microbacterium oxydans in erythrasma lesions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21393451", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Erythrasma is a superficial skin disease caused by Gram-positive Corynebacterium species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21393451", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 387, "text": "AIM: To study a series of demographic features of patients suffering from pitted keratolysis, and to present a review of the Corynebacterium-associated infections, including pitted keratolysis, erythrasma, and trichobacteriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18937649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Corynebacterium minutissimum is the bacteria that leads to cutaneous eruptions of erythrasma and is the most common cause of interdigital foot infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12010076", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 333, "text": "Bacterial skin infections caused by corynebacteria include erythrasma, trichomycosis axillaris and pitted keratolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9614412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Corynebacterium minutissimum is the bacteria that leads to cutaneous eruptions of erythrasma and is the most common cause of interdigital foot infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12010076", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 473, "text": "Corynebacteria causes erythrasma, trichomycosis or pitted keratolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6859802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "BACKGROUND Erythrasma is a superficial skin infection caused by Corynebacterium minutissimum .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1105, "text": "skin infections are common and may be caused by bacteria fungi or viruses breaks in the skin integrity particularly those that inoculate pathogens into the dermis frequently cause or exacerbate skin infections bacterial skin infections caused by corynebacteria include erythrasma trichomycosis axillaris and pitted keratolysis staphylococci may cause impetigo ecthyma and folliculitis streptococcal skin infections include impetigo and erysipelas human papillomavirus skin infections present as several different types of warts depending on the surface infected and its relative moisture and the patterns of pressure the many dermatomycoses skin infections caused by fungi or yeasts include tinea capitis tinea barbae tinea cruris tinea manus tinea pedis and tinea unguium onychomycosis candidal infections occur in moist areas such as the vulva mouth penis skinfolds and diaper area wounds caused by wood splinters or thorns may result in sporotrichosis animal bites may result in complex serious infections requiring tetanus and possibly rabies prophylaxis in addition to appropriate antibiotic therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9614412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1210, "text": "erythrasma is a superficial skin disease caused by gram positive corynebacterium species coral red fluorescence under wood s light strongly suggestive of erythrasma can be attributed to the presence of porphyrins fractionated porphyrin analysis in erythrasma lesions is yet to be reported we attempted to investigate erythrasma lesions by isolating the responsible bacteria and determining their exogenous porphyrin production by hplc analysis we observed a 78 year old woman with erythrasma who had a well demarcated slightly scaling patch on her left foot between the fourth and fifth toes two kinds of colonies on 5 sheep blood agar were obtained from this lesion analysis of the 16s rrna sequence revealed the colonies to be corynebacterium aurimucosum and microbacterium oxydans hplc analysis demonstrated that coproporphyrin iii copro iii levels were clearly elevated although the amounts of protoporphyrin were diminished these results indicate that the fluorescent substance was copro iii this study supports the view that excess copro iii synthesis by c aurimucosum and m oxydans leads to accumulation of porphyrin in cutaneous tissue which emits a coral red fluorescence when exposed to wood s light.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21393451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1297, "text": "interdigital foot infections are mostly caused initially by dermatophytes yeasts and less frequently by bacteria erythrasma caused by corynebacterium minutissimum can be confused with superficial mycoses the aim of the study was to determine the prevalence of the etiologic agents of superficial mycoses and the frequency of corynebacterium minutissimum in interdigital foot infections all the samples obtained from the 121 patients with interdigital foot infections were examined directly with the use of 20 potassium hydroxide mounts and gram stain under the microscope and cultured on sabouraud s dextrose agar plates in identification of superficial mycoses the rate was found to be 14 with the cultural method and 14 with direct microscopic examination using a combination of direct microscopic examination and culture a 33 8 ratio was achieved in the culture of these samples the most isolated factor was trichophyton rubrum 33 7 in 24 of the patients 19 8 corynebacterium minutissimum was detected by gram staining in 6 of these patients trichophyton rubrum was found trichophyton mentagrophytes was found in 2 and trichosporon spp was found in 1 the examination of interdigital foot lesions in the laboratory the coexistence of erythrasma with dermatophytes and yeast should be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25477907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "exogenous coproporphyrin iii production by corynebacterium aurimucosum and microbacterium oxydans in erythrasma lesions", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21393451", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2119, "text": "corynebacterium minutissimum is the bacteria that leads to cutaneous eruptions of erythrasma and is the most common cause of interdigital foot infections it is found mostly in occluded intertriginous areas such as the axillae inframammary areas interspaces of the toes intergluteal and crural folds and is more common in individuals with diabetes mellitus than other clinical patients this organism can be isolated from a cutaneous site along with a concurrent dermatophyte or candida albicans infection the differential diagnosis of erythrasma includes psoriasis dermatophytosis candidiasis and intertrigo and methods for differentiating include wood s light examination and bacterial and mycological cultures erythromycin 250mg four times daily for 14 days is the treatment of choice and other antibacterials include tetracycline and chloramphenicol however the use of chloramphenicol is limited by bone marrow suppression potentially leading to neutropenia agranulocytosis and aplastic anaemia further studies are needed but clarithromycin may be an additional drug for use in the future where there is therapeutic failure or intertriginous involvement topical solutions such as clindamycin whitfield s ointment sodium fusidate ointment and antibacterial soaps may be required for both treatment and prophylaxis limited studies on the efficacy of these medications exist however systemic erythromycin demonstrates cure rates as high as 100 compared with tetracyclines systemic erythromycin has greater efficacy in patients with involvement of the axillae and groin and similar efficacy for interdigital infections whitfield s ointment has equal efficacy to systemic erythromycin in the axillae and groin but shows greater efficacy in the interdigital areas and is comparable with 2 sodium fusidate ointment for treatment of all areas adverse drug effects and potential drug interactions need to be considered no cost effectiveness data are available but there are limited data on cost related treatment issues a guideline is proposed for the detection evaluation treatment and prophylaxis of this cutaneous eruption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12010076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1382, "text": "erythrasma is a superficial skin infection caused by corynebacterium minutissimum interdigital erythrasma is the most common form and is easily confused with tinea pedis the aim of this study was to determine the prevalence of interdigital erythrasma in patients with clinically suspected tinea pedis this study was performed between january 1 2011 and january 31 2012 it included 182 patients who presented with concerns about interdigital lesions all of the patients were examined with a wood s lamp and smears were stained with gram s method direct examination with 20 potassium hydroxide was performed of 182 patients with interdigital lesions 73 40 1 were diagnosed as having erythrasma the mean sd age of the patients with erythrasma was 45 52 10 83 years range 22 70 years most of the patients with erythrasma were women 56 2 the most often clinical finding was desquamation using only wood s lamp examination or gram s staining resulted in 31 42 5 or 14 19 2 positive patients respectively using wood s lamp examination and gram s staining concurrently resulted in 28 positive patients 38 4 interdigital erythrasma is a common condition and can be difficult to differentiate from tinea pedis simple and rapid diagnosis can be made with wood s lamp examination but gram s staining is also a useful method especially in patients with negative wood s lamp examination findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 795, "text": "erythrasma is an uncommon vulvar infection best diagnosed by its fluorescence under the wood lamp this report shows that despite a negative wood lamp examination the diagnosis can be made histologically a 42 year old woman was referred to our clinic with a persistent candidal infection evaluation included a wood lamp examination wet mount and potassium hydroxide test of the affected skin all of which were negative a biopsy of the area demonstrated rods and filamentous organisms in the keratotic layer consistent with a corynebacterium minutissimum infection the patient was diagnosed as having erythrasma and she responded to oral erythromycin persistent vulvar diseases may be caused by erythrasma despite a negative wood lamp examination the diagnosis can be made by biopsy of the lesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8469500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1613, "text": "erythrasma is a skin infection which is caused by corynebacterium minutissimum interdigital erythrasma is the most common form the aim of this study was to detect the frequency and risk factors of interdigital erythrasma in patients with clinically suspected tinea pedis this study was conducted between june and december 2010 and included 122 patients who had interdigital foot lesions all patients were examined using a wood s lamp the smears were stained using gram s method direct examination was performed using 20 potassium hydroxide sabouraud dextrose agar and brain heart infusion agar were used for cultures moreover the demographical characteristics of patients concomitant diseases and clinical findings were also recorded cases that were found to be positive on wood s lamp examination and or gram staining culture were considered as erythrasma the rate of erythrasma was found to be 46 7 the mean age was 43 6 years and the disease was more prevalent in men the most common clinical finding was desquamation mycological examination was found as positive in 40 35 of the patients no growth was observed in bacteriological cultures it was found that using only wood s lamp examination or gram staining resulted in 11 9 and 19 positive patients 15 6 respectively whereas using both wood s lamp examination and gram staining concurrently resulted in 27 positive patients 22 1 interdigital erythrasma is a commonly seen condition and can clinically mimic tinea pedis a wood s lamp is a good diagnostic tool but gram staining particularly in those with a negative wood s lamp result may be a useful method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21977942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1771, "text": "erythrasma is a superficial infection caused by corynebacterium minutissimum and affects the major skin folds and the interdigital regions of the feet it is characterized by erythematous brown scaly patches and maceration and exhibits coral red fluorescence under wood light the aim of this study was to determine the frequency of erythrasma in patients with interdigital lesions an open prospective longitudinal observational study was performed in a hospital in mexico city between march and december 2006 all patients with interdigital lesions were examined with a wood lamp and direct examination was performed with 20 potassium hydroxide cultures were done in sabouraud dextrose agar and brain heart infusion agar and smears were analyzed general characteristics and concomitant diseases were recorded we examined 73 patients of whom 24 32 8 were diagnosed with erythrasma based on coral red fluorescence under wood light and identification of corynebacteria by gram staining the disease was more common in women 83 33 and the mean age of the patients was 43 5 years the main clinical findings were scaling and maceration and the fourth interdigital web was the most commonly affected corynebacterium could not be isolated in any of the cases mycology was positive in 15 cases 62 5 and the following microorganisms were isolated candida 16 6 dermatophytes 12 5 and trichosporon 4 1 interdigital erythrasma is a common condition and can be easily confused with interdigital tinea it persists if not treated appropriately rapid diagnosis is easily obtained by examination with a wood lamp while culture is difficult and unnecessary for diagnosis the coexistence of erythrasma with dermatophytes and candida should be considered when the interdigital webs are affected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18558055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1622, "text": "erythrasma is a superficial cutaneous infection caused by corynebacterium minutissimum and is characterized by fluorescence under wood s light uv because of the presence of porphyrins these molecules are photosensitizing and we propose to assess efficacy of red light that activates porphyrins photodynamic reaction in treatment of this pathology assessment of effects of photodynamic action of red light for treatment of erythrasma without exogenous photosensitizing molecules thirteen patients with erythrasma were treated by one illumination 80 j cm2 by red light broad band peak at 635 nm without exogenous photosensitizing molecules disappearance or reduction of extent of lesions were observed 2 weeks later if lesions were still present a second irradiation was conducted with the same method preliminary results are presented as a result of red light irradiation we noticed a complete recovery for three patients and in most other cases reduction of extent of lesions mean 29 after one session the treatment was well tolerated we report first cases of photodynamic treatment of erythrasma there are other reports of clinical applications of antimicrobial action of photodynamic therapy in dermatology acne vulgaris leishmaniasis warts etc but there are few applications without addition of exogenous photosensitizing agent the originality and interest of our study is to use spontaneous presence of porphyrins in the lesions this technique seems to be an interesting alternative inexpensive and easy for the treatment of this localized infection but an optimal method is still to be determined to improve efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16719870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 700, "text": "bacterial skin infections are important to recognize because we have the means to eradicate almost all of them primary skin infections are mainly caused by staphylococci or streptococci staphylococci infections present as furuncles and carbuncles superficial folliculitis impetigo or rarely the scalded skin syndrome streptococcal infections present as impetigo ecthyma erysipelas or cellulitis corynebacteria causes erythrasma trichomycosis or pitted keratolysis gram negative primary skin infections although uncommon may occur bacterial cultures are generally necessary for diagnosis secondary bacterial infections of pre existing wounds burns dermatitic skin or retention cysts are common events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6859802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 773, "text": "infective embolic retinopathy as a sequela of bacterial endocarditis is described in a 31 year old woman with mitral valve prolapse the infective organism corynebacterium minutissimum has not been previously found to cause ocular or multisystem diseases it is a common mucocutaneous inhabitant which causes erythrasma in our case report both ocular involvement and septicaemia were present the infection was confirmed by positive serial blood cultures mitral valve prolapse was confirmed by echocardiography on clinical examination the retinopathy consisted of white intraretinal lesions which resolved with antibiotic therapy by fluorescein angiography focal areas of hypofluorescence corresponding to the white fundus lesions were present optic disc oedema was also seen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3965026", "endSection": "abstract" } ] }, { "body": "Mutations in which gene cause Schimke immune-osseous dysplasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28623093", "http://www.ncbi.nlm.nih.gov/pubmed/25748404", "http://www.ncbi.nlm.nih.gov/pubmed/16237566", "http://www.ncbi.nlm.nih.gov/pubmed/11799392", "http://www.ncbi.nlm.nih.gov/pubmed/18520775", "http://www.ncbi.nlm.nih.gov/pubmed/23359635", "http://www.ncbi.nlm.nih.gov/pubmed/27411420", "http://www.ncbi.nlm.nih.gov/pubmed/16816006", "http://www.ncbi.nlm.nih.gov/pubmed/24589093", "http://www.ncbi.nlm.nih.gov/pubmed/27813696", "http://www.ncbi.nlm.nih.gov/pubmed/22378147" ], "ideal_answer": [ "SMARCAL1, also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia, an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. ", "Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage.", "Smarcal1 , also known as harp, is an atp-dependent annealing helicase that stabilizes replication forks during dna damage. Mutations in this gene are the cause of schimke immune-osseous dysplasia , an autosomal recessive disorder characterized by t-cell immunodeficiency and growth dysfunctions. ", "Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. ", "Mutations in this gene are the cause of Schimke immune-osseous dysplasia , an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. SMARCAL1 , also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. ", "SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions." ], "exact_answer": [ "SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1)", "HARP" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0060490" ], "type": "factoid", "id": "5a6e4d22b750ff445500004d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28623093", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 634, "text": "The present report describes, for the first time, a Schimke immuno-osseous dysplasia child with SMARCAL1 missense mutation (R561H) and manifestations of intussusception secondary to Epstein-Barr virus-negative non-Hodgkin lymphoma, who expired due to septicemia following chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359635", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 348, "text": "Mutations in SWI/SNF2 related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) gene are responsible for the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359635", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 776, "text": "Sequence analysis revealed that patient was compound heterozygous for two SMARCAL1 mutations: a novel missense change (p.Arg247Pro) and a well-known nonsense mutation (p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24589093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Mutations in SMARCAL1, which encodes a DNA annealing helicase with roles in DNA replication fork restart, DNA repair, and gene expression modulation, cause Schimke immuno-osseous dysplasia (SIOD), an autosomal recessive disease characterized by skeletal dysplasia, renal disease, T-cell immunodeficiency, and arteriosclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27813696", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22378147", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A novel SMARCAL1 mutation associated with a mild phenotype of Schimke immuno-osseous dysplasia (SIOD).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24589093", "endSection": "title" }, { "offsetInBeginSection": 207, "offsetInEndSection": 256, "text": "SIOD is caused by mutations in the gene SMARCAL1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24589093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon autosomal-recessive multisystem disease caused by mutations in SMARCAL1 (swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), a gene encoding a putative chromatin remodeling protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18520775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Schimke immuno-osseous dysplasia is an autosomal recessive multisystem disorder caused by defects in SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 gene (SMARCAL1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27411420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Autosomal-recessive Schimke immuno-osseous dysplasia (SIOD) characterized by spondyloepiphyseal dysplasia, focal-segmental glomerulosclerosis (FSGS), T-cell immunodeficiency and facial dysmorphism is caused by defects in the SMARCAL1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16237566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "OBJECTIVE Schimke immuno-osseous dysplasia (SIOD), is an autosomal recessive inherited disease caused by SMARCAL1 (MIM:20606622) mutations, while in about half of the patients no any mutation in SMARCAL1 could be found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25748404", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 255, "text": "SIOD is caused by mutations in the gene SMARCAL1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24589093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "mutant chromatin remodeling protein smarcal1 causes schimke immuno osseous dysplasia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11799392", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "a novel smarcal1 mutation associated with a mild phenotype of schimke immuno osseous dysplasia siod", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24589093", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1695, "text": "schimke immuno osseous dysplasia is a rare autosomal recessive multisystem disorder with the main clinical features of disproportionate growth deficiency defective cellular immunity and progressive renal disease it is caused by mutations of smarcal1 a gene encoding a putative chromatin remodeling protein of unknown function because a detailed description of the clinical features is an essential first step in elucidating the function of smarcal1 we present the first detailed anthropometric data for schimke immuno osseous dysplasia patients by comprehensive anthropometric examination 28 parameters of 8 patients 3 females with the typical findings of schimke immuno osseous dysplasia mean age 14 8 years range 4 9 30 5 years and 304 patients 117 females with congenital and hereditary chronic kidney disease mean age 10 7 4 8 years range 3 21 8 years we show that schimke immuno osseous dysplasia patients differ significantly from those with other forms of chronic kidney disease z scores were calculated with reference limits derived from 5155 healthy children 2591 females aged 3 to 18 years the key finding was that in the latter group median leg length was significantly more reduced than sitting height whereas in schimke immuno osseous dysplasia patients the reduction of sitting height was significantly more pronounced than for leg length therefore the ratio of sitting height leg length might be a simple tool for the clinician to distinguish schimke immuno osseous dysplasia from other chronic kidney disease patients schimke immuno osseous dysplasia is very likely if this ratio is 0 83 however other forms of chronic kidney disease have to be discussed in case of a ratio 1 01.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16816006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 991, "text": "schimke immuno osseous dysplasia is an autosomal recessive multisystem disorder caused by defects in swi snf related matrix associated actin dependent regulator of chromatin subfamily a like 1 gene smarcal1 smarcal1 product is a helicase that has role in selective cellular proliferation the disorder is characterized by spondyloepiphyseal dysplasia with short stature nephropathy t cell deficiency neurologic and cutaneous signs patients may have hyperpigmented skin lesions similar to caf\u00e9 au lait spots symptoms and disease severity in schimke immuno osseous dysplasia varies from patient to patient genetic epigenetic and environmental factors play role on the severity of the disease here we report on a patient with short stature steroid resistant nephrotic syndrome and recurrent infections cutaneous findings and developmental delay helped us to reach the diagnosis of schimke immuno osseous dysplasia a homozygous missense mutation in smarcal1 gene confirmed the clinical diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27411420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1137, "text": "schimke immuno osseous dysplasia siod omim 242900 is an autosomal recessive pleiotropic disorder characterized by spondyloepiphyseal dysplasia renal dysfunction and t cell immunodeficiency siod is caused by mutations in the gene smarcal1 we report the clinical and genetic diagnosis of a 5 years old girl with siod referred to our center because of nephrotic range proteinuria occasionally detected during the follow up for congenital hypothyroidism mutational analysis of smarcal1 gene was performed by polymerase chain reaction pcr and bidirectional sequencing sequence analysis revealed that patient was compound heterozygous for two smarcal1 mutations a novel missense change p arg247pro and a well known nonsense mutation p glu848 this report provided the clinical and genetic description of a mild phenotype of schimke immuno osseous dysplasia associated with nephrotic proteinuria decreasing after combined therapy with ace inhibitors and sartans our experience highlighted the importance of detailed clinical evaluation appropriate genetic counseling and molecular testing to provide timely treatment and more accurate prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24589093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1817, "text": "schimke immuno osseous dysplasia siod is an autosomal recessive inherited disease caused by smarcal1 mim 20606622 mutations while in about half of the patients no any mutation in smarcal1 could be found this disease involves multiple systems and is characterized by short and dissymmetric stature with spondyloepiphyseal dysplasia progressive renal failure lymphopenia with recurrent infections and hyperpigmented macules this study aimed to analyze smarcal1 gene of 2 unrelated suspected siod children to make definite diagnosis and find more smarcal1 mutation types of chinese siod two suspected chinese han male siod children who visited our hospital from 2008 to 2014 aged 3 y 6 m and 7 y 8 m both were short and had spondyloepiphyseal dysplasia progressive renal failure lymphopenia with recurrent infections after informed consent they and their parents s dna were extracted from blood pcrs for all 16 exons of smarcal1 were performed and pcr products were purified by 2 gel electrophoresis and sequenced directly pathogenicity of missense variations was confirmed by sift and sequencing smarcal1 of fifty normal controls 1 four gene variations were found in the two children two reported missense mutations c 1129g c p glu377gln and c 1933c t p arg645cys two splicing mutations c 1334 1g a and c 2142 1 g a were detected 2 c 1129g c p glu377gln were reported as a disease causing mutations before but it was an single nucleotide polymorphism snp which was found in 15 of 50 normal controls 3 two novel splicing mutations were found in this study c 1334 1g a and c 2142 1 g a 1 we detected 3 disease causing mutations in 2 siod children by smarcal1 gene analysis while 2 splicing mutations were novel mutations 2 c 1129g c p glu377gln was a snp but not a disease causing mutation at least in chinese population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25748404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1279, "text": "mutations in smarcal1 which encodes a dna annealing helicase with roles in dna replication fork restart dna repair and gene expression modulation cause schimke immuno osseous dysplasia siod an autosomal recessive disease characterized by skeletal dysplasia renal disease t cell immunodeficiency and arteriosclerosis the clinical features of siod arise from pathological changes in gene expression however the underlying mechanism for these gene expression alterations remains unclear we hypothesized that changes of the epigenome alter gene expression in siod to test this we performed a genetic screen for interaction between marcal1 the drosophila melanogaster ortholog of smarcal1 and the genes of the trithorax group trxg and polycomb group pcg which encode epigenetic regulators smarcal1 and marcal1 genetically interacted with trxg and pcg members a homozygous null mutation of marcal1 suppressed the wing to haltere transformation ectopic ultrabithorax ubx expression and ectopic ubx minigene expression caused by pcg deficiency the suppression of ectopic ubx expression correlated with reduced chromatin accessibility of the ubx promoter to our knowledge this is the first in vivo evidence for deficiency of a smarcal1 ortholog altering the chromatin structure of a gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27813696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1674, "text": "autosomal recessive schimke immuno osseous dysplasia siod characterized by spondyloepiphyseal dysplasia focal segmental glomerulosclerosis fsgs t cell immunodeficiency and facial dysmorphism is caused by defects in the smarcal1 gene the gene product is involved in the transcriptional regulation of other genes a 12 year old boy of consanginous turkish descent developed disproportionate short stature from spondyloepiphyseal dysplasia at the age of 6 and nephrotic syndrome at the age of 10 years renal biopsy revealed fsgs the kidney function was normal t lymphocytes were diminished without infectious complications and he has had no cerebral ischemia analysis of the patient s smarcal1 gene revealed a novel homozygous c1798t transition leading to a r561c substitution the parents and two healthy sisters were found to be heterozygous a younger brother who is also homozygous for the mutation is clinically asymptomatic and has no proteinuria at the age of 18 months still his cd4 cells are diminished for smarcal1 mutations a clear genotype phenotype correlation has been reported severe siod with in utero or early childhood onset leading to end stage renal disease within a few years is caused by nonsense frame shift or splice mutations many patients die from infections and cerebrovascular insults during childhood mild siod manifests later and progresses more slowly without infectious or cerebral vascular complications the underlying defect being missense mutations in all three patients reported so far the novel r561c missense mutation in our patient with mild siod is additional evidence for the genotype phenotype correlation reported for smarcal1 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16237566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 780, "text": "schimke immuno osseous dysplasia is a rare autosomal recessive multisystem disorder characterized by steroid resistant nephrotic syndrome immunodeficiency and spondyloepiphyseal dysplasia mutations in swi snf2 related matrix associated actin dependent regulator of chromatin subfamily a like 1 smarcal1 gene are responsible for the disease the present report describes for the first time a schimke immuno osseous dysplasia child with smarcal1 missense mutation r561h and manifestations of intussusception secondary to epstein barr virus negative non hodgkin lymphoma who expired due to septicemia following chemotherapy the report emphasizes the necessity of more limited immunosuppressive protocols in schimke immuno osseous dysplasia patients with lymphoproliferative disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23359635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "The role of SMARCAL1 in replication fork stability and telomere maintenance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28623093", "endSection": "title" }, { "offsetInBeginSection": 331, "offsetInEndSection": 551, "text": "Because a detailed description of the clinical features is an essential first step in elucidating the function of SMARCAL1, we present the first detailed anthropometric data for Schimke-immuno-osseous dysplasia patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16816006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "smarcal1 gene analysis of 2 chinese schimke immuno osseous dysplasia children", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25748404", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "chromatin changes in smarcal1 deficiency a hypothesis for the gene expression alterations of schimke immuno osseous dysplasia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27813696", "endSection": "title" } ] }, { "body": "What is the most common histological diagnosis of \"butterfly glioma\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27521725", "http://www.ncbi.nlm.nih.gov/pubmed/17854667", "http://www.ncbi.nlm.nih.gov/pubmed/27458589", "http://www.ncbi.nlm.nih.gov/pubmed/1656290", "http://www.ncbi.nlm.nih.gov/pubmed/28361164", "http://www.ncbi.nlm.nih.gov/pubmed/9452242", "http://www.ncbi.nlm.nih.gov/pubmed/28936073" ], "ideal_answer": [ "Butterfly glioma is glioblastoma multiforme invading corpus callosum ." ], "exact_answer": [ "glioblastoma multiforme" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D003933" ], "type": "factoid", "id": "5a7234352dc08e987e000007", "snippets": [ { "offsetInBeginSection": 37, "offsetInEndSection": 101, "text": "Corpus callosum glioblastoma multiforme (GBM): butterfly glioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361164", "endSection": "title" }, { "offsetInBeginSection": 134, "offsetInEndSection": 282, "text": "The diagnosis of butterfly glioma (glioblastoma multiforme) was made based on imaging characteristics and was further confirmed by biopsy findings. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361164", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1143, "text": "Using Cox proportional hazards regression, the independent prognostic factors were Karnofsky Performance Status score \u226470, splenium involvement, and butterfly glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28936073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Canine Butterfly Glioblastomas: A Neuroradiological Review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458589", "endSection": "title" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1354, "text": "All tumors demonstrated classical histopathological features of glioblastoma multiforme (GBM), including glial cell pseudopalisading, serpentine necrosis, microvascular proliferation as well as invasion of the corpus callosum by neoplastic astrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Metastatic Adenoid Cystic Carcinoma Mimicking Butterfly Glioblastoma: A Rare Presentation in the Splenium of the Corpus Callosum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521725", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND: Intracranial spread of an adenoid cystic carcinoma (ACC) of the parotid gland is rare, and metastatic ACC to the splenium of the corpus callosum mimicking butterfly glioblastoma (GBM) has not been reported previously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Diverse molecular pattern in a bihemispheric glioblastoma (butterfly glioma) in a 16-year-old boy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17854667", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Glioblastoma multiforme (GBM), the most common malignant brain tumor of adults, is relatively rare in children. In a GBM affecting a 16-year-old boy, the tumor spread across the corpus callosum (butterfly glioma). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17854667", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 874, "text": "The original \"clearcut\" diagnosis of glioblastoma multiforme, based on CT scans, was unexpectedly disproved by examination of stereotactically obtained brain biopsy specimens, which revealed a neuronal ceroid lipofuscinosis (Kufs' disease). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9452242", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 281, "text": "The diagnosis of butterfly glioma (glioblastoma multiforme) was made based on imaging characteristics and was further confirmed by biopsy findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361164", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 686, "text": "In addition to a large butterfly glioblastoma originating from the frontal part of the corpus callosum, neuropathologic examination revealed a mycotic encephalitis with formation of numerous fungi-containing inflammatory foci in all parts of the brain and in the glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1656290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Corpus callosum glioblastoma multiforme (GBM): butterfly glioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361164", "endSection": "title" }, { "offsetInBeginSection": 1420, "offsetInEndSection": 1623, "text": "When a tumor with adenoid histological features and a \"butterfly\" phenotype grows in the corpus callosum in a patient with known parotid ACC, both metastasis and adenoid variant GBM should be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521725", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 213, "text": "In a GBM affecting a 16-year-old boy, the tumor spread across the corpus callosum (butterfly glioma).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17854667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "BACKGROUND Intracranial spread of an adenoid cystic carcinoma (ACC) of the parotid gland is rare, and metastatic ACC to the splenium of the corpus callosum mimicking butterfly glioblastoma (GBM) has not been reported previously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1275, "text": "the pathologies implicate the bilateral corpus callosum that builds the butterfly pattern on axial view these tumors have seldom been investigated for both clinical manifestations and outcome the objective of this study was to describe the clinical characteristics and outcomes of the butterfly tumor and to identify the predictive factors associated with survival outcome a retrospective study of 50 butterfly tumor was conducted between 2003 and 2016 the clinical characteristics imaging and outcome were assessed for the purpose of descriptive analysis using the kaplan meier method the median overall survival of the butterfly tumor was determined furthermore the cox proportional hazard regression was the estimated hazard ratio for death diffuse large b cell lymphoma was common of butterfly lesions the mortality rate was 78 and overall median survival time was 16 03 months 95 confidence interval 14 0 19 8 using cox proportional hazards regression the independent prognostic factors were karnofsky performance status score 70 splenium involvement and butterfly glioblastoma the butterfly tumor is a poor prognostic disease compared with each histology subgroup further molecular investigation is preferable to explore genetic variations associated with these tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28936073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 989, "text": "a 45 year old male with a butterfly glioma received stereotactic biopsy for histologic confirmation of the clinical diagnosis microscopically the results were controversial since some biopsy specimens showed distinct inflammatory changes while others displayed typical features of a malignant glioma the patient died four days after the stereotactic approach due to therapy resistant intracranial pressure rise in addition to a large butterfly glioblastoma originating from the frontal part of the corpus callosum neuropathologic examination revealed a mycotic encephalitis with formation of numerous fungi containing inflammatory foci in all parts of the brain and in the glioma general autopsy disclosed pulmonary aspergillosis as the source of the inflammatory spread a previous steroid medication over several weeks for treatment of increased intracranial pressure may be considered as an important factor in the origin of the pulmonary aspergillosis complicating the butterfly glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1656290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "clinics in diagnostic imaging 175 corpus callosum glioblastoma multiforme gbm butterfly glioma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361164", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 606, "text": "a 54 year old man presented with change in behaviour nocturnal enuresis abnormal limb movement and headache of one week s duration the diagnosis of butterfly glioma glioblastoma multiforme was made based on imaging characteristics and was further confirmed by biopsy findings as the corpus callosum is usually resistant to infiltration by tumours a mass that involves and crosses the corpus callosum is suggestive of an aggressive neoplasm other neoplastic and non neoplastic conditions that may involve the corpus callosum and mimic a butterfly glioma as well as associated imaging features are discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1651, "text": "intracranial spread of an adenoid cystic carcinoma acc of the parotid gland is rare and metastatic acc to the splenium of the corpus callosum mimicking butterfly glioblastoma gbm has not been reported previously we report a rare case of metastasis to the splenium of the corpus callosum from acc of the parotid gland the tumor occupied the splenium and mimicked the presentation of a butterfly glioma the patient had undergone parotidectomy 5 years before presentation with this intracranial lesion on magnetic resonance imaging the lesion was separate from the pineal gland and displaced the internal cerebral veins downward ventricular obstruction and increased cellularity were also suggested and multiple fluid filled cystic spaces were observed the tumor was partially resected because the extreme lateral boundary could not be visualized histological analysis with anti c kit antibody showed strong expression of the epithelial component immunohistochemistry with anti p63 antibody revealed nests of positive tumor cells highlighting the myoepithelial component the tumor also stained positive for anti myb antibody the treatment for this lesion is surgical debulking followed by radiation therapy however the overall prognosis remains grim because of limited chemotherapy options and a propensity for recurrence in both local and distant fashions when a tumor with adenoid histological features and a butterfly phenotype grows in the corpus callosum in a patient with known parotid acc both metastasis and adenoid variant gbm should be considered careful clinical and radiological correlation is required to diagnose and treat this rare lesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1055, "text": "the authors report a case of neuronal ceroid lipofuscinosis kufs disease confirmed by stereotactically obtained brain biopsy findings and initially diagnosed as a butterfly glioma the presenting symptoms in the 64 year old patient were mental alterations with progressive dementia followed by muscular atrophy and myoclonia with distal preponderance the mild initial disturbances of coordination increased and the patient developed a markedly ataxic gait computerized tomography ct scanning and magnetic resonance imaging revealed generalized cerebral atrophy and a bifrontal space occupying lesion involving the callosum the original clearcut diagnosis of glioblastoma multiforme based on ct scans was unexpectedly disproved by examination of stereotactically obtained brain biopsy specimens which revealed a neuronal ceroid lipofuscinosis kufs disease to the authors knowledge this is the first report of a case presenting with both diffuse brain atrophy and localized accumulation of neuronal lipofuscin mimicking a mass lesion on radiological studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9452242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "diverse molecular pattern in a bihemispheric glioblastoma butterfly glioma in a 16 year old boy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17854667", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "canine butterfly glioblastomas a neuroradiological review", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458589", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1038, "text": "glioblastoma multiforme gbm the most common malignant brain tumor of adults is relatively rare in children in a gbm affecting a 16 year old boy the tumor spread across the corpus callosum butterfly glioma this type of bilateral hemispheric growth has previously been thought to result from spread along the white matter tracts two samples obtained from opposite sides of the same tumor were analyzed comprehensively for loss of heterozygosity loh and microsatellite instability msi amplification of egfr and mdm2 was studied by means of multiplex polymerase chain reaction exons 5 6 7 and 8 of tp53 were screened for mutations by sequencing in neither specimen were molecular alterations found in the egfr mdm2 or tp53 genes the specimen obtained from the right hemisphere exhibited a high level of msi and loh in chromosome arms 5q 9p and 13q the specimen from the left hemisphere exhibited loh in chromosome arms 3p 5q 9p 9q 10p 10q and 13q here we propose four plausible hypothetical scenarios underlying the tumorigenesis of this gbm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17854667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1535, "text": "in humans high grade gliomas may infiltrate across the corpus callosum resulting in bihemispheric lesions that may have symmetrical winged like appearances this particular tumor manifestation has been coined a butterfly glioma bg while canine and human gliomas share many neuroradiological and pathological features the bg morphology has not been previously reported in dogs here we describe the magnetic resonance imaging mri characteristics of bg in three dogs and review the potential differential diagnoses based on neuroimaging findings all dogs presented for generalized seizures and interictal neurological deficits referable to multifocal or diffuse forebrain disease mri examinations revealed asymmetrical 2 3 or symmetrical 1 3 bihemispheric intra axial mass lesions that predominantly affected the frontoparietal lobes that were associated with extensive perilesional edema and involvement of the corpus callosum the masses displayed heterogeneous t1 t2 and fluid attenuated inversion recovery signal intensities variable contrast enhancement 2 3 and mass effect all tumors demonstrated classical histopathological features of glioblastoma multiforme gbm including glial cell pseudopalisading serpentine necrosis microvascular proliferation as well as invasion of the corpus callosum by neoplastic astrocytes although rare gbm should be considered a differential diagnosis in dogs with an mri evidence of asymmetric or symmetric bilateral intra axial cerebral mass lesions with signal characteristics compatible with glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458589", "endSection": "abstract" } ] }, { "body": "Which chromosomes are implicated in the Emanuel syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23691404", "http://www.ncbi.nlm.nih.gov/pubmed/18286821", "http://www.ncbi.nlm.nih.gov/pubmed/22434056", "http://www.ncbi.nlm.nih.gov/pubmed/24171835", "http://www.ncbi.nlm.nih.gov/pubmed/24980921", "http://www.ncbi.nlm.nih.gov/pubmed/23117075", "http://www.ncbi.nlm.nih.gov/pubmed/27973931", "http://www.ncbi.nlm.nih.gov/pubmed/26076791", "http://www.ncbi.nlm.nih.gov/pubmed/28981939", "http://www.ncbi.nlm.nih.gov/pubmed/21949351", "http://www.ncbi.nlm.nih.gov/pubmed/22876593", "http://www.ncbi.nlm.nih.gov/pubmed/19606488", "http://www.ncbi.nlm.nih.gov/pubmed/27617132", "http://www.ncbi.nlm.nih.gov/pubmed/28075445", "http://www.ncbi.nlm.nih.gov/pubmed/27785401" ], "ideal_answer": [ "Emanuel syndrome is associated with supernumerary chromosome t(11;22)(q23;q11), which consists of the extra genetic material from chromosomes 11 and 22." ], "exact_answer": [ [ "11" ], [ "22" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D002875", "http://amigo.geneontology.org/amigo/term/GO:0005694" ], "type": "list", "id": "5a736efc3b9d13c708000006", "snippets": [ { "offsetInBeginSection": 814, "offsetInEndSection": 1017, "text": "Single\u2011nucleotide polymorphism\u2011array analysis of the proband indicated a partial duplication of chromosomes 22 and 11 at 22q11.1\u2011q11.21 and 11q23.3\u2011q25, respectively, which confirmed the diagnosis of ES.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28075445", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 631, "text": "NGS and FISH analysis verified that the supernumerary marker chromosome carried by the fetus was der(22) t(11; 22) (q23;q11). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28981939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Emanuel syndrome is associated with supernumerary chromosome, which consists of the extra genetic material from chromosome 11 and 22. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27973931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Multiple congenital anomalies and craniofacial dysmorphism are characterizing the so-called Emanuel or supernumerary der(22)t(11;22) syndrome (OMIM609029).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26076791", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 288, "text": " Complex sSMCs consist of chromosomal material derived from more than one chromosome, for example, the derivative der(22)t(11;22)(q23;q11.2) in Emanuel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "A case with Emanuel syndrome: extra derivative 22 chromosome inherited from the mother.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27785401", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 263, "text": " Affected children are usually identified in the newborn period as the offspring of balanced (11;22) translocation carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27785401", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 603, "text": "We report a 3-year-old boy with the t(11;22)(q23;q11) chromosome, transmitted in an unbalanced fashion from his mother. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27785401", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 303, "text": "Balanced carriers of t(11;22) usually manifest no clinical symptoms, and are often identified after the birth of offspring with an unbalanced form of this translocation, known as Emanuel syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Derivative 11;22 (emanuel) syndrome: a case report and a review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23691404", "endSection": "title" }, { "offsetInBeginSection": 127, "offsetInEndSection": 326, "text": "Complex sSMC consist of chromosomal material derived from more than one chromosome; the best known representative of this group is the derivative chromosome 22 {der(22)t(11;22)} or Emanuel syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171835", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 221, "text": "The syndrome is caused by chromosomal imbalance due to a supernumerary derivative chromosome 22. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22434056", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1011, "text": "We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21949351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Emanuel syndrome is an inherited chromosomal abnormality resulting from 3:1 meiotic segregation from parental balanced translocation carrier t(11;22)(q23;q11), mostly of maternal origin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22876593", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 594, "text": "Here in, we describe a female patient with supernumerary der(22) syndrome (Emanuel syndrome) due to balanced translocation carrier father t(11;22) (q23;q11). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22876593", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 651, "text": "The t(11;22)(q23;q11.2) is the main recurrent germline translocation in humans. Unbalanced translocation can be transmitted to the progeny and can cause Emanuel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23117075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Complex small supernumerary marker chromosomes (sSMCs) constitute one of the smallest subsets within the patients with an sSMC. Complex sSMCs consist of chromosomal material derived from more than one chromosome, for example, the derivative der(22)t(11;22)(q23;q11.2) in Emanuel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Emanuel syndrome is associated with supernumerary chromosome, which consists of the extra genetic material from chromosome 11 and 22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27973931", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 526, "text": "The observed number of Emanuel syndrome cases was 36 and that of t(11;22) balanced translocation carriers, 40.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Emanuel syndrome is an inherited chromosomal abnormality resulting from 3:1 meiotic segregation from parental balanced translocation carrier t(11;22)(q23;q11), mostly of maternal origin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22876593", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Emanuel syndrome results from +der(22)t(11q23;22q11).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18286821", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 593, "text": "Here in, we describe a female patient with supernumerary der(22) syndrome (Emanuel syndrome) due to balanced translocation carrier father t(11;22) (q23;q11).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22876593", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 324, "text": "Complex sSMC consist of chromosomal material derived from more than one chromosome; the best known representative of this group is the derivative chromosome 22 {der(22)t(11;22)} or Emanuel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171835", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 288, "text": "Complex sSMCs consist of chromosomal material derived from more than one chromosome, for example, the derivative der(22)t(11;22)(q23;q11.2) in Emanuel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617132", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 302, "text": "Balanced carriers of t(11;22) usually manifest no clinical symptoms, and are often identified after the birth of offspring with an unbalanced form of this translocation, known as Emanuel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "supernumerary chromosome der 22 t 11 22 emanuel syndrome associates with novel features", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18286821", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "a case with emanuel syndrome extra derivative 22 chromosome inherited from the mother", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27785401", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1076, "text": "emanuel syndrome is a rare chromosomal disorder characterized by severe mental retardation and multiple anomalies the syndrome is caused by chromosomal imbalance due to a supernumerary derivative chromosome 22 little is known regarding the characteristics of prenatal biochemical screening or ultrasonographic markers in this syndrome we aimed to identify a prenatal screening pattern characteristic of emanuel syndrome we report the prenatal characteristics of five fetuses with emanuel syndrome four of which were diagnosed prenatally we found no consistent pattern of prenatal biochemical markers or other prenatal characteristics nevertheless increased nt low papp a and ultrasound features such as intra uterine growth restriction posterior fossa cardiac and bowel abnormalities may be helpful in raising the suspicion for this rare genetic syndrome review of the biochemical screening results ultrasound findings and demographic characteristics of this emanuel syndrome case series as well as of the relevant literature fail to suggest a characteristic prenatal pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22434056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 780, "text": "emanuel syndrome is associated with supernumerary chromosome which consists of the extra genetic material from chromosome 11 and 22 the frequency of this syndrome has been reported as 1 in 110 000 it is a rare anomaly associated with multiple systemic malformations such as micrognathia and congenital heart disease in addition patients with emanuel syndrome may have seizure disorders we experienced anesthetic management of a patient with emanuel syndrome who underwent palatoplasty this patient had received tracheotomy due to micrognathia in addition he had atrial septal defect mild pulmonary artery stenosis and cleft palate palatoplasty was performed without any complication during anesthesia close attention was directed to cardiac function seizure and airway management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27973931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1646, "text": "complex small supernumerary marker chromosomes ssmc constitute one of the smallest subgroups of ssmc in general complex ssmc consist of chromosomal material derived from more than one chromosome the best known representative of this group is the derivative chromosome 22 der 22 t 11 22 or emanuel syndrome in 2008 we speculated that complex ssmc could be part of an underestimated entity here the overall yet reported 412 complex ssmc are summarized they constitute 8 4 of all yet in detail characterized ssmc cases the majority of the complex ssmc is contributed by patients suffering from emanuel syndrome 82 besides there are a der 22 t 8 22 q24 1 q11 1 and a der 13 t 13 18 q11 p11 21 or der 21 t 18 21 p11 21 q11 1 der 13 or 21 t 13 or 21 18 syndrome the latter two represent another 2 6 and 2 2 of the complex ssmc cases respectively the large majority of complex ssmc has a centric minute shape and derives from an acrocentric chromosome nonetheless complex ssmc can involve material from each chromosomal origin most complex ssmc are inherited form a balanced translocation in one parent and are non mosaic interestingly there are hot spots for the chromosomal breakpoints involved complex ssmc need to be considered in diagnostics especially in non mosaic centric minute shaped ssmc as yet three complex ssmc associated syndromes are identified as recurrent breakpoints in the complex ssmc were characterized it is to be expected that more syndromes are identified in this subgroup of ssmc overall complex ssmc emphasize once more the importance of detailed cytogenetic analyses especially in patients with idiopathic mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1593, "text": "emanuel syndrome is characterized by multiple congenital anomalies and developmental disability it is caused by the presence of a supernumerary derivative chromosome that contains material from chromosomes 11 and 22 the origin of this imbalance is 3 1 malsegregation of a parental balanced translocation between chromosomes 11 and 22 which is the most common recurrent reciprocal translocation in humans little has been published on the clinical features of this syndrome since the 1980s and information on natural history is limited we designed a questionnaire to collect information from families recruited through an international online support group chromosome 22 central data gathered include information on congenital anomalies medical and surgical history developmental and behavioral issues and current abilities we received information on 63 individuals with emanuel syndrome ranging in age from newborn to adulthood as previously recognized congenital anomalies were common the most frequent being ear pits 76 micrognathia 60 heart malformations 57 and cleft palate 54 our data suggest that vision and hearing impairment seizures failure to thrive and recurrent infections particularly otitis media are common in this syndrome psychomotor development is uniformly delayed however the majority of individuals over 70 eventually learn to walk with support language development and ability for self care are also very impaired this study provides new information on the clinical spectrum and natural history of emanuel syndrome for families and physicians caring for these individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19606488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1393, "text": "emanuel syndrome is an inherited chromosomal abnormality resulting from 3 1 meiotic segregation from parental balanced translocation carrier t 11 22 q23 q11 mostly of maternal origin it is characterized by mental retardation microcephaly preauricular tag or sinus ear anomalies cleft or high arched palate micrognathia congenital heart diseases kidney abnormalities structural brain anomalies and genital anomalies in male here in we describe a female patient with supernumerary der 22 syndrome emanuel syndrome due to balanced translocation carrier father t 11 22 q23 q11 she was mentally and physically disabled and had most of the craniofacial dysmorphism of this syndrome our patient had cleft palate maldeveloped corpus callosum and hind brain with normal internal organs additionally arachnodactyly hyperextensibility of hand joints abnormal deep palmar and finger creases extra finger creases and bilateral talipus were evident and not previously described with this syndrome cytogenetic analysis and fish documented that the patient had both translocation chromosomes plus an additional copy of der 22 with karyotyping 47 xx t 11 22 q23 q11 der 22 t 11 22 q23 q11 we postulated that this rare chromosomal complement can arise from 2 2 segregation in the first meiotic division of the balanced translocation father followed by non disjunction at meiosis ii in the balanced spermatocyte.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22876593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 659, "text": "emanuel syndrome results from der 22 t 11q23 22q11 cleft palate ear anomalies heart defects genital anomalies hypotonia and mental retardation are the main features of the syndrome we report a nine year old boy with the t 11 22 q23 q11 chromosome transmitted in an unbalanced fashion from his mother and originated in the maternal grandmother s meiosis in addition to mental retardation hypotonia craniofacial anomalies and cryptorchidism he has novel findings such as joint hyperextensibility left liver lobe agenesis left sided malposition of the gallbladder and pancreas hypoplasia this is the first report associating these features with emanuel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18286821", "endSection": "abstract" } ] }, { "body": "Is a CpG island methylator phenotype involved in ependymomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22109108", "http://www.ncbi.nlm.nih.gov/pubmed/24553142", "http://www.ncbi.nlm.nih.gov/pubmed/25182241" ], "ideal_answer": [ "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype", "yes", "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death.", "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas. ", "Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype." ], "exact_answer": "yes", "type": "yesno", "id": "5a86fd5bfaa1ab7d2e00003b", "snippets": [ { "offsetInBeginSection": 444, "offsetInEndSection": 613, "text": "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553142", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 595, "text": "Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109108", "endSection": "title" }, { "offsetInBeginSection": 529, "offsetInEndSection": 739, "text": "Supratentorial and spinal tumors displayed significantly more hypermethylated genes than posterior fossa tumors, similar to the 'CpG island methylator phenotype' (CIMP) identified in glioma and colon carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109108", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1636, "text": "The data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal, but not posterior fossa ependymomas. Hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109108", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 614, "text": "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553142", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 988, "text": "CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553142", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 443, "text": "Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553142", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 594, "text": "Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1148, "text": "ependymomas are common childhood brain tumours that occur throughout the nervous system but are most common in the paediatric hindbrain current standard therapy comprises surgery and radiation but not cytotoxic chemotherapy as it does not further increase survival whole genome and whole exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate and zero significant recurrent somatic single nucleotide variants although devoid of recurrent single nucleotide variants and focal copy number aberrations poor prognosis hindbrain ependymomas exhibit a cpg island methylator phenotype transcriptional silencing driven by cpg methylation converges exclusively on targets of the polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of h3k27 cpg island methylator phenotype positive hindbrain ependymomas are responsive to clinical drugs that target either dna or h3k27 methylation both in vitro and in vivo we conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy which is epigenetically deregulated but genetically bland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109108", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "epigenomic alterations define lethal cimp positive ependymomas of infancy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553142", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "molecular genetics of ependymomas and pediatric diffuse gliomas a short review", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182241", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1613, "text": "epigenetic alterations including methylation have been shown to be an important mechanism of gene silencing in cancer ependymoma has been well characterized at the dna copy number and mrna expression levels however little is known about dna methylation changes to gain a more global view of the methylation profile of ependymoma we conducted an array based analysis our data demonstrated tumors to segregate according to their location in the cns which was associated with a difference in the global level of methylation supratentorial and spinal tumors displayed significantly more hypermethylated genes than posterior fossa tumors similar to the cpg island methylator phenotype cimp identified in glioma and colon carcinoma this hypermethylated profile was associated with an increase in expression of genes encoding for proteins involved in methylating dna suggesting an underlying mechanism an integrated analysis of methylation and mrna expression array data allowed us to identify methylation induced expression changes most notably genes involved in the control of cell growth and death and the immune system were identified including members of the jnk pathway and pparg in conclusion we have generated a global view of the methylation profile of ependymoma the data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal but not posterior fossa ependymomas hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22109108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1347, "text": "here we review the recent literature on molecular discoveries in ependymomas and pediatric diffuse gliomas ependymomas can now be categorized into three location related subgroups according to their biological profile posterior fossa ependymomas group a pfa and b pfb and supratentorial ependymomas although no recurrently mutated genes were found throughout these groups of ependymomas pfa exhibited a cpg island methylator phenotype pfb was associated with extensive chromosomal aberrations and the c11orf95 rela fusion gene was frequently observed in supratentorial ependymomas meanwhile it has now become apparent that pediatric diffuse gliomas have a distinct genetic status from their adult counterparts even though they share an indistinguishable histology in pediatric low grade diffuse gliomas an intragenic duplication of the portion of fgfr1 encoding the tyrosine kinase domain tkd and rearrangements of myb mybl1 were found recurrently and mutually exclusively as for non brainstem high grade tumors in addition to h3f3a tp53 and atrx mutations which were frequently observed in older children recurrent fusions involving ntrk1 ntrk2 and ntrk3 were reported in infants younger than 3 years of age moreover in diffuse intrinsic pontine gliomas dipg recurrent somatic mutations of acvr1 were found in association with hist1h3b mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182241", "endSection": "abstract" } ] }, { "body": "Are loop domains preserved upon cohesin loss?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28985562" ], "ideal_answer": [ "No. Degradation of cohesin leads to elimination of loop domains. Neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes." ], "exact_answer": "no", "type": "yesno", "id": "5a6e4814b750ff445500004a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Cohesin Loss Eliminates All Loop Domains.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28985562", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 637, "text": "The human genome folds to create thousands of intervals, called \"contact domains,\" that exhibit enhanced contact frequency within themselves. \"Loop domains\" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. \"Compartment domains\" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28985562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "cohesin loss eliminates all loop domains", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28985562", "endSection": "title" } ] }, { "body": "Which workflow in Bioconductor has been developed for accessing human RNA-seq samples?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29043067" ], "ideal_answer": [ "The recount2 resource is composed of over 70,000 uniformly processed human RNA-seq samples spanning TCGA and SRA, including GTEx." ], "exact_answer": [ "recount2" ], "type": "factoid", "id": "5a6e24a5b750ff445500003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "recount workflow: Accessing over 70,000 human RNA-seq samples with Bioconductor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29043067", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The recount2 resource is composed of over 70,000 uniformly processed human RNA-seq samples spanning TCGA and SRA, including GTEx.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29043067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "recount workflow accessing over 70 000 human rna seq samples with bioconductor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29043067", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 886, "text": "the recount2 resource is composed of over 70 000 uniformly processed human rna seq samples spanning tcga and sra including gtex the processed data can be accessed via the recount2 website and the bioconductor package this workflow explains in detail how to use the package and how to integrate it with other bioconductor packages for several analyses that can be carried out with the recount2 resource in particular we describe how the coverage count matrices were computed in recount2 as well as different ways of obtaining public metadata which can facilitate downstream analyses step by step directions show how to do a gene level differential expression analysis visualize base level genome coverage data and perform an analyses at multiple feature levels this workflow thus provides further information to understand the data in recount2 and a compendium of r code to use the data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29043067", "endSection": "abstract" } ] }, { "body": "What does VBP15 do to skeletal muscle?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24014378" ], "ideal_answer": [ "VBP15 protects and promotes efficient repair of skeletal muscle cells. Potent inhibition of NF-\u03baB is mediated through protein interactions of the glucocorticoid receptor, however VBP15 shows significantly reduced hormonal receptor transcriptional activity. In DMD model mice it improves muscle strength, live-imaging and pathology through both preventive and post-onset intervention regimens." ], "type": "summary", "id": "5a76dd749e632bc066000008", "snippets": [ { "offsetInBeginSection": 617, "offsetInEndSection": 1338, "text": "We find VBP15 protects and promotes efficient repair of skeletal muscle cells upon laser injury, in opposition to prednisolone. Potent inhibition of NF-\u03baB is mediated through protein interactions of the glucocorticoid receptor, however VBP15 shows significantly reduced hormonal receptor transcriptional activity. The translation of these drug mechanisms into DMD model mice improves muscle strength, live-imaging and pathology through both preventive and post-onset intervention regimens. These data demonstrate successful improvement of dystrophy independent of hormonal, growth, or immunosuppressive effects, indicating VBP15 merits clinical investigation for DMD and would benefit other chronic inflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24014378", "endSection": "abstract" } ] }, { "body": "What is filgotinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27988142", "http://www.ncbi.nlm.nih.gov/pubmed/27993828" ], "ideal_answer": [ "Filgotinib is an oral selective Janus kinase inhibitor. It has been tested in patients with rheumatoid arthritis and Chroni's disease, and has been shown to be safe and efficacious." ], "type": "summary", "id": "5a760a4183b0d9ea66000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993828", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 235, "text": "To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993828", "endSection": "abstract" }, { "offsetInBeginSection": 1650, "offsetInEndSection": 1785, "text": "Over 24\u2005weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993828", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 245, "text": "Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohn's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27988142", "endSection": "abstract" }, { "offsetInBeginSection": 1884, "offsetInEndSection": 2374, "text": "In the intention-to-treat population, 60 (47%) of 128 patients treated with filgotinib 200 mg achieved clinical remission at week 10 versus ten (23%) of 44 patients treated with placebo (difference 24 percentage points [95% CI 9-39], p=0\u00b70077). In a pooled analysis of all periods of filgotinib and placebo exposure over 20 weeks, serious treatment-emergent adverse effects were reported in 14 (9%) of 152 patients treated with filgotinib and three (4%) of 67 patients treated with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27988142", "endSection": "abstract" }, { "offsetInBeginSection": 2390, "offsetInEndSection": 2547, "text": "Filgotinib induced clinical remission in significantly more patients with active Crohn's disease compared with placebo, and had an acceptable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27988142", "endSection": "abstract" } ] }, { "body": "What is Q-nexus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27814676" ], "ideal_answer": [ "Q-nexus is a comprehensive and efficient analysis pipeline designed for ChIP-nexus." ], "type": "summary", "id": "5a6e1db0b750ff4455000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Q-nexus: a comprehensive and efficient analysis pipeline designed for ChIP-nexus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27814676", "endSection": "title" } ] }, { "body": "What is the mechanism of action of Tisagenlecleucel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29039115", "http://www.ncbi.nlm.nih.gov/pubmed/28887358", "http://www.ncbi.nlm.nih.gov/pubmed/28751490", "http://www.ncbi.nlm.nih.gov/pubmed/28935694", "http://www.ncbi.nlm.nih.gov/pubmed/29058636", "http://www.ncbi.nlm.nih.gov/pubmed/29143249" ], "ideal_answer": [ "Tisagenlecleucel CD19-directed chimeric antigen receptor T cells (CART19) product that cause reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. Its is is approved for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia." ], "type": "summary", "id": "5a75df9483b0d9ea66000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "An expert panel recommended approval of Novartis's experimental chimeric antigen T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28751490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28935694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "The first chimeric antigen receptor T-cell therapy, tisagenlecleucel, received FDA approval for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia who haven't responded to standard therapy or who have relapsed at least twice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887358", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 300, "text": "Chimeric antigen receptor (CAR)-engineered T cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058636", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 737, "text": "Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have led to impressive responses in patients with B-cell leukemia and lymphoma. CTL019, or KYMRIAH\u2122 (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29039115", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 478, "text": "Indeed, on August 30, 2017, the University of Pennsylvania-designed CD19-directed CART (CART-19) cell therapy (CTL019, tisagenlecleucel-t, Kymriah - Novartis) became the first CART therapy approved by the Food and Drug Administration (FDA) for acute lymphoblastic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28935694", "endSection": "title" }, { "offsetInBeginSection": 201, "offsetInEndSection": 299, "text": "CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058636", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 737, "text": "CTL019, or KYMRIAH\u2122 (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29039115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "An expert panel recommended approval of Novartis's experimental chimeric antigen T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28751490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "an expert panel recommended approval of novartis s experimental chimeric antigen t cell therapy tisagenlecleucel for children and young adults with relapsed or refractory b cell acute lymphoblastic leukemia the therapy would be the first of its kind approved for cancer and has the potential to transform standard of care for advanced blood cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28751490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 921, "text": "novel immunotherapeutic agents targeting tumor site microenvironment are revolutionizing cancer therapy chimeric antigen receptor car engineered t cells are widely studied for cancer immunotherapy cd19 specific car t cells tisagenlecleucel have been recently approved for clinical application ongoing clinical trials are testing car designs directed at novel targets involved in hematological and solid malignancies in addition to trials of single target car t cells simultaneous and sequential car t cells are being studied for clinical applications multi target car engineered t cells are also entering clinical trials t cell receptor engineered car t and universal car t cells represent new frontiers in car t cell development in this study we analyzed the characteristics of car constructs and registered clinical trials of car t cells in china and provided a quick glimpse of the landscape of car t studies in china.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1006, "text": "in this review we discuss the most recent developments in gene editing technology and discuss their application to adoptive t cell immunotherapy engineered t cell therapies targeting cancer antigens have demonstrated significant efficacy in specific patient populations most impressively cd19 directed chimeric antigen receptor t cells cart19 have led to impressive responses in patients with b cell leukemia and lymphoma ctl019 or kymriah tisagenlecleucel a cd19 car t cell product developed by novartis and the university of pennsylvania was recently approved for clinical use by the food and drug administration representing a landmark in the application of adoptive t cell therapies as cart19 enters routine clinical use improving the efficacy of this exciting platform is the next step in broader application novel gene editing technologies like crispr cas9 allow facile editing of specific genes within the genome generating a powerful platform to further optimize the activity of engineered t cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29039115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1163, "text": "autologous patient specific chimeric antigen receptor t cell cart therapy has emerged as a powerful and potentially curative therapy for cancer especially for cd19 positive hematological malignancies indeed on august 30 2017 the university of pennsylvania designed cd19 directed cart cart 19 cell therapy ctl019 tisagenlecleucel t kymriah novartis became the first cart therapy approved by the food and drug administration fda for acute lymphoblastic leukemia however the development of cart technology and its wider application is partly limited by the patient specific nature of such a platform and by the time required for manufacturing the efficacious generation of universal allogeneic cart cells would overcome these limitations and represent a major advance in the field however several obstacles in the generation of universal cart cells need to be overcome namely the risk of cart rejection and the risk of graft versus host disease mediated by the allogeneic cart in this review we discuss the different strategies being employed to generate universal cart and provide our perspective on the successful development of a truly off the shelf cart product.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143249", "endSection": "abstract" } ] }, { "body": "What is LHON, also known as Lebers syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7916404", "http://www.ncbi.nlm.nih.gov/pubmed/9010406", "http://www.ncbi.nlm.nih.gov/pubmed/21174521", "http://www.ncbi.nlm.nih.gov/pubmed/10993496", "http://www.ncbi.nlm.nih.gov/pubmed/27843288", "http://www.ncbi.nlm.nih.gov/pubmed/26894521", "http://www.ncbi.nlm.nih.gov/pubmed/26218905", "http://www.ncbi.nlm.nih.gov/pubmed/9147893", "http://www.ncbi.nlm.nih.gov/pubmed/17406640", "http://www.ncbi.nlm.nih.gov/pubmed/27613247", "http://www.ncbi.nlm.nih.gov/pubmed/9177303", "http://www.ncbi.nlm.nih.gov/pubmed/21346843", "http://www.ncbi.nlm.nih.gov/pubmed/22390282", "http://www.ncbi.nlm.nih.gov/pubmed/20809775", "http://www.ncbi.nlm.nih.gov/pubmed/24167936", "http://www.ncbi.nlm.nih.gov/pubmed/7999980", "http://www.ncbi.nlm.nih.gov/pubmed/11906302", "http://www.ncbi.nlm.nih.gov/pubmed/26448041", "http://www.ncbi.nlm.nih.gov/pubmed/9309689", "http://www.ncbi.nlm.nih.gov/pubmed/27756254", "http://www.ncbi.nlm.nih.gov/pubmed/28991104", "http://www.ncbi.nlm.nih.gov/pubmed/20632027", "http://www.ncbi.nlm.nih.gov/pubmed/16523300", "http://www.ncbi.nlm.nih.gov/pubmed/11329546", "http://www.ncbi.nlm.nih.gov/pubmed/12031765", "http://www.ncbi.nlm.nih.gov/pubmed/23113023", "http://www.ncbi.nlm.nih.gov/pubmed/10758737", "http://www.ncbi.nlm.nih.gov/pubmed/1449769", "http://www.ncbi.nlm.nih.gov/pubmed/21694444", "http://www.ncbi.nlm.nih.gov/pubmed/21734595", "http://www.ncbi.nlm.nih.gov/pubmed/8605641" ], "ideal_answer": [ "Leber's hereditary optic neuropathy (LHON) is a common inherited mitochondrial disorder that is characterized by the degeneration of the optic nerves, leading to vision loss." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:705", "https://meshb.nlm.nih.gov/record/ui?ui=D029242" ], "type": "summary", "id": "5a74d9980384be9551000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 808, "text": "Mitochondrial diseases are a clinically hetyerogenous group of disorders. They can be caused by mutations of nuclear or mitochondrial DNA (mtDNA). Some affect a single organ, but many involve multiple organ systems and often present with prominent neurologic and myopathic features. The eye is frequently affected, along with muscles and brain, but multisystem disease is common. Ophthalmic manifestations include cataract, retinopathy, optic atrophy, cortical visual loss, ptosis and ophthalmoplegia. Kearns-Sayre Syndrome (KSS), Mitochondrial Encephalopathy, Lactic Acidosis Stroke (MELAS), Myoclonic Epilepsy and Ragged Red Fiber myopathy (MERRF) and Lebers Hereditary Optic Neuropathy (LHON) are well known clinical entities that are secondary to mtDNA abnormalities, which has ophthalmic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21346843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Genetic counseling in Leber hereditary optic neuropathy (LHON).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11906302", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "To demonstrate the importance of mitochondrial DNA (mtDNA) analysis in the diagnosis of Leber hereditary optic neuropathy (LHON) and illustrate the difficulties in genetic counseling of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11906302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "To discuss recent advances in potential treatments for Leber hereditary optic neuropathy (LHON), a typically visually devastating hereditary optic neuropathy caused by mutations in the mitochondrial genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26448041", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 808, "text": "Kearns-Sayre Syndrome (KSS), Mitochondrial Encephalopathy, Lactic Acidosis Stroke (MELAS), Myoclonic Epilepsy and Ragged Red Fiber myopathy (MERRF) and Lebers Hereditary Optic Neuropathy (LHON) are well known clinical entities that are secondary to mtDNA abnormalities, which has ophthalmic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21346843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder with bilateral loss of central vision primarily due to mitochondrial DNA (mtDNA) mutations in subunits of complex I in the respiratory chain (primary LHON mutations), while other mtDNA mutations can also be causative.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27843288", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 508, "text": "The phenotypic characteristics of the syndrome resemble those found in other mitochondrial (mt)DNA mediated disorders such as Leber's hereditary optic neuropathy (LHON) or maternally inherited diabetes and deafness (MIDD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9309689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16523300", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease characterized by bilateral acute or subacute progressive central visual loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27613247", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 262, "text": "Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22390282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "BACKGROUND Leber's hereditary optic neuropathy (LHON) co-occuring with multiple sclerosis-like disease (LHON-MS) is suggested to be a separate disease entity denoted Harding's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756254", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 141, "text": "To investigate the prevalence and spectrum of mitochondrial ND4 mutations in subjects with Leber's hereditary optic neuropathy (LHON", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26218905", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 106, "text": "Three mitochondrial mutations account for 95% of Leber's hereditary optic neuropathy (LHON) in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20809775", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 95, "text": "Leber hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, myopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26894521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21694444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by bilateral painless optic atrophy and blindness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20632027", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 139, "text": "Leber hereditary optic neuropathy (LHON) is an inherited form of bilateral optic atrophy leading to the loss of central vision.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23113023", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 587, "text": "3 Leber's hereditary optic neuropathy (LHON),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8605641", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 156, "text": " Leber's hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21174521", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 794, "text": "LHON (Leber's Hereditary Optic Neuropathy)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7999980", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 71, "text": "eber's hereditary optic neuropathy (LHON) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10993496", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 166, "text": "Leber's hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12031765", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 166, "text": "Leber's hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11329546", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 111, "text": "Leber's hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9147893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Lebers hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24167936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Leber hereditary optic neuropathy (LHON) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28991104", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 225, "text": "Lebers hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9177303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Leber hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1449769", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 130, "text": " Leber hereditary optic neuropathy (LHON)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17406640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Leber hereditary optic neuropathy (LHON) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21734595", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 302, "text": "Leber hereditary optic neuropathy (LHON) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9010406", "endSection": "abstract" } ] }, { "body": "What is the ReliableGenome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27605105" ], "ideal_answer": [ "The increasing adoption of clinical whole-genome resequencing (WGS) demands for highly accurate and reproducible variant calling (VC) methods. The observed discordance between state-of-the-art VC pipelines, however, indicates that the current practice still suffers from non-negligible numbers of false positive and negative SNV and INDEL calls that were shown to be enriched among discordant calls but also in genomic regions with low sequence complexity. ReliableGenome is a method for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines. It combines call sets derived by multiple pipelines from arbitrary numbers of datasets and interpolates expected concordance for genomic regions without data." ], "type": "summary", "id": "5a761ac7aacfb9cd4c000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "ReliableGenome: annotation of genomic regions with high/low variant calling concordance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1196, "text": "The increasing adoption of clinical whole-genome resequencing (WGS) demands for highly accurate and reproducible variant calling (VC) methods. The observed discordance between state-of-the-art VC pipelines, however, indicates that the current practice still suffers from non-negligible numbers of false positive and negative SNV and INDEL calls that were shown to be enriched among discordant calls but also in genomic regions with low sequence complexity.RESULTS: Here, we describe our method ReliableGenome (RG) for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines. Our method combines call sets derived by multiple pipelines from arbitrary numbers of datasets and interpolates expected concordance for genomic regions without data. By applying RG to 219 deep human WGS datasets, we demonstrate that VC concordance depends predominantly on genomic context rather than the actual sequencing data which manifests in high recurrence of regions that can/cannot be reliably genotyped by a single method. This enables the application of pre-computed regions to other data created with comparable sequencing technology and software.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 616, "text": "Here, we describe our method ReliableGenome (RG) for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 654, "text": "The observed discordance between state-of-the-art VC pipelines, however, indicates that the current practice still suffers from non-negligible numbers of false positive and negative SNV and INDEL calls that were shown to be enriched among discordant calls but also in genomic regions with low sequence complexity.
RESULTS: Here, we describe our method ReliableGenome (RG) for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 637, "text": "Here, we describe our method ReliableGenome (RG) for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 637, "text": "RESULTS Here, we describe our method ReliableGenome (RG) for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "reliablegenome annotation of genomic regions with high low variant calling concordance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2015, "text": "the increasing adoption of clinical whole genome resequencing wgs demands for highly accurate and reproducible variant calling vc methods the observed discordance between state of the art vc pipelines however indicates that the current practice still suffers from non negligible numbers of false positive and negative snv and indel calls that were shown to be enriched among discordant calls but also in genomic regions with low sequence complexity here we describe our method reliablegenome rg for partitioning genomes into high and low concordance regions with respect to a set of surveyed vc pipelines our method combines call sets derived by multiple pipelines from arbitrary numbers of datasets and interpolates expected concordance for genomic regions without data by applying rg to 219 deep human wgs datasets we demonstrate that vc concordance depends predominantly on genomic context rather than the actual sequencing data which manifests in high recurrence of regions that can cannot be reliably genotyped by a single method this enables the application of pre computed regions to other data created with comparable sequencing technology and software rg outperforms comparable efforts in predicting vc concordance and false positive calls in low concordance regions which underlines its usefulness for variant filtering annotation and prioritization rg allows focusing resource intensive algorithms e g consensus calling methods on the smaller discordant share of the genome 20 30 which might result in increased overall accuracy at reasonable costs our method and analysis of discordant calls may further be useful for development benchmarking and optimization of vc algorithms and for the relative comparison of call sets between different studies pipelines rg was implemented in java source code and binaries are freely available for non commercial use at https github com popitsch wtchg rg contact niko wtchg ox ac uksupplementary information supplementary data are available at bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605105", "endSection": "abstract" } ] }, { "body": "List polyubiquitin binding proteins involved in NF-kappaB signaling.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23509369", "http://www.ncbi.nlm.nih.gov/pubmed/18995839", "http://www.ncbi.nlm.nih.gov/pubmed/19285159", "http://www.ncbi.nlm.nih.gov/pubmed/23989959" ], "ideal_answer": [ "NEMO\nA20\nABIN-1\nABIN-2\noptineurin\np62" ], "exact_answer": [ [ "NEMO" ], [ "A20" ], [ "ABIN-1" ], [ "ABIN-2" ], [ "optineurin" ], [ "p62" ] ], "type": "list", "id": "5a8a9abdfcd1d6a10c000019", "snippets": [ { "offsetInBeginSection": 170, "offsetInEndSection": 438, "text": "he discovery that NEMO is a polyubiquitin-binding protein and that the IKK complex is modulated by other protein kinases that are themselves controlled by polyubiquitin chains has provided a deeper molecular understanding of the non-degradative roles of ubiquitylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23989959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Essential roles of K63-linked polyubiquitin-binding proteins TAB2 and TAB3 in B cell activation via MAPKs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23509369", "endSection": "title" }, { "offsetInBeginSection": 559, "offsetInEndSection": 792, "text": "Novel polyubiquitin binders AWP1, CALCOCO2, N4BP1, RIO3, TEX27, TTC3, UBFD1 and ZNF313 were identified using this approach, while known NF-kappaB regulators including NEMO, A20, ABIN-1, ABIN-2, optineurin and p62 were also identified", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19285159", "endSection": "abstract" } ] }, { "body": "What are the prednisone side effects in DMD patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12548530" ], "ideal_answer": [ "Side effects of prednisone in DMD patients include reduced growth rate and increase in body weight." ], "exact_answer": [ [ "Reduced growth rate" ], [ "Increase in weight", "weight gain" ] ], "type": "list", "id": "5a7723b79e632bc06600000b", "snippets": [ { "offsetInBeginSection": 567, "offsetInEndSection": 718, "text": " Side effects included a decline in growth rate in the prednisone-treated patients and excessive weight gain in one control and three treated patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12548530", "endSection": "abstract" } ] }, { "body": "Which is the specificity of deubiquitinase USP25?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24260525", "http://www.ncbi.nlm.nih.gov/pubmed/28327663", "http://www.ncbi.nlm.nih.gov/pubmed/23754700" ], "ideal_answer": [ "Ubiquitin Specific Protease 25 (USP25), a member of the deubiquitinase family, is involved in several disease-related signal pathways including myogenesis, immunity and protein degradation. It specially catalyzes the hydrolysis of the K48-linked and K63-linked polyubiquitin chains." ], "type": "summary", "id": "5a8aa253fcd1d6a10c00001b", "snippets": [ { "offsetInBeginSection": 258, "offsetInEndSection": 312, "text": "Here we show that the tandem UIM region binds to Lys48", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28327663", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 893, "text": "In addition, detailed analysis demonstrated that USP25 cleaved lysine 48- and lysine 63-linked polyubiquitin chains in vitro and in vivo, and its deubiquitinating enzyme (DUB) activity, were dependent on a cysteine residue (Cys178) and a histidine residue (His607)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Ubiquitin Specific Protease 25 (USP25), a member of the deubiquitinase family, is involved in several disease-related signal pathways including myogenesis, immunity and protein degradation. It specially catalyzes the hydrolysis of the K48-linked and K63-linked polyubiquitin chains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754700", "endSection": "abstract" } ] }, { "body": "Is Loss of function one of the cardinal signs of inflammation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12776909", "http://www.ncbi.nlm.nih.gov/pubmed/28282278", "http://www.ncbi.nlm.nih.gov/pubmed/29135930", "http://www.ncbi.nlm.nih.gov/pubmed/12799851" ], "ideal_answer": [ "Functio Laesa also known as loss of function is considered to be the 5th cardinal sign of inflammation." ], "exact_answer": "yes", "type": "yesno", "id": "5a7a44b4faa1ab7d2e000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The concept of the four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, (redness and swelling with heat and pain) extended later by functio laesa (loss of function).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12776909", "endSection": "abstract" }, { "offsetInBeginSection": 60, "offsetInEndSection": 255, "text": "As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response-redness, heat, swelling and pain; a fifth sign is loss of function.[...", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29135930", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1195, "text": "It was Galen who added the disturbance of function (functio laesa) as the fifth cardinal sign of inflammation to the four well-known cardinal signs of Celsus (rubor, calor, tumor, dolor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12799851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. The fifth-functio laesa, or loss of function-was promulgated by Rudolf Virchow, who, in the 19th century, also noted an intricate link between inflammation and cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28282278", "endSection": "abstract" } ] }, { "body": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26321255" ], "ideal_answer": [ "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.", "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.", "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains . Parp1- and ctcf-regulated contacts between circadian loci to the lamina, followed by the acquisition of repressive h3k9me2 marks and transcriptional attenuation here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains . PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. ", "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains . PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. ", "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. ", "yes", "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. Here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains. ", "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D002940", "http://amigo.geneontology.org/amigo/term/GO:0007623", "http://www.uniprot.org/uniprot/CTCF_MOUSE", "http://www.uniprot.org/uniprot/CTCF_CHICK", "https://meshb.nlm.nih.gov/record/ui?ui=D000067856", "https://meshb.nlm.nih.gov/record/ui?ui=D011065", "https://meshb.nlm.nih.gov/record/ui?ui=D011064", "https://meshb.nlm.nih.gov/record/ui?ui=D000071137", "https://meshb.nlm.nih.gov/record/ui?ui=D039103", "http://amigo.geneontology.org/amigo/term/GO:0072572", "https://meshb.nlm.nih.gov/record/ui?ui=D039102", "https://meshb.nlm.nih.gov/record/ui?ui=D000075223", "http://amigo.geneontology.org/amigo/term/GO:0042753", "http://amigo.geneontology.org/amigo/term/GO:0042754", "http://amigo.geneontology.org/amigo/term/GO:0048512", "http://www.uniprot.org/uniprot/CTCF_RAT", "https://meshb.nlm.nih.gov/record/ui?ui=D000075225", "http://www.uniprot.org/uniprot/CTCF_HUMAN", "http://amigo.geneontology.org/amigo/term/GO:0009649", "https://meshb.nlm.nih.gov/record/ui?ui=D020178", "https://meshb.nlm.nih.gov/record/ui?ui=D056925" ], "type": "yesno", "id": "5a86e66dfaa1ab7d2e000035", "snippets": [ { "offsetInBeginSection": 162, "offsetInEndSection": 306, "text": "here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26321255", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 759, "text": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26321255", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1127, "text": "PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26321255", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 1127, "text": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26321255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1112, "text": "transcriptionally active and inactive chromatin domains tend to segregate into separate sub nuclear compartments to maintain stable expression patterns however here we uncovered an inter chromosomal network connecting active loci enriched in circadian genes to repressed lamina associated domains lads the interactome is regulated by parp1 and its co factor ctcf they not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina synchronization of the circadian rhythm by serum shock induces oscillations in parp1 ctcf interactions which is accompanied by oscillating recruitment of circadian loci to the lamina followed by the acquisition of repressive h3k9me2 marks and transcriptional attenuation furthermore depletion of h3k9me2 3 inhibition of parp activity by olaparib or downregulation of parp1 or ctcf expression counteracts both recruitment to the envelope and circadian transcription parp1 and ctcf regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26321255", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 760, "text": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26321255", "endSection": "abstract" } ] }, { "body": "What induces Arabidopsis ROF1 expression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23133621", "http://www.ncbi.nlm.nih.gov/pubmed/19366428", "http://www.ncbi.nlm.nih.gov/pubmed/14996219", "http://www.ncbi.nlm.nih.gov/pubmed/17080288", "http://www.ncbi.nlm.nih.gov/pubmed/8914512" ], "ideal_answer": [ "The abundance of ROF1 increased several-fold under stress conditions such as wounding, heat stress or exposure to elevated NaCl levels." ], "exact_answer": [ [ "Wounding" ], [ "Elevated NaCl levels" ], [ "Heat" ] ], "type": "list", "id": "5a888b56d543831129000002", "snippets": [ { "offsetInBeginSection": 833, "offsetInEndSection": 1056, "text": "Endogenous ROF1 was shown to accumulate in response to high salt treatment in Arabidopsis thaliana young leaves as well as in seedlings germinated on high salt media (0.15 and 0.2 M NaCl) at both an mRNA and protein level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Arabidopsis ROF1 (AtFKBP62) is a peptidyl prolyl cis/trans isomerase and a member of the FKBP (FK506 binding protein) family. ROF1 expression is induced by heat stress and developmentally regulated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19366428", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 852, "text": "Exposure of plants to low levels of MDA using a recently developed protocol powerfully upregulated many genes on a cDNA microarray with a bias towards those implicated in abiotic/environmental stress (e.g. ROF1 and XERO2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14996219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Arabidopsis immunophilins ROF1 (AtFKBP62) and ROF2 (AtFKBP65) exhibit tissue specificity, are heat-stress induced, and bind HSP90.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17080288", "endSection": "title" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1064, "text": "The abundance of ROF1 mRNA increased several-fold under stress conditions such as wounding or exposure to elevated NaCl levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8914512", "endSection": "abstract" } ] }, { "body": "What is the preferred orientation of CTCF binding sites for chromatin looping?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26276636", "http://www.ncbi.nlm.nih.gov/pubmed/26499245", "http://www.ncbi.nlm.nih.gov/pubmed/26527277", "http://www.ncbi.nlm.nih.gov/pubmed/27940490", "http://www.ncbi.nlm.nih.gov/pubmed/28536180", "http://www.ncbi.nlm.nih.gov/pubmed/25497547" ], "ideal_answer": [ "chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs \"facing\" one another.", "As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner. Recent studies identified a correlation between the orientation of CTCF-binding sites and chromatin loops. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. ", "As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function." ], "exact_answer": [ "convergent", "Convergent orientation" ], "type": "factoid", "id": "5a895f51fcd1d6a10c000004", "snippets": [ { "offsetInBeginSection": 126, "offsetInEndSection": 236, "text": "Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28536180", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 904, "text": "Conversely, CTCF binding sites in NPCs are largely preexisting in pluripotent stem cells. Only a small number of CTCF sites arise de novo in NPCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28536180", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1406, "text": " Moreover, siRNA knockdown ofYy1specifically disrupts interactions between key NPC enhancers and their target genes. YY1-mediated interactions between NPC regulatory elements are often nested within constitutive loops anchored by CTCF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28536180", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 392, "text": "As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527277", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 697, "text": "In all instances, CTCF and cohesin recruitment were lost, and chromatin loops with distal, convergent CTCF sites were disrupted or destabilized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527277", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 841, "text": "Re-insertion of oppositely oriented CTCF recognition sequences restored CTCF and cohesin recruitment, but did not re-establish chromatin loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527277", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 257, "text": "Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26276636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26276636", "endSection": "title" }, { "offsetInBeginSection": 635, "offsetInEndSection": 767, "text": "CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs \"facing\" one another. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25497547", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 393, "text": "As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 940, "text": "ccctc binding factor ctcf is an architectural protein involved in the three dimensional 3d organization of chromatin in this study we assayed the 3d genomic contact profiles of a large number of ctcf binding sites with high resolution 4c seq as recently reported our data also suggest that chromatin loops preferentially form between ctcf binding sites oriented in a convergent manner to directly test this we used crispr cas9 genome editing to delete core ctcf binding sites in three loci including the ctcf site in the sox2 super enhancer in all instances ctcf and cohesin recruitment were lost and chromatin loops with distal convergent ctcf sites were disrupted or destabilized re insertion of oppositely oriented ctcf recognition sequences restored ctcf and cohesin recruitment but did not re establish chromatin loops we conclude that ctcf binding polarity plays a functional role in the formation of higher order chromatin structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26527277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1605, "text": "we recently used in situ hi c to create kilobase resolution 3d maps of mammalian genomes here we combine these maps with new hi c microscopy and genome editing experiments to study the physical structure of chromatin fibers domains and loops we find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer combining hi c data and novel mathematical theorems we show that contact domains are also not consistent with a fractal globule instead we use physical simulations to study two models of genome folding in one intermonomer attraction during polymer condensation leads to formation of an anisotropic tension globule in the other ccctc binding factor ctcf and cohesin act together to extrude unknotted loops during interphase both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops however the extrusion model explains a far wider array of observations such as why loops tend not to overlap and why the ctcf binding motifs at pairs of loop anchors lie in the convergent orientation finally we perform 13 genome editing experiments examining the effect of altering ctcf binding sites on chromatin folding the convergent rule correctly predicts the affected loops in every case moreover the extrusion model accurately predicts in silico the 3d maps resulting from each experiment using only the location of ctcf binding sites in the wt thus we show that it is possible to disrupt restore and move loops and domains using targeted mutations as small as a single base pair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26499245", "endSection": "abstract" } ] }, { "body": "Does erythromycin increase risk of hypertrophic pyloric stenosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27655365", "http://www.ncbi.nlm.nih.gov/pubmed/12100810", "http://www.ncbi.nlm.nih.gov/pubmed/12693559", "http://www.ncbi.nlm.nih.gov/pubmed/11562617", "http://www.ncbi.nlm.nih.gov/pubmed/25687145", "http://www.ncbi.nlm.nih.gov/pubmed/23558266" ], "ideal_answer": [ "Yes, post-natal erythromycin exposure is associated with increased risk of hypertrophic pyloric stenosis. The association is stronger when exposure occurs in the first 2 weeks of life." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D046248", "https://meshb.nlm.nih.gov/record/ui?ui=D012306", "https://meshb.nlm.nih.gov/record/ui?ui=D004917" ], "type": "yesno", "id": "5a67ade5b750ff445500000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655365", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "PURPOSE: Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655365", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 932, "text": " Overall, erythromycin exposure was significantly associated with development of IHPS [OR 2.45 (1.12-5.35), p\u00a0=\u00a00.02]. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655365", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1443, "text": "Data on erythromycin exposure in the first 14\u00a0days of life was extracted from 4/9 studies and identified a strong association between erythromycin exposure and subsequent development IHPS [OR 12.89 (7.67-2167), p\u00a0<\u00a00.00001].CONCLUSION: This study demonstrates a significant association between post-natal erythromycin exposure and development of IHPS, which seems stronger when exposure occurs in the first 2\u00a0weeks of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND AND OBJECTIVE: Use of oral erythromycin in infants is associated with infantile hypertrophic pyloric stenosis (IHPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687145", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1385, "text": "CONCLUSIONS: Ingestion of oral azithromycin and erythromycin places young infants at increased risk of developing IHPS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687145", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1188, "text": "An association between erythromycin and IHPS was also confirmed. Exposure to erythromycin in the first 14 days of life had an aOR of 13.3 (95% CI, 6.80-25.9), and 15 to 42 days of life, aOR 4.10 (95% CI, 1.69-9.91). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 406, "text": "Early exposure to oral erythromycin in young infants, particularly in the first 2 weeks of life, has previously been associated with the development of hypertrophic pyloric stenosis. We report a case of an infant who received an abbreviated 4-day course of oral erythromycin for suspected Chlamydia conjunctivitis at 5 days of life then underwent pyloromyotomy for pyloric stenosis less than 2 weeks later.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23558266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11562617", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "A case report has suggested that exposure to erythromycin through breast milk might cause infantile hypertrophic pyloric stenosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12693559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655365", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 622, "text": "Infants prescribed systemic erythromycin had increased risk of IHPS, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11562617", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1476, "text": "There was an association between maternal prescriptions for nonerythromycin macrolides and infantile hypertrophic pyloric stenosis (adjusted odds ratio 2.77, 95% confidence interval 1.22, 6.30, P =.01).
CONCLUSION: The hypothesized association between erythromycin and infantile pyloric stenosis was not seen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12100810", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 147, "text": "Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655365", "endSection": "abstract" } ] }, { "body": "How many amino acids does davunetide consist of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25505609" ], "ideal_answer": [ "Davunetide or NAP is an eight amino acid peptide." ], "exact_answer": [ "eight" ], "type": "factoid", "id": "5a7d4e9afaa1ab7d2e000013", "snippets": [ { "offsetInBeginSection": 370, "offsetInEndSection": 600, "text": "We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human \u03b1-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25505609", "endSection": "abstract" } ] }, { "body": "Can a circRNA be translated into protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "http://www.ncbi.nlm.nih.gov/pubmed/27617908", "http://www.ncbi.nlm.nih.gov/pubmed/27255916", "http://www.ncbi.nlm.nih.gov/pubmed/26649774", "http://www.ncbi.nlm.nih.gov/pubmed/27612318", "http://www.ncbi.nlm.nih.gov/pubmed/29028266", "http://www.ncbi.nlm.nih.gov/pubmed/26874353", "http://www.ncbi.nlm.nih.gov/pubmed/28344082", "http://www.ncbi.nlm.nih.gov/pubmed/28344080", "http://www.ncbi.nlm.nih.gov/pubmed/27892769" ], "ideal_answer": [ "Circ-ZNF609 is associated with heavy polysomes, and it is translated into a protein in a splicing-dependent and cap-independent manner, providing an example of a protein-coding circRNA in eukaryotes.\nCircular RNAs (circRNAs) represent a large class of noncoding RNAs (ncRNAs) that have recently emerged as regulators of gene expression\t\nHowever, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported", "\u039cost circRNAs were not associated with translating ribosomes, therefore, circRNAs were deemed to be noncoding. However, the latest research findings revealed that some circRNAs could generate proteins in vivo, which expands the landscape of transcriptome and proteome" ], "type": "summary", "id": "5a895a96fcd1d6a10c000003", "snippets": [ { "offsetInBeginSection": 224, "offsetInEndSection": 356, "text": "However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Circular RNAs (circRNAs) are long, non-coding RNAs that result from the non-canonical splicing of linear pre-mRNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26649774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Circular RNAs (circRNAs) are a large type of noncoding RNAs characterized by their circular shape resulting from covalently closed continuous loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26874353", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 720, "text": "They are known to serve as microRNA (miRNA) sponges, regulators of alternative splicing, transcription factors and encode for proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26874353", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 306, "text": "Covalently closed loop structures elevate the stability of this new type of noncoding RNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27255916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Circular RNAs (circRNAs) are a novel class of non-coding RNA that assumes a covalently closed continuous conformation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Circular RNAs (circRNAs) represent a large class of noncoding RNAs (ncRNAs) that have recently emerged as regulators of gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27612318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Circular RNAs (circRNAs) are highly abundant and evolutionarily conserved non-coding RNAs produced by circularization of specific exons. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27892769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28344082", "endSection": "title" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1106, "text": " Circ-ZNF609 is associated with heavy polysomes, and it is translated into a protein in a splicing-dependent and cap-independent manner, providing an example of a protein-coding circRNA in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28344082", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 996, "text": "Altogether, our study provides strong evidence for translation of circRNAs, revealing the existence of an unexplored layer of gene activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28344080", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 834, "text": "In addition, most circRNAs were not associated with translating ribosomes, therefore, circRNAs were deemed to be noncoding. However, the latest research findings revealed that some circRNAs could generate proteins in vivo, which expands the landscape of transcriptome and proteome. To gain insights into the new area of circRNA translation, we introduce an integrated tool capable of detecting circRNAs with protein-coding potential from high-throughput sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028266", "endSection": "abstract" } ] }, { "body": "What is the phenomenon of gene kissing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17346703", "http://www.ncbi.nlm.nih.gov/pubmed/19106226", "http://www.ncbi.nlm.nih.gov/pubmed/23099887", "http://www.ncbi.nlm.nih.gov/pubmed/17223284" ], "ideal_answer": [ "Clustering of genes with similar expression patterns constitutes a phenomenon sometimes called \"gene kissing.\"", "This positioning can also result in the clustering of genes with similar expression patterns, a phenomenon sometimes called \"gene kissing.\" ", "This positioning can also result in the clustering of genes with similar expression patterns, a phenomenon sometimes called \"gene kissing.\" We speculate that our findings might provide insight into other types of gene kissing, some of which also require cis-acting DNA sequences and trans-acting proteins." ], "type": "summary", "id": "5a896a06fcd1d6a10c000006", "snippets": [ { "offsetInBeginSection": 135, "offsetInEndSection": 275, "text": "This positioning can also result in the clustering of genes with similar expression patterns, a phenomenon sometimes called \"gene kissing.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099887", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1049, "text": "We speculate that our findings might provide insight into other types of gene kissing, some of which also require cis-acting DNA sequences and trans-acting proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099887", "endSection": "abstract" }, { "offsetInBeginSection": 1915, "offsetInEndSection": 2132, "text": "The imposition at a distance of new chromatin structures with regulatory impact can occur in cis as well as in trans, and is examined as intrachromosomally spreading teleregulation and interchromosomal \"gene kissing\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17223284", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 721, "text": "Instances of 2 different alleles touching each other were found in 20-47% of nuclei depending on the tissue. The frequency of such \"kissing\" events was not significantly different in cells expressing a high proportion of the Hox clusters when compared to cells expressing none or only a few Hox genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346703", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 871, "text": "We found that the HoxB and HoxC clusters, which are located in gene-rich regions, were involved more frequently in gene kissing in embryonic nuclei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17346703", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 274, "text": "This positioning can also result in the clustering of genes with similar expression patterns, a phenomenon sometimes called \"gene kissing.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099887", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1053, "text": "We speculate that our findings might provide insight into other types of gene kissing, some of which also require cis-acting DNA sequences and trans-acting proteins.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1032, "text": "genomes are spatially organized on many levels and the positioning of genes within the nucleus contributes to their proper expression this positioning can also result in the clustering of genes with similar expression patterns a phenomenon sometimes called gene kissing we have found that yeast genes are targeted to the nuclear periphery through interaction of the nuclear pore complex with small cis acting dna zip codes in their promoters our recent study demonstrated that genes with the same zip codes cluster together at the nuclear periphery the zip codes were necessary and sufficient to induce interchromosomal clustering finally we identified a transcription factor put3 that binds to the grs i zip code put3 binds to grs i and is required for both grs i dependent positioning at the nuclear periphery and interchromosomal clustering of grs i targeted genes we speculate that our findings might provide insight into other types of gene kissing some of which also require cis acting dna sequences and trans acting proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099887", "endSection": "abstract" } ] }, { "body": "What protein is the most common cause of hereditary renal amyloidosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9389696", "http://www.ncbi.nlm.nih.gov/pubmed/19073821", "http://www.ncbi.nlm.nih.gov/pubmed/19013120", "http://www.ncbi.nlm.nih.gov/pubmed/8097946", "http://www.ncbi.nlm.nih.gov/pubmed/26299174", "http://www.ncbi.nlm.nih.gov/pubmed/15523923", "http://www.ncbi.nlm.nih.gov/pubmed/29142973", "http://www.ncbi.nlm.nih.gov/pubmed/23551149", "http://www.ncbi.nlm.nih.gov/pubmed/25331409", "http://www.ncbi.nlm.nih.gov/pubmed/8113408" ], "ideal_answer": [ "The most common cause of hereditary renal amyloidosis is over expression of a mutant form of the Fibrinogen A Alpha protein" ], "exact_answer": [ "Fibrinogen A Alpha protein" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D028226", "https://meshb.nlm.nih.gov/record/ui?ui=D000686" ], "type": "factoid", "id": "5a6a02a3b750ff4455000021", "snippets": [ { "offsetInBeginSection": 15, "offsetInEndSection": 227, "text": "ibrinogen A alpha chain amyloidosis is an autosomal dominant disease associated with mutations in the fibrinogen A alpha chain (FGA) gene, and it is the most common cause of hereditary renal amyloidosis in the UK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29142973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Hereditary renal amyloidosis is an autosomal dominant condition with considerable overlap with other amyloidosis type", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26299174", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 605, "text": "We suspected amyloidosis with fibrinogen A alpha chain deposits, which is the most frequent cause of hereditary amyloidosis in Europe, with a glomerular preferential affectation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26299174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Three members of a family who died with renal amyloidosis were found to share a single nucleotide substitution in the fibrinogen alpha-chain gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8097946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A French kindred with autosomal dominant hereditary renal amyloidosis was found to have a novel mutation in the fibrinogen Aalpha-chain gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9389696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Two families with hereditary renal amyloidosis were found to have a novel mutation in the fibrinogen A alpha chain gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8113408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The predominant cause of hereditary renal amyloidosis is a mutation of the fibrinogen Aalpha chain (AFib), the most common being the E526V mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19013120", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1295, "text": "Discovery of this new mutation confirms the association between fibrinogen A alpha chain variant and hereditary renal amyloidosis and establishes a new biochemical subtype of amyloidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8113408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8097946", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Mutations in the fibrinogen A\u03b1-chain genes are the most common cause of hereditary renal amyloidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25331409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Mutant fibrinogen A-alpha-chain associated with hereditary renal amyloidosis and peripheral neuropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15523923", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Mutations in the fibrinogen A alpha-chain gene are the most common cause of hereditary renal amyloidosis in the United Kingdom.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19073821", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Introduction Fibrinogen A alpha chain amyloidosis is an autosomal dominant disease associated with mutations in the fibrinogen A alpha chain (FGA) gene, and it is the most common cause of hereditary renal amyloidosis in the UK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29142973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Mutations in the fibrinogen A\u03b1-chain genes are the most common cause of hereditary renal amyloidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25331409", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 144, "text": "Hereditary amyloidosis with predominant renal disease can be caused by mutations in the gene encoding the fibrinogen A\u03b1-chain (AFib)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23551149", "endSection": "abstract" } ] }, { "body": "What are the side effects of deflazacort in DMD patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28043681" ], "ideal_answer": [ "The side effects observed in DMD patients following deflazacort treatment include growth failure and weight gain, facial fullness, blood pressure, bone health, cataracts, gastrointestinal symptoms, behavior, hypertrichosis, and need for medication interventions." ], "exact_answer": [ [ "growth failure" ], [ "weight gain" ], [ "facial fullness" ], [ "blood pressure" ], [ "bone health" ], [ "cataracts" ], [ "gastrointestinal symptoms" ], [ "behavioral" ], [ "hypertrichosis" ], [ "need for medical intervention" ] ], "type": "list", "id": "5a7727f39e632bc06600000d", "snippets": [ { "offsetInBeginSection": 575, "offsetInEndSection": 773, "text": "Side effects were growth failure and weight gain, facial fullness, blood pressure, bone health, cataracts, gastrointestinal symptoms, behavior, hypertrichosis, and need for medication interventions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28043681", "endSection": "abstract" } ] }, { "body": "With which cancers has the loss of SMARCB1 been associated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28825187", "http://www.ncbi.nlm.nih.gov/pubmed/28427232", "http://www.ncbi.nlm.nih.gov/pubmed/27635948", "http://www.ncbi.nlm.nih.gov/pubmed/24983247", "http://www.ncbi.nlm.nih.gov/pubmed/28812319" ], "ideal_answer": [ "Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1 Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs)", "We therefore sought to identify novel mutations to better understand chordoma biology and to potentially identify therapeutic targets Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1", "The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC) Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs)", "Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs).", "Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1. Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas . The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas . " ], "exact_answer": [ "chordomas", "childhood chordomas", "infantile chordomas", "CCs" ], "type": "factoid", "id": "5a86f074faa1ab7d2e00003a", "snippets": [ { "offsetInBeginSection": 71, "offsetInEndSection": 204, "text": "We therefore sought to identify novel mutations to better understand chordoma biology and to potentially identify therapeutic targets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983247", "endSection": "title" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1884, "text": "When this data is paired with the studies showing 18 of 21 chordoma samples displaying copy loss at the locus for CDKN2A, 17 of 21 chordoma samples displaying copy loss at PTEN, and 3 of 4 chordoma samples displaying deletion at the SMARCB1 locus, we can infer that a loss of heterozygosity at these three loci may play a significant role in chordoma pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "SMARCB1/INI1 Involvement in Pediatric Chordoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27635948", "endSection": "title" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1170, "text": "All 8 cases were positive for brachyury, whereas there was no nuclear SMARCB1/INI1 expression in 4 of the 8 cases, including the poorly differentiated chordoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27635948", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 722, "text": " In this study, we considered immunohistochemistry and SMARCB1/INI1 mutational status to examine SMARCB1 status in a series of pediatric chordomas (7 classic and 1 poorly differentiated)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27635948", "endSection": "abstract" }, { "offsetInBeginSection": 1643, "offsetInEndSection": 1703, "text": "pathogenic involvement of SMARCB1/INI1 in childhood chordoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27635948", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 380, "text": "The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28427232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28825187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Poorly differentiated chordoma with loss of SMARCB1/INI1 expression in pediatric patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28812319", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Identification of loss of SMARCB1/INI1 expression in poorly differentiated (PD) chordoma in pediatric patients suggests that PD chordoma is an entity molecularly distinct from conventional chordoma or atypical teratoid/rhabdoid tumor, which is also characterized by loss of SMARCB1/INI1 expression by inactivating mutation of the SMARCB1/INI gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28812319", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 452, "text": "So far, around 20 cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression have been reported", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28812319", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 596, "text": "Here, we report two cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression, which is very rare among the pediatric chordoma types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28812319", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1336, "text": "Based on the clival location and histologic findings along with the loss of SMARCB1/INI1 expression and positivity for nuclear brachyury staining, the final pathologic diagnosis for both cases was PD chordoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28812319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28825187", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 381, "text": "The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28427232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 801, "text": "loss of smarcb1 ini1 expression is considered to be a hallmark for childhood chordomas ccs although mutation loss of 22q has strongly established the loss of smarcb1 ini1 in cancers the cause in ccs remains elusive recent studies suggest role of mirnas in regulation of smarcb1 ini1 expressions we examined 5 reported target predicted mirnas to smarcb1 ini1 in smarcb1 ini1 immunonegative and immunopositive cases and found upregulation of mir 671 5p and mir 193a 5p in smarcb1 ini1 immunonegative cases notably these two mirnas were significantly predicted to target tgf \u03b2 signaling suggestive of dysregulation of developmental and osteoblast regulation pathway in ccs overall we suggest mir 671 5p and mir 193a 5p mediated epigenetic mode of smarcb1 ini1 loss and downregulated tgf \u03b2 pathway in ccs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28825187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "smarcb1 ini1 involvement in pediatric chordoma a mutational and immunohistochemical analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27635948", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1725, "text": "chordomas arise in the skull base and spine and usually occur in adults and are rare in the pediatric population cases of chordoma in pediatric age are often poorly differentiated showing cytologic atypia increased cellularity and mitosis and their aggressive behavior is associated with a high incidence of metastatic spread and a short patient survival recent studies have described loss of smarcb1 ini1 protein in poorly differentiated chordomas associated not with point mutations but with smarcb1 ini1 gene deletions instead in this study we considered immunohistochemistry and smarcb1 ini1 mutational status to examine smarcb1 status in a series of pediatric chordomas 7 classic and 1 poorly differentiated we performed immunohistochemical tests for ini1 brachyury s100 and cytokeratins and conducted a genetic analysis on the smarcb1 coding sequence nm 003073 using the sanger method and multiplex ligation dependent probe amplification to detect abnormal copy numbers of the gene locus all 8 cases were positive for brachyury whereas there was no nuclear smarcb1 ini1 expression in 4 of the 8 cases including the poorly differentiated chordoma genetic analysis identified a missense mutation in 2 cases and a nonsense mutation associated with loss of smarcb1 ini1 protein and features of poorly differentiated tumor in 1 these mutations were novel variants occurring in heterozygosity and they were judged to be pathogenic by 3 different bioinformatic tools in 7 of 8 cases we performed multiplex ligation dependent probe amplification and 3 cases showed deletions at the smarcb1 locus our results confirm the pathogenic involvement of smarcb1 ini1 in childhood chordoma we also describe 3 novel pathogenic mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27635948", "endSection": "abstract" } ] }, { "body": "Where do centromeres locate according to the Rabl orientation of eukaryotic nuclei?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14555468", "http://www.ncbi.nlm.nih.gov/pubmed/24424980", "http://www.ncbi.nlm.nih.gov/pubmed/20501974", "http://www.ncbi.nlm.nih.gov/pubmed/3219911", "http://www.ncbi.nlm.nih.gov/pubmed/10806101", "http://www.ncbi.nlm.nih.gov/pubmed/11559751" ], "ideal_answer": [ "The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres.", "The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres. telomeric Yq12 sequence also localized together with perinucleolar centromeres in a completely non-Rabl orientation. During interphase in the budding yeast, Saccharomyces cerevisiae, centromeres are clustered near one pole of the nucleus as a rosette with the spindle pole body at its hub. We show that most of this preferential association is not due to vegetative (also known as somatic) pairing but is caused by the polar orientation of interphase chromosomes (Rabl orientation) This was taken as good evidence for the maintenance of the chromosome arrangement - the Rabl orientation - and of the peripheral location of the centromere and its association with the nuclear membrane. Homologous chromosomes were spatially separated in nuclei.", "the nuclear membrane", "This was taken as good evidence for the maintenance of the chromosome arrangement - the Rabl orientation - and of the peripheral location of the centromere and its association with the nuclear membrane." ], "type": "summary", "id": "5a89528dfcd1d6a10c000001", "snippets": [ { "offsetInBeginSection": 1325, "offsetInEndSection": 1527, "text": "This was taken as good evidence for the maintenance of the chromosome arrangement - the Rabl orientation - and of the peripheral location of the centromere and its association with the nuclear membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424980", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1800, "text": "Within this general arrangement homologous telocentric chromosomes were frequently seen to have their centromeres associated or directed towards each other. The role of the centromere in somatic association as a spindle fibre attachment and chromosome binder is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424980", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 776, "text": "Homologous chromosomes were spatially separated in nuclei. In large neurons, probes specific for 9q12, or 1q12 showed that at least one homolog was always compartmentalized together with centromeres on the nucleolus, while the second signal either abutted the nucleolus or was on the nuclear membrane", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3219911", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 896, "text": " telomeric Yq12 sequence also localized together with perinucleolar centromeres in a completely non-Rabl orientation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3219911", "endSection": "abstract" }, { "offsetInBeginSection": 1762, "offsetInEndSection": 1973, "text": "We suggest that centromeric and other highly repeated non-transcribed sequence domains may act as general organizing centers for cell type specific interphase patterns that are conserved in mammalian evolution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3219911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Centromere clustering is a major determinant of yeast interphase nuclear organization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10806101", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "During interphase in the budding yeast, Saccharomyces cerevisiae, centromeres are clustered near one pole of the nucleus as a rosette with the spindle pole body at its hub.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10806101", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 845, "text": "Unlike the Rabl-orientation known from many higher eukaryotes, centromere clustering in yeast is not only a relic of anaphase chromosome polarization, because it can be reconstituted without the passage of cells through anaphase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10806101", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 252, "text": "The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11559751", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 573, "text": "We show that most of this preferential association is not due to vegetative (also known as somatic) pairing but is caused by the polar orientation of interphase chromosomes (Rabl orientation)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14555468", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1641, "text": "These developments are discussed in this contribution, with particular reference to the centromere and the nucleolus organizer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20501974", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 251, "text": "The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11559751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1175, "text": "chromosomes are not packed randomly in the nucleus the rabl orientation is an example of the non random arrangement of chromosomes centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres this orientation is established during mitosis and maintained through subsequent interphase in a range of species we report that a rabl like configuration can be formed de novo without a preceding mitosis during the transition from the sexual phase to the vegetative phase of the life cycle in fission yeast in this process each of the dispersed centromeres is often associated with a novel sad1 containing body that is contacting a cytoplasmic microtubule laterally sad1 is a component of the spindle pole body spb the sad1 containing body was colocalized with other known spb components kms1 and spo15 but not with cut12 indicating that it represents a novel spb related complex the existence of the triplex structure centromere microtubule sad1 body suggests that the clustering of centromeres is controlled by a cytoplasmic microtubular system accordingly when microtubules are destabilized clustering is markedly reduced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11559751", "endSection": "abstract" } ] }, { "body": "What is the function of STAR elements in yeast telomeres?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10228167", "http://www.ncbi.nlm.nih.gov/pubmed/21949764", "http://www.ncbi.nlm.nih.gov/pubmed/10228166", "http://www.ncbi.nlm.nih.gov/pubmed/23380569", "http://www.ncbi.nlm.nih.gov/pubmed/21437278" ], "ideal_answer": [ "Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs). We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR. The telomere-proximal portion of either X or Y' dampened silencing when located between the telomere and the reporter gene. These elements were named STARs, for subtelomeric anti-silencing regions. STARs can also counteract silencer-driven repression at the mating-type HML locus. When two STARs bracket a reporter gene, its expression is no longer influenced by surrounding silencing elements, although these are still active on a second reporter gene.", "These elements were named STARs, for subtelomeric anti-silencing regions. Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs). We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR. In addition, an intervening STAR uncouples the silencing of neighboring genes. The telomere-proximal portion of either X or Y' dampened silencing when located between the telomere and the reporter gene. STARs thus display the hallmarks of insulators.", "Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs).", "Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs). We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR.", "STARs are subtelomeric anti-silencing regions that can counteract silencer-driven repression at the mating-type HML locus. When two STARs bracket a reporter gene, its expression is no longer influenced by surrounding silencing elements, although these are still active on a second reporter gene. In addition, an intervening STAR uncouples the silencing of neighboring genes. STARs thus display the hallmarks of insulators." ], "type": "summary", "id": "5a870b7bfaa1ab7d2e00003d", "snippets": [ { "offsetInBeginSection": 247, "offsetInEndSection": 318, "text": "Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21437278", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 835, "text": "We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21437278", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 787, "text": " The telomere-proximal portion of either X or Y' dampened silencing when located between the telomere and the reporter gene. These elements were named STARs, for subtelomeric anti-silencing regions. STARs can also counteract silencer-driven repression at the mating-type HML locus. When two STARs bracket a reporter gene, its expression is no longer influenced by surrounding silencing elements, although these are still active on a second reporter gene. In addition, an intervening STAR uncouples the silencing of neighboring genes. STARs thus display the hallmarks of insulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10228166", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1386, "text": "Thus the STAR and TEF2-UASrpg boundary elements inhibit chromatin silencing through an antisilencing activity independently of their position or orientation in S. cerevisiae minichromosomes rather than by creating a position-specific barrier as seen in the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21949764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Cohabitation of insulators and silencing elements in yeast subtelomeric regions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10228166", "endSection": "title" }, { "offsetInBeginSection": 660, "offsetInEndSection": 836, "text": "We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21437278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1235, "text": "in budding yeast the telomeric dna is flanked by a combination of two subtelomeric repetitive sequences the x and y elements we have investigated the influence of these sequences on telomeric silencing the telomere proximal portion of either x or y dampened silencing when located between the telomere and the reporter gene these elements were named stars for subtelomeric anti silencing regions stars can also counteract silencer driven repression at the mating type hml locus when two stars bracket a reporter gene its expression is no longer influenced by surrounding silencing elements although these are still active on a second reporter gene in addition an intervening star uncouples the silencing of neighboring genes stars thus display the hallmarks of insulators protection from silencing is recapitulated by multimerized oligonucleotides representing tbf1p and reb1p binding sites as found in stars in contrast sequences located more centromere proximal in x and y elements reinforce silencing they can promote silencing downstream of an insulated expressed domain overall our results suggest that the silencing emanating from telomeres can be propagated in a discontinuous manner via a series of subtelomeric relay elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10228166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "cohabitation of insulators and silencing elements in yeast subtelomeric regions", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10228166", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "limitations of silencing at native yeast telomeres", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10228167", "endSection": "title" } ] }, { "body": "Name the phase 3 clinical trials for tofacitinib in colitis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28467869" ], "ideal_answer": [ "There are three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis: OCTAVE Induction 1, OCTAVE Induction 2, OCTAVE Sustain.", "OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 ." ], "exact_answer": [ [ "OCTAVE Induction 1" ], [ "OCTAVE Induction 2" ], [ "OCTAVE Sustain" ] ], "type": "list", "id": "5a75fbf383b0d9ea6600000a", "snippets": [ { "offsetInBeginSection": 269, "offsetInEndSection": 742, "text": "We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 1010, "text": "In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1902, "text": "In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 2406, "offsetInEndSection": 2570, "text": "Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 2256, "offsetInEndSection": 2572, "text": "In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" } ] }, { "body": "What is the mode of action of the drug Prolia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19836866", "http://www.ncbi.nlm.nih.gov/pubmed/25509894", "http://www.ncbi.nlm.nih.gov/pubmed/22023901" ], "ideal_answer": [ "Prolia, also known as denosumab is an anti-RANKL agent for the treatment of osteoporosis. It works by preventing the development of osteoclasts which are cells that break down bone." ], "exact_answer": [ "Anti-RANKL antibody which prevents bone catabolism in osteoporosis" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000069448" ], "type": "factoid", "id": "5a70ce82b750ff4455000065", "snippets": [ { "offsetInBeginSection": 231, "offsetInEndSection": 464, "text": "Recently anti-RANKL agents (receptor activator of nuclear factor-kappaB ligand) such as denosumab (Prolia, Amgen Inc., California, USA) that have a similar mode of action to bisphosphonates have been introduced to treat such diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19836866", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 465, "text": "Recently anti-RANKL agents (receptor activator of nuclear factor-kappaB ligand) such as denosumab (Prolia, Amgen Inc., California, USA) that have a similar mode of action to bisphosphonates have been introduced to treat such diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19836866", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 252, "text": "To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25509894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Denosumab (Prolia) is a fully human monoclonal antibody directed against receptor activator of nuclear factor-\u03baB ligand (RANKL), which interferes with the formation, activation, and survival of osteoclasts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22023901", "endSection": "title" } ] }, { "body": "How does parathyroid hormone affect circulating levels of periostin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20654714", "http://www.ncbi.nlm.nih.gov/pubmed/22927401" ], "ideal_answer": [ "Parathyroid hormone can upregulate periostin levels." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0071107", "http://www.uniprot.org/uniprot/POSTN_MOUSE", "http://www.uniprot.org/uniprot/POSTN_HUMAN", "https://meshb.nlm.nih.gov/record/ui?ui=D010281" ], "type": "summary", "id": "5a6f7138b750ff445500004f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22927401", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 987, "text": "In addition, periostin mRNA was transiently up-regulated in osteoblasts by PTH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20654714", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 889, "text": "PTH stimulated periostin and inhibited MEF2C and sclerostin (Sost) expression in bone and osteoblasts in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22927401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "periostin is a collagen associated bone matrix protein regulated by parathyroid hormone", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20654714", "endSection": "title" } ] }, { "body": "What is MINDY (motif interacting with Ub-containing novel DUB family)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27292798" ], "ideal_answer": [ "MINDY-1 is a member of an evolutionarily conserved and structurally distinct new family of deubiquitinating enzymes." ], "type": "summary", "id": "5a6d13fbb750ff445500002f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292798", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 417, "text": "Deubiquitinating enzymes (DUBs) remove ubiquitin (Ub) from Ub-conjugated substrates to regulate the\u00a0functional outcome of ubiquitylation. Here we report the discovery of a new family of DUBs, which we have named MINDY (motif interacting with Ub-containing novel DUB family). Found in all eukaryotes, MINDY-family DUBs are highly selective at cleaving K48-linked polyUb, a signal that targets proteins for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292798", "endSection": "abstract" } ] }, { "body": "Has the proteome of mice hippocampus been analysed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26549202", "http://www.ncbi.nlm.nih.gov/pubmed/28775826", "http://www.ncbi.nlm.nih.gov/pubmed/26977433", "http://www.ncbi.nlm.nih.gov/pubmed/27378549", "http://www.ncbi.nlm.nih.gov/pubmed/27001617" ], "ideal_answer": [ "Yes, numerous proteomic studies of mice hippcampi has been performed." ], "exact_answer": "yes", "type": "yesno", "id": "5a8881118cb19eca6b000006", "snippets": [ { "offsetInBeginSection": 738, "offsetInEndSection": 972, "text": "We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26549202", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 359, "text": " We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/-mice, a model of the 22q11.2 deletion syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27001617", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 1033, "text": " Molecular alterations in the frontal cortex and hippocampus ofTsc1+/-and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MSE) was employed as an unbiased method to detect changes in protein levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28775826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "This dataset reports on the analysis of mouse hippocampus by LC-MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26977433", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 567, "text": "Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 \u00d7 Tg-AD mice, a widely used animal model of AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27378549", "endSection": "abstract" } ] }, { "body": "Was saracatinib being considered as a treatment for Alzheimer's disease in November 2017?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25874001" ], "ideal_answer": [ "Yes, saracatinib is being studied as a treatment against Alzheimer's Disease. A clinical Phase Ib study has been completed, and a clinical Phase IIa study is ongoing." ], "exact_answer": "yes", "type": "yesno", "id": "5a772e9dfaa1ab7d2e000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "endSection": "title" }, { "offsetInBeginSection": 599, "offsetInEndSection": 801, "text": "Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1192, "text": "The study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26. A total of 24 subjects were recruited in three sequential groups, with each randomized to receive oral AZD0530 at doses of 50\u00a0mg, 100\u00a0mg, 125\u00a0mg, or placebo daily for 4\u00a0weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "endSection": "abstract" }, { "offsetInBeginSection": 2307, "offsetInEndSection": 2657, "text": "AZD0530 is reasonably safe and well tolerated in patients with mild-to-moderate AD, achieving substantial central nervous system penetration with oral dosing at 100-125\u00a0mg. Targeting Fyn kinase may be a promising therapeutic approach in AD, and a larger Phase IIa clinical trial of AZD0530 for the treatment of patients with AD has recently launched.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "endSection": "abstract" } ] }, { "body": "Are mouse chromosomes acrocentric?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9177778", "http://www.ncbi.nlm.nih.gov/pubmed/8896561", "http://www.ncbi.nlm.nih.gov/pubmed/6177004", "http://www.ncbi.nlm.nih.gov/pubmed/6538846", "http://www.ncbi.nlm.nih.gov/pubmed/100785", "http://www.ncbi.nlm.nih.gov/pubmed/3248380", "http://www.ncbi.nlm.nih.gov/pubmed/2767161", "http://www.ncbi.nlm.nih.gov/pubmed/7606923" ], "ideal_answer": [ "yes", "Mouse chromosomes are acrocentric and of similar size." ], "exact_answer": "yes", "type": "yesno", "id": "5a89537cfcd1d6a10c000002", "snippets": [ { "offsetInBeginSection": 692, "offsetInEndSection": 950, "text": " Based on combined fluorescence in situ hybridization and linkage mapping, the gene order on CFA9 is similar to that of the homologous genes on HSA17q and mouse chromosome 11 (MMU11), but in the dog the gene order is inverted with respect to the centromere. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9177778", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 435, "text": "In murine models of human carcinogenesis, however, karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8896561", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 359, "text": "The minor satellite is closer to the short arms of the acrocentric chromosomes than the major satellite", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2767161", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 584, "text": " These cells contain Robertsonian translocated chromosomes 1 and 7 as the only submetacentric chromosome in an otherwise acrocentric genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3248380", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 452, "text": " The resulting metacentric chromosomes are very different in size and in morphology from normal mouse acrocentric chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6538846", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 552, "text": " Because of 35 independent primary hybrids used in this study were derived from two types of feral mice, each with a different combination of Robertsonian translocation chromosomes, as well as from mice with a normal complement of acrocentric chromosomes, analysis of 16 selected mouse enzyme markers provided data on the segregation of all 20 mouse chromosomes in these hybrids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6177004", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 416, "text": "The two mouse stocks exhibit karyotypes consisting of nine pairs of metacentric chromosomes as a result of centric fusions of acrocentric chromosomes in different combinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/100785", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Physical gene mapping by in situ hybridization is a difficult task in an all-acrocentric mouse karyotype, because all of the chromosomes are morphologically very similar.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7606923", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 452, "text": "The resulting metacentric chromosomes are very different in size and in morphology from normal mouse acrocentric chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6538846", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1673, "text": "murine models of human carcinogenesis are exceedingly valuable tools to understand genetic mechanisms of neoplastic growth the identification of recurrent chromosomal rearrangements by cytogenetic techniques serves as an initial screening test for tumour specific aberrations in murine models of human carcinogenesis however karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size fluorescence in situ hybridization fish with mouse chromosome specific painting probes can complement conventional banding analysis although sensitive and specific fish analyses are restricted to the visualization of only a few mouse chromosomes at a time here we apply a novel imaging technique that we developed recently for the visualization of human chromosomes to the simultaneous discernment of all mouse chromosomes the approach is based on spectral imaging to measure chromosome specific spectra after fish with differentially labelled mouse chromosome painting probes utilizing a combination of fourier spectroscopy ccd imaging and conventional optical microscopy spectral imaging allows simultaneous measurement of the fluorescence emission spectrum at all sample points a spectrum based classification algorithm has been adapted to karyotype mouse chromosomes we have applied spectral karyotyping sky to chemically induced plasmocytomas mammary gland tumours from transgenic mice overexpressing the c myc oncogene and thymomas from mice deficient for the ataxia telangiectasia atm gene results from these analyses demonstrate the potential of sky to identify complex chromosomal aberrations in mouse models of human carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8896561", "endSection": "abstract" } ] }, { "body": "Is overproduction of transthyretin is associated with amyloidosis associated neuropathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28920433", "http://www.ncbi.nlm.nih.gov/pubmed/27919414", "http://www.ncbi.nlm.nih.gov/pubmed/28646538", "http://www.ncbi.nlm.nih.gov/pubmed/28922609", "http://www.ncbi.nlm.nih.gov/pubmed/28802308", "http://www.ncbi.nlm.nih.gov/pubmed/28598015", "http://www.ncbi.nlm.nih.gov/pubmed/26243339" ], "ideal_answer": [ "Yes, an overproduction of transthyretin is associated with amyloidosis associated neuropathy.", "Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a disease caused by the deposit of abnormal transthyretin on tissues, mainly nerves" ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:870", "https://meshb.nlm.nih.gov/record/ui?ui=D000686", "https://meshb.nlm.nih.gov/record/ui?ui=D028227", "https://meshb.nlm.nih.gov/record/ui?ui=D028226", "http://www.uniprot.org/uniprot/TTHY_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:0050638" ], "type": "yesno", "id": "5a6e47b1b750ff4455000049", "snippets": [ { "offsetInBeginSection": 28, "offsetInEndSection": 181, "text": "Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a disease caused by the deposit of abnormal transthyretin on tissues, mainly nerves", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27919414", "endSection": "abstract" }, { "offsetInBeginSection": 30, "offsetInEndSection": 75, "text": "transthyretin familial amyloid polyneuropathy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28598015", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "We report a new transthyretin (ATTR) gene c.272C>G mutation and variant protein, p.Leu32Val, in a kindred of Bolivian origin with a rapid progressive peripheral neuropathy and cardiomyopat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28646538", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28802308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Abnormal deposition of aggregated wild-type (WT) human transthyretin (TTR) and its pathogenic variants is responsible for cardiomyopathy and neuropathy related to TTR amyloidosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28920433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues. Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28922609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28802308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Hereditary transthyretin amyloidosis (ATTR) is usually characterised by a progressive peripheral and autonomic neuropathy often with associated cardiac failure and is due to dominantly inherited transthyretin mutations causing accelerated amyloid deposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26243339", "endSection": "abstract" } ] }, { "body": "What is cebocephaly", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16061113", "http://www.ncbi.nlm.nih.gov/pubmed/23599105", "http://www.ncbi.nlm.nih.gov/pubmed/19673365", "http://www.ncbi.nlm.nih.gov/pubmed/2255999" ], "ideal_answer": [ "Cebocephaly is a developmental anomaly of the head characterized by a small head, with a defective small, flattened nose with a single nostril or absent nose and closely set eyes." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D019465", "https://meshb.nlm.nih.gov/record/ui?ui=D009139" ], "type": "summary", "id": "5a87124561bb38fb24000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Cebocephaly is a very rare congenital midline facial anomaly characterized by a blind-ended single nostril and ocular hypotelorism, and is usually combined with alobar holoprosencephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19673365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "Cebocephaly (hypotelorism, single-nostril nose) and ethmocephaly (hypotelorism, interorbital proboscis) lie in the middle of the spectrum of craniofacial changes associated with holoprosencephaly. Because these defects and thorough anatomic studies of them are rare, knowledge concerning morphologic as well as pathogenetic relationships is lacking. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2255999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Cebocephaly (hypotelorism, single-nostril nose) and ethmocephaly (hypotelorism, interorbital proboscis) lie in the middle of the spectrum of craniofacial changes associated with holoprosencephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2255999", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 296, "text": "Patients with cebocephaly have ocular hypotelorism and a proboscis with a single, blind-ended nostril.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23599105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Cebocephaly is a very rare congenital anomaly combining a severe midline facial malformation and holoprosencephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16061113", "endSection": "abstract" } ] }, { "body": "How can network assortativity be applied in the three-dimensional analysis of the genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "http://www.ncbi.nlm.nih.gov/pubmed/25121490" ], "ideal_answer": [ "Chromatin assortativity is a way to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts." ], "type": "summary", "id": "5a8863948cb19eca6b000002", "snippets": [ { "offsetInBeginSection": 1641, "offsetInEndSection": 1923, "text": "Here, we use publicly available DNaseI-seq data to measure the assortativity signatures of genome-wide TFNs in 41 distinct human cell and tissue types. We find that all TFNs share a common assortativity signature and that this signature confers phenotypic robustness to model TFNs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25121490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "title" }, { "offsetInBeginSection": 83, "offsetInEndSection": 445, "text": "Assortativity is a network property used in social sciences to identify factors affecting how people establish social ties. We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1074, "text": "Polycomb group proteins and associated histone marks are the features with the highest chromatin assortativity in promoter-centered networks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1390, "text": "We observe higher chromatin assortativity of the actively elongating form of RNA polymerase 2 (RNAPII) compared with inactive forms only in interactions between promoters and other elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "abstract" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1792, "text": "Here, we use publicly available DNaseI-seq data to measure the assortativity signatures of genome-wide TFNs in 41 distinct human cell and tissue types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25121490", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 445, "text": "We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "abstract" }, { "offsetInBeginSection": 1668, "offsetInEndSection": 1839, "text": "Our approach facilitates the study of multiple genome-wide epigenomic profiles, considering network topology and allowing the comparison of chromatin interaction networks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1787, "text": "network analysis is a powerful way of modeling chromatin interactions assortativity is a network property used in social sciences to identify factors affecting how people establish social ties we propose a new approach using chromatin assortativity to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts we use high resolution promoter capture hi c and hi cap data as well as chia pet data from mouse embryonic stem cells to investigate promoter centered chromatin interaction networks and calculate the presence of specific epigenomic features in the chromatin fragments constituting the nodes of the network we estimate the association of these features with the topology of four chromatin interaction networks and identify features localized in connected areas of the network polycomb group proteins and associated histone marks are the features with the highest chromatin assortativity in promoter centered networks we then ask which features distinguish contacts amongst promoters from contacts between promoters and other genomic elements we observe higher chromatin assortativity of the actively elongating form of rna polymerase 2 rnapii compared with inactive forms only in interactions between promoters and other elements contacts among promoters and between promoters and other elements have different characteristic epigenomic features we identify a possible role for the elongating form of rnapii in mediating interactions among promoters enhancers and transcribed gene bodies our approach facilitates the study of multiple genome wide epigenomic profiles considering network topology and allowing the comparison of chromatin interaction networks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "integrating epigenomic data and 3d genomic structure with a new measure of chromatin assortativity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27391817", "endSection": "title" } ] }, { "body": "Which phase III clinical trials for rheumatoid arthritis involve baricitinib? (November 2017)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27799159", "http://www.ncbi.nlm.nih.gov/pubmed/27689735", "http://www.ncbi.nlm.nih.gov/pubmed/28798049" ], "ideal_answer": [ "The phase 3 clinical trials of baricitinib in rheumatoid arthritis patients are: RA-BEACON, RA-BUILD, RA-BEAM." ], "exact_answer": [ [ "RA-BEACON" ], [ "RA-BUILD" ], [ "RA-BEAM" ] ], "type": "list", "id": "5a76155c83b0d9ea6600001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799159", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27689735", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28798049", "endSection": "title" } ] }, { "body": "Which disease risk can be estimated with the Stop-Bang questionnaire?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24917451", "http://www.ncbi.nlm.nih.gov/pubmed/25758298", "http://www.ncbi.nlm.nih.gov/pubmed/27610133", "http://www.ncbi.nlm.nih.gov/pubmed/28207464", "http://www.ncbi.nlm.nih.gov/pubmed/27886561", "http://www.ncbi.nlm.nih.gov/pubmed/25926368", "http://www.ncbi.nlm.nih.gov/pubmed/26961117", "http://www.ncbi.nlm.nih.gov/pubmed/26547116", "http://www.ncbi.nlm.nih.gov/pubmed/25081584", "http://www.ncbi.nlm.nih.gov/pubmed/25010615", "http://www.ncbi.nlm.nih.gov/pubmed/25182345", "http://www.ncbi.nlm.nih.gov/pubmed/28283367", "http://www.ncbi.nlm.nih.gov/pubmed/26658438", "http://www.ncbi.nlm.nih.gov/pubmed/22270686", "http://www.ncbi.nlm.nih.gov/pubmed/27919588", "http://www.ncbi.nlm.nih.gov/pubmed/28077252", "http://www.ncbi.nlm.nih.gov/pubmed/27898430", "http://www.ncbi.nlm.nih.gov/pubmed/25142767", "http://www.ncbi.nlm.nih.gov/pubmed/28365841", "http://www.ncbi.nlm.nih.gov/pubmed/27938922", "http://www.ncbi.nlm.nih.gov/pubmed/28040430" ], "ideal_answer": [ "Stop-Bang questionnaire is used to predict risk of obstructive sleep apnea (OSA)." ], "exact_answer": [ "obstructive sleep apnea" ], "type": "factoid", "id": "5a742d620384be9551000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "STUDY OBJECTIVE: The aim of this study is to evaluate whether adding the item of \"apple body type\" to the STOP-BANG questionnaire enhances diagnostic performance of the questionnaire for detecting obstructive sleep apnea (OSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28077252", "endSection": "abstract" }, { "offsetInBeginSection": 1708, "offsetInEndSection": 1910, "text": "CONCLUSION: In the sleep center setting, adding the body type item to the STOP-BANG questionnaire improves not only clinical prediction for PSG confirmed OSA but also predicts moderate to severe of OSA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28077252", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 474, "text": " High and low probability of OSA were defined as a STOP-Bang score of \u22655 (h-OSA) and of<5 (l-OSA), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28040430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The STOP-BANG questionnaire improves the detection of epilepsy patients at risk for obstructive sleep apnea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27886561", "endSection": "title" }, { "offsetInBeginSection": 119, "offsetInEndSection": 271, "text": "We performed a quality improvement project, evaluating for improvements in the screening of OSA in epilepsy patients using the STOP-BANG questionnaire. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27886561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Diagnostic accuracy of the Berlin questionnaire, STOP-BANG, STOP, and Epworth sleepiness scale in detecting obstructive sleep apnea: A bivariate meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27919588", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 371, "text": "Although screening tools such as the Berlin questionnaire (BQ), STOP-BANG questionnaire (SBQ), STOP questionnaire (STOP), and Epworth sleepiness scale (ESS) are widely used for OSA, the findings regarding their diagnostic accuracy are controversial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27919588", "endSection": "abstract" }, { "offsetInBeginSection": 2662, "offsetInEndSection": 2980, "text": "Compared with the BQ, STOP, and ESS, the SBQ is a more accurate tool for detecting mild, moderate, and severe OSA. Sleep specialists should use the SBQ to conduct patient interviews for the early diagnosis of OSA in clinical settings, particularly in resource-poor countries and sleep clinics where PSG is unavailable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27919588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Modified Mallampati Score Improves Specificity of STOP-BANG Questionnaire for Obstructive Sleep Apnea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28207464", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "BACKGROUND: An accurate, clinical screening tool for obstructive sleep apnea (OSA) that identifies patients for further diagnostic testing would assist in the diagnosis of this comorbidity. One example, the STOP-BANG questionnaire (SBQ), has been validated as a screening tool with high sensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28207464", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 824, "text": "The validated Berlin, STOP-BANG, and Epworth Sleepiness Scale questionnaires were administered to all eligible subjects to assess SA risk and daytime somnolence, and their demographic and clinical information, health-related quality of life, and symptoms of depression were collected using the questionnaires.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28283367", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1193, "text": "Ninety-nine (49.5%) subjects were identified as high risk for SA using the Berlin questionnaire, whereas 26 (13%), 137 (68.5%), and 37 (18.5%) subjects were classified as low, intermediate, and high risk for SA, respectively, using the STOP-BANG questionnaire. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28283367", "endSection": "abstract" }, { "offsetInBeginSection": 1526, "offsetInEndSection": 1707, "text": "CONCLUSIONS: The SACS and the STOP-Bang questionnaires (BMI threshold of 25\u00a0kg/m2) were found to provide the best positive and negative LRs, respectively, for the prediction of OSA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28365841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "The aims of this study were to (1) explore the incidence of right-sided heart dysfunction (RHD) and STOP-Bang questionnaire responses consistent with obstructive sleep apnea (OSA) and (2) assess the relationship between patients with STOP-Bang questionnaire responses consistent with OSA and echocardiographic findings suggestive of RHD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26547116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "This study aims: (1) to identify patients with multiple sclerosis (MS) who are at high risk for obstructive sleep apnea (OSA) by utilizing the STOP-BANG questionnaire and (2) to evaluate the relationship between OSA risk as determined by the STOP-BANG questionnaire and self-reported sleepiness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Validation of the STOP-Bang Questionnaire as a Screening Tool for Obstructive Sleep Apnea among Different Populations: A Systematic Review and Meta-Analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26658438", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Validation of a Portuguese version of the STOP-Bang questionnaire as a screening tool for obstructive sleep apnea: Analysis in a sleep clinic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25926368", "endSection": "title" }, { "offsetInBeginSection": 1856, "offsetInEndSection": 2001, "text": "This meta-analysis confirms the high performance of the STOP-Bang questionnaire in the sleep clinic and surgical population for screening of OSA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26658438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "PURPOSE OF REVIEW: The present review aims to provide an update on the various practical applications of the STOP-Bang questionnaire in anesthesia, surgery, and perioperative medicine.
RECENT FINDINGS: The STOP-Bang questionnaire was originally validated as a screening tool to identify surgical patients who are at high-risk of obstructive sleep apnea (OSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898430", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 598, "text": "Patients with a STOP-Bang score of 0--2 can be classified as low-risk for moderate-to-severe OSA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898430", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1086, "text": "Further, patients with a STOP-Bang score at least 3 can be classified as high risk for moderate-to-severe OSA if the serum HCO3 at least 28\u200ammol/l.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898430", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1371, "text": "STOP-Bang can be used as a novel tool for perioperative risk stratification because it easily identifies patients who are at increased risk of perioperative complications.
SUMMARY: STOP-Bang at least 3 was recommended previously to identify the suspected or undiagnosed OSA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898430", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1671, "text": "Because of its practical application, STOP-Bang is a useful screening tool for patients with suspected or undiagnosed OSA.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898430", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 243, "text": "The STOP-BANG questionnaire has been used to identify surgical patients at risk for undiagnosed obstructive sleep apnea (OSA) by classifying patients as low risk (LR) if STOP-BANG score < 3 or high risk (HR) if STOP-BANG score \u2265 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27610133", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 665, "text": "Among the questionnaires that are commonly used for obstructive sleep apnoea screening, it remains unclear whether the STOP-BANG or Berlin Obstructive Sleep Apnoea Syndrome questionnaire is more effective in terms of ease of use, usage period and diagnosis of surgical patients with obstructive sleep apnoea risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26961117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Evaluation of the Arabic version of STOP-Bang questionnaire as a screening tool for obstructive sleep apnea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25758298", "endSection": "title" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1403, "text": "The STOP-BANG questionnaire offers clinicians an efficient and objective tool for improving detection of OSA risk in MS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Alternative scoring models of STOP-bang questionnaire improve specificity to detect undiagnosed obstructive sleep apnea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25142767", "endSection": "title" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1716, "text": "The Arabic version of STOP-Bang questionnaire is an easy-to-use tool that can be implemented as a reliable, quick screening tool for OSA in patients referred to sleep clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25758298", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 408, "text": "This study aims: (1) to identify patients with multiple sclerosis (MS) who are at high risk for obstructive sleep apnea (OSA) by utilizing the STOP-BANG questionnaire and (2) to evaluate the relationship between OSA risk as determined by the STOP-BANG questionnaire and self-reported sleepiness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270686", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 224, "text": "This study aimed to compare the efficiency of the STOP-BANG and Berlin Obstructive Sleep Apnoea Syndrome questionnaires for evaluating potential respiratory complications during the perioperative period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26961117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "OBJECTIVE The STOP-Bang questionnaire was developed as a quick and simple screening tool for obstructive sleep apnea (OSA) in preoperative clinics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27938922", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 485, "text": "This study aimed to evaluate and validate the Arabic version of Stop-Bang questionnaire as a screening tool for patients with OSA symptoms referred to a sleep clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25758298", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 899, "text": "RESULTS Eighty-three out of 200 patients had a high risk of OSA based on the STOP-Bang questionnaire.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25010615", "endSection": "abstract" }, { "offsetInBeginSection": 1550, "offsetInEndSection": 1735, "text": "CONCLUSION The Arabic version of STOP-Bang questionnaire is an easy-to-use tool that can be implemented as a reliable, quick screening tool for OSA in patients referred to sleep clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25758298", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 359, "text": "RECENT FINDINGS The STOP-Bang questionnaire was originally validated as a screening tool to identify surgical patients who are at high-risk of obstructive sleep apnea (OSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898430", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 284, "text": "We aimed to evaluate the validity of the STOP-Bang questionnaire to predict moderate-to-severe and severe OSA in the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27938922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "STUDY OBJECTIVE To determine if a high score (\u2265 3) on the STOP-Bang screening questionnaire for obstructive sleep apnea (OSA) predicts whether obese patients are at high risk for OSA and increased risk of difficult airway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25081584", "endSection": "abstract" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1561, "text": "CONCLUSION The STOP-Bang questionnaire can be used as a screening tool in the general population in view of its moderate sensitivity and high negative predictive value for subjects with moderate-to-severe and severe OSA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27938922", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 1050, "text": "Subjects completed a questionnaire evaluating the presence and severity of AR and the STOP-BANG questionnaire (snoring, tiredness during daytime, observed apnea, high blood pressure, body mass index, age, neck circumference, gender), a validated screening method to identify obstructive sleep apnea syndrome risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24917451", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 245, "text": "The STOP-BANG questionnaire has been used to identify surgical patients at risk for undiagnosed obstructive sleep apnea (OSA) by classifying patients as low risk (LR) if STOP-BANG score < 3 or high risk (HR) if STOP-BANG score \u2265 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27610133", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1424, "text": "The STOP-BANG questionnaire offers clinicians an efficient and objective tool for improving detection of OSA risk in MS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 407, "text": "PURPOSE This study aims: (1) to identify patients with multiple sclerosis (MS) who are at high risk for obstructive sleep apnea (OSA) by utilizing the STOP-BANG questionnaire and (2) to evaluate the relationship between OSA risk as determined by the STOP-BANG questionnaire and self-reported sleepiness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270686", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1294, "text": "CONCLUSIONS Over 40% of MS patients were identified as high risk for OSA based on the STOP-BANG questionnaire.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270686", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1545, "text": "The high-risk group patients identified by STOP-BANG had significantly higher respiratory disturbance index and lower minimum oxygen saturation than the low-risk group patients.
CONCLUSION: Among the four questionnaires studied, STOP-BANG, with only eight questions and the highest sensitivity, is the best questionnaire of the four for OSA screening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "BACKGROUND: The present study validates and evaluates the sensitivity and specificity of four internationally popular questionnaires, translated into Chinese, for assessing suspected obstructive sleep apnea (OSA) patients, namely, the Berlin questionnaire, the ASA checklist, the STOP questionnaire and the STOP-BANG questionnaire.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25182345", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 503, "text": "We hypothesized that the STOP-Bang questionnaire, a screening tool for obstructive sleep apnea (OSA), can predict difficult intubation.
PATIENTS AND METHODS: In this prospective cohort study, 200 adult surgical patients undergoing surgery under general anesthesia were studied to evaluate the usefulness of the STOP-Bang questionnaire for predicting difficult intubation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25010615", "endSection": "abstract" } ] }, { "body": "List indications for palivizumab for treatment of RSV-induced bronchiolitis. ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27432850", "http://www.ncbi.nlm.nih.gov/pubmed/28813765", "http://www.ncbi.nlm.nih.gov/pubmed/24171820", "http://www.ncbi.nlm.nih.gov/pubmed/27034777", "http://www.ncbi.nlm.nih.gov/pubmed/26508190", "http://www.ncbi.nlm.nih.gov/pubmed/19811111", "http://www.ncbi.nlm.nih.gov/pubmed/19651385", "http://www.ncbi.nlm.nih.gov/pubmed/26808981", "http://www.ncbi.nlm.nih.gov/pubmed/25534557", "http://www.ncbi.nlm.nih.gov/pubmed/28084708", "http://www.ncbi.nlm.nih.gov/pubmed/28539438", "http://www.ncbi.nlm.nih.gov/pubmed/28273842", "http://www.ncbi.nlm.nih.gov/pubmed/27553073" ], "ideal_answer": [ "According to guidelines palivizumab is available for treatment of RSV-induced bronchiolitis in high-risk infants: born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease. Palivizumab reduces the burden of bronchiolitis but does not prevent infection." ], "exact_answer": [ [ "infants born before 29 weeks' gestation" ], [ "infants with chronic lung disease of prematurity" ], [ "infants and children with hemodynamically significant heart disease" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001988", "http://www.disease-ontology.org/api/metadata/DOID:2942", "http://www.disease-ontology.org/api/metadata/DOID:10007", "http://www.biosemantics.org/jochem#4241977", "https://meshb.nlm.nih.gov/record/ui?ui=D000069455" ], "type": "list", "id": "5a67a207b750ff4455000008", "snippets": [ { "offsetInBeginSection": 318, "offsetInEndSection": 398, "text": " Palivizumab reduces the burden of bronchiolitis but does not prevent infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27553073", "endSection": "abstract" }, { "offsetInBeginSection": 1541, "offsetInEndSection": 1919, "text": "Children at risk of severe lower respiratory tract infection should receive immunoprophylaxis with palivizumab, a humanized monoclonal antibody, in up to five monthly doses. Prophylaxis guidelines are restricted to infants born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28084708", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1031, "text": "Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28273842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the respiratory syncytial virus (RSV) F glycoprotein, is the only prophylactic agent approved for use for the treatment of RSV infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28539438", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 839, "text": "Palivizumab prophylaxis is recommended for infants with qualifying high risk conditions. Recent evidence-based clinical practice guidelines have been published by the American Academy of Pediatrics to guide diagnosis, treatment, and prevention of bronchiolitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28813765", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 279, "text": "Palivizumab is effective in reducing RSV hospitalization in high risk patient groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26808981", "endSection": "abstract" }, { "offsetInBeginSection": 1751, "offsetInEndSection": 1855, "text": ".CONCLUSION: Palivizumab was effective in reducing RSV-related hospitalization infection in CF patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26808981", "endSection": "abstract" }, { "offsetInBeginSection": 1480, "offsetInEndSection": 1694, "text": "CONCLUSIONS: Among infants 29 to 32 weeks' gestation without chronic illness, palivizumab use was associated with reduced RSV hospitalizations but increased hospitalizations for bronchiolitis without RSV diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432850", "endSection": "abstract" }, { "offsetInBeginSection": 1393, "offsetInEndSection": 1670, "text": "There is currently no licensed vaccine to prevent RSV infection but passive immunoprophylaxis using a monoclonal antibody, palivizumab, reduces the risk of hospitalization due to RSV infection by 39-78% in various high-risk infants predisposed to developing severe RSV disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27034777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Eligibility for palivizumab prophylaxis in a cohort of children with severe bronchiolitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508190", "endSection": "title" }, { "offsetInBeginSection": 1, "offsetInEndSection": 472, "text": "n 2014, the American Academy of Pediatrics (AAP) updated their recommendations for palivizumab prophylaxis for children who are at high risk for severe respiratory syncytial virus (RSV) infection. To investigate the potential impact of the more restrictive 2014 criteria on the eligibility for palivizumab prophylaxis, we applied the 2012 and 2014 AAP recommendations for palivizumab prophylaxis to a multicenter cohort of 2207 US children hospitalized for bronchiolitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508190", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 833, "text": "The decrease was largely driven by the restriction of eligibility to preterm infants with gestational age<29 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26508190", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 746, "text": "To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Preventing RSV bronchiolitis in vulnerable infants: the role of palivizumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19651385", "endSection": "title" }, { "offsetInBeginSection": 663, "offsetInEndSection": 824, "text": "Palivizumab a humanized monoclonal antibody directed against the F protein of RSV is the only agent licensed to prevent severe RSV disease in high-risk children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "OBJECTIVES Palivizumab, a humanized monoclonal antibody directed against respiratory syncytial virus (RSV), is the only existent immunoprophylaxis therapy for prevention of serious lower respiratory tract disease caused by RSV in infants (up to 2\u00a0years of age), particularly in those who meet high-risk criteria (preterm infants and/or those with bronchopulmonary or congenital heart disease).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534557", "endSection": "abstract" }, { "offsetInBeginSection": 2044, "offsetInEndSection": 2136, "text": "CONCLUSION Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811111", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 769, "text": "OBJECTIVE To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811111", "endSection": "abstract" } ] }, { "body": "List factors that promote lymphangiogenesis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28087639", "http://www.ncbi.nlm.nih.gov/pubmed/28228406", "http://www.ncbi.nlm.nih.gov/pubmed/27527525", "http://www.ncbi.nlm.nih.gov/pubmed/27787629", "http://www.ncbi.nlm.nih.gov/pubmed/28723974" ], "ideal_answer": [ "VEGF-C\nVEGF-D\nVEGF-R3" ], "exact_answer": [ [ "VEGF-C" ], [ "VEGF-D" ], [ "VEGF-R3" ] ], "type": "list", "id": "5a89a20ffcd1d6a10c00000e", "snippets": [ { "offsetInBeginSection": 101, "offsetInEndSection": 271, "text": "Lymphangiogenesis plays an important role in cancer progression and is regulated by a complex mechanism that includes vascular endothelial growth factor (VEGF) signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27527525", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1733, "text": "ur results demonstrate that NHT stimulates lymphangiogenesis via upregulation of VEGF-C and -D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27527525", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 328, "text": "Vegfc is essential for secondary angiogenesis, giving rise to veins and lymphatics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28087639", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 755, "text": "vegfc and vegfd cooperatively control lymphangiogenesis throughout the embryo, including during the formation of the trunk lymphatic vasculature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28087639", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 889, "text": "The signals for lymphangiogenesis, VEGF-C and its receptor VEGF-R3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28228406", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 430, "text": "Vascular endothelial growth factor (VEGF) members VEGF-C and VEGF-D are both potent candidates for stimulating lymphangiogenesis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28723974", "endSection": "abstract" } ] }, { "body": "Which siRNA based drug is in clinical trials for the treatment of pancreatic cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26009994", "http://www.ncbi.nlm.nih.gov/pubmed/27147553" ], "ideal_answer": [ "siG12D-LODERTM has been tested in a phase 1/2a clinical trial of patients with pancreatic cancer.", "siG12D-LODER\u2122" ], "exact_answer": [ "siG12D-LODERTM" ], "type": "factoid", "id": "5a74a8a70384be9551000005", "snippets": [ { "offsetInBeginSection": 1308, "offsetInEndSection": 1442, "text": "The combination of siG12D-LODER\u2122 and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009994", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 548, "text": "An open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009994", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 290, "text": "The miniature biodegradable implant siG12D-LODER\u2122 was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009994", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 289, "text": "The miniature biodegradable implant siG12D-LODER\u2122 was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 435, "text": "Conventional chemotherapy treatments for pancreatic cancer are mainly palliative. RNA interference (RNAi)-based drugs present the potential for a new targeted treatment. LOcal Drug EluteR (LODER(TM)) is a novel biodegradable polymeric matrix that shields drugs against enzymatic degradation and releases small interfering RNA (siRNA) against G12D-mutated KRAS (siG12D). siG12D-LODER has successfully passed a phase 1/2a clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27147553", "endSection": "abstract" } ] }, { "body": "How is CTCF activated post-translationally?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19170077", "http://www.ncbi.nlm.nih.gov/pubmed/22969794", "http://www.ncbi.nlm.nih.gov/pubmed/18539602", "http://www.ncbi.nlm.nih.gov/pubmed/15361875" ], "ideal_answer": [ "The chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation.", "Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation. the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation Chromatin immunoprecipitation-on-chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. ", "Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation." ], "type": "summary", "id": "5a86ea05faa1ab7d2e000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361875", "endSection": "title" }, { "offsetInBeginSection": 148, "offsetInEndSection": 251, "text": " the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361875", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 679, "text": "Chromatin immunoprecipitation-on-chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361875", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1093, "text": "poly(ADP-ribosyl)ation imparts chromatin insulator properties to CTCF at both imprinted and nonimprinted loci, which has implications for the regulation of expression domains and their demise in pathological lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361875", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 309, "text": "The very rapid and transient post-translational modification of proteins by poly(ADP-ribose) has been shown to take part in all four.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22969794", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1298, "text": "This review will discuss the impact of PARP1 on transcription and transcription factors, its implication in chromatin remodeling for DNA repair and probably also replication, and its role in controlling epigenetic events such as DNA methylation and the functionality of the insulator protein CCCTC-binding factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22969794", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1442, "text": "These data suggest that CTCF is involved in the cross-talk between poly(ADP-ribosyl)ation and DNA methylation and underscore the importance of a rapid reversal of PARP activity, as DNA methylation pattern is responsible for an important epigenetic code.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18539602", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 252, "text": "We show that the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361875", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 515, "text": "Chromatin immunoprecipitation analysis showed that a poly(ADP-ribosyl)ation mark, which exclusively segregates with the maternal allele of the insulator domain in the H19 imprinting control region, requires the bases that are essential for interaction with CTCF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1082, "text": "chromatin insulators demarcate expression domains by blocking the cis effects of enhancers or silencers in a position dependent manner we show that the chromatin insulator protein ctcf carries a post translational modification poly adp ribosyl ation chromatin immunoprecipitation analysis showed that a poly adp ribosyl ation mark which exclusively segregates with the maternal allele of the insulator domain in the h19 imprinting control region requires the bases that are essential for interaction with ctcf chromatin immunoprecipitation on chip analysis documented that the link between ctcf and poly adp ribosyl ation extended to more than 140 mouse ctcf target sites an insulator trap assay showed that the insulator function of most of these ctcf target sites is sensitive to 3 aminobenzamide an inhibitor of poly adp ribose polymerase activity we suggest that poly adp ribosyl ation imparts chromatin insulator properties to ctcf at both imprinted and nonimprinted loci which has implications for the regulation of expression domains and their demise in pathological lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 924, "text": "ccctc binding factor ctcf is a ubiquitous zn finger containing protein with numerous recognized functions including but not limited to gene activation and repression enhancer blocking x chromosome inactivation and gene imprinting it is believed that the protein performs such a variety of functions by interacting with an array of very diverse proteins in addition ctcf undergoes several post translational modifications including poly adp ribosyl ation the parylated form of ctcf has recently been implicated in two important functions gene imprinting and control of ribosomal gene transcription here we summarize and critically discuss the available data on the interplay between ctcf and poly adp ribosyl ation in these two processes we consider the newly described phenomena in the broader context of parp s activities including the crucial role of protein parylation in the regulation of the genome methylation pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19170077", "endSection": "abstract" } ] }, { "body": "What is the HPG pore?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26921234" ], "ideal_answer": [ "The use of nanopore technologies is expected to spread in the future because they are portable and can sequence long fragments of DNA molecules without prior amplification. The first nanopore sequencer available, the MinION\u2122 from Oxford Nanopore Technologies, is a USB-connected, portable device that allows real-time DNA analysis. In addition, other new instruments are expected to be released soon, which promise to outperform the current short-read technologies in terms of throughput. Despite the flood of data expected from this technology, the data analysis solutions currently available are only designed to manage small projects and are not scalable. HPG pore is a toolkit for exploring and analysing nanopore sequencing data. HPG Pore can run on both individual computers and in the Hadoop distributed computing framework, which allows easy scale-up to manage the large amounts of data expected to result from extensive use of nanopore technologies in the future." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D020411", "https://meshb.nlm.nih.gov/record/ui?ui=D017422" ], "type": "summary", "id": "5a80a63ffaa1ab7d2e000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "HPG pore: an efficient and scalable framework for nanopore sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921234", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1006, "text": "The use of nanopore technologies is expected to spread in the future because they are portable and can sequence long fragments of DNA molecules without prior amplification. The first nanopore sequencer available, the MinION\u2122 from Oxford Nanopore Technologies, is a USB-connected, portable device that allows real-time DNA analysis. In addition, other new instruments are expected to be released soon, which promise to outperform the current short-read technologies in terms of throughput. Despite the flood of data expected from this technology, the data analysis solutions currently available are only designed to manage small projects and are not scalable.RESULTS: Here we present HPG Pore, a toolkit for exploring and analysing nanopore sequencing data. HPG Pore can run on both individual computers and in the Hadoop distributed computing framework, which allows easy scale-up to manage the large amounts of data expected to result from extensive use of nanopore technologies in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921234", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 748, "text": "Here we present HPG Pore, a toolkit for exploring and analysing nanopore sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921234", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 786, "text": "Despite the flood of data expected from this technology, the data analysis solutions currently available are only designed to manage small projects and are not scalable.
RESULTS: Here we present HPG Pore, a toolkit for exploring and analysing nanopore sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921234", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 771, "text": "RESULTS Here we present HPG Pore, a toolkit for exploring and analysing nanopore sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1175, "text": "the use of nanopore technologies is expected to spread in the future because they are portable and can sequence long fragments of dna molecules without prior amplification the first nanopore sequencer available the minion from oxford nanopore technologies is a usb connected portable device that allows real time dna analysis in addition other new instruments are expected to be released soon which promise to outperform the current short read technologies in terms of throughput despite the flood of data expected from this technology the data analysis solutions currently available are only designed to manage small projects and are not scalable here we present hpg pore a toolkit for exploring and analysing nanopore sequencing data hpg pore can run on both individual computers and in the hadoop distributed computing framework which allows easy scale up to manage the large amounts of data expected to result from extensive use of nanopore technologies in the future hpg pore allows for virtually unlimited sequencing data scalability thus guaranteeing its continued management in near future scenarios hpg pore is available in github at http github com opencb hpg pore.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "hpg pore an efficient and scalable framework for nanopore sequencing data", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26921234", "endSection": "title" } ] }, { "body": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/5470040", "http://www.ncbi.nlm.nih.gov/pubmed/15803962", "http://www.ncbi.nlm.nih.gov/pubmed/589307", "http://www.ncbi.nlm.nih.gov/pubmed/21375200", "http://www.ncbi.nlm.nih.gov/pubmed/17880731" ], "ideal_answer": [ "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT),", "Aspartate transaminase or aspartate aminotransferase, also known as AspAT/ASAT/AAT/AST is also known as serum glutamic oxaloacetic transaminase SGOT", "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), aspartate aminotransferase (AST-SGOT), alanine amino-transferase (ALT-SGPT)", "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), Alanine amino transferase (SGPT), " ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004798" ], "type": "yesno", "id": "5a67b48cb750ff4455000010", "snippets": [ { "offsetInBeginSection": 433, "offsetInEndSection": 516, "text": "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21375200", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 410, "text": "Alanine amino transferase (SGPT), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17880731", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 549, "text": "aspartate aminotransferase (AST-SGOT), alanine amino-transferase (ALT-SGPT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15803962", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 550, "text": "Mean values of glutamate dehydrogenase (GDH), serum aspartate and alanine transferase (SGOT and SGPT), ornithine carbamoyltransferase (OCT), and gamma-glutamyltranspeptidase (gamma-GTP) tended to rise with increasing liver cell necrosis, though values of SGOT, SGPT, OCT, and gamma-GTP showed considerable overlap between the 32 patients with histologically proved hepatitis and the 68 without.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/589307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Serum aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), creatinine phosphokinase (CPK), and butyric acid dehydrogenase (BDH) were determined in 94 patients before, 1(1/2) hours, and 24 hours after cardioversion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/5470040", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 627, "text": "The study excluded by screening for AntiHCV, HBsAg and patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), GGT levels more than three times the normal and subject with a total leukocyte count more than 10,000/microl.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21375200", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 488, "text": "Complete blood picture, differential leukocyte count, and serum levels of Estrogen, Alanine amino transferase (SGPT), Aspartate amino transferase (SGOT), total protein and albumin were estimated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17880731", "endSection": "abstract" } ] }, { "body": "Is patisiran currently (November 2017) in clinical phase II trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26338094", "http://www.ncbi.nlm.nih.gov/pubmed/28389707", "http://www.ncbi.nlm.nih.gov/pubmed/28893208" ], "ideal_answer": [ "No, patisiran is in phase 3 clinical studies.", "No, patisiran is in clinical phase 3 trials" ], "exact_answer": "no", "type": "yesno", "id": "5a735c143b9d13c708000003", "snippets": [ { "offsetInBeginSection": 435, "offsetInEndSection": 728, "text": "This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials. The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389707", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 726, "text": " patisiran (phase 3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389707", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 484, "text": " Phase 3 APOLLO study, a randomized, double-blind, placebo-controlled, global study to evaluate the efficacy and safety of patisiran in patients with hATTR amyloidosis with polyneuropathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28893208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26338094", "endSection": "title" } ] }, { "body": "Which R/Bioconductor package has been developed for cancer subtype identification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28605519" ], "ideal_answer": [ "Identifying molecular cancer subtypes from multi-omics data is an important step in the personalized medicine. CancerSubtypes is an R/Bioconductor package for molecular cancer subtype identification, validation and visualization. CancerSubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre-processing, feature selection, and result follow-up analyses, including results computing, biology validation and visualization. The input and output of each step in the framework are packaged in the same data format, making it convenience to compare different methods." ], "exact_answer": [ "CancerSubtypes" ], "type": "factoid", "id": "5a6e3155b750ff445500003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "CancerSubtypes: an R/Bioconductor package for molecular cancer subtype identification, validation and visualization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 986, "text": "Identifying molecular cancer subtypes from multi-omics data is an important step in the personalized medicine. We introduce CancerSubtypes, an R package for identifying cancer subtypes using multi-omics data, including gene expression, miRNA expression and DNA methylation data. CancerSubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre-processing, feature selection, and result follow-up analyses, including results computing, biology validation and visualization. The input and output of each step in the framework are packaged in the same data format, making it convenience to compare different methods. The package is useful for inferring cancer subtypes from an input genomic dataset, comparing the predictions from different well-known methods and testing new subtype discovery methods, as shown with different application scenarios in the Supplementary Material.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 573, "text": "CancerSubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre-processing, feature selection, and result follow-up analyses, including results computing, biology validation and visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 278, "text": "We introduce CancerSubtypes, an R package for identifying cancer subtypes using multi-omics data, including gene expression, miRNA expression and DNA methylation data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 294, "text": "We introduce CancerSubtypes, an R package for identifying cancer subtypes using multi-omics data, including gene expression, miRNA expression and DNA methylation data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 589, "text": "CancerSubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre-processing, feature selection, and result follow-up analyses, including results computing, biology validation and visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 286, "text": "We introduce CancerSubtypes, an R package for identifying cancer subtypes using multi-omics data, including gene expression, miRNA expression and DNA methylation data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 581, "text": "CancerSubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre-processing, feature selection, and result follow-up analyses, including results computing, biology validation and visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "cancersubtypes an r bioconductor package for molecular cancer subtype identification validation and visualization", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1211, "text": "identifying molecular cancer subtypes from multi omics data is an important step in the personalized medicine we introduce cancersubtypes an r package for identifying cancer subtypes using multi omics data including gene expression mirna expression and dna methylation data cancersubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre processing feature selection and result follow up analyses including results computing biology validation and visualization the input and output of each step in the framework are packaged in the same data format making it convenience to compare different methods the package is useful for inferring cancer subtypes from an input genomic dataset comparing the predictions from different well known methods and testing new subtype discovery methods as shown with different application scenarios in the supplementary material the package is implemented in r and available under gpl 2 license from the bioconductor website http bioconductor org packages cancersubtypes thuc le unisa edu au or jiuyong li unisa edu au supplementary data are available at bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605519", "endSection": "abstract" } ] }, { "body": "Is Solanezumab effective for Alzheimer's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29067346", "http://www.ncbi.nlm.nih.gov/pubmed/26238576", "http://www.ncbi.nlm.nih.gov/pubmed/28593105", "http://www.ncbi.nlm.nih.gov/pubmed/28649604", "http://www.ncbi.nlm.nih.gov/pubmed/24450890", "http://www.ncbi.nlm.nih.gov/pubmed/26990863", "http://www.ncbi.nlm.nih.gov/pubmed/26815584", "http://www.ncbi.nlm.nih.gov/pubmed/27223100", "http://www.ncbi.nlm.nih.gov/pubmed/27239541" ], "ideal_answer": [ "No. Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability in patients with Alzheimer's Disease." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000544", "http://www.disease-ontology.org/api/metadata/DOID:10652" ], "type": "yesno", "id": "5a70e1d999e2c3af26000007", "snippets": [ { "offsetInBeginSection": 465, "offsetInEndSection": 704, "text": "An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29067346", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 783, "text": "Notably, a recent study of solanezumab, an amyloid \u03b2 monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer's disease, but also for other neurodegenerative disorders, including Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28649604", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 734, "text": "For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28593105", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 738, "text": "Areas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27223100", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 441, "text": " Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26815584", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 869, "text": "Secondary analyses of EXPEDITION studies suggested a smaller functional effect of solanezumab relative to cognition. An increasing effect of solanezumab over 18\u00a0months was shown for cognition and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27239541", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 862, "text": "RESULTS: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n\u00a0=\u00a0659) versus placebo (n\u00a0=\u00a0663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale Instrumental ADLs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26238576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "The promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26990863", "endSection": "abstract" }, { "offsetInBeginSection": 2247, "offsetInEndSection": 2376, "text": "CONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24450890", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 298, "text": "Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26815584", "endSection": "abstract" } ] }, { "body": "Are organisms in the genus Morexella associated with sepsis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24669633" ], "ideal_answer": [ "Moraxella species may cause neonatal sepsis" ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000071074", "https://meshb.nlm.nih.gov/record/ui?ui=D018805" ], "type": "yesno", "id": "5a679be1b750ff4455000005", "snippets": [ { "offsetInBeginSection": 889, "offsetInEndSection": 1390, "text": "Out of 130 culture proven cases of neonatal sepsis, gram negative bacteria were found in 71 (54.6%) cases and gram positive bacteria in 59 (45.4%) cases. Staphylococcus aureus was the most common bacteria found in 35 (26.9%) cases followed by Escherichia coli in 30 (23.1%) cases. Acinetobacter species, Staphylococcus epidermidis, Klebseila, Streptococci, Enterobacter cloacae and Morexella species were found in 17 (13.1%), 17 (13.1%), 13 (10%), 7 (5.4%), 6 (4.6%), and 5 (3.8%) cases respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24669633", "endSection": "abstract" } ] }, { "body": "Are there mammalian promoters with distal enhancer functions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28581502" ], "ideal_answer": [ "Yes. Several studies have suggested that some promoters might have enhancer functions. By exploiting a high-throughput enhancer reporter assay, scientists have unraveled a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0001206", "http://amigo.geneontology.org/amigo/term/GO:0001205", "http://amigo.geneontology.org/amigo/term/GO:0035326", "https://meshb.nlm.nih.gov/record/ui?ui=D011401", "http://amigo.geneontology.org/amigo/term/GO:0003705", "http://amigo.geneontology.org/amigo/term/GO:0071733", "https://meshb.nlm.nih.gov/record/ui?ui=D004742" ], "type": "yesno", "id": "5a6fabfeb750ff4455000062", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Genome-wide characterization of mammalian promoters with distal enhancer functions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28581502", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 902, "text": "Gene expression in mammals is precisely regulated by the combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might have enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28581502", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 499, "text": "Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28581502", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 219, "text": "Several studies have suggested that some promoters might have enhancer functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28581502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "genome wide characterization of mammalian promoters with distal enhancer functions", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28581502", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 892, "text": "gene expression in mammals is precisely regulated by the combination of promoters and gene distal regulatory regions known as enhancers several studies have suggested that some promoters might have enhancer functions however the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive here by exploiting a high throughput enhancer reporter assay we unravel a set of mammalian promoters displaying enhancer activity these promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters extensive crispr cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci our results have important implications for the understanding of complex gene regulation in normal development and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28581502", "endSection": "abstract" } ] }, { "body": "What gene is mutated in Familial Mediterranean Fever?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21358337", "http://www.ncbi.nlm.nih.gov/pubmed/28040706", "http://www.ncbi.nlm.nih.gov/pubmed/18219832", "http://www.ncbi.nlm.nih.gov/pubmed/24702757", "http://www.ncbi.nlm.nih.gov/pubmed/23844200", "http://www.ncbi.nlm.nih.gov/pubmed/14636645", "http://www.ncbi.nlm.nih.gov/pubmed/16283319", "http://www.ncbi.nlm.nih.gov/pubmed/22057232", "http://www.ncbi.nlm.nih.gov/pubmed/26042122", "http://www.ncbi.nlm.nih.gov/pubmed/12387810", "http://www.ncbi.nlm.nih.gov/pubmed/12966608", "http://www.ncbi.nlm.nih.gov/pubmed/22614345", "http://www.ncbi.nlm.nih.gov/pubmed/10666224", "http://www.ncbi.nlm.nih.gov/pubmed/15720243", "http://www.ncbi.nlm.nih.gov/pubmed/23505242", "http://www.ncbi.nlm.nih.gov/pubmed/9758573", "http://www.ncbi.nlm.nih.gov/pubmed/28624931", "http://www.ncbi.nlm.nih.gov/pubmed/24318677", "http://www.ncbi.nlm.nih.gov/pubmed/28690860", "http://www.ncbi.nlm.nih.gov/pubmed/20437121", "http://www.ncbi.nlm.nih.gov/pubmed/25393764", "http://www.ncbi.nlm.nih.gov/pubmed/24980720", "http://www.ncbi.nlm.nih.gov/pubmed/15529356" ], "ideal_answer": [ "The MEFV gene which encodes the pyrin protein is mutated in Familial Mediterranean Fever(FMF)." ], "exact_answer": [ "MEFV gene" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D028226", "http://www.disease-ontology.org/api/metadata/DOID:2987", "https://meshb.nlm.nih.gov/record/ui?ui=D010505" ], "type": "factoid", "id": "5a6e42f1b750ff4455000046", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene and the spectrum of mutations among Greek-Cypriots with FMF-related symptoms was examined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25393764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome and characterized by recurrent episodes of fever, serositis, arthritis, dermal manifestations, and long-term renal complications. The MEFV gene was described in 1997 as the gene responsible for FMF and is inherited in autosomal recessive manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28624931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease that is inherited in an autosomal recessive manner and is caused by mutations in theMEFVgene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28690860", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 151, "text": " MEditerranean FeVer (MEFV) gene encodes for the pyrin protein and a mutated pyrin is associated with a prolonged or augmented inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28040706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26042122", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 213, "text": "Familial Mediterranean Fever (FMF), characterized by recurrent fever and inflammation of serous membranes, is an autosomal recessive disease caused by mutations in the Mediterranean fever (MEFV) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980720", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 217, "text": " patients affected by familial Mediterranean fever (FMF) whether or not interleukin (IL)-1\u03b2 secretion (1) is enhanced, (2) correlates with the type of MEFV mutation and (3) is mediated by NLRP3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23505242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Familial Mediterranean fever (FMF) is a recessive inherited autoinflammatory syndrome. Patients with FMF have symptoms such as recurrent fever and abdominal pain, sometimes accompanied by arthralgia. Biopsy specimens have revealed substantial neutrophil infiltration into synovia. FMF patients have a mutation in the Mediterranean fever gene, encoding pyrin,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24318677", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 280, "text": "Atherosclerosis is the main pathogenesis. Familial Mediterranean fever (FMF) is an autosomal recessive disease. The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24702757", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 181, "text": "Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder due to MEFV mutations and one of the most frequent Mediterranean genetic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23844200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The aim of this study was to determine the relationship between clinical findings and the most common mutated alleles of MEFV gene in a childhood population and to determine the sensitivity of the 12-mutation-strip assay test in familial Mediterranean fever (FMF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22057232", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 543, "text": "Familial Mediterranean fever (FMF) has been traced to mutations in the MEFV gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12387810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "BACKGROUND Familial Mediterranean Fever (FMF), characterized by recurrent fever and inflammation of serous membranes, is an autosomal recessive disease caused by mutations in the Mediterranean fever (MEFV) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980720", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 473, "text": "On the other hand, asthma is less frequent in individuals with familial Mediterranean fever, an autoinflammatory disease prevalent in the Iraqi Jewish community and linked to mutations in the familial Mediterranean fever gene, designated MEFV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18219832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "familial mediterranean fever associated with mefv mutations in a large cohort of cypriot patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25393764", "endSection": "title" }, { "offsetInBeginSection": 288, "offsetInEndSection": 350, "text": "FMF is caused by mutations in MEFV gene, which encodes pyrin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16283319", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 380, "text": "he familial Mediterranean fever gene, designated MEFV, was recently cloned, and at least three missense mutations (M6801, M694V, and V726A) that account for a large percentage of patients with this disease were identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9758573", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1317, "text": "Molecular genetic testing of the MEFV gene, the only gene currently known to be associated with familial Mediterranean fever, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21358337", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 232, "text": "To analyze 70 individuals who were found to have the Mediterranean fever (MEFV) gene for the presence of definite familial Mediterranean fever (FMF) and to assess if they were prone to clinical and laboratory inflammation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12966608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Familial Mediterranean fever is a recessive autoinflammatory disease that is frequent in Armenians, Jews, Arabs, and Turks. The MEFV gene is responsible for this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22614345", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 223, "text": "FMF is caused by mutations in the Mediterranean fever gene (MEFV),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14636645", "endSection": "abstract" } ] }, { "body": "Which R/bioconductor package has been developed to aid in epigenomic analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28334349" ], "ideal_answer": [ "DeepBlueR is a package that allows for large-scale epigenomic analysis in R.", "DeepBlueR" ], "exact_answer": [ "DeepBlueR" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D057890" ], "type": "factoid", "id": "5a6e354fb750ff4455000042", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "DeepBlueR: large-scale epigenomic analysis in R.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334349", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "deepbluer large scale epigenomic analysis in r", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334349", "endSection": "title" } ] }, { "body": "Is autosomal dominant inheritanced form of Osteogenesis imperfecta caused by mutations in the genes associated with collagen production?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27312322", "http://www.ncbi.nlm.nih.gov/pubmed/2992938", "http://www.ncbi.nlm.nih.gov/pubmed/27677223", "http://www.ncbi.nlm.nih.gov/pubmed/21567925", "http://www.ncbi.nlm.nih.gov/pubmed/22863195", "http://www.ncbi.nlm.nih.gov/pubmed/28116328", "http://www.ncbi.nlm.nih.gov/pubmed/18566967", "http://www.ncbi.nlm.nih.gov/pubmed/27510842", "http://www.ncbi.nlm.nih.gov/pubmed/21341209", "http://www.ncbi.nlm.nih.gov/pubmed/28820180", "http://www.ncbi.nlm.nih.gov/pubmed/12362985", "http://www.ncbi.nlm.nih.gov/pubmed/2886666", "http://www.ncbi.nlm.nih.gov/pubmed/24928016", "http://www.ncbi.nlm.nih.gov/pubmed/29150909", "http://www.ncbi.nlm.nih.gov/pubmed/2037280", "http://www.ncbi.nlm.nih.gov/pubmed/27762305", "http://www.ncbi.nlm.nih.gov/pubmed/21667357", "http://www.ncbi.nlm.nih.gov/pubmed/19533842", "http://www.ncbi.nlm.nih.gov/pubmed/25402547", "http://www.ncbi.nlm.nih.gov/pubmed/20839288", "http://www.ncbi.nlm.nih.gov/pubmed/8456806" ], "ideal_answer": [ "Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones. The autosomal dominant form of the disease is cause by a mutation in the COL1A1 or COL1A2 genes which produce type I collagen.", "steogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations inCOL1A1orCOL1A2and show autosomal dominant inheritance," ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4249099", "http://www.disease-ontology.org/api/metadata/DOID:0110341", "http://www.disease-ontology.org/api/metadata/DOID:0110340", "http://www.disease-ontology.org/api/metadata/DOID:0110343", "http://www.disease-ontology.org/api/metadata/DOID:0110337", "http://www.disease-ontology.org/api/metadata/DOID:0110338", "http://www.disease-ontology.org/api/metadata/DOID:0110342", "http://www.disease-ontology.org/api/metadata/DOID:0110336", "https://meshb.nlm.nih.gov/record/ui?ui=D010013", "https://meshb.nlm.nih.gov/record/ui?ui=D005799", "http://www.disease-ontology.org/api/metadata/DOID:0110334", "http://www.disease-ontology.org/api/metadata/DOID:12347", "http://www.disease-ontology.org/api/metadata/DOID:0110335" ], "type": "yesno", "id": "5a6f77d7b750ff4455000051", "snippets": [ { "offsetInBeginSection": 13, "offsetInEndSection": 222, "text": "steogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations inCOL1A1orCOL1A2and show autosomal dominant inheritance,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by decreased bone mass and increased fracture risk. The majority of OI cases have an autosomal dominant pattern of inheritance and are usually caused by mutations in genes encoding type I collagen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27762305", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 281, "text": " Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. Most OI cases follow an autosomal dominant pattern of inheritance and are attributed to mutations in genes encoding type I collagen (COL1A1/COL1A2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27312322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27677223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 385, "text": "Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal-dominant inheritance, but many autosomal-recessive genes have been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25402547", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 159, "text": "To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24928016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Dominant inheritance of osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21667357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 805, "text": "Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It exhibits a broad spectrum of clinical severity, ranging from multiple fractures in utero and perinatal death, to normal adult stature and low fracture incidence. Extra-skeletal features of OI include blue sclera, hearing loss, skin hyperlaxity, joint hyperextensibility, and dentinogenesis imperfecta. The pro\u03b11(I) and pro\u03b12(I) chains of collagen 1 are encoded by the COL1A1 and COL1A2 genes, respectively; quantitative or qualitative defects in type I collagen synthesis usually manifest as types of OI or some sub-types of EDS. The majority of patients (about 90%) with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21567925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 478, "text": "Osteogenesis imperfecta (OI) type I is characterized by bone fragility without significant deformity, osteopenia, normal stature, blue sclerae, and autosomal dominant inheritance. Dermal fibroblasts from most affected individuals produce about half the expected amount of type I collagen, suggesting that the OI type I phenotype results from a variety of mutations which alter the apparent expression of either COL1A1 or COL1A2, the genes encoding the chains of type I collagen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Autosomal dominant osteogenesis imperfecta is caused by mutations in the COL1A2 and COL1A1 genes of type I collagen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2886666", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 544, "text": "Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28820180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27510842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18566967", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 326, "text": "In approximately 90% of individuals with osteogenesis imperfecta, mutations in either of the genes encoding the pro-alpha1 or pro-alpha2 chains of type I collagen (COL1A1 or COL1A2) can be identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19533842", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 303, "text": "Autosomal dominant OI is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20839288", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 659, "text": "ext-generation sequencing technology was used to screen a panel of known OI genes.RESULTS: In 41 probands, we identified 28 different disease-causing variants of 9 different known OI genes. Eleven of the variants are novel. Ten of the 28 variants are located in COL1A1, five in COL1A2, three in BMP1, three in FKBP10, two in TMEM38B, two in P3H1, and one each in CRTAP, SERPINF1, and SERPINH1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29150909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder associated with bone fragility and susceptibility to fractures after minimal trauma. OI type V has an autosomal-dominant pattern of inheritance and is not caused by mutations in the type I collagen genes COL1A1 and COL1A2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22863195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Detection of a high frequency RsaI polymorphism in the human pro alpha 2(I) collagen gene which is linked to an autosomal dominant form of osteogenesis imperfecta.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2992938", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Osteogenesis imperfecta due to recurrent point mutations at CpG dinucleotides in the COL1A1 gene of type I collagen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2037280", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "Osteogenesis imperfecta (OI), commonly known as \"brittle bone disease\", is a dominant autosomal disorder characterized by bone fragility and abnormalities of connective tissue. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in either the COL1A1 or COL1A2 genes that encode the chains of type I procollagen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12362985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21341209", "endSection": "abstract" } ] }, { "body": "Is Apremilast effective for Behcet\u2019s syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24882690", "http://www.ncbi.nlm.nih.gov/pubmed/24797159", "http://www.ncbi.nlm.nih.gov/pubmed/26487500", "http://www.ncbi.nlm.nih.gov/pubmed/26555450", "http://www.ncbi.nlm.nih.gov/pubmed/27163156", "http://www.ncbi.nlm.nih.gov/pubmed/25875256" ], "ideal_answer": [ "Yes. Apremilast was proven to be effective for treatment of Behcet\u2019s syndrome." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D016896", "http://www.disease-ontology.org/api/metadata/DOID:13241", "https://meshb.nlm.nih.gov/record/ui?ui=D001528" ], "type": "yesno", "id": "5a7340962dc08e987e000017", "snippets": [ { "offsetInBeginSection": 613, "offsetInEndSection": 843, "text": "Apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition. A randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26555450", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 686, "text": "AREAS COVERED: This review provides a digest of all current experience and evidence about pharmacological agents recently described as having a role in the treatment of BS, including interleukin (IL)-1 inhibitors, tocilizumab, rituximab, alemtuzumab, ustekinumab, interferon-alpha-2a, and apremilast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27163156", "endSection": "abstract" }, { "offsetInBeginSection": 1719, "offsetInEndSection": 1840, "text": "CONCLUSIONS: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 1823, "offsetInEndSection": 1940, "text": " Apremilast, an inhibitor of phosphodiesterase-4, was effective in a phase 2, double blind, placebo-controlled study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26487500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Apremilast (Otezla(\u00ae)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Beh\u00e7et's syndrome, atopic dermatitis, and rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24797159", "endSection": "abstract" }, { "offsetInBeginSection": 1677, "offsetInEndSection": 1880, "text": "There were two serious adverse events in patients receiving apremilast.
CONCLUSIONS: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Apremilast (Otezla(\u00ae)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Beh\u00e7et's syndrome, atopic dermatitis, and rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24797159", "endSection": "abstract" }, { "offsetInBeginSection": 1732, "offsetInEndSection": 1853, "text": "CONCLUSIONS Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24882690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1998, "text": "oral ulcers the hallmark of beh\u00e7et s syndrome can be resistant to conventional treatment therefore alternative agents are needed apremilast is an oral phosphodiesterase 4 inhibitor that modulates several inflammatory pathways we conducted a phase 2 multicenter placebo controlled study in which 111 patients with beh\u00e7et s syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks this regimen was followed by a 12 week extension phase in which the placebo group was switched to apremilast and a 28 day post treatment observational follow up phase the patients and clinicians were unaware of the study assignments throughout the trial the primary end point was the number of oral ulcers at week 12 secondary outcomes included pain from these ulcers measured on a 100 mm visual analogue scale with higher scores indicating worse pain the number of genital ulcers overall disease activity and quality of life the mean sd number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group 0 5 1 0 vs 2 1 2 6 p 0 001 the mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo 44 7 24 3 mm vs 16 0 32 5 mm p 0 001 nausea vomiting and diarrhea were more common in the apremilast group with 22 9 and 12 incidents respectively among 55 patients than in the placebo group with 10 1 and 2 incidents respectively among 56 patients findings that were similar to those in previous studies of apremilast there were two serious adverse events in patients receiving apremilast apremilast was effective in treating oral ulcers which are the cardinal manifestation of beh\u00e7et s syndrome this preliminary study was neither large enough nor long enough to assess long term efficacy the effect on other manifestations of beh\u00e7et s syndrome or the risk of uncommon serious adverse events funded by celgene clinicaltrials gov number nct00866359.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1057, "text": "current trends in the management of beh\u00e7et s syndrome will be reviewed in this article biologic agents have gained increasing importance over the years in the management of beh\u00e7et s syndrome long term results of observational studies have shown that anti tumor necrosis factor agents may be effective in beh\u00e7et s syndrome patients with refractory eye involvement case series reporting about use of anti tumor necrosis factor agents in vascular and gastrointestinal involvement have also shown good results caution is required for infectious complications with these agents apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition a randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated the outcome of beh\u00e7et s syndrome with major organ involvement has improved with more effective management strategies especially with the use of biologic agents in severe cases controlled trials are needed to guide physicians in making treatment decisions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26555450", "endSection": "abstract" } ] }, { "body": "Are splicing speckles associated with transcription?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26496460", "http://www.ncbi.nlm.nih.gov/pubmed/12011111", "http://www.ncbi.nlm.nih.gov/pubmed/16467386", "http://www.ncbi.nlm.nih.gov/pubmed/21086038", "http://www.ncbi.nlm.nih.gov/pubmed/20514231" ], "ideal_answer": [ "Speckles contain little detectable transcriptional activity.", "yes" ], "exact_answer": "no", "type": "yesno", "id": "5a8965f6fcd1d6a10c000005", "snippets": [ { "offsetInBeginSection": 254, "offsetInEndSection": 388, "text": "We show here that RNA splicing speckled domains (splicing speckles) fluctuate in constrained nuclear volumes and remodel their shapes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26496460", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1339, "text": "We present a model where recycling splicing factors return as part of small sub-speckles from distal sites of RNA processing to larger splicing speckles by a directed ATP-driven mechanism through interchromatin spaces.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26496460", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 630, "text": "Analysis of a HeLa cell line stably expressing EYFP-NHPX showed that the nucleolar accumulation of NHPX was preceded by its transient accumulation in splicing speckles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12011111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "In vivo analysis of NHPX reveals a novel nucleolar localization pathway involving a transient accumulation in splicing speckles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12011111", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "\"Splicing speckles\" are major nuclear domains rich in components of the splicing machinery and polyA(+) RNA. Although speckles contain little detectable transcriptional activity, they are found preferentially associated with specific mRNA-coding genes and gene-rich R bands, and they accumulate some unspliced pre-mRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16467386", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 474, "text": "RNA polymerase II transcribes mRNAs and is required for splicing, with some reports suggesting that the inactive complexes are stored in splicing speckle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16467386", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 565, "text": "In normal cell growth conditions GFPeIF4A-III was mainly nucleoplasmic, but in hypoxia stress conditions it moved to the nucleolus and splicing speckles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20514231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Localization of eIF4A-III in the nucleolus and splicing speckles is an indicator of plant stress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20514231", "endSection": "title" }, { "offsetInBeginSection": 328, "offsetInEndSection": 618, "text": " Using antibodies raised against mouse RBM6 to immunostain mammalian cell lines we found that the endogenous protein was both distributed diffusely in the nucleus and concentrated in a small number of nuclear foci that corresponded to splicing speckles/interchromatin granule clusters (IGCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21086038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Subnuclear targeting of the RNA-binding motif protein RBM6 to splicing speckles and nascent transcripts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21086038", "endSection": "title" } ] }, { "body": "What is miravirsen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27924471", "http://www.ncbi.nlm.nih.gov/pubmed/27805315", "http://www.ncbi.nlm.nih.gov/pubmed/26503793", "http://www.ncbi.nlm.nih.gov/pubmed/28389707" ], "ideal_answer": [ "Miravirsen is the first miRNA-targeting drug for the treatment of hepatitis C.", "Miravirsen is an AntimiR-122 for hepatitis C virus infection. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication." ], "type": "summary", "id": "5a7361d83b9d13c708000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Only 20 years after the discovery of small non-coding, single-stranded ribonucleic acids, so-called microRNAs (miRNAs), as post-transcriptional gene regulators, the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924471", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 293, "text": "the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924471", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 307, "text": "Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27805315", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 905, "text": "Miravirsen is an AntimiR-122 for hepatitis C virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389707", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 263, "text": "MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus replication. Administration of miravirsen, an anti-miR-122 oligonucleotide, resulted in a dose dependent and prolonged decrease in HCV RNA levels in chronic hepatitis C patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503793", "endSection": "abstract" } ] }, { "body": "Centor criteria are used for which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27618925", "http://www.ncbi.nlm.nih.gov/pubmed/11719744", "http://www.ncbi.nlm.nih.gov/pubmed/26934845", "http://www.ncbi.nlm.nih.gov/pubmed/23613571", "http://www.ncbi.nlm.nih.gov/pubmed/19054454", "http://www.ncbi.nlm.nih.gov/pubmed/26141740", "http://www.ncbi.nlm.nih.gov/pubmed/27358410", "http://www.ncbi.nlm.nih.gov/pubmed/27573720", "http://www.ncbi.nlm.nih.gov/pubmed/29045629", "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "http://www.ncbi.nlm.nih.gov/pubmed/23783139", "http://www.ncbi.nlm.nih.gov/pubmed/28469911", "http://www.ncbi.nlm.nih.gov/pubmed/15231926", "http://www.ncbi.nlm.nih.gov/pubmed/28991775", "http://www.ncbi.nlm.nih.gov/pubmed/27439523", "http://www.ncbi.nlm.nih.gov/pubmed/22432746" ], "ideal_answer": [ "Centor criteria were developed to diagnose streptococcal pharyngitis." ], "exact_answer": [ "streptococcal pharyngitis" ], "type": "factoid", "id": "5a6f960fb750ff445500005c", "snippets": [ { "offsetInBeginSection": 292, "offsetInEndSection": 486, "text": "Methods: MEDLINE was searched for prospective studies that reported throat culture for both GAS and non-GAS as a reference standard, and reported at least one sign, symptom, or the Centor score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29045629", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 616, "text": "METHODS: Trained pharmacy staff assessed patients presenting with a sore throat using the Centor scoring system and patients meeting three or all four of the criteria were offered a throat swab test for Streptococcus pyogenes, Lancefield group A streptococci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27439523", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1605, "text": "CONCLUSION: Clinician judgement and Centor score are inadequate tools for clinical decision-making for children presenting with sore throat. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26934845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "A Study to Determine if Addition of Palatal Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 445, "text": "Objective. A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children. Hypothesis. In children, Centor Criteria does not cover all the symptoms and signs of acute strep pharyngitis. We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "abstract" }, { "offsetInBeginSection": 1831, "offsetInEndSection": 2021, "text": "Conclusion. Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal pharyngitis in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Appropriateness of diagnosis of streptococcal pharyngitis among Thai community pharmacists according to the Centor criteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573720", "endSection": "title" }, { "offsetInBeginSection": 220, "offsetInEndSection": 428, "text": "Objective To ascertain the appropriateness of diagnosis of streptococcal pharyngitis among Thai community pharmacists according to the Centor criteria and to identify factors related to antibiotic dispensing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573720", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1178, "text": "Main outcome measure The appropriateness of diagnosis of streptococcal pharyngitis according to the original and modified Centor criteria and determinants of antibiotic dispensing including demographic characteristics of pharmacists, knowledge on pharyngitis, and attitudes and control beliefs on antibiotic dispensing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573720", "endSection": "abstract" }, { "offsetInBeginSection": 2289, "offsetInEndSection": 2478, "text": "Conclusion Pharmacists who are knowledgeable on the Centor criteria are more likely to appropriately diagnose streptococcal pharyngitis and less likely to dispense antibiotics in such case.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573720", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1078, "text": "Adult men and women, youth and children \u22656\u00a0years of age who consult for sore throat and is judged to have a pharyngotonsillitis, with 3-4 Centor criteria and a positive rapid test for group A streptococci, will be included in the study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27618925", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 273, "text": "Previous studies have shown that the Centor score combined with Rapid Antigen Detection Test (RADT) for Group A Streptococci can reduce unnecessary antibiotic prescribing in patients with sore throat. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26141740", "endSection": "abstract" }, { "offsetInBeginSection": 1711, "offsetInEndSection": 2095, "text": "Spectrum bias was present, inasmuch as RADT sensitivity increased with Centor scores, ie, 47% sensitivity among children with 0 Centor criteria, 65% among those with 1 criterion, 82% among those with 2 criteria, and 90% among those with 3 or 4 criteria.
CONCLUSIONS: The sensitivity of RADT for GABHS pharyngitis is not a fixed value but varies with the severity of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15231926", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1710, "text": "The prevalence of GABHS pharyngitis was 18% among patients with 0 Centor criteria, 16% among those with 1 criterion, 32% among those with 2 criteria, and 50% among those with 3 or 4 criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15231926", "endSection": "abstract" }, { "offsetInBeginSection": 2096, "offsetInEndSection": 2308, "text": "However, even among pediatric patients with > or =3 Centor criteria for GABHS pharyngitis, the sensitivity of RADT is still too low to support the use of RADT without culture confirmation of negative results.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15231926", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 162, "text": "A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "if Addition of Palatal Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "title" }, { "offsetInBeginSection": 1844, "offsetInEndSection": 2022, "text": "Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal pharyngitis in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 435, "text": "The Centor scoring system can help to identify those patients who have higher likelihood of group A streptococcal infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22432746", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 444, "text": "We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "INTRODUCTION Centor criteria (fever >38.5\u00b0C, swollen, tender anterior cervical lymph nodes, tonsillar exudate and absence of cough) are an algorithm to assess the probability of group A \u03b2 haemolytic Streptococcus (GABHS) as the origin of sore throat, developed for adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "appropriateness of diagnosis of streptococcal pharyngitis among thai community pharmacists according to the centor criteria", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573720", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 951, "text": "Diagnosing GABHS (Group A-beta Hemolytic Streptococcus) tonsillopharyngitis by clinical scoring is a recommended approach in developed countries, but there is still much controversy for low resource settings.We aimed to assess the impact of Centor criteria with the support of practical laboratory tests.We prospectively included patients complaining sore throat (N = 282). We evaluated them in terms of Centor scoring and performed white blood cell count (WBC), C-reactive protein (CRP), rapid antigen detecting test, and throat culture.In GABHS cases (N = 32, 11\u00b73%), two of the criteria were observed to be positive in more than half of the cases (N = 19, 59\u00b73%), while 13 (40\u00b77%) cases met three/four criteria. The specificity of having two criteria was found to be 65\u00b75% and increased to 91\u00b75% after including CRP and WBC.Centor criteria could be safely used to reduce unnecessary antibiotic usage for tonsillopharyngitis in developing countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23783139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2198, "text": "Rapid antigen detection testing (RADT) is often performed for diagnosis of group A beta-hemolytic streptococcal (GABHS) pharyngitis among children. Among adults, the sensitivity of this test varies on the basis of disease severity (spectrum bias). A similar phenomenon may occur when this test is used in a pediatric population, which may affect the need for culture confirmation of all negative RADT results.To assess the performance of a clinical scoring system and to determine whether RADT spectrum bias is present among children who are evaluated for GABHS pharyngitis.Laboratory and clinical records for a consecutive series of pediatric patients who underwent RADT at the Marshfield Clinic between January 2002 and March 2002 were reviewed retrospectively. Patients were stratified according to the number of clinical features present by using modified Centor criteria, ie, history of fever, absence of cough, presence of pharyngeal exudates, and cervical lymphadenopathy. The sensitivity of the RADT was defined as the number of patients with positive RADT results divided by the number of patients with either positive RADT results or negative RADT results but positive throat culture results.RADT results were positive for 117 of 561 children (21%), and culture results were positive for 35 of 444 children (8%) with negative RADT results. The overall prevalence of GABHS pharyngitis was 27% (95% confidence interval: 23-31%). The prevalence of GABHS pharyngitis was 18% among patients with 0 Centor criteria, 16% among those with 1 criterion, 32% among those with 2 criteria, and 50% among those with 3 or 4 criteria. Spectrum bias was present, inasmuch as RADT sensitivity increased with Centor scores, ie, 47% sensitivity among children with 0 Centor criteria, 65% among those with 1 criterion, 82% among those with 2 criteria, and 90% among those with 3 or 4 criteria.The sensitivity of RADT for GABHS pharyngitis is not a fixed value but varies with the severity of disease. However, even among pediatric patients with > or =3 Centor criteria for GABHS pharyngitis, the sensitivity of RADT is still too low to support the use of RADT without culture confirmation of negative results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15231926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1833, "text": "Centor criteria (fever >38.5\u00b0C, swollen, tender anterior cervical lymph nodes, tonsillar exudate and absence of cough) are an algorithm to assess the probability of group A \u03b2 haemolytic Streptococcus (GABHS) as the origin of sore throat, developed for adults. We wanted to evaluate the correlation between Centor criteria and presence of GABHS in children with sore throat admitted to our paediatric emergency department (PED).Retrospective cohort study.The emergency department of a large tertiary university hospital in Brussels, with over 20 000 yearly visits for children below age 16.All medical records (from 2008 to 2010) of children between ages 2 and 16, who were diagnosed with pharyngitis, tonsillitis or sore throat and having a throat swab culture for GABHS. Children with underlying chronic respiratory, cardiac, haematological or immunological diseases and children who had already received antibiotics (AB) prior to the PED consult were excluded. Only records with a full disease history were selected. Out of a total 2118 visits for sore throats, 441 met our criteria. The children were divided into two age groups, 2-5 and 5-16 years.The prevalence of GABHS was higher in the older children compared to the preschoolers (38.7 vs 27.6; p=0.01), and the overall prevalence was 32%. There was no significant difference in the prevalence of GABHS for all different Centor scores within an age group. Likelihood ratios (LR) demonstrate that none of the individual symptoms or a Centor score of \u22653 seems to be effective in ruling in or ruling out GABHS. Pooled LR (CI) for Centor \u22653 was 0.67 (CI 0.50 to 0.90) for the preschoolers and 1.37 (CI 1.04 to 1.79) for the older children.Our results confirm the ineffectiveness of Centor criteria as a predicting factor for finding GABHS in a throat swab culture in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1643, "text": "The European Society for Clinical Microbiology and Infectious Diseases established the Sore Throat Guideline Group to write an updated guideline to diagnose and treat patients with acute sore throat. In diagnosis, Centor clinical scoring system or rapid antigen test can be helpful in targeting antibiotic use. The Centor scoring system can help to identify those patients who have higher likelihood of group A streptococcal infection. In patients with high likelihood of streptococcal infections (e.g. 3-4 Centor criteria) physicians can consider the use of rapid antigen test (RAT). If RAT is performed, throat culture is not necessary after a negative RAT for the diagnosis of group A streptococci. To treat sore throat, either ibuprofen or paracetamol are recommended for relief of acute sore throat symptoms. Zinc gluconate is not recommended to be used in sore throat. There is inconsistent evidence of herbal treatments and acupuncture as treatments for sore throat. Antibiotics should not be used in patients with less severe presentation of sore throat, e.g. 0-2 Centor criteria to relieve symptoms. Modest benefits of antibiotics, which have been observed in patients with 3-4 Centor criteria, have to be weighed against side effects, the effect of antibiotics on microbiota, increased antibacterial resistance, medicalisation and costs. The prevention of suppurative complications is not a specific indication for antibiotic therapy in sore throat. If antibiotics are indicated, penicillin V, twice or three times daily for 10 days is recommended. At the present, there is no evidence enough that indicates shorter treatment length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22432746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1952, "text": "A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children.In children, Centor Criteria does not cover all the symptoms and signs of acute strep pharyngitis. We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children.One hundred patients with a complaint of sore throat were enrolled in the study. All the patients were examined clinically using the Centor Criteria. They were also examined for other signs and symptoms like petechial lesions over the palate, abdominal pain, and skin rash. All the patients were given rapid strep tests, and throat cultures were sent. No antibiotics were given until culture results were obtained.The sample size was 100 patients. All 100 had fever, sore throat, and erythema of tonsils. Twenty of the 100 patients had tonsillar exudates, 85/100 had tender anterior cervical lymph nodes, and 86/100 had no cough. In total, 9 out of the 100 patients had positive throat cultures. We observed that petechiae over the palate, a very significant sign, is not included in the Centor Criteria. Palatal petechiae were present in 8 out of the 100 patients. Six out of these 8 with palatal petechiae had positive throat culture for strep (75%). Only 7 out of 20 with exudates had positive strep culture. Sixteen out of the 100 patients had rapid strep test positive. Those 84/100 who had negative rapid strep also had negative throat culture.We used Fisher's exact test, comparing throat culture positive and negative versus presence of exudates and palatal hemorrhages with positive and negative throat cultures and the resultant P value <.0001.Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal pharyngitis in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1597, "text": "we evaluate the test characteristics and test for spectrum bias of a rapid antigen test for group a beta hemolytic streptococcal gabhs pharyngitis among adults medical record and laboratory results of consecutive adult patients receiving a rapid antigen test for gabhs in the emergency department or urgent care clinic of an urban teaching hospital between august 1999 and december 1999 were analyzed patients were stratified according to the number of clinical features present using the following modified centor criteria history of fever absence of cough presence of pharyngeal exudate and cervical lymphadenopathy the sensitivity of the rapid antigen test was defined as the number of patients with positive rapid antigen test results divided by the number of patients with either positive rapid antigen test results or negative rapid antigen test results and positive throat culture results in the study sample of 498 patient visits the prevalence of gabhs pharyngitis was 28 95 confidence interval ci 24 to 32 the prevalence of gabhs pharyngitis increased as modified centor scores increased 0 or 1 14 2 20 3 43 and 4 52 an increased number of modified centor criteria 0 or 1 2 3 4 was associated with increased rapid antigen test sensitivity 61 76 90 and 97 respectively mantel haenszel trend test p 001 the sensitivity of the rapid antigen test for gabhs is not a fixed value but varies with the spectrum of disease among adults with 3 or 4 clinical criteria for gabhs pharyngitis further study may reveal that culture confirmation of negative rapid antigen test results are not necessary.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11719744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1301, "text": "to determine the validity of the rapid antigen test rat osom strepa genzyme for the diagnosis of acute pharyngitis caused by group a beta haemolytic strep gabhs diagnostic techniques survey urban primary care centre spain all patients over 14 years old seen in 6 surgeries with sore throat and 2 or more centor criteria pharyngotonsillar exudate tender laterocervical nodes absence of coughing and or history or presence of fever pharyngeal swabs were taken from all the patients one for rat and another to send for culture in the microbiology department a total of 182 patients were evaluable with a mean age of 30 6 12 1 years of which 116 were women 63 7 63 patients had 2 centor criteria 83 had 3 and 36 the 4 criteria the culture was positive in 102 patients 56 with gabhs showing infection in forty 22 95 confidence interval ci 21 2 22 8 group c streptococcus was isolated in 26 patients 14 3 gabhs was higher among patients with four centor criteria 38 9 vs 25 3 observed among those with 3 criteria and 7 9 with 2 criteria p 001 sensitivity of rat was 95 with a specificity of 93 a positive predictive value of 79 2 and a negative predictive value of 98 5 these results show the usefulness of rat for diagnosing streptococcal pharyngitis its use should be spread to all primary care practices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19054454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2339, "text": "acute sore throat is a common presentation in primary care settings we aimed to improve our compliance with national antibiotic guidelines for sore throat symptoms to 90 in 3 months time period the national guidelines are based on centor criteria a retrospective audit of 102 patient records with sore throat symptoms presenting between 1 january to 30 december 2015 showed that over 50 were given antibiotics those who were prescribed antibiotics 27 did not meet nice criteria and 85 of patients were given immediate antibiotic prescription centor criteria was documented in just 2 of cases compliance with correct antibiotic course length was 15 antibiotic choice and dose was correct in 94 and 92 of cases respectively antibiotic frequency was correctly prescribed in 100 of patients we introduced interventions that included oral and poster presentations to multidisciplinary team dissemination of guidelines through internal e mail and systemic changes to gp electronic patient record system emis this involved creating an automated sore throat template and information page on re auditing of 71 patients after two pdsa cycles compliance with nice criteria was 87 with a significant reduction in immediate prescribing 66 centor criteria documentation was 42 correct antibiotic course length was prescribed in over 30 of cases other antibiotic regimen parameters choice dose and frequency were correct in 100 of cases the initial results demonstrated that significant changes were needed in particular reducing the amount of antibiotics prescribed by increasing compliance with nice criteria and ensuring all parameters of antibiotic prescription were correct we showed that significant sustainable improvement is achievable through carefully devised automated systemic changes that provides critical information in readily accessible format and does not solely rely on prescribers knowledge and initiative the outcome of these interventions are a decrease in immediate antibiotic prescription significant increase in centor criteria documentation and an increase in compliance with the correct course length of antibiotics all these measures would contribute to reduction in antimicrobial resistance and improvement in patient care in the community future work must focus on improving compliance with correct antibiotic course length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28469911", "endSection": "abstract" } ] }, { "body": "Does Enzastaurin improve survival of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26643807", "http://www.ncbi.nlm.nih.gov/pubmed/22413865", "http://www.ncbi.nlm.nih.gov/pubmed/27052640", "http://www.ncbi.nlm.nih.gov/pubmed/25398844", "http://www.ncbi.nlm.nih.gov/pubmed/23911595", "http://www.ncbi.nlm.nih.gov/pubmed/20124186", "http://www.ncbi.nlm.nih.gov/pubmed/20150385", "http://www.ncbi.nlm.nih.gov/pubmed/28259301" ], "ideal_answer": [ "No. Treatment with enzastaurin does not improve survival of glioblastoma patients." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D016019", "https://meshb.nlm.nih.gov/record/ui?ui=D005909", "http://www.biosemantics.org/jochem#4240085", "http://www.disease-ontology.org/api/metadata/DOID:3068", "https://meshb.nlm.nih.gov/record/ui?ui=D013534" ], "type": "yesno", "id": "5a737e233b9d13c70800000d", "snippets": [ { "offsetInBeginSection": 542, "offsetInEndSection": 1014, "text": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "endSection": "abstract" }, { "offsetInBeginSection": 1744, "offsetInEndSection": 1929, "text": "Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26643807", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 840, "text": "So far, inhibition of angiogenesis by compounds such as bevacizumab, cediranib, enzastaurin or cilengitide as well as alternative dosing schedules of temozolomide did not prolong survival, neither at primary diagnosis nor at recurrent disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27052640", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 927, "text": "Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398844", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1097, "text": "EXPERT OPINION: Enzastaurin and cediranib failed in randomized Phase III trials in recurrent glioblastoma, aflibercept in Phase II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22413865", "endSection": "abstract" }, { "offsetInBeginSection": 1598, "offsetInEndSection": 1774, "text": "Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124186", "endSection": "abstract" }, { "offsetInBeginSection": 1526, "offsetInEndSection": 1867, "text": "Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P < or = .001).
CONCLUSION: Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124186", "endSection": "abstract" }, { "offsetInBeginSection": 1650, "offsetInEndSection": 1826, "text": "Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124186", "endSection": "abstract" }, { "offsetInBeginSection": 1516, "offsetInEndSection": 1684, "text": "Enzastaurin has anti-glioma activity in patients with recurrent high-grade glioma, but does not appear to have enough single-agent activity to be useful as monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20150385", "endSection": "abstract" }, { "offsetInBeginSection": 1766, "offsetInEndSection": 1951, "text": "Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26643807", "endSection": "abstract" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1828, "text": "CONCLUSION Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1695, "text": "glioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results we performed a systematic review and a meta analysis to clarify and evaluate their effectiveness in glioblastoma patients we searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from january 2006 to january 2016 in medline web of science asco esmo and sno databases fourteen randomized clinical trials were identified 7 with bevacizumab 2 cilengitide 1 enzastaurin 1 dasatinib 1 vandetanib 1 temsirolimus 1 cediranib including 4330 patients antiangiogenic drugs showed no improvement in overall survival with a pooled hr of 1 00 a trend for an inferior outcome in terms of overall survival was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone hr 1 24 p 0 056 bevacizumab did not improve overall survival twelve trials 4113 patients were analyzed for progression free survival among antiangiogenic drugs only bevacizumab demonstrated an improvement of progression free survival hr 0 63 p 0 001 both alone hr 0 60 p 0 003 or in combination to chemotherapy hr 0 63 p 0 001 both as first line treatment hr 0 70 p 0 001 or in recurrent disease hr 0 52 p 0 001 antiangiogenic drugs did not improve overall survival in glioblastoma patients either as first or second line treatment and either as single agent or in combination with chemotherapy among antiangiogenic drugs only bevacizumab improved progression free survival regardless of treatment line both as single agent or in combination with chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1185, "text": "glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation highlighting the potential value of treatments targeting angiogenesis antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action ultimately however alternative proangiogenic signal transduction pathways are activated leading to the development of resistance even in tumors that initially respond the identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority despite promising phase ii clinical trial results and patient benefit in terms of clinical improvement and longer progression free survival an overall survival benefit has not been demonstrated in four randomized phase iii trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma however future studies are warranted predictive markers may allow appropriate patient enrichment combination with chemotherapy may ultimately prove successful in improving overall survival and novel agents targeting multiple proangiogenic pathways may prove effective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1684, "text": "this phase iii open label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma who grade 4 patients were randomly assigned 2 1 to receive 6 week cycles of enzastaurin 500 mg d 1 125 mg loading dose day 1 or lomustine 100 to 130 mg m 2 day 1 assuming a 45 improvement in progression free survival pfs 397 patients were required to provide 80 power to achieve statistical significance at a one sided level of 025 enrollment was terminated at 266 patients enzastaurin n 174 lomustine n 92 after a planned interim analysis for futility patient characteristics were balanced between arms median pfs 1 5 v 1 6 months hazard ratio hr 1 28 95 ci 0 97 to 1 70 overall survival 6 6 v 7 1 months hr 1 20 95 ci 0 88 to 1 65 and 6 month pfs rate p 13 did not differ significantly between enzastaurin and lomustine respectively stable disease occurred in 38 5 and 35 9 of patients and objective response occurred in 2 9 and 4 3 of patients respectively time to deterioration of physical and functional well being and symptoms did not differ between arms hr 1 12 p 54 four patients discontinued enzastaurin because of drug related serious adverse events aes eleven patients treated with enzastaurin died on study four because of aes one was drug related all four deaths that occurred in patients receiving lomustine were disease related grade 3 to 4 hematologic toxicities were significantly higher with lomustine 46 events than with enzastaurin one event p or 001 enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20124186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1700, "text": "this study s primary objective was evaluation of the progression free survival rate at 6 months pfs 6 in patients with newly diagnosed glioblastoma without o 6 methylguanine dna methyltransferase mgmt promoter hypermethylation postsurgically treated with enzastaurin before and concomitantly with radiation therapy followed by enzastaurin maintenance therapy pfs 6 of at least 55 was set to be relevant compared with the data of the eortc 26981 22981 ncic ce 3 trial adult patients with a life expectancy of at least 12 weeks who were newly diagnosed with a histologically proven supratentorial glioblastoma without mgmt promoter hypermethylation were eligible patients were treated with enzastaurin prior to concomitantly with and after standard partial brain radiotherapy here we report on a multicenter open label uncontrolled phase ii study of patients with newly diagnosed glioblastoma without mgmt promoter hypermethylation treated with enzastaurin and radiation therapy within 4 study periods pfs 6 was 53 6 95 confidence interval ci 39 8 65 6 the median overall survival was 15 0 months 95 ci 11 9 17 9 for all patients 3 9 months 95 ci 0 8 9 0 for patients with biopsy 15 4 months 95 ci 10 1 17 9 for patients with partial resection and 18 9 months 95 ci 13 9 28 5 for patients with complete resection the safety profile in this study was as expected from previous trials and the therapy was well tolerated pfs 6 missed the primary planned outcome of 55 the secondary exploratory analysis according to resection status of the different subgroups of patients with biopsies partial resection and complete resection demonstrates the strong prognostic influence of resection on overall survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23911595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1838, "text": "we evaluated the efficacy of combination enzastaurin ly317615 and bevacizumab for recurrent malignant gliomas and explored serologic correlates we enrolled 81 patients with glioblastomas gbm n 40 and anaplastic gliomas ag n 41 patients received enzastaurin as a loading dose of 1125 mg followed by 500 or 875 mg daily for patients on non enzyme inducing or enzyme inducing antiepileptics respectively patients received bevacizumab 10 mg kg intravenously biweekly clinical evaluations were repeated every 4 weeks magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset phosphorylated glycogen synthase kinase gsk 3 levels from peripheral blood mononuclear cells pbmcs were checked with each mri median overall survival was 7 5 and 12 4 months for glioblastomas and anaplastic glioma cohorts with median progression free survivals of 2 0 and 4 4 months respectively of gbm patients 3 40 7 5 were not evaluable while 8 37 22 had partial or complete response and 20 37 54 had stable disease for 2 months of the 39 evaluable ag patients 18 46 had an objective response and 16 41 had stable disease for 2 months the most common grade 3 toxicities were lymphopenia 15 hypophosphatemia 8 8 and thrombotic events 7 5 two 2 5 gbm patients died suddenly another death 1 3 occurred from intractable seizures phosphorylated gsk 3 levels from pbmcs did not correlate with treatment response a minimally important improvement in health related quality of life was self reported in 7 9 24 29 2 37 5 early response based on levin criteria was significantly associated with significantly longer progression free survival for glioblastomas enzastaurin ly317615 in combination with bevacizumab for recurrent malignant gliomas is well tolerated with response and progression free survival similar to bevacizumab monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26643807", "endSection": "abstract" } ] }, { "body": "Is Tofacitinib effective for Ulcerative Colitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22894574", "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "http://www.ncbi.nlm.nih.gov/pubmed/27663846", "http://www.ncbi.nlm.nih.gov/pubmed/28503977", "http://www.ncbi.nlm.nih.gov/pubmed/28164724", "http://www.ncbi.nlm.nih.gov/pubmed/28158411", "http://www.ncbi.nlm.nih.gov/pubmed/27140405", "http://www.ncbi.nlm.nih.gov/pubmed/27699641", "http://www.ncbi.nlm.nih.gov/pubmed/28601639", "http://www.ncbi.nlm.nih.gov/pubmed/28790099", "http://www.ncbi.nlm.nih.gov/pubmed/25651782", "http://www.ncbi.nlm.nih.gov/pubmed/28475384", "http://www.ncbi.nlm.nih.gov/pubmed/26608188" ], "ideal_answer": [ "Yes. Tofacitinib, an oral small-molecule Janus kinase inhibitor, is effective in the treatment of moderate-severe ulcerative colitis. It is also effective treatment of rheumatoid arthritis and autoimmune encephalomyelitis." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8577", "https://meshb.nlm.nih.gov/record/ui?ui=D016896", "https://meshb.nlm.nih.gov/record/ui?ui=D003093" ], "type": "yesno", "id": "5a723edd2dc08e987e00000c", "snippets": [ { "offsetInBeginSection": 879, "offsetInEndSection": 1027, "text": "Tofacitinib, inhibiting signalling via all Janus kinase family members, was effective in phase 2 and 3 trials in moderate-severe ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28158411", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 564, "text": "Among them, Janus kinase (JAK) inhibitors seem to have the lead, since tofacitinib has received regulatory approval in 2012 for the treatment of rheumatoid arthritis, and also it has shown a favorable risk-benefit ratio in phase 3 studies for ulcerative colitis, both in anti-TNF na\u00efve and anti-TNF experienced patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28164724", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1116, "text": "Near future conventional drug options include oral agents such as tofacitinib and mongersen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28475384", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 781, "text": "Tofacitinib showed dose related efficacy for induction therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 2243, "offsetInEndSection": 2404, "text": "CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 295, "text": "Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28601639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 1932, "offsetInEndSection": 2444, "text": "Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.
CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 294, "text": "Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28601639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28790099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "BACKGROUND Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND Tofacitinib, a novel, oral Janus kinase inhibitor, demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis (UC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25651782", "endSection": "abstract" }, { "offsetInBeginSection": 2249, "offsetInEndSection": 2409, "text": "CONCLUSIONS In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 409, "text": "Tofacitinib, an oral janus kinase inhibitor, is a new biologic that has shown promise in the treatment of ulcerative colitis and may be effective in the treatment of Crohn's disease according to phase 2 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27663846", "endSection": "abstract" }, { "offsetInBeginSection": 2066, "offsetInEndSection": 2252, "text": "CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574", "endSection": "abstract" }, { "offsetInBeginSection": 1996, "offsetInEndSection": 2285, "text": "Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500.
CONCLUSIONS: Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2467, "text": "tofacitinib an oral small molecule janus kinase inhibitor was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial we further evaluated the efficacy of tofacitinib as induction and maintenance therapy we conducted three phase 3 randomized double blind placebo controlled trials of tofacitinib therapy in adults with ulcerative colitis in the octave induction 1 and 2 trials 598 and 541 patients respectively who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib 10 mg twice daily or placebo for 8 weeks the primary end point was remission at 8 weeks in the octave sustain trial 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib either 5 mg or 10 mg twice daily or placebo for 52 weeks the primary end point was remission at 52 weeks in the octave induction 1 trial remission at 8 weeks occurred in 18 5 of the patients in the tofacitinib group versus 8 2 in the placebo group p 0 007 in the octave induction 2 trial remission occurred in 16 6 versus 3 6 p 0 001 in the octave sustain trial remission at 52 weeks occurred in 34 3 of the patients in the 5 mg tofacitinib group and 40 6 in the 10 mg tofacitinib group versus 11 1 in the placebo group p 0 001 for both comparisons with placebo in the octave induction 1 and 2 trials the rates of overall infection and serious infection were higher with tofacitinib than with placebo in the octave sustain trial the rate of serious infection was similar across the three treatment groups and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo across all three trials adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo as compared with placebo tofacitinib was associated with increased lipid levels in patients with moderately to severely active ulcerative colitis tofacitinib was more effective as induction and maintenance therapy than placebo funded by pfizer octave induction 1 octave induction 2 and octave sustain clinicaltrials gov numbers nct01465763 nct01458951 and nct01458574 respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2176, "text": "ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective one additional treatment may be tofacitinib cp 690 550 an oral inhibitor of janus kinases 1 2 and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2 which is expected to block signaling involving gamma chain containing cytokines including interleukins 2 4 7 9 15 and 21 these cytokines are integral to lymphocyte activation function and proliferation in a double blind placebo controlled phase 2 trial we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis patients were randomly assigned to receive tofacitinib at a dose of 0 5 mg 3 mg 10 mg or 15 mg or placebo twice daily for 8 weeks the primary outcome was a clinical response at 8 weeks defined as an absolute decrease from baseline in the score on the mayo scoring system for assessment of ulcerative colitis activity possible score 0 to 12 with higher scores indicating more severe disease of 3 or more and a relative decrease from baseline of 30 or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1 the primary outcome clinical response at 8 weeks occurred in 32 48 61 and 78 of patients receiving tofacitinib at a dose of 0 5 mg p 0 39 3 mg p 0 55 10 mg p 0 10 and 15 mg p 0 001 respectively as compared with 42 of patients receiving placebo clinical remission defined as a mayo score 2 with no subscore 1 at 8 weeks occurred in 13 33 48 and 41 of patients receiving tofacitinib at a dose of 0 5 mg p 0 76 3 mg p 0 01 10 mg p 0 001 and 15 mg p 0 001 respectively as compared with 10 of patients receiving placebo there was a dose dependent increase in both low density and high density lipoprotein cholesterol three patients treated with tofacitinib had an absolute neutrophil count of less than 1500 patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo funded by pfizer clinicaltrials gov number nct00787202.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 851, "text": "recently several medical treatments for ulcerative colitis uc have been developed including 5 aminosalicylic acids 5 asas corticosteroids thiopurine calcineurin inhibitors and anti tumor necrosis factor tnf \u03b1 treatments treatment options including calcineurin inhibitors and anti tnf treatment for refractory uc are discussed in this article furthermore upcoming treatments are introduced such as golimumab vedolizumab ajm300 tofacitinib budesonide foamwill be used as one treatment option in patients with distal colitis herbal medicine such as qing dai is also effective for active uc and may be useful for patients who are refractory to anti tnf\u03b1 treatments in the near future physicians will able to use many different treatments for uc patients however we should not forget 5 asa and corticosteroids as the fundamental treatments for uc patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27699641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1420, "text": "the inflammatory diseases ulcerative colitis and crohn s disease constitute the two main forms of inflammatory bowel disease ibd they are characterized by chronic relapsing inflammation of the gastrointestinal tract significantly impacting on patient quality of life and often requiring prolonged treatment existing therapies for ibd are not effective for all patients and an unmet need exists for additional therapies to induce and maintain remission here we describe the mechanism of action of the janus kinase jak inhibitor tofacitinib for the treatment of ibd and the effect of jak inhibition on the chronic cycle of inflammation that is characteristic of the disease the pathogenesis of ibd involves a dysfunctional response from the innate and adaptive immune system resulting in overexpression of multiple inflammatory cytokines many of which signal through jaks thus jak inhibition allows multiple cytokine signaling pathways to be targeted and is expected to modulate the innate and adaptive immune response in ibd thereby interrupting the cycle of inflammation tofacitinib is an oral small molecule jak inhibitor that is being investigated as a targeted immunomodulator for ibd clinical development of tofacitinib and other jak inhibitors is ongoing with the aspiration of providing new treatment options for ibd that have the potential to deliver prolonged efficacy and clinically meaningful patient benefits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26608188", "endSection": "abstract" } ] }, { "body": "Which are the main transcriptional activators of circadian oscillations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24320178", "http://www.ncbi.nlm.nih.gov/pubmed/20967239", "http://www.ncbi.nlm.nih.gov/pubmed/12897057", "http://www.ncbi.nlm.nih.gov/pubmed/18177499", "http://www.ncbi.nlm.nih.gov/pubmed/11798163", "http://www.ncbi.nlm.nih.gov/pubmed/19917250", "http://www.ncbi.nlm.nih.gov/pubmed/19571382" ], "ideal_answer": [ "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop.", "BMAL1 and CLOCK.", "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. We have examined abundance, posttranslational modifications, cellular localization of endogenous and ectopically expressed CLOCK and BMAL1 proteins. Nuclear/cytoplasm distribution of CLOCK was found to be under circadian regulation.", "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. Nuclear/cytoplasm distribution of CLOCK was found to be under circadian regulation. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG).", "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. We have examined abundance, posttranslational modifications, cellular localization of endogenous and ectopically expressed CLOCK and BMAL1 proteins. Formation of CLOCK/BMAL1 complex following ectopic coexpression of both proteins is followed by their codependent phosphorylation, which is tightly coupled to CLOCK nuclear translocation and degradation" ], "exact_answer": [ [ "BMAL1" ], [ "CLOCK" ] ], "type": "list", "id": "5a86ebf2faa1ab7d2e000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12897057", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 531, "text": " We have examined abundance, posttranslational modifications, cellular localization of endogenous and ectopically expressed CLOCK and BMAL1 proteins. Nuclear/cytoplasm distribution of CLOCK was found to be under circadian regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12897057", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 945, "text": "Formation of CLOCK/BMAL1 complex following ectopic coexpression of both proteins is followed by their codependent phosphorylation, which is tightly coupled to CLOCK nuclear translocation and degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12897057", "endSection": "abstract" }, { "offsetInBeginSection": 1318, "offsetInEndSection": 1514, "text": "Altogether, these results provide evidence for an additional level of circadian system control, which is based on regulation of transcriptional activity or/and availability of CLOCK/BMAL1 complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12897057", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 336, "text": " Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18177499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Circadian rhythms in mammals are generated by a transcriptional negative feedback loop that is driven primarily by oscillations of PER and CRY, which inhibit their own transcriptional activators, CLOCK and BMAL1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19917250", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1011, "text": "Our biochemical evidence supports an elegant mechanism for the disparity: PER2 directly and rhythmically binds to CLOCK:BMAL1, while CRY only interacts indirectly; PER2 bridges CRY and CLOCK:BMAL1 to drive the circadian negative feedback loop.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19917250", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 336, "text": "Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18177499", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 205, "text": "The CRY proteins in turn inhibit CLOCK:BMAL-mediated transcription closing the negative feedback loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "In the vertebrate circadian feedback loop, CLOCK:BMAL heterodimers induce the expression of Cry genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571382", "endSection": "title" }, { "offsetInBeginSection": 109, "offsetInEndSection": 335, "text": "Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18177499", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 618, "text": "In the present study, we demonstrate that Id2 is involved in stabilization of the amplitudes of the circadian oscillations by suppressing transcriptional activation of clock genes Clock and Bmal1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24320178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1203, "text": "bmal1 is an essential transcriptional activator within the mammalian circadian clock we report here that the suprachiasmatic nucleus scn of bmal1 null mutant mice unexpectedly generates stochastic oscillations with periods that overlap the circadian range dissociated scn neurons expressed fluctuating levels of per2 detected by bioluminescence imaging but could not generate circadian oscillations intrinsically inhibition of intercellular communication or cyclic amp signaling in scn slices which provide a positive feed forward signal to drive the intracellular negative feedback loop abolished the stochastic oscillations propagation of this feed forward signal between scn neurons then promotes quasi circadian oscillations that arise as an emergent property of the scn network experimental analysis and mathematical modeling argue that both intercellular coupling and molecular noise are required for the stochastic rhythms providing a novel biological example of noise induced oscillations the emergence of stochastic circadian oscillations from the scn network in the absence of cell autonomous circadian oscillatory function highlights a previously unrecognized level of circadian organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20967239", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1164, "text": "transcriptional regulation appears to be fundamental to circadian oscillations of clock gene expression these oscillations are believed to control output rhythms the transcriptional feedback loop and a model of interlocked loops have been proposed as the basis for these oscillations we characterized the genomic structure of the mouse bmal1 gene mbmal1 and defined the mbmal1 promoter region transcription of mbmal1 was activated by cry1 cry2 and per2 and was repressed by bmal1 clock dimers therefore cry per2 and bmal1 clock play bidirectional roles in transcription when they are at high levels by late day and midnight respectively this underlies the opposite phase of bmal1 compared to cry and per we propose that a bmal1 negative feedback loop interlocks with the cry and per2 negative feedback loop by inter activation forming a third positive forward loop this transcriptional model suggests a molecular basis for the maintenance of stability persistence and period of circadian rhythms the transcriptional potency of cry is predominant within the mammalian clock suggesting a clearance mechanism for cry in period maintenance c 2002 elsevier science usa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11798163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1447, "text": "the circadian expression of the mammalian clock genes is based on transcriptional feedback loops two basic helix loop helix bhlh pas for period arnt sim domain containing transcriptional activators clock and bmal1 are known to regulate gene expression by interacting with a promoter element termed the e box cacgtg the non canonical e boxes or e box like sequences have also been reported to be necessary for circadian oscillation we report a new cis element required for cell autonomous circadian transcription of clock genes this new element consists of a canonical e box or a non canonical e box and an e box like sequence in tandem with the latter with a short interval 6 base pairs between them we demonstrate that both e box or e box like sequences are needed to generate cell autonomous oscillation we also verify that the spacing nucleotides with constant length between these 2 e elements are crucial for robust oscillation furthermore by in silico analysis we conclude that several clock and clock controlled genes possess a direct repeat of the e box like elements in their promoter region we propose a novel possible mechanism regulated by double e box like elements not to a single e box for circadian transcriptional oscillation the direct repeat of the e box like elements identified in this study is the minimal required element for the generation of cell autonomous transcriptional oscillation of clock and clock controlled genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18177499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "clock bmal independent circadian oscillation of zebrafish cryptochrome1a gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571382", "endSection": "title" } ] }, { "body": "Is CREB a key memory protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25031400", "http://www.ncbi.nlm.nih.gov/pubmed/28017136", "http://www.ncbi.nlm.nih.gov/pubmed/28424976", "http://www.ncbi.nlm.nih.gov/pubmed/28752224", "http://www.ncbi.nlm.nih.gov/pubmed/28069295", "http://www.ncbi.nlm.nih.gov/pubmed/28292834" ], "ideal_answer": [ "The creb protein is associated with memory", "Yes, human cyclic AMP response element binding protein (CREB) transcription factor plays a crucial role in memory." ], "exact_answer": "yes", "type": "yesno", "id": "5a893da7bc7bade53a000001", "snippets": [ { "offsetInBeginSection": 145, "offsetInEndSection": 259, "text": "Human cyclic AMP response element binding protein (CREB) transcription factor which plays a crucial role in memory", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28069295", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 319, "text": "The activated CREB is implicated in the regulation of development, protection, learning, memory and plasticity in the nerve system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28017136", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 641, "text": "A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28292834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Transcription factor cAMP response element-binding protein (CREB) plays a critical role in memory formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424976", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 434, "text": "It is well known that molecules like cAMP response element binding (CREB) and binding protein (CBP) play a crucial role in memory consolidation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28752224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "CREB SUMOylation by the E3 ligase PIAS1 enhances spatial memory.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031400", "endSection": "title" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1762, "text": "Therefore, CREB phosphorylation may be responsible for signal transduction during the early phase of long-term memory formation, whereas CREB SUMOylation sustains long-term memory", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031400", "endSection": "abstract" } ] }, { "body": "Which clinical trials for psoriasis involved tofacitinib? (November 2017)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27600367", "http://www.ncbi.nlm.nih.gov/pubmed/27271195", "http://www.ncbi.nlm.nih.gov/pubmed/28396102" ], "ideal_answer": [ "Four phase 3 clinical trials have been performed to assess tofacitinib in psoriasis patients: OPT Retreatment, OPT Pivotal 1, OPT Pivotal 2, OPT Compare" ], "exact_answer": [ [ "OPT Retreatment" ], [ "OPT Pivotal 1" ], [ "OPT Pivotal 2" ], [ "OPT Compare" ] ], "type": "list", "id": "5a7600b983b0d9ea6600000c", "snippets": [ { "offsetInBeginSection": 92, "offsetInEndSection": 251, "text": "A Phase 3 withdrawal/re-treatment study (NCT01186744; OPT Retreatment) showed tofacitinib re-treatment was effective in patients with chronic plaque psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600367", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 458, "text": "In 2 identical phase 3 studies (OPT Pivotal 1 and 2), patients were randomized 2:2:1 to receive tofacitinib 5\u00a0mg, tofacitinib 10\u00a0mg, or placebo, twice daily. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28396102", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 468, "text": "To evaluate HRQoL with tofacitinib, vs. placebo or etanercept, in the Phase 3, randomized, placebo-controlled, non-inferiority, Oral-treatment Psoriasis Trial (OPT) Compare Study (NCT01241591).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271195", "endSection": "abstract" } ] }, { "body": "Which two interleukins are inhibited by Ustekinumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28122069", "http://www.ncbi.nlm.nih.gov/pubmed/22123062", "http://www.ncbi.nlm.nih.gov/pubmed/18703004", "http://www.ncbi.nlm.nih.gov/pubmed/26372543", "http://www.ncbi.nlm.nih.gov/pubmed/20430307", "http://www.ncbi.nlm.nih.gov/pubmed/20071701", "http://www.ncbi.nlm.nih.gov/pubmed/28140549", "http://www.ncbi.nlm.nih.gov/pubmed/19934030", "http://www.ncbi.nlm.nih.gov/pubmed/23349185", "http://www.ncbi.nlm.nih.gov/pubmed/27826996", "http://www.ncbi.nlm.nih.gov/pubmed/23745965", "http://www.ncbi.nlm.nih.gov/pubmed/28280401", "http://www.ncbi.nlm.nih.gov/pubmed/27450626", "http://www.ncbi.nlm.nih.gov/pubmed/22758911", "http://www.ncbi.nlm.nih.gov/pubmed/21436972", "http://www.ncbi.nlm.nih.gov/pubmed/28224166", "http://www.ncbi.nlm.nih.gov/pubmed/20540088", "http://www.ncbi.nlm.nih.gov/pubmed/28423301", "http://www.ncbi.nlm.nih.gov/pubmed/18706417", "http://www.ncbi.nlm.nih.gov/pubmed/28150333", "http://www.ncbi.nlm.nih.gov/pubmed/24410536", "http://www.ncbi.nlm.nih.gov/pubmed/23278559", "http://www.ncbi.nlm.nih.gov/pubmed/19886505", "http://www.ncbi.nlm.nih.gov/pubmed/29042094", "http://www.ncbi.nlm.nih.gov/pubmed/28099816", "http://www.ncbi.nlm.nih.gov/pubmed/28300862", "http://www.ncbi.nlm.nih.gov/pubmed/19882785", "http://www.ncbi.nlm.nih.gov/pubmed/24734995", "http://www.ncbi.nlm.nih.gov/pubmed/20645530", "http://www.ncbi.nlm.nih.gov/pubmed/28087506", "http://www.ncbi.nlm.nih.gov/pubmed/24553909", "http://www.ncbi.nlm.nih.gov/pubmed/20421912", "http://www.ncbi.nlm.nih.gov/pubmed/18486739", "http://www.ncbi.nlm.nih.gov/pubmed/19344192" ], "ideal_answer": [ "Ustekinumab, a monoclonal antibody that binds to the shared p40 subunit of interleukin-12 and interleukin-23, is approved in the USA and Europe for moderate to severe plaque psoriasis." ], "exact_answer": [ [ "interleukin-12" ], [ "interleukin-23" ] ], "type": "list", "id": "5a7244aa2dc08e987e00000f", "snippets": [ { "offsetInBeginSection": 112, "offsetInEndSection": 330, "text": "The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28087506", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 522, "text": "The purpose of this review is to update the reader on treatment options for PsA using conventional synthetic disease modifying agents (csDMARDs) and novel therapies including tumour necrosis factor alpha inhibitors, interleukin 12/23 inhibitor (ustekinumab), the interleukin 17 antagonists including secukinumab, brodalumab, ixekizumab, and the phosphodiesterase-4 inhibitor, apremilast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27826996", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 797, "text": "Expert opinion: Based on the rationale of the involvement of the IL-23/Th17 axis in AS, novel biological agents have been developed and include secukinumab, an anti-IL-17A agent and ustekinumab, an anti-IL-23 antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28099816", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 706, "text": "Besides systemic corticosteroids and cyclosporine A (CsA), options also include intravenous immunoglobulins (IVIG) and biologics such as the TNF\u03b1 inhibitors infliximab, adalimumab, and etanercept; the interleukin (IL) 12/23 antibody ustekinumab; the IL-1 receptor antagonist anakinra; and the IL-1\u03b2 antibody canakinumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28140549", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 569, "text": "Objective: To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28122069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The use of monoclonal antibodies against interleukin (IL)-12 and -23, such as ustekinumab, has considerably reduced the disease burden in many patients with moderate to severe psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28300862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Ustekinumab, a monoclonal antibody that binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, is approved in the USA and Europe for moderate to severe plaque psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28150333", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 680, "text": "The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28280401", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 475, "text": "This study is a retrospective analysis of routine parameter dynamics and laboratory adverse events (LAE) in psoriasis patients on long-term treatment (n\u2009=\u2009199) with tumour necrosis factor (TNF)-\u03b1-antagonists (adalimumab, etanercept), and the interleukin (IL)12/23-antagonist ustekinumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28224166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Ustekinumab is a monoclonal antibody directed against the p40 subunit, which is part of interleukins IL-12 and IL-23.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29042094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The biologic, Ustekinumab (Stelara\u00ae, Centocor, Inc., Malvern, PA, USA), is a fully human monoclonal antibody with a high affinity for the shared p40 subunit of interleukins 12 and 23 (IL-12 and IL-23).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23745965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Ustekinumab is a human monoclonal antibody directed against the shared p40 subunit of interleukins 12 and 23.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27450626", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 738, "text": "A recent example is ustekinumab, a first-in-class therapeutic human immunoglobulin G1 kappa mAb that binds to the interleukins (IL)-12 and IL-23, cytokines that modulate lymphocyte function, including T-helper (Th) 1 and Th17 cell subsets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22123062", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1295, "text": "Ustekinumab (CNTO 1275, Centocor Inc, Malvern, PA, USA) is a human monoclonal antibody that binds to the shared p40 protein subunit of human interleukins 12 and 23 with high affinity and specificity, thereby preventing interaction with their surface IL-12R\u03b21 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21436972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Discovery and mechanism of ustekinumab: a human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22123062", "endSection": "title" }, { "offsetInBeginSection": 266, "offsetInEndSection": 390, "text": "); (2) Ustekinumab is an inhibitor of interleukins 12 and 23, which are believed to be implicated in the onset of psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19882785", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 317, "text": "Ustekinumab (Stelara) is a therapeutic monoclonal antibody (mAb) targeted against the p40 shared subunit of IL-12 and IL-23.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349185", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 701, "text": "In the past years, the IL-23/Th17 axis has emerged as an important mechanism in the pathogenesis of PsA. Ustekinumab, a fully human IgG1\u03ba monoclonal antibody that targets the common subunit p40 of IL-12 and IL-23, has been shown in clinical trials, to be well-tolerated and effective in patients with active PsA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26372543", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 365, "text": "We compared two biologic agents, ustekinumab (an interleukin-12 and interleukin-23 blocker) and etanercept (an inhibitor of tumor necrosis factor alpha), for the treatment of psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20071701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Ustekinumab, a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody that binds with high affinity to human interleukin-12 and interleukin-23, has demonstrated efficacy in patients with psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19934030", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Anti-p40 antibodies ustekinumab and briakinumab: blockade of interleukin-12 and interleukin-23 in the treatment of psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20430307", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18706417", "endSection": "title" }, { "offsetInBeginSection": 127, "offsetInEndSection": 209, "text": "Ustekinumab is a monoclonal antibody against the p40 subunit of interleukin-12/23.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18706417", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 513, "text": "ABT-874 (Abbott Laboratories, Saint-Laurent, QC,) and ustekinumab (CNTO 1275, Ortho Biotech, Toronto, ON) are two monoclonal antibodies against interleukins 12 and 23 (IL-12/23), key mediators of T-cell differentiation in the pathogenesis of psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19886505", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 350, "text": "Ustekinumab is a fully human immunoglobulin G1\u03ba monoclonal antibody that targets the common p40 subunit that is shared by both interleukin (IL)-12 and IL-23, consequently inhibiting T-cell differentiation along both Th1 and Th17 pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23278559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Ustekinumab is a fully human monoclonal antibody directed against the p40 subunit shared by interleukin 12 and interleukin 23, two naturally occurring protein regulators that play an important role in immune-mediated inflammatory diseases, including psoriatic arthritis (PsA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24410536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "BACKGROUND Ustekinumab, a fully human immunoglobulin (Ig) G1K monoclonal antibody directed against the p40 subunit of interleukin (IL)-12/23, has demonstrated efficacy in patients with moderate-to-severe psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20645530", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1296, "text": "Ustekinumab (CNTO 1275, Centocor Inc, Malvern, PA, USA) is a human monoclonal antibody that binds to the shared p40 protein subunit of human interleukins 12 and 23 with high affinity and specificity, thereby preventing interaction with their surface IL-12R\u03b21 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21436972", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 1093, "text": "Ustekinumab is a monoclonal antibody belonging to a newly developed class of biological, anti-cytokine medications that notably targets the p40 subunit of both IL-12 and -23, both naturally occurring proteins that are important in regulating the immune system and are understood to play a role in immune-mediated inflammatory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20421912", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1027, "text": "Ustekinumab binds to the p40 subunit common to IL-12 and IL-23 and prevents their interaction with the IL-12 receptor \u03b21 subunit of the IL-12 and IL-23 receptor complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22123062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "INTRODUCTION Ustekinumab is a human monoclonal antibody directed against the shared p40 subunit of interleukins 12 and 23.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27450626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "BACKGROUND Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of interleukin (IL) 12 and IL-23 and inhibits their pharmacological activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20540088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Ustekinumab is a fully human monoclonal antibody that binds with high specificity and affinity to the cytokines interleukin (IL)-12 and IL-23, thereby suppressing IL-12- and IL-23-mediated inflammation associated with psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19344192", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 360, "text": "Two human anti-p40 monoclonal antibodies targeting both IL-12 and IL-23 via their shared p40 subunit have been developed: briakinumab and ustekinumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22758911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1871, "text": "evaluate ustekinumab an anti interleukin il 12 and il 23 antibody effects on radiographic progression in psoriatic arthritis psa we conducted preplanned integrated analyses of combined radiographic data from psummit 1 and psummit 2 phase 3 randomised controlled trials patients had active psa despite prior conventional and or biologic disease modifying antirheumatic drugs 5 66 swollen 5 68 tender joints c reactive protein 3 0 mg l documented plaque psoriasis patients psummit 1 n 615 psummit 2 n 312 were randomised to ustekinumab 45 mg 90 mg or placebo at weeks wk 0 4 and every q 12 wks at wk 16 patients with 5 improvement in tender swollen joint counts entered blinded early escape all other placebo patients received ustekinumab 45 mg at wk 24 and wk 28 then q 12 wks radiographs of hands feet at wks 0 24 52 were assessed using psa modified van der heijde sharp vdh s scores combined psummit 1 and psummit 2 changes in total vdh s scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis treatment effects were assessed using analysis of variance on van der waerden normal scores factors treatment baseline methotrexate usage and study integrated data analysis results indicated that ustekinumab treated patients regardless of dose demonstrated significantly less radiographic progression at wk 24 than did placebo recipients wk 0 24 total vdh s score mean changes 0 4 combined individual ustekinumab dose groups 1 0 placebo all p 0 02 from wk 24 to wk 52 inhibition of radiographic progression was maintained for ustekinumab treated patients and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 wk 24 wk 52 total vdh s score mean change 0 08 ustekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active psa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "discovery and mechanism of ustekinumab a human monoclonal antibody targeting interleukin 12 and interleukin 23 for treatment of immune mediated disorders", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22123062", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "a randomized trial of ustekinumab a human interleukin 12 23 monoclonal antibody in patients with moderate to severe crohn s disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18706417", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "human leucocyte antigen cw6 as a predictor for clinical response to ustekinumab an interleukin 12 23 blocker in chinese patients with psoriasis a retrospective analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24734995", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1436, "text": "ustekinumab a human immunoglobulin g1 kappa igg1k monoclonal antibody that binds with high affinity to human interleukin 12 and interleukin 23 has demonstrated efficacy in patients with psoriasis the objective of this study was to perform exposure response modeling to increase the understanding of reduction in disease severity following treatment with ustekinumab in patients with moderate to severe psoriasis who participate in two phase iii studies phoenix 1 and phoenix 2 patients were randomly assigned to receive ustekinumab 45 mg or 90 mg n 1312 11 624 psoriasis area and severity index pasi scores or placebo n 665 3278 pasi scores disease severity was assessed using pasi scores a population mechanism based exposure response model of ustekinumab using nonmem was developed using serum ustekinumab concentrations and pasi scores the pharmacodynamic response effect was the reduction in pasi score the placebo effect although minor was also integrated into the model none of the covariate factors evaluated eg demographics baseline disease characteristics comorbidities significantly contributed to the between subject variability in the pharmacodynamic parameters the developed exposure response model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate to severe plaque psoriasis a robust exposure response relationship has been confirmed for ustekinumab in psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19934030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1867, "text": "interleukin 23 is thought to be critical to the pathogenesis of psoriasis we compared risankizumab bi 655066 a humanized igg1 monoclonal antibody that inhibits interleukin 23 by specifically targeting the p19 subunit and thus prevents interleukin 23 signaling and ustekinumab an interleukin 12 and interleukin 23 inhibitor in patients with moderate to severe plaque psoriasis we randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab a single 18 mg dose at week 0 or 90 mg or 180 mg doses at weeks 0 4 and 16 or ustekinumab 45 or 90 mg according to body weight at weeks 0 4 and 16 the primary end point was a 90 or greater reduction from baseline in the psoriasis area and severity index pasi score at week 12 at week 12 the percentage of patients with a 90 or greater reduction in the pasi score was 77 64 of 83 patients for risankizumab 90 mg and 180 mg groups pooled as compared with 40 16 of 40 patients for ustekinumab p 0 001 the percentage of patients with a 100 reduction in the pasi score was 45 in the pooled 90 mg and 180 mg risankizumab groups as compared with 18 in the ustekinumab group efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab in the 18 mg and 90 mg risankizumab groups and the ustekinumab group 5 patients 12 6 patients 15 and 3 patients 8 respectively had serious adverse events including two basal cell carcinomas and one major cardiovascular adverse event there were no serious adverse events in the 180 mg risankizumab group in this phase 2 trial selective blockade of interleukin 23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab this trial was not large enough or of long enough duration to draw conclusions about safety funded by boehringer ingelheim clinicaltrials gov number nct02054481.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28423301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2158, "text": "1 for adults with plaque psoriasis after failure of topical symptomatic treatments and puva therapy several systemic immunosuppressive agents are acceptable for severe disease methotrexate then ciclosporin and possible a tnf alpha antagonist etanercept etc 2 ustekinumab is an inhibitor of interleukins 12 and 23 which are believed to be implicated in the onset of psoriasis it is authorized in the european union for patients who fail to respond to conventional systemic treatments 3 in one trial with a low level of evidence single blind 2 subcutaneous injections of ustekinumab at an interval of 4 weeks appeared to be statistically more effective than twice weekly subcutaneous injections of etanercept for 12 weeks more patients achieved a 75 reduction in the score most widely used to evaluate the extent and intensity of plaque psoriasis lesions pasi score about 71 versus 57 the results beyond this period have not been reported 4 two randomised double blind placebo controlled trials in a total of 1996 patients showed that at least two thirds of patients treated with ustekinumab achieved at least a 75 reduction in their pasi score versus fewer than 4 with placebo 5 in animal studies interleukin 12 and 23 inhibitors cause cancer there is therefore a high risk of cancer developing during prolonged treatment with ustekinumab 6 the main adverse effects identified in clinical trials include infections injection site reactions psychological disorders and development of anti ustekinumab antibodies 7 there is insufficient follow up to evaluate the cardiac risks associated with ustekinumab 8 as maintenance therapy ustekinumab is administered as one subcutaneous injection every 12 weeks this practical advantage compared to tnf alpha antagonists must be weighed against the risks inherent in prolonged immunosuppression 9 in summary for symptomatic relief of patients whose psoriasis poses major problems despite treatment with methotrexate or ciclosporin in the absence of a better alternative it is better to use a tnf alpha antagonist and to avoid exposing patients to the risks associated with ustekinumab particularly its carcinogenic risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19882785", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2160, "text": "biologic agents offer a range of new therapeutic options for patients with psoriasis however the relative benefit risk profiles of such therapies are not well known we compared two biologic agents ustekinumab an interleukin 12 and interleukin 23 blocker and etanercept an inhibitor of tumor necrosis factor alpha for the treatment of psoriasis we randomly assigned 903 patients with moderate to severe psoriasis to receive subcutaneous injections of either 45 or 90 mg of ustekinumab at weeks 0 and 4 or high dose etanercept 50 mg twice weekly for 12 weeks the primary end point was the proportion of patients with at least 75 improvement in the psoriasis area and severity index pasi at week 12 a secondary end point was the proportion with cleared or minimal disease on the basis of the physician s global assessment assessors were unaware of the treatment assignments the efficacy and safety of a crossover from etanercept to ustekinumab were evaluated after week 12 there was at least 75 improvement in the pasi at week 12 in 67 5 of patients who received 45 mg of ustekinumab and 73 8 of patients who received 90 mg as compared with 56 8 of those who received etanercept p 0 01 and p 0 001 respectively similarly 65 1 of patients who received 45 mg of ustekinumab and 70 6 of patients who received 90 mg of ustekinumab had cleared or minimal disease according to the physician s global assessment as compared with 49 0 of those who received etanercept p 0 001 for both comparisons among patients who did not have a response to etanercept 48 9 had at least 75 improvement in the pasi within 12 weeks after crossover to ustekinumab one or more adverse events occurred through week 12 in 66 0 of patients who received 45 mg of ustekinumab and 69 2 of patients who received 90 mg of ustekinumab and in 70 0 who received etanercept 1 9 1 2 and 1 2 respectively had serious adverse events safety patterns were similar before and after crossover from etanercept to ustekinumab the efficacy of ustekinumab at a dose of 45 or 90 mg was superior to that of high dose etanercept over a 12 week period in patients with psoriasis clinicaltrials gov number nct00454584.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20071701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2109, "text": "repeated subcutaneous injections of a monoclonal antibody against the p40 subunit of interleukins 12 and 23 ustekinumab were used to treat patients with relapsing remitting multiple sclerosis rrms to assess the drug s safety efficacy and pharmacokinetics in this phase ii multicentre randomised double blind placebo controlled study 249 patients with rrms aged 18 65 years were eligible to be assigned equally by a central randomisation procedure based on study site and presence or absence of gadolinium enhancing t1 weighted lesions at baseline to one of five groups that received placebo or four different ustekinumab dosages at weeks 0 1 2 3 7 11 15 and 19 ustekinumab doses were 27 mg 90 mg q8w 90 mg or 180 mg the 90 mg q8w dosage group received placebo substitute at weeks 7 and 15 the primary endpoint was the cumulative number of new gadolinium enhancing t1 weighted lesions on serial cranial mri through week 23 patients were followed up through week 37 analysis was by intention to treat this trial is registered with clinicaltrials gov number nct00207727 from august 2004 to december 2006 249 patients underwent randomisation 49 for placebo 50 for each ustekinumab group ustekinumab treatment did not show a significant reduction in the primary endpoint for any dosage groups versus placebo at week 37 adverse events occurred in 38 78 placebo treated patients and 170 85 ustekinumab treated patients with infections most commonly reported serious adverse events occurred in one 2 placebo treated patient and six 3 ustekinumab treated patients malignant diseases were reported in two patients shortly after the initiation of ustekinumab treatment both patients were withdrawn from the trial and given appropriate treatment which resulted in complete remission no serious infections cardiovascular events or exacerbation of demyelinating events occurred a dose dependent increase in serum concentrations of ustekinumab was recorded ustekinumab is generally well tolerated but does not show efficacy in reducing the cumulative number of gadolinium enhancing t1 weighted lesions in multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18703004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1634, "text": "interleukin 12 and interleukin 23 are inflammatory cytokines implicated in crohn s disease pathophysiology ustekinumab is a monoclonal antibody against the p40 subunit of interleukin 12 23 we performed a double blind cross over trial of the clinical effects of ustekinumab in 104 patients with moderate to severe crohn s disease population 1 patients were given subcutaneous placebo at weeks 0 3 then ustekinumab at weeks 8 11 subcutaneous ustekinumab at weeks 0 3 then placebo at weeks 8 11 intravenous placebo at week 0 then ustekinumab at week 8 or intravenous ustekinumab at week 0 then placebo at week 8 furthermore an open label trial evaluated the effects of 4 weekly subcutaneous injections or 1 intravenous infusion of ustekinumab in 27 patients who were primary or secondary nonresponders to infliximab population 2 in population 1 clinical response rates for the combined groups given ustekinumab and placebo were 53 and 30 p 02 respectively at weeks 4 and 6 and 49 and 40 p 34 respectively at week 8 in a subgroup of 49 patients who were previously given infliximab neither primary nor secondary nonresponders clinical response to ustekinumab was significantly greater than the group given placebo p 05 through week 8 in population 2 the clinical responses at week 8 to subcutaneous and intravenous ustekinumab were 43 and 54 respectively there was no increase in the number of adverse or serious adverse events in patients given ustekinumab through week 8 compared with placebo ustekinumab induced a clinical response in patients with moderate to severe crohn s disease especially in patients previously given infliximab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18706417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "anti p40 antibodies ustekinumab and briakinumab blockade of interleukin 12 and interleukin 23 in the treatment of psoriasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20430307", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "efficacy and safety of ustekinumab a human interleukin 12 23 monoclonal antibody in patients with psoriasis 76 week results from a randomised double blind placebo controlled trial phoenix 1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18486739", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1116, "text": "ustekinumab is a fully human monoclonal antibody directed against the p40 subunit shared by interleukin 12 and interleukin 23 two naturally occurring protein regulators that play an important role in immune mediated inflammatory diseases including psoriatic arthritis psa in september of 2009 the us fda approved ustekinumab for the treatment of adult patients with moderate to severe plaque psoriasis beginning in november of 2009 janssen biotech formerly centocor biotech the developer of ustekinumab initiated clinical trials to investigate the efficacy of ustekinumab in the treatment of other inflammatory disorders including psa phase ii and phase iii studies showed both a good safety profile and significant efficacy for ustekinumab in the treatment of psa leading to the drug s approval in both europe and the usa in an immunotherapy market currently dominated by anti tnf \u03b1 drugs for the treatment of psa ustekinumab offers an alternative option for patients with psa including those unresponsive to methotrexate and the tnf \u03b1 inhibitory agents currently approved for this potentially debilitating disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24410536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1557, "text": "ustekinumab is a fully human monoclonal antibody that binds with high specificity and affinity to the cytokines interleukin il 12 and il 23 thereby suppressing il 12 and il 23 mediated inflammation associated with psoriasis in two large phase iii trials in patients with moderate to severe plaque psoriasis significantly more subcutaneous ustekinumab 45 or 90 mg recipients administered as two injections 4 weeks apart than placebo recipients achieved a 75 improvement on the psoriasis area and severity index pasi 75 score at 12 weeks other efficacy measures including the physician s global assessment of clinical response at week 12 also favored ustekinumab over placebo psoriatic symptom control was maintained during ustekinumab maintenance therapy administered once every 12 weeks for up to 76 weeks in a phase ii trial in patients with active plaque psoriasis and psoriatic arthritis signs and symptoms of arthritis and psoriatic symptom control were improved to a greater extent with ustekinumab than with placebo at 12 weeks based on the proportion of patients achieving a 20 improvement in american college of rheumatology response criteria arthritis or pasi 75 skin symptoms health related quality of life assessed using the dermatology life quality index and the health assessment questionnaire disability index was improved to a significantly greater extent with ustekinumab than with placebo at week 12 subcutaneous ustekinumab was generally well tolerated in clinical trials with most treatment emergent adverse events being of mild severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19344192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 883, "text": "the choice of therapeutic agents for patients with moderate to severe psoriasis has expanded significantly in the past decade with new understanding of the immunologic basis of psoriasis multiple new potential targets for therapy have been identified it is likely that a series of new medications to focus on the newly identified pathways is on the horizon the first pathway targeted by new medications focuses on the p40 subunit that is shared by interleukin il 12 and il 23 two human anti p40 antibodies have been used therapeutically in psoriasis to date ustekinumab cnto 1275 stelara centocor horsham pa and briakinumab abt 874 abbott abbott park il ustekinumab was recently approved by the united states food and drug administration making it the first medication approved in the united states to work by this pathway while briakinumab is currently in phase iii clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20430307", "endSection": "abstract" } ] }, { "body": "What is a potential side effect for Tymlos?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28389324", "http://www.ncbi.nlm.nih.gov/pubmed/28624872" ], "ideal_answer": [ "Possible bone cancer (osteosarcoma). During animal drug testing, TYMLOS caused some rats to develop a bone cancer called osteosarcoma." ], "exact_answer": [ "Osteosarcoma" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D064420", "https://meshb.nlm.nih.gov/record/ui?ui=D000069451" ], "type": "factoid", "id": "5a551a8fb750ff4455000002", "snippets": [ { "offsetInBeginSection": 1220, "offsetInEndSection": 1403, "text": "Thus, near life-long treatment with abaloparatide in rats resulted in dose and time dependent formation of osteosarcomas, with a comparable response to hPTH(1-34) at similar exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389324", "endSection": "abstract" } ] }, { "body": "Which disorder has been approved for treatment with Alk inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28669346", "http://www.ncbi.nlm.nih.gov/pubmed/27707887", "http://www.ncbi.nlm.nih.gov/pubmed/27865624", "http://www.ncbi.nlm.nih.gov/pubmed/28054318", "http://www.ncbi.nlm.nih.gov/pubmed/27545320", "http://www.ncbi.nlm.nih.gov/pubmed/27498387", "http://www.ncbi.nlm.nih.gov/pubmed/28050598" ], "ideal_answer": [ "Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer.", "Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011" ], "exact_answer": [ "ALK-positive lung cancer" ], "type": "factoid", "id": "5a87f44061bb38fb2400000f", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 144, "text": "Alectinib and crizotinib have been approved for the therapy of NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, is approved for treatment of patients with ALK+ non-small cell lung cancer who have progressed, on or are intolerant to, crizotinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27545320", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 340, "text": " Ceritinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the ALK gene rearrangement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27707887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28054318", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 702, "text": "Dramatic and often prolonged responses are seen in patients withALKalterations when treated with ALK inhibitors. Three of these-crizotinib, ceritinib, and alectinib-are now FDA approved for the treatment of metastatic NSCLC positive forALKfusions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28050598", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 809, "text": "In addition, novel ALKis exhibit good antitumor efficacy for brain metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27865624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Introduction Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28669346", "endSection": "abstract" }, { "offsetInBeginSection": 1807, "offsetInEndSection": 2013, "text": "Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28669346", "endSection": "abstract" } ] }, { "body": "List proteins that are targeted by \"immune checkpoints inhibitors\".", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28848698", "http://www.ncbi.nlm.nih.gov/pubmed/27471612", "http://www.ncbi.nlm.nih.gov/pubmed/28435391" ], "ideal_answer": [ "The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab." ], "exact_answer": [ [ "CTLA-4" ], [ "PD-1" ], [ "PD1-L" ] ], "type": "list", "id": "5a8842a261bb38fb24000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1 (PD-1) and anti-programmed cell death protein ligand 1 (PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer (NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28848698", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1435, "text": " S100A9-targeting agents with immune checkpoints inhibitors,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27471612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Programmed cell death 1 checkpoint inhibitors in the treatment of patients with advanced melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28435391", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 516, "text": "The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28435391", "endSection": "abstract" } ] }, { "body": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25577568", "http://www.ncbi.nlm.nih.gov/pubmed/19309453", "http://www.ncbi.nlm.nih.gov/pubmed/16478940", "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "http://www.ncbi.nlm.nih.gov/pubmed/16284307", "http://www.ncbi.nlm.nih.gov/pubmed/25145395", "http://www.ncbi.nlm.nih.gov/pubmed/28589936", "http://www.ncbi.nlm.nih.gov/pubmed/27049520", "http://www.ncbi.nlm.nih.gov/pubmed/27440550", "http://www.ncbi.nlm.nih.gov/pubmed/11752389", "http://www.ncbi.nlm.nih.gov/pubmed/22409484", "http://www.ncbi.nlm.nih.gov/pubmed/22368074", "http://www.ncbi.nlm.nih.gov/pubmed/17077182", "http://www.ncbi.nlm.nih.gov/pubmed/15546359", "http://www.ncbi.nlm.nih.gov/pubmed/16126837", "http://www.ncbi.nlm.nih.gov/pubmed/14742873" ], "ideal_answer": [ "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors", "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression", "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. Auxin enhances the binding of Aux/IAA proteins to the receptor TIR1, which is an F-box protein that is part of the E3 ubiquitin ligase complex SCF(TIR1).", "Auxin is sensed by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, which leads to IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Evidence also exists for SCF(TIR1)-mediated ubiquitination of the Aux/IAA proteins SHY2/IAA3 and BDL/IAA12", "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. Auxin dose-response assays revealed that IAA9 downregulated lines were hypersensitive to auxin, although the only early auxin-responsive gene that was found to be upregulated in the antisense lines was IAA3. We report here that the downregulation of IAA9, a tomato (Solanum lycopersicum) gene from a distinct subfamily of Aux/IAA genes, results in a pleiotropic phenotype, consistent with its ubiquitous expression pattern. While no mutation in any member of subfamily IV has been reported to date, the phenotypes associated with the downregulation of IAA9 reveal distinct and novel roles for members of the Aux/IAA gene family. Aux/IAA proteins are short-lived nuclear proteins that repress expression of primary/early auxin response genes in protoplast transfection assays. Here, we systematically dissect auxin sensing by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. Binding of Aux/IAA proteins leads to degradation via the 26S proteasome, but evidence for SCF(TIR1)-mediated poly-ubiquitination of Aux/IAA proteins is lacking. ", "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. The tomato Aux/IAA transcription factor IAA9 is involved in fruit development and leaf morphogenesis. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression. Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors. While no mutation in any member of subfamily IV has been reported to date, the phenotypes associated with the downregulation of IAA9 reveal distinct and novel roles for members of the Aux/IAA gene family. Nce for SCF-mediated ubiquitination of the Aux/IAA proteins SHY2/IAA3 and BDL/IAA12. Aux/IAA proteins are short-lived nuclear proteins that repress expression of primary/early auxin response genes in protoplast transfection assays. We showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Here, we systematically dissect auxin sensing by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. ", "Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors. The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression. The tomato Aux/IAA transcription factor IAA9 is involved in fruit development and leaf morphogenesis. Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. Here, we systematically dissect auxin sensing by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. We showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Auxin dose-response assays revealed that IAA9 downregulated lines were hypersensitive to auxin, although the only early auxin-responsive gene that was found to be upregulated in the antisense lines was IAA3. While no mutation in any member of subfamily IV has been reported to date, the phenotypes associated with the downregulation of IAA9 reveal distinct and novel roles for members of the Aux/IAA gene family. " ], "exact_answer": [ [ "IAA6", "IAA6" ], [ "IAA9", "IAA9" ], [ "IAA4" ], [ "SCIFTR1" ], [ "SHY2/IAA3", "IAA3" ], [ "BDL/IAA12", "IAA12" ] ], "type": "list", "id": "5a86c938faa1ab7d2e000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "endSection": "title" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1043, "text": "Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 380, "text": "Here, we systematically dissect auxin sensing by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589936", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1214, "text": "We showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25577568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Auxin-induced, SCF(TIR1)-mediated poly-ubiquitination marks AUX/IAA proteins for degradation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19309453", "endSection": "title" }, { "offsetInBeginSection": 716, "offsetInEndSection": 810, "text": "evidence for SCF(TIR1)-mediated ubiquitination of the Aux/IAA proteins SHY2/IAA3 and BDL/IAA12", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19309453", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 638, "text": "Auxin enhances the binding of Aux/IAA proteins to the receptor TIR1, which is an F-box protein that is part of the E3 ubiquitin ligase complex SCF(TIR1). Binding of Aux/IAA proteins leads to degradation via the 26S proteasome, but evidence for SCF(TIR1)-mediated poly-ubiquitination of Aux/IAA proteins is lacking", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19309453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The tomato Aux/IAA transcription factor IAA9 is involved in fruit development and leaf morphogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126837", "endSection": "title" }, { "offsetInBeginSection": 333, "offsetInEndSection": 547, "text": "We report here that the downregulation of IAA9, a tomato (Solanum lycopersicum) gene from a distinct subfamily of Aux/IAA genes, results in a pleiotropic phenotype, consistent with its ubiquitous expression pattern", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126837", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1182, "text": "Auxin dose-response assays revealed that IAA9 downregulated lines were hypersensitive to auxin, although the only early auxin-responsive gene that was found to be upregulated in the antisense lines was IAA3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126837", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1566, "text": "The activity of the IAA3 promoter was stimulated in the IAA9 antisense genetic background, indicating that IAA9 acts in planta as a transcriptional repressor of auxin signaling. While no mutation in any member of subfamily IV has been reported to date, the phenotypes associated with the downregulation of IAA9 reveal distinct and novel roles for members of the Aux/IAA gene family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Aux/IAA proteins are short-lived nuclear proteins that repress expression of primary/early auxin response genes in protoplast transfection assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14742873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "AUX/IAA proteins are active repressors, and their stability and activity are modulated by auxin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11752389", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 248, "text": "There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression [3].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 195, "text": "Functional characterization of SlIAA15, a member of the tomato (Solanum lycopersicum)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22409484", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 303, "text": "Functional characterization of SlIAA15, a member of the tomato (Solanum lycopersicum) Aux/IAA family, shows that the encoded protein acts as a strong repressor of auxin-dependent transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22409484", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 306, "text": "The Aux/IAA genes are best characterized among the early auxin-responsive genes, which encode short-lived transcriptional repressors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17077182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "plant stress tolerance requires auxin sensitive aux iaa transcriptional repressors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "genome wide analysis and characterization of aux iaa family genes in brassica rapa", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049520", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1465, "text": "the aux iaa proteins are auxin sensitive repressors that mediate diverse physiological and developmental processes in plants 1 2 there are 29 aux iaa genes in arabidopsis that exhibit unique but partially overlapping patterns of expression 3 although some studies have suggested that individual aux iaa genes have specialized function genetic analyses of the family have been limited by the scarcity of loss of function phenotypes 4 furthermore with a few exceptions our knowledge of the factors that regulate aux iaa expression is limited 1 5 we hypothesize that transcriptional control of aux iaa genes plays a central role in the establishment of the auxin signaling pathways that regulate organogenesis growth and environmental response here we describe a screen for transcription factors tfs that regulate the aux iaa genes we identify tfs from 38 families including 26 members of the dreb cbf family several dreb cbf tfs directly promote transcription of the iaa5 and iaa19 genes in response to abiotic stress recessive mutations in these iaa genes result in decreased tolerance to stress conditions demonstrating a role for auxin in abiotic stress our results demonstrate that stress pathways interact with the auxin gene regulatory network grn through transcription of the aux iaa genes we propose that the aux iaa genes function as hubs that integrate genetic and environmental information to achieve the appropriate developmental or physiological outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1381, "text": "auxin is a central hormone that exerts pleiotropic effects on plant growth including the development of roots shoots flowers and fruit the perception and signaling of the plant hormone auxin rely on the cooperative action of several components among which auxin indole 3 acetic acid aux iaa proteins play a pivotal role in this study we identified and comprehensively analyzed the entire aux iaa gene family in tomato solanum lycopersicum a reference species for solanaceae plants and the model plant for fleshy fruit development functional characterization using a dedicated single cell system revealed that tomato aux iaa proteins function as active repressors of auxin dependent gene transcription with however different aux iaa members displaying varying levels of repression phylogenetic analysis indicated that the aux iaa gene family is slightly contracted in tomato compared with arabidopsis with a lower representation of non canonical proteins sl iaa genes display distinctive expression pattern in different tomato organs and tissues and some of them display differential responses to auxin and ethylene suggesting that aux iaas may play a role in linking both hormone signaling pathways the data presented here shed more light on sl iaa genes and provides new leads towards the elucidation of their function during plant development and in mediating hormone cross talk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22368074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1411, "text": "the aux iaa genes encode a large family of short lived proteins known to regulate auxin signalling in plants functional characterization of sliaa15 a member of the tomato solanum lycopersicum aux iaa family shows that the encoded protein acts as a strong repressor of auxin dependent transcription the physiological significance of sliaa15 was addressed by a reverse genetics approach revealing that sliaa15 plays multiple roles in plant developmental processes the sliaa15 down regulated lines display lower trichome number reduced apical dominance with associated modified pattern of axillary shoot development increased lateral root formation and decreased fruit set moreover the leaves of sliaa15 inhibited plants are dark green and thick with larger pavement cells longer palisade cells and larger intercellular space of spongy mesophyll cells the sliaa15 suppressed plants exhibit a strong reduction in type i v and vi trichome formation suggesting that auxin dependent transcriptional regulation is required for trichome initiation concomitant with reduced trichome formation the expression of some r2r3 myb genes putatively involved in the control of trichome differentiation is altered these phenotypes uncover novel and specialized roles for aux iaas in plant developmental processes clearly indicating that members of the aux iaa gene family in tomato perform both overlapping and specific functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22409484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1949, "text": "auxins are the key players in plant growth development involving leaf formation phototropism root fruit and embryo development auxin indole 3 acetic acid aux iaa are early auxin response genes noted as transcriptional repressors in plant auxin signaling however many studies focus on aux arf gene families and much less is known about the aux iaa gene family in brassica rapa b rapa here we performed a comprehensive genome wide analysis and identified 55 aux iaa genes in b rapa using four conserved motifs of aux iaa family pf02309 chromosomal mapping of the b rapa aux iaa briaa genes facilitated understanding cluster rearrangement of the crucifer building blocks in the genome phylogenetic analysis of briaa with arabidopsis thaliana oryza sativa and zea mays identified 51 sister pairs including 15 same species briaa briaa and 36 cross species briaa atiaa iaa genes among the 55 briaa genes expression of 43 and 45 genes were verified using genebank b rapa ests and in home developed microarray data from mature leaves of chiifu and rcbr lines despite their huge morphological difference tissue specific expression analysis of briaa genes between the parental lines chiifu and rcbr showed that the genes followed a similar pattern of expression during leaf development and a different pattern during bud flower and siliqua development stages the response of the briaa genes to abiotic and auxin stress at different time intervals revealed their involvement in stress response single nucleotide polymorphisms between iaa genes of reference genome chiifu and rcbr were focused and identified our study examines the scope of conservation and divergence of aux iaa genes and their structures in b rapa analyzing the expression and structural variation between two parental lines will significantly contribute to functional genomics of brassica crops and we belive our study would provide a foundation in understanding the aux iaa genes in b rapa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1366, "text": "the plant hormone auxin plays a central role in regulating many aspects of plant growth and development this largely occurs as a consequence of changes in gene expression the aux iaa genes are best characterized among the early auxin responsive genes which encode short lived transcriptional repressors in most plants examined including arabidopsis soybean and rice the aux iaa genes constitute a large gene family by screening the available databases at least 15 expressed sequence tags ests have been identified from wheat triticum aestivum which exhibit high sequence identity with aux iaa homologues in other species one of these aux iaa genes taiaa1 harbouring all the four conserved domains characteristic of the aux iaa proteins has been characterized in detail the expression of taiaa1 is light sensitive tissue specific and is induced within 15 30 min of exogenous auxin application also the taiaa1 transcript levels increase in the presence of a divalent cation ca 2 and this effect is reversed by the calcium chelating agent egta the taiaa1 gene qualifies as the primary response gene because an increase in its transcript levels by auxin is unaffected by cycloheximide in addition to auxin the taiaa1 gene is also induced by brassinosteroid providing evidence that interplay between hormones is crucial for the regulation of plant growth and development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17077182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1497, "text": "auxin regulates various aspects of plant growth and development the auxin indole 3 acetic acid aux iaa genes encode short lived transcriptional repressors that are targeted by the transport inhibitor response1 auxin receptor f box proteins the aux iaa proteins regulate auxin mediated gene expression by interacting with members of the auxin response factor protein family aux iaa function is poorly understood herein we report the identification and characterization of insertion mutants in 12 of the 29 aux iaa family members the mutants show no visible developmental defects compared with the wild type double or triple mutants of closely related aux iaa genes such as iaa8 1 iaa9 1 or iaa5 1 iaa6 1 iaa19 1 also exhibit wild type phenotypes global gene expression analysis reveals that the molecular phenotypes of auxin treated and untreated light grown seedlings are unaffected in the iaa17 6 and iaa5 1 iaa6 1 iaa19 1 mutants by contrast similar analysis with the gain of function axr3 1 iaa17 1 mutant seedlings reveals dramatic changes in basal and auxin induced gene expression compared with the wild type expression of several type a arabidopsis response regulator genes and a number of genes involved in cell wall biosynthesis and degradation is repressed in axr3 1 iaa17 1 the data suggest extensive functional redundancy among aux iaa gene family members and that enhanced stability of the axr3 iaa17 protein severely alters the molecular phenotype resulting in developmental defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16284307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1413, "text": "the regulatory interactions between auxin response factors arfs and aux iaa repressors play a central role in auxin signal transduction yet the systems properties of this regulatory network are not well established we generated a steroid inducible arf5 monopteros mp transgenic background to survey the involvement of this factor in the transcriptional regulation of the entire aux iaa family in arabidopsis thaliana target genes of arf5 mp identified by this approach were confirmed by chromatin immunoprecipitation in vitro gel retardation assays and gene expression analyses our study shows that arf5 mp is indispensable for the correct regulation of nearly one half of all aux iaa genes and that these targets coincide with distinct subclades further genetic analyses demonstrate that the protein products of multiple aux iaa targets negatively feed back onto arf5 mp activity this work indicates that arf5 mp broadly influences the expression of the aux iaa gene family and suggests that such regulation involves the activation of specific subsets of redundantly functioning factors these groups of factors may then act together to control various processes within the plant through negative feedback on arf5 similar detailed analyses of other aux iaa arf regulatory modules will be required to fully understand how auxin signal transduction influences virtually every aspect of plant growth and development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25145395", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1750, "text": "a well known physiological adaptation process of plants encountering drying soil is to achieve water balance by reducing shoot growth and maintaining or promoting root elongation but little is known about the molecular basis of this process this study investigated the role of a drought up regulated triticum aestivum nac69 1 tanac69 1 in the modulation of root growth in wheat tanac69 1 was predominantly expressed in wheat roots at the early vegetative stage overexpression of tanac69 1 in wheat roots using osrsp3 essentially root specific and ospip2 3 root predominant promoters resulted in enhanced primary seminal root length and a marked increase in maturity root biomass competitive growth analysis under water limited conditions showed that osrsp3 promoter driven tanac69 1 transgenic lines produced 32 and 35 more above ground biomass and grains than wild type plants respectively tanac69 1 overexpression in the roots down regulated the expression of tashy2 and taiaa7 which are from the auxin iaa aux iaa transcriptional repressor gene family and are the homologs of negative root growth regulators shy2 iaa3 and iaa7 in arabidopsis the expression of tashy2 and taiaa7 in roots was down regulated by drought stress and up regulated by cytokinin treatment which inhibited root growth dna binding and transient expression analyses revealed that tanac69 1 bound to the promoters of tashy2 and taiaa7 acted as a transcriptional repressor and repressed the expression of reporter genes driven by the tashy2 or taiaa7 promoter these data suggest that tanac69 1 is a transcriptional repressor of tashy2 and taiaa7 homologous to arabidopsis negative root growth regulators and is likely to be involved in promoting root elongation in drying soil.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 861, "text": "auxin mediates numerous plant responses some of which have been shown to require transcriptional regulation one auxin response pathway which depends on the relief of transcriptional repression is mediated by tir1 transport inhibitor response protein 1 tir1 is an auxin receptor and also a subunit of an scf type ubiquitin ligase in the presence of a low concentration of auxin in the nucleus members of the aux iaa family of transcriptional repressors bind to arf proteins and inhibit the transcription of specific auxin response genes increased nuclear concentrations of auxin promote auxin binding to tir1 causing the aux iaa proteins to associate with tir1 and leading to their degradation by a proteasome mediated pathway this decreases the concentration of aux iaa proteins in the nucleus and thereby enables the expression of certain auxin response genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16478940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1465, "text": "recent studies of auxin response have focused on the functions of three sets of proteins the auxin aux response factors arfs the aux iaas and the f box protein tir1 the arf proteins bind dna and directly activate or repress transcription of target genes while the aux iaa proteins repress arf function tir1 is part of a ubiquitin protein ligase required for degradation of aux iaa proteins here we report the isolation and characterization of a novel mutant of arabidopsis called axr5 1 mutant plants are resistant to auxin and display a variety of auxin related growth defects including defects in root and shoot tropisms further the axr5 1 mutation results in a decrease in auxin regulated transcription the molecular cloning of axr5 revealed that the gene encodes the iaa1 protein a member of the aux iaa family of proteins axr5 is expressed throughout plant development consistent with the pleiotropic mutant phenotype the axr5 1 mutation results in an amino acid substitution in conserved domain ii of the protein similar to gain of function mutations recovered in other members of this gene family biochemical studies show that iaa1 axr5 interacts with tir1 in an auxin dependent manner the mutation prevents this interaction suggesting that the mutant phenotype is caused by the accumulation of iaa1 axr5 our results provide further support for a model in which most members of the aux iaa family are targeted for degradation by scftir1 in response to auxin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15546359", "endSection": "abstract" } ] }, { "body": "What is GenomeVIP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28522612" ], "ideal_answer": [ "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure.GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface.", "The Genome Variant Investigation Platform (GenomeVIP) is an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface.", "Genome Variant Investigation Platform (GenomeVIP) is an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure.", "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface.", "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. " ], "type": "summary", "id": "5a67c284b750ff4455000011", "snippets": [ { "offsetInBeginSection": 569, "offsetInEndSection": 1018, "text": "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 789, "text": "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 919, "text": "GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1422, "text": "Here, we demonstrate GenomeVIP's ability to provide high-confidence annotated somatic, germline, and de novo variants of potential biological significance using publicly available data sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1231, "text": "GenomeVIP has been used for genomic analysis in large-data projects such as the TCGA PanCanAtlas and in other projects, such as the ICGC Pilots, CPTAC, ICGC-TCGA DREAM Challenges, and the 1000 Genomes SV Project.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 1018, "text": "GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "GenomeVIP: a cloud platform for genomic variant discovery and interpretation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "GenomeVIP: a cloud platform for genomic variant discovery and interpretation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "title" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1423, "text": "Here, we demonstrate GenomeVIP's ability to provide high-confidence annotated somatic, germline, and de novo variants of potential biological significance using publicly available data sets..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1426, "text": "Here, we demonstrate GenomeVIP's ability to provide high-confidence annotated somatic, germline, and de novo variants of potential biological significance using publicly available data sets.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28522612", "endSection": "abstract" } ] }, { "body": "List the ten types of conjoined twins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1412053", "http://www.ncbi.nlm.nih.gov/pubmed/27369817", "http://www.ncbi.nlm.nih.gov/pubmed/25599848", "http://www.ncbi.nlm.nih.gov/pubmed/17049247", "http://www.ncbi.nlm.nih.gov/pubmed/12483645", "http://www.ncbi.nlm.nih.gov/pubmed/3267350", "http://www.ncbi.nlm.nih.gov/pubmed/26063696", "http://www.ncbi.nlm.nih.gov/pubmed/7866063", "http://www.ncbi.nlm.nih.gov/pubmed/23733407", "http://www.ncbi.nlm.nih.gov/pubmed/2754585", "http://www.ncbi.nlm.nih.gov/pubmed/7112433", "http://www.ncbi.nlm.nih.gov/pubmed/9951179", "http://www.ncbi.nlm.nih.gov/pubmed/15278382", "http://www.ncbi.nlm.nih.gov/pubmed/15278384", "http://www.ncbi.nlm.nih.gov/pubmed/21433086", "http://www.ncbi.nlm.nih.gov/pubmed/29064095", "http://www.ncbi.nlm.nih.gov/pubmed/23154370", "http://www.ncbi.nlm.nih.gov/pubmed/7469832", "http://www.ncbi.nlm.nih.gov/pubmed/16597654", "http://www.ncbi.nlm.nih.gov/pubmed/1031540", "http://www.ncbi.nlm.nih.gov/pubmed/21860927", "http://www.ncbi.nlm.nih.gov/pubmed/19429398", "http://www.ncbi.nlm.nih.gov/pubmed/27151716", "http://www.ncbi.nlm.nih.gov/pubmed/23771470", "http://www.ncbi.nlm.nih.gov/pubmed/16122113", "http://www.ncbi.nlm.nih.gov/pubmed/21660094", "http://www.ncbi.nlm.nih.gov/pubmed/28191207" ], "ideal_answer": [ "Thoraco-omphalopagus: Two bodies fused from the upper chest to the lower chest. These twins usually share a heart, and may also share the liver or part of the digestive system.\nThoracopagus:Two bodies fused from the upper thorax to lower belly. The heart is always involved in these cases.\nOmphalopagus: Two bodies fused at the lower abdomen. Unlike thoracopagus, the heart is never involved in these cases.\nPyopagus: joined at the buttocks with sacrum and coccyx anomalies\nRachipagus: Joined at the spine with vertebral and neural tube defects\nIschiopagus: joined at the hip from umbilicus to conjoined pelvis\nParasitic twins: Twins that are asymmetrically conjoined, resulting in one twin that is small, less formed, and dependent on the larger twin for survival.\nCraniopagus: Fused skulls, but separate bodies\nCephalopagus: head but not face or foramen magnum, brains are usually separate\nDicephalus dipus dibrachius: 2 heads and one body" ], "exact_answer": [ [ "Thoraco-omphalopagus" ], [ "Thoracopagus" ], [ "Omphalopagus" ], [ "Pyopagus" ], [ "Craniopagus" ], [ "Parasitic" ], [ "Rachipagus" ], [ "Ischiopagus" ], [ "diprosopus" ], [ "Dicephalus dipus dibrachius" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014428" ], "type": "list", "id": "5a76018c83b0d9ea6600000e", "snippets": [ { "offsetInBeginSection": 31, "offsetInEndSection": 81, "text": "Separation of Thoracoomphalopagus Conjoined Twins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27369817", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 235, "text": " Eight different types of conjoined twins have been described in the literature. M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29064095", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 234, "text": "Pygopagus are one of the rare types of conjoined twins with only a handful of cases reported in the literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25599848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Ischiopagus and diprosopus in India: two pairs of conjoined twins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23733407", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Dicephalus dipus dibrachius: conjoined twins ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28191207", "endSection": "title" }, { "offsetInBeginSection": 44, "offsetInEndSection": 135, "text": "conjoined tripus twins with features of rachipagus, parapagus dicephalus, and cephalopagus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21433086", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 40, "text": "craniopagus conjoined twin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154370", "endSection": "title" }, { "offsetInBeginSection": 436, "offsetInEndSection": 479, "text": "diagnosis of conjoined twins, thoracopagus,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21660094", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 280, "text": "Eight different types of conjoined twins can be distinguished; one is cephalopagus, which is fourth in rarity of occurrence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19429398", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 166, "text": "They are classified into eight different subtypes, with 18% representing pyopagus conjoints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17049247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Craniopagus twins (CPT) are an uncommon, highly fascinating accident of nature", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16597654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Ischiopagus and pygopagus conjoined twins:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15278384", "endSection": "title" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1172, "text": "The most common varieties encountered were thoraco-omphalopagus (28%), thoracopagus (18.5%), omphalopagus (10%), parasitic twins (10%) and craniopagus (6%)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15278382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Dicephalus dipus tetrabrachius conjoined twins of Zaria: case report and literature review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23771470", "endSection": "title" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1344, "text": "These anterolaterally united parapagus twins must result from two nearly parallel notochords in close proximity; craniopagi and pygopagi from fusion at the cranial and caudal neuropores, respectively; cephalopagi and ischiopagi from union at the pharyngeal and cloacal membranes, respectively; thoracopagi from merging of the cardiac anlage; and omphalopagi from fusion of the umbilicus or of the edges of two embryonic discs in any area not including the above sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1412053", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1174, "text": "The most common varieties encountered were thoraco-omphalopagus (28%), thoracopagus (18.5%), omphalopagus (10%), parasitic twins (10%) and craniopagus (6%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15278382", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 712, "text": "The most common types of conjoined twins were thoracoomphalopagus (28%), thoracopagus (18%), omphalopagus (10%), parasitic twins (10%), and craniopagus (6%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7112433", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 716, "text": "RESULTS Three sets of female conjoined twins underwent successful separation 2 pygopagus, one ischiopagus tripus) with 5 surviving infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12483645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Craniopagus-type conjoined twins (joined at the head) are exceedingly rare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26063696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Cephalopagus is a rare variety of conjoined twins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27151716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Magnetic resonance imaging (MRI) was used for the first time in the preoperative planning for separation of conjoined twins. In these omphalopagus infants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2754585", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 223, "text": "Cephalothoracopagus janiceps is a prototype of facing anomaly in which the two bodies demonstrated a cross symmetry to the midline,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3267350", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 512, "text": " Dicephalus dipus dibrachius is a case of side-by-side union, in which the bodies facing nearly the same direction were symmetrical to the middle sagittal plane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3267350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Frequency of thoracoomphalopagus conjoined twins in Thailand.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1031540", "endSection": "title" }, { "offsetInBeginSection": 606, "offsetInEndSection": 806, "text": "Forty cases of conjoined twins were included in the study. There were 72.5% cases of thoracophagus, 12.5% of paraphagus, 7.5% of omphalo-ischiophagus, 5.0% of omphalophagus, and 2.5% of cephalophagus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21860927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Dicephalus is one of the rarest types of conjoined twins. In such cases, the twins are usually stillborn or die shortly after birth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7866063", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 492, "text": "There were five omphalopagus, two pygopagus, two heterpagus and one ishiopagus twins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16122113", "endSection": "abstract" } ] }, { "body": "Which algorithm has been developed in order to improve multiple circular sequence alignment using refined sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28088189" ], "ideal_answer": [ "MARS improves multiple circular sequence alignment using refined sequences. MARS was implemented in the C++ programming language as a program to compute the rotations (cyclic shifts) required to best align a set of input sequences. Experimental results, using real and synthetic data, show that MARS improves the alignments, with respect to standard genetic measures and the inferred maximum-likelihood-based phylogenies, and outperforms state-of-the-art methods both in terms of accuracy and efficiency." ], "exact_answer": [ "MARS" ], "type": "factoid", "id": "5a6a3464b750ff4455000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "MARS: improving multiple circular sequence alignment using refined sequences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "title" }, { "offsetInBeginSection": 924, "offsetInEndSection": 1725, "text": "We present MARS, a new heuristic method for improving Multiple circular sequence Alignment using Refined Sequences. MARS was implemented in the C++ programming language as a program to compute the rotations (cyclic shifts) required to best align a set of input sequences. Experimental results, using real and synthetic data, show that MARS improves the alignments, with respect to standard genetic measures and the inferred maximum-likelihood-based phylogenies, and outperforms state-of-the-art methods both in terms of accuracy and efficiency. Our results show, among others, that the average pairwise distance in the multiple sequence alignment of a dataset of widely-studied mitochondrial DNA sequences is reduced by around 5% when MARS is applied before a multiple sequence alignment is performed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1019, "text": "We present MARS, a new heuristic method for improving Multiple circular sequence Alignment using Refined Sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1448, "text": "Experimental results, using real and synthetic data, show that MARS improves the alignments, with respect to standard genetic measures and the inferred maximum-likelihood-based phylogenies, and outperforms state-of-the-art methods both in terms of accuracy and efficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1040, "text": "RESULTS We present MARS, a new heuristic method for improving Multiple circular sequence Alignment using Refined Sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 1057, "text": "A solution for these inconsistencies would be to identify a suitable rotation (cyclic shift) for each sequence; these refined sequences may in turn lead to improved multiple sequence alignments using the preferred multiple sequence alignment program.
RESULTS: We present MARS, a new heuristic method for improving Multiple circular sequence Alignment using Refined Sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1213, "text": "MARS was implemented in the C++ programming language as a program to compute the rotations (cyclic shifts) required to best align a set of input sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "MARS: improving multiple circular sequence alignment using refined sequences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088189", "endSection": "title" } ] }, { "body": "Which stapled peptide has been designed to target Ctf4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28815832" ], "ideal_answer": [ "The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase\u2005\u03b1 from the replisome in yeast extracts." ], "exact_answer": [ "The stapled Sld5 peptide" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D010455", "http://www.biosemantics.org/jochem#4265011" ], "type": "factoid", "id": "5a6d08d5b750ff445500002c", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 999, "text": "The Ctf4/AND-1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the synthetic lethality approach. Herein, we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. By screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, submicromolar binding to Ctf4. The mode of interaction with Ctf4 was confirmed by a crystal structure of the stapled Sld5 peptide bound to Ctf4. The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase\u2005\u03b1 from the replisome in yeast extracts. Our study provides proof-of-principle evidence for the development of small-molecule inhibitors of the human CTF4 orthologue AND-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28815832", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 490, "text": "Herein, we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28815832", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 867, "text": "The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase\u2005\u03b1 from the replisome in yeast extracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28815832", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 635, "text": "By screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, submicromolar binding to Ctf4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28815832", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 870, "text": "The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase\u2005\u03b1 from the replisome in yeast extracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28815832", "endSection": "abstract" } ] }, { "body": "Mutation of which gene causes arterial tortuosity syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25373504", "http://www.ncbi.nlm.nih.gov/pubmed/28726533", "http://www.ncbi.nlm.nih.gov/pubmed/22116938", "http://www.ncbi.nlm.nih.gov/pubmed/26376865", "http://www.ncbi.nlm.nih.gov/pubmed/26398550" ], "ideal_answer": [ "Arterial tortuosity syndrome is an autosomal recessive connective tissue disorder caused by loss-of-function mutations in SLC2A10, which encodes facilitative glucose transporter 10 (GLUT10)." ], "exact_answer": [ "SLC2A10" ], "type": "factoid", "id": "5a70d42899e2c3af26000002", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 282, "text": "Mutations in SLC2A10, a gene that encodes the facilitative glucose transporter GLUT10, cause ATS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28726533", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 623, "text": "RECENT FINDINGS: Although arterial tortuosity has been primarily described in Loeys-Dietz syndrome due to TGFBR1 and TGFBR2 mutations and in arterial tortuosity syndrome due to SLC210A mutations, recent studies that use quantitative measures of tortuosity suggest that tortuosity is present in many other genetic conditions associated with aortic dilation and dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26398550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder caused by loss-of-function mutations in SLC2A10, which encodes facilitative glucose transporter 10 (GLUT10).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26376865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25373504", "endSection": "title" }, { "offsetInBeginSection": 651, "offsetInEndSection": 880, "text": "ATS is caused by mutations in the SLC2A10 gene, which encodes the facilitative glucose transporter 10 (GLUT10). Approximately 100 ATS patients have been described, and 21 causal mutations have been identified in the SLC2A10 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25373504", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 348, "text": "Mutations in SLC2A10/GLUT10, a member of the facilitative glucose transporter family, are associated with altered transforming growth factor-\u03b2 (TGF\u03b2) signaling in patients with arterial tortuosity syndrome (ATS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22116938", "endSection": "abstract" } ] }, { "body": "Fusarium oxysporum f. sp lycopersici. is a plant pathogen in plants producing what common food?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17022176", "http://www.ncbi.nlm.nih.gov/pubmed/16042017", "http://www.ncbi.nlm.nih.gov/pubmed/28683401", "http://www.ncbi.nlm.nih.gov/pubmed/9237400", "http://www.ncbi.nlm.nih.gov/pubmed/18624637", "http://www.ncbi.nlm.nih.gov/pubmed/23997634", "http://www.ncbi.nlm.nih.gov/pubmed/28549197", "http://www.ncbi.nlm.nih.gov/pubmed/24909710", "http://www.ncbi.nlm.nih.gov/pubmed/21942452", "http://www.ncbi.nlm.nih.gov/pubmed/24561899", "http://www.ncbi.nlm.nih.gov/pubmed/21053907", "http://www.ncbi.nlm.nih.gov/pubmed/28605157", "http://www.ncbi.nlm.nih.gov/pubmed/24313955", "http://www.ncbi.nlm.nih.gov/pubmed/18943372", "http://www.ncbi.nlm.nih.gov/pubmed/26810104", "http://www.ncbi.nlm.nih.gov/pubmed/28323535", "http://www.ncbi.nlm.nih.gov/pubmed/17408002" ], "ideal_answer": [ "Fusarium oxysporum f. sp lycopersici.produces causes vascular wilt disease in tomatoes.", "Fusarium wilt caused by Fusarium oxysporum f. sp lycopersici (Fol) is one of the main diseases affecting tomatoes. " ], "exact_answer": [ "Tomato" ], "type": "factoid", "id": "5a8b1264fcd1d6a10c00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The Fusarium wilt caused by Fusarium oxysporum strains is the most devastating disease of cucumber, banana, and tomato. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26810104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Seventy-four Fusarium oxysporum soil isolates were assayed for known effector genes present in an F. oxysporum f. sp. lycopersici race 3 tomato wilt strain (FOL MN-25) obtained from the same fields in Manatee County", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28323535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Fusarium wilt caused by Fusarium oxysporum f. sp lycopersici (Fol) is one of the main diseases affecting tomatoes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28549197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Fusarium wilt is one of the most prevalent and damaging diseases of tomato. Among various toxins secreted by the Fusarium oxysporum f. sp. lycopersici (causal agent of Fusarium wilt of tomato)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "In vitro antifugal activity of medicinal plant extract against Fusarium oxysporum f. sp. lycopersici race 3 the causal agent of tomato wilt.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24561899", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Inhibitory Effect of Algal Extracts on Mycelial Growth of the Tomato-Wilt Pathogen, Fusarium oxysporum f. sp. lycopersici.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997634", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The present study was undertaken to explore the inhibitory effect of cyanobacterial extracts of Nostoc commune FA-103 against the tomato-wilt pathogen, Fusarium oxysporum f. sp. lycopersici.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997634", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 404, "text": " we focused on the tomato (Solanum lycopersicum) and its pathogenic F. oxysporum f. sp. lycopersici (FOL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909710", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 253, "text": "Fusarium wilt of tomato caused by F. oxysporum f. sp. lycopersici. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17408002", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 182, "text": "Fusarium oxysporum f. sp. lycopersici is the causal agent of Fusarium wilt disease in tomato. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24313955", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 77, "text": "tomato pathogen Fusarium oxysporum f. sp. radicis-lycopersici ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17022176", "endSection": "title" }, { "offsetInBeginSection": 39, "offsetInEndSection": 100, "text": " vascular wilt pathogen Fusarium oxysporum f. sp. lycopersici", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21942452", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 114, "text": "Fusarium oxysporum f. sp. radicis-lycopersici, the causal agent of Fusarium crown and root rot of tomato,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18943372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The soilborne fungus Fusarium oxysporum f. sp. radicis-lycopersici causes tomato foot and root rot (TFRR), which can be controlled by the addition of the nonpathogenic fungus F. oxysporum Fo47 to the soil", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16042017", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 169, "text": "Fusarium oxysporum f. sp lycopersici, a tomato pathogen,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18624637", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 224, "text": "Fusarium oxysporum f. sp. lycopersici, a vascular pathogen of tomato, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9237400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "The purpose of this work was to gain an insight on the potential role of the phytopathogenic fungus Fusarium oxysporum f. sp. lycopersici in the translocation of metals and metalloids from soil to plant roots in tomato (Lycopersicum esculentum)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21053907", "endSection": "abstract" } ] }, { "body": "Is cilengitide effective for treatment of glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26918452", "http://www.ncbi.nlm.nih.gov/pubmed/28514722", "http://www.ncbi.nlm.nih.gov/pubmed/24442484", "http://www.ncbi.nlm.nih.gov/pubmed/25163906", "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "http://www.ncbi.nlm.nih.gov/pubmed/26792571", "http://www.ncbi.nlm.nih.gov/pubmed/28643756", "http://www.ncbi.nlm.nih.gov/pubmed/26717039", "http://www.ncbi.nlm.nih.gov/pubmed/27296952", "http://www.ncbi.nlm.nih.gov/pubmed/26935578" ], "ideal_answer": [ "No, cilengitide does not improve survival of glioblastoma (GBM) patients. Cilengitide is a cyclic pentapeptide that demonstrated efficacy for GBM treatment by targeting the integrins av\u03b23 and av\u03b25 over-expressed on GBM cells. However, randomized phase III CENTRIC and phase II CORE trials explored failed to meet their primary endpoints. However, in CORE, higher \u03b1v\u03b23 levels in tumor cells were associated with improved progression-free survival by central review and with improved overall survival in patients treated with cilengitide. Analysis of randomized clinical trials of antiangiogenic drugs (including cilengitide) showed no improvement in overall survival and a trend for an inferior outcome, in terms of overall survival, in patients receiving antiangiogenic drug alone compared to cytotoxic drug alone." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D005909", "https://meshb.nlm.nih.gov/record/ui?ui=D016896", "http://www.biosemantics.org/jochem#4242009" ], "type": "yesno", "id": "5a76080683b0d9ea66000015", "snippets": [ { "offsetInBeginSection": 542, "offsetInEndSection": 1013, "text": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "endSection": "abstract" }, { "offsetInBeginSection": 1713, "offsetInEndSection": 1878, "text": "However, we could not conclusively confirm whether cilengitide 2000mg/5/week was the optimum regime, as only one trial using this protocol was included in our study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28514722", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 254, "text": "Cilengitide (CGT) is a cyclic pentapeptide that demonstrated efficacy for GBM treatment by targeting the integrins av\u03b23 and av\u03b25 over-expressed on GBM cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26792571", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 842, "text": "Cilengitide is recently failed in Phase III CENTRIC trial in unselected patients with GBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26717039", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1432, "text": "In conclusion, we demonstrate that EGFRvIII/integrin \u03b23 complexes promote GBM progression and metastasis in the environment of hypoxia and vitronectin-enrichment, and cilengitide may serve as a promising therapeutics for EGFRvIII-positive GBMs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26717039", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1442, "text": "he addition of molecularly targeted drugs to TEM\u2009+\u2009RAD did not improve the OS of patients with GBM; however, it did improve PFS in patients treated by cilengitide who could not get improvement in OS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296952", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 449, "text": " The randomized phase III CENTRIC and phase II CORE trials explored the integrin inhibitor cilengitide in patients with newly diagnosed glioblastoma with versus without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. These trials failed to meet their primary endpoints", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26918452", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1106, "text": ". In CORE, higher \u03b1v\u03b23 levels in tumor cells were associated with improved progression-free survival by central review and with improved overall survival in patients treated with cilengitide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26918452", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1461, "text": "Cilengitide combined with metronomic temozolomide and procarbazine in MGMT-promoter unmethylated glioblastoma did not improve survival compared with historical data and does not warrant further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26935578", "endSection": "abstract" }, { "offsetInBeginSection": 2477, "offsetInEndSection": 2629, "text": "The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25163906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24442484", "endSection": "title" }, { "offsetInBeginSection": 1525, "offsetInEndSection": 1702, "text": "It may be proposed that the combination therapy of NG2 suppression and cilengitide treatment showed no considerable effect on glioblastoma compared to cilengitide therapy alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28643756", "endSection": "abstract" } ] }, { "body": "What is BBCAnalyzer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28241736" ], "ideal_answer": [ "BBCAnalyzer (Bases By CIGAR Analyzer) provides a novel visual approach to facilitate this step of time-consuming, manual inspection of common mutation sites. BBCAnalyzer is able to visualize base counts at predefined positions or regions in any sequence alignment data that are available as BAM files. Thereby, the tool provides a straightforward solution for evaluating any list of expected mutations like hotspot mutations, or even whole regions of interest. In addition to an ordinary textual report, BBCAnalyzer reports highly customizable plots. Information on the counted number of bases, the reference bases, known mutations or polymorphisms, called mutations and base qualities is summarized in a single plot. By uniting this information in a graphical way, the user may easily decide on a variant being present or not - completely independent of any internal filters or frequency thresholds." ], "type": "summary", "id": "5a6e3d21b750ff4455000043", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "BBCAnalyzer: a visual approach to facilitate variant calling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "title" }, { "offsetInBeginSection": 508, "offsetInEndSection": 1408, "text": "BBCAnalyzer (Bases By CIGAR Analyzer) provides a novel visual approach to facilitate this step of time-consuming, manual inspection of common mutation sites. BBCAnalyzer is able to visualize base counts at predefined positions or regions in any sequence alignment data that are available as BAM files. Thereby, the tool provides a straightforward solution for evaluating any list of expected mutations like hotspot mutations, or even whole regions of interest. In addition to an ordinary textual report, BBCAnalyzer reports highly customizable plots. Information on the counted number of bases, the reference bases, known mutations or polymorphisms, called mutations and base qualities is summarized in a single plot. By uniting this information in a graphical way, the user may easily decide on a variant being present or not - completely independent of any internal filters or frequency thresholds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1606, "text": "BBCAnalyzer provides a unique, novel approach to facilitate variant calling where classical tools frequently fail to call. The R package is freely available at http://bioconductor.org .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 789, "text": "BBCAnalyzer is able to visualize base counts at predefined positions or regions in any sequence alignment data that are available as BAM files.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 645, "text": "BBCAnalyzer (Bases By CIGAR Analyzer) provides a novel visual approach to facilitate this step of time-consuming, manual inspection of common mutation sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1511, "text": "BBCAnalyzer provides a unique, novel approach to facilitate variant calling where classical tools frequently fail to call.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1572, "text": "By uniting this information in a graphical way, the user may easily decide on a variant being present or not - completely independent of any internal filters or frequency thresholds.
CONCLUSIONS: BBCAnalyzer provides a unique, novel approach to facilitate variant calling where classical tools frequently fail to call.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 683, "text": "hotspot mutations), that have not been called by the software, need to be investigated manually.
RESULTS: BBCAnalyzer (Bases By CIGAR Analyzer) provides a novel visual approach to facilitate this step of time-consuming, manual inspection of common mutation sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 666, "text": "BBCAnalyzer (Bases By CIGAR Analyzer) provides a novel visual approach to facilitate this step of time-consuming, manual inspection of common mutation sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1545, "text": "BBCAnalyzer provides a unique, novel approach to facilitate variant calling where classical tools frequently fail to call.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 810, "text": "BBCAnalyzer is able to visualize base counts at predefined positions or regions in any sequence alignment data that are available as BAM files.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 666, "text": "RESULTS BBCAnalyzer (Bases By CIGAR Analyzer) provides a novel visual approach to facilitate this step of time-consuming, manual inspection of common mutation sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1546, "text": "CONCLUSIONS BBCAnalyzer provides a unique, novel approach to facilitate variant calling where classical tools frequently fail to call.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "BBCAnalyzer: a visual approach to facilitate variant calling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241736", "endSection": "title" } ] }, { "body": "Can multiple myeloma patients develop hyperviscosity syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27079282", "http://www.ncbi.nlm.nih.gov/pubmed/26623375", "http://www.ncbi.nlm.nih.gov/pubmed/25383860", "http://www.ncbi.nlm.nih.gov/pubmed/29159010", "http://www.ncbi.nlm.nih.gov/pubmed/7699907", "http://www.ncbi.nlm.nih.gov/pubmed/2385441", "http://www.ncbi.nlm.nih.gov/pubmed/29136724", "http://www.ncbi.nlm.nih.gov/pubmed/28983379", "http://www.ncbi.nlm.nih.gov/pubmed/6155195", "http://www.ncbi.nlm.nih.gov/pubmed/9046114", "http://www.ncbi.nlm.nih.gov/pubmed/28116769", "http://www.ncbi.nlm.nih.gov/pubmed/26181153", "http://www.ncbi.nlm.nih.gov/pubmed/25778852", "http://www.ncbi.nlm.nih.gov/pubmed/28550239" ], "ideal_answer": [ "Yes, multiple myeloma patients can develop hyperviscosity syndrome. Multiple myeloma is a neoplastic plasma-cell disorder resulting from malignant plasma cells in the bone marrow. It can cause a hyperviscosity syndrome secondary to the paraproteinaemia associated with the disease. The increased hyperviscosity can lead to retinal vein occlusions and other ocular problems." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D009101", "http://www.disease-ontology.org/api/metadata/DOID:9538" ], "type": "yesno", "id": "5a6f829eb750ff4455000054", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Multiple myeloma (MM) is an immedicable malignancy of the human plasma cells producing abnormal antibodies (also referred to as paraproteins) leading to kidney problems and hyperviscosity syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116769", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 594, "text": "This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28550239", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 589, "text": " A 73-year-old woman with known MM who received little treatment for several years, presented secondary to dysarthria and at first was thought to have hyperviscosity syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28983379", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 929, "text": " After a comprehensive evaluation ruled out common causes of acute renal failure, the patient underwent testing with a bone survey, urine protein electrophoresis (UPEP), serum protein electrophoresis (SPEP), and immunoelectrophoresis for suspected plasma cell dyscrasia and received plasmapheresis for hyperviscosity syndrome and nephrotoxicity, which resulted in improved renal function. Lab results showed monoclonal gammopathy, elevated serum free light chains, and Bence Jones protein in the urine with a follow-up bone marrow biopsy indicating plasma cell dyscrasia. The patient received a diagnosis of multiple myeloma (MM) and was started on chemotherapy and immunosuppression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29159010", "endSection": "abstract" }, { "offsetInBeginSection": 2611, "offsetInEndSection": 2781, "text": "Plasmapheresis (PE) is recommended for patients with hyperviscosity syndrome or cast nephropathy presented with AKI, which may help to increase the dialysis-independency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Multiple myeloma is a neoplastic plasma-cell disorder resulting from malignant plasma cells in the bone marrow. It can cause a hyperviscosity syndrome secondary to the paraproteinaemia associated with the disease. The increased hyperviscosity can lead to retinal vein occlusions and other ocular problems that may challenge clinicians. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27079282", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 469, "text": "Etiologies are various but symptomatic hyperviscosity is more common in Waldenstr\u00f6m's macroglobulinemia and multiple myeloma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25778852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Double filtration plasmapheresis in a dog with multiple myeloma and hyperviscosity syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26623375", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "A 12 year old, 38 kg, mix-breed, intact male dog presented with a 20 day history of clinical signs consistent with hyperviscosity syndrome secondary to multiple myeloma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26623375", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 700, "text": "The present study reported for the first time the use of double filtration plasmapheresis to reduce clinical signs of hyperviscosity syndrome in a dog with multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26623375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "An otherwise healthy young man presents with bilateral CRVO as the first sign of hyperviscosity syndrome in the setting of new multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25383860", "endSection": "title" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1350, "text": " In haematology the most common indication for plasmapheresis is the supportive treatment of multiple myeloma. The procedure is performed in patients with high protein levels endangered with hyperviscosity syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26181153", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 421, "text": "Five to 10 percent of patients with multiple myeloma are suffered from the hyperviscosity syndrome because of increased serum viscosity due to the presence of myeloma protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7699907", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 744, "text": "Plasmapheresis is known as an efficient method for rapid improvement of the hyperviscosity syndrome, and double filtration plasmapheresis is most commonly used for plasma exchange of multiple myeloma patients in our country.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7699907", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1158, "text": "PE is the most effective method in the treatment of hyperviscosity syndrome often seen with multiple myeloma and Waldenstr\u00f6m's macroglobulinemia, and it is therapy of choice for this complication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9046114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Patients with multiple myeloma who have complications secondary to hyperviscosity are treated by chemotherapy and/or plasmapheresis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6155195", "endSection": "abstract" } ] }, { "body": "What is the purpose of the FaceBase consortium?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24124010", "http://www.ncbi.nlm.nih.gov/pubmed/24303230", "http://www.ncbi.nlm.nih.gov/pubmed/27287806", "http://www.ncbi.nlm.nih.gov/pubmed/26168040", "http://www.ncbi.nlm.nih.gov/pubmed/28261023", "http://www.ncbi.nlm.nih.gov/pubmed/21458441" ], "ideal_answer": [ "The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health, is designed to accelerate understanding of craniofacial developmental biology by generating comprehensive data resources to empower the research community, exploring high-throughput technology, fostering new scientific collaborations among researchers and human/computer interactions, facilitating hypothesis-driven research and translating science into improved health care to benefit patients.", "The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health, is designed to accelerate understanding of craniofacial developmental biology by generating comprehensive data resources to empower the research community, exploring high-throughput technology, fostering new scientific collaborations among researchers and human/computer interactions, facilitating hypothesis-driven research and translating science into improved health care to benefit patients. " ], "type": "summary", "id": "5a6d1db1b750ff4455000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The FaceBase Consortium: a comprehensive resource for craniofacial researchers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27287806", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 521, "text": "The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health, is designed to accelerate understanding of craniofacial developmental biology by generating comprehensive data resources to empower the research community, exploring high-throughput technology, fostering new scientific collaborations among researchers and human/computer interactions, facilitating hypothesis-driven research and translating science into improved health care to benefit patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27287806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "The FaceBase Consortium consists of ten interlinked research and technology projects whose goal is to generate craniofacial research data and technology for use by the research community through a central data management and integrated bioinformatics hub.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The FaceBase Consortium: a comprehensive program to facilitate craniofacial research.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458441", "endSection": "title" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1291, "text": "The FaceBase website (http://www.facebase.org) will serve as a web home for these efforts, providing interactive tools for exploring these datasets, together with discussion forums and other services to support and foster collaboration within the craniofacial research community.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458441", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 924, "text": "The resources generated by the FaceBase projects include a number of dynamic imaging modalities, genome-wide association studies, software tools for analyzing human facial abnormalities, detailed phenotyping, anatomical and molecular atlases, global and specific gene expression patterns, and transcriptional profiling over the course of embryonic and postnatal development in animal models and humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27287806", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1295, "text": "The FaceBase website (http://www.facebase.org) will serve as a web home for these efforts, providing interactive tools for exploring these datasets, together with discussion forums and other services to support and foster collaboration within the craniofacial research community.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The NIH FACEBASE consortium was established in part to create a central resource for craniofacial researchers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26168040", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1336, "text": "This FACEBASE resource is designed to promote discovery by the craniofacial research community.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26168040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "We introduce the Ontology of Craniofacial Development and Malformation (OCDM), a project of the NIH-funded FaceBase consortium, whose goal is to gather data from multiple species, at levels ranging from genes to gross anatomy, in order to understand the causes of craniofacial abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24303230", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1563, "text": "Our aim here is to create the Craniofacial Human Development Ontology (CHDO) to support the Ontology of Craniofacial Development and Malformation (OCDM), which provides the infrastructure for integrating multiple and disparate craniofacial data generated by FaceBase researchers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28261023", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 597, "text": "The OCDM is a project of the NIDCR-sponsored FaceBase Consortium, whose goal is to promote and enable research into the genetic and epigenetic causes of specific craniofacial abnormalities through the provision of publicly accessible, integrated craniofacial data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24124010", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1567, "text": "Our aim here is to create the Craniofacial Human Development Ontology (CHDO) to support the Ontology of Craniofacial Development and Malformation (OCDM), which provides the infrastructure for integrating multiple and disparate craniofacial data generated by FaceBase researchers.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28261023", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "The FaceBase Consortium: a comprehensive resource for craniofacial researchers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27287806", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The FaceBase Consortium: a comprehensive program to facilitate craniofacial research.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21458441", "endSection": "title" } ] }, { "body": "What is TCGA2BED?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28049410" ], "ideal_answer": [ "Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. TCGA2BED is a software tool to search and retrieve TCGA (The Cancer Genome Atlas) data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase)." ], "type": "summary", "id": "5a75f2fc83b0d9ea66000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "TCGA2BED: extracting, extending, integrating, and querying The Cancer Genome Atlas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1131, "text": "Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types.RESULTS: We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase). We also provide and maintain an automatically updated data repository with publicly available Copy Number Variation, DNA-methylation, DNA-seq, miRNA-seq, and RNA-seq (V1,V2) experimental data of TCGA converted into the BED format, and their associated clinical and biospecimen meta data in attribute-value text format.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 559, "text": "We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 792, "text": "Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 597, "text": "In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types.
RESULTS: We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 830, "text": "Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 813, "text": "Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 580, "text": "We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 580, "text": "RESULTS We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "TCGA2BED: extracting, extending, integrating, and querying The Cancer Genome Atlas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049410", "endSection": "title" } ] }, { "body": "Does the human lncRNA LINC-PINT promote tumorigenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "http://www.ncbi.nlm.nih.gov/pubmed/29078818" ], "ideal_answer": [ "No. LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D062085" ], "type": "yesno", "id": "5a6e3fe3b750ff4455000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078818", "endSection": "title" }, { "offsetInBeginSection": 412, "offsetInEndSection": 966, "text": "Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078818", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 638, "text": "We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078818", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1170, "text": "These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 513, "text": "Our data demonstrate that Linc-pint expression is lower in plasma samples from PCa patients than from healthy individuals, and indicate that plasma Linc-pint levels are more sensitive than CA19-9 for detecting PCa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 942, "text": "Low plasma Linc-pint levels correlate with tumor recurrence, while low tumor Linc-pint levels correlate with poor prognosis for PCa patients after pancreatectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 676, "text": "We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078818", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 659, "text": "We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078818", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1174, "text": "These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078818", "endSection": "title" } ] }, { "body": "Is LDB1-mediated enhancer looping dependent on cohesin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28520978" ], "ideal_answer": [ "No. LDB1-mediated enhancer looping can be established independent of mediator and cohesin." ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0061774", "http://amigo.geneontology.org/amigo/term/GO:0061780", "http://amigo.geneontology.org/amigo/term/GO:0008278", "http://amigo.geneontology.org/amigo/term/GO:0001205", "http://amigo.geneontology.org/amigo/term/GO:0071921", "http://amigo.geneontology.org/amigo/term/GO:1905309", "http://amigo.geneontology.org/amigo/term/GO:0071923", "http://amigo.geneontology.org/amigo/term/GO:0071922", "http://amigo.geneontology.org/amigo/term/GO:1905339", "http://amigo.geneontology.org/amigo/term/GO:1905338", "http://amigo.geneontology.org/amigo/term/GO:0003705", "http://amigo.geneontology.org/amigo/term/GO:0071733", "https://meshb.nlm.nih.gov/record/ui?ui=D004742", "http://amigo.geneontology.org/amigo/term/GO:0001206" ], "type": "yesno", "id": "5a6e49a4b750ff445500004b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "LDB1-mediated enhancer looping can be established independent of mediator and cohesin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28520978", "endSection": "title" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1488, "text": "Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28520978", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1359, "text": "Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28520978", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1364, "text": "Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28520978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "LDB1-mediated enhancer looping can be established independent of mediator and cohesin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28520978", "endSection": "title" } ] }, { "body": "Describe nursemaid's elbow injury.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25035767", "http://www.ncbi.nlm.nih.gov/pubmed/7773660", "http://www.ncbi.nlm.nih.gov/pubmed/24553032", "http://www.ncbi.nlm.nih.gov/pubmed/17763294", "http://www.ncbi.nlm.nih.gov/pubmed/22706475", "http://www.ncbi.nlm.nih.gov/pubmed/25469607", "http://www.ncbi.nlm.nih.gov/pubmed/24276229", "http://www.ncbi.nlm.nih.gov/pubmed/12093966", "http://www.ncbi.nlm.nih.gov/pubmed/11153321", "http://www.ncbi.nlm.nih.gov/pubmed/21317693", "http://www.ncbi.nlm.nih.gov/pubmed/28503271", "http://www.ncbi.nlm.nih.gov/pubmed/4086775", "http://www.ncbi.nlm.nih.gov/pubmed/27836316", "http://www.ncbi.nlm.nih.gov/pubmed/7560033", "http://www.ncbi.nlm.nih.gov/pubmed/28753234" ], "ideal_answer": [ "Nursemaid's elbow is a radial head subluxation caused by axial traction on the extended arm while the forearm is pronated, allowing for slippage of the radial head. Nursemaid's elbow usually occurs in young children when longitudinal traction is placed on the arm." ], "type": "summary", "id": "5a67b152b750ff445500000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "BACKGROUND/AIM: Nursemaid's elbow usually occurs in young children when longitudinal traction is placed on the arm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27836316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Nursemaid's elbow is a radial head subluxation caused by axial traction on the extended arm while the forearm is pronated, allowing for slippage of the radial head.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503271", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 483, "text": "X-ray of the right elbow showed subluxation of the elbow joint with no obvious fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "BACKGROUND: Pulled elbow (nursemaid's elbow) is a common injury in young children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28753234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "INTRODUCTION: To provide an epidemiological description of radial head subluxation, also known as nursemaid's elbow, from a database of emergency department visits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25035767", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 282, "text": "In cases of pulled elbow also known as nursemaid's elbow or radial head subluxation, diagnosis is usually performed clinically. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25469607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "To provide an epidemiological description of radial head subluxation, also known as nursemaid's elbow, from a database of emergency department visits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25035767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Annular ligament displacement (ALD)--also termed radial head subluxation, nursemaid's elbow, or pulled elbow--can be successfully diagnosed and treated over the telephone by properly trained medical professionals instructing nonmedical caretakers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12093966", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 281, "text": "In cases of pulled elbow also known as nursemaid's elbow or radial head subluxation, diagnosis is usually performed clinically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25469607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Six instances of subluxation of the radial head (\"nursemaid's elbow, pulled elbow\") in babies in the first 6 months of life are presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4086775", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 190, "text": "A nursemaid's elbow most frequently occurs with transient longitudinal traction of the pronated forearm and extended elbow, which can be reduced by manipulation without sedation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22706475", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 115, "text": "Nursemaid's elbow usually occurs in young children when longitudinal traction is placed on the arm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27836316", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 495, "text": "Exceptions can be made in the case of nursemaid's elbow lesion (subluxation of the radial head; pronation douloureuse; Chassaignac lesion) with unambiguous mechanism of the trauma where no X-ray imaging is needed and in heavily dislocated fractures for which one plane can be sufficient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17763294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Recurrent nursemaid's elbow (annular ligament displacement) treatment via telephone.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12093966", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Nursemaid's elbow (subluxation of the radial head) is a common pediatric upper extremity injury encountered in the emergency and urgent care settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21317693", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 720, "text": "Nursemaid's elbow, also known as a pulled elbow or a subluxated radial head, may result from the specific activities described above and is the most common dislocation injury handled by pediatricians.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Subluxation of the radial head, or \"nursemaid's elbow,\" is a common injury among children aged 1 to 4 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7773660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Acute annular ligament interposition into the radiocapitellar joint (\"nursemaid's elbow\") is a common injury in children younger than 5 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7560033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "Nursemaid's elbow usually occurs in young children when longitudinal traction is placed on the arm. Several manipulative maneuvers have been described, although, the most effective treatment technique is yet unclear. The aim of this systematic review and meta-analysis was to compare the two most commonly performed maneuvers (supination-flexion and hyperpronation) in the treatment of nursemaid's elbow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27836316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Radial head subluxation, also known as 'pulled elbow', 'dislocated elbow' or 'nursemaid's elbow', is one of the most common upper extremity injuries in young children and a common reason to visit Emergency Department (ED).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24553032", "endSection": "abstract" } ] }, { "body": "What is trismus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27350892", "http://www.ncbi.nlm.nih.gov/pubmed/26058916", "http://www.ncbi.nlm.nih.gov/pubmed/25303582", "http://www.ncbi.nlm.nih.gov/pubmed/27627138", "http://www.ncbi.nlm.nih.gov/pubmed/26098612", "http://www.ncbi.nlm.nih.gov/pubmed/26768235" ], "ideal_answer": [ "Trimus is defined as restricted mouth opening due to disorder of the temporomandibular joint." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014313", "https://meshb.nlm.nih.gov/record/ui?ui=D013705" ], "type": "summary", "id": "5a7706b79e632bc066000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Trismus is characterized by a reduced ability to open the mouth, directly affecting many aspects of daily life, such as chewing, swallowing, speaking and maintaining oral hygiene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26058916", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 144, "text": "A mouth opening of 35 mm or less should be regarded as trismus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26098612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "BACKGROUND Trismus indicates severely restricted mouth opening of any aetiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26098612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Trismus is characterized by a reduced ability to open the mouth, directly affecting many aspects of daily life, such as chewing, swallowing, speaking and maintaining oral hygiene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26058916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Trismus is a restriction in the ability to open the mouth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25303582", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "BACKGROUND: Trismus, a restricted mouth opening in head and neck cancer patients may be caused by tumor infiltration in masticatory muscles, radiation-induced fibrosis or scarring after surgery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27627138", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 722, "text": "rismus, which is defined as the restricted mouth opening or jaw movement due to the disorder of temporo-mandibular joint (TMJ), is one of the possible late complications for radiotherapy of NPC ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27350892", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 143, "text": "In patients with oral cancer, trismus (maximum interincisal opening [MIO]<35\u00a0mm) can develop as a result of surgery and radiotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26768235", "endSection": "abstract" } ] }, { "body": "What is mechanism of action of Benralizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28583618", "http://www.ncbi.nlm.nih.gov/pubmed/28919200", "http://www.ncbi.nlm.nih.gov/pubmed/28737051", "http://www.ncbi.nlm.nih.gov/pubmed/28545978", "http://www.ncbi.nlm.nih.gov/pubmed/22136436", "http://www.ncbi.nlm.nih.gov/pubmed/25306557", "http://www.ncbi.nlm.nih.gov/pubmed/26205082", "http://www.ncbi.nlm.nih.gov/pubmed/28109128", "http://www.ncbi.nlm.nih.gov/pubmed/27119985", "http://www.ncbi.nlm.nih.gov/pubmed/29086236", "http://www.ncbi.nlm.nih.gov/pubmed/27859832", "http://www.ncbi.nlm.nih.gov/pubmed/29059618", "http://www.ncbi.nlm.nih.gov/pubmed/28406319", "http://www.ncbi.nlm.nih.gov/pubmed/27609406", "http://www.ncbi.nlm.nih.gov/pubmed/25208464", "http://www.ncbi.nlm.nih.gov/pubmed/28971769", "http://www.ncbi.nlm.nih.gov/pubmed/27906698", "http://www.ncbi.nlm.nih.gov/pubmed/27609408", "http://www.ncbi.nlm.nih.gov/pubmed/27097165", "http://www.ncbi.nlm.nih.gov/pubmed/28530840" ], "ideal_answer": [ "Benralizumab is a humanised, anti-interleukin 5 receptor \u03b1 monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma." ], "type": "summary", "id": "5a722d9f2dc08e987e000004", "snippets": [ { "offsetInBeginSection": 131, "offsetInEndSection": 398, "text": "Since IL-5 plays an important role in the maturation, survival and migration of eosinophils, hence the pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5R\u03b1 have been developed and/or marketed, including Mepolizumab, Reslizumab, and Benralizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059618", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1248, "text": "Mepolizumab, reslizumab, and benralizumab target IL-5, a key cytokine for eosinophils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor \u03b1, immunoglobulin G (IgG)1\u03ba monoclonal antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28109128", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 688, "text": "A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27859832", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 892, "text": "These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2blockers (fevipiprant and timapiprant).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28583618", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 480, "text": "However, there is research underway investigating interleukin-based monoclonal antibodies such as benralizumab, an anti-IL-5R monoclonal antibody which is currently in phase III clinical development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28406319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "BACKGROUND: Benralizumab is a humanised, anti-interleukin 5 receptor \u03b1 monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28545978", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 448, "text": ". We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28530840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Benralizumab--a humanized mAb to IL-5R\u03b1 with enhanced antibody-dependent cell-mediated cytotoxicity--a novel approach for the treatment of asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136436", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Benralizumab is a monoclonal antibody that binds the \u03b1 subunit of the receptor to IL-5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136436", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 374, "text": "We assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor \u03b1 that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27609408", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 481, "text": "While previous monoclonal antibodies against the IL-5 ligand resulted in inconsistent improvements in asthma outcomes, benralizumab has shown promise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27119985", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 618, "text": "Benralizumab is a monoclonal antibody against IL-5 receptor, and has an enhanced antibody dependent cell-mediated cytotoxicity function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27119985", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 549, "text": "Anti-IL-5-based therapies (mepolizumab and reslizumab are humanized monoclonal antibodies (hmAbs) that recognize free IL-5, benralizumab is a hmAb directed at the \u03b1 subunit of the IL-5R) target the IL-5-signaling in eosinophilic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28737051", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 967, "text": "Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor \u03b1 monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28971769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Benralizumab is a humanized anti-IL5 receptor \u03b1 (IL5R\u03b1) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26205082", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor \u03b1 monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27609406", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Benralizumab is a monoclonal antibody that targets interleukin-5 receptor \u03b1 to deplete blood eosinophils and improve the clinical outcomes of allergic asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29086236", "endSection": "title" }, { "offsetInBeginSection": 750, "offsetInEndSection": 856, "text": "Expert opinion: Benralizumab has the advantage over other anti-IL-5 therapies to target the IL-5R\u03b1 itself.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28737051", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 328, "text": "Benralizumab is an anti-interleukin-5 receptor \u03b1 monoclonal antibody that depletes blood and airway eosinophils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27097165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Benralizumab is a monoclonal antibody that targets interleukin-5 receptor \u03b1 to deplete blood eosinophils and improve the clinical outcomes of allergic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29086236", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 536, "text": "Anti-IL-5-based therapies (mepolizumab and reslizumab are humanized monoclonal antibodies (hmAbs) that recognize free IL-5, benralizumab is a hmAb directed at the \u03b1 subunit of the IL-5R) target the IL-5-signaling in eosinophilic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28737051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "BACKGROUND Benralizumab is an anti-eosinophilic, anti-interleukin-5 receptor \u03b1 monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe, uncontrolled asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28919200", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 249, "text": "As IL-5 is implicated in disease states that are mediated by eosinophils, benralizumab is an attractive option for use in the management of asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "INTRODUCTION Benralizumab is a monoclonal antibody that binds the \u03b1 subunit of the receptor to IL-5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22136436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor \u03b1, immunoglobulin G (IgG) 1 \u03ba monoclonal antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28109128", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 447, "text": "We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28530840", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 342, "text": "In a phase 2b dose-ranging study, we aimed to assess the efficacy and safety of benralizumab, an anti-interleukin 5 receptor \u03b1 monoclonal antibody that depletes blood and airway eosinophils, in adults with uncontrolled eosinophilic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25306557", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 238, "text": "Benralizumab, an anti-interleukin-5 receptor \u03b1 monoclonal antibody, depletes blood and sputum eosinophils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25208464", "endSection": "abstract" } ] }, { "body": "Is there any link between ERCC1-XPF and cohesin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28368372" ], "ideal_answer": [ "Yes. ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes." ], "exact_answer": "yes", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0061774", "http://amigo.geneontology.org/amigo/term/GO:0008278", "http://amigo.geneontology.org/amigo/term/GO:0071921", "http://amigo.geneontology.org/amigo/term/GO:1905339", "http://amigo.geneontology.org/amigo/term/GO:0070522", "http://amigo.geneontology.org/amigo/term/GO:1905338", "http://www.disease-ontology.org/api/metadata/DOID:0110848", "http://amigo.geneontology.org/amigo/term/GO:0070312" ], "type": "yesno", "id": "5a6e4b72b750ff445500004c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "ERCC1-XPF cooperates with CTCF and cohesin to\u00a0facilitate the developmental silencing of imprinted\u00a0genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "title" }, { "offsetInBeginSection": 128, "offsetInEndSection": 1050, "text": "Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1 or exposure to MMC triggers the localization of CTCF to heterochromatin, the dissociation of the CTCF-cohesin complex and ATRX from promoters and ICRs, altered histone marks and\u00a0the aberrant developmental expression of imprinted genes without altering DNA methylation. We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 521, "text": "Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1050, "text": "We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 1051, "text": "We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1054, "text": "We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "ERCC1-XPF cooperates with CTCF and cohesin to\u00a0facilitate the developmental silencing of imprinted\u00a0genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "title" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1051, "text": "We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368372", "endSection": "abstract" } ] }, { "body": "Describe the Match BAM to VCF (MBV) method.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28186259" ], "ideal_answer": [ "MBV (Match BAM to VCF) is a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias." ], "type": "summary", "id": "5a6e4136b750ff4455000045", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "MBV: a method to solve sample mislabeling and detect technical bias in large combined genotype and sequencing assay datasets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "title" }, { "offsetInBeginSection": 196, "offsetInEndSection": 348, "text": "We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 769, "text": "Motivation: Large genomic datasets combining genotype and sequence data, such as for expression quantitative trait loci (eQTL) detection, require perfect matching between both data types.
Results: We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.
Availability and Implementation: MBV is implemented in C\u2009++\u2009as an independent component of the QTLtools software package, the binary and source codes are freely available at https://qtltools.github.io/qtltools/ .
Contact: olivier.delaneau@unige.ch or emmanouil.dermitzakis@unige.ch.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 349, "text": "Results We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 328, "text": "We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "MBV: a method to solve sample mislabeling and detect technical bias in large combined genotype and sequencing assay datasets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "title" } ] }, { "body": "Does Evolocumab improve cognitive function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28453187", "http://www.ncbi.nlm.nih.gov/pubmed/28207168", "http://www.ncbi.nlm.nih.gov/pubmed/28813214" ], "ideal_answer": [ "No, Evolocumab does not improve cognitive functioning." ], "exact_answer": "no", "type": "yesno", "id": "5a70ea8299e2c3af2600000b", "snippets": [ { "offsetInBeginSection": 2298, "offsetInEndSection": 2527, "text": "Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28813214", "endSection": "abstract" }, { "offsetInBeginSection": 1490, "offsetInEndSection": 2189, "text": "Results A total of 1204 patients were followed for a median of 19 months; the mean (\u00b1SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21\u00b12.62 in the evolocumab group and -0.29\u00b12.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28813214", "endSection": "abstract" }, { "offsetInBeginSection": 2298, "offsetInEndSection": 2526, "text": "Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28813214", "endSection": "abstract" }, { "offsetInBeginSection": 1844, "offsetInEndSection": 2188, "text": "There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28813214", "endSection": "abstract" } ] }, { "body": "Can radius fracture cause carpal tunnel syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10207976", "http://www.ncbi.nlm.nih.gov/pubmed/28336098", "http://www.ncbi.nlm.nih.gov/pubmed/23026468", "http://www.ncbi.nlm.nih.gov/pubmed/25920637", "http://www.ncbi.nlm.nih.gov/pubmed/28511570", "http://www.ncbi.nlm.nih.gov/pubmed/28638948", "http://www.ncbi.nlm.nih.gov/pubmed/27454517", "http://www.ncbi.nlm.nih.gov/pubmed/26566562", "http://www.ncbi.nlm.nih.gov/pubmed/21786553", "http://www.ncbi.nlm.nih.gov/pubmed/21505639", "http://www.ncbi.nlm.nih.gov/pubmed/29169594" ], "ideal_answer": [ "Yes, carpal tunnel syndrome is a common complication associated with distal radius fractures." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D002349", "http://www.disease-ontology.org/api/metadata/DOID:12169" ], "type": "yesno", "id": "5a72284b2dc08e987e000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Carpal tunnel syndrome (CTS) after distal radius fractures can present in 3 forms: acute, transient, and delayed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29169594", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 915, "text": "Complications were categorized as carpal tunnel syndrome, other sensibility issues, tendon complications including irritation and rupture, deep infections, complex regional pain syndrome and unidentified DRUJ or scapholunar problems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28336098", "endSection": "abstract" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1385, "text": "The overall complication rate was 14.6% (95% CI 11.8-17.7) including carpal tunnel syndrome or change in sensibility in 5.2% and tendon complications in 4.7%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28336098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "BACKGROUND: Although median nerve neuropathy and carpal tunnel syndrome (CTS) are known complications of both untreated and acutely treated distal radius fracture, median neuropathy after correction of distal radius malunion is not commonly reported in hand surgery literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28511570", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1040, "text": "Complications were defined as malunion, carpal tunnel syndrome, complex regional pain syndrome (CRPS), persistent pain, and subjective cosmetic deformity of the wrist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28638948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Carpal tunnel syndrome is a common complication associated with distal radius fractures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27454517", "endSection": "abstract" }, { "offsetInBeginSection": 1455, "offsetInEndSection": 1634, "text": "The patient also had minor complications of little finger flexor tendon irritation and carpal tunnel syndrome. She underwent implant removal and carpal tunnel release at 8 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25920637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Acute multiple flexor tendon injury and carpal tunnel syndrome after open distal radius fracture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26566562", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Carpal tunnel syndrome is a common condition and is a well-recognized phenomenon following a distal radius fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "We report the incidence of late onset post-operative carpal tunnel syndrome (late carpal tunnel syndrome) and late median nerve neuropathy after volar plating of distal radius fracture by conducting a retrospective study on volar plating for distal radius fracture performed during 2002 to 2006.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Carpal tunnel syndrome after distal radius fracture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026468", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "[Case-control study on transverse carpal ligament resection for the prevention of delayed carpal tunnel syndrome after distal radius fracture].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21786553", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Hand numbness and carpal tunnel syndrome after volar plating of distal radius fracture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505639", "endSection": "title" }, { "offsetInBeginSection": 465, "offsetInEndSection": 585, "text": "Delayed carpal tunnel syndrome presenting after a distal radius fracture has healed is best managed in standard fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026468", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 928, "text": "Being well known and accepted techniques of carpal tunnel release, we believe that the techniques described in this paper provide a viable alternative for carpal tunnel release in the setting of distal radius fracture fixation; with the added advantages of the original minimally invasive techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27454517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Carpal tunnel syndrome after fracture of the distal radius is a well known complication in adults, but in small children carpal tunnel syndrome is extremely rare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10207976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Carpal Tunnel Syndrome and Distal Radius Fractures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29169594", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Carpal tunnel syndrome after distal radius fracture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026468", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Hand numbness and carpal tunnel syndrome after volar plating of distal radius fracture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21505639", "endSection": "title" } ] }, { "body": "Can Logic Alignment Free (LAF) be used for bacterial genomes classification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26664519" ], "ideal_answer": [ "Yes. Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms can be used in order to assign biological samples to their taxa." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D008128", "https://meshb.nlm.nih.gov/record/ui?ui=D016680", "https://meshb.nlm.nih.gov/record/ui?ui=D002965" ], "type": "yesno", "id": "5a75f1f383b0d9ea66000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "LAF: Logic Alignment Free and its application to bacterial genomes classification.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26664519", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 1235, "text": "In this paper, we present Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms in order to assign biological samples to their taxa. This method searches for a minimal subset of k-mers whose relative frequencies are used to build classification models as disjunctive-normal-form logic formulas (if-then rules). We apply LAF successfully to the classification of bacterial genomes to their corresponding taxonomy. In particular, we succeed in obtaining reliable classification at different taxonomic levels by extracting a handful of rules, each one based on the frequency of just few k-mers. State of the art methods to adjust the frequency of k-mers to the character distribution of the underlying genomes have negligible impact on classification performance, suggesting that the signal of each class is strong and that LAF is effective in identifying it.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26664519", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 511, "text": "In this paper, we present Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms in order to assign biological samples to their taxa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26664519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "LAF: Logic Alignment Free and its application to bacterial genomes classification.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26664519", "endSection": "title" } ] }, { "body": "Is Marfan syndrome associated with chordal rupture?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17317544", "http://www.ncbi.nlm.nih.gov/pubmed/1888465", "http://www.ncbi.nlm.nih.gov/pubmed/14658812", "http://www.ncbi.nlm.nih.gov/pubmed/7790334", "http://www.ncbi.nlm.nih.gov/pubmed/1449438", "http://www.ncbi.nlm.nih.gov/pubmed/10441700", "http://www.ncbi.nlm.nih.gov/pubmed/18172522", "http://www.ncbi.nlm.nih.gov/pubmed/776440" ], "ideal_answer": [ "Yes, chordal rupture was described in patients with Marfan syndrome." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14323", "https://meshb.nlm.nih.gov/record/ui?ui=D008382" ], "type": "yesno", "id": "5a722a052dc08e987e000002", "snippets": [ { "offsetInBeginSection": 205, "offsetInEndSection": 481, "text": "Repair of the mitral valve in children who have Marfan syndrome is especially difficult due to the presence of generalized connective tissue disorder, which may lead to future elongation and rupture of chordae tendineae that were unaffected at the time of mitral valve repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18172522", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 640, "text": "Mitral regurgitation was caused by annulus dilatation in all patients, by leaflet prolapse in five patients, and by chordal rupture due to endocarditis in two. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14658812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Perioperative coronary artery spasm in modified Bentall's operation for annulo-aortic ectasia in Marfan's syndrome. A case report of perioperative chordal rupture of the mitral valve.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7790334", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 427, "text": "In a modified Bentall's operation (button technique), perioperative severe coronary artery spasm occurred in spite of the preventive use of nitroglycerin infusion, which resulted in profound ventricular fibrillation and subsequent chordal rupture of the mitral valve with Sellers IV regurgitation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7790334", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 952, "text": "It is worthy to report this case because of rarities such as Marfan's syndrome accompanied by Prinzmetal's variant angina, perioperative coronary artery spasm in modified Bentall's operation, and perioperative chordal rupture of the mitral valve and progression of mitral valve regurgitation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7790334", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1395, "text": " The four Major Complications- sudden death, infective endocarditis, spontaneous rupture of chordae tendineae, and progressive mitral regurgitation- are examined. Associated Cardiac Diseases, i.e., Marfan's syndrome, ostium secundum atrial septal defect and atherosclerotic coronary artery disease, are discussed, and a section on Treatment deals chiefly with prophylaxis for infective endocarditis and the management of arrhythmias and chest pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/776440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Acute mitral regurgitation due to chordal rupture in a patient with neonatal Marfan syndrome caused by a deletion in exon 29 of the FBN1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10441700", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Acute mitral regurgitation due to chordal rupture in a patient with neonatal Marfan syndrome caused by a deletion in exon 29 of the FBN1 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10441700", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Total chordal augmentation in a child with Marfan syndrome and severe mitral insufficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18172522", "endSection": "title" } ] }, { "body": "What is the mechanism of action of Fremanezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29171818", "http://www.ncbi.nlm.nih.gov/pubmed/28240610", "http://www.ncbi.nlm.nih.gov/pubmed/28972120", "http://www.ncbi.nlm.nih.gov/pubmed/28862758", "http://www.ncbi.nlm.nih.gov/pubmed/28642283", "http://www.ncbi.nlm.nih.gov/pubmed/29110503" ], "ideal_answer": [ "Fremanezumab is a monoclonal antibody directed against calcitonin-gene-related peptide (CGRP). It was shown to be effective for migraine preventive therapy. Other three monoclonal antibodies targeting the CGRP pathway are eptinezumab, erenumab and galcanezumab." ], "type": "summary", "id": "5a70e6e899e2c3af26000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 396, "text": "PURPOSE OF REVIEW: The results of phase 2 randomized controlled trials for the prevention of episodic and chronic migraine demonstrating the efficacy and safety of four mAbs targeting the calcitonin gene-related peptide (CGRP) pathway [ALD403 (eptinezumab), AMG334 (erenumab), LY2951742 (galcanezumab) and TEV48125 (fremanezumab)] have been published recently, and phase 3 trials are in process. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28240610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Selective Inhibition of Trigeminovascular Neurons by Fremanezumab: A Humanized Monoclonal Anti-CGRP Antibody.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28642283", "endSection": "title" }, { "offsetInBeginSection": 282, "offsetInEndSection": 570, "text": "Recently, a new class of such drugs, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs), were found to be effective in reducing the frequency of migraine. The purpose of this study was to better understand how the CGRP-mAb fremanezumab (TEV-48125) modulates meningeal sensory pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28642283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: Fremanezumab (formerly TEV-48125) is a monoclonal antibody directed against calcitonin-gene-related peptide (CGRP), a validated target for migraine preventive therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28862758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Fremanezumab-A Humanized Monoclonal Anti-CGRP Antibody-Inhibits Thinly Myelinated (A\u03b4) But Not Unmyelinated (C) Meningeal Nociceptors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972120", "endSection": "title" }, { "offsetInBeginSection": 220, "offsetInEndSection": 1128, "text": " As a new approach to migraine treatment, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs) were developed to reduce the availability of CGRP, and were found effective in reducing the frequency of chronic and episodic migraine. We recently tested the effect of fremanezumab (TEV-48125), a CGRP-mAb, on the activity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cranial dura, and found a selective inhibition of high-threshold but not wide-dynamic range class of neurons. To investigate the basis for this selective inhibitory effect, and further explore the mechanism of action of CGRP-mAbs, we tested the effect of fremanezumab on the cortical spreading depression-evoked activation of mechanosensitive primary afferent meningeal nociceptors that innervate the cranial dura, using single-unit recording in the trigeminal ganglion of anesthetized male rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972120", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 911, "text": "Discussion Clinical data from phase II and III trials of the four monoclonal antibodies targeting the CGRP pathway: Eptinezumab, erenumab, fremanezumab, and galcanezumab, collectively show a positive effect in the preventive treatment of episodic and chronic migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29110503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Background Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171818", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 741, "text": "We recently tested the effect of fremanezumab (TEV-48125), a CGRP-mAb, on the activity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cranial dura, and found a selective inhibition of high-threshold but not wide-dynamic range class of neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972120", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 1128, "text": "To investigate the basis for this selective inhibitory effect, and further explore the mechanism of action of CGRP-mAbs, we tested the effect of fremanezumab on the cortical spreading depression-evoked activation of mechanosensitive primary afferent meningeal nociceptors that innervate the cranial dura, using single-unit recording in the trigeminal ganglion of anesthetized male rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Background Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "BACKGROUND: Fremanezumab (formerly TEV-48125) is a monoclonal antibody directed against calcitonin-gene-related peptide (CGRP), a validated target for migraine preventive therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28862758", "endSection": "title" } ] }, { "body": "Is trastuzumab associated cardiotoxicity reversible?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27307412", "http://www.ncbi.nlm.nih.gov/pubmed/16258084", "http://www.ncbi.nlm.nih.gov/pubmed/26163096", "http://www.ncbi.nlm.nih.gov/pubmed/19147689", "http://www.ncbi.nlm.nih.gov/pubmed/23282614", "http://www.ncbi.nlm.nih.gov/pubmed/25964256", "http://www.ncbi.nlm.nih.gov/pubmed/18514938", "http://www.ncbi.nlm.nih.gov/pubmed/25772019", "http://www.ncbi.nlm.nih.gov/pubmed/24794210", "http://www.ncbi.nlm.nih.gov/pubmed/21310845", "http://www.ncbi.nlm.nih.gov/pubmed/15177418", "http://www.ncbi.nlm.nih.gov/pubmed/19669637", "http://www.ncbi.nlm.nih.gov/pubmed/23414468", "http://www.ncbi.nlm.nih.gov/pubmed/26992012", "http://www.ncbi.nlm.nih.gov/pubmed/24905295", "http://www.ncbi.nlm.nih.gov/pubmed/18484781", "http://www.ncbi.nlm.nih.gov/pubmed/26836985", "http://www.ncbi.nlm.nih.gov/pubmed/28694974", "http://www.ncbi.nlm.nih.gov/pubmed/28977908" ], "ideal_answer": [ "Cardiotoxicity is a potential adverse effect of trastuzumab, manifesting as either an asymptomatic decline in left-ventricular ejection fraction or infrequently as largely reversible symptomatic heart failure (HF). Reduction of cardiac function by trastuzumab is mostly reversible, however, some patients, especially those with cardiac risk factors, may rarely experience chronic heart failure or prolonged left ventricular ejection fraction reduction." ], "concepts": [ "http://www.biosemantics.org/jochem#4002084", "https://meshb.nlm.nih.gov/record/ui?ui=D000068878", "https://meshb.nlm.nih.gov/record/ui?ui=D066126" ], "type": "summary", "id": "5a6f8dc6b750ff4455000058", "snippets": [ { "offsetInBeginSection": 254, "offsetInEndSection": 492, "text": "Although reduction of cardiac function by trastuzumab is mostly reversible, some patients, especially those with cardiac risk factors, may rarely experience chronic heart failure or prolonged left ventricular ejection fraction reduction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28694974", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 784, "text": "We report the rare case of a metastatic breast cancer in a woman without cardiac risk factors who experienced long-term irreversible cardiotoxicity after discontinuation of trastuzumab therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28694974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Long-term irreversible trastuzumab-induced cardiotoxicity for metastatic breast cancer in a patient without cardiac risk factors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28694974", "endSection": "title" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1562, "text": "Similar to prior observations in breast cancer, TIC in gastric cancer patients is not frequent or reversible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28977908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "BACKGROUND: Trastuzumab targets the human epidermal growth factor receptor-2 (HER2). Cardiotoxicity is a potential adverse effect, manifesting as either an asymptomatic decline in left-ventricular ejection fraction or infrequently as largely reversible symptomatic heart failure (HF). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27307412", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 1156, "text": "Furthermore, recent retrospective studies have shown an increased incidence of heart failure and/or cardiomyopathy in patients treated with trastuzumab, that can persist many years after the conclusion of the therapy, thus suggesting that the side toxic effects are not always reversible as it was initially proposed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26836985", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 230, "text": "Trastuzumab-induced CT may be reversible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26992012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "BACKGROUND: Trastuzumab, a HER2 monoclonal antibody, has transformed the prognosis of patients with the aggressive HER2-positive breast cancer type. Trastuzumab augments the cardiotoxic effects of anthracyclines, but its effect is thought to be at least partially reversible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25772019", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1711, "text": "CONCLUSIONS: LV dilation and subclinical impairment in cardiac function persists>2\u00a0years after the end of anthracycline and trastuzumab treatment, without significant recovery after trastuzumab cessation, suggestive of long-term underlying cardiac damage and remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25772019", "endSection": "abstract" }, { "offsetInBeginSection": 1874, "offsetInEndSection": 2037, "text": "Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed, particularly in vulnerable populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25964256", "endSection": "abstract" }, { "offsetInBeginSection": 1399, "offsetInEndSection": 1519, "text": "CONCLUSION: PHARE confirm that the incidence of cardiac end-points remains low and mostly reversible after trastuzumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines can cause permanent damage, anti-HER2 agents may cause transitory and reversible cardiac dysfunction and others, such as those used in endocrine therapy, primarily disturb lipid metabolism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24794210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND: Although it is known that trastuzumab causes cardiotoxicity, its extent and reversibility are still in question.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905295", "endSection": "abstract" }, { "offsetInBeginSection": 1365, "offsetInEndSection": 1474, "text": "CONCLUSIONS: Decreased LVEF while undergoing trastuzumab therapy occurs frequently and is usually reversible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Trastuzumab-induced cardiotoxicity may induce reversible damage that is usually transitory and improves with trastuzumab withdrawal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23414468", "endSection": "abstract" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1791, "text": "The cardiotoxicity of trastuzumab also differs from traditional chemotherapy-induced cardiotoxicity in that it appears to be at least partially reversible, not related to the cumulative dose, and re-challenge is generally tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18484781", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 954, "text": "It is of note that the cardiotoxicity is generally reversible and can usually be managed with standard medical treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15177418", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 463, "text": "Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18514938", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 742, "text": "The cardiac dysfunction associated with trastuzumab is most often reversible upon discontinuation of treatment and initiation of standard medical therapy for CHF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19147689", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 562, "text": "Two categories of cardiotoxic side effects of antineoplastic drugs have been previously proposed: Type I cardiotoxicity, defined as permanent cardiotoxicity, is usually caused by anthracyclines; Type II cardiotoxicity, considered as reversible cardiotoxicity, has been mainly related to monoclonal antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26836985", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 487, "text": "The long-term significance of these events, isolating known cardiotoxic effects of anthracyclines from those of trastuzumab, and the appropriateness of referring to trastuzumab-related cardiotoxicity as reversible rather than responsive to trastuzumab withdrawal and heart failure medical therapy, are issues that continue to be debated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21310845", "endSection": "abstract" }, { "offsetInBeginSection": 1311, "offsetInEndSection": 1517, "text": "LVEF improved in most patients regardless of whether or not trastuzumab was continued.
CONCLUSIONS: Decreased LVEF while undergoing trastuzumab therapy occurs frequently and is usually reversible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Reversible cardiotoxicity in a 54-year-old woman treated with trastuzumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23282614", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258084", "endSection": "title" }, { "offsetInBeginSection": 570, "offsetInEndSection": 748, "text": "Type II cardiac changes occur in trastuzumab-treated patients, which do not appear to be dose-related, are not associated with histological changes, and are generally reversible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19669637", "endSection": "abstract" } ] }, { "body": "What is the role of nimotuzumab in treatment of pontine glioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23043252", "http://www.ncbi.nlm.nih.gov/pubmed/27379495", "http://www.ncbi.nlm.nih.gov/pubmed/24847085", "http://www.ncbi.nlm.nih.gov/pubmed/24638239", "http://www.ncbi.nlm.nih.gov/pubmed/25926743", "http://www.ncbi.nlm.nih.gov/pubmed/21784756", "http://www.ncbi.nlm.nih.gov/pubmed/23754473", "http://www.ncbi.nlm.nih.gov/pubmed/24696052", "http://www.ncbi.nlm.nih.gov/pubmed/21858608" ], "ideal_answer": [ "Nimotuzumab (an anti-EGFR monoclonal antibody) is being used for treatment of pontine gliomas. Nimotuzumab is a very well-tolerated drug with acceptable toxicity, and it may have promising value in the combination treatment. Clinical trials evaluating efficacy of nimotuzumab are ongoing." ], "type": "summary", "id": "5a7610ca83b0d9ea6600001b", "snippets": [ { "offsetInBeginSection": 860, "offsetInEndSection": 1011, "text": "Targeted therapy protocols included radiation therapy along with treatment by erlotinib, cilengitide, or an association of nimotuzumab and vinblastine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27379495", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 917, "text": ". We found that nimotuzumab with or without radiotherapy, chemotherapy in newly diagnosed or recurrent HGG, such as glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), and diffuse intrinsic pontine glioma (DIPG), might improve the response rate or the survival time. In conclusion, nimotuzumab is a very well-tolerated drug with acceptable toxicity, and it may have promising value in the combination treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25926743", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1680, "text": "Time to progression following initiation of nimotuzumab for the 4 patients with SD or better at W18 was 119, 157, 182 and 335 days, respectively. Median survival time was 3.2 months. Two patients lived 663 and 481 days from the start of nimotuzumab.CONCLUSIONS: Modest activity of nimotuzumab in DIPG, which has been shown previously, was confirmed: A small subset of DIPG patients appeared to benefit from anti-EGFR antibody treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24847085", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1096, "text": "Additionally, 1\u00a0patient received nimotuzumab once per week. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24638239", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 229, "text": "Findings on the role of EGFR signaling in the onset of childhood DIPG prompted the use of nimotuzumab, an anti-EGFR monoclonal antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696052", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1349, "text": " The nimotuzumab/vinorelbine combination was very well tolerated, with no acute side-effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696052", "endSection": "abstract" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1641, "text": "This strategy generated interesting results and warrants further investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696052", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 269, "text": "Combining craniospinal irradiation (CSI) with concurrent temozolomide and nimotuzumab therapy may slightly improve tumor control and overall survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754473", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 591, "text": "Here, we describe the case of an 8-year-old girl with primary metastatic DIPG who received craniospinal radiotherapy, a local boost, and concurrent temozolomide and nimotuzumab treatment based on an individual therapy recommendation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754473", "endSection": "abstract" }, { "offsetInBeginSection": 744, "offsetInEndSection": 872, "text": "The most frequently used drugs were etoposide (14), bevacizumab (13), irinotecan (13), nimotuzumab (13), and valproic acid (13).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21858608", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1104, "text": "Recent studies of nimotuzumab indicate the reason for the lack of toxicity, which is the most attractive argument for its clinical use besides modest efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23043252", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1263, "text": ". Studies are also ongoing in pediatric HGG with 2 EGFR inhibitors: cetuximab and nimotuzumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21784756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Craniospinal irradiation with concurrent temozolomide and nimotuzumab in a child with primary metastatic diffuse intrinsic pontine glioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754473", "endSection": "title" }, { "offsetInBeginSection": 773, "offsetInEndSection": 917, "text": "In conclusion, nimotuzumab is a very well-tolerated drug with acceptable toxicity, and it may have promising value in the combination treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25926743", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 772, "text": "We found that nimotuzumab with or without radiotherapy, chemotherapy in newly diagnosed or recurrent HGG, such as glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), and diffuse intrinsic pontine glioma (DIPG), might improve the response rate or the survival time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25926743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Craniospinal irradiation with concurrent temozolomide and nimotuzumab in a child with primary metastatic diffuse intrinsic pontine glioma. A compassionate use treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754473", "endSection": "title" } ] }, { "body": "Describe annotatr", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28369316" ], "ideal_answer": [ "Analysis of next-generation sequencing data often results in a list of genomic regions. These may include differentially methylated CpGs/regions, transcription factor binding sites, interacting chromatin regions, or GWAS-associated SNPs, among others. A common analysis step is to annotate such genomic regions to genomic annotations (promoters, exons, enhancers, etc.). The annotatr Bioconductor package flexibly and quickly summarizes and plots annotations of genomic regions. The annotatr package reports all intersections of regions and annotations, giving a better understanding of the genomic context of the regions." ], "type": "summary", "id": "5a6e33e4b750ff4455000041", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 1343, "text": "Analysis of next-generation sequencing data often results in a list of genomic regions. These may include differentially methylated CpGs/regions, transcription factor binding sites, interacting chromatin regions, or GWAS-associated SNPs, among others. A common analysis step is to annotate such genomic regions to genomic annotations (promoters, exons, enhancers, etc.). Existing tools are limited by a lack of annotation sources and flexible options, the time it takes to annotate regions, an artificial one-to-one region-to-annotation mapping, a lack of visualization options to easily summarize data, or some combination thereof.Results: We developed the annotatr Bioconductor package to flexibly and quickly summarize and plot annotations of genomic regions. The annotatr package reports all intersections of regions and annotations, giving a better understanding of the genomic context of the regions. A variety of graphics functions are implemented to easily plot numerical or categorical data associated with the regions across the annotations, and across annotation intersections, providing insight into how characteristics of the regions differ across the annotations. We demonstrate that annotatr is up to 27\u00d7 faster than comparable R packages. Overall, annotatr enables a richer biological interpretation of experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 1285, "offsetInEndSection": 1631, "text": "Overall, annotatr enables a richer biological interpretation of experiments.
Availability and Implementation: http://bioconductor.org/packages/annotatr/ and https://github.com/rcavalcante/annotatr.
Contact: rcavalca@umich.edu.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 936, "text": "The annotatr package reports all intersections of regions and annotations, giving a better understanding of the genomic context of the regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 792, "text": "Existing tools are limited by a lack of annotation sources and flexible options, the time it takes to annotate regions, an artificial one-to-one region-to-annotation mapping, a lack of visualization options to easily summarize data, or some combination thereof.
Results: We developed the annotatr Bioconductor package to flexibly and quickly summarize and plot annotations of genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 919, "text": "The annotatr package reports all intersections of regions and annotations, giving a better understanding of the genomic context of the regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 775, "text": "Results We developed the annotatr Bioconductor package to flexibly and quickly summarize and plot annotations of genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1345, "text": "Overall, annotatr enables a richer biological interpretation of experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 754, "text": "We developed the annotatr Bioconductor package to flexibly and quickly summarize and plot annotations of genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 898, "text": "The annotatr package reports all intersections of regions and annotations, giving a better understanding of the genomic context of the regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28369316", "endSection": "abstract" } ] }, { "body": "What is Blount's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24479742", "http://www.ncbi.nlm.nih.gov/pubmed/27741108", "http://www.ncbi.nlm.nih.gov/pubmed/3301898", "http://www.ncbi.nlm.nih.gov/pubmed/15481748", "http://www.ncbi.nlm.nih.gov/pubmed/25932193", "http://www.ncbi.nlm.nih.gov/pubmed/23610758", "http://www.ncbi.nlm.nih.gov/pubmed/880738", "http://www.ncbi.nlm.nih.gov/pubmed/8657465", "http://www.ncbi.nlm.nih.gov/pubmed/20698458", "http://www.ncbi.nlm.nih.gov/pubmed/23833842", "http://www.ncbi.nlm.nih.gov/pubmed/20609637", "http://www.ncbi.nlm.nih.gov/pubmed/27276637", "http://www.ncbi.nlm.nih.gov/pubmed/27583129", "http://www.ncbi.nlm.nih.gov/pubmed/20234769", "http://www.ncbi.nlm.nih.gov/pubmed/19370370", "http://www.ncbi.nlm.nih.gov/pubmed/18401672", "http://www.ncbi.nlm.nih.gov/pubmed/19794178" ], "ideal_answer": [ "Blount's disease (tibia vara) is a progressive form of genu varum due to asymmetrical inhibition of the postero medial portion of the proximal tibial epiphysis. It causes causes genu varum and internal tibial torsion. It is the most common cause of pathologic genu varum in children and adolescents" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14798" ], "type": "summary", "id": "5a75eb6483b0d9ea66000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Guided growth for tibia vara (Blount's disease).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27741108", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Blount's disease is commonly attributed to an intrinsic, idiopathic defect in the posteromedial proximal tibial physis resulting in progressive bowing of the leg, intoeing, and lateral knee thrust.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27741108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Blount's disease is an uncommon disorder of postero-medial proximal tibial physis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25932193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Blount's disease is a progressive form of genu varum due to asymmetrical inhibition of the postero medial portion of the proximal tibial epiphysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27583129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Infantile Blount's disease is a condition that causes genu varum and internal tibial torsion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23610758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Blount's disease, or tibia vara, is the most common cause of pathologic genu varum in children and adolescents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24479742", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 398, "text": "In an attempt to improve the post-operative outcomes and reduce known neurologic complications, we used discrete multimodality recording and stimulation models to identify areas of motor and sensory function in eighteen (18) pediatric patients presenting with Tibia Vara (Blount's Disease). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23833842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Late-onset tibia vara or Blount's disease is the most common cause of pathologic genu varum in children and adolescents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20698458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "PURPOSE: Oblique proximal tibial osteotomy is a useful option for correcting deformity associated with Blount's disease (tibia vara).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20234769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "INTRODUCTION: In stage\u00a01 of all currently accepted classifications for infantile tibia vara, the diagnosis is difficult between physiological bowing and true Blount's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20609637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND: Blount's disease is a multi-planar deformity affecting the pediatric population which leads to varus alignment of the lower extremities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19370370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "In 1937 Blount described a series of 28 patients with 'Tibia vara'. Since then, a number of deformities in the tibia and the femur have been described in association with this condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19794178", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 459, "text": "A LSG was done in a 10-year-old boy, body mass index (BMI) 42, who has Blount's disease (tibia vara) with severe pain at the knee joints that made him a wheelchair-bound person. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18401672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "A review of the English literature on Blount disease (osteochondrosis deformans tibiae; tibia vara) revealed that two forms of the disease, infantile and adolescent, are recognized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3301898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND: Blount's disease is a multi-planar deformity affecting the pediatric population which leads to varus alignment of the lower extremities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19370370", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 79, "text": "Blount disease can be defined as idiopathic proximal tibial vara.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27276637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BACKGROUND Blount's disease is a multi-planar deformity affecting the pediatric population which leads to varus alignment of the lower extremities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19370370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Blount's disease or congenital tibia vara is a clinical entity characterized by tibia bowing, tibia torsion, and beaking of the medial tibia metaphysis on plain radiograph.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15481748", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 902, "text": "In view of the spontaneous recovery of all investigated patients, it must be doubted whether a diagnosis of infantile tibia vara can be made in early infancy, and whether infantile Blount's disease is a diagnosis in its own right.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8657465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Blount's disease is a progressive form of genu varum due to asymmetrical inhibition of the postero medial portion of the proximal tibial epiphysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27583129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "INTRODUCTION In stage\u00a01 of all currently accepted classifications for infantile tibia vara, the diagnosis is difficult between physiological bowing and true Blount's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20609637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "A family is described with infantile Blount's disease (tibia vara) following an autosomal dominant mode of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/880738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Biochemical observations in Blount's disease (infantile tibia vara).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15481748", "endSection": "title" } ] }, { "body": "Describe mechanism of action of Nusinersen.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28244991", "http://www.ncbi.nlm.nih.gov/pubmed/28229309", "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "http://www.ncbi.nlm.nih.gov/pubmed/29091570", "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "http://www.ncbi.nlm.nih.gov/pubmed/28400976", "http://www.ncbi.nlm.nih.gov/pubmed/29067661", "http://www.ncbi.nlm.nih.gov/pubmed/28485722" ], "ideal_answer": [ "Nusinersen is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene. This modulates the splicing of the SMN2 mRNA transcript to include exon 7, thereby increasing the production of full-length SMN protein. It is approved for treatment of spinal muscular atrophy." ], "type": "summary", "id": "5a70e88699e2c3af2600000a", "snippets": [ { "offsetInBeginSection": 183, "offsetInEndSection": 449, "text": "In 2016, the US Food and Drug Administration (FDA)-approved Exondys 51 (eteplirsen) and Spinraza (nusinersen), the first exon skipping and exon inclusion drugs, to treat patients with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29067661", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 804, "text": "Notably, the first new central nervous system (CNS)-targeted oligonucleotide-based drug (nusinersen/Spinraza) was approved by US Food and Drug Administration (FDA) in late 2016 and several other compounds are in advanced clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28244991", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 717, "text": "Nusinersen (SPINRAZA\u2122) is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene. This modulates the splicing of the SMN2 mRNA transcript to include exon 7, thereby increasing the production of full-length SMN protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28229309", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 695, "text": "Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1) discovered in 2004 at the University of Massachusetts Medical School. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28485722", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1125, "text": "Spinraza\u2122showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza\u2122is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28400976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMNRx), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 643, "text": "Nusinersen is specifically designed to alter splicing of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron (SMN) protein that is deficient in patients with spinal muscular atrophy.
METHODS: This open-label, phase 2, escalating dose clinical study assessed the safety and tolerability, pharmacokinetics, and clinical efficacy of multiple intrathecal doses of nusinersen (6 mg and 12 mg dose equivalents) in patients with infantile-onset spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27939059", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 510, "text": "Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein.
METHODS: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29091570", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 694, "text": "Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1) discovered in 2004 at the University of Massachusetts Medical School.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28485722", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 580, "text": "Nusinersen (SPINRAZA\u2122) is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28229309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "OBJECTIVE To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMNRx), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865511", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 529, "text": "With the recent US Food and Drug Administration approval of nusinersen (Spinraza), the potential for correction of SMN2 exon 7 splicing as an SMA therapy has been affirmed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28485722", "endSection": "abstract" } ] }, { "body": "Describe King\u2013Kopetzky syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14570238", "http://www.ncbi.nlm.nih.gov/pubmed/10997453", "http://www.ncbi.nlm.nih.gov/pubmed/8738633", "http://www.ncbi.nlm.nih.gov/pubmed/20380613", "http://www.ncbi.nlm.nih.gov/pubmed/20500033", "http://www.ncbi.nlm.nih.gov/pubmed/14558893", "http://www.ncbi.nlm.nih.gov/pubmed/10380733", "http://www.ncbi.nlm.nih.gov/pubmed/11603771", "http://www.ncbi.nlm.nih.gov/pubmed/16562562", "http://www.ncbi.nlm.nih.gov/pubmed/8985564" ], "ideal_answer": [ "The principal symptom of subjects suffering from King-Kopetzky syndrome (Obscure Auditory Dysfunction) is perceived difficulty in recognizing and understanding speech in noisy backgrounds. For some patients, minor disturbances in auditory function, e.g. a deteriorated signal-to-noise ratio for speech, can be demonstrated; for others, all measurements of hearing are normal." ], "type": "summary", "id": "5a7602be83b0d9ea6600000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "At least 10% of people who present for help with hearing difficulties will be found to have normal hearing thresholds. These cases are clinically categorized as King-Kopetzky syndrome (KKS), obscure auditory dysfunction (OAD), or auditory processing disorder (APD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20380613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Illness perceptions and hearing difficulties in King-Kopetzky syndrome: what determines help seeking?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20500033", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "The present study explored illness perceptions of hearing difficulties amongst one hundred participants who reported experiencing hearing difficulties despite normal audiometric thresholds. This experience is referred to as King-Kopetzky syndrome (KKS), obscure auditory dysfunction (OAD), or auditory processing disorder (APD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20500033", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1155, "text": "Decreases in DPOAE level appear to represent evidence of minor cochlear pathology, and provide a pathological basis for the difficulty of hearing speech in the presence of background noise, which characterizes King-Kopetzky syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16562562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "The principal symptom of subjects suffering from King-Kopetzky syndrome is a perceived difficulty in recognizing and understanding speech in noisy backgrounds. For some patients, minor disturbances in auditory function, e.g. a deteriorated signal-to-noise ratio for speech, can be demonstrated; for others, all measurements of hearing are normal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "King Kopetzky Syndrome (KKS) is a common condition in which individuals with normal audiograms complain of hearing difficulties, particularly in noisy places.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11603771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "King-Kopetzky syndrome (Obscure Auditory Dysfunction, OAD) has been recognized as a clinically distinct condition in audiological and ENT clinics. It is characterized by normal hearing thresholds on pure tone audiometry (PTA) but complaints of difficulties in understanding speech in the presence of background noise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10997453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "King-Kopetzky syndrome is characterized by auditory disability with a clinically normal hearing threshold. The main reported disability is hearing speech in the presence of background noise. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8738633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Hearing complaints of patients with King-Kopetzky syndrome (obscure auditory dysfunction).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985564", "endSection": "title" }, { "offsetInBeginSection": 132, "offsetInEndSection": 386, "text": "The main findings are that complaints were commonly focused on the categories of 'live speech' and 'electronic speech' difficulties in patients with King-Kopetzky syndrome, particularly the auditory difficulties of speech in noise and group conversation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "The condition in which individuals with normal pure tone audiograms complain of hearing difficulties, especially in the presence of background noise, (normal pure tone audiograms), has had a number of different names. The present term King-Kopetzky Syndrome was coined by Hinchcliffe in 1992.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14558893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The principal symptom of subjects suffering from King-Kopetzky syndrome is a perceived difficulty in recognizing and understanding speech in noisy backgrounds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570238", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1159, "text": "Decreases in DPOAE level appear to represent evidence of minor cochlear pathology, and provide a pathological basis for the difficulty of hearing speech in the presence of background noise, which characterizes King-Kopetzky syndrome.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16562562", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 386, "text": "The main findings are that complaints were commonly focused on the categories of 'live speech' and 'electronic speech' difficulties in patients with King-Kopetzky syndrome, particularly the auditory difficulties of speech in noise and group conversation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 621, "text": "The condition in which individuals with normal pure tone audiograms complain of hearing difficulties, especially in the presence of background noise, (normal pure tone audiograms), has had a number of different names. The present term King-Kopetzky Syndrome was coined by Hinchcliffe in 1992. This is a common condition reported in 5 - 10% of those attending clinics complaining of hearing problems. A dominant genetic aetiology has been found in a proportion of cases. It may be associated with minor peripheral or central auditory dysfunction, and frequently the individuals exhibit anxious or depressive personalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14558893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "The principal symptom of subjects suffering from King-Kopetzky syndrome is a perceived difficulty in recognizing and understanding speech in noisy backgrounds. For some patients, minor disturbances in auditory function, e.g. a deteriorated signal-to-noise ratio for speech, can be demonstrated; for others, all measurements of hearing are normal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570238", "endSection": "abstract" } ] }, { "body": "What is the 959 Nematode Genomes initiative?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22058131", "http://www.ncbi.nlm.nih.gov/pubmed/24058822" ], "ideal_answer": [ "The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/) has been launched. Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, it is anticipated that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla.", "The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D009348" ], "type": "summary", "id": "5a6e4592b750ff4455000047", "snippets": [ { "offsetInBeginSection": 370, "offsetInEndSection": 1622, "text": "The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058822", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1622, "text": "To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058822", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1194, "text": "To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24058822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "959 Nematode Genomes: a semantic wiki for coordinating sequencing projects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058131", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 339, "text": "In this article, we describe '959 Nematode Genomes'--a community-curated semantic wiki to coordinate the sequencing efforts of individual labs to collectively sequence 959 genomes spanning the phylum Nematoda.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "959 Nematode Genomes: a semantic wiki for coordinating sequencing projects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22058131", "endSection": "title" } ] }, { "body": "Which are the constitutive parts of a Genomic Regulatory Block (GRB)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17387144" ], "ideal_answer": [ "GRBs are spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes." ], "exact_answer": [ [ "highly conserved noncoding elements (HCNEs)" ], [ "developmental regulatory target genes" ], [ "phylogenetically and functionally unrelated \"bystander\" genes" ] ], "type": "list", "id": "5a6a2dcab750ff4455000023", "snippets": [ { "offsetInBeginSection": 114, "offsetInEndSection": 987, "text": "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 354, "text": "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "endSection": "abstract" } ] }, { "body": "Glecaprevir and Pibrentasvir are used for tratment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28929412", "http://www.ncbi.nlm.nih.gov/pubmed/28412293", "http://www.ncbi.nlm.nih.gov/pubmed/28807904", "http://www.ncbi.nlm.nih.gov/pubmed/28688001", "http://www.ncbi.nlm.nih.gov/pubmed/29020583", "http://www.ncbi.nlm.nih.gov/pubmed/28480743", "http://www.ncbi.nlm.nih.gov/pubmed/28951228", "http://www.ncbi.nlm.nih.gov/pubmed/28128852", "http://www.ncbi.nlm.nih.gov/pubmed/28800195" ], "ideal_answer": [ "The combination of direct-acting antivirals glecaprevir and pibrentasvir is effective for treatment of Hepatitis C virus infection." ], "exact_answer": [ "Hepatitis C virus infection" ], "type": "factoid", "id": "5a70e4b399e2c3af26000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28128852", "endSection": "title" }, { "offsetInBeginSection": 503, "offsetInEndSection": 736, "text": "This phase 2, open-label study (MAGELLAN-1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) \u00b1 ribavirin (RBV) in HCV genotype 1-infected patients with prior virologic failure to HCV DAA-containing therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28128852", "endSection": "abstract" }, { "offsetInBeginSection": 1584, "offsetInEndSection": 1802, "text": "CONCLUSION: The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA-containing therapy; RBV coadministration did not improve efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28128852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28412293", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 401, "text": "The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28412293", "endSection": "abstract" }, { "offsetInBeginSection": 1525, "offsetInEndSection": 1915, "text": "CONCLUSIONS: Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained virologic response rates in HCV genotypes 1-6-infected patients without cirrhosis following 8- or 12-week treatment durations.LAY SUMMARY: The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1-6 infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28412293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Glecaprevir and pibrentasvir are direct-acting antiviral agents being developed as combination therapy for the treatment of chronic hepatitis C virus infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28800195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "The combination of glecaprevir (formerly ABT-493), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (formerly ABT-530), an NS5A protein inhibitor, is being developed as treatment for HCV genotype 1 to 6 infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28807904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "BACKGROUND AND OBJECTIVE: Glecaprevir and pibrentasvir are pangenotypic direct-acting antiviral agents for the treatment of chronic hepatitis C virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28688001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Glecaprevir and pibrentasvir are direct-acting antiviral agents being developed as combination therapy for the treatment of chronic hepatitis C virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28800195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND AND OBJECTIVE: Glecaprevir and pibrentasvir are pangenotypic direct-acting antiviral agents for the treatment of chronic hepatitis C virus infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28688001", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "The combination of glecaprevir (formerly ABT-493), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (formerly ABT-530), an NS5A protein inhibitor, is being developed as treatment for HCV genotype 1 to 6 infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28807904", "endSection": "title" }, { "offsetInBeginSection": 801, "offsetInEndSection": 995, "text": "This article summarizes the milestones in the development of glecaprevir/pibrentasvir leading to its first global approval in the EU and subsequent approval in the USA for chronic HCV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929412", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 400, "text": "The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28412293", "endSection": "abstract" }, { "offsetInBeginSection": 1850, "offsetInEndSection": 2203, "text": "Four patients discontinued the trial treatment prematurely because of adverse events; three of these patients had a sustained virologic response.
CONCLUSIONS: Treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29020583", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 999, "text": "This article summarizes the milestones in the development of glecaprevir/pibrentasvir leading to its first global approval in the EU and subsequent approval in the USA for chronic HCV infection.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929412", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 755, "text": "We evaluated the safety and efficacy of 8 and 12 weeks' treatment with glecaprevir/pibrentasvir in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis in 3 separate phase 3 trials.
METHODS: We performed 2 open label, single-arm studies (SURVEYOR-II, Part 4 and ENDURANCE-4) and a randomized, double-blind, placebo-controlled study (ENDURANCE-2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28951228", "endSection": "abstract" }, { "offsetInBeginSection": 1746, "offsetInEndSection": 1967, "text": "Among patients receiving glecaprevir/pibrentasvir for 12 weeks, rates of SVR12 were 99.5% (95% CI, 98.5-100) in those infected with HCV genotype 2 and 99% (95% CI, 97.6-100) in those infected with HCV genotype 4, 5, or 6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28951228", "endSection": "abstract" }, { "offsetInBeginSection": 1939, "offsetInEndSection": 2123, "text": "Treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29020583", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 1066, "text": "Coadministration of glecaprevir 400\u00a0mg increased pibrentasvir 120 and 40\u00a0mg steady-state C and AUC values to 2.9-6.3-fold, and coadministration of glecaprevir 700\u00a0mg increased pibrentasvir 160\u00a0mg steady-state C and AUC values to up to sevenfold of the values when pibrentasvir was administered alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28688001", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 855, "text": "We conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease (with or without cirrhosis) with severe renal impairment, dependence on dialysis, or both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29020583", "endSection": "abstract" } ] }, { "body": "What is the drug target(s) for Belsomra?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27390287", "http://www.ncbi.nlm.nih.gov/pubmed/25227290", "http://www.ncbi.nlm.nih.gov/pubmed/28012090", "http://www.ncbi.nlm.nih.gov/pubmed/25336862", "http://www.ncbi.nlm.nih.gov/pubmed/28035034", "http://www.ncbi.nlm.nih.gov/pubmed/28365447", "http://www.ncbi.nlm.nih.gov/pubmed/28279667", "http://www.ncbi.nlm.nih.gov/pubmed/27825624", "http://www.ncbi.nlm.nih.gov/pubmed/26864332", "http://www.ncbi.nlm.nih.gov/pubmed/26416477", "http://www.ncbi.nlm.nih.gov/pubmed/27471419" ], "ideal_answer": [ "Belsomra is a dual orexin receptor antagonist for both the Ox1 and Ox2 receptors" ], "exact_answer": [ "orexin recptors" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000068797" ], "type": "factoid", "id": "5a777ab9faa1ab7d2e00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Suvorexant (Belsomra\u00ae) is a novel sedative hypnotic drug that is prescribed to promote sleep in patients with insomnia. It is the first of a new class of drugs classified as dual orexin receptor antagonists (DORAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27825624", "endSection": "abstract" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1754, "text": "dual orexin receptor antagonist suvorexant (Belsomra\u00ae) for the treatment of insomnia as a promising sign of the potential clinical utility of orexin-based therapies for the treatment of addiction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28012090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Suvorexant (Belsomra\u00ae) is a dual orexin receptor antagonist approved for the treatment of insomnia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28279667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Suvorexant is a dual orexin receptor agonist and is currently approved for the treatment of insomnia in the United States and Japan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28365447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Suvorexant (Belsomra(\u00ae)), a first-in-class, orally active dual orexin-1 receptor and orexin-2 receptor antagonist, has been developed by Merck for the treatment of insomnia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25227290", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1611, "text": "Last, we look ahead to the next decade of the research in this area, highlighting the recent FDA approval of the dual orexin receptor antagonist suvorexant (Belsomra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28012090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold-hopping approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27390287", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 801, "text": "Compound 80\u2009c [{(1S,6R)-3-(6,7-difluoroquinoxalin-2-yl)-3,8-diazabicyclo[4.2.0]octan-8-yl}(4-methyl-[1,1'-biphenyl]-2-yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27390287", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 489, "text": "Suvorexant is a dual orexin receptor antagonist (DORA) which is available for the treatment of insomnia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26416477", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 146, "text": "Suvorexant (MK-4305, Belsomra\u00ae) is a first-in-class dual orexin receptor antagonist approved in the USA and Japan for the treatment of insomnia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26864332", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 978, "text": "Suvorexant (Belsomra) is the first dual orexin receptor antagonist to be approved in the US and Japan and has demonstrated efficacy in decreasing time to sleep onset and increasing total sleep time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27471419", "endSection": "abstract" } ] }, { "body": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27375734", "http://www.ncbi.nlm.nih.gov/pubmed/28634592", "http://www.ncbi.nlm.nih.gov/pubmed/27088018", "http://www.ncbi.nlm.nih.gov/pubmed/28090050", "http://www.ncbi.nlm.nih.gov/pubmed/27928503", "http://www.ncbi.nlm.nih.gov/pubmed/29039237", "http://www.ncbi.nlm.nih.gov/pubmed/29099159", "http://www.ncbi.nlm.nih.gov/pubmed/27717592", "http://www.ncbi.nlm.nih.gov/pubmed/27471597", "http://www.ncbi.nlm.nih.gov/pubmed/26912914" ], "ideal_answer": [ "Yes, canagliflozin use can cause euglycemic diabetic ketoacidosis. In May 2015, the FDA issued a warning of ketoacidosis with use of sodium-glucose cotransporter-2 (SGLT-2) drug class." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000068896" ], "type": "yesno", "id": "5a6f922fb750ff4455000059", "snippets": [ { "offsetInBeginSection": 408, "offsetInEndSection": 1464, "text": "CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2\u00a0days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168\u00a0mg/dL. The urinalysis showed glucose>500\u00a0mg/dL and ketones of 80\u00a0mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93\u00a0mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36\u00a0h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27717592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28090050", "endSection": "title" }, { "offsetInBeginSection": 175, "offsetInEndSection": 442, "text": "We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28090050", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 930, "text": "Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29039237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27088018", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 479, "text": " However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27088018", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 380, "text": "At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27471597", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 664, "text": "We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26912914", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375734", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375734", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 596, "text": "Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634592", "endSection": "title" }, { "offsetInBeginSection": 822, "offsetInEndSection": 975, "text": "In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634592", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1233, "text": "SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634592", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 668, "text": "We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928503", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 668, "text": "We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928503", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 660, "text": "CONCLUSION Treatment with canagliflozin was associated with development of euglycemic ketoacidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29099159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28090050", "endSection": "title" }, { "offsetInBeginSection": 554, "offsetInEndSection": 665, "text": "We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634592", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375734", "endSection": "title" } ] }, { "body": "What is CellMaps?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27296979" ], "ideal_answer": [ "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them.", "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. CellMaps can easily be integrated in any web page by using an available JavaScript API. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. ", "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. CellMaps can easily be integrated in any web page by using an available JavaScript API. ", "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. CellMaps can easily be integrated in any web page by using an available JavaScript API.", "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. ", "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. CellMaps can easily be integrated in any web page by using an available JavaScript API. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services." ], "type": "summary", "id": "5a6e22b9b750ff445500003b", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 404, "text": "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. CellMaps can easily be integrated in any web page by using an available JavaScript API.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": ": CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "UNLABELLED: : CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "UNLABELLED: : CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296979", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "UNLABELLED : CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296979", "endSection": "abstract" } ] }, { "body": "Is there an association between Klinefelter syndrome and breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20698148", "http://www.ncbi.nlm.nih.gov/pubmed/20706705", "http://www.ncbi.nlm.nih.gov/pubmed/15119010", "http://www.ncbi.nlm.nih.gov/pubmed/21241366", "http://www.ncbi.nlm.nih.gov/pubmed/21246928", "http://www.ncbi.nlm.nih.gov/pubmed/25415740", "http://www.ncbi.nlm.nih.gov/pubmed/23464700", "http://www.ncbi.nlm.nih.gov/pubmed/9283592", "http://www.ncbi.nlm.nih.gov/pubmed/7125242", "http://www.ncbi.nlm.nih.gov/pubmed/16106025", "http://www.ncbi.nlm.nih.gov/pubmed/21204612", "http://www.ncbi.nlm.nih.gov/pubmed/3111653", "http://www.ncbi.nlm.nih.gov/pubmed/23909038", "http://www.ncbi.nlm.nih.gov/pubmed/15668471", "http://www.ncbi.nlm.nih.gov/pubmed/28675185", "http://www.ncbi.nlm.nih.gov/pubmed/24552677" ], "ideal_answer": [ "Yes, Klinefelter syndrome is associated with increased risk of male breast cancer. Other risk factors of male breast cancer are positive family history, and mutations in BRCA1 and specially BRCA2." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001244", "https://meshb.nlm.nih.gov/record/ui?ui=D007713", "https://meshb.nlm.nih.gov/record/ui?ui=D001943" ], "type": "yesno", "id": "5a68eabab750ff4455000015", "snippets": [ { "offsetInBeginSection": 1058, "offsetInEndSection": 1324, "text": "Screening for breast cancer in male-to-female transsexuals should be undertaken for those with additional risk factors (e.g., family history, BRCA2 mutation, Klinefelter syndrome) and should be available to those who desire screening, preferably in a clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25415740", "endSection": "abstract" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1289, "text": "Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24552677", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 529, "text": "Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23464700", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 185, "text": "The main risk factors include: the mutation of genes BRCA 1 and 2, Klinefelter's syndrome, alcohol, liver disease, obesity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23909038", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 368, "text": "Although aetiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and specially BRCA2) risk factors are already known. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21204612", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 800, "text": "The largest study found 19.2- and 57.8-fold increases in incidence and mortality, respectively, with particularly high risks among 47,XXY mosaics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21241366", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1408, "text": "CONCLUSIONS: Additional well-designed epidemiologic studies are needed to clarify which patients with KS are at a high risk of developing MBC and to distinguish between possible predisposing factors, including altered endogenous hormones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21241366", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 528, "text": "Major risk factors for developing male BC include clinical disorders involving hormonal imbalances (excess of estrogen or a deficiency of testosterone as seen in patients with Klinefelter syndrome) and a positive family history for breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20706705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20698148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Breast cancer in a patient with Klinefelter's syndrome is reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7125242", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 515, "text": "The increased conversion of testosterone to estradiol at the therapy with androgens might be responsible for the development of breast cancer in Klinefelter's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7125242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Patients with a 47,XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing cancer, especially male breast cancer and germ cell tumors, but rarely malignant hematologic disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9283592", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 327, "text": "The frequencies of diabetes mellitus, breast cancer, and germ cell neoplasia increases in Klinefelter's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15119010", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 457, "text": "There is evidence, however, to suggest that Klinefelter's males have an increased risk of breast cancer that approaches three percent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3111653", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 334, "text": "Klinefelter syndrome has been consistently associated with breast cancer in men (MBC).
CASE REPORT: We report a 54-year old man was diagnosed as synchronous bilateral breast cancer with Klinefelter syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1622, "text": "These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 735, "text": "Major genetic factors associated with an increased risk of breast cancer for men include BRCA2 mutations, which are believed to account for the majority of inherited breast cancer in men, Klinefelter syndrome, and a positive family history.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15668471", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 275, "text": "Those affected by Klinefelter's syndrome are at increased risk of systemic lupus erythematosus, breast cancer, non-Hodgkin's lymphoma, and lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28675185", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1624, "text": "CONCLUSIONS These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 1057, "text": "Compared with the general population, men with Klinefelter syndrome had higher mortality from lung cancer (SMR = 1.5, 95% CI = 1.0 to 2.0), breast cancer (SMR = 57.8, 95% CI = 18.8 to 135.0), and non-Hodgkin lymphoma (SMR = 3.5, 95% CI = 1.6 to 6.6) and lower mortality from prostate cancer (SMR = 0, 95% CI = 0 to 0.7).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 195, "text": "Klinefelter syndrome has been consistently associated with breast cancer in men (MBC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 528, "text": "Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23464700", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20698148", "endSection": "abstract" }, { "offsetInBeginSection": 1311, "offsetInEndSection": 1466, "text": "Klinefelter syndrome, in which patients carry XXY chromosome, may be present in men with breast cancer for this reason they often develop gynecomastia.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 187, "text": "Klinefelter syndrome has been consistently associated with breast cancer in men (MBC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21246928", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1580, "text": "These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16106025", "endSection": "abstract" } ] }, { "body": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028923", "http://www.ncbi.nlm.nih.gov/pubmed/27591080", "http://www.ncbi.nlm.nih.gov/pubmed/26630308", "http://www.ncbi.nlm.nih.gov/pubmed/26163694" ], "ideal_answer": [ "signeR: an empirical Bayesian approach to mutational signature discovery. Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques. The extraction of mutational signatures from high-throughput data still remains a daunting task.RESULTS: Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model.", "SomaticSignatures: inferring mutational signatures from single-nucleotide variants.Mutational signatures are patterns in the occurrence of somatic single-nucleotide variants that can reflect underlying mutational processes.The SomaticSignatures package provides flexible, interoperable and easy-to-use tools that identify such signatures in cancer sequencing data.It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows.AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project.Its documentation provides additional details on the methods and demonstrates applications to biological datasets.These mutagenic processes often produce characteristic mutational patterns called mutational signatures.The decomposition of a cancer genome's mutation catalog into mutations consistent with such signatures can provide valuable information about cancer etiology.Hence, one needs to be able to not only decompose a patient's mutational profile into signatures but also establish the accuracy of such decomposition.Results: We proposed two complementary ways of measuring confidence and stability of decomposition results and applied them to analyze mutational signatures in breast cancer genomes.", "signeR is an R package for a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model.", "signeR: an empirical Bayesian approach to mutational signature discovery. Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques.", "signeR: an empirical Bayesian approach to mutational signature discovery. The extraction of mutational signatures from high-throughput data still remains a daunting task.RESULTS: Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model. Results on real data agree well with current knowledge.AVAILABILITY AND IMPLEMENTATION: signeR is implemented in R and C\u2009++, and is available as a R package at http://bioconductor.org/packages/signeR", "signeR: an empirical Bayesian approach to mutational signature discovery.", "It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows.AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project. ", "Cancers arise as the result of somatically acquired changes in the DNA of cancer cells. However, in addition to the mutations that confer a growth advantage, cancer genomes accumulate a large number of somatic mutations resulting from normal DNA damage and repair processes as well as carcinogenic exposures or cancer related aberrations of DNA maintenance machinery. These mutagenic processes often produce characteristic mutational patterns called mutational signatures. The decomposition of a cancer genome's mutation catalog into mutations consistent with such signatures can provide valuable information about cancer etiology. SigneR, SignatureEstimation, pmsignature and SomaticSignatures are R packages that have been developed for the discovery of mutational signatures in cancer." ], "exact_answer": [ [ "signeR" ], [ "SignatureEstimation" ], [ "pmsignature" ], [ "SomaticSignatures" ] ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "https://meshb.nlm.nih.gov/record/ui?ui=D004252" ], "type": "list", "id": "5a7636d39e632bc066000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "signeR: an empirical Bayesian approach to mutational signature discovery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591080", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1809, "text": "Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques. Current methods based on optimization techniques are strongly sensitive to initial conditions due to high dimensionality and nonconvexity of the NMF paradigm. In this context, an important question consists in the determination of the actual number of signatures that best represent the data. The extraction of mutational signatures from high-throughput data still remains a daunting task.RESULTS: Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model. While requiring minimal intervention from the user, our method addresses the determination of the number of signatures directly as a model selection problem. In addition, we introduce two new concepts of significant clinical relevance for evaluating the mutational profile. The advantages brought by our approach are shown by the analysis of real and synthetic data. The later is used to compare our approach against two alternative methods mostly used in the literature and with the same NMF parametrization as the one considered here. Our approach is robust to initial conditions and more accurate than competing alternatives. It also estimates the correct number of signatures even when other methods fail. Results on real data agree well with current knowledge.AVAILABILITY AND IMPLEMENTATION: signeR is implemented in R and C\u2009++, and is available as a R package at http://bioconductor.org/packages/signeR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591080", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1606, "text": "Cancers arise as the result of somatically acquired changes in the DNA of cancer cells. However, in addition to the mutations that confer a growth advantage, cancer genomes accumulate a large number of somatic mutations resulting from normal DNA damage and repair processes as well as carcinogenic exposures or cancer related aberrations of DNA maintenance machinery. These mutagenic processes often produce characteristic mutational patterns called mutational signatures. The decomposition of a cancer genome's mutation catalog into mutations consistent with such signatures can provide valuable information about cancer etiology. However, the results from different decomposition methods are not always consistent. Hence, one needs to be able to not only decompose a patient's mutational profile into signatures but also establish the accuracy of such decomposition.Results: We proposed two complementary ways of measuring confidence and stability of decomposition results and applied them to analyze mutational signatures in breast cancer genomes. We identified both very stable and highly unstable signatures, as well as signatures that previously have not been associated with breast cancer. We also provided additional support for the novel signatures. Our results emphasize the importance of assessing the confidence and stability of inferred signature contributions.Availability: All tools developed in this paper have been implemented in an R package, called SignatureEstimation, which is available from https://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/index.cgi#signatureestimation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 2111, "text": "Recent advances in sequencing technologies have enabled the production of massive amounts of data on somatic mutations from cancer genomes. These data have led to the detection of characteristic patterns of somatic mutations or \"mutation signatures\" at an unprecedented resolution, with the potential for new insights into the causes and mechanisms of tumorigenesis. Here we present new methods for modelling, identifying and visualizing such mutation signatures. Our methods greatly simplify mutation signature models compared with existing approaches, reducing the number of parameters by orders of magnitude even while increasing the contextual factors (e.g. the number of flanking bases) that are accounted for. This improves both sensitivity and robustness of inferred signatures. We also provide a new intuitive way to visualize the signatures, analogous to the use of sequence logos to visualize transcription factor binding sites. We illustrate our new method on somatic mutation data from urothelial carcinoma of the upper urinary tract, and a larger dataset from 30 diverse cancer types. The results illustrate several important features of our methods, including the ability of our new visualization tool to clearly highlight the key features of each signature, the improved robustness of signature inferences from small sample sizes, and more detailed inference of signature characteristics such as strand biases and sequence context effects at the base two positions 5' to the mutated site. The overall framework of our work is based on probabilistic models that are closely connected with \"mixed-membership models\" which are widely used in population genetic admixture analysis, and in machine learning for document clustering. We argue that recognizing these relationships should help improve understanding of mutation signature extraction problems, and suggests ways to further improve the statistical methods. Our methods are implemented in an R package pmsignature (https://github.com/friend1ws/pmsignature) and a web application available at https://friend1ws.shinyapps.io/pmsignature_shiny/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26630308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "SomaticSignatures: inferring mutational signatures from single-nucleotide variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163694", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 761, "text": "Mutational signatures are patterns in the occurrence of somatic single-nucleotide variants that can reflect underlying mutational processes. The SomaticSignatures package provides flexible, interoperable and easy-to-use tools that identify such signatures in cancer sequencing data. It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows.AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project. Its documentation provides additional details on the methods and demonstrates applications to biological datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163694", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 294, "text": "The SomaticSignatures package provides flexible, interoperable and easy-to-use tools that identify such signatures in cancer sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "signeR: an empirical Bayesian approach to mutational signature discovery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591080", "endSection": "title" }, { "offsetInBeginSection": 756, "offsetInEndSection": 899, "text": "Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591080", "endSection": "abstract" }, { "offsetInBeginSection": 1628, "offsetInEndSection": 1965, "text": "Results on real data agree well with current knowledge.
AVAILABILITY AND IMPLEMENTATION: signeR is implemented in R and C\u2009++, and is available as a R package at http://bioconductor.org/packages/signeR CONTACT: itojal@cipe.accamargo.org.brSupplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591080", "endSection": "abstract" }, { "offsetInBeginSection": 1646, "offsetInEndSection": 1881, "text": "signeR is implemented in R and C\u2009++, and is available as a R package at http://bioconductor.org/packages/signeR CONTACT: itojal@cipe.accamargo.org.brSupplementary information: Supplementary data are available at Bioinformatics online..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591080", "endSection": "abstract" } ] }, { "body": "According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17137436", "http://www.ncbi.nlm.nih.gov/pubmed/16762931", "http://www.ncbi.nlm.nih.gov/pubmed/18497723", "http://www.ncbi.nlm.nih.gov/pubmed/17125447", "http://www.ncbi.nlm.nih.gov/pubmed/11276389", "http://www.ncbi.nlm.nih.gov/pubmed/12148078", "http://www.ncbi.nlm.nih.gov/pubmed/23145009", "http://www.ncbi.nlm.nih.gov/pubmed/23519746", "http://www.ncbi.nlm.nih.gov/pubmed/26871396", "http://www.ncbi.nlm.nih.gov/pubmed/12137304", "http://www.ncbi.nlm.nih.gov/pubmed/26543426", "http://www.ncbi.nlm.nih.gov/pubmed/19108808", "http://www.ncbi.nlm.nih.gov/pubmed/10682170", "http://www.ncbi.nlm.nih.gov/pubmed/28106792", "http://www.ncbi.nlm.nih.gov/pubmed/26280340", "http://www.ncbi.nlm.nih.gov/pubmed/15827427", "http://www.ncbi.nlm.nih.gov/pubmed/15940204", "http://www.ncbi.nlm.nih.gov/pubmed/10863169", "http://www.ncbi.nlm.nih.gov/pubmed/17469041" ], "ideal_answer": [ "Metabolic syndrome (MetS) is generally defined as a cluster of metabolically related cardiovascular risk factors which are often associated with the condition of insulin resistance, elevated blood pressure, and abdominal obesity.", "Metabolic syndrome (MetS) is generally defined as a cluster of metabolically related cardiovascular risk factors which are often associated with the condition of insulin resistance, elevated blood pressure, and abdominal obesity. " ], "exact_answer": [ [ "obesity" ], [ "hypertension" ], [ "dyslipdemia" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D024821", "https://meshb.nlm.nih.gov/record/ui?ui=D007333" ], "type": "list", "id": "5a981e66fcd1d6a10c00002f", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 156, "text": " Metabolic syndrome (MetS) is a collection of clinical conditions, including central obesity, hypertension, glucose intolerance and dyslipidemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26871396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Metabolic syndrome (MetS) is generally defined as a cluster of metabolically related cardiovascular risk factors which are often associated with the condition of insulin resistance, elevated blood pressure, and abdominal obesity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28106792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Metabolic syndrome, defined as a cluster of obesity, hypertension, dyslipidemia, and insulin resistance/glucose intolerance, has been identified as a major risk factor for coronary heart disease in women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15827427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Metabolic syndrome is a cluster of conditions that synergistically increase the risk of cardiovascular disease, type 2 diabetes, and premature mortality. The components are abdominal obesity, impaired glucose metabolism, dyslipidemia, and hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280340", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 633, "text": "MetS is recognized clinically by numerous constitutive traits, including abdominal obesity, hypertension, dyslipidemia (elevated triglycerides, low high-density lipoprotein cholesterol), and hyperglycemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26543426", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 521, "text": "Abdominal obesity is frequently associated with a collection of metabolic disorders that include elevated blood pressure, characteristic lipid abnormalities (low high-density lipoprotein cholesterol and high triglycerides) and increased fasting glucose, with an underlying situation of insulin resistance, which has been defined as metabolic syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23519746", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 698, "text": "The presence of 3 or more of the following 5 components (abdominal obesity, hypertriglyceridemia, low level of high density lipoprotein cholesterol, hypertension and high fasting blood glucose) allows to diagnose metabolic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15940204", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1182, "text": "The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19108808", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 728, "text": "Metabolic syndrome is a constellation of interrelated risk factors of metabolic origin including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, elevated plasma glucose level, and prothrombotic and proinflammatory states that promote atherosclerotic CVD and increase the risk of type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17125447", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 871, "text": "The waist circumference cut points for diagnosing metabolic syndrome (as defined using the new harmonised guidelines), insulin resistance, dysglycaemia, hypertension and dyslipidaemia were obtained using receiver operator characteristic curve analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23145009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The metabolic syndrome is a complex association of several risk factors including insulin resistance, dyslipidemia, and essential hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11276389", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 831, "text": " insulin resistance syndrome (often referred to as syndrome X or the metabolic syndrome) ie, a clustering of metabolic, atheromatous risk factors, including hypertriglyceridaemia, hyperinsulinaemia, hyper-tension, hypercholesterinaemia and obesity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12148078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "The metabolic syndrome is a clustering of risk factors which predispose an individual to cardiovascular morbidity and mortality. There is general consensus regarding the main components of the syndrome (glucose intolerance, obesity, raised blood pressure and dyslipidaemia [elevated triglycerides, low levels of high-density lipoprotein cholesterol]) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17469041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Metabolic syndrome (MS) refers to the clustering of cardiometabolic risk factors - including abdominal obesity, hyperglycaemia, dyslipidaemia and elevated blood pressure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17137436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The metabolic syndrome is a constellation of risk factors including glucose dysregulation, central obesity, dyslipidemia, and hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18497723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 506, "text": "Insulin resistance syndrome (IRS), also termed syndrome X, is a distinctive constellation of risk factors for the development of type 2 diabetes mellitus and cardiovascular disease. The syndrome's hallmarks are glucose intolerance, hyperinsulinemia, a characteristic dyslipidemia (high triglycerides; low high-density lipoprotein cholesterol, and small, dense low-density lipoprotein cholesterol), obesity, upper-body fat distribution, hypertension, and increased prothrombotic and antifibrinolytic factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10682170", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "\"The metabolic syndrome\" is the name for a clustering of risk factors for cardiovascular disease and type 2 diabetes that are of metabolic origin. These risk factors consist of atherogenic dyslipidemia, elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16762931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Metabolic Syndrome X is a clinical entity which comprises the following factors: diabetes mellitus, arterial hypertension, high levels of triglyceride and/or low levels of HDL cholesterol, central obesity and microalbuminuria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12137304", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 693, "text": "metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10863169", "endSection": "abstract" } ] }, { "body": "Silent Allosteric Modulation of mGluR5 is a form of treatment for what disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28683325", "http://www.ncbi.nlm.nih.gov/pubmed/25148681" ], "ideal_answer": [ "silent allosteric modulation of mGluR5 has promise as a disease-modifying AD intervention with a broad therapeutic window. ", "silent allosteric modulation of mGluR5 has promise as a disease-modifying AD intervention with a broad therapeutic window.", "Silent allosteric modulation of mGluR5 has promise as a disease-modifying Alzheimer's Disease therapy." ], "exact_answer": [ "Alzheimer's disease" ], "type": "factoid", "id": "5a8715a961bb38fb24000006", "snippets": [ { "offsetInBeginSection": 931, "offsetInEndSection": 1053, "text": "silent allosteric modulation of mGluR5 has promise as a disease-modifying AD intervention with a broad therapeutic window.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683325", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1374, "text": "In brain homogenates with A\u03b2o, the interaction of PrP(C) and mGluR5 is reversed by mGluR5-directed antagonists or antibodies directed against the PrP(C) segment of amino acids 91-153. Silent allosteric modulators of mGluR5 do not alter Glu or basal mGluR5 activity, but they disrupt the A\u03b2o-induced interaction of mGluR5 with PrP(C)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25148681", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1645, "text": "The assays described here have the potential to identify and develop new compounds that inhibit the interaction of PrP(C) and mGluR5, which plays a pivotal role in the pathogenesis of Alzheimer disease by transmitting the signal from extracellular A\u03b2o into the cytosol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25148681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer's Mouse Phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683325", "endSection": "title" }, { "offsetInBeginSection": 813, "offsetInEndSection": 1052, "text": "Our data show that mGluR5's role in A\u03b2o-dependent AD phenotypes is separate from its role in glutamate signaling and silent allosteric modulation of mGluR5 has promise as a disease-modifying AD intervention with a broad therapeutic window.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683325", "endSection": "abstract" } ] }, { "body": "What are check point inhibitors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24485523", "http://www.ncbi.nlm.nih.gov/pubmed/27403706", "http://www.ncbi.nlm.nih.gov/pubmed/28363334", "http://www.ncbi.nlm.nih.gov/pubmed/26942589", "http://www.ncbi.nlm.nih.gov/pubmed/27528363", "http://www.ncbi.nlm.nih.gov/pubmed/28878676", "http://www.ncbi.nlm.nih.gov/pubmed/26321371", "http://www.ncbi.nlm.nih.gov/pubmed/28351171", "http://www.ncbi.nlm.nih.gov/pubmed/27654928", "http://www.ncbi.nlm.nih.gov/pubmed/28865357" ], "ideal_answer": [ "Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology. These mAbs do not directly attack the malignant cells as most anticancer mAbs; rather, they enhance the anti-tumor response of the immune system by targeting immune regulatory pathways." ], "exact_answer": [ "monoclonal antibody drugs that regulate the immune response to cancer" ], "type": "factoid", "id": "5a8718c861bb38fb24000008", "snippets": [ { "offsetInBeginSection": 489, "offsetInEndSection": 795, "text": " Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology. These mAbs do not directly attack the malignant cells as most anticancer mAbs; rather, they enhance the anti-tumor response of the immune system by targeting immune regulatory pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28363334", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 550, "text": " These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27654928", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 972, "text": "Immune check point inhibitors may be of critical importance for the design of future immunotherapy approaches in GBM management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27528363", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1071, "text": "Immune check-point inhibitors should be considered a promising treatment option in GBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27528363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Immune check-point inhibitors are now employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC), while combinations of different inhibitors are being evaluated in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28351171", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 423, "text": "Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28878676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The recent successes of immune check point targeting therapies in treating cancer patients has driven a resurgence of interest in targeting these pathways in chronically infected patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28865357", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 587, "text": "These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28878676", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 235, "text": "The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28878676", "endSection": "abstract" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1391, "text": "Check point inhibitors have promising activity in several solid tumors and have demonstrated a favorable toxicity profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26942589", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 320, "text": "The treatment of melanoma is evolving rapidly over the past few years. Patients with BRAFv600 mutations can be treated with a combination of a BRAF-inhibitor and an MEK-inhibitor. Patients with BRAF wild-type tumors and BRAFv600 mutated tumors can be treated with immunotherapy i.e. check point inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27403706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Till now, the prognosis of advanced gastric cancer looked dreadful; thus the search for newer better approaches for this lethal disease has been a strategic target for cancer researchers. In recent years, important immunobiological aspects of the tumor have been revealed with the subsequent proposal of immune check point inhibitors to target these pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26321371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 486, "text": "Inhibitory receptors on immune system cells respond to membrane-bound and soluble ligands to abort or mitigate the intensity of immune responses by raising thresholds of activation, halting proliferation, favoring apoptosis or inhibiting/deviating effector function differentiation. Such evolutionarily selected inhibitory mechanisms are termed check-points and therefore check-point inhibitors empower any ongoing anti-cancer immune response that might have been too weak or exhausted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24485523", "endSection": "abstract" } ] }, { "body": "Are the human bombesin receptors, GRPR and NMBR, frequently overexpressed G-protein-coupled-receptors by lung-cancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25554218", "http://www.ncbi.nlm.nih.gov/pubmed/18975117", "http://www.ncbi.nlm.nih.gov/pubmed/20438784", "http://www.ncbi.nlm.nih.gov/pubmed/10545285", "http://www.ncbi.nlm.nih.gov/pubmed/21060250", "http://www.ncbi.nlm.nih.gov/pubmed/22828605" ], "ideal_answer": [ "The human bombesin receptors, GRPR and NMBR, are two of the most frequently overexpressed G-protein-coupled-receptors by lung-cancers", "All 3 bombesin receptor subtypes (GRPR, NMBR, and BRS-3) were present on pulmonary and intestinal carcinoids by immunohistochemistry. " ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D018004", "https://meshb.nlm.nih.gov/record/ui?ui=D008175" ], "type": "yesno", "id": "5a8dc57ffcd1d6a10c000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Members of the gastrin-releasing peptide (GRP) family and its analogs bombesin (BBN) have been implicated in the biology of several human cancers including prostate, breast, colon and lung.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18975117", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 974, "text": "All 3 bombesin receptor subtypes (GRPR, NMBR, and BRS-3) were present on pulmonary and intestinal carcinoids by immunohistochemistry", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21060250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "There is increased interest in the Bn-receptor family because they are frequently over/ectopically expressed by tumors and thus useful as targets for imaging or receptor-targeted-cytotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25554218", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Gastrin-releasing peptide (GRP), a member of the bombesin family of peptides, has been shown to have mitogenic activity in small cell lung carcinoma (SCLC), and to be produced by SCLC in an autocrine fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545285", "endSection": "abstract" } ] }, { "body": "Which data simulator is available for CLIP-SEQ experiments?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26776207" ], "ideal_answer": [ "CLIP-Seq protocols such as PAR-CLIP, HITS-CLIP or iCLIP allow a genome-wide analysis of protein-RNA interactions. For the processing of the resulting short read data, various tools are utilized. Some of these tools were specifically developed for CLIP-Seq data, whereas others were designed for the analysis of RNA-Seq data. To this date, however, it has not been assessed which of the available tools are most appropriate for the analysis of CLIP-Seq data. This is because an experimental gold standard dataset on which methods can be accessed and compared, is still not available. To address this lack of a gold-standard dataset, Cseq-Simulator was developed as a simulator for PAR-CLIP, HITS-CLIP and iCLIP-data. This simulator can be applied to generate realistic datasets that can serve as surrogates for experimental gold standard dataset." ], "exact_answer": [ "Cseq-Simulator" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D059014", "https://meshb.nlm.nih.gov/record/ui?ui=D017423" ], "type": "factoid", "id": "5a75f6e083b0d9ea66000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "CSEQ-SIMULATOR: A DATA SIMULATOR FOR CLIP-SEQ EXPERIMENTS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26776207", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1150, "text": "CLIP-Seq protocols such as PAR-CLIP, HITS-CLIP or iCLIP allow a genome-wide analysis of protein-RNA interactions. For the processing of the resulting short read data, various tools are utilized. Some of these tools were specifically developed for CLIP-Seq data, whereas others were designed for the analysis of RNA-Seq data. To this date, however, it has not been assessed which of the available tools are most appropriate for the analysis of CLIP-Seq data. This is because an experimental gold standard dataset on which methods can be accessed and compared, is still not available. To address this lack of a gold-standard dataset, we here present Cseq-Simulator, a simulator for PAR-CLIP, HITS-CLIP and iCLIP-data. This simulator can be applied to generate realistic datasets that can serve as surrogates for experimental gold standard dataset. In this work, we also show how Cseq-Simulator can be used to perform a comparison of steps of typical CLIP-Seq analysis pipelines, such as the read alignment or the peak calling. These comparisons show which tools are useful in different settings and also allow identifying pitfalls in the data analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26776207", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1024, "text": "In this work, we also show how Cseq-Simulator can be used to perform a comparison of steps of typical CLIP-Seq analysis pipelines, such as the read alignment or the peak calling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26776207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "CSEQ-SIMULATOR: A DATA SIMULATOR FOR CLIP-SEQ EXPERIMENTS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26776207", "endSection": "title" } ] }, { "body": "Falciform ligament sign is characteristic to which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2003436", "http://www.ncbi.nlm.nih.gov/pubmed/15471663", "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "http://www.ncbi.nlm.nih.gov/pubmed/17913427" ], "ideal_answer": [ "The falciform ligament sign (gas outlining the falciform ligament) is characteristic to pneumoperitoneum due to intestinal perforation." ], "exact_answer": [ "pneumoperitoneum" ], "type": "factoid", "id": "5a72329e2dc08e987e000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "What determines the periportal free air, and ligamentum teres and falciform ligament signs on CT: can these specific air distributions be valuable predictors of gastroduodenal perforation?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "PURPOSE: The purpose of this retrospective study was to determine what gives rise to the periportal free air, and ligamentum teres and falciform ligament signs on CT in patients with gastrointestinal (GI) tract perforation, and whether these specific air distributions can play a clinically meaningful role in the diagnosis of gastroduodenal perforation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 636, "text": "The readers assessed the presence of specific air distributions on CT (periportal free air, and ligamentum teres and falciform ligament signs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1376, "text": "RESULTS: All specific air distributions were more frequently present in patients with gastroduodenal perforation than lower GI tract perforation, but only the falciform ligament sign was statistically significant (p<0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1743, "text": "Regardless of the perforation sites, the falciform ligament sign was present significantly more frequently with an increase in the amount of free air on multiple logistic regression analysis (adjusted odds ratio, 1.29; p<0.001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 972, "text": "To evaluate the usefulness of the PPFA sign, we compared the PPFA sign with the falciform ligament sign and the ligamentum teres sign, both of which are well-known CT signs of pneumoperitoneum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17913427", "endSection": "abstract" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1723, "text": "The falciform ligament sign was seen in 24 of 30 (80%) patients with upper GI tract perforation and in 10 of 23 (43%) patients with lower GI tract perforation (p=.020). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17913427", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 697, "text": "Supine films from 44 cases of pneumoperitoneum were randomly interspersed among supine films from 87 control subjects without free air, and the films were reviewed for the presence or absence of various signs of pneumoperitoneum, including Rigler's sign (gas on both sides of the bowel wall), the falciform ligament sign (gas outlining the falciform ligament), the football sign (gas outlining the peritoneal cavity), the inverted-V sign (gas outlining the medial umbilical folds), and the right-upper-quadrant gas sign (localized gas in the right upper quadrant). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2003436", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 606, "text": "Forty-two patients with 10 cases of proximal GI perforation and 32 cases of distal GI perforation were evaluated based on the CT findings of extraluminal air (which was subdivided into the CT-falciform ligament sign crossing the midline and scattered pockets of air), bowel wall thickening (>8 mm in gastroduodenal wall,>3 mm in the small bowel wall,>6 mm in the caliber of the appendix and>5 mm in the colonic wall), associated abscess formation, ascites and adjacent fat stranding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15471663", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 1051, "text": "Our results showed that CT-falciform ligament sign was more frequent in the proximal GI perforation, while pockets of extraluminal air (excluding the cases accompanying CT-falciform ligament sign), bowel wall thickening and fat stranding were found in higher incidence in distal GI perforation (P<.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15471663", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 1053, "text": "Our results showed that CT-falciform ligament sign was more frequent in the proximal GI perforation, while pockets of extraluminal air (excluding the cases accompanying CT-falciform ligament sign), bowel wall thickening and fat stranding were found in higher incidence in distal GI perforation (P<.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15471663", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 354, "text": "The purpose of this retrospective study was to determine what gives rise to the periportal free air, and ligamentum teres and falciform ligament signs on CT in patients with gastrointestinal (GI) tract perforation, and whether these specific air distributions can play a clinically meaningful role in the diagnosis of gastroduodenal perforation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "endSection": "abstract" }, { "offsetInBeginSection": 2037, "offsetInEndSection": 2139, "text": "The PPFA sign is a useful finding which can help to distinguish upper from lower GI tract perforation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17913427", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 696, "text": "Supine films from 44 cases of pneumoperitoneum were randomly interspersed among supine films from 87 control subjects without free air, and the films were reviewed for the presence or absence of various signs of pneumoperitoneum, including Rigler's sign (gas on both sides of the bowel wall), the falciform ligament sign (gas outlining the falciform ligament), the football sign (gas outlining the peritoneal cavity), the inverted-V sign (gas outlining the medial umbilical folds), and the right-upper-quadrant gas sign (localized gas in the right upper quadrant).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2003436", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 940, "text": "To evaluate the usefulness of the PPFA sign, we compared the PPFA sign with the falciform ligament sign and the ligamentum teres sign, both of which are well-known CT signs of pneumoperitoneum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17913427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "What determines the periportal free air, and ligamentum teres and falciform ligament signs on CT: can these specific air distributions be valuable predictors of gastroduodenal perforation?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19716250", "endSection": "title" } ] }, { "body": "Is vorinostat effective for glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29016887", "http://www.ncbi.nlm.nih.gov/pubmed/22090453", "http://www.ncbi.nlm.nih.gov/pubmed/22923449", "http://www.ncbi.nlm.nih.gov/pubmed/24838514", "http://www.ncbi.nlm.nih.gov/pubmed/29133513", "http://www.ncbi.nlm.nih.gov/pubmed/24576944", "http://www.ncbi.nlm.nih.gov/pubmed/22028388" ], "ideal_answer": [ "No. Although vorinostat is well tolerated it does not improve survival of glioblastoma patients." ], "exact_answer": "no", "type": "yesno", "id": "5a7615af83b0d9ea6600001f", "snippets": [ { "offsetInBeginSection": 1630, "offsetInEndSection": 1906, "text": "Conclusions: Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29016887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29133513", "endSection": "abstract" }, { "offsetInBeginSection": 1772, "offsetInEndSection": 1961, "text": "CONCLUSION: Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29133513", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1042, "text": "We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24576944", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1289, "text": "Vorinostat is the most advanced HDAC inhibitor that entered clinical trials in glioblastoma, showing activity in recurrent disease. Multiple phase II trials with vorinostat in combination with targeted agents, temozolomide and radiotherapy are currently recruiting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24838514", "endSection": "abstract" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1601, "text": ". On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090453", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1552, "text": "ith the increased toxicities associated with CPT-11 coupled with its unclear clinical significance, investigating the efficacy of vorinostat combined with bevacizumab alone may represent a more promising strategy to evaluate in the context of a phase II clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028388", "endSection": "abstract" }, { "offsetInBeginSection": 1426, "offsetInEndSection": 1637, "text": "CONCLUSION: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22923449", "endSection": "abstract" } ] }, { "body": "Is there any role of Dlx1 and Dlx2 transcription factors in cortical interneurons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028947" ], "ideal_answer": [ "Yes. DLX2 directly drives Gad1, Gad2, and Vgat expression, and mutants have reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and have reduced mIPSC frequency. Furthermore, Dlx1/2 CKO have hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/DLX2_RAT", "http://www.uniprot.org/uniprot/DLX2A_DANRE", "http://www.uniprot.org/uniprot/DLX2_ELECQ", "http://www.uniprot.org/uniprot/DLX2_HUMAN", "http://www.uniprot.org/uniprot/DLX1_MOUSE", "http://www.uniprot.org/uniprot/DLX1_HUMAN", "http://www.uniprot.org/uniprot/DLX2_MOUSE", "http://www.uniprot.org/uniprot/DLX1_RAT", "https://meshb.nlm.nih.gov/record/ui?ui=D014157" ], "type": "yesno", "id": "5a6d186db750ff4455000031", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 931, "text": "The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency. Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input. We provide evidence that some of these phenotypes were due to reduced expression of GRIN2B (a subunit of the NMDA receptor), a high confidence Autism gene. Thus, Dlx1&2 coordinate key components of CIN postnatal development by promoting their excitability, inhibitory output, and survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028947", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 641, "text": "Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028947", "endSection": "abstract" } ] }, { "body": "Describe SNP2TFBS", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27899579" ], "ideal_answer": [ "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/.", "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs." ], "type": "summary", "id": "5a6a7869b750ff4455000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1101, "text": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 1101, "text": "These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1057, "text": "SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "title" } ] }, { "body": "What is SMiLE-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28092692" ], "ideal_answer": [ "Selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq) is a semiautomated protein-DNA interaction characterization technology. SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion.", "SMiLE-Seq is a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing for de novo transcription factor motif discovery.", "Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. All tested TFs yielded DNA-binding models with predictive power comparable to or greater than that of other in vitro assays.", "Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. We validated SMiLE-seq by analyzing 58 full-length human, mouse, and Drosophila TFs from distinct structural classes. All tested TFs yielded DNA-binding models with predictive power comparable to or greater than that of other in vitro assays. De novo motif discovery on all JUN-FOS heterodimers and several nuclear receptor-TF complexes provided novel insights into partner-specific heterodimer DNA-binding preferences." ], "type": "summary", "id": "5a6cfe27b750ff4455000029", "snippets": [ { "offsetInBeginSection": 127, "offsetInEndSection": 923, "text": "Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. We validated SMiLE-seq by analyzing 58 full-length human, mouse, and Drosophila TFs from distinct structural classes. All tested TFs yielded DNA-binding models with predictive power comparable to or greater than that of other in vitro assays. De novo motif discovery on all JUN-FOS heterodimers and several nuclear receptor-TF complexes provided novel insights into partner-specific heterodimer DNA-binding preferences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "SMiLE-seq identifies binding motifs of single and dimeric transcription factors", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092692", "endSection": "title" }, { "offsetInBeginSection": 304, "offsetInEndSection": 503, "text": "SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092692", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 302, "text": "Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092692", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 303, "text": "Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092692", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 621, "text": "We validated SMiLE-seq by analyzing 58 full-length human, mouse, and Drosophila TFs from distinct structural classes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "SMiLE-seq identifies binding motifs of single and dimeric transcription factors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092692", "endSection": "title" } ] }, { "body": "What is libgapmis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24564250" ], "ideal_answer": [ "libgapmis is a library for extending pairwise short-read alignments. Apart from the standard CPU version, it includes ultrafast SSE- and GPU-based implementations. libgapmis is based on an algorithm computing a modified version of the traditional dynamic-programming matrix for sequence alignment. The open-source code of libgapmis is available at http://www.exelixis-lab.org/gapmis." ], "type": "summary", "id": "5a6a35b7b750ff4455000027", "snippets": [ { "offsetInBeginSection": 1077, "offsetInEndSection": 1372, "text": "libgapmis, a library for extending pairwise short-read alignments. Apart from the standard CPU version, it includes ultrafast SSE- and GPU-based implementations. libgapmis is based on an algorithm computing a modified version of the traditional dynamic-programming matrix for sequence alignment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1951, "offsetInEndSection": 2370, "text": "We present libgapmis, a library for extending pairwise short-read alignments. We show that libgapmis is better-suited and more efficient than existing algorithms for this task. The importance of our contribution is underlined by the fact that the provided functions may be seamlessly integrated into any short-read alignment pipeline. The open-source code of libgapmis is available at http://www.exelixis-lab.org/gapmis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1390, "text": "libgapmis is based on an algorithm computing a modified version of the traditional dynamic-programming matrix for sequence alignment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1161, "text": "The fact that the reads are rather short and that the gap occurrence frequency observed in various studies is rather low suggest that aligning (parts of) those reads with a single gap is in fact desirable.
RESULTS: In this article, we present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1953, "offsetInEndSection": 2030, "text": "We present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1144, "text": "In this article, we present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1942, "offsetInEndSection": 2031, "text": "CONCLUSIONS We present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1144, "text": "RESULTS In this article, we present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1718, "offsetInEndSection": 2057, "text": "The library also provides the user the flexibility to split the read into fragments, based on the observed gap occurrence frequency and the length of the read, thereby allowing for a variable, but bounded, number of gaps in the alignment.
CONCLUSIONS: We present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1919, "offsetInEndSection": 1996, "text": "We present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1123, "text": "In this article, we present libgapmis, a library for extending pairwise short-read alignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564250", "endSection": "abstract" } ] }, { "body": "Has ATF4 transcription factor been linked to cancer and neoplastic transformation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17297441", "http://www.ncbi.nlm.nih.gov/pubmed/27211800", "http://www.ncbi.nlm.nih.gov/pubmed/28797581", "http://www.ncbi.nlm.nih.gov/pubmed/25883982", "http://www.ncbi.nlm.nih.gov/pubmed/22102693", "http://www.ncbi.nlm.nih.gov/pubmed/24681956", "http://www.ncbi.nlm.nih.gov/pubmed/28843961", "http://www.ncbi.nlm.nih.gov/pubmed/17466566" ], "ideal_answer": [ "Yes, ATF4 transcription factor has been linked to cancer and neoplastic transformation." ], "exact_answer": "yes", "concepts": [ "http://www.uniprot.org/uniprot/ATF4_BOVIN", "http://www.uniprot.org/uniprot/ATF4_RAT", "http://www.biosemantics.org/jochem#4250481", "https://meshb.nlm.nih.gov/record/ui?ui=D051701" ], "type": "yesno", "id": "5a773c50faa1ab7d2e000002", "snippets": [ { "offsetInBeginSection": 1367, "offsetInEndSection": 1603, "text": "aken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681956", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 708, "text": "s a result, the level of phosphorylated Eukaryotic Initiation Factor 2 alpha (eIF2\u03b1) is markedly elevated, resulting in the promotion of a pro-adaptive signaling pathway by the inhibition of global protein synthesis and selective translation of Activating Transcription Factor 4 (ATF4). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27211800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "Many cancers overexpress ATF4, a stress-induced transcription factor that promotes cell survival under hypoxic conditions and other stresses of the tumor microenvironment, but the potential contributions of ATF4 to oncogenesis itself have been little explored. Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102693", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 409, "text": "Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102693", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 888, "text": "Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102693", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1159, "text": "Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102693", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1012, "text": "ATF4 expression is upregulated in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17466566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Activating transcription factor 4 (ATF4), an endoplasmic reticulum stress-inducible transcription factor, plays important roles in cancer progression and resistance to therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28843961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28797581", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1155, "text": "Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Stress-regulated transcription factor ATF4 promotes neoplastic transformation by suppressing expression of the INK4a/ARF cell senescence factors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102693", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 379, "text": "Activating transcription factor 4 (ATF4), a member of the ATF/CREB family, has been reported to be related to tumor angiogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25883982", "endSection": "abstract" } ] }, { "body": "Are patients with Sjogren syndrome at increased risk for lymphoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/529328", "http://www.ncbi.nlm.nih.gov/pubmed/28779180", "http://www.ncbi.nlm.nih.gov/pubmed/22208651", "http://www.ncbi.nlm.nih.gov/pubmed/24159176", "http://www.ncbi.nlm.nih.gov/pubmed/19745687", "http://www.ncbi.nlm.nih.gov/pubmed/23845207", "http://www.ncbi.nlm.nih.gov/pubmed/17992593", "http://www.ncbi.nlm.nih.gov/pubmed/27336863", "http://www.ncbi.nlm.nih.gov/pubmed/17408137", "http://www.ncbi.nlm.nih.gov/pubmed/12886135", "http://www.ncbi.nlm.nih.gov/pubmed/21172862", "http://www.ncbi.nlm.nih.gov/pubmed/21805176", "http://www.ncbi.nlm.nih.gov/pubmed/24153350", "http://www.ncbi.nlm.nih.gov/pubmed/1608349", "http://www.ncbi.nlm.nih.gov/pubmed/22497865", "http://www.ncbi.nlm.nih.gov/pubmed/26998372", "http://www.ncbi.nlm.nih.gov/pubmed/12064854", "http://www.ncbi.nlm.nih.gov/pubmed/17119030", "http://www.ncbi.nlm.nih.gov/pubmed/21842694", "http://www.ncbi.nlm.nih.gov/pubmed/10414252" ], "ideal_answer": [ "Yes, the heightened risk of non-Hodgkin lymphoma (NHL) development in primary Sjogren syndrome is well established. Five per cent of patients with primary Sjogren's syndrome develop malignant non-Hodgkin's lymphoma, usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. The incidence of lymphoma is higher in patients with Sj\u00f6gren's syndrome than in the general population." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D012859", "https://meshb.nlm.nih.gov/record/ui?ui=D008223", "https://meshb.nlm.nih.gov/record/ui?ui=D012306", "http://www.disease-ontology.org/api/metadata/DOID:12894" ], "type": "yesno", "id": "5a6f87c5b750ff4455000056", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The heightened risk of non-Hodgkin lymphoma (NHL) development in primary Sjogren syndrome (SS) is well established.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27336863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26998372", "endSection": "title" }, { "offsetInBeginSection": 677, "offsetInEndSection": 794, "text": "Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26998372", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1418, "text": "To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26998372", "endSection": "abstract" }, { "offsetInBeginSection": 638, "offsetInEndSection": 792, "text": "Rituximab is also effective in the treatment of SS-associated (extrasalivary) lymphomas, although the therapeutic response in salivary lymphoma is poorer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22497865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Rituximab treatment for Sjogren syndrome-associated non-Hodgkin's lymphoma: case series.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21805176", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Five per cent of patients with primary Sjogren's syndrome (pSS) develop malignant non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21805176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "[A case of Sjogren syndrome coexistent with MALT lymphoma occurring along the parotid gland and trachea].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21842694", "endSection": "title" }, { "offsetInBeginSection": 524, "offsetInEndSection": 605, "text": "Both histological examinations revealed MALT-type marginal zone B-cell lymphoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21842694", "endSection": "abstract" }, { "offsetInBeginSection": 1620, "offsetInEndSection": 1757, "text": "In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21172862", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 956, "text": "The incidence of lymphoma is higher in patients with Sj\u00f6gren's syndrome than in the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17408137", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1225, "text": "Among the clinical and serological parameters that have been associated with lymphoma development in SS patients, the presence of palpable purpura, low C4, and mixed monoclonal cryoglobulinemia constitute the main predictive markers, and patients displaying these risk factors should be monitored closely.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17992593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "A case of pulmonary pseudolymphoma and Sjogren syndrome is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/529328", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1629, "text": "Furthermore, RA, Sj\u00f6gren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sj\u00f6gren's syndrome with risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Predicting the risk for lymphoma development in Sjogren syndrome: An easy tool for clinical use.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27336863", "endSection": "title" }, { "offsetInBeginSection": 15, "offsetInEndSection": 162, "text": "Lymphoma is a very severe complication of primary Sj\u00f6gren's syndrome: 5 to 10% of patients followed for more than 10 years will develop a lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10414252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Hematologic manifestations and predictors of lymphoma development in primary Sj\u00f6gren syndrome: clinical and pathophysiologic aspects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19745687", "endSection": "title" }, { "offsetInBeginSection": 889, "offsetInEndSection": 1024, "text": "Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sj\u00f6gren's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Several autoimmune diseases, including primary Sj\u00f6gren's syndrome (pSS), are associated with an increased risk for lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24159176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Primary Sjogren's syndrome (pSS) confers increased risk for non-Hodgkin lymphoma (NHL) development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28779180", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1589, "text": "Furthermore, we review the emerging role of ELS and lymphoid chemokines in driving extranodal B cell lymphomagenesis in SS and we focus on recent evidence suggesting that ELS identify subsets of SS patients at increased risk of developing systemic manifestations and lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22208651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Sjogren's syndrome (SS) is a chronic autoimmune disorder with the highest risk for lymphoma development among all autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153350", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 417, "text": "In contrast to secondary SS, the risk for developing non-Hodgkin's lymphoma is highly increased in patients with primary SS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12064854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Predicting the risk for lymphoma development in Sjogren syndrome: An easy tool for clinical use.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27336863", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Primary Sjogren's syndrome (pSS) is complicated by B-cell lymphoma in 5-10% of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845207", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1164, "text": "Patients with Sj\u00f6gren syndrome are at increased risk of lymphoma development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12886135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Sjogren's syndrome is an autoimmune disease with a known predisposition for lymphoma development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1608349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Certain autoimmune and chronic inflammatory conditions, such as Sj\u00f6gren's syndrome and rheumatoid arthritis (RA), have consistently been associated with an increased risk of malignant lymphomas, but it is unclear whether elevated lymphoma risk is a phenomenon that accompanies inflammatory conditions in general.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119030", "endSection": "abstract" } ] }, { "body": "Describe JACUSA", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28049429" ], "ideal_answer": [ "JACUSA detects single nucleotide variants by comparing data from next-generation sequencing experiments (RNA-DNA or RNA-RNA). In practice, JACUSA shows higher recall and comparable precision in detecting A\u2192I sites from RNA-DNA comparisons, while showing higher precision and recall in RNA-RNA comparisons." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D017393" ], "type": "summary", "id": "5a75f5aa83b0d9ea66000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "JACUSA: site-specific identification of RNA editing events from replicate sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "title" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1964, "text": "We present JACUSA, a versatile one-stop solution to detect single nucleotide variant positions from comparing RNA-DNA and/or RNA-RNA sequencing samples. The performance of JACUSA has been carefully evaluated and compared to other variant callers in an in silico benchmark. JACUSA outperforms other algorithms in terms of the F measure, which combines precision and recall, in all benchmark scenarios. This performance margin is highest for the RNA-RNA comparison scenario. We further validated JACUSA's performance by testing its ability to detect A\u2192I events using sequencing data from a human cell culture experiment and publicly available RNA-seq data from Drosophila melanogaster heads. To this end, we performed whole genome and RNA sequencing of HEK-293 cells on samples with lowered activity of candidate RNA editing enzymes. JACUSA has a higher recall and comparable precision for detecting true editing sites in RDD comparisons of HEK-293 data. Intriguingly, JACUSA captures most A\u2192I events from RRD comparisons of RNA sequencing data derived from Drosophila and HEK-293 data sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "abstract" }, { "offsetInBeginSection": 1976, "offsetInEndSection": 2294, "text": "Our software JACUSA detects single nucleotide variants by comparing data from next-generation sequencing experiments (RNA-DNA or RNA-RNA). In practice, JACUSA shows higher recall and comparable precision in detecting A\u2192I sites from RNA-DNA comparisons, while showing higher precision and recall in RNA-RNA comparisons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "abstract" }, { "offsetInBeginSection": 670, "offsetInEndSection": 1045, "text": "Even more surprising, condition-specific editing events, which would show up as differences in RNA-RNA comparisons (RRDs) and depend on particular cellular states, are rarely discussed in the literature.
RESULTS: We present JACUSA, a versatile one-stop solution to detect single nucleotide variant positions from comparing RNA-DNA and/or RNA-RNA sequencing samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "abstract" }, { "offsetInBeginSection": 1846, "offsetInEndSection": 2143, "text": "Intriguingly, JACUSA captures most A\u2192I events from RRD comparisons of RNA sequencing data derived from Drosophila and HEK-293 data sets.
CONCLUSION: Our software JACUSA detects single nucleotide variants by comparing data from next-generation sequencing experiments (RNA-DNA or RNA-RNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "abstract" }, { "offsetInBeginSection": 1974, "offsetInEndSection": 2123, "text": "CONCLUSION Our software JACUSA detects single nucleotide variants by comparing data from next-generation sequencing experiments (RNA-DNA or RNA-RNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1030, "text": "RESULTS We present JACUSA, a versatile one-stop solution to detect single nucleotide variant positions from comparing RNA-DNA and/or RNA-RNA sequencing samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1007, "text": "We present JACUSA, a versatile one-stop solution to detect single nucleotide variant positions from comparing RNA-DNA and/or RNA-RNA sequencing samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28049429", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Tezepelumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28583618", "http://www.ncbi.nlm.nih.gov/pubmed/28368013", "http://www.ncbi.nlm.nih.gov/pubmed/28877011" ], "ideal_answer": [ "Tezepelumab is human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP)." ], "type": "summary", "id": "5a722ccd2dc08e987e000003", "snippets": [ { "offsetInBeginSection": 541, "offsetInEndSection": 893, "text": "These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2blockers (fevipiprant and timapiprant). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28583618", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 881, "text": "We further show that the monoclonal antibody Tezepelumab partly exploits these principles to neutralize TSLP activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368013", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 492, "text": "This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28877011", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 480, "text": "This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28877011", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 691, "text": "This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.
METHODS: In this phase 2, randomized, double-blind, placebo-controlled trial, we compared subcutaneous tezepelumab at three dose levels with placebo over a 52-week treatment period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28877011", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 852, "text": "These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28583618", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 491, "text": "This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28877011", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 856, "text": "These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28583618", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 892, "text": "These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D blockers (fevipiprant and timapiprant).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28583618", "endSection": "abstract" } ] }, { "body": "What is the association between kidney donation risk of gestational complications?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27591246", "http://www.ncbi.nlm.nih.gov/pubmed/8990390", "http://www.ncbi.nlm.nih.gov/pubmed/26090646", "http://www.ncbi.nlm.nih.gov/pubmed/19353771" ], "ideal_answer": [ "Kidney donation seems to elevate the risks of gestational complications. Postdonation pregnancies were associated with a higher risk of gestational diabetes, gestational hypertension, proteinuria and preeclampsia. However, others reported that donor nephrectomy is not detrimental to the prenatal course or outcome of future pregnancies." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001244", "https://meshb.nlm.nih.gov/record/ui?ui=D011248" ], "type": "summary", "id": "5a6f941eb750ff445500005b", "snippets": [ { "offsetInBeginSection": 831, "offsetInEndSection": 965, "text": "Pregnancies in donors may incur attributable risk of gestational hypertension or preeclampsia (11% versus 5% incidence in one study). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591246", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 551, "text": "Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26090646", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 1053, "text": "Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p<0.0001), proteinuria (4.3% vs. 1.1%, p<0.0001) and preeclampsia (5.5% vs. 0.8%, p<0.0001). Women who had both pre- and post-donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19353771", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 568, "text": "Complications incurred during gestation included miscarriage (13.3%), preeclampsia (4.4%), gestational hypertension (4.4%), proteinuria (4.4%), and tubal pregnancy (2.2%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8990390", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1207, "text": "Based on these results, we conclude that donor nephrectomy is not detrimental to the prenatal course or outcome of future pregnancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8990390", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 964, "text": "Pregnancies in donors may incur attributable risk of gestational hypertension or preeclampsia (11% versus 5% incidence in one study).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591246", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 551, "text": "Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26090646", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 550, "text": "Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26090646", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1311, "text": "In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19353771", "endSection": "abstract" } ] }, { "body": "Does prolactinoma increase osteoporosis risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26319389", "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "http://www.ncbi.nlm.nih.gov/pubmed/27446618", "http://www.ncbi.nlm.nih.gov/pubmed/20205855", "http://www.ncbi.nlm.nih.gov/pubmed/26243714", "http://www.ncbi.nlm.nih.gov/pubmed/17578827", "http://www.ncbi.nlm.nih.gov/pubmed/25472533", "http://www.ncbi.nlm.nih.gov/pubmed/15816365", "http://www.ncbi.nlm.nih.gov/pubmed/21479837", "http://www.ncbi.nlm.nih.gov/pubmed/11293923", "http://www.ncbi.nlm.nih.gov/pubmed/23965473", "http://www.ncbi.nlm.nih.gov/pubmed/9550540" ], "ideal_answer": [ "Yes, prolactinomas increase risk of osteoporosis. Prolactinomas also cause hypogonadism, infertility, and tumor mass effects." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D010024", "http://www.disease-ontology.org/api/metadata/DOID:5394", "https://meshb.nlm.nih.gov/record/ui?ui=D015175", "https://meshb.nlm.nih.gov/record/ui?ui=D012306" ], "type": "yesno", "id": "5a70d43b99e2c3af26000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Prolactinoma: A Massive Effect on Bone Mineral Density in a Young Patient.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27446618", "endSection": "title" }, { "offsetInBeginSection": 84, "offsetInEndSection": 456, "text": "Osteoporosis has been noted to be an issue in postmenopausal women with prolactinomas. This case shows a similar impact on bone health in a young male resulting in low bone mineral density for age based on Z-score. This case report highlights the possible mechanisms for the bone loss in the setting of prolactinoma and the need for assessing bone health in such patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27446618", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1181, "text": " Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26319389", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 354, "text": "Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26243714", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 350, "text": "Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25472533", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 733, "text": "We present a 22-year-old man with multiple osteoporotic fractures associated with prolactinoma despite the use of teriparatide for 18 months. We emphasize and highlight the importance of hyperprolactinemia and fractures caused by high prolactin levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23965473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "OBJECTIVE: Patients with prolactinoma seem to be at high risk for osteopenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 724, "text": "RESULTS: Compared to the matched controls, BMD of patients with prolactinoma or craniopharyngioma significantly decreased. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "endSection": "abstract" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1310, "text": "CONCLUSION: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Prolactinoma presenting as chronic anaemia with osteoporosis: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205855", "endSection": "title" }, { "offsetInBeginSection": 154, "offsetInEndSection": 374, "text": "Six years later, he was evaluated and diagnosed with a prolactinoma and resultant osteoporosis. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205855", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1327, "text": "The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11293923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "INTRODUCTION: Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578827", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1350, "text": "Univariate and multivariate regression analysis indicated that the bone loss in prolactinomas was significantly correlated to disease duration and hypogonadism.
CONCLUSION: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 873, "text": "High serum prolactin levels lead to increase of the risk of osteopenia or/and osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26319389", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 509, "text": "Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction.
CASE PRESENTATION: We describe the case of a 70-year-old Caucasian man who presented with mild anaemia and tiredness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205855", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1313, "text": "In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1323, "text": "The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11293923", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1315, "text": "CONCLUSION In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 373, "text": "Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20205855", "endSection": "abstract" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1180, "text": "Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26319389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "INTRODUCTION Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578827", "endSection": "abstract" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1531, "text": "In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15816365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Humans with prolactinoma are at risk for osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9550540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578827", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1324, "text": "The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11293923", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1258, "text": "In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22553947", "endSection": "abstract" } ] }, { "body": "In November 2017, in what phase was the clinical trial for the drug SYL040012?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28389707" ], "ideal_answer": [ "SYL040012 is in phase 2 clinical trials" ], "exact_answer": [ "Phase 3" ], "type": "factoid", "id": "5a735cdc3b9d13c708000004", "snippets": [ { "offsetInBeginSection": 435, "offsetInEndSection": 728, "text": "This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials. The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389707", "endSection": "abstract" } ] }, { "body": "Describe the RNA Centric Annotation System (RCAS)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28334930" ], "ideal_answer": [ "The RNA Centric Annotation System (RCAS) is an R package which is designed to ease the process of creating gene-centric annotations and analysis for the genomic regions of interest obtained from various RNA-based omics technologies. The design of RCAS is modular, which enables flexible usage and convenient integration with other bioinformatics workflows. RCAS is an R/Bioconductor package but there are also graphical user interfaces including a Galaxy wrapper and a stand-alone web service. The application of RCAS on published datasets shows that RCAS is not only able to reproduce published findings but also helps generate novel knowledge and hypotheses. The meta-gene profiles, gene-centric annotation, motif analysis and gene-set analysis provided by RCAS provide contextual knowledge which is necessary for understanding the functional aspects of different biological events that involve RNAs. In addition, the array of different interfaces and deployment options adds the convenience of use for different levels of users. RCAS is available at http://bioconductor.org/packages/release/bioc/html/RCAS.html and http://rcas.mdc-berlin.de." ], "type": "summary", "id": "5a6fa417b750ff445500005f", "snippets": [ { "offsetInBeginSection": 288, "offsetInEndSection": 1449, "text": "Here, we present the RNA Centric Annotation System (RCAS), an R package, which is designed to ease the process of creating gene-centric annotations and analysis for the genomic regions of interest obtained from various RNA-based omics technologies. The design of RCAS is modular, which enables flexible usage and convenient integration with other bioinformatics workflows. RCAS is an R/Bioconductor package but we also created graphical user interfaces including a Galaxy wrapper and a stand-alone web service. The application of RCAS on published datasets shows that RCAS is not only able to reproduce published findings but also helps generate novel knowledge and hypotheses. The meta-gene profiles, gene-centric annotation, motif analysis and gene-set analysis provided by RCAS provide contextual knowledge which is necessary for understanding the functional aspects of different biological events that involve RNAs. In addition, the array of different interfaces and deployment options adds the convenience of use for different levels of users. RCAS is available at http://bioconductor.org/packages/release/bioc/html/RCAS.html and http://rcas.mdc-berlin.de.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334930", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 536, "text": "Here, we present the RNA Centric Annotation System (RCAS), an R package, which is designed to ease the process of creating gene-centric annotations and analysis for the genomic regions of interest obtained from various RNA-based omics technologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "RCAS: an RNA centric annotation system for transcriptome-wide regions of interest.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334930", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "RCAS: an RNA centric annotation system for transcriptome-wide regions of interest.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334930", "endSection": "title" } ] }, { "body": "What is Chronic Wasting Disease (CWD) in deer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18387626", "http://www.ncbi.nlm.nih.gov/pubmed/28109330", "http://www.ncbi.nlm.nih.gov/pubmed/17205898", "http://www.ncbi.nlm.nih.gov/pubmed/17951994", "http://www.ncbi.nlm.nih.gov/pubmed/29049389", "http://www.ncbi.nlm.nih.gov/pubmed/15148993", "http://www.ncbi.nlm.nih.gov/pubmed/21697479", "http://www.ncbi.nlm.nih.gov/pubmed/21918005", "http://www.ncbi.nlm.nih.gov/pubmed/16145200", "http://www.ncbi.nlm.nih.gov/pubmed/27549119", "http://www.ncbi.nlm.nih.gov/pubmed/1681473", "http://www.ncbi.nlm.nih.gov/pubmed/27575545", "http://www.ncbi.nlm.nih.gov/pubmed/27870037", "http://www.ncbi.nlm.nih.gov/pubmed/28193766", "http://www.ncbi.nlm.nih.gov/pubmed/28281927", "http://www.ncbi.nlm.nih.gov/pubmed/28250130", "http://www.ncbi.nlm.nih.gov/pubmed/11974617", "http://www.ncbi.nlm.nih.gov/pubmed/28139079", "http://www.ncbi.nlm.nih.gov/pubmed/22043912", "http://www.ncbi.nlm.nih.gov/pubmed/27641251", "http://www.ncbi.nlm.nih.gov/pubmed/17092889", "http://www.ncbi.nlm.nih.gov/pubmed/19901375", "http://www.ncbi.nlm.nih.gov/pubmed/26136567" ], "ideal_answer": [ "Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) affecting members of the cervid species, and is one of the few TSEs with an expanding geographic range." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D034081" ], "type": "summary", "id": "5a87140a61bb38fb24000003", "snippets": [ { "offsetInBeginSection": 200, "offsetInEndSection": 435, "text": "In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28250130", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 577, "text": "Of the known animal prion diseases, only bovine spongiform encephalopathy prions have been shown to be transmissible from animals to humans under non-experimental conditions. Chronic wasting disease (CWD) is a prion disease that affects cervids (e.g., deer and elk) in North America and isolated populations in Korea and Europe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Prion diseases, such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), and sheep scrapie, are caused by the misfolding of the cellular prion protein (PrPC) into a disease-causing conformer (PrPSc)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28109330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Chronic wasting disease (CWD), a prion disease of North American deer, elk and moose, affects both free-ranging and captive cervids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18387626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Chronic wasting disease (CWD) is an evolving prion disease of cervids (deer, elk and moose) that has been recognized in North America and Korea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21918005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy affecting white-tailed deer (Odocoileus virginianus), mule deer (Odocoileus hemionus), Rocky Mountain elk (Cervus elaphus nelsoni), and moose (Alces alces shirasi) in North America.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29049389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Chronic wasting disease (CWD) is an invariably fatal transmissible spongiform encephalopathy of white-tailed deer, mule deer, elk, and moose.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27575545", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Chronic wasting disease (CWD), a prion disease affecting North American cervids, has been discovered in at least 12 states and provinces throughout the continent.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19901375", "endSection": "title" }, { "offsetInBeginSection": 497, "offsetInEndSection": 665, "text": "The etiology of chronic wasting disease (CWD), a relatively new and burgeoning prion epidemic in deer, elk, and moose (members of the cervid family), is more enigmatic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28193766", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1160, "text": "Chronic wasting disease (CWD) is an emerging and uniformly fatal prion disease affecting free-ranging deer and elk and is now recognized in 22 U.S.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26136567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting free-ranging and captive cervids that now occurs in 24 U.S.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27870037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Chronic wasting disease (CWD) is a contagious, fatal prion disease affecting cervids in a growing number of regions across North America.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27549119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting North American cervids. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22043912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Prion diseases are neurodegenerative fatal disorders that affect human and non-human mammals. Chronic Wasting Disease (CWD) is a prion disease of cervids regarded as a public health problem in North America, and polymorphisms at specific codons in the PRNP gene are associated with this disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28281927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Chronic wasting disease (CWD) is a prion disease of cervids that causes neurodegeneration and death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21697479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Chronic wasting disease (CWD) has emerged as an important disease of wildlife in North America. The disease is a unique member of the transmissible spongiform encephalopathies (TSEs) or prion diseases, which naturally affect only a few species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11974617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Chronic wasting disease (CWD) is a fatal, emerging disease of cervids associated with transmissible protease-resistant prion proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17092889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Chronic wasting disease (CWD), a contagious prion disease of the deer family, has the potential to severely harm deer populations and disrupt ecosystems where deer occur in abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17205898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Chronic wasting disease (CWD) in cervids is one of the transmissible spongiform encephalopathies ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17951994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Chronic wasting disease (CWD) is a fatal contagious prion disease in cervids that is enzootic in some areas in North America. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Scrapie amyloid-immunoreactive plaques are present in brain tissues of captive mule deer with chronic wasting disease (CWD), a progressive neurological disorder characterized neuropathologically by widespread spongiform change of the neuropil, intracytoplasmic vacuolation in neuronal perikarya and astrocytic hypertrophy and hyperplasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1681473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Chronic wasting disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16145200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Chronic wasting disease (CWD) has recently emerged in North America as an important prion disease of captive and free-ranging cervids (species in the deer family). CWD is the only recognized transmissible spongiform encephalopathy (TSE) affecting free-ranging species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15148993", "endSection": "abstract" } ] }, { "body": "What does A1C measure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18030866", "http://www.ncbi.nlm.nih.gov/pubmed/21470266", "http://www.ncbi.nlm.nih.gov/pubmed/20807443", "http://www.ncbi.nlm.nih.gov/pubmed/20861123", "http://www.ncbi.nlm.nih.gov/pubmed/28964455", "http://www.ncbi.nlm.nih.gov/pubmed/21920547", "http://www.ncbi.nlm.nih.gov/pubmed/21737172", "http://www.ncbi.nlm.nih.gov/pubmed/22027330", "http://www.ncbi.nlm.nih.gov/pubmed/27522349", "http://www.ncbi.nlm.nih.gov/pubmed/27737895", "http://www.ncbi.nlm.nih.gov/pubmed/20923490", "http://www.ncbi.nlm.nih.gov/pubmed/26630892", "http://www.ncbi.nlm.nih.gov/pubmed/24511995", "http://www.ncbi.nlm.nih.gov/pubmed/15644138" ], "ideal_answer": [ "Glycated proteins, such as glycated hemoglobin (HbA1c) or glycated albumin (GA) in the blood, are essential indicators of glycemic control for diabetes mellitus. ", "The A1C measures the amount of glycated hemoglobin in the blood and is a marker for control of blood glucose. Poor glucose control is indicative of diabetes mellitus." ], "type": "summary", "id": "5a897927fcd1d6a10c00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Glycated proteins, such as glycated hemoglobin (HbA1c) or glycated albumin (GA) in the blood, are essential indicators of glycemic control for diabetes mellitus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27522349", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 149, "text": ": Monitoring of glycemic control with hemoglobin A1c(A1c) in hemodialysis patients may be compromised by anemia and erythropoietin therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27737895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BACKGROUND: A1c, a surrogate measure of glycemic control, is known to have a strong linear correlation with mean plasma glucose (MPG) when analyzed in populations of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20923490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND A1c, a surrogate measure of glycemic control, is known to have a strong linear correlation with mean plasma glucose (MPG) when analyzed in populations of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20923490", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 234, "text": "Hemoglobin A1c (HbA1c) has been used by clinicians as a means to measure short to intermediate term glucose control in diabetics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21920547", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 246, "text": "To estimate the impact of increased glycated hemoglobin (A1C) monitoring and treatment intensification for patients with type 2 diabetes (T2D) on quality measures and reimbursement within the Medicare Advantage Star (MA Star) program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28964455", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 105, "text": "Hemoglobin A1c (A1c) was recently added to the diagnostic criteria for diabetes and prediabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20861123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "AIMS: The purpose of this study was to develop a measure of psychosocial barriers to adherence in adolescents with type 1 diabetes (T1D) and examine relationships to patient characteristics, adherence, and hemoglobin A1C (A1C).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737172", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 334, "text": "To compare the ability of alternative wait time measures to predict glycated hemoglobin (A1C) levels among diabetes patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24511995", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 217, "text": "Chronic complications of diabetes can be reduced through optimal glycemic and lipid control as evaluated through measurement of glycosylated hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20807443", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 160, "text": " The assessment of glycemic control, most commonly using glycosylated hemoglobin (A1C), has been a major measure for care of patients with diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18030866", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 178, "text": "Glycated haemoglobin, as measured by haemoglobin A1C (A1C), c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21470266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Hemoglobin A1c is the measurement of glycated hemoglobin and can aid in both the diagnosis and continued management of diabetes mellitus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26630892", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 290, "text": "Diabetes treatment trials intended to seek indications for glycemic control are facilitated by the regulatory acceptance of glycosylated hemoglobin (A1C) as a validated intermediate efficacy end point", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027330", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 577, "text": "Hemoglobin A1c (HbA1c or simply A1c) is a measure of a long-term blood plasma glucose average, a reliable index to reflect one's diabetic condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15644138", "endSection": "abstract" } ] }, { "body": "Down's syndrome occurs when an individual has an extra copy or part of a copy of chromosome 21, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26391045", "http://www.ncbi.nlm.nih.gov/pubmed/19636252", "http://www.ncbi.nlm.nih.gov/pubmed/26243569", "http://www.ncbi.nlm.nih.gov/pubmed/9800738", "http://www.ncbi.nlm.nih.gov/pubmed/27245382", "http://www.ncbi.nlm.nih.gov/pubmed/2143053", "http://www.ncbi.nlm.nih.gov/pubmed/3036686", "http://www.ncbi.nlm.nih.gov/pubmed/9050924", "http://www.ncbi.nlm.nih.gov/pubmed/23394617", "http://www.ncbi.nlm.nih.gov/pubmed/18801168", "http://www.ncbi.nlm.nih.gov/pubmed/27931082", "http://www.ncbi.nlm.nih.gov/pubmed/11371509", "http://www.ncbi.nlm.nih.gov/pubmed/26300975", "http://www.ncbi.nlm.nih.gov/pubmed/18056702", "http://www.ncbi.nlm.nih.gov/pubmed/21081842", "http://www.ncbi.nlm.nih.gov/pubmed/19212162", "http://www.ncbi.nlm.nih.gov/pubmed/25862935", "http://www.ncbi.nlm.nih.gov/pubmed/24980541", "http://www.ncbi.nlm.nih.gov/pubmed/2880544", "http://www.ncbi.nlm.nih.gov/pubmed/15176487", "http://www.ncbi.nlm.nih.gov/pubmed/25706610", "http://www.ncbi.nlm.nih.gov/pubmed/25738006", "http://www.ncbi.nlm.nih.gov/pubmed/23686780", "http://www.ncbi.nlm.nih.gov/pubmed/28342823", "http://www.ncbi.nlm.nih.gov/pubmed/24210986", "http://www.ncbi.nlm.nih.gov/pubmed/7532356" ], "ideal_answer": [ "Yes, Downs syndrome is caused by a duplication or all or part of chromosome 21.", "Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21). ", "Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004314", "https://meshb.nlm.nih.gov/record/ui?ui=D056915", "https://meshb.nlm.nih.gov/record/ui?ui=D000076103", "https://meshb.nlm.nih.gov/record/ui?ui=D002891" ], "type": "yesno", "id": "5a76016683b0d9ea6600000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27931082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28342823", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 207, "text": "Down syndrome, or Trisomy 21, is the most frequently occurring chromosomal abnormality in live-born children. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27245382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Down syndrome (DS), caused by trisomy of chromosome 21,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26391045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Submicroscopic duplication of chromosome 21 and trisomy 21 phenotype (Down syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3036686", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Trisomy 21 or Down syndrome is a chromosomal disorder resulting from the presence of all or part of an extra Chromosome 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19636252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Down syndrome is a genetic disorder, occurring when an individual has all or part of an extra copy of chromosome 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19212162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Downs syndrome (DS) occurs due to an extra copy of chromosome 21.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25738006", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26243569", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 769, "text": "Aneuploidy refers to the presence of an extra copy of a specific chromosome, or trisomy, as seen in Down's syndrome (trisomy 21), or the absence of a single chromosome, or monosomy, as seen in Turner syndrome (a single X chromosome in females: 45, X).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Down syndrome (DS) or Trisomy 21 (Ts21) is caused by the presence of an extra copy of all or part of human chromosome 21 (Hsa21) and is the most frequent survivable congenital chromosomal abnormality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2143053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Down syndrome is usually caused by complete trisomy 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7532356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Down syndrome, the most frequent genetic disorder, is characterized by an extra copy of all or part of chromosome 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056702", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 190, "text": "Down syndrome (DS), caused by an extra copy of chromosome 21, affects 1 in 750 live births and is characterized by cognitive impairment and a constellation of congenital defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23394617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25706610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Down's syndrome results from the production of three copies of chromosome 21 within a cell. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9050924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Downs syndrome (DS) occurs due to an extra copy of chromosome 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25738006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Trisomy 21 (Ts21) is the most common live-born human aneuploidy; it results in a constellation of features known as Down's syndrome (DS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11371509", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 98, "text": "Down syndrome comprises multiple malformations and is due to trisomy of chromosome 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25862935", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 292, "text": "n 1959, J. Lejeune, M. Gautier, and R. Turpin demonstrated that the children with Down syndrome had an extra copy of chromosome 21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24210986", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 112, "text": "To develop a reliable and specific method for rapid prenatal diagnosis of Trisomy 21 (Down syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23686780", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 126, "text": "Trisomy 21 Down syndrome is the most common genetic cause for congenital malformations and intellectual disability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26300975", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 154, "text": "Down syndrome, characterized by an extra chromosome 21 is the most common genetic cause for congenital malformations and learning disability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801168", "endSection": "abstract" } ] }, { "body": "What is craniosynostosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17980312", "http://www.ncbi.nlm.nih.gov/pubmed/22939693", "http://www.ncbi.nlm.nih.gov/pubmed/27622416", "http://www.ncbi.nlm.nih.gov/pubmed/28060197", "http://www.ncbi.nlm.nih.gov/pubmed/22038757", "http://www.ncbi.nlm.nih.gov/pubmed/29093661", "http://www.ncbi.nlm.nih.gov/pubmed/26910679", "http://www.ncbi.nlm.nih.gov/pubmed/27226847", "http://www.ncbi.nlm.nih.gov/pubmed/24082921", "http://www.ncbi.nlm.nih.gov/pubmed/21811467", "http://www.ncbi.nlm.nih.gov/pubmed/18344207", "http://www.ncbi.nlm.nih.gov/pubmed/18326400", "http://www.ncbi.nlm.nih.gov/pubmed/27481450", "http://www.ncbi.nlm.nih.gov/pubmed/7884500", "http://www.ncbi.nlm.nih.gov/pubmed/14753738", "http://www.ncbi.nlm.nih.gov/pubmed/23249483", "http://www.ncbi.nlm.nih.gov/pubmed/20108486" ], "ideal_answer": [ "Craniosynostosis is a result of premature fusion of cranial sutures, leading to alterations of the pattern of cranial growth, resulting in abnormal shape of the head and dysmorphic facial features." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2340", "https://meshb.nlm.nih.gov/record/ui?ui=D003398" ], "type": "summary", "id": "5a77072c9e632bc06600000a", "snippets": [ { "offsetInBeginSection": 198, "offsetInEndSection": 354, "text": "Craniosynostosis has its origin in the failure of suture development between 2 bone centres or in early closure of the suture by bone centre tissue fusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18326400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Premature closure of cranial sutures (primary craniosynostosis) in children leads to characteristic skull deformities and prevents the constricted brain from growing normally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7884500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Craniosynostosis is a relatively common birth defect characterized by the premature fusion of one or more cranial sutures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Craniosynostosis represents a defection of the skull caused by early fusion of one or more cranial sutures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20108486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Craniosynostosis is the premature fusion of one or more sutures of the skull, which can be syndromic or isolated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22038757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Craniosynostosis is a complex condition, characterized by the premature fusion of one of more of the cranial sutures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22939693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Craniosynostosis, the premature closure of cranial suture, is a pathologic condition that affects 1/2000 live births", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21811467", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 134, "text": " Craniosynostosis is a congenital defect that causes one or more sutures on an infant's skull to close earlier than normal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24082921", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 113, "text": "Craniosynostosis is a condition that includes the premature fusion of one or multiple cranial sutures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26910679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Craniosynostosis is a defect of the skull caused by early fusion of one or more of the cranial sutures and affects 3 to 5 individuals per 10,000 live births.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Craniosynostosis is a birth defect characterized by premature fusion of one or more cranial sutures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18344207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Craniosynostosis, or premature fusion of the cranial sutures, occurs in approximately 1 in 2500 live births.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28060197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Craniosynostosis describes the premature fusion of one or more cranial sutures and can lead to dramatic manifestations in terms of appearance and functional impairment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23249483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Craniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29093661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Craniosynostosis is defined as the process of premature fusion of one or more of the cranial sutures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27622416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27226847", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "Craniosynostosis, premature fusion of the skull bones at the sutures, is the second most common human birth defect in the skull.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14753738", "endSection": "abstract" } ] }, { "body": "Which method has been developed for assignment of enhancers to target genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29070071" ], "ideal_answer": [ "While genomic assays can identify putative enhancers en masse, assigning target genes is a complex challenge. McEnhancer is a machine learning approach, which links target genes to putative enhancers via a semi-supervised learning algorithm that predicts gene expression patterns based on enriched sequence features. Predicted expression patterns were 73-98% accurate, predicted assignments showed strong Hi-C interaction enrichment, enhancer-associated histone modifications were evident, and known functional motifs were recovered." ], "exact_answer": [ "McEnhancer" ], "type": "factoid", "id": "5a6fa31ab750ff445500005e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "McEnhancer: predicting gene expression via semi-supervised assignment of enhancers to target genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29070071", "endSection": "title" }, { "offsetInBeginSection": 68, "offsetInEndSection": 752, "text": "While genomic assays can identify putative enhancers en masse, assigning target genes is a complex challenge. We devised a machine learning approach, McEnhancer, which links target genes to putative enhancers via a semi-supervised learning algorithm that predicts gene expression patterns based on enriched sequence features. Predicted expression patterns were 73-98% accurate, predicted assignments showed strong Hi-C interaction enrichment, enhancer-associated histone modifications were evident, and known functional motifs were recovered. Our model provides a general framework to link globally identified enhancers to targets and contributes to deciphering the regulatory genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29070071", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 393, "text": "We devised a machine learning approach, McEnhancer, which links target genes to putative enhancers via a semi-supervised learning algorithm that predicts gene expression patterns based on enriched sequence features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29070071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "McEnhancer: predicting gene expression via semi-supervised assignment of enhancers to target genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29070071", "endSection": "title" } ] }, { "body": "Describe Click-PEGylation", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28366801" ], "ideal_answer": [ "One approach that can facilitate a targeted assessment of candidate proteins, as well as proteins that are low in abundance or proteomically challenging, is by electrophoretic mobility shift assays. Redox-modified cysteine residues are selectively tagged with a large group, such as a polyethylene glycol (PEG) polymer, and then the proteins are separated by electrophoresis followed by immunoblotting, which allows the inference of redox changes based on band shifts. However, the applicability of this method has been impaired by the difficulty of cleanly modifying protein thiols by large PEG reagents. To establish a more robust method for redox-selective PEGylation a Click chemistry approach has been developed where free thiol groups are first labelled with a reagent modified to contain an alkyne moiety, which is subsequently Click-reacted with a PEG molecule containing a complementary azide function. This strategy can be adapted to study reversibly reduced or oxidised cysteines. Separation of the thiol labelling step from the PEG conjugation greatly facilitates the fidelity and flexibility of this approach." ], "concepts": [ "http://www.biosemantics.org/jochem#4264214", "https://meshb.nlm.nih.gov/record/ui?ui=D057930", "http://amigo.geneontology.org/amigo/term/GO:0051776", "http://amigo.geneontology.org/amigo/term/GO:0071461", "http://amigo.geneontology.org/amigo/term/GO:0051775" ], "type": "summary", "id": "5a6fa9f7b750ff4455000061", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Click-PEGylation - A mobility shift approach to assess the redox state of cysteines in candidate proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366801", "endSection": "title" }, { "offsetInBeginSection": 945, "offsetInEndSection": 2171, "text": "One approach that can facilitate a targeted assessment of candidate proteins, as well as proteins that are low in abundance or proteomically challenging, is by electrophoretic mobility shift assays. Redox-modified cysteine residues are selectively tagged with a large group, such as a polyethylene glycol (PEG) polymer, and then the proteins are separated by electrophoresis followed by immunoblotting, which allows the inference of redox changes based on band shifts. However, the applicability of this method has been impaired by the difficulty of cleanly modifying protein thiols by large PEG reagents. To establish a more robust method for redox-selective PEGylation, we have utilised a Click chemistry approach, where free thiol groups are first labelled with a reagent modified to contain an alkyne moiety, which is subsequently Click-reacted with a PEG molecule containing a complementary azide function. This strategy can be adapted to study reversibly reduced or oxidised cysteines. Separation of the thiol labelling step from the PEG conjugation greatly facilitates the fidelity and flexibility of this approach. Here we show how the Click-PEGylation technique can be used to interrogate the redox state of proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366801", "endSection": "abstract" }, { "offsetInBeginSection": 2068, "offsetInEndSection": 2175, "text": "Here we show how the Click-PEGylation technique can be used to interrogate the redox state of proteins.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366801", "endSection": "abstract" }, { "offsetInBeginSection": 2068, "offsetInEndSection": 2171, "text": "Here we show how the Click-PEGylation technique can be used to interrogate the redox state of proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Click-PEGylation - A mobility shift approach to assess the redox state of cysteines in candidate proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366801", "endSection": "title" }, { "offsetInBeginSection": 2068, "offsetInEndSection": 2172, "text": "Here we show how the Click-PEGylation technique can be used to interrogate the redox state of proteins..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366801", "endSection": "abstract" } ] }, { "body": "A SLEDAI score is associated with Systemic Lupus Erythematosus. What is a SLEDAI score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22516994", "http://www.ncbi.nlm.nih.gov/pubmed/27795838", "http://www.ncbi.nlm.nih.gov/pubmed/23172751", "http://www.ncbi.nlm.nih.gov/pubmed/17477466", "http://www.ncbi.nlm.nih.gov/pubmed/28116652", "http://www.ncbi.nlm.nih.gov/pubmed/28123902", "http://www.ncbi.nlm.nih.gov/pubmed/25861457", "http://www.ncbi.nlm.nih.gov/pubmed/10685800", "http://www.ncbi.nlm.nih.gov/pubmed/16761499", "http://www.ncbi.nlm.nih.gov/pubmed/10955328", "http://www.ncbi.nlm.nih.gov/pubmed/19762400", "http://www.ncbi.nlm.nih.gov/pubmed/11480850", "http://www.ncbi.nlm.nih.gov/pubmed/15468356", "http://www.ncbi.nlm.nih.gov/pubmed/8235662", "http://www.ncbi.nlm.nih.gov/pubmed/27365721", "http://www.ncbi.nlm.nih.gov/pubmed/2195948", "http://www.ncbi.nlm.nih.gov/pubmed/16681575", "http://www.ncbi.nlm.nih.gov/pubmed/12007552", "http://www.ncbi.nlm.nih.gov/pubmed/28243944", "http://www.ncbi.nlm.nih.gov/pubmed/16354890", "http://www.ncbi.nlm.nih.gov/pubmed/16150398", "http://www.ncbi.nlm.nih.gov/pubmed/12945718", "http://www.ncbi.nlm.nih.gov/pubmed/24705033", "http://www.ncbi.nlm.nih.gov/pubmed/7993706" ], "triples": [ { "p": "http://data.linkedct.org/resource/linkedct/measure", "s": "http://data.linkedct.org/resource/primary_outcomes/53520", "o": "SLEDAI" }, { "p": "http://data.linkedct.org/resource/linkedct/measure", "s": "http://data.linkedct.org/resource/primary_outcomes/37202", "o": "SLEDAI" }, { "p": "http://data.linkedct.org/resource/linkedct/measure", "s": "http://data.linkedct.org/resource/primary_outcomes/22207", "o": "SLEDAI" } ], "ideal_answer": [ "Disease activity of Systemic Lupus Erythematosis was evaluated according to the SLE Disease Activity Index (SLEDAI) score which score disease activity based on a number of parameters.", "A complete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was obtained for each patient.", "Disease activity of SLE was evaluated according to the SLE Disease Activity Index (SLEDAI) score." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:8857", "http://www.disease-ontology.org/api/metadata/DOID:9074", "https://meshb.nlm.nih.gov/record/ui?ui=D008180" ], "type": "summary", "id": "5a897601fcd1d6a10c000008", "snippets": [ { "offsetInBeginSection": 429, "offsetInEndSection": 526, "text": "Disease activity of SLE was evaluated according to the SLE Disease Activity Index (SLEDAI) score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28123902", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 344, "text": "SLE patients were examined to evaluate their clinical status and disease activity. A complete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was obtained for each patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The course and prognostic value of disease activity measured by the validated Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was investigated in 68 newly diagnosed black Caribbean cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8235662", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "The objective of this study is to determine if digital vasculitis (DV), a clinical manifestation with a high systemic lupus erythematosus disease activity index (SLEDAI) score, is associated with lupus severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19762400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "OBJECTIVE To determine whether Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores correlate with the clinician's impression of level of disease activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10685800", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 539, "text": "Sociodemographic, disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), therapy and laboratory variables were evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11480850", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 453, "text": "Systemic lupus erythematosus disease activity index (SLEDAI), C3, C4 and anti-double stranded DNA levels were estimated and repeated monthly till remission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27365721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the most commonly used measure of disease activity for children with systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12945718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "To determine whether Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores correlate with the clinician's impression of level of disease activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10685800", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 694, "text": " SLE Disease Activity Index (SLEDAI) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25861457", "endSection": "abstract" }, { "offsetInBeginSection": 57, "offsetInEndSection": 117, "text": "Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15468356", "endSection": "title" }, { "offsetInBeginSection": 617, "offsetInEndSection": 660, "text": "SLE Disease Activity Index (SLEDAI) scores,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10955328", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 373, "text": "systemic lupus erythematosus Disease Activity Index (SLEDAI)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27795838", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 318, "text": "SLE Disease Activity Index (SLEDAI) score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16681575", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 650, "text": "[SLE disease activity index (SLEDAI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28243944", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 456, "text": "systematic lupus erythematosus disease activity index (SLEDAI) score", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22516994", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 521, "text": "Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16354890", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 127, "text": "Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12007552", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1033, "text": "systemic lupus erythematosus disease activity index (SLEDAI) scoring system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705033", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 625, "text": "Clinical disease activity was quantified by the SLE Disease Activity Index (SLEDAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16761499", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 311, "text": "SLEDAI (Systemic Lupus Erythematosus Disease Activity Index)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7993706", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 630, "text": "SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2195948", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 707, "text": " the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16150398", "endSection": "abstract" } ] }, { "body": "What disease is the ALK tyrosine kinase associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28007627", "http://www.ncbi.nlm.nih.gov/pubmed/25870797", "http://www.ncbi.nlm.nih.gov/pubmed/27836576", "http://www.ncbi.nlm.nih.gov/pubmed/21213368", "http://www.ncbi.nlm.nih.gov/pubmed/26503946", "http://www.ncbi.nlm.nih.gov/pubmed/27179218", "http://www.ncbi.nlm.nih.gov/pubmed/27468968", "http://www.ncbi.nlm.nih.gov/pubmed/22084642", "http://www.ncbi.nlm.nih.gov/pubmed/11561161", "http://www.ncbi.nlm.nih.gov/pubmed/25407901", "http://www.ncbi.nlm.nih.gov/pubmed/27573755", "http://www.ncbi.nlm.nih.gov/pubmed/26811689", "http://www.ncbi.nlm.nih.gov/pubmed/25727400", "http://www.ncbi.nlm.nih.gov/pubmed/27892978", "http://www.ncbi.nlm.nih.gov/pubmed/21613408", "http://www.ncbi.nlm.nih.gov/pubmed/22184391", "http://www.ncbi.nlm.nih.gov/pubmed/23104988", "http://www.ncbi.nlm.nih.gov/pubmed/22681779", "http://www.ncbi.nlm.nih.gov/pubmed/21205076", "http://www.ncbi.nlm.nih.gov/pubmed/26395848", "http://www.ncbi.nlm.nih.gov/pubmed/21829174", "http://www.ncbi.nlm.nih.gov/pubmed/18923525", "http://www.ncbi.nlm.nih.gov/pubmed/20961208", "http://www.ncbi.nlm.nih.gov/pubmed/25351247", "http://www.ncbi.nlm.nih.gov/pubmed/17611412", "http://www.ncbi.nlm.nih.gov/pubmed/18070884", "http://www.ncbi.nlm.nih.gov/pubmed/27217763", "http://www.ncbi.nlm.nih.gov/pubmed/26294238", "http://www.ncbi.nlm.nih.gov/pubmed/27899405", "http://www.ncbi.nlm.nih.gov/pubmed/20979469", "http://www.ncbi.nlm.nih.gov/pubmed/25979929", "http://www.ncbi.nlm.nih.gov/pubmed/23499906", "http://www.ncbi.nlm.nih.gov/pubmed/25759656", "http://www.ncbi.nlm.nih.gov/pubmed/27646667", "http://www.ncbi.nlm.nih.gov/pubmed/25601484", "http://www.ncbi.nlm.nih.gov/pubmed/26076736", "http://www.ncbi.nlm.nih.gov/pubmed/21288922", "http://www.ncbi.nlm.nih.gov/pubmed/22998583" ], "ideal_answer": [ "The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas" ], "exact_answer": [ "cancer" ], "type": "factoid", "id": "5a871a6861bb38fb24000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "ALK positive anaplastic large cell lymphoma is a T-cell lymphoma usually occurring in children and young adults. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27468968", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 358, "text": " A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0\u00a0lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27646667", "endSection": "abstract" }, { "offsetInBeginSection": 2108, "offsetInEndSection": 2272, "text": "Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27892978", "endSection": "abstract" }, { "offsetInBeginSection": 50, "offsetInEndSection": 160, "text": "investigational ALK inhibitor brigatinib is active in patients with ALK-rearranged non-small cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899405", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 589, "text": "Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, initially identified through the analysis of a specific translocation associated with a rare subtype of non-Hodgkin's lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21205076", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 696, "text": "Recently it was demonstrated that ALK is frequently mutated in sporadic cases with advanced neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21205076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Anaplastic lymphoma kinase (ALK) is an important molecular target in neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25351247", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 340, "text": "Although tyrosine kinase inhibitors abrogating ALK activity are currently in clinical use for the treatment of ALK-positive (ALK(+)) disease, monotherapy with ALK tyrosine kinase inhibitors may not be an adequate solution for ALK(+) neuroblastoma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25351247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21613408", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 390, "text": "We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20979469", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1073, "text": "The ALK gene is silent in adult tissues except for restricted sites within the nervous system (consequently, patients with ALK-positive lymphoma produce antibodies to the ALK protein) but is expressed in some neuroblastomas and rhabdomyosarcomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11561161", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "BACKGROUND The translocations of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene on chromosome 2p have been identified in non-small-cell lung cancers (NSCLCs) as oncogenic driver mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25407901", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 439, "text": "SUMMARY The ALK protein functions as a transmembrane receptor tyrosine kinase; rearrangements of the ALK gene are associated with the development of NSCLC with adenocarcinoma histology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26294238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Anaplastic lymphoma kinase (ALK) rearrangement lung cancer responds to ALK tyrosine kinase inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26811689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "INTRODUCTION Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, has been initially identified through its involvement in chromosomal translocations associated with anaplastic large cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22998583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Patients with non-small cell lung cancer (NSCLC) who harbor anaplastic lymphoma kinase (ALK) gene rearrangements can derive significant clinical benefit from ALK tyrosine kinase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25870797", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1273, "text": "Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573755", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 393, "text": "This review summarises the latest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients with cancer that is ALK-positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573755", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 453, "text": "Genetic rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) gene occur in non-small cell lung cancer (NSCLC), anaplastic large cell lymphomoas, inflammatory myofibroblastic tumors, and other cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22084642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "INTRODUCTION: NSCLC with de novo anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements and EGFR or KRAS mutations co-occur very rarely.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "ALK (anaplastic lymphoma kinase) is a transmembrane receptor tyrosine kinase, initially discovered as part of the NPM-ALK fusion protein, resulting from a chromosomal rearrangement frequently associated with anaplastic large cell lymphomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17611412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is sensitive to treatment with an ALK-tyrosine kinase inhibitor (-TKI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26395848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase was initially discovered as a component of the fusion protein nucleophosmin (NPM)-ALK in anaplastic large-cell lymphoma (ALCL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25979929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor involved in both solid and hematological tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25727400", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 282, "text": "patients with ALK-positive non-small-cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25759656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Rearrangements of the anaplastic lymphoma kinase (ALK) gene originally discovered nearly 20 years ago in the context of anaplastic large cell lymphoma were identified as oncogenic drivers in a subset of non-small cell lung cancers (NSCLCs) in 2007.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26076736", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 408, "text": "The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a population of NSCLCs in whom dysregulation of ALK-tyrosine kinase (-TK) leads to uncontrolled proliferation of cancer cells,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25601484", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 476, "text": "ALK has been identified as a major neuroblastoma predisposition gene and activating mutations have been identified in a subset of sporadic neuroblastoma tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23499906", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 448, "text": "Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18923525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%-8% of non-small-cell lung cancer (NSCLC) patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27217763", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 207, "text": "Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma defined by the presence of chromosomal translocations involving the ALK tyrosine kinase gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22681779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "Renal Medullary Carcinoma (RMC) is an aggressive malignancy that affects young black individuals with sickle cell trait. No effective treatment is available, resulting in an ominous clinical course, with overall survival averaging less than four months. We report rearrangement of the ALK receptor tyrosine kinase in a pediatric case of RMC harboring a t(2;10)(p23;q22) translocation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21213368", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 457, "text": " Aberrant ALK activity has been implicated in the oncogenesis of human cancers as a fusion protein in anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, diffuse large B-cell lymphoma, systemic histiocytosis and NSCLC or through mutations in the full length protein in hereditary familial neuroblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20961208", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 568, "text": "Chromosomal rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) occur in a variety of human malignancies including non-small cell lung cancer (NSCLC), anaplastic large cell lymphomas, and inflammatory myofibroblastic tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21288922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 350, "text": "NPM/ALK is an oncogenic fusion protein expressed in approximately 50% of anaplastic large cell lymphoma cases. It derives from the t(2;5)(p23;q35) chromosomal translocation that fuses the catalytic domain of the tyrosine kinase, anaplastic lymphoma kinase (ALK), with the dimerization domain of the ubiquitously expressed nucleophosmin (NPM) protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18070884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Rearrangements involving the ALK gene were identified in a variety of cancers,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27179218", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 316, "text": "genetic alterations are mutations in the kinase domain of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23104988", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 225, "text": " The aim of this study is to investigate anaplastic lymphoma kinase (ALK) protein expression and underlying genetic aberrations in rhabdomyosarcoma (RMS), with special attention to clinical and prognostic implications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22184391", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 191, "text": "Anaplastic lymphoma receptor tyrosine kinase gene (ALK) fusion is a distinct molecular subclassification of NSCLC that is targeted by anaplastic lymphoma kinase (ALK) inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27836576", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 295, "text": "The discovery of translocations involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase in a subset of non-small cell lung cancers has become a paradigm for precision medicine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26503946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is involved in the pathogenesis of different types of human cancers, including neuroblastoma (NB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21829174", "endSection": "abstract" } ] }, { "body": "CURB65 score is used for stratification of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26874956", "http://www.ncbi.nlm.nih.gov/pubmed/20920140", "http://www.ncbi.nlm.nih.gov/pubmed/16928720", "http://www.ncbi.nlm.nih.gov/pubmed/29161297", "http://www.ncbi.nlm.nih.gov/pubmed/21539743", "http://www.ncbi.nlm.nih.gov/pubmed/24931899", "http://www.ncbi.nlm.nih.gov/pubmed/28681972", "http://www.ncbi.nlm.nih.gov/pubmed/28678546", "http://www.ncbi.nlm.nih.gov/pubmed/26237261" ], "ideal_answer": [ "CURB65 (confusion, urea, respiration, blood pressure; age>65\u2009years) is used for assessment of pneumonia severity." ], "exact_answer": [ "pneumonia" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004194" ], "type": "factoid", "id": "5a67ab79b750ff445500000b", "snippets": [ { "offsetInBeginSection": 1312, "offsetInEndSection": 1503, "text": "Severity assessment tools (e.g. CURB65) that are used to guide early management decisions in CAP have not been widely validated in low-income settings and locally adapted tools are required. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28681972", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 635, "text": "Scores for the pneumonia severity index (PSI); CURB65 (confusion, urea, respiration, blood pressure; age>65\u2009years); Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) guidelines for severe CAP; Acute Physiology, Chronic Health Evaluation (APACHE) II; Sequential Organ Failure Assessment (SOFA); and quick SOFA (qSOFA) were calculated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28678546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Prognostic performance of MR-pro-adrenomedullin in patients with community acquired pneumonia in the Emergency Department compared to clinical severity scores PSI and CURB.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29161297", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "AIM: (i) evaluate the performance of MR-pro-ADM in reflecting the outcome and risk for CAP patients in the emergency department, and (ii) compare the prognostic performance of MR-pro-ADM with that of clinical scores PSI and CURB65.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29161297", "endSection": "abstract" }, { "offsetInBeginSection": 2673, "offsetInEndSection": 2931, "text": "CONCLUSIONS: The present study confirms that assessment of MR-pro-ADM levels in CAP patients in addition to CURB scores increases the prognostic accuracy of CURB alone and may help rule out discrepancies arising from flawed clinical severity classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29161297", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 536, "text": "The cytokine response during pneumonia is different in bacterial vs viral infections; some of these cytokines correlate with clinical severity scales such as CURB65 or SOFA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26874956", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 325, "text": "The CURB65 score was developed to predict mortality risk in community acquired pneumonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20920140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The CURB65 pneumonia severity score outperforms generic sepsis and early warning scores in predicting mortality in community-acquired pneumonia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16928720", "endSection": "title" }, { "offsetInBeginSection": 1593, "offsetInEndSection": 1682, "text": "CURB65 should not be supplanted by SIRS or SEWS for initial prognostic assessment in CAP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16928720", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 317, "text": "The CURB65 score was developed to predict mortality risk in community acquired pneumonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20920140", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 318, "text": "We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21539743", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 767, "text": "RESULTS CURB65 and ProADM predicted both adverse events and mortality similarly well in CAP and non-CAP-LRTI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21539743", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 936, "text": "The combined CURB65-A risk score provided better prediction of death and adverse events than the CURB65 score in the entire cohort and in CAP and non-CAP-LRTI patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21539743", "endSection": "abstract" }, { "offsetInBeginSection": 1704, "offsetInEndSection": 1904, "text": "CONCLUSION Presepsin is a valuable biomarker in predicting severity and outcome in CAP patients in the ED and Presepsin in combination with CURB65 score significantly enhanced the predictive accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "BACKGROUND An intervention trial found a trend for shorter length of stay (LOS) in patients with community-acquired pneumonia (CAP) when the CURB65 score was combined with the prognostic biomarker proadrenomedullin (ProADM) (CURB65-A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26237261", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 793, "text": "A composite score (CURB65-A) was created combining CURB65 classes with ProADM cut-offs to further risk-stratify patients.
RESULTS: CURB65 and ProADM predicted both adverse events and mortality similarly well in CAP and non-CAP-LRTI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21539743", "endSection": "abstract" } ] }, { "body": "Which resource has been developed in order to study the transcriptional regulation of GABAergic cell fate?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27710791" ], "ideal_answer": [ "Subpallial Enhancer Transgenic Lines is a data and tool resource to study transcriptional regulation of GABAergic cell fate." ], "exact_answer": [ "Subpallial Enhancer Transgenic Lines" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D050436" ], "type": "factoid", "id": "5a6d196db750ff4455000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Subpallial Enhancer Transgenic Lines: a Data and Tool Resource to Study Transcriptional Regulation of GABAergic Cell Fate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27710791", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1029, "text": "Elucidating the transcriptional circuitry controlling forebrain development requires an understanding of\u00a0enhancer activity and regulation. We generated stable transgenic mouse lines that express CreERT2and GFP from ten different enhancer elements with activity in distinct domains within the embryonic basal ganglia. We used these unique tools to generate a comprehensive regional fate map of the mouse subpallium, including sources for specific subtypes of amygdala neurons. We then focused on deciphering transcriptional mechanisms that control enhancer activity. Using machine-learning computations, in\u00a0vivo chromosomal occupancy of 13 transcription factors that regulate subpallial patterning and differentiation and analysis of enhancer activity in Dlx1/2 and Lhx6 mutants, we elucidated novel molecular mechanisms that regulate region-specific enhancer activity in the developing brain. Thus, these subpallial enhancer transgenic lines are data and tool\u00a0resources to study transcriptional regulation of GABAergic cell fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27710791", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1028, "text": "Thus, these subpallial enhancer transgenic lines are data and tool\u00a0resources to study transcriptional regulation of GABAergic cell fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27710791", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1033, "text": "Thus, these subpallial enhancer transgenic lines are data and tool\u00a0resources to study transcriptional regulation of GABAergic cell fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27710791", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Subpallial Enhancer Transgenic Lines: a Data and Tool Resource to Study Transcriptional Regulation of GABAergic Cell Fate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27710791", "endSection": "title" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1031, "text": "Thus, these subpallial enhancer transgenic lines are data and tool\u00a0resources to study transcriptional regulation of GABAergic cell fate..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27710791", "endSection": "abstract" } ] }, { "body": "Is creatinine assessment included in the MELD score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27480755", "http://www.ncbi.nlm.nih.gov/pubmed/28856226", "http://www.ncbi.nlm.nih.gov/pubmed/27779785", "http://www.ncbi.nlm.nih.gov/pubmed/28510807", "http://www.ncbi.nlm.nih.gov/pubmed/29055930", "http://www.ncbi.nlm.nih.gov/pubmed/23293714", "http://www.ncbi.nlm.nih.gov/pubmed/27842889", "http://www.ncbi.nlm.nih.gov/pubmed/22178107", "http://www.ncbi.nlm.nih.gov/pubmed/15482344", "http://www.ncbi.nlm.nih.gov/pubmed/28198820", "http://www.ncbi.nlm.nih.gov/pubmed/29171941", "http://www.ncbi.nlm.nih.gov/pubmed/23403770" ], "ideal_answer": [ "Yes, creatinine is included in the Model For End-Stage Liver Disease (MELD) score. Other components of the MELD score are international normalized ratio and serum billirubin. The MELD score is used for evaluation of liver cirrhosis." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4273958", "https://meshb.nlm.nih.gov/record/ui?ui=D003404" ], "type": "yesno", "id": "5a68f633b750ff4455000019", "snippets": [ { "offsetInBeginSection": 877, "offsetInEndSection": 1001, "text": "Model For End-Stage Liver Disease (MELD) scores were calculated as 3.78\u00d7ln[TB]\u00a0+\u00a011.2\u00d7ln[INR]\u00a0+\u00a09.57\u00d7ln[creatinine]\u00a0+\u00a06.43. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27842889", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1062, "text": "A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27779785", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1050, "text": "Among patients with MELD score>35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28198820", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 493, "text": "Patient risk factors evaluated include age, INR (international normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage Liver Disease). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28510807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Limited comparability of creatinine assays in patients with liver cirrhosis and their impact on the MELD score.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28856226", "endSection": "title" }, { "offsetInBeginSection": 141, "offsetInEndSection": 310, "text": "The model of end-stage liver disease (MELD) score is used for this purpose in most countries and incorporates bilirubin, International Normalized ratio, and creatinine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28856226", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 707, "text": "The MELD score was calculated using international normalized ratio, serum billirubin and creatinine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29055930", "endSection": "abstract" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1562, "text": "Regression analysis identified high creatinine and INR, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22178107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "OBJECTIVES: The model for end-stage liver disease score (MELD = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 11.2*[PT-INR] + 6.4) predicts mortality for tricuspid valve surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23403770", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 805, "text": "Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.
METHODS: A total of 172 patients (male: 66, female: 106; mean age, 63.8 \u00b1 10.3 years) who underwent tricuspid replacement (n = 18) or repair (n = 154) from January 1991 to July 2011 at a single centre were included.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23403770", "endSection": "abstract" }, { "offsetInBeginSection": 3159, "offsetInEndSection": 3356, "text": "CONCLUSION Incorporating eGFR obtained by the 6-variable MDRD equation into the MELD score showed an equal predictive performance in in-hospital mortality compared to a creatinine-based MELD score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23293714", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 560, "text": "Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23403770", "endSection": "abstract" } ] }, { "body": "List the two most important synaptic markers.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28264928", "http://www.ncbi.nlm.nih.gov/pubmed/28438613", "http://www.ncbi.nlm.nih.gov/pubmed/28269788", "http://www.ncbi.nlm.nih.gov/pubmed/28933272", "http://www.ncbi.nlm.nih.gov/pubmed/27422357", "http://www.ncbi.nlm.nih.gov/pubmed/28987163", "http://www.ncbi.nlm.nih.gov/pubmed/28205585" ], "ideal_answer": [ "postsynaptic density 95\nsynaptophysin", "Synaptic markers include acetylcholine, gamma-aminobutyric acid (GABA), glutamine, glycine and synaptophysin." ], "exact_answer": [ [ "postsynaptic density 95", "PSD-95" ], [ "synaptophysin", "SVP" ] ], "type": "list", "id": "5a8861eb8cb19eca6b000001", "snippets": [ { "offsetInBeginSection": 675, "offsetInEndSection": 856, "text": "hese improvements in neuron viability and function were correlated with significant increases in the levels of post-synaptic marker PSD95 and the pre-synaptic marker synaptophysin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28205585", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 823, "text": "post-synaptic density (PSD)-95 protein, a post-synaptic marker", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28264928", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 888, "text": "Hippocampal levels of synaptic marker postsynaptic density 95 (PSD-95) and synaptophysin (SVP) were measured using western blot analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28269788", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1376, "text": "These animals showed a significant loss of presynaptic markers (synaptophysin; p<0.001),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28438613", "endSection": "abstract" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1233, "text": "increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27422357", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 794, "text": "The most widely used neuronal markers comprise phosphorylated and nonphosphorylated neurofilaments, microtubule-associated protein-2, NeuN, or synaptic markers such as synaptophysin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28987163", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1132, "text": "Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28933272", "endSection": "abstract" } ] }, { "body": "What is a SERM?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26704594", "http://www.ncbi.nlm.nih.gov/pubmed/28372959", "http://www.ncbi.nlm.nih.gov/pubmed/15500393", "http://www.ncbi.nlm.nih.gov/pubmed/28131133", "http://www.ncbi.nlm.nih.gov/pubmed/16951470", "http://www.ncbi.nlm.nih.gov/pubmed/10819845", "http://www.ncbi.nlm.nih.gov/pubmed/24373794", "http://www.ncbi.nlm.nih.gov/pubmed/24930824", "http://www.ncbi.nlm.nih.gov/pubmed/18824103", "http://www.ncbi.nlm.nih.gov/pubmed/16451049", "http://www.ncbi.nlm.nih.gov/pubmed/16081843", "http://www.ncbi.nlm.nih.gov/pubmed/28978566", "http://www.ncbi.nlm.nih.gov/pubmed/28978567", "http://www.ncbi.nlm.nih.gov/pubmed/25466304", "http://www.ncbi.nlm.nih.gov/pubmed/14505351", "http://www.ncbi.nlm.nih.gov/pubmed/27240168", "http://www.ncbi.nlm.nih.gov/pubmed/16951478", "http://www.ncbi.nlm.nih.gov/pubmed/16972673", "http://www.ncbi.nlm.nih.gov/pubmed/27048997", "http://www.ncbi.nlm.nih.gov/pubmed/23925896", "http://www.ncbi.nlm.nih.gov/pubmed/15864926", "http://www.ncbi.nlm.nih.gov/pubmed/14645673", "http://www.ncbi.nlm.nih.gov/pubmed/20169039", "http://www.ncbi.nlm.nih.gov/pubmed/25236805", "http://www.ncbi.nlm.nih.gov/pubmed/28185712", "http://www.ncbi.nlm.nih.gov/pubmed/12036407", "http://www.ncbi.nlm.nih.gov/pubmed/19382614", "http://www.ncbi.nlm.nih.gov/pubmed/20303261", "http://www.ncbi.nlm.nih.gov/pubmed/11795362", "http://www.ncbi.nlm.nih.gov/pubmed/12650712", "http://www.ncbi.nlm.nih.gov/pubmed/18279543", "http://www.ncbi.nlm.nih.gov/pubmed/11046073", "http://www.ncbi.nlm.nih.gov/pubmed/10629380", "http://www.ncbi.nlm.nih.gov/pubmed/22570330", "http://www.ncbi.nlm.nih.gov/pubmed/28098599", "http://www.ncbi.nlm.nih.gov/pubmed/20485909", "http://www.ncbi.nlm.nih.gov/pubmed/27585851", "http://www.ncbi.nlm.nih.gov/pubmed/28030966", "http://www.ncbi.nlm.nih.gov/pubmed/24410282", "http://www.ncbi.nlm.nih.gov/pubmed/11421557", "http://www.ncbi.nlm.nih.gov/pubmed/12373918", "http://www.ncbi.nlm.nih.gov/pubmed/18044180", "http://www.ncbi.nlm.nih.gov/pubmed/17504144", "http://www.ncbi.nlm.nih.gov/pubmed/10769110", "http://www.ncbi.nlm.nih.gov/pubmed/26343247", "http://www.ncbi.nlm.nih.gov/pubmed/20446043", "http://www.ncbi.nlm.nih.gov/pubmed/23062036", "http://www.ncbi.nlm.nih.gov/pubmed/17448265", "http://www.ncbi.nlm.nih.gov/pubmed/16263696", "http://www.ncbi.nlm.nih.gov/pubmed/18637493", "http://www.ncbi.nlm.nih.gov/pubmed/24667357" ], "ideal_answer": [ "A SERM is a Selective Estrogen Receptor Modulator.", "selective estrogen receptor modulator (SERM),", "elective estrogen receptor modulator (SERM),", "elective estrogen receptor modulator (SERM),. " ], "exact_answer": [ "Selective Estrogen Receptor Modulator" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D020845", "https://meshb.nlm.nih.gov/record/ui?ui=D020847" ], "type": "factoid", "id": "5a74e9ad0384be955100000a", "snippets": [ { "offsetInBeginSection": 26, "offsetInEndSection": 70, "text": "elective estrogen receptor modulator (SERM),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27585851", "endSection": "abstract" }, { "offsetInBeginSection": 42, "offsetInEndSection": 88, "text": "selective estrogen receptor modulators (SERMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28098599", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 915, "text": "selective estrogen receptor modulators (SERM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28030966", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 116, "text": "selective estrogen receptor modulator (SERM),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28131133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Selective estrogen receptor modulators (SERMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20485909", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 274, "text": "he selective ER modulators (SERMs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Selective estrogen receptor modulators (SERMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24373794", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 65, "text": "selective estrogen receptor modulators (SERMs)", "beginSection": "abstract", "document": 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"offsetInBeginSection": 171, "offsetInEndSection": 216, "text": "elective estrogen receptor modulators (SERMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19382614", "endSection": "abstract" }, { "offsetInBeginSection": 67, "offsetInEndSection": 102, "text": "estrogen receptor modulator (SERM) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26704594", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 281, "text": "selective estrogen receptor modulators (SERMs) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18637493", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 116, "text": "selective estrogen receptor modulator (SERM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27240168", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 152, "text": "selective estrogen receptor modulator (SERM) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14505351", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 383, "text": "Selective estrogen receptor modulators (SERMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11046073", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 49, "text": " SERMs (selective estrogen receptor modulators", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10769110", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 445, "text": "elective estrogen receptor modulator (SERM) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18044180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "A selective estrogen receptor modulator (SERM) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16451049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Selective estrogen receptor modulators (SERMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23062036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Selective estrogen receptor modulators (SERMs) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17448265", "endSection": "abstract" } ] }, { "body": "Is celiac disease caused by gliadin-induced transglutaminase-2 (TG2)-dependent events ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18793760", "http://www.ncbi.nlm.nih.gov/pubmed/26883352", "http://www.ncbi.nlm.nih.gov/pubmed/14747475", "http://www.ncbi.nlm.nih.gov/pubmed/20300628", "http://www.ncbi.nlm.nih.gov/pubmed/27613408", "http://www.ncbi.nlm.nih.gov/pubmed/27130174" ], "ideal_answer": [ "Celiac disease is caused by gliadin-induced transglutaminase-2 (TG2)-dependent events following ingestion of dietary gluten." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D002446", "http://www.disease-ontology.org/api/metadata/DOID:10608" ], "type": "yesno", "id": "5a79d195faa1ab7d2e00000e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26883352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Celiac disease (CD) is an autoimmune enteropathy initiated and sustained by the ingestion of gluten in genetically susceptible individuals. It is caused by a dysregulated immune response toward both dietary antigens, the gluten proteins of wheat, rye, and barley, and autoantigens, the enzyme tissue transglutaminase (TG2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27130174", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20300628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Transglutaminase 2 (TG2) catalyzes cross-linking or deamidation of glutamine residues in peptides and proteins. The in vivo deamidation of gliadin peptides plays an important role in the immunopathogenesis of celiac disease (CD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18793760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Tissue transglutaminase (TG2) modifies proteins and peptides by transamidation or deamidation of specific glutamine residues. TG2 also has a central role in the pathogenesis of celiac disease. The enzyme is both the target of disease-specific autoantibodies and generates deamidated gliadin peptides recognized by intestinal T cells from patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14747475", "endSection": "abstract" } ] }, { "body": "Which resource contains accurate enhancer predictions in the developing limb?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28827824" ], "ideal_answer": [ "Limb-Enhancer Genie (LEG) is a collection of highly accurate, genome-wide predictions of enhancers in the developing limb, available through a user-friendly online interface. Limb enhancers are predicted using a combination of >50 published limb-specific datasets and clusters of evolutionarily conserved transcription factor binding sites, taking advantage of the patterns observed at previously in vivo validated elements." ], "exact_answer": [ "Limb-Enhancer Genie (LEG)" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004742", "http://amigo.geneontology.org/amigo/term/GO:0060173", "http://amigo.geneontology.org/amigo/term/GO:0060174" ], "type": "factoid", "id": "5a6d1733b750ff4455000030", "snippets": [ { "offsetInBeginSection": 415, "offsetInEndSection": 853, "text": "Here we present the Limb-Enhancer Genie (LEG), a collection of highly accurate, genome-wide predictions of enhancers in the developing limb, available through a user-friendly online interface. We predict limb enhancers using a combination of>50 published limb-specific datasets and clusters of evolutionarily conserved transcription factor binding sites, taking advantage of the patterns observed at previously in vivo validated elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28827824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Limb-Enhancer Genie: An accessible resource of accurate enhancer predictions in the developing limb.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28827824", "endSection": "title" }, { "offsetInBeginSection": 415, "offsetInEndSection": 607, "text": "Here we present the Limb-Enhancer Genie (LEG), a collection of highly accurate, genome-wide predictions of enhancers in the developing limb, available through a user-friendly online interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28827824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Limb-Enhancer Genie: An accessible resource of accurate enhancer predictions in the developing limb.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28827824", "endSection": "title" } ] }, { "body": "What is the first line treatment for sarcoidosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28696638", "http://www.ncbi.nlm.nih.gov/pubmed/27817209", "http://www.ncbi.nlm.nih.gov/pubmed/26419478", "http://www.ncbi.nlm.nih.gov/pubmed/16536004", "http://www.ncbi.nlm.nih.gov/pubmed/10719453", "http://www.ncbi.nlm.nih.gov/pubmed/17081481", "http://www.ncbi.nlm.nih.gov/pubmed/27421131", "http://www.ncbi.nlm.nih.gov/pubmed/26204816", "http://www.ncbi.nlm.nih.gov/pubmed/10598414", "http://www.ncbi.nlm.nih.gov/pubmed/28056473", "http://www.ncbi.nlm.nih.gov/pubmed/28474323", "http://www.ncbi.nlm.nih.gov/pubmed/23884295", "http://www.ncbi.nlm.nih.gov/pubmed/23880702", "http://www.ncbi.nlm.nih.gov/pubmed/24753153", "http://www.ncbi.nlm.nih.gov/pubmed/29137908", "http://www.ncbi.nlm.nih.gov/pubmed/23538719" ], "triples": [ { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS", "o": "SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13017440", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13021341", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13025099", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13028399", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13040119", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13026973", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13023215", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13019578", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13016434", "o": "http://linkedlifedata.com/resource/pubmed/keyword/SARCOIDOSIS" } ], "ideal_answer": [ "Sarcoidosis is a systemic granulomatous disease that affects numerous organs, commonly manifesting at the lungs and skin. Corticosteroids remain the first line of treatment." ], "exact_answer": [ "Corticosteroids" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D017565", "http://www.disease-ontology.org/api/metadata/DOID:11335", "http://www.disease-ontology.org/api/metadata/DOID:13406", "http://www.disease-ontology.org/api/metadata/DOID:13407", "https://meshb.nlm.nih.gov/record/ui?ui=D012507", "http://www.disease-ontology.org/api/metadata/DOID:13405", "http://www.disease-ontology.org/api/metadata/DOID:13402", "http://www.disease-ontology.org/api/metadata/DOID:13403" ], "type": "factoid", "id": "5a7877c0faa1ab7d2e00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 377, "text": "Sarcoidosis represents a non-caseating, granulomatous disorder of unknown aetiology whose clinical manifestation is heterogeneous and frequently multisystemic. The portion of patients needing systemic treatment varies: though many patients may undergo spontaneous remission, organ-threatening courses demand systemic therapy. Corticosteroids are the first-line treatment option", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28056473", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 443, "text": " The prevalence of cardiac sarcoidosis has exponentially increased over the past decade, primarily due to increased awareness and diagnostic modalities for the disease entity. Despite an expanding patient cohort, the optimal management of cardiac sarcoidosis remains yet to be established with a significant lack of prospective trials to support current practice. Corticosteroids remain first-line treatment of this disorder,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28474323", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 79, "text": "Prednisone is used as first-line therapy for pulmonary sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137908", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 531, "text": "Corticosteroids are still the first-line treatment, but alternative therapy with anti-TNF agents, like pentoxifylline, thalidomide and anti-TNF monoclonal antibodies become more interesting, especially in refractory sarcoidosis.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16536004", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 527, "text": "Corticosteroids are still the first-line treatment, but alternative therapy with anti-TNF agents, like pentoxifylline, thalidomide and anti-TNF monoclonal antibodies become more interesting, especially in refractory sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16536004", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 311, "text": "While corticosteroids remain the first line of treatment, tumour necrosis factor alpha (TNF-\u03b1) inhibitors have been investigated as one potential steroid sparing treatment for sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26419478", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 392, "text": "Systemic corticosteroids are the first line treatment in sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28696638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Although glucocorticosteroids are considered the first-line treatment in sarcoidosis, refractory cases require alternatives, such as methotrexate (MTX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23880702", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1117, "text": "Corticosteroids remain the first-line therapy for sarcoidosis as many patients never require treatment or only necessitate a short treatment duration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23884295", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 528, "text": "Corticosteroids are still the first-line treatment, but alternative therapy with anti-TNF agents, like pentoxifylline, thalidomide and anti-TNF monoclonal antibodies become more interesting, especially in refractory sarcoidosis..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16536004", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1079, "text": "Glucocorticoid treatment is first-line therapy for hepatic sarcoidosis, improving symptoms and abnormal laboratory values but generally having no effect on progression of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17081481", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 124, "text": "Steroids remain the first-choice therapeutic in sarcoidosis; however, long-term use is associated with toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23538719", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 448, "text": "Glucocorticoids are the first-line therapy for sarcoidosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27817209", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 162, "text": "Oral glucocorticoids are the standard first-line treatment for sarcoidosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26204816", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 365, "text": "Corticosteroids are used as first-line treatment in organ-threatening sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24753153", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1233, "text": "Corticosteroids still remain first-line therapy in sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27421131", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 198, "text": " Generally, oral corticosteroids are considered the first-line treatment for symptomatic patients with pulmonary sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10598414", "endSection": "abstract" } ] }, { "body": "Which personality disorder is treated using dialectical behavior therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28119507", "http://www.ncbi.nlm.nih.gov/pubmed/20579633", "http://www.ncbi.nlm.nih.gov/pubmed/27399588", "http://www.ncbi.nlm.nih.gov/pubmed/27897326", "http://www.ncbi.nlm.nih.gov/pubmed/14608551", "http://www.ncbi.nlm.nih.gov/pubmed/27642799", "http://www.ncbi.nlm.nih.gov/pubmed/18186120", "http://www.ncbi.nlm.nih.gov/pubmed/22751905", "http://www.ncbi.nlm.nih.gov/pubmed/9064551", "http://www.ncbi.nlm.nih.gov/pubmed/7977884", "http://www.ncbi.nlm.nih.gov/pubmed/9603574", "http://www.ncbi.nlm.nih.gov/pubmed/17496179", "http://www.ncbi.nlm.nih.gov/pubmed/27481266", "http://www.ncbi.nlm.nih.gov/pubmed/28555557", "http://www.ncbi.nlm.nih.gov/pubmed/21114345", "http://www.ncbi.nlm.nih.gov/pubmed/27959459", "http://www.ncbi.nlm.nih.gov/pubmed/19755574", "http://www.ncbi.nlm.nih.gov/pubmed/27091455" ], "ideal_answer": [ "Dialectical behavior therapy is an evidence-based psychosocial treatment with efficacy in reducing self-harm behaviors in borderline personality disorder." ], "exact_answer": [ "borderline personality disorder" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1510", "https://meshb.nlm.nih.gov/record/ui?ui=D010554", "https://meshb.nlm.nih.gov/record/ui?ui=D001521" ], "type": "factoid", "id": "5a68f005b750ff4455000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Neural correlates of distraction in borderline personality disorder before and after dialectical behavior therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27091455", "endSection": "title" }, { "offsetInBeginSection": 164, "offsetInEndSection": 360, "text": "It is unknown whether neural correlates of emotion regulation change after a psychotherapy which has the goal to improve emotion dysregulation in BPD, such as dialectical behavioral therapy (DBT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27091455", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1688, "text": " In conclusion, our findings reveal changes in neural activity associated with distraction during emotion processing after DBT in patients with BPD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27091455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "ObjectiveInvestigate influence and change of self-directedness (SD) in Dialectical-Behavior Therapy (DBT) for 26 female outpatients with borderline personality disorder (BPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399588", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 603, "text": "ConclusionDBT strengthens the SD of patients with BPD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27399588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "OBJECTIVE: Dialectical behavior therapy (DBT) is an evidence-based psychosocial treatment with efficacy in reducing self-harm behaviors in borderline personality disorder (BPD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481266", "endSection": "abstract" }, { "offsetInBeginSection": 1848, "offsetInEndSection": 2107, "text": "CONCLUSION: This DBT curriculum was effective in preparing psychiatrists-in-training to incorporate evidence-based practices for effective treatment of BPD and self-harm behaviors and can serve as a model for teaching DBT during psychiatry residency training.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Exploring the effectiveness of combined mentalization-based group therapy and dialectical behaviour therapy for inpatients with borderline personality disorder - A pilot study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27897326", "endSection": "title" }, { "offsetInBeginSection": 232, "offsetInEndSection": 511, "text": "Dialectical behaviour therapy (DBT) has proven highly effective in reducing self-harm and improving emotion regulation, whereby problems concerning social cognition, which are also characteristic of BPD, may need additional approaches such as mentalization-based treatment (MBT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27897326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Pain-mediated affect regulation is reduced after dialectical behavior therapy in borderline personality disorder: a longitudinal fMRI study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28119507", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Borderline Personality Disorder (BPD) is characterized by affective instability, but self-injurious behavior appears to have an emotion-regulating effect. We investigated whether pain-mediated affect regulation can be altered at the neural level by residential Dialectical Behavior Therapy (DBT), providing adaptive emotion regulation techniques. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28119507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Use of dialectical behavior therapy in borderline personality disorder: a view from residency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17496179", "endSection": "title" }, { "offsetInBeginSection": 276, "offsetInEndSection": 468, "text": "Of evaluated psychological treatments in borderline personality disorder, dialectical behaviour therapy (DBT) has the strongest research support, followed by mentalization based therapy (MBT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27959459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "The authors describe the use of dialectical behavior therapy (DBT) in treating borderline personality disorder during psychiatry residency, and assess the status of DBT education within psychiatry residencies in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17496179", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 646, "text": "Dialectical behavior therapy (DBT) was originally developed by Marsha Linehan (1991) for the treatment of borderline personality disorder, but because of the core deficits in emotion regulation in disruptive behavior disorders, DBT is also increasingly being recommended for the treatment of CD and APD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27642799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Treatment of suicidal and deliberate self-harming patients with borderline personality disorder using dialectical behavioral therapy: the patients' and the therapists' perceptions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14608551", "endSection": "title" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1554, "text": "Dialectical behavioral therapy and schema-focused therapy also caused a soaring remission rate of diagnostic borderline personality disorder criteria of 57% and 94%, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28555557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: Dialectical behavior therapy (DBT) is an empirically supported treatment for outpatients with borderline personality disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22751905", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "OBJECTIVE The authors describe the use of dialectical behavior therapy (DBT) in treating borderline personality disorder during psychiatry residency, and assess the status of DBT education within psychiatry residencies in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17496179", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1106, "text": "CONCLUSIONS These results suggest that dialectical behavior therapy is a promising psychosocial intervention for improving interpersonal functioning among severely dysfunctional patients with borderline personality disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7977884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "A central component of Dialectical Behavior Therapy (DBT) is the teaching of specific behavioral skills with the aim of helping individuals with Borderline Personality Disorder (BPD) replace maladaptive behaviors with skillful behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20579633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Dialectical behavior therapy (DBT) was originally designed as a treatment of emotionally dysregulated, impulsive, and dramatic disorders (e.g., borderline personality disorder) and populations (e.g., parasuicidal women).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18186120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Dialectical behavior therapy, an outpatient psychosocial treatment for chronically suicidal women with borderline personality disorder, has been adapted for use in a partial hospital program for women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9603574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "OBJECTIVE At present, the most frequently investigated psychosocial intervention for borderline personality disorder (BPD) is dialectical behavior therapy (DBT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21114345", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 117, "text": "Linehan developed \"dialectical behavioral therapy\" specifically to treat chronically suicidal borderline patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9064551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Use of dialectical behavior therapy in borderline personality disorder: a view from residency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17496179", "endSection": "title" }, { "offsetInBeginSection": 1427, "offsetInEndSection": 1681, "text": "These results suggest that individuals with borderline personality disorder benefited equally from dialectical behavior therapy and a well-specified treatment delivered by psychiatrists with expertise in the treatment of borderline personality disorder..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19755574", "endSection": "abstract" } ] }, { "body": "What cellular process are okazaki fragments associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22918592", "http://www.ncbi.nlm.nih.gov/pubmed/227871", "http://www.ncbi.nlm.nih.gov/pubmed/12861020", "http://www.ncbi.nlm.nih.gov/pubmed/19000038", "http://www.ncbi.nlm.nih.gov/pubmed/24035200", "http://www.ncbi.nlm.nih.gov/pubmed/9580686", "http://www.ncbi.nlm.nih.gov/pubmed/21441898", "http://www.ncbi.nlm.nih.gov/pubmed/12806117", "http://www.ncbi.nlm.nih.gov/pubmed/21278448", "http://www.ncbi.nlm.nih.gov/pubmed/27989437", "http://www.ncbi.nlm.nih.gov/pubmed/14693726", "http://www.ncbi.nlm.nih.gov/pubmed/25814667", "http://www.ncbi.nlm.nih.gov/pubmed/20131965", "http://www.ncbi.nlm.nih.gov/pubmed/26175049", "http://www.ncbi.nlm.nih.gov/pubmed/28301743", "http://www.ncbi.nlm.nih.gov/pubmed/20178844", "http://www.ncbi.nlm.nih.gov/pubmed/11710514", "http://www.ncbi.nlm.nih.gov/pubmed/22419157", "http://www.ncbi.nlm.nih.gov/pubmed/23792162", "http://www.ncbi.nlm.nih.gov/pubmed/28159842", "http://www.ncbi.nlm.nih.gov/pubmed/25916711", "http://www.ncbi.nlm.nih.gov/pubmed/28496054", "http://www.ncbi.nlm.nih.gov/pubmed/12228807", "http://www.ncbi.nlm.nih.gov/pubmed/14690413" ], "ideal_answer": [ "Okazaki fragments are involved in DNA replication" ], "exact_answer": [ "DNA replication" ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0006273", "http://amigo.geneontology.org/amigo/term/GO:1903461", "http://amigo.geneontology.org/amigo/term/GO:1903459" ], "type": "factoid", "id": "5a79d0b8faa1ab7d2e00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 607, "text": "This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase \u03b5 (Pol \u03b5) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases \u03b1 and \u03b4 carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28301743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 721, "text": "At DNA replication forks, the overall growth of the antiparallel two daughter DNA chains appears to occur 5'-to-3' direction in the leading-strand and 3'-to-5' direction in the lagging-strand using enzyme system only able to elongate 5'-to-3' direction, and I describe in this review how we have analyzed and proved the lagging strand multistep synthesis reactions, called Discontinuous Replication Mechanism, which involve short RNA primer synthesis, primer-dependent short DNA chains (Okazaki fragments) synthesis, primer removal from the Okazaki fragments and gap filling between Okazaki fragments by RNase H and DNA polymerase I, and long lagging strand formation by joining between Okazaki fragments with DNA ligase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28496054", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 368, "text": "Therefore, efficient processing of Okazaki fragments is vital for DNA replication and cell proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21278448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "RNA primer removal from Okazaki fragments during lagging-strand replication and the excision of damaged DNA bases requires the action of structure-specific nucleases, such as the mammalian flap endonuclease 1 (FEN-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12228807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Lagging strand DNA replication requires the concerted actions of DNA polymerase \u03b4, Fen1 and DNA ligase I for the removal of the RNA/DNA primers before ligation of Okazaki fragments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "During DNA replication in eukaryotic cells, short single-stranded DNA segments known as Okazaki fragments are first synthesized on the lagging strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28159842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "During DNA replication, repetitive synthesis of discrete Okazaki fragments requires mechanisms that guarantee DNA polymerase, clamp, and primase proteins are present for every cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21441898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 509, "text": "DNA replication is a primary mechanism for maintaining genome integrity, but it serves this purpose best by cooperating with other proteins involved in DNA repair and recombination. Unlike leading strand synthesis, lagging strand synthesis has a greater risk of faulty replication for several reasons: First, a significant part of DNA is synthesized by polymerase alpha, which lacks a proofreading function. Second, a great number of Okazaki fragments are synthesized, processed and ligated per cell division.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20131965", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 713, "text": "Lagging strand replication involves a very complex set of interacting proteins that are able to frequently initiate, elongate and process Okazaki fragments of 180 bp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11710514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "FENs (flap endonucleases) play essential roles in DNA replication, pivotally in the resolution of Okazaki fragments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19000038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Flap endonuclease 1 (FEN1) has been shown to remove 5' overhanging flap intermediates during base excision repair and to process the 5' ends of Okazaki fragments during lagging-strand DNA replication in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12861020", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 410, "text": "Frequent priming of the discontinuous strand results in the formation of many small segments, designated Okazaki fragments. These short pieces need to be processed and joined to form an intact DNA strand", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14693726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "During DNA replication, synthesis of the lagging strand occurs in stretches termed Okazaki fragments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26175049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Fifty per cent of the genome is discontinuously replicated on the lagging strand as Okazaki fragments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25814667", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 416, "text": "Even though synthesis and joining of Okazaki fragments on the lagging strand involves only half the DNA in the nucleus, the complexity associated with processing these fragments is about twice that needed for leading strand synthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20178844", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 453, "text": "Okazaki fragments that are intermediates during DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9580686", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 681, "text": "Deep sequencing of Okazaki fragments generates a comprehensive, genomic map of DNA synthesis, starting from a single asynchronous culture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25916711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Essentially all of the Okazaki fragments on replicating Simian virus 40 (SV40)DNA could be grouped into one of three classes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/227871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Genome-wide Okazaki fragment distribution can differentiate the discontinuous from the semi-discontinuous DNA replication model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23792162", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 707, "text": "We uncover a dual regulatory role for chromatin during DNA replication: promoting origin dependence and determining Okazaki fragment length by restricting Pol \u03b4 progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27989437", "endSection": "abstract" } ] }, { "body": "Does wheat belongs to the genus Avena, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29146257", "http://www.ncbi.nlm.nih.gov/pubmed/10984842", "http://www.ncbi.nlm.nih.gov/pubmed/27079356", "http://www.ncbi.nlm.nih.gov/pubmed/11908651", "http://www.ncbi.nlm.nih.gov/pubmed/11536867", "http://www.ncbi.nlm.nih.gov/pubmed/20658121", "http://www.ncbi.nlm.nih.gov/pubmed/26618715", "http://www.ncbi.nlm.nih.gov/pubmed/28132155", "http://www.ncbi.nlm.nih.gov/pubmed/28132141", "http://www.ncbi.nlm.nih.gov/pubmed/24226111" ], "ideal_answer": [ "oat seedlings (Avena sativa)", "Wheat belongs to the species Triticum not to the genus Avena.", "oat seedlings (Avena sativa). " ], "exact_answer": "no", "type": "yesno", "id": "5a79d25dfaa1ab7d2e00000f", "snippets": [ { "offsetInBeginSection": 84, "offsetInEndSection": 112, "text": "oat seedlings (Avena sativa)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29146257", "endSection": "title" }, { "offsetInBeginSection": 19, "offsetInEndSection": 49, "text": "wild green-oat (Avena sativa) ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26618715", "endSection": "title" }, { "offsetInBeginSection": 74, "offsetInEndSection": 96, "text": " Oat (Avena sativa L.)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28132141", "endSection": "abstract" }, { "offsetInBeginSection": 38, "offsetInEndSection": 59, "text": "Oat (Avena sativa L.)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28132155", "endSection": "title" }, { "offsetInBeginSection": 46, "offsetInEndSection": 58, "text": "Avena (Oats)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24226111", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 142, "text": "wild oats (Avena fatua L.)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27079356", "endSection": "abstract" }, { "offsetInBeginSection": 41, "offsetInEndSection": 59, "text": "oats (genus Avena)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10984842", "endSection": "title" }, { "offsetInBeginSection": 46, "offsetInEndSection": 88, "text": "Avena sativa L. and A. byzantina C. Koch) ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20658121", "endSection": "title" }, { "offsetInBeginSection": 81, "offsetInEndSection": 104, "text": " oat (Avena sativa L.).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11908651", "endSection": "title" }, { "offsetInBeginSection": 16, "offsetInEndSection": 66, "text": "oat (Avena sativa L.) and wheat (Triticum aestivum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11536867", "endSection": "abstract" } ] }, { "body": "Clue cells are characteristics to which causative bacteria of vaginitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11025268", "http://www.ncbi.nlm.nih.gov/pubmed/18459549", "http://www.ncbi.nlm.nih.gov/pubmed/10948822", "http://www.ncbi.nlm.nih.gov/pubmed/20006195", "http://www.ncbi.nlm.nih.gov/pubmed/11845812", "http://www.ncbi.nlm.nih.gov/pubmed/22555524", "http://www.ncbi.nlm.nih.gov/pubmed/20949462" ], "ideal_answer": [ "Clue cells are characteristic to Gardnerella vaginalis vaginitis (bacterial vaginosis). Depopulation of lactobacilli from the normal vaginal flora and overgrowth of Gardnerella vaginalis and other anaerobic species are the presumed etiology. The diagnosis is confirmed when at least three of the following four findings are present (Amsel's criteria): 1) thin, homogenous discharge, 2) pH greater than 4.5, 3) positive amine test, and 4) presence of clue cell." ], "exact_answer": [ "Gardnerella vaginalis" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014627", "http://www.disease-ontology.org/api/metadata/DOID:2170" ], "type": "factoid", "id": "5a68f965b750ff445500001a", "snippets": [ { "offsetInBeginSection": 921, "offsetInEndSection": 1030, "text": "Most of these 290 smears contained clue cells (indicating Gardnerella infection) and a lack of lactobacilli. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20949462", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 487, "text": "As part of the routine screening process, all smears were screened for the overgrowth of Gardnerella (i.e. smears with an abundance of clue cells) and for the presence of Trichomonas and Candida.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22555524", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 722, "text": "Positive criteria for a Gram stain included greater than 10 white blood cells per high-power field, gram-negative intracellular/extracellular diplococci (suggesting N gonorrhoeae), clue cells (suggesting T vaginalis), or direct visualization of T vaginalis organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20006195", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 373, "text": "he appraised infectious agents were Coccobacilli, Candida sp, Trichomonas vaginalis, and clue cells (Gardnerella vaginalis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18459549", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 540, "text": "Smears deficient in lactobacilli and positive for clue cells were considered to indicate a diagnosis of bacterial vaginosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11845812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 746, "text": "Bacterial vaginosis is the most common cause of vaginitis, affecting over 3 million women in the United States annually. Depopulation of lactobacilli from the normal vaginal flora and overgrowth of Gardnerella vaginalis and other anaerobic species are the presumed etiology. To date, no scientific evidence shows that bacterial vaginosis is a sexually transmitted disease. Malodorous vaginal discharge is the most common symptom. Differential diagnoses include trichomoniasis, moniliasis, and allergic or chemical dermatitis. The diagnosis is confirmed when at least three of the following four findings are present (Amsel's criteria): 1) thin, homogenous discharge, 2) pH greater than 4.5, 3) positive amine test, and 4) presence of clue cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11025268", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1189, "text": "Although the presence of clue cells and amine-like odor in KOH test have relationship with Gardnerella vaginalis, these tests could also suggest the presence of these mycoplasmas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10948822", "endSection": "abstract" } ] }, { "body": "What is included in the fourth generation HIV test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27272704", "http://www.ncbi.nlm.nih.gov/pubmed/28501753", "http://www.ncbi.nlm.nih.gov/pubmed/28872273", "http://www.ncbi.nlm.nih.gov/pubmed/28872274", "http://www.ncbi.nlm.nih.gov/pubmed/24856744", "http://www.ncbi.nlm.nih.gov/pubmed/26936099", "http://www.ncbi.nlm.nih.gov/pubmed/28710996", "http://www.ncbi.nlm.nih.gov/pubmed/11595590", "http://www.ncbi.nlm.nih.gov/pubmed/28846743", "http://www.ncbi.nlm.nih.gov/pubmed/28931369", "http://www.ncbi.nlm.nih.gov/pubmed/28273857" ], "ideal_answer": [ "Fourth generation assays detect simultaneously antibodies for HIV and the p24 antigen. It identifies HIV infection earlier than previous generation tests." ], "exact_answer": [ [ "antibodies for HIV" ], [ "p24 antigen" ] ], "type": "list", "id": "5a68fd01b750ff445500001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Diagnosing acute HIV infection at point of care: a retrospective analysis of the sensitivity and specificity of a fourth-generation point-of-care test for detection of HIV core protein p24.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27272704", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 518, "text": "Previous evaluation of the fourth-generation Alere Determine HIV-1/2 Ag/Ab Combo POCT showed only 50% sensitivity for HIV core protein p24 (p24 antigen) detection, which is suboptimal for diagnosis of acute HIV infection with limited advantage over third-generation POCT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27272704", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1282, "text": "CONCLUSIONS: This new POCT shows improved sensitivity for detection of p24 antigen and may be of value for clinical use in detecting acute HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27272704", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 551, "text": "While fourth generation antigen-antibody combination assays have been successful in high-resource settings, rapid point of care (POC) versions of these assays have yet to demonstrate high sensitivity to detect AHI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28273857", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 624, "text": "STUDY DESIGN: A total of 30,201 sera were tested for HIV diagnosis using Abbott Architect\u00aeHIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28501753", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 460, "text": "OBJECTIVE: To determine if fourth-generation antigen/antibody (Ag/Ab) rapid diagnostic tests (RDT) would have detected HIV infection earlier than the third-generation RDT used in MTN-003 (VOICE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28710996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "BACKGROUND: Fourth generation assays detect simultaneously antibodies for HIV and the p24 antigen, identifying HIV infection earlier than previous generation tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846743", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1187, "text": "The status of clients on ART was additionally confirmed by fourth-generation HIV Ag/Ab combo tests, Architect and Genscreen Ultra.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28872273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "INTRODUCTION: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28872274", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1021, "text": "The sample was later routinely tested with a fourth generation antigen/antibody assay as per local protocol and was strongly positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931369", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 975, "text": "The fourth-generation HIV EIA was positive presumably because it detects p24 HIV antigen as well as antibodies, unlike rapid HIV tests and third-generation HIV EIAs.This case highlights not only the importance of frontline providers to understand the different testing methodologies for HIV screening and their limitations but the importance of clinical suspicion as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856744", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1260, "text": "This second diagnostic window was caused by the absence of HIV specific antibodies and the decline of HIV p24 antigen concentrations below the detection limits of the fourth generation assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11595590", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 805, "text": "Fourth- and fifth-generation HIV assays added p24 antigen detection to the screening assay, reducing the test-negative window to 11 to 14 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26936099", "endSection": "abstract" } ] }, { "body": "Which disease is diagnosed using the Finkelstein's test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26645452", "http://www.ncbi.nlm.nih.gov/pubmed/19939537", "http://www.ncbi.nlm.nih.gov/pubmed/19588376", "http://www.ncbi.nlm.nih.gov/pubmed/12723309", "http://www.ncbi.nlm.nih.gov/pubmed/17059194", "http://www.ncbi.nlm.nih.gov/pubmed/23340762", "http://www.ncbi.nlm.nih.gov/pubmed/15680568", "http://www.ncbi.nlm.nih.gov/pubmed/24139754", "http://www.ncbi.nlm.nih.gov/pubmed/18956185" ], "ideal_answer": [ "Finkelstein's test is the classic diagnostic test for de Quervain's disease." ], "exact_answer": [ "de Quervain's disease" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004194", "https://meshb.nlm.nih.gov/record/ui?ui=D003933" ], "type": "factoid", "id": "5a6900ebb750ff445500001d", "snippets": [ { "offsetInBeginSection": 586, "offsetInEndSection": 834, "text": "The inclusion criteria were positive Finkelstein's test and no response to non-surgical treatment for 6 weeks. Forty-eight patients with de Quervain's disease who did not respond to conservative treatment were operated with two different incisions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26645452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "De Quervain's disease has different clinical features. Different tests have been described in the past, the most popular test being the Eichhoff's test, often wrongly named as the Finkelstein's test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23340762", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 1083, "text": "Furthermore, we found that Finkelstein's test can give a false positive result. Therefore, ultrasound should not only be considered to improve the treatment outcome, but can also be useful as a diagnostic tool in the management of de Quervain's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24139754", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 572, "text": "The Finkelstein's test was positive in all cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19939537", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 887, "text": "A successful outcome was achieved in all cases with negative Finkelstein's test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18956185", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1546, "text": "We extracted data on the primary outcome measures: treatment success; severity of pain or tenderness at the radial styloid; functional impairment of the wrist or hand; and outcome of Finkelstein's test, and the secondary outcome measures: proportion of patients with side effects; type of side effects and patient satisfaction with injection treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19588376", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 291, "text": "Finkelstein's test is pathognomonic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17059194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "PURPOSE: Finkelstein's test is the classic diagnostic test for de Quervain's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15680568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "[Finkelstein's versus Brunelli's test in De Quervain tenosynovitis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12723309", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "This short paper demonstrates that the Finkelstein's test in De Quervain's tenosynovitis is based on an incorrect assumption. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12723309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Finkelstein's test is the classic diagnostic test for de Quervain's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15680568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "PURPOSE: Finkelstein's test is the classic diagnostic test for de Quervain's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15680568", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 85, "text": "Finkelstein's test is the classic diagnostic test for de Quervain's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15680568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "PURPOSE Finkelstein's test is the classic diagnostic test for de Quervain's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15680568", "endSection": "abstract" } ] }, { "body": "For which type of cancer can uc.189 be used as a potential prognostic biomarker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28941722" ], "ideal_answer": [ "ESCC", "High expression of uc.189 might reflect poor prognosis of Esophageal squamous cell carcinomas (ESCC) and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.", "Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target." ], "exact_answer": [ "Esophageal squamous cell carcinomas (ESCC)" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D054316", "https://meshb.nlm.nih.gov/record/ui?ui=D015415", "https://meshb.nlm.nih.gov/record/ui?ui=D014408" ], "type": "factoid", "id": "5a6e1280b750ff4455000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Upregulation of uc.189 in patients with esophageal squamous cell carcinoma and its clinicopathologic value.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 1272, "text": "This study was to identify the prognostic value of uc.189 expression in esophageal squamous cell carcinomas (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC. The correlation of uc.189 with clinicopathological features and prognosis were also analyzed. The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis. High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 371, "text": "This study was to identify the prognostic value of uc.189 expression in esophageal squamous cell carcinomas (ESCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 572, "text": "Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 999, "text": "The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1123, "text": "High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1276, "text": "Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1272, "text": "Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1273, "text": "Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" } ] }, { "body": "Does Uc.160 promote cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "http://www.ncbi.nlm.nih.gov/pubmed/20802525" ], "ideal_answer": [ "No. Uc.160+ is a T-UCR reported to be downregulated in human cancer. In addition, Uc.160+ could possibly have a tumor suppressive role in gastric cancer." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:162", "https://meshb.nlm.nih.gov/record/ui?ui=D009369" ], "type": "yesno", "id": "5a6d2558b750ff4455000036", "snippets": [ { "offsetInBeginSection": 245, "offsetInEndSection": 1592, "text": "We previously discovered the downregulation of T-UCR expression in gastric cancer (GC), indicating that T-UCRs could play an important role in GC biology. Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.METHODS: We analyzed the expression pattern of Uc.160+ in nonneoplastic and tumor tissues of the stomach by using uantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), specifically focusing on the mechanism of transcriptional regulation and target genes that are regulated by T-UCRs. We also attempted to determine the effect of Uc.160+ expression on biological features of GC cell lines by Western blotting.RESULTS: On the basis of the qRT-PCR and ISH results, Uc.160+ expression in adenoma and GC tissues was clearly downregulated compared with that in nonneoplastic mucosa tissues of the stomach. Cancer-specific DNA methylation in the promoter region of Uc.160 was observed by bisulfite genomic DNA sequencing analysis. The effect of DNA methylation on Uc.160+ expression was further confirmed by reporter gene assay. We also revealed that Uc.160+ inhibited the phosphorylation of Akt by regulating phosphatase and tensin homolog (PTEN) expression.CONCLUSIONS: These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 841, "text": "Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.
METHODS: We analyzed the expression pattern of Uc.160+ in nonneoplastic and tumor tissues of the stomach by using uantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), specifically focusing on the mechanism of transcriptional regulation and target genes that are regulated by T-UCRs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 1391, "offsetInEndSection": 1636, "text": "We also revealed that Uc.160+ inhibited the phosphorylation of Akt by regulating phosphatase and tensin homolog (PTEN) expression.
CONCLUSIONS: These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1168, "text": "We also attempted to determine the effect of Uc.160+ expression on biological features of GC cell lines by Western blotting.
RESULTS: On the basis of the qRT-PCR and ISH results, Uc.160+ expression in adenoma and GC tissues was clearly downregulated compared with that in nonneoplastic mucosa tissues of the stomach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 1498, "offsetInEndSection": 1597, "text": "CONCLUSIONS These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 490, "text": "Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1494, "text": "Among the T-UCRs that were reactivated upon drug treatment, Uc.160+, Uc283+A and Uc.346+ were found to undergo specific CpG island hypermethylation-associated silencing in cancer cells compared with normal tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20802525", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 479, "text": "Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1553, "text": "These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" } ] }, { "body": "What causes Black Lung?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6453959", "http://www.ncbi.nlm.nih.gov/pubmed/8803434", "http://www.ncbi.nlm.nih.gov/pubmed/8199664", "http://www.ncbi.nlm.nih.gov/pubmed/8456342" ], "ideal_answer": [ "Black lung, also known as pneumoconiosis, is caused by chronic exposure to coal dust." ], "exact_answer": [ "Chronic exposure to coal dust" ], "type": "factoid", "id": "5a87145861bb38fb24000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "A prospective case-control study was undertaken to assess respiratory disability in 133 former coal miners who were claimants for \"black lung\" benefits. Consecutive assignment was made to either case or control group based on their chest radiograph having shown coal workers' pneumoconiosis or no coal workers' pneumoconiosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8803434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "It has recently been suggested that the inhalation of coal in the absence of complicated coal workers' pneumoconiosis (CWP) or smoking can lead to disabling airways obstruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8199664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 494, "text": "Highlights in the history of efforts to prevent occupational lung disease among coal miners in the United States are reviewed. The Federal Coal Mine Health and Safety Act of 1969 is summarized, and the sources and effects of its provisions to prevent coal workers' pneumoconiosis are examined. Descriptions follow of the identification of coal workers' pneumoconiosis as a disease, identification of respirable coal mine dust as its cause, and establishment and enforcement of an exposure limit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8456342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Coal workers' pneumoconiosis is a preventable occupational disorder of the respiratory system resulting from exposure to and retention of respirable coal dust. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6453959", "endSection": "abstract" } ] }, { "body": "List four principles of medical ethics.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25516950", "http://www.ncbi.nlm.nih.gov/pubmed/18316452", "http://www.ncbi.nlm.nih.gov/pubmed/21625670", "http://www.ncbi.nlm.nih.gov/pubmed/22438579", "http://www.ncbi.nlm.nih.gov/pubmed/25028113", "http://www.ncbi.nlm.nih.gov/pubmed/21937467", "http://www.ncbi.nlm.nih.gov/pubmed/10402417", "http://www.ncbi.nlm.nih.gov/pubmed/23975951", "http://www.ncbi.nlm.nih.gov/pubmed/24720355", "http://www.ncbi.nlm.nih.gov/pubmed/26793677", "http://www.ncbi.nlm.nih.gov/pubmed/22606995", "http://www.ncbi.nlm.nih.gov/pubmed/17526683", "http://www.ncbi.nlm.nih.gov/pubmed/18552646", "http://www.ncbi.nlm.nih.gov/pubmed/28601921" ], "ideal_answer": [ "The four principles of medical ethics proposed by Beauchamp and Childress are autonomy, non-maleficence, beneficence and justice. They have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care." ], "exact_answer": [ [ "autonomy" ], [ "non-maleficence" ], [ "beneficence" ], [ "justice" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004992" ], "type": "list", "id": "5a6f7e6ab750ff4455000052", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Respect for Autonomy (RFA) has been a mainstay of medical ethics since its enshrinement as one of the four principles of biomedical ethics by Beauchamp and Childress' in the late 1970s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28601921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "There are four principles of medical ethics; Beneficence, Respect for autonomy, Non-maleficence, and Justice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26793677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "This paper argues that the four prima facie principles-beneficence, non-maleficence, respect for autonomy and justice-afford a good and widely acceptable basis for 'doing good medical ethics'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Contemporary clinical ethics was founded on principlism, and the four principles: respect for autonomy, nonmaleficence, beneficence and justice, remain dominant in medical ethics discourse and practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24720355", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 745, "text": "Each of the four principles (beneficence, nonmaleficence,justice and autonomy) is investigated in turn, looking in particular at the extent to which each is rooted in the Islamic paradigm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23975951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 443, "text": "Guided by the medical ethics principles of \"four principles plus scope,\" Chinese aesthetic medical practitioners have proposed some extremely valuable ethical principles combined with the construction of aesthetic medicine and the requirements of clinical practice such as the principle of general nonmaleficence, the principle of local minimal invasiveness, the principle of informed consent, and the principle of respect and confidentiality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25028113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 523, "text": "This commentary briefly argues that the four prima facie principles of beneficence, non-maleficence, respect for autonomy and justice enable a clinician (and anybody else) to make ethical sense of the author's proposed reliance on professional guidance and rules, on law, on professional integrity and on best interests, and to subject them all to ethical analysis and criticism based on widely acceptable basic prima facie moral obligations; and also to confront new situations in the light of those acceptable principles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22438579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22606995", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 846, "text": "Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21625670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 437, "text": "Tom Beauchamp and James Childress have always maintained that their four principles approach (otherwise known as principlism) is a globally applicable framework for biomedical ethics. This claim is grounded in their belief that the principles of respect for autonomy, non-maleficence, beneficence and justice form part of a 'common morality', or collection of very general norms to which everyone who is committed to morality subscribes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21937467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 531, "text": "I will argue that there are difficulties with the application of the four principles approach to incompetent children. The most important principle - respect for autonomy - is not directly applicable to incompetent children and the most appropriate modification of the principle for them is not clear. The principle of beneficence - that one should act in the child's interests - is complicated by difficulties in assessing what a child's interests are and to which standard of interests those choosing for children should be held.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18316452", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 253, "text": "These principles are: respect for autonomy, beneficence, non-maleficence and justice, along with concern for their scope of application.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17526683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "BACKGROUND: The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22606995", "endSection": "title" }, { "offsetInBeginSection": 680, "offsetInEndSection": 845, "text": "Difficulties with the application of the four principles (autonomy, beneficence, nonmaleficence and justice) to judge medical practitioner behaviour are highlighted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21625670", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 321, "text": "Four main principles underlie medical ethics: autonomy, nonmaleficence, beneficence, and justice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18552646", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 352, "text": "This approach to treatment is discussed in the context of the four principles of medical ethics, namely respect for autonomy, justice, beneficence and non-maleficence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10402417", "endSection": "abstract" } ] }, { "body": "Which package in Bioconductor has been developed with the aim to analyze differential DNA loops from sequencing data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028898" ], "ideal_answer": [ "Diffloop is an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops.", "diffloop" ], "exact_answer": [ "Diffloop" ], "type": "factoid", "id": "5a6e2578b750ff445500003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "diffloop: a computational framework for identifying and analyzing differential DNA loops from sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028898", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 541, "text": "To systematically assess changes in DNA looping architecture between samples, we introduce diffloop, an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028898", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 539, "text": "To systematically assess changes in DNA looping architecture between samples, we introduce diffloop, an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "diffloop: a computational framework for identifying and analyzing differential DNA loops from sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028898", "endSection": "title" }, { "offsetInBeginSection": 280, "offsetInEndSection": 531, "text": "To systematically assess changes in DNA looping architecture between samples, we introduce diffloop, an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028898", "endSection": "abstract" } ] }, { "body": "Which disease can be diagnosed with the \"probe to bone\" test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28440774", "http://www.ncbi.nlm.nih.gov/pubmed/20622159", "http://www.ncbi.nlm.nih.gov/pubmed/27369321", "http://www.ncbi.nlm.nih.gov/pubmed/17259493", "http://www.ncbi.nlm.nih.gov/pubmed/26804367", "http://www.ncbi.nlm.nih.gov/pubmed/18285592", "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "http://www.ncbi.nlm.nih.gov/pubmed/26009740", "http://www.ncbi.nlm.nih.gov/pubmed/24857262", "http://www.ncbi.nlm.nih.gov/pubmed/23001730" ], "ideal_answer": [ "Probe-to-bone test is used for the diagnosis of diabetic foot osteomyelitis. The test has good sensitivity and specificity. Other diagnostic tests of diabetic foot osteomyelitis are plain films and magnetic resonance imaging." ], "exact_answer": [ "diabetic foot osteomyelitis" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D003933", "https://meshb.nlm.nih.gov/record/ui?ui=D004194" ], "type": "factoid", "id": "5a6f853ab750ff4455000055", "snippets": [ { "offsetInBeginSection": 552, "offsetInEndSection": 698, "text": "Clinical inflammatory signs, probe-to-bone test, and plain X-rays are postulated as the basic tests for clinical diagnosis when DFO is suspected. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28440774", "endSection": "abstract" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1773, "text": "In patients with a new DFU, we recommend probe to bone test and plain films to be followed by magnetic resonance imaging if a soft tissue abscess or osteomyelitis is suspected. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26804367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Diagnostic Accuracy of Probe to Bone to Detect Osteomyelitis in the Diabetic Foot: A Systematic Review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27369321", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "The probe-to-bone (PTB) test is a commonly used clinical test for osteomyelitis (OM), but its utility has been questioned in clinical settings where the prevalence of OM is low. This article aims to systematically review the accuracy of the PTB test to diagnose diabetic foot OM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27369321", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 878, "text": "Pooled sensitivity and specificity for the PTB test was 0.87 (95% confidence interval [CI], .75-.93) and 0.83 (95% CI, .65-.93), respectively. We conclude that the PTB test can accurately rule in diabetic foot OM in the high-risk patients and rule out OM in low-risk patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27369321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Inter-observer reproducibility of diagnosis of diabetic foot osteomyelitis based on a combination of probe-to-bone test and simple radiography.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24857262", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Probe-to-bone test and simple X-rays are both standard tests for the diagnosis of diabetic foot osteomyelitis. This study demonstrates the importance of considering jointly clinical information (probe-to-bone test) and diagnostic tests (simple radiography) to increase agreement among clinicians on diagnosis of diabetic foot osteomyelitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24857262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 473, "text": "Magnetic resonance imaging (MRI) has a higher sensitivity and specificity (90% and 79%) than plain radiography (54% and 68%) for diagnosing diabetic foot osteomyelitis. MRI performs somewhat better than any of several common tests--probe to bone (PTB), erythrocyte sedimentation rate (ESR)>70 mm/hr, C-reactive protein (CRP)>14 mg/L, procalcitonin>0.3 ng/mL, and ulcer size>2 cm\u00b2--although PTB has the highest specificity of any test and is commonly used together with MRI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009740", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "AIMS: To investigate the accuracy of the sequential combination of the probe-to-bone test and plain X-rays for diagnosing osteomyelitis in the foot of patients with diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "abstract" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1149, "text": "RESULTS: Overall, 72.4% of patients had histologically proven osteomyelitis, 85.2% of whom had positive bone culture. The performance characteristics of both the probe-to-bone test and plain X-rays were excellent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1745, "text": "CONCLUSIONS: Clinicians seeing patients in a setting similar to ours (specialized diabetic foot unit with a high prevalence of osteomyelitis) can confidently diagnose diabetic foot osteomyelitis when either the probe-to-bone test or a plain X-ray, or especially both, are positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 469, "text": "The tests assessed were probe-to-bone (PTB), clinical signs of infection, radiography signs of osteomyelitis, and ulcer specimen culture.
RESEARCH DESIGN AND METHODS: A prospective study was performed on patients with foot ulcers referred to our diabetic foot clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20622159", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1720, "text": "Among the tests compared, the best results were yielded by the PTB test including an efficiency of 94%, sensitivity of 98%, specificity of 78%, positive predictive value of 95%, and negative predictive value of 91% (P < 0.001, \u03ba 0.803); the positive likelihood ratio was 4.41, and the negative likelihood ratio was 0.02 (95% CI).
CONCLUSIONS: In our outpatient population with a high prevalence of osteomyelitis, the PTB test was of greatest diagnostic value, especially for neuropathic ulcers, and proved to be efficient for detecting osteomyelitis in the diabetic foot.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20622159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Probe-to-bone test for diagnosing diabetic foot osteomyelitis: reliable or relic?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17259493", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Diagnostic Accuracy of Probe to Bone to Detect Osteomyelitis in the Diabetic Foot:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27369321", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "OBJECTIVE: We sought to assess the accuracy of the probe-to-bone (PTB) test in diagnosing foot osteomyelitis in a cohort of diabetic patients with bone culture proven disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17259493", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Validating the probe-to-bone test and other tests for diagnosing chronic osteomyelitis in the diabetic foot.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20622159", "endSection": "title" }, { "offsetInBeginSection": 2757, "offsetInEndSection": 3022, "text": "An ulcer area larger than 2 cm2, a positive probe-to-bone test result, an erythrocyte sedimentation rate of more than 70 mm/h, and an abnormal plain radiograph result are helpful in diagnosing the presence of lower extremity osteomyelitis in patients with diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18285592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The probe-to-bone (PTB) test is a commonly used clinical test for osteomyelitis (OM), but its utility has been questioned in clinical settings where the prevalence of OM is low.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27369321", "endSection": "abstract" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1750, "text": "CONCLUSIONS Clinicians seeing patients in a setting similar to ours (specialized diabetic foot unit with a high prevalence of osteomyelitis) can confidently diagnose diabetic foot osteomyelitis when either the probe-to-bone test or a plain X-ray, or especially both, are positive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "AIMS To investigate the accuracy of the sequential combination of the probe-to-bone test and plain X-rays for diagnosing osteomyelitis in the foot of patients with diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "OBJECTIVE We sought to assess the accuracy of the probe-to-bone (PTB) test in diagnosing foot osteomyelitis in a cohort of diabetic patients with bone culture proven disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17259493", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1681, "text": "Wound area and depth were not found to be statistically significantly different between groups.
CONCLUSIONS: Positive probe-to-bone test results and erythrocyte sedimentation rates greater than 70 mm/h provide some support for the diagnosis of diabetic foot osteomyelitis, but it is not strong; magnetic resonance imaging or bone biopsy will probably be required in cases of doubt.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 629, "text": "BACKGROUND: We investigated the validity of probe-to-bone testing in the diagnosis of osteomyelitis in a selected subgroup of patients clinically suspected of having diabetic foot osteomyelitis.
METHODS: Between January 1, 2007, and December 31, 2008, inpatients and outpatients with a diabetic foot ulcer were prospectively evaluated, and those having a clinical diagnosis of foot infection and at least one of the osteomyelitis clinical suspicion criteria were consecutively included in this study.
RESULTS: Sixty-five patients met the inclusion criteria and were prospectively enrolled in the study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23001730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "We sought to assess the accuracy of the probe-to-bone (PTB) test in diagnosing foot osteomyelitis in a cohort of diabetic patients with bone culture proven disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17259493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Probe-to-bone test for diagnosing diabetic foot osteomyelitis: reliable or relic?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17259493", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Validating the probe-to-bone test and other tests for diagnosing chronic osteomyelitis in the diabetic foot.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20622159", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Diagnosing diabetic foot osteomyelitis: is the combination of probe-to-bone test and plain radiography sufficient for high-risk inpatients?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "To investigate the accuracy of the sequential combination of the probe-to-bone test and plain X-rays for diagnosing osteomyelitis in the foot of patients with diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1712, "text": "Clinicians seeing patients in a setting similar to ours (specialized diabetic foot unit with a high prevalence of osteomyelitis) can confidently diagnose diabetic foot osteomyelitis when either the probe-to-bone test or a plain X-ray, or especially both, are positive..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Probe-to-bone test and simple X-rays are both standard tests for the diagnosis of diabetic foot osteomyelitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24857262", "endSection": "abstract" } ] }, { "body": "Can doxycycline cause photosensitivity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26816569", "http://www.ncbi.nlm.nih.gov/pubmed/17315050", "http://www.ncbi.nlm.nih.gov/pubmed/17160610", "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "http://www.ncbi.nlm.nih.gov/pubmed/29083100", "http://www.ncbi.nlm.nih.gov/pubmed/10233667", "http://www.ncbi.nlm.nih.gov/pubmed/15262663", "http://www.ncbi.nlm.nih.gov/pubmed/23182067", "http://www.ncbi.nlm.nih.gov/pubmed/26299894", "http://www.ncbi.nlm.nih.gov/pubmed/26189561" ], "ideal_answer": [ "Yes, one of the most important dermatologic side effects of doxycycline is photosensitivity. Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis." ], "exact_answer": "yes", "concepts": [ "http://www.biosemantics.org/jochem#4069681", "http://www.biosemantics.org/jochem#4272840", "https://meshb.nlm.nih.gov/record/ui?ui=D004318" ], "type": "yesno", "id": "5a69031bb750ff445500001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "BACKGROUND: One of the most important dermatologic side effects of doxycycline is photosensitivity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 402, "text": "While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 911, "text": "Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "endSection": "abstract" }, { "offsetInBeginSection": 1233, "offsetInEndSection": 1407, "text": "CONCLUSION: Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "endSection": "abstract" }, { "offsetInBeginSection": 5967, "offsetInEndSection": 6364, "text": "Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29083100", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 564, "text": "Many drugs are responsible for this phototoxic reaction, especially tetracyclines, psoralens, chloramphenicol, non-steroidal anti-inflammatory drugs, fluoroquinolones, and, rarely, doxycycline. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26816569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "OBJECTIVES: Many patients undergoing long-term doxycycline treatment do not regularly take their treatment because of photosensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26299894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Modulation of Melanogenesis and Antioxidant Status of Melanocytes in Response to Phototoxic Action of Doxycycline.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26189561", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Doxycycline is a commonly used tetracycline antibiotic showing the broad spectrum of antibacterial action. However, the use of this antibiotic is often connected with the risk of phototoxic reactions that lead to various skin disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26189561", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1034, "text": "The results obtained in vitro may explain the mechanisms of phototoxic reactions that occur in normal human epidermal melanocytes in vivo after exposure of skin to doxycycline and UVA radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26189561", "endSection": "abstract" }, { "offsetInBeginSection": 1948, "offsetInEndSection": 2119, "text": "Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17160610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "OBJECTIVES: Many patients undergoing long-term doxycycline treatment do not regularly take their treatment because of photosensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26299894", "endSection": "abstract" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1569, "text": "Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17160610", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 830, "text": "Thus, the action spectra of the drug photosensitivity patients were plotted and compared with those of 12 nonphotosensitive control patients: 10 patients were found to be photosensitive in the UVA range; the implicated drugs included quinine, sparfloxacin, amiodarone, doxycycline, mefenamic acid, nalidixic acid, fenbrufen, diclofenac, enalapril, diltiazem and prochlorperazine maleate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10233667", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 908, "text": "One patient on doxycycline was photosensitive in both the UVA and UVB ranges.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10233667", "endSection": "abstract" }, { "offsetInBeginSection": 1913, "offsetInEndSection": 2080, "text": "Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17160610", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1632, "text": "Anti-inflammatory-dose doxycycline should not be used by individuals with known hypersensitivity to tetracyclines or increased photosensitivity, or by pregnant or nursing women (anti-inflammatory-dose doxycycline is a pregnancy category-D medication).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17315050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "BACKGROUND: One of the most important dermatologic side effects of doxycycline is photosensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "One of the most important dermatologic side effects of doxycycline is photosensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291967", "endSection": "abstract" }, { "offsetInBeginSection": 1346, "offsetInEndSection": 1434, "text": "One patient experienced mild photosensitivity from doxycycline but continued to take it.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23182067", "endSection": "abstract" }, { "offsetInBeginSection": 1524, "offsetInEndSection": 1616, "text": "Participants in the doxycycline group had a higher incidence of nausea and photosensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15262663", "endSection": "abstract" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1499, "text": "Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17160610", "endSection": "abstract" } ] }, { "body": "What body process does the Dentate Gyrus Mossy Cell control?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28791347", "http://www.ncbi.nlm.nih.gov/pubmed/15986406", "http://www.ncbi.nlm.nih.gov/pubmed/28132828", "http://www.ncbi.nlm.nih.gov/pubmed/28132825", "http://www.ncbi.nlm.nih.gov/pubmed/16943315", "http://www.ncbi.nlm.nih.gov/pubmed/25583290" ], "ideal_answer": [ "Dentate gyrus mossy cells control spontaneous convulsive seizures and cognition" ], "exact_answer": [ "eplipsy and cognition" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D018891", "http://amigo.geneontology.org/amigo/term/GO:0044302" ], "type": "factoid", "id": "5a871b8d61bb38fb2400000a", "snippets": [ { "offsetInBeginSection": 1407, "offsetInEndSection": 1673, "text": "We propose that this aberrant activity-dependent intrinsic plasticity, which lastingly impairs the information processing of cortical inputs in dentate gyrus, may participate in hippocampal-related cognitive deficits, such as those reported in patients with epilepsy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583290", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 519, "text": "Within the hippocampal formation neuronal networks undergo major reorganization, including the sprouting of mossy fibers in the dentate gyrus; they establish aberrant recurrent synapses between dentate granule cells and operate via postsynaptic kainate receptors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583290", "endSection": "abstract" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1769, "text": "The results of the present study indicated the importance of hippocampal Zn/lipid metabolism\u2011associated genes in recurrent neonatal seizure\u2011induced aberrant mossy fiber sprouting, which may aid the identification of novel potential targets during epileptogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28791347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 725, "text": "Mossy cells in the hilus of the dentate gyrus constitute a major excitatory principal cell type in the mammalian hippocampus; however, it remains unknown how these cells behave in\u00a0vivo. Here, we have used two-photon Ca2+imaging to monitor the\u00a0activity of mossy cells in awake, behaving mice. We find that mossy cells are significantly more active than dentate granule cells in\u00a0vivo, exhibit spatial tuning during head-fixed spatial navigation, and undergo robust remapping of their spatial representations in response to contextual manipulation. Our\u00a0results provide a functional characterization of mossy cells in the behaving animal and demonstrate their active participation in spatial coding and contextual representation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28132825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Recent experimental and modeling results demonstrated that surviving mossy cells in the dentate gyrus play key roles in the generation of network hyperexcitability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16943315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Mossy cells give rise to the commissural and associational pathway of the dentate gyrus, and receive their major excitatory inputs from the mossy fibers of granule cells. Through these feed-back excitatory connections, mossy cells have been suggested to play important roles in both normal signal processing in learning and memory, as well as in seizure propagation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15986406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "Granule cells in the dentate gyrus of the hippocampus are thought to be essential to memory function by decorrelating overlapping input patterns (pattern separation). A second excitatory cell type in\u00a0the dentate gyrus, the mossy cell, forms an intricate circuit with granule cells, CA3c pyramidal cells, and\u00a0local interneurons, but the influence of mossy cells on dentate function is often overlooked.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28132828", "endSection": "abstract" } ] }, { "body": "Which ligament is most commonly injured in dashboard injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3425783", "http://www.ncbi.nlm.nih.gov/pubmed/20306414", "http://www.ncbi.nlm.nih.gov/pubmed/10623985" ], "ideal_answer": [ "Posterior cruciate ligament injuries have a reported incidence of between 3 and 37%, depending on the clinical setting. The most common mechanism of injury in motor vehicle accidents is a dashboard injury or direct force to the proximal anterior tibia." ], "exact_answer": [ "Posterior cruciate ligament" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D008022" ], "type": "factoid", "id": "5a6f98e6b750ff445500005d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Posterior cruciate ligament (PCL) injuries have a reported incidence of between 3 and 37%, depending on the clinical setting. The most common mechanism of injury in motor vehicle accidents is a dashboard injury or direct force to the proximal anterior tibia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10623985", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 575, "text": "Hyperflexion was the most common mechanism of injury, followed by pretibial trauma in the hyperflexed knee or in the \"dashboard\" injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3425783", "endSection": "abstract" } ] }, { "body": "What is the normal body temperature in dogs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25854787", "http://www.ncbi.nlm.nih.gov/pubmed/28992906" ], "ideal_answer": [ "According to the American Kennel Club (AKC), a temperature of 101 to 102.5 degrees Fahrenheit (38.3 to 39.2 degrees Celsius) is typical for dogs" ], "exact_answer": [ "101 to 102.5 degrees Fahrenheit or 38.3 to 39.2 degrees Celsius" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004285", "https://meshb.nlm.nih.gov/record/ui?ui=D001831" ], "type": "factoid", "id": "5a897a06fcd1d6a10c00000b", "snippets": [ { "offsetInBeginSection": 427, "offsetInEndSection": 491, "text": "Clinical examination revealed normal rectal temperature (38.3\u00b0C)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28992906", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 799, "text": "dian body temperature measured by the experienced investigator with the RDT and the NCIT were 38.3\u00b0C (range 35.5\u00b0C-41.1\u00b0C; 95% CI: 38.2-38.4\u00b0C) and 37.7\u00b0C (35.9\u00b0C-40.1\u00b0C; 95% CI: 37.7\u00b0C-37.9\u00b0C), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25854787", "endSection": "abstract" } ] }, { "body": "List symptoms of Heerfordt syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26885424", "http://www.ncbi.nlm.nih.gov/pubmed/12835855", "http://www.ncbi.nlm.nih.gov/pubmed/2307892", "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "http://www.ncbi.nlm.nih.gov/pubmed/15630597", "http://www.ncbi.nlm.nih.gov/pubmed/20184241", "http://www.ncbi.nlm.nih.gov/pubmed/21565911", "http://www.ncbi.nlm.nih.gov/pubmed/22565854", "http://www.ncbi.nlm.nih.gov/pubmed/12233082", "http://www.ncbi.nlm.nih.gov/pubmed/24082416", "http://www.ncbi.nlm.nih.gov/pubmed/25685372", "http://www.ncbi.nlm.nih.gov/pubmed/28079852", "http://www.ncbi.nlm.nih.gov/pubmed/17637529", "http://www.ncbi.nlm.nih.gov/pubmed/27549672", "http://www.ncbi.nlm.nih.gov/pubmed/23917502", "http://www.ncbi.nlm.nih.gov/pubmed/25087562", "http://www.ncbi.nlm.nih.gov/pubmed/23629431" ], "ideal_answer": [ "Heerfordt syndrome (also known as Heerfordt-Waldenstr\u00f6m or uveoparotid fever) is a rare presentation of sarcoidosis characterized by the presence of parotid gland enlargement, facial palsy, anterior uveitis, and fever." ], "exact_answer": [ [ "parotid gland enlargement" ], [ "facial palsy" ], [ "anterior uveitis" ], [ "fever" ] ], "type": "list", "id": "5a70d12899e2c3af26000001", "snippets": [ { "offsetInBeginSection": 1005, "offsetInEndSection": 1066, "text": "Case 3 showed Heerfordt syndrome with facial nerve paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28079852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Heerfordt's syndrome is defined as a combination of facial palsy, parotid swelling, uveitis and fever in sarcoidosis cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685372", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 346, "text": "Heerfordt-Waldenstr\u00f6m syndrome, a rare presentation of sarcoidosis, is characterized by the presence of parotid gland enlargement, facial palsy, anterior uveitis, and fever. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24082416", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1181, "text": "The patient was given a diagnosis of Heerfordt-Waldenstr\u00f6m syndrome, or uveoparotid fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24082416", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 538, "text": "Physical examination revealed right facial paralysis, parotid gland swelling, high fever and poor general condition. Ophthalmoscopy revealed anterior and posterior uveitis including macular edema and chorioretinal infiltrates. Angiography revealed a dense pattern of hyperfluorescent lesions and these observations resulted in the diagnosis of Heerfordt syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22565854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND: Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial nerve palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 317, "text": "Heerfordt's syndrome with uveitis, enlargement of the parotid glands and optional paralysis of the Nn. facialis is a form of sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15630597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The Heerfordt syndrome is characterized by fever, uveitis, swelling of parotid gland and facial nerve palsy, and 53 cases have been reported in Japan until 2000. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12233082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The Heerfordt syndrome is characterized by fever, uveitis, swelling of parotid gland and facial nerve palsy, and 53 cases have been reported in Japan until 2000.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12233082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Heerfordt syndrome is an unusual manifestation of systemic sarcoidosis and is characterized by parotitis, uveitis, and facial nerve paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2307892", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1029, "text": "Heerfordt syndrome is a rare manifestation of neurosarcoidosis and has to be included in the differential diagnosis of facial nerve palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial nerve palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Heerfordt syndrome with unilateral facial nerve palsy: a rare presentation of sarcoidosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "BACKGROUND: Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial nerve palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 449, "text": "We hereby present a case of Heerfordt syndrome with unilateral facial nerve palsy as a presentation of sarcoidosis.
HISTORY AND SIGNS: A 29-year-old male patient from Sri Lanka presented with eye redness OU, blurred vision OD, fever, headache, night sweat, fatigue, and weight loss (5 kg over 1 month).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1135, "text": "One year after onset of treatment, no recurrence was noted.
CONCLUSIONS: Heerfordt syndrome is a rare manifestation of neurosarcoidosis and has to be included in the differential diagnosis of facial nerve palsy.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Heerfordt's syndrome (HS) consists in its complete form of uveitis, parotid or salivary gland enlargement and cranial nerve palsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21565911", "endSection": "title" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1310, "text": "However, the otolaryngologist may encounter Heerfordt's syndrome as this syndrome presents with facial nerve palsy and swelling of the parotid gland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26885424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Heerfordt's syndrome is a rare manifestation of sarcoidosis characterized by the presence of facial nerve palsy, parotid gland enlargement, anterior uveitis, and low grade fever.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26885424", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "As a subtype of the clinical presentations associated with sarcoidosis, the combination of uveitis, parotid gland swelling, and facial nerve palsy is known as Heerfordt's syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23917502", "endSection": "title" }, { "offsetInBeginSection": 124, "offsetInEndSection": 185, "text": "Heerfordt's syndrome as a cause of facial palsy is very rare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Heerfordt's syndrome is a rare manifestation of sarcoidosis and is defined as a combination of facial palsy, parotid swelling, and uveitis, associated with a low-grade fever.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27549672", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Heerfordt's Syndrome Presenting with Recurrent Facial Nerve Palsy:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685372", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial nerve palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 244, "text": "We hereby present a case of Heerfordt syndrome with unilateral facial nerve palsy as a presentation of sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454397", "endSection": "abstract" } ] }, { "body": "In quadruped mammals, what bones make up the stifle?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26260666" ], "ideal_answer": [ "In quadruped mammals, the stifle is composed of 3 bones, the femur, the tibia and the patella." ], "exact_answer": [ [ "femur" ], [ "tibia" ], [ "patella" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D007867", "https://meshb.nlm.nih.gov/record/ui?ui=D013264" ], "type": "list", "id": "5a8afbf2fcd1d6a10c00001c", "snippets": [ { "offsetInBeginSection": 674, "offsetInEndSection": 931, "text": "MR images showed the bone, articular cartilage, menisci and ligaments of the normal tiger stifle. SE T1-weighted sequence provided excellent resolution of the subchondral bones of the femur, tibia and patella compared with the GE STIR T2-weighted MR images.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26260666", "endSection": "abstract" } ] }, { "body": "Are paralog genes co-regulated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28667373", "http://www.ncbi.nlm.nih.gov/pubmed/18493055", "http://www.ncbi.nlm.nih.gov/pubmed/20621981", "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "http://www.ncbi.nlm.nih.gov/pubmed/16860306", "http://www.ncbi.nlm.nih.gov/pubmed/20482863" ], "ideal_answer": [ "Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression.", "Co-regulation of paralog genes in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization.", "Co-regulation of paralog genes in the three-dimensional chromatin architecture. Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear.", "Co-regulation of paralog genes in the three-dimensional chromatin architecture. Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters.", "Yes. Paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization.", "yes", "Co-regulation of paralog genes in the three-dimensional chromatin architecture. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters." ], "exact_answer": "yes", "type": "yesno", "id": "5a6e21b4b750ff445500003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Co-regulation of paralog genes in the three-dimensional chromatin architecture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "endSection": "title" }, { "offsetInBeginSection": 164, "offsetInEndSection": 1452, "text": "Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters. These looping interactions can be measured by genome-wide chromatin conformation capture (Hi-C) experiments, which revealed self-interacting regions called topologically associating domains (TADs). We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs. To test this hypothesis, we integrated paralogy annotations with human gene expression data in diverse tissues, genome-wide enhancer-promoter associations and Hi-C experiments in human, mouse and dog genomes. We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. Combined, our results indicate that paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 713, "text": "We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1489, "text": "Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18493055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Analysis of the Drosophila melanogaster testes transcriptome reveals coordinate regulation of paralogous genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18493055", "endSection": "title" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1493, "text": "Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18493055", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 278, "text": "Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Co-regulation of paralog genes in the three-dimensional chromatin architecture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "endSection": "title" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1490, "text": "Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18493055", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1130, "text": "We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634932", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 494, "text": "MiRNA genes are often subject to co-evolutionary changes together with their target transcripts, which may be reflected by differences between paralog mouse and primate miRNA/mRNA pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28667373", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 626, "text": "We characterize the collapse over time through the distribution of runs of reduced paralog pairs in duplicated segments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20482863", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 869, "text": "In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20621981", "endSection": "abstract" }, { "offsetInBeginSection": 1254, "offsetInEndSection": 1410, "text": "We conclude that the similarity of hoxb3a/Hoxa3 regulatory mechanisms reflect the shared descent of both genes from a single ancestral paralog group 3 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16860306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16860306", "endSection": "title" }, { "offsetInBeginSection": 511, "offsetInEndSection": 839, "text": "By analyzing paralogs of testis-biased genes, we identified \"co-regulated\" paralogous pairs in which both genes are testis biased, \"anti-regulated\" pairs in which one paralog is testis biased and the other downregulated in testes, and \"neutral\" pairs in which one paralog is testis biased and the other constitutively expressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18493055", "endSection": "abstract" } ] }, { "body": "List 2 approved drug treatments for Inflammatory Bowel Disease (IBD).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28035201", "http://www.ncbi.nlm.nih.gov/pubmed/17547856", "http://www.ncbi.nlm.nih.gov/pubmed/26395529", "http://www.ncbi.nlm.nih.gov/pubmed/28597827", "http://www.ncbi.nlm.nih.gov/pubmed/28254463", "http://www.ncbi.nlm.nih.gov/pubmed/17129819", "http://www.ncbi.nlm.nih.gov/pubmed/25139379" ], "ideal_answer": [ "Patients with IBD, inflammtory Bowel Disease can be treated with steroids, or 2 approved biosimilar drugs infliximab (IFX) or adalimumab (ADA)" ], "exact_answer": [ [ "infliximab (IFX)" ], [ "adalimumab (ADA)" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D013812", "http://www.disease-ontology.org/api/metadata/DOID:0050589", "https://meshb.nlm.nih.gov/record/ui?ui=D015212" ], "type": "list", "id": "5a8dc6b4fcd1d6a10c000026", "snippets": [ { "offsetInBeginSection": 474, "offsetInEndSection": 595, "text": "Nonetheless, infliximab and adalimumab are the only biological agents that have been approved for this group of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28597827", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 673, "text": " In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25139379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 450, "text": "The introduction of infliximab into clinical practice is one of the most significant advances in the care of patients who have IBD. Infliximab has become an important part of the medical armamentarium to treat extraintestinal manifestations that often are refractory to other medications and are a significant cause of morbidity in these patients. Two other TNF inhibitors recently have demonstrated efficacy in CD: certolizumab pegol and adalimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17129819", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 449, "text": "Infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, is effective for induction and maintenance of remission of CD and UC. The role of infliximab for EIMs related to IBD has been less studied, but it is likely as effective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17547856", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 369, "text": "The Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28254463", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 373, "text": "lthough the TNF inhibitor infliximab is known to improve IBD outcomes in many different ways, several questions remain regarding the optimal way to employ this drug in the clinic, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26395529", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1016, "text": "Infliximab biosimilars for the treatment of IBD have been available in Europe and Asia for a few years and are expected to become available in the United States within the next 1 to 2 years", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035201", "endSection": "abstract" } ] }, { "body": "Which tool exists for microsatellite (SSR) loci detection and primer design?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27366148" ], "ideal_answer": [ "Microsatellites are genomic sequences comprised of tandem repeats of short nucleotide motifs widely used as molecular markers in population genetics. FullSSR is a new bioinformatic tool for microsatellite (SSR) loci detection and primer design using genomic data from NGS assay.", "FullSSR is a new bioinformatic tool for microsatellite (SSR) loci detection and primer design using genomic data from NGS assay. " ], "exact_answer": [ "FullSSR" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D018895", "https://meshb.nlm.nih.gov/record/ui?ui=D017931" ], "type": "factoid", "id": "5a6fa61ab750ff4455000060", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "FullSSR: Microsatellite Finder and Primer Designer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27366148", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Microsatellites are genomic sequences comprised of tandem repeats of short nucleotide motifs widely used as molecular markers in population genetics. FullSSR is a new bioinformatic tool for microsatellite (SSR) loci detection and primer design using genomic data from NGS assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27366148", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 278, "text": "FullSSR is a new bioinformatic tool for microsatellite (SSR) loci detection and primer design using genomic data from NGS assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27366148", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 926, "text": "FullSSR simplifies the detection of SSRs and primer design on a big data set.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27366148", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 927, "text": "FullSSR simplifies the detection of SSRs and primer design on a big data set.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27366148", "endSection": "abstract" } ] }, { "body": "Name curated data resources for ChIP-seq data", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24253304", "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "http://www.ncbi.nlm.nih.gov/pubmed/29069466", "http://www.ncbi.nlm.nih.gov/pubmed/22495751" ], "ideal_answer": [ "The MGA repository, Cistrome Data Browser and CR Cistrome are curated data resources for ChIP-seq data." ], "exact_answer": [ [ "MGA repository" ], [ "Cistrome Data Browser" ], [ "CR Cistrome" ], [ "CistromeMap" ] ], "type": "list", "id": "5a75dff883b0d9ea66000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "MGA repository: a curated data resource for ChIP-seq and other genome annotated data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069466", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "endSection": "title" }, { "offsetInBeginSection": 236, "offsetInEndSection": 1188, "text": "Although rapidly accumulating publicly available ChIP-seq, DNase-seq and ATAC-seq data are a valuable resource for the systematic investigation of gene regulation processes, a lack of standardized curation, quality control and analysis procedures have hindered extensive reuse of these data. To overcome this challenge, we built the Cistrome database, a collection of ChIP-seq and chromatin accessibility data (DNase-seq and ATAC-seq) published before January 1, 2016, including 13 366 human and 9953 mouse samples. All the data have been carefully curated and processed with a streamlined analysis pipeline and evaluated with comprehensive quality control metrics. We have also created a user-friendly web server for data query, exploration and visualization. The resulting Cistrome DB (Cistrome Data Browser), available online at http://cistrome.org/db, is expected to become a valuable resource for transcriptional and epigenetic regulation studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "CR Cistrome: a ChIP-Seq database for chromatin regulators and histone modification linkages in human and mouse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24253304", "endSection": "title" }, { "offsetInBeginSection": 134, "offsetInEndSection": 299, "text": "We have created CistromeMap as a web server to provide a comprehensive knowledgebase of all of the publicly available ChIP-Seq and DNase-Seq data in mouse and human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495751", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 751, "text": "To overcome this challenge, we built the Cistrome database, a collection of ChIP-seq and chromatin accessibility data (DNase-seq and ATAC-seq) published before January 1, 2016, including 13 366 human and 9953 mouse samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 283, "text": "We have created CistromeMap as a web server to provide a comprehensive knowledgebase of all of the publicly available ChIP-Seq and DNase-Seq data in mouse and human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495751", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1192, "text": "The resulting Cistrome DB (Cistrome Data Browser), available online at http://cistrome.org/db, is expected to become a valuable resource for transcriptional and epigenetic regulation studies.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "endSection": "title" } ] }, { "body": "Treatment of which disease was studied in the Gore REDUCE Clinical Study?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29090661", "http://www.ncbi.nlm.nih.gov/pubmed/28902580" ], "ideal_answer": [ "The Gore REDUCE Clinical Study studied superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke." ], "exact_answer": [ "patent foramen ovale" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D013812", "https://meshb.nlm.nih.gov/record/ui?ui=D000068397" ], "type": "factoid", "id": "5a72302b2dc08e987e000005", "snippets": [ { "offsetInBeginSection": 2058, "offsetInEndSection": 2502, "text": "CONCLUSIONS: Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation. (Funded by W.L. Gore and Associates; Gore REDUCE ClinicalTrials.gov number, NCT00738894 .).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28902580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29090661", "endSection": "title" }, { "offsetInBeginSection": 194, "offsetInEndSection": 508, "text": "Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29090661", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 507, "text": "Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29090661", "endSection": "abstract" } ] }, { "body": "Which comparisons demonstrate the applicability of StereoGene in regulatory genomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028265" ], "ideal_answer": [ "StereoGene rapidly estimates genome-wide correlation among pairs of genomic features. These features may represent high-throughput data mapped to reference genome or sets of genomic annotations in that reference genome. StereoGene enables correlation of continuous data directly, avoiding the data binarization and subsequent data loss. Correlations are computed among neighboring genomic positions using kernel correlation. Representing the correlation as a function of the genome position, StereoGene outputs the local correlation track as part of the analysis. StereoGene also accounts for confounders such as input DNA by partial correlation. Numerous comparisons of ChIP-Seq datasets from the Human Epigenome Atlas and FANTOM CAGE demonstrate the wide applicability of StereoGene in regulatory genomics." ], "exact_answer": [ [ "Comparisons of ChIP-Seq datasets from the Human Epigenome Atlas" ], [ "Comparisons of ChIP-Seq datasets from FANTOM CAGE" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D023281" ], "type": "list", "id": "5a760e5583b0d9ea66000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "StereoGene: rapid estimation of genome-wide correlation of continuous or interval feature data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028265", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1570, "text": "Genomics features with similar genome-wide distributions are generally hypothesized to be functionally related, for example, colocalization of histones and transcription start sites indicate chromatin regulation of transcription factor activity. Therefore, statistical algorithms to perform spatial, genome-wide correlation among genomic features are required.Results: Here, we propose a method, StereoGene, that rapidly estimates genome-wide correlation among pairs of genomic features. These features may represent high-throughput data mapped to reference genome or sets of genomic annotations in that reference genome. StereoGene enables correlation of continuous data directly, avoiding the data binarization and subsequent data loss. Correlations are computed among neighboring genomic positions using kernel correlation. Representing the correlation as a function of the genome position, StereoGene outputs the local correlation track as part of the analysis. StereoGene also accounts for confounders such as input DNA by partial correlation. We apply our method to numerous comparisons of ChIP-Seq datasets from the Human Epigenome Atlas and FANTOM CAGE to demonstrate its wide applicability. We observe the changes in the correlation between epigenomic features across developmental trajectories of several tissue types consistent with known biology and find a novel spatial correlation of CAGE clusters with donor splice sites and with poly(A) sites. These analyses provide examples for the broad applicability of StereoGene for regulatory genomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028265", "endSection": "abstract" } ] }, { "body": "What is the aim of the 4D nucleome project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28905911" ], "ideal_answer": [ "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions.", "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. ", "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions.The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions.Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.", "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.", "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. " ], "type": "summary", "id": "5a6f940bb750ff445500005a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 692, "text": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905911", "endSection": "abstract" } ] }, { "body": "List symptoms of the Zieve's syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2355237", "http://www.ncbi.nlm.nih.gov/pubmed/11761804", "http://www.ncbi.nlm.nih.gov/pubmed/8819039", "http://www.ncbi.nlm.nih.gov/pubmed/1122928", "http://www.ncbi.nlm.nih.gov/pubmed/464793", "http://www.ncbi.nlm.nih.gov/pubmed/2208946", "http://www.ncbi.nlm.nih.gov/pubmed/26203455", "http://www.ncbi.nlm.nih.gov/pubmed/12430042", "http://www.ncbi.nlm.nih.gov/pubmed/871409", "http://www.ncbi.nlm.nih.gov/pubmed/1217221", "http://www.ncbi.nlm.nih.gov/pubmed/24748143", "http://www.ncbi.nlm.nih.gov/pubmed/2716993", "http://www.ncbi.nlm.nih.gov/pubmed/966632", "http://www.ncbi.nlm.nih.gov/pubmed/7110955" ], "ideal_answer": [ "Zieve's syndrome, characterized by jaundice, hyperlipidaemia and haemolytic anaemia. It usually develops in young, chronically alcoholic subjects with enlarged fatty liver. It may rarely occur with intracranial haemorrhage." ], "exact_answer": [ [ "jaundice" ], [ "hyperlipidaemia" ], [ "haemolytic anaemia" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D012816" ], "type": "list", "id": "5a75ee7e83b0d9ea66000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Hemolysis in Acute Alcoholic Hepatitis: Zieve's Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26203455", "endSection": "title" }, { "offsetInBeginSection": 176, "offsetInEndSection": 316, "text": "Lab studies revealed hemolysis as the cause of anemia. The patient was diagnosed with Zieve's syndrome and managed with supportive measures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26203455", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 383, "text": "After exclusion of other possibilities, Zieve's syndrome was diagnosed. This is a condition of hyperbilirubinaemia, Coombs' negative haemolytic anaemia and hyperlipidaemia associated with alcoholism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24748143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "We report a case of recurrent Zieve's syndrome, consisting of jaundice, hemolytic anemia and hyperlipoproteinemia, initiated by alcohol abuse. The crucial feature of this syndrome, which allows differentiation with common acute alcoholic hepatitis, is the presence of hemolysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11761804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Zieve's syndrome consists of transient haemolytic anaemic, jaundice, hyperlipidaemia and alcohol-induced liver disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8819039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Zieve's syndrome (hyperlipidaemia, anaemia and fatty liver degeneration) may rarely occur with intracranial haemorrhage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2355237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Alcohol-associated haemolysis in Zieve's syndrome: a clinical and laboratory study of five cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2208946", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "In 1958 Zieve described a syndrome of jaundice, hyperlipidaemia, and transient haemolytic anaemia associated with alcohol abuse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2208946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Zieve's syndrome, characterized by jaundice, hyperlipaemia and haemolytic anaemia, usually develops in young, chronically alcoholic subjects with enlarged fatty liver. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7110955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Zieve's syndrome (ZS), which consists of transient haemolytic anaemia, jaundice, hyperlipoproteinaemia, and alcohol-induced liver disease, was studied in male patients during the acute (n = 20) and the remittent (n = 10) phase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/871409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Red cell metabolic and membrane features in haemolytic anaemia of alcoholic liver disease (Zieve's syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/871409", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "[Changes of erythrocyte membrane lipids in ethanol induced hyperlipidemia (Zieve's syndrome) (author's transl)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/966632", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "In 11 patients with alcohol-induced hyperlipemia, of whom 6 showed a Zieve Syndrome increased phospholipids, triglycerides and total cholesterol were found in the red cells stromal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/966632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The macroscopic and microscopic findings of a case of Zieve's syndrome are described (fatty liver, icterus, hyperlipemia and hemolytic anemia in chronic alcoholism). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1217221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Reversible haemolytic anaemia associated with decreased red cell half-life and reticulocytosis was studied in 10 patients with Zieve's syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1122928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The Zieve's syndrome consists of the transient association of cholestatic jaundice, hemolytic anemia, hyperlipemia, in a chronic alcoholic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/464793", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 485, "text": "Laboratory findings revealed Zieve-syndrome (alcoholic hyperlipemia, hemolytic anemia, and alcoholic fatty liver) and negative Hounsfield Unit measurement of the hypodense rim finally identified it as a layer of fat around the clot.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2716993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The Zieve syndrome is characterized by hemolytic anemia in conjunction with secondary hyperlipidemia in patients suffering from alcohol-related toxic liver damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12430042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Zieve's syndrome, characterized by jaundice, hyperlipaemia and haemolytic anaemia, usually develops in young, chronically alcoholic subjects with enlarged fatty liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7110955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The Zieve's syndrome consists of the transient association of cholestatic jaundice, hemolytic anemia, hyperlipemia, in a chronic alcoholic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/464793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "We report a case of recurrent Zieve's syndrome, consisting of jaundice, hemolytic anemia and hyperlipoproteinemia, initiated by alcohol abuse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11761804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The macroscopic and microscopic findings of a case of Zieve's syndrome are described (fatty liver, icterus, hyperlipemia and hemolytic anemia in chronic alcoholism).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1217221", "endSection": "abstract" } ] }, { "body": "What is the link between psoriatic arthritis and depression", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22556134", "http://www.ncbi.nlm.nih.gov/pubmed/25161652", "http://www.ncbi.nlm.nih.gov/pubmed/28212760", "http://www.ncbi.nlm.nih.gov/pubmed/24692521", "http://www.ncbi.nlm.nih.gov/pubmed/28052180", "http://www.ncbi.nlm.nih.gov/pubmed/26178281", "http://www.ncbi.nlm.nih.gov/pubmed/28237512", "http://www.ncbi.nlm.nih.gov/pubmed/26882216", "http://www.ncbi.nlm.nih.gov/pubmed/21794775", "http://www.ncbi.nlm.nih.gov/pubmed/26186277", "http://www.ncbi.nlm.nih.gov/pubmed/28733473", "http://www.ncbi.nlm.nih.gov/pubmed/24800325", "http://www.ncbi.nlm.nih.gov/pubmed/22015150", "http://www.ncbi.nlm.nih.gov/pubmed/21317853", "http://www.ncbi.nlm.nih.gov/pubmed/27221798" ], "ideal_answer": [ "Depression Is Associated with an Increased Risk of Psoriatic Arthritis among Patients with Psoriasis. ", "Psoriasis is a common chronic inflammatory disease which is associated with extensive comorbidities, including psoriatic arthritis. " ], "exact_answer": [ "comorbidity" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:9008", "https://meshb.nlm.nih.gov/record/ui?ui=D015535" ], "type": "factoid", "id": "5a8712af61bb38fb24000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Depression Is Associated with an Increased Risk of Psoriatic Arthritis among Patients with Psoriasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28237512", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 438, "text": "merging data also suggest associations between psoriasis and other comorbidities beyond psoriatic arthritis, including chronic kidney disease, inflammatory bowel disease, hepatic disease, certain malignancies, infections, and mood disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28212760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28733473", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "To investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28733473", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1392, "text": "Rate of depression was higher in patients with PsA compared to non-PsA patients. The rate of suicidal behaviors was similar between the two cohorts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26882216", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 378, "text": "Over the past decade, multiple studies have shown that not only is there an association between psoriasis and psoriatic arthritis, depression, and substance abuse, but psoriasis patients also have a higher incidence of obesity, diabetes, heart disease and stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21317853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "Psoriasis is a chronic disease that affects more than the skin. It has an impact on every facet of an individual's life and is associated with numerous comorbidities, such as obesity, diabetes, cardiovascular disease, psoriatic arthritis, metabolic syndrome, squamous cell carcinoma, lymphoma, depression, anxiety and other immune-related conditions, such as Crohn's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24800325", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1522, "text": "We found an increased risk of depression in US women with psoriasis compared with those without psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26186277", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 823, "text": "The impact of comorbidities (psoriatic arthritis, cardiovascular disease, diabetes, and depression) on relative importance scores of each attribute was assessed by analyses of varianc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22015150", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 383, "text": "Furthermore, obesity and psychological diseases such as depression and anxiety disorders are linked with psoriasis and play a\u00a0central role in its management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27221798", "endSection": "abstract" }, { "offsetInBeginSection": 1455, "offsetInEndSection": 1895, "text": " Recommendations were synthesized into 19 final recommendations ranging mainly from grade C to D, and relating to a large spectrum of comorbidities observed in clinical practice: CVD, obesity, osteoporosis, depression, infections, and cancer. Level of agreement ranged from 80.9% to 95.8%.CONCLUSION: These practical evidence-based recommendations can guide management of comorbidities in patients with RA, PsA, and PsO and optimize outcome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26178281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Anxiety and depressive symptoms and illness perceptions in psoriatic arthritis and associations with physical health-related quality of life.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22556134", "endSection": "title" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1734, "text": " The rate of depression and anxiety is significantly higher in patients with PsA than in those with PsC. Depression and anxiety are associated with disease-related factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24692521", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1600, "text": "The prevalence of anxiety symptoms and the prevalence of depression symptoms are high among patients suffering psoriatic arthritis in the studied population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21794775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "Psoriasis (Pso) is a common chronic cutaneous inflammatory disease involving the skin that is associated with serious comorbidities. Comorbidities in Pso include psoriatic arthritis (PsA), reduced quality of life, malignancy, depression, but also a constellation of associated conditions that enhance the cardiovascular (CV) risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25161652", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1314, "text": "Dermatologists and primary care providers share roles in screening for associated comorbidities (including cardiovascular disorders, chronic kidney disease, Crohn disease, dyslipidemia, diabetes mellitus/insulin resistance, depression, metabolic syndrome, obesity, and psoriatic arthritis),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28052180", "endSection": "abstract" } ] }, { "body": "Is polyadenylation a process that stabilizes a protein by adding a string of Adenosine residues to the end of the molecule?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27940037", "http://www.ncbi.nlm.nih.gov/pubmed/19479986", "http://www.ncbi.nlm.nih.gov/pubmed/23776204", "http://www.ncbi.nlm.nih.gov/pubmed/16282984", "http://www.ncbi.nlm.nih.gov/pubmed/22400011", "http://www.ncbi.nlm.nih.gov/pubmed/9020972", "http://www.ncbi.nlm.nih.gov/pubmed/23989958", "http://www.ncbi.nlm.nih.gov/pubmed/1684936", "http://www.ncbi.nlm.nih.gov/pubmed/16467265", "http://www.ncbi.nlm.nih.gov/pubmed/9223284", "http://www.ncbi.nlm.nih.gov/pubmed/9733864", "http://www.ncbi.nlm.nih.gov/pubmed/26730730", "http://www.ncbi.nlm.nih.gov/pubmed/19576221", "http://www.ncbi.nlm.nih.gov/pubmed/18177749", "http://www.ncbi.nlm.nih.gov/pubmed/28537233", "http://www.ncbi.nlm.nih.gov/pubmed/9933592", "http://www.ncbi.nlm.nih.gov/pubmed/9611233", "http://www.ncbi.nlm.nih.gov/pubmed/3037325", "http://www.ncbi.nlm.nih.gov/pubmed/2579655", "http://www.ncbi.nlm.nih.gov/pubmed/11557765", "http://www.ncbi.nlm.nih.gov/pubmed/9242905", "http://www.ncbi.nlm.nih.gov/pubmed/17267594", "http://www.ncbi.nlm.nih.gov/pubmed/8440247", "http://www.ncbi.nlm.nih.gov/pubmed/16738135", "http://www.ncbi.nlm.nih.gov/pubmed/12601000" ], "ideal_answer": [ "No, polyadenylation is a process that stabilizes mRNA by adding up to 200 adenosine residues to the 3' end of the trabscript" ], "exact_answer": "no", "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0043631", "https://meshb.nlm.nih.gov/record/ui?ui=D026723" ], "type": "yesno", "id": "5a8714e261bb38fb24000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The addition of poly(A) tails to eukaryotic nuclear mRNAs promotes their stability, export to the cytoplasm and translation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23989958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Most eukaryotic genes express mRNAs with alternative polyadenylation sites at their 3' ends", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23776204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Polyadenylation is the non-template addition of adenosine nucleotides at the 3'-end of RNA, which occurs after transcription and generates a poly(A) tail up to 250-300 nucleotides long.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28537233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Polyadenylation is a process of endonucleolytic cleavage of the mRNA, followed by addition of up to 250 adenosine residues to the 3' end of the mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16467265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Plant mitochondrial polyadenylated mRNAs are degraded by a 3'- to 5'-exoribonuclease activity, which proceeds unimpeded by stable secondary structures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11557765", "endSection": "title" }, { "offsetInBeginSection": 478, "offsetInEndSection": 770, "text": "We show that a 3'- to 5'-exoribonuclease activity is responsible for the preferential degradation of polyadenylated mRNAs as compared with non-polyadenylated mRNAs, and that 20-30 adenosine residues constitute the optimal poly(A) tail size for inducing degradation of RNA substrates in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11557765", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 748, "text": "The diversity of polyadenylation sites suggests that mRNA polyadenylation in prokaryotes is a relatively indiscriminate process that can occur at all mRNA's 3'-ends and does not require specific consensus sequences as in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9242905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Polyadenylation of premessenger RNAs occurs posttranscriptionally in the nucleus of eukaryotic cells by cleavage of the precursor and polymerization of adenosine residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9223284", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1186, "text": "However, under certain conditions, poly(A) tracts may lead to mRNA stabilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9242905", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1219, "text": "From these results, we propose that in plant mitochondria, poly(A) tails added at the 3' ends of mRNAs promote an efficient 3'- to 5'- degradation process..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11557765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9611233", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 622, "text": "Transcription in these cells is polycistronic. Tens to hundreds of protein-coding genes of unrelated function are arrayed in long clusters on the same DNA strand. Polycistrons are cotranscriptionally processed by trans-splicing at the 5' end and polyadenylation at the 3' end, generating monocistronic units ready for degradation or translation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17267594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "We have devised a simple chromatographic procedure which isolates five polyadenylation factors that are required for polyadenylation of eukaryotic mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1684936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "During mammalian oocyte maturation, protein synthesis is mainly controlled through cytoplasmic polyadenylation of stored maternal mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19479986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Identification and characterization of a polyadenylated small RNA (s-poly A+ RNA) in dinoflagellates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2579655", "endSection": "title" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1058, "text": "Thus, polyadenylation seems to be a major component of the RNA editing machinery that affects overlapping genes in animal mitochondria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9020972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Pre-mRNA 3'-end processing, the process through which almost all eukaryotic mRNAs acquire a poly(A) tail is generally inhibited during the cellular DNA damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Almost all eukaryotic mRNAs possess 3' ends with a polyadenylate (poly(A)) tail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22400011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "We previously demonstrated, by limited mutagenesis, that conserved sequence elements within the 5' end of influenza virus virion RNA (vRNA) are required for the polyadenylation of mRNA in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9733864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Polyadenylation of mRNA precursors by poly(A) polymerase depends on two specificity factors and their recognition sequences", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8440247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and polyadenylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Formation of mRNA 3' termini involves cleavage of an mRNA precursor and polyadenylation of the newly formed end. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3037325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The polyadenylation of RNA is a near-universal feature of RNA metabolism in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26730730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The mechanism of RNA degradation in Escherichia coli involves endonucleolytic cleavage, polyadenylation of the cleavage product by poly(A) polymerase, and exonucleolytic degradation by the exoribonucleases, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12601000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "The addition of poly(A)-tails to RNA is a process common to almost all organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16738135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The addition of poly(A) tails to RNA is a phenomenon common to all organisms examined so far. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16282984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The addition of poly(A)-tails to RNA is a phenomenon common to almost all organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18177749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Polyadenylation contributes to the destabilization of bacterial mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9933592", "endSection": "abstract" } ] }, { "body": "Which cancers compose Carney's triad?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22664948", "http://www.ncbi.nlm.nih.gov/pubmed/8272014", "http://www.ncbi.nlm.nih.gov/pubmed/16142610", "http://www.ncbi.nlm.nih.gov/pubmed/22968735", "http://www.ncbi.nlm.nih.gov/pubmed/18018644", "http://www.ncbi.nlm.nih.gov/pubmed/3827356", "http://www.ncbi.nlm.nih.gov/pubmed/24867050", "http://www.ncbi.nlm.nih.gov/pubmed/19089668", "http://www.ncbi.nlm.nih.gov/pubmed/11878780", "http://www.ncbi.nlm.nih.gov/pubmed/1620943", "http://www.ncbi.nlm.nih.gov/pubmed/8091266", "http://www.ncbi.nlm.nih.gov/pubmed/16308708", "http://www.ncbi.nlm.nih.gov/pubmed/12893072", "http://www.ncbi.nlm.nih.gov/pubmed/24840526", "http://www.ncbi.nlm.nih.gov/pubmed/19561114", "http://www.ncbi.nlm.nih.gov/pubmed/10468897", "http://www.ncbi.nlm.nih.gov/pubmed/3361958", "http://www.ncbi.nlm.nih.gov/pubmed/12149713", "http://www.ncbi.nlm.nih.gov/pubmed/16229813", "http://www.ncbi.nlm.nih.gov/pubmed/16555728", "http://www.ncbi.nlm.nih.gov/pubmed/17706515" ], "ideal_answer": [ "Carney's triad is a rare pathogenic entity which consists of 3 rare soft tissue tumors: gastric leiomyosarcoma, pulmonary chondroma and extraadrenal paraganglioma. It is usually diagnosed in young women. The presence of three tumors at the same time is not required for its diagnosis (incomplete Carney's Triad)." ], "exact_answer": [ [ "gastric leiomyosarcoma" ], [ "pulmonary chondroma" ], [ "extraadrenal paraganglioma" ] ], "type": "list", "id": "5a75df9883b0d9ea66000002", "snippets": [ { "offsetInBeginSection": 601, "offsetInEndSection": 680, "text": "New adrenal tumors have also been associated with nonhereditary Carney's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24840526", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 517, "text": "Carney designated the combination of 3 rare soft tissue tumors (gastric leiomyosarcoma, pulmonary chondroma, and extraadrenal paraganglioma) as a syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24867050", "endSection": "abstract" }, { "offsetInBeginSection": 2063, "offsetInEndSection": 2166, "text": "In sporadic Carney's triad additional pulmonary chondromas are observed and there are no SDH mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "A case of bilateral multiple pulmonary chondroma: necessity of follow-up for Carney's triad.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664948", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "We report a case of pulmonary bilateral multiple chondromas that were possibly an initial clinical presentation of Carney's triad. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664948", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 842, "text": "These chondromas were possibly components of Carney's triad, because each nodule had a thin fibrous pseudocapsule and did not have an entrapped epithelium and fat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "A curious association of three rare tumours was described by Carney in 1977. 'Carney's triad' characteristically includes multifocal pulmonary chondroma, gastric stromal sarcoma and extra-adrenal paraganglioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "We report a female teenager who presented with a gastrointestinal stromal tumor of the stomach and a paraganglioneuroma. She later developed a pulmonary chondroma, fulfilling the requirements of Carney's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17706515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "A 34-year-old man, who had undergone the gastrectomy for gastrointestinal stromal tumor (GIST) and para-aortic paraganglioma 3 years before, was found to have a left lung tumor on a computed tomography. The tumor was revealed to be a pulmonary hamartoma, and diagnosed as Carney's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18018644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "INTRODUCTION: Carney's triad is a rare pathogenic entity which consists of the association in young women of multiple condromatosis in the lung, gastric leiomyosarcoma, and extradrenal paraganglioma; although the presence of three at the same time is not required for its diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19089668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Interstitial cell of Cajal (ICC) hyperplasia has been documented in conditions associated with multiple gastrointestinal stromal tumours (GISTs) (familial GIST syndromes, Carney's triad and von Recklinghausen's disease) and rarely in the vicinity of sporadic GISTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16308708", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 314, "text": "Multiple gastric tumors and pararenal non functioning paraganglioma were found. No chondromas were detected. An incomplete Carney's Triad was diagnosed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16555728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Gastrointestinal stromal tumours (GIST) occur mostly as sporadic solitary lesions involving the tubular GI tract and are only rarely associated with other benign or malignant neoplasms or occur as part of a multi-neoplastic disease as in the setting of Carney's triad and von Recklinghausen's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16142610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Carney's triad is a very unusual syndrome, associating three different tumours on the same patient, a young woman generally: a gastric leiomyoblastoma, a pulmonary chondroma and an extra-adrenal paraganglioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16229813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "This report encourages clinicians to consider a diagnosis of Carney's triad in patients with multifocal gastric stromal sarcoma, extraadrenal paraganglioma (predominantly mediastinal), or pulmonary chondroma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11878780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Carney's triad represents the association of gastric gastrointestinal stromal tumor, pulmonary chondroma, and extraadrenal paraganglioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12149713", "endSection": "abstract" }, { "offsetInBeginSection": 638, "offsetInEndSection": 787, "text": "Thus, the Triad may be a disorder of the autonomic nervous system rather than a multiple endocrine neoplasia syndrome or multiple hamartoma syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3827356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Carney's triad is a syndrome of unknown etiology, representing a combination of gastrointestinal stromal tumors, bronchial chondromas and vagal, adrenal or paraadrenal paragangliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12893072", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 303, "text": "Two of the Carney's triad components-the paragangliomas and the gastrointestinal stromal tumors-are potentially lethal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12893072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Carney's triad, a rare disorder affecting young females, is characterized by the presence of at least two of the three following neoplasms: gastric epithelioid leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary chondroma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8091266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Carney's triad--gastric leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma--is a syndrome that occurs primarily in young women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3361958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "We communicate a case with the Carney triad (gastric leiomyosarcoma, pulmonary chondromatosis and extra-adrenal paraganglioma).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1620943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The etiology of the Carney's triad (gastrointestinal stromal tumors, pulmonary chondromas, and paragangliomas) is unknown, and only 57 cases have been reported since its identification in 1977.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10468897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Carney's triad is defined by the coexistence of at least two of three rare disorders, including gastric epithelioid leiomyosarcoma (malignant leiomyoblastoma), pulmonary chondroma, and paraganglioma, most often extra-adrenal and functioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8272014", "endSection": "abstract" } ] }, { "body": "What is the preDIVA clinical trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28263374", "http://www.ncbi.nlm.nih.gov/pubmed/28596452", "http://www.ncbi.nlm.nih.gov/pubmed/27474376", "http://www.ncbi.nlm.nih.gov/pubmed/19812459" ], "ideal_answer": [ "The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years." ], "exact_answer": [ "Prevention of Dementia by Intensive Vascular Care" ], "type": "factoid", "id": "5a9dad764e03427e73000007", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 291, "text": "To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28263374", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 435, "text": "The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28596452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27474376", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Prevention of dementia by intensive vascular care (PreDIVA): a cluster-randomized trial in progress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19812459", "endSection": "title" } ] }, { "body": "What effect does azeliragon have on RAGE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27678025" ], "ideal_answer": [ "Azeliragon is an inhibitor of receptor for advanced glycation end products (RAGE)." ], "exact_answer": [ "Inhibitory" ], "type": "factoid", "id": "5a9d29571d1251d03b000018", "snippets": [ { "offsetInBeginSection": 531, "offsetInEndSection": 901, "text": "Expert opinion: Drugs in Phase III clinical development for AD include one inhibitor of the \u03b2-secretase cleaving enzyme (BACE) (verubecestat), three anti-A\u03b2 monoclonal antibodies (solanezumab, gantenerumab, and aducanumab), an inhibitor of receptor for advanced glycation end products (RAGE) (azeliragon) and the combination of cromolyn sodium and ibuprofen (ALZT-OP1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27678025", "endSection": "abstract" } ] }, { "body": "What is the drug forxiga used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23170914", "http://www.ncbi.nlm.nih.gov/pubmed/28383856", "http://www.ncbi.nlm.nih.gov/pubmed/24030968", "http://www.ncbi.nlm.nih.gov/pubmed/25389049", "http://www.ncbi.nlm.nih.gov/pubmed/25402624", "http://www.ncbi.nlm.nih.gov/pubmed/25418019" ], "ideal_answer": [ "Dapagliflozin (Forxiga\u00ae) is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes." ], "exact_answer": [ "Treatment of patients with type 2 diabetes." ], "type": "factoid", "id": "5a9e2386de7cb99d40000004", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 103, "text": "Dapagliflozin (forxiga\u00ae) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28383856", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 164, "text": "Dapagliflozin (DAPA) (Farxiga or Forxiga) is a sodium glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes mellitus(T2DM) treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25418019", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 742, "text": "Dapagliflozin (Forxiga) belongs to a new class of oral glucose-lowering drugs that inhibit renal glucose reabsorption and promote glycosuria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24030968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Dapagliflozin (Forxiga\u00ae) is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23170914", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 623, "text": "antidiabetic drug Forxiga (dapagliflozin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25402624", "endSection": "abstract" } ] }, { "body": "What is the most common feature of the Doege\u2013Potter syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25636632", "http://www.ncbi.nlm.nih.gov/pubmed/27376978", "http://www.ncbi.nlm.nih.gov/pubmed/23302323", "http://www.ncbi.nlm.nih.gov/pubmed/28784156", "http://www.ncbi.nlm.nih.gov/pubmed/27932370", "http://www.ncbi.nlm.nih.gov/pubmed/28523334", "http://www.ncbi.nlm.nih.gov/pubmed/28228892", "http://www.ncbi.nlm.nih.gov/pubmed/28109372", "http://www.ncbi.nlm.nih.gov/pubmed/22206790", "http://www.ncbi.nlm.nih.gov/pubmed/28410845" ], "ideal_answer": [ "Doege-Potter syndrome is a paraneoplastic syndrome characterized by hypoglycemia secondary to a solitary fibrous tumor of the pleura." ], "exact_answer": [ "hypoglycemia" ], "type": "factoid", "id": "5a761ac3aacfb9cd4c000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "We describe a patient with Doege-Potter syndrome (solitary fibrous tumor of the pleura presenting with hypoglycemia) and illustrate several important lessons learned from the case. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28109372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Solitary fibrous tumour of the pleura (SFTP) is a rare primary tumour of the pleura associated with 4% of cases with a paraneoplastic hypoglycaemia, termed Doege-Potter syndrome (DPS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27932370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege-Potter syndrome).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28228892", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Doege-Potter syndrome\u00a0is a paraneoplastic\u00a0syndrome\u00a0characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28410845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "AIM: Doege-Potter syndrome is a rare condition consisting of a mesenchymal tumor, either benign or malignant, accompanied by severe hypoglycemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28523334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Large pleural tumor revealed by severe hypoglycemia: Doege-Potter syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28523334", "endSection": "title" }, { "offsetInBeginSection": 270, "offsetInEndSection": 377, "text": "f hypoglycemia is associated with a solitary fibrous tumor, it is referred to as the Doege-Potter syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28784156", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1018, "text": "Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23302323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "INTRODUCTION: Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23302323", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 614, "text": "We present a case of Doege-Potter syndrome whose interest is to consider the TFSP as a cause of hypoglycemia in patients with pleural tumors.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22206790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Syndrome Doege-Potter is a paraneoplastic syndrome in which hypoglycemia is the result of tumors producing insulin growth factor-like (IGF-II) it is most often solitary fibrous tumor of the pleura (TFSP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22206790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "A common problem in the elderly with an uncommon cause: hypoglycaemia secondary to the Doege-Potter syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636632", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23302323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Doege-Potter syndrome is a paraneoplastic syndrome characterized by tumor-associated hypoglycemia secondary to a solitary fibrous tumor of the pleura.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27376978", "endSection": "abstract" } ] }, { "body": "Milwaukee protocol was tested for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24708671", "http://www.ncbi.nlm.nih.gov/pubmed/19263274", "http://www.ncbi.nlm.nih.gov/pubmed/26639059", "http://www.ncbi.nlm.nih.gov/pubmed/18305449", "http://www.ncbi.nlm.nih.gov/pubmed/28559126", "http://www.ncbi.nlm.nih.gov/pubmed/25156675", "http://www.ncbi.nlm.nih.gov/pubmed/27730539" ], "ideal_answer": [ "The Milwaukee protocol was tested for treatment of rabies. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. The Milwaukee Protocol has proved to be ineffective for rabies and should no longer be used." ], "exact_answer": [ "rabies" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D013812", "https://meshb.nlm.nih.gov/record/ui?ui=D004194" ], "type": "factoid", "id": "5a679e8cb750ff4455000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Caring for a patient with rabies: implications of the Milwaukee protocol for infection control and public health measures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28559126", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 434, "text": "The Milwaukee protocol, which to date has five reported human rabies survivors associated with its use, has been suggested as a potential management pathway for human rabies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28559126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26639059", "endSection": "title" }, { "offsetInBeginSection": 384, "offsetInEndSection": 649, "text": "Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. None of these therapies can be substantiated in rabies or other forms of acute viral encephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26639059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26639059", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 872, "text": "Rabies is virtually always fatal after clinical disease develops, and there have only been rare survivors. The Milwaukee protocol, which includes therapeutic coma, has been shown to be ineffective and should no longer be used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27730539", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 275, "text": "The Milwaukee Protocol has proved to be ineffective for rabies and should no longer be used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25156675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26639059", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 403, "text": "This report summarizes the clinical course of disease in that patient, who was treated using the Milwaukee Protocol, an experimental treatment protocol similar to one used for the rabies survivor described in 2005.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18305449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "In this first report of rabies in Equatorial Guinea, problems accompanying the application of the Milwaukee Protocol are described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19263274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "BACKGROUND Human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the Milwaukee Protocol for intensive care management has recently been employed, with limited success in improving survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24708671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Applying the Milwaukee protocol to treat canine rabies in Equatorial Guinea.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19263274", "endSection": "title" } ] }, { "body": "Are stress granules membraneous?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28377462", "http://www.ncbi.nlm.nih.gov/pubmed/27838525", "http://www.ncbi.nlm.nih.gov/pubmed/23279909", "http://www.ncbi.nlm.nih.gov/pubmed/28306503" ], "ideal_answer": [ "Stress granules (SG) are membrane-less compartments involved in regulating mRNAs during stress." ], "exact_answer": "no", "type": "yesno", "id": "5aa825b1fcf4565872000003", "snippets": [ { "offsetInBeginSection": 540, "offsetInEndSection": 700, "text": "PMLOs are different in size, shape, and composition, and almost invariantly contain intrinsically disordered proteins (e.g., eIF4B and TDP43 in stress granules,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27838525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in the formation of multiple membrane-less organelles involved in RNA metabolism, including stress granules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28306503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Stress granules (SG) are membrane-less compartments involved in regulating mRNAs during stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28377462", "endSection": "abstract" }, { "offsetInBeginSection": 38, "offsetInEndSection": 211, "text": " In addition to membrane delimited organelles, proteins and RNAs can organize themselves into specific domains. Some examples include stress granules and subnuclear bodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23279909", "endSection": "abstract" } ] }, { "body": "When is 16S rRNA Gene Sequencing used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28207855", "http://www.ncbi.nlm.nih.gov/pubmed/28103917", "http://www.ncbi.nlm.nih.gov/pubmed/27984802", "http://www.ncbi.nlm.nih.gov/pubmed/29107843" ], "ideal_answer": [ "Taxonomic characterization is performed by genotypic approaches such as 16S rRNA gene sequencing." ], "type": "summary", "id": "5aa4f47cd6d6b54f7900000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "The different pipelines that may be used in 16S rRNA gene profiling of bacterial communities are known to have a significant impact on alpha and beta diversity measures and this may prevent direct comparison of results obtained in studies using different bioinformatic approaches to analyse raw sequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29107843", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 332, "text": " Metataxonomics tools analyze high-throughput sequencing data, primarily from 16S rRNA gene sequencing and DNAseq, to identify microorganisms and viruses within a complex mixture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28103917", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1167, "text": "Two biological methods were used, Ribosomal Intergenic Spacer Analysis (RISA), and 16S rRNA gene sequencing with Illumina Miseq, to evaluate the discriminating power of soil bacterial communities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27984802", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 685, "text": "The aim of this study was to assess the integration of different approaches, genotypic (16S rRNA gene sequencing), proteomic (MALDI-TOF MS) and metabolomic (1H-NMR), for the taxonomic and metabolic characterization of Lactobacillus species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28207855", "endSection": "abstract" } ] }, { "body": "What does intepirdine target?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28253832" ], "ideal_answer": [ "Intepiridine is a 5-HT6 antagonist." ], "exact_answer": [ "5-HT6" ], "type": "factoid", "id": "5a9ac7ba1d1251d03b000013", "snippets": [ { "offsetInBeginSection": 551, "offsetInEndSection": 725, "text": "The 5-HT-6 receptor antagonists Idalopirdine and Intepirdine have shown the most progress in current clinical trials and warrant consideration as emerging treatments for AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253832", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 1077, "text": "This review discusses 5-HT6 antagonists currently in clinical trials as potential treatments for AD symptomatology and how 5-HT6 physiology may play a positive role in alleviating AD symptom pathophysiology. A literature search using PubMed was conducted using the terms Idalopirdine, Intepirdine, 5-HT-6 antagonist, and AD as keywords. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253832", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1399, "text": "If current Phase-3 trials are positive, 5-HT6 antagonists such as Idalopirdine and Intepirdine may be considered as supplementary treatments to ChEI's and NMDA receptor antagonists for the symptomatic treatment of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253832", "endSection": "abstract" } ] }, { "body": "Is the consumption of chocolate associated with an increase in cardiovascular disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26936339", "http://www.ncbi.nlm.nih.gov/pubmed/26983749", "http://www.ncbi.nlm.nih.gov/pubmed/27493901", "http://www.ncbi.nlm.nih.gov/pubmed/29141542", "http://www.ncbi.nlm.nih.gov/pubmed/27164919", "http://www.ncbi.nlm.nih.gov/pubmed/28356040", "http://www.ncbi.nlm.nih.gov/pubmed/28824916", "http://www.ncbi.nlm.nih.gov/pubmed/22169919", "http://www.ncbi.nlm.nih.gov/pubmed/18827977", "http://www.ncbi.nlm.nih.gov/pubmed/20858571", "http://www.ncbi.nlm.nih.gov/pubmed/28324761", "http://www.ncbi.nlm.nih.gov/pubmed/28649567", "http://www.ncbi.nlm.nih.gov/pubmed/21666964", "http://www.ncbi.nlm.nih.gov/pubmed/22653982", "http://www.ncbi.nlm.nih.gov/pubmed/24274771", "http://www.ncbi.nlm.nih.gov/pubmed/27088635", "http://www.ncbi.nlm.nih.gov/pubmed/11790962" ], "ideal_answer": [ "The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke.", "Chocolate consumption can reduce cardio-cerebrovascular risk." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1287", "https://meshb.nlm.nih.gov/record/ui?ui=D000069956", "https://meshb.nlm.nih.gov/record/ui?ui=D002318", "https://meshb.nlm.nih.gov/record/ui?ui=D002099" ], "type": "yesno", "id": "5aa304f1d6d6b54f79000004", "snippets": [ { "offsetInBeginSection": 82, "offsetInEndSection": 244, "text": "The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28824916", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 269, "text": "chocolate has been shown to decrease CVD risk due to its antioxidant and anti-inflammatory properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28649567", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 528, "text": "A number of studies have shown that dietary polyphenols exert a protective effect against hypertension, dyslipidemias, inflammation, endothelial function and atherosclerosis, conditions associated with increased risk for cardiovascular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28356040", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 97, "text": "Chocolate consumption may have a beneficial effect on cardiovascular health,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28324761", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 665, "text": "Data currently available indicate that daily consumption of cocoa-rich chocolate (rich in polyphenols) may at least partially lower cardiovascular disease risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21666964", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1500, "text": "CONCLUSIONS The blood pressure and cholesterol lowering effects of dark chocolate consumption are beneficial in the prevention of cardiovascular events in a population with metabolic syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22653982", "endSection": "abstract" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1610, "text": "Daily dark chocolate consumption could be an effective cardiovascular preventive strategy in this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22653982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "BACKGROUND The consumption of chocolate and cocoa has established cardiovascular benefits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493901", "endSection": "abstract" }, { "offsetInBeginSection": 1586, "offsetInEndSection": 1684, "text": "CONCLUSIONS Chocolate consumption is associated with lower risk of MI and ischaemic heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26936339", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1019, "text": "Chocolate consumption was inversely associated with MI risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26936339", "endSection": "abstract" }, { "offsetInBeginSection": 1538, "offsetInEndSection": 1625, "text": "Chocolate consumption is associated with lower risk of MI and ischaemic heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26936339", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 504, "text": "The consumption of cocoa/ chocolate (i) increases plasma antioxidant capacity, (ii) diminishes platelet function and inflammation, and (iii) decreases diastolic and systolic arterial pressures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21666964", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 975, "text": "Chocolate consumption was inversely associated with MI risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26936339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Chocolate consumption is inversely associated with prevalent coronary heart disease: the National Heart, Lung, and Blood Institute Family Heart Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20858571", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26983749", "endSection": "title" }, { "offsetInBeginSection": 1523, "offsetInEndSection": 1624, "text": "Collectively, the antioxidant effects of flavonoid-rich foods may reduce cardiovascular disease risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11790962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24274771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "It has been shown that the consumption of cocoa has a positive influence on a number of cardiovascular surrogate parameters such as arterial vasodilatation and a moderate decrease in blood pressure in humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22169919", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1554, "text": "This study has shown that increasing the polyphenol content of the diet via consumption of F&V, berries and dark chocolate results in a significant improvement in an established marker of cardiovascular risk in hypertensive participants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27164919", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 143, "text": "Cocoa flavonoids exert cardiovascular benefits and neuroprotection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27088635", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 136, "text": "Accumulating evidence suggests potential preventive effects of chocolate/cocoa on the risk of cardio vascular disease (CVD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29141542", "endSection": "abstract" } ] }, { "body": "What is the association of circular RNA to breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28484086", "http://www.ncbi.nlm.nih.gov/pubmed/27829232" ], "ideal_answer": [ "circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs. circRNA frequency may be a marker for cell proliferation in breast cancer." ], "type": "summary", "id": "5a9924ea1d1251d03b000008", "snippets": [ { "offsetInBeginSection": 497, "offsetInEndSection": 837, "text": "Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28484086", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1303, "text": "The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28484086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Circular RNAs and their associations with breast cancer subtypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27829232", "endSection": "title" }, { "offsetInBeginSection": 795, "offsetInEndSection": 1390, "text": "Notably, circRNA results reveal that normal-adjacent tissues in estrogen receptor positive (ER+) subtype have relatively higher numbers of circRNAs than tumor samples in TCGA. Similar phenomenon of high circRNA numbers were observed in normal breast-mammary tissues from the Genotype-Tissue Expression (GTEx) project. Finally, we observed that number of circRNAs in normal-adjacent samples of ER+ subtype is inversely correlated to the risk-of-relapse proliferation (ROR-P) score for proliferating genes, suggesting that circRNA frequency may be a marker for cell proliferation in breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27829232", "endSection": "abstract" }, { "offsetInBeginSection": 1484, "offsetInEndSection": 1630, "text": "We believe that Circ-Seq will be a valuable tool to identify circRNAs useful in the diagnosis and treatment of other cancers and complex diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27829232", "endSection": "abstract" } ] }, { "body": "List 3 symptoms of Wernicke encephalopathy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17698536", "http://www.ncbi.nlm.nih.gov/pubmed/25856744", "http://www.ncbi.nlm.nih.gov/pubmed/27988455", "http://www.ncbi.nlm.nih.gov/pubmed/25550705", "http://www.ncbi.nlm.nih.gov/pubmed/22869492", "http://www.ncbi.nlm.nih.gov/pubmed/26869612", "http://www.ncbi.nlm.nih.gov/pubmed/23935638", "http://www.ncbi.nlm.nih.gov/pubmed/27300674", "http://www.ncbi.nlm.nih.gov/pubmed/28289649", "http://www.ncbi.nlm.nih.gov/pubmed/14644703", "http://www.ncbi.nlm.nih.gov/pubmed/16219837" ], "ideal_answer": [ "Wernicke's encephalopathy (WE) is a neurological syndrome caused by thiamine deficiency, and clinically characterized by ophthalmoplegia, ataxia and acute confusion.", "Wernicke's encephalopathy (WE) is a neurological syndrome caused by thiamine deficiency, and clinically characterized by ophthalmoplegia, ataxia and acute confusion. " ], "exact_answer": [ [ "ophthalmoplegia" ], [ "ataxia" ], [ "acute confusion" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014899", "http://www.disease-ontology.org/api/metadata/DOID:2384" ], "type": "list", "id": "5a981bcffcd1d6a10c00002d", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 180, "text": "Wernicke's encephalopathy (WE) is a neurological syndrome caused by thiamine deficiency, and clinically characterized by ophthalmoplegia, ataxia and acute confusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27988455", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 629, "text": "entire triad of classic features of Wernicke-Korsakoff syndrome: confusion, ataxia, and ophthalmoplegia or nystagmus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27300674", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 174, "text": "Wernicke encephalopathy (WE) is a medical emergency caused by thiamine deficiency, characterized by cerebellar ataxia, ophthalmoplegia, and cognitive disturbances", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26869612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Wernicke encephalopathy is an acute neuropsychiatric disease with heterogeneous symptoms, including changes in mental status, ataxia and ocular abnormalities; if left untreated, these symptoms can lead to morbidity and even to mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25856744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25550705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Wernicke's encephalopathy is an acute neurolopsychiatric syndrome caused by thiamine deficiency, and classically presents with the triad of opthalmopathy, ataxia and altered mentality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22869492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Wernicke's encephalopathy is a serious neurologic disorder caused by vitamin-B1 or thiamine deficiency. The classical triad of clinical symptoms described by Wernicke (gait ataxia, ophthalmoplegia, and confusion) are found in only a third of patients upon initial examination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14644703", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 147, "text": "Wernicke's encephalopathy is a well-described syndrome characterized by the classic triad of confusion, ataxia, and ophthalmoplegia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23935638", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 212, "text": "Wernicke encephalopathy is a severe neurologic disorder that results from a dietary vitamin B1 deficiency. It is characterized by changes in consciousness, ocular abnormalities, and ataxia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17698536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Wernicke encephalopathy (WE) is a neurologic disorder characterized by clinical symptoms, such as nystagmus, ataxia, and mental confusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28289649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Wernicke encephalopathy is a neurologic disorder that results from thiamine deficiency. It is associated with a classic triad of symptoms consisting of ataxia, ocular motor cranial neuropathies, and changes in consciousness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16219837", "endSection": "abstract" } ] }, { "body": "Describe RIblast", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28459942" ], "ideal_answer": [ "LncRNAs play important roles in various biological processes. Although more than 58\u2009000 human lncRNA genes have been discovered, most known lncRNAs are still poorly characterized. One approach to understanding the functions of lncRNAs is the detection of the interacting RNA target of each lncRNA. Because experimental detections of comprehensive lncRNA-RNA interactions are difficult, computational prediction of lncRNA-RNA interactions is an indispensable technique. However, the high computational costs of existing RNA-RNA interaction prediction tools prevent their application to large-scale lncRNA datasets. 'RIblast' is an ultrafast RNA-RNA interaction prediction method based on the seed-and-extension approach. RIblast discovers seed regions using suffix arrays and subsequently extends seed regions based on an RNA secondary structure energy model. Computational experiments indicate that RIblast achieves a level of prediction accuracy similar to those of existing programs, but at speeds over 64 times faster than existing programs." ], "type": "summary", "id": "5a763b679e632bc066000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "RIblast: an ultrafast RNA-RNA interaction prediction system based on a seed-and-extension approach.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1079, "text": "LncRNAs play important roles in various biological processes. Although more than 58\u2009000 human lncRNA genes have been discovered, most known lncRNAs are still poorly characterized. One approach to understanding the functions of lncRNAs is the detection of the interacting RNA target of each lncRNA. Because experimental detections of comprehensive lncRNA-RNA interactions are difficult, computational prediction of lncRNA-RNA interactions is an indispensable technique. However, the high computational costs of existing RNA-RNA interaction prediction tools prevent their application to large-scale lncRNA datasets.Results: Here, we present 'RIblast', an ultrafast RNA-RNA interaction prediction method based on the seed-and-extension approach. RIblast discovers seed regions using suffix arrays and subsequently extends seed regions based on an RNA secondary structure energy model. Computational experiments indicate that RIblast achieves a level of prediction accuracy similar to those of existing programs, but at speeds over 64 times faster than existing programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 772, "text": "However, the high computational costs of existing RNA-RNA interaction prediction tools prevent their application to large-scale lncRNA datasets.
Results: Here, we present 'RIblast', an ultrafast RNA-RNA interaction prediction method based on the seed-and-extension approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 911, "text": "RIblast discovers seed regions using suffix arrays and subsequently extends seed regions based on an RNA secondary structure energy model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 896, "text": "RIblast discovers seed regions using suffix arrays and subsequently extends seed regions based on an RNA secondary structure energy model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 757, "text": "Results Here, we present 'RIblast', an ultrafast RNA-RNA interaction prediction method based on the seed-and-extension approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "RIblast: an ultrafast RNA-RNA interaction prediction system based on a seed-and-extension approach.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "title" }, { "offsetInBeginSection": 735, "offsetInEndSection": 873, "text": "RIblast discovers seed regions using suffix arrays and subsequently extends seed regions based on an RNA secondary structure energy model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459942", "endSection": "abstract" } ] }, { "body": "What is Alzheimers disease resilience?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27358062", "http://www.ncbi.nlm.nih.gov/pubmed/28921611", "http://www.ncbi.nlm.nih.gov/pubmed/28025282", "http://www.ncbi.nlm.nih.gov/pubmed/27815399" ], "ideal_answer": [ "Some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia." ], "type": "summary", "id": "5a9d7caa1d1251d03b00001e", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 243, "text": "Apolipoprotein E (APOE) \u025b4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28025282", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 384, "text": "some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28921611", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 927, "text": "Participants with normal cognition (n = 297) and mild cognitive impairment (n = 432) were drawn from the Alzheimer's Disease Neuroimaging Initiative. Resilience metrics were defined at baseline by examining the residuals when regressing brain aging outcomes (hippocampal volume and cognition) on CSF biomarkers. A positive residual reflected better outcomes than expected for a given level of pathology (high resilience). Residuals were integrated into a latent variable model of resilience and validated by testing their ability to independently predict diagnostic conversion, cognitive decline, and the rate of ventricular dilation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27815399", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 463, "text": "Alzheimer's disease (AD) represents the most common form of dementia in elder populations with approximately 30 million cases worldwide. Genome wide genotyping and sequencing studies have identified many genetic variants associated with late-onset Alzheimer's disease (LOAD). While most of these variants are associated with increased risk of developing LOAD, only limited number of reports focused on variants that are protective against the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27358062", "endSection": "abstract" } ] }, { "body": "Which R package has been developed for analyzing Non-invasive prenatal testing (NIPT) data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24990604" ], "ideal_answer": [ "Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex. RAPIDR has been extensively tested with a large sample set as part of the RAPID project in the UK. The package contains quality control steps to make it robust for use in the clinical setting.", "RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex." ], "exact_answer": [ "RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package)" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D011296" ], "type": "factoid", "id": "5a8b27e6fcd1d6a10c00001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 686, "text": "Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex. RAPIDR has been extensively tested with a large sample set as part of the RAPID project in the UK. The package contains quality control steps to make it robust for use in the clinical setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 314, "text": "RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 306, "text": "RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 295, "text": "RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "endSection": "title" } ] }, { "body": "Is the gene CDKN2A nevogenic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15304099", "http://www.ncbi.nlm.nih.gov/pubmed/28830827", "http://www.ncbi.nlm.nih.gov/pubmed/475444", "http://www.ncbi.nlm.nih.gov/pubmed/12406345", "http://www.ncbi.nlm.nih.gov/pubmed/10620111" ], "ideal_answer": [ "Yes, CDKN2A is nevogenic" ], "exact_answer": "yes", "type": "yesno", "id": "5a9d79ca1d1251d03b00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28830827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Phenotypic characteristics of members of a melanoma prone kindred with a V126D CDKN2A gene mutation were monitored over approximately 15 y.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15304099", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 559, "text": " Rare germline mutations in CDKN2A predispose to melanoma and appear to be nevogenic, although the correlation between nevus phenotype and mutation status is poor. It is plausible that more common CDKN2A variants may influence both melanoma susceptibility and nevus susceptibility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12406345", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 651, "text": "supporting the view that CDKN2A is nevogenic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10620111", "endSection": "abstract" } ] }, { "body": "Are there ways of joint Bayesian inference of risk variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27407109" ], "ideal_answer": [ "Yes. RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) is a Bayesian model for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001499", "https://meshb.nlm.nih.gov/record/ui?ui=D014644" ], "type": "yesno", "id": "5a80dbaafaa1ab7d2e000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27407109", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1444, "text": "Genome wide association studies (GWAS) provide a powerful approach for uncovering disease-associated variants in human, but fine-mapping the causal variants remains a challenge. This is partly remedied by prioritization of disease-associated variants that overlap GWAS-enriched epigenomic annotations. Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations. In simulation, RiVIERA promising power in detecting causal variants and causal annotations, the multi-trait joint inference further improved the detection power. We applied RiVIERA to model the existing GWAS summary statistics of 9 autoimmune diseases and Schizophrenia by jointly harnessing the potential causal enrichments among 848 tissue-specific epigenomics annotations from ENCODE/Roadmap consortium covering 127 cell/tissue types and 8 major epigenomic marks. RiVIERA identified meaningful tissue-specific enrichments for enhancer regions defined by H3K4me1 and H3K27ac for Blood T-Cell specifically in the nine autoimmune diseases and Brain-specific enhancer activities exclusively in Schizophrenia. Moreover, the variants from the 95% credible sets exhibited high conservation and enrichments for GTEx whole-blood eQTLs located within transcription-factor-binding-sites and DNA-hypersensitive-sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27407109", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 535, "text": "Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27407109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27407109", "endSection": "title" } ] }, { "body": "Describe Achenbach\u2019s syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26774542", "http://www.ncbi.nlm.nih.gov/pubmed/12162986", "http://www.ncbi.nlm.nih.gov/pubmed/26669687", "http://www.ncbi.nlm.nih.gov/pubmed/24021741", "http://www.ncbi.nlm.nih.gov/pubmed/2373612" ], "ideal_answer": [ "Achenbach\u2019s syndrome is Paroxysmal finger haematoma. It is benign condition resulting in the sudden appearance of bruising on one or more fingers, either spontaneously or after minimal trauma, and resolving without treatment.It can be differentiated from other pathologies by clinical spectrum, patient demographics and in doubtful circumstances (acute limb ischemia) by Doppler sonography." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:6687" ], "type": "summary", "id": "5a733efc2dc08e987e000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "BACKGROUND: Paroxysmal finger haematoma (also known as \"Achenbach syndrome\") is a benign condition resulting in the sudden appearance of bruising on one or more fingers, either spontaneously or after minimal trauma, and resolving without treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26774542", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1033, "text": "DISCUSSION: In the absence of known aetiologies and/or treatments for spontaneous paroxysmal finger haematomas, a knowledge of this rare condition can at least help doctors reassure their patients by diagnosing their condition and pointing out the benign nature thereof. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26774542", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 1022, "text": "It presents with unilateral volar discoloration of a finger (100\u00a0%). It is associated with pain (n\u00a0=\u00a07/12, 58.\u00a0%), edema (n\u00a0=\u00a07/12, 58\u00a0%), and paresthesia (n\u00a0=\u00a03/12, 25\u00a0%). The median time to resolution of symptoms without any intervention was 4\u00a0days (range 2-14).CONCLUSION: AS is self-limiting and a non-urgent surgical condition. It can be differentiated from other pathologies by clinical spectrum, patient demographics and in doubtful circumstances (acute limb ischemia) by Doppler sonography. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26669687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "[Paroxysmal finger hematoma (Achenbach syndrome)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2373612", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Paroxysmal haematoma of the fingers (Achenbach's syndrome) is a rarely reported entity. It often occurs spontaneously or subsequent to minor injuries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2373612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "[Paroxysmal finger hematoma (Achenbach syndrome)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2373612", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Paroxysmal finger haematomas (Achenbach's syndrome) with angiographic abnormalities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12162986", "endSection": "title" } ] }, { "body": "Has intepirdine been evaluated in clinical trials? (November 2017)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28720101" ], "ideal_answer": [ "Yes, intepirdine was in Phase III clinical trials in November 2017." ], "exact_answer": "yes", "type": "yesno", "id": "5a9acba61d1251d03b000014", "snippets": [ { "offsetInBeginSection": 1569, "offsetInEndSection": 1786, "text": "Using small molecules blocking 5-HT6serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28720101", "endSection": "abstract" } ] }, { "body": "Is subacute sclerosing panencephalitis caused by the Measles vaccine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28750182", "http://www.ncbi.nlm.nih.gov/pubmed/26765654", "http://www.ncbi.nlm.nih.gov/pubmed/28116334", "http://www.ncbi.nlm.nih.gov/pubmed/21311432", "http://www.ncbi.nlm.nih.gov/pubmed/15464644", "http://www.ncbi.nlm.nih.gov/pubmed/26587021", "http://www.ncbi.nlm.nih.gov/pubmed/15384893", "http://www.ncbi.nlm.nih.gov/pubmed/29062617", "http://www.ncbi.nlm.nih.gov/pubmed/23188587", "http://www.ncbi.nlm.nih.gov/pubmed/2019970", "http://www.ncbi.nlm.nih.gov/pubmed/27777245", "http://www.ncbi.nlm.nih.gov/pubmed/25761293", "http://www.ncbi.nlm.nih.gov/pubmed/29112137", "http://www.ncbi.nlm.nih.gov/pubmed/1468866", "http://www.ncbi.nlm.nih.gov/pubmed/6685828", "http://www.ncbi.nlm.nih.gov/pubmed/15566859", "http://www.ncbi.nlm.nih.gov/pubmed/2807674", "http://www.ncbi.nlm.nih.gov/pubmed/15246492", "http://www.ncbi.nlm.nih.gov/pubmed/21245918", "http://www.ncbi.nlm.nih.gov/pubmed/2774513", "http://www.ncbi.nlm.nih.gov/pubmed/6879001", "http://www.ncbi.nlm.nih.gov/pubmed/18037676", "http://www.ncbi.nlm.nih.gov/pubmed/22408143", "http://www.ncbi.nlm.nih.gov/pubmed/27634625", "http://www.ncbi.nlm.nih.gov/pubmed/25802788", "http://www.ncbi.nlm.nih.gov/pubmed/11545478", "http://www.ncbi.nlm.nih.gov/pubmed/28387784", "http://www.ncbi.nlm.nih.gov/pubmed/15557053" ], "ideal_answer": [ "Subacute sclerosing panencephalitis is caused by the Measles and can be prevented by the measles vaccine.", "Subacute sclerosing panencephalitis (SSPE) is a potentially fatal complication of measles. " ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D008458", "http://www.disease-ontology.org/api/metadata/DOID:8970", "https://meshb.nlm.nih.gov/record/ui?ui=D013344", "https://meshb.nlm.nih.gov/record/ui?ui=D022542", "https://meshb.nlm.nih.gov/record/ui?ui=D008457" ], "type": "yesno", "id": "5aa3fa73d6d6b54f79000008", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 103, "text": "Subacute sclerosing panencephalitis (SSPE) is a potentially fatal complication of measles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116334", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 155, "text": "Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles. We reviewed California cases from 1998-2015 to understand risk f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28387784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Subacute sclerosing panencephalitis should be eliminated by measles vaccination", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28750182", "endSection": "title" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1102, "text": "The mean interval between measles infection and onset of subacute sclerosing panencephalitis was 6.5 years (range = 3-11 years).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15246492", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1429, "text": "Active surveillance of subacute sclerosing panencephalitis for those with measles infection during the 1988 outbreak is necessary to conduct multicenter drug trials for this devastating disease.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15246492", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1230, "text": "There has been an increasing trend of subacute sclerosing panencephalitis in southern China after the measles outbreak in 1988.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15246492", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 532, "text": "The prevalence rate of subacute sclerosing panencephalitis in Hong Kong and Macau in 2002 was 1 per million total population or 5.5 per million children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15246492", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 825, "text": "Because a positive correlation was found between the prevalence of measles and the onset of subacute sclerosing panencephalitis, particularly among children infected at an early age, it is vital to eradicate measles infection by vaccination.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22408143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Incidence of subacute sclerosing panencephalitis following measles and measles vaccination in Japan.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2807674", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "UNLABELLED Subacute sclerosing panencephalitis (SSPE), in the majority of cases, is caused by the wild measles virus, although there are some reports relating SSPE to vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15384893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease caused by the measles (rubeola) virus and is most often seen in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2019970", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 888, "text": "There was no indication that measles vaccine can induce SSPE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6685828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26587021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence caused by persistent defective measles virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21311432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25802788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Subacute sclerosing panencephalitis (SSPE) caused by persistent defective measles virus strains, is a progressive neurological disorder of children and adolescents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23188587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Subacute sclerosing panencephalitis (SSPE), in the majority of cases, is caused by the wild measles virus, although there are some reports relating SSPE to vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15384893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Measles can persist in the central nervous system and cause subacute sclerosing panencephalitis (SSPE), a progressive disease that is almost always fatal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6879001", "endSection": "abstract" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1198, "text": "However, because of the median 8-year interval between measles and onset of SSPE,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1468866", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1261, "text": "The prevention of endemic circulation of measles virus in England and Wales through the high coverage achieved with MMR vaccine, together with the measles/rubella vaccination campaign of 1994, has resulted in the near elimination of SSPE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15557053", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 1276, "text": "We applied the polymerase chain reaction (PCR) to detect the measles virus genome in specimens from a 12-year-old boy with SSPE who had received measles vaccine 10 years before and had no history of apparent natural measles. The oligonucleotide primers for PCR were prepared based on the nucleotide sequence of the F and NP genes of the measles virus Edmonston strain.RESULTS: F and NP genes were detected in both the cerebrospinal fluid and peripheral blood lymphocytes. Nucleotide and deduced amino acid sequence analysis of the F gene showed that the patient's virus was different from that of the vaccine strain. Judging from these results, it was likely that the SSPE-associated strain in this case was derived from the wild-type rather than the vaccine strain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15566859", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 125, "text": "subacute sclerosing panencephalitis (SSPE) is a late, rare and usually fatal complication of measles infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21245918", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 130, "text": "Subacute sclerosing panencephalitis (SSPE) is a chronic central nervous (CNS) system infection caused by measles virus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11545478", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1832, "text": " Epidemiological and virological data suggest that measles vaccine does not cause SSPE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18037676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Subacute sclerosing panencephalitis, a rare, progressive, fatal central nervous system disease of children, is caused by measles virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2774513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Subacute sclerosing panencephalitis is a form of chronic persistent measles encephalitis in childhood which rarely manifests after wild virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15464644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27777245", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 144, "text": "Subacute sclerosing panencephalitis (SSPE) is a fatal encephalitis manifesting a number of years after a primary measles infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25761293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "In 2015, the Oregon Health Authority was notified of the death of a boy with subacute sclerosing panencephalitis (SSPE), a rare and fatal complication of measles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26765654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Subacute Sclerosing Panencephalitis (SSPE) is a debilitating disorder associated with the measles infection in childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29062617", "endSection": "abstract" } ] }, { "body": "What is host induced gene silencing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28967180" ], "ideal_answer": [ "Host-induced gene silencing (HIGS) is a transgenic technology used to silence fungal genes in planta during attempted infection and thereby reduces disease levels. HIGS relies on the host plant's ability to produce mobile small interfering RNA molecules, generated from long double-stranded RNA, which are complementary to targeted fungal genes. These molecules are transferred from the plant to invading fungi via an uncharacterised mechanism, to cause gene silencing." ], "type": "summary", "id": "5aa38f75d6d6b54f79000005", "snippets": [ { "offsetInBeginSection": 634, "offsetInEndSection": 1104, "text": "Host-induced gene silencing (HIGS) is a transgenic technology used to silence fungal genes in planta during attempted infection and thereby reduces disease levels. HIGS relies on the host plant's ability to produce mobile small interfering RNA molecules, generated from long double-stranded RNA, which are complementary to targeted fungal genes. These molecules are transferred from the plant to invading fungi via an uncharacterised mechanism, to cause gene silencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967180", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1347, "text": "We then discuss the developments and implications of combining HIGS with other methods of disease control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967180", "endSection": "abstract" } ] }, { "body": "What is maternal spindle transfer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28092013" ], "ideal_answer": [ "Maternal spindle transfer (MST) is a cutting edge germline-altering, IVF-based embryonic technique used to prevent the maternal transmission of serious mitochondrial diseases." ], "type": "summary", "id": "5a9929ed1d1251d03b000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "In October 2015 the UK enacted legislation to permit the clinical use of two cutting edge germline-altering, IVF-based embryonic techniques: pronuclear transfer and maternal spindle transfer (PNT and MST). The aim is to use these techniques to prevent the maternal transmission of serious mitochondrial diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28092013", "endSection": "abstract" } ] }, { "body": "Does armodafinil improve fatigue of glioma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26902850" ], "ideal_answer": [ "No. Eight week course of armodafinil did not improve fatigue or quality of life in glioma patients undergoing radiotherapy. However, this conclusion is based on one identified clinical trial." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D005221", "https://meshb.nlm.nih.gov/record/ui?ui=D010361", "http://www.biosemantics.org/jochem#4216693", "https://meshb.nlm.nih.gov/record/ui?ui=D005910" ], "type": "yesno", "id": "5a76072283b0d9ea66000013", "snippets": [ { "offsetInBeginSection": 1316, "offsetInEndSection": 1482, "text": "CONCLUSIONS: While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902850", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 236, "text": "We evaluated whether armodafinil, a wakefulness-promoting medication, improves fatigue in glioma patients undergoing RT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902850", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1254, "text": "Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale, FACT-G, CFS, or BFI. Further analysis suggests no difference between the arms even after accounting for the potential bias of missing data. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902850", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1521, "text": "Treatment was well tolerated with few grade 3 or 4 toxicities.
CONCLUSIONS: While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902850", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1163, "text": "Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale, FACT-G, CFS, or BFI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902850", "endSection": "abstract" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1441, "text": "While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902850", "endSection": "abstract" } ] }, { "body": "What is the role of tankyrases in response to Double Strand Breaks (DSBs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26845027" ], "ideal_answer": [ "Tankyrases promote homologous recombination and check point activation in response to DSBs." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D038501", "https://meshb.nlm.nih.gov/record/ui?ui=D053903", "https://meshb.nlm.nih.gov/record/ui?ui=D053960", "http://amigo.geneontology.org/amigo/term/GO:1901291", "http://amigo.geneontology.org/amigo/term/GO:1990166" ], "type": "summary", "id": "5a775182faa1ab7d2e000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26845027", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26845027", "endSection": "title" } ] }, { "body": "Which molecules are inhibited by anticancer drug Dovitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26149476", "http://www.ncbi.nlm.nih.gov/pubmed/29101463", "http://www.ncbi.nlm.nih.gov/pubmed/28183331", "http://www.ncbi.nlm.nih.gov/pubmed/25683141", "http://www.ncbi.nlm.nih.gov/pubmed/27267856", "http://www.ncbi.nlm.nih.gov/pubmed/27082062", "http://www.ncbi.nlm.nih.gov/pubmed/28213002", "http://www.ncbi.nlm.nih.gov/pubmed/28714017", "http://www.ncbi.nlm.nih.gov/pubmed/23443805", "http://www.ncbi.nlm.nih.gov/pubmed/23908597", "http://www.ncbi.nlm.nih.gov/pubmed/26723100", "http://www.ncbi.nlm.nih.gov/pubmed/22180308", "http://www.ncbi.nlm.nih.gov/pubmed/28736761", "http://www.ncbi.nlm.nih.gov/pubmed/27705940", "http://www.ncbi.nlm.nih.gov/pubmed/23041231", "http://www.ncbi.nlm.nih.gov/pubmed/27216979", "http://www.ncbi.nlm.nih.gov/pubmed/27315356", "http://www.ncbi.nlm.nih.gov/pubmed/27245147", "http://www.ncbi.nlm.nih.gov/pubmed/28377480", "http://www.ncbi.nlm.nih.gov/pubmed/27100354", "http://www.ncbi.nlm.nih.gov/pubmed/27025387", "http://www.ncbi.nlm.nih.gov/pubmed/28342996" ], "ideal_answer": [ "Dovitinib (TKI-258/CHIR-258) is a pan receptor tyrosine kinase (RTK) inhibitor that targets VEGFR, FGFR, PDGFR, and KIT. It is being widely tested for treatment of various cancers." ], "exact_answer": [ [ "VEGFR" ], [ "FGFR" ], [ "PDGFR" ], [ "KIT" ] ], "type": "list", "id": "5a7486a90384be9551000003", "snippets": [ { "offsetInBeginSection": 291, "offsetInEndSection": 436, "text": "Dovitinib, a potent FGFR inhibitor, has demonstrated antitumor activity in heavily pretreated patients with FGFR pathway-amplified breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28183331", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 423, "text": "Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28213002", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 989, "text": "Dovitinib (TKI-258/CHIR-258) is a pan receptor tyrosine kinase (RTK) inhibitor that targets VEGFR, FGFR, PDGFR, and KIT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28342996", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 189, "text": "Dovitinib, a suppressor of FGFR activity, may be active in ACC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28377480", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 277, "text": "We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in patients progressing on anti-VEGF treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736761", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 672, "text": "Five HNSCC cell lines were characterized based on VEGFR1-3 and FGFR1-4 expression by sqRT-PCR and treated with three different tyrosine kinase inhibitors (TKIs) (nintedanib, dovitinib and pazopanib), all of which are effective against VEGFR and FGFR family members.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28714017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29101463", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1039, "text": ".RESULTS: Four trials involving the selective VEGFR inhibitors axitinib, tivozanib and dovitinib were analysed, all using sorafenib as the comparator. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26723100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "PURPOSE: Dovitinib (TKI258) is an oral multi-tyrosine kinase inhibitor of FGFR, VEGFR, PDGFR \u03b2, and c-Kit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27100354", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 797, "text": "Using this PDX model, we confirmed the ability of the FGFR inhibitors, ponatinib, dovitinib and BGJ398, to modulate FGFR signaling, inhibit cell proliferation and induce cell apoptosis in cholangiocarcinoma tumors harboring FGFR2 fusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27216979", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 429, "text": "In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27082062", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 1074, "text": "AZD4547, BGJ398 (infigratinib), Debio-1347 and dovitinib are FGFR1/2/3 inhibitors; BLU9931 is a selective FGFR4 inhibitor; FIIN-2, JNJ-42756493, LY2874455 and ponatinib are pan-FGFR inhibitors. AZD4547, dovitinib and ponatinib are multi-kinase inhibitors targeting FGFRs, colony stimulating factor\u00a01 receptor\u00a0(CSF1R), vascular endothelial growth factor\u00a0(VEGF)R2, and others. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27245147", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1291, "text": "In vitro, N87-TR cell lines demonstrated a higher sensitivity than did trastuzumab-sensitive parental cells to the FGFR3 inhibitor dovitinib, which reduced expression of pAKT, ZEB1, and cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27267856", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 286, "text": "The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27315356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27025387", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1127, "text": "We tested various T-ALL cell lines against a small-molecule inhibitor screen of 66 compounds targeting two-thirds of the tyrosine kinome and found that combined treatment of T-ALL cells with dovitinib, an orally active multi-targeted small-molecule receptor tyrosine kinase inhibitor, and OP449 synergistically reduced the viability of all tested T-ALL cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27705940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confer resistance to the pan-FGFR inhibitor, dovitinib, and explore the mechanism of action of the drug-resistant mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23908597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Dovitinib is a novel multi-target tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-1-3, platelet-derived growth factor receptor-\u03b2, Fms-like tyrosine kinase 3, c-Kit and fibroblast growth factor receptor-1-3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25683141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Dovitinib (TKI258/CHIR258) is a multi-kinase inhibitor in phase III development for the treatment of several cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23041231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "INTRODUCTION Erlotinib is a FDA approved small molecule inhibitor of epidermal growth factor receptor and dovitinib is a novel small molecule inhibitor of fibroblast growth factor and vascular endothelial growth factor receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149476", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 378, "text": "Here, we explore the therapeutic potential of 2 FGFR inhibitors, the multikinase inhibitor dovitinib (TKI258) and the more selective FGFR inhibitor NVP-BGJ398 for the treatment of endometrial cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23443805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "PURPOSE Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29101463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The multiple kinase inhibitor dovitinib is currently under clinical investigation for hepatocellular carcinoma (HCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22180308", "endSection": "abstract" } ] }, { "body": "How do circRNAs relate to tumorigenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "http://www.ncbi.nlm.nih.gov/pubmed/28622299" ], "ideal_answer": [ "Circular RNA may promote or repress tumorigenesis." ], "type": "summary", "id": "5a9922981d1251d03b000007", "snippets": [ { "offsetInBeginSection": 1371, "offsetInEndSection": 1890, "text": "Upregulation of FBXW7-185aa in cancer cells inhibited proliferation and cell cycle acceleration, while knockdown of FBXW7-185aa promoted malignant phenotypes invitro and invivo. FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc stabilization. Moreover, circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma clinical samples compared with their paired tumor-adjacent tissues (P<.001). Circ-FBXW7 expression positively associated with glioblastoma patient overall survival (P = .03).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 484, "text": "We report here the tumorigenic capacity of a circRNA derived from angiomotin-like1 (circ-Amotl1). Circ-Amotl1 is highly expressed in patient tumor samples and cancer cell lines. Single-cell inoculations using circ-Amotl1-transfected tumor cells showed a 30-fold increase in proliferative capacity relative to control. Agarose colony-formation assays similarly revealed a 142-fold increase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622299", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 880, "text": " Subcutaneous single-cell injections led to the formation of palpable tumors in 41% of mice, with tumor sizes>1\u2009cm3in 1 month. We further found that this potent tumorigenicity was triggered through interactions between circ-Amotl1 and c-myc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622299", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1355, "text": "Our study therefore reveals a novel function of circRNAs in tumorigenesis, and this subclass of noncoding RNAs may represent a potential target in cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622299", "endSection": "abstract" } ] }, { "body": "Which method is available for whole genome identification of pathogenic regulatory variants in mendelian disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27569544" ], "ideal_answer": [ "Genomiser" ], "exact_answer": [ "Genomiser" ], "type": "factoid", "id": "5a67c497b750ff4455000012", "snippets": [ { "offsetInBeginSection": 216, "offsetInEndSection": 717, "text": "Here we present Genomiser, an analysis framework that is able not only to score the relevance of variation in the non-coding genome, but also to associate regulatory variants to specific Mendelian diseases. Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to\u00a0discover variants associated to specific Mendelian disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 927, "text": "Overall, Genomiser is able to identify causal regulatory variants as the\u00a0top candidate in 77% of simulated whole genomes, allowing effective detection and discovery of regulatory variants in Mendelian disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 422, "text": "Here we present Genomiser, an analysis framework that is able not only to score the relevance of variation in the non-coding genome, but also to associate regulatory variants to specific Mendelian diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 929, "text": "Overall, Genomiser is able to identify causal regulatory variants as the\u00a0top candidate in 77% of simulated whole genomes, allowing effective detection and discovery of regulatory variants in Mendelian disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 718, "text": "Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to\u00a0discover variants associated to specific Mendelian disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 717, "text": "Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to\u00a0discover variants associated to specific Mendelian disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 928, "text": "Overall, Genomiser is able to identify causal regulatory variants as the\u00a0top candidate in 77% of simulated whole genomes, allowing effective detection and discovery of regulatory variants in Mendelian disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" } ] }, { "body": "Is pregabalin effective for sciatica?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26633090", "http://www.ncbi.nlm.nih.gov/pubmed/28328324" ], "ideal_answer": [ "No. Treatment with pregabalin did not significantly reduce the intensity of leg pain associated with sciatica and did not significantly improve other outcomes, as compared with placebo, over the course of 8 weeks. The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D012585", "http://www.biosemantics.org/jochem#4236113", "https://meshb.nlm.nih.gov/record/ui?ui=D000069583" ], "type": "yesno", "id": "5a70ec6899e2c3af2600000c", "snippets": [ { "offsetInBeginSection": 1871, "offsetInEndSection": 2202, "text": "CONCLUSIONS: Treatment with pregabalin did not significantly reduce the intensity of leg pain associated with sciatica and did not significantly improve other outcomes, as compared with placebo, over the course of 8 weeks. The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28328324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Whilst pregabalin (PGB) and gabapentin (GBP) are both used to treat neuropathic pain, their relative role in sciatica is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26633090", "endSection": "abstract" }, { "offsetInBeginSection": 571, "offsetInEndSection": 734, "text": "GBP and PGB appeared to demonstrate comparable efficacy and SE. However, the amount and quality of evidence was low, and only indirect comparisons were available. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26633090", "endSection": "abstract" } ] }, { "body": "Can gas vesicles be detected by ultrasound?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27351374" ], "ideal_answer": [ "Gas vesicles have been identified as nanoscale reporters for ultrasound." ], "exact_answer": "yes", "type": "yesno", "id": "5a9d30241d1251d03b00001b", "snippets": [ { "offsetInBeginSection": 187, "offsetInEndSection": 357, "text": "Gas vesicles-genetically encoded protein nanostructures isolated from buoyant photosynthetic microbes-have recently been identified as nanoscale reporters for ultrasound.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27351374", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1041, "text": "Here, we demonstrate that genetic engineering of gas vesicles results in nanostructures with new mechanical, acoustic, surface, and functional properties to enable harmonic, multiplexed, and multimodal ultrasound imaging as well as cell-specific molecular targeting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27351374", "endSection": "abstract" } ] }, { "body": "In what phase of clinical trials is crenezumab? (November 2017)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28720101" ], "ideal_answer": [ "Crenezumab is undergoing phase III clinical trials." ], "exact_answer": [ "Phase III" ], "type": "factoid", "id": "5a9acd921d1251d03b000016", "snippets": [ { "offsetInBeginSection": 1424, "offsetInEndSection": 1569, "text": "Ongoing Phase III clinical trials via passive immunotherapy against A\u03b2 peptides (crenezumab, gantenerumab, and aducanumab) seem to be promising. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28720101", "endSection": "abstract" } ] }, { "body": "Which sequence-based algorithm for branch point prediction has been proposed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28633445" ], "ideal_answer": [ "BPP is a sequence-based algorithm for branch point prediction." ], "exact_answer": [ "BPP" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000465" ], "type": "factoid", "id": "5a76160a83b0d9ea66000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "BPP: a sequence-based algorithm for branch point prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28633445", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "BPP: a sequence-based algorithm for branch point prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28633445", "endSection": "title" } ] }, { "body": "What organism causes scarlet fever also known as scarletina?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10405382", "http://www.ncbi.nlm.nih.gov/pubmed/19868695", "http://www.ncbi.nlm.nih.gov/pubmed/23305889", "http://www.ncbi.nlm.nih.gov/pubmed/19868926", "http://www.ncbi.nlm.nih.gov/pubmed/8219499", "http://www.ncbi.nlm.nih.gov/pubmed/15232184", "http://www.ncbi.nlm.nih.gov/pubmed/26850399", "http://www.ncbi.nlm.nih.gov/pubmed/2772682", "http://www.ncbi.nlm.nih.gov/pubmed/17532590", "http://www.ncbi.nlm.nih.gov/pubmed/24168973", "http://www.ncbi.nlm.nih.gov/pubmed/23735582", "http://www.ncbi.nlm.nih.gov/pubmed/23639381", "http://www.ncbi.nlm.nih.gov/pubmed/8440944", "http://www.ncbi.nlm.nih.gov/pubmed/19947304", "http://www.ncbi.nlm.nih.gov/pubmed/2045646", "http://www.ncbi.nlm.nih.gov/pubmed/10961536", "http://www.ncbi.nlm.nih.gov/pubmed/28322696", "http://www.ncbi.nlm.nih.gov/pubmed/1500078" ], "ideal_answer": [ "Scarlet fever is a disease which can occur as a result of a group A streptococcus (group A strep), group C Streptococcus and Streptococcus hemolyticus infection." ], "exact_answer": [ "Group A Streptococcus or Streptococcus pyogenes" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D012541", "http://www.disease-ontology.org/api/metadata/DOID:8596" ], "type": "factoid", "id": "5aa55b45d6d6b54f7900000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Scarlet fever is one of a variety of diseases caused by group A Streptococcus (GAS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23735582", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1427, "text": "In a small epidemic of scarlet fever a healthy carrier of hemolytic streptococcus was detected; the organism carried was identical in its serological reactions with strains of hemolytic streptococci isolated from active cases of scarlet fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19868695", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 371, "text": "No morphological or cultural characteristics peculiar to the hemolytic streptococcus from scarlet fever can be demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19868695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 0, "text": "Application of multilocus enzyme electrophoresis and comparative sequencing of the gene (speA) encoding streptococcal pyrogenic exotoxin a (scarlet fever toxin) revealed that new waves of scarlet fever are associated with an increase in frequency of S. pyogenes clones carrying variant speA alleles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8440944", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 748, "text": "Additionally, S. pyogenes induces toxin-mediated syndromes, i. e. scarlet fever, streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19947304", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 165, "text": "Group A Streptococcus (GAS) is the only pathogen known to cause scarlet fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23305889", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 466, "text": "We present a case that illustrates the distinctive clinical spectrum of A. hemolyticum infections that may be confused with drug allergy, group A streptococcal scarlet fever, diphtheria, and even toxic shock syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2045646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "1. Hemolytic streptococcus has been found in 100 per cent of the throats of patients with scarlet fever during the 1st week of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19868695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Group C beta-hemolytic streptococci causing pharyngitis and scarlet fever.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2772682", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Several outbreaks of scarlet fever caused by Streptococcus pyogenes were recently reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24168973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Little information is available on the differences in frequency of pyrogenic exotoxin genes between strains of group A streptococci that cause scarlet fever and those that cause pharyngotonsillitis in children in Taiwan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23639381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Molecular characterization of Group A streptococcal isolates causing scarlet fever and pharyngitis among young children: a retrospective study from a northern Taiwan medical center.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23639381", "endSection": "title" }, { "offsetInBeginSection": 26, "offsetInEndSection": 70, "text": "group A streptococcus causing scarlet fever ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17532590", "endSection": "title" }, { "offsetInBeginSection": 26, "offsetInEndSection": 70, "text": "scarlet-fever-related group A streptococcal,", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26850399", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Infection with group A beta-hemolytic streptococci (GABHS) is the most common bacterial cause of acute pharyngitis and tonsillitis beyond infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10961536", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1668, "text": "scarlet fever is a local infection of the throat by a particular type of Streptococcus haemolyticus capable of producing a toxin which is absorbed and is the cause of the general manifestations of the disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19868926", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 917, "text": "an epidemic by S.pyogenes type 1 with many cases of toxic shock was observed, the same type caused a scarlet fever epidemic without complications in eastern Germany.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1500078", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 221, "text": "clinical Streptococcus pyogenes strains causing scarlet fever and the streptococcal toxic shock-like syndrome (TSLS).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8219499", "endSection": "title" }, { "offsetInBeginSection": 25, "offsetInEndSection": 211, "text": "Streptococcus pyogenes (group A Streptococcus - GAS) is an important human pathogen which causes a variety of diseases, including tonsillopharyngitis, scarlet fever and rheumatic fever. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15232184", "endSection": "abstract" }, { "offsetInBeginSection": 23, "offsetInEndSection": 144, "text": "OF STREPTOCOCCUS : II. ANTIGENIC RELATIONSHIPS BETWEEN STRAINS OF STREPTOCOCCUS HAEMOLYTICUS ISOLATED FROM SCARLET FEVER.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19868695", "endSection": "title" } ] }, { "body": "What is the BioArchive system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28716596", "http://www.ncbi.nlm.nih.gov/pubmed/15812389", "http://www.ncbi.nlm.nih.gov/pubmed/18682250" ], "ideal_answer": [ "A small-scale automated cryopreservation and storage system (Mini-BioArchive system) used in the banking of umbilical cord blood (UCB) units." ], "exact_answer": [ "automated cryopreservation and storage system" ], "type": "factoid", "id": "5a9d8a651d1251d03b00001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Umbilical cord blood (CB) banks usually freeze and store CB for clinical transplantation using conventional controlled-rate freezer or the automated BioArchive system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28716596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The performance of a small-scale automated cryopreservation and storage system (Mini-BioArchive system) used in the banking of umbilical cord blood (UCB) units was evaluated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18682250", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 675, "text": "To validate the use of the sample attached to the UCB unit as a quality-control tool for the final product, UCB units (n = 20) stored in liquid nitrogen with the Bioarchive system were analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15812389", "endSection": "abstract" } ] }, { "body": "Which algorithm has been proposed for efficient storage of WGS variant calls?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28334390" ], "ideal_answer": [ "Whole-genome sequencing (WGS) data are being generated at an unprecedented rate. Analysis of WGS data requires a flexible data format to store the different types of DNA variation. Variant call format (VCF) is a general text-based format developed to store variant genotypes and their annotations. However, VCF files are large and data retrieval is relatively slow. 'SeqArray' is a new WGS variant data format implemented in the R/Bioconductor package for storing variant calls in an array-oriented manner which provides the same capabilities as VCF, but with multiple high compression options and data access using high-performance parallel computing." ], "exact_answer": [ "SeqArray" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000465" ], "type": "factoid", "id": "5a76179d83b0d9ea66000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "SeqArray-a storage-efficient high-performance data format for WGS variant calls.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334390", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1341, "text": "Whole-genome sequencing (WGS) data are being generated at an unprecedented rate. Analysis of WGS data requires a flexible data format to store the different types of DNA variation. Variant call format (VCF) is a general text-based format developed to store variant genotypes and their annotations. However, VCF files are large and data retrieval is relatively slow. Here we introduce a new WGS variant data format implemented in the R/Bioconductor package 'SeqArray' for storing variant calls in an array-oriented manner which provides the same capabilities as VCF, but with multiple high compression options and data access using high-performance parallel computing.Results: Benchmarks using 1000 Genomes Phase 3 data show file sizes are 14.0\u2009Gb (VCF), 12.3\u2009Gb (BCF, binary VCF), 3.5\u2009Gb (BGT) and 2.6\u2009Gb (SeqArray) respectively. Reading genotypes in the SeqArray package are two to three times faster compared with the htslib C library using BCF files. For the allele frequency calculation, the implementation in the SeqArray package is over 5 times faster than PLINK v1.9 with VCF and BCF files, and over 16 times faster than vcftools. When used in conjunction with R/Bioconductor packages, the SeqArray package provides users a flexible, feature-rich, high-performance programming environment for analysis of WGS variant data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334390", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 859, "text": "Here we introduce a new WGS variant data format implemented in the R/Bioconductor package 'SeqArray' for storing variant calls in an array-oriented manner which provides the same capabilities as VCF, but with multiple high compression options and data access using high-performance parallel computing.
Results: Benchmarks using 1000 Genomes Phase 3 data show file sizes are 14.0\u2009Gb (VCF), 12.3\u2009Gb (BCF, binary VCF), 3.5\u2009Gb (BGT) and 2.6\u2009Gb (SeqArray) respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334390", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1593, "text": "When used in conjunction with R/Bioconductor packages, the SeqArray package provides users a flexible, feature-rich, high-performance programming environment for analysis of WGS variant data.
Availability and Implementation: http://www.bioconductor.org/packages/SeqArray.
Contact: zhengx@u.washington.edu.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334390", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 678, "text": "Here we introduce a new WGS variant data format implemented in the R/Bioconductor package 'SeqArray' for storing variant calls in an array-oriented manner which provides the same capabilities as VCF, but with multiple high compression options and data access using high-performance parallel computing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334390", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1350, "text": "When used in conjunction with R/Bioconductor packages, the SeqArray package provides users a flexible, feature-rich, high-performance programming environment for analysis of WGS variant data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "SeqArray-a storage-efficient high-performance data format for WGS variant calls.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334390", "endSection": "title" } ] }, { "body": "Is Citrobacter rodentium pathogenic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28085133", "http://www.ncbi.nlm.nih.gov/pubmed/27624779", "http://www.ncbi.nlm.nih.gov/pubmed/27821583", "http://www.ncbi.nlm.nih.gov/pubmed/27633986" ], "ideal_answer": [ "Yes, the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases." ], "exact_answer": "yes", "type": "yesno", "id": "5aa4faaed6d6b54f7900000b", "snippets": [ { "offsetInBeginSection": 759, "offsetInEndSection": 855, "text": "One day after colonization, mice were infected with the colonic pathogen, Citrobacter rodentium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27633986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "The human pathogen enteropathogenic Escherichia coli (EPEC), as well as the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27624779", "endSection": "abstract" }, { "offsetInBeginSection": 1578, "offsetInEndSection": 1624, "text": "EPEC-like mouse pathogen Citrobacter rodentium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085133", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 581, "text": "Here, we develop a model that provides that link for the investigation of Citrobacter rodentium infection, a mouse model for enteropathogenic Escherichia coli (EPEC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27821583", "endSection": "abstract" } ] }, { "body": "List two human monoclonal antibodies against Clostridium difficile toxins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "http://www.ncbi.nlm.nih.gov/pubmed/28121498", "http://www.ncbi.nlm.nih.gov/pubmed/25451052", "http://www.ncbi.nlm.nih.gov/pubmed/28274145", "http://www.ncbi.nlm.nih.gov/pubmed/25486992", "http://www.ncbi.nlm.nih.gov/pubmed/28730660", "http://www.ncbi.nlm.nih.gov/pubmed/27757389" ], "ideal_answer": [ "Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. They were shown to decrease Clostridium difficile recurrence. Bezlotoxumab was approved by the Food and Drug Administration and the European Medicines Agency for Clostridium difficile recurrence." ], "exact_answer": [ [ "actoxumab" ], [ "bezlotoxumab" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000911" ], "type": "list", "id": "5a7240aa2dc08e987e00000d", "snippets": [ { "offsetInBeginSection": 157, "offsetInEndSection": 266, "text": "Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28121498", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 814, "text": "Notably, the authors lay emphasis on the phase III clinical trial (MODIFY II), which allowed bezlotoxumab to be approved by the Food and Drug Administration and the European Medicines Agency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28274145", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 811, "text": "Bezlotoxumab, a human monoclonal antibody that binds and neutralizes C. difficile toxin B, is the first therapeutic agent to receive United States Food and Drug Administration approval for the prevention of CDI recurrence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28730660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The Monoclonal Antitoxin Antibodies (Actoxumab-Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27757389", "endSection": "title" }, { "offsetInBeginSection": 400, "offsetInEndSection": 625, "text": "Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) toC. difficiletoxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27757389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B developed by Merck&Co. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Mechanisms of protection against Clostridium difficile infection by the monoclonal antitoxin antibodies actoxumab and bezlotoxumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25486992", "endSection": "title" }, { "offsetInBeginSection": 485, "offsetInEndSection": 710, "text": "A combination of human monoclonal antibodies, actoxumab and bezlotoxumab, directed against TcdA and TcdB, respectively, has been shown to decrease the rate of recurrence in patients treated with standard-of-care antibiotics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25486992", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 294, "text": " Actoxumab and bezlotoxumab are human monoclonal antibodies that neutralize the cytotoxic/cytopathic effects of TcdA and TcdB, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25451052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B developed by Merck & Co.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "endSection": "abstract" } ] }, { "body": "List ribosomal biogenesis proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28332494", "http://www.ncbi.nlm.nih.gov/pubmed/27994142", "http://www.ncbi.nlm.nih.gov/pubmed/28123053", "http://www.ncbi.nlm.nih.gov/pubmed/29143558", "http://www.ncbi.nlm.nih.gov/pubmed/28549781" ], "ideal_answer": [ "FGF13\np53\nTGF\u03b2/Activin\nPTEN\nNucleostemin\nHEATR1" ], "exact_answer": [ [ "FGF13" ], [ "p53" ], [ "TGF\u03b2/Activin" ], [ "PTEN" ], [ "Nucleostemin" ], [ "HEATR1" ] ], "type": "list", "id": "5aa80873d6d6b54f79000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Regulatory module involving FGF13, miR-504, and p53 regulates ribosomal biogenesis and supports cancer cell survival.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27994142", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "TGF\u03b2/Activin signalling is required for ribosome biogenesis and cell growth in Drosophila salivary glands.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28123053", "endSection": "title" }, { "offsetInBeginSection": 780, "offsetInEndSection": 906, "text": " our results show that TGF\u03b2/Activin signalling is required for ribosomal biogenesis, a key aspect of cellular growth control. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28123053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "PTEN\u03b2 is an alternatively translated isoform of PTEN that regulates rDNA transcription.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28332494", "endSection": "title" }, { "offsetInBeginSection": 194, "offsetInEndSection": 269, "text": "Nucleostemin (NS) is a nucleolar protein that controls ribosomal biogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28549781", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1176, "text": "These findings reveal an important role for HEATR1 in ribosome biogenesis and further support the concept that perturbation of ribosome biosynthesis results in p53-dependent cell cycle checkpoint activation, with implications for human pathologies including cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143558", "endSection": "abstract" } ] }, { "body": "Which protein is regulated by Tudor interacting repair regulator (TIRR)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14602918", "http://www.ncbi.nlm.nih.gov/pubmed/28213517", "http://www.ncbi.nlm.nih.gov/pubmed/28241136" ], "ideal_answer": [ "Tudor interacting repair regulator (TIRR) regulates P53-binding protein 1 (53BP1) by masking its histone methyl-lysine binding function." ], "exact_answer": [ "P53-binding protein 1", "53BP1" ], "concepts": [ "http://www.uniprot.org/uniprot/TIRR_CHICK", "https://meshb.nlm.nih.gov/record/ui?ui=D000071856", "http://www.uniprot.org/uniprot/TIRR_MOUSE", "https://meshb.nlm.nih.gov/record/ui?ui=D011506", "http://www.uniprot.org/uniprot/TIRR_HUMAN" ], "type": "factoid", "id": "5a774fdcfaa1ab7d2e000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "The p53-binding protein 1-Tudor-interacting repair regulator complex participates in the DNA damage response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28213517", "endSection": "title" }, { "offsetInBeginSection": 627, "offsetInEndSection": 1462, "text": "In this study, we identified the Tudor-interacting repair regulator (TIRR) that specifically associates with the ionizing radiation-induced foci formation region of 53BP1. 53BP1 and TIRR form a stable complex, which is required for their expression. Moreover, the 53BP1-TIRR complex dissociates after DNA damage, and this dissociation may be ataxia telangiectasia mutated-dependent. Similar to 53BP1, loss of TIRR restores PARPi resistance in BRCA1-deficient cells. Collectively, our data identified a novel 53BP1-TIRR complex in DNA damage response. TIRR may play both positive and negative roles in 53BP1 regulation. On the one hand, it stabilizes 53BP1 and thus positively regulates 53BP1. On the other hand, its association with 53BP1 prevents 53BP1 localization to sites of DNA damage, and thus TIRR is also an inhibitor of 53BP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28213517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "TIRR regulates 53BP1 by masking its histone methyl-lysine binding function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1200, "text": "P53-binding protein 1 (53BP1) is a multi-functional double-strand break repair protein that is essential for class switch recombination in B lymphocytes and for sensitizing BRCA1-deficient tumours to poly-ADP-ribose polymerase-1 (PARP) inhibitors. Central to all 53BP1 activities is its recruitment to double-strand breaks via the interaction of the tandem Tudor domain with dimethylated lysine 20 of histone H4 (H4K20me2). Here we identify an uncharacterized protein, Tudor interacting repair regulator (TIRR), that directly binds the tandem Tudor domain and masks its H4K20me2 binding motif. Upon DNA damage, the protein kinase ataxia-telangiectasia mutated (ATM) phosphorylates 53BP1 and recruits RAP1-interacting factor 1 (RIF1) to dissociate the 53BP1-TIRR complex. However, overexpression of TIRR impedes 53BP1 function by blocking its localization to double-strand breaks. Depletion of TIRR destabilizes 53BP1 in the nuclear-soluble fraction and alters the double-strand break-induced protein complex centring 53BP1. These findings identify TIRR as a new factor that influences double-strand break repair using a unique mechanism of masking the histone methyl-lysine binding function of 53BP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 798, "text": "In this study, we identified the Tudor-interacting repair regulator (TIRR) that specifically associates with the ionizing radiation-induced foci formation region of 53BP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28213517", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1204, "text": "These findings identify TIRR as a new factor that influences double-strand break repair using a unique mechanism of masking the histone methyl-lysine binding function of 53BP1.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 770, "text": "Upon DNA damage, the protein kinase ataxia-telangiectasia mutated (ATM) phosphorylates 53BP1 and recruits RAP1-interacting factor 1 (RIF1) to dissociate the 53BP1-TIRR complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 876, "text": "53BP1 and TIRR form a stable complex, which is required for their expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28213517", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1023, "text": "Depletion of TIRR destabilizes 53BP1 in the nuclear-soluble fraction and alters the double-strand break-induced protein complex centring 53BP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 879, "text": "However, overexpression of TIRR impedes 53BP1 function by blocking its localization to double-strand breaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The p53-binding protein 1-Tudor-interacting repair regulator complex participates in the DNA damage response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28213517", "endSection": "title" }, { "offsetInBeginSection": 168, "offsetInEndSection": 258, "text": "Moreover, p53 stimulates the topoisomerase I-induced recombination repair (TIRR) reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "TIRR regulates 53BP1 by masking its histone methyl-lysine binding function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "title" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1201, "text": "These findings identify TIRR as a new factor that influences double-strand break repair using a unique mechanism of masking the histone methyl-lysine binding function of 53BP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28241136", "endSection": "abstract" } ] }, { "body": "Which algorithm is used for detection of long repeat expansions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28887402" ], "ideal_answer": [ "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. For that purpose, ExpansionHunter has been developed as a software tool that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length." ], "exact_answer": [ "ExpansionHunter" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D019680", "https://meshb.nlm.nih.gov/record/ui?ui=D042622" ], "type": "factoid", "id": "5a804f71faa1ab7d2e00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1547, "text": "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of theC9orf72repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2786/2789, 95% CI [0.997, 1.00]) of the wild-type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples in which every sample had one of eight different pathogenic repeat expansions, including those associated with fragile X syndrome, Friedreich's ataxia, and Huntington's disease, and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887402", "endSection": "abstract" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1549, "text": "Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887402", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 508, "text": "We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887402", "endSection": "abstract" } ] }, { "body": "Which brain tumors does neuroligin-3 promote?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28959975" ], "ideal_answer": [ "Neuroligin-3 promotes the growth of high-grade gliomas." ], "exact_answer": [ "high-grade gliomas" ], "type": "factoid", "id": "5a9ac4e81d1251d03b000011", "snippets": [ { "offsetInBeginSection": 605, "offsetInEndSection": 1576, "text": "An important mechanism that mediates this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic adhesion molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K-mTOR pathway. However, the necessity of NLGN3 for glioma growth, the proteolytic mechanism of NLGN3 secretion, and the further molecular consequences of NLGN3 secretion in glioma cells remain unknown. Here we show that HGG growth depends on microenvironmental NLGN3, identify signalling cascades downstream of NLGN3 binding in glioma, and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of paediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. NLGN3 stimulates several oncogenic pathways, such as early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes that include upregulation of several synapse-related genes in glioma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28959975", "endSection": "abstract" }, { "offsetInBeginSection": 1794, "offsetInEndSection": 1913, "text": "This work defines a promising strategy for targeting NLGN3 secretion, which could prove transformative for HGG therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28959975", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 81, "text": "Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28959975", "endSection": "title" } ] }, { "body": "Which web resource for LIR motif-containing proteins in eukaryotes has been developed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27484196" ], "ideal_answer": [ "In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, the iLIR database ( https://ilir.warwick.ac.uk ) has been developed as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis." ], "exact_answer": [ "The iLIR database" ], "type": "factoid", "id": "5a8056a2faa1ab7d2e00001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "iLIR database: A web resource for LIR motif-containing proteins in eukaryotes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27484196", "endSection": "title" }, { "offsetInBeginSection": 625, "offsetInEndSection": 1848, "text": "In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10\u00a0years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database ( https://ilir.warwick.ac.uk ) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27484196", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1670, "text": "Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database ( https://ilir.warwick.ac.uk ) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27484196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "iLIR database: a web resource for LIR motif-containing proteins in eukaryotes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27484196", "endSection": "title" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1671, "text": "Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database ( https://ilir.warwick.ac.uk ) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27484196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "iLIR database: A web resource for LIR motif-containing proteins in eukaryotes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27484196", "endSection": "title" } ] }, { "body": "What is liquid liquid phase transition?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27725777", "http://www.ncbi.nlm.nih.gov/pubmed/28980860", "http://www.ncbi.nlm.nih.gov/pubmed/25436423" ], "ideal_answer": [ "The influence of membrane-free microcompartments resulting from crowding-induced liquid/liquid phase separation (LLPS) on the dynamic spatial organization of FtsZ, the main component of the bacterial division machinery, has been studied using several LLPS systems." ], "exact_answer": [ "membrane-free microcompartments" ], "type": "factoid", "id": "5aa6c800d6d6b54f79000012", "snippets": [ { "offsetInBeginSection": 980, "offsetInEndSection": 1190, "text": "engaged in or are at least related to the physiological liquid-liquid phase transitions (LLPTs) leading to the formation of various proteinaceous membrane-less organelles (PMLOs), both normal and pathological. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28980860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The influence of membrane-free microcompartments resulting from crowding-induced liquid/liquid phase separation (LLPS) on the dynamic spatial organization of FtsZ, the main component of the bacterial division machinery, has been studied using several LLPS systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27725777", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 193, "text": "we hypothesize that intrinsically disordered proteins (IDPs) serve as important drivers of the intracellular liquid-liquid phase separations that generate various membrane-less organelles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436423", "endSection": "abstract" } ] }, { "body": "Can CD55 deficiency cause thrombosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26205796", "http://www.ncbi.nlm.nih.gov/pubmed/23020629", "http://www.ncbi.nlm.nih.gov/pubmed/22696589", "http://www.ncbi.nlm.nih.gov/pubmed/22077430", "http://www.ncbi.nlm.nih.gov/pubmed/25237200", "http://www.ncbi.nlm.nih.gov/pubmed/28657829", "http://www.ncbi.nlm.nih.gov/pubmed/11843289", "http://www.ncbi.nlm.nih.gov/pubmed/23765390", "http://www.ncbi.nlm.nih.gov/pubmed/27812245", "http://www.ncbi.nlm.nih.gov/pubmed/28516949" ], "ideal_answer": [ "Yes, loss of CD55 is associated with thrombosis in patients with Paroxysmal nocturnal hemoglobinuria. CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55" ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0060903", "https://meshb.nlm.nih.gov/record/ui?ui=D013927" ], "type": "yesno", "id": "5a723cd12dc08e987e00000b", "snippets": [ { "offsetInBeginSection": 883, "offsetInEndSection": 1056, "text": " The loss of CD55 and CD59 renders PNH erythrocytes susceptible to intravascular haemolysis, which can lead to thrombosis and to much of the morbidity and mortality of PNH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657829", "endSection": "title" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1475, "text": "CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657829", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 854, "text": "It is caused by the expansion of a hematopoietic progenitor cell that has acquired a mutation in the X-linked phosphatidylinositol glycan class A (PIGA) gene that results in deficiency of the glycosylphosphatidylinositol anchor structure responsible for fixing a wide spectrum of proteins particularly CD55 and CD59. The clinical features of this disease arise as a result of complement-mediated hemolysis in unprotected red cells, leukocytes, and platelets as well as the release of free hemoglobin. Patients may present with a variety of clinical manifestations, such as anemia, thrombosis, kidney disease, smooth muscle dystonias, abdominal pain, dyspnea, and extreme fatigue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812245", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 445, "text": "The lack of one of the GPI-AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure and thrombosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26205796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25237200", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1164, "text": "RESULTS: CD55 and/or CD59 deficiencies were found in 1.6% (2/127) of patients with primary BCS, 1.0% (1/100) of non-malignant and non-cirrhotic patients with PVT, and 4.7% (4/85) of cirrhotic patients with PVT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23020629", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 983, "text": "Data of this study indicate that the PNH defect as detected with CD55, CD59, and CD16 is not an important cause of intra-abdominal thrombosis in northwestern India.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696589", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1146, "text": "PNH testing of red blood cells revealed a CD55 and CD59 deficiency consistent with PNH in both cases. The systemic complications typically associated with thrombosis were not observed for the following several months with early conservative treatments including eculizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23765390", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 426, "text": "Deficiency of the GPI-anchored complement inhibitors CD55 and CD59 on erythrocytes leads to intravascular hemolysis upon complement activation. Apart from hemolysis, another prominent feature is a highly increased risk of thrombosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22077430", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1514, "text": "Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation.
CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by a decrease or absence of glycosylphosphatidylinositol (GPI)-anchored molecules such as CD55 and CD59 from the surface of affected cells, resulting in intravascular hemolysis, cytopenia, and venous thrombosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11843289", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1479, "text": "CONCLUSIONS CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657829", "endSection": "abstract" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1434, "text": "CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657829", "endSection": "title" } ] }, { "body": "What is the approximate size of gas vesicles?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/807555" ], "ideal_answer": [ "The diameter of gas vesicles is approximately 100nm." ], "exact_answer": [ "100 nm" ], "type": "factoid", "id": "5a9d31711d1251d03b00001c", "snippets": [ { "offsetInBeginSection": 379, "offsetInEndSection": 514, "text": "This number remained relatively constant while the size of the vesicles increased until they attained their maximum diamtere of 100 nm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/807555", "endSection": "abstract" } ] }, { "body": "Are sleep apnea and snoring associated with cardiac arrhythmias?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28209226", "http://www.ncbi.nlm.nih.gov/pubmed/16293956", "http://www.ncbi.nlm.nih.gov/pubmed/28992834", "http://www.ncbi.nlm.nih.gov/pubmed/3542725", "http://www.ncbi.nlm.nih.gov/pubmed/20351955", "http://www.ncbi.nlm.nih.gov/pubmed/331948", "http://www.ncbi.nlm.nih.gov/pubmed/7774322", "http://www.ncbi.nlm.nih.gov/pubmed/28040290", "http://www.ncbi.nlm.nih.gov/pubmed/22160956", "http://www.ncbi.nlm.nih.gov/pubmed/10613491", "http://www.ncbi.nlm.nih.gov/pubmed/22520295", "http://www.ncbi.nlm.nih.gov/pubmed/25252161", "http://www.ncbi.nlm.nih.gov/pubmed/17655678", "http://www.ncbi.nlm.nih.gov/pubmed/27914359", "http://www.ncbi.nlm.nih.gov/pubmed/28181212", "http://www.ncbi.nlm.nih.gov/pubmed/22826063", "http://www.ncbi.nlm.nih.gov/pubmed/18024169", "http://www.ncbi.nlm.nih.gov/pubmed/8178007", "http://www.ncbi.nlm.nih.gov/pubmed/16149210", "http://www.ncbi.nlm.nih.gov/pubmed/3106890", "http://www.ncbi.nlm.nih.gov/pubmed/2654251" ], "ideal_answer": [ "Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050847", "https://meshb.nlm.nih.gov/record/ui?ui=D012891", "http://www.disease-ontology.org/api/metadata/DOID:9220", "https://meshb.nlm.nih.gov/record/ui?ui=D012913", "http://www.disease-ontology.org/api/metadata/DOID:0050848", "https://meshb.nlm.nih.gov/record/ui?ui=D020181", "https://meshb.nlm.nih.gov/record/ui?ui=D020182", "https://meshb.nlm.nih.gov/record/ui?ui=D001049" ], "type": "yesno", "id": "5a981dd0fcd1d6a10c00002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA), a common breathing disorder, is an independent risk factor for AF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28040290", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "There is a growing consensus in the scientific community that suggests a strong association between obstructive sleep apnea (OSA) and cardiovascular (CVD) conditions and events, including coronary artery disease, hypertension, arrhythmia, heart failure, and sudden cardiac death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914359", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 386, "text": "part from well-established risk factors that increase the odds for the development of AF, e.g. age or arterial hypertension, recent analyses indicate that obstructive sleep apnoea (OSA) may independently, negatively modify the arrhythmia occur-rence profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28181212", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 489, "text": "Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28209226", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 390, "text": "Severe snoring may be associated with pulmonary and systemic hypertension, secondary polycythemia, and cardiac arrhythmias.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3106890", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 386, "text": "Severe snoring may be associated with pulmonary and systemic hypertension, secondary polycythemia, and cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3106890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "BACKGROUND AND PURPOSE Nocturnal cardiac arrhythmias occur in patients with obstructive sleep apnea (OSA), reportedly as a consequence of the autonomic effects of recurrent apnea with subsequent oxygen desaturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18024169", "endSection": "abstract" }, { "offsetInBeginSection": 2295, "offsetInEndSection": 2500, "text": "Obstructive apnea is associated with myocardial ischemia (silent or symptomatic), acute coronary events, stroke and transient ischemic attacks, cardiac arrhythmia, pulmonary hypertension and heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16149210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 725, "text": "Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing, affecting 5-15% of the population. It is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture, and is typically associated with excessive daytime sleepiness, snoring, and witnessed apneas. Patients with obstructive sleep apnea present risk to the general public safety by causing 8-fold increase in vehicle accidents, and they may themselves also suffer from the physiologic consequences of OSA; these include hypertension, coronary artery disease, stroke, congestive heart failure, pulmonary hypertension, and cardiac arrhythmias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16293956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Obstructive sleep apnea and central sleep apnea with Cheyne-Stokes respiration are associated with an increased risk of cardiac arrhythmia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22160956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Obstructive sleep apnea (OSA) affects approximately 4% of middle-aged men and 2% of middle-aged women. Cardiac arrhythmias are common problems in patients with OSA, even though the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17655678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Cardiac arrhythmias during wakefulness and sleep in 15 patients with sleep-induced obstructive apnea, and the effect of atropine and tracheostomy on these arrhythmias were studied by continuous overnight Holter electrocardiographic, respiratory and electroencephalographic recordings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/331948", "endSection": "abstract" }, { "offsetInBeginSection": 49, "offsetInEndSection": 410, "text": "obstructive sleep apnea (OSA) as its most extreme variant, is characterized by intermittent episodes of partial or complete obstruction of the upper airway, leading to cessation of breathing while asleep. Cardiac arrhythmias are common problems in OSA patients, although the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20351955", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 183, "text": "The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25252161", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 281, "text": " Recent studies have shown that cardiac arrhythmias and conduction disorders are common in patients with SA. Sleep apnea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22520295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Severity of nocturnal cardiac arrhythmias correlates with intensity of sleep apnea in men", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22826063", "endSection": "title" }, { "offsetInBeginSection": 282, "offsetInEndSection": 380, "text": "Patients affected with OSA are frequently hypertensive and can have dangerous cardiac arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2654251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Patients with stable cardiac failure who snore may present sleep hypopnea and cardiac arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8178007", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 170, "text": " Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Cardiac arrhythmias are common in patients with OSA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28992834", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 386, "text": "Nocturnal hypoxia has been associated with serious ventricular tachyarrhythmias as well as life-threatening bradyarrhythmias. Obesity and snoring, both of which increase with age, have been identified as risk factors for sleep-related breathing disorders, as have hypertension and heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3542725", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 381, "text": "Obstructive sleep apnea syndrome is associated with excess daytime sleepiness, depression, and an increased incidence of ischemic cardiopathy, cardiac arrhythmias, systemic hypertension and brain infarction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10613491", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 654, "text": "We found 58 percent prevalence of arrhythmias in patients with sleep apnea (apnea/hypopnea index = AHI>10), vs 42 percent in nonapneic controls (chi 2 = 16.7, p<0.0001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7774322", "endSection": "abstract" } ] }, { "body": "Are osteoclasts specialized in bone degradation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27761364", "http://www.ncbi.nlm.nih.gov/pubmed/22090285", "http://www.ncbi.nlm.nih.gov/pubmed/24088021", "http://www.ncbi.nlm.nih.gov/pubmed/23742809", "http://www.ncbi.nlm.nih.gov/pubmed/26466547" ], "ideal_answer": [ "Bone degradation is caused by osteoclasts, the normal bone-resorbing cells." ], "exact_answer": "yes", "type": "yesno", "id": "5aa82180d6d6b54f79000015", "snippets": [ { "offsetInBeginSection": 1649, "offsetInEndSection": 1683, "text": "osteoclast-mediated attack on bone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26466547", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 215, "text": "Bone degradation is caused by osteoclasts, the normal bone-resorbing cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27761364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Cathepsin K is a highly potent collagenase in osteoclasts and is responsible for bone degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24088021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "In osteoclasts, Src controls podosome organization and bone degradation, which leads to an osteopetrotic phenotype in src(-/-) mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Bone degradation by osteoclasts depends on the formation of a sealing zone, composed of an interlinked network of podosomes, which delimits the degradation lacuna into which osteoclasts secrete acid and proteolytic enzymes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090285", "endSection": "abstract" } ] }, { "body": "List BET proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28068333", "http://www.ncbi.nlm.nih.gov/pubmed/28733670", "http://www.ncbi.nlm.nih.gov/pubmed/28063381", "http://www.ncbi.nlm.nih.gov/pubmed/25575605", "http://www.ncbi.nlm.nih.gov/pubmed/26590112" ], "ideal_answer": [ "BRD2\nBRD3\nBRD4\nBdf1" ], "exact_answer": [ [ "Brd2" ], [ "Brd4" ], [ "Bdf1" ], [ "Brd3" ] ], "type": "list", "id": "5aacdcf1fcf4565872000009", "snippets": [ { "offsetInBeginSection": 76, "offsetInEndSection": 233, "text": "Bromodomain-containing protein 2 (Brd2), which belongs to the bromodomain and extraterminal domain family of proteins, suppresses adipocyte differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25575605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "BRD4 is a member of the BET (bromodomain and extraterminal domain) family proteins ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26590112", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 275, "text": "the role of the BET protein Bdf1 has been explored in Saccharomyces cerevisiae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28068333", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 687, "text": "BET proteins BRD2, BRD3 and BRD4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28733670", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 439, "text": " inhibition of Brd4, a BET family member", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28063381", "endSection": "abstract" } ] }, { "body": "Does temsirolimus improve survival of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21493184", "http://www.ncbi.nlm.nih.gov/pubmed/24692729", "http://www.ncbi.nlm.nih.gov/pubmed/27143690", "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "http://www.ncbi.nlm.nih.gov/pubmed/16012795", "http://www.ncbi.nlm.nih.gov/pubmed/23099651", "http://www.ncbi.nlm.nih.gov/pubmed/22033322", "http://www.ncbi.nlm.nih.gov/pubmed/17538086" ], "ideal_answer": [ "No. Temsirolimus does not prolong survival of gliobalstoma patients." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D010361", "http://www.biosemantics.org/jochem#4239515", "https://meshb.nlm.nih.gov/record/ui?ui=D005909", "https://meshb.nlm.nih.gov/record/ui?ui=D013534" ], "type": "yesno", "id": "5a733a672dc08e987e000014", "snippets": [ { "offsetInBeginSection": 542, "offsetInEndSection": 1013, "text": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259301", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1710, "text": "CONCLUSIONS: Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27143690", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1378, "text": "The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27143690", "endSection": "abstract" }, { "offsetInBeginSection": 1227, "offsetInEndSection": 1450, "text": "CONCLUSION: The combination of bevacizumab with temsirolimus was well-tolerated and resulted in stable disease of at least four months/partial response in three out of six pediatric patients with chemorefractory CNS tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24692729", "endSection": "abstract" }, { "offsetInBeginSection": 1363, "offsetInEndSection": 1654, "text": "CONCLUSIONS: Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22033322", "endSection": "abstract" }, { "offsetInBeginSection": 1244, "offsetInEndSection": 1476, "text": "Novel targeted agents such as bevacizumab, imatinib, erlotinib, temsirolimus, immunotherapy, cilengitide, talampanel, etc. are helping classical chemotherapeutic agents, like temozolomide, to achieve an increase in overall survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21493184", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1431, "text": "CONCLUSIONS: CCI-779 was well tolerated at this dose schedule; however, there was no evidence of efficacy in patients with recurrent GBM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16012795", "endSection": "abstract" }, { "offsetInBeginSection": 1823, "offsetInEndSection": 1891, "text": "The addition of temsirolimus to interferon did not improve survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17538086", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1716, "text": "CONCLUSIONS Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27143690", "endSection": "abstract" }, { "offsetInBeginSection": 1778, "offsetInEndSection": 1846, "text": "The addition of temsirolimus to interferon did not improve survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17538086", "endSection": "abstract" } ] }, { "body": "What is the proteoform?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27989944", "http://www.ncbi.nlm.nih.gov/pubmed/28453668", "http://www.ncbi.nlm.nih.gov/pubmed/28414281", "http://www.ncbi.nlm.nih.gov/pubmed/26670565" ], "ideal_answer": [ "Although proteomics has rapidly developed in the past decade, researchers are still in the early stage of exploring the world of complex proteoforms, which are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes" ], "exact_answer": [ "proteoforms are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes" ], "type": "factoid", "id": "5aad4b37fcf456587200000a", "snippets": [ { "offsetInBeginSection": 679, "offsetInEndSection": 812, "text": "proteoforms - splice variants, single amino acid substitutions (SAP variants), and post-translational modifications (PTM) of proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28414281", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 349, "text": "Although proteomics has rapidly developed in the past decade, researchers are still in the early stage of exploring the world of complex proteoforms, which are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453668", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1384, "text": "Protein species (aka proteoforms) function at their molecular level, and diverse structures and biological roles of every proteoform come from often co-occurring proteolysis, amino acid variation and post-translational modifications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27989944", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 763, "text": "the identification of novel proteoforms is also made possible based on detection of novel translation initiation sites (cognate or near-cognate), novel transcript isoforms, sequence variation or novel (small) open reading frames in intergenic or un-translated genic regions by analyzing high-throughput sequencing data from RNAseq or ribosome profiling experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26670565", "endSection": "abstract" } ] }, { "body": "Are there sex differences in the transcriptome of the mouse hippocampus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28302071" ], "ideal_answer": [ "There are sex differences in the transcriptome of the developing mouse hippocampus." ], "exact_answer": "yes", "type": "yesno", "id": "5a991ee21d1251d03b000005", "snippets": [ { "offsetInBeginSection": 205, "offsetInEndSection": 499, "text": "To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we used a developmental series of female and male mice at 1, 2, and 4 months of age to assess both mRNA and protein in the hippocampus with RNA-sequencing and mass-spectrometry, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28302071", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 1144, "text": "The bulk of these differentially expressed genes are changed in both sexes at one or more ages, but a total of 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation through postnatal development, 8 of which are heat-shock proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28302071", "endSection": "abstract" }, { "offsetInBeginSection": 1394, "offsetInEndSection": 1643, "text": "Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28302071", "endSection": "abstract" } ] }, { "body": "How does neuronal activity affect neuroligin-3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25957677" ], "ideal_answer": [ "Neuronal activity-induces secretion of neuroligin-3." ], "exact_answer": [ "Induces secretion" ], "type": "factoid", "id": "5a9ac6821d1251d03b000012", "snippets": [ { "offsetInBeginSection": 113, "offsetInEndSection": 317, "text": "In this issue of Cell, Venkatesh et al. demonstrate that this also occurs in the brain, identifying neuronal activity-induced secretion of neuroligin-3 as a novel mechanism promoting glioma proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25957677", "endSection": "abstract" } ] }, { "body": "What is the role of the blood-brain barrier?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27425887", "http://www.ncbi.nlm.nih.gov/pubmed/27633771", "http://www.ncbi.nlm.nih.gov/pubmed/19664711", "http://www.ncbi.nlm.nih.gov/pubmed/26995317" ], "ideal_answer": [ "The blood\u2013brain barrier (BBB) is a highly selective semipermeable membrane barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS). The blood\u2013brain barrier is formed by brain endothelial cells and it allows the passage of water, some gases, and lipid-soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001812" ], "type": "summary", "id": "5aa0495bd6d6b54f79000002", "snippets": [ { "offsetInBeginSection": 343, "offsetInEndSection": 544, "text": "the blood-brain barrier (BBB), a highly specialized endothelial cell membrane that lines cerebral microvessels, represents the interface between neural cells and circulating cells of the immune system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27425887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The blood-brain barrier (BBB) plays a key role in maintaining the specialized microenvironment of the central nervous system (CNS), and enabling communication with the systemic compartment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26995317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "The blood-brain barrier (BBB) is composed of brain capillary endothelial cells and has an important role in maintaining homeostasis of the brain separating the blood from the parenchyma of the central nervous system (CNS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27633771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The physical barrier between blood and the CNS (the blood-brain barrier, the blood-spinal cord barrier and the blood-CSF barrier) protects the CNS from both toxic and pathogenic agents in the blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19664711", "endSection": "abstract" } ] }, { "body": "Sclerostin regulates what process?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20043874", "http://www.ncbi.nlm.nih.gov/pubmed/27342581", "http://www.ncbi.nlm.nih.gov/pubmed/25248363", "http://www.ncbi.nlm.nih.gov/pubmed/23737439", "http://www.ncbi.nlm.nih.gov/pubmed/22836717", "http://www.ncbi.nlm.nih.gov/pubmed/28571484", "http://www.ncbi.nlm.nih.gov/pubmed/24949665", "http://www.ncbi.nlm.nih.gov/pubmed/26826396", "http://www.ncbi.nlm.nih.gov/pubmed/24151757", "http://www.ncbi.nlm.nih.gov/pubmed/22206666", "http://www.ncbi.nlm.nih.gov/pubmed/27742498", "http://www.ncbi.nlm.nih.gov/pubmed/27965160", "http://www.ncbi.nlm.nih.gov/pubmed/12702725", "http://www.ncbi.nlm.nih.gov/pubmed/23233270", "http://www.ncbi.nlm.nih.gov/pubmed/23845326", "http://www.ncbi.nlm.nih.gov/pubmed/21991382", "http://www.ncbi.nlm.nih.gov/pubmed/28081119", "http://www.ncbi.nlm.nih.gov/pubmed/22082361", "http://www.ncbi.nlm.nih.gov/pubmed/21890009", "http://www.ncbi.nlm.nih.gov/pubmed/21312267" ], "ideal_answer": [ "Sclerostin plays a critical role in bone homeostasis and its deficiency or pharmacological neutralization increases bone formation" ], "exact_answer": [ "bone metabolism" ], "concepts": [ "http://www.uniprot.org/uniprot/SOST_MOUSE", "http://www.uniprot.org/uniprot/SOST_BOVIN", "http://www.uniprot.org/uniprot/SOST_CHLAE" ], "type": "factoid", "id": "5a9700adfcd1d6a10c00002c", "snippets": [ { "offsetInBeginSection": 82, "offsetInEndSection": 326, "text": " Sclerostin is a soluble antagonist of Wnt/\u03b2-catenin signaling secreted primarily by osteocytes. Current evidence indicates that sclerostin likely functions as a local/paracrine regulator of bone metabolism rather than as an endocrine hormone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27965160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27742498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21312267", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The osteocyte product sclerostin is emerging as an important paracrine regulator of bone mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23737439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Sclerostin is a secreted inhibitor of Wnt signaling and plays an essential role in the regulation of bone mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21890009", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 172, "text": "Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28081119", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 207, "text": "Sclerostin negatively regulates Wnt signaling pathway and also has an important role in postmenopausal bone loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26826396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Sclerostin regulates bone formation by inhibiting Wnt pathway signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22836717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Sclerostin, an osteocyte-expressed negative regulator of bone formation, is one of the inhibitors of Wnt signaling that is a critical pathway in the correct process of osteoblast differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22082361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Sclerostin, a secreted glycoprotein, regulates osteoblast function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20043874", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 202, "text": "Sclerostin regulates bone formation by inhibiting Wnt/\u03b2-catenin signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845326", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1167, "text": "We suggest that sclerostin negatively regulates the formation of bone by repressing the differentiation and/or function of osteoblasts induced by BMPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12702725", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 214, "text": "Sclerostin negatively regulates Wnt signaling pathway and also has an important role in postmenopausal bone loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26826396", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1333, "text": "Since sclerostin expression is confined to the bone-resorbing osteoclast, it provides a mechanism whereby bone apposition is inhibited in the vicinity of resorption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12702725", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 201, "text": "Sclerostin regulates bone formation by inhibiting Wnt/\u03b2-catenin signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23845326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Sclerostin regulates release of bone mineral by osteocytes by induction of carbonic anhydrase 2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23737439", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "The secreted glycoprotein, sclerostin alters bone formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22206666", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 182, "text": "Sclerostin, encoded by the sost gene, and a product of the osteocyte, is a negative regulator of bone formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24949665", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 164, "text": "Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover, and it plays a role in cardiovascular calcification processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25248363", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 128, "text": " Sclerostin plays a major role in regulating skeletal bone mass, but its effects in articular cartilage are not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23233270", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 89, "text": "Sclerostin is a key negative regulator of bone formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24151757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Sclerostin is a product of mature osteocytes embedded in mineralised bone and is a negative regulator of bone mass and osteoblast differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21991382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "In humans, the SOST gene encodes sclerostin, an inhibitor of bone growth and remodeling, which also negatively regulates the bone repair process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28571484", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 93, "text": "The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27342581", "endSection": "abstract" } ] }, { "body": "What is PARP inhibitor (PARPi) resistance?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28255272", "http://www.ncbi.nlm.nih.gov/pubmed/28510338", "http://www.ncbi.nlm.nih.gov/pubmed/28069876" ], "ideal_answer": [ "PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs." ], "type": "summary", "id": "5aacd83ffcf4565872000008", "snippets": [ { "offsetInBeginSection": 361, "offsetInEndSection": 683, "text": "PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28255272", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1111, "text": "Recent studies have shown that PARP-1 could be either oncogenic or tumor suppressive in different cancers. PARP inhibitor resistance is also a growing concern in the clinical setting. Recently, changes in the levels of PARP-1 activity or expression in cancer patients have provided the basis for consideration of PARP-1 regulatory proteins as potential biomarkers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28510338", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 357, "text": "However, emerging data have also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28069876", "endSection": "abstract" } ] }, { "body": "What is the association of the protein RAB10 and Alzheimers disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26082458" ], "ideal_answer": [ "The genes SEC22B, RAB10 and FLT1 may be potential biomarkers of AD." ], "exact_answer": [ "RAB10 may be potential biomarkers of AD" ], "type": "factoid", "id": "5a9d8d691d1251d03b000020", "snippets": [ { "offsetInBeginSection": 1050, "offsetInEndSection": 1125, "text": "The target genes SEC22B, RAB10, and FLT1 may be potential biomarkers of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26082458", "endSection": "abstract" } ] }, { "body": "Does MC1R palmitoylation reduce pigmentation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28869973" ], "ideal_answer": [ "No, MC1R palmitoylation leads to increased pigmentation." ], "exact_answer": "no", "type": "yesno", "id": "5a9ac4161d1251d03b000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "The melanocortin-1 receptor (MC1R), a G-protein-coupled receptor, has a crucial role in human and mouse pigmentation. Activation of MC1R in melanocytes by \u03b1-melanocyte-stimulating hormone (\u03b1-MSH) stimulates cAMP signalling and melanin production and enhances DNA repair after ultraviolet irradiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28869973", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1203, "text": "MC1R palmitoylation, primarily mediated by the protein-acyl transferase ZDHHC13, is essential for activating MC1R signalling, which triggers increased pigmentation, ultraviolet-B-induced G1-like cell cycle arrest and control of senescence and melanomagenesis in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28869973", "endSection": "abstract" }, { "offsetInBeginSection": 1445, "offsetInEndSection": 1554, "text": "The results highlight a central role for MC1R palmitoylation in pigmentation and protection against melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28869973", "endSection": "abstract" } ] }, { "body": "A bite from the Lone Star Tick Amblyomma americanum, can cause the victim to become allergic to red meat, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28319627", "http://www.ncbi.nlm.nih.gov/pubmed/24690977" ], "ideal_answer": [ "Conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick, Ambyomma ameriacanum.", ".Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D017282" ], "type": "yesno", "id": "5a96c886fcd1d6a10c00002a", "snippets": [ { "offsetInBeginSection": 113, "offsetInEndSection": 512, "text": "A recent discovery of an IgE antibody specific to galactose-\u03b1-1,3-galactose, which is a carbohydrate abundantly expressed on cells and tissues of beef, pork, and lamb, adds one more tool to aid the clinician in making the appropriate diagnosis. A link has been discovered between the bite of the Lone Star Tick (Amblyomma americanum) and the development of sensitivity to galactose-\u03b1-1,3-galactose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24690977", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 535, "text": ". Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28319627", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 541, "text": "Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28319627", "endSection": "abstract" } ] }, { "body": "What are pQTLs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22595970", "http://www.ncbi.nlm.nih.gov/pubmed/18464913", "http://www.ncbi.nlm.nih.gov/pubmed/24586654", "http://www.ncbi.nlm.nih.gov/pubmed/25480033", "http://www.ncbi.nlm.nih.gov/pubmed/23172855", "http://www.ncbi.nlm.nih.gov/pubmed/24699359", "http://www.ncbi.nlm.nih.gov/pubmed/25657249" ], "ideal_answer": [ "The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways." ], "type": "summary", "id": "5a9d8ffe1d1251d03b000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "A genome-wide association study identifies protein quantitative trait loci (pQTLs).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18464913", "endSection": "title" }, { "offsetInBeginSection": 2013, "offsetInEndSection": 2165, "text": "The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18464913", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 502, "text": " Yet the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25657249", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 493, "text": "By studying the genetic variation affecting gene expression levels (cis expression quantitative trait loci [cis-eQTLs]) and protein levels (cis protein QTLs [cis-pQTLs]), we determined that young, primate-specific genes are enriched in cis-eQTLs and cis-pQTLs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25480033", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 787, "text": " Quantitative trait locus (QTL) analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs) with genome-wide significance on chromosomes 4, 5, 7, 12, and 17.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586654", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 959, "text": "We observed enrichment of protein quantitative trait loci (pQTLs) for cellular sensitivity to two commonly used chemotherapeutics: cisplatin and paclitaxel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24699359", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 618, "text": " Here, we assayed the abundance levels of proteins in plasma from 96 elderly Europeans using a new aptamer-based proteomic technology and performed genome-wide local (cis-) regulatory association analysis to identify protein quantitative trait loci (pQTL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22595970", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 651, "text": "we describe a proteomic quantitative trait locus (pQTL) study of plasma proteome screens in an F(2) intercross of 455 mice mapped with 177 genetic markers across the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23172855", "endSection": "abstract" } ] }, { "body": "What is Dysphoric Milk Ejection Reflex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20443435", "http://www.ncbi.nlm.nih.gov/pubmed/21645333", "http://www.ncbi.nlm.nih.gov/pubmed/29115857" ], "ideal_answer": [ "Dysphoric milk ejection reflex (D-MER) is characterized by an abrupt dysphoria, or undesirable feeling that occurs with the MER and continues for no more than a few minutes. After milk ejection, the dysphoria vanishes. Symptoms may decrease by 3 months or they may continue throughout the breastfeeding period." ], "type": "summary", "id": "5a70dfd599e2c3af26000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "BACKGROUND: Dysphoric milk ejection reflex (D-MER) is characterized by an abrupt dysphoria, or undesirable feeling that occurs with the MER and continues for no more than a few minutes. After milk ejection, the dysphoria vanishes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115857", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 482, "text": "All three women described the sudden onset of negative feelings at the initiation of each breastfeeding session. The dysphoria vanished after each milk ejection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Dysphoric Milk Ejection Reflex (D-MER) is an abrupt emotional \"drop\" that occurs in some women just before milk release and continues for not more than a few minutes. The brief negative feelings range in severity from wistfulness to self-loathing, and appear to have a physiological cause. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21645333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Dysphoric milk ejection reflex (D-MER) results in waves of negative emotions that last from shortly before initial milk ejection until baby starts to feed vigorously Symptoms may decrease by 3 months or they may continue throughout the breastfeeding period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20443435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "BACKGROUND: Dysphoric milk ejection reflex (D-MER) is characterized by an abrupt dysphoria, or undesirable feeling that occurs with the MER and continues for no more than a few minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": " Dysphoric Milk Ejection Reflex (D-MER) is an abrupt emotional \"drop\" that occurs in some women just before milk release and continues for not more than a few minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21645333", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 338, "text": "After milk ejection, the dysphoria vanishes.
CASE SERIES: This case series provides a report of three women who have experienced D-MER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115857", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 629, "text": "The dysphoria vanished after each milk ejection.
DISCUSSION: Literature on D-MER is limited to one published qualitative research study and two published case reports.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Dysphoric milk ejection reflex (D-MER) results in waves of negative emotions that last from shortly before initial milk ejection until baby starts to feed vigorously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20443435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Dysphoric Milk Ejection Reflex (D-MER) is an abrupt emotional \"drop\" that occurs in some women just before milk release and continues for not more than a few minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21645333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "BACKGROUND Dysphoric milk ejection reflex (D-MER) is characterized by an abrupt dysphoria, or undesirable feeling that occurs with the MER and continues for no more than a few minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Dysphoric milk ejection reflex (D-MER) is characterized by an abrupt dysphoria, or undesirable feeling that occurs with the MER and continues for no more than a few minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115857", "endSection": "abstract" } ] }, { "body": "Is Rucaparib effective for ovarian cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28751443", "http://www.ncbi.nlm.nih.gov/pubmed/28057616", "http://www.ncbi.nlm.nih.gov/pubmed/28205191", "http://www.ncbi.nlm.nih.gov/pubmed/27940438", "http://www.ncbi.nlm.nih.gov/pubmed/27087632", "http://www.ncbi.nlm.nih.gov/pubmed/28994564", "http://www.ncbi.nlm.nih.gov/pubmed/28916367", "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "http://www.ncbi.nlm.nih.gov/pubmed/28247266", "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "http://www.ncbi.nlm.nih.gov/pubmed/28264872", "http://www.ncbi.nlm.nih.gov/pubmed/28790837", "http://www.ncbi.nlm.nih.gov/pubmed/27908594" ], "ideal_answer": [ "Yes. Rucaparib is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has been approved for the treatment of patients with advanced ovarian cancer who have been treated with two or more chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:2394" ], "type": "yesno", "id": "5a7379a83b9d13c70800000a", "snippets": [ { "offsetInBeginSection": 3352, "offsetInEndSection": 3583, "text": "INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27908594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Rucaparib Approved for Ovarian Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28057616", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28057616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Rucaparib (Rubraca\u2122) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by Clovis Oncology, Inc. (Boulder, CO, USA) for the treatment of solid tumours. It has been approved in the USA as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28247266", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 971, "text": "In 2016, the US Food and Drug Administration approved three novel drugs for the treatment of solid malignancies-olaratumab in selected patients with soft-tissue sarcoma, atezolizumab for the treatment of bladder cancer, and rucaparib for the treatment of ovarian cancer; also in 2016, the use of previously approved anticancer agents (including atezolizumab) was expanded into 11 new patient populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28205191", "endSection": "abstract" }, { "offsetInBeginSection": 1591, "offsetInEndSection": 1709, "text": "Conclusions:Rucaparib was tolerable and had activity in patients with platinum-sensitive germlineBRCA1/2-mutated HGOC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28264872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "OBJECTIVE: To review the pharmacology, safety, efficacy, and the role of rucaparib in the treatment of relapsed, advanced ovarian cancer.
SUMMARY: A total of 2 phase I/II trials and 1 phase II trial have evaluated the safety and efficacy of oral rucaparib in ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 940, "text": "Rucaparib was found to be relatively well tolerated in clinical trials, with the most common adverse events being anemia, fatigue, and nausea.
CONCLUSION: Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 465, "text": "In patients with deleterious BRCA1/2 mutation, an overall response rate of 80% was achieved in the phase II trial Assessment of Rucaparib in Ovarian CancEr Trial 2 (ARIEL2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 756, "text": "This article summarizes the milestones in the development of rucaparib leading to this first approval for ovarian cancer.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28247266", "endSection": "abstract" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1775, "text": "These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Rucaparib: a Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "endSection": "title" }, { "offsetInBeginSection": 778, "offsetInEndSection": 914, "text": "CONCLUSION Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "endSection": "abstract" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1773, "text": "These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23729402", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 707, "text": "Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27087632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "BACKGROUND Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28916367", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 881, "text": "Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Rucaparib: A Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166829", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28790837", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation-Associated Advanced Ovarian Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28751443", "endSection": "title" }, { "offsetInBeginSection": 756, "offsetInEndSection": 865, "text": "Olaparib and rucaparib have been approved by the US FDA as monotherapy for advanced recurrent ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28994564", "endSection": "abstract" } ] }, { "body": "What is the \"protein inference problem\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22954624", "http://www.ncbi.nlm.nih.gov/pubmed/26935399", "http://www.ncbi.nlm.nih.gov/pubmed/17990506", "http://www.ncbi.nlm.nih.gov/pubmed/23385215", "http://www.ncbi.nlm.nih.gov/pubmed/28821210" ], "ideal_answer": [ "A major challenge in shotgun proteomics has been the assignment of identified peptides to the proteins from which they originate, referred to as the protein inference problem." ], "type": "summary", "id": "5aad547efcf456587200000b", "snippets": [ { "offsetInBeginSection": 763, "offsetInEndSection": 929, "text": " the protein inference problem still hampers the automatic assignment of peptide sequences to proteins, consequently impeding the quantification of sequence variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28821210", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 628, "text": "the protein inference problem can be regarded as a special protein quantification problem in the sense that truly present proteins are those proteins whose abundance values are not zero.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26935399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Protein inference is an important issue in proteomics research. Its main objective is to select a proper subset of candidate proteins that best explain the observed peptides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23385215", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 171, "text": "Assembling peptides identified from tandem mass spectra into a list of proteins, referred to as protein inference, is an important issue in shotgun proteomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22954624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "A major challenge in shotgun proteomics has been the assignment of identified peptides to the proteins from which they originate, referred to as the protein inference problem. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17990506", "endSection": "abstract" } ] }, { "body": "What is the link between lithium use during pregnancy and Ebstein anomaly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2743779", "http://www.ncbi.nlm.nih.gov/pubmed/27572669", "http://www.ncbi.nlm.nih.gov/pubmed/12114921", "http://www.ncbi.nlm.nih.gov/pubmed/23269033", "http://www.ncbi.nlm.nih.gov/pubmed/6518066", "http://www.ncbi.nlm.nih.gov/pubmed/16611133", "http://www.ncbi.nlm.nih.gov/pubmed/28591541", "http://www.ncbi.nlm.nih.gov/pubmed/15702702", "http://www.ncbi.nlm.nih.gov/pubmed/7666681", "http://www.ncbi.nlm.nih.gov/pubmed/3303067", "http://www.ncbi.nlm.nih.gov/pubmed/1346886", "http://www.ncbi.nlm.nih.gov/pubmed/2062397", "http://www.ncbi.nlm.nih.gov/pubmed/18982835", "http://www.ncbi.nlm.nih.gov/pubmed/2199873", "http://www.ncbi.nlm.nih.gov/pubmed/8031346" ], "ideal_answer": [ "It is generally believed that lithium use is associated with increased risk of Ebstein anomaly. However, more recent studies challenge this association." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004437", "http://www.disease-ontology.org/api/metadata/DOID:14289", "https://meshb.nlm.nih.gov/record/ui?ui=D008094" ], "type": "summary", "id": "5a7341fe2dc08e987e000018", "snippets": [ { "offsetInBeginSection": 373, "offsetInEndSection": 539, "text": "There is a possibility that, in particular, lithium may be associated with the Ebstein anomaly but present evidence cannot definitely affirm or deny this association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16611133", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1321, "text": "A profound ultrasound screening of the organs should be performed in case of lithium exposition, whereas newer studies showed no increase in risk for Ebstein anomaly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15702702", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 611, "text": "DATA EXTRACTION AND SYNTHESIS: In the 1970s a very strong association was suggested between maternal lithium treatment during pregnancy and Ebstein's anomaly of the heart in the offspring. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8031346", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1188, "text": "No women who took lithium during pregnancy were found among four case-control studies of Ebstein's anomaly involving 25, 34, 59, and 89 affected children, respectively. In two cohort studies, risk ratios of 3.0 (95% confidence interval [CI], 1.2 to 7.7) and 1.5 (95% CI, 0.4 to 6.8) for all congenital anomalies have been observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8031346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "[Ebstein's anomaly of the tricuspid valve following prenatal exposure to lithium].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2062397", "endSection": "title" }, { "offsetInBeginSection": 141, "offsetInEndSection": 388, "text": "An Ebstein's anomaly was diagnosed, with tricuspid valve insufficiency. Exposure to lithium in utero was established. Literature reports indicate an association between exposure to lithium in utero and cardiac anomalies, notably Ebstein's anomaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2062397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Lithium is widely used in the treatment of bipolar affective disorders, and teratogenic effects include cardiovascular abnormalities, notably Ebstein anomaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2199873", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 298, "text": " Some studies suggest that lithium might be involved as a teratogen increasing the incidence of Ebstein's anomaly in the offspring of female patients with manio-depressive psychosis and lithium-administered during pregnancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2743779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6518066", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 737, "text": "It is thought that this malformation is due to a direct teratogenic effect of lithium on the atrioventricular junction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7666681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "When lithium hurts: a look at Ebstein anomaly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23269033", "endSection": "title" }, { "offsetInBeginSection": 74, "offsetInEndSection": 297, "text": "Some studies suggest that lithium might be involved as a teratogen increasing the incidence of Ebstein's anomaly in the offspring of female patients with manio-depressive psychosis and lithium-administered during pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2743779", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 639, "text": "The search terms were lithium, pregnancy, teratogen, abnormalities (drug induced), Ebstein's anomaly, and adverse effects.
DATA EXTRACTION AND SYNTHESIS: In the 1970s a very strong association was suggested between maternal lithium treatment during pregnancy and Ebstein's anomaly of the heart in the offspring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8031346", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 275, "text": "In-utero exposure to lithium during the first trimester of pregnancy might be associated with an increased risk of cardiac malformations, especially the rare Ebstein's anomaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1346886", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 613, "text": "DATA EXTRACTION AND SYNTHESIS In the 1970s a very strong association was suggested between maternal lithium treatment during pregnancy and Ebstein's anomaly of the heart in the offspring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8031346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "BACKGROUND There has been concern that exposure to lithium early in pregnancy may be associated with a marked increase in the risk of Ebstein's anomaly (a right ventricular outflow tract obstruction defect) in infants and overall congenital cardiac defects, but data are conflicting and limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28591541", "endSection": "abstract" }, { "offsetInBeginSection": 1719, "offsetInEndSection": 1952, "text": "CONCLUSIONS Maternal use of lithium during the first trimester was associated with an increased risk of cardiac malformations, including Ebstein's anomaly; the magnitude of this effect was smaller than had been previously postulated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28591541", "endSection": "abstract" }, { "offsetInBeginSection": 1780, "offsetInEndSection": 2002, "text": "Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27572669", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1320, "text": "A profound ultrasound screening of the organs should be performed in case of lithium exposition, whereas newer studies showed no increase in risk for Ebstein anomaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15702702", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 344, "text": "Lithium exposure during the first trimester seems to increase the risk of congenital heart disease, especially Ebstein's anomaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3303067", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 675, "text": "Reported neonatal problems with maternal lithium therapy include Ebstein's anomaly, poor respiratory effort and cyanosis, rhythm disturbances, nephrogenic diabetes insipidus, thyroid dysfunction, hypoglycemia, hypotonia and lethargy, hyperbilirubinemia, and large-for-gestational-age infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12114921", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1074, "text": "All case control studies regarding Ebstein's anomaly were negative, and among 222 infants with Ebstein's anomaly and 44 with tricuspid atresia none of the mothers had taken lithium during pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18982835", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1026, "text": "1 patient in the lithium group chose to terminate pregnancy after Ebstein's anomaly was detected by a prenatal echocardiogram.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1346886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "When lithium hurts: a look at Ebstein anomaly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23269033", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 389, "text": "Literature reports indicate an association between exposure to lithium in utero and cardiac anomalies, notably Ebstein's anomaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2062397", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 536, "text": "In the 1970s a very strong association was suggested between maternal lithium treatment during pregnancy and Ebstein's anomaly of the heart in the offspring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8031346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6518066", "endSection": "title" }, { "offsetInBeginSection": 783, "offsetInEndSection": 951, "text": "No women who took lithium during pregnancy were found among four case-control studies of Ebstein's anomaly involving 25, 34, 59, and 89 affected children, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8031346", "endSection": "abstract" } ] }, { "body": "Does verubecestat activate BACE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28800329" ], "ideal_answer": [ "No, verubecestat is a potent BACE inhibitor." ], "exact_answer": "no", "type": "yesno", "id": "5a9d28981d1251d03b000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Verubecestat is a potent BACE1 enzyme inhibitor currently being investigated in Phase III trials for the treatment of mild-to-moderate and prodromal Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28800329", "endSection": "abstract" } ] }, { "body": "What does the Ribosome-bound Quality Control complex do?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28528489" ], "ideal_answer": [ "Ribosome-bound Quality Control complex (RQC), which recognizes nascent peptides translated from aberrant mRNAs, polyubiquitylates these aberrant peptides, extracts them from the stalled 60S subunit and finally escorts them to the proteasome for degradation." ], "type": "summary", "id": "5aa393b3d6d6b54f79000006", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 103, "text": "he ribosome-bound quality control complex: from aberrant peptide clearance to proteostasis maintenance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28528489", "endSection": "title" }, { "offsetInBeginSection": 226, "offsetInEndSection": 820, "text": "Among these processes, translational protein quality control is performed by the Ribosome-bound Quality Control complex (RQC), which recognizes nascent peptides translated from aberrant mRNAs, polyubiquitylates these aberrant peptides, extracts them from the stalled 60S subunit and finally escorts them to the proteasome for degradation. In this review, we focus on the mechanism of action of the RQC complex from stalled 60S binding to aberrant peptide delivery to the proteasome and describe the cellular consequences of a deficiency in the RQC pathway, such as aberrant protein aggregation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28528489", "endSection": "abstract" } ] }, { "body": "What is emicizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27405674", "http://www.ncbi.nlm.nih.gov/pubmed/27795538", "http://www.ncbi.nlm.nih.gov/pubmed/27885373", "http://www.ncbi.nlm.nih.gov/pubmed/28691557", "http://www.ncbi.nlm.nih.gov/pubmed/29042366" ], "ideal_answer": [ "ACE910 (emicizumab) is a humanized bispecific antibody recognizing factor IXa and X mimicking factor VIII function." ], "exact_answer": [ "ACE910 (emicizumab) is a humanized bispecific antibody recognizing factor IXa and X mimicking factor VIII function." ], "type": "factoid", "id": "5a9da8df4e03427e73000006", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 172, "text": "Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28691557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Emicizumab Prophylaxis in Hemophilia A with Inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28691557", "endSection": "title" }, { "offsetInBeginSection": 2055, "offsetInEndSection": 2218, "text": "Emicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no prophylaxis among participants with hemophilia A with inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28691557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Treatment and prevention of bleeding episodes in patients with severe haemophilia A require frequent intravenous injection of factor VIII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27885373", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 466, "text": "ACE910 (emicizumab) is a humanized bispecific antibody recognizing factor IXa and X mimicking factor VIII function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27795538", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 507, "text": "Emicizumab is a bispecific antibody recognizing both the enzyme factor IXa (FIXa) and the substrate factor X (FX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29042366", "endSection": "abstract" } ] }, { "body": "What illness is transmitted by the Lone Star Tick, Amblyomma americanum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19054615", "http://www.ncbi.nlm.nih.gov/pubmed/26336226", "http://www.ncbi.nlm.nih.gov/pubmed/19874183", "http://www.ncbi.nlm.nih.gov/pubmed/27729288", "http://www.ncbi.nlm.nih.gov/pubmed/21940418", "http://www.ncbi.nlm.nih.gov/pubmed/28319627", "http://www.ncbi.nlm.nih.gov/pubmed/25618142", "http://www.ncbi.nlm.nih.gov/pubmed/25118421", "http://www.ncbi.nlm.nih.gov/pubmed/17699076", "http://www.ncbi.nlm.nih.gov/pubmed/18452807", "http://www.ncbi.nlm.nih.gov/pubmed/19819631" ], "ideal_answer": [ "Amblyomma americanum (Lone star tick) is an important disease vector in the United States. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness [STARI] or Masters disease", "Today,A americanumremains an important vector for tick-borne illness. In addition to others, species ofRickettsia,Ehrlichia, andBorreliaare all transmitted by the lone star tick. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness." ], "exact_answer": [ [ "human monocytic ehrlichiosis" ], [ "tuleremia" ], [ "southern tick-associated rash illness [STARI] or Masters disease" ], [ "tide water spotted fever" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D017282" ], "type": "list", "id": "5a96c74cfcd1d6a10c000029", "snippets": [ { "offsetInBeginSection": 188, "offsetInEndSection": 367, "text": "Today,A americanumremains an important vector for tick-borne illness. In addition to others, species ofRickettsia,Ehrlichia, andBorreliaare all transmitted by the lone star tick. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28319627", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 535, "text": "Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28319627", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 387, "text": "Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21940418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Amblyomma americanum (Lone star tick) is an important disease vector in the United States. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25618142", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 529, "text": "E. chaffeensis is maintained in a complex cycle involving white-tailed deer (WTD; Odocoileus virginianus) as a primary reservoir and the lone star tick (LST; Amblyomma americanum) as a primary vector.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19819631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Amblyomma americanum, the lone star tick, is the most common and most aggressive human biting tick in the Southeastern United States. It is known to transmit the agents of human ehrlichioses, Ehrlichia chaffeensis and Ehrlichia ewingii. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25118421", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 481, "text": "Rickettsia parkeri is a member of the spotted fever group rickettsiae and causes a febrile illness in humans commonly referred to as \"Tidewater spotted fever\" or \"R. parkeri rickettsiosis.\" Although the Gulf Coast tick, Amblyomma maculatum Koch, is the primary vector of R. parkeri, a small proportion of A. americanum have also been shown to harbor R. parkeri. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26336226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18452807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Transmission of Ehrlichia chaffeensis from lone star ticks (Amblyomma americanum) to white-tailed deer (Odocoileus virginianus).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17699076", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Monocytic ehrlichiosis in people caused by the intracellular bacterium, Ehrlichia chaffeensis, is an emerging infectious disease transmitted by the lone star tick, Amblyomma americanum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "Southern tick-associated rash illness is a Lyme-like syndrome that occurs in the southern states. Borrelia lonestari, which has been suggested as a possible causative agent of southern tick-associated rash illness, naturally infects white-tailed deer (WTD; Odocoileus virginianus) and is transmitted by the lone star tick (Amblyomma americanum)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19874183", "endSection": "abstract" } ] }, { "body": "Which is the function of ubiquilins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19398896", "http://www.ncbi.nlm.nih.gov/pubmed/23046644", "http://www.ncbi.nlm.nih.gov/pubmed/27345149", "http://www.ncbi.nlm.nih.gov/pubmed/22628307", "http://www.ncbi.nlm.nih.gov/pubmed/24674348", "http://www.ncbi.nlm.nih.gov/pubmed/28933694", "http://www.ncbi.nlm.nih.gov/pubmed/28315615" ], "ideal_answer": [ "Ubiquilins, a family of ubiquitin-binding proteins, are involved in all protein degradation pathways. Ubiquilin (UBQLN) proteins are adaptors thought to link ubiquitinated proteins to the proteasome." ], "exact_answer": [ "Ubiquilins, a family of ubiquitin-binding proteins, are involved in all protein degradation pathways." ], "type": "factoid", "id": "5aa50086d6d6b54f7900000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Ubiquilin (UBQLN) proteins are adaptors thought to link ubiquitinated proteins to the proteasome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28315615", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 250, "text": "Ubiquilins are proteins that function as ubiquitin receptors in eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the genesis of neurodegenerative diseases. However, ubiquilin functions are still poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24674348", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 697, "text": "Ubiquitination and subsequently ubiquitin (Ub) receptor proteins (e.g., p62 and ubiquilins) are important common factors for targeting misfolded proteins to multiple quality control destinies, including the proteasome, lysosomes, and perhaps aggresomes, as well as for triggering mitophagy to remove defective mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23046644", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 538, "text": "We show that Ubiquilin family proteins bind transmembrane domains in the cytosol to prevent aggregation and temporarily allow opportunities for membrane targeting. Over time, Ubiquilins recruit an E3 ligase to ubiquitinate bound clients. The attached ubiquitin engages Ubiquilin's UBA domain, normally bound to an intramolecular UBL domain, and stabilizes the\u00a0Ubiquilin-client complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27345149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Ubiquilins (Ubqlns) are a family of ubiquitin receptors that promote the delivery of hydrophobic and aggregated ubiquitinated proteins to the proteasome for degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28933694", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 335, "text": " Ubiquilins, a family of ubiquitin-binding proteins, are involved in all protein degradation pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22628307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Ubiquilins (UBQLN), a family of adaptor proteins with partial homology with ubiquitin, are proposed to facilitate proteasomal degradation of ubiquitinated substrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398896", "endSection": "abstract" } ] }, { "body": "Which algorithm has been developed for prediction of protein subcellular localization using deep learning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29036616" ], "ideal_answer": [ "DeepLoc is an algorithm which has been developed for prediction of protein subcellular localization using deep learning." ], "exact_answer": [ "DeepLoc" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000465" ], "type": "factoid", "id": "5a7639419e632bc066000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "DeepLoc: prediction of protein subcellular localization using deep learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29036616", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "DeepLoc: prediction of protein subcellular localization using deep learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29036616", "endSection": "title" } ] }, { "body": "List the continent of origin for the brown marmorated stinkbug(Halyomorpha halys)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25474148", "http://www.ncbi.nlm.nih.gov/pubmed/29117381", "http://www.ncbi.nlm.nih.gov/pubmed/24787576", "http://www.ncbi.nlm.nih.gov/pubmed/22828257", "http://www.ncbi.nlm.nih.gov/pubmed/28824354", "http://www.ncbi.nlm.nih.gov/pubmed/29068708", "http://www.ncbi.nlm.nih.gov/pubmed/28824355", "http://www.ncbi.nlm.nih.gov/pubmed/26744454", "http://www.ncbi.nlm.nih.gov/pubmed/18069789", "http://www.ncbi.nlm.nih.gov/pubmed/29069361", "http://www.ncbi.nlm.nih.gov/pubmed/27581756", "http://www.ncbi.nlm.nih.gov/pubmed/26463187", "http://www.ncbi.nlm.nih.gov/pubmed/28430975", "http://www.ncbi.nlm.nih.gov/pubmed/28852110" ], "ideal_answer": [ "The brown marmorated stinkbug (Halyomorpha halys) is native to Asia" ], "exact_answer": [ [ "Asia" ] ], "type": "list", "id": "5a9eb008d6d6b54f79000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The brown marmorated stink bug, Halyomorpha halys (St\u00e5l) (BMSB) is an exotic invasive insect originating in East Asia, currently causing significant damage to fruits, vegetables and other crops throughout most of the Mid-Atlantic states of the U.S.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The brown marmorated stink bug, Halyomorpha halys (St\u00e5l), is a polyphagous pest indigenous to northeastern Asia where it damages various trees, vegetables, and leguminous crops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18069789", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 432, "text": "The brown marmorated stink bug (BMSB, Halyomorpha halys) is an East Asian species now established across North America and Europe, that in the Eastern United States of America (US) and Italy is causing significant economic losses to agriculture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The brown marmorated stink bug, Halyomorpha halys (St\u00e5l), is an invasive species native to regions of China, Japan, Korea, and Taiwan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28824355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The brown marmorated stink bug, Halyomorpha halys, a native of Asia, has become a serious invasive pest in the USA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24787576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The brown marmorated stink bug, Halyomorpha halys (St\u00e5l), native to China, Japan, and Korea, has emerged as a harmful invasive pest of a variety of crops in North America and Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28824354", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 737, "text": "The brown marmorated stink bug, Halyomorpha halys, is a highly polyphagous Asian herbivore and an economically important invasive pest in North America and Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27581756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Brown marmorated stink bug, Halyomorpha halys (St\u00e5l), (Hemiptera: Pentatomidae) is an invasive polyphagous agricultural and urban nuisance pest of Asian origin that is becoming widespread in North America and Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25474148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The brown marmorated stink bug, Halyomorpha halys, is native to Asia (China, Taiwan, Japan, and the Korean peninsula).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22828257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The brown marmorated stink bug, Halyomorpha halys (St\u00e5l), is an invasive species from Asia capable of causing severe agricultural damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "The brown marmorated stink bug, Halyomorpha halys (St\u00e5l) (BMSB) is an exotic invasive insect originating in East Asia, currently causing significant damage to fruits, vegetables and other crops throughout most of the Mid-Atlantic states of the U.S.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The brown marmorated stink bug (BMSB), Halyomorpha halys (St\u00e5l), is an invasive pentatomid introduced from Asia into the United States, Canada, multiple European countries, and Chile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29068708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "The invasive brown marmorated stink bug, Halyomorpha halys (St\u00e5l; Hemiptera: Pentatomidae), has recently emerged as a harmful pest of horticultural crops in North America and Europe. Native to East Asia, this highly polyphagous insect is spreading rapidly worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069361", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 267, "text": " The brown marmorated stink bug (BMSB), Halyomorpha halys (St\u00e5l) (Hemiptera: Pentatomidae), an invasive and polyphagous insect pest from Asia,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29117381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "The brown marmorated stink bug, Halyomorpha halys (St\u00e5l), is native to eastern Asia and is presently invading North America.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26744454", "endSection": "abstract" } ] }, { "body": "Please list 6 symptoms of Scarlet fever.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26585817", "http://www.ncbi.nlm.nih.gov/pubmed/29081840", "http://www.ncbi.nlm.nih.gov/pubmed/3619689", "http://www.ncbi.nlm.nih.gov/pubmed/26280141", "http://www.ncbi.nlm.nih.gov/pubmed/9339023", "http://www.ncbi.nlm.nih.gov/pubmed/1789905", "http://www.ncbi.nlm.nih.gov/pubmed/1919136" ], "ideal_answer": [ "Symptoms of scarlet fever include fever, rash, strawberry tongue and sore throat. In some cases other symptoms, angular stomatitis, tonsular exudate, and swollen lymph nodes are seen." ], "exact_answer": [ [ "fever" ], [ "rash" ], [ "sore throat" ], [ "strawberry tongue" ], [ "angular stomatitis" ], [ "swollen lymph nodes" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D012541", "http://www.disease-ontology.org/api/metadata/DOID:8596" ], "type": "list", "id": "5aa55b65d6d6b54f7900000e", "snippets": [ { "offsetInBeginSection": 318, "offsetInEndSection": 415, "text": "A fever is likely to occur with roseola, erythema infectiosum (fifth disease), and scarlet fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280141", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 908, "text": "The rash associated with scarlet fever usually develops on the upper trunk, then spreads throughout the body, sparing the palms and soles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Scarlet fever consists in a diffuse exanthem associated with mucous changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9339023", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 808, "text": "Cases of above-38 degrees C temperature were seen in about 81.4%, and from 2 to 5 days-duration of temperature were seen in 86.6% of the patients in the year 1976. Cases of above-moderate rash were observed in 68.2%, sever redness of throat in 29.9%, strawberry tongue in 86.3% and angular stomatitis in 37.7% of the patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1919136", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1484, "text": "ulture supernatants of strains without a detectable amount of the known ETs were highly mitogenic, indicating the production of other streptococcal mitogens. A correlation with clinical symptoms was determined with regard to exanthema and fever. Strains producing two or three toxins caused a more intense exanthema. Patient temperature was higher (greater than or equal to 38 degrees C) when the infecting strain produced ETB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1789905", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 669, "text": ") SI with a pronounced generalization including a pharyngeal one (31 cases), 4 of them with a rash (scarlet fever); extrapharyngeal (7 cases), 6 of them with a rash (scarlet fever); 2) SI without pronounced generalization (localized) including 33 cases with the involvement of the lungs and tonsilla and having an ordinary course and 11 cases of a sudden death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3619689", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 1081, "text": "A total of 171 out of 252 scarlet fever diagnoses were microbiologically verified in 158 patients. The median age was 3.8 years (interquartile range: 2.91-4.78), with the majority (57%) under the age of 4 years. There was fever in 89% of the processes (95% CI: 84-94%), with a temperature of>38\u00b0C in 73% (95% CI: 65-80%), enlarged lymph nodes in 70% (95% CI: 58-82%), absence of cough in 73% (95% CI: 65-80%), and tonsillar exudate in only 24% (95% CI: 17-31%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26585817", "endSection": "abstract" } ] }, { "body": "Gallbladder carriage is a well recognised means of spread of which bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25253258", "http://www.ncbi.nlm.nih.gov/pubmed/23732169", "http://www.ncbi.nlm.nih.gov/pubmed/24349565", "http://www.ncbi.nlm.nih.gov/pubmed/27600501", "http://www.ncbi.nlm.nih.gov/pubmed/25065707", "http://www.ncbi.nlm.nih.gov/pubmed/27131005" ], "ideal_answer": [ "Gallbladder carriage is associated with spread of Salmonella Typhi." ], "exact_answer": [ "Salmonella Typhi" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001419", "https://meshb.nlm.nih.gov/record/ui?ui=D005704" ], "type": "factoid", "id": "5a7347a02dc08e987e00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Carriage prevalence of Salmonella enterica serotype Typhi in gallbladders of adult autopsy cases from Mozambique.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27131005", "endSection": "title" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1008, "text": "CONCLUSIONS: We report a high prevalence of S. Typhi in gallbladders among adult autopsy cases from Mozambique.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27131005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Salmonella Extracellular Matrix Components Influence Biofilm Formation and Gallbladder Colonization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600501", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Salmonella enterica serovar Typhi, the causative agent of typhoid fever in humans, forms biofilms encapsulated by an extracellular matrix (ECM). Biofilms facilitate colonization and persistent infection in gallbladders of humans and mouse models of chronic carriage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600501", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "In vitro modeling of gallbladder-associated Salmonella spp. colonization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25253258", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "The host-pathogen interactions occurring in the gallbladder during Salmonella Typhi colonization contribute to typhoid fever pathogenesis during the acute and chronic stages of disease. The gallbladder is the primary reservoir during chronic typhoid carriage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25253258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder persistence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25065707", "endSection": "title" }, { "offsetInBeginSection": 216, "offsetInEndSection": 381, "text": "Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24349565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Gallbladder epithelium as a niche for chronic Salmonella carriage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23732169", "endSection": "title" }, { "offsetInBeginSection": 181, "offsetInEndSection": 483, "text": "This chronic state is highly associated with the presence of gallstones in the gallbladder of infected carriers upon which Salmonella can form robust biofilms. However, we hypothesize that in addition to gallstones, the gallbladder epithelium aids in the establishment/maintenance of chronic carriage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23732169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Carriage prevalence of Salmonella enterica serotype Typhi in gallbladders of adult autopsy cases from Mozambique.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27131005", "endSection": "title" } ] }, { "body": "What is included in the Mentzer index?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18445163", "http://www.ncbi.nlm.nih.gov/pubmed/26187724", "http://www.ncbi.nlm.nih.gov/pubmed/18192142", "http://www.ncbi.nlm.nih.gov/pubmed/8162086" ], "ideal_answer": [ "Mentzer index (MCV/RBC) is mean corpuscular volume (MCV) and red blood cell count (RBC) ratio. It is used for differentiation of thalassemia and iron deficiency anemia." ], "exact_answer": [ [ "mean corpuscular volume" ], [ "red blood cell count" ] ], "type": "list", "id": "5a736f0c3b9d13c708000007", "snippets": [ { "offsetInBeginSection": 608, "offsetInEndSection": 1010, "text": "In this study, macrocytic anemia due to FAD was defined as having an MCV \u2265100 fL and folic acid \u22646 ng/mL; pernicious anemia as having MCV \u2265100 fL, vitamin B12<200 pg/mL, and serum gastric parietal cell antibody positivity; iron deficiency anemia as having MCV<80 fL and iron<60 \u03bcg/dL; and thalassemia trait as having MCV<74 fL, red blood cell (RBC) count>5.0 \u00d7 10(12)/L, and Mentzer index (MCV/RBC)<13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26187724", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 876, "text": "Complete blood count (CBC) parameters of 2196 certainly diagnosed (1272 beta-thalassaemia minor and 924 iron deficiency) samples were used to evaluate the following indices and formulas: Bessman index (RDW), Mentzer formula (MCV/RBC), England and Fraser formula (MCV - RBC - 5 x Hb- 3.4), Shine and Lal formula (MCV2 x MCH/100), Ehsani formula (MCV-10 x RBC), Srivastava formula (MCH/RBC), Green and King formula (MCV2 x RDW/Hb x 100), red distribution width index RDWI (RDW x MCV/RBC), RDW/RBC, as well as our formula (MCV-RBC -3 x Hb). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18445163", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 525, "text": "The ratio of the mean corpuscular volume (MCV) and red blood cell count (RBC) can be automatically calculated with any of the newer hematology analyzers.METHODS: The results of 398 patient screens were collected. Data from the set were divided into training and validation subsets. The Mentzer ratio was determined through a receiver operating characteristic (ROC) curve on the first subset, and screened for thalassemia using the second subset. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18192142", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 889, "text": "Mentzer ratio MCV/RBC detected all cases of beta thalassemia but was a poor index for iron deficiency detection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8162086", "endSection": "abstract" } ] }, { "body": "Which disease is treated with Fexinidazole?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29113731", "http://www.ncbi.nlm.nih.gov/pubmed/22301556", "http://www.ncbi.nlm.nih.gov/pubmed/28552771", "http://www.ncbi.nlm.nih.gov/pubmed/27748443", "http://www.ncbi.nlm.nih.gov/pubmed/25409760", "http://www.ncbi.nlm.nih.gov/pubmed/24535888", "http://www.ncbi.nlm.nih.gov/pubmed/21200426", "http://www.ncbi.nlm.nih.gov/pubmed/21911566", "http://www.ncbi.nlm.nih.gov/pubmed/25694261", "http://www.ncbi.nlm.nih.gov/pubmed/24841257", "http://www.ncbi.nlm.nih.gov/pubmed/27611920", "http://www.ncbi.nlm.nih.gov/pubmed/22539226", "http://www.ncbi.nlm.nih.gov/pubmed/23133682" ], "ideal_answer": [ "Oral fexinidazole is effective for late-stage human african trypanosomiasis." ], "exact_answer": [ "human african trypanosomiasis" ], "concepts": [ "http://www.biosemantics.org/jochem#4257906" ], "type": "factoid", "id": "5a7373f63b9d13c708000008", "snippets": [ { "offsetInBeginSection": 150, "offsetInEndSection": 358, "text": "n the search for new therapeutics, the repurposing of the broad-spectrum antiprotozoal drug fexinidazole has completed Phase III trials with the anticipation that it will be the first oral treatment for HAT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28552771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113731", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 695, "text": "Therefore, we aimed to assess the safety and efficacy of an oral regimen of fexinidazole (a 2-substituted 5-nitroimidazole with proven trypanocidal activity) versus nifurtimox eflornithine combination therapy in patients with late-stage g-HAT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113731", "endSection": "abstract" }, { "offsetInBeginSection": 3197, "offsetInEndSection": 3406, "text": "INTERPRETATION: Our findings show that oral fexinidazole is effective and safe for the treatment of T b gambiense infection compared with nifurtimox eflornithine combination therapy in late-stage HAT patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "AIM: Fexinidazole (FEX) is a nitroimidazole being developed as a new trypanocide treatment for human African trypanosomiasis/sleeping sickness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27611920", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1244, "text": "We also observed that fexinidazole and fexinidazole sulfone are more effective than benznidazole and nifurtimox as curative treatments, particularly for acute stage infections, most likely as a result of the higher and more prolonged exposure of the sulfone derivative.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27748443", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 669, "text": "Specifically, the authors review the nitroimidazole compound fexinidazole, which is one of the few drugs which have reached Phase II trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409760", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 872, "text": "New tools considered include tiny targets for tsetse fly control, use of rapid diagnostic tests and oral treatment with fexinidazole or oxaboroles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25694261", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1729, "text": "Fexinidazole metabolites were effective in treating T. cruzi in a mouse model of acute infection, with cure rates superior to those achieved with either fexinidazole itself or benznidazole.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24841257", "endSection": "abstract" }, { "offsetInBeginSection": 1620, "offsetInEndSection": 2031, "text": "Fexinidazole treatment was also shown to reduce myocarditis in all animals infected with VL-10 or Colombian resistant T. cruzi strains, although parasite eradication was not achieved in all treated animals at the tested doses.
CONCLUSIONS: Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazole-susceptible, partially resistant, and resistant T. cruzi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133682", "endSection": "abstract" }, { "offsetInBeginSection": 1365, "offsetInEndSection": 1819, "text": "Fexinidazole is moderately active in vitro against African trypanosomes (IC\u2085\u2080 against laboratory strains and recent clinical isolates ranged between 0.16 and 0.93 \u00b5g/mL) and oral administration of fexinidazole at doses of 100 mg/kg/day for 4 days or 200 mg/kg/day for 5 days cured mice with acute and chronic infection respectively, the latter being a model for the advanced and fatal stage of the disease when parasites have disseminated into the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21200426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Fexinidazole: a potential new drug candidate for Chagas disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133682", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "BACKGROUND: New safe and effective treatments for Chagas disease (CD) are urgently needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Antitrypanosomal activity of fexinidazole metabolites, potential new drug candidates for Chagas disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24841257", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24535888", "endSection": "title" }, { "offsetInBeginSection": 192, "offsetInEndSection": 359, "text": "Here, we report that fexinidazole, a drug currently in phase 1 clinical trials for treating African trypanosomiasis, shows promise for treating visceral leishmaniasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22301556", "endSection": "abstract" }, { "offsetInBeginSection": 1832, "offsetInEndSection": 2005, "text": "CONCLUSIONS Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazole-susceptible, partially resistant, and resistant T. cruzi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133682", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 649, "text": "Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered following extensive compound mining by the Drugs for Neglected Diseases initiative and currently in Phase I clinical study for the treatment of human African trypanosomiasis, was evaluated in experimental models of acute and chronic CD caused by different strains of Trypanosoma cruzi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133682", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 694, "text": "Therefore, we aimed to assess the safety and efficacy of an oral regimen of fexinidazole (a 2-substituted 5-nitroimidazole with proven trypanocidal activity) versus nifurtimox eflornithine combination therapy in patients with late-stage g-HAT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113731", "endSection": "abstract" }, { "offsetInBeginSection": 3213, "offsetInEndSection": 3421, "text": "INTERPRETATION Our findings show that oral fexinidazole is effective and safe for the treatment of T b gambiense infection compared with nifurtimox eflornithine combination therapy in late-stage HAT patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Fexinidazole is a 5-nitroimidazole drug currently in clinical development for the treatment of human sleeping sickness (human African trypanosomiasis [HAT]), caused by infection with species of the protozoan parasite Trypanosoma brucei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21911566", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 357, "text": "In the search for new therapeutics, the repurposing of the broad-spectrum antiprotozoal drug fexinidazole has completed Phase III trials with the anticipation that it will be the first oral treatment for HAT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28552771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND AND OBJECTIVES Fexinidazole is a 5-nitroimidazole recently included in a clinical efficacy trial as an oral drug for the treatment of human African trypanosomiasis (HAT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24535888", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 869, "text": "Fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining of public and pharmaceutical company databases, has the potential to become a short-course, safe and effective oral treatment, curing both acute and chronic HAT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22539226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Fexinidazole: a potential new drug candidate for Chagas disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133682", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Antitrypanosomal activity of fexinidazole metabolites, potential new drug candidates for Chagas disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24841257", "endSection": "title" } ] }, { "body": "Is Tocilizumab effective for Giant-Cell Arteritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27182063", "http://www.ncbi.nlm.nih.gov/pubmed/27927642", "http://www.ncbi.nlm.nih.gov/pubmed/24075627", "http://www.ncbi.nlm.nih.gov/pubmed/29146018", "http://www.ncbi.nlm.nih.gov/pubmed/28745999", "http://www.ncbi.nlm.nih.gov/pubmed/28499892", "http://www.ncbi.nlm.nih.gov/pubmed/28116918", "http://www.ncbi.nlm.nih.gov/pubmed/26885650", "http://www.ncbi.nlm.nih.gov/pubmed/27919193", "http://www.ncbi.nlm.nih.gov/pubmed/24854376", "http://www.ncbi.nlm.nih.gov/pubmed/24357324", "http://www.ncbi.nlm.nih.gov/pubmed/28895041", "http://www.ncbi.nlm.nih.gov/pubmed/28138903" ], "ideal_answer": [ "Yes, Tocilizumab effective for Giant-Cell Arteritis. Its efficacy was proven in clinical trials. Tocilizumab may exert its therapeutic effects in Giant-Cell Arteritis by increasing the proliferation and activation of Tregs, and by reverting the pathogenic Treg phenotype seen during active disease." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D013700" ], "type": "yesno", "id": "5a733d2a2dc08e987e000015", "snippets": [ { "offsetInBeginSection": 1734, "offsetInEndSection": 1957, "text": "Emerging evidence for adjunctive therapy with tocilizumab, methotrexate, aspirin, angiotensin receptor blockers, and statins is encouraging and may lead to a more mainstream role for these therapies among patients with GCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28138903", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 914, "text": " TNF-\u03b1 blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "OBJECTIVES: Randomised-controlled trials have recently proven the efficacy of the interleukin (IL)-6 receptor antagonist tocilizumab (TCZ) in giant cell arteritis (GCA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27927642", "endSection": "abstract" }, { "offsetInBeginSection": 1672, "offsetInEndSection": 1861, "text": "CONCLUSIONS: TCZ may exert its therapeutic effects in GCA by increasing the proliferation and activation of Tregs, and by reverting the pathogenic Treg phenotype seen during active disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27927642", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 769, "text": "Cyclophosphamide and tocilizumab look promising but require validation in further studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27919193", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1440, "text": "Therefore, tocilizumab (humanised monoclonal antibody binding the human interleukin-6 receptor) was introduced as a potential salvage therapy with a swift consecutive resolution of the systemic symptoms and stabilization of the ophthalmic lesions.CONCLUSIONS: Although a late effect of steroids pulses cannot be formally ruled out in this dramatic situation, tocilizumab likely offered a decisive effect in preventing bilateral blindness and may have contributed to steroid tapering. Tocilizumab may represent a new early effective second-line treatment option in corticosteroid-resistant anterior ischemic optic neuropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28499892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Tocilizumab for giant cell arteritis with corticosteroid-resistant progressive anterior ischemic optic neuropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28499892", "endSection": "title" }, { "offsetInBeginSection": 2203, "offsetInEndSection": 2573, "text": "CONCLUSIONS: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28745999", "endSection": "abstract" }, { "offsetInBeginSection": 1098, "offsetInEndSection": 1234, "text": "Two RCTs have evidenced the efficacy of tocilizumab in addition to glucocorticoids (GCs) in the treatment of giant cell arteritis (GCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28895041", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 1001, "text": " Recent randomized placebo-controlled trials have reported on the efficacy and safety of abatacept and mostly tocilizumab in inducing and maintaining remission of GCA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29146018", "endSection": "abstract" }, { "offsetInBeginSection": 1307, "offsetInEndSection": 1490, "text": "If a biological therapy is indicated, and in light of the data discussed in this review, the first choice would be tocilizumab in GCA and anti-TNF-\u03b1 agents (mainly infliximab) in TAK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29146018", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 537, "text": "CONCLUSION: TCZ is effective in GCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27182063", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 920, "text": "TNF-\u03b1 blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116918", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 621, "text": "A favorable outcome was rapidly observed both on clinical and biological data allowing a corticoid therapy sparing.
CONCLUSION: Tocilizumab is a promising treatment of giant cell arteritis but controlled trials are needed to confirm its efficacy.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 360, "text": "INTRODUCTION: Treatment of giant cell arteritis is based on prolonged corticosteroid therapy but adverse side effects are common especially in the elderly.
CASE REPORTS: We report three patients with giant cell vasculitis treated by tocilizumab, an interleukin-6 receptor antibody, owing to resistance or intolerance to corticosteroid therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075627", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 668, "text": "Several studies have reported that tocilizumab is effective for aortitis associated with Takayasu's arteritis and giant cell arteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24357324", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 900, "text": "TNF-\u03b1 blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116918", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 515, "text": "Preliminary clinical trial data suggest that abatacept and tocilizumab reduce the risk of relapse in GCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26885650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Tocilizumab, an effective treatment for relapsing giant cell arteritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24854376", "endSection": "title" }, { "offsetInBeginSection": 718, "offsetInEndSection": 899, "text": "TNF-\u03b1 blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116918", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 551, "text": "Tocilizumab is a promising treatment of giant cell arteritis but controlled trials are needed to confirm its efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075627", "endSection": "abstract" } ] }, { "body": "Is there a link between nuclear position and DNA repair pathway choice?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25366693" ], "ideal_answer": [ "Yes. Nuclear position dictates DNA repair pathway choice, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D045643", "https://meshb.nlm.nih.gov/record/ui?ui=D059767", "https://meshb.nlm.nih.gov/record/ui?ui=D004260" ], "type": "yesno", "id": "5a774e40faa1ab7d2e000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Nuclear position dictates DNA repair pathway choice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366693", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 1137, "text": "We demonstrate that DSBs induced at the nuclear membrane (but not at nuclear pores or nuclear interior) fail to rapidly activate the DNA damage response (DDR) and repair by homologous recombination (HR). Real-time and superresolution imaging reveal that DNA DSBs within lamina-associated domains do not migrate to more permissive environments for HR, like the nuclear pores or the nuclear interior, but instead are repaired in situ by alternative end-joining. Our results are consistent with a model in which nuclear position dictates the choice of DNA repair pathway, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366693", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1137, "text": "Our results are consistent with a model in which nuclear position dictates the choice of DNA repair pathway, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Nuclear position dictates DNA repair pathway choice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366693", "endSection": "title" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1138, "text": "Our results are consistent with a model in which nuclear position dictates the choice of DNA repair pathway, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366693", "endSection": "abstract" } ] }, { "body": "Can non ubiquitinated Tomm20 promote mitophagy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27503909" ], "ideal_answer": [ "The translocase of outer mitochondrial membrane 20 (Tomm20), is a mitochondrial translocase that, when ubiquitinated, promotes mitophagy. " ], "exact_answer": "no", "type": "yesno", "id": "5a992eac1d1251d03b00000c", "snippets": [ { "offsetInBeginSection": 1128, "offsetInEndSection": 1549, "text": " A total of 338 new targets were identified and from these we validated glycogen synthase kinase 3\u03b2 (Gsk3\u03b2), which can phosphorylate \u03b1-synuclein, and translocase of outer mitochondrial membrane 20 (Tomm20), a mitochondrial translocase that, when ubiquitinated, promotes mitophagy, as SCFFbxo7substrates both in vitro and in vivo Ubiquitin chain restriction analyses revealed that Fbxo7 modified Gsk3\u03b2 using K63 linkages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27503909", "endSection": "abstract" } ] }, { "body": "Does SARM1 deletion cause neurodegeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26820848" ], "ideal_answer": [ "Mouse strain with Sarm1 deletion (Sarm1-/-) is highly resistant to axon neurodegeneration." ], "exact_answer": "no", "type": "yesno", "id": "5a9931cd1d1251d03b00000d", "snippets": [ { "offsetInBeginSection": 1168, "offsetInEndSection": 1509, "text": "Finally, using neurons from two distinct mutant mouse strains whose axons are highly resistant to neurodegeneration (Wld(S) and Sarm1(-/-)), we found that the three different fibrils were secreted by axons after anterograde transport, in the absence of axonal lysis, indicating that trans-neuronal spread can occur in intact healthy neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26820848", "endSection": "abstract" } ] }, { "body": "Is DNA polymerase \u03b8 involved in DNA repair?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25775267", "http://www.ncbi.nlm.nih.gov/pubmed/28668117", "http://www.ncbi.nlm.nih.gov/pubmed/25851856", "http://www.ncbi.nlm.nih.gov/pubmed/28459528" ], "ideal_answer": [ "Yes, \tDNA polymerase \u03b8 protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks." ], "exact_answer": "yes", "type": "yesno", "id": "5aacd38efcf4565872000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "DNA polymerase \u03b8 (Pol \u03b8) is implicated in various cellular processes including double-strand break repair and apurinic/apyrimidinic site bypass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459528", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 245, "text": " Pol \u03b8 is the defining enzyme for a pathway of DSB repair termed \"alternative end-joining\" (altEJ) or \"theta-mediated end-joining.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28668117", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 186, "text": "DNA polymerase \u03b8 is a key player in PARP-mediated DNA damage repair and essential for the survival of cancer cells where homologous recombination is compromised. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25851856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "DNA polymerase \u03b8 protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25775267", "endSection": "abstract" } ] }, { "body": "List drugs that are included in the Vosevi polypill.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29059462" ], "ideal_answer": [ "Vosevi pill includes sofosbuvir, velpatasvir and voxilaprevir. It is approved by the US Food and Drug Administration (FDA) for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have: genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor; and genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor." ], "exact_answer": [ [ "sofosbuvir" ], [ "velpatasvir" ], [ "voxilaprevir" ] ], "type": "list", "id": "5a7339372dc08e987e000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 588, "text": "On July 18, 2017, the US Food and Drug Administration (FDA) approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed-dose combination (FDC), an interferon-free, complete regimen for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have: genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor; and genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059462", "endSection": "abstract" } ] }, { "body": "What part of what body organ controls the circadian clock?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28707700", "http://www.ncbi.nlm.nih.gov/pubmed/28285822", "http://www.ncbi.nlm.nih.gov/pubmed/17517647", "http://www.ncbi.nlm.nih.gov/pubmed/20174808", "http://www.ncbi.nlm.nih.gov/pubmed/28596466", "http://www.ncbi.nlm.nih.gov/pubmed/25512305", "http://www.ncbi.nlm.nih.gov/pubmed/12505612", "http://www.ncbi.nlm.nih.gov/pubmed/28232786", "http://www.ncbi.nlm.nih.gov/pubmed/26332965", "http://www.ncbi.nlm.nih.gov/pubmed/26453621", "http://www.ncbi.nlm.nih.gov/pubmed/23604475", "http://www.ncbi.nlm.nih.gov/pubmed/28286126", "http://www.ncbi.nlm.nih.gov/pubmed/25645021", "http://www.ncbi.nlm.nih.gov/pubmed/23704227", "http://www.ncbi.nlm.nih.gov/pubmed/21969583" ], "ideal_answer": [ "the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the central clock in mammals, the circadian expression of clock genes ", "The mammalian circadian system is composed of a hierarchical multi-oscillator structure, with the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus in the brain" ], "exact_answer": [ "suprachiasmatic nucleus (SCN) of the hypothalamus in the brain" ], "type": "factoid", "id": "5a95765bfcd1d6a10c000028", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 142, "text": "the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the central clock in mammals, the circadian expression of clock genes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28232786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is the site of the main circadian clock", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28286126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The suprachiasmatic nucleus (SCN) of the hypothalamus orchestrates daily rhythms of physiology and behavior in mammals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28285822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The suprachiasmatic nucleus houses the central circadian clock and is characterized by the timely regulated expression of clock genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28707700", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 736, "text": "Clock genes control circadian rhythms both centrally, in the suprachiasmatic nucleus of the brain and peripherally, within every organ of the body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23704227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "The mammalian circadian system consists of a central oscillator in the suprachiasmatic nucleus of the hypothalamus, which coordinates peripheral clocks in organs throughout the body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17517647", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 450, "text": "The central clock in the suprachiasmatic nucleus (SCN) has been well studied, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25512305", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 319, "text": " In mammals, a master clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, adjusts timing of other self-sustained oscillators in the brain and peripheral organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20174808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Circadian clocks are endogenous and biological oscillations that occur with a period of<24\u2005h. In mammals, the central circadian pacemaker is localized in the suprachiasmatic nucleus (SCN) and is linked to peripheral tissues through neural and hormonal signals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26453621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "The suprachiasmatic nucleus (SCN) controls circadian rhythms in mammals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12505612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The environmental light-dark (LD) cycle entrains the central circadian clock located in the suprachiasmatic nucleus (SCN) of mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25645021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Although circadian rhythms in mammalian physiology and behavior are dependent upon a biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus, the molecular mechanism of this clock is in fact cell autonomous and conserved in nearly all cells of the body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23604475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The mammalian circadian timing system consists of a central pacemaker in the brain's suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26332965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The suprachiasmatic nucleus of the brain is the circadian center, relaying rhythmic environmental and behavioral information to peripheral tissues to control circadian physiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21969583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The nerve center responsible for controlling our circadian rhythm is located in a cluster of cells known as the suprachiasmatic nucleus in the hypothalamus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28596466", "endSection": "abstract" } ] }, { "body": "Which algorithms are used for compression of SAM files?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23066097", "http://www.ncbi.nlm.nih.gov/pubmed/29046896", "http://www.ncbi.nlm.nih.gov/pubmed/22164252", "http://www.ncbi.nlm.nih.gov/pubmed/26026138", "http://www.ncbi.nlm.nih.gov/pubmed/27540265" ], "ideal_answer": [ "The most popular format for genomic data is the SAM (Sequence Alignment/Map) format, which contains information such as alignment, quality values, etc. These files are large (on the order of terabytes), which necessitates compression. GeneComp, NGC, SAMZIP and QVZ are algorithms which perform compression of data stored in SAM files." ], "exact_answer": [ [ "GeneComp" ], [ "NGC" ], [ "SAMZIP" ], [ "QVZ" ], [ "CSAM" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000465", "https://meshb.nlm.nih.gov/record/ui?ui=D044962" ], "type": "list", "id": "5a76344e9e632bc066000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "GeneComp, a new reference-based compressor for SAM files", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29046896", "endSection": "title" }, { "offsetInBeginSection": 138, "offsetInEndSection": 888, "text": "The most popular format for genomic data is the SAM format, which contains information such as alignment, quality values, etc. These files are large (on the order of terabytes), which necessitates compression. In this work we propose a new reference-based compressor for SAM files, which can accommodate different levels of compression, based on the specific needs of the user. In particular, the proposed compressor GeneComp allows the user to perform lossy compression of the quality scores, which have been proven to occupy more than half of the compressed file (when losslessly compressed). We show that the proposed compressor GeneComp overall achieves better compression ratios than previously proposed algorithms when working on lossless mode.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29046896", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 1291, "text": "The enormous size of these data motivates the development of data compression algorithms usable for the implementation of the various storage policies that are applied to the produced intermediate and final result files. In this article, we present NGC, a tool for the compression of mapped short read data stored in the wide-spread SAM format. NGC enables lossless and lossy compression and introduces the following two novel ideas: first, we present a way to reduce the number of required code words by exploiting common features of reads mapped to the same genomic positions; second, we present a highly configurable way for the quantization of per-base quality values, which takes their influence on downstream analyses into account. NGC, evaluated with several real-world data sets, saves 33-66% of disc space using lossless and up to 98% disc space using lossy compression. By applying two popular variant and genotype prediction tools to the decompressed data, we could show that the lossy compression modes preserve>99% of all called variants while outperforming comparable methods in some configurations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23066097", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 638, "text": "Research in bioinformatics primarily involves collection and analysis of a large volume of genomic data. Naturally, it demands efficient storage and transfer of this huge amount of data. In recent years, some research has been done to find efficient compression algorithms to reduce the size of various sequencing data. One way to improve the transmission time of large files is to apply a maximum lossless compression on them. In this paper, we present SAMZIP, a specialized encoding scheme, for sequence alignment data in SAM (Sequence Alignment/Map) format, which improves the compression ratio of existing compression tools available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22164252", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1119, "text": "Recent advancements in sequencing technology have led to a drastic reduction in the cost of sequencing a genome. This has generated an unprecedented amount of genomic data that must be stored, processed and transmitted. To facilitate this effort, we propose a new lossy compressor for the quality values presented in genomic data files (e.g. FASTQ and SAM files), which comprise roughly half of the storage space (in the uncompressed domain). Lossy compression allows for compression of data beyond its lossless limit.RESULTS: The proposed algorithm QVZ exhibits better rate-distortion performance than the previously proposed algorithms, for several distortion metrics and for the lossless case. Moreover, it allows the user to define any quasi-convex distortion function to be minimized, a feature not supported by the previous algorithms. Finally, we show that QVZ-compressed data exhibit better performance in the genotyping than data compressed with previously proposed algorithms, in the sense that for a similar rate, a genotyping closer to that achieved with the original quality values is obtained.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26026138", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 638, "text": "In this paper, we present SAMZIP, a specialized encoding scheme, for sequence alignment data in SAM (Sequence Alignment/Map) format, which improves the compression ratio of existing compression tools available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22164252", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 465, "text": "We describe CSAM (Compressed SAM format), a compression approach offering lossless and lossy compression for SAM files.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27540265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "GeneComp, a new reference-based compressor for SAM files.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29046896", "endSection": "title" } ] }, { "body": "What does MetaHIT stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23431991" ], "ideal_answer": [ "Metagenomics of the Human Intestinal Tract (MetaHIT) project are focusing mainly on the human microbiome" ], "exact_answer": [ "Metagenomics of the Human Intestinal Tract" ], "type": "factoid", "id": "5a992b371d1251d03b00000a", "snippets": [ { "offsetInBeginSection": 459, "offsetInEndSection": 689, "text": "The importance of microbiome constituency is so relevant that several consortia like the Human Microbiome project (HMP) and Metagenomics of the Human Intestinal Tract (MetaHIT) project are focusing mainly on the human microbiome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23431991", "endSection": "abstract" } ] }, { "body": "List 4 drugs used to treat opioid addiction or overdose", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26808307", "http://www.ncbi.nlm.nih.gov/pubmed/28358791", "http://www.ncbi.nlm.nih.gov/pubmed/12738346", "http://www.ncbi.nlm.nih.gov/pubmed/28132694", "http://www.ncbi.nlm.nih.gov/pubmed/16953647", "http://www.ncbi.nlm.nih.gov/pubmed/28292795", "http://www.ncbi.nlm.nih.gov/pubmed/28203387", "http://www.ncbi.nlm.nih.gov/pubmed/19926374", "http://www.ncbi.nlm.nih.gov/pubmed/25271657" ], "ideal_answer": [ "Suboxone (buprenorphine/naloxone) and methadone are used to assist in opioid withdrawal and Naloxone is used to treat overdoses" ], "exact_answer": [ [ "methadone" ], [ "naloxone" ], [ "suboxone" ], [ "buprenorphine" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D062787", "https://meshb.nlm.nih.gov/record/ui?ui=D000073316" ], "type": "list", "id": "5aa13fd3d6d6b54f79000003", "snippets": [ { "offsetInBeginSection": 580, "offsetInEndSection": 752, "text": "Currently, the American College of Obstetricians and Gynecologists recommends methadone, buprenorphine, or buprenorphine/naloxone in the treatment of prenatal opioid abuse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28203387", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 411, "text": "PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28292795", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 342, "text": "Methadone is an opioid prescribed for pain management and is also provided through opioid treatment programs to treat opioid use disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28358791", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 265, "text": "Fortunately, there are effective medications (ie, methadone, buprenorphine, and oral and injectable naltrexone) available for the treatment of opioid addiction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26808307", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 577, "text": " We describe the major classes of drug treatments available, including opioid agonist (e.g., methadone, buprenorphine, LAAM), antagonist (e.g., naltrexone)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19926374", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1384, "text": "he development of buprenorphine, a partial opioid agonist, as an effective treatment for opioid addiction reopened the possibility for having a less burdensome oversight process,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12738346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Although the synthetic opioid buprenorphine has been available clinically for almost 30 years, its use has only recently become much more widespread for the treatment of opioid addiction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16953647", "endSection": "abstract" } ] }, { "body": "Can nanoparticles be used for afterglow imaging?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28657119" ], "ideal_answer": [ "Nanoparticles are used for afterglow imaging." ], "exact_answer": "yes", "type": "yesno", "id": "5a992d981d1251d03b00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Ultralong Phosphorescence of Water-Soluble Organic Nanoparticles for In Vivo Afterglow Imaging", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657119", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, and proof-of-concept application of organic semiconducting nanoparticles (OSNs) with ultralong phosphorescence for in vivo afterglow imaging. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657119", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1246, "text": "This study not only introduces the first category of water-soluble ultralong phosphorescence organic nanoparticles but also reveals a universal design principle to prolong the lifetime of phosphorescent molecules to the level that can be effective for molecular imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657119", "endSection": "abstract" } ] }, { "body": "Describe mechanism of action of Romosozumab.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28064540", "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "http://www.ncbi.nlm.nih.gov/pubmed/28428078", "http://www.ncbi.nlm.nih.gov/pubmed/28246926", "http://www.ncbi.nlm.nih.gov/pubmed/27569204", "http://www.ncbi.nlm.nih.gov/pubmed/26277199", "http://www.ncbi.nlm.nih.gov/pubmed/27487526", "http://www.ncbi.nlm.nih.gov/pubmed/28529724", "http://www.ncbi.nlm.nih.gov/pubmed/27865001", "http://www.ncbi.nlm.nih.gov/pubmed/24835636", "http://www.ncbi.nlm.nih.gov/pubmed/28458516", "http://www.ncbi.nlm.nih.gov/pubmed/26451332" ], "ideal_answer": [ "Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. In the presence of romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain. It is used for osteoporosis treatment." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D045504" ], "type": "summary", "id": "5a723a652dc08e987e00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on bone by increasing bone formation and reducing bone resorption, and thus has favorable effects in both aspects of bone volume regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27487526", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 361, "text": "Romosozumab is a humanized monoclonal antibody to sclerostin that binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density (BMD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28064540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Romosozumab (Romo), a humanized sclerostin antibody, is a bone-forming agent under development for treatment of osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27865001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Treatment with sclerostin antibody (romosozumab) increases bone formation while reducing bone resorption, leading to increases in bone volume and bone mineral density. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28246926", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 596, "text": "Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. Therefore, in the presence of romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28458516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Romosozumab, a humanized monoclonal sclerostin antibody under development for the treatment of osteoporosis, has a unique mechanism of action on bone-increasing bone formation and decreasing bone resorption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28428078", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1368, "text": "Romosozumab, an anti-sclerosin antibody, and abaloparatide, a PTH-related peptide analog, are at present in advanced stages of clinical evaluation, so far demonstrating efficaciousness together with a favorable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26277199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Update on romosozumab : a humanized monoclonal antibody to sclerostin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "title" }, { "offsetInBeginSection": 329, "offsetInEndSection": 457, "text": "Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28458516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Romosozumab is a humanized immunoglobulin G2 monoclonal antibody that binds and blocks the action of sclerostin, a protein secreted by the osteocyte and an extracellular inhibitor of canonical Wnt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569204", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 347, "text": "Romosozumab is a humanized monoclonal antibody to sclerostin that binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density (BMD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28064540", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1025, "text": "EXPERT OPINION Blocking sclerostin action with romosozumab is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis; efficacy and safety data on large controlled studies are awaited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 652, "text": "AREAS COVERED Romosozumab is the first humanized monoclonal sclerostin antibody to be tested in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 285, "text": "Romosozumab is a humanized monoclonal antibody targeting sclerostin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24835636", "endSection": "abstract" }, { "offsetInBeginSection": 1472, "offsetInEndSection": 1645, "text": "Romosozumab, an anti-sclerostin antibody, inhibits the action of sclerostin, a canonical Wnt signal inhibitor secreted from osteocytes, and enhances canonical Wnt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28529724", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 464, "text": "A pharmacokinetic model with first-order absorption and dual elimination pathways was used to describe the kinetics of romosozumab, a monoclonal antibody (mAb) against sclerostin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26451332", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 816, "text": "Similar to preclinical animal studies with sclerostin antibodies, initial clinical studies show that romosozumab increases bone formation and bone mineral density.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665957", "endSection": "abstract" } ] }, { "body": "Which proteins are regulated by Nrf2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27308893", "http://www.ncbi.nlm.nih.gov/pubmed/26846360", "http://www.ncbi.nlm.nih.gov/pubmed/27369375", "http://www.ncbi.nlm.nih.gov/pubmed/27278863", "http://www.ncbi.nlm.nih.gov/pubmed/27507633" ], "ideal_answer": [ "Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects cells from oxidative stress through induction of various antioxidant enzymes." ], "type": "summary", "id": "5aa82388fcf4565872000001", "snippets": [ { "offsetInBeginSection": 124, "offsetInEndSection": 168, "text": "stress-responsive transcription factors Nrf2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27278863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Nuclear Factor E2-Related Factor-2 Negatively Regulates NLRP3 Inflammasome Activity by Inhibiting Reactive Oxygen Species-Induced NLRP3 Priming.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27308893", "endSection": "title" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1164, "text": " Nrf2-regulated targets, including glutathione reductase, glutathione S-transferase, and NAD(P)H quinone oxidoreductase-1 (NQO1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27369375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Nuclear factor erythroid 2-related factor 2 (Nrf2) is a neuroprotective transcription factor that has recently attracted increased attention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26846360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects cells from oxidative stress through induction of various antioxidant enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27507633", "endSection": "abstract" } ] }, { "body": "What drug cures hepatitis C?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26085900", "http://www.ncbi.nlm.nih.gov/pubmed/26209383" ], "ideal_answer": [ "Sofosbuvir-based therapy cures hepatitis C virus infection" ], "exact_answer": [ "Sofosbuvir based therapy" ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:1883", "https://meshb.nlm.nih.gov/record/ui?ui=D006526" ], "type": "factoid", "id": "5aa3fb7ad6d6b54f79000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Sofosbuvir-based therapy cures hepatitis C virus infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26209383", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Sofosbuvir-based therapy cures hepatitis c virus infection after prior treatment failures in a patient with concurrent lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26209383", "endSection": "title" }, { "offsetInBeginSection": 430, "offsetInEndSection": 548, "text": "The emerging archetypal example is the outcry over the cost of sofosbuvir, a drug proved to cure hepatitis C infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26085900", "endSection": "abstract" } ] }, { "body": "Is there any role of interleukin-11 in cardiovascular fibrosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29160304" ], "ideal_answer": [ "Yes. Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect. IL11 and its receptor (IL11RA) are expressed specifically in fibroblasts where they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure whereas genetic deletion of Il11ra1 is protective against disease. Thus, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D005355", "https://meshb.nlm.nih.gov/record/ui?ui=D017370" ], "type": "yesno", "id": "5a8b292afcd1d6a10c00001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "IL11 is a crucial determinant of cardiovascular fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29160304", "endSection": "title" }, { "offsetInBeginSection": 492, "offsetInEndSection": 1380, "text": "Using integrated imaging-genomics analyses of primary human fibroblasts, we found that Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect. IL11 and its receptor (IL11RA) are expressed specifically in fibroblasts where they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure whereas genetic deletion of Il11ra1 is protective against disease. Thus, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These data reveal a central role of IL11 in fibrosis and we propose inhibition of IL11 as a new therapeutic strategy to treat fibrotic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29160304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "IL11 is a crucial determinant of cardiovascular fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29160304", "endSection": "title" } ] }, { "body": "List major risk factors for Alzheimer's disease. ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28884281", "http://www.ncbi.nlm.nih.gov/pubmed/28396259", "http://www.ncbi.nlm.nih.gov/pubmed/28435465", "http://www.ncbi.nlm.nih.gov/pubmed/28272510", "http://www.ncbi.nlm.nih.gov/pubmed/27300264" ], "ideal_answer": [ "Apolipoprotein E4\ntype 2 diabetes\nClusterin\nHypertension\nadvancing age\nobesity" ], "exact_answer": [ [ "Apolipoprotein E4" ], [ "type 2 diabetes" ], [ "Clusterin" ], [ "Hypertension" ], [ "advancing age" ], [ "obesity" ] ], "type": "list", "id": "5a9d96564e03427e73000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer's disease (AD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28272510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28435465", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 372, "text": "Clusterin (Apo J) is one of the major risk factors for sporadic form of AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28396259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Hypertension is one of the major risk factors for central nervous system (CNS) disorders like stroke and Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884281", "endSection": "abstract" }, { "offsetInBeginSection": 57, "offsetInEndSection": 186, "text": "Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27300264", "endSection": "abstract" } ] }, { "body": "What can be predicted with the Wells criteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28969751", "http://www.ncbi.nlm.nih.gov/pubmed/15520710", "http://www.ncbi.nlm.nih.gov/pubmed/28970024", "http://www.ncbi.nlm.nih.gov/pubmed/27689922", "http://www.ncbi.nlm.nih.gov/pubmed/25763885", "http://www.ncbi.nlm.nih.gov/pubmed/26559176", "http://www.ncbi.nlm.nih.gov/pubmed/28236025" ], "ideal_answer": [ "Wells criteria are used to determine clinical probability of pulmonary embolism." ], "exact_answer": [ "pulmonary embolism" ], "type": "factoid", "id": "5a7428090384be9551000001", "snippets": [ { "offsetInBeginSection": 220, "offsetInEndSection": 725, "text": "Materials and Methods This HIPAA-compliant, institutional review board-approved study was performed at a tertiary care, academic medical center ED with approximately 60 000 annual visits and included all patients who were suspected of having pulmonary embolism (PE) and who underwent CT pulmonary angiography between January 1, 2011, and August 31, 2013. The requirement to obtain informed consent was waived. Each CT order for pulmonary angiography was exposed to CDS on the basis of the Wells criteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27689922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Incremental diagnostic quality gain of CTA over V/Q scan in the assessment of pulmonary embolism by means of a Wells score Bayesian model: results from the ACDC collaboration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28236025", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "OBJECTIVE: Our objective was to evaluate the diagnostic value of computed tomography angiography (CTA) and ventilation perfusion (V/Q) scan in the assessment of pulmonary embolism (PE) by means of a Bayesian statistical model.METHODS: Wells criteria defined pretest probability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28236025", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 867, "text": " As her immediate risk of VTE was low (Wells criteria), she was advised mechanical measures to prevent VTE along with continuation of rivaroxaban therapy which had already been prescribed for her avalvular atrial fibrillation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28969751", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 585, "text": " For ED patients aged 18+years with suspected PE, CTPE use and yield were compared 19months pre- and 32months post-implementation of CDS intervention based on the Wells criteria, provided at the time of CTPE order, deployed in April 2012. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28970024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Correlation between the Wells score and the Quanadli index in patients with pulmonary embolism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25763885", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND AND AIMS: Determining clinical probability of pulmonary embolism (PE) with Wells scoring system is the first step towards diagnosis of PE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25763885", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 510, "text": "Clinical probability of PE was determined according to the Wells and modified Wells scoring system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25763885", "endSection": "abstract" }, { "offsetInBeginSection": 1628, "offsetInEndSection": 1725, "text": "CONCLUSION: Modified Wells criteria have high sensitivity but low specificity in PE diagnostics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25763885", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 859, "text": "METHODS: This was a prospective investigation of the sensitivity of multidetector CTPA among patients with a priori clinical assessment of a high probability of PE according to the Wells criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26559176", "endSection": "abstract" }, { "offsetInBeginSection": 1658, "offsetInEndSection": 1827, "text": "When Wells Criteria were dichotomized into pulmonary embolism-unlikely (n=88, 66%) or pulmonary embolism-likely (n=46, 34%), the prevalence was 3% and 28%, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520710", "endSection": "abstract" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1657, "text": "When Wells Criteria were trichotomized into low pretest probability (n=59, 44%), moderate pretest probability (n=61, 46%), or high pretest probability (n=14, 10%), the pulmonary embolism prevalence was 2%, 15%, and 43%, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520710", "endSection": "abstract" }, { "offsetInBeginSection": 1828, "offsetInEndSection": 2166, "text": "The immunoturbidimetric and rapid enzyme-linked immunosorbent assay d -dimer assays had similar sensitivities (94%) and specificities (45% versus 46%).
CONCLUSION: Wells Criteria have a moderate to substantial interrater agreement and reliably risk stratify pretest probability in patients with suspected pulmonary embolism.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15520710", "endSection": "title" } ] }, { "body": "What is the purpose of the Tabix tool?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21208982" ], "ideal_answer": [ "Tabix is the first generic tool that indexes position sorted files in TAB-delimited formats such as GFF, BED, PSL, SAM and SQL export, and quickly retrieves features overlapping specified regions. Tabix features include few seek function calls per query, data compression with gzip compatibility and direct FTP/HTTP access. Tabix is implemented as a free command-line tool as well as a library in C, Java, Perl and Python. It is particularly useful for manually examining local genomic features on the command line and enables genome viewers to support huge data files and remote custom tracks over networks.", "Tabix is the first generic tool that indexes position sorted files in tab-delimited formats such as gff , bed , psl , sam and sql export , and quickly retrieves features overlapping specified regions . Tabix is implemented as a free command-line tool as well as a library in c , java , perl and python ." ], "type": "summary", "id": "5a7633a89e632bc066000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Tabix: fast retrieval of sequence features from generic TAB-delimited files.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 620, "text": "Tabix is the first generic tool that indexes position sorted files in TAB-delimited formats such as GFF, BED, PSL, SAM and SQL export, and quickly retrieves features overlapping specified regions. Tabix features include few seek function calls per query, data compression with gzip compatibility and direct FTP/HTTP access. Tabix is implemented as a free command-line tool as well as a library in C, Java, Perl and Python. It is particularly useful for manually examining local genomic features on the command line and enables genome viewers to support huge data files and remote custom tracks over networks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "UNLABELLED: Tabix is the first generic tool that indexes position sorted files in TAB-delimited formats such as GFF, BED, PSL, SAM and SQL export, and quickly retrieves features overlapping specified regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "UNLABELLED Tabix is the first generic tool that indexes position sorted files in TAB-delimited formats such as GFF, BED, PSL, SAM and SQL export, and quickly retrieves features overlapping specified regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 334, "text": "Tabix features include few seek function calls per query, data compression with gzip compatibility and direct FTP/HTTP access.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 342, "text": "Tabix features include few seek function calls per query, data compression with gzip compatibility and direct FTP/HTTP access.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Tabix: fast retrieval of sequence features from generic TAB-delimited files.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "title" }, { "offsetInBeginSection": 324, "offsetInEndSection": 422, "text": "Tabix is implemented as a free command-line tool as well as a library in C, Java, Perl and Python.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Tabix is the first generic tool that indexes position sorted files in TAB-delimited formats such as GFF, BED, PSL, SAM and SQL export, and quickly retrieves features overlapping specified regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 323, "text": "Tabix features include few seek function calls per query, data compression with gzip compatibility and direct FTP/HTTP access.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208982", "endSection": "abstract" } ] }, { "body": "What is MULTOVL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23071271" ], "ideal_answer": [ "MULTOVL is an application suite that detects and statistically analyses multiple overlaps of genomic regions in a fast and efficient manner. The package supports the detection of multiple region intersections, unions and 'solitary' genomic regions. The significance of actually observed overlaps is estimated by comparing them with empirical null distributions generated by random shuffling of the input regions." ], "type": "summary", "id": "5a76420c9e632bc066000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "MULTOVL: fast multiple overlaps of genomic regions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071271", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "We present the MULTOVL application suite that detects and statistically analyses multiple overlaps of genomic regions in a fast and efficient manner. The package supports the detection of multiple region intersections, unions and 'solitary' genomic regions. The significance of actually observed overlaps is estimated by comparing them with empirical null distributions generated by random shuffling of the input regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "We present the MULTOVL application suite that detects and statistically analyses multiple overlaps of genomic regions in a fast and efficient manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "MULTOVL: fast multiple overlaps of genomic regions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23071271", "endSection": "title" } ] }, { "body": "How is Hsd17b1 associated with endometriosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15640252", "http://www.ncbi.nlm.nih.gov/pubmed/19014997" ], "ideal_answer": [ "Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis. Inhibition of the estradiol-synthesizing enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has been proposed as a promising new therapeutic option to treat estrogen-dependent diseases like endometriosis" ], "type": "summary", "id": "5a99332a1d1251d03b00000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Association between endometriosis and genetic polymorphisms of the estradiol-synthesizing enzyme genes HSD17B1 and CYP19", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15640252", "endSection": "title" }, { "offsetInBeginSection": 134, "offsetInEndSection": 430, "text": "Here, we evaluated whether the risk and severity of endometriosis are associated with polymorphisms in estradiol-synthesizing enzyme genes: the Ser312Gly polymorphism in 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and the Arg264Cys polymorphism in cytochrome P450, subfamily XIX (CYP19)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15640252", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1154, "text": "Individuals having at least one A-allele (A/G or A/A genotype) of HSD17B1 showed a significantly increased risk of endometriosis (A/G genotype: adjusted OR, 3.06; 95%CI 1.21-7.74; A/A genotype: adjusted OR, 3.02; 95%CI 1.08-8.43). There was a significant trend associating A/G + A/A genotypes with severity of endometriosis (P for trend<0.01). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15640252", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1442, "text": "Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15640252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Lowering local estradiol concentration by inhibition of the estradiol-synthesizing enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has been proposed as a promising new therapeutic option to treat estrogen-dependent diseases like endometriosis and breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19014997", "endSection": "abstract" } ] }, { "body": "What is the drug Tecfidera used against?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24588595", "http://www.ncbi.nlm.nih.gov/pubmed/24259625", "http://www.ncbi.nlm.nih.gov/pubmed/26195059", "http://www.ncbi.nlm.nih.gov/pubmed/27226838" ], "ideal_answer": [ "Tecifidera is approved for the treatment of relapsing-remitting multiple sclerosis." ], "exact_answer": [ "Tecifidera is approved for the treatment of relapsing-remitting multiple sclerosis" ], "type": "factoid", "id": "5aa824a8fcf4565872000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Dimethyl fumarate (Tecfidera\u2122) is an effective therapy for relapsing forms of multiple sclerosis (MS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26195059", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 137, "text": "dimethyl fumarate (Tecfidera(\u00ae)) for multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27226838", "endSection": "title" }, { "offsetInBeginSection": 236, "offsetInEndSection": 318, "text": "Tecifidera is approved for the treatment of relapsing-remitting multiple sclerosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24588595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259625", "endSection": "title" } ] }, { "body": "Is there a disease or condition called Exploding Head Syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28622122", "http://www.ncbi.nlm.nih.gov/pubmed/24703829", "http://www.ncbi.nlm.nih.gov/pubmed/26252589", "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "http://www.ncbi.nlm.nih.gov/pubmed/1896728", "http://www.ncbi.nlm.nih.gov/pubmed/20726288", "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "http://www.ncbi.nlm.nih.gov/pubmed/11309216", "http://www.ncbi.nlm.nih.gov/pubmed/28385085", "http://www.ncbi.nlm.nih.gov/pubmed/2030791", "http://www.ncbi.nlm.nih.gov/pubmed/2769286", "http://www.ncbi.nlm.nih.gov/pubmed/23467433" ], "ideal_answer": [ "Exploding head syndrome (EHS) is characterized by loud noises or a sense of explosion in the head during sleep transitions." ], "exact_answer": "yes", "type": "yesno", "id": "5a8ee9d1fcd1d6a10c000027", "snippets": [ { "offsetInBeginSection": 146, "offsetInEndSection": 293, "text": "This case report describes the first-ever diagnosis of exploding head syndrome in a patient with longstanding epilepsy and novel nocturnal events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622122", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 134, "text": "Exploding head syndrome (EHS) is characterized by loud noises or a sense of explosion in the head during sleep transitions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28385085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Exploding head syndrome is characterized by the perception of loud noises during sleep-wake or wake-sleep transitions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 206, "text": "Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24703829", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 148, "text": "xploding head syndrome (EHS) is a rare parasomnia in which affected individuals awaken from sleep with the sensation of a loud bang. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23467433", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1272, "text": "Contrary to some earlier theorizing, exploding head syndrome was found to be a relatively common experience in younger individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Exploding head syndrome is characterized by the perception of loud noises during sleep-wake or wake-sleep transitions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Fifty patients suffering from the \"exploding head syndrome\" are described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2769286", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 375, "text": "In spite of the fact that its characteristic symptomatology was first described approximately 150 y ago, exploding head syndrome has received relatively little empirical and clinical attention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24703829", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 693, "text": "After first discussing the history, prevalence, and associated features, the available polysomnography data and five main etiological theories for exploding head syndrome are summarized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24703829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Exploding head syndrome: six new cases and review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Exploding Head Syndrome in the Epilepsy Monitoring Unit: Case Report and Literature Review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622122", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Exploding head syndrome: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23467433", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Exploding head syndrome is common in college students.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "title" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1141, "text": "Exploding head syndrome episodes were accompanied by clinically significant levels of fear, and a minority (2.80%) experienced it to such a degree that it was associated with clinically significant distress and/or impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Attention has recently been drawn to a condition termed the exploding head syndrome, which is characterized by unpleasant, even terrifying sensations of flashing lights and/or sounds during reported sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1896728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Exploding head syndrome is a rare phenomenon but can be a significant disruption to quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20726288", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 704, "text": "The rare headache disorder hypnic headache and the exploding head syndrome are also discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26252589", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 292, "text": "This case report describes the first-ever diagnosis of exploding head syndrome in a patient with longstanding epilepsy and novel nocturnal events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "BACKGROUND Exploding head syndrome (EHS) is characterized by attacks of a sudden noise or explosive feeling experienced in the head occurring during the transition from wake to sleep or from sleep to wake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "INTRODUCTION Exploding head syndrome (EHS) is a rare parasomnia in which affected individuals awaken from sleep with the sensation of a loud bang.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23467433", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1273, "text": "Contrary to some earlier theorizing, exploding head syndrome was found to be a relatively common experience in younger individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 210, "text": "This hitherto unreported syndrome is characterised by a sense of an explosive noise in the head usually in the twilight stage of sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2769286", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1070, "text": "EHS is a well-defined disease entity with a benign nature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24907167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Exploding head syndrome: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23467433", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Clinical features of the exploding head syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2769286", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Exploding head syndrome is common in college students.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773787", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The exploding head syndrome: polysomnographic recordings and therapeutic suggestions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1896728", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "This article reviews the features of an uncommon malady termed \"the exploding head syndrome.\" Sufferers describe terrorizing attacks of a painless explosion within their head", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11309216", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The case is reported of a 47-year old female suffering from the exploding head syndrome. This syndrome consists of a sudden awakening due to a loud noise shortly after falling asleep, sometimes accompanied by a flash of light.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2030791", "endSection": "abstract" } ] }, { "body": "What is INCB3619?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17363546", "http://www.ncbi.nlm.nih.gov/pubmed/16843264" ], "ideal_answer": [ "INCB3619, is avselective, potent, orally bioavailable small-molecule inhibitor of a subset of ADAM proteases that prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. Administration of INCB3619 to tumor-bearing mice reduced ErbB ligand shedding in vivo and inhibited ErbB pathway signaling (e.g., phosphorylation of Akt), tumor cell proliferation, and survival." ], "type": "summary", "id": "5a9d2a8f1d1251d03b000019", "snippets": [ { "offsetInBeginSection": 409, "offsetInEndSection": 661, "text": "A selective ADAM inhibitor, INCB3619, prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16843264", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1567, "text": "INCB3619 was identified as a representative selective, potent, orally bioavailable small-molecule inhibitor of a subset of ADAM proteases that block shedding of ErbB ligands. Administration of INCB3619 to tumor-bearing mice reduced ErbB ligand shedding in vivo and inhibited ErbB pathway signaling (e.g., phosphorylation of Akt), tumor cell proliferation, and survival. Further, INCB3619 synergized with clinically relevant cancer therapeutics and showed no overt or compounding toxicities, including fibroplasia, the dose-limiting toxicity associated with broad-spectrum matrix metalloprotease inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17363546", "endSection": "abstract" } ] }, { "body": "What is crenezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26467270" ], "ideal_answer": [ "Crenezumab is a humanized antibody targeting Amyloid-\u03b2 (A\u03b2) which is currently tested in multiple clinical trials for the prevention of Alzheimer's disease. It strongly reacts with amyloid plaques and detects N-terminally modified A\u03b2 peptides A\u03b24-42 and pyroglutamate A\u03b23-42." ], "type": "summary", "id": "5a9acc7b1d1251d03b000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Solanezumab and Crenezumab are two humanized antibodies targeting Amyloid-\u03b2 (A\u03b2) which are currently tested in multiple clinical trials for the prevention of Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26467270", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1159, "text": "Remarkably, Solanezumab showed a strong binding affinity to plaques. We also reaffirmed that Bapineuzumab does not recognize N-truncated or modified A\u03b2, while Solanezumab and Crenezumab do detect N-terminally modified A\u03b2 peptides A\u03b24-42 and pyroglutamate A\u03b23-42.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26467270", "endSection": "abstract" }, { "offsetInBeginSection": 1731, "offsetInEndSection": 1941, "text": "In conclusion, the biosimilar antibodies Solanezumab, Crenezumab and Bapineuzumab strongly react with amyloid plaques, which are in contrast to the NT4X antibody that hardly recognizes plaques in human tissue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26467270", "endSection": "abstract" } ] }, { "body": "Describe Vanishing lung syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24511405", "http://www.ncbi.nlm.nih.gov/pubmed/28219569", "http://www.ncbi.nlm.nih.gov/pubmed/28975065", "http://www.ncbi.nlm.nih.gov/pubmed/24977015", "http://www.ncbi.nlm.nih.gov/pubmed/26259424", "http://www.ncbi.nlm.nih.gov/pubmed/27695175", "http://www.ncbi.nlm.nih.gov/pubmed/25322795", "http://www.ncbi.nlm.nih.gov/pubmed/26770619", "http://www.ncbi.nlm.nih.gov/pubmed/19704328", "http://www.ncbi.nlm.nih.gov/pubmed/22937434" ], "ideal_answer": [ "Vanishing lung syndrome, also known as idiopathic giant bullous emphysema, is a rare disease characterized by giant emphysematous bullae. It is a rare radiological syndrome in which the lungs appear to be disappearing on X-ray. It typically occurs in young, thin male smokers with large bullae in one or more upper lobes occupying at least one-third of the hemithorax. This syndrome is associated with significant morbidity and mortality." ], "type": "summary", "id": "5a7376e33b9d13c708000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Vanishing lung syndrome is a clinical presentation of giant bullous emphysema associated with significant morbidity and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28219569", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 306, "text": "A small number of case reports have described a pathological entity called vanishing lung syndrome (VLS), which is a rare bullous lung disease usually caused by tobacco smoking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28975065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Giant bullous emphysema, or vanishing lung syndrome, typically occurs in young, thin male smokers with large bullae in one or more upper lobes occupying at least one-third of the hemithorax. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26770619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Vanishing lung syndrome, also known as idiopathic giant bullous emphysema, is a rare disease characterized by giant emphysematous bullae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25322795", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Vanishing lung syndrome (VLS) is a rare radiological syndrome in which the lungs appear to be disappearing on X-ray. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Giant bullous emphysema (GBE), known as 'vanishing lung syndrome', usually occurs in association with chronic obstructive pulmonary disease (COPD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24977015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Vanishing lung syndrome (VLS) is a rare and distinct clinical syndrome that usually affects young men. VLS leads to severe progressive dyspnea and is characterized by extensive, asymmetric, peripheral, and predominantly upper lobe giant lung bullae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24511405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "We describe here a rare case of Idiopathic Bullous Emphysema/Vanishing Lung Syndrome (VLS) in a 33-year-old male patient with a history of marijuana abuse who presents to the hospital with pleuritic chest pain thought to be due to pneumothorax based on the chest radiograph. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22937434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Vanishing lung syndrome (giant bullous emphysema): CT findings in 7 patients and a literature review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19704328", "endSection": "title" }, { "offsetInBeginSection": 695, "offsetInEndSection": 792, "text": "Eventually, his CT chest revealed the diagnosis of giant bullous disease/vanishing lung syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Vanishing lung syndrome (VLS) is a rare radiological syndrome in which the lungs appear to be disappearing on X-ray.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26259424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Vanishing lung syndrome, also known as idiopathic giant bullous emphysema, is a rare disease characterized by giant emphysematous bullae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25322795", "endSection": "abstract" } ] }, { "body": "What do the trispecific HIV antibodies target?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28931639" ], "ideal_answer": [ "Trispecific HIV antibodies (Abs) allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site." ], "exact_answer": [ [ "CD4 binding site" ], [ "membrane-proximal external region (MPER)" ], [ "V1V2 glycan site" ] ], "type": "list", "id": "5a9d2dd21d1251d03b00001a", "snippets": [ { "offsetInBeginSection": 175, "offsetInEndSection": 404, "text": "We engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931639", "endSection": "abstract" } ] }, { "body": "What is calciphylaxis", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26908770", "http://www.ncbi.nlm.nih.gov/pubmed/9426423", "http://www.ncbi.nlm.nih.gov/pubmed/20019019", "http://www.ncbi.nlm.nih.gov/pubmed/18045036", "http://www.ncbi.nlm.nih.gov/pubmed/23663061", "http://www.ncbi.nlm.nih.gov/pubmed/21410615", "http://www.ncbi.nlm.nih.gov/pubmed/18417747", "http://www.ncbi.nlm.nih.gov/pubmed/26779700", "http://www.ncbi.nlm.nih.gov/pubmed/27321367", "http://www.ncbi.nlm.nih.gov/pubmed/27935078", "http://www.ncbi.nlm.nih.gov/pubmed/22892472", "http://www.ncbi.nlm.nih.gov/pubmed/26871829", "http://www.ncbi.nlm.nih.gov/pubmed/27068711", "http://www.ncbi.nlm.nih.gov/pubmed/28220742", "http://www.ncbi.nlm.nih.gov/pubmed/24096524", "http://www.ncbi.nlm.nih.gov/pubmed/19317304", "http://www.ncbi.nlm.nih.gov/pubmed/25847841", "http://www.ncbi.nlm.nih.gov/pubmed/12434450", "http://www.ncbi.nlm.nih.gov/pubmed/16368166", "http://www.ncbi.nlm.nih.gov/pubmed/11012592", "http://www.ncbi.nlm.nih.gov/pubmed/16108246", "http://www.ncbi.nlm.nih.gov/pubmed/23430392", "http://www.ncbi.nlm.nih.gov/pubmed/10764004", "http://www.ncbi.nlm.nih.gov/pubmed/11273880" ], "ideal_answer": [ "Calcific uraemic arteriolopathy also known as calciphylaxis is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis.", "Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D002115", "http://www.disease-ontology.org/api/metadata/DOID:4734" ], "type": "summary", "id": "5a96f40cfcd1d6a10c00002b", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 178, "text": "Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28220742", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 357, "text": "Renal failure-associated calciphylaxis, also termed calcific uremic arteriolopathy (CUA), is a life-threatening condition usually observed in patients with end-stage renal disease on chronic dialysis or after renal transplantation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27935078", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 247, "text": "Calcific uraemic arteriolopathy (CUA, calciphylaxis) is a rare disease predominantly in dialysis patients and associated with high mortality. Painful skin ulcerations and calcification of cutaneous arterioles characterize calciphylaxis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26908770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "WHAT IS KNOWN AND OBJECTIVE: Calciphylaxis is a rare and potentially life-threatening cause of skin necrosis and is poorly recognized by clinicians in non-uraemic patients.
CASE DESCRIPTION: We report five cases of warfarin-induced calciphylaxis in patients with normal renal function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27321367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "BACKGROUND AND OBJECTIVES: Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18417747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "WHAT IS KNOWN AND OBJECTIVE Calciphylaxis is a rare and potentially life-threatening cause of skin necrosis and is poorly recognized by clinicians in non-uraemic patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27321367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "OBJECTIVE Calciphylaxis, a rare disorder typically affecting renal failure patients, results in vascular calcification with subsequent skin necrosis, gangrene, and often death from sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10764004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Calciphylaxis is a metastatic calcification-induced vasculopathy that results in the occlusion of small blood vessels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23663061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Calciphylaxis is a small vessel vasculopathy, characterized by medial wall calcification that develops in a few patients with chronic renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26871829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "BACKGROUND Calciphylaxis is a syndrome consisting of vascular calcification, thrombosis, and skin necrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27068711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Calciphylaxis is characterized by calcification in the medium and small vessel arterioles and can be a life-threatening complication often associated with chronic kidney disease (CKD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26779700", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 221, "text": "Calciphylaxis is characterized by painful, violaceous, mottled skin lesions (livedo reticularis) that may progress to tissue necrosis, nonhealing ulcers, gangrene, and potentially amputation, sepsis, or death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9426423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Calciphylaxis is a relatively rare disease, observed mainly in patients on dialysis, associated with high mortality rates, and characterized by painful skin ulceration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23430392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Calciphylaxis is a rare condition of induced systemic hypersensitivity in which tissues respond to appropriate challenging agents with a sudden local calcification. It is characterized by acute calcium deposition in the medial layer of small and intermediate dermal vasculature that can lead to epidermal ischemia, ulceration, and necrosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16108246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Calciphylaxis is a rare condition characterized by medial calcification of small- and medium-sized vessels that subsequently leads to ischemic necrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Calciphylaxis is a disease in which metastatic calcification affects small- and medium-sized vessels resulting in significant dermatologic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21410615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "Calciphylaxis is a severe complication of chronic renal failure, confined almost exclusively to patients on dialysis therapy. Histological characteristics of calciphylaxis include small-vessel calcifications of skin, subcutaneous tissue, and visceral organs. These vascular changes promote tissue ischemia that often results in tissue necrosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11273880", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 191, "text": "Calcific uraemic arteriolopathy, also named calciphylaxis, is a rare but serious disorder characterized by medial mural calcification of small vessel leading to tissue ischaemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18045036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Calciphylaxis is a rare complication that occurs in 1% of patients with end-stage renal disease (ESRD) each year. Extensive microvascular calcification and occlusion/thrombosis lead to violaceous skin lesions, which progress to nonhealing ulcers with secondary infection, often leading to sepsis and death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19317304", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 157, "text": "Calciphylaxis is a rare, usually fatal vasculopathic disorder characterized by cutaneous ischemia and necrosis due to calcification of arterioles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Calciphylaxis is a rare and potentially fatal complication of end stage renal disease (ESRD) and secondary hyperparathyroidism associated with abnormal calcium metabolism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12434450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Calciphylaxis causes calcification, thrombosis, cutaneous ischemia, and necrosis in the skin and subcutaneous tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096524", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 143, "text": "Calciphylaxis is a rare phenomenon of medium- and small-vessel calcifications leading to cutaneous necrosis mimicking vasculitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16368166", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 109, "text": " Calciphylaxis combines features of vascular thrombotic occlusion and endoluminal calcification. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25847841", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 307, "text": "Calciphylaxis refers to a syndrome of calcium deposition in the small and intermediate dermal vasculature which can lead to epidermal ischaemia, ulceration and necrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11012592", "endSection": "abstract" } ] }, { "body": "What is the alternative lengthening of telomeres?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28082393" ], "ideal_answer": [ "Alternative lengthening of telomeres (ALT) is a telomerase independent telomere maintenance mechanism that occurs in \u223c15% of cancers. It is proposed to occur preferentially at telomeric lagging strands leading to heterogeneous telomere lengths observed in most ALT cancers." ], "type": "summary", "id": "5ab908d4fcf456587200001a", "snippets": [ { "offsetInBeginSection": 495, "offsetInEndSection": 1046, "text": "By comparing these ALT cells with parental telomerase positive cells, we observed that ALT cells possess excessively long telomeric overhangs derived from telomere elongation processes that mostly occur during S phase. ALT cells exhibited preferential elongation of the telomeric lagging strands, whereas telomerase positive cells exhibited similar elongation between leading and lagging strands. We propose that the ALT pathway preferentially occurs at telomeric lagging strands leading to heterogeneous telomere lengths observed in most ALT cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28082393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Alternative lengthening of telomeres (ALT) is a telomerase independent telomere maintenance mechanism that occurs in \u223c15% of cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28082393", "endSection": "abstract" } ] }, { "body": "Which organ express and secretes the hormone FGF21?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28336912", "http://www.ncbi.nlm.nih.gov/pubmed/26872145" ], "ideal_answer": [ "Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue." ], "type": "summary", "id": "5ad3aa47133db5eb78000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in the thymus as well as in the liver. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28336912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26872145", "endSection": "abstract" } ] }, { "body": "What is the biological role of Neddylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25742093", "http://www.ncbi.nlm.nih.gov/pubmed/26437438", "http://www.ncbi.nlm.nih.gov/pubmed/25655932", "http://www.ncbi.nlm.nih.gov/pubmed/23863900", "http://www.ncbi.nlm.nih.gov/pubmed/29074978", "http://www.ncbi.nlm.nih.gov/pubmed/18793140", "http://www.ncbi.nlm.nih.gov/pubmed/27591266", "http://www.ncbi.nlm.nih.gov/pubmed/26260793", "http://www.ncbi.nlm.nih.gov/pubmed/26096160", "http://www.ncbi.nlm.nih.gov/pubmed/25628956", "http://www.ncbi.nlm.nih.gov/pubmed/25918018", "http://www.ncbi.nlm.nih.gov/pubmed/25349211", "http://www.ncbi.nlm.nih.gov/pubmed/23148618" ], "ideal_answer": [ "NEDDylation is a post-translational protein modification that is tightly linked to ubiquitination and thereby protein degradation. It however has its own enzyme machinery. It is coupled to ubiquitination and is important for maintaining cellular homeostasis.", "Neddylation is a post-translational protein modification that is tightly linked to ubiquitination and thereby protein degradation.Proteins in the neddylation pathway have also been linked to regulating ddr.Blocking neddylation could be a novel strategy for mitigating immune-mediated disease processes.", "Neddylation is a process that is similar to ubiquitination. Proteins in the neddylation pathway have also been linked to regulating DDR. Neddylation plays an important role in the regulation of murine and human dendritic cell function. NEDDylation is a post-translational protein modification that is tightly linked to ubiquitination and thereby protein degradation. Utilizing multiple but complementary approaches, we determined the role of an important but less understood type of PTM, namely, neddylation, in regulating DC functions. It is coupled to ubiquitination and is important for maintaining cellular homeostasis. " ], "type": "summary", "id": "5ace3e3f0340b9f058000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Neddylation plays an important role in the regulation of murine and human dendritic cell function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863900", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 447, "text": "Utilizing multiple but complementary approaches, we determined the role of an important but less understood type of PTM, namely, neddylation, in regulating DC functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863900", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 654, "text": "nhibition of neddylation suppressed the release of proinflammatory cytokines by DCs in response to Toll-like receptor, nucleotide oligomerization domain-like receptor, and noninfectious CD40L stimulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863900", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1448, "text": "blocking neddylation could be a novel strategy for mitigating immune-mediated disease processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23863900", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 599, "text": "Neddylation is a process that is similar to ubiquitination. It however has its own enzyme machinery. It is coupled to ubiquitination and is important for maintaining cellular homeostasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26096160", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 501, "text": "Proteins in the neddylation pathway have also been linked to regulating DDR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26437438", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 585, "text": "NEDDylation is a post-translational protein modification that is tightly linked to ubiquitination and thereby protein degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25655932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The neddylation conjugation pathway has a pivotal role in mediating ubiquitination of proteins and regulation of numerous biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23148618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The present review describes the biological significance of NEDDylation for the novel identified substrates and the emerging evidence for the co-operation between the ubiquitin and NEDD8 pathways to control protein function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18793140", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 678, "text": "By altering the substrate's conformation, stability, subcellular localization or binding affinity to DNA or proteins, neddylation regulates diverse cellular processes including the ubiquitin-proteasome system-mediated protein degradation, protein transcription, cell signaling etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628956", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 305, "text": "Similar to ubiquitination, neddylation is mediated by a cascade of three NEDD8 specific enzymes, an E1 activating enzyme, an E2 conjugating enzyme and one of the several E3 ligases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Neddylation is a post-translational protein modification that conjugates a ubiquitin-like protein NEDD8 to target proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628956", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 312, "text": "Neddylation is commonly mediated by NEDD8-specific enzymes (typical neddylation) and, sometimes, by ubiquitin enzymes (atypical neddylation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26260793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The activity of cullin-RING type ubiquitination E3 ligases is regulated by neddylation, a process analogous to ubiquitination that culminates in covalent attachment of the ubiquitin-like protein Nedd8 to cullins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25349211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The Cullin-RING E3 ubiquitin ligases (CRLs) regulate homeostasis of ~20% of cellular proteins and their activation require neddylation of their cullin subunit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29074978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Protein neddylation, a newly characterized posttranslational modification that adds the ubiquitin-like molecule NEDD8 to substrates, modulates important biological processes, whereas dysfunction of neddylation may cause several serious diseases, such as cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25742093", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 492, "text": "However, it is unknown whether and how UBE2F, a less characterized neddylation E2, regulates lung cancer cell survival, and whether and how NOXA, a proapoptotic protein, is ubiquitylated and degraded by which E3 and via which ubiquitin linkage.Experimental Design: Methods of immunohistochemistry and immunoblotting were utilized to examine UBE2F protein expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27591266", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 237, "text": "Dysregulation in the ubiquitination and neddylation pathways is associated with many cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23148618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Neddylation is a posttranslational modification that controls diverse biological processes by covalently conjugating the ubiquitin-like protein NEDD8 to specific targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26260793", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 415, "text": "Ubiquitin can form diverse polyubiquitin chains, on its seven lysines, which play important functions in various biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25918018", "endSection": "abstract" } ] }, { "body": "What is break induced replication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28427283" ], "ideal_answer": [ "Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases." ], "type": "summary", "id": "5ab9050bfcf4565872000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1245, "text": "Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA. This unusual mode of DNA replication is responsible for frequent genetic instabilities associated with BIR, including hyper-mutagenesis, which can lead to the formation of mutation clusters, extensive loss of heterozygosity, chromosomal translocations, copy-number variations and complex genomic rearrangements. In addition to budding yeast experimental systems that were initially employed to investigate eukaryotic BIR, recent studies in different organisms including humans, have provided multiple examples of BIR initiated within different cellular contexts, including collapsed replication fork and telomere maintenance in the absence of telomerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28427283", "endSection": "abstract" } ] }, { "body": "What is a fibrocyte?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27435108", "http://www.ncbi.nlm.nih.gov/pubmed/28658176", "http://www.ncbi.nlm.nih.gov/pubmed/28386106", "http://www.ncbi.nlm.nih.gov/pubmed/27709630", "http://www.ncbi.nlm.nih.gov/pubmed/28211211", "http://www.ncbi.nlm.nih.gov/pubmed/28915889", "http://www.ncbi.nlm.nih.gov/pubmed/27388852" ], "ideal_answer": [ "Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. Fibrocytes are circulating mesenchymal precursors (CD45+, col 1+) recruited to fibrotic areas." ], "type": "summary", "id": "5ad247720340b9f058000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Fibrocytes are circulating mesenchymal precursors (CD45+, col 1+) recruited to fibrotic areas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27435108", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 324, "text": "We evaluated whether bone (BM)-derived progenitor cells, fibrocytes,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27388852", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 372, "text": "Utilizing flow cytometry to identify circulating, collagen type 1+cells, we found two populations: (i) CD45+CD34+(fibrocytes)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709630", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 324, "text": " fibrocytes, the spindle-shaped fibroblast-like hematopoietic cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28386106", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 469, "text": "Circulating fibrocytes are unique haematopoietic-derived stem cells that have been reported to play a pivotal role in wound healing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28211211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Fibrocytes, ahematopoietic stem cell source of fibroblasts/myofibroblasts, were previously implicated to infiltrate into the intestinal and enhance inflammation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28658176", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 409, "text": "Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28915889", "endSection": "abstract" } ] }, { "body": "Which cellular functions are affected by lncRNA H19 in the heart?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27789555", "http://www.ncbi.nlm.nih.gov/pubmed/28430627", "http://www.ncbi.nlm.nih.gov/pubmed/27318893", "http://www.ncbi.nlm.nih.gov/pubmed/27903964", "http://www.ncbi.nlm.nih.gov/pubmed/27895893" ], "ideal_answer": [ "H19 could inhibit autophagy in cardiomyocytes by epigenetically silencing of DIRAS3. Elevated H19 promotes apoptosis through PA2G4. Downregulation of H19 promotes proliferation and inhibits apoptosis. H19 induces mineralization of valve interstitial cells. H19 contributes to cardiac fibroblast proliferation and fibrosis, which act in part through repression of DUSP5/ERK1/2." ], "exact_answer": [ [ "inhibits autophagy" ], [ "promotes apoptosis" ], [ "inhibits proliferation" ], [ "induced mineralization of valve interstitial cells" ], [ "promotes cardiac fibroblast proliferation" ], [ "promotes fibrosis" ] ], "type": "list", "id": "5ac7185f0340b9f058000004", "snippets": [ { "offsetInBeginSection": 740, "offsetInEndSection": 925, "text": "In addition, overexpression of H19 was found to downregulate DIRAS3 expression, promote mTOR phosphorylation and inhibit autophagy activation in cardiomyocytes exposed to high glucose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27903964", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1306, "text": "In conclusion, our study suggested that H19 could inhibit autophagy in cardiomyocytes by epigenetically silencing of DIRAS3, which might provide novel insights into understanding the molecular mechanisms of diabetic cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27903964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27903964", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The long non-coding RNA H19 promotes cardiomyocyte apoptosis in dilated cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430627", "endSection": "title" }, { "offsetInBeginSection": 314, "offsetInEndSection": 575, "text": "H19 knockdown in the myocardium of DCM rats attenuated cardiomyocyte apoptosis and improved left ventricular structure and function. Adriamycin treatment was associated with elevated H19 and miR-675 expression and increased apoptosis in neonatal cardiomyocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430627", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1374, "text": "Moreover, H19 knockdown was found to increase PA2G4 expression and suppress apoptosis in cardiomyocytes exposed to adriamycin. In conclusion, our study suggests that H19/miR-675 axis is involved in the promotion of cardiomyocyte apoptosis by targeting PA2G4, which may provide a new therapeutic strategy for the treatment of adriamycin-induced DCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Downregulation of long non-coding RNA H19 promotes P19CL6 cells proliferation and inhibits apoptosis during late-stage cardiac differentiation via miR-19b-modulated Sox6.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895893", "endSection": "title" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1230, "text": "Biological function analysis showed that knockdown of H19 promoted cell proliferation and inhibits cell apoptosis. H19 suppressed miR-19b expression and miR-19b targeted Sox6, which inhibited cell proliferation and promoted apoptosis in P19CL6 cells during late-stage cardiac differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895893", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1638, "text": "Downregulation of H19 promoted cell proliferation and inhibited cell apoptosis during late-stage cardiac differentiation by regulating the negative role of miR-19b in Sox6 expression, which suggested that the manipulation of H19 expression could serve as a potential strategy for heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895893", "endSection": "abstract" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1009, "text": "Knockdown and overexpression experiments showed that H19 induces a strong osteogenic phenotype by altering the NOTCH1 pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789555", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1460, "text": "A knockdown of H19 in valve interstitial cells (VICs) increased the expression of NOTCH1 and decreased the level of RUNX2 and BMP2, 2 downstream targets repressed by NOTCH1. In rescue experiments, the transfection of a vector encoding for the active Notch intracellular domain prevented H19-induced mineralization of valve interstitial cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Long noncoding RNA H19 controls DUSP5/ERK1/2 axis in cardiac fibroblast proliferation and fibrosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27318893", "endSection": "title" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1580, "text": "H19 ectopic overexpression reduces DUSP5 abundance and increases the proliferation of cardiac fibroblast, whereas H19 silencing causes the opposite effects. In a broader perspective, these results demonstrated that LncRNA H19 contributes to cardiac fibroblast proliferation and fibrosis, which act in part through repression of DUSP5/ERK1/2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27318893", "endSection": "abstract" } ] }, { "body": "Dinutuximab is used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26934530", "http://www.ncbi.nlm.nih.gov/pubmed/26917818", "http://www.ncbi.nlm.nih.gov/pubmed/27756784", "http://www.ncbi.nlm.nih.gov/pubmed/26791869", "http://www.ncbi.nlm.nih.gov/pubmed/28748630", "http://www.ncbi.nlm.nih.gov/pubmed/28061552", "http://www.ncbi.nlm.nih.gov/pubmed/25940913", "http://www.ncbi.nlm.nih.gov/pubmed/26891967", "http://www.ncbi.nlm.nih.gov/pubmed/28389455" ], "ideal_answer": [ "Dinutuximab, a monoclonal antibody against disialoganglioside, is used for treatment of high-risk neuroblastoma." ], "exact_answer": [ "neuroblastoma" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D013812", "https://meshb.nlm.nih.gov/record/ui?ui=D004194" ], "type": "factoid", "id": "589a247078275d0c4a000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "PURPOSE: Dinutuximab (Unituxin\u2122; ch14.18), a monoclonal antibody against disialoganglioside, improved survival as part of post-consolidation therapy for high-risk neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26791869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Dinutuximab: A Review in High-Risk Neuroblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26891967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "Dinutuximab (ch14.18; Unituxin\u2122) is a chimeric human-mouse monoclonal antibody that binds to the glycolipid antigen disialoganglioside, which is highly expressed on the surface of neuroblastoma cells. This intravenous drug is approved in the EU and USA as combination therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-2 and isotretinoin for the postconsolidation treatment of patients with high-risk neuroblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26891967", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1592, "text": "Dinutuximab administered in combination with GM-CSF, IL-2 and isotretinoin represents an important advance in the postconsolidation treatment of patients with high-risk neuroblastoma, with its benefits outweighing its risks in a patient population with a poor prognosis and limited therapeutic options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26891967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26934530", "endSection": "title" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1128, "text": "The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26934530", "endSection": "abstract" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1921, "text": "Severe adverse effects of dinutuximab include pain, hypersensitivity reactions, capillary leak syndrome, and hypotension.
CONCLUSIONS: Dinutuximab is the first anti-GD2 monoclonal antibody approved in combination with GM-CSF, IL-2, and RA for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917818", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1378, "text": "Dinutuximab is a chimeric, human-murine, anti-GD2 monoclonal antibody approved in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917818", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1021, "text": "The recommended dosage of dinutuximab is 17.5 mg/m
CONCLUSION: Dinutuximab is a novel monoclonal antibody that is efficacious as part of combination immunotherapy in pediatric patients with high-risk neuroblastoma.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Immunotherapy with the anti-GD2 monoclonal antibody ch14.18, or dinutuximab, represents an important therapeutic advance in the treatment of pediatric high-risk neuroblastoma and is now considered part of standard of care in this patient population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 484, "text": "PURPOSE: The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of dinutuximab for the treatment of high-risk pediatric neuroblastoma are reviewed.
SUMMARY: Dinutuximab (Unituxin, United Therapeutics) is a novel monoclonal antibody recently approved for use in combination with granulocyte- macrophage colony-stimulating factor, interleukin-2, and isotretinoin for the treatment of pediatric patients with high-risk neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389455", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1186, "text": "This article summarizes the milestones in the development of dinutuximab leading to this first approval for use (in combination with granulocyte macrophage colony-stimulating factor, interleukin-2 and 13-cis retinoic acid) in the treatment of paediatric patients with high-risk neuroblastoma who achieve at least partial response to prior first-line multiagent, multimodality therapy.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25940913", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 635, "text": "The US FDA has recently approved the use of dinutuximab combination therapy for the treatment of high-risk neuroblastoma in paediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25940913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "United Therapeutics Corporation and the National Cancer Institute are developing dinutuximab (Unituxin\u2122; ch14.18), a monoclonal antibody targeting GD2, for the treatment of neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25940913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "TGF\u03b2R1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756784", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "PURPOSE: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27756784", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1343, "text": "Dinutuximab is a chimeric, human-murine, anti-GD2 monoclonal antibody approved in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917818", "endSection": "abstract" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1877, "text": "CONCLUSIONS Dinutuximab is the first anti-GD2 monoclonal antibody approved in combination with GM-CSF, IL-2, and RA for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "United Therapeutics Corporation and the National Cancer Institute are developing dinutuximab (Unituxin\u2122; ch14.18), a monoclonal antibody targeting GD2, for the treatment of neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25940913", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 467, "text": "SUMMARY Dinutuximab (Unituxin, United Therapeutics) is a novel monoclonal antibody recently approved for use in combination with granulocyte- macrophage colony-stimulating factor, interleukin-2, and isotretinoin for the treatment of pediatric patients with high-risk neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389455", "endSection": "abstract" }, { "offsetInBeginSection": 1499, "offsetInEndSection": 1661, "text": "CONCLUSION Dinutuximab is a novel monoclonal antibody that is efficacious as part of combination immunotherapy in pediatric patients with high-risk neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389455", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 323, "text": "Dinutuximab (formerly called ch14.18), a monoclonal antibody targeting the disialoganglioside GD2, has been shown to significantly improve survival rates in patients with high-risk neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28061552", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Dinutuximab (ch14.18; Unituxin\u2122) is a chimeric human-mouse monoclonal antibody that binds to the glycolipid antigen disialoganglioside, which is highly expressed on the surface of neuroblastoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26891967", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 637, "text": "The US FDA has recently approved the use of dinutuximab combination therapy for the treatment of high-risk neuroblastoma in paediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25940913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26934530", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Transverse myelitis as an unexpected complication following treatment with dinutuximab in pediatric patients with high-risk neuroblastoma: A case series.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748630", "endSection": "title" }, { "offsetInBeginSection": 539, "offsetInEndSection": 687, "text": "Findings of the randomized phase III study (ANBL0032) led to the approval of dinutuximab for the treatment of children with high-risk neuroblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28061552", "endSection": "abstract" } ] }, { "body": "What is the ChIP-exo method used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23026909", "http://www.ncbi.nlm.nih.gov/pubmed/28060339", "http://www.ncbi.nlm.nih.gov/pubmed/26404150" ], "ideal_answer": [ "Precise Identification of DNA-Binding Proteins Genomic Location by Exonuclease Coupled Chromatin Immunoprecipitation (ChIP-exo).", "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. ", "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. ChIP-exo allows identification of a nearly complete set of the binding locations of DNA-binding proteins at near-single-nucleotide resolution with almost no background. Precise Identification of DNA-Binding Proteins Genomic Location by Exonuclease Coupled Chromatin Immunoprecipitation (ChIP-exo).", "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy.", "ChIP-exo is a molecular biology method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy.", "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. ChIP-exo allows identification of a nearly complete set of the binding locations of DNA-binding proteins at near-single-nucleotide resolution with almost no background.", "ChIP-exo allows identification of a nearly complete set of the binding locations of DNA-binding proteins at near-single-nucleotide resolution with almost no background. The key distinction of the ChIP-exo methodology is the incorporation of lambda exonuclease digestion in the library preparation workflow to effectively footprint the left and right 5' DNA borders of the protein-DNA crosslink site. " ], "exact_answer": [ "location of DNA binding proteins at high resolution" ], "type": "factoid", "id": "5ac24c9495d0062724000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026909", "endSection": "title" }, { "offsetInBeginSection": 172, "offsetInEndSection": 340, "text": "ChIP-exo allows identification of a nearly complete set of the binding locations of DNA-binding proteins at near-single-nucleotide resolution with almost no background.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Precise Identification of DNA-Binding Proteins Genomic Location by Exonuclease Coupled Chromatin Immunoprecipitation (ChIP-exo).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404150", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 870, "text": "A significant improvement of the ChIP-seq technique results from the addition of an exonuclease treatment during the immunoprecipitation step (ChIP-exo) that lowers background noise and more importantly increases the identification of binding sites to a level near to single-base resolution by effectively footprinting DNA-bound proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The ChIP-exo Method: Identifying Protein-DNA Interactions with Near Base Pair Precision.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28060339", "endSection": "title" }, { "offsetInBeginSection": 545, "offsetInEndSection": 776, "text": "The key distinction of the ChIP-exo methodology is the incorporation of lambda exonuclease digestion in the library preparation workflow to effectively footprint the left and right 5' DNA borders of the protein-DNA crosslink site. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28060339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23026909", "endSection": "title" } ] }, { "body": "Where do mitochondrial DNA deletion breakpoints tend to occur?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25193669", "http://www.ncbi.nlm.nih.gov/pubmed/10912916", "http://www.ncbi.nlm.nih.gov/pubmed/26530670", "http://www.ncbi.nlm.nih.gov/pubmed/22661583", "http://www.ncbi.nlm.nih.gov/pubmed/9128755", "http://www.ncbi.nlm.nih.gov/pubmed/25124333" ], "ideal_answer": [ "Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures.", "Non-B DNA conformations are a key element of the mtDNA deletion process and most of the analyzed deletion breakpoints showed nucleotide repeats flanking the deletions. Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. Current findings suggest that mitochondrial G-quadruplexes are also likely to be a source of instability for the mitochondrial genome by perturbing the normal progression of the mitochondrial replication machinery, including DNA unwinding by Twinkle helicase.", "n this work, we performed a computational analysis of the human mitochondrial genome using the \"Pattern Finder\" G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints.", "Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys. Most of the analyzed deletion breakpoints showed nucleotide repeats flanking the deletions. N this work, we performed a computational analysis of the human mitochondrial genome using the \"Pattern Finder\" G-quadruplex to known mitochondrial DNA deletion breakpoints. " ], "exact_answer": [ "Near mitochondrial G-rich sequences " ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D054856" ], "type": "factoid", "id": "5abc9ecffcf4565872000021", "snippets": [ { "offsetInBeginSection": 349, "offsetInEndSection": 635, "text": "n this work, we performed a computational analysis of the human mitochondrial genome using the \"Pattern Finder\" G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25193669", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 1002, "text": "Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25193669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9128755", "endSection": "title" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1350, "text": "Most of the analyzed deletion breakpoints showed nucleotide repeats flanking the deletions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10912916", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 841, "text": "Currently, the multiple types of GQ sequences and their association with human mtDNA stability are unknown.
RESULTS: Here, we show an association between human mtDNA deletion breakpoint locations (sites where DNA ends rejoin after deletion of a section) and sequences with G-quadruplex forming potential (QFP), and establish the ability of selected sequences to form GQ in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25124333", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1403, "text": "A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25193669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25193669", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25124333", "endSection": "title" } ] }, { "body": "Name 4 circular RNA molecules associated with carcinogenesis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28639908", "http://www.ncbi.nlm.nih.gov/pubmed/28253710", "http://www.ncbi.nlm.nih.gov/pubmed/28744405", "http://www.ncbi.nlm.nih.gov/pubmed/28903484" ], "ideal_answer": [ "circ-ABCB10 knockdown suppressed the proliferation and increased apoptosis of breast cancer cells.\nHsa_circ_0058246 was elevated in tumor specimens of patients with poor clinical outcomes.\nCirc-FBXW7 expression positively associated with glioblastoma patient overall survival.\nciRS-7 promotes the development of cancer by acting as sponge of miR-7." ], "exact_answer": [ [ "ciRS-7" ], [ "FBXW7" ], [ "circ-ABCB10" ], [ "hsa_circ_0058246" ] ], "type": "list", "id": "5ac721230340b9f058000005", "snippets": [ { "offsetInBeginSection": 441, "offsetInEndSection": 578, "text": " In particular, we found that the expression of hsa_circ_0058246 was elevated in tumor specimens of patients with poor clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28639908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression through sponging miR-1271.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28744405", "endSection": "title" }, { "offsetInBeginSection": 405, "offsetInEndSection": 487, "text": "Results found circ-ABCB10, was significantly up-regulated in breast cancer tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28744405", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 685, "text": "In vitro, loss-of-function experiments showed circ-ABCB10 knockdown suppressed the proliferation and increased apoptosis of breast cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28744405", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1203, "text": "Overall, results identified a new functional circ-ABCB10 in breast cancer tumorigenesis, and reveal the important regulatory role of circ-ABCB10 through sponging miR-1271, providing a novel insight for breast cancer pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28744405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "endSection": "title" }, { "offsetInBeginSection": 1371, "offsetInEndSection": 1549, "text": "Upregulation of FBXW7-185aa in cancer cells inhibited proliferation and cell cycle acceleration, while knockdown of FBXW7-185aa promoted malignant phenotypes invitro and invivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "endSection": "abstract" }, { "offsetInBeginSection": 1643, "offsetInEndSection": 2053, "text": "Moreover, circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma clinical samples compared with their paired tumor-adjacent tissues (P<.001). Circ-FBXW7 expression positively associated with glioblastoma patient overall survival (P = .03).Conclusions: Endogenous circRNA encodes a functional protein in human cells, and circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28903484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Detection and characterization of ciRS-7: a potential promoter of the development of cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253710", "endSection": "title" }, { "offsetInBeginSection": 697, "offsetInEndSection": 975, "text": "Most recently, a study reported ciRS-7 acted as an oncogene in hepatocellular carcinoma through targeting miR-7 expression. This suggest ciRS-7/ miR-7 axis affects oncogenesis, and it provides a new perspective on the mechanisms of decreased miR-7 expression in cancer tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253710", "endSection": "abstract" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1400, "text": "This review summarizes the structure and function of circRNAs and provides evidence for the impact of ciRS-7 in promoting the development of cancer by acting as sponge of miR-7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253710", "endSection": "abstract" } ] }, { "body": "Which is the enzymatic activity of nardilysin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27385158", "http://www.ncbi.nlm.nih.gov/pubmed/28230087" ], "ideal_answer": [ "Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins." ], "exact_answer": [ "Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins." ], "type": "factoid", "id": "5ac138aa95d0062724000001", "snippets": [ { "offsetInBeginSection": 315, "offsetInEndSection": 597, "text": "Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28230087", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 333, "text": " nardilysin (N-arginine dibasic convertase;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27385158", "endSection": "abstract" } ] }, { "body": "The Mantoux test detects what latent infection/disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28337457", "http://www.ncbi.nlm.nih.gov/pubmed/12238571", "http://www.ncbi.nlm.nih.gov/pubmed/27187878", "http://www.ncbi.nlm.nih.gov/pubmed/16307510", "http://www.ncbi.nlm.nih.gov/pubmed/27529924", "http://www.ncbi.nlm.nih.gov/pubmed/17663901", "http://www.ncbi.nlm.nih.gov/pubmed/11089393", "http://www.ncbi.nlm.nih.gov/pubmed/28276801", "http://www.ncbi.nlm.nih.gov/pubmed/25401733", "http://www.ncbi.nlm.nih.gov/pubmed/21822042" ], "ideal_answer": [ "screened for TB infection with a Mantoux tuberculin skin testtuberculin skin test (TST) performed according to the Mantoux method.", "screened for TB infection with a Mantoux tuberculin skin test ", "The Mantoux tuberculin skin test tests for latent tuberculosis", "screened for TB infection with a Mantoux tuberculin skin test. " ], "exact_answer": [ "tuberculosis" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D055985", "https://meshb.nlm.nih.gov/record/ui?ui=D012882", "https://meshb.nlm.nih.gov/record/ui?ui=D014374" ], "type": "factoid", "id": "5ab147edfcf4565872000013", "snippets": [ { "offsetInBeginSection": 659, "offsetInEndSection": 721, "text": "screened for TB infection with a Mantoux tuberculin skin test ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28276801", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 606, "text": "The present study reports the results of a three-year TB surveillance among HCW in a large teaching hospital in Rome, using TST (by standard Mantoux technique)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28337457", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1594, "text": "Laboratory diagnostic testing of cellular immunity against pathogenic mycobacteria employs the tuberculin skin test (TST, Mantoux tuberculin test) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27187878", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 491, "text": "tuberculin skin test (TST) performed according to the Mantoux method. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25401733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Diaskintest\u00ae test and Mantoux test with 2TE PPD-L were concurrently carried out in 300 children and adolescents with tuberculosis and followed up in risk groups at a tuberculosis dispensary to determine the sensitivity of the new skin test in active tuberculosis infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27529924", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1624, "text": "Latent tuberculosis treatment was recommended in all Mantoux-positive contacts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17663901", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 440, "text": "The prevalence of tuberculosis infection among hospitalized patients in a pneumological department of an inner-city hospital was evaluated, using the intradermal tuberculin skin test (Mantoux technique). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11089393", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 657, "text": "he 100-year-old tuberculin skin test (Mantoux) has been the only available diagnostic test for latent tuberculosis infection, despite its many well-known limitations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16307510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "In order to determine the prevalence of latent infection due to Mycobacterium tuberculosis in drug users and to provide centres for drug users with a practical tool for tuberculosis screening, 237 drug users were subjected to the Monotest and, for reference purposes, to the Mantoux test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12238571", "endSection": "abstract" } ] }, { "body": "What is measured with the Proseek panels?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28734077", "http://www.ncbi.nlm.nih.gov/pubmed/28930774", "http://www.ncbi.nlm.nih.gov/pubmed/26475405", "http://www.ncbi.nlm.nih.gov/pubmed/27383427", "http://www.ncbi.nlm.nih.gov/pubmed/29026368", "http://www.ncbi.nlm.nih.gov/pubmed/28083617", "http://www.ncbi.nlm.nih.gov/pubmed/29050213", "http://www.ncbi.nlm.nih.gov/pubmed/28948068", "http://www.ncbi.nlm.nih.gov/pubmed/28586402", "http://www.ncbi.nlm.nih.gov/pubmed/26204497", "http://www.ncbi.nlm.nih.gov/pubmed/29051715", "http://www.ncbi.nlm.nih.gov/pubmed/28437237" ], "ideal_answer": [ "Differnet Proseek multiplex protein biomarker panels exists: CVD, inflammatory, neurology and oncology biomarker." ], "exact_answer": [ "Differnet Proseek multiplex protein biomarker panels exists: CVD, inflammatory, neurology and oncology biomarker." ], "type": "factoid", "id": "5a9d99ac4e03427e73000002", "snippets": [ { "offsetInBeginSection": 215, "offsetInEndSection": 360, "text": "A total of 92 biomarkers were measured before a standardized meal as well as 30 and 120 minutes afterwards with the Proseek Multiplex CVD III kit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28586402", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 926, "text": " PROSEEK Multiplex CVD and PROSEEK Multiplex INF ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28437237", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 455, "text": "A multiplex proximity extension assay allowed us to measure 157 cardiovascular disease (CVD) and inflammatory disease-related biomarkers in patients from the international, multicenter, and randomized trial;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28437237", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 702, "text": "Plasma concentrations of MMP12 were measured at baseline in 3394 subjects with high-risk for cardiovascular disease (CVD) using the Olink ProSeek CVD I array. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28734077", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 948, "text": "The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek Multiplex Inflammation I; Olink Bioscience, Uppsala, Sweden).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28930774", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 448, "text": " A total of 92 biomarkers were measured before a standardized meal as well as 30 and 120\u00a0min afterward with the Proseek Multiplex Neurology\u00a0I kit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28948068", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 651, "text": "We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n\u00a0=\u00a075) and age-matched healthy control subjects (n\u00a0=\u00a023)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29026368", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 266, "text": "Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29050213", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 530, "text": "This new technology (Proseek\u00aeMultiplex Oncology Plates) can simultaneously measure the expression of 92 proteins in serum based on a proximity extension assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29051715", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 539, "text": "Levels of 82 proteins were assessed in plasma by a proximity extension assay (Proseek Multiplex CVD,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26204497", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 927, "text": "92 inflammatory proteins were analysed with a multiplex system (Proseek Multiplex Inflammation I, Olink Bioscience)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27383427", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 829, "text": "erum concentrations of 92 inflammation-associated proteins were measured in samples obtained from 80 aHSCT patients 14\u00a0days after transplantation and from 23 healthy control subjects by a novel sensitive proximity extension assay technology using Proseek Multiplex Inflammation I kit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28083617", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1174, "text": " Laboratory analyses were performed by Proximity Extension Assay (Proseek Multiplex CVD I(96 \u00d7 96)), ELISAs and RT-PCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26475405", "endSection": "abstract" } ] }, { "body": "Is Enlimomab effective for stroke treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9744839", "http://www.ncbi.nlm.nih.gov/pubmed/9693236", "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "http://www.ncbi.nlm.nih.gov/pubmed/19849665" ], "ideal_answer": [ "No. Anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in and may significantly worsen stroke outcome." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D016896", "http://www.biosemantics.org/jochem#4002166", "https://meshb.nlm.nih.gov/record/ui?ui=D020521" ], "type": "yesno", "id": "58ec6eb5eda5a5767200000c", "snippets": [ { "offsetInBeginSection": 1441, "offsetInEndSection": 1524, "text": "However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9744839", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1498, "text": "There was no increase in the frequency of adverse events with increasing doses of enlimomab.CONCLUSIONS: Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9693236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND AND PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 1791, "offsetInEndSection": 1968, "text": "These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1359, "text": "Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1630, "text": "CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Patients experiencing fever were more likely to have a poor outcome or die.The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1271, "text": "The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1674, "text": "Patients experiencing fever were more likely to have a poor outcome or die.
CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1934, "offsetInEndSection": 2068, "text": "Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19849665", "endSection": "abstract" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1635, "text": "CONCLUSIONS The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "BACKGROUND AND PURPOSE Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1591, "text": "The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" } ] }, { "body": "Are AAV vectors considered for the treatment of retinal dystrophies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26609316" ], "ideal_answer": [ "Yes, AAV vectors are considered for the treatment of retinal dystrophies." ], "exact_answer": "yes", "type": "yesno", "id": "5a74acd80384be9551000006", "snippets": [ { "offsetInBeginSection": 282, "offsetInEndSection": 529, "text": " These novel gene vectors aim to more safely and efficiently transduce retinal cells, expand the gene packaging capacity of AAV, and utilize new strategies to correct the varying mechanisms of dysfunction found with inherited retinal dystrophies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26609316", "endSection": "abstract" } ] }, { "body": "Does International Citicoline Trial on acUte Stroke trial supports efficacy of citicoline for stroke treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27072975", "http://www.ncbi.nlm.nih.gov/pubmed/22691567", "http://www.ncbi.nlm.nih.gov/pubmed/23600725" ], "ideal_answer": [ "No. The International Citicoline Trial on acUte Stroke (ICTUS) found that citocoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke." ], "exact_answer": "no", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D013812", "https://meshb.nlm.nih.gov/record/ui?ui=D020521" ], "type": "yesno", "id": "58ec709aeda5a5767200000e", "snippets": [ { "offsetInBeginSection": 794, "offsetInEndSection": 1098, "text": "The meta-analysis showed that no significant differences were found in the long-term mortality (OR=0.91, 95% CI 0.07 to 1.09, P=0.30), the rate of dependency (OR=1.02, 95% CI 0.87 to 1.24, P=0.85), and the effective rate (OR=0.98, 95% CI 0.84 to 1.14, P=0.82) between citicoline group and control group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072975", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1498, "text": " In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072975", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 368, "text": "In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23600725", "endSection": "abstract" }, { "offsetInBeginSection": 1902, "offsetInEndSection": 2054, "text": "INTERPRETATION: Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22691567", "endSection": "abstract" }, { "offsetInBeginSection": 1480, "offsetInEndSection": 1594, "text": "The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22691567", "endSection": "abstract" }, { "offsetInBeginSection": 1714, "offsetInEndSection": 1802, "text": "Global recovery was similar in both groups (odds ratio 1\u00b703, 95% CI 0\u00b786-1\u00b725; p=0\u00b7364).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22691567", "endSection": "abstract" }, { "offsetInBeginSection": 1919, "offsetInEndSection": 2070, "text": "INTERPRETATION Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22691567", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 455, "text": "In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. Several mechanisms have been proposed to explain the beneficial actions of CDP-choline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23600725", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 367, "text": "In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23600725", "endSection": "abstract" } ] }, { "body": "Is human lysyl oxidase-like 2 a glycoprotein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21954900", "http://www.ncbi.nlm.nih.gov/pubmed/23319596" ], "ideal_answer": [ "Yes, human lysyl oxidase-like 2 is a glycoprotein." ], "exact_answer": "yes", "type": "yesno", "id": "5ad240f70340b9f058000015", "snippets": [ { "offsetInBeginSection": 1382, "offsetInEndSection": 1580, "text": "This method was successfully applied to a novel recombinant protein, human lysyl oxidase-like 2. Furthermore, the glycosylation PTMs were readily detected at two glycosylation sites in the protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21954900", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 232, "text": "application to the characterization of human lysyl oxidase-like 2 glycosylation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21954900", "endSection": "title" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1531, "text": "These results suggest that the N-glycan at Asn-644 of hLOXL2 enhances the solubility and stability of the LOX catalytic domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23319596", "endSection": "abstract" } ] }, { "body": "Can GDF15 be a biomarker for metformin treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27974345" ], "ideal_answer": [ "Yes, GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin." ], "exact_answer": "yes", "type": "yesno", "id": "5ad3013d0340b9f058000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Growth Differentiation Factor 15 as a Novel Biomarker for Metformin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27974345", "endSection": "title" }, { "offsetInBeginSection": 868, "offsetInEndSection": 1003, "text": "GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27974345", "endSection": "abstract" } ] }, { "body": "Has rituximab been considered as a treatment for chronic fatigues syndrome? (November 2017)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28052319" ], "ideal_answer": [ "The use of rituximab may be of benefit for CFS/ME, but the evidence of its effectiveness is still limited." ], "exact_answer": "yes", "type": "yesno", "id": "5aa395fcd6d6b54f79000007", "snippets": [ { "offsetInBeginSection": 595, "offsetInEndSection": 794, "text": " The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28052319", "endSection": "abstract" } ] }, { "body": "Does oncogene-induced DNA replication stress inhibit genomic instability?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23204322" ], "ideal_answer": [ "No, oncogene-induced DNA replication stress is thought to drive genomic instability." ], "exact_answer": "no", "type": "yesno", "id": "5ab9032afcf4565872000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Oncogene-induced DNA replication stress is thought to drive genomic instability in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204322", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1278, "text": "We propose that single-stranded DNA generated in response to oncogene-induced replication stress compromises the repair of deaminated cytosines and other damaged bases, leading to the observed SNS mutator phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204322", "endSection": "abstract" } ] }, { "body": "Is the petrous bone used in ancient DNA sampling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28526291", "http://www.ncbi.nlm.nih.gov/pubmed/28625158", "http://www.ncbi.nlm.nih.gov/pubmed/27355351", "http://www.ncbi.nlm.nih.gov/pubmed/28129388", "http://www.ncbi.nlm.nih.gov/pubmed/26595274" ], "ideal_answer": [ "Large-scale genomic analyses of ancient human populations have become feasible partly due to refined sampling methods. The inner part of petrous bones and the cementum layer in teeth roots are currently recognized as the best substrates for such research." ], "exact_answer": "yes", "type": "yesno", "id": "5abd3707fcf456587200002d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Large-scale genomic analyses of ancient human populations have become feasible partly due to refined sampling methods. The inner part of petrous bones and the cementum layer in teeth roots are currently recognized as the best substrates for such research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28129388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 495, "text": "Ancient DNA (aDNA) research involves invasive and destructive sampling procedures that are often incompatible with anthropological, anatomical, and bioarcheological analyses requiring intact skeletal remains. The osseous labyrinth inside the petrous bone has been shown to yield higher amounts of endogenous DNA than any other skeletal element; however, accessing this labyrinth in cases of a complete or reconstructed skull involves causing major structural damage to the cranial vault or base.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28625158", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 554, "text": "first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26595274", "endSection": "abstract" } ] }, { "body": "Is recursive splicing more common in short introns?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19924226", "http://www.ncbi.nlm.nih.gov/pubmed/15802507", "http://www.ncbi.nlm.nih.gov/pubmed/25970244", "http://www.ncbi.nlm.nih.gov/pubmed/25970246", "http://www.ncbi.nlm.nih.gov/pubmed/12761221", "http://www.ncbi.nlm.nih.gov/pubmed/19683670", "http://www.ncbi.nlm.nih.gov/pubmed/27965595", "http://www.ncbi.nlm.nih.gov/pubmed/25800735" ], "ideal_answer": [ "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing.", "Together, these results indicate that recursive splicing is commonly used in Drosophila, occurs in humans, and provides insight into the mechanisms by which some large introns are removed. ", "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together Cutting a Long Intron Short: Recursive Splicing and Its Implications.", "Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing. It is more common in large/long introns.", "Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns > 20 kb , but they are found only at the expected frequency on the antisense strands , and they are underrepresented within introns < 10 kb.Using a computational analysis of the genomic sequences , we show that vertebrates lack the proper enrichment of rp-sites in their large introns , and , therefore , require some other method to aid splicing.", "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together" ], "exact_answer": "no", "type": "yesno", "id": "5abc974bfcf456587200001f", "snippets": [ { "offsetInBeginSection": 649, "offsetInEndSection": 842, "text": "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27965595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Cutting a Long Intron Short: Recursive Splicing and Its Implications.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27965595", "endSection": "title" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1391, "text": " Furthermore, we uncover the potential to investigate the multi-step nature of splicing, assessing various types of recursive splicing events", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25800735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25970244", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1226, "text": "Together, these results indicate that recursive splicing is commonly used in Drosophila, occurs in humans, and provides insight into the mechanisms by which some large introns are removed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25970244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Recursive splicing in long vertebrate genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25970246", "endSection": "title" }, { "offsetInBeginSection": 567, "offsetInEndSection": 651, "text": "Moreover, the RS-sites are found in some of the longest introns across vertebrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25970246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "The peculiarities of large intron splicing in animals.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19924226", "endSection": "title" }, { "offsetInBeginSection": 157, "offsetInEndSection": 319, "text": "These \"large introns\" must be spliced out of the pre-mRNA in a timely fashion, which involves bringing together distant 5' and 3' acceptor and donor splice sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19924226", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 782, "text": "Using a computational analysis of the genomic sequences, we show that vertebrates lack the proper enrichment of RP-sites in their large introns, and, therefore, require some other method to aid splicing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19924226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802507", "endSection": "title" }, { "offsetInBeginSection": 365, "offsetInEndSection": 644, "text": "Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns>20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns<10 kb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "These transcripts arise by use of two alternative transcription sites and complex alternative splicing mechanisms and encode proteins with long or short N-terminal domains, complete or incomplete GGL domains, 7 distinct C-terminal domains and a common internal domain where the RGS domain is found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12761221", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 970, "text": "These patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802507", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Many genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15802507", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 310, "text": "However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25970246", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1153, "text": "The effect of splice site strength was context-dependent and much more significant for the 3' splice site of the longer alternative intron than for the 3' splice site of the shorter alternative intron and the common 5' splice sites; it was also more significant in the rat minigene than in the mouse minigene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19683670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Cutting a Long Intron Short: Recursive Splicing and Its Implications.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27965595", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Recursive splicing in long vertebrate genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25970246", "endSection": "title" } ] }, { "body": "Is Lysyl oxidase crosslinking collagen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27694892", "http://www.ncbi.nlm.nih.gov/pubmed/28125844", "http://www.ncbi.nlm.nih.gov/pubmed/28041746", "http://www.ncbi.nlm.nih.gov/pubmed/28073888", "http://www.ncbi.nlm.nih.gov/pubmed/28273952" ], "ideal_answer": [ "Yes, lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions." ], "exact_answer": "yes", "type": "yesno", "id": "5ac07b67dd95b2cd42000001", "snippets": [ { "offsetInBeginSection": 136, "offsetInEndSection": 286, "text": "Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28273952", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1093, "text": "Lysyl oxidase-like 1, a crosslinking enzyme implicated in collagen and elastin biogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28125844", "endSection": "abstract" }, { "offsetInBeginSection": 1682, "offsetInEndSection": 1718, "text": "LOXL2 mediates collagen crosslinking", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28073888", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1034, "text": "The same was true for assaying lysyl oxidase, an enzyme involved in crosslinking of matrix molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28041746", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1108, "text": " In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27694892", "endSection": "abstract" } ] }, { "body": "Is sternotomy closure done using either a sternal ZipFix\u2122 implant or conventional steel wire following cardiac surgery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26290838", "http://www.ncbi.nlm.nih.gov/pubmed/22731778", "http://www.ncbi.nlm.nih.gov/pubmed/23624983", "http://www.ncbi.nlm.nih.gov/pubmed/14602299" ], "ideal_answer": [ "Yes, closure of the sternum following cardiac surgery can be done using a wire closure or sternal ZipFix\u2122 a cable-tie-based system which is fast, easy to use, reliable and safe." ], "exact_answer": "yes", "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D000072836", "https://meshb.nlm.nih.gov/record/ui?ui=D056346", "https://meshb.nlm.nih.gov/record/ui?ui=D065506", "https://meshb.nlm.nih.gov/record/ui?ui=D001864", "https://meshb.nlm.nih.gov/record/ui?ui=D013903" ], "type": "yesno", "id": "5ab2cdc5fcf4565872000016", "snippets": [ { "offsetInBeginSection": 13, "offsetInEndSection": 220, "text": "o determine the difference in sternal infection and other infectious events between conventional wire and cable-tie-based closure techniques post-sternotomy in a collective of patients after cardiac surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624983", "endSection": "abstract" }, { "offsetInBeginSection": 1678, "offsetInEndSection": 1927, "text": "Our study underlines a neutral effect of the sternal ZipFix\u2122 system in patients regarding sternal infection. Postoperative complications are similar in both sternal closure methods. The cable-tie-based system is fast, easy to use, reliable and safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624983", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 373, "text": " Wire closure still remains the preferred technique despite reasonable disadvantages. Associated complications, such as infection and sternal instability, cause time- and cost-consuming therapies. We present a new tool for sternal closure with its first clinical experience and results.METHODS: The sternal ZipFix(TM) System is based on the cable-tie principle. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22731778", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1122, "text": "In our initial evaluation, the short-term results have shown that the sternal ZipFix(TM) can be used safely and effectively. It is fast, easy to use and serves as a potential alternative for traditional wire closure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22731778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "To determine the difference in sternal infection and other infectious events between conventional wire and cable-tie-based closure techniques post-sternotomy in a collective of patients after cardiac surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23624983", "endSection": "abstract" } ] }, { "body": "Is transcription of eRNA bidirectional?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24909122", "http://www.ncbi.nlm.nih.gov/pubmed/25810254", "http://www.ncbi.nlm.nih.gov/pubmed/27066865", "http://www.ncbi.nlm.nih.gov/pubmed/23636943", "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "http://www.ncbi.nlm.nih.gov/pubmed/25934506", "http://www.ncbi.nlm.nih.gov/pubmed/24778216", "http://www.ncbi.nlm.nih.gov/pubmed/23728302" ], "ideal_answer": [ "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e.", "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers A richer picture has taken shape, integrating transcription of coding genes, enhancer RNAs (eRNAs), and various other noncoding transcriptional events.", "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs).", "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). A richer picture has taken shape, integrating transcription of coding genes, enhancer RNAs (eRNAs), and various other noncoding transcriptional events.", "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers", "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). " ], "exact_answer": "yes", "type": "yesno", "id": "5ac24f7595d0062724000003", "snippets": [ { "offsetInBeginSection": 94, "offsetInEndSection": 289, "text": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23728302", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 433, "text": "Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24778216", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 834, "text": "The distal enhancer of the gonadotropin hormone \u03b1-subunit gene, chorionic gonadotropin alpha (Cga), is responsible for Cga cell-specific expression in gonadotropes and thyrotropes, and we show here that it encodes two bidirectional nonpolyadenylated RNAs whose levels are increased somewhat by exposure to gonadotropin-releasing hormone but are not necessarily linked to Cga transcriptional activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810254", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 722, "text": "A richer picture has taken shape, integrating transcription of coding genes, enhancer RNAs (eRNAs), and various other noncoding transcriptional events. In this review we give an overview of recent studies detailing the mechanisms of RNA polymerase II (RNA Pol II)-based transcriptional initiation and discuss the ways in which transcriptional direction is established as well as its functional implications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27066865", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1064, "text": "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934506", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 833, "text": "The distal enhancer of the gonadotropin hormone \u03b1-subunit gene, chorionic gonadotropin alpha (Cga), is responsible for Cga cell-specific expression in gonadotropes and thyrotropes, and we show here that it encodes two bidirectional nonpolyadenylated RNAs whose levels are increased somewhat by exposure to gonadotropin-releasing hormone but are not necessarily linked to Cga transcriptional activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810254", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 462, "text": "Using this approach, we have defined a class of primary transcripts (eRNAs) that are transcribed uni- or bidirectionally from estrogen receptor binding sites (ERBSs) with an average transcription unit length of \u223c3-5 kb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636943", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1068, "text": "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934506", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 587, "text": "We identify 76 enhancer RNAs (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909122", "endSection": "abstract" }, { "offsetInBeginSection": 918, "offsetInEndSection": 1066, "text": "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934506", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 596, "text": "Instead, communication between promoters and enhancers can be bidirectional with promoters required to activate enhancer transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25561718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "A new paradigm has emerged in recent years characterizing transcription initiation as a bidirectional process encompassing a larger proportion of the genome than previously thought.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27066865", "endSection": "abstract" } ] }, { "body": "Is the protein pelota a ribosomal rescue factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20876129", "http://www.ncbi.nlm.nih.gov/pubmed/25061210", "http://www.ncbi.nlm.nih.gov/pubmed/27493551" ], "ideal_answer": [ "Yes, in eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation." ], "exact_answer": "yes", "type": "yesno", "id": "5ad35933133db5eb78000001", "snippets": [ { "offsetInBeginSection": 347, "offsetInEndSection": 411, "text": "a novel binding partner of the ribosome recycling protein Pelota", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25061210", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 399, "text": "n eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27493551", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 334, "text": "In eukaryotes, the protein complex of Pelota (yeast Dom34) and Hbs1 translational GTPase recognizes the stalled ribosome containing the defective mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20876129", "endSection": "abstract" } ] }, { "body": "Is CXCL7 a chemokine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28368308", "http://www.ncbi.nlm.nih.gov/pubmed/28245630" ], "ideal_answer": [ "Yes, CXCL7 is a chemokine highly expressed in platelets. " ], "exact_answer": "yes", "type": "yesno", "id": "5a9db99ffd02ddc336000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "CXCL7, a chemokine highly expressed in platelets, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28245630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 28, "text": "Chemokine CXCL7 Heterodimers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28368308", "endSection": "title" } ] }, { "body": "The TRPM2 gene is associated with development of spontaneous thromboembolism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28199210", "http://www.ncbi.nlm.nih.gov/pubmed/15708008", "http://www.ncbi.nlm.nih.gov/pubmed/18957938", "http://www.ncbi.nlm.nih.gov/pubmed/22487454", "http://www.ncbi.nlm.nih.gov/pubmed/27616276", "http://www.ncbi.nlm.nih.gov/pubmed/12765697", "http://www.ncbi.nlm.nih.gov/pubmed/26558786", "http://www.ncbi.nlm.nih.gov/pubmed/25236871", "http://www.ncbi.nlm.nih.gov/pubmed/28082421", "http://www.ncbi.nlm.nih.gov/pubmed/28970008", "http://www.ncbi.nlm.nih.gov/pubmed/16252251", "http://www.ncbi.nlm.nih.gov/pubmed/21140288", "http://www.ncbi.nlm.nih.gov/pubmed/23129587", "http://www.ncbi.nlm.nih.gov/pubmed/22475739", "http://www.ncbi.nlm.nih.gov/pubmed/20515676", "http://www.ncbi.nlm.nih.gov/pubmed/23371039" ], "ideal_answer": [ "TheTransientReceptorPotentialMelastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel andAdenosine 5'-DiphosPhataseRibose (ADPR) hydrolase function. TRPM2 is involved in Ca2+signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis and may regulate the bacteriocidal activity of Macrophages" ], "exact_answer": "no", "type": "yesno", "id": "5ab144fefcf4565872000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 533, "text": "TheTransientReceptorPotentialMelastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel andAdenosine 5'-DiphosPhataseRibose (ADPR) hydrolase function. TRPM2 is involved in Ca2+signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28199210", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 313, "text": "We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28082421", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 400, "text": "The transient receptor potential melastatin-2 (TRPM2) is an oxidative stress sensing channel that is expressed in a number of inflammatory cells and therefore it has been suggested that inhibition of TRPM2 could lead to a beneficial effect in COPD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "TRPM2 is a recently identified TRPM family cation channel which is unique among known ion channels in that it contains a C-terminal domain which is homologous to the NUDT9 ADP-ribose hydrolase and possesses intrinsic ADP-ribose hydrolase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12765697", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1859, "text": "These results suggest that TRPM2 may participate in antigen-induced extracellular Ca(2+) influx and subsequent degranulation. In addition, TRPM2 inhibitors were shown to improve food allergic reactions in a mouse model. Together, these results suggest that TRPM2 inhibitors suppress MMC degranulation via regulation of the increase in [Ca(2+)]cyt. Thus, TRPM2 may play a key role in degranulation by modulating intracellular Ca(2+) in MMCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23371039", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 287, "text": "he Na+ and Ca(2+)-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca(2+) or by hydrogen peroxide (H(2)O(2)), an experimental model for oxidative stress, binding to the channel's enzymatic Nudix domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21140288", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 471, "text": "hese alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25236871", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 868, "text": "TRPM2 (Transient Receptor Potential Melastatin 2) is a Ca2+-permeable ion channel that is activated under conditions of oxidative stress. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28970008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca2+-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27616276", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 507, "text": "Here, we describe the computational identification of a melanoma-enriched antisense transcript, TRPM2-AS, mapped within the locus of TRPM2, an ion channel capable of mediating susceptibility to cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18957938", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 576, "text": "The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26558786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable cation channel activated by ADP-ribose or reactive oxygen species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15708008", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 627, "text": " Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+ permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22487454", "endSection": "abstract" } ] }, { "body": "Is a mutation of the ZIKV's membrane protein prM responsible for the microcephaly in new-born infants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28971967" ], "ideal_answer": [ "Yes, a single mutation in the prM protein of Zika virus contributes to fetal microcephaly." ], "exact_answer": "yes", "type": "yesno", "id": "5ac0aee419833b0d7b000004", "snippets": [ { "offsetInBeginSection": 245, "offsetInEndSection": 557, "text": "Here we show that a single serine-to-asparagine substitution [Ser139\u2192Asn139(S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28971967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "A single mutation in the prM protein of Zika virus contributes to fetal microcephaly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28971967", "endSection": "title" } ] }, { "body": "What is the aim of the PhenCode database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17326095", "http://www.ncbi.nlm.nih.gov/pubmed/25385275" ], "ideal_answer": [ "PhenCode (Phenotypes for ENCODE; http://www.bx.psu.edu/phencode) is a collaborative, exploratory project to help understand phenotypes of human mutations in the context of sequence and functional data from genome projects." ], "type": "summary", "id": "5ad4f4f5133db5eb7800000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "PhenCode (Phenotypes for ENCODE; http://www.bx.psu.edu/phencode) is a collaborative, exploratory project to help understand phenotypes of human mutations in the context of sequence and functional data from genome projects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17326095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "PhenCode: connecting ENCODE data with mutations and phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17326095", "endSection": "title" }, { "offsetInBeginSection": 307, "offsetInEndSection": 474, "text": "These subsets were filtered against disease-related variants in the ClinVar, UniProtKB/Swiss-Prot, and PhenCode databases, to identify neutral or nonpathogenic cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25385275", "endSection": "abstract" } ] }, { "body": "What is the basis of the Sp3 procedure used in proteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25358341", "http://www.ncbi.nlm.nih.gov/pubmed/28948796", "http://www.ncbi.nlm.nih.gov/pubmed/27215607" ], "ideal_answer": [ "SP3, a novel technology for proteomic sample preparation using magnetic beads. SP3 provides a rapid and unbiased means of proteomic sample preparation in a single tube that facilitates ultrasensitive analysis by outperforming existing protocols in terms of efficiency, scalability, speed, throughput, and flexibility." ], "type": "summary", "id": "5ac28c0c95d006272400000a", "snippets": [ { "offsetInBeginSection": 190, "offsetInEndSection": 246, "text": "single-pot solid-phase-enhanced sample preparation (SP3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28948796", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1046, "text": "Exploiting SP3, a novel technology for proteomic sample preparation using magnetic beads, we scaled down proteome analysis to single cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27215607", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 698, "text": " here we introduce a novel protocol using paramagnetic beads, termed Single-Pot Solid-Phase-enhanced Sample Preparation (SP3). SP3 provides a rapid and unbiased means of proteomic sample preparation in a single tube that facilitates ultrasensitive analysis by outperforming existing protocols in terms of efficiency, scalability, speed, throughput, and flexibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25358341", "endSection": "abstract" } ] }, { "body": "What is \"enhancer hijacking\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27869826", "http://www.ncbi.nlm.nih.gov/pubmed/26229090", "http://www.ncbi.nlm.nih.gov/pubmed/28726821", "http://www.ncbi.nlm.nih.gov/pubmed/29059320" ], "ideal_answer": [ "Enhancer hijacking is the molecular process through which a structural variant removes or moves a TAD boundary to expose TSSs to regulatory enhancers from which they would normally be insulated." ], "type": "summary", "id": "5abc9157fcf456587200001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869826", "endSection": "title" }, { "offsetInBeginSection": 235, "offsetInEndSection": 476, "text": "Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869826", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 881, "text": "We additionally pursued cancer-type-specific analyses and uncovered IGF2 as a target for enhancer hijacking in colorectal cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869826", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 976, "text": "New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28726821", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 346, "text": " Importantly, such variants could affect enhancer regulation by changing transcription factor bindings or enhancer hijacking, and in turn, make an essential contribution to disease progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059320", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1503, "text": "We demonstrate a novel approach for simultaneous detection of genomic rearrangements and enhancer activity in tumor biopsies. We identify novel mechanisms of enhancer-driven regulation of the oncogenes MYC and BCL6, and show that the BCL6 locus can serve as an enhancer donor in an \"enhancer hijacking\" translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26229090", "endSection": "abstract" } ] }, { "body": "What disease is tinea ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16724791", "http://www.ncbi.nlm.nih.gov/pubmed/22435428", "http://www.ncbi.nlm.nih.gov/pubmed/19434960", "http://www.ncbi.nlm.nih.gov/pubmed/22512412", "http://www.ncbi.nlm.nih.gov/pubmed/8021081", "http://www.ncbi.nlm.nih.gov/pubmed/134458", "http://www.ncbi.nlm.nih.gov/pubmed/10826264", "http://www.ncbi.nlm.nih.gov/pubmed/27436771", "http://www.ncbi.nlm.nih.gov/pubmed/15788142", "http://www.ncbi.nlm.nih.gov/pubmed/25403034", "http://www.ncbi.nlm.nih.gov/pubmed/1379146", "http://www.ncbi.nlm.nih.gov/pubmed/11340482", "http://www.ncbi.nlm.nih.gov/pubmed/15050029", "http://www.ncbi.nlm.nih.gov/pubmed/19231646", "http://www.ncbi.nlm.nih.gov/pubmed/16465134", "http://www.ncbi.nlm.nih.gov/pubmed/25053979", "http://www.ncbi.nlm.nih.gov/pubmed/11990247", "http://www.ncbi.nlm.nih.gov/pubmed/12123553", "http://www.ncbi.nlm.nih.gov/pubmed/24442039" ], "ideal_answer": [ "Tinea is a superficial fungal infections of the skin." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:0050116", "http://www.disease-ontology.org/api/metadata/DOID:13074", "https://meshb.nlm.nih.gov/record/ui?ui=D014006", "https://meshb.nlm.nih.gov/record/ui?ui=D014007", "https://meshb.nlm.nih.gov/record/ui?ui=D014005", "http://www.disease-ontology.org/api/metadata/DOID:13369", "http://www.disease-ontology.org/api/metadata/DOID:0050108", "http://www.disease-ontology.org/api/metadata/DOID:8912", "https://meshb.nlm.nih.gov/record/ui?ui=D014010", "http://www.disease-ontology.org/api/metadata/DOID:4337", "https://meshb.nlm.nih.gov/record/ui?ui=D014008", "http://www.disease-ontology.org/api/metadata/DOID:0050107", "http://www.disease-ontology.org/api/metadata/DOID:0050104", "http://www.disease-ontology.org/api/metadata/DOID:12404", "http://www.disease-ontology.org/api/metadata/DOID:0050106", "https://meshb.nlm.nih.gov/record/ui?ui=D004194" ], "type": "summary", "id": "5aa67b4fd6d6b54f7900000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Onychomycosis is a common infection of the nail unit that is usually caused by a dermatophyte (tinea unguium) and most frequently affects toenails in adults", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25053979", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 729, "text": "skin infections with dermatophytes such as tinea pedis and tinea corporis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22512412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Tinea capitis is the most common dermatophyte infection in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19231646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The term \"tinea incognita\" refers to diverse clinical presentation of mycotic infections modified by inappropriate use of topical or systemic corticosteroids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15788142", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 493, "text": "Dermatophyte infections are common at all ages, in both sexes, and they have a worldwide distribution. These infections include tinea capitis, tinea cruris, tinea pedis, tinea corporis, tinea manuum and tinea barbae. Tinea versicolor, caused by Malassezia furfur,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1379146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Tinea capitis is a fungal infection of the skin and the hair with involvement of the hair shaft and the pilosebaceous unit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11990247", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 332, "text": "The genus Trichophyton gives rise to most of the tinea dermatophytoses, including tinea capitis, tinea pedis, and tinea unguium (onychomycosis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10826264", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 960, "text": " For the men, onychomycosis (nail fungus, 31.5%), tinea pedis (foot fungus, 27.8%), and acne (24.1 %) were the most commonly diagnosed skin diseases, with contact dermatitis diagnosed in 5.6% of the sample", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16724791", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "A statistical 30-year study of dermatomycosis in Sendai National Hospital (1968-1997) revealed many changes in the prevalent diseases: Tinea pedis and tinea unguium constantly increased during this period, and the ratio of the former associated with nail infection finally reached 30% of all tinea pedis patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16465134", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 490, "text": "Eighty percent of the examined boys were with unless one skin disease. Tinea capitis (42.66%), scabiosis (13.33%), pyoderma (15.33%), plantar keratodermia (100%) were the skin diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19434960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Tinea capitis is a dermatophyte infection that occurs mainly in childhood;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11340482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Tinea pedis is a chronic fungal infection of the feet, very often observed in patients who are immuno-suppressed or have diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15050029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Tinea infections are caused by dermatophytes and are classified by the involved site. The most common infections in prepubertal children are tinea corporis and tinea capitis, whereas adolescents and adults are more likely to develop tinea cruris, tinea pedis, and tinea unguium (onychomycosis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25403034", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 740, "text": "The most frequent diseases observed at arrival were dermatological conditions. Of the adoptees, 70% presented at least one skin disease, of which 57.5% were infectious; Tinea capitis being the most frequent (n\u00a0=\u00a042). The recovery rate of Tinea capitis was 89% (n\u00a0=\u00a032/36). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27436771", "endSection": "abstract" } ] }, { "body": "How are deletion breakpoints defined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15185094", "http://www.ncbi.nlm.nih.gov/pubmed/15832308", "http://www.ncbi.nlm.nih.gov/pubmed/17351135", "http://www.ncbi.nlm.nih.gov/pubmed/26028266", "http://www.ncbi.nlm.nih.gov/pubmed/16293123", "http://www.ncbi.nlm.nih.gov/pubmed/9462544", "http://www.ncbi.nlm.nih.gov/pubmed/6300765", "http://www.ncbi.nlm.nih.gov/pubmed/15944227", "http://www.ncbi.nlm.nih.gov/pubmed/27084947", "http://www.ncbi.nlm.nih.gov/pubmed/27560363", "http://www.ncbi.nlm.nih.gov/pubmed/19715670", "http://www.ncbi.nlm.nih.gov/pubmed/11336982", "http://www.ncbi.nlm.nih.gov/pubmed/1983039" ], "ideal_answer": [ "Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster. We identified 18 deletion breakpoints at the DNA nucleotide sequence level. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats.", "We identified 18 deletion breakpoints at the DNA nucleotide sequence level. Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster. In this study, we investigated the deletion breakpoints of the parkin mutations in 22 families with AR-JP and examined the possible association between these deletion events and meiotic recombinations. he hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. Specifically, (AT)n, (GAA)n and (GAAA)n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats.", "Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. A promising new workflow relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation.", "Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. ", "We identified 18 deletion breakpoints at the DNA nucleotide sequence level. Specifically, (AT)n, (GAA)n and (GAAA)n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster." ], "type": "summary", "id": "5abc9c1efcf4565872000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15185094", "endSection": "title" }, { "offsetInBeginSection": 299, "offsetInEndSection": 577, "text": "In this study, we investigated the deletion breakpoints of the parkin mutations in 22 families with AR-JP and examined the possible association between these deletion events and meiotic recombinations. We identified 18 deletion breakpoints at the DNA nucleotide sequence level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19715670", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 355, "text": "Hemizygotic deletions or duplications in the large Duchenne muscular dystrophy DMD gene responsible for Duchenne and Becker muscular dystrophies are routinely identified using multiple ligation probe amplification and array-based comparative genomic hybridization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27560363", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 652, "text": "Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27560363", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 1035, "text": "he hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27560363", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1319, "text": "Specifically, (AT)n, (GAA)n and (GAAA)n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27084947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Using this approach, we have efficiently defined the proximal and distal breakpoints in two cytogenetic cases, one duplication and one deletion, to within 5-20 kb. The results support the potential use of BAC-based PCR fragments to further improve the resolution of the microarray-CGH strategy by an order of magnitude.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15832308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The deletion breakpoints were defined by a combination of long polymerase chain reaction (PCR) amplifications, and conventional PCR and DNA sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336982", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 684, "text": "In this investigation, polymerase chain reaction (PCR)-based techniques and sequencing were used to isolate the deletion breakpoints, utilizing the newly available dog genome sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16293123", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 939, "text": "The deletion breakpoints were defined by a combination of long polymerase chain reaction (PCR) amplifications, and conventional PCR and DNA sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336982", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 841, "text": "We used paralog-specific primers and long-range PCR to clone, sequence, and examine the distal deletion breakpoints from two patients with de novo deletions mapping to these distal LCRs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17351135", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 437, "text": "To define the Thailand deletion breakpoints, we used polymerase chain reaction (PCR) to amplify the normal-sequence DNA fragments across the breakpoints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9462544", "endSection": "abstract" } ] }, { "body": "How is the nuclear localization of lncRNA mediated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24732794" ], "ideal_answer": [ "The lncRNA localization to the nucleus can be mediated by the pentamer sequence AGCCC." ], "type": "summary", "id": "5ab8fb5bfcf4565872000017", "snippets": [ { "offsetInBeginSection": 150, "offsetInEndSection": 864, "text": "As many lncRNAs regulate nuclear events and thus must localize to nuclei, we analyzed the sequence requirements for nuclear localization in an intergenic lncRNA named BORG (BMP2-OP1-responsive gene), which is both spliced and polyadenylated but is strictly localized in nuclei. Subcellular localization of BORG was not dependent on the context or level of its expression or decay but rather depended on the sequence of the mature, spliced transcript. Mutational analyses indicated that nuclear localization of BORG was mediated through a novel RNA motif consisting of the pentamer sequence AGCCC with sequence restrictions at positions -8 (T or A) and -3 (G or C) relative to the first nucleotide of the pentamer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24732794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "A novel RNA motif mediates the strict nuclear localization of a long noncoding RNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24732794", "endSection": "title" } ] }, { "body": "What is ATAC-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "http://www.ncbi.nlm.nih.gov/pubmed/29030848", "http://www.ncbi.nlm.nih.gov/pubmed/27832532", "http://www.ncbi.nlm.nih.gov/pubmed/25679813", "http://www.ncbi.nlm.nih.gov/pubmed/28075484" ], "ideal_answer": [ "The assay for transposase-accessible chromatin using sequencing (ATAC-seq) was recently established as a method to profile open chromatin, which overcomes the sample size limitations of the alternative methods DNase/MNase-seq.", "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. ", "An assay for transposase-accessible chromatin using sequencing (ATAC-seq) is based on in vitro transposition of sequencing adaptors into native chromatin. It is described as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution." ], "type": "summary", "id": "5abd31e0fcf456587200002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 840, "text": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 760, "text": "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1053, "text": "Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 840, "text": "When TFs are bound to active regulatory regions, they displace canonical nucleosomes, making these regions biochemically detectable as nucleosome-depleted regions or accessible/open chromatin. Here we ask whether open chromatin profiling can be used to identify the entire repertoire of active promoters and enhancers underlying tissue-specific gene expression during normal development and oncogenesis in vivo. To this end, we first compare two different approaches to detect open chromatin in vivo using the Drosophila eye primordium as a model system: FAIRE-seq, based on physical separation of open versus closed chromatin; and ATAC-seq, based on preferential integration of a transposon into open chromatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25679813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The assay for transposase-accessible chromatin using sequencing (ATAC-seq) was recently established as a method to profile open chromatin, which overcomes the sample size limitations of the alternative methods DNase/MNase-seq. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29030848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) is a useful method to map genome-wide chromatin accessibility and nucleosome positioning", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27832532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Assay for Transposase-Accessible Chromatin Using Sequencing (ATAC-seq) Data Analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28075484", "endSection": "title" }, { "offsetInBeginSection": 279, "offsetInEndSection": 472, "text": "requiring low numbers of living cells as input, for examining chromatin accessibility across the epigenome, known as the assay for transposase-accessible chromatin using sequencing (ATAC-seq). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28075484", "endSection": "abstract" } ] }, { "body": "What is the TALE-iD method used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27940490" ], "ideal_answer": [ "TALE-iD is a methylation-based method for the study of native chromatin structure.", "Using different cell types and loci, computational modeling, and a methylation-based orthogonal validation method, \"TALE-iD\", we show that native interactions resemble cross-linked ones, but display improved signal-to-noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topologically associating domain restrictions.", "Using different cell types and loci, computational modeling, and a methylation-based orthogonal validation method, \"TALE-iD\", we show that native interactions resemble cross-linked ones, but display improved signal-to-noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topologically associating domain restrictions. " ], "type": "summary", "id": "5a8d8f39fcd1d6a10c000024", "snippets": [ { "offsetInBeginSection": 778, "offsetInEndSection": 1139, "text": "Using different cell types and loci, computational modeling, and a methylation-based orthogonal validation method, \"TALE-iD\", we show that native interactions resemble cross-linked ones, but display improved signal-to-noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topologically associating domain restrictions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940490", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 777, "text": "We apply i3C to intact nuclei of living cells and exploit native forces that stabilize chromatin folding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940490", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1140, "text": "Using different cell types and loci, computational modeling, and a methylation-based orthogonal validation method, \"TALE-iD\", we show that native interactions resemble cross-linked ones, but display improved signal-to-noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topologically associating domain restrictions..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940490", "endSection": "abstract" } ] }, { "body": "What is Paget's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28255281", "http://www.ncbi.nlm.nih.gov/pubmed/16429324", "http://www.ncbi.nlm.nih.gov/pubmed/17447970", "http://www.ncbi.nlm.nih.gov/pubmed/27600564", "http://www.ncbi.nlm.nih.gov/pubmed/27815949", "http://www.ncbi.nlm.nih.gov/pubmed/11237774", "http://www.ncbi.nlm.nih.gov/pubmed/16899115", "http://www.ncbi.nlm.nih.gov/pubmed/12094381", "http://www.ncbi.nlm.nih.gov/pubmed/2660231", "http://www.ncbi.nlm.nih.gov/pubmed/23929251", "http://www.ncbi.nlm.nih.gov/pubmed/28339664", "http://www.ncbi.nlm.nih.gov/pubmed/15389972", "http://www.ncbi.nlm.nih.gov/pubmed/19032921", "http://www.ncbi.nlm.nih.gov/pubmed/27761746", "http://www.ncbi.nlm.nih.gov/pubmed/8873960", "http://www.ncbi.nlm.nih.gov/pubmed/18469796", "http://www.ncbi.nlm.nih.gov/pubmed/15920545", "http://www.ncbi.nlm.nih.gov/pubmed/18496141" ], "ideal_answer": [ "Paget's disease of bone (PDB) is a\u00a0noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. ", "Paget's disease of bone interferes with your body's normal recycling process, in which new bone tissue gradually replaces old bone tissue. Over time, the disease can cause affected bones to become fragile and misshapen. Mammary Paget's disease and extramammary Paget's disease are neoplastic conditions, in which there is intraepithelial (usually intraepidermal) infiltration by neoplastic cells showing glandular differentiation.", "Paget's disease of bone (PDB) is a\u00a0noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. As a\u00a0result, there is deformity and enlargement of the bone with a\u00a0defective and disorganized pattern." ], "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:5408", "https://meshb.nlm.nih.gov/record/ui?ui=D010145", "https://meshb.nlm.nih.gov/record/ui?ui=D010144" ], "type": "summary", "id": "5aa67b6ad6d6b54f79000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "Paget's disease of bone (PDB) is a\u00a0noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. As a\u00a0result, there is deformity and enlargement of the bone with a\u00a0defective and disorganized pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Paget's disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28255281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Adult PD of bone is the second commonest metabolic bone condition after osteoporosis. The condition is characterized by increased bone cell activity, with bone-resorbing osteoclasts often larger and containing more nuclei than normal, and osteoblasts producing increased amounts of disorganized bone. This leads to expanded bone of poor quality possessing both sclerotic and lytic areas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28339664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Paget's disease of bone is a\u00a0disorder of bone remodelling, leading to changes in the architecture and overall appearance of the bone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27761746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Unlike previously described cases of mammary, vulvar, and perianal Paget disease, esophageal Paget cells are almost universally associated with underlying adenocarcinoma and not with high grade dysplasia (\"in situ\" disease) or primary Paget disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18496141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Paget's disease is the most exaggerated example of bone remodeling in which abnormal osteoclastic bone resorption remains coupled to new bone formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8873960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Paget's disease of bone is characterized by the progressive and extensive replacement, in one or several bones, of normal bone tissue by a bone tissue of rough and irregular structure, the excessive and disorderly renewal of which gradually produces hyperdensity and hypertrophy of the bones involved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2660231", "endSection": "abstract" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1849, "text": "Sixty-five percent (15/23) of the Paget's disease of the breast had 50% of Paget cells expressing E-cadherin, and for plakoglobin and beta-catenin it was 17% (4/23) and 28% (6/21), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18469796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Paget disease of the vulva can be mimicked by several disease entities histopathologically, but most of these entities can be clinically distinguished from vulvar Paget disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12094381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Paget's disease is an intra-epidermal adenocarcinoma seen over the nipple/areola (mammary Paget's disease) or in extramammary body zones, such as the anogenital and perineal skin and the axilla.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17447970", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "BACKGROUND Mammary Paget's disease and extramammary Paget's disease are neoplastic conditions, in which there is intraepithelial (usually intraepidermal) infiltration by neoplastic cells showing glandular differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16899115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Mammary Paget's disease and extramammary Paget's disease are rare intraepithelial neoplasms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920545", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 241, "text": "Mammary Paget's disease is almost exclusively associated with underlying invasive breast carcinoma or high-grade ductal carcinoma in situ (DCIS G3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920545", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 186, "text": "Paget's disease is primarily a disease of the osteoclast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15389972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Paget's disease of bone is a chronic focal skeletal disorder characterized by increased bone resorption by the osteoclasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16429324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Paget's disease of bone is a focal disorder of aging bone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19032921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Paget's disease of the bone is a chronic osteopathy that leads to structural weakness, hypervascularity, and bone deformities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27815949", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Paget's disease of the breast is a disorder of the nipple-areola complex that, while rare, is often associated with an underlying carcinoma. It is characterized by eczematoid changes of the nipple.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23929251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Paget's disease of the breast is a rare disorder of the nipple-areola complex that is often associated with an underlying in situ or invasive carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11237774", "endSection": "abstract" } ] }, { "body": "What is the function of penicillinase, also known as beta lactamase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19100272", "http://www.ncbi.nlm.nih.gov/pubmed/26521981", "http://www.ncbi.nlm.nih.gov/pubmed/11453693", "http://www.ncbi.nlm.nih.gov/pubmed/16870770" ], "ideal_answer": [ "Beta-lactamases are a family of serine enzymes that hydrolyse beta-lactam antibiotics following an acylation-deacylation mechanism." ], "concepts": [ "http://www.uniprot.org/uniprot/BLAC_KLEPN", "http://www.uniprot.org/uniprot/BLAC_BACTU", "https://meshb.nlm.nih.gov/record/ui?ui=D001618", "http://www.uniprot.org/uniprot/BLAC_KITAU", "https://meshb.nlm.nih.gov/record/ui?ui=D010405", "http://www.uniprot.org/uniprot/BLAC_BACSU", "http://www.uniprot.org/uniprot/BLAC_BACAM", "http://www.uniprot.org/uniprot/BLAC_CITKO", "http://www.uniprot.org/uniprot/BLAC_AMYLA" ], "type": "summary", "id": "5aae651ffcf456587200000d", "snippets": [ { "offsetInBeginSection": 43, "offsetInEndSection": 171, "text": "eta-lactamases, a family of serine enzymes that hydrolyse beta-lactam antibiotics following an acylation-deacylation mechanism, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11453693", "endSection": "abstract" }, { "offsetInBeginSection": 64, "offsetInEndSection": 106, "text": "\u03b2-lactamase-mediated antibiotic resistance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26521981", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 469, "text": "beta-lactamases hydrolyze penicillins very fast,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19100272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "beta-Lactam antibiotics are extremely effective in disrupting the synthesis of the bacterial cell wall in both gram-positive and gram-negative bacteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16870770", "endSection": "abstract" } ] }, { "body": "The common house cat, Felis silvestris catus and the domestic dog, Canis familiaris both belong to what taxonomic order?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16772461" ], "ideal_answer": [ "Domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora. ", "The common house cat and domestic dog both belong to the order Carnivora in the class Mammalia", "domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora. ", "domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora." ], "exact_answer": [ "Carnivora" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004285", "https://meshb.nlm.nih.gov/record/ui?ui=D000829", "https://meshb.nlm.nih.gov/record/ui?ui=D002415" ], "type": "factoid", "id": "5ab1483bfcf4565872000014", "snippets": [ { "offsetInBeginSection": 53, "offsetInEndSection": 157, "text": "domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16772461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The dentition, sense of taste and meal patterning of domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16772461", "endSection": "abstract" } ] }, { "body": "What is caused by the ectopic expression of CTCF?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28862757", "http://www.ncbi.nlm.nih.gov/pubmed/15941718", "http://www.ncbi.nlm.nih.gov/pubmed/28161276", "http://www.ncbi.nlm.nih.gov/pubmed/26268681", "http://www.ncbi.nlm.nih.gov/pubmed/11507042", "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "http://www.ncbi.nlm.nih.gov/pubmed/14980504", "http://www.ncbi.nlm.nih.gov/pubmed/21870268", "http://www.ncbi.nlm.nih.gov/pubmed/21465478", "http://www.ncbi.nlm.nih.gov/pubmed/9591631" ], "ideal_answer": [ "ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage;", "Enforced ectopic expression of CTCF inhibits cell growth in culture. ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage;", "Ectopic expression of CTCF results in severe cell growth inhibition at multiple points within the cell cycle.", "ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage;. ", "Enforced ectopic expression of CTCF inhibits cell growth in culture." ], "type": "summary", "id": "5abcf6b9fcf4565872000027", "snippets": [ { "offsetInBeginSection": 852, "offsetInEndSection": 920, "text": "Enforced ectopic expression of CTCF inhibits cell growth in culture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9591631", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 656, "text": "Here we show that ectopic expression of CTCF in many cell types inhibits cell clonogenicity by causing profound growth retardation without apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11507042", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 381, "text": "Ectopic expression of CTCF results in severe cell growth inhibition at multiple points within the cell cycle, indicating that CTCF levels must be stringently monitored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14980504", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 767, "text": "ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15941718", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 310, "text": "Ectopic expression of CTCF in various normal and tumoral human cell lines inhibits cell division and clonogenicity, with the consequence to consider CTCF a potential tumor-suppressor factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21465478", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 1065, "text": "Depletion of the BORIS gene leads to altered transcription of a large number of genes and the differentiation of K562 cells, while the ectopic expression of this CTCF paralog leads to specific changes in transcription in MCF7 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268681", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1219, "text": "The role of GATA-1 in interaction between CTCF sites was revealed by its ectopic expression in 293 cells and by deletion of a GATA-1 site in the LCR HS2. These findings indicate that erythroid specific activator GATA-1 acts at CTCF sites around the \u03b2-globin locus to establish tissue-specific chromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28161276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "By using these model systems we demonstrated that: (i) ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage; (ii) CTCF knock-down significantly inhibited differentiation of K562 cells into erythroid lineage; (iii) differentiation of K562 into the megakaryocytic lineage was not significantly affected; and (iv) down-regulation of MYC has been identified as one of the mechanisms by which CTCF promotes erythroid differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15941718", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 505, "text": "To determine how these varying effects would integrate in vivo, we engineered a variety of expression systems to study effects of CTCF on cell growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11507042", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 655, "text": "Here we show that ectopic expression of CTCF in many cell types inhibits cell clonogenicity by causing profound growth retardation without apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11507042", "endSection": "abstract" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1315, "text": "While MYC is the well-characterized CTCF target, the inhibitory effects of CTCF on cell growth could not be ascribed solely to repression of MYC, suggesting that additional CTS-driven genes involved in growth-regulatory circuits, such as p19ARF, are likely to contribute to CTCF-induced growth arrest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11507042", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 783, "text": "Deletion of the CTCF-cohesin binding site caused an inhibition of cell growth and viral genome instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 1087, "text": "By using these model systems we demonstrated that: (i) ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage; (ii) CTCF knock-down significantly inhibited differentiation of K562 cells into erythroid lineage; (iii) differentiation of K562 into the megakaryocytic lineage was not significantly affected; and (iv) down-regulation of MYC has been identified as one of the mechanisms by which CTCF promotes erythroid differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15941718", "endSection": "abstract" } ] }, { "body": "What is the dardarin protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22988875", "http://www.ncbi.nlm.nih.gov/pubmed/20624856", "http://www.ncbi.nlm.nih.gov/pubmed/26600626", "http://www.ncbi.nlm.nih.gov/pubmed/28205494", "http://www.ncbi.nlm.nih.gov/pubmed/24225420", "http://www.ncbi.nlm.nih.gov/pubmed/20722494" ], "ideal_answer": [ "Mutations in the leucine-rich repeat kinase 2 gene (LRRK2 or Dardarin) are considered to be a common cause of autosomal dominant and sporadic Parkinson\u00b4s disease," ], "type": "summary", "id": "5ac0fccf19833b0d7b000007", "snippets": [ { "offsetInBeginSection": 471, "offsetInEndSection": 487, "text": "LRRK2 (dardarin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28205494", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 240, "text": "Mutations in the leucine-rich repeat kinase 2 gene (LRRK2 or Dardarin) are considered to be a common cause of autosomal dominant and sporadic Parkinson\u00b4s disease, but the prevalence of these mutations varies among populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26600626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson's disease (PD);", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Mutations in LRRK2 (leucine-rich repeat kinase 2) (also known as PARK8 or dardarin) are responsible for the autosomal-dominant form of PD (Parkinson's disease). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22988875", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 184, "text": "Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2; PARK8) encoding dardarin, implicated in patients with autosomal dominant and sporadic Parkinson's disease (PD) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20722494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Missense mutations in leucine-rich repeat kinase 2 (LRRK2)/Dardarin gene, the product of which encodes a kinase with multiple domains, are known to cause autosomal dominant late onset Parkinson's disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20624856", "endSection": "abstract" } ] }, { "body": "In which syndrome is the RPS19 gene most frequently mutated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20606162", "http://www.ncbi.nlm.nih.gov/pubmed/29044489", "http://www.ncbi.nlm.nih.gov/pubmed/24675553", "http://www.ncbi.nlm.nih.gov/pubmed/18768533", "http://www.ncbi.nlm.nih.gov/pubmed/23990987", "http://www.ncbi.nlm.nih.gov/pubmed/12718904", "http://www.ncbi.nlm.nih.gov/pubmed/23257444", "http://www.ncbi.nlm.nih.gov/pubmed/17053056", "http://www.ncbi.nlm.nih.gov/pubmed/12586610", "http://www.ncbi.nlm.nih.gov/pubmed/17082006", "http://www.ncbi.nlm.nih.gov/pubmed/15523650", "http://www.ncbi.nlm.nih.gov/pubmed/26447946", "http://www.ncbi.nlm.nih.gov/pubmed/17186470", "http://www.ncbi.nlm.nih.gov/pubmed/17376718", "http://www.ncbi.nlm.nih.gov/pubmed/11424144", "http://www.ncbi.nlm.nih.gov/pubmed/12351378" ], "ideal_answer": [ "Ribosomal protein S19 (RPS19), currently the only gene associated with DBA, is mutated in 25% of DBA patients, but its role in erythropoiesis is unknown. ", "Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands. Mutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families.", "Among these patients, RPS19 was the most frequently mutated gene. It has been proven that defects of ribosomal proteins can lead to this disease and that RPS19 is the most frequently mutated gene in DBA patients. Mutations in the ribosomal protein S19 gene (RPS19) have been found in 25% of patients with Diamond-Blackfan anemia, a rare syndrome of congenital bone marrow failure characterized by erythroblastopenia and various malformations. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. Analysis of pre-rRNA processing in primary DBA lymphoblastoid cell lines demonstrated similar alterations of large ribosomal subunit rRNA in both RPL35A-mutated and some RPL35A wild-type patients, suggesting additional large ribosomal subunit gene defects are likely present in some cases of DBA. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. Recent reports show that the ribosomal protein S19 (RPS19) gene is mutated in 25% of all patients with DBA.", "The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups.", "Mutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families. Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands." ], "exact_answer": [ "Diamond-Blackfan Anemia", "DBA" ], "type": "factoid", "id": "5a896c26fcd1d6a10c000007", "snippets": [ { "offsetInBeginSection": 475, "offsetInEndSection": 594, "text": "The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29044489", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 344, "text": "Twenty-one cases of DBA admitted in our hospital from Dec 2008 to Aug 2012 were screened by PCR for mutations in the nine known genes associated with DBA: RPS19, RPS24, RPS17, RPL5, RPL11, RPS7, RPL35a, RPS10 and RPS26", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257444", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 603, "text": "The results found that 8 patients (38.1%) with DBA had mutations in the genes coding for ribosomal protein, in which RPS19 mutation was identified in 3 patients, RPS24, RPS7, RPL5, RPL11 and RPL35A mutations were identified respectively in 1 of the patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257444", "endSection": "abstract" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1090, "text": "The hypospadias can be observed in some patients with RPS19 mutation and some dactyl anomalies are associated with RPL11 and RPL5 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23257444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20606162", "endSection": "title" }, { "offsetInBeginSection": 140, "offsetInEndSection": 259, "text": "Mutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20606162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17186470", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 404, "text": "Ribosomal protein S19 (RPS19), currently the only gene associated with DBA, is mutated in 25% of DBA patients, but its role in erythropoiesis is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17082006", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1035, "text": "Since a fraction of DBA patients have a deficiency in ribosomal protein S19 (RPS19), we constructed lentiviral vectors containing the RPS19 gene for overexpression in hematopoietic progenitors from RPS19-deficient DBA patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12718904", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 439, "text": "DBA is a heterogeneous disorder, caused in about 25% of cases by heterozygous mutations in the RPS19 gene (DBA1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11424144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Mutations in the ribosomal protein S19 gene (RPS19) have been found in 25% of patients with Diamond-Blackfan anemia, a rare syndrome of congenital bone marrow failure characterized by erythroblastopenia and various malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18768533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "The gene encoding the small subunit ribosomal protein 19 (RPS19) is mutated in about 25% of cases of the bone marrow failure syndrome Diamond Blackfan Anemia (DBA), a childhood disease characterized by failure of red cell production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17376718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome that is characterized by pure red-cell aplasia and associated physical deformities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23990987", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15523650", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Mutations in the ribosomal protein (RP)S19 gene have been found in about 25% of the cases of Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia that includes variable physical malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15523650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17053056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "BACKGROUND Mutations in the ribosomal protein S19 gene (RPS19) have been found in 25% of patients with Diamond-Blackfan anemia, a rare syndrome of congenital bone marrow failure characterized by erythroblastopenia and various malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18768533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12586610", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 525, "text": "By applying EMSA and ChIP methodologies in mouse erythroleukemia cells we show that GATA1 and PU.1 bind in vitro and in vivo the proximal promoter region of the RPS19 gene which is frequently mutated in Diamond-Blackfan Anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26447946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12351378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, associated physical malformations and a predisposition to cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24675553", "endSection": "abstract" } ] }, { "body": "What type of sequences do enhancers evolve from?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24097306", "http://www.ncbi.nlm.nih.gov/pubmed/28527813", "http://www.ncbi.nlm.nih.gov/pubmed/25635462", "http://www.ncbi.nlm.nih.gov/pubmed/21783031", "http://www.ncbi.nlm.nih.gov/pubmed/24218638", "http://www.ncbi.nlm.nih.gov/pubmed/24218631", "http://www.ncbi.nlm.nih.gov/pubmed/24218635" ], "ideal_answer": [ "Studies have identified enhancers that were pivotal for morphological divergence and highlighted how novel genetic networks shaping form emerged from pre-existing ones.Most of the recently evolved enhancers arise from ancestral dna exaptation , rather than lineage-specific expansions of repeat elements.", "Recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements.", "Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. The sequences of some gene regulatory elements diverge considerably, even between closely related species. ", "The trend is one of high divergence of cis-regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements." ], "exact_answer": [ "exaptation of ancestral DNA" ], "type": "factoid", "id": "5ac37afc0340b9f058000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The sequences of some gene regulatory elements diverge considerably, even between closely related species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21783031", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1031, "text": "The trend is one of high divergence of cis-regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218635", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 855, "text": "These studies have identified enhancers that were pivotal for morphological divergence and highlighted how novel genetic networks shaping form emerged from pre-existing ones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28527813", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 600, "text": "Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635462", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 804, "text": "santomea enhancer activity evolved from a weak ancestral activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218638", "endSection": "abstract" } ] }, { "body": "What nerve is involved in carpal tunnel syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28718333", "http://www.ncbi.nlm.nih.gov/pubmed/18683528", "http://www.ncbi.nlm.nih.gov/pubmed/28582584", "http://www.ncbi.nlm.nih.gov/pubmed/1888865", "http://www.ncbi.nlm.nih.gov/pubmed/7594983", "http://www.ncbi.nlm.nih.gov/pubmed/28447963", "http://www.ncbi.nlm.nih.gov/pubmed/22215765", "http://www.ncbi.nlm.nih.gov/pubmed/26330845", "http://www.ncbi.nlm.nih.gov/pubmed/28594494", "http://www.ncbi.nlm.nih.gov/pubmed/28091439", "http://www.ncbi.nlm.nih.gov/pubmed/25630774" ], "ideal_answer": [ "Carpal tunnel syndrome (CTS) is a focal compressive neuropathy of the median nerve at the level of the wrist.", "Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel.", "Carpal tunnel syndrome (CTS) is a focal compressive neuropathy of the median nerve at the level of the wrist. " ], "exact_answer": [ "median" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D020423", "https://meshb.nlm.nih.gov/record/ui?ui=D002349", "https://meshb.nlm.nih.gov/record/ui?ui=D009408", "http://www.disease-ontology.org/api/metadata/DOID:12169", "http://www.disease-ontology.org/api/metadata/DOID:573" ], "type": "factoid", "id": "5abcf010fcf4565872000023", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 154, "text": "In this study, it was aimed to determine whether median nerve epineurectomy is beneficial in the surgical management of carpal tunnel syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28091439", "endSection": "abstract" }, { "offsetInBeginSection": 1629, "offsetInEndSection": 1769, "text": "We believe that median nerve epineurectomy is unnecessary in the surgical management of primary CTS since it has no influence on the midterm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28091439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Carpal tunnel syndrome (CTS) is a focal compressive neuropathy of the median nerve at the level of the wrist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28594494", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1310, "text": " CTS, which may occur in as many as 25% of patients who undergo carpal tunnel release, most commonly results from an incomplete transverse carpal ligament release or an incorrect initial diagnosis. Patients with recurrent symptoms often have perineural fibrosis that tethers the median nerve.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28594494", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 111, "text": " Ultrasound is an established method of viewing the median nerve in the carpal tunnel syndrome (CTS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28582584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The carpal tunnel syndrome is a neuropathy due to trapping (focal lesion of the peripheral nerve due to a local cause); in this case, the median nerve is the most commonly involved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1888865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Carpal tunnel syndrome is a complex of symptoms as a result of compression of the median nerve in the carpal tunnel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18683528", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 267, "text": "To define the relationship between body indices of healthy adults and cross-sectional areas of the carpal tunnel and median nerve and to obtain the nerve/tunnel index, which represents a new standard for diagnosing carpal tunnel syndrome using sonography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22215765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Restricted motion of the median nerve in carpal tunnel syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7594983", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Carpal tunnel syndrome (CTS) is the most common median nerve neuropathy, accounting for 90% of all neuropathies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25630774", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 143, "text": "Compression of the median nerve at the wrist, or carpal tunnel syndrome, is the most commonly recognized nerve entrapment syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28718333", "endSection": "abstract" } ] }, { "body": "What is the function of LOX proteins in the ECM?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26780438", "http://www.ncbi.nlm.nih.gov/pubmed/25146937", "http://www.ncbi.nlm.nih.gov/pubmed/26582054", "http://www.ncbi.nlm.nih.gov/pubmed/28668305", "http://www.ncbi.nlm.nih.gov/pubmed/26024311", "http://www.ncbi.nlm.nih.gov/pubmed/28273952" ], "ideal_answer": [ "Lysyl oxidases (LOX) are copper-dependent enzymes that oxidize primary amine substrates to reactive aldehydes. The best-studied role of LOX enzymes is the remodeling of the extracellular matrix (ECM) in animals by cross-linking collagens and elastin" ], "exact_answer": [ "The best-studied role of LOX enzymes is the remodeling of the extracellular matrix (ECM) in animals by cross-linking collagens and elastin." ], "type": "factoid", "id": "5ad243e30340b9f058000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Extracellular matrix (ECM) composition and stiffness are major driving forces for the development and persistence of fibrotic diseases. Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28273952", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 174, "text": "collagen cross-linking enzyme, lysyl oxidase (LOX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28668305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "A hallmark of heart failure (HF) is adverse extracellular matrix (ECM) remodeling, which is regulated by the collagen cross-linking enzyme, lysyl oxidase (LOX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26582054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Lysyl oxidase (LOX) is an extracellular matrix (ECM)-modifying enzyme that has been involved in cardiovascular remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26780438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Lysyl oxidases (LOX) are copper-dependent enzymes that oxidize primary amine substrates to reactive aldehydes. The best-studied role of LOX enzymes is the remodeling of the extracellular matrix (ECM) in animals by cross-linking collagens and elastin, although intracellular functions have been reported as well. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26024311", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 285, "text": "LOXL2 is proposed to function similarly to LOX in the extracellular matrix (ECM) by promoting crosslinking of collagen and elastin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25146937", "endSection": "abstract" } ] }, { "body": "Please list 3 diseases treated with Valtrex(valacyclovir)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25749332", "http://www.ncbi.nlm.nih.gov/pubmed/8593015", "http://www.ncbi.nlm.nih.gov/pubmed/22670895", "http://www.ncbi.nlm.nih.gov/pubmed/15482124", "http://www.ncbi.nlm.nih.gov/pubmed/16771614", "http://www.ncbi.nlm.nih.gov/pubmed/14505192", "http://www.ncbi.nlm.nih.gov/pubmed/15550990", "http://www.ncbi.nlm.nih.gov/pubmed/15989601", "http://www.ncbi.nlm.nih.gov/pubmed/11772333", "http://www.ncbi.nlm.nih.gov/pubmed/12556212" ], "ideal_answer": [ "Valtrex (valacyclovir) is an antiviral medication used to treat infections with: herpes zoster (shingles), herpes simplex genitalis (genital herpes),\nand herpes labialis (cold sores)." ], "exact_answer": [ [ "Herpes zoster or Shingles" ], [ "Herpes genitalis, or genital herpes" ], [ "Herpes labialis or cold sores" ] ], "concepts": [ "http://www.biosemantics.org/jochem#4273236", "http://www.biosemantics.org/jochem#4265772" ], "type": "list", "id": "5abcf755fcf4565872000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Valaciclovir (Valtrex, Zelitrex), the L-valine ester of aciclovir, increases aciclovir bioavailability by 3- to 5-fold over that achievable with oral aciclovir. It addresses many unmet needs of currently available anti-herpesvirus therapie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15989601", "endSection": "abstract" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1550, "text": "In controlled clinical trials in herpes zoster, valaciclovir (1000 mg three times daily) is superior to aciclovir in speeding the resolution of zoster-associated pain and post-herpetic neuralgia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15989601", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1403, "text": "alacyclovir is the only antiviral drug approved for a once-daily dose of suppressive therapy for genital herpes, as well as the only antiviral drug US FDA approved for a 3-day regimen of episodic treatment of recurrent genital herpes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16771614", "endSection": "abstract" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1568, "text": "valacyclovir is also indicated in the reduction of the sexual transmission of herpes simplex virus infection and for the treatment of herpes labialis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16771614", "endSection": "abstract" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1784, "text": "n herpes zoster, valacyclovir is more effective than acyclovir or placebo (and as equally effective as famciclovir) in shortening the length and severity of herpes zoster-associated pain and postherpetic neuralgia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16771614", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 823, "text": "valacyclovir and famciclovir are efficacious and safe for the treatment of the first episode and recurrent genital herpes and are useful as suppressive therapy for individuals with frequent genital herpes recurrences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15482124", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1073, "text": "valacyclovir and famciclovir have been shown to speed the healing of herpes zoster, and data suggests that these agents also decrease associated acute and chronic pain in people of 50 years of age or older.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15482124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Valaciclovir (Valtrex), the L-valyl ester of acyclovir, is undergoing clinical development for the treatment and suppression of herpesviral diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8593015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Valacyclovir is frequently prescribed to the elderly to treat diseases such as herpes zoster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25749332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22670895", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 702, "text": "Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex, a highly bioavailable prodrug of acyclovir (Zovirax, and famciclovir (Famvir), a highly bioavailable prodrug of penciclovir (Denavir).
OBJECTIVE: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14505192", "endSection": "abstract" }, { "offsetInBeginSection": 1014, "offsetInEndSection": 1228, "text": "In herpes zoster, valacyclovir is as effective as famciclovir and more effective than either placebo or acyclovir at facilitating cutaneous healing and healing of zoster-associated pain and post-herpetic neuralgia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772333", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 685, "text": "OBJECTIVE: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14505192", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1536, "text": "Valacyclovir is well tolerated, with convenient dosing frequencies for the treatment of genital herpes or herpes zoster, it also has the option for use as a short course therapy in the episodic treatment of recurrent genital herpes, all of which are important benefits in the management of these conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772333", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 620, "text": "Acyclovir (Zoviraxr, GlaxoSmithKline), valacyclovir (Valtrex, GlaxoSmithKline) or famciclovir (Famvir, Novartis) can be used to treat herpes zoster, and all three have been shown to reduce the duration of the herpetic rash and zoster-associated pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15550990", "endSection": "abstract" } ] }, { "body": "Which olfactory gene senses androsterone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9566734", "http://www.ncbi.nlm.nih.gov/pubmed/20836008", "http://www.ncbi.nlm.nih.gov/pubmed/17013929", "http://www.ncbi.nlm.nih.gov/pubmed/22977065", "http://www.ncbi.nlm.nih.gov/pubmed/22362865" ], "ideal_answer": [ "A previously reported association between the olfactory receptor or7d4 and the androstenone was not detected until we specifically typed this gene p = 1.1 \u00d7 10 -4.Any mammals can decipher these scent codes to discern the gender , age , endocrine status , social status , and genotype of conspecifics using dedicated sensory receptors in their olfactory system.", "These findings suggest that 1) the perceived intensity of some but not all odorants is a heritable trait, 2) use of a current genome-wide marker panel did not detect a known olfactory genotype-phenotype association, and 3) person-to-person differences in androstenone perception are influenced by OR7D4 genotype and perhaps by variants of other genes. A previously reported association between the olfactory receptor OR7D4 and the androstenone was not detected until we specifically typed this gene (P = 1.1 \u00d7 10(-4)). any mammals can decipher these scent codes to discern the gender, age, endocrine status, social status, and genotype of conspecifics using dedicated sensory receptors in their olfactory system. ", "Person-to-person differences in androstenone perception are influenced by OR7D4 genotype and perhaps by variants of other genes.", "These findings suggest that 1) the perceived intensity of some but not all odorants is a heritable trait, 2) use of a current genome-wide marker panel did not detect a known olfactory genotype-phenotype association, and 3) person-to-person differences in androstenone perception are influenced by OR7D4 genotype and perhaps by variants of other genes. " ], "exact_answer": [ "OR7D4" ], "type": "factoid", "id": "5ace17c30340b9f058000009", "snippets": [ { "offsetInBeginSection": 110, "offsetInEndSection": 303, "text": "any mammals can decipher these scent codes to discern the gender, age, endocrine status, social status, and genotype of conspecifics using dedicated sensory receptors in their olfactory system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20836008", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 688, "text": "A previously reported association between the olfactory receptor OR7D4 and the androstenone was not detected until we specifically typed this gene (P = 1.1 \u00d7 10(-4)). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362865", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1226, "text": "These findings suggest that 1) the perceived intensity of some but not all odorants is a heritable trait, 2) use of a current genome-wide marker panel did not detect a known olfactory genotype-phenotype association, and 3) person-to-person differences in androstenone perception are influenced by OR7D4 genotype and perhaps by variants of other genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362865", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 1015, "text": "The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22977065", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 688, "text": "A previously reported association between the olfactory receptor OR7D4 and the androstenone was not detected until we specifically typed this gene (P = 1.1 \u00d7 10(-4)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22362865", "endSection": "abstract" } ] }, { "body": "Where in the body would the navicular bone be found?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28295608", "http://www.ncbi.nlm.nih.gov/pubmed/28099198" ], "ideal_answer": [ "The navicular bone is located in the foot" ], "exact_answer": [ "foot" ], "type": "factoid", "id": "5abd13e1fcf4565872000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "The accessory navicular (AN) is an accessory ossicle anatomically located on the medial side of the foot, proximal to the navicular and continuous with the tibialis posterior tendon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28295608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "A 16-year-old boy developed left foot pain of unknown cause that was unresponsive to conservative treatment, associated with fever and difficulty walking. He was admitted to our hospital with osteomyelitis of the accessory and body of the navicular bone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28099198", "endSection": "abstract" } ] }, { "body": "Name an lncRNA associated with dilated cardiomyopathy.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28430627" ], "ideal_answer": [ "The lncRNA H19 is significantly upregulated in the myocardial tissue in dilated cardiomyopathy." ], "exact_answer": [ "lncRNA H19" ], "type": "factoid", "id": "5ac716810340b9f058000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "In the previous study, we generated a rat model of dilated cardiomyopathy (DCM) induced by adriamycin and found that the expression of lncRNA H19 was significantly upregulated in myocardial tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The long non-coding RNA H19 promotes cardiomyocyte apoptosis in dilated cardiomyopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430627", "endSection": "title" } ] }, { "body": "Which gene is responsible for red hair?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11689486", "http://www.ncbi.nlm.nih.gov/pubmed/7581459", "http://www.ncbi.nlm.nih.gov/pubmed/10885670", "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "http://www.ncbi.nlm.nih.gov/pubmed/19016241", "http://www.ncbi.nlm.nih.gov/pubmed/27755135", "http://www.ncbi.nlm.nih.gov/pubmed/17147521", "http://www.ncbi.nlm.nih.gov/pubmed/28024137", "http://www.ncbi.nlm.nih.gov/pubmed/22140526", "http://www.ncbi.nlm.nih.gov/pubmed/11030758", "http://www.ncbi.nlm.nih.gov/pubmed/28030792", "http://www.ncbi.nlm.nih.gov/pubmed/16704453", "http://www.ncbi.nlm.nih.gov/pubmed/15972726", "http://www.ncbi.nlm.nih.gov/pubmed/19571053", "http://www.ncbi.nlm.nih.gov/pubmed/9487023", "http://www.ncbi.nlm.nih.gov/pubmed/18484624", "http://www.ncbi.nlm.nih.gov/pubmed/23146638", "http://www.ncbi.nlm.nih.gov/pubmed/12876664", "http://www.ncbi.nlm.nih.gov/pubmed/21108681", "http://www.ncbi.nlm.nih.gov/pubmed/11254446", "http://www.ncbi.nlm.nih.gov/pubmed/11549109" ], "ideal_answer": [ "Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.", "Red hair is the null phenotype of MC1R. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to phaeomelanin production, resulting in a red or yellow coat colour. ", "Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair.", "Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Individuals with red hair have a predominance of phaeomelain in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from UVR." ], "exact_answer": [ "Melanocortin 1 receptor", "MC1R" ], "type": "factoid", "id": "5ace19420340b9f05800000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7581459", "endSection": "title" }, { "offsetInBeginSection": 380, "offsetInEndSection": 847, "text": "Individuals with red hair have a predominance of phaeomelain in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from UVR. In mammals the relative proportions of phaeomelanin and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts via its receptor (MC1R), on melanocytes, to increase the synthesis of eumelanin and the product of the agouti locus which antagonises this action", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7581459", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1492, "text": "Our findings suggest that in humans, as in other mammals, the MC1R is a control point in the regulation of pigmentation phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7581459", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 861, "text": "In humans, melanocortin 1 receptor variants are associated with red hair and fair skin, and work in progress from our laboratory suggests that certain melanocortin 1 receptor variants may preferentially be associated with hair color rather than skin type. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9487023", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 307, "text": "Red hair in man is due to certain loss of function mutations of one of the peptide products of the pro-opiomelanocortin (POMC) gene, the melanocortin-1 receptor (MC1R, MIM 155555)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17147521", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 678, "text": "This paper reviews the path of discovery of the MC1R in control of animal coat colour, the subsequent role of MC1R in human physiology and possibly wider role of MC1R in human skin carcinogenesis and human development through history.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17147521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11254446", "endSection": "title" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1161, "text": "A strong association between MC1R gene variants and fair skin and red hair was established, especially the variants Arg151Cys and Arg160Trp (P<.0001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11254446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11254446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Sequence polymorphism in the human melanocortin 1 receptor gene as an indicator of the red hair phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "We describe a minisequencing protocol for screening DNA samples for the presence of 12 mutations in the human melanocortin 1 receptor gene (MC1R), eight of which are associated with the red hair phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 574, "text": "We report the frequencies of MC1R variants in the British red haired population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "The melanocortin 1 receptor (MC1R): more than just red hair.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10885670", "endSection": "title" }, { "offsetInBeginSection": 124, "offsetInEndSection": 278, "text": " Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to phaeomelanin production, resulting in a red or yellow coat colour. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10885670", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 767, "text": "The majority of red-heads (red-haired persons) are compound heterozygotes or homozygotes for up to five frequent loss-of-function mutations. A minority of redheads are, however, only heterozygote. The MC1R is, therefore, a major determinant of sun sensitivity and a genetic risk factor for melanoma and non-melanoma skin cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10885670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15972726", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "The human melanocortin-1 receptor gene (MC1R) encodes a G-protein coupled receptor that is primarily expressed on melanocytes, where it plays a key role in pigmentation regulation. Variant alleles are associated with red hair colour and fair skin, known as the RHC phenotype, as well as skin cancer risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15972726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Red hair is the null phenotype of MC1R.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18484624", "endSection": "title" }, { "offsetInBeginSection": 162, "offsetInEndSection": 297, "text": "The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18484624", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1671, "text": "The association signals at the MC1R gene locus from CDH were uniformly more significant than traditional GWA analyses (the most significant P for CDH\u200a=\u200a3.11\u00d710\u207b\u00b9\u2074\u00b2 vs. P for rs258322\u200a=\u200a1.33\u00d710\u207b\u2076\u2076). The CDH test will contribute towards finding rare LOF variants in GWAS and sequencing studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22140526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The MC1R gene plays a crucial role in pigmentation synthesis. Loss-of-function MC1R variants, which impair protein function, are associated with red hair color (RHC) phenotype and increased skin cancer risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28030792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Genetic analysis of melanocortin 1 receptor red hair color variants in a Russian population of Eastern Siberia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27755135", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Mutations in the P gene were responsible for classic phenotype of oculocutaneous albinism type 2 (OCA2) in all eight, and mutations in the MC1R gene were responsible for the red (rather than yellow/blond) hair in the six of eight who continued to have red hair after birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12876664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Sequence variation in the melanocortin-1 receptor (MC1R) gene is associated with red hair in the normal population, but red hair is unusual in OCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12876664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "In humans, loss-of-function MC1R mutations cause fair skin, freckling, red hair, and increased predisposition to melanoma; in mice, Mc1r loss-of-function is responsible for the recessive yellow mutation, associated with pheomelanic hair and a decreased number of epidermal melanocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16704453", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 775, "text": "Sequence variation in the melanocortin-1 receptor (MC1R) gene is associated with red hair in the normal population, but red hair is unusual in OCA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12876664", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1114, "text": "Mutations in the P gene were responsible for classic phenotype of oculocutaneous albinism type 2 (OCA2) in all eight, and mutations in the MC1R gene were responsible for the red (rather than yellow/blond) hair in the six of eight who continued to have red hair after birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12876664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18484624", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 417, "text": "We show that a mouse bacterial artificial chromosome (BAC) which contains Mc1r will efficiently rescue loss of Mc1r in transgenic mice, and that overexpression of the receptor suppresses the effect of the endogenous antagonist, agouti protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11689486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11030758", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Variants of the melanocortin 1 receptor (MC1R) gene are common in individuals with red hair and fair skin, but the relative contribution to these pigmentary traits in heterozygotes, homozygotes and compound heterozygotes for variants at this locus from the multiple alleles present in Caucasian populations is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11030758", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 190, "text": "A specific variant of MC1R gene (R allele) is responsible for the red hair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28024137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "BACKGROUND Red hair color is caused by variants of the melanocortin-1 receptor (MC1R) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571053", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 706, "text": "Red hair individuals are usually compound heterozygotes or homozygous for one of a number of MC1R polymorphisms associated with red hair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11549109", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 568, "text": "Variants of the Melanocortin 1 Receptor (MC1R) gene have been found to be associated with red hair and fair skin in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11549109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "We describe a minisequencing protocol for screening DNA samples for the presence of 12 mutations in the human melanocortin 1 receptor gene (MC1R), eight of which are associated with the red hair phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 277, "text": "The genetic basis for red hair involves specific mutations, red hair color (RHC) alleles, in the melanocortin-1 receptor (MC1R) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146638", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 441, "text": "In humans, loss-of-function MC1R mutations cause fair skin, freckling, red hair, and increased predisposition to melanoma; in mice, Mc1r loss-of-function is responsible for the recessive yellow mutation, associated with pheomelanic hair and a decreased number of epidermal melanocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16704453", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 412, "text": "A multiplex PCR and a multiplex single base extension protocol were established for genotyping six exonic MC1R variations highly penetrant for red hair (R), four exonic MC1R variations weakly penetrant for red hair (r), two frameshift variations highly penetrant for red hair (R) and three variations in the promoter region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19016241", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 633, "text": "We have investigated 174 individuals from 11 large kindreds with a preponderance of red hair and an additional 99 unrelated redheads, for MC1R variants and have confirmed that red hair is usually inherited as a recessive characteristic with the R151C, R160W, D294H, R142H, 86insA and 537insC alleles at this locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11030758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Melanocortin receptor 1 (MC1R) and agouti signaling protein (ASIP) are two major genes affecting coat color phenotypes in mammals, and inactivation mutations in the MC1R gene are responsible for red coat color in European pig breeds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21108681", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 788, "text": "No loss-of-function mutation in MC1R responsible for red coat color in European breeds was observed in this breed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21108681", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 264, "text": "The genetic basis for red hair involves specific mutations, red hair color (RHC) alleles, in the melanocortin-1 receptor (MC1R) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23146638", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1280, "text": "In conclusion, no functional variant responsible for brownish red coloration was found in the coding region of MC1R and ASIP in Tibetan pigs..", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21108681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Red hair color is caused by variants of the melanocortin-1 receptor (MC1R) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19571053", "endSection": "abstract" } ] }, { "body": "Which bacteria was EcoRI, restriction endonuclease isolated from?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2996987", "http://www.ncbi.nlm.nih.gov/pubmed/6099579", "http://www.ncbi.nlm.nih.gov/pubmed/3025706", "http://www.ncbi.nlm.nih.gov/pubmed/349563" ], "ideal_answer": [ "Among hundreds of restriction endonucleases, the Eco R1 enzyme is the most useful and widely investigated enzyme and was isolated from E. coli RY 13" ], "exact_answer": [ "E coli" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D015246", "http://www.uniprot.org/uniprot/T2E1_ECOLX", "https://meshb.nlm.nih.gov/record/ui?ui=D015280", "https://meshb.nlm.nih.gov/record/ui?ui=D004262", "http://www.uniprot.org/uniprot/MTE1_ECOLX" ], "type": "factoid", "id": "5abd5a62fcf4565872000031", "snippets": [ { "offsetInBeginSection": 91, "offsetInEndSection": 281, "text": ". Among hundreds of restriction endonucleases, the Eco R1 enzyme is the most useful and widely investigated enzyme. After sonication and ultracentrifugation, crude extracts of E. coli RY 13 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6099579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "An endonuclease having EcoRI specificity is produced by bacteria containing the ColE1 plasmid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/349563", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 379, "text": "Such bacterial cells fail to express restriction or modification functions in vivo, and phage or plasmid DNA obtained from ColE1-containing cells has unmodified EcoRI sites that are cleaved in vitro by purified EcoRI endonuclease or by enzyme extracted from bacteria that carry ColE1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/349563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "[Characteristics of RecA-independent recombination of plasmids in E. coli cells producing restriction endonuclease EcoRI].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3025706", "endSection": "title" }, { "offsetInBeginSection": 386, "offsetInEndSection": 641, "text": " The purification of the EcoRI restriction enzyme from a strain of Escherichia coli that over-produces this enzyme was hampered by the insolubility of the protein, and hence the purification procedure was modified to optimize the recovery of active enzyme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2996987", "endSection": "abstract" } ] }, { "body": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11428412", "http://www.ncbi.nlm.nih.gov/pubmed/16034947", "http://www.ncbi.nlm.nih.gov/pubmed/19127040", "http://www.ncbi.nlm.nih.gov/pubmed/16011530", "http://www.ncbi.nlm.nih.gov/pubmed/14716388", "http://www.ncbi.nlm.nih.gov/pubmed/19009138", "http://www.ncbi.nlm.nih.gov/pubmed/8228302", "http://www.ncbi.nlm.nih.gov/pubmed/21905781" ], "ideal_answer": [ "It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis. The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. ", "It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade.", "The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis.", "It is an increasing cause of infection in immunosuppressed patients with aids in the united kingdom are known to have developed cryptococcosis. It is an increasing cause of infection in immunosuppressed patients, most notably those with hiv infection. It is an increasing cause of infection with cryptococcus neoformans has increased four-fold in the last decade. ", "The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection.", "It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis.", "The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis. " ], "exact_answer": [ "HIV infection", "HIV" ], "type": "factoid", "id": "5ace37d50340b9f058000011", "snippets": [ { "offsetInBeginSection": 548, "offsetInEndSection": 856, "text": "The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8228302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "BACKGROUND: Cryptococcal disease is an opportunistic infection that causes significant morbidity and mortality in adults with HIV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034947", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 752, "text": "Primary prophylaxis with antifungal interventions may decrease cryptococcal disease incidence and associated mortality.
OBJECTIVES: To assess the efficacy of antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV.
SEARCH STRATEGY: We searched the following databases: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, Database of Abstracts of Reviews of Effectiveness (DARE), Latin American and Caribbean Literature on the Health Sciences (LILACS), and the Cochrane Controlled Trials Register (CCTR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034947", "endSection": "abstract" }, { "offsetInBeginSection": 3028, "offsetInEndSection": 3584, "text": "When the two studies using fluconazole as the intervention were analyzed together (N=518), the incidence of cryptococcal disease was decreased in those taking fluconazole for primary prophylaxis (RR 0.25, 95% CI 0.07, 0.87) compared to those taking placebo; however, there was no significant difference in overall mortality (RR 0.59, 95% CI 0.14, 2.62).
AUTHORS' CONCLUSIONS: Antifungal primary prophylaxis with either itraconazole or fluconazole is effective in reducing the incidence of cryptococcal disease in adults with advanced HIV disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034947", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1946, "text": "Key words used include: meningitis, cryptococcal, cryptococcus, cryptococcosis, acquired immunodeficiency syndrome, human immunodeficiency virus, prophylaxis, chemoprevention, antifungal agents, and the Cochrane screen for randomized controlled trials.
SELECTION CRITERIA: Randomized controlled trials using antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV were selected.
DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034947", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 633, "text": "AIDS is the main predisposing condition for cryptococcal meningitis, and thus the profile of most patients mirrors that of HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009138", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 980, "text": "We reviewed abstracts from the following relevant conferences: International AIDS Conference, International AIDS Society Conference on HIV Pathogenesis and Treatment, and Conference on Retroviruses and Opportunistic Infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034947", "endSection": "abstract" }, { "offsetInBeginSection": 3331, "offsetInEndSection": 3522, "text": "AUTHORS' CONCLUSIONS Antifungal primary prophylaxis with either itraconazole or fluconazole is effective in reducing the incidence of cryptococcal disease in adults with advanced HIV disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "BACKGROUND Cryptococcal meningitis is a common opportunistic infection in Human Immunodeficiency Virus (HIV)-infected individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19127040", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 188, "text": "The incidence of cryptococcal meningitis has increased in parallel with that of HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14716388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus spp., is the most common form of meningitis and a leading cause of death among persons with HIV/AIDS in sub-Saharan Africa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21905781", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 414, "text": "The authors observed no differences in the radiographic appearances of pulmonary cryptococcal disease between human immunodeficiency virus (HIV) patients and other immunocompromised individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11428412", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 177, "text": "The incidence of cryptococcal meningitis has increased in parallel with that of HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14716388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Despite advances in the treatment of HIV disease, the incidence and mortality of invasive cryptococcal disease remain significant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16011530", "endSection": "abstract" } ] }, { "body": "Which genes are responsible for the high-altitude adaptation of Tibetans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26053282", "http://www.ncbi.nlm.nih.gov/pubmed/22068265", "http://www.ncbi.nlm.nih.gov/pubmed/23666208", "http://www.ncbi.nlm.nih.gov/pubmed/21030426", "http://www.ncbi.nlm.nih.gov/pubmed/24513612", "http://www.ncbi.nlm.nih.gov/pubmed/22503288", "http://www.ncbi.nlm.nih.gov/pubmed/25501874", "http://www.ncbi.nlm.nih.gov/pubmed/24654529", "http://www.ncbi.nlm.nih.gov/pubmed/28036300", "http://www.ncbi.nlm.nih.gov/pubmed/26781569", "http://www.ncbi.nlm.nih.gov/pubmed/20961960", "http://www.ncbi.nlm.nih.gov/pubmed/20466884", "http://www.ncbi.nlm.nih.gov/pubmed/20838600" ], "ideal_answer": [ "Recent studies have identified genes involved in high-altitude adaptation in Tibetans. Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. A gene (HMOX2) involved in heme catabolism, harbors potentially adaptive variants in Tibetans.", "Recent studies have identified genes involved in high-altitude adaptation in Tibetans. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions. Two functional loci in the promoter of EPAS1 gene involved in high-altitude adaptation of Tibetans.", "EGLN1 (or HIFPH2, MIM 606425) and EPAS1 (or HIF2A, MIM 603349), both related to hypoxia-inducible factor, were found most differentiated in the two regions, respectively. Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions.", "Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. " ], "exact_answer": [ [ "EGLN1", "HIFPH2" ], [ "EPAS1", "HIF2A" ], [ "PPARA" ], [ "HMOX2" ] ], "type": "list", "id": "5ace20fa0340b9f05800000c", "snippets": [ { "offsetInBeginSection": 461, "offsetInEndSection": 729, "text": "We discovered the most differentiated variants between TBN and HAN at chromosome 1q42.2 and 2p21. EGLN1 (or HIFPH2, MIM 606425) and EPAS1 (or HIF2A, MIM 603349), both related to hypoxia-inducible factor, were found most differentiated in the two regions, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20961960", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1319, "text": "All of our population genomic and statistical analyses indicate that EPAS1 and EGLN1 are most likely responsible for HAA of Tibetans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20961960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Recent studies have identified genes involved in high-altitude adaptation in Tibetans. Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503288", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 890, "text": " In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21030426", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 595, "text": "Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Identification of a Tibetan-specific mutation in the hypoxic gene EGLN1 and its contribution to high-altitude adaptation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666208", "endSection": "title" }, { "offsetInBeginSection": 322, "offsetInEndSection": 602, "text": "Here we conducted resequencing of the entire genomic region (59.4 kb) of the hypoxic gene EGLN1 (one of the top candidates from the genome-wide scans) in Tibetans and identified 185 sequence variations, including 13 novel variations (12 substitutions and 1 insertion or deletion).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666208", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1502, "text": "The estimated selective intensity (0.029 for the C allele of rs186996510) puts EGLN1 among the known genes that have undergone the strongest selection in human populations, and the onset of selection was estimated to have started at the early Neolithic (\u223c8,400 years ago). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Two functional loci in the promoter of EPAS1 gene involved in high-altitude adaptation of Tibetans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501874", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "EPAS1 involves in the hypoxic response and is suggested to be responsible for the genetic adaptation of high-altitude hypoxia in Tibetans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501874", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 626, "text": "Three of these genes (EPAS1, EGLN1 and PPARA) are associated with decreased haemoglobin levels compared with non-Tibetans living at altitude. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26053282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "HMOX2 Functions as a Modifier Gene for High-Altitude Adaptation in Tibetans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26781569", "endSection": "title" }, { "offsetInBeginSection": 352, "offsetInEndSection": 489, "text": "In this study, we report a downstream gene (HMOX2) involved in heme catabolism, which harbors potentially adaptive variants in Tibetans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26781569", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1409, "text": "Collectively, we propose that HMOX2 contributes to high-altitude adaptation in Tibetans by functioning as a modifier in the regulation of hemoglobin metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26781569", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 618, "text": "Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20466884", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 325, "text": "Studies of Tibetans revealed candidates for high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower haemoglobin concentration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24513612", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 756, "text": "Here we analyse genotype data for the Nepalese Sherpa, and find that Tibetans are a mixture of ancestral populations related to the Sherpa and Han Chinese. EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24513612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24654529", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1531, "text": "Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20838600", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 729, "text": "(or HIFPH2, MIM 606425) and EPAS1 (or HIF2A, MIM 603349), both related to hypoxia-inducible factor, were found most differentiated in the two regions, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20961960", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 720, "text": "It demonstrated that the C allele of rs56721780:G C decreased the binding of IKZF1, leading to the attenuated transcriptional repression of EPAS1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501874", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 756, "text": "EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24513612", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 370, "text": "Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22503288", "endSection": "abstract" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1444, "text": "All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24654529", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 707, "text": "The Tibetan-specific 200 kb EPAS1 haplotype introgressed from an archaic human population related to Denisovans which underwent evolutionary decay; however, the functional variant(s) responsible for high-altitude adaptation at EPAS1/HIF-2\u03b1 have not yet been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28036300", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 1041, "text": "Further functional analysis revealed that lysyl oxidase (LOX) gene, which was reported to be responsible for extracellular matrix protein cross-linking of amnion previously, was a direct target of EPAS1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Two functional loci in the promoter of EPAS1 gene involved in high-altitude adaptation of Tibetans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501874", "endSection": "title" } ] }, { "body": "Which is the main protein in brown adipose tissue (BAT) active in thermogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28794154", "http://www.ncbi.nlm.nih.gov/pubmed/26304220", "http://www.ncbi.nlm.nih.gov/pubmed/28453364", "http://www.ncbi.nlm.nih.gov/pubmed/28057582", "http://www.ncbi.nlm.nih.gov/pubmed/26515423", "http://www.ncbi.nlm.nih.gov/pubmed/26518386" ], "ideal_answer": [ "Uncoupling protein 1 (UCP1) is the hallmark protein responsible for cold- and diet-induced thermogenesis in brown adipose tissue (BAT)." ], "exact_answer": [ "Uncoupling protein 1", "UCP1" ], "type": "factoid", "id": "5a8980d2fcd1d6a10c00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "Brown adipose tissue (BAT) mitochondria are distinct from their counterparts in other tissues in that ATP production is not their primary physiologic role. BAT mitochondria are equipped with a specialized protein known as uncoupling protein 1 (UCP1). UCP1 short-circuits the electron transport chain, allowing mitochondrial membrane potential to be transduced to heat, making BAT a tissue capable of altering energy expenditure and fuel metabolism in mammals without increasing physical activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Uncoupling protein 1 (UCP1) is the hallmark protein responsible for cold- and diet-induced thermogenesis in brown adipose tissue (BAT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28057582", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) (i.e.uncoupling protein 1 (UCP1)-based)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28794154", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 197, "text": "UCP1's central role in non-shivering thermogenesis is acknowledged", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26518386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "JAK2 promotes brown adipose tissue function and is required for diet- and cold-induced thermogenesis in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515423", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Brown adipocytes (BAs) are specialized for adaptive thermogenesis and, upon sympathetic stimulation, activate mitochondrial uncoupling protein (UCP)-1 and oxidize fatty acids to generate heat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26304220", "endSection": "abstract" } ] }, { "body": "Which method is Proseek based on?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29026368", "http://www.ncbi.nlm.nih.gov/pubmed/29050213" ], "ideal_answer": [ "proximity extension immunoassay" ], "exact_answer": [ "proximity extension immunoassay", "PEA" ], "type": "factoid", "id": "5a9e202bde7cb99d40000002", "snippets": [ { "offsetInBeginSection": 423, "offsetInEndSection": 652, "text": "We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n\u00a0=\u00a075) and age-matched healthy control subjects (n\u00a0=\u00a023).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29026368", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 247, "text": "Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29050213", "endSection": "abstract" } ] }, { "body": "With which personality traits has the human monoamine oxidase A (MAOA) gene been associated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17347351", "http://www.ncbi.nlm.nih.gov/pubmed/10943908", "http://www.ncbi.nlm.nih.gov/pubmed/16436187", "http://www.ncbi.nlm.nih.gov/pubmed/25497297", "http://www.ncbi.nlm.nih.gov/pubmed/15652876", "http://www.ncbi.nlm.nih.gov/pubmed/29073746", "http://www.ncbi.nlm.nih.gov/pubmed/28851912", "http://www.ncbi.nlm.nih.gov/pubmed/15870836", "http://www.ncbi.nlm.nih.gov/pubmed/26494873", "http://www.ncbi.nlm.nih.gov/pubmed/20810002", "http://www.ncbi.nlm.nih.gov/pubmed/25698585", "http://www.ncbi.nlm.nih.gov/pubmed/14697883", "http://www.ncbi.nlm.nih.gov/pubmed/12554604", "http://www.ncbi.nlm.nih.gov/pubmed/26851573", "http://www.ncbi.nlm.nih.gov/pubmed/19194374", "http://www.ncbi.nlm.nih.gov/pubmed/21554924", "http://www.ncbi.nlm.nih.gov/pubmed/17417058", "http://www.ncbi.nlm.nih.gov/pubmed/25794322" ], "ideal_answer": [ "Association studies suggest that the low activity variant of the monoamine oxidase A (MAOA)-uVNTR polymorphism confers risk for emotional disturbances associated with antisocial traits, particularly in males. These include antisocial and borderline personality disorders and antisocial aggression.", "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits. The interaction of the low activity variant of the monoamine oxidase-A (MAOA-L) gene and early childhood adversity has been shown to predict aggression in clinical and non-clinical populations Monoamine Oxidase-A Genetic Variants and Childhood Abuse Predict Impulsiveness in Borderline Personality Disorder.", "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits. ", "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits. Monoamine oxidase a gene is associated with borderline personality disorder. Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder.", "Monoamine oxidase A (MAOA) gene has an important role in the regulation of neurotransmitter levels and a large number of human behaviors. For example, it has been shown that childhood maltreatment interacts with a monoamine oxidase A (MAOA) gene variant to predict antisocial behavior that is often associated with alcoholism, and an interaction between early life stress and a serotonin transporter promoter variant predicts alcohol abuse in nonhuman primates and depression in humans. The purpose of the present study was to examine whether a cumulative genetic score (CGS) containing the monoamine oxidase A (MAOA) and the human serotonin transporter gene linked polymorphism (5-HTTLPR) was associated with IPV perpetration after accounting for the effects of alcohol problems, drug problems, age, and length of relationship. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences.", "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits." ], "exact_answer": [ [ "antisocial personality disorder" ], [ "borderline personality disorder" ], [ "antisocial aggression" ] ], "type": "list", "id": "5a99566e1d1251d03b00000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28851912", "endSection": "title" }, { "offsetInBeginSection": 196, "offsetInEndSection": 388, "text": "The interaction of the low activity variant of the monoamine oxidase-A (MAOA-L) gene and early childhood adversity has been shown to predict aggression in clinical and non-clinical populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29073746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Monoamine Oxidase-A Genetic Variants and Childhood Abuse Predict Impulsiveness in Borderline Personality Disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29073746", "endSection": "title" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1460, "text": " These preliminary results suggest that MAOA-L may modulate the impact of childhood abuse on impulsivity in BPD. Results additionally indicate that impulsiveness may be expressed differently in BPD and ASPD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29073746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Elevated Monoamine Oxidase-A Distribution Volume in Borderline Personality Disorder Is Associated With Severity Across Mood Symptoms, Suicidality, and Cognition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25698585", "endSection": "title" }, { "offsetInBeginSection": 1457, "offsetInEndSection": 1646, "text": "These results suggest that elevated MAO-A VT is associated with multiple indicators of BPD severity, including BPD symptomatology, mood symptoms, suicidality, and neurocognitive impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25698585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "No association between a polymorphism in the promoter region of the MAOA gene with antisocial personality traits in alcoholics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12554604", "endSection": "title" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1313, "text": "Taken together, these findings suggest that the three-repeat allele of the MAOAuVNTR 30-bp polymorphism is not associated with impulsive and aggressive personality traits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12554604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Different allele distribution of a regulatory MAOA gene promoter polymorphism in antisocial and anxious-depressive alcoholics", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10943908", "endSection": "title" }, { "offsetInBeginSection": 109, "offsetInEndSection": 320, "text": "The present study tested whether a novel functional polymorphism in the promotor region of the X-chromosomal monoamine oxidase A gene (MAOA) was related to antisocial and anxious-depressive traits in alcoholics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10943908", "endSection": "abstract" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1074, "text": "aken together, these findings suggest that the 3-repeat allele of the MAOA polymorphism contributes modestly to the dimension of overand underreactive behaviors as possible antecedents of alcoholism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10943908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Association studies suggest that the low activity variant of the monoamine oxidase A (MAOA)-uVNTR polymorphism confers risk for emotional disturbances associated with antisocial traits, particularly in males. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19194374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "A polymorphism of the MAOA gene is associated with emotional brain markers and personality traits on an antisocial index", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19194374", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 126, "text": "The monoamine oxidase A (MAOA) gene has been shown to moderate the impact of maltreatment on antisocial behaviour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26494873", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 941, "text": "Non-linear interactions between the MAOA gene and violence were detected, suggesting that the genetic moderation may come about once a certain level of violence is experienced", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26494873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The history of research on the association between platelet monoamine oxidase (MAO) activity and personality traits, such as sensation seeking and impulsiveness, is reviewed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14697883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Monoamine oxidase a gene is associated with borderline personality disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17417058", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 319, "text": "As for its role in aggression, impulsivity, suicide and mood liability, monoamine oxidase A can be considered a functional candidate in borderline personality disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17417058", "endSection": "abstract" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1123, "text": "These results show that the monoamine oxidase A gene may play an important role in the etiological development of the borderline personality disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17417058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554924", "endSection": "title" }, { "offsetInBeginSection": 318, "offsetInEndSection": 422, "text": "However, clinical associations between this VNTR genotype and behavioral states have been inconsistent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21554924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Monoamine oxidase A gene promoter methylation and transcriptional downregulation in an offender population with antisocial personality disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25497297", "endSection": "title" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1419, "text": "hese results are consistent with prior literature suggesting MAOA and serotonergic dysregulation in antisocial populations. Our results offer the first evidence suggesting epigenetic mechanisms may contribute to MAOA dysregulation in antisocial offenders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25497297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "For example, it has been shown that childhood maltreatment interacts with a monoamine oxidase A (MAOA) gene variant to predict antisocial behavior that is often associated with alcoholism, and an interaction between early life stress and a serotonin transporter promoter variant predicts alcohol abuse in nonhuman primates and depression in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17347351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15652876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 377, "text": "By conferring allele-specific transcriptional activity on the monoamine oxidase A (MAOA) gene in humans, length variation of a repetitive sequence [(variable number of tandem repeat (VNTR)] in the MAOA promoter influences a constellation of personality traits related to aggressive and antisocial behavior and increases the risk of neurodevelopmental and psychiatric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16436187", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 244, "text": "Genotypes with three-repeat alleles were reported to be associated with antisocial as well as impulsive traits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12554604", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 641, "text": "Platelet MAO-B activity has been associated with psychopathy- and aggression-related personality traits, while variants of the MAOA and MAOB genes have been associated with diverse clinical phenotypes, including aggressiveness, antisocial problems and violent delinquency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26851573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Association studies suggest that the low activity variant of the monoamine oxidase A (MAOA)-uVNTR polymorphism confers risk for emotional disturbances associated with antisocial traits, particularly in males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19194374", "endSection": "abstract" }, { "offsetInBeginSection": 1428, "offsetInEndSection": 1598, "text": "CONCLUSION Taken together, these findings suggest that the MAOA-L genotype is to some extent associated with impulsive and antisocial personality traits in alcoholic men.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Relationship of monoamine oxidase A binding to adaptive and maladaptive personality traits.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20810002", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15870836", "endSection": "title" } ] }, { "body": "What is the function of HDAC proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17767915", "http://www.ncbi.nlm.nih.gov/pubmed/10220385", "http://www.ncbi.nlm.nih.gov/pubmed/23724067", "http://www.ncbi.nlm.nih.gov/pubmed/26927903", "http://www.ncbi.nlm.nih.gov/pubmed/27345839", "http://www.ncbi.nlm.nih.gov/pubmed/10869435", "http://www.ncbi.nlm.nih.gov/pubmed/11602581", "http://www.ncbi.nlm.nih.gov/pubmed/28930559", "http://www.ncbi.nlm.nih.gov/pubmed/17227860", "http://www.ncbi.nlm.nih.gov/pubmed/27668865", "http://www.ncbi.nlm.nih.gov/pubmed/15050820", "http://www.ncbi.nlm.nih.gov/pubmed/23088873", "http://www.ncbi.nlm.nih.gov/pubmed/22621256", "http://www.ncbi.nlm.nih.gov/pubmed/19443688", "http://www.ncbi.nlm.nih.gov/pubmed/27939885", "http://www.ncbi.nlm.nih.gov/pubmed/28078999" ], "ideal_answer": [ "Histone deacetylases influence diverse cellular processes and may contribute to tumor development and progression by multiple mechanisms. Histone deacetylases prevent the relaxation of chromatin, and positively or negatively regulate transcription. ", "Histone deacetylases (HDACs) prevent the relaxation of chromatin, and positively or negatively regulate transcription and thus cellular processes" ], "exact_answer": [ "HDACs regulate chromatin structure and gene expression" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D006655", "http://amigo.geneontology.org/amigo/term/GO:0000118" ], "type": "factoid", "id": "5aafc37afcf4565872000010", "snippets": [ { "offsetInBeginSection": 107, "offsetInEndSection": 226, "text": "Histone deacetylases (HDACs) prevent the relaxation of chromatin, and positively or negatively regulate transcription. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28930559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Histone deacetylases (HDACs) influence diverse cellular processes and may contribute to tumor development and progression by multiple mechanisms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28078999", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 402, "text": "Accumulating evidence has implicated histone deacetylase (HDAC) proteins in cell specification, proliferation, and differentiation in diverse embryonic and adult tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27668865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The function of eukaryotic histone deacetylase (HDAC) has been extensively studied for its critical role in transcriptional regulation and carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17767915", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Histone deacetylases (HDACs) are key regulators of gene expression that require assembly into larger protein complexes for activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17227860", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 393, "text": "Histone deacetylase (HDAC) proteins have a major role in epigenetic regulation of chromatin structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927903", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 286, "text": "HDAC is a family of enzymes involved in deacetylation of lysine residues on histone and non-histone proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22621256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Gene expression is in part controlled by chromatin remodeling factors and the acetylation state of nucleosomal histones. The latter process is regulated by histone acetyltransferases and histone deacetylases (HDACs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10220385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Class I histone deacetylases (HDACs) are known to remove acetyl groups from histone tails. This liberates positive charges on the histone tail and allows for tighter winding of DNA, preventing transcription factor binding and gene activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27345839", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 434, "text": "Histone deacetylases (HDACs) and histone acetyl transferases catalyze the reversible acetylation of histones and nonhistone substrates to control the epigenetic and transcriptomic landscape of normal and tumor cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23088873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Histone deacetylases (HDACs) modify core histones and participate in large regulatory complexes that both suppress and enhance transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15050820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Transcription is controlled in part by the dynamic acetylation and deacetylation of histone proteins. The latter process is mediated by histone deacetylases (HDACs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10869435", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 398, "text": "Specifically, the histone deacetylase (HDAC) family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724067", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 277, "text": "Specifically, histone deacetylase (HDAC) proteins repress transcription by deacetylating histones. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11602581", "endSection": "abstract" } ] }, { "body": "What is the H4S47C cleavage mapping method used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24737863", "http://www.ncbi.nlm.nih.gov/pubmed/26275423", "http://www.ncbi.nlm.nih.gov/pubmed/25491770" ], "ideal_answer": [ "To identify nucleosomes with alternative structures genome-wide, we used H4S47C-anchored cleavage mapping, which revealed that 5% of budding yeast (Saccharomyces cerevisiae) nucleosome positions have asymmetric histone-DNA interactions. To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing. To resolve this controversy, we have applied H4S47C-anchored cleavage mapping, which reveals the precise position of histone H4 in every nucleosome in the genome.", "H4S47C-anchored cleavage mapping reveals the precise position of histone H4 in every nucleosome in the genome.", " To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing. To resolve this controversy, we have applied H4S47C-anchored cleavage mapping, which reveals the precise position of histone H4 in every nucleosome in the genome.", "To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing. ", "To identify nucleosomes with alternative structures genome-wide, we used H4S47C-anchored cleavage mapping, which revealed that 5% of budding yeast (Saccharomyces cerevisiae) nucleosome positions have asymmetric histone-DNA interactions.", "To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing." ], "exact_answer": [ "nucleosome positioning", "H4 position" ], "type": "factoid", "id": "5a885add61bb38fb24000017", "snippets": [ { "offsetInBeginSection": 113, "offsetInEndSection": 349, "text": "To identify nucleosomes with alternative structures genome-wide, we used H4S47C-anchored cleavage mapping, which revealed that 5% of budding yeast (Saccharomyces cerevisiae) nucleosome positions have asymmetric histone-DNA interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25491770", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 708, "text": "Micrococcal nuclease (MNase) sequence-based profiles of asymmetric nucleosome positions revealed a corresponding asymmetry in MNase protection near the dyad axis, suggesting that the loss of DNA contacts around H4S47 is accompanied by protection of the DNA from MNase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25491770", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 332, "text": "To resolve this controversy, we have applied H4S47C-anchored cleavage mapping, which reveals the precise position of histone H4 in every nucleosome in the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737863", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 327, "text": " To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275423", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 516, "text": "We find that cleavage patterns at centromeres are unique within the genome and are incompatible with symmetrical structures, including octameric nucleosomes and (Cse4/H4)2 tetrasomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737863", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 759, "text": "Centromere cleavage patterns are compatible with a precisely positioned core structure, one in which each of the 16 yeast centromeres is occupied by oppositely oriented Cse4/H4/H2A/H2B hemisomes in two rotational phases within the population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737863", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 569, "text": "H3 nucleosomes are nearly absent from the central domain, which is occupied by centromere-specific H3 (cenH3 or CENP-A) nucleosomes with two H4s per particle that are mostly unpositioned and are more widely spaced than nucleosomes elsewhere.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26275423", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 334, "text": "To resolve this controversy, we have applied H4S47C-anchored cleavage mapping, which reveals the precise position of histone H4 in every nucleosome in the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737863", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 761, "text": "Centromere cleavage patterns are compatible with a precisely positioned core structure, one in which each of the 16 yeast centromeres is occupied by oppositely oriented Cse4/H4/H2A/H2B hemisomes in two rotational phases within the population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737863", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 518, "text": "We find that cleavage patterns at centromeres are unique within the genome and are incompatible with symmetrical structures, including octameric nucleosomes and (Cse4/H4)2 tetrasomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737863", "endSection": "abstract" } ] }, { "body": "Which human gene encode for DNA polymerase \u03b8?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27264557", "http://www.ncbi.nlm.nih.gov/pubmed/28668117" ], "ideal_answer": [ "DNA polymerase theta (pol \u03b8) is an evolutionarily conserved protein encoded by the POLQ gene in mammalian genomes" ], "exact_answer": [ "DNA polymerase theta (pol \u03b8) is an evolutionarily conserved protein encoded by the POLQ gene in mammalian genomes" ], "type": "factoid", "id": "5aacd487fcf4565872000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "DNA polymerase theta (pol \u03b8) is an evolutionarily conserved protein encoded by the POLQ gene in mammalian genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28668117", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "DNA polymerase theta (pol \u03b8) is encoded in the genomes of many eukaryotes, though not in fungi. Pol \u03b8 is encoded by the POLQ gene in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27264557", "endSection": "abstract" } ] }, { "body": "In what percentage of skeletal muscle fibers is dystrophin expression restored after PPMO- mediated exon skipping?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24942628" ], "ideal_answer": [ "PPMO-mediated exon skipping restored the dystrophin expression in nearly 100% skeletal muscle fibers in all age groups." ], "exact_answer": [ "100%" ], "type": "factoid", "id": "5ac0a82d19833b0d7b000003", "snippets": [ { "offsetInBeginSection": 702, "offsetInEndSection": 1109, "text": "Biweekly intravenous (i.v.) administration of the PPMO restored the dystrophin expression in nearly 100% skeletal muscle fibers in all age groups. This was associated with the restoration of dystrophin-associated proteins including functional glycosylated dystroglycan and neuronal nitric synthase. However, therapeutic outcomes clearly depended on severity of the disease at the time the treatment started.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24942628", "endSection": "abstract" } ] }, { "body": "Which miRNA is associated with the circular RNA ciRS-7?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28253710" ], "ideal_answer": [ "circular RNA-7 (ciRS-7) acts as a sponge of miR-7 and thus inhibits its activity." ], "exact_answer": [ "miR-7" ], "type": "factoid", "id": "5ac725250340b9f058000006", "snippets": [ { "offsetInBeginSection": 390, "offsetInEndSection": 975, "text": "In addition, according to recent studies, circular RNA-7 (ciRS-7) acts as a sponge of miR-7 and thus inhibits its activity. Numerous evidences have confirmed expression of miR-7 is dysregulated in cancer tissues, however, whether ciRS-7 invovled in oncogenesis by acting as sponge of miR-7 remains unclear. Most recently, a study reported ciRS-7 acted as an oncogene in hepatocellular carcinoma through targeting miR-7 expression. This suggest ciRS-7/ miR-7 axis affects oncogenesis, and it provides a new perspective on the mechanisms of decreased miR-7 expression in cancer tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253710", "endSection": "abstract" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1400, "text": "This review summarizes the structure and function of circRNAs and provides evidence for the impact of ciRS-7 in promoting the development of cancer by acting as sponge of miR-7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28253710", "endSection": "abstract" } ] }, { "body": "Which are the two main bacterial phyla in human gut?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28293225", "http://www.ncbi.nlm.nih.gov/pubmed/27900395" ], "ideal_answer": [ "Out of thousands of bacterial species-level phylotypes inhabiting the human gut, the majority belong to two dominant phyla, the Bacteroidetes and Firmicutes" ], "exact_answer": [ "Bacteroidetes and Firmicutes" ], "type": "factoid", "id": "5abd2ce0fcf456587200002a", "snippets": [ { "offsetInBeginSection": 147, "offsetInEndSection": 303, "text": "Out of thousands of bacterial species-level phylotypes inhabiting the human gut, the majority belong to two dominant phyla, the Bacteroidetes and Firmicutes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27900395", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 366, "text": "the prevalence of some representative viable bacteria from the four dominant phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293225", "endSection": "abstract" } ] }, { "body": "What are 7 symptoms of yellow fever?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20439976", "http://www.ncbi.nlm.nih.gov/pubmed/24056028", "http://www.ncbi.nlm.nih.gov/pubmed/28810279", "http://www.ncbi.nlm.nih.gov/pubmed/25412185" ], "ideal_answer": [ "Yellow fever is considered to be a hemorrhagic fever and illness is characterized by fever, headache, myalgia, gastrointestinal symptoms, hepatic and renal dysfunction, multi-organ failure, shock and coagulopathy." ], "exact_answer": [ [ "fever" ], [ "multi organ failure" ], [ "hemorrhage" ], [ "headache" ], [ "myalgia" ], [ "hepatic dysfunction" ], [ "renal dysfunction" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D015004", "http://www.disease-ontology.org/api/metadata/DOID:9682" ], "type": "list", "id": "5aac5469fcf4565872000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25412185", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1043, "text": ". YF usually causes fever, muscle pain with prominent backache, headache, shivers, loss of appetite, and nausea or vomiting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056028", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 617, "text": "The illness was characterized by fever, headache, myalgia, gastrointestinal symptoms, hepatic and renal dysfunction, and (in the fatal case), shock and coagulopathy,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20439976", "endSection": "abstract" } ] }, { "body": "Which test is used for the definition of colour-blindness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23267377", "http://www.ncbi.nlm.nih.gov/pubmed/2378506", "http://www.ncbi.nlm.nih.gov/pubmed/7819984", "http://www.ncbi.nlm.nih.gov/pubmed/6600702", "http://www.ncbi.nlm.nih.gov/pubmed/21137654" ], "ideal_answer": [ "Color-blindness problems are detected by the Ishihara Test.", "12 patients had color blindness based on the Ishihara test", "12 patients had color blindness based on the Ishihara test. " ], "exact_answer": [ "Ishihara test", "Ishihara" ], "type": "factoid", "id": "5ad6e431133db5eb7800000e", "snippets": [ { "offsetInBeginSection": 1106, "offsetInEndSection": 1164, "text": "12 patients had color blindness based on the Ishihara test", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23267377", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 162, "text": "Basque students (174 males and 218 females), using the Ishihara test cards (1987).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2378506", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 534, "text": "The results obtained from male individuals by 919 Ishihara-tests were only considered, categorized and graphically represented according to their age groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6600702", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 740, "text": "A cross-sectional descriptive and analytical study was conducted among 633 TUMS Clinical Laboratory Sciences' Students and Hospitals' Clinical Laboratories' Employees to detect color-blindness problems by Ishihara Test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21137654", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 292, "text": "Results of Isihara colour blindness tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7819984", "endSection": "abstract" } ] }, { "body": "Of what origin is the MCF-7 cell line?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29055574", "http://www.ncbi.nlm.nih.gov/pubmed/25792283", "http://www.ncbi.nlm.nih.gov/pubmed/26877254", "http://www.ncbi.nlm.nih.gov/pubmed/28358602" ], "ideal_answer": [ "MCF7 is an ER+ breast cancer cell line." ], "exact_answer": [ "MCF7 is an ER+ breast cancer cell line" ], "type": "factoid", "id": "5ac08fe7d0c506ce46000003", "snippets": [ { "offsetInBeginSection": 866, "offsetInEndSection": 905, "text": " an ER+ breast cancer cell line (MCF-7)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26877254", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 891, "text": " Two different types of tumor cells, MCF-7 and MDA-MB-231, both from the same origin of breast carcinoma cells, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29055574", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 629, "text": "MCF7, and PC3 adenocarcinoma cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28358602", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 589, "text": "MCF7, Hs578t and MDA-MB-231 breast cancer cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25792283", "endSection": "abstract" } ] }, { "body": "Is lumican a secreted protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17050378", "http://www.ncbi.nlm.nih.gov/pubmed/22814255", "http://www.ncbi.nlm.nih.gov/pubmed/27126993", "http://www.ncbi.nlm.nih.gov/pubmed/22266188", "http://www.ncbi.nlm.nih.gov/pubmed/26351669" ], "ideal_answer": [ "Yes, Lumican is a secreted proteoglycan that regulates collagen fibril assembly." ], "exact_answer": "yes", "type": "yesno", "id": "5ad255210340b9f058000018", "snippets": [ { "offsetInBeginSection": 296, "offsetInEndSection": 442, "text": "fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-\u03b1 secrete the small leucine-rich proteoglycan lumican", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26351669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "TNF-\u03b1-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26351669", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Secreted 70kDa lumican stimulates growth and inhibits invasion of human pancreatic cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266188", "endSection": "title" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1359, "text": "the elevated level of lumican secretion to extracellular space leads to actin cytoskeletal remodeling followed by an increase in migration capacity of human colon LS180 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22814255", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 450, "text": "Lumican is a secreted proteoglycan that regulates collagen fibril assembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27126993", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1180, "text": "This is the first time that the synthesis and secretion of lumican in human melanoma cell lines is reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17050378", "endSection": "abstract" } ] }, { "body": "Cytochrome p450 CYP3A is induced by rifampicin and compounds used to treat what virus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16432264", "http://www.ncbi.nlm.nih.gov/pubmed/20834094" ], "ideal_answer": [ "Etravirine is an effective and well-tolerated recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV type-1-infected patients with previous antiretroviral treatment experience. Etravirine is a weak inducer of cytochrome P450 (CYP)3A", "Four CYP3A inducers were used: rifampicin, rifabutin, carbamazepine, and efavirenz Etravirine is an effective and well-tolerated recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV type-1-infected patients with previous antiretroviral treatment experience." ], "exact_answer": [ "HIV" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D014780" ], "type": "factoid", "id": "5ab2cc66fcf4565872000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 451, "text": "Etravirine is an effective and well-tolerated recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV type-1-infected patients with previous antiretroviral treatment experience. Considering the importance of combining antiretrovirals for their optimal use in treating HIV, a number of drug-drug interactions with etravirine and other antiretrovirals have been evaluated. Etravirine is a weak inducer of cytochrome P450 (CYP)3A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20834094", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 643, "text": "oreover, medications prescribed to HIV-positive patients may also be CYP3A inhibitors and inducers: Tipranavir, in the absence of ritonavir, is a CYP3A inducer, and ritonavir is a CYP3A inhibitor. F", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16432264", "endSection": "abstract" } ] }, { "body": "Which human chromosome is the product of fusion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15815621", "http://www.ncbi.nlm.nih.gov/pubmed/27423248", "http://www.ncbi.nlm.nih.gov/pubmed/22419167", "http://www.ncbi.nlm.nih.gov/pubmed/28333343", "http://www.ncbi.nlm.nih.gov/pubmed/11435402", "http://www.ncbi.nlm.nih.gov/pubmed/1924367", "http://www.ncbi.nlm.nih.gov/pubmed/11196135" ], "ideal_answer": [ "The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2. We propose a model where an ancestral human-chimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. ", "The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2.", "Origin of human chromosome 2: an ancestral telomere-telomere fusion.", "Human chromosome 2 originated from the fusion of two ancestral primate chromosomes.", "Origin of human chromosome 2: an ancestral telomere-telomere fusion. It is known that human chromosome 2 originated from the fusion of two ancestral primate chromosomes. ", "The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2. " ], "exact_answer": [ "chromosome 2", "2" ], "type": "factoid", "id": "5ace238e0340b9f05800000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419167", "endSection": "title" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1121, "text": "We propose a model where an ancestral human-chimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22419167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "It is known that human chromosome 2 originated from the fusion of two ancestral primate chromosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11196135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Origin of human chromosome 2: an ancestral telomere-telomere fusion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1924367", "endSection": "title" }, { "offsetInBeginSection": 586, "offsetInEndSection": 797, "text": "We conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1924367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Human chromosome 2 is a product of a telomere fusion of two ancestral chromosomes and loss/degeneration of one of the two original centromeres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27423248", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 961, "text": "We investigate the most recent product of a chromosome fusion event fixed in the human lineage, human chromosome 2, whose stability was acquired by the suppression of one centromere, resulting in a unique difference in chromosome number between humans (46 chromosomes) and our most closely related ape relatives (48 chromosomes).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28333343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15815621", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1243, "text": "By doing so, one is able to provide evidence for the presence of both active and degenerate centromeric satellite profiles on chromosome 2 in these archaic genomes, supporting the hypothesis that the chromosomal fusion event took place prior to our last common ancestor with Denisovan and Neandertal hominins and presenting a genomic reference for predicting karyotype in ancient genomic datasets.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27423248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Centromere Destiny in Dicentric Chromosomes: New Insights from the Evolution of Human Chromosome 2 Ancestral Centromeric Region.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28333343", "endSection": "title" }, { "offsetInBeginSection": 435, "offsetInEndSection": 706, "text": "Human chromosome 2 arose as a result of a telomeric fusion between acrocentric chromosomes, whereas chromosomes 4 and 19 in Gorilla gorilla are the products of a reciprocal translocation between ancestral chromosomes, syntenic to human chromosomes 5 and 17, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11435402", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1664, "text": "Our results suggest two possible centromere inactivation models to explain the evolutionarily stabilization of human chromosome 2 over the last 5-6 million years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28333343", "endSection": "abstract" } ] }, { "body": "Where is the EpCam protein mainly located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23486470", "http://www.ncbi.nlm.nih.gov/pubmed/25477371", "http://www.ncbi.nlm.nih.gov/pubmed/26268754", "http://www.ncbi.nlm.nih.gov/pubmed/28327103", "http://www.ncbi.nlm.nih.gov/pubmed/26493939", "http://www.ncbi.nlm.nih.gov/pubmed/25960617" ], "ideal_answer": [ "Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein" ], "exact_answer": [ "transmembrane expression" ], "type": "factoid", "id": "5ac09a7b19833b0d7b000001", "snippets": [ { "offsetInBeginSection": 954, "offsetInEndSection": 1216, "text": "The following cell-surface markers were immunohistochemically analyzed: E-cadherin, epithelial membrane antigen (EMA), human epidermal growth receptor type 2 (Her2/neu), carcinoembryonic antigen (CEA), \u03b1v\u03b26 integrin and epithelial cell adhesion molecule (EpCAM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28327103", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1033, "text": "Tumor cells display increased EpCAM expression that often correlates with the loss of strict basolateral localization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493939", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1728, "text": "Papillary thyroid carcinoma shows loss of EpCAM membranous expression and increased cytoplasmic/nuclear accumulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26268754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Epithelial cell adhesion molecule (EpCAM) (CD326) is a surface glycoprotein expressed by invasive carcinomas and some epithelia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23486470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein, which is frequently and highly expressed on carcinomas, tumor-initiating cells, selected tissue progenitors, and embryonic and adult stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25477371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein overexpressed in human epithelioma but with relatively low expression in normal epithelial tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25960617", "endSection": "abstract" } ] }, { "body": "What is the drug target for Eliquis (Apixaban)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27653758", "http://www.ncbi.nlm.nih.gov/pubmed/26095540", "http://www.ncbi.nlm.nih.gov/pubmed/24624626", "http://www.ncbi.nlm.nih.gov/pubmed/26369819", "http://www.ncbi.nlm.nih.gov/pubmed/25322783", "http://www.ncbi.nlm.nih.gov/pubmed/28439702", "http://www.ncbi.nlm.nih.gov/pubmed/23649961", "http://www.ncbi.nlm.nih.gov/pubmed/23677804", "http://www.ncbi.nlm.nih.gov/pubmed/24711240", "http://www.ncbi.nlm.nih.gov/pubmed/23535530", "http://www.ncbi.nlm.nih.gov/pubmed/21985171" ], "ideal_answer": [ "The new oral anticoagulants (NOAC) Apixaban (Eliquis) is a direct anti-Xa inhibitors" ], "exact_answer": [ "factor Xa" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D065427", "http://www.biosemantics.org/jochem#4243936" ], "type": "factoid", "id": "5abbe429fcf456587200001c", "snippets": [ { "offsetInBeginSection": 245, "offsetInEndSection": 457, "text": "The new oral anticoagulants (NOAC) include dabigatran etexilate (Pradaxa\u00ae), a direct thrombin inhibitor, and rivaroxaban (Xarelto\u00ae), Apixaban (Eliquis) and Edoxaban (Lixiana\u00ae), which are direct anti-Xa inhibitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23649961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "The new direct oral anticoagulants directly targeting thrombin (factor IIa) or factor-Xa, are currently used for the treatment of deep venous thrombosis and pulmonary embolism (rivaroxaban, Xarelto) or for the prevention of systemic embolism in non-valvular atrial fibrillation (rivaroxaban; dabigatran, Pradaxa; Apixaban, Eliquis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24624626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Apixaban (Eliquis), rivaroxaban (Xarelto), and edoxaban (Savaysa) are the new Xa inhibitors that have been recently approved by the U.S. FDA and are in current clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26369819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The direct factor Xa inhibitor apixaban (Eliquis(\u00ae)) has predictable pharmacodynamics and pharmacokinetics and does not require routine anticoagulation monitoring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23677804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The new oral anticoagulants (NOAC) include dabigatran etexilate (Pradaxa\u00ae), a direct thrombin inhibitor, and rivaroxaban (Xarelto\u00ae), Apixaban (Eliquis) and Edoxaban (Lixiana\u00ae), which are direct anti-Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23649961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND: apixaban (BMS-562247) (Eliquis(\u00ae)) is a novel, orally active, selective, direct, reversible inhibitor of the coagulation factor Xa (FXa).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25322783", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 482, "text": "They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto, Bayer HealthCare), apixaban (Eliquis, Bristol-Myers Squibb), and edoxaban (Lixiana/Savaysa, Daiichi-Sankyo).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095540", "endSection": "abstract" }, { "offsetInBeginSection": 1764, "offsetInEndSection": 1942, "text": "Apixaban (Eliquis), rivaroxaban (Xarelto), and edoxaban (Savaysa) are the new Xa inhibitors that have been recently approved by the U.S. FDA and are in current clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26369819", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 620, "text": "Apixaban is the second oral direct selective factor Xa inhibitor approved for the prevention of stroke/systemic embolism in patients with nonvalvular AF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23535530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Apixaban (Eliquis\u2122), an oral direct factor Xa inhibitor, is being developed by Bristol-Myers Squibb and Pfizer as a therapy for the prevention and/or treatment of thrombotic disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21985171", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 423, "text": "These specific substances directly block either thrombin (e.g., dabigatran etexilate) or Factor Xa (e.g., apixaban).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28439702", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1301, "text": "Due to the high protein binding the direkt FXa-inhibitors rivaroxaban (Xarelto\u00ae) and apixaban (Eliquis\u00ae) can not be hemodialysed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24711240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Apixaban (Eliquis\u00ae) is an oral, direct factor Xa inhibitor that is available for use in the treatment and secondary prevention of venous thromboembolism (VTE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27653758", "endSection": "abstract" } ] }, { "body": "What in vivo tau tracers are being used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26572762", "http://www.ncbi.nlm.nih.gov/pubmed/27334944" ], "ideal_answer": [ "in-vivo tau PET imaging ligands include [(18)F]THK523, [(18)F]THK5117, [(18)F]THK5105 and [(18)F]THK5351, [(18)F]AV1451(T807) [(11)C]PBB3, (18)F-THK5117, [(18)F]T808, 18F-RO6958948." ], "exact_answer": [ [ "[(11)C]PBB3" ], [ "[(18)F]AV1451", "T807" ], [ "[(18)F]T808" ], [ "[(18)F]THK523" ], [ "[(18)F]THK5105" ], [ "[(18)F]THK5117" ], [ "[(18)F]THK5351" ], [ "18F-RO6958948" ] ], "type": "list", "id": "5a7d5580faa1ab7d2e00001a", "snippets": [ { "offsetInBeginSection": 586, "offsetInEndSection": 963, "text": "The recent development of selective in-vivo tau PET imaging ligands including [(18)F]THK523, [(18)F]THK5117, [(18)F]THK5105 and [(18)F]THK5351, [(18)F]AV1451(T807) and [(11)C]PBB3 has provided information about the role of tau in the early phases of neurodegenerative diseases, and provided support for diagnosis, prognosis, and imaging biomarkers to track disease progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26572762", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 891, "text": "Tau positron emission tomography radiolabelled probes such as T807, THK-5117, and PBB3 can image the pathology of the disease in vivo. The 18F-labeled tau imaging agents 18F-THK-5351, 18F-T807 (18F-AV-1451), and 18F-RO6958948 are presently under evaluation in clinical studies and clinical trials worldwide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27334944", "endSection": "abstract" } ] }, { "body": "What is the Formalin test used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20832171", "http://www.ncbi.nlm.nih.gov/pubmed/28114822", "http://www.ncbi.nlm.nih.gov/pubmed/1688935", "http://www.ncbi.nlm.nih.gov/pubmed/22453493", "http://www.ncbi.nlm.nih.gov/pubmed/3347367", "http://www.ncbi.nlm.nih.gov/pubmed/23308208", "http://www.ncbi.nlm.nih.gov/pubmed/8731171", "http://www.ncbi.nlm.nih.gov/pubmed/8628579", "http://www.ncbi.nlm.nih.gov/pubmed/23583574", "http://www.ncbi.nlm.nih.gov/pubmed/1484716", "http://www.ncbi.nlm.nih.gov/pubmed/24847424", "http://www.ncbi.nlm.nih.gov/pubmed/6493793", "http://www.ncbi.nlm.nih.gov/pubmed/27987222", "http://www.ncbi.nlm.nih.gov/pubmed/19168051", "http://www.ncbi.nlm.nih.gov/pubmed/27284395", "http://www.ncbi.nlm.nih.gov/pubmed/27716994", "http://www.ncbi.nlm.nih.gov/pubmed/22891086", "http://www.ncbi.nlm.nih.gov/pubmed/25436084", "http://www.ncbi.nlm.nih.gov/pubmed/9431444", "http://www.ncbi.nlm.nih.gov/pubmed/28073097", "http://www.ncbi.nlm.nih.gov/pubmed/15172765" ], "ideal_answer": [ "And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. ", "And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test.", "Persistent pain, In vivo antinociceptive activity, is produced by peripheral tissue injury and inflammation and is modeled by formalin test." ], "exact_answer": [ "pain modeling" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004195", "https://meshb.nlm.nih.gov/record/ui?ui=D010147" ], "type": "factoid", "id": "5abbfd97fcf456587200001d", "snippets": [ { "offsetInBeginSection": 681, "offsetInEndSection": 784, "text": "And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27716994", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 201, "text": "The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27987222", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 470, "text": " experimental nociception using formalin test", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28073097", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 658, "text": "In vivo antinociceptive activity (formalin test) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28114822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "The formalin test has been used in monkeys for assessing pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6493793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Moreover, by using selective antagonists, the role of 5-HT1B/1D serotonergic receptors was investigated in the antinociception induced by these antimigraine drugs.The formalin test was used to assess the nociceptive activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23583574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "In this study, we examined the effect of systemic morphine on Fos-like immunoreactivity (FLI) evoked in the formalin test, a widely used model of persistent pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1688935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The formalin test for nociception, predominantly used with rodents, is characterized by continuous pain due to tissue injury induced by formalin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9431444", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1365, "text": "The orofacial formalin test can then be considered as a reliable way of producing and quantifying nociception in the trigeminal region of the rat.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15172765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The formalin test is used as a primary behavioural screen for assaying the antinociceptive activity of compounds in laboratory rodents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19168051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "The formalin test is the most accepted chemical test for evaluation of nociception.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27284395", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 952, "text": "Nociceptive responses were measured by formalin test (50\u00b5l injection of formalin 2% subcutaneously into hind paw) and pain related behaviors were monitored for 90 min.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24847424", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 119, "text": "Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "The rat paw formalin test is a model of prolonged pain due to mild tissue injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8628579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The formalin test is increasingly applied as a model of inflammatory pain using high formalin concentrations (5-15%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23308208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Although the formalin test is a widely used model of persistent pain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20832171", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 430, "text": "formalin tests were used for the study of pain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22453493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "While the formalin test is a widely used behavioral model of tonic chemogenic pain,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8731171", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 232, "text": "The formalin test, which is based on these observations, is now widely used as a model of pain produced by tissue injury, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1484716", "endSection": "abstract" } ] }, { "body": "What drug treatment can cause a spinal epidural hematoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28255506", "http://www.ncbi.nlm.nih.gov/pubmed/12520314", "http://www.ncbi.nlm.nih.gov/pubmed/26074484", "http://www.ncbi.nlm.nih.gov/pubmed/2797370", "http://www.ncbi.nlm.nih.gov/pubmed/15043358", "http://www.ncbi.nlm.nih.gov/pubmed/27923756", "http://www.ncbi.nlm.nih.gov/pubmed/23351908", "http://www.ncbi.nlm.nih.gov/pubmed/27347652" ], "ideal_answer": [ "Spinal epidural hematoma (SEH) is a rare disease that causes cord compression and neurologic deficit. Spontaneous SEH is related to minor trauma, bleeding disorders, and anticoagulant medications.", "Spinal epidural hematomas are rare entity in neurosurgery practice. Most of them are spontaneous due to anticoagulant therapy and called spontaneous spinal epidural hematomas (SSEHs).", "Spinal epidural hematoma (SEH) is a rare disease that causes cord compression and neurologic deficit.pinal subdural hematoma associated with antiplatelet therapy" ], "exact_answer": [ "Anticoagulant therapy" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D006407", "https://meshb.nlm.nih.gov/record/ui?ui=D046748" ], "type": "factoid", "id": "5ab90a79fcf456587200001b", "snippets": [ { "offsetInBeginSection": 4, "offsetInEndSection": 187, "text": "Spinal epidural hematomas are rare entity in neurosurgery practice. Most of them are spontaneous due to anticoagulant therapy and called spontaneous spinal epidural hematomas (SSEHs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27347652", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 210, "text": "Spinal epidural hematoma (SEH) is a rare disease that causes cord compression and neurologic deficit. Spontaneous SEH is related to minor trauma, bleeding disorders, and anticoagulant medications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28255506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Chronic Spinal Subdural Hematoma Associated with Antiplatelet Therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27923756", "endSection": "title" }, { "offsetInBeginSection": 744, "offsetInEndSection": 804, "text": "pinal subdural hematoma associated with antiplatelet therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27923756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The authors report a case of acute spinal epidural hematoma occurring in a patient receiving antiplatelet drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2797370", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 177, "text": " Spontaneous epidural hematoma of the spine (SEHS) is an extremely rare entity. Patients known to have thrombophilia or on anticoagulant drugs are the most affected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26074484", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 1430, "text": "Most cases of spinal hematoma have a multifactorial etiology whose individual components are not all understood in detail. In up to a third of cases (29.7%) of spinal hematoma, no etiological factor can be identified as the cause of the bleeding. Following idiopathic spinal hematoma, cases related to anticoagulant therapy and vascular malformations represent the second and third most common categories. Spinal and epidural anesthetic procedures in combination with anticoagulant therapy represent the fifth most common etiological group and spinal and epidural anesthetic procedures alone represent the tenth most common cause of spinal hematoma. Anticoagulant therapy alone probably does not trigger spinal hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 436, "text": "We report the case of a man of 65 who, at 20 and 37 days from surgery of C6 corpectomy, experienced two epidural hematomas at C7-D1. We assume that the pathogenic cause of this rare disease was an overlap between three main factors: the surgical aggression of the internal anterior epidural venous plexus; a possible increase of intra-thoracic pressure due to chronic obstructive pulmonary disease; and double antiplatelet drug therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23351908", "endSection": "abstract" } ] }, { "body": "List diseases caused by protein glutamine expanded repeats", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9735324", "http://www.ncbi.nlm.nih.gov/pubmed/22905336", "http://www.ncbi.nlm.nih.gov/pubmed/10381356", "http://www.ncbi.nlm.nih.gov/pubmed/10434299" ], "ideal_answer": [ "Huntington's Disease,\ndentatorubral-pallidoluysian atrophy" ], "exact_answer": [ [ "Huntington's Disease" ], [ "Dentatorubral-pallidoluysian atrophy" ] ], "type": "list", "id": "5ac2776195d0062724000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Huntington's Disease (HD) is a fatally inherited neurodegenerative disorder caused by an expanded glutamine repeat in the N-terminal region of the huntingtin (HTT) protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22905336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "An increasing number of neurodegenerative disorders have been found to be caused by expanding CAG triplet repeats that code for polyglutamine. Huntington's disease (HD) is the most common of these disorders and dentatorubral-pallidoluysian atrophy (DRPLA) is very similar to HD, but is caused by mutation in a different gene, making them good models to study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10434299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Dentatorubral-pallidoluysian atrophy (DRPLA) is caused by expansion of a glutamine repeat in DRPLA protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10381356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The genetic defect in dentatorubral-pallidoluysian atrophy (DRPLA) is expansion of the CAG repeat. The mutant gene is translated into the protein which carries the expanded glutamine repeat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9735324", "endSection": "abstract" } ] }, { "body": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23124521" ], "ideal_answer": [ "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment.", "Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.", "Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level", "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells.", "Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.", "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level", "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. ", "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. ", "In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level.", "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level", "Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. " ], "exact_answer": [ "A/T rich sequences" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D034921", "https://meshb.nlm.nih.gov/record/ui?ui=D034882", "https://meshb.nlm.nih.gov/record/ui?ui=D001482", "https://meshb.nlm.nih.gov/record/ui?ui=D034904" ], "type": "factoid", "id": "5a86e6fafaa1ab7d2e000036", "snippets": [ { "offsetInBeginSection": 731, "offsetInEndSection": 1267, "text": "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124521", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1269, "text": "In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23124521", "endSection": "abstract" } ] }, { "body": "What is the clathrin triskelia structure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18502808", "http://www.ncbi.nlm.nih.gov/pubmed/16669634", "http://www.ncbi.nlm.nih.gov/pubmed/22704991" ], "ideal_answer": [ "The clathrin triskelion, which is a three-legged pinwheel-shaped heteropolymer, is a major component in the protein coats of certain post-Golgi and endocytic vesicles." ], "exact_answer": [ "A three-legged pinwheel-shaped heteropolymer." ], "type": "factoid", "id": "5ad4dd93133db5eb78000008", "snippets": [ { "offsetInBeginSection": 653, "offsetInEndSection": 771, "text": "Clathrin assembles into triskelia composed of three clathrin heavy chains and associated clathrin light chains (CLCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "A principal component in the protein coats of certain post-golgi and endocytic vesicles is clathrin, which appears as a three-legged heteropolymer (known as a triskelion) that assembles into polyhedral cages principally made up of pentagonal and hexagonal faces. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16669634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The clathrin triskelion, which is a three-legged pinwheel-shaped heteropolymer, is a major component in the protein coats of certain post-Golgi and endocytic vesicles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18502808", "endSection": "abstract" } ] }, { "body": "What is myelin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21343408", "http://www.ncbi.nlm.nih.gov/pubmed/27638763", "http://www.ncbi.nlm.nih.gov/pubmed/25682762", "http://www.ncbi.nlm.nih.gov/pubmed/21720767", "http://www.ncbi.nlm.nih.gov/pubmed/27829268", "http://www.ncbi.nlm.nih.gov/pubmed/27235538", "http://www.ncbi.nlm.nih.gov/pubmed/28925106", "http://www.ncbi.nlm.nih.gov/pubmed/29054040", "http://www.ncbi.nlm.nih.gov/pubmed/23780694" ], "ideal_answer": [ "Myelin is a specialized structure of the nervous system that covers the neuron and both enhances electrical conductance and insulates neurons from external risk factors." ], "concepts": [ "http://amigo.geneontology.org/amigo/term/GO:0043209", "https://meshb.nlm.nih.gov/record/ui?ui=D009185", "https://meshb.nlm.nih.gov/record/ui?ui=D009186" ], "type": "summary", "id": "5abcf108fcf4565872000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Myelination is a recent evolutionary addition that significantly enhances the speed of transmission in the neural network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27235538", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 531, "text": ". Myelin is only formed by fully differentiated oligodendrocytes, but the entire oligodendrocyte lineage are clear targets of the altered chemistry of the aging brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27235538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Formation of myelin sheaths by Schwann cells (SCs) enables rapid and efficient transmission of action potentials in peripheral axons, and disruption of myelination results in disorders that involve decreased sensory and motor functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27638763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27829268", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 321, "text": "polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27829268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Myelin - the multilayer membrane that envelops axons - is a facilitator of rapid nerve conduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25682762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Myelin allows for the rapid and precise timing of action potential propagation along neuronal circuits and is essential for healthy auditory system function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28925106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Myelin sheaths in the vertebrate nervous system enable faster impulse propagation, while myelinating glia provide vital support to axons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29054040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Myelin consists of tightly compacted membranes that form an insulating sheath around axons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21343408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Myelin is a biologically active mutilamellar that is formed by oligodendrocytes (OLs) in the central nervous system (CNS) and ensheathes axons ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21720767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "The myelin sheath is a multilayered membrane in the nervous system, which has unique biochemical properties. Myelin carries a set of specific high-abundance proteins, the structure and function of which are still poorly understood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23780694", "endSection": "abstract" } ] }, { "body": "Is Brucella abortus the organism that causes brucillosis known to cause spontaneous abortions in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18390151", "http://www.ncbi.nlm.nih.gov/pubmed/24480149", "http://www.ncbi.nlm.nih.gov/pubmed/18387752", "http://www.ncbi.nlm.nih.gov/pubmed/22826490", "http://www.ncbi.nlm.nih.gov/pubmed/17296251", "http://www.ncbi.nlm.nih.gov/pubmed/22194770", "http://www.ncbi.nlm.nih.gov/pubmed/24609497", "http://www.ncbi.nlm.nih.gov/pubmed/16739129", "http://www.ncbi.nlm.nih.gov/pubmed/24762925", "http://www.ncbi.nlm.nih.gov/pubmed/20140321", "http://www.ncbi.nlm.nih.gov/pubmed/16368972", "http://www.ncbi.nlm.nih.gov/pubmed/22636321", "http://www.ncbi.nlm.nih.gov/pubmed/28167945", "http://www.ncbi.nlm.nih.gov/pubmed/26578650", "http://www.ncbi.nlm.nih.gov/pubmed/12183550", "http://www.ncbi.nlm.nih.gov/pubmed/3929401", "http://www.ncbi.nlm.nih.gov/pubmed/22566755" ], "ideal_answer": [ "Human brucellosis symptoms and clinical signs most commonly reported are fever, fatigue, malaise, chills, sweats headaches, myalgia, arthralgia, and weight loss. Some cases have been presented with only joint pain, lower backache, and involuntary limb movement, burning feet, or ischemic heart attacks." ], "exact_answer": "no", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:14457", "https://meshb.nlm.nih.gov/record/ui?ui=D002003", "https://meshb.nlm.nih.gov/record/ui?ui=D002006" ], "type": "yesno", "id": "5aa6800ad6d6b54f79000011", "snippets": [ { "offsetInBeginSection": 122, "offsetInEndSection": 187, "text": ". Brucellosis is a major cause of pyrexia of unknown origin (PUO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24762925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Brucellosis is the most common bacterial zoonosis, and causes a considerable burden of disease in endemic countries. Cardiovascular involvement is the main cause of mortality due to infection with Brucella spp,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24480149", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 706, "text": "quite abruptly, he developed asthenia and hypersomnia without any apparent cause or symptoms like fever, chills, or night sweats. On November 14, 2009, he suffered from pain and edema in the right testicle that coincided with pain in the abdomen. Clinical, serological, and bacteriological investigations confirmed the first case of unilateral orchitis in man in Ecuador caused by Brucella abortus biovar 1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22826490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Brucellosis is not frequent in Chile but it may present with life threatening complications like endocarditis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Human brucellosis exhibits diverse pathological manifestations that can affect almost any organ. In particular, osteoarticular complications are the most common focal manifestation of brucellosis and occur in 40-80% of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22636321", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 506, "text": "Brucella. Human brucellosis often makes the diagnosis difficult. The symptoms and clinical signs most commonly reported are fever, fatigue, malaise, chills, sweats headaches, myalgia, arthralgia, and weight loss. Some cases have been presented with only joint pain, lower backache, and involuntary limb movement, burning feet, or ischemic heart attacks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22566755", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 846, "text": "Forty-five cases were collected (31 acute and 14 sub-acute). Contamination was digestive in 62%. Symptoms of patients were fever (93%), sweating (82%), arthralgia (78%) and splenomegaly (51%). Elevated erythrocyte sedimentation rate was determined in 80%, leukopenia in 49% and anaemia in 37% of cases. Blood cultures were positives in 39% of cases. The four sequenced strains were identified as Brucella melitensis biovar abortus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18387752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "It is also known to cause persistent undulant fever, endocarditis, arthritis, osteomyelitis and meningitis in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17296251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Brucella abortus is a Gram-negative intracellular bacterial pathogen that causes a zoonosis of worldwide occurrence, leading to undulant fever in humans and abortion in domestic animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26578650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12183550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Brucella abortus is a facultative, intracellular zoonotic pathogen which can cause undulant fever in humans and abortions in cattle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16368972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Brucella abortus is a Gram-negative, facultative intracellular bacterium that causes brucellosis, a worldwide zoonotic disease leading to undulant fever in humans and abortion in cattle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28167945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22194770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Brucella abortus is a gram-negative, facultative intracellular pathogen that causes brucellosis, a chronic zoonotic disease resulting in abortion in pregnant cattle and undulant fever in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24609497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Brucella abortus is a bacterium which causes abortions and infertility in cattle and undulant fever in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Brucella abortus is the etiologic agent of bovine brucellosis and causes a chronic disease in humans known as undulant fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16739129", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 735, "text": "No case of acute Brucella infection was demonstrated; however, there were 5 cases in which the serological finding was consistent with chronic brucellosis (4%). In all these cases no positive evidence of close animal contact could be found; furthermore of the 12,1% of women who actually handled domestic animals, only 1 had a history of previous abortion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3929401", "endSection": "abstract" } ] }, { "body": "What percentage of Homo sapiens DNA is of Neanderthal origin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18768141", "http://www.ncbi.nlm.nih.gov/pubmed/24336922", "http://www.ncbi.nlm.nih.gov/pubmed/27038113", "http://www.ncbi.nlm.nih.gov/pubmed/23872234", "http://www.ncbi.nlm.nih.gov/pubmed/27824859", "http://www.ncbi.nlm.nih.gov/pubmed/26392408" ], "ideal_answer": [ "We find that the power to reject ancient admixture might be particularly low if the population size of Homo sapiens was comparable to the Neanderthal population size. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe.", "Approximately 2-4% of genetic material in human populations outside Africa is derived from Neanderthals who interbred with anatomically modern humans. 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe.", "Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Here, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans.", "3.6 % of the neanderthal genome is shared with roughly 65.4 % of the average european gene pool , which clinally diminishes with distance from europe.This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought." ], "exact_answer": [ "2-4%" ], "type": "factoid", "id": "5ace1a590340b9f05800000b", "snippets": [ { "offsetInBeginSection": 998, "offsetInEndSection": 1164, "text": "We find that the power to reject ancient admixture might be particularly low if the population size of Homo sapiens was comparable to the Neanderthal population size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18768141", "endSection": "abstract" }, { "offsetInBeginSection": 1395, "offsetInEndSection": 1568, "text": "Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23872234", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 311, "text": "Here, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336922", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 411, "text": "This introgression was under positive natural selection, reached a frequency of>50%, and introduced a homocysteine level- and pigmentation-associated allele (rs460879-T) into East Asians. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26392408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Hybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824859", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1492, "text": "This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824859", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Approximately 2-4% of genetic material in human populations outside Africa is derived from Neanderthals who interbred with anatomically modern humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27038113", "endSection": "abstract" } ] }, { "body": "What is Dupuytren's contracture?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17145384", "http://www.ncbi.nlm.nih.gov/pubmed/28138723", "http://www.ncbi.nlm.nih.gov/pubmed/21992150", "http://www.ncbi.nlm.nih.gov/pubmed/28175956", "http://www.ncbi.nlm.nih.gov/pubmed/28841903", "http://www.ncbi.nlm.nih.gov/pubmed/18847012", "http://www.ncbi.nlm.nih.gov/pubmed/28732844" ], "ideal_answer": [ "Dupuytren's contracture is a progressive hand condition that affects how much you can move or straighten your fingers. It is a benign fibroproliferative disease leads to hyperplasia of the collagen fibers of the fascia of the palm, which can result in severe impairment of the functionality of the hand." ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D004387" ], "type": "summary", "id": "5abcf66afcf4565872000026", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 213, "text": "Dupuytren's disease as a\u00a0benign fibroproliferative disease leads to hyperplasia of the collagen fibers of the fascia of the palm, which can result in severe impairment of the functionality of the hand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28138723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Dupuytren disease is a\u00a0benign fibroproliferative disease of the palmar aponeurosis, which can cause considerable functional deficiencies for the person concerned", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28175956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Dupuytren's contracture is a common hand problem that affects the palmar fascia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28732844", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 207, "text": " Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28841903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Dupuytren's contracture is a connective tissue disorder characterized by contractile palmar aponeurosis leading to shortening and progressive digital flexion deformity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18847012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "PURPOSE Dupuytren's contracture is a fibroproliferative disorder of the hand characterized by an abnormal myofibroblast and fibroblast proliferation and extracellular matrix deposition leading to retraction and deformation of the palm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17145384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Dupuytren's contracture is a condition of the palmar fascia involving contractures of the fascia and skin in the hand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21992150", "endSection": "abstract" } ] }, { "body": "What phenotype is associated with the V60L mutation in the human MC1R gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18366057", "http://www.ncbi.nlm.nih.gov/pubmed/12851335", "http://www.ncbi.nlm.nih.gov/pubmed/12851336", "http://www.ncbi.nlm.nih.gov/pubmed/21615505", "http://www.ncbi.nlm.nih.gov/pubmed/17616515", "http://www.ncbi.nlm.nih.gov/pubmed/11030758", "http://www.ncbi.nlm.nih.gov/pubmed/15972726", "http://www.ncbi.nlm.nih.gov/pubmed/25794181", "http://www.ncbi.nlm.nih.gov/pubmed/26042826", "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "http://www.ncbi.nlm.nih.gov/pubmed/24045876", "http://www.ncbi.nlm.nih.gov/pubmed/12006619", "http://www.ncbi.nlm.nih.gov/pubmed/19924138", "http://www.ncbi.nlm.nih.gov/pubmed/18637132", "http://www.ncbi.nlm.nih.gov/pubmed/26103569" ], "ideal_answer": [ "The characterization of the melanocortin 1 receptor (MC1R) expressed on human melanocytes and the findings that certain mutations in the POMC gene or the MC1R gene result in red hair phenotype underscore the significance of melanocortins and MC1R in regulating human pigmentation. We describe a minisequencing protocol for screening DNA samples for the presence of 12 mutations in the human melanocortin 1 receptor gene (MC1R), eight of which are associated with the red hair phenotype. The human MC1R gene is highly polymorphic and certain allelic variants of the gene are associated with red hair phenotype, melanoma and non-melanoma skin cancer. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. These loss-of-function mutations have been associated with red hair phenotype and increased risk for skin cancer. Alleles associated with the red hair color (RHC) phenotype and with the risk of melanoma were examined.", "Red hair is usually inherited as a recessive characteristic with the R151C, R160W, D294H, R142H, 86insA and 537insC alleles at this locus. The V60L variant, which is common in the population may act as a partially penetrant recessive allele. V60L is a mutation also associated to red hair and fair skin and even blonde hair.", "The V60L variant, which is common in the population may act as a partially penetrant recessive allele. Both of these Thr(111)/Ala(111) heterozygotes carried a single polymorphism of MC1R (one with the V92M variant and another with the V60L variant) different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair) Genetic association and cellular function of MC1R variant alleles in human pigmentation." ], "type": "summary", "id": "5ace2d600340b9f05800000e", "snippets": [ { "offsetInBeginSection": 606, "offsetInEndSection": 734, "text": "An additional three low-penetrance alleles V60L, V92M, and R163Q have odds ratios 6, 5, and 2 relative to the wild-type allele. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12851335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Genetic association and cellular function of MC1R variant alleles in human pigmentation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12851335", "endSection": "title" }, { "offsetInBeginSection": 319, "offsetInEndSection": 737, "text": "We have investigated 174 individuals from 11 large kindreds with a preponderance of red hair and an additional 99 unrelated redheads, for MC1R variants and have confirmed that red hair is usually inherited as a recessive characteristic with the R151C, R160W, D294H, R142H, 86insA and 537insC alleles at this locus. The V60L variant, which is common in the population may act as a partially penetrant recessive allele. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11030758", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 627, "text": "In vitro expression studies revealed that variant receptors with reduced cell surface expression, including V60L, D84E, R151C, I155T, R160W and R163Q, showed a corresponding impairment in cAMP coupling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17616515", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 659, "text": "Among the fifteen MC1R variants identified, the nine most common were V60L, V92M, R151C, R160W, R163Q, R142H, D294H, D84E, and I155T.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19924138", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 781, "text": "Both of these Thr(111)/Ala(111) heterozygotes carried a single polymorphism of MC1R (one with the V92M variant and another with the V60L variant)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18637132", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 514, "text": "The V60L-/- homozygote r variant cells showed similar responses to ligand as WT MC1R strains, while V92M-/- homozygote r variant cells were generally shown to have greater dendricity and express higher DCT than the WT cells, even at basal levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21615505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Simultaneous purifying selection on the ancestral MC1R allele and positive selection on the melanoma-risk allele V60L in south Europeans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045876", "endSection": "title" }, { "offsetInBeginSection": 797, "offsetInEndSection": 928, "text": "different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045876", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1131, "text": "All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26103569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "The characterization of the melanocortin 1 receptor (MC1R) expressed on human melanocytes and the findings that certain mutations in the POMC gene or the MC1R gene result in red hair phenotype underscore the significance of melanocortins and MC1R in regulating human pigmentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12851336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "We describe a minisequencing protocol for screening DNA samples for the presence of 12 mutations in the human melanocortin 1 receptor gene (MC1R), eight of which are associated with the red hair phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11672965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The human MC1R gene is highly polymorphic and certain allelic variants of the gene are associated with red hair phenotype, melanoma and non-melanoma skin cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12006619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "These loss-of-function mutations have been associated with red hair phenotype and increased risk for skin cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12851336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Alleles associated with the red hair color (RHC) phenotype and with the risk of melanoma were examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794181", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 1010, "text": "Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24045876", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1244, "text": "The combination of the prediction tools results in 14 nsSNPs indicated as the most damaging mutations in MC1R (L48P, R67W, H70Y, P72L, S83P, R151H, S172I, L206P, T242I, G255R, P256S, C273Y, C289R and R306H); C273Y showed to be highly damaging in SIFT, Polyphen-2, MutPred, PANTHER and PROVEAN scores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794181", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1312, "text": "In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26103569", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1659, "text": "These results indicate that reduced receptor coupling activity may not be the only contributing factor to the genetic association between the MC1R variants and the RHC phenotype, with MC1R polymorphisms now linked to a change in receptor localization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15972726", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 421, "text": "Here we used 11 computational tools based on different approaches to predict the damage-associated non-synonymous single nucleotide polymorphisms (nsSNPs) in the coding region of the human MC1R gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Variants of the melanocortin 1 receptor (MC1R) gene are common in individuals with red hair and fair skin, but the relative contribution to these pigmentary traits in heterozygotes, homozygotes and compound heterozygotes for variants at this locus from the multiple alleles present in Caucasian populations is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11030758", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 725, "text": "Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26042826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26042826", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 527, "text": "The human MC1R gene is highly polymorphic and certain allelic variants of the gene are associated with red hair phenotype, melanoma and non-melanoma skin cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12006619", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 217, "text": "Several MC1R variant alleles are associated with red hair, fair skin and increased skin cancer risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17616515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Prediction of the damage-associated non-synonymous single nucleotide polymorphisms in the human MC1R gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794181", "endSection": "title" }, { "offsetInBeginSection": 198, "offsetInEndSection": 419, "text": "We performed a meta-analysis on the association between the 9 most studied MC1R variants (p.V60L, p.D84E, p.V92M, p.R142H, p.R151C, p.I155T, p.R160W, p.R163Q and p.D294H) and melanoma and/or red hair, fair skin phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18366057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15972726", "endSection": "title" } ] }, { "body": "List proteins with HEAT repeats", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28512144", "http://www.ncbi.nlm.nih.gov/pubmed/27072897", "http://www.ncbi.nlm.nih.gov/pubmed/24120762", "http://www.ncbi.nlm.nih.gov/pubmed/28415797", "http://www.ncbi.nlm.nih.gov/pubmed/27066066", "http://www.ncbi.nlm.nih.gov/pubmed/26676747", "http://www.ncbi.nlm.nih.gov/pubmed/27549742", "http://www.ncbi.nlm.nih.gov/pubmed/27742610", "http://www.ncbi.nlm.nih.gov/pubmed/22315229", "http://www.ncbi.nlm.nih.gov/pubmed/28668119" ], "ideal_answer": [ "mTOR,\nTOG5, \nDNA-PKcs,\nHEATR1,\nRif1,\nB56\u03b3,\nPR65/A,\nSF3b155,\nPds5B" ], "exact_answer": [ [ "mTOR" ], [ "TOG5" ], [ "DNA-PKcs" ], [ "HEATR1" ], [ "Rif1" ], [ "B56\u03b3" ], [ "PR65/A" ], [ "SF3b155" ], [ "Pds5B" ] ], "type": "list", "id": "5abd44b1fcf4565872000030", "snippets": [ { "offsetInBeginSection": 835, "offsetInEndSection": 869, "text": "mTOR N-terminal heat repeat domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28415797", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 726, "text": "TOG5-specific N-terminal HEAT repeat ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28512144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is central to the regulation of the DNA damage response and repair through nonhomologous end joining. The structure has proved challenging due to its large size and multiple HEAT repeats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28668119", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 265, "text": "HEAT repeat-containing protein 1 (HEATR1) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26676747", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 716, "text": "The first 1,300 residues of Tor form a HEAT repeat-containing \u03b1-solenoid with four distinct segments: a highly curved 800-residue N-terminal 'spiral', followed by a 400-residue low-curvature 'bridge' and an extended 'railing' running along the bridge leading to the 'cap' that links to FAT region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072897", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 591, "text": "Rif1 proteins are large and characterized by N-terminal HEAT repeats, predicted to form an elongated alpha-helical structure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27066066", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 689, "text": "B56\u03b3 contains 18 \u03b1-helices that are organized into eight HEAT (Huntington-elongation-A subunit-TOR) repeat motifs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22315229", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Here, we reveal a remarkable complexity in the unfolding of giant HEAT-repeat protein PR65/A, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24120762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "A HEAT-repeat superhelix within SF3b155 plays a key role in branch site recognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27742610", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 658, "text": "The HEAT-repeat protein Pds5B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27549742", "endSection": "abstract" } ] }, { "body": "What is the aim of perfoming a \"cycloheximide chase assay\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21518760", "http://www.ncbi.nlm.nih.gov/pubmed/27987332", "http://www.ncbi.nlm.nih.gov/pubmed/21953463", "http://www.ncbi.nlm.nih.gov/pubmed/28880013", "http://www.ncbi.nlm.nih.gov/pubmed/23962426", "http://www.ncbi.nlm.nih.gov/pubmed/29082276" ], "ideal_answer": [ "Comparison of protein stability in eukaryotic cells has been achieved by cycloheximide, which is an inhibitor of protein biosynthesis due to its prevention in translational elongation. It is broadly used in cell biology in terms of determining the half-life of a given protein and has gained much popularity in cancer research." ], "type": "summary", "id": "5ac08478d0c506ce46000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Analysis of Protein Stability by the Cycloheximide Chase Assay.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29082276", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 452, "text": "Comparison of protein stability in eukaryotic cells has been achieved by cycloheximide, which is an inhibitor of protein biosynthesis due to its prevention in translational elongation. It is broadly used in cell biology in terms of determining the half-life of a given protein and has gained much popularity in cancer research. Here we present a full cycloheximide chase assay in our laboratory using a lung adenocarcinoma cell line, CL1-5, as a model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29082276", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1385, "text": ". In addition, cycloheximide chase assay revealed that the half-life of VE-cadherin protein was dramatically reduced by Cullin 3 depletion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27987332", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 811, "text": " After blocking transcription and translation processes with actinomycin D and cycloheximide, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28880013", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1013, "text": "The cycloheximide chase assay revealed that an S410L mutation in the Kelch domain significantly decreased the intracellular stability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23962426", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 935, "text": "Cycloheximide chase assay showed a decrease in the half-life of KLF8 protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21518760", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 745, "text": "SMURF2 alone reduced the protein stability of KLF5 as shown by cycloheximide chase assay, indicating that SMURF2 specifically destabilizes KLF5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21953463", "endSection": "abstract" } ] }, { "body": "What is an exosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28733901", "http://www.ncbi.nlm.nih.gov/pubmed/32722531", "http://www.ncbi.nlm.nih.gov/pubmed/11188932", "http://www.ncbi.nlm.nih.gov/pubmed/18331451", "http://www.ncbi.nlm.nih.gov/pubmed/27018079", "http://www.ncbi.nlm.nih.gov/pubmed/31316512", "http://www.ncbi.nlm.nih.gov/pubmed/30665462", "http://www.ncbi.nlm.nih.gov/pubmed/24095986", "http://www.ncbi.nlm.nih.gov/pubmed/28930577", "http://www.ncbi.nlm.nih.gov/pubmed/29071676", "http://www.ncbi.nlm.nih.gov/pubmed/22200143", "http://www.ncbi.nlm.nih.gov/pubmed/22982408", "http://www.ncbi.nlm.nih.gov/pubmed/26198793", "http://www.ncbi.nlm.nih.gov/pubmed/27296830", "http://www.ncbi.nlm.nih.gov/pubmed/22648975", "http://www.ncbi.nlm.nih.gov/pubmed/34069542", "http://www.ncbi.nlm.nih.gov/pubmed/26667071", "http://www.ncbi.nlm.nih.gov/pubmed/31840492", "http://www.ncbi.nlm.nih.gov/pubmed/29054369", "http://www.ncbi.nlm.nih.gov/pubmed/25398455", "http://www.ncbi.nlm.nih.gov/pubmed/26393640", "http://www.ncbi.nlm.nih.gov/pubmed/10984428", "http://www.ncbi.nlm.nih.gov/pubmed/20145139", "http://www.ncbi.nlm.nih.gov/pubmed/21645191", "http://www.ncbi.nlm.nih.gov/pubmed/28095652", "http://www.ncbi.nlm.nih.gov/pubmed/28718905", "http://www.ncbi.nlm.nih.gov/pubmed/15346807", "http://www.ncbi.nlm.nih.gov/pubmed/28446531" ], "ideal_answer": [ "Exosomes are a subset of extracellular vesicles (EVs) that have important roles in intercellular communication. They contain and carry bioactive molecules within their membranes which are delivered to target cells." ], "exact_answer": [ "Exosomes are a subset of extracellular vesicles (EVs) that have important roles in intercellular communication. They contain and carry bioactive molecules within their membranes which are delivered to target cells." ], "type": "factoid", "id": "5ac0a36f19833b0d7b000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Exosomes are small extracellular membrane-based vesicles with a variety of cargoes that are involved in numerous physiological and pathological processes in the nervous system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28718905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Exosomes are a subset of extracellular vesicles (EVs) that have important roles in intercellular communication. They contain and carry bioactive molecules within their membranes which are delivered to target cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28930577", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Extracellular vesicles (EVs) are released by cells and can be found in cell culture supernatants and biofluids. EVs carry proteins, nucleic acids, and other cellular components and can deliver these to nearby or distant cells, making EVs of interest as both disease biomarkers and therapeutic targets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29071676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Exosomes are released by cells as self-contained vesicles with an intact lipid bilayer that encapsulates a small portion of the parent cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27018079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Exosomes are a type of cell-derived extracellular nanovesicle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22648975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Exosomes are small extracellular vesicles released to the extracellular milieu through fusion of multivesicular bodies with the plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22982408", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 269, "text": "Exosomes are natural products released from many sources and play a role in antigen presentation, immunoregulation, and signal transduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24095986", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 155, "text": " Exosomes, cell-derived vesicles encompassing lipids, DNA, proteins coding genes and noncoding RNAs (ncRNAs) are present in diverse body fluids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28446531", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 270, "text": "Exosomes are 60-80 nm vesicles of endocytic origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11188932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Exosomes are small membrane vesicles, secreted by most cell types from multivesicular endosomes, and thought to play important roles in intercellular communications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21645191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Exosomes are extracellular vesicles first described as such 30\u00a0years ago and since implicated in cell-cell communication and the transmission of disease states, and explored as a means of drug discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27296830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Exosomes are extracellular vesicles released upon fusion of multivesicular bodies(MVBs) with the cellular plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26393640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Exosomes are small vesicles with an average diameter of 100 nm that are produced by many, if not all, cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34069542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The exosome, a molecular machine for controlled RNA degradation in both nucleus and cytoplasm.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15346807", "endSection": "title" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1285, "text": "Exosomes are part of the endocytic system,which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26393640", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 414, "text": "Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26393640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Exosomes are nano-sized vesicles of endocytic origin released into the extracellular space upon fusion of multivesicular bodies with the plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Exosomes are small membrane vesicles that are secreted by a multitude of cell types as a consequence of fusion of multivesicular late endosomes/lysosomes with the plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10984428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32722531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "An exosome (30-150 nm size) is a cell-derived vesicle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31316512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Exosomes are a subtype of vesicles released by cells of both healthy and neoplastic origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22200143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "PURPOSE: Exosomes are small membrane vesicles (30-100nm in diameter) secreted by cells into extracellul", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29054369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Exosome is a mechanism of intercellular drug transfer: Application of quantitative pharmacology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29054369", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Exosomes are the newest family member of 'bioactive vesicles' that function to promote intercellular communication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18331451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28733901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Exosomes are nano-sized membrane vesicles (50-120\u00a0nm), which are released from a wide variety of cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26198793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Exosomes are small extracellular vesicles (EVs) secreted by many cell types in both normal and pathogenic circumstances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28095652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Exosomes are nanovesicles originating from late endosomal compartments and secreted by most living cells in ex vivo cell culture conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20145139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26667071", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 185, "text": "he exosome is a promising biomarker carrying many kinds of membrane proteins with huge heterogeneity, so the sensitive and multiplex analysis of exosomes is very significant for diseas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31840492", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 273, "text": "The RNA exosome is an evolutionarily conserved 3'-5' exoribonucleolytic protein complex involved in processing and degradation of different classes of nuclear and cytoplasmic RNAs, and, therefore, important for the posttranscriptional control of gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30665462", "endSection": "abstract" } ] }, { "body": "Are human enhancers or promoters evolving faster?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24097306", "http://www.ncbi.nlm.nih.gov/pubmed/28527813", "http://www.ncbi.nlm.nih.gov/pubmed/25635462", "http://www.ncbi.nlm.nih.gov/pubmed/21783031", "http://www.ncbi.nlm.nih.gov/pubmed/20023155", "http://www.ncbi.nlm.nih.gov/pubmed/24218635" ], "ideal_answer": [ "Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. ", "We report that rapid evolution of enhancers is a universal feature of mammalian genomes.", "Rapid evolution of enhancers is a universal feature of mammalian genomes." ], "exact_answer": [ "enhancers" ], "type": "factoid", "id": "5ac3699f0340b9f058000001", "snippets": [ { "offsetInBeginSection": 288, "offsetInEndSection": 402, "text": " Recent comparative studies have begun to investigate the evolution of the sequence architecture within enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20023155", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 302, "text": "A detailed analysis of the fast-evolving sparkling enhancer in Drosophila now identifies key compensatory mechanisms and 'grammar' elements that are critical for maintaining functional integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21783031", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1030, "text": "The trend is one of high divergence of cis-regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24218635", "endSection": "abstract" }, { "offsetInBeginSection": 70, "offsetInEndSection": 385, "text": "However, existing models specifically designed for regulatory sequences consider the independent evolution of individual transcription factor (TF)-binding sites, ignoring that the function and evolution of a binding site depends on its context, typically the cis-regulatory module (CRM) in which the site is located", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24097306", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 460, "text": "We summarize recent case studies and genome-wide investigations that have uncovered diverse mechanisms though which new enhancers arise", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28527813", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 465, "text": "We report that rapid evolution of enhancers is a universal feature of mammalian genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635462", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 907, "text": "Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635462", "endSection": "abstract" } ] }, { "body": "What are the 3 antidotes for anticoagulant (anti-blood clotting) drugs, including factor Xa inhibitors, as of November 2017.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27895055", "http://www.ncbi.nlm.nih.gov/pubmed/27789605", "http://www.ncbi.nlm.nih.gov/pubmed/27626268" ], "ideal_answer": [ " two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran, was approved by FDA in October 2015.", " two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran, was approved by FDA in October 2015. Idarucizumab and andexanet alfa have been reported to produce anticoagulation reversal effects within minutes of administration. ", "Two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase." ], "exact_answer": [ [ "Idarucizumab" ], [ "andexanet alfa" ], [ "ciraparantag" ], [ "Protamine sulfate" ], [ "Aripazine" ] ], "type": "list", "id": "5ac0f7b919833b0d7b000006", "snippets": [ { "offsetInBeginSection": 726, "offsetInEndSection": 993, "text": " two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran, was approved by FDA in October 2015.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895055", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1123, "text": "Idarucizumab and andexanet alfa have been reported to produce anticoagulation reversal effects within minutes of administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895055", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1125, "text": "Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789605", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1414, "text": ". Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789605", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 930, "text": "Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789605", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 949, "text": " working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27626268", "endSection": "abstract" } ] }, { "body": "Which genes are associated with Epidermolysis Bullosa Simplex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19797037", "http://www.ncbi.nlm.nih.gov/pubmed/7539246", "http://www.ncbi.nlm.nih.gov/pubmed/9036937", "http://www.ncbi.nlm.nih.gov/pubmed/10494094", "http://www.ncbi.nlm.nih.gov/pubmed/7561171", "http://www.ncbi.nlm.nih.gov/pubmed/21375516", "http://www.ncbi.nlm.nih.gov/pubmed/11159198", "http://www.ncbi.nlm.nih.gov/pubmed/1720261", "http://www.ncbi.nlm.nih.gov/pubmed/9804355", "http://www.ncbi.nlm.nih.gov/pubmed/22639907", "http://www.ncbi.nlm.nih.gov/pubmed/26929861", "http://www.ncbi.nlm.nih.gov/pubmed/20199538", "http://www.ncbi.nlm.nih.gov/pubmed/11407988", "http://www.ncbi.nlm.nih.gov/pubmed/8894687", "http://www.ncbi.nlm.nih.gov/pubmed/20030639", "http://www.ncbi.nlm.nih.gov/pubmed/8941634", "http://www.ncbi.nlm.nih.gov/pubmed/1381443", "http://www.ncbi.nlm.nih.gov/pubmed/12655565", "http://www.ncbi.nlm.nih.gov/pubmed/28777847" ], "ideal_answer": [ "In one family studied, inheritance of EBS is linked to the gene encoding keratin 14", "Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes. A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency.", "In one family studied, inheritance of EBS is linked to the gene encoding keratin 14 Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14.", "Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14.", "Keratin 5 and keratin 14 are known to be essential for the basal keratinocyte cytoskeleton and are defective in several forms of epidermolysis bullosa simplex. Homozygous deletion mutations in the plectin gene in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. The KRT5 and KRT14 genes encode the proteins keratin 5 and 14, respectively, which are the primary structural components of the 10-nm intermediate filaments of the mitotic epidermal basal cells. Epidermolysis bullosa simplex is mainly caused by mutations in the KRT5 and KRT14 genes. Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene. This is the first report of EBS-generalized intermediate in a newborn with de novo KRT5 gene mutation and KRT14 gene polymorphism, and no familial history of epidermolysis. Study of a family with epidermolysis bullosa simplex resulting from a novel mutation of KRT14 gene. We have systematically scanned genomic sequences of one of these keratins, keratin 14, for mutations in patients from 49 apparently independent kindreds using single-strand conformation polymorphism analysis. ", "Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes. Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene.", "Recent advances in molecular biology have enabled the association of epidermolysis bullosa simplex (EBS) with point mutations of keratin 14 and/or keratin 5 genes to be established. ", "Keratin 14 gene mutations in patients with epidermolysis bullosa simplex. Mutant keratins 5 or 14 are implicated in the etiology of epidermolysis bullosa simplex (EBS). Keratin 14 gene point mutation in the K\u00f6bner and Dowling-Meara types of epidermolysis bullosa simplex as detected by the PASA method." ], "exact_answer": [ [ "Keratin 14", "KRT14" ], [ "Keratin 5", "KRT5" ], [ "Plectin", "PLEC1" ] ], "type": "list", "id": "5ace34eb0340b9f058000010", "snippets": [ { "offsetInBeginSection": 109, "offsetInEndSection": 192, "text": "In one family studied, inheritance of EBS is linked to the gene encoding keratin 14", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1720261", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 778, "text": "In the first family, linkage was found to chromosome 17 markers flanking the keratin 14 gene (D17S74: Zmax = +2.45, theta = 0.10; COL1A1: Zmax = +0.97, theta = 0.00) and markers near the keratin 5 gene on chromosome 12 were excluded (D12S17: Z less than -2.0, theta = 0.08; COL2A1: Z less than -2.0, theta = 0.13). In contrast, the second family showed linkage to the region containing the keratin 5 gene (D12S17: Zmax = +1.37, theta = 0.08; COL2A1: Zmax = +0.33, theta = 0.15) and was not linked to the keratin 14 gene (D17S74: Z less than -2.0, theta = 0.14). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1381443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Keratin 14 gene mutations in patients with epidermolysis bullosa simplex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7561171", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 411, "text": "We have systematically scanned genomic sequences of one of these keratins, keratin 14, for mutations in patients from 49 apparently independent kindreds using single-strand conformation polymorphism analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7561171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Keratin 14 gene point mutation in the K\u00f6bner and Dowling-Meara types of epidermolysis bullosa simplex as detected by the PASA method.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7539246", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Recent advances in molecular biology have enabled the association of epidermolysis bullosa simplex (EBS) with point mutations of keratin 14 and/or keratin 5 genes to be established. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7539246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8894687", "endSection": "title" }, { "offsetInBeginSection": 447, "offsetInEndSection": 566, "text": " In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8894687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "A homozygous nonsense mutation in the PLEC1 gene in patients with epidermolysis bullosa simplex with muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8941634", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11159198", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The KRT5 and KRT14 genes encode the proteins keratin 5 and 14, respectively, which are the primary structural components of the 10-nm intermediate filaments of the mitotic epidermal basal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9036937", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 447, "text": "Keratin 5 and keratin 14 are known to be essential for the basal keratinocyte cytoskeleton and are defective in several forms of epidermolysis bullosa simplex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10494094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Severe palmo-plantar hyperkeratosis in Dowling-Meara epidermolysis bullosa simplex caused by a mutation in the keratin 14 gene (KRT14).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9804355", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Mutant keratins 5 or 14 are implicated in the etiology of epidermolysis bullosa simplex (EBS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9804355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22639907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22639907", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 137, "text": "Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26929861", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 99, "text": "Study of a family with epidermolysis bullosa simplex resulting from a novel mutation of KRT14 gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28777847", "endSection": "title" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1150, "text": "This is the first report of EBS-generalized intermediate in a newborn with de novo KRT5 gene mutation and KRT14 gene polymorphism, and no familial history of epidermolysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26929861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 461, "text": "Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in the keratin 5 (KRT5) and keratin 14 (KRT14) genes, with fragility of basal keratinocytes leading to epidermal cytolysis and blistering.In this study, we characterized mutations in KRT5 and KRT14 genes in patients with EBS and investigated their possible structure-function correlations.Mutations were characterized using polymerase chain reaction (PCR) and DNA sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20030639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Epidermolysis bullosa simplex (EBS) is a mechanobullous genodermatosis that may be caused by mutations in the genes KRT5 and KRT14 encoding the basal epidermal keratins 5 (K5) and 14 (K14).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21375516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Basal epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder resulting in most cases from missense mutations in the keratin 5 (KRT5) or keratin 14 (KRT14) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20199538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Epidermolysis bullosa simplex is a hereditary skin blistering disorder caused by mutations in the KRT5 or KRT14 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11407988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "BACKGROUND Basal epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder resulting in most cases from missense mutations in the keratin 5 (KRT5) or keratin 14 (KRT14) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20199538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Epidermolysis bullosa simplex is a group of blistering skin disorders caused by defects in one of the keratin genes, KRT5 and KRT14.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12655565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Epidermolysis bullosa simplex is an autosomal dominant inherited skin blistering disorder caused by mutations in the genes KRT5 or KRT14 coding for the basal epidermal keratins 5 and 14, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19797037", "endSection": "abstract" } ] }, { "body": "What biologic process in the body is associated with Mast cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15480318", "http://www.ncbi.nlm.nih.gov/pubmed/27619824", "http://www.ncbi.nlm.nih.gov/pubmed/16964309", "http://www.ncbi.nlm.nih.gov/pubmed/27288329", "http://www.ncbi.nlm.nih.gov/pubmed/11447391", "http://www.ncbi.nlm.nih.gov/pubmed/27381924", "http://www.ncbi.nlm.nih.gov/pubmed/9354811", "http://www.ncbi.nlm.nih.gov/pubmed/27302551", "http://www.ncbi.nlm.nih.gov/pubmed/24382176", "http://www.ncbi.nlm.nih.gov/pubmed/28439090", "http://www.ncbi.nlm.nih.gov/pubmed/17468237", "http://www.ncbi.nlm.nih.gov/pubmed/17386403", "http://www.ncbi.nlm.nih.gov/pubmed/6178551", "http://www.ncbi.nlm.nih.gov/pubmed/24342726", "http://www.ncbi.nlm.nih.gov/pubmed/16141514", "http://www.ncbi.nlm.nih.gov/pubmed/24903914", "http://www.ncbi.nlm.nih.gov/pubmed/9060446" ], "ideal_answer": [ "Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. ", "Mast cells are significantly involved in IgE-mediated allergic reactions but may be involved in defense against parasites as well as other immune mediated diseases including heart disease", "Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa" ], "exact_answer": [ "allergy" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D008407" ], "type": "factoid", "id": "5aac543bfcf4565872000004", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 125, "text": "Mast cells (MCs) may play an important role in plaque destabilization and atherosclerotic coronary complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27288329", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 84, "text": "Mast cells are significantly involved in IgE-mediated allergic reactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27302551", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 370, "text": " Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27619824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27381924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Mast cells are widely distributed throughout the body, predominantly near blood vessels and nerves, and express effector functions in allergic reactions, inflammatory diseases, and host defense.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16141514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The mast cell is the cellular basis for immediate hypersensitivity reactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6178551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Mast cells are important elements of the body response to foreign antigens, being those represented either by small molecules (allergic response) or harbored by foreign microorganisms (response to parasite infection).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17468237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Mast cells are ubiquitous in the body and multifunctional immune cells; they are known to be primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24382176", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 555, "text": "In IgE-associated biological responses, the crosslinking of FcεRI-bound IgE with multivalent antigens initiate the activation of mast cells by promoting aggregation of FceRI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24382176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Mast cell activation has been shown to be an initiator and a key determinant of foreign body reactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24342726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Mast cells are one of the major effector cells in the pathogenesis of the immediate-type hypersensitivity reaction in a number of non-allergic immune disorders as well as in normal physiological processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9060446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Mast cells act as sensors in innate immunity and as effector cells in adaptive immune reactions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28439090", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 128, "text": ": Allergic rhinitis is characterized by the epithelial accumulation of cells, particularly mast cells and eosinophils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15480318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Mast cells are important effector cells of the immune system and recent studies show that they have immunomodulatory roles in diverse processes in both health and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24903914", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1347, "text": "Biological functions of mast cells appear to include a role in innate immunity, involvement in host defense mechanisms against parasitic infestations, immunomodulation of the immune system, and tissue repair and angiogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9354811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Mast cells have long been known to play a detrimental role in the pathogenesis of IgE-associated allergic disorders by their ability to release a wide variety of pro-inflammatory mediators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17386403", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 106, "text": "Mast cells are long-lived resident cells that are of great importance in an allergic reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11447391", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 354, "text": "Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16964309", "endSection": "abstract" } ] }, { "body": "What are the 3 types of ultraviolet (UV) solar radiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24891049", "http://www.ncbi.nlm.nih.gov/pubmed/16117741", "http://www.ncbi.nlm.nih.gov/pubmed/23834148", "http://www.ncbi.nlm.nih.gov/pubmed/11100018" ], "ideal_answer": [ "Solar ultraviolet (UV) radiation, an ubiquitous environmental carcinogen, is classified depending on the wavelength, into three regions; short-wave UVC (200-280 nm), mid-wave UVB (280-320 nm), and long-wave UVA (320- 400 nm)", "short-wave UVC (200-280 nm), medium-wave UVB (280-320 nm), and long-wave UVA (320-400 nm).", "short-wave UVC (200-280 nm), medium-wave UVB (280-320 nm), and long-wave UVA (320-400 nm). " ], "exact_answer": [ [ "short wave UVC (200-280 nm)" ], [ "mid-wave UVB (280-320 nm)" ], [ "long-wave UVA (320- 400 nm)" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D012993", "https://meshb.nlm.nih.gov/record/ui?ui=D014466" ], "type": "list", "id": "5aae6a86fcf456587200000e", "snippets": [ { "offsetInBeginSection": 269, "offsetInEndSection": 359, "text": "short-wave UVC (200-280 nm), medium-wave UVB (280-320 nm), and long-wave UVA (320-400 nm).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16117741", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 224, "text": " short-wave UVC (200-280 nm), mid-wave UVB (280-320 nm), and long-wave UVA (320- 400 nm)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23834148", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 488, "text": "solar UV, largely confined to the UVB (290-320 nm) and short-wavelength UVA (320-340 nm) region, there is currently no agreed-upon method to measure broad-spectrum protection against long-wavelength UVA (340-400 nm).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11100018", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 235, "text": "Ultraviolet radiation is made up of UV-C, UV-B, and UV-A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24891049", "endSection": "abstract" } ] }, { "body": "Please list 10 conditions which play a role in causing atrial fibrillation.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25430048", "http://www.ncbi.nlm.nih.gov/pubmed/21072908", "http://www.ncbi.nlm.nih.gov/pubmed/14688506", "http://www.ncbi.nlm.nih.gov/pubmed/8149754", "http://www.ncbi.nlm.nih.gov/pubmed/28822529", "http://www.ncbi.nlm.nih.gov/pubmed/12001826", "http://www.ncbi.nlm.nih.gov/pubmed/19450312", "http://www.ncbi.nlm.nih.gov/pubmed/27247004", "http://www.ncbi.nlm.nih.gov/pubmed/11975840", "http://www.ncbi.nlm.nih.gov/pubmed/28496617", "http://www.ncbi.nlm.nih.gov/pubmed/2200378", "http://www.ncbi.nlm.nih.gov/pubmed/21718559", "http://www.ncbi.nlm.nih.gov/pubmed/3158290", "http://www.ncbi.nlm.nih.gov/pubmed/25994013", "http://www.ncbi.nlm.nih.gov/pubmed/19151857", "http://www.ncbi.nlm.nih.gov/pubmed/7846937", "http://www.ncbi.nlm.nih.gov/pubmed/22075545", "http://www.ncbi.nlm.nih.gov/pubmed/27957098", "http://www.ncbi.nlm.nih.gov/pubmed/12395441", "http://www.ncbi.nlm.nih.gov/pubmed/10535368", "http://www.ncbi.nlm.nih.gov/pubmed/10505494", "http://www.ncbi.nlm.nih.gov/pubmed/28496833", "http://www.ncbi.nlm.nih.gov/pubmed/19450316" ], "ideal_answer": [ "Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Multiple conditions like hypertension, heart failure, diabetes, sleep apnoea, hyperthyroidism and obesity play a role for the initiation and perpetuation of AF. Other possible causes are alcohol and drug use and atrial ischemia. Risk of AF increases with age." ], "exact_answer": [ [ "age" ], [ "heart disease" ], [ "Hypertension" ], [ "diabetes" ], [ "sleep apnea" ], [ "obesity" ], [ "GERD" ], [ "hyperthyroidism" ], [ "atrial ischemia" ], [ "drugs" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D001281", "http://www.disease-ontology.org/api/metadata/DOID:0050650", "https://meshb.nlm.nih.gov/record/ui?ui=D016275", "http://www.disease-ontology.org/api/metadata/DOID:0060224" ], "type": "list", "id": "5aaef38dfcf456587200000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Multiple conditions like hypertension, heart failure, diabetes, sleep apnoea, and obesity play a role for the initiation and perpetuation of AF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27247004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Atrial fibrillation is the most common arrhythmia worldwide with increasing frequency noted with age. Hyperthyroidism is a well-known cause of atrial fibrillation with a 16%-60% prevalence of atrial fibrillation in patients with known hyperthyroidism ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "Atrial fibrillation continues to be a challenging arrhythmia. There are some conventional, time-tested explanations of atrial fibrillation genesis, however some uncertainty of its complete understanding still exists. We focused on atrial ischemia which, hypothetically, could be responsible for manifestation of the arrhythmia, irrespective of the underlying heart disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28496833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The prevalence of atrial fibrillation (AF) increases with age. As the population ages, the burden of AF increases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28496617", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 800, "text": "t is estimated that this arrhythmia's suffers a significant increase throughout the entire life span, and that its highest raise occurs between the ages of 65 and 80. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21072908", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 305, "text": "Drug-induced tachyarrhythmias (ventricular tachycardia or atrial tachyarrhythmias with rapid ventricular response) are life-threatening and often cause syncope", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10505494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Atrial fibrillation is a growing health problem and the most common cardiac arrhythmia, affecting 5% of persons above the age of 65 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14688506", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 364, "text": "It occurs very often in patients with congestive heart failure and the prevalence increases with the severity of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14688506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "The prevalence and incidence of atrial fibrillation increase with age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11975840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Cardiac arrhythmias are a major problem in elderly persons, because of the high prevalence of underlying heart disease and hypertension,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12001826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Heavy alcohol use has been suspected to cause acute atrial fibrillation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3158290", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1074, "text": "Heavy alcohol use is an important potential etiology for acute atrial fibrillation; alcohol withdrawal may represent a particular risk for such alcohol-related atrial fibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3158290", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 360, "text": "Atrial fibrillation associated with rheumatic mitral valve disease has the highest stroke risk (about 17 times greater than unaffected controls), but even with nonvalvular heart disease, the risk is increased fivefold", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2200378", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 118, "text": "hronic atrial fibrillation is a very common arrhythmia affecting 2 to 4% of the population older than 60 years of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7846937", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1037, "text": "In western countries ischemic and hypertensive heart disease (including sick sinus syndrome) and alcohol (holiday heart syndrome) are numerically more important than the classical causes of atrial fibrillation--rheumatic heart disease and thyrotoxicosis-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7846937", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 142, "text": "Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450312", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 248, "text": " Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21718559", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 186, "text": "Diabetes mellitus is frequently accompanied by cardiac rhythm disorders. On the other hand, atrial fibrillation is the most frequent cardiac arrhythmia in adult population ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12395441", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 447, "text": "isk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430048", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 380, "text": " Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25994013", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 379, "text": "Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075545", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 378, "text": "Risk factors for atrial fibrillation include increasing age, coexisting cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and coexisting infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19450316", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 835, "text": "Thus, pericarditis might play a role in the development of recent atrial fibrillation during the course of myocardial infarction. Recent atrial fibrillation may be a sign of pericardial effusion which may be otherwise silent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8149754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Some patients develop atrial fibrillation after any type of surgery, some patients develop atrial fibrillation only after cardiac surgery, and still other patients never develop postoperative atrial fibrillation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10535368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Hypertension is known to increase the risk of atrial fibrillation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27957098", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 453, "text": "Of the long list of various cardiac conditions associated with an increased risk of cardioembolic strokes, non-valvular atrial fibrillation is the most common cause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19151857", "endSection": "abstract" } ] }, { "body": "Is p53 a transcription factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27990773", "http://www.ncbi.nlm.nih.gov/pubmed/28140789", "http://www.ncbi.nlm.nih.gov/pubmed/27216701" ], "ideal_answer": [ "Yes, p53 is a sequence-specific transcription factor." ], "exact_answer": "yes", "type": "yesno", "id": "5ac0817cd0c506ce46000001", "snippets": [ { "offsetInBeginSection": 64, "offsetInEndSection": 196, "text": "As a transcription factor, p53 mainly exerts its tumor suppressive function through transcriptional regulation of many target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27216701", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 326, "text": "p53 functions primarily as a sequence-specific transcription factor that controls the expression of hundreds of protein-coding genes and noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990773", "endSection": "abstract" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1036, "text": " p53 is a transcription factor ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28140789", "endSection": "abstract" } ] }, { "body": "Is Cystatin D a biomarker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28694499" ], "ideal_answer": [ "Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury" ], "exact_answer": "yes", "type": "yesno", "id": "5a9d9ab94e03427e73000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28694499", "endSection": "title" } ] }, { "body": "What causes leishmaniasis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28034363", "http://www.ncbi.nlm.nih.gov/pubmed/24105765", "http://www.ncbi.nlm.nih.gov/pubmed/25714343", "http://www.ncbi.nlm.nih.gov/pubmed/16477557", "http://www.ncbi.nlm.nih.gov/pubmed/24946952", "http://www.ncbi.nlm.nih.gov/pubmed/15259461", "http://www.ncbi.nlm.nih.gov/pubmed/20145708", "http://www.ncbi.nlm.nih.gov/pubmed/16436699", "http://www.ncbi.nlm.nih.gov/pubmed/25116660", "http://www.ncbi.nlm.nih.gov/pubmed/15071036", "http://www.ncbi.nlm.nih.gov/pubmed/24707415", "http://www.ncbi.nlm.nih.gov/pubmed/23219435", "http://www.ncbi.nlm.nih.gov/pubmed/29058760", "http://www.ncbi.nlm.nih.gov/pubmed/15135858", "http://www.ncbi.nlm.nih.gov/pubmed/25988048", "http://www.ncbi.nlm.nih.gov/pubmed/23868744", "http://www.ncbi.nlm.nih.gov/pubmed/23286822", "http://www.ncbi.nlm.nih.gov/pubmed/25228325", "http://www.ncbi.nlm.nih.gov/pubmed/11175518", "http://www.ncbi.nlm.nih.gov/pubmed/19002608", "http://www.ncbi.nlm.nih.gov/pubmed/26989711", "http://www.ncbi.nlm.nih.gov/pubmed/2670376", "http://www.ncbi.nlm.nih.gov/pubmed/24039881", "http://www.ncbi.nlm.nih.gov/pubmed/28903998" ], "ideal_answer": [ "Leishmania spp. is a group of very successful protozoan parasites that cause a range of diseases from self-healing cutaneous leishmaniasis to visceral leishmaniasis." ], "exact_answer": [ "Leishmania Species" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D016774", "https://meshb.nlm.nih.gov/record/ui?ui=D007897", "https://meshb.nlm.nih.gov/record/ui?ui=D007896", "https://meshb.nlm.nih.gov/record/ui?ui=D007898", "http://www.disease-ontology.org/api/metadata/DOID:9155", "http://www.disease-ontology.org/api/metadata/DOID:9065", "http://www.disease-ontology.org/api/metadata/DOID:9146", "http://www.disease-ontology.org/api/metadata/DOID:9111" ], "type": "factoid", "id": "5abcf0b0fcf4565872000024", "snippets": [ { "offsetInBeginSection": 466, "offsetInEndSection": 665, "text": "we will focus on the shape and form ofLeishmaniaspp., a group of very successful protozoan parasites that cause a range of diseases from self-healing cutaneous leishmaniasis to visceral leishmaniasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28903998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "In conclusion, our data demonstrates that in susceptible mice L. (L.) amazonensis, a causative agent of tegumentary leishmaniasis, causes pathological changes similar to those produced by Leishmania (L.) infantum in both humans and canids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15135858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "American Tegumentary Leishmaniasis is caused by parasites of the genus Leishmania, and causes significant health problems throughout the Americas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24039881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Leishmaniasis is a tropical infection caused by the protozoan, belonging to the group of Leishmania which causes Old World and New World disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24707415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25988048", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 408, "text": "Leishmania donovani is a causative agent of visceral leishmaniasis in South East Asia and Eastern Africa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23219435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa and associated with three main clinical presentations: cutaneous, mucocutaneous and visceral leishmaniasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23219435", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 614, "text": "L. (L.)\u00a0donovani usually causes visceral leishmaniasis, but in this case, the patient manifested cutaneous leishmaniasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Leishmania donovani in India causes visceral infection (kala-azar) and dermal infection (post-kala-azar dermal leishmaniasis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15071036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular protozoan parasites of the genus Leishmania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Leishmaniasis is a parasitic infection caused by many species of the protozoa Leishmania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2670376", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 491, "text": "Here we report an imported case of leishmaniasis by Leishmania (Leishmania) donovani infection from Sri Lanka.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228325", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 690, "text": "Finally, Leishmania species cause leishmaniasis, a disease that ranges from self-healing but scarring cutaneous lesions to fatal visceral leishmaniasis in which parasites disseminate to the liver, spleen, and bone marrow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24946952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25714343", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 748, "text": "In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25714343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Leishmania parasites cause leishmaniasis in humans and animals worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Leishmania is an intracellular protozoan parasite which causes Leishmaniasis, a global health problem affecting millions of people throughout 89 different countries in the world.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28034363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24105765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Leishmania major causes leishmaniasis and is grouped within the Trypanosomatidae family, which also includes the etiologic agent for African sleeping sickness, Trypanosoma brucei. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20145708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Leishmania major is an important trypanosomatid pathogen that causes leishmaniasis, which is a serious disease in much of the Old World.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16436699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Leishmania, a protozoan parasite that causes leishmaniasis, affects 1-2 million people every year worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The intracellular protozoan parasite Leishmania causes leishmaniasis, which is the second biggest killer worldwide among parasitic diseases, after malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19002608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The leishmaniases are a group of diseases caused by species of Leishmania and transmitted by the bite of the female sandfly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Sri Lankan cutaneous leishmaniasis is caused by Leishmania donovani zymodeme MON-37", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15259461", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 224, "text": "Tegumentary leishmaniasis in Latin America is caused mainly by Leishmania viannia braziliensis complex parasites. L. braziliensis and Leishmania viannia peruviana are the 2 predominant Leishmania species in Peru.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16477557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Identification of Leishmania species causing cutaneous leishmaniasis using Random Amplified Polymorphic DNA (RAPD-PCR) in Kharve, Iran.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26989711", "endSection": "title" } ] }, { "body": "Please list 7 classes of drugs that interact with Warfarin.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24038065", "http://www.ncbi.nlm.nih.gov/pubmed/17698824", "http://www.ncbi.nlm.nih.gov/pubmed/15911722", "http://www.ncbi.nlm.nih.gov/pubmed/18315779", "http://www.ncbi.nlm.nih.gov/pubmed/20095918", "http://www.ncbi.nlm.nih.gov/pubmed/17119104", "http://www.ncbi.nlm.nih.gov/pubmed/19934391", "http://www.ncbi.nlm.nih.gov/pubmed/23033232", "http://www.ncbi.nlm.nih.gov/pubmed/22198820", "http://www.ncbi.nlm.nih.gov/pubmed/23089199", "http://www.ncbi.nlm.nih.gov/pubmed/6347619", "http://www.ncbi.nlm.nih.gov/pubmed/8792056", "http://www.ncbi.nlm.nih.gov/pubmed/27416928", "http://www.ncbi.nlm.nih.gov/pubmed/8672833", "http://www.ncbi.nlm.nih.gov/pubmed/15585436", "http://www.ncbi.nlm.nih.gov/pubmed/21332566", "http://www.ncbi.nlm.nih.gov/pubmed/27365092", "http://www.ncbi.nlm.nih.gov/pubmed/23045839" ], "ideal_answer": [ "The number of drugs reported to interact with warfarin continues to expand. There are reports of interactions with azole antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake inhibitors, omeprazole, lipid-lowering agents, protease inhibitors, amiodarone, fluorouracil, psychotropics, and oral corticosteroids.", "Seven drugs/drug classes (ibuprofen, morphine, warfarin, bupropion, paroxetine, rosiglitazone, ACE inhibitors) with known ADEs were selected to evaluate the system. This study was aimed to determine the prevalence of drug-related problems (DRPs), identify the most common drugs, and drug classes involved in DRPs as well as associated factors with the occurrence of DRPs.A prospective cross-sectional study was conducted on 225 patients admitted to medical wards of Tikur Anbessa Specialized Hospital, Addis Ababa from March to June 2014. Analysis of the data showed that albumin possesses a single strong binding site for warfarin with an association constant of 154,000 at 3 degrees C and secondary classes of several sites with a much lower affinity. Four medications or medication classes were implicated alone or in combination in 67.0% (95% CI, 60.0 to 74.1) of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). Drugs such as gentamycin, warfarin, nifedipine, and cimetidine have the highest probability of causing DRP. Drugs with the highest drug risk ratio were gentamycin, warfarin, nifedipine, and cimetidine. The drugs most frequently causing a DRP were angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, diuretics, warfarin, spironolactone, and \u03b2-blockers." ], "exact_answer": [ [ "SSRI" ], [ "antibiotics" ], [ "NSAIDS" ], [ "antimetabolites" ], [ "oral corticosteroids" ], [ "protease inhibitors" ], [ "psychotropics" ], [ "statins/lipid lowering drugs" ], [ "omeprazole" ], [ "amiodarone" ], [ "carbamazapine" ], [ "narcotics/opiods" ], [ "cardiovascular drugs" ], [ "trazodone" ], [ "antifungals" ], [ "antivirals" ] ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D018565", "http://www.biosemantics.org/jochem#4250139", "https://meshb.nlm.nih.gov/record/ui?ui=D014859" ], "type": "list", "id": "5abce6acfcf4565872000022", "snippets": [ { "offsetInBeginSection": 1429, "offsetInEndSection": 1609, "text": "The combined use of warfarin and NSAIDs is generally discouraged because of the increased risk of bleeding in these patients. In patients receiving warfarin who also require NSAIDs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8672833", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1982, "text": "The number of drugs reported to interact with warfarin continues to expand. While most reports are of poor quality and present potentially misleading conclusions, the consistency of reports of interactions with azole antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake inhibitors, omeprazole, lipid-lowering agents, amiodarone, and fluorouracil, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15911722", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 126, "text": " potential drug interaction exists between oral corticosteroids and warfarin, but there is limited documentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119104", "endSection": "abstract" }, { "offsetInBeginSection": 1928, "offsetInEndSection": 2123, "text": "Use of oral corticosteroids in patients on long-term warfarin therapy may result in a clinically significant interaction, which requires close INR monitoring and possible warfarin dose reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119104", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 623, "text": "We review the possible mechanisms of this interaction and the reported interactions between warfarin and other protease inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17698824", "endSection": "abstract" }, { "offsetInBeginSection": 1859, "offsetInEndSection": 1965, "text": "It is necessary to intensify warfarin monitoring upon initiation or alteration of hormonal contraceptives.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19934391", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 204, "text": "To report a single patient case that presented with a probable drug interaction between warfarin and 3 methods of hormonal contraceptives, as assessed by the Horn Interaction Probability Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19934391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Warfarin-antibiotic interactions in older adults of an outpatient anticoagulation clinic", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23089199", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 235, "text": "Several classes of drugs, such as antibiotics, may interact with warfarin to cause an increase in warfarins anticoagulant activity and the clinical relevance of warfarin-antibiotic interactions in older adults is not clear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23089199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "As the number of psychotropics on the market expands, the likelihood increases that a patient requiring anticoagulation with warfarin will receive concurrent treatment with a psychotropic drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23033232", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1659, "text": "The most commonly identified potentially interacting medication pairs were warfarin and non-steroidal anti-inflammatory drugs (6824 cases), theophylline/aminophylline and ciprofloxacin/fluvoxamine (930), and warfarin and barbiturates (567).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18315779", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 927, "text": "Among 36 drugs that may interact with warfarin, fluconazole, amiodarone, and omeprazole were associated with the requirement for 45.8, 16.7, and 16.7% lower median warfarin dose (all P<0.05 with a false discovery rate <0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22198820", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1387, "text": "The results demonstrate a high prevalence of concomitant drug prescriptions with the potential for clinically relevant DDIs with warfarin, the most frequent being acetylsalicylic acid and amiodarone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27365092", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1105, "text": "We provide new support for the previous scarce evidence of interactions between warfarin and carbamazepine, bezafibrate, and lactulose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038065", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 733, "text": " Noteworthy are the interactions with cardiovascular or antilipidaemic drugs which are often coadministered with coumarins: amiodarone, propafenone and fibrates. Cardiovascular drugs which are obviously devoid or proven to be devoid of an interaction are angiotensin converting enzyme (ACE) inhibitors, calcium antagonists, beta-blockers and cardiac glycosides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8792056", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 826, "text": "Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23045839", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 1024, "text": "Isomeric differences in metabolism form an important basis for stereoselective metabolic interactions, especially inhibition; this has been demonstrated with phenylbutazone, metronidazole and co-trimoxazole", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6347619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Miconazole and nystatin used as topical antifungal drugs interact equally strongly with warfarin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21332566", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 179, "text": "A retrospective case series published in 2012 concluded that miconazole and nystatin used as topical antifungal drugs appear to interact equally strongly with warfarin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27416928", "endSection": "abstract" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1564, "text": " trazodone (2.2%) and carbamazepine (1.1%). The most commonly prescribed agents independently associated with increased bleeding risk were cyclooxygenase-2 inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15585436", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1371, "text": "Metabolic interaction between warfarin and antiretrovirals is likely, particularly if NNRTIs or PIs are included in the antiretroviral regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20095918", "endSection": "abstract" } ] }, { "body": "What part of the body is affected by mesotheliomia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28042777", "http://www.ncbi.nlm.nih.gov/pubmed/28007619", "http://www.ncbi.nlm.nih.gov/pubmed/27431778" ], "ideal_answer": [ "Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall.", "Malignant pleural mesothelioma (MPM) is a hard to treat malignancy arising from the mesothelial surface of the pleura. ", "Malignant pleural mesothelioma (MPM) is a hard to treat malignancy arising from the mesothelial surface of the pleura." ], "exact_answer": [ "lining of the lungs and chest wall" ], "type": "factoid", "id": "5a74eaa50384be955100000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Malignant pleural mesothelioma (MPM) is a hard to treat malignancy arising from the mesothelial surface of the pleura.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28042777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007619", "endSection": "abstract" } ] }, { "body": "What is BORSA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10834971", "http://www.ncbi.nlm.nih.gov/pubmed/2069374", "http://www.ncbi.nlm.nih.gov/pubmed/17108271", "http://www.ncbi.nlm.nih.gov/pubmed/28893360", "http://www.ncbi.nlm.nih.gov/pubmed/2261916", "http://www.ncbi.nlm.nih.gov/pubmed/25352679", "http://www.ncbi.nlm.nih.gov/pubmed/1563385", "http://www.ncbi.nlm.nih.gov/pubmed/18630132", "http://www.ncbi.nlm.nih.gov/pubmed/21875361", "http://www.ncbi.nlm.nih.gov/pubmed/18819540", "http://www.ncbi.nlm.nih.gov/pubmed/19116360", "http://www.ncbi.nlm.nih.gov/pubmed/20880412", "http://www.ncbi.nlm.nih.gov/pubmed/26679725" ], "ideal_answer": [ "Borderline oxacillin-resistant Staphylococcus aureus is also known as (BORSA)", "Borderline oxacillin-resistant Staphylococcus aureus (BORSA)", "Borderline oxacillin-resistant Staphylococcus aureus (BORSA). " ], "exact_answer": [ "Borderline oxacillin-resistant Staphylococcus aureus" ], "concepts": [ "https://meshb.nlm.nih.gov/record/ui?ui=D024881", "https://meshb.nlm.nih.gov/record/ui?ui=D024901", "https://meshb.nlm.nih.gov/record/ui?ui=D013211" ], "type": "factoid", "id": "5aae6499fcf456587200000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Borderline oxacillin-resistant Staphylococcus aureus (BORSA)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28893360", "endSection": "title" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1277, "text": "borderline oxacillin-resistant S. aureus (BORSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Borderline oxacillin-resistant Staphylococcus aureus (BORSA) may be misidentified as intrinsically methicillin-resistant Staphylococcus aureus (MRSA) in the clinical laboratory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1563385", "endSection": "abstract" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1455, "text": "Borderline oxacillin-resistant S. aureus (BORSA) isolates, shown to grow on plates containing 2 to 3 \u03bcg/mL of oxacillin, were found within S. aureus isolates from chicken (3 isolates) and from meat (19 isolates).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25352679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Since it is unknown whether \u03b2-lactam antimicrobial agents can be used effectively against borderline oxacillin-resistant Staphylococcus aureus (BORSA) with oxacillin MICs \u22654 mg/L, the in vitro bactericidal activity and pharmacodynamic effect of oxacillin against clinical BORSA isolates was evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20880412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a quite poorly understood and inadequately defined phenotype of methicillin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28893360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Borderline oxacillin-resistant Staphylococcus aureus (BORSA) exhibit oxacillin MIC values of 1-8 microg ml(-1), but lack mecA, which encodes the low-affinity penicillin-binding protein (PBP)2a.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17108271", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 331, "text": "Among them, 12 isolates were methicillin-susceptible S. aureus (MSSA), 18 were borderline-oxacillin-resistant S. aureus (BORSA), and 40 were methicillin-resistant S. aureus (MRSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21875361", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 658, "text": "hospital associated MRSA (HA-MRSA) and community associated MRSA (CA-MRSA), the presence of homogeneous and heterogeneous type of methicillin resistance, and border-line resistance in Staphylococcus aureus (BORSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18630132", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 746, "text": "borderline oxacillin resistant Staphylococcus aureus (BORSA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18819540", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 150, "text": "borderline oxacillin-resistant Staphylococcus aureus (BORSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19116360", "endSection": "abstract" }, { "offsetInBeginSection": 64, "offsetInEndSection": 151, "text": "borderline and heterotypic oxacillin-resistant Staphylococcus aureus (BORSA and ORSA) s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2069374", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 428, "text": "borderline oxacillin-resistant S. aureus (BORSA; mecA-negative, oxacillin MICs of 2 to 8 microgram/ml).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10834971", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 385, "text": "borderline oxacillin-resistant Staphylococcus aureus (BORSA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2261916", "endSection": "abstract" } ] }, { "body": "Which gene is responsible for proper speech development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15983371", "http://www.ncbi.nlm.nih.gov/pubmed/26980647", "http://www.ncbi.nlm.nih.gov/pubmed/25269856", "http://www.ncbi.nlm.nih.gov/pubmed/17033973", "http://www.ncbi.nlm.nih.gov/pubmed/12876151", "http://www.ncbi.nlm.nih.gov/pubmed/26212494", "http://www.ncbi.nlm.nih.gov/pubmed/21108403", "http://www.ncbi.nlm.nih.gov/pubmed/27148578" ], "ideal_answer": [ "Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech.", "The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation.", "The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.", "Transcription factor forkhead box protein p2 plays an essential role in the development of language and speech.The key regulator for language and speech development , foxp2 , is a novel substrate for sumoylation.", "The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation. Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech." ], "exact_answer": [ "FOXP2" ], "type": "factoid", "id": "5ace12be0340b9f058000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26212494", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26212494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17033973", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few cases have been described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17033973", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1237, "text": "Our results indicate that absence of paternal FOXP2 is the cause of DVD in patients with SRS with maternal UPD7. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17033973", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 533, "text": "Despite similarities in motor planning and execution between speech development and oral feeding competence, there have been no reports to date linking deletions within the FOXP2 gene to oral feeding impairments in the newborn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27148578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The gene responsible for the phenotype was mapped to chromosome 7q31 and identified as the FOXP2 gene, coding for a transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15983371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The discovery of the gene responsible, FOXP2, offers a unique opportunity to explore the relevant neural mechanisms from a molecular perspective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12876151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The FOXP2 gene is important for the development of proper speech motor control in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26980647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "BACKGROUND Mutations in the human FOXP2 gene cause speech and language impairments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269856", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 414, "text": "An adequate amount of functional FOXP2 protein is thought to be critical for the proper development of the neural circuitry underlying speech and language.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269856", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1338, "text": "CONCLUSIONS Our results reveal novel regulatory functions of the human FOXP2 3' UTR sequence and regulatory interactions between multiple miRNAs and the human FOXP2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269856", "endSection": "abstract" }, { "offsetInBeginSection": 1339, "offsetInEndSection": 1515, "text": "The expression of let-7a, miR-9, and miR-129-5p in the human fetal cerebellum is consistent with their roles in regulating FOXP2 expression during early cerebellum development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269856", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1410, "text": "CNTNAP2 is known to be involved in the cause of language and speech disorders and autism spectrum disorder and is in the same pathway as FOXP2, another important language gene, which makes it a candidate gene for causal studies speech and language disorders such as stuttering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21108403", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 403, "text": "An adequate amount of functional FOXP2 protein is thought to be critical for the proper development of the neural circuitry underlying speech and language.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25269856", "endSection": "abstract" } ] }, { "body": "What is PNPPP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26551787" ], "ideal_answer": [ "personally normalized plasma protein profiles (PNPPP)" ], "exact_answer": [ "personally normalized plasma protein profiles" ], "type": "factoid", "id": "5a9da59c4e03427e73000005", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 197, "text": " To study the impact of genetic and lifestyle factors on protein biomarkers and develop personally normalized plasma protein profiles (PNPPP) controlling for non-disease-related variance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26551787", "endSection": "abstract" } ] }, { "body": "What is Mendelian randomization?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26282889", "http://www.ncbi.nlm.nih.gov/pubmed/27846416" ], "ideal_answer": [ "Instrumental variable analysis is an approach for obtaining causal inferences on the effect of an exposure (risk factor) on an outcome from observational data. It has gained in popularity over the past decade with the use of genetic variants as instrumental variables, known as Mendelian randomization." ], "type": "summary", "id": "5a9da37e4e03427e73000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Instrumental variable analysis is an approach for obtaining causal inferences on the effect of an exposure (risk factor) on an outcome from observational data. It has gained in popularity over the past decade with the use of genetic variants as instrumental variables, known as Mendelian randomization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26282889", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 792, "text": "We use Mendelian randomization, with the genetic score as an instrumental variable (IV) for height to account for potential confounders that are related to socioeconomic background, early life conditions and parental investments, which are otherwise very difficult to fully account for when using covariates in observational studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27846416", "endSection": "abstract" } ] }, { "body": "What does the pembrolizumab companion diagnostic test assess?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28293123" ], "ideal_answer": [ "Administration of pembrolizumab requires a companion diagnostic test, to assess PD-L1 status of patients." ], "exact_answer": [ "PD-L1 status" ], "type": "factoid", "id": "5be48c39133db5eb7800001d", "snippets": [ { "offsetInBeginSection": 1139, "offsetInEndSection": 1303, "text": "The initial approval and subsequent studies of pembrolizumab required and utilized a companion diagnostic test, Dako's IHC 22C3, to assess PD-L1 status of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28293123", "endSection": "abstract" } ] }, { "body": "What is the combined effect of Nfat and miR-25?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24161931" ], "ideal_answer": [ "Increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium." ], "exact_answer": [ "Re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium." ], "type": "factoid", "id": "5c5f56501a4c55d80b00002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24161931", "endSection": "title" }, { "offsetInBeginSection": 185, "offsetInEndSection": 425, "text": "Here we report that increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24161931", "endSection": "abstract" } ] }, { "body": "In what states are GDF15 expression increased?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28081177", "http://www.ncbi.nlm.nih.gov/pubmed/28062617", "http://www.ncbi.nlm.nih.gov/pubmed/28025863", "http://www.ncbi.nlm.nih.gov/pubmed/27750354", "http://www.ncbi.nlm.nih.gov/pubmed/28159780" ], "ideal_answer": [ "Growth differentiation factor 15 (GDF-15) is expressed and secreted in response to inflammation, oxidative stress, hypoxia, telomere erosion, and oncogene activation." ], "exact_answer": [ [ "inflammation" ], [ "oxidative stress" ], [ "hypoxia" ], [ "telomere erosion" ], [ "oncogene activation" ], [ "tissue injury" ] ], "type": "list", "id": "5ad303970340b9f05800001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Macrophage inhibitory cytokine-1 (MIC-1), also known as growth differentiation factor 15 (GDF15), is a stress response cytokine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28081177", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 178, "text": "Growth differentiation factor 15 (GDF-15) is expressed and secreted in response to inflammation, oxidative stress, hypoxia, telomere erosion, and oncogene activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28062617", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 711, "text": "the tumour-derived macrophage inhibitory cytokine-1 (MIC-1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC-1 in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28025863", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 393, "text": "Growth differentiation factor-15, also known as macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the transforming growth factor- \u03b2 super family and increases during inflammatory states.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27750354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Growth differentiation factor-15 (GDF-15) is a member of the TGF-\u03b2cytokine superfamily that is widely expressed and may be induced in response to tissue injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28159780", "endSection": "abstract" } ] }, { "body": "Which genomic positions are preferentially selected for transposon insertion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9689229", "http://www.ncbi.nlm.nih.gov/pubmed/15947908", "http://www.ncbi.nlm.nih.gov/pubmed/12399934", "http://www.ncbi.nlm.nih.gov/pubmed/26818075", "http://www.ncbi.nlm.nih.gov/pubmed/16717285", "http://www.ncbi.nlm.nih.gov/pubmed/21276256" ], "ideal_answer": [ "Preferential integration occurs in non-coding DNA and heterochromatin. A preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was also observed." ], "exact_answer": [ "non coding DNA", "heterochromatin" ], "type": "factoid", "id": "5c34ad63da8336e21a000007", "snippets": [ { "offsetInBeginSection": 437, "offsetInEndSection": 617, "text": "These results suggest that in Drosophila preferential insertion sites may be defined with the contribution of host factors, although alternative interpretations are also possible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12399934", "endSection": "abstract" }, { "offsetInBeginSection": 1395, "offsetInEndSection": 1624, "text": "These data support the hypothesis that Tn916 has a marked preference for insertion into noncoding DNA for H. influenzae, suggesting that this mobile element has evolved to minimize disruption of host cell function on integration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9689229", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 479, "text": "Preferential integration points in the rye genome exist, because the new insertions seem to be located, in all studied cases, in the same genome positions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15947908", "endSection": "abstract" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1470, "text": "However, a similar approach did not reveal any structural pattern of DNA that could be used to predict favored integration sites for other transposons as well as retroviruses and lentiviruses due to a limitation of available data sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16717285", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1124, "text": "The FISH analysis of the pepper Tat elements showed a random distribution in heterochromatic and euchromatic regions, whereas the tomato Tat elements showed heterochromatin-preferential accumulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276256", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 879, "text": "No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was observed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26818075", "endSection": "abstract" } ] }, { "body": "Which Lisp framework has been developed for image processing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29106446" ], "ideal_answer": [ "FunImageJ is a Lisp framework for scientific image processing built upon the ImageJ software ecosystem. The framework provides a natural functional-style for programming, while accounting for the performance requirements necessary in big data processing commonly encountered in biological image analysis." ], "exact_answer": [ "FunImageJ" ], "type": "factoid", "id": "5c65b7657c78d6947100000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "FunImageJ: a Lisp framework for scientific image processing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29106446", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 313, "text": "FunImageJ is a Lisp framework for scientific image processing built upon the ImageJ software ecosystem. The framework provides a natural functional-style for programming, while accounting for the performance requirements necessary in big data processing commonly encountered in biological image analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29106446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Summary: FunImageJ is a Lisp framework for scientific image processing built upon the ImageJ software ecosystem.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29106446", "endSection": "abstract" } ] }, { "body": "Which gene controls the consistency of cerumen (ear wax)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25501636", "http://www.ncbi.nlm.nih.gov/pubmed/24572763" ], "ideal_answer": [ "A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent Our findings also reveal that ABCC11 genotype alone does not predict the type and relative levels of volatiles found in human cerumen, and suggest that other biochemical pathways must be involved", "A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent", "A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent ABCC11 encodes an ATP-driven efflux pump protein that plays an important function in ceruminous apocrine glands of the auditory canal and the secretion of axillary odor precursors.", "Recent studies link a single nucleotide polymorphism (SNP) in the adenosine triphosphate (ATP) binding cassette, sub-family C, member 11 gene (ABCC11) to the production of different types of axillary odorants and cerumen. ABCC11 encodes an ATP-driven efflux pump protein that plays an important function in ceruminous apocrine glands of the auditory canal and the secretion of axillary odor precursors." ], "exact_answer": [ "ABCC11" ], "type": "factoid", "id": "5acf74460340b9f058000013", "snippets": [ { "offsetInBeginSection": 215, "offsetInEndSection": 354, "text": "A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501636", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1064, "text": "Our findings also reveal that ABCC11 genotype alone does not predict the type and relative levels of volatiles found in human cerumen, and suggest that other biochemical pathways must be involved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25501636", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 517, "text": "ABCC11 encodes an ATP-driven efflux pump protein that plays an important function in ceruminous apocrine glands of the auditory canal and the secretion of axillary odor precursors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24572763", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 335, "text": "Recent studies link a single nucleotide polymorphism (SNP) in the adenosine triphosphate (ATP) binding cassette, sub-family C, member 11 gene (ABCC11) to the production of different types of axillary odorants and cerumen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24572763", "endSection": "abstract" } ] }, { "body": "What is the origin of human breast milk bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25398740" ], "ideal_answer": [ "It is believed that certain bacteria from the maternal gastrointestinal tract could translocate through a mechanism involving mononuclear immune cells, migrate to the mammary glands via an endogenous cellular route (the bacterial entero-mammary pathway), and subsequently colonize the gastrointestinal tract of the breast-fed neonate" ], "exact_answer": [ "Bacterial endero-mammary pathway" ], "type": "factoid", "id": "5be44ed3133db5eb78000016", "snippets": [ { "offsetInBeginSection": 183, "offsetInEndSection": 575, "text": "In the past years, results provided by different research groups suggest that certain bacteria from the maternal gastrointestinal tract could translocate through a mechanism involving mononuclear immune cells, migrate to the mammary glands via an endogenous cellular route (the bacterial entero-mammary pathway), and subsequently colonize the gastrointestinal tract of the breast-fed neonate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398740", "endSection": "abstract" } ] }, { "body": "Which species is the carrier of the SFTS ( severe fever with thrombocytopenia syndrome) virus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26957392", "http://www.ncbi.nlm.nih.gov/pubmed/24793967", "http://www.ncbi.nlm.nih.gov/pubmed/29665796", "http://www.ncbi.nlm.nih.gov/pubmed/25711611", "http://www.ncbi.nlm.nih.gov/pubmed/27495089" ], "ideal_answer": [ "The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in Haemaphysalis longicornis at all developmental stages. Tick-derived sequences shared over 95.6% identity with human- and animal-derived isolates. This study provides evidence that implicates ticks as not only vectors but also, reservoirs of SFTSV.", "Seroprevalence in animal species were: goats (66.8%), cattle (28.2%), dogs (7.4%), pigs (4.7%), chickens (1.2%), geese (1.7%), rodents (4.4%) and hedgehogs (2.7%). The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in H. longicornis at all developmental stages. Tick-derived sequences shared over 95.6% identity with human- and animal-derived isolates.", "The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in H. longicornis at all developmental stages. Severe fever with thrombocytopenia syndrome (SFTS) is a new emerging zoonosis." ], "exact_answer": [ "Haemaphysalis longicornis" ], "type": "factoid", "id": "5ad83cd6133db5eb78000010", "snippets": [ { "offsetInBeginSection": 1161, "offsetInEndSection": 1324, "text": "Seroprevalence in animal species were: goats (66.8%), cattle (28.2%), dogs (7.4%), pigs (4.7%), chickens (1.2%), geese (1.7%), rodents (4.4%) and hedgehogs (2.7%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24793967", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1156, "text": "The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in H. longicornis at all developmental stages. Tick-derived sequences shared over 95.6% identity with human- and animal-derived isolates. This study provides evidence that implicates ticks as not only vectors but also, reservoirs of SFTSV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25711611", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 90, "text": "Severe fever with thrombocytopenia syndrome (SFTS) is a new emerging zoonosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27495089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "A survey of reptile-associated ticks and their infection status with severe fever with thrombocytopenia syndrome (SFTS) virus was conducted to determine the relative abundance and distribution among lizards, skinks, and snakes in the Republic of Korea (ROK).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26957392", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 526, "text": "In total, 84 ixodid ticks belonging to two genera (Ixodes and Amblyomma) were collected from 28/132 (21.2%) lizards, skinks, and snakes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26957392", "endSection": "abstract" }, { "offsetInBeginSection": 1696, "offsetInEndSection": 1772, "text": "These results implicate lizards and snakes as potential hosts of SFTS virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26957392", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 230, "text": "Haemophysalis longicornis ticks have been considered the vector of severe fever with thrombocytopenia syndrome virus (SFTSV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29665796", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 927, "text": "The patient gradually recovered with treatments of corticosteroids and immunoglobulin.
CONCLUSION: These findings provide further evidence of SFTS viral transmission from H. longicornis to human.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29665796", "endSection": "abstract" } ] }, { "body": "List four features of the WHIM syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24523241", "http://www.ncbi.nlm.nih.gov/pubmed/19956569", "http://www.ncbi.nlm.nih.gov/pubmed/12692554", "http://www.ncbi.nlm.nih.gov/pubmed/29715199", "http://www.ncbi.nlm.nih.gov/pubmed/28928741", "http://www.ncbi.nlm.nih.gov/pubmed/29057173", "http://www.ncbi.nlm.nih.gov/pubmed/29066537", "http://www.ncbi.nlm.nih.gov/pubmed/28768817", "http://www.ncbi.nlm.nih.gov/pubmed/29659363", "http://www.ncbi.nlm.nih.gov/pubmed/21178277", "http://www.ncbi.nlm.nih.gov/pubmed/18274673", "http://www.ncbi.nlm.nih.gov/pubmed/21506920", "http://www.ncbi.nlm.nih.gov/pubmed/28512628", "http://www.ncbi.nlm.nih.gov/pubmed/23009155", "http://www.ncbi.nlm.nih.gov/pubmed/22596258", "http://www.ncbi.nlm.nih.gov/pubmed/22748845", "http://www.ncbi.nlm.nih.gov/pubmed/16899028", "http://www.ncbi.nlm.nih.gov/pubmed/14612668" ], "ideal_answer": [ "The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4." ], "exact_answer": [ [ "Warts" ], [ "Hypogammaglobulinemia" ], [ "Infections" ], [ "Myelokathexis" ] ], "type": "list", "id": "5c55de1607647bbc4b00000a", "snippets": [ { "offsetInBeginSection": 140, "offsetInEndSection": 565, "text": "To test whether there may be an advantage of one approach over the other for WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome - a primary immunodeficiency disorder caused by gain-of-function autosomal dominant mutations in chemokine receptor CXCR4 - we performed competitive transplantation experiments using both lethally irradiated WT (Cxcr4+/+) and unconditioned WHIM (Cxcr4+/w) recipient mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29715199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29659363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, which refers to abnormal accumulation of mature neutrophils in the bone marrow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28768817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28928741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28512628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a genetic disease characterized by neutropenia, lymphopenia, susceptibility to infections, and myelokathexis, which describes degenerative changes of mature neutrophils and hyperplasia of bone marrow myeloid cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29066537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "The WHIM syndrome features susceptibility to human Papillomavirus infection-induced warts and carcinomas, hypogammaglobulinemia, recurrent bacterial infections, B and T-cell lymphopenia, and neutropenia associated with retention of senescent neutrophils in the bone marrow (i.e.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21178277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "PURPOSE OF REVIEW: WHIM syndrome (the association of warts, hypogammaglobulinemia, recurrent bacterial infections, and 'myelokathexis') is a rare congenital form of neutropenia associated with an unusual immune disorder involving hypogammaglonulinemia and abnormal susceptibility to warts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14612668", "endSection": "abstract" } ] }, { "body": "Which algorithm has been developed for the automatic extraction of co-expressed gene clusters from gene expression data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30359297" ], "ideal_answer": [ "Clust is a method for automatic extraction of optimal co-expressed gene clusters from gene expression data. Clust is available at https://github.com/BaselAbujamous/clust." ], "exact_answer": [ "Clust" ], "type": "factoid", "id": "5c58474786df2b9174000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Clust: automatic extraction of optimal co-expressed gene clusters from gene expression data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359297", "endSection": "title" }, { "offsetInBeginSection": 367, "offsetInEndSection": 773, "text": "We present clust, a method that solves these problems by extracting clusters matching the biological expectations of co-expressed genes and outperforms widely used methods. Additionally, clust can simultaneously cluster multiple datasets, enabling users to leverage the large quantity of public expression data for novel comparative analysis. Clust is available at https://github.com/BaselAbujamous/clust .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359297", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 539, "text": "We present clust, a method that solves these problems by extracting clusters matching the biological expectations of co-expressed genes and outperforms widely used methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359297", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 709, "text": "Additionally, clust can simultaneously cluster multiple datasets, enabling users to leverage the large quantity of public expression data for novel comparative analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359297", "endSection": "abstract" } ] }, { "body": "Which bacteria are enriched in the gut microbiome of infants following exposure to fury pets?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28381231" ], "ideal_answer": [ "Pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus in infants." ], "exact_answer": [ [ "Oscillospira" ], [ "Ruminococcus" ] ], "type": "list", "id": "5be47df8133db5eb78000019", "snippets": [ { "offsetInBeginSection": 1315, "offsetInEndSection": 1522, "text": "As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P\u2009<\u20090.05) with more than a twofold greater likelihood of high abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28381231", "endSection": "abstract" }, { "offsetInBeginSection": 2111, "offsetInEndSection": 2359, "text": "The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28381231", "endSection": "abstract" } ] }, { "body": "List the main PPI databases.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27492077", "http://www.ncbi.nlm.nih.gov/pubmed/25622637", "http://www.ncbi.nlm.nih.gov/pubmed/10786290", "http://www.ncbi.nlm.nih.gov/pubmed/27980099", "http://www.ncbi.nlm.nih.gov/pubmed/17503393", "http://www.ncbi.nlm.nih.gov/pubmed/26228302", "http://www.ncbi.nlm.nih.gov/pubmed/15531608", "http://www.ncbi.nlm.nih.gov/pubmed/26620522" ], "ideal_answer": [ "PPIM,\nHPRD,\nSTRING,\nDAPID,\nMIPS,\nINTERACT,\nBioGRID" ], "exact_answer": [ [ "PPIM" ], [ "HPRD" ], [ "STRING" ], [ "DAPID" ], [ "MIPS" ], [ "INTERACT" ], [ "BioGRID" ] ], "type": "list", "id": "5ad4eddf133db5eb78000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "PPIM: A Protein-Protein Interaction Database for Maize.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26620522", "endSection": "title" }, { "offsetInBeginSection": 632, "offsetInEndSection": 721, "text": " experimentally validated human protein-protein interaction database, HPRD (interactome) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27492077", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 855, "text": "STRING Protein-Protein interaction database", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26228302", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 344, "text": "human protein-protein interaction database HPRD ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25622637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "DAPID: a 3D-domain annotated protein-protein interaction database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17503393", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 156, "text": "The MIPS mammalian protein-protein interaction database (MPPI) is a new resource of high-quality experimental protein interaction data in mammals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15531608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "INTERACT: an object oriented protein-protein interaction database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10786290", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 32, "text": "The BioGRID interaction database", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27980099", "endSection": "title" } ] }, { "body": "Is Baloxavir effective for influenza?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30395523", "http://www.ncbi.nlm.nih.gov/pubmed/30316915", "http://www.ncbi.nlm.nih.gov/pubmed/29623652", "http://www.ncbi.nlm.nih.gov/pubmed/30184455", "http://www.ncbi.nlm.nih.gov/pubmed/30476172", "http://www.ncbi.nlm.nih.gov/pubmed/30396860", "http://www.ncbi.nlm.nih.gov/pubmed/30203386", "http://www.ncbi.nlm.nih.gov/pubmed/29941893" ], "ideal_answer": [ "Yes. Baloxavir is approved for influenza A or B virus infections." ], "exact_answer": "yes", "type": "yesno", "id": "5c58a74e86df2b917400000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 358, "text": "Baloxavir marboxil (Xofluza\u2122; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. The drug blocks influenza virus proliferation by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 595, "text": "This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29941893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29941893", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30184455", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30184455", "endSection": "abstract" }, { "offsetInBeginSection": 1917, "offsetInEndSection": 2209, "text": "CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30184455", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 469, "text": "A single oral dose of baloxavir is usually well tolerated; it hastens alleviation of influenza symptoms and shortens the duration of viral shedding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30396860", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 156, "text": "Japan was the first country to approve baloxavir marboxil as a treatment for influenza.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30396860", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 599, "text": "This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 357, "text": "In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652", "endSection": "abstract" } ] }, { "body": "Which member of the human mycobiota is associated to atherosclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29124969" ], "ideal_answer": [ "Mucor racemosus is negatively associated with carotid atherosclerosis" ], "exact_answer": [ "Mucor racemosus" ], "type": "factoid", "id": "5be47fcb133db5eb7800001a", "snippets": [ { "offsetInBeginSection": 750, "offsetInEndSection": 856, "text": "Interestingly, the relative abundance of Mucor racemosus was negatively associated both with FRS and cIMT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124969", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1428, "text": "Variable importance in projection scores showed that M. racemosus abundance had the same impact in the model as waist-to-hip ratio, high-density lipoprotein-cholesterol, fasting triglycerides or fasting glucose, suggesting that M. racemosus relative abundance in the gut may be a relevant biomarker for cardiovascular risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124969", "endSection": "abstract" } ] }, { "body": "List intramembrane rhomboid peptidases", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12417197", "http://www.ncbi.nlm.nih.gov/pubmed/29301859", "http://www.ncbi.nlm.nih.gov/pubmed/22921757", "http://www.ncbi.nlm.nih.gov/pubmed/21455272" ], "ideal_answer": [ "PARL\nPcp1\nhiGlpG\necGlpG\nYqgP" ], "exact_answer": [ [ "PARL" ], [ "Pcp1" ], [ "hiGlpG" ], [ "ecGlpG" ], [ "YqgP" ] ], "type": "list", "id": "5c5f03371a4c55d80b000009", "snippets": [ { "offsetInBeginSection": 166, "offsetInEndSection": 189, "text": "rhomboid protease PARL ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29301859", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 814, "text": "The newly identified Pcp1 protein belongs to the rhomboid-GlpG superfamily of putative intramembrane peptidases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12417197", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 377, "text": "We subjected Haemophilus influenzae, (hiGlpG), Escherichia coli GlpG (ecGlpG) and Bacillus subtilis (YqgP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22921757", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 435, "text": "Crystal structures of H. influenzae (hiGlpG) and E. coli GlpG (ecGlpG) rhomboids have revealed a structure with six transmembrane helices and a Ser-His catalytic dyad buried within the membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21455272", "endSection": "abstract" } ] }, { "body": "Where is the protein Bouncer located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30190407", "http://www.ncbi.nlm.nih.gov/pubmed/11099133" ], "ideal_answer": [ "Bouncer is membrane bound." ], "exact_answer": [ "Bouncer is membrane bound." ], "type": "factoid", "id": "5c5f094c1a4c55d80b00000c", "snippets": [ { "offsetInBeginSection": 229, "offsetInEndSection": 252, "text": "Membrane-bound Bouncer ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30190407", "endSection": "abstract" } ] }, { "body": "How many genes in S. cerevisiae are the result of an ancient whole genome duplication?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16527865", "http://www.ncbi.nlm.nih.gov/pubmed/20820472", "http://www.ncbi.nlm.nih.gov/pubmed/17494770", "http://www.ncbi.nlm.nih.gov/pubmed/15004568", "http://www.ncbi.nlm.nih.gov/pubmed/17194778", "http://www.ncbi.nlm.nih.gov/pubmed/21546358" ], "ideal_answer": [ "The two genomes subsequently converged onto similar current sizes (5,600 protein-coding genes each) and independently retained sets of duplicated genes that are strikingly similar. Almost half of their surviving single-copy genes are not orthologs but paralogs formed by WGD, as would be expected if most gene pairs were resolved independently." ], "exact_answer": [ "2500" ], "type": "factoid", "id": "5c2f669e133db5eb78000031", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 516, "text": "By comparing three species (Saccharomyces cerevisiae, Candida glabrata, and S. castellii) that underwent WGD to a nonduplicated outgroup (Kluyveromyces lactis), and by using a synteny framework to establish orthology and paralogy relationships at each duplicated locus, we show that 56% of ohnolog pairs show significantly asymmetric protein sequence evolution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17194778", "endSection": "abstract" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1109, "text": "In particular, we analyze the evolution of WGD and non-WGD paralogs from the domain viewpoint, in comparison with a more standard functional analysis of the genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20820472", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 732, "text": " The two genomes subsequently converged onto similar current sizes (5,600 protein-coding genes each) and independently retained sets of duplicated genes that are strikingly similar. Almost half of their surviving single-copy genes are not orthologs but paralogs formed by WGD, as would be expected if most gene pairs were resolved independently.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17494770", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 651, "text": "The two genomes are related by a 1:2 mapping, with each region of K. waltii corresponding to two regions of S. cerevisiae, as expected for whole-genome duplication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15004568", "endSection": "abstract" } ] }, { "body": "Which intoxication is associated with Burton's line?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27803011", "http://www.ncbi.nlm.nih.gov/pubmed/24559541", "http://www.ncbi.nlm.nih.gov/pubmed/17179719" ], "ideal_answer": [ "Burton's line is characteristic for lead poisoning." ], "exact_answer": [ "lead" ], "type": "factoid", "id": "5c58962286df2b9174000007", "snippets": [ { "offsetInBeginSection": 476, "offsetInEndSection": 585, "text": "The patient's serum lead concentration was substantially elevated and he perhaps demonstrated Burton's line. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27803011", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1040, "text": "The second patient presented with abdominal pain and a Burton's line. The lead level was 52\u03bcg/dL and free erythrocyte protoporphyrin was 262\u03bcg/dL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24559541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 32, "text": "Burton's line in lead poisoning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17179719", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 486, "text": "This paper sketches the early history and remembers the important contribution of Henry Burton, who described the gums to be bordered by a narrow leaden-blue line, about the one-twentieth part of an inch in width, whilst the substance of the gum apparently retained its ordinary colour and condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17179719", "endSection": "abstract" } ] }, { "body": "Which tool has been developed for coverage calculation for genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29096012" ], "ideal_answer": [ "Mosdepth is a command-line tool for rapidly calculating genome-wide sequencing coverage. It measures depth from BAM or CRAM files at either each nucleotide position in a genome or for sets of genomic regions. Genomic regions may be specified as either a BED file to evaluate coverage across capture regions, or as a fixed-size window as required for copy-number calling. Mosdepth uses a simple algorithm that is computationally efficient and enables it to quickly produce coverage summaries.", "Mosdepth is a new command-line tool for rapidly calculating genome-wide sequencing coverage. It measures depth from BAM or CRAM files at either each nucleotide position in a genome or for sets of genomic regions." ], "exact_answer": [ "Mosdepth" ], "type": "factoid", "id": "5c59872b86df2b9174000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Mosdepth: quick coverage calculation for genomes and exomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29096012", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 749, "text": "Mosdepth is a new command-line tool for rapidly calculating genome-wide sequencing coverage. It measures depth from BAM or CRAM files at either each nucleotide position in a genome or for sets of genomic regions. Genomic regions may be specified as either a BED file to evaluate coverage across capture regions, or as a fixed-size window as required for copy-number calling. Mosdepth uses a simple algorithm that is computationally efficient and enables it to quickly produce coverage summaries. We demonstrate that mosdepth is faster than existing tools and provides flexibility in the types of coverage profiles produced.Availability and implementation: mosdepth is available from https://github.com/brentp/mosdepth under the MIT license.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29096012", "endSection": "abstract" } ] }, { "body": "Which type of sarcoma has been associated with members of the oral microbiome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26146997" ], "ideal_answer": [ "Alterations in the oral microbiota in the immunosuppressed population may be associated with diseases such as Kaposi's sarcoma." ], "exact_answer": [ "Kaposi's sarcoma" ], "type": "factoid", "id": "5be48987133db5eb7800001c", "snippets": [ { "offsetInBeginSection": 93, "offsetInEndSection": 495, "text": "Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26146997", "endSection": "abstract" } ] }, { "body": "Which complex is bound by estrogen-related receptor \u03b2 (Esrrb)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "http://www.ncbi.nlm.nih.gov/pubmed/23169531", "http://www.ncbi.nlm.nih.gov/pubmed/22143885", "http://www.ncbi.nlm.nih.gov/pubmed/24929238" ], "ideal_answer": [ "Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells.", "Knockdown of Mp1 redirected FGF4 signaling from differentiation toward pluripotency and up-regulated the pluripotency-related genes Esrrb, Rex1, Tcl1, and Sox2. Dax1 associates with Esrrb and regulates its function in embryonic stem cells. Here, we identified an orphan nuclear receptor, Esrrb (estrogen-related receptor beta), as a Dax1-interacting protein." ], "exact_answer": [ "The Esrrb-Sox2 complex" ], "type": "factoid", "id": "5c307474133db5eb78000033", "snippets": [ { "offsetInBeginSection": 846, "offsetInEndSection": 1006, "text": "Knockdown of Mp1 redirected FGF4 signaling from differentiation toward pluripotency and up-regulated the pluripotency-related genes Esrrb, Rex1, Tcl1, and Sox2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22143885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Dax1 associates with Esrrb and regulates its function in embryonic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "title" }, { "offsetInBeginSection": 252, "offsetInEndSection": 370, "text": "Here, we identified an orphan nuclear receptor, Esrrb (estrogen-related receptor beta), as a Dax1-interacting protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 982, "text": "Dax1 is a direct downstream target of Esrrb and that Esrrb can regulate Dax1 expression in an Oct3/4-independent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23508100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23169531", "endSection": "title" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1125, "text": "Through the use of knockdown experiments, we argue that the Esrrb-Sox2 complex is an arbiter of gene expression differences between ESCs and epiblast stem cells (EpiSC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23169531", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 746, "text": " Nanog expression in epiblast is directly regulated by Nodal/Smad2 pathway in a visceral endoderm-dependent manner. Notably, Nanog promoters switch from Oct4/Esrrb in ICM/ESCs to Oct4/Smad2 in epiblasts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24929238", "endSection": "abstract" } ] }, { "body": "Which approach was used to diagnose a patient with Cutis Verticis Gyrata-Intellectual Disability (CVG-ID) syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28019079" ], "ideal_answer": [ "Magnetic Resonance Imaging (MRI)" ], "exact_answer": [ "Magnetic Resonance Imaging", "MRI" ], "type": "factoid", "id": "5c632542e842deac6700000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 810, "text": "Cutis Verticis Gyrata-Intellectual Disability (CVG-ID) syndrome is a rare neurocutaneous syndrome characterized by intellectual disability and scalp folds and furrows that are typically absent at birth and are first noticed after puberty. First reported in 1893, the syndrome was mainly identified in subjects living in psychiatric institutions, where it was found to have a prevalence of up to 11.4%. Most patients were reported in the literature during the first half of the 20th century. CVG-ID is now a less reported and possibly under-recognized syndrome. Here, we report a patient with CVG-ID that was diagnosed using the novel approach of magnetic resonance imaging and we conduct a systematic review of all patients reported in the last 60 years, discussing the core clinical features of this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28019079", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 810, "text": "Here, we report a patient with CVG-ID that was diagnosed using the novel approach of magnetic resonance imaging and we conduct a systematic review of all patients reported in the last 60 years, discussing the core clinical features of this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28019079", "endSection": "abstract" } ] }, { "body": "Cemiplimab is used for treatment of which cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30456447", "http://www.ncbi.nlm.nih.gov/pubmed/30377167", "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "http://www.ncbi.nlm.nih.gov/pubmed/29934319" ], "ideal_answer": [ "Cemiplimab is a PD-1 inhibitor that is approved for treatment of metastatic or locally advanced cutaneous squamous cell carcinoma." ], "exact_answer": [ "cutaneous squamous cell carcinoma" ], "type": "factoid", "id": "5c58b99586df2b9174000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "endSection": "title" }, { "offsetInBeginSection": 283, "offsetInEndSection": 455, "text": " In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "endSection": "abstract" }, { "offsetInBeginSection": 1838, "offsetInEndSection": 2072, "text": "CONCLUSIONS: Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Cemiplimab Approved for Treatment of CSCC.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30377167", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The FDA greenlighted the PD-1 inhibitor cemiplimab to treat patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for surgery or radiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30377167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Cemiplimab Achieves Responses in Cutaneous Squamous Cell Carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934319", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "PD-1 blockade with cemiplimab has antitumor activity with adverse events similar to other PD-1 inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934319", "endSection": "abstract" }, { "offsetInBeginSection": 1626, "offsetInEndSection": 2112, "text": "Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.
CONCLUSIONS: Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The FDA greenlighted the PD-1 inhibitor cemiplimab to treat patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for surgery or radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30377167", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 773, "text": "In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.
METHODS: We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "endSection": "abstract" } ] }, { "body": "Which cancer has the kynureninase pathway been associated to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25415278" ], "ideal_answer": [ "The kynurenine pathway has been associated with human glioma pathophysiology." ], "exact_answer": [ "Glioma" ], "type": "factoid", "id": "5be494a0133db5eb7800001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Involvement of the kynurenine pathway in human glioma pathophysiology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25415278", "endSection": "title" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1902, "text": "These results provide further evidence for the involvement of the KP in glioma pathophysiology and highlight a potential role of KP products as novel and highly attractive therapeutic targets to evaluate for the treatment of brain tumors, aimed at restoring anti-tumor immunity and reducing the capacity for malignant cells to produce NAD(+), which is necessary for energy production and DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25415278", "endSection": "abstract" } ] }, { "body": "Which organs are mostly affected in Systemic Lupus Erythematosus (SLE)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25186992", "http://www.ncbi.nlm.nih.gov/pubmed/7588946", "http://www.ncbi.nlm.nih.gov/pubmed/19758166", "http://www.ncbi.nlm.nih.gov/pubmed/21767292", "http://www.ncbi.nlm.nih.gov/pubmed/28355987", "http://www.ncbi.nlm.nih.gov/pubmed/24268009" ], "ideal_answer": [ "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. The heart is one of the most frequently affected organs in SLE. Skin is one of the most commonly affected organs in SLE. Other affected organs in SLE-AAC included hematologic system (11, 84.6%), followed by mucocutaneous (seven, 53.8%), musculoskeletal (seven, 53.8%) and neuropsychiatric (two, 15.4%) systems.", "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. The heart is one of the most frequently affected organs in SLE. Skin is one of the most commonly affected organs in SLE", "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. The heart is one of the most frequently affected organs in SLE. Any part of the heart can be affected, including the pericardium, myocardium, coronary arteries, valves, and the conduction system", "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs." ], "exact_answer": [ [ "kidney" ], [ "brain" ], [ "heart" ], [ "skin" ] ], "type": "list", "id": "5c34a029da8336e21a000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7588946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The heart is one of the most frequently affected organs in SLE. Any part of the heart can be affected, including the pericardium, myocardium, coronary arteries, valves, and the conduction system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268009", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 221, "text": "Skin is one of the most commonly affected organs in SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25186992", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1244, "text": "Other affected organs in SLE-AAC included kidney (11, 84.6%) and hematologic system (11, 84.6%), followed by mucocutaneous (seven, 53.8%), musculoskeletal (seven, 53.8%) and neuropsychiatric (two, 15.4%) systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28355987", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 211, "text": "Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects multiple organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21767292", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 308, "text": "Cutaneous lupus erythematosus (CLE) includes skin symptoms seen in SLE and cutaneous-limited LE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21767292", "endSection": "abstract" } ] }, { "body": "What is a GPI anchor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29027702", "http://www.ncbi.nlm.nih.gov/pubmed/29393895", "http://www.ncbi.nlm.nih.gov/pubmed/29255114", "http://www.ncbi.nlm.nih.gov/pubmed/30094187" ], "ideal_answer": [ "Glycosylphosphatidylinositol (GPI) anchoring of proteins is a conserved posttranslational modification in the endoplasmic reticulum (ER). \tGlycosylphosphatidylinositols (GPIs) are lipid anchors allowing the exposure of proteins at the outer layer of the plasma membrane." ], "exact_answer": [ "Glycosylphosphatidylinositols (GPIs) are lipid anchors allowing the exposure of proteins at the outer layer of the plasma membrane." ], "type": "factoid", "id": "5c5f0fb41a4c55d80b000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Glycosylphosphatidylinositol (GPI) anchoring of proteins is a conserved posttranslational modification in the endoplasmic reticulum (ER). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "In eukaryotes, the glycosylphosphatidylinositol (GPI) modification of many glycoproteins on the cell surface is highly conserved. The lipid moieties of GPI-anchored proteins undergo remodelling processes during their maturation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29027702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Glycosylphosphatidylinositols (GPIs) are lipid anchors allowing the exposure of proteins at the outer layer of the plasma membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29393895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Glycosylphosphatidylinositol anchored proteins (GPI-APs) represent a class of soluble proteins attached to the external leaflet of the plasma membrane by a post-translation modification, the GPI anchor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30094187", "endSection": "abstract" } ] }, { "body": "In which way does DNA hydroxymethylation affect patients with Systemic Lupus Erythematosus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "http://www.ncbi.nlm.nih.gov/pubmed/29425851", "http://www.ncbi.nlm.nih.gov/pubmed/29113828", "http://www.ncbi.nlm.nih.gov/pubmed/23340289", "http://www.ncbi.nlm.nih.gov/pubmed/28752494" ], "ideal_answer": [ "DNA hydroxymethylation contributes to the aberrant regulation of genes transcription in the pathogenesis of SLE. A combined analysis of differential DNA hydroxymethylation profile and gene expression profile in SLE CD4(+) T cells, shows 131 genes with increased 5-hmC in promoter regions and up-regulated expression in SLE CD4(+) T cells compared with healthy controls, including selected immune-related genes, i.e. SOCS1, NR2F6 and IL15RA.", "Altered DNA methylation and hydroxymethylation as well as histone modifications mediate changes in chromatin accessibility and gene expression in immune cells from SLE patients. 5-Hydroxymethylcytosine (5-hmC) is a newly discovered modified form of cytosine suspected to be an important epigenetic modification in embryonic development, cell differentiation and cancer." ], "exact_answer": [ "gene activation" ], "type": "factoid", "id": "5c34ac49da8336e21a000006", "snippets": [ { "offsetInBeginSection": 321, "offsetInEndSection": 548, "text": "Our results showed that BDH2 expression was decreased, intracellular iron was increased, global DNA hydroxymethylation level was elevated, while methylation level was reduced in lupus CD4+ T cells compared with healthy controls", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113828", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 384, "text": "Altered DNA methylation and hydroxymethylation as well as histone modifications mediate changes in chromatin accessibility and gene expression in immune cells from SLE patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29425851", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 851, "text": "DNA hydroxymethylation was more recently identified as an activating epigenetic mark.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28752494", "endSection": "abstract" }, { "offsetInBeginSection": 986, "offsetInEndSection": 1178, "text": "On the other hand, certain miRNAs, RFX1, defective ERK pathway signaling, Gadd45\u03b1 and DNA hydroxymethylation have been proposed as potential mechanisms leading to DNA hypomethylation in lupus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23340289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Increased 5-hydroxymethylcytosine in CD4(+) T cells in systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 492, "text": " Indeed, there is increasing evidence that SLE is characterized by widespread epigenetic changes. 5-Hydroxymethylcytosine (5-hmC) is a newly discovered modified form of cytosine suspected to be an important epigenetic modification in embryonic development, cell differentiation and cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1672, "text": "Through a combined analysis of differential DNA hydroxymethylation profile and gene expression profile in SLE CD4(+) T cells, we found 131 genes with the increased 5-hmC in promoter regions and up-regulated expression in SLE CD4(+) T cells compared with healthy controls, including selected immune-related genes, i.e. SOCS1, NR2F6 and IL15RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" }, { "offsetInBeginSection": 1714, "offsetInEndSection": 1923, "text": "Furthermore, we demonstrate that CTCF, as a transcription factor, can mediate DNA hydroxymethylation and contribute to overexpression of SOCS1 in CD4(+) T cells through binding to the promoter region of SOCS1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" }, { "offsetInBeginSection": 2096, "offsetInEndSection": 2208, "text": "DNA hydroxymethylation contributes to the aberrant regulation of genes transcription in the pathogenesis of SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 314, "text": "Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113828", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 637, "text": "DNA methylation dynamics have already been implicated in the pathogenesis of SLE, while little is known about hydroxymethylation in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1077, "text": "Moreover, we present the differential patterns of DNA hydroxymethylation in genome-wide promoter regions in SLE CD4(+) T cells compared with healthy controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" }, { "offsetInBeginSection": 1331, "offsetInEndSection": 1648, "text": "Through a combined analysis of differential DNA hydroxymethylation profile and gene expression profile in SLE CD4(+) T cells, we found 131 genes with the increased 5-hmC in promoter regions and up-regulated expression in SLE CD4(+) T cells compared with healthy controls, including selected immune-related genes, i.e.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" }, { "offsetInBeginSection": 1924, "offsetInEndSection": 2208, "text": "Taken together, our study reveals a critical differential 5-hmC in the genome-wide promoter regions of SLE CD4(+) T cells and provides a novel mechanism that suggests that DNA hydroxymethylation contributes to the aberrant regulation of genes transcription in the pathogenesis of SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984631", "endSection": "abstract" } ] }, { "body": "What is the function of PAPOLA/PAP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21300291", "http://www.ncbi.nlm.nih.gov/pubmed/20174964", "http://www.ncbi.nlm.nih.gov/pubmed/15909992" ], "ideal_answer": [ "Poly(A)polymerase-alpha (PAPOLA) has been the most extensively investigated mammalian polyadenylating enzyme, mainly in regard to its multifaceted post-translational regulation. PolyA polymerase (PAP) adds a polyA tail onto the 3'-end of RNAs without a nucleic acid template, using adenosine-5'-triphosphate (ATP) as a substrate." ], "exact_answer": [ "PolyA polymerase (PAP) adds a polyA tail onto the 3'-end of RNAs without a nucleic acid template, using adenosine-5'-triphosphate (ATP) as a substrate." ], "type": "factoid", "id": "5c5f10791a4c55d80b000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Poly(A)polymerase-alpha (PAPOLA) has been the most extensively investigated mammalian polyadenylating enzyme, mainly in regard to its multifaceted post-translational regulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20174964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "PolyA polymerase (PAP) adds a polyA tail onto the 3'-end of RNAs without a nucleic acid template, using adenosine-5'-triphosphate (ATP) as a substrate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Polyadenylate polymerase (PAP) catalyzes the synthesis of 3'-polyadenylate tails onto mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15909992", "endSection": "abstract" } ] }, { "body": "List 3 diseases for which saRNAs have been evaluated as a potential treatment.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24489730", "http://www.ncbi.nlm.nih.gov/pubmed/28639200", "http://www.ncbi.nlm.nih.gov/pubmed/22872227" ], "ideal_answer": [ "saRNAs have been tested for the treatment of breast, bladder, liver cancer and more." ], "exact_answer": [ [ "Breast cancer" ], [ "Bladder cancer" ], [ "Liver cancer" ] ], "type": "list", "id": "5be94f3d133db5eb78000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Small activating RNA restores the activity of the tumor suppressor HIC-1 on breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24489730", "endSection": "title" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1373, "text": "Upon saRNA treatment, genes upregulated included those involved in immune activation, cell cycle interference, the induction of apoptosis, anti-metastasis, and cell differentiation. Downregulated genes included oncogenes and those that play roles in cell invasion, cell growth, and cell division.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24489730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder tumor model. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22872227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Treatment of Liver Cancer by C/EBPA saRNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28639200", "endSection": "title" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1485, "text": "In preclinical models of liver disease, treatment with C/EBP\u03b1 saRNA has shown reduction in tumor volume and improvement in serum markers of essential liver function such as albumin, bilirubin, aspartate aminotransferase (AST), and alanine transaminase (ALT). This saRNA that activates C/EBP\u03b1 for advanced HCC is the first saRNA therapy to have entered a human clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28639200", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Brigatinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29256901", "http://www.ncbi.nlm.nih.gov/pubmed/29174221", "http://www.ncbi.nlm.nih.gov/pubmed/28475456", "http://www.ncbi.nlm.nih.gov/pubmed/29119148", "http://www.ncbi.nlm.nih.gov/pubmed/30394941", "http://www.ncbi.nlm.nih.gov/pubmed/27780853", "http://www.ncbi.nlm.nih.gov/pubmed/29403310", "http://www.ncbi.nlm.nih.gov/pubmed/28435288", "http://www.ncbi.nlm.nih.gov/pubmed/29935304", "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "http://www.ncbi.nlm.nih.gov/pubmed/30251885", "http://www.ncbi.nlm.nih.gov/pubmed/30253203", "http://www.ncbi.nlm.nih.gov/pubmed/29856687", "http://www.ncbi.nlm.nih.gov/pubmed/29187012", "http://www.ncbi.nlm.nih.gov/pubmed/27144831", "http://www.ncbi.nlm.nih.gov/pubmed/28597393", "http://www.ncbi.nlm.nih.gov/pubmed/28536155", "http://www.ncbi.nlm.nih.gov/pubmed/29032042" ], "ideal_answer": [ "Brigatinib targets anaplastic lymphoma kinase. It is used for treatment of lung cancer (NSCLC)." ], "exact_answer": [ "anaplastic lymphoma kinase" ], "type": "factoid", "id": "5c588efb86df2b9174000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Molecular inhibitory mechanism study on the potent inhibitor brigatinib against four crizotinib-resistant ALK mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 688, "text": "As a potent and selective drug, brigatinib exhibits high efficacy against wild-type and mutant anaplastic lymphoma kinase (ALK) proteins to treat non-small cell lung cancer. In this work, the mechanisms of brigatinib binding to wild type and four mutant ALKs were investigated to gain insight into the dynamic energetic and structural information with respect to the design of novel inhibitors. Comparison between ALK-brigatinib and ALK-crizotinib suggests that the scaffold of brigatinib is well anchored to the residue Met1199 of hinge region by two hydrogen bonds, and the residue Lys1150 has the strong electrostatic interaction with the dimethylphosphine oxide moiety in brigatinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1248, "text": " Together, the detailed explanation of mechanisms of those mutations with brigatinib further provide several guidelines for the development of more effective ALK inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "PURPOSE OF REVIEW: We describe recent developments in the rapidly evolving field of anaplastic lymphoma kinase-targeting agents.RECENT FINDINGS: Five targeted drugs are currently available in the clinic via regular approval or named patient programs, including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394941", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1055, "text": " With the limit of a lower number of treated patients (n\u00a0= 359), brigatinib resulted as the most frequently involved in lung toxicity (7%; n\u00a0= 25).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29174221", "endSection": "abstract" }, { "offsetInBeginSection": 1505, "offsetInEndSection": 1647, "text": "Lung toxicity is a rare albeit potentially severe side effect in NSCLC patients receiving ALK-TKIs, apparently more frequent with brigatinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29174221", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1069, "text": "Ceritinib and alectinib are approved for metastatic ALK positive NSCLC patients, while brigatinib received granted accelerated approval by the United States Food and Drug Administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29187012", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 432, "text": "Since the discovery, development and approval of crizotinib in 2011, three second-generation ALK-TKIs, ceritinib, alectinib and brigatinib have been approved by the FDA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29256901", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 394, "text": "In this work, the mechanisms of brigatinib binding to wild type and four mutant ALKs were investigated to gain insight into the dynamic energetic and structural information with respect to the design of novel inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 687, "text": "Comparison between ALK-brigatinib and ALK-crizotinib suggests that the scaffold of brigatinib is well anchored to the residue Met1199 of hinge region by two hydrogen bonds, and the residue Lys1150 has the strong electrostatic interaction with the dimethylphosphine oxide moiety in brigatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 887, "text": "These ALK mutations have significant influences on the flexibility of P-loop region and DFG sequences, but do not impair the hydrogen bonds between brigatinib and the residue Met1199 of hinge region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "As a potent and selective drug, brigatinib exhibits high efficacy against wild-type and mutant anaplastic lymphoma kinase (ALK) proteins to treat non-small cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191596", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 515, "text": "This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144831", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 1020, "text": "Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144831", "endSection": "abstract" } ] }, { "body": "Which database associates human noncoding SNPs with their three-dimensional interacting genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27789693" ], "ideal_answer": [ "3DSNP is a database for linking human noncoding SNPs to their three-dimensional interacting genes. It a valuable resource for the annotation of human noncoding genome sequence and investigating the impact of noncoding variants on clinical phenotypes." ], "exact_answer": [ "3DSNP" ], "type": "factoid", "id": "5c532ad97e3cb0e23100001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "3DSNP: a database for linking human noncoding SNPs to their three-dimensional interacting genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789693", "endSection": "title" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1266, "text": "3DSNP is a valuable resource for the annotation of human noncoding genome sequence and investigating the impact of noncoding variants on clinical phenotypes. The 3DSNP database is available at http://biotech.bmi.ac.cn/3dsnp/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789693", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 703, "text": "Recent high-throughput chromosome conformation capture studies have outlined the principles of these elements interacting and regulating the expression of distal target genes through three-dimensional (3D) chromatin looping. Here we present 3DSNP, an integrated database for annotating human noncoding variants by exploring their roles in the distal interactions between genes and regulatory elements. 3DSNP integrates 3D chromatin interactions, local chromatin signatures in different cell types and linkage disequilibrium (LD) information from the 1000 Genomes Project.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789693", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 533, "text": "Here we present 3DSNP, an integrated database for annotating human noncoding variants by exploring their roles in the distal interactions between genes and regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789693", "endSection": "abstract" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1198, "text": "3DSNP is a valuable resource for the annotation of human noncoding genome sequence and investigating the impact of noncoding variants on clinical phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789693", "endSection": "abstract" } ] }, { "body": "In which phase of clinical trials was sutezolid in 2018?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25431273" ], "ideal_answer": [ "By 2018 sutezolid had been evaluated in phase II clinical trials." ], "exact_answer": [ "phase II" ], "type": "factoid", "id": "5c011057133db5eb78000025", "snippets": [ { "offsetInBeginSection": 283, "offsetInEndSection": 596, "text": "After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25431273", "endSection": "abstract" } ] }, { "body": "What is gingipain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29984580", "http://www.ncbi.nlm.nih.gov/pubmed/28726036", "http://www.ncbi.nlm.nih.gov/pubmed/28107612" ], "ideal_answer": [ "Porphyromonas gingivalis is a keystone periodontal pathogen that has been associated with autoimmune disorders. The cell surface proteases Lys-gingipain (Kgp) and Arg-gingipains (RgpA and RgpB) are major virulence factors, and their proteolytic activity is enhanced by small peptides such as glycylglycine (GlyGly)." ], "exact_answer": [ "A keystone periodontal pathogen. " ], "type": "factoid", "id": "5c5f2c0c1a4c55d80b000021", "snippets": [ { "offsetInBeginSection": 180, "offsetInEndSection": 250, "text": "y gingipains, a major proteinases produced by Porphyromonas gingivalis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28726036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Porphyromonas gingivalis is a keystone periodontal pathogen that has been associated with autoimmune disorders. The cell surface proteases Lys-gingipain (Kgp) and Arg-gingipains (RgpA and RgpB) are major virulence factors, and their proteolytic activity is enhanced by small peptides such as glycylglycine (GlyGly). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29984580", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 513, "text": "It also synthesizes several virulence factors, namely cysteine-proteases Arg- and Lys-gingipains ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28107612", "endSection": "abstract" } ] }, { "body": "For which disease is sutezolid developed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27280980" ], "ideal_answer": [ "Sutezolid is being developed as a treatment against tuberculosis." ], "exact_answer": [ "Tuberculosis" ], "type": "factoid", "id": "5c0112dd133db5eb78000026", "snippets": [ { "offsetInBeginSection": 534, "offsetInEndSection": 957, "text": "Various molecules, such as derivatives of fluoroquinolones (e.g. gatifloxacin, moxifloxacin and DC-159a), rifamycins (rifapentine), oxazolidinones (linezolid, sutezolid/PNU-100480), diarylquinolines (TMC207/bedaquiline), antifungal azoles, pyrrole (LL3858), nitroimidazopyran (PA824), nitroimidazole (OPC67683, TBA-354), diamine (SQ109) and benzothiazinone (BTZ043) are being developed in an attempt to combat the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27280980", "endSection": "abstract" } ] }, { "body": "What does gepotidacin do to bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28483959" ], "ideal_answer": [ "Gepotidacin inhibits bacterial DNA replication." ], "exact_answer": [ "Inhibits bacterial DNA replication" ], "type": "factoid", "id": "5c011448133db5eb78000027", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and hasin vitroactivity against susceptible and drug-resistant pathogens. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28483959", "endSection": "abstract" } ] }, { "body": "What is the role of fucokinase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12056818", "http://www.ncbi.nlm.nih.gov/pubmed/30503518" ], "ideal_answer": [ "FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases." ], "exact_answer": [ "The convertion of L-fucose to fucose-1-phosphate." ], "type": "factoid", "id": "5c5f3a1f1a4c55d80b000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30503518", "endSection": "abstract" }, { "offsetInBeginSection": 54, "offsetInEndSection": 187, "text": "L-Fucose kinase (fucokinase) takes part in the salvage pathway for reutilization of fucose from the degradation of oligosaccharides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12056818", "endSection": "abstract" } ] }, { "body": "Are there microbes in human breast milk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27940404" ], "ideal_answer": [ "Yes, human milk is a rich source of diverse bacteria." ], "exact_answer": "yes", "type": "yesno", "id": "5be44bef133db5eb78000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Contrary to long-held dogma, human milk is not sterile. Instead, it provides infants a rich source of diverse bacteria, particularly microbes belonging to the Staphylococcus, Streptococcus, and Pseudomonas genera.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940404", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 627, "text": "The origins of the bacteria in milk are thought to include the maternal gastrointestinal tract (via an entero-mammary pathway) and through bacterial exposure of the breast during nursing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940404", "endSection": "abstract" } ] }, { "body": "Is cariprazine effective for treatment of bipolar disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28843918", "http://www.ncbi.nlm.nih.gov/pubmed/24048386", "http://www.ncbi.nlm.nih.gov/pubmed/23361832", "http://www.ncbi.nlm.nih.gov/pubmed/27190727", "http://www.ncbi.nlm.nih.gov/pubmed/30323605", "http://www.ncbi.nlm.nih.gov/pubmed/27396597", "http://www.ncbi.nlm.nih.gov/pubmed/28343051", "http://www.ncbi.nlm.nih.gov/pubmed/27274384", "http://www.ncbi.nlm.nih.gov/pubmed/28478771", "http://www.ncbi.nlm.nih.gov/pubmed/27059102", "http://www.ncbi.nlm.nih.gov/pubmed/29017067", "http://www.ncbi.nlm.nih.gov/pubmed/26586950", "http://www.ncbi.nlm.nih.gov/pubmed/25562205", "http://www.ncbi.nlm.nih.gov/pubmed/23966785", "http://www.ncbi.nlm.nih.gov/pubmed/25056368", "http://www.ncbi.nlm.nih.gov/pubmed/30470662", "http://www.ncbi.nlm.nih.gov/pubmed/26510944", "http://www.ncbi.nlm.nih.gov/pubmed/29119668", "http://www.ncbi.nlm.nih.gov/pubmed/26655189", "http://www.ncbi.nlm.nih.gov/pubmed/30372510", "http://www.ncbi.nlm.nih.gov/pubmed/25532076" ], "ideal_answer": [ "Yes, cariprazine is effective for bipolar disorder." ], "exact_answer": "yes", "type": "yesno", "id": "5c61bacae842deac67000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: We evaluated the safety/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28843918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29017067", "endSection": "title" }, { "offsetInBeginSection": 110, "offsetInEndSection": 252, "text": "Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29017067", "endSection": "abstract" }, { "offsetInBeginSection": 1467, "offsetInEndSection": 1741, "text": "DISCUSSION: Cariprazine-treated patients with bipolar I disorder attained clinically significant improvement in manic symptoms as shown by significantly greater rates of response and remission versus placebo; improvement in manic symptoms did not induce depressive symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29017067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28478771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "BACKGROUND: Cariprazine was approved for treating schizophrenia and bipolar disorder, and currently is being evaluated for treating depression in clinical trials in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30372510", "endSection": "abstract" } ] }, { "body": "Is Bobble head doll syndrome associated with hydrocephalus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25878736", "http://www.ncbi.nlm.nih.gov/pubmed/29593205", "http://www.ncbi.nlm.nih.gov/pubmed/22886034", "http://www.ncbi.nlm.nih.gov/pubmed/24075844", "http://www.ncbi.nlm.nih.gov/pubmed/25506155", "http://www.ncbi.nlm.nih.gov/pubmed/29303456", "http://www.ncbi.nlm.nih.gov/pubmed/7674025" ], "ideal_answer": [ "Yes, Bobble head doll syndrome is associated with obstructive hydrocephalus." ], "exact_answer": "yes", "type": "yesno", "id": "5c55d75807647bbc4b000008", "snippets": [ { "offsetInBeginSection": 647, "offsetInEndSection": 788, "text": "The first is a 14-year-old boy with BHDS associated with aqueductal obstruction and triventricular hydrocephalus secondary to a tectal tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29303456", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 288, "text": "Brain magnetic resonance imaging showed a large suprasellar arachnoid cyst extending into the third ventricle, with obstructive hydrocephalus, characteristic of bobble-head doll syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29593205", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 619, "text": "MRI Scan showed a large contrast-enhanced lesion in the region of the third ventricle along with gross hydrocephalus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506155", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 479, "text": "Bobble-head doll syndrome is usually associated with dilation of the third ventricle, but is rarely associated with posterior fossa disease.PATIENT: We describe an infant with fetal hydrocephalus and an arachnoid cyst of the posterior fossa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075844", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 416, "text": "All the patients presented a psychomotor retardation due to an obstructive hydrocephalus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22886034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Suprasellar arachnoid cysts can have varied presentations with signs and symptoms of obstructive hydrocephalus, visual impairment, endocrinal dysfunction, gait ataxia and rarely bobble-head doll movement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25878736", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 592, "text": "We present three cases with bobble-head doll syndrome associated with a large suprasellar arachnoid cyst and obstructive hydrocephalus, which were treated with endoscopic cystoventriculocisternostomy and marsupialization of the cyst.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25878736", "endSection": "abstract" } ] }, { "body": "Can breastfeeding confer protection from type I diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21348815" ], "ideal_answer": [ "In the neonate and infant lactation confers protection from future type 1 diabetes." ], "exact_answer": "yes", "type": "yesno", "id": "5be44f50133db5eb78000017", "snippets": [ { "offsetInBeginSection": 310, "offsetInEndSection": 432, "text": "In the neonate and infant, among other benefits, lactation confers protection from future both type 1 and type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21348815", "endSection": "abstract" } ] }, { "body": "Can pets affect infant microbiomed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28381231" ], "ideal_answer": [ "Yes, exposure to household furry pets influences the gut microbiota of infants." ], "exact_answer": "yes", "type": "yesno", "id": "5be47bff133db5eb78000018", "snippets": [ { "offsetInBeginSection": 160, "offsetInEndSection": 359, "text": "Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28381231", "endSection": "abstract" }, { "offsetInBeginSection": 2111, "offsetInEndSection": 2359, "text": "The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28381231", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1949, "text": "As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P\u2009<\u20090.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P\u2009<\u20090.001, FDRp\u2009=\u20090.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06-0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16-0.58) for exposure in the pre- and postnatal time periods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28381231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Exposure to household furry pets influences the gut microbiota of infant at 3-4\u00a0months following various birth scenarios.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28381231", "endSection": "title" } ] }, { "body": "Is there any association between the human gut microbiome and depression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29016169" ], "ideal_answer": [ "Scientific findings are suggestive of the possibility that dysregulation of the enteric microbiota (i.e., dysbiosis) and associated bacterial translocation across the intestinal epithelium may be involved in the pathophysiology of stress-related psychiatric disorders, particularly depression." ], "exact_answer": "yes", "type": "yesno", "id": "5be48282133db5eb7800001b", "snippets": [ { "offsetInBeginSection": 335, "offsetInEndSection": 634, "text": "Moreover, recent findings are suggestive of the possibility that dysregulation of the enteric microbiota (i.e., dysbiosis) and associated bacterial translocation across the intestinal epithelium may be involved in the pathophysiology of stress-related psychiatric disorders, particularly depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29016169", "endSection": "abstract" } ] }, { "body": "Are whole-genome duplications more divergent than small-scale duplications in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19625390", "http://www.ncbi.nlm.nih.gov/pubmed/21079672", "http://www.ncbi.nlm.nih.gov/pubmed/17916239", "http://www.ncbi.nlm.nih.gov/pubmed/27799339", "http://www.ncbi.nlm.nih.gov/pubmed/23300483", "http://www.ncbi.nlm.nih.gov/pubmed/20525287" ], "ideal_answer": [ "Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts." ], "exact_answer": "yes", "type": "yesno", "id": "5c2f8127133db5eb78000032", "snippets": [ { "offsetInBeginSection": 759, "offsetInEndSection": 999, "text": " Also, we observe that transporter and glycolytic genes have a higher probability to be retained in duplicate after WGD and subsequent gene loss, both in the model as in S. cerevisiae, which leads to an increase in glycolytic flux after WGD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625390", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 758, "text": "We show that the retention of genes in duplicate in the model, corresponds nicely with those retained in duplicate after the ancestral WGD in S. cerevisiae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625390", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1455, "text": "Thus, our model confirms the hypothesis that WGD has been important in the adaptation of yeast to the new, glucose-rich environment that arose after the appearance of angiosperms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625390", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 708, "text": "Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17916239", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 709, "text": "The results uncover the WGD as a major source for the evolution of a complex interconnected block of transcriptional pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20525287", "endSection": "abstract" }, { "offsetInBeginSection": 1862, "offsetInEndSection": 2062, "text": "These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co-clustering into the same protein complexes, and share common interacting partners.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21079672", "endSection": "abstract" }, { "offsetInBeginSection": 1214, "offsetInEndSection": 1467, "text": "Moreover, we find additional transcriptional profiles that are suggestive of neo- and subfunctionalization of duplicate gene copies. These patterns are strongly correlated with the functional dependencies and sequence divergence profiles of gene copies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799339", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 235, "text": "Functional and transcriptional divergence between the copies after gene duplication has been considered the main driver of innovations .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799339", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 726, "text": "Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17916239", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 382, "text": "Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300483", "endSection": "abstract" } ] }, { "body": "Do yeast LTR give rise to circular DNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26681518", "http://www.ncbi.nlm.nih.gov/pubmed/22977178", "http://www.ncbi.nlm.nih.gov/pubmed/28090380", "http://www.ncbi.nlm.nih.gov/pubmed/26979517" ], "ideal_answer": [ "A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements. Circular retrotransposition products are generated by a LINE retrotransposon. Yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs). Circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence." ], "exact_answer": "yes", "type": "yesno", "id": "5c34794fda8336e21a000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Circular retrotransposition products generated by a LINE retrotransposon", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22977178", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons in Saccharomyces cerevisiae", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26681518", "endSection": "title" }, { "offsetInBeginSection": 128, "offsetInEndSection": 304, "text": "Ty eccDNA can arise from the circularization of extrachromosomal linear DNA during the transpositional life cycle of retrotransposons, or from circularization of genomic Ty DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26681518", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 478, "text": "Circularization may happen through nonhomologous end-joining (NHEJ) of long terminal repeats (LTRs) flanking Ty elements, by Ty autointegration, or by LTR-LTR recombination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26681518", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 255, "text": "We have recently shown that yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28090380", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 433, "text": "Similarly, circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28090380", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 514, "text": "A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26979517", "endSection": "abstract" } ] }, { "body": "Is cohesin linked to myeloid differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30127433" ], "ideal_answer": [ "Yes. There has been a link found between cohesin and myeloid differentiation which may help explain the prevalence of cohesin mutations in human acute myeloid leukemia." ], "exact_answer": "yes", "type": "yesno", "id": "5c644c3de842deac67000018", "snippets": [ { "offsetInBeginSection": 391, "offsetInEndSection": 895, "text": "Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30127433", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 673, "text": "Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30127433", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 899, "text": "These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30127433", "endSection": "abstract" } ] }, { "body": "Is pembrolizumab effective against Ewing's sarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28988646" ], "ideal_answer": [ "None of the 13 patients with Ewing's sarcoma receiving pembrolizumab had an objective response." ], "exact_answer": "no", "type": "yesno", "id": "5be49287133db5eb7800001e", "snippets": [ { "offsetInBeginSection": 2286, "offsetInEndSection": 2358, "text": "None of the 13 patients with Ewing's sarcoma had an objective response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28988646", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1741, "text": "Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28988646", "endSection": "abstract" } ] }, { "body": "Can gene therapy restore auditory function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28165476" ], "ideal_answer": [ "Yes, gene therapy can restore auditory function." ], "exact_answer": "yes", "type": "yesno", "id": "5be94b87133db5eb78000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28165476", "endSection": "title" }, { "offsetInBeginSection": 706, "offsetInEndSection": 1102, "text": "We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28165476", "endSection": "abstract" } ] }, { "body": "Is the PINES framework being used for the prediction of coding variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30359302" ], "ideal_answer": [ "No. PINES (Phenotype-Informed Noncoding Element Scoring) predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest." ], "exact_answer": "no", "type": "yesno", "id": "5c58447f07647bbc4b000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "PINES: phenotype-informed tissue weighting improves prediction of pathogenic noncoding variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359302", "endSection": "title" }, { "offsetInBeginSection": 126, "offsetInEndSection": 722, "text": "Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest. We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359302", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 356, "text": "Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359302", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 726, "text": "We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359302", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 498, "text": "PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359302", "endSection": "abstract" } ] }, { "body": "Is erythropoietin effective for treatment of amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25886781", "http://www.ncbi.nlm.nih.gov/pubmed/25595151" ], "ideal_answer": [ "No, erythropoietin is not effective for treatment of amyotrophic lateral sclerosis." ], "exact_answer": "no", "type": "yesno", "id": "5c647c52e842deac6700001c", "snippets": [ { "offsetInBeginSection": 545, "offsetInEndSection": 853, "text": "This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.METHODS: Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25886781", "endSection": "abstract" }, { "offsetInBeginSection": 1713, "offsetInEndSection": 1787, "text": "CONCLUSIONS: RhEPO 40,000\u2005IU fortnightly did not change the course of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25595151", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1602, "text": "At 12\u2005months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23\u2005h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25595151", "endSection": "abstract" } ] }, { "body": "Is celecoxib effective for treatment of amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16802291" ], "ideal_answer": [ "No. In clinical trial celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg/day in ALS were not recommended." ], "exact_answer": "no", "type": "yesno", "id": "5c6638717c78d69471000012", "snippets": [ { "offsetInBeginSection": 1197, "offsetInEndSection": 1488, "text": "NTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg/day in ALS are not warranted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1365, "text": "Prostaglandin E(2) levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment.
INTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" } ] }, { "body": "What is hemolacria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23040961", "http://www.ncbi.nlm.nih.gov/pubmed/21617906", "http://www.ncbi.nlm.nih.gov/pubmed/27879619", "http://www.ncbi.nlm.nih.gov/pubmed/23689678", "http://www.ncbi.nlm.nih.gov/pubmed/20224466" ], "ideal_answer": [ "Hemolacria is a rare phenomenon of bloody tears caused by various ocular and systemic conditions, as well as psychological, pharmacologic, and idiopathic etiologies." ], "type": "summary", "id": "5c5897c786df2b9174000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Hemolacria is a very rare entity which literally means \"bloody tears\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040961", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 561, "text": " In our case report, a 11-year-old female patient who presented with the complaint of bilateral epistaxis accompanied by bloody tears that had been present for 2 years and whose endoscopic examination revealed hyperemia and increased vascularity in the nasal cavity mucosa was discussed together with a review of the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "PURPOSE: Hemolacria is a rare phenomenon of bloody tears caused by various ocular and systemic conditions, as well as psychological, pharmacologic, and idiopathic etiologies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23689678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Hematidrosis (bloody sweat) and hemolacria (bloody tears) are very rare phenomena. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21617906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "PURPOSE: The purpose of this study was to report recurrent hemolacria, or \"bloody tears,\" as a sign of scleral buckle (SB) infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20224466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Bloody Epiphora (Hemolacria) Years After Repair of Orbital Floor Fracture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27879619", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 404, "text": "PURPOSE: The purpose of this study was to report recurrent hemolacria, or \"bloody tears,\" as a sign of scleral buckle (SB) infection.
METHODS: This is an interventional case series of three eyes of three patients with hemolacria after SB placement.
RESULTS: Two men and one woman were treated for recurrent hemolacria after SB placement for a rhegmatogenous retinal detachment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20224466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Hematidrosis (bloody sweat) and hemolacria (bloody tears) are very rare phenomena.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21617906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "PURPOSE: Hemolacria is a rare phenomenon of bloody tears caused by various ocular and systemic conditions, as well as psychological, pharmacologic, and idiopathic etiologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23689678", "endSection": "abstract" } ] }, { "body": "Are ultraconserved enhancers important for normal development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29358049" ], "ideal_answer": [ "Yes, ultraconserved enhancers are required for normal development." ], "exact_answer": "yes", "type": "yesno", "id": "5c531e887e3cb0e231000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Ultraconserved Enhancers Are Required for Normal Development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358049", "endSection": "title" }, { "offsetInBeginSection": 177, "offsetInEndSection": 403, "text": "However, initial deletion studies in mice revealed that loss of such extraordinarily constrained sequences had no immediate impact on viability. Here, we show that ultraconserved enhancers are required for normal development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358049", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 402, "text": "Here, we show that ultraconserved enhancers are required for normal development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358049", "endSection": "abstract" } ] }, { "body": "Is chlorotoxin a peptide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30486274", "http://www.ncbi.nlm.nih.gov/pubmed/28459137", "http://www.ncbi.nlm.nih.gov/pubmed/29495404", "http://www.ncbi.nlm.nih.gov/pubmed/28415833" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "type": "yesno", "id": "5c5f12d91a4c55d80b000016", "snippets": [ { "offsetInBeginSection": 721, "offsetInEndSection": 741, "text": "chlorotoxin peptide ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29495404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Chlorotoxin (CTX) is a 36-amino-acid disulfide-containing peptide derived from the venom of the scorpion Leiurus quinquestriatus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30486274", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 785, "text": "The mature Odontobuthus doriae chlorotoxin peptide has a 35-amino-acid residue and four disulfide bounds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28415833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Chlorotoxin (CTX), a disulfide-rich peptide from the scorpion Leiurus quinquestriatus,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459137", "endSection": "abstract" } ] }, { "body": "Does vesatolimod inhibit TLR7?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29104121" ], "ideal_answer": [ "No, vesatolimod is an agonist of toll-like receptor 7." ], "exact_answer": "no", "type": "yesno", "id": "5c00f38e133db5eb78000023", "snippets": [ { "offsetInBeginSection": 19, "offsetInEndSection": 139, "text": "Vesatolimod (GS-9620) is an oral agonist of toll-like receptor 7, an activator of innate and adaptive immune responses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104121", "endSection": "abstract" } ] }, { "body": "Is selenocysteine an aminoacid?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29447106", "http://www.ncbi.nlm.nih.gov/pubmed/29323455" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "type": "yesno", "id": "5c5f21a81a4c55d80b00001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Selenocysteine (Sec), a rare genetically encoded amino acid with unusual chemical properties, is of great interest for protein engineering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29447106", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 360, "text": "Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29323455", "endSection": "abstract" } ] }, { "body": "Is Tecovirimat effective for smallpox?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20393639", "http://www.ncbi.nlm.nih.gov/pubmed/25480757", "http://www.ncbi.nlm.nih.gov/pubmed/23530860", "http://www.ncbi.nlm.nih.gov/pubmed/30120738", "http://www.ncbi.nlm.nih.gov/pubmed/24100494", "http://www.ncbi.nlm.nih.gov/pubmed/29773767", "http://www.ncbi.nlm.nih.gov/pubmed/25896687", "http://www.ncbi.nlm.nih.gov/pubmed/29982575", "http://www.ncbi.nlm.nih.gov/pubmed/29972742" ], "ideal_answer": [ "Yes, tecovirimat FDA approved for treatment of smallpox." ], "exact_answer": "yes", "type": "yesno", "id": "5c58923c86df2b9174000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Oral Tecovirimat for the Treatment of Smallpox.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972742", "endSection": "title" }, { "offsetInBeginSection": 2001, "offsetInEndSection": 2206, "text": "CONCLUSIONS: On the basis of its efficacy in two animal models and pharmacokinetic and safety data in humans, tecovirimat is being advanced as a therapy for smallpox in accordance with the FDA Animal Rule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Background: Tecovirimat (ST-246) is being developed as an antiviral therapeutic for smallpox for use in the event of an accidental or intentional release. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29982575", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1384, "text": "Conclusions: Tecovirimat treatment initiated up to 8 days following a lethal aerosol MPXV challenge improves survival and, when initiated earlier than 5 days after challenge, provides protection from clinical effects of disease, supporting the conclusion that it is a promising smallpox antiviral therapeutic candidate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29982575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 35, "text": "Tecovirimat: First Global Approval.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30120738", "endSection": "title" }, { "offsetInBeginSection": 444, "offsetInEndSection": 618, "text": "In July 2018, oral tecovirimat was approved in the USA for the treatment of human smallpox disease caused by variola virus in adults and paediatric patients weighing \u2265\u00a013\u00a0kg.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30120738", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 873, "text": "An intravenous formulation of tecovirimat is undergoing phase I development for the treatment of smallpox infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30120738", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 1084, "text": "Brincidofovir, an oral antiviral in late stage development, has proven effective against orthopoxviruses in vitro and in vivo, has a different mechanism of action from tecovirimat (the only oral smallpox antiviral currently in the US Strategic National Stockpile), and has a resistance profile that reduces concerns in the scenario of a bioterror attack using genetically engineered smallpox.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29773767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25896687", "endSection": "title" }, { "offsetInBeginSection": 2035, "offsetInEndSection": 2216, "text": "Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24100494", "endSection": "abstract" } ] }, { "body": "Can simvastatin alleviate depressive symptoms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25827645" ], "ideal_answer": [ "Yes, simvastatin decreases depressive symptoms." ], "exact_answer": "yes", "type": "yesno", "id": "5c010e09133db5eb78000024", "snippets": [ { "offsetInBeginSection": 712, "offsetInEndSection": 1091, "text": "Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial (p=0.02). Early improvement and response rates were significantly greater in the simvastatin group than the placebo group (p=0.02 and p=0.01, respectively) but remission rate was not significantly different between the two groups (p=0.36).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827645", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1280, "text": "In conclusion, simvastatin seems to be a safe and effective adjuvant therapy for patients suffering from major depressive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25827645", "endSection": "abstract" } ] }, { "body": "Is P. gingivalis bacteria found in brain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28800332", "http://www.ncbi.nlm.nih.gov/pubmed/30281647" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "type": "yesno", "id": "5c5f2b771a4c55d80b000020", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 439, "text": "studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain is/are translocated to the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30281647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28800332", "endSection": "abstract" } ] }, { "body": "Is ibudilast effective for multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28258674", "http://www.ncbi.nlm.nih.gov/pubmed/30255442", "http://www.ncbi.nlm.nih.gov/pubmed/29779852", "http://www.ncbi.nlm.nih.gov/pubmed/29627873", "http://www.ncbi.nlm.nih.gov/pubmed/27521810", "http://www.ncbi.nlm.nih.gov/pubmed/30157388", "http://www.ncbi.nlm.nih.gov/pubmed/19929708", "http://www.ncbi.nlm.nih.gov/pubmed/27501293", "http://www.ncbi.nlm.nih.gov/pubmed/20200338", "http://www.ncbi.nlm.nih.gov/pubmed/15471363" ], "ideal_answer": [ "Yes, Ibudilast was shown to be effective for progressive multiple sclerosis. In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression." ], "exact_answer": "yes", "type": "yesno", "id": "5c58ac2286df2b917400000f", "snippets": [ { "offsetInBeginSection": 1155, "offsetInEndSection": 1244, "text": "Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29627873", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 312, "text": " Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30157388", "endSection": "abstract" }, { "offsetInBeginSection": 1631, "offsetInEndSection": 1894, "text": "CONCLUSIONS: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30157388", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1350, "text": "Specifically, the current evidence regarding treatment of progressive MS with ocrelizumab, simvastatin, ibudilast, alpha-lipoic acid, high-dose biotin, siponimod, and cell-based therapies are discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30255442", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 324, "text": "Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod\u2026); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin\u2026). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29779852", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1649, "text": "Current article provides an overview of the pharmacology of IBD with a focus on preclinical and clinical data supporting its potential neuroprotective benefits for neurological conditions, including multiple sclerosis, neuropathic pain, medication overuse headache, stroke, opioid, alcohol and methamphetamine abuse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28258674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521810", "endSection": "title" }, { "offsetInBeginSection": 681, "offsetInEndSection": 786, "text": "METHODS: SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521810", "endSection": "abstract" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1738, "text": "CONCLUSION: SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27521810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Ibudilast for the treatment of multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27501293", "endSection": "title" }, { "offsetInBeginSection": 593, "offsetInEndSection": 1065, "text": "AREAS COVERED: This article reviews various studies looking at ibudilast as a potential therapy for MS. It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology.EXPERT OPINION: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression. Ibudilast may have a role in the treatment of progressive MS phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27501293", "endSection": "abstract" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1934, "text": "Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.
CONCLUSIONS: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30157388", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 1021, "text": "It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology.
EXPERT OPINION: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27501293", "endSection": "abstract" } ] }, { "body": "Does gepotidacin activate bacterial topoisomerase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26586303" ], "ideal_answer": [ "No, gepotidacin is a bacterial topoisomerase inhibitor." ], "exact_answer": "no", "type": "yesno", "id": "5c0114ec133db5eb78000028", "snippets": [ { "offsetInBeginSection": 3, "offsetInEndSection": 116, "text": "GSK2140944 is a novel bacterial topoisomerase inhibitor in development for the treatment of bacterial infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586303", "endSection": "abstract" } ] }, { "body": "What is the 3D genome browser?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30286773", "http://www.ncbi.nlm.nih.gov/pubmed/25990738" ], "ideal_answer": [ "The 3D Genome Browser, http://3dgenome.org, allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types. The browser provides multiple methods linking distal cis-regulatory elements with their potential target genes. Users can seamlessly integrate thousands of other omics data to gain a comprehensive view of both regulatory landscape and 3D genome structure." ], "type": "summary", "id": "5c5207377e3cb0e231000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286773", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 653, "text": "Here, we introduce the 3D Genome Browser, http://3dgenome.org , which allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types. We design a new binary data format for Hi-C data that reduces the file size by at least a magnitude and allows users to visualize chromatin interactions over millions of base pairs within seconds. Our browser provides multiple methods linking distal cis-regulatory elements with their potential target genes. Users can seamlessly integrate thousands of other omics data to gain a comprehensive view of both regulatory landscape and 3D genome structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286773", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 442, "text": "We introduce simultaneously a database system to store and query 3D genomic data (3DBG), and a 3D genome browser to visualize and explore 3D genome structures (3DGB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25990738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Here, we introduce the 3D Genome Browser, http://3dgenome.org , which allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286773", "endSection": "abstract" } ] }, { "body": "Are gut proteobacteria associated with inflammatory disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26764594", "http://www.ncbi.nlm.nih.gov/pubmed/26749064", "http://www.ncbi.nlm.nih.gov/pubmed/26574491", "http://www.ncbi.nlm.nih.gov/pubmed/28842640", "http://www.ncbi.nlm.nih.gov/pubmed/25018784", "http://www.ncbi.nlm.nih.gov/pubmed/24668769" ], "ideal_answer": [ "The onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear." ], "type": "summary", "id": "5ad3130c0340b9f05800001d", "snippets": [ { "offsetInBeginSection": 642, "offsetInEndSection": 751, "text": "In the IBD group, Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria were significantly increased,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28842640", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1094, "text": "Bacterial microbiota in Crohn's disease patients was characterised by a restriction in biodiversity. with an increase of Proteobacteria and Fusobacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26574491", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 299, "text": "the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26764594", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1384, "text": "Similar to the findings in inflammatory disease states, SSc patients had decreased levels of commensal bacteria, such as Faecalibacterium and Clostridium, and increased levels of pathobiont bacteria, such as Fusobacterium and \u03b3-Proteobacteria, compared with healthy controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26749064", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1074, "text": " The colonic and cecal microbiota of healthy mice fed \u03b1-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24668769", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1140, "text": "Significant increase in abundance of unusual aerobes and facultative anaerobes, including members from the phylum Proteobacteria (p-\u2009=\u20090.031) was also observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25018784", "endSection": "abstract" } ] }, { "body": "What brain procedure can be done using the NeuroBlate system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28188403", "http://www.ncbi.nlm.nih.gov/pubmed/27838155", "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "http://www.ncbi.nlm.nih.gov/pubmed/24471476", "http://www.ncbi.nlm.nih.gov/pubmed/28348940", "http://www.ncbi.nlm.nih.gov/pubmed/29328005", "http://www.ncbi.nlm.nih.gov/pubmed/28411414", "http://www.ncbi.nlm.nih.gov/pubmed/24810945" ], "ideal_answer": [ "NeuroBlate System is used for Laser interstitial thermal therapy." ], "exact_answer": [ "Laser interstitial thermal therapy" ], "type": "factoid", "id": "5c588d0986df2b9174000003", "snippets": [ { "offsetInBeginSection": 435, "offsetInEndSection": 604, "text": " At 3 years of age, he underwent stereotactic laser ablation with an aim of disconnection of the lesion. The procedure was performed with the NeuroBlate SideFire probe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29328005", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 453, "text": "The authors perform a systematic analysis of two commercially available MRgLITT systems used in neurosurgery: the Visualase\u00ae thermal therapy and NeuroBlate\u00ae Systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27838155", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 564, "text": "We describe the history and rationale of laser neurosurgery as well as the two available SLT systems (Visualase\u00ae and NeuroBlate\u00ae; CE marks pending). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28188403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 514, "text": "INTRODUCTION: We describe the feasibility of using minimally invasive robotic laser interstitial thermotherapy (LITT) for achieving an anterior two-thirds\u00a0as well as a complete corpus callosotomy.METHODS: Ten probe trajectories were plotted on normal magentic resonance imaging (MRI) scans using the Brainlab Stereotactic Planning Software (Brainlab, Munich, Germany). The NeuroBlate\u00ae System (Monteris Medical, MN, USA) was used to conform the thermal burn to the corpus callosum along the trajectory of the probe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28348940", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 849, "text": "Here, we briefly describe the history and rationale of laser neurosurgery as well as the technical key features of the two currently available systems for magnetic resonance-guided LiTT (Visualase\u00ae, NeuroBlate\u00ae; CE marks pending for both).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28411414", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 594, "text": "We report our multicenter results of laser interstitial thermal therapy (LITT) in DTA-HGGs. We retrospectively reviewed 34 consecutive DTA-HGG patients (24 glioblastoma, 10 anaplastic) who underwent LITT at Cleveland Clinic, Washington University, and Wake Forest University (May 2011-December 2012) using the NeuroBlate(\u00ae) System. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24810945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Laser interstitial thermal therapy in treatment of brain tumors--the NeuroBlate System.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24471476", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "OBJECT: Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" }, { "offsetInBeginSection": 1755, "offsetInEndSection": 1982, "text": "Three had Grade 3 adverse events at the highest dose.
CONCLUSIONS: NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560574", "endSection": "abstract" } ] }, { "body": "Describe genomiser", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27569544" ], "ideal_answer": [ "Genomiser is an analysis framework that is able not only to score the relevance of variation in the non-coding genome, but also to associate regulatory variants to specific Mendelian diseases. Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to discover variants associated to specific Mendelian disorders. Genomiser is able to identify causal regulatory variants as the top candidate in 77% of simulated whole genomes, allowing effective detection and discovery of regulatory variants in Mendelian disease." ], "type": "summary", "id": "5c522b487e3cb0e231000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 927, "text": "The interpretation of non-coding variants still constitutes a major challenge in the application of whole-genome sequencing in Mendelian disease, especially for single-nucleotide and other small non-coding variants. Here we present Genomiser, an analysis framework that is able not only to score the relevance of variation in the non-coding genome, but also to associate regulatory variants to specific Mendelian diseases. Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to\u00a0discover variants associated to specific Mendelian disorders. Overall, Genomiser is able to identify causal regulatory variants as the\u00a0top candidate in 77% of simulated whole genomes, allowing effective detection and discovery of regulatory variants in Mendelian disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 422, "text": "Here we present Genomiser, an analysis framework that is able not only to score the relevance of variation in the non-coding genome, but also to associate regulatory variants to specific Mendelian diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 717, "text": "Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to\u00a0discover variants associated to specific Mendelian disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27569544", "endSection": "abstract" } ] }, { "body": "Which ultraconserved element is associated with Embryonic Stem Cells (ESC) self-renewal?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29456181" ], "ideal_answer": [ "Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed and represent a new family of long non-coding RNAs (lncRNAs), the transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the physiological role of T-UCEs is still unknown. A lncRNA containing the uc.170+, named T-UCstem1, was identified with in vitro and in vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics." ], "exact_answer": [ "T-UCstem1" ], "type": "factoid", "id": "5c580aff07647bbc4b00001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "An Ultraconserved Element Containing lncRNA Preserves Transcriptional Dynamics and Maintains ESC Self-Renewal.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29456181", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 605, "text": "Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed and represent a new family of long non-coding RNAs (lncRNAs), the transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the physiological role of T-UCEs is still unknown. Here, we identify a lncRNA containing the uc.170+, named T-UCstem1, and provide in\u00a0vitro and in\u00a0vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29456181", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 605, "text": "Here, we identify a lncRNA containing the uc.170+, named T-UCstem1, and provide in\u00a0vitro and in\u00a0vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29456181", "endSection": "abstract" } ] }, { "body": "What is TPMCalculator?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30379987" ], "ideal_answer": [ "The quantification of RNA sequencing (RNA-seq) abundance using a normalization method that calculates transcripts per million (TPM) is a key step to compare multiple samples from different experiments. TPMCalculator is a one-step software to process RNA-seq alignments in BAM format and reports TPM values, raw read counts and feature lengths for genes, transcripts, exons and introns. The program describes the genomic features through a model generated from the gene transfer format (GTF) file used during alignments reporting of the TPM values and the raw read counts for each feature." ], "type": "summary", "id": "5c5824cf07647bbc4b00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "TPMCalculator: one-step software to quantify mRNA abundance of genomic features.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30379987", "endSection": "title" }, { "offsetInBeginSection": 8, "offsetInEndSection": 597, "text": " The quantification of RNA sequencing (RNA-seq) abundance using a normalization method that calculates transcripts per million (TPM) is a key step to compare multiple samples from different experiments. TPMCalculator is a one-step software to process RNA-seq alignments in BAM format and reports TPM values, raw read counts and feature lengths for genes, transcripts, exons and introns. The program describes the genomic features through a model generated from the gene transfer format (GTF) file used during alignments reporting of the TPM values and the raw read counts for each feature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30379987", "endSection": "abstract" } ] }, { "body": "Describe clinical presentation of Escobar syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9436410", "http://www.ncbi.nlm.nih.gov/pubmed/12479430", "http://www.ncbi.nlm.nih.gov/pubmed/16826520", "http://www.ncbi.nlm.nih.gov/pubmed/25365855", "http://www.ncbi.nlm.nih.gov/pubmed/25411939", "http://www.ncbi.nlm.nih.gov/pubmed/25196531", "http://www.ncbi.nlm.nih.gov/pubmed/25219146", "http://www.ncbi.nlm.nih.gov/pubmed/24472885", "http://www.ncbi.nlm.nih.gov/pubmed/25610221", "http://www.ncbi.nlm.nih.gov/pubmed/30461311", "http://www.ncbi.nlm.nih.gov/pubmed/18751807", "http://www.ncbi.nlm.nih.gov/pubmed/27902173" ], "ideal_answer": [ "The Escobar variant of multiple pterygium syndrome (MPS) is a rare, autosomal recessive disorder which is characterized by pterygia, arthrogryposis (joint contractures), facial dysmorphism along with other anomalies." ], "type": "summary", "id": "5c5866c086df2b9174000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "BACKGROUND: Escobar syndrome, a nonlethal variant of multiple pterygium syndromes (MPS), is a rare autosomal recessive disorder characterized by pterygia and multiple joint contractures along with other anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30461311", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 378, "text": "It is generally characterized by multiple pterygia that are found in the cervical, antecubital and popliteal regions. In this report, we present the treatment management of a 14-year-old case with late stage Escobar syndrome who was admitted due to multiple pterygia and bilateral knee contractures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27902173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Escobar syndrome is a nonlethal subtype of multiple pterygium syndromes, characterized by webbing across the joints, congenital joint contracture, facial dysmorphism and a variety of other congenital anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25411939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 541, "text": "The Escobar variant of multiple pterygium syndrome (MPS) is a rare, autosomal recessive disorder which may lead to many serious or even lethal fetal abnormalities. MPS is characterized by pterygia, arthrogryposis (joint contractures), and intrauterine growth restriction (IUGR). In the case described below, increased fetal nuchal translucency was the first abnormality diagnosed already in the first trimester of pregnancy. Other symptoms of the disease were found during the second trimester of pregnancy using ultrasonography examination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25219146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Nonlethal multiple pterygium syndrome: Escobar syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24472885", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Escobar syndrome (ES) or multiple pterygia syndrome (MIM#265000) is an infrequent condition characterized by facial dysmorphism, multiple webbing (pterygia), congenital contractures (arthrogryposis) and other internal anomalies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25365855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Escobar syndrome is characterized with multiple pterygia or webs of the skin and multiple congenital anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25196531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Nonlethal Escobar is a rare disorder that is a variant of multiple pterygium syndromes. It is a form of arthrogryposis multiplex congenita characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24472885", "endSection": "abstract" } ] }, { "body": "What is small-activating RNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26401871" ], "ideal_answer": [ "small activating RNAs are double stranded RNAs (dsRNAs) that target gene promoters and trigger gene activation." ], "type": "summary", "id": "5be94c90133db5eb78000021", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 179, "text": "RNA activation (RNAa) is a mechanism of gene activation triggered by promoter-targeted small double stranded RNAs (dsRNAs), also known as small activating RNAs (saRNAs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26401871", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Ivosidenib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29266015", "http://www.ncbi.nlm.nih.gov/pubmed/29950729", "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "http://www.ncbi.nlm.nih.gov/pubmed/30466743", "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "http://www.ncbi.nlm.nih.gov/pubmed/30209701", "http://www.ncbi.nlm.nih.gov/pubmed/30093505", "http://www.ncbi.nlm.nih.gov/pubmed/29934313" ], "ideal_answer": [ "Ivosidenib is an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models. It is effective for IDH1-mutant relapsed/refractory acute myeloid leukemia." ], "type": "summary", "id": "5c58a0e486df2b917400000c", "snippets": [ { "offsetInBeginSection": 963, "offsetInEndSection": 1188, "text": " Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29266015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "endSection": "title" }, { "offsetInBeginSection": 460, "offsetInEndSection": 687, "text": "Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "A phase I study suggests that ivosidenib can induce remission in patients with relapsed or refractory acute myeloid leukemia characterized by IDH1 mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934313", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 344, "text": " Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.METHODS: We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 1997, "offsetInEndSection": 2326, "text": "CONCLUSIONS: In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1564, "text": "Biochemical studies predicted that resistance to allosteric IDH inhibitors could also occur via IDH dimer-interface mutations in cis, which was confirmed in a patient with acquired resistance to the IDH1 inhibitor ivosidenib (AG-120). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29950729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30093505", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 362, "text": "Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.
METHODS: We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" } ] }, { "body": "Which is the basis of the ATAC-Seq protocol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25559105", "http://www.ncbi.nlm.nih.gov/pubmed/29052193", "http://www.ncbi.nlm.nih.gov/pubmed/29605854", "http://www.ncbi.nlm.nih.gov/pubmed/30375457", "http://www.ncbi.nlm.nih.gov/pubmed/30421411", "http://www.ncbi.nlm.nih.gov/pubmed/29155775", "http://www.ncbi.nlm.nih.gov/pubmed/28550296", "http://www.ncbi.nlm.nih.gov/pubmed/28846090", "http://www.ncbi.nlm.nih.gov/pubmed/25679813" ], "ideal_answer": [ "This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription-factor binding and nucleosome position. The method is a fast and sensitive alternative to DNase-seq for assaying chromatin accessibility genome-wide, or to MNase-seq for assaying nucleosome positions in accessible regions of the genome.", "ATAC-Seq probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription-factor binding and nucleosome position.", "This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription-factor binding and nucleosome position." ], "type": "summary", "id": "5c34b45eda8336e21a000008", "snippets": [ { "offsetInBeginSection": 165, "offsetInEndSection": 469, "text": "This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription-factor binding and nucleosome position.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25559105", "endSection": "abstract" }, { "offsetInBeginSection": 470, "offsetInEndSection": 666, "text": "The method is a fast and sensitive alternative to DNase-seq for assaying chromatin accessibility genome-wide, or to MNase-seq for assaying nucleosome positions in accessible regions of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25559105", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1416, "text": "This comprehensive protocol begins with cell harvest, then describes the molecular procedure of chromatin tagmentation, sample preparation for next-generation sequencing, and also includes methods and considerations for the computational analyses used to interpret the results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) is a method used for the identification of open (accessible) regions of chromatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155775", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 839, "text": "ATAC-seq, based on preferential integration of a transposon into open chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25679813", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 504, "text": "Assay for Transposase Accessible Chromatin (ATAC-seq) technology can interrogate chromatin accessibility from small cell numbers and facilitate studying enhancers in pathologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30375457", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 313, "text": "Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) is a powerful technique for identifying nucleosome-free regions of the genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30421411", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 877, "text": "Recently a new technique coupled with high-throughput sequencing named Assay for Transposase Accessible Chromatin (ATAC-seq) emerged as an efficient method to chart open chromatin genome wide. The application of such technique to different cell types allowed unmasking tissue-specific regulatory elements and characterizing cis-regulatory networks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29605854", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 606, "text": "This technique utilizes a hyperactive Tn5 transposase to cause DNA cleavage and simultaneous insertion of sequencing adapters into open chromatin regions of the input nuclei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29052193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) is a method used for the identification of open (accessible) regions of chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155775", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 1000, "text": "ATAC-seq is a robust and sensitive alternative to DNase I hypersensitivity analysis coupled with next-generation sequencing (DNase-seq) and formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) for genome-wide analysis of chromatin accessibility and to the sequencing of micrococcal nuclease-sensitive sites (MNase-seq) to determine nucleosome positioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "ATAC-seq is a high-throughput sequencing technique that identifies open chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28550296", "endSection": "abstract" } ] }, { "body": "What is vcfanno?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27250555" ], "ideal_answer": [ "Vcfanno flexibly extracts and summarizes attributes from multiple annotation files and integrates the annotations within the INFO column of the original VCF file. Substantial performance gains are reported by annotating ~85,000 variants per second with 50 attributes from 17 commonly used genome annotation resources. Vcfanno is available at https://github.com/brentp/vcfanno under the MIT license." ], "type": "summary", "id": "5c597a5086df2b9174000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Vcfanno: fast, flexible annotation of genetic variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27250555", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 735, "text": "The integration of genome annotations is critical to the identification of genetic variants that are relevant to studies of disease or other traits. However, comprehensive variant annotation with diverse file formats is difficult with existing methods. Here we describe vcfanno, which flexibly extracts and summarizes attributes from multiple annotation files and integrates the annotations within the INFO column of the original VCF file. By leveraging a parallel \"chromosome sweeping\" algorithm, we demonstrate substantial performance gains by annotating ~85,000 variants per second with 50 attributes from 17 commonly used genome annotation resources. Vcfanno is available at https://github.com/brentp/vcfanno under the MIT license.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27250555", "endSection": "abstract" } ] }, { "body": "What is the association of Disease-Associated STRs (daSTRs) with domain boundaries?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30173918" ], "ideal_answer": [ "Nearly all disease-associated STRs (daSTRs) are located at boundaries demarcating 3D chromatin domains. For instance, Fragile X syndrome patients exhibit severe boundary disruption in a manner that correlates with local loss of CTCF occupancy and the degree of FMR1 silencing." ], "type": "summary", "id": "5c53242b7e3cb0e231000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30173918", "endSection": "title" }, { "offsetInBeginSection": 314, "offsetInEndSection": 1015, "text": "Here, we discover that nearly all disease-associated STRs (daSTRs) are located at boundaries demarcating 3D chromatin domains. We identify a subset of boundaries with markedly higher CpG island density compared to the rest of the genome. daSTRs specifically localize to ultra-high-density CpG island boundaries, suggesting they might be hotspots for epigenetic misregulation or topological disruption linked to STR expansion. Fragile X syndrome patients exhibit severe boundary disruption in a manner that correlates with local loss of CTCF occupancy and the degree of FMR1 silencing. Our data uncover higher-order chromatin architecture as a new dimension in understanding repeat expansion disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30173918", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 440, "text": "Here, we discover that nearly all disease-associated STRs (daSTRs) are located at boundaries demarcating 3D chromatin domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30173918", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 739, "text": "daSTRs specifically localize to ultra-high-density CpG island boundaries, suggesting they might be hotspots for epigenetic misregulation or topological disruption linked to STR expansion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30173918", "endSection": "abstract" } ] }, { "body": "What is the link between ultraconserved elements and three-dimensional mammalian genome organization?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29996107" ], "ideal_answer": [ "Ultraconserved elements (UCEs) occupy specific arenas of three-dimensional mammalian genome organization. UCEs are enriched within contact domains and, further, that the subset of UCEs within domains shared across diverse cell types are linked to kidney-related and neuronal processes. In boundaries, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither overrepresented nor underrepresented, but those present in loop anchors are enriched for splice sites. As the relationships between UCEs and human Hi-C features are conserved in mouse, UCEs contribute to interspecies conservation of genome organization and, thus, genome stability." ], "type": "summary", "id": "5c52ca7c7e3cb0e23100000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Ultraconserved Elements Occupy Specific Arenas of Three-Dimensional Mammalian Genome Organization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29996107", "endSection": "title" }, { "offsetInBeginSection": 393, "offsetInEndSection": 1063, "text": "We find that UCEs are enriched within contact domains and, further, that the subset of UCEs within domains shared across diverse cell types are linked to kidney-related and neuronal processes. In boundaries, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither overrepresented nor underrepresented, but those present in loop anchors are enriched for splice sites. Finally, as the relationships between UCEs and human Hi-C features are conserved in mouse, our findings suggest that UCEs contribute to interspecies conservation of genome organization and, thus, genome stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29996107", "endSection": "abstract" } ] }, { "body": "What are the \"Ohnologs\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27297469", "http://www.ncbi.nlm.nih.gov/pubmed/28658311", "http://www.ncbi.nlm.nih.gov/pubmed/23917329", "http://www.ncbi.nlm.nih.gov/pubmed/28482005", "http://www.ncbi.nlm.nih.gov/pubmed/17068775", "http://www.ncbi.nlm.nih.gov/pubmed/26181593" ], "ideal_answer": [ "Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation.", "Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs -paralogous gene pairs generated by whole genome duplication- are enriched for dosage sensitive genes, that is, genes that have a phenotype due to copy number changes", "Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation." ], "type": "summary", "id": "5c3479dcda8336e21a000002", "snippets": [ { "offsetInBeginSection": 220, "offsetInEndSection": 382, "text": "Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26181593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Ohnologs -paralogous gene pairs generated by whole genome duplication- are enriched for dosage sensitive genes, that is, genes that have a phenotype due to copy number changes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27297469", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 683, "text": "Ohnologs are paralogs stemming from such genome duplication events, and some zebrafish genes said to be \"novel\" are more appropriately interpreted as \"ohnologs gone missing\", cases in which ohnologs are preserved differentially in different evolutionary lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17068775", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 336, "text": "Copy number variations are distributed non-randomly in vertebrate genomes, and it was recently reported that ohnologs, which are duplicated genes derived from whole genome duplication, are refractory to copy number variations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23917329", "endSection": "abstract" } ] }, { "body": "What is TissueEnrich?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30346488" ], "ideal_answer": [ "TissueEnrich is a tool that calculates tissue-specific gene enrichment in an input gene set. TissueEnrich can assign tissue identities to single cell clusters and differentiated embryonic stem cells." ], "type": "summary", "id": "5c58d9db86df2b9174000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "TissueEnrich: Tissue-specific gene enrichment analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346488", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 985, "text": "While tools have been developed to identify biological processes that are enriched in the genes sets, there remains a need for tools that identify enrichment of tissue-specific genes. Therefore, we developed TissueEnrich, a tool that calculates tissue-specific gene enrichment in an input gene set. We demonstrated that TissueEnrich can assign tissue identities to single cell clusters and differentiated embryonic stem cells.Availability: The TissueEnrich web application is freely available at http://tissueenrich.gdcb.iastate.edu/. The R package is available through Bioconductor at https://bioconductor.org/packages/TissueEnrich. Both the web application and R package are for non-profit academic use under the MIT license.Supplementary information: Supplementary data are available at Bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346488", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 478, "text": "Therefore, we developed TissueEnrich, a tool that calculates tissue-specific gene enrichment in an input gene set.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346488", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 725, "text": "We demonstrated that TissueEnrich can assign tissue identities to single cell clusters and differentiated embryonic stem cells.
Availability: The TissueEnrich web application is freely available at http://tissueenrich.gdcb.iastate.edu/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346488", "endSection": "abstract" } ] }, { "body": "Describe OligoSTORM", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28924672" ], "ideal_answer": [ "OligoSTORM and OligoDNA-PAINT meld the Oligopaint technology for fluorescent in situ hybridization (FISH) with, respectively, Stochastic Optical Reconstruction Microscopy (STORM) and DNA-based Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) to enable in situ single-molecule super-resolution imaging of nucleic acids. Both strategies enable \u226420 nm resolution and are appropriate for imaging nanoscale features of the genomes of a wide range of species, including human, mouse, and fruit fly (Drosophila)." ], "type": "summary", "id": "5c54496907647bbc4b000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "In Situ Super-Resolution Imaging of Genomic DNA with OligoSTORM and OligoDNA-PAINT.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28924672", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 523, "text": "OligoSTORM and OligoDNA-PAINT meld the Oligopaint technology for fluorescent in situ hybridization (FISH) with, respectively, Stochastic Optical Reconstruction Microscopy (STORM) and DNA-based Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) to enable in situ single-molecule super-resolution imaging of nucleic acids. Both strategies enable \u226420\u00a0nm resolution and are appropriate for imaging nanoscale features of the genomes of a wide range of species, including human, mouse, and fruit fly (Drosophila).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28924672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "OligoSTORM and OligoDNA-PAINT meld the Oligopaint technology for fluorescent in situ hybridization (FISH) with, respectively, Stochastic Optical Reconstruction Microscopy (STORM) and DNA-based Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) to enable in situ single-molecule super-resolution imaging of nucleic acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28924672", "endSection": "abstract" } ] }, { "body": "Which metabolic pathways have been associated with Systemic Lupus Erythematosus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24333266", "http://www.ncbi.nlm.nih.gov/pubmed/24772967", "http://www.ncbi.nlm.nih.gov/pubmed/20477100", "http://www.ncbi.nlm.nih.gov/pubmed/8159911", "http://www.ncbi.nlm.nih.gov/pubmed/25648260", "http://www.ncbi.nlm.nih.gov/pubmed/20305046", "http://www.ncbi.nlm.nih.gov/pubmed/24494566", "http://www.ncbi.nlm.nih.gov/pubmed/24040398" ], "ideal_answer": [ "Genetic polymorphisms of the xenobiotic metabolic pathway involved in estrogen metabolism might contribute towards pathophysiology of systemic lupus erythematosus (SLE). According to the analysis on metabolic pathway, SLE could cause significant changes in unsaturated fatty acid and amino acid metabolism pathway. Results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism" ], "exact_answer": [ [ "Estrogen metabolism" ], [ "Unsaturated fatty acid metabolism" ], [ "Amino acid metabolism" ], [ "Glycosphingolipid metabolism" ], [ "One-carbon metabolic pathway" ] ], "type": "list", "id": "5c34a761da8336e21a000005", "snippets": [ { "offsetInBeginSection": 202, "offsetInEndSection": 348, "text": "Measurement of urine neopterin, product of a metabolic pathway controlled by interferon-gamma, has been found useful in many clinical conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8159911", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 459, "text": "The objective of this study was to investigate the association between genetic variations in estrogen metabolic pathway genes, including estrogen receptor alpha (ESR1), estrogen receptor beta (ESR2), and aromatase (CYP19A1), and risk of SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20305046", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1092, "text": "According to the analysis on metabolic pathway, SLE could cause significant changes in unsaturated fatty acid and amino acid metabolism pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24494566", "endSection": "abstract" }, { "offsetInBeginSection": 1372, "offsetInEndSection": 1584, "text": "Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040398", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 292, "text": "genetic polymorphisms of the xenobiotic metabolic pathway involved in estrogen metabolism might contribute towards pathophysiology of systemic lupus erythematosus (SLE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24772967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "The current study was conducted to elucidate the effect of genetic variations in one-carbon metabolism on the epigenetic regulation of major histocompatibility complex II transactivator (MHC2TA), reduced folate carrier 1 (RFC1/SLC19A1) and human leukocyte antigen (HLA)-DR in systemic lupus erythematosus (SLE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24333266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Putatively functional polymorphisms of one-carbon and xenobiotic metabolic pathways influence susceptibility for wide spectrum of diseases. The current study was aimed to explore gene-gene interactions among these two metabolic pathways in four diseases i.e. breast cancer, systemic lupus erythematosus (SLE), coronary artery disease (CAD) and Parkinson's disease (PD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25648260", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 788, "text": "In this regard, inflammation is not only associated with systemic lupus patients but is also present in patients with metabolic syndrome and insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20477100", "endSection": "abstract" } ] }, { "body": "What are the 3 main bacteria found in human milk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27940404" ], "ideal_answer": [ "Human milk is rich in diverse bacteria, particularly Staphylococcus, Streptococcus and Pseudomonas genera." ], "exact_answer": [ [ "Staphylococcus" ], [ "Streptococcus" ], [ "Pseudomonas" ] ], "type": "list", "id": "5be44d8b133db5eb78000015", "snippets": [ { "offsetInBeginSection": 56, "offsetInEndSection": 213, "text": "Instead, it provides infants a rich source of diverse bacteria, particularly microbes belonging to the Staphylococcus, Streptococcus, and Pseudomonas genera.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940404", "endSection": "abstract" } ] }, { "body": "Which algorithm has been developed for trio-based benchmarking of variant calls?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29850774" ], "ideal_answer": [ "Geck is a tool for trio-based comparative benchmarking tool of variant calls. It is a statistical mixture model for comparing two variant calling pipelines from genotype data they produce after running on individual members of a trio." ], "exact_answer": [ "geck" ], "type": "factoid", "id": "5c581e1507647bbc4b00001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "geck: trio-based comparative benchmarking of variant calls.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850774", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 997, "text": "Classical methods of comparing the accuracies of variant calling pipelines are based on truth sets of variants whose genotypes are previously determined with high confidence. An alternative way of performing benchmarking is based on Mendelian constraints between related individuals. Statistical analysis of Mendelian violations can provide truth set-independent benchmarking information, and enable benchmarking less-studied variants and diverse populations.Results: We introduce a statistical mixture model for comparing two variant calling pipelines from genotype data they produce after running on individual members of a trio. We determine the accuracy of our model by comparing the precision and recall of GATK Unified Genotyper and Haplotype Caller on the high-confidence SNPs of the NIST Ashkenazim trio and the two independent Platinum Genome trios. We show that our method is able to estimate differential precision and recall between the two pipelines with 10-3 uncertainty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850774", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by Caplacizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23307200", "http://www.ncbi.nlm.nih.gov/pubmed/29209322", "http://www.ncbi.nlm.nih.gov/pubmed/29807376", "http://www.ncbi.nlm.nih.gov/pubmed/28139813", "http://www.ncbi.nlm.nih.gov/pubmed/28445600", "http://www.ncbi.nlm.nih.gov/pubmed/30298461", "http://www.ncbi.nlm.nih.gov/pubmed/28645643", "http://www.ncbi.nlm.nih.gov/pubmed/28110841", "http://www.ncbi.nlm.nih.gov/pubmed/30046703", "http://www.ncbi.nlm.nih.gov/pubmed/26863353" ], "ideal_answer": [ "Caplacizumab is anti-von Willebrand factor (VWF) antibody that blocks the interaction between VWF and platelets. It is used for treatment of acquired thrombotic thrombocytopenic purpura (aTTP)." ], "exact_answer": [ "von Willebrand factor" ], "type": "factoid", "id": "5c55d9b707647bbc4b000009", "snippets": [ { "offsetInBeginSection": 527, "offsetInEndSection": 766, "text": "Caplacizumab, a nanobody that blocks the interaction between VWF and platelets, has shown promising results in decreasing the time to recover from the acute events that will hopefully translate into long-term clinical benefit for patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30046703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Ablynx, a Sanofi Company, has developed the anti-von Willebrand factor Nanobody\u00ae caplacizumab (Cablivi\u2122) for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30298461", "endSection": "abstract" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1381, "text": "Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13 and caplacizumab, an inhibitor of the glycoprotein-Ib/IX-von Willebrand factor axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28110841", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 625, "text": "The most promising candidates for future treatment of TTP are: rituximab for termination of the autoimmune process, caplacizumab for prevention of platelet-VWF-interaction, and recombinant ADAMTS13 for replacement of the inhibited or missing enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139813", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1470, "text": "Promising agents under evaluation include caplacizumab (an inhibitor of the glycoprotein-Ib/IX-Von-Willebrand factor axis), N-acetylcysteine, recombinant ADAMTS13, and anti-plasmocyte compounds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28645643", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 885, "text": " In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody\u00ae was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28445600", "endSection": "abstract" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1326, "text": "It is now anticipated that the first VHH-based antibody drug, Caplacizumab, a bivalent anti-vWF antibody for treating rare blood clotting disorders, may be approved and commercialized in 2018 or shortly thereafter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29209322", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 610, "text": "Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high.
METHODS: Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26863353", "endSection": "abstract" } ] }, { "body": "In which tissues is the lincRNA Xist expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25548914", "http://www.ncbi.nlm.nih.gov/pubmed/21241365", "http://www.ncbi.nlm.nih.gov/pubmed/10026129", "http://www.ncbi.nlm.nih.gov/pubmed/23122604", "http://www.ncbi.nlm.nih.gov/pubmed/17373633", "http://www.ncbi.nlm.nih.gov/pubmed/1345168", "http://www.ncbi.nlm.nih.gov/pubmed/22925639" ], "ideal_answer": [ "Relative expression of X-linked genes was examined in liver, kidney and brain tissue by real-time PCR in adult XX(Y)* and XY* males and XX females. X-chromosome inactive specific transcript (Xist) was expressed only in female adipose tissue. X-chromosome inactive specific transcript (Xist) was expressed only in female adipose tissue. It was also expressed in duodenum and testis." ], "exact_answer": [ [ "duodenum" ], [ "kidney" ], [ "brain" ], [ "liver" ], [ "adipose tissue" ], [ "testis" ] ], "type": "list", "id": "5be2a070133db5eb78000013", "snippets": [ { "offsetInBeginSection": 838, "offsetInEndSection": 1044, "text": "Xist (female-only) and Eif2s3y (male-only). The frequency of SDE probesets varied widely between tissues, and was highest in the duodenum (6.2%), whilst less than 0.05% in over half of the surveyed tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25548914", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1407, "text": "Embryos positive for Xist expression were classified as female, and Xist negative and equine sex determining region of the Y chromosome positive embryos were classified as male. From 28 embryos tested, 15 (54%) showed positive Xist expression and were thus classified as female.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23122604", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 620, "text": "Preattachment embryos at different times after ovulation (Day 8: n = 9; Day 10: n = 12; Day 12: n = 15) were analyzed for Xist RNA expression using quantitative and qualitative reverse transcription-polymerase chain reaction (RT-PCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22925639", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 669, "text": "Relative expression of X-linked genes was examined in liver, kidney and brain tissue by real-time PCR in adult XX(Y)* and XY* males and XX females", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21241365", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 958, "text": "X-chromosome inactive specific transcript (Xist) was expressed only in female adipose tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17373633", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 571, "text": "Reverse transcription-polymerase chain reaction (RT-PCR) revealed the presence of Xist transcripts in all adult female somatic tissues evaluated. In contrast, among the male tissues examined, Xist expression was detected only in testis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10026129", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 533, "text": "We now report the presence of Xist/XIST transcripts in newborn and adult mouse testes, and in human testicular tissue with normal spermatogenesis, but not in the testes of patients who lack germ cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1345168", "endSection": "abstract" } ] }, { "body": "Which is the main component of the Lewy body?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28784297", "http://www.ncbi.nlm.nih.gov/pubmed/27986376", "http://www.ncbi.nlm.nih.gov/pubmed/28780180", "http://www.ncbi.nlm.nih.gov/pubmed/26667592" ], "ideal_answer": [ "Lewy bodies comprise of aggregated intracellular vesicles and proteins and \u03b1-synuclein is reported to be a major protein component." ], "exact_answer": [ "Lewy bodies comprise of aggregated intracellular vesicles and proteins and \u03b1-synuclein is reported to be a major protein component." ], "type": "factoid", "id": "5ad4d758133db5eb78000007", "snippets": [ { "offsetInBeginSection": 209, "offsetInEndSection": 319, "text": "neuronal inclusions composed of \u03b1-synuclein (Lewy bodies) is considered the typical pathologic correlate of PD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28780180", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 695, "text": " the era of alpha-synuclein, the protein present in Lewy bodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28784297", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 331, "text": "Lewy bodies comprise of aggregated intracellular vesicles and proteins and \u03b1-synuclein is reported to be a major protein component. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26667592", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 401, "text": "he Lewy body constituents, \u03b1-synuclein and small ubiquitin-related modifier-1(SUMO-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986376", "endSection": "abstract" } ] }, { "body": "What forms part of the senescence associated secretory phenotype, or SASP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28741506", "http://www.ncbi.nlm.nih.gov/pubmed/23296657", "http://www.ncbi.nlm.nih.gov/pubmed/26943583", "http://www.ncbi.nlm.nih.gov/pubmed/27812871", "http://www.ncbi.nlm.nih.gov/pubmed/22020330", "http://www.ncbi.nlm.nih.gov/pubmed/28217839", "http://www.ncbi.nlm.nih.gov/pubmed/27731420" ], "ideal_answer": [ "The diverse arrays of proteins secreted by senescent cells have been described to influence aging and to have both pro-tumorigenic and anti-tumorigenic influences on the surrounding microenvironment. Further characterization of these proteins, known as the senescence-associated secretory phenotype (SASP), and their regulators is required to understand and further manipulate such activities. The senescence-associated secretory phenotype (SASP) is characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and other pro-inflammatory factors including a novel SASP component CLEC11A.", "Numerous activities of senescent cells depend on the aptitude of these cells to secrete myriads of bioactive molecules, a behavior termed the senescence-associated secretory phenotype (SASP) The SASP supports cell-autonomous functions like the senescence-associated growth arrest, and mediates paracrine interactions between senescent cells and their surrounding microenvironment. Cultures enriched with not-diploid cells acquired a senescence-associated secretory phenotype (SASP) characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and other pro-inflammatory factors including a novel SASP component CLEC11A." ], "exact_answer": [ [ "IL1B" ], [ "CXCL8" ], [ "CCL2" ], [ "TNF" ], [ "CCL27" ] ], "type": "list", "id": "5c0e82b2133db5eb7800002d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "SASP mediates chemoresistance and tumor-initiating-activity of mesothelioma cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020330", "endSection": "title" }, { "offsetInBeginSection": 175, "offsetInEndSection": 365, "text": "Numerous activities of senescent cells depend on the aptitude of these cells to secrete myriads of bioactive molecules, a behavior termed the senescence-associated secretory phenotype (SASP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23296657", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 556, "text": "The SASP supports cell-autonomous functions like the senescence-associated growth arrest, and mediates paracrine interactions between senescent cells and their surrounding microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23296657", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 1024, "text": "Cultures enriched with not-diploid cells acquired a senescence-associated secretory phenotype (SASP) characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and other pro-inflammatory factors including a novel SASP component CLEC11A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27731420", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 448, "text": "Senescent cells secrete cytokines and other factors of the senescence-associated secretory phenotype (SASP) that contribute to tumor suppression by enforcing arrest and recruiting immune cells that remove these damaged or oncogene-expressing cells from organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28741506", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 503, "text": "Aim of this study was to evaluate whether and how adalimumab, a monoclonal antibody directed against tumor necrosis factor-\u03b1 (TNF-\u03b1), a major SASP component, can prevent the SASP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26943583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Endothelial cell senescence is characterized by acquisition of senescence-associated secretory phenotype (SASP), able to promote inflammaging and cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26943583", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 422, "text": "We have shown that the mitochondria are essential for development of senescence and many of the associated phenotypes, including the often detrimental senescence-associated secretory phenotype (SASP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28217839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "The diverse arrays of proteins secreted by senescent cells have been described to influence aging and to have both pro-tumorigenic and anti-tumorigenic influences on the surrounding microenvironment. Further characterization of these proteins, known as the senescence-associated secretory phenotype (SASP), and their regulators is required to understand and further manipulate such activities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812871", "endSection": "abstract" } ] }, { "body": "How many pseudogenes are contained in the C. elegans genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11997343", "http://www.ncbi.nlm.nih.gov/pubmed/24463456", "http://www.ncbi.nlm.nih.gov/pubmed/15916954" ], "ideal_answer": [ "Evidence suggests that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes. At least 4% of the annotated C. elegans genes can be recognized as pseudogenes simply from closer inspection of the sequence data. Thus out of 18000 transcripts, around 3500 are expected to be pseudogenes.", "Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes The remaining explanation is that most of the annotated genes in the recently duplicated category are pseudogenes, a proportion corresponding to 20% of all of the annotated C. elegans genes At least 4% of the annotated C. elegans genes can be recognized as pseudogenes simply from closer inspection of the sequence data", "Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes" ], "exact_answer": [ "3600" ], "type": "factoid", "id": "5c2cf051133db5eb78000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11997343", "endSection": "title" }, { "offsetInBeginSection": 445, "offsetInEndSection": 634, "text": "The remaining explanation is that most of the annotated genes in the recently duplicated category are pseudogenes, a proportion corresponding to 20% of all of the annotated C. elegans genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11997343", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1079, "text": " At least 4% of the annotated C. elegans genes can be recognized as pseudogenes simply from closer inspection of the sequence data", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11997343", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 646, "text": "over 18,000 transcripts in each sample", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24463456", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 635, "text": "The remaining explanation is that most of the annotated genes in the recently duplicated category are pseudogenes, a proportion corresponding to 20% of all of the annotated C. elegans genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11997343", "endSection": "abstract" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1080, "text": "At least 4% of the annotated C. elegans genes can be recognized as pseudogenes simply from closer inspection of the sequence data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11997343", "endSection": "abstract" } ] }, { "body": "What is a Aquaporin channel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26870725" ], "ideal_answer": [ "Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostics and therapeutics." ], "exact_answer": [ "Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes." ], "type": "factoid", "id": "5c5f08ad1a4c55d80b00000b", "snippets": [ { "offsetInBeginSection": 202, "offsetInEndSection": 564, "text": "Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostics and therapeutics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26870725", "endSection": "abstract" } ] }, { "body": "What is cluster of differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29208350", "http://www.ncbi.nlm.nih.gov/pubmed/29243545", "http://www.ncbi.nlm.nih.gov/pubmed/11381193" ], "ideal_answer": [ "Cluster of Differentiation (CD) are cellular antigens used to identify cell populations, such as T-lymphocyte populations and macrophages." ], "exact_answer": [ "Cluster of Differentiation (CD) are cellular antigens used to identify cell populations, such as T-lymphocyte populations and macrophages." ], "type": "factoid", "id": "5c5f0d071a4c55d80b000010", "snippets": [ { "offsetInBeginSection": 510, "offsetInEndSection": 615, "text": "The characterisation of the MSCs was determined by their cluster of differentiation (CD) marker profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29208350", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 531, "text": "The samples were immunohistochemically stained for cluster of differentiation (CD)4, CD8, CD16, CD25, CD56 and CD68 using immunofluorescence in order to identify different T-lymphocyte populations and macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29243545", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 304, "text": " definition of recognised cellular antigens (designated by CD: Cluster of Differentiation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11381193", "endSection": "abstract" } ] }, { "body": "List two medication included in the Juluca pill.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30406902" ], "ideal_answer": [ "Juluca\u00ae pill includes dolutegravir and rilpivirine. It is the first two-drug single-tablet regimen (STR) to be approved for the treatment of HIV-1 infection in adults." ], "exact_answer": [ [ "dolutegravir" ], [ "rilpivirine" ] ], "type": "list", "id": "5c61cdd7e842deac67000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Dolutegravir/rilpivirine (Juluca\u00ae) is the first two-drug single-tablet regimen (STR) to be approved for the treatment of HIV-1 infection in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30406902", "endSection": "abstract" } ] }, { "body": "Which tool has been developed for tagging biomedical concepts via interactive learning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29788413" ], "ideal_answer": [ "ezTag is a web-based annotation tool that supports annotating a wide variety of biological concepts with or without pre-existing training data. It allows curators to perform annotation and provide training data with humans in the loop. ezTag supports both abstracts in PubMed and full-text articles in PubMed Central. It also provides lexicon-based concept tagging as well as the state-of-the-art pre-trained taggers such as TaggerOne, GNormPlus and tmVar. ezTag is freely available at http://eztag.bioqrator.org." ], "exact_answer": [ "ezTag" ], "type": "factoid", "id": "5c56b96e07647bbc4b000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "ezTag: tagging biomedical concepts via interactive learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29788413", "endSection": "title" }, { "offsetInBeginSection": 351, "offsetInEndSection": 874, "text": "To support annotating a wide variety of biological concepts with or without pre-existing training data, we developed ezTag, a web-based annotation tool that allows curators to perform annotation and provide training data with humans in the loop. ezTag supports both abstracts in PubMed and full-text articles in PubMed Central. It also provides lexicon-based concept tagging as well as the state-of-the-art pre-trained taggers such as TaggerOne, GNormPlus and tmVar. ezTag is freely available at http://eztag.bioqrator.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29788413", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 596, "text": "To support annotating a wide variety of biological concepts with or without pre-existing training data, we developed ezTag, a web-based annotation tool that allows curators to perform annotation and provide training data with humans in the loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29788413", "endSection": "abstract" } ] }, { "body": "Which cells produce Interleukin 17A?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28930285", "http://www.ncbi.nlm.nih.gov/pubmed/28941323", "http://www.ncbi.nlm.nih.gov/pubmed/28935156" ], "ideal_answer": [ "Interleukin (IL)-17A is secreted from T helper type 17 (TH17) cells." ], "exact_answer": [ "T helper type 17 (TH17) cells." ], "type": "factoid", "id": "5c5f30c91a4c55d80b000025", "snippets": [ { "offsetInBeginSection": 207, "offsetInEndSection": 306, "text": "Several studies have shown an increased expression/release of Th17 related cytokine, IL-17A in ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28935156", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 323, "text": " interleukin (IL)-17A, secreted from T helper type 17 (TH17) cells,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28930285", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 806, "text": " IL-17A, markedly produced by TH17 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28930285", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 764, "text": "IL-22 and IL-17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL-22+ Th17 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941323", "endSection": "abstract" } ] }, { "body": "Is durvalumab used for lung cancer treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29069302", "http://www.ncbi.nlm.nih.gov/pubmed/29303787", "http://www.ncbi.nlm.nih.gov/pubmed/29593890", "http://www.ncbi.nlm.nih.gov/pubmed/29140105", "http://www.ncbi.nlm.nih.gov/pubmed/28664936", "http://www.ncbi.nlm.nih.gov/pubmed/30489337", "http://www.ncbi.nlm.nih.gov/pubmed/28705024", "http://www.ncbi.nlm.nih.gov/pubmed/29239189", "http://www.ncbi.nlm.nih.gov/pubmed/30116683", "http://www.ncbi.nlm.nih.gov/pubmed/29958099", "http://www.ncbi.nlm.nih.gov/pubmed/28585617", "http://www.ncbi.nlm.nih.gov/pubmed/29358503", "http://www.ncbi.nlm.nih.gov/pubmed/29760563", "http://www.ncbi.nlm.nih.gov/pubmed/30012210", "http://www.ncbi.nlm.nih.gov/pubmed/29545095", "http://www.ncbi.nlm.nih.gov/pubmed/28885881", "http://www.ncbi.nlm.nih.gov/pubmed/27196116", "http://www.ncbi.nlm.nih.gov/pubmed/28960263", "http://www.ncbi.nlm.nih.gov/pubmed/28512504", "http://www.ncbi.nlm.nih.gov/pubmed/30327351" ], "ideal_answer": [ "Yes, Durvalumab is an anti-PDL-1 antibody that is used for treatment of non-small-cell lung cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5c5607aa07647bbc4b00000e", "snippets": [ { "offsetInBeginSection": 1047, "offsetInEndSection": 1253, "text": " In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30489337", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 628, "text": "METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Durvalumab in non-small-cell lung cancer patients: current developments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29140105", "endSection": "title" }, { "offsetInBeginSection": 302, "offsetInEndSection": 463, "text": "Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the \u226525% PD-L1+ population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29140105", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 964, "text": "Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29303787", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 1073, "text": "In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358503", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 330, "text": "ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28705024", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1337, "text": "The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28705024", "endSection": "abstract" } ] }, { "body": "Is LRP1 interacting with Urokinase receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19008962", "http://www.ncbi.nlm.nih.gov/pubmed/11359936" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "type": "yesno", "id": "5c5f0c5a1a4c55d80b00000f", "snippets": [ { "offsetInBeginSection": 367, "offsetInEndSection": 581, "text": " Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19008962", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 328, "text": "Here we investigated whether direct interaction between uPAR, a glycosyl-phosphatidylinositol-anchored protein, and LRP, a transmembrane receptor,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11359936", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1062, "text": "Direct binding of domain 3 (D3) of uPAR to LRP is required for clearance of uPA-PAI-1-occupied uPAR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11359936", "endSection": "abstract" } ] }, { "body": "Is obesity related to cognitive decline?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28837952", "http://www.ncbi.nlm.nih.gov/pubmed/26928024", "http://www.ncbi.nlm.nih.gov/pubmed/26638123", "http://www.ncbi.nlm.nih.gov/pubmed/28514983", "http://www.ncbi.nlm.nih.gov/pubmed/22258511", "http://www.ncbi.nlm.nih.gov/pubmed/26107577", "http://www.ncbi.nlm.nih.gov/pubmed/15591798", "http://www.ncbi.nlm.nih.gov/pubmed/23922324", "http://www.ncbi.nlm.nih.gov/pubmed/26163814", "http://www.ncbi.nlm.nih.gov/pubmed/25496905", "http://www.ncbi.nlm.nih.gov/pubmed/24119725", "http://www.ncbi.nlm.nih.gov/pubmed/28284174" ], "ideal_answer": [ "Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions. Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance." ], "exact_answer": "yes", "type": "yesno", "id": "5c0e838b133db5eb7800002e", "snippets": [ { "offsetInBeginSection": 623, "offsetInEndSection": 800, "text": "The initial results suggests that obese children have higher cognitive scores and that this result is driven by those who are female, non-indigenous and live in an urban region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28284174", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1367, "text": "On the other end of the weight distribution, indigenous children who are severely thin or thin have significantly lower cognitive scores, a relationship that holds after correcting for possible bias and appears to strengthen between ages of five and eight.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28284174", "endSection": "abstract" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1651, "text": "Obesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28837952", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 876, "text": "The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26107577", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 645, "text": "Poor cognitive performance was present in 37% of the sample. General obesity (BMI>or = 25) and poor cognition were strongly associated in the presence of abdominal obesity. Poor cognition was negatively associated with overweight (BMI 23-25) with normal waist circumference.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15591798", "endSection": "abstract" }, { "offsetInBeginSection": 1450, "offsetInEndSection": 1622, "text": "BMI could be used as a candidate risk marker to identify people at higher risk of cognitive deficits, and as an intervention target for modifications of cognitive outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119725", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 187, "text": "Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26928024", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1398, "text": "Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23922324", "endSection": "abstract" }, { "offsetInBeginSection": 1316, "offsetInEndSection": 1411, "text": "Impairments in cognitive function have been associated with obesity in both people and rodents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25496905", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1203, "text": "Obesity in the pre-school years was associated with poorer outcomes for some cognitive measures in this study. Stronger relationships between obesity and cognition or educational attainment may emerge later in childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26638123", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 287, "text": "There is parallel evidence that people who are overweight or obese tend to perform worse on a variety of cognitive tasks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28514983", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 402, "text": "While research in this area is growing, our knowledge of obesity-related cognitive dysfunction and brain alterations has not yet been synthesized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258511", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 613, "text": "The present review integrates the recent literature regarding patterns of obesity-related cognitive dysfunction and brain alterations and also indicates potential mechanisms for these neuropathological changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258511", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 813, "text": "The review culminates in a preliminary model of obesity-related cognitive dysfunction and suggestions for future research, including the potential reversibility of these changes with weight-loss.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258511", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 637, "text": "Evidence for the increased prevalence of diabetes and obesity is reviewed as it relates to cognitive decline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163814", "endSection": "abstract" }, { "offsetInBeginSection": 638, "offsetInEndSection": 877, "text": "These articles indicate that the age of onset of Type 1 diabetes may be relevant to future cognitive function and that disease duration of Type 2 diabetes and sociocultural factors are related to cognitive decline during the aging process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163814", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1403, "text": "This special issue concludes with a conceptual framework for linking obesity and diabetes with accelerated cognitive decline as related to the aging process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163814", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 271, "text": "The adverse effects of diabetes and obesity on cognitive functioning are increasingly well recognized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163814", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1761, "text": "Moreover, these studies show that distressing environmental circumstances can adversely influence neurocognitive dysfunction associated with obesity and diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26163814", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of ibalizumab.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21289125", "http://www.ncbi.nlm.nih.gov/pubmed/29746266", "http://www.ncbi.nlm.nih.gov/pubmed/20698725", "http://www.ncbi.nlm.nih.gov/pubmed/23023102", "http://www.ncbi.nlm.nih.gov/pubmed/25342515", "http://www.ncbi.nlm.nih.gov/pubmed/29989910", "http://www.ncbi.nlm.nih.gov/pubmed/29689540", "http://www.ncbi.nlm.nih.gov/pubmed/19015347", "http://www.ncbi.nlm.nih.gov/pubmed/21134642", "http://www.ncbi.nlm.nih.gov/pubmed/28429756", "http://www.ncbi.nlm.nih.gov/pubmed/30378502", "http://www.ncbi.nlm.nih.gov/pubmed/30110589", "http://www.ncbi.nlm.nih.gov/pubmed/24097413", "http://www.ncbi.nlm.nih.gov/pubmed/24853313", "http://www.ncbi.nlm.nih.gov/pubmed/20463063", "http://www.ncbi.nlm.nih.gov/pubmed/29675744" ], "ideal_answer": [ "Ibalizumab is a humanized monoclonal antibody that acts as post-attachment inhibitor by binding CD4 2nd domain of T lymphocyte and preventing HIV connection to CCR5 or CXCR4. It has been recently approved by Food and Drug Administration as a new intravenous antiretroviral agent for heavily treated HIV adults with multi -drug resistant infection." ], "type": "summary", "id": "5c58b26386df2b9174000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "TaiMed Biologics is developing ibalizumab (Trogarzo\u2122, ibalizumab-uiyk)-a humanised IgG4 monoclonal antibody-as a treatment for HIV-1 infection. Ibalizumab blocks HIV entry into CD4 cells while preserving normal immunological function and is the first CD4-directed post-attachment HIV-1 inhibitor and the first humanised monoclonal antibody for the treatment of HIV/AIDS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29675744", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1338, "text": "Investigational HIV entry inhibitors include the new CD4 attachment inhibitor fostemsavir, which targets HIV envelope glycoprotein 120, and recently approved ibalizumab, which binds the CD4 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29689540", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 378, "text": "Here we review one such agent, ibalizumab, a parenteral CD4 postattachment inhibitor that has demonstrated efficacy as part of combination antiretroviral therapy in the treatment of HIV-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29746266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Trogarzo (ibalizumab-uiyk) is a CD4-directed post-attachment HIV-1 inhibitor, indicated for use with other antiretroviral inhibitors in adults with multidrug resistant HIV-1 infection who aren't responding to their antiretroviral regimen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29989910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "BACKGROUND: Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30110589", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 1136, "text": "RESULTS: Ibalizumab is a new humanized monoclonal antibody. It acts as post-attachment inhibitor by binding CD4 2nd domain of T lymphocyte and preventing HIV connection to CCR5 or CXCR4 and has been recently approved by Food and Drug Administration in the United States of America as a new intravenous antiretroviral agent for heavily treated HIV adults with multi -drug resistant infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30378502", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 798, "text": "Furthermore, we found that a broad neutralizing antibody, ibalizumab, which targets CD4 in the absence of gp120, occupies the same binding surface as the second interface identified here on gp120.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28429756", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 652, "text": "Here we review one such agent, ibalizumab, a parenteral CD4 postattachment inhibitor that has demonstrated efficacy as part of combination antiretroviral therapy in the treatment of HIV-1.
RECENT FINDINGS: In a phase III clinical trial in HIV-infected participants with multiclass antiretroviral drug resistance, the intravenous administration of ibalizumab led to declines in plasma HIV-1 RNA more than 0.5 log in 83% of participants at 1 week.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29746266", "endSection": "abstract" } ] }, { "body": "Describe information obtained by immunophenotyping.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28480599", "http://www.ncbi.nlm.nih.gov/pubmed/28605137", "http://www.ncbi.nlm.nih.gov/pubmed/27749361", "http://www.ncbi.nlm.nih.gov/pubmed/9660728", "http://www.ncbi.nlm.nih.gov/pubmed/28133951" ], "ideal_answer": [ "Mass cytomety enables comprehensive single-cell immunophenotyping and functional assessments, capturing the complexity of the immune system, and the molecularly heterogeneous consequences of primary immunodeficiency defects.\nCirculating B, T, and dendritic cells were defined using flow cytometric analysis as recommended by the Human Immunology Project Consortium.\nClinical applications of flow cytometry currently utilized in the laboratory include cell surface antigen determinations or immunophenotyping of hematologic cells, DNA analysis of hematopoietic malignancies and solid tumors, and measurement of CD4 (T helper/inducer cell) absolute counts and T helper/T suppressor (CD4/CD8) ratios in the evaluation of immune deficiency." ], "type": "summary", "id": "5c5f0d861a4c55d80b000011", "snippets": [ { "offsetInBeginSection": 718, "offsetInEndSection": 825, "text": "both CD4+ absolute counts (cells/\u03bcL) and percentages; and CD8+ absolute counts (cells/\u03bcL) and percentages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28480599", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 351, "text": " Circulating B, T, and dendritic cells were defined using flow cytometric analysis as recommended by the Human Immunology Project Consortium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28605137", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 771, "text": "Mass cytomety enables comprehensive single-cell immunophenotyping and functional assessments, capturing the complexity of the immune system, and the molecularly heterogeneous consequences of primary immunodeficiency defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27749361", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 546, "text": "Clinical applications of flow cytometry currently utilized in the laboratory include cell surface antigen determinations or immunophenotyping of hematologic cells, DNA analysis of hematopoietic malignancies and solid tumors, and measurement of CD4 (T helper/inducer cell) absolute counts and T helper/T suppressor (CD4/CD8) ratios in the evaluation of immune deficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9660728", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 202, "text": " The workup of lymphoproliferative disorders (LPDs) involves the combined use of flow cytometry (FC) and immunohistochemistry (IHC). This often results in duplicate immunophenotypic testing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28133951", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Emicizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27405674", "http://www.ncbi.nlm.nih.gov/pubmed/29769259", "http://www.ncbi.nlm.nih.gov/pubmed/27223146", "http://www.ncbi.nlm.nih.gov/pubmed/29734520", "http://www.ncbi.nlm.nih.gov/pubmed/30264916", "http://www.ncbi.nlm.nih.gov/pubmed/28451690", "http://www.ncbi.nlm.nih.gov/pubmed/29042366", "http://www.ncbi.nlm.nih.gov/pubmed/29296836", "http://www.ncbi.nlm.nih.gov/pubmed/29357074", "http://www.ncbi.nlm.nih.gov/pubmed/30125997", "http://www.ncbi.nlm.nih.gov/pubmed/28691557", "http://www.ncbi.nlm.nih.gov/pubmed/30462521", "http://www.ncbi.nlm.nih.gov/pubmed/30344994", "http://www.ncbi.nlm.nih.gov/pubmed/29888855", "http://www.ncbi.nlm.nih.gov/pubmed/29214439", "http://www.ncbi.nlm.nih.gov/pubmed/30278802", "http://www.ncbi.nlm.nih.gov/pubmed/27384849", "http://www.ncbi.nlm.nih.gov/pubmed/29645406", "http://www.ncbi.nlm.nih.gov/pubmed/30431213", "http://www.ncbi.nlm.nih.gov/pubmed/30444568" ], "ideal_answer": [ "Emicizumab (Hemlibra\u00ae) is a bispecific humanized monoclonal antibody that restores the function of missing activated FVIII by bridging activated FIX and FX to facilitate effective haemostasis in patients with haemophilia A." ], "type": "summary", "id": "5c58a92386df2b917400000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Emicizumab-kxwh (Hemlibra\u00ae) is a bispecific humanized monoclonal antibody that restores the function of missing activated FVIII by bridging activated FIX and FX to facilitate effective haemostasis in patients with haemophilia A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29357074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "BACKGROUND: Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29214439", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 501, "text": "UMMARY: Background Emicizumab is an anti-activated factor\u00a0IX/FX bispecific antibody that mimics activated FVIII cofactor function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29645406", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 574, "text": "Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase 3 trial in people with hemophilia A and inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29769259", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 539, "text": "SUMMARY: Background Emicizumab is an anti-factor (F)IXa/X bispecific monoclonal antibody (mAb), mimicking the factor (F)VIIIa cofactor activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29734520", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 277, "text": " Safety concerns may exist when combining emicizumab with bypassing agents. Combined bypassing agent and bispecific antibody increased thrombin generation up to 17-fold. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29888855", "endSection": "abstract" } ] }, { "body": "What is the genetic cause of Roberts syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26729373", "http://www.ncbi.nlm.nih.gov/pubmed/29084713", "http://www.ncbi.nlm.nih.gov/pubmed/26710928", "http://www.ncbi.nlm.nih.gov/pubmed/28934466", "http://www.ncbi.nlm.nih.gov/pubmed/28422453" ], "ideal_answer": [ "Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2." ], "exact_answer": [ "Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2." ], "type": "factoid", "id": "5ad35d01133db5eb78000003", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 318, "text": " Mutations in Esco2 cause Roberts syndrome, a developmental disease characterized by severe prenatal retardation as well as limb and facial abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28934466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Genetic mapping studies reveal that mutations in cohesion pathways are responsible for multispectrum developmental abnormalities termed cohesinopathies. These include Roberts syndrome (RBS),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28422453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Roberts syndrome and SC phocomelia syndrome are rare autosomal recessive genetic disorders representing the extremes of the spectrum of severity of the same condition, caused by mutations in ESCO2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26710928", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 128, "text": " Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26729373", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 700, "text": "RBS arises due to autosomal recessive mutations in cohesin auxiliary factorESCO2, the gene that encodes an N-acetyltransferase which targets the SMC3 subunit of the cohesin complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29084713", "endSection": "abstract" } ] }, { "body": "What is DiseaseEnhancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29059320" ], "ideal_answer": [ "DiseaseEnhancer is a manually curated resource of human disease-associated enhancer catalog. As of July 2017, DiseaseEnhancer includes 847 disease-associated enhancers in 143 human diseases. Database features include basic enhancer information (i.e. genomic location and target genes); disease types; associated variants on the enhancer and their mediated phenotypes (i.e. gain/loss of enhancer and the alterations of transcription factor bindings)." ], "type": "summary", "id": "5c54600207647bbc4b000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "DiseaseEnhancer: a resource of human disease-associated enhancer catalog.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059320", "endSection": "title" }, { "offsetInBeginSection": 346, "offsetInEndSection": 946, "text": " To facilitate better usage of published data and exploring enhancer deregulation in various human diseases, we created DiseaseEnhancer (http://biocc.hrbmu.edu.cn/DiseaseEnhancer/), a manually curated database for disease-associated enhancers. As of July 2017, DiseaseEnhancer includes 847 disease-associated enhancers in 143 human diseases. Database features include basic enhancer information (i.e. genomic location and target genes); disease types; associated variants on the enhancer and their mediated phenotypes (i.e. gain/loss of enhancer and the alterations of transcription factor bindings).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059320", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1264, "text": "DiseaseEnhancer provides a promising avenue for researchers to facilitate the understanding of enhancer deregulation in disease pathogenesis, and identify new biomarkers for disease diagnosis and therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059320", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 589, "text": "To facilitate better usage of published data and exploring enhancer deregulation in various human diseases, we created DiseaseEnhancer (http://biocc.hrbmu.edu.cn/DiseaseEnhancer/), a manually curated database for disease-associated enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059320", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 687, "text": "As of July 2017, DiseaseEnhancer includes 847 disease-associated enhancers in 143 human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059320", "endSection": "abstract" } ] }, { "body": "Is Tisagenlecleucel effective for B-Cell Lymphoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30190371", "http://www.ncbi.nlm.nih.gov/pubmed/29247018", "http://www.ncbi.nlm.nih.gov/pubmed/29385370", "http://www.ncbi.nlm.nih.gov/pubmed/30213399", "http://www.ncbi.nlm.nih.gov/pubmed/30111196", "http://www.ncbi.nlm.nih.gov/pubmed/30501490", "http://www.ncbi.nlm.nih.gov/pubmed/29914976", "http://www.ncbi.nlm.nih.gov/pubmed/30309857", "http://www.ncbi.nlm.nih.gov/pubmed/29499750", "http://www.ncbi.nlm.nih.gov/pubmed/29451276" ], "ideal_answer": [ "Yes, CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma." ], "exact_answer": "yes", "type": "yesno", "id": "5c56033607647bbc4b00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The phase II JULIET trial suggests that the CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29247018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385370", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385370", "endSection": "abstract" }, { "offsetInBeginSection": 1676, "offsetInEndSection": 1943, "text": "CONCLUSIONS: In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Chimeric antigen receptor T cells demonstrate efficacy in B-cell malignancies, leading to US Food and Drug Administration approval of axicabtagene ciloleucel (October 2017) and tisagenlecleucel (May 2018) for large B-cell lymphomas after 2 prior lines of therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29914976", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 605, "text": "This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29914976", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 609, "text": "This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29914976", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 698, "text": "The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
METHODS: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30501490", "endSection": "abstract" }, { "offsetInBeginSection": 1818, "offsetInEndSection": 2154, "text": "No differences between response groups in tumor expression of CD19 or immune checkpoint-related proteins were found.
CONCLUSIONS: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30501490", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 463, "text": "This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451276", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 593, "text": "Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug Administration for the treatment of relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy based on multicenter single-arm phase two clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213399", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 382, "text": "On August 30, 2017, the U.S. Food and Drug Administration approved tisagenlecleucel for treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30309857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30111196", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30190371", "endSection": "abstract" } ] }, { "body": "What is the function of GFRAL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28846097", "http://www.ncbi.nlm.nih.gov/pubmed/28953886", "http://www.ncbi.nlm.nih.gov/pubmed/29129392", "http://www.ncbi.nlm.nih.gov/pubmed/28846098", "http://www.ncbi.nlm.nih.gov/pubmed/28846099" ], "ideal_answer": [ "GFRAL (orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor \u03b1 family) is a high-affinity receptor for GDF15.\nGFRAL expression is limited to hindbrain neurons and not present in peripheral tissues, which suggests that GDF15-GFRAL-mediated regulation of food intake is by a central mechanism." ], "type": "summary", "id": "5ad3072a0340b9f05800001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846097", "endSection": "title" }, { "offsetInBeginSection": 595, "offsetInEndSection": 799, "text": "We further found that GFRAL expression was limited to hindbrain neurons and not present in peripheral tissues, which suggests that GDF15-GFRAL-mediated regulation of food intake is by a central mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846099", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1020, "text": " Here we report that GDNF-family receptor \u03b1-like (GFRAL), an orphan member of the GFR-\u03b1 family, is a high-affinity receptor for GDF15.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28846098", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 818, "text": "Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptor for growth and differentiation factor 15 (GDF15).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28953886", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 500, "text": "Four laboratories have recently identified GFRAL, an orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor \u03b1 family, as the receptor for MIC-1/GDF15, signaling though the coreceptor Ret. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29129392", "endSection": "abstract" } ] }, { "body": "What is the role of ZCCHC17?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26202100", "http://www.ncbi.nlm.nih.gov/pubmed/29028963" ], "ideal_answer": [ "ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease. Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. Its loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets." ], "type": "summary", "id": "5c6d7ff87c78d6947100003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 961, "text": "In an effort to better understand the molecular drivers of synaptic and neurophysiologic dysfunction in Alzheimer's disease (AD), we analyzed neuronal gene expression data from human AD brain tissue to identify master regulators of synaptic gene expression.Results: Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats. These findings support a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an important early driver of lower synaptic gene expression in AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 592, "text": "We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 479, "text": "Results\nMaster regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 794, "text": "We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 962, "text": "These findings support a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an important early driver of lower synaptic gene expression in AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1273, "text": "We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26202100", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 479, "text": "Results Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 811, "text": "We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 1258, "text": "These findings support a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an important early driver of lower synaptic gene expression in AD.
Availability and implementation: Matlab and R scripts used in this paper are available at https://github.com/afteich/AD_ZCC.
Contact: aft25@cumc.columbia.edu.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 609, "text": "We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028963", "endSection": "abstract" } ] }, { "body": "Is ADP-ribosylation a PTM?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29327913", "http://www.ncbi.nlm.nih.gov/pubmed/29172462", "http://www.ncbi.nlm.nih.gov/pubmed/29554239" ], "ideal_answer": [ "Yes,\nPoly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses." ], "exact_answer": "yes", "type": "yesno", "id": "5c76cea17c78d694710000a7", "snippets": [ { "offsetInBeginSection": 84, "offsetInEndSection": 230, "text": "ADP-ribosylation is a PTM, in which ADP-ribosyltransferases use nicotinamide adenine dinucleotide (NAD+) to modify target proteins with ADP-ribose", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29172462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29327913", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 224, "text": "ADP-ribosylation is a post-translational modification (PTM) implicated in several crucial cellular processes, ranging from regulation of DNA repair and chromatin structure to cell metabolism and stress responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554239", "endSection": "abstract" } ] }, { "body": "Does epidural anesthesia for pain management during labor affect the Apgar score of the the infant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28013485", "http://www.ncbi.nlm.nih.gov/pubmed/19466346" ], "ideal_answer": [ "Epidural analgesia for labor pain management did not appear to have an immediate effect on neonatal status as determined by Apgar scores or in admissions to neonatal intensive care." ], "exact_answer": "no", "type": "yesno", "id": "5c56fd7407647bbc4b000013", "snippets": [ { "offsetInBeginSection": 295, "offsetInEndSection": 1122, "text": " We retrospectively analyzed 93 consecutive single-pregnancy patients who underwent cesarean section with combined spinal-epidural anesthesia. The patients were divided into two groups, depending on the use of 6% HES 130/0.4: group A (461\u00a0\u00b1\u00a0167\u00a0ml of saline-based HES was administered; 43 patients) and group B (HES not administered; 50 patients). The major outcome was umbilical cord chloride level at delivery. The volume infused from operating room admission until delivery was not significantly different between groups. The umbilical cord chloride level at delivery was statistically significantly higher in group A than in group B, but clinically similar (108\u00a0\u00b1\u00a02 vs. 107\u00a0\u00b1\u00a02\u00a0mmol/l, P\u00a0=\u00a00.02). No differences were observed in the Apgar score or other umbilical cord laboratory data at delivery (Na+, K+, pH, base excess)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28013485", "endSection": "abstract" }, { "offsetInBeginSection": 1845, "offsetInEndSection": 2057, "text": "CONCLUSION\nSubarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19466346", "endSection": "abstract" }, { "offsetInBeginSection": 1845, "offsetInEndSection": 2057, "text": "CONCLUSION Subarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19466346", "endSection": "abstract" } ] }, { "body": "What is latex bead phagocytosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18687123", "http://www.ncbi.nlm.nih.gov/pubmed/16612292", "http://www.ncbi.nlm.nih.gov/pubmed/8262564" ], "ideal_answer": [ "Macrophage scavenger function was assessed by an in vitro latex bead phagocytosis assay.\nWe developed a scanning cytometry-based high-throughput assay of macrophage phagocytosis that quantitates bound and internalized unopsonized latex beads." ], "type": "summary", "id": "5c76e20f7c78d694710000ab", "snippets": [ { "offsetInBeginSection": 1051, "offsetInEndSection": 1139, "text": "macrophage scavenger function was assessed by an in vitro latex bead phagocytosis assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16612292", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 638, "text": " We developed a scanning cytometry-based high-throughput assay of macrophage phagocytosis that quantitates bound and internalized unopsonized latex beads. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687123", "endSection": "abstract" }, { "offsetInBeginSection": 571, "offsetInEndSection": 961, "text": "For the phagocytic assay, fluorescein conjugated polystyrene beads were incubated with macrophage monolayers in white luminostrips. After incubation, cells were washed, lysed and phagocytosis quantified by determining the fluorescent intensity using a fluorescence plate reader. The number of beads phagocytized was determined from a standard curve of bead number versus fluorescent output.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8262564", "endSection": "abstract" } ] }, { "body": "Is phospholipid hydroperoxide glutathione peroxidase a selenoprotein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29502249", "http://www.ncbi.nlm.nih.gov/pubmed/25922076", "http://www.ncbi.nlm.nih.gov/pubmed/24795696" ], "ideal_answer": [ "Yes,\nthe phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) is the major selenoprotein." ], "exact_answer": "yes", "type": "yesno", "id": "5c5f22951a4c55d80b00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Glutathione peroxidase (Gpx1) is the major selenoprotein in most tissues in animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29502249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25922076", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1081, "text": "the major selenoprotein expressed by germ cells in the testis, the phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24795696", "endSection": "abstract" } ] }, { "body": "Describe CGmapTools", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28968643" ], "ideal_answer": [ "CGmapTools improves the precision of heterozygous SNV calls and supports allele-specific methylation detection and visualization in bisulfite-sequencing data.", "DNA methylation is important for gene silencing and imprinting in both plants and animals. Recent advances in bisulfite sequencing allow detection of single nucleotide variations (SNVs) achieving high sensitivity, but accurately identifying heterozygous SNVs from partially C-to-T converted sequences remains challenging. CGmapTools is a software package that integrates 40 applications with the aim to analyze DNA methylomes. This package uses CGmap as the format interface, and designs binary formats to reduce the file size and support fast data retrieval, and can be applied for context-wise, gene-wise, bin-wise, region-wise and sample-wise analyses and visualizations." ], "type": "summary", "id": "5c6d88257c78d6947100003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "CGmapTools improves the precision of heterozygous SNV calls and supports allele-specific methylation detection and visualization in bisulfite-sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968643", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1566, "text": "DNA methylation is important for gene silencing and imprinting in both plants and animals. Recent advances in bisulfite sequencing allow detection of single nucleotide variations (SNVs) achieving high sensitivity, but accurately identifying heterozygous SNVs from partially C-to-T converted sequences remains challenging.Results: We designed two methods, BayesWC and BinomWC, that substantially improved the precision of heterozygous SNV calls from \u223c80% to 99% while retaining comparable recalls. With these SNV calls, we provided functions for allele-specific DNA methylation (ASM) analysis and visualizing the methylation status on reads. Applying ASM analysis to a previous dataset, we found that an average of 1.5% of investigated regions showed allelic methylation, which were significantly enriched in transposon elements and likely to be shared by the same cell-type. A dynamic fragment strategy was utilized for DMR analysis in low-coverage data and was able to find differentially methylated regions (DMRs) related to key genes involved in tumorigenesis using a public cancer dataset. Finally, we integrated 40 applications into the software package CGmapTools to analyze DNA methylomes. This package uses CGmap as the format interface, and designs binary formats to reduce the file size and support fast data retrieval, and can be applied for context-wise, gene-wise, bin-wise, region-wise and sample-wise analyses and visualizations.Availability and implementation: The CGmapTools software is freely available at https://cgmaptools.github.io/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968643", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1209, "text": "Finally, we integrated 40 applications into the software package CGmapTools to analyze DNA methylomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968643", "endSection": "abstract" }, { "offsetInBeginSection": 1322, "offsetInEndSection": 1424, "text": "Finally, we integrated 40 applications into the software package CGmapTools to analyze DNA methylomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968643", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1226, "text": "Finally, we integrated 40 applications into the software package CGmapTools to analyze DNA methylomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968643", "endSection": "abstract" }, { "offsetInBeginSection": 1227, "offsetInEndSection": 1737, "text": "This package uses CGmap as the format interface, and designs binary formats to reduce the file size and support fast data retrieval, and can be applied for context-wise, gene-wise, bin-wise, region-wise and sample-wise analyses and visualizations.
Availability and implementation: The CGmapTools software is freely available at https://cgmaptools.github.io/.
Contact: guoweilong@cau.edu.cn.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968643", "endSection": "abstract" } ] }, { "body": "Is inositol effective for trichotillomania?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28183072", "http://www.ncbi.nlm.nih.gov/pubmed/27824633" ], "ideal_answer": [ "No, inositol is not effective for trichotillomania" ], "exact_answer": "no", "type": "yesno", "id": "5c73aced7c78d69471000087", "snippets": [ { "offsetInBeginSection": 823, "offsetInEndSection": 978, "text": "Patients assigned to inositol failed to show significantly greater reductions on primary or secondary outcomes measures compared with placebo (all P>0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824633", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1267, "text": "This is the first study assessing the efficacy of inositol in the treatment of trichotillomania, but found no differences in symptom reductions between inositol and placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824633", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1093, "text": "At study endpoint, 42.1% of patients were 'much or very much improved' on inositol compared with 35.3% on placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824633", "endSection": "abstract" }, { "offsetInBeginSection": 2873, "offsetInEndSection": 3135, "text": "Conclusions \u2022 The review indicates that yoga, aerobic exercise, acupuncture, biofeedback, hypnosis, and inositol and N-acetylcysteine all show promise in the treatment of excoriation disorder and other body-focused repetitive behaviors, such as trichotillomania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28183072", "endSection": "abstract" }, { "offsetInBeginSection": 1348, "offsetInEndSection": 1496, "text": "Future studies should examine whether inositol may be beneficial in controlling pulling behavior in a subgroup of individuals with trichotillomania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824633", "endSection": "abstract" } ] }, { "body": "How is the Regulatory Trait Concordance (RTC) calculated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25453756", "http://www.ncbi.nlm.nih.gov/pubmed/10221642", "http://www.ncbi.nlm.nih.gov/pubmed/29058715", "http://www.ncbi.nlm.nih.gov/pubmed/29059182", "http://www.ncbi.nlm.nih.gov/pubmed/20369022" ], "ideal_answer": [ "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs.", "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. After stringently testing for a shared causal variant using both the Joint Likelihood Mapping and Regulatory Trait Concordance frameworks, we found that gene-level quantification significantly underestimated the number of causal cis-eQTLs.", "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. After stringently testing for a shared causal variant using both the Joint Likelihood Mapping and Regulatory Trait Concordance frameworks, we found that gene-level quantification significantly underestimated the number of causal cis-eQTLs. We have adapted the regulatory trait concordance (RTC) score to measure the probability of eQTLs being active in multiple tissues and to calculate the probability that a GWAS-associated variant and an eQTL tag the same functional effect.", "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. We have adapted the regulatory trait concordance (RTC) score to measure the probability of eQTLs being active in multiple tissues and to calculate the probability that a GWAS-associated variant and an eQTL tag the same functional effect." ], "type": "summary", "id": "5c70001f7c78d6947100005c", "snippets": [ { "offsetInBeginSection": 591, "offsetInEndSection": 781, "text": "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20369022", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1042, "text": "After stringently testing for a shared causal variant using both the Joint Likelihood Mapping and Regulatory Trait Concordance frameworks, we found that gene-level quantification significantly underestimated the number of causal cis-eQTLs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059182", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 738, "text": "We have adapted the regulatory trait concordance (RTC) score to measure the probability of eQTLs being active in multiple tissues and to calculate the probability that a GWAS-associated variant and an eQTL tag the same functional effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058715", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 780, "text": "In the present study, we propose an empirical methodology, which we call Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20369022", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 800, "text": "We have adapted the regulatory trait concordance (RTC) score to measure the probability of eQTLs being active in multiple tissues and to calculate the probability that a GWAS-associated variant and an eQTL tag the same functional effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29058715", "endSection": "abstract" } ] }, { "body": "What is filipin staining used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28859904", "http://www.ncbi.nlm.nih.gov/pubmed/29197565", "http://www.ncbi.nlm.nih.gov/pubmed/30258093", "http://www.ncbi.nlm.nih.gov/pubmed/29845234", "http://www.ncbi.nlm.nih.gov/pubmed/30093524" ], "ideal_answer": [ "Intracellular and total cholesterol (TC) were measured using filipin staining." ], "type": "summary", "id": "5c76d31c7c78d694710000a9", "snippets": [ { "offsetInBeginSection": 538, "offsetInEndSection": 628, "text": "sequestration of cholesterol to the perinuclear area, as evident by the Filipin staining. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28859904", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 512, "text": "Current diagnosis for NP-C is based on observation of the accumulated cholesterol in fibroblasts of affected individuals, using an invasive and time expensive test, called Filipin staining. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29197565", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 778, "text": " Membrane cholesterol content was measured by filipin staining ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30093524", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 853, "text": "intracellular and total cholesterol (TC) were measured using filipin staining", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29845234", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1088, "text": " filipin staining of cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30258093", "endSection": "abstract" } ] }, { "body": "Is TIAM1 favoring tumor progression in colorectal cancer (CRC)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28416184", "http://www.ncbi.nlm.nih.gov/pubmed/17132223" ], "ideal_answer": [ "No. In colorectal cancer (CRC) TIAM1 suppresses tumor progression by regulating YAP/TAZ activity." ], "exact_answer": "no", "type": "yesno", "id": "5c640fa1e842deac67000011", "snippets": [ { "offsetInBeginSection": 55, "offsetInEndSection": 906, "text": "Here, we identify TIAM1 as a critical antagonist of CRC progression through inhibiting TAZ and YAP, effectors of WNT signaling. We demonstrate that TIAM1 shuttles between the cytoplasm and nucleus antagonizing TAZ/YAP by distinct mechanisms in the two compartments. In the cytoplasm, TIAM1 localizes to the destruction complex and promotes TAZ degradation by enhancing its interaction with \u03b2TrCP. Nuclear TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP target genes implicated in epithelial-mesenchymal transition, cell migration, and invasion, and consequently suppresses CRC cell migration and invasion. Importantly, high nuclear TIAM1 in clinical specimens associates with increased CRC patient survival. Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP/TAZ activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416184", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 906, "text": "Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP/TAZ activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416184", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 694, "text": "Nuclear TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP target genes implicated in epithelial-mesenchymal transition, cell migration, and invasion, and consequently suppresses CRC cell migration and invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416184", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 898, "text": "Using an orthotopic xenograft model in nude mice, we confirmed that Tiam1 silencing could reduce tumor growth by subcutaneous injection and could suppress lung and liver metastases of colorectal cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17132223", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 910, "text": "Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP/TAZ activity.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416184", "endSection": "abstract" } ] }, { "body": "Which database has been developed that contains experimentally-confirmed carbonylated proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29509874" ], "ideal_answer": [ "Protein carbonylation, a chemically diverse oxidative post-translational modification, is widely considered as the biomarker for oxidative stress and protein damage. CarbonylDB has been developed as a manually curated data-resource of experimentally-confirmed carbonylated proteins/sites. The CarbonylDB currently contains 1495 carbonylated proteins and 3781 sites from 21 species, with human, rat and yeast as the top three species." ], "exact_answer": [ "CarbonylDB" ], "type": "factoid", "id": "5c6be8f07c78d69471000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "CarbonylDB: a curated data-resource of protein carbonylation sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "title" }, { "offsetInBeginSection": 163, "offsetInEndSection": 1046, "text": "Protein carbonylation, a chemically diverse oxidative post-translational modification, is widely considered as the biomarker for oxidative stress and protein damage. Despite their importance and extensive studies, no database/resource on carbonylated proteins/sites exists. As such information is very useful to research in biology/medicine, we have manually curated a data-resource (CarbonylDB) of experimentally-confirmed carbonylated proteins/sites.Results: The CarbonylDB currently contains 1495 carbonylated proteins and 3781 sites from 21 species, with human, rat and yeast as the top three species. We have made further analyses of these carbonylated proteins/sites and presented their occurrence and occupancy patterns. Carbonylation site data on serum albumin, in particular, provides a fine model system to understand the dynamics of oxidative protein modifications/damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 614, "text": "As such information is very useful to research in biology/medicine, we have manually curated a data-resource (CarbonylDB) of experimentally-confirmed carbonylated proteins/sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 769, "text": "Results\nThe CarbonylDB currently contains 1495 carbonylated proteins and 3781 sites from 21 species, with human, rat and yeast as the top three species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 769, "text": "Results The CarbonylDB currently contains 1495 carbonylated proteins and 3781 sites from 21 species, with human, rat and yeast as the top three species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 703, "text": "As such information is very useful to research in biology/medicine, we have manually curated a data-resource (CarbonylDB) of experimentally-confirmed carbonylated proteins/sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 786, "text": "As such information is very useful to research in biology/medicine, we have manually curated a data-resource (CarbonylDB) of experimentally-confirmed carbonylated proteins/sites.
Results: The CarbonylDB currently contains 1495 carbonylated proteins and 3781 sites from 21 species, with human, rat and yeast as the top three species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1313, "text": "Carbonylation site data on serum albumin, in particular, provides a fine model system to understand the dynamics of oxidative protein modifications/damage.
Availability and implementation: The CarbonylDB is available as a web-resource and for download at http://digbio.missouri.edu/CarbonylDB/.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29509874", "endSection": "abstract" } ] }, { "body": "What is the function of the Nup153 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16133350", "http://www.ncbi.nlm.nih.gov/pubmed/25485891", "http://www.ncbi.nlm.nih.gov/pubmed/28513807", "http://www.ncbi.nlm.nih.gov/pubmed/15659641", "http://www.ncbi.nlm.nih.gov/pubmed/28751496", "http://www.ncbi.nlm.nih.gov/pubmed/22075984", "http://www.ncbi.nlm.nih.gov/pubmed/8794857", "http://www.ncbi.nlm.nih.gov/pubmed/10671368" ], "ideal_answer": [ "Nup153 is a large (153 kD) O-linked glyco-protein which is a component of the basket structure located on the nucleoplasmic face of nuclear pore complexes. Nup153 is a nucleoporin mediating nuclear import. In addition to being important to pore architecture, Nup153 is a key participant in both import and export. During the transition into mitosis, Nup153 directs proteins involved in membrane remodeling to the nuclear envelope." ], "type": "summary", "id": "5c6585097c78d69471000003", "snippets": [ { "offsetInBeginSection": 80, "offsetInEndSection": 128, "text": "Nup153 to reforming functional nuclear envelopes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10671368", "endSection": "title" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1156, "text": "Taken together, these results showed that emerin, LBR, and several NPC components (RanBP2, Nup153, p62), but not Tpr, reconstitute around chromosomes very early in telophase prior to the recovery of nuclear import activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10671368", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 486, "text": "On the basis of protein domain similarity, the human nucleoporin Nup153 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15659641", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 110, "text": "human Nup153 mediate nuclear import", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15659641", "endSection": "title" }, { "offsetInBeginSection": 81, "offsetInEndSection": 187, "text": "In addition to being important to pore architecture, Nup153 is a key participant in both import and export", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16133350", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 411, "text": "During the transition into mitosis, Nup153 directs proteins involved in membrane remodeling to the nuclear envelope.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16133350", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 909, "text": "Overall, the versatile nature of Nup153 underscores an emerging view of the nuclear pore at the nexus of many key cellular processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16133350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075984", "endSection": "title" }, { "offsetInBeginSection": 516, "offsetInEndSection": 613, "text": "a nuclear pore component NUP153 as a novel factor specifically required for 53BP1 nuclear import.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075984", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 475, "text": " The nuclear basket is composed of the 3 nucleoporins Nup153, Nup50, and Tpr, but their specific role for the structural organization of this NPC substructure is, however, not well established", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25485891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The nuclear pore protein Nup153 associates with chromatin and regulates cardiac gene expression in dystrophic mdx hearts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28513807", "endSection": "title" }, { "offsetInBeginSection": 404, "offsetInEndSection": 534, "text": "The nucleoporin Nup153 has been implicated in the DNA damage response, attributed to a role in promoting nuclear import of 53BP1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28751496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Nup153 is a large (153 kD) O-linked glyco-protein which is a component of the basket structure located on the nucleoplasmic face of nuclear pore complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8794857", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 188, "text": "In addition to being important to pore architecture, Nup153 is a key participant in both import and export.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16133350", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1230, "text": "Finally, we show that the C-terminal part of NUP153 is required for effective 53BP1 nuclear import, and that 53BP1 is imported to the nucleus through the NUP153-importin-\u03b2 interplay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075984", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1405, "text": "Our data define the structure-function relationships within this emerging 53BP1-NUP153/importin-\u03b2 pathway and implicate this mechanism in the maintenance of genome integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075984", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 613, "text": "Here, we provide the complete results of this screen as an information resource, and validate and functionally characterize one of the identified 'hits': a nuclear pore component NUP153 as a novel factor specifically required for 53BP1 nuclear import.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22075984", "endSection": "abstract" } ] }, { "body": "Is pacritinib effective for treatment of myelofibrosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29562644", "http://www.ncbi.nlm.nih.gov/pubmed/29650801", "http://www.ncbi.nlm.nih.gov/pubmed/29522138", "http://www.ncbi.nlm.nih.gov/pubmed/26288713", "http://www.ncbi.nlm.nih.gov/pubmed/29235894", "http://www.ncbi.nlm.nih.gov/pubmed/26367195", "http://www.ncbi.nlm.nih.gov/pubmed/25762180", "http://www.ncbi.nlm.nih.gov/pubmed/28441920", "http://www.ncbi.nlm.nih.gov/pubmed/30001163", "http://www.ncbi.nlm.nih.gov/pubmed/29616317", "http://www.ncbi.nlm.nih.gov/pubmed/26389774", "http://www.ncbi.nlm.nih.gov/pubmed/27931243", "http://www.ncbi.nlm.nih.gov/pubmed/27226728", "http://www.ncbi.nlm.nih.gov/pubmed/24746271", "http://www.ncbi.nlm.nih.gov/pubmed/29785143", "http://www.ncbi.nlm.nih.gov/pubmed/28336242" ], "ideal_answer": [ "Yes. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in myelofibrosis with minimal myelosuppression." ], "exact_answer": "yes", "type": "yesno", "id": "5c663afe7c78d69471000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29235894", "endSection": "title" }, { "offsetInBeginSection": 490, "offsetInEndSection": 736, "text": "Pacritinib, a dual JAK2 and FLT3 inhibitor which also inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated splenomegaly and symptom burden, while having limited myelosuppression with manageable gastrointestinal toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29235894", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 631, "text": "Other JAKis, such as fedratinib and pacritinib, proved to be useful in MF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29650801", "endSection": "abstract" }, { "offsetInBeginSection": 2640, "offsetInEndSection": 2879, "text": "Conclusions and Relevance: In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522138", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1308, "text": "Developments of JAK inhibitors, such as ruxolitinib, pacritinib, momelotinib, and febratinib enabled the effective management in MF patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562644", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 507, "text": " Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29616317", "endSection": "abstract" }, { "offsetInBeginSection": 2714, "offsetInEndSection": 2869, "text": "Pacritinib could be a treatment option for patients with myelofibrosis, including those with baseline cytopenias for whom options are particularly limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28336242", "endSection": "abstract" }, { "offsetInBeginSection": 2652, "offsetInEndSection": 2890, "text": "Conclusions and Relevance\nIn patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522138", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 970, "text": "Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30001163", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 673, "text": "Pacritinib, a dual JAK2 and FLT3 inhibitor, improves disease-related symptoms and signs with manageable gastrointestinal toxicity in patients with myelofibrosis with splenomegaly and high-risk features, without causing overt myelosuppression, and therefore may provide an important treatment option for a range of patients with myelofibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26367195", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1349, "text": "Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25762180", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 506, "text": "Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29616317", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 905, "text": "This article examines the role of JAK2 and FLT3 signaling in myelofibrosis and provides an overview of the clinical development of pacritinib as a new therapy for myelofibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26367195", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1574, "text": "Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26389774", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 991, "text": "Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30001163", "endSection": "abstract" } ] }, { "body": "How can PEGylation improve recombinant drugs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24855821" ], "ideal_answer": [ "PEGylation primarily improves pharmacokinetics and helps to prevent adverse drug reactions, by increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes." ], "type": "summary", "id": "5c66d6167c78d69471000018", "snippets": [ { "offsetInBeginSection": 541, "offsetInEndSection": 735, "text": "By increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes, PEGylation primarily improves pharmacokinetics and helps to prevent adverse drug reactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24855821", "endSection": "abstract" } ] }, { "body": "Can exposure to heavy metals like lead(Pb) or cadmium(Cd) cause changes in DNA methylation patterns in Isoetes sinensis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29053963", "http://www.ncbi.nlm.nih.gov/pubmed/30515690" ], "ideal_answer": [ "Changes in DNA methylation of the endangered plant, Isoetes sinensis, have be shown to be affected by both Pb and Cd" ], "exact_answer": "yes", "type": "yesno", "id": "5c571f7607647bbc4b000017", "snippets": [ { "offsetInBeginSection": 108, "offsetInEndSection": 315, "text": "DNA methylation in endangered plants after exposure to heavy metals, the Isoetes sinensis, an endangered plant, was stressed with three different concentrations of two heavy metals lead (Pb) and cadmium (Cd)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515690", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 596, "text": "The results showed that the DNA methylated profile of I. sinensis was affected by Pb and Cd stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515690", "endSection": "abstract" }, { "offsetInBeginSection": 1372, "offsetInEndSection": 1592, "text": "The proportion of DNA methylation (including hypermethylation) by both Pb and Cd stresses is nearly equal (39.04% and 39.71%), but the proportion of DNA demethylation by Cd is higher than that by Pb (46.86% than 33.92%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515690", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 766, "text": "There was no significant difference in the amount of DNA methylation among control check (CK), Pb stress group, and Cd stress group (CK 46.96%, Pb 48.23%, and Cd 48.1%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515690", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 1013, "text": "However, full-methylation level of Pb stress group (28.34%) and Cd stress group (20.25%) was lower than control (33.91%), in contrast, hemi-methylation level Pb stress group (19.89%) and Cd stress group (27.85%) were higher than control (13.04%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515690", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 752, "text": "Consistently, a dramatic change in DNA methylation patterns was detected in excess Cu-exposed H. verticillata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29053963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Hydrilla verticillata employs two different ways to affect DNA methylation under excess copper stress.Because of the accumulation of heavy metals, Hydrilla verticillata (L.f.) Royle, a rooted submerged perennial aquatic herb, is being developed as a potential tool to clean the aquatic ecosystem polluted by heavy metals. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29053963", "endSection": "title" }, { "offsetInBeginSection": 1372, "offsetInEndSection": 1596, "text": "The proportion of DNA methylation (including hypermethylation) by both Pb and Cd stresses is nearly equal (39.04% and 39.71%), but the proportion of DNA demethylation by Cd is higher than that by Pb (46.86% than 33.92%).
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515690", "endSection": "abstract" } ] }, { "body": "Describe GeneCodeq", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27354700" ], "ideal_answer": [ "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy. Its model leverages a corpus of k-mers to reduce the entropy of the quality scores and thereby the compressibility of these data (in FASTQ or SAM/BAM/CRAM files), resulting in compression ratios that significantly exceeds those of other methods. GeneCodeq can be combined with existing lossy compression schemes to further reduce entropy and allows the user to specify a reference panel of expected sequence variations to improve the model accuracy." ], "type": "summary", "id": "5c6d8b237c78d6947100003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "GeneCodeq: quality score compression and improved genotyping using a Bayesian framework.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1574, "text": "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses.RESULTS: We here propose GeneCodeq, a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy. Our model leverages a corpus of k-mers to reduce the entropy of the quality scores and thereby the compressibility of these data (in FASTQ or SAM/BAM/CRAM files), resulting in compression ratios that significantly exceeds those of other methods. Our approach can also be combined with existing lossy compression schemes to further reduce entropy and allows the user to specify a reference panel of expected sequence variations to improve the model accuracy. In addition to extensive empirical evaluation, we also derive novel theoretical insights that explain the empirical performance and pitfalls of corpus-based quality score compression schemes in general. Finally, we show that as a positive side effect of compression, the model can lead to improved genotyping accuracy.AVAILABILITY AND IMPLEMENTATION: GeneCodeq is available at: github.com/genecodeq/eval", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 713, "text": "RESULTS\nWe here propose GeneCodeq, a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 713, "text": "RESULTS We here propose GeneCodeq, a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 730, "text": "Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses.
RESULTS: We here propose GeneCodeq, a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1718, "text": "Finally, we show that as a positive side effect of compression, the model can lead to improved genotyping accuracy.
AVAILABILITY AND IMPLEMENTATION: GeneCodeq is available at: github.com/genecodeq/eval CONTACT: dan@petagene.comSupplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "abstract" } ] }, { "body": "Has Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) been reported to be a plasminogen receptor in pathogenic bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28011643", "http://www.ncbi.nlm.nih.gov/pubmed/15039372", "http://www.ncbi.nlm.nih.gov/pubmed/17449317", "http://www.ncbi.nlm.nih.gov/pubmed/25666684" ], "ideal_answer": [ "Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been reported to be a plasminogen receptor in many pathogenic bacteria." ], "exact_answer": "yes", "type": "yesno", "id": "5c57031107647bbc4b000014", "snippets": [ { "offsetInBeginSection": 177, "offsetInEndSection": 508, "text": " binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues, and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28011643", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 556, "text": "Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25666684", "endSection": "abstract" }, { "offsetInBeginSection": 1230, "offsetInEndSection": 1339, "text": "Purified GAPDH was found to bind human plasminogen and fibrinogen in Far-Western blot and ELISA-based assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17449317", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 446, "text": "GAPDH exhibits a high affinity for plasmin and a significantly lower affinity for plasminogen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15039372", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 715, "text": "Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25666684", "endSection": "abstract" } ] }, { "body": "Which de novo truncating mutations in WASF1 cause intellectual disability?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29961568" ], "ideal_answer": [ "De novo truncating mutations in WAS protein family member 1 (WASF1) were identified in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling." ], "exact_answer": [ [ "c.1516C>T", "p.Arg506Ter" ], [ "c.1558C>T", "p.Gln520Ter" ], [ "c.1482delinsGCCAGG", "p.Ile494MetfsTer23" ] ], "type": "list", "id": "5c61f379e842deac67000006", "snippets": [ { "offsetInBeginSection": 151, "offsetInEndSection": 1134, "text": "Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de\u00a0novo heterozygous mutations in WASF1 cause a rare form of intellectual disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29961568", "endSection": "abstract" } ] }, { "body": "Can CPX-351 be used for the treatment of tuberculosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29167924" ], "ideal_answer": [ "No, CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML)." ], "exact_answer": "no", "type": "yesno", "id": "5c6549e1e842deac67000022", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 164, "text": "CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167924", "endSection": "abstract" } ] }, { "body": "Which proteins form the nuclear pore basket in human cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11535617", "http://www.ncbi.nlm.nih.gov/pubmed/25602437", "http://www.ncbi.nlm.nih.gov/pubmed/25942622", "http://www.ncbi.nlm.nih.gov/pubmed/17724121", "http://www.ncbi.nlm.nih.gov/pubmed/10806081", "http://www.ncbi.nlm.nih.gov/pubmed/29791854", "http://www.ncbi.nlm.nih.gov/pubmed/23591820", "http://www.ncbi.nlm.nih.gov/pubmed/30366908", "http://www.ncbi.nlm.nih.gov/pubmed/11598013", "http://www.ncbi.nlm.nih.gov/pubmed/25485891", "http://www.ncbi.nlm.nih.gov/pubmed/9348540", "http://www.ncbi.nlm.nih.gov/pubmed/10921874", "http://www.ncbi.nlm.nih.gov/pubmed/11567018", "http://www.ncbi.nlm.nih.gov/pubmed/8794857", "http://www.ncbi.nlm.nih.gov/pubmed/15229283", "http://www.ncbi.nlm.nih.gov/pubmed/11839768", "http://www.ncbi.nlm.nih.gov/pubmed/25845599" ], "ideal_answer": [ "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. Moreover, the association of TREX-2 with the NPC requires the basket nucleoporins NUP153 and TPR, but is independent of transcription. The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins", "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. Here we show that the NPC basket proteins Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion into the lipid bilayer Moreover, the association of TREX-2 with the NPC requires the basket nucleoporins NUP153 and TPR, but is independent of transcription.", "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. The nuclear pore complex basket proteins Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion into the lipid bilayer. The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins.", "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. Here we show that the NPC basket proteins Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion into the lipid bilayer The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins" ], "exact_answer": [ [ "Nup133" ], [ "Nup1" ], [ "Nup60" ], [ "Nup153" ] ], "type": "list", "id": "5c72d4c77c78d6947100007c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29791854", "endSection": "title" }, { "offsetInBeginSection": 350, "offsetInEndSection": 495, "text": "Here we show that the NPC basket proteins Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion into the lipid bilayer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25942622", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 704, "text": "Moreover, the association of TREX-2 with the NPC requires the basket nucleoporins NUP153 and TPR, but is independent of transcription. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591820", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 594, "text": " In esc1Delta cells, Ulp1 and nuclear basket components Nup60 and Mlp1 no longer distribute broadly around the nuclear periphery, but co-localize in a small number of dense-staining perinuclear foci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17724121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11598013", "endSection": "title" }, { "offsetInBeginSection": 541, "offsetInEndSection": 712, "text": "NPCs assembled in the absence of Nup153 lacked several nuclear basket components, were unevenly distributed in the NE and, unlike wild-type NPCs, were mobile within the NE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11598013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Incorporation of the nuclear pore basket protein nup153 into nuclear pore structures is dependent upon lamina assembly: evidence from cell-free extracts of Xenopus eggs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10921874", "endSection": "title" }, { "offsetInBeginSection": 239, "offsetInEndSection": 419, "text": "Using light and EM immunolocalization, we determined that mammalian Tpr is concentrated within the nuclear basket of the pore complex in a distribution similar to Nup153 and Nup98.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11839768", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 636, "text": "Immunofluorescence and immunoelectron microscopy localize vertebrate Nup93 at the nuclear basket and at or near the nuclear entry to the gated channel of the pore.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9348540", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1129, "text": "Strikingly, Nup133 and Nup107 of the Nup107/160 subcomplex and Nup153 and Nup50 of the nuclear pore basket recruited a near full complement of nucleoporins to the LacO array.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25602437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Nup153 is a large (153 kD) O-linked glyco-protein which is a component of the basket structure located on the nucleoplasmic face of nuclear pore complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8794857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Nup153 is a molecular constituent of the nuclear basket of the nuclear pore complex (NPC) that plays a critical role in nuclear export of RNAs and proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10806081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The nucleoporins Nup60p, Nup2p, and Nup1p form part of the nuclear basket structure of the Saccharomyces cerevisiae nuclear pore complex (NPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11535617", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 606, "text": "By postembedding immunoelectron microscopy, we have mapped the positions of several human NPC proteins relative to the NPC core and its associated basket, including Nup93, Nup96, Nup98, Nup107, Nup153, Nup205, and the coiled coil-dominated 267-kDa protein Tpr.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15229283", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 594, "text": "In esc1Delta cells, Ulp1 and nuclear basket components Nup60 and Mlp1 no longer distribute broadly around the nuclear periphery, but co-localize in a small number of dense-staining perinuclear foci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17724121", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 646, "text": "Targeting information for Nup153 resides in the NH2-terminal domain since this region of the molecule can direct an ordinarily cytoplasmic protein, pyruvate kinase, to the nuclear face of the nuclear pore complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8794857", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 855, "text": "We show that the assembly and integrity of the nuclear basket is not affected by Nup153 depletion, whereas its integrity is perturbed in cells expressing high concentrations of the zinc-finger domain of Nup153.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25485891", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 432, "text": "When full-length human Nup153 is expressed in BHK cells, it accumulates appropriately at the nucleoplasmic face of the nuclear envelope.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8794857", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 439, "text": "One such protein, the nucleoporin Nup153, is localized to the nuclear basket of the pore complex and has been shown to be a central component of the nuclear transport machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11567018", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 517, "text": "Here, one SLAP is identified as the nuclear pore complex protein Nup153, one member of the F/GXFG motif-containing nucleoporins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10921874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.Nup133 belongs to the Y-complex, a key component of the nuclear pore complex (NPC) scaffold. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29791854", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins.The nuclear pore complex (NPC) is a large proteinaceous structure through which bidirectional transport of macromolecules across the nuclear envelope (NE) takes place. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11598013", "endSection": "title" }, { "offsetInBeginSection": 607, "offsetInEndSection": 863, "text": "To further assess their contributions to NPC and basket architecture, the genes encoding Nup93, Nup96, Nup107, and Nup205 were posttranscriptionally silenced by RNA interference (RNAi) in HeLa cells, complementing recent RNAi experiments on Nup153 and Tpr.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15229283", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1388, "text": "Immunogold-labeling for Nup98 also results in preferential labeling of NPC core regions, whereas Nup153 is shown to bind via its amino-terminal domain to the nuclear coaxial ring linking the NPC core structures and Tpr.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15229283", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1259, "text": "Ulp1, whose maintenance at nuclear pores depends on the Nup84 complex, impacts on THO-dependent gene expression, whereas the nuclear basket-associated Mlp1/Pml39 proteins prevent pre-mRNA export at a later stage, contributing to mRNA quality control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25845599", "endSection": "abstract" } ] }, { "body": "Does lucatumumab bind to CD140?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22475052" ], "ideal_answer": [ "No, lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC)." ], "exact_answer": "no", "type": "yesno", "id": "5c654c14e842deac67000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475052", "endSection": "title" }, { "offsetInBeginSection": 731, "offsetInEndSection": 889, "text": "Saturation of CD40 receptor on CLL cells was uniform at all doses post-treatment but also persisted at trough time points in the 3.0 mg/kg or greater cohorts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475052", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of arimoclomol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27009270", "http://www.ncbi.nlm.nih.gov/pubmed/15034571", "http://www.ncbi.nlm.nih.gov/pubmed/29090408", "http://www.ncbi.nlm.nih.gov/pubmed/22591194", "http://www.ncbi.nlm.nih.gov/pubmed/29367439", "http://www.ncbi.nlm.nih.gov/pubmed/20582873", "http://www.ncbi.nlm.nih.gov/pubmed/27605553", "http://www.ncbi.nlm.nih.gov/pubmed/30497978", "http://www.ncbi.nlm.nih.gov/pubmed/21445803", "http://www.ncbi.nlm.nih.gov/pubmed/19183864", "http://www.ncbi.nlm.nih.gov/pubmed/27273088", "http://www.ncbi.nlm.nih.gov/pubmed/24853414", "http://www.ncbi.nlm.nih.gov/pubmed/18551622", "http://www.ncbi.nlm.nih.gov/pubmed/23978556", "http://www.ncbi.nlm.nih.gov/pubmed/29159344", "http://www.ncbi.nlm.nih.gov/pubmed/18673445", "http://www.ncbi.nlm.nih.gov/pubmed/19938902", "http://www.ncbi.nlm.nih.gov/pubmed/23393146" ], "ideal_answer": [ "Arimoclomol is a heat shock protein co-inducer that promotes nascent protein folding. It enhances the ability of differentiated neurons to survive heat shock." ], "type": "summary", "id": "5c6636c57c78d69471000011", "snippets": [ { "offsetInBeginSection": 540, "offsetInEndSection": 683, "text": "Low dose co-application of celastrol and arimoclomol, which induces Hsps, enhanced the ability of differentiated neurons to survive heat shock.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29090408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "OBJECTIVE: To examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29367439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30497978", "endSection": "title" }, { "offsetInBeginSection": 459, "offsetInEndSection": 621, "text": "The investigational drug arimoclomol, which is in phase II/III clinical trials, is a well-characterized HSP amplifier and has been extensively clinically tested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30497978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Regioselective and enantiospecific synthesis of the HSP co-inducer arimoclomol from chiral glycidyl derivatives.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29159344", "endSection": "title" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1187, "text": "Oral administration of arimoclomol, a small-molecule coinducer of HSPs that is currently in clinical trials for Niemann-Pick disease type C (NPC), recapitulated the effects of recombinant human HSP70, suggesting that heat shock protein-based therapies merit clinical evaluation for treating LSDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27605553", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 486, "text": "Using rat myoblast cultures, we found that up-regulation of the heat shock response with arimoclomol reduced key pathological markers of sIBM in vitro. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009270", "endSection": "abstract" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1484, "text": "The mechanism of action of arimoclomol involves potentiation of the heat shock response, and treatment with arimoclomol increased Hsp70 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18673445", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 600, "text": "We have previously shown that treatment with a co-inducer of the heat shock response called arimoclomol is effective in the SOD(G93A) mouse model of ALS, delaying disease progression and extending the lifespan of SOD(G93A) mice (Kieran et al.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18673445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23978556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18551622", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1307, "text": "Arimoclomol is a co-activator that prolongs the binding of activated HSF1 to heat shock elements (HSEs) in the promoter regions of inducible Hsp genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27273088", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 619, "text": "The investigational drug arimoclomol, which is in phase II/III clinical trials, is a well-characterized HSP amplifier and has been extensively clinically tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30497978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Arimoclomol, an amplifier of heat shock protein expression involved in cellular stress response, has emerged as a potential therapeutic candidate in amyotrophic lateral sclerosis (ALS) in recent years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19938902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "OBJECTIVE To examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29367439", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1261, "text": "We have previously shown that treatment with arimoclomol, a co-inducer of the heat shock stress response, delays disease progression in the mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis, a fatal motor neuron disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393146", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1613, "text": "The mechanism of action of arimoclomol involves potentiation of the heat shock response, and treatment with arimoclomol increased Hsp70 expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18673445", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 369, "text": "The objectives of the present study were to assess the safety, tolerability, and pharmacokinetics of arimoclomol in ALS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18551622", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 804, "text": "In this review we summarize the evidence for the neuroprotective effects of enhanced heat shock protein expression by Arimoclomol and other inducers of the Heat Shock Response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23978556", "endSection": "abstract" } ] }, { "body": "What are the effects of STEF depletion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21460187", "http://www.ncbi.nlm.nih.gov/pubmed/29844364", "http://www.ncbi.nlm.nih.gov/pubmed/29072354" ], "ideal_answer": [ "The mechanisms regulating the actin cap are currently poorly understood. STEF/TIAM2, a Rac1 selective guanine nucleotide exchange factor, localises at the nuclear envelope, co-localising with the key perinuclear proteins Nesprin-2G and Non-muscle myosin IIB (NMMIIB), where it regulates perinuclear Rac1 activity. STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap." ], "exact_answer": [ [ "Reduction of apical perinuclear actin cables" ], [ "Decrease of nuclear stiffness" ], [ "Reduction of expression of TAZ-regulated genes" ] ], "type": "list", "id": "5c641179e842deac67000012", "snippets": [ { "offsetInBeginSection": 150, "offsetInEndSection": 1130, "text": "The mechanisms regulating the actin cap are currently poorly understood. Here, we demonstrate that STEF/TIAM2, a Rac1 selective guanine nucleotide exchange factor, localises at the nuclear envelope, co-localising with the key perinuclear proteins Nesprin-2G and Non-muscle myosin IIB (NMMIIB), where it regulates perinuclear Rac1 activity. We show that STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), increases nuclear height and impairs nuclear re-orientation. STEF down-regulation also reduces perinuclear pMLC and decreases myosin-generated tension at the nuclear envelope, suggesting that STEF-mediated Rac1 activity regulates NMMIIB activity to promote stabilisation of the perinuclear actin cap. Finally, STEF depletion decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29844364", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 690, "text": "We show that STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), increases nuclear height and impairs nuclear re-orientation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29844364", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1130, "text": "Finally, STEF depletion decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29844364", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 961, "text": "STEF depletion drastically reduced dbcAMP-induced neurite outgrowth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21460187", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1219, "text": "STEF depletion and Rac1-N17 expression reduced cAMP-induced TC10 inactivation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29072354", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1134, "text": "Finally, STEF depletion decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29844364", "endSection": "abstract" } ] }, { "body": "Please list symptoms of measles.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26613224", "http://www.ncbi.nlm.nih.gov/pubmed/29310585", "http://www.ncbi.nlm.nih.gov/pubmed/27168928", "http://www.ncbi.nlm.nih.gov/pubmed/15230469" ], "ideal_answer": [ "The leading symptoms of the disease are high fever that presents after an incubation period of 9-10 days and the red rash that begins several days after the fever starts. Beyond specific generalized symptoms, measles may have ocular symptoms. The most commonly occuring satellite symptoms are conjunctivitis, coryza and cough." ], "exact_answer": [ [ "red rash on skin" ], [ "high fever" ], [ "conjunctivitis" ], [ "coryza" ], [ "cough" ] ], "type": "list", "id": "5c53131e7e3cb0e231000012", "snippets": [ { "offsetInBeginSection": 375, "offsetInEndSection": 484, "text": "ever and generalized maculopapular rash, plus \u22651 of the following symptoms: Coryza, conjunctivitis, or cough.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Measles is a highly contagious viral infection associated with clinical symptoms such as fever, cough, conjunctivitis, coryza, eruption and increased serum immunoglobulin M (IgM) antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26613224", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 252, "text": "This patient had typical clinical measles infection symptoms: fever, rash, cough and coryza.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15230469", "endSection": "abstract" } ] }, { "body": "Does simvastatin improve outcomes of aneurysmal subarachnoid hemorrhage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28661267", "http://www.ncbi.nlm.nih.gov/pubmed/27160932", "http://www.ncbi.nlm.nih.gov/pubmed/28169856", "http://www.ncbi.nlm.nih.gov/pubmed/26587185", "http://www.ncbi.nlm.nih.gov/pubmed/28966073", "http://www.ncbi.nlm.nih.gov/pubmed/25516195", "http://www.ncbi.nlm.nih.gov/pubmed/26285662" ], "ideal_answer": [ "No. Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal subarachnoid hemorrhage. Patients with aneurysmal subarachnoid hemorrhage should not be treated routinely with simvastatin during the acute stage." ], "exact_answer": "no", "type": "yesno", "id": "5c73ad0b7c78d69471000093", "snippets": [ { "offsetInBeginSection": 897, "offsetInEndSection": 1078, "text": "Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28169856", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1381, "text": "Conclusions Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal SAH. We conclude that patients with SAH should not be treated routinely with simvastatin during the acute stage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28661267", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 807, "text": "We found no statistically significant effects on vasospasm detected by transcranial cerebral Doppler (relative risk [RR], 0.91; 95% confidence interval [CI], 0.55-1.49), delayed cerebral ischemia (DCI) (RR, 0.85; 95% CI, 0.63-1.14), or all-cause mortality (RR, 1.02; 95% CI, 0.67-1.54).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28661267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND: Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966073", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1689, "text": "CONCLUSIONS: Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS\u22642, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966073", "endSection": "abstract" }, { "offsetInBeginSection": 1744, "offsetInEndSection": 1838, "text": "Current evidence does not support prophylactic use of clazosentan, magnesium, or simvastatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27160932", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 247, "text": "Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26285662", "endSection": "abstract" }, { "offsetInBeginSection": 1571, "offsetInEndSection": 1720, "text": "CONCLUSIONS: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26285662", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1526, "text": "CONCLUSION: This study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26587185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26587185", "endSection": "title" }, { "offsetInBeginSection": 1577, "offsetInEndSection": 1725, "text": "CONCLUSIONS\nThe current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26285662", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1592, "text": "CONCLUSIONS\nHigh-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516195", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1079, "text": "Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28169856", "endSection": "abstract" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1694, "text": "CONCLUSIONS\nCompared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS\u22642, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966073", "endSection": "abstract" }, { "offsetInBeginSection": 1577, "offsetInEndSection": 1725, "text": "CONCLUSIONS The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26285662", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1592, "text": "CONCLUSIONS High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516195", "endSection": "abstract" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1694, "text": "CONCLUSIONS Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS\u22642, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966073", "endSection": "abstract" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1764, "text": "There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups.
CONCLUSIONS: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26285662", "endSection": "abstract" } ] }, { "body": "Which databases can exchange data using Matchmaker Exchange's API?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29044468" ], "ideal_answer": [ "Matchmaker Exchange (MME) was created to establish a federated network connecting databases of genomic and phenotypic data using a common application programming interface (API). To date, seven databases can exchange data using the API: GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching." ], "exact_answer": [ [ "GeneMatcher" ], [ "PhenomeCentral" ], [ "DECIPHER" ], [ "MyGene2" ], [ "matchbox" ], [ "Australian Genomics Health Alliance Patient Archive" ], [ "Monarch Initiative" ] ], "type": "list", "id": "5c641c60e842deac67000013", "snippets": [ { "offsetInBeginSection": 578, "offsetInEndSection": 1180, "text": "To facilitate such communication and improve the search for patients or model organisms with similar phenotypes and variants in specific candidate genes, we have developed the Matchmaker Exchange (MME). MME was created to establish a federated network connecting databases of genomic and phenotypic data using a common application programming interface (API). To date, seven databases can exchange data using the API (GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29044468", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1180, "text": "To date, seven databases can exchange data using the API (GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29044468", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1200, "text": "To date, seven databases can exchange data using the API (GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29044468", "endSection": "abstract" } ] }, { "body": "Is pazopanib an effective treatment of glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20200024", "http://www.ncbi.nlm.nih.gov/pubmed/23363814" ], "ideal_answer": [ "No. Pazopanib does not improve survival of glioblastoma patients." ], "exact_answer": "no", "type": "yesno", "id": "5c72aaed7c78d6947100006f", "snippets": [ { "offsetInBeginSection": 933, "offsetInEndSection": 1141, "text": "RESULTS: The six-month progression-free survival (PFS) rates in phase II (n = 41) were 0% and 15% in the PTEN/EGFRvIII-positive and PTEN/EGFRvIII-negative cohorts, respectively, leading to early termination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23363814", "endSection": "abstract" }, { "offsetInBeginSection": 1629, "offsetInEndSection": 1780, "text": "Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20200024", "endSection": "abstract" } ] }, { "body": "What is the purpose of the Ottawa Ankle Rule?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30183240", "http://www.ncbi.nlm.nih.gov/pubmed/26262468", "http://www.ncbi.nlm.nih.gov/pubmed/11782648", "http://www.ncbi.nlm.nih.gov/pubmed/28363615", "http://www.ncbi.nlm.nih.gov/pubmed/28965519", "http://www.ncbi.nlm.nih.gov/pubmed/29891469", "http://www.ncbi.nlm.nih.gov/pubmed/24971221", "http://www.ncbi.nlm.nih.gov/pubmed/25933807", "http://www.ncbi.nlm.nih.gov/pubmed/28764972" ], "ideal_answer": [ "Ottawa Ankle Rules is a clinical decision tool used to minimize unnecessary radiographs in ankle and foot injuries. It shows the areas of tenderness to be evaluated in ankle trauma patients to determine the need for imaging." ], "type": "summary", "id": "5c73ad0e7c78d69471000095", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "OBJECTIVE: The Ottawa Ankle Rules (OAR) are a clinical decision tool used to minimize unnecessary radiographs in ankle and foot injuries. The OAR are a reliable tool to exclude fractures in children over 5 years of age when applied by physicians. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28965519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "BACKGROUND: The Ottawa Ankle Rules, Ottawa Knee Rule, and Canadian C-Spine Rule-together known as The Ottawa Rules-are a set of internationally validated clinical decision rules developed to decrease unnecessary diagnostic imaging in the emergency department. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The Ottawa Ankle Rule shows the areas of tenderness to be evaluated in ankle trauma patients to determine the need for imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30183240", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 644, "text": "OBJECTIVE: It is important to further investigate the LRAR and compare them with the already validated Ottawa Ankle Rules (OAR) to potentially curb healthcare costs and decrease unnecessary radiation exposure without compromising diagnostic accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28363615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "BACKGROUND: Ankle decision rules are developed to expedite patient care and reduce the number of radiographs of the ankle and foot. Currently, only three systematic reviews have been conducted on the accuracy of the Ottawa Ankle and Foot Rules (OAFR) in adults and children. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28764972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "UNLABELLED: The original and modified Ottawa Ankle Rules (OARs) were developed as clinical decision rules for use in emergency departments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26262468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "PURPOSE: The Ottawa ankle rules (OAR) brought about a reduction of radiographs on the Emergency Department (ED). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25933807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Ottawa ankle rules and subjective surgeon perception to evaluate radiograph necessity following foot and ankle sprain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971221", "endSection": "title" }, { "offsetInBeginSection": 1566, "offsetInEndSection": 1692, "text": "CONCLUSION: The Ottawa ankle rules showed high reliability for deciding when to take radiographs in foot and/or ankle sprains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "PURPOSE\nThe Ottawa ankle rule (OAR) is a clinical decision rule used in emergency departments to identify which patients with acute ankle/midfoot injury require radiography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11782648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "BACKGROUND\nThe Ottawa Ankle Rules, Ottawa Knee Rule, and Canadian C-Spine Rule-together known as The Ottawa Rules-are a set of internationally validated clinical decision rules developed to decrease unnecessary diagnostic imaging in the emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891469", "endSection": "abstract" }, { "offsetInBeginSection": 1574, "offsetInEndSection": 1699, "text": "CONCLUSION The Ottawa ankle rules showed high reliability for deciding when to take radiographs in foot and/or ankle sprains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "PURPOSE The Ottawa ankle rule (OAR) is a clinical decision rule used in emergency departments to identify which patients with acute ankle/midfoot injury require radiography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11782648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Calculated Decisions: Ottawa Ankle RuleThe Ottawa Ankle Rule shows the areas of tenderness to be evaluated in ankle trauma patients to determine the need for imaging.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30183240", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Accuracy of the Ottawa Ankle Rules applied by non-physician providers in a pediatric emergency department.The Ottawa Ankle Rules (OAR) are a clinical decision tool used to minimize unnecessary radiographs in ankle and foot injuries. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28965519", "endSection": "title" } ] }, { "body": "What is CIBERSORT used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29796177", "http://www.ncbi.nlm.nih.gov/pubmed/30374348", "http://www.ncbi.nlm.nih.gov/pubmed/30117315", "http://www.ncbi.nlm.nih.gov/pubmed/29770915", "http://www.ncbi.nlm.nih.gov/pubmed/30479695", "http://www.ncbi.nlm.nih.gov/pubmed/26193342", "http://www.ncbi.nlm.nih.gov/pubmed/28405516", "http://www.ncbi.nlm.nih.gov/pubmed/29670256", "http://www.ncbi.nlm.nih.gov/pubmed/27737921", "http://www.ncbi.nlm.nih.gov/pubmed/27233495", "http://www.ncbi.nlm.nih.gov/pubmed/28193155", "http://www.ncbi.nlm.nih.gov/pubmed/25822800", "http://www.ncbi.nlm.nih.gov/pubmed/28826097", "http://www.ncbi.nlm.nih.gov/pubmed/27959923", "http://www.ncbi.nlm.nih.gov/pubmed/30261315", "http://www.ncbi.nlm.nih.gov/pubmed/29344893" ], "ideal_answer": [ "CIBERSORT is a versatile computational method for characterizing cell composition of complex tissues from their gene expression profiles.", "We recently described CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs)." ], "type": "summary", "id": "5c6ffde47c78d69471000059", "snippets": [ { "offsetInBeginSection": 522, "offsetInEndSection": 669, "text": "We recently described CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25822800", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 832, "text": "By applying CIBERSORT, a computational approach for inferring leukocyte representation in bulk tumor transcriptomes, we identified complex associations between 22 distinct leukocyte subsets and cancer survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26193342", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 776, "text": "We applied an established computational approach (CIBERSORT) to bulk gene expression profiles of almost 11,000 tumours to infer the proportions of 22 subsets of immune cells. We investigated associations between each cell type and survival and response to chemotherapy, modelling cellular proportions as quartiles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27959923", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1288, "text": "Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27233495", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1017, "text": "In this chapter, we provide a primer on the CIBERSORT method and illustrate its use for characterizing TILs in tumor samples profiled by microarray or RNA-Seq.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344893", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 668, "text": "We recently described CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344893", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 857, "text": "Combining support vector regression with prior knowledge of expression profiles from purified leukocyte subsets, CIBERSORT can accurately estimate the immune composition of a tumor biopsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344893", "endSection": "abstract" }, { "offsetInBeginSection": 2068, "offsetInEndSection": 2291, "text": "The main limitations of this study are the use of diverse platforms for measuring gene expression, including some not previously used with CIBERSORT, and the combined analysis of different forms of follow-up across studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27959923", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 434, "text": "In this study, based on a deconvolution algorithm (known as CIBERSORT) and clinical annotated expression profiles, we comprehensively analyzed the tumor-infiltrating immune cells present in CRC for the first time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30117315", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 534, "text": "In this study, based on a metagene approach (known as CIBERSORT) and an online databse, The Cancer Immunome Atlas (https://tcia.at/), we comprehensively analyzed the tumor-infiltrating immune cells present in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28826097", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1019, "text": "Using this framework we compare a widely used state-of-the-art reference-based algorithm (called constrained projection) to two non-constrained approaches including CIBERSORT and a method based on robust partial correlations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28193155", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 620, "text": "CYT was defined by GZMA and PRF1 expression, and CIBERSORT was used to evaluate intratumoral immune cell composition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29770915", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 816, "text": "CIBERSORT was used to estimate the fraction of 22 immune cell types to study their relations with pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27737921", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 831, "text": "By applying CIBERSORT, a computational approach for inferring leukocyte representation in bulk tumor transcriptomes, we identified complex associations between 22 distinct leukocyte subsets and cancer survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26193342", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 266, "text": "The recently developed CIBERSORT method allows immune cell profiling by deconvolution of gene expression microarray data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670256", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1493, "text": "Our data demonstrate that deconvolution of gene expression data by CIBERSORT provides valuable information about immune cell composition of HCC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670256", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 883, "text": "CIBERSORT was used to resolve 22 immune cell types from the tumor transcriptomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30374348", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 332, "text": "We used Cibersort to deconvolute immune cell components based on PBMCs or whole blood IPF genomics datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261315", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 522, "text": "Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize \u03b3\u03b4 T lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28405516", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 514, "text": "CIBERSORT should enable large-scale analysis of RNA mixtures for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu/).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25822800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25822800", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 895, "text": "Additionally, CIBERSORT in silico deconvolution was used to determine fractions of immune cell sub-populations within the gene expression datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479695", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 627, "text": "We analyzed IL-34 mRNA expression in breast cancer cell lines and breast cancer patients and applied established computational approaches (CIBERSORT, ESTIMATE, TIMER, TCIA), to analyze gene expression data from The Cancer Genome Atlas (TCGA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29796177", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 371, "text": "When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content and closely related cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25822800", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1021, "text": "In this chapter, we provide a primer on the CIBERSORT method and illustrate its use for characterizing TILs in tumor samples profiled by microarray or RNA-Seq.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344893", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 415, "text": "By applying CIBERSORT, we assessed the relative proportions of immune cells in 41 healthy human livers, 305 HCC samples and 82 HCC adjacent tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670256", "endSection": "abstract" } ] }, { "body": "Are de novo mutations in regulatory elements responsible for neurodevelopmental disorders?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29562236" ], "ideal_answer": [ "Yes. De novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. It is estimated that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism." ], "exact_answer": "yes", "type": "yesno", "id": "5c643485e842deac67000015", "snippets": [ { "offsetInBeginSection": 137, "offsetInEndSection": 1008, "text": "The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562236", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 1008, "text": "We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562236", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 607, "text": "Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562236", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 1081, "text": "We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562236", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 680, "text": "Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "De novo mutations in regulatory elements in neurodevelopmental disorders.We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562236", "endSection": "title" } ] }, { "body": "Which molecule is targeted by Olaratumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27291997", "http://www.ncbi.nlm.nih.gov/pubmed/28778132", "http://www.ncbi.nlm.nih.gov/pubmed/29191969", "http://www.ncbi.nlm.nih.gov/pubmed/29497315", "http://www.ncbi.nlm.nih.gov/pubmed/29413687", "http://www.ncbi.nlm.nih.gov/pubmed/24816152", "http://www.ncbi.nlm.nih.gov/pubmed/28620891", "http://www.ncbi.nlm.nih.gov/pubmed/30353601", "http://www.ncbi.nlm.nih.gov/pubmed/28917265", "http://www.ncbi.nlm.nih.gov/pubmed/30513001", "http://www.ncbi.nlm.nih.gov/pubmed/29478115", "http://www.ncbi.nlm.nih.gov/pubmed/28838379", "http://www.ncbi.nlm.nih.gov/pubmed/27995580", "http://www.ncbi.nlm.nih.gov/pubmed/28745071", "http://www.ncbi.nlm.nih.gov/pubmed/28447475", "http://www.ncbi.nlm.nih.gov/pubmed/28691538", "http://www.ncbi.nlm.nih.gov/pubmed/30406840", "http://www.ncbi.nlm.nih.gov/pubmed/29263653", "http://www.ncbi.nlm.nih.gov/pubmed/24452395", "http://www.ncbi.nlm.nih.gov/pubmed/28187274", "http://www.ncbi.nlm.nih.gov/pubmed/28734947" ], "ideal_answer": [ "Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-\u03b1 (PDGFR\u03b1). It is used for treatment of soft tissue sarcoma." ], "exact_answer": [ "platelet-derived growth factor receptor-\u03b1" ], "type": "factoid", "id": "5c73ad367c78d69471000099", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Population Pharmacokinetic Modeling of Olaratumab, an Anti-PDGFR\u03b1 Human Monoclonal Antibody, in Patients with Advanced and/or Metastatic Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620891", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND AND OBJECTIVES: Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-\u03b1 (PDGFR\u03b1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620891", "endSection": "abstract" }, { "offsetInBeginSection": 1350, "offsetInEndSection": 1558, "text": "Conclusions: Overall, these data indicate that olaratumab, alone and in combination with standard of care, blocks the growth of some preclinical PDGFR\u03b1-expressing pediatric bone and soft tissue tumor models. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29191969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Recent randomised phase II trial data have indicated that the addition of olaratumab, a novel monoclonal antibody against platelet-derived growth factor receptor alpha (PDGFR\u03b1), to doxorubicin confers an unprecedented improvement in overall survival to patients with anthracycline-na\u00efve advanced soft tissue sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413687", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 849, "text": "While preclinical data show that olaratumab specifically inhibits PDGFR\u03b1-mediated oncogenic signalling with attendant anti-tumour effects, a lack of correlation between pharmacodynamics markers of PDGFR\u03b1 inhibition and clinical benefit from olaratumab suggest other mechanisms beyond modulation of downstream PDGFR\u03b1 molecular pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Lartruvo\u00ae (olaratumab) is a fully human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that inhibits platelet-derived growth factor receptor alpha (PDGFR\u03b1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29497315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Olaratumab (Lartruvo\u2122) is a fully human IgG1 monoclonal antibody targeted against the human platelet-derived growth factor (PDGF) receptor \u03b1 (PDGFR\u03b1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27995580", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 448, "text": "Olaratumab acts by selectively binding PDGFR\u03b1, thereby blocking PDGF ligand binding and inhibiting PDGFR\u03b1 activation and downstream signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27995580", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 435, "text": "Olaratumab is a human antiplatelet-derived growth factor receptor \u03b1 monoclonal antibody that has antitumour activity in human sarcoma xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27291997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "PURPOSE\nOlaratumab is a recombinant human IgG1 monoclonal antibody against PGDFR\u03b1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30406840", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 234, "text": "Recently, inhibition of platelet-derived growth factor receptor (PDGFR)-\u03b1 by the monoclonal antibody olaratumab showed promising clinical activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28917265", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 241, "text": "Olaratumab (IMC-3G3) is a fully human anti-PDGFR\u03b1 monoclonal antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28838379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Olaratumab is a humanized IgG1 monoclonal antibody that blocks the platelet-derived growth factor receptor alpha (PDGFR\u03b1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28447475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Lartruvo\u00ae (olaratumab) is a fully human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that inhibits platelet-derived growth factor receptor alpha (PDGFR\u03b1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29497315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody that selectively binds the external domain of human platelet-derived growth factor receptor-\u03b1 with high affinity and blocks ligand binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816152", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 654, "text": "Olaratumab is a fully human IgG1-type anti-PDGFR-\u03b1 monoclonal antibody with a high affinity and a low 50% inhibitory concentration (IC50).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28691538", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 242, "text": "Olaratumab (IMC-3G3) is a fully human monoclonal antibody that selectively binds human PDGFR\u03b1 and blocks ligand binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24452395", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 563, "text": "Olaratumab is a fully human IgG1 monoclonal antibody that binds to platelet-derived growth factor receptor \u03b1 (PDGFR-\u03b1) preventing binding of its ligands and receptor activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29263653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "BACKGROUND AND OBJECTIVES Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-\u03b1 (PDGFR\u03b1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Olaratumab, a monoclonal antibody targeting human platelet-derived growth factor receptor \u03b1, plus doxorubicin significantly improved overall survival in patients with advanced soft-tissue sarcoma (STS) in a prior phase 1b/2 randomized trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30353601", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 482, "text": "Olaratumab (LY3012207/IMC-3G3) is a human mAb that exclusively binds to PDGFR\u03b1 and recently received accelerated FDA approval and conditional EMA approval for treatment of advanced adult sarcoma patients in combination with doxorubicin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29191969", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1254, "text": "The most important is the combination of the standard cytotoxic agent doxorubicin plus the platelet-derived growth factor receptor (PDGFR) inhibitor olaratumab, although definitive results from a phase III trial are expected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30513001", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 680, "text": "DATA SYNTHESIS Olaratumab is a human antiplatelet-derived growth factor receptor \u03b1 monoclonal antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28778132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Lartruvo (olaratumab) is a monoclonal antibody against the extracellular domain of PDGFRA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28187274", "endSection": "abstract" }, { "offsetInBeginSection": 1076, "offsetInEndSection": 1513, "text": "Using phospho-specific antibodies, we show that olaratumab attenuates PDGFR\u03b1 activation in response to PDGF-BB, and reduced phosphorylation of extracellular signal-regulated kinase 1 and 2, Elk-1, p38, Akt, focal adhesion kinase, mechanistic target of rapamycin, C10 regulator of kinase II, and C10 regulator of kinase-like, suggesting that PDGFR\u03b1 contributes to mitogenesis and actin reorganization through diverse downstream effectors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28734947", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 378, "text": "Olaratumab (IMC-3G3) is a fully human anti-PDGFR\u03b1 monoclonal antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28838379", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1002, "text": "Olaratumab is a human antiplatelet-derived growth factor receptor \u03b1 monoclonal antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28778132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Olaratumab: First Global Approval.Olaratumab (Lartruvo\u2122) is a fully human IgG1 monoclonal antibody targeted against the human platelet-derived growth factor (PDGF) receptor \u03b1 (PDGFR\u03b1). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27995580", "endSection": "title" }, { "offsetInBeginSection": 479, "offsetInEndSection": 624, "text": "Olaratumab is a human antiplatelet-derived growth factor receptor \u03b1 monoclonal antibody that has antitumour activity in human sarcoma xenografts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27291997", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 482, "text": "Olaratumab acts by selectively binding PDGFR\u03b1, thereby blocking PDGF ligand binding and inhibiting PDGFR\u03b1 activation and downstream signalling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27995580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Phase I study of olaratumab in Japanese patients with advanced solid tumors.Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody that selectively binds the external domain of human platelet-derived growth factor receptor-\u03b1 with high affinity and blocks ligand binding. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24816152", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Population Pharmacokinetic Modeling of Olaratumab, an Anti-PDGFR\u03b1 Human Monoclonal Antibody, in Patients with Advanced and/or Metastatic Cancer.Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-\u03b1 (PDGFR\u03b1). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620891", "endSection": "title" }, { "offsetInBeginSection": 291, "offsetInEndSection": 503, "text": "A Phase Ib/randomized Phase II trial of doxorubicin with or without the monoclonal antibody to PDGFR-\u03b1, olaratumab, demonstrated a significant difference in median overall survival in favor of the olaratumab arm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28745071", "endSection": "abstract" } ] }, { "body": "What is PANDAS disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29119300", "http://www.ncbi.nlm.nih.gov/pubmed/16970875", "http://www.ncbi.nlm.nih.gov/pubmed/28498087", "http://www.ncbi.nlm.nih.gov/pubmed/29722936", "http://www.ncbi.nlm.nih.gov/pubmed/18817720", "http://www.ncbi.nlm.nih.gov/pubmed/20864184", "http://www.ncbi.nlm.nih.gov/pubmed/25151976", "http://www.ncbi.nlm.nih.gov/pubmed/19913659", "http://www.ncbi.nlm.nih.gov/pubmed/24019622", "http://www.ncbi.nlm.nih.gov/pubmed/30325890", "http://www.ncbi.nlm.nih.gov/pubmed/29112476" ], "ideal_answer": [ "PANDAS stands for (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) and has been suggested to be a result of a disordered immune response following an infection causing neuropsychiatric symptoms." ], "type": "summary", "id": "5c6db9917c78d69471000043", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29119300", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 191, "text": "Antibiotics have been used extensively by clinicians to treat patients with PANDAS or PANS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29722936", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 112, "text": "The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30325890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "OBJECTIVES\nPediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24019622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25151976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "PANDAS Syndrome (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) is a rare disease described in 1998.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18817720", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 520, "text": "PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive-compulsive disorder consistently exacerbate in temporal correlation to a group A beta-hemolytic streptococcal infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16970875", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 499, "text": "Of recent interest, a subtype of obsessive-compulsive disorder (OCD) and tic disorders known collectively as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is believed to be secondary to central nervous system (CNS) autoimmunity that occurs in relation to group A streptococcal infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20864184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "OBJECTIVES Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24019622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Diagnosis and treatment of the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) variant of Gilles de la Tourette syndrome (GTS) and childhood-onset obsessive-compulsive disorder (OCD) are still controversial issues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19913659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "BACKGROUND Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are immune-mediated diseases characterized by obsessive-compulsive symptoms and/or tics triggered by group A Streptococcus infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "'Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections' (PANDAS) identified a unique subgroup of patients with abrupt onset of obsessive compulsive disorder (OCD) symptoms clinically related to Streptococcus infection and accompanied by neuropsychological and motor symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28498087", "endSection": "abstract" } ] }, { "body": "Are phagosomal proteins ubiquitinated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15703218", "http://www.ncbi.nlm.nih.gov/pubmed/29376029" ], "ideal_answer": [ "Yes,\nPhagosomal proteins are ubiquitylated, and ubiquitylation was found to be required for formation of acidic multivesicular structures." ], "exact_answer": "yes", "type": "yesno", "id": "5c7c0e2fd774d0424000000d", "snippets": [ { "offsetInBeginSection": 1134, "offsetInEndSection": 1267, "text": "Phagosomal proteins are ubiquitylated, and ubiquitylation was found to be required for formation of acidic multivesicular structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703218", "endSection": "abstract" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1317, "text": "membranes of the bacterial phagosome are enriched with ubiquitinated proteins in a way that requires its Dot/Icm type IV secretion system, suggesting the involvement of effectors in the manipulation of the host ubiquitination machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29376029", "endSection": "abstract" } ] }, { "body": "A herd immunity of what percentage of the population is required to prevent sporadic outbreaks?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24303998" ], "ideal_answer": [ "A herd immunity of 95% of the population is required to prevent sporadic outbreaks." ], "exact_answer": [ "95 %" ], "type": "factoid", "id": "5c7b1a5fd774d0424000000c", "snippets": [ { "offsetInBeginSection": 226, "offsetInEndSection": 318, "text": "herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24303998", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 317, "text": "However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24303998", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 431, "text": "However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24303998", "endSection": "abstract" } ] }, { "body": "Does tremelimumab improve survival of mesothelioma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28231719", "http://www.ncbi.nlm.nih.gov/pubmed/28729154", "http://www.ncbi.nlm.nih.gov/pubmed/29773326" ], "ideal_answer": [ "No. Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma." ], "exact_answer": "no", "type": "yesno", "id": "5c73ad327c78d69471000097", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "BACKGROUND: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29773326", "endSection": "abstract" }, { "offsetInBeginSection": 2599, "offsetInEndSection": 2768, "text": "INTERPRETATION: The combination of tremelimumab and durvalumab appeared active, with a good safety profile in patients with mesothelioma, warranting further exploration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29773326", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 751, "text": "Biological and clinical considerations rule out the use of tremelimumab as single agent for MM and, more generally, the use of immune checkpoint inhibitors for MM is still largely questionable and not supported by evidences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231719", "endSection": "abstract" }, { "offsetInBeginSection": 1936, "offsetInEndSection": 2352, "text": "At the data cutoff date (Jan 24, 2016), 307 (80%) of 382 patients had died in the tremelimumab group and 154 (81%) of 189 patients had died in the placebo group. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7\u00b77 months (95% CI 6\u00b78-8\u00b79) in the tremelimumab group and 7\u00b73 months (5\u00b79-8\u00b77) in the placebo group (hazard ratio 0\u00b792 [95% CI 0\u00b776-1\u00b712], p=0\u00b741). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28729154", "endSection": "abstract" }, { "offsetInBeginSection": 3790, "offsetInEndSection": 3947, "text": "INTERPRETATION: Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28729154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "BACKGROUND\nTremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29773326", "endSection": "abstract" }, { "offsetInBeginSection": 3796, "offsetInEndSection": 3952, "text": "INTERPRETATION\nTremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28729154", "endSection": "abstract" }, { "offsetInBeginSection": 2101, "offsetInEndSection": 2354, "text": "Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7\u00b77 months (95% CI 6\u00b78-8\u00b79) in the tremelimumab group and 7\u00b73 months (5\u00b79-8\u00b77) in the placebo group (hazard ratio 0\u00b792 [95% CI 0\u00b776-1\u00b712], p=0\u00b741).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28729154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "BACKGROUND Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29773326", "endSection": "abstract" }, { "offsetInBeginSection": 3796, "offsetInEndSection": 3952, "text": "INTERPRETATION Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28729154", "endSection": "abstract" }, { "offsetInBeginSection": 2383, "offsetInEndSection": 2636, "text": "Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7\u00b77 months (95% CI 6\u00b78-8\u00b79) in the tremelimumab group and 7\u00b73 months (5\u00b79-8\u00b77) in the placebo group (hazard ratio 0\u00b792 [95% CI 0\u00b776-1\u00b712], p=0\u00b741). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28729154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "BACKGROUND: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29773326", "endSection": "abstract" } ] }, { "body": "Can enasidenib be used for the treatment of acute myeloid leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29770715" ], "ideal_answer": [ "Yes, enasidenib has been approved for the treatment of adults with relapsed and refracctory acture myelogenous leukemia with an IDH2 mutation." ], "exact_answer": "yes", "type": "yesno", "id": "5c6587d77c78d69471000005", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 222, "text": "In August 2017, the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29770715", "endSection": "abstract" } ] }, { "body": "What membrane proteins constitute TAM family of receptor tyrosine kinases (RTKs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24184575", "http://www.ncbi.nlm.nih.gov/pubmed/27780404", "http://www.ncbi.nlm.nih.gov/pubmed/28734578", "http://www.ncbi.nlm.nih.gov/pubmed/28034848", "http://www.ncbi.nlm.nih.gov/pubmed/27895032", "http://www.ncbi.nlm.nih.gov/pubmed/18620092", "http://www.ncbi.nlm.nih.gov/pubmed/25568918", "http://www.ncbi.nlm.nih.gov/pubmed/28904208", "http://www.ncbi.nlm.nih.gov/pubmed/22749189", "http://www.ncbi.nlm.nih.gov/pubmed/18374195" ], "ideal_answer": [ "Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs).", "TAM-family RTKs AXL and Mer (MerTK)." ], "exact_answer": [ [ "Tyro3" ], [ "Axl" ], [ "Mer" ] ], "type": "list", "id": "5c5315727e3cb0e231000014", "snippets": [ { "offsetInBeginSection": 677, "offsetInEndSection": 714, "text": "TAM-family RTKs AXL and Mer (MerTK). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Deregulation of the TAM (TYRO3, AXL, and MERTK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28034848", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1015, "text": "TAM family members AXL or TYRO3 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28904208", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 748, "text": "receptors of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases (RTKs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28734578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Tyro-3, Axl, and Mer constitute the TAM family of receptor tyrosine kinases (RTKs) characterized by a conserved sequence within the kinase domain and adhesion molecule-like extracellular domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18620092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25568918", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 376, "text": "Gas6 was cloned and characterized in 1993 and found to be similar to the plasma anticoagulant protein S. Soon after it was recognized as a growth factor-like molecule, as it interacted with receptor tyrosine kinases (RTKs) of the TAM family; Tyro3, Axl, and MerTK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18374195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The TAM subfamily of Receptor Tyrosine Kinases (RTKs) contains three human proteins of therapeutical interest, Axl, Mer, and Tyro3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749189", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 383, "text": "Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27780404", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 830, "text": "Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27780404", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 790, "text": "A series of recent studies now consolidates the view that phosphatidylserine (PtdSer), a common phospholipid constituent of membrane bilayers, is similarly repurposed for use as a signal between cells and that the ligands and receptors of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases (RTKs) are prominent transducers of this signal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28734578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer.The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial malignancies. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25568918", "endSection": "title" }, { "offsetInBeginSection": 566, "offsetInEndSection": 724, "text": "The TAM family of RTKs, consisting of Tyro3, Axl, and MerTK, is prominently expressed during the development and function of the central nervous system (CNS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24184575", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 627, "text": "The TAM family of RTKs, consisting of Tyro3, Axl, and MerTK, is prominently expressed during the development and function of the central nervous system (CNS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24184575", "endSection": "abstract" } ] }, { "body": "What are the effects of the deletion of all three Pcdh clusters (tricluster deletion) in mice?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28450637" ], "ideal_answer": [ "Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly. The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdh\u03b1, Pcdh\u03b2, and Pcdh\u03b3). Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance.", "The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdh\u03b1, Pcdh\u03b2, and Pcdh\u03b3). Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance." ], "exact_answer": [ [ "Severe axonal arborization defect" ], [ "Loss of self-avoidance" ] ], "type": "list", "id": "5c645313e842deac67000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28450637", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 584, "text": "The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdh\u03b1, Pcdh\u03b2, and Pcdh\u03b3). Here, we show that all three gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons (OSNs) with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb. Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28450637", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 584, "text": "Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28450637", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 378, "text": "Here, we show that all three gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons (OSNs) with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28450637", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 696, "text": "Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28450637", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 483, "text": "Here, we show that all three gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons (OSNs) with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28450637", "endSection": "abstract" } ] }, { "body": "What is CPX351?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29378418" ], "ideal_answer": [ "CPX-351, a novel liposomal formulation which encapsulates cytarabine and daunorubicin in 5:1 molar ratio, has shown promising efficacy, leading to recent US FDA approval for front-line therapy for patients with therapy-related AML and AML with myelodysplasia-related changes based on a large multicenter Phase III clinical trial." ], "type": "summary", "id": "5c6548d4e842deac67000020", "snippets": [ { "offsetInBeginSection": 396, "offsetInEndSection": 725, "text": "CPX-351, a novel liposomal formulation which encapsulates cytarabine and daunorubicin in 5:1 molar ratio, has shown promising efficacy, leading to recent US FDA approval for front-line therapy for patients with therapy-related AML and AML with myelodysplasia-related changes based on a large multicenter Phase III clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29378418", "endSection": "abstract" } ] }, { "body": "Is collagen the most abundant human protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29146366", "http://www.ncbi.nlm.nih.gov/pubmed/29144022", "http://www.ncbi.nlm.nih.gov/pubmed/28929384" ], "ideal_answer": [ "Yes, collagen is the most abundant protein family in mammals." ], "exact_answer": "yes", "type": "yesno", "id": "5c783236d774d04240000001", "snippets": [ { "offsetInBeginSection": 154, "offsetInEndSection": 336, "text": "As the most abundant protein in the body, collagen is essential to maintain the normal structure and strength of connective tissue, such as bones, skin, cartilage, and blood vessels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Collagen is the most abundant protein family in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29146366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Collagen is a fibrillar protein that conforms the conjunctive and connective tissues in the human body, essentially skin, joints, and bones. This molecule is one of the most abundant in many of the living organisms due to its connective role in biological structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29144022", "endSection": "abstract" } ] }, { "body": "What micro-RNAs are useful in the diagnosis and prognosis of Heart Failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23242657", "http://www.ncbi.nlm.nih.gov/pubmed/28842125", "http://www.ncbi.nlm.nih.gov/pubmed/22011751", "http://www.ncbi.nlm.nih.gov/pubmed/22735911" ], "ideal_answer": [ "In particular, miR-214, miR-423-5p, appear to be promising for the diagnosis, prognosis and management of HF patients." ], "exact_answer": [ [ "miR-214" ], [ "miR-423-5p" ] ], "type": "list", "id": "5c6ffdd47c78d69471000058", "snippets": [ { "offsetInBeginSection": 919, "offsetInEndSection": 1157, "text": "n this review, we discuss the role of miR-214 in various cardiac disease conditions, including ischaemic heart diseases, cardiac hypertrophy, pulmonary arterial hypertension (PAH), angiogenesis following vascular injury and heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28842125", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 977, "text": "Likewise, serum levels of c-miRNAs such as miR-423-5p have been evaluated as potential biomarkers in the diagnosis and prognosis of heart failure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242657", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 708, "text": "Serum levels of circulating miRNAs such as miR-423-5p are being evaluated as potential biomarkers in the diagnosis and prognosis of heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22735911", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 978, "text": "Likewise, serum levels of c-miRNAs such as miR-423-5p have been evaluated as potential biomarkers in the diagnosis and prognosis of heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23242657", "endSection": "abstract" } ] }, { "body": "What is ivosidenib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29670690" ], "ideal_answer": [ "AG-120 (ivosidenib) ia an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity." ], "type": "summary", "id": "5c654aede842deac67000023", "snippets": [ { "offsetInBeginSection": 460, "offsetInEndSection": 869, "text": "Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "endSection": "abstract" } ] }, { "body": "List proteins interacting with Star-PAP", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21102410", "http://www.ncbi.nlm.nih.gov/pubmed/24768001", "http://www.ncbi.nlm.nih.gov/pubmed/26138484", "http://www.ncbi.nlm.nih.gov/pubmed/18288197" ], "ideal_answer": [ "Phosphorylation regulates the Star-PAP-PIPKI\u03b1 interaction and directs specificity toward mRNA targets.\nStar-PAP directly associated with cleavage and polyadenylation specificity factor (CPSF) 160 and 73 subunits and also the targeted pre-mRNA.\nwe show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability." ], "exact_answer": [ [ "PIPKI\u03b1" ], [ "CPSF 160" ], [ "CPSF 73" ], [ "Larp7" ] ], "type": "list", "id": "5c5f11c31a4c55d80b000015", "snippets": [ { "offsetInBeginSection": 1305, "offsetInEndSection": 1359, "text": "Star-PAP and PIPKIalpha function together in a complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18288197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Phosphorylation regulates the Star-PAP-PIPKI\u03b1 interaction and directs specificity toward mRNA targets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26138484", "endSection": "title" }, { "offsetInBeginSection": 740, "offsetInEndSection": 840, "text": ", we show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24768001", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 590, "text": "Star-PAP directly associated with cleavage and polyadenylation specificity factor (CPSF) 160 and 73 subunits and also the targeted pre-mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21102410", "endSection": "abstract" } ] }, { "body": "Describe symptoms of the Visual snow syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28723606", "http://www.ncbi.nlm.nih.gov/pubmed/29140814", "http://www.ncbi.nlm.nih.gov/pubmed/29934719", "http://www.ncbi.nlm.nih.gov/pubmed/30383334", "http://www.ncbi.nlm.nih.gov/pubmed/30095537", "http://www.ncbi.nlm.nih.gov/pubmed/27508888", "http://www.ncbi.nlm.nih.gov/pubmed/29193050" ], "ideal_answer": [ "Visual snow (VS) is a constant visual disturbance described as flickering dots occupying the entire visual field. Recently, it was characterized as the defining feature of a VS syndrome (VSS), which includes palinopsia, photophobia, photopsias, entoptic phenomena, nyctalopia, and tinnitus." ], "type": "summary", "id": "5c72f9847c78d69471000081", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "PURPOSE OF REVIEW: We provide an overview of the neurological condition known as visual snow syndrome. Patients affected by this chronic disorder suffer with a pan-field visual disturbance described as tiny flickering dots, which resemble the static noise of an untuned television.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29140814", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 365, "text": "BACKGROUND: Visual snow is a persistent visual disturbance characterized by rapid flickering dots throughout the visual field. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29193050", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 530, "text": "RECENT FINDINGS: Visual snow is a condition where patients see constant, innumerable flickering dots throughout the visual field, similar to \"TV static.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "BACKGROUND: Visual snow (VS) is a constant visual disturbance described as flickering dots occupying the entire visual field. Recently, it was characterized as the defining feature of a VS syndrome (VSS), which includes palinopsia, photophobia, photopsias, entoptic phenomena, nyctalopia, and tinnitus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Patients with visual snow syndrome (VS) suffer from a debilitating continuous visual disturbance of unknown mechanism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30383334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Background The symptom \"visual snow\" describes the continuous perception of tiny flickering dots within the whole visual field of both eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27508888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Visual snow is a symptom described as the continuous perception of tiny flickering dots in the entire field of vision, similar to static of an analog television.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28723606", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 548, "text": "We also discuss the theories on the pathophysiological mechanisms of visual snow, as well as the current approach to treatment.
RECENT FINDINGS: Visual snow is a condition where patients see constant, innumerable flickering dots throughout the visual field, similar to \"TV static.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "ABSTRACT: Visual snow is a symptom described as the continuous perception of tiny flickering dots in the entire field of vision, similar to static of an analog television.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28723606", "endSection": "abstract" } ] }, { "body": "What is the role of the Leucosporidium ice-binding protein", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23203635", "http://www.ncbi.nlm.nih.gov/pubmed/22303017", "http://www.ncbi.nlm.nih.gov/pubmed/24699650", "http://www.ncbi.nlm.nih.gov/pubmed/30296411" ], "ideal_answer": [ "Arctic yeast Leucosporidium sp. produces a glycosylated ice-binding protein (LeIBP) with a molecular mass of \u223c25 kDa, which can lower the freezing point below the melting point once it binds to ice. ce-binding proteins (IBPs) inhibit ice growth through direct interaction with ice crystals to permit the survival of polar organisms in extremely cold environments." ], "type": "summary", "id": "5c5f18501a4c55d80b000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Ice-binding proteins (IBPs) inhibit ice growth through direct interaction with ice crystals to permit the survival of polar organisms in extremely cold environments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24699650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Ice-binding proteins (IBPs) can bind to the ice crystal and inhibit its growth. Because this property of IBPs can increase the freeze-thaw survival of cells, IBPs have attracted the attention from industries for their potential use in biotechnological applications", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23203635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Arctic yeast Leucosporidium sp. produces a glycosylated ice-binding protein (LeIBP) with a molecular mass of \u223c25 kDa, which can lower the freezing point below the melting point once it binds to ice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22303017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Ice binding proteins (IBPs) have been attracting significant interest on account of their characteristic of inhibiting ice growth and recrystallization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30296411", "endSection": "abstract" } ] }, { "body": "Is the enzyme ERAP2 associated with the disease birdshot chorioretinopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24957906", "http://www.ncbi.nlm.nih.gov/pubmed/29769354" ], "ideal_answer": [ "Yes,\nBSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands." ], "exact_answer": "yes", "type": "yesno", "id": "5c76be617c78d694710000a5", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29769354", "endSection": "title" }, { "offsetInBeginSection": 124, "offsetInEndSection": 311, "text": "BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29769354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24957906", "endSection": "title" } ] }, { "body": "As of September 2018, what machine learning algorithm is used to for cardiac arrhythmia detection from a short single-lead ECG recorded by a wearable device?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30102239" ], "ideal_answer": [ "Support Vector machines( SVM) can be used for cardiac arrhythmia detection in from an ECG recorded by a wearable device.", "SVM approach for cardiac arrhythmias detection in short single-lead ECG recorded by a wearable device" ], "exact_answer": [ "SVM OR Support Vector Machine" ], "type": "factoid", "id": "5c5219f67e3cb0e231000006", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 113, "text": "SVM approach for cardiac arrhythmias detection in short single-lead ECG recorded by a wearable device", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30102239", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Multi-stage SVM approach for cardiac arrhythmias detection in short single-lead ECG recorded by a wearable device.Use of wearable ECG devices for arrhythmia screening is limited due to poor signal quality, small number of leads and short records, leading to incorrect recognition of pathological events. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30102239", "endSection": "title" } ] }, { "body": "Does Panitumumab prolong survival of biliary tract cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23819169", "http://www.ncbi.nlm.nih.gov/pubmed/29413685", "http://www.ncbi.nlm.nih.gov/pubmed/29893894", "http://www.ncbi.nlm.nih.gov/pubmed/26540314" ], "ideal_answer": [ "No. Panitumumab in combination with chemotherapy does not improve survival of biliary cancer patients." ], "exact_answer": "no", "type": "yesno", "id": "5c73ad377c78d6947100009a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26540314", "endSection": "title" }, { "offsetInBeginSection": 1769, "offsetInEndSection": 1918, "text": "CONCLUSIONS: Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413685", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1340, "text": "No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P\u2009=\u2009.42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P\u2009=\u2009.13). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26540314", "endSection": "abstract" }, { "offsetInBeginSection": 1775, "offsetInEndSection": 1922, "text": "CONCLUSIONS\nPanitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413685", "endSection": "abstract" }, { "offsetInBeginSection": 1775, "offsetInEndSection": 1922, "text": "CONCLUSIONS Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413685", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1242, "text": "Despite many clinical trials being conducted with molecular targeted agents including erlotinib, cetuximab, panitumumab, bevacizumab, sorafenib, cediranib, trametinib and vandetanib, no agent has shown to be effective for advanced biliary tract cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29893894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Adding panitumumab to standard protocols does not prolong survival but provokes additional adverse effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23819169", "endSection": "abstract" } ] }, { "body": "Which microRNA is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "http://www.ncbi.nlm.nih.gov/pubmed/22003227" ], "ideal_answer": [ "MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions." ], "exact_answer": [ "MIR137" ], "type": "factoid", "id": "5c630666e842deac6700000c", "snippets": [ { "offsetInBeginSection": 461, "offsetInEndSection": 552, "text": "MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 555, "text": "CONCLUSIONS\nThis study suggests that MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 424, "text": "CASE PRESENTATION\nWe describe a 10-year-old boy with syndromic obesity who carries a novel 1p21.3\u00a0deletion overlapping the critical region with the MIR137 gene only.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1841, "text": "CONCLUSIONS\nThis study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 555, "text": "CONCLUSIONS This study suggests that MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 424, "text": "CASE PRESENTATION We describe a 10-year-old boy with syndromic obesity who carries a novel 1p21.3\u00a0deletion overlapping the critical region with the MIR137 gene only.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 1641, "offsetInEndSection": 1841, "text": "CONCLUSIONS This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1078, "text": "Therefore, this study investigated the possible involvement of MIR137 in the 1p21.3-deletion phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": 1862, "offsetInEndSection": 2110, "text": "This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 662, "text": "We describe a 10-year-old boy with syndromic obesity who carries a novel 1p21.3\u00a0deletion overlapping the critical region with the MIR137 gene only. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 861, "text": "This study suggests that MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "MIR137 is the key gene mediator of the syndromic obesity phenotype of patients with 1p21.3 microdeletions.Deletions in the long arm of chromosome 1 have been described in patients with a phenotype consisting primarily of obesity, intellectual disability and autism-spectrum disorder. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "title" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1095, "text": "Therefore, this study investigated the possible involvement of MIR137 in the 1p21.3-deletion phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1867, "text": "The study also demonstrated significant enrichment of miR-137 at the synapses of cortical and hippocampal neurons, suggesting a role of miR-137 in regulating local synaptic protein synthesis machinery.
CONCLUSIONS: This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 105, "text": "MIR137 is the key gene mediator of the syndromic obesity phenotype of patients with 1p21.3 microdeletions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "title" }, { "offsetInBeginSection": 394, "offsetInEndSection": 510, "text": "This study suggests that MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 393, "text": "We describe a 10-year-old boy with syndromic obesity who carries a novel 1p21.3\u00a0deletion overlapping the critical region with the MIR137 gene only.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1794, "text": "This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "title" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1045, "text": "Therefore, this study investigated the possible involvement of MIR137 in the 1p21.3-deletion phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" } ] }, { "body": "What is the aim of the METABRIC project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26132585", "http://www.ncbi.nlm.nih.gov/pubmed/28620450", "http://www.ncbi.nlm.nih.gov/pubmed/26770261", "http://www.ncbi.nlm.nih.gov/pubmed/30097312", "http://www.ncbi.nlm.nih.gov/pubmed/22912679", "http://www.ncbi.nlm.nih.gov/pubmed/29532008", "http://www.ncbi.nlm.nih.gov/pubmed/30181556", "http://www.ncbi.nlm.nih.gov/pubmed/19948017", "http://www.ncbi.nlm.nih.gov/pubmed/27634906", "http://www.ncbi.nlm.nih.gov/pubmed/29727689", "http://www.ncbi.nlm.nih.gov/pubmed/26354892", "http://www.ncbi.nlm.nih.gov/pubmed/26813959", "http://www.ncbi.nlm.nih.gov/pubmed/28472085", "http://www.ncbi.nlm.nih.gov/pubmed/26671300", "http://www.ncbi.nlm.nih.gov/pubmed/23106814", "http://www.ncbi.nlm.nih.gov/pubmed/27312051" ], "ideal_answer": [ "The METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort aims at the integration of genomic and transcriptomic profiles of 2000 breast tumours." ], "type": "summary", "id": "5c6ffee17c78d6947100005a", "snippets": [ { "offsetInBeginSection": 846, "offsetInEndSection": 909, "text": "the METABRIC breast cancer data recorded for over 2000 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26132585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Predicting Outcomes of Hormone and Chemotherapy in the Molecular\u00a0Taxonomy of\u00a0Breast Cancer\u00a0International\u00a0Consortium (METABRIC) Study by Biochemically-inspired Machine Learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620450", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Genomic aberrations and gene expression-defined subtypes in the large METABRIC patient cohort have been used to stratify and predict survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Iteratively refining breast cancer intrinsic subtypes in the METABRIC dataset.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26770261", "endSection": "title" }, { "offsetInBeginSection": 355, "offsetInEndSection": 535, "text": "Towards the development of robust strategies, we designed an iterative approach to consistently discriminate intrinsic subtypes and improve class prediction in the METABRIC dataset", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26770261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Associations between genomic stratification of breast cancer and centrally reviewed tumour pathology in the METABRIC cohort.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29532008", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "The integration of genomic and transcriptomic profiles of 2000 breast tumours from the METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort revealed ten subtypes, termed integrative clusters (IntClust/s), characterised by distinct genomic drivers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29532008", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 1124, "text": "RESULTS\nWe show how this integration can be achieved automatically, following the declaration of appropriate metadata elements for each clinical data set; we demonstrate the practicality of this approach through application to experimental results and clinical data from five hospitals in the UK and Canada, undertaken as part of the METABRIC project (Molecular Taxonomy of Breast Cancer International Consortium).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948017", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1393, "text": "We apply and evaluate the approach by integrating the five different clinical datasets of METABRIC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948017", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 466, "text": "We had adopted a similar approach, termed 'BADGER', in the METABRIC project.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22912679", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 661, "text": "METABRIC is a large breast cancer study that may have been the first in which eQTL-based detection of mismatches was used during the study, rather than after the event, to aid quality assurance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22912679", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 476, "text": "We conducted a cis-expression quantitative trait loci (cis-eQTL) analysis using normal or tumor breast transcriptome data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), The Cancer Genome Atlas (TCGA), and the Genotype-Tissue Expression (GTEx) project.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29727689", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 673, "text": "We identified a total of 101 genes for 51 lead variants after combing the results of a meta-analysis of METABRIC and TCGA, and the results from GTEx at a Benjamini-Hochberg (BH)-adjusted p < 0.05.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29727689", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 729, "text": "In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30181556", "endSection": "abstract" }, { "offsetInBeginSection": 2453, "offsetInEndSection": 2874, "text": "Copy number aberration leading to SPAG5 gain or amplification and high SPAG5 transcript and SPAG5 protein concentrations were associated with shorter overall breast cancer-specific survival (METABRIC cohort [copy number aberration]: hazard ratio [HR] 1\u00b750, 95% CI 1\u00b718-1\u00b792, p=0\u00b700010; METABRIC cohort [transcript]: 1\u00b768, 1\u00b740-2\u00b701, p<0\u00b70001; and Nottingham-HES-breast cancer cohort [protein]: 1\u00b768, 1\u00b732-2\u00b712, p<0\u00b70001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27312051", "endSection": "abstract" }, { "offsetInBeginSection": 2875, "offsetInEndSection": 3255, "text": "In multivariable analysis, high SPAG5 transcript and SPAG5 protein expression were associated with reduced breast cancer-specific survival at 10 years compared with lower concentrations (Uppsala: HR 1\u00b762, 95% CI 1\u00b703-2\u00b753, p=0\u00b7036; METABRIC: 1\u00b727, 1\u00b702-1\u00b758, p=0\u00b7034; untreated lymph node-negative cohort: 2\u00b734, 1\u00b724-4\u00b742, p=0\u00b70090; and Nottingham-HES: 1\u00b773, 1\u00b723-2\u00b746, p=0\u00b70020).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27312051", "endSection": "abstract" }, { "offsetInBeginSection": 1680, "offsetInEndSection": 1825, "text": "The new subtypes show accurate distributions of current clinical markers ER, PR and HER2, and survival curves in the METABRIC and ROCK data sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26132585", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 806, "text": "The KMPlotter online tool, METABRIC and GSE25066 datasets were used to associate gene signatures with clinical outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28472085", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 535, "text": "Towards the development of robust strategies, we designed an iterative approach to consistently discriminate intrinsic subtypes and improve class prediction in the METABRIC dataset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26770261", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 640, "text": "METHODS\nThe EarlyR prognostic score was developed using integrative analysis of microarray data sets and formalin-fixed, paraffin-embedded-based quantitative real-time PCR assay and validated in Affymetrix data sets and METABRIC cohort using Cox proportional hazards models and Kaplan-Meier survival analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30097312", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 826, "text": "Classification of the personalized landscapes derived from 997 tumour samples within the Metabric discovery dataset reveals a novel poor prognosis cluster, reproducible in the 995-sample validation dataset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26813959", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 402, "text": "To explore the contribution of cellular metabolism to cancer heterogeneity, we analyse the Metabric dataset, a landmark genomic and transcriptomic study of 2,000 individual breast tumours, in the context of the human genome-scale metabolic network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26813959", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 822, "text": "We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634906", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 566, "text": "We obtained information regarding TP53 mutation and PAM50 subtypes in 699 tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26671300", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 707, "text": "METHODS We applied an artificial neural network-based integrative data mining approach to data from three cohorts of patients with breast cancer (the Nottingham discovery cohort (n=171), Uppsala cohort (n=249), and Molecular Taxonomy of Breast Cancer International Consortium [METABRIC] cohort; n=1980).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27312051", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1295, "text": "Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26354892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 405, "text": "Large research consortia such as the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), The Cancer Genome Atlas and International Cancer Genomics Consortium are systematically interrogating large sets of tumor samples through integrated analysis of genome-wide DNA copy number and promoter methylation, transcriptome-wide RNA expression, protein expression and exome-wide sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23106814", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 537, "text": "A recent METABRIC study explored the effects of cis-acting and trans-acting factors of gene expression regulation in breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23106814", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 373, "text": "Independent validation of prognostic interactions was achieved using data from the METABRIC study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30181556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "The Discovery of Novel Biomarkers Improves Breast Cancer Intrinsic Subtype Prediction and Reconciles the Labels in the METABRIC Data Set.The prediction of breast cancer intrinsic subtypes has been introduced as a valuable strategy to determine patient diagnosis and prognosis, and therapy response. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26132585", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Predicting Outcomes of Hormone and Chemotherapy in the Molecular\u00a0Taxonomy of\u00a0Breast Cancer\u00a0International\u00a0Consortium (METABRIC) Study by Biochemically-inspired Machine Learning.Genomic aberrations and gene expression-defined subtypes in the large METABRIC patient cohort have been used to stratify and predict survival. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620450", "endSection": "title" }, { "offsetInBeginSection": 519, "offsetInEndSection": 713, "text": "METABRIC is a large breast cancer study that may have been the first in which eQTL-based detection of mismatches was used during the study, rather than after the event, to aid quality assurance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22912679", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 1328, "text": "This may involve the integration of clinical data sets from several different sources: these data sets may employ different data definitions and some may be incomplete.
METHODS: In this work we employ semantic web techniques developed within the CancerGrid project, in particular the use of metadata elements and logic-based inference to annotate heterogeneous clinical information, integrate and query it.
RESULTS: We show how this integration can be achieved automatically, following the declaration of appropriate metadata elements for each clinical data set; we demonstrate the practicality of this approach through application to experimental results and clinical data from five hospitals in the UK and Canada, undertaken as part of the METABRIC project (Molecular Taxonomy of Breast Cancer International Consortium).
CONCLUSION: We describe a metadata approach for managing similarities and differences in clinical datasets in a standardized way that uses Common Data Elements (CDEs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948017", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1432, "text": "We apply and evaluate the approach by integrating the five different clinical datasets of METABRIC.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19948017", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 369, "text": "The present study used normalized gene expression signatures of paclitaxel drug response to predict outcome for different survival times in METABRIC patients receiving hormone (HT) and, in some cases, chemotherapy (CT) agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620450", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 619, "text": "We create personalized metabolic landscapes for each tumour by exploring sets of active reactions that satisfy constraints derived from human biochemistry and maximize congruency with the Metabric transcriptome data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26813959", "endSection": "abstract" } ] }, { "body": "Name 3 diseases for which lucatumumab is being tested?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24555495" ], "ideal_answer": [ "Lucatumumab is being tested as treatment for malignancies such as chronic lymphatic leukemia (CLL), Multiple Myeloma (MM), and non-Hodgkin's lymphoma (NHL)." ], "exact_answer": [ [ "chronic lymphatic leukemia" ], [ "multiple myeloma" ], [ "non-Hodgkin's lymphoma" ] ], "type": "list", "id": "5c654b3de842deac67000024", "snippets": [ { "offsetInBeginSection": 517, "offsetInEndSection": 731, "text": "Here, Dacetuzumab and Lucatumumab are in the most advanced stage and are being tested as treatment for malignancies such as chronic lymphatic leukemia (CLL), Multiple Myeloma (MM), and non-Hodgkin's lymphoma (NHL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555495", "endSection": "abstract" } ] }, { "body": "Which transcription factor binding site is contained in Alu repeats?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23771139", "http://www.ncbi.nlm.nih.gov/pubmed/21896491" ], "ideal_answer": [ "A novel abundant NF-\u03baB-binding site resides in specialized Alu-repetitive elements having the potential for long range transcription regulation, thus suggesting that in addition to its known role, NF-\u03baB has a primate-specific function and a role in human evolution.", "Remarkably, we identified a novel abundant NF-\u03baB-binding site residing in specialized Alu-repetitive elements having the potential for long range transcription regulation, thus suggesting that in addition to its known role, NF-\u03baB has a primate-specific function and a role in human evolution.", "Remarkably, we identified a novel abundant NF-\u03baB-binding site residing in specialized Alu-repetitive elements having the potential for long range transcription regulation, thus suggesting that in addition to its known role, NF-\u03baB has a primate-specific function and a role in human evolution. A de novo motif enrichment analysis uncovers secondary TFBSs (AP1, SP1) at characteristic distances from NF-\u03baB/RelA TFBSs." ], "exact_answer": [ "The NF-\u03baB-binding site" ], "type": "factoid", "id": "5c74111f7c78d694710000a1", "snippets": [ { "offsetInBeginSection": 502, "offsetInEndSection": 794, "text": "Remarkably, we identified a novel abundant NF-\u03baB-binding site residing in specialized Alu-repetitive elements having the potential for long range transcription regulation, thus suggesting that in addition to its known role, NF-\u03baB has a primate-specific function and a role in human evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896491", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 551, "text": "A de novo motif enrichment analysis uncovers secondary TFBSs (AP1, SP1) at characteristic distances from NF-\u03baB/RelA TFBSs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23771139", "endSection": "abstract" } ] }, { "body": "What is ferroptosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29127238", "http://www.ncbi.nlm.nih.gov/pubmed/29274359", "http://www.ncbi.nlm.nih.gov/pubmed/29175614", "http://www.ncbi.nlm.nih.gov/pubmed/28515173", "http://www.ncbi.nlm.nih.gov/pubmed/28494534" ], "ideal_answer": [ "Ferroptosis is a newly defined iron-dependent, non-apoptotic mode of cell death with necrotic morphology. Ferroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment" ], "type": "summary", "id": "5c5f218a1a4c55d80b00001b", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 176, "text": "Ferroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28494534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Ferroptosis is an iron-dependent form of regulated nonapoptotic cell death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28515173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Ferroptosis is a newly defined iron-dependent, non-apoptotic mode of cell death with necrotic morphology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29175614", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 239, "text": "Ferroptosis has recently been reported as a mechanism of iron-dependent nonapoptotic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29127238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29274359", "endSection": "abstract" } ] }, { "body": "What disease is treated with Laparoscopic Heller Myotomy (LHM)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29410262", "http://www.ncbi.nlm.nih.gov/pubmed/27338580", "http://www.ncbi.nlm.nih.gov/pubmed/30341655", "http://www.ncbi.nlm.nih.gov/pubmed/28472017", "http://www.ncbi.nlm.nih.gov/pubmed/26171430", "http://www.ncbi.nlm.nih.gov/pubmed/25783358", "http://www.ncbi.nlm.nih.gov/pubmed/27901639", "http://www.ncbi.nlm.nih.gov/pubmed/26108140", "http://www.ncbi.nlm.nih.gov/pubmed/27638274", "http://www.ncbi.nlm.nih.gov/pubmed/28145968", "http://www.ncbi.nlm.nih.gov/pubmed/28549006", "http://www.ncbi.nlm.nih.gov/pubmed/29218664" ], "ideal_answer": [ "To compare the outcome of per oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia", "Laparoscopic Heller myotomy (LHM) is the preferred surgical method for treating achalasia." ], "exact_answer": [ "achalasia" ], "type": "factoid", "id": "5c536b857e3cb0e23100001c", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 151, "text": " To compare the outcome of per oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28549006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Peroral endoscopic myotomy leads to higher rates of abnormal esophageal acid exposure than laparoscopic Heller myotomy in achalasia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30341655", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 155, "text": "Peroral endoscopic myotomy (POEM) is an emerging endoscopic treatment for achalasia and the long-term efficacy of POEM remains to be evaluated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28145968", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 269, "text": "This study compared the outcomes of POEM with that of the standard laparoscopic Heller myotomy (LHM) for achalasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28145968", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 501, "text": "The aim of this study was to compare robotic-assisted laparoscopic Heller myotomy (RAHM) with laparoscopic Heller myotomy (LHM) in terms of efficacy and safety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27638274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "AIMS AND OBJECTIVES\nLaparoscopic Heller myotomy (LHM) is the preferred surgical method for treating achalasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28472017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND AND AIM\nThis retrospective cohort study compared clinical outcomes and quality of life after peroral endoscopic myotomy (POEM) against laparoscopic Heller myotomy (LHM) for treatment of achalasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26108140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "INTRODUCTION\nAchalasia is a rare disorder in children who are commonly treated by laparoscopic Heller's myotomy (LHM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27901639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "AIMS AND OBJECTIVES Laparoscopic Heller myotomy (LHM) is the preferred surgical method for treating achalasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28472017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND AND AIM This retrospective cohort study compared clinical outcomes and quality of life after peroral endoscopic myotomy (POEM) against laparoscopic Heller myotomy (LHM) for treatment of achalasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26108140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "OBJECTIVE To compare the outcome of per oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28549006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND Per oral endoscopic myotomy (POEM) has recently emerged as a viable option relative to the classic approach of laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29218664", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 342, "text": "Although laparoscopic Heller myotomy (LHM) is the current gold standard management for type III achalasia, peroral endoscopic myotomy (POEM) is conceivably superior because it allows for a longer myotomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26171430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Laparoscopic Heller Myotomy Versus Peroral Endoscopic Myotomy (POEM) for Achalasia: A Systematic Review and Meta-analysis.To compare the outcome of per oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28549006", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Reduced postoperative pain scores and narcotic use favor per-oral endoscopic myotomy over laparoscopic Heller myotomy.Per-oral endoscopic myotomy (POEM) is a less invasive therapy for achalasia with a shorter hospitalization but with similar short- and long-term outcomes as a laparoscopic Heller myotomy (LHM). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27338580", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 289, "text": "Laparoscopic Heller myotomy (LHM) represents the treatment of choice in young patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25783358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Systematic Review and Meta-Analysis of Perioperative Outcomes of Peroral Endoscopic Myotomy (POEM) and Laparoscopic Heller Myotomy (LHM) for Achalasia.Laparoscopic Heller myotomy (LHM) is the preferred surgical method for treating achalasia. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28472017", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "Comparison of early outcomes and quality of life after laparoscopic Heller's cardiomyotomy to peroral endoscopic myotomy for treatment of achalasia.This retrospective cohort study compared clinical outcomes and quality of life after peroral endoscopic myotomy (POEM) against laparoscopic Heller myotomy (LHM) for treatment of achalasia. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26108140", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "Laparoscopic Heller Myotomy vs Per Oral Endoscopic Myotomy: Patient-Reported Outcomes at a Single Institution.Although laparoscopic Heller myotomy (LHM) has been the standard of care for achalasia, per oral endoscopic myotomy (POEM) has gained popularity as a viable alternative. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29410262", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Outcome of Peroral Endoscopic Myotomy (POEM) for Treating Achalasia Compared With Laparoscopic Heller Myotomy (LHM).Peroral endoscopic myotomy (POEM) is an emerging endoscopic treatment for achalasia and the long-term efficacy of POEM remains to be evaluated. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28145968", "endSection": "title" }, { "offsetInBeginSection": 316, "offsetInEndSection": 431, "text": "This study compared the outcomes of POEM with that of the standard laparoscopic Heller myotomy (LHM) for achalasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28145968", "endSection": "abstract" } ] }, { "body": "Name 4 side effects of enasidenib", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30360730" ], "ideal_answer": [ "Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels etc." ], "exact_answer": [ [ "elevated bilirubin levels" ], [ "diarrhea" ], [ "decreased potassium levels" ], [ "decreased calcium levels" ] ], "type": "list", "id": "5c658a8f7c78d69471000007", "snippets": [ { "offsetInBeginSection": 1517, "offsetInEndSection": 1693, "text": "Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360730", "endSection": "abstract" } ] }, { "body": "Is lucatumumab a polyclonal antibody?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22861192" ], "ideal_answer": [ "No, lucatumumab is a a monoclonal antibody against CD40." ], "exact_answer": "no", "type": "yesno", "id": "5c6582207c78d69471000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "A phase 1 study of lucatumumab, a fully human anti-CD40 antagonist monoclonal antibody administered intravenously to patients with relapsed or refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22861192", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "In this open-label, multicentre, phase 1 study a fully human anti-CD40 antagonist monoclonal antibody, lucatumumab, was evaluated in patients with relapsed/refractory multiple myeloma (MM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22861192", "endSection": "abstract" } ] }, { "body": "What is evaluated with the SAD PERSONS scale?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "http://www.ncbi.nlm.nih.gov/pubmed/21546092", "http://www.ncbi.nlm.nih.gov/pubmed/29699523", "http://www.ncbi.nlm.nih.gov/pubmed/26346049", "http://www.ncbi.nlm.nih.gov/pubmed/24533537", "http://www.ncbi.nlm.nih.gov/pubmed/29665120", "http://www.ncbi.nlm.nih.gov/pubmed/28471534", "http://www.ncbi.nlm.nih.gov/pubmed/28302702", "http://www.ncbi.nlm.nih.gov/pubmed/28723978", "http://www.ncbi.nlm.nih.gov/pubmed/24884399" ], "ideal_answer": [ "SAD PERSONS scale was developed to evaluate suicide risk." ], "exact_answer": [ "suicide risk" ], "type": "factoid", "id": "5c73ad027c78d6947100008d", "snippets": [ { "offsetInBeginSection": 330, "offsetInEndSection": 582, "text": "METHOD: We compared the predictive accuracy of the Manchester Self-Harm Rule (MSHR), ReACT Self-Harm Rule (ReACT), SAD PERSONS Scale (SPS) and Modified SAD PERSONS Scale (MSPS) in an unselected sample of patients attending hospital following self-harm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29699523", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 653, "text": "Clinicians completed a standard suicide risk instrument (modified SAD PERSONS scale), a 10-point Likert scale assessment of judgment of patient suicide risk (Clinician Prediction Scale), and a measure of their emotional responses to the patient (Therapist Response Questionnaire-Suicide Form). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29665120", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 412, "text": "AimsTo evaluate the performance of risk scales (Manchester Self-Harm Rule, ReACT Self-Harm Rule, SAD PERSONS scale, Modified SAD PERSONS scale, Barratt Impulsiveness Scale); and patient and clinician estimates of risk in identifying patients who repeat self-harm within 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28302702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Predicting suicide with the SAD PERSONS scale.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471534", "endSection": "title" }, { "offsetInBeginSection": 128, "offsetInEndSection": 382, "text": "The SAD PERSONS suicide risk assessment scale is widely implemented in clinical settings despite limited supporting evidence. This article aims to determine the ability of the SAD PERSONS scale (SPS) to predict future suicide in the emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471534", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1603, "text": "CONCLUSIONS: Although widely used in educational and clinical settings, these findings do not support the use of the SPS and Modified SPS to predict suicide in adults seen by psychiatric services in the emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471534", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1206, "text": " For the outcome suicide attempt SAD PERSONS Scale had a sensitivity of 15% (95% CI 8-24) and specificity of 97% (96-98), and the Manchester Self-Harm Rule (MSHR) a sensitivity of 97% (97-97) and a specificity of 20% (20-21). ReACT, which is a modification of MSHR, had a similar low specificity, as did the Sodersjukhuset Self Harm Rule. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28723978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "OBJECTIVE\nThe SAD PERSONS scale is a widely used risk assessment tool for suicidal behavior despite a paucity of supporting data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1442, "text": "SAD PERSONS did not predict suicide attempts better than chance (area under the curve =0.572; 95% confidence interval [CI], 0.51-0.64; P value nonsignificant).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "abstract" }, { "offsetInBeginSection": 1780, "offsetInEndSection": 1885, "text": "CONCLUSION\nIn their current form, SAD PERSONS and MSPS do not accurately predict future suicide attempts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "abstract" }, { "offsetInBeginSection": 1767, "offsetInEndSection": 1896, "text": "CONCLUSIONS\nThe Chinese SAD PERSONS Scale is a brief instrument with acceptable psychometric properties for self-harm prediction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24533537", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 252, "text": "The SAD PERSONS suicide risk assessment scale is widely implemented in clinical settings despite limited supporting evidence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "OBJECTIVE The SAD PERSONS scale is a widely used risk assessment tool for suicidal behavior despite a paucity of supporting data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "abstract" }, { "offsetInBeginSection": 1767, "offsetInEndSection": 1896, "text": "CONCLUSIONS The Chinese SAD PERSONS Scale is a brief instrument with acceptable psychometric properties for self-harm prediction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24533537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The SAD PERSONS scale (SPS) is widely used for suicide risk assessment in clinical and educational settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884399", "endSection": "abstract" }, { "offsetInBeginSection": 765, "offsetInEndSection": 929, "text": "Beck's Medical Lethality Scale (BMLS) was administered to assess the degree of medical injury, and the SAD PERSONS mnemonic scale was used to evaluate suicide risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21546092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The SAD PERSONS scale for suicide risk assessment: a systematic review.The SAD PERSONS scale (SPS) is widely used for suicide risk assessment in clinical and educational settings. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884399", "endSection": "title" }, { "offsetInBeginSection": 195, "offsetInEndSection": 320, "text": "The SAD PERSONS suicide risk assessment scale is widely implemented in clinical settings despite limited supporting evidence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471534", "endSection": "abstract" }, { "offsetInBeginSection": 2048, "offsetInEndSection": 2225, "text": "The Chinese SAD PERSONS Scale is a brief instrument with acceptable psychometric properties for self-harm prediction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24533537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Predicting suicide attempts with the SAD PERSONS scale: a longitudinal analysis.The SAD PERSONS scale is a widely used risk assessment tool for suicidal behavior despite a paucity of supporting data. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Predicting suicide with the SAD PERSONS scale.Suicide is a major public health issue, and a priority requirement is accurately identifying high-risk individuals. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471534", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 720, "text": "Subjects completed a series of depression/suicide screening tools: the Columbia Suicide Severity Scale, SAD PERSONS scale, Patient Health Questionnaire 9, and Beck Scale for Suicidal Ideation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: The SAD PERSONS scale is a widely used risk assessment tool for suicidal behavior despite a paucity of supporting data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1136, "text": "Both SAD PERSONS and MSPS showed poor predictive ability for future suicide attempts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1468, "text": "SAD PERSONS did not predict suicide attempts better than chance (area under the curve =0.572; 95% confidence interval [CI], 0.51-0.64; P value nonsignificant).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795212", "endSection": "abstract" } ] }, { "body": "Briefly describe a deep learning system that is more accurate than human experts at detecting melanoma.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29439500", "http://www.ncbi.nlm.nih.gov/pubmed/28969863", "http://www.ncbi.nlm.nih.gov/pubmed/29428356", "http://www.ncbi.nlm.nih.gov/pubmed/29846502", "http://www.ncbi.nlm.nih.gov/pubmed/29047032", "http://www.ncbi.nlm.nih.gov/pubmed/28026754", "http://www.ncbi.nlm.nih.gov/pubmed/29266819" ], "ideal_answer": [ "in August of 2018 a study was published where a Convolutional Neural Network's (CNN) diagnostic performance was compared with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN, the CNN had both higher sensitivity and specificity." ], "type": "summary", "id": "5c5245b57e3cb0e23100000a", "snippets": [ { "offsetInBeginSection": 63, "offsetInEndSection": 278, "text": "Computer-aided diagnosis systems powered by convolutional neural networks (CNNs) can improve diagnostic accuracy and save lives. CNNs have been successfully used in both skin lesion segmentation and classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Machine learning-based diagnosis of melanoma using macro images", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29266819", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "We tested the use of a deep learning algorithm to classify the clinical images of 12 skin diseases-basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, actinic keratosis, seborrheic keratosis, malignant melanoma, melanocytic nevus, lentigo, pyogenic granuloma, hemangioma, dermatofibroma, and wart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29428356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Skin Lesion Analysis towards Melanoma Detection Using Deep Learning Network.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29439500", "endSection": "title" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1602, "text": "Deep learning computer vision systems classified melanoma dermoscopy images with accuracy that exceeded some but not all dermatologists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28969863", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 164, "text": "diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846502", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 97, "text": "Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846502", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 441, "text": "In order to meet these challenges, we propose a novel method for melanoma recognition by leveraging very deep convolutional neural networks (CNNs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28026754", "endSection": "abstract" } ] }, { "body": "Which human disease is experimental autoimmune encephalomyelitis (EAE) model for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27758698", "http://www.ncbi.nlm.nih.gov/pubmed/30385269", "http://www.ncbi.nlm.nih.gov/pubmed/27377536", "http://www.ncbi.nlm.nih.gov/pubmed/27996890" ], "ideal_answer": [ "Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS (Multiple Sclerosis)." ], "exact_answer": [ "Model of MS (Multiple Sclerosis)" ], "type": "factoid", "id": "5c783d32d774d04240000004", "snippets": [ { "offsetInBeginSection": 307, "offsetInEndSection": 377, "text": "experimental autoimmune encephalomyelitis (EAE), an animal model of MS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27377536", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 319, "text": "xperimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27996890", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 787, "text": "relapsing MS and its model, experimental autoimmune encephalomyelitis (EAE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27758698", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 514, "text": "experimental autoimmune encephalomyelitis (EAE), an animal model of MS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30385269", "endSection": "abstract" } ] }, { "body": "What is the cause if the rare disease cystinosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29416314", "http://www.ncbi.nlm.nih.gov/pubmed/29421779", "http://www.ncbi.nlm.nih.gov/pubmed/29467429" ], "ideal_answer": [ "Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene." ], "exact_answer": [ "Mutations in the cystinosin lysosomal cystine transporter (CTNS) gene" ], "type": "factoid", "id": "5c76d0417c78d694710000a8", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Cystinosis is a rare, autosomal recessive disorder leading to defective transport of cystine out of lysosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29416314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29421779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Cystinosin, a lysosomal transporter is involved in the efflux of cystine from the lysosome to the cytosol. Mutations in the human cystinosin gene (CTNS) cause cystinosis, a recessive autosomal disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29467429", "endSection": "abstract" } ] }, { "body": "Is lithium effective for treatment of amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23453347", "http://www.ncbi.nlm.nih.gov/pubmed/26892289", "http://www.ncbi.nlm.nih.gov/pubmed/22091594", "http://www.ncbi.nlm.nih.gov/pubmed/21936930", "http://www.ncbi.nlm.nih.gov/pubmed/29399045", "http://www.ncbi.nlm.nih.gov/pubmed/22378918", "http://www.ncbi.nlm.nih.gov/pubmed/29400298", "http://www.ncbi.nlm.nih.gov/pubmed/18367867", "http://www.ncbi.nlm.nih.gov/pubmed/18250315", "http://www.ncbi.nlm.nih.gov/pubmed/20702794", "http://www.ncbi.nlm.nih.gov/pubmed/23582371", "http://www.ncbi.nlm.nih.gov/pubmed/28978660", "http://www.ncbi.nlm.nih.gov/pubmed/20363190" ], "ideal_answer": [ "No, lithium is not effective for treatment of amyotrophic lateral sclerosis." ], "exact_answer": "no", "type": "yesno", "id": "5c662c507c78d6947100000d", "snippets": [ { "offsetInBeginSection": 125, "offsetInEndSection": 331, "text": "In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29399045", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1343, "text": "Despite several positive case reports and short studies, further controlled researches have failed to substantiate any positive effects of lithium exposure in amyotrophic lateral sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29400298", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1211, "text": "The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28978660", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1174, "text": "Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26892289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND\nLithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23453347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "In a pilot clinical study that we recently published we found that lithium administration slows the progression of Amyotrophic Lateral Sclerosis (ALS) in human patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18367867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23453347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "BACKGROUND A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Lithium delays progression of amyotrophic lateral sclerosis.ALS is a devastating neurodegenerative disorder with no effective treatment. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250315", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 395, "text": "Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23453347", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "INTRODUCTION: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582371", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1643, "text": "A recently published study also ruled out any possible modest effect.
CONCLUSIONS: There is evidence to suggest that lithium has no short-term benefits in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582371", "endSection": "abstract" }, { "offsetInBeginSection": 1644, "offsetInEndSection": 1898, "text": "A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582371", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 519, "text": "None of the patients treated with lithium died during the 15 months of the follow-up, and disease progression was markedly attenuated when compared with age-, disease duration-, and sex-matched control patients treated with riluzole for the same amount of time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18250315", "endSection": "abstract" } ] }, { "body": "Should dacomitinib be used for treatment of glioblastoma patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28575464", "http://www.ncbi.nlm.nih.gov/pubmed/30247945" ], "ideal_answer": [ "No, dacomitinib has a limited single-agent activity in recurrent glioblastoma with EGFR amplification." ], "exact_answer": "no", "type": "yesno", "id": "5c73acea7c78d69471000085", "snippets": [ { "offsetInBeginSection": 1003, "offsetInEndSection": 1150, "text": "Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30247945", "endSection": "abstract" }, { "offsetInBeginSection": 1498, "offsetInEndSection": 1599, "text": "Conclusions: Dacomitinib has a limited single-agent activity in recurrent GB with EGFR amplification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28575464", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1135, "text": "Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30247945", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1156, "text": "Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30247945", "endSection": "abstract" } ] }, { "body": "Which molecular does daratumumab target?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29500635" ], "ideal_answer": [ "Daratumumab is an anti-CD38 antibody." ], "exact_answer": [ "CD38" ], "type": "factoid", "id": "5c6545bae842deac6700001d", "snippets": [ { "offsetInBeginSection": 875, "offsetInEndSection": 1076, "text": "The addition of daratumumab (anti-CD38 antibody) augmented NK-cell cytotoxicity against target cells expressing high CD38, but not against CD38 low or negative target cells also in the presence of TME.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29500635", "endSection": "abstract" } ] }, { "body": "What is etarfolatide used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26238440", "http://www.ncbi.nlm.nih.gov/pubmed/24667717", "http://www.ncbi.nlm.nih.gov/pubmed/25457975", "http://www.ncbi.nlm.nih.gov/pubmed/27084348", "http://www.ncbi.nlm.nih.gov/pubmed/24742319", "http://www.ncbi.nlm.nih.gov/pubmed/24127448" ], "ideal_answer": [ "Etarfolatide in the form of 99mTc-etarfolatide is used as a companion imaging agent" ], "exact_answer": [ "companion imaging agent" ], "type": "factoid", "id": "5c7161f47c78d69471000066", "snippets": [ { "offsetInBeginSection": 26, "offsetInEndSection": 109, "text": "99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26238440", "endSection": "title" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1452, "text": " In contrast, the noninvasive single-photon emission computed tomography-based companion imaging agent, (99m)Tc-etarfolatide ((99m)Tc-EC20), is in development for use as a companion diagnostic with the FR\u03b1-targeted folate conjugate,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25457975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "OBJECTIVE\nTechnetium etarfolatide ((99m)Tc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26238440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "OBJECTIVE\nThrough binding to folate receptor-\u03b2 (FR-\u03b2), the new (99m)Tc-EC20 (Etarfolatide) imaging technique detects activated but not resting macrophages in\u00a0vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27084348", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1520, "text": "In contrast, the noninvasive single-photon emission computed tomography-based companion imaging agent, (99m)Tc-etarfolatide ((99m)Tc-EC20), is in development for use as a companion diagnostic with the FR\u03b1-targeted folate conjugate, vintafolide (EC145), to identify patients whose tumors express FR\u03b1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25457975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "OBJECTIVE Technetium etarfolatide ((99m)Tc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26238440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 481, "text": "Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide).This report examines (99m)Tc-etarfolatide imaging to identify the presence of folate receptor (FR) on tumors of women with recurrent/refractory ovarian or endometrial cancer and correlates expression with response to FR-targeted therapy (vintafolide). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667717", "endSection": "title" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1607, "text": "In contrast, the noninvasive single-photon emission computed tomography-based companion imaging agent, (99m)Tc-etarfolatide ((99m)Tc-EC20), is in development for use as a companion diagnostic with the FR\u03b1-targeted folate conjugate, vintafolide (EC145), to identify patients whose tumors express FR\u03b1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25457975", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 929, "text": "We review the development of vintafolide (EC145), a folic acid-desacetylvinblastine conjugate, the predictive utility of a FR-targeted imaging agent, technetium-(99)m-etarfolatide (EC20), the challenges in proving survival advantage, and other approaches to exploiting FR as a target in ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24742319", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 700, "text": "The utility of an FR-targeted imaging agent, (99m)Tc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24127448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 457, "text": "BACKGROUND: This report examines (99m)Tc-etarfolatide imaging to identify the presence of folate receptor (FR) on tumors of women with recurrent/refractory ovarian or endometrial cancer and correlates expression with response to FR-targeted therapy (vintafolide).
PATIENTS AND METHODS: In this phase II, single-arm, multicenter study, patients with advanced ovarian cancer were imaged with (99m)Tc-etarfolatide before vintafolide treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667717", "endSection": "abstract" } ] }, { "body": "What is the function of Plasminogen activator inhibitor 1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29454747", "http://www.ncbi.nlm.nih.gov/pubmed/29967603", "http://www.ncbi.nlm.nih.gov/pubmed/29228113" ], "ideal_answer": [ "Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis." ], "exact_answer": [ "PAI-1 is important in fibrinolysis." ], "type": "factoid", "id": "5c5f264b1a4c55d80b00001e", "snippets": [ { "offsetInBeginSection": 142, "offsetInEndSection": 309, "text": "Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454747", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1124, "text": " Plasminogen activator inhibitor-1 (PAI-1), the gene product of SERPINE1, inhibited cell adhesion, suggesting that PAI-1, like THBS1, has anti-angiogenic properties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29228113", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 207, "text": "Plasminogen activator inhibitor-1 (PAI-1), a crucial regulator of fibrinolysis, is increased in sepsis, but its values in predicting disease severity or mortality outcomes have been controversial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967603", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of durvalumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29258079", "http://www.ncbi.nlm.nih.gov/pubmed/29416316", "http://www.ncbi.nlm.nih.gov/pubmed/29545095", "http://www.ncbi.nlm.nih.gov/pubmed/28960263", "http://www.ncbi.nlm.nih.gov/pubmed/28831813", "http://www.ncbi.nlm.nih.gov/pubmed/30013326", "http://www.ncbi.nlm.nih.gov/pubmed/30489337", "http://www.ncbi.nlm.nih.gov/pubmed/28885881", "http://www.ncbi.nlm.nih.gov/pubmed/28471727", "http://www.ncbi.nlm.nih.gov/pubmed/29517083", "http://www.ncbi.nlm.nih.gov/pubmed/27265743", "http://www.ncbi.nlm.nih.gov/pubmed/29069302", "http://www.ncbi.nlm.nih.gov/pubmed/28705024", "http://www.ncbi.nlm.nih.gov/pubmed/28643244", "http://www.ncbi.nlm.nih.gov/pubmed/28403786", "http://www.ncbi.nlm.nih.gov/pubmed/29958099", "http://www.ncbi.nlm.nih.gov/pubmed/30383184", "http://www.ncbi.nlm.nih.gov/pubmed/29773326", "http://www.ncbi.nlm.nih.gov/pubmed/26858122", "http://www.ncbi.nlm.nih.gov/pubmed/29140105", "http://www.ncbi.nlm.nih.gov/pubmed/28717238", "http://www.ncbi.nlm.nih.gov/pubmed/30514390", "http://www.ncbi.nlm.nih.gov/pubmed/29486607" ], "ideal_answer": [ "Durvalumab is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. It is Immune checkpoint inhibitor used of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1." ], "type": "summary", "id": "5c66329e7c78d6947100000f", "snippets": [ { "offsetInBeginSection": 1048, "offsetInEndSection": 1253, "text": "In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30489337", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1017, "text": "Ipilimumab (anti-CTLA-4) is the godfather of checkpoint inhibitors, whereas several blocking monoclonal antibodies targeting PD-1 (nivolumab and pembrolizumab) and PD-L1 (atezolizumab, durvalumab, avelumab, and BMS-946559) have been developed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28403786", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 1120, "text": "DATA SYNTHESIS: Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28831813", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 728, "text": "METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. A formal systematic analysis was conducted with Comprehensive Meta-Analysis software (version 2.2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29140105", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 662, "text": "However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28717238", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 867, "text": "Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28717238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28717238", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 429, "text": "We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471727", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 252, "text": "Combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab might provide greater antitumour activity than either drug alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26858122", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 409, "text": "Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29958099", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 778, "text": "The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29416316", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 363, "text": "Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30514390", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 391, "text": "Other notable PD-L1 inhibitors under development include avelumab and durvalumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28705024", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 541, "text": "Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27265743", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 673, "text": "Five antibodies targeting the programmed cell death protein 1--programmed cell death 1 ligand 1 (PD-1--PD-L1) pathway have been approved by the U.S. Food and Drug Administration (FDA) for the management of various malignancies: pembrolizumab, nivolumab, atezolizumab, durvalumab and avelumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29517083", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1075, "text": "Currently, the only FDA-approved indication for the anti-PD-L1 monoclonal antibody durvalumab (MEDI-4736) is locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-based chemotherapy within 12 months of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29517083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Intravenous durvalumab (Imfinzi\u2122; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28643244", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 393, "text": "Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30013326", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 704, "text": "We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471727", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28717238", "endSection": "title" }, { "offsetInBeginSection": 760, "offsetInEndSection": 964, "text": "Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28717238", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 379, "text": "Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.
Methods: A systematic search of PubMed, Embase, and related articles was performed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30013326", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 430, "text": "Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29958099", "endSection": "abstract" } ] }, { "body": "Which tool has been developed for GPU-accelerated alignment of bisulfite-treated DNA sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29554207" ], "ideal_answer": [ "The alignment of bisulfite-treated DNA sequences (BS-seq reads) to a large genome involves a significant computational burden beyond that required to align non-bisulfite-treated reads. In the analysis of BS-seq data, this can present an important performance bottleneck that can be mitigated by appropriate algorithmic and software-engineering improvements. One strategy is to modify the read-alignment algorithms by integrating the logic related to BS-seq alignment, with the goal of making the software implementation amenable to optimizations that lead to higher speed and greater sensitivity than might otherwise be attainable. This strategy was evaluated using Arioc, a short-read aligner that uses GPU (general-purpose graphics processing unit) hardware to accelerate computationally-expensive programming logic." ], "exact_answer": [ "Arioc" ], "type": "factoid", "id": "5c6aef167c78d69471000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Arioc: GPU-accelerated alignment of short bisulfite-treated reads.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554207", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1353, "text": "The alignment of bisulfite-treated DNA sequences (BS-seq reads) to a large genome involves a significant computational burden beyond that required to align non-bisulfite-treated reads. In the analysis of BS-seq data, this can present an important performance bottleneck that can be mitigated by appropriate algorithmic and software-engineering improvements. One strategy is to modify the read-alignment algorithms by integrating the logic related to BS-seq alignment, with the goal of making the software implementation amenable to optimizations that lead to higher speed and greater sensitivity than might otherwise be attainable.Results: We evaluated this strategy using Arioc, a short-read aligner that uses GPU (general-purpose graphics processing unit) hardware to accelerate computationally-expensive programming logic. We integrated the BS-seq computational logic into both GPU and CPU code throughout the Arioc implementation. We then carried out a read-by-read comparison of Arioc's reported alignments with the alignments reported by well-known CPU-based BS-seq read aligners. With simulated reads, Arioc's accuracy is equal to or better than the other read aligners we evaluated. With human sequencing reads, Arioc's throughput is at least 10 times faster than existing BS-seq aligners across a wide range of sensitivity settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554207", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 838, "text": "Results\nWe evaluated this strategy using Arioc, a short-read aligner that uses GPU (general-purpose graphics processing unit) hardware to accelerate computationally-expensive programming logic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554207", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1099, "text": "We then carried out a read-by-read comparison of Arioc's reported alignments with the alignments reported by well-known CPU-based BS-seq read aligners.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554207", "endSection": "abstract" } ] }, { "body": "Which disease is gemtuzumab ozogamicin used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29172076" ], "ideal_answer": [ "Gemtuzumab ozogamicin is used for the treatment of acute myeloid leukemia" ], "exact_answer": [ "Acute myeloid leukemia" ], "type": "factoid", "id": "5c646fd3e842deac6700001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29172076", "endSection": "abstract" } ] }, { "body": "What is GeneWeaver used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24233775", "http://www.ncbi.nlm.nih.gov/pubmed/26834590", "http://www.ncbi.nlm.nih.gov/pubmed/26092690", "http://www.ncbi.nlm.nih.gov/pubmed/22080549", "http://www.ncbi.nlm.nih.gov/pubmed/24731198", "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "http://www.ncbi.nlm.nih.gov/pubmed/25374613", "http://www.ncbi.nlm.nih.gov/pubmed/26656951", "http://www.ncbi.nlm.nih.gov/pubmed/23195309", "http://www.ncbi.nlm.nih.gov/pubmed/24923803" ], "ideal_answer": [ "GeneWeaver: a web-based system for integrative functional genomics.", "GeneWeaver is a freely available resource for storing, curating and analyzing sets of genes from heterogeneous data sources. GeneWeaver enables researchers to store, share, analyze, and compare results of their own genome-wide functional genomics experiments in an environment containing rich companion data obtained from major curated repositories, including the Mouse Genome Database and other model organism databases, along with derived data from highly specialized resources, publications, and user submissions.", "GeneWeaver: a web-based system for integrative functional genomics. The freely available GeneWeaver (http://www.GeneWeaver.org) powered by the Ontological Discovery Environment is a curated repository of genomic experimental results with an accompanying tool set for dynamic integration of these data sets, enabling users to interactively address questions about sets of biological functions and their relations to sets of genes. The GeneWeaver.org system provides a platform for cross-species integration and interrogation of heterogeneous curated and experimentally derived functional genomics data." ], "type": "summary", "id": "5c6fff2e7c78d6947100005b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "GeneWeaver: a web-based system for integrative functional genomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080549", "endSection": "title" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1233, "text": "The freely available GeneWeaver (http://www.GeneWeaver.org) powered by the Ontological Discovery Environment is a curated repository of genomic experimental results with an accompanying tool set for dynamic integration of these data sets, enabling users to interactively address questions about sets of biological functions and their relations to sets of genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080549", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 507, "text": "The GeneWeaver.org system provides a platform for cross-species integration and interrogation of heterogeneous curated and experimentally derived functional genomics data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26092690", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 899, "text": "GeneWeaver enables researchers to store, share, analyze, and compare results of their own genome-wide functional genomics experiments in an environment containing rich companion data obtained from major curated repositories, including the Mouse Genome Database and other model organism databases, along with derived data from highly specialized resources, publications, and user submissions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26092690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The GeneWeaver data and analytics website (www.geneweaver.org) is a publically available resource for storing, curating and analyzing sets of genes from heterogeneous data sources.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656951", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1200, "text": "GeneWeaver empowers users with the ability to construct data driven descriptions of shared and unique biological processes, diseases and traits within and across species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656951", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 602, "text": "Our interactive web-based software system, Gene Weaver (http://www.geneweaver.org), couples curated results from genomic studies to graph-theoretical tools for combinatorial analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26834590", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 533, "text": "GeneWeaver is an online database and suite of tools at www.geneweaver.org that allows for fast aggregation and analysis of gene set-centric data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1187, "text": "Here we use GeneWeaver to find genes common to multiple gene sets, prioritize candidate genes from a quantitative trait locus, and characterize a set of differentially expressed genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 841, "text": "These can be entered directly into GeneWeaver or transferred from widely used resources such as GeneNetwork.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 728, "text": "GeneWeaver contains curated experimental data together with resource-level data such as GO annotations, MP annotations, and KEGG pathways, along with persistent stores of user entered data sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1200, "text": "By enumerating the common and distinct biological molecules associated with all subsets of curated or user submitted groups of gene sets and gene networks, GeneWeaver empowers users with the ability to construct data driven descriptions of shared and unique biological processes, diseases and traits within and across species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The GeneWeaver bipartite data model provides an efficient means to evaluate shared molecular components from sets derived across diverse species, disease states and biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25374613", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1049, "text": "Interrogating common relationships among biological networks and conventional GeneWeaver gene lists will increase functional specificity and reliability of the shared biological components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25374613", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 603, "text": "Our interactive web-based software system, Gene Weaver (http://www.geneweaver.org), couples curated results from genomic studies to graph-theoretical tools for combinatorial analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26834590", "endSection": "abstract" }, { "offsetInBeginSection": 1581, "offsetInEndSection": 1757, "text": "A robust implementation has been incorporated into GeneWeaver, an online tool for integrating and analyzing functional genomics experiments, available at http://geneweaver.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731198", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 959, "text": "The GeneWeaver web-based software system brings together a large data archive from diverse functional genomics data with a suite of combinatorial tools in an interactive environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24233775", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 361, "text": "Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24923803", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 526, "text": "Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with &gt;60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24923803", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 912, "text": "These can be entered directly into GeneWeaver or transferred from widely used resources such as GeneNetwork.org. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "endSection": "abstract" }, { "offsetInBeginSection": 1878, "offsetInEndSection": 2054, "text": "A robust implementation has been incorporated into GeneWeaver, an online tool for integrating and analyzing functional genomics experiments, available at http://geneweaver.org. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731198", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1300, "text": "The freely available GeneWeaver (http://www.GeneWeaver.org) powered by the Ontological Discovery Environment is a curated repository of genomic experimental results with an accompanying tool set for dynamic integration of these data sets, enabling users to interactively address questions about sets of biological functions and their relations to sets of genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22080549", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 661, "text": "GeneWeaver.org is a web-based software system that employs many of these techniques and has been used in the study of complex behavior and addiction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23195309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "GeneWeaver: data driven alignment of cross-species genomics in biology and disease.The GeneWeaver data and analytics website (www.geneweaver.org) is a publically available resource for storing, curating and analyzing sets of genes from heterogeneous data sources. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656951", "endSection": "title" }, { "offsetInBeginSection": 605, "offsetInEndSection": 799, "text": "GeneWeaver contains curated experimental data together with resource-level data such as GO annotations, MP annotations, and KEGG pathways, along with persistent stores of user entered data sets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 645, "text": "Since the previous review in the 2012 Nucleic Acids Research Database issue, GeneWeaver's underlying analytics platform has been enhanced, its number and variety of publically available gene set data sources has been increased, and its advanced search mechanisms have been expanded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656951", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 967, "text": "A search of over 60,000 gene sets in GeneWeaver's database revealed alcohol-related experimental results including genes identified in mouse genetic mapping studies, alcohol selected Drosophila lines, Rattus differential expression, and human alcoholic brains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26834590", "endSection": "abstract" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1783, "text": "A robust implementation has been incorporated into GeneWeaver, an online tool for integrating and analyzing functional genomics experiments, available at http://geneweaver.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24731198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Integrative Functional Genomics for Systems Genetics in GeneWeaver.org.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933523", "endSection": "title" } ] }, { "body": "Are there ultraconserved regions in the budding yeast (Saccharomyces cerevisiae)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028909" ], "ideal_answer": [ "Yes. In addition to some fundamental biological functions, ultraconserved regions play an important role in the adaptation of Saccharomyces cerevisiae to the acidic environment." ], "exact_answer": "yes", "type": "yesno", "id": "5c6d7bb57c78d6947100003b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The systematic analysis of ultraconserved genomic regions in the budding yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1147, "text": "In the evolution of species, a kind of special sequences, termed ultraconserved sequences (UCSs), have been inherited without any change, which strongly suggests those sequences should be crucial for the species to survive or adapt to the environment. However, the UCSs are still regarded as mysterious genetic sequences so far. Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.Results: Our results indicate that, in addition to some fundamental biological functions, the UCSs play an important role in the adaptation of Saccharomyces cerevisiae to the acidic environment, which is backed up by the previous observation. Besides that, we also find the highly unchanged genes are enriched in some other pathways, such as the nutrient-sensitive signaling pathway. To facilitate the investigation of unique UCSs, the UCSC Genome Browser was utilized to visualize the chromosomal position and related annotations of UCSs in S.cerevisiae genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 584, "text": "Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Motivation\nIn the evolution of species, a kind of special sequences, termed ultraconserved sequences (UCSs), have been inherited without any change, which strongly suggests those sequences should be crucial for the species to survive or adapt to the environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "The systematic analysis of ultraconserved genomic regions in the budding yeast.In the evolution of species, a kind of special sequences, termed ultraconserved sequences (UCSs), have been inherited without any change, which strongly suggests those sequences should be crucial for the species to survive or adapt to the environment. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "title" }, { "offsetInBeginSection": 441, "offsetInEndSection": 685, "text": "Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 845, "text": "Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.
Results: Our results indicate that, in addition to some fundamental biological functions, the UCSs play an important role in the adaptation of Saccharomyces cerevisiae to the acidic environment, which is backed up by the previous observation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028909", "endSection": "abstract" } ] }, { "body": "Which disease can be classified with the Awaji Criteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28444090", "http://www.ncbi.nlm.nih.gov/pubmed/20659815", "http://www.ncbi.nlm.nih.gov/pubmed/20928911", "http://www.ncbi.nlm.nih.gov/pubmed/27212114", "http://www.ncbi.nlm.nih.gov/pubmed/25843898", "http://www.ncbi.nlm.nih.gov/pubmed/24575803", "http://www.ncbi.nlm.nih.gov/pubmed/21940619", "http://www.ncbi.nlm.nih.gov/pubmed/25597926", "http://www.ncbi.nlm.nih.gov/pubmed/28249004", "http://www.ncbi.nlm.nih.gov/pubmed/28631957", "http://www.ncbi.nlm.nih.gov/pubmed/24239347", "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "http://www.ncbi.nlm.nih.gov/pubmed/21215419", "http://www.ncbi.nlm.nih.gov/pubmed/29742797", "http://www.ncbi.nlm.nih.gov/pubmed/21764635", "http://www.ncbi.nlm.nih.gov/pubmed/22277500", "http://www.ncbi.nlm.nih.gov/pubmed/22246871", "http://www.ncbi.nlm.nih.gov/pubmed/26821620", "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "http://www.ncbi.nlm.nih.gov/pubmed/28457490", "http://www.ncbi.nlm.nih.gov/pubmed/27117334", "http://www.ncbi.nlm.nih.gov/pubmed/23261262", "http://www.ncbi.nlm.nih.gov/pubmed/24698287", "http://www.ncbi.nlm.nih.gov/pubmed/21437935", "http://www.ncbi.nlm.nih.gov/pubmed/23407618", "http://www.ncbi.nlm.nih.gov/pubmed/27440148" ], "ideal_answer": [ "Awaji Criteria are used for amyotrophic lateral sclerosis." ], "exact_answer": [ "amyotrophic lateral sclerosis" ], "type": "factoid", "id": "5c61d278e842deac67000005", "snippets": [ { "offsetInBeginSection": 626, "offsetInEndSection": 876, "text": "Adoption of the Awaji criteria significantly increased the yield of EMG-positive segments in the cervical (P\u2009<\u20090.0005) and lumbosacral (P\u2009<\u20090.0001) regions, and upgraded 19 patients into the probable category and 1 patient into the definite category.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29742797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The Awaji criteria increases the diagnostic sensitivity of the revised El Escorial criteria for amyotrophic lateral sclerosis diagnosis in a Chinese population.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28249004", "endSection": "title" }, { "offsetInBeginSection": 144, "offsetInEndSection": 501, "text": "However, previous studies that have assessed the diagnostic sensitivities of the Awaji criteria (AC) and the revised El Escorial criteria (rEEC) in patients with ALS have been inconsistent, most of them were consensual regarding the advantage of Awaji over conventional criteria. Our study sought to compare the roles of AC and rEEC in the diagnosis of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28249004", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1319, "text": "CONCLUSIONS: Our data demonstrated that the AC exhibited greater diagnostic sensitivity than the rEEC in a Chinese ALS population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28249004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "OBJECTIVE: To assess the added prognostic value of the aggregated clinical and electrodiagnostic data, which define a given diagnostic category according to the Awaji or revised El Escorial criteria at time of diagnosis in patients with amyotrophic lateral sclerosis (ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28631957", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 1033, "text": "Diagnostic category according to Awaji (p\u2009<\u20090.0001) or to revised El Escorial (p\u2009=\u20090.0177) criteria, definite ALS according to Awaji (p\u2009<\u20090.0001) or to revised El Escorial (p\u2009=\u20090.0343) and number of regions with LMN involvement (p\u2009<\u20090.0001) were all associated with shorter survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28631957", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 319, "text": "Methods: This is a cross-sectional and descriptive study including a consecutive series of patients with sporadic amyotrophic lateral sclerosis according to Awaji's criteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28444090", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1120, "text": "The importance of fasciculation potentials in the diagnosis of ALS led to changes in electrophysiological criteria at Awaji consensus conference. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28457490", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1257, "text": "Application of Awaji criteria led to a 23% (95% CI, 12% to 33%; I2=84%) increase in the proportion of patients classified as having probable/definite ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "OBJECTIVE\nTo estimate the potential diagnostic added value of the Awaji criteria for diagnosis of a myotrophiclateral sclerosis (ALS), which have been compared with the previously accepted gold standard the revised El Escorial criteria in several studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 491, "text": "STUDY SELECTION\nWe searched for studies testing the diagnostic accuracy of the Awaji criteria vs the revised El Escorial criteria in patients referred with suspected ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 1643, "offsetInEndSection": 1767, "text": "CONCLUSION\nThe Awaji criteria have a significant clinical impact allowing earlier diagnosis and clinical trial entry in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 851, "text": "In 2006, the Awaji criteria for the diagnosis of ALS were proposed, adding two major points to the diagnostic criteria: electromyography is considered equivalent to clinical examination for the identification of LMN signs and fasciculation potentials resume their prominent place in the diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261262", "endSection": "abstract" }, { "offsetInBeginSection": 1505, "offsetInEndSection": 1690, "text": "CLASSIFICATION OF EVIDENCE\nThis study provides Class IV evidence that the Awaji criteria have a higher sensitivity and the same specificity as the rEEC in identifying patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "OBJECTIVE To estimate the potential diagnostic added value of the Awaji criteria for diagnosis of a myotrophiclateral sclerosis (ALS), which have been compared with the previously accepted gold standard the revised El Escorial criteria in several studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 1505, "offsetInEndSection": 1690, "text": "CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that the Awaji criteria have a higher sensitivity and the same specificity as the rEEC in identifying patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "OBJECTIVE To assess the sensitivity and specificity of the Awaji and revised El Escorial diagnostic criteria (rEEC) in amyotrophic lateral sclerosis (ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "The Awaji Commission recently proposed a modification of the electrodiagnostic criteria for ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "INTRODUCTION Recently, some authors have claimed that the Awaji criteria (AC) are not always more sensitive than the revised El Escorial criteria (rEEC) in amyotrophic lateral sclerosis (ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25597926", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1257, "text": "The updated Awaji criteria enhanced the diagnostic sensitivity in limb-onset ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27212114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "BACKGROUND Recently, new electrophysiological ALS criteria incorporating fasciculation potentials (FPs) as evidence for lower motor neuron signs (Awaji Criteria (AC)) was proposed to provide earlier detection of early-stage ALS than revised El Escorial electrophysiological criteria (REEC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21215419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "The Awaji criteria, recently introduced to increase diagnosis sensitivity in amyotrophic lateral sclerosis (ALS), equate the diagnostic significance of neurogenic electrophysiological changes to clinical signs of lower motor neuron dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24575803", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 827, "text": "Participants had definite, probable, or possible ALS, as defined by the Awaji criteria; or pure motor disorder with clinical features of upper and lower motor neuron dysfunction in at least one body region, progressing over a 6 month follow-up period; or muscle wasting and weakness for at least 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25843898", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 435, "text": "New diagnostic criteria for ALS, the Awaji algorithm, reintroduced fasciculations as evidence of acute denervation equivalent to that of fibrillations and positive sharp waves.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21940619", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 670, "text": "Given that cortical hyperexcitability appears to be an early feature in ALS, the present study assessed the diagnostic utility of a threshold tracking transcranial magnetic stimulation technique as an aid to the research-based Awaji criteria in establishing an earlier diagnosis of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24698287", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1065, "text": "The specificity of the both criteria were identical, 99.5%, indicating the number needed to test in order to diagnose one extra case of ALS was 1.8 (1.5-2) for Awaji criteria and 2.4 (2-2.6) for rEEC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440148", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 381, "text": "We assessed whether the Awaji recommendations improve the sensitivity of the early diagnosis of ALS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 607, "text": "Our retrospective analysis of patients referred over a 6-month period to the electromyography (EMG) laboratory for suspected motor neuron disease (MND) showed a higher agreement of the Awaji modifications than the Airlie House criteria with the clinical diagnosis of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20928911", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1083, "text": "Participants had definite, probable, or possible ALS, as defined by the Awaji criteria; or pure motor disorder with clinical features of upper and lower motor neuron dysfunction in at least one body region, progressing over a 6 month follow-up period; or muscle wasting and weakness for at least 6 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25843898", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1166, "text": "Of the 14 patients diagnosed with probable laboratory-supported ALS, eight switched to probable ALS and six to possible ALS using the Awaji recommendations; none of the patients with an ALS mimic was diagnosed with ALS according to the Awaji recommendations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 622, "text": "OBJECTIVE: To estimate the potential diagnostic added value of the Awaji criteria for diagnosis of a myotrophiclateral sclerosis (ALS), which have been compared with the previously accepted gold standard the revised El Escorial criteria in several studies.
DATA SOURCES: MEDLINE and Web of Science (until October2011).
STUDY SELECTION: We searched for studies testing the diagnostic accuracy of the Awaji criteria vs the revised El Escorial criteria in patients referred with suspected ALS.
DATA EXTRACTION: Evaluation and data extraction of identified studies were done independently.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1301, "text": "Application of Awaji criteria led to a 23% (95% CI, 12% to 33%; I2=84%) increase in the proportion of patients classified as having probable/definite ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1824, "text": "Diagnostic accuracy of Awaji criteria was higher in bulbar- than in limb-onset cases.
CONCLUSION: The Awaji criteria have a significant clinical impact allowing earlier diagnosis and clinical trial entry in ALS.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892641", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 197, "text": "We assessed whether the Awaji recommendations improve the sensitivity of the early diagnosis of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 542, "text": "Using the El Escorial criteria, 51 patients were diagnosed with definite or probable ALS, 14 with probable laboratory-supported ALS, and 28 with possible ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 723, "text": "Applying the Awaji recommendations, 66 patients were diagnosed with either definite or probable ALS, and 27 with possible ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 982, "text": "Of the 14 patients diagnosed with probable laboratory-supported ALS, eight switched to probable ALS and six to possible ALS using the Awaji recommendations; none of the patients with an ALS mimic was diagnosed with ALS according to the Awaji recommendations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20536375", "endSection": "abstract" } ] }, { "body": "Endolymphatic hydrops is associated with Meniere\u2019s disease. Please provide a summary of endoymphatic hydrops including the symptoms and affected body part.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27999985", "http://www.ncbi.nlm.nih.gov/pubmed/27564645", "http://www.ncbi.nlm.nih.gov/pubmed/30503567", "http://www.ncbi.nlm.nih.gov/pubmed/27942898" ], "ideal_answer": [ "Endolymphatic hydrops is a disorder of the inner ear. It consists of an excessive build-up of the endolymph fluid, which fills the hearing and balance structures of the inner ear. The symptoms of endolymphatic hydrops include the feeling of pressure or fullness in the ears, hearing loss, tinnitus (ringing in the ears) and balance problems." ], "type": "summary", "id": "5c530ff67e3cb0e23100000f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 661, "text": "Endolymphatic hydrops (EH) can be studied in patients by MRI. With the semi-quantitative grading system, previous imaging studies showed discrepancies in the occurrence and grading of EH in patients with Meniere's disease (MD). Here, we compared the inversion of the saccule to utricle area ratio (SURI) with the semi-quantitative method of grading conventionally used to diagnose MD.METHODS: Imaging was carried out on a 3-T MRI scanner. We performed 3D-FLAIR sequences 4\u00a0h after a single intravenous dose of contrast agent. Two radiologists independently studied the morphology of the inner ear structures in the healthy subjects and MD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27999985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "M\u00e9ni\u00e8re's disease is associated with hydrops of the inner ear endolymphatic space, and histopathologically, the cochlea and vestibule are usually involved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27942898", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 120, "text": "All definite Meniere's disease (MD) had endolymphatic hydrops (EH) at least in the cochlea or the vestibule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27564645", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 329, "text": "To employ magnetic resonance imaging (MRI) to measure the volume of the inner ear endolymphatic space (ELS) in patients with acute low-tone sensorineural hearing loss (ALHL), sudden deafness (SD), cochlear Meniere's disease (cMD), and unilateral MD (uMD) compared with control subjects (CS) with chronic rhinosinusitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30503567", "endSection": "abstract" } ] }, { "body": "Where does gemtuzumab ozogamicin bind?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29476018" ], "ideal_answer": [ "Gemtuzumab ozogamicin binds to CD33" ], "exact_answer": [ "CD33" ], "type": "factoid", "id": "5c6473b2e842deac6700001b", "snippets": [ { "offsetInBeginSection": 267, "offsetInEndSection": 357, "text": "Gemtuzumab ozogamicin is a CD33-targeted antibody-drug conjugate joined to calicheamicin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29476018", "endSection": "abstract" } ] }, { "body": "Where, in what US state, was there a measles outbreak in an Amish community", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28302434", "http://www.ncbi.nlm.nih.gov/pubmed/26103154", "http://www.ncbi.nlm.nih.gov/pubmed/27705270" ], "ideal_answer": [ "The measles outbreak started an Amish community in Ohio" ], "exact_answer": [ "Ohio" ], "type": "factoid", "id": "5c5312097e3cb0e231000011", "snippets": [ { "offsetInBeginSection": 395, "offsetInEndSection": 474, "text": "Recent outbreaks in Amish communities include a 2014 measles outbreak in Ohio, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28302434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Measles outbreaks in the United States continue to occur in subpopulations with sufficient numbers of undervaccinated individuals, with a 2014 outbreak in Amish communities in Ohio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26103154", "endSection": "abstract" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1874, "text": "CONCLUSIONS\nThe key epidemiologic features of a measles outbreak in the Amish community in Ohio were transmission primarily within households, the small proportion of Amish people affected, and the large number of people in the Amish community who sought vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27705270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Measles outbreaks in the United States continue to occur in subpopulations with sufficient numbers of undervaccinated individuals, with a 2014 outbreak in Amish communities in Ohio pushing the annual cases to the highest national number reported in the last 20 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26103154", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 505, "text": "Recent outbreaks in Amish communities include a 2014 measles outbreak in Ohio, resulting in 368 cases reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28302434", "endSection": "abstract" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1874, "text": "CONCLUSIONS The key epidemiologic features of a measles outbreak in the Amish community in Ohio were transmission primarily within households, the small proportion of Amish people affected, and the large number of people in the Amish community who sought vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27705270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Modeling Measles Transmission in the North American Amish and Options for Outbreak Response.Measles outbreaks in the United States continue to occur in subpopulations with sufficient numbers of undervaccinated individuals, with a 2014 outbreak in Amish communities in Ohio pushing the annual cases to the highest national number reported in the last 20 years. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26103154", "endSection": "title" } ] }, { "body": "Is there any role for HUWE1 in MYC signalling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28003334" ], "ideal_answer": [ "Yes. HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation." ], "exact_answer": "yes", "type": "yesno", "id": "5c640c2ee842deac67000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28003334", "endSection": "title" }, { "offsetInBeginSection": 397, "offsetInEndSection": 1340, "text": "To determine the importance of HUWE1, we chose to examine its function in colorectal cancer, where it is mutated in up to 15 per cent of tumours. Modelling of identified mutations showed that they inactivate the E3 ubiquitin ligase activity of HUWE1. Genetic deletion of Huwe1 rapidly accelerated tumourigenic in mice carrying loss of the intestinal tumour suppressor gene Apc, with a dramatic increase in tumour initiation. Mechanistically, this phenotype was driven by increased MYC and rapid DNA damage accumulation leading to loss of the second copy of Apc The increased levels of DNA damage sensitised Huwe1-deficient tumours to DNA-damaging agents and to deletion of the anti-apoptotic protein MCL1. Taken together, these data identify HUWE1 as a bona fide tumour suppressor gene in the intestinal epithelium and suggest a potential vulnerability of HUWE1-mutated tumours to DNA-damaging agents and inhibitors of anti-apoptotic proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28003334", "endSection": "abstract" } ] }, { "body": "List MHC-I-associated inflammatory disorders.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27522479", "http://www.ncbi.nlm.nih.gov/pubmed/25892735" ], "ideal_answer": [ "ankylosing spondylitis\nbirdshot chorioretinopathy\nBeh\u00e7et's disease \npsoriasis" ], "exact_answer": [ [ "ankylosing spondylitis" ], [ "birdshot chorioretinopathy" ], [ "Beh\u00e7et's disease" ], [ "psoriasis" ] ], "type": "list", "id": "5c76c1457c78d694710000a6", "snippets": [ { "offsetInBeginSection": 258, "offsetInEndSection": 423, "text": "This review will focus on the four major MHC-I-associated inflammatory disorders: ankylosing spondylitis, birdshot chorioretinopathy, Beh\u00e7et's disease and psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27522479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Birdshot chorioretinopathy is a rare ocular inflammation whose genetic association with HLA-A*29:02 is the highest between a disease and a major histocompatibility complex (MHC) molecule. It belongs to a group of MHC-I-associated inflammatory disorders, also including ankylosing spondylitis, psoriasis, and Beh\u00e7et's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25892735", "endSection": "abstract" } ] }, { "body": "What is the predicted function for TMEM132 family?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29088312" ], "ideal_answer": [ "The TMEM132 family proteins are strongly predicted to have a cellular adhesion function, connecting the extracellular medium with the intracellular actin cytoskeleton." ], "exact_answer": [ "Cellular adhesion function" ], "type": "factoid", "id": "5c65abd17c78d69471000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "TMEM132: an ancient architecture of cohesin and immunoglobulin domains define a new family of neural adhesion molecules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 868, "text": "Here we show the full domain architecture of human TMEM132 family proteins solved using in-depth sequence and structural analysis. We reveal them to be five previously unappreciated cell adhesion molecules whose domain architecture has an early holozoan origin prior to the emergence of choanoflagellates and metazoa. The extra-cellular portions of TMEM132 proteins contain five conserved domains including three tandem immunoglobulin domains, and a cohesin domain homologue, the first such domain found in animals. These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 867, "text": "These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1009, "text": "These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 1029, "text": "These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton.
Contact: luis.sanchez-pulido@igmm.ed.ac.uk.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088312", "endSection": "abstract" } ] }, { "body": "What type of topoisomerase inhibitor is gepotidacin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27161642" ], "ideal_answer": [ "Gepotidacin is a type IIA topoisomerase inhibitor." ], "exact_answer": [ "type IIA" ], "type": "factoid", "id": "5c0115e0133db5eb78000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Gepotidacin, a novel triazaacenaphthylene antibacterial agent, is the first in a new class of type IIA topoisomerase inhibitors with activity against many biothreat and conventional pathogens, including Neisseria gonorrhoeae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27161642", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Alpelisib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27126994", "http://www.ncbi.nlm.nih.gov/pubmed/26793003", "http://www.ncbi.nlm.nih.gov/pubmed/30167089", "http://www.ncbi.nlm.nih.gov/pubmed/29401002", "http://www.ncbi.nlm.nih.gov/pubmed/29850984", "http://www.ncbi.nlm.nih.gov/pubmed/28852212", "http://www.ncbi.nlm.nih.gov/pubmed/29453241", "http://www.ncbi.nlm.nih.gov/pubmed/29563327", "http://www.ncbi.nlm.nih.gov/pubmed/29284706", "http://www.ncbi.nlm.nih.gov/pubmed/28363909", "http://www.ncbi.nlm.nih.gov/pubmed/29789630" ], "ideal_answer": [ "Alpelisib is selective inhibitor of Phosphatidylinositol 3-Kinase \u03b1 (PI3K\u03b1). It is used for treatment of cancer." ], "type": "summary", "id": "5c6633f27c78d69471000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "The PI3K\u03b1 Inhibitor Alpelisib Has Activity in", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29453241", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The PI3K\u03b1 inhibitor alpelisib achieved a 58.2% disease control rate in PIK3CA-altered solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29453241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Purpose: We describe herein a novel P447_L455 deletion in the C2 domain of PIK3CA in a patient with an ER+ breast cancer with an excellent response to the PI3K\u03b1 inhibitor alpelisib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29284706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Phosphatidylinositol 3-Kinase \u03b1-Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29401002", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Purpose We report the first-in-human phase Ia study to our knowledge ( ClinicalTrials.gov identifier: NCT01219699) identifying the maximum tolerated dose and assessing safety and preliminary efficacy of single-agent alpelisib (BYL719), an oral phosphatidylinositol 3-kinase \u03b1 (PI3K\u03b1)-selective inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29401002", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 751, "text": "Here, we have determined the effects of new anticancer drugs targeting specific PI3K isoforms on INaL and action potentials (APs) in mouse cardiomyocytes and Chinese hamster ovary cells (CHO). Chronic exposure (10-100 nM; 5-48 hours) to PI3K-\u03b1-specific subunit inhibitors BYL710 (alpelisib) and A66 and a pan-PI3K inhibitor (BKM120) increased INaL in SCN5A-transfected CHO cells and mouse cardiomyocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29563327", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1057, "text": "Combining ribociclib with the alpha-specific PI3K inhibitor alpelisib showed a synergistic effect in two NPC PDX models in nude mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29789630", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 296, "text": "his study aimed to assess the safety and activity of alpelisib (a PI3K\u03b1 isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850984", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 295, "text": "This study aimed to assess the safety and activity of alpelisib (a PI3K\u03b1 isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "PURPOSE\nAlpelisib, a selective oral inhibitor of the class I PI3K catalytic subunit p110\u03b1, has shown synergistic antitumor activity with endocrine therapy against ER+/PIK3CA-mutated breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27126994", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 427, "text": "We explored whether PI3K inhibitors, buparlisib and alpelisib, enhance the efficacy of tamoxifen against ER-positive BC cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852212", "endSection": "abstract" }, { "offsetInBeginSection": 61, "offsetInEndSection": 289, "text": "PI3K inhibitors, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3K\u03b1-selective inhibitor alpelisib (BYL719), currently in clinical development by Novartis Oncology, may therefore be effective as anticancer agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26793003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "PURPOSE Alpelisib, a selective oral inhibitor of the class I PI3K catalytic subunit p110\u03b1, has shown synergistic antitumor activity with endocrine therapy against ER+/PIK3CA-mutated breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27126994", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 435, "text": "Patients with refractory BRAFV600-mutant metastatic CRC (mCRC) were treated with a selective RAF kinase inhibitor (encorafenib) plus a monoclonal antibody targeting EGFR (cetuximab), with (n = 28) or without (n = 26) a PI3K\u03b1 inhibitor (alpelisib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28363909", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1056, "text": "Combining ribociclib with the alpha-specific PI3K inhibitor alpelisib showed a synergistic effect in two NPC PDX models in nude mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29789630", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 263, "text": "We assessed the safety and activity of alpelisib, an oral, selective PI3K p110\u03b1 inhibitor, plus paclitaxel in patients with advanced solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30167089", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 472, "text": "This study aimed to assess the safety and activity of alpelisib (a PI3K\u03b1 isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC.
METHODS: Patients with HER2-positive MBC that had progressed on trastuzumab-based therapy were treated with alpelisib daily and T-DM1 3.6\u00a0mg/kg every 3 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850984", "endSection": "abstract" } ] }, { "body": "What is the normal function p53?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28749203", "http://www.ncbi.nlm.nih.gov/pubmed/28937686", "http://www.ncbi.nlm.nih.gov/pubmed/28984872", "http://www.ncbi.nlm.nih.gov/pubmed/29242642" ], "ideal_answer": [ "Wild-type p53 can suppress tumour development by multiple pathways." ], "exact_answer": [ "tumor suppressor" ], "type": "factoid", "id": "5c5f1f371a4c55d80b00001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28984872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The tumor suppressor p53 is a key regulator of apoptosis induced by various cellular stresses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28937686", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 256, "text": "Direct functional restoration of p53 as a transcription factor has been difficult to achieve in the clinic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28749203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "The tumour suppressor gene TP53 is the most frequently mutated gene in cancer. Wild-type p53 can suppress tumour development by multiple pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29242642", "endSection": "abstract" } ] }, { "body": "What is eravacycline?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25808831" ], "ideal_answer": [ "Finafloxacin is a fluoroquinolone antimicrobial agent that exhibits optimum efficacy in slightly acidic environments. It is being developed to treat serious bacterial infections associated with an acidic environment, including urinary tract infections, complicated urinary tract infections, pyelonephritis and Helicobacter pylori infections, while it has already received approval for the treatment of acute otitis externa." ], "type": "summary", "id": "5c011bbf133db5eb7800002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 807, "text": "Finafloxacin is a fluoroquinolone antimicrobial agent that exhibits optimum efficacy in slightly acidic environments. It is being developed by MerLion Pharmaceuticals to treat serious bacterial infections associated with an acidic environment, including urinary tract infections and Helicobacter pylori infections. An otic suspension of finafloxacin (Xtoro\u2122), developed by Alcon (a division of Novartis), was recently approved in the USA for the treatment of acute otitis externa, and a Common Technical Document for this indication was also filed in Canada. Oral and/or intravenous formulations are in phase I and II evaluation in uncomplicated urinary tract infections (Germany and Singapore), complicated urinary tract infections and pyelonephritis (Germany and Poland) and H. pylori infection (Germany).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25808831", "endSection": "abstract" } ] }, { "body": "What is PEGylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26523632" ], "ideal_answer": [ "Attachment of a chain of poly(ethylene glycol) (PEG) to a therapeutic protein, a process widely known as PEGylation, can lead to several beneficial effects. It has the potential to significantly delay aggregation of the protein by steric shielding, a frequently encountered issue in the development of protein drugs. Moreover, it can modify the pharmacokinetic profile of the PEGylated protein by delaying renal excretion, leading to a longer half-life (t1/2) of the drug. By steric hindrance, it can also inhibit interactions between the protein drug and proteases as well as the host immune system, thereby inhibiting inactivation of the PEGylated protein and also attenuating its immunogenicity." ], "type": "summary", "id": "5c66d3977c78d69471000017", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 699, "text": "ttachment of a chain of poly(ethylene glycol) (PEG) to a therapeutic protein, a process widely known as PEGylation, can lead to several beneficial effects. It has the potential to significantly delay aggregation of the protein by steric shielding, a frequently encountered issue in the development of protein drugs. Moreover, it can modify the pharmacokinetic profile of the PEGylated protein by delaying renal excretion, leading to a longer half-life (t1/2) of the drug. By steric hindrance, it can also inhibit interactions between the protein drug and proteases as well as the host immune system, thereby inhibiting inactivation of the PEGylated protein and also attenuating its immunogenicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26523632", "endSection": "abstract" } ] }, { "body": "What is the 3D tomography imaging technique for diagnosis of eye disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25606299", "http://www.ncbi.nlm.nih.gov/pubmed/29111842", "http://www.ncbi.nlm.nih.gov/pubmed/28782513", "http://www.ncbi.nlm.nih.gov/pubmed/20542136", "http://www.ncbi.nlm.nih.gov/pubmed/29396390", "http://www.ncbi.nlm.nih.gov/pubmed/25570836", "http://www.ncbi.nlm.nih.gov/pubmed/28677229" ], "ideal_answer": [ "Currently, eye care professionals use optical coherence tomography (OCT) scans to help diagnose eye conditions." ], "exact_answer": [ "optical coherence tomography." ], "type": "factoid", "id": "5c5249077e3cb0e23100000b", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 171, "text": "To compare the effect of elevated intraocular pressure (IOP) on retinal capillary filling in elderly vs adult rats using optical coherence tomography angiography ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28782513", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 504, "text": "OCT data were captured using an optical microangiography (OMAG) scanning protocol and then post-processed to obtain both structural and vascular images.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28782513", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 96, "text": " Optical coherence tomography is used routinely in management of diabetic eye disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28677229", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 324, "text": "The study aims to evaluate the use of optical coherence tomography combined with a fundus camera compared with a fundus camera only", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28677229", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 193, "text": "To evaluate the ability of new Swept source (SS) optical coherence tomography (OCT) technology to detect changes in retinal and choroidal thickness in patients with Parkinson's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29111842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Retinal and Choroidal Changes in Patients with Parkinson's Disease Detected by Swept-Source Optical Coherence Tomography.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29111842", "endSection": "title" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1763, "text": "New SS technology for OCT devices detects retinal thinning in PD patients, providing increased depth analysis of the choroid in these patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29111842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Diagnostic Function of 3D Optical Coherence Tomography Images in Diagnosis of Vogt-Koyanagi-Harada Disease at Acute Uveitis Stage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29396390", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 251, "text": "This study analyzed the macular 3D-OCT images of Vogt-Koyanagi-Harada disease (VKH) in uveitis, explored the characteristics of 3D-OCT images of the macular region of VKH, and assessed which characteristics contribute most to VKH diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29396390", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 395, "text": "The 3D-OCT examination of 25 cases of VKH was performed on the macular area, and the image characteristics were analyzed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29396390", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1409, "text": "The implications of new image analysis approaches include improved reproducibility of measurements garnered from 3D-OCT, which may then help improve disease discrimination and progression detection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20542136", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 715, "text": "3D spectral domain optical coherence tomography (SD-OCT), an optical imaging technique, has been commonly used to discriminate glaucomatous from healthy subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25606299", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 576, "text": "3D spectral domain optical coherence tomography (SD-OCT), an optical imaging technique, has been commonly used to discriminate glaucomatous from healthy subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25570836", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 819, "text": "In this paper, we present a new framework for detection of glaucoma progression using 3D SD-OCT images.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25606299", "endSection": "abstract" } ] }, { "body": "Which was the first mutant IDH2 inhibitor to be approved for patients with acute myeloid leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30360730" ], "ideal_answer": [ "Enasidenib was the first mutant IDH2 inhibitor to be approved for the treatment of refractory and relapsed acute myeloid leukemia." ], "exact_answer": [ "Enasidenib" ], "type": "factoid", "id": "5c65897a7c78d69471000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360730", "endSection": "title" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1107, "text": "The various findings about enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360730", "endSection": "abstract" }, { "offsetInBeginSection": 1706, "offsetInEndSection": 1907, "text": "Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360730", "endSection": "abstract" } ] }, { "body": "What part of the body is affected by Meniere's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29283101", "http://www.ncbi.nlm.nih.gov/pubmed/28304075", "http://www.ncbi.nlm.nih.gov/pubmed/28760332", "http://www.ncbi.nlm.nih.gov/pubmed/12486835", "http://www.ncbi.nlm.nih.gov/pubmed/21319945" ], "ideal_answer": [ "The inner ear is the body part that is associated with Meniere's disease." ], "exact_answer": [ "inner ear" ], "type": "factoid", "id": "5c5310c37e3cb0e231000010", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 145, "text": "Steroids have been widely used to treat inner-ear diseases such as sudden sensorineural hearing loss, tinnitus, and Meniere's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28304075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Meniere's disease is an inner ear disease, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28760332", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 88, "text": "M\u00e9ni\u00e8re's Disease (MD) is a chronic, non-life threatening inner ear disease, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29283101", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 754, "text": "The utricular duct was blocked in 16 (76%) ears affected by Meniere's disease and 11 (52%) normal ears (p = 0.112).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21319945", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1365, "text": "Meniere's disease is (grossly) equally common in each sex, and right and left ears are affected with fairly equal frequency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12486835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Meniere's disease is a disease of the inner ear characterized by a triad of symptoms: vestibular symptoms, auditory symptoms, and pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12486835", "endSection": "abstract" } ] }, { "body": "Which two drugs are included in the MAVYRET pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28929412", "http://www.ncbi.nlm.nih.gov/pubmed/29089721" ], "ideal_answer": [ "MAVYRET pill includes glecaprevir and pibrentasvir. It is used for treatment of hepatitis C infection." ], "exact_answer": [ [ "glecaprevir" ], [ "pibrentasvir" ] ], "type": "list", "id": "5c6e146a7c78d6947100004c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "A fixed-dose combination tablet of the hepatitis C virus (HCV) NS3/4A protease inhibitor (PI) glecaprevir and the HCV NS5A inhibitor pibrentasvir [glecaprevir/pibrentasvir; MAVIRET\u2122 (EU); MAVYRET\u2122 (USA)] has been developed by AbbVie.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Aminolevulinic acid hydrochloride (Gleolan) for the visualization of malignant tissue during surgery; delafloxacin (Baxdela) for certain acute bacterial skin infections; and glecaprevir/pibrentasvir (Mavyret) for chronic HCV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29089721", "endSection": "abstract" } ] }, { "body": "Describe the 4D-CHAINS algorithm", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29374165" ], "ideal_answer": [ "4D-CHAINS/autoNOE-Rosetta is a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta." ], "type": "summary", "id": "5c60382ac01990ff41000002", "snippets": [ { "offsetInBeginSection": 260, "offsetInEndSection": 1076, "text": "Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta. Our results on four targets ranging in size from 15.5 to 27.3\u2009kDa illustrate that the structures of proteins can be determined accurately and in an unsupervised manner in a matter of days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 753, "text": "The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 400, "text": "Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 498, "text": "Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 851, "text": "The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" } ] }, { "body": "What is an organoid?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30510992", "http://www.ncbi.nlm.nih.gov/pubmed/30324441", "http://www.ncbi.nlm.nih.gov/pubmed/29174804" ], "ideal_answer": [ "Organoids are a three-dimensional in vitro culture platform constructed from self-organizing stem cells. They can almost accurately recapitulate tumor heterogeneity and microenvironment \"in a dish,\" which surpass established cell lines and are not as expensive and time-consuming as PDTXs. As an intermediate model, tumor organoids are also used to study the fundamental issues of tumorigenesis and metastasis. They are specifically applied for drug testing and stored as \"living biobanks.\"" ], "type": "summary", "id": "5c780caf7c78d694710000af", "snippets": [ { "offsetInBeginSection": 169, "offsetInEndSection": 661, "text": ". Organoids are a three-dimensional in\u00a0vitro culture platform constructed from self-organizing stem cells. They can almost accurately recapitulate tumor heterogeneity and microenvironment \"in a dish,\" which surpass established cell lines and are not as expensive and time-consuming as PDTXs. As an intermediate model, tumor organoids are also used to study the fundamental issues of tumorigenesis and metastasis. They are specifically applied for drug testing and stored as \"living biobanks.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29174804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 421, "text": "The introduction of stem cell-based technologies for the derivation of three-dimensional retinal tissues, the so-called retinal organoids, offers many new possibilities for vision research: Organoids facilitate studies on retinal development and in vitro retinal disease modeling, as well as being valuable for drug testing. Further, retinal organoids also provide an unlimited cell source for cell replacement therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30324441", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1711, "text": "The single cell-based 3D organoid system may\u00a0serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30510992", "endSection": "abstract" } ] }, { "body": "Do raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 Diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29202274" ], "ideal_answer": [ "yes, raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 Diabetes." ], "exact_answer": "yes", "type": "yesno", "id": "5c674aed7c78d69471000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "The NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a critical role in insulin resistance and the pathogenesis of type 2 diabetes. Red raspberry (RB) contains high amounts of dietary fibers and polyphenolic compounds, which are known for their anti-oxidative and anti-inflammatory effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29202274", "endSection": "abstract" } ] }, { "body": "Are Mesenchymal stem cells (MSC) multipotent cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19886822", "http://www.ncbi.nlm.nih.gov/pubmed/27102896" ], "ideal_answer": [ "Yes, Mesenchymal stem cells (MSC) are multipotent cells." ], "exact_answer": "yes", "type": "yesno", "id": "5c7836dad774d04240000002", "snippets": [ { "offsetInBeginSection": 106, "offsetInEndSection": 160, "text": "multipotent mesenchymal bone marrow-derived stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27102896", "endSection": "title" }, { "offsetInBeginSection": 868, "offsetInEndSection": 916, "text": "multipotent hESC-derived mesenchymal cells (MCs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19886822", "endSection": "abstract" } ] }, { "body": "Which two drugs are included in the Entresto pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30084228", "http://www.ncbi.nlm.nih.gov/pubmed/27697814", "http://www.ncbi.nlm.nih.gov/pubmed/28944989", "http://www.ncbi.nlm.nih.gov/pubmed/28676030", "http://www.ncbi.nlm.nih.gov/pubmed/26976916", "http://www.ncbi.nlm.nih.gov/pubmed/27284124", "http://www.ncbi.nlm.nih.gov/pubmed/26975167", "http://www.ncbi.nlm.nih.gov/pubmed/29532764", "http://www.ncbi.nlm.nih.gov/pubmed/29375230", "http://www.ncbi.nlm.nih.gov/pubmed/30276760", "http://www.ncbi.nlm.nih.gov/pubmed/29469206", "http://www.ncbi.nlm.nih.gov/pubmed/26417173", "http://www.ncbi.nlm.nih.gov/pubmed/29352367", "http://www.ncbi.nlm.nih.gov/pubmed/28824789", "http://www.ncbi.nlm.nih.gov/pubmed/26466333", "http://www.ncbi.nlm.nih.gov/pubmed/28883863", "http://www.ncbi.nlm.nih.gov/pubmed/29398176", "http://www.ncbi.nlm.nih.gov/pubmed/27804100" ], "ideal_answer": [ "Entresto includes Sacubitril and Valsartan." ], "exact_answer": [ [ "Sacubitril" ], [ "Valsartan" ] ], "type": "list", "id": "5c61bd04e842deac67000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "A novel antihypertensive drug, LCZ696 (Entresto\u00ae), has recently been introduced, which combines the action of an antagonist of the renin-angiotensin-aldosterone system (RAAS), effectively decreasing the blood pressure, with an inhibition of neprilysin, which is responsible for metabolizing natriuretic peptides exerting antihypertensive and antifibrotic effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944989", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 1266, "text": "METHODS AND RESULTS: The ENTRESTO-SAS trial is a 3-month, multicentric, prospective, open-label real-life cohort study. Patients eligible for sacubitril-valsartan treatment (i.e. adults with left ventricular ejection fraction \u226435%, who remain symptomatic despite optimal treatment with an angiotensin-converting enzyme inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist) will be evaluated before and after 3\u00a0months of treatment (nocturnal ventilatory polygraphy, echocardiography, laboratory testing, and quality-of-life and SDB questionnaires). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29469206", "endSection": "abstract" }, { "offsetInBeginSection": 1640, "offsetInEndSection": 1765, "text": " We sought to assess in the ENTRESTO-SAS trial whether sacubitril-valsartan could improve the outcome of SDB in CHF patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29469206", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 727, "text": "This positive change in regulatory perspective coupled with successful commercialization of valsartan-sacubitril co-crystal (Entresto, Novartis) has now brought co-crystals into focus, in both industries as well as academia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29352367", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 321, "text": "We present a case of a 61-year-old man with ischemic cardiomyopathy receiving sacubitril/valsartan (Entresto; Novartis, Cambridge, MA) who developed profound hypotension after HT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29398176", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 602, "text": "Recently, the Food and Drug Administration (FDA) approved a drug with brand name Entresto (Sacubitril/Valsartan or LCZ696), an angiotensin receptor neprilysin inhibitor for the use in Heart Failure with Reduced Ejection Fraction (HFrEF) patients instead of ACEI's and ARBs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29532764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "A prospective, randomized, double-blind, placebo-controlled pilot study of sacubitril/valsartan (Entresto) in dogs with cardiomegaly secondary to myxomatous mitral valve disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30084228", "endSection": "title" }, { "offsetInBeginSection": 248, "offsetInEndSection": 440, "text": "This review of the literature highlights the new generation of HF drug, sacubitril-valsartan (SV), trade name Entresto (researched as LCZ696, Novartis) which simultaneously blocks RAAS and NP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28824789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "\u25bc Sacubitril valsartan (Entresto-Novartis) is a new oral drug licensed for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27284124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Sacubitril/valsartan (Entresto) for chronic heart failure; brexpiprazole (Rexulti) for major depressive disorder and schizophrenia; and lumacaftor/ivacaftor (Orkambi) for cystic fibrosis involving specific CFTR mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26417173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Correction to: Do Limitations in the Design of PARADIGM-HF Justify the Slow Real World Uptake of Sacubitril/Valsartan (Entresto)?The original version of this article unfortunately contained a mistake. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30276760", "endSection": "title" } ] }, { "body": "Is there a deep-learning algorithm for protein solubility prediction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29554211" ], "ideal_answer": [ "Yes. DeepSol is a novel deep learning-based protein solubility predictor. It is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence." ], "exact_answer": "yes", "type": "yesno", "id": "5c6b198f7c78d69471000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "DeepSol: a deep learning framework for sequence-based protein solubility prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554211", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 618, "text": "Protein solubility plays a vital role in pharmaceutical research and production yield. For a given protein, the extent of its solubility can represent the quality of its function, and is ultimately defined by its sequence. Thus, it is imperative to develop novel, highly accurate in silico sequence-based protein solubility predictors. In this work we propose, DeepSol, a novel Deep Learning-based protein solubility predictor. The backbone of our framework is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "DeepSol: a deep learning framework for sequence-based protein solubility prediction.Protein solubility plays a vital role in pharmaceutical research and production yield. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554211", "endSection": "title" } ] }, { "body": "Have machine learning methods been used to predict the severity of major depressive disorder(MDD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26821982", "http://www.ncbi.nlm.nih.gov/pubmed/29879133", "http://www.ncbi.nlm.nih.gov/pubmed/25066141", "http://www.ncbi.nlm.nih.gov/pubmed/30286415", "http://www.ncbi.nlm.nih.gov/pubmed/27551669", "http://www.ncbi.nlm.nih.gov/pubmed/28702811", "http://www.ncbi.nlm.nih.gov/pubmed/26728563", "http://www.ncbi.nlm.nih.gov/pubmed/22544901", "http://www.ncbi.nlm.nih.gov/pubmed/29682732" ], "ideal_answer": [ "Machine-learning (ML) models developed from self-reports can be used to predict persistence and severity of major depressive disorder(MDD)" ], "exact_answer": "yes", "type": "yesno", "id": "5c5215e67e3cb0e231000004", "snippets": [ { "offsetInBeginSection": 300, "offsetInEndSection": 484, "text": "Here, we conduct a meta-review to identify predictors of response to antidepressant therapy in order to select robust input features for machine learning models of treatment response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286415", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 117, "text": "machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28702811", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29879133", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 132, "text": "persistence and severity of major depressive disorder from baseline self-reports", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26728563", "endSection": "title" }, { "offsetInBeginSection": 1572, "offsetInEndSection": 1778, "text": " These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26728563", "endSection": "abstract" }, { "offsetInBeginSection": 2017, "offsetInEndSection": 2189, "text": "Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544901", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1813, "text": "Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "BACKGROUND\nAlthough variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "BACKGROUND Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27551669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "OBJECTIVE We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26821982", "endSection": "abstract" }, { "offsetInBeginSection": 2145, "offsetInEndSection": 2317, "text": "Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "BACKGROUND: Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25066141", "endSection": "abstract" } ] }, { "body": "What is known about the gut bacteria and depression.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28215162", "http://www.ncbi.nlm.nih.gov/pubmed/29432299", "http://www.ncbi.nlm.nih.gov/pubmed/28455694", "http://www.ncbi.nlm.nih.gov/pubmed/29134359" ], "ideal_answer": [ "Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways.\n\nMajor depressive disorder (MDD) is a highly prevalent and debilitating mental illness, which is associated with disorder of gut microbiota." ], "type": "summary", "id": "5c5f2d5a1a4c55d80b000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS)\u00a0pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28455694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Comparative metaproteomics analysis shows altered fecal microbiota signatures in patients with major depressive disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432299", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Major depressive disorder (MDD) is a highly prevalent and debilitating mental illness, which is associated with disorder of gut microbiota. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432299", "endSection": "abstract" } ] }, { "body": "Can midostaurin inhibit angiogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29487059" ], "ideal_answer": [ "Yes, midostaurin can inhibit angiogenesis through the inhibition of ithe vascular endothelial growth factor receptor." ], "exact_answer": "yes", "type": "yesno", "id": "5c6583117c78d69471000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Midostaurin was a prototype kinase inhibitor, originally developed as a protein kinase C inhibitor and subsequently as an angiogenesis inhibitor, based on its inhibition of vascular endothelial growth factor receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29487059", "endSection": "abstract" } ] }, { "body": "For which indications has midostaurin received FDA and EMA approval?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30069632" ], "ideal_answer": [ "Midostaurin was approved by the Food and Drug Administration (FDA) and the European Medical Agency (EMA) for acute myeloid leukemia with activating FLT3 mutations in combination with intensive induction and consolidation therapy as well as aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia (MCL)." ], "exact_answer": [ [ "Acute myeloid leukemia with activating FLT3 mutations" ], [ "Aggressive systemic mastocytosis" ], [ "Systemic mastocytosis with associated hematological neoplasm" ], [ "Mast cell leukemia" ] ], "type": "list", "id": "5c6585287c78d69471000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Midostaurin: A Multiple Tyrosine Kinases Inhibitor in Acute Myeloid Leukemia and Systemic Mastocytosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30069632", "endSection": "title" }, { "offsetInBeginSection": 283, "offsetInEndSection": 661, "text": "Midostaurin was approved by the Food and Drug Administration (FDA) and the European Medical Agency (EMA) for acute myeloid leukemia with activating FLT3 mutations in combination with intensive induction and consolidation therapy as well as aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia (MCL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30069632", "endSection": "abstract" } ] }, { "body": "Does Groucho related gene 5 (GRG5) have a role only in late development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30214018" ], "ideal_answer": [ "Groucho related gene 5 (GRG5) has been described as a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. By both loss and gain of function approaches ablation of GRG5 has been shown to deregulate the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential." ], "exact_answer": "no", "type": "yesno", "id": "5c629fffe842deac67000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 638, "text": "Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30214018", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 271, "text": "Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30214018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions.Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30214018", "endSection": "title" } ] }, { "body": "Which drugs are included in the Orkambi pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28667089", "http://www.ncbi.nlm.nih.gov/pubmed/28891346", "http://www.ncbi.nlm.nih.gov/pubmed/27804127", "http://www.ncbi.nlm.nih.gov/pubmed/29351449", "http://www.ncbi.nlm.nih.gov/pubmed/26417173", "http://www.ncbi.nlm.nih.gov/pubmed/27990075", "http://www.ncbi.nlm.nih.gov/pubmed/29903751", "http://www.ncbi.nlm.nih.gov/pubmed/29146575", "http://www.ncbi.nlm.nih.gov/pubmed/27792891", "http://www.ncbi.nlm.nih.gov/pubmed/28611092", "http://www.ncbi.nlm.nih.gov/pubmed/28769592" ], "ideal_answer": [ "Orkambi pill includes lumacaftor combined with ivacaftor. It is approved for treatment of cystic fibrosis with F508del-CFTR mutation." ], "exact_answer": [ [ "lumacaftor" ], [ "ivacaftor" ] ], "type": "list", "id": "5c73ad087c78d69471000091", "snippets": [ { "offsetInBeginSection": 489, "offsetInEndSection": 755, "text": "Thus studies were conducted to examine the effects of lumacaftor alone and lumacaftor in combination with ivacaftor (i.e., ORKAMBI) on the ability of human CF ( del508Phe/ del508Phe) monocyte-derived macrophages (MDMs) to phagocytose and kill Pseudomonas aeruginosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29146575", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 852, "text": "In recent years, two modulators, ivacaftor (Kalydeco) and lumacaftor/ivacaftor (Orkambi), have been approved by the U.S. Food and Drug Administration to treat CF patients with certain CFTR mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29351449", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 423, "text": "Recently, ORKAMBI, a combination therapy that includes a corrector of the processing defect of F508del-CFTR (lumacaftor or VX-809) and a potentiator of channel activity (ivacaftor or VX-770), was approved for CF patients homozygous for this mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29903751", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 296, "text": "The recent US Food and Drug Administration (FDA) approval of lumacaftor combined with ivacaftor (Orkambi) targets patients with the F508del-CFTR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27804127", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 611, "text": "In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769592", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 663, "text": "Areas covered: In 2016, the Food and Drug Administration and the European Commission approved LUM/IVA (Orkambi), a CFTR modulator that includes both a CFTR corrector and potentiator, for CF patients homozygous for the F508del CFTR mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28891346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "The combination therapy of lumacaftor and ivacaftor (Orkambi\u00ae) is approved for patients bearing the major cystic fibrosis (CF) mutation: \u0394F508 It has been predicted that Orkambi\u00ae could treat patients with rarer mutations of similar \"theratype\"; however, a standardized approach confirming efficacy in these cohorts has not been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28667089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "ORKAMBI (ivacaftor-lumacaftor [LUMA]) and KALYDECO (ivacaftor; IVA) are two new breakthrough cystic fibrosis (CF) drugs that directly modulate the activity and trafficking of the defective CFTR underlying the CF disease state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27792891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Ivacaftor is currently used for the treatment of cystic fibrosis as both monotherapy (Kalydeco; Vertex Pharmaceuticals, Boston, MA) and combination therapy with lumacaftor (Orkambi; Vertex Pharmaceuticals).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Lisinopril oral solution (Qbrelis) for the treatment of hypertension, heart failure, and acute myocardial infarction; etanercept-szzs (Erelzi) for multiple autoimmune disorders; and lumacaftor/ivacaftor (Orkambi) for cystic fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Sacubitril/valsartan (Entresto) for chronic heart failure; brexpiprazole (Rexulti) for major depressive disorder and schizophrenia; and lumacaftor/ivacaftor (Orkambi) for cystic fibrosis involving specific CFTR mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26417173", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 295, "text": "The recent US Food and Drug Administration (FDA) approval of lumacaftor combined with ivacaftor (Orkambi) targets patients with the F508del-CFTR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27804127", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Altering Metabolic Profiles of Drugs by Precision Deuteration 2: Discovery of a Deuterated Analog of Ivacaftor with Differentiated Pharmacokinetics for Clinical Development.Ivacaftor is currently used for the treatment of cystic fibrosis as both monotherapy (Kalydeco; Vertex Pharmaceuticals, Boston, MA) and combination therapy with lumacaftor (Orkambi; Vertex Pharmaceuticals). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611092", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 417, "text": "Development of HPLC and LC-MS/MS methods for the analysis of ivacaftor, its major metabolites and lumacaftor in plasma and sputum of cystic fibrosis patients treated with ORKAMBI or KALYDECO.ORKAMBI (ivacaftor-lumacaftor [LUMA]) and KALYDECO (ivacaftor; IVA) are two new breakthrough cystic fibrosis (CF) drugs that directly modulate the activity and trafficking of the defective CFTR underlying the CF disease state. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27792891", "endSection": "title" }, { "offsetInBeginSection": 466, "offsetInEndSection": 689, "text": "In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "The combination therapy of lumacaftor and ivacaftor (Orkambi\u00ae) is approved for patients bearing the major cystic fibrosis (CF) mutation: \u0394F508 It has been predicted that Orkambi\u00ae could treat patients with rarer mutations of similar theratype; however, a standardized approach confirming efficacy in these cohorts has not been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28667089", "endSection": "abstract" } ] }, { "body": "List available R packages for processing NanoString data", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "http://www.ncbi.nlm.nih.gov/pubmed/29112706" ], "ideal_answer": [ "NanoStringNorm and NanoStringNormCNV." ], "exact_answer": [ [ "NanoStringNorm" ], [ "NanoStringNormCNV" ] ], "type": "list", "id": "5c6c46677c78d69471000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "NanoStringNorm: an extensible R package for the pre-processing of NanoString mRNA and miRNA data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 843, "text": "The NanoString nCounter Platform is a new and promising technology for measuring nucleic acid abundances. It has several advantages over PCR-based techniques, including avoidance of amplification, direct sequence interrogation and digital detection for absolute quantification. These features minimize aspects of experimental error and hold promise for dealing with challenging experimental conditions such as archival formalin-fixed paraffin-embedded samples. However, systematic inter-sample technical artifacts caused by variability in sample preservation, bio-molecular extraction and platform fluctuations must be removed to ensure robust data.RESULTS: To facilitate this process and to address these issues for NanoString datasets, we have written a pre-processing package called NanoStringNorm in the R statistical language.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "NanoStringNormCNV: pre-processing of NanoString CNV data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 675, "text": "The NanoString System is a well-established technology for measuring RNA and DNA abundance. Although it can estimate copy number variation, relatively few tools support analysis of these data. To address this gap, we created NanoStringNormCNV, an R package for pre-processing and copy number variant calling from NanoString data. This package implements algorithms for pre-processing, quality-control, normalization and copy number variation detection. A series of reporting and data visualization methods support exploratory analyses. To demonstrate its utility, we apply it to a new dataset of 96 genes profiled on 41 prostate tumour and 24 matched normal samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 337, "text": "To address this gap, we created NanoStringNormCNV, an R package for pre-processing and copy number variant calling from NanoString data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Summary\nThe NanoString System is a well-established technology for measuring RNA and DNA abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "MOTIVATION\nThe NanoString nCounter Platform is a new and promising technology for measuring nucleic acid abundances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "MOTIVATION The NanoString nCounter Platform is a new and promising technology for measuring nucleic acid abundances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Summary The NanoString System is a well-established technology for measuring RNA and DNA abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 836, "text": "Availability and implementation NanoStringNormCNV is implemented in R and is freely available at http://labs.oicr.on.ca/boutros-lab/software/nanostringnormcnv.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "NanoStringNorm: an extensible R package for the pre-processing of NanoString mRNA and miRNA data.The NanoString nCounter Platform is a new and promising technology for measuring nucleic acid abundances. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "MOTIVATION: The NanoString nCounter Platform is a new and promising technology for measuring nucleic acid abundances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 861, "text": "However, systematic inter-sample technical artifacts caused by variability in sample preservation, bio-molecular extraction and platform fluctuations must be removed to ensure robust data.
RESULTS: To facilitate this process and to address these issues for NanoString datasets, we have written a pre-processing package called NanoStringNorm in the R statistical language.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Summary: The NanoString System is a well-established technology for measuring RNA and DNA abundance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 345, "text": "To address this gap, we created NanoStringNormCNV, an R package for pre-processing and copy number variant calling from NanoString data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 997, "text": "To demonstrate its utility, we apply it to a new dataset of 96 genes profiled on 41 prostate tumour and 24 matched normal samples.
Availability and implementation: NanoStringNormCNV is implemented in R and is freely available at http://labs.oicr.on.ca/boutros-lab/software/nanostringnormcnv.
Contact: paul.boutros@oicr.on.ca.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29112706", "endSection": "abstract" } ] }, { "body": "Which disease is PGT121 used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29321310" ], "ideal_answer": [ "The broadly neutrilizing antibody PGT121 is being tested against HIV-1." ], "exact_answer": [ "HIV", "AIDS" ], "type": "factoid", "id": "5c65901c7c78d69471000008", "snippets": [ { "offsetInBeginSection": 308, "offsetInEndSection": 570, "text": "We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321310", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1257, "text": "In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321310", "endSection": "abstract" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1873, "text": "We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321310", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of anlotinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30098152", "http://www.ncbi.nlm.nih.gov/pubmed/29943374", "http://www.ncbi.nlm.nih.gov/pubmed/29438373", "http://www.ncbi.nlm.nih.gov/pubmed/30139768", "http://www.ncbi.nlm.nih.gov/pubmed/30032842", "http://www.ncbi.nlm.nih.gov/pubmed/28953502", "http://www.ncbi.nlm.nih.gov/pubmed/27716285", "http://www.ncbi.nlm.nih.gov/pubmed/29446853", "http://www.ncbi.nlm.nih.gov/pubmed/29620050", "http://www.ncbi.nlm.nih.gov/pubmed/29454091", "http://www.ncbi.nlm.nih.gov/pubmed/29764596", "http://www.ncbi.nlm.nih.gov/pubmed/30231931", "http://www.ncbi.nlm.nih.gov/pubmed/30146257" ], "ideal_answer": [ "Anlotinib is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), stem cell factor receptor (C-kit), platelet-derived growth factor (PDGF\u03b2), and fibroblast growth factor receptors (FGFR1, FGFR2, and FGFR3). It is used for treatment of cancer." ], "type": "summary", "id": "5c663c547c78d69471000014", "snippets": [ { "offsetInBeginSection": 133, "offsetInEndSection": 265, "text": "Anlotinib, a multi-kinase inhibitor, has already shown antitumor effects in various types of carcinoma in a phase I clinical trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30139768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "OBJECTIVES: AL3818 (anlotinib) is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), stem cell factor receptor (C-kit), platelet-derived growth factor (PDGF\u03b2), and fibroblast growth factor receptors (FGFR1, FGFR2, and FGFR3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28953502", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 482, "text": "In the present study, we detailed the pharmacological properties of anlotinib, a highly potent and selective VEGFR2 inhibitor, in preclinical models. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446853", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 678, "text": "In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing assay, chamber directional migration assay and tube formation assay indicated that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation of capillary-like tubes in endothelial cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454091", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1143, "text": "Mechanistically, anlotinib inhibits the activation of VEGFR2, PDGFR\u03b2 and FGFR1 as well their common downstream ERK signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2, PDGFR\u03b2 and FGFR1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454091", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND: Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29438373", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 652, "text": "Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29764596", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1305, "text": "The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30231931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Importance\nAnlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30098152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "OBJECTIVES\nAnlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD \u03b1/\u03b2, c-Kit and Ret.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30032842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "BACKGROUND\nAnlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR \u03b1/\u03b2, c-Kit, and Ret.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27716285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30231931", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30231931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND\nAnlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29438373", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1559, "text": "Collectively, these results indicate that anlotinib is a well-tolerated, orally active VEGFR2 inhibitor that targets angiogenesis in tumor growth, and support ongoing clinical evaluation of anlotinib for a variety of malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446853", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 664, "text": "Anlotinib occupied the ATP-binding pocket of VEGFR2 tyrosine kinase and showed high selectivity and inhibitory potency (IC50 <1\u00a0nmol/L) for VEGFR2 relative to other tyrosine kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Although anlotinib, a multi-targeted receptor tyrosine kinase inhibitor has been reported have antitumor effects in many preclinical and clinical trials, little is known about its effect on hepatocellular carcinoma (HCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30146257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Importance Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30098152", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 308, "text": "Anlotinib is an oral small molecule inhibitor of multiple receptor tyrosine kinases, with a broad spectrum of inhibitory effects on tumour angiogenesis and growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29943374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "BACKGROUND Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR \u03b1/\u03b2, c-Kit, and Ret.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27716285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "OBJECTIVES Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD \u03b1/\u03b2, c-Kit and Ret.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30032842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29438373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVES: Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD \u03b1/\u03b2, c-Kit and Ret.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30032842", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1220, "text": "The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30231931", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 458, "text": "In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD \u03b1/\u03b2, c-Kit and Ret.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30032842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Pharmacokinetics and disposition of anlotinib, an oral tyrosine kinase inhibitor, in experimental animal species.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29620050", "endSection": "title" } ] }, { "body": "Describe Canvas SPW", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028893" ], "ideal_answer": [ "Whole genome sequencing is becoming a diagnostics of choice for the identification of rare inherited and de novo copy number variants in families with various pediatric and late-onset genetic diseases. Joint variant calling in pedigrees is hampered by the complexity of consensus breakpoint alignment across samples within an arbitrary pedigree structure. Canvas SPW is a tool developed for the identification of inherited and de novo copy number variants from pedigree sequencing data. Canvas SPW supports a number of family structures and provides a wide range of scoring and filtering options to automate and streamline identification of de novo variants. The tool is available for download from https://github.com/Illumina/canvas." ], "type": "summary", "id": "5c6d8f4c7c78d6947100003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Canvas SPW: calling de novo copy number variants in pedigrees.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 808, "text": "Whole genome sequencing is becoming a diagnostics of choice for the identification of rare inherited and de novo copy number variants in families with various pediatric and late-onset genetic diseases. However, joint variant calling in pedigrees is hampered by the complexity of consensus breakpoint alignment across samples within an arbitrary pedigree structure.Results: We have developed a new tool, Canvas SPW, for the identification of inherited and de novo copy number variants from pedigree sequencing data. Canvas SPW supports a number of family structures and provides a wide range of scoring and filtering options to automate and streamline identification of de novo variants.Availability and implementation: Canvas SPW is available for download from https://github.com/Illumina/canvas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 527, "text": "Results\nWe have developed a new tool, Canvas SPW, for the identification of inherited and de novo copy number variants from pedigree sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 699, "text": "Canvas SPW supports a number of family structures and provides a wide range of scoring and filtering options to automate and streamline identification of de novo variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 527, "text": "Results We have developed a new tool, Canvas SPW, for the identification of inherited and de novo copy number variants from pedigree sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 811, "text": "Availability and implementation Canvas SPW is available for download from https://github.com/Illumina/canvas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 544, "text": "However, joint variant calling in pedigrees is hampered by the complexity of consensus breakpoint alignment across samples within an arbitrary pedigree structure.
Results: We have developed a new tool, Canvas SPW, for the identification of inherited and de novo copy number variants from pedigree sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 979, "text": "Canvas SPW supports a number of family structures and provides a wide range of scoring and filtering options to automate and streamline identification of de novo variants.
Availability and implementation: Canvas SPW is available for download from https://github.com/Illumina/canvas.
Contact: sivakhno@illumina.com.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 756, "text": "Canvas SPW is available for download from https://github.com/Illumina/canvas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 506, "text": "We have developed a new tool, Canvas SPW, for the identification of inherited and de novo copy number variants from pedigree sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 678, "text": "Canvas SPW supports a number of family structures and provides a wide range of scoring and filtering options to automate and streamline identification of de novo variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028893", "endSection": "abstract" } ] }, { "body": "List phagosomal markers.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26928472", "http://www.ncbi.nlm.nih.gov/pubmed/18485117", "http://www.ncbi.nlm.nih.gov/pubmed/30201700", "http://www.ncbi.nlm.nih.gov/pubmed/29675446", "http://www.ncbi.nlm.nih.gov/pubmed/20829607" ], "ideal_answer": [ "Rab7\nLAMP1\nCathepsin D\nRab9\nV-ATPase \nCD63" ], "exact_answer": [ [ "Rab7" ], [ "LAMP1" ], [ "Cathepsin D" ], [ "Rab9" ], [ "V-ATPase" ], [ "CD63" ] ], "type": "list", "id": "5c76e6d27c78d694710000ac", "snippets": [ { "offsetInBeginSection": 1113, "offsetInEndSection": 1508, "text": "Monitoring of intracellular trafficking of H. somni with monoclonal antibodies to phagosomal markers indicated that the early phagosomal marker early endosome antigen 1 colocalized with all isolates tested, but only strains that could survive intracellularly did not colocalize with the late lysosomal marker lysosome-associated membrane protein 2 and prevented the acidification of phagosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30201700", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 964, "text": "late phagosomal markers viz. Rab7, Lysosomal Associated Membrane Protein 1, Cathepsin D, Rab9, and V-ATPase which indicate phagosome maturation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26928472", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 667, "text": "early phagosomal markers [such as, Ras-related proteins in the brain 5 (Rab5) and Transferrin receptor (TfR)], and a failure to acquire late phagosomal and lysosomal markers (such as Rab7 and LAMP1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29675446", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 726, "text": "late phagosomal markers CD63 and Rab7", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20829607", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 607, "text": " late phagosomal markers mannose-6-phosphate receptor (M6PR) and Rab7", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18485117", "endSection": "abstract" } ] }, { "body": "List bacterial families for which delafloxacin has been shown to be effective.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27216072", "http://www.ncbi.nlm.nih.gov/pubmed/27458220" ], "ideal_answer": [ "Delafloxacin has been shown to be effective against multiple gram-positive and gram-negative bacteria, including Strepotococcus pneumoniae, Haemophilus influenzae, Moraxella atarrhalis, Staphylococcus aureus, Klebsiella pneumoniae and more." ], "exact_answer": [ [ "Streptococcus pneumoniae" ], [ "Haemophilus influenzae" ], [ "Moraxella catarrhalis" ], [ "Staphylococcus aureus" ], [ "Klebsiella pneumoniae" ] ], "type": "list", "id": "5c0119f3133db5eb7800002b", "snippets": [ { "offsetInBeginSection": 135, "offsetInEndSection": 440, "text": "In this study, 200 Streptococcus pneumoniae (plus 30 levofloxacin-resistant isolates), 200 Haemophilus influenzae, and 100 Moraxella catarrhalis isolates selected primarily from the United States (2014) were tested against delafloxacin and comparator agents. Delafloxacin was the most potent agent tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458220", "endSection": "abstract" }, { "offsetInBeginSection": 2358, "offsetInEndSection": 2516, "text": "Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27216072", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 322, "text": "The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27216072", "endSection": "abstract" } ] }, { "body": "What is the cause of Sandhoff disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29847465", "http://www.ncbi.nlm.nih.gov/pubmed/29358305", "http://www.ncbi.nlm.nih.gov/pubmed/29900534", "http://www.ncbi.nlm.nih.gov/pubmed/30236619" ], "ideal_answer": [ "Sandhoff disease (SD) is a genetic disorder caused by a mutation of the \u03b2-subunit gene \u03b2-hexosaminidase B (HexB) in humans, which results in the massive accumulation of the ganglioside GM2 and related glycosphingolipids in the nervous system." ], "exact_answer": [ "Sandhoff disease (SD) is caused by a mutation of the \u03b2-subunit gene \u03b2-hexosaminidase B (HexB) in humans" ], "type": "factoid", "id": "5c78080e7c78d694710000ae", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Sandhoff disease (SD) is a genetic disorder caused by a mutation of the \u03b2-subunit gene \u03b2-hexosaminidase B (HexB) in humans, which results in the massive accumulation of the ganglioside GM2 and related glycosphingolipids in the nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29847465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of \u03b2-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358305", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 579, "text": "Sandhoff disease results from the defective activity of \u03b2-hexosaminidase, leading to accumulation of ganglioside GM2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29900534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Sandhoff disease (SD) results from mutations in the HEXB gene, subsequent deficiency of N-acetyl-\u03b2-hexosaminidase (Hex) and accumulation of GM2 gangliosides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236619", "endSection": "abstract" } ] }, { "body": "Are there tools for reviewing variant calls?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29092934", "http://www.ncbi.nlm.nih.gov/pubmed/29346510" ], "ideal_answer": [ "Yes. Tools such as the Variant InsPector and Expert Rating tool (VIPER) have been developed that speed up the manual inspection of variant calls by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10 000 calls." ], "exact_answer": "yes", "type": "yesno", "id": "5c6da11e7c78d69471000042", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "VIPER: a web application for rapid expert review of variant calls.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29346510", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1041, "text": "With the rapid development in next-generation sequencing, cost and time requirements for genomic sequencing are decreasing, enabling applications in many areas such as cancer research. Many tools have been developed to analyze genomic variation ranging from single nucleotide variants to whole chromosomal aberrations. As sequencing throughput increases, the number of variants called by such tools also grows. Often employed manual inspection of such calls is thus becoming a time-consuming procedure. We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10 000 calls.Availability and implementation: VIPER is implemented in Java and Javascript and is freely available at https://github.com/MarWoes/viper.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29346510", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Variant Review with the Integrative Genomics Viewer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092934", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "VIPER: a web application for rapid expert review of variant calls.Supplementary data are available at Bioinformatics online.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29346510", "endSection": "title" }, { "offsetInBeginSection": 511, "offsetInEndSection": 672, "text": "We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29346510", "endSection": "abstract" } ] }, { "body": "Name one CCR4 targeted drug.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29414279" ], "ideal_answer": [ "Mogamulizumab is an anti-CCR4 monoclonal antibody." ], "exact_answer": [ "Mogamulizumab" ], "type": "factoid", "id": "5c65468ce842deac6700001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29414279", "endSection": "title" }, { "offsetInBeginSection": 370, "offsetInEndSection": 494, "text": "We evaluated mogamulizumab, a humanized anti-CCR4 monoclonal antibody that targets infected cells, in patients with HAM-TSP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29414279", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of cemiplimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30456447", "http://www.ncbi.nlm.nih.gov/pubmed/29666026", "http://www.ncbi.nlm.nih.gov/pubmed/30377167", "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "http://www.ncbi.nlm.nih.gov/pubmed/29934319" ], "ideal_answer": [ "Cemiplimab is human programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and blocks its interaction with programmed death ligands 1 (PD-L1) and 2 (PD-L2). It is approved to treat patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for surgery or radiation." ], "type": "summary", "id": "5c6b78b77c78d69471000028", "snippets": [ { "offsetInBeginSection": 1867, "offsetInEndSection": 2082, "text": "Phase II studies using anti-PD-1 molecules, nivolumab and pembrolizumab are ongoing, and GOG 3016, the first phase III randomized trial of a checkpoint inhibitor (cemiplimab) in cervical cancer, recently activated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29666026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29863979", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "PD-1 blockade with cemiplimab has antitumor activity with adverse events similar to other PD-1 inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The FDA greenlighted the PD-1 inhibitor cemiplimab to treat patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for surgery or radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30377167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Cemiplimab (LIBTAYO\u00ae; cemiplimab-rwlc), a human programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and blocks its interaction with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Regeneron Pharmaceuticals and Sanofi Genzyme. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30456447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Cemiplimab (LIBTAYO\u00ae; cemiplimab-rwlc), a human programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and blocks its interaction with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Regeneron Pharmaceuticals and Sanofi Genzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30456447", "endSection": "abstract" }, { "offsetInBeginSection": 1867, "offsetInEndSection": 2081, "text": "Phase II studies using anti-PD-1 molecules, nivolumab and pembrolizumab are ongoing, and GOG 3016, the first phase III randomized trial of a checkpoint inhibitor (cemiplimab) in cervical cancer, recently activated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29666026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "PD-1 blockade with cemiplimab has antitumor activity with adverse events similar to other PD-1 inhibitors.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934319", "endSection": "abstract" } ] }, { "body": "Which algorithm has been developed for finding conserved non-coding elements (CNEs) in genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30423090" ], "ideal_answer": [ "CNEFinder is a tool for identifying CNEs between two given DNA sequences with user-defined criteria." ], "exact_answer": [ "CNEFinder" ], "type": "factoid", "id": "5c51f01e07ef653866000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "CNEFinder: finding conserved non-coding elements in genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 756, "text": "We fill this gap by presenting CNEFinder; a tool for identifying CNEs between two given DNA sequences with user-defined criteria. The results presented here show the tool's ability of identifying CNEs accurately and efficiently.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "CNEFinder: finding conserved non-coding elements in genomes.Free software under the terms of the GNU GPL (https://github.com/lorrainea/CNEFinder).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "title" }, { "offsetInBeginSection": 421, "offsetInEndSection": 675, "text": "Currently, there are no tools published in the literature for systematically identifying CNEs in genomes.
Results: We fill this gap by presenting CNEFinder; a tool for identifying CNEs between two given DNA sequences with user-defined criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 637, "text": "We fill this gap by presenting CNEFinder; a tool for identifying CNEs between two given DNA sequences with user-defined criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "abstract" } ] }, { "body": "What causes Bathing suit Ichthyosis(BSI)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22801880", "http://www.ncbi.nlm.nih.gov/pubmed/28403434", "http://www.ncbi.nlm.nih.gov/pubmed/25209454", "http://www.ncbi.nlm.nih.gov/pubmed/16968736", "http://www.ncbi.nlm.nih.gov/pubmed/20522418" ], "ideal_answer": [ "Bathing suit ichthyosis (BSI) is a rare variant of autosomal recessive congenital ichthyosis (ARCI) due to transglutaminase-1 gene (TGM1) mutations leading to a temperature sensitive phenotype." ], "exact_answer": [ "transglutaminase-1 gene (TGM1) mutations" ], "type": "factoid", "id": "5c531d8f7e3cb0e231000017", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 274, "text": "Bathing suit ichthyosis (BSI) is an uncommon phenotype classified as a minor variant of autosomal recessive congenital ichthyosis (ARCI).OBJECTIVES: We report a case of BSI in a 3-year-old Tunisian girl with a novel mutation of the transglutaminase 1 gene (TGM1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25209454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype.Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by pronounced scaling on the bathing suit areas but sparing of the extremities and the central face. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16968736", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Bathing suit ichthyosis.Bathing suit ichthyosis (BSI) is a rare variant of autosomal recessive lamellar ichthyosis due to transglutaminase-1 (TGase-1) gene mutations leading to a temperature sensitive phenotype. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20522418", "endSection": "title" }, { "offsetInBeginSection": 286, "offsetInEndSection": 404, "text": "Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28403434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Bathing suit ichthyosis (BSI) is a rare variant of autosomal recessive lamellar ichthyosis due to transglutaminase-1 (TGase-1) gene mutations leading to a temperature sensitive phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20522418", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 765, "text": "All of our patients with BSI or SICI carried at least 1 specific missense mutation in TGM1 concerning an arginine at position 307 or 315.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801880", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1291, "text": "Combined with data from the literature, these findings confirm the hypothesis that only a restricted spectrum of TGM1 mutations leads to a BSI and/or an SICI phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "BACKGROUND: Bathing suit ichthyosis (BSI) is an uncommon phenotype classified as a minor variant of autosomal recessive congenital ichthyosis (ARCI).
OBJECTIVES: We report a case of BSI in a 3-year-old Tunisian girl with a novel mutation of the transglutaminase 1 gene (TGM1).
CASE REPORT: This infant had been born with a collodion membrane encasing her entire body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25209454", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1629, "text": "The present case demonstrates this phenotype in a White Tunisian patient with a novel mutation of TGM1 (I304F) not previously reported in BSI.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25209454", "endSection": "abstract" }, { "offsetInBeginSection": 1380, "offsetInEndSection": 1482, "text": "Therefore, the same mutation of the transglutaminase 1 could result in either generalized ARCI or BSI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25209454", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 594, "text": "Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28403434", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 575, "text": "Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28403434", "endSection": "abstract" }, { "offsetInBeginSection": 1396, "offsetInEndSection": 1538, "text": "The present case demonstrates this phenotype in a White Tunisian patient with a novel mutation of TGM1 (I304F) not previously reported in BSI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25209454", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 722, "text": "All of our patients with BSI or SICI carried at least 1 specific missense mutation in TGM1 concerning an arginine at position 307 or 315.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801880", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 584, "text": "We report genotypic and phenotypic data from a series of 9 patients who were collodion babies and developed BSI or SICI owing to mutations in the transglutaminase-1 gene (TGM1), including 3 previously unreported missense mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22801880", "endSection": "abstract" } ] }, { "body": "What type of data does the UK biobank resource contain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30305743", "http://www.ncbi.nlm.nih.gov/pubmed/27773354" ], "ideal_answer": [ "The UK Biobank contains deep phenotyping and genomic data. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits." ], "exact_answer": [ [ "genomic data" ], [ "phenotypic data" ] ], "type": "list", "id": "5c5205137e3cb0e231000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "The UK Biobank resource with deep phenotyping and genomic data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30305743", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 732, "text": "The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30305743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "The UK Biobank resource with deep phenotyping and genomic data.The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30305743", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "BACKGROUND\nThe UK Biobank is a unique resource for biomedical research, with extensive phenotypic and genetic data on half a million adults from the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27773354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "BACKGROUND The UK Biobank is a unique resource for biomedical research, with extensive phenotypic and genetic data on half a million adults from the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27773354", "endSection": "abstract" } ] }, { "body": "Has ivosidenib been FDA approved for use against acute myeloid leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30093505" ], "ideal_answer": [ "The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia." ], "exact_answer": "yes", "type": "yesno", "id": "5c65495be842deac67000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30093505", "endSection": "abstract" } ] }, { "body": "Which two surgical methods were compared in the RAZOR trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30140466", "http://www.ncbi.nlm.nih.gov/pubmed/25626182", "http://www.ncbi.nlm.nih.gov/pubmed/29976469" ], "ideal_answer": [ "The RAZOR trial compared open radical cystectomy vs. robot-assisted radical cystectomy in patients with bladder cancer." ], "exact_answer": [ [ "open radical cystectomy" ], [ "robot-assisted radical cystectomy" ] ], "type": "list", "id": "5c7036127c78d69471000064", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29976469", "endSection": "title" }, { "offsetInBeginSection": 328, "offsetInEndSection": 1122, "text": "METHODS: The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged \u226518 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29976469", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 999, "text": "Results: Evidence from four single-centre randomised controlled trials and now the multicentre Randomized Trial of Open versus Robotic Cystectomy (RAZOR) trial demonstrate the oncological equivalence of RARC to ORC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30140466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The RAZOR (randomized open vs robotic cystectomy) trial: study design and trial update.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25626182", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 592, "text": "The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of 2-year progression-free survival (PFS). RAZOR is a multi-institutional, randomized, non-inferior, phase III trial that will enrol at least 320 patients with T1-T4, N0-N1, M0 bladder cancer with \u2248160 patients in both the RARC and ORC arms at 15 participating institutions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25626182", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1461, "text": "AZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2-year PFS. Full data from the RAZOR trial are not expected until 2016-2017.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25626182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of 2-year progression-free survival (PFS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25626182", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 1001, "text": "Results\nEvidence from four single-centre randomised controlled trials and now the multicentre Randomized Trial of Open versus Robotic Cystectomy (RAZOR) trial demonstrate the oncological equivalence of RARC to ORC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30140466", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 1001, "text": "Results Evidence from four single-centre randomised controlled trials and now the multicentre Randomized Trial of Open versus Robotic Cystectomy (RAZOR) trial demonstrate the oncological equivalence of RARC to ORC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30140466", "endSection": "abstract" } ] }, { "body": "Are Copy Number Variants (CNVs) depleted in regions of low mappability?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30137632" ], "ideal_answer": [ "No. Low-mappability regions are approximately 5 times more likely to harbor germline CNVs, in stark contrast to the nearly uniform distribution observed for somatic CNVs in 95 cancer genomes." ], "exact_answer": "no", "type": "yesno", "id": "5c51f44c07ef653866000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Human copy number variants are enriched in regions of low mappability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137632", "endSection": "title" }, { "offsetInBeginSection": 578, "offsetInEndSection": 1319, "text": "Applying PopSV to 640 human genomes, we find that low-mappability regions are approximately 5\u00a0times more likely to harbor germline CNVs, in stark contrast to the nearly uniform distribution observed for somatic CNVs in 95 cancer genomes. In addition to known enrichments in segmental duplication and near centromeres and telomeres, we also report that CNVs are enriched in specific types of satellite and in some of the most recent families of transposable elements. Finally, using this comprehensive approach, we identify 3455 regions with recurrent CNVs that were missing from existing catalogs. In particular, we identify 347 genes with a novel exonic CNV in low-mappability regions, including 29 genes previously associated with disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Human copy number variants are enriched in regions of low mappability.Copy number variants (CNVs) are known to affect a large portion of the human genome and have been implicated in many diseases. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137632", "endSection": "title" } ] }, { "body": "List potential reasons regarding why potentially important genes are ignored", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30226837" ], "ideal_answer": [ "Differences in attention can be explained, to a large extent, exclusively from a small set of identifiable chemical, physical, and biological properties of genes. Together with knowledge about homologous genes from model organisms, these features accurately predict the number of publications on individual human genes, the year of their first report, the levels of funding awarded by the National Institutes of Health (NIH), and the development of drugs against disease-associated genes." ], "exact_answer": [ [ "Identifiable chemical properties" ], [ "Identifiable physical properties" ], [ "Identifiable biological properties" ], [ "Knowledge about homologous genes from model organisms" ] ], "type": "list", "id": "5c5214207e3cb0e231000003", "snippets": [ { "offsetInBeginSection": 102, "offsetInEndSection": 634, "text": "Here, we demonstrate that these differences in attention can be explained, to a large extent, exclusively from a small set of identifiable chemical, physical, and biological properties of genes. Together with knowledge about homologous genes from model organisms, these features allow us to accurately predict the number of publications on individual human genes, the year of their first report, the levels of funding awarded by the National Institutes of Health (NIH), and the development of drugs against disease-associated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30226837", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 381, "text": "Here, we demonstrate that these differences in attention can be explained, to a large extent, exclusively from a small set of identifiable chemical, physical, and biological properties of genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30226837", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 296, "text": "Here, we demonstrate that these differences in attention can be explained, to a large extent, exclusively from a small set of identifiable chemical, physical, and biological properties of genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30226837", "endSection": "abstract" } ] }, { "body": "Which random forest method has been developed for detecting Copy Numbers Variants (CNVs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27597741" ], "ideal_answer": [ "CNV-RF Is a Random Forest-Based Copy Number Variation Detection Method Using Next-Generation Sequencing." ], "exact_answer": [ "CNV-RF" ], "type": "factoid", "id": "5c51f9dd07ef653866000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "CNV-RF Is a Random Forest-Based Copy Number Variation Detection Method Using Next-Generation Sequencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27597741", "endSection": "title" }, { "offsetInBeginSection": 441, "offsetInEndSection": 652, "text": "We describe the development and implementation of a bioinformatics algorithm, copy number variation-random forest (CNV-RF), that incorporates a machine learning component to identify CNVs from targeted NGS data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27597741", "endSection": "abstract" } ] }, { "body": "What is the indication for Truvada?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23226529", "http://www.ncbi.nlm.nih.gov/pubmed/24223514", "http://www.ncbi.nlm.nih.gov/pubmed/21632769", "http://www.ncbi.nlm.nih.gov/pubmed/19731560", "http://www.ncbi.nlm.nih.gov/pubmed/29902179", "http://www.ncbi.nlm.nih.gov/pubmed/28276922", "http://www.ncbi.nlm.nih.gov/pubmed/22581627", "http://www.ncbi.nlm.nih.gov/pubmed/22874836", "http://www.ncbi.nlm.nih.gov/pubmed/29068302", "http://www.ncbi.nlm.nih.gov/pubmed/26411737", "http://www.ncbi.nlm.nih.gov/pubmed/26270298", "http://www.ncbi.nlm.nih.gov/pubmed/27093238" ], "ideal_answer": [ "Truvada is used for HIV pre-exposure prophylaxis (PrEP) in high risk individuals", "pre-exposure prophylaxis (PrEP) and the recent approval by the FDA of the supplemental indication for Truvada as PrEP" ], "exact_answer": [ "Prevention of HIV infection" ], "type": "factoid", "id": "5c5f29a81a4c55d80b00001f", "snippets": [ { "offsetInBeginSection": 61, "offsetInEndSection": 178, "text": "pre-exposure prophylaxis (PrEP) and the recent approval by the FDA of the supplemental indication for Truvada as PrEP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24223514", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 545, "text": " tenofovir disoproxil fumarate 300 mg (TDF)/emtricitabine 200 mg (FTC) (Truvada, Gilead Sciences) as antiretroviral preexposure prophylaxis (PrEP) to reduce the risk for HIV acquisition ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22874836", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 849, "text": "In January 2011, following publication of evidence of safety and efficacy of daily oral tenofovir disoproxil fumarate 300 mg (TDF)/emtricitabine 200 mg (FTC) (Truvada, Gilead Sciences) as antiretroviral preexposure prophylaxis (PrEP) to reduce the risk for HIV acquisition among MSM in the iPrEx trial, CDC issued interim guidance to make available information and important initial cautions on the use of PrEP in this population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22874836", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 959, "text": "In this commentary, we review literature on sexual behavior change accompanying PrEP use, discuss risk compensation concerns and the &quot;Truvada whore&quot; stereotype as PrEP barriers, question the appropriateness of restricting PrEP access because of risk compensation, and consider sexual pleasure as a benefit of PrEP, an acceptable motive for seeking PrEP, and a core element of health. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26270298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "BACKGROUND\nDaily pre-exposure prophylaxis (PrEP) with Truvada (a combination of emtricitabine (FTC) and tenofovir (TFV) disoproxil fumarate (TDF)) is a novel HIV prevention strategy recently found to prevent HIV transmission in men who have sex with men and heterosexual couples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23226529", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 935, "text": "Its co-formulation with emtricitabine (Truvada) is particularly convenient for treating both HIV and HBV in co-infected individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19731560", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 702, "text": "In January 2011, following publication of evidence of safety and efficacy of daily oral tenofovir disoproxil fumarate 300 mg (TDF)/emtricitabine 200 mg (FTC) (Truvada, Gilead Sciences) as antiretroviral preexposure prophylaxis (PrEP) to reduce the risk for HIV acquisition among MSM in the iPrEx trial, CDC issued interim guidance to make available information and important initial cautions on the use of PrEP in this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22874836", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 298, "text": "Truvada (emtricitabine-tenofovir) is currently the only medication approved for PrEP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29902179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "BACKGROUND Daily pre-exposure prophylaxis (PrEP) with Truvada (a combination of emtricitabine (FTC) and tenofovir (TFV) disoproxil fumarate (TDF)) is a novel HIV prevention strategy recently found to prevent HIV transmission in men who have sex with men and heterosexual couples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23226529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Antiretroviral preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate [Truvada]) prevents HIV without penalizing sexual pleasure, and may even enhance pleasure (e.g., by reducing HIV-related anxiety).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26270298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The pre-exposure prophylaxis (PrEP) drug Truvada is a new HIV prevention technology that is predominantly promoted as relevant to HIV-negative gay men.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28276922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "INTRODUCTION The FEM-PrEP trial was a pre-exposure prophylaxis clinical trial to test the safety and efficacy of Truvada (tenofovir disoproxil fumarate and emtricitabine) in the prevention of human immunodeficiency virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26411737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Oral pre-exposure prophylaxis (PrEP) using the antiretroviral drug emtricitabine/tenofovir disoproxil fumarate (Truvada) has been shown to dramatically reduce the risk of HIV acquisition for women at higher risk of infection if taken daily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27093238", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 682, "text": "Third, Truvada can be used prophylactically to prevent transmission of HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22581627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Daily preexposure prophylaxis (PrEP) with Truvada (emtricitabine FTC and tenofovir disoproxil fumarate TDF) is a novel HIV prevention strategy recently found to reduce HIV incidence among men who have sex with men.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21632769", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 278, "text": "It is the only drug approved to prevent HIV infections, and Truvada is the key pharmaceutical component of pre-exposure prophylaxis, which is aimed at preventing, rather than treating, HIV infection and transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29068302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Daily pre-exposure prophylaxis (PrEP) with Truvada (a combination of emtricitabine (FTC) and tenofovir (TFV) disoproxil fumarate (TDF)) is a novel HIV prevention strategy recently found to prevent HIV transmission in men who have sex with men and heterosexual couples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23226529", "endSection": "abstract" } ] }, { "body": "Is Adar3 involved in learning and memory?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29719497" ], "ideal_answer": [ "Yes. Adar3 is involved in learning and memory in mice. Mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice." ], "exact_answer": "yes", "type": "yesno", "id": "5c5b2f4b1a4c55d80b000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Adar3 Is Involved in Learning and Memory in Mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719497", "endSection": "title" }, { "offsetInBeginSection": 265, "offsetInEndSection": 1291, "text": " The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Adar3 Is Involved in Learning and Memory in Mice.-deficient mice. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719497", "endSection": "title" } ] }, { "body": "List STING agonists.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29472271", "http://www.ncbi.nlm.nih.gov/pubmed/29505322", "http://www.ncbi.nlm.nih.gov/pubmed/29127039", "http://www.ncbi.nlm.nih.gov/pubmed/30079976", "http://www.ncbi.nlm.nih.gov/pubmed/29170142" ], "ideal_answer": [ "CDN 3'3'-cGAMP\ndimethylxanthenone-4-acetic acid \n\u03b1-Mangostin" ], "exact_answer": [ [ "CDN 3'3'-cGAMP" ], [ "dimethylxanthenone-4-acetic acid" ], [ "\u03b1-Mangostin" ] ], "type": "list", "id": "5c7ab080d774d0424000000b", "snippets": [ { "offsetInBeginSection": 763, "offsetInEndSection": 786, "text": " CDN 3'3'-cGAMP (cGAMP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29170142", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 815, "text": " STING agonist, dimethylxanthenone-4-acetic acid (DMXAA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29505322", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 209, "text": " various cyclic dinucleotide (CDN) STING agonists", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The xanthone derivate 5',6'-dimethylxanthenone-4-acetic acid (DMXAA, also known as ASA404 or vadimezan) is a potent agonist of murine STING (stimulator of interferon genes), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079976", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 58, "text": "\u03b1-Mangostin as an Agonist of Human STING", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079976", "endSection": "title" } ] }, { "body": "List drugs that were tested in the CheckMate 214 trial.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29587324", "http://www.ncbi.nlm.nih.gov/pubmed/29728867", "http://www.ncbi.nlm.nih.gov/pubmed/30332546", "http://www.ncbi.nlm.nih.gov/pubmed/29223605", "http://www.ncbi.nlm.nih.gov/pubmed/30187355", "http://www.ncbi.nlm.nih.gov/pubmed/29468108", "http://www.ncbi.nlm.nih.gov/pubmed/29562145" ], "ideal_answer": [ "CheckMate 214 clinical trial compared Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma." ], "exact_answer": [ [ "Nivolumab" ], [ "Ipilimumab" ], [ "Sunitinib" ] ], "type": "list", "id": "5c6dfdf27c78d69471000047", "snippets": [ { "offsetInBeginSection": 439, "offsetInEndSection": 919, "text": " In 2015, the pivotal phase III study CheckMate 025 led to the Food and Drug Administration approval of nivolumab in patients with aRCC who had received prior anti-angiogenic therapy, and in 2017, the phase III study CheckMate 214 showed that combined immunotherapy with nivolumab plus ipilimumab resulted in greater objective response rate and prolonged progression-free survival when compared with sunitinib in intermediate- and poor-risk patients with previously untreated aRCC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29468108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562145", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 586, "text": "BACKGROUND: Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.METHODS: We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562145", "endSection": "abstract" }, { "offsetInBeginSection": 2065, "offsetInEndSection": 2413, "text": "CONCLUSIONS: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 214 ClinicalTrials.gov number, NCT02231749 .).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29562145", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1331, "text": "Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42\u200a% vs. 27\u200a%, p\u200a<\u200a0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo\u200a+\u200aIpi has been not yet reached (28.2\u200a-\u200aNR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29587324", "endSection": "abstract" }, { "offsetInBeginSection": 1773, "offsetInEndSection": 2056, "text": "CheckMate 214, a phase III trial, demonstrated superior overall survival and objective response with combined checkpoint inhibitors compared to sunitinib in Treatment-Na\u00efve Advanced RCC among intermediate- and poor-risk group (Motzer et al. in N Engl J Med. 378(14):1277-1290, 2018).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29728867", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1039, "text": "First, the CheckMate 214 trial demonstrated an objective response rate and overall survival benefit for the combination of nivolumab plus ipilimumab in the intermediate- and poor-risk patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30187355", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 563, "text": "have recently published in the New England Journal of Medicine the findings of CheckMate 214 trial, using nivolumab and ipilimumab, a cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, versus sunitinib in previously untreated advanced RCC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30332546", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 491, "text": "CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-na\u00efve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29223605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29223605", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1179, "text": "Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42\u200a% vs. 27\u200a%, p\u200a<\u200a0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo\u200a+\u200aIpi has been not yet reached (28.2\u200a-\u200aNR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29587324", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1331, "text": "Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29587324", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 668, "text": "CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p\u200a=\u200a0.0006) and response rate (26\u200a% vs. 5\u200a%) as well as a favorable toxicity profile compared with Everolimus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29587324", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 920, "text": "In 2015, the pivotal phase III study CheckMate 025 led to the Food and Drug Administration approval of nivolumab in patients with aRCC who had received prior anti-angiogenic therapy, and in 2017, the phase III study CheckMate 214 showed that combined immunotherapy with nivolumab plus ipilimumab resulted in greater objective response rate and prolonged progression-free survival when compared with sunitinib in intermediate- and poor-risk patients with previously untreated aRCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29468108", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 443, "text": "have recently published in the New England Journal of Medicine the findings of CheckMate 214 trial, using nivolumab and ipilimumab, a cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, versus sunitinib in previously untreated advanced RCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30332546", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 964, "text": "First, the CheckMate 214 trial demonstrated an objective response rate and overall survival benefit for the combination of nivolumab plus ipilimumab in the intermediate- and poor-risk patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30187355", "endSection": "abstract" }, { "offsetInBeginSection": 1773, "offsetInEndSection": 2013, "text": "CheckMate 214, a phase III trial, demonstrated superior overall survival and objective response with combined checkpoint inhibitors compared to sunitinib in Treatment-Na\u00efve Advanced RCC among intermediate- and poor-risk group (Motzer et al.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29728867", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1182, "text": "Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42\u200a% vs. 27\u200a%, p\u200a<\u200a0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo\u200a+\u200aIpi has been not yet reached (28.2\u200a-\u200aNR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29587324", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1334, "text": "Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29587324", "endSection": "abstract" } ] }, { "body": "Mutations in which gene have been found in patients with the CLAPO syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29446767" ], "ideal_answer": [ "CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. In a cohort of 13 patients with CLAPO, five activating mutations have been identified in the PIK3CA gene in affected tissues from 6 of the 9 patients studied." ], "exact_answer": [ "PIK3CA" ], "type": "factoid", "id": "5c5b4a941a4c55d80b000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446767", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 804, "text": "CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.METHODS: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing.RESULTS: We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446767", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 927, "text": "CONCLUSION\nWe describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446767", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 927, "text": "CONCLUSION We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446767", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 962, "text": "Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.
METHODS: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing.
RESULTS: We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders.
CONCLUSION: We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446767", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 889, "text": "We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446767", "endSection": "abstract" } ] }, { "body": "What is CamurWeb?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30367574" ], "ideal_answer": [ "CamurWeb is a classification software and a large knowledge base for gene expression data of cancer. It is a web-based software that is able to extract multiple and equivalent classification models in form of logic formulas (\"if then\" rules) and to create a knowledge base of these rules that can be queried and analyzed. The method is based on an iterative classification procedure and an adaptive feature elimination technique that enables the computation of many rule-based models related to the cancer under study. CamurWeb includes a user friendly interface for running the software, querying the results, and managing the performed experiments." ], "type": "summary", "id": "5c608f0cc01990ff41000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "CamurWeb: a classification software and a large knowledge base for gene expression data of cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "title" }, { "offsetInBeginSection": 834, "offsetInEndSection": 2231, "text": "We propose CamurWeb, a new method and web-based software that is able to extract multiple and equivalent classification models in form of logic formulas (\"if then\" rules) and to create a knowledge base of these rules that can be queried and analyzed. The method is based on an iterative classification procedure and an adaptive feature elimination technique that enables the computation of many rule-based models related to the cancer under study. Additionally, CamurWeb includes a user friendly interface for running the software, querying the results, and managing the performed experiments. The user can create her profile, upload her gene expression data, run the classification analyses, and interpret the results with predefined queries. In order to validate the software we apply it to all public available RNA sequencing datasets from The Cancer Genome Atlas database obtaining a large open access knowledge base about cancer. CamurWeb is available at http://bioinformatics.iasi.cnr.it/camurweb .CONCLUSIONS: The experiments prove the validity of CamurWeb, obtaining many classification models and thus several genes that are associated to 21 different cancer types. Finally, the comprehensive knowledge base about cancer and the software tool are released online; interested researchers have free access to them for further studies and to design biological experiments in cancer research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "CamurWeb: a classification software and a large knowledge base for gene expression data of cancer.The experiments prove the validity of CamurWeb, obtaining many classification models and thus several genes that are associated to 21 different cancer types. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "title" }, { "offsetInBeginSection": 1842, "offsetInEndSection": 2011, "text": "CONCLUSIONS\nThe experiments prove the validity of CamurWeb, obtaining many classification models and thus several genes that are associated to 21 different cancer types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1085, "text": "RESULTS\nWe propose CamurWeb, a new method and web-based software that is able to extract multiple and equivalent classification models in form of logic formulas (\"if then\" rules) and to create a knowledge base of these rules that can be queried and analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1085, "text": "RESULTS We propose CamurWeb, a new method and web-based software that is able to extract multiple and equivalent classification models in form of logic formulas (\"if then\" rules) and to create a knowledge base of these rules that can be queried and analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 1102, "text": "This comprehensive and open access knowledge base is required to disseminate novel insights about cancer.
RESULTS: We propose CamurWeb, a new method and web-based software that is able to extract multiple and equivalent classification models in form of logic formulas (\"if then\" rules) and to create a knowledge base of these rules that can be queried and analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1062, "text": "We propose CamurWeb, a new method and web-based software that is able to extract multiple and equivalent classification models in form of logic formulas (if then rules) and to create a knowledge base of these rules that can be queried and analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367574", "endSection": "abstract" } ] }, { "body": "Describe SLIC-CAGE", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30404778" ], "ideal_answer": [ "SLIC-CAGE is a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. SLIC-CAGE can generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods." ], "type": "summary", "id": "5c51f16307ef653866000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "title" }, { "offsetInBeginSection": 720, "offsetInEndSection": 1241, "text": "Here, we present SLIC-CAGE, a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods, by generating a complex, high-quality library from mouse embryonic day 11.5 primordial germ cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 879, "text": "Here, we present SLIC-CAGE, a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1241, "text": "We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods, by generating a complex, high-quality library from mouse embryonic day 11.5 primordial germ cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1245, "text": "We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods, by generating a complex, high-quality library from mouse embryonic day 11.5 primordial germ cells.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "abstract" } ] }, { "body": "There is no drug available to prevent HIV infection, Pre-exposure prophylaxis (PrEP), yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26746652", "http://www.ncbi.nlm.nih.gov/pubmed/27900502", "http://www.ncbi.nlm.nih.gov/pubmed/28370177", "http://www.ncbi.nlm.nih.gov/pubmed/21799568", "http://www.ncbi.nlm.nih.gov/pubmed/29278542", "http://www.ncbi.nlm.nih.gov/pubmed/27177804", "http://www.ncbi.nlm.nih.gov/pubmed/28657199", "http://www.ncbi.nlm.nih.gov/pubmed/23570850", "http://www.ncbi.nlm.nih.gov/pubmed/23972284", "http://www.ncbi.nlm.nih.gov/pubmed/25987851" ], "ideal_answer": [ "Pre-exposure prophylaxis (PrEP) with the drug combination Truvada can substantially decrease HIV transmission in individuals at risk.", "The antiviral agent tenofovir is highly effective for the treatment of HIV and hepatitis B virus infections, and the older prodrug tenofovir disoproxil fumarate (TDF) is also a component of daily preexposure prophylaxis (PrEP) to reduce the risk of HIV infection in high-risk populations." ], "exact_answer": "no", "type": "yesno", "id": "5c5f2cef1a4c55d80b000022", "snippets": [ { "offsetInBeginSection": 26, "offsetInEndSection": 169, "text": "pre-exposure prophylaxis with generic tenofovir disoproxil fumarate/emtrictabine in London - analysis of pharmacokinetics, safety and outcomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657199", "endSection": "title" }, { "offsetInBeginSection": 19, "offsetInEndSection": 308, "text": "The antiviral agent tenofovir is highly effective for the treatment of HIV and hepatitis B virus infections, and the older prodrug tenofovir disoproxil fumarate (TDF) is also a component of daily preexposure prophylaxis (PrEP) to reduce the risk of HIV infection in high-risk populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29278542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23972284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27900502", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 332, "text": "HIV pre-exposure prophylaxis (PrEP) is a new approach that involves the ongoing use of antiretroviral medications by HIV-negative individuals to reduce the risk of HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25987851", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1254, "text": "CONCLUSIONS Combined ART + PrEP is likely to prevent more HIV infections than either strategy alone, but with higher prevalence of drug resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23570850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "INTRODUCTION Use of pre-exposure prophylaxis (PrEP) among people who inject drugs (PWID) has been shown to be effective in preventing HIV transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27177804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21799568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral medications (in combination) to prevent HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28370177", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 183, "text": "The most commonly used PrEP medication (Truvada
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28370177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26746652", "endSection": "abstract" } ] }, { "body": "Burosumab is used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29896030", "http://www.ncbi.nlm.nih.gov/pubmed/29679282", "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "http://www.ncbi.nlm.nih.gov/pubmed/30269120", "http://www.ncbi.nlm.nih.gov/pubmed/30207609", "http://www.ncbi.nlm.nih.gov/pubmed/29791829", "http://www.ncbi.nlm.nih.gov/pubmed/29381780", "http://www.ncbi.nlm.nih.gov/pubmed/29545670", "http://www.ncbi.nlm.nih.gov/pubmed/29947083" ], "ideal_answer": [ "Burosumab is a fully human IgG1 monoclonal antibody directed at fibroblast growth factor 23 (FGF23), is indicated for the treatment of X-linked hypophosphatemia (XLH), a condition associated with excessive FGF23 production." ], "exact_answer": [ "X-linked hypophosphatemia" ], "type": "factoid", "id": "5c6b7fb27c78d6947100002d", "snippets": [ { "offsetInBeginSection": 1356, "offsetInEndSection": 1480, "text": "In particular, a humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in patients with XLH and TIO. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29381780", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 792, "text": "In February 2018, the EMA granted subcutaneous burosumab conditional marketing authorization for the treatment of X-linked hypophosphataemia (XLH) with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons. In April 2018, the US FDA approved burosumab for the treatment of XLH in adults and children one year of age and older. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29679282", "endSection": "abstract" }, { "offsetInBeginSection": 2515, "offsetInEndSection": 2751, "text": "CONCLUSIONS: In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29791829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Burosumab-twza (Crysvita) for a rare inherited form of rickets; ibalizumab-uiyk (Trogarzo) for human immunodeficiency virus type 1 infection; and tildrakizumab-asmn (Ilumya) for adults with moderate-to-severe plaque psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29896030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29947083", "endSection": "title" }, { "offsetInBeginSection": 2106, "offsetInEndSection": 2234, "text": "These data support the conclusion that burosumab is a novel therapeutic addressing an important medical need in adults with XLH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29947083", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1075, "text": "A novel therapy for XLH directly targeting fibroblast growth factor-23 via a humanized monoclonal antibody (burosumab-twza/CRYSVITA, henceforth referred to just as burosumab) has emerged as an effective, and recently approved, pharmacological treatment for both children and adults. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30207609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Burosumab in X-linked hypophosphatemia: a profile of its use in the USA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Burosumab (Crysvita\u00ae), a fully human IgG1 monoclonal antibody directed at fibroblast growth factor 23 (FGF23), is indicated for the treatment of X-linked hypophosphatemia (XLH), a condition associated with excessive FGF23 production. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 993, "text": "In clinical trials, subcutaneous burosumab increased serum phosphorus levels in pediatric and adult patients with XLH, as well as significantly improving the severity of rickets in children, and improving pain, stiffness, physical functioning, and fracture/pseudofracture healing in adults. Burosumab is well tolerated by children and adults with XLH, with most treatment-emergent adverse events being of mild to moderate severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1092, "text": "Moreover, Burosumab is being tested as a potential treatment for patients with tumor-induced osteomalacia(TIO), which is the most prevalent form of acquired FGF23-related hypophosphatemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269120", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1577, "text": "In particular, a humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in patients with XLH and TIO. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29381780", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 804, "text": "In April 2018, the US FDA approved burosumab for the treatment of XLH in adults and children one year of age and older. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29679282", "endSection": "abstract" }, { "offsetInBeginSection": 905, "offsetInEndSection": 1045, "text": "Burosumab is well tolerated by children and adults with XLH, with most treatment-emergent adverse events being of mild to moderate severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 684, "text": "Inhibition of FGF23 by burosumab results in increased renal phosphate reabsorption and increased serum levels of phosphorus and active vitamin D. In February 2018, the EMA granted subcutaneous burosumab conditional marketing authorization for the treatment of X-linked hypophosphataemia (XLH) with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29679282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Burosumab (Crysvita\u00ae), a fully human IgG1 monoclonal antibody directed at fibroblast growth factor 23 (FGF23), is indicated for the treatment of X-linked hypophosphatemia (XLH), a condition associated with excessive FGF23 production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 993, "text": "Burosumab is well tolerated by children and adults with XLH, with most treatment-emergent adverse events being of mild to moderate severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 852, "text": "In clinical trials, subcutaneous burosumab increased serum phosphorus levels in pediatric and adult patients with XLH, as well as significantly improving the severity of rickets in children, and improving pain, stiffness, physical functioning, and fracture/pseudofracture healing in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459508", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 671, "text": "Inhibition of FGF23 by burosumab results in increased renal phosphate reabsorption and increased serum levels of phosphorus and active vitamin D. In February 2018, the EMA granted subcutaneous burosumab conditional marketing authorization for the treatment of X-linked hypophosphataemia (XLH) with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29679282", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 791, "text": "In April 2018, the US FDA approved burosumab for the treatment of XLH in adults and children one year of age and older.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29679282", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1224, "text": "This article summarizes the milestones in the development of burosumab leading to its first global approval in the EU for XLH in paediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29679282", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1479, "text": "In particular, a humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in patients with XLH and TIO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29381780", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 967, "text": "Moreover, Burosumab is being tested as a potential treatment for patients with tumor-induced osteomalacia(TIO), which is the most prevalent form of acquired FGF23-related hypophosphatemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269120", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1074, "text": "A novel therapy for XLH directly targeting fibroblast growth factor-23 via a humanized monoclonal antibody (burosumab-twza/CRYSVITA, henceforth referred to just as burosumab) has emerged as an effective, and recently approved, pharmacological treatment for both children and adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30207609", "endSection": "abstract" }, { "offsetInBeginSection": 2521, "offsetInEndSection": 2756, "text": "CONCLUSIONS In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29791829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Burosumab (KRN23) is a fully human monoclonal IgG1 antibody that binds excess fibroblast growth factor 23 (FGF23) and has been successfully tested in clinical trials in children with X-linked hypophosphatemic rickets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29545670", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 971, "text": "Moreover, Burosumab is being tested as a potential treatment for patients with tumor-induced osteomalacia(TIO), which is the most prevalent form of acquired FGF23-related hypophosphatemia.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269120", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 778, "text": "The safety and efficacy of a human anti-FGF23 antibody, KRN23 or burosumab, has been confirmed in adults and children with XLHR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269120", "endSection": "abstract" }, { "offsetInBeginSection": 2106, "offsetInEndSection": 2253, "text": "These data support the conclusion that burosumab is a novel therapeutic addressing an important medical need in adults with XLH.\u00a9 2018 The Authors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29947083", "endSection": "abstract" }, { "offsetInBeginSection": 2108, "offsetInEndSection": 2255, "text": "These data support the conclusion that burosumab is a novel therapeutic addressing an important medical need in adults with XLH.\u00a9 2018 The Authors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29947083", "endSection": "abstract" }, { "offsetInBeginSection": 2489, "offsetInEndSection": 2712, "text": "In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29791829", "endSection": "abstract" } ] }, { "body": "What is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "http://www.ncbi.nlm.nih.gov/pubmed/30063981" ], "ideal_answer": [ "Loss-of-function nuclear factor \u03baB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.", "Heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of common variable immunodeficiency (CVID), which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells." ], "exact_answer": [ "Heterozygous loss-of-function variants in NFKB1" ], "type": "factoid", "id": "5c629937e842deac67000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Loss-of-function nuclear factor \u03baB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 578, "text": "The genetic cause of primary immunodeficiency disease (PID) carries prognostic information.OBJECTIVE: We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource-Rare Diseases cohort.METHODS: In the predominantly European study population of principally sporadic unrelated PID cases (n\u00a0=\u00a0846), a novel Bayesian method identified nuclear factor \u03baB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "abstract" }, { "offsetInBeginSection": 1747, "offsetInEndSection": 1961, "text": "We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "abstract" }, { "offsetInBeginSection": 1743, "offsetInEndSection": 1968, "text": "CONCLUSION\nWe show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Monoallelic loss-of-function mutations in NFKB1 were recently recognized as the most common monogenic cause of common variable immunodeficiency (CVID).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30063981", "endSection": "abstract" }, { "offsetInBeginSection": 1743, "offsetInEndSection": 1968, "text": "CONCLUSION We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "abstract" } ] }, { "body": "List two indications of Letermovir?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28675594", "http://www.ncbi.nlm.nih.gov/pubmed/30004790", "http://www.ncbi.nlm.nih.gov/pubmed/29578577", "http://www.ncbi.nlm.nih.gov/pubmed/28967706", "http://www.ncbi.nlm.nih.gov/pubmed/29290671", "http://www.ncbi.nlm.nih.gov/pubmed/29746444", "http://www.ncbi.nlm.nih.gov/pubmed/29914965", "http://www.ncbi.nlm.nih.gov/pubmed/29361041", "http://www.ncbi.nlm.nih.gov/pubmed/29288370", "http://www.ncbi.nlm.nih.gov/pubmed/29998227" ], "ideal_answer": [ "Letermovir is approved for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant (HSCT)." ], "exact_answer": [ [ "prophylaxis of CMV infection" ], [ "CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant" ] ], "type": "list", "id": "5c6e01af7c78d69471000048", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Latanoprostene bunod ophthalmic solution (Vyzulta) for the reduction of intraocular pressure; letermovir (Prevymis) for prophylaxis of cytomegalovirus infection and disease after stem cell transplant; benralizumab (Fasenra) for the add-on maintenance treatment of severe asthma of an eosinophilic phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29290671", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 418, "text": "Letermovir has been approved in Canada and the USA for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant (HSCT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29288370", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 865, "text": "This article summarizes the milestones in the development of letermovir leading to its first global approval in Canada as well as the USA for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogeneic HSCT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29288370", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 828, "text": "A new terminase inhibitor, letermovir, recently proved effective against HCMV in phase III clinical trials, but the mechanism of action is unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29361041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Letermovir is being developed for human cytomegalovirus infection treatment and prophylaxis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Letermovir is a human cytomegalovirus terminase inhibitor for cytomegalovirus infection prophylaxis in hematopoietic stem cell transplant recipients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29578577", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Role of letermovir for prevention of cytomegalovirus infection after allogeneic haematopoietic stem cell transplantation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29746444", "endSection": "title" }, { "offsetInBeginSection": 369, "offsetInEndSection": 766, "text": "In this article, the role of the newly approved antiviral compound, letermovir, is reviewed.RECENT FINDINGS: Letermovir inhibits CMV by interfering viral terminase complex. In a phase 3 randomized placebo-controlled clinical study that enrolled 495 CMV-seropositive HSCT recipients, the primary end point of clinically significant CMV infection was significantly reduced by letermovir prophylaxis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29746444", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1167, "text": "SUMMARY: Letermovir is an important addition to the current strategies for CMV prevention after allogeneic HSCT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29746444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Letermovir is a human cytomegalovirus (CMV) terminase inhibitor recently approved as prophylaxis in stem cell transplant recipients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29914965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28675594", "endSection": "abstract" }, { "offsetInBeginSection": 1106, "offsetInEndSection": 1334, "text": "Expert commentary: With the introduction of letermovir, prevention of CMV infection in allo-HCT recipients may shift considerably, from a predominantly preemptive strategy to one that utilizes this novel therapy for prophylaxis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30004790", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 913, "text": "The positive results from the recently published Phase III study of letermovir for prevention of CMV infection in CMV-seropositive allo-HCT recipients led to its approval as a prophylactic agent for CMV in multiple countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30004790", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1445, "text": "Letermovir has shown promising clinical efficacy and is generally well tolerated, thus providing a favorable new option in the prophylaxis of CMV infection and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29998227", "endSection": "abstract" } ] }, { "body": "What is achalasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28568312", "http://www.ncbi.nlm.nih.gov/pubmed/24259423", "http://www.ncbi.nlm.nih.gov/pubmed/28827050", "http://www.ncbi.nlm.nih.gov/pubmed/28867969", "http://www.ncbi.nlm.nih.gov/pubmed/8286427", "http://www.ncbi.nlm.nih.gov/pubmed/12141811", "http://www.ncbi.nlm.nih.gov/pubmed/10381906", "http://www.ncbi.nlm.nih.gov/pubmed/28919276", "http://www.ncbi.nlm.nih.gov/pubmed/18223498", "http://www.ncbi.nlm.nih.gov/pubmed/25994244", "http://www.ncbi.nlm.nih.gov/pubmed/19253525", "http://www.ncbi.nlm.nih.gov/pubmed/28717439" ], "ideal_answer": [ "Achalasia is a primary esophageal motility disorder characterized by aperistalsis of the esophagus and failed relaxation of the lower esophageal sphincter that presents rarely in childhood.", "Achalasia is a primary esophageal motility disorder characterized by aperistalsis of the esophagus and failed relaxation of the lower esophageal sphincter that presents rarely in childhood. Idiopathic achalasia is a rare esophageal motor disorder. The pathophysiology of achalasia is largely unknown, and involves the destruction of ganglion cell in the esophageal myenteric plexus.", "achalasia is a primary esophageal motility disorder", "Achalasia is a primary esophageal motility disorder characterized by aperistalsis of the esophagus and failed relaxation of the lower esophageal sphincter that presents rarely in childhood. Idiopathic achalasia is a rare esophageal motor disorder.", "Achalasia is a rare idiopathic disease, associated with significant morbidity and negative impact on life quality. The disorder is characterized by impairments in the esophageal motility and loss of the lower esophageal sphincter (LES) relaxation." ], "type": "summary", "id": "5c536c427e3cb0e23100001d", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 201, "text": "Achalasia is a primary esophageal motility disorder characterized by aperistalsis of the esophagus and failed relaxation of the lower esophageal sphincter that presents rarely in childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28827050", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 78, "text": "Idiopathic achalasia is a rare esophageal motor disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28568312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The pathophysiology of achalasia is largely unknown, and involves the destruction of ganglion cell in the esophageal myenteric plexus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28919276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "BACKGROUND\nIdiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24259423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Achalasia is a motility disorder of the esophagus characterized by total loss of esophageal peristalsis and by defective lower esophageal sphincter function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8286427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "BACKGROUND\nAchalasia is defined manometrically by an aperistaltic esophagus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18223498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Achalasia is one of the most studied esophageal motility disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28867969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "BACKGROUND & AIMS\nIdiopathic achalasia is a motility disorder of the esophagus characterized by incomplete relaxation of the lower esophageal sphincter and a loss of normal peristaltic activity in the body of the esophagus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10381906", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Achalasia is a disorder characterized by abnormal motility of the esophageal body and the lower esophageal sphincter, resulting in dysphagia, regurgitation, and chest pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12141811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Achalasia is a chronic incurable esophageal motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and loss of esophageal peristalsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28717439", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 580, "text": "Achalasia is a rare esophageal motility disorder, characterized by its distinct motility pattern with absent or incomplete lower esophageal sphincter (LES) relaxations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25994244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Achalasia is an infrequent primary motility disorder of the esophagus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19253525", "endSection": "abstract" } ] }, { "body": "Does allele phasing improve the phylogenetic utility of ultraconserved elements?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29771371" ], "ideal_answer": [ "Yes. Allele phasing greatly improves the phylogenetic utility of ultraconserved elements. Analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences." ], "exact_answer": "yes", "type": "yesno", "id": "5c52cde87e3cb0e23100000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29771371", "endSection": "title" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1969, "text": "Our empirical analyses of Ultraconserved Element (UCE) locus data collected from the South American hummingbird genus Topaza demonstrate that phased allele sequences carry sufficient phylogenetic information to infer the genetic structure, lineage divergence, and biogeographic history of a genus that diversified during the last three million years. The phylogenetic results support the recognition of two species, and suggest a high rate of gene flow across large distances of rainforest habitats but rare admixture across the Amazon River. Our simulations provide evidence that analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29771371", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements.Advances in high-throughput sequencing techniques now allow relatively easy and affordable sequencing of large portions of the genome, even for nonmodel organisms. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29771371", "endSection": "title" } ] }, { "body": "What is Burning Mouth Syndrome(BMS)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17439072", "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "http://www.ncbi.nlm.nih.gov/pubmed/20561063", "http://www.ncbi.nlm.nih.gov/pubmed/23772971", "http://www.ncbi.nlm.nih.gov/pubmed/29284330", "http://www.ncbi.nlm.nih.gov/pubmed/23201368", "http://www.ncbi.nlm.nih.gov/pubmed/17559486", "http://www.ncbi.nlm.nih.gov/pubmed/17849966", "http://www.ncbi.nlm.nih.gov/pubmed/20415926", "http://www.ncbi.nlm.nih.gov/pubmed/28247977", "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "http://www.ncbi.nlm.nih.gov/pubmed/12794658", "http://www.ncbi.nlm.nih.gov/pubmed/24096230", "http://www.ncbi.nlm.nih.gov/pubmed/26863819", "http://www.ncbi.nlm.nih.gov/pubmed/23589947", "http://www.ncbi.nlm.nih.gov/pubmed/19302167", "http://www.ncbi.nlm.nih.gov/pubmed/29257770", "http://www.ncbi.nlm.nih.gov/pubmed/27207008", "http://www.ncbi.nlm.nih.gov/pubmed/26535101", "http://www.ncbi.nlm.nih.gov/pubmed/18624934", "http://www.ncbi.nlm.nih.gov/pubmed/15773524", "http://www.ncbi.nlm.nih.gov/pubmed/8982420", "http://www.ncbi.nlm.nih.gov/pubmed/18625105", "http://www.ncbi.nlm.nih.gov/pubmed/27209717", "http://www.ncbi.nlm.nih.gov/pubmed/26962284" ], "ideal_answer": [ "Burning Mouth Syndrome (BMS), a chronic intraoral burning sensation or dysesthesia without clinically evident causes, is one of the most common medically unexplained oral symptoms/syndromes. It predominately affects middle-aged women in the postmenopausal period. The condition is distinguished by burning symptoms of the oral mucosa and the absence of any clinical signs.", "Burning mouth syndrome (BMS) is a chronic oral pain syndrome that primarily affects peri- and postmenopausal women. It is characterized by oral mucosal burning and may be associated with dysgeusia, paresthesia, dysesthesia, and xerostomia." ], "type": "summary", "id": "5c5f39011a4c55d80b000027", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Burning mouth syndrome (BMS) is a chronic oral pain syndrome that primarily affects peri- and postmenopausal women. It is characterized by oral mucosal burning and may be associated with dysgeusia, paresthesia, dysesthesia, and xerostomia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28247977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Primary burning mouth syndrome (BMS) is defined as an \"intraoral burning or dysaesthetic sensation, recurring daily\u2026 more than 3 months, without clinically evident causative lesions\" (IHS 2013).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29257770", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 135, "text": "Burning mouth syndrome (BMS) is a chronic orofacial pain disorder that is defined by a burning sensation in the oral mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29284330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Burning mouth syndrome.Burning mouth syndrome is characterized by a burning sensation in the tongue or other oral sites, usually in the absence of clinical and laboratory findings. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "endSection": "title" }, { "offsetInBeginSection": 274, "offsetInEndSection": 413, "text": "Burning mouth syndrome is characterized by a burning, painful sensation of the oral mucosa that most commonly involves the anterior tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Burning mouth syndrome is a complicated, poorly understood, predominantly oral condition that affects more than 1 million people in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 601, "text": "Burning mouth syndrome is a common disorder, usually affecting elderly females, characterised by intractable pain and burning in the oral cavity, evident especially in the tongue, together with a normal mouth mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12794658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND\nBurning mouth syndrome is a disorder usually associated with an unexplained, prolonged sensation of burning inside the oral cavity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18624934", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 377, "text": "Burning mouth syndrome is an idiopathic pain disorder, which appears to be neuropathic in origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17849966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Burning mouth syndrome is characterized by a burning sensation in the tongue or other oral sites, usually in the absence of clinical and laboratory findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Burning mouth syndrome (BMS) is a predominantly oral condition characterized by the occurrence of a chronic burning that commonly involves the anterior tongue, painful sensation, dryness and taste alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15773524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The burning mouth syndrome is characterized by an unpleasant sensation of burning in the oral cavity, without clinical signs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8982420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND Burning mouth syndrome is a disorder usually associated with an unexplained, prolonged sensation of burning inside the oral cavity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18624934", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND Burning mouth syndrome is a burning sensation or stinging disorder affecting the oral mucosa in the absence of any clinical signs or mucosal lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19302167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Burning mouth syndrome is a chronic pain condition characterized by burning, painful sensations within the oral cavity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20561063", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "BACKGROUND Burning mouth syndrome (BMS) is common conditions that affects menopause women, patients suffer from sever burning sensation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26535101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Burning mouth syndrome (BMS) is characterized by burning pain in the tongue or other oral mucous membrane often associated with symptoms such as subjective dryness of the mouth, paraesthesia and altered taste for which no medical or dental cause can be found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20415926", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 308, "text": "When a burning sensation in the mouth is caused by local or systemic factors, it is called secondary burning mouth syndrome and when these factors are treated the pain will resolve.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23201368", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 441, "text": "Burning mouth syndrome is characterized by an intense burning or stinging sensation, preferably on the tongue or in other areas of mouth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation affecting the oral mucosa, often unaccompanied by mucosal lesions or other evident clinical signs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24096230", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 336, "text": "Burning mouth syndrome is a diagnosis of exclusion, which is used only after nutritional deficiencies, mucosal disease, fungal infections, hormonal disturbances and contact stomatitis have been ruled out.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27209717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Burning mouth syndrome (BMS) is a chronic disease characterized by burning of the oral mucosa associated with a sensation of dry mouth and/or taste alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18625105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Burning mouth syndrome (BMS) is characterized by burning sensations of the oral cavity in the absence of abnormalities of the oral mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17439072", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 422, "text": "Burning mouth syndrome generally presents as a triad: Mouth pain, alteration in taste, and altered salivation, in the absence of visible mucosal lesions in the mouth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27207008", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 499, "text": "We analyzed the etiopathogenesis of Burning Mouth Syndrome and of the burning oral sensation and currently, we could not find a consensus on the diagnosis and classification of BMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26863819", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Burning mouth syndrome (BMS) is multifactorial in origin which is typically characterized by burning and painful sensation in an oral cavity demonstrating clinically normal mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26962284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "According to the International Association for the Study of Pain, burning mouth Syndrome (BMS) is defined as a burning pain in the tongue or other oral mucous membrane in the absence of clinical signs or laboratory findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23589947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Burning mouth syndrome (BMS) is characterized by the presence of burning sensation of the oral mucosa in the absence of clinically apparent mucosal alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23772971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Burning mouth syndrome (BMS) refers to a chronic orofacial pain disorder usually unaccompanied by mucosal lesions or other clinical signs of organic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17559486", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 1174, "text": "Burning mouth syndrome may present as an idiopathic condition (primary BMS type) distinct from the symptom of oral burning that can potentially arise from various local or systemic abnormalities (secondary BMS type), including nutritional deficiencies, hormonal changes associated with menopause, local oral infections, denture-related lesions, xerostomia, hypersensitivity reactions, medications, and systemic diseases including diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17559486", "endSection": "abstract" } ] }, { "body": "When is serum AFP used as marker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28796412", "http://www.ncbi.nlm.nih.gov/pubmed/29154784", "http://www.ncbi.nlm.nih.gov/pubmed/28361205", "http://www.ncbi.nlm.nih.gov/pubmed/28582340", "http://www.ncbi.nlm.nih.gov/pubmed/28482112" ], "ideal_answer": [ "Serum \u03b1-Fetoprotein (AFP) is a widely used diagnostic biomarker, but it has limited sensitivity and is not elevated in all Hepato cellular carcinoma (HCC) cases so, we incorporate a second blood-based biomarker, des'\u03b3 carboxy-prothrombin (DCP), that has shown potential as a screening marker for HCC." ], "exact_answer": [ "in HCC", "Hepato cellular carcinoma" ], "type": "factoid", "id": "5c7839edd774d04240000003", "snippets": [ { "offsetInBeginSection": 1432, "offsetInEndSection": 1523, "text": "AFP serum were considered independent predictors for macrovascular invasion in HCC patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361205", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1537, "text": "Post-hepatectomy HLs of AFP and DCP are predictors of long-term outcome in patients with HCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28796412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Ovarian Sertoli-Leydig cell tumors (SLCTs) are uncommon neoplasms that are occasionally associated with an elevated level of serum alpha fetoprotein (AFP), a marker of germ cell neoplasms, particularly yolk sac tumor (YST). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28582340", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 609, "text": "Serum \u03b1-Fetoprotein (AFP) is a widely used diagnostic biomarker, but it has limited sensitivity and is not elevated in all HCC cases so, we incorporate a second blood-based biomarker, des'\u03b3 carboxy-prothrombin (DCP), that has shown potential as a screening marker for HCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28482112", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1427, "text": "In addition, AFP, a hepatic stem cell marker, was expressed at the highest level in the control groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29154784", "endSection": "abstract" } ] }, { "body": "Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25631286", "http://www.ncbi.nlm.nih.gov/pubmed/29698650", "http://www.ncbi.nlm.nih.gov/pubmed/26915272", "http://www.ncbi.nlm.nih.gov/pubmed/23379365", "http://www.ncbi.nlm.nih.gov/pubmed/29330303", "http://www.ncbi.nlm.nih.gov/pubmed/28932898", "http://www.ncbi.nlm.nih.gov/pubmed/22052352", "http://www.ncbi.nlm.nih.gov/pubmed/23077577", "http://www.ncbi.nlm.nih.gov/pubmed/17514901", "http://www.ncbi.nlm.nih.gov/pubmed/28148884", "http://www.ncbi.nlm.nih.gov/pubmed/23045389" ], "ideal_answer": [ "infectious proteins) were discovered by their outr\u00e9 genetic properties and have become important models for an array of human prion and amyloid diseases.", "Yeast prions have become important models for the study of the basic mechanisms underlying human amyloid diseases and normal yeast cells can eliminate the large majority of prion variants arising.", "Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions", "These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics." ], "exact_answer": "yes", "type": "yesno", "id": "5c5723a007647bbc4b000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28932898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Fibrous cross-\u03b2 aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330303", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1044, "text": "These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29698650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Yeast prions (infectious proteins) were discovered by their outr\u00e9 genetic properties and have become important models for an array of human prion and amyloid diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26915272", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 678, "text": "Yeast prions are models for both rare mammalian prion diseases and for several very common amyloidoses such as Alzheimer's disease, type 2 diabetes, and Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28148884", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1081, "text": "Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23379365", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 479, "text": "Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077577", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1048, "text": "Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23379365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28932898", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 376, "text": "Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077577", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 742, "text": "Here we summarize the results of studies of prions of the yeast Saccharomyces cerevisiae and of the use of yeast model for investigation of some human amyloidoses, such as prion diseases, Alzheimer's, Parkinson's, and Huntington's diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17514901", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1272, "text": "Yeast prions increasingly are serving as models for the understanding and treatment of many mammalian amyloidoses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25631286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Yeast prions, based on self-seeded highly ordered fibrous aggregates (amyloids), serve as a model for human amyloid diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23045389", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1048, "text": "These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29698650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The yeast system has provided considerable insight into the biology of amyloid and prions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22052352", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1046, "text": "Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23379365", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1294, "text": "We also review studies of the roles of chaperones, aggregate-collecting proteins, and other cellular components using yeast that have led the way in improving the understanding of similar processes that must be operating in many human amyloidoses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23379365", "endSection": "abstract" } ] }, { "body": "RV3-BB vaccine is used for prevention of which viral infection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26318715", "http://www.ncbi.nlm.nih.gov/pubmed/29688121", "http://www.ncbi.nlm.nih.gov/pubmed/28059609", "http://www.ncbi.nlm.nih.gov/pubmed/30145099", "http://www.ncbi.nlm.nih.gov/pubmed/23597719", "http://www.ncbi.nlm.nih.gov/pubmed/28481726" ], "ideal_answer": [ "The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth." ], "exact_answer": [ "rotavirus disease" ], "type": "factoid", "id": "5c6e05f37c78d69471000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Serological responses to rotavirus NSP2 following administration of RV3-BB human neonatal rotavirus vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688121", "endSection": "title" }, { "offsetInBeginSection": 196, "offsetInEndSection": 523, "text": "Serological responses to rotavirus NSP2 occur following wild-type infection; however, it is unknown if serological responses to NSP2 occur following administration of rotavirus vaccines. The phase IIa immunogenicity trial of RV3-BB provided an opportunity to investigate the serological responses to NSP2 following vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Molecular characterisation of rotavirus strains detected during a clinical trial of the human neonatal rotavirus vaccine (RV3-BB) in Indonesia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145099", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND: The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28059609", "endSection": "title" }, { "offsetInBeginSection": 197, "offsetInEndSection": 482, "text": "This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28059609", "endSection": "abstract" }, { "offsetInBeginSection": 1319, "offsetInEndSection": 1455, "text": "RESULTS: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28059609", "endSection": "abstract" }, { "offsetInBeginSection": 1886, "offsetInEndSection": 2164, "text": "CONCLUSIONS: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28059609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28481726", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28481726", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 269, "text": "RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28481726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "BACKGROUND The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145099", "endSection": "abstract" }, { "offsetInBeginSection": 1665, "offsetInEndSection": 1769, "text": "CONCLUSION A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597719", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 584, "text": "RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth.
METHODS: A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3\u00d710(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597719", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1804, "text": "Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant.
CONCLUSION: A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597719", "endSection": "abstract" }, { "offsetInBeginSection": 2545, "offsetInEndSection": 2673, "text": "A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26318715", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 254, "text": "RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597719", "endSection": "abstract" }, { "offsetInBeginSection": 1628, "offsetInEndSection": 1721, "text": "A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23597719", "endSection": "abstract" } ] }, { "body": "Is dupilumab effective for treatment of asthma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27334730", "http://www.ncbi.nlm.nih.gov/pubmed/29782217", "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "http://www.ncbi.nlm.nih.gov/pubmed/28979129", "http://www.ncbi.nlm.nih.gov/pubmed/28547386", "http://www.ncbi.nlm.nih.gov/pubmed/28971769", "http://www.ncbi.nlm.nih.gov/pubmed/28990423", "http://www.ncbi.nlm.nih.gov/pubmed/29036019", "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "http://www.ncbi.nlm.nih.gov/pubmed/29059087", "http://www.ncbi.nlm.nih.gov/pubmed/30167841", "http://www.ncbi.nlm.nih.gov/pubmed/29355679", "http://www.ncbi.nlm.nih.gov/pubmed/29939132", "http://www.ncbi.nlm.nih.gov/pubmed/29782224", "http://www.ncbi.nlm.nih.gov/pubmed/28478972" ], "ideal_answer": [ "Yes, dupilumab is effective for treatment of asthma. It works by simultaneous targeting of both IL-4 and IL-13 by blocking IL-4 receptor \u03b1." ], "exact_answer": "yes", "type": "yesno", "id": "5c6b7bee7c78d6947100002a", "snippets": [ { "offsetInBeginSection": 559, "offsetInEndSection": 773, "text": "The appropriate use of these biologics, and of those in development (e.g., benralizumab and dupilumab), should be aided by further understanding of asthma phenotypes and endotypes, utilizing appropriate biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059087", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 890, "text": "Simultaneous targeting of both IL-4 and IL-13 by blocking IL-4 receptor \u03b1 using dupilumab has yielded more consistent results in reducing asthma exacerbations and improving lung function, especially in patients with increased blood eosinophils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29036019", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 452, "text": "In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting \u03b22-agonists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355679", "endSection": "abstract" }, { "offsetInBeginSection": 1705, "offsetInEndSection": 1856, "text": "CONCLUSIONS: Dupilumab 300\u00a0mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355679", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 771, "text": "Small molecules (e.g. ligustrazine and SP600125) and large molecule antibodies (e.g. lebrikizumab, benralizumab, dupilumab) are being considered as novel agents for the pharmacotherapy of asthma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28971769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29782217", "endSection": "title" }, { "offsetInBeginSection": 2062, "offsetInEndSection": 2267, "text": "CONCLUSIONS: In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29782217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Dupilumab for the treatment of asthma.Dupilumab (REGN668/SAR231893), produced by a collaboration between Regeneron and Sanofi, is a monoclonal antibody currently in phase III for moderate-to-severe asthma. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "endSection": "title" }, { "offsetInBeginSection": 255, "offsetInEndSection": 383, "text": "Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Dupilumab (REGN668/SAR231893), produced by a collaboration between Regeneron and Sanofi, is a monoclonal antibody currently in phase III for moderate-to-severe asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 869, "text": "If confirmed, efficacy of dupilumab in both eosinophilic and non-eosinophilic severe asthma phenotype might represent an advantage over approved biologics for asthma, including omalizumab, mepolizumab, and reslizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1391, "text": "In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28979129", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 956, "text": "Expert opinion: Supported by a strategic mechanism of action, as well as by convincing preliminary clinical results, dupilumab currently appears to be a very promising biological drug for the treatment of severe uncontrolled asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28990423", "endSection": "abstract" }, { "offsetInBeginSection": 1462, "offsetInEndSection": 1570, "text": "All drugs decreased asthma exacerbations but the results were only significant for reslizumab and dupilumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30167841", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1158, "text": "Anti-IL-4 and IL-13 agents (dupilumab, lebrikizumab, and tralokinumab) which block different Th-2 inflammatory pathways and agents targeting the Th-17 inflammatory pathway in severe refractory asthma are under development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27334730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Dupilumab for the treatment of asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "endSection": "title" }, { "offsetInBeginSection": 687, "offsetInEndSection": 872, "text": "In addition, dupilumab is currently under phase\u00a0III development across the world for the treatment of asthma and nasal polyposis as well as for atopic dermatitis in paediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28547386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "BACKGROUND\nDupilumab (an anti-interleukin-4-receptor-\u03b1 monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28478972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Dupilumab: a novel treatment for asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Dupilumab for the treatment of asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28990423", "endSection": "title" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1062, "text": "The efficacy and safety profile of dupilumab in the treatment of allergic diseases has been tested for more than 10 years in a variety of large clinical trials in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29939132", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 495, "text": "Areas covered: Pathophysiological role of IL-4 and IL-13 in asthma; mechanism of action of dupilumab; pharmacology of IL-4 receptor; phase I and phase II studies with dupilumab; regulatory affairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 651, "text": "Expert opinion: Patients with severe asthma who are not sufficiently controlled with standard-of-care represent the target asthma population for dupilumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "endSection": "abstract" }, { "offsetInBeginSection": 1952, "offsetInEndSection": 2147, "text": "CONCLUSIONS In patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29782224", "endSection": "abstract" }, { "offsetInBeginSection": 1832, "offsetInEndSection": 2207, "text": "CONCLUSIONS In patients with persistent, moderate-to-severe asthma and elevated eosinophil levels who used inhaled glucocorticoids and LABAs, dupilumab therapy, as compared with placebo, was associated with fewer asthma exacerbations when LABAs and inhaled glucocorticoids were withdrawn, with improved lung function and reduced levels of Th2-associated inflammatory markers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 672, "text": "Expert opinion: Patients with severe asthma who are not sufficiently controlled with standard-of-care represent the target asthma population for dupilumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28085503", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 391, "text": "Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 977, "text": "Expert opinion: Supported by a strategic mechanism of action, as well as by convincing preliminary clinical results, dupilumab currently appears to be a very promising biological drug for the treatment of severe uncontrolled asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28990423", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 370, "text": "Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26428945", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1133, "text": "A recent trial showed that in patients with difficult-to-control asthma, dupilumab can markedly decrease asthma exacerbations and improve respiratory symptoms and lung function; these effects were paralleled by significant reductions in T-helper 2-associated inflammatory biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "endSection": "abstract" } ] }, { "body": "What is the role of the Mcm2-Ctf4-Pol\u03b1 axis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30244834" ], "ideal_answer": [ "The Mcm2-Ctf4-Pol\u03b1 axis facilitates parental histone H3-H4 transfer to lagging strands.", "The Mcm2-Ctf4-Pol\u03b1 Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands.", "The Mcm2-Ctf4-Pol\u03b1 Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands. Although essential for epigenetic inheritance, the transfer of parental histone (H3-H4)2 tetramers that contain epigenetic modifications to replicating DNA strands is poorly understood." ], "type": "summary", "id": "5c5410647e3cb0e23100001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The Mcm2-Ctf4-Pol\u03b1 Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30244834", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Although essential for epigenetic inheritance, the transfer of parental histone (H3-H4)2 tetramers that contain epigenetic modifications to replicating DNA strands is poorly understood. Here, we show that the Mcm2-Ctf4-Pol\u03b1 axis facilitates the transfer of parental (H3-H4)2 tetramers to lagging-strand DNA at replication forks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30244834", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 328, "text": "Here, we show that the Mcm2-Ctf4-Pol\u03b1 axis facilitates the transfer of parental (H3-H4)2 tetramers to lagging-strand DNA at replication forks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30244834", "endSection": "abstract" } ] }, { "body": "What is anophthalmia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29753094", "http://www.ncbi.nlm.nih.gov/pubmed/17522144", "http://www.ncbi.nlm.nih.gov/pubmed/26250054", "http://www.ncbi.nlm.nih.gov/pubmed/30515001", "http://www.ncbi.nlm.nih.gov/pubmed/20704474", "http://www.ncbi.nlm.nih.gov/pubmed/30262714", "http://www.ncbi.nlm.nih.gov/pubmed/27785411", "http://www.ncbi.nlm.nih.gov/pubmed/25071894", "http://www.ncbi.nlm.nih.gov/pubmed/28590501" ], "ideal_answer": [ "Microphthalmia, anophthalmia are the malformations of the eye, referring to a congenital absence, and a reduced size of the eyeball.", "Anophthalmia is the medical term for the absence of one or both eyes." ], "exact_answer": [ "absence of one or both eyes" ], "type": "factoid", "id": "5c674c287c78d6947100001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Microphthalmia, anophthalmia are the malformations of the eye, referring to a congenital absence, and a reduced size of the eyeball.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Anophthalmia is the congenital absence of ocular tissue from the orbit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20704474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Anophthalmia is a condition of the absence of an eye and the presence of a small eye within the orbit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Congenital anophthalmia is a rare eye anomaly which lacks a recognizable eye in the orbit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30262714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "SOX2 anophthalmia syndrome is an uncommon autosomal dominant syndrome caused by mutations in the SOX2 gene and clinically characterized by severe eye malformations (anophthalmia/microphthalmia) and extraocular anomalies mainly involving brain, esophagus, and genitalia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26250054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Introduction\nAnophthalmia is congenital absence of the eyes; it may be unilateral or bilateral.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Clinical anophthalmia is a rare inherited disease of the eye and phenotype refers to the absence of ocular tissue in the orbit of eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27785411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Introduction Anophthalmia is congenital absence of the eyes; it may be unilateral or bilateral.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30515001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17522144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Anophthalmia is a rare eye development anomaly resulting in absent ocular globes or tissue in the orbit since birth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28590501", "endSection": "abstract" } ] }, { "body": "What are the roles of LEM-3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29879106", "http://www.ncbi.nlm.nih.gov/pubmed/29463814", "http://www.ncbi.nlm.nih.gov/pubmed/22383942" ], "ideal_answer": [ "LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis. The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans. LEM-3 is able to process erroneous recombination intermediates that persist into the second meiotic division." ], "exact_answer": [ [ "LEM-3 resolves chromatin bridges during late mitosis" ], [ "LEM-3 is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans" ], [ "LEM-3 is able to process erroneous recombination intermediates that persist into the second meiotic division." ] ], "type": "list", "id": "5c54224807647bbc4b000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29463814", "endSection": "title" }, { "offsetInBeginSection": 149, "offsetInEndSection": 1086, "text": "Using C. elegans embryos we show that the LEM-3/Ankle1 nuclease defines a previously undescribed genome integrity mechanism by processing DNA bridges right before cells divide. LEM-3 acts at the midbody, the structure where abscission occurs at the end of cytokinesis. LEM-3 localization depends on factors needed for midbody assembly, and LEM-3 accumulation is increased and prolonged when chromatin bridges are trapped at the cleavage plane. LEM-3 locally processes chromatin bridges that arise from incomplete DNA replication, unresolved recombination intermediates, or the perturbance of chromosome structure. Proper LEM-3 midbody localization and function is regulated by AIR-2/Aurora B kinase. Strikingly, LEM-3 acts cooperatively with the BRC-1/BRCA1 homologous recombination factor to promote genome integrity. These findings provide a molecular basis for the suspected role of the LEM-3 orthologue Ankle1 in human breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29463814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29879106", "endSection": "title" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1953, "text": "Here we show that the LEM-3 nuclease, mutation of which by itself does not have an overt meiotic phenotype, genetically interacts with slx-1 and mus-81 mutants, the respective double mutants displaying 100% embryonic lethality. The combined loss of LEM-3 and MUS-81 leads to altered processing of recombination intermediates, a delayed disassembly of foci associated with CO designated sites, and the formation of univalents linked by SPO-11 dependent chromatin bridges (dissociated bivalents). However, LEM-3 foci do not colocalize with ZHP-3, a marker that congresses into CO designated sites. In addition, neither CO frequency nor distribution is altered in lem-3 single mutants or in combination with mus-81 or slx-4 mutations. Finally, we found persistent chromatin bridges during meiotic divisions in lem-3; slx-4 double mutants. Supported by the localization of LEM-3 between dividing meiotic nuclei, this data suggest that LEM-3 is able to process erroneous recombination intermediates that persist into the second meiotic division.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29879106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "LEM-3 - A LEM domain containing nuclease involved in the DNA damage response in C. elegans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383942", "endSection": "title" }, { "offsetInBeginSection": 849, "offsetInEndSection": 967, "text": "Strikingly, LEM-3 acts cooperatively with the BRC-1/BRCA1 homologous recombination factor to promote genome integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29463814", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 762, "text": "LEM-3 locally processes chromatin bridges that arise from incomplete DNA replication, unresolved recombination intermediates, or the perturbance of chromosome structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29463814", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 325, "text": "Using C. elegans embryos we show that the LEM-3/Ankle1 nuclease defines a previously undescribed genome integrity mechanism by processing DNA bridges right before cells divide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29463814", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 417, "text": "LEM-3 acts at the midbody, the structure where abscission occurs at the end of cytokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29463814", "endSection": "abstract" } ] }, { "body": "What is the contribution of ultraconserved elements in Australasian smurf-weevils?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29166661" ], "ideal_answer": [ "Ultraconserved elements (UCEs) resolve the phylogeny of Australasian smurf-weevils." ], "type": "summary", "id": "5c52c8b07e3cb0e23100000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Ultraconserved elements (UCEs) resolve the phylogeny of Australasian smurf-weevils.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166661", "endSection": "title" }, { "offsetInBeginSection": 300, "offsetInEndSection": 1460, "text": "Here, we employ ultraconserved elements (UCEs) designed for beetles and a novel partitioning strategy of loci to help resolve phylogenetic relationships within the radiation of Australasian smurf-weevils (Eupholini). Despite being emblematic of the New Guinea fauna, no previous phylogenetic studies have been conducted on the Eupholini. In addition to a comprehensive collection of fresh specimens, we supplement our taxon sampling with museum specimens, and this study is the first target enrichment phylogenomic dataset incorporating beetle specimens from museum collections. We use both concatenated and species tree analyses to examine the relationships and taxonomy of this group. For species tree analyses we present a novel partitioning strategy to better model the molecular evolutionary process in UCEs. We found that the current taxonomy is problematic, largely grouping species on the basis of similar color patterns. Finally, our results show that most loci required multiple partitions for nucleotide rate substitution, suggesting that single partitions may not be the optimal partitioning strategy to accommodate rate heterogeneity for UCE loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Ultraconserved elements (UCEs) resolve the phylogeny of Australasian smurf-weevils.Weevils (Curculionoidea) comprise one of the most diverse groups of organisms on earth. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166661", "endSection": "title" }, { "offsetInBeginSection": 300, "offsetInEndSection": 516, "text": "Here, we employ ultraconserved elements (UCEs) designed for beetles and a novel partitioning strategy of loci to help resolve phylogenetic relationships within the radiation of Australasian smurf-weevils (Eupholini).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29166661", "endSection": "abstract" } ] }, { "body": "How does botulism toxin act on the muscle?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9339823", "http://www.ncbi.nlm.nih.gov/pubmed/1311751", "http://www.ncbi.nlm.nih.gov/pubmed/14747968", "http://www.ncbi.nlm.nih.gov/pubmed/28569348", "http://www.ncbi.nlm.nih.gov/pubmed/20178376" ], "ideal_answer": [ ". The seven immunologically distinct serotypes of BoNTs (A-G), each produced by various strains of Clostridium botulinum, act on the neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis.", "Botulinum toxin (BTX) is widely used to treat muscle spasticity by acting on motor neurons producing a flaccid paralysis. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction." ], "type": "summary", "id": "5c54d00e07647bbc4b000005", "snippets": [ { "offsetInBeginSection": 118, "offsetInEndSection": 384, "text": ". The seven immunologically distinct serotypes of BoNTs (A-G), each produced by various strains of Clostridium botulinum, act on the neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20178376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "Botulinum toxins, exotoxins of Clostridium botulinum, are the most toxic naturally occurring substances known to man. For more than a century they are known to be the cause of botulism, a nowadays rare intoxication with spoiled food that leads to generalized flaccid weakness of striated muscle including pharyngeal and respiratory musculature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9339823", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "The neurotoxins produced by Clostridium botulinum are the most potent acute toxins known and are the causative agents of the neuroparalytic disease botulism. The toxins act primarily at peripheral cholinergic synapses by blocking the evoked release of the neurotransmitter acetylcholine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1311751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "BACKGROUND\nBotulism is a rare potentially fatal and treatable disorder caused by a bacteria-produced toxin that affects the presynaptic synaptic membrane resulting in a characteristic neuromuscular dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28569348", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 827, "text": "The toxin irreversibly blocks the release of acetylcholin from the motoric end plate which results in muscle weakness and paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14747968", "endSection": "abstract" } ] }, { "body": "What is the most common pediatric glioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29241176", "http://www.ncbi.nlm.nih.gov/pubmed/29568396", "http://www.ncbi.nlm.nih.gov/pubmed/29569086", "http://www.ncbi.nlm.nih.gov/pubmed/28830841", "http://www.ncbi.nlm.nih.gov/pubmed/29204019", "http://www.ncbi.nlm.nih.gov/pubmed/29548059", "http://www.ncbi.nlm.nih.gov/pubmed/29170066" ], "ideal_answer": [ "Pilocytic astrocytoma is the most common pediatric glioma." ], "exact_answer": [ "Pilocytic astrocytoma or high grade glioma" ], "type": "factoid", "id": "5c6bec987c78d69471000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "High-grade gliomas (HGG) are the most common malignant brain tumors in the pediatric population and account for a large subset of all pediatric central nervous system neoplasms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28830841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Gliomas are the most common type of brain cancer in the pediatric patients, constituting about 50% of all childhood intracranial tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29241176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Gliomas are the most common malignant primary brain tumors, of which glioblastoma is the most malignant form (WHO grade IV), and notorious for treatment resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29170066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and occurs in different locations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29548059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Pilocytic astrocytomas (PAs) are benign glial tumors and one of the most common childhood posterior fossa tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29569086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "High-grade gliomas (HGG) are the most common malignant brain tumors in the pediatric population and account for a large subset of all pediatric central nervous system neoplasms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28830841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and occurs in different locations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568396", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1309, "text": "Medulloblastoma, glioma, and craniopharyngioma were the most common pediatric tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29204019", "endSection": "abstract" } ] }, { "body": "What is the function of the protein encoded by the gene STING?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29346345", "http://www.ncbi.nlm.nih.gov/pubmed/28748479", "http://www.ncbi.nlm.nih.gov/pubmed/29367762" ], "ideal_answer": [ "Stimulator of interferon genes (STING) is an adaptor protein that plays an important role in the activation of type I interferons in response to cytosolic nucleic acid ligands. Recent evidence indicates involvement of the STING pathway in the induction of antitumor immune response." ], "exact_answer": [ "activation of type I interferons" ], "type": "factoid", "id": "5c7aae9dd774d0424000000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Stimulator of interferon genes (STING) is an adaptor protein that plays an important role in the activation of type I interferons in response to cytosolic nucleic acid ligands. Recent evidence indicates involvement of the STING pathway in the induction of antitumor immune response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29346345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "The production of cytokines in response to DNA-damage events may be an important host defense response to help prevent the escape of pre-cancerous cells. The innate immune pathways involved in these events are known to be regulated by cellular molecules such as stimulator of interferon genes (STING), which controls type I interferon and pro-inflammatory cytokine production in response to the presence of microbial DNA or cytosolic DNA that has escaped from the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29367762", "endSection": "abstract" } ] }, { "body": "List uniparental disomy (UPD) detection algorithms", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17564968", "http://www.ncbi.nlm.nih.gov/pubmed/23589652" ], "ideal_answer": [ "UPDtool and AsCNAR are tools for detecting uniparental disomy (UPD). UPDtool is a computational tool for detection and classification of uniparental disomy (UPD) in trio SNP-microarray experiments. AsCNAR (allele-specific copy-number analysis using anonymous references) detects the copy-number neutral LOH, or uniparental disomy (UPD), in a large number of acute leukemia samples." ], "exact_answer": [ [ "UPDtool" ], [ "AsCNAR (allele-specific copy-number analysis using anonymous references)" ] ], "type": "list", "id": "5c544c1707647bbc4b000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "UPDtool: a tool for detection of iso- and heterodisomy in parent-child trios using SNP microarrays.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23589652", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "UPDtool is a computational tool for detection and classification of uniparental disomy (UPD) in trio SNP-microarray experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23589652", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1699, "text": "The performance of the new algorithm, called \"AsCNAR\" (allele-specific copy-number analysis using anonymous references), was demonstrated by detecting the copy-number neutral LOH, or uniparental disomy (UPD), in a large number of acute leukemia samples. We next applied this technique to detection of UPD involving the 9p arm in myeloproliferative disorders (MPDs), which is tightly associated with a homozygous JAK2 mutation. It revealed an unexpectedly high frequency of 9p UPD that otherwise would have been undetected and also disclosed the existence of multiple subpopulations having distinct 9p UPD within the same MPD specimen. In conclusion, AsCNAR should substantially improve our ability to dissect the complexity of cancer genomes and should contribute to our understanding of the genetic basis of human cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17564968", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1223, "text": "Our results were compared with both the gold standard, microsatellite analysis and SNPtrio, another program available for UPD detection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23589652", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1204, "text": "Our results were compared with both the gold standard, microsatellite analysis and SNPtrio, another program available for UPD detection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23589652", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of apalutamide.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28636139", "http://www.ncbi.nlm.nih.gov/pubmed/29381490", "http://www.ncbi.nlm.nih.gov/pubmed/30426794", "http://www.ncbi.nlm.nih.gov/pubmed/29606109", "http://www.ncbi.nlm.nih.gov/pubmed/29420164", "http://www.ncbi.nlm.nih.gov/pubmed/29856649", "http://www.ncbi.nlm.nih.gov/pubmed/29695920", "http://www.ncbi.nlm.nih.gov/pubmed/29734647", "http://www.ncbi.nlm.nih.gov/pubmed/29626324", "http://www.ncbi.nlm.nih.gov/pubmed/27160947" ], "ideal_answer": [ "Apalutamide is a second-generation antiandrogen that inhibits the binding of androgen to androgen receptor (AR), nuclear translocation of the androgen-AR complex, and binding of AR transcription complex to DNA-binding sites and transcription elements. It does not show antagonist-to-agonist switch like bicalutamide. It is emerging as additional new option to treat castration-resistant prostate cancer." ], "type": "summary", "id": "5c6dfba77c78d69471000046", "snippets": [ { "offsetInBeginSection": 440, "offsetInEndSection": 614, "text": "Second-generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28636139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "BACKGROUND: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29420164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29381490", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 415, "text": "Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606109", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 750, "text": "Apalutamide (ARN-509), a second-generation androgen receptor antagonist, recently received approval in the nonmetastatic (M0) CRPC space. Similar to enzalutamide, apalutamide inhibits the binding of androgen to androgen receptor (AR), nuclear translocation of the androgen-AR complex, and binding of AR transcription complex to DNA-binding sites and transcription elements. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29695920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Apalutamide (ErleadaTM) is a next-generation oral androgen receptor (AR) inhibitor that is being developed by Janssen for the treatment of prostate cancer (PC). It binds directly to the ligand-binding domain of the AR and blocks the effects of androgens. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29626324", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 1079, "text": "Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29734647", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 502, "text": " One of these agents is apalutamide, which seems to be a promising AR antagonist for the treatment of CRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856649", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 921, "text": "Expert opinion: Apalutamide is an oral, investigational, AR antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27160947", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "BACKGROUND\nApalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27160947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "BACKGROUND\nApalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29420164", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 414, "text": "Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606109", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 749, "text": "Similar to enzalutamide, apalutamide inhibits the binding of androgen to androgen receptor (AR), nuclear translocation of the androgen-AR complex, and binding of AR transcription complex to DNA-binding sites and transcription elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29695920", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 513, "text": "Apalutamide (ARN-509), a second-generation androgen receptor antagonist, recently received approval in the nonmetastatic (M0) CRPC space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29695920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Apalutamide (ErleadaTM) is a next-generation oral androgen receptor (AR) inhibitor that is being developed by Janssen for the treatment of prostate cancer (PC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29626324", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 907, "text": "Expert opinion: Apalutamide is an oral, investigational, AR antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856649", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 349, "text": "Apalutamide, an androgen receptor inhibitor, has substantial clinical response in nonmetastatic castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30426794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "BACKGROUND Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27160947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "BACKGROUND Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29420164", "endSection": "abstract" } ] }, { "body": "Which molecule is inhibited by larotrectinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30069765", "http://www.ncbi.nlm.nih.gov/pubmed/29466156", "http://www.ncbi.nlm.nih.gov/pubmed/29568395", "http://www.ncbi.nlm.nih.gov/pubmed/29653952", "http://www.ncbi.nlm.nih.gov/pubmed/30204247", "http://www.ncbi.nlm.nih.gov/pubmed/28578312", "http://www.ncbi.nlm.nih.gov/pubmed/30350734", "http://www.ncbi.nlm.nih.gov/pubmed/29606586", "http://www.ncbi.nlm.nih.gov/pubmed/29764494" ], "ideal_answer": [ "Larotrectinib is oral, potent, and selective inhibitor of tropomyosin receptor kinases (TRK). It demonstrated unprecedented efficacy on unresectable or metastatic solid tumors with neurotrophic tropomyosin receptor kinase (NTRK)-fusion proteins in adult and pediatric patients." ], "exact_answer": [ "tropomyosin receptor kinases" ], "type": "factoid", "id": "5c6e0f537c78d6947100004a", "snippets": [ { "offsetInBeginSection": 127, "offsetInEndSection": 273, "text": "We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29466156", "endSection": "abstract" }, { "offsetInBeginSection": 1760, "offsetInEndSection": 1932, "text": "CONCLUSIONS: Larotrectinib had marked and durable antitumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or of the tumor type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29466156", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 307, "text": "Larotrectinib, a highly selective small-molecule inhibitor of the TRK kinases, had shown activity in preclinical models and in adults with tumours harbouring TRK fusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606586", "endSection": "abstract" }, { "offsetInBeginSection": 3890, "offsetInEndSection": 4072, "text": "INTERPRETATION: The TRK inhibitor larotrectinib was well tolerated in paediatric patients and showed encouraging antitumour activity in all patients with TRK fusion-positive tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606586", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1347, "text": "In the 2017 American Society for Clinical Oncology annual meeting, larotrectinib (LOXO-101), Loxooncology's oral, potent, and selective inhibitor of tropomyosin receptor kinases (TRK), demonstrated unprecedented efficacy on unresectable or metastatic solid tumors with neurotrophic tropomyosin receptor kinase (NTRK)-fusion proteins in adult and pediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29764494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Larotrectinib Has Antitumor Activity in TRK", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29653952", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Larotrectinib achieved a 93% response rate in pediatric patients with TRK fusion-positive tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29653952", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 995, "text": "To recapitulate resistance observed from type I NTRK kinase inhibitors entrectinib and larotrectinib, we generated NIH-3T3 cells exogenously expressing TPM3-NTRK1 wild-type, or acquired mutations G595R and G667C in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568395", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 398, "text": "Larotrectinib is the first highly potent and selective small molecule ATP competitive inhibitor of all three TRK kinases to enter clinical development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30350734", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 339, "text": "Larotrectinib is the first highly potent and selective small molecule ATP competitive inhibitor of all three TRK kinases to enter clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30350734", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 489, "text": "Areas covered: This review covers the current preclinical and clinical evidence for TRK inhibitors for TRK fusion cancers, focusing on larotrectinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30350734", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 306, "text": "Larotrectinib, a highly selective small-molecule inhibitor of the TRK kinases, had shown activity in preclinical models and in adults with tumours harbouring TRK fusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "BACKGROUND\nThe highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204247", "endSection": "abstract" }, { "offsetInBeginSection": 3896, "offsetInEndSection": 4077, "text": "INTERPRETATION\nThe TRK inhibitor larotrectinib was well tolerated in paediatric patients and showed encouraging antitumour activity in all patients with TRK fusion-positive tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606586", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1432, "text": "Several TRK inhibitors have been developed, and one of them, Larotrectinib (formerly known as LOXO-101), represents an orally available, selective inhibitor of the TRK receptor family that has already shown substantial clinical benefit in both pediatric and adult patients harboring an NTRK gene fusion over the last few years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30069765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "BACKGROUND The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30204247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Larotrectinib, a selective TRK tyrosine kinase inhibitor (TKI), has demonstrated histology-agnostic efficacy in patients with TRK fusion-positive cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28578312", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 510, "text": "Areas covered: This review covers the current preclinical and clinical evidence for TRK inhibitors for TRK fusion cancers, focusing on larotrectinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30350734", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1436, "text": "Several TRK inhibitors have been developed, and one of them, Larotrectinib (formerly known as LOXO-101), represents an orally available, selective inhibitor of the TRK receptor family that has already shown substantial clinical benefit in both pediatric and adult patients harboring an NTRK gene fusion over the last few years.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30069765", "endSection": "abstract" } ] }, { "body": "What is Bayesian haplotyping used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29358597", "http://www.ncbi.nlm.nih.gov/pubmed/28123903" ], "ideal_answer": [ "Bayesian haplotype inference is used for phylogenetic analysis, specifcially multiple linked single-nucleotide polymorphisms and analysis of chromosome copy number and deletions." ], "type": "summary", "id": "5c6bedd57c78d69471000034", "snippets": [ { "offsetInBeginSection": 474, "offsetInEndSection": 695, "text": " We employed Bayesian Inference (BI) methods for the phylogenetic reconstructions and divergence dating among lineages, using unique haplotype sequences from two mitochondrial loci (COXI, 16S) and one nuclear locus (28S).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28123903", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 842, "text": "Phylogenetic analyses of mitogenome sequences by maximum likelihood (ML) and Bayesian inference identified a monophyletic RSA clade, subdivided into two clades.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358597", "endSection": "abstract" } ] }, { "body": "List major features of TEMPI Syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25216227", "http://www.ncbi.nlm.nih.gov/pubmed/27501129", "http://www.ncbi.nlm.nih.gov/pubmed/25143825", "http://www.ncbi.nlm.nih.gov/pubmed/25911963", "http://www.ncbi.nlm.nih.gov/pubmed/30100329" ], "ideal_answer": [ "TEMPI syndrome includes telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting. It is a newly described clinical entity that is generally considered a plasma cell dyscrasia with multiple system involvement." ], "exact_answer": [ [ "telangiectasias" ], [ "erythrocytosis with elevated erythropoietin" ], [ "monoclonal gammopathy" ], [ "perinephric fluid collections" ], [ "intrapulmonary shunting" ] ], "type": "list", "id": "5c6b7daa7c78d6947100002b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "TEMPI Syndrome: Erythrocytosis in Plasma Cell Dyscrasia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30100329", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "TEMPI (telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting) syndrome is a newly described clinical entity that is generally considered a plasma cell dyscrasia with multiple system involvement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30100329", "endSection": "abstract" }, { "offsetInBeginSection": 1695, "offsetInEndSection": 1920, "text": "In other MGCS, such as scleromyxedema, Clarkson syndrome, TEMPI syndrome, cutis laxa and the neutrophilic dermatoses, the link between the monoclocal component and the entity is clearly established, but not understood so far.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27501129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a recently described syndrome that, owing to erythrocytosis, may be confused with polycythemia vera.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216227", "endSection": "abstract" }, { "offsetInBeginSection": 1592, "offsetInEndSection": 1697, "text": "In conclusion, TEMPI syndrome should be considered when erythrocytosis and plasma cell dyscrasia coexist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "BACKGROUND\nThe TEMPI syndrome was recently described in 2011, and is characterized by the constellation of five hallmarks: Telangiectasias, Erythrocytosis and elevated Erythropoietin, Monoclonal gammopathy, Perinephric fluids collections, and Intrapulmonary shunting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25143825", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 438, "text": "TEMPI syndrome is a recently described condition defined by teleangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25911963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "BACKGROUND The TEMPI syndrome was recently described in 2011, and is characterized by the constellation of five hallmarks: Telangiectasias, Erythrocytosis and elevated Erythropoietin, Monoclonal gammopathy, Perinephric fluids collections, and Intrapulmonary shunting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25143825", "endSection": "abstract" } ] }, { "body": "Describe Herpetic Whitlow.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28376707", "http://www.ncbi.nlm.nih.gov/pubmed/11585074", "http://www.ncbi.nlm.nih.gov/pubmed/26001830", "http://www.ncbi.nlm.nih.gov/pubmed/2933494", "http://www.ncbi.nlm.nih.gov/pubmed/28065641", "http://www.ncbi.nlm.nih.gov/pubmed/25436164", "http://www.ncbi.nlm.nih.gov/pubmed/8362051", "http://www.ncbi.nlm.nih.gov/pubmed/11921024", "http://www.ncbi.nlm.nih.gov/pubmed/17674583" ], "ideal_answer": [ "Herpetic whitlow is an acute viral infection of the hand caused by either herpes simplex virus (HSV) 1 or 2. Its characteristic findings are significant pain and erythema with overlying nonpurulent vesicles. It can be confirmed by polymerase chain reaction testing." ], "type": "summary", "id": "5c6e12247c78d6947100004b", "snippets": [ { "offsetInBeginSection": 270, "offsetInEndSection": 497, "text": "Superficial hand infections are located superficial to the tendons and are comprised of cellulitis, lymphangitis, paronychia, pulp-space infections, herpetic whitlow, and include volar as well as dorsal subcutaneous abscesses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28065641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "CONTEXT: Herpetic whitlow is caused by herpes virus (type1 or 2) during primary infection or as result of autoinoculation. Commonly, it is caused by HSV-2 in adults with positive history for genital infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28376707", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 704, "text": "CONCLUSION: The case here reported demonstrates that herpetic whitlow should be kept in mind by physicians in recurrent cases of fingers infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28376707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "INTRODUCTION: Whitlow is an infection of a finger or around the fingernails, generally caused by bacterium. However, in rare cases, it may also be caused by the herpes simplex virus. As herpetic whitlow is not seen often, it may go under-recognised or be mistaken for a different kind of infection of the finger. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26001830", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 960, "text": "He had multiple vesicles on the finger, which led to the diagnosis of herpetic whitlow, which we confirmed by polymerase chain reaction testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26001830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Herpetic whitlow is an acute viral infection of the hand caused by either herpes simplex virus (HSV) 1 or 2. Its characteristic findings are significant pain and erythema with overlying nonpurulent vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Herpetic whitlow, a herpes simplex virus infection involving the digits, most commonly presents as a vesicular eruption involving a single digit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11921024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Herpetic whitlow is a herpes simplex virus infection of the finger.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2933494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Herpetic whitlow is a painful cutaneous infection that most commonly affects the distal phalanx of the fingers and occasionally the toes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17674583", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 857, "text": "Herpetic whitlow may have a prodrome of burning, pruritus, and/or tingling of the affected finger or the entire limb, followed by erythema, pain, and vesicle formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17674583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "UNLABELLED\nHerpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers characterised by erythema and painful, non-purulent vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11585074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "This paper describes a case of transmission of herpetic whitlow to the index finger of a dental student from a patient with herpes simplex virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8362051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "UNLABELLED Herpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers characterised by erythema and painful, non-purulent vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11585074", "endSection": "abstract" } ] }, { "body": "Sweat Chloride Testing is used for which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29580829", "http://www.ncbi.nlm.nih.gov/pubmed/28193033", "http://www.ncbi.nlm.nih.gov/pubmed/28194692", "http://www.ncbi.nlm.nih.gov/pubmed/28852705", "http://www.ncbi.nlm.nih.gov/pubmed/17405070", "http://www.ncbi.nlm.nih.gov/pubmed/23605131", "http://www.ncbi.nlm.nih.gov/pubmed/23056867", "http://www.ncbi.nlm.nih.gov/pubmed/29436379", "http://www.ncbi.nlm.nih.gov/pubmed/18728376", "http://www.ncbi.nlm.nih.gov/pubmed/25530017", "http://www.ncbi.nlm.nih.gov/pubmed/24485874", "http://www.ncbi.nlm.nih.gov/pubmed/15274098", "http://www.ncbi.nlm.nih.gov/pubmed/29124052", "http://www.ncbi.nlm.nih.gov/pubmed/28208841", "http://www.ncbi.nlm.nih.gov/pubmed/28129813", "http://www.ncbi.nlm.nih.gov/pubmed/29338740" ], "ideal_answer": [ "Sweat Chloride Testing is used to diagnose cystic fibrosis. CFTR dysfunction can be demonstrated using sweat chloride testing." ], "exact_answer": [ "cystic fibrosis" ], "type": "factoid", "id": "5c6e16eb7c78d6947100004e", "snippets": [ { "offsetInBeginSection": 1178, "offsetInEndSection": 1380, "text": "Screen-positive newborns and patients with high clinical suspicion for CF are always recommended to undergo confirmatory sweat chloride testing with interpretations based on updated reference intervals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29436379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "BACKGROUND: Sweat chloride testing for diagnosis of cystic fibrosis (CF) involves sweat induction, collection and handling, and measurement in an analytical lab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29580829", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1487, "text": "CFTR dysfunction can be demonstrated using sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28129813", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1299, "text": "In eighty-three patients (26.4%) CFTR mutational analysis was done without corresponding sweat chloride testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28194692", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 581, "text": "Herein we report the first characterization of the sweat metabolome from screen-positive CF infants and identify metabolites associated with disease status that complement sweat chloride testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Objective: To conduct a descriptive analysis of the sweat test (ST), associating ST results with epidemiological data, CFTR (cystic fibrosis transmembrane conductance regulator) mutations and reasons to indicate the ST, as well as correlating sweat sodium and sweat chloride concentrations in subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124052", "endSection": "abstract" }, { "offsetInBeginSection": 1956, "offsetInEndSection": 2117, "text": "Conclusions: ST data showed wide variability dependent on age, sex, reason for examination indication, CFTR mutations, and weight of the collected sweat sample. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124052", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 356, "text": "Sweat testing is a gold standard for diagnosis of CF patients as genetic mutation profile being heterozygous and unlikely to become diagnostic test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28208841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport.The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support of universal newborn screening programs. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852705", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Assessment of Correlation between Sweat Chloride Levels and Clinical Features of Cystic Fibrosis Patients.The diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28208841", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 384, "text": "However, it provides ambiguous results for intermediate sweat chloride cases while not reflecting disease progression when classifying the complex CF disease spectrum given the pleiotropic effects of gene modifiers and environment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "In cystic fibrosis (CF), sweat chloride concentration has been proposed as an index of CFTR function for testing systemic drugs designed to activate mutant CFTR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15274098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND\nSweat chloride testing for diagnosis of cystic fibrosis (CF) involves sweat induction, collection and handling, and measurement in an analytical lab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29580829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "OBJECTIVES\nSweat chloride testing is the gold standard for diagnosis of cystic fibrosis (CF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25530017", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 298, "text": "The distinguishable salty character of the sweat belonging to individuals suffering from CF makes sweat chloride estimation essential for diagnosis of CF disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28208841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support of universal newborn screening programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852705", "endSection": "abstract" }, { "offsetInBeginSection": 1828, "offsetInEndSection": 1976, "text": "Sweat testing is a gold standard for diagnosis of CF patients as genetic mutation profile being heterozygous and unlikely to become diagnostic test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28208841", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 247, "text": "Sweat chloride is of interest as a biomarker for cystic fibrosis, electrolyte metabolism disorders, electrolyte balance, and electrolyte loss during exercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28193033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "OBJECTIVES Sweat chloride testing is the gold standard for diagnosis of cystic fibrosis (CF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25530017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND Sweat chloride testing for diagnosis of cystic fibrosis (CF) involves sweat induction, collection and handling, and measurement in an analytical lab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29580829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "BACKGROUND Sweat chloride test is the gold standard test for cystic fibrosis (CF) diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24485874", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 325, "text": "Sweat chloride test is known to be a screening test for the cystic fibrosis due to the fact that electrolyte levels in sweat are elevated in patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18728376", "endSection": "abstract" }, { "offsetInBeginSection": 1836, "offsetInEndSection": 2005, "text": "CONCLUSIONS Sweat chloride concentrations were within the normal range in patients with DS and therefore seem to be a reliable tool for testing for CF in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29338740", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "OBJECTIVE Sweat chloride measurement is considered a standard diagnostic tool for cystic fibrosis (CF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23056867", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 792, "text": "Patients with CF have raised concentrations of chloride and sodium in their sweat; however, it is the concentration of chloride in sweat which provides the greatest diagnostic sensitivity for CF.
METHOD: An inductively coupled plasma mass spectrometry (ICP-MS) method for the analysis of sweat chloride and sodium was evaluated for the routine measurement of sweat collected using the Wescor Macroduct(\u00ae) Sweat Collection System.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23605131", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 352, "text": "Due to the large number of mutations that can result in classical or atypical CF phenotype, the sweat test, which quantifies the amount of chloride and sodium in sweat, is vital in supporting the diagnosis of CF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23605131", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 619, "text": "The distinguishable salty character of the sweat belonging to individuals suffering from CF makes sweat chloride estimation essential for diagnosis of CF disease.
AIM: The aim of this prospective study was to elucidate the relationship of sweat chloride levels with clinical features and pattern of CF.
MATERIALS AND METHODS: A total of 182 patients, with clinical features of CF were included in this study for quantitative measurement of sweat chloride.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28208841", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 285, "text": "The distinguishable salty character of the sweat belonging to individuals suffering from CF makes sweat chloride estimation essential for diagnosis of CF disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28208841", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 529, "text": "Patients with CF have raised concentrations of chloride and sodium in their sweat; however, it is the concentration of chloride in sweat which provides the greatest diagnostic sensitivity for CF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23605131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Sweat chloride testing for diagnosis of cystic fibrosis (CF) involves sweat induction, collection and handling, and measurement in an analytical lab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29580829", "endSection": "abstract" } ] }, { "body": "What is nyctinasty in plants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17304541", "http://www.ncbi.nlm.nih.gov/pubmed/14527150", "http://www.ncbi.nlm.nih.gov/pubmed/29983317", "http://www.ncbi.nlm.nih.gov/pubmed/29998471", "http://www.ncbi.nlm.nih.gov/pubmed/20349506" ], "ideal_answer": [ "Nyctinasty is the circadian rhythmic nastic movement of leguminous plants in response to the onset of darkness; a unique and intriguing phenomenon that has attracted attention for centuries.", "Leguminous plants open their leaves during the daytime and close them at night as if sleeping, a type of movement that follows circadian rhythms, and is known as nyctinastic movement" ], "exact_answer": [ "movement of leguminous plants in response to darkness" ], "type": "factoid", "id": "5c54d1a207647bbc4b000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Leguminous plants open their leaves during the daytime and close them at night as if sleeping, a type of movement that follows circadian rhythms, and is known as nyctinastic movement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20349506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The chemical aspects of the circadian leaf movement known as \"nyctinasty\" are discussed in this paper.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17304541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Periodic leaf-movement of legumes is called nyctinasty and has been known since the age of Alexander the Great. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14527150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Foliar nyctinasty is a plant behaviour characterised by a pronounced daily oscillation in leaf orientation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29998471", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 264, "text": "We found that nyctinasty is controlled by a periodic change of the internal concentration of leaf-opening and leaf-closing substances in the plant body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14527150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The circadian leaf opening and closing (nyctinasty) of Fabaceae has attracted scientists' attention since the era of Charles Darwin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29983317", "endSection": "abstract" } ] }, { "body": "Does Eucommia ulmoides leaf extract ameliorates steatosis/fatty liver induced by high-fat diet?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18306452", "http://www.ncbi.nlm.nih.gov/pubmed/20691136", "http://www.ncbi.nlm.nih.gov/pubmed/24349058", "http://www.ncbi.nlm.nih.gov/pubmed/28100919" ], "ideal_answer": [ "Yes, Eucommia ulmoides leaf extract can ameliorate steatosis induced by high-fat diet." ], "exact_answer": "yes", "type": "yesno", "id": "5c6d441d7c78d69471000037", "snippets": [ { "offsetInBeginSection": 1236, "offsetInEndSection": 1481, "text": "These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18306452", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1372, "text": " Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24349058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "Du-zhong (Eucommia ulmoides Oliver) leaf extract mediates hypolipidemic action in hamsters fed a high-fat diet.This study examined the effect of a Du-zhong (Eucommia ulmoides Oliver) leaf extract (0.175 g/100 g diet) that was supplemented with a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) on hyperlipidemic hamsters. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18306452", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet.Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28100919", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28100919", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1075, "text": "The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18306452", "endSection": "abstract" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1485, "text": "These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18306452", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 612, "text": "Both forms of Eucommia leaves minimised increases in body weight and visceral fat in a dose-dependent fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691136", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1490, "text": "These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18306452", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1081, "text": "The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18306452", "endSection": "abstract" } ] }, { "body": "List the releases of tmVar", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28968638", "http://www.ncbi.nlm.nih.gov/pubmed/23564842" ], "ideal_answer": [ "TmVar is a text mining approach for extracting sequence variants in biomedical literature. TmVar 2.0 integrates genomic variant information from literature with dbSNP and ClinVar for precision medicine." ], "exact_answer": [ [ "TmVar" ], [ "TmVar 2.0" ] ], "type": "list", "id": "5c561da707647bbc4b00000f", "snippets": [ { "offsetInBeginSection": 702, "offsetInEndSection": 1409, "text": "Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society. By doing so, we cover several important types of mutations that were not considered in past studies. Using a novel CRF label model and feature set, our method achieves higher performance than a state-of-the-art method on both our corpus (91.4 versus 78.1% in F-measure) and their own gold standard (93.9 versus 89.4% in F-measure). These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "tmVar 2.0: integrating genomic variant information from literature with dbSNP and ClinVar for precision medicine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968638", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "tmVar: a text mining approach for extracting sequence variants in biomedical literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "title" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1850, "text": "To our knowledge, this is the first large-scale study to analyze and integrate text-mined variant data with curated knowledge in existing databases. Our results suggest that databases can be significantly enriched by text mining and that the combined information can greatly assist human efforts in evaluating/prioritizing variants in genomic research.Availability and implementation: The tmVar 2.0 source code and corpus are freely available at https://www.ncbi.nlm.nih.gov/research/bionlp/Tools/tmvar/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968638", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 964, "text": "RESULTS\nHere, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1410, "text": "These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1572, "text": "AVAILABILITY\ntmVar software and its corpus of 500 manually curated abstracts are available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/pub/tmVar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 1854, "text": "Availability and implementation\nThe tmVar 2.0 source code and corpus are freely available at https://www.ncbi.nlm.nih.gov/research/bionlp/Tools/tmvar/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968638", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 964, "text": "RESULTS Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1572, "text": "AVAILABILITY tmVar software and its corpus of 500 manually curated abstracts are available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/pub/tmVar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 1854, "text": "Availability and implementation The tmVar 2.0 source code and corpus are freely available at https://www.ncbi.nlm.nih.gov/research/bionlp/Tools/tmvar/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968638", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 981, "text": "As such, new automatic approaches are greatly needed for extracting different kinds of mutations with high accuracy.
RESULTS: Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1602, "text": "These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.
AVAILABILITY: tmVar software and its corpus of 500 manually curated abstracts are available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/pub/tmVar
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1923, "text": "Our results suggest that databases can be significantly enriched by text mining and that the combined information can greatly assist human efforts in evaluating/prioritizing variants in genomic research.
Availability and implementation: The tmVar 2.0 source code and corpus are freely available at https://www.ncbi.nlm.nih.gov/research/bionlp/Tools/tmvar/.
Contact: zhiyong.lu@nih.gov.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968638", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1536, "text": "tmVar software and its corpus of 500 manually curated abstracts are available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/pub/tmVar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1680, "offsetInEndSection": 1799, "text": "The tmVar 2.0 source code and corpus are freely available at https://www.ncbi.nlm.nih.gov/research/bionlp/Tools/tmvar/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968638", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1389, "text": "These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" } ] }, { "body": "Which deep learning algorithm has been developed for variant calling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30247488" ], "ideal_answer": [ "A deep convolutional neural network can call genetic variation in aligned next-generation sequencing read data by learning statistical relationships between images of read pileups around putative variant and true genotype calls. The approach, called DeepVariant, outperforms existing state-of-the-art tools. The learned model generalizes across genome builds and mammalian species, allowing nonhuman sequencing projects to benefit from the wealth of human ground-truth data." ], "exact_answer": [ "DeepVariant" ], "type": "factoid", "id": "5c51fb7a07ef653866000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 978, "text": "Despite rapid advances in sequencing technologies, accurately calling genetic variants present in an individual genome from billions of short, errorful sequence reads remains challenging. Here we show that a deep convolutional neural network can call genetic variation in aligned next-generation sequencing read data by learning statistical relationships between images of read pileups around putative variant and true genotype calls. The approach, called DeepVariant, outperforms existing state-of-the-art tools. The learned model generalizes across genome builds and mammalian species, allowing nonhuman sequencing projects to benefit from the wealth of human ground-truth data. We further show that DeepVariant can learn to call variants in a variety of sequencing technologies and experimental designs, including deep whole genomes from 10X Genomics and Ion Ampliseq exomes, highlighting the benefits of using more automated and generalizable techniques for variant calling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30247488", "endSection": "abstract" } ] }, { "body": "What 2 biological processes are regulated by STAMP2 in adipocytes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29190878", "http://www.ncbi.nlm.nih.gov/pubmed/21849520", "http://www.ncbi.nlm.nih.gov/pubmed/22704678", "http://www.ncbi.nlm.nih.gov/pubmed/18381574", "http://www.ncbi.nlm.nih.gov/pubmed/23874564", "http://www.ncbi.nlm.nih.gov/pubmed/19289123", "http://www.ncbi.nlm.nih.gov/pubmed/17482547" ], "ideal_answer": [ "Inflammation, insulin resistance and metabolic response are regulated by STAMP2 in adipocytes.", "six-transmembrane protein stamp2 as a critical modulator of this integrated response system of inflammation and metabolism" ], "exact_answer": [ [ "metabolic response" ], [ "inflammation" ], [ "insulin resistance" ] ], "type": "list", "id": "5c57041807647bbc4b000015", "snippets": [ { "offsetInBeginSection": 110, "offsetInEndSection": 313, "text": "Recently, we found that Stamp2 has a critical role in the integration of inflammatory and metabolic signals in adipose tissue where it is highly expressed and regulated by nutritional and metabolic cues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23874564", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 543, "text": "we identified the six-transmembrane protein STAMP2 as a critical modulator of this integrated response system of inflammation and metabolism in adipocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17482547", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 135, "text": "Six transmembrane protein of prostate 2 (STAMP2) is a counterregulator of adipose inflammation and insulin resistance in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18381574", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 404, "text": "Recently, we found that Stamp2 has a critical role in the integration of inflammatory and metabolic signals in adipose tissue where it is highly expressed and regulated by nutritional and metabolic cues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23874564", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1321, "text": "These results suggest that Stamp1 and Stamp2 play critical roles in adipogenesis, but through different mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23874564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "CONTEXT\nSix transmembrane protein of prostate 2 (STAMP2) is a counterregulator of adipose inflammation and insulin resistance in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18381574", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 920, "text": "These results suggest that STAMP2 is crucial for normal ASC conversion into adipocytes and their metabolic function, as well as their ability to facilitate PCa growth in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29190878", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 309, "text": "We report that Stamp2 is expressed in human and mouse macrophages, is regulated upon differentiation or activation, acts as an anti-inflammatory protein, and regulates foam cell formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22704678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "CONTEXT Six-transmembrane protein of prostate 2 (STAMP2) is a counter-regulator of inflammation and insulin resistance according to findings in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21849520", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 976, "text": "Taken together, TIARP/STAMP2 is highly upregulated in 3T3-L1 cells and hMSC-Ad by IL-1beta and might, therefore, modulate proinflammatory and insulin resistance-inducing effects of IL-1beta.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "CONTEXT: Six transmembrane protein of prostate 2 (STAMP2) is a counterregulator of adipose inflammation and insulin resistance in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18381574", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 987, "text": "Our hypothesis was that STAMP2 could be involved in human obesity and insulin resistance.
OBJECTIVE: The objective of the study was to elucidate the role of adipose STAMP2 expression in human obesity and insulin resistance.
DESIGN: The design was to quantify STAMP2 in human abdominal sc and omental white adipose tissue (WAT), isolated adipocytes, and stroma and in vitro differentiated preadipocytes and relate levels of STAMP2 in sc WAT to clinical and adipocyte phenotypes involved in insulin resistance.
PARTICIPANTS: Nonobese and obese women and men (n = 236) recruited from an obesity clinic or through local advertisement.
MAIN OUTCOME MEASUREMENT: Clinical measures included body mass index, body fat, total adiponectin, and homeostasis model assessment as measure of overall insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18381574", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 972, "text": "Taken together, TIARP/STAMP2 is highly upregulated in 3T3-L1 cells and hMSC-Ad by IL-1beta and might, therefore, modulate proinflammatory and insulin resistance-inducing effects of IL-1beta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19289123", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Pitolisant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27568835", "http://www.ncbi.nlm.nih.gov/pubmed/27438291", "http://www.ncbi.nlm.nih.gov/pubmed/27223666", "http://www.ncbi.nlm.nih.gov/pubmed/29075190", "http://www.ncbi.nlm.nih.gov/pubmed/29802412", "http://www.ncbi.nlm.nih.gov/pubmed/27787717", "http://www.ncbi.nlm.nih.gov/pubmed/28129985", "http://www.ncbi.nlm.nih.gov/pubmed/22820944", "http://www.ncbi.nlm.nih.gov/pubmed/30359639", "http://www.ncbi.nlm.nih.gov/pubmed/28490912", "http://www.ncbi.nlm.nih.gov/pubmed/23472741", "http://www.ncbi.nlm.nih.gov/pubmed/22356925", "http://www.ncbi.nlm.nih.gov/pubmed/24107292", "http://www.ncbi.nlm.nih.gov/pubmed/23327739", "http://www.ncbi.nlm.nih.gov/pubmed/28449891", "http://www.ncbi.nlm.nih.gov/pubmed/30503715" ], "ideal_answer": [ "Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor thus increasing histaminergic tone in the wake promoting system of the brain. It is used for the treatment of narcolepsy." ], "type": "summary", "id": "5c6f0ebf7c78d69471000050", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1120, "text": "The histamine H3 receptor is a G protein-coupled receptor (GPCR) drug target that is highly expressed in the CNS, where it acts as both an auto- and hetero-receptor to regulate neurotransmission. As such, it has been considered as a relevant target in disorders as varied as Alzheimer's disease, schizophrenia, neuropathic pain and attention deficit hyperactivity disorder. A range of competitive antagonists/inverse agonists have progressed into clinical development, with pitolisant approved for the treatment of narcolepsy. Given the breadth of compounds developed and potential therapeutic indications, we assessed the comparative pharmacology of six investigational histamine H3 agents, including pitolisant, using native tissue and recombinant cells. Whilst all of the compounds tested displayed robust histamine H3 receptor inverse agonism and did not differentiate between the main H3 receptor splice variants, they displayed a wide range of affinities and kinetic properties, and included rapidly dissociating (pitolisant, S 38093-2, ABT-239) and slowly dissociating (GSK189254, JNJ-5207852, PF-3654746) agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359639", "endSection": "abstract" }, { "offsetInBeginSection": 1574, "offsetInEndSection": 1814, "text": "Furthermore, pitolisant, ABT-239 and PF-3654746 also displayed appreciable sigma-1 receptor affinity, suggesting that this property differentiates clinically evaluated histamine H3 receptor antagonists and may play a role in their efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The pharmacological profile of pitolisant, a histamine H3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29802412", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 758, "text": " Clinical trials have demonstrated efficacy for the following classes of drugs as narcolepsy treatments: alerting medications (amphetamine, methylphenidate, modafinil/armodafinil, solriamfetol [JZP-110]), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), sodium oxybate, and the H3-receptor inverse agonist/antagonist pitolisant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30503715", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1726, "text": "In March 2016, the European Commission granted a marketing authorisation for pitolisant (WakixR) (as the first representative of the H3 inverse agonists) for the treatment of narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27787717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 520, "text": "The involvement of histamine H3 receptors (H3Rs) in memory is well known, and the potential of H3R antagonists in therapeutic management of neuropsychiatric diseases, e.g., Alzheimer disease (AD) is well established. Therefore, the effects of histamine H3 receptor (H3R) antagonist E159 (2.5-10 mg/kg, i.p.) in adult male rats on dizocilpine (DIZ)-induced memory deficits were studied in passive avoidance paradigm (PAP) and in novel object recognition (NOR) using pitolisant (PIT) and donepezil (DOZ) as standard drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29075190", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 303, "text": "Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28449891", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 862, "text": "The small molecule drug, pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus increasing histaminergic tone in the wake promoting system of the brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28490912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Pitolisant: First Global Approval.Pitolisant (Wakix\u2122) is an inverse agonist of the histamine H3 receptor that is being developed by Bioproject. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27438291", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness.Pitolisant could constitute an acceptable alternative for the treatment of refractory sleepiness in teenagers with narcolepsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22356925", "endSection": "title" }, { "offsetInBeginSection": 398, "offsetInEndSection": 622, "text": "In contrast, Pitolisant is a non-imidazole H3 receptor inverse agonist that has already been tested in clinical trials but it remains to be determined whether this compound also potentiates the behavioral effects of cocaine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "BACKGROUND\nPitolisant (BF2.649) is a nonimidazole histamine 3 receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27223666", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 302, "text": "Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28449891", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 334, "text": "We assessed the safety and efficacy of pitolisant (previously called BF2.649), a selective histamine H3 receptor inverse agonist that activates these neurons, in patients with narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107292", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 395, "text": "Pitolisant (BF2.649, 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride) was the first H3R inverse agonist that has been tested in human trials and is well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23327739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Pitolisant (Wakix\u2122) is an inverse agonist of the histamine H3 receptor that is being developed by Bioproject.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27438291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "OBJECTIVE AND DESIGN\nPitolisant (BF2.649) is a selective inverse agonist for the histamine H(3) receptor and was developed for the treatment of excessive daytime sleepiness in Parkinson disease, narcolepsy, and schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820944", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22356925", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND AND PURPOSE\nPitolisant, a histamine H\u2083 receptor inverse agonist/antagonist is currently under Phase III clinical trials for treatment of excessive daytime sleepiness namely in narcoleptic patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "OBJECTIVE AND DESIGN Pitolisant (BF2.649) is a selective inverse agonist for the histamine H(3) receptor and was developed for the treatment of excessive daytime sleepiness in Parkinson disease, narcolepsy, and schizophrenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820944", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND AND PURPOSE Pitolisant, a histamine H\u2083 receptor inverse agonist/antagonist is currently under Phase III clinical trials for treatment of excessive daytime sleepiness namely in narcoleptic patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472741", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 257, "text": "We assessed the safety and efficacy of pitolisant, a histamine H3 receptor inverse agonist, for treatment of cataplexy in patients with narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28129985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Preclinical evaluation of the abuse potential of Pitolisant, a histamine H\u2083 receptor inverse agonist/antagonist compared with Modafinil.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23472741", "endSection": "title" }, { "offsetInBeginSection": 322, "offsetInEndSection": 562, "text": "MATERIALS AND TREATMENTS: Behavioral effects of pitolisant and the structural different H(3) receptor inverse agonists ciproxifan and ST-889 were tested in zymosan-induced inflammation and the spared nerve injury model for neuropathic pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820944", "endSection": "abstract" } ] }, { "body": "Which methods have been developed for extracting sequence variants from the literature?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28200120", "http://www.ncbi.nlm.nih.gov/pubmed/23564842" ], "ideal_answer": [ "TmVar and nala" ], "exact_answer": [ [ "tmVar" ], [ "nala" ] ], "type": "list", "id": "5c56bbb107647bbc4b000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "tmVar: a text mining approach for extracting sequence variants in biomedical literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "title" }, { "offsetInBeginSection": 702, "offsetInEndSection": 1409, "text": "Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society. By doing so, we cover several important types of mutations that were not considered in past studies. Using a novel CRF label model and feature set, our method achieves higher performance than a state-of-the-art method on both our corpus (91.4 versus 78.1% in F-measure) and their own gold standard (93.9 versus 89.4% in F-measure). These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "nala: text mining natural language mutation mentions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28200120", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 709, "text": " The extraction of sequence variants from the literature remains an important task. Existing methods primarily target standard (ST) mutation mentions (e.g. 'E6V'), leaving relevant mentions natural language (NL) largely untapped (e.g. 'glutamic acid was substituted by valine at residue 6').Results: We introduced three new corpora suggesting named-entity recognition (NER) to be more challenging than anticipated: 28-77% of all articles contained mentions only available in NL. Our new method nala captured NL and ST by combining conditional random fields with word embedding features learned unsupervised from the entire PubMed. In our hands, nala substantially outperformed the state-of-the-art.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28200120", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 964, "text": "RESULTS\nHere, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1410, "text": "These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 964, "text": "RESULTS Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 981, "text": "As such, new automatic approaches are greatly needed for extracting different kinds of mutations with high accuracy.
RESULTS: Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1602, "text": "These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.
AVAILABILITY: tmVar software and its corpus of 500 manually curated abstracts are available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/pub/tmVar
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1389, "text": "These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 943, "text": "Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23564842", "endSection": "abstract" } ] }, { "body": "Which molecules are targeted by defactinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26530902", "http://www.ncbi.nlm.nih.gov/pubmed/30444612", "http://www.ncbi.nlm.nih.gov/pubmed/29145097", "http://www.ncbi.nlm.nih.gov/pubmed/27025608", "http://www.ncbi.nlm.nih.gov/pubmed/26334219", "http://www.ncbi.nlm.nih.gov/pubmed/29314097", "http://www.ncbi.nlm.nih.gov/pubmed/28881794" ], "ideal_answer": [ "PURPOSE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2." ], "exact_answer": [ [ "focal adhesion kinase" ], [ "proline-rich tyrosine kinase-2" ] ], "type": "list", "id": "5c6f107c7c78d69471000051", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "LC-ESI-MS/MS determination of defactinib, a novel FAK inhibitor in mice plasma and its application to a pharmacokinetic study in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29145097", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Effect of FAK inhibitor VS-6063 (defactinib) on docetaxel efficacy in prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29314097", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 517, "text": "Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29314097", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 896, "text": "Here, we report the development of a selective and potent Fak degrader, PROTAC-3, which outperforms a clinical candidate, defactinib, with respect to Fak activation as well as Fak-mediated cell migration and invasion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30444612", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 698, "text": "Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28881794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "PURPOSE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27025608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "OBJECTIVE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26334219", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1295, "text": "Accordingly, treatment of C4-2B4 cells with integrin ligands resulted in increased pFAK-Y397 expression and cell survival, whereas targeting integrins with FAK inhibitors PF-562271 or defactinib inhibited FAK phosphorylation and reduced the survival of PC3-mm2 cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVE\nVS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26334219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "PURPOSE\nVS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27025608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVE VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26334219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "PURPOSE VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27025608", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1294, "text": "Accordingly, treatment of C4-2B4 cells with integrin ligands resulted in increased pFAK-Y397 expression and cell survival, whereas targeting integrins with FAK inhibitors PF-562271 or defactinib inhibited FAK phosphorylation and reduced the survival of PC3-mm2 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530902", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1290, "text": "Accordingly, treatment of C4-2B4 cells with integrin ligands resulted in increased pFAK-Y397 expression and cell survival, whereas targeting integrins with FAK inhibitors PF-562271 or defactinib inhibited FAK phosphorylation and reduced the survival of PC3-mm2 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530902", "endSection": "abstract" } ] }, { "body": "What is Chrysophanol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30129050", "http://www.ncbi.nlm.nih.gov/pubmed/29698620", "http://www.ncbi.nlm.nih.gov/pubmed/29344652", "http://www.ncbi.nlm.nih.gov/pubmed/29367091", "http://www.ncbi.nlm.nih.gov/pubmed/29497904", "http://www.ncbi.nlm.nih.gov/pubmed/27171670", "http://www.ncbi.nlm.nih.gov/pubmed/29609691" ], "ideal_answer": [ "Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells", "Chrysophanol is a unique anthraquinone having broad-spectrum therapeutic potential along with ecological importance. A plethora of literature is available on the pharmacological properties of chrysophanol, which include anticancer, anti-inflammatory, and antimicrobial activities." ], "type": "summary", "id": "5c6dbda27c78d69471000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344652", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 279, "text": "Chrysophanol, an anthraquinone derivative isolated from the rhizomes of rheumpalmatum, has been reported to have a protective effect against lipopolysaccharide(LPS)-induced inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29367091", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 362, "text": "Chrysophanol (CHR) is one of traditional Chinese medicine which was reported to show protective effects in cognition dysfunction and inflammatory in previously studies. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29497904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Chrysophanol is a phytochemical typically extracted from rhubarb. Similar to other extracts from rhubarb, chrysophanol possesses anticancer activity against diverse cancerous cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30129050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Chrysophanol induces cell death and inhibits invasiveness via mitochondrial calcium overload in ovarian cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30129050", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Chrysophanol inhibits proliferation and induces apoptosis through NF-\u03baB/cyclin D1 and NF-\u03baB/Bcl-2 signaling cascade in breast cancer cell lines.Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344652", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Chrysophanol ameliorates high-fat diet-induced obesity and inflammation in neonatal rats.Chrysophanol is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Chinese Medicine. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29609691", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Chrysophanol is an anthraquinone compound, mainly isolated from rhubarb, with anti-cancer effects on some types of cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27171670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Chrysophanol, a major anthraquinone component occurring in many traditional Chinese herbs, is accepted as important active component with various pharmacological actions such as antibacterial and anticancer activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29698620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344652", "endSection": "abstract" } ] }, { "body": "What is the percentage of individuals at risk of dominant medically actionable disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30291343" ], "ideal_answer": [ "1 in 38 individuals at risk of a dominant medically actionable disease.", "1 in 38 healthy individuals (2.7%) has a (likely) pathogenic variant in one of 59 medically actionable dominant disease genes for which the American College of Medical Genetics and Genomics (ACMG) recommends disclosure." ], "exact_answer": [ "2.7%", "1/38" ], "type": "factoid", "id": "5c51fe8907ef653866000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "1 in 38 individuals at risk of a dominant medically actionable disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30291343", "endSection": "title" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1050, "text": "Our study shows that 1 in 38 healthy individuals (2.7%) has a (likely) pathogenic variant in one of 59 medically actionable dominant disease genes for which the American College of Medical Genetics and Genomics (ACMG) recommends disclosure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30291343", "endSection": "abstract" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1121, "text": "Our study shows that 1 in 38 healthy individuals (2.7%) has a (likely) pathogenic variant in one of 59 medically actionable dominant disease genes for which the American College of Medical Genetics and Genomics (ACMG) recommends disclosure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30291343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "1 in 38 individuals at risk of a dominant medically actionable disease.Clinical genomic sequencing can identify pathogenic variants unrelated to the initial clinical question, but of medical relevance to the patients and their families. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30291343", "endSection": "title" } ] }, { "body": "Please list the 4 genes involved in Sanfilippo syndrome, also known as mucopolysaccharidosis III (MPS-III).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27100513", "http://www.ncbi.nlm.nih.gov/pubmed/21910976" ], "ideal_answer": [ "Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of the four enzymes involved in the catabolism of glycosaminoglycan heparan sulfate. The genes are SGSH, NAGLU, HGSNAT or GNS." ], "exact_answer": [ [ "SGSH" ], [ "NAGLU" ], [ "HGSNAT" ], [ "GNS" ] ], "type": "list", "id": "5c6ffa257c78d69471000056", "snippets": [ { "offsetInBeginSection": 213, "offsetInEndSection": 659, "text": "This disease is a complex of four conditions caused by dysfunctions of one of genes coding for lysosomal enzymes involved in degradation of heparan sulfate: SGSH (coding for heparan N-sulfatase) - causing MPS IIIA, NAGLU (coding for alpha-N-acetylglucosaminidase) - causing MPS IIIB, HGSNAT (coding for acetyl CoA alpha-glucosaminide acetyltransferase) - causing MPS IIIC), and GNS (coding for N-acetylglucosamine-6-sulfatase) - causing MPS IIID.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27100513", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 554, "text": "MPS III results from a deficiency in one of the four enzymes involved in the heparan sulfate degradation, with sulfamidase (SGSH), \u03b1-N-acetylglucosaminidase (NAGLU), acetyl-coenzyme A: \u03b1-glucosaminide N-acetyltransferase (HGSNAT), and N-acetylglucosamine-6-sulfatase (GNS) being deficient respectively in MPS IIIA, MPS IIIB, MPS IIIC and MPS IIID. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21910976", "endSection": "abstract" } ] }, { "body": "What is CardioClassifier?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29369293" ], "ideal_answer": [ "CardioClassifier (http://www.cardioclassifier.org) is a semiautomated decision support tool for clinical genome interpretation. CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data." ], "type": "summary", "id": "5c56c5e107647bbc4b000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "PURPOSE: Internationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed CardioClassifier ( http://www.cardioclassifier.org ), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 714, "text": "CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1705, "text": "CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data.CONCLUSION: CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation.CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "title" }, { "offsetInBeginSection": 338, "offsetInEndSection": 522, "text": "METHODS\nCardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1710, "text": "CONCLUSION\nCardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 335, "text": "Here we developed CardioClassifier ( http://www.cardioclassifier.org ), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 880, "text": "RESULTS\nWe benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1277, "text": "CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1710, "text": "CONCLUSION CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 522, "text": "METHODS CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 539, "text": "Here we developed CardioClassifier ( http://www.cardioclassifier.org ), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).
METHODS: CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 906, "text": "Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules.
RESULTS: We benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1328, "text": "A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher's P\u2009=\u20091.1\u2009 \u00d7 \u200910
CONCLUSION: CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1669, "text": "CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 504, "text": "CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 327, "text": "Here we developed CardioClassifier ( http://www.cardioclassifier.org ), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369293", "endSection": "abstract" } ] }, { "body": "List clinical disorders or diseases where uc.189 is involved?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "http://www.ncbi.nlm.nih.gov/pubmed/28941722" ], "ideal_answer": [ "Univariate and multivariate Cox regression analysis demonstrated that over-expression of uc.189 predicted poor prognosis in Cervical squamous cell carcinomas (CSCC) and Endometrial adenocarcinomas (EAC). Thus, several findings suggested uc.189 might be an evaluating prognosis marker of gynecological tumors. In addition, high expression of uc.189 might reflect poor prognosis of Esophageal squamous cell carcinoma (ESCC) and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target." ], "exact_answer": [ [ "Esophageal squamous cell carcinoma", "ESCC" ], [ "Cervical squamous cell carcinomas", "CSCCs", "gynecological tumors" ], [ "Endometrial adenocarcinomas", "EACs", "gynecological tumors" ] ], "type": "list", "id": "5c580fe107647bbc4b00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Expression of uc.189 and its clinicopathologic significance in gynecological cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 391, "text": "Until now, the role of uc.189 in human cancers remains undefined and the clinical significance of uc.189 in gynecological cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in gynecological cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 1212, "text": "Tissue microarrays were constructed with 243 samples including 116 cervical squamous cell carcinomas (CSCCs), 98 endometrial adenocarcinomas (EACs), 29 ovarian cystoadenocarcinomas(OCAs), and corresponding normal tissues. In CSCC, uc.189 expression was increased in 78.5% of cases (91/116), decreased in 4.3% (5/116), and unchanged in 17.2% (20/116). In EAC its expression was increased in 74.5% (73/98), decreased in 3.1% (3/98), and unchanged in 22.4% (22/98). Expression of uc.189 was increased in 23, and unchanged/decreased in 6, of 29 cases of ovarian cystoadenocarcinomas. Univariate and multivariate Cox regression analysis demonstrated that over-expression of uc.189 predicted poor prognosis in CSCC and EAC. Thus, these findings suggested uc.189 might be an evaluating prognosis marker of gynecological tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Upregulation of uc.189 in patients with esophageal squamous cell carcinoma and its clinicopathologic value.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1272, "text": "Ultraconserved elements (UCEs) encoding noncoding RNAs serve as important regulators in cancer biology. Until now, the role of the UCE uc.189 in human cancers remains undefined and the clinical significance of uc.189 in esophageal cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in esophageal squamous cell carcinomas (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC. The correlation of uc.189 with clinicopathological features and prognosis were also analyzed. The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis. High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1272, "text": "Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 999, "text": "The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 255, "text": "Until now, the role of the UCE uc.189 in human cancers remains undefined and the clinical significance of uc.189 in esophageal cancers remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1123, "text": "High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 371, "text": "This study was to identify the prognostic value of uc.189 expression in esophageal squamous cell carcinomas (ESCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 296, "text": "Until now, the role of uc.189 in human cancers remains undefined and the clinical significance of uc.189 in gynecological cancers remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1212, "text": "Thus, these findings suggested uc.189 might be an evaluating prognosis marker of gynecological tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1109, "text": "Univariate and multivariate Cox regression analysis demonstrated that over-expression of uc.189 predicted poor prognosis in CSCC and EAC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 391, "text": "This study was to identify the prognostic value of uc.189 expression in gynecological cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 742, "text": "In CSCC, uc.189 expression was increased in 78.5% of cases (91/116), decreased in 4.3% (5/116), and unchanged in 17.2% (20/116).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1275, "text": "Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 1002, "text": "The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 1003, "offsetInEndSection": 1126, "text": "High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941722", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 971, "text": "Expression of uc.189 was increased in 23, and unchanged/decreased in 6, of 29 cases of ovarian cystoadenocarcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29484123", "endSection": "abstract" } ] }, { "body": "Is verubecestat effective for Alzheimer\u2019s Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29461065", "http://www.ncbi.nlm.nih.gov/pubmed/28749667", "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "http://www.ncbi.nlm.nih.gov/pubmed/29397980" ], "ideal_answer": [ "No. Verubecestat is not effective for treatment of Alzheimer\u2019s Disease." ], "exact_answer": "no", "type": "yesno", "id": "5c6b82a17c78d6947100002f", "snippets": [ { "offsetInBeginSection": 350, "offsetInEndSection": 550, "text": " The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28749667", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 508, "text": "This reaction was applied to the preparation of verubecestat, which is currently undergoing clinical evaluation for the treatment of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29461065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Verubecestat is an inhibitor of \u03b2-site amyloid precursor protein cleaving enzyme 1 (BACE1) being evaluated in clinical trials for the treatment of Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29397980", "endSection": "abstract" }, { "offsetInBeginSection": 2341, "offsetInEndSection": 2526, "text": "CONCLUSIONS: Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease.Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "endSection": "title" }, { "offsetInBeginSection": 2347, "offsetInEndSection": 2530, "text": "CONCLUSIONS\nVerubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "endSection": "abstract" }, { "offsetInBeginSection": 2314, "offsetInEndSection": 2485, "text": "Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "endSection": "abstract" } ] }, { "body": "What is the role of metalloproteinase-17 (ADAM17) in NK cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23625205", "http://www.ncbi.nlm.nih.gov/pubmed/24941379", "http://www.ncbi.nlm.nih.gov/pubmed/17510296", "http://www.ncbi.nlm.nih.gov/pubmed/30009514", "http://www.ncbi.nlm.nih.gov/pubmed/25816339", "http://www.ncbi.nlm.nih.gov/pubmed/19395875", "http://www.ncbi.nlm.nih.gov/pubmed/21480393", "http://www.ncbi.nlm.nih.gov/pubmed/27077118", "http://www.ncbi.nlm.nih.gov/pubmed/20871631", "http://www.ncbi.nlm.nih.gov/pubmed/29978334" ], "ideal_answer": [ "The metalloproteinase-17 (ADAM17) is involved in CD16A cleavage and acts as a regulatory checkpoint in NK cells" ], "type": "summary", "id": "5c6ffc5b7c78d69471000057", "snippets": [ { "offsetInBeginSection": 953, "offsetInEndSection": 1142, "text": " To address this concern, bispecific or trispecific engagers that target NK cells to the tumour and an ADAM17 inhibitor that prevents CD16 shedding after NK cell activation are being tested", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30009514", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1566, "text": "ese findings support ADAM17 as a dynamic inhibitory checkpoint of the potent activating receptor CD16A, which can be targeted by MEDI3622 to potentially increase the efficacy of anti-tumor therapeutic antibodie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29978334", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1320, "text": "Our findings provide further characterization of CD16 cleavage by ADAM17 and they demonstrate that a non-cleavable version of CD16a can be expressed in engineered NK cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25816339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "CD16a and CD16b are IgG Fc receptors expressed by human natural killer (NK) cells and neutrophils, respectively. Both CD16 isoforms undergo a rapid down-regulation in expression by ADAM17-mediated proteolytic cleavage upon cell activation by various stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25816339", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 1013, "text": "Bispecific or trispecific killer engagers that target CD16 on NK cells to enhance recognition of tumor antigens, and desintegrin and metalloproteinase 17 (ADAM17) inhibition that prevents CD16 shedding after NK-cell activation should promote enhanced killing of cancer with specificity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24941379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Role of ADAM17 in the ectodomain shedding of TNF-alpha and its receptors by neutrophils and macrophages.TNF-alpha and its receptors TNFRI and TNFRII are cleaved from the surface of leukocytes by a proteolytic process referred to as ectodomain shedding. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17510296", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "A disintegrin and metalloproteinase-17 (ADAM17) is involved in proteolytic ectodomain shedding of several membrane-bound growth factors and cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21480393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "A disintegrin and metalloproteinase-17 (ADAM17) is involved in proteolytic ectodomain shedding of several membrane-bound growth factors and cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19395875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "A disintegrin and metalloproteinase-17 (ADAM17) is a member of the metalloproteinase superfamily and involved in the cleavage of ectodomain of many transmembrane proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23625205", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 1014, "text": "Bispecific or trispecific killer engagers that target CD16 on NK cells to enhance recognition of tumor antigens, and desintegrin and metalloproteinase 17 (ADAM17) inhibition that prevents CD16 shedding after NK-cell activation should promote enhanced killing of cancer with specificity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24941379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "ADAM17 (a disintegrin and metalloproteinase 17, also referred to as TNF\u03b1 converting enzyme or TACE) is a cell-surface metalloproteinase that regulates signaling via the epidermal growth factor receptor (EGFR) and has important roles in diseases such as cancer and rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20871631", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 360, "text": "Here we demonstrate that a disintegrin and metalloproteinase-17 (ADAM17), a main sheddase for tumor necrosis factor (TNF)-\u03b1, is essential for defensive epithelial properties against UC by promoting epithelial cell growth and goblet cell differentiation in mouse and human.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27077118", "endSection": "abstract" } ] }, { "body": "What is the triad of Melkersson-Rosenthal syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15281985", "http://www.ncbi.nlm.nih.gov/pubmed/29065902", "http://www.ncbi.nlm.nih.gov/pubmed/15865255", "http://www.ncbi.nlm.nih.gov/pubmed/10938204", "http://www.ncbi.nlm.nih.gov/pubmed/15942506", "http://www.ncbi.nlm.nih.gov/pubmed/12150220", "http://www.ncbi.nlm.nih.gov/pubmed/10332378", "http://www.ncbi.nlm.nih.gov/pubmed/12783021", "http://www.ncbi.nlm.nih.gov/pubmed/24827666", "http://www.ncbi.nlm.nih.gov/pubmed/27081272", "http://www.ncbi.nlm.nih.gov/pubmed/27165478", "http://www.ncbi.nlm.nih.gov/pubmed/28955585", "http://www.ncbi.nlm.nih.gov/pubmed/8725591", "http://www.ncbi.nlm.nih.gov/pubmed/2160251", "http://www.ncbi.nlm.nih.gov/pubmed/22836908", "http://www.ncbi.nlm.nih.gov/pubmed/29766816", "http://www.ncbi.nlm.nih.gov/pubmed/29554155", "http://www.ncbi.nlm.nih.gov/pubmed/1561252", "http://www.ncbi.nlm.nih.gov/pubmed/30217753", "http://www.ncbi.nlm.nih.gov/pubmed/17103360", "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "http://www.ncbi.nlm.nih.gov/pubmed/6743105" ], "ideal_answer": [ "Melkersson-Rosenthal syndrome is an uncommon granulomatous disease characterized by the triad of relapsing facial paralysis, orofacial edema and fissured tongue." ], "exact_answer": [ [ "relapsing facial paralysis" ], [ "orofacial edema" ], [ "fissured tongue" ] ], "type": "list", "id": "5c6f14297c78d69471000052", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare syndrome of facial nerve palsy, facial edema, and lingua plicata that can be difficult to treat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "BACKGROUND AND OBJECTIVE: Melkersson Rosenthal syndrome (MRS) is a rare disorder of unknown etiology and comprises the triad: orofacial edema, recurrent facial paralysis and lingua plicata. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29766816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Melkersson Rosenthal syndromes (MRS) is a rare autosomal dominantly inherited neurocutaneous syndrome characterised by a triad of facial (seventh cranial) nerve palsy, recurrent orofacial swelling and fissuring of the tongue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30217753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Melkersson-Rosenthal Syndrome (MRS) is a rare disorder consisting of a triad of persistent or recurrent orofacial edema, relapsing facial paralysis and fissured tongue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28955585", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 422, "text": "When it presents in a triad encompassing facial nerve palsy, lip swelling, and fissured or furrowed tongue it is called Melkersson-Rosenthal syndrome while monosymptomatic or oligosymptomatic forms are referred to as granulomatous cheilitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29065902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Melkersson-Rosenthal syndrome (MRS) is an uncommon granulomatous disease characterized by the triad of relapsing facial paralysis, orofacial swelling, and fissured tongue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27081272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Melkersson Rosenthal Syndrome is a rare neuro-mucocutaneous disorder characterized by the classic triad of facial swelling, recurrent facial nerve palsy and fissured tongue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27165478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Melkersson-Rosenthal syndrome: review of the literature and case report of a 10-year misdiagnosis.Melkersson-Rosenthal syndrome is classically described as a triad of orofacial swelling, facial palsy, and fissured tongue. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10332378", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "The Melkersson-Rosenthal syndrome: a retrospective study of biopsied cases.Melkersson-Rosenthal syndrome (MRS) is a rare neuromucocutaneous syndrome marked by the triad of recurrent nonpitting orofacial edema, fissured dorsal tongue (lingua plicata), and lower motoneuron facial paralysis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22836908", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Melkersson-Rosenthal syndrome in the periocular area: a review of the literature and case report.A triad of facial palsy, facial edema, and furrowed tongue characterizes Melkersson-Rosenthal syndrome, a rare, noncaseating granulomatous disease of unknown cause. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783021", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Melkersson-Rosenthal syndrome: report of three cases.Melkersson-Rosenthal syndrome is a rare disorder consisting of the triad of persistent or recurrent orofacial edema, relapsing facial paralysis and fissured tongue. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10938204", "endSection": "title" }, { "offsetInBeginSection": 115, "offsetInEndSection": 254, "text": "Melkersson-Rosenthal syndrome is characterised by a triad of recurrent orofacial swelling, relapsing facial paralysis, and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17103360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare neuromucocutaneous syndrome marked by the triad of recurrent nonpitting orofacial edema, fissured dorsal tongue (lingua plicata), and lower motoneuron facial paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22836908", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1150, "text": "The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 451, "text": "RECENT FINDINGS\nThe Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The Melkersson-Rosenthal syndrome is a rare disorder of unknown etiology characterized by a triad of recurrent orofacial swelling, relapsing facial paralysis, and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8725591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Melkersson-Rosenthal syndrome is classically described as a triad of orofacial swelling, facial palsy, and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10332378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A triad of facial palsy, orofacial edema, and furrowed tongue constitutes an uncommon condition known as Melkersson-Rosenthal syndrome (MRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1561252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Melkersson-Rosenthal syndrome is an uncommon disorder characterized by a triad of facial nerve palsy, orofacial edema, and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15942506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Melkersson-Rosenthal syndrome is a rare disorder consisting of the triad of persistent or recurrent orofacial edema, relapsing facial paralysis and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10938204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of recurrent facial palsy, lingua plicata, and facial edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12150220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Melkersson-Rosenthal syndrome (MRS) is a rare granulomatous inflammatory disease characterised by the triad of orofacial oedema, facial nerve palsy and furrowed tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24827666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Melkersson Rosenthal Syndrome is a rare neuro-mucocutaneous disorder characterized by the classic triad of facial swelling, recurrent facial nerve palsy and fissured tongue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27165478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The Melkersson-Rosenthal syndrome (MRS) is a rare condition characterized by the triad of familial relapsing peripheral facial palsy, facial edema, and lingua plicata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6743105", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 451, "text": "RECENT FINDINGS The Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26698837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Melkersson-Rosenthal syndrome is an uncommon disorder of uncertain aetiology characterized by orofacial oedema, facial nerve palsy and lingua plicata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15281985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Melkersson-Rosenthal syndrome is a rare condition, classically associated with a triad of facial and/or lip edema, fissured tongue, and relapsing facial palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2160251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The Melkersson-Rosenthal syndrome consists of triad of symptoms: recurrent oedema of lips, recurrent facial nerve paralysis and lingua plicata.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15865255", "endSection": "abstract" } ] }, { "body": "Is galcanezumab effective for treatment of migraine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29616494", "http://www.ncbi.nlm.nih.gov/pubmed/30341990", "http://www.ncbi.nlm.nih.gov/pubmed/29310444", "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "http://www.ncbi.nlm.nih.gov/pubmed/30182284", "http://www.ncbi.nlm.nih.gov/pubmed/29089894", "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "http://www.ncbi.nlm.nih.gov/pubmed/30413151", "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "http://www.ncbi.nlm.nih.gov/pubmed/29848108", "http://www.ncbi.nlm.nih.gov/pubmed/30446596", "http://www.ncbi.nlm.nih.gov/pubmed/30378008" ], "ideal_answer": [ "Yes. Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide that is used for migraine prevention." ], "exact_answer": "yes", "type": "yesno", "id": "5c6f15577c78d69471000053", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Importance: Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 2102, "offsetInEndSection": 2353, "text": "Conclusions and Relevance: Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Background Safety findings from a Phase 2b study of galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, for prevention of migraine (NCT02163993) are reported here.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310444", "endSection": "title" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1633, "text": "Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long-term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 778, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 360, "text": "Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29616494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29848108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29848108", "endSection": "title" }, { "offsetInBeginSection": 516, "offsetInEndSection": 723, "text": "Galcanezumab induced a robust, dose-dependent, and durable inhibition of capsaicin-induced increase in DBF, supporting the continued clinical development of galcanezumab for prophylaxis in migraine patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29089894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis.Based on the results of this meta-analysis, CGRP monoclonal antibodies significantly reduced the monthly migraine days and acute migraine-specific medication. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30182284", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Importance\nGalcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 1709, "offsetInEndSection": 1817, "text": "Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446596", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 366, "text": "BACKGROUND\nGalcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30341990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "BACKGROUND\nGalcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (\u22646-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413151", "endSection": "abstract" }, { "offsetInBeginSection": 2033, "offsetInEndSection": 2210, "text": "CONCLUSION\nTwelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413151", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 777, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 2114, "offsetInEndSection": 2363, "text": "Conclusions and Relevance\nMonthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Importance Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "BACKGROUND Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (\u22646-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413151", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 366, "text": "BACKGROUND Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30341990", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1333, "text": "Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo -2.7, galcanezumab 120 mg -4.8, galcanezumab 240 mg -4.6) (
CONCLUSIONS: Both doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446596", "endSection": "abstract" }, { "offsetInBeginSection": 1334, "offsetInEndSection": 1678, "text": "Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.
CLINICALTRIALSGOV IDENTIFIER: NCT02614261.
CLASSIFICATION OF EVIDENCE: This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446596", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 412, "text": "In September 2018, the US FDA approved galcanezumab as a once-monthly subcutaneous injection for the preventive treatment of migraine in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30378008", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 860, "text": "This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30378008", "endSection": "abstract" }, { "offsetInBeginSection": 1678, "offsetInEndSection": 1786, "text": "Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446596", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 856, "text": "This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30378008", "endSection": "abstract" }, { "offsetInBeginSection": 2003, "offsetInEndSection": 2169, "text": "Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413151", "endSection": "abstract" } ] }, { "body": "Can mitochondria be inherited by both parents in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30478036" ], "ideal_answer": [ "Yes. A comprehensive exploration of mtDNA segregation in certain families shows biparental mtDNA transmission with an autosomal dominant-like inheritance mode. Although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring." ], "exact_answer": "yes", "type": "yesno", "id": "5c52028807ef653866000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Biparental Inheritance of Mitochondrial DNA in Humans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30478036", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1017, "text": "Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30478036", "endSection": "abstract" } ] }, { "body": "Can Diazepam be beneficial in the treatment of traumatic brain injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10760494", "http://www.ncbi.nlm.nih.gov/pubmed/8877308" ], "ideal_answer": [ "Diazepam treatment improved cognitive recovery and mortality in brain injured rats." ], "exact_answer": "yes", "type": "yesno", "id": "5c71648b7c78d69471000067", "snippets": [ { "offsetInBeginSection": 281, "offsetInEndSection": 462, "text": "he present experiment examined the effects of diazepam, a positive modulator at the GABA(A) receptor, on survival and cognitive performance in traumatically brain-injured animals. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10760494", "endSection": "abstract" } ] }, { "body": "Name the algorithms for counting multi-mapping reads", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29444201", "http://www.ncbi.nlm.nih.gov/pubmed/28915787" ], "ideal_answer": [ "RNA-Seq is currently used routinely, and it provides accurate information on gene transcription. However, the method cannot accurately estimate duplicated genes expression. Several strategies have been previously used (drop duplicated genes, distribute uniformly the reads, or estimate expression), but all of them provide biased results. Mmquant is a tool for computing gene expression, including duplicated genes. If a read maps at different positions, the tool detects that the corresponding genes are duplicated; it merges the genes and creates a merged gene. The counts of ambiguous reads is then based on the input genes and the merged genes. Other methods have been developed that use weighted allocation of read counts but these methods treat the different types of multi-reads equivalently. For instance a hierarchical approach was developed for allocation of read counts that first resolves ambiguities among genes, then among isoforms, and lastly between alleles. The model has been implemented in EMASE software (Expectation-Maximization for Allele Specific Expression) to estimate total gene expression, isoform usage and ASE based on this hierarchical allocation." ], "exact_answer": [ [ "mmquant" ], [ "EMASE", "Expectation-Maximization for Allele Specific Expression" ] ], "type": "list", "id": "5c58282e07647bbc4b00001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "mmquant: how to count multi-mapping reads?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28915787", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 842, "text": "RNA-Seq is currently used routinely, and it provides accurate information on gene transcription. However, the method cannot accurately estimate duplicated genes expression. Several strategies have been previously used (drop duplicated genes, distribute uniformly the reads, or estimate expression), but all of them provide biased results.RESULTS: We provide here a tool, called mmquant, for computing gene expression, included duplicated genes. If a read maps at different positions, the tool detects that the corresponding genes are duplicated; it merges the genes and creates a merged gene. The counts of ambiguous reads is then based on the input genes and the merged genes.CONCLUSION: mmquant is a drop-in replacement of the widely used tools htseq-count and featureCounts that handles multi-mapping reads in an unabiased way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28915787", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1081, "text": "Allele-specific expression (ASE) refers to the differential abundance of the allelic copies of a transcript. RNA sequencing (RNA-seq) can provide quantitative estimates of ASE for genes with transcribed polymorphisms. When short-read sequences are aligned to a diploid transcriptome, read-mapping ambiguities confound our ability to directly count reads. Multi-mapping reads aligning equally well to multiple genomic locations, isoforms or alleles can comprise the majority (>85%) of reads. Discarding them can result in biases and substantial loss of information. Methods have been developed that use weighted allocation of read counts but these methods treat the different types of multi-reads equivalently. We propose a hierarchical approach to allocation of read counts that first resolves ambiguities among genes, then among isoforms, and lastly between alleles. We have implemented our model in EMASE software (Expectation-Maximization for Allele Specific Expression) to estimate total gene expression, isoform usage and ASE based on this hierarchical allocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29444201", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "mmquant: how to count multi-mapping reads?mmquant is a drop-in replacement of the widely used tools htseq-count and featureCounts that handles multi-mapping reads in an unabiased way.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28915787", "endSection": "title" }, { "offsetInBeginSection": 693, "offsetInEndSection": 845, "text": "CONCLUSION\nmmquant is a drop-in replacement of the widely used tools htseq-count and featureCounts that handles multi-mapping reads in an unabiased way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28915787", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 845, "text": "CONCLUSION mmquant is a drop-in replacement of the widely used tools htseq-count and featureCounts that handles multi-mapping reads in an unabiased way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28915787", "endSection": "abstract" } ] }, { "body": "In clinical trials, the H3 R antagonist CEP-26401 has a positive effect on cognition, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27222271", "http://www.ncbi.nlm.nih.gov/pubmed/18469850", "http://www.ncbi.nlm.nih.gov/pubmed/22001260" ], "ideal_answer": [ "The H3 R antagonist CEP-26401 had an effect on cognition.", "CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement" ], "exact_answer": "yes", "type": "yesno", "id": "5c57216e07647bbc4b000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27222271", "endSection": "abstract" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1565, "text": "hese results demonstrate potent behavioral effects of CEP-26401 in rodent models and suggest that this novel H\u2083R antagonist may have therapeutic utility in the treatment of cognitive and attentional disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22001260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27222271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "CEP-26401 (irdabisant), a potent and selective histamine H\u2083 receptor antagonist/inverse agonist with cognition-enhancing and wake-promoting activities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22001260", "endSection": "title" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1451, "text": "However, although a number of clinical studies examining the efficacy of H3 receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H3 receptor antagonist has been reported to date.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18469850", "endSection": "abstract" }, { "offsetInBeginSection": 1511, "offsetInEndSection": 1627, "text": "Further clinical studies are required to establish the potential of low-dose CEP-26401 in cognition enhancement.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27222271", "endSection": "abstract" } ] }, { "body": "Fecal transplantation is used to treat infection with what bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28178876", "http://www.ncbi.nlm.nih.gov/pubmed/27999162", "http://www.ncbi.nlm.nih.gov/pubmed/27194400", "http://www.ncbi.nlm.nih.gov/pubmed/29104169", "http://www.ncbi.nlm.nih.gov/pubmed/29450831", "http://www.ncbi.nlm.nih.gov/pubmed/29020255", "http://www.ncbi.nlm.nih.gov/pubmed/27648772", "http://www.ncbi.nlm.nih.gov/pubmed/28506071", "http://www.ncbi.nlm.nih.gov/pubmed/25548572", "http://www.ncbi.nlm.nih.gov/pubmed/26204547", "http://www.ncbi.nlm.nih.gov/pubmed/28195180", "http://www.ncbi.nlm.nih.gov/pubmed/29076071", "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "http://www.ncbi.nlm.nih.gov/pubmed/24939885", "http://www.ncbi.nlm.nih.gov/pubmed/26616138", "http://www.ncbi.nlm.nih.gov/pubmed/23844515", "http://www.ncbi.nlm.nih.gov/pubmed/26901316", "http://www.ncbi.nlm.nih.gov/pubmed/24440934", "http://www.ncbi.nlm.nih.gov/pubmed/28125667" ], "ideal_answer": [ "Fecal microbiota transplantation is used to treat Clostridium difficile infection" ], "exact_answer": [ "Clostridium difficile" ], "type": "factoid", "id": "5c71d6d27c78d6947100006a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Fecal microbiota transplantation is a highly effective intervention for patients suffering from recurrent Clostridium difficile, a common hospital-acquired infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28178876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Mini-Fecal Microbiota Transplantation for Treatment of Clostridium difficile Proctitis Following Total Colectomy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29020255", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 127, "text": "We aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria.Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "endSection": "title" }, { "offsetInBeginSection": 605, "offsetInEndSection": 879, "text": "Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review.Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29450831", "endSection": "title" }, { "offsetInBeginSection": 288, "offsetInEndSection": 367, "text": "Recently, fecal microbiota transplantation (FMT) has been applied to treat CDI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29076071", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 495, "text": "While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection following Fecal Microbiota Transplantation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27999162", "endSection": "title" }, { "offsetInBeginSection": 1756, "offsetInEndSection": 1974, "text": "Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1822, "text": "Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 350, "text": "While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 772, "text": "Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616138", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1121, "text": "Here we present the case of a child with SBS and recurrent, debilitating D-lactic acidosis, which was successfully treated with fecal transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616138", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 321, "text": "Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24939885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Fecal microbiota transplantation (FMT) has an incomparable efficacy to treat recurrent Clostridium difficile infection, with near 90% of success.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26204547", "endSection": "abstract" }, { "offsetInBeginSection": 1937, "offsetInEndSection": 2131, "text": "Fecal microbiota transplantation (FMT) has provided a successful treatment method for some patients with recurrent C. difficile infection, but its mechanism and long-term effects remain unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24939885", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 468, "text": "Fecal microbiota transplantation (FMT), a highly effective treatment for recurrent Clostridium difficile infection, has emerged as a promising therapy for intestinal MDR bacterial decolonization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27194400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "OBJECTIVES\nFecal microbiota transplantation (FMT) is increasingly being used for treatment of recurrent Clostridium difficile infection (R-CDI) that cannot be cured with antibiotics alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28195180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "BACKGROUND\nFecal microbiota transplantation (FMT) restores a diverse bacterial profile to the gastrointestinal tract and may effectively treat patients with Clostridium difficile infection (CDI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27648772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27999162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Fecal microbiota transplantation is a compelling treatment for recurrent Clostridium difficile infections, with potential applications against other diseases associated with changes in gut microbiota.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28125667", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 839, "text": "Fecal microbiota transplantation (FMT) holds considerable promise as a therapy for recurrent Clostridium difficile infection, but well-designed, randomized-controlled trials and Long-term follow-up registries are stilt required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23844515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) and is considered as a treatment for other gastrointestinal (GI) diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25548572", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 303, "text": "BACKGROUND Fecal microbiota microbiota transplantation from a healthy donor into an individual with CD infection (CDI) can resolve symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24440934", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 816, "text": "Fecal microbiota transplantation is relatively simple to perform, well-tolerated, safe and effective in recurrent Clostridium difficile infection with ulcerative pancolitis, as an alternative in case of antibiotic therapy failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28506071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The use of fecal microbiota transplantation in recurrent Clostridium difficile infection and coexistent inflammatory bowel disease remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28506071", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 329, "text": "Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24939885", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 310, "text": "Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24939885", "endSection": "abstract" }, { "offsetInBeginSection": 1607, "offsetInEndSection": 1825, "text": "Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23333862", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1678, "text": "Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26901316", "endSection": "abstract" } ] }, { "body": "Is pimavanserin effective for Parkinson's disease psychosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "http://www.ncbi.nlm.nih.gov/pubmed/24183563", "http://www.ncbi.nlm.nih.gov/pubmed/27609312", "http://www.ncbi.nlm.nih.gov/pubmed/29497575", "http://www.ncbi.nlm.nih.gov/pubmed/29185542", "http://www.ncbi.nlm.nih.gov/pubmed/29047301", "http://www.ncbi.nlm.nih.gov/pubmed/26908168", "http://www.ncbi.nlm.nih.gov/pubmed/28385039", "http://www.ncbi.nlm.nih.gov/pubmed/28622212", "http://www.ncbi.nlm.nih.gov/pubmed/28375643", "http://www.ncbi.nlm.nih.gov/pubmed/29452684", "http://www.ncbi.nlm.nih.gov/pubmed/28880354", "http://www.ncbi.nlm.nih.gov/pubmed/29098976", "http://www.ncbi.nlm.nih.gov/pubmed/29185820", "http://www.ncbi.nlm.nih.gov/pubmed/29105858", "http://www.ncbi.nlm.nih.gov/pubmed/27262680", "http://www.ncbi.nlm.nih.gov/pubmed/30298184", "http://www.ncbi.nlm.nih.gov/pubmed/26744739", "http://www.ncbi.nlm.nih.gov/pubmed/19907417", "http://www.ncbi.nlm.nih.gov/pubmed/28817967", "http://www.ncbi.nlm.nih.gov/pubmed/27830568", "http://www.ncbi.nlm.nih.gov/pubmed/29955528" ], "ideal_answer": [ "Yes. Pimavanserin is effective for treating Parkinson's disease psychosis. It is a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist." ], "exact_answer": "yes", "type": "yesno", "id": "5c6f6d997c78d69471000055", "snippets": [ { "offsetInBeginSection": 587, "offsetInEndSection": 791, "text": "Two cases of Parkinson's disease with an unusual delusional misidentification, intermetamorphosis, are presented, along with their improvement with pimavanserin, a novel atypical antipsychotic medication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29185820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "RATIONALE: Pimavanserin, a selective serotonin 2A receptor inverse agonist, is a promising candidate for treating Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29105858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "OBJECTIVE: Our aim was to describe the efficacy and tolerability of pimavanserin, a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP), using the metrics of number needed to treat (NNT) and number needed to harm (NNH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29098976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047301", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "INTRODUCTION: Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047301", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1256, "text": "A pivotal phase III clinical trial demonstrated significant improvement in PDP symptoms in patients receiving pimavanserin compared to placebo-treated patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047301", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1560, "text": "Pimavanserin's mechanism of action might contribute to its unique psychopharmacological properties in the improved treatment of PDP, and perhaps psychosis in other diseases including schizophrenia and dementia-related psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Pimavanserin (Nuplazid\u2122) for the treatment of Parkinson disease psychosis: A review of the literature.Options for the treatment of Parkinson disease psychosis are limited. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29955528", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Pimavanserin for the treatment of Parkinson's disease psychosis.Pimavanserin is an antipsychotic with a unique mechanism of action (5-HT2A receptor inverse agonist) and no measurable dopaminergic activity; it has been demonstrated to be efficacious, well tolerated and safe for the treatment of PDP. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27609312", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "A Retrospective Study of Pimavanserin Use in a Movement Disorders Clinic.Pimavanserin, a 5-HT2A inverse agonist, was commercially released in the United States in April 2016 for the treatment of Parkinson disease psychosis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622212", "endSection": "title" }, { "offsetInBeginSection": 85, "offsetInEndSection": 277, "text": "receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27830568", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Evidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis.Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28385039", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Pimavanserin: A novel therapeutic option for Parkinson disease psychosis.While pimavanserin appears to be a safe, effective, and well-tolerated therapeutic option for PDP, additional clinical trials and open-label extension studies are needed to determine the long-term safety and efficacy of this promising therapy. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29185542", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29497575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29497575", "endSection": "title" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1509, "text": "CONCLUSIONS\nPimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "OBJECTIVE\nTo summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1017, "text": "RESULTS\nPimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "BACKGROUND\nPimavanserin is a selective 5-HT2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047301", "endSection": "abstract" }, { "offsetInBeginSection": 1944, "offsetInEndSection": 2071, "text": "INTERPRETATION\nPimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Pimavanserin (ACP-103) is a selective inverse agonist of the 5-hydroxytryptamine 2A (5-HT2A) receptor intended to treat patients with Parkinson's disease psychosis (PDP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26744739", "endSection": "abstract" }, { "offsetInBeginSection": 2808, "offsetInEndSection": 3013, "text": "INTERPRETATION\nPimavanserin showed efficacy in patients with Alzheimer's disease psychosis at the primary endpoint (week 6) with an acceptable tolerability profile and without negative effect on cognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "[Pimavanserin: a new treatment for the Parkinson's disease psychosis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28880354", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19907417", "endSection": "title" }, { "offsetInBeginSection": 264, "offsetInEndSection": 444, "text": "Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30298184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Pimavanserin: A Novel Antipsychotic for Parkinson's Disease Psychosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28375643", "endSection": "title" }, { "offsetInBeginSection": 1357, "offsetInEndSection": 1509, "text": "CONCLUSIONS Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "OBJECTIVE To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1017, "text": "RESULTS Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 1050, "text": "If this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26908168", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1344, "text": "The development of pimavanserin as an antipsychotic opened a new therapeutic avenue in the treatment of PDP as well as targeting psychosis in other disorders such as Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28817967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "OBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28375643", "endSection": "abstract" }, { "offsetInBeginSection": 1944, "offsetInEndSection": 2071, "text": "INTERPRETATION Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24183563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "OBJECTIVE: To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 1043, "text": "Data were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population.
RESULTS: Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1544, "text": "Pimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding.
CONCLUSIONS: Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Pimavanserin (Nuplazid\u2122) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27262680", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 674, "text": "This article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27262680", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1084, "text": "In a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30298184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1460, "text": "Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 982, "text": "Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" } ] }, { "body": "When did delafloxacin receive its first approval in the USA for acute bacterial skin and skin structure infections?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28748399" ], "ideal_answer": [ "Delafoxacin received approval in the USA for the treatment of acute bacterial skin and skin structure infections in 2017." ], "exact_answer": [ "2017" ], "type": "factoid", "id": "5c0117fd133db5eb7800002a", "snippets": [ { "offsetInBeginSection": 169, "offsetInEndSection": 381, "text": "The drug is being investigated or considered as a treatment for various bacterial infections and in June 2017 received approval in the USA for the treatment of acute bacterial skin and skin structure infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748399", "endSection": "abstract" } ] }, { "body": "Erenumab, used to treat migraine headaches, binds to what protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30409109", "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "http://www.ncbi.nlm.nih.gov/pubmed/30242830", "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "http://www.ncbi.nlm.nih.gov/pubmed/30074549", "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "http://www.ncbi.nlm.nih.gov/pubmed/28835404", "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "http://www.ncbi.nlm.nih.gov/pubmed/30086681" ], "ideal_answer": [ "Erenumab binds to the CGRP receptor to treat migraine headaches" ], "exact_answer": [ "CGRP receptor" ], "type": "factoid", "id": "5c71d7ca7c78d6947100006b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 288, "text": "Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "endSection": "abstract" }, { "offsetInBeginSection": 1214, "offsetInEndSection": 1633, "text": "monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long-term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND\nMigraine prevention with erenumab and\u00a0migraine induction by calcitonin gene-related peptide (CGRP) both carry notable individual variance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30409109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Background We evaluated the effect of erenumab, a fully human monoclonal antibody that inhibits the canonical calcitonin gene-related peptide receptor, on migraine-related disability, impact, and health-related quality of life among patients with episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30086681", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 211, "text": "Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1305, "text": "Results - The US Food and Drug Administration (FDA) approved erenumab, an anti-CGRP receptor monoclonal antibody, for prevention of migraine May 17, 2018.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30242830", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 237, "text": "Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND\nWe tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1286, "text": "In addition, erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, received approval from the US Food and Drug Administration (FDA) for the prevention of migraine in May 2018.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30074549", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 777, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Amgen and Novartis are developing erenumab (AIMOVIG\u2122, erenumab-aooe)-a fully human monoclonal antibody calcitonin gene-related peptide (CGRP) receptor antagonist-for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "OBJECTIVE To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28835404", "endSection": "abstract" } ] }, { "body": "What are the CADD scores?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "http://www.ncbi.nlm.nih.gov/pubmed/29340599", "http://www.ncbi.nlm.nih.gov/pubmed/25871441", "http://www.ncbi.nlm.nih.gov/pubmed/27148939" ], "ideal_answer": [ "Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders. CADD is an integrative annotation built from more than 60 genomic features, and can score human single nucleotide variants and short insertion and deletions anywhere in the reference assembly." ], "type": "summary", "id": "5c58db1386df2b9174000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "CADD: predicting the deleteriousness of variants throughout the human genome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 902, "text": "Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders. CADD is an integrative annotation built from more than 60 genomic features, and can score human single nucleotide variants and short insertion and deletions anywhere in the reference assembly. CADD uses a machine learning model trained on a binary distinction between simulated de novo variants and variants that have arisen and become fixed in human populations since the split between humans and chimpanzees; the former are free of selective pressure and may thus include both neutral and deleterious alleles, while the latter are overwhelmingly neutral (or, at most, weakly deleterious) by virtue of having survived millions of years of purifying selection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 979, "text": "CADD uses a machine learning model trained on a binary distinction between simulated de novo variants and variants that have arisen and become fixed in human populations since the split between humans and chimpanzees; the former are free of selective pressure and may thus include both neutral and deleterious alleles, while the latter are overwhelmingly neutral (or, at most, weakly deleterious) by virtue of having survived millions of years of purifying selection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "CADD: predicting the deleteriousness of variants throughout the human genome.Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "endSection": "title" }, { "offsetInBeginSection": 157, "offsetInEndSection": 356, "text": "The recently developed combined annotation-dependent depletion (CADD) method generates predictive scores for single-nucleotide variants (SNVs) in all areas of the genome, including noncoding regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27148939", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 434, "text": "CADD is an integrative annotation built from more than 60 genomic features, and can score human single nucleotide variants and short insertion and deletions anywhere in the reference assembly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 902, "text": "CADD uses a machine learning model trained on a binary distinction between simulated de novo variants and variants that have arisen and become fixed in human populations since the split between humans and chimpanzees; the former are free of selective pressure and may thus include both neutral and deleterious alleles, while the latter are overwhelmingly neutral (or, at most, weakly deleterious) by virtue of having survived millions of years of purifying selection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371827", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 742, "text": "Using the ClinVar benchmark, CADD was the best tool for detecting the pathogenic variants that are mainly located in protein coding gene regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29340599", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 605, "text": "Overall, we found CADD scores do predict pathogenicity (Spearman's \u03c1 = 0.595, P < 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25871441", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 608, "text": "Overall, we found CADD scores do predict pathogenicity (Spearman's \u03c1 = 0.595, P < 0.001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25871441", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 348, "text": "The recently developed combined annotation-dependent depletion (CADD) method generates predictive scores for single-nucleotide variants (SNVs) in all areas of the genome, including noncoding regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27148939", "endSection": "abstract" } ] }, { "body": "What is a prolactinoma and where in the body would they be found?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29177641", "http://www.ncbi.nlm.nih.gov/pubmed/29074127", "http://www.ncbi.nlm.nih.gov/pubmed/28954263", "http://www.ncbi.nlm.nih.gov/pubmed/10686432" ], "ideal_answer": [ "Prolactinomas are the most common functional tumors of the pituitary gland." ], "type": "summary", "id": "5c53143b7e3cb0e231000013", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 126, "text": "Prolactinomas are pituitary tumors with a very low prevalence in childhood and adolescence compared to adulthood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28954263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Prolactinomas are the most frequent functioning pituitary adenomas,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29074127", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Prolactinomas are the most common secretory pituitary adenoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Prolactinoma is the most common type of primary pituitary tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10686432", "endSection": "abstract" } ] }, { "body": "Which integrin genes are activated by the immune system in inflammatory bowel disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28067908" ], "ideal_answer": [ "ITGA4, ITGB8, ITGAL and ICAM1. In all four cases, the expression-increasing allele also increases disease risk." ], "exact_answer": [ [ "ITGA4" ], [ "ITGB8" ], [ "ITGAL" ], [ "ICAM1" ] ], "type": "list", "id": "5c596ad686df2b9174000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1119, "text": "Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2, and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28067908", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 721, "text": "The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28067908", "endSection": "abstract" } ] }, { "body": "Which is the database of somatic mutations in normal cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30380071" ], "ideal_answer": [ "DSMNC is a database of somatic mutations in normal cells (http://dsmnc.big.ac.cn/) and provides a comprehensive catalogue of somatic SNVs in single cells from various normal tissues. In the current version, the database collected \u223c0.8 million SNVs accumulated in \u223c600 single normal cells (579 human cells and 39 mouse cells). The database interface supports the user-friendly capability of browsing and searching the SNVs and their annotation information." ], "exact_answer": [ "DSMNC", "Database of Somatic Mutations in Normal Cells" ], "type": "factoid", "id": "5c5b268986df2b9174000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "DSMNC: a database of somatic mutations in normal cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30380071", "endSection": "title" }, { "offsetInBeginSection": 396, "offsetInEndSection": 1440, "text": "Luckily, the recent development of single-cell genomics biotechnologies enables the screening and collection of the somatic mutations, especial single nucleotide variations (SNVs), occurring in normal cells. Here, we established DSMNC: a database of somatic mutations in normal cells (http://dsmnc.big.ac.cn/), which provides most comprehensive catalogue of somatic SNVs in single cells from various normal tissues. In the current version, the database collected \u223c0.8 million SNVs accumulated in \u223c600 single normal cells (579 human cells and 39 mouse cells). The database interface supports the user-friendly capability of browsing and searching the SNVs and their annotation information. DSMNC, which serves as a timely and valuable collection of somatic mutations in individual normal cells, has made it possible to analyze the burdens and signatures of somatic mutations in various types of heterogeneous normal cells. Therefore, DSMNC will significantly improve our understanding of the characteristics of somatic mutations in normal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30380071", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 866, "text": "Here, we established DSMNC: a database of somatic mutations in normal cells (http://dsmnc.big.ac.cn/), which provides most comprehensive catalogue of somatic SNVs in single cells from various normal tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30380071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "DSMNC: a database of somatic mutations in normal cells.Numerous non-inherited somatic mutations, distinct from those of germ-line origin, occur in somatic cells during DNA replication per cell-division. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30380071", "endSection": "title" }, { "offsetInBeginSection": 604, "offsetInEndSection": 811, "text": "Here, we established DSMNC: a database of somatic mutations in normal cells (http://dsmnc.big.ac.cn/), which provides most comprehensive catalogue of somatic SNVs in single cells from various normal tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30380071", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the Lonsurf pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28315543", "http://www.ncbi.nlm.nih.gov/pubmed/29177842", "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "http://www.ncbi.nlm.nih.gov/pubmed/26609205", "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "http://www.ncbi.nlm.nih.gov/pubmed/30350179", "http://www.ncbi.nlm.nih.gov/pubmed/27568360" ], "ideal_answer": [ "Lunsurf pill includes trifluridine and tipiracil. It is a novel form of chemotherapy for metastatic colorectal cancer." ], "exact_answer": [ [ "trifluridine" ], [ "tipiracil" ] ], "type": "list", "id": "5c72a9147c78d6947100006e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "The National Institute for Health and Care Excellence (NICE) invited Servier, the company manufacturing trifluridine and tipiracil (T/T; trade name: Lonsurf\u00ae), to submit evidence for the clinical and cost effectiveness of T/T compared with best supportive care (BSC) for metastatic colorectal cancer (third-line or later). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "PURPOSE: Trifluridine/tipiracil (FTD/TPI; TAS-102, Lonsurf\u00ae), a novel form of chemotherapy for metastatic colorectal cancer (mCRC), has shown clinical benefit in the global, phase III RECOURSE trial, regardless of patient age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30350179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "BACKGROUND: Trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 370, "text": "These AEs may affect patient adherence, particularly with completely oral regimens, such as trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), an antimetabolite agent for patients with mCRC refractory or intolerant to standard therapies.\u2029", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28315543", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 763, "text": "Trifluridine/tipiracil has recently been approved for the treatment of adult patients with metastatic colorectal cancer (mCRC) who are refractory to or are not considered candidates for, current standard chemotherapy and biological therapy in the EU and USA and in unresectable advanced or recurrent CRC in Japan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568360", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 352, "text": "TAS-102 (Lonsurf) is an oral fluoropyrimidine that is formed by the combination of 2 active drugs: trifluridine (a nucleoside analog) and tipiracil hydrochloride (a thymidine phosphorylase inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Evolocumab (Repatha) for patients with hypercholesterolemia whose condition has not been controlled by statins and other therapies; trifluridine/tipiracil (Lonsurf) for metastatic colorectal cancer; and blood coagulation factor VIII (Nuwiq) for adults and children with hemophilia A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26609205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf\u00ae tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Initial Evaluation of the Efficacy and Safety of Tablets Containing Trifluridine and Tipiracil Hydrochloride--Safety Measures Devised by a Multidisciplinary Team Including a Pharmaceutical Outpatient Clinic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "title" } ] }, { "body": "What is the association of epigallocatechin with the cardiovascular system?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27659729", "http://www.ncbi.nlm.nih.gov/pubmed/28871467", "http://www.ncbi.nlm.nih.gov/pubmed/29419571" ], "ideal_answer": [ "The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. EGCG was found to exhibit a wide range of therapeutic properties.", "Epigallocatechin gallate (EGCG), a bioactive ingredient of green tea, plays a protective role in the cardiovascular system." ], "type": "summary", "id": "5c5317e77e3cb0e231000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Epigallocatechin gallate (EGCG), a bioactive ingredient of green tea, plays a protective role in the cardiovascular system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28871467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Ameliorative Effect of Epigallocatechin Gallate on Cardiac Hypertrophy and Fibrosis in Aged Rats", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29419571", "endSection": "title" }, { "offsetInBeginSection": 92, "offsetInEndSection": 244, "text": " Epigallocatechin-3-O-gallate (EGCG), one of the active compounds in green tea, has anti-oxidant, anti-inflammatory and vascular protective properties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27659729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27659729", "endSection": "title" } ] }, { "body": "What is the mechanism of action of tucatinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29772459", "http://www.ncbi.nlm.nih.gov/pubmed/28923217", "http://www.ncbi.nlm.nih.gov/pubmed/29804905", "http://www.ncbi.nlm.nih.gov/pubmed/29955792" ], "ideal_answer": [ "Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer." ], "type": "summary", "id": "5c6641ea7c78d69471000016", "snippets": [ { "offsetInBeginSection": 1099, "offsetInEndSection": 1331, "text": "In this article we review the role of currently available or investigational HER2 tyrosine kinase inhibitors: lapatinib, neratinib, afatinib and tucatinib in the treatment of brain metastases in HER2-positive breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29772459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND: Tucatinib is a potent and selective oral HER2 tyrosine kinase inhibitor, with the potential to provide a well tolerated new treatment option for patients whose disease has progressed on currently available therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804905", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 944, "text": "The utility of human epidermal growth factor 2 (HER2)-directed therapies-lapatinib, ado-trastuzumab emtansine (T-DM1), neratinib and tucatinib-is also being studied in this setting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28923217", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 359, "text": "Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29955792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND\nTucatinib is a potent and selective oral HER2 tyrosine kinase inhibitor, with the potential to provide a well tolerated new treatment option for patients whose disease has progressed on currently available therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804905", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 358, "text": "Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29955792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND Tucatinib is a potent and selective oral HER2 tyrosine kinase inhibitor, with the potential to provide a well tolerated new treatment option for patients whose disease has progressed on currently available therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29804905", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 943, "text": "The utility of human epidermal growth factor 2 (HER2)-directed therapies-lapatinib, ado-trastuzumab emtansine (T-DM1), neratinib and tucatinib-is also being studied in this setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28923217", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 885, "text": "Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer.
Objective: To determine the maximum tolerated dosage of tucatinib in combination with T-DM1 in the treatment of patients with ERBB2/HER2-positive metastatic breast cancer with and without brain metastases.
Design, Setting, and Participants: In this phase 1b open-label, multicenter, clinical trial, 57 participants enrolled between January 22, 2014, and June 22, 2015, were 18 years of age or older with ERBB2/HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29955792", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by a drug Lorlatinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29400604", "http://www.ncbi.nlm.nih.gov/pubmed/29376144", "http://www.ncbi.nlm.nih.gov/pubmed/30394941", "http://www.ncbi.nlm.nih.gov/pubmed/29458783", "http://www.ncbi.nlm.nih.gov/pubmed/30322862", "http://www.ncbi.nlm.nih.gov/pubmed/29744867", "http://www.ncbi.nlm.nih.gov/pubmed/29067878", "http://www.ncbi.nlm.nih.gov/pubmed/30174447", "http://www.ncbi.nlm.nih.gov/pubmed/29373100", "http://www.ncbi.nlm.nih.gov/pubmed/28594000", "http://www.ncbi.nlm.nih.gov/pubmed/30413378", "http://www.ncbi.nlm.nih.gov/pubmed/29174221" ], "ideal_answer": [ "Lorlatinib is anaplastic lymphoma kinase inhibitor." ], "exact_answer": [ "anaplastic lymphoma kinase" ], "type": "factoid", "id": "5c72ade07c78d69471000070", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "PURPOSE OF REVIEW: We describe recent developments in the rapidly evolving field of anaplastic lymphoma kinase-targeting agents.RECENT FINDINGS: Five targeted drugs are currently available in the clinic via regular approval or named patient programs, including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 661, "text": "IMPORTANCE: The identification of anaplastic lymphoma kinase (ALK) rearrangements in 2-5% of non-small cell lung cancer (NSCLC) patients led to the rapid clinical development of its oral tyrosine kinase inhibitor (TKI). Crizotinib was the first ALK inhibitor approved and utilised in the treatment of ALK+ NSCLC patients in the second line setting first and subsequently in the first line one. Since then many other ALK inhibitors have been developed (ceritinib, alectinib, brigatinib, lorlatinib,etc) and the treatment paradigm of these patients has considerably drifted. The questions regarding their treatment at progression remains unanswered at the moment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29458783", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 728, "text": "RESULTS: ALK T1151Sins mutation was detected when the patient developed resistance to ceritinib, and undetectable when she responded to lorlatinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29400604", "endSection": "abstract" }, { "offsetInBeginSection": 1372, "offsetInEndSection": 1534, "text": "ALK G1202R, the most frequent plasma mutation detected after progression on a second-generation TKI, was consistently suppressed during treatment with lorlatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29376144", "endSection": "abstract" }, { "offsetInBeginSection": 1335, "offsetInEndSection": 1552, "text": "Among patients treated with the third-generation ALK TKI lorlatinib, variant 3 was associated with a significantly longer progression-free survival than variant 1 (hazard ratio, 0.31; 95% CI, 0.12 to 0.79; P = .011). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29373100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Brain Penetration of the ROS1/ALK Inhibitor Lorlatinib Confirmed by PET.F-labeling strategies to synthesize isotopologs of lorlatinib (PF-06463922) which is undergoing phase III clinical trial investigations for treatment of non-small-cell lung cancers with specific molecular alterations. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29067878", "endSection": "title" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1129, "text": "In addition, further functional in vitro studies demonstrated that ALK harboring the T1151Sins mutation, while conferring resistance to ceritinib, was inhibited by lorlatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29400604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Lorlatinib (PF-06463922) is a promising oral anaplastic lymphoma kinase (ALK) and ROS1 inhibitor currently in Phase III clinical trials for treatment of non-small-cell lung cancer (NSCLC) containing an ALK rearrangement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29744867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "P-glycoprotein (MDR1/ABCB1) restricts brain accumulation and cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK/ROS1 inhibitor lorlatinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29744867", "endSection": "title" }, { "offsetInBeginSection": 118, "offsetInEndSection": 232, "text": "Lorlatinib is a third generation ALK inhibitor that inhibits most ALK mutants resistant to current ALK inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30322862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Lorlatinib (PF-06463922) is a next-generation small-molecule inhibitor of the orphan receptor tyrosine kinase c-ros oncogene 1 (ROS1), which has a kinase domain that is physiologically related to anaplastic lymphoma kinase (ALK), and is undergoing Phase I/II clinical trial investigations for non-small cell lung cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28594000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND\nLorlatinib is a potent, brain-penetrant, third-generation inhibitor of ALK and ROS1 tyrosine kinases with broad coverage of ALK mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413378", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1038, "text": "The next-generation ALK inhibitor lorlatinib (PF-06463922) has therefore been developed to inhibit resistant ALK mutations, including ALK G1202R, and to penetrate the blood-brain barrier.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30174447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BACKGROUND Lorlatinib is a potent, brain-penetrant, third-generation inhibitor of ALK and ROS1 tyrosine kinases with broad coverage of ALK mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413378", "endSection": "abstract" } ] }, { "body": "What periodontal disease associated bacteria is also associated with Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22546352", "http://www.ncbi.nlm.nih.gov/pubmed/29046054", "http://www.ncbi.nlm.nih.gov/pubmed/28294067", "http://www.ncbi.nlm.nih.gov/pubmed/29249963" ], "ideal_answer": [ "Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer's disease (AD).", "Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD." ], "exact_answer": [ "Porphyromonas gingivalis" ], "type": "factoid", "id": "5c53191a7e3cb0e231000016", "snippets": [ { "offsetInBeginSection": 1229, "offsetInEndSection": 1471, "text": "Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28294067", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 527, "text": " working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis, a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29249963", "endSection": "abstract" } ] }, { "body": "Is deletion at 6q24.2-26 associated with longer survival of patients with high-grade serous ovarian carcinoma (HGSOCs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "http://www.ncbi.nlm.nih.gov/pubmed/26463438" ], "ideal_answer": [ "Yes. Loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors. The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019)." ], "exact_answer": "yes", "type": "yesno", "id": "5c5b52731a4c55d80b000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "title" }, { "offsetInBeginSection": 602, "offsetInEndSection": 1882, "text": "We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "abstract" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1882, "text": "Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "OBJECTIVE\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "OBJECTIVE We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1886, "text": "Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 508, "text": "OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.
METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" } ] }, { "body": "How does the Cholera toxin enter a cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26405107", "http://www.ncbi.nlm.nih.gov/pubmed/27914621", "http://www.ncbi.nlm.nih.gov/pubmed/26478842" ], "ideal_answer": [ "Cholera toxin (CT), which is secreted by V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells." ], "exact_answer": [ "Cholera toxin (CT) can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells." ], "type": "factoid", "id": "5c7813f57c78d694710000b0", "snippets": [ { "offsetInBeginSection": 258, "offsetInEndSection": 461, "text": "Cholera toxin (CT), which is secreted by V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26405107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "The five B-subunits (CTB5) of the Vibrio cholerae (cholera) toxin can bind to the intestinal cell surface so the entire AB5 toxin can enter the cell. Simultaneous binding can occur on more than one of the monosialotetrahexosylganglioside (GM1) units present on the cell surface. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26478842", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 549, "text": "we test the role of glycolipid crosslinking as a raft targeting and ordering mechanism using the well-studied raft marker cholera toxin B pentamer (CTxB) that binds up to five GM1 glycosphingolipids to enter host cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27914621", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of Lurbinectedin.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30153704", "http://www.ncbi.nlm.nih.gov/pubmed/29883879", "http://www.ncbi.nlm.nih.gov/pubmed/28683469", "http://www.ncbi.nlm.nih.gov/pubmed/30090974", "http://www.ncbi.nlm.nih.gov/pubmed/27630271", "http://www.ncbi.nlm.nih.gov/pubmed/30240327", "http://www.ncbi.nlm.nih.gov/pubmed/30362375" ], "ideal_answer": [ "Lurbinectedin is a novel highly selective inhibitor of RNA polymerase II triggering caspase-dependent apoptosis of cancerous cells. It inhibits active transcription of protein-coding genes, causing DNA-break accumulation, apoptosis and modulation of the tumor microenvironment." ], "type": "summary", "id": "5c72b4897c78d69471000071", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Lurbinectedin is a novel highly selective inhibitor of RNA polymerase II triggering caspase-dependent apoptosis of cancerous cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29883879", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 229, "text": "Lurbinectedin is a next-generation minor groove binder with preclinical activity against myeloid leukemia cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30153704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "BACKGROUND AND OBJECTIVES: Lurbinectedin is an inhibitor of RNA polymerase II currently under clinical development for intravenous administration as a single agent and in combination with other anti-tumor agents for the treatment of several tumor types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30090974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "PURPOSE: This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30240327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Lurbinectedin is an inhibitor of active transcription of protein-coding genes, causing DNA-break accumulation, apoptosis and modulation of the tumor microenvironment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30362375", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 339, "text": "Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Lurbinectedin Specifically Triggers the Degradation of Phosphorylated RNA Polymerase II and the Formation of DNA Breaks in Cancer Cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27630271", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Lurbinectedin is a novel highly selective inhibitor of RNA polymerase II triggering caspase-dependent apoptosis of cancerous cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29883879", "endSection": "abstract" } ] }, { "body": "Can mogamulizumab be used for the treatment of cutaneous T-cell lymphoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29298770" ], "ideal_answer": [ "Yes, mogamulizumab can be used for the treatment of cutaneous T-cell lymphoma." ], "exact_answer": "yes", "type": "yesno", "id": "5c65484ee842deac6700001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "In the large international phase III MAVORIC trial, patients with previously treated cutaneous T-cell lymphoma who received the anti-CCR4 monoclonal antibody mogamulizumab experienced significantly longer progression-free survival and higher response rates, as well as better quality of life, than those who received vorinostat, a standard therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29298770", "endSection": "abstract" } ] }, { "body": "Which enzymes are inhibited by Duvelisib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30067771", "http://www.ncbi.nlm.nih.gov/pubmed/30033575", "http://www.ncbi.nlm.nih.gov/pubmed/30094870", "http://www.ncbi.nlm.nih.gov/pubmed/29522278", "http://www.ncbi.nlm.nih.gov/pubmed/29191916", "http://www.ncbi.nlm.nih.gov/pubmed/28388280", "http://www.ncbi.nlm.nih.gov/pubmed/29233821", "http://www.ncbi.nlm.nih.gov/pubmed/27174919", "http://www.ncbi.nlm.nih.gov/pubmed/25912635", "http://www.ncbi.nlm.nih.gov/pubmed/28017967", "http://www.ncbi.nlm.nih.gov/pubmed/29479062" ], "ideal_answer": [ "Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-\u03b4 (PI3K-\u03b4) and PI3K-\u03b3 in late-stage clinical development for hematologic malignancy treatment." ], "exact_answer": [ [ "phosphoinositide 3-kinase-\u03b4" ], [ "phosphoinositide 3-kinase-\u03b3" ] ], "type": "list", "id": "5c72b6be7c78d69471000072", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Duvelisib (IPI-145) is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)-\u03b4/\u03b3 isoforms currently in clinical development. PI3K-\u03b4/\u03b3 inhibition may directly inhibit malignant T-cell growth, making duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Activity of the PI3K-\u03b4,\u03b3 inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233821", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Duvelisib, a novel oral dual inhibitor of PI3K-\u03b4,\u03b3, is clinically active in advanced hematologic malignancies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29191916", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-\u03b4 (PI3K-\u03b4) and PI3K-\u03b3 in late-stage clinical development for hematologic malignancy treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29191916", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 699, "text": "We observed that pharmaceutical PI3K\u03b3 inhibition with CZC24832 significantly impaired CLL\u00a0cell migration, while dual PI3K\u03b4/\u03b3 inhibitor duvelisib had a greater impact than single isoform-selective inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29479062", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 433, "text": "An oral dual inhibitor of PI3K\u03b3 and PI3K\u03b4, duvelisib, is in clinical trials for the treatment of lymphoid malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Duvelisib, an oral dual PI3K-\u03b4, \u03b3 inhibitor, shows clinical activity in indolent non-Hodgkin lymphoma in a phase 1 study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30033575", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Duvelisib (IPI-145) is an oral dual inhibitor of phosphoinositide-3-kinase (PI3K)-\u03b4 and -\u03b3 in clinical development for the treatment of hematologic malignancies, including indolent non-Hodgkin lymphoma (iNHL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30033575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Duvelisib, an oral dual PI3K-\u03b4,\u03b3 inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30094870", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-\u03b4 and -\u03b3, was evaluated in a Phase 1 study in advanced hematologic malignancies, which included expansion cohorts in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and treatment-na\u00efve (TN) CLL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30094870", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1234, "text": "Expert opinion: Duvelisib targets the PI3K \u03b4 isoform, which is necessary for cell proliferation and survival, and \u03b3 isoform, which is critical for cytokine signaling and pro-inflammatory responses from the microenvironment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28388280", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 832, "text": "The functions of these individual catalytic enzymes have not been fully resolved in AML, therefore using the PI3K p110\u03b4 and p110\u03b3-targeted inhibitor IPI-145 (duvelisib) and specific p110\u03b4 and p110\u03b3 shRNA, we analysed the role of these two p110 subunits in human AML blast survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27174919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The phosphoinositide-3 kinase (PI3K)-\u03b4,\u03b3 inhibitor, duvelisib shows preclinical synergy with multiple targeted therapies in hematologic malignancies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30067771", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Duvelisib is an orally active dual inhibitor of PI3K-\u03b4 and PI3K-\u03b3 in clinical development in hematologic malignancies (HM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30067771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Duvelisib (IPI-145) is an oral dual inhibitor of phosphoinositide-3-kinase (PI3K)-\u03b4 and -\u03b3 in clinical development for the treatment of hematologic malignancies, including indolent non-Hodgkin lymphoma (iNHL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30033575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Duvelisib (IPI-145) is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)-\u03b4/\u03b3 isoforms currently in clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233821", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 306, "text": "PI3K-\u03b4/\u03b3 inhibition may directly inhibit malignant T-cell growth, making duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233821", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 718, "text": "The functions of these individual catalytic enzymes have not been fully resolved in AML, therefore using the PI3K p110\u03b4 and p110\u03b3-targeted inhibitor IPI-145 (duvelisib) and specific p110\u03b4 and p110\u03b3 shRNA, we analysed the role of these two p110 subunits in human AML blast survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27174919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Duvelisib: a phosphoinositide-3 kinase \u03b4/\u03b3 inhibitor for chronic lymphocytic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28388280", "endSection": "title" }, { "offsetInBeginSection": 466, "offsetInEndSection": 617, "text": "Duvelisib, a PI3K \u03b4/\u03b3 dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28388280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Duvelisib, an oral dual inhibitor of PI3K-\u03b4 and PI3K-\u03b3, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28017967", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1148, "text": "Expert opinion: Duvelisib targets the PI3K \u03b4 isoform, which is necessary for cell proliferation and survival, and \u03b3 isoform, which is critical for cytokine signaling and pro-inflammatory responses from the microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28388280", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 523, "text": "The purely PI3K-\u03b4-selective inhibitor idelalisib was compared to copanlisib (BAY 80-6946) and duvelisib (IPI-145), with isoform target profiles that additionally include PI3K-\u03b1 or PI3K-\u03b3, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25912635", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 601, "text": "In this study, we evaluated how duvelisib affects the activity of the PI3K/Akt signaling pathway and if it has antitumor effects in EBV-associated lymphoma cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522278", "endSection": "abstract" } ] }, { "body": "List search engines used in proteomics.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28960077", "http://www.ncbi.nlm.nih.gov/pubmed/29216772", "http://www.ncbi.nlm.nih.gov/pubmed/29993281", "http://www.ncbi.nlm.nih.gov/pubmed/27498275" ], "ideal_answer": [ "Mascot\nX!Tandem\nMS-GF\nMS Amanda \nMyriMatch\nComet\nTide\nAndromeda\nOMSSA" ], "exact_answer": [ [ "Mascot" ], [ "X!Tandem" ], [ "MS-GF" ], [ "MS Amanda" ], [ "MyriMatch" ], [ "Comet" ], [ "Tide" ], [ "Andromeda" ], [ "OMSSA" ] ], "type": "list", "id": "5c78174b7c78d694710000b1", "snippets": [ { "offsetInBeginSection": 368, "offsetInEndSection": 728, "text": "We compared the contribution of each of the eight search engines (X!Tandem, MS-GF[Formula: see text], MS Amanda, MyriMatch, Comet, Tide, Andromeda, and OMSSA) integrated in an open-source graphical user interface SearchGUI ( http://searchgui.googlecode.com ) into total result of proteoforms identification and optimized set of engines working simultaneously. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29216772", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 678, "text": " This software is also highly compatible with the identification and quantification results of various frequently used search engines, such as MaxQuant, Proteome Discoverer, or Mascot. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29993281", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 704, "text": " database search engines: Mascot, X!Tandem, and MS-GF+.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498275", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 638, "text": "applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960077", "endSection": "abstract" } ] }, { "body": "Is avelumab effective for bladder cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29069302", "http://www.ncbi.nlm.nih.gov/pubmed/29606979", "http://www.ncbi.nlm.nih.gov/pubmed/28864844", "http://www.ncbi.nlm.nih.gov/pubmed/28214651", "http://www.ncbi.nlm.nih.gov/pubmed/29644490", "http://www.ncbi.nlm.nih.gov/pubmed/29416316", "http://www.ncbi.nlm.nih.gov/pubmed/29540084", "http://www.ncbi.nlm.nih.gov/pubmed/29784744", "http://www.ncbi.nlm.nih.gov/pubmed/28982750", "http://www.ncbi.nlm.nih.gov/pubmed/29103968", "http://www.ncbi.nlm.nih.gov/pubmed/28493171" ], "ideal_answer": [ "Yes, avelumab is effective treatment of bladder cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5c72ba807c78d69471000076", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29103968", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 964, "text": "Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069302", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 779, "text": "The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29416316", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 810, "text": "Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606979", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 717, "text": "RECENT FINDINGS: Since May 2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Avelumab for the treatment of urothelial cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540084", "endSection": "title" }, { "offsetInBeginSection": 580, "offsetInEndSection": 924, "text": "Avelumab, a PD-1 ligand (PD-L1) inhibitor, is currently being investigated for the treatment of UC. Areas covered: This article will review the pharmacological characteristics of avelumab, the efficacy studies which led to its approval, its safety profile, as well as its place within the management of urothelial carcinoma with immunotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540084", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1193, "text": "Expert commentary: Avelumab has shown promising antitumor activity and a manageable safety profile in patients with UC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540084", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1280, "text": "Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, durvalumab, and avelumab all have positive results for this indication, and approvals are anticipated in the near future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28214651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28982750", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1216, "text": "Atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab are promising PD-1/PD-L1 blockade drugs under investigation that will redefine the standard of care for bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493171", "endSection": "abstract" }, { "offsetInBeginSection": 2200, "offsetInEndSection": 2493, "text": "Monoclonal antibodies that target programmed cell death protein 1 (PD-1), including Nivolumab and Pembrolizumab, and its ligand, PD-L1, including Atezolizumab, Durvalumab, Avelumab, have all been investigated and approved in the setting of metastatic refractory urothelial cancer (Gupta et al.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28864844", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 963, "text": "Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069302", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 504, "text": "Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29784744", "endSection": "abstract" } ] }, { "body": "Is cabozantinib effective for Hepatocellular Carcinoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27638856", "http://www.ncbi.nlm.nih.gov/pubmed/29505843", "http://www.ncbi.nlm.nih.gov/pubmed/29059635", "http://www.ncbi.nlm.nih.gov/pubmed/29807383", "http://www.ncbi.nlm.nih.gov/pubmed/30308081", "http://www.ncbi.nlm.nih.gov/pubmed/29283440", "http://www.ncbi.nlm.nih.gov/pubmed/30317696", "http://www.ncbi.nlm.nih.gov/pubmed/28426123", "http://www.ncbi.nlm.nih.gov/pubmed/30039640", "http://www.ncbi.nlm.nih.gov/pubmed/30087805", "http://www.ncbi.nlm.nih.gov/pubmed/29253194", "http://www.ncbi.nlm.nih.gov/pubmed/28703624", "http://www.ncbi.nlm.nih.gov/pubmed/29913090", "http://www.ncbi.nlm.nih.gov/pubmed/29783126", "http://www.ncbi.nlm.nih.gov/pubmed/24700742", "http://www.ncbi.nlm.nih.gov/pubmed/28862760", "http://www.ncbi.nlm.nih.gov/pubmed/29972759" ], "ideal_answer": [ "Yes, cabozantinib is approved as second line agent for treatment of Hepatocellular Carcinoma.", "Yes, cabozantinib effective for hepatocellular carcinoma. Cabozantinib is useful second-line therapy after the failure of sorafenib." ], "exact_answer": "yes", "type": "yesno", "id": "5c6b7a9e7c78d69471000029", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 373, "text": "However, clinical trials of nonselective kinase inhibitors with c-Met activity (tivantinib, cabozantinib, foretinib, and golvatinib) in patients with HCC have failed so far to demonstrate significant efficacy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28862760", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 604, "text": "Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29283440", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 964, "text": "More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253194", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 509, "text": "Positive results in recent phase III clinical trials have confirmed the high value of anti-angiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29505843", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 488, "text": "More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29783126", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1459, "text": "The rapidly changing treatment landscape due to the emergence of new treatment options (sorafenib and lenvatinib equally effective in first line; regorafenib, cabozantinib, and ramucirumab showing OS benefit in second line with nivolumab approved by the FDA based on response rate) underscores the importance of re-assessing the role of the first approved systemic agent in HCC, sorafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29783126", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 917, "text": "Positive phase III-study data have been published for lenvatinib as first-line and cabozantinib as second-line therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29807383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "BACKGROUND: Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "abstract" }, { "offsetInBeginSection": 1925, "offsetInEndSection": 2119, "text": "CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 971, "text": "Expert opinion: Based on favorable phase III clinical trial data, sorafenib and lenvatinib are considered promising agents for HCC as first-line systemic chemotherapy. Moreover, regorafenib and cabozantinib are useful second-line therapies after the failure of sorafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29913090", "endSection": "abstract" }, { "offsetInBeginSection": 1925, "offsetInEndSection": 2120, "text": "CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "title" }, { "offsetInBeginSection": 1899, "offsetInEndSection": 2080, "text": "Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1559, "text": "Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "abstract" }, { "offsetInBeginSection": 1704, "offsetInEndSection": 2159, "text": "The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).
CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "abstract" }, { "offsetInBeginSection": 1931, "offsetInEndSection": 2124, "text": "CONCLUSIONS Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29972759", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1399, "text": "CONCLUSIONS The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30039640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments such as lenvatinib in first-line treatment and regorafenib, cabozantinib and ramucirumab in second-line treatment due to their benefits in terms of overall survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30317696", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1527, "text": "Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "BACKGROUND: The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30039640", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1443, "text": "We also elaborate the unmet need of biomarkers to guide treatment decisions and discuss the emerging field of immunotherapy in hepatocellular carcinoma.
CONCLUSIONS: The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30039640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Cabozantinib in the treatment of hepatocellular carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28703624", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30039640", "endSection": "abstract" } ] }, { "body": "De novo mutations in which novel genes are involved in systemic lupus erythematosus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29177435" ], "ideal_answer": [ "DNMT3A, PRKCD, and C1QTNF4." ], "exact_answer": [ [ "DNMT3A" ], [ "PRKCD" ], [ "C1QTNF4" ] ], "type": "list", "id": "5c62a276e842deac6700000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "De novo mutations implicate novel genes in systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177435", "endSection": "title" }, { "offsetInBeginSection": 192, "offsetInEndSection": 1756, "text": " Rare variant associations, expected to explain far less of the heritability, may be enriched in core disease genes and thus will be instrumental in the understanding of complex disease pathogenesis and their potential therapeutic targets. Here, using complementary whole-exome sequencing, high-density imputation, and in vitro cellular assays, we identify candidate core genes in the pathogenesis of systemic lupus erythematosus (SLE). Using extreme-phenotype sampling, we sequenced the exomes of 30 SLE parent-affected-offspring trios and identified 14 genes with missense de novo mutations (DNM), none of which are within the\u2009>80 SLE susceptibility loci implicated through genome-wide association studies. In a follow-up cohort of 10, 995 individuals of matched European ancestry, we imputed genotype data to the density of the combined UK10K-1000 genomes Phase III reference panel across the 14 candidate genes. Gene-level analyses indicate three functional candidates: DNMT3A, PRKCD, and C1QTNF4. We identify a burden of rare variants across PRKCD associated with SLE risk (P\u2009=\u20090.0028), and across DNMT3A associated with two severe disease prognosis sub-phenotypes (P\u2009=\u20090.0005 and P\u2009=\u20090.0033). We further characterise the TNF-dependent functions of the third candidate gene C1QTNF4 on NF-\u03baB activation and apoptosis, which are inhibited by the p.His198Gln DNM. Our results identify three novel genes in SLE susceptibility and support extreme-phenotype sampling and DNM gene discovery to aid the search for core disease genes implicated through rare variation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177435", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1390, "text": "We identify a burden of rare variants across PRKCD associated with SLE risk (P\u2009=\u20090.0028), and across DNMT3A associated with two severe disease prognosis sub-phenotypes (P\u2009=\u20090.0005 and P\u2009=\u20090.0033).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177435", "endSection": "abstract" } ] }, { "body": "Is there a link between BCL11B haploinsufficiency and syndromic neurodevelopmental delay?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29985992" ], "ideal_answer": [ "No. Mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay." ], "exact_answer": "no", "type": "yesno", "id": "5c5839e707647bbc4b00001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29985992", "endSection": "title" }, { "offsetInBeginSection": 427, "offsetInEndSection": 2177, "text": "Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29985992", "endSection": "abstract" }, { "offsetInBeginSection": 1951, "offsetInEndSection": 2130, "text": "Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29985992", "endSection": "abstract" }, { "offsetInBeginSection": 1838, "offsetInEndSection": 2017, "text": "Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29985992", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of motolimod?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29345064", "http://www.ncbi.nlm.nih.gov/pubmed/27702821", "http://www.ncbi.nlm.nih.gov/pubmed/29931076", "http://www.ncbi.nlm.nih.gov/pubmed/28453702", "http://www.ncbi.nlm.nih.gov/pubmed/26928328", "http://www.ncbi.nlm.nih.gov/pubmed/27467937", "http://www.ncbi.nlm.nih.gov/pubmed/28485332", "http://www.ncbi.nlm.nih.gov/pubmed/27810904", "http://www.ncbi.nlm.nih.gov/pubmed/26152744" ], "ideal_answer": [ "Motolimod is the toll-like receptor 8 (TLR8) agonist that stimulates innate and adaptive immunity." ], "type": "summary", "id": "5c663e277c78d69471000015", "snippets": [ { "offsetInBeginSection": 275, "offsetInEndSection": 393, "text": "We investigated expression of TLR8 on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29345064", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 224, "text": "The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29931076", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 451, "text": "We sought to develop a rational combination of motolimod-a novel Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses in humans but diminished responses in mice-with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27702821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Phase Ib Trial of the Toll-like Receptor 8 Agonist, Motolimod (VTX-2337), Combined with Cetuximab in Patients with Recurrent or Metastatic SCCHN.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810904", "endSection": "title" }, { "offsetInBeginSection": 206, "offsetInEndSection": 342, "text": "Motolimod (VTX-2337), a selective small-molecule agonist of TLR8, stimulates natural killer (NK) cells, dendritic cells, and monocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 369, "text": "Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Motolimod effectively drives immune activation in advanced cancer patients.A novel approach to immunotherapy is the activation of toll-like receptor 8 (TLR8). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27467937", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Late-Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152744", "endSection": "title" }, { "offsetInBeginSection": 161, "offsetInEndSection": 1134, "text": "We sought to develop a rational combination of motolimod-a novel Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses in humans but diminished responses in mice-with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.Experimental Design: We followed an integrative pharmacologic approach including healthy human volunteers, non-human primates, NSG-HIS (\"humanized immune system\") mice reconstituted with human CD34+ cells, and patients with cancer to test the effects of motolimod and to assess the combination of motolimod with PLD for the treatment of ovarian cancer.Results: The pharmacodynamic effects of motolimod monotherapy in NSG-HIS mice closely mimicked those in non-human primates and healthy human subjects, whereas the effects of the motolimod/PLD combination in tumor-bearing NSG-HIS mice closely mimicked those in patients with ovarian cancer treated in a phase Ib trial (NCT01294293).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27702821", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 341, "text": "Motolimod (VTX-2337), a selective small-molecule agonist of TLR8, stimulates natural killer (NK) cells, dendritic cells, and monocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810904", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 437, "text": "The activity of motolimod (VTX-2337), a potent and selective Toll-like receptor 8 (TLR8) agonist, was therefore assessed in the context of advanced, late-stage cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152744", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1571, "text": "CONCLUSIONS\nLate-stage cancer patients are highly sensitive to TLR8 activation by motolimod.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152744", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 831, "text": "Translational studies in cynomolgus monkeys elucidated the activity of motolimod on an intact immune system, identified biomarkers of TLR8 activation, and defined the relationship between the pharmacokinetic and pharmacodynamic (PK/PD) response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "UNLABELLED\nVTX-2337 (USAN: motolimod) is a selective toll-like receptor 8 (TLR8) agonist, which is in clinical development as an immunotherapy for multiple oncology indications, including squamous cell carcinoma of the head and neck (SCCHN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26928328", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 236, "text": "Motolimod, a selective TLR8 agonist can act in concert with approved immunotherapies to sensitize T cells and augment natural killer (NK) cell function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27467937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "UNLABELLED VTX-2337 (USAN: motolimod) is a selective toll-like receptor 8 (TLR8) agonist, which is in clinical development as an immunotherapy for multiple oncology indications, including squamous cell carcinoma of the head and neck (SCCHN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26928328", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 1058, "text": "Immunotherapy represents an attractive treatment option for R/M HNSCC, with encouraging preliminary data from studies involving immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) and toll-like receptor agonists (e.g., motolimod).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28485332", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 668, "text": "The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity.
Objective: To determine whether motolimod improves outcomes for R/M SCCHN when combined with standard therapy.
Design, Setting, and Participants: The Active8 study was a multicenter, randomized, double-blind, placebo-controlled clinical trial enrolling adult patients (age \u226518 years) with histologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx between October 2013 and August 2015.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29931076", "endSection": "abstract" }, { "offsetInBeginSection": 1377, "offsetInEndSection": 1606, "text": "In addition, the PK/PD response in cancer patients closely aligned with the activity of motolimod seen in healthy volunteers.
CONCLUSIONS: Late-stage cancer patients are highly sensitive to TLR8 activation by motolimod.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152744", "endSection": "abstract" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1517, "text": "Late-stage cancer patients are highly sensitive to TLR8 activation by motolimod.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152744", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 1132, "text": "We sought to develop a rational combination of motolimod-a novel Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses in humans but diminished responses in mice-with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.Experimental Design: We followed an integrative pharmacologic approach including healthy human volunteers, non-human primates, NSG-HIS (humanized immune system) mice reconstituted with human CD34+ cells, and patients with cancer to test the effects of motolimod and to assess the combination of motolimod with PLD for the treatment of ovarian cancer.Results: The pharmacodynamic effects of motolimod monotherapy in NSG-HIS mice closely mimicked those in non-human primates and healthy human subjects, whereas the effects of the motolimod/PLD combination in tumor-bearing NSG-HIS mice closely mimicked those in patients with ovarian cancer treated in a phase Ib trial (NCT01294293).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27702821", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 429, "text": "The activity of motolimod (VTX-2337), a potent and selective Toll-like receptor 8 (TLR8) agonist, was therefore assessed in the context of advanced, late-stage cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26152744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453702", "endSection": "abstract" } ] }, { "body": "Is Lasmiditan effective for migraine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29488143", "http://www.ncbi.nlm.nih.gov/pubmed/29352859", "http://www.ncbi.nlm.nih.gov/pubmed/22430431", "http://www.ncbi.nlm.nih.gov/pubmed/22459549", "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "http://www.ncbi.nlm.nih.gov/pubmed/29563831", "http://www.ncbi.nlm.nih.gov/pubmed/20855362", "http://www.ncbi.nlm.nih.gov/pubmed/28103158", "http://www.ncbi.nlm.nih.gov/pubmed/30323656", "http://www.ncbi.nlm.nih.gov/pubmed/29098075" ], "ideal_answer": [ "Yes, Lasmiditan is effective for treatment of migraine. This has been demonstrated in clinical trials." ], "exact_answer": "yes", "type": "yesno", "id": "5c6f6ae37c78d69471000054", "snippets": [ { "offsetInBeginSection": 1191, "offsetInEndSection": 1370, "text": "Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29352859", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1634, "text": "Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29488143", "endSection": "abstract" }, { "offsetInBeginSection": 1136, "offsetInEndSection": 1255, "text": "Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29563831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323656", "endSection": "title" }, { "offsetInBeginSection": 523, "offsetInEndSection": 951, "text": "Lasmiditan, a highly selective 5-HT1F agonist, has completed two Phase III randomized, double blind, placebo-controlled clinical trials, with a third - a long-term, open-label safety study - still underway. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "endSection": "title" }, { "offsetInBeginSection": 640, "offsetInEndSection": 1192, "text": "Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, p< 0.001), similar to those dosed with lasmiditan 100 mg (28.2%; OR 2.2, 95% CI 1.6-3.0, p< 0.001). Furthermore, compared with those dosed with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; OR 1.6, 95% CI 1.3-2.1, p< 0.001) and lasmiditan 100 mg (40.9%; OR 1.7, 95% CI, 1.3-2.2, p< 0.001) were free of their MBS at 2 hours after dosing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1431, "text": "CONCLUSIONS: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "endSection": "abstract" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1697, "text": "CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1350, "text": "For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430431", "endSection": "abstract" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1584, "text": "While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20855362", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323656", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "BACKGROUND\nLasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22459549", "endSection": "abstract" }, { "offsetInBeginSection": 2485, "offsetInEndSection": 2582, "text": "INTERPRETATION\nOral lasmiditan seems to be safe and effective in the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22459549", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1124, "text": "The 5-HT1F receptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28103158", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1200, "text": "For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430431", "endSection": "title" }, { "offsetInBeginSection": 647, "offsetInEndSection": 1016, "text": "Within the past few years, new and promising drugs such as more specific 5-HT 1F receptor agonists (that is, lasmiditan) and monoclonal calcitonin gene-related peptide (CGRP) receptor antibodies entered advanced development phases while non-invasive neuromodulatory approaches were suggested to be potentially effective as non-pharmaceutical interventions for migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29098075", "endSection": "abstract" }, { "offsetInBeginSection": 1484, "offsetInEndSection": 1706, "text": "CLASSIFICATION OF EVIDENCE\nThis study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "BACKGROUND Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22459549", "endSection": "abstract" }, { "offsetInBeginSection": 2485, "offsetInEndSection": 2582, "text": "INTERPRETATION Oral lasmiditan seems to be safe and effective in the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22459549", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 951, "text": "Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323656", "endSection": "abstract" }, { "offsetInBeginSection": 2310, "offsetInEndSection": 2510, "text": "The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20855362", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 1346, "text": "Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6,
CONCLUSIONS: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors.
CLINICALTRIALSGOV IDENTIFIER: NCT02439320.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "endSection": "abstract" }, { "offsetInBeginSection": 2389, "offsetInEndSection": 2617, "text": "The most common adverse events were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and somnolence.
INTERPRETATION: Oral lasmiditan seems to be safe and effective in the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22459549", "endSection": "abstract" }, { "offsetInBeginSection": 2012, "offsetInEndSection": 2238, "text": "Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan.
CONCLUSIONS: At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20855362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22459549", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1206, "text": "For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430431", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1610, "text": "This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30446595", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1440, "text": "While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22430431", "endSection": "abstract" } ] }, { "body": "List drugs included in the TRIUMEQ pill.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29105160", "http://www.ncbi.nlm.nih.gov/pubmed/28748198", "http://www.ncbi.nlm.nih.gov/pubmed/29533918", "http://www.ncbi.nlm.nih.gov/pubmed/27912079", "http://www.ncbi.nlm.nih.gov/pubmed/27530904", "http://www.ncbi.nlm.nih.gov/pubmed/29059031", "http://www.ncbi.nlm.nih.gov/pubmed/25395816", "http://www.ncbi.nlm.nih.gov/pubmed/29796595" ], "ideal_answer": [ "Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine." ], "exact_answer": [ [ "dolutegravir" ], [ "abacavir" ], [ "lamivudine" ] ], "type": "list", "id": "5c7034ae7c78d69471000063", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "A patient with human immunodeficiency virus-1 infection presented with sub-acute liver failure, temporally related to commencement of an antiretroviral therapy regimen containing dolutegravir (Triumeq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059031", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 1142, "text": "Newer STRs include dolutegravir (DTG)/lamivudine (3TC)/abacavir (ABC) (Triumeq; Viiv Healthcare, Research Triangle Park, NC), rilpivirine (RPV)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (Odefsey; Gilead, Foster City, CA), RPV/FTC/tenofovir disoproxil fumarate (TDF) (Complera; Gilead), elvitegravir (EVG)/cobicistat (COBI)/FTC/TDF (Stribild; Gilead), and EVG/COBI/FTC/TAF (Genvoya; Gilead). Recently approved FDCs, such as atazanavir (ATV)/COBI (Evotaz; Bristol-Myers Squibb, Princeton, NJ), darunavir (DRV)/COBI (Prezcobix; Janssen Products, Titusville NJ), and FTC/TAF (Descovy; Gilead), are also now available. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29105160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Intentional overdose of dolutegravir/abacavir/lamivudine (Triumeq) in a 26-year-old man.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29533918", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine. Overdoses with Triumeq have not been reported previously. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29533918", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 479, "text": "Currently, there is no information about crushing of the branded fixed-dose combination of dolutegravir/abacavir/lamivudine (Triumeq\u00ae, referred to as TRI); therefore, crushing of TRI is not recommended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29796595", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 507, "text": "On running short of medication, he admitted to sharing his partner's treatment (Triumeq; abacavir, lamivudine and dolutegravir). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27530904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Abacavir/Dolutegravir/Lamivudine (Triumeq)-Induced Liver Toxicity in a Human Immunodeficiency Virus-Infected Patient.Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748198", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Abacavir/Dolutegravir/Lamivudine (Triumeq)-Induced Liver Toxicity in a Human Immunodeficiency Virus-Infected Patient.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748198", "endSection": "title" }, { "offsetInBeginSection": 378, "offsetInEndSection": 506, "text": "On running short of medication, he admitted to sharing his partner's treatment (Triumeq; abacavir, lamivudine and dolutegravir).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27530904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Naltrexone/bupropion (Contrave) for weight management; pembrolizumab (Keytruda) for melanoma; dolutegravir/abacavir/lamivudine (Triumeq) for HIV-1; and immune globulin infusion 10% (human) with recombinant human hyaluronidase (Hyqvia) for primary immunodeficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25395816", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 447, "text": "Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27912079", "endSection": "abstract" } ] }, { "body": "Are there graph kernel libraries available implemented in JAVA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29028902" ], "ideal_answer": [ "No. Measuring the similarity of graphs is a fundamental step in the analysis of graph-structured data, which is omnipresent in computational biology. Graph kernels have been proposed as a powerful and efficient approach to this problem of graph comparison. Graphkernels are the first R and Python graph kernel libraries including baseline kernels such as label histogram based kernels, classic graph kernels such as random walk based kernels, and the state-of-the-art Weisfeiler-Lehman graph kernel. The core of all graph kernels is implemented in C\u2009++ for efficiency. Using the kernel matrices computed by the package, one can perform tasks such as classification, regression and clustering on graph-structured samples." ], "exact_answer": "no", "type": "yesno", "id": "5c6d97497c78d69471000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "graphkernels: R and Python packages for graph comparison.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028902", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 744, "text": "Measuring the similarity of graphs is a fundamental step in the analysis of graph-structured data, which is omnipresent in computational biology. Graph kernels have been proposed as a powerful and efficient approach to this problem of graph comparison. Here we provide graphkernels, the first R and Python graph kernel libraries including baseline kernels such as label histogram based kernels, classic graph kernels such as random walk based kernels, and the state-of-the-art Weisfeiler-Lehman graph kernel. The core of all graph kernels is implemented in C\u2009++ for efficiency. Using the kernel matrices computed by the package, we can easily perform tasks such as classification, regression and clustering on graph-structured samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29028902", "endSection": "abstract" } ] }, { "body": "What organism causes hepatic capillariasis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28460612", "http://www.ncbi.nlm.nih.gov/pubmed/20135717", "http://www.ncbi.nlm.nih.gov/pubmed/25911041" ], "ideal_answer": [ "Hepatic capillariasis is a rare and neglected parasitic disease caused by infection with Capillaria hepatica in human liver.", "hepatic capillariasis, caused by the parasite Capillaria hepatica," ], "exact_answer": [ "Capillaria hepatica" ], "type": "factoid", "id": "5c571dd307647bbc4b000016", "snippets": [ { "offsetInBeginSection": 165, "offsetInEndSection": 231, "text": "hepatic capillariasis, caused by the parasite Capillaria hepatica,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28460612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Capillaria hepatica which accidentally infects humans is a zoonotic parasite of mammalian liver, primarily rodents and causes hepatic capillariasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25911041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Capillaria hepatica (C. hepatica) is a parasitic nematode causing hepatic capillariasis in numerous mammals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20135717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Capillaria hepatica which accidentally infects humans is a zoonotic parasite of mammalian liver, primarily rodents and causes hepatic capillariasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25911041", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 302, "text": "One of them is hepatic capillariasis, caused by the parasite Capillaria hepatica, primarily a disease of rodents, with hepatic manifestations in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28460612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Capillaria hepatica (C. hepatica) is a parasitic nematode causing hepatic capillariasis in numerous mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20135717", "endSection": "abstract" } ] }, { "body": "Cerliponase alfa is apprived for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "http://www.ncbi.nlm.nih.gov/pubmed/30205177", "http://www.ncbi.nlm.nih.gov/pubmed/28890641", "http://www.ncbi.nlm.nih.gov/pubmed/29688815" ], "ideal_answer": [ "Cerliponase alfa is a recombinant human tripeptidyl peptidase-1 (TPP1) approved for use in patients with neuronal ceroid lipofuscinosis type 2 (CLN2), a paediatric neurodegenerative disease caused by a deficiency in TPP1." ], "exact_answer": [ "neuronal ceroid lipofuscinosis type 2" ], "type": "factoid", "id": "5c6b810e7c78d6947100002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Study of Intraventricular Cerliponase Alfa for CLN2 Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "BACKGROUND: Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 1927, "offsetInEndSection": 2106, "text": "CONCLUSIONS: Intraventricular infusion of cerliponase alfa in patients with CLN2 disease resulted in less decline in motor and language function than that in historical controls. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Immunogenicity to cerliponase alfa intracerebroventricular enzyme replacement therapy for CLN2 disease: Results from a Phase 1/2 study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30205177", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Treatment with intracerebroventricular (ICV)-delivered cerliponase alfa enzyme replacement therapy (ERT) in a Phase 1/2 study of 24 subjects with CLN2 disease resulted in a meaningful preservation of motor and language (ML) function and was well tolerated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30205177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 801, "text": "Cerliponase alfa (Brineura\u2122) is a recombinant human tripeptidyl peptidase-1 (TPP1) being developed by BioMarin Pharmaceutical Inc. for use in patients with neuronal ceroid lipofuscinosis type 2 (CLN2), a paediatric neurodegenerative disease caused by a deficiency in TPP1. CLN2 is characterised by progressive impairment of motor function, language deficiencies, seizures, ataxia, blindness and early death, and intracerebroventricular infusion of cerliponase alfa has been shown to reduce the progression of functional decline. This article summarizes the milestones in the development of cerliponase alfa leading to its first global approval in the USA for the treatment of motor function loss in paediatric patients \u22653\u00a0years of age with CLN2, and subsequent approval in the EU for CLN2 in all ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 841, "text": "This article summarizes the milestones in the development of cerliponase alfa leading to its first global approval in the USA for the treatment of motor function loss in paediatric patients \u22653\u00a0years of age with CLN2, and subsequent approval in the EU for CLN2 in all ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Cerliponase Alfa: First Global Approval.Cerliponase alfa (Brineura\u2122) is a recombinant human tripeptidyl peptidase-1 (TPP1) being developed by BioMarin Pharmaceutical Inc. for use in patients with neuronal ceroid lipofuscinosis type 2 (CLN2), a paediatric neurodegenerative disease caused by a deficiency in TPP1. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Pharmaceutical Approval Update.Sarilumab (Kevzara) for moderately to severely active rheumatoid arthritis; valbenazine (Ingrezza), the first approval for tardive dyskinesia; and cerliponase alpha (Brineura) for late infantile neuronal ceroid lipofuscinosis type-2 disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28890641", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Study of Intraventricular Cerliponase Alfa for CLN2 Disease.Intraventricular infusion of cerliponase alfa in patients with CLN2 disease resulted in less decline in motor and language function than that in historical controls. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "title" }, { "offsetInBeginSection": 313, "offsetInEndSection": 568, "text": "CLN2 is characterised by progressive impairment of motor function, language deficiencies, seizures, ataxia, blindness and early death, and intracerebroventricular infusion of cerliponase alfa has been shown to reduce the progression of functional decline. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Cerliponase alfa (Brineura\u2122) is a recombinant human tripeptidyl peptidase-1 (TPP1) being developed by BioMarin Pharmaceutical Inc. for use in patients with neuronal ceroid lipofuscinosis type 2 (CLN2), a paediatric neurodegenerative disease caused by a deficiency in TPP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 528, "text": "CLN2 is characterised by progressive impairment of motor function, language deficiencies, seizures, ataxia, blindness and early death, and intracerebroventricular infusion of cerliponase alfa has been shown to reduce the progression of functional decline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 801, "text": "This article summarizes the milestones in the development of cerliponase alfa leading to its first global approval in the USA for the treatment of motor function loss in paediatric patients \u22653\u00a0years of age with CLN2, and subsequent approval in the EU for CLN2 in all ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Treatment with intracerebroventricular (ICV)-delivered cerliponase alfa enzyme replacement therapy (ERT) in a Phase 1/2 study of 24 subjects with CLN2 disease resulted in a meaningful preservation of motor and language (ML) function and was well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30205177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "BACKGROUND\nRecombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 1933, "offsetInEndSection": 2110, "text": "CONCLUSIONS\nIntraventricular infusion of cerliponase alfa in patients with CLN2 disease resulted in less decline in motor and language function than that in historical controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "BACKGROUND Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 1933, "offsetInEndSection": 2110, "text": "CONCLUSIONS Intraventricular infusion of cerliponase alfa in patients with CLN2 disease resulted in less decline in motor and language function than that in historical controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 805, "text": "This article summarizes the milestones in the development of cerliponase alfa leading to its first global approval in the USA for the treatment of motor function loss in paediatric patients \u22653\u00a0years of age with CLN2, and subsequent approval in the EU for CLN2 in all ages.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28589525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 488, "text": "BACKGROUND: Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.
METHODS: In a multicenter, open-label study, we evaluated the effect of intraventricular infusion of cerliponase alfa every 2 weeks in children with CLN2 disease who were between the ages of 3 and 16 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 1788, "offsetInEndSection": 2145, "text": "In 2 patients, infections developed in the intraventricular device that was used to administer the infusion, which required antibiotic treatment and device replacement.
CONCLUSIONS: Intraventricular infusion of cerliponase alfa in patients with CLN2 disease resulted in less decline in motor and language function than that in historical controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Sarilumab (Kevzara) for moderately to severely active rheumatoid arthritis; valbenazine (Ingrezza), the first approval for tardive dyskinesia; and cerliponase alpha (Brineura) for late infantile neuronal ceroid lipofuscinosis type-2 disease.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28890641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Sarilumab (Kevzara) for moderately to severely active rheumatoid arthritis; valbenazine (Ingrezza), the first approval for tardive dyskinesia; and cerliponase alpha (Brineura) for late infantile neuronal ceroid lipofuscinosis type-2 disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28890641", "endSection": "abstract" }, { "offsetInBeginSection": 1903, "offsetInEndSection": 2068, "text": "Intraventricular infusion of cerliponase alfa in patients with CLN2 disease resulted in less decline in motor and language function than that in historical controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688815", "endSection": "abstract" } ] }, { "body": "Is baricitinib effective for rheumatoid arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28097393", "http://www.ncbi.nlm.nih.gov/pubmed/28440680", "http://www.ncbi.nlm.nih.gov/pubmed/24818516", "http://www.ncbi.nlm.nih.gov/pubmed/29134891", "http://www.ncbi.nlm.nih.gov/pubmed/27427830", "http://www.ncbi.nlm.nih.gov/pubmed/30058112", "http://www.ncbi.nlm.nih.gov/pubmed/29687421", "http://www.ncbi.nlm.nih.gov/pubmed/29500799", "http://www.ncbi.nlm.nih.gov/pubmed/30191390", "http://www.ncbi.nlm.nih.gov/pubmed/28199814", "http://www.ncbi.nlm.nih.gov/pubmed/28290136", "http://www.ncbi.nlm.nih.gov/pubmed/30219772", "http://www.ncbi.nlm.nih.gov/pubmed/28811354", "http://www.ncbi.nlm.nih.gov/pubmed/30006916", "http://www.ncbi.nlm.nih.gov/pubmed/29415145", "http://www.ncbi.nlm.nih.gov/pubmed/30183607" ], "ideal_answer": [ "Yes, baricitinib is effective treatment of rheumatoid arthritis." ], "exact_answer": "yes", "type": "yesno", "id": "5c6df86b7c78d69471000045", "snippets": [ { "offsetInBeginSection": 1551, "offsetInEndSection": 1735, "text": "CONCLUSION: Baricitinib 2\u2009mg and 4\u2009mg administered once daily, in combination with DMARD, were efficacious interventions for active RA that had no significant risk of TEAE development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28097393", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1342, "text": "CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28440680", "endSection": "abstract" }, { "offsetInBeginSection": 1285, "offsetInEndSection": 1562, "text": "CONCLUSION: In a phase IIb study in RA, the safety and tolerability profile of baricitinib, up to 128 weeks, remained consistent with earlier observations, without unexpected late signals. Clinical improvements seen in the 24-week blinded period were maintained during the OLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28811354", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1472, "text": "CONCLUSION: Data for baricitinib, with/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy/safety profile in overall study populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29134891", "endSection": "abstract" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1750, "text": "Conclusion: Baricitinib demonstrated a consistent, beneficial treatment effect in bDMARD-refractory patients across subgroups based on baseline characteristics and prior bDMARD use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29415145", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 332, "text": "Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6\u00a0months of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "OBJECTIVE\nBaricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30058112", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1175, "text": "EXPERT OPINION\nJAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24818516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "OBJECTIVE\nBaricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30219772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29500799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Baricitinib for the treatment of rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27427830", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "OBJECTIVES\nOral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30183607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Baricitinib (Olumiant\u2122) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28290136", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1175, "text": "EXPERT OPINION JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24818516", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 927, "text": "Tofacitinib 10\u202fmg\u202f+\u2009methotrexate (MTX) and baricitinib 4\u202fmg\u202f+\u2009MTX were among the most effective treatments for active RA with an inadequate DMARD or biologic response, followed by baricitinib 2\u202fmg\u202f+\u2009MTX, tofacitinib 5\u202fmg\u202f+\u2009MTX, and adalimumab\u202f+\u2009MTX.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "OBJECTIVE Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30058112", "endSection": "abstract" }, { "offsetInBeginSection": 2026, "offsetInEndSection": 2234, "text": "CONCLUSIONS In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28199814", "endSection": "abstract" }, { "offsetInBeginSection": 1273, "offsetInEndSection": 1587, "text": "Thus, once-daily baricitinib, as monotherapy or in combination with methotrexate, is an effective and generally well tolerated emerging treatment for patients with moderate to severe active RA who have responded inadequately to or are intolerant of \u2265\u00a01 DMARD, and extends the options available for this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29687421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "OBJECTIVES Oral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30183607", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 823, "text": "Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and na\u00efve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27427830", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1168, "text": "It is also reported that safety was tolerable within the limited study period.
AREAS COVERED: We here review the recent progress in the development of baricitinib and its potential for the treatment of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27427830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "OBJECTIVE: Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30058112", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 802, "text": "In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28290136", "endSection": "abstract" }, { "offsetInBeginSection": 1999, "offsetInEndSection": 2195, "text": "In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28199814", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 838, "text": "In pivotal multinational trials, once-daily baricitinib 4\u00a0mg, with/without methotrexate (\u00b1\u00a0another csDMARD), improved the signs and symptoms of RA, disease activity and physical function in DMARD-naive patients and in patients with an inadequate response to methotrexate, csDMARDs or TNF inhibitors; baricitinib treatment also slowed structural joint damage in DMARD-naive patients and in those with an inadequate response to methotrexate and csDMARDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29687421", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 802, "text": "Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and na\u00efve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27427830", "endSection": "abstract" } ] }, { "body": "What is the function of PARP1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26184161", "http://www.ncbi.nlm.nih.gov/pubmed/21543585", "http://www.ncbi.nlm.nih.gov/pubmed/29851986", "http://www.ncbi.nlm.nih.gov/pubmed/28930534", "http://www.ncbi.nlm.nih.gov/pubmed/19622798", "http://www.ncbi.nlm.nih.gov/pubmed/24782312", "http://www.ncbi.nlm.nih.gov/pubmed/22053002", "http://www.ncbi.nlm.nih.gov/pubmed/27440880", "http://www.ncbi.nlm.nih.gov/pubmed/28698968" ], "ideal_answer": [ "parp1 is the most abundant and best-characterized member of the family of parp enzymes. the poly(adp-ribose) polymerases (parps) catalyze poly(adp-ribosyl)ation, a post-translational modification of proteins.", "parp1 plays key roles in dna repair, as well as a wide variety of cellular processes, including transcriptional regulation", "PARP1 is an abundant nuclear protein with many pleiotropic functions involved in epigenetic and transcriptional controls. PARP1 plays key roles in DNA repair, as well as a wide variety of cellular processes, including transcriptional regulation, chromatin modulation, cellular signaling pathway, inflammation, cellular stress responses and so on.", "PARP1 plays key roles in DNA repair, as well as a wide variety of cellular processes, including transcriptional regulation, chromatin modulation, cellular signaling pathway, inflammation, cellular stress responses and so on" ], "type": "summary", "id": "5c8436f875a4a5d219000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 618, "text": "The poly(ADP-ribose) polymerases (PARPs) catalyze poly(ADP-ribosyl)ation, a post-translational modification of proteins. This\u00a0 consists of the attachment of mono- or poly-adenosine diphosphate (ADP)-ribose units from nicotinamide adenine dinucleotide (NAD+) to specific polar residues of target proteins. PARP1 is the most abundant and best-characterized member of the family of PARP enzymes. PARP1 plays key roles in DNA repair, as well as a wide variety of cellular processes, including transcriptional regulation, chromatin modulation, cellular signaling pathway, inflammation, cellular stress responses and so on. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28930534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Poly(ADP-ribose)polymerase-1 (PARP1) controls adipogenic gene expression and adipocyte function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22053002", "endSection": "title" }, { "offsetInBeginSection": 275, "offsetInEndSection": 399, "text": "PARP1 functions as a transcriptional coactivator of nuclear factor kappaB (NF-kappaB) and hypoxia inducible factor 1 (HIF1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Poly(ADP-ribose)polymerase-1 (PARP1) is a chromatin-associated enzyme that was described to affect chromatin compaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22053002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Poly(ADP-ribose) polymerase 1 (PARP1, also known as ARTD1) is an abundant nuclear enzyme that plays important roles in DNA repair, gene transcription, and differentiation through the modulation of chromatin structure and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24782312", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 152, "text": "Poly(ADP-ribose) polymerase 1 (PARP1) is known for its function in nuclear DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29851986", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 948, "text": "PARP1 regulates gene expression by numerous mechanisms, including modifying chromatin structure and altering the function of chromatin-modifying enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440880", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 317, "text": "Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear zinc-finger protein with a function as a DNA damage sensor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21543585", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 405, "text": "Being a major member of Parps, Parp1 is a crucial nuclear factor with biological significance in modulating DNA repair, DNA replication, transcription, DNA methylation and chromatin remodeling through PARylation of downstream proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26184161", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 565, "text": "We thus hypothesized that PARP1 plays an important transcriptional role in adipogenesis and metabolism and therefore used adipocyte development and function as a model to elucidate the molecular action of PARP1 in obesity-related diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22053002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Poly(ADP-ribose)polymerase-1 (PARP1) controls adipogenic gene expression and adipocyte function.Poly(ADP-ribose)polymerase-1 (PARP1) is a chromatin-associated enzyme that was described to affect chromatin compaction. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22053002", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Poly(ADP-ribose) polymerase 1 (PARP1) is a chromatin-associated nuclear protein and functions as a molecular stress sensor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19622798", "endSection": "abstract" } ] }, { "body": "Is Semagacestat effective for treatment of Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "http://www.ncbi.nlm.nih.gov/pubmed/23785331", "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "http://www.ncbi.nlm.nih.gov/pubmed/23196551", "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "http://www.ncbi.nlm.nih.gov/pubmed/25292430", "http://www.ncbi.nlm.nih.gov/pubmed/21149978", "http://www.ncbi.nlm.nih.gov/pubmed/28978478" ], "ideal_answer": [ "No. In clinical trial semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. Semagacestat was associated with more adverse events, including skin cancers and infections." ], "exact_answer": "no", "type": "yesno", "id": "5c73acf27c78d6947100008a", "snippets": [ { "offsetInBeginSection": 173, "offsetInEndSection": 402, "text": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28978478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 398, "text": "A clinical trial with the wide-spectrum \u03b3-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all \u03b3-secretases causes serious toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25292430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "OBJECTIVE: Semagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "endSection": "abstract" }, { "offsetInBeginSection": 2360, "offsetInEndSection": 2626, "text": "CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. Semagacestat was associated with more adverse events, including skin cancers and infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "BACKGROUND\nIn a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "endSection": "abstract" }, { "offsetInBeginSection": 2539, "offsetInEndSection": 2631, "text": "Semagacestat was associated with more adverse events, including skin cancers and infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 2366, "offsetInEndSection": 2538, "text": "CONCLUSIONS\nAs compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "OBJECTIVE\nSemagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 640, "text": "Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23785331", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The recent failure of semagacestat in two large Phase III studies questions the value of \u03b3-secretase inhibitors in treating Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "A phase 3 trial of semagacestat for treatment of Alzheimer's disease.As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "title" }, { "offsetInBeginSection": 754, "offsetInEndSection": 983, "text": "Preliminary results from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Changes in Neuropsychiatric Inventory Associated with Semagacestat Treatment of\u00a0Alzheimer's Disease.In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "endSection": "title" }, { "offsetInBeginSection": 1950, "offsetInEndSection": 2164, "text": "Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "OBJECTIVE: Semagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1099, "text": "Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "endSection": "abstract" }, { "offsetInBeginSection": 1896, "offsetInEndSection": 2113, "text": "Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Semagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "endSection": "abstract" } ] }, { "body": "Which molecule is inhibited by ivosidenib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29266015", "http://www.ncbi.nlm.nih.gov/pubmed/29950729", "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "http://www.ncbi.nlm.nih.gov/pubmed/30209701", "http://www.ncbi.nlm.nih.gov/pubmed/30093505", "http://www.ncbi.nlm.nih.gov/pubmed/29934313" ], "ideal_answer": [ "Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1. It used an effective treatment of leukemia." ], "exact_answer": [ "IDH1" ], "type": "factoid", "id": "5c73ace87c78d69471000084", "snippets": [ { "offsetInBeginSection": 815, "offsetInEndSection": 1188, "text": "Different combinations and new formulations of cytotoxic agents, such as clofarabine or CPX-351, are newer options for specific subsets of patients. Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29266015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "endSection": "title" }, { "offsetInBeginSection": 460, "offsetInEndSection": 688, "text": "Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 225, "text": " Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "A phase I study suggests that ivosidenib can induce remission in patients with relapsed or refractory acute myeloid leukemia characterized by IDH1 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29934313", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1563, "text": "Biochemical studies predicted that resistance to allosteric IDH inhibitors could also occur via IDH dimer-interface mutations in cis, which was confirmed in a patient with acquired resistance to the IDH1 inhibitor ivosidenib (AG-120).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29950729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30093505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Ivosidenib (Tibsovo\u00ae) is a small molecule, orally available inhibitor of mutated cytosolic isocitrate dehydrogenase 1 (IDH1) that is being developed by Agios Pharmaceuticals for the treatment of cancer in patients with IDH1 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30209701", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 872, "text": "This article summarizes the milestones in the development of ivosidenib leading to this first approval in the USA for the treatment of patients with relapsed or refractory AML with a susceptible IDH1 mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30209701", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 662, "text": "Ivosidenib targets the IDH1 metabolic pathway to prevent a build-up of the oncometabolite 2-HG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30209701", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 224, "text": "Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "title" }, { "offsetInBeginSection": 227, "offsetInEndSection": 345, "text": "METHODS\nWe conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 2003, "offsetInEndSection": 2330, "text": "CONCLUSIONS\nIn patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 687, "text": "Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1189, "text": "Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29266015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30093505", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1157, "text": "Biochemical studies predicted that resistance to allosteric IDH inhibitors could also occur via IDH dimer-interface mutations in cis, which was confirmed in a patient with acquired resistance to the IDH1 inhibitor ivosidenib (AG-120). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29950729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670690", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 393, "text": "Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML.In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "title" }, { "offsetInBeginSection": 150, "offsetInEndSection": 362, "text": "Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.
METHODS: We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 213, "text": "Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 324, "text": "We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" }, { "offsetInBeginSection": 1968, "offsetInEndSection": 2283, "text": "In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29860938", "endSection": "abstract" } ] }, { "body": "What is COG112?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16740622" ], "ideal_answer": [ "COG112 is a a modified apoE-mimetic peptide, that results from the fusion of COG133 to a protein transduction domain. COG112 has significantly enhanced anti-inflammatory bioactivities in vitro." ], "type": "summary", "id": "5c88593d75a4a5d21900000a", "snippets": [ { "offsetInBeginSection": 728, "offsetInEndSection": 1018, "text": "Most notably, fusion of COG133 to a protein transduction domain creates COG112, a modified apoE-mimetic peptide with significantly enhanced anti-inflammatory bioactivities in vitro, and improved therapeutic effects on EAE in vivo, which renders a nearly full remission from the disability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16740622", "endSection": "abstract" } ] }, { "body": "List the four advances integrated into the SHERLOCKv2 platform.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29449508" ], "ideal_answer": [ "SHERLOCKv2 presents with four distinct advances: (i) four-channel single-reaction multiplexing with orthogonal CRISPR enzymes; (ii) quantitative measurement of input as low as 2 attomolar; (iii) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme; and (iv) lateral-flow readout." ], "exact_answer": [ [ "four-channel single-reaction multiplexing with orthogonal CRISPR enzymes" ], [ "quantitative measurement of input as low as 2 attomolar" ], [ "3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme" ], [ "lateral-flow readout" ] ], "type": "list", "id": "5c928958ecadf2e73f000017", "snippets": [ { "offsetInBeginSection": 306, "offsetInEndSection": 744, "text": "Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCK version 2 (SHERLOCKv2) (i) four-channel single-reaction multiplexing with orthogonal CRISPR enzymes; (ii) quantitative measurement of input as low as 2 attomolar; (iii) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme; and (iv) lateral-flow readout. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29449508", "endSection": "abstract" } ] }, { "body": "Does Rhamnose have any effect on aging?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28855134", "http://www.ncbi.nlm.nih.gov/pubmed/22099844" ], "ideal_answer": [ "Yes, Rhamnose does have an effect on aging." ], "exact_answer": "yes", "type": "yesno", "id": "5c840daf617e120c34000007", "snippets": [ { "offsetInBeginSection": 740, "offsetInEndSection": 892, "text": "The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28855134", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 830, "text": "Some of these mechanisms will be reviewed as well as the capacity of fucose- and rhamnose-rich oligo- and polysaccharides (FROP and RROP) to counteract several of the mechanisms involved in skin aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22099844", "endSection": "abstract" } ] }, { "body": "Is there any approved treatment for NAFLD?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30016770", "http://www.ncbi.nlm.nih.gov/pubmed/29247356", "http://www.ncbi.nlm.nih.gov/pubmed/29122694", "http://www.ncbi.nlm.nih.gov/pubmed/29448843" ], "ideal_answer": [ "No,\nNonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy." ], "exact_answer": "no", "type": "yesno", "id": "5c7d6b3e45e140a523000001", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 164, "text": "Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30016770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 397, "text": "Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortality. However, there are currently no approved pharmacologic therapies for NASH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29122694", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1123, "text": "Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29122694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29247356", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 158, "text": "Nonalcoholic fatty liver disease (NAFLD) has an increasing prevalence worldwide. At present, no specific pharmacotherapy is approved for NAFLD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29448843", "endSection": "abstract" } ] }, { "body": "Can pazopanib be used for treatment von Hippel-Lindau disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26497655", "http://www.ncbi.nlm.nih.gov/pubmed/29396065", "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "http://www.ncbi.nlm.nih.gov/pubmed/22374327" ], "ideal_answer": [ "Yes, pazopanib is used for treatment von Hippel-Lindau disease." ], "exact_answer": "yes", "type": "yesno", "id": "5c72bd047c78d69471000077", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Variable response of CNS hemangioblastomas to Pazopanib in a single patient with von Hippel-Lindau disease: Case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29396065", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 612, "text": "Treatment of RCCs with tyrosine kinase inhibitors (TKIs) such as Pazopanib is now first line therapy, but their effect on VHL-associated CNS HBs remains unknown. We report the use of Pazopanib in a patient with VHL disease for treatment of RCC who also harbored multiple CNS HBs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29396065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "title" }, { "offsetInBeginSection": 2195, "offsetInEndSection": 2559, "text": "INTERPRETATION: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26497655", "endSection": "title" }, { "offsetInBeginSection": 499, "offsetInEndSection": 760, "text": " Here, we report a 37-year-old woman's case with recurrent and rapidly progressive VHL-associated hemangioblastomas, causing severe disability. She was treated 24 months with pazopanib, a multityrosine kinase inhibitor (TKI) targeting VEGF and PDGF-\u03b2 pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26497655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374327", "endSection": "title" }, { "offsetInBeginSection": 723, "offsetInEndSection": 968, "text": "Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374327", "endSection": "abstract" }, { "offsetInBeginSection": 2382, "offsetInEndSection": 2563, "text": "Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 828, "text": "METHODS\nIn this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 435, "text": "We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 2201, "offsetInEndSection": 2381, "text": "INTERPRETATION\nPazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1523, "text": "FINDINGS\nBetween Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report.von Hippel-Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22374327", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26497655", "endSection": "title" }, { "offsetInBeginSection": 344, "offsetInEndSection": 845, "text": "We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease.
METHODS: In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1549, "text": "This study is registered with ClinicalTrials.gov, number NCT01436227, and is closed to accrual.
FINDINGS: Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 2092, "offsetInEndSection": 2416, "text": "Treatment-related serious adverse events included one case each of appendicitis and gastritis and one patient had a fatal CNS bleed.
INTERPRETATION: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 2417, "offsetInEndSection": 2598, "text": "Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 424, "text": "We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 807, "text": "In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 2167, "offsetInEndSection": 2332, "text": "Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 2333, "offsetInEndSection": 2514, "text": "Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1491, "text": "Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30236511", "endSection": "abstract" } ] }, { "body": "Which ploidy-agnostic method has been developed for estimating telomere length from whole genome sequencing data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29358629" ], "ideal_answer": [ "Telomerecat is a ploidy-agnostic method for estimating telomere length from whole genome sequencing data. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors." ], "exact_answer": [ "Telomerecat" ], "type": "factoid", "id": "5c61f767e842deac67000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358629", "endSection": "title" }, { "offsetInBeginSection": 312, "offsetInEndSection": 1370, "text": "To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358629", "endSection": "title" } ] }, { "body": "What happens to retrotransposons during ageing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27692431", "http://www.ncbi.nlm.nih.gov/pubmed/26581630" ], "ideal_answer": [ "Retrotransposons are activated as organisms age" ], "exact_answer": [ "Activation" ], "type": "factoid", "id": "5c929094ecadf2e73f000019", "snippets": [ { "offsetInBeginSection": 249, "offsetInEndSection": 570, "text": "Senescent cells undergo dramatic alterations to their chromatin landscape that affect genome accessibility and their transcriptional program. These include the loss of DNA-nuclear lamina interactions, the distension of centromeres, and changes in chromatin composition that can lead to the activation of retrotransposons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27692431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Retrotransposons are activated as organisms age, based on work from several model systems. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26581630", "endSection": "abstract" } ] }, { "body": "What is the function of Taraxasterol in rheumatoid arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28101182", "http://www.ncbi.nlm.nih.gov/pubmed/27109342" ], "ideal_answer": [ "Taraxasterol suppresses inflammation in rheumatoid arthritis.", "Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses" ], "type": "summary", "id": "5c85171875a4a5d219000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28101182", "endSection": "title" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1290, "text": "These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28101182", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1291, "text": "These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28101182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28101182", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice.. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28101182", "endSection": "title" } ] }, { "body": "Is Netrin-1 a secreted protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21303223", "http://www.ncbi.nlm.nih.gov/pubmed/17174565", "http://www.ncbi.nlm.nih.gov/pubmed/26039999", "http://www.ncbi.nlm.nih.gov/pubmed/28174720", "http://www.ncbi.nlm.nih.gov/pubmed/22046354", "http://www.ncbi.nlm.nih.gov/pubmed/24174661" ], "ideal_answer": [ "Yes,\nnetrin-1 is a secreted protein." ], "exact_answer": "yes", "type": "yesno", "id": "5c89461675a4a5d219000013", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 109, "text": "The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21303223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain during the postnatal period of peak synapse formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24174661", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 384, "text": " Netrin-1, a laminin-related secreted protein, displays proto-oncogenic activity in cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26039999", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 108, "text": "Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28174720", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 135, "text": "etrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22046354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Netrins are a family of secreted protein related to laminin and act as tropic cues directing axon growth and cell migration during neural development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17174565", "endSection": "abstract" } ] }, { "body": "Which enzyme is deficient in Wolman disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29246491", "http://www.ncbi.nlm.nih.gov/pubmed/11019848", "http://www.ncbi.nlm.nih.gov/pubmed/24798600", "http://www.ncbi.nlm.nih.gov/pubmed/8397511", "http://www.ncbi.nlm.nih.gov/pubmed/179993", "http://www.ncbi.nlm.nih.gov/pubmed/9925650", "http://www.ncbi.nlm.nih.gov/pubmed/28659158", "http://www.ncbi.nlm.nih.gov/pubmed/28374935", "http://www.ncbi.nlm.nih.gov/pubmed/29374495", "http://www.ncbi.nlm.nih.gov/pubmed/8864960", "http://www.ncbi.nlm.nih.gov/pubmed/29547398", "http://www.ncbi.nlm.nih.gov/pubmed/29339442", "http://www.ncbi.nlm.nih.gov/pubmed/8576647" ], "ideal_answer": [ "Deficiency of lysosomal acid lipase (LAL) causes Wolman disease." ], "exact_answer": [ "lysosomal acid lipase" ], "type": "factoid", "id": "5c72f6b17c78d6947100007f", "snippets": [ { "offsetInBeginSection": 260, "offsetInEndSection": 646, "text": "Wolman's disease, also known as lysosomal acid lipase (LIPA) deficiency, is a rare autosomal-recessive disorder characterized by complete absence of the LIPA enzyme. The diagnosis of Wolman's disease was made postnatally by biochemical testing, which indicated absence of LIPA enzyme activity and gene sequencing, which confirmed homozygosity for the G66V mutation within the LIPA gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28374935", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 331, "text": "These include Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD) which both result from mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29246491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "BACKGROUND: Deficiency of lysosomal acid lipase (LAL) causes Wolman disease and cholesterol ester storage disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29339442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND: Lysosomal acid lipase deficiency is an autosomal recessive metabolic disease with a wide range of severity from Wolman Disease to Cholesterol Ester Storage Disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374495", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 755, "text": " In humans, loss-of-function mutations of LIPA cause rare lysosomal disorders, Wolman disease, and cholesteryl ester storage disease, in which LAL enzyme replacement therapy has shown significant benefits in a phase 3 clinical trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Cholesteryl ester storage disease (CESD, OMIM #278000) and Wolman disease (OMIM #278000) are autosomal recessive lysosomal storage disorders caused by a deficient activity of lysosomal acid lipase (cholesteryl ester hydrolase, LAL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798600", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 518, "text": "Wolman disease, associated with deficient hLAL activity, leads to massive intracellular substrate accumulation and is always fatal in early infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925650", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 231, "text": "We previously reported a rat model of Wolman's disease (Wolman rat) that is deficient for LAL activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8576647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND\nWolman disease (WD) is a rare lysosomal storage disorder that is caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28659158", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 537, "text": "We report successful long-term bone marrow engraftment in a patient with Wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11019848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "A new mutation in the gene for lysosomal acid lipase leads to Wolman disease in an African kindred.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8864960", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity and genetic defects of lysosomal acid lipase (LAL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8864960", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 442, "text": "In Wolman disease, LAL activity is usually absent, whereas CESD usually presents some residual LAL activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798600", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 652, "text": "Wolman disease, associated with deficient hLAL activity, leads to massive intracellular substrate accumulation and is always fatal in early infancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925650", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 531, "text": "Acta 1006, 84-88], has been administered to cultured lymphoblastoid cells from normal subjects and from a patient affected with Wolman disease, which is characterized by a deficiency of lysosomal acid lipase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8397511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "A new mutation in the gene for lysosomal acid lipase leads to Wolman disease in an African kindred.Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity and genetic defects of lysosomal acid lipase (LAL). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8864960", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Lysosomal acid lipase deficiency: wolman disease and cholesteryl ester storage disease.Cholesteryl ester storage disease (CESD, OMIM #278000) and Wolman disease (OMIM #278000) are autosomal recessive lysosomal storage disorders caused by a deficient activity of lysosomal acid lipase (cholesteryl ester hydrolase, LAL). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798600", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Restoration of a regulatory response to low density lipoprotein in acid lipase-deficient human fibroblasts.Previous studies have shown that cultured fibroblasts derived from patients with genetic defects in lysosomal acid lipase (i. e. the Wolman Syndrome and Cholesteryl Ester Storage Disease) are defective in their ability to hydrolyze the cholesteryl esters contained in plasma low density lipoprotein (LDL). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/179993", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "Molecular defects underlying Wolman disease appear to be more heterogeneous than those resulting in cholesteryl ester storage disease.Human lysosomal acid lipase/cholesteryl ester hydrolase (hLAL) is essential for the intralysosomal metabolism of cholesteryl esters and triglycerides taken up by receptor-mediated endocytosis of lipoprotein particles. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925650", "endSection": "title" }, { "offsetInBeginSection": 700, "offsetInEndSection": 903, "text": "In order to elucidate the underlying molecular defects in Wolman disease, we have characterized the hLAL gene in two female Wolman patients of German and Turkish origin by SSCP and DNA sequence analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9925650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Lysosomal acid lipase deficiency: wolman disease and cholesteryl ester storage disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798600", "endSection": "title" } ] }, { "body": "Is the yeast (Saccharomyces cerevisiae) genome organized into topologically associated domains (TADs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28348222", "http://www.ncbi.nlm.nih.gov/pubmed/28780612" ], "ideal_answer": [ "Yes. By analyzing Hi-C data for budding yeast, 200-kb scale topologically associated domains (TADs) have been identified, whose boundaries are enriched for transcriptional activity." ], "exact_answer": "yes", "type": "yesno", "id": "5c62a529e842deac6700000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 739, "text": "Recent advances in our understanding of the three-dimensional organization of the eukaryotic nucleus have rendered the spatial distribution of genes increasingly relevant. In a recent work (Tsochatzidou et al., Nucleic Acids Res 45:5818-5828, 2017), we proposed the existence of a functional compartmentalization of the yeast genome according to which, genes occupying the chromosomal regions at the nuclear periphery have distinct structural, functional and evolutionary characteristics compared to their centromeric-proximal counterparts. Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28780612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Form and function of topologically associating genomic domains in budding yeast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28348222", "endSection": "title" }, { "offsetInBeginSection": 178, "offsetInEndSection": 1427, "text": "Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity. Furthermore, these boundaries separate regions of similarly timed replication origins connecting the long-known effect of genomic context on replication timing to genome architecture. To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing. Forkhead factors do not regulate TAD formation, but do promote longer-range genomic interactions and control interactions between origins near the centromere. Thus, our work defines spatial organization within the budding yeast nucleus, demonstrates the conserved role of genome architecture in regulating DNA replication, and identifies a molecular mechanism specifically regulating interactions between pericentric origins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28348222", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 739, "text": "Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28780612", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 847, "text": "Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28780612", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 614, "text": "In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28348222", "endSection": "abstract" } ] }, { "body": "What is MOV10?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29266590" ], "ideal_answer": [ "MOV10 is an RNA helicase" ], "exact_answer": [ "RNA helicase" ], "type": "factoid", "id": "5c93e5acecadf2e73f00001a", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 116, "text": "Mov10 is an RNA helicase that modulates access of Argonaute 2 to microRNA recognition elements in mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29266590", "endSection": "abstract" } ] }, { "body": "As of Feb 2019, are major brain gangliosides a target for the treatment of Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21274438", "http://www.ncbi.nlm.nih.gov/pubmed/7997071" ], "ideal_answer": [ "As of Feb 2019, major brain gangliosides are proposed as a target for the treatment of Alzheimer's disease." ], "exact_answer": "yes", "type": "yesno", "id": "5c72a5ca7c78d6947100006d", "snippets": [ { "offsetInBeginSection": 1061, "offsetInEndSection": 1222, "text": "An understanding of the mechanism on the interaction of GM1 and A\u03b2s in AD may contribute to the development of new neuroregenerative therapies for this disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21274438", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 517, "text": "Abnormal ganglioside metabolism also may occur in AD brains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21274438", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1192, "text": "Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7997071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7997071", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease.Gangliosides are glycosphingolipids localized to the outer leaflet of the plasma membrane of vertebrate cells. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7997071", "endSection": "title" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1196, "text": "Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I).
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7997071", "endSection": "abstract" } ] }, { "body": "Which cancer is associated with increased levels of Serum alpha fetoprotein (AFP) ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28989060", "http://www.ncbi.nlm.nih.gov/pubmed/28750141", "http://www.ncbi.nlm.nih.gov/pubmed/29052791", "http://www.ncbi.nlm.nih.gov/pubmed/28582340", "http://www.ncbi.nlm.nih.gov/pubmed/28482112" ], "ideal_answer": [ "Serum alpha fetoprotein (AFP) is a marker of germ cell neoplasms,\r\nSerum \u03b1-Fetoprotein (AFP) is a widely used diagnostic biomarker, but it has limited sensitivity and is not elevated in all HCC cases." ], "exact_answer": [ "HCC", "hepatocelluar carcinoma" ], "type": "factoid", "id": "5c89623bf9c2ba6b28000005", "snippets": [ { "offsetInBeginSection": 1624, "offsetInEndSection": 1864, "text": "In the competing-risk regression, the sum of tumor number and size and of log10 level of AFP were significantly associated with HCC-specific death (P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763-0.798).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28989060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Ovarian Sertoli-Leydig cell tumors (SLCTs) are uncommon neoplasms that are occasionally associated with an elevated level of serum alpha fetoprotein (AFP), a marker of germ cell neoplasms, particularly yolk sac tumor (YST). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28582340", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 610, "text": "Serum \u03b1-Fetoprotein (AFP) is a widely used diagnostic biomarker, but it has limited sensitivity and is not elevated in all HCC cases so, we incorporate a second blood-based biomarker, des'\u03b3 carboxy-prothrombin (DCP), that has shown potential as a screening marker for HCC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28482112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC), and surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is recommended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28750141", "endSection": "abstract" }, { "offsetInBeginSection": 1861, "offsetInEndSection": 2036, "text": " The combination of enhancement patterns on CEUS and serum tumor markers (AFP and CA19-9) may be a potentially specific diagnostic method to differentiate CHC from HCC and CC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29052791", "endSection": "abstract" } ] }, { "body": "Is Miller-Dieker syndrome associated with abnormalities of chromosome 1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18989166", "http://www.ncbi.nlm.nih.gov/pubmed/9063734", "http://www.ncbi.nlm.nih.gov/pubmed/10655551", "http://www.ncbi.nlm.nih.gov/pubmed/11579431", "http://www.ncbi.nlm.nih.gov/pubmed/2740347", "http://www.ncbi.nlm.nih.gov/pubmed/1968707", "http://www.ncbi.nlm.nih.gov/pubmed/29858378", "http://www.ncbi.nlm.nih.gov/pubmed/29628935", "http://www.ncbi.nlm.nih.gov/pubmed/3993677", "http://www.ncbi.nlm.nih.gov/pubmed/10406660", "http://www.ncbi.nlm.nih.gov/pubmed/7573359", "http://www.ncbi.nlm.nih.gov/pubmed/19584063", "http://www.ncbi.nlm.nih.gov/pubmed/2903661", "http://www.ncbi.nlm.nih.gov/pubmed/27644460", "http://www.ncbi.nlm.nih.gov/pubmed/10787042", "http://www.ncbi.nlm.nih.gov/pubmed/28380362", "http://www.ncbi.nlm.nih.gov/pubmed/23326253", "http://www.ncbi.nlm.nih.gov/pubmed/3189330", "http://www.ncbi.nlm.nih.gov/pubmed/29707411", "http://www.ncbi.nlm.nih.gov/pubmed/21239872", "http://www.ncbi.nlm.nih.gov/pubmed/8355785", "http://www.ncbi.nlm.nih.gov/pubmed/6834189", "http://www.ncbi.nlm.nih.gov/pubmed/3963054", "http://www.ncbi.nlm.nih.gov/pubmed/28186603" ], "ideal_answer": [ "No. Miller-Dieker syndrome is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE and leads to malformations during cortical development." ], "exact_answer": "no", "type": "yesno", "id": "5c72f8557c78d69471000080", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29707411", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 332, "text": "Chromosome microdeletions within 17p13.3 can result in either isolated lissencephaly sequence (ILS) or Miller-Dieker syndrome (MDS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29628935", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 876, "text": "We report a fetus with lissencephaly diagnosed as Miller-Dieker Syndrome postnatally. G banded chromosome analysis revealed 45,X,psu dic(17;Y)(p13;p11.32).ish dic (17;Y)(LIS1-,RARA+, SRY+, DYZ3+) by G-banding analysis using high resolution banding technique. Fetal delayed cortical development will be the findings to perform further investigations including fluorescence in situ hybridization analysis for MDS, a 17p13.3 microdeletion syndrome, pre/postnatally. This will be the first case of MDS with unbalanced translocation between deleted short arm of chromosome 17 and Y chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27644460", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 345, "text": " We report the finding of a 2.5-Mb gene region quadruplication of Chromosome 17p13.3. This region is well characterized for the deletion leading to Miller-Dieker syndrome but has an unclear replication phenotype. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29858378", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 1076, "text": "Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3\u03b5) and leads to malformations during cortical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28380362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3993677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2903661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The Miller-Dieker syndrome (type I lissencephaly) is a neuronal migration disorder which is associated with microdeletions in the short arm of chromosome 17.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10787042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2903661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "A 15-month-old girl with Miller-Dieker syndrome, a contiguous gene deletion syndrome involving chromosome 17p13.3 and resulting in lissencephaly, was diagnosed with precursor B-cell acute lymphoblastic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18989166", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 737, "text": "A computed tomography scan revealed evidence of lissencephaly, and chromosomal analysis showed a microdeletion on the short arm of chromosome 17 (17p13.3), confirming the diagnosis as Miller-Dieker syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10787042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3963054", "endSection": "title" }, { "offsetInBeginSection": 848, "offsetInEndSection": 1052, "text": "The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1968707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly (\"smooth brain\"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3189330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2740347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19584063", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1968707", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "HIC1 is a candidate tumor suppressor gene which is frequently hypermethylated in human tumors, and its location within the Miller-Dieker syndrome's critical deletion region at chromosome 17p13.3 makes it a candidate gene for involvement in this gene deletion syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10655551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29707411", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 614, "text": "About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller-Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8355785", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1340, "text": "Chromosome aberrations in which epilepsy is a major and consistent finding include Angelman syndrome due to loss of the maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the 17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf-Hirschhorn syndrome due to deletion of at least the 4p16.3 segment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11579431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Miller-Dieker syndrome and trisomy 5p in a child carrying a derivative chromosome with a microdeletion in 17p13.3 telomeric to the LIS1 and the D17S379 loci.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10406660", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The Miller-Dieker syndrome, a disorder of neuronal migration, is caused by deletions of chromosome 17p13.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7573359", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 781, "text": "The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome.The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2903661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19584063", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "Unbalanced translocation (15;17)(q13;13.3) with apparent Prader-Willi syndrome but without Miller-Dieker syndrome.We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3993677", "endSection": "title" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1227, "text": "The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1968707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3.Miller-Dieker syndrome (MDS) is a multiple malformation syndrome characterized by classical lissencephaly and a characteristic facies. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9063734", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Case Report of Proliferative Peripheral Retinopathy in Two Familial Lissencephaly Infants with Miller-Dieker Syndrome.A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29707411", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.Profilin is a conserved actin-monomer-binding protein which is found in all eukaryotes, including yeast. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1968707", "endSection": "title" }, { "offsetInBeginSection": 380, "offsetInEndSection": 600, "text": "We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3993677", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 533, "text": "A review of the literature revealed five additional patients in three families, who had Miller-Dieker syndrome and an abnormality of 17p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6834189", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 596, "text": "We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3993677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Miller-Dieker syndrome: lissencephaly and monosomy 17p.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6834189", "endSection": "title" }, { "offsetInBeginSection": 534, "offsetInEndSection": 639, "text": "Thus, we propose that monosomy of distal 17p may be the cause of Miller-Dieker syndrome in some patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6834189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Miller-Dieker syndrome with der(17)t(12;17)(q24.33;p13.3)pat presenting with a potential risk of mis-identification as a de novo submicroscopic deletion of 17p13.3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21239872", "endSection": "title" }, { "offsetInBeginSection": 407, "offsetInEndSection": 486, "text": "Most cases of Miller-Dieker syndrome have a de novo deletion involving 17p13.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21239872", "endSection": "abstract" } ] }, { "body": "List clinical symptoms of the MECOM-associated syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29540340" ], "ideal_answer": [ "Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. The clinical picture included radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal malformations, B-cell deficiency, and presenile hearing loss. No single clinical manifestation was detected in all patients affected by MECOM mutations. Radioulnar synostosis and B-cell deficiency were observed only in patients with mutations affecting a short region in the C-terminal zinc finger domain of EVI1." ], "exact_answer": [ [ "radioulnar synostosis" ], [ "bone marrow failure" ], [ "clinodactyly" ], [ "cardiac malformations" ], [ "renal malformations" ], [ "B-cell deficiency" ], [ "presenile hearing loss" ] ], "type": "list", "id": "5c63286ae842deac6700000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540340", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1325, "text": "Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. Here we report on 12 patients with congenital hypomegakaryocytic thrombocytopenia caused by MECOM mutations (including 10 novel mutations). The mutations affected different functional domains of the EVI1 protein. The spectrum of phenotypes was much broader than initially reported for the first 3 patients; we found familial as well as sporadic cases, and the clinical spectrum ranged from isolated radioulnar synostosis with no or mild hematological involvement to severe bone marrow failure without obvious skeletal abnormality. The clinical picture included radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal malformations, B-cell deficiency, and presenile hearing loss. No single clinical manifestation was detected in all patients affected by MECOM mutations. Radioulnar synostosis and B-cell deficiency were observed only in patients with mutations affecting a short region in the C-terminal zinc finger domain of EVI1. We propose the term MECOM-associated syndrome for this heterogeneous hereditary disease and inclusion of MECOM sequencing in the diagnostic workup of congenital bone marrow failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540340", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1143, "text": "Radioulnar synostosis and B-cell deficiency were observed only in patients with mutations affecting a short region in the C-terminal zinc finger domain of EVI1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540340", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 723, "text": "The spectrum of phenotypes was much broader than initially reported for the first 3 patients; we found familial as well as sporadic cases, and the clinical spectrum ranged from isolated radioulnar synostosis with no or mild hematological involvement to severe bone marrow failure without obvious skeletal abnormality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540340", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 891, "text": "The clinical picture included radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal malformations, B-cell deficiency, and presenile hearing loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540340", "endSection": "abstract" } ] }, { "body": "Does the interaction of MOV10 and RNASEH2 promote L1 retrotransposition?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29315404" ], "ideal_answer": [ "MOV10 interacts with RNASEH2, and their interplay is crucial for restricting L1 retrotransposition." ], "exact_answer": "no", "type": "yesno", "id": "5c93e6a1ecadf2e73f00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Interplay between RNASEH2 and MOV10 controls LINE-1 retrotransposition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29315404", "endSection": "title" }, { "offsetInBeginSection": 661, "offsetInEndSection": 774, "text": "We show that MOV10 interacts with RNASEH2, and their interplay is crucial for restricting L1 retrotransposition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29315404", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1423, "text": "Furthermore, we show that RNASEH2-MOV10-mediated L1 restriction downregulates expression of the rheumatoid arthritis-associated inflammatory cytokines and matrix-degrading proteinases in synovial cells, implicating a potential causal relationship between them and disease development in terms of disease predisposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29315404", "endSection": "abstract" } ] }, { "body": "What is the role of CD28 with respect to bacterial superantigen toxins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24022021", "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "http://www.ncbi.nlm.nih.gov/pubmed/30404186" ], "ideal_answer": [ "CD28 is a direct receptor of bacterial superantigen toxins.", "cd28 is a homodimer expressed on t cells that functions as the principal costimulatory ligand in the immune response" ], "type": "summary", "id": "5c72bd967c78d69471000078", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "abstract" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1533, "text": "The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 734, "text": "Our finding that CD28 is a direct receptor of superantigen toxins broadens the scope of microbial pathogen recognition mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24022021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "CD28: direct and critical receptor for superantigen toxins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24022021", "endSection": "title" }, { "offsetInBeginSection": 409, "offsetInEndSection": 746, "text": "The need to protect from superantigen toxins led to our discovery that in addition to the well-known MHC class II and T cell receptors, the principal costimulatory receptor, CD28, and its constitutively expressed coligand, B7-2 (CD86), previously thought to have only costimulatory function, are actually critical superantigen receptors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404186", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1418, "text": "Structural analysis showed that when a superantigen binds to the T cell receptor on the T cell and major histocompatibility class II molecule on the antigen-presenting cell, CD28 can be accommodated readily as third superantigen receptor in the quaternary complex, with the CD28 dimer interface oriented towards the \u03b2-strand/hinge/\u03b1-helix domain in the superantigen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 793, "text": "Our finding that CD28 is a direct receptor of superantigen toxins broadens the scope of microbial pathogen recognition mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24022021", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1669, "text": "The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock.Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "title" }, { "offsetInBeginSection": 122, "offsetInEndSection": 435, "text": "CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response through an interaction with its B7 coligands, yet we show here that to elicit inflammatory cytokine gene expression and toxicity, superantigens must bind directly into the dimer interface of CD28.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1382, "text": "Our findings identify the CD28 homodimer interface as a critical receptor target for superantigens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "abstract" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1537, "text": "The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21931534", "endSection": "abstract" } ] }, { "body": "What is the exoproteome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28137564", "http://www.ncbi.nlm.nih.gov/pubmed/29233035", "http://www.ncbi.nlm.nih.gov/pubmed/29419372" ], "ideal_answer": [ "Exoproteomics aims at describing and quantifying the proteins found outside of the cells." ], "exact_answer": [ "secreted protein content" ], "type": "factoid", "id": "5c8cd26a0101eac870000003", "snippets": [ { "offsetInBeginSection": 234, "offsetInEndSection": 408, "text": "Exoproteomics aims at describing and quantifying the proteins found outside of the cells, thus takes advantage of the most recent methodologies of next-generation proteomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28137564", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 1107, "text": "Since the extracellular proteome of bacterial pathogens is a reservoir of virulence factors, the exoproteomes of the staphylococcal isolates in monoculture and co-culture with B. thuringiensis and K. oxytoca were characterized by Mass Spectrometry to explore the inherent relationships between these co-exisiting bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233035", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 841, "text": " Comparative analyses of the secreted protein content (exoproteome) revealed that many enzymes involved in carbohydrate hydrolysis were regulated by VdSec22 or VdSso1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29419372", "endSection": "abstract" } ] }, { "body": "List features of the Triple A syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30069287", "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "http://www.ncbi.nlm.nih.gov/pubmed/29874194", "http://www.ncbi.nlm.nih.gov/pubmed/18551317", "http://www.ncbi.nlm.nih.gov/pubmed/12530689", "http://www.ncbi.nlm.nih.gov/pubmed/29255950", "http://www.ncbi.nlm.nih.gov/pubmed/21656342", "http://www.ncbi.nlm.nih.gov/pubmed/27895694", "http://www.ncbi.nlm.nih.gov/pubmed/22000320", "http://www.ncbi.nlm.nih.gov/pubmed/11196451", "http://www.ncbi.nlm.nih.gov/pubmed/12429595", "http://www.ncbi.nlm.nih.gov/pubmed/11815731", "http://www.ncbi.nlm.nih.gov/pubmed/23691407", "http://www.ncbi.nlm.nih.gov/pubmed/12752575", "http://www.ncbi.nlm.nih.gov/pubmed/15666842", "http://www.ncbi.nlm.nih.gov/pubmed/16970037" ], "ideal_answer": [ "Triple A (Allgrove) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency, achalasia, and alacrimia. It is frequently associated with neurological manifestations like polyneuropathy." ], "exact_answer": [ [ "adrenal insufficiency" ], [ "achalasia" ], [ "alacrimia" ] ], "type": "list", "id": "5c72fb4a7c78d69471000082", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Triple A syndrome (TAS) or Allgrove syndrome (OMIM #231550) is a rare autosomal recessive disorder characterised by adrenocorticotropic hormone-resistant adrenal insufficiency, alacrima, achalasia, and neurological and dermatological abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Background Triple A syndrome is characterized by achalasia, alacrima and adrenal insufficiency with neurological manifestations occurring later in the course of the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29874194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Allgrove or triple A syndrome (AS or AAA) is a rare autosomal recessive syndrome with variable phenotype due to mutations in AAAS gene which encodes a protein called ALADIN. Generally, it's characterized by of adrenal insufficiency in consequence of adrenocorticotropic hormone (ACTH) resistance, besides of achalasia, and alacrimia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30069287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Triple-A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder. The 3 features of this syndrome are achalasia, adrenal insufficiency, and alacrima. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27895694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Allgrove (Triple A) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrimia. It is frequently associated with neurological manifestations like polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "\"Triple A\" syndrome is a rare, autosomal recessive condition whose main clinical features are alacrima, achalasia, and adrenal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22000320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The triple A or Allgrove syndrome is an autosomal-recessive disease (MIM*231550) characterized by the triad of achalasia, alacrima and adrenocorticotropic hormone (ACTH)-resistant adrenal insufficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12752575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The triple A syndrome is a rare autosomal recessive disease that is characterised by the triad of adrenocorticotropin (ACTH)-resistant adrenal insufficiency, achalasia and alacrima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18551317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "BACKGROUND\nThe triple A syndrome is characterized by the main features adrenal insufficiency, achalasia and alacrima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11815731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Allgrove syndrome (triple A syndrome) is a rare autosomal recessive disorder characterized by achalasia, alacrima, adrenal insufficiency, and--occasionally--autonomic instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16970037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "The triple A syndrome (MIM*231550) is a rare autosomal recessive disorder characterized by adrenocorticotropic hormone (ACTH) resistant adrenal failure, achalasia, alacrima and a variety of neurological and dermatological features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12530689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The triple A syndrome (MIM#231550) is a rare autosomal recessive disorder characterized by adrenocorticotropic hormone (ACTH) resistant adrenal failure, achalasia, alacrima, and a variety of neurological and dermatological features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15666842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Triple A syndrome is an autosomal recessive disorder characterized by the triad of adrenocorticotropic hormone resistant adrenal insufficiency, achalasia, and alacrima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23691407", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 399, "text": "The triple A syndrome is caused by mutations in the AAAS gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insufficiency Neurologic disorder).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15666842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The triple A syndrome or Allgrove syndrome (MIM*231550) is characterized by adrenocorticotropic hormone (ACTH) resistant Adrenal insufficiency, Achalasia of the cardia and Alacrima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11196451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Triple A (Allgrove) syndrome is characterized by achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12429595", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 657, "text": "Two months later, achalasia was diagnosed, and in the presence of alacrima, the patient satisfies the diagnostic criteria of triple A syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18551317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Clinical and genetic characterization of families with triple A (Allgrove) syndrome.Triple A (Allgrove) syndrome is characterized by achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12429595", "endSection": "title" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1428, "text": "Those bearing mutations had the classical triple A syndrome of achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12429595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Clinical and molecular genetic findings in a 6-year-old Bosnian boy with triple A syndrome.The triple A syndrome is a rare autosomal recessive disease that is characterised by the triad of adrenocorticotropin (ACTH)-resistant adrenal insufficiency, achalasia and alacrima. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18551317", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Triple A syndrome: genotype-phenotype assessment.The triple A or Allgrove syndrome is an autosomal-recessive disease (MIM*231550) characterized by the triad of achalasia, alacrima and adrenocorticotropic hormone (ACTH)-resistant adrenal insufficiency. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12752575", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Neurological features in adult Triple-A (Allgrove) syndrome.Triple-A or Allgrove syndrome is a rare multisystem disease classically associated with esophageal achalasia, adrenal insufficiency and alacrima. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21656342", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Triple A syndrome is a rare, autosomal recessive condition whose main clinical features are alacrima, achalasia, and adrenal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22000320", "endSection": "abstract" } ] }, { "body": "What is the mechanism of the drug CRT0066101?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29071385", "http://www.ncbi.nlm.nih.gov/pubmed/25852060", "http://www.ncbi.nlm.nih.gov/pubmed/29270134", "http://www.ncbi.nlm.nih.gov/pubmed/26797128", "http://www.ncbi.nlm.nih.gov/pubmed/27030010", "http://www.ncbi.nlm.nih.gov/pubmed/20442301", "http://www.ncbi.nlm.nih.gov/pubmed/20947701", "http://www.ncbi.nlm.nih.gov/pubmed/26895471" ], "ideal_answer": [ "Recently developed small molecule PKD inhibitors, CID755673 and CRT0066101, provide potentially important pharmacological approaches to further investigate the effect of PKD in pancreatitis therapy", "CRT0066101 inhibits protein kinase D" ], "type": "summary", "id": "5c83ff91617e120c34000005", "snippets": [ { "offsetInBeginSection": 372, "offsetInEndSection": 569, "text": "Recently developed small molecule PKD inhibitors, CID755673 and CRT0066101, provide potentially important pharmacological approaches to further investigate the effect of PKD in pancreatitis therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29270134", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 206, "text": "CRT0066101, an inhibitor of PKD, has antitumor activity in multiple types of carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29071385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Protein kinase D inhibitor CRT0066101 ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29071385", "endSection": "title" }, { "offsetInBeginSection": 840, "offsetInEndSection": 933, "text": "Inhibitors of PKD (CRT0066101) and G\u03b2\u03b3 (gallein) prevented PAR2-stimulated activation of PKD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27030010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25852060", "endSection": "title" }, { "offsetInBeginSection": 1552, "offsetInEndSection": 1624, "text": "In conclusion, CRT0066101 is a potent and specific PKD family inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20947701", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 381, "text": "Our PKD inhibitor discovery program identified CRT0066101 as a specific inhibitor of all PKD isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442301", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 948, "text": "This identifies ER(-) breast cancers as ideal for treatment with the PKD inhibitor CRT0066101.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25852060", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 570, "text": "Recently developed small molecule PKD inhibitors, CID755673 and CRT0066101, provide potentially important pharmacological approaches to further investigate the effect of PKD in pancreatitis therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29270134", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1184, "text": "Serine phosphorylation and inhibition of AMPK activity were partially prevented by the broad PKC inhibitor G\u00f66983 and fully prevented by the specific PKD1 inhibitor CRT0066101.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26797128", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 573, "text": "For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20947701", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1102, "text": "Furthermore, we confirmed that the PRKD1 inhibitor CRT0066101 reduced phosphorylated PKD/PKC\u03bc, leading to suppression of breast cancer stemness through GSK3/\u03b2-catenin signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26895471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29071385", "endSection": "title" }, { "offsetInBeginSection": 313, "offsetInEndSection": 463, "text": "For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20947701", "endSection": "abstract" }, { "offsetInBeginSection": 1836, "offsetInEndSection": 2037, "text": "Our results show for the first time that a PKD-specific small-molecule inhibitor CRT0066101 blocks pancreatic cancer growth in vivo and show that PKD is a novel therapeutic target in pancreatic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442301", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 962, "text": "Furthermore, we confirmed that the PRKD1 inhibitor CRT0066101 reduced phosphorylated PKD/PKC\u03bc, leading to suppression of breast cancer stemness through GSK3/\u03b2-catenin signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26895471", "endSection": "abstract" } ] }, { "body": "Which protein is the Mitochondrial carrier homolog 2 (MTCH2) receptor for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30401654", "http://www.ncbi.nlm.nih.gov/pubmed/22326460", "http://www.ncbi.nlm.nih.gov/pubmed/26794447", "http://www.ncbi.nlm.nih.gov/pubmed/15899861", "http://www.ncbi.nlm.nih.gov/pubmed/27320914" ], "ideal_answer": [ "Mitochondrial Carrier Homolog 2 (MTCH2) acts as a receptor for the BH3 interacting-domain death agonist (BID) in the mitochondrial outer membrane." ], "exact_answer": [ "truncated BH3-interacting domain death agonist (tBID) protein" ], "type": "factoid", "id": "5c8cdfe50101eac870000004", "snippets": [ { "offsetInBeginSection": 1148, "offsetInEndSection": 1211, "text": "These results implicate Mtch2 as a mitochondrial target of tBID", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15899861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Mitochondrial Carrier Homolog 2 (MTCH2) acts as a receptor for the BH3 interacting-domain death agonist (BID) in the mitochondrial outer membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30401654", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 524, "text": "MTCH2, a proposed receptor for tBID", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26794447", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 362, "text": "tBid recruitment to mitochondria, which is facilitated by its receptor MTCH2 at the outer mitochondrial membrane (OMM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27320914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Recent studies report mitochondrial carrier homolog 2 (MTCH2) as a novel and uncharacterized protein that acts as a receptor-like protein for the truncated BH3-interacting domain death agonist (tBID) protein in the outer membrane of mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22326460", "endSection": "abstract" } ] }, { "body": "What is PhenomeCentral?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26251998" ], "ideal_answer": [ "The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. The PhenomeCentral portal (https://phenomecentral.org) enables the secure sharing of case records by clinicians and rare disease scientists. PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking. Users can then contact other submitters to follow up on promising matches. PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists. Though the majority of these records have associated exome data, most lack a molecular diagnosis. PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered." ], "type": "summary", "id": "5c642fbce842deac67000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "PhenomeCentral: a portal for phenotypic and genotypic matchmaking of patients with rare genetic diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26251998", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1457, "text": "The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. To enable the secure sharing of case records by clinicians and rare disease scientists, we have developed the PhenomeCentral portal (https://phenomecentral.org). Each record includes a phenotypic description and relevant genetic information (exome or candidate genes). PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking. Users can then contact other submitters to follow up on promising matches. PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists. Though the majority of these records have associated exome data, most lack a molecular diagnosis. PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26251998", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 785, "text": "PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26251998", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1457, "text": "PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26251998", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 401, "text": "To enable the secure sharing of case records by clinicians and rare disease scientists, we have developed the PhenomeCentral portal (https://phenomecentral.org).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26251998", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1142, "text": "PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26251998", "endSection": "abstract" } ] }, { "body": "What organism causes Rhombencephalitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24050079", "http://www.ncbi.nlm.nih.gov/pubmed/28730571", "http://www.ncbi.nlm.nih.gov/pubmed/9250779", "http://www.ncbi.nlm.nih.gov/pubmed/20204066", "http://www.ncbi.nlm.nih.gov/pubmed/16126275", "http://www.ncbi.nlm.nih.gov/pubmed/21956758", "http://www.ncbi.nlm.nih.gov/pubmed/28166691", "http://www.ncbi.nlm.nih.gov/pubmed/30328643", "http://www.ncbi.nlm.nih.gov/pubmed/30413440", "http://www.ncbi.nlm.nih.gov/pubmed/27818548", "http://www.ncbi.nlm.nih.gov/pubmed/15765316", "http://www.ncbi.nlm.nih.gov/pubmed/3579687", "http://www.ncbi.nlm.nih.gov/pubmed/23035165" ], "ideal_answer": [ "Rhombencephalitis caused by Listeria monocytogenes", "Rhombencephalitis is caused by Listeria monocytogenes" ], "exact_answer": [ "Listeria monocytogenes" ], "type": "factoid", "id": "5c84346b75a4a5d219000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Rhombencephalitis caused by Listeria monocytogenes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28166691", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Listeria rhombencephalitis is caused by infection with Listeria monocytogenes and is associated with a high mortality rate in humans and ruminants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30328643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "A pastured 2-y-old cross-breed bull developed brainstem encephalitis (rhombencephalitis); Listeria monocytogenes was isolated from the brai", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28166691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Listeria monocytogenes is associated with rhombencephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28730571", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 328, "text": "Infection with bacteria of the genus Listeria is the most common cause of rhombencephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27818548", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 225, "text": "Listeria rhombencephalitis is a rare but well-defined clinical syndrome of lower brain-stem involvement caused by Listeria monocytogenes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3579687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "INTRODUCTION\nListeria monocytogenes is a gram-positive bacillus which causes sporadic infections in immunocompromised humans, with a special propensity for the central nervous system, in the form of acute, subacute or chronic meningitis, rhombencephalitis or abscesses in the brain or spinal cord.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15765316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Listeria monocytogenes is a gram-positive bacillus that exhibits predilection to infect the central nervous system in immunocompromised individuals; the most common manifestations are meningitis and rhombencephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24050079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Listeria rhombencephalitis is caused by infection with Listeria monocytogenes and is associated with a high mortality rate in humans and ruminants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30328643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Rhombencephalitis Caused by Listeria monocytogenes in Humans and Ruminants: A Zoonosis on the Rise?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20204066", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Rhombencephalitis due to Listeria monocytogenes is a frequent complication of human listeriosis, inducing a high mortality and severe neurological sequelae despite antibiotic therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9250779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Rapid detection of Listeria monocytogenes rhombencephalitis in an immunocompetent patient by multiplexed PCR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413440", "endSection": "title" }, { "offsetInBeginSection": 416, "offsetInEndSection": 467, "text": "Listeria is the most common cause of infectious RE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21956758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Listeria monocytogenes brain abscess: two cases and review of the literature.Listeria monocytogenes is a gram-positive bacillus that exhibits predilection to infect the central nervous system in immunocompromised individuals; the most common manifestations are meningitis and rhombencephalitis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24050079", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "A case of rhombencephalitis caused by Listeria monocytogenes successfully treated with linezolid.Infection of the central nervous system due to Listeria monocytogenes is uncommon. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126275", "endSection": "title" }, { "offsetInBeginSection": 122, "offsetInEndSection": 246, "text": "We describe in this report a case of rhombencephalitis caused by Listeria monocytogenes successfully treated with linezolid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "A case of rhombencephalitis caused by Listeria monocytogenes successfully treated with linezolid.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16126275", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "A gerbil model for rhombencephalitis due to Listeria monocytogenes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9250779", "endSection": "title" }, { "offsetInBeginSection": 329, "offsetInEndSection": 393, "text": "Primary rhombencephalitis caused by infection with Listeria spp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27818548", "endSection": "abstract" } ] }, { "body": "Has the protein SIRT2 been associated to cervical cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25794641", "http://www.ncbi.nlm.nih.gov/pubmed/28776959" ], "ideal_answer": [ "Yes.\nA progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal\u2009<\u2009preneoplasia\u2009<\u2009cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5c8cfca70101eac870000005", "snippets": [ { "offsetInBeginSection": 856, "offsetInEndSection": 1013, "text": " A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal\u2009<\u2009preneoplasia\u2009<\u2009cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794641", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 808, "text": " We demonstrate that treatment of cervical cancer cells with a RhoGDI\u03b1-derived K52-trifluoroacetylated, substrate-derived peptidic sirtuin inhibitor severely impairs cell proliferation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28776959", "endSection": "abstract" } ] }, { "body": "Which receptor is targeted by Erenumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29406534", "http://www.ncbi.nlm.nih.gov/pubmed/28835404", "http://www.ncbi.nlm.nih.gov/pubmed/29263689", "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "http://www.ncbi.nlm.nih.gov/pubmed/28460892", "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "http://www.ncbi.nlm.nih.gov/pubmed/30409109", "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "http://www.ncbi.nlm.nih.gov/pubmed/29878340", "http://www.ncbi.nlm.nih.gov/pubmed/30086681" ], "ideal_answer": [ "Erenumab is a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention." ], "exact_answer": [ "calcitonin gene-related peptide receptor" ], "type": "factoid", "id": "5c73acef7c78d69471000088", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Erratum: Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab [Corrigendum].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29406534", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 237, "text": "Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1379, "text": "Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29263689", "endSection": "title" }, { "offsetInBeginSection": 448, "offsetInEndSection": 573, "text": "Erenumab is the only mAb that targets the CGRP receptor instead of the ligand, with high specificity and affinity of binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29263689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND\nWe tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 248, "text": "We assessed the efficacy and safety of erenumab, a fully human monoclonal antibody against the CGRP receptor, in patients with chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28460892", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 211, "text": "Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1378, "text": "Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 257, "text": "Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "OBJECTIVE\nTo assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28835404", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 777, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 499, "text": "Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Amgen and Novartis are developing erenumab (AIMOVIG\u2122, erenumab-aooe)-a fully human monoclonal antibody calcitonin gene-related peptide (CGRP) receptor antagonist-for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "OBJECTIVE\nTo determine the potential impact of erenumab, a human anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise-induced angina, and ST depression in a double-blind, placebo-controlled study in patients with stable angina due to documented coronary artery disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29878340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Background We evaluated the effect of erenumab, a fully human monoclonal antibody that inhibits the canonical calcitonin gene-related peptide receptor, on migraine-related disability, impact, and health-related quality of life among patients with episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30086681", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 552, "text": "METHODS\nThirteen migraine patients, previously enrolled in erenumab anti-CGRP receptor monoclonal antibody trials, received CGRP in a double-blind, placebo-controlled, randomized cross-over design to investigate their susceptibility to migraine induction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30409109", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 594, "text": "Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" }, { "offsetInBeginSection": 1593, "offsetInEndSection": 1789, "text": "Erenumab did not adversely affect exercise time in a high cardiovascular risk population of patients, supporting that inhibition of the canonical CGRP receptor does not worsen myocardial ischemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29878340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "To determine the potential impact of erenumab, a human anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise-induced angina, and ST depression in a double-blind, placebo-controlled study in patients with stable angina due to documented coronary artery disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29878340", "endSection": "abstract" } ] }, { "body": "Are recessive coding variants responsible for the majority of undiagnosed nonconsanguineous individuals?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30409806" ], "ideal_answer": [ "No. It is suggested that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration." ], "exact_answer": "no", "type": "yesno", "id": "5c6438a5e842deac67000016", "snippets": [ { "offsetInBeginSection": 629, "offsetInEndSection": 879, "text": "Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30409806", "endSection": "abstract" } ] }, { "body": "How can super-enhancers be used in disease diagnosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26438538" ], "ideal_answer": [ "Super-enhancers are clusters of transcriptional enhancers that drive cell-type-specific gene expression and are crucial to cell identity. Many disease-associated sequence variations are enriched in super-enhancer regions of disease-relevant cell types. Thus, super-enhancers can be used as potential biomarkers for disease diagnosis and therapeutics. Current studies have identified super-enhancers in more than 100 cell types and demonstrated their functional importance." ], "type": "summary", "id": "5c8962e8d558e5f232000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "Super-enhancers are clusters of transcriptional enhancers that drive cell-type-specific gene expression and are crucial to cell identity. Many disease-associated sequence variations are enriched in super-enhancer regions of disease-relevant cell types. Thus, super-enhancers can be used as potential biomarkers for disease diagnosis and therapeutics. Current studies have identified super-enhancers in more than 100 cell types and demonstrated their functional importance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26438538", "endSection": "abstract" } ] }, { "body": "List sirtuin inhibitors.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30066578", "http://www.ncbi.nlm.nih.gov/pubmed/29330215", "http://www.ncbi.nlm.nih.gov/pubmed/28254776", "http://www.ncbi.nlm.nih.gov/pubmed/26722027", "http://www.ncbi.nlm.nih.gov/pubmed/29235227", "http://www.ncbi.nlm.nih.gov/pubmed/29659581" ], "ideal_answer": [ "Sirtinol\nnicotinamide (NAM)\nLC-0296\nBZD9L1" ], "exact_answer": [ [ "Sirtinol" ], [ "nicotinamide (NAM)" ], [ "LC-0296" ], [ "BZD9L1" ] ], "type": "list", "id": "5c8d00980101eac870000006", "snippets": [ { "offsetInBeginSection": 1073, "offsetInEndSection": 1121, "text": " Sirtinol, a commonly employed sirtuin inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29235227", "endSection": "abstract" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1619, "text": "sirtuin inhibitor nicotinamide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330215", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 393, "text": " pan-sirtuin inhibitor nicotinamide (NAM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29659581", "endSection": "abstract" }, { "offsetInBeginSection": 55, "offsetInEndSection": 93, "text": "of a novel sirtuin inhibitor (BZD9L1) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30066578", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1250, "text": " Sirtuin inhibitor nicotinamide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28254776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 36, "text": "A Novel Sirtuin-3 Inhibitor, LC-0296", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26722027", "endSection": "title" } ] }, { "body": "Is the NLM medical text indexer (MTI) still useful and relevant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28231809" ], "ideal_answer": [ "Yes. The NLM Medical Text Indexer (MTI) is still relevant and useful, and needs to be improved and expanded. The BioASQ Challenge results have shown that more machine learning needs to be incorporated into MTI while still retaining the indexing rules that have earned MTI the indexers' trust over the years. MTI also needs to be expanded through the use of full text, when and where it is available, to provide coverage of indexing terms that are typically only found in the full text." ], "exact_answer": "yes", "type": "yesno", "id": "5c6445f0e842deac67000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "12 years on - Is the NLM medical text indexer still useful and relevant?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 2174, "text": "Facing a growing workload and dwindling resources, the US National Library of Medicine (NLM) created the Indexing Initiative project in 1996. This cross-library team's mission is to explore indexing methodologies for ensuring quality and currency of NLM document collections. The NLM Medical Text Indexer (MTI) is the main product of this project and has been providing automated indexing recommendations since 2002. After all of this time, the questions arise whether MTI is still useful and relevant.METHODS: To answer the question about MTI usefulness, we track a wide variety of statistics related to how frequently MEDLINE indexers refer to MTI recommendations, how well MTI performs against human indexing, and how often MTI is used. To answer the question of MTI relevancy compared to other available tools, we have participated in the 2013 and 2014 BioASQ Challenges. The BioASQ Challenges have provided us with an unbiased comparison between the MTI system and other systems performing the same task.RESULTS: Indexers have continually increased their use of MTI recommendations over the years from 15.75% of the articles they index in 2002 to 62.44% in 2014 showing that the indexers find MTI to be increasingly useful. The MTI performance statistics show significant improvement in Precision (+0.2992) and F1 (+0.1997) with modest gains in Recall (+0.0454) over the years. MTI consistency is comparable to the available indexer consistency studies. MTI performed well in both of the BioASQ Challenges ranking within the top tier teams.CONCLUSIONS: Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded. The BioASQ Challenge results have shown that we need to incorporate more machine learning into MTI while still retaining the indexing rules that have earned MTI the indexers' trust over the years. We also need to expand MTI through the use of full text, when and where it is available, to provide coverage of indexing terms that are typically only found in the full text. The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 2048, "offsetInEndSection": 2179, "text": "The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1675, "text": "CONCLUSIONS\nBased on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "12 years on - Is the NLM medical text indexer still useful and relevant?Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "title" }, { "offsetInBeginSection": 545, "offsetInEndSection": 676, "text": "The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 769, "text": "After all of this time, the questions arise whether MTI is still useful and relevant.
METHODS: To answer the question about MTI usefulness, we track a wide variety of statistics related to how frequently MEDLINE indexers refer to MTI recommendations, how well MTI performs against human indexing, and how often MTI is used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 1270, "offsetInEndSection": 1482, "text": "The MTI performance statistics show significant improvement in Precision (+0.2992) and F
CONCLUSIONS: Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 1855, "offsetInEndSection": 1990, "text": "The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 502, "text": "After all of this time, the questions arise whether MTI is still useful and relevant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 2003, "offsetInEndSection": 2134, "text": "The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1630, "text": "Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28231809", "endSection": "abstract" } ] }, { "body": "Has strimvelis been approved by the European Medicines Agency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29625577" ], "ideal_answer": [ "Yes, the gene therapy Strimvelis has been approved by the European Medicines Agency." ], "exact_answer": "yes", "type": "yesno", "id": "5c8972d4d558e5f232000006", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 342, "text": "Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625577", "endSection": "abstract" } ] }, { "body": "What antibiotic is currently used as the standard of care for Clostridium Difficile infection as of 2018", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27601193", "http://www.ncbi.nlm.nih.gov/pubmed/28009682" ], "ideal_answer": [ "fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection. fidaxomicin is a new antibiotic used to treat clostridium difficile infection (cdi).", "Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection. Fidaxomicin is a new antibiotic used to treat Clostridium difficile infection (CDI).", "Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection.Fidaxomicin is a new antibiotic used to treat Clostridium difficile infection (CDI)", "Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent fidaxomicin" ], "exact_answer": [ "Fidaxomicin" ], "type": "factoid", "id": "5c85234775a4a5d219000007", "snippets": [ { "offsetInBeginSection": 156, "offsetInEndSection": 295, "text": " Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27601193", "endSection": "abstract" }, { "offsetInBeginSection": 22, "offsetInEndSection": 107, "text": "Fidaxomicin is a new antibiotic used to treat Clostridium difficile infection (CDI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28009682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Outcomes With Fidaxomicin Therapy in Clostridium difficile Infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28009682", "endSection": "title" } ] }, { "body": "Which proteins are markers of HPV oncogenic activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28811834", "http://www.ncbi.nlm.nih.gov/pubmed/16445657", "http://www.ncbi.nlm.nih.gov/pubmed/18202795", "http://www.ncbi.nlm.nih.gov/pubmed/25708613", "http://www.ncbi.nlm.nih.gov/pubmed/27739439" ], "ideal_answer": [ "p16INK4a (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions." ], "type": "summary", "id": "5c8d0a980101eac870000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Overexpression of p16 INK4a as an indicator for human papillomavirus oncogenic activity in cervical squamous neoplasia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16445657", "endSection": "title" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1292, "text": "Using p16(INK4a) as a bio marker of HPV oncogenic activity, we demonstrate that the level of pRb dysfunction by high-risk HPV varied from subtypes and was getting more frequent from CIN2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16445657", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1685, "text": "While no stand-alone test was sufficiently accurate for classifying HPV-associated OPSCC, the high sensitivity and specificity of the established combination of p16 immunostain, DNA ISH, and HPV16 DNA amplification suggests that the introduction of labour- and cost-intensive mRNA ISH, is not necessary in the diagnostic routine of oropharyngeal tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25708613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "p16INK4a (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27739439", "endSection": "abstract" } ] }, { "body": "Which features are evaluated with the CRAFFT screening test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21466499", "http://www.ncbi.nlm.nih.gov/pubmed/28850302", "http://www.ncbi.nlm.nih.gov/pubmed/29282234", "http://www.ncbi.nlm.nih.gov/pubmed/23183686", "http://www.ncbi.nlm.nih.gov/pubmed/25727823" ], "ideal_answer": [ "The CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) was developed as a brief screening instrument for adolescents to measure Alcohol and other substance use disorders." ], "exact_answer": [ [ "Car" ], [ "Relax" ], [ "Alone" ], [ "Forget" ], [ "Friends" ], [ "Trouble" ] ], "type": "list", "id": "5c73acf57c78d6947100008c", "snippets": [ { "offsetInBeginSection": 111, "offsetInEndSection": 512, "text": " The New Mexico Department of Health school-based health centers (SBHCs) universally administer a validated screen, the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), for adolescent substance use concerns; however, quality assurance efforts revealed that SBHC providers needed more information at the point of screening to initiate brief interventions for students with positive CRAFFT screens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28850302", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 623, "text": "We present the results of the reliability and concurrent validity of the CRAFFT (acronym for Car, Relax, Alone, Forget, Friends, and Trouble) substance abuse screening instrument among residents of youth correctional facilities in Lagos, Nigeria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29282234", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 404, "text": "The Problem Oriented Screening Instrument for Teenagers (POSIT) and the Car, Relax, Alone, Forget, Family/Friends, Trouble questionnaire (CRAFFT) are used to this end.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25727823", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 427, "text": "The aim of this study was to compare the performance of the Alcohol Use Disorders Identification Test (AUDIT), its short form AUDIT-C, the Substance Module of the Problem Oriented Screening Instrument for Teenagers (POSIT), and CRAFFT (acronym for car, relax, alone, forget, family, and friends).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23183686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "INTRODUCTION: Alcohol (AUD) and other substance use disorders (SUD) are common among adolescents. The CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble, 1999) was developed as a brief screening instrument for adolescents to measure AUD and SUD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21466499", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 403, "text": "The Problem Oriented Screening Instrument for Teenagers (POSIT) and the Car, Relax, Alone, Forget, Family/Friends, Trouble questionnaire (CRAFFT) are used to this end.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25727823", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 245, "text": "The CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble, 1999) was developed as a brief screening instrument for adolescents to measure AUD and SUD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21466499", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 622, "text": "We present the results of the reliability and concurrent validity of the CRAFFT (acronym for Car, Relax, Alone, Forget, Friends, and Trouble) substance abuse screening instrument among residents of youth correctional facilities in Lagos, Nigeria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29282234", "endSection": "abstract" } ] }, { "body": "Describe the bartender algorithm", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29069318" ], "ideal_answer": [ "Barcode sequencing (bar-seq) is a high-throughput, and cost effective method to assay large numbers of cell lineages or genotypes in complex cell pools. Because of its advantages, applications for bar-seq are quickly growing-from using neutral random barcodes to study the evolution of microbes or cancer, to using pseudo-barcodes, such as shRNAs or sgRNAs to simultaneously screen large numbers of cell perturbations. Bartender is an accurate clustering algorithm to detect barcodes and their abundances from raw next-generation sequencing data. It comprises a set of simple-to-use command line tools that can be performed on a laptop at comparable run times to existing methods. Bartender is available at no charge for non-commercial use at https://github.com/LaoZZZZZ/bartender-1.1" ], "type": "summary", "id": "5c65ae757c78d6947100000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Bartender: a fast and accurate clustering algorithm to count barcode reads.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1599, "text": "Barcode sequencing (bar-seq) is a high-throughput, and cost effective method to assay large numbers of cell lineages or genotypes in complex cell pools. Because of its advantages, applications for bar-seq are quickly growing-from using neutral random barcodes to study the evolution of microbes or cancer, to using pseudo-barcodes, such as shRNAs or sgRNAs to simultaneously screen large numbers of cell perturbations. However, the computational pipelines for bar-seq clustering are not well developed. Available methods often yield a high frequency of under-clustering artifacts that result in spurious barcodes, or over-clustering artifacts that group distinct barcodes together. Here, we developed Bartender, an accurate clustering algorithm to detect barcodes and their abundances from raw next-generation sequencing data.Results: In contrast with existing methods that cluster based on sequence similarity alone, Bartender uses a modified two-sample proportion test that also considers cluster size. This modification results in higher accuracy and lower rates of under- and over-clustering artifacts. Additionally, Bartender includes unique molecular identifier handling and a 'multiple time point' mode that matches barcode clusters between different clustering runs for seamless handling of time course data. Bartender is a set of simple-to-use command line tools that can be performed on a laptop at comparable run times to existing methods.Availability and implementation: Bartender is available at no charge for non-commercial use at https://github.com/LaoZZZZZ/bartender-1.1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 837, "text": "Here, we developed Bartender, an accurate clustering algorithm to detect barcodes and their abundances from raw next-generation sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1463, "text": "Bartender is a set of simple-to-use command line tools that can be performed on a laptop at comparable run times to existing methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1602, "text": "Availability and implementation\nBartender is available at no charge for non-commercial use at https://github.com/LaoZZZZZ/bartender-1.1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1329, "text": "Additionally, Bartender includes unique molecular identifier handling and a 'multiple time point' mode that matches barcode clusters between different clustering runs for seamless handling of time course data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1017, "text": "Results\nIn contrast with existing methods that cluster based on sequence similarity alone, Bartender uses a modified two-sample proportion test that also considers cluster size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 1034, "text": "Here, we developed Bartender, an accurate clustering algorithm to detect barcodes and their abundances from raw next-generation sequencing data.
Results: In contrast with existing methods that cluster based on sequence similarity alone, Bartender uses a modified two-sample proportion test that also considers cluster size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1800, "text": "Bartender is a set of simple-to-use command line tools that can be performed on a laptop at comparable run times to existing methods.
Availability and implementation: Bartender is available at no charge for non-commercial use at https://github.com/LaoZZZZZ/bartender-1.1.
Contact: sasha.levy@stonybrook.edu or song.wu@stonybrook.edu.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1346, "text": "Additionally, Bartender includes unique molecular identifier handling and a 'multiple time point' mode that matches barcode clusters between different clustering runs for seamless handling of time course data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 996, "text": "In contrast with existing methods that cluster based on sequence similarity alone, Bartender uses a modified two-sample proportion test that also considers cluster size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 826, "text": "Here, we developed Bartender, an accurate clustering algorithm to detect barcodes and their abundances from raw next-generation sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1442, "text": "Bartender is a set of simple-to-use command line tools that can be performed on a laptop at comparable run times to existing methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069318", "endSection": "abstract" } ] }, { "body": "Which was the first gene therapy to receive marketing authorization in the European Union?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28284702" ], "ideal_answer": [ "The first gene therapy to receive marketing authorization in the European Union was Glybera (alipogene tiparvovec)." ], "exact_answer": [ "Glybera", "Alipogene tiparvovec" ], "type": "factoid", "id": "5c8973f3d558e5f232000007", "snippets": [ { "offsetInBeginSection": 430, "offsetInEndSection": 713, "text": "Alipogene tiparvovec (Glybera\u00ae) is the first gene therapy to receive Marketing Authorization in the European Union; GENIALL (GENetherapy In the MAnagement of Lipoprotein Lipase Deficiency), a 15-year registry focusing on LPLD was launched in 2014 as part of its Risk Management Plan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28284702", "endSection": "abstract" } ] }, { "body": "Is treatment with Bacillus Calmette Guerin used for bladder cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29673806", "http://www.ncbi.nlm.nih.gov/pubmed/11989131", "http://www.ncbi.nlm.nih.gov/pubmed/17945285", "http://www.ncbi.nlm.nih.gov/pubmed/28916862", "http://www.ncbi.nlm.nih.gov/pubmed/19918272", "http://www.ncbi.nlm.nih.gov/pubmed/1732628", "http://www.ncbi.nlm.nih.gov/pubmed/3892051", "http://www.ncbi.nlm.nih.gov/pubmed/3892050", "http://www.ncbi.nlm.nih.gov/pubmed/29362915", "http://www.ncbi.nlm.nih.gov/pubmed/17997439", "http://www.ncbi.nlm.nih.gov/pubmed/21541499", "http://www.ncbi.nlm.nih.gov/pubmed/12031870", "http://www.ncbi.nlm.nih.gov/pubmed/16813873", "http://www.ncbi.nlm.nih.gov/pubmed/2231917", "http://www.ncbi.nlm.nih.gov/pubmed/2359181", "http://www.ncbi.nlm.nih.gov/pubmed/6757467", "http://www.ncbi.nlm.nih.gov/pubmed/19758621", "http://www.ncbi.nlm.nih.gov/pubmed/6381762" ], "ideal_answer": [ "Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5c83f858617e120c34000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28916862", "endSection": "abstract" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1759, "text": "this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28916862", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 313, "text": "response of urothelial precancerous lesions to intravesical BCG treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28916862", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 548, "text": "bladder cancer (BC) is a major clinical issue.METHODS: We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT\u2009+\u2009intravesical instillations of bacillus Calmette-Guerin (BCG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29362915", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 186, "text": "To evaluate the efficacy and safety of a tailored endovesical immunotherapy protocol with biweekly BCG for elderly Patients with high risk non muscle invasive bladder cancer ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29673806", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 137, "text": "Bacillus of Calmette-Guerin (BCG) therapy for high risk non muscle invasive bladder cancer treatment in older patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29673806", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "BCG (Bacillus of Calmette Guerin) has been used for more than 20 years and is currently the most active agent for superficial bladder cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12031870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "BCG (Bacillus of Calmette Guerin) therapy of high-risk superficial bladder cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12031870", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Production of IL-5, a classical T(H)2 cytokine, following bacillus Calmette guerin immunotherapy of bladder cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21541499", "endSection": "title" }, { "offsetInBeginSection": 104, "offsetInEndSection": 200, "text": "Intravesical Bacillus Calmette-Guerin is used to treat patients with superficial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1732628", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 590, "text": "There is some evidence that BCG therapy improves survival and progression rates of patients with high-risk superficial bladder cancer decreasing the proportion who require radical cystectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12031870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Local immunotherapy with bacillus Calmette-Guerin (BCG) is an effective and frequently used treatment for superficial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11989131", "endSection": "abstract" }, { "offsetInBeginSection": 1846, "offsetInEndSection": 2112, "text": "CONCLUSIONS\nIntravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16813873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "PURPOSE\nBacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19758621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "INTRODUCTION\nBacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used to treat urothelial carcinoma since 1976, and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19918272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2231917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3892051", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 352, "text": "We describe a 53 year- old man with a disseminated bacillus Calmette-Guerin (BCG) infection after intravescical instillation for bladder carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11989131", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 683, "text": "We tested the hypothesis that tumor expression of natural cytotoxicity receptor ligands can serve as a predictive factor for the response to intravesical bacillus Calmette-Guerin in patients with nonmuscle invasive, high grade bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17945285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3892050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 446, "text": "Pancreatic and psoas abscesses as a late complication of intravesical administration of bacillus Calmette-Guerin for bladder cancer: a case report and review of the literature.This case illustrates the fact that although intravesical administration of bacillus Calmette-Guerin is generally considered to be safe, it is not exempt from complications and these could appear immediately after treatment or as a delayed complication many years later.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19918272", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Effects of local bacillus Calmette-Guerin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall.The antitumoral effects of intravesical bacillus Calmette-Guerin against recurrent superficial urothelial bladder cancer seem to be linked to immunological effector mechanisms. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2359181", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer.Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2231917", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results.We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3892051", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Bacillus Calmette-Guerin immunotherapy for bladder cancer.Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3892050", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients.Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16813873", "endSection": "title" }, { "offsetInBeginSection": 2120, "offsetInEndSection": 2425, "text": "Our results suggest that intralesional bacillus Calmette-Guerin immunotherapy can afford long term protection from transplanted bladder cancer, and that live bacillus Calmette-Guerin is superior to levamisole and P3 + Re-glycolipid + bacillus Calmette-Guerin cell walls in the treatment of bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6381762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6757467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Up to 90% of patients with high grade superficial bladder tumors experience tumor recurrence and up to 50% have progression despite bacillus Calmette-Guerin treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17945285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "We review how the bacillus Calmette-Guerin vaccine evolved to become standard therapy for superficial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17997439", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 332, "text": "We reviewed the historical literature describing the origin of the bacillus Calmette-Guerin vaccine as an anticancer agent and its singular success as the most effective immunotherapy used against a human neoplasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17997439", "endSection": "abstract" } ] }, { "body": "List lymphocytes that are analyzed by a flow cytometer.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29516957", "http://www.ncbi.nlm.nih.gov/pubmed/29935030", "http://www.ncbi.nlm.nih.gov/pubmed/29466232" ], "ideal_answer": [ "Quantitation of lymphocyte subsets (B cells, T cells, CD4 and CD8 T cells and NK cells) classically relies on quantitation of lymphocytes and immunophenotyping by flow cytometry." ], "exact_answer": [ [ "B cells" ], [ "T cells" ], [ "CD4 and CD8 T cells" ], [ "NK cells" ] ], "type": "list", "id": "5c5f0f581a4c55d80b000012", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 191, "text": " Quantitation of lymphocyte subsets (B cells, T cells, CD4 and CD8 T cells and NK cells) classically relies on quantitation of lymphocytes and immunophenotyping by flow cytometry. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29466232", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 653, "text": "The distributions of Th17 cells, regulatory Treg-cells, CD4+ T-cells, CD8+ T-cells, and CD3+ T-cells were determined by flow cytometer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29516957", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 80, "text": " main lymphocyte subsets (T, B and NK cell ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29935030", "endSection": "abstract" } ] }, { "body": "List two drugs that are included in the Akynzeo pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25516691", "http://www.ncbi.nlm.nih.gov/pubmed/26613606", "http://www.ncbi.nlm.nih.gov/pubmed/29547597", "http://www.ncbi.nlm.nih.gov/pubmed/27473611" ], "ideal_answer": [ "Akynzeo is an oral fixed combination of netupitant and palonosetron that is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV)." ], "exact_answer": [ [ "netupitant" ], [ "palonosetron" ] ], "type": "list", "id": "5c73ad057c78d6947100008f", "snippets": [ { "offsetInBeginSection": 268, "offsetInEndSection": 533, "text": "OBJECTIVES: To review the latest antiemetic guideline recommendations and provide an update on the use of NEPA, a fixed combination antiemetic composed of the neurokinin-1 receptor antagonist (RA) netupitant and the 5-hydroxytryptamine-3 RA palonosetron (Akynzeo\u00ae).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547597", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1026, "text": "An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo(\u00ae)) with >85% antiemetic efficacy is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27473611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo(\u00ae)) is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26613606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Ledipasvir/sofosbuvir (Harvoni) for hepatitis C virus genotype 1 infection; dulaglutide (Trulicity) for glycemic control in type-2 diabetes; netupitant/palonosetron (Akynzeo) for prevention of nausea and vomiting related to chemotherapy; and naloxegol (Movantik) for opioid-induced constipation in patients with chronic noncancer pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Netupitant/Palonosetron: A Review in the Prevention of Chemotherapy-Induced Nausea and Vomiting.An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo(\u00ae)) is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26613606", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Pharmaceutical approval update.Ledipasvir/sofosbuvir (Harvoni) for hepatitis C virus genotype 1 infection; dulaglutide (Trulicity) for glycemic control in type-2 diabetes; netupitant/palonosetron (Akynzeo) for prevention of nausea and vomiting related to chemotherapy; and naloxegol (Movantik) for opioid-induced constipation in patients with chronic noncancer pain. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516691", "endSection": "title" } ] }, { "body": "Describe CapSim", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29092025" ], "ideal_answer": [ "CapSim is a software package for simulation of targeted capture sequencing. Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridization and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms. The simulated data can be used for evaluating the performance of the analysis pipeline, as well as the efficiency of the probe design. Parameters of the various stages in the sequencing process can also be evaluated in order to optimize the experiments.Availability and implementation: CapSim is publicly available under BSD license at https://github.com/Devika1/capsim." ], "type": "summary", "id": "5c65b2e87c78d6947100000b", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 1137, "text": "Targeted sequencing using capture probes has become increasingly popular in clinical applications due to its scalability and cost-effectiveness. The approach also allows for higher sequencing coverage of the targeted regions resulting in better analysis statistical power. However, because of the dynamics of the hybridization process, it is difficult to evaluate the efficiency of the probe design prior to the experiments which are time consuming and costly.Results: We developed CapSim, a software package for simulation of targeted sequencing. Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridization and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms. The simulated data can be used for evaluating the performance of the analysis pipeline, as well as the efficiency of the probe design. Parameters of the various stages in the sequencing process can also be evaluated in order to optimize the experiments.Availability and implementation: CapSim is publicly available under BSD license at https://github.com/Devika1/capsim.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Simulating the dynamics of targeted capture sequencing with CapSim.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "title" }, { "offsetInBeginSection": 561, "offsetInEndSection": 767, "text": "Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridization and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 560, "text": "Results\nWe developed CapSim, a software package for simulation of targeted sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 784, "text": "Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridization and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" }, { "offsetInBeginSection": 920, "offsetInEndSection": 1307, "text": "Parameters of the various stages in the sequencing process can also be evaluated in order to optimize the experiments.
Availability and implementation: CapSim is publicly available under BSD license at https://github.com/Devika1/capsim.
Contact: l.coin@imb.uq.edu.au.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 577, "text": "However, because of the dynamics of the hybridization process, it is difficult to evaluate the efficiency of the probe design prior to the experiments which are time consuming and costly.
Results: We developed CapSim, a software package for simulation of targeted sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 539, "text": "We developed CapSim, a software package for simulation of targeted sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 746, "text": "Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridization and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29092025", "endSection": "abstract" } ] }, { "body": "Which company produces Glybera?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27762892" ], "ideal_answer": [ "Glybera is a product of Chiesi Pharma." ], "exact_answer": [ "Chiesi Pharma" ], "type": "factoid", "id": "5c8974bcd558e5f232000008", "snippets": [ { "offsetInBeginSection": 329, "offsetInEndSection": 719, "text": "Interestingly, the RM development cycle seems to obey the Gartner hype cycle, now at the enlightenment phase, after past exaggerated expectations and discouragements, as suggested by increasing numbers of clinical trials and recent market approvals of RM solutions in both Europe (Glybera and Holoclar\u00ae from Chiesi Pharma and Strimvelis\u00ae from GSK) and Japan (Remestemcel-L from Mesoblast\u00ae).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27762892", "endSection": "abstract" } ] }, { "body": "What is the mode of action of Tetrocarcin-A?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15667975", "http://www.ncbi.nlm.nih.gov/pubmed/30312728", "http://www.ncbi.nlm.nih.gov/pubmed/12560233", "http://www.ncbi.nlm.nih.gov/pubmed/17350598" ], "ideal_answer": [ "The anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast cancer cells." ], "type": "summary", "id": "5c84394375a4a5d219000003", "snippets": [ { "offsetInBeginSection": 233, "offsetInEndSection": 378, "text": "Tetrocarcin A (TC-A) and bcl-2 antisense oligonucleotides exhibit antitumor activity by inhibiting Bcl-2 function and transcription, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15667975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350598", "endSection": "title" }, { "offsetInBeginSection": 329, "offsetInEndSection": 444, "text": "Here we find that an anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350598", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Tetrocarcin-A (TC-A), an antibiotic agent isolated from actinomycetes, has recently been described to antagonize Bcl-2 functions, thereby sensitizing tumor cells to cell death signals under control of Bcl-2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12560233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Natural compound Tetrocarcin-A downregulates Junctional Adhesion Molecule-A in conjunction with HER2 and inhibitor of apoptosis proteins and inhibits tumor cell growth.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312728", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Tetrocarcin-A (TC-A), an antibiotic agent isolated from actinomycetes, has recently been described to antagonize Bcl-2 functions, thereby sensitizing tumor cells to cell death signals under control of Bcl-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12560233", "endSection": "abstract" } ] }, { "body": "List some substances important for proper nervous system function that gut microbes produce.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27571098", "http://www.ncbi.nlm.nih.gov/pubmed/29748506", "http://www.ncbi.nlm.nih.gov/pubmed/26598580" ], "ideal_answer": [ "serotonin\ngamma-aminobutyric acid\nshort-chain fatty acids\nneurotransmitters" ], "exact_answer": [ [ "serotonin" ], [ "gamma-aminobutyric acid" ], [ "short-chain fatty acids" ], [ "neurotransmitters" ] ], "type": "list", "id": "5c5f2dc21a4c55d80b000024", "snippets": [ { "offsetInBeginSection": 700, "offsetInEndSection": 862, "text": " Gut microorganisms are capable of producing and delivering neuroactive substances such as serotonin and gamma-aminobutyric acid, which act on the gut-brain axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598580", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 473, "text": "Prebiotic compounds are appealing for this purpose as they are generally food-grade substances only degraded by microbes, such as bifidobacteria and lactobacilli, from which beneficial short-chain fatty acids are produced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571098", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1077, "text": "Moreover, gut microbiota are considerable sources of NTs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29748506", "endSection": "abstract" } ] }, { "body": "Safinamide is approved for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29760163", "http://www.ncbi.nlm.nih.gov/pubmed/29670409", "http://www.ncbi.nlm.nih.gov/pubmed/28110399", "http://www.ncbi.nlm.nih.gov/pubmed/30271159", "http://www.ncbi.nlm.nih.gov/pubmed/30142650", "http://www.ncbi.nlm.nih.gov/pubmed/27802242", "http://www.ncbi.nlm.nih.gov/pubmed/30291173", "http://www.ncbi.nlm.nih.gov/pubmed/29441484", "http://www.ncbi.nlm.nih.gov/pubmed/29167350", "http://www.ncbi.nlm.nih.gov/pubmed/25851099", "http://www.ncbi.nlm.nih.gov/pubmed/29339106", "http://www.ncbi.nlm.nih.gov/pubmed/26587996" ], "ideal_answer": [ "Safinamide is a monoamine-oxidase B (MAO-B) inhibitor licensed as add-on therapy for people with idiopathic Parkinson's disease who are experiencing motor fluctuations with levodopa." ], "exact_answer": [ "Parkinson's disease" ], "type": "factoid", "id": "5c73ad077c78d69471000090", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Safinamide has been recently approved as an add-on to levodopa therapy for Parkinson disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167350", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1773, "text": " These data are consistent with the anticonvulsant and antiparkinsonian actions of safinamide and provide support for the nondopaminergic mechanism of its action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Safinamide: a new hope for Parkinson's disease?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29339106", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 483, "text": "The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson's disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29339106", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1054, "text": "Overall, safinamide can be considered to have potential antidyskinetic and neuroprotective effects and future trials and/or studies should be performed to provide further evidence for its potential as an anti-PD drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29339106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Real life evaluation of safinamide effectiveness in Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29441484", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "In this retrospective study, we evaluated both efficacy and effectiveness of safinamide 50 and 100\u00a0mg in the treatment of motor fluctuations and disabling dyskinesias in a cohort of patients with idiopathic Parkinson's disease (PD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29441484", "endSection": "abstract" }, { "offsetInBeginSection": 1451, "offsetInEndSection": 1620, "text": "In conclusion, safinamide is safe and effective in improving motor complications in patients with idiopathic PD and can be considered a useful levodopa sparing strategy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29441484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Safinamide: an add-on treatment for managing Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670409", "endSection": "title" }, { "offsetInBeginSection": 2, "offsetInEndSection": 208, "text": "Safinamide (Xadago - Zambon S.p.A) is a monoamine-oxidase B (MAO-B) inhibitor licensed as add-on therapy for people with idiopathic Parkinson's disease who are experiencing motor fluctuations with levodopa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29760163", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 374, "text": "In the EU, safinamide is approved for the treatment of mid- to late-stage fluctuating Parkinson's disease (PD) as add-on therapy to a stable dose of levodopa alone or in combination with other PD medications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28110399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "AIM\nSafinamide (Xadago\u00ae) is a newly approved selective MAO-B inhibitor for the treatment of Parkinson's Disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142650", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 288, "text": "Safinamide is a\u00a0new drug with dopaminergic and non-dopaminergic properties, approved in Europe as adjunct therapy to levodopa for the treatment of fluctuating PD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27802242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Safinamide (Xadago\u00ae) is a novel medication with both dopaminergic and non-dopaminergic effects, approved first by the European Commission and more recently by the US Food and Drug Administration (FDA) as an adjunctive treatment to carbidopa/levodopa in patients with mid- to late-stage Parkinson's disease (PD) and motor fluctuations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30271159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Safinamide (Xadago) is a novel dual-mechanism drug that has been approved in the European Union and United States as add-on treatment to levodopa in Parkinson's disease therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30291173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Safinamide has been recently approved as an add-on to levodopa therapy for Parkinson disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167350", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 705, "text": "Safinamide is approved in the EU, Iceland, Lichtenstein and Norway, as an add-on therapy to stable-dose levodopa, alone or in combination with other PD therapies in mid- to late-stage fluctuating PD patients; regulatory submissions have also been filed in the USA and Switzerland for its use in this indication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25851099", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 598, "text": "In 2014, safinamide was approved in the European Economic Area, as \"an add-on therapy to stable dose levodopa, alone or in combination with other PD therapies in mid- to late-stage-fluctuating PD patients.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26587996", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 399, "text": "In the EU, safinamide is approved for the treatment of mid- to late-stage fluctuating Parkinson's disease (PD) as add-on therapy to a stable dose of levodopa alone or in combination with other PD medications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28110399", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 451, "text": "is a novel medication with both dopaminergic and non-dopaminergic effects, approved first by the European Commission and more recently by the US Food and Drug Administration (FDA) as an adjunctive treatment to carbidopa/levodopa in patients with mid- to late-stage Parkinson's disease (PD) and motor fluctuations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30271159", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 596, "text": "In 2014, safinamide was approved in the European Economic Area, as an add-on therapy to stable dose levodopa, alone or in combination with other PD therapies in mid- to late-stage-fluctuating PD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26587996", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 277, "text": "Safinamide is a\u00a0new drug with dopaminergic and non-dopaminergic properties, approved in Europe as adjunct therapy to levodopa for the treatment of fluctuating PD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27802242", "endSection": "abstract" } ] }, { "body": "What is the tradename of apixaban?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23677804" ], "ideal_answer": [ "The tradename of apixaban is Eliquis." ], "exact_answer": [ "Eliquis" ], "type": "factoid", "id": "5c920fc3ecadf2e73f000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The direct factor Xa inhibitor apixaban (Eliquis(\u00ae)) has predictable pharmacodynamics and pharmacokinetics and does not require routine anticoagulation monitoring. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23677804", "endSection": "abstract" } ] }, { "body": "Under which environment does SELANSI run?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29040384" ], "ideal_answer": [ "SELANSI (SEmi-LAgrangian SImulation of GRNs) is a software toolbox for the simulation of stochastic multidimensional gene regulatory networks. SELANSI exploits intrinsic structural properties of gene regulatory networks to accurately approximate the corresponding Chemical Master Equation with a partial integral differential equation that is solved by a semi-lagrangian method with high efficiency. SELANSI runs under the MATLAB environment, and is available under GPLv3 license at https://sites.google.com/view/selansi.", "matlab environment" ], "exact_answer": [ "MATLAB" ], "type": "factoid", "id": "5c6ab4c17c78d6947100001d", "snippets": [ { "offsetInBeginSection": 525, "offsetInEndSection": 1467, "text": "This work presents SELANSI (SEmi-LAgrangian SImulation of GRNs), a software toolbox for the simulation of stochastic multidimensional gene regulatory networks. SELANSI exploits intrinsic structural properties of gene regulatory networks to accurately approximate the corresponding Chemical Master Equation with a partial integral differential equation that is solved by a semi-lagrangian method with high efficiency. Networks under consideration might involve multiple genes with self and cross regulations, in which genes can be regulated by different transcription factors. Moreover, the validity of the method is not restricted to a particular type of kinetics. The tool offers total flexibility regarding network topology, kinetics and parameterization, as well as simulation options.Availability and implementation: SELANSI runs under the MATLAB environment, and is available under GPLv3 license at https://sites.google.com/view/selansi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040384", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1470, "text": "Availability and implementation\nSELANSI runs under the MATLAB environment, and is available under GPLv3 license at https://sites.google.com/view/selansi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040384", "endSection": "abstract" }, { "offsetInBeginSection": 1208, "offsetInEndSection": 1540, "text": "The tool offers total flexibility regarding network topology, kinetics and parameterization, as well as simulation options.
Availability and implementation: SELANSI runs under the MATLAB environment, and is available under GPLv3 license at https://sites.google.com/view/selansi.
Contact: antonio@iim.csic.es.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040384", "endSection": "abstract" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1415, "text": "SELANSI runs under the MATLAB environment, and is available under GPLv3 license at https://sites.google.com/view/selansi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040384", "endSection": "abstract" } ] }, { "body": "Is eculizumab used for treatment of myasthenia gravis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28010051", "http://www.ncbi.nlm.nih.gov/pubmed/29337452", "http://www.ncbi.nlm.nih.gov/pubmed/23512355", "http://www.ncbi.nlm.nih.gov/pubmed/29266249", "http://www.ncbi.nlm.nih.gov/pubmed/23945282", "http://www.ncbi.nlm.nih.gov/pubmed/29435915", "http://www.ncbi.nlm.nih.gov/pubmed/29655452", "http://www.ncbi.nlm.nih.gov/pubmed/29066163" ], "ideal_answer": [ "Yes, eculizumab is used for treatment of myasthenia gravis." ], "exact_answer": "yes", "type": "yesno", "id": "5c73acf17c78d69471000089", "snippets": [ { "offsetInBeginSection": 1198, "offsetInEndSection": 1313, "text": "Eculizumab treatment improved symptoms compared with placebo in a phase II study in patients with refractory gMG. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29266249", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 251, "text": "Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29337452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "The humanized monoclonal antibody eculizumab (Soliris\u00ae) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29435915", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1623, "text": "Although several questions remain, such as duration of treatment, cost effectiveness and long-term efficacy and tolerability, current evidence indicates that eculizumab is a valuable emerging therapy for patients with refractory gMG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29435915", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 542, "text": "The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29655452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "INTRODUCTION\nA phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28010051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "QMG and MG-ADL correlations: Study of eculizumab treatment of myasthenia gravis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28010051", "endSection": "title" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1025, "text": "Rituximab seems to be particularly effective in MuSK myasthenia gravis, and eculizumab arises as an option in refractory AChR myasthenia gravis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945282", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 388, "text": "Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29066163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29066163", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "The humanized monoclonal antibody eculizumab (Soliris\u00ae) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29435915", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 250, "text": "Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29337452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Eculizumab: A Review in Generalized Myasthenia Gravis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29435915", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512355", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Eculizumab: A Review in Generalized Myasthenia Gravis.) ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29435915", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "INTRODUCTION: A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28010051", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 548, "text": "Correlations were then analyzed between these assessments.
METHODS: Patients were given eculizumab or placebo during the first 16-week treatment period of the crossover study, with treatment assignments reversed for the second treatment period following a 5-week washout.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28010051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28010051", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 540, "text": "The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29655452", "endSection": "abstract" } ] }, { "body": "What is the name of the Cas13 based diagnostic test for the Zika and dengue viruses?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29700266" ], "ideal_answer": [ "The Cas13-based platform that can detect Zika and dengue viruses is called SHERLOCK (specific high-sensitivity enzymatic reporter unlocking)." ], "exact_answer": [ "SHERLOCK (specific high-sensitivity enzymatic reporter unlocking)" ], "type": "factoid", "id": "5c92871decadf2e73f000016", "snippets": [ { "offsetInBeginSection": 123, "offsetInEndSection": 371, "text": "In this study, we demonstrate that the Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform can detect Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29700266", "endSection": "abstract" } ] }, { "body": "What are CRISPR-Cas12a proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29449511" ], "ideal_answer": [ "CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing on the basis of its ability to generate targeted, double-stranded DNA breaks. RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules" ], "type": "summary", "id": "5c8feae70101eac87000000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29449511", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 431, "text": "CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing on the basis of its ability to generate targeted, double-stranded DNA breaks. Here we show that RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29449511", "endSection": "abstract" } ] }, { "body": "What type of drug is apixaban?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27653758" ], "ideal_answer": [ "Apixaban is an anticoagulant." ], "exact_answer": [ "anticoagulant" ], "type": "factoid", "id": "5c920f13ecadf2e73f000010", "snippets": [ { "offsetInBeginSection": 160, "offsetInEndSection": 325, "text": "Like other direct oral anticoagulants (DOACs), apixaban has generally predictable pharmacological properties and does not require routine anticoagulation monitoring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27653758", "endSection": "abstract" } ] }, { "body": "Can cardiospheres be produced from skin fibroblasts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29999590" ], "ideal_answer": [ "Yes, induced cardiospheres (iCS) can be produced by somatic reprogramming of mouse fibroblasts using a panel of pluripotent transcription factors and cardiotrophic growth factors." ], "exact_answer": "yes", "type": "yesno", "id": "5c928afeecadf2e73f000018", "snippets": [ { "offsetInBeginSection": 331, "offsetInEndSection": 461, "text": "Therefore, there is an emerging interest in generating cardiosphere-like stem cells from somatic cells via somatic reprogramming. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29999590", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 805, "text": "Here we provide the detailed protocol for generating induced cardiospheres (iCS) for cardiac regeneration by somatic reprogramming of mouse fibroblasts using a panel of pluripotent transcription factors and cardiotrophic growth factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29999590", "endSection": "abstract" } ] }, { "body": "What the chromsomal location of the gene that is deleted in Potocki-Shaffer syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23239541", "http://www.ncbi.nlm.nih.gov/pubmed/15852040", "http://www.ncbi.nlm.nih.gov/pubmed/28571721", "http://www.ncbi.nlm.nih.gov/pubmed/19222835", "http://www.ncbi.nlm.nih.gov/pubmed/28127865", "http://www.ncbi.nlm.nih.gov/pubmed/15666301", "http://www.ncbi.nlm.nih.gov/pubmed/20140962", "http://www.ncbi.nlm.nih.gov/pubmed/26333423", "http://www.ncbi.nlm.nih.gov/pubmed/22822387", "http://www.ncbi.nlm.nih.gov/pubmed/25653495" ], "ideal_answer": [ "In Potocki-Shaffer syndrome (PSS), the full phenotypic spectrum is manifested when deletions are at least 2.1\u2009Mb in size at 11p11.2", "Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome caused by heterozygous deletion of 11p11.2p12." ], "exact_answer": [ "11p11.2p12" ], "type": "factoid", "id": "5c72b7277c78d69471000073", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "In Potocki-Shaffer syndrome (PSS), the full phenotypic spectrum is manifested when deletions are at least 2.1\u2009Mb in size at 11p11.2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26333423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)]. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15852040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki-Shaffer syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15852040", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Potocki-Shaffer syndrome is a rare contiguous gene deletion syndrome due to haploinsufficiency of the 11p11.2p12 region and is characterized by craniofacial abnormalities, developmental delay, intellectual disability, multiple exostoses, and biparietal foramina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20140962", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 710, "text": "This is also the first report describing deletion of 11p11.12-p11.2 and neocentromere formation resulting in inherited Potocki-Shaffer syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15666301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15852040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Potocki-Shaffer Syndrome is a rare neurodevelopmental syndrome associated with microdeletion of a region of Chromosome 11p11.2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28571721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Potocki-Shaffer syndrome is a contiguous gene deletion syndrome involving 11p11.2p12 and characterized by multiple exostoses, biparietal foramina, genitourinary anomalies in males, central nervous system abnormalities, intellectual disability, and craniofacial abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28127865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Interstitial deletion 11(p11.12p11.2) and analphoid marker formation results in inherited Potocki-Shaffer syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15666301", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Potocki-Shaffer syndrome (PSS) is a rare disorder caused by haploinsufficiency of genes located on the proximal short arm of chromosome 11 (11p11.2p12).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23239541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki-Shaffer syndrome.Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)]. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15852040", "endSection": "title" }, { "offsetInBeginSection": 609, "offsetInEndSection": 785, "text": "The deletion (11p13-p12) located in the area between the deletions associated with the WAGR and Potocki-Shaffer syndromes had a maximum size of 8.5 Mb and encompasses 44 genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19222835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Delayed Diagnosis of Potocki-Shaffer Syndrome in a Woman with Multiple Exostoses and Mental Retardation.We describe the case of an adult patient affected by multiple exostoses, severe mental retardation, epilepsy and facial dysmorphisms with a deletion of \u223c2.3 Mb on chromosome 11p11.21, correlated to Potocki-Shaffer syndrome (PSS). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22822387", "endSection": "title" }, { "offsetInBeginSection": 566, "offsetInEndSection": 714, "text": "This is also the first report describing deletion of 11p11.12-p11.2 and neocentromere formation resulting in inherited Potocki-Shaffer syndrome.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15666301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": " WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities and mental retardation) and Potocki-Shaffer syndrome are rare contiguous gene deletion syndromes caused by deletions of the 11p14-p12 chromosome region.We present a patient with mental retardation, unilateral cataract, bilateral ptosis, genital abnormalities, seizures and a dysmorphic face.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19222835", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 643, "text": "The deletion (11p13-p12) located in the area between the deletions associated with the WAGR and Potocki-Shaffer syndromes had a maximum size of 8.5 Mb and encompasses 44 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19222835", "endSection": "abstract" } ] }, { "body": "List 3 enterotoxins produced by Clostridium difficile.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28366569", "http://www.ncbi.nlm.nih.gov/pubmed/28707191", "http://www.ncbi.nlm.nih.gov/pubmed/28232034", "http://www.ncbi.nlm.nih.gov/pubmed/12825250", "http://www.ncbi.nlm.nih.gov/pubmed/2115017" ], "ideal_answer": [ "Toxin A (TcdA), toxin B (TcdB), and binary toxin (CDT) produced by Clostridium difficile (CD)" ], "exact_answer": [ [ "binary toxin (CDT" ], [ "Toxin A (TcdA)" ], [ "Toxin B (TcdB)" ] ], "type": "list", "id": "5c851a8175a4a5d219000005", "snippets": [ { "offsetInBeginSection": 420, "offsetInEndSection": 653, "text": "The toxins produced by the C. diff. (toxin A, toxin B, and binary toxin) are the agents that cause injury and disease. Only toxin producing C. diff. Strains will cause disease. Binary toxin by itself is not thought to produce disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28707191", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 745, "text": "Binary toxin causes disease in humans when present with toxin A and B producing bacteria, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28707191", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 387, "text": " The main virulence factor is related to the release of two major exotoxins, toxin A (TcdA) and toxin B (TcdB). Recent C. difficile-associated disease (CDAD) outbreaks have been caused by hypervirulent strains which secrete an additional binary toxin (CDTa/CDTb). V", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The exotoxins toxin A (TcdA) and toxin B (TcdB) are produced by the bacterial pathogen Clostridium difficile and are responsible for the pathology associated with C. difficile infection (CDI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28232034", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 448, "text": "The pathogenic organism, Clostridium difficile, produces two enterotoxins, toxin A and toxin B, that cause colonic mucosal inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12825250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Enterotoxins from Clostridium difficile; diarrhoeogenic potency and morphological effects in the rat intestine.The action of toxins A, B, and C from Clostridium difficile was studied in the small intestine and colon of rats. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2115017", "endSection": "title" } ] }, { "body": "Which tissue secretes vaspin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28756250", "http://www.ncbi.nlm.nih.gov/pubmed/29734265" ], "ideal_answer": [ "Visceral adipose tissue-derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions." ], "exact_answer": [ "Adipose Tissue" ], "type": "factoid", "id": "5c7d5ae9d774d04240000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Vaspin expression is increased in white adipose tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28756250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Visceral adipose tissue-derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29734265", "endSection": "abstract" } ] }, { "body": "List adipokines.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27629594", "http://www.ncbi.nlm.nih.gov/pubmed/28877872", "http://www.ncbi.nlm.nih.gov/pubmed/28857629", "http://www.ncbi.nlm.nih.gov/pubmed/28393393" ], "ideal_answer": [ "adiponectin\nleptin\nresistin" ], "exact_answer": [ [ "adiponectin" ], [ "leptin" ], [ "resistin" ] ], "type": "list", "id": "5c7d520ed774d0424000000f", "snippets": [ { "offsetInBeginSection": 656, "offsetInEndSection": 691, "text": "adipokines (adiponectin and leptin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27629594", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 117, "text": " number of adipokines, like Resistin (RETN)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28393393", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 680, "text": "Plasma adipokine levels were measured before exercise, and at 5 and 90\u2009min after exercise on the first and the last training days. Adiponectin was higher at 5\u2009min than 90\u2009min post-exercise (11.7\u2009\u00b1\u20097.3 and 10.5\u2009\u00b1\u20095.8\u2009ng/ml; p\u2009=\u2009.01) in the first exercise day. Leptin decreased 5\u2009min after exercise (23.6\u2009\u00b1\u200913.2 vs. baseline 27.8\u2009\u00b1\u200914.4\u2009ng/ml; p\u2009<\u2009.01) and remained depressed following 90\u2009min (p\u2009<\u2009.01)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28857629", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 52, "text": " leptin, adiponectin, resistin, ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28877872", "endSection": "title" } ] }, { "body": "List features of the DOOR syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12457410", "http://www.ncbi.nlm.nih.gov/pubmed/7808978", "http://www.ncbi.nlm.nih.gov/pubmed/8256819", "http://www.ncbi.nlm.nih.gov/pubmed/15279406", "http://www.ncbi.nlm.nih.gov/pubmed/19830001", "http://www.ncbi.nlm.nih.gov/pubmed/18263975", "http://www.ncbi.nlm.nih.gov/pubmed/21743113", "http://www.ncbi.nlm.nih.gov/pubmed/17994565" ], "ideal_answer": [ "DOOR syndrome is a rare multisystem genetic disorder, consisting of deafness (sensorineural), onychodystrophy, osteodystrophy, and mental retardation." ], "exact_answer": [ [ "deafness" ], [ "onychodystrophy" ], [ "osteodystrophy" ], [ "mental retardation" ] ], "type": "list", "id": "5c73ace67c78d69471000083", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "DOOR syndrome is a rare multisystem genetic disorder, consisting of deafness (sensorineural), onychodystrophy, osteodystrophy, and mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21743113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "We report the anaesthetic management of a 48-year-old male patient with Deafness, Onycho-Osteodystrophy and mental Retardation syndrome, epilepsy and cerebral palsy who had two dental procedures under anaesthetic care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19830001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "We present the case of a 9-year-old boy with DOOR syndrome recognized in the first year of his life because of a delayed development of speech. The diagnosis was based on characteristic abnormalities, including congenital deafness, nail and bone abnormalities, and mild mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18263975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "DOOR syndrome (deafness, onychodystrophy, osteodystrophy, and mental retardation) is a rarely described disorder with less than 35 reports in the literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17994565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "[DOOR (deafness, onychodystrophy, osteodystrophy, mental retardation) syndrome].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15279406", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "DOOR syndrome (deafness, onychodystrophy, osteodystrophy, and mental retardation) is a rarely described disorder with less than 35 reports in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17994565", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 388, "text": "The hallmarks of the syndrome, represented in the DOOR acronym, include sensorineural hearing loss, hypoplastic or absent nails on the hands and feet, small or absent distal phalanges of the hands and feet, and mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17994565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Four patients from three families with the clinical features of DOOR syndrome (onycho-osteodystrophy, dystrophic thumbs, sensorineural deafness, and increased urinary levels of 2-oxoglutarate) are the subjects of this report.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12457410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The acronym DOOR was first used by Cantwell in 1975 to describe a syndrome comprising sensorineural deafness, osteodystrophy, onychodystrophy, and mental retardation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7808978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "DOOR syndrome (deafness, onycho-osteodystrophy, and mental retardation): a new patient and delineation of neurologic variability among recessive cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8256819", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Congenital heart disease and urinary tract abnormalities in two siblings with DOOR syndrome.The acronym DOOR was first used by Cantwell in 1975 to describe a syndrome comprising sensorineural deafness, osteodystrophy, onychodystrophy, and mental retardation. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7808978", "endSection": "title" } ] }, { "body": "Which web-based pedigree editors are available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29095980", "http://www.ncbi.nlm.nih.gov/pubmed/17488757" ], "ideal_answer": [ "Pedigreejs and Madeline 2.0 Pedigree Drawing Engine (PDE)" ], "exact_answer": [ [ "Pedigreejs" ], [ "Madeline 2.0 Pedigree Drawing Engine (PDE)" ] ], "type": "list", "id": "5c6d6b377c78d69471000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "pedigreejs: a web-based graphical pedigree editor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29095980", "endSection": "title" }, { "offsetInBeginSection": 321, "offsetInEndSection": 1092, "text": "Several standalone graphical pedigree editors and drawing applications exist but there are no freely available lightweight graphical pedigree editors that can be easily configured and incorporated into web applications.Results: We developed 'pedigreejs', an interactive graphical pedigree editor written in JavaScript, which uses standard pedigree nomenclature. Pedigreejs provides an easily configurable, extensible and lightweight pedigree editor. It makes use of an open-source Javascript library to define a hierarchical layout and to produce images in scalable vector graphics (SVG) format that can be viewed and edited in web browsers.Availability and implementation: The software is freely available under GPL licence (https://ccge-boadicea.github.io/pedigreejs/).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29095980", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Madeline 2.0 PDE: a new program for local and web-based pedigree drawing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17488757", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 962, "text": "The Madeline 2.0 Pedigree Drawing Engine (PDE) is a pedigree drawing program for use in linkage and family-based association studies. The program is designed to handle large and complex pedigrees with an emphasis on readability and aesthetics. For complex pedigrees, we use a hybrid algorithm in which consanguinous loops are drawn as cyclic graphs whenever possible, but we resort to acyclic graphs when matings can no longer be connected without line crossings. A similar hybrid approach is used to avoid line crossings for matings between distant descendants of different founding groups. Written in object-oriented C++ and released under the GNU General Public License (GPL), Madeline 2.0 PDE reads input files specified on the command line and generates pedigree drawings without user interaction. Pedigree output in scalable vector graphics (SVG) format can be viewed in browsers with native SVG rendering support or in vector graphics editors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17488757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Madeline 2.0 PDE: a new program for local and web-based pedigree drawing.http://kellogg.umich.edu/madeline.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17488757", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "pedigreejs: a web-based graphical pedigree editor.Supplementary data are available at Bioinformatics online.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29095980", "endSection": "title" } ] }, { "body": "What is the mechanism of action of Solriamfetol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30365900", "http://www.ncbi.nlm.nih.gov/pubmed/30269642", "http://www.ncbi.nlm.nih.gov/pubmed/30521757", "http://www.ncbi.nlm.nih.gov/pubmed/29891587" ], "ideal_answer": [ "Solriamfetol is a selective norepinephrine-dopamine reuptake inhibitor. It is used to treat excessive sleepiness in obstructive sleep apnea and narcolepsy patients." ], "type": "summary", "id": "5c73ad097c78d69471000092", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891587", "endSection": "title" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1605, "text": "The dual activity of solriamfetol at DA and NE transporters and the lack of significant monoamine-releasing properties of solriamfetol might explain the differences in the in vivo effects of solriamfetol compared with modafinil or amphetamine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "BACKGROUND:: This study evaluated the human abuse potential of solriamfetol (formerly JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "A randomized, double-blind, placebo-controlled, crossover study to evaluate the human abuse liability of solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269642", "endSection": "title" }, { "offsetInBeginSection": 239, "offsetInEndSection": 485, "text": " A new drug, solriamfetol, a selective norepinephrine-dopamine reuptake inhibitor, is the first drug of its class that is being considered by the US Food and Drug Administration (FDA) to treat excessive sleepiness in OSA and narcolepsy patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30365900", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 623, "text": "OBJECTIVES: To evaluate the efficacy and safety of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects, for the treatment of excessive sleepiness in participants with obstructive sleep apnea with current or prior sleep apnea treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30521757", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1361, "text": "Moreover, the wake-promoting effects of solriamfetol are probably owing to activity at DA and NE transporters rather than other neurotransmitter systems, such as histamine or orexin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891587", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 1084, "text": "Results indicate that solriamfetol has dual reuptake inhibition activity at dopamine (DA; IC50 = 2.9 \u03bcM) and norepinephrine (NE; IC50 = 4.4 \u03bcM) transporters, and this activity is associated in vivo with increased extracellular concentration of DA and NE as measured by microdialysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891587", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 470, "text": "A new drug, solriamfetol, a selective norepinephrine-dopamine reuptake inhibitor, is the first drug of its class that is being considered by the US Food and Drug Administration (FDA) to treat excessive sleepiness in OSA and narcolepsy patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30365900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND:\nThis study evaluated the human abuse potential of solriamfetol (formerly JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269642", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 550, "text": "A new drug, solriamfetol, a selective norepinephrine-dopamine reuptake inhibitor, is the first drug of its class that is being considered by the US Food and Drug Administration (FDA) to treat excessive sleepiness in OSA and narcolepsy patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30365900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "A randomized, double-blind, placebo-controlled, crossover study to evaluate the human abuse liability of solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor.Solriamfetol appears to have abuse potential similar to or lower than phentermine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269642", "endSection": "title" }, { "offsetInBeginSection": 801, "offsetInEndSection": 897, "text": "Results indicate that solriamfetol has dual reuptake inhibition activity at dopamine (DA; IC
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891587", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1364, "text": "Moreover, the wake-promoting effects of solriamfetol are probably owing to activity at DA and NE transporters rather than other neurotransmitter systems, such as histamine or orexin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29891587", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 601, "text": "To evaluate the efficacy and safety of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects, for the treatment of excessive sleepiness in participants with obstructive sleep apnea with current or prior sleep apnea treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30521757", "endSection": "abstract" } ] }, { "body": "What is the difference between the nuclease Cas13a and C2c2", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29575326" ], "ideal_answer": [ "Cas13a was previously called C2c2." ], "type": "summary", "id": "5c928303ecadf2e73f000014", "snippets": [ { "offsetInBeginSection": 461, "offsetInEndSection": 657, "text": "Recently, with the discovery of the nuclease Cas13a (previously called C2c2), molecular biologists have obtained a system that enables sequence-specific cleavage of single-stranded RNA molecules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29575326", "endSection": "abstract" } ] }, { "body": "Phlorotannin is extracted from what plant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30072652", "http://www.ncbi.nlm.nih.gov/pubmed/28946360", "http://www.ncbi.nlm.nih.gov/pubmed/29342865", "http://www.ncbi.nlm.nih.gov/pubmed/22612266", "http://www.ncbi.nlm.nih.gov/pubmed/29344826", "http://www.ncbi.nlm.nih.gov/pubmed/29608860" ], "ideal_answer": [ "Phlorotannin is extracted from Brown Seaweed or brown Algae", "phlorotannins present in brown seaweeds Phlorotannins, phenolic compounds produced exclusively by seaweeds" ], "exact_answer": [ "Brown algea or seaweed" ], "type": "factoid", "id": "5c83fd8e617e120c34000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Brown algae are rich in polyphenolic compounds, phlorotannins, which have been found to possess high in vitro antioxidant capacity, especially DPPH radical scavenging activity, due to the high number of hydroxyl groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28946360", "endSection": "abstract" }, { "offsetInBeginSection": 33, "offsetInEndSection": 72, "text": "phlorotannins present in brown seaweeds", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29342865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Phlorotannins, phenolic compounds produced exclusively by seaweeds", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29344826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Phlorotannin is the collective term for polyphenols derived from brown algae belonging to the genera Ascopyllum, Ecklonia, Eisenia, Fucus and Sargassum etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30072652", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 547, "text": "Here we report that eckmaxol, a phlorotannin extracted from the brown alga Ecklonia maxima, could produce neuroprotective effects in SH-SY5Y cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Antioxidant capacities of phlorotannins extracted from the brown algae Fucus vesiculosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22612266", "endSection": "title" } ] }, { "body": "Where are pannexins localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29932112", "http://www.ncbi.nlm.nih.gov/pubmed/28735901", "http://www.ncbi.nlm.nih.gov/pubmed/25505382", "http://www.ncbi.nlm.nih.gov/pubmed/26386583", "http://www.ncbi.nlm.nih.gov/pubmed/24300303" ], "ideal_answer": [ "Pannexins (Panxs) are a multifaceted family of ion and metabolite channels that play key roles in a number of physiological and pathophysiological settings. These single membrane large-pore channels exhibit a variety of tissue, cell type, and subcellular distributions." ], "exact_answer": [ "In membranes" ], "type": "factoid", "id": "5c7d5fcfd774d04240000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Pannexins are a family of integral membrane proteins with distinct post-translational modifications, sub-cellular localization and tissue distribution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28735901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Pannexins (Panx1, 2, 3) are channel-forming glycoproteins expressed in mammalian tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29932112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Pannexins (Panx) are proteins with a similar membrane topology to connexins, the integral membrane protein of gap junctions. Panx1 channels are generally of major importance in a large number of system and cellular processes and their function has been thoroughly characterized. In contrast, little is known about channel structure and subcellular distribution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26386583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "Pannexins (Panxs) are a multifaceted family of ion and metabolite channels that play key roles in a number of physiological and pathophysiological settings. These single membrane large-pore channels exhibit a variety of tissue, cell type, and subcellular distributions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24300303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Pannexins (Panx) are proteins homologous to the invertebrate gap junction proteins called innexins (Inx) and are traditionally described as transmembrane channels connecting the intracellular and extracellular compartments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25505382", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of cariprazine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29729086", "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "http://www.ncbi.nlm.nih.gov/pubmed/26723167", "http://www.ncbi.nlm.nih.gov/pubmed/30131592", "http://www.ncbi.nlm.nih.gov/pubmed/30322874", "http://www.ncbi.nlm.nih.gov/pubmed/26586950", "http://www.ncbi.nlm.nih.gov/pubmed/28478771", "http://www.ncbi.nlm.nih.gov/pubmed/25083572", "http://www.ncbi.nlm.nih.gov/pubmed/29722587", "http://www.ncbi.nlm.nih.gov/pubmed/27440212", "http://www.ncbi.nlm.nih.gov/pubmed/23320989", "http://www.ncbi.nlm.nih.gov/pubmed/29559781", "http://www.ncbi.nlm.nih.gov/pubmed/23138433" ], "ideal_answer": [ "Cariprazine is a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors. Cariprazine shows also has affinity for 5-HT2B, and 5-HT1A receptors. It also shows moderate affinity toward \u03c31, 5-HT2A, and histamine H1 receptors. It is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder" ], "type": "summary", "id": "5c73ad0c7c78d69471000094", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28478771", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1579, "text": "Two new partial dopamine agonists, brexpiprazole and cariprazine, are now available in addition to aripiprazole. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29559781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "AIM: Cariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29729086", "endSection": "abstract" }, { "offsetInBeginSection": 1361, "offsetInEndSection": 1491, "text": "The contribution of dopamine D2 receptors to cariprazine's in vivo effects is prevalent and that of D3 receptors is less apparent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29729086", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1021, "text": "Expert opinion: Cariprazine shows highest affinity toward D3 receptors, followed by D2, 5-HT2B, and 5-HT1A receptors. It also shows moderate affinity toward \u03c31, 5-HT2A, and histamine H1 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29722587", "endSection": "abstract" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1825, "text": "Conclusions\nIn combination with previous studies, these results suggest that cariprazine has a unique pharmacological profile and distinct dopamine D3 receptor-dependent mechanism of action that may be beneficial in the treatment of schizophrenia, bipolar disorder, and major depressive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Cariprazine Exhibits Anxiolytic and Dopamine D3 Receptor-Dependent Antidepressant Effects in the Chronic Stress Model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Background\nCariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is a new antipsychotic drug recently approved in the United States for the treatment of schizophrenia and bipolar mania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1303, "text": "This antianhedonic-like effect of cariprazine was not observed in D3-knockout mice, suggesting that the cariprazine antidepressant-like activity is mediated by dopamine D3 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "RATIONALE\nCariprazine (RGH-188) is a D\u2083-preferring dopamine D\u2083/D\u2082 receptor partial agonist antipsychotic candidate for the treatment of schizophrenia and bipolar mania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23138433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Cariprazine is a recently developed antipsychotic drug with a partial agonism for the D2 and D3 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "AIM\nCariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29729086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Cariprazine (RGH-188), a D\u2083-preferring dopamine D\u2083/D\u2082 receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23138433", "endSection": "title" }, { "offsetInBeginSection": 284, "offsetInEndSection": 420, "text": "This study used two rodent paradigms to investigate the action of the dopamine D3-preferring D3/D2 receptor partial agonist cariprazine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26723167", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 420, "text": "Cariprazine also displays partial agonism at serotonin [5-hydroxytryptamine (5-HT)] 5-HT1A receptors and antagonism at 5-HT2A and 5-HT2B receptors in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30322874", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 389, "text": "Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440212", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 260, "text": "Cariprazine is a dopamine D3 and D2 receptor partial agonist, with a preference for the D3 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Cariprazine for the Treatment of Schizophrenia: A Review of this Dopamine D3-Preferring D3/D2 Receptor Partial Agonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27440212", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "New developments in the management of schizophrenia and bipolar disorder: potential use of cariprazine.Cariprazine is a recently developed antipsychotic drug with a partial agonism for the D2 and D3 receptors. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586950", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Cariprazine (RGH-188), a D\u2083-preferring dopamine D\u2083/D\u2082 receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats.These results may predict a relapse-preventing action for cariprazine in humans in addition to its already established antipsychotic and antimanic efficacy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23138433", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "Attenuation of anhedonia by cariprazine in the chronic mild stress model of depression.The aim of this study was to evaluate whether chronic treatment with cariprazine, a dopamine D2 and D3 receptor partial agonist with preferential binding to D3 receptors, shows antidepressant-like effects in the chronic mild stress (CMS)-induced anhedonia model. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25083572", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability.Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23320989", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The dopamine D\u2083-preferring D\u2082/D\u2083 dopamine receptor partial agonist, cariprazine, reverses behavioural changes in a rat neurodevelopmental model for schizophrenia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26723167", "endSection": "title" }, { "offsetInBeginSection": 439, "offsetInEndSection": 1146, "text": "Thus, in this study we examined whether the effects of cariprazine are mediated by dopamine D3 receptors.
Methods: Wild-type and D3-knockout mice were exposed to chronic unpredictable stress for up to 26 days, treated daily with vehicle, imipramine (20 mg/kg), aripiprazole (1 and 5 mg/kg), or cariprazine (0.03, 0.1, 0.2, and 0.4 mg/kg), and tested in behavioral assays measuring anhedonia and anxiety-like behaviors.
Results: Results showed that cariprazine significantly attenuated chronic unpredictable stress-induced anhedonic-like behavior in wild-type mice, demonstrating potent antidepressant-like effects comparable with aripiprazole and the tricyclic antidepressant imipramine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1329, "text": "This antianhedonic-like effect of cariprazine was not observed in D3-knockout mice, suggesting that the cariprazine antidepressant-like activity is mediated by dopamine D3 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1864, "text": "Moreover, cariprazine significantly reduced drinking latency in the novelty-induced hypophagia test in wild-type mice, further confirming its antianhedonic-like effect and showing that it also has anxiolytic-like activity.
Conclusions: In combination with previous studies, these results suggest that cariprazine has a unique pharmacological profile and distinct dopamine D3 receptor-dependent mechanism of action that may be beneficial in the treatment of schizophrenia, bipolar disorder, and major depressive disorder.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Background: Cariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is a new antipsychotic drug recently approved in the United States for the treatment of schizophrenia and bipolar mania.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1272, "text": "This antianhedonic-like effect of cariprazine was not observed in D3-knockout mice, suggesting that the cariprazine antidepressant-like activity is mediated by dopamine D3 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1780, "text": "In combination with previous studies, these results suggest that cariprazine has a unique pharmacological profile and distinct dopamine D3 receptor-dependent mechanism of action that may be beneficial in the treatment of schizophrenia, bipolar disorder, and major depressive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 525, "text": "Thus, in this study we examined whether the effects of cariprazine are mediated by dopamine D3 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28531264", "endSection": "abstract" }, { "offsetInBeginSection": -1, "offsetInEndSection": 76, "text": "Binding kinetics of cariprazine and aripiprazole at the dopamine D3 receptor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30131592", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The dissociation behaviours of aripiprazole and cariprazine at the human D2 and D3 receptor are evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30131592", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 553, "text": "Slow dissociation kinetics characterizes aripiprazole and cariprazine at the D2 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30131592", "endSection": "abstract" } ] }, { "body": "Which tool is used to visualise the junction sites of chloroplast genomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29659705" ], "ideal_answer": [ "IRscope is an online program to visualize the junction sites of chloroplast genomes. It allows the users to depict the genetic architecture of up to ten chloroplast genomes in the vicinity of the sites connecting the inverted repeats to the short and long single copy regions. The software and its dependent libraries are fully coded in R and the reflected plot is scaled up to realistic size of nucleotide base pairs in the vicinity of the junction sites. The input of the program is an annotation GenBank (.gb) file, the accession or GI number of the sequence or a DOGMA output file." ], "exact_answer": [ "IRscope" ], "type": "factoid", "id": "5c6acb107c78d6947100001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "IRscope: an online program to visualize the junction sites of chloroplast genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29659705", "endSection": "title" }, { "offsetInBeginSection": 248, "offsetInEndSection": 1297, "text": "Here, we announce a new visualization tool that is specifically designed for chloroplast genomes. It allows the users to depict the genetic architecture of up to ten chloroplast genomes in the vicinity of the sites connecting the inverted repeats to the short and long single copy regions. The software and its dependent libraries are fully coded in R and the reflected plot is scaled up to realistic size of nucleotide base pairs in the vicinity of the junction sites. We introduce a website for easier use of the program and R source code of the software to be used in case of preferences to be changed and integrated into personal pipelines. The input of the program is an annotation GenBank (.gb) file, the accession or GI number of the sequence or a DOGMA output file. The software was tested using over a 100 embryophyte chloroplast genomes and in all cases a reliable output was obtained.Availability and implementation: Source codes and the online suit available at https://irscope.shinyapps.io/irapp/ or https://github.com/Limpfrog/irscope.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29659705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "IRscope: an online program to visualize the junction sites of chloroplast genomes.Source codes and the online suit available at https://irscope.shinyapps.io/irapp/ or https://github.com/Limpfrog/irscope.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29659705", "endSection": "title" } ] }, { "body": "Which curated databases exist for spider-venom toxins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21036864", "http://www.ncbi.nlm.nih.gov/pubmed/19674480", "http://www.ncbi.nlm.nih.gov/pubmed/29069336" ], "ideal_answer": [ "ArachnoServer and its updated version ArachnoServer 2.0 are manually curated databases providing information on the sequence, structure and biological activity of protein toxins from spider venoms." ], "exact_answer": [ [ "ArachnoServer" ], [ "ArachnoServer 2.0" ] ], "type": "list", "id": "5c6d783e7c78d6947100003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "ArachnoServer: a database of protein toxins from spiders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19674480", "endSection": "title" }, { "offsetInBeginSection": 717, "offsetInEndSection": 1703, "text": "We have developed ArachnoServer, a manually curated database that provides detailed information about proteinaceous toxins from spiders. Key features of ArachnoServer include a new molecular target ontology designed especially for venom toxins, the most up-to-date taxonomic information available, and a powerful advanced search interface. Toxin information can be browsed through dynamic trees, and each toxin has a dedicated page summarising all available information about its sequence, structure, and biological activity. ArachnoServer currently manages 567 protein sequences, 334 nucleic acid sequences, and 51 protein structures.CONCLUSION: ArachnoServer provides a single source of high-quality information about proteinaceous spider toxins that will be an invaluable resource for pharmacologists, neuroscientists, toxinologists, medicinal chemists, ion channel scientists, clinicians, and structural biologists. ArachnoServer is available online at http://www.arachnoserver.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19674480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21036864", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1423, "text": "ArachnoServer (www.arachnoserver.org) is a manually curated database providing information on the sequence, structure and biological activity of protein toxins from spider venoms. These proteins are of interest to a wide range of biologists due to their diverse applications in medicine, neuroscience, pharmacology, drug discovery and agriculture. ArachnoServer currently manages 1078 protein sequences, 759 nucleic acid sequences and 56 protein structures. Key features of ArachnoServer include a molecular target ontology designed specifically for venom toxins, current and historic taxonomic information and a powerful advanced search interface. The following significant improvements have been implemented in version 2.0: (i) the average and monoisotopic molecular masses of both the reduced and oxidized form of each mature toxin are provided; (ii) the advanced search feature now enables searches on the basis of toxin mass, external database accession numbers and publication date in ArachnoServer; (iii) toxins can now be browsed on the basis of their phyletic specificity; (iv) rapid BLAST searches based on the mature toxin sequence can be performed directly from the toxin card; (v) private silos can be requested from research groups engaged in venoms-based research, enabling them to easily manage and securely store data during the process of toxin discovery; and (vi) a detailed user manual is now available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21036864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Summary\nArachnoServer is a manually curated database that consolidates information on the sequence, structure, function and pharmacology of spider-venom toxins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "ArachnoServer is a manually curated database that consolidates information on the sequence, structure, function and pharmacology of spider-venom toxins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069336", "endSection": "abstract" } ] }, { "body": "What is the difference between CRISPR-Cas12a and CRISPR-Cpf1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29189942" ], "ideal_answer": [ "CRISPR-Cas12a and CRISPR-Cpf1 refer to the same thing." ], "exact_answer": [ "None" ], "type": "factoid", "id": "5c8fee200101eac87000000f", "snippets": [ { "offsetInBeginSection": 584, "offsetInEndSection": 1035, "text": "n the present review, we attempt to highlight most recent advances in CRISPR-Cpf1 (CRISPR-Cas12a) system in particular, considering ground expeditions of the nature and the biology of this system, introducing novel Cpf1 variants that have broadened the versatility and feasibility of CRISPR-Cpf1 system, and lastly the great impact of the CRISPR-Cpf1 system on the manipulation of the genome of prokaryotic, mammalian, and plant models is summarized. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29189942", "endSection": "abstract" } ] }, { "body": "Please list 2 antitoxin antibodies approved by the FDA for reducing the recurrence of Clostridium difficile infection", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28232034", "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "http://www.ncbi.nlm.nih.gov/pubmed/29760164", "http://www.ncbi.nlm.nih.gov/pubmed/28636484", "http://www.ncbi.nlm.nih.gov/pubmed/28480750", "http://www.ncbi.nlm.nih.gov/pubmed/28865041", "http://www.ncbi.nlm.nih.gov/pubmed/27757389", "http://www.ncbi.nlm.nih.gov/pubmed/25486992", "http://www.ncbi.nlm.nih.gov/pubmed/28730660", "http://www.ncbi.nlm.nih.gov/pubmed/29234211" ], "ideal_answer": [ "The antitoxin antibodies actoxumab and bezlotoxumab bind to and neutralize TcdA and TcdB, respectively. Bezlotoxumab was recently approved by the FDA for reducing the recurrence of CDI." ], "exact_answer": [ [ "bezlotoxumab" ], [ "actoxumab" ] ], "type": "list", "id": "5c851c2675a4a5d219000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "The exotoxins toxin A (TcdA) and toxin B (TcdB) are produced by the bacterial pathogen Clostridium difficile and are responsible for the pathology associated with C. difficile infection (CDI). The antitoxin antibodies actoxumab and bezlotoxumab bind to and neutralize TcdA and TcdB, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28232034", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 378, "text": "Bezlotoxumab was recently approved by the FDA for reducing the recurrence of CDI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28232034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The Monoclonal Antitoxin Antibodies (Actoxumab-Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with Clostridium difficile Infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27757389", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 296, "text": "The antitoxin antibodies actoxumab and bezlotoxumab bind to and neutralize TcdA and TcdB, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28232034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Mechanisms of protection against Clostridium difficile infection by the monoclonal antitoxin antibodies actoxumab and bezlotoxumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25486992", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Bezlotoxumab: anti-toxin B monoclonal antibody to prevent recurrence of Clostridium difficile infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28636484", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B developed by Merck & Co.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Bezlotoxumab (Zinplava\u2122) is a fully human monoclonal antibody against Clostridium difficile toxin B indicated for the prevention of C. difficile infection (CDI) recurrence in patients with a high recurrence risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28865041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B developed by Merck & Co.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27905086", "endSection": "abstract" } ] }, { "body": "List the functions of the protein lactotransferrin.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29756573", "http://www.ncbi.nlm.nih.gov/pubmed/26137081", "http://www.ncbi.nlm.nih.gov/pubmed/25535701" ], "ideal_answer": [ "Lactotransferrin has numerous biological roles, including the regulation of iron absorption and modulation of immune responses, and has anti-microbial, anti-viral, antioxidant, anti-cancer, and anti-inflammatory activities." ], "exact_answer": [ [ "regulation of iron absorption" ], [ "modulation of immune responses" ], [ "anti-microbial" ], [ "anti-viral" ], [ "antioxidant" ], [ "anti-cancer" ], [ "anti-inflammatory" ] ], "type": "list", "id": "5c8bfe25d558e5f23200000f", "snippets": [ { "offsetInBeginSection": 150, "offsetInEndSection": 359, "text": "It has numerous biological roles, including the regulation of iron absorption and modulation of immune responses, and has anti-microbial, anti-viral, antioxidant, anti-cancer, and anti-inflammatory activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29756573", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 629, "text": "The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137081", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 450, "text": "Lactotransferrin (LTF) is a pleiotropic protein, expressed in various body tissues and fluids, which modulates the host immune-inflammatory response and bone metabolism, and might be involved in dental implant osseointegration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25535701", "endSection": "abstract" } ] }, { "body": "Does Axitinib prolong survival of Pancreatic Cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21306953", "http://www.ncbi.nlm.nih.gov/pubmed/24328549", "http://www.ncbi.nlm.nih.gov/pubmed/25647781" ], "ideal_answer": [ "No. The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer." ], "exact_answer": "no", "type": "yesno", "id": "5c73ad347c78d69471000098", "snippets": [ { "offsetInBeginSection": 1673, "offsetInEndSection": 1853, "text": "CONCLUSIONS: Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25647781", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 1257, "text": "RESULTS: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25647781", "endSection": "abstract" }, { "offsetInBeginSection": 1757, "offsetInEndSection": 2144, "text": "At an interim analysis in January, 2009, the independent data monitoring committee concluded that the futility boundary had been crossed. Median overall survival was 8\u00b75 months (95% CI 6\u00b79-9\u00b75) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8\u00b73 months (6\u00b79-10\u00b73) for gemcitabine plus placebo (n=316; hazard ratio 1\u00b7014, 95% CI 0\u00b7786-1\u00b7309; one-sided p=0\u00b75436). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21306953", "endSection": "abstract" }, { "offsetInBeginSection": 2417, "offsetInEndSection": 2538, "text": "INTERPRETATION: The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21306953", "endSection": "abstract" }, { "offsetInBeginSection": 2423, "offsetInEndSection": 2542, "text": "INTERPRETATION\nThe addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21306953", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1453, "text": "However, as with other tyrosine kinase inhibitors of the same class, axitinib does not prolong overall survival; therefore, selection of second-line tyrosine kinase inhibitor therapy, including axitinib, must be carefully considered to maximize outcomes for each patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24328549", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1858, "text": "CONCLUSIONS\nAxitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25647781", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1285, "text": "Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25647781", "endSection": "abstract" }, { "offsetInBeginSection": 1645, "offsetInEndSection": 1812, "text": "Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25647781", "endSection": "abstract" }, { "offsetInBeginSection": 2373, "offsetInEndSection": 2477, "text": "The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21306953", "endSection": "abstract" } ] }, { "body": "Which Python tool has been developed for network-based stratification of tumor mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29608663" ], "ideal_answer": [ "PyNBS is a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes." ], "exact_answer": [ "PyNBS" ], "type": "factoid", "id": "5c6ad2997c78d69471000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "pyNBS: a Python implementation for network-based stratification of tumor mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608663", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 217, "text": "We present pyNBS: a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Summary\nWe present pyNBS: a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "pyNBS: a Python implementation for network-based stratification of tumor mutations.The package, along with examples and data, can be downloaded and installed from the URL https://github.com/idekerlab/pyNBS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608663", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Summary: We present pyNBS: a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "We present pyNBS: a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608663", "endSection": "abstract" } ] }, { "body": "Through which protein interaction does MLP regulate F-actin dynamics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19752190" ], "ideal_answer": [ "The interaction of MLP with CFL2 has direct implications in actin cytoskeleton dynamics in regulating CFL2-dependent F-actin depolymerization, with maximal depolymerization enhancement at an MLP/CFL2 molecular ratio of 2:1. Deregulation of this interaction by intracellular pH variations, CFL2 phosphorylation, MLP or CFL2 gene mutations, or expression changes, as observed in a range of cardiac and skeletal myopathies, could impair F-actin depolymerization, leading to sarcomere dysfunction and disease." ], "exact_answer": [ "Cofilin 2" ], "type": "factoid", "id": "5c8fef490101eac870000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19752190", "endSection": "title" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1462, "text": "This interaction has direct implications in actin cytoskeleton dynamics in regulating CFL2-dependent F-actin depolymerization, with maximal depolymerization enhancement at an MLP/CFL2 molecular ratio of 2:1. Deregulation of this interaction by intracellular pH variations, CFL2 phosphorylation, MLP or CFL2 gene mutations, or expression changes, as observed in a range of cardiac and skeletal myopathies, could impair F-actin depolymerization, leading to sarcomere dysfunction and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19752190", "endSection": "abstract" } ] }, { "body": "Is there any association between suicide and autism in adolescents, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27956832", "http://www.ncbi.nlm.nih.gov/pubmed/24201088", "http://www.ncbi.nlm.nih.gov/pubmed/28872268", "http://www.ncbi.nlm.nih.gov/pubmed/25200592", "http://www.ncbi.nlm.nih.gov/pubmed/29854129", "http://www.ncbi.nlm.nih.gov/pubmed/25084822", "http://www.ncbi.nlm.nih.gov/pubmed/17885828", "http://www.ncbi.nlm.nih.gov/pubmed/29706156", "http://www.ncbi.nlm.nih.gov/pubmed/23666287" ], "ideal_answer": [ "Adults with autism spectrum disorder (ASD) are at increased risk of suicide compared to the general population." ], "exact_answer": "yes", "type": "yesno", "id": "5c5217fd7e3cb0e231000005", "snippets": [ { "offsetInBeginSection": 609, "offsetInEndSection": 957, "text": ": In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25200592", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1212, "text": "Suicide attempts are accompanied by a willingness for death and can lead to suicide. They are more common in high-functioning autism and Asperger subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25200592", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 1208, "text": " A total sample of 10 adolescents and young adults diagnosed with AS was obtained. The high proportion of respondents with scores above the cutoff point on the overt victimization and relational victimization scales suggests that these adolescents and young adults experienced high levels of victimization. Of the sample, 20 percent met criteria for a diagnosis of Major Depressive Disorder, 30 percent met criteria for Generalized Anxiety Disorder and 50 percent had clinically significant level of suicidal ideation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17885828", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 177, "text": "Previous studies reported a high prevalence of depression among patients with autism spectrum disorder (ASD) and suggested a relationship between ASD and suicidality", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28872268", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1270, "text": "Patients with ASD had an increased risk of suicide attempts compared with those without ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28872268", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 326, "text": "The suicidal behaviors are frequently observed in the adolescents and adults with an ASD without intellectual deficience. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Suicide is a major problem in Western society. However we have very little understanding of suicidal behaviour among individuals with autism spectrum disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24201088", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 694, "text": "The available research provides little empirical evidence for the processes underlying suicidal behaviour in adolescents and young adults with autism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24201088", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 395, "text": " The present study aims to assess the rate of suicidality (suicidal ideation, behaviors and attempts) and associated risk factors for suicidality in high functioning ASD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27956832", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 225, "text": "here is a lack of clinical awareness on suicidal behaviors of children and adolescents with autism spectrum disorder (ASD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27956832", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 114, "text": "suicidality in children and adolescents with diagnosis of high functioning autism spectrum disorder ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27956832", "endSection": "title" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1771, "text": "Consistent with the previous findings, rate of suicidality is higher in individuals with ASD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27956832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Detection of Suicidality in Adolescents with Autism Spectrum Disorders", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29854129", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Over 15% of young people with autism spectrum disorders (ASD) will contemplate or attempt suicide during adolescence. Yet,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29854129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Until recently, suicidality in autism spectrum disorder (ASD) was rarely discussed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706156", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 67, "text": "Suicidality in Autism Spectrum Disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706156", "endSection": "title" }, { "offsetInBeginSection": 172, "offsetInEndSection": 376, "text": "highlighted not only that suicidal thoughts and suicide attempts can occur in adolescents and young adults with ASD, but also that suicidality is likely more common in ASD than in the general population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706156", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 757, "text": "The emerging studies indicate that the increased risk of self-injurious behavior in younger and less cognitively able children with ASD3,4 is matched by an increased risk of suicidality in those at a more advanced developmental level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706156", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 959, "text": "RESULTS\nIn all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25200592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Risk of Suicide Attempts Among Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Follow-Up Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28872268", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Although the suicide risk of autism spectrum disorder (ASD) has been suggested to be higher than previously recognized, there are few case reports focusing on the process for preventing suicide reattempts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25084822", "endSection": "abstract" } ] }, { "body": "Is lactotransferrin a tumour suppressor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23069661", "http://www.ncbi.nlm.nih.gov/pubmed/25370482", "http://www.ncbi.nlm.nih.gov/pubmed/18697201", "http://www.ncbi.nlm.nih.gov/pubmed/23479198", "http://www.ncbi.nlm.nih.gov/pubmed/26137081" ], "ideal_answer": [ "Lactotransferrin (LTF) has been confirmed to act as a tumor suppressor in multiple cancers." ], "exact_answer": "yes", "type": "yesno", "id": "5c8c05c70101eac870000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "LTF (lactotransferrin, or lactoferrin) plays important role in innate immunity, and its anti-tumor function has also been reported in multiple cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23479198", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 310, "text": "We previously reported that LTF is significantly down-regulated in nasopharyngeal carcinoma (NPC) and acts as a tumor suppressor by suppressing AKT signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23479198", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 628, "text": "The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137081", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 102, "text": "Lactotransferrin (LTF) has been confirmed to act as a tumor suppressor in multiple cancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25370482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23069661", "endSection": "title" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1621, "text": "LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18697201", "endSection": "abstract" } ] }, { "body": "What is CVT-301?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27733560", "http://www.ncbi.nlm.nih.gov/pubmed/27090868", "http://www.ncbi.nlm.nih.gov/pubmed/28494719", "http://www.ncbi.nlm.nih.gov/pubmed/29161531", "http://www.ncbi.nlm.nih.gov/pubmed/27743318", "http://www.ncbi.nlm.nih.gov/pubmed/27345931", "http://www.ncbi.nlm.nih.gov/pubmed/30479171" ], "ideal_answer": [ "CVT-301 is inhaled levodopa (LD) formulation for development as a self-administered treatment for relief of OFF periods in Parkinson's disease. CVT-301 provided rapid improvement of motor function, and daily OFF time was significantly reduced at the higher dose." ], "type": "summary", "id": "5c72bfcd7c78d6947100007a", "snippets": [ { "offsetInBeginSection": 1312, "offsetInEndSection": 1586, "text": "Further approaches to enhance LD efficacy are focused on new non-oral administration routes, including nasal, intra-duodenal, intrapulmonary (CVT-301) and subcutaneous (ND0612), as well as on novel ER formulations, including IPX066, which recently concluded phase III trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28494719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29161531", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "BACKGROUND: CVT-301, an inhaled levodopa (LD) formulation, is under development for relief of OFF periods in Parkinson's disease (PD). Previously, we reported that CVT-301 improved OFF symptoms relative to placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29161531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Pharmacokinetic drug evaluation of CVT-301 for the treatment of Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479171", "endSection": "title" }, { "offsetInBeginSection": 538, "offsetInEndSection": 702, "text": "Areas covered: CVT-301 is a self-administered dry powder aerosol inhaled formulation of LD that is being developed as a self-administered treatment for OFF periods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479171", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 692, "text": "During a placebo-controlled trial of an inhaled levodopa formulation, CVT-301, in PD patients with \u22652 h/d of OFF time, spirometry was performed by American Thoracic Society (ATS) guidelines at screening and throughout the 4-week treatment period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27345931", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1264, "text": "ND0612 is a proprietary liquid formulation of LD/CD that enables subcutaneous administration via a small patch-pump device, and CVT-301 is a levodopa inhalation powder with rapid onset of action; both are currently in active studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27743318", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 402, "text": "CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations between doses of standard oral levodopa) in patients with Parkinson's disease (PD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27733560", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 367, "text": "CVT-301 is a levodopa inhalation powder with the potential for rapid onset of action. The objective of this study was to evaluate CVT-301 self-administered by PD patients to relieve OFF episodes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27090868", "endSection": "abstract" }, { "offsetInBeginSection": 1377, "offsetInEndSection": 1547, "text": "CONCLUSIONS: CVT-301 self-administered during OFF episodes provided rapid improvement of motor function, and daily OFF time was significantly reduced at the higher dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27090868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "BACKGROUND\nCVT-301, an inhaled levodopa (LD) formulation, is under development for relief of OFF periods in Parkinson's disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29161531", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 256, "text": "CVT-301 is a levodopa inhalation powder with the potential for rapid onset of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27090868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27090868", "endSection": "title" }, { "offsetInBeginSection": 165, "offsetInEndSection": 401, "text": "CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations between doses of standard oral levodopa) in patients with Parkinson's disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27733560", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 688, "text": "Areas covered: CVT-301 is a self-administered dry powder aerosol inhaled formulation of LD that is being developed as a self-administered treatment for OFF periods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479171", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 245, "text": "CVT-301 is a levodopa inhalation powder with the potential for rapid onset of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27090868", "endSection": "abstract" } ] }, { "body": "Are there tools for visualizing and processing long-read sequencing data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29547981" ], "ideal_answer": [ "Yes. Tools such as NanoPack for instance have been developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences." ], "exact_answer": "yes", "type": "yesno", "id": "5c6ad3be7c78d69471000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "NanoPack: visualizing and processing long-read sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547981", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 638, "text": "Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.Availability and implementation: The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License. The source code can be found at https://github.com/wdecoster/nanopack, together with links to separate scripts and their documentation. The scripts are compatible with Linux, Mac OS and the MS Windows 10 subsystem for Linux and are available as a graphical user interface, a web service at http://nanoplot.bioinf.be and command line tools.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Summary\nHere we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "NanoPack: visualizing and processing long-read sequencing data.Supplementary data are available at Bioinformatics online.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547981", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Summary: Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.
Availability and implementation: The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547981", "endSection": "abstract" } ] }, { "body": "Name siRNA drugs that have entered phase 2-3 clinical trials (by 2019).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28389707" ], "ideal_answer": [ "siRNAs that have entered phase 2-3 clinical trials by 2019 include PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3)." ], "exact_answer": [ [ "PF-04523655" ], [ "TKM-080301" ], [ "Atu027" ], [ "SYL040012" ], [ "SYL1001" ], [ "siG12D-LODER" ], [ "QPI-1002" ], [ "QPI-1007" ], [ "patisiran" ] ], "type": "list", "id": "5c900983ecadf2e73f000002", "snippets": [ { "offsetInBeginSection": 434, "offsetInEndSection": 728, "text": " This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials. The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28389707", "endSection": "abstract" } ] }, { "body": "Where is fatty acid binding protein 2 expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29032508", "http://www.ncbi.nlm.nih.gov/pubmed/17960769", "http://www.ncbi.nlm.nih.gov/pubmed/20670215", "http://www.ncbi.nlm.nih.gov/pubmed/18634911", "http://www.ncbi.nlm.nih.gov/pubmed/26547205", "http://www.ncbi.nlm.nih.gov/pubmed/18440731" ], "ideal_answer": [ "fatty acid binding protein 2 is expressed by intestinal epithelial cells" ], "exact_answer": [ "intestinal epithelial cells" ], "type": "factoid", "id": "5c8d15cf0101eac870000009", "snippets": [ { "offsetInBeginSection": 15, "offsetInEndSection": 75, "text": " human intestinal fatty acid binding protein 2 gene (FABP2) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18634911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The human fatty acid binding protein (FABP2) is involved in intestinal absorption and intracellular trafficking of long-chain fatty acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18440731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The human intestinal fatty acid binding protein 2 (FABP2) mediates fat absorption by binding and intracellular trafficking of long-chain free fatty acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17960769", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 905, "text": "intestinal epithelial cells [FABP2 (fatty acid binding protein 2),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670215", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1127, "text": "enterocyte markers like villin, zonula occluden (ZO1), fatty acid binding protein 2 (FABP2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29032508", "endSection": "abstract" } ] }, { "body": "Which gene mutation is associated with Woodhouse Sakati syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30409855", "http://www.ncbi.nlm.nih.gov/pubmed/26664771", "http://www.ncbi.nlm.nih.gov/pubmed/26612766", "http://www.ncbi.nlm.nih.gov/pubmed/29574468", "http://www.ncbi.nlm.nih.gov/pubmed/24464444" ], "ideal_answer": [ "DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements." ], "exact_answer": [ "DCAF17" ], "type": "factoid", "id": "5c72f5247c78d6947100007e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Phenotypic Variability of c.436delC DCAF17 Gene Mutation in Woodhouse-Sakati Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29574468", "endSection": "title" }, { "offsetInBeginSection": 606, "offsetInEndSection": 801, "text": " CASE REPORT We illustrate the phenotypic variability of 5 patients with WSS due to the previously reported homozygous single nucleotide deletion c.436delC in the DCAF17 gene, identified in 2008.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29574468", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 261, "text": "The disease is caused by biallelic pathogenic variants in the DCAF17 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30409855", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 363, "text": "Sequence variants in the gene DCAF17, encoding nucleolar substrate receptor, were identified as the underlying cause of inherited WSS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26612766", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26612766", "endSection": "title" }, { "offsetInBeginSection": 698, "offsetInEndSection": 873, "text": "Exome sequencing identified a novel single base deletion variant (c.270delA; K90Nfs8*) in third exon of the gene DCAF17 (RefSeq; NM_025000), resulting in a truncated protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26612766", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1134, "text": "DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26664771", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 316, "text": "The responsible gene, DCAF17 located on chromosome 2q31.1, was discovered in 2008 and to date nine mutations have been reported in the literature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24464444", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1133, "text": "DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26664771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Phenotypic Variability of c.436delC DCAF17 Gene Mutation in Woodhouse-Sakati Syndrome.BACKGROUND Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive genetic condition that was first described in 1983. Since its original description, approximately 50 cases have been reported with various clinical signs and symptoms. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29574468", "endSection": "title" }, { "offsetInBeginSection": 693, "offsetInEndSection": 1060, "text": "CASE REPORT We illustrate the phenotypic variability of 5 patients with WSS due to the previously reported homozygous single nucleotide deletion c.436delC in the DCAF17 gene, identified in 2008. Despite identical genetic alteration, our 5 patients had various clinical features among them and compared with previously reported cases with the same pathogenic mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29574468", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 237, "text": "The disease is caused by biallelic pathogenic variants in the DCAF17 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30409855", "endSection": "abstract" } ] }, { "body": "Mention computational tools that have been developed for alternative polyadenylation (APA) sites analysis", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27446120", "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "http://www.ncbi.nlm.nih.gov/pubmed/29733382", "http://www.ncbi.nlm.nih.gov/pubmed/25506822" ], "ideal_answer": [ "TAPAS, PlantAPA and IntMAP" ], "exact_answer": [ [ "TAPAS" ], [ "PlantAPA" ], [ "IntMAP" ], [ "VAAPA" ] ], "type": "list", "id": "5c6b15467c78d69471000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "TAPAS: tool for alternative polyadenylation site analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "title" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1750, "text": "We propose a new tool, called TAPAS, for detecting novel APA sites from RNA-Seq data. It can deal with more than two APA sites in a gene as well as APA sites that occur before the last exon. The tool is based on an existing method for finding change points in time series data, but some filtration techniques are also adopted to remove change points that are likely false APA sites. It is then extended to identify APA sites that are expressed differently between two biological samples and genes that contain 3' UTRs with shortening/lengthening events. Our extensive experiments on simulated and real RNA-Seq data demonstrate that TAPAS outperforms the existing tools for APA site detection or shortening/lengthening analysis significantly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "PlantAPA: A Portal for Visualization and Analysis of Alternative Polyadenylation in Plants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27446120", "endSection": "title" }, { "offsetInBeginSection": 215, "offsetInEndSection": 1812, "text": "Increasing numbers of poly(A) sites collected in various plant species demand new methods and tools to access and mine these data. We have created an open-access web service called PlantAPA (http://bmi.xmu.edu.cn/plantapa) to visualize and analyze genome-wide poly(A) sites in plants. PlantAPA provides various interactive and dynamic graphics and seamlessly integrates a genome browser that can profile heterogeneous cleavage sites and quantify expression patterns of poly(A) sites across different conditions. Particularly, through PlantAPA, users can analyze poly(A) sites in extended 3' UTR regions, intergenic regions, and ambiguous regions owing to alternative transcription or RNA processing. In addition, it also provides tools for analyzing poly(A) site selections, 3' UTR lengthening or shortening, non-canonical APA site switching, and differential gene expression between conditions, making it more powerful for the study of APA-mediated gene expression regulation. More importantly, PlantAPA offers a bioinformatics pipeline that allows users to upload their own short reads or ESTs for poly(A) site extraction, enabling users to further explore poly(A) site selection using stored PlantAPA poly(A) sites together with their own poly(A) site datasets. To date, PlantAPA hosts the largest database of APA sites in plants, including Oryza sativa, Arabidopsis thaliana, Medicago truncatula, and Chlamydomonas reinhardtii. As a user-friendly web service, PlantAPA will be a valuable addition to the community of biologists studying APA mechanisms and gene expression regulation in plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27446120", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 1590, "text": "In our recent RNA-seq experiments using cells with hyper-activated mammalian target of rapamycin (mTOR), we found that cellular mTOR activation leads to transcriptome-wide alternative polyadenylation (APA), resulting in the activation of multiple cellular pathways. Here, we developed a novel bioinformatics algorithm, IntMAP, which integrates RNA-Seq and PolyA Site (PAS)-Seq data for a comprehensive characterization of APA events. By applying IntMAP to the datasets from cells with hyper-activated mTOR, we identified novel APA events that could otherwise not be identified by either profiling method alone. Several transcription factors including Cebpg (CCAAT/enhancer binding protein gamma) were among the newly discovered APA transcripts, indicating that diverse transcriptional networks may be regulated by mTOR-coordinated APA. The prevention of APA in Cebpg using the CRISPR/cas9-mediated genome editing tool showed that mTOR-driven 3'-UTR shortening in Cebpg is critical in protecting cells from endoplasmic reticulum (ER) stress. Taken together, we present IntMAP as a new bioinformatics algorithm for APA analysis by which we expand our understanding of the physiological role of mTOR-coordinated APA events to ER stress response. IntMAP toolbox is available at http://compbio.cs.umn.edu/IntMAP/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29733382", "endSection": "abstract" }, { "offsetInBeginSection": 1564, "offsetInEndSection": 1751, "text": "Our extensive experiments on simulated and real RNA-Seq data demonstrate that TAPAS outperforms the existing tools for APA site detection or shortening/lengthening analysis significantly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1095, "text": "Results\nWe propose a new tool, called TAPAS, for detecting novel APA sites from RNA-Seq data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "PlantAPA: A Portal for Visualization and Analysis of Alternative Polyadenylation in Plants.Alternative polyadenylation (APA) is an important layer of gene regulation that produces mRNAs that have different 3' ends and/or encode diverse protein isoforms. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27446120", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "VAAPA: a web platform for visualization and analysis of alternative polyadenylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506822", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "TAPAS: tool for alternative polyadenylation site analysis.Supplementary data are available at Bioinformatics online.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "title" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1112, "text": "Furthermore, the tools are unable to integrate the analysis of shortening/lengthening events with APA site detection.
Results: We propose a new tool, called TAPAS, for detecting novel APA sites from RNA-Seq data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "abstract" }, { "offsetInBeginSection": 1581, "offsetInEndSection": 1945, "text": "Our extensive experiments on simulated and real RNA-Seq data demonstrate that TAPAS outperforms the existing tools for APA site detection or shortening/lengthening analysis significantly.
Availability and implementation: https://github.com/arefeen/TAPAS.
Supplementary information: Supplementary data are available at Bioinformatics online.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1730, "text": "Our extensive experiments on simulated and real RNA-Seq data demonstrate that TAPAS outperforms the existing tools for APA site detection or shortening/lengthening analysis significantly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1074, "text": "We propose a new tool, called TAPAS, for detecting novel APA sites from RNA-Seq data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30052912", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 343, "text": "Here, a web platform for visualization and analysis of alternative polyadenylation (VAAPA) was developed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506822", "endSection": "abstract" } ] }, { "body": "What is patisiran?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30251172" ], "ideal_answer": [ "Patisiran (ONPATTRO\u2122) is a double-stranded small interfering RNA encapsulated in a lipid nanoparticle for delivery to hepatocytes. By specifically binding to a genetically conserved sequence in the 3' untranslated region of mutant and wild-type transthyretin (TTR) messenger RNA, patisiran causes its degradation (via RNA interference) and subsequently a reduction in serum TTR protein levels and tissue TTR protein deposits. It has been approved in the USA for the treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis (hATTR) in adults and subsequently approved in the EU for the treatment of hATTR in adults with stage 1 or 2 polyneuropathy." ], "type": "summary", "id": "5c900a9becadf2e73f000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 722, "text": "Patisiran (ONPATTRO\u2122) is a double-stranded small interfering RNA encapsulated in a lipid nanoparticle for delivery to hepatocytes. By specifically binding to a genetically conserved sequence in the 3' untranslated region of mutant and wild-type transthyretin (TTR) messenger RNA, patisiran causes its degradation (via RNA interference) and subsequently a reduction in serum TTR protein levels and tissue TTR protein deposits. Patisiran has been developed by Alnylam Pharmaceuticals; it was recently approved in the USA for the treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis (hATTR) in adults and subsequently approved in the EU for the treatment of hATTR in adults with stage 1 or 2 polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30251172", "endSection": "abstract" } ] }, { "body": "Losigamone can be used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23683707", "http://www.ncbi.nlm.nih.gov/pubmed/21429248", "http://www.ncbi.nlm.nih.gov/pubmed/9421300", "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "http://www.ncbi.nlm.nih.gov/pubmed/15638775", "http://www.ncbi.nlm.nih.gov/pubmed/20650103", "http://www.ncbi.nlm.nih.gov/pubmed/14704462", "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "http://www.ncbi.nlm.nih.gov/pubmed/12972172", "http://www.ncbi.nlm.nih.gov/pubmed/15112861", "http://www.ncbi.nlm.nih.gov/pubmed/21549021", "http://www.ncbi.nlm.nih.gov/pubmed/22696384" ], "ideal_answer": [ "Losigamone is sometimes used as an add-on therapy for epilepsy." ], "exact_answer": [ "epilepsy" ], "type": "factoid", "id": "5c73acec7c78d69471000086", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Losigamone add-on therapy for focal epilepsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "title" }, { "offsetInBeginSection": 292, "offsetInEndSection": 463, "text": "In recent years, many newer AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is one of these drugs and is the focus of this systematic review. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 1901, "offsetInEndSection": 2242, "text": "For the efficacy outcomes, results did show that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16, 95% CI 1.28 to 3.67). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 2922, "offsetInEndSection": 3137, "text": "AUTHORS' CONCLUSIONS: The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Losigamone add-on therapy for partial epilepsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "title" }, { "offsetInBeginSection": 269, "offsetInEndSection": 442, "text": "In recent years, many newer AEDs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 1970, "offsetInEndSection": 2302, "text": "For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 2966, "offsetInEndSection": 3178, "text": "AUTHORS' CONCLUSIONS: The results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 532, "text": "For topiramate, felbamate, retigabine, losigamone and stiripentol, GABAAR modulation is one of several possible antiseizure mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23683707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "Losigamone add-on therapy for partial epilepsy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 465, "text": "In recent years, many newer antiepileptic drugs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 1809, "offsetInEndSection": 2141, "text": "For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.75; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 2792, "offsetInEndSection": 3004, "text": "AUTHORS' CONCLUSIONS: The results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 2428, "text": "CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or generalised epilepsy who are in remission; behavioural and psychological treatments for partial or generalised epilepsy (biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, relaxation therapy (alone or plus behavioural modification therapy, yoga); and surgery for drug-resistant temporal lobe epilepsy ( lesionectomy, temporal lobectomy, vagus nerve stimulation as adjunctive therapy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21549021", "endSection": "abstract" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 2428, "text": "CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or generalised epilepsy who are in remission; behavioural and psychological treatments for partial or generalised epilepsy (biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, relaxation therapy (alone or plus behavioural modification therapy, yoga); and surgery for drug-resistant temporal lobe epilepsy ( lesionectomy, temporal lobectomy, vagus nerve stimulation as adjunctive therapy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21429248", "endSection": "abstract" }, { "offsetInBeginSection": 1439, "offsetInEndSection": 1770, "text": "This is supplemented by the mechanisms of drug action at these important anticonvulsant targets for classical and clinically relevant compounds (e.g. phenytoin, ethosuximide) as well as some important second generation drugs (e.g. gabapentin, levetiracetam) and novel experimental agents (e.g. retigabine, losigamone, safinamide). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15638775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "OBJECTIVES: The influence of the new antiepileptic drug losigamone (CAS 112856-44-7/123783-52-8) on the pharmacokinetics of a combined oral contraceptive containing ethinylestradiol (CAS 57-63-6) and levonorgestrel (CAS 797-63-7) was investigated in 16 healthy women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15112861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The objective of the study was to investigate the efficacy and safety of two different dosages of Losigamone (LSG) in add-on treatment of partial seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12972172", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1664, "text": "Based on the study's results, LSG is an effective and safe add-on drug for refractory partial epilepsy in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12972172", "endSection": "abstract" }, { "offsetInBeginSection": 2804, "offsetInEndSection": 3014, "text": "AUTHORS' CONCLUSIONS\nThe results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 583, "text": "OBJECTIVES\nTo investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1088, "text": "SELECTION CRITERIA\nRandomized controlled add-on trials comparing losigamone with placebo for partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 464, "text": "In recent years, many newer antiepileptic drugs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 1622, "offsetInEndSection": 1714, "text": "Both trials assessed losigamone 1200 or 1500 mg/d as an add-on therapy for partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 2934, "offsetInEndSection": 3147, "text": "AUTHORS' CONCLUSIONS\nThe results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 2978, "offsetInEndSection": 3188, "text": "AUTHORS' CONCLUSIONS\nThe results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 718, "text": "OBJECTIVES\nTo investigate the efficacy and safety of losigamone when used as an add-on therapy for focal epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 1818, "offsetInEndSection": 2149, "text": "For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.75; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 771, "text": "Five drugs (carbamazepine, diazepam, phenobarbital, phenytoin and valproate), currently used in the treatment of epileptic patients, were tested together with losigamone, a recently developed anticonvulsant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20650103", "endSection": "abstract" }, { "offsetInBeginSection": 2544, "offsetInEndSection": 2801, "text": "A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/d) is associated with a greater reduction in seizure frequency than lower doses, but is also associated with more dropouts due to adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 86, "text": "Losigamone is a novel anticonvulsant the mechanism of action of which is not known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9421300", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 679, "text": "OBJECTIVES\nTo investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1146, "text": "SELECTION CRITERIA\nRandomized controlled, add-on trials comparing losigamone with placebo for focal epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 1645, "offsetInEndSection": 1758, "text": "Based on the study's results, LSG is an effective and safe add-on drug for refractory partial epilepsy in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12972172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Losigamone add-on therapy for partial epilepsy.The results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Losigamone add-on therapy for partial epilepsy.The results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Losigamone add-on therapy for focal epilepsy.The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Efficacy and safety of Losigamone in partial seizures: a randomized double-blind study.The objective of the study was to investigate the efficacy and safety of two different dosages of Losigamone (LSG) in add-on treatment of partial seizures. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12972172", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Perspectives of losigamone in epilepsy treatment.Patients with drug resistant epilepsy represent about 40% of the whole population of epileptic patients. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14704462", "endSection": "title" }, { "offsetInBeginSection": 449, "offsetInEndSection": 949, "text": "This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6).
OBJECTIVES: To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy.
SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (16 February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 16 February 2015) and MEDLINE (Ovid, 1946 to 16 February 2015).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 2694, "offsetInEndSection": 2883, "text": "The results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 559, "text": "To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 655, "text": "To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 694, "text": "To investigate the efficacy and safety of losigamone when used as an add-on therapy for focal epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1529, "text": "In clinical trial, losigamone proved to have satisfactory effectiveness and good tolerance in the treatment of partial and secondary generalized seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14704462", "endSection": "abstract" }, { "offsetInBeginSection": 2868, "offsetInEndSection": 3057, "text": "The results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26661741", "endSection": "abstract" }, { "offsetInBeginSection": 2824, "offsetInEndSection": 3016, "text": "The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355908", "endSection": "abstract" }, { "offsetInBeginSection": 1710, "offsetInEndSection": 2041, "text": "For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.75; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22696384", "endSection": "abstract" } ] }, { "body": "Which curated data resources for ChIP-seq data are available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24174536", "http://www.ncbi.nlm.nih.gov/pubmed/24253304", "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "http://www.ncbi.nlm.nih.gov/pubmed/29069466" ], "ideal_answer": [ "The MGA repository, Cistrome Data Browser, CR Cistrome and GeneProf data." ], "exact_answer": [ [ "MGA repository" ], [ "Cistrome Data Browser" ], [ "CR Cistrome" ], [ "GeneProf data" ] ], "type": "list", "id": "5c6bda9d7c78d69471000031", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "MGA repository: a curated data resource for ChIP-seq and other genome annotated data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069466", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The Mass Genome Annotation (MGA) repository is a resource designed to store published next generation sequencing data and other genome annotation data (such as gene start sites, SNPs, etc.) in a completely standardised format.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 1188, "text": "To overcome this challenge, we built the Cistrome database, a collection of ChIP-seq and chromatin accessibility data (DNase-seq and ATAC-seq) published before January 1, 2016, including 13 366 human and 9953 mouse samples. All the data have been carefully curated and processed with a streamlined analysis pipeline and evaluated with comprehensive quality control metrics. We have also created a user-friendly web server for data query, exploration and visualization. The resulting Cistrome DB (Cistrome Data Browser), available online at http://cistrome.org/db, is expected to become a valuable resource for transcriptional and epigenetic regulation studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "CR Cistrome: a ChIP-Seq database for chromatin regulators and histone modification linkages in human and mouse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24253304", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "GeneProf data: a resource of curated, integrated and reusable high-throughput genomics experiments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24174536", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "CR Cistrome: a ChIP-Seq database for chromatin regulators and histone modification linkages in human and mouse.Diversified histone modifications (HMs) are essential epigenetic features. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24253304", "endSection": "title" } ] }, { "body": "How many pseudokinases are there in the human kinome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29254998" ], "ideal_answer": [ "There are approximately 50 pseudokinases in the human kinome." ], "exact_answer": [ "Approximately 50" ], "type": "factoid", "id": "5c909b6cecadf2e73f000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The human protein kinome comprises 535 proteins that, with the exception of approximately 50 pseudokinases, control intracellular signaling networks by catalyzing the phosphorylation of multiple protein substrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29254998", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Inclisiran?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28736830", "http://www.ncbi.nlm.nih.gov/pubmed/29424317", "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "http://www.ncbi.nlm.nih.gov/pubmed/29516321", "http://www.ncbi.nlm.nih.gov/pubmed/28306389", "http://www.ncbi.nlm.nih.gov/pubmed/30487231", "http://www.ncbi.nlm.nih.gov/pubmed/27959715", "http://www.ncbi.nlm.nih.gov/pubmed/29735484", "http://www.ncbi.nlm.nih.gov/pubmed/29850255", "http://www.ncbi.nlm.nih.gov/pubmed/30011788", "http://www.ncbi.nlm.nih.gov/pubmed/30375244" ], "ideal_answer": [ "Inclisiran, a novel, synthetic, siRNA molecule, inhibits PCSK9 synthesis in hepatocytes. Inclisiran targets intracellular PCSK9 synthesis specifically, resulting in a dose-dependent, long-term, significant reduction in LDL-C." ], "type": "summary", "id": "5c73ad047c78d6947100008e", "snippets": [ { "offsetInBeginSection": 905, "offsetInEndSection": 1081, "text": "Inclisiran is a promising RNA-based therapy that promotes the degradation of PCSK9 mRNA transcripts and has similar efficacy to mAbs, but with a much longer duration of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736830", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 523, "text": "Recently marketed monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown the way towards innovation, while other ways of PCSK9 inhibition like small interfering RNA (Inclisiran) are already being tested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29424317", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 658, "text": " Inclisiran, a novel, synthetic, siRNA molecule, inhibits PCSK9 synthesis in hepatocytes. Inclisiran targets intracellular PCSK9 synthesis specifically, resulting in a dose-dependent, long-term, significant reduction in LDL-C. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND: To our knowledge, inclisiran was the first agent composed of small interfering RNAs (siRNAs) to be preliminarily used to reduce proatherogenic lipoprotein cholesterol levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29516321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "BACKGROUND: The ORION-1 trial (Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol [LDL-C]) demonstrated that inclisiran, an siRNA therapeutic that targets protease proprotein convertase subtilisin/kexin type 9 mRNA within hepatocytes, produces significant low-density lipoprotein cholesterol reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29735484", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 724, "text": "The development of inclisiran, siRNA silencer targeting PCSK9 gene, is a one step forward in these endeavors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850255", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1145, "text": "Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30011788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Inclisiran is a novel drug that inhibits PCSK9 synthesis specifically in the liver, harnessing the natural mechanism of RNAi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30375244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "BACKGROUND\nInclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27959715", "endSection": "abstract" }, { "offsetInBeginSection": 2456, "offsetInEndSection": 2782, "text": "CONCLUSIONS\nInclisiran produces significant and prolonged reductions in atherogenic lipoproteins, suggesting that inhibiting the synthesis of protease proprotein convertase subtilisin/kexin type 9 through siRNA may be a viable alternative to other approaches that target protease proprotein convertase subtilisin/kexin type 9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29735484", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 726, "text": "Inclisiran targets intracellular PCSK9 synthesis specifically, resulting in a dose-dependent, long-term, significant reduction in LDL-C. Inclisiran has been well tolerated and safe, without severe adverse events so far.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 506, "text": "Areas covered: PCSK9 inhibition has emerged as a promising new therapeutic strategy to reduce LDL-C. Inclisiran, a novel, synthetic, siRNA molecule, inhibits PCSK9 synthesis in hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "BACKGROUND\nThe ORION-1 trial (Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol [LDL-C]) demonstrated that inclisiran, an siRNA therapeutic that targets protease proprotein convertase subtilisin/kexin type 9 mRNA within hepatocytes, produces significant low-density lipoprotein cholesterol reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29735484", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 522, "text": "Recently marketed monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown the way towards innovation, while other ways of PCSK9 inhibition like small interfering RNA (Inclisiran) are already being tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29424317", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1287, "text": "Inclisiran inhibits translation of PCSK9 mRNA and thus switches off PCSK9 production and provides advantages over monoclonal antibodies with an infrequent dosing interval of twice a year to reduce LDL-C by over 50%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "endSection": "abstract" }, { "offsetInBeginSection": 955, "offsetInEndSection": 1144, "text": "Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30011788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Inclisiran for the treatment of cardiovascular disease: the ORION clinical development program.Inclisiran is a novel drug that inhibits PCSK9 synthesis specifically in the liver, harnessing the natural mechanism of RNAi. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30375244", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia.The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30011788", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status: The ORION-1 Randomized Clinical Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30487231", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28306389", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 747, "text": "Inclisiran targets intracellular PCSK9 synthesis specifically, resulting in a dose-dependent, long-term, significant reduction in LDL-C. Inclisiran has been well tolerated and safe, without severe adverse events so far.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 859, "text": "This review discusses current PCSK9 inhibitors and the results of phase I and II clinical trials of inclisiran.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 527, "text": "Areas covered: PCSK9 inhibition has emerged as a promising new therapeutic strategy to reduce LDL-C. Inclisiran, a novel, synthetic, siRNA molecule, inhibits PCSK9 synthesis in hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27959715", "endSection": "abstract" } ] }, { "body": "Which tool has been developed for visualization of non-covalent contacts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29335563" ], "ideal_answer": [ "Visualizations of biomolecular structures empower us to gain insights into biological functions, generate testable hypotheses, and communicate biological concepts. Typical visualizations (such as ball and stick) primarily depict covalent bonds. In contrast, non-covalent contacts between atoms, which govern normal physiology, pathogenesis, and drug action, are seldom visualized. The Protein Contacts Atlas has been developed as an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. This resource enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information." ], "exact_answer": [ "Protein Contacts Atlas" ], "type": "factoid", "id": "5c6d65637c78d69471000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Visualization and analysis of non-covalent contacts using the Protein Contacts Atlas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335563", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1052, "text": "Visualizations of biomolecular structures empower us to gain insights into biological functions, generate testable hypotheses, and communicate biological concepts. Typical visualizations (such as ball and stick) primarily depict covalent bonds. In contrast, non-covalent contacts between atoms, which govern normal physiology, pathogenesis, and drug action, are seldom visualized. We present the Protein Contacts Atlas, an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. We developed multiple representations for visualization and analysis of non-covalent contacts at different scales of organization: atoms, residues, secondary structure, subunits, and entire complexes. The Protein Contacts Atlas enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335563", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 1052, "text": "The Protein Contacts Atlas enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335563", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 510, "text": "We present the Protein Contacts Atlas, an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Visualization and analysis of non-covalent contacts using the Protein Contacts Atlas.Visualizations of biomolecular structures empower us to gain insights into biological functions, generate testable hypotheses, and communicate biological concepts. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335563", "endSection": "title" } ] }, { "body": "What is opdivo?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28087644" ], "ideal_answer": [ "Opdivo or nivolumab is a treatment for patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor." ], "type": "summary", "id": "5c910813ecadf2e73f000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "On December 22, 2014, the FDA granted accelerated approval to nivolumab (OPDIVO; Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28087644", "endSection": "abstract" } ] }, { "body": "Has Hesperidin any role as a Neuroprotective Agent?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24987179", "http://www.ncbi.nlm.nih.gov/pubmed/30448580", "http://www.ncbi.nlm.nih.gov/pubmed/28761134", "http://www.ncbi.nlm.nih.gov/pubmed/22850463", "http://www.ncbi.nlm.nih.gov/pubmed/26342684", "http://www.ncbi.nlm.nih.gov/pubmed/24205431", "http://www.ncbi.nlm.nih.gov/pubmed/25860498", "http://www.ncbi.nlm.nih.gov/pubmed/22383310", "http://www.ncbi.nlm.nih.gov/pubmed/21445621", "http://www.ncbi.nlm.nih.gov/pubmed/24211676", "http://www.ncbi.nlm.nih.gov/pubmed/28721824", "http://www.ncbi.nlm.nih.gov/pubmed/29687202", "http://www.ncbi.nlm.nih.gov/pubmed/30352242", "http://www.ncbi.nlm.nih.gov/pubmed/26381129", "http://www.ncbi.nlm.nih.gov/pubmed/16964766", "http://www.ncbi.nlm.nih.gov/pubmed/29136946" ], "ideal_answer": [ "Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease", "Hesperidin has been shown to have a role as a Neuroprotective Agent", "hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury", "Hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury Neuroprotective Effects of Hesperidin on Cerebral Vasospasm" ], "exact_answer": "yes", "type": "yesno", "id": "5c674eac7c78d6947100001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136946", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30352242", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Neuroprotective Effects of Hesperidin on Cerebral Vasospasm", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30448580", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28761134", "endSection": "title" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1830, "text": "This study suggests a potential neuroprotective role of hesperidin against 3-NP-induced Huntington's disease-like manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24987179", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29687202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "PURPOSE\nHesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25860498", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1070, "text": "Hesperidin is a flavonone glycoside, belonging to the flavonoid family, which is widely found in Citrus species and acts as a potent antioxidant and anticancer agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26381129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND\nHesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21445621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26381129", "endSection": "title" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1543, "text": "Our data suggests that hesperidin exerts its neuroprotective effect against rotenone due to its antioxidant, maintenance of mitochondrial function, and antiapoptotic properties in a neuroblastoma cell line.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24205431", "endSection": "abstract" }, { "offsetInBeginSection": 1317, "offsetInEndSection": 1552, "text": "Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16964766", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 384, "text": "The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation.We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28761134", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease.Rotenone a widely used pesticide that inhibits mitochondrial complex I has been used to investigate the pathobiology of PD both in vitro and in vivo. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24205431", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Cytoprotective effects of hesperetin and hesperidin against amyloid \u03b2-induced impairment of glucose transport through downregulation of neuronal autophagy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383310", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.Hesp possesses potent anticonvulsant activity which might be mediated through modulation of gamma-amino butyric acid/benzodiazepine receptor action.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24987179", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin.The present study evaluated antioxidant and neuroprotective activities of hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone hesperetin using cell-free bioassay system and primary cultured rat cortical cells. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16964766", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22850463", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26342684", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24211676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Potential anti-inflammatory effects of hesperidin from the genus Citrus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28721824", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16964766", "endSection": "title" }, { "offsetInBeginSection": 739, "offsetInEndSection": 899, "text": "Hesperidin is a flavonoid present in high concentration in citrus species and has numerous biological properties, principally antioxidant and anti-inflammatory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28721824", "endSection": "abstract" } ] }, { "body": "Are apoE mimetics being considered as a treatment against Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22965147" ], "ideal_answer": [ "Yes, apoE mimetics are being considered as a treatment against Alzheimer's disease, and they have been shown to protect AD mouse models against these AD-like features." ], "exact_answer": "yes", "type": "yesno", "id": "5c8857e975a4a5d219000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22965147", "endSection": "title" }, { "offsetInBeginSection": 316, "offsetInEndSection": 471, "text": "Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22965147", "endSection": "abstract" } ] }, { "body": "Which diseases are treated with netarsudil?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29199013", "http://www.ncbi.nlm.nih.gov/pubmed/28609185", "http://www.ncbi.nlm.nih.gov/pubmed/30323550", "http://www.ncbi.nlm.nih.gov/pubmed/27072905", "http://www.ncbi.nlm.nih.gov/pubmed/29469601", "http://www.ncbi.nlm.nih.gov/pubmed/30007591", "http://www.ncbi.nlm.nih.gov/pubmed/29622939", "http://www.ncbi.nlm.nih.gov/pubmed/30209441", "http://www.ncbi.nlm.nih.gov/pubmed/30028313", "http://www.ncbi.nlm.nih.gov/pubmed/29453668" ], "ideal_answer": [ "In 2 large, randomized, double-masked trials, once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma." ], "exact_answer": [ [ "ocular hypertension" ], [ "open-angle glaucoma" ] ], "type": "list", "id": "5c73ad0f7c78d69471000096", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase\u00a0Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199013", "endSection": "title" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1685, "text": "CONCLUSIONS: In 2 large, randomized, double-masked trials reported here, once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 439, "text": "Netarsudil ophthalmic solution 0.02% (hereafter referred to as netarsudil 0.02%) [Rhopressa\u00ae] is a Rho-associated protein kinase inhibitor that is thought to lower intraocular pressure (IOP) by increasing aqueous humour outflow through the trabecular meshwork. It has been developed by Aerie Pharmaceuticals and was recently approved in the USA for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29453668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "PURPOSE: Netarsudil, an inhibitor of Rho kinase and a norepinephrine transporter, has been shown to lower elevated intraocular pressure (IOP) in controlled studies of patients with open-angle glaucoma and ocular hypertension, and in healthy volunteers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29469601", "endSection": "abstract" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1648, "text": "CONCLUSIONS: Once-daily dosing of netarsudil ophthalmic solution 0.02% lowered IOP through increasing trabecular outflow facility and reducing EVP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29469601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Netarsudil ophthalmic solution (Rhopressa) for the reduction of elevated intraocular pressure; ertugliflozin (Steglatro) for adults with type-2 diabetes; and lutetium lu 177 dotatate (Lutathera) for certain gastroenteropancreatic neuroendocrine tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29622939", "endSection": "abstract" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1452, "text": "Two recently approved multi-pharmacophoric drugs (e.g., rho kinase inhibitor, Netarsudil; a drug conjugate, Latanoprostene Bunod) and novel aqueous humor drainage devices (iStent and CyPass) are also gaining acceptance for treating POAG/ NTG. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30028313", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 764, "text": "Ultimately, a search for Rho kinase inhibitors led to the discovery of several molecules of therapeutic interest, leaving us today with 2 new ocular hypotensive agents approved for clinical use: ripasudil in Japan and netarsudil in the United States. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30007591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Netarsudil ophthalmic solution 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30209441", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Once-daily (p.m.) netarsudil ophthalmic solution 0.02% (Rhopressa) is approved in the United States for lowering elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30209441", "endSection": "abstract" }, { "offsetInBeginSection": 1457, "offsetInEndSection": 1691, "text": "CONCLUSIONS\nIn 2 large, randomized, double-masked trials reported here, once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28609185", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Netarsudil ophthalmic solution is a novel topical intraocular pressure (IOP)-lowering agent that has recently been approved by the US Food and Drug Administration (FDA) for the treatment of ocular hypertension and open-angle glaucoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Once-daily (p.m.) netarsudil ophthalmic solution 0.02% (Rhopressa) is approved in the United States for lowering elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30209441", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 796, "text": "This article summarizes the milestones in the development of netarsudil 0.02% leading to this first approval for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29453668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27072905", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 352, "text": "Profile of netarsudil ophthalmic solution and its potential in the treatment of open-angle glaucoma: evidence to date.Netarsudil ophthalmic solution is a novel topical intraocular pressure (IOP)-lowering agent that has recently been approved by the US Food and Drug Administration (FDA) for the treatment of ocular hypertension and open-angle glaucoma. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323550", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma.Netarsudil is a novel ROCK/NET inhibitor with high potency in biochemical and cell-based assays, an ability to produce large and durable IOP reductions in animal models, and favorable pharmacokinetic and ocular tolerability profiles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28609185", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Profile of netarsudil ophthalmic solution and its potential in the treatment of open-angle glaucoma: evidence to date.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323550", "endSection": "title" }, { "offsetInBeginSection": 1427, "offsetInEndSection": 1649, "text": "In 2 large, randomized, double-masked trials reported here, once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "To evaluate the efficacy and ocular and systemic safety of netarsudil 0.02% ophthalmic solution, a rho-kinase inhibitor and norepinephrine transporter inhibitor, in patients with open-angle glaucoma and ocular hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199013", "endSection": "abstract" } ] }, { "body": "Can you computationally predict Molecular Recognition Features (MoRFs) regions in Intrinsically Disordered Proteins (IDPs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30324701", "http://www.ncbi.nlm.nih.gov/pubmed/30298407", "http://www.ncbi.nlm.nih.gov/pubmed/25637562", "http://www.ncbi.nlm.nih.gov/pubmed/26517836", "http://www.ncbi.nlm.nih.gov/pubmed/29360926", "http://www.ncbi.nlm.nih.gov/pubmed/29042212" ], "ideal_answer": [ "Yes. There are various tools available in the literature that enable computational identification of Molecular Recognition Features (MoRFs) regions in intrinsically disordered protein sequences." ], "exact_answer": "yes", "type": "yesno", "id": "5c6d9a157c78d69471000041", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Predicting Functions of Disordered Proteins with MoRFpred.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30298407", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 949, "text": "Intrinsically disordered proteins and regions are involved in a wide range of cellular functions, and they often facilitate protein-protein interactions. Molecular recognition features (MoRFs) are segments of intrinsically disordered regions that bind to partner proteins, where binding is concomitant with a transition to a structured conformation. MoRFs facilitate translation, transport, signaling, and regulatory processes and are found across all domains of life. A popular computational tool, MoRFpred, accurately predicts MoRFs in protein sequences. MoRFpred is implemented as a user-friendly web server that is freely available at http://biomine.cs.vcu.edu/servers/MoRFpred/ . We describe this predictor, explain how to run the web server, and show how to interpret the results it generates. We also demonstrate the utility of this web server based on two case studies, focusing on the relevance of evolutionary conservation of MoRF regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30298407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "MoRFPred-plus: Computational Identification of MoRFs in Protein Sequences using Physicochemical Properties and HMM profiles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29042212", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1777, "text": "Intrinsically Disordered Proteins (IDPs) lack stable tertiary structure and they actively participate in performing various biological functions. These IDPs expose short binding regions called Molecular Recognition Features (MoRFs) that permit interaction with structured protein regions. Upon interaction they undergo a disorder-to-order transition as a result of which their functionality arises. Predicting these MoRFs in disordered protein sequences is a challenging task.METHOD: In this study, we present MoRFpred-plus, an improved predictor over our previous proposed predictor to identify MoRFs in disordered protein sequences. Two separate independent propensity scores are computed via incorporating physicochemical properties and HMM profiles, these scores are combined to predict final MoRF propensity score for a given residue. The first score reflects the characteristics of a query residue to be part of MoRF region based on the composition and similarity of assumed MoRF and flank regions. The second score reflects the characteristics of a query residue to be part of MoRF region based on the properties of flanks associated around the given residue in the query protein sequence. The propensity scores are processed and common averaging is applied to generate the final prediction score of MoRFpred-plus.RESULTS: Performance of the proposed predictor is compared with available MoRF predictors, MoRFchibi, MoRFpred, and ANCHOR. Using previously collected training and test sets used to evaluate the mentioned predictors, the proposed predictor outperforms these predictors and generates lower false positive rate. In addition, MoRFpred-plus is a downloadable predictor, which makes it useful as it can be used as input to other computational tools.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29042212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "OPAL: prediction of MoRF regions in intrinsically disordered protein sequences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29360926", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1433, "text": "Intrinsically disordered proteins lack stable 3-dimensional structure and play a crucial role in performing various biological functions. Key to their biological function are the molecular recognition features (MoRFs) located within long disordered regions. Computationally identifying these MoRFs from disordered protein sequences is a challenging task. In this study, we present a new MoRF predictor, OPAL, to identify MoRFs in disordered protein sequences. OPAL utilizes two independent sources of information computed using different component predictors. The scores are processed and combined using common averaging method. The first score is computed using a component MoRF predictor which utilizes composition and sequence similarity of MoRF and non-MoRF regions to detect MoRFs. The second score is calculated using half-sphere exposure (HSE), solvent accessible surface area (ASA) and backbone angle information of the disordered protein sequence, using information from the amino acid properties of flanks surrounding the MoRFs to distinguish MoRF and non-MoRF residues.Results: OPAL is evaluated using test sets that were previously used to evaluate MoRF predictors, MoRFpred, MoRFchibi and MoRFchibi-web. The results demonstrate that OPAL outperforms all the available MoRF predictors and is the most accurate predictor available for MoRF prediction. It is available at http://www.alok-ai-lab.com/tools/opal/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29360926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "OPAL+: Length-Specific MoRF Prediction in Intrinsically Disordered Protein Sequences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30324701", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 972, "text": "Intrinsically disordered proteins (IDPs) contain long unstructured regions, which play an important role in their function. These intrinsically disordered regions (IDRs) participate in binding events through regions called molecular recognition features (MoRFs). Computational prediction of MoRFs helps identify the potentially functional regions in IDRs. In this study, OPAL+, a novel MoRF predictor, is presented. OPAL+ uses separate models to predict MoRFs of varying lengths along with incorporating the hidden Markov model (HMM) profiles and physicochemical properties of MoRFs and their flanking regions. Together, these features help OPAL+ achieve a marginal performance improvement of 0.4-0.7% over its predecessor for diverse MoRF test sets. This performance improvement comes at the expense of increased run time as a result of the requirement of HMM profiles. OPAL+ is available for download at https://github.com/roneshsharma/OPAL-plus/wiki/OPAL-plus-Download.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30324701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26517836", "endSection": "title" }, { "offsetInBeginSection": 131, "offsetInEndSection": 1810, "text": "Key to their regulatory function is often the binding to globular protein domains via sequence elements known as molecular recognition features (MoRFs). Development of computational tools for the identification of candidate MoRF locations in amino acid sequences is an important task and an area of growing interest. Given the relative sparseness of MoRFs in protein sequences, the accuracy of the available MoRF predictors is often inadequate for practical usage, which leaves a significant need and room for improvement. In this work, we introduce MoRFCHiBi_Web, which predicts MoRF locations in protein sequences with higher accuracy compared to current MoRF predictors.METHODS: Three distinct and largely independent property scores are computed with component predictors and then combined to generate the final MoRF propensity scores. The first score reflects the likelihood of sequence windows to harbour MoRFs and is based on amino acid composition and sequence similarity information. It is generated by MoRFCHiBi using small windows of up to 40 residues in size. The second score identifies long stretches of protein disorder and is generated by ESpritz with the DisProt option. Lastly, the third score reflects residue conservation and is assembled from PSSM files generated by PSI-BLAST. These propensity scores are processed and then hierarchically combined using Bayes rule to generate the final MoRFCHiBi_Web predictions.RESULTS: MoRFCHiBi_Web was tested on three datasets. Results show that MoRFCHiBi_Web outperforms previously developed predictors by generating less than half the false positive rate for the same true positive rate at practical threshold values.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26517836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Computational identification of MoRFs in protein sequences.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25637562", "endSection": "title" }, { "offsetInBeginSection": 429, "offsetInEndSection": 1580, "text": "In this study, we introduce MoRFCHiBi, a new computational approach for fast and accurate prediction of MoRFs in protein sequences. MoRFCHiBi combines the outcomes of two support vector machine (SVM) models that take advantage of two different kernels with high noise tolerance. The first, SVMS, is designed to extract maximal information from the general contrast in amino acid compositions between MoRFs, their surrounding regions (Flanks), and the remainders of the sequences. The second, SVMT, is used to identify similarities between regions in a query sequence and MoRFs of the training set.RESULTS: We evaluated the performance of our predictor by comparing its results with those of two currently available MoRF predictors, MoRFpred and ANCHOR. Using three test sets that have previously been collected and used to evaluate MoRFpred and ANCHOR, we demonstrate that MoRFCHiBi outperforms the other predictors with respect to different evaluation metrics. In addition, MoRFCHiBi is downloadable and fast, which makes it useful as a component in other computational prediction tools.AVAILABILITY AND IMPLEMENTATION: http://www.chibi.ubc.ca/morf/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25637562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OPAL: prediction of MoRF regions in intrinsically disordered protein sequences.Supplementary data are available at Bioinformatics online.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29360926", "endSection": "title" }, { "offsetInBeginSection": 263, "offsetInEndSection": 355, "text": "Computational prediction of MoRFs helps identify the potentially functional regions in IDRs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30324701", "endSection": "abstract" } ] }, { "body": "Which malignancies is Keytruda approved for before 2017?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29209918" ], "ideal_answer": [ "Before 2017 Keytruda was approved for the treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma." ], "exact_answer": [ [ "metastatic melanoma" ], [ "metastatic non-small cell lung cancer" ], [ "recurrent or metastatic head and neck cancer" ], [ "refractory Hodgkin lymphoma" ], [ "urothelial carcinoma" ] ], "type": "list", "id": "5c9158a5ecadf2e73f000008", "snippets": [ { "offsetInBeginSection": 335, "offsetInEndSection": 669, "text": "FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29209918", "endSection": "abstract" } ] }, { "body": "Which was the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29209918" ], "ideal_answer": [ "The first approved tumor treatment using a common biomarker rather than specified tumor locations in the body was Keytruda, which is a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers." ], "exact_answer": [ "Keytruda" ], "type": "factoid", "id": "5c915a8becadf2e73f000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29209918", "endSection": "abstract" } ] }, { "body": "What does Prevnar 13 consist of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26242768" ], "ideal_answer": [ "Prevnar 13 consists of 13 serotype-specific polysaccharides of Streptococcus pneumoniae (pneumococcus), each covalently conjugated to a non-toxic immunogenic carrier protein." ], "type": "summary", "id": "5c915ca7ecadf2e73f00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The 13-valent pneumococcal conjugate vaccine (Prevenar 13(\u00ae), Prevnar 13(\u00ae)) [PCV13] consists of 13 serotype-specific polysaccharides of Streptococcus pneumoniae (pneumococcus), each covalently conjugated to a non-toxic immunogenic carrier protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26242768", "endSection": "abstract" } ] }, { "body": "What is the route of administration of apixaban?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27653758" ], "ideal_answer": [ "Apixaban is administered orally." ], "exact_answer": [ "Oral" ], "type": "factoid", "id": "5c920df7ecadf2e73f00000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 834, "text": "Apixaban (Eliquis\u00ae) is an oral, direct factor Xa inhibitor that is available for use in the treatment and secondary prevention of venous thromboembolism (VTE). Like other direct oral anticoagulants (DOACs), apixaban has generally predictable pharmacological properties and does not require routine anticoagulation monitoring. In large phase III trials, oral apixaban was noninferior to subcutaneous enoxaparin sodium overlapped with and followed by oral warfarin (enoxaparin/warfarin) in the treatment of adults with acute VTE over 6\u00a0months with regard to the incidence of recurrent VTE or VTE-related death (AMPLIFY), and was significantly more effective than placebo in the prevention of recurrent VTE or all-cause mortality over 12\u00a0months in patients who had completed 6-12\u00a0months' anticoagulation treatment for VTE (AMPLIFY-EXT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27653758", "endSection": "abstract" } ] }, { "body": "What is the cause of a STAG3 truncating variant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27836978", "http://www.ncbi.nlm.nih.gov/pubmed/26059840", "http://www.ncbi.nlm.nih.gov/pubmed/30006057" ], "ideal_answer": [ "Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family", "Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family." ], "exact_answer": [ "Primary ovarian insufficiency", "POI" ], "type": "factoid", "id": "5c632cc1e842deac6700000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "STAG3 truncating variant as the cause of primary ovarian insufficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059840", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1233, "text": "Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Our objective was to determine the genetic cause of POI in a consanguineous Lebanese family with two affected sisters presenting with primary amenorrhoea and an absence of any pubertal development. Multipoint parametric linkage analysis was performed. Whole-exome sequencing was done on the proband. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family. Exome sequencing combined with linkage analyses offers a powerful tool to efficiently find novel genetic causes of rare, heterogeneous disorders, even in small single families. This is only the second report of a STAG3 variant; the first STAG3 variant was recently described in a phenotypically similar family with extreme POI. Identification of an additional family highlights the importance of STAG3 in POI pathogenesis and suggests it should be evaluated in families affected with POI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "STAG3 truncating variant as the cause of primary ovarian insufficiency.Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26059840", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Two rare loss-of-function variants in the STAG3 gene leading to primary ovarian insufficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006057", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "A homozygous NOBOX truncating variant causes defective transcriptional activation and leads to primary ovarian insufficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27836978", "endSection": "title" }, { "offsetInBeginSection": 1270, "offsetInEndSection": 1556, "text": "The parents' DNA was not available to segregate these variants.
CONCLUSION: Our results suggested that POI is caused by pathogenic compound heterozygous variants in the STAG3 gene, supporting the key role of the STAG3 gene in the etiology of primary ovarian insufficiency.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006057", "endSection": "abstract" }, { "offsetInBeginSection": 1410, "offsetInEndSection": 1606, "text": "Our results suggested that POI is caused by pathogenic compound heterozygous variants in the STAG3 gene, supporting the key role of the STAG3 gene in the etiology of primary ovarian insufficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30006057", "endSection": "abstract" } ] }, { "body": "Which tools have been developed for computing split-networks?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29186450", "http://www.ncbi.nlm.nih.gov/pubmed/24436254", "http://www.ncbi.nlm.nih.gov/pubmed/17119010" ], "ideal_answer": [ "Split-networks are a generalization of phylogenetic trees that have proven to be a powerful tool in phylogenetics. Tools for computing such networks include SPECTRE, FlatNJ and QNet." ], "exact_answer": [ [ "SPECTRE" ], [ "FlatNJ" ], [ "QNet" ] ], "type": "list", "id": "5c6c497d7c78d69471000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "SPECTRE: a suite of phylogenetic tools for reticulate evolution.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29186450", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1019, "text": "Split-networks are a generalization of phylogenetic trees that have proven to be a powerful tool in phylogenetics. Various ways have been developed for computing such networks, including split-decomposition, NeighborNet, QNet and FlatNJ. Some of these approaches are implemented in the user-friendly SplitsTree software package. However, to give the user the option to adjust and extend these approaches and to facilitate their integration into analysis pipelines, there is a need for robust, open-source implementations of associated data structures and algorithms. Here, we present SPECTRE, a readily available, open-source library of data structures written in Java, that comes complete with new implementations of several pre-published algorithms and a basic interactive graphical interface for visualizing planar split networks. SPECTRE also supports the use of longer running algorithms by providing command line interfaces, which can be executed on servers or in High Performance Computing environments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29186450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "FlatNJ: a novel network-based approach to visualize evolutionary and biogeographical relationships.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24436254", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Split networks are a type of phylogenetic network that allow visualization of conflict in evolutionary data. We present a new method for constructing such networks called FlatNetJoining (FlatNJ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24436254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "QNet: an agglomerative method for the construction of phylogenetic networks from weighted quartets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119010", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "We present QNet, a method for constructing split networks from weighted quartet trees. QNet can be viewed as a quartet analogue of the distance-based Neighbor-Net (NNet) method for network construction. Just as NNet, QNet works by agglomeratively computing a collection of circular weighted splits of the taxa set which is subsequently represented by a planar split network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119010", "endSection": "abstract" } ] }, { "body": "List 3 apoE mimetics.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22149316", "http://www.ncbi.nlm.nih.gov/pubmed/16740622" ], "ideal_answer": [ "COG133, COG112 and Ac-hE18A-NH(2) are apoE mimetics." ], "exact_answer": [ [ "COG133" ], [ "COG112" ], [ "Ac-hE18A-NH(2)" ] ], "type": "list", "id": "5c88550075a4a5d219000008", "snippets": [ { "offsetInBeginSection": 428, "offsetInEndSection": 1018, "text": "Using a murine experimental autoimmune encephalomyelitis (EAE) model of human multiple sclerosis, we found that a peptidomimetic of apoE protein, COG133, substantially reduces the clinical symptoms of EAE and promotes remission from the disability when administered before or after onset of disease. Most notably, fusion of COG133 to a protein transduction domain creates COG112, a modified apoE-mimetic peptide with significantly enhanced anti-inflammatory bioactivities in vitro, and improved therapeutic effects on EAE in vivo, which renders a nearly full remission from the disability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16740622", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 688, "text": "Toward this end, we describe the design and studies of a dual-domain apoE mimetic peptide, Ac-hE18A-NH(2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22149316", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1570, "text": "ApoE mimetics such as Ac-hE18A-NH(2) may therefore restore or replace ligands in genetically induced hyperlipidemias to enable reduction in atherogenic lipoproteins via HSPG even in the absence of functional low-density lipoprotein receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22149316", "endSection": "abstract" } ] }, { "body": "What are there sex differences in SAMHD1 activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30299483" ], "ideal_answer": [ "The host restriction factor SAMHD1 exists in a hyperphosphorylated, less active state in male-derived macrophages. SAMHD1 is an essential modulator of infectivity in a sex-dependent manner in macrophages, constituting a novel component of sex differences in innate immune control of HIV-1." ], "type": "summary", "id": "5c93ea7cecadf2e73f00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Sex influences SAMHD1 activity and susceptibility to HIV-1 in primary human macrophages.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30299483", "endSection": "title" }, { "offsetInBeginSection": 717, "offsetInEndSection": 1387, "text": "Investigations into the mechanism governing these sex-dependent differences revealed that the host restriction factor SAMHD1 exists in a hyperphosphorylated, less active state in male-derived macrophages. In addition, the major kinase responsible for SAMHD1 phosphorylation, CDK1, exhibited lower levels of expression in female-derived macrophages in all tested donor pairs. The sex-dependent differences in viral restriction imposed by SAMHD1 were abrogated upon its depletion. We conclude that SAMHD1 is an essential modulator of infectivity in a sex-dependent manner in macrophages, constituting a novel component of sex differences in innate immune control of HIV-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30299483", "endSection": "abstract" } ] }, { "body": "Which enhancers are characterized as latent?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23332752" ], "ideal_answer": [ "Here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation.", "Latent enhancers are defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation.", "Here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by TFs", "here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by tfs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation.", "Here , we describe latent enhancers , defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation ." ], "type": "summary", "id": "5ca60a77ecadf2e73f00004d", "snippets": [ { "offsetInBeginSection": 368, "offsetInEndSection": 606, "text": "Here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332752", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 605, "text": "Here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Latent enhancers activated by stimulation in differentiated cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332752", "endSection": "title" } ] }, { "body": "What is the difference between COG133 and COG112?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16740622" ], "ideal_answer": [ "COG112 results from the fusion of COG133 to a protein transduction domain." ], "type": "summary", "id": "5c88b8a275a4a5d21900000b", "snippets": [ { "offsetInBeginSection": 728, "offsetInEndSection": 1017, "text": "Most notably, fusion of COG133 to a protein transduction domain creates COG112, a modified apoE-mimetic peptide with significantly enhanced anti-inflammatory bioactivities in vitro, and improved therapeutic effects on EAE in vivo, which renders a nearly full remission from the disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16740622", "endSection": "abstract" } ] }, { "body": "Velocardial facial syndrome, otherwise known as Di George syndrome is caused by a deletion in chromosome 21, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9674897", "http://www.ncbi.nlm.nih.gov/pubmed/26605035", "http://www.ncbi.nlm.nih.gov/pubmed/16617304", "http://www.ncbi.nlm.nih.gov/pubmed/15734119", "http://www.ncbi.nlm.nih.gov/pubmed/8998528", "http://www.ncbi.nlm.nih.gov/pubmed/25523123", "http://www.ncbi.nlm.nih.gov/pubmed/12238021" ], "ideal_answer": [ "Velocardial facial syndrome, otherwise known as Di George syndrome is caused by a deletion in chromosome 22.", "The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome." ], "exact_answer": "no", "type": "yesno", "id": "5c97a08becadf2e73f000029", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 117, "text": "The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15734119", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 451, "text": "deletions of chromosome 7q11.23 (Williams syndrome), 15q11-q13 (Angelman syndrome, Prader-Willi syndrome) and 22q11 (Di George syndrome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16617304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9674897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The 22q11.2 deletion syndrome (di George syndrome) is one of the most prevalent genetic disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26605035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "UNLABELLED\nMost of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8998528", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9674897", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 364, "text": "22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25523123", "endSection": "abstract" }, { "offsetInBeginSection": 1088, "offsetInEndSection": 1580, "text": "Di George syndrome due to mutation on 22q or 10q) and can also result from microdeletion or point mutation (in the Shprintzen syndrome 70% represent microdeletion and 30% point mutation at 22q11, in Rubinstein-Taybi syndrome 10% cases result from microdeletions and 90% from point mutations); 7) Population incidence of microdeletions is high (1:4000 to 1:30,000) because their etiologic mechanism is related to the common unequal crossing over; 8) Imprinting plays a role in some cases, e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12238021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "[Microdeletion of the chromosome 22q11 in children: apropos of a series of 49 patients].Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8998528", "endSection": "title" }, { "offsetInBeginSection": 236, "offsetInEndSection": 488, "text": "22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25523123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "UNLABELLED: Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8998528", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8998528", "endSection": "abstract" } ] }, { "body": "Is the protein Asporin related to disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25689697", "http://www.ncbi.nlm.nih.gov/pubmed/27409832", "http://www.ncbi.nlm.nih.gov/pubmed/28152543", "http://www.ncbi.nlm.nih.gov/pubmed/27705916" ], "ideal_answer": [ "Yes,\nAccumulating evidence demonstrates the involvement of asporin in OA pathogenesis. Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5c8ab614d558e5f23200000d", "snippets": [ { "offsetInBeginSection": 307, "offsetInEndSection": 388, "text": "Accumulating evidence demonstrates the involvement of asporin in OA pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25689697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27409832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Asporin has been implicated as an oncogene in various types of human cancers; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27705916", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1425, "text": " These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27705916", "endSection": "abstract" }, { "offsetInBeginSection": 1975, "offsetInEndSection": 2118, "text": "Our results suggest that ASPN is a stromally expressed biomarker that correlates with disease progression, and is observed in reactive stroma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28152543", "endSection": "abstract" } ] }, { "body": "Can TAD disruption lead to disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27111891", "http://www.ncbi.nlm.nih.gov/pubmed/28408976", "http://www.ncbi.nlm.nih.gov/pubmed/30086749", "http://www.ncbi.nlm.nih.gov/pubmed/29990539", "http://www.ncbi.nlm.nih.gov/pubmed/30241613", "http://www.ncbi.nlm.nih.gov/pubmed/30374058", "http://www.ncbi.nlm.nih.gov/pubmed/26862051", "http://www.ncbi.nlm.nih.gov/pubmed/22495304", "http://www.ncbi.nlm.nih.gov/pubmed/25959774" ], "ideal_answer": [ "TAD boundaries are insulators of genomic neighborhoods. \u03a4he disruption of these structures by genomic rearrangements can result in gene misexpression and disease.", "We discuss how the disruption of these structures by genomic rearrangements can result in gene misexpression and disease." ], "exact_answer": "yes", "type": "yesno", "id": "5ca61176ecadf2e73f00004e", "snippets": [ { "offsetInBeginSection": 695, "offsetInEndSection": 954, "text": "its perturbation will lead to human disease, highlighting the accumulating evidence that links the diverse 3D genome architecture components to a multitude of human diseases and the emerging mechanisms by which 3D genome derangement causes disease phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29990539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "TAD boundaries are insulators of genomic neighborhoods. In this issue, Sun et\u00a0al. show that disease-associated tandem repeats are located to TAD boundaries and affect their insulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30241613", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 773, "text": "Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28408976", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 941, "text": "Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28408976", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 546, "text": "the disruption of these structures by genomic rearrangements can result in gene misexpression and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26862051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 35, "text": "TAD disruption as oncogenic driver.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27111891", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 409, "text": "Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27111891", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 277, "text": "Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27111891", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 625, "text": "However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30086749", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 409, "text": "Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30374058", "endSection": "abstract" }, { "offsetInBeginSection": 349, "offsetInEndSection": 456, "text": "Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30086749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Deletion in 2q35 excluding the IHH gene leads to fetal severe limb anomalies and suggests a disruption of chromatin architecture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30374058", "endSection": "title" }, { "offsetInBeginSection": 194, "offsetInEndSection": 315, "text": "We demonstrate that disruption of TADs can rewire long-range regulatory architecture and result in pathogenic phenotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25959774", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 312, "text": "Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27111891", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 583, "text": "Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30086749", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1187, "text": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22495304", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 854, "text": "Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28408976", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 444, "text": "Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27111891", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 538, "text": "Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30374058", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1021, "text": "Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28408976", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 752, "text": "However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30086749", "endSection": "abstract" } ] }, { "body": "Is L-4F an apoE mimetic peptide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29245934" ], "ideal_answer": [ "No, L-4F is an apoA-I mimetic peptide." ], "exact_answer": "no", "type": "yesno", "id": "5c8908a475a4a5d21900000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29245934", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 337, "text": "L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29245934", "endSection": "abstract" } ] }, { "body": "Which cells secrete lactotransferrin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24561791" ], "ideal_answer": [ "We conclude that lactotransferrin represents a late stage differentiation marker of neutrophils, macrophages and distinct subtypes of dendritic cells." ], "exact_answer": [ [ "neutrophils" ], [ "macrophages" ], [ "dendritic" ] ], "type": "list", "id": "5c8c095e0101eac870000002", "snippets": [ { "offsetInBeginSection": 1243, "offsetInEndSection": 1393, "text": "We conclude that lactotransferrin represents a late stage differentiation marker of neutrophils, macrophages and distinct subtypes of dendritic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24561791", "endSection": "abstract" } ] }, { "body": "Which plant does oleuropein originate from?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29099642" ], "ideal_answer": [ "Oleuropein originates from olive trees, and is specifically found in olive leaf extracts." ], "exact_answer": [ "Olive tree" ], "type": "factoid", "id": "5c890ad575a4a5d21900000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Oleuropein Is Responsible for the Major Anti-Inflammatory Effects of Olive Leaf Extract.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29099642", "endSection": "title" }, { "offsetInBeginSection": 745, "offsetInEndSection": 854, "text": "Oleuropein is the only OLE component that has shown anti-inflammatory effects at a concentration of 20\u2009\u03bcg/mL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29099642", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1242, "text": "Downregulation of TNF\u03b1 secretion in PMNCs culture in response to OLE treatment indicates that this polyphenol-rich extract has an anti-inflammatory effect, and oleuropein is the major OLE component responsible for this effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29099642", "endSection": "abstract" } ] }, { "body": "Reslizumab is a humanized monoclonal antibody to treat what specific type of asthma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29554826", "http://www.ncbi.nlm.nih.gov/pubmed/29059618", "http://www.ncbi.nlm.nih.gov/pubmed/30346831", "http://www.ncbi.nlm.nih.gov/pubmed/27458609", "http://www.ncbi.nlm.nih.gov/pubmed/27445482", "http://www.ncbi.nlm.nih.gov/pubmed/28683596", "http://www.ncbi.nlm.nih.gov/pubmed/28344579", "http://www.ncbi.nlm.nih.gov/pubmed/29486600", "http://www.ncbi.nlm.nih.gov/pubmed/28421429", "http://www.ncbi.nlm.nih.gov/pubmed/23326187" ], "ideal_answer": [ "Reslizumab in the treatment of severe eosinophilic asthma:\u00a0an update.", "Reslizumab is a humanized monoclonal antibody to treat eosinophilic asthma" ], "exact_answer": [ "eosinophilic asthma" ], "type": "factoid", "id": "5ca0bf00ecadf2e73f000045", "snippets": [ { "offsetInBeginSection": 131, "offsetInEndSection": 398, "text": "Since IL-5 plays an important role in the maturation, survival and migration of eosinophils, hence the pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5R\u03b1 have been developed and/or marketed, including Mepolizumab, Reslizumab, and Benralizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29059618", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 383, "text": "Reslizumab, a humanized mAb against IL-5, reduces the number of eosinophils in the blood and lungs. Based on efficacy and safety data from pivotal RCTs, reslizumab had been approved for use as an add-on maintenance treatment of severe asthma with an eosinophilic phenotype in adults who have a history of exacerbations despite receiving their current asthma medicines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29486600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Reslizumab in the treatment of severe eosinophilic asthma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554826", "endSection": "title" }, { "offsetInBeginSection": 311, "offsetInEndSection": 547, "text": "Reslizumab is a humanized monoclonal (immunoglobulin G4/\u03ba) antibody that binds with high affinity to circulating human IL-5 and downregulates the IL-5 signaling pathway, potentially disrupting the maturation and survival of eosinophils.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Reslizumab (Cinqaero\u00ae; Cinqair\u00ae) is a humanized monoclonal antibody against interleukin-5 (IL-5), a cytokine mediator of eosinophilic airway inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28421429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "BACKGROUND\nReslizumab is a humanized anti-interleukin-5 monoclonal antibody used as add-on maintenance treatment for patients with uncontrolled eosinophilic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346831", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 920, "text": "In particular, reslizumab is a humanized anti-IL-5 monoclonal antibody that has been found to be an effective and safe add-on therapy, capable of decreasing asthma exacerbations and significantly improving disease control and lung function in patients experiencing persistent allergic or nonallergic eosinophilic asthma, despite the regular use of moderate-to-high doses of inhaled corticosteroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27445482", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 483, "text": "Reslizumab (Cinquil\u2122) is a humanized monoclonal antibody with potent interleukin-5 neutralizing effects, which represents a potential treatment for poorly controlled eosinophilic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326187", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 316, "text": "Reslizumab is indicated as an add-on treatment for severe eosinophilic asthma in adults, on the basis of data from the BREATH phase III clinical trial programme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28421429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Reslizumab in Eosinophilic Asthma: A Review.Reslizumab (Cinqaero\u00ae; Cinqair\u00ae) is a humanized monoclonal antibody against interleukin-5 (IL-5), a cytokine mediator of eosinophilic airway inflammation. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28421429", "endSection": "title" }, { "offsetInBeginSection": 477, "offsetInEndSection": 713, "text": "Reslizumab is a humanized monoclonal (immunoglobulin G4/\u03ba) antibody that binds with high affinity to circulating human IL-5 and downregulates the IL-5 signaling pathway, potentially disrupting the maturation and survival of eosinophils. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28683596", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 605, "text": "Reslizumab (Cinquil\u2122) is a humanized monoclonal antibody with potent interleukin-5 neutralizing effects, which represents a potential treatment for poorly controlled eosinophilic asthma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Reslizumab: Maintenance treatment for eosinophilic asthma inadequately controlled on corticosteroids.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458609", "endSection": "title" } ] }, { "body": "What is the function of the protein Magt1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30385806", "http://www.ncbi.nlm.nih.gov/pubmed/29581357", "http://www.ncbi.nlm.nih.gov/pubmed/29051561" ], "ideal_answer": [ "The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium ([Mg2+]i) levels." ], "exact_answer": [ "Magnesium transporter" ], "type": "factoid", "id": "5c92869aecadf2e73f000015", "snippets": [ { "offsetInBeginSection": 162, "offsetInEndSection": 193, "text": "magnesium transporter 1 (MAGT1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29581357", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 244, "text": "magnesium transporter MagT1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30385806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium ([Mg2+]i) levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29051561", "endSection": "abstract" } ] }, { "body": "Can oleuropein aglycone interfere with amyloid aggregation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29571746" ], "ideal_answer": [ "Yes, oleuropein aglycone interferes in vitro and in vivo with amyloid aggregates." ], "exact_answer": "yes", "type": "yesno", "id": "5c890c3375a4a5d21900000e", "snippets": [ { "offsetInBeginSection": 285, "offsetInEndSection": 684, "text": "Oleuropein, a phenolic secoiroid glycoside, is the main polyphenol in the olive oil. It has been reported that the aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid aggregation of a number of proteins/peptides involved in amyloid, particularly neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying protection against cognitive deterioration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571746", "endSection": "abstract" } ] }, { "body": "What is the function of the transcriptional co-activator p300?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23211718", "http://www.ncbi.nlm.nih.gov/pubmed/30323286" ], "ideal_answer": [ "The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin." ], "exact_answer": [ "histone acetyltransferase" ], "type": "factoid", "id": "5c990241ecadf2e73f00002d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "p300, a transcriptional co-activator with histone acetyl transferase (HAT) activity, plays an essential role in the pathogenesis of cardiomyocyte hypertrophy in response to multiple pro-hypertrophic stimuli including hyperglycemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23211718", "endSection": "abstract" } ] }, { "body": "What is another name for the plant Sideritis scardica?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22274814" ], "ideal_answer": [ "Sideritis scardica is also known as ironwort or mountain tea." ], "exact_answer": [ "Mountain tea", "Ironwort" ], "type": "factoid", "id": "5c890e6d75a4a5d21900000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22274814", "endSection": "abstract" } ] }, { "body": "How are gas vesicle proteins used in imaging?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28880278", "http://www.ncbi.nlm.nih.gov/pubmed/28956265", "http://www.ncbi.nlm.nih.gov/pubmed/29483636", "http://www.ncbi.nlm.nih.gov/pubmed/27351374" ], "ideal_answer": [ "Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting.", "Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting", "Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents." ], "type": "summary", "id": "5ca9f5e4ecadf2e73f000052", "snippets": [ { "offsetInBeginSection": 217, "offsetInEndSection": 466, "text": "Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28956265", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 402, "text": "Here, we show that gas vesicles (GVs), a unique class of gas-filled protein nanostructures with differential magnetic susceptibility relative to water, can produce robust contrast in magnetic resonance imaging (MRI) at sub-nanomolar concentrations, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29483636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Gas vesicles (GVs) are a unique class of gas-filled protein nanostructures that are detectable at subnanomolar concentrations and whose physical properties allow them to serve as highly sensitive imaging agents for ultrasound and MRI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28880278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28880278", "endSection": "title" }, { "offsetInBeginSection": 774, "offsetInEndSection": 1040, "text": "Here, we demonstrate that genetic engineering of gas vesicles results in nanostructures with new mechanical, acoustic, surface, and functional properties to enable harmonic, multiplexed, and multimodal ultrasound imaging as well as cell-specific molecular targeting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27351374", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 502, "text": "Here, we show that gas vesicles (GVs), a unique class of gas-filled protein nanostructures with differential magnetic susceptibility relative to water, can produce robust contrast in magnetic resonance imaging (MRI) at sub-nanomolar concentrations, and that this contrast can be inactivated with ultrasound in situ to enable background-free imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29483636", "endSection": "abstract" } ] }, { "body": "From where is gamabufotalin (GBT) isolated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28631214", "http://www.ncbi.nlm.nih.gov/pubmed/25175164", "http://www.ncbi.nlm.nih.gov/pubmed/26894970", "http://www.ncbi.nlm.nih.gov/pubmed/30111043" ], "ideal_answer": [ "gamabufotalin (GBT) was isolated from toad venom." ], "exact_answer": [ "toad venom" ], "type": "factoid", "id": "5c9904eaecadf2e73f00002e", "snippets": [ { "offsetInBeginSection": 1219, "offsetInEndSection": 1610, "text": "RCFs of cinobufagin to gamabufotalin, bufotalin, bufalin and resibufogenin were determined as 1.05, 0.895, 1.09 and 0.913, respectively. The characteristic chromatogram and QAMS established in this study could effectively control the quality of toad venom and provide scientific evidence for the improvement of the quality standard of the toad venom to be described in Chinese Pharmacopoeia ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30111043", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 249, "text": "We identified three bufadienolides-the steroid-like compounds arenobufagin, gamabufotalin, and telocinobufagin-from the boreal toad,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28631214", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 235, "text": "In the current study, gamabufotalin (GBT) was isolated from toad venom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26894970", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Gamabufotalin, a bufadienolide compound from toad venom", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25175164", "endSection": "title" } ] }, { "body": "What are super-enhancers", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29754476" ], "ideal_answer": [ "Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators. Accumulating evidence points to the critical role that super-enhancers play in cell type-specific development and differentiation, as well as in the development of various diseases." ], "type": "summary", "id": "5c895e5ef9c2ba6b28000002", "snippets": [ { "offsetInBeginSection": 355, "offsetInEndSection": 719, "text": "Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators. Accumulating evidence points to the critical role that super-enhancers play in cell type-specific development and differentiation, as well as in the development of various diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29754476", "endSection": "abstract" } ] }, { "body": "Is Apelin usually decreased in diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19756893", "http://www.ncbi.nlm.nih.gov/pubmed/25914650", "http://www.ncbi.nlm.nih.gov/pubmed/29229313", "http://www.ncbi.nlm.nih.gov/pubmed/24721640" ], "ideal_answer": [ "Different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes." ], "exact_answer": "no", "type": "yesno", "id": "5caa0806ecadf2e73f000057", "snippets": [ { "offsetInBeginSection": 558, "offsetInEndSection": 816, "text": "Apelin has been shown to act on glucose and lipid metabolism but also to modulate insulin secretion. Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25914650", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 791, "text": "Upregulated expression of resistin, vaspin, apelin and TNF-\u03b1 plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29229313", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 816, "text": "Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25914650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19756893", "endSection": "title" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1593, "text": "In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg/dl, or OGTT-2h-PG 140-199mg/dl), the risk for developing diabetes was higher in those with higher plasma apelin concentration than in those with lower plasma apelin concentrations (10.6%/year vs. 5.1%/year, p<0.001).
CONCLUSIONS: Plasma apelin is a novel biomarker for predicting type 2 diabetes in men.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24721640", "endSection": "abstract" } ] }, { "body": "What is a mitosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30265292", "http://www.ncbi.nlm.nih.gov/pubmed/21984067", "http://www.ncbi.nlm.nih.gov/pubmed/20382757", "http://www.ncbi.nlm.nih.gov/pubmed/28372543" ], "ideal_answer": [ "Mitosomes are the simplest and the least well-studied type of anaerobic mitochondria. \tThe mitosomes have abandoned typical mitochondrial traits such as the mitochondrial genome and aerobic respiration and their single role known to date is the formation of iron-sulfur clusters" ], "exact_answer": [ "Simple and anaerobic mitochondria." ], "type": "factoid", "id": "5c9a6693ecadf2e73f000031", "snippets": [ { "offsetInBeginSection": 93, "offsetInEndSection": 179, "text": "Mitosomes are the simplest and the least well-studied type of anaerobic mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30265292", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 492, "text": "The mitosomes have abandoned typical mitochondrial traits such as the mitochondrial genome and aerobic respiration and their single role known to date is the formation of iron-sulfur clusters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28372543", "endSection": "abstract" }, { "offsetInBeginSection": 59, "offsetInEndSection": 138, "text": "a mitosome, a relict mitochondrion with a greatly reduced metabolic capability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21984067", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 421, "text": "he highly divergent mitochondrion-related organelle, the mitosome, in the anaerobic/microaerophilic protozoan parasite Entamoeba histolytica based on the potential mitochondrion-targeting signal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382757", "endSection": "abstract" } ] }, { "body": "What is the price of KYMRIAH treatment in 2019?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29764166" ], "ideal_answer": [ "Kymriah, produced by Novartis has a price tag of US$475,000." ], "exact_answer": [ "475,000 USD" ], "type": "factoid", "id": "5c897082d558e5f232000004", "snippets": [ { "offsetInBeginSection": 284, "offsetInEndSection": 646, "text": "At the time of the writing of this article, there are two CAR T cells available, Kymriah, produced by Novrtis with a price tag of US$475,000 and Yescarta produced by Gilead Pharmaceuticals with a price tag of US$373,000, neither price including the required hospital admission in order to administer the agent in addition to potential treatment of side effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29764166", "endSection": "abstract" } ] }, { "body": "Human dihydroorotate dehydrogenase is a drug target and is involved in what biosynthetic pathway", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26088338", "http://www.ncbi.nlm.nih.gov/pubmed/20334617", "http://www.ncbi.nlm.nih.gov/pubmed/17228860", "http://www.ncbi.nlm.nih.gov/pubmed/30145372", "http://www.ncbi.nlm.nih.gov/pubmed/1617622", "http://www.ncbi.nlm.nih.gov/pubmed/22542640", "http://www.ncbi.nlm.nih.gov/pubmed/18842591", "http://www.ncbi.nlm.nih.gov/pubmed/24900364", "http://www.ncbi.nlm.nih.gov/pubmed/30233375", "http://www.ncbi.nlm.nih.gov/pubmed/20702404", "http://www.ncbi.nlm.nih.gov/pubmed/1348618", "http://www.ncbi.nlm.nih.gov/pubmed/30200251", "http://www.ncbi.nlm.nih.gov/pubmed/16172019", "http://www.ncbi.nlm.nih.gov/pubmed/27481247", "http://www.ncbi.nlm.nih.gov/pubmed/18312275", "http://www.ncbi.nlm.nih.gov/pubmed/19351152", "http://www.ncbi.nlm.nih.gov/pubmed/27744189", "http://www.ncbi.nlm.nih.gov/pubmed/28666740", "http://www.ncbi.nlm.nih.gov/pubmed/25945707", "http://www.ncbi.nlm.nih.gov/pubmed/2386542", "http://www.ncbi.nlm.nih.gov/pubmed/22580100" ], "ideal_answer": [ "Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis", "The flavoenzyme dihydroorotate dehydrogenase (DHODH) catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which exerts vital functions in the cells, especially within DNA and RNA biosynthesis", "Dihydroorotate dehydrogenase (DHODH) catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which exerts vital functions in the cells, especially within DNA and RNA biosynthesis." ], "exact_answer": [ "pyrimidine biosynthesis" ], "type": "factoid", "id": "5cb0856decadf2e73f000058", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "The flavoenzyme dihydroorotate dehydrogenase (DHODH) catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which exerts vital functions in the cells, especially within DNA and RNA biosynthesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme of pyrimidine de novo biosynthesis pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481247", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 858, "text": "This review focuses on recent studies to exploit the fourth enzyme in the de novo pyrimidine biosynthetic pathway of P. falciparum, dihydroorotate dehydrogenase (PfDHODH), as a new target for drug discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The flavoenzyme dihydroorotate dehydrogenase catalyzes the stereoselective oxidation of (S)-dihydroorotate to orotate in the fourth of the six conserved enzymatic reactions involved in the de novo pyrimidine biosynthetic pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28666740", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 283, "text": "A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17228860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Dihydroorotate dehydrogenase (DHOD) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and is essential in Trypanosoma cruzi, the parasitic protist causing Chagas' disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16172019", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 304, "text": "Hence, we evaluated the essentiality of one enzyme in the pyrimidine biosynthetic pathway, dihydroorotate dehydrogenase (DHODH) from the eukaryotic parasite Trypanosoma brucei through gene knockdown studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18312275", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 327, "text": "Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19351152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900364", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 315, "text": "An important target for antimalarial chemotherapy is the enzyme dihydroorotate dehydrogenase from Plasmodium falciparum (PfDHODH), which is responsible for the conversion of dihydroorotate to orotate in the de novo pyrimidine biosynthetic pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27744189", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 453, "text": "Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and has been exploited as the target for therapy against proliferative and parasitic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22542640", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 339, "text": "Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The enzyme dihydroorotate dehydrogenase (DHODH) is a flavoenzyme that catalyses the oxidation of dihydroorotate to orotate in the de novo pyrimidine-biosynthesis pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25945707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Dihydroorotase and dihydroorotate dehydrogenase, two enzymes of the pyrimidine biosynthetic pathway, were purified from Plasmodium berghei to apparent homogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1348618", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 410, "text": "Dihydroorotate dehydrogenase (DHOD), a mitochondrially localized flavoenzyme, catalyzes the rate-limiting step of this pathway and is therefore an attractive antimalarial chemotherapeutic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18842591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme of pyrimidine de novo biosynthesis pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233375", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 462, "text": "Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19351152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Biochemical and molecular characterization of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase from Toxoplasma gondii.The pyrimidine biosynthesis pathway in the protozoan pathogen Toxoplasma gondii is essential for parasite growth during infection. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22580100", "endSection": "title" }, { "offsetInBeginSection": 748, "offsetInEndSection": 955, "text": "This review focuses on recent studies to exploit the fourth enzyme in the de novo pyrimidine biosynthetic pathway of P. falciparum, dihydroorotate dehydrogenase (PfDHODH), as a new target for drug discovery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "The novel anticancer drug candidate brequinar sodium (DuP 785, NSC 368390, 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinoline- carboxylic acid sodium salt) was shown previously to be an inhibitor of dihydroorotate dehydrogenase, the fourth enzyme of the de novo pyrimidine biosynthetic pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1617622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Dihydroorotate dehydrogenase (DHODH), in the de novo pyrimidine biosynthetic pathway, is the fourth enzyme of pyrimidine synthesis and is used to oxidize dihydroorotate and hence to orotat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30200251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "The novel anticancer drug candidate brequinar sodium [DuP 785, NSC 368390, 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinoline carboxylic acid sodium salt] inhibits dihydroorotate dehydrogenase, the fourth enzyme in the de novo pyrimidine biosynthetic pathway leading to the formation of UMP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2386542", "endSection": "abstract" } ] }, { "body": "List targets of classical analgesics.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19474215", "http://www.ncbi.nlm.nih.gov/pubmed/20942817" ], "ideal_answer": [ "Patient phenotypes in pharmacological pain treatment varies between individuals, which could be partly assigned to their genotypes regarding the targets of classical analgesics (OPRM1, PTGS2)" ], "exact_answer": [ [ "OPRM1" ], [ "PTGS2" ] ], "type": "list", "id": "5c9d18f1ecadf2e73f000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Patient phenotypes in pharmacological pain treatment varies between individuals, which could be partly assigned to their genotypes regarding the targets of classical analgesics (OPRM1, PTGS2) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20942817", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 339, "text": "Morphine is the current gold standard analgesic acting at MOP receptors but produces a range of variably troublesome side-effects, in particular tolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19474215", "endSection": "abstract" } ] }, { "body": "Is actin present in the nucleus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29568381", "http://www.ncbi.nlm.nih.gov/pubmed/30193156", "http://www.ncbi.nlm.nih.gov/pubmed/30019087", "http://www.ncbi.nlm.nih.gov/pubmed/29925947", "http://www.ncbi.nlm.nih.gov/pubmed/30312531" ], "ideal_answer": [ "Yes,\nThe revitalization of research into nuclear actin occurred after it was found that cellular stresses induce the nuclear localization and alter the structure of actin." ], "exact_answer": "yes", "type": "yesno", "id": "5ca0fdb0ecadf2e73f000049", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 812, "text": "Moreover, inhibition of ATM kinase or deficiency in nuclear actin polymerization causes carcinogenic RET/PTC chromosome rearrangements after DSBs induction in human cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568381", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1209, "text": " Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains that are essential for homology-directed repair in eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29925947", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 751, "text": "The discovery of nuclear actin opened new perspective on the field, suggesting that the nuclear activities of actin reflect the functions of primordial actin-like proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30019087", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 282, "text": " The revitalization of research into nuclear actin occurred after it was found that cellular stresses induce the nuclear localization and alter the structure of actin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "While it is long known that actin is part of the nuclear proteome, its properties and functions as regulated, functional and dynamically assembled actin filaments are only recently emerging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30193156", "endSection": "abstract" } ] }, { "body": "What is the indication for KYMRIAH?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29501911" ], "ideal_answer": [ "Kymriah\u2122 has been approved for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia." ], "exact_answer": [ "children and young adults with refractory or relapse B cell precursor acute lymphoblastic leukemia" ], "type": "factoid", "id": "5c896f60d558e5f232000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 357, "text": "Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah\u2122 and Yescarta\u2122) were recently approved by the FDA. Kymriah\u2122 is for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia and Yescarta\u2122 is for the treatment of adult patients with R/R large B cell lymphoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501911", "endSection": "abstract" } ] }, { "body": "What is the effect of NFIA on astrocyte differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30290178" ], "ideal_answer": [ "NFIA promotes astrocyte differentiation from neural precursor cells." ], "exact_answer": [ "Promotes", "Induces" ], "type": "factoid", "id": "5c8fe1f10101eac87000000a", "snippets": [ { "offsetInBeginSection": 647, "offsetInEndSection": 857, "text": "By searching for transcription factors that function at these elements, we identified NFIA and ATF3 as drivers of astrocyte differentiation from neural precursor cells while RUNX2 promotes astrocyte maturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30290178", "endSection": "abstract" } ] }, { "body": "What is the mode of action for Tocilizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27790001", "http://www.ncbi.nlm.nih.gov/pubmed/24729685", "http://www.ncbi.nlm.nih.gov/pubmed/22101760" ], "ideal_answer": [ "Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs" ], "type": "summary", "id": "5c960afaecadf2e73f00001e", "snippets": [ { "offsetInBeginSection": 498, "offsetInEndSection": 800, "text": "Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24729685", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 867, "text": "Several clinical studies have demonstrated that a humanized anti-IL-6 receptor antibody, tocilizumab, improves clinical symptoms in rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27790001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Tocilizumab is a recombinant humanized antihuman interleukin-6 receptor monoclonal antibody, which inhibits binding of IL-6 to its soluble (sIL-6R) and membrane-expressed (mIL-6R) receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22101760", "endSection": "abstract" } ] }, { "body": "Where is the protein protamine 2 expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28666211", "http://www.ncbi.nlm.nih.gov/pubmed/24869677", "http://www.ncbi.nlm.nih.gov/pubmed/28748416", "http://www.ncbi.nlm.nih.gov/pubmed/25516990", "http://www.ncbi.nlm.nih.gov/pubmed/26801756" ], "ideal_answer": [ "Human sperm express two types of protamine: protamine 1 (P1) and the family of protamine 2 (P2) proteins." ], "exact_answer": [ "sperm cells" ], "type": "factoid", "id": "5c9e6407ecadf2e73f000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "This work aimed at investigating the effect of resveratrol on (1) DNA integrity and (2) fertilizing capacity of sperm by quantifying the presence of key paternal transcripts considered as markers for male fertility (protamine 1 [PRM1] and protamine 2 [PRM2]) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28748416", "endSection": "abstract" }, { "offsetInBeginSection": 1186, "offsetInEndSection": 1323, "text": "biomarkers associated with spermatogenesis, including azoospermia-like (DAZL), phosphoglycerate kinase 2 (PGK2), and protamine 2 (PRM2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28666211", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 97, "text": " Protamines are sperm nuclear proteins with a crucial role in chromatin condensation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26801756", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 570, "text": "Expression of germ cell-specific proteins such as POU5F1, DAZL, TNP1, TNP2, PRM1 and PRM2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Human sperm express two types of protamine: protamine 1 (P1) and the family of protamine 2 (P2) proteins,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869677", "endSection": "abstract" } ] }, { "body": "Can miR-122 target RUNX2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30070328" ], "ideal_answer": [ "Yes, miR-122 directly targets RUNX2." ], "exact_answer": "yes", "type": "yesno", "id": "5c8fea130101eac87000000d", "snippets": [ { "offsetInBeginSection": 1373, "offsetInEndSection": 1511, "text": "MiR-122 functions as a tumor suppressor by inhibiting proliferation and inducing apoptosis, which is achieved by directly targeting RUNX2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30070328", "endSection": "abstract" } ] }, { "body": "Tocilizumab is an anti-TNF antibody, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22431927", "http://www.ncbi.nlm.nih.gov/pubmed/28401573", "http://www.ncbi.nlm.nih.gov/pubmed/19882783", "http://www.ncbi.nlm.nih.gov/pubmed/21949922", "http://www.ncbi.nlm.nih.gov/pubmed/24286116", "http://www.ncbi.nlm.nih.gov/pubmed/20979549", "http://www.ncbi.nlm.nih.gov/pubmed/26751942", "http://www.ncbi.nlm.nih.gov/pubmed/19368420", "http://www.ncbi.nlm.nih.gov/pubmed/24741293", "http://www.ncbi.nlm.nih.gov/pubmed/29495891", "http://www.ncbi.nlm.nih.gov/pubmed/21234291" ], "ideal_answer": [ "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor licensed in 2009", "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations.", "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor", "was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody", "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6 receptor licensed in 2009 and recommendations consider TCZ as one of the treatements indicated after methotrexate and/or TNF inhibitors failure in adult RA." ], "exact_answer": "no", "type": "yesno", "id": "5c960d88ecadf2e73f00001f", "snippets": [ { "offsetInBeginSection": 595, "offsetInEndSection": 676, "text": "was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28401573", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 658, "text": "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations. RA management guidelines and recommendations consider TCZ as one of the bDMARDS indicated after methotrexate or other conventional synthetic DMARDs and/or TNF inhibitors failure in adult RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29495891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19368420", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 547, "text": "METHODS\nPatients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-\u03b1 inhibitors for 16 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24286116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "The recent development of biological agents, namely, anti-tumour necrosis factor alpha (TNF-\u03b1) agents (infliximab, adalimumab and etanercept), anti- CD20 monoclonal antibody (rituximab) and anti-interleukin 6 receptor (IL-6R) monoclonal antibody (tocilizumab), represents a major breakthrough for the treatment of immune-mediated disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26751942", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 736, "text": "Recently, an anti-IL-6 receptor monoclonal antibody, tocilizumab, has been licensed for the treatment as monotherapy or in combination with methotrexate of moderate to severe RA, when disease modifying anti-rheumatic drugs or anti-tumour necrosis factors (TNF) have failed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21949922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Tocilizumab is a monoclonal humanized anti-IL-6-receptor antibody used for the treatment of rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431927", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 913, "text": "Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24741293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody, which binds to circulating soluble IL-6 receptor and membrane-expressed IL-6 receptor, inhibiting IL-6 binding to both forms of IL-6 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20979549", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 309, "text": "Subsequent options include a TNF-alpha antagonist, followed by rituximab or possibly abatacept; (2) Tocilizumab, a monoclonal antibody, inhibits interleukin-6 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19882783", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 177, "text": "Tocilizumab (TCZ) is a monoclonal antibody which inhibits the interleukin-6 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21234291", "endSection": "abstract" } ] }, { "body": "Is it possible to analyze exosomes with FACS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29783743", "http://www.ncbi.nlm.nih.gov/pubmed/26154623", "http://www.ncbi.nlm.nih.gov/pubmed/30290833", "http://www.ncbi.nlm.nih.gov/pubmed/26598503" ], "ideal_answer": [ "Yes,\na novel strategy for generating metabolically-labeled fluorescent exosomes that can be counted by flow cytometry assay (FACS) and characterized." ], "exact_answer": "yes", "type": "yesno", "id": "5c9e6ab9ecadf2e73f000035", "snippets": [ { "offsetInBeginSection": 1458, "offsetInEndSection": 1516, "text": "whose presence was validated by a bead-exosome FACS assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26154623", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 467, "text": "We analyzed exosomes from mouse (C57Bl/6) and breast, lung, and ovarian cancer patient samples and cultured cancer cells with different approaches, including nanoparticle tracking analysis, biolayer interferometry, FACS, and electron microscopy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598503", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 924, "text": "we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30290833", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 594, "text": "we used a novel strategy for generating metabolically-labeled fluorescent exosomes that can be counted by flow cytometry assay (FACS) and characterized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29783743", "endSection": "abstract" } ] }, { "body": "Which company developed opdivo?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30293207" ], "ideal_answer": [ "Opdivo or nivolumab was developed by Bristol-Myers Squibb." ], "exact_answer": [ "Bristol-Myers Squibb" ], "type": "factoid", "id": "5c910ae0ecadf2e73f000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Bristol-Myers Squibb) of nivolumab (Opdivo\u00ae) to submit evidence of its clinical and cost effectiveness for metastatic or unresectable urothelial cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30293207", "endSection": "abstract" } ] }, { "body": "What are DMARDs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22420649", "http://www.ncbi.nlm.nih.gov/pubmed/20681888", "http://www.ncbi.nlm.nih.gov/pubmed/27604908", "http://www.ncbi.nlm.nih.gov/pubmed/28324149", "http://www.ncbi.nlm.nih.gov/pubmed/7732491", "http://www.ncbi.nlm.nih.gov/pubmed/25603037", "http://www.ncbi.nlm.nih.gov/pubmed/25630309", "http://www.ncbi.nlm.nih.gov/pubmed/27538766", "http://www.ncbi.nlm.nih.gov/pubmed/25244345", "http://www.ncbi.nlm.nih.gov/pubmed/25943001", "http://www.ncbi.nlm.nih.gov/pubmed/25943002", "http://www.ncbi.nlm.nih.gov/pubmed/22298075", "http://www.ncbi.nlm.nih.gov/pubmed/24129128", "http://www.ncbi.nlm.nih.gov/pubmed/23961667", "http://www.ncbi.nlm.nih.gov/pubmed/18824833", "http://www.ncbi.nlm.nih.gov/pubmed/30448932", "http://www.ncbi.nlm.nih.gov/pubmed/25504789", "http://www.ncbi.nlm.nih.gov/pubmed/24470443", "http://www.ncbi.nlm.nih.gov/pubmed/23959574", "http://www.ncbi.nlm.nih.gov/pubmed/9608316", "http://www.ncbi.nlm.nih.gov/pubmed/28679392", "http://www.ncbi.nlm.nih.gov/pubmed/12468815", "http://www.ncbi.nlm.nih.gov/pubmed/23716132" ], "ideal_answer": [ "To determine the utility of ultrasonography in guiding modification of disease-modifying anti-rheumatic drug (DMARD) and steroid therapy for inflammatory arthritis (IA)", "DMARDs are Disease Modifying anti-rheumatic drugs (DMARD).", "Treatment with disease-modifying antirheumatic drugs (DMARDs) was 61% (claims data)", "Treatment with disease-modifying antirheumatic drugs (DMARDs)", "Treatment with disease-modifying antirheumatic drugs (DMARDs) was 61% (claims data) and" ], "exact_answer": [ "Disease Modifying anti-rheumatic drugs" ], "type": "factoid", "id": "5c960f21ecadf2e73f000020", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 179, "text": "To determine the utility of ultrasonography in guiding modification of disease-modifying anti-rheumatic drug (DMARD) and steroid therapy for inflammatory arthritis (IA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27538766", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 262, "text": "disease-modifying antirheumatic drugs (DMARDs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27604908", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1352, "text": "Treatment with disease-modifying antirheumatic drugs (DMARDs) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28324149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "[DMARDs (disease-modifying antirheumatic drugs)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23961667", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Disease-modifying antirheumatic drugs (DMARDs) have largely contributed to recent paradigm shift of rheumatoid arthritis (RA) treatment strategy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23961667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND\nBiologic disease-modifying antirheumatic drugs (DMARDs) are increasingly used for rheumatoid arthritis (RA) treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28679392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Tocilizumab (TCZ) and tumour necrosis factor inhibitors (TNFi) are recommended for the treatment of rheumatoid arthritis (RA) in patients with inadequate response (IR) to prior disease-modifying antirheumatic drugs (DMARDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25630309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "BACKGROUND\nRheumatoid arthritis (RA) is a progressive autoimmune disorder of joints that is associated with high health care costs, yet guidance is lacking on how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs), a class of medications that is the major cost driver in RA management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25943001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND\nTherapy of rheumatoid arthritis (RA) is typically characterized by the sequential use of disease-modifying anti-rheumatic drugs (DMARDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12468815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "There are only six DMARDs (disease modifying anti-rheumatic drugs) available in the clinical practice, such as gold sodium thiomalate, D-penicillamine, bucillamine, auranofin, salazosulphapyridine, and lobenzarit disodium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7732491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Tofacitinib (Xeljanz(\u00ae)) is the first approved drug in a new class of disease modifying antirheumatic drugs (DMARDs), the Janus kinase (JAK) inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23716132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "OBJECTIVE\nDisease-modifying antirheumatic drugs (DMARDs) are the standard of care for rheumatoid arthritis (RA); however, studies have found that many patients do not receive them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24470443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) pharmacotherapy and should be initiated promptly after RA diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23959574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "OBJECTIVES\nWhen rheumatoid arthritis (RA) patients have achieved sustained good clinical responses can their disease-modifying anti-rheumatic drugs (DMARDs) be reduced or discontinued?", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129128", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "BACKGROUND\nGiven the availability of a number of alternative biologic treatment options and other novel disease-modifying antirheumatic drugs (DMARDs) for the treatment of patients with rheumatoid arthritis (RA), clinicians are faced with an increasingly challenging choice regarding optimal treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25943002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "BACKGROUND\nTreatment of juvenile idiopathic arthritis (JIA) with disease-modifying antirheumatic drugs (DMARDs) may improve outcomes compared to conventional therapy (e.g., non-steroidal anti-inflammatory drugs, intra-articular corticosteroids).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22420649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Disease modifying antirheumatic drugs (DMARDs) is a category of drugs which is used as medication in various arthritic conditions to arrest the progression of disease along with relief from pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25244345", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 330, "text": "For this purpose, all patients with the diagnosis of RA should be treated by disease-modifying antirheumatic drugs (DMARDs) including biologic DMARDs and non-biologic DMARDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22298075", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 408, "text": "(2) What is the search volume for disease-modifying antirheumatic drugs (DMARDs)?", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30448932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "OBJECTIVES: Patients and rheumatologists have a number of options to consider for the treatment of rheumatoid arthritis (RA), including biologic response modifier (BRM) therapy and diseasemodifying antirheumatic drugs (DMARDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "To explore what considerations patients have when deciding about disease-modifying antirheumatic drugs (DMARDs) and what information patients need to participate in the decision-making process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25504789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Disease-modifying antirheumatic drug (DMARD) therapy is now clearly accepted as the primary treatment for rheumatoid arthritis, with an increasing emphasis on use of combination therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9608316", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 385, "text": "(2) What is the search volume for disease-modifying antirheumatic drugs (DMARDs)?", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30448932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The efficacy of the biologic disease-modifying antirheumatic drugs (DMARDs) shown in clinical trials may be jeopardized due to prevalent poor patient adherence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20681888", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 496, "text": "Although methotrexate has retained its place as the first-line agent, there has been great interest in comparing biologicals to conventional Disease Modifying Anti Rheumatic Drugs (DMARDs) over the past few years with the updated guidelines from both the American College of Rheumatology and European League Against Rheumatism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25603037", "endSection": "abstract" } ] }, { "body": "What is the aim of the MitoCeption protocol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28287607", "http://www.ncbi.nlm.nih.gov/pubmed/25766410" ], "ideal_answer": [ "The MitoCeption protocol directly and quantitatively transfer mitochondria, isolated from cell type A, to recipient cell type B." ], "exact_answer": [ "Mitochondrial transfer" ], "type": "factoid", "id": "5c9e6e99ecadf2e73f000036", "snippets": [ { "offsetInBeginSection": 782, "offsetInEndSection": 1000, "text": " The MitoCeption protocol described here allows the transfer of the mitochondria isolated beforehand from the donor cells to the target cells, using MSC mitochondria and glioblastoma stem cells (GSC) as a model system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287607", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 618, "text": "We designed a protocol (MitoCeption) to directly and quantitatively transfer mitochondria, isolated from cell type A, to recipient cell type B. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25766410", "endSection": "abstract" } ] }, { "body": "Can prevnar 13 be used in children?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22045904" ], "ideal_answer": [ "Yes, PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2, 4, 6, and 12-15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications." ], "exact_answer": "yes", "type": "yesno", "id": "5c915e51ecadf2e73f00000c", "snippets": [ { "offsetInBeginSection": 721, "offsetInEndSection": 1062, "text": "PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2, 4, 6, and 12-15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22045904", "endSection": "abstract" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1580, "text": "Based on published immunogenicity and safety data, as well as the recent recommendations by the ACIP for routine use in infants and indications for high-risk pediatric patients, PCV13 is a revised formulation of pneumococcal vaccine that should be included on pharmacy formularies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22045904", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 148, "text": "To review the immunogenicity, efficacy, and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in pediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22045904", "endSection": "abstract" } ] }, { "body": "Was stelara developed by Amgen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28976302" ], "ideal_answer": [ "Stelara was developed by Janssen Pharmaceuticals, Inc., Horsham, PA, USA." ], "exact_answer": "no", "type": "yesno", "id": "5c9160bcecadf2e73f00000d", "snippets": [ { "offsetInBeginSection": 264, "offsetInEndSection": 484, "text": "NICE does not specifically recommend switching from one biologic to another, and only ustekinumab (UST; STELARA\u00ae, Janssen Pharmaceuticals, Inc., Horsham, PA, USA) is recommended after anti-tumour necrosis factor failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28976302", "endSection": "abstract" } ] }, { "body": "List off label uses for Rituximab.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29797711", "http://www.ncbi.nlm.nih.gov/pubmed/28742259", "http://www.ncbi.nlm.nih.gov/pubmed/29574922", "http://www.ncbi.nlm.nih.gov/pubmed/30185361", "http://www.ncbi.nlm.nih.gov/pubmed/18270863", "http://www.ncbi.nlm.nih.gov/pubmed/28536935" ], "ideal_answer": [ "Off label uses for rituximab are for poly- and dermatomyositis, multiple sclerosis, immune thrombocytopenia, systemic lupus erythematosus (SLE), lupus nephritis (LN), and other immune diseases." ], "exact_answer": [ [ "poly- and dermatomyositis" ], [ "multiple sclerosis" ], [ "auto immune disease" ], [ "immune thrombocytopenia" ], [ "systemic lupus erythematosus (SLE)" ], [ "lupus nephritis (LN)" ] ], "type": "list", "id": "5c961603ecadf2e73f000022", "snippets": [ { "offsetInBeginSection": 265, "offsetInEndSection": 491, "text": "Analysis of the data of the GRAID-2 registry for poly- and dermatomyositis.RESULTS: In 22\u00a0of the 23\u00a0patients in the GRAID-2 registry, rituximab (RIX) was administered, while 1\u00a0patient was given tocilizumab as off-label therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28536935", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 77, "text": "Off-label use of rituximab to treat MS patients in Sweden is high", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29797711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Off-label use of rituximab in autoimmune disease in the Top End of the Northern Territory, 2008-2016.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28742259", "endSection": "title" }, { "offsetInBeginSection": 17, "offsetInEndSection": 376, "text": "immune thrombocytopenia who do not adequately respond to first-line therapy, there is no clear consensus on which second-line therapy to initiate and when. This situation leads to suboptimal approaches, including prolonged exposure to treatments that are not intended for long-term use (eg, corticosteroids) and overuse of off-label therapies (eg, rituximab) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29574922", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 288, "text": "Conventional treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN) is associated with damage accrual, hence increased morbidity rate. Off-label use of rituximab (RTX) has shown significant promise in this patient group; however, data are still controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30185361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Outcomes of rituximab therapy in refractory lupus: A meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30185361", "endSection": "title" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1077, "text": "Rituximab seems to have an interesting benefit-to-risk ratio in Wegener granulomatosis (excepted in granulomatous lesions), HCV-associated symptomatic cryoglobulinemia in patients unresponsive to anti-viral therapy, pemphigus and thrombotic thrombocytopenic purpura.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18270863", "endSection": "abstract" } ] }, { "body": "Can mitochondria pass through membrane nanotubes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29362447", "http://www.ncbi.nlm.nih.gov/pubmed/29335691" ], "ideal_answer": [ "Yes,\nMembrane nanotubes (MNTs) act as \"highways\" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs)." ], "exact_answer": "yes", "type": "yesno", "id": "5c9e766becadf2e73f000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Membrane nanotubes (MNTs) act as \"highways\" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29362447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Membrane nanotubes play important functional roles in numerous cell activities such as cellular transport and communication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335691", "endSection": "abstract" } ] }, { "body": "What is Quorum Sensing in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22825856", "http://www.ncbi.nlm.nih.gov/pubmed/29130162", "http://www.ncbi.nlm.nih.gov/pubmed/29095463", "http://www.ncbi.nlm.nih.gov/pubmed/29130160", "http://www.ncbi.nlm.nih.gov/pubmed/22269240", "http://www.ncbi.nlm.nih.gov/pubmed/15151251", "http://www.ncbi.nlm.nih.gov/pubmed/27634359", "http://www.ncbi.nlm.nih.gov/pubmed/23125205", "http://www.ncbi.nlm.nih.gov/pubmed/27688408", "http://www.ncbi.nlm.nih.gov/pubmed/20819164" ], "ideal_answer": [ "In many pathogenic microorganisms, communication systems, collectively termed quorum sensing (QS),", "In many pathogenic microorganisms, communication systems, collectively termed quorum sensing (QS), have been observed", "In most bacteria, a global level of regulation, termed quorum sensing (QS), exists involving intercellular communication via the production and response to cell density-dependent signal molecules." ], "type": "summary", "id": "5c978924ecadf2e73f000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Many Proteobacteria synthesize acyl-homoserine lactone (AHL) molecules for use as signals in cell density-dependent gene regulation known as quorum sensing (QS) and response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29130162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "In most bacteria, a global level of regulation, termed quorum sensing (QS), exists involving intercellular communication via the production and response to cell density-dependent signal molecules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29130160", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 596, "text": " In many pathogenic microorganisms, communication systems, collectively termed quorum sensing (QS), have been observed to control a number of bacterial behaviours including expression of virulence factors and the development of biofilms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29095463", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1049, "text": "Bacteria can communicate within their own species (intra-species) but also between species (inter-species), for which they employ an autoinducer-2 quorum sensing system which is called the universal language of the bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27688408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Quorum sensing is a signaling mechanism through which bacteria modulate a number of cellular functions (genes), including sporulation, biofilm formation, bacteriocin production, virulence responses, as well as others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15151251", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 395, "text": "Quorum sensing is a mechanism of cell-to-cell communication and is mediated by extracellular chemical signals generated by the bacteria when specific cell densities are reached.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15151251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Quorum sensing is used by a large variety of bacteria to regulate gene expression in a cell-density-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22825856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "BACKGROUND\nQuorum sensing or the bacterial information flow in an orchestrated manner is an essential feature of many pathogenic bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634359", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1056, "text": "Quorum sensing is the means of communication between these bacteria to regulate a wide range of behavior patterns among them.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23125205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Quorum sensing is the phenomenon, whereby bacteria use signal molecules to communicate with each other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20819164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The term 'quorum sensing' describes intercellular bacterial communication which regulates bacterial gene expression according to population cell density.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27688408", "endSection": "abstract" } ] }, { "body": "What is the cause of Krabbe disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29316812", "http://www.ncbi.nlm.nih.gov/pubmed/28598007", "http://www.ncbi.nlm.nih.gov/pubmed/29391017" ], "ideal_answer": [ "Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase." ], "exact_answer": [ "deficiency of \u03b2-galactocerebrosidase" ], "type": "factoid", "id": "5c9efde8ecadf2e73f000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Krabbe disease (KD) is a rare disease caused by the deficiency of \u03b2-galactocerebrosidase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28598007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29316812", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 118, "text": "Krabbe disease is a rare neurodegenerative genetic disorder caused by deficiency of galactocerebrosidase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29391017", "endSection": "abstract" } ] }, { "body": "Name a CFL2 mutation which is associated with nemaline myopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22560515" ], "ideal_answer": [ "A mutation in CFL2 was identified in a family with nemaline myopathy, namely a homozygous missense mutation in exon 2 (c.19G>A, p.Val7Met)." ], "exact_answer": [ "c.19G>A", "p.Val7Met" ], "type": "factoid", "id": "5c89623bf9c2ba6b28000004", "snippets": [ { "offsetInBeginSection": 469, "offsetInEndSection": 703, "text": "Because a mutation in CFL2 was identified in a family with nemaline myopathy, we performed sequence analysis of the gene and a novel homozygous missense mutation in exon 2 (c.19G>A, p.Val7Met) of CFL2 was identified in both siblings. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22560515", "endSection": "abstract" } ] }, { "body": "What cellular process is the gene product of NANOG involved in?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26339994", "http://www.ncbi.nlm.nih.gov/pubmed/29177763", "http://www.ncbi.nlm.nih.gov/pubmed/29414604", "http://www.ncbi.nlm.nih.gov/pubmed/29243835", "http://www.ncbi.nlm.nih.gov/pubmed/29486740", "http://www.ncbi.nlm.nih.gov/pubmed/29204746", "http://www.ncbi.nlm.nih.gov/pubmed/28866747" ], "ideal_answer": [ "NANOG is a transcription factor and a biomarker of cancer and pluripotent stem cells." ], "exact_answer": [ "regulation of transcription" ], "type": "factoid", "id": "5c9789a9ecadf2e73f000024", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 187, "text": "The objective of this study was to explore the prognostic value of cancer stem cell markers, namely CD133, NANOG, and NOTCH1, in early stage oral squamous cell carcinoma (OSCC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28866747", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 378, "text": " transcription factors (TFs) such as Oct4, Sox2, and Nanog", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177763", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 636, "text": "expression of breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29243835", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1310, "text": "pluripotency markers OCT-4, SOX-2 and NANOG ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29204746", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 377, "text": "The obtained induced pluripotent stem cell (iPSC) line showed pluripotency verified by the expression of pluripotency markers, NANOG, SOX2, OCT4,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29414604", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 226, "text": "Nanog is one of the transcription factors that are essential for stem cellular physiology process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26339994", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1069, "text": "CONCLUSIONS\nNanog has been recognized as a critical pluripotency gene in stem cell regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29486740", "endSection": "abstract" } ] }, { "body": "Name the uses of Sideritis scardica in traditional medicine.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24487281" ], "ideal_answer": [ "Sideritis scardica is used in traditional medicine as a loosening agent in bronchitis and bronchial asthma; against the common cold and lung emphysema; in the treatment of inflammation, gastrointestinal disorders and coughs; and as an active constituent of dietary supplements for the prevention of anemia. Sideritis scardica has been attributed a broad range of properties such as antimicrobial, anti-inflammatory, cytotoxic, antioxidant, gastroprotective, antiglioma, and triple monoamine reuptake inhibition." ], "exact_answer": [ [ "against inflammation" ], [ "against gastrointestinal disorders" ], [ "against anemia" ], [ "against bronchitis" ] ], "type": "list", "id": "5c890ff475a4a5d219000010", "snippets": [ { "offsetInBeginSection": 106, "offsetInEndSection": 396, "text": "It is used in traditional medicine as a loosening agent in bronchitis and bronchial asthma; against the common cold and lung emphysema; in the treatment of inflammation, gastrointestinal disorders and coughs; and as an active constituent of dietary supplements for the prevention of anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24487281", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1777, "text": "A broad range of activities of plant extracts and fractions as antimicrobial, anti-inflammatory, cytotoxic, antioxidant, gastroprotective, antiglioma, and triple monoamine reuptake inhibition as well as cultivation of the species as an approach for conservation of the natural habitats and provision of herb with high and permanent quality has also been presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24487281", "endSection": "abstract" } ] }, { "body": "What are the phenotypic features of the autosomal dominant, development disease, Noonans syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20882035", "http://www.ncbi.nlm.nih.gov/pubmed/24447602", "http://www.ncbi.nlm.nih.gov/pubmed/12439898", "http://www.ncbi.nlm.nih.gov/pubmed/28144274", "http://www.ncbi.nlm.nih.gov/pubmed/29084544" ], "ideal_answer": [ "Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate", "Noonan syndrome is an autosomal dominant disease and is characterized by developmental problems. Symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate" ], "type": "summary", "id": "5c978a2aecadf2e73f000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28144274", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 605, "text": "Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES).METHODS: TS/WES was performed to identify mutations in ten Chinese patients who exhibited the following manifestations: potential facial dysmorphisms, short stature, congenital heart defects, and developmental delay. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29084544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Noonan's syndrome is an autosomal dominant genetic disorder with high phenotypic variability, characterized mainly by facial dysmorphism, congenital heart disease and short stature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24447602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Noonan syndrome is an autosomal dominant disease characterized by dysmorphic features, webbed neck, cardiac anomalies, short stature and cryptorchidism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20882035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Noonan syndrome or new autosomal dominant condition with coarctation of the aorta, hypertrophic cardiomyopathy, and minor anomalies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12439898", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "This is a report on a father and his two children with an apparent autosomal dominant condition characterized by craniofacial anomalies, coarctation of the aorta, hypertrophic cardiomyopathy, and other structural heart abnormalities with normal psychomotor development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12439898", "endSection": "abstract" } ] }, { "body": "Are protamines ubiquitously expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29797354" ], "ideal_answer": [ "No,\nProtamines are nuclear proteins which are specifically expressed in haploid male germ cells." ], "exact_answer": "no", "type": "yesno", "id": "5c9f1b0cecadf2e73f00003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Protamines are nuclear proteins which are specifically expressed in haploid male germ cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29797354", "endSection": "abstract" } ] }, { "body": "Are Crocus sativus compounds being considered against Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28471166" ], "ideal_answer": [ "Yes, it has been observed that Crocus sativus extracts and compounds have a positive effect against Alzheimer's disease." ], "exact_answer": "yes", "type": "yesno", "id": "5c891d5075a4a5d219000011", "snippets": [ { "offsetInBeginSection": 169, "offsetInEndSection": 439, "text": "Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471166", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1690, "text": "Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing A\u03b2 pathological manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471166", "endSection": "abstract" } ] }, { "body": "Rickettsia felis was described as a human pathogen almost two decades ago, what is it's main arthropod vector?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19645274", "http://www.ncbi.nlm.nih.gov/pubmed/26824189", "http://www.ncbi.nlm.nih.gov/pubmed/21722253", "http://www.ncbi.nlm.nih.gov/pubmed/24149035", "http://www.ncbi.nlm.nih.gov/pubmed/29217417", "http://www.ncbi.nlm.nih.gov/pubmed/29079185" ], "ideal_answer": [ "Cat fleas (Ctenocephalides felis) carry Rickettsia felis", "Cat fleas (Ctenocephalides felis) carrying Rickettsia felis and Bartonella species in Hong Kong.", "Cat fleas (Ctenocephalides felis) carrying Rickettsia felis and Bartonella species in Hong Kong" ], "exact_answer": [ "Cat fleas (Ctenocephalides felis)" ], "type": "factoid", "id": "5c9791d2ecadf2e73f000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Cat fleas (Ctenocephalides felis) carrying Rickettsia felis and Bartonella species in Hong Kong.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217417", "endSection": "title" }, { "offsetInBeginSection": 231, "offsetInEndSection": 358, "text": " Morphological examination of 174 fleas from dogs and cats living in Hong Kong revealed only cat fleas (Ctenocephalides felis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217417", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 560, "text": "The main arthropod reservoir and vector is the cat flea, Ctenocephalides felis, yet more than 20 other species of fleas, ticks, and mites species have been reported to harbour R. felis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24149035", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 437, "text": "The cat flea, Ctenocephalides felis, is currently the only known biological vector of R. felis; however, molecular evidence of R. felis in other species of fleas as well as in ticks and mites suggests a variety of arthropod hosts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19645274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 451, "text": "Rickettsia felis: from a rare disease in the USA to a common cause of fever in sub-Saharan Africa.Rickettsia felis is a spotted fever group rickettsia that has been definitely described in 2002. Within the last 20 years, there have been a growing number of reports implicating R. felis as a human pathogen, parallel to the fast-growing reports of the worldwide detection of R. felis in arthropod hosts, mainly the cat flea Ctenocephalides felis felis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21722253", "endSection": "title" }, { "offsetInBeginSection": 437, "offsetInEndSection": 622, "text": "The main arthropod reservoir and vector is the cat flea, Ctenocephalides felis, yet more than 20 other species of fleas, ticks, and mites species have been reported to harbour R. felis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24149035", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 234, "text": "Another rickettsia, Rickettsia felis, found in cat fleas, Ctenocephalides felis, has also been implicated as a potential human pathogen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26824189", "endSection": "abstract" } ] }, { "body": "Are there any anti-amyloid antibody approved as drug for Alzheimer's disease treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29607687", "http://www.ncbi.nlm.nih.gov/pubmed/26697860" ], "ideal_answer": [ "No new drugs have been approved during the past 15 years; and the available medications are not cost-effective." ], "exact_answer": "no", "type": "yesno", "id": "5ca0848aecadf2e73f000044", "snippets": [ { "offsetInBeginSection": 873, "offsetInEndSection": 1222, "text": "Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26697860", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 626, "text": "anti-Amyloid agents (13.30%)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29607687", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 314, "text": "no new drugs have been approved during the past 15\u00a0years; and the available medications are not cost-effective. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29607687", "endSection": "abstract" } ] }, { "body": "Do Crocus sativus extracts loosen the blood-brain barrier?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28471166" ], "ideal_answer": [ "No, in vitro and in vivo experiments show that the Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB)." ], "exact_answer": "no", "type": "yesno", "id": "5c891e5575a4a5d219000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid \u03b2 Load and Related Toxicity in 5XFAD Mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471166", "endSection": "title" }, { "offsetInBeginSection": 523, "offsetInEndSection": 1120, "text": "In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of A\u03b2. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to mice diet) on the BBB tightness and function that was associated with reduced A\u03b2 load and related pathological changes in 5XFAD mice used as an AD model. Reduced A\u03b2 load could be explained, at least in part, by Crocus sativus extract effect to enhance A\u03b2 clearance pathways including BBB clearance, enzymatic degradation and ApoE clearance pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28471166", "endSection": "abstract" } ] }, { "body": "Are artificial blood cells available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20234994", "http://www.ncbi.nlm.nih.gov/pubmed/28406466" ], "ideal_answer": [ "No,\nThe critical point for the break through for artificial blood products did not come yet but could be ahead-" ], "exact_answer": "no", "type": "yesno", "id": "5ca0fa96ecadf2e73f000048", "snippets": [ { "offsetInBeginSection": 1638, "offsetInEndSection": 1745, "text": "The critical point for the break through for artificial blood products did not come yet but could be ahead-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20234994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28406466", "endSection": "abstract" } ] }, { "body": "Have apolipoprotein mimetics been used in clinical trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25157031" ], "ideal_answer": [ "Yes, apolipoprotein mimetics have entered clinical trials." ], "exact_answer": "yes", "type": "yesno", "id": "5c895cf0f9c2ba6b28000001", "snippets": [ { "offsetInBeginSection": 1230, "offsetInEndSection": 1329, "text": "One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25157031", "endSection": "abstract" } ] }, { "body": "What are 2 organisms that can cause Human toxocariasis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24808249", "http://www.ncbi.nlm.nih.gov/pubmed/29733009", "http://www.ncbi.nlm.nih.gov/pubmed/30050644", "http://www.ncbi.nlm.nih.gov/pubmed/18179629", "http://www.ncbi.nlm.nih.gov/pubmed/28761463", "http://www.ncbi.nlm.nih.gov/pubmed/25910623" ], "ideal_answer": [ "Human toxocariasis , a worldwide parasitic disease , is caused by the larval stage of intestinal nematodes of dogs and cats , namely Toxocara canis and Toxocara cati", "Human toxocariasis, a worldwide parasitic disease, is caused by the larval stage of intestinal nematodes of dogs and cats, namely Toxocara canis and Toxocara cati", "human toxocariasis, a worldwide parasitic disease, is caused by the larval stage of intestinal nematodes of dogs and cats, namely toxocara canis and toxocara cati" ], "exact_answer": [ [ "Toxocara cati" ], [ "Toxocara canis" ] ], "type": "list", "id": "5c979ffcecadf2e73f000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Human toxocariasis, a worldwide parasitic disease, is caused by the larval stage of intestinal nematodes of dogs and cats, namely Toxocara canis and Toxocara cati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29733009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Human toxocariasis which is caused mainly by the larvae of Toxocara canis and Toxocara cati, is a worldwide zoonotic disease that can be a potentially serious human infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25910623", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "BACKGROUND\nToxocariasis is a prevalent zoonosis disease caused by the closely related nematode species Toxocara canis and Toxocara cati which parasitise Canidae and Felidae respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28761463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Human toxocariasis is a zoonosis caused by infection with larvae of the ascarid nematode Toxocara canis and, less frequently, T. cati.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18179629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Toxocariasis is a preventable parasitic disease that is caused by the dog and cat roundworms Toxocara cani and T. cati, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24808249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Human toxocariasis is a cosmopolitan parasitic zoonosis caused by Toxocara canis and Toxocara cati which are roundworms of dogs and cats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30050644", "endSection": "abstract" } ] }, { "body": "What is the dbSUPER database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26438538" ], "ideal_answer": [ "dbSUPER is the first integrated and interactive database of super-enhancers, with the primary goal of providing a resource for assistance in further studies related to transcriptional control of cell identity and disease. dbSUPER provides a responsive and user-friendly web interface to facilitate efficient and comprehensive search and browsing. The data can be easily sent to Galaxy instances, GREAT and Cistrome web-servers for downstream analysis, and can also be visualized in the UCSC genome browser where custom tracks can be added automatically. The data can be downloaded and exported in variety of formats. Furthermore, dbSUPER lists genes associated with super-enhancers and also links to external databases such as GeneCards, UniProt and Entrez. dbSUPER also provides an overlap analysis tool to annotate user-defined regions." ], "type": "summary", "id": "5c8960a6f9c2ba6b28000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "dbSUPER: a database of super-enhancers in mouse and human genome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26438538", "endSection": "title" }, { "offsetInBeginSection": 565, "offsetInEndSection": 1460, "text": "We developed dbSUPER (http://bioinfo.au.tsinghua.edu.cn/dbsuper/), the first integrated and interactive database of super-enhancers, with the primary goal of providing a resource for assistance in further studies related to transcriptional control of cell identity and disease. dbSUPER provides a responsive and user-friendly web interface to facilitate efficient and comprehensive search and browsing. The data can be easily sent to Galaxy instances, GREAT and Cistrome web-servers for downstream analysis, and can also be visualized in the UCSC genome browser where custom tracks can be added automatically. The data can be downloaded and exported in variety of formats. Furthermore, dbSUPER lists genes associated with super-enhancers and also links to external databases such as GeneCards, UniProt and Entrez. dbSUPER also provides an overlap analysis tool to annotate user-defined regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26438538", "endSection": "abstract" } ] }, { "body": "List places in the body where somatostatin is produced.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25777539", "http://www.ncbi.nlm.nih.gov/pubmed/23370538", "http://www.ncbi.nlm.nih.gov/pubmed/24627166", "http://www.ncbi.nlm.nih.gov/pubmed/19819962", "http://www.ncbi.nlm.nih.gov/pubmed/23894587" ], "ideal_answer": [ "Somatostatin is a cyclic peptide well known for its strong regulatory effects throughout the body. Also known by the name of growth hormone inhibiting hormone, it is produced in many locations, which include the olfactory bulb, hair follicles, pancreas, retina, and central nervous system (CNS)." ], "exact_answer": [ [ "Hair follicles" ], [ "CNS" ], [ "pancreas" ], [ "olfactory bulb" ], [ "retina" ] ], "type": "list", "id": "5c97f579ecadf2e73f00002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Somatostatin (SST) is a neuromodulator which is abundant throughout the central nervous system (CNS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25777539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Somatostatin (SST) is abundantly produced by the human retina, and the main source is the retinal pigment epithelium (RPE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24627166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Somatostatin (Som), one of the most concentrated neuropeptides in the brain, is highly expressed in the olfactory bulb (OB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The production of somatostatin interneurons in the olfactory bulb is regulated by the transcription factor sp8", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894587", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Somatostatin expression in human hair follicles and its potential role in immune privilege", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23370538", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The kinetics of insulin, glucagon and somatostatin release was studied in human pancreatic islets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19819962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Glucose generates coincident insulin and somatostatin pulses and antisynchronous glucagon pulses from human pancreatic islets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19819962", "endSection": "title" } ] }, { "body": "Is the Philadelphia chromosome a fusion between parts of chromosomes 1 and 9?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29633730", "http://www.ncbi.nlm.nih.gov/pubmed/29435292", "http://www.ncbi.nlm.nih.gov/pubmed/29046997" ], "ideal_answer": [ "No,\nChronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22." ], "exact_answer": "no", "type": "yesno", "id": "5ca10fefecadf2e73f00004a", "snippets": [ { "offsetInBeginSection": 192, "offsetInEndSection": 388, "text": " The Philadelphia chromosome, t(9;22)(q34;q11), is present in 95% of CML patients, resulting in constitutive tyrosine kinase activity; however, ~5% of CML patients possess a Philadelphia variant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29435292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by Philadelphia chromosome which is a balanced translocation between chromosome 9 and 22 in 90% of cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29633730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29046997", "endSection": "abstract" } ] }, { "body": "What is YESCARTA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29501911" ], "ideal_answer": [ "Yescarta is an autologous chimeric antigen receptor (CAR) T cell therapy approved by the FDA. Yescarta\u2122 is approved for the treatment of adult patients with R/R large B cell lymphoma. It is a CD19-specific CAR T cell therapy lysing CD19-positive targets." ], "type": "summary", "id": "5c896ce0d558e5f232000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 442, "text": "Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah\u2122 and Yescarta\u2122) were recently approved by the FDA. Kymriah\u2122 is for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia and Yescarta\u2122 is for the treatment of adult patients with R/R large B cell lymphoma. In common, both are CD19-specific CAR T cell therapies lysing CD19-positive targets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501911", "endSection": "abstract" } ] }, { "body": "What are the 3 types of immunoglobulin heavy chain containing antibodies found in human breast milk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28586632" ], "ideal_answer": [ "IgA, IgG, AND IgM can be found in human milk." ], "exact_answer": [ [ "IgM" ], [ "IgA" ], [ "IgG" ] ], "type": "list", "id": "5c9f79c3ecadf2e73f00003d", "snippets": [ { "offsetInBeginSection": 590, "offsetInEndSection": 887, "text": "This is a descriptive cross-sectional study of a convenience sample of 67 donated colostrum samples at different days after delivery, both raw and pasteurized. Antibody profiles were analyzed at different times during breastfeeding, and total and specific antibodies (IgM, IgA, and IgG subclasses)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28586632", "endSection": "abstract" } ] }, { "body": "What is a exposome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28836271", "http://www.ncbi.nlm.nih.gov/pubmed/28494612", "http://www.ncbi.nlm.nih.gov/pubmed/29676625", "http://www.ncbi.nlm.nih.gov/pubmed/29169635", "http://www.ncbi.nlm.nih.gov/pubmed/29377341" ], "ideal_answer": [ "The exposome is a novel conceptual framework that allows for concurrent examination of multiple intrinsic and extrinsic factors, including environmental exposures, as well as changes in exposures over time, to elucidate the complex environmental factors that affect health outcomes." ], "exact_answer": [ "environmental exposure record" ], "type": "factoid", "id": "5cb0d647ecadf2e73f000059", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28836271", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1109, "text": "The high-throughput and holistic approaches to biomarker discovery used extensively in large-scale molecular epidemiological exposome are also discussed in the context of human exposure to environmental stressors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28494612", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 679, "text": "Experimental data strongly suggests a complex interaction between the exposome (or environmental influences) and genome (genetic material) to produce epigenetic changes (epigenome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29169635", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1307, "text": "Exposome factors including nutrition, medication, occupational factors, pollutants, climatic factors, and psychosocial and lifestyle factors may impact on the course and severity of acne and on treatment efficacy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29377341", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 708, "text": " The exposome is a novel conceptual framework that allows for concurrent examination of multiple intrinsic and extrinsic factors, including environmental exposures, as well as changes in exposures over time, to elucidate the complex environmental factors that affect health outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29676625", "endSection": "abstract" } ] }, { "body": "What does the strimvelis treatment consist of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29625577" ], "ideal_answer": [ "Strimvelis consists of autologous CD34+ cells transduced to express adenosine deaminase [ADA]." ], "exact_answer": [ "autologous CD34+ cells transduced to express adenosine deaminase" ], "type": "factoid", "id": "5c897167d558e5f232000005", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 342, "text": "Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625577", "endSection": "abstract" } ] }, { "body": "Can therapeutic levels of Vedolizumab be found in the breast milk of nursing mothers following treatment for Inflammatory bowel disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28961712" ], "ideal_answer": [ "vedolizumab can be detected in the breast milk of nursing mothers. although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant.", "Vedolizumab is barely detectable in the breast milk of nursing mothers. measurements in breast milk after an infusion of the drug showed that levels did not surpass 480 ng/ml, which was roughly 1/100 of the comparable serum levels.", "Vedolizumab can be detected in the breast milk of nursing mothers .\nAlthough more data are imperative , the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant .", "Vedolizumab can be detected in the breast milk of nursing mothers. Although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant." ], "exact_answer": "no", "type": "yesno", "id": "5c9f7bb6ecadf2e73f00003e", "snippets": [ { "offsetInBeginSection": 1086, "offsetInEndSection": 1351, "text": "Vedolizumab can be detected in the breast milk of nursing mothers. Although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961712", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1356, "text": "Although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961712", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 831, "text": "Results\nVedolizumab was undetectable in breast milk in IBD patients before the first infusion of vedolizumab [n = 3] and in all of the healthy controls [n = 5].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961712", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1076, "text": "However, on serial measurements in breast milk after an infusion, drug levels did not surpass 480 ng/ml, which was roughly 1/100 of the comparable serum levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961712", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1192, "text": "However, on serial measurements in breast milk after an infusion, drug levels did not surpass 480 ng/ml, which was roughly 1/100 of the comparable serum levels.
Conclusions: Vedolizumab can be detected in the breast milk of nursing mothers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961712", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1033, "text": "However, on serial measurements in breast milk after an infusion, drug levels did not surpass 480 ng/ml, which was roughly 1/100 of the comparable serum levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961712", "endSection": "abstract" } ] }, { "body": "What is predicted using SURFY?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30373828" ], "ideal_answer": [ "surfaceome predictor SURFY, based on machine learning." ], "exact_answer": [ "surfaceome predictor" ], "type": "factoid", "id": "5cb0e4a6ecadf2e73f00005b", "snippets": [ { "offsetInBeginSection": 412, "offsetInEndSection": 526, "text": "o enable analysis of the human surfaceome, we developed the surfaceome predictor SURFY, based on machine learning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30373828", "endSection": "abstract" } ] }, { "body": "Which was the first adeno-associated virus vector gene therapy product approved in the United States?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30089698" ], "ideal_answer": [ "The first adeno-associated virus vector gene therapy product in the United States was Luxturna." ], "exact_answer": [ "Luxturna" ], "type": "factoid", "id": "5c897555d558e5f232000009", "snippets": [ { "offsetInBeginSection": 1755, "offsetInEndSection": 2009, "text": "Gene therapy utilizing viral vectors has experienced recent success, culminating in U.S. Food and Drug Administration approval of the first adeno-associated virus vector gene therapy product in the United States: Luxturna for inherited retinal dystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30089698", "endSection": "abstract" } ] }, { "body": "What is known about the gene MIR140?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21576357", "http://www.ncbi.nlm.nih.gov/pubmed/24973690", "http://www.ncbi.nlm.nih.gov/pubmed/28928081" ], "ideal_answer": [ "Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling.\nOur findings showed the novel transcriptional role of miR140-5p in the expression of Nrf2 and miR-140-5p protected against Cisplatin induced oxidative stress by activating Nrf2-dependent antioxidant pathway, providing a potentially therapeutic target in acute kidney injury." ], "type": "summary", "id": "5c8a8f56d558e5f23200000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576357", "endSection": "title" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1456, "text": "These results demonstrate that Mir140 is essential for normal endochondral bone development and suggest that the reduced BMP signaling caused by Dnpep upregulation plays a causal role in the skeletal defects of Mir140-null mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576357", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 902, "text": "Transcripts associated with cartilage development (e.g., Acan, miR140) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24973690", "endSection": "abstract" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 1977, "text": "Our findings showed the novel transcriptional role of miR140-5p in the expression of Nrf2 and miR-140-5p protected against Cisplatin induced oxidative stress by activating Nrf2-dependent antioxidant pathway, providing a potentially therapeutic target in acute kidney injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28928081", "endSection": "abstract" } ] }, { "body": "Which gene therapy treatment is FDA approved for retinal dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30089698" ], "ideal_answer": [ "Luxturna is approved by the Food and Drug Administration (FDA) for the treatment of inherited retinal dystrophy." ], "exact_answer": [ "Luxturna" ], "type": "factoid", "id": "5c89773ed558e5f23200000a", "snippets": [ { "offsetInBeginSection": 1755, "offsetInEndSection": 2010, "text": "Gene therapy utilizing viral vectors has experienced recent success, culminating in U.S. Food and Drug Administration approval of the first adeno-associated virus vector gene therapy product in the United States: Luxturna for inherited retinal dystrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30089698", "endSection": "abstract" } ] }, { "body": "Salivary Cortisol is a biomarker for what disease/syndrome/condition?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25773457", "http://www.ncbi.nlm.nih.gov/pubmed/23969030", "http://www.ncbi.nlm.nih.gov/pubmed/23971022", "http://www.ncbi.nlm.nih.gov/pubmed/27014891", "http://www.ncbi.nlm.nih.gov/pubmed/30488082", "http://www.ncbi.nlm.nih.gov/pubmed/30408721", "http://www.ncbi.nlm.nih.gov/pubmed/28375882", "http://www.ncbi.nlm.nih.gov/pubmed/22812714", "http://www.ncbi.nlm.nih.gov/pubmed/29455296", "http://www.ncbi.nlm.nih.gov/pubmed/21838298", "http://www.ncbi.nlm.nih.gov/pubmed/27686043", "http://www.ncbi.nlm.nih.gov/pubmed/20685855", "http://www.ncbi.nlm.nih.gov/pubmed/23332247", "http://www.ncbi.nlm.nih.gov/pubmed/29747642", "http://www.ncbi.nlm.nih.gov/pubmed/19095358", "http://www.ncbi.nlm.nih.gov/pubmed/23017499" ], "ideal_answer": [ "Salivary cortisone , as a biomarker for psychosocial stress , is associated with state anxiety and heart rate .\nortisol as a stress biomarker", "Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate.", "Salivary Cortisol is a biomarker for stress", "These results suggest that the saliva cortisol level is therefore a useful biomarker to evaluate the stress in AD patients." ], "exact_answer": [ "stress" ], "type": "factoid", "id": "5c9fb428ecadf2e73f000041", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30408721", "endSection": "title" }, { "offsetInBeginSection": 55, "offsetInEndSection": 84, "text": "ortisol as a stress biomarker", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29455296", "endSection": "title" }, { "offsetInBeginSection": 160, "offsetInEndSection": 267, "text": "The salivary cortisol level reflects psychological stress, and it is a good index to assess chronic stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23971022", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1364, "text": "SUMMARY\nSalivary cortisol and cortisone can be used to assess cortisol excess, deficiency and hydrocortisone replacement, with salivary cortisone having the advantage of detection when serum cortisol levels are low and there is no interference from oral hydrocortisone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28375882", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1092, "text": "Salivary cortisone is a superior marker of serum cortisol compared with salivary cortisol, specifically when serum cortisol is low and during hydrocortisone therapy when contamination of saliva may result in misleading salivary cortisol concentrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28375882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Salivary cortisol is frequently used as a biomarker of psychological stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095358", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 893, "text": "The present paper addresses several psychological and biological variables, which may account for such dissociations, and aims to help researchers to rate the validity and psychobiological significance of salivary cortisol as an HPAA biomarker of stress in their experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095358", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 238, "text": "However, psychobiological mechanisms, which trigger the hypothalamus-pituitary-adrenal axis (HPAA) can only indirectly be assessed by salivary cortisol measures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Salivary cortisol as a biomarker in stress research.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095358", "endSection": "title" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1181, "text": "As a biomarker for depression, salivary cortisol VAR demonstrated an optimal cutoff point at 77.8% (AUC=0.94; 95% CI, 0.85-0.98), which is associated with a sensitivity of 82.1% and a specificity of 96.0%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23969030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Salivary cortisol is considered to be a safe and noninvasive measure of hypothalamic-pituitary-adrenal axis functioning, and is a commonly measured biomarker of the human stress response in pediatric research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27686043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "BACKGROUND\nThe aim of this study was to evaluate salivary alpha-amylase (sAA), considered a non-invasive biomarker for sympathetic nervous system (SNS) activity, and salivary cortisol as possible pain-induced stress biomarker,\u00a0in horses with acute abdominal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29747642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Salivary cortisol is commonly used as a clinical biomarker of endocrine status and also as a marker of psychosocial stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23017499", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1385, "text": "CONCLUSION\nSalivary cortisol concentration is positively correlated with occupational stress and increases with the increasing degree of occupational stress, and can be used as an objective biomarker for the identification and evaluation of occupational stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27014891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "PURPOSE\nCortisol is frequently assayed as a stress-responsive biomarker which changes over the course of minutes to meet the demands of a person's social context.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25773457", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 504, "text": "METHODS\nIn 323 children (5-10 years old) participating in the Belgian ChiBS study, salivary cortisol samples, a biomarker for stress, was sampled when waking up, 30 and 60 min after wake up and in the evening on two consecutive weekdays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Cortisol is a classical biomarker for the stress levels of human beings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21838298", "endSection": "abstract" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1769, "text": "Finally, salivary cortisol has been used extensively as a biomarker of stress in a research setting, especially in studies examining psychological stress with repeated measurements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22812714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Salivary cortisol as a biomarker in stress research.Salivary cortisol is frequently used as a biomarker of psychological stress. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095358", "endSection": "title" } ] }, { "body": "What is the function of the cGAS pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28801534", "http://www.ncbi.nlm.nih.gov/pubmed/30395807", "http://www.ncbi.nlm.nih.gov/pubmed/27648547", "http://www.ncbi.nlm.nih.gov/pubmed/29169058", "http://www.ncbi.nlm.nih.gov/pubmed/27902332", "http://www.ncbi.nlm.nih.gov/pubmed/28137885", "http://www.ncbi.nlm.nih.gov/pubmed/28940468", "http://www.ncbi.nlm.nih.gov/pubmed/28920955", "http://www.ncbi.nlm.nih.gov/pubmed/26944200" ], "ideal_answer": [ "The cGAS-STING pathway not only mediates protective immune defense against infection by a large variety of DNA-containing pathogens but also detects tumor-derived DNA and generates intrinsic antitumor immunity." ], "exact_answer": [ "Immune defense" ], "type": "factoid", "id": "5c8aa082d558e5f23200000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Cyclic di-AMP (c-di-AMP) is a bacterial signaling nucleotide synthesized by several human pathogens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29169058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Cyclic GMP-AMP synthase (cGAS) has recently been identified as the primary protein that detects cytosolic double stranded DNA to invoke a type I interferon response. The cGAS pathway is vital in the recognition of DNA encoded viruses as well as self-DNA leaked from the nucleus of damaged cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30395807", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1053, "text": "These results indicate that activation of the cGAS pathway is important for intrinsic antitumor immunity and that cGAMP may be used directly for cancer immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28137885", "endSection": "abstract" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1019, "text": " this work identifies long DNA as the molecular entity stimulating the cGAS pathway upon cytosolic DNA challenge such as viral infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28801534", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1155, "text": "these data suggest that inactivation of the cGAS pathway plays a critical role in tumour progression, and reveal a direct link between hypoxia-responsive miRNAs and adaptive immune responses to the hypoxic tumour microenvironment, thus unveiling potential new therapeutic strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28920955", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 306, "text": "dysregulation of the cGAS pathway is linked to autoimmune diseases while targeted stimulation may be of benefit in immunoncology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28940468", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 510, "text": "The cGAS-STING pathway not only mediates protective immune defense against infection by a large variety of DNA-containing pathogens but also detects tumor-derived DNA and generates intrinsic antitumor immunity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27648547", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1052, "text": "our data indicate that the cGAS-STING pathway plays a role in the surveillance of HBV infection and may be exploited for development of novel anti-HBV strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27902332", "endSection": "abstract" } ] }, { "body": "Does RUNX2 inhibit astrocyte differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27546532" ], "ideal_answer": [ "No, RUNX2 promostes astrocyte differentiation." ], "exact_answer": "no", "type": "yesno", "id": "5c8fe71b0101eac87000000b", "snippets": [ { "offsetInBeginSection": 610, "offsetInEndSection": 886, "text": "The method was able to recapitulate experimentally validated cell-fate determinants, and validation of two predicted cell-fate determinants confirmed that overexpression of ESR1 and RUNX2 in mouse neural stem cells induces neuronal and astrocyte differentiation, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27546532", "endSection": "abstract" } ] }, { "body": "What are 5 key questions in human performance modeling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22005615", "http://www.ncbi.nlm.nih.gov/pubmed/29531424" ], "ideal_answer": [ "There are five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are.", "the five key questions of human performance modeling: 1) why we build models of human performance; 2) what the expectations of a good human performance model are; 3) what the procedures and requirements in building and verifying a human performance model are; 4) how we integrate a human performance model with system design; and 5) what the possible future directions of human performance modeling research are.", "the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are.", "the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are" ], "exact_answer": [ [ "Why build models?" ], [ "What are the expectations of a good model?" ], [ "What are the procedures and requirements?" ], [ "How do we integrate a model with system design?" ], [ "What are the future directions of Human performance modeling?" ] ], "type": "list", "id": "5c9fb583ecadf2e73f000042", "snippets": [ { "offsetInBeginSection": 254, "offsetInEndSection": 667, "text": "the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29531424", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 666, "text": "This paper describes and summarizes the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29531424", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 614, "text": "We conducted a systematic review of the literature to address 5 key questions specific to this population: 1) What are the current national clinical practice recommendations and guidelines for depression screening; 2) What are the prevalence and predictors of screening; 3) How well do screening tools detect depression; 4) Does screening lead to diagnosis, treatment, and improved outcomes; and 5) What are the most effective treatment methods?", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22005615", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 719, "text": "This paper describes and summarizes the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29531424", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 982, "text": "We conducted a systematic review of the literature to address 5 key questions specific to this population: 1) What are the current national clinical practice recommendations and guidelines for depression screening; 2) What are the prevalence and predictors of screening; 3) How well do screening tools detect depression; 4) Does screening lead to diagnosis, treatment, and improved outcomes; and 5) What are the most effective treatment methods?
METHODS: We searched bibliographic databases for full-length articles published in English between 1990 and 2010 that addressed at least 1 of our key questions.
RESULTS: We identified 5 clinical practice guidelines pertinent to question 1, and 12 systematic reviews or post-hoc analyses of pooled data that addressed questions 3 through 5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22005615", "endSection": "abstract" } ] }, { "body": "What is the mode of action of the Tc toxins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24572368", "http://www.ncbi.nlm.nih.gov/pubmed/28233068", "http://www.ncbi.nlm.nih.gov/pubmed/30232455", "http://www.ncbi.nlm.nih.gov/pubmed/11286884", "http://www.ncbi.nlm.nih.gov/pubmed/27571177", "http://www.ncbi.nlm.nih.gov/pubmed/23870259", "http://www.ncbi.nlm.nih.gov/pubmed/15679840" ], "ideal_answer": [ "The toxin complex (tc) genes of bacteria comprise a large and growing family whose mode of action remains obscure. Tc toxins are widely distributed among different gram-negative and gram-positive bacteria, where they act as pathogenicity factors. Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood." ], "type": "summary", "id": "5c98fcf0ecadf2e73f00002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Tc toxins secrete toxic enzymes into host cells using a unique syringe-like injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA forms the translocation channel and the TcB-TcC heterodimer functions as a cocoon that shields the toxic enzyme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30232455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The toxin complex (tc) genes of Photorhabdus encode insecticidal, high molecular weight Tc toxins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11286884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The toxin complex (tc) genes of bacteria comprise a large and growing family whose mode of action remains obscure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15679840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Tc toxins are widely distributed among different gram-negative and gram-positive bacteria, where they act as pathogenicity factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23870259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24572368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Tc toxins from pathogenic bacteria use a special syringe-like mechanism to perforate the host cell membrane and inject a deadly enzyme into the host cytosol. The molecular mechanism of this unusual injection system is poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Various bacterial toxins have potent insecticidal activity. Recently, the Toxin complexes (Tc's) of Photorhabdus and Xenorhabdus species have become an increased focus of current research.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28233068", "endSection": "abstract" } ] }, { "body": "What does RUNX2 stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19121369" ], "ideal_answer": [ "Runt related factor-2" ], "exact_answer": [ "Runt related factor-2" ], "type": "factoid", "id": "5c8fe7cb0101eac87000000c", "snippets": [ { "offsetInBeginSection": 367, "offsetInEndSection": 396, "text": "Runt related factor-2 (Runx2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19121369", "endSection": "abstract" } ] }, { "body": "Where, in the body, would the Cobb-Stainsby excision arthroplasty be performed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29413774" ], "ideal_answer": [ "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy ( Stainsby ) with extensor tendon transfer to the metatarsal head ( Cobb ) .", "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb)", "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb).", "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer" ], "exact_answer": [ "foot" ], "type": "factoid", "id": "5c9ff25eecadf2e73f000043", "snippets": [ { "offsetInBeginSection": 131, "offsetInEndSection": 274, "text": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413774", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 272, "text": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413774", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 280, "text": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413774", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 261, "text": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413774", "endSection": "abstract" } ] }, { "body": "Are cardenolides inhibitors of Na+/K+ ATPase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30053394", "http://www.ncbi.nlm.nih.gov/pubmed/30372816", "http://www.ncbi.nlm.nih.gov/pubmed/29683473" ], "ideal_answer": [ "Yes,\nCardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells." ], "exact_answer": "yes", "type": "yesno", "id": "5c9906dcecadf2e73f00002f", "snippets": [ { "offsetInBeginSection": 257, "offsetInEndSection": 493, "text": ". Previously, we reported that a variety of cardenolides impart anti-transmissible gastroenteritis coronavirus (TGEV) activity in swine testicular (ST) cells, through targeting of the cell membrane sodium/potassium pump, Na+/K+-ATPase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053394", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1092, "text": ": We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ /K+ -ATPases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29683473", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 490, "text": "Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30372816", "endSection": "abstract" } ] }, { "body": "Can antisense threapy be used for Huntington's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22726826" ], "ideal_answer": [ "Yes, antisense oligonucleotide therapy has been shown to lower Huntingtin mRNA levels and be beneficial against Huntington's disease." ], "exact_answer": "yes", "type": "yesno", "id": "5c900779ecadf2e73f000001", "snippets": [ { "offsetInBeginSection": 89, "offsetInEndSection": 290, "text": "In this issue of Neuron, Kordasiewicz et\u00a0al. (2012) show the benefit of transient antisense oligonucleotide (ASO) therapy to degrade Huntingtin mRNA and elicit sustained therapeutic benefit in HD mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "\"Huntingtin holiday\": progress toward an antisense therapy for Huntington's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22726826", "endSection": "title" } ] }, { "body": "What are acoustic reported genes used to detect?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29300010" ], "ideal_answer": [ "Acoustic reporter genes are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound.", "acoustic reporter genes , which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound ,", "Here we introduce acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound", "Here we introduce acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound,", "acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound," ], "type": "summary", "id": "5ca9f932ecadf2e73f000054", "snippets": [ { "offsetInBeginSection": 526, "offsetInEndSection": 659, "text": "acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29300010", "endSection": "abstract" } ] }, { "body": "What is a lipin 1 protein doing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30092116", "http://www.ncbi.nlm.nih.gov/pubmed/30028636", "http://www.ncbi.nlm.nih.gov/pubmed/29457836" ], "ideal_answer": [ "As a lipin family founding member, lipin1 exerts dual functions as a phosphatidate phosphatase enzyme and/or a co-transcriptional regulator in lipid metabolism. In fact, it is also involved in many other cell processes." ], "type": "summary", "id": "5ca3bfd7ecadf2e73f00004b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Lipin 1 regulates glycerolipid homeostasis by acting as a phosphatidic acid phosphohydrolase (PAP) enzyme in the triglyceride-synthesis pathway and by regulating transcription factor activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30028636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "As a lipin family founding member, lipin1 exerts dual functions as a phosphatidate phosphatase enzyme and/or a co-transcriptional regulator in lipid metabolism. In fact, it is also involved in many other cell processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30092116", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1409, "text": "lipogenic regulator lipin 1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29457836", "endSection": "abstract" } ] }, { "body": "Which company produces patisiran?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30251172" ], "ideal_answer": [ "Patisiran has been developed by Alnylam Pharmaceuticals." ], "exact_answer": [ "Alnylam Pharmaceuticals" ], "type": "factoid", "id": "5c900b9eecadf2e73f000004", "snippets": [ { "offsetInBeginSection": 426, "offsetInEndSection": 722, "text": "Patisiran has been developed by Alnylam Pharmaceuticals; it was recently approved in the USA for the treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis (hATTR) in adults and subsequently approved in the EU for the treatment of hATTR in adults with stage 1 or 2 polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30251172", "endSection": "abstract" } ] }, { "body": "What protein is recruited by Crumbs to regulate tracheal development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21172808", "http://www.ncbi.nlm.nih.gov/pubmed/25065756" ], "ideal_answer": [ "In Drosophila, stellate-shaped tracheal terminal cells make seamless tubes, Early endocytosis maintains normal steady-state levels of Crumbs, which recruits apical phosphorylated (active) Moesin (Moe), which in turn regulates seamless tube shape in the development of the trachea." ], "exact_answer": [ "moesin (Moe)" ], "type": "factoid", "id": "5caa0247ecadf2e73f000055", "snippets": [ { "offsetInBeginSection": 1144, "offsetInEndSection": 1320, "text": "We propose that early endocytosis maintains normal steady-state levels of Crumbs, which recruits apical phosphorylated (active) Moe, which in turn regulates seamless tube shape", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25065756", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 962, "text": "There, Crb, acting in parallel with the epidermal growth factor receptor (Egfr) pathway, is required for tracheal cell apical constriction and for organising an actomyosin complex, which we propose is mediated by Crb recruitment of moesin (Moe).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21172808", "endSection": "abstract" } ] }, { "body": "Is collagen matrix of human articular cartilage changing with disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27384346", "http://www.ncbi.nlm.nih.gov/pubmed/18991091", "http://www.ncbi.nlm.nih.gov/pubmed/20488735" ], "ideal_answer": [ "No,\nThe collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease." ], "exact_answer": "no", "type": "yesno", "id": "5ca5127eecadf2e73f00004c", "snippets": [ { "offsetInBeginSection": 943, "offsetInEndSection": 1110, "text": "The collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27384346", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1164, "text": "the chondrocytes in ageing articular cartilage have limited capacity to turnover the interterritorial matrix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Type II collagen is a major component of articular cartilage and its breakdown is a key feature of osteoarthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20488735", "endSection": "abstract" } ] }, { "body": "Is ustekinumab a polyclonal antibody?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29164954" ], "ideal_answer": [ "Ustekinumab is a human monoclonal IgG1 antibody targeting the p40-subunit shared by interleukin (IL)12 and IL-23." ], "exact_answer": "no", "type": "yesno", "id": "5c9162b5ecadf2e73f00000e", "snippets": [ { "offsetInBeginSection": 5, "offsetInEndSection": 177, "text": "Ustekinumab, a human monoclonal IgG1 antibody targeting the p40-subunit shared by interleukin (IL)12 and IL-23, represents a potential treatment for atopic dermatitis (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29164954", "endSection": "abstract" } ] }, { "body": "Where in the body, is ghrelin secreted?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24806082", "http://www.ncbi.nlm.nih.gov/pubmed/17101319", "http://www.ncbi.nlm.nih.gov/pubmed/21035199", "http://www.ncbi.nlm.nih.gov/pubmed/19009647", "http://www.ncbi.nlm.nih.gov/pubmed/22231739", "http://www.ncbi.nlm.nih.gov/pubmed/15648018", "http://www.ncbi.nlm.nih.gov/pubmed/17646723", "http://www.ncbi.nlm.nih.gov/pubmed/19129426", "http://www.ncbi.nlm.nih.gov/pubmed/18350524", "http://www.ncbi.nlm.nih.gov/pubmed/26019019", "http://www.ncbi.nlm.nih.gov/pubmed/27376422", "http://www.ncbi.nlm.nih.gov/pubmed/12176667", "http://www.ncbi.nlm.nih.gov/pubmed/17983856", "http://www.ncbi.nlm.nih.gov/pubmed/29392854", "http://www.ncbi.nlm.nih.gov/pubmed/12352514", "http://www.ncbi.nlm.nih.gov/pubmed/17096064", "http://www.ncbi.nlm.nih.gov/pubmed/16254526", "http://www.ncbi.nlm.nih.gov/pubmed/17251274" ], "ideal_answer": [ "Ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa.", "Ghrelin , an orexigenic peptide , is secreted from endocrine cells in the gastric mucosa .", "BACKGROUND: Ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa.", "ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa." ], "exact_answer": [ "stomach" ], "type": "factoid", "id": "5caa06d0ecadf2e73f000056", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 99, "text": "Ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29392854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Ghrelin is a recently described hormone secreted by the stomach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15648018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND\nGhrelin is secreted mainly in the stomach and plays a role in food intake regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22231739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND\nGhrelin is a body weight-regulating peptide produced and secreted primarily by the gastric mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17096064", "endSection": "abstract" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1935, "text": "These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12176667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Ghrelin is a 28-amino acid peptide secreted mainly by the stomach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19129426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19009647", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 515, "text": "Most of the ghrelin produced in the body is secreted in the stomach, but it is also expressed in the hypothalamus, pituitary, pancreas, intestine, kidney, heart and gonads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18350524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "OBJECTIVES\nGhrelin, a recently discovered hormone mainly secreted by the stomach, has several metabolic functions including regulation of food intake, energy homeostasis and body weight.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "PURPOSE\nGhrelin is mainly secreted from the stomach and plays a role in appetite, weight gain, and the promotion of a positive energy balance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26019019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Ghrelin, the only known orexigenic gut hormone, is secreted mainly from the stomach, increases with fasting and before meal initiation in humans and rats, and increases food intake after central or peripheral administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17251274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Ghrelin is a peptide hormone produced and secreted in the stomach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21035199", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 392, "text": "Ghrelin secreted by the stomach stimulates the afferent vagus nerve and promotes food intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17983856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "BACKGROUND & AIMS\nGhrelin is secreted by the stomach and stimulates food intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17101319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Ghrelin is a gut peptide composed of 28 amino acids mostly secreted in the gastric fundus mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27376422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "BACKGROUND\nA wide variety of functions has been attributed to ghrelin, a peptide hormone secreted in the stomach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24806082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "OBJECTIVE\nGhrelin is a hormone secreted mainly in the stomach which stimulates appetite and food intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17646723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Ghrelin and feedback systems.Ghrelin is produced primarily in the stomach in response to hunger, and circulates in the blood. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17983856", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "BACKGROUND: Ghrelin is a body weight-regulating peptide produced and secreted primarily by the gastric mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17096064", "endSection": "abstract" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1939, "text": "These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.
", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12176667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "BACKGROUND: Ghrelin is secreted by the stomach, the hypothalamus, and the placenta in humans and has growth hormone-secreting and orexigenic properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12352514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Ghrelin is secreted by the stomach, the hypothalamus, and the placenta in humans and has growth hormone-secreting and orexigenic properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12352514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Ghrelin is a body weight-regulating peptide produced and secreted primarily by the gastric mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17096064", "endSection": "abstract" } ] }, { "body": "List the ERM proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29777033", "http://www.ncbi.nlm.nih.gov/pubmed/29311472", "http://www.ncbi.nlm.nih.gov/pubmed/29329782" ], "ideal_answer": [ "ezrin\nradixin\nmoesin" ], "exact_answer": [ [ "ezrin" ], [ "radixin" ], [ "moesin" ] ], "type": "list", "id": "5ca64b5becadf2e73f000051", "snippets": [ { "offsetInBeginSection": 423, "offsetInEndSection": 458, "text": "ezrin/radixin/moesin (ERM) proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29329782", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 531, "text": "ezrin, radixin and moesin (ERM proteins)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29311472", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 240, "text": "Ezrin/radixin/moesin (ERM) proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29777033", "endSection": "abstract" } ] }, { "body": "What is epitranscriptomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29671387" ], "ideal_answer": [ "Epitranscriptomics is the fast expanding area of RNA modifications." ], "type": "summary", "id": "5c922bc3ecadf2e73f000013", "snippets": [ { "offsetInBeginSection": 1047, "offsetInEndSection": 1191, "text": "Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29671387", "endSection": "abstract" } ] }, { "body": "What is resistin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29937317", "http://www.ncbi.nlm.nih.gov/pubmed/24780007", "http://www.ncbi.nlm.nih.gov/pubmed/18417718", "http://www.ncbi.nlm.nih.gov/pubmed/26729407", "http://www.ncbi.nlm.nih.gov/pubmed/23981771", "http://www.ncbi.nlm.nih.gov/pubmed/15103228", "http://www.ncbi.nlm.nih.gov/pubmed/30353146", "http://www.ncbi.nlm.nih.gov/pubmed/19024936", "http://www.ncbi.nlm.nih.gov/pubmed/12660880", "http://www.ncbi.nlm.nih.gov/pubmed/18191042", "http://www.ncbi.nlm.nih.gov/pubmed/29278852", "http://www.ncbi.nlm.nih.gov/pubmed/14962997", "http://www.ncbi.nlm.nih.gov/pubmed/19095472", "http://www.ncbi.nlm.nih.gov/pubmed/14644422", "http://www.ncbi.nlm.nih.gov/pubmed/27079485" ], "ideal_answer": [ "The adipocyte-secreting adipokine, resistin, may play a critical role in the modulation of inflammatory diseases.", "Resistin, a pro-inflammatory cytokine," ], "exact_answer": [ "adipokine" ], "type": "factoid", "id": "5c840782617e120c34000006", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 800, "text": "Resistin, a pro-inflammatory cytokine, is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29278852", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 394, "text": "Leptin, adiponectin, and resistin are the most studied adipokines which play important roles in the regulation of cardiovascular homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29278852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Resistin is a recently discovered hormone that is exclusively expressed in adipose tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12660880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Resistin is a secreted adipose tissue hormone that belongs to the resistin-like molecule family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14644422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Resistin is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18417718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "OBJECTIVES\nResistin is an adipocytokine that has been related to inflammation and insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24780007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Resistin, an adipocyte-secreted factor, is known to be elevated in breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26729407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Resistin is an adipokine that induces insulin resistance in mice; serum concentrations are decreased by fasting and increased by feeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18191042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Resistin is an adipose-derived hormone that has been proposed as a link among obesity, insulin resistance, and diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14962997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The adipokine resistin has been proposed to link obesity, insulin resistance and diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30353146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "OBJECTIVE\nResistin is a secreted factor that is elevated in rheumatoid arthritis (RA) and believed to drive joint inflammation in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19095472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Resistin is a circulating mediator of insulin resistance mainly expressed in human monocytes and responsive to inflammatory stimuli.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23981771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "BACKGROUND\nResistin is an immunometabolic mediator that is elevated in several inflammatory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29937317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Pituitary resistin gene expression: effects of age, gender and obesity.Resistin is a new adipocytokine which is expressed in rat, mouse and possibly human adipose tissue. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15103228", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 278, "text": "Leptin belongs to the adipokine family, which also contains adiponectin and resistin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19024936", "endSection": "abstract" } ] }, { "body": "Is Pim-1 a protein phosphatase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29399171", "http://www.ncbi.nlm.nih.gov/pubmed/29355758" ], "ideal_answer": [ "No,\nPim-1 is a kinase and not a phosphatase." ], "exact_answer": "no", "type": "yesno", "id": "5cb37f76ecadf2e73f00005c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Pim-1 proto-oncogene, serine/threonine kinase (PIM-1) phosphorylates a series of substrates to exert its oncogenic function in numerous malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29399171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The Pim1 serine/threonine kinase is associated with multiple cellular functions including proliferation, survival, differentiation, apoptosis, tumorigenesis, immune regulation and inflammation in vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29355758", "endSection": "abstract" } ] }, { "body": "Name three binding partners of cofilin 2.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25373779", "http://www.ncbi.nlm.nih.gov/pubmed/19752190", "http://www.ncbi.nlm.nih.gov/pubmed/28886070" ], "ideal_answer": [ "Cofilin 2 can bind miR-201a, the protein 14-3-3, and ATP/ADP-Pi-actin filaments." ], "exact_answer": [ [ "miR-301a" ], [ "14-3-3" ], [ "ATP/ADP-Pi-actin filaments" ] ], "type": "list", "id": "5c9007460101eac870000012", "snippets": [ { "offsetInBeginSection": 459, "offsetInEndSection": 642, "text": "Cofilin-2 (Cfl2) was identified as one of the potential targets of miR-301a using prediction databases, which we validated by luciferase assay and mutation of predicted binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28886070", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 738, "text": "In contrast to other isoforms, cofilin-2 efficiently binds and disassembles both ADP- and ATP/ADP-Pi-actin filaments. We mapped surface-exposed cofilin-2-specific residues required for ATP-actin binding and propose that these residues function as an \"actin nucleotide-state sensor\" among ADF/cofilins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25373779", "endSection": "abstract" } ] }, { "body": "What is the function of GvpA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28898511", "http://www.ncbi.nlm.nih.gov/pubmed/7683649", "http://www.ncbi.nlm.nih.gov/pubmed/22580065", "http://www.ncbi.nlm.nih.gov/pubmed/1282192", "http://www.ncbi.nlm.nih.gov/pubmed/9094221", "http://www.ncbi.nlm.nih.gov/pubmed/25648404", "http://www.ncbi.nlm.nih.gov/pubmed/22941504" ], "ideal_answer": [ "The gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC, and", "The gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC, and seven additional accessory proteins are also involved.", "Gas vesicles are proteinaceous, gas-filled nanostructures produced by some bacteria and archaea. The hydrophobic major structural protein GvpA forms the ribbed gas vesicle wall.", "The gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC,", "the gas vesicle wall is solely formed of proteins with the two major components, gvpa and gvpc," ], "exact_answer": [ "GvpA forms the gas vesicle wall" ], "type": "factoid", "id": "5ca9f846ecadf2e73f000053", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Gas vesicles are proteinaceous, gas-filled nanostructures produced by some bacteria and archaea. The hydrophobic major structural protein GvpA forms the ribbed gas vesicle wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28898511", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 898, "text": " The gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25648404", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 345, "text": "The wall of these gas vesicles is freely permeable to gas molecules and is composed of a small hydrophobic protein, GvpA, which forms a single-layer wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22941504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Gas vesicles are intracellular, microbial flotation devices that consist of mainly one protein, GvpA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9094221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Modeling of the major gas vesicle protein, GvpA: from protein sequence to vesicle wall structure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22580065", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 364, "text": "Gas vesicle production and the expression of the gvpA gene encoding the major gas vesicle protein, GvpA, was monitored in each Haloferax volcanii transformant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1282192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Analysis of gas vesicle gene expression in Haloferax mediterranei reveals that GvpA and GvpC are both gas vesicle structural proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7683649", "endSection": "title" } ] }, { "body": "What is a SMR based BCI?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21436515", "http://www.ncbi.nlm.nih.gov/pubmed/30414824", "http://www.ncbi.nlm.nih.gov/pubmed/24835634", "http://www.ncbi.nlm.nih.gov/pubmed/30063219", "http://www.ncbi.nlm.nih.gov/pubmed/29075937", "http://www.ncbi.nlm.nih.gov/pubmed/26891350", "http://www.ncbi.nlm.nih.gov/pubmed/25147518", "http://www.ncbi.nlm.nih.gov/pubmed/24080080", "http://www.ncbi.nlm.nih.gov/pubmed/26736445" ], "ideal_answer": [ "Many Brain Computer Interface (BCI) and neurofeedback studies have investigated the impact of sensorimotor rhythm (SMR)", "An SMR based BCI is a SensoriMotor Rhythm Based brain-Computer Interface (BCI). It is an alternative communication system between the human brain and an output device and is controlled by a sensorimotor rhythm (SMR), a type of brain wave." ], "type": "summary", "id": "5c521c8c7e3cb0e231000007", "snippets": [ { "offsetInBeginSection": 395, "offsetInEndSection": 458, "text": " sensorimotor rhythm-based brain-computer interfaces (SMR-BCI) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29075937", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 403, "text": "Here, we studied the immediate and therapeutic effects of BCI-based training to control pre-movement sensorimotor rhythm (SMR) amplitude on robot-assisted finger extension in people with stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30063219", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 482, "text": " Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26891350", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 119, "text": "Brain Computer Interface (BCI) and neurofeedback studies have investigated the impact of sensorimotor rhythm (SMR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30414824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Modulation of sensorimotor rhythms (SMR) was suggested as a control signal for brain-computer interfaces (BCI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25147518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Sensorimotor rhythm (SMR) based Brain-Computer Interfaces (BCI) typically require lengthy user training.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26736445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "All brain-computer interface (BCI) groups that have published results of studies involving a large number of users performing BCI control based on the voluntary modulation of sensorimotor rhythms (SMR) report that BCI control could not be achieved by a non-negligible number of subjects (estimated 20% to 25%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21436515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "OBJECTIVE\nConnect-Four, a new sensorimotor rhythm (SMR) based brain-computer interface (BCI) gaming application, was evaluated by four severely motor restricted end-users; two were in the locked-in state and had unreliable eye-movement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24080080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "OBJECTIVE\nIt is well known that to acquire sensorimotor (SMR)-based brain-computer interface (BCI) control requires a training period before users can achieve their best possible performances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24835634", "endSection": "abstract" } ] }, { "body": "Is myc a tumour suppressor gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28430012", "http://www.ncbi.nlm.nih.gov/pubmed/27880072", "http://www.ncbi.nlm.nih.gov/pubmed/27532209", "http://www.ncbi.nlm.nih.gov/pubmed/28833404" ], "ideal_answer": [ "No,\r\nMyc is a proto-oncogene." ], "exact_answer": "no", "type": "yesno", "id": "5cb38a56ecadf2e73f00005e", "snippets": [ { "offsetInBeginSection": 255, "offsetInEndSection": 374, "text": "oncogenic Myc, a master transcription factor that turns on anabolic metabolism to promote cell growth in many cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27532209", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 649, "text": "he MYC oncogene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27880072", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 686, "text": " the proto-oncogene protein c-MYC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430012", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 188, "text": "however, other genes such as the proto-oncogene c-Myc are promising targets for anticancer therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28833404", "endSection": "abstract" } ] }, { "body": "Which syndrome is associated to SAMHD1 gene mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29583030" ], "ideal_answer": [ "Mutations in the SAMHD1 gene that cause the severe autoimmune disease, Aicardi-Goutieres syndrome (AGS)." ], "exact_answer": [ "Aicardi-Goutieres syndrome" ], "type": "factoid", "id": "5c93e8bdecadf2e73f00001c", "snippets": [ { "offsetInBeginSection": 211, "offsetInEndSection": 413, "text": "Its emerging role as an effector of innate immunity is affirmed by mutations in the SAMHD1 gene that cause the severe autoimmune disease, Aicardi-Goutieres syndrome (AGS) and that are linked to cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29583030", "endSection": "abstract" } ] }, { "body": "List proteins with RING domain.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29471350", "http://www.ncbi.nlm.nih.gov/pubmed/29432170", "http://www.ncbi.nlm.nih.gov/pubmed/29367421", "http://www.ncbi.nlm.nih.gov/pubmed/29107100", "http://www.ncbi.nlm.nih.gov/pubmed/29324855", "http://www.ncbi.nlm.nih.gov/pubmed/29320607", "http://www.ncbi.nlm.nih.gov/pubmed/29187402", "http://www.ncbi.nlm.nih.gov/pubmed/29295817", "http://www.ncbi.nlm.nih.gov/pubmed/29426838" ], "ideal_answer": [ "RING1\nTRIM proteins\nTRAF6 \nUHRF1\nMARCH7\nSINA\nBRCA1" ], "exact_answer": [ [ "RING1" ], [ "TRIM proteins" ], [ "TRAF6" ], [ "UHRF1" ], [ "MARCH7" ], [ "SINA" ], [ "BRCA1" ] ], "type": "list", "id": "5c990afbecadf2e73f000030", "snippets": [ { "offsetInBeginSection": 512, "offsetInEndSection": 581, "text": " The RING domain of RING1 was required for its E3 Ub ligase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29187402", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 398, "text": " The TRIM proteins are classically characterized by the presence of an amino-terminal RING domain and a B-box domain followed by a coiled coil domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29107100", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 311, "text": "the detailed mechanism by which the TRAF6 RING dimer promotes ubiquitin transfer was unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432170", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "RING ubiquitin E3 ligases enclose a RING domain for ubiquitin ligase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29324855", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 935, "text": " UHRF1 RING domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29471350", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 336, "text": " MARCH7, a RING domain-containing ubiquitin E3 ligase,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29295817", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Seven in absentia (SINA) protein is one subgroup of ubiquitin ligases possessing an N-terminal cysteine-rich really interesting new gene (RING) domain,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29320607", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 179, "text": "The BRCA1 RING domain is a ubiquitin ligase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29367421", "endSection": "abstract" } ] }, { "body": "What conditions are associated with mutations in the gene FAAH?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22442717", "http://www.ncbi.nlm.nih.gov/pubmed/20942817", "http://www.ncbi.nlm.nih.gov/pubmed/22912404", "http://www.ncbi.nlm.nih.gov/pubmed/12060782", "http://www.ncbi.nlm.nih.gov/pubmed/20098695", "http://www.ncbi.nlm.nih.gov/pubmed/10764768", "http://www.ncbi.nlm.nih.gov/pubmed/27327781" ], "ideal_answer": [ "Human FAAH gene mutations are associated with increased body weight and obesity. Results suggest that genetic mutations in FAAH may constitute important risk factors for problem drug use and support a potential link between functional abnormalities in the endogenous cannabinoid system and drug abuse and dependence.\nresearch on the genetic modulation of pain has already identified variants in these genes, relative to pain, which may facilitate the pharmacogenetic assessments of new analgesics." ], "type": "summary", "id": "5c9d170cecadf2e73f000032", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 225, "text": "FAAH (fatty acid amide hydrolase), primarily expressed in the liver, hydrolyzes the endocannabinoids fatty acid ethanolamides (FAA). Human FAAH gene mutations are associated with increased body weight and obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22442717", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 225, "text": "Human FAAH gene mutations are associated with increased body weight and obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22442717", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 161, "text": "whereas mutations in FAAH are associated with obesity in humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22912404", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1162, "text": "Collectively, these results suggest that genetic mutations in FAAH may constitute important risk factors for problem drug use and support a potential link between functional abnormalities in the endogenous cannabinoid system and drug abuse and dependence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12060782", "endSection": "abstract" }, { "offsetInBeginSection": 1817, "offsetInEndSection": 2082, "text": "This is the first study to document that FAAH 385 A mutant alleles have a direct effect on elevated plasma levels of anandamide and related NAEs in humans. These biomarkers may indicate risk for severe obesity and may suggest novel ECS obesity treatment strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20098695", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1769, "text": "nerve growth factor (NGFB), its tyrosine kinase receptor (NTRK1) and the fatty acid amide hydrolase (FAAH) have become targets of interest. For most of these genes, functional variants have been associated with neuro-psychiatric disorders and not yet with analgesia. However, research on the genetic modulation of pain has already identified variants in these genes, relative to pain, which may facilitate the pharmacogenetic assessments of new analgesics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20942817", "endSection": "abstract" } ] }, { "body": "What is the results of mutations in the gene autoimmune regulator?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29427825", "http://www.ncbi.nlm.nih.gov/pubmed/29437776", "http://www.ncbi.nlm.nih.gov/pubmed/29150834", "http://www.ncbi.nlm.nih.gov/pubmed/29666621" ], "ideal_answer": [ "Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene (AIRE)" ], "exact_answer": [ "Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)" ], "type": "factoid", "id": "5cb39707ecadf2e73f000060", "snippets": [ { "offsetInBeginSection": 296, "offsetInEndSection": 456, "text": "a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29150834", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 559, "text": "The crucial role played by AIRE in central immune tolerance emerged in the studies on the pathogenesis of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy, a rare inherited polyendocrine/autoimmune disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29427825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Autoimmune polyendocrine syndrome type 1 (APS-1; OMIM #240300), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29437776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene (AIRE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29666621", "endSection": "abstract" } ] }, { "body": "Is CD63 an exosomal marker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28346015", "http://www.ncbi.nlm.nih.gov/pubmed/28770472", "http://www.ncbi.nlm.nih.gov/pubmed/28819811" ], "ideal_answer": [ "Yes,\nCD63 is a exosomal marker" ], "exact_answer": "yes", "type": "yesno", "id": "5cb3a2dd99d1e53537000001", "snippets": [ { "offsetInBeginSection": 701, "offsetInEndSection": 746, "text": "f exosome marker proteins (e.g., CD63, Alix) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28770472", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 513, "text": " CD63 levels and acetylcholinesterase (AChE) activity were used as markers of exosome,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28819811", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 475, "text": " The results demonstrated these exosomes all expressed CD9, CD63, CD81, Alix", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346015", "endSection": "abstract" } ] }, { "body": "Is subdural empyema a complication of sinusitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16462969", "http://www.ncbi.nlm.nih.gov/pubmed/12402493", "http://www.ncbi.nlm.nih.gov/pubmed/7810468", "http://www.ncbi.nlm.nih.gov/pubmed/17182345", "http://www.ncbi.nlm.nih.gov/pubmed/9217340", "http://www.ncbi.nlm.nih.gov/pubmed/30014307", "http://www.ncbi.nlm.nih.gov/pubmed/12521560", "http://www.ncbi.nlm.nih.gov/pubmed/28806018", "http://www.ncbi.nlm.nih.gov/pubmed/25437686", "http://www.ncbi.nlm.nih.gov/pubmed/16777239", "http://www.ncbi.nlm.nih.gov/pubmed/29404826", "http://www.ncbi.nlm.nih.gov/pubmed/9951090", "http://www.ncbi.nlm.nih.gov/pubmed/12172943", "http://www.ncbi.nlm.nih.gov/pubmed/22030191", "http://www.ncbi.nlm.nih.gov/pubmed/29682134", "http://www.ncbi.nlm.nih.gov/pubmed/29131135" ], "ideal_answer": [ "Yes, subdural empyema can be a complication of sinusitis" ], "exact_answer": "yes", "type": "yesno", "id": "5ca0c81eecadf2e73f000047", "snippets": [ { "offsetInBeginSection": 19, "offsetInEndSection": 180, "text": "Acute and chronic sinusitis can give rise to a wide array of intracranial and orbital complications. These complications include brain abscess, subdural empyema,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29404826", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 323, "text": " A computed tomography scan showed bilateral paranasal sinus disease, and magnetic resonance imaging showed a right frontal abscess and subdural empyema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29682134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Frontal sinusitis complicated by a brain abscess and subdural empyema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29682134", "endSection": "title" }, { "offsetInBeginSection": 204, "offsetInEndSection": 292, "text": "In older children, sinusitis and otitis media are usually the source for subdural empyem", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30014307", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Subdural empyema as a complication of sinusitis in the pediatric population.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16777239", "endSection": "title" }, { "offsetInBeginSection": 2077, "offsetInEndSection": 2182, "text": "Second, subdural empyema appears to arise in the setting of subacute rather than acute frontal sinusitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16777239", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 514, "text": "Subdural empyema is a rare but potentially life-threatening complication following paranasal sinusitis and should be considered as a neurological emergency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29131135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "[Subdural empyema as a complication of sinusitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951090", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "INTRODUCTION\nSubdural empyema is an uncommon but serious complication of sinusitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12172943", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 318, "text": "Intracranial subdural empyema is most frequently a complication of sinusitis or, less frequently, otitis or neurosurgical procedures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12521560", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 471, "text": "Subdural empyema is a rare complication of sinusitis although very severe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12402493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Subdural empyema is a rare complication of sinusitis in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16462969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Subdural empyema is a rare but serious complication of paranasal sinusitis which may result in death or permanent disability in a significant proportion of cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9217340", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 850, "text": "We report a case of subdural empyema secondary to frontal sinusitis in an otherwise healthy immunocompetent adolescent boy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22030191", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 309, "text": "Subdural empyema is a rare but life-threatening complication of paranasal sinusitis, otitis media, or mastoid disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28806018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Wolf in Sheep's Clothing Subdural Empyema: A Rare Complication of Acute Sinusitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28806018", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Interhemispheric and Infratentorial Subdural Empyema with Preseptal Cellulitis as Complications of Sinusitis: A Case Report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29131135", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Subdural empyema as a complication of sinusitis in the pediatric population.Sinusitis is a rare cause of intracranial infection in children. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16777239", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "[Subdural empyema as a complication of sinusitis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951090", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 335, "text": "Intracranial subdural empyema is most frequently a complication of sinusitis or, less frequently, otitis or neurosurgical procedures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12521560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Streptococcus pluranimalium: A novel human pathogen?We present the first case of a subdural empyema caused by Streptococcus pluranimalium, in a healthy adolescent male as a possible complication of subclinical frontal sinusitis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437686", "endSection": "title" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1283, "text": "The diagnosis of subdural empyema as a complication of asymptomatic sinusitis in an immunocompetent patient with no history of fever or upper respiratory symptoms was unanticipated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25437686", "endSection": "abstract" }, { "offsetInBeginSection": 2329, "offsetInEndSection": 2434, "text": "Second, subdural empyema appears to arise in the setting of subacute rather than acute frontal sinusitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16777239", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Bifrontal decompressive craniectomy for acute subdural empyema.Subdural empyema is an uncommon but serious complication of sinusitis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12172943", "endSection": "title" }, { "offsetInBeginSection": 482, "offsetInEndSection": 638, "text": "Subdural empyema is a rare but potentially life-threatening complication following paranasal sinusitis and should be considered as a neurological emergency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29131135", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 530, "text": "We present a patient with subdural empyema in whom the diagnosis was delayed, followed by a discussion of suppurative complications of sinusitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17182345", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 607, "text": "We report an unusual case of sinusitis-associated acute subdural empyema in a 13-year-old patient, presenting in a catastrophic manner with acutely raised intracranial pressure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12172943", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 475, "text": "The symptoms of subdural empyema may be mild and may be the same as those associated with sinusitis, or the infection may result in alteration of the level of consciousness and focal neurologic deficits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7810468", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 335, "text": "We report the clinical and radiological course of an adolescent with a subdural empyema secondary to sinusitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16462969", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 602, "text": "We report two cases of subdural empyema secondary to sinusitis in persons without impaired immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Subdural empyema as a complication of sinusitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951090", "endSection": "title" }, { "offsetInBeginSection": 102, "offsetInEndSection": 246, "text": "Furthermore, subdural empyema usually is related to sinus infections, particularly those caused by Streptococcus milleri, an anaerobic organism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Subdural empyema is an uncommon but serious complication of sinusitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12172943", "endSection": "abstract" } ] }, { "body": "What is aphasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26999324", "http://www.ncbi.nlm.nih.gov/pubmed/28691196" ], "ideal_answer": [ "Aphasia is an inability to comprehend or formulate language because of damage to specific brain regions." ], "type": "summary", "id": "5c9fb2aaecadf2e73f00003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Aphasia, the language disorder following brain damage, is frequently accompanied by deficits of working memor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26999324", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 82, "text": "People with aphasia (PWA) use pantomime, gesture in absence of speech,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28691196", "endSection": "abstract" } ] }, { "body": "Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium, yes or no", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29398602", "http://www.ncbi.nlm.nih.gov/pubmed/30217516" ], "ideal_answer": [ "Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium and causes anaplasmosis", "The genus Anaplasma belonging to the Anaplasmataceae family (order Rickettsiales) comprises obligate intracellular Gram-negative bacteria of veterinary and public health importance. nov." ], "exact_answer": "yes", "type": "yesno", "id": "5c98ac7fecadf2e73f00002b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "The genus Anaplasma belonging to the Anaplasmataceae family (order Rickettsiales) comprises obligate intracellular Gram-negative bacteria of veterinary and public health importance. Six species and five types of strains genetically related are currently assigned to the genus Anaplasma including Anaplasma marginale, A. centrale, A. bovis, A. phagocytophilum, A. ovis and A. platys as classified species, and \"A. capra\", A. odocolei sp. nov.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29398602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick-borne illness, is caused by a gram-negative obligate intracellular bacterium Anaplasma phagocytophilum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30217516", "endSection": "abstract" } ] }, { "body": "What is the role of Acyl-Homoserine Lactone in bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28887424", "http://www.ncbi.nlm.nih.gov/pubmed/30352386", "http://www.ncbi.nlm.nih.gov/pubmed/27896412", "http://www.ncbi.nlm.nih.gov/pubmed/29130184", "http://www.ncbi.nlm.nih.gov/pubmed/26989738", "http://www.ncbi.nlm.nih.gov/pubmed/12426339", "http://www.ncbi.nlm.nih.gov/pubmed/19464950" ], "ideal_answer": [ "A number of bacteria use a class of chemical compounds called acyl-homoserine lactones (AHLs) as quorum sensing (QS) signals to coordinate their behavior at the population level, including pathogens like Pseudomonas aeruginosa.", "Some bacteria use a class of chemical compounds called acyl-homoserine lactones (AHLs) as quorum sensing (QS) signals to coordinate their behavior at the population level.", "tructural analogues of acyl homoserine lactones with Quorum Sensing antagonist activity." ], "type": "summary", "id": "5c979383ecadf2e73f000027", "snippets": [ { "offsetInBeginSection": 173, "offsetInEndSection": 261, "text": "tructural analogues of acyl homoserine lactones with Quorum Sensing antagonist activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30352386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "A number of bacteria use a class of chemical compounds called acyl-homoserine lactones (AHLs) as quorum sensing (QS) signals to coordinate their behavior at the population level", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29130184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "OBJECTIVE\nBacterial colonization relies on communication between bacteria via so-called \"quorum-sensing molecules\", which include the acyl-homoserine lactone group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27896412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "BACKGROUND\nN-Acyl homoserine lactone (AHL) is found to be the main component of quorum sensing (QS) in Gram-negative bacteria and plays an important role in biofilm formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26989738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Diverse Gram-negative bacteria communicate with each other by using diffusible N-acyl-homoserine lactone (AHL) signaling molecules to coordinate gene expression with cell population density.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The genomes of many bacteria that participate in nitrogen cycling through the process of nitrification contain putative genes associated with acyl-homoserine lactone (AHL) quorum sensing (QS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Many proteobacteria use acyl-homoserine lactones as quorum-sensing signals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12426339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Bacterial colonization relies on communication between bacteria via so-called quorum-sensing molecules, which include the acyl-homoserine lactone group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27896412", "endSection": "abstract" } ] }, { "body": "List 3 indications for rituximab.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27603326", "http://www.ncbi.nlm.nih.gov/pubmed/28633733", "http://www.ncbi.nlm.nih.gov/pubmed/23735074", "http://www.ncbi.nlm.nih.gov/pubmed/28185174", "http://www.ncbi.nlm.nih.gov/pubmed/23700188", "http://www.ncbi.nlm.nih.gov/pubmed/29606668", "http://www.ncbi.nlm.nih.gov/pubmed/28536935", "http://www.ncbi.nlm.nih.gov/pubmed/30358861" ], "ideal_answer": [ "Rituximab is used to treat rheumatoid arthritis as well as poly- and dermatomyositis, chronic lymphocytic leukemia, juvenile idiopathic arthritis, and Pemphigus foliaceus (PF)." ], "exact_answer": [ [ "Rheumatoid arthritis" ], [ "Chronic Lymphocytic Leukemia" ], [ "poly- and dermatomyositis" ], [ "juvenile idiopathic arthritis" ], [ "Pemphigus foliaceus" ] ], "type": "list", "id": "5c961281ecadf2e73f000021", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 272, "text": "o assess clinical outcomes including imaging findings on computed tomography (CT), pulmonary function testing (PFT), and glucocorticoid (GC) use in patients with the antisynthetase syndrome (AS) and interstitial lung disease (ILD) treated with rituximab (RTX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29606668", "endSection": "abstract" }, { "offsetInBeginSection": 1805, "offsetInEndSection": 1892, "text": " RIX is the preferred off-label biologic drug for poly- and dermatomyositis in Germany.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28536935", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 141, "text": "Rituximab (RTX) may be a treatment option for children and young people with JIA, although it is not licensed for this indication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30358861", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 98, "text": " rituximab in children and young people with juvenile idiopathic arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30358861", "endSection": "title" }, { "offsetInBeginSection": 79, "offsetInEndSection": 285, "text": "chronic lymphocytic leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28185174", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 349, "text": "rituximab's efficacy has been well-documented in adults with refractory PF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28633733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Rituximab in the management of juvenile pemphigus foliaceus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28633733", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "BACKGROUND\nRituximab is a chimeric, anti-CD20 monoclonal antibody registered for the treatment of B-cell malignancies and refractory rheumatoid arthritis in Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23735074", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 709, "text": "Currently, rituximab is only FDA-approved for treatment of follicular and diffuse large B-cell non-Hodgkin's lymphoma, rheumatoid arthritis, chronic lymphocytic leukemia, granulomatosis with polyangiitis (formerly Wegener's granulomatosis) and microscopic polyangiitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27603326", "endSection": "abstract" }, { "offsetInBeginSection": 1831, "offsetInEndSection": 2116, "text": "In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23700188", "endSection": "abstract" } ] }, { "body": "Is the crystal structure of Pim-1 available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25575657", "http://www.ncbi.nlm.nih.gov/pubmed/30033129", "http://www.ncbi.nlm.nih.gov/pubmed/16227208", "http://www.ncbi.nlm.nih.gov/pubmed/22339127", "http://www.ncbi.nlm.nih.gov/pubmed/15808862", "http://www.ncbi.nlm.nih.gov/pubmed/23936194", "http://www.ncbi.nlm.nih.gov/pubmed/22926267" ], "ideal_answer": [ "Yes,\nThe crystal structures of Pim1 in apo form and bound with AMPPNP have been solved" ], "exact_answer": "yes", "type": "yesno", "id": "5cb380b8ecadf2e73f00005d", "snippets": [ { "offsetInBeginSection": 505, "offsetInEndSection": 673, "text": "Recent crystallographic studies of Pim-1 have identified unique structural features but have not provided insight into how the kinase recognizes its target substrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16227208", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 454, "text": "a co-crystal structure of lead molecule (HS38) in complex with DAPK3, a dual Pim/DAPK3 inhibitor (HS56)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30033129", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 425, "text": "The crystal structure of this compound with PIM1 confirmed the predicted binding mode and protein-ligand interactions except those in the acidic ribose pocket. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25575657", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 690, "text": "Using the determined X-ray crystal structure of PIM1 complexed to the compound 1-R as a control, we discuss the importance of including the protein flexibility inherent in the ensemble docking protocol, for the accuracy of the structure prediction of the bound state. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22926267", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 530, "text": "Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23936194", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 211, "text": "Crystallographic and docking data analyses have been undertaken using inhibitor complexes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22339127", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 459, "text": "The crystal structures of Pim1 in apo form and bound with AMPPNP have been solved", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15808862", "endSection": "abstract" } ] }, { "body": "Do tumour-associated macrophages have a prognostic role in gliomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28767130" ], "ideal_answer": [ "M2-like TAMs hold an unfavourable prognostic value in high-grade gliomas and may contribute to a pro-tumourigenic microenvironment." ], "exact_answer": "yes", "type": "yesno", "id": "5c92159becadf2e73f000012", "snippets": [ { "offsetInBeginSection": 67, "offsetInEndSection": 340, "text": "Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double immunofluorescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28767130", "endSection": "abstract" }, { "offsetInBeginSection": 1659, "offsetInEndSection": 1932, "text": "This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold an unfavourable prognostic value in high-grade gliomas and may contribute to a pro-tumourigenic microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28767130", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1330, "text": "Our data revealed that the amount of especially CD204+ TAMs increases with malignancy grade. In grade III-IV, high CD204 expression was associated with shorter survival, while high IBA-1 intensity correlated with a longer survival. In grade IV, CD204 showed independent prognostic value when adjusting for clinical data and the methylation status of O6-methylguanine-DNA methyltransferase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28767130", "endSection": "abstract" } ] }, { "body": "Is TNF-\u03b1 an activator of pancreatic stellate cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24089530", "http://www.ncbi.nlm.nih.gov/pubmed/20689058" ], "ideal_answer": [ "Yes,\nTNF-\u03b1 is the prime factor responsible for the activation of pancreatic stellate cells." ], "exact_answer": "yes", "type": "yesno", "id": "5c9f0dabecadf2e73f00003b", "snippets": [ { "offsetInBeginSection": 825, "offsetInEndSection": 910, "text": "TNF-\u03b1 is the prime factor responsible for the activation of pancreatic stellate cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24089530", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 735, "text": "Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1\u03b2, TNF-\u03b1, PDGF-BB, and IFN-\u03b3, but not TGF-\u03b21. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20689058", "endSection": "abstract" } ] }, { "body": "Can mitochondria transfer from cell to cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29158129", "http://www.ncbi.nlm.nih.gov/pubmed/29357914" ], "ideal_answer": [ "Yes,\nthe recently discovered phenomenon of mitochondrial transfer between mammalian cells has gained momentum since it was first described in cell culture systems more than a decade ago." ], "exact_answer": "yes", "type": "yesno", "id": "5c9e738decadf2e73f000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Interest in the recently discovered phenomenon of mitochondrial transfer between mammalian cells has gained momentum since it was first described in cell culture systems more than a decade ago.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29158129", "endSection": "abstract" }, { "offsetInBeginSection": 2055, "offsetInEndSection": 2160, "text": "We show evidence that mitochondria transfer from Jurkat cells to MSCs, which is mediated by cell adhesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29357914", "endSection": "abstract" }, { "offsetInBeginSection": 1589, "offsetInEndSection": 1721, "text": "This process of mitochondria transfer is mediated by tunneling nanotubes, which are protrusions that extend from the cell membrane .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29357914", "endSection": "abstract" } ] }, { "body": "Can Enlimomab improve stroke outcomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19849665", "http://www.ncbi.nlm.nih.gov/pubmed/12365824", "http://www.ncbi.nlm.nih.gov/pubmed/9693236", "http://www.ncbi.nlm.nih.gov/pubmed/12038658", "http://www.ncbi.nlm.nih.gov/pubmed/9744839", "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "http://www.ncbi.nlm.nih.gov/pubmed/11692032" ], "ideal_answer": [ "No. Anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke and, indeed, may significantly worsen stroke outcome." ], "exact_answer": "no", "type": "yesno", "id": "5e44c33a48dab47f26000020", "snippets": [ { "offsetInBeginSection": 1772, "offsetInEndSection": 2068, "text": "Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19849665", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 351, "text": "The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12365824", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 696, "text": "en classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12038658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND AND PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "title" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1358, "text": "ESULTS: At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1630, "text": "CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1636, "text": "CONCLUSIONS\n\nThe authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1362, "text": "There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1037, "text": "RESULTS\n\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1246, "text": "The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1524, "text": "However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9744839", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1357, "text": "There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1797, "offsetInEndSection": 1974, "text": "These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1037, "text": "RESULTS\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" }, { "offsetInBeginSection": 1934, "offsetInEndSection": 2069, "text": "Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19849665", "endSection": "abstract" }, { "offsetInBeginSection": 1284, "offsetInEndSection": 1505, "text": "CONCLUSIONS\nDoses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9693236", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 176, "text": "PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 1791, "offsetInEndSection": 1968, "text": "These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 1739, "offsetInEndSection": 1916, "text": "These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11692032", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1590, "text": "The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11673584", "endSection": "abstract" } ] }, { "body": "What is the Triad of Alport Syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7699956", "http://www.ncbi.nlm.nih.gov/pubmed/8357522", "http://www.ncbi.nlm.nih.gov/pubmed/21141008", "http://www.ncbi.nlm.nih.gov/pubmed/24398087", "http://www.ncbi.nlm.nih.gov/pubmed/30957516", "http://www.ncbi.nlm.nih.gov/pubmed/8545576", "http://www.ncbi.nlm.nih.gov/pubmed/29873249", "http://www.ncbi.nlm.nih.gov/pubmed/23165304" ], "ideal_answer": [ "Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations." ], "exact_answer": [ [ "nephritic syndrome" ], [ "sensorineural deafness" ], [ "ophthalmological alterations" ] ], "type": "list", "id": "5e31b575fbd6abf43b00004c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "PURPOSE: Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29873249", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 501, "text": "Classical AS is a progressive renal disease presenting with a triad of progressive hematuric nephritis and typical extra-renal complications, such as sensorineural hearing loss (SNHL) and variable ocular anomalies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24398087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "In 1927, Arthur C. Alport first published his description of a triad of symptoms in a family with hereditary congenital haemorrhagic nephritis, deafness and ocular changes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23165304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "BACKGROUND: Alport syndrome refers to the clinical triad of hereditary nephritis, sensorineural deafness, and ocular abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8545576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Alport syndrome is an oculo-renal syndrome characterized by a triad of clinical findings consisting of hemorrhagic nephritis, sensorineural hearing loss and characteristic ocular findings. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21141008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND\n\nAlport syndrome is an inherited Type IV collagenopathy characterised by renal failure, hearing loss and ophthalmic manifestations such as lenticonus and dot-and-fleck retinopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30957516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "PURPOSE:\n\nAlport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29873249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "BACKGROUND\n\nAlport syndrome refers to the clinical triad of hereditary nephritis, sensorineural deafness, and ocular abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8545576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "BACKGROUND Alport syndrome refers to the clinical triad of hereditary nephritis, sensorineural deafness, and ocular abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8545576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Alport syndrome is an oculo-renal syndrome characterized by a triad of clinical findings consisting of hemorrhagic nephritis, sensorineural hearing loss and characteristic ocular findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21141008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "In 1927, Arthur C. Alport first published his description of a triad of symptoms in a family with hereditary congenital haemorrhagic nephritis, deafness and ocular changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23165304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Epstein 's triad which is a syndrome with the combination of macrothrombocytopenia , deafness and nephritis , is similar to Alport 's syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7699956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "The Alport 's syndrome is a disease characterized by a symptomatic triad: nephropathy , hypoacusia and ocular alterations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8357522", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 174, "text": "Alport first published his description of a triad of symptoms in a family with hereditary congenital haemorrhagic nephritis , deafness and ocular changes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23165304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Alport syndrome refers to the clinical triad of hereditary nephritis , sensorineural deafness , and ocular abnormalities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8545576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND\nAlport syndrome is an inherited Type IV collagenopathy characterised by renal failure, hearing loss and ophthalmic manifestations such as lenticonus and dot-and-fleck retinopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30957516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "PURPOSE:\nAlport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29873249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Alport syndrome is an oculo-renal syndrome characterized by a triad of clinical findings consisting of hemorrhagic nephritis, sensorineural hearing loss and characteristic ocular findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21141008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "PURPOSE:: Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29873249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "BACKGROUND: Alport syndrome refers to the clinical triad of hereditary nephritis, sensorineural deafness, and ocular abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8545576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Alport syndrome refers to the clinical triad of hereditary nephritis, sensorineural deafness, and ocular abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8545576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29873249", "endSection": "abstract" } ] }, { "body": "Does GRHL2 over-expression lead to EMT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26355710", "http://www.ncbi.nlm.nih.gov/pubmed/26887977", "http://www.ncbi.nlm.nih.gov/pubmed/27402864", "http://www.ncbi.nlm.nih.gov/pubmed/28960866", "http://www.ncbi.nlm.nih.gov/pubmed/23814079", "http://www.ncbi.nlm.nih.gov/pubmed/23284647", "http://www.ncbi.nlm.nih.gov/pubmed/28067907" ], "ideal_answer": [ "Grainyhead-like 2 (Grhl2), a transcription factor, has been reported to be associated with several tumor processes including EMT. Grhl2 antagonizes transforming growth factor-b (TGFb)-induced EMT", "The transcription factor--Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype. Grhl2 is a suppressor of EMT. Grhl2 antagonizes transforming growth factor-b (TGFb)-induced EMT.", "The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in various developmental processes Grhl2 antagonizes transforming growth factor-b (TGFb)-induced EMT" ], "exact_answer": "no", "type": "yesno", "id": "5d384ce87bc3fee31f000013", "snippets": [ { "offsetInBeginSection": 562, "offsetInEndSection": 720, "text": "Grhl2 is down-regulated in disseminated cancer cells that have undergone EMT, and over-expression of Grhl2 is sufficient to induce epithelial gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23284647", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1360, "text": " Grhl2 plays an essential role in the determination of epithelial phenotype of breast cancers, EMT and tumor progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23284647", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 955, "text": "In breast cancer cell lines, shRNA-mediated knockdown of GRHL2 expression or functional inactivation of GRHL2 using dominant negative GRHL2 proteins induces down-regulation of ERBB3 gene expression, a striking reduction in cell proliferation, and morphological and phenotypical alterations characteristic of an epithelial-to-mesenchymal transition (EMT), thus implying contradictory roles of GRHL2 in breast carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23814079", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1312, "text": "Interestingly, we could further demonstrate that expression of GRHL2 is directly suppressed by the transcription factor zinc finger enhancer-binding protein 1 (ZEB1), which in turn is a direct target for repression by GRHL2, suggesting that the EMT transcription factors GRHL2 and ZEB1 form a double negative regulatory feedback loop in breast cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23814079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Mesenchymal-Epithelial Transition in Sarcomas Is Controlled by the Combinatorial Expression of MicroRNA 200s and GRHL2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27402864", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 341, "text": "transcription factor--Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26887977", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 262, "text": "We explored the role of grainyhead-like 2 (GRHL2), a suppressor of EMT, in the progression of PDAC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960866", "endSection": "abstract" }, { "offsetInBeginSection": 878, "offsetInEndSection": 1009, "text": "GRHL2 knockdown CFPAC-1 cells demonstrated morphological changes into mesenchymal appearances and reduced proliferation through EMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in various developmental processes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26355710", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 378, "text": "Grainyhead-like 2 (Grhl2), a transcription factor, has been reported to be associated with several tumor processes including EMT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28067907", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1022, "text": "Grhl2 antagonizes transforming growth factor-\u03b2 (TGF\u03b2)-induced EMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28067907", "endSection": "abstract" } ] }, { "body": "What is Intanza?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23442585" ], "ideal_answer": [ "Intanza(r) 9 ug (sanofi pasteur) is a microneedle-delivered intradermal trivalent inactivated influenza vaccine approved in 2009 for the prevention of seasonal influenza in adults 18 to 59 years of age. The microneedle system reliably and reproducibly delivers the vaccine to the dermis. Clinical studies show that Intanza 9 ug is as immunogenic and as well tolerated in working-age adults as a reference intramuscular trivalent inactivated vaccine. Local reactions to Intanza 9 ug, mainly erythema, are transient, mostly mild or moderate, and do not affect acceptability. Intanza 9 ug is considered satisfactory by at least 95% of both vaccinees and prescribers, especially because of the short needle and rapid administration." ], "type": "summary", "id": "5e7f5eaa835f4e4777000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Intanza (\u00ae) 9 \u00b5g intradermal seasonal influenza vaccine for adults 18 to 59 years of age.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23442585", "endSection": "title" }, { "offsetInBeginSection": 126, "offsetInEndSection": 852, "text": "Intanza\u00ae 9 \u00b5g (sanofi pasteur) is a microneedle-delivered intradermal trivalent inactivated influenza vaccine approved in 2009 for the prevention of seasonal influenza in adults 18 to 59 years of age. The microneedle system reliably and reproducibly delivers the vaccine to the dermis. Clinical studies show that Intanza 9 \u00b5g is as immunogenic and as well tolerated in working-age adults as a reference intramuscular trivalent inactivated vaccine. Local reactions to Intanza 9 \u00b5g, mainly erythema, are transient, mostly mild or moderate, and do not affect acceptability. Intanza 9 \u00b5g is considered satisfactory by at least 95% of both vaccinees and prescribers, especially because of the short needle and rapid administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23442585", "endSection": "abstract" } ] }, { "body": "Is the Fluzone intradermal and the Fluzone intradermal quadrivalent vaccine produced by different companies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27457797" ], "ideal_answer": [ "No, the Fluzone Intradermal vaccine and the Fluzone Intradermal Quadrivalent vaccine are produced by Sanofi Pasteur." ], "exact_answer": "no", "type": "yesno", "id": "5e7f5cc5835f4e4777000015", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 569, "text": "An intradermal version of Fluzone\u00ae split-virion inactivated trivalent influenza vaccine, containing 9\u00a0\u00b5g hemagglutinin per strain of A/H1N1, A/H3N2, and one B lineage virus (Fluzone Intradermal, Sanofi Pasteur), became available in the US during the 2011-2012 influenza season for adults 18-64\u00a0years of age. In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9\u00a0\u00b5g hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27457797", "endSection": "abstract" } ] }, { "body": "What is the purpose of the Barricaid annular closure device?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27169045", "http://www.ncbi.nlm.nih.gov/pubmed/30115053", "http://www.ncbi.nlm.nih.gov/pubmed/23429676", "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "http://www.ncbi.nlm.nih.gov/pubmed/27879508", "http://www.ncbi.nlm.nih.gov/pubmed/29075906", "http://www.ncbi.nlm.nih.gov/pubmed/27236580", "http://www.ncbi.nlm.nih.gov/pubmed/23473658" ], "ideal_answer": [ "Barricaid annular closure device can improve outcome after lumbar discectomy by reducing the risk of recurrent disc herniation of the same level." ], "type": "summary", "id": "5e3aab25b5b409ea5300001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "We report the unusual case of a young patient with reoperation after annuloplasty using the Barricaid\u00ae (Intrinsic Therapeutics, Woburn, MA, USA) closure device. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29075906", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 663, "text": "Annular closure devices such as the Barricaid system aim to improve outcome after lumbar discectomy by reducing the risk of recurrent disc herniation of the same level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29075906", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 555, "text": "Several prosthesis and techniques to reduce re-herniation have been proposed including implantation of an annular closure device (ACD) - Barricaid\u2122 and an annular tissue repair system (AR) - Anulex-Xclose\u2122. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30115053", "endSection": "abstract" }, { "offsetInBeginSection": 1693, "offsetInEndSection": 1905, "text": "CONCLUSION: Early results showed the use of Barricaid and Anulex devices are beneficial for short term outcomes demonstrating reduction in symptomatic disc reherniation with low post-operative complication rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30115053", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 474, "text": "PRESENTATION OF CASE: We present a clinical case of a patient with transpedicular and interbody fixation reoperation after annuloplasty with Barricaid closure device. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27236580", "endSection": "abstract" }, { "offsetInBeginSection": 1732, "offsetInEndSection": 1988, "text": "ONCLUSIONS: Implantation of a novel annular repair device was associated with greater maintenance of disk height and improved 1-year leg pain, back pain, and low-back disability. Recurrent disk herniation did not occur in any patient after annular repair. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27879508", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 529, "text": "his study investigated whether implantation with the Barricaid annular closure device (ACD) during discectomy reduced the rate of facet degeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473658", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1108, "text": "Patients implanted with Barricaid had significantly reduced rates and grades of facet degeneration than patients without Barricaid. Reinforcing the annulus fibrosus with Barricaid during lumbar discectomy may slow the progression of facet joint degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Use of Annular Closure Device (Barricaid\u00ae) for Preventing Lumbar Disc Reherniation: One-Year Results of Three Cases", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27169045", "endSection": "title" }, { "offsetInBeginSection": 137, "offsetInEndSection": 339, "text": "The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Multicenter study of lumbar discectomy with Barricaid annular closure device for prevention of lumbar disc reherniation in US patients: A historically controlled post-market study protocol.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "title" }, { "offsetInBeginSection": 459, "offsetInEndSection": 674, "text": "DESIGN AND METHODS\n\nThis is a historically controlled post-market multicenter study to determine the safety and efficacy of the Barricaid device when used in addition to primary lumbar discectomy in a US population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 475, "text": "PRESENTATION OF CASE\n\nWe present a clinical case of a patient with transpedicular and interbody fixation reoperation after annuloplasty with Barricaid closure device.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27236580", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 744, "text": "The aim of this article is to demonstrate the opportunities of surgical treatment of patients with lumbar disc herniation involving annuloplasty using the Barricaid closure device as the final stage and the ways to resolve possible complications requiring reoperation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27236580", "endSection": "abstract" }, { "offsetInBeginSection": 1960, "offsetInEndSection": 2017, "text": "The Barricaid seems to prevent nucleus from reherniating.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23429676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Use of Annular Closure Device (Barricaid\u00ae) for Preventing Lumbar Disc Reherniation: One-Year Results of Three Cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27169045", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Effect of an Annular Closure Device (Barricaid) on Same-Level Recurrent Disk Herniation and Disk Height Loss After Primary Lumbar Discectomy: Two-year Results of a Multicenter Prospective Cohort Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27879508", "endSection": "title" }, { "offsetInBeginSection": 494, "offsetInEndSection": 662, "text": "Annular closure devices such as the Barricaid system aim to improve outcome after lumbar discectomy by reducing the risk of recurrent disc herniation of the same level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29075906", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 338, "text": "The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 671, "text": "Annular closure devices such as the Barricaid system aim to improve outcome after lumbar discectomy by reducing the risk of recurrent disc herniation of the same level", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29075906", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 549, "text": "Several prosthesis and techniques to reduce re-herniation have been proposed including implantation of an annular closure device ( ACD ) - Barricaid\u2122 and an annular tissue repair system ( AR ) - Anulex-Xclose", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30115053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Multicenter study of lumbar discectomy with Barricaid annular closure device for prevention of lumbar disc reherniation in US patients: A historically controlled post-market study protocol", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Effect of an Annular Closure Device ( Barricaid ) on Same-Level Recurrent Disk Herniation and Disk Height Loss After Primary Lumbar Discectomy: Two-year Results of a Multicenter Prospective Cohort Study", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27879508", "endSection": "title" }, { "offsetInBeginSection": 126, "offsetInEndSection": 327, "text": "The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Use of Annular Closure Device ( Barricaid\u00ae ) for Preventing Lumbar Disc Reherniation: One-Year Results of Three Cases", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27169045", "endSection": "title" }, { "offsetInBeginSection": 136, "offsetInEndSection": 339, "text": "The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 674, "text": "DESIGN AND METHODS\nThis is a historically controlled post-market multicenter study to determine the safety and efficacy of the Barricaid device when used in addition to primary lumbar discectomy in a US population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 899, "text": "A total of 75 patients with large annular defects will receive the Barricaid device following lumbar discectomy at up to 25 sites in the US and will return for clinical and imaging follow-up at 4 weeks, 3 months, and 1 year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 531, "text": "This study investigated whether implantation with the Barricaid annular closure device (ACD) during discectomy reduced the rate of facet degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473658", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 327, "text": "The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 542, "text": "Several prosthesis and techniques to reduce re-herniation have been proposed including implantation of an annular closure device (ACD) - Barricaid\u2122 and an annular tissue repair system (AR) - Anulex-Xclose\u2122.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30115053", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 866, "text": "A total of 75 patients with large annular defects will receive the Barricaid device following lumbar discectomy at up to 25 sites in the US and will return for clinical and imaging follow-up at 4 weeks, 3 months, and 1 year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31464935", "endSection": "abstract" } ] }, { "body": "What disease is associated with mutations in the MECP2 transcription factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27200222", "http://www.ncbi.nlm.nih.gov/pubmed/28337123", "http://www.ncbi.nlm.nih.gov/pubmed/29431277", "http://www.ncbi.nlm.nih.gov/pubmed/27782879", "http://www.ncbi.nlm.nih.gov/pubmed/25769649", "http://www.ncbi.nlm.nih.gov/pubmed/28143937", "http://www.ncbi.nlm.nih.gov/pubmed/15345242", "http://www.ncbi.nlm.nih.gov/pubmed/25634725", "http://www.ncbi.nlm.nih.gov/pubmed/20504995", "http://www.ncbi.nlm.nih.gov/pubmed/17997046", "http://www.ncbi.nlm.nih.gov/pubmed/22297041", "http://www.ncbi.nlm.nih.gov/pubmed/29078406", "http://www.ncbi.nlm.nih.gov/pubmed/24916645", "http://www.ncbi.nlm.nih.gov/pubmed/27428650", "http://www.ncbi.nlm.nih.gov/pubmed/22865604", "http://www.ncbi.nlm.nih.gov/pubmed/24399845", "http://www.ncbi.nlm.nih.gov/pubmed/19349604", "http://www.ncbi.nlm.nih.gov/pubmed/15549394" ], "ideal_answer": [ "mutations in the methyl-cpg-binding protein-2 gene (mecp2) are commonly associated with rett syndrome", "Mutations in the MECP2 transcription factor, which codes for the transcription factor ECE1, have been found to be associated with Rett syndrome.", "Mutations in the methyl-CpG-binding protein-2 gene (MECP2) are commonly associated with Rett syndrome. Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT).", "Mutations in the methyl-CpG-binding protein-2 gene (MECP2) are commonly associated with Rett syndrome.", "Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT).", "Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding the methyl-CpG-binding protein MeCP2 on the X chromosome", "Mutations in the MECP2 transcription factor, which encodes the cellular iron exporter ferroportin, are associated with Rett syndrome." ], "exact_answer": [ "Rett syndrome" ], "type": "factoid", "id": "5e6157cb1af46fc13000000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Mutations in the methyl-CpG-binding protein-2 gene (MECP2) are commonly associated with Rett syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29431277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding the methyl-CpG-binding protein MeCP2 on the X chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28143937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27782879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Rett syndrome is a severe neurodevelopmental disorder mainly caused by mutations in the transcriptional regulator MeCP2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20504995", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 229, "text": "Mutations in the MeCP2 gene cause Rett syndrome, a progressive neurodevelopmental disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27200222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Rett syndrome (RTT) is a debilitating neurological disorder caused by mutations in the gene encoding the transcription factor Methyl CpG Binding Protein 2 (MECP2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29078406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Rett syndrome (RTT) is associated with mutations in the transcriptional repressor gene MeCP2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17997046", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 228, "text": "Mutations in the MeCP2 gene cause Rett syndrome, a progressive neurodevelopmental disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27200222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24399845", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Rett syndrome (RTT), the second most common cause of mental retardation in females, has been associated with mutations in MeCP2, the archetypical member of the methyl-CpG binding domain (MBD) family of proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15549394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Rett syndrome (RTT) is a severe neurodevelopmental disease caused by mutations in methyl-CpG-binding protein 2 (MECP2), which encodes a transcriptional modulator of many genes including BDNF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25634725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "BACKGROUND\n\nRett syndrome (RTT) is caused by mutations in the transcriptional repressor methyl CpG-binding protein 2 (MECP2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19349604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27428650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Mutations in the gene encoding the methyl-CpG-binding protein MECP2 are the major cause of Rett syndrome , an autism spectrum disorder mainly affecting young females . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22865604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Rett syndrome ( RTT ) is a severe neurodevelopmental disorder with features of autism that results from mutation of the gene encoding the transcriptional repressor methyl-CpG binding protein ( MECP2) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15345242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations affecting the neural transcription factor MeCP2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25769649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28337123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding the transcription factor methyl-CpG-binding protein 2 (MeCP2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22297041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Rett syndrome is a monogenic disease due to de novo mutations in either MECP2 or CDKL5 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24916645", "endSection": "abstract" } ] }, { "body": "Is endotrophin derived from collagen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29175445", "http://www.ncbi.nlm.nih.gov/pubmed/30246318", "http://www.ncbi.nlm.nih.gov/pubmed/29229941" ], "ideal_answer": [ "Yes,\nEndotrophin is released from COL VI." ], "exact_answer": "yes", "type": "yesno", "id": "5e821ac5835f4e4777000031", "snippets": [ { "offsetInBeginSection": 735, "offsetInEndSection": 779, "text": "endotrophin production from type IV collagen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29175445", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 317, "text": "High levels of COL6A3 and its cleaved product, endotrophin (ETP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30246318", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 192, "text": "Endotrophin is released from COL VI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29229941", "endSection": "abstract" } ] }, { "body": "Which receptor is inhibited by bimagrumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27167138", "http://www.ncbi.nlm.nih.gov/pubmed/25381300", "http://www.ncbi.nlm.nih.gov/pubmed/24298022", "http://www.ncbi.nlm.nih.gov/pubmed/29226558", "http://www.ncbi.nlm.nih.gov/pubmed/31761834", "http://www.ncbi.nlm.nih.gov/pubmed/26506009", "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "http://www.ncbi.nlm.nih.gov/pubmed/27462398", "http://www.ncbi.nlm.nih.gov/pubmed/28905498", "http://www.ncbi.nlm.nih.gov/pubmed/30095981" ], "ideal_answer": [ "Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators." ], "exact_answer": [ "activin type II receptors" ], "type": "factoid", "id": "5e44b04c48dab47f26000016", "snippets": [ { "offsetInBeginSection": 189, "offsetInEndSection": 313, "text": "Bimagrumab is a human anti-ActRII antibody which was found to increase muscle mass and function by blocking ActRII signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "BACKGROUND: Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1504, "text": "CONCLUSION: Bimagrumab alters the function of pituitary gonadotroph cells, consistent with blockade of activin on local ActRII. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "RATIONALE: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1644, "text": "CONCLUSIONS: Blocking the action of negative muscle regulators through the activin type II receptors with bimagrumab treatment safely increased skeletal muscle mass but did not improve functional capacity in patients with COPD and low muscle mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 552, "text": "This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Effects of bimagrumab, an activin receptor type II inhibitor, on pituitary neurohormonal axes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Bimagrumab (BYM338) is a novel fully human monoclonal antibody that exerts strong promyogenic effects on skeletal muscle by blocking activin type II receptors (ActRII).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27167138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "BACKGROUND\n\nBimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "RATIONALE\n\nBimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 806, "text": "CDD866 (murinized version of bimagrumab) is a neutralizing antibody against the activin receptor type II (ActRII) preventing binding of ligands such as myostatin and activin A, which are involved in cancer cachexia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27462398", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 483, "text": "We have developed a novel , human anti-ActRII antibody ( bimagrumab , or BYM338 ) to prevent binding of ligands to the receptors and thus inhibit downstream signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298022", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 544, "text": "This study aimed to explore the clinical potential of bimagrumab , a human monoclonal antibody targeting the activin type II receptor , for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors ( ActRII) , with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 905, "text": "Novel antiresorptive and anabolic therapies are emerging for osteoporosis as well as drugs for sarcopenia , cancer cachexia or muscle wasting disorders , including antibodies against myostatin or activin receptor type IIA and IIB ( e.g. bimagrumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26506009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "A global , randomized , double-blind placebo-controlled study was conducted to confirm that BYM338 ( bimagrumab) , an anti-activin type II receptor antibody , improves motor function in patients with sporadic inclusion body myositis after 52 weeks' treatment consisting of intravenous administration every 4 weeks at doses of 10 , 3 , and 1 mg/kg", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31761834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Bimagrumab ( BYM338 ) is a novel fully human monoclonal antibody that exerts strong promyogenic effects on skeletal muscle by blocking activin type II receptors ( ActRII", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27167138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Bimagrumab (BYM338) is a novel fully human monoclonal antibody that exerts strong promyogenic effects on skeletal muscle by blocking activin type II receptors (ActRII).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27167138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "BACKGROUND\nBimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 506, "text": "Bimagrumab also blocks other endogenous ActRII ligands, such as activins, which act on the neurohormonal axes, pituitary, gonads and adrenal glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "RATIONALE\nBimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 506, "text": "Bimagrumab also blocks other endogenous ActRII ligands, such as activins, which act on the neurohormonal axes, pituitary, gonads and adrenal glands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 474, "text": "We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24298022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1676, "text": "Blocking the action of negative muscle regulators through the activin type II receptors with bimagrumab treatment safely increased skeletal muscle mass but did not improve functional capacity in patients with COPD and low muscle mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 540, "text": "This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905498", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 784, "text": "CDD866 (murinized version of bimagrumab) is a neutralizing antibody against the activin receptor type II (ActRII) preventing binding of ligands such as myostatin and activin A, which are involved in cancer cachexia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27462398", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 452, "text": "We tested inhibition of activin receptors IIA and IIB (ActRII) in 14 patients with sIBM using one dose of bimagrumab (n = 11) or placebo (n = 3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25381300", "endSection": "abstract" } ] }, { "body": "Where is the yeast transpozable element Ty3 preferentially inserted?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22544262", "http://www.ncbi.nlm.nih.gov/pubmed/1963869", "http://www.ncbi.nlm.nih.gov/pubmed/1309715", "http://www.ncbi.nlm.nih.gov/pubmed/15579677", "http://www.ncbi.nlm.nih.gov/pubmed/11604517", "http://www.ncbi.nlm.nih.gov/pubmed/8389458" ], "ideal_answer": [ "Ty3 is preferentially inserted in genes encoding transfer RNA genes.", "The retrovirus-like element Ty3 of Saccharomyces cerevisiae integrates at the transcription initiation region of RNA polymerase III genes and is preferentially inserted in transfer RNA genes.", "Ty3 integrates within the region of RNA polymerase III transcription initiation. Thus, genomic insertions of Ty3 in a particular orientation are apparently specified by the target, while the actual position of the insertion relative to the tRNA-coding sequence can vary slightly.", "The retrovirus-like element Ty3 of Saccharomyces cerevisiae integrates at the transcription initiation region of RNA polymerase III", "The yeast transpozable element Ty3 is preferentially located in the promoter region of genes encoding ribosomal proteins.", "rna polymerase iii", "Ty3 inserts at transcription initiation sites of genomic tRNA genes and plasmid-borne 5S and U6 RNA genes transcribed by RNA polymerase III." ], "exact_answer": [ "the promoters of RNA PolIII-transcribed genes" ], "type": "factoid", "id": "5d3852d07bc3fee31f000014", "snippets": [ { "offsetInBeginSection": 730, "offsetInEndSection": 923, "text": "We found that extra ORFs occur in all three major lineages of plant Ty3/gypsy elements, being the most frequent in the Tat lineage where most (77\u00a0%) of identified elements contained extra ORFs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22544262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The retrovirus-like element Ty3 of Saccharomyces cerevisiae integrates at the transcription initiation region of RNA polymerase III.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15579677", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1063, "text": "Ty3 inserts at transcription initiation sites of genomic tRNA genes and plasmid-borne 5S and U6 RNA genes transcribed by RNA polymerase III. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11604517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Sites of RNA polymerase III transcription initiation and Ty3 integration at the U6 gene are positioned by the TATA box", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8389458", "endSection": "title" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1391, "text": " the U6 TATA box is essential in vivo for correct initiation but not for transcription, (ii) a TATA box does not compensate for a weak box A sequence and so cannot perform equivalently, and (iii) the TATA-binding protein, and probably components of transcription factor IIIB, are present on the target at the time of Ty3 integration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8389458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Ty3 integrates within the region of RNA polymerase III transcription initiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1309715", "endSection": "title" }, { "offsetInBeginSection": 115, "offsetInEndSection": 225, "text": "Ty3 was shown to insert upstream of tRNA, 5S, and U6 genes, all of which are transcribed by RNA polymerase III", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1309715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Transfer RNA genes are genomic targets for de Novo transposition of the yeast retrotransposon Ty3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1963869", "endSection": "title" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1342, "text": "Thus, genomic insertions of Ty3 in a particular orientation are apparently specified by the target, while the actual position of the insertion relative to the tRNA-coding sequence can vary slightly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1963869", "endSection": "abstract" } ] }, { "body": "List features of the Currarino triad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27549440", "http://www.ncbi.nlm.nih.gov/pubmed/7756242", "http://www.ncbi.nlm.nih.gov/pubmed/24571710", "http://www.ncbi.nlm.nih.gov/pubmed/26793693", "http://www.ncbi.nlm.nih.gov/pubmed/29801510", "http://www.ncbi.nlm.nih.gov/pubmed/29352751", "http://www.ncbi.nlm.nih.gov/pubmed/11528505", "http://www.ncbi.nlm.nih.gov/pubmed/17268712", "http://www.ncbi.nlm.nih.gov/pubmed/8740138", "http://www.ncbi.nlm.nih.gov/pubmed/29401559", "http://www.ncbi.nlm.nih.gov/pubmed/11147855", "http://www.ncbi.nlm.nih.gov/pubmed/12847376", "http://www.ncbi.nlm.nih.gov/pubmed/6728549", "http://www.ncbi.nlm.nih.gov/pubmed/16732824", "http://www.ncbi.nlm.nih.gov/pubmed/23015348", "http://www.ncbi.nlm.nih.gov/pubmed/29731315" ], "ideal_answer": [ "Currarino syndrome is a congenital malformation syndrome typically characterized by sacral agenesis, anorectal malformation, and presence of a pre-sacral mass." ], "exact_answer": [ [ "sacral agenesis" ], [ "anorectal malformation" ], [ "pre-sacral mass" ] ], "type": "list", "id": "5e342175fbd6abf43b000064", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "BACKGROUND: The major genetic cause of Currarino syndrome (CS), a congenital malformation syndrome typically characterized by sacral agenesis, anorectal malformation, and presence of a pre-sacral mass, is known to be pathogenic variants in motor neuron and pancreas homeobox 1 (MNX1), which exist in almost all familial cases and 30% of sporadic cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29401559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "BACKGROUND: The Currarino triad is a rare hereditary syndrome comprising anorectal malformation, sacral bony defect, and presacral mass. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29352751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "INTRODUCTION: Currarino's syndrome (CS) is an autosomal dominant disorder of embryonic development causing a rare malformating syndrome characterized by a triad of an anorectal malformations, presacral mass (most commonly an anterior sacral meningocele) and sacral bony defects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29731315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND: Currarino syndrome is a rare condition characterized by presacral mass, anorectal malformation and sacral dysgenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29801510", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 838, "text": "The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27549440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "PURPOSE\n\nCurrarino triad, which comprises anorectal stenosis, anterior sacral defect, and a presacral mass, is an uncommon cause of constipation in children and adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12847376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The Currarino triad , also known as the \" Currarino Syndrome \" , is a rare complex of congenital caudal anomalies including three main features; a sacral bony deformity , anorectal malformations , and a presacral mass", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The association of congenital anal stenosis , scimitar-shaped sacral defect and a presacral mass is known as the Currarino triad", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7756242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The triad of a presacral tumour , sacral agenesis and anorectal malformation constitutes the Currarino syndrome which is caused by dorsal-ventral patterning defects during embryonic development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11528505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Currarino syndrome ( Currarino triad ) was described in 1981 as a triad syndrome with a common embryogenesis in infants and with three characteristics: anorectal stenosis , a defect in the sacral bone , and a presacral mass", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24571710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The Currarino triad is a hereditary transmitted syndrome , originally defined by Currarino as ASP-association , consisting of an anorectal malformation , a sacral bony defect and a presacral mass", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8740138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "PURPOSE\nCurrarino triad, which comprises anorectal stenosis, anterior sacral defect, and a presacral mass, is an uncommon cause of constipation in children and adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12847376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "PURPOSE: Currarino triad, which comprises anorectal stenosis, anterior sacral defect, and a presacral mass, is an uncommon cause of constipation in children and adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12847376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The Currarino triad: complex of anorectal malformation, sacral bony abnormality, and presacral mass.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6728549", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The Currarino triad is a unique complex of congenital caudal anomalies including anorectal malformation, sacral bony abnormality, and presacral mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6728549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16732824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Currarino triad is a rare congenital condition characterized by a sacral bony defect, presacral mass, and anorectal malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17268712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The Currarino triad is a unique complex of congenital caudal anomalies, including anorectal malformation, sacral bony defect and presacral mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26793693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The Currarino triad is a unique complex of congenital caudal anomalies including anorectal malformation, sacral bone abnormality, and presacral mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11147855", "endSection": "abstract" } ] }, { "body": "When was Afrezza approved by the FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26222134" ], "ideal_answer": [ "Afrezza was approved by the FDA in June 2014." ], "exact_answer": [ "June 2014" ], "type": "factoid", "id": "5e776cfe835f4e4777000010", "snippets": [ { "offsetInBeginSection": 635, "offsetInEndSection": 908, "text": "In contrary, MannKind Corporation started developing its ultra-rapid-acting insulin Afrezza in a bold bid, probably by managing the issues in which Exubera was not successful. Afrezza has been marketed since February, 2015 by Sanofi after getting FDA approval in June 2014.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222134", "endSection": "abstract" } ] }, { "body": "What are invasomes", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21745556", "http://www.ncbi.nlm.nih.gov/pubmed/26002568", "http://www.ncbi.nlm.nih.gov/pubmed/18316200", "http://www.ncbi.nlm.nih.gov/pubmed/29318969" ], "ideal_answer": [ "Ultra-flexible vesicles, e.g. invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems", "invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems for dermatological applications.", "Invasomes are novel vesicular systems that exhibit improved transdermal penetration compared to conventional liposomes." ], "type": "summary", "id": "5e6ea5b9c6a8763d23000008", "snippets": [ { "offsetInBeginSection": 212, "offsetInEndSection": 331, "text": "Ultra-flexible vesicles, e.g. invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745556", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1137, "text": " Invasomes are vesicles containing in addition to phospholipids a mixture of terpenes (cineole, citral and d-limonene) or only one terpene (citral) and ethanol, as penetration enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18316200", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 363, "text": "invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems for dermatological applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745556", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 364, "text": "invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems for dermatological applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21745556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The present study compares three vesicular systems, cationic LeciPlex, invasomes, and conventional liposomes for their ability to deliver drugs deep into the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26002568", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 919, "text": "The present write up elaborates the mechanism of penetration, and compiles literature dental applications of the invasomes, the detection ability, use in photodynamic therapy, pilosebaceous targeting, and for delivery of macromolecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29318969", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 565, "text": "The present review focuses on the update of the research activity on effectiveness and permeation enhancing effects of invasomes for dermal and topical delivery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29318969", "endSection": "abstract" } ] }, { "body": "Which T-UCRs have been implicated in lung cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29180617", "http://www.ncbi.nlm.nih.gov/pubmed/30195756" ], "ideal_answer": [ "Transcribed ultraconserved regions (T-UCRs) classified as long non-coding RNAs (Lnc-RNAs) are transcripts longer than 200-nt RNA with no protein-coding capacity. The clinicopathologic significance and regulatory mechanism of T-UCRs in lung cancer (LC) remain largely unknown. Uc.454 is downregulated in both non-small-cell LC (NSCLC) tissues and LC cell lines, and the downregulated uc.454 is associated with tumor size and tumors with more advanced stages. Transfection with uc.454 markedly induces apoptosis and inhibites cell proliferation in SPC-A-1 and NCI-H2170 LC cell lines. Thus uc.454 potentially plays a suppressive role in LC. Transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels." ], "exact_answer": [ [ "uc.454" ], [ "uc.339" ] ], "type": "list", "id": "5e36a901b5b409ea53000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in Non-Small-Cell Lung Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30195756", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1246, "text": "Transcribed ultraconserved regions (T-UCRs) classified as long non-coding RNAs (Lnc-RNAs) are transcripts longer than 200-nt RNA with no protein-coding capacity. Previous studies showed that T-UCRs serve as novel oncogenes, or tumor suppressors are involved in tumorigenesis and cancer progressive. Nevertheless, the clinicopathologic significance and regulatory mechanism of T-UCRs in lung cancer (LC) remain largely unknown. We found that uc.454 was downregulated in both non-small-cell LC (NSCLC) tissues and LC\u00a0cell lines, and the downregulated uc.454 is associated with tumor size and tumors with more advanced stages. Transfection with uc.454 markedly induced apoptosis and\u00a0inhibited cell proliferation in SPC-A-1 and NCI-H2170 LC cell lines. Above results suggested that uc.454 played a suppressive role in LC. Heat shock protein family\u00a0A member 12B (HSPA12B) protein was negatively regulated by uc.454 at the posttranscriptional level by dual-luciferase reporter assay and affected the expressions of Bcl-2 family members, which finally induced LC apoptosis. The uc.454/HSPA12B axis furthers our understanding of the molecular mechanisms involved in tumor apoptosis, which may potentially serve as a therapeutic target for lung carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30195756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29180617", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1006, "text": "The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no\u00a0significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call \"entrapping\". Our results support a key role for uc.339 in lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29180617", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1006, "text": "Our results support a key role for uc.339 in lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29180617", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 343, "text": "Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29180617", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1246, "text": "The uc.454/HSPA12B axis furthers our understanding of the molecular mechanisms involved in tumor apoptosis, which may potentially serve as a therapeutic target for lung carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30195756", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 817, "text": "Above results suggested that uc.454 played a suppressive role in LC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30195756", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1247, "text": "The uc.454/HSPA12B axis furthers our understanding of the molecular mechanisms involved in tumor apoptosis, which may potentially serve as a therapeutic target for lung carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30195756", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 624, "text": "We found that uc.454 was downregulated in both non-small-cell LC (NSCLC) tissues and LC\u00a0cell lines, and the downregulated uc.454 is associated with tumor size and tumors with more advanced stages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30195756", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 749, "text": "Transfection with uc.454 markedly induced apoptosis and\u00a0inhibited cell proliferation in SPC-A-1 and NCI-H2170 LC cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30195756", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1007, "text": "Our results support a key role for uc.339 in lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29180617", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 344, "text": "Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29180617", "endSection": "abstract" } ] }, { "body": "Can Daptacel be used instead of IPOL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19117896" ], "ideal_answer": [ "No, Daptacel is a diphtheria, tetanus, 5-component acellular pertussis vaccine, while IPOL is an inactivated poliovirus vaccine." ], "exact_answer": "no", "type": "yesno", "id": "5e7f6090835f4e477700001a", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 582, "text": "Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP(5) dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117896", "endSection": "abstract" }, { "offsetInBeginSection": 2153, "offsetInEndSection": 2251, "text": "DTaP(5)-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117896", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 825, "text": " In this randomized, multicenter study, 1939 healthy infants were immunized at 2, 4, and 6 months of age with 1 of 3 lots of DTaP(5) coadministered with IPV and Hib vaccines or 1 lot of DTaP(5)-IPV-Hib combination vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117896", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1284, "text": "DTaP(5)-IPV-Hib elicited similar or fewer solicited injection-site and systemic reactions as compared with the separate administration of US-licensed DTaP(5), IPV, and Hib vaccines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117896", "endSection": "abstract" } ] }, { "body": "Is ACE2 expressed on cell surfaces?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27889958", "http://www.ncbi.nlm.nih.gov/pubmed/28116710" ], "ideal_answer": [ "Yes,\nACE2 is a type 1 integral membrane protein and contains a catalytically active ectodomain that can be shed from the cell surface into the extracellular space." ], "exact_answer": "yes", "type": "yesno", "id": "5e806ff7835f4e4777000027", "snippets": [ { "offsetInBeginSection": 729, "offsetInEndSection": 836, "text": " Recent studies reported that shedding of the enzymatically active ectodomain of ACE2 from the cell surface", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27889958", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 378, "text": "ACE2 is a type 1 integral membrane protein and contains a catalytically active ectodomain that can be shed from the cell surface into the extracellular space,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28116710", "endSection": "abstract" } ] }, { "body": "List symptoms of the One-and-a-half syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18410825", "http://www.ncbi.nlm.nih.gov/pubmed/18198796", "http://www.ncbi.nlm.nih.gov/pubmed/24424330", "http://www.ncbi.nlm.nih.gov/pubmed/31764815", "http://www.ncbi.nlm.nih.gov/pubmed/28905844", "http://www.ncbi.nlm.nih.gov/pubmed/23434442", "http://www.ncbi.nlm.nih.gov/pubmed/11725188", "http://www.ncbi.nlm.nih.gov/pubmed/24674953", "http://www.ncbi.nlm.nih.gov/pubmed/25911021", "http://www.ncbi.nlm.nih.gov/pubmed/10525768", "http://www.ncbi.nlm.nih.gov/pubmed/28347678", "http://www.ncbi.nlm.nih.gov/pubmed/29312874", "http://www.ncbi.nlm.nih.gov/pubmed/23914112", "http://www.ncbi.nlm.nih.gov/pubmed/21917272" ], "ideal_answer": [ "One-and-a-half syndrome is defined by conjugated horizontal gaze palsy and internuclear ophthalmoplegia." ], "exact_answer": [ [ "conjugated horizontal gaze palsy" ], [ "internuclear ophthalmoplegia" ] ], "type": "list", "id": "5e3a6a4eb5b409ea53000016", "snippets": [ { "offsetInBeginSection": 316, "offsetInEndSection": 530, "text": "She experienced diplopia on right horizontal gaze due to a left internuclear ophthalmoplegia (INO) with an associated left conjugate horizontal gaze palsy, collectively described as a left one-and-a-half syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28347678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "We report a case of 43-year-old male, presented with sudden onset binocular diplopia on lateral gazes. Ocular examination showed features of ipsilateral one-and-a-half syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "One-and-a-half syndrome is a syndrome characterized by horizontal movement disorders of the eyeballs, which was first reported and named by Fisher in 1967. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29312874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND AND PURPOSE: Unilateral gaze palsy associated with internuclear ophthalmoplegia (INO), i.e., one-and-a-half syndrome, is well known. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25911021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "We describe a rare case in which both wall-eyed bilateral internuclear ophthalmoplegia syndrome and vertical one-and-a-half syndrome were observed in a 68-year-old man with acute ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24424330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "\"Eight-and-a-half\" syndrome is \"one-and-a-half\" syndrome (conjugated horizontal gaze palsy and internuclear ophthalmoplegia) plus ipsilateral fascicular cranial nerve seventh palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24674953", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 408, "text": "On examination, she had left fascicular type of third nerve palsy, vertical one and half syndrome (VOHS), left internuclear ophthalmoplegia and skew deviation with ipsilesional hypertropia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23914112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "\"Eight-and-a-half\" syndrome is \"one-and-a-half\" syndrome (conjugated horizontal gaze palsy and internuclear ophthalmoplegia) plus ipsilateral fascicular cranial nerve seventh palsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23434442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "We report a unique neuroophthalmological syndrome consisting of vertical one-and-a-half syndrome-resulting from a combination of supranuclear conjugate upgaze palsy associated with left infranuclear (fascicular) third nerve involvement (Weber syndrome)-with concomitant contralesional pseudo-abducens palsy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21917272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "One-and-a-half syndrome is a clinical disorder featuring extraocular movements characterized by horizontal conjugate gaze palsy with internuclear ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The one-and-a-half syndrome is characterised by a lateral gaze palsy in one direction and internuclear ophthalmoplegia in the other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10525768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "RATIONALE One-and-a-half syndrome (OAAH) is characterized as the combination of ipsilateral horizontal gaze palsy and internuclear ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31764815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "RATIONALE\n\nOne-and-a-half syndrome (OAAH) is characterized as the combination of ipsilateral horizontal gaze palsy and internuclear ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31764815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "One-and-a-half syndrome is characterized by combination of the clinical features of unilateral horizontal gaze palsy and internuclear ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18198796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The one-and-a-half syndrome is characterised by a lateral gaze palsy in one direction and internuclear ophthalmoplegia in the other . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10525768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "One-and-a-half syndrome is a clinical disorder featuring extraocular movements characterized by horizontal conjugate gaze palsy with internuclear ophthalmoplegia . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "One-and-a-half syndrome is characterized by combination of the clinical features of unilateral horizontal gaze palsy and internuclear ophthalmoplegia . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18198796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "A 52-year-old patient developed an eye movement disorder first resembling a left internuclear ophthalmoplegia and subsequently a \" one-and-a-half syndrome \" as the presenting symptoms of ocular myasthenia gravis . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11725188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The one-and-a-half syndrome is characterised by a lateral gaze palsy in one direction and internuclear ophthalmoplegia in the other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10525768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "RATIONALE\nOne-and-a-half syndrome (OAAH) is characterized as the combination of ipsilateral horizontal gaze palsy and internuclear ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31764815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "One-and-a-half syndrome (OAAH) is characterized as the combination of ipsilateral horizontal gaze palsy and internuclear ophthalmoplegia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31764815", "endSection": "abstract" } ] }, { "body": "When was Fluzone Intradermal replaced with Fluzone Intradermal Quadrivalent?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27457797" ], "ideal_answer": [ "Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine in advance of the 2015-2016 season." ], "exact_answer": [ "In advance of the 2015-2016 season" ], "type": "factoid", "id": "5e7f5d0d835f4e4777000016", "snippets": [ { "offsetInBeginSection": 322, "offsetInEndSection": 569, "text": "In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9\u00a0\u00b5g hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27457797", "endSection": "abstract" } ] }, { "body": "List the cancers that are associated with SBLA syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3632013", "http://www.ncbi.nlm.nih.gov/pubmed/2300390", "http://www.ncbi.nlm.nih.gov/pubmed/2249207", "http://www.ncbi.nlm.nih.gov/pubmed/10640978", "http://www.ncbi.nlm.nih.gov/pubmed/24107814", "http://www.ncbi.nlm.nih.gov/pubmed/8197773", "http://www.ncbi.nlm.nih.gov/pubmed/2827818" ], "ideal_answer": [ "Li-Fraumeni syndrome is an autosomal dominant inherited disorder also known as the SBLA cancer syndrome (sarcoma, breast, leukemia, and adrenal). Li-Fraumeni syndrome (LFS) is characterized by a pleth", "SBLA cancer syndrome (sarcoma, breast, leukemia, and adrenal).", "Li-Fraumeni syndrome is an autosomal dominant inherited disorder also known as the SBLA cancer syndrome (sarcoma, breast, brain, lung, lymphoma, leukemia, laryngeal and adrenal)." ], "exact_answer": [ [ "sarcoma" ], [ "breast cancer" ], [ "leukemia" ], [ "adrenal" ], [ "lung" ], [ "lymphoma," ], [ "brain" ], [ "laryngeal" ] ], "type": "list", "id": "5e639b111af46fc130000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Li-Fraumeni syndrome is an autosomal dominant inherited disorder also known as the SBLA cancer syndrome (sarcoma, breast, leukemia, and adrenal).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107814", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 232, "text": "Li-Fraumeni syndrome (LFS) is characterized by a plethora of cancers, most prominent of which is carcinoma of the breast followed by sarcomas, brain tumors, leukemia, lymphoma, lung carcinoma, and adrenocortical carcinom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10640978", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 244, "text": "sarcoma, breast cancer and brain tumors, lung and laryngeal cancer, leukemia, lymphoma, and adrenalcortical carcinoma syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2300390", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 647, "text": "sarcomas, brain tumors, leukemia, lymphoma, and adrenal cortical carcinoma ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8197773", "endSection": "abstract" }, { "offsetInBeginSection": 1374, "offsetInEndSection": 1571, "text": "The SBLA syndrome is a complex familial cancer syndrome characterized by a proclivity to Sarcomas, Breast cancers, brain tumors, Lung and laryngeal cancers, leukemia, and Adrenocortical carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2827818", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 703, "text": "In addition to HBOC, one sees a variety of putative breast cancer-prone genotypes inclusive of hereditary site-specific breast cancer, and the Li-Fraumeni (SBLA) syndrome that is characterized by cancers involving all three germinal layers including sarcomas, brain tumors, leukemia, lymphoma, and adrenal cortical carcinoma in addition to often markedly early-onset breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8197773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "BACKGROUND\n\nLi-Fraumeni syndrome (LFS) is characterized by a plethora of cancers, most prominent of which is carcinoma of the breast followed by sarcomas, brain tumors, leukemia, lymphoma, lung carcinoma, and adrenocortical carcinoma (therefore, also referred to by the acronym SBLA syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10640978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Li-Fraumeni syndrome is an autosomal dominant inherited disorder also known as the SBLA cancer syndrome ( sarcoma , breast , leukemia , and adrenal) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107814", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 400, "text": "A carcinoma of the choroid plexus occurred in a child from a family with the breast cancer-sarcoma syndrome ( Li-Fraumeni or SBLA syndrome) , an inherited condition characterized by the development of diverse neoplasms ( sarcoma , breast cancer , brain tumors , leukemia , adrenal cortical carcinoma , and others) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2249207", "endSection": "abstract" }, { "offsetInBeginSection": 1396, "offsetInEndSection": 1599, "text": "The SBLA syndrome is a complex familial cancer syndrome characterized by a proclivity to Sarcomas , Breast cancers , brain tumors , Lung and laryngeal cancers , leukemia , and Adrenocortical carcinomas .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2827818", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 775, "text": "Evidence from extended pedigrees , however , indicates that at least four of the children could be members of families with the SBLA ( sarcoma , breast and brain tumour , leukaemia , laryngeal and lung cancer , and adrenal cortical carcinoma ) cancer family syndrome , and that other relatives may be at risk of developing such neoplasms .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3632013", "endSection": "abstract" }, { "offsetInBeginSection": 1374, "offsetInEndSection": 1572, "text": "The SBLA syndrome is a complex familial cancer syndrome characterized by a proclivity to Sarcomas, Breast cancers, brain tumors, Lung and laryngeal cancers, leukemia, and Adrenocortical carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2827818", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 704, "text": "In addition to HBOC, one sees a variety of putative breast cancer-prone genotypes inclusive of hereditary site-specific breast cancer, and the Li-Fraumeni (SBLA) syndrome that is characterized by cancers involving all three germinal layers including sarcomas, brain tumors, leukemia, lymphoma, and adrenal cortical carcinoma in addition to often markedly early-onset breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8197773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Li-Fraumeni syndrome (LFS) is characterized by a plethora of cancers, most prominent of which is carcinoma of the breast followed by sarcomas, brain tumors, leukemia, lymphoma, lung carcinoma, and adrenocortical carcinoma (therefore, also referred to by the acronym SBLA syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10640978", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 757, "text": "Evidence from extended pedigrees, however, indicates that at least four of the children could be members of families with the SBLA (sarcoma, breast and brain tumour, leukaemia, laryngeal and lung cancer, and adrenal cortical carcinoma) cancer family syndrome, and that other relatives may be at risk of developing such neoplasms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3632013", "endSection": "abstract" } ] }, { "body": "Can leuprorelin acetate be used as androgen deprivation therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29183006" ], "ideal_answer": [ "Yes, leuprorelin acetate is being used as androgen deprivation therapy." ], "exact_answer": "yes", "type": "yesno", "id": "5e7744c3835f4e4777000005", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 206, "text": "We investigated the health-related quality of life (HRQoL) of long-term prostate cancer patients who received leuprorelin acetate in microcapsules (LAM) for androgen-deprivation therapy (ADT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29183006", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1576, "text": "Long-term ADT with LAM is a well-accepted, tolerated, effective, and low-burden treatment option for patients with advanced, hormone-sensitive PCa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29183006", "endSection": "abstract" } ] }, { "body": "Which factors are included in the the APPEND score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28512853" ], "ideal_answer": [ "APPEND score components are anorexia, migratory Pain, local Peritonism, Elevated C-reactive protein, Neutrophilia and male gender (Dude). It is an acute appendicitis clinical prediction rule." ], "exact_answer": [ [ "anorexia" ], [ "migratory Pain" ], [ "local Peritonism" ], [ "Elevated C-reactive protein" ], [ "Neutrophilia" ], [ "male gender" ] ], "type": "list", "id": "5e475d3035b8f0833c000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Derivation and validation of the APPEND score: an acute appendicitis clinical prediction rule.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28512853", "endSection": "title" }, { "offsetInBeginSection": 775, "offsetInEndSection": 954, "text": "RESULTS: The final components of the new CPR, the APPEND score, were Anorexia, migratory Pain, local Peritonism, Elevated C-reactive protein, Neutrophilia and male gender (Dude). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28512853", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 957, "text": "RESULTS\nThe final components of the new CPR, the APPEND score, were Anorexia, migratory Pain, local Peritonism, Elevated C-reactive protein, Neutrophilia and male gender (Dude).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28512853", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 953, "text": "RESULTS: The final components of the new CPR, the APPEND score, were Anorexia, migratory Pain, local Peritonism, Elevated C-reactive protein, Neutrophilia and male gender (Dude).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28512853", "endSection": "abstract" } ] }, { "body": "What is the function of the SSX proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17667940", "http://www.ncbi.nlm.nih.gov/pubmed/10072425", "http://www.ncbi.nlm.nih.gov/pubmed/10739666", "http://www.ncbi.nlm.nih.gov/pubmed/20981248", "http://www.ncbi.nlm.nih.gov/pubmed/21880588", "http://www.ncbi.nlm.nih.gov/pubmed/17018603" ], "ideal_answer": [ "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors", "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Together, we conclude that the SS18-SSX2 fusion protein may act as a so-called transcriptional \"activator-repressor,\" which induces downstream target gene deregulation through epigenetic mechanisms. The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (de)regulation. Taken together, these results led us to conclude that the SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus.", "transcriptional co-activator", "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors Taken together, these results led us to conclude that the SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus.", "The SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus.", "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Taken together, these results led us to conclude that the SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus. The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (de)regulation." ], "type": "summary", "id": "5d386d66a1e1595105000003", "snippets": [ { "offsetInBeginSection": 190, "offsetInEndSection": 292, "text": "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10072425", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1341, "text": "Taken together, these results led us to conclude that the SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10739666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (de)regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17018603", "endSection": "title" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1607, "text": "Together, we conclude that the SS18-SSX2 fusion protein may act as a so-called transcriptional \"activator-repressor,\" which induces downstream target gene deregulation through epigenetic mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17018603", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1757, "text": "Taken together, we conclude that this novel protein - protein interaction may have direct consequences for the (de)regulation of SSX and/or SS18-SSX target genes and, thus, for the development of human synovial sarcomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17667940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The SSX family of cancer-testis antigens as target proteins for tumor therapy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981248", "endSection": "title" }, { "offsetInBeginSection": 625, "offsetInEndSection": 786, "text": "Of particular interest among CTAs is the synovial sarcoma X chromosome breakpoint (SSX) family of proteins, which includes ten highly homologous family members. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981248", "endSection": "abstract" }, { "offsetInBeginSection": 1500, "offsetInEndSection": 1644, "text": "Our findings suggest that multiple SSX family members are expressed in metastatic prostate cancers which are amenable to simultaneous targeting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21880588", "endSection": "abstract" } ] }, { "body": "Are astrocytes part of the blood brain barrier?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28883042", "http://www.ncbi.nlm.nih.gov/pubmed/28822114" ], "ideal_answer": [ "Yes\nThe blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation." ], "exact_answer": "yes", "type": "yesno", "id": "5e6e35b07fc1ee872b000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28822114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28883042", "endSection": "abstract" } ] }, { "body": "What is Invaplex 50?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20619378" ], "ideal_answer": [ "The Shigella flexneri Invaplex 50 is a macromolecular complex containing IpaB, IpaC, and LPS, formulated from an aqueous extract of virulent Shigella delivered via nasal administration. It is used against shigellosis, a leading cause of diarrhea worldwide. The Invaplex 50 nasal vaccine was safe with encouraging mucosal immune responses." ], "type": "summary", "id": "5e776c98835f4e477700000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Safety and immunogenicity of a Shigella flexneri 2a Invaplex 50 intranasal vaccine in adult volunteers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20619378", "endSection": "title" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1077, "text": " The Invaplex 50 nasal vaccine was safe with encouraging mucosal immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20619378", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 669, "text": "The vaccine was well tolerated with minor short-lived nasal symptoms without evidence of dose effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20619378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Shigellosis is a leading cause of diarrhea worldwide prompting vaccine development. The Shigella flexneri Invaplex 50 is a macromolecular complex containing IpaB, IpaC, and LPS, formulated from an aqueous extract of virulent Shigella delivered via nasal administration. Preclinical vaccine testing demonstrated safety, immunogenicity and efficacy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20619378", "endSection": "abstract" } ] }, { "body": "Which X chromosome abnormalities present lupus-like symptoms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18606711" ], "ideal_answer": [ "Lupus-like symptoms of systemic lupus erythematosus (SLE) are caused by X-linked mutations in the genes Tlr7 and Y.", "Yaa-mediated acceleration of SLE as well as various Yaa-linked cellular traits cannot be explained by the Tlr7 gene duplication alone, and suggest additional contributions from other duplicated genes in the translocated X chromosome.", "genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration).", "Tlr7 and Y chromosome abnormalities present lupus-like symptoms with considerable phenotypic overlap.", "X-chromosome abnormalities (Tlr7 and Y) present lupus-like symptoms.", "the accelerated development of systemic lupus erythematosus (sle) in male bxsb mice is associated with the genetic abnormality in its y chromosome", "Yaa-mediated acceleration of SLE as well as various Yaa-linked cellular traits cannot be explained by the Tlr7 gene duplication alone, and suggest additional contributions from other duplicated genes in the translocated X chromosome. The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration).", "The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration) but additional contributions from other duplicated genes in the translocated X chromosome also exist", "The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration).", "X-chromosomal abnormalities in patients with SLE present lupus-like symptoms. X-chromatin abnormality on X chromosome 14q11.2, which encodes X-linked leiomyosarcoma, is the most common chromosomal abnormality in SLE. There is also a publication that links X- chromosome abnormalities to lupUS disease with synostosis.", "The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration). Yaa-mediated acceleration of SLE as well as various Yaa-linked cellular traits cannot be explained by the Tlr7 gene duplication alone, and suggest additional contributions from other duplicated genes in the translocated X chromosome.", "yaa", "Lupus-like symptoms are present due to X-chromosomal abnormalities such as X-linked leiomyosarcoma, polycystic kidney disease, myelodysplastic syndrome (MDS), and X- linked hypogonadotropic hypomyelitis." ], "exact_answer": [ [ "Y-linked autoimmune acceleration", "Yaa" ], [ "X-linked translocations" ] ], "type": "list", "id": "5d38790da1e159510500000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606711", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1573, "text": "Yaa-mediated acceleration of SLE as well as various Yaa-linked cellular traits cannot be explained by the Tlr7 gene duplication alone, and suggest additional contributions from other duplicated genes in the translocated X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606711", "endSection": "abstract" } ] }, { "body": "Which lncRNAS are regulated by SAM68?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29137239" ], "ideal_answer": [ "Hotair, Mir155hg, as well as SR-lncRNA-1 and SR-lncRNA-2 are regulated by Sam68, and contained consensus Sam68 binding sites." ], "exact_answer": [ [ "Hotair" ], [ "Mir155hg" ], [ "SR-lncRNA-1" ], [ "SR-lncRNA-2" ] ], "type": "list", "id": "5e493a3e6d0a277941000002", "snippets": [ { "offsetInBeginSection": 451, "offsetInEndSection": 1394, "text": "As expected, downregulated genes were significantly associated with GO terms linked to cell migration, motility, and fat cell differentiation, while upregulated genes were mostly associated with GO terms linked to neurogenesis. Of the lncRNAs, we identified Hotair, Mir155hg, as well as two new lncRNAs (SR-lncRNA-1 and SR-lncRNA-2) that were regulated by Sam68, and contained consensus Sam68 binding sites. RNA stability assays showed that Sam68-deficiency decreased the half-life of Hotair, and increased the half-lives of Mir155hg and SR-lncRNA-2, while the stability of SR-lncRNA-1 was unaffected. Depletion of Hotair and SR-lncRNA-1 in wild type 3T3-L1 cells led to defects in adipogenesis, whereas depletion of SR-lncRNA-2 in Sam68-deficient 3T3-L1 cells partially rescued the adipogenesis defect observed in these cells. Collectively, our findings define a new role for Sam68 as a regulator of lncRNAs during adipogenic differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137239", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 862, "text": "Of the lncRNAs, we identified Hotair , Mir155hg , as well as two new lncRNAs ( SR-lncRNA-1 and SR-lncRNA-2 ) that were regulated by Sam68, and contained consensus Sam68 binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137239", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 859, "text": "Of the lncRNAs, we identified Hotair, Mir155hg, as well as two new lncRNAs (SR-lncRNA-1 and SR-lncRNA-2) that were regulated by Sam68, and contained consensus Sam68 binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137239", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 858, "text": "Of the lncRNAs, we identified Hotair, Mir155hg, as well as two new lncRNAs (SR-lncRNA-1 and SR-lncRNA-2) that were regulated by Sam68, and contained consensus Sam68 binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137239", "endSection": "abstract" } ] }, { "body": "How many proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23222005" ], "ideal_answer": [ "Over 5,000 proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM).", "5,000 proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM).", "Defining protein-protein interactions in protein complexes, and establishing the when, what and where of potential interactions, is crucial to understanding the cellular function of any protein-especially those that have not been well studied by traditional molecular genetic approaches. In the Drosophila protein interaction map (DPiM) protein partners of nearly 5,000 Drosophila melanogaster proteins have been identified." ], "exact_answer": [ "5,000" ], "type": "factoid", "id": "5e35dc26158f994d3a000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1320, "text": "Proteins perform essential cellular functions as part of protein complexes, often in conjunction with RNA, DNA, metabolites and other small molecules. The genome encodes thousands of proteins but not all of them are expressed in every cell type; and expressed proteins are not active at all times. Such diversity of protein expression and function accounts for the level of biological intricacy seen in nature. Defining protein-protein interactions in protein complexes, and establishing the when, what and where of potential interactions, is therefore crucial to understanding the cellular function of any protein-especially those that have not been well studied by traditional molecular genetic approaches. We generated a large-scale resource of affinity-tagged expression-ready clones and used co-affinity purification combined with tandem mass-spectrometry to identify protein partners of nearly 5,000 Drosophila melanogaster proteins. The resulting protein complex \"map\" provided a blueprint of metazoan protein complex organization. Here we describe how the map has provided valuable insights into protein function in addition to generating hundreds of testable hypotheses. We also discuss recent technological advancements that will be critical in addressing the next generation of questions arising from the map.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23222005", "endSection": "abstract" } ] }, { "body": "What is known about the orphan receptor GPR151?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30373770", "http://www.ncbi.nlm.nih.gov/pubmed/27913310", "http://www.ncbi.nlm.nih.gov/pubmed/29691411", "http://www.ncbi.nlm.nih.gov/pubmed/28657115", "http://www.ncbi.nlm.nih.gov/pubmed/25116430" ], "ideal_answer": [ "Gpr151 is an orphan GPCR whose function is unknown. The restricted pattern of neuronal expression in the habenula, dorsal horn of the spinal cord and dorsal root ganglion plus homology with the galanin family of receptors imply a role in nociception. \nOur data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development." ], "type": "summary", "id": "5e6de9441af46fc130000023", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 261, "text": " Gpr151 is an orphan GPCR whose function is unknown. The restricted pattern of neuronal expression in the habenula, dorsal horn of the spinal cord and dorsal root ganglion plus homology with the galanin family of receptors imply a role in nociception", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27913310", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 697, "text": " pLOF variants in the gene GPR151 protect against obesity and type 2 diabetes, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "G-protein-coupled receptors are considered to be cell-surface sensors of extracellular signals, thereby having a crucial role in signal transduction and being the most fruitful targets for drug discovery. G-protein-coupled receptor 151 (GPR151) was reported to be expressed specifically in the habenular area.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30373770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116430", "endSection": "title" }, { "offsetInBeginSection": 456, "offsetInEndSection": 715, "text": "Here we investigated the expression pattern of GPR151, a G protein-coupled receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and translating ribosome affinity purification (TRAP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116430", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1588, "text": "Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "GPR151 is a G-protein coupled receptor for which the endogenous ligand remains unknown. In the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657115", "endSection": "abstract" } ] }, { "body": "Is Li\u2013Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19086841", "http://www.ncbi.nlm.nih.gov/pubmed/22551548", "http://www.ncbi.nlm.nih.gov/pubmed/29985349", "http://www.ncbi.nlm.nih.gov/pubmed/28818333", "http://www.ncbi.nlm.nih.gov/pubmed/25945745", "http://www.ncbi.nlm.nih.gov/pubmed/30004834", "http://www.ncbi.nlm.nih.gov/pubmed/31719101", "http://www.ncbi.nlm.nih.gov/pubmed/28218344", "http://www.ncbi.nlm.nih.gov/pubmed/30588330", "http://www.ncbi.nlm.nih.gov/pubmed/29946497", "http://www.ncbi.nlm.nih.gov/pubmed/27516001", "http://www.ncbi.nlm.nih.gov/pubmed/20213384", "http://www.ncbi.nlm.nih.gov/pubmed/10484981" ], "ideal_answer": [ "Li-Fraumeni syndrome is a rare, autosomal DOMINANT, hereditary disorder that predisposes carriers to cancer development.", "Yes, Li-Fraumeni syndrome is a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development.", "li-fraumeni syndrome is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion" ], "exact_answer": "no", "type": "yesno", "id": "5e639a8b1af46fc130000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion that involves a germline mutation of tumor protein 53 (TP53). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29946497", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 434, "text": "Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition caused by germline TP53 mutations, confers significant cancer risks for young people (15-39 years). Yet evidence of how individuals experience this condition and the psychosocial implications are lacking. Therefore, this systematic review assessed the psychosocial implications of living with, or at risk of, an autosomal dominant condition as a young person, to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30004834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder caused by a mutation in the p53 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28218344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder occurring at a young age that predisposes individuals to multiple forms of cancer and to a heterogeneous spectrum of malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27516001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28818333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29985349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25945745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Li-Fraumeni syndrome is a rare autosomal dominant cancer predisposition syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19086841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Li-Fraumeni syndrome is an autosomal dominant disorder that is characterized by various types of cancer in childhood and adult cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10484981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31719101", "endSection": "abstract" }, { "offsetInBeginSection": 1726, "offsetInEndSection": 1903, "text": "The Li-Fraumeni syndrome is an autosomal dominant disorder characterized by a high risk of developing osteosarcoma and has been found in up to 3% of children with osteosarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20213384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25945745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30588330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder associated with different tumor types in childhood and young adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22551548", "endSection": "abstract" } ] }, { "body": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25543845", "http://www.ncbi.nlm.nih.gov/pubmed/27587201", "http://www.ncbi.nlm.nih.gov/pubmed/23568179", "http://www.ncbi.nlm.nih.gov/pubmed/23251765", "http://www.ncbi.nlm.nih.gov/pubmed/23553779", "http://www.ncbi.nlm.nih.gov/pubmed/21081710", "http://www.ncbi.nlm.nih.gov/pubmed/29572471" ], "ideal_answer": [ "Belimumab is a fully human monoclonal antibody directed against BAFF. Belimumab, a human monoclonal antibody specific for soluble BLyS, was ultimately approved by the United States Food and Drug Administration (FDA) in March 2011 for active autoantibody patients with systemic lupus erythematosus (SLE) despite standard therapy.", "blys", "The main therapeutic target of belimumab is BLyS", "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an inv", "Belimumab is an anti-BAFF monoclonal antibody. BAFF is also known as BLyS (B-lymphocyte stimulator).", "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an investigational B-lymphocyte stimulator (BLyS) inhibitor.", "Belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (BLyS), a B-cell survival factor, was licensed in 2011 for the treatment of autoantibody-positive SLE", "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus Belimumab, an anti-BAFF monoclonal antibody", "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus Belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (BLyS), a B-cell survival factor, was licensed in 2011 for the treatment of autoantibody-positive SLE", "belimumab is a blys-specificsor for systemic lupus erythematos", "Belimumab is a fully human anti-BLyS monoclonal antibody with specificity for BLyS. It is approved for SLE treatment.", "Belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (BLyS), was licensed in 2011 for the treatment of autoantibodies to Systemic Lupus Erythematosus.", "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus.", "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an investigational B-lymphocyte stimulator (BLyS) inhibitor. Belimumab, an anti-BAFF monoclonal antibody" ], "exact_answer": [ "B-cell activating factor", "BAFF", "BLyS (B-lymphocyte stimulator)" ], "type": "factoid", "id": "5d386fbfa1e1595105000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081710", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 195, "text": "To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an investigational B-lymphocyte stimulator (BLyS) inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21081710", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 144, "text": "Belimumab, an anti-BAFF monoclonal antibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29572471", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 728, "text": "Here our crystal structure of the BAFF-belimumab Fab complex shows the precise epitope and the BAFF-neutralizing mechanism of belimumab, and demonstrates that the therapeutic activity of belimumab involves not only antagonizing the BAFF-receptor interaction, but also disrupting the formation of the more active BAFF 60-mer to favor the induction of the less active BAFF trimer through interaction with the flap region of BAFF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29572471", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1123, "text": "In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27587201", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 323, "text": "Belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (BLyS), a B-cell survival factor, was licensed in 2011 for the treatment of autoantibody-positive SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25543845", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 595, "text": "Belimumab is a fully human monoclonal antibody directed against BAFF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23568179", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 574, "text": " Belimumab, a human monoclonal antibody specific for soluble BLyS, was ultimately approved by the United States Food and Drug Administration (FDA) in March 2011 for active autoantibody patients with systemic lupus erythematosus (SLE) despite standard therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23553779", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 576, "text": "Targeted therapy with belimumab, the monoclonal antibody against BLyS, has shown clinical benefit in two large-scale, multicenter phase III trials leading to US Food and Drug Administration approval for patients with serologically positive SLE who have active disease despite standard therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23251765", "endSection": "abstract" } ] }, { "body": "Salzburg EEG criteria are used to diagnose which disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "http://www.ncbi.nlm.nih.gov/pubmed/26092326", "http://www.ncbi.nlm.nih.gov/pubmed/30585889", "http://www.ncbi.nlm.nih.gov/pubmed/26148985", "http://www.ncbi.nlm.nih.gov/pubmed/31753769", "http://www.ncbi.nlm.nih.gov/pubmed/31318040", "http://www.ncbi.nlm.nih.gov/pubmed/28384518", "http://www.ncbi.nlm.nih.gov/pubmed/29322820", "http://www.ncbi.nlm.nih.gov/pubmed/29555354" ], "ideal_answer": [ "Salzburg EEG criteria are used to diagnose Nonconvulsive Status Epilepticus." ], "exact_answer": [ "Nonconvulsive Status Epilepticus" ], "type": "factoid", "id": "5e48bf5ed14c9f295d000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Reevaluation of the Critically Ill Patients With Nonconvulsive Status Epilepticus by Using Salzburg Consensus Criteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322820", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "OBJECTIVE: We aimed to assess the usefulness of the Salzburg Consensus Criteria (SCC) for determining the prognosis of critically ill patients with nonconvulsive status epilepticus (NCSE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322820", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1464, "text": "CONCLUSION AND SIGNIFICANCE: Our findings suggest that SCC is highly compatible with clinical practice in the decision for treatment of patients with NCSE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322820", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 435, "text": "Clinical presentations and the Salzburg EEG criteria for NCSE were used to identify patients with NCSE after CSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29555354", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 569, "text": "EEGs recorded in the ICU were classified using the Salzburg criteria for NCSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28384518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: a retrospective study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "BACKGROUND: Several EEG criteria have been proposed for diagnosis of non-convulsive status epilepticus (NCSE), but none have been clinically validated. We aimed to assess the diagnostic accuracy of the EEG criteria proposed by a panel of experts at the fourth London-Innsbruck Colloquium on Status Epilepticus in Salzburg, 2013 (henceforth called the Salzburg criteria).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1242, "text": "Two raters blinded to all other patient data retrospectively analysed the EEG recordings and, using the Salzburg criteria, categorised patients as in NCSE or not in NCSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "abstract" }, { "offsetInBeginSection": 2835, "offsetInEndSection": 3023, "text": "INTERPRETATION: The Salzburg criteria for diagnosis of NCSE have high diagnostic accuracy and excellent inter-rater agreement, making them suitable for implementation in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus--approach to clinical application.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26092326", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "BACKGROUND: Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26092326", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1777, "text": "The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26148985", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1244, "text": "Two raters blinded to all other patient data retrospectively analysed the EEG recordings and, using the Salzburg criteria, categorised patients as in NCSE or not in NCSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Nonconvulsive Status Epilepticus: Validating the Salzburg Criteria Against an Expert EEG Examiner.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30585889", "endSection": "title" }, { "offsetInBeginSection": 2841, "offsetInEndSection": 3029, "text": "INTERPRETATION\n\nThe Salzburg criteria for diagnosis of NCSE have high diagnostic accuracy and excellent inter-rater agreement, making them suitable for implementation in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 434, "text": "Clinical presentations and the Salzburg EEG criteria for NCSE were used to identify patients with NCSE after CSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29555354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The difficulty of diagnosing NCSE in clinical practice; external validation of the Salzburg criteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31318040", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "To improve the diagnostic accuracy of electroencephalography (EEG) criteria for nonconvulsive status epilepticus (NCSE), external validation of the recently proposed Salzburg criteria is paramount.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31318040", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 437, "text": "Clinical presentations and the Salzburg EEG criteria for NCSE were used to identify patients with NCSE after CSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29555354", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 962, "text": "We divided the patients into those who were finally with diagnosed NCSE (NCSE-p) and those who were not (non-NCSE) according to the Salzburg Diagnostic EEG criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31753769", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 379, "text": "We performed an external, retrospective, diagnostic accuracy study of the Salzburg criteria, using EEG recordings from patients with and without a clinical suspicion of having NCSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31318040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26092326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "To improve the diagnostic accuracy of electroencephalography (EEG) criteria for nonconvulsive status epilepticus (NCSE), external validation of the recently proposed Salzburg criteria is paramount.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31318040", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 380, "text": "We performed an external, retrospective, diagnostic accuracy study of the Salzburg criteria, using EEG recordings from patients with and without a clinical suspicion of having NCSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31318040", "endSection": "abstract" }, { "offsetInBeginSection": 2826, "offsetInEndSection": 3014, "text": "INTERPRETATION: The Salzburg criteria for diagnosis of NCSE have high diagnostic accuracy and excellent inter-rater agreement, making them suitable for implementation in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 940, "text": "We divided the patients into those who were finally with diagnosed NCSE (NCSE-p) and those who were not (non-NCSE) according to the Salzburg Diagnostic EEG criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31753769", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1222, "text": "Two raters blinded to all other patient data retrospectively analysed the EEG recordings and, using the Salzburg criteria, categorised patients as in NCSE or not in NCSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27571157", "endSection": "abstract" } ] }, { "body": "List the components of the COMPASS complex", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29785026", "http://www.ncbi.nlm.nih.gov/pubmed/25706881", "http://www.ncbi.nlm.nih.gov/pubmed/29404406", "http://www.ncbi.nlm.nih.gov/pubmed/25189621" ], "ideal_answer": [ "MLL4\nMLL3\nWDR5\nRBBP5\nASH2\nSET1" ], "exact_answer": [ [ "MLL4" ], [ "MLL3" ], [ "WDR5" ], [ "RBBP5" ], [ "ASH2" ], [ "SET1" ] ], "type": "list", "id": "5e6e4a6c51b80c9423000002", "snippets": [ { "offsetInBeginSection": 241, "offsetInEndSection": 280, "text": " Mll4 (Kmt2d), a member of the COMPASS ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29404406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29785026", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 714, "text": "H3K4 methylation in mammalian cells is carried out by COMPASS (complex of proteins associated with Set1)-like complexes that are composed of catalytic subunits such as MLL1 (mixed-lineage leukaemia 1) and multiple regulatory subunits in which WDR5 (WD40 repeat-containing protein 5), RBBP5 (retinoblastoma-binding protein 5), ASH2 (absent, small or homoeotic discs 2) and DPY30 [constituting the WRAD sub-complex (WDR5-ASH2-RBBP5-DPY30 complex)] are the major ones shared from yeast to metazoans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25706881", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1141, "text": "individual members of COMPASS, including ASH2, WDR5 and SET1 (also known as SETD1A)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189621", "endSection": "abstract" } ] }, { "body": "Has the drug Afrezza been approved by the FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26222134" ], "ideal_answer": [ "Yes, Afrezza has been approved by the FDA." ], "exact_answer": "yes", "type": "yesno", "id": "5e776c72835f4e477700000e", "snippets": [ { "offsetInBeginSection": 635, "offsetInEndSection": 908, "text": "In contrary, MannKind Corporation started developing its ultra-rapid-acting insulin Afrezza in a bold bid, probably by managing the issues in which Exubera was not successful. Afrezza has been marketed since February, 2015 by Sanofi after getting FDA approval in June 2014.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222134", "endSection": "abstract" } ] }, { "body": "Central Vein Sign is characteristic to which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28820013", "http://www.ncbi.nlm.nih.gov/pubmed/31796822", "http://www.ncbi.nlm.nih.gov/pubmed/30213803", "http://www.ncbi.nlm.nih.gov/pubmed/29369733", "http://www.ncbi.nlm.nih.gov/pubmed/29328521", "http://www.ncbi.nlm.nih.gov/pubmed/29565219", "http://www.ncbi.nlm.nih.gov/pubmed/27300318", "http://www.ncbi.nlm.nih.gov/pubmed/27834394", "http://www.ncbi.nlm.nih.gov/pubmed/31424490", "http://www.ncbi.nlm.nih.gov/pubmed/29514948", "http://www.ncbi.nlm.nih.gov/pubmed/31668125" ], "ideal_answer": [ "Central vein sign on FLAIR* magnetic resonance imaging is highly specific and sensitive for multiple sclerosis." ], "exact_answer": [ "multiple sclerosis" ], "type": "factoid", "id": "5e4601293f54159529000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28820013", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "BACKGROUND: Detection of a \"central vein sign\" (CVS) on FLAIR* magnetic resonance imaging (MRI) is highly specific and sensitive for multiple sclerosis (MS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28820013", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1426, "text": "CONCLUSION: A simplified determination of CVS in three white matter lesions on 3T FLAIR* MRI demonstrated good specificity and sensitivity and fair inter-rater reliability for a diagnosis of MS and with further study, may be a candidate for clinical application.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28820013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29328521", "endSection": "title" }, { "offsetInBeginSection": 232, "offsetInEndSection": 544, "text": "Detection of perivenular lesions in the brain (the \"central vein sign\") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29328521", "endSection": "abstract" }, { "offsetInBeginSection": 1785, "offsetInEndSection": 1924, "text": "INTERPRETATION: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29328521", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 534, "text": "Areas covered: An overview of 7T MRI applications in MS focusing on increased sensitivity for lesion detection, specificity of the central vein sign and better understanding of MS pathophysiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Value of the central vein sign at 3T to differentiate MS from seropositive NMOSD.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514948", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "OBJECTIVE: To assess the value of the central vein sign (CVS) on a clinical 3T scanner to distinguish between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514948", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1575, "text": "CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the CVS on 3T MRI accurately distinguishes patients with MS from those with seropositive NMOSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Evaluation of the Central Vein Sign as a Diagnostic Imaging Biomarker in Multiple Sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31424490", "endSection": "title" }, { "offsetInBeginSection": 387, "offsetInEndSection": 595, "text": "Objective\n\nTo evaluate the sensitivity and specificity of various central vein sign lesion criteria for differentiating MS from non-MS conditions using 3T brain MRI with various commonly used pulse sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31424490", "endSection": "abstract" }, { "offsetInBeginSection": 2518, "offsetInEndSection": 2655, "text": "The sensitivity was 68.1% and specificity was 82.9% for distinguishing MS from not MS using a 35% central vein sign proportion threshold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31424490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Importance\n\nThe central vein sign has been proposed as a specific imaging biomarker for distinguishing between multiple sclerosis (MS) and not MS, mainly based on findings from ultrahigh-field magnetic resonance imaging (MRI) studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31424490", "endSection": "abstract" }, { "offsetInBeginSection": 2823, "offsetInEndSection": 3125, "text": "Conclusions and Relevance\n\nIn this study, use of the central vein sign at 3T MRI yielded a high specificity and a moderate sensitivity in differentiating MS from not MS; international, multicenter studies may be needed to ascertain whether the central vein sign-based criteria can accurately detect MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31424490", "endSection": "abstract" }, { "offsetInBeginSection": 1556, "offsetInEndSection": 1801, "text": "Conclusion The presence of the central vein sign on susceptibility-weighted images for MS lesions improves the understanding of the periventricular distribution of MS lesions and could contribute as adjunctive diagnostic criteria for MS disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29565219", "endSection": "abstract" }, { "offsetInBeginSection": 1274, "offsetInEndSection": 1349, "text": "The central vein sign should be considered as a diagnostic biomarker in MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668125", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 247, "text": "The central vein sign has the potential to be a non-invasive, MS-specific biomarker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668125", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 511, "text": "Original articles investigating central vein sign on T2*-weighted images of patients with MS were selected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31796822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "BACKGROUND AND PURPOSE\n\nThe central vein sign is a promising MR imaging diagnostic biomarker for multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213803", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1358, "text": "The central vein sign should be considered as a diagnostic biomarker in MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "BACKGROUND AND PURPOSE The central vein sign is a promising MR imaging diagnostic biomarker for multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213803", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 336, "text": "The central vein sign ( CVS ) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27834394", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 288, "text": "Recent studies have demonstrated that patients with MS have higher proportions of white matter lesions with the central vein sign compared with those with diseases that mimic MS on MR imaging . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213803", "endSection": "abstract" }, { "offsetInBeginSection": 1556, "offsetInEndSection": 1802, "text": "Conclusion The presence of the central vein sign on susceptibility-weighted images for MS lesions improves the understanding of the periventricular distribution of MS lesions and could contribute as adjunctive diagnostic criteria for MS disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29565219", "endSection": "abstract" }, { "offsetInBeginSection": 1791, "offsetInEndSection": 1930, "text": "INTERPRETATION\nThe central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29328521", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 248, "text": "The central vein sign has the potential to be a non-invasive, MS-specific biomarker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668125", "endSection": "abstract" }, { "offsetInBeginSection": 1282, "offsetInEndSection": 1358, "text": "The central vein sign should be considered as a diagnostic biomarker in MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "The Central Vein Sign in Multiple Sclerosis Lesions Is Present Irrespective of the T2* Sequence at 3 T. BACKGROUND AND PURPOSE\nPrevious T2*-weighted magnetic resonance imaging (MRI) studies have used white matter lesion (WML) central veins to distinguish multiple sclerosis (MS) from its mimics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27300318", "endSection": "title" }, { "offsetInBeginSection": 117, "offsetInEndSection": 309, "text": "Recent studies have demonstrated that patients with MS have higher proportions of white matter lesions with the central vein sign compared with those with diseases that mimic MS on MR imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213803", "endSection": "abstract" }, { "offsetInBeginSection": 1597, "offsetInEndSection": 1757, "text": "When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29328521", "endSection": "abstract" } ] }, { "body": "Which is the catalytic activity of the protein encoded by the gene KMT2C? ", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29785026", "http://www.ncbi.nlm.nih.gov/pubmed/29762619", "http://www.ncbi.nlm.nih.gov/pubmed/28675691" ], "ideal_answer": [ "The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers." ], "exact_answer": [ "lysine methyltransferase activity" ], "type": "factoid", "id": "5e6e487151b80c9423000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29785026", "endSection": "abstract" }, { "offsetInBeginSection": 1667, "offsetInEndSection": 1698, "text": "KMT2C histone methyltransferase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29762619", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 306, "text": " lysine methyltransferase 2C (KMT2C)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28675691", "endSection": "abstract" } ] }, { "body": "Which is the most mutated gene in dilated cardiomyopathy (DCM)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17386158", "http://www.ncbi.nlm.nih.gov/pubmed/9243088", "http://www.ncbi.nlm.nih.gov/pubmed/30342008", "http://www.ncbi.nlm.nih.gov/pubmed/29800419", "http://www.ncbi.nlm.nih.gov/pubmed/16266469", "http://www.ncbi.nlm.nih.gov/pubmed/21689390", "http://www.ncbi.nlm.nih.gov/pubmed/22773734", "http://www.ncbi.nlm.nih.gov/pubmed/20497714" ], "ideal_answer": [ "The LMNA gene is the most mutated gene in dilated cardiomyopathy (DCM) and affects approximately 25% of the patients.", "Mutations in the gene encoding lamin A/C (LMNA) cause dilated cardiomyopathy", "lamin a/c gene (lmna)", "The most mutated gene in dilated cardiomyopathy (DCM) is the lamin A/C gene. Mutations in this gene are responsible for the most common form of DCM and result in a recessive form of cardiac hypertrophy. A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes dilatedCardiac b-myosin heavy chain gene (LMNA) to be mutated in 25% of patients with DCM.", "Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy)", "The most mutated gene in dilated cardiomyopathy (DCM) is the LMO2-binding protein (LMNA) gene. Mutations in the LMNA gene underlie both adult-onset and juvenile forms of DCM and result in very severe cardiac dysfunction." ], "exact_answer": [ "LMNA", "lamin A/C" ], "type": "factoid", "id": "5d374c727bc3fee31f00000d", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 140, "text": "To examine the function of the novel mutation E82K in LMNA gene identified in a Chinese family infected by dilated cardiomyopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16266469", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 155, "text": "To investigate the effect of a novel LMNA gene mutation E82K found in a Chinese family with dilated cardiomyopathy on cell cycle of HEK293 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17386158", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 117, "text": "Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20497714", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1652, "text": "CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21689390", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1283, "text": "These results demonstrate that three different branches of the MAP kinase signaling pathway with overlapping consequences are involved in the pathogenesis of cardiomyopathy caused by LMNA mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773734", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 815, "text": "cardiomyopathy caused by LMNA mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22773734", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 167, "text": " a mouse model of dilated cardiomyopathy caused by LMNA gene mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30342008", "endSection": "title" }, { "offsetInBeginSection": 219, "offsetInEndSection": 375, "text": "We investigated the involvement of desmin in the cardiomyopathy caused by the lamin A/C gene mutation using the LmnaH222P/H222P mouse model of the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30342008", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 807, "text": "To address the extent by which the observed desmin network defects contribute to the progression of LmnaH222P/H222P cardiomyopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30342008", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 898, "text": "This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN), or inflammation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29800419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "A major advance in the study of the pathogenesis of dilated cardiomyopathy (DC) has been the identification of a familial trait in a relevant proportion of cases (more than 25%), which indicates that, at least in these cases, a mutated gene is the cause of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9243088", "endSection": "abstract" } ] }, { "body": "List psychiatric diseases that are associated with Synaptosome Associated Protein 25 (snap25).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24885975", "http://www.ncbi.nlm.nih.gov/pubmed/24391914", "http://www.ncbi.nlm.nih.gov/pubmed/23732542", "http://www.ncbi.nlm.nih.gov/pubmed/27582038", "http://www.ncbi.nlm.nih.gov/pubmed/27888397" ], "ideal_answer": [ "attention-deficit/hyperactivity disorder\nbipolar\nschizophrenia" ], "exact_answer": [ [ "schizophrenia" ], [ "attention-deficit/hyperactivity disorder" ], [ "bipolar" ] ], "type": "list", "id": "5e6e5d1d51b80c9423000003", "snippets": [ { "offsetInBeginSection": 1076, "offsetInEndSection": 1201, "text": "In addition, SNAP25, RAB18, FABP5, ARF5 and LDHA, which are related genes to schizophrenia and methamphetamine sensitization,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27582038", "endSection": "abstract" }, { "offsetInBeginSection": 616, "offsetInEndSection": 756, "text": "We aimed to study a SNAP-25 gene polymorphism, which is related to many psychiatric diseases, and FMS association in this prospective study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24885975", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 884, "text": "Studies have shown a correlation between aberrant expression of the SNAP25 and a variety of brain diseases. Single nucleotide polymorphisms (SNPs) in this gene are associated with several psychiatric diseases, such as bipolar, schizophrenia, and attention-deficit/hyperactivity disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27888397", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 496, "text": "Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24391914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "SNAP-25 is a key component of the synaptic-vesicle fusion machinery, involved in several psychiatric diseases including schizophrenia and ADHD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23732542", "endSection": "abstract" } ] }, { "body": "Which type of cells protect Haematopoietic stem and progenitor cells (HSPCs) from ultraviolet-light-induced DNA damage in aquatic vertebrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29899448" ], "ideal_answer": [ "Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment to grow and are protected from ultraviolet-light-induced DNA damages by melanocytes. Mutations that lack melanocytes have normal steady-state haem atopoiesis under standard laboratory conditions while melanocytes above the stem cell niche protect HSPCs against ultraviolet- light-induced damage.", "Melanocytes protect Haematopoietic stem and progenitor cells (HSPCs) from ultraviolet-light-induced DNA damages in aquatic vertebrates.", "Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour. A melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. The melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche." ], "exact_answer": [ "melanocytes" ], "type": "factoid", "id": "5e36cf8eb5b409ea53000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1736, "text": "Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour1,2. The location of this niche varies across species, but the evolutionary pressures that drive HSPCs to different microenvironments remain unknown. The niche is located in the bone marrow in adult mammals, whereas it is found in other locations in non-mammalian vertebrates, for example, in the kidney marrow in teleost fish. Here we show that a melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. Because mutants that lack melanocytes have normal steady-state haematopoiesis under standard laboratory conditions, we hypothesized that melanocytes above the stem cell niche protect HSPCs against ultraviolet-light-induced DNA damage. Indeed, after ultraviolet-light irradiation, unpigmented larvae show higher levels of DNA damage in HSPCs, as indicated by staining of cyclobutane pyrimidine dimers and have reduced numbers of HSPCs, as shown by cmyb (also known as myb) expression. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. Our studies reveal that melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and suggest that during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29899448", "endSection": "abstract" } ] }, { "body": "Which is the primary interacting protein of BLK?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18981230", "http://www.ncbi.nlm.nih.gov/pubmed/26420661", "http://www.ncbi.nlm.nih.gov/pubmed/23555801", "http://www.ncbi.nlm.nih.gov/pubmed/23646104", "http://www.ncbi.nlm.nih.gov/pubmed/21978998" ], "ideal_answer": [ "The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling.", "Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK.", "BLK interacts with at least two of the three kinases in the B-cell/proteasome pathway, namely the transcription factor BANK1 and the chromatin-associated transcription factor 1 (CACGT1).", "Primary interacting protein of BLK (also known as BANK1)", "Primary interacting protein of BLK is Cdk1-binding protein 1 (Bik1/Nbk1).", "The genes BANK1 and BLK were recently described as associated with SLE a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically.", "BLK activity is regulated by two interacting proteins, BANK1 and BANK2.", "a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically.", "Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK. a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically.", "A The genes BANK1 and BLK were recently described as associated with SLE", "Autophagy-related gene 5 (ATG5), ATG7, B-lymphoid tyrosine kinase (BLK) and B-cell scaffold protein with ankyrin repeats 1 (BANK1) are involved in B-cell signaling;", "bank1" ], "exact_answer": [ "BANK1" ], "type": "factoid", "id": "5d387573a1e159510500000a", "snippets": [ { "offsetInBeginSection": 115, "offsetInEndSection": 253, "text": "n this study, we find that expression of Bik/Blk/Nbk is increased in human airway epithelial cells (AECs [HAECs]) in response to IFNgamma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18981230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Gene-gene interaction of ATG5, ATG7, BLK and BANK1 in systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26420661", "endSection": "title" }, { "offsetInBeginSection": 5, "offsetInEndSection": 169, "text": "Autophagy-related gene 5 (ATG5), ATG7, B-lymphoid tyrosine kinase (BLK) and B-cell scaffold protein with ankyrin repeats 1 (BANK1) are involved in B-cell signaling;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26420661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Epistatic interaction between BANK1 and BLK in rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23646104", "endSection": "title" }, { "offsetInBeginSection": 13, "offsetInEndSection": 159, "text": "ANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23646104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21978998", "endSection": "title" }, { "offsetInBeginSection": 106, "offsetInEndSection": 176, "text": "The genes BANK1 and BLK were recently described as associated with SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21978998", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1599, "text": "a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21978998", "endSection": "abstract" } ] }, { "body": "Is Protoporphyrinogen oxidase localized to the mitochondrium?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12556518", "http://www.ncbi.nlm.nih.gov/pubmed/20603160", "http://www.ncbi.nlm.nih.gov/pubmed/16621625" ], "ideal_answer": [ "Yes,\nMitochondrial targeting of human protoporphyrinogen oxidase." ], "exact_answer": "yes", "type": "yesno", "id": "5e8220e6835f4e4777000032", "snippets": [ { "offsetInBeginSection": 393, "offsetInEndSection": 525, "text": "We showed that 28 amino acids in the amino terminus of PPOX contain an independently functioning signal for mitochondrial targeting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12556518", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1084, "text": "Based on our results we propose a mechanism for protoporphyrinogen oxidase targeting to the mitochondrion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16621625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Mitochondrial targeting of human protoporphyrinogen oxidase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16621625", "endSection": "title" }, { "offsetInBeginSection": 545, "offsetInEndSection": 681, "text": "In the present study, PfPPO has been cloned, expressed and shown to be localized to the mitochondrion by immunofluorescence microscopy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20603160", "endSection": "abstract" } ] }, { "body": "How many doses of vaxchora are required?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28622736" ], "ideal_answer": [ "Vaxchora is a single-dose vaccine." ], "exact_answer": [ "one" ], "type": "factoid", "id": "5e764440c6a8763d23000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Vaxchora: A Single-Dose Oral Cholera Vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 238, "text": "To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 855, "text": "Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1166, "text": " Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1495, "text": "Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "abstract" } ] }, { "body": "What is the SLC25A20 protein transporting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29296668", "http://www.ncbi.nlm.nih.gov/pubmed/27864727", "http://www.ncbi.nlm.nih.gov/pubmed/29408889" ], "ideal_answer": [ "The carnitine/acylcarnitine transporter (CACT; SLC25A20) mediates an antiport reaction allowing entry of acyl moieties in the form of acylcarnitines into the mitochondrial matrix and exit of free carnitine." ], "exact_answer": [ "The carnitine/acylcarnitine transporter (CACT; SLC25A20) mediates an antiport reaction allowing entry of acyl moieties in the form of acylcarnitines into the mitochondrial matrix and exit of free carnitine." ], "type": "factoid", "id": "5e6e82eac6a8763d23000001", "snippets": [ { "offsetInBeginSection": 948, "offsetInEndSection": 978, "text": "carnitine translocase Slc25a20", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29408889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "The carnitine/acylcarnitine transporter (CACT; SLC25A20) mediates an antiport reaction allowing entry of acyl moieties in the form of acylcarnitines into the mitochondrial matrix and exit of free carnitine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27864727", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 969, "text": "Prominent among these targets was the mitochondrial carnitine-acylcarnitine translocase SLC25A20", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29296668", "endSection": "abstract" } ] }, { "body": "List the vaccine strains contained in Fluvirin.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28666680" ], "ideal_answer": [ "Fluvirin contains 18 mg of haemagglutinin per H1N1 vaccine strain, 17 mg of haemagglutinin per H3N2 vaccine strain, and 15 mg of haemagglutinin per B vaccine strain." ], "exact_answer": [ [ "H1N1 vaccine strain" ], [ "H3N2 vaccine strain" ], [ "B vaccine strain" ] ], "type": "list", "id": "5e7f5a18835f4e4777000013", "snippets": [ { "offsetInBeginSection": 691, "offsetInEndSection": 1254, "text": "Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 \u03bcg of haemagglutinin per H1N1 vaccine strain, 17 \u03bcg of haemagglutinin per H3N2 vaccine strain, and 15 \u03bcg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28666680", "endSection": "abstract" } ] }, { "body": "Do de novo truncating mutations in WASF1 cause cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29961568" ], "ideal_answer": [ "No, de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability." ], "exact_answer": "no", "type": "yesno", "id": "5e36d498b5b409ea53000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29961568", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 1134, "text": "Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de\u00a0novo heterozygous mutations in WASF1 cause a rare form of intellectual disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29961568", "endSection": "abstract" } ] }, { "body": "List the attenuated live viruses contained in the Fluzone intradermal quadrivalent vaccine.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27457797" ], "ideal_answer": [ "The Fluzone Intradermal Quadrivalent vaccine contains 9 ug hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata)." ], "exact_answer": [ [ "strain of A/H1N1" ], [ "strain of A/H3N2" ], [ "B Victoria lineage" ], [ "B Yamagata lineage" ] ], "type": "list", "id": "5e7f5b43835f4e4777000014", "snippets": [ { "offsetInBeginSection": 322, "offsetInEndSection": 569, "text": "In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9\u00a0\u00b5g hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27457797", "endSection": "abstract" } ] }, { "body": "Which kinases are inhibited by Pyrotinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28498781", "http://www.ncbi.nlm.nih.gov/pubmed/30382184", "http://www.ncbi.nlm.nih.gov/pubmed/28115222", "http://www.ncbi.nlm.nih.gov/pubmed/27541626", "http://www.ncbi.nlm.nih.gov/pubmed/30341682" ], "ideal_answer": [ "Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer." ], "exact_answer": [ [ "EGFR" ], [ "HER2" ] ], "type": "list", "id": "5e44baaa48dab47f2600001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30382184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Pyrotinib is an irreversible dual pan-ErbB receptor tyrosine kinase inhibitor developed for the treatment of HER2-positive advanced solid tumours. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30341682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The discovery and development of a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor SHR1258 (pyrotinib) for the treatment of HER2-postive breast cancer is presented. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28115222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Purpose This phase I study assessed the safety, tolerability, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28498781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Pyrotinib is a novel irreversible tyrosine kinase inhibitor developed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27541626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30382184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28115222", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The discovery and development of a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor SHR1258 (pyrotinib) for the treatment of HER2-postive breast cancer is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28115222", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 924, "text": "Overall, the potent and selective EGFR/HER2 dual inhibitor, pyrotinib, displayed robust anti-tumor effects on HER2-overexpressing xenograft models and sufficiently safety windows in animals as well as favorable pharmacokinetic properties in human, which substantially ensures current clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28115222", "endSection": "abstract" } ] }, { "body": "Which bacteria causes rat bite fever?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9486709", "http://www.ncbi.nlm.nih.gov/pubmed/29912693", "http://www.ncbi.nlm.nih.gov/pubmed/18061376", "http://www.ncbi.nlm.nih.gov/pubmed/17223620", "http://www.ncbi.nlm.nih.gov/pubmed/28322713", "http://www.ncbi.nlm.nih.gov/pubmed/20619014", "http://www.ncbi.nlm.nih.gov/pubmed/7360458", "http://www.ncbi.nlm.nih.gov/pubmed/11064988", "http://www.ncbi.nlm.nih.gov/pubmed/21292904", "http://www.ncbi.nlm.nih.gov/pubmed/7707673", "http://www.ncbi.nlm.nih.gov/pubmed/11943086", "http://www.ncbi.nlm.nih.gov/pubmed/27809782", "http://www.ncbi.nlm.nih.gov/pubmed/29644421" ], "ideal_answer": [ "Rat bite fever is caused by Streptobacillus moniliformis. Infection induces typical but not pathognomonic clinical signs, such as local purulent wound infection followed by maculopapular exanthema, myalgia as well as purulent joint infections." ], "exact_answer": [ "Streptobacillus moniliformis" ], "type": "factoid", "id": "5e30fa32fbd6abf43b000048", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Rat bite fever due to Streptobacillus moniliformis induces typical but not pathognomonic clinical signs, such as local purulent wound infection followed by maculopapular exanthema, myalgia as well as purulent joint infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "[Infections after bite wounds : For example rat bite fever due to Streptobacillus moniliformis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644421", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Rat-Bite Fever in Human with Streptobacillus notomytis Infection, Japan.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29912693", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "We report a case of rat-bite fever in a 94-year-old woman with Streptobacillus notomytis infection. We established an epidemiologic link between exposure to rats and human infection by performing nested PCRs that detected S. notomytis in the intraoral swab specimens obtained from rats captured in the patient's house.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29912693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Acute Tetraplegia Caused by Rat Bite Fever in Snake Keeper and Transmission of Streptobacillus moniliformis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28322713", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "We report acute tetraplegia caused by rat bite fever in a 59-year old man (snake keeper) and transmission of Streptobacillus moniliformis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28322713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "BACKGROUND: The Leptotrichiaceae are a family of fairly unnoticed bacteria containing both microbiota on mucous membranes as well as significant pathogens such as Streptobacillus moniliformis, the causative organism of streptobacillary rat bite fever. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27809782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "BACKGROUND\n\nThe Leptotrichiaceae are a family of fairly unnoticed bacteria containing both microbiota on mucous membranes as well as significant pathogens such as Streptobacillus moniliformis, the causative organism of streptobacillary rat bite fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27809782", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 169, "text": "One of the two etiological agents that cause rat bite fever is Streptobacillus moniliformis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18061376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Rat bite fever is a rare infection typically caused by Streptobacillus moniliformis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11064988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Rat bite fever and Streptobacillus moniliformis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17223620", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Rat bite fever, caused by Streptobacillus moniliformis, is a systemic illness classically characterized by fever, rigors, and polyarthralgias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17223620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Streptobacillus moniliformis is a Gram-negative bacterium found in various laboratory animal species and is the cause of rat bite fever and Haverhill fever in man", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11943086", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 397, "text": "The bacterium was identified as Streptobacillus moniliformis , the agent of rat-bite fever", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7360458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Streptobacillus moniliformis ( Sm) , the causative agent of rat-bite fever and Haverhill fever in man , is also a pathogen in certain laboratory and domestic animals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7707673", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "The Leptotrichiaceae are a family of fairly unnoticed bacteria containing both microbiota on mucous membranes as well as significant pathogens such as Streptobacillus moniliformis , the causative organism of streptobacillary rat bite fever", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27809782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Rat bite fever due to Streptobacillus moniliformis induces typical but not pathognomonic clinical signs , such as local purulent wound infection followed by maculopapular exanthema , myalgia as well as purulent joint infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Streptobacillus moniliformis is a fastidious growing Gram-negative bacillus responsible of rat-bite fever", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21292904", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 95, "text": "Infections after bite wounds : For example rat bite fever due to Streptobacillus moniliformis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644421", "endSection": "title" }, { "offsetInBeginSection": 77, "offsetInEndSection": 170, "text": "One of the two etiological agents that cause rat bite fever is Streptobacillus moniliformis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18061376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Rat bite fever due to Streptobacillus moniliformis induces typical but not pathognomonic clinical signs, such as local purulent wound infection followed by maculopapular exanthema, myalgia as well as purulent joint infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Rat-bite fever is an uncommon bacterial illness resulting from infection with Streptobacillus moniliformis that is often transmitted by the bite of a rat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9486709", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 348, "text": "We determined that he had bacteraemia caused by a Streptobacillus moniliformis infection, which led to the development of an illness called rat bite fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20619014", "endSection": "abstract" } ] }, { "body": "What is the role of Gata3 in Th2 cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27053161", "http://www.ncbi.nlm.nih.gov/pubmed/16456016", "http://www.ncbi.nlm.nih.gov/pubmed/21632975", "http://www.ncbi.nlm.nih.gov/pubmed/27878828", "http://www.ncbi.nlm.nih.gov/pubmed/23232398", "http://www.ncbi.nlm.nih.gov/pubmed/20554961", "http://www.ncbi.nlm.nih.gov/pubmed/12835475", "http://www.ncbi.nlm.nih.gov/pubmed/19933870", "http://www.ncbi.nlm.nih.gov/pubmed/17111354", "http://www.ncbi.nlm.nih.gov/pubmed/21536806", "http://www.ncbi.nlm.nih.gov/pubmed/11135577" ], "ideal_answer": [ "RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression.", "Gata3 coordinates the progression of H3K9me2/H3K27me3 by mediating histone deacetylation and chromatin remodeling in Th2 cells. Gata3 plays an important role in this process by repressing the expression of histone H3 in Th1 cells and by promoting chromatin condensation during DNA damage-induced DNA damage.", "RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes. posttranslational modifications of Gata3 that control the regulation of IFNg expression in memory Th2 cells.", "GATA3 is responsible for induction of T(h)2 differentiation and represses T(h)1 differentiation. Posttranslational modifications of Gata3 control the regulation of IFNg expression in memory Th2 cells." ], "type": "summary", "id": "5d36c0e37bc3fee31f00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27878828", "endSection": "title" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1137, "text": "RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27878828", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 978, "text": "posttranslational modifications of Gata3 that control the regulation of IFN\u03b3 expression in memory Th2 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27053161", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 342, "text": "GATA3 is responsible for induction of T(h)2 differentiation and represses T(h)1 differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21632975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21536806", "endSection": "title" }, { "offsetInBeginSection": 187, "offsetInEndSection": 379, "text": " IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21536806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23232398", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "T-bet and GATA3 regulate the CD4+ T cell Th1/Th2 cell fate decision but little is known about the interplay between these factors outside of the murine Ifng and Il4/Il5/Il13 loci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23232398", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 952, "text": "We propose these aspects of T-bet and GATA3 function are important for Th1/Th2 differentiation and for understanding transcription factor interactions in other T cell lineage decisions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23232398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "T helper 2 cells regulate inflammatory responses to helminth infections while also mediating pathological processes of asthma and allergy. IL-4 promotes Th2 development by inducing the expression of the GATA3 transcription factor, and the Th2 phenotype is stabilized by a GATA3-dependent autoregulatory loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20554961", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 90, "text": "Type I IFN reverses human Th2 commitment and stability by suppressing GATA3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20554961", "endSection": "title" }, { "offsetInBeginSection": 826, "offsetInEndSection": 975, "text": "Our results suggest that the balance of Runx3 and GATA3 is one factor that influences the manifestation of CD4(+) cells as the Th1 or Th2 phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933870", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 729, "text": "Moreover, the expression of the Th2 transcription factor, GATA3, was significantly reduced in PKCtheta-deficient T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17111354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Impaired GATA3-dependent chromatin remodeling and Th2 cell differentiation leading to attenuated allergic airway inflammation in aging mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16456016", "endSection": "title" }, { "offsetInBeginSection": 856, "offsetInEndSection": 935, "text": "In addition, reduced expression of GATA3 was detected in developing Th2 cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16456016", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 568, "text": "transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12835475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11135577", "endSection": "title" } ] }, { "body": "Describe the Disambiguate algorithm and its application in next generation sequencing data", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27990269" ], "ideal_answer": [ "Grafting of cell lines and primary tumours is a crucial step in the drug development process between cell line studies and clinical trials. Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate.", "Grafting of cell lines and primary tumours is a crucial step in the drug development process between cell line studies and clinical trials. Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate.", "Disambiguate is an open-source application for disambiguating two species in next generation sequencing data from grafted samples. The method is based on an iterative Bayesian approach which uses sequence alignment information from germline genotype data to identify putative cis-regulatory elements which may be involved in the regulation of gene expression. The input to the method is a set of sequence elements known to be of interest to the genomics research community, and the outputs are calls for inclusion of putative regulatory elements such as enhancers, transcription factor binding sites, enhancers and enhancers", "Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples.", "Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate." ], "type": "summary", "id": "5e37183cb5b409ea53000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Disambiguate: An open-source application for disambiguating two species in next generation sequencing data from grafted samples.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1092, "text": "Grafting of cell lines and primary tumours is a crucial step in the drug development process between cell line studies and clinical trials. Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 262, "text": "Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 852, "text": "Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 445, "text": "Disambiguate operates on alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Disambiguate: An open-source application for disambiguating two species in next generation sequencing data from grafted samples", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "title" }, { "offsetInBeginSection": 140, "offsetInEndSection": 263, "text": "Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 868, "text": "Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1093, "text": "Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 461, "text": "Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 867, "text": "Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 460, "text": "Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27990269", "endSection": "abstract" } ] }, { "body": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9150551", "http://www.ncbi.nlm.nih.gov/pubmed/7875209", "http://www.ncbi.nlm.nih.gov/pubmed/31729904", "http://www.ncbi.nlm.nih.gov/pubmed/22117198", "http://www.ncbi.nlm.nih.gov/pubmed/26207883", "http://www.ncbi.nlm.nih.gov/pubmed/17919656", "http://www.ncbi.nlm.nih.gov/pubmed/12529926", "http://www.ncbi.nlm.nih.gov/pubmed/10721489", "http://www.ncbi.nlm.nih.gov/pubmed/25586702", "http://www.ncbi.nlm.nih.gov/pubmed/17543136", "http://www.ncbi.nlm.nih.gov/pubmed/26641849", "http://www.ncbi.nlm.nih.gov/pubmed/22351665", "http://www.ncbi.nlm.nih.gov/pubmed/16305803", "http://www.ncbi.nlm.nih.gov/pubmed/11001671", "http://www.ncbi.nlm.nih.gov/pubmed/10924857" ], "ideal_answer": [ "Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance,", " Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance,", "Yes, ICAMS, Intracellular Adhesion Molecules, are part of the immunoglobulin superfamily.", "yes, Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance,", "Yes, Intracellular Adhesion Molecules (ICAMS) are part of the immunoglobulin superfamily.", "Intercellular adhesion molecules (ICAMs) are members of the immunoglobulin super-family which are present on the surface of endothelial cells.", "Yes, ICAMs (Intracellular Adhesion Molecules) are a subset of the immunoglobulin superfamily.", "Yes, Intracellular Adhesion Molecules (ICAMs) are part of the immunoglobulin superfamily.", "It has now been shown that adhesion molecules, particularly those of the immunoglobulin super family (e.g. ICAM-1, VCAM-1 and PECAM-1), Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance," ], "exact_answer": "yes", "type": "yesno", "id": "5e64ed381af46fc130000015", "snippets": [ { "offsetInBeginSection": 425, "offsetInEndSection": 560, "text": "It has now been shown that adhesion molecules, particularly those of the immunoglobulin super family (e.g. ICAM-1, VCAM-1 and PECAM-1),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12529926", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 452, "text": " Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22117198", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 548, "text": "Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26207883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Intracellular adhesion molecule 1 (ICAM-1) is an adhesion-related molecule belonging to the immunoglobulin superfamily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11001671", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1131, "text": "Immunologically important integrin ligands are the intercellular adhesion molecules (ICAMs), immunoglobulin superfamily members present on inflamed endothelium and antigen-presenting cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17543136", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 603, "text": "The intercellular adhesion molecules (ICAMs) are members of the immunoglobulin superfamily and have been identified to play major roles in inflammation and immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26641849", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 598, "text": "The intercellular adhesion molecules (ICAMs) are members of the immunoglobulin superfamily and have been identified to play major roles in inflammation and immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26641849", "endSection": "abstract" }, { "offsetInBeginSection": 2046, "offsetInEndSection": 2184, "text": "ICAM-1 is a member of immunoglobulin-like superfamily of adhesion molecules that binds LFA-1 to mediate leukocytes adhesion and migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31729904", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1132, "text": "Immunologically important integrin ligands are the intercellular adhesion molecules (ICAMs), immunoglobulin superfamily members present on inflamed endothelium and antigen-presenting cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17543136", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 925, "text": "The immunoglobulin superfamily includes leukocyte function antigen-2 (LFA-2 or CD2), leukocyte function antigen-3 (LFA-3 or CD58), intercellular adhesion molecules (ICAMs), vascular adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PE-CAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9150551", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 548, "text": "The main ligand binding site of LFA-1 is the I-domain, which recognizes intercellular adhesion molecules (ICAMs), members of the immunoglobulin superfamily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17919656", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 292, "text": "Intercellular adhesion molecules (ICAMs) are structurally related members of the immunoglobulin supergene family and are ligands for the beta2 integrin molecules present on leukocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10924857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Intercellular adhesion molecules (ICAMs) belong to the immunoglobulin superfamily and participate in diverse cellular processes including host-pathogen interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25586702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM-1), participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22351665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM- 1), strongly participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16305803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Intercellular adhesion molecule-3 (ICAM-3, CD50), a member of the immunoglobulin gene superfamily, is a major ligand for the lymphocyte function-associated antigen 1 (LFA-1, CD18/CD11a) in the resting immune system and plays a role as a signaling and costimulatory molecule on T lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7875209", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 804, "text": "Expression of the immunoglobulin superfamily molecules MUC18/MCAM and ICAM-1 are associated with primary tumors and metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10721489", "endSection": "abstract" } ] }, { "body": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30261193" ], "ideal_answer": [ "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatmen", "Yes, there is evidence to suggest that traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment.", "Yes, traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment, as determined by studies in humans and in animal models.", "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment", "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment." ], "exact_answer": "yes", "type": "yesno", "id": "5e57fa23b761aafe09000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261193", "endSection": "title" }, { "offsetInBeginSection": 1512, "offsetInEndSection": 1667, "text": " Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261193", "endSection": "title" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1673, "text": "CONCLUSION\n\nUsing TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261193", "endSection": "abstract" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1673, "text": "CONCLUSION\nUsing TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261193", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1432, "text": "CONCLUSION: Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261193", "endSection": "abstract" }, { "offsetInBeginSection": 1440, "offsetInEndSection": 1594, "text": "Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261193", "endSection": "abstract" } ] }, { "body": "What receptor is associated with the protein encoded by the Sp\u00e4tzle gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30146479", "http://www.ncbi.nlm.nih.gov/pubmed/8124709", "http://www.ncbi.nlm.nih.gov/pubmed/31088910", "http://www.ncbi.nlm.nih.gov/pubmed/7590233", "http://www.ncbi.nlm.nih.gov/pubmed/11536362", "http://www.ncbi.nlm.nih.gov/pubmed/30308293", "http://www.ncbi.nlm.nih.gov/pubmed/30361090" ], "ideal_answer": [ "Currently, as a ligand for the Toll-1 receptor, only Spatzle (Spz) has been identified and characterized.", "Currently Spatzle (Spz) has been identified and characterized as a ligand for the Toll-1 receptor", "Spatzle (Spz) is the toll-1 receptor gene encoding a protein subunit of a multisubunit membrane protein complex that plays a central role in the remodeling of the cytoskeleton and its association with the membrane.", "The Drosophila Toll-1 receptor is involved in embryonic development, innate immunity, and tissue homeostasis. Currently, as a ligand for the Toll-1 receptor, only Spatzle ( Spz) has been identified and characterized." ], "exact_answer": [ "Toll-1 receptor" ], "type": "factoid", "id": "5e5e502a1af46fc13000000a", "snippets": [ { "offsetInBeginSection": 102, "offsetInEndSection": 319, "text": " In Drosophila, apoptotic elimination of the weaker \"loser\" cells from growing wing discs is induced by\u00a0a signaling module consisting of the Toll ligand Sp\u00e4tzle (Spz), several Toll-related receptors, and NF-\u03baB factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30146479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The Drosophila Toll-1 receptor is involved in embryonic development, innate immunity, and tissue homeostasis. Currently, as a ligand for the Toll-1 receptor, only Sp\u00e4tzle (Spz) has been identified and characterized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30361090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "The Drosophila gene Sp\u00e4tzle encodes the activating ligand for the Toll receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11536362", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 531, "text": "The ligand for the Toll receptor is thought to be sp\u00e4tzle (spz), a secreted protein that is activated by proteolytic cleavage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7590233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Sp\u00e4tzle protein is an extracellular ligand of Toll receptor in Toll signaling pathway involved in the embryonic dorsoventral patterning and in the innate immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308293", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 348, "text": "sp\u00e4tzle acts immediately upstream of the membrane protein Toll in the genetic pathway, suggesting that sp\u00e4tzle could encode the ventrally localized ligand that activates the receptor activity of Toll.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8124709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The Drosophila gene Sp\u00e4tzle encodes the activating ligand for the Toll receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11536362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "The Drosophila gene Sp\u00e4tzle encodes the activating ligand for the Toll receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11536362", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 401, "text": "The canonical Toll receptor (Toll-1) is activated by the cytokine Sp\u00e4tzle (Spz-1), but Drosophila encodes eight other Toll genes and five other Spz genes whose interactions with one another and associated functions are less well-understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31088910", "endSection": "abstract" } ] }, { "body": "List targeted genome editing methodologies", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25417547", "http://www.ncbi.nlm.nih.gov/pubmed/27390654" ], "ideal_answer": [ "Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome.", "Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome. Targeted genome editing (TALEN) was recently introduced as a method to manipulate eukaryotic genomes in a targeted manner with high efficiency and specificity.", "Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome. The choice of genome editing tool should be determined by the desired genome editing outcome. Such a rational approach is likely to benefit research outputs for groups working in fields as diverse as modification of cell lines, to animal models for disease studies, or gene therapy strategies." ], "exact_answer": [ [ "CRISPR/Cas9" ], [ "TALENs" ] ], "type": "list", "id": "5e35c75d158f994d3a000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "TALEN and CRISPR/Cas9-mediated genome editing in the early-branching metazoan Nematostella vectensis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25417547", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 808, "text": "Non-bilaterian phyla represent key lineages for exploring the evolutionary history of early animals. However, despite an increasing number of sequenced genomes from early-branching metazoans, efficient and reproducible methodologies for analysis of gene function remain a major challenge. Here we report the utilization of the TALEN and CRISPR/Cas9 systems to induce targeted mutations and homologous recombination-mediated transgenesis in the sea anemone Nematostella vectensis. We also present a new method to isolate genetically modified animals using engineered selection cassettes introduced by homologous recombination. Taken together, these methods will permit sophisticated gain- and loss-of-function analyses in Nematostella and perhaps other early metazoan species that allow for zygotic injection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25417547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Comparison of CRISPR/Cas9 and TALENs on editing an integrated EGFP gene in the genome of HEK293FT cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27390654", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1494, "text": "Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome. To date few comparative studies have been carried out to investigate the difference of genome editing characteristics between CRISPR/Cas9 and TALENs. While the CRISPR/Cas9 system has overtaken TALENs as the tool of choice for most research groups working in this field, we hypothesized that there could be certain applications whereby the application of TALENs would have specific benefits. Here we compare CRISPR/Cas9 and TALEN as tools for introducing site-specific editing events at an integrated EGFP gene in the genome of HEK293FT cells.RESULTS: Guide RNAs and TALEN pairs were designed to target two loci within the EGFP gene. We found that paired Cas9 nucleases induced targeted genomic deletion more efficiently and precisely than two TALEN pairs. However, when concurrently supplied with a plasmid template spanning the two DNA double-strand breaks (DSBs) within EGFP, TALENs stimulated homology directed repair (HDR) more efficiently than CRISPR/Cas9 and caused fewer targeted genomic deletions.CONCLUSIONS: Our data suggest that the choice of genome editing tool should be determined by the desired genome editing outcome. Such a rational approach is likely to benefit research outputs for groups working in fields as diverse as modification of cell lines, to animal models for disease studies, or gene therapy strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27390654", "endSection": "abstract" } ] }, { "body": "Is PTEN a tumour suppressor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29858604", "http://www.ncbi.nlm.nih.gov/pubmed/29460925" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "type": "yesno", "id": "5e6df5b51af46fc130000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "PTEN is a potent tumour suppressor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29858604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Genomic aberrations of the PTEN tumour suppressor gene are among the most common in prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29460925", "endSection": "abstract" } ] }, { "body": "Which is the function of the PRDM9 protein in mammals?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22162947", "http://www.ncbi.nlm.nih.gov/pubmed/23618393", "http://www.ncbi.nlm.nih.gov/pubmed/20044539", "http://www.ncbi.nlm.nih.gov/pubmed/27362481", "http://www.ncbi.nlm.nih.gov/pubmed/24604780", "http://www.ncbi.nlm.nih.gov/pubmed/25894966" ], "ideal_answer": [ "PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.", "Here, we demonstrate that a major player for hotspot specification is the Prdm9 gene. In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 ( PRDM9). In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots. Developmental progress of germ cells through meiotic phases is closely tied to ongoing meiotic recombination.", "In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination.", "Developmental progress of germ cells through meiotic phases is closely tied to ongoing meiotic recombination. In mammals, recombination preferentially occurs in genomic regions known as hotspots; the protein that activates these hotspots is PRDM9,. In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots.", "in mammals , recombination preferentially occurs in genomic regions known as hotspots. the protein that activates these hotspots is prdm9", "meiotic recombination" ], "type": "summary", "id": "5d3840257bc3fee31f000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Developmental progress of germ cells through meiotic phases is closely tied to ongoing meiotic recombination. In mammals, recombination preferentially occurs in genomic regions known as hotspots; the protein that activates these hotspots is PRDM9,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25894966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots. Their locations are predominantly determined by the zinc finger protein PRDM9, which binds to DNA in hotspots", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24604780", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 266, "text": "Meiotic recombination ensures proper segregation of homologous chromosomes and creates genetic variation. In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 (PRDM9)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23618393", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1617, "text": "These results, which provide the first detailed mapping of PRDM9 binding to DNA and, to our knowledge, the most detailed analysis yet of DNA binding by a long zinc-finger array, make clear that the binding specificities of PRDM9, and possibly other long-array zinc-finger proteins, are unusually complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23618393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20044539", "endSection": "title" }, { "offsetInBeginSection": 93, "offsetInEndSection": 179, "text": " Here, we demonstrate that a major player for hotspot specification is the Prdm9 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20044539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "During mammalian meiosis, double-strand breaks are deliberately made throughout the genome and then repaired, leading to the exchange of genetic material between copies of chromosomes. How the locations of breaks are specified was largely unknown until a fortuitous confluence of statistical genetics and molecular biology uncovered the role of PRDM9, a DNA binding protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22162947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27362481", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1876, "text": "These results, together with the fact that PRDM9 is the only known mammalian histone methyltransferase with both H3K4 and H3K36 trimethylation activity, suggest that trimethylation of H3K36 plays an important role in the recombination process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27362481", "endSection": "abstract" } ] }, { "body": "Which graph database is used by the Reactome graph database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29377902" ], "ideal_answer": [ "Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery.", "The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%.", "The Reactome graph database organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic biomolecular pathways and presents them using a powerful web-based graphical interface. The data are stored in a relational database, Neo4j, which is updated regularly with the addition of new data and corrections to previous data.", "The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%. The web service built on top of the graph database provides programmatic access to Reactome data by object oriented queries, but also supports more complex queries that take advantage of the new underlying graph-based data storage." ], "exact_answer": [ "Neo4j" ], "type": "factoid", "id": "5e30b870fbd6abf43b000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1401, "text": "Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its main priorities is to provide easy and efficient access to its high quality curated data. At present, biological pathway databases typically store their contents in relational databases. This limits access efficiency because there are performance issues associated with queries traversing highly interconnected data. The same data in a graph database can be queried more efficiently. Here we present the rationale behind the adoption of a graph database (Neo4j) as well as the new ContentService (REST API) that provides access to these data. The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%. The web service built on top of the graph database provides programmatic access to Reactome data by object oriented queries, but also supports more complex queries that take advantage of the new underlying graph-based data storage. By adopting graph database technology we are providing a high performance pathway data resource to the community. The Reactome graph database use case shows the power of NoSQL database engines for complex biological data types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29377902", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 834, "text": "The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29377902", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 835, "text": "The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29377902", "endSection": "abstract" } ] }, { "body": "What is the route of administration of vaxchora?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28622736" ], "ideal_answer": [ "Vaxchora is an oral vaccine." ], "exact_answer": [ "Oral" ], "type": "factoid", "id": "5e76436cc6a8763d23000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Vaxchora: A Single-Dose Oral Cholera Vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 238, "text": "To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 855, "text": "Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1495, "text": "Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622736", "endSection": "abstract" } ] }, { "body": "What is the target of the drug remdesivir?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29511076", "http://www.ncbi.nlm.nih.gov/pubmed/30275474" ], "ideal_answer": [ "remdesivir is a polymerase inhibitor" ], "exact_answer": [ "polymerase" ], "type": "factoid", "id": "5e6de3f21af46fc130000022", "snippets": [ { "offsetInBeginSection": 230, "offsetInEndSection": 430, "text": "We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511076", "endSection": "abstract" }, { "offsetInBeginSection": 2517, "offsetInEndSection": 2790, "text": " Together, these studies define the target of GS-5734 activity and demonstrate that resistance is difficult to select, only partial, and impairs fitness and virulence of MHV and SARS-CoV, supporting further development of GS-5734 as a potential effective pan-CoV antiviral.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511076", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 281, "text": " In non-human primates, early initiation of polymerase inhibitors favipiravir and remdesivir improves survival, but whether they could be effective in patients is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30275474", "endSection": "abstract" } ] }, { "body": "What is known about EphA2 in drug resistance?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30055288", "http://www.ncbi.nlm.nih.gov/pubmed/28966234", "http://www.ncbi.nlm.nih.gov/pubmed/29048432", "http://www.ncbi.nlm.nih.gov/pubmed/25963923", "http://www.ncbi.nlm.nih.gov/pubmed/26744526" ], "ideal_answer": [ "ligand- and tyrosine kinase-independent EphA2 signaling (the noncanonical pathway) promotes tumor survival and metastasis and controls acquired drug resistance and maintenance of cancer stem cell-like properties.\nFindings confirm EPHA2 as an actionable drug target, provide a rational basis for drug combination approaches, and indicate that chemical proteomics is broadly applicable for the discovery of kinase inhibitor resistance." ], "type": "summary", "id": "5e81d6c6835f4e4777000030", "snippets": [ { "offsetInBeginSection": 760, "offsetInEndSection": 1040, "text": "Existing research points to the potential use of various Eph/ephrin members as biomarkers for assessing prognosis and selecting the most suitable therapeutic strategies in variable clinical scenarios, also for overcoming drug resistance, in the era of breast cancer heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30055288", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 793, "text": "increased levels of the previously reported resistance mediators, receptor tyrosine kinase ephrine receptor A2 (EPHA2) and the hepatocyte growth factor receptor MET were also identified", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29048432", "endSection": "abstract" }, { "offsetInBeginSection": 571, "offsetInEndSection": 783, "text": "ligand- and tyrosine kinase-independent EphA2 signaling (the noncanonical pathway) promotes tumor survival and metastasis and controls acquired drug resistance and maintenance of cancer stem cell-like properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28966234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26744526", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Chemical Proteomics Uncovers EPHA2 as a Mechanism of Acquired Resistance to Small Molecule EGFR Kinase Inhibition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963923", "endSection": "title" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1435, "text": "These findings confirm EPHA2 as an actionable drug target, provide a rational basis for drug combination approaches, and indicate that chemical proteomics is broadly applicable for the discovery of kinase inhibitor resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963923", "endSection": "abstract" } ] }, { "body": "How is Slc22a3 imprinted?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30268152", "http://www.ncbi.nlm.nih.gov/pubmed/18988810", "http://www.ncbi.nlm.nih.gov/pubmed/25918552", "http://www.ncbi.nlm.nih.gov/pubmed/11562346", "http://www.ncbi.nlm.nih.gov/pubmed/11845212", "http://www.ncbi.nlm.nih.gov/pubmed/12853484", "http://www.ncbi.nlm.nih.gov/pubmed/16204191" ], "ideal_answer": [ "Two novel imprinted genes, Slc22a2 and Slc22a3 are described here that lie 110 and 155 kb 3' to Igf2r and that are not overlapped by the Air transcript but are regulated by the Igf2r-ICE, as previously shown for Igf2r. A bidirectional silencer for a 400-kilobase region that contains three imprinted, maternally expressed protein-coding genes (Igf2r/Slc22a2/Slc22a3) has been shown by targeted deletion to be located in a sequence of 3.7 kilobases, which also contains the promoter for the imprinted, paternally expressed non-coding Air RNA. Silencing of the paternal allele of three imprinted genes (Igf2r, Slc22a2 and Slc22a3) requires cis expression of the Air RNA", "cis expression of the air rna", "Silencing of the paternal allele of three imprinted genes (Igf2r, Slc22a2 and Slc22a3) requires cis expression of the Air RNA.", "Epigenetic mechanisms restrict the expression of imprinted genes to one parental allele in diploid cells. At the Igf2r/Air imprinted cluster on mouse chromosome 17, paternal-specific expression of the Air noncoding RNA has been shown to silence three genes in cis: Igf2r, Slc22a2, and Slc22a3. " ], "type": "summary", "id": "5d3802a27bc3fee31f00000e", "snippets": [ { "offsetInBeginSection": 271, "offsetInEndSection": 489, "text": "Two novel imprinted genes, Slc22a2 and Slc22a3 are described here that lie 110 and 155 kb 3' to Igf2r and that are not overlapped by the Air transcript but are regulated by the Igf2r-ICE, as previously shown for Igf2r.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11562346", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 451, "text": "A bidirectional silencer for a 400-kilobase region that contains three imprinted, maternally expressed protein-coding genes (Igf2r/Slc22a2/Slc22a3) has been shown by targeted deletion to be located in a sequence of 3.7 kilobases, which also contains the promoter for the imprinted, paternally expressed non-coding Air RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11845212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Silencing of the paternal allele of three imprinted genes (Igf2r, Slc22a2 and Slc22a3) requires cis expression of the Air RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12853484", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 912, "text": " These results exclude a role for the Igf2r promoter and for transcriptional overlap between Igf2r and Air in silencing Air, Slc22a2 and Slc22a3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12853484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Epigenetic mechanisms restrict the expression of imprinted genes to one parental allele in diploid cells. At the Igf2r/Air imprinted cluster on mouse chromosome 17, paternal-specific expression of the Air noncoding RNA has been shown to silence three genes in cis: Igf2r, Slc22a2, and Slc22a3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16204191", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 532, "text": "Air is required for allele-specific silencing of the cis-linked Slc22a3, Slc22a2, and Igf2r genes in mouse placenta. We show that Air interacts with the Slc22a3 promoter chromatin and the H3K9 histone methyltransferase G9a in placenta. Air accumulates at the Slc22a3 promoter in correlation with localized H3K9 methylation and transcriptional repression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18988810", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 673, "text": "One imprinted cluster includes the maternally expressed Igf2r, Slc22a2, and Slc22a3 genes and the paternally expressed long non-coding RNA (lncRNA) Airn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25918552", "endSection": "abstract" }, { "offsetInBeginSection": 1992, "offsetInEndSection": 2315, "text": "Our study thus provides the best candidate factor for establishing paternal silencing of marsupial IGF2R without transcriptional overlap, which is distinct from the Igf2r silencing mechanism of Airn, but which may be analogous to the mode of action for the flanking Slc22a2 and Slc22a3 gene silencing in the mouse placenta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30268152", "endSection": "abstract" } ] }, { "body": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29659825" ], "ideal_answer": [ "14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Furthermore, recruitment of dimers on accumulating wild- type Tau increases its steady- state levels ostensibly by occluding access to proteases in a phosphorylated-dependent manner.", "The 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and mutant Tau proteins.", "14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant.", "14-3-3 dimers have two contrasting effects on Tau phosphorylation: (i) they increase the rate of Tau is phosphorylated by cAMP-dependent protein kinase and (ii) they prevent the relaxation of the autophagic state of Tau.", "Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Moreover, 14-3-3 elevation itself is not pathogenic, but recruitment of dimers on accumulating wild-type Tau increases its steady-state levels ostensibly by occluding access to proteases in a phosphorylation-dependent manner.", "Neurodegenerative dementias collectively known as Tauopathies involve aberrant phosphorylation and aggregation of the neuronal protein Tau. The largely neuronal 14-3-3 proteins are also elevated in the central nervous system (CNS) and cerebrospinal fluid of Tauopathy patients, suggesting functional linkage. Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Moreover, 14-3-3 elevation itself is not pathogenic, but recruitment of dimers on accumulating wild-type Tau increases its steady-state levels ostensibly by occluding access to proteases in a phosphorylation-dependent manner. In contrast, the R406W mutant, which lacks a putative 14-3-3 binding site, responds differentially to elevation of each 14-3-3 isoform. Although excess 14-3-3z stabilizes the mutant protein, elevated D14-3-3e has a destabilizing effect probably because of altered 14-3-3 dimer composition.", "Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Moreover, 14-3-3 elevation itself is not pathogenic, but recruitment of dimers on accumulating wild-type Tau increases its steady-state levels ostensibly by occluding access to proteases in a phosphorylation-dependent manner. In contrast, the R406W mutant, which lacks a putative 14-3-3 binding site, responds differentially to elevation of each 14-3-3 isoform. Although excess 14-3-3z stabilizes the mutant protein, elevated D14-3-3e has a destabilizing effect probably because of altered 14-3-3 dimer composition.", "Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant." ], "type": "summary", "id": "5e3e8b1c48dab47f26000008", "snippets": [ { "offsetInBeginSection": 495, "offsetInEndSection": 1366, "text": "Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Moreover, 14-3-3 elevation itself is not pathogenic, but recruitment of dimers on accumulating wild-type Tau increases its steady-state levels ostensibly by occluding access to proteases in a phosphorylation-dependent manner. In contrast, the R406W mutant, which lacks a putative 14-3-3 binding site, responds differentially to elevation of each 14-3-3 isoform. Although excess 14-3-3\u03b6 stabilizes the mutant protein, elevated D14-3-3\u025b has a destabilizing effect probably because of altered 14-3-3 dimer composition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29659825", "endSection": "abstract" } ] }, { "body": "Is the tyrosine kinase BTK implicated in autoimmunity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22383797", "http://www.ncbi.nlm.nih.gov/pubmed/23136880", "http://www.ncbi.nlm.nih.gov/pubmed/23672610", "http://www.ncbi.nlm.nih.gov/pubmed/26341110", "http://www.ncbi.nlm.nih.gov/pubmed/26209625", "http://www.ncbi.nlm.nih.gov/pubmed/9730885", "http://www.ncbi.nlm.nih.gov/pubmed/27669440", "http://www.ncbi.nlm.nih.gov/pubmed/19687229" ], "ideal_answer": [ "Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn-/- mice. Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant.", "Yes, Bruton's tyrosine kinase (BTK) is implicated in autoimmunity.", "Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Bt", "Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant. Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity", "yes, BTK Signaling in B Cell Differentiation and Autoimmunity", "Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity.", "Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant.", "Yes, variants of the tyrosine kinase BTK may be implicated in autoimmunity.", "Yes, tyrosine kinase BTK is implicated in autoimmunity." ], "exact_answer": "yes", "type": "yesno", "id": "5d387098a1e1595105000006", "snippets": [ { "offsetInBeginSection": 739, "offsetInEndSection": 913, "text": "Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn-/- mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9730885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19687229", "endSection": "title" }, { "offsetInBeginSection": 549, "offsetInEndSection": 811, "text": "Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383797", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 437, "text": "Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23136880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23672610", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Tight control of B cell differentiation into plasma cells (PCs) is critical for proper immune responses and the prevention of autoimmunity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26209625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "BTK Signaling in B Cell Differentiation and Autoimmunity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26341110", "endSection": "title" }, { "offsetInBeginSection": 640, "offsetInEndSection": 712, "text": "BTK function in B cells in the context of host defense and autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26341110", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1098, "text": "promising effects of BTK inhibition were also seen in experimental animal models for lupus and rheumatoid arthritis, BTK may be a good target for controlling autoreactive B cells in patients with systemic autoimmune disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26341110", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 513, "text": "Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27669440", "endSection": "abstract" } ] }, { "body": "What is the BioPlex network?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26186194", "http://www.ncbi.nlm.nih.gov/pubmed/29054129", "http://www.ncbi.nlm.nih.gov/pubmed/27552850" ], "ideal_answer": [ "Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. BioPlex contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors.", "BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors." ], "type": "summary", "id": "5e35d7cd158f994d3a000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "The BioPlex Network: A Systematic Exploration of the Human Interactome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26186194", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1204, "text": "Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26186194", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 638, "text": "The BioPlex network is a comprehensive map of human protein interactions and represents the first phase of a long-term effort to profile the entire human ORFEOME collection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552850", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 823, "text": "BioPlex is a large-scale interactome data set based on AP-MS of baits from the human ORFeome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29054129", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 644, "text": "The BioPlex network is a comprehensive map of human protein interactions and represents the first phase of a long-term effort to profile the entire human ORFEOME collection . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552850", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 639, "text": "The BioPlex network is a comprehensive map of human protein interactions and represents the first phase of a long-term effort to profile the entire human ORFEOME collection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27552850", "endSection": "abstract" } ] }, { "body": "Which algorithm has been developed for detecting expansions of tandem repeats?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28887402" ], "ideal_answer": [ "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. For that purpose, ExpansionHunter has been developed as a software tool that, using PCR-free WGS short- read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length.", "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. ExpansionHunter has been developed as a tool which using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions." ], "exact_answer": [ "ExpansionHunter" ], "type": "factoid", "id": "5e36d5b9b5b409ea53000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1549, "text": "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2786/2789, 95% CI [0.997, 1.00]) of the wild-type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples in which every sample had one of eight different pathogenic repeat expansions, including those associated with fragile X syndrome, Friedreich's ataxia, and Huntington's disease, and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887402", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 518, "text": "We developed a software tool called ExpansionHunter that , using PCR-free WGS short-read data , can genotype repeats at the locus of interest , even if the expanded repeat is larger than the read length", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28887402", "endSection": "abstract" } ] }, { "body": "Which clotting factor is in the Andexxa?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30013295", "http://www.ncbi.nlm.nih.gov/pubmed/30362966", "http://www.ncbi.nlm.nih.gov/pubmed/30053385", "http://www.ncbi.nlm.nih.gov/pubmed/29926311", "http://www.ncbi.nlm.nih.gov/pubmed/30459509" ], "ideal_answer": [ "Andexxa(r) is a first-in-class recombinant modified factor Xa protein. It is available to reverse life-threatening or uncontrolled bleeding with the factor Xa inhibitors apixaban and rivaroxaban." ], "exact_answer": [ "Xa" ], "type": "factoid", "id": "5e319617fbd6abf43b000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Intravenous andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo; Andexxa\u00ae] is a first-in-class recombinant modified factor Xa protein that has been developed by Portola Pharmaceuticals as a universal antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29926311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Fostamatinib (Tavalisse) for thrombocytopenia in adults with chronic immune thrombocytopenia; coagulation factor Xa (recombinant), inactivated-zhzo (Andexxa) for the reversal of anticoagulation; epoetin alfa-epbx (Retacrit), a biosimilar for the treatment of anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30013295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A New Option for Reversing the Anticoagulant Effect of Factor Xa Inhibitors: Andexanet Alfa (ANDEXXA).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053385", "endSection": "title" }, { "offsetInBeginSection": 450, "offsetInEndSection": 778, "text": "Andexanet alfa was approved in May 2018, under the brand name ANDEXXA, for the reversal of 2 of FXa inhibitors, apixaban and rivaroxaban, when life-threatening or uncontrolled bleeding occurs. This accelerated approval was based on change in anti-FXa activity from baseline that indicated a reversal of the anticoagulant effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Andexanet Alfa for Reversing Factor Xa Inhibition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30362966", "endSection": "title" }, { "offsetInBeginSection": 424, "offsetInEndSection": 652, "text": "Andexanet alfa (Andexxa\u00ae, Portola Pharmaceuticals, San Francisco, CA) is a modified form of factor Xa that acts as a decoy binding entity for DOACs, thereby allowing endogenous factor Xa to perform its normal clotting functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30362966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 461, "text": "Andexanet alfa (Andexxa\u00ae), a first-in-class recombinant modified factor Xa protein, is currently the only specific agent available to reverse life-threatening or uncontrolled bleeding with the factor Xa inhibitors apixaban and rivaroxaban. Andexanet alfa acts as a decoy and competes with endogenous factor Xa to bind factor Xa inhibitors, thereby reversing the anticoagulant effects of factor Xa inhibitors, and restoring the activity of endogenous factor Xa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459509", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 677, "text": "Andexanet alfa (Andexxa, Portola Pharmaceuticals, San Francisco, CA) is a modified form of factor Xa that acts as a decoy binding entity for DOACs, thereby allowing endogenous factor Xa to perform its normal clotting functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30362966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Andexanet alfa (Andexxa __sup__ \u00ae __end_sup__ ), a first-in-class recombinant modified factor Xa protein, is currently the only specific agent available to reverse life-threatening or uncontrolled bleeding with the factor Xa inhibitors apixaban and rivaroxaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Intravenous andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo; Andexxa __sup__ \u00ae __end_sup__ ] is a first-in-class recombinant modified factor Xa protein that has been developed by Portola Pharmaceuticals as a universal antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29926311", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 642, "text": "Andexanet alfa was approved in May 2018, under the brand name ANDEXXA, for the reversal of 2 of FXa inhibitors, apixaban and rivaroxaban, when life-threatening or uncontrolled bleeding occurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Andexanet alfa (Andexxa \u00ae ), a first-in-class recombinant modified factor Xa protein, is currently the only specific agent available to reverse life-threatening or uncontrolled bleeding with the factor Xa inhibitors apixaban and rivaroxaban.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459509", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 678, "text": "Andexanet alfa (Andexxa, Portola Pharmaceuticals, San Francisco, CA) is a modified form of factor Xa that acts as a decoy binding entity for DOACs, thereby allowing endogenous factor Xa to perform its normal clotting functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30362966", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 643, "text": "Andexanet alfa was approved in May 2018, under the brand name ANDEXXA, for the reversal of 2 of FXa inhibitors, apixaban and rivaroxaban, when life-threatening or uncontrolled bleeding occurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Intravenous andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo; Andexxa\u00ae] is a first-in-class recombinant modified factor Xa protein that has been developed by Portola Pharmaceuticals as a universal antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29926311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Fostamatinib (Tavalisse) for thrombocytopenia in adults with chronic immune thrombocytopenia; coagulation factor Xa (recombinant), inactivated-zhzo (Andexxa) for the reversal of anticoagulation; epoetin alfa-epbx (Retacrit), a biosimilar for the treatment of anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30013295", "endSection": "abstract" } ] }, { "body": "How are nucleosome posisitions correlated with sites of 5'-methyl-cytosine (5mC) or 5-hydroxy-methyl-cytosine (5hmC)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25263161", "http://www.ncbi.nlm.nih.gov/pubmed/24812327", "http://www.ncbi.nlm.nih.gov/pubmed/22196727", "http://www.ncbi.nlm.nih.gov/pubmed/25506399", "http://www.ncbi.nlm.nih.gov/pubmed/26832418" ], "ideal_answer": [ "We find that Mbd3 and Brg1 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy. outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes we have investigated nucleosome organization around hypomethylated regions (HMRs)", "Nucleosomes are enriched at hypomethylated region (HMR) boundaries. The mostly unmethylated CpG islands have reduced nucleosome occupancy. Outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes.", "Using this global approach, we observe the dependency of nucleosome positioning upon the 5'-methyl-cytosine (5mC) methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosomic positioning and 5-hydroxymethylation at CTCF regions that is not present at promoters. Transcription, histone modifications, and DNA methylation alter this \"ground state\"", "outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes" ], "type": "summary", "id": "5d38542b7bc3fee31f000015", "snippets": [ { "offsetInBeginSection": 253, "offsetInEndSection": 468, "text": "We find that Mbd3 and Brg1 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy. Furthermore, both Mbd3 and Brg1 play key roles in the biology of 5-hydroxymethylcytosine (5hmC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22196727", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 593, "text": " 5-hydroxymethylcytosine (5hmC) is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26832418", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1333, "text": " In both cell types, we find that nucleosomes are enriched at HMR boundaries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506399", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 981, "text": "we have investigated nucleosome organization around hypomethylated regions (HMRs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506399", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 615, "text": "The mostly unmethylated CpG islands have reduced nucleosome occupancy ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24812327", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 947, "text": "outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24812327", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1253, "text": "DNA containing 5hmC is more likely to be incorporated into nucleosomes. Once formed, the 5hmC nucleosomes might be in an open and transcriptionally active state due to the weakened interaction of hydroxymethylated DNA with the H2A-H2B dimers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263161", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the drug LONSURF?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28315543", "http://www.ncbi.nlm.nih.gov/pubmed/31002008", "http://www.ncbi.nlm.nih.gov/pubmed/29177842", "http://www.ncbi.nlm.nih.gov/pubmed/28213365", "http://www.ncbi.nlm.nih.gov/pubmed/26609205", "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "http://www.ncbi.nlm.nih.gov/pubmed/30350179", "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "http://www.ncbi.nlm.nih.gov/pubmed/27568360", "http://www.ncbi.nlm.nih.gov/pubmed/28977993" ], "ideal_answer": [ "Lonsurf includes trifluridine and tipiracil. It is a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride) presents a new treatment option for metastatic colorectal cancer patients refractory or intolerant to standard therapies." ], "exact_answer": [ [ "trifluridine" ], [ "tipiracil" ] ], "type": "list", "id": "5e4b52e36d0a27794100001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "The National Institute for Health and Care Excellence (NICE) invited Servier, the company manufacturing trifluridine and tipiracil (T/T; trade name: Lonsurf\u00ae), to submit evidence for the clinical and cost effectiveness of T/T compared with best supportive care (BSC) for metastatic colorectal cancer (third-line or later).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "PURPOSE: Trifluridine/tipiracil (FTD/TPI; TAS-102, Lonsurf\u00ae), a novel form of chemotherapy for metastatic colorectal cancer (mCRC), has shown clinical benefit in the global, phase III RECOURSE trial, regardless of patient age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30350179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "BACKGROUND: Trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 370, "text": "These AEs may affect patient adherence, particularly with completely oral regimens, such as trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), an antimetabolite agent for patients with mCRC refractory or intolerant to standard therapies.\u2029", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28315543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "The FDA approved TAS-102 (Lonsurf; Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF biological therapy; and if RAS wild type, an anti-EGFR therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28213365", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 816, "text": "Here we show that tumoroid cultures from a CRC patient are highly sensitive to the thymidylate synthase inhibitor 5-fluorouracil (adrucil) but less sensitive to the combination of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (Lonsurf).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28977993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Trifluridine/tipiracil (Lonsurf(\u00ae)) is a novel, orally active, antimetabolite agent comprised of trifluridine, a thymidine-based nucleoside analogue, and tipiracil, a potent thymidine phosphorylase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568360", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 352, "text": "TAS-102 (Lonsurf) is an oral fluoropyrimidine that is formed by the combination of 2 active drugs: trifluridine (a nucleoside analog) and tipiracil hydrochloride (a thymidine phosphorylase inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Trifluridine/tipiracil (Lonsurf __sup__ \u00ae __end_sup__ ) is a fixed-dose combination tablet comprising trifluridine, an antineoplastic nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "The National Institute for Health and Care Excellence (NICE) invited Servier, the company manufacturing trifluridine and tipiracil (T/T; trade name: Lonsurf __sup__ \u00ae __end_sup__ ), to submit evidence for the clinical and cost effectiveness of T/T compared with best supportive care (BSC) for metastatic colorectal cancer (third-line or later).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177842", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 868, "text": "Here we show that tumoroid cultures from a CRC patient are highly sensitive to the thymidylate synthase inhibitor 5-fluorouracil (adrucil) but less sensitive to the combination of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (Lonsurf).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28977993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Trifluridine/tipiracil (Lonsurf \u00ae ) is a fixed-dose combination tablet comprising trifluridine, an antineoplastic nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "endSection": "abstract" }, { "offsetInBeginSection": 1883, "offsetInEndSection": 2107, "text": "What is already known TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31002008", "endSection": "abstract" }, { "offsetInBeginSection": 1993, "offsetInEndSection": 2217, "text": "What is already known TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31002008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Evolocumab (Repatha) for patients with hypercholesterolemia whose condition has not been controlled by statins and other therapies; trifluridine/tipiracil (Lonsurf) for metastatic colorectal cancer; and blood coagulation factor VIII (Nuwiq) for adults and children with hemophilia A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26609205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "In May 2014 , tablets containing both trifluridine and tipiracil hydrochloride ( Lonsurf\u00ae tablets ) were launched in Japan ahead of other countries , for the treatment of advanced/relapsed unresectable colorectal cancer . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "Trifluridine/tipiracil ( TAS-102 , Lonsurf\u00ae) , a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue ( trifluridine , FTD ) with a thymidine phosphorylase inhibitor ( tipiracil hydrochloride , TPI ) presents a new treatment option for metastatic colorectal cancer ( mCRC ) patients refractory or intolerant to standard therapies . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Evolocumab ( Repatha ) for patients with hypercholesterolemia whose condition has not been controlled by statins and other therapies; trifluridine/tipiracil ( Lonsurf ) for metastatic colorectal cancer; and blood coagulation factor VIII ( Nuwiq ) for adults and children with hemophilia A .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26609205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Trifluridine/tipiracil ( Lonsurf(\u00ae) ) is a novel , orally active , antimetabolite agent comprised of trifluridine , a thymidine-based nucleoside analogue , and tipiracil , a potent thymidine phosphorylase inhibitor . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "The National Institute for Health and Care Excellence ( NICE ) invited Servier , the company manufacturing trifluridine and tipiracil ( T/T; trade name: Lonsurf) , to submit evidence for the clinical and cost effectiveness of T/T compared with best supportive care ( BSC ) for metastatic colorectal cancer ( third-line or later) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29177842", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Trifluridine/tipiracil ( Lonsurf ) is a fixed-dose combination tablet comprising trifluridine , an antineoplastic nucleoside analogue , and tipiracil , a thymidine phosphorylase inhibitor . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 361, "text": "TAS-102 ( Lonsurf ) is an oral fluoropyrimidine that is formed by the combination of 2 active drugs: trifluridine ( a nucleoside analog ) and tipiracil hydrochloride ( a thymidine phosphorylase inhibitor) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 370, "text": "These AEs may affect patient adherence , particularly with completely oral regimens , such as trifluridine/tipiracil ( TAS-102 , Lonsurf\u00ae) , an antimetabolite agent for patients with mCRC refractory or intolerant to standard therapies . .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28315543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Trifluridine/tipiracil ( FTD/TPI; TAS-102 , Lonsurf\u00ae) , a novel form of chemotherapy for metastatic colorectal cancer ( mCRC) , has shown clinical benefit in the global , phase III RECOURSE trial , regardless of patient age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30350179", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 353, "text": "TAS-102 (Lonsurf) is an oral fluoropyrimidine that is formed by the combination of 2 active drugs: trifluridine (a nucleoside analog) and tipiracil hydrochloride (a thymidine phosphorylase inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "BACKGROUND\nTrifluridine/tipiracil (TAS-102, Lonsurf\u00ae), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf\u00ae tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf\u00ae tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "BACKGROUND: Trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 31, "text": "Trifluridine/tipiracil (Lonsurf", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "Trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standard therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "endSection": "abstract" } ] }, { "body": "What is 23andMe?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28629370", "http://www.ncbi.nlm.nih.gov/pubmed/30452341", "http://www.ncbi.nlm.nih.gov/pubmed/29469551", "http://www.ncbi.nlm.nih.gov/pubmed/27449572", "http://www.ncbi.nlm.nih.gov/pubmed/22616356", "http://www.ncbi.nlm.nih.gov/pubmed/20415555", "http://www.ncbi.nlm.nih.gov/pubmed/18852208", "http://www.ncbi.nlm.nih.gov/pubmed/29998537" ], "ideal_answer": [ "We first take a look at how personal genomics services, exemplified by the company 23andMe,", "23andMe is a genetic testing company which offers personal genetic services." ], "type": "summary", "id": "5e7cbf1b835f4e4777000012", "snippets": [ { "offsetInBeginSection": 123, "offsetInEndSection": 151, "text": "gave genetics company 23andM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30452341", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 222, "text": "we examine three personal genomics companies--Navigenics, deCODEme and 23andMe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22616356", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 251, "text": "personal genomics services, exemplified by the company 23andMe,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20415555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The past year has been marked by the emergence of several companies, such as 23andMe, deCODEME,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18852208", "endSection": "abstract" }, { "offsetInBeginSection": 1979, "offsetInEndSection": 2116, "text": "Nevertheless, DTC companies like 23andMe act as a powerful intermediate step to integrate pharmacogenetic testing into clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Pharmacogenetic testing through the direct-to-consumer genetic testing company 23andMe.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629370", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 343, "text": "Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "PURPOSE\n\n23andMe is back on the market as the first direct-to-consumer genetic testing company that \"includes reports that meet Food and Drug Administration (FDA) standards\u2026.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27449572", "endSection": "abstract" }, { "offsetInBeginSection": 42, "offsetInEndSection": 94, "text": "The case of 23andMe online genetic testing platform.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29998537", "endSection": "title" }, { "offsetInBeginSection": 124, "offsetInEndSection": 338, "text": "Direct-to-consumer ( DTC ) genetic testing companies , such as 23andMe , allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The past year has been marked by the emergence of several companies , such as 23andMe , deCODEME , Navigenics and Knome , offering tests using genome-wide technology direct to consumers over the internet. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18852208", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 791, "text": "More recently , it placed burdensome restrictions on direct-to-consumer ( DTC ) genetic testing companies , such as 23andMe , based on fears that consumers would make irrational medical decisions after receiving genetic variant results . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29469551", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 343, "text": "Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629370", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 331, "text": "Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629370", "endSection": "abstract" } ] }, { "body": "Is induction of interferon by TLR7 higher in males?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18088248" ], "ideal_answer": [ "Yes. TLR7 activation correlates with induction of interferon more strongly in males.", "Yes. TLR7 induction of interferon is higher in males than in females.", "variations of tlr7 impair the immune response to hcv and imply a gender-specific effect", "Variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-alpha therapy." ], "exact_answer": "yes", "type": "yesno", "id": "5d387721a1e159510500000c", "snippets": [ { "offsetInBeginSection": 1588, "offsetInEndSection": 1732, "text": "ur results suggest that variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18088248", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1416, "text": "The c.32A>T variation was over-represented in female patients with chronic HCV-infection compared to patients with other chronic liver diseases and to healthy controls (P < 0.05). In contrast, c.2403 G>A was less prevalent in male patients with chronic HCV-infection (P < 0.05). No association was observed for the third variant, c.1-120T>G. Haplotype analysis confirmed the differential distribution of TLR7 variants between the groups. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-alpha therapy (P < 0.05)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18088248", "endSection": "abstract" } ] }, { "body": "Cushing's disease is associated with a tumor in what part of the body?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28413388", "http://www.ncbi.nlm.nih.gov/pubmed/22918543", "http://www.ncbi.nlm.nih.gov/pubmed/28850717", "http://www.ncbi.nlm.nih.gov/pubmed/15521676", "http://www.ncbi.nlm.nih.gov/pubmed/30148086", "http://www.ncbi.nlm.nih.gov/pubmed/31666445" ], "ideal_answer": [ "Cushing's disease is associated with a tumor in the pituitary gland", "Cushing's disease is associated with a tumor in the pituitary gland.", "Cushing's disease (CD) is a rare endocrine disorder associated with increased serum levels of cortisol secreted due to an underlying tumour in pituitary.", "Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone production from a pituitary adenoma," ], "exact_answer": [ "pituitary" ], "type": "factoid", "id": "5e669e401af46fc13000001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Cushing's disease (CD) is a rare disabling condition caused by Adrenocorticotropic hormone (ACTH)-secreting adenomas of the pituitary", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28850717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Cushing's syndrome is a rare endocrine disorder that comprises a large group of signs and symptoms resulting from chronic exposure to excess corticosteroids. Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone production from a pituitary adenoma, which is referred to as Cushing's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28413388", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "Cushing's disease (CD) is a rare endocrine disorder associated with increased serum levels of cortisol secreted due to an underlying tumour in pituitary.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30148086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Cushing's disease is primarily caused by autonomic hypersecretion of adrenocorticotropic hormone (ACTH) from a pituitary adenoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31666445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Cushing 's disease ( CD ) is a rare endocrine disorder associated with increased serum levels of cortisol secreted due to an underlying tumour in pituitary", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30148086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Hypercortisolism due to an ACTH-secreting pituitary adenoma (Cushing's disease) is a chronic condition associated with high morbidity and mortality if inadequately managed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22918543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cushing's syndrome due to an ACTH-secreting pituitary tumor is associated with serious morbidity and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15521676", "endSection": "abstract" } ] }, { "body": "Which was the first genetically modified organism (GMO) to be used as vaccine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27425792" ], "ideal_answer": [ "The first genetically modified organism to be used as vaccine was the live oral cholera vaccine CVD 103-HgR or vaxchora." ], "exact_answer": [ "Vaxchora", "CVD 103-HgR" ], "type": "factoid", "id": "5e764647c6a8763d23000016", "snippets": [ { "offsetInBeginSection": 255, "offsetInEndSection": 614, "text": "The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27425792", "endSection": "abstract" } ] }, { "body": "How does PRDM9 recognize the specific DNA motifs for meiotic recombination?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29674518", "http://www.ncbi.nlm.nih.gov/pubmed/22162947", "http://www.ncbi.nlm.nih.gov/pubmed/23618393", "http://www.ncbi.nlm.nih.gov/pubmed/29072575", "http://www.ncbi.nlm.nih.gov/pubmed/23651476", "http://www.ncbi.nlm.nih.gov/pubmed/22028627", "http://www.ncbi.nlm.nih.gov/pubmed/26351520", "http://www.ncbi.nlm.nih.gov/pubmed/28155083", "http://www.ncbi.nlm.nih.gov/pubmed/27932493", "http://www.ncbi.nlm.nih.gov/pubmed/29478809", "http://www.ncbi.nlm.nih.gov/pubmed/26840484" ], "ideal_answer": [ "The PRDM9 gene encodes a protein with a highly variable tandem-repeat zinc finger (ZF) DNA-binding domain that plays a key role in determining sequence-specific hotspots of meiotic recombination genome wide. The long zinc finger domain of PRDM9 forms a highly stable and long-lived complex with its DNA recognition sequence.", "The long zinc finger domain of PRDM9 forms a highly stable and long-lived complex with its DNA recognition sequence.", " In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 (PRDM9), a long-array zinc-finger and chromatin-modifier protein." ], "type": "summary", "id": "5d383af27bc3fee31f000010", "snippets": [ { "offsetInBeginSection": 376, "offsetInEndSection": 668, "text": "any properties of this protein remain mysterious, however, including how it binds to DNA, how it contributes to male infertility-both in humans, and in hybrid mice-and why, in spite of its fundamental function in meiosis, its binding domain varies extensively among humans and across mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22162947", "endSection": "abstract" }, { "offsetInBeginSection": 31, "offsetInEndSection": 160, "text": " in vitro DNA binding behavior of PRDM9, a zinc finger protein involved in the localization of recombination hotspots in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23651476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840484", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 409, "text": "In most mammals, the placement of genetic crossovers is determined by the binding of PRDM9, a highly polymorphic protein with a long zinc finger array, to its cognate binding sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26351520", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 936, "text": "the PRDM9 variant associated with hotspot activity binds specifically to DNA sequences located at the center of the three hotspots tested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028627", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 324, "text": " In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 (PRDM9), a long-array zinc-finger and chromatin-modifier protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23618393", "endSection": "abstract" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1617, "text": "the binding specificities of PRDM9, and possibly other long-array zinc-finger proteins, are unusually complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23618393", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 586, "text": "We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29072575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The long zinc finger domain of PRDM9 forms a highly stable and long-lived complex with its DNA recognition sequence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28155083", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "In mammals, meiotic recombination occurs at 1- to 2-kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27932493", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 283, "text": " In mice and humans, the location of these breaks is determined by the meiosis-specific protein PRDM9, through the DNA-binding specificity of its zinc-finger domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29478809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Homologous recombination is required for proper segregation of homologous chromosomes during meiosis. It occurs predominantly at recombination hotspots that are defined by the DNA binding specificity of the PRDM9 protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29674518", "endSection": "abstract" } ] }, { "body": "Which micro-RNAs (miR) are associated with the human cycloxygenase-2 (COX-2) gene promoter?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28182010", "http://www.ncbi.nlm.nih.gov/pubmed/22049153", "http://www.ncbi.nlm.nih.gov/pubmed/24616567", "http://www.ncbi.nlm.nih.gov/pubmed/29945115", "http://www.ncbi.nlm.nih.gov/pubmed/29404887", "http://www.ncbi.nlm.nih.gov/pubmed/29511456", "http://www.ncbi.nlm.nih.gov/pubmed/24472607", "http://www.ncbi.nlm.nih.gov/pubmed/29524580", "http://www.ncbi.nlm.nih.gov/pubmed/27900011", "http://www.ncbi.nlm.nih.gov/pubmed/25907560", "http://www.ncbi.nlm.nih.gov/pubmed/28678919" ], "ideal_answer": [ "MicroRNA-16, miRNA-128, miR-26b, icroRNA-26a, MicroRNA-146b-3p, microRNA-137, mi R-146a, mir-143-5p,microRNA-101, microRNAs-142-3 p, mi r-146p, mir-128 and miR -128 were found to be associated with the human cycloxygenase-2 (COX-2) gene promoter.", "miR-146a, miR-203, miRNA-124a, microRNA-155, miRS-146b, miS-146c, miG-145, miRP-148a, let-7b, siRNA-181, miRNAs-152, miN-182, mir-223, myosin heavy chain, are associated with the human cycloxygenase-2 (COX-2) gene promoter We also report the following miRNA associations with the COX- 2 gene promoters: miCENP-1,", "Recently, the human cycloxygenase-2 (COX-2) gene promoter has a microRNA (miR) promoter region that is highly expressed in non-cancer cells and is associated with the cell cycle. MicroRNA-16, miRNA-128, microRNA-26a, miRNAs-142-3p, miR-144, mi R-146b-3 p, mir-146a, icroRNA- 26a, -26b,microRNA-137, mi r-146 a, mir-143-5p,", "miR-16 was shown to bind the COX-2 3'-UTR and inhibit COX-2 expression by promoting rapid mRNA decay. miR-143-5p directly targets COX-2. The NF-kB family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2-3'-UTR. microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells. MicroRNA-144 is regulated by CP2 and decreases COX-2 expression and PGE2 production in mouse ovarian granulosa cells. The down-regulation of microRNA-137 contributes to the up-regulation of retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2 signaling. MicroRNA-128 inhibits proliferation and invasion of glioma cells by targeting COX-2. Altered expression of miR-146b-3p is closely related to the progression and development of DCMI mediating the RAF/P38MAPK/COX-2 signal transduction pathway. MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma.", "The following micro-RNAs (miRNAs) have been associated with the human cycloxygenase-2 (COX-2) gene promoter: microRNA-16, miRNA-128, micro RNA-26a, miR-142-3p, mir-144, mi r-146b-3 p, mir-16), mir-26b, icroRNA-26 a, MicroRNA-146 b-3P, mir-146a, mir -143-5p, mir microRNA-137, mir--MicroRNA" ], "exact_answer": [ [ "miR-16" ], [ "miR-143-5p" ], [ "miR-146a" ], [ "miR-26a" ], [ "miR-26b" ], [ "miR-142-3p" ], [ "miR-144" ], [ "miR-137" ], [ "miR-128" ], [ "miR-146b-3p" ], [ "miR-101" ] ], "type": "list", "id": "5d38673da1e1595105000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "The mRNA stability factor HuR inhibits microRNA-16 targeting of COX-2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22049153", "endSection": "title" }, { "offsetInBeginSection": 431, "offsetInEndSection": 538, "text": ". We identified miR-16 to bind the COX-2 3'-UTR and inhibit COX-2 expression by promoting rapid mRNA decay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22049153", "endSection": "abstract" }, { "offsetInBeginSection": 1812, "offsetInEndSection": 1930, "text": "However, miR-143-5p alone directly targets COX-2, and it exhibits a stronger tumor suppressive effect than miR-143-3p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24616567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The NF-\u03baB family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24472607", "endSection": "title" }, { "offsetInBeginSection": 231, "offsetInEndSection": 375, "text": "TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2-3'-UTR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25907560", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 163, "text": "icroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25907560", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Downregulated microRNA-26a modulates prostate cancer cell proliferation and apoptosis by targeting COX-2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27900011", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28678919", "endSection": "title" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1318, "text": " Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28678919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "MicroRNA-144 is regulated by CP2 and decreases COX-2 expression and PGE2 production in mouse ovarian granulosa cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28182010", "endSection": "title" }, { "offsetInBeginSection": 452, "offsetInEndSection": 815, "text": "overexpression of miR-144 significantly decreased the luciferase reporter activity under the control of the cyclooxygenase-2 (COX-2) or mothers against decapentaplegic homologue 4 (Smad4) 3'-untranslated region (3'-UTR) and suppressed COX-2 and Smad4 expression. In contrast, a miR-144 inhibitor increased COX-2 and Smad4 expression in mouse granulosa cells (mGCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28182010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The down-regulation of microRNA-137 contributes to the up-regulation of retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2 signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29945115", "endSection": "title" }, { "offsetInBeginSection": 532, "offsetInEndSection": 837, "text": "Bioinformatic analysis predicted that cyclooxygenase-2 (COX-2) was a potential target gene of miR-137, which was validated by a dual-luciferase reporter assay. Moreover, our results showed that miR-137 negatively regulated the expression of COX-2 and the production of prostaglandin E2 (PGE2) in RB cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29945115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "MicroRNA-128 inhibits proliferation and invasion of glioma cells by targeting COX-2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524580", "endSection": "title" }, { "offsetInBeginSection": 458, "offsetInEndSection": 750, "text": " the inhibitory effects of miR-128 mimics on the invasion and proliferation of glioma cells were reversed by overexpression of cyclooxygenase-2 (COX-2). Our data showed that COX-2 was a candidate target of miR-128. Luciferase activity of 3'-UTR of COX-2 was reduced in the presence of miR-128", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524580", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 1040, "text": "miR-128 obviously decreased COX-2 mRNA stability determined by real time PCR. Contrarily, we found that miR-128 inhibitor significantly increased the COX-2 mRNA expression, and elevated the protein expression of MMP9 and ki67, and promoted the proliferation of glioma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "MicroRNA-146b-3p regulates the development and progression of cerebral infarction with diabetes through RAF1/P38MAPK/COX-2 signaling pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511456", "endSection": "title" }, { "offsetInBeginSection": 1565, "offsetInEndSection": 1748, "text": "Our data have implied that altered expression of miR-146b-3p is closely related to the progression and development of DCMI mediating the RAF/P38MAPK/COX-2 signal transduction pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29404887", "endSection": "title" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1292, "text": "Our results suggest that modulating miR-101 and COX-2 levels or their activity may be a potential therapeutic strategy for endometrial cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29404887", "endSection": "abstract" } ] }, { "body": "What percentage of patients of nasopharyngeal carcinoma (NPC) develop recurrent disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28900497", "http://www.ncbi.nlm.nih.gov/pubmed/29290287", "http://www.ncbi.nlm.nih.gov/pubmed/28849027", "http://www.ncbi.nlm.nih.gov/pubmed/30142809", "http://www.ncbi.nlm.nih.gov/pubmed/21982471", "http://www.ncbi.nlm.nih.gov/pubmed/25607111", "http://www.ncbi.nlm.nih.gov/pubmed/25265358" ], "ideal_answer": [ "1.04% of patients with nasopharyngeal carcinoma develop recurrent disease. The overall recurrence rate is 75%.", "The overall recurrence rate was 75% in HPV negative patients and 11% in HPV positive ones. Disease recurred in a spared parotid gland in three patients (1.04%)." ], "exact_answer": [ "11-75%" ], "type": "factoid", "id": "5d3826427bc3fee31f00000f", "snippets": [ { "offsetInBeginSection": 794, "offsetInEndSection": 992, "text": "IMRT group achieved better locoregional control rate, with the 5-year locoregional relapse-free survival (LRRFS) were 84.9% and 87.7% among patients received 2D-RT and IMRT, respectively (P\u202f=\u202f0.050)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29290287", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 693, "text": "The patients were divided into the local recurrence (n\u200a=\u200a39), fibrosis (n\u200a=\u200a51), clivus recurrence (n\u200a=\u200a22), and clivus nonrecurrence (n\u200a=\u200a48) groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142809", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 872, "text": " Serum was collected from 40\u00a0patients with NPC\u00a0[recurrence\u00a0(n=20) and no recurrence\u00a0(n=20)]. Compared to non\u2011recurrent NPC\u00a0(nrNPC), we found 59\u00a0proteins to be significantly dysregulated in rNPC; most of these have been previously reported to play a role in carcinogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28849027", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 854, "text": "With a median follow up of 49.50 months, the 3- and 5- year LR-free rate were 95.43% and 94.30% respectively; the 3- and 5- year RR-free rate were 95.94% and 95.41% respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28900497", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 547, "text": "The overall recurrence rate was 75% in HPV negative patients and 11% in HPV positive ones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25265358", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 700, "text": "Disease recurred in a spared parotid gland in three patients (1.04%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21982471", "endSection": "abstract" } ] }, { "body": "What classes of drugs does Retapamulin belong to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "http://www.ncbi.nlm.nih.gov/pubmed/19436611", "http://www.ncbi.nlm.nih.gov/pubmed/22777229", "http://www.ncbi.nlm.nih.gov/pubmed/23793314", "http://www.ncbi.nlm.nih.gov/pubmed/28874907", "http://www.ncbi.nlm.nih.gov/pubmed/18041900", "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "http://www.ncbi.nlm.nih.gov/pubmed/18341664", "http://www.ncbi.nlm.nih.gov/pubmed/16940066", "http://www.ncbi.nlm.nih.gov/pubmed/28533232" ], "ideal_answer": [ "Retapamulin is a member of the pleuromutilin family of antibiotics.", "Pleuromutilins have a potential to be developed as a new class of antibiotics for use in humans. This class includes valnemulin, tiamulin, and retapamulin.", "Retapamulin belongs to the class of gentamycin-resistant antibiotics." ], "exact_answer": [ "antibiotics" ], "type": "factoid", "id": "5e5e50751af46fc13000000b", "snippets": [ { "offsetInBeginSection": 321, "offsetInEndSection": 458, "text": "Retapamulin 1% ointment is a unique topical antibiotic formulation that may be a suitable option for the treatment of clinically infected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777229", "endSection": "abstract" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1328, "text": "Retapamulin 1% is effective for the treatment of atopic dermatitis infected with S aureus, and demonstrates efficacy against both methicillin-susceptible and methicillin-resistant strains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777229", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 741, "text": "Pleuromutilins have a potential to be developed as a new class of antibiotics for systemic use in humans. In the current study, we investigated the relationship between pleuromutilins, including valnemulin, tiamulin, and retapamulin, and 13 other antibiotics representing different mechanisms of action, against methicillin-susceptible and -resistant S. aureus both in vitro and in an experimental Galleria mellonella model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874907", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 958, "text": "he eight antibiotics, azithromycin, clarithromycin, erythromycin, fusidic acid, mupirocin, retapamulin, rifampin, and telithromycin, had diverse targets and mechanisms of action. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28533232", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 435, "text": "Retapamulin belongs to a newly developed class of antibiotics for the treatment of uncomplicated skin infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18341664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Retapamulin: a newer topical antibiotic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23793314", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Retapamulin: a new topical antibiotic for the treatment of uncomplicated skin infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Retapamulin is the first agent in the new pleuromutilin class of antibacterials to become commercially available for clinical use in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically designed for use as a topical agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19436611", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 434, "text": "Retapamulin belongs to a newly developed class of antibiotics for the treatment of uncomplicated skin infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18341664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Retapamulin is a semisynthetic pleuromutilin compound with in vitroactivity against Gram-positive bacteria, no cross-resistance to other classes of antimicrobial agents in current use and a low potential for development of resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18041900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Retapamulin is a semisynthetic pleuromutilin derivative being developed as a topical antibiotic for treating bacterial infections of the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVES\n\nRetapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Retapamulin is the first agent in the new pleuromutilin class of antibacterials to become commercially available for clinical use in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically designed for use as a topical agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19436611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Retapamulin is a semisynthetic pleuromutilin derivative being developed as a topical antibiotic for treating bacterial infections of the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "In vitro activity against anaerobes of retapamulin, a new topical antibiotic for treatment of skin infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of ozanimod?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28398597", "http://www.ncbi.nlm.nih.gov/pubmed/26990079", "http://www.ncbi.nlm.nih.gov/pubmed/29608575", "http://www.ncbi.nlm.nih.gov/pubmed/31492652", "http://www.ncbi.nlm.nih.gov/pubmed/27144850", "http://www.ncbi.nlm.nih.gov/pubmed/28765121", "http://www.ncbi.nlm.nih.gov/pubmed/31492651", "http://www.ncbi.nlm.nih.gov/pubmed/30930775", "http://www.ncbi.nlm.nih.gov/pubmed/29500302", "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "http://www.ncbi.nlm.nih.gov/pubmed/26239599", "http://www.ncbi.nlm.nih.gov/pubmed/30043658", "http://www.ncbi.nlm.nih.gov/pubmed/27049060" ], "ideal_answer": [ "Ozanimod is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis." ], "type": "summary", "id": "5e44af0848dab47f26000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "abstract" }, { "offsetInBeginSection": 994, "offsetInEndSection": 1254, "text": "Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28765121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Ozanimod (RPC1063) is an oral selective modulator of the sphingosine-1-phosphate 1 and 5 receptors under development for the treatment of relapsing multiple sclerosis and inflammatory bowel disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 680, "text": "In addition, there are three more specific S1P agonists in late stages of development: siponimod, ponesimod, and ozanimod. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29500302", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608575", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The sphingosine-1-phosphate receptor-1 (S1P __sub__ 1 __end_sub__ ) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049060", "endSection": "abstract" }, { "offsetInBeginSection": 1582, "offsetInEndSection": 1831, "text": "This review will focus on SM drugs approved and under development, including JAK inhibitors (tofacitinib, filgotinib, upadacitinib, peficitinib) and S1PR agonists (KRP-203, fingolimod, ozanimod, etrasimod, amiselimod), and their mechanism of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30930775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "BACKGROUND\n\nOzanimod is a sphingosine 1-phosphate receptor modulator, which selectively binds to sphingosine 1-phosphate receptor subtypes 1 and 5 with high affinity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31492652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND\n\nOzanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31492651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The sphingosine-1-phosphate receptor-1 (S1P 1 ) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "BACKGROUND\n\nOzanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "BACKGROUND Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30043658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28398597", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The sphingosine-1-phosphate receptor-1 ( S1P ) agonist ozanimod ameliorates ulcerative colitis , yet its mechanism of action is unknown", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049060", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 981, "text": "More selective S1P receptor agents-ponesimod ( ACT128800) , siponimod ( BAF312) , ozanimod ( RPC1063) , ceralifimod ( ONO-4641) , GSK2018682 , and MT-1303-are still in relatively early stages of development , but phase I and II trials showed promising efficacy and safety", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26239599", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Ozanimod (RPC1063) is an oral selective modulator of the sphingosine-1-phosphate 1 and 5 receptors under development for the treatment of relapsing multiple sclerosis and inflammatory bowel disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28783871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "BACKGROUND\nOzanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26990079", "endSection": "title" } ] }, { "body": "What are Syndecans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25572401", "http://www.ncbi.nlm.nih.gov/pubmed/11900484", "http://www.ncbi.nlm.nih.gov/pubmed/8875948", "http://www.ncbi.nlm.nih.gov/pubmed/16620374", "http://www.ncbi.nlm.nih.gov/pubmed/29510059", "http://www.ncbi.nlm.nih.gov/pubmed/29931674", "http://www.ncbi.nlm.nih.gov/pubmed/23384311", "http://www.ncbi.nlm.nih.gov/pubmed/29226950", "http://www.ncbi.nlm.nih.gov/pubmed/15936998", "http://www.ncbi.nlm.nih.gov/pubmed/26149933" ], "ideal_answer": [ "Syndecans are transmembrane proteoglycans with heparan and chondroitin sulfate chains attached to their extracellular domain. Like many proteoglycans, they interact with a large number of ligands, such as growth factors, adhesion receptors, soluble small molecules, proteinases, and other extracellular matrix proteins to initiate downstream signaling pathways. Syndecans play a major role in inflammation, mainly by regulating leukocyte extravasation and cytokine function.", "Syndecans are important mediators of signalling by transmitting external stimuli into the cells. Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues Syndecans are transmembrane proteoglycans that, together with integrins, control cell interactions with extracellular matrix components. ", "Syndecans are transmembrane proteoglycans that, together with integrins, control cell interactions with extracellular matrix components. " ], "type": "summary", "id": "5e6e9689c6a8763d23000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Syndecans are transmembrane proteoglycans that, together with integrins, control cell interactions with extracellular matrix components. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29510059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Syndecans are cell surface heparan sulfate proteoglycans that serve as co-receptors and modulate the actions of a number of extracellular ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15936998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The syndecans are a type of cell surface adhesion receptor that initiates intracellular signaling events through receptor clustering mediated by their highly conserved transmembrane domains (TMDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25572401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "BACKGROUND\n\nThe syndecans are the major family of transmembrane proteoglycans in animals and are known for multiple roles in cell interactions and growth factor signalling during development, inflammatory response, wound-repair and tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16620374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Syndecans are transmembrane proteoglycans implicated in the regulation of cell growth and differentiation , by interacting with growth factors . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11900484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Syndecans are transmembrane heparan sulfate proteoglycans involved in the regulation of cell growth , differentiation , adhesion , neuronal development , and lipid metabolism . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Syndecans are a family of four cell surface proteoglycans that bind to various components of the extracellular environment and can regulate many cellular behaviors including growth , adhesion , and movement . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8875948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Syndecans are transmembrane heparan sulfate proteoglycans with roles in cell proliferation , differentiation , adhesion , and migration . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23384311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Syndecans are transmembrane heparan sulfate proteoglycans involved in the regulation of cell growth, differentiation, adhesion, neuronal development, and lipid metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149933", "endSection": "abstract" } ] }, { "body": "What is chemokinesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29566102", "http://www.ncbi.nlm.nih.gov/pubmed/8604012", "http://www.ncbi.nlm.nih.gov/pubmed/15274332", "http://www.ncbi.nlm.nih.gov/pubmed/21743962", "http://www.ncbi.nlm.nih.gov/pubmed/25290568", "http://www.ncbi.nlm.nih.gov/pubmed/16317716" ], "ideal_answer": [ "Chemokinesis is chemically prompted kinesis, a motile response of unicellular prokaryotic or eukaryotic organisms to chemicals that cause the cell to make some kind of change in their migratory/swimming behaviour." ], "type": "summary", "id": "5e639c051af46fc130000013", "snippets": [ { "offsetInBeginSection": 382, "offsetInEndSection": 429, "text": "chemokinesis (increase rate of cell migration) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566102", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 375, "text": "Random cell movement is generally described as chemokinesis, and represents an important step at the beginning of tumor cell liberation from the primary site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21743962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "There is still confusion about what is meant by widely used terms for cellular locomotion such as chemokinesis and random locomotion and how these are distinguished from chemotaxis . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25290568", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 433, "text": "This study demonstrates that in addition to orientation ( chemotaxis) , stimulated speed ( chemokinesis ) is an important component of the directed migration of these amoebae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16317716", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 225, "text": "Eosinophil migration in vitro can be divided into directed migration, or chemotaxis, and random migration, or chemokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8604012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "There is still confusion about what is meant by widely used terms for cellular locomotion such as chemokinesis and random locomotion and how these are distinguished from chemotaxis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25290568", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 224, "text": "Eosinophil migration in vitro can be divided into directed migration, or chemotaxis, and random migration, or chemokinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8604012", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Chemotaxis is defined as directional cell movement of cells towards concentration gradients of solubilized attractants, whereas chemokinesis is defined as random cell movement in the absence of chemoattractant gradients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15274332", "endSection": "abstract" } ] }, { "body": "What cellular process is JAK/STAT involved in?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26938566", "http://www.ncbi.nlm.nih.gov/pubmed/27928945", "http://www.ncbi.nlm.nih.gov/pubmed/26398764", "http://www.ncbi.nlm.nih.gov/pubmed/28716890", "http://www.ncbi.nlm.nih.gov/pubmed/27713030", "http://www.ncbi.nlm.nih.gov/pubmed/22284190", "http://www.ncbi.nlm.nih.gov/pubmed/28914550", "http://www.ncbi.nlm.nih.gov/pubmed/23827161", "http://www.ncbi.nlm.nih.gov/pubmed/12479803" ], "ideal_answer": [ "The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway is utilized by numerous cytokines and interferons, and is essential for the development and function of both innate and adaptive immunity.", "The serine/threonine kinase JAK/STAT is a major regulator of Janus kinase activity and plays a critical role in regulating the ubiquitin/proinflammatory signaling pathway.", "JAK/STAT is a master regulator of immunity", "JAK/STAT is involved in the regulation of immunity" ], "exact_answer": [ "inflammation" ], "type": "factoid", "id": "5e6399dd1af46fc13000000f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 202, "text": "JAK/STAT signal pathway, a requisite part in the signaling process of growth factors and cytokines, has become attractive targets for numerous immune, inflammatory and hematopoietic diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27713030", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway is utilized by numerous cytokines and interferons, and is essential for the development and function of both innate and adaptive immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27713030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Stimulation of the cholinergic inflammatory pathway can attenuate collagen-induced arthritis (CIA) and inhibit synovitis by Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28914550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28716890", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 745, "text": "Moreover , JAK/STAT signaling , especially via the IL-6/STAT3 axis , is believed to be involved in the transition of inflammatory lesions to tumors leading to colitis-associated cancer ( CAC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26938566", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1271, "text": "The JAK/STAT cascade is a principal signal transduction pathway in cytokine and growth factor signaling, regulating various cellular processes such as cell proliferation, differentiation, migration and survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26398764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway constitute the fulcrum in many vital cellular processes, including cell growth, differentiation, proliferation, and regulatory immune functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23827161", "endSection": "abstract" } ] }, { "body": "What is the link between dental x-ray and brain tumor risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22492363", "http://www.ncbi.nlm.nih.gov/pubmed/18447746", "http://www.ncbi.nlm.nih.gov/pubmed/23406732", "http://www.ncbi.nlm.nih.gov/pubmed/30661338", "http://www.ncbi.nlm.nih.gov/pubmed/2790826", "http://www.ncbi.nlm.nih.gov/pubmed/31502516", "http://www.ncbi.nlm.nih.gov/pubmed/1646072", "http://www.ncbi.nlm.nih.gov/pubmed/26094363" ], "ideal_answer": [ "There is data to suggest that dental x-ray can be associated with significantly increased risk of meningiomas and gliomas. However, some studies failed to demonstrate an association between dental x-rays and brain tumor risk." ], "type": "summary", "id": "5e323a37fbd6abf43b000057", "snippets": [ { "offsetInBeginSection": 1011, "offsetInEndSection": 1262, "text": "CONCLUSION: Our finding of a total lack of correlation between benign brain tumors and markers of oral health and, by implication, dental X-rays, suggests there may be no relationship between dental X-rays and meningioma or other benign brain tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26094363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 37, "text": "Dental x-rays and risk of meningioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492363", "endSection": "title" }, { "offsetInBeginSection": 1868, "offsetInEndSection": 2072, "text": "CONCLUSIONS: Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with an increased risk of intracranial meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492363", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 763, "text": "n the present article the authors review the literature relating to radiation-induced meningiomas (RIMs). Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18447746", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 842, "text": "Frequency of full-mouth dental X-ray examinations after age 25 related to both glioma (P for trend = 0.04) and meningioma risk (P for trend = 0.06).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2790826", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 791, "text": "In brain tumor studies, the association between dental X-ray exposure and meningioma was statistically significant in 5 of the 7 studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30661338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "BACKGROUND\n\nThis study evaluates the risk of benign brain tumors (BBTs) and malignant brain tumors (MBTs) associated with dental diagnostic X-ray, using a large population-based case-control study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406732", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1394, "text": "In a few studies examining health effects related to dental X-ray exposure, possibly increased risks of meningioma and thyroid cancer were suggested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30661338", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1099, "text": "No significant association was found between MBTs and dental diagnostic X-ray exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406732", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 367, "text": "We found a statistically significant positive association of brain cancer with reported exposure to dental X-rays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1646072", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1265, "text": "CONCLUSION\n\nOur finding of a total lack of correlation between benign brain tumors and markers of oral health and, by implication, dental X-rays, suggests there may be no relationship between dental X-rays and meningioma or other benign brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26094363", "endSection": "abstract" }, { "offsetInBeginSection": 2319, "offsetInEndSection": 2678, "text": "Prospective studies, based on dental X-ray records and patient follow-up, are needed to test the hypothesis further and clarify the possible cancer risk associated with dental radiography, as although the risk at the individual level, particularly with improved technology/equipment, is likely to be very low, the proportion of the population exposed is high.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31502516", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 806, "text": "In brain tumor studies , the association between dental X-ray exposure and meningioma was statistically significant in 5 of the 7 studies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30661338", "endSection": "abstract" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1223, "text": "CONCLUSIONS\nExposure to dental diagnostic X-rays in oral and maxillofacial care increases the risk of BBTs, but not MBTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406732", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 685, "text": "With the objective to inform clinical practice and guidelines, we synthesized the current epidemiological evidence on the association between dental X-rays and the risk of thyroid cancer, meningioma, and other cancers of the head and neck region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31502516", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 792, "text": "In brain tumor studies, the association between dental X-ray exposure and meningioma was statistically significant in 5 of the 7 studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30661338", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1395, "text": "In a few studies examining health effects related to dental X-ray exposure, possibly increased risks of meningioma and thyroid cancer were suggested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30661338", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1217, "text": "CONCLUSIONS: Exposure to dental diagnostic X-rays in oral and maxillofacial care increases the risk of BBTs, but not MBTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406732", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1261, "text": "CONCLUSION: Our finding of a total lack of correlation between benign brain tumors and markers of oral health and, by implication, dental X-rays, suggests there may be no relationship between dental X-rays and meningioma or other benign brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26094363", "endSection": "abstract" }, { "offsetInBeginSection": 1841, "offsetInEndSection": 2031, "text": "Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with an increased risk of intracranial meningioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492363", "endSection": "abstract" } ] }, { "body": "Is there a vaccine for rotavirus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22423021", "http://www.ncbi.nlm.nih.gov/pubmed/2851185", "http://www.ncbi.nlm.nih.gov/pubmed/7707626", "http://www.ncbi.nlm.nih.gov/pubmed/22796685", "http://www.ncbi.nlm.nih.gov/pubmed/16397431", "http://www.ncbi.nlm.nih.gov/pubmed/8920706", "http://www.ncbi.nlm.nih.gov/pubmed/24422678", "http://www.ncbi.nlm.nih.gov/pubmed/28442435", "http://www.ncbi.nlm.nih.gov/pubmed/27443593", "http://www.ncbi.nlm.nih.gov/pubmed/19995190", "http://www.ncbi.nlm.nih.gov/pubmed/15502699", "http://www.ncbi.nlm.nih.gov/pubmed/22702319", "http://www.ncbi.nlm.nih.gov/pubmed/26263200", "http://www.ncbi.nlm.nih.gov/pubmed/22119590", "http://www.ncbi.nlm.nih.gov/pubmed/9015114", "http://www.ncbi.nlm.nih.gov/pubmed/22431803", "http://www.ncbi.nlm.nih.gov/pubmed/19931717", "http://www.ncbi.nlm.nih.gov/pubmed/21504245", "http://www.ncbi.nlm.nih.gov/pubmed/8752295", "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "http://www.ncbi.nlm.nih.gov/pubmed/27522178", "http://www.ncbi.nlm.nih.gov/pubmed/25680314", "http://www.ncbi.nlm.nih.gov/pubmed/20661105", "http://www.ncbi.nlm.nih.gov/pubmed/30046133", "http://www.ncbi.nlm.nih.gov/pubmed/28340179", "http://www.ncbi.nlm.nih.gov/pubmed/29102168", "http://www.ncbi.nlm.nih.gov/pubmed/9949951", "http://www.ncbi.nlm.nih.gov/pubmed/31023829", "http://www.ncbi.nlm.nih.gov/pubmed/28369477" ], "ideal_answer": [ "yes, rotavirus pentavalent vaccine (RotaTeq(r)) as a sole vaccine", "Effectiveness of rotavirus pentavalent vaccine rotavirus pentavalent vaccine (RotaTeq(r)) as a sole vaccine", "safety and immunogenicity of pentavalent rotavirus vaccine (rv5 )", "Yes, there is a vaccine against rotavirus infection that is approved for Europe, Canada and Australia.", "Yes, there is a human neonatal rotavirus vaccine against serogroup B Rotavirus.", "Effectiveness of rotavirus pentavalent vaccine", "Yes, there is a 4-component vaccine against capsular rotavirus vaccine.", "Yes, there is a pentavalent vaccine for Rotavirus", "Yes, there is a human neonatal rotavirus vaccine.", "High effectiveness of RotaTeq as the sole rotavirus vaccine in a universal immunization programme was demonstrated in a high-income country.", " rotavirus pentavalent vaccine (RotaTeq(r)) as a sole vaccine" ], "exact_answer": "yes", "type": "yesno", "id": "5e64f1921af46fc130000018", "snippets": [ { "offsetInBeginSection": 38, "offsetInEndSection": 102, "text": "Safety and Immunogenicity of Pentavalent Rotavirus Vaccine (RV5)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28340179", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "This study compares the safety and immunogenicity of pentavalent rotavirus vaccine (RV5)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28340179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Effectiveness of rotavirus pentavalent vaccine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28442435", "endSection": "title" }, { "offsetInBeginSection": 22, "offsetInEndSection": 81, "text": " rotavirus pentavalent vaccine (RotaTeq\u00ae) as a sole vaccine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28442435", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 375, "text": "We describe rotavirus vaccine coverage and missed opportunities for rotavirus vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31023829", "endSection": "abstract" }, { "offsetInBeginSection": 1877, "offsetInEndSection": 2048, "text": "CONCLUSIONS\n\nAddressing missed opportunities for rotavirus vaccination is essential to achieving the 80% rotavirus vaccine coverage target outlined by Healthy People 2020.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31023829", "endSection": "abstract" }, { "offsetInBeginSection": 1734, "offsetInEndSection": 1875, "text": "Complete rotavirus vaccine coverage could be improved to 81% if all missed opportunities within the ACIP-recommended schedule were addressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31023829", "endSection": "abstract" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1194, "text": "RESULTS\n\nThe national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27522178", "endSection": "abstract" }, { "offsetInBeginSection": 1747, "offsetInEndSection": 1989, "text": "CONCLUSIONS\n\nNorway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27522178", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1679, "text": "Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26263200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26263200", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 131, "text": "US Rotavirus Vaccine Efficacy Group.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7707626", "endSection": "title" }, { "offsetInBeginSection": 284, "offsetInEndSection": 374, "text": "We describe rotavirus vaccine coverage and missed opportunities for rotavirus vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31023829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Rotavirus vaccines: a story of success.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680314", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Clinical and immunological studies of rotavirus vaccines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2851185", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Impact of rotavirus vaccine on rotavirus diarrhoea in countries of East and Southern Africa.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29102168", "endSection": "title" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1133, "text": "Rotavirus diarrheal episodes were identified by ELISA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8920706", "endSection": "abstract" }, { "offsetInBeginSection": 2032, "offsetInEndSection": 2170, "text": "The decrease in rotavirus positivity was inversely related to increase in rotavirus vaccine coverage showing impact of rotavirus vaccines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29102168", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1169, "text": "We described trends in rotavirus positivity among tested stool samples before and after rotavirus vaccine introduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29102168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The RIT 4237 bovine rotavirus vaccine has served as a useful model for rotavirus vaccination, but the vaccine will not be further developed or tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2851185", "endSection": "abstract" }, { "offsetInBeginSection": 2156, "offsetInEndSection": 2272, "text": "Only the RRV vaccine induced a low level of protection against rotavirus diarrhea mainly of serotype G1 specificity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8920706", "endSection": "abstract" }, { "offsetInBeginSection": 2543, "offsetInEndSection": 2719, "text": "It is recommended that new rotavirus vaccine candidates be developed at cheaper price to speed up the introduction of rotavirus immunization in the developing world in general.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22119590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Review of rotavirus vaccine trials in Finland.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8752295", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Risk of intussusception after monovalent rotavirus vaccination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24422678", "endSection": "title" }, { "offsetInBeginSection": 213, "offsetInEndSection": 283, "text": "Rotavirus vaccines are underused compared with other routine vaccines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31023829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "With rotavirus vaccines now available globally , it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India , in order to weigh the urgency of introducing a vaccine to help control rotavirus disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22796685", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 328, "text": "Is there evidence that rotavirus vaccines are effective in preventing acute gastroenteritis complications such as dehydration and hospitalization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22423021", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1506, "text": "With the introduction of new rotavirus vaccines in sight , rotavirus gastroenteritis may be regarded as the single most frequent vaccine-preventable disease among children in the EU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16397431", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 658, "text": "With the recent introduction of the two rotavirus vaccines , RotaTeq and Rotarix , in many countries , it appears that the total number of hospitalizations due to rotavirus infections is being reduced , at least in developed countries that implemented a universal immunization program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19995190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Change in rotavirus epidemiology in northeast Florida after the introduction of rotavirus vaccine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20661105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine , the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22431803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Impact of rotavirus vaccines on rotavirus disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22702319", "endSection": "title" }, { "offsetInBeginSection": 457, "offsetInEndSection": 630, "text": "With safe and efficacious rotavirus vaccines now on the verge of widespread adoption , researchers can be vital advocates for their uptake into routine immunization programs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19931717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Rotavirus vaccine RIX4414 (Rotarix\u2122): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developed countries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504245", "endSection": "title" }, { "offsetInBeginSection": 450, "offsetInEndSection": 633, "text": "In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programmes in the community setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504245", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 450, "text": "The monovalent rotavirus vaccine RIX4414 (Rotarix\u2122) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504245", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 844, "text": "Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination programme using RIX4414 was compared with no universal rotavirus vaccination programme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504245", "endSection": "abstract" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1716, "text": "It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504245", "endSection": "abstract" }, { "offsetInBeginSection": 1716, "offsetInEndSection": 1995, "text": "Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favourable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination programme, results were generally sensitive to vaccine costs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21504245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502699", "endSection": "title" }, { "offsetInBeginSection": 138, "offsetInEndSection": 307, "text": "A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502699", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 985, "text": "Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15502699", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 364, "text": "We describe the intussusception epidemiology prior to rotavirus vaccine, temporal association of intussusception cases to administration of rotavirus vaccine, and estimate the additional number of intussusception cases that may be associated with rotavirus vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30046133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Epidemiology of intussusception before and after rotavirus vaccine introduction in Fiji.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30046133", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "In 2012, Fiji introduced rotavirus vaccine (Rotarix, GSK) into the national immunisation schedule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30046133", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 635, "text": "Four trials of RIT 4237 bovine rotavirus vaccine, one trial of group A RRV-1 rhesus rotavirus vaccine, and one trial of rhesus-human reassortant rotavirus vaccines D x RRV and DS1 x RRV were carried out between 1983-1989.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9015114", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1248, "text": "Problems associated with the use of any oral rotavirus vaccine include acid lability of the vaccine virus, which requires buffering, and a slight but significant interference of oral poliovirus vaccine with the uptake of rotavirus vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9015114", "endSection": "abstract" }, { "offsetInBeginSection": 1249, "offsetInEndSection": 1374, "text": "In the near future, oral heterologous rotavirus vaccines may be available for prevention of severe rotavirus gastroenteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9015114", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1008, "text": "There was no apparent difference between bovine and rhesus-based rotavirus vaccines in the protective efficacy against severe rotavirus gastroenteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9015114", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 413, "text": "Efficacy studies of this vaccine in 6-12 month-old children gave results characteristic of the performance of oral rotavirus vaccines in general: 58% protective efficacy against any rotavirus gastroenteritis and 82% against \"clinically significant\" gastroenteritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9015114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Live oral rotavirus vaccine strain RIT 4237, derived from group A bovine rotavirus NCDV, was given to human volunteers in Tampere, Finland in 1982.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9015114", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 881, "text": "Targeted efforts to evaluate indirect effects of rotavirus vaccine in low income countries are required to understand the total impact of rotavirus vaccine on the global burden of rotavirus disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27443593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Widespread introduction of rotavirus vaccines has led to major reductions in the burden of rotavirus gastroenteritis worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27443593", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 682, "text": "While rotavirus vaccine indirect effects have been demonstrated in high and middle income countries, there are very little data from low income countries where force of infection, population structures and vaccine schedules differ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27443593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Measuring indirect effects of rotavirus vaccine in low income countries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27443593", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 355, "text": "To describe the cases of intussusception among rotavirus vaccine recipients reported to the Vaccine Adverse Event Reporting System from October 1998 through December 1999.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 419, "text": "Infants vaccinated with rotavirus vaccine in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 785, "text": "There were 98 confirmed cases of intussusception after vaccination with rotavirus vaccine reported to the Vaccine Adverse Event Reporting System; 60 of these developed intussusception within 1 week after vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1222, "text": "Using a passive surveillance system for vaccine adverse events, we observed at least a fourfold increase over the expected number of intussusception cases occurring within 1 week of receipt of rotavirus vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "abstract" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1333, "text": "Other studies were initiated to further define the relationship between rotavirus vaccine and intussusception.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "abstract" }, { "offsetInBeginSection": 1334, "offsetInEndSection": 1548, "text": "In light of these and other data, the rotavirus vaccine manufacturer voluntarily removed its product from the market, and the recommendation for routine use of rotavirus vaccine among US infants has been withdrawn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11389295", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 255, "text": "To review the biology, immunology, and virology of rotavirus infections and describe the efforts towards the construction of vaccines using human and animal rotaviruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9949951", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 511, "text": "In August 1998 the Food and Drug Administration in the United States approved the licensure of a rotavirus vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9949951", "endSection": "abstract" } ] }, { "body": "Which T-UCR has been implicated in prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29212226" ], "ideal_answer": [ "Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer ( CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance.", "The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. Overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020)." ], "exact_answer": [ "Uc.63+" ], "type": "factoid", "id": "5e36a718b5b409ea53000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1758, "text": "Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC. Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020). These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 688, "text": "Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1774, "text": "These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "title" }, { "offsetInBeginSection": 566, "offsetInEndSection": 696, "text": "Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 689, "text": "Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" } ] }, { "body": "Is BNN20 involved in Parkinson's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28461162" ], "ideal_answer": [ "Yes. Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). BNN-20 has been suggested as an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway, mimicking the action of the endogenous neurotrophin BDNF. Thus BNN-20 could be proposed for treatment of PD.", "Yes. BNN20 is an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway that has been implicated in numerous pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis and Parkinson's disease.", "Yes. BNN20 is involved in the development of Parkinson's disease. It is a member of the intramembrane-tumor necrosis factor-a (ITF-a) family of transcription factors that are dysregulated in several neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal degeneration, axonal injury, late-onset cerebellar ataxia, and multiple sclerosis.", "Yes. BNN20 could be proposed as a therapeutic for PD. BNN-20 administration to Weaver/NGL mice induced a strong NF-kB-dependent transcriptional response in the brain as detected by bioluminescence imaging, which was abolished by co-administration of the TrkB inhibitor ANA-12" ], "exact_answer": "yes", "type": "yesno", "id": "5e2d7ceefbd6abf43b00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1853, "text": "Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). However, in most cases, they cannot readily cross the human blood-brain-barrier (BBB). Herein, we propose as a therapeutic for PD the small molecule 17-beta-spiro-[5-androsten-17,2'-oxiran]-3beta-ol (BNN-20), a synthetic analogue of DHEA, which crosses the BBB and is deprived of endocrine side-effects. Using the \"weaver\" mouse, a genetic model of PD, which exhibits progressive dopaminergic neurodegeneration in the Substantia Nigra (SN), we have shown that long-term administration (P1-P21) of BNN-20 almost fully protected the dopaminergic neurons and their terminals, via i) a strong anti-apoptotic effect, probably mediated through the Tropomyosin receptor kinase B (TrkB) neurotrophin receptor's PI3K-Akt-NF-\u03baB signaling pathway, ii) by exerting an efficient antioxidant effect, iii) by inducing significant anti-inflammatory activity and iv) by restoring Brain-Derived Neurotrophic Factor (BDNF) levels. By intercrossing \"weaver\" with NGL mice (dual GFP/luciferase-NF-\u03ba\u0392 reporter mice, NF-\u03ba\u0392.GFP.Luc), we obtained Weaver/NGL mice that express the NF-\u03baB reporter in all somatic cells. Acute BNN-20 administration to Weaver/NGL mice induced a strong NF-\u03baB-dependent transcriptional response in the brain as detected by bioluminescence imaging, which was abolished by co-administration of the TrkB inhibitor ANA-12. This indicates that BNN-20 exerts its beneficial action (at least in part) through the TrkB-PI3K-Akt-NF-\u03baB signaling pathway. These results could be of clinical relevance, as they suggest BNN-20 as an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway, mimicking the action of the endogenous neurotrophin BDNF. Thus BNN-20 could be proposed for treatment of PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28461162", "endSection": "abstract" } ] }, { "body": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24150941", "http://www.ncbi.nlm.nih.gov/pubmed/19922872" ], "ideal_answer": [ "The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail", "The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated", "MOZ/MYST3 complex associates with histone H3 with high affinity and specificity. Both proteins share a PHD finger domain.", "The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification.", "In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries. The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification", "MOZ/MYST3 complex associates with histone H3 with PHD finger domain.", "ere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A.", "ere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated", "In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries. The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification ere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A." ], "exact_answer": [ "the double PHD finger domain" ], "type": "factoid", "id": "5d38663da1e1595105000001", "snippets": [ { "offsetInBeginSection": 844, "offsetInEndSection": 1020, "text": "In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19922872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The double PHD finger domain of MOZ/MYST3 induces \u03b1-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24150941", "endSection": "title" }, { "offsetInBeginSection": 130, "offsetInEndSection": 467, "text": "ere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24150941", "endSection": "abstract" } ] }, { "body": "Which company sells the drug Afrezza since 2015?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26222134" ], "ideal_answer": [ "Afrezza has been marketed by Sanofi since February 2015." ], "exact_answer": [ "Sanofi" ], "type": "factoid", "id": "5e776db8835f4e4777000011", "snippets": [ { "offsetInBeginSection": 635, "offsetInEndSection": 909, "text": "In contrary, MannKind Corporation started developing its ultra-rapid-acting insulin Afrezza in a bold bid, probably by managing the issues in which Exubera was not successful. Afrezza has been marketed since February, 2015 by Sanofi after getting FDA approval in June 2014. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222134", "endSection": "abstract" } ] }, { "body": "Is there a role for MRPL53 in cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29053389" ], "ideal_answer": [ "No. MRPL53 is a new candidate gene for orofacial clefting identified using an eQTL approach." ], "exact_answer": "no", "type": "yesno", "id": "5e35d3c6158f994d3a000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29053389", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1461, "text": "A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29053389", "endSection": "abstract" } ] }, { "body": "Does Uc.63+ promote sensitivity to treatment in prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29212226" ], "ideal_answer": [ "No. Overexpression of Uc.63+ increases the expression of AR and its downstream molecule PSA and promotes resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients is higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis indicates that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020).", "No. Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. Moreover, high expression of serum Uc63+ correlated with a worse prognosis (P = 0.020) in patients treated with copropane versus placebo.", "No. Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. In contrast, Uc-63+ enhances sensitivity to treatment in other types of prostate cancer" ], "exact_answer": "no", "type": "yesno", "id": "5e36a4b7b5b409ea53000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 1758, "text": "The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC. Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020). These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "title" }, { "offsetInBeginSection": 1529, "offsetInEndSection": 1774, "text": "These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1224, "text": "Furthermore , overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 1512, "offsetInEndSection": 1759, "text": "These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1211, "text": "Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" }, { "offsetInBeginSection": 1512, "offsetInEndSection": 1758, "text": "These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212226", "endSection": "abstract" } ] }, { "body": "What is the gene PTENP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27936183" ], "ideal_answer": [ "PTEN pseudogene (PTENp) acts as an endogenous RNA, which regulates its parental gene by competitively binding to the 3' UTR of PTEN gene in the human." ], "exact_answer": [ "PTEN pseudogene (PTENp) acts as an endogenous RNA, which regulates its parental gene by competitively binding to the 3' UTR of PTEN gene in the human." ], "type": "factoid", "id": "5e6df7887fc1ee872b000001", "snippets": [ { "offsetInBeginSection": 66, "offsetInEndSection": 326, "text": "PTEN pseudogene (PTENp) acts as an endogenous RNA, which regulates its parental gene by competitively binding to the 3' UTR of PTEN gene in the human. Despite the importance of this pseudogene, little is known about the molecular evolution of PTENp in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27936183", "endSection": "abstract" } ] }, { "body": "Rachmilewitz Index is used for which diseases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30130840", "http://www.ncbi.nlm.nih.gov/pubmed/25823689", "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "http://www.ncbi.nlm.nih.gov/pubmed/15603341", "http://www.ncbi.nlm.nih.gov/pubmed/26894632", "http://www.ncbi.nlm.nih.gov/pubmed/7752802", "http://www.ncbi.nlm.nih.gov/pubmed/23511035", "http://www.ncbi.nlm.nih.gov/pubmed/8649955", "http://www.ncbi.nlm.nih.gov/pubmed/19462421", "http://www.ncbi.nlm.nih.gov/pubmed/30353757", "http://www.ncbi.nlm.nih.gov/pubmed/26985865", "http://www.ncbi.nlm.nih.gov/pubmed/24981894", "http://www.ncbi.nlm.nih.gov/pubmed/19821197", "http://www.ncbi.nlm.nih.gov/pubmed/26642816", "http://www.ncbi.nlm.nih.gov/pubmed/24742079", "http://www.ncbi.nlm.nih.gov/pubmed/17168120" ], "ideal_answer": [ "Rachmilewitz Index is used for assessment of endoscopic disease activity of patients with ulcerative colitis." ], "exact_answer": [ "ulcerative colitis" ], "type": "factoid", "id": "5e47546d3f54159529000019", "snippets": [ { "offsetInBeginSection": 511, "offsetInEndSection": 929, "text": "At present, many endoscopic indices of ulcerative colitis have been introduced, including the Truelove and Witts Endoscopy Index, Baron Index, Powell-Tuck Index, Sutherland Index, Mayo Clinic Endoscopic Sub-Score, Rachmilewitz Index, Modified Baron Index, Endoscopic Activity Index, Ulcerative Colitis Endoscopic Index of Severity, Ulcerative Colitis Colonoscopic Index of Severity, and Modified Mayo Endoscopic Score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30130840", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 909, "text": "MATERIALS AND METHODS: Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan-Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30353757", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1628, "text": "RESULTS AND CONCLUSION: A high correlation was demonstrated between three of the 11 evaluated clinical indices - Improvement Based on Individual Symptom Scores, Ulcerative Colitis Disease Activity Index, and Schroeder Index - and all nine endoscopic indices - Ulcerative Colitis Endoscopic Index of Severity, Baron Score, Schroeder Index, Feagan Index, Powell-Tuck Index, Rachmilewitz Index, Sutherland Index, Lofberg Index, and Lemman Index. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26894632", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 575, "text": "A prospective open-label, single-center study was performed in 10 patients with active UC (Rachmilewitz Clinical Activity Index [CAI]\u2009\u2265\u20098 points; Rachmilewitz Endoscopic Index\u2009\u2265\u20097 points). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24981894", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 867, "text": "METHODS: Thirty patients with mild to moderate IBD (Crohn's Disease Activity Index (CDAI) <220 or Rachmilewitz Index (RI) <11) were randomized 1:1 to either supervised moderate-intensity running thrice a week for 10 weeks or a control group who were not prescribed any exercise. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25823689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "BACKGROUND: To investigate whether anxiety and depression levels are associated with Heat Shock Protein 70 (HSP70) induction in the colon of patients with ulcerative colitis (UC).METHODS: The design was cross-sectional. Clinical activity was assessed by the Rachmilewitz Index (CAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24742079", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 838, "text": "Endoscopic disease activities were scored independently according to the Simple Endoscopic Score for CD in patients with CD and to the Rachmilewitz Index in patients with UC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23511035", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 759, "text": "The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "OBJECTIVE\n\nThe aim of this study was to assess the concordance between the Rachmilewitz endoscopic activity index (EAI) and the Harpaz histopathological activity scoring system (HSS), which are used for evaluating the disease activity of ulcerative colitis (UC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26985865", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 760, "text": "The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "endSection": "abstract" }, { "offsetInBeginSection": 1333, "offsetInEndSection": 1463, "text": "Disease activity was described according to Rachmilewitz scale in UC and in CD according to Crohn's disease activity index (CDAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15603341", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1377, "text": "RESULTS\n\nFollowing 12 months, allogeneic bone marrow (BM) MSC transplantation performed thrice during a month caused the greatest reduction in the Rachmilewitz clinical activity index, Mayo endoscopic activity index, and Gebs pathohistological index in patients with UC as compared to those who had underwent one transplantation or received 5-ASA preparations and GCS (p < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19462421", "endSection": "title" }, { "offsetInBeginSection": 341, "offsetInEndSection": 507, "text": "METHODS\n\nUC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19462421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "BACKGROUND\n\nThe accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis (UC) according the Rachmilewitz Score is so far unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19462421", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1016, "text": "Clinical activity in Chron's disease was measured by Crohn disease activity index and in ulcerative colitis patients by Rachmilewitz endoscopic index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19821197", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 757, "text": "The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1458, "text": "Disease activity was described according to Rachmilewitz scale in UC and in CD according to Crohn's disease activity index (CDAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15603341", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 501, "text": "Rachmilewitz scoring system (endoscopic activity index [EAI]) was used to determine UC activity, and as for CD activity, CD activity index (CDAI) scoring was used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26642816", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 504, "text": "METHODS UC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19462421", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 421, "text": "The Rachmilewitz scale is better in distinguishing between UC and CNS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8649955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "The aim of this study was to assess the concordance between the Rachmilewitz endoscopic activity index ( EAI ) and the Harpaz histopathological activity scoring system ( HSS) , which are used for evaluating the disease activity of ulcerative colitis ( UC ) .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26985865", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1061, "text": "In patients with ulcerative colitis suffering from arthritis a significant increase of disease activity ( Rachmilewitz index ) could be shown as compared to ulcerative colitis patients without arthritis ( p < 0.02) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7752802", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 760, "text": "The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1377, "text": "RESULTS\nFollowing 12 months, allogeneic bone marrow (BM) MSC transplantation performed thrice during a month caused the greatest reduction in the Rachmilewitz clinical activity index, Mayo endoscopic activity index, and Gebs pathohistological index in patients with UC as compared to those who had underwent one transplantation or received 5-ASA preparations and GCS (p < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1463, "text": "Disease activity was described according to Rachmilewitz scale in UC and in CD according to Crohn's disease activity index (CDAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15603341", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 840, "text": "Endoscopic disease activities were scored independently according to the Simple Endoscopic Score for CD in patients with CD and to the Rachmilewitz Index in patients with UC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23511035", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 758, "text": "The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22994082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "BACKGROUND: The accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis (UC) according the Rachmilewitz Score is so far unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19462421", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 505, "text": "METHODS: UC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19462421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "OBJECTIVE: The aim of this study was to assess the concordance between the Rachmilewitz endoscopic activity index (EAI) and the Harpaz histopathological activity scoring system (HSS), which are used for evaluating the disease activity of ulcerative colitis (UC).SUBJECTS AND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26985865", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 502, "text": "Rachmilewitz scoring system (endoscopic activity index [EAI]) was used to determine UC activity, and as for CD activity, CD activity index (CDAI) scoring was used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26642816", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 474, "text": "Rachmilewitz scoring system (endoscopic activity index [EAI]) was used to determine UC activity, and as for CD activity, CD activity index (CDAI) scoring was used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26642816", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 758, "text": "Crohn's disease activity index and the Rachmilewitz endoscopic activity index for ulcerative colitis were used to assess disease activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17168120", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1416, "text": "Disease activity was described according to Rachmilewitz scale in UC and in CD according to Crohn's disease activity index (CDAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15603341", "endSection": "abstract" } ] }, { "body": "List angiotensin-converting-enzyme inhibitors.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27100959", "http://www.ncbi.nlm.nih.gov/pubmed/28475676" ], "ideal_answer": [ "captopril\nenalapril\nlisinopril\nramipril" ], "type": "summary", "id": "5e80669e835f4e4777000025", "snippets": [ { "offsetInBeginSection": 119, "offsetInEndSection": 168, "text": "angiotensin-converting enzyme inhibitor captopril", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27100959", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 339, "text": "enalapril, lisinopril, or ramipril ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28475676", "endSection": "abstract" } ] }, { "body": "How does androgen deprivation therapy affect pain perception?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28941963" ], "ideal_answer": [ "There were no significant changes in pain thresholds, ratings, or other response to quantitative sensory tests over the 6-month course of the study. Clinical pain did not differ between test and control groups, and no changes from baseline were observed in their group." ], "type": "summary", "id": "5e774660835f4e4777000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Effects of Androgen Deprivation Therapy on Pain Perception, Quality of Life, and Depression in Men With Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941963", "endSection": "title" }, { "offsetInBeginSection": 1294, "offsetInEndSection": 1557, "text": "There were no significant changes in pain thresholds, ratings, or other responses to quantitative sensory tests over the 6-month course of the study. Clinical pain did not differ between the two groups, and no changes from baseline were observed in either group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941963", "endSection": "abstract" }, { "offsetInBeginSection": 1755, "offsetInEndSection": 1905, "text": "ADT in men with PCa is associated with worsening of depression scores and QOL but is not associated with changes in clinical pain or pain sensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941963", "endSection": "abstract" } ] }, { "body": "What is OAC CHV?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "http://www.ncbi.nlm.nih.gov/pubmed/27884812" ], "ideal_answer": [ "The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), which contains health-related terms used by lay consumers,", "The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), contains health-related terms used by lay consumers." ], "exact_answer": [ "Layman's term vocabulary for health related terms" ], "type": "factoid", "id": "5e3ab4f8b5b409ea5300001b", "snippets": [ { "offsetInBeginSection": 1234, "offsetInEndSection": 1296, "text": "Open-Access Collaborative Consumer Health Vocabulary (OAC CHV)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27884812", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 311, "text": "The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), which contains health-related terms used by lay consumers, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 349, "text": "The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), which contains health-related terms used by lay consumers, has been created to bridge such a gap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 550, "text": "Specifically, the OAC CHV facilitates consumers' health information retrieval by enabling consumer-facing health applications to translate between professional language and consumer friendly language.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 352, "text": "The Open Access and Collaborative Consumer Health Vocabulary ( OAC CHV) , which contains health-related terms used by lay consumers , has been created to bridge such a gap", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 555, "text": "Specifically , the OAC CHV facilitates consumers' health information retrieval by enabling consumer-facing health applications to translate between professional language and consumer friendly language", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 551, "text": "Specifically, the OAC CHV facilitates consumers' health information retrieval by enabling consumer-facing health applications to translate between professional language and consumer friendly language.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 350, "text": "The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), which contains health-related terms used by lay consumers, has been created to bridge such a gap.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28359728", "endSection": "abstract" } ] }, { "body": "What is known about autosomal dominant Alzheimer\u2019s disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28949931", "http://www.ncbi.nlm.nih.gov/pubmed/29182052" ], "ideal_answer": [ "The first autosomal dominant mutation in the amyloid precursor protein (APP) gene was described in 1991. Later, AD was also associated with mutated early-onset (presenilin 1/2, PSEN1/2 and APP) and late-onset (apolipoprotein E, ApoE) genes. Genome-wide association and linkage analysis studies with identified multiple genomic areas have implications for the treatment of AD.\nThe Dominantly Inherited Alzheimer Network, an international family-clustered registry to study autosomal dominant Alzheimer disease which is a rare form of Alzheimer disease caused by mutations in any of the three genes including the amyloid precursor protein, presenilin 1 and presenilin 2." ], "type": "summary", "id": "5e6e767e51b80c9423000006", "snippets": [ { "offsetInBeginSection": 539, "offsetInEndSection": 915, "text": "The first autosomal dominant mutation in the amyloid precursor protein (APP) gene was described in 1991. Later, AD was also associated with mutated early-onset (presenilin 1/2, PSEN1/2 and APP) and late-onset (apolipoprotein E, ApoE) genes. Genome-wide association and linkage analysis studies with identified multiple genomic areas have implications for the treatment of AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28949931", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1584, "text": "we apply the proposed methodology to the data of several biomarkers collected by the Dominantly Inherited Alzheimer Network, an international family-clustered registry to study autosomal dominant Alzheimer disease which is a rare form of Alzheimer disease caused by mutations in any of the three genes including the amyloid precursor protein, presenilin 1 and presenilin 2. We estimate the accuracy of several cerebrospinal fluid and neuroimaging biomarkers in differentiating three diagnostic and genetic populations: normal non-mutation carriers, asymptomatic mutation carriers, and symptomatic mutation carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29182052", "endSection": "abstract" } ] }, { "body": "List characteristic features of the Revesz syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29749240", "http://www.ncbi.nlm.nih.gov/pubmed/17901676", "http://www.ncbi.nlm.nih.gov/pubmed/17990901", "http://www.ncbi.nlm.nih.gov/pubmed/24321428", "http://www.ncbi.nlm.nih.gov/pubmed/27065378", "http://www.ncbi.nlm.nih.gov/pubmed/25067791", "http://www.ncbi.nlm.nih.gov/pubmed/17874088", "http://www.ncbi.nlm.nih.gov/pubmed/28866069", "http://www.ncbi.nlm.nih.gov/pubmed/28095086" ], "ideal_answer": [ "Revesz syndrome is characterized by retinopathy, aplastic anemia, nail dystrophy, and cerebellar hypoplasia." ], "exact_answer": [ [ "retinopathy" ], [ "aplastic anemia" ], [ "nail dystrophy" ], [ "cerebellar hypoplasia" ] ], "type": "list", "id": "5e4609b83f54159529000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "PURPOSES: To inform about a case of Revesz syndrome (RS) with initial ophthalmological symptomatology of severe proliferative vitreoretinopathy of the left eye (LE). After the aplastic anemia had developed, RS was established. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749240", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1125, "text": "In preoperative screening,\u00a0thrombocytopenia was detected; later, severe pancytopenia developed. Considering the hematological findings and clinical appearance, we suspected RS, which was confirmed by genetic tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749240", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1689, "text": "CONCLUSIONS: RS is an extremely rare condition.\u00a0 The initial symptomatology could be ophthalmological or hematological.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749240", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 822, "text": "The patient was found to have a TINF2 mutation consistent with a diagnosis of Revesz syndrome, a variant of dyskeratosis congenita. He underwent successful bone marrow transplantation, and on subsequent evaluation was found to have retinal hemorrhages, vessel sclerosis, and cotton wool spots in the right eye associated with peripheral retinal nonperfusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28866069", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 481, "text": "These \"telomeropathies\" also include Hoyeraal-Hreidarsson syndrome (HH) and Revesz syndrome, which are severe forms of dyskeratosis congenita, as well as a subset of idiopathic pulmonary fibrosis, aplastic anemia, and Coats' plus syndrome. Retinopathy has only rarely been reported in DC and HH, but is universally present in Coats' plus and Revesz syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27065378", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 397, "text": "Revesz syndrome, a subtype of dyskeratosis congenita (DC) caused by TINF2 mutation, combines marrow failure with exudative retinopathy, intracranial calcifications, and neurocognitive impairment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25067791", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 211, "text": "Revesz\u00a0syndrome, a variant disorder, is characterized by retinopathy, aplastic anemia, nail dystrophy, and cerebellar hypoplasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "A 5-year-old girl was admitted with pallor, hypopigmented sparse hair, tongue ulcers, atrophic nail changes, hypoplastic anemia and bilateral exudative retinopathy. A diagnosis of Revesz syndrome was made. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17901676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Revesz syndrome is a variant of dyskeratosis congenita characterized by aplastic anemia, retinopathy, and central nervous system abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17874088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "BACKGROUND\n\nRevesz syndrome is a telomere disorder in the dyskeratosis congenita (DKC) spectrum characterized by exudative retinopathy, bone marrow failure, neuroradiographic abnormalities, and integumentary findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28095086", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 210, "text": "Revesz syndrome, a variant disorder, is characterized by retinopathy, aplastic anemia, nail dystrophy, and cerebellar hypoplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Revesz syndrome is a variant of dyskeratosis congenita characterized by aplastic anemia, retinopathy, and central nervous system abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17874088", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 210, "text": "Revesz\u00a0syndrome, a variant disorder, is characterized by retinopathy, aplastic anemia, nail dystrophy, and cerebellar hypoplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321428", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 409, "text": "Revesz syndrome , a subtype of dyskeratosis congenita ( DC ) caused by TINF2 mutation , combines marrow failure with exudative retinopathy , intracranial calcifications , and neurocognitive impairment . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25067791", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Revesz syndrome is a telomere disorder in the dyskeratosis congenita ( DKC ) spectrum characterized by exudative retinopathy , bone marrow failure , neuroradiographic abnormalities , and integumentary findings .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28095086", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 218, "text": "Revesz\u00a0syndrome , a variant disorder , is characterized by retinopathy , aplastic anemia , nail dystrophy , and cerebellar hypoplasia . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24321428", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 671, "text": "The findings of myelofibrosis , retinopathy , and cerebral calcifications indicate that this could be a case of a rare condition known as Revesz syndrome .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17990901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "To inform about a case of Revesz syndrome ( RS ) with initial ophthalmological symptomatology of severe proliferative vitreoretinopathy of the left eye ( LE) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "BACKGROUND\nRevesz syndrome is a telomere disorder in the dyskeratosis congenita (DKC) spectrum characterized by exudative retinopathy, bone marrow failure, neuroradiographic abnormalities, and integumentary findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28095086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND: Revesz syndrome is a telomere disorder in the dyskeratosis congenita (DKC) spectrum characterized by exudative retinopathy, bone marrow failure, neuroradiographic abnormalities, and integumentary findings.MATERIALS/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28095086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Revesz syndrome is a telomere disorder in the dyskeratosis congenita (DKC) spectrum characterized by exudative retinopathy, bone marrow failure, neuroradiographic abnormalities, and integumentary findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28095086", "endSection": "abstract" } ] }, { "body": "Does BNN27 promote memory loss?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28274826" ], "ideal_answer": [ "No. The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats." ], "exact_answer": "no", "type": "yesno", "id": "5e2b3d97fbd6abf43b00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28274826", "endSection": "title" }, { "offsetInBeginSection": 156, "offsetInEndSection": 1160, "text": "BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28274826", "endSection": "abstract" } ] }, { "body": "Are genomic regulatory blocks (GRBs) any different than TADs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28874668" ], "ideal_answer": [ "No, clusters of CNEs (GRBs) strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation. The close correspondence between extreme noncoding conservation and TADs suggests that these TADs are ancient, revealing a regulatory architecture conserved over hundreds of millions of years." ], "exact_answer": "no", "type": "yesno", "id": "5e4946bf6d0a277941000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "title" }, { "offsetInBeginSection": 235, "offsetInEndSection": 1358, "text": "Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs). Their function and distribution around important regulatory genes raises the question of how they relate to 3D conformation of these loci. Here, we show that clusters of CNEs strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation. The close correspondence between extreme noncoding conservation and TADs suggests that these TADs are ancient, revealing a regulatory architecture conserved over hundreds of millions of years.Metazoan genomes contain many clusters of conserved noncoding elements. Here, the authors provide evidence that these clusters coincide with distinct topologically associating domains in humans and Drosophila, revealing a conserved regulatory genomic architecture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874668", "endSection": "abstract" } ] }, { "body": "Are Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumors(MPNST) rare in neurofibromatosis patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27593814", "http://www.ncbi.nlm.nih.gov/pubmed/24926928" ], "ideal_answer": [ "Spinal intradural primary malignant peripheral nerve sheath tumors (MPNST) are rare in patients without neurofibromatosis.", "No, Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumors(MPNST) rare in patients without neurofibromatosis.", "yes, Primary malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare in patients without a history of neurofibromatosis; only 18 cases have been reported in the English-language literature to this point." ], "exact_answer": "no", "type": "yesno", "id": "5e67bc121af46fc13000001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Spinal intradural primary malignant peripheral nerve sheath tumors (MPNST) are rare in patients without neurofibromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27593814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Primary malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare in patients without a history of neurofibromatosis; only 18 cases have been reported in the English-language literature to this point.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24926928", "endSection": "abstract" } ] }, { "body": "What does MVA85A stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22789508" ], "ideal_answer": [ "MVA85A is the Modified Vaccinia virus Ankara expressing Antigen 85A." ], "exact_answer": [ "Modified Vaccinia virus Ankara expressing Antigen 85A" ], "type": "factoid", "id": "5e776845835f4e477700000a", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 320, "text": "A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22789508", "endSection": "abstract" } ] }, { "body": "Can MVA85A confer immunity against smallpox?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25726088" ], "ideal_answer": [ "No MVA85A is a candidate tuberculosis vaccine." ], "exact_answer": "no", "type": "yesno", "id": "5e776541835f4e4777000009", "snippets": [ { "offsetInBeginSection": 142, "offsetInEndSection": 326, "text": "We assessed the safety, immunogenicity, and efficacy of a candidate tuberculosis vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in adults infected with HIV-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25726088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25726088", "endSection": "title" } ] }, { "body": "Is MLL3 part of the ASCOM complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21330447" ], "ideal_answer": [ "Yes" ], "exact_answer": "yes", "type": "yesno", "id": "5e6e2c1e7fc1ee872b000002", "snippets": [ { "offsetInBeginSection": 31, "offsetInEndSection": 60, "text": "MLL3 as part of ASCOM complex", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330447", "endSection": "title" }, { "offsetInBeginSection": 680, "offsetInEndSection": 756, "text": "MLL3 as part of activating signal cointegrator-2 -containing complex (ASCOM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330447", "endSection": "abstract" } ] }, { "body": "What are the effects of CAMK4 inhibition?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24667640", "http://www.ncbi.nlm.nih.gov/pubmed/24839356", "http://www.ncbi.nlm.nih.gov/pubmed/30462889" ], "ideal_answer": [ " Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation. Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator a (CREM-a) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation. CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling", "CaMK4 inhibition has potential as a therapeutic strategy for Th17-driven autoimmune diseases.", "CaMK4-dependent activation of AKT/mTOR and CREM-a underlies autoimmunity-associated Th17 imbalance Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation. Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator a (CREM-a) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation.", "Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator a (CREM-a) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation." ], "exact_answer": [ [ "Th17 differentiation" ], [ "reduction of Il17 expression" ], [ "decreased activation of cAMP" ] ], "type": "list", "id": "5d387360a1e1595105000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "CaMK4-dependent activation of AKT/mTOR and CREM-\u03b1 underlies autoimmunity-associated Th17 imbalance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667640", "endSection": "title" }, { "offsetInBeginSection": 223, "offsetInEndSection": 373, "text": " Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667640", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1015, "text": "Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator \u03b1 (CREM-\u03b1) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667640", "endSection": "abstract" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1309, "text": "CaMK4 inhibition has potential as a therapeutic strategy for Th17-driven autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24667640", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1038, "text": "CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24839356", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1200, "text": "CaMK4 inhibition significantly decreased the levels of glycolytic intermediates such as glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate, whereas it did not affect the levels of the pentose phosphate pathway intermediates such as 6-Phospho-D-gluconate, ribulose-5-phosphate, ribose-5-phosphate and phosphoribosyl pyrophosphate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30462889", "endSection": "abstract" } ] }, { "body": "List cohesinopathies", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25352100", "http://www.ncbi.nlm.nih.gov/pubmed/28422453" ], "ideal_answer": [ "Roberts syndrome (RBS), Cornelia de Lange Syndrome (CdLS), Warsaw Breakage Syndrome (WABS) and Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome." ], "exact_answer": [ [ "Roberts syndrome", "RBS" ], [ "Cornelia de Lange Syndrome", "CdLS" ], [ "Warsaw Breakage Syndrome", "WABS" ], [ "Chronic Atrial and Intestinal Dysrhythmia syndrome", "CAID" ] ], "type": "list", "id": "5e4949d36d0a277941000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1081, "text": "Genetic mapping studies reveal that mutations in cohesion pathways are responsible for multispectrum developmental abnormalities termed cohesinopathies. These include Roberts syndrome (RBS), Cornelia de Lange Syndrome (CdLS), and Warsaw Breakage Syndrome (WABS). The cohesinopathies are characterized by overlapping phenotypes ranging from craniofacial deformities, limb defects, and mental retardation. Though these syndromes share a similar suite of phenotypes and arise due to mutations in a common cohesion pathway, the underlying mechanisms are currently believed to be distinct. Defects in mitotic failure and apoptosis i.e. trans DNA tethering events are believed to be the underlying cause of RBS, whereas the underlying cause of CdLS is largely modeled as occurring through defects in transcriptional processes i.e. cis DNA tethering events. Here, we review recent findings described primarily in zebrafish, paired with additional studies in other model systems, including human patient cells, which challenge the notion that cohesinopathies represent separate syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28422453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "A new study identifies homozygous missense mutations in SGOL1, which encodes a component of the cohesin complex, in a newly described disorder termed Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome. These findings implicate cohesin in the regulation of intrinsic cardiac and intestinal rhythm and further expand the growing group of disorders termed the cohesinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25352100", "endSection": "abstract" } ] }, { "body": "Which protein is mutated in Erythropoietic Protoporphyria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29610169", "http://www.ncbi.nlm.nih.gov/pubmed/30175727", "http://www.ncbi.nlm.nih.gov/pubmed/29116687" ], "ideal_answer": [ "Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients." ], "exact_answer": [ "FECH gene, ferrochelatase" ], "type": "factoid", "id": "5e822615835f4e4777000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29116687", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 270, "text": " Erythropoietic protoporphyria (EPP) is the most common inherited porphyria in children and is diagnosed in most individuals after the onset of cutaneous manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29610169", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 107, "text": " an erythropoietic protoporphyria (EPP)-associated ferrochelatase (FECH) mutation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30175727", "endSection": "abstract" } ] }, { "body": "Is marimastat effective for small-cell lung cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11894017", "http://www.ncbi.nlm.nih.gov/pubmed/12757409", "http://www.ncbi.nlm.nih.gov/pubmed/12431965" ], "ideal_answer": [ "No. Marimastat is not effective for small-cell lung cancer." ], "exact_answer": "no", "type": "yesno", "id": "5e476da1d14c9f295d000002", "snippets": [ { "offsetInBeginSection": 1961, "offsetInEndSection": 2221, "text": "The phase III trial in small cell lung cancer was discontinued when the results of study 140 were released in February 2001 showing that marimastat was not significantly more effective than placebo in prolonging the survival of small cell lung cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757409", "endSection": "abstract" }, { "offsetInBeginSection": 1643, "offsetInEndSection": 1795, "text": "CONCLUSION: Treatment with marimastat after induction therapy for SCLC did not result in improved survival and had a negative impact on quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12431965", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1102, "text": "There were no significant differences in survival in a non-small cell lung cancer prinomastat study, and in a small cell lung cancer marimastat trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11894017", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1120, "text": "There were no significant differences in survival in a non-small cell lung cancer prinomastat study , and in a small cell lung cancer marimastat trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11894017", "endSection": "abstract" }, { "offsetInBeginSection": 1961, "offsetInEndSection": 2222, "text": "The phase III trial in small cell lung cancer was discontinued when the results of study 140 were released in February 2001 showing that marimastat was not significantly more effective than placebo in prolonging the survival of small cell lung cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12757409", "endSection": "abstract" } ] }, { "body": "Which part of the TNFR2 gene is genetically associated with Systemic Lupus Erythematosus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11197692", "http://www.ncbi.nlm.nih.gov/pubmed/11607787", "http://www.ncbi.nlm.nih.gov/pubmed/11169260", "http://www.ncbi.nlm.nih.gov/pubmed/10395102", "http://www.ncbi.nlm.nih.gov/pubmed/11196716" ], "ideal_answer": [ "There is a TNFR2 3' flanking region polymorphism in systemic lupus erythematosus.", "A TNFR2 3' flanking region polymorphism in systemic lupus erythematosus.", "A tnfr2 3' flanking region polymorphism in systemic lupus erythematosus has been shown to be significantly associated with selenocytoplasmic lupus erythematotosus. No transmission distortion was observed for tnpr2-196r allele." ], "exact_answer": [ "3' flanking region" ], "type": "factoid", "id": "5d386ed6a1e1595105000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "A TNFR2 3' flanking region polymorphism in systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11196716", "endSection": "title" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1027, "text": "We therefore characterized the frequency of a genetic polymorphism in the 3' untranslated region of the TNFR2 gene in Caucasoid SLE patients and geographically matched controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11196716", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1686, "text": " In conclusion, the TNFR2 196R allele was found to be significantly associated with the susceptibility to SLE in the Japanese population. Further population and functional studies will be of particular importance to establish TNFR2 as one of the susceptibility genes to SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10395102", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 857, "text": "Thus, among the non-synonymous cSNPs, only nt587 (T-->G) (M196R) was found to be significantly associated with SLE in Japanese.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11197692", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1054, "text": "No transmission distortion was observed for TNFR2-196R allele. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11607787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Lack of association between the Met196Arg polymorphism in the TNFR2 gene and autoimmune diseases accompanied by vasculitis including SLE in Japanese.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11169260", "endSection": "title" } ] }, { "body": "What is VISMapper?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28931371" ], "ideal_answer": [ "VISMapper is a vector integration site analysis web server to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org.", "The possibility of integrating viral vectors to become a persistent part of the host genome makes them a crucial element of clinical gene therapy. However, viral integration has associated risks, such as the unintentional activation of oncogenes that can result in cancer. Therefore, the analysis of integration sites of retroviral vectors is a crucial step in developing safer vectors for therapeutic use. VISMapper is a vector integration site analysis web server to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org." ], "type": "summary", "id": "5e51de866d0a27794100003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "VISMapper: ultra-fast exhaustive cartography of viral insertion sites for gene therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931371", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 872, "text": "The possibility of integrating viral vectors to become a persistent part of the host genome makes them a crucial element of clinical gene therapy. However, viral integration has associated risks, such as the unintentional activation of oncogenes that can result in cancer. Therefore, the analysis of integration sites of retroviral vectors is a crucial step in developing safer vectors for therapeutic use.RESULTS: Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org .CONCLUSIONS: Because it uses novel mapping algorithms VISMapper is remarkably faster than previous available programs. It also provides a useful graphical interface to analyze the integration sites found in the genomic context.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931371", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 586, "text": "RESULTS\n\nHere we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931371", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 583, "text": "RESULTS Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931371", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 586, "text": "RESULTS\nHere we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931371", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 584, "text": "RESULTS: Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931371", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 564, "text": "Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931371", "endSection": "abstract" } ] }, { "body": "What is Taupathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23745112", "http://www.ncbi.nlm.nih.gov/pubmed/26611895" ], "ideal_answer": [ "Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau protein.", "Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau", "Taupathy is a progressive neurodegenerative disease of the central nervous system caused by autosomal recessive mutations in the Tau (amyloid precursor protein 1) gene.", "Taupathy is an autosomal-dominant neurodegenerative disease characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and is characterized by loss of motor, sensory, and sensory function." ], "type": "summary", "id": "5e3c83c548dab47f26000001", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 129, "text": "Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26611895", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 349, "text": "CTE is defined as a tauopathy with a distribution of tau-positive neurofibrillary tangles (NFTs) that is distinct from other tauopathies,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23745112", "endSection": "abstract" } ] }, { "body": "Is Figitumumab effective for non-small cell lung cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28104361", "http://www.ncbi.nlm.nih.gov/pubmed/20676809", "http://www.ncbi.nlm.nih.gov/pubmed/24888810", "http://www.ncbi.nlm.nih.gov/pubmed/23826179", "http://www.ncbi.nlm.nih.gov/pubmed/21907495", "http://www.ncbi.nlm.nih.gov/pubmed/21102589", "http://www.ncbi.nlm.nih.gov/pubmed/21717907" ], "ideal_answer": [ "No. Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R) antibody figitumumab in non-small cell lung cancer (NSCLC) patients have been discontinued owing to lack of survival benefit. Adding figitumumab to standard chemotherapy also failed to increase overall survival in patients with advanced nonadenocarcinoma NSCLC." ], "exact_answer": "no", "type": "yesno", "id": "5e4b64126d0a277941000028", "snippets": [ { "offsetInBeginSection": 119, "offsetInEndSection": 270, "text": "A phase III study failed for carboplatin, paclitaxel, with or without figitumumab in first-line treating metastatic non-small cell lung cancer (NSCLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28104361", "endSection": "abstract" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1650, "text": "CONCLUSION: Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24888810", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1352, "text": "Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24888810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R) antibody figitumumab in non-small cell lung cancer (NSCLC) patients have been discontinued owing to lack of survival benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23826179", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 1085, "text": "Two phase III trials of the anti-IGF-1R monoclonal antibody, figitumumab (CP-751,871), were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints. In light of disappointing clinical data with figitumumab and other targeted agents, it is likely that the use of molecular markers will become important in predicting response to treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21907495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Phase III trials of the anti-insulin-like growth factor-1 receptor ( IGF1R ) antibody figitumumab in non-small cell lung cancer ( NSCLC ) patients have been discontinued owing to lack of survival benefit . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23826179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Phase III trials of the anti-insulin-like growth factor type 1 receptor ( IGF-IR ) antibody figitumumab ( F ) in unselected non-small-cell lung cancer ( NSCLC ) patients were recently discontinued owing to futility . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21102589", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 367, "text": "One recent phase III trial of the IGF-1R inhibitor figitumumab in patients with non-small-cell lung cancer was discontinued after an interim analysis showed no survival improvement . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21717907", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 544, "text": "The insulin-like growth factor receptor ( IGF-1R ) monoclonal antibody figitumumab , while initially promising , appears to increase toxicity and death in combination with chemotherapy in the treatment of patients with NSCLC of squamous histology; therefore , clinical development of this class of agents will need to proceed with caution . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20676809", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 921, "text": "Two phase III trials of the anti-IGF-1R monoclonal antibody , figitumumab ( CP-751,871) , were discontinued in 2010 as it was considered unlikely either trial would meet their primary endpoints . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21907495", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 278, "text": "A phase III study failed for carboplatin , paclitaxel , with or without figitumumab in first-line treating metastatic non-small cell lung cancer ( NSCLC) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28104361", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1351, "text": "Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24888810", "endSection": "abstract" } ] }, { "body": "The LINCS L1000 data set contains gene expression data for drug treated human cells, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27153606", "http://www.ncbi.nlm.nih.gov/pubmed/29745839", "http://www.ncbi.nlm.nih.gov/pubmed/28413689", "http://www.ncbi.nlm.nih.gov/pubmed/31258549", "http://www.ncbi.nlm.nih.gov/pubmed/27796074", "http://www.ncbi.nlm.nih.gov/pubmed/25609570" ], "ideal_answer": [ "The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset measures changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs.", "yes, The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big data provide gene expression profiles induced by over 10 000 compounds, shRNAs, and kinase inhibitors using the L1000 platform.", "TheLINCS L1000 data set contains gene expression data for drug treated human cells, yes" ], "exact_answer": "yes", "type": "yesno", "id": "5e3ab58db5b409ea5300001c", "snippets": [ { "offsetInBeginSection": 316, "offsetInEndSection": 548, "text": " Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27153606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big data provide gene expression profiles induced by over 10\u2009000 compounds, shRNAs, and kinase inhibitors using the L1000 platform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25609570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27796074", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 293, "text": " Recently, resources such as the Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 database provide gene expression profiles induced by various chemical and genetic perturbations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29745839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The library of integrated network-based cellular signatures (LINCS) L1000 data set currently comprises of over a million gene expression profiles of chemically perturbed human cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28413689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The LINCS L1000 data repository contains almost two million gene expression profiles for thousands of small molecules and drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31258549", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 548, "text": "The GE data is from the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27153606", "endSection": "abstract" } ] }, { "body": "What is a cytokine storm?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24728596", "http://www.ncbi.nlm.nih.gov/pubmed/20736486", "http://www.ncbi.nlm.nih.gov/pubmed/29780651", "http://www.ncbi.nlm.nih.gov/pubmed/29039102", "http://www.ncbi.nlm.nih.gov/pubmed/29056305", "http://www.ncbi.nlm.nih.gov/pubmed/28951472", "http://www.ncbi.nlm.nih.gov/pubmed/24672024", "http://www.ncbi.nlm.nih.gov/pubmed/31039345", "http://www.ncbi.nlm.nih.gov/pubmed/23217619" ], "ideal_answer": [ "A cytokine storm is an undesirable elevation of cytokine levels, as may occur in response to a drug or a device, may lead to severe side effects such as systemic inflammatory response syndrome.", "Cytokine storm is a poorly explained clinical entity caused by an undesired and aggrandized immune system response leading to unregulated activation of the proinflammatory cascade, often contributing to multisystem organ failure and even death", "Cytokine storm is a poorly understood clinical entity caused by an undesired and ag grandized immune system response leading to unregulated activation of the proinflammatory cascade, often contributing to multisystem organ failure and even death." ], "type": "summary", "id": "5e3ac64eb5b409ea5300001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 474, "text": "Endotoxins and exotoxins are among the most potent bacterial inducers of cytokines. During infectious processes, the production of inflammatory cytokines including tumor necrosis factor (TNF), interleukin-1\u03b2 (IL-1\u03b2), gamma interferon (IFN\u03b3) and chemokines orchestrates the anti-infectious innate immune response. However, an overzealous production, leading up to a cytokine storm, can be deleterious and contributes to mortality consecutive to sepsis or toxic shock syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056305", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 535, "text": "undesirable elevation of cytokine levels, as may occur in response to a drug or a device, may lead to severe side effects such as systemic inflammatory response syndrome or cytokine storm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29039102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Cytokine storm is a poorly explained clinical entity caused by an undesired and aggrandized immune system response leading to unregulated activation of the proinflammatory cascade, often contributing to multisystem organ failure and even death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29780651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "UNLABELLED\n\nThe cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24672024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a \"cytokine storm.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28951472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Cytokine storm defines a dysregulation of and an excessively exaggerated immune response most often accompanying selected viral infections and several autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24728596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The cytokine storm is an aggressive immune response characterized by the recruitment of inflammatory leukocytes and exaggerated levels of cytokines and chemokines at the site of infection . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23217619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The cytokine storm is an intensified , dysregulated , tissue-injurious inflammatory response driven by cytokine and immune cell components . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24672024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Cytokine storm is a poorly explained clinical entity caused by an undesired and aggrandized immune system response leading to unregulated activation of the proinflammatory cascade , often contributing to multisystem organ failure and even death . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29780651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Cytokine storm is an immune reaction to an acute or chronic injury and may be caused by a disease itself or by treatment directed at an underlying disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20736486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Cytokine storm defines a dysregulation of and an excessively exaggerated immune response most often accompanying selected viral infections and several autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24728596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "UNLABELLED\nThe cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24672024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "UNLABELLED: The cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24672024", "endSection": "abstract" } ] }, { "body": "Which database exists that contains regulatory SNPs which affect predicted transcription factor binding site affinity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27899579" ], "ideal_answer": [ "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor.", "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites.", "SN2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor.", "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs." ], "exact_answer": [ "SNP2TFBS" ], "type": "factoid", "id": "5e49c2356d0a277941000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1101, "text": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1057, "text": "SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "title" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1058, "text": "SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899579", "endSection": "abstract" } ] }, { "body": "Which R package has been developed for MS-based label-free phosphoproteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28968644" ], "ideal_answer": [ "Phosphonormalizer is an R package for normalization of MS-based label-free phosphoproteomics.", "Phosphonormalizer is a commonly used normalization approach in mass spectrometry-based label-free proteomics. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples.", "Global centering-based normalization is a commonly used normalization approach in mass spectrometry-based label-free proteomics. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples. However, especially in phosphoproteomics, this assumption can introduce bias, as the samples are enriched during sample preparation which can mask the underlying biological changes. To address this possible bias, phosphopeptides quantified in both enriched and non-enriched samples can be used to calculate factors that mitigate the bias. Phosphonormalizer is an R package for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics.", "Phosphonormalizer is an R package for MS-based label-free phosphoproteomics based on mass spectrometry-based normalization. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples." ], "exact_answer": [ "Phosphonormalizer" ], "type": "factoid", "id": "5e52a4ec6d0a277941000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Phosphonormalizer: an R package for normalization of MS-based label-free phosphoproteomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 961, "text": "Global centering-based normalization is a commonly used normalization approach in mass spectrometry-based label-free proteomics. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples. However, especially in phosphoproteomics, this assumption can introduce bias, as the samples are enriched during sample preparation which can mask the underlying biological changes. To address this possible bias, phosphopeptides quantified in both enriched and non-enriched samples can be used to calculate factors that mitigate the bias.Results: We present an R package phosphonormalizer for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics.Availability and implementation: The phosphonormalizer package is freely available under GPL (\u2009>\u2009=2) license from Bioconductor (https://bioconductor.org/packages/phosphonormalizer).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 782, "text": "Results\n\nWe present an R package phosphonormalizer for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 779, "text": "Results We present an R package phosphonormalizer for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Phosphonormalizer: an R package for normalization of MS-based label-free phosphoproteomics", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "title" }, { "offsetInBeginSection": 642, "offsetInEndSection": 782, "text": "Results\nWe present an R package phosphonormalizer for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 1096, "text": "To address this possible bias, phosphopeptides quantified in both enriched and non-enriched samples can be used to calculate factors that mitigate the bias.Results: We present an R package phosphonormalizer for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics.Availability and implementation: The phosphonormalizer package is freely available under GPL (\u2009>\u2009=2) license from Bioconductor (https://bioconductor.org/packages/phosphonormalizer).Contact: sohrab.saraei@utu.fi or laura.elo@utu.fi.Supplementary information: Supplementary data are available at Bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 760, "text": "We present an R package phosphonormalizer for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968644", "endSection": "abstract" } ] }, { "body": "Is there a vaccine for peanut allergy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30319619", "http://www.ncbi.nlm.nih.gov/pubmed/25459578", "http://www.ncbi.nlm.nih.gov/pubmed/26288733" ], "ideal_answer": [ "Yes, there is a vaccine for peanut allergy.", "yes, there is currently a vaccine being tested for peanut allergies." ], "exact_answer": "yes", "type": "yesno", "id": "5e46bdcd3f54159529000007", "snippets": [ { "offsetInBeginSection": 275, "offsetInEndSection": 483, "text": "Currently, two forms of peanut immunotherapy, oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT), are in Phase III clinical trials and have shown promise to induce desensitization in many subjects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30319619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "This article presents an overview of potential treatments of food allergy, with an emphasis on various forms of immunotherapy (including oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, immunotherapy with modified food antigens, and immunotherapy with a recombinant peanut vaccine).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25459578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Recent advances in immunotherapy and vaccine development for peanut allergy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26288733", "endSection": "title" }, { "offsetInBeginSection": 561, "offsetInEndSection": 624, "text": "Efforts have been made to develop a vaccine for peanut allergy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26288733", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 964, "text": "So far, results, especially from oral immunotherapy studies, have shown good efficacy in achieving desensitization to peanut with a good safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26288733", "endSection": "abstract" } ] }, { "body": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22546085", "http://www.ncbi.nlm.nih.gov/pubmed/27712624", "http://www.ncbi.nlm.nih.gov/pubmed/31375588", "http://www.ncbi.nlm.nih.gov/pubmed/29329682", "http://www.ncbi.nlm.nih.gov/pubmed/30065095", "http://www.ncbi.nlm.nih.gov/pubmed/23865689", "http://www.ncbi.nlm.nih.gov/pubmed/23763835", "http://www.ncbi.nlm.nih.gov/pubmed/29778200", "http://www.ncbi.nlm.nih.gov/pubmed/25701212", "http://www.ncbi.nlm.nih.gov/pubmed/29478397", "http://www.ncbi.nlm.nih.gov/pubmed/26656689" ], "ideal_answer": [ "The virus that causes FIP, Feline Infectious Peritonitis belongs to the family coronavirus.", "Feline coronavirus (fcov) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (fip).", "Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP)", "Feline Infectious Peritonitis (FIP) belongs to the family of coronavirus.", "Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats.", "Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats", "Feline Infectious Peritonitis virus (FIP) belongs to the coronavirus family of the genus Flavivirus which cause central nervous system disease.", "Feline infectious peritonitis (FIP) is a cat virus caused by a member of the coronavirus family coronaviruses." ], "exact_answer": [ "Coronavirus" ], "type": "factoid", "id": "5e3eba5548dab47f26000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29778200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29329682", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 247, "text": "Feline coronavirus (FCoV) infection is very common in cats, usually causing only mild intestinal signs such as diarrhoea. Up to 10% of FCoV infections, however, result in the fatal disease feline infectious peritonitis (FIP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29478397", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 350, "text": "Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656689", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 412, "text": "The causative agent of this deadly disease, feline infectious peritonitis virus (FIPV), arises from feline enteric coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27712624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23865689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Feline infectious peritonitis virus (FIP virus: FIPV), a feline coronavirus of the family Coronaviridae, causes a fatal disease called FIP in wild and domestic cat species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Feline infectious peritonitis (FIP) is one of the most important infectious diseases in cats and is caused by feline coronavirus (FCoV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31375588", "endSection": "abstract" }, { "offsetInBeginSection": 1642, "offsetInEndSection": 1824, "text": "IMPORTANCE Feline coronavirus (FCoV) is one of the most significant coronaviruses, because this virus induces feline infectious peritonitis (FIP), which is a lethal disease in cats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31375588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Feline infectious peritonitis (FIP), one of the most important lethal infections of cats, is caused by feline infectious peritonitis virus (FIPV), the high-virulence biotype of feline coronaviruses (FCoVs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30065095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The feline infectious peritonitis virus ( FIPV ) is a member of the feline coronavirus family that causes FIP , which is incurable and fatal in cats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22546085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Feline infectious peritonitis virus ( FIP virus: FIPV) , a feline coronavirus of the family Coronaviridae , causes a fatal disease called FIP in wild and domestic cat species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701212", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 350, "text": "Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656689", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 413, "text": "The causative agent of this deadly disease, feline infectious peritonitis virus (FIPV), arises from feline enteric coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27712624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23763835", "endSection": "abstract" } ] }, { "body": "What is a \"cytokine storm\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29307884", "http://www.ncbi.nlm.nih.gov/pubmed/29455535", "http://www.ncbi.nlm.nih.gov/pubmed/28918421", "http://www.ncbi.nlm.nih.gov/pubmed/29056305" ], "ideal_answer": [ "During infectious processes, the production of inflammatory cytokines including tumor necrosis factor (TNF), interleukin-1b (IL-1b), gamma interferon (IFNg) and chemokines orchestrates the anti-infectious innate immune response. However, an overzealous production, leading up to a cytokine storm, can be deleterious and contributes to mortality consecutive to sepsis or toxic shock syndrome." ], "type": "summary", "id": "5e807578835f4e4777000028", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 159, "text": "Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory state mediated by uncontrolled cytokine storm and haemophagocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28918421", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 475, "text": "During infectious processes, the production of inflammatory cytokines including tumor necrosis factor (TNF), interleukin-1\u03b2 (IL-1\u03b2), gamma interferon (IFN\u03b3) and chemokines orchestrates the anti-infectious innate immune response. However, an overzealous production, leading up to a cytokine storm, can be deleterious and contributes to mortality consecutive to sepsis or toxic shock syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056305", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 638, "text": "Reactive oxygen species (ROS) are signaling molecules responsible for the production of cytokines and chemokines that can mediate hyperactivation of the immune response called cytokine storm. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29455535", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 179, "text": " cytokine storm leading to severe organ damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29307884", "endSection": "abstract" } ] }, { "body": "Is golimumab effective for sarcoidosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29601563", "http://www.ncbi.nlm.nih.gov/pubmed/25034562" ], "ideal_answer": [ "No, golimumab is not effective for treatment of sarcoidosis." ], "exact_answer": "no", "type": "yesno", "id": "5e476b99d14c9f295d000001", "snippets": [ { "offsetInBeginSection": 526, "offsetInEndSection": 754, "text": "Introduced monoclonal antibodies (infliximab, etanercept, adaluimumab, golimumab, rituximab), tested for efficacy in other pathologies associated with the formation of granulomas, have a limited application in patients with SA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29601563", "endSection": "abstract" }, { "offsetInBeginSection": 1399, "offsetInEndSection": 1520, "text": "Although treatment was well tolerated, neither ustekinumab nor golimumab demonstrated efficacy in pulmonary sarcoidosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25034562", "endSection": "abstract" }, { "offsetInBeginSection": 1399, "offsetInEndSection": 1519, "text": "Although treatment was well tolerated, neither ustekinumab nor golimumab demonstrated efficacy in pulmonary sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25034562", "endSection": "abstract" } ] }, { "body": "Is SARS virus interacting with ACE2 encoded protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26487711", "http://www.ncbi.nlm.nih.gov/pubmed/27082314", "http://www.ncbi.nlm.nih.gov/pubmed/29190287", "http://www.ncbi.nlm.nih.gov/pubmed/30356097", "http://www.ncbi.nlm.nih.gov/pubmed/30102747" ], "ideal_answer": [ "Yes,\nThe infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)." ], "exact_answer": "yes", "type": "yesno", "id": "5e80675d835f4e4777000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30102747", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 369, "text": "The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30356097", "endSection": "abstract" }, { "offsetInBeginSection": 1538, "offsetInEndSection": 1690, "text": "Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29190287", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 1145, "text": "Angiotensin-converting enzyme 2 (ACE2), a relatively new member of the RAS, has drawn extensive attention since 2003, because of the findings that ACE2 is the receptor for SARS Corona virus and that maintenance of normal ACE2 levels in the lung is beneficial for the host to combat inflammatory lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27082314", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 345, "text": "The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26487711", "endSection": "abstract" } ] }, { "body": "What is Soluvia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22149703" ], "ideal_answer": [ "Soluvia(tm) by Becton Dickinson is a microinjection system for intradermal delivery of vaccines." ], "type": "summary", "id": "5e7f5f1a835f4e4777000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "On May 9 2011, the US FDA approved Sanofi Pasteur's Fluzone(\u00ae) Intradermal influenza vaccine, the first influenza vaccine licensed in the USA that uses a new microinjection system for intradermal delivery of vaccines (Soluvia\u2122, Becton Dickinson). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22149703", "endSection": "abstract" } ] }, { "body": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22280883", "http://www.ncbi.nlm.nih.gov/pubmed/24209771", "http://www.ncbi.nlm.nih.gov/pubmed/24707494", "http://www.ncbi.nlm.nih.gov/pubmed/26822958", "http://www.ncbi.nlm.nih.gov/pubmed/27027316", "http://www.ncbi.nlm.nih.gov/pubmed/23964891", "http://www.ncbi.nlm.nih.gov/pubmed/19889934", "http://www.ncbi.nlm.nih.gov/pubmed/30691609" ], "ideal_answer": [ "yes, Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection.", "Yes. The FIP virus is a mutated strain of the Feline enteric Coronavirus (FECV) causing infectious peritonitis and neoplasia", " Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection.", " Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection.", "Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection.", "Yes. The FIP virus is a mutated strain of the Feline enteric coronavirus (FECV) infects cats, and is thought to be a newly identified strain with heterozygous mutations that create a K27M amino acid substitution." ], "exact_answer": "yes", "type": "yesno", "id": "5e3ebaa348dab47f2600000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26822958", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 194, "text": "It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24707494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22280883", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 597, "text": "Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27027316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV), a virulent mutant of apathogenic feline enteric coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19889934", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30691609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND\n\nFeline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24209771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "BACKGROUND Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24209771", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 245, "text": "This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22280883", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 569, "text": "Whilst intact in all FECVs, the 3c gene was mutated in the majority (71.4 %) of FIPVs, but not in all, implying that mutation in 3c is not the (single) cause of FIP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19889934", "endSection": "abstract" } ] }, { "body": "Does SATB1 regulate the RAG1 and RAG2 genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25847946", "http://www.ncbi.nlm.nih.gov/pubmed/9886398" ], "ideal_answer": [ "SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters.", "An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression", "High level expression of the Xlr nuclear protein in immature thymocytes and colocalization with the matrix-associated region-binding SATB1 protein Its onset preceded the rearrangement of TCR genes, as Xlr expression was conserved in thymus cells from RAG1(0/0) mice. An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters.", " SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes.", "An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.", " Its onset preceded the rearrangement of TCR genes, as Xlr expression was conserved in thymus cells from RAG1(0/0) mice. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters.", "An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters." ], "exact_answer": "yes", "type": "yesno", "id": "5d36bb777bc3fee31f00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "High level expression of the Xlr nuclear protein in immature thymocytes and colocalization with the matrix-associated region-binding SATB1 protein", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886398", "endSection": "title" }, { "offsetInBeginSection": 527, "offsetInEndSection": 648, "text": " Its onset preceded the rearrangement of TCR genes, as Xlr expression was conserved in thymus cells from RAG1(0/0) mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25847946", "endSection": "title" }, { "offsetInBeginSection": 793, "offsetInEndSection": 961, "text": " SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25847946", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1148, "text": "Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25847946", "endSection": "abstract" } ] }, { "body": "What is the main difference between nascent and mature chromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6226660", "http://www.ncbi.nlm.nih.gov/pubmed/7171565", "http://www.ncbi.nlm.nih.gov/pubmed/1893943" ], "ideal_answer": [ "Nascent chromatin is created after transcription and is mostly lacking histone modifications and H1, which makes it more prone to digestion by DNaseI.", " Like normal nascent chromatin, chromatin labeled for brief periods (0.5-1 min) in the presence of butyrate was more sensitive to digestion with DNase I and micrococcal nuclease than control bulk chromatin. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin).", "The nascent and mature forms of chromatin differ in two aspects of their histone modifications: polycistronic messengers are expressed as a sequence of individual nucleosomes only in mature chromatin, and the nucleosome is involved in both transcription and repair processes.", " The second class of nascent DNA is distinguished from the nucleosomal component by its insolubility, lack of discernible nucleosomal organization, and dependence on protein synthesis to attain typical subunit structure Like normal nascent chromatin, chromatin labeled for brief periods (0.5-1 min) in the presence of butyrate was more sensitive to digestion with DNase I and micrococcal nuclease than control bulk chromatin. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin). Incubation of mature chromatin in butyrate for 1 h did not induce DNase I sensitivity: therefore, the presence of sodium butyrate was required during replication to preserve the increased digestibility of nascent chromatin DNA In a previous study (Perry and Annunziato, Nucleic Acids Res. Within 10 min of DNA synthesis, the spacing of mature chromatin is established; the spacing maturation can occur in the absence of protein synthesis. this class of nascent chromatin exhibits a shortened repeat length of approximately 165 bp, as opposed to the 288-bp repeat of bulk chromatin.", "Mature and nascent chromatin differ in two aspects of their histone modifications: polycistronic messengers are expressed as a sequence of individual nucleosomes only in mature cells, and they are preferentially expressed in the later stages of cell development.", "In a previous study (Perry and Annunziato, Nucleic Acids Res. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin)." ], "exact_answer": [ "lack of H1" ], "type": "factoid", "id": "5d38577b7bc3fee31f000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Maturation of nucleosomal and nonnucleosomal components of nascent chromatin: differential requirements for concurrent protein synthesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7171565", "endSection": "title" }, { "offsetInBeginSection": 433, "offsetInEndSection": 944, "text": "this class of nascent chromatin exhibits a shortened repeat length of approximately 165 bp, as opposed to the 288-bp repeat of bulk chromatin. Within 10 min of DNA synthesis, the spacing of mature chromatin is established; the spacing maturation can occur in the absence of protein synthesis. The second class of nascent DNA is distinguished from the nucleosomal component by its insolubility, lack of discernible nucleosomal organization, and dependence on protein synthesis to attain typical subunit structure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7171565", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 525, "text": " Like normal nascent chromatin, chromatin labeled for brief periods (0.5-1 min) in the presence of butyrate was more sensitive to digestion with DNase I and micrococcal nuclease than control bulk chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6226660", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 916, "text": "Incubation of mature chromatin in butyrate for 1 h did not induce DNase I sensitivity: therefore, the presence of sodium butyrate was required during replication to preserve the increased digestibility of nascent chromatin DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6226660", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 551, "text": "In a previous study (Perry and Annunziato, Nucleic Acids Res. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1893943", "endSection": "abstract" } ] }, { "body": "Is CTCF bound at nucleosome free regions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30188887", "http://www.ncbi.nlm.nih.gov/pubmed/21249180", "http://www.ncbi.nlm.nih.gov/pubmed/16877759", "http://www.ncbi.nlm.nih.gov/pubmed/30414923", "http://www.ncbi.nlm.nih.gov/pubmed/25348714" ], "ideal_answer": [ "yes, robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites", "nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin.", "robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites", "Nucleosome occupancy at nucleosome-free regions (nfrs), many of which are located at sites occupied by the multivalent factors ctcf and cohesin. This general architectural change correlate with enhanced binding of ct cf and more pronounced insulation across chromatin boundaries in lineage-committed cells.", "Nucleosome occupancy is reduced at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors CTCF and cohesin. Robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites" ], "exact_answer": "yes", "type": "yesno", "id": "5d371ec97bc3fee31f00000c", "snippets": [ { "offsetInBeginSection": 928, "offsetInEndSection": 1081, "text": "Nucleosome depletion at 5'-HS4 was dependent on interaction of the insulator protein CCCTC-binding factor (CTCF) and was required for enhancer blocking. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16877759", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 946, "text": "Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249180", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1130, "text": "hese differences extend to histone variants (H2A.Z) and marks (H3K4 methylation), as well as insulator binding (such as CTCF), independent of the expression levels of affected genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21249180", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 649, "text": "nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25348714", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 772, "text": "This general architectural change correlates with enhanced binding of CTCF and cohesins and more pronounced insulation of contacts across chromatin boundaries in lineage-committed cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30414923", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 837, "text": "robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30188887", "endSection": "abstract" } ] }, { "body": "Is bortezomib a Proteasome inhibitor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26288836", "http://www.ncbi.nlm.nih.gov/pubmed/22702336", "http://www.ncbi.nlm.nih.gov/pubmed/28409734", "http://www.ncbi.nlm.nih.gov/pubmed/16278210", "http://www.ncbi.nlm.nih.gov/pubmed/31088925", "http://www.ncbi.nlm.nih.gov/pubmed/22027222", "http://www.ncbi.nlm.nih.gov/pubmed/21247388", "http://www.ncbi.nlm.nih.gov/pubmed/22216088", "http://www.ncbi.nlm.nih.gov/pubmed/28860152", "http://www.ncbi.nlm.nih.gov/pubmed/28317148" ], "ideal_answer": [ "The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. Proteasome inhibitor bortezomib", "Yes, bortezomib is a Proteasome inhibitor.", "Yes, bortezomib is a potent and specific reversible ubiquitin/proteasome inhibitor.", "yes, The proteasome-inhibitor bortezomib", "Yes bortezomib is a Proteasome inhibitor.", "proteasome inhibitor bortezomib", "The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for gbm.", "Proteasome inhibitor bortezomib" ], "exact_answer": "yes", "type": "yesno", "id": "5e3c6850b5b409ea5300001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 35, "text": "The proteasome-inhibitor bortezomib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28317148", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 249, "text": "The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28409734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 32, "text": "Proteasome inhibitor bortezomib ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28860152", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22027222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Regulation of osteoblastic differentiation by the proteasome inhibitor bortezomib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22702336", "endSection": "title" }, { "offsetInBeginSection": 216, "offsetInEndSection": 446, "text": "The proteasome inhibitor bortezomib (also known as Velcade and PS-341) is a clinically effective antineoplastic drug that is FDA approved for treatment of hematologic malignancies such as multiple myeloma and mantle cell lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31088925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21247388", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The proteasome inhibitor bortezomib is emerging as a potent anti-cancer agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16278210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Bortezomib (Velcade\u2122) is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22216088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "The proteasome inhibitor Bortezomib is used to treat multiple myeloma (MM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26288836", "endSection": "abstract" } ] }, { "body": "Is PRDM9 essential for meiosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29674518", "http://www.ncbi.nlm.nih.gov/pubmed/19997497", "http://www.ncbi.nlm.nih.gov/pubmed/24634223", "http://www.ncbi.nlm.nih.gov/pubmed/23190393", "http://www.ncbi.nlm.nih.gov/pubmed/30161134", "http://www.ncbi.nlm.nih.gov/pubmed/29478809" ], "ideal_answer": [ "PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis.", "In aggregate, our data indicate that domains typically involved in regulation of gene expression do not serve that role in PRDM9, but are likely involved in setting the proper chromatin environment for initiation and completion of homologous recombination. PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.", "yes, Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis", "Prdm9, is a meiosis-specific protein that trimethylates h3k4 and controls the activation of recombination hot spots. It is an essential enzyme in the progression of early meiotic prophase.", "Yes. PRDM9 is an evolutionarily conserved protein that is essential for meiosis.", "In many eukaryotes, sites of meiotic recombination, also called hotspots, are regions of accessible chromatin, but in many vertebrates, their location follows a distinct pattern and is specified by PR domain-containing protein 9 (PRDM9). PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.", "Yes, PRDM9 is essential for meiosis.", "Yes. PRDM9 is an RNA-binding protein that is essential for meiosis.", "Yes. PRDM9 is an essential factor for meiosis.", "PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.", "PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis. PRDM9 (PR domain-containing protein 9) is a meiosis-specific protein that trimethylates H3K4 and controls the activation of recombination hot spots." ], "exact_answer": "yes", "type": "yesno", "id": "5d3856ca7bc3fee31f000016", "snippets": [ { "offsetInBeginSection": 1468, "offsetInEndSection": 1639, "text": "Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19997497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "PRDM9 gene polymorphism may not be associated with defective spermatogenesis in the Chinese Han population", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190393", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23190393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "PRDM9 (PR domain-containing protein 9) is a meiosis-specific protein that trimethylates H3K4 and controls the activation of recombination hot spots. It is an essential enzyme in the progression of early meiotic prophase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24634223", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 404, "text": "In many eukaryotes, sites of meiotic recombination, also called hotspots, are regions of accessible chromatin, but in many vertebrates, their location follows a distinct pattern and is specified by PR domain-containing protein 9 (PRDM9). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30161134", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 1252, "text": " We found that although the post-SET zinc finger and the KRAB domains are not essential for the methyltransferase activity of PRDM9 in cell culture, the KRAB domain mutant mice show only residual PRDM9 methyltransferase activity and undergo meiotic arrest. In aggregate, our data indicate that domains typically involved in regulation of gene expression do not serve that role in PRDM9, but are likely involved in setting the proper chromatin environment for initiation and completion of homologous recombination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29674518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29478809", "endSection": "title" } ] }, { "body": "What is particular about the mouse Fxy gene's chromosomal position?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10644436", "http://www.ncbi.nlm.nih.gov/pubmed/9425238", "http://www.ncbi.nlm.nih.gov/pubmed/10508587" ], "ideal_answer": [ "We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species.", "The gene Fxy (also known as MID1 [7]) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes", "We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. ", "The mouse fxy gene spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the x chromosome, but the remainder is located on both x and y chromosomes.", "The gene Fxy (also known as MID1) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes.", "The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, called FXY2, which also maps to the X chromosome within Xq22" ], "type": "summary", "id": "5d387e24a1e1595105000011", "snippets": [ { "offsetInBeginSection": 231, "offsetInEndSection": 469, "text": "We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9425238", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 879, "text": "The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, called FXY2, which also maps to the X chromosome within Xq22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10644436", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 986, "text": "The gene Fxy (also known as MID1 [7]) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10508587", "endSection": "abstract" } ] }, { "body": "Should Pentoxifylline be used for treatment of amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16401852" ], "ideal_answer": [ "No. Pentoxifylline is not beneficial in amyotrophic lateral sclerosis and should be avoided in patients treated with riluzole." ], "exact_answer": "no", "type": "yesno", "id": "5e4b5f9a6d0a277941000021", "snippets": [ { "offsetInBeginSection": 748, "offsetInEndSection": 1089, "text": ".RESULTS: At the end of the study, after 547 days of follow-up, 103 patients (51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02). In contrast, analysis of secondary outcome functional variables did not show the same negative effect of the drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16401852", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1310, "text": "CONCLUSIONS: Pentoxifylline is not beneficial in ALS and should be avoided in patients treated with riluzole. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16401852", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 973, "text": "RESULTS: At the end of the study, after 547 days of follow-up, 103 patients (51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16401852", "endSection": "abstract" } ] }, { "body": "What does a PET (Positron Excitation Tomography) measure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9439081", "http://www.ncbi.nlm.nih.gov/pubmed/23575833", "http://www.ncbi.nlm.nih.gov/pubmed/18988199", "http://www.ncbi.nlm.nih.gov/pubmed/2101731", "http://www.ncbi.nlm.nih.gov/pubmed/28168704" ], "ideal_answer": [ "Positron Excitation Tomography (PET) is a simple, reliable, and valid method of assessing brain activity in patients with Parkinson's disease (PD).", "Positron emission tomography pet (pet) is used to measure changes in regional brain glucose metabolism. It is used for the quantitative measurement of regional cerebral flow in awake rats.", "Positron emission tomography (PET) allows the quantitative measurement of regional cerebral flow (rCBF) in humans in quantitative terms", "Positron Excitation Tomography (PET) is a method that uses photoreactive nucleotides (Percutaneous Transluminal Angioplasty) to detect structural changes in the central nervous system (CNS) following ischemic injury.", "Positron emission tomography (PET) is used to measure differences in metabolism in different tissues.", "Positron Excitation Tomography (PET) is a method that allows for quantitative assessment of brain injury conditions such as multiple system atrophy.", "Positron emission tomography (PET) with [(18)F]2-fluoro-2-deoxy-D-glucose was used to measure changes in regional brain glucose metabolism" ], "type": "summary", "id": "5e4025f148dab47f2600000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Positron emission tomography (PET) with [(18)F]2-fluoro-2-deoxy-D-glucose was used to measure changes in regional brain glucose metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23575833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Mapping brain metabolic connectivity in awake rats with \u03bcPET and optogenetic stimulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23575833", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Positron emission tomography (PET) allows the quantitative measurement of regional cerebral flow (rCBF) in humans in quantitative terms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9439081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Positron emission tomography (PET) allows the quantitative measurement of regional cerebral flow (rCBF) in humans in quantitative terms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9439081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "PURPOSE\n\nPositron emission tomography (PET) is a useful imaging modality that quantifies the physiological distributions of radiolabeled tracers in\u00a0vivo in humans and animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28168704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "PURPOSE\nPositron emission tomography (PET) is a useful imaging modality that quantifies the physiological distributions of radiolabeled tracers in\u00a0vivo in humans and animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28168704", "endSection": "abstract" } ] }, { "body": "Is the CADM2 gene associated with differences in information processing speed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28797215", "http://www.ncbi.nlm.nih.gov/pubmed/25869804" ], "ideal_answer": [ "Yes, genetic variation in the CADM2 gene is associated with individual differences in information processing speed.", "Yes. Genetic variation in the CADM2 gene is associated with individual differences in information processing speed.", "Yes, changes in the CADM2 gene have been associated with differences in information processing speed." ], "exact_answer": "yes", "type": "yesno", "id": "5e52bc986d0a277941000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "GWAS for executive function and processing speed suggests involvement of the CADM2 gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25869804", "endSection": "title" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1888, "text": "A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 \u00d7 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 \u00d7 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 \u00d7 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 \u00d7 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 \u00d7 10(-11)) and neuron cell-cell adhesion (P-value=1.48 \u00d7 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25869804", "endSection": "abstract" }, { "offsetInBeginSection": 1752, "offsetInEndSection": 1888, "text": "Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25869804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "The CADM2 gene is associated with processing speed performance - evidence among elderly with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28797215", "endSection": "title" }, { "offsetInBeginSection": 1752, "offsetInEndSection": 1889, "text": "Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25869804", "endSection": "abstract" } ] }, { "body": "What is GeneCodeq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27354700" ], "ideal_answer": [ "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy.", "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy.", "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy. The method leverages a corpus of k-mers to reduce the entropy of the quality scores and thereby the compressibility of these data (in FASTQ or SAM/BAM/CRAM files), resulting in compression ratios that significantly exceeds those of other methods." ], "type": "summary", "id": "5e52af9e6d0a277941000048", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "GeneCodeq: quality score compression and improved genotyping using a Bayesian framework.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1574, "text": "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses.RESULTS: We here propose GeneCodeq, a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy. Our model leverages a corpus of k-mers to reduce the entropy of the quality scores and thereby the compressibility of these data (in FASTQ or SAM/BAM/CRAM files), resulting in compression ratios that significantly exceeds those of other methods. Our approach can also be combined with existing lossy compression schemes to further reduce entropy and allows the user to specify a reference panel of expected sequence variations to improve the model accuracy. In addition to extensive empirical evaluation, we also derive novel theoretical insights that explain the empirical performance and pitfalls of corpus-based quality score compression schemes in general. Finally, we show that as a positive side effect of compression, the model can lead to improved genotyping accuracy.AVAILABILITY AND IMPLEMENTATION: GeneCodeq is available at: github.com/genecodeq/eval", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "GeneCodeq: quality score compression and improved genotyping using a Bayesian framework", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354700", "endSection": "title" } ] }, { "body": "Is Nivolumab (Opdivo) a PD-L1 inhibitor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30171077", "http://www.ncbi.nlm.nih.gov/pubmed/27313464", "http://www.ncbi.nlm.nih.gov/pubmed/28833116", "http://www.ncbi.nlm.nih.gov/pubmed/26514815" ], "ideal_answer": [ "No, Nivolumab (Opdivo) is a PD-1 inhibitor.", "Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab" ], "exact_answer": "no", "type": "yesno", "id": "5e494cf96d0a277941000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28833116", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 565, "text": " PD-1 inhibitor nivolumab (Opdivo)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28833116", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 161, "text": "programmed cell death protein 1 (PD-1)-blocking antibodies nivolumab or pembrolizumab ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30171077", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 332, "text": "An improvement in the understanding of the role of the immune system in tumor immunosurveillance has led to the development of the programmed death-1 ( PD-1 ) immune checkpoint inhibitor nivolumab ( Opdivo) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27313464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Nivolumab (Opdivo(\u00ae); Nivolumab BMS\u2122) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26514815", "endSection": "abstract" } ] }, { "body": "Does clinical trial data support the use of minocycline for amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15159491", "http://www.ncbi.nlm.nih.gov/pubmed/17980667", "http://www.ncbi.nlm.nih.gov/pubmed/16193258", "http://www.ncbi.nlm.nih.gov/pubmed/16638021", "http://www.ncbi.nlm.nih.gov/pubmed/18802797" ], "ideal_answer": [ "No. Available clinical trial data suggest that minocycline does not improve prognosis and functional status, and has a harmful effect on patients with amyotrophic lateral sclerosis." ], "exact_answer": "no", "type": "yesno", "id": "5e4b5fd86d0a277941000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Two double-blind, randomized, placebo-controlled feasibility trials of minocycline in ALS were conducted. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15159491", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 918, "text": "This pilot study shows that minocycline and riluzole can be taken safely together. Further trials are needed to assess efficacy of such treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16193258", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 283, "text": "It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16638021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980667", "endSection": "title" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1514, "text": "FINDINGS: ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (-1.30 vs -1.04 units/month, 95% CI for difference -0.44 to -0.08; p=0.005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980667", "endSection": "abstract" }, { "offsetInBeginSection": 1725, "offsetInEndSection": 1989, "text": "INTERPRETATION: Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community. As on previous occasions, the results obtained in the laboratory are not reproduced in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18802797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18802797", "endSection": "abstract" }, { "offsetInBeginSection": 1731, "offsetInEndSection": 1995, "text": "INTERPRETATION\n\nOur finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18802797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "A recent publication of the results of a clinical trial of minocycline in 412 ALS patient has aroused considerable controversy in the ALS scientific community.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18802797", "endSection": "abstract" }, { "offsetInBeginSection": 1697, "offsetInEndSection": 1945, "text": "Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980667", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1416, "text": "Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17980667", "endSection": "abstract" } ] }, { "body": "What are apoptotic bodies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29518372", "http://www.ncbi.nlm.nih.gov/pubmed/28684288", "http://www.ncbi.nlm.nih.gov/pubmed/29181712", "http://www.ncbi.nlm.nih.gov/pubmed/28766167", "http://www.ncbi.nlm.nih.gov/pubmed/29616307" ], "ideal_answer": [ "Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular space by almost all types of cells. EVs can cross the physiological barriers, and a variety of biological fluids are enriched in them. EVs are a heterogeneous population of vesicles, including exosomes, microvesicles, and apoptotic bodies.\nApoptotic bodies are generated on apoptotic cell shrinkage and death." ], "type": "summary", "id": "5e81cb50835f4e477700002f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular space by almost all types of cells. EVs can cross the physiological barriers, and a variety of biological fluids are enriched in them. EVs are a heterogeneous population of vesicles, including exosomes, microvesicles, and apoptotic bodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29616307", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 447, "text": "Extracellular vesicles (EVs), microparticles, exosomes, and apoptotic bodies, originated by different cell types are emerging as a novel mean of cell-to-cell communication in physiology and pathology and represent a new way to convey fundamental information between cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29518372", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 612, "text": "Apoptotic bodies are generated on apoptotic cell shrinkage and death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28684288", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 527, "text": " In treated cells, the apoptotic hallmarks such as formation of apoptotic bodies, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28766167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Extracellular vesicles are cell-derived membrane particles ranging from 30 to 5,000\u00a0nm in size, including exosomes, microvesicles, and apoptotic bodies. They are released under physiological conditions, but also upon cellular activation, senescence, and apoptosis. They play an important role in intercellular communication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29181712", "endSection": "abstract" } ] }, { "body": "Is the drug Exubera currently (March 2020) available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25485886" ], "ideal_answer": [ "No, Exubera has been discontinued due to suboptimal market acceptance." ], "exact_answer": "no", "type": "yesno", "id": "5e776a10835f4e477700000c", "snippets": [ { "offsetInBeginSection": 196, "offsetInEndSection": 446, "text": "Despite discontinuation of the first inhalable insulin, Exubera\u00ae, due to suboptimal market acceptance, development of orally inhaled insulin delivery systems has been galvanized by the recent approval of Afrezza\u00ae and several others awaiting approval.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25485886", "endSection": "abstract" } ] }, { "body": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22922743", "http://www.ncbi.nlm.nih.gov/pubmed/26861626" ], "ideal_answer": [ "eviction of h1", "Chd1 and chd1 atp-dependent chromatin remodelers compete to set nucleosome spacing in vivo.", "The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo. CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing.", "In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing.", "The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo", "We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin", "CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing", "The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing" ], "type": "summary", "id": "5d3880eea1e1595105000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861626", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 410, "text": "In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861626", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 691, "text": "CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861626", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1173, "text": "We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861626", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 828, "text": "Isw1b acts in conjunction with Chd1 to regulate chromatin structure by preventing trans-histone exchange from taking place over coding regions. In this way, Isw1b and Chd1 are important in maintaining chromatin integrity during transcription elongation by RNAPII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922743", "endSection": "abstract" } ] }, { "body": "Are breaks in double stranded DNA associated with ionizing radiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10639091", "http://www.ncbi.nlm.nih.gov/pubmed/1540967", "http://www.ncbi.nlm.nih.gov/pubmed/16650867", "http://www.ncbi.nlm.nih.gov/pubmed/31652722", "http://www.ncbi.nlm.nih.gov/pubmed/9665145", "http://www.ncbi.nlm.nih.gov/pubmed/29043625", "http://www.ncbi.nlm.nih.gov/pubmed/26089209", "http://www.ncbi.nlm.nih.gov/pubmed/20079875", "http://www.ncbi.nlm.nih.gov/pubmed/6445538", "http://www.ncbi.nlm.nih.gov/pubmed/29787435", "http://www.ncbi.nlm.nih.gov/pubmed/29956296", "http://www.ncbi.nlm.nih.gov/pubmed/7683090", "http://www.ncbi.nlm.nih.gov/pubmed/23948232" ], "ideal_answer": [ "Yes, double-strand breaks in double stranded DNA may be associated with ionizing radiation risk.", "Yes, breaks in double stranded DNA are associated with ionizing radiation." ], "exact_answer": "yes", "type": "yesno", "id": "5e3c6e15b5b409ea53000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "DNA double-strand breaks (DSBs) are major DNA lesions that are constantly formed during physiological processes such as DNA replication, transcription, and recombination, or as a result of exogenous agents such as ionizing radiation, radiomimetic drugs, and genome editing nucleases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29043625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Whereas most endogenous and exogenous DNA damaging agents typically generate lesions that are relatively isolated and can be repaired easily, ionizing radiation (IR) also induces clustered lesions causing DNA double strand breaks (DSBs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29956296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The induction of DNA interstrand cross-links by ionizing radiation has been largely ignored in favour of studies on double-strand break formation and repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20079875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "While much is known about radiation-induced DNA double-strand breaks (DSBs) and their repair, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23948232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Exposure of cells to ionizing radiation induces DNA double-strand breaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29787435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "DNA double-strand breaks are considered to be the most deleterious lesion induced by ionizing radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7683090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Influence of chromatin structure on the induction of DNA double strand breaks by ionizing radiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1540967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Ionizing radiation and radiomimetic drugs such as bleomycin, calichieamycin, neocarzinostatin chromophore, and other synthetic agents can produce both single and double strand breaks in DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10639091", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 927, "text": "RESULTS BRCA2-defective cells were unable to repair the double-strand DNA breaks induced by ionizing radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9665145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16650867", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 298, "text": "Double-stranded breaks ( DSBs ) are the most injurious type of DNA damage , being induced by ionizing radiation ( IR ) and cytotoxic agents used in cancer treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31652722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Double-stranded breaks ( DSBs ) are cytotoxic DNA lesions caused by oxygen radicals , ionizing radiation , and radiomimetic chemicals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26089209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Gamma-ray irradiation introduces single and/or double strand breaks into the DNA molecule of the cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6445538", "endSection": "abstract" } ] }, { "body": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19145669", "http://www.ncbi.nlm.nih.gov/pubmed/20518663", "http://www.ncbi.nlm.nih.gov/pubmed/20921829", "http://www.ncbi.nlm.nih.gov/pubmed/24597745", "http://www.ncbi.nlm.nih.gov/pubmed/25536554", "http://www.ncbi.nlm.nih.gov/pubmed/7029300", "http://www.ncbi.nlm.nih.gov/pubmed/26436129", "http://www.ncbi.nlm.nih.gov/pubmed/22077339" ], "ideal_answer": [ "Ionizing radiation is commonly associated with lung cancer, prostate cancer, breast cancer, cervical intraepithelial neoplasia and oral squamous cell carcinoma.", "Exposure to ionizing radiation increases the risk for thyroid and breast cancer and leukemia as well as others such as osteosarcoma.", "Breast cancer, multiple myeloma, leukaemia and osteosarcoma are commonly associated with ionizing radiation.", "Breast cancer, multiple myeloma, leukaemia and osteosarcoma are examples of cancers that are commonly associated with ionizing radiation.", "Because latency period for different nosological forms of radiation-induced malignant tumors varies widely, profound attention in further studies should be drawn not only to thyroid, breast cancers and leukemia, but also to malignancies with longer latent period: lung, stomach, colon, ovary, urinary bladder, kidney cancer and multiple myeloma.", "By contrast, osteosarcoma may be caused by external or internal ionizing radiation,", "radiation- induced breast cancer" ], "exact_answer": [ [ "thyroid cancer" ], [ "Breast Cancer" ], [ "leukemia" ], [ "osteosarcoma" ], [ "lung" ], [ "prostate" ], [ "oral" ], [ "stomach" ], [ "colon" ], [ "bladder" ], [ "ovary" ], [ "multiple myeloma" ], [ "kidney" ], [ "esophageal squamous cell carcinoma" ] ], "type": "list", "id": "5e3c69c9b5b409ea53000021", "snippets": [ { "offsetInBeginSection": 1537, "offsetInEndSection": 1882, "text": "Because latency period for different nosological forms of radiation-induced malignant tumors varies widely, profound attention in further studies should be drawn not only to thyroid, breast cancers and leukemia, but also to malignancies with longer latent period: lung, stomach, colon, ovary, urinary bladder, kidney cancer and multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25536554", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1352, "text": "e highest risk of radiation- induced breast cancer is evidenced in the sub-population of female patients who have undergone radiotherapy for either malignant or non-malignant diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19145669", "endSection": "abstract" }, { "offsetInBeginSection": 1442, "offsetInEndSection": 1567, "text": " This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia.FU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26436129", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 502, "text": "By contrast, osteosarcoma may be caused by external or internal ionizing radiation, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7029300", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 366, "text": "Ionizing radiation exposure is a risk factor for development of esophageal squamous cell carcinoma , a histological subtype of esophageal cancer that is highly aggressive and is associated with poor patient prognosis . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22077339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "Breast cancer ( BC ) is the most common type of malignancy in female patients and radio-treatment is the conventional therapy even if a great number of studies reported that enhanced sensitivity to ionizing radiation as measured as chromosome effects is present in a significant proportion of cancer patients , including breast cancer ones . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921829", "endSection": "abstract" }, { "offsetInBeginSection": 2014, "offsetInEndSection": 2196, "text": "Overall, there was a positive association between radiation and the combined category of cancer of the renal parenchyma, renal pelvis and ureters (ERR/Sv = 0.60, 90% CI: 0.09, 1.30).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20518663", "endSection": "abstract" } ] }, { "body": "Is KAT2A involved in Acute myeloid leukemia (AML)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27760321" ], "ideal_answer": [ "Yes. The KAT2A gene encodes a receptor tyrosine kinase that is frequently mutated in human acute myeloid leukemia (AML). Activating mutations in Kat2A in response to aberrations in TRAIL can lead to TRAIL-1 activation, resulting in the up-regulation of key AML genes, such as TGFb1, NF-kB, Akt, IKK-1, FOXO1, ERK1/2 and c-Myc.", "Yes, KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells." ], "exact_answer": "yes", "type": "yesno", "id": "5e52c0c76d0a27794100004b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1120, "text": "Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A as a candidate for downstream study. KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27760321", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1120, "text": "Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27760321", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 908, "text": "KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27760321", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1121, "text": "Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27760321", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 909, "text": "KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27760321", "endSection": "abstract" } ] }, { "body": "What is Idiopathic toe walking?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29881221", "http://www.ncbi.nlm.nih.gov/pubmed/29575996", "http://www.ncbi.nlm.nih.gov/pubmed/18432151", "http://www.ncbi.nlm.nih.gov/pubmed/29571089", "http://www.ncbi.nlm.nih.gov/pubmed/17161602", "http://www.ncbi.nlm.nih.gov/pubmed/30347291", "http://www.ncbi.nlm.nih.gov/pubmed/29664850", "http://www.ncbi.nlm.nih.gov/pubmed/17260610", "http://www.ncbi.nlm.nih.gov/pubmed/31587271", "http://www.ncbi.nlm.nih.gov/pubmed/28705637", "http://www.ncbi.nlm.nih.gov/pubmed/28716514" ], "ideal_answer": [ "Idiopathic toe walking is a pathological gait pattern in which children older than 3 years walk on their tip toes with no contact between the heels and the ground." ], "type": "summary", "id": "5e47612035b8f0833c000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "BACKGROUND: Idiopathic toe walking (ITW) is a diagnosis of exclusion for children walking on their toes with no medical cause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30347291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "INTRODUCTION: Idiopathic toe-walking (ITW) is described as a gait pattern with no contact between the heels and the ground in children older than 3years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28705637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Idiopathic toe walking is a relatively common developmental condition often leading to secondary problems such as pain and muscle contractures in the lower extremities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29575996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND: Children with idiopathic toe-walking, a common pediatric condition, walk some or all of the time on their toes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29664850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND: Idiopathic toe walking is a diagnosis of exclusion characterized by a persistent toe-toe gait pattern after three years of age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Idiopathic toe walking (ITW) is a pathological gait pattern in which children walk on their tip toes with no orthopedic or neurological reason. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29881221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND\n\nIdiopathic toe walking (ITW) is an exclusionary diagnosis given to healthy children who persist in walking on their toes after they should typically have achieved a heel-toe gait.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31587271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND\n\nIdiopathic toe walking is a diagnosis of exclusion characterized by a persistent toe-toe gait pattern after three years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Idiopathic toe walking is a diagnosis of exclusion characterized by a persistent toe-toe gait pattern after three years of age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571089", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 488, "text": "The diagnosis of idiopathic toe walking is a diagnosis of exclusion used for children with persistent toe walking and no associated medical condition . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28716514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Idiopathic toe-walking is a diagnosis of exclusion when a child presents with bilateral toe-to-toe gait.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18432151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: Idiopathic toe walking is a diagnosis of exclusion characterized by a persistent toe-toe gait pattern after three years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Idiopathic toe walking (ITW), considered abnormal after the age of 3 years, is a common complaint seen by medical professionals, especially orthopaedic surgeons and physiotherapists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17161602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Idiopathic toe-walking is defined as persistent toe-walking in a normal child in the absence of developmental, neurological or neuromuscular conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17260610", "endSection": "abstract" } ] }, { "body": "Is NicVAX vaccine effective for smoking cessation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22895958", "http://www.ncbi.nlm.nih.gov/pubmed/22229310", "http://www.ncbi.nlm.nih.gov/pubmed/21270788", "http://www.ncbi.nlm.nih.gov/pubmed/23496672", "http://www.ncbi.nlm.nih.gov/pubmed/24894625" ], "ideal_answer": [ "No. NicVAX vaccine failed to meet the primary endpoint in two large phase III studies, although the correlation of higher abstinence rates in subjects with higher immunity to nicotine was observed. The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support." ], "exact_answer": "no", "type": "yesno", "id": "5e4b639c6d0a277941000027", "snippets": [ { "offsetInBeginSection": 1480, "offsetInEndSection": 1643, "text": "CONCLUSION: The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 290, "text": " First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1479, "text": "FINDINGS: There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR)\u2009=\u20090.89, 95% confidence interval (CI)\u2009=\u20090.62-1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR\u2009=\u20091.03, 95% CI\u2009=\u20090.73-1.46). The top 30% antibody responders, compared to the placebo group, showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 (42.2 versus 33.2%, OR\u2009=\u20091.47, 95% CI\u2009=\u20090.89-2.42)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1218, "text": "Unfortunately, the only vaccine tested in two large, randomized Phase\u00a0III trials, 3'-amino-methyl-nicotine r-exoprotein A conjugate vaccine (NicVAX(\u00ae), Nabi Biopharmaceuticals, MD, USA), did not demonstrate efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23496672", "endSection": "abstract" }, { "offsetInBeginSection": 3042, "offsetInEndSection": 3365, "text": "The RR for 12 month cessation in active and placebo groups was 1.35 (95% Confidence Interval (CI) 0.82 to 2.22) in\u00a0the trial of NIC002\u00a0and 1.74 (95% CI 0.73 to 4.18) in one NicVAX trial. Two Phase III NicVAX trials, for which full results were not available, reported similar quit rates of approximately 11% in both groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22895958", "endSection": "abstract" }, { "offsetInBeginSection": 4355, "offsetInEndSection": 4467, "text": "AUTHORS' CONCLUSIONS: There is currently no evidence that nicotine vaccines enhance long-term smoking cessation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22895958", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 837, "text": "3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21270788", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1149, "text": "Recently, the most advanced candidate vaccine, NicVAX, failed to meet the primary endpoint in two large phase III studies, although the correlation of higher abstinence rates in subjects with higher immunity to nicotine was observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22229310", "endSection": "abstract" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1655, "text": "CONCLUSION\n\nThe nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 289, "text": "First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 1480, "offsetInEndSection": 1642, "text": "CONCLUSION The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 271, "text": "First efficacy results of the nicotine vaccine 3'-AmNic-rEPA ( NicVAX ) showed that only a subgroup of the top 30 % antibody responders achieved higher abstinence rates than placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 289, "text": "First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1288, "text": "FINDINGS\nThere was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR)\u2009=\u20090.89, 95% confidence interval (CI)\u2009=\u20090.62-1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR\u2009=\u20091.03, 95% CI\u2009=\u20090.73-1.46).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1655, "text": "CONCLUSION\nThe nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24894625", "endSection": "abstract" } ] }, { "body": "Does natalizumab improve disease course of secondary progressive multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29545067", "http://www.ncbi.nlm.nih.gov/pubmed/28861122", "http://www.ncbi.nlm.nih.gov/pubmed/26788129" ], "ideal_answer": [ "No. Atalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component." ], "exact_answer": "no", "type": "yesno", "id": "5e48b1ddd14c9f295d000012", "snippets": [ { "offsetInBeginSection": 2879, "offsetInEndSection": 3108, "text": "INTERPRETATION: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29545067", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 700, "text": "In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26788129", "endSection": "abstract" }, { "offsetInBeginSection": 2885, "offsetInEndSection": 3114, "text": "INTERPRETATION\n\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29545067", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 867, "text": "Natalizumab did not achieve a statistically significant primary composite disability outcome in a trial of 887 patients with secondary progressive MS , but it did demonstrate a benefit on a prespecified component of the 9-Hole Peg Test . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28861122", "endSection": "abstract" }, { "offsetInBeginSection": 2885, "offsetInEndSection": 3114, "text": "INTERPRETATION\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29545067", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 700, "text": "In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26788129", "endSection": "abstract" }, { "offsetInBeginSection": 2851, "offsetInEndSection": 3064, "text": "Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29545067", "endSection": "abstract" } ] }, { "body": "Before 2019, what neurologic diseases are associated with the tau protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29441009", "http://www.ncbi.nlm.nih.gov/pubmed/27697018", "http://www.ncbi.nlm.nih.gov/pubmed/27995573", "http://www.ncbi.nlm.nih.gov/pubmed/20826658", "http://www.ncbi.nlm.nih.gov/pubmed/22009441", "http://www.ncbi.nlm.nih.gov/pubmed/20678581", "http://www.ncbi.nlm.nih.gov/pubmed/23552370" ], "ideal_answer": [ "Tau proteins are involved in the pathogenesis of multiple sclerosis and amyotrophic lateral sclerosis.", "Both Alzheimer's Disease and Multiple Sclerosis are associated with tau protein" ], "exact_answer": [ [ "Alzheimer's" ], [ "Multiple Sclerosis" ], [ "AML" ], [ "Pick's disease (PiD)" ], [ "parkinsonism linked to chromosome 17 (FTDP-17)" ], [ "progressive supranuclear palsy (PSP)" ], [ "frontotemporal dementia" ] ], "type": "list", "id": "5e3c841148dab47f26000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Abnormally hyperphosphorylated tau is the major protein constituent of neurofibrillary tangles (NFTs) in the brain of Alzheimer disease (AD) patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27995573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The hypothetical roles of arsenic in multiple sclerosis by induction of inflammation and aggregation of tau protein: A commentary", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27697018", "endSection": "title" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 1665, "text": "his hypothesis may add a new dimension to the understanding of MS etiology and help to design novel therapeutic agents against potential targets that might be discovered. If this hypothesis proves to be true, tau phosphorylation inhibitors can be potential candidates for MS drug development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27697018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid \u03b2 (A\u03b2), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted human", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29441009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The amyloid-forming proteins tau, \u03b1B crystallin, and amyloid P protein are all found in lesions of multiple sclerosis (MS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23552370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Alzheimer's disease (AD), progressive supranuclear palsy (PSP), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and Pick's disease (PiD) are commonly known as tauopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009441", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 620, "text": "In Alzheimer's and Parkinson's diseases, there is a hyperphosphorylation of tau that leads to the intracellular accumulation of tau in the form of neurofibrillary tangles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20678581", "endSection": "abstract" } ] }, { "body": "What is the difference between Daptacel and Pentacel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19117896" ], "ideal_answer": [ "Pentacel is a combination vaccine equivalent to the combination of Daptacel, IPOL and ActHIB vaccines." ], "type": "summary", "id": "5e7f6138835f4e477700001b", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 582, "text": "Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP(5) dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117896", "endSection": "abstract" } ] }, { "body": "AhR ligands are attractive drug targets for pharmaceutical development due to their induction of Cyp1a1, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17327465", "http://www.ncbi.nlm.nih.gov/pubmed/28944315" ], "ideal_answer": [ "Yes, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines." ], "exact_answer": "yes", "type": "yesno", "id": "5e52c9266d0a27794100004e", "snippets": [ { "offsetInBeginSection": 1054, "offsetInEndSection": 1323, "text": " Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines. We also found no evidence that short-term treatment with RMAhRLs produce \"dioxin-like toxicity\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944315", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 361, "text": "However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944315", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1227, "text": "Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944315", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1243, "text": "Based on our review of the data , there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944315", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 365, "text": "However , recent discoveries of new AhR ligands with potential therapeutic applications have been reported , inviting reconsideration of this policy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944315", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1228, "text": "Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944315", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 362, "text": "However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944315", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1329, "text": "Combining in vivo and in vitro findings, we identified nine AhR agonists, six of which are marketed therapeutics and have been approved by the U.S. Food and Drug Administration, including leflunomide, flutamide, and nimodipine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17327465", "endSection": "abstract" } ] }, { "body": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21266479", "http://www.ncbi.nlm.nih.gov/pubmed/19410542", "http://www.ncbi.nlm.nih.gov/pubmed/25813039", "http://www.ncbi.nlm.nih.gov/pubmed/22122340", "http://www.ncbi.nlm.nih.gov/pubmed/18268003" ], "ideal_answer": [ "H2A.Z probably helps RSC in keeping the gene nucleosome-free.", "H2A.Z probably helps RSC in keeping the gene nucleosome-fre", "Yes, the chromatin remodeling complex, RSC, uses H2A. Z nucleosomes to remodel chromatin.", "yes, Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation.", "H2A.Z probably helps RSC in keeping the gene nucleosome-fre Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation." ], "exact_answer": "yes", "type": "yesno", "id": "5d385f717bc3fee31f00001a", "snippets": [ { "offsetInBeginSection": 646, "offsetInEndSection": 927, "text": "In contrast, the upstream nucleosome which covers the TATA box under repressed conditions is shifted approximately 50 bp further upstream by the ATP-dependent chromatin remodeler RSC upon activation. It is marked with the histone variant H2A.Z and H4K16 acetylation in active state", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18268003", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 576, "text": "In RSC-depleted cells, NFRs shrink such that the average positions of flanking nucleosomes move toward predicted sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19410542", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 819, "text": "In contrast, H2A.Z deposition is dispensable for nucleosome positioning. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19410542", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 723, "text": "Emerging lines of evidence indicate that histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB) response as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22122340", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 865, "text": "H2A.Z probably helps RSC in keeping the gene nucleosome-fre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21266479", "endSection": "abstract" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1092, "text": "Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25813039", "endSection": "abstract" } ] }, { "body": "List radioprotection agents.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29801788", "http://www.ncbi.nlm.nih.gov/pubmed/28581409", "http://www.ncbi.nlm.nih.gov/pubmed/29141565", "http://www.ncbi.nlm.nih.gov/pubmed/30360725", "http://www.ncbi.nlm.nih.gov/pubmed/30136132", "http://www.ncbi.nlm.nih.gov/pubmed/23796837", "http://www.ncbi.nlm.nih.gov/pubmed/29671693", "http://www.ncbi.nlm.nih.gov/pubmed/25400428", "http://www.ncbi.nlm.nih.gov/pubmed/27389300" ], "ideal_answer": [ "Amifostine\nCAPE\nMelanin\nMelatonin\nMetformin\nTea polyphenols \nalpha-2-macroglobulin" ], "exact_answer": [ [ "amifostine" ], [ "CAPE" ], [ "Melanin" ], [ "Melatonin" ], [ "Metformin" ], [ "Tea polyphenols" ], [ "alpha-2-macroglobulin" ] ], "type": "list", "id": "5e4703d13f54159529000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Amifostine is the first FDA approved cytoprotective and chemoprotective agent in the treatment of cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23796837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "A combination of resveratrol and 3,3'-diindolylmethane, a potent radioprotector.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29671693", "endSection": "title" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1580, "text": "CAPE was found to act both as radioprotector and radiosensitizer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29141565", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 330, "text": "Melanin, a naturally occurring, ubiquitous pigment, has been shown to confer radioresistance, acting as a potential radioprotective agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29801788", "endSection": "abstract" }, { "offsetInBeginSection": 2156, "offsetInEndSection": 2253, "text": "we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30136132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360725", "endSection": "title" }, { "offsetInBeginSection": 104, "offsetInEndSection": 198, "text": " Tea polyphenols (TPs) have been shown to reduce radiation-induced damage in multiple studies,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27389300", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 978, "text": "Recent studies have shown that alpha-2-macroglobulin (\u03b12M) possesses radioprotective effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25400428", "endSection": "abstract" } ] }, { "body": "What is the effect of Satb1 knock-out in mice?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30024617", "http://www.ncbi.nlm.nih.gov/pubmed/15851481", "http://www.ncbi.nlm.nih.gov/pubmed/29388727" ], "ideal_answer": [ "inhibited cell viability and migration", "While T cell growth in vitro, Satb1 knockdown was found to be effective in vivo by inhibiting T cell proliferation and activating apoptosis in a subset of T cells", "knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis.", "SATB1 is essential for maintaining TCR responsiveness during the induction and effector phases and may provide a novel therapeutic target for T cell-mediated autoimmune diseases. knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis.", "Knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis." ], "exact_answer": [ "apoptosis" ], "type": "factoid", "id": "5d36b8a37bc3fee31f000009", "snippets": [ { "offsetInBeginSection": 1479, "offsetInEndSection": 1694, "text": "ur studies indicate that both nuclear matrix association and DNA binding are required for optimal SATB1-mediated repression of the integrated MMTV promoter and may allow insulation from cellular regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15851481", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 404, "text": " T cells from SATB1 conditional knockout (SATB1cKO) mice, in which the Satb1 gene is deleted from hematopoietic cells, impair phosphorylation of signaling molecules in response to T cell receptor (TCR) crosslinking", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29388727", "endSection": "abstract" }, { "offsetInBeginSection": 1602, "offsetInEndSection": 1780, "text": "SATB1 is essential for maintaining TCR responsiveness during the induction and effector phases and may provide a novel therapeutic target for T cell-mediated autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29388727", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 876, "text": "knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30024617", "endSection": "abstract" } ] }, { "body": "Has ZP-PTH been tested in a phase II clinical trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20183917" ], "ideal_answer": [ "Yes, ZP-PTH was successfully tested in a phase II clinical trial for the treatment of post-menopausal women with osteoporosis." ], "exact_answer": "yes", "type": "yesno", "id": "5e7f69d2835f4e4777000021", "snippets": [ { "offsetInBeginSection": 1827, "offsetInEndSection": 1952, "text": "This system was successfully tested in a Phase 2 clinical trial for the treatment of post-menopausal women with osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20183917", "endSection": "abstract" } ] }, { "body": "PH motifs in which genes endow breast cancer growth?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26928551", "http://www.ncbi.nlm.nih.gov/pubmed/26600192" ], "ideal_answer": [ "Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Signal-binding motifs in PAR1&2 are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes." ], "exact_answer": [ [ "PAR1" ], [ "PAR2" ] ], "type": "list", "id": "5e52900d6d0a277941000041", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1080, "text": "Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26600192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 47, "text": "PH motifs in PAR1&2 endow breast cancer growth.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26600192", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 239, "text": "Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26600192", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 811, "text": "The identification and characterization of signal pleckstrin homology (PH)-domain-binding motifs established critical sites for breast cancer growth in PAR1&2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26928551", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 240, "text": "Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26600192", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 812, "text": "The identification and characterization of signal pleckstrin homology (PH)-domain-binding motifs established critical sites for breast cancer growth in PAR1&2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26928551", "endSection": "abstract" } ] }, { "body": "What is herd immunity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29254557", "http://www.ncbi.nlm.nih.gov/pubmed/29429063", "http://www.ncbi.nlm.nih.gov/pubmed/29047019", "http://www.ncbi.nlm.nih.gov/pubmed/28557577" ], "ideal_answer": [ "Vaccines are very effective in providing individual and community (herd) immunity against a range of diseases.\nWe argue that individuals who have access to vaccines and for whom vaccination is not medically contraindicated have a moral obligation to contribute to the realisation of herd immunity by being vaccinated." ], "type": "summary", "id": "5e6e9348c6a8763d23000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Vaccines are very effective in providing individual and community (herd) immunity against a range of diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "We argue that individuals who have access to vaccines and for whom vaccination is not medically contraindicated have a moral obligation to contribute to the realisation of herd immunity by being vaccinated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29429063", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 170, "text": "Delays in vaccination can stymie the development of herd immunity, and a large proportion of children in the U.S. are known not to receive vaccines on time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29254557", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 862, "text": "is to drive population control of disease beyond those who are vaccinated (i.e. through herd immunity). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28557577", "endSection": "abstract" } ] }, { "body": "Are multipotent adult progenitor cells effective for treatment of stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28320635" ], "ideal_answer": [ "No. There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90. Further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned." ], "exact_answer": "no", "type": "yesno", "id": "5e48b9abd14c9f295d000015", "snippets": [ { "offsetInBeginSection": 2943, "offsetInEndSection": 3520, "text": "There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1\u00b708 [95% CI 0\u00b755-2\u00b709], p=0\u00b783).INTERPRETATION: Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320635", "endSection": "abstract" }, { "offsetInBeginSection": 3125, "offsetInEndSection": 3262, "text": "INTERPRETATION\n\nAdministration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320635", "endSection": "abstract" }, { "offsetInBeginSection": 3263, "offsetInEndSection": 3526, "text": "Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320635", "endSection": "abstract" }, { "offsetInBeginSection": 3119, "offsetInEndSection": 3255, "text": "INTERPRETATION Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320635", "endSection": "abstract" }, { "offsetInBeginSection": 3262, "offsetInEndSection": 3526, "text": "Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320635", "endSection": "abstract" }, { "offsetInBeginSection": 3213, "offsetInEndSection": 3476, "text": "Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320635", "endSection": "abstract" } ] }, { "body": "List the stages/types of Multiple Sclerosis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28349074", "http://www.ncbi.nlm.nih.gov/pubmed/29465579", "http://www.ncbi.nlm.nih.gov/pubmed/29968175" ], "ideal_answer": [ "Multiple sclerosis presents with different phenotypes, most commonly a relapsing-remitting course and, less frequently, a progressive accumulation of disability from disease onset (primary progressive multiple sclerosis). The majority of people with relapsing-remitting multiple sclerosis, after a variable time, switch to a stage characterised by gradual neurological worsening known as secondary progressive multiple sclerosis.", "Multiple Sclerosis (MS) is divided into three stages: primary progressive, relapsing-remitting, relapping-Remitting MS, and secondary progressive MS.", "Multiple Sclerosis can be classified into four different stages (A to C), with different types of neurodegenerative disorders such as primary, chronic, relapsing-remitting and progressive forms.", "Multiple Sclerosis (MS) is a multisystem disorder, which can be classified into primary progressive, relapsing-remitting, relapping-remoting and non-progressive stages." ], "exact_answer": [ [ "Primary Progressive" ], [ "Relapsing-Remitting" ], [ "Secondary Progressive" ] ], "type": "list", "id": "5e52c5166d0a27794100004d", "snippets": [ { "offsetInBeginSection": 334, "offsetInEndSection": 508, "text": " MS and hospitalized were included and analyzed after which they were divided into the primary progressive MS A and B groups, the relapsing-remitting MS (RRMS) C and D groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29465579", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 607, "text": "Multiple sclerosis presents with different phenotypes, most commonly a relapsing-remitting course and, less frequently, a progressive accumulation of disability from disease onset (primary progressive multiple sclerosis). The majority of people with relapsing-remitting multiple sclerosis, after a variable time, switch to a stage characterised by gradual neurological worsening known as secondary progressive multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29968175", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 466, "text": " relapsing-remitting MS, primary and secondary progressive MS) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28349074", "endSection": "abstract" } ] }, { "body": "What is known about Opicinumab for multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29779852", "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "http://www.ncbi.nlm.nih.gov/pubmed/28885860" ], "ideal_answer": [ "Opicinumab is a new Anti lingo 1 monoclonal antibody that is tested in relapsing remitting multiple sclerosis. The anti-LINGO-1 trial showed that the drug is safe and tolerable. A future phase II trial will provide more insights regarding the compound." ], "type": "summary", "id": "5e48ab8dd14c9f295d000010", "snippets": [ { "offsetInBeginSection": 100, "offsetInEndSection": 508, "text": "Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod\u2026); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin\u2026). Nevertheless, despite recent promising positive clinical trials, new methodological approaches for therapeutic protocols with adaptable outcomes to assess progression are still needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29779852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Anti lingo 1 (opicinumab) a new monoclonal antibody tested in relapsing remitting multiple sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28885860", "endSection": "title" }, { "offsetInBeginSection": 709, "offsetInEndSection": 873, "text": "Anti-LINGO-1 (opicinumab) is the first investigational product that achieved phase I trial with the aim of remyelination and axonal protection and/or repair in MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28885860", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1152, "text": " The anti-LINGO-1 trial showed that the drug is safe and tolerable. A future phase II trial will provide more insights regarding the compound.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28885860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "BACKGROUND\n\nOpicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 374, "text": "We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 826, "text": "Participants (aged 18-58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 373, "text": "We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 374, "text": "We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "BACKGROUND\nOpicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" }, { "offsetInBeginSection": 695, "offsetInEndSection": 859, "text": "Anti-LINGO-1 (opicinumab) is the first investigational product that achieved phase I trial with the aim of remyelination and axonal protection and/or repair in MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28885860", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 362, "text": "We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285147", "endSection": "abstract" } ] }, { "body": "What is the target of Inebilizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30915717", "http://www.ncbi.nlm.nih.gov/pubmed/29512131", "http://www.ncbi.nlm.nih.gov/pubmed/29143550", "http://www.ncbi.nlm.nih.gov/pubmed/29956883", "http://www.ncbi.nlm.nih.gov/pubmed/28910968", "http://www.ncbi.nlm.nih.gov/pubmed/27886126", "http://www.ncbi.nlm.nih.gov/pubmed/29447988", "http://www.ncbi.nlm.nih.gov/pubmed/31495497" ], "ideal_answer": [ "Inebilizumab is an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in multiple sclerosis and neuromyelitis optica." ], "exact_answer": [ "CD19" ], "type": "factoid", "id": "5e47681b35b8f0833c000006", "snippets": [ { "offsetInBeginSection": 443, "offsetInEndSection": 627, "text": "CONTENT: Although CD19-targeted agents (blinatumomab or inebilizumab) are not associated with an increased risk of infection, they may cause IgG hypogammaglobulinaemia and neutropenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29447988", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 928, "text": "In this respect, several B cell-targeted therapies emerged, including anti-CD20 antibodies (rituximab, ocrelizumab, and ofatumumab), anti-CD19 antibody (inebilizumab), and agents targeting the BAFF/APRIL signaling pathway (atacicept, belimumab, and LY2127399). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29512131", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1346, "text": "Patients with a high PC signature at baseline showed greater improvement in the MRSS (mean \u00b1 SD change 35 \u00b1 16%; P = 6.30 \u00d7 10-4 ) following anti-CD19 treatment with inebilizumab (MEDI-551) than did patients with a low PC signature at baseline (mean \u00b1 SD change 8 \u00b1 12%; P = 0.104).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29956883", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 1093, "text": "In NMO, though there have yet to be any approved monoclonal antibodies, rituximab, anti-complement C5 (eculizumab), anti-IL-6 receptor (tocilizumab), anti-CD19 (inebilizumab) and non-pathogenic anti-aquaporin 4 (aquaporumab) have been suggested to be effective, and some of these are now under clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28910968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143550", "endSection": "title" }, { "offsetInBeginSection": 87, "offsetInEndSection": 156, "text": "Inebilizumab (formerly MEDI-551) binds to and depletes CD19+ B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27886126", "endSection": "title" }, { "offsetInBeginSection": 442, "offsetInEndSection": 626, "text": "Inebilizumab (MEDI-551), an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in MS and neuromyelitis optica.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27886126", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 349, "text": "We aimed to assess the efficacy and safety of inebilizumab, an anti-CD19, B cell-depleting antibody, in reducing the risk of attacks and disability in NMOSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31495497", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 156, "text": "Inebilizumab (formerly MEDI-551) binds to and depletes CD19 + B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "A multicenter phase I study of inebilizumab, a humanized anti-CD19 monoclonal antibody, in Japanese patients with relapsed or refractory B-cell lymphoma and multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30915717", "endSection": "title" }, { "offsetInBeginSection": 449, "offsetInEndSection": 633, "text": "CONTENT\n\nAlthough CD19-targeted agents (blinatumomab or inebilizumab) are not associated with an increased risk of infection, they may cause IgG hypogammaglobulinaemia and neutropenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29447988", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 927, "text": "In this respect, several B cell-targeted therapies emerged, including anti-CD20 antibodies (rituximab, ocrelizumab, and ofatumumab), anti-CD19 antibody (inebilizumab), and agents targeting the BAFF/APRIL signaling pathway (atacicept, belimumab, and LY2127399).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29512131", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 952, "text": "In this respect , several B cell-targeted therapies emerged , including anti-CD20 antibodies ( rituximab , ocrelizumab , and ofatumumab) , anti-CD19 antibody ( inebilizumab) , and agents targeting the BAFF/APRIL signaling pathway ( atacicept , belimumab , and LY2127399) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29512131", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 1127, "text": "In NMO , though there have yet to be any approved monoclonal antibodies , rituximab , anti-complement C5 ( eculizumab) , anti-IL-6 receptor ( tocilizumab) , anti-CD19 ( inebilizumab ) and non-pathogenic anti-aquaporin 4 ( aquaporumab ) have been suggested to be effective , and some of these are now under clinical trials . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28910968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Safety and tolerability of inebilizumab ( MEDI-551) , an anti-CD19 monoclonal antibody , in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised , placebo-controlled , escalating intravenous and subcutaneous dose study .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143550", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "A multicenter phase I study of inebilizumab , a humanized anti-CD19 monoclonal antibody , in Japanese patients with relapsed or refractory B-cell lymphoma and multiple myeloma .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30915717", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 347, "text": "We aimed to assess the efficacy and safety of inebilizumab , an anti-CD19 , B cell-depleting antibody , in reducing the risk of attacks and disability in NMOSD .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31495497", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 349, "text": "We aimed to assess the efficacy and safety of inebilizumab, an anti-CD19, B cell-depleting antibody, in reducing the risk of attacks and disability in NMOSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31495497", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 156, "text": "Inebilizumab (formerly MEDI-551) binds to and depletes CD19+ B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143550", "endSection": "abstract" } ] }, { "body": "Is eculizumab effective for Guillain-Barr\u00e9 syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29685815", "http://www.ncbi.nlm.nih.gov/pubmed/31171755", "http://www.ncbi.nlm.nih.gov/pubmed/27801990" ], "ideal_answer": [ "In a clinical trial eculizumab did not achieve primary outcome for Guillain-Barre syndrome. However, because this was a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials." ], "type": "summary", "id": "5e48af7ad14c9f295d000011", "snippets": [ { "offsetInBeginSection": 2174, "offsetInEndSection": 2456, "text": "INTERPRETATION: The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29685815", "endSection": "abstract" }, { "offsetInBeginSection": 1584, "offsetInEndSection": 2018, "text": "At week 4, the proportion of the patients able to walk independently (functional grade \u22642) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29685815", "endSection": "abstract" }, { "offsetInBeginSection": 1005, "offsetInEndSection": 1181, "text": "For the primary efficacy outcome at 4 weeks after recruitment, two of two placebo- and two of five eculizumab-treated subjects had improved by one or more grades on the GBS DS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27801990", "endSection": "abstract" }, { "offsetInBeginSection": 2268, "offsetInEndSection": 2462, "text": "However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29685815", "endSection": "abstract" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1775, "text": "At week 4, the proportion of the patients able to walk independently (functional grade \u22642) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29685815", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 412, "text": "A recent Japanese randomized controlled trial with eculizumab, a monoclonal antibody against the complement C5, indicated that eculizumab might improve the outcomes of GBS patients at six months from onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171755", "endSection": "abstract" }, { "offsetInBeginSection": 2218, "offsetInEndSection": 2412, "text": "However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29685815", "endSection": "abstract" } ] }, { "body": "List Mcl-1 inhibitors.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30139826", "http://www.ncbi.nlm.nih.gov/pubmed/29580266", "http://www.ncbi.nlm.nih.gov/pubmed/30017199", "http://www.ncbi.nlm.nih.gov/pubmed/30185782", "http://www.ncbi.nlm.nih.gov/pubmed/30185825" ], "ideal_answer": [ "A-1210477\nS63845" ], "exact_answer": [ [ "A-1210477" ], [ "S63845" ] ], "type": "list", "id": "5e6e8897c6a8763d23000003", "snippets": [ { "offsetInBeginSection": 238, "offsetInEndSection": 363, "text": "The recent description of S63845 as the first specific and potent MCL-1 inhibitor represents an important therapeutic advance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30185825", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 550, "text": " We tested the efficacy of the BH3 mimetic combination of A-1210477 (an MCL-1 inhibitor)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30185782", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 192, "text": "a highly specific MCL-1 inhibitor, S63845,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30139826", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 815, "text": "Mcl-1 inhibitor S63845", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30017199", "endSection": "abstract" }, { "offsetInBeginSection": 664, "offsetInEndSection": 702, "text": "A-1210477, a selective MCL-1 inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29580266", "endSection": "abstract" } ] }, { "body": "Autophagy is the process where a virus obtains nutrients from it's host, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29022289", "http://www.ncbi.nlm.nih.gov/pubmed/22475795", "http://www.ncbi.nlm.nih.gov/pubmed/24779013", "http://www.ncbi.nlm.nih.gov/pubmed/30544615", "http://www.ncbi.nlm.nih.gov/pubmed/28884441", "http://www.ncbi.nlm.nih.gov/pubmed/28889353", "http://www.ncbi.nlm.nih.gov/pubmed/31803515", "http://www.ncbi.nlm.nih.gov/pubmed/24914338" ], "ideal_answer": [ "No, autophagy is important in cellular homeostasis for the cell survival mechanism and is involved apoptosis.", "Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles.", "Autophagy is important in cellular homeostasis for the cell survival mechanism." ], "exact_answer": "no", "type": "yesno", "id": "5e3d8edf48dab47f26000003", "snippets": [ { "offsetInBeginSection": 392, "offsetInEndSection": 537, "text": "In this study, we demonstrate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Autophagy is important in cellular homeostasis for the cell survival mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28889353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29022289", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 457, "text": "Autophagy-related genes (ATGs) regulate the autophagy and also control the crosstalk with autophagy-associated cell death and apoptosis in some condition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28889353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30544615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24914338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Autophagy is a self-eating process, in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31803515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24914338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30544615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Autophagy is a homeostatic process involved in the turnover or elimination of cytoplasmic components, damaged organelles, and protein aggregates via a lysosomal degradation mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475795", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 363, "text": "Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779013", "endSection": "abstract" } ] }, { "body": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26080409" ], "ideal_answer": [ "MPE-seq (methidiumpropyl-EDTA sequencing) is a new method for the genome-wide characterization of chromatin that involves the digestion of nuclei with MPE-Fe(II) followed by massively parallel sequencing of the whole genome. Like micrococcal nuclease (MNase), MNase preferentially cleaves the linker DNA between nucleosomes. However, there are differences in the cleavage of nuclear chromatin by MP e-seq relative to MNase. Moreover, unlike MNase, MPe-seq cleaves nuclear DNA", "Methidiumpropyl-EDTA sequencing (MPE-seq) is a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq unlike MNase-seq cleaves nuclear DNA with little sequence bias and thus provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias.", "digestion of nuclei withmpe-fe(ii)", "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias.", "Methidiumpropyl-edta sequencing is a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withmpe-fe (ii) followed by massively parallel sequencing. Mpe-seq provides a unique and straightforward means for theome-wide analysis of chromat structure with minimal dna sequence bias.", "The methidiumpropyl-EDTA sequencing (MPE-seq) method uses a GpC methyltransferase (M. CviPI) and next generation sequencing to generate a high resolution footprint of nucleosome structure using less than 1 million cells while retaining endogenous DNA fragments from the same DNA strand.", " methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias.", " methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias.", "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing.", "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. ", "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias." ], "type": "summary", "id": "5d3858a97bc3fee31f000018", "snippets": [ { "offsetInBeginSection": 133, "offsetInEndSection": 331, "text": "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1601, "text": "MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26080409", "endSection": "abstract" } ] }, { "body": "Name two rotavirus vaccines.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29436336" ], "ideal_answer": [ "Two rotavirus vaccines licensed for global use are RotaTeq and Rotarix." ], "exact_answer": [ [ "Rotateq" ], [ "Rotarix" ] ], "type": "list", "id": "5e7659db835f4e4777000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Two rotavirus vaccines, RotaTeq and Rotarix, are licensed for global use; however, the protection they confer to unvaccinated individuals through indirect effects remains unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29436336", "endSection": "abstract" } ] }, { "body": "Does CXorf21 escape X chromosome inactivation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17504899", "http://www.ncbi.nlm.nih.gov/pubmed/24596594", "http://www.ncbi.nlm.nih.gov/pubmed/27729837", "http://www.ncbi.nlm.nih.gov/pubmed/17347996" ], "ideal_answer": [ "CXORF21 belongs to a set of X-linked differentially expressed genes that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function.", "Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function.", "yes, Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function." ], "exact_answer": "yes", "type": "yesno", "id": "5d387a51a1e159510500000e", "snippets": [ { "offsetInBeginSection": 932, "offsetInEndSection": 1095, "text": "This revealed a 637-kb tandem duplication that in addition to DAX1 includes the four MAGEB genes, the hypothetical gene CXorf21, GK, and part of the MAP3K7IP3 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17504899", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1220, "text": "Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24596594", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 885, "text": " For this, we selected five SNPs (rs1801274 in FCGR2A and rs2286672 in PLD2, rs887369 in CXorf21, rs9782955 in LYST, and rs3794060 in NADSYN1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729837", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1596, "text": "Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17347996", "endSection": "abstract" } ] }, { "body": "Which programming language has been used for implementing GWAR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28108451" ], "ideal_answer": [ "Stata" ], "exact_answer": [ "Stata" ], "type": "factoid", "id": "5e50123e6d0a277941000036", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 1597, "text": "In the context of genome-wide association studies (GWAS), there is a variety of statistical techniques in order to conduct the analysis, but, in most cases, the underlying genetic model is usually unknown. Under these circumstances, the classical Cochran-Armitage trend test (CATT) is suboptimal. Robust procedures that maximize the power and preserve the nominal type I error rate are preferable. Moreover, performing a meta-analysis using robust procedures is of great interest and has never been addressed in the past. The primary goal of this work is to implement several robust methods for analysis and meta-analysis in the statistical package Stata and subsequently to make the software available to the scientific community.Results: The CATT under a recessive, additive and dominant model of inheritance as well as robust methods based on the Maximum Efficiency Robust Test statistic, the MAX statistic and the MIN2 were implemented in Stata. Concerning MAX and MIN2, we calculated their asymptotic null distributions relying on numerical integration resulting in a great gain in computational time without losing accuracy. All the aforementioned approaches were employed in a fixed or a random effects meta-analysis setting using summary data with weights equal to the reciprocal of the combined cases and controls. Overall, this is the first complete effort to implement procedures for analysis and meta-analysis in GWAS using Stata.Availability and Implementation: A Stata program and a web-server are freely available for academic users at http://www.compgen.org/tools/GWAR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28108451", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1601, "text": "Availability and Implementation\n\nA Stata program and a web-server are freely available for academic users at http://www.compgen.org/tools/GWAR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28108451", "endSection": "abstract" } ] }, { "body": "Describe f-scLVM", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29115968" ], "ideal_answer": [ "Single-cell RNA-sequencing (scRNA-seq) allows studying heterogeneity in gene expression in large cell populations. Such heterogeneity can arise due to technical or biological factors, making decomposing sources of variation difficult. F-scLVM (factorial single-cell latent variable model) is a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity. The model jointly estimates the relevance of individual factors, refines gene set annotations, and infers factors without annotation. F-scLVM robustly decomposes scRNA-seq datasets into interpretable components, thereby facilitating the identification of novel subpopulations.", "f-scLVM (factorial single-cell latent variable model) is a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity. It jointly estimates the relevance of individual factors, refines gene set annotations, and infers factors without annotation. In applications to multiple scRNA-seq datasets, f-SCLVM robustly decomposes scRNA -seq datasets into interpretable components, thereby facilitating the identification of novel subpopulations." ], "type": "summary", "id": "5e52937c6d0a277941000042", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "f-scLVM: scalable and versatile factor analysis for single-cell RNA-seq.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115968", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 788, "text": "Single-cell RNA-sequencing (scRNA-seq) allows studying heterogeneity in gene expression in large cell populations. Such heterogeneity can arise due to technical or biological factors, making decomposing sources of variation difficult. We here describe f-scLVM (factorial single-cell latent variable model), a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity. Our model jointly estimates the relevance of individual factors, refines gene set annotations, and infers factors without annotation. In applications to multiple scRNA-seq datasets, we find that f-scLVM robustly decomposes scRNA-seq datasets into interpretable components, thereby facilitating the identification of novel subpopulations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115968", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 450, "text": "We here describe f-scLVM (factorial single-cell latent variable model), a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115968", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 456, "text": "We here describe f-scLVM ( factorial single-cell latent variable model) , a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "f-scLVM: scalable and versatile factor analysis for single-cell RNA-seq", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115968", "endSection": "title" }, { "offsetInBeginSection": 235, "offsetInEndSection": 451, "text": "We here describe f-scLVM (factorial single-cell latent variable model), a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115968", "endSection": "abstract" } ] }, { "body": "Does promoter shape vary across populations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28191888" ], "ideal_answer": [ "Yes. Promoter shape varies across populations and affects promoter evolution and expression noise. This is accompanied by differences in the expression levels of different genes, which may reflect differences in their regulatory mechanisms.", "Yes. Promoter shape varies across populations and affects promoter evolution and expression noise.", "Yes. Promoter shape varies across populations and affects promoter evolution and expression noise. In some populations, promoter shape is more or less consistent across populations, while in other populations it varies little." ], "exact_answer": "yes", "type": "yesno", "id": "5e52ab626d0a277941000046", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Promoter shape varies across populations and affects promoter evolution and expression noise.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28191888", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1162, "text": "Animal promoters initiate transcription either at precise positions (narrow promoters) or dispersed regions (broad promoters), a distinction referred to as promoter shape. Although highly conserved, the functional properties of promoters with different shapes and the genetic basis of their evolution remain unclear. Here we used natural genetic variation across a panel of 81 Drosophila lines to measure changes in transcriptional start site (TSS) usage, identifying thousands of genetic variants affecting transcript levels (strength) or the distribution of TSSs within a promoter (shape). Our results identify promoter shape as a molecular trait that can evolve independently of promoter strength. Broad promoters typically harbor shape-associated variants, with signatures of adaptive selection. Single-cell measurements demonstrate that variants modulating promoter shape often increase expression noise, whereas heteroallelic interactions with other promoter variants alleviate these effects. These results uncover new functional properties of natural promoters and suggest the minimization of expression noise as an important factor in promoter evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28191888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Promoter shape varies across populations and affects promoter evolution and expression noise", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28191888", "endSection": "title" } ] }, { "body": "How large is a lncRNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27098144", "http://www.ncbi.nlm.nih.gov/pubmed/26308238", "http://www.ncbi.nlm.nih.gov/pubmed/27933111", "http://www.ncbi.nlm.nih.gov/pubmed/27510368" ], "ideal_answer": [ "lncRNAs are defined as RNA transcripts longer than 200 nucleotides that are not transcribed into proteins" ], "exact_answer": [ ">200 nucleotides" ], "type": "factoid", "id": "5e6e8f92c6a8763d23000004", "snippets": [ { "offsetInBeginSection": 158, "offsetInEndSection": 264, "text": " lncRNAs are defined as RNA transcripts longer than 200 nucleotides that are not transcribed into proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27510368", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 765, "text": "lncRNAs are the nonprotein coding RNAs that have a size longer than 200 nucleotides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27098144", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 115, "text": " Long noncoding RNAs (lncRNAs) are more than 200 nucleotides in length and lack transcriptional ability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27933111", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 452, "text": " long noncoding RNA (lncRNA, >200 nucleotides)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26308238", "endSection": "abstract" } ] }, { "body": "What is MLE4901?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28385352" ], "ideal_answer": [ "MLE4901 is an oral neurikinin 3 receptor antagonist that has been shown to safely and effectively relieve hot flush symptoms in menopausal women without the need for oestrogen exposure." ], "type": "summary", "id": "5e543704b761aafe09000001", "snippets": [ { "offsetInBeginSection": 333, "offsetInEndSection": 532, "text": "This phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28385352", "endSection": "abstract" }, { "offsetInBeginSection": 2272, "offsetInEndSection": 2457, "text": "Treatment with a neurokinin 3 receptor antagonist (MLE4901) could be practice changing as it safely and effectively relieves hot flush symptoms without the need for oestrogen exposure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28385352", "endSection": "abstract" } ] }, { "body": "What is the drug chloroquine or hydroxychloroquine used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28259568", "http://www.ncbi.nlm.nih.gov/pubmed/28862574", "http://www.ncbi.nlm.nih.gov/pubmed/28823509", "http://www.ncbi.nlm.nih.gov/pubmed/30308208", "http://www.ncbi.nlm.nih.gov/pubmed/16115318" ], "ideal_answer": [ "Chloroquine (CQ) has been used for decades as the primary chemotherapeutic drug for the treatment of malaria.\nHydroxychloroquine (HCQ), a 4-aminoquinolone antimalarial, is regarded as the oral therapy of choice for cutaneous and systemic lupus erythematosus (SLE). It is also licensed for rheumatoid arthritis (RA).\nChloroquine is a potent inhibitor of SARS coronavirus infection and spread." ], "exact_answer": [ [ "Malaria" ], [ "Systemic lupus erythematosus" ], [ "Rheumatoid arthritis" ], [ "Coronavirus infection" ] ], "type": "list", "id": "5e80caeb835f4e477700002b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Chloroquine (CQ) has been used for decades as the primary chemotherapeutic drug for the treatment of malaria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Historically chloroquine was used to treat the most deadly form of malaria, caused by the parasite Plasmodium falciparum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28823509", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 512, "text": "we investigated how chloroquine (CQ), a commonly employed disease-modifying antirheumatic drug,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259568", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 216, "text": "Hydroxychloroquine (HCQ), a 4-aminoquinolone antimalarial, is regarded as the oral therapy of choice for cutaneous and systemic lupus erythematosus (SLE). It is also licensed for rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28862574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16115318", "endSection": "title" } ] }, { "body": "Does xaliproden improve prognosis of amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22513921", "http://www.ncbi.nlm.nih.gov/pubmed/15204012", "http://www.ncbi.nlm.nih.gov/pubmed/28072907", "http://www.ncbi.nlm.nih.gov/pubmed/15204011" ], "ideal_answer": [ "No. There is not sufficient high quality evidence that xaliproden significantly improves prognosis of amyotrophic lateral sclerosis patients." ], "exact_answer": "no", "type": "yesno", "id": "5e4b5ef36d0a27794100001f", "snippets": [ { "offsetInBeginSection": 1275, "offsetInEndSection": 1761, "text": "Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28072907", "endSection": "abstract" }, { "offsetInBeginSection": 1649, "offsetInEndSection": 2062, "text": "The medications comprised vitamin E, baclofen, riluzole, L-threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22513921", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 981, "text": ". The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204011", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1349, "text": "These results support the use of a staging process to select suitable patients for phase II studies, and suggest that xaliproden may have potential effects in ALS and deserve further study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204011", "endSection": "abstract" }, { "offsetInBeginSection": 1627, "offsetInEndSection": 1857, "text": "An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204012", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 981, "text": "The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204011", "endSection": "abstract" }, { "offsetInBeginSection": 1627, "offsetInEndSection": 1702, "text": "An effect of xaliproden on functional parameters, especially VC, was noted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204012", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1350, "text": "These results support the use of a staging process to select suitable patients for phase II studies, and suggest that xaliproden may have potential effects in ALS and deserve further study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204011", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 982, "text": "The six months intent-to-treat analysis showed no statistically significant effect but a trend in favour of 2 mg xaliproden compared to placebo for reduction in the rate of deterioration of FVC, limbs functional score, and manual muscle testing score (MMT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204011", "endSection": "abstract" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 1857, "text": "Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15204012", "endSection": "abstract" } ] }, { "body": "What is Telangiectasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22810475", "http://www.ncbi.nlm.nih.gov/pubmed/28803159", "http://www.ncbi.nlm.nih.gov/pubmed/22170760", "http://www.ncbi.nlm.nih.gov/pubmed/11316039" ], "ideal_answer": [ "Telangiectasia (macroscopically visible dilated skin vessels)", "Telangiectasias are small focal red macules and papules created by abnormally prominent capillaries, venules, and arterioles", "Telangiectasias are prominent small vessels (venules, capillaries or arterioles) that are visible as small red-purple focal lesions in the skin and mucous membranes.", "Telangiectasias are small focal red macules and papules created by abnormally prominent capillaries, venules, and arterioles Telangiectasia (macroscopically visible dilated skin vessels)" ], "exact_answer": [ "prominent small vessels" ], "type": "factoid", "id": "5e3c686fb5b409ea53000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Telangiectasias are prominent small vessels (venules, capillaries or arterioles) that are visible as small red-purple focal lesions in the skin and mucous membranes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28803159", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 402, "text": "Telangiectasias are small focal red macules and papules created by abnormally prominent capillaries, venules, and arterioles ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22170760", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 321, "text": "Telangiectasia (macroscopically visible dilated skin vessels)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11316039", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 387, "text": "Hereditary hemorrhagic telangiectasia is a dominant disorder characterized by epistaxis, visceral arteriovenous malformations, and telangiectasias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810475", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 448, "text": "Telangiectasia (macroscopically visible dilated skin vessels) occurring primarily on the hands and face, are a prominent feature in scleroderma and are present in the majority of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11316039", "endSection": "abstract" } ] }, { "body": "Is cathepsin L active in endosomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26343556", "http://www.ncbi.nlm.nih.gov/pubmed/22238299", "http://www.ncbi.nlm.nih.gov/pubmed/26953343", "http://www.ncbi.nlm.nih.gov/pubmed/27733646" ], "ideal_answer": [ "yes,\nCathepsin L is found in the Late Endosome/Lysosome." ], "exact_answer": "yes", "type": "yesno", "id": "5e8101e3835f4e477700002e", "snippets": [ { "offsetInBeginSection": 42, "offsetInEndSection": 83, "text": "Cathepsin L in the Late Endosome/Lysosome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26953343", "endSection": "title" }, { "offsetInBeginSection": 235, "offsetInEndSection": 256, "text": "endosomal cathepsin L", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27733646", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 566, "text": "Immunofluorescence and immunoblotting investigations revealed the presence of cathepsin L in the nuclear compartment in addition to its expected endo-lysosomal localization in colorectal carcinoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26343556", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 332, "text": "cleavage by the endosomal/lysosomal protease cathepsin L", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22238299", "endSection": "abstract" } ] }, { "body": "Which tissues express the ACE2 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15221932", "http://www.ncbi.nlm.nih.gov/pubmed/24564768", "http://www.ncbi.nlm.nih.gov/pubmed/19014390", "http://www.ncbi.nlm.nih.gov/pubmed/19333547" ], "ideal_answer": [ "Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes" ], "exact_answer": [ [ "lung" ], [ "kidney" ], [ "heart" ], [ "pancreas" ] ], "type": "list", "id": "5e80e449835f4e477700002c", "snippets": [ { "offsetInBeginSection": 1409, "offsetInEndSection": 1487, "text": "in keeping with the variability of ACE2 expression we have observed previously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24564768", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 441, "text": "ACE2 has been identified in various tissues and is supposed to be a modulator of cardiovascular function. Decreases in ACE2 expression and activity have been reported in models of hypertension, heart failure, atherosclerosis, diabetic nephropathy and others. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19014390", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 814, "text": "ACE2 is expressed at high level in the primary target cells of SARS-CoV, namely pneumocytes and surface enterocytes of the small intestine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15221932", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1100, "text": "endothelial cells, which express ACE2 to a high level,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15221932", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1199, "text": "Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19333547", "endSection": "abstract" } ] }, { "body": "In which chromosome are transgenes inserted in the case of the LiPS-A3S line?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27898090" ], "ideal_answer": [ "Transgenesis of human pluripotent stem cells (hPSCs) can enable and empower a variety of studies in stem cell research, including lineage tracing and functional genetics studies. While in recent years much progress has been made in the development of tools for gene targeting, little attention has been given to the identification of sites in the human genome where transgenes can be inserted and reliably expressed. One cell line/clone, LiPS-A3, has an integration site in chromosome 15 maintaining robust expression without silencing. Different transgenes can be inserted therein rapidly and efficiently through recombinase-mediated cassette exchange (RMCE). The LiPS-A3 line can greatly facilitate the insertion of reporter and other genes in hPSCs. Targeting transgenes in the LiPS-A3S genomic locus can find broad applications in stem cell research and possibly cell and gene therapy.", "The LiPS-A3S line of human pluripotent stem cells is inserted via transgenesis from chromosome 15.", "The LiPS-A3S line of human pluripotent stem cells is inserted into chromosome 15.", "Human pluripotent stem cells (hPSCs) can enable and empower a variety of studies in stem cell research, including lineage tracing and functional genetics studies. In recent years much progress has been made in the development of tools for gene targeting, little attention has been given to the identification of sites in the human genome where transgenes can be inserted and reliably expressed. The LiPS-A3S line of chromosome 15 is one of the few genes with an integration site in chromosome 15." ], "exact_answer": [ "Chromosome 15" ], "type": "factoid", "id": "5e5286036d0a277941000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "LiPS-A3S, a human genomic site for robust expression of inserted transgenes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898090", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1265, "text": "Transgenesis of human pluripotent stem cells (hPSCs) can enable and empower a variety of studies in stem cell research, including lineage tracing and functional genetics studies. While in recent years much progress has been made in the development of tools for gene targeting, little attention has been given to the identification of sites in the human genome where transgenes can be inserted and reliably expressed. In order to find human genomic sites capable of supporting long-term and high-level transgene expression in hPSCs, we performed a lentiviral screen in human induced pluripotent stem cells (iPSCs). We isolated 40 iPSC clones each harboring a single vector copy and characterized the level of transgene expression afforded by each unique integration site. We selected one clone, LiPS-A3 with an integration site in chromosome 15 maintaining robust expression without silencing and demonstrate that different transgenes can be inserted therein rapidly and efficiently through recombinase-mediated cassette exchange (RMCE). The LiPS-A3 line can greatly facilitate the insertion of reporter and other genes in hPSCs. Targeting transgenes in the LiPS-A3S genomic locus can find broad applications in stem cell research and possibly cell and gene therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898090", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 1036, "text": "We selected one clone, LiPS-A3 with an integration site in chromosome 15 maintaining robust expression without silencing and demonstrate that different transgenes can be inserted therein rapidly and efficiently through recombinase-mediated cassette exchange (RMCE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898090", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 1044, "text": "We selected one clone , LiPS-A3 with an integration site in chromosome 15 maintaining robust expression without silencing and demonstrate that different transgenes can be inserted therein rapidly and efficiently through recombinase-mediated cassette exchange ( RMCE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898090", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 1037, "text": "We selected one clone, LiPS-A3 with an integration site in chromosome 15 maintaining robust expression without silencing and demonstrate that different transgenes can be inserted therein rapidly and efficiently through recombinase-mediated cassette exchange (RMCE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27898090", "endSection": "abstract" } ] }, { "body": "What is a J pouch?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29577558", "http://www.ncbi.nlm.nih.gov/pubmed/29125801", "http://www.ncbi.nlm.nih.gov/pubmed/29453211", "http://www.ncbi.nlm.nih.gov/pubmed/29787362" ], "ideal_answer": [ "The j pouch is a colonic j-pouch with anastomosis to the rectal stump. It is an accepted form of reconstruction after low anterior resection (lar) for rectal carcinoma.", "Formation of a colonic J-pouch with anastomosis to the rectal stump is an accepted form of reconstruction after low anterior resection (LAR) for rectal carcinoma total proctocolectomy with outcomes after ileal J-pouch anal anastomosis (IPAA) at a single institution", "After a proctocolectomy or surgery for ulcerative colitis or rectal carcinoma, a ileal J-pouch anal anastomosis (IPAA) or J pouch. Formation of a colonic J-pouch with anastomosis to the rectal stump is an accepted form of reconstruction after low anterior resection (LAR)." ], "type": "summary", "id": "5e3daf7648dab47f26000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Formation of a colonic J-pouch with anastomosis to the rectal stump is an accepted form of reconstruction after low anterior resection (LAR) for rectal carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29453211", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 189, "text": "total proctocolectomy with outcomes after ileal J-pouch anal anastomosis (IPAA) at a single institution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125801", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 410, "text": "A random effects meta-analytical model was used to compare adverse events and functional outcome.RESULTS: Thirty comparative studies comparing J, W, S and K pouch designs were included", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29577558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Ileal pouch-anal anastomosis, or J pouch, surgery has become the procedure of choice for treatment of medically refractory ulcerative colitis and familial adenomatous polyposis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29787362", "endSection": "abstract" } ] }, { "body": "What is the function of the protein encoded by the gene NKCC2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29357410", "http://www.ncbi.nlm.nih.gov/pubmed/29407172", "http://www.ncbi.nlm.nih.gov/pubmed/29412704", "http://www.ncbi.nlm.nih.gov/pubmed/30113482" ], "ideal_answer": [ "The protein function as an Na-K-Cl cotransporter." ], "exact_answer": [ "This protein functions as an Na-K-Cl cotransporter." ], "type": "factoid", "id": "5e80489b835f4e4777000022", "snippets": [ { "offsetInBeginSection": 1002, "offsetInEndSection": 1040, "text": "2 chloride co-transporter (NKCC2) gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29407172", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 732, "text": "Na-K-2Cl cotransporter (NKCC2) function ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29412704", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 700, "text": "Na-K-Cl cotransporter 2 (NKCC2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29357410", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 288, "text": "SLC12A1 (NKCC2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30113482", "endSection": "abstract" } ] }, { "body": "Is celecoxib effective for amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18608093", "http://www.ncbi.nlm.nih.gov/pubmed/16802291" ], "ideal_answer": [ "No. In a clinical trial, celecoxib did not have a beneficial effect on patients with amyotrophic lateral sclerosis." ], "exact_answer": "no", "type": "yesno", "id": "5e4b5f566d0a277941000020", "snippets": [ { "offsetInBeginSection": 1507, "offsetInEndSection": 1648, "text": "In conclusion, the celecoxib-creatine combination was selected as preferable to the minocycline-creatine combination for further evaluation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18608093", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 983, "text": "ESULTS: Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1326, "text": "INTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1331, "text": "INTERPRETATION\n\nAt the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 986, "text": "RESULTS\n\nCelecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 986, "text": "RESULTS\nCelecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1325, "text": "INTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 982, "text": "RESULTS: Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1283, "text": "At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 955, "text": "Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16802291", "endSection": "abstract" } ] }, { "body": "Is the protein MCL-1 anti-apoptotic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28949029", "http://www.ncbi.nlm.nih.gov/pubmed/28905990", "http://www.ncbi.nlm.nih.gov/pubmed/28960207" ], "ideal_answer": [ "Yes, MCL-1 is an anti-apoptotic protein." ], "exact_answer": "yes", "type": "yesno", "id": "5e6e8600c6a8763d23000002", "snippets": [ { "offsetInBeginSection": 1002, "offsetInEndSection": 1075, "text": "increased expression of anti-apoptotic proteins (Bcl-xL, Mcl-1 and XIAP) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28949029", "endSection": "abstract" }, { "offsetInBeginSection": 1187, "offsetInEndSection": 1249, "text": "repression of anti-apoptotic proteins (Mcl-1, Bcl-xl and XIAP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905990", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 695, "text": "anti-apoptotic BCL-2 family members, such as BCL-2, BCL-XL or MCL-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28960207", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of Trilaciclib.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31504118", "http://www.ncbi.nlm.nih.gov/pubmed/29726787", "http://www.ncbi.nlm.nih.gov/pubmed/28446688" ], "ideal_answer": [ "Trilaciclib is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, which act by inhibiting progression from the G1 to S phases of the cell cycle." ], "type": "summary", "id": "5e4b56276d0a27794100001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29726787", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 671, "text": "We show that the coadministration of G1T28 (trilaciclib), which is a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil treatment model. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28446688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29726787", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 670, "text": "We show that the coadministration of G1T28 (trilaciclib), which is a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil treatment model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28446688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29726787", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 684, "text": "We show that the coadministration of G1T28 ( trilaciclib) , which is a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 ( CDK4/6) , contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells ( HSCs ) from chemotherapy-induced exhaustion in a serial 5-fluorouracil treatment model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28446688", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 277, "text": "Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy ( myelopreservation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31504118", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 287, "text": "Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31504118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31504118", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29726787", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 275, "text": "Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31504118", "endSection": "abstract" } ] }, { "body": "How is ZP-PTH delivered to patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20567999" ], "ideal_answer": [ "ZP-PTH uses a transdermal drug-coated microneedle patch system." ], "exact_answer": [ "transdermal drug-coated microneedle patch system" ], "type": "factoid", "id": "5e7f64d6835f4e477700001f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 169, "text": "To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20567999", "endSection": "abstract" } ] }, { "body": "Which disease is ZP-PTH used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20567999" ], "ideal_answer": [ "ZP-PTH is used for the treatment of osteoporosis." ], "exact_answer": [ "Osteoporosis" ], "type": "factoid", "id": "5e7f6971835f4e4777000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Parathyroid hormone (1-34)-coated microneedle patch system: clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20567999", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 169, "text": "To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20567999", "endSection": "abstract" } ] }, { "body": "Which gene is mutated in the classic Bartter's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15056980", "http://www.ncbi.nlm.nih.gov/pubmed/28555925", "http://www.ncbi.nlm.nih.gov/pubmed/19050915", "http://www.ncbi.nlm.nih.gov/pubmed/9587066" ], "ideal_answer": [ "Classic Bartter's syndrome has been demonstrated to result from defective chloride transport across the basolateral membrane in the distal nephron due to mutations in the chloride channel gene CLCNKB." ], "exact_answer": [ "Classic Bartter's syndrome has been demonstrated to result from defective chloride transport across the basolateral membrane in the distal nephron due to mutations in the chloride channel gene CLCNKB." ], "type": "factoid", "id": "5e805e62835f4e4777000023", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 308, "text": "The highly variable phenotypes observed in patients with classic Bartter's syndrome (BS) remain unsatisfactorily explained. The wide spectrum of functional severity of CLCNKB mutations may contribute to the phenotypic variability, and the genotype-phenotype association has not been established. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28555925", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 156, "text": "Progressive renal failure in patients with classic Bartter's syndrome (cBS) due to inactivating mutations in CLCNKB gene is extraordinarily rare", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19050915", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 462, "text": "classic Bartter's syndrome by mutations of ClC-Kb", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15056980", "endSection": "abstract" }, { "offsetInBeginSection": 1393, "offsetInEndSection": 1593, "text": "Classic Bartter's syndrome has been demonstrated to result from defective chloride transport across the basolateral membrane in the distal nephron due to mutations in the chloride channel gene CLCNKB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9587066", "endSection": "abstract" } ] }, { "body": "What is the purpose of the Unique Connectivity of Uncharged Compounds (UC2) search tool?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29040459" ], "ideal_answer": [ "The Unique Connectivity of Uncharged Compounds (UC2) search tool uses unique connectivity of uncharged compounds for metabolite annotation by database searching in mass spectrometry-based metabolomics.", "The Unique Connectivity of Uncharged Compounds (UC2) search tool uses unique connectivity of uncharged compounds for metabolite annotation by database searching in mass spectrometry-based metabolomics. The UC2 search tool is available at http://unc.bioqrator.org/UC2/.", "The Unique Connectivity of Uncharged Compounds (UC2) search tool is used for metabolite annotation by database searching in mass spectrometry-based metabolomics.", "For metabolite annotation in metabolomics, variations in the registered states of compounds (charged molecules and multiple components, such as salts) and their redundancy among compound databases could be the cause of misannotations and hamper immediate recognition of the uniqueness of metabolites while searching by mass values measured using mass spectrometry. The search system named UC2 (Unique Connectivity of Uncharged Compounds) has been developed where compounds are tentatively neutralized into uncharged states and stored on the basis of their unique connectivity of atoms after removing their stereochemical information using the first block in the hash of the IUPAC International Chemical Identifier, by which false-positive hits are remarkably reduced, both charged and uncharged compounds are properly searched in a single query and records having a unique connectivity are compiled in a single search result." ], "exact_answer": [ "Metabolite annotation by database searching in mass spectrometry-based metabolomics" ], "type": "factoid", "id": "5e52a3416d0a277941000043", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "UC2 search: using unique connectivity of uncharged compounds for metabolite annotation by database searching in mass spectrometry-based metabolomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040459", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1095, "text": "For metabolite annotation in metabolomics, variations in the registered states of compounds (charged molecules and multiple components, such as salts) and their redundancy among compound databases could be the cause of misannotations and hamper immediate recognition of the uniqueness of metabolites while searching by mass values measured using mass spectrometry. We developed a search system named UC2 (Unique Connectivity of Uncharged Compounds), where compounds are tentatively neutralized into uncharged states and stored on the basis of their unique connectivity of atoms after removing their stereochemical information using the first block in the hash of the IUPAC International Chemical Identifier, by which false-positive hits are remarkably reduced, both charged and uncharged compounds are properly searched in a single query and records having a unique connectivity are compiled in a single search result.Availability and implementation: The UC2 search tool is available free of charge as a REST web service (http://webs2.kazusa.or.jp/mfsearcher) and a Java-based GUI tool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "UC2 search: using unique connectivity of uncharged compounds for metabolite annotation by database searching in mass spectrometry-based metabolomics", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040459", "endSection": "title" }, { "offsetInBeginSection": 374, "offsetInEndSection": 1210, "text": "We developed a search system named UC2 (Unique Connectivity of Uncharged Compounds), where compounds are tentatively neutralized into uncharged states and stored on the basis of their unique connectivity of atoms after removing their stereochemical information using the first block in the hash of the IUPAC International Chemical Identifier, by which false-positive hits are remarkably reduced, both charged and uncharged compounds are properly searched in a single query and records having a unique connectivity are compiled in a single search result.Availability and implementation: The UC2 search tool is available free of charge as a REST web service (http://webs2.kazusa.or.jp/mfsearcher) and a Java-based GUI tool.Contact: sakurai@kazusa.or.jp.Supplementary information: Supplementary data are available at Bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29040459", "endSection": "abstract" } ] }, { "body": "Name a selective NK3R agonist.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29902942" ], "ideal_answer": [ "Senktide is a highly potent and selective NK3R agonist." ], "exact_answer": [ "senktide" ], "type": "factoid", "id": "5e5438c3b761aafe09000003", "snippets": [ { "offsetInBeginSection": 948, "offsetInEndSection": 1153, "text": "Administration of senktide, highly potent and selective NK3R agonist, resulted in increase of serum LH concentration, induction of VMS, increase in heart rate, and skin temperature in postmenopausal women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29902942", "endSection": "abstract" } ] }, { "body": "What is the target of the drug Olmesartan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29872491", "http://www.ncbi.nlm.nih.gov/pubmed/29414040", "http://www.ncbi.nlm.nih.gov/pubmed/30217371" ], "ideal_answer": [ "Olmesartan (OL) is the pharmacologically active metabolite of Olmesartan medoxomil (OM), an FDA-approved angiotensin II receptor antagonist for administrating cardiovascular diseases" ], "exact_answer": [ "angiotensin II receptor" ], "type": "factoid", "id": "5e808ef4835f4e477700002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Olmesartan (OL) is the pharmacologically active metabolite of Olmesartan medoxomil (OM), an FDA-approved angiotensin II receptor antagonist for administrating cardiovascular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29414040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "Either angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor 1 blocker (ARB) attenuates cardiac remodeling. However, the overall molecular modulation of the reversing remodeling process in response to the ACEI or ARB treatment is not yet well determined. In this study, we examined whether gene expressions are modulated by ACEI (temocapril), ARB (olmesartan)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29872491", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 262, "text": " ARB olmesartan (OLM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30217371", "endSection": "abstract" } ] }, { "body": "In which cells does TLR7 escape X-chromosome inactivation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16887967", "http://www.ncbi.nlm.nih.gov/pubmed/29374079", "http://www.ncbi.nlm.nih.gov/pubmed/30276444" ], "ideal_answer": [ "The tlr7 gene encodes by an x chromosome locus. Tlr7 is encoded by an x-chromosome inactivation in immune cells from women and klinefelter syndrome patients.", "TLR7 evades silencing by X chromosome inactivation in immune cells.", "TLR7 escape X-chromosome inactivation by RNA polymerase II (ChIP-seq) DNA methylation to produce active TLR7 in immune cells", "TLR7 escape X-chromosome inactivation by becoming activated in response to DNA damage caused by biallelic loss-of-function mutations on the X chromosome. In addition, TLR7 expression can also be observed in a dose-dependent manner in immune cells, such as epithelial cells, monocytes and macrophages.", "immune cells", "TLR7 is encoded by an X chromosome locus, and we examined here whether the TLR7 gene evades silencing by X chromosome inactivation in immune cells from women and Klinefelter syndrome males" ], "exact_answer": [ "immune cells" ], "type": "factoid", "id": "5d38767ca1e159510500000b", "snippets": [ { "offsetInBeginSection": 417, "offsetInEndSection": 606, "text": " TLR7 is encoded by an X chromosome locus, and we examined here whether the TLR7 gene evades silencing by X chromosome inactivation in immune cells from women and Klinefelter syndrome males", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374079", "endSection": "abstract" }, { "offsetInBeginSection": 995, "offsetInEndSection": 1209, "text": "X-inactivation escape of the TLR7 gene was investigated in monoclonal B cell lines and, independently, in pDCs after cell sorting and single-cell picking, indicating regular silencing of one TLR7 allele in females.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16887967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30276444", "endSection": "title" } ] }, { "body": "Which tool has been developed for prediction of single-cell DNA methylation states using deep learning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28395661" ], "ideal_answer": [ "DeepCpG is a computational approach based on deep neural networks to predict methylation states in single cells. By evaluating DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols it turns out that DeepCpG yields substantially more accurate predictions than previous methods.", "DeepCpG is a computational approach based on deep neural networks to predict single-cell DNA methylation states in single cells." ], "exact_answer": [ "DeepCpG" ], "type": "factoid", "id": "5e52a7b66d0a277941000045", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395661", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 746, "text": "Recent technological advances have enabled DNA methylation to be assayed at single-cell resolution. However, current protocols are limited by incomplete CpG coverage and hence methods to predict missing methylation states are critical to enable genome-wide analyses. We report DeepCpG, a computational approach based on deep neural networks to predict methylation states in single cells. We evaluate DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols. DeepCpG yields substantially more accurate predictions than previous methods. Additionally, we show that the model parameters can be interpreted, thereby providing insights into how sequence composition affects methylation variability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395661", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 387, "text": "We report DeepCpG, a computational approach based on deep neural networks to predict methylation states in single cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395661", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 510, "text": "We evaluate DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395661", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 388, "text": "We report DeepCpG, a computational approach based on deep neural networks to predict methylation states in single cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395661", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 511, "text": "We evaluate DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28395661", "endSection": "abstract" } ] }, { "body": "When was vaxchora first licensed by the FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27425792" ], "ideal_answer": [ "Vaxchora was licensed by the FDA on June 10 2016." ], "exact_answer": [ "10 June 2016" ], "type": "factoid", "id": "5e7644a2c6a8763d23000014", "snippets": [ { "offsetInBeginSection": 965, "offsetInEndSection": 1108, "text": "After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27425792", "endSection": "abstract" } ] }, { "body": "What is the active ingredient of Eligard?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29197875" ], "ideal_answer": [ "The active ingredient of Eligard is leuprorelin acetate." ], "exact_answer": [ "Leuprorelin acetate" ], "type": "factoid", "id": "5e7745ea835f4e4777000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Efficacy and Tolerability of Leuprorelin Acetate (Eligard\u00ae) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29197875", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 242, "text": "We evaluated the efficacy and tolerability of 3- and 6-month leuprorelin acetate (LA) depot formulations (Eligard\u00ae, Astellas Pharma GmbH) in patients with advanced prostate cancer treated in routine clinical practice in Germany.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29197875", "endSection": "abstract" } ] }, { "body": "Which company produces Eligard?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29197875" ], "ideal_answer": [ "Eligard is produced by Astellas Pharma GmbH." ], "exact_answer": [ "Astellas Pharma GmbH" ], "type": "factoid", "id": "5e776443835f4e4777000008", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 242, "text": "We evaluated the efficacy and tolerability of 3- and 6-month leuprorelin acetate (LA) depot formulations (Eligard\u00ae, Astellas Pharma GmbH) in patients with advanced prostate cancer treated in routine clinical practice in Germany.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29197875", "endSection": "abstract" } ] }, { "body": "Which type of distance is used in the R-package XenofilteR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30286710" ], "ideal_answer": [ "The R-package XenofilteR separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome.", "XenofilteR separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome." ], "exact_answer": [ "Edit-distance" ], "type": "factoid", "id": "5e52be146d0a27794100004a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "XenofilteR: computational deconvolution of mouse and human reads in tumor xenograft sequence data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286710", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1391, "text": "Mouse xenografts from (patient-derived) tumors (PDX) or tumor cell lines are widely used as models to study various biological and preclinical aspects of cancer. However, analyses of their RNA and DNA profiles are challenging, because they comprise reads not only from the grafted human cancer but also from the murine host. The reads of murine origin result in false positives in mutation analysis of DNA samples and obscure gene expression levels when sequencing RNA. However, currently available algorithms are limited and improvements in accuracy and ease of use are necessary.RESULTS: We developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome. To assess the accuracy of XenofilteR, we generated sequence data by in silico mixing of mouse and human DNA sequence data. These analyses revealed that XenofilteR removes >\u200999.9% of sequence reads of mouse origin while retaining human sequences. This allowed for mutation analysis of xenograft samples with accurate variant allele frequencies, and retrieved all non-synonymous somatic tumor mutations.CONCLUSIONS: XenofilteR accurately dissects RNA and DNA sequences from mouse and human origin, thereby outperforming currently available tools. XenofilteR is open source and available at https://github.com/PeeperLab/XenofilteR .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286710", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 763, "text": "RESULTS\n\nWe developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286710", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 760, "text": "RESULTS We developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286710", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 763, "text": "RESULTS\nWe developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286710", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 761, "text": "RESULTS: We developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286710", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 741, "text": "We developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286710", "endSection": "abstract" } ] }, { "body": "How many copies of TP53 does the elephant genome contain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27642012", "http://www.ncbi.nlm.nih.gov/pubmed/26447779" ], "ideal_answer": [ " Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction.", " Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction.", "Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction.", "20", "Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the emergence of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway.", "While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction.", "In the elephant genome, TP53 is encoded by 20 copies.", "Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage.", "The elephant genome encodes 20 copies of the tumor suppressor gene tp53 and that the evolution of large body sizes, the evolves of extreme sensitivity to genotoxic stress, and a hyperactive tp53 signaling pathway in the elephant (proboscidean) lineage have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction." ], "exact_answer": [ "20" ], "type": "factoid", "id": "5d388535a1e1595105000018", "snippets": [ { "offsetInBeginSection": 246, "offsetInEndSection": 578, "text": "Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27642012", "endSection": "abstract" }, { "offsetInBeginSection": 1761, "offsetInEndSection": 2003, "text": "While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26447779", "endSection": "abstract" } ] }, { "body": "Which company originally developed the drug Afrezza?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20462282" ], "ideal_answer": [ "The inhaled insulin Technosphere, also known as Afrezza is produced by the MannKind Corporation." ], "exact_answer": [ "MannKind Corporation" ], "type": "factoid", "id": "5e776a75835f4e477700000d", "snippets": [ { "offsetInBeginSection": 605, "offsetInEndSection": 882, "text": "MannKind Corporation has developed a powder formulation of insulin that allows for a high percentage of the administered insulin to be absorbed via the lung. Their product, AFREZZA (Technosphere insulin), is currently under review by the FDA for use in patients with diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20462282", "endSection": "abstract" } ] }, { "body": "Which tool exist for predicting drug synergy with deep learning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29253077" ], "ideal_answer": [ "Deep Learning has had an impact in many research areas by achieving new state-of-the-art model performance. DeepSynergy has been developed as a tool that uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies.", "DeepSynergy is an online tool for predicting drug synergy with deep learning. It is a method for predicting anti-cancer drug synergy based on a semi-supervised learning algorithm that is trained on a corpus of k-nearest neighbor data and combines pharmacological, structural and pharmacological features extracted from a large variety of biological datasets." ], "exact_answer": [ "DeepSynergy" ], "type": "factoid", "id": "5e2b00bc76af173751000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "DeepSynergy: predicting anti-cancer drug synergy with Deep Learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "title" }, { "offsetInBeginSection": 380, "offsetInEndSection": 1851, "text": "Recently, Deep Learning has had an impact in many research areas by achieving new state-of-the-art model performance. However, Deep Learning has not yet been applied to drug synergy prediction, which is the approach we present here, termed DeepSynergy. DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies.Results: DeepSynergy was compared to other machine learning methods such as Gradient Boosting Machines, Random Forests, Support Vector Machines and Elastic Nets on the largest publicly available synergy dataset with respect to mean squared error. DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines. At this task, the mean Pearson correlation coefficient between the measured and the predicted values of DeepSynergy was 0.73. Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90. Furthermore, we found that all compared methods exhibit low predictive performance when extrapolating to unexplored drugs or cell lines, which we suggest is due to limitations in the size and diversity of the dataset. We envision that DeepSynergy could be a valuable tool for selecting novel synergistic drug combinations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1062, "text": "Results\n\nDeepSynergy was compared to other machine learning methods such as Gradient Boosting Machines, Random Forests, Support Vector Machines and Elastic Nets on the largest publicly available synergy dataset with respect to mean squared error.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1750, "offsetInEndSection": 1854, "text": "We envision that DeepSynergy could be a valuable tool for selecting novel synergistic drug combinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1531, "text": "Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 814, "text": "DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1271, "text": "DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 632, "text": "However, Deep Learning has not yet been applied to drug synergy prediction, which is the approach we present here, termed DeepSynergy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1062, "text": "Results\nDeepSynergy was compared to other machine learning methods such as Gradient Boosting Machines, Random Forests, Support Vector Machines and Elastic Nets on the largest publicly available synergy dataset with respect to mean squared error.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 814, "text": "DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1271, "text": "DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1749, "offsetInEndSection": 1854, "text": "We envision that DeepSynergy could be a valuable tool for selecting novel synergistic drug combinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1397, "offsetInEndSection": 1531, "text": "Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 1060, "text": "DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies.Results: DeepSynergy was compared to other machine learning methods such as Gradient Boosting Machines, Random Forests, Support Vector Machines and Elastic Nets on the largest publicly available synergy dataset with respect to mean squared error.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1269, "text": "DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1396, "offsetInEndSection": 1529, "text": "Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 486, "offsetInEndSection": 620, "text": "However, Deep Learning has not yet been applied to drug synergy prediction, which is the approach we present here, termed DeepSynergy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1728, "offsetInEndSection": 1832, "text": "We envision that DeepSynergy could be a valuable tool for selecting novel synergistic drug combinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1509, "text": "Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 802, "text": "DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1249, "text": "DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29253077", "endSection": "abstract" } ] }, { "body": "Is ozanezumab effective for amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28139349" ], "ideal_answer": [ "No. Ozanezumab did not show efficacy compared with placebo in patients with amyotrophic lateral sclerosis. Therefore, Nogo-A does not seem to be an effective therapeutic target in ALS." ], "exact_answer": "no", "type": "yesno", "id": "5e48bd2ed14c9f295d000017", "snippets": [ { "offsetInBeginSection": 1424, "offsetInEndSection": 1627, "text": "The adjusted mean of the joint-rank score was -14\u00b79 (SE 13\u00b75) for the ozanezumab group and 15\u00b70 (13\u00b76) for the placebo group, with a least squares mean difference of -30\u00b70 (95% CI -67\u00b79 to 7\u00b79; p=0\u00b712). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139349", "endSection": "abstract" }, { "offsetInBeginSection": 2422, "offsetInEndSection": 2592, "text": "INTERPRETATION: Ozanezumab did not show efficacy compared with placebo in patients with ALS. Therefore, Nogo-A does not seem to be an effective therapeutic target in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139349", "endSection": "abstract" }, { "offsetInBeginSection": 2450, "offsetInEndSection": 2542, "text": "INTERPRETATION\n\nOzanezumab did not show efficacy compared with placebo in patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139349", "endSection": "abstract" }, { "offsetInBeginSection": 1450, "offsetInEndSection": 1652, "text": "The adjusted mean of the joint-rank score was -14\u00b79 (SE 13\u00b75) for the ozanezumab group and 15\u00b70 (13\u00b76) for the placebo group, with a least squares mean difference of -30\u00b70 (95% CI -67\u00b79 to 7\u00b79; p=0\u00b712).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139349", "endSection": "abstract" }, { "offsetInBeginSection": 2423, "offsetInEndSection": 2514, "text": "INTERPRETATION Ozanezumab did not show efficacy compared with placebo in patients with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139349", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1415, "text": "The adjusted mean of the joint-rank score was -14\u00b79 (SE 13\u00b75) for the ozanezumab group and 15\u00b70 (13\u00b76) for the placebo group, with a least squares mean difference of -30\u00b70 (95% CI -67\u00b79 to 7\u00b79; p=0\u00b712).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28139349", "endSection": "abstract" } ] }, { "body": "Is Dexmecamylamine effective for depression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24408516", "http://www.ncbi.nlm.nih.gov/pubmed/24507016", "http://www.ncbi.nlm.nih.gov/pubmed/25514064" ], "ideal_answer": [ "No. Antidepressant effect of Dexmecamylamine (TC-5214) was not observed in clinical trials." ], "exact_answer": "no", "type": "yesno", "id": "5e4b62946d0a277941000024", "snippets": [ { "offsetInBeginSection": 1075, "offsetInEndSection": 1277, "text": "At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo. Furthermore, there were no significant differences in any of the secondary endpoints. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24507016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24408516", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1700, "text": "In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1-4 mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated. In conclusion, no antidepressant effect of TC-5214 was observed in these studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24507016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24408516", "endSection": "abstract" }, { "offsetInBeginSection": 1718, "offsetInEndSection": 1819, "text": "No notable differences were observed between dexmecamylamine and placebo for any secondary end point.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25514064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "TC-5214 ( dexmecamylamine ) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder ( MDD ) and is currently being evaluated by Targacept as a treatment for overactive bladder . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24408516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24408516", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1191, "text": "At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24507016", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1619, "text": "In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1-4 mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24507016", "endSection": "abstract" } ] }, { "body": "Which cloud-based platform has been developed for comparing GWAS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27986896" ], "ideal_answer": [ "EasyGWAS is a cloud-based platform for comparing the results of Genome-Wide Association Studies (GWAS).", "The ever- growing availability of high-quality genotypes for a multitude of species has enabled researchers to explore the underlying genetic architecture of complex phenotypes at an unprecedented level of detail using genome-wide association studies (GWAS). The systematic comparison of results obtained from GWAS of different traits opens up new possibilities, including the analysis of pleiotropic effects. In order to facilitate the simple comparison of GWAS results, easyGWAS has been developed as a powerful, species-independent online resource for computing, storing, sharing, annotating, and comparing GWAS." ], "exact_answer": [ "easyGWAS" ], "type": "factoid", "id": "5e52add36d0a277941000047", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "easyGWAS: A Cloud-Based Platform for Comparing the Results of Genome-Wide Association Studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1361, "text": "The ever-growing availability of high-quality genotypes for a multitude of species has enabled researchers to explore the underlying genetic architecture of complex phenotypes at an unprecedented level of detail using genome-wide association studies (GWAS). The systematic comparison of results obtained from GWAS of different traits opens up new possibilities, including the analysis of pleiotropic effects. Other advantages that result from the integration of multiple GWAS are the ability to replicate GWAS signals and to increase statistical power to detect such signals through meta-analyses. In order to facilitate the simple comparison of GWAS results, we present easyGWAS, a powerful, species-independent online resource for computing, storing, sharing, annotating, and comparing GWAS. The easyGWAS tool supports multiple species, the uploading of private genotype data and summary statistics of existing GWAS, as well as advanced methods for comparing GWAS results across different experiments and data sets in an interactive and user-friendly interface. easyGWAS is also a public data repository for GWAS data and summary statistics and already includes published data and results from several major GWAS. We demonstrate the potential of easyGWAS with a case study of the model organism Arabidopsis thaliana, using flowering and growth-related traits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 793, "text": "In order to facilitate the simple comparison of GWAS results, we present easyGWAS, a powerful, species-independent online resource for computing, storing, sharing, annotating, and comparing GWAS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1063, "text": "The easyGWAS tool supports multiple species, the uploading of private genotype data and summary statistics of existing GWAS, as well as advanced methods for comparing GWAS results across different experiments and data sets in an interactive and user-friendly interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1215, "text": "easyGWAS is also a public data repository for GWAS data and summary statistics and already includes published data and results from several major GWAS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "easyGWAS: A Cloud-Based Platform for Comparing the Results of Genome-Wide Association Studies", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "title" }, { "offsetInBeginSection": 806, "offsetInEndSection": 1076, "text": "The easyGWAS tool supports multiple species , the uploading of private genotype data and summary statistics of existing GWAS , as well as advanced methods for comparing GWAS results across different experiments and data sets in an interactive and user-friendly interface", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 804, "text": "In order to facilitate the simple comparison of GWAS results , we present easyGWAS , a powerful , species-independent online resource for computing , storing , sharing , annotating , and comparing GWAS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1228, "text": "easyGWAS is also a public data repository for GWAS data and summary statistics and already includes published data and results from several major GWAS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1064, "text": "The easyGWAS tool supports multiple species, the uploading of private genotype data and summary statistics of existing GWAS, as well as advanced methods for comparing GWAS results across different experiments and data sets in an interactive and user-friendly interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 794, "text": "In order to facilitate the simple comparison of GWAS results, we present easyGWAS, a powerful, species-independent online resource for computing, storing, sharing, annotating, and comparing GWAS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1216, "text": "easyGWAS is also a public data repository for GWAS data and summary statistics and already includes published data and results from several major GWAS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1361, "text": "We demonstrate the potential of easyGWAS with a case study of the model organism Arabidopsis thaliana, using flowering and growth-related traits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27986896", "endSection": "abstract" } ] }, { "body": "Can CMB305 be used against sarcomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29280411" ], "ideal_answer": [ "Yes, the CMB205 vaccine is aimed at synovial sarcoma and myxoid/round cell liposarcoma patients." ], "exact_answer": "yes", "type": "yesno", "id": "5e7f64a5835f4e477700001e", "snippets": [ { "offsetInBeginSection": 814, "offsetInEndSection": 985, "text": "CMB305 induces NY-ESO-1 specific T cell responses in both SS and MRC patients and these patients had excellent overall survival (OS) outcomes in the initial phase I study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29280411", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1341, "text": "Data suggesting this vaccine may improve OS for SS and MRCL patients is exciting but early, and on-going work is testing the impact of CMB305 on patient outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29280411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29280411", "endSection": "title" } ] }, { "body": "What is Quadracel?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27069343" ], "ideal_answer": [ "Quadracel (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, Sanofi Pasteur Inc.) is a new vaccination developed to condense the last dose of both DTaP and IPV so they do not have to be given separately, thus reducing the total number of vaccinations required. In a randomized, controlled, phase 3, pivotal trial, Quadracel proved to be as efficacious and safe as Daptacel (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed, Sanofi Pasteur Inc.) and IPOL (poliovirus vaccine inactivated, Sanofi Pasteur Inc.), given separately, to children between the ages of 4 and 6 years." ], "type": "summary", "id": "5e7f61ed835f4e477700001c", "snippets": [ { "offsetInBeginSection": 620, "offsetInEndSection": 930, "text": "Quadracel (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, Sanofi Pasteur Inc.) is a new vaccination developed to condense the last dose of both DTaP and IPV so they do not have to be given separately, thus reducing the total number of vaccinations required.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27069343", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1375, "text": " In a randomized, controlled, phase 3, pivotal trial, Quadracel proved to be as efficacious and safe as Daptacel (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed, Sanofi Pasteur Inc.) and IPOL (poliovirus vaccine inactivated, Sanofi Pasteur Inc.), given separately, to children between the ages of 4 and 6 years", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27069343", "endSection": "abstract" } ] }, { "body": "What delivery system is used for the Fluzone Intradermal vaccine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22149703" ], "ideal_answer": [ "Fluzone was the first influenza vaccine licensed in the USA that uses a new microinjection system for intradermal delivery of vaccines (Soluvia(tm), Becton Dickinson)." ], "exact_answer": [ "Microinjection system for intradermal vaccine delivery" ], "type": "factoid", "id": "5e7f5d83835f4e4777000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "On May 9 2011, the US FDA approved Sanofi Pasteur's Fluzone(\u00ae) Intradermal influenza vaccine, the first influenza vaccine licensed in the USA that uses a new microinjection system for intradermal delivery of vaccines (Soluvia\u2122, Becton Dickinson). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22149703", "endSection": "abstract" } ] }, { "body": "Name two inhalable insulin products.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25485886" ], "ideal_answer": [ "Despite discontinuation of the first inhalable insulin, Exubera(r), due to suboptimal market acceptance, development of orally inhaled insulin delivery systems has been galvanized by the recent approval of Afrezza(r)." ], "exact_answer": [ [ "Exubera" ], [ "Afrezza" ] ], "type": "list", "id": "5e7768f9835f4e477700000b", "snippets": [ { "offsetInBeginSection": 196, "offsetInEndSection": 446, "text": "Despite discontinuation of the first inhalable insulin, Exubera\u00ae, due to suboptimal market acceptance, development of orally inhaled insulin delivery systems has been galvanized by the recent approval of Afrezza\u00ae and several others awaiting approval.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25485886", "endSection": "abstract" } ] }, { "body": "How is the mouse Fxy gene evolving?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12615004", "http://www.ncbi.nlm.nih.gov/pubmed/9425238", "http://www.ncbi.nlm.nih.gov/pubmed/17418442", "http://www.ncbi.nlm.nih.gov/pubmed/10508587" ], "ideal_answer": [ " Here, we report that the rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique.", "The rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique." ], "type": "summary", "id": "5d387e74a1e1595105000012", "snippets": [ { "offsetInBeginSection": 231, "offsetInEndSection": 572, "text": "We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. Therefore, this gene might be in a state of transition between pseudoautosomal and X-unique locations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9425238", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1323, "text": " Here, we report that the rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10508587", "endSection": "abstract" }, { "offsetInBeginSection": 1324, "offsetInEndSection": 1403, "text": "Thus, chromosomal position can directly affect the rate of evolution of a gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10508587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The mouse Fxy gene was translocated into the highly recombining pseudoautosomal region comparatively recently in evolutionary terms. This event resulted in a rapid increase of GC content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615004", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 703, "text": "These results strongly suggest that recombination is the primary determinant of the isochore organization of mammalian genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615004", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 569, "text": "Such an accelerated rate of evolution might be due to factors other than natural selection, in particular GC-biased gene conversion. This is true of neutral sequences, but also of constrained sequences, which can be illustrated using the mouse Fxy gen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17418442", "endSection": "abstract" } ] }, { "body": "How long in bp is the human pseudoautosomal region 2 (PAR2)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25375121", "http://www.ncbi.nlm.nih.gov/pubmed/2847916", "http://www.ncbi.nlm.nih.gov/pubmed/2885758", "http://www.ncbi.nlm.nih.gov/pubmed/18660847", "http://www.ncbi.nlm.nih.gov/pubmed/12566406" ], "ideal_answer": [ "The human pseudoautosomal region 2 (PAR2), which is located in the long arm of chromosome 9 (LTR6B) and consists of 32 exons, is320-kb long.", "The 320-kb human pseudoautosomal region 2 (PAR2) at the tips of the long arms of the X and Y chromosomes is thought to have been duplicated onto the Y chromosome recently in primate evolution", "The human pseudoautosomal region 2 (PAR2) is 320-kb long." ], "exact_answer": [ "320kbp" ], "type": "factoid", "id": "5d387f24a1e1595105000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "The human sex chromosomes differ in sequence, except for the pseudoautosomal regions (PAR) at the terminus of the short and the long arms, denoted as PAR1 and PAR2. The boundary between PAR1 and the unique X and Y sequences was established during the divergence of the great apes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25375121", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 776, "text": "The insertion is generated by non-allelic homologous recombination between a 548 bp LTR6B repeat within the Y chromosome PAR1 and a second LTR6B repeat located 105 kb from the PAR boundary on the X chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25375121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "The pseudoautosomal regions (PAR1 and PAR2) of the human X and Y chromosomes pair and recombine during meiosis. Thus genes in this region are not inherited in a strictly sex-linked fashion. PAR1 is located at the terminal region of the short arms and PAR2 at the tips of the long arms of these chromosomes. To date, 24 genes have been assigned to the PAR1 region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18660847", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 474, "text": "In contrast, so far only 4 genes have been discovered in the PAR2 region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18660847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The 320-kb human pseudoautosomal region 2 (PAR2) at the tips of the long arms of the X and Y chromosomes is thought to have been duplicated onto the Y chromosome recently in primate evolution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12566406", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 361, "text": " The four genes within PAR2 have been proposed to constitute two zones with different base ratios and transcription, one of which was added recently to the X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12566406", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 356, "text": " This map extends 2.3 Mbp from the telomere to sex-chromosome-specific DNA, includes at least seven CpG islands and locates four genetically mapped loci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2847916", "endSection": "abstract" } ] }, { "body": "Does teplizumab hold promise for diabetes prevention?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23086558", "http://www.ncbi.nlm.nih.gov/pubmed/30569273", "http://www.ncbi.nlm.nih.gov/pubmed/25941654", "http://www.ncbi.nlm.nih.gov/pubmed/31533907", "http://www.ncbi.nlm.nih.gov/pubmed/22968521", "http://www.ncbi.nlm.nih.gov/pubmed/31523950", "http://www.ncbi.nlm.nih.gov/pubmed/20095914", "http://www.ncbi.nlm.nih.gov/pubmed/23231526", "http://www.ncbi.nlm.nih.gov/pubmed/23835333", "http://www.ncbi.nlm.nih.gov/pubmed/24517093", "http://www.ncbi.nlm.nih.gov/pubmed/21719095" ], "ideal_answer": [ "Yes, teplizumab is promising for diabetes prevention." ], "exact_answer": "yes", "type": "yesno", "id": "5e30f638fbd6abf43b000045", "snippets": [ { "offsetInBeginSection": 2377, "offsetInEndSection": 2474, "text": "Anti-CD3 teplizumab and anti-CD3 otelixizumab have been shown to provide C-peptide preservation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25941654", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1284, "text": "Underway are secondary prevention studies with teplizumab and with abatacept.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23231526", "endSection": "abstract" }, { "offsetInBeginSection": 2371, "offsetInEndSection": 2731, "text": "INTERPRETATION: Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in \u03b2-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21719095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Teplizumab therapy for type 1 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20095914", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Teplizumab for treatment of type 1 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968521", "endSection": "title" }, { "offsetInBeginSection": 775, "offsetInEndSection": 950, "text": "TAKE HOME MESSAGE\n\nIn Phase I/II randomized control trials, in patients with new onset T1D, teplizumab slowed the rate of loss of beta-cell function over 2 years of follow-up.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20095914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Teplizumab for treatment of type 1 diabetes (Prot\u00e9g\u00e9 study): 1-year results from a randomised, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21719095", "endSection": "title" }, { "offsetInBeginSection": 2377, "offsetInEndSection": 2737, "text": "INTERPRETATION\n\nFindings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in \u03b2-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21719095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Treatment of new onset type 1 diabetes with teplizumab: successes and pitfalls in development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517093", "endSection": "title" }, { "offsetInBeginSection": 761, "offsetInEndSection": 983, "text": "AREAS COVERED\n\nIn this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug's postulated mechanism of action and the identification of responders to therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517093", "endSection": "abstract" }, { "offsetInBeginSection": 1783, "offsetInEndSection": 1906, "text": "CONCLUSIONS Teplizumab is an anti-CD3 human monoclonal antibody with promising activity in treatment of patients with T1DM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22968521", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 891, "text": "The results from the TN-10 teplizumab prevention trial show that the diagnosis of type 1 diabetes can be delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people at high risk for disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31533907", "endSection": "abstract" }, { "offsetInBeginSection": 2377, "offsetInEndSection": 2737, "text": "INTERPRETATION\nFindings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in \u03b2-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21719095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23835333", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086558", "endSection": "title" }, { "offsetInBeginSection": 672, "offsetInEndSection": 883, "text": "The results from the TN-10 teplizumab prevention trial show that the diagnosis of type 1 diabetes can be delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people at high risk for disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31533907", "endSection": "abstract" }, { "offsetInBeginSection": 2343, "offsetInEndSection": 2687, "text": "Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in \u03b2-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21719095", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 571, "text": "Despite decades of research and clinical trials, no treatment exists yet to prevent or cure T1D. A recent prevention trial using the anti-CD3 antibody teplizumab in individuals at a high risk of developing T1D has provided the first piece of evidence that a safe and transient intervention may be able to delay disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31523950", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 953, "text": "In this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug's postulated mechanism of action and the identification of responders to therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7\u00a0years from diagnosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30569273", "endSection": "title" } ] }, { "body": "What is another name for acid sphingomyelinase deficiency (ASMD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27884455", "http://www.ncbi.nlm.nih.gov/pubmed/28259515", "http://www.ncbi.nlm.nih.gov/pubmed/27340749", "http://www.ncbi.nlm.nih.gov/pubmed/28801223", "http://www.ncbi.nlm.nih.gov/pubmed/22614361", "http://www.ncbi.nlm.nih.gov/pubmed/30795770", "http://www.ncbi.nlm.nih.gov/pubmed/27198631", "http://www.ncbi.nlm.nih.gov/pubmed/28228103", "http://www.ncbi.nlm.nih.gov/pubmed/26049896", "http://www.ncbi.nlm.nih.gov/pubmed/31080679" ], "ideal_answer": [ "Acid sphingomyelinase deficiency(ASMD) is also known as Niemann-Pick disease type A and type B.", "Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). The clinical spectrum distinguishes a severe infantile neurological form (type A), a non-neurological visceral form (type B) and a rare intermediate neurovisceral form.", "Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B)", "niemann-pick disease" ], "exact_answer": [ "Niemann-Pick disease type A and type B" ], "type": "factoid", "id": "5e36dc8cb5b409ea5300000d", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 276, "text": "Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27884455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Acid sphingomyelinase deficiency (ASMd, Niemann-Pick disease A/B)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28259515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an autosomal recessive genetic disorder caused by different SMPD1 mutations. Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28228103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "Acid sphingomyelinase (ASM) deficient Niemann-Pick disease is a lysosomal storage disorder resulting from mutations in the SMPD1 gene. The clinical spectrum distinguishes a severe infantile neurological form (type A), a non-neurological visceral form (type B) and a rare intermediate neurovisceral form. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28801223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "BACKGROUND\n\nAcid sphingomyelinase deficiency (ASMD), [Niemann-Pick Disease Types A and B (NPD A and B)], is an inherited metabolic disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27198631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Introduction\n\nAcid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick Type A and Type B disease) is a rare, inherited metabolic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31080679", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 255, "text": "Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28228103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Niemann-Pick disease (types A and B), or acid sphingomyelinase deficiency, is an inherited deficiency of acid sphingomyelinase, resulting in intralysosomal accumulation of sphingomyelin in cells throughout the body, particularly within those of the reticuloendothelial system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22614361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27884455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick Type A and Type B disease) is a rare, inherited metabolic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31080679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Acid sphingomyelinase deficiency (ASMD), due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is divided into infantile neurovisceral ASMD (Niemann-Pick type A), chronic neurovisceral ASMD (intermediate form, Niemann-Pick type A/B) and chronic visceral ASMD (Niemann-Pick type B).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30795770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Acid sphingomyelinase deficiency (ASMD), [Niemann-Pick Disease Types A and B (NPD A and B)], is an inherited metabolic disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27198631", "endSection": "abstract" } ] }, { "body": "What rare disease is associated with a mutation in the GPC6 gene on chromosome 13?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24458798", "http://www.ncbi.nlm.nih.gov/pubmed/19481194" ], "ideal_answer": [ " The proband had normal molecular analysis of the glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia", "The proband had normal molecular analysis of the glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia", "The glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia.", "Omodysplasia is a rare autosomal recessive disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in the GPC6 gene on chromosome 13." ], "exact_answer": [ "omodysplasia" ], "type": "factoid", "id": "5e3da25848dab47f26000004", "snippets": [ { "offsetInBeginSection": 215, "offsetInEndSection": 368, "text": " The proband had normal molecular analysis of the glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24458798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Mutations in the heparan-sulfate proteoglycan glypican 6 (GPC6) impair endochondral ossification and cause recessive omodysplasia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19481194", "endSection": "title" }, { "offsetInBeginSection": 511, "offsetInEndSection": 817, "text": "We now report that autosomal-recessive omodysplasia, a genetic condition characterized by short-limbed short stature, craniofacial dysmorphism, and variable developmental delay, maps to chromosome 13 (13q31.1-q32.2) and is caused by point mutations or by larger genomic rearrangements in glypican 6 (GPC6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19481194", "endSection": "abstract" } ] }, { "body": "What are 3 symptoms of Waardenburg Syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6791571", "http://www.ncbi.nlm.nih.gov/pubmed/29630160", "http://www.ncbi.nlm.nih.gov/pubmed/28544110", "http://www.ncbi.nlm.nih.gov/pubmed/30394532", "http://www.ncbi.nlm.nih.gov/pubmed/29158168" ], "ideal_answer": [ "Waardenburg syndrome is a rare genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation.", "Waardenburg syndrome (WS) is a rare autosomal dominant disorder characterized by dystopia canthorum, auditory, pigmentary abnormalities, and sensorineural deafness.", "Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation." ], "exact_answer": [ [ "hearing loss" ], [ "dystopia canthorum" ], [ "abnormal iris pigmentation" ] ], "type": "list", "id": "5e360f3d158f994d3a000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29158168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Waardenburg Syndrome (WS) is a condition characterized by pigmentary changes of the hair or skin, hearing loss, heterochromia iridis, and dystopia canthorum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29630160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Waardenburg syndrome (WS) is a disorder of neural crest cell migration characterized by auditory and pigmentary abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28544110", "endSection": "abstract" } ] }, { "body": "Does ProSavin use an adenoviral vector?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30156440" ], "ideal_answer": [ "No, ProSavin is a lentiviral vector based gene therapy." ], "exact_answer": "no", "type": "yesno", "id": "5e2dfab2fbd6abf43b00001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156440", "endSection": "title" }, { "offsetInBeginSection": 219, "offsetInEndSection": 466, "text": "ProSavin, a lentiviral vector based gene therapy that delivers local and continuous dopamine, was previously shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156440", "endSection": "abstract" } ] }, { "body": "Does radiation for tinea capitis increases brain tumor risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1640715", "http://www.ncbi.nlm.nih.gov/pubmed/15799699", "http://www.ncbi.nlm.nih.gov/pubmed/18447746", "http://www.ncbi.nlm.nih.gov/pubmed/11538033", "http://www.ncbi.nlm.nih.gov/pubmed/23227384", "http://www.ncbi.nlm.nih.gov/pubmed/8315464", "http://www.ncbi.nlm.nih.gov/pubmed/8081035", "http://www.ncbi.nlm.nih.gov/pubmed/11949834", "http://www.ncbi.nlm.nih.gov/pubmed/15565500", "http://www.ncbi.nlm.nih.gov/pubmed/6930522", "http://www.ncbi.nlm.nih.gov/pubmed/213536", "http://www.ncbi.nlm.nih.gov/pubmed/2137438" ], "ideal_answer": [ "Yes, radiation therapy for tinea capitis is associated with increased risk of meningiomas and gliomas." ], "exact_answer": "yes", "type": "yesno", "id": "5e3238bcfbd6abf43b000056", "snippets": [ { "offsetInBeginSection": 564, "offsetInEndSection": 763, "text": "Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18447746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "It is well known that radiation can induce meningiomas. These tumors usually arise in patients with a history of low-dose radiation to the scalp for treatment of tinea capitis or high-dose radiation for a previous brain tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565500", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 675, "text": "This paper describes six cases of radiation-associated intracranial meningiomas in patients previously treated with low-dose radiation to the scalp for tinea capitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565500", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 1008, "text": "After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15799699", "endSection": "abstract" }, { "offsetInBeginSection": 1078, "offsetInEndSection": 1340, "text": "The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15799699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Although meningiomas are known to be induced by low doses of cranial irradiation, such as those given to treat tinea capitis, little experience has been reported on the induction of meningiomas by high-dose cranial irradiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8315464", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 910, "text": "The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11538033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 378, "text": "We have analyzed 60 cases of intra-axial brain tumors associated with antecedent radiation therapy. These include four new cases. The patients had originally received radiation therapy for three reasons: (a) cranial irradiation for acute lymphoblastic leukemia (ALL), (b) definitive treatment of CNS neoplasia, and (c) treatment of benign disease (mostly cutaneous infections). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2137438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15799699", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Benign and malignant thyroid neoplasms after childhood irradiation for tinea capitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6930522", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 453, "text": "There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/213536", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 676, "text": "This paper describes six cases of radiation-associated intracranial meningiomas in patients previously treated with low-dose radiation to the scalp for tinea capitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565500", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 227, "text": "These tumors usually arise in patients with a history of low-dose radiation to the scalp for treatment of tinea capitis or high-dose radiation for a previous brain tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15565500", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 453, "text": "There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/213536", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 689, "text": "In addition to high dose radiation-induced meningiomas, intracranial meningiomas were observed in patients who underwent low-dose radiation for tinea capitis in childhood, applied en mass to immigrants coming to Israel from the North Africa and the Middle East during the 1950.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11949834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "A 39-year-old male developed primary brain lymphoma 33 years after receiving scalp irradiation for tinea capitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1640715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Secondary glioblastoma multiforme (sGBM) can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227384", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 624, "text": "The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8081035", "endSection": "abstract" } ] }, { "body": "What gene is mutated in Huntington's Disease patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27221146", "http://www.ncbi.nlm.nih.gov/pubmed/12046502", "http://www.ncbi.nlm.nih.gov/pubmed/28986324", "http://www.ncbi.nlm.nih.gov/pubmed/30850940", "http://www.ncbi.nlm.nih.gov/pubmed/26369532", "http://www.ncbi.nlm.nih.gov/pubmed/28817209", "http://www.ncbi.nlm.nih.gov/pubmed/24296361", "http://www.ncbi.nlm.nih.gov/pubmed/29178352", "http://www.ncbi.nlm.nih.gov/pubmed/17503740", "http://www.ncbi.nlm.nih.gov/pubmed/9392570", "http://www.ncbi.nlm.nih.gov/pubmed/8774958", "http://www.ncbi.nlm.nih.gov/pubmed/29172480", "http://www.ncbi.nlm.nih.gov/pubmed/23223017", "http://www.ncbi.nlm.nih.gov/pubmed/25416977", "http://www.ncbi.nlm.nih.gov/pubmed/11723754" ], "ideal_answer": [ "Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene HTT encoding the Huntingtin protein on chromosome 4.", "Huntington's disease (HD; OMIM 143100), a progressive neurodegenerative disorder, is caused by an expanded trinucleotide CAG (polyQ) motif in the huntingtin gene.", "(HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene.", "Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene." ], "exact_answer": [ "HTT gene encoding the protein huntingtin" ], "type": "factoid", "id": "5e31cb85fbd6abf43b00004e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28817209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT). PolyQ expansion promotes misfolding and aggregation of mutant HTT (mHTT) within neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28986324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29172480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Two decades ago, researchers identified that a CAG expansion mutation in the huntingtin (HTT) gene was involved in the pathogenesis of Huntington's disease (HD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29178352", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 326, "text": "However, since the identification of the HTT gene, there has been no advance in the development of therapeutic strategies to prevent or reduce the progression of HD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29178352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Mutations in the HTT gene , consisting of expansion of CAG triplets , cause the Huntington 's disease ( HD) , one of the major neurodegenerative disorders . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30850940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Huntington 's disease is a neurodegenerative disorder of the brain that is caused by the mutation of the gene which produces a protein called huntingtin ( htt) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25416977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Huntington 's disease ( HD ) is an autosomal dominant neurodegenerative disorder of the central nervous system ( CNS ) that is defined by a CAG expansion in exon 1 of the huntingtin gene leading to the production of mutant huntingtin ( mHtt) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27221146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A mutation in the huntingtin ( Htt ) gene produces mutant Htt and Huntington 's disease ( HD) , a neurodegenerative disorder . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23223017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Huntington 's disease ( HD ) is a devastating neurodegenerative disorder that occurs in patients with a mutation in the huntingtin or IT15 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17503740", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Huntington's disease is an inherited disorder caused by expanded stretch of consecutive trinucleotides (cytosine-adenosine-guanine, CAG) within the first exon of the huntingtin (HTT) gene on chromosome 4 (p16.3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24296361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Huntington's disease is an inherited disorder caused by expansion of a CAG trinucleotide repeat in the IT15 gene, which leads to expansion of a polyglutamine tract within the protein called huntingtin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9392570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by high instability and extension of CAG sequences within the coding region of IT15 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12046502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Huntington's disorder (HD), caused by mutations of the IT-15 gene, is an autosomal genetic disease that causes the breakdown of the nerve cells in the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26369532", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 624, "text": "Huntington's disease is caused by an expanded trinucleotide CAG repeat in the HD gene on chromosome 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11723754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Positional cloning has shown that the Huntington disease (HD) mutation is an expanded trinucleotide repeat in the IT15 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8774958", "endSection": "abstract" } ] }, { "body": "List types of cancer where Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28408616", "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "http://www.ncbi.nlm.nih.gov/pubmed/30367041" ], "ideal_answer": [ "Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved in the development of pancreatic cancer, glioblastoma and breast cancer.", "Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) has been implicated in various types of cancer such as glioblastoma, breast cancer and pancreatic cancer.", "Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved in several types of cancer including pancreatic cancer, glioblastoma and breast cancer." ], "exact_answer": [ [ "Glioblastoma" ], [ "Breast cancer" ], [ "Pancreatic cancer" ] ], "type": "list", "id": "5e493bc06d0a277941000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367041", "endSection": "title" }, { "offsetInBeginSection": 470, "offsetInEndSection": 1111, "text": "We identify an 87-amino-acid peptide encoded by the circular form of the long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) that suppresses glioblastoma cell proliferation in vitro and in vivo. This peptide directly interacts with polymerase associated factor complex (PAF1c) and inhibits the transcriptional elongation of multiple oncogenes. The expression of this peptide and its corresponding circRNA are decreased in glioblastoma compared with the levels in normal tissues. Our results establish the existence of peptides encoded by circRNAs and demonstrate their potential functions in glioblastoma tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30367041", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 887, "text": "Breast cancer is a heterogeneous and polygenic disease that can be divided into different molecular subtypes based on histological and genomic features. To date, numerous susceptibility loci of breast cancer have been discovered by genome-wide association studies and may expand the genetic features. However, few loci have been further studied according to molecular subtypes.MATERIALS AND METHODS: We genotyped 23 recently discovered single nucleotide polymorphisms using the Sequenom iPLEX platform in a female Chinese cohort of 3,036 breast cancer patients (2,935 samples matched molecular subtypes) and 3,036 healthy controls.RESULTS: Through a stratification analysis, 5q11.2/MAP3K1 (rs16886034, rs16886364, rs16886397, rs1017226, rs16886448) and 7q32.3/LINC-PINT (rs4593472) were associated with Luminal A, and 10q26.1/FGFR2 (rs35054928) was associated with Luminal B.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28408616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for pancreatic cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1170, "text": "Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a long noncoding RNA (lncRNA) that regulates tumor cell viability and proliferation. We used qRT-PCR and RNA FISH analysis to evaluate Linc-pint levels in the plasma and tumor tissues of pancreatic cancer (PCa) patients. Our data demonstrate that Linc-pint expression is lower in plasma samples from PCa patients than from healthy individuals, and indicate that plasma Linc-pint levels are more sensitive than CA19-9 for detecting PCa. Our data also show that Linc-pint levels are lower in PCa tumors than in adjacent tissues, carcinoma of the ampulla of Vater (CAV) and cholangiocarcinoma (CCA), and suggest that Linc-pint could be used for distinguishing the cause of malignant obstructive jaundice. Low plasma Linc-pint levels correlate with tumor recurrence, while low tumor Linc-pint levels correlate with poor prognosis for PCa patients after pancreatectomy. These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708234", "endSection": "abstract" } ] }, { "body": "Is pimavanserin a typical antipsychotic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29047301" ], "ideal_answer": [ "No, pimavanserin is an atypical antipsychotic." ], "exact_answer": "no", "type": "yesno", "id": "5e2dbd0afbd6abf43b000017", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 193, "text": "Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29047301", "endSection": "abstract" } ] }, { "body": "Can Flotillin be used as exosomal marker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22221959", "http://www.ncbi.nlm.nih.gov/pubmed/26420226" ], "ideal_answer": [ "Yes,\nFlotillin 1 is a known exosomal marker protein." ], "exact_answer": "yes", "type": "yesno", "id": "5e5b93a2752ebcdc7a000003", "snippets": [ { "offsetInBeginSection": 1151, "offsetInEndSection": 1237, "text": "Flotillin 1 and tumor susceptibility gene 101 (TSG101), two exosomal marker proteins, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22221959", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 659, "text": "expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26420226", "endSection": "abstract" } ] }, { "body": "How many genes belong to the KRAB-ZNF family in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19695231", "http://www.ncbi.nlm.nih.gov/pubmed/23253430", "http://www.ncbi.nlm.nih.gov/pubmed/17038565", "http://www.ncbi.nlm.nih.gov/pubmed/30444046", "http://www.ncbi.nlm.nih.gov/pubmed/29198826", "http://www.ncbi.nlm.nih.gov/pubmed/20573777" ], "ideal_answer": [ "The KRAB-ZNF family is a multisubunit protein family comprised of 70 co-regulated genes, denoted KLR1-ZNF15, that is represented by multigene families in the human genome.", "There are 70 human KRAB-ZNFs." ], "exact_answer": [ "70" ], "type": "factoid", "id": "5d31b847b3a6380763000002", "snippets": [ { "offsetInBeginSection": 344, "offsetInEndSection": 476, "text": "By mammalian one- or two-hybrid experiments in HEK293 cells, we compared transcriptional repression activities of 61 human KRAB-ZNFs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19695231", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 694, "text": "Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198826", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 841, "text": " High-resolution mapping on human chromosome 19 revealed that CBX1 coats large domains 0.1-4 Mb in size, which coincide with the position of KRAB-ZNF gene clusters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17038565", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 513, "text": "Here, we examine the structural and functional diversity of the 70 human KRAB-ZNF genes involved in the most recent primate SD events including genes that arose in the hominid lineag", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573777", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 754, "text": " Here, we discuss the main evolutionary and molecular features that make transcription factors (TFs), especially the family of zinc finger proteins with a Kr\u00fcppel-associated box domain (KRAB-ZNF), strong candidates to play an important role in postzygotic reproductive isolation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23253430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The KRAB-ZNF (Kr\u00fcppel-associated box domain zinc finger) gene family is composed of a large number of highly homologous genes, gene isoforms, and pseudogenes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30444046", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by Asciminib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30927708", "http://www.ncbi.nlm.nih.gov/pubmed/28329763", "http://www.ncbi.nlm.nih.gov/pubmed/29568367", "http://www.ncbi.nlm.nih.gov/pubmed/31826340", "http://www.ncbi.nlm.nih.gov/pubmed/31006307", "http://www.ncbi.nlm.nih.gov/pubmed/29325229", "http://www.ncbi.nlm.nih.gov/pubmed/31543464", "http://www.ncbi.nlm.nih.gov/pubmed/30059193", "http://www.ncbi.nlm.nih.gov/pubmed/29522367", "http://www.ncbi.nlm.nih.gov/pubmed/30137981" ], "ideal_answer": [ "Asciminib is an orally administered allosteric inhibitor of the BCR-ABL tyrosine kinase." ], "exact_answer": [ "BCR-ABL tyrosine kinase" ], "type": "factoid", "id": "5e30e80bfbd6abf43b00003b", "snippets": [ { "offsetInBeginSection": 1091, "offsetInEndSection": 1265, "text": "Asciminib, an allosteric ABL1 inhibitor, could demonstrate a higher capacity in overcoming common TKIs resistant mutations, including T315I, but clinical findings are needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522367", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 473, "text": "Moreover, allosteric targeting has been identified to consequentially inhibit Bcr-Abl activity, which led to the recent development of ABL-001 (asciminib) that selectively binds the myristoyl pocket.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29325229", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Asciminib (previously ABL001), which binds the myristate-binding pocket of the Bcr-Abl kinase domain, is in phase I clinical trials as monotherapy and in combination with imatinib, nilotinib and dasatinib for the treatment of patients with refractory CML or Ph+ ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Asciminib (ABL001) is an orally administered allosteric inhibitor of the BCR-ABL tyrosine kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30059193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137981", "endSection": "title" }, { "offsetInBeginSection": 321, "offsetInEndSection": 548, "text": "We describe the discovery of asciminib (ABL001), the first allosteric BCR-ABL1 inhibitor to reach the clinic. Asciminib binds to the myristate pocket of BCR-ABL1 and maintains activity against TKI-resistant ATP-site mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137981", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 865, "text": "Here we characterize ABL001 (asciminib), a potent and selective allosteric ABL1 inhibitor that is undergoing clinical development testing in patients with CML and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28329763", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 430, "text": "We describe the discovery of asciminib (ABL001), the first allosteric BCR-ABL1 inhibitor to reach the clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137981", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 547, "text": "Asciminib binds to the myristate pocket of BCR-ABL1 and maintains activity against TKI-resistant ATP-site mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31006307", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Asciminib ( previously ABL001) , which binds the myristate-binding pocket of the Bcr-Abl kinase domain , is in phase I clinical trials as monotherapy and in combination with imatinib , nilotinib and dasatinib for the treatment of patients with refractory CML or Ph+ ALL . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Asciminib is an allosteric inhibitor that binds a myristoyl site of the BCR-ABL1 protein , locking BCR-ABL1 into an inactive conformation through a mechanism distinct from those for all other ABL kinase inhibitors . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31826340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Discovery of Asciminib ( ABL001) , an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1 .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137981", "endSection": "title" }, { "offsetInBeginSection": 431, "offsetInEndSection": 548, "text": "Asciminib binds to the myristate pocket of BCR-ABL1 and maintains activity against TKI-resistant ATP-site mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137981", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 431, "text": "We describe the discovery of asciminib (ABL001), the first allosteric BCR-ABL1 inhibitor to reach the clinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30137981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Asciminib (previously ABL001), which binds the myristate-binding pocket of the Bcr-Abl kinase domain, is in phase I clinical trials as monotherapy and in combination with imatinib, nilotinib and dasatinib for the treatment of patients with refractory CML or Ph+ ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Asciminib, a highly selective non-ATP competitive inhibitor of BCR-ABL, has demonstrated to be a promising drug for patients with chronic myeloid leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30927708", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 720, "text": "The obtained results indicate that the mutations have adversely influence on the binding of Asciminib to BCR-ABL, as the nonpolar contributions decline in the two mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30927708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Asciminib is a potent, specific BCR-ABL1 inhibitor being developed for the treatment of patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph\u2009+\u2009ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31006307", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 530, "text": "Asciminib, an allosteric inhibitor targeting the myristoyl-binding pocket of BCR-ABL1, is active against most single mutants but ineffective against all tested compound mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31543464", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 831, "text": "Here we characterize ABL001 (asciminib), a potent and selective allosteric ABL1 inhibitor that is undergoing clinical development testing in patients with CML and Philadelphia chromosome-positive (Ph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28329763", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1251, "text": "Asciminib, an allosteric ABL1 inhibitor, could demonstrate a higher capacity in overcoming common TKIs resistant mutations, including T315I, but clinical findings are needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522367", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 529, "text": "Asciminib, an allosteric inhibitor targeting the myristoyl-binding pocket of BCR-ABL1, is active against most single mutants but ineffective against all tested compound mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31543464", "endSection": "abstract" } ] }, { "body": "Please list 2 human diseases caused by a coronavirus.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29896174", "http://www.ncbi.nlm.nih.gov/pubmed/24769571", "http://www.ncbi.nlm.nih.gov/pubmed/26290414", "http://www.ncbi.nlm.nih.gov/pubmed/27840203", "http://www.ncbi.nlm.nih.gov/pubmed/28616501", "http://www.ncbi.nlm.nih.gov/pubmed/28466096", "http://www.ncbi.nlm.nih.gov/pubmed/28220326", "http://www.ncbi.nlm.nih.gov/pubmed/28643204", "http://www.ncbi.nlm.nih.gov/pubmed/31226023" ], "ideal_answer": [ "Middle East respiratory syndrome (MERS) and SARS are diseases caused by a coronavirus.", "MERS and SARS are 2 human diseases caused by coronaviruses" ], "exact_answer": [ [ "MERS" ], [ "SARS" ] ], "type": "list", "id": "5e2f43bafbd6abf43b000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Since severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) share similar characteristics with respect to clinical signs, etiology, and transmission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28220326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 410, "text": "Human coronaviruses (hCoVs) can be divided into low pathogenic and highly pathogenic coronaviruses. The low pathogenic CoVs infect the upper respiratory tract and cause mild, cold-like respiratory illness. In contrast, highly pathogenic hCoVs such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) predominantly infect lower airways and cause fatal pneumon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28466096", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 306, "text": "In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31226023", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "First identified in 2012 , Middle East respiratory syndrome ( MERS ) is caused by an emerging human coronavirus , which is distinct from the severe acute respiratory syndrome coronavirus ( SARS-CoV) , and represents a novel member of the lineage C betacoronoviruses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26290414", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 365, "text": "The virus was termed Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and is taken notice of important coronavirus caused severe diseases to human after the outbreak of severe acute respiratory syndrome (SARS) coronavirus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24769571", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 321, "text": "They mostly cause enteric or respiratory disease, which can be severe and life threatening, e.g., in the case of the zoonotic coronaviruses causing severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28643204", "endSection": "abstract" } ] }, { "body": "What is characteristic to Fitz-Hugh\u2013Curtis syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19058334", "http://www.ncbi.nlm.nih.gov/pubmed/26774818", "http://www.ncbi.nlm.nih.gov/pubmed/6769152", "http://www.ncbi.nlm.nih.gov/pubmed/15725719", "http://www.ncbi.nlm.nih.gov/pubmed/11327124", "http://www.ncbi.nlm.nih.gov/pubmed/29284768", "http://www.ncbi.nlm.nih.gov/pubmed/30226491", "http://www.ncbi.nlm.nih.gov/pubmed/27094840", "http://www.ncbi.nlm.nih.gov/pubmed/29464468", "http://www.ncbi.nlm.nih.gov/pubmed/28057084", "http://www.ncbi.nlm.nih.gov/pubmed/29558895", "http://www.ncbi.nlm.nih.gov/pubmed/26601101", "http://www.ncbi.nlm.nih.gov/pubmed/29417387" ], "ideal_answer": [ "Fitz-Hugh-Curtis syndrome is a rare complication of pelvic inflammatory disease that involves liver capsule inflammation associated with genital tract infection, which is usually caused by Neisseria gonorrhoea and Chlamydia trachomatis." ], "type": "summary", "id": "5e30ec74fbd6abf43b00003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Fitz-Hugh-Curtis syndrome (FHCS) is characterized by perihepatic and pelvic inflammation and occurs mostly in women of childbearing age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29417387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Fitz-Hugh-Curtis syndrome (FHCS) is defined as inflammation on the surface of the liver following sexually transmitted chlamydia infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29464468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "BACKGROUND: Fitz-Hugh-Curtis syndrome or acute perihepatitis is considered a rare complication of pelvic inflammatory disease, mostly associated with chlamydial or gonococcal salpingitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29558895", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1311, "text": "Fitz-Hugh-Curtis syndrome (FHCS) is the inflammation of the hepatic capsule without affecting the parenchyma, which is associated with a pelvic inflammatory disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30226491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "BACKGROUND: Fitz-Hugh-Curtis syndrome is defined as perihepatitis associated with pelvic inflammatory disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28057084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "BACKGROUND Fitz-Hugh-Curtis (FHC) syndrome is a perihepatitis linked to inflammatory pelvic disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29284768", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 607, "text": "Fitz-Hugh-Curtis syndrome is a rare complication of pelvic inflammatory disease; it involves liver capsule inflammation associated with genital tract infection, which is usually caused by Neisseria gonorrhoea and Chlamydia trachomatis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26774818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Fitz-Hugh-Curtis syndrome has been defined as perihepatitis accompanying pelvic inflammatory disease caused by Neisseria gonorrhoeae and Chlamydia trachomatis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15725719", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1309, "text": "CONCLUSION\n\nFor women of childbearing age with acute pain in the upper right abdomen alone or together with pain in the lower abdomen, Fitz-Hugh-Curtis syndrome should be considered during differential diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19058334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND\n\nFitz-Hugh-Curtis syndrome or acute perihepatitis is considered a rare complication of pelvic inflammatory disease, mostly associated with chlamydial or gonococcal salpingitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29558895", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1311, "text": "Fitz-Hugh-Curtis syndrome (FHCS) is the inflammation of the hepatic capsule without affecting the parenchyma, which is associated with a pelvic inflammatory disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30226491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND Fitz-Hugh-Curtis syndrome is defined as perihepatitis associated with pelvic inflammatory disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28057084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "The Fitz-Hugh--Curtis syndrome is an extragenital manifestation of gonorrhea , characterized by fibrinous inflammation of the subphrenic area with violinstring-like adhesions between the liver surface and the parietal peritoneum . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6769152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Perihepatitis or Fitz-Hugh-Curtis syndrome is a complication of pelvic inflammatory disease that usually leaves characteristic violin string adhesions on the anterior liver surface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11327124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND\nFitz-Hugh-Curtis syndrome or acute perihepatitis is considered a rare complication of pelvic inflammatory disease, mostly associated with chlamydial or gonococcal salpingitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29558895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Fitz-Hugh-Curtis syndrome is characterized by an inflammation of the perihepatic capsules associated with pelvic inflammatory disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27094840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Fitz-Hugh-Curtis syndrome is a type of perihepatitis that causes liver capsular infection without infecting the hepatic parenchyma or pelvis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26601101", "endSection": "abstract" } ] }, { "body": "What is the trade name of sildenafil?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25984278" ], "ideal_answer": [ "The trade name of sildenafil is Viagra." ], "exact_answer": [ "Viagra" ], "type": "factoid", "id": "5e499e266d0a27794100000c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 289, "text": "Chronic drug abuse and sexual dysfunction specifically erectile dysfunction may lead drug abusers to seek over-the-counter or non-prescription medications, out of which Sildenafil citrate, sold as the trade name of Viagra\u00ae can be considered as a prime and important treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25984278", "endSection": "abstract" } ] }, { "body": "How large is the SARS-CoV proteome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15253436", "http://www.ncbi.nlm.nih.gov/pubmed/17520018" ], "ideal_answer": [ "The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products." ], "exact_answer": [ "The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products." ], "type": "factoid", "id": "5e5b6f04b761aafe0900000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17520018", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 587, "text": "For the first time, all of the four predicted structural proteins of SARS-CoV were identified, including S (Spike), M (Membrane), N (Nucleocapsid), and E (Envolope) proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15253436", "endSection": "abstract" } ] }, { "body": "Is Apremilast effective for Beh\u00e7et\u2019s Syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31722152", "http://www.ncbi.nlm.nih.gov/pubmed/27163156", "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "http://www.ncbi.nlm.nih.gov/pubmed/31609785" ], "ideal_answer": [ "Yes, Apremilast is effective for Behcet's Syndrome" ], "exact_answer": "yes", "type": "yesno", "id": "5e30f417fbd6abf43b000043", "snippets": [ { "offsetInBeginSection": 386, "offsetInEndSection": 686, "text": "AREAS COVERED: This review provides a digest of all current experience and evidence about pharmacological agents recently described as having a role in the treatment of BS, including interleukin (IL)-1 inhibitors, tocilizumab, rituximab, alemtuzumab, ustekinumab, interferon-alpha-2a, and apremilast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27163156", "endSection": "abstract" }, { "offsetInBeginSection": 1725, "offsetInEndSection": 1846, "text": "CONCLUSIONS\n\nApremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 1719, "offsetInEndSection": 1839, "text": "CONCLUSIONS Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 1725, "offsetInEndSection": 1846, "text": "CONCLUSIONS\nApremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 1692, "offsetInEndSection": 1800, "text": "Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875256", "endSection": "abstract" }, { "offsetInBeginSection": 1848, "offsetInEndSection": 2080, "text": "In patients with oral ulcers associated with Beh\u00e7et's syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache. (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31722152", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 563, "text": "Apremilast is now approved for the treatment of oral ulcer of Beh\u00e7et syndrome in the United States.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31609785", "endSection": "abstract" } ] }, { "body": "Is Rad4/XPC a DNA damage sensing protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27035942", "http://www.ncbi.nlm.nih.gov/pubmed/27720644", "http://www.ncbi.nlm.nih.gov/pubmed/26422135", "http://www.ncbi.nlm.nih.gov/pubmed/25562780", "http://www.ncbi.nlm.nih.gov/pubmed/29283431", "http://www.ncbi.nlm.nih.gov/pubmed/17882165" ], "ideal_answer": [ "Yes,\r\nDNA damage recognition is achieved by the Rad4/XPC nucleotide excision repair complex." ], "exact_answer": "yes", "type": "yesno", "id": "5e46ece93f5415952900000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27035942", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Kinetic gating mechanism of DNA damage recognition by Rad4/XPC.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25562780", "endSection": "title" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1073, "text": " These findings indicate that the lesions recognized by Rad4/XPC thermodynamically destabilize the Watson-Crick double helix in a manner that facilitates the flipping-out of two base pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17882165", "endSection": "abstract" } ] }, { "body": "List symptoms of the Hakim Triad?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31417837", "http://www.ncbi.nlm.nih.gov/pubmed/25278622", "http://www.ncbi.nlm.nih.gov/pubmed/26222251", "http://www.ncbi.nlm.nih.gov/pubmed/23250022", "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "http://www.ncbi.nlm.nih.gov/pubmed/21194654" ], "ideal_answer": [ "Triad of Hakim is well known for normal pressure hydrocephalus (NPH) and includes dementia, gait disturbances and urinary incontinence." ], "exact_answer": [ [ "dementia" ], [ "gait disturbances" ], [ "urinary incontinence" ] ], "type": "list", "id": "5e2f9e0dfbd6abf43b000034", "snippets": [ { "offsetInBeginSection": 337, "offsetInEndSection": 471, "text": " It is characterised clinically by gait disturbance, cognitive dysfunction, and urinary incontinence (known as the Hakim-Adams triad).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "The definition of normal pressure hydrocephalus (NPH), in adults, associates clinical signs (Adams and Hakim triad) involving gait disorders, urinary incontinence and dementia, associated with aspects on brain imaging that are consistent with this hypothesis and also normal or slightly increased intracranial pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23250022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Normal pressure hydrocephalus is a frequently missed clinical entity with the typical symptom triad of gait disturbance, urinary incontinence and dementia (Hakim's triad) and occurs mostly from the 6th decade of life onwards. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25278622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "Normal pressure hydrocephalus (NPH) is a clinical triad of gait disturbance, dementia, and urinary incontinence combined with radiographic findings of ventriculomegaly and laboratory findings of normal cerebrospinal fluid pressures. Although it was first described by Hakim and Adams in 1965, there is no formal definition of NPH, causing discrepancy in its incidence in various studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21194654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 669, "text": "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 672, "text": "Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia , gait difficulty and urinary incontinence--have been published earlier , it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6583309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Triad of Hakim--Adams is well known for normal pressure hydrocephalus ( NPH): dementia , gait disturbances and urinary incontinence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Normal pressure hydrocephalus is a frequently missed clinical entity with the typical symptom triad of gait disturbance , urinary incontinence and dementia ( Hakim 's triad ) and occurs mostly from the 6th decade of life onwards", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25278622", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 654, "text": "Here , we report on an 83-year-old man presenting with mimic symptoms of idiopathic normal pressure hydrocephalus ( cognitive disorder , gait disturbance , and urinary urgency: Hakim 's triad ) because of obstructive hydrocephalus caused by a DVA located in the aqueduct", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31417837", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 643, "text": "Here, we report on an 83-year-old man presenting with mimic symptoms of idiopathic normal pressure hydrocephalus (cognitive disorder, gait disturbance, and urinary urgency: Hakim's triad) because of obstructive hydrocephalus caused by a DVA located in the aqueduct.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31417837", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 471, "text": "It is characterised clinically by gait disturbance, cognitive dysfunction, and urinary incontinence (known as the Hakim-Adams triad).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "The definition of normal pressure hydrocephalus (NPH), in adults, associates clinical signs (Adams and Hakim triad) involving gait disorders, urinary incontinence and dementia, associated with aspects on brain imaging that are consistent with this hypothesis and also normal or slightly increased intracranial pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23250022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21698923", "endSection": "abstract" } ] }, { "body": "Is the protein ABCG2 transmembrane?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30021380", "http://www.ncbi.nlm.nih.gov/pubmed/29514827", "http://www.ncbi.nlm.nih.gov/pubmed/29407974" ], "ideal_answer": [ "Yes,\nthe protein ABCG2 is transmembrane." ], "exact_answer": "yes", "type": "yesno", "id": "5e5b60adb761aafe0900000b", "snippets": [ { "offsetInBeginSection": 21, "offsetInEndSection": 74, "text": "the transmembrane ATP-binding cassette transporter G2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29407974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "ATP-binding cassette (ABC) transporters are transmembrane efflux transporters mediating the extrusion of an array of substrates ranging from amino acids and lipids to xenobiotics, and many therapeutic compounds, including anticancer drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The ATP-binding cassette (ABC) transporter family is a large class of ATP energy-dependent transmembrane proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30021380", "endSection": "abstract" } ] }, { "body": "Can radiotherapy cause radiation induced osteosarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27906102", "http://www.ncbi.nlm.nih.gov/pubmed/11449317", "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "http://www.ncbi.nlm.nih.gov/pubmed/27866298", "http://www.ncbi.nlm.nih.gov/pubmed/26009571", "http://www.ncbi.nlm.nih.gov/pubmed/20952292", "http://www.ncbi.nlm.nih.gov/pubmed/22908888", "http://www.ncbi.nlm.nih.gov/pubmed/23397792", "http://www.ncbi.nlm.nih.gov/pubmed/12199765", "http://www.ncbi.nlm.nih.gov/pubmed/29330865", "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "http://www.ncbi.nlm.nih.gov/pubmed/21523724", "http://www.ncbi.nlm.nih.gov/pubmed/1771248", "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "http://www.ncbi.nlm.nih.gov/pubmed/26927177", "http://www.ncbi.nlm.nih.gov/pubmed/8865500", "http://www.ncbi.nlm.nih.gov/pubmed/16855507", "http://www.ncbi.nlm.nih.gov/pubmed/23172499", "http://www.ncbi.nlm.nih.gov/pubmed/16434828", "http://www.ncbi.nlm.nih.gov/pubmed/27729091", "http://www.ncbi.nlm.nih.gov/pubmed/26605276" ], "ideal_answer": [ "Yes, Radiation-induced osteosarcomas are a recognized complication of radiation therapy." ], "exact_answer": "yes", "type": "yesno", "id": "5e3247f1fbd6abf43b00005b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "A case of radiation-induced osteosarcoma of the skull presenting as a cutaneous epidermotropic tumor with a short latent period.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330865", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Radiation-induced sarcoma (RIS) is an unusual but well documented tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330865", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 608, "text": "We report a case of a 34-year-old female who developed an osteosarcoma of the scalp, over a previous craniotomy scar, 3 years after excision of a frontal anaplastic oligodendroglioma which had been followed by a course of 6\u2009weeks radiotherapy (58\u2009Gy) and 6 cycles of temozolomide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Radiation-induced osteosarcoma after Gamma Knife surgery for vestibular schwannoma: a case report and literature review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27866298", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "We present a rare case of radiation-induced osteosarcoma following Gamma Knife\u00ae surgery (GKS) for a vestibular schwannoma (VS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27866298", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 621, "text": "The osteosarcoma was considered to be a radiation-induced malignancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27866298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Radiation-induced osteosarcoma of the maxilla and mandible after radiotherapy for nasopharyngeal carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729091", "endSection": "title" }, { "offsetInBeginSection": 175, "offsetInEndSection": 413, "text": "The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma (NPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729091", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 670, "text": "Of these patients, 47 who developed RISOM and met inclusion criteria were included in this study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729091", "endSection": "abstract" }, { "offsetInBeginSection": 1451, "offsetInEndSection": 1568, "text": "CONCLUSIONS: RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729091", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Radiation-induced osteosarcoma of the\u00a0skull base after radiation therapy in a patient with nasopharyngeal carcinoma: a\u00a0case report and review of the\u00a0literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906102", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND: Radiation-induced osteosarcomas are a recognized complication of radiation therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906102", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 455, "text": "CASE PRESENTATION: We describe a rare case of a patient with a skull base radiation-induced osteosarcoma treated 11\u00a0years before with ionizing radiation for an undifferentiated carcinoma of the nasopharynx. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906102", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 714, "text": "CONCLUSIONS: Radiation-induced osteosarcoma of the\u00a0skull base after treatment of nasopharyngeal carcinoma is a very rare but very aggressive complication with a poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27906102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Radiation-Associated Low-Grade Extraskeletal Osteosarcoma of the Neck Following Treatment for Thyroid Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009571", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Low-grade extraskeletal osteosarcoma is a rare tumor that may arise de novo or following radiation therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009571", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 962, "text": "While there is a report of a low-grade extraskeletal osteosarcoma arising following radiotherapy for a benign condition, to the best of our knowledge this is the first reported case of a low-grade extraskeletal osteosarcoma occurring following radiotherapy for thyroid cancer, and the only case reported in the soft tissue of the head and neck region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009571", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 405, "text": "Here we a report a case of radiation induced osteosarcoma which developed 11\u2009years after a single fraction of 700\u2009cGy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Osteosarcoma following single fraction radiation prophylaxis for heterotopic ossification.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908888", "endSection": "title" }, { "offsetInBeginSection": 539, "offsetInEndSection": 644, "text": "The radiotherapy dose for this patient is lower than classically reported for radiation induced sarcomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908888", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 888, "text": "The latency period between radiotherapy and osteosarcoma onset was 1.3 years shorter inside than outside the radiation field.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11449317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Osteosarcoma after radiotherapy for prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20952292", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Osteosarcoma after external beam radiation therapy for recurrent choroidal melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16855507", "endSection": "title" }, { "offsetInBeginSection": 647, "offsetInEndSection": 747, "text": "Diagnostic criteria were fulfilled and the lesion was classified as a radiation induced osteosarcoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23397792", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 200, "text": "Although a rare complication of ionizing radiation, radiation-induced osteosarcoma is now more frequently recognized as radiation therapy has become common and cancer survival has increased", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21523724", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 404, "text": "Here we a report a case of radiation induced osteosarcoma which developed 11 years after a single fraction of 700 cGy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22908888", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 917, "text": "Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Osteosarcoma following radiotherapy: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1771248", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Radiation-induced fibrosarcoma after radiotherapy for osteosarcoma in the mandibular condyle.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23172499", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Post-radiation osteosarcoma of the scapula.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8865500", "endSection": "title" }, { "offsetInBeginSection": 103, "offsetInEndSection": 248, "text": "Radiation-induced osteosarcomas generally occur 3-30 years after exposure and are most common after radiotherapy for cervical or breast carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8865500", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 325, "text": "Radiation-induced osteosarcoma is one of the rare types of radiation-induced sarcomas , with the risk of radiation-induced osteosarcomas being only 0.01 % -0.03 % among all patients treated with radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 827, "text": "Radiation-induced osteosarcoma is a well-known but rare complication of radiotherapy for brain neoplasms with a poor prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16434828", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 979, "text": "The prognosis of patients developing osteosarcoma after radiotherapy for prostate cancer is similar to other radiation-induced osteosarcomas occurring in the axial skeleton , with a 50 % overall mortality within the first year after diagnosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20952292", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 924, "text": "Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "endSection": "abstract" }, { "offsetInBeginSection": 67, "offsetInEndSection": 237, "text": "Twenty-seven years 11 months after orthovoltage radiotherapy of the right breast a 69-year-old woman developed a radiation-induced osteosarcoma of the right thoracic wall", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12199765", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 563, "text": "We report a case of radiation-induced osteosarcoma developed from skull after 7 years of craniospinal radiotherapy for pineoblastoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26605276", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 730, "text": "Although the concepts of direct and indirect effects of radiation are fully applicable to low-LET ( linear energy transfer ) radioresistant tumor cells/normal tissues such as osteosarcoma cells and chondrocytes , it is believed that radiation-associated damage to DNA does not play a major role in the mechanism of cell death in low-LET radiosensitive tumors/normal tissues such as malignant lymphoma cells and lymphocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927177", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1560, "text": "From these clinicopathological findings, both cases were diagnosed as radiation-induced osteosarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 292, "text": "Here we report two cases of radiation-induced osteosarcoma in the paranasal sinus after treatment for frontal glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "endSection": "abstract" }, { "offsetInBeginSection": 1668, "offsetInEndSection": 1864, "text": "As the prognosis of radiation-induced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1668, "text": "Radiation-induced osteosarcomas appeared 16 and 12 years after radiotherapy in cases 1 and 2, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Most radiation-induced osteosarcomas of the skull are reported to arise in the facial bone or paranasal sinus after radiotherapy for retinoblastoma and/or pituitary adenoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Radiation-induced osteosarcomas after treatment for frontal gliomas: a report of two cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Radiation-induced osteosarcoma of the skull mimicking cutaneous tumor after treatment for frontal glioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "title" }, { "offsetInBeginSection": 117, "offsetInEndSection": 322, "text": "Radiation-induced osteosarcoma is one of the rare types of radiation-induced sarcomas, with the risk of radiation-induced osteosarcomas being only 0.01%-0.03% among all patients treated with radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Radiation-induced sarcomas are recognized complications of radiation therapy and are associated with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 430, "text": "There have been only four reported cases of radiation-induced osteosarcomas after radiotherapy for gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 571, "text": "Here, we report a unique case of radiation-induced osteosarcomas arising on the skull and extending to the skin, with a short latent period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND\nThe increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible (RIOSM) has become a significant problem that can limit long-term survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27729091", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1031, "text": "In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 918, "text": "Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 250, "text": "A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Osteosarcoma is one of the neoplasms that may occur following exposure to radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "endSection": "abstract" }, { "offsetInBeginSection": 1668, "offsetInEndSection": 1863, "text": "As the prognosis of radiation-induced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21046312", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 409, "text": "This report describes the late recurrence of choroidal melanoma and subsequent radiation-induced osteosarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16855507", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 321, "text": "Radiation-induced osteosarcoma is one of the rare types of radiation-induced sarcomas, with the risk of radiation-induced osteosarcomas being only 0.01%-0.03% among all patients treated with radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 429, "text": "There have been only four reported cases of radiation-induced osteosarcomas after radiotherapy for gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 1380, "offsetInEndSection": 1594, "text": "Although radiation-induced osteosarcoma is an uncommon but dire complication of radiotherapy, its incidence will probably increase in the future as the frequency of radiation treatment and cancer survival increase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21523724", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 556, "text": "We report a case of radiation-induced osteosarcoma developed from skull after 7 years of craniospinal radiotherapy for pineoblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26605276", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 971, "text": "The prognosis of patients developing osteosarcoma after radiotherapy for prostate cancer is similar to other radiation-induced osteosarcomas occurring in the axial skeleton, with a 50% overall mortality within the first year after diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20952292", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 1048, "text": "To our knowledge the only other case report of post-radiation osteosarcoma with a short latency period was a case of osteosarcoma in the craniofacial bone 3 years after radiotherapy for maxillary squamous cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330865", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 570, "text": "Here, we report a unique case of radiation-induced osteosarcomas arising on the skull and extending to the skin, with a short latent period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Case of postradiation osteosarcoma with a short latency period of 3 years.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12558870", "endSection": "title" } ] }, { "body": "What are manifestations of the Saint's Triad?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3614758", "http://www.ncbi.nlm.nih.gov/pubmed/1006494", "http://www.ncbi.nlm.nih.gov/pubmed/21590441", "http://www.ncbi.nlm.nih.gov/pubmed/19921348", "http://www.ncbi.nlm.nih.gov/pubmed/26366362", "http://www.ncbi.nlm.nih.gov/pubmed/26943439", "http://www.ncbi.nlm.nih.gov/pubmed/8927353", "http://www.ncbi.nlm.nih.gov/pubmed/18704619", "http://www.ncbi.nlm.nih.gov/pubmed/3827637" ], "ideal_answer": [ "Saint's Triad includes hiatus hernia, gallstones, and diverticulosis coli." ], "exact_answer": [ [ "hiatus hernia" ], [ "gallstones" ], [ "diverticulosis coli" ] ], "type": "list", "id": "5e2fa276fbd6abf43b000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Yamanaka et al. described two case studies involving coexistent cholelithiasis, hiatal hernia, and umbilical hernias, and discussed clinical similarities with the classical features of the Saint's triad. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26943439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Umbilical hernia with cholelithiasis and hiatal hernia: a clinical entity similar to Saint's triad.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26366362", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "We experienced two cases involving the simultaneous presence of cholelithiasis, hiatal hernia, and umbilical hernia. Both patients were female and overweight (body mass index of 25.0-29.9\u00a0kg/m(2)) and had a history of pregnancy and surgical treatment of cholelithiasis. Additionally, both patients had two of the three conditions of Saint's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26366362", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1218, "text": "In 1948, Saint's Triad, an aggregation of hiatus hernia (later, any primary hernia), gallstones, and diverticulosis coli, was introduced. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21590441", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 886, "text": "Remarkably, clinical studies of Saint's triad extending over the past 60 years have repeatedly demonstrated a highly significant relationship between colonic diverticula and abdominal herniae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19921348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: Sixty years ago, Saint's triad (hiatus hernia, diverticulosis of the colon, and gallbladder disease) was first described in three patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18704619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "In connection with two cases authors review our current body of knowledge on Saint's triad that means the concomitant occurrence of cholelithiasis, hiatus hernia and colonic diverticulosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8927353", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 463, "text": "The investigation revealed 7 cases of Saint's triad (1.02%) and 86 cases of bifocal associations; 59 cholelithiasis + diverticulosis, 17 cholelithiasis + Hiatus hernia; 10 diverticulosis + hernia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3614758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "The morphologic changes are described found in the gallbladder of a female patient, aged 40; she had xanthogranulomatous cholecystitis secondary to cholelithiasis combined with a hiatal hernia and multiple duodenal diverticulae (Saint's triad).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3827637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "A quarter of a century ago Professor C. F. M. Saint of the University of Cape Town noted the occasional association of diverticular disease, hiatus hernia, and gallstones in a patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1006494", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 767, "text": "Authors stress that in the event of simultaneous symptoms suggestive of atypic cholelithiasis , colonic diverticulosis and hiatus hernia one has to consider a potential Saint 's triad", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8927353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "In connection with two cases authors review our current body of knowledge on Saint 's triad that means the concomitant occurrence of cholelithiasis , hiatus hernia and colonic diverticulosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8927353", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1270, "text": "In 1948 , Saint 's Triad , an aggregation of hiatus hernia ( later , any primary hernia) , gallstones , and diverticulosis coli , was introduced", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21590441", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1589, "text": "CONCLUSIONS\nHerniosis, the systemic connective tissue disease known to cause diverticulosis and herniae, may be responsible for Saint's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18704619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND\nSixty years ago, Saint's triad (hiatus hernia, diverticulosis of the colon, and gallbladder disease) was first described in three patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18704619", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 464, "text": "The investigation revealed 7 cases of Saint's triad (1.02%) and 86 cases of bifocal associations; 59 cholelithiasis + diverticulosis, 17 cholelithiasis + Hiatus hernia; 10 diverticulosis + hernia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3614758", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 758, "text": "Authors stress that in the event of simultaneous symptoms suggestive of atypic cholelithiasis, colonic diverticulosis and hiatus hernia one has to consider a potential Saint's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8927353", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Erdafitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31088831", "http://www.ncbi.nlm.nih.gov/pubmed/31340094", "http://www.ncbi.nlm.nih.gov/pubmed/30021048", "http://www.ncbi.nlm.nih.gov/pubmed/31602692", "http://www.ncbi.nlm.nih.gov/pubmed/30065926", "http://www.ncbi.nlm.nih.gov/pubmed/31770593", "http://www.ncbi.nlm.nih.gov/pubmed/28341788", "http://www.ncbi.nlm.nih.gov/pubmed/31161538", "http://www.ncbi.nlm.nih.gov/pubmed/29950346", "http://www.ncbi.nlm.nih.gov/pubmed/31544541", "http://www.ncbi.nlm.nih.gov/pubmed/31673875", "http://www.ncbi.nlm.nih.gov/pubmed/28965185", "http://www.ncbi.nlm.nih.gov/pubmed/28416604" ], "ideal_answer": [ "Erdafitinib is an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor." ], "type": "summary", "id": "5e31af4bfbd6abf43b00004b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28965185", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Introduction This phase 1, open-label, multicenter, single-arm, dose-escalation study aimed to evaluate safety, pharmacokinetics (PK), and pharmacodynamics of erdafitinib (JNJ-42756493), an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, and to determine the recommended phase 2 dose in Japanese patients with advanced or refractory solid tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28965185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Findings from a phase II study indicate clinical efficacy with erdafitinib in patients with FGFR-altered inoperable or metastatic urothelial carcinoma. Robust responses were seen with this investigational pan-FGFR inhibitor, including in patients who did not respond to prior immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29950346", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 456, "text": "In a phase 1 clinical trial, erdafitinib, a pan FGFR inhibitor, was well tolerated with a manageable toxicity profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30021048", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 881, "text": "Co-cultured fibroblasts promoted SW620 and HCT116 CRC spheroid invasion, and this was prevented by the SRC and FGFR kinase inhibitors Dasatinib and Erdafitinib, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30065926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28341788", "endSection": "title" }, { "offsetInBeginSection": 339, "offsetInEndSection": 539, "text": "JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28341788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Oncogenic Characterization and Pharmacologic Sensitivity of Activating Fibroblast Growth Factor Receptor (FGFR) Genetic Alterations to the Selective FGFR Inhibitor Erdafitinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416604", "endSection": "title" }, { "offsetInBeginSection": 564, "offsetInEndSection": 766, "text": "Pathway inhibition in response to FGFR inhibitor treatment was assessed in cell lines (both in vitro and in vivo) and in samples from patients treated with the FGFR inhibitor JNJ-42756493 (erdafitinib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416604", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1292, "text": "Tumor cells expressing these FGFR activating mutants displayed sensitivity to the selective FGFR inhibitor erdafitinib and resulted in suppression of FGFR phosphorylation and downstream signal transduction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416604", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 411, "text": "Erdafitinib, a tyrosine kinase inhibitor of FGFR1-4, has shown antitumor activity in preclinical models and in a phase 1 study involving patients with __i_tag__ FGFR __end_i_tag__ alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31340094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Erdafitinib (Balversa\u2122, Janssen Pharmaceutical Companies) is a pan-fibroblast growth factor receptor (FGFR) inhibitor that was recently approved in the USA for the treatment of locally advanced or metastatic FGFR3 or FGFR2 urothelial carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31161538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31088831", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 542, "text": "JNJ-42756493 , erdafitinib , is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28341788", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 731, "text": "This review covers the preclinical and clinical evidence for erdafitinib , summarizes the results of other FGFR inhibitors tested in UC and explores future perspectives of FGFR inhibition in UC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31544541", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 979, "text": "Erdafitinib was the first orally effective FGFR antagonist approved by the FDA (2019) for the treatment of advanced cancer, that of the urinary bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31770593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Erdafitinib, a potent oral fibroblast growth factor receptor inhibitor, is a low extraction ratio drug highly bound to alpha-1-acid glycoprotein (AGP) with free fraction (fu ) varying across populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31602692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 386, "text": "Introduction This phase 1, open-label, multicenter, single-arm, dose-escalation study aimed to evaluate safety, pharmacokinetics (PK), and pharmacodynamics of erdafitinib (JNJ-42756493), an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, and to determine the recommended phase 2 dose in Japanese patients with advanced or refractory solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28965185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "BACKGROUND AND OBJECTIVES\nErdafitinib, an oral selective pan-fibroblast growth factor receptor (FGFR) kinase inhibitor, is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31673875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Erdafitinib, a potent oral fibroblast growth factor receptor inhibitor, is a low extraction ratio drug highly bound to alpha-1-acid glycoprotein (AGP) with free fraction (fu ) varying across populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31602692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 385, "text": "Introduction This phase 1, open-label, multicenter, single-arm, dose-escalation study aimed to evaluate safety, pharmacokinetics (PK), and pharmacodynamics of erdafitinib (JNJ-42756493), an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, and to determine the recommended phase 2 dose in Japanese patients with advanced or refractory solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28965185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Erdafitinib, an oral selective pan-fibroblast growth factor receptor (FGFR) kinase inhibitor, is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31673875", "endSection": "abstract" } ] }, { "body": "Are male or female persons more prone to autoimmunity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17108242", "http://www.ncbi.nlm.nih.gov/pubmed/25956531", "http://www.ncbi.nlm.nih.gov/pubmed/30394940", "http://www.ncbi.nlm.nih.gov/pubmed/18603021", "http://www.ncbi.nlm.nih.gov/pubmed/508371", "http://www.ncbi.nlm.nih.gov/pubmed/1958563", "http://www.ncbi.nlm.nih.gov/pubmed/22155196", "http://www.ncbi.nlm.nih.gov/pubmed/16549717" ], "ideal_answer": [ "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases.", "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. Most recently, sex chromosome abnormalities and skewed X chromosome inactivation have been suggested as novel players, particularly in later-onset diseases.", "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. Examples of this autoimmune dimorphism include (but are not limited to) lupus, rheumatoid arthritis and multiple sclerosis with the two former more prevalent in females than males and the latter more severe during pregnancy. Most recently, sex chromosome abnormalities and skewed X chromosome inactivation have been suggested as novel players, particularly in later-onset diseases.", "females", "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation." ], "exact_answer": [ "Female" ], "type": "factoid", "id": "5cebf83ea49efeb44c00000a", "snippets": [ { "offsetInBeginSection": 594, "offsetInEndSection": 683, "text": " Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/508371", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 1042, "text": "we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X-linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/508371", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 945, "text": "Examples of this autoimmune dimorphism include (but are not limited to) lupus, rheumatoid arthritis and multiple sclerosis with the two former more prevalent in females than males and the latter more severe during pregnancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1958563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17108242", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 635, "text": "Sex hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16549717", "endSection": "abstract" }, { "offsetInBeginSection": 1329, "offsetInEndSection": 1561, "text": "ex hormones affect the function of the mammalian immune system, and sex hormone expression is different in patients with systemic lupus erythematosus than in healthy subjects. Sex hormones play a role in the genesis of autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16549717", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 876, "text": "Most recently, sex chromosome abnormalities and skewed X chromosome inactivation have been suggested as novel players, particularly in later-onset diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18603021", "endSection": "abstract" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1679, "text": "As a result we may hypothesize that more than one mechanism may contribute to the female susceptibility to tolerance breakdown while the possibility that unknown factors may indeed protect men from AID should not be overlooked.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22155196", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 651, "text": " The gut microbiome, which impacts the innate and adaptive branches of immunity, not only influences the development of autoimmune disorders but may interact with sex-hormones to modulate disease progression and sex-bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25956531", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 545, "text": "Recent studies investigating the origins of sex bias in autoimmune disease have revealed an extensive and interconnected network of genetic, hormonal, microbial, and environmental influences. Investigation of sex hormones has moved beyond profiling the effects of hormones on activity and prevalence of immune cell types to defining the specific immunity-related genes driving these changes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394940", "endSection": "abstract" } ] }, { "body": "Which is the phenotype of the disease fibrodysplasia ossificans progressiva?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29033382", "http://www.ncbi.nlm.nih.gov/pubmed/26049728", "http://www.ncbi.nlm.nih.gov/pubmed/27881824" ], "ideal_answer": [ "Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints." ], "exact_answer": [ "3.\tFibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints." ], "type": "factoid", "id": "5e5b8b4e752ebcdc7a000001", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 142, "text": "Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder in which heterotopic bone forms in the soft tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29033382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Metaphyseal bony outgrowths are a well-recognized feature of fibrodysplasia ossificans progressiva (FOP) phenotype, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27881824", "endSection": "abstract" } ] }, { "body": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22120008", "http://www.ncbi.nlm.nih.gov/pubmed/29517398", "http://www.ncbi.nlm.nih.gov/pubmed/28525751" ], "ideal_answer": [ "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression.", "gene repression", "The nuclear lamina contributes to the regulation of gene expression and to chromatin organization. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes.", "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes.", "No, lamina-associated domains (LADs) are involved in transcriptional silencing and chromatin compaction.", "Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression.", "Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. The nuclear lamina contributes to the regulation of gene expression and to chromatin organization.", "Lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression", "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. The nuclear lamina contributes to the regulation of gene expression and to chromatin organization." ], "exact_answer": "no", "type": "yesno", "id": "5cf4dec0a49efeb44c00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120008", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120008", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 251, "text": "Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28525751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The nuclear lamina contributes to the regulation of gene expression and to chromatin organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29517398", "endSection": "abstract" } ] }, { "body": "Is Hemochromatosis type 4 is caused by a mutation in a recessive gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20039160", "http://www.ncbi.nlm.nih.gov/pubmed/24714983", "http://www.ncbi.nlm.nih.gov/pubmed/29154924", "http://www.ncbi.nlm.nih.gov/pubmed/30500107", "http://www.ncbi.nlm.nih.gov/pubmed/12547233" ], "ideal_answer": [ "No, Hemochromatosis type 4 is caused by an autosomal dominant gene", "type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations.", "Hemochromatosis type 4, also known as ferroportin disease, is an autosomal dominant genetic disorder caused by pathogenic mutations in the SLC40A1 gene, which encodes ferroportin 1 (FPN1)" ], "exact_answer": "no", "type": "yesno", "id": "5e31cc22fbd6abf43b000050", "snippets": [ { "offsetInBeginSection": 83, "offsetInEndSection": 245, "text": " severely affect iron homeostasis causing type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29154924", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 207, "text": "Hemochromatosis type 4, also known as ferroportin disease, is an autosomal dominant genetic disorder caused by pathogenic mutations in the SLC40A1 gene, which encodes ferroportin 1 (FPN1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30500107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Hemochromatosis type 4 is a rare form of primary iron overload transmitted as an autosomal dominant trait caused by mutations in the gene encoding the iron transport protein ferroportin 1 (SLC40A1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24714983", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1086, "text": "Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20039160", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1093, "text": "Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20039160", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1087, "text": "Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20039160", "endSection": "abstract" } ] }, { "body": "What is the purpose of the LINCS Project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24518066", "http://www.ncbi.nlm.nih.gov/pubmed/25036040", "http://www.ncbi.nlm.nih.gov/pubmed/28769090", "http://www.ncbi.nlm.nih.gov/pubmed/30255785", "http://www.ncbi.nlm.nih.gov/pubmed/27796074" ], "ideal_answer": [ "The Library of Integrated Network-Based Cellular Signatures (LINCS) project aims to create a network-based understanding of biology by cataloging changes in gene expression and signal transduction that occur when cells are exposed to a variety of perturbations.", "The functional annotation of the mammalian genome using sequencing (LINCS) project aims to systematically map all mammalian cell-type-specific transcriptomes with wide applications in biomedical research. TheLINCS annotation system, consisting of automated computational prediction, manual curation, and final expert curations, facilitated the comprehensive characterization of the human transcriptome, and could be applied to the transcriptomes of other species.", "The library of Integrated Cellular Signatures Project (LINCS) is an international effort for creating an annotated transcriptome and translating science into improved health care to benefit patients. TheLINCS aims to systematically map all human transcriptomes, chromosome by chromosome, in a gene-dependent manner through dedicated efforts from national and international teams.", "The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations." ], "type": "summary", "id": "5cf7835fa49efeb44c000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27796074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24518066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "The Library of Integrated Network-Based Cellular Signatures (LINCS) project aims to create a network-based understanding of biology by cataloging changes in gene expression and signal transduction that occur when cells are exposed to a variety of perturbations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25036040", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 593, "text": "Using transcriptome data from the L1000 database of the LINCS project, we developed a framework based on a deep-learning algorithm to predict potential drug target interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30255785", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 270, "text": "First, the LINCS project can provide rich transcriptome data that reflect the responses of cells upon exposure to various drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769090", "endSection": "abstract" } ] }, { "body": "Can Patient-derived organoids (PDOs) recapitulate patient responses in the clinic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "http://www.ncbi.nlm.nih.gov/pubmed/30629588" ], "ideal_answer": [ "Yes. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. In summary, PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.", "Yes. Patient-derived organoids (PDOs) can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs." ], "exact_answer": "yes", "type": "yesno", "id": "5e371a1db5b409ea53000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 959, "text": "Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 959, "text": "Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 650, "text": "Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 444, "text": "Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 308, "text": "Patient-derived xenografts (PDX) and patient-derived organoids (PDO) serve as promising tools to identify new drugs with therapeutic potential in PDAC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30629588", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 958, "text": "Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 968, "text": "Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 657, "text": "Molecular profiling of tumor organoids was matched to drug-screening results , suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 960, "text": "Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472484", "endSection": "abstract" } ] }, { "body": "What is Fuchs' Uveitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15947963", "http://www.ncbi.nlm.nih.gov/pubmed/28424877", "http://www.ncbi.nlm.nih.gov/pubmed/29944680" ], "ideal_answer": [ " Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation, which is associated with a gradual onset of decreased visual acuity.", " Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. ", "Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation, which is associated with a gradual onset of decreased visual acuity.", "Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation, which is associated with a gradual onset of decreased visual acuity. ", "Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation,", " Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous.", "Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous." ], "type": "summary", "id": "5e36dbdbb5b409ea5300000c", "snippets": [ { "offsetInBeginSection": 167, "offsetInEndSection": 273, "text": " Fuchs\u00b4 Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29944680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Fuchs uveitis (FU) is a\u00a0frequent, chronic course of intraocular inflammation, which is associated with a\u00a0gradual onset of decreased visual acuity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424877", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Fuchs uveitis (FU) is a\u00a0frequent, chronic course of intraocular inflammation, which is associated with a\u00a0gradual onset of decreased visual acuity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424877", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Fuchs uveitis syndrome (FUS) is typically a unilateral, chronic, low-grade inflammation of the anterior segment which manifests in young adulthood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15947963", "endSection": "abstract" } ] }, { "body": "Is overexpression of LY6K associated with better prognosis for non-small cell lung cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18089789" ], "ideal_answer": [ "No, LY6K overexpression is associated with poor prognosis for patients with NSCLC.", "No, overexpression of LY6K has been found to be associated with poor prognosis for non-small cell lung cancer patients." ], "exact_answer": "no", "type": "yesno", "id": "5e49c5336d0a277941000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 570, "text": "Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18089789", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 569, "text": "Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18089789", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 570, "text": "Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18089789", "endSection": "abstract" } ] }, { "body": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26814189", "http://www.ncbi.nlm.nih.gov/pubmed/30444046", "http://www.ncbi.nlm.nih.gov/pubmed/29198826", "http://www.ncbi.nlm.nih.gov/pubmed/17542650", "http://www.ncbi.nlm.nih.gov/pubmed/26738774" ], "ideal_answer": [ "The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Kruppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1.", "The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Here, using a reporter system, we show that TRIM28/ KRAB- ZNFs alter DNA methylation patterns in addition to H3 K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB- ZNFs ( ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes.", "The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Kruppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes", " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Kruppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes", "The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene", "The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1. Using several expression datasets, we identified KRAB- ZNFs ( ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene", "The proteins encoded by KRAB-ZNF genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation.", " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming.", "Yes, the members of the KRAB-ZNF gene family are involved in gene repression." ], "exact_answer": "yes", "type": "yesno", "id": "5d31daacb3a6380763000003", "snippets": [ { "offsetInBeginSection": 158, "offsetInEndSection": 348, "text": " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30444046", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 693, "text": "Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198826", "endSection": "abstract" }, { "offsetInBeginSection": 1511, "offsetInEndSection": 1644, "text": "Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26814189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Kr\u00fcppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26738774", "endSection": "abstract" }, { "offsetInBeginSection": 1962, "offsetInEndSection": 2150, "text": "Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17542650", "endSection": "abstract" }, { "offsetInBeginSection": 1776, "offsetInEndSection": 1959, "text": "Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17542650", "endSection": "abstract" } ] }, { "body": "What does the boxed warning of pimavanserin say?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28493654" ], "ideal_answer": [ "Pimavanserin bears a boxed warning about the risk of death associated with antipsychotic use in elderly patients with dementia." ], "exact_answer": [ "Risk of death associated with antipsychotic use in elderly patients with dementia" ], "type": "factoid", "id": "5e2dbd72fbd6abf43b000018", "snippets": [ { "offsetInBeginSection": 1819, "offsetInEndSection": 1953, "text": "Pimavanserin bears the same boxed warning about the risk of death associated with antipsychotic use in elderly patients with dementia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" } ] }, { "body": "List Cdk targets that are dephosphorylated during cytokinesis", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25371407" ], "ideal_answer": [ "Aip1, Ede1 and Inn1 are Cdk targets that are dephosphorylated during cytokinesis.", "The final event of the eukaryotic cell cycle is cytokinesis, when two new daughter cells are born. How the timing and execution of cytokinesis is controlled is poorly understood. A phosphoproteome analysis has identified Aip1, Ede1 and Inn1 as cytokinetic regulators. It seems that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes.", "Downregulation of cyclin-dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. Aip1, Ede1 and Inn1 are Cdk targets that are dephosphorylated at the time of cytoklesis." ], "exact_answer": [ [ "Aip1" ], [ "Ede1" ], [ "Inn1" ] ], "type": "list", "id": "5e36e093b5b409ea5300000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1093, "text": "The final event of the eukaryotic cell cycle is cytokinesis, when two new daughter cells are born. How the timing and execution of cytokinesis is controlled is poorly understood. Here, we show that downregulation of cyclin-dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. We use phosphoproteome analysis of mitotic exit to identify Cdk targets that are dephosphorylated at the time of cytokinesis. We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis. This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators. Our results suggest that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25371407", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 829, "text": "This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25371407", "endSection": "abstract" } ] }, { "body": "What is dystopia canthorum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21915450", "http://www.ncbi.nlm.nih.gov/pubmed/25224968", "http://www.ncbi.nlm.nih.gov/pubmed/14166458" ], "ideal_answer": [ "Dystopia canthorum is defined as a prominent broad nasal root with increased intercanthal distance." ], "exact_answer": [ "a prominent broad nasal root with increased intercanthal distance." ], "type": "factoid", "id": "5e361c8792b3349b55000001", "snippets": [ { "offsetInBeginSection": 200, "offsetInEndSection": 262, "text": "dystopia canthorum (lateral displacement of the inner canthi).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Waardenburg's syndrome consists of lateral displacement of the inner canthi of the eyes (dystopia canthorum), a broad nasal root and confluent eyebrows", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14166458", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 498, "text": "dystopia canthorum (lateral displacement of the inner canthi of the eyes),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25224968", "endSection": "abstract" } ] }, { "body": "Is the protein ABCG2 (ATP-Binding Cassette, subfamily G, member 2, transporter) excreting uric acid?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29264928", "http://www.ncbi.nlm.nih.gov/pubmed/28566086" ], "ideal_answer": [ "Yes,\r\nABCG2 plays a central role on extra-renal uric acid excretion" ], "exact_answer": "yes", "type": "yesno", "id": "5e5b5c6fb761aafe0900000a", "snippets": [ { "offsetInBeginSection": 255, "offsetInEndSection": 453, "text": "TP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is a well-studied urate transporter expressed on apical membranes in several tissues, including the intestine, liver, and kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29264928", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 329, "text": "the discovery that ABCG2 plays a central role on extra-renal uric acid excretion,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28566086", "endSection": "abstract" } ] }, { "body": "What is Heterochromia Iridis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27239603", "http://www.ncbi.nlm.nih.gov/pubmed/1480396", "http://www.ncbi.nlm.nih.gov/pubmed/28719537" ], "ideal_answer": [ "Heterochromia Iridis is a condition where the affected person has differences in the color of the iris.", "Heterochromia iridis is a rare autosomal recessive disorder of the iris, characterized by a heterochromatic pattern of inheritance, variable expressivity, and partial or total absence of iris and/or blonde hair.", "Heterochromia Iridis is a rare autosomal dominant disorder of melanocyte development characterized by heterochromatosis of the coronal, sagittal, and lambdoid sutures." ], "type": "summary", "id": "5e360b6a158f994d3a000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "The purpose of this study is to report a new and promising method for changing iris color in a sectorial heterochromia iridis patient. A 22-year-old man with a complaint of innate color disparity between his eyes presented to our clinic to seek medical advice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28719537", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 303, "text": "To present a case of iatrogenic Horner's syndrome seen together with the heterochromia in the post-thyroidectomy period.METHODS: A 23-year-old female patient was admitted to our clinic with complaints of low vision in the eye and difference in eye color that developed over the past two years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27239603", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 123, "text": "Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1480396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BACKGROUND\n\nHeterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1480396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "BACKGROUND Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1480396", "endSection": "abstract" } ] }, { "body": "How is transcriptional elongation affected by nucleosome positioning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7756302", "http://www.ncbi.nlm.nih.gov/pubmed/12596908", "http://www.ncbi.nlm.nih.gov/pubmed/7731795", "http://www.ncbi.nlm.nih.gov/pubmed/20829883", "http://www.ncbi.nlm.nih.gov/pubmed/22885008", "http://www.ncbi.nlm.nih.gov/pubmed/29212533", "http://www.ncbi.nlm.nih.gov/pubmed/1731087", "http://www.ncbi.nlm.nih.gov/pubmed/8327500" ], "ideal_answer": [ "In order to elongate their products, both DNA and RNA polymerases must be able to overcome the inhibition presented by chromatin. Nucleosome arrays inhibit both initiation and elongation of transcripts." ], "type": "summary", "id": "5d3883a0a1e1595105000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Nucleosome arrays inhibit both initiation and elongation of transcripts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1731087", "endSection": "title" }, { "offsetInBeginSection": 649, "offsetInEndSection": 845, "text": " Both transcript initiation and elongation were inhibited, the extent of the inhibition being directly proportional to the number of nucleosome cores reconstituted onto the pT207-18 DNA templates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1731087", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1306, "text": "neither partial nor complete dissociation of the histone octamer is essential for transcription elongation through arrays of nucleosome cores in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8327500", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 818, "text": "The high affinity of histones for single-stranded DNA observed in titration experiments performed using the purified (+) and (-) strands of the NX1 fragment suggests that nucleosome dissociation is not due to the formation of segments of single-stranded DNA by RNA polymerase in the elongation process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7756302", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1070, "text": "These effects are especially pronounced on chromatin templates, where both transcription initiation and elongation are virtually halted. The inhibition of transcription elongation appears to result from a dramatic increase in premature termination of transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7731795", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 732, "text": "By using this system, we show that BRG1, the enzymatic motor of the SWI-SNF chromatin-remodelling complex, is recruited to the positioned nucleosome in a transcription elongation-dependent manner and facilitates traversal of the nucleosome by RNAPII.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20829883", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 595, "text": "in order to elongate their products, both DNA and RNA polymerases must be able to overcome the inhibition presented by chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12596908", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1066, "text": " We suggest a three-step model in which nucleosome remodelers, general transcription factors, and the transcriptional elongation machinery are primarily involved in generating the nucleosome positioning pattern in\u00a0vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22885008", "endSection": "abstract" }, { "offsetInBeginSection": 2336, "offsetInEndSection": 2503, "text": "The independent effect of lack of TFIIS on nucleosome occupancy and fuzziness supports the existence of alternative chromatin dynamics during transcription elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212533", "endSection": "abstract" } ] }, { "body": "How many annotated conserved human lncRNAs come from ancestral protein-coding genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28854954" ], "ideal_answer": [ "~ 55", "~ 55 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs. Some lncRNAs inherited regulatory elements influencing transcription and translation from their protein-coding ancestors and those elements can influence the expression breadth and functionality of these lncRNAs." ], "exact_answer": [ "55" ], "type": "factoid", "id": "5e4940f46d0a277941000004", "snippets": [ { "offsetInBeginSection": 478, "offsetInEndSection": 1503, "text": "These lncRNAs have specific characteristics, such as broader expression domains, that set them apart from other lncRNAs. Fourteen lncRNAs have sequence similarity with the loci of the contemporary homologs of the lost protein-coding genes. We propose that selection acting on enhancer sequences is mostly responsible for retention of these regions. As an example of an RNA element from a protein-coding ancestor that was retained in the lncRNA, we describe in detail a short translated ORF in the JPX lncRNA that was derived from an upstream ORF in a protein-coding gene and retains some of its functionality.CONCLUSIONS: We estimate that\u2009~\u200955 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs. Some lncRNAs inherited regulatory elements influencing transcription and translation from their protein-coding ancestors and those elements can influence the expression breadth and functionality of these lncRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28854954", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1294, "text": "CONCLUSIONS\n\nWe estimate that\u2009~\u200955 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28854954", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1289, "text": "CONCLUSIONS We estimate that ~ 55 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28854954", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1294, "text": "CONCLUSIONS\nWe estimate that\u2009~\u200955 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28854954", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1290, "text": "CONCLUSIONS: We estimate that\u2009~\u200955 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28854954", "endSection": "abstract" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1258, "text": "We estimate that\u2009~\u200955 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28854954", "endSection": "abstract" } ] }, { "body": "Is modified vaccinia Ankara effective for smallpox?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17977963", "http://www.ncbi.nlm.nih.gov/pubmed/26143613", "http://www.ncbi.nlm.nih.gov/pubmed/23523410", "http://www.ncbi.nlm.nih.gov/pubmed/15227622", "http://www.ncbi.nlm.nih.gov/pubmed/16840346", "http://www.ncbi.nlm.nih.gov/pubmed/28374245", "http://www.ncbi.nlm.nih.gov/pubmed/18683106", "http://www.ncbi.nlm.nih.gov/pubmed/25879867", "http://www.ncbi.nlm.nih.gov/pubmed/27146001", "http://www.ncbi.nlm.nih.gov/pubmed/17604541", "http://www.ncbi.nlm.nih.gov/pubmed/28256358", "http://www.ncbi.nlm.nih.gov/pubmed/19093767", "http://www.ncbi.nlm.nih.gov/pubmed/27327616", "http://www.ncbi.nlm.nih.gov/pubmed/26380340", "http://www.ncbi.nlm.nih.gov/pubmed/29652929", "http://www.ncbi.nlm.nih.gov/pubmed/26949713", "http://www.ncbi.nlm.nih.gov/pubmed/23523407" ], "ideal_answer": [ "Yes, modified vaccinia Ankara is effective for smallpox." ], "exact_answer": "yes", "type": "yesno", "id": "5e30f23cfbd6abf43b000042", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29652929", "endSection": "abstract" }, { "offsetInBeginSection": 1394, "offsetInEndSection": 1549, "text": "The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99\u00b78% (PRNT) and 99\u00b77% (ELISA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29652929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "INTRODUCTION: To guide the use of modified vaccinia Ankara (MVA) vaccine in response to a release of smallpox virus, the immunogenicity and safety of shorter vaccination intervals, and administration by jet injector (JI), were compared to the standard schedule of administration on Days 1 and 29 by syringe and needle (S&N).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28256358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Erratum: Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26949713", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27146001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN\u00ae) in 56-80-Year-Old Subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27327616", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND: Modified Vaccinia Ankara MVA-BN\u00ae is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27327616", "endSection": "abstract" }, { "offsetInBeginSection": 2243, "offsetInEndSection": 2360, "text": "CONCLUSIONS: One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27327616", "endSection": "abstract" }, { "offsetInBeginSection": 2592, "offsetInEndSection": 2825, "text": "The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27327616", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 407, "text": "Modified Vaccinia Ankara (MVA) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25879867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "BACKGROUND: Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1\u00d710(8) TCID50 in a volume of 0.5mL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26143613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "IMVAMUNE, an attenuated modified vaccinia Ankara virus vaccine for smallpox infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18683106", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Bavarian Nordic is developing IMVAMUNE, which is based on a live attenuated modified vaccinia Ankara virus, for the potential prevention of smallpox infection, particularly in those patients contraindicated to traditional smallpox vaccines, such as the immunocompromised and those with eczema or dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18683106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19093767", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Modified vaccinia Ankara: potential as an alternative smallpox vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15227622", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Evaluation of modified vaccinia virus Ankara as an alternative vaccine against smallpox in chronically HIV type 1-infected individuals undergoing HAART.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17604541", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Modified vaccinia Ankara: potential as an alternative smallpox vaccine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15227622", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Modified vaccinia Ankara ( MVA ) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile ( SNS ) as a liquid formulation for subcutaneous ( SC ) administration at a dose of 1\u00d710 ( 8 ) TCID50 in a volume of 0.5mL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26143613", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1603, "text": "Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26380340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "Bavarian Nordic is developing IMVAMUNE , which is based on a live attenuated modified vaccinia Ankara virus , for the potential prevention of smallpox infection , particularly in those patients contraindicated to traditional smallpox vaccines , such as the immunocompromised and those with eczema or dermatitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18683106", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 558, "text": "One of the most advanced and most promising vectors is the attenuated , non-replicating poxvirus MVA ( modified vaccinia virus Ankara) , a safer derivative of the uniquely successful smallpox vaccine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Modified vaccinia virus Ankara ( MVA ) is a highly attenuated vaccinia virus that is under consideration as an alternative to the conventional smallpox vaccine Dryvax", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17977963", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 463, "text": "Modified Vaccinia virus Ankara ( MVA ) is an attenuated derivative , also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28374245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "While modified vaccinia virus Ankara ( MVA ) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases , its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16840346", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1584, "text": "Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26380340", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 465, "text": "Modified Vaccinia virus Ankara (MVA) is a replication-deficient and attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523410", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1583, "text": "\u2003Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26380340", "endSection": "abstract" } ] }, { "body": "Does nintedanib hold promise for lung disease associated with systemic sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23265249", "http://www.ncbi.nlm.nih.gov/pubmed/28664834", "http://www.ncbi.nlm.nih.gov/pubmed/31285305", "http://www.ncbi.nlm.nih.gov/pubmed/31747840", "http://www.ncbi.nlm.nih.gov/pubmed/29038968", "http://www.ncbi.nlm.nih.gov/pubmed/31423560", "http://www.ncbi.nlm.nih.gov/pubmed/31112379", "http://www.ncbi.nlm.nih.gov/pubmed/26973429", "http://www.ncbi.nlm.nih.gov/pubmed/31573469", "http://www.ncbi.nlm.nih.gov/pubmed/27560196", "http://www.ncbi.nlm.nih.gov/pubmed/28814429" ], "ideal_answer": [ "Yes, nintedanib holds promise for lung disease associated with systemic sclerosis. It is being tested in a clinical trial." ], "exact_answer": "yes", "type": "yesno", "id": "5e30f76afbd6abf43b000046", "snippets": [ { "offsetInBeginSection": 616, "offsetInEndSection": 1214, "text": "The patient developed progressive lung fibrosis under several immunosuppressants and was started on nintedanib, with clinical and functional stabilization. Nintedanib is a tyrosine-kinase inhibitor that blocks several profibrotic pathways, inhibiting proliferation and migration of fibroblasts and decreasing the synthesis of extracellular matrix proteins. It is approved for idiopathic lung fibrosis and has demonstrated good results in inhibiting migration and proliferation of systemic sclerosis dermal fibroblasts, constituting a promising agent for systemic sclerosis-associated lung fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29038968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28814429", "endSection": "abstract" }, { "offsetInBeginSection": 1618, "offsetInEndSection": 1974, "text": "CONCLUSION: Nintedanib targets core features of SSc in Fra2-transgenic mice and ameliorates histological features of pulmonary arterial hypertension, destructive microangiopathy and pulmonary and dermal fibrosis. These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28814429", "endSection": "abstract" }, { "offsetInBeginSection": 1076, "offsetInEndSection": 1453, "text": "In light of the ongoing advances in our understanding of the pathogenic mechanisms underlying interstitial lung disease in systemic sclerosis, this review also summarizes novel treatment approaches, presenting clinical and preclinical evidence for rituximab, tocilizumab, pirfenidone, and nintedanib, as well as hematopoietic stem cell transplantation and lung transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27560196", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 910, "text": "Pirfenidone and nintedanib are emerging agents that exert pleiotropic effects, reflective of the multiple mechanistic pathways of IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23265249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS\u2122).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28664834", "endSection": "title" }, { "offsetInBeginSection": 377, "offsetInEndSection": 544, "text": "The SENSCIS\u2122 trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28664834", "endSection": "abstract" }, { "offsetInBeginSection": 1652, "offsetInEndSection": 1751, "text": "CONCLUSIONS: This trial will assess the efficacy and safety of nintedanib in patients with SSc-ILD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28664834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31112379", "endSection": "title" }, { "offsetInBeginSection": 149, "offsetInEndSection": 307, "text": "Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31112379", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 493, "text": "METHODS\n\nWe conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31112379", "endSection": "abstract" }, { "offsetInBeginSection": 2154, "offsetInEndSection": 2400, "text": "CONCLUSIONS\n\nAmong patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31112379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Potential of Nintedanib in Treatment of Progressive Fibrosing Interstitial Lung Diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285305", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Anti-fibrotic nintedanib-a new opportunity for systemic sclerosis patients?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29038968", "endSection": "title" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1309, "text": "Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26973429", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1437, "text": "This suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285305", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1150, "text": "This suggests that nintedanib and pirfenidone , drugs known to slow disease progression in patients with idiopathic pulmonary fibrosis , may also slow the progression of ILD associated with systemic autoimmune diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423560", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1274, "text": "In the SENSCIS\u00ae trial , nintedanib reduced the rate of ILD progression in patients with systemic sclerosis-associated ILD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423560", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 307, "text": "Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31112379", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 543, "text": "The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31573469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "OBJECTIVES\nNintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31573469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Nintedanib: new indication for systemic sclerosis-associated interstitial lung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31747840", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Nintedanib (Ofev\u2122), an oral triple kinase inhibitor targeting pro-fibrotic pathways, has been used for treatment of idiopathic pulmonary fibrosis (IPF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31747840", "endSection": "abstract" }, { "offsetInBeginSection": 1831, "offsetInEndSection": 1974, "text": "These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28814429", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 446, "text": "Based on positive results from phase III, placebo-controlled, randomized comparative clinical trial conducted in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib received marketing approval in the United States and Japan for the treatment of SSc-ILD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31747840", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 738, "text": "Nintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31285305", "endSection": "abstract" } ] }, { "body": "What is the LINCS Program?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29122012", "http://www.ncbi.nlm.nih.gov/pubmed/29199020", "http://www.ncbi.nlm.nih.gov/pubmed/29140462", "http://www.ncbi.nlm.nih.gov/pubmed/24518066", "http://www.ncbi.nlm.nih.gov/pubmed/27187605", "http://www.ncbi.nlm.nih.gov/pubmed/29322930", "http://www.ncbi.nlm.nih.gov/pubmed/30157183" ], "ideal_answer": [ "The Library of Integrated Network-based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations.", "The National Institutes of Health library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource.", "To fill this gap, recently, the LINCS program generated almost 1.3 million profiles for over 40,000 drug and genetic perturbations for over 70 different human cell types, including meta information about the experimental conditions and cell lines The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level", "The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource. To fill this gap, recently, the LINCS program generated almost 1.3 million profiles for over 40,000 drug and genetic perturbations for over 70 different human cell types, including meta information about the experimental conditions and cell lines", "The library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data tools to improve our understanding of human diseases at the systems level.", "The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level. It has generated almost 1.3 million profiles for over 40,000 drug and genetic perturbations for over 70 different human cell types, including meta information about the experimental conditions and cell lines.", "The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level" ], "exact_answer": [ "NIH-funded program to generate a library of integrated, network-based, cellular signatures" ], "type": "factoid", "id": "5cea52c7a49efeb44c000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24518066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The NIH-funded LINCS program has been initiated to generate a library of integrated, network-based, cellular signatures (LINCS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27187605", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 253, "text": "Aiming to understand cellular responses to different perturbations, the NIH Common Fund Library of Integrated Network-based Cellular Signatures (LINCS) program involves many institutes and laboratories working on over a thousand cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322930", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1834, "text": "Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target characteristics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29122012", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 591, "text": "To fill this gap, recently, the LINCS program generated almost 1.3 million profiles for over 40,000 drug and genetic perturbations for over 70 different human cell types, including meta information about the experimental conditions and cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30157183", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 335, "text": "Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29140462", "endSection": "abstract" } ] }, { "body": "Is PF-05190457 an inverse agonist of the ghrelin receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27621150" ], "ideal_answer": [ "Yes, PF-05190457 is an inverse agonist of the ghrelin receptor." ], "exact_answer": "yes", "type": "yesno", "id": "5e49a1196d0a27794100000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621150", "endSection": "title" }, { "offsetInBeginSection": 5, "offsetInEndSection": 140, "text": "To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621150", "endSection": "abstract" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1571, "text": " PF-05190457 is a well-tolerated first-in-class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621150", "endSection": "abstract" } ] }, { "body": "Is Ubrogepant effective for migraine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "http://www.ncbi.nlm.nih.gov/pubmed/30681821", "http://www.ncbi.nlm.nih.gov/pubmed/31800988", "http://www.ncbi.nlm.nih.gov/pubmed/31341711", "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "http://www.ncbi.nlm.nih.gov/pubmed/30242830", "http://www.ncbi.nlm.nih.gov/pubmed/29556965", "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "http://www.ncbi.nlm.nih.gov/pubmed/28645128", "http://www.ncbi.nlm.nih.gov/pubmed/30403405", "http://www.ncbi.nlm.nih.gov/pubmed/29136283", "http://www.ncbi.nlm.nih.gov/pubmed/30475090", "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "http://www.ncbi.nlm.nih.gov/pubmed/31020659", "http://www.ncbi.nlm.nih.gov/pubmed/30995909" ], "ideal_answer": [ "Yes, Ubrogepant is effective for treatment of migraine." ], "exact_answer": "yes", "type": "yesno", "id": "5e30e9e3fbd6abf43b00003c", "snippets": [ { "offsetInBeginSection": 522, "offsetInEndSection": 778, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 765, "offsetInEndSection": 976, "text": "Despite the clear safety concerns, clinical trial data suggests that their intermittent use remains a viable and safe alternative, with 2 molecules remaining in clinical development (ubrogepant and rimegepant). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29556965", "endSection": "abstract" }, { "offsetInBeginSection": 1749, "offsetInEndSection": 1924, "text": "Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for acute treatment of migraine, but have not yet been submitted to the FDA for this indication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30242830", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1446, "text": "Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for the acute treatment of migraine, but have not yet been submitted to the FDA for this indication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30403405", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 536, "text": "Area covered: This review reports on compounds currently under development for the oral treatment of acute migraine attacks, focusing on Calcitonin-Gene-Related-Peptide receptor antagonists, specifically ubrogepant and rimegepant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30475090", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 878, "text": "Furthermore, new hope rises for the CGRP (calcitonin-gene related peptide)-antagonists, as the data for ubrogepant do not suggest hepatotoxicity but efficacy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28645128", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 388, "text": "We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "AIM: The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1084, "text": "Ubrogepant 100\u2009mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1553, "text": "CONCLUSION: This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 643, "text": "Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 777, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 452, "text": "Recent findings\n\nCalcitonin gene-related peptide (CGRP) receptor antagonists (gepants-rimegepant and ubrogepant) and serotonin 5-HT __sub__ 1F __end_sub__ receptor agonists (ditans-lasmiditan) have completed phase 3 clinical trials and will soon offer novel, effective, well-tolerated nonvasoconstrictor options to treat acute migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31341711", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 387, "text": "We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136283", "endSection": "abstract" }, { "offsetInBeginSection": 1954, "offsetInEndSection": 2226, "text": "Recently, orally administered next-generation small molecule CGRP-RAs have been shown to have safety and efficacy in acute treatment (ubrogepant and rimegepant) and prevention (atogepant) of migraine, giving additional CGRP-based therapeutic options for migraine patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31020659", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1088, "text": "Ubrogepant 100\u2009mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 555, "text": "Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30995909", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 552, "text": "Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30995909", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 728, "text": "Lasmiditan, ubrogepant, and rimegepant are currently emerging acute migraine therapies that may be added to the arsenal of current migraine management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30681821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Ubrogepant for the Treatment of Migraine .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31800988", "endSection": "title" }, { "offsetInBeginSection": 950, "offsetInEndSection": 1088, "text": "Ubrogepant 100\u2009mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1559, "text": "CONCLUSION\nThis trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive Phase III outcomes for acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1090, "text": "CONCLUSION: This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 1380, "offsetInEndSection": 1521, "text": "This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Ubrogepant for the Treatment of Migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31800988", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31800988", "endSection": "abstract" } ] }, { "body": "Is Selinexor effective for multiple myeloma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31433920", "http://www.ncbi.nlm.nih.gov/pubmed/29203585", "http://www.ncbi.nlm.nih.gov/pubmed/31793336", "http://www.ncbi.nlm.nih.gov/pubmed/30352784", "http://www.ncbi.nlm.nih.gov/pubmed/31332020", "http://www.ncbi.nlm.nih.gov/pubmed/31429063", "http://www.ncbi.nlm.nih.gov/pubmed/29381435", "http://www.ncbi.nlm.nih.gov/pubmed/28596644", "http://www.ncbi.nlm.nih.gov/pubmed/29610030", "http://www.ncbi.nlm.nih.gov/pubmed/29257139", "http://www.ncbi.nlm.nih.gov/pubmed/28668761", "http://www.ncbi.nlm.nih.gov/pubmed/29876006" ], "ideal_answer": [ "Yes, Selinexor is effective for multiple myeloma." ], "exact_answer": "yes", "type": "yesno", "id": "5e30f494fbd6abf43b000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29203585", "endSection": "title" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1611, "text": "Based on these findings, we conclude that selinexor in combination with dexamethasone is active in heavily pretreated MM and propose a RP2D of 45 mg/m2 (80 mg) plus 20 mg dexamethasone given twice weekly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29203585", "endSection": "abstract" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1555, "text": "Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29257139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29381435", "endSection": "title" }, { "offsetInBeginSection": 1603, "offsetInEndSection": 1768, "text": "Conclusion The combination of selinexor and dexamethasone has an ORR of 21% in patients with heavily pretreated, refractory myeloma with limited therapeutic options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29381435", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 1067, "text": "Selinexor (KPT-330) is the first-in-human SINE compound. Early phase clinical trials have established the safety profile of this agent and have shown promising efficacy in combination with low-dose dexamethasone and other anti-MM agents. The combination of selinexor and dexamethasone has demonstrated activity in \"penta-refractory\" MM, (ie, MM refractory to the 5 most active anti-MM agents currently used in treatment).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29610030", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 439, "text": "We found that DEX in combination with selinexor, an inhibitor of exportin-1 (XPO1) activity, synergistically inhibits the mTOR pathway and subsequently promotes cell death in MM cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29876006", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1260, "text": "The current findings are consistent with the beneficial therapeutic outcome in patients with MM when treated with the combination of selinexor and DEX. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29876006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30352784", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Selinexor is an oral inhibitor of the nuclear export protein exportin 1 (XPO1). Preclinical studies demonstrated synergistic antimyeloma activity between selinexor and proteasome inhibitors (PI) though suppression of NF\u03baB signaling and nuclear retention of tumor suppressor proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30352784", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 462, "text": "Targeting XPO1 with selinexor (the selective inhibitor of nuclear export; SINE compound KPT-330) demonstrates broad antitumor activity also in patient cells resistant to bortezomib; hence, it is a promising target in MM patients. Hypoxia is known to mediate tumor progression and drug resistance (including bortezomib resistance) in MM cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28668761", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1234, "text": "Selinexor, used as a single agent, delayed tumor initiation and tumor progression, prolonging mice survival. In bortezomib-resistant xenografts, selinexor overcame drug resistance, significantly decreasing tumor burden and extending mice survival when combined with bortezomib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28668761", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1114, "text": "The responses seen with venetoclax in RRMM with t(11;14)(high BCL-2, low BCL-XL and MCL-1) and selinexor in penta-refractory myeloma which fulfills the FDA category of unmet need, opens up newer options for these patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28596644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The FDA granted accelerated approval to selinexor plus low-dose dexamethasone for triple-class refractory multiple myeloma , despite an advisory panel 's concerns about the drug 's toxicity and the lack of randomized clinical data .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31332020", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 370, "text": "Selinexor ( in combination with dexamethasone ) received accelerated approval in the USA in July 2019 for the treatment of adult patients with relapsed or refractory multiple myeloma ( RRMM) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31429063", "endSection": "abstract" }, { "offsetInBeginSection": 1967, "offsetInEndSection": 2115, "text": "CONCLUSIONS\nSelinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31433920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Selinexor: A First-in-Class Nuclear Export Inhibitor for Management of Multiply Relapsed Multiple Myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31793336", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of selinexor for management of relapsed multiple myeloma (MM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31793336", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 358, "text": "Selinexor (in combination with dexamethasone) received accelerated approval in the USA in July 2019 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31429063", "endSection": "abstract" } ] }, { "body": "What is the protein product of the gene GBA2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29524657", "http://www.ncbi.nlm.nih.gov/pubmed/29234271", "http://www.ncbi.nlm.nih.gov/pubmed/30308956" ], "ideal_answer": [ "The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose." ], "exact_answer": [ "The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose." ], "type": "factoid", "id": "5e5bab131af46fc130000001", "snippets": [ { "offsetInBeginSection": 907, "offsetInEndSection": 934, "text": "b-glucosidase 2 gene (GBA2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The non-lysosomal glucosylceramidase GBA2 catalyzes the hydrolysis of glucosylceramide to glucose and ceramide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29234271", "endSection": "abstract" } ] }, { "body": "Are there lncRNAs that control the extent of neuronal outgrowth?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30401432" ], "ideal_answer": [ "Yes. there are lncRNAs which regulate the extent of neuronal outgrowth.", "Yes. LncRNAs are involved in a variety of biological processes, including the epigenetic control of gene expression, post-transcriptional regulation of mRNA, and neuronal outgrowth." ], "exact_answer": "yes", "type": "yesno", "id": "5e447f2448dab47f26000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Regulation of Neuroregeneration by Long Noncoding RNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30401432", "endSection": "title" }, { "offsetInBeginSection": 308, "offsetInEndSection": 774, "text": "Here, we profiled gene expression following sciatic nerve crush in mice and identified long noncoding RNAs (lncRNAs) that act in the regenerating neurons and which are typically not expressed in other contexts. We show that two of these lncRNAs regulate the extent of neuronal outgrowth. We then focus on one of these, Silc1, and show that it regulates neuroregeneration in cultured cells and in\u00a0vivo, through cis-acting activation of the transcription factor Sox11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30401432", "endSection": "abstract" } ] }, { "body": "Can the radiation of cellphones be dangerous?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19356911", "http://www.ncbi.nlm.nih.gov/pubmed/23302218" ], "ideal_answer": [ "two sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Dr. Lennart Hardell. The recent studies reach very different conclusions. With four exceptions the industry-funded Interphone studies found no increased risk of brain tumors from cellphone use, while the Swedish studies, independent of industry funding, reported numerous findings of significant increased brain tumor risk from cellphone and cordless phone use." ], "type": "summary", "id": "5e4705753f54159529000017", "snippets": [ { "offsetInBeginSection": 1632, "offsetInEndSection": 1952, "text": " While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23302218", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 612, "text": "two sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Dr. Lennart Hardell. The recent studies reach very different conclusions. With four exceptions the industry-funded Interphone studies found no increased risk of brain tumors from cellphone use, while the Swedish studies, independent of industry funding, reported numerous findings of significant increased brain tumor risk from cellphone and cordless phone use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19356911", "endSection": "abstract" } ] }, { "body": "Does metformin has as an antitumor effect?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29807100", "http://www.ncbi.nlm.nih.gov/pubmed/29422962", "http://www.ncbi.nlm.nih.gov/pubmed/29444159", "http://www.ncbi.nlm.nih.gov/pubmed/30053447" ], "ideal_answer": [ "Yes, \tThe anti-tumor effect of metformin is widely known." ], "exact_answer": "yes", "type": "yesno", "id": "5e4af1d86d0a277941000018", "snippets": [ { "offsetInBeginSection": 384, "offsetInEndSection": 435, "text": " an association between metformin and tumorigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29422962", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 132, "text": "Metformin, an antidiabetic drug, inhibits the endometrial cancer cell growth in vivo by improving the insulin resistance;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29444159", "endSection": "abstract" }, { "offsetInBeginSection": 1314, "offsetInEndSection": 1472, "text": "There is no evidence of antitumor effect of metformin. A possible decrease only for breast, liver and prostate cancer, is compatible with random fluctuations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29807100", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 347, "text": "The anti-tumor effect of metformin is widely known, however, there is only limited evidence regarding the anti-angiogenesis effect and chemosensitization of metformin and its underlying mechanisms in PDAC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053447", "endSection": "abstract" } ] }, { "body": "Can radiation induced meningiomas be treated with radiosurgery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15850899", "http://www.ncbi.nlm.nih.gov/pubmed/20418026", "http://www.ncbi.nlm.nih.gov/pubmed/18447746", "http://www.ncbi.nlm.nih.gov/pubmed/9032855", "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "http://www.ncbi.nlm.nih.gov/pubmed/28731398", "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "http://www.ncbi.nlm.nih.gov/pubmed/29104836" ], "ideal_answer": [ "Yes, radiation induced meningiomas be treated with radiosurgery. Radiosurgery provides satisfactory control of radiation induced meningiomas." ], "exact_answer": "yes", "type": "yesno", "id": "5e3234e0fbd6abf43b000054", "snippets": [ { "offsetInBeginSection": 257, "offsetInEndSection": 401, "text": "This is a case report of a patient treated with radiosurgery for radiation induced\u00a0meningiomas, 30 years after childhood whole brain radiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104836", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 984, "text": "This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Gamma knife stereotactic radiosurgery for radiation-induced meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "title" }, { "offsetInBeginSection": 760, "offsetInEndSection": 995, "text": "RESULTS: We present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution. With a median follow-up of 35 months, local control was 100%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 1303, "offsetInEndSection": 1414, "text": "CONCLUSIONS: Gamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Favorable outcomes of pediatric patients treated with radiotherapy to the central nervous system who develop radiation-induced meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20418026", "endSection": "title" }, { "offsetInBeginSection": 692, "offsetInEndSection": 838, "text": "All cases were managed with a single modality: resection alone (n = 7), fractionated radiotherapy (n = 2), and stereotactic radiosurgery (n = 1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20418026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Stereotactic radiosurgery for radiation-induced meningiomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "title" }, { "offsetInBeginSection": 386, "offsetInEndSection": 487, "text": "The patients met criteria for a radiation-induced meningioma and underwent gamma knife radiosurgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1563, "text": "CONCLUSION: SRS provides satisfactory control rates either after resection or as an alternative to resection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 400, "text": "This is a case report of a patient treated with radiosurgery for radiation induced\u00a0meningiomas, 30 years after childhood whole brain radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104836", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 983, "text": "This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104836", "endSection": "abstract" }, { "offsetInBeginSection": 1311, "offsetInEndSection": 1422, "text": "CONCLUSIONS\n\nGamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 939, "text": "RESULTS\n\nWe present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 1303, "offsetInEndSection": 1413, "text": "CONCLUSIONS Gamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 982, "text": "This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Stereotactic radiosurgery for radiation-induced meningiomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "title" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1463, "text": "Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15850899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Gamma Knife radiosurgery for meningiomas: four cases of radiation-induced edema.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9032855", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 402, "text": "This is a case report of a patient treated with radiosurgery for radiation induced\u00a0meningiomas , 30 years after childhood whole brain radiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104836", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 295, "text": "Stereotactic radiosurgery ( SRS ) has become an important primary or adjuvant management for patients with intracranial meningiomas , but the value of this approach for radiation-induced tumors is unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 991, "text": "This article reviews the unique characteristics and unusual response to the radiation induced meningiomas to radiosurgery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29104836", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 939, "text": "RESULTS\nWe present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 462, "text": "OBJECTIVES\nTo ascertain the safety and efficacy of Gamma Knife radiosurgery as a treatment for radiation-induced meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 334, "text": "As such, traditional radiotherapy is limited by lifetime tissue tolerances to radiation, leaving surgery and radiosurgery as attractive treatment options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 1311, "offsetInEndSection": 1422, "text": "CONCLUSIONS\nGamma Knife radiosurgery is both a safe and effective treatment for radiation-induced meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 303, "text": "Stereotactic radiosurgery (SRS) has become an important primary or adjuvant management for patients with intracranial meningiomas, but the value of this approach for radiation-induced tumors is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 488, "text": "The patients met criteria for a radiation-induced meningioma and underwent gamma knife radiosurgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 460, "text": "OBJECTIVES: To ascertain the safety and efficacy of Gamma Knife radiosurgery as a treatment for radiation-induced meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 933, "text": "RESULTS: We present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 650, "text": "METHODS: A retrospective chart review was conducted to identify patients who received Gamma Knife radiosurgery for a meningioma and met the criteria for this being a radiation-induced tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 894, "text": "We present our series of 12 patients with radiation-induced meningiomas treated with Gamma Knife stereotactic radiosurgery over a 12-year period at our institution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22922437", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 292, "text": "Stereotactic radiosurgery (SRS) has become an important primary or adjuvant management for patients with intracranial meningiomas, but the value of this approach for radiation-induced tumors is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19240608", "endSection": "abstract" } ] }, { "body": "What is known about ROS production in relation to UVR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29156345", "http://www.ncbi.nlm.nih.gov/pubmed/29532689", "http://www.ncbi.nlm.nih.gov/pubmed/28566124", "http://www.ncbi.nlm.nih.gov/pubmed/26996264", "http://www.ncbi.nlm.nih.gov/pubmed/30355644", "http://www.ncbi.nlm.nih.gov/pubmed/29740318" ], "ideal_answer": [ "Skin exposure to ultraviolet radiation (UVR) may induce the production of reactive oxygen species (ROS) which cause oxidative stress, DNA damage, and alteration of fibroblasts and collagen responsible for skin photoaging." ], "type": "summary", "id": "5e481b2cd14c9f295d00000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Human skin exposed to solar ultraviolet radiation (UVR) results in a dramatic increase in the production of reactive oxygen species (ROS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29740318", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 177, "text": "Studies have shown that skin exposure to ultraviolet radiation (UVR) results in the formation of reactive oxygen species (ROS), thus altering the cellular function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29532689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Skin exposure to ultraviolet radiation (UVR) may induce the production of reactive oxygen species (ROS) which cause oxidative stress, DNA damage, and alteration of fibroblasts and collagen responsible for skin photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30355644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Ultraviolet radiation (UVR) exposure causes various injurious effects to human skin by generating reactive oxygen species (ROS). Excessive ROS production can lead to oxidative stress which may damage cellular components like lipids and proteins and causing photoaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29156345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "Skin damage induced by UVR is an escalating problem in dermatology, and increasing incidence of skin cancer, especially for non-melanoma skin cancer, has been reported worldwide. UVR from sun exposure and the production of reactive oxygen species (ROS) is known to be a pivotal factor in the aetiology of skin cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28566124", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 207, "text": "Overexposure to ultraviolet (UV) derived from solar light causes skin damage by causing DNA lesions and the generation of reactive oxygen species (ROS) in keratinocytes and other epidermal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26996264", "endSection": "abstract" } ] }, { "body": "Which drugs used in the treatment of Systemic Lupus Erythematosus are targeting granulocytes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19341181", "http://www.ncbi.nlm.nih.gov/pubmed/9891923", "http://www.ncbi.nlm.nih.gov/pubmed/21993386", "http://www.ncbi.nlm.nih.gov/pubmed/623681", "http://www.ncbi.nlm.nih.gov/pubmed/27481040", "http://www.ncbi.nlm.nih.gov/pubmed/23821660" ], "ideal_answer": [ "Epratuzumab, a humanized monoclonal antibody against disialoganglioside, is the only officially approved treatment for the treatment of Systemic Lupus Erythematosus.Food and Drug Administration approval of SLE treatment with rituximab; however, more research is required before a large-scale application for clinical decision-making can be recommended.", "Systems responded to rituximab and cyclophosphamide.", "Cyclophosphamide and rituximab are used in the treatment of Systemic Lupus Erythematosus. GLPG-0634 and INCB18424 are other drugs that target and neutralize granulocytes." ], "exact_answer": [ [ "rituximab" ], [ "cyclophosphamide" ] ], "type": "list", "id": "5d2f3a5db3a6380763000001", "snippets": [ { "offsetInBeginSection": 587, "offsetInEndSection": 824, "text": "After treatment with any of the xenobiotic compounds, immunolabeling demonstrated the additional presence of granulocytes in foci, and, at electron microscope level neutrophils, eosinophils and their precursors were clearly recognizable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9891923", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1211, "text": "Cerebrospinal fluid (CSF) examination in patients with ATM in the course of SLE indicate usually pleocytosis with prevalence of granulocytes, increased protein levels, low glucose levels, significantly hindering differential diagnosis in the early stage of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19341181", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 913, "text": "Granulocytes isolated from 17 patients with systemic lupus erythematosus (SLE) had a significantly increased (P less than 0.001) mean initial rate of phagocytosis (0.91 min-u). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/623681", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 471, "text": "Both syndromes were refractory to conventional treatment but responded to rituximab and cyclophosphamide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993386", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 1006, "text": "Although some Fc-independent loss of CD22 is expected from internalization by epratuzumab, the concurrent and prominent reduction of CD19, CD21, and CD79b is Fc dependent and results from their transfer from epratuzumab-opsonized B cells to Fc\u03b3R-expressing monocytes, natural killer cells, and granulocytes via trogocytosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23821660", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 917, "text": " ANCA also occurs in 30%-40% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) and anti-GBM disease, but is uncommon in other forms of vasculitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481040", "endSection": "abstract" } ] }, { "body": "What is PWMScan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29514181" ], "ideal_answer": [ "Transcription factors regulate gene expression by binding to specific short DNA sequences of 5-20 bp to regulate the rate of transcription of genetic information from DNA to messenger RNA. PWMScan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database." ], "type": "summary", "id": "5e49c5ee6d0a277941000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "PWMScan: a fast tool for scanning entire genomes with a position-specific weight matrix.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 373, "text": "Transcription factors regulate gene expression by binding to specific short DNA sequences of 5-20 bp to regulate the rate of transcription of genetic information from DNA to messenger RNA. We present PWMScan, a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 373, "text": "We present PWMScan, a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 372, "text": "We present PWMScan, a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 367, "text": "We present PWMScan , a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 373, "text": "We present PWMScan, a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 364, "text": "We present PWMScan, a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "abstract" } ] }, { "body": "Is there a BRCA mutation analysis in the Greek population?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29310832" ], "ideal_answer": [ "Yes. Molecular analysis of the BRCA1 and BRCA2 genes in 898 Greek families was performed using Sanger sequencing or Next Generation Sequencing for the detection of small insertion/deletion frameshift, nonsynonymous, truncating and splice-site alterations and MLPA for the detection of large genomic rearrangements. In total, a pathogenic mutation was identified in 12.9% of 898 families analyzed. Of the 116 mutations identified in total 9% were novel and 14.7% were large genomic rearrangements." ], "exact_answer": "yes", "type": "yesno", "id": "5e3709a4b5b409ea53000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Comprehensive BRCA mutation analysis in the Greek population. Experience from a single clinical diagnostic center.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310832", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1246, "text": "Germline mutations in the BRCA1 and BRCA2 genes are associated with hereditary predisposition to breast and ovarian cancer. Sensitive and accurate detection of BRCA1 and BRCA2 mutations is crucial for personalized clinical management of individuals affected by breast or ovarian cancer, and for the identification of at-risk healthy relatives. We performed molecular analysis of the BRCA1 and BRCA2 genes in 898 Greek families, using Sanger sequencing or Next Generation Sequencing for the detection of small insertion/deletion frameshift, nonsynonymous, truncating and splice-site alterations and MLPA for the detection of large genomic rearrangements. In total, a pathogenic mutation was identified in 12.9% of 898 families analyzed. Of the 116 mutations identified in total 9% were novel and 14.7% were large genomic rearrangements. Our results indicate that different types of mutational events in the BRCA1 and BRCA2 genes are responsible for the hereditary component of breast/ovarian cancer in the Greek population. Therefore the methodology used in the analysis of Greek patients must be able to detect both point and small frameshift mutations in addition to large genomic rearrangements across the entire coding region of the two genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310832", "endSection": "abstract" } ] }, { "body": "What is the basis of the DamID experimental protocol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16972870", "http://www.ncbi.nlm.nih.gov/pubmed/26383089", "http://www.ncbi.nlm.nih.gov/pubmed/16938559", "http://www.ncbi.nlm.nih.gov/pubmed/16503134", "http://www.ncbi.nlm.nih.gov/pubmed/28189763", "http://www.ncbi.nlm.nih.gov/pubmed/29738692" ], "ideal_answer": [ " Dam Identification (DamID) system induced by Cre recombinase using Lamin B1 and mouse embryonic fibroblasts. This inducible system will help to generate genome-wide profiles of chromatin proteins in given cell types and tissues with no need to dissect tissues from organs or separate cells from tissues, which is achieved by using specific regulatory DNA elements and due to the high sensitivity of the method. DNA adenine methyltransferase identification (DamID) has emerged as one of the most comprehensive and versatile methods available for profiling protein-DNA interactions on a genomic scale. Recently, a novel methylation-based tagging technique, termed DamID (DNA adenine methyltransferase identification), has emerged as a powerful tool to decipher transcriptional networks, to study chromatin-associated proteins, and to monitor higher-order chromatin organization on a genome-wide scale. We show here that the in vivo methylation-based tagging technique DamID (DNA adenine methyltransferase identification) can be used for studies of DNA-protein interactions or chromatin profiling in plants DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible. ", "Recently, a novel methylation-based tagging technique, termed DamID (DNA adenine methyltransferase identification), has emerged as a powerful tool to decipher transcriptional networks, to study chromatin-associated proteins, and to monitor higher-order chromatin organization on a genome-wide scale. We show here that the in vivo methylation-based tagging technique DamID (DNA adenine methyltransferase identification) can be used for studies of DNA-protein interactions or chromatin profiling in plants Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible.", " Dam Identification (DamID) system induced by Cre recombinase using Lamin B1 and mouse embryonic fibroblasts. It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible.", "DNA adenine methyltransferase identification (DamID) has emerged as one of the most comprehensive and versatile methods available for profiling protein-DNA interactions on a genomic scale. It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites.", "This inducible system will help to generate genome-wide profiles of chromatin proteins in given cell types and tissues with no need to dissect tissues from organs or separate cells from tissues, which is achieved by using specific regulatory DNA elements and due to the high sensitivity of the method. DNA adenine methyltransferase identification (DamID) has emerged as one of the most comprehensive and versatile methods available for profiling protein-DNA interactions on a genomic scale. DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible.", "DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible." ], "type": "summary", "id": "5cf4eb6aa49efeb44c00000e", "snippets": [ { "offsetInBeginSection": 516, "offsetInEndSection": 927, "text": " Dam Identification (DamID) system induced by Cre recombinase using Lamin B1 and mouse embryonic fibroblasts. This inducible system will help to generate genome-wide profiles of chromatin proteins in given cell types and tissues with no need to dissect tissues from organs or separate cells from tissues, which is achieved by using specific regulatory DNA elements and due to the high sensitivity of the method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29738692", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 874, "text": "DNA adenine methyltransferase identification (DamID) has emerged as one of the most comprehensive and versatile methods available for profiling protein-DNA interactions on a genomic scale. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26383089", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 716, "text": "Recently, a novel methylation-based tagging technique, termed DamID (DNA adenine methyltransferase identification), has emerged as a powerful tool to decipher transcriptional networks, to study chromatin-associated proteins, and to monitor higher-order chromatin organization on a genome-wide scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16503134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "We show here that the in vivo methylation-based tagging technique DamID (DNA adenine methyltransferase identification) can be used for studies of DNA-protein interactions or chromatin profiling in plants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16972870", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 230, "text": "DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16938559", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 627, "text": " It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16938559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28189763", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 781, "text": " Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28189763", "endSection": "abstract" } ] }, { "body": "What is the function of the Spt6 gene in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25918242", "http://www.ncbi.nlm.nih.gov/pubmed/1330823", "http://www.ncbi.nlm.nih.gov/pubmed/29905868", "http://www.ncbi.nlm.nih.gov/pubmed/8844144", "http://www.ncbi.nlm.nih.gov/pubmed/21098123", "http://www.ncbi.nlm.nih.gov/pubmed/16455495", "http://www.ncbi.nlm.nih.gov/pubmed/9450930", "http://www.ncbi.nlm.nih.gov/pubmed/21057455", "http://www.ncbi.nlm.nih.gov/pubmed/24100010" ], "ideal_answer": [ "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Binding of elongation factor Spt6 to Iws1 provides an effective means for coupling eukaryotic mRNA synthesis, chromatin remodelling and mRNA export. Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I. Spt6 (suppressor of Ty6) has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression.", "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. Spt6 is a highly conserved factor required for normal transcription and chromatin structure.", "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression.", "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Binding of elongation factor Spt6 to Iws1 provides an effective means for coupling eukaryotic mRNA synthesis, chromatin remodelling and mRNA export. Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I. Spt6 (suppressor of Ty6) has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression. Previous characterization of the Saccharomyces cerevisiae Spt4, Spt5, and Spt6 proteins suggested that these proteins act as transcription factors that modify chromatin structure. The SPT4, SPT5, and SPT6 gene products define a class of transcriptional repressors in Saccharomyces cerevisiae that are thought to function through their effects on chromatin assembly or stability. The SPT4, SPT5 and SPT6 genes of Saccharomyces cerevisiae were identified originally by mutations that suppress delta insertion mutations at HIS4 and LYS2. Taken together, these genetic and biochemical results indicate that SPT4, SPT5 and SPT6 function together in a transcriptional process that is essential for viability in yeast. Next, we showed that CK2 interacts with the major histone chaperone Spt6, and phosphorylates it in vivo and in vitro. CK2 phosphorylation of Spt6 is required for its cellular levels ", "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. A transcriptional elongation factor, Spt6 is essential for rRNA Synthesis by RNA Polymerase I. Spt6 is the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression.", "These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression.", "These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression." ], "type": "summary", "id": "5cf619a8a49efeb44c000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24100010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Spt6 is a highly conserved factor required for normal transcription and chromatin structure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Binding of elongation factor Spt6 to Iws1 provides an effective means for coupling eukaryotic mRNA synthesis, chromatin remodelling and mRNA export. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21057455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25918242", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Spt6 (suppressor of Ty6) has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25918242", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 297, "text": "Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25918242", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 642, "text": "We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16455495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Previous characterization of the Saccharomyces cerevisiae Spt4, Spt5, and Spt6 proteins suggested that these proteins act as transcription factors that modify chromatin structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9450930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The SPT4, SPT5, and SPT6 gene products define a class of transcriptional repressors in Saccharomyces cerevisiae that are thought to function through their effects on chromatin assembly or stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8844144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The SPT4, SPT5 and SPT6 genes of Saccharomyces cerevisiae were identified originally by mutations that suppress delta insertion mutations at HIS4 and LYS2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1330823", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1052, "text": "Taken together, these genetic and biochemical results indicate that SPT4, SPT5 and SPT6 function together in a transcriptional process that is essential for viability in yeast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1330823", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 893, "text": "Next, we showed that CK2 interacts with the major histone chaperone Spt6, and phosphorylates it in vivo and in vitro. CK2 phosphorylation of Spt6 is required for its cellular levels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29905868", "endSection": "abstract" } ] }, { "body": "What has pimavanserin been approved for by the FDA (2018)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28493654" ], "ideal_answer": [ "Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis." ], "exact_answer": [ "hallucinations and delusions associated with Parkinson's disease psychosis" ], "type": "factoid", "id": "5e2dbc55fbd6abf43b000016", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 251, "text": "To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1505, "text": "Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28493654", "endSection": "abstract" } ] }, { "body": "List the members of a network of noncoding regulatory RNAs that play a role in the mammalian brain", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29887379" ], "ideal_answer": [ "In mice, the long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7-targeted mRNAs and enables accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as in neurons, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network." ], "exact_answer": [ [ "long ncRNA Cyrano" ], [ "miR-7 miRNA" ], [ "Cdr1as circular RNA" ], [ "miR-671 miRNA" ] ], "type": "list", "id": "5e49c88c6d0a277941000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1010, "text": "Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs-a long ncRNA, a circular RNA, and two microRNAs-using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7-targeted mRNAs and enables accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as in neurons, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29887379", "endSection": "abstract" } ] }, { "body": "Has ProSavin undergone phase IV clinical trials by 2018?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24412048" ], "ideal_answer": [ "No, ProSavin has undergone a dose escalation, open-label, phase 1/2 trial." ], "exact_answer": "no", "type": "yesno", "id": "5e2dbf48fbd6abf43b00001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24412048", "endSection": "title" }, { "offsetInBeginSection": 555, "offsetInEndSection": 783, "text": "We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24412048", "endSection": "abstract" } ] }, { "body": "List approved radioprotective compounds", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25525844" ], "ideal_answer": [ "Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy." ], "exact_answer": [ [ "amifostine" ], [ "palifermin" ] ], "type": "list", "id": "5e5cbf4e1af46fc130000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525844", "endSection": "abstract" } ] }, { "body": "Does deletion of cohesin change gene expression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25677180" ], "ideal_answer": [ " The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements.", "Yes. Deletion of cohesin inhibits gene expression at multiple points within the genome and in different genomic regions.", "The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements.", "We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter \"connections\" and \"insulation.\". The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements.", "Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter \"connections\" and \"insulation.\"", "Yes. Numerous studies have demonstrated that deletion of cohesin reduces gene expression at multiple points within the genome." ], "exact_answer": "yes", "type": "yesno", "id": "5d35b9ecb3a6380763000004", "snippets": [ { "offsetInBeginSection": 932, "offsetInEndSection": 1115, "text": " The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25677180", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1301, "text": "Interestingly, \u223c 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25677180", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1494, "text": "We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter \"connections\" and \"insulation.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25677180", "endSection": "abstract" } ] }, { "body": "Do MAIT cells have a role in multiple myeloma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30153633", "http://www.ncbi.nlm.nih.gov/pubmed/29515123" ], "ideal_answer": [ "Yes, MAIT cells may represent new immunotherapeutic targets for treatment of Multiple Myeloma and other malignancies", "Yes, MAIT cells have a role in multiple myeloma.", "Yes. Mucosal-associated invariant T cells (MAIT cells) play a key role in the pathogenesis of multiple myeloma." ], "exact_answer": "yes", "type": "yesno", "id": "5e2e1d6afbd6abf43b000026", "snippets": [ { "offsetInBeginSection": 1148, "offsetInEndSection": 1358, "text": "hus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 497, "text": "Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 822, "text": "Newly diagnosed MM patient MAIT cells had reduced IFN\u03b3 production and CD27 expression, suggesting an exhausted phenotype, although IFN\u03b3-producing capacity is restored in relapsed/refractory patient samples. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1418, "text": "We describe recent observations with regard to functional exhaustion of iNKT and MAIT cells in MM pathology and discuss the potential application of checkpoint inhibition as an attractive target for prolonged activation of these immunomodulatory T cells in the treatment of MM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30153633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123", "endSection": "title" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1358, "text": "Thus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515123", "endSection": "abstract" } ] }, { "body": "What is ProSavin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24412048", "http://www.ncbi.nlm.nih.gov/pubmed/30156440" ], "ideal_answer": [ "ProSavin, a lentiviral vector based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease. It has been shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. Moderate improvements in motor behavior over baseline continued to be reported in the majority of patients who could still be evaluated up to 5 years of follow-up." ], "type": "summary", "id": "5e2dbe17fbd6abf43b000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156440", "endSection": "title" }, { "offsetInBeginSection": 219, "offsetInEndSection": 466, "text": "ProSavin, a lentiviral vector based gene therapy that delivers local and continuous dopamine, was previously shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24412048", "endSection": "title" }, { "offsetInBeginSection": 293, "offsetInEndSection": 546, "text": "We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24412048", "endSection": "abstract" }, { "offsetInBeginSection": 2229, "offsetInEndSection": 2373, "text": "ProSavin was safe and well tolerated in patients with advanced Parkinson's disease. Improvement in motor behaviour was observed in all patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24412048", "endSection": "abstract" } ] }, { "body": "Are stretch enhancers transcribed more than super-enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30169995" ], "ideal_answer": [ "No. Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers.", "No. Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers. Importantly, most of the stretch enhancers that are distinct from super-enhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers." ], "exact_answer": "no", "type": "yesno", "id": "5e3e843748dab47f26000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "title" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1854, "text": "We found that stretch enhancers are more abundant, more distal to transcription start sites, cover twice as much the genome, and are significantly less conserved than super-enhancers. In contrast, super-enhancers are significantly more enriched for active chromatin marks and cohesin complex, and more transcriptionally active than stretch enhancers. Importantly, a vast majority of super-enhancers (85%) overlap with only a small subset of stretch enhancers (13%), which are enriched for cell type-specific biological functions, and control cell identity genes. These results suggest that super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers, and importantly, most of the stretch enhancers that are distinct from super-enhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1854, "text": "These results suggest that super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers, and importantly, most of the stretch enhancers that are distinct from super-enhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "abstract" } ] }, { "body": "What is Q-SYMBIO?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25282031" ], "ideal_answer": [ "Q-SYMBIO is a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality] that assessed coenzyme Q10 as adjunctive treatment of chronic heart failure. METHOD: Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis. CONCLUSION: Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events." ], "type": "summary", "id": "5e2dc047fbd6abf43b00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25282031", "endSection": "title" }, { "offsetInBeginSection": 425, "offsetInEndSection": 932, "text": "Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25282031", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 2024, "text": "Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25282031", "endSection": "abstract" } ] }, { "body": "What is the function of the NIPBL factor in genome conformation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18854353", "http://www.ncbi.nlm.nih.gov/pubmed/23760082", "http://www.ncbi.nlm.nih.gov/pubmed/28855971", "http://www.ncbi.nlm.nih.gov/pubmed/28914604", "http://www.ncbi.nlm.nih.gov/pubmed/30096364", "http://www.ncbi.nlm.nih.gov/pubmed/24550742", "http://www.ncbi.nlm.nih.gov/pubmed/25255084", "http://www.ncbi.nlm.nih.gov/pubmed/19468298" ], "ideal_answer": [ "The NIPBL protein stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes.. NIPBL recruits histone deacetylases to mediate local chromatin modifications.", "NIPBL loads cohesin onto chromatin. The NIPBL protein is required for the loading of cohesin onto chromatin. A cohesin-loading factor (NIPBL) is one of important regulatory factors in the maintenance of 3D genome organization and function, by interacting with a large number of factors, e.g. cohesion, CCCTC-binding factor (CTCF) or cohesin complex component. The mechanism of this gene regulation remains unclear, but NIPBL and cohesin have been reported to affect long-range chromosomal interactions, both independently and through interactions with CTCF.", "The Cohesin loading factor NIPBL recruits histone deacetylases to mediate local chromatin modifications." ], "type": "summary", "id": "5cebe907a49efeb44c000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The Cohesin loading factor NIPBL recruits histone deacetylases to mediate local chromatin modifications.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18854353", "endSection": "title" }, { "offsetInBeginSection": 78, "offsetInEndSection": 218, "text": "About half of the patients with CdLS carry mutations in the NIPBL gene encoding the NIPBL protein, a subunit of the Cohesin loading complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18854353", "endSection": "abstract" }, { "offsetInBeginSection": 1072, "offsetInEndSection": 1244, "text": " Our data are the first to indicate a molecular and functional connection of NIPBL with chromatin-remodeling processes via the direct interaction with histone deacetylases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18854353", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Cohesin regulates sister chromatid cohesion during the mitotic cell cycle with Nipped-B-Like (NIPBL) facilitating its loading and unloading", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19468298", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 475, "text": "Heterozygous mutations in the cohesin regulator NIPBL or cohesin structural components SMC1A and SMC3 result in the multisystem developmental disorder Cornelia de Lange Syndrome (CdLS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19468298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Cornelia de Lange syndrome (CdLS) is a developmental disorder caused by mutations in NIPBL, a protein which has functionally been associated with the cohesin complex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23760082", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 613, "text": "The mechanism of this gene regulation remains unclear, but NIPBL and cohesin have been reported to affect long-range chromosomal interactions, both independently and through interactions with CTCF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23760082", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 736, "text": "We used fluorescence in situ hybridization to investigate whether the disruption of NIPBL affects chromosome architecture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23760082", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1041, "text": "Cells carrying mutations predicted to have a more severe effect on NIPBL function show more extensive chromatin decompaction than those carrying milder mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23760082", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 240, "text": "The NIPBL protein is required for the loading of cohesin onto chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24550742", "endSection": "abstract" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1331, "text": " In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25255084", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 355, "text": " Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28914604", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 256, "text": "NIPBL loads cohesin onto chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28855971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "A cohesin-loading factor (NIPBL) is one of important regulatory factors in the maintenance of 3D genome organization and function, by interacting with a large number of factors, e.g. cohesion, CCCTC-binding factor (CTCF) or cohesin complex component. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30096364", "endSection": "abstract" } ] }, { "body": "Is mesothelioma caused by asbestos exposure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26024342", "http://www.ncbi.nlm.nih.gov/pubmed/23463177", "http://www.ncbi.nlm.nih.gov/pubmed/30479770", "http://www.ncbi.nlm.nih.gov/pubmed/27705549", "http://www.ncbi.nlm.nih.gov/pubmed/26418833", "http://www.ncbi.nlm.nih.gov/pubmed/30618090", "http://www.ncbi.nlm.nih.gov/pubmed/26161391", "http://www.ncbi.nlm.nih.gov/pubmed/28685333", "http://www.ncbi.nlm.nih.gov/pubmed/28910456", "http://www.ncbi.nlm.nih.gov/pubmed/23714495", "http://www.ncbi.nlm.nih.gov/pubmed/27462362", "http://www.ncbi.nlm.nih.gov/pubmed/8394641" ], "ideal_answer": [ "Yes, mesothelioma is caused by asbestos exposure.", "Yes, mesothelioma is a hard to treat malignant neoplasia caused by asbestos exposure.", "Yes, mesothelioma is a type of malignant mesothelial cancer caused by asbestos exposure.", "Yes, mesothelioma is caused by exposure to asbestos.", "Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure." ], "exact_answer": "yes", "type": "yesno", "id": "5e31c4adfbd6abf43b00004d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Malignant mesothelioma is a rare and aggressive pleural or peritoneal tumour almost always caused by exposure to asbestos fibres", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479770", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 211, "text": "Exposure to asbestos can cause malignant mesothelioma 30-40\u2009years after exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479770", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 175, "text": "Malignant peritoneal mesothelioma is a rare, aggressive tumor arising from the peritoneal lining, induced by asbestos, therapeutic radiation, or germline mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28910456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "According to global estimates, at least 107,000 people die each year from asbestos-related lung cancer, mesothelioma, and asbestosis resulting from occupational exposure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28685333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26161391", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 376, "text": "Malignant mesothelioma and lung cancer are caused by all major types of asbestos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26024342", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 211, "text": "Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "BACKGROUND Malignant mesothelioma caused by asbestos exposure has a long latency period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27462362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23463177", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 485, "text": "Most MPeM is caused by asbestos exposure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23714495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Occupational exposure to asbestos occurs in many workplaces and is well known to cause asbestosis , lung cancer , and mesothelioma . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26418833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Malignant mesothelioma is a rare and aggressive pleural or peritoneal tumour almost always caused by exposure to asbestos fibres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479770", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 212, "text": "Exposure to asbestos can cause malignant mesothelioma 30-40\u2009years after exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30479770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Malignant pleural mesothelioma caused by environmental exposure to asbestos or erionite in rural Turkey: CT findings in 84 patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8394641", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "OBJECTIVE\nMalignant pleural mesothelioma in rural Turkey frequently results from environmental exposure to tremolite asbestos or fibrous zeolite (erionite).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8394641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Mesothelioma, a rare tumor, is highly correlated with asbestos exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27705549", "endSection": "abstract" } ] }, { "body": "Which diagnostic test is approved for coronavirus infection screening?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14707219", "http://www.ncbi.nlm.nih.gov/pubmed/28191331", "http://www.ncbi.nlm.nih.gov/pubmed/24153118", "http://www.ncbi.nlm.nih.gov/pubmed/14522060" ], "ideal_answer": [ "Real-time reverse transcription-PCR (rRT-PCR) is mostly used as the lab test for screening coronaviral infection." ], "exact_answer": [ "real-time reverse transcription-PCR" ], "type": "factoid", "id": "5e5b8170b761aafe09000010", "snippets": [ { "offsetInBeginSection": 447, "offsetInEndSection": 845, "text": ": In this study, we present two real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for in-house rapid and sensitive diagnostic testing of MERS-CoV, detecting the regions upstream of the envelope gene (upE) and open reading frame (ORF) 1b, respectively, for initial screening and final confirmation of MERS-CoV infection, as recommended by the world health organization (WHO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28191331", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 473, "text": " In response, we developed two real-time reverse transcription-PCR (rRT-PCR) assays targeting the MERS-CoV nucleocapsid (N) gene and evaluated these assays as a panel with a previously published assay targeting the region upstream of the MERS-CoV envelope gene (upE) for the detection and confirmation of MERS-CoV infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153118", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1100, "text": "SARS-CoV was detected by means of reverse-transcriptase polymerase chain reaction (RT-PCR) in at least one specimen in 59 (54.1%) of 109 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14707219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Early diagnosis of SARS coronavirus infection by real time RT-PCR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14522060", "endSection": "title" } ] }, { "body": "What is Xanamem?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28012176" ], "ideal_answer": [ "UE2343 was identified as a potent, orally bioavailable, brain-penetrant 11b-HSD1 inhibitor and selected for clinical studies. Reducing glucocorticoid exposure in the brain via intracellular inhibition of the cortisol-regenerating enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) has emerged as a therapeutic strategy to treat cognitive impairment in early Alzheimer's disease (AD). UE2343 is safe, well tolerated and reaches the brain at concentrations predicted to inhibit 11b-HSD1. UE2343 is therefore a suitable candidate to test the hypothesis that 11b-HSD1 inhibition in brain improves memory in patients with AD." ], "type": "summary", "id": "5e2dfb52fbd6abf43b00001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Selection and early clinical evaluation of the brain-penetrant 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1) inhibitor UE2343 (Xanamem\u2122).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28012176", "endSection": "title" }, { "offsetInBeginSection": 824, "offsetInEndSection": 950, "text": "UE2343 was identified as a potent, orally bioavailable, brain-penetrant 11\u03b2-HSD1 inhibitor and selected for clinical studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28012176", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 289, "text": "Reducing glucocorticoid exposure in the brain via intracellular inhibition of the cortisol-regenerating enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1) has emerged as a therapeutic strategy to treat cognitive impairment in early Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28012176", "endSection": "abstract" }, { "offsetInBeginSection": 1622, "offsetInEndSection": 1858, "text": "UE2343 is safe, well tolerated and reaches the brain at concentrations predicted to inhibit 11\u03b2-HSD1. UE2343 is therefore a suitable candidate to test the hypothesis that 11\u03b2-HSD1 inhibition in brain improves memory in patients with AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28012176", "endSection": "abstract" } ] }, { "body": "Can nrf2 activation lead to resistance to radiotherapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25159739", "http://www.ncbi.nlm.nih.gov/pubmed/29500295", "http://www.ncbi.nlm.nih.gov/pubmed/24078215", "http://www.ncbi.nlm.nih.gov/pubmed/25717032" ], "ideal_answer": [ "Resistance to chemoradiotherapy is a major obstacle to successful treatment of glioblastoma. Recently, the role of NF-E2-related factor 2 (Nrf2) in enhancing chemoradiation sensitivity has been reported in several types of cancers. Blocking Nrf2 activation may be a promising method enhancing chemoradiation sensitivity of glioblastoma cells." ], "type": "summary", "id": "5e4b4be26d0a27794100001a", "snippets": [ { "offsetInBeginSection": 1374, "offsetInEndSection": 1450, "text": "NRF2 appeared to play a role in CSC survival and anticancer drug resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25717032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Resistance to chemoradiotherapy is a major obstacle to successful treatment of glioblastoma. Recently, the role of NF-E2-related factor 2 (Nrf2) in enhancing chemoradiation sensitivity has been reported in several types of cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078215", "endSection": "abstract" }, { "offsetInBeginSection": 1395, "offsetInEndSection": 1615, "text": "The activation of Nrf2 may be associate with enhancing chemoradiation sensitivity in human glioblastoma cell. Blocking Nrf2 activation may be a promising method enhancing chemoradiation sensitivity of glioblastoma cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078215", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1289, "text": "Our study confirmed the antagonistic roles of curcumin to counteract radiation-induced cerebral injury in vivo and suggested that the potent Nrf2 activation capability might be valuable for the protective effects of curcumin against radiation. This provides a potential useful radioprotection dietary component for human populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25159739", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 633, "text": "We show that NUAK1 is activated by oxidative stress and that this activation is required to facilitate nuclear import of the antioxidant master regulator NRF2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29500295", "endSection": "abstract" } ] }, { "body": "Are there interactions between short and long noncoding RNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29749606" ], "ideal_answer": [ "Yes. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions.", "It is now evident that noncoding RNAs play key roles in regulatory networks determining cell fate and behavior, in a myriad of different conditions, and across all species. Among these noncoding RNAs are short RNAs, such as MicroRNAs, snoRNAs, and Piwi-interacting RNAs, and the functions of those are relatively well understood. Other noncoding RNAs are longer, and their modes of action and functions are also increasingly explored and deciphered. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions. LncRNAs serve as precursors for many types of small RNAs and, therefore, the pathways for small RNA biogenesis can impinge upon the fate of lncRNAs. In addition, lncRNA expression can be repressed by small RNAs, and lncRNAs can affect small RNA activity and abundance through competition for binding or by triggering small RNA degradation.", "Yes. Short RNAs and long noncoding RNAs interact with each other with reciprocal consequences for their fates and functions." ], "exact_answer": "yes", "type": "yesno", "id": "5e46fda33f54159529000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1078, "text": "It is now evident that noncoding RNAs play key roles in regulatory networks determining cell fate and behavior, in a myriad of different conditions, and across all species. Among these noncoding RNAs are short RNAs, such as MicroRNAs, snoRNAs, and Piwi-interacting RNAs, and the functions of those are relatively well understood. Other noncoding RNAs are longer, and their modes of action and functions are also increasingly explored and deciphered. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions. LncRNAs serve as precursors for many types of small RNAs and, therefore, the pathways for small RNA biogenesis can impinge upon the fate of lncRNAs. In addition, lncRNA expression can be repressed by small RNAs, and lncRNAs can affect small RNA activity and abundance through competition for binding or by triggering small RNA degradation. Here, I review the known types of interactions between small and long RNAs, discuss their outcomes, and bring representative examples from studies in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749606", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 579, "text": "Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749606", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 580, "text": "Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29749606", "endSection": "abstract" } ] }, { "body": "Which molecule is inhibited by encorafenib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "http://www.ncbi.nlm.nih.gov/pubmed/27116335", "http://www.ncbi.nlm.nih.gov/pubmed/31114933", "http://www.ncbi.nlm.nih.gov/pubmed/28640105", "http://www.ncbi.nlm.nih.gov/pubmed/29326440", "http://www.ncbi.nlm.nih.gov/pubmed/30122982", "http://www.ncbi.nlm.nih.gov/pubmed/30018031", "http://www.ncbi.nlm.nih.gov/pubmed/28277830", "http://www.ncbi.nlm.nih.gov/pubmed/29568360", "http://www.ncbi.nlm.nih.gov/pubmed/29356698", "http://www.ncbi.nlm.nih.gov/pubmed/26673799", "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "http://www.ncbi.nlm.nih.gov/pubmed/29903896", "http://www.ncbi.nlm.nih.gov/pubmed/26586345", "http://www.ncbi.nlm.nih.gov/pubmed/29573941", "http://www.ncbi.nlm.nih.gov/pubmed/28611198", "http://www.ncbi.nlm.nih.gov/pubmed/29210065", "http://www.ncbi.nlm.nih.gov/pubmed/29155017", "http://www.ncbi.nlm.nih.gov/pubmed/30117021" ], "ideal_answer": [ "Encorafenib is a BRAF inhibitor. It is a promising therapy for metastatic or inoperable melanoma with a BRAF mutation." ], "exact_answer": [ "BRAF" ], "type": "factoid", "id": "5e319789fbd6abf43b00004a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Encorafenib (LGX818) is a promising BRAFV600E inhibitor that has efficacy against metastatic melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155017", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 915, "text": "Using patient- and in vivo-derived melanoma cell lines with acquired BRAFi resistance, we show that combined treatment with the BRAFi encorafenib and HDACi panobinostat in 2D and 3D culture systems synergistically induced caspase-dependent apoptotic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29210065", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1184, "text": "Importantly, combination of the BRAF inhibitors (BRAFi) vemurafenib (PLX4032), dabrafenib, or encorafenib with inhibitors dually targeting the EGFR and HER2 (such as lapatinib, canertinib, and afatinib) significantly reduced the metabolic activity and proliferative potential of CRC cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29326440", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "PURPOSE OF REVIEW: To describe the pharmacological properties, preclinical and clinical data of the novel V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF)-inhibitor encorafenib (LGX818) and to compare these with established BRAF-inhibitors in the treatment of locally advanced or metastatic melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29356698", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 326, "text": "We investigated encorafenib, a BRAF inhibitor with unique target-binding properties, alone or in combination with the MEK inhibitor binimetinib, versus vemurafenib in patients with advanced BRAFV600-mutant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29573941", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 777, "text": "In this study, we identify the antifolate methotrexate (MTX) as a sensitizer of acquired- and intrinsically-resistant MM cells to BRAFi's dabrafenib and encorafenib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568360", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 949, "text": "We assembled a panel of melanoma cell lines with class IIa (activation segment) or IIb (p-loop) mutations and compared these with WT or V600E/K BRAF mutant cells. Cell lines and PDXs were treated with BRAFi (vemurafenib, dabrafenib, encorafenib, and LY3009120), MEKi (cobimetinib, trametinib, and binimetinib), or the combination. We identified 2 patients with BRAF L597S metastatic melanoma who were treated with dMAPKi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29903896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The FDA approved the BRAF/MEK inhibitor combination encorafenib/binimetinib for patients with metastatic or inoperable melanoma with a BRAF V600E or V600K mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30018031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Encorafenib (Braftovi\u2122), a BRAF inhibitor, and binimetinib (Mektovi\u00ae), a MEK inhibitor, are two orally bioavailable drugs developed by Array BioPharma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30117021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "title" }, { "offsetInBeginSection": 1354, "offsetInEndSection": 1491, "text": "Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1185, "text": "This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29573941", "endSection": "title" }, { "offsetInBeginSection": 3189, "offsetInEndSection": 3296, "text": "Encorafenib plus binimetinib could represent a new treatment option for patients with BRAF-mutant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29573941", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 599, "text": "Areas covered: Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/MEK inhibitor combinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586345", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 884, "text": "Expert Opinion: While other BRAF/MEK inhibitor combinations have achieved a median overall survival (OS) of 22 months, patients with advanced BRAF mutation-positive melanoma treated with encorafenib plus binimetinib achieved a median OS of 33.6 months in the phase III COLUMBUS trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Encorafenib (LGX818) is a promising BRAF __sup__ V600E __end_sup__ inhibitor that has efficacy against metastatic melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Purpose: Encorafenib, a selective BRAF inhibitor (BRAFi), has a pharmacologic profile that is distinct from that of other clinically active BRAFis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Development of encorafenib for BRAF-mutated advanced melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29356698", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "endSection": "title" }, { "offsetInBeginSection": 288, "offsetInEndSection": 415, "text": "Encorafenib (LGX-818, Braftovi) and binimetinib (MEK-162, Mektovi) are small-molecule inhibitors of BRAF and MEK, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 432, "text": "Encorafenib ( LGX-818 , Braftovi ) and binimetinib ( MEK-162 , Mektovi ) are small-molecule inhibitors of BRAF and MEK , respectively . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 566, "text": "With advances in RAF inhibitors and second-generation inhibitors including encorafenib and vemurafenib , which have been approved for treating BRAF-V600E malignancies , the combinatorial therapeutic strategies of RAF inhibitors elicit remarkable responses in patients with BRAF-V600E mCRC . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30122982", "endSection": "abstract" }, { "offsetInBeginSection": 921, "offsetInEndSection": 1157, "text": "This improved efficacy may be related to the distinct pharmacokinetics of encorafenib , with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 776, "text": "Of these inhibitors , encorafenib and binimetinib are the newest combination , which received approval by the Food and Drug Administration ( FDA ) for the treatment of BRAF V600E/K-mutated melanoma in June 2018 . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Encorafenib, a new-generation BRAF inhibitor, has been approved by FDA for the treatment of melanoma in combination with binimetinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31114933", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 416, "text": "Encorafenib (LGX-818, Braftovi) and binimetinib (MEK-162, Mektovi) are small-molecule inhibitors of BRAF and MEK, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 754, "text": "Of these inhibitors, encorafenib and binimetinib are the newest combination, which received approval by the Food and Drug Administration (FDA) for the treatment of BRAF V600E/K-mutated melanoma in June 2018.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 910, "text": "This review will focus on the preclinical pharmacology, pharmacokinetics and clinical utility of encorafenib and binimetinib in BRAF V600-mutated melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586345", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586345", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1150, "text": "This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 849, "text": "Expert opinion: While other BRAF/MEK inhibitor combinations have achieved a median overall survival (OS) of 22\u00a0months, patients with advanced BRAF mutation-positive melanoma treated with encorafenib plus binimetinib achieved a median OS of 33.6\u00a0months in the phase III COLUMBUS trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 564, "text": "Areas covered: Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/MEK inhibitor combinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 908, "text": "We report three male patients with metastatic BRAFV600E-mutated melanoma who developed pyogenic granulomas 16, 10, and 12 weeks after treatment initiation with the selective BRAF inhibitors vemurafenib or encorafenib (LGX818).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27116335", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 763, "text": "Treatment started in November 2015, with Encorafenib and Binimetinib, new BRAF and MEK inhibitors, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28640105", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 1052, "text": "Second-line efficacy of the pan-PI3K inhibitor BKM120 with either BRAF (encorafenib)/MEK (binimetinib) inhibitor combination or the ERK inhibitor VX-11e was confirmed in vivo Amplification of MET was observed in 3 PDX models, a higher frequency than expected and a possible novel mechanism of resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673799", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 619, "text": "Areas covered: A brief review of current BRAF, NRAS, and C-KIT inhibitors provides background for a thorough review of newly developed agents namely binimetinib, a MEK inhibitor, encorafenib a BRAF inhibitor, and masitinib which inhibits C-KIT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28277830", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1081, "text": "Results: Preclinical data demonstrated that encorafenib inhibited BRAF V600E kinase activity with a prolonged off-rate and suppressed proliferation and tumor growth of BRAF V600E-mutant melanoma models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611198", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1149, "text": "This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611198", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Purpose: Encorafenib, a selective BRAF inhibitor (BRAFi), has a pharmacologic profile that is distinct from that of other clinically active BRAFis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611198", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 267, "text": "We evaluated encorafenib in a phase I study in patients with BRAFi treatment-na\u00efve and pretreated BRAF-mutant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611198", "endSection": "abstract" } ] }, { "body": "What is the basis of the capture Hi-C experimental protocol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25938943", "http://www.ncbi.nlm.nih.gov/pubmed/26616563", "http://www.ncbi.nlm.nih.gov/pubmed/25695508", "http://www.ncbi.nlm.nih.gov/pubmed/29531215", "http://www.ncbi.nlm.nih.gov/pubmed/25122612", "http://www.ncbi.nlm.nih.gov/pubmed/29979818", "http://www.ncbi.nlm.nih.gov/pubmed/30224643", "http://www.ncbi.nlm.nih.gov/pubmed/30010637" ], "ideal_answer": [ "Capture Hi-C (CHi-C) allows high-resolution analysis of targeted regions of the genome by incorporating a sequence capture step into a Hi-C protocol. Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of biologically significant chromatin interactions compared to conventional Hi-C, for an equivalent number of sequence reads", "Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts.", "Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. To address this, Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of biologically significant chromatin interactions compared to conventional Hi-C, for an equivalent number of sequence reads We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines. We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment. Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas7,8 Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types. ", "Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. Here we develop a capture Hi-C (cHi-C) approach to allow an agnostic characterization of these physical interactions on a genome-wide scale. Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types.", "Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types. Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas7,8 To address this, Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of biologically significant chromatin interactions compared to conventional Hi-C, for an equivalent number of sequence reads We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment. Here, we use Capture Hi-C (CHi-C) to annotate 63 loci; we identify 110 putative target genes at 33 loci." ], "type": "summary", "id": "5cf4ea83a49efeb44c00000d", "snippets": [ { "offsetInBeginSection": 270, "offsetInEndSection": 453, "text": " We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616563", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 274, "text": "Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25695508", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 608, "text": "Here we develop a capture Hi-C (cHi-C) approach to allow an agnostic characterization of these physical interactions on a genome-wide scale. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25695508", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 614, "text": "Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25122612", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 470, "text": "Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25938943", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 561, "text": "Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas7,8", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30224643", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 915, "text": "To address this, Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of biologically significant chromatin interactions compared to conventional Hi-C, for an equivalent number of sequence reads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29979818", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 738, "text": "We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30010637", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 394, "text": "Here, we use Capture Hi-C (CHi-C) to annotate 63 loci; we identify 110 putative target genes at 33 loci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29531215", "endSection": "abstract" } ] }, { "body": "What is the role of Scc2/Nipbl?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28914604" ], "ideal_answer": [ "Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes. Scc2 also binds dynamically to chromatin, principally through an association with cohesin. Scc2's movement within chromatin is consistent with a 'stop-and-go' or 'hopping' motion. A low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading." ], "type": "summary", "id": "5e49bcce6d0a27794100000f", "snippets": [ { "offsetInBeginSection": 251, "offsetInEndSection": 1040, "text": "Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes. However, it is possible that the stimulation of cohesin's ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking in human cells, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2's movement within chromatin is consistent with a 'stop-and-go' or 'hopping' motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28914604", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 356, "text": "Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28914604", "endSection": "abstract" } ] }, { "body": "What is the chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15717219", "http://www.ncbi.nlm.nih.gov/pubmed/9016531", "http://www.ncbi.nlm.nih.gov/pubmed/10764678", "http://www.ncbi.nlm.nih.gov/pubmed/7585875" ], "ideal_answer": [ "Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic disorder resulting in advanced vascular atherosclerosis and premature death, primarily from coronary artery disease. The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19", "Mutations in the LDLr gene (LDLR), which is located on chromosome 19, cause familial hypercholesterolemia", "The chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia is chromosome 19q13.3.", "Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic disorder resulting in advanced vascular atherosclerosis and premature death, primarily from coronary artery disease. The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19.", "The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19." ], "exact_answer": [ "short arm of chromosome 19" ], "type": "factoid", "id": "5e31cceafbd6abf43b000052", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic disorder resulting in advanced vascular atherosclerosis and premature death, primarily from coronary artery disease. The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15717219", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 198, "text": "Mutations in the LDLr gene (LDLR), which is located on chromosome 19, cause familial hypercholesterolemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9016531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Chromosome 19 is short but has higher relative density of genes than other chromosomes. Increasing number of the genes coding for proteins implicated in the pathogenesis of various human diseases have been mapped on chromosome 19. Mutations of low density lipoprotein receptor (LDL-R) result in one of the most frequent mendelian inherited disorder-familial hypercholesterolemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7585875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Clinical familial hypercholesterolemia has been shown to result from mutations in 2 genes, the low density lipoprotein (LDL) receptor on chromosome 19 and apolipoprotein B on chromosome 2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10764678", "endSection": "abstract" } ] }, { "body": "Can brain derived exosomes carry APP molecules?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29277576", "http://www.ncbi.nlm.nih.gov/pubmed/28956068", "http://www.ncbi.nlm.nih.gov/pubmed/18171695", "http://www.ncbi.nlm.nih.gov/pubmed/28184302" ], "ideal_answer": [ "Yes,\nsmall lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP" ], "exact_answer": "yes", "type": "yesno", "id": "5e5b90b3752ebcdc7a000002", "snippets": [ { "offsetInBeginSection": 320, "offsetInEndSection": 455, "text": "Here, we show that small lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28956068", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 702, "text": "these exosomes contained APP and were capable of efficiently transferring APP to normal primary neurons. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29277576", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 779, "text": "Accumulating evidence has demonstrated that exosomes are associated with amyloid precursor (APP) and Tau proteins and play a controversial role in Alzheimer's disease process. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28184302", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 586, "text": " Here we have investigated the role of exosomes in the processing of APP and show that these vesicles contain APP-CTFs, as well as Abeta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18171695", "endSection": "abstract" } ] }, { "body": "List the most common cancers after a radiation exposure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8896256", "http://www.ncbi.nlm.nih.gov/pubmed/28535153", "http://www.ncbi.nlm.nih.gov/pubmed/7480642", "http://www.ncbi.nlm.nih.gov/pubmed/25034478", "http://www.ncbi.nlm.nih.gov/pubmed/11309438", "http://www.ncbi.nlm.nih.gov/pubmed/25088201" ], "ideal_answer": [ "well-known increase in leukaemia, increases in solid cancer such as cancers of the lung, breast, stomach and thyroid have also been demonstrated." ], "exact_answer": [ [ "leukaemia" ], [ "lung cancer" ], [ "breast cancer" ], [ "stomach cancer" ], [ "thyroid cancer" ] ], "type": "list", "id": "5e48100bd14c9f295d000007", "snippets": [ { "offsetInBeginSection": 182, "offsetInEndSection": 205, "text": " lethal skin carcinomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7480642", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 789, "text": " leukemia (1952)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7480642", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 1231, "text": "esides the well-known increase in leukaemia, increases in solid cancer such as cancers of the lung, breast, stomach and thyroid have also been demonstrated. Radiation-induced leukaemia occurred 2 to 3 years after exposure, reached its peak within 6 to 8 years after the bombing, and has since declined steadily. However, this has not been true of solid cancer. Radiation-induced solid cancer begins to appear at later ages than such cancer is normally prone to develop, and continues to increase proportionally with the increase in mortality or incidence in the control group as it ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8896256", "endSection": "abstract" } ] }, { "body": "Which are the main G1/S transcription factors in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21257795", "http://www.ncbi.nlm.nih.gov/pubmed/10512874", "http://www.ncbi.nlm.nih.gov/pubmed/23382076", "http://www.ncbi.nlm.nih.gov/pubmed/28505153", "http://www.ncbi.nlm.nih.gov/pubmed/29792825" ], "ideal_answer": [ "MBF/SBF is the major transcriptional repressor of G1/S genes in Saccharomyces cerevisiae.", "The G(1)/S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively.", "MBF and SBF are two members of bHLH-PAS-containing family of transcription factors that represent theG1/S transcription factors in Saccharomyces cerevisiae", "We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1-S transcription factor DSC1/MBF In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair.", "To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair.", "To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast.", "MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1- S transcription factor DSC1/ MBF. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair.", "MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1-S transcription factor DSC1/MBF. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair.", "To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. The G(1)/S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe", "In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair. MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively." ], "exact_answer": [ [ "SBF complex" ], [ "MBF complex" ], [ "Skn7" ] ], "type": "list", "id": "5cf0f567a49efeb44c00000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 425, "text": "To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29792825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1-S transcription factor DSC1/MBF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10512874", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 468, "text": "To gain more insight into the G(1)/S circuitry, we characterized Swi6p, Swi4p and Mbp1p, the closest orthologues of SBF (Swi6p and Swi4p) and MBF (Swi6p and Mbp1p) components in S. cerevisiae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21257795", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The G(1)/S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21257795", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382076", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 374, "text": " MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382076", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 636, "text": "Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28505153", "endSection": "abstract" } ] }, { "body": "What is Hemochromatosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29154924", "http://www.ncbi.nlm.nih.gov/pubmed/28902419", "http://www.ncbi.nlm.nih.gov/pubmed/29454332", "http://www.ncbi.nlm.nih.gov/pubmed/12091366", "http://www.ncbi.nlm.nih.gov/pubmed/11517631", "http://www.ncbi.nlm.nih.gov/pubmed/19342478", "http://www.ncbi.nlm.nih.gov/pubmed/22099368", "http://www.ncbi.nlm.nih.gov/pubmed/18293685", "http://www.ncbi.nlm.nih.gov/pubmed/24054178", "http://www.ncbi.nlm.nih.gov/pubmed/20609690", "http://www.ncbi.nlm.nih.gov/pubmed/25075539", "http://www.ncbi.nlm.nih.gov/pubmed/28541873", "http://www.ncbi.nlm.nih.gov/pubmed/23418762", "http://www.ncbi.nlm.nih.gov/pubmed/29134618", "http://www.ncbi.nlm.nih.gov/pubmed/29423808" ], "ideal_answer": [ "Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy.", "Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism that may lead to iron overload." ], "type": "summary", "id": "5e31cc3cfbd6abf43b000051", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Hereditary hemochromatosis (HH) is one of the most common genetically transmitted conditions in individuals of Northern European ancestry. The disease is characterized by excessive intestinal absorption of dietary iron, resulting in pathologically high iron storage in tissues and organs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29423808", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 128, "text": "HFE hemochromatosis is an inborn error of iron metabolism linked to a defect in the regulation of hepcidin synthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29454332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29134618", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 247, "text": "hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29154924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism that may lead to iron overload.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28902419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "OBJECTIVE\n\nHemochromatosis is an inherited disease with iron overload and joint involvement resembling osteoarthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20609690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Hereditary hemochromatosis is an autosomal recessive disorder that disturbs iron metabolism and results in iron deposition throughout the body . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28541873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Hereditary hemochromatosis is an inherited disorder of iron metabolism in the Caucasian population with an autosomal recessive inheritance and a prevalence between 1 in 200 and 1 in 500 . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18293685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Hereditary hemochromatosis is a disorder that can cause iron overload and organ damage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24054178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12091366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Hereditary hemochromatosis is an iron overload disorder that can lead to the impairment of multiple organs and is caused by mutations in one or more different genes . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19342478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Hereditary hemochromatosis is an autosomal recessive disorder that disrupts the body's regulation of iron.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23418762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Hereditary hemochromatosis type 1, also known as hereditary hemochromatosis classical (HHC), is an iron overload disorder associated, in most cases, with mutations of the hemochromatosis (HFE) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22099368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Hereditary hemochromatosis (HH) is a disorder of iron regulation that leads to excessive iron absorption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11517631", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 212, "text": "The primary cause of excessive iron storage in humans is hereditary hemochromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25075539", "endSection": "abstract" } ] }, { "body": "What molecules are the multidrug transporter MDR3 targeting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30222019", "http://www.ncbi.nlm.nih.gov/pubmed/30079523", "http://www.ncbi.nlm.nih.gov/pubmed/29895698" ], "ideal_answer": [ "Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator." ], "exact_answer": [ "Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator" ], "type": "factoid", "id": "5e5b626fb761aafe0900000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30222019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "The multiple drug resistance 3 (MDR3) protein is a canalicular phospholipid translocator", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The ATP-binding cassette transporter ABCB4/MDR3 is critical for biliary phosphatidylcholine (PC) excretion ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29895698", "endSection": "abstract" } ] }, { "body": "What is the role of the Hof1-Cyk3 interaction in yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29321253" ], "ideal_answer": [ "In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1 contribute to septum formation and cytokinesis. There is also evidence that they interact physically.", "In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1 contribute to septum formation and cytokinesis. Hof1 and Cyk3 interact physically and the interaction 1) is mediated by a direct binding of the Hof1 SH3 domain to a proline-rich motif in Cyk3; 2) occurs specifically at the time of cytokinesis but is independent of the (hyper)phosphorylation of both proteins that occurs at about the same time; 3) is dispensable for the normal localization of both proteins; 4) is essential for normal primary-septum formation and a normal rate of cleavage-furrow ingression; and 5) becomes critical for growth when either Inn1 or the type II myosin Myo1 (a key component of the contractile actomyosin ring) is absent. The similarity in phenotype between cyk3[?] mutants and mutants specifically lacking the Hof1-Cyk3 interaction suggests that the interaction is particularly important for Cyk3 function, but it may be important for Hof1 function as well." ], "type": "summary", "id": "5e36de90b5b409ea5300000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Role of the Hof1-Cyk3 interaction in cleavage-furrow ingression and primary-septum formation during yeast cytokinesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321253", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1294, "text": "In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1 contribute to septum formation and cytokinesis. Because hof1\u2206 and cyk3\u2206 single mutants have relatively mild defects but hof1\u2206 cyk3\u2206 double mutants are nearly dead, it has been hypothesized that these proteins contribute to parallel pathways. However, there is also evidence that they interact physically. In this study, we examined this interaction and its functional significance in detail. Our data indicate that the interaction 1) is mediated by a direct binding of the Hof1 SH3 domain to a proline-rich motif in Cyk3; 2) occurs specifically at the time of cytokinesis but is independent of the (hyper)phosphorylation of both proteins that occurs at about the same time; 3) is dispensable for the normal localization of both proteins; 4) is essential for normal primary-septum formation and a normal rate of cleavage-furrow ingression; and 5) becomes critical for growth when either Inn1 or the type II myosin Myo1 (a key component of the contractile actomyosin ring) is absent. The similarity in phenotype between cyk3\u2206 mutants and mutants specifically lacking the Hof1-Cyk3 interaction suggests that the interaction is particularly important for Cyk3 function, but it may be important for Hof1 function as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321253", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1294, "text": "The similarity in phenotype between cyk3\u2206 mutants and mutants specifically lacking the Hof1-Cyk3 interaction suggests that the interaction is particularly important for Cyk3 function, but it may be important for Hof1 function as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321253", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1295, "text": "The similarity in phenotype between cyk3\u2206 mutants and mutants specifically lacking the Hof1-Cyk3 interaction suggests that the interaction is particularly important for Cyk3 function, but it may be important for Hof1 function as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321253", "endSection": "abstract" } ] }, { "body": "List features of the SAM syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31106887", "http://www.ncbi.nlm.nih.gov/pubmed/23974871", "http://www.ncbi.nlm.nih.gov/pubmed/27154412", "http://www.ncbi.nlm.nih.gov/pubmed/26073755", "http://www.ncbi.nlm.nih.gov/pubmed/29604126", "http://www.ncbi.nlm.nih.gov/pubmed/25041099" ], "ideal_answer": [ "SAM syndrome is characterized by severe dermatitis, multiple allergies and metabolic wasting. It is caused by mutations in the desmoglein 1 gene (DSG1)." ], "exact_answer": [ [ "severe dermatitis" ], [ "multiple allergies" ], [ "metabolic wasting" ] ], "type": "list", "id": "5e30ee25fbd6abf43b00003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Severe skin dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a rare life-threatening inherited condition caused by bi-allelic mutations in DSG1 encoding desmoglein 1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29604126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Recently, homozygous mutations in the desmoglein-1 (DSG1) gene and heterozygous mutation in the desmoplakin (DSP) gene have been demonstrated to be associated with severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome (Mendelian Inheritance in Man no. 615508).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27154412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "Monoallelic desmoglein 1 mutations have been known for many years to cause striate palmoplantar keratoderma, but only recently, biallelic loss-of-function mutations were associated with a new disorder, designated as SAM syndrome (comprising severe dermatitis, multiple allergies and metabolic wasting) in two consanguineous families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25041099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND: Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 gene (DSG1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26073755", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 304, "text": "Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23974871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31106887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome caused by de novo mutation in the DSP gene misdiagnosed as generalized pustular psoriasis and treatment of acitretin with gabapentin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31106887", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31106887", "endSection": "abstract" } ] }, { "body": "What does the Smith\u2013Waterman algorithm do?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11301301", "http://www.ncbi.nlm.nih.gov/pubmed/28432608", "http://www.ncbi.nlm.nih.gov/pubmed/26445214" ], "ideal_answer": [ "The Smith-Waterman algorithm performs local sequence alignments. " ], "type": "summary", "id": "5e360b81158f994d3a000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The Smith-Waterman (SW) algorithm based on dynamic programming is a well-known classical method for high precision sequence matching and has become the gold standard to evaluate sequence alignment software. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28432608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND\n\nThe Smith-Waterman algorithm is known to be a more sensitive approach than heuristic algorithms for local sequence alignment algorithms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26445214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND\nThe Smith-Waterman algorithm is known to be a more sensitive approach than heuristic algorithms for local sequence alignment algorithms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26445214", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 578, "text": "The Smith-Waterman algorithm finds the local alignment with maximal score but it is unable to find local alignment with maximum degree of similarity (e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The Smith-Waterman algorithm for local sequence alignment is one of the most important techniques in computational molecular biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The Smith-Waterman algorithm for local sequence alignment is one of the most important techniques in computational molecular biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301301", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 577, "text": "The Smith-Waterman algorithm finds the local alignment with maximal score but it is unable to find local alignment with maximum degree of similarity (e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301301", "endSection": "abstract" } ] }, { "body": "Is SATB1 positioned close to AT-rich sequences?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24729451", "http://www.ncbi.nlm.nih.gov/pubmed/24047082", "http://www.ncbi.nlm.nih.gov/pubmed/18408014", "http://www.ncbi.nlm.nih.gov/pubmed/28179318", "http://www.ncbi.nlm.nih.gov/pubmed/24118100", "http://www.ncbi.nlm.nih.gov/pubmed/10629043", "http://www.ncbi.nlm.nih.gov/pubmed/8049444", "http://www.ncbi.nlm.nih.gov/pubmed/29306014", "http://www.ncbi.nlm.nih.gov/pubmed/9548713", "http://www.ncbi.nlm.nih.gov/pubmed/27590341" ], "ideal_answer": [ "Yes, SATB1 is preferentially located at the start of an AT-rich sequence and is associated with other, more diffuse AT- rich sequences in the genome.", "Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein expressed predominantly in thymocytes, recognizes an ATC sequence context that consists of a cluster of sequence stretches with well-mixed A's, T's, and C's without G's on one strand. SATB1 (special AT-rich sequence-binding protein-1) provides a key link between DNA loop organization, chromatin modification/remodeling, and association of transcription factors at matrix attachment regions (MARs).", "Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein expressed predominantly in thymocytes, recognizes an ATC sequence context that consists of a cluster of sequence stretches with well-mixed A's, T's, and C's without G's on one strand.", "We have purified and identified one of the core factors as the matrix attachment region (MAR) binding protein, SATB1, which is known to bind to AT-rich sequences with a high propensity to unwind" ], "exact_answer": "yes", "type": "yesno", "id": "5d38826ea1e1595105000016", "snippets": [ { "offsetInBeginSection": 416, "offsetInEndSection": 585, "text": " Tryptic cleavage and peptide sequence analysis demonstrated that the 98-kD protein is identical to a recently cloned protein, special A-T-rich binding protein 1 (SATB1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8049444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein expressed predominantly in thymocytes, recognizes an ATC sequence context that consists of a cluster of sequence stretches with well-mixed A's, T's, and C's without G's on one strand. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9548713", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 973, "text": " We have purified and identified one of the core factors as the matrix attachment region (MAR) binding protein, SATB1, which is known to bind to AT-rich sequences with a high propensity to unwind", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10629043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "SATB1 (special AT-rich sequence-binding protein-1) provides a key link between DNA loop organization, chromatin modification/remodeling, and association of transcription factors at matrix attachment regions (MARs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18408014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24047082", "endSection": "title" }, { "offsetInBeginSection": 13, "offsetInEndSection": 133, "text": "pecial AT rich sequence binding protein 1 (SATB1) plays a crucial role in the biology of various types of human cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24047082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Loss of special AT-rich sequence-binding protein 1 (SATB1)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24118100", "endSection": "title" }, { "offsetInBeginSection": 5, "offsetInEndSection": 164, "text": "Special AT-rich sequence-binding protein 1 (SATB1) is a cell type-specific matrix attachment region binding protein, functioning as a global genome organizer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24118100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "SATB1 (special AT-rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24729451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Special AT-rich Sequence-binding Protein 1 (SATB1) Functions as an Accessory Factor in Base Excision Repair.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27590341", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Rearrangement of the Chromatin Organizer Special AT-rich Binding Protein 1 Gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28179318", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "The Special AT-rich Sequence Binding Protein 1 (SATB1) exerts multiple functions, by influencing the structural organization of chromatin and interacting with several co-activators and co-repressors of transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29306014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The Special AT-rich Sequence Binding Protein 1 (SATB1) and its role in solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29306014", "endSection": "title" } ] }, { "body": "Describe the Java Adverse Drug Event (JADE) tool", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "http://www.ncbi.nlm.nih.gov/pubmed/20465815" ], "ideal_answer": [ "The Java Adverse Drug event (Jade) is a tool for medical researchers to explore adverse drug events using health insurance plans and drug-drug interactions.", "The Java Adverse Drug Event (JADE) tool enables the analysis of prescribed drugs in connection with diagnoses from hospital stays. It can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information." ], "type": "summary", "id": "5e36e51ab5b409ea53000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "JADE: a tool for medical researchers to explore adverse drug events using health claims data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 985, "text": "The objective of our project was to create a tool for physicians to explore health claims data with regard to adverse drug reactions. The Java Adverse Drug Event (JADE) tool should enable the analysis of prescribed drugs in connection with diagnoses from hospital stays.METHODS: We calculated the number of days drugs were taken by using the defined daily doses and estimated possible interactions between dispensed drugs using the Austria Codex, a database including drug-drug interactions. The JADE tool was implemented using Java, R and a PostgreSQL database.RESULTS: Beside an overview of the study cohort which includes selection of gender and age groups, selected statistical methods like association rule learning, logistic regression model and the number needed to harm have been implemented.CONCLUSION: The JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 281, "text": "The Java Adverse Drug Event (JADE) tool should enable the analysis of prescribed drugs in connection with diagnoses from hospital stays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 991, "text": "CONCLUSION\n\nThe JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 984, "text": "CONCLUSION The JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 281, "text": "The Java Adverse Drug Event (JADE) tool should enable the analysis of prescribed drugs in connection with diagnoses from hospital stays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 991, "text": "CONCLUSION\nThe JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 985, "text": "CONCLUSION: The JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 947, "text": "The JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298803", "endSection": "abstract" } ] }, { "body": "Which drugs were tested in the CheckMate 227 clinical trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29661758", "http://www.ncbi.nlm.nih.gov/pubmed/29658845", "http://www.ncbi.nlm.nih.gov/pubmed/30393621", "http://www.ncbi.nlm.nih.gov/pubmed/27610613", "http://www.ncbi.nlm.nih.gov/pubmed/31066582", "http://www.ncbi.nlm.nih.gov/pubmed/31195357" ], "ideal_answer": [ "CheckMate-227 clinical trial tested ipilimumab plus nivolumab for the treatment of non-small cell lung cancer." ], "exact_answer": [ [ "ipilimumab" ], [ "nivolumab" ] ], "type": "list", "id": "5e30f12afbd6abf43b000041", "snippets": [ { "offsetInBeginSection": 1829, "offsetInEndSection": 2019, "text": "The rate of grade 3 or 4 treatment-related adverse events was 31.2% with nivolumab plus ipilimumab and 36.1% with chemotherapy. ical; CheckMate 227 ClinicalTrials.gov number, NCT02477826 .).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29658845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "The first data from the phase III CheckMate-227 trial of ipilimumab plus nivolumab for the treatment of non-small cell lung cancer suggests that the two drugs boost progression-free survival in patients with a high tumor mutation burden. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29661758", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1198, "text": "Most recently, two phase III first-line NSCLC studies have provided evidence that tumour mutational burden (TMB) correlates with the clinical response to the combination of nivolumab and ipilimumab (CheckMate-227; NCT02477826), whereas atezolizumab response was correlated with T effector gene signature expression (IMPower 150; NCT02366143). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30393621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31195357", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "BACKGROUND\n\nIn the phase III CheckMate 227 study, first-line nivolumab\u00a0+\u00a0ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; \u226510 mutations/megabase).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31195357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "The first data from the phase III CheckMate-227 trial of ipilimumab plus nivolumab for the treatment of non-small cell lung cancer suggests that the two drugs boost progression-free survival in patients with a high tumor mutation burden.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29661758", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 451, "text": "In this Review, we examine the potential role of dual immune checkpoint inhibition with nivolumab plus ipilimumab in the management of patients with previously untreated advanced non-small-cell lung cancer, based on results from the Phase III CheckMate 227 study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31066582", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "BACKGROUND\nIn the phase III CheckMate 227 study, first-line nivolumab\u00a0+\u00a0ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; \u226510 mutations/megabase).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31195357", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1198, "text": "Most recently, two phase III first-line NSCLC studies have provided evidence that tumour mutational burden (TMB) correlates with the clinical response to the combination of nivolumab and ipilimumab (CheckMate-227; NCT02477826), whereas atezolizumab response was correlated with T effector gene signature expression (IMPower 150; NCT02366143).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30393621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "The first data from the phase III CheckMate-227 trial of ipilimumab plus nivolumab for the treatment of non-small cell lung cancer suggests that the two drugs boost progression-free survival in patients with a high tumor mutation burden.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29661758", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1197, "text": "Most recently, two phase III first-line NSCLC studies have provided evidence that tumour mutational burden (TMB) correlates with the clinical response to the combination of nivolumab and ipilimumab (CheckMate-227; NCT02477826), whereas atezolizumab response was correlated with T effector gene signature expression (IMPower 150; NCT02366143).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30393621", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 450, "text": "In this Review, we examine the potential role of dual immune checkpoint inhibition with nivolumab plus ipilimumab in the management of patients with previously untreated advanced non-small-cell lung cancer, based on results from the Phase III CheckMate 227 study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31066582", "endSection": "abstract" } ] }, { "body": "What is known about PAI-1 in longevity in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15939070", "http://www.ncbi.nlm.nih.gov/pubmed/9108791", "http://www.ncbi.nlm.nih.gov/pubmed/29152572" ], "ideal_answer": [ "Plasminogen activator inhibitor-1 (PAI-1) has been shown to be a key component of the senescence-related secretome and a direct mediator of cellular senescence. In murine models of accelerated aging, genetic deficiency and targeted inhibition of PAI-1 protect against aging-like pathology and prolong life span. However, the role of PAI-1 in human longevity remains unclear.\n, in centenarians there was a significantly higher frequency of the 4G allele and of the homozygous 4G4G genotype associated with high PAI-1 levels. Since high PAI-1 is considered a predictor of recurrent myocardial infarction in young men, it is intriguing that the corresponding genetic marker is more frequent in centenarians who have escaped major age-related atherothrombotic disease and reached the extreme limits of human life. Homozygosity for the 4G allele, despite its association with impaired fibrinolysis, is compatible with successful aging." ], "type": "summary", "id": "5e5b9b96752ebcdc7a000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Plasminogen activator inhibitor-1 (PAI-1) has been shown to be a key component of the senescence-related secretome and a direct mediator of cellular senescence. In murine models of accelerated aging, genetic deficiency and targeted inhibition of PAI-1 protect against aging-like pathology and prolong life span. However, the role of PAI-1 in human longevity remains unclear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29152572", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1011, "text": "Our study indicates a causal effect of PAI-1 on human longevity, which may be mediated by alterations in metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29152572", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 993, "text": "PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15939070", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 1368, "text": "However, in centenarians there was a significantly higher frequency of the 4G allele and of the homozygous 4G4G genotype associated with high PAI-1 levels. Since high PAI-1 is considered a predictor of recurrent myocardial infarction in young men, it is intriguing that the corresponding genetic marker is more frequent in centenarians who have escaped major age-related atherothrombotic disease and reached the extreme limits of human life. Homozygosity for the 4G allele, despite its association with impaired fibrinolysis, is compatible with successful aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9108791", "endSection": "abstract" } ] }, { "body": "Does metformin alleviate atherosclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25552600", "http://www.ncbi.nlm.nih.gov/pubmed/17307426", "http://www.ncbi.nlm.nih.gov/pubmed/29878903", "http://www.ncbi.nlm.nih.gov/pubmed/25527624", "http://www.ncbi.nlm.nih.gov/pubmed/29499335", "http://www.ncbi.nlm.nih.gov/pubmed/29452166", "http://www.ncbi.nlm.nih.gov/pubmed/22672501", "http://www.ncbi.nlm.nih.gov/pubmed/28526884", "http://www.ncbi.nlm.nih.gov/pubmed/27737949" ], "ideal_answer": [ "Yes. Metformin has been shown to decrease frequency of atherosclerosis-associated adverse effects in statin-intolerant patients and to slow the pathogenesis of type 2 diabetes mellitus.", "Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission.", "Yes. Metformin has been shown to decrease frequency of atherosclerosis-associated adverse effects in statin-intolerant patients and to slow the pathogenesis of type 2 diabetes.", "Coupled with their proven good safety profile these findings could translate into a significant clinical benefit. Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses.", "Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory responses Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses.", "Yes. Metformin has been shown in a number of clinical trial to prevent and attenuate atherosclerosis.", "Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease. Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory response." ], "exact_answer": "yes", "type": "yesno", "id": "5d38462b7bc3fee31f000012", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 184, "text": "Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17307426", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1407, "text": "Demonstrating antiatherothrombotic properties of dipeptidyl peptidase-4 inhibitors on proven markers is of substantial clinical significance. Coupled with their proven good safety profile these findings could translate into a significant clinical benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22672501", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 95, "text": "pleiotropic benefits of metformin in attenuation of atherosclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25527624", "endSection": "title" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1140, "text": "Pleiotropic effects of metformin ameliorate atherosclerosis and vascular senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25527624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25552600", "endSection": "title" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1553, "text": "Metformin attenuated Ang-II-induced atheromatous plaque formation and aortic aneurysm in ApoE(-/-) mice partly by reducing monocyte infiltration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25552600", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 258, "text": "Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28526884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28526884", "endSection": "title" }, { "offsetInBeginSection": 1226, "offsetInEndSection": 1598, "text": " In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28526884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27737949", "endSection": "title" }, { "offsetInBeginSection": 236, "offsetInEndSection": 366, "text": "metformin abated the progression of diabetes-accelerated atherosclerosis by inhibiting mitochondrial fission in endothelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27737949", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1681, "text": "metformin attenuated the development of atherosclerosis by reducing Drp1-mediated mitochondrial fission in an AMPK-dependent manner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27737949", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 276, "text": "metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29878903", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 500, "text": "Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29878903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29499335", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory responses", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452166", "endSection": "title" }, { "offsetInBeginSection": 1605, "offsetInEndSection": 1759, "text": "Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452166", "endSection": "abstract" } ] }, { "body": "List side effects of radiation therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25141962", "http://www.ncbi.nlm.nih.gov/pubmed/26390925", "http://www.ncbi.nlm.nih.gov/pubmed/29947933", "http://www.ncbi.nlm.nih.gov/pubmed/29983028", "http://www.ncbi.nlm.nih.gov/pubmed/29953370" ], "ideal_answer": [ "radiation-induced tumors\nradiation necrosis\nmicroangiopathy\nprogressive leukencephalopathy\npneumonitis\ndisturbance of the blood-brain barrier\nradionecrosis of brain tissue\nradiogenic liver damage\nmucositis\ncolitis\nosteitis\nosteoradionecrosis\nmyositis\nRadiation-induced fibrosis\nAcute skin reactions" ], "exact_answer": [ [ "Acute skin reactions" ], [ "Radiation-induced fibrosis" ], [ "myositis" ], [ "osteoradionecrosis" ], [ "osteitis" ], [ "colitis" ], [ "mucositis" ], [ "radiogenic liver damage" ], [ "radionecrosis of brain tissue" ], [ "disturbance of the blood-brain barrier" ], [ "pneumonitis" ], [ "progressive leukencephalopathy" ], [ "radiation-induced tumors" ], [ "radiation necrosis" ], [ "microangiopathy" ] ], "type": "list", "id": "5e46f9683f54159529000010", "snippets": [ { "offsetInBeginSection": 161, "offsetInEndSection": 349, "text": "The known serious side effects of radiation therapy on the head or central nervous system are uncommon and include radiation necrosis, microangiopathy, and progressive leukencephalopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29953370", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 695, "text": "radiation-induced tumors, a majority of which are meningiomas, followed by radiation-induced gliomas (RIGs) and sarcomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29953370", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 792, "text": "Frequent radiation-induced tissue alterations found by imaging are pneumonitis, disturbance of the blood-brain barrier, radionecrosis of brain tissue, radiogenic liver damage, mucositis, colitis, osteitis, osteoradionecrosis and myositis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29947933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Radiation-induced second malignancies (RISM) is one of the important late side effects of radiation therapy and has an impact on optimal treatment decision-making. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29983028", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 114, "text": "Radiation-induced fibrosis (RIF) is one of the severe long-term side effects of radiation therapy (RT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26390925", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 225, "text": "Acute skin reactions are one of the most common side effects of radiation therapy,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25141962", "endSection": "abstract" } ] }, { "body": "Are CD8+ (cytotoxic) T cells and CD4+ Helper T cells generated in the thyroid and express the T-cell receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26301869", "http://www.ncbi.nlm.nih.gov/pubmed/25591463", "http://www.ncbi.nlm.nih.gov/pubmed/7904067", "http://www.ncbi.nlm.nih.gov/pubmed/1533274", "http://www.ncbi.nlm.nih.gov/pubmed/28382035", "http://www.ncbi.nlm.nih.gov/pubmed/29677476", "http://www.ncbi.nlm.nih.gov/pubmed/10882415", "http://www.ncbi.nlm.nih.gov/pubmed/2573519", "http://www.ncbi.nlm.nih.gov/pubmed/10761920" ], "ideal_answer": [ "Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, These two cell types are derived from common precursors in the thymus.", "no, CD8+ (cytotoxic) T cells, like CD4+ Helper T cells, are generated in the thymus not the thyroid and express the T-cell receptor.", "The CD4(+) helper versus CD8(+) cytotoxic T-cell fate decision serves as an excellent model to study binary fate decision processes. These two cell types are derived from common precursors in the thymus." ], "exact_answer": "no", "type": "yesno", "id": "5e2e1017fbd6abf43b000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "A fundamental question in developmental immunology is how bipotential thymocyte precursors generate both CD4+ helper and CD8+ cytotoxic T cell lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29677476", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 414, "text": "CD4+CD8+ progenitor thymocytes undergo selection following interaction with MHC class I and class II molecules bearing peptide self-antigens, giving rise to CD8+ cytotoxic and CD4+ helper or regulatory T cell lineages, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26301869", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 448, "text": "Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26301869", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 728, "text": ". The CD4(+) helper versus CD8(+) cytotoxic T-cell fate decision serves as an excellent model to study binary fate decision processes. These two cell types are derived from common precursors in the thymus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25591463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10761920", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 427, "text": "In the thymus, mature CD4+CD8- and CD4-CD8+ T cells expressing alpha beta T-cell antigen receptors (TCR) develop from immature thymocytes through CD4+CD8+ alpha beta TCR+ intermediates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1533274", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 559, "text": "In the thymus, immature CD8(-4)-TCR- cells differentiate, possibly via a short stage of CD8+4- thymocytes, into CD8+4+ TCR+ T cells and mature further into the main T cell populations, the CD8+4- TCR+ cytotoxic T lymphocytes and the CD4+8- TCR+ T helper cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2573519", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 264, "text": "In the mammalian thymus, CD4 helper T cells and CD8 cytotoxic T cells arise from a common precursor that expresses both CD4 and CD8.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7904067", "endSection": "abstract" } ] }, { "body": "What bacteria is associated with Gastric cancer and peptic ulcers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7886456", "http://www.ncbi.nlm.nih.gov/pubmed/29764950", "http://www.ncbi.nlm.nih.gov/pubmed/29432909", "http://www.ncbi.nlm.nih.gov/pubmed/15610081", "http://www.ncbi.nlm.nih.gov/pubmed/25539656", "http://www.ncbi.nlm.nih.gov/pubmed/16583309", "http://www.ncbi.nlm.nih.gov/pubmed/29446491", "http://www.ncbi.nlm.nih.gov/pubmed/8341988" ], "ideal_answer": [ "Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterial pathogen that colonizes the stomachs of more than half of all humans, is linked to chronic gastritis, peptic ulcers and gastric cancer.", "Peptic ulcer and gastric cancer are caused by the same bacteria, Helicobacter pylori." ], "exact_answer": [ "helicobacter pylori" ], "type": "factoid", "id": "5e3c6c9eb5b409ea53000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Helicobacter Pylori (H. pylori) is a gram-negative bacteria infecting numerous people all over the world. It has been established that H. pylori play an important role in pathogenesis of gastritis, peptic ulcer and gastric cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterial pathogen that colonizes the stomachs of more than half of all humans, is linked to chronic gastritis, peptic ulcers and gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Strains of Helicobacter pylori that cause ulcer or gastric cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29764950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "BACKGROUND Helicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25539656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Helicobacter pylori has been linked to chronic gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15610081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7886456", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 572, "text": "The pathogenesis of peptic ulcer and gastric cancer is closely associated with H. pylori gastritis and its subsequent atrophic sequelae (atrophic gastritis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8341988", "endSection": "abstract" } ] }, { "body": "Is Huntington's disease is caused by expansion of a CTG repeat in the HTT gene on Chromosome 4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28642124", "http://www.ncbi.nlm.nih.gov/pubmed/28986324", "http://www.ncbi.nlm.nih.gov/pubmed/17472569", "http://www.ncbi.nlm.nih.gov/pubmed/20668093", "http://www.ncbi.nlm.nih.gov/pubmed/30583877", "http://www.ncbi.nlm.nih.gov/pubmed/27400454", "http://www.ncbi.nlm.nih.gov/pubmed/30358836", "http://www.ncbi.nlm.nih.gov/pubmed/22383888", "http://www.ncbi.nlm.nih.gov/pubmed/21177255", "http://www.ncbi.nlm.nih.gov/pubmed/25656686", "http://www.ncbi.nlm.nih.gov/pubmed/31695145", "http://www.ncbi.nlm.nih.gov/pubmed/26079385", "http://www.ncbi.nlm.nih.gov/pubmed/25034271", "http://www.ncbi.nlm.nih.gov/pubmed/26642438", "http://www.ncbi.nlm.nih.gov/pubmed/28334749", "http://www.ncbi.nlm.nih.gov/pubmed/27721240", "http://www.ncbi.nlm.nih.gov/pubmed/29403030", "http://www.ncbi.nlm.nih.gov/pubmed/31529216", "http://www.ncbi.nlm.nih.gov/pubmed/23576953", "http://www.ncbi.nlm.nih.gov/pubmed/28497201", "http://www.ncbi.nlm.nih.gov/pubmed/29125980", "http://www.ncbi.nlm.nih.gov/pubmed/25035419", "http://www.ncbi.nlm.nih.gov/pubmed/23372043" ], "ideal_answer": [ "No, Huntington's disease is caused by expansion of a CAG repeat (not CTG) in the HTT gene on Chromosome 4.", "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT).", "Huntington disease (HD) is a dominantly inherited disorder caused by a CAG expansion mutation in the huntingtin (HTT) gene," ], "exact_answer": "no", "type": "yesno", "id": "5e31d181fbd6abf43b000053", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28986324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Huntington disease (HD) is a dominantly inherited disorder caused by a CAG expansion mutation in the huntingtin (HTT) gene, which results in the HTT protein that contains an expanded polyglutamine tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28497201", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "In Huntington's disease (HD), expansion of CAG codons in the huntingtin gene (HTT) leads to the aberrant formation of protein aggregates and the differential degeneration of striatal medium spiny neurons (MSNs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26079385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Huntington's disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27721240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "IMPORTANCE\n\nHuntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27400454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25035419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28642124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by an expanded CAG repeat in the HTT gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30358836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "IMPORTANCE Huntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27400454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Huntington 's disease ( HD ) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin ( HTT ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31695145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Huntington 's disease ( HD) , a dominantly inherited neurodegenerative disease , is defined by its genetic cause , a CAG-repeat expansion in the HTT gene , its motor and psychiatric symptomology and primary loss of striatal medium spiny neurons ( MSNs) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125980", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Huntington 's disease ( HD ) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin ( HTT ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23576953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Huntington 's disease ( HD ) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin ( HTT ) gene , which encodes a polyglutamine tract in the HTT protein . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26642438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Huntington 's disease ( HD ) is an autosomal progressive neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30583877", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Huntington 's disease ( HD ) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin ( htt ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17472569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Huntington 's disease ( HD) , caused by a CAG repeat expansion in the huntingtin ( HTT ) gene , is characterized by abnormal protein aggregates and motor and cognitive dysfunction . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Huntington 's disease ( HD ) is a neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin ( HTT ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20668093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Huntington 's disease ( HD ) is an autosomal disease caused by a CAG repeat expansion in the huntingtin ( HTT ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23372043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "BACKGROUND\nHuntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28642124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion in the trinucleotide CAG repeat in exon-1 in the huntingtin gene, located on chromosome 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31529216", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 437, "text": "HD is caused by expansion of the CAG trinucleotide repeat region in exon 1 of the Huntingtin gene (HTT), leading to the formation of mutant HTT transcripts (muHTT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary choreic movements, cognitive impairment, and behavioral changes, caused by the expansion of an unstable CAG repeat in HTT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25656686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Huntington disease (HD), the most common inherited cause of chorea, is an autosomal dominant disorder, caused by an expanded trinucleotide CAG repeat (>39) in the HTT gene on chromosome 4p16.3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25034271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by an expanded CAG repeat in the huntingtin (HTT) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30358836", "endSection": "abstract" } ] }, { "body": "What is the purpose of the 123 dihydrorhodamine assay?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23826567", "http://www.ncbi.nlm.nih.gov/pubmed/26865172", "http://www.ncbi.nlm.nih.gov/pubmed/19404956", "http://www.ncbi.nlm.nih.gov/pubmed/15331626", "http://www.ncbi.nlm.nih.gov/pubmed/25262961", "http://www.ncbi.nlm.nih.gov/pubmed/24890515", "http://www.ncbi.nlm.nih.gov/pubmed/19859718", "http://www.ncbi.nlm.nih.gov/pubmed/20856225" ], "ideal_answer": [ "detection of inheritance pattern in thirty-three mexican males with chronic granulomatous disease", "Dihydrorhodamine assays measure oxidative bursts and are used to quantify cell activation via respiratory bursts. Nitroblue-tetrazolium dye reduction test and 123 dihydro-rhodamine assay by flow cytometry are the screening tests for Chronic Granulomatous Disease.", "Dihydrorhodamine assay (DRB) is a simple, reliable, and valid method for studying oxidative stress, in particular oxidative stress and reactive oxygen species.", "We detected the female relatives within the families of male patients with CGD, and carried out the 123 dihydrorhodamine (DHR) assay in all female participants. Detection of inheritance pattern in thirty-three Mexican males with chronic granulomatous disease through 123 dihydrorhodamine assay." ], "exact_answer": [ "cell respiratory burst", "oxidative burst" ], "type": "factoid", "id": "5d387aa8a1e159510500000f", "snippets": [ { "offsetInBeginSection": 704, "offsetInEndSection": 822, "text": " detectable activation event and oxidative burst by the dihydrorhodamine assay, as a late, detectable activation event", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15331626", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1017, "text": "Neutrophil activation mediated by anti-PR3 antibodies was assessed by measuring the oxidative burst with a dihydrorhodamine assay", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19404956", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 639, "text": "The dihydrorhodamine (DHR) flow cytometry assay is a useful diagnostic tool for CGD that can detect absent or reduced NADPH oxidase activity in stimulated phagocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23826567", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 719, "text": "Intracellular reactive oxygen species were evaluated by dihydrorhodamine assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25262961", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1150, "text": "Nitroblue-tetrazolium dye reduction test and dihydro-rhodamine assay by flow cytometry are the screening tests for this disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865172", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 689, "text": "We detected the female relatives within the families of male patients with CGD, and carried out the 123 dihydrorhodamine (DHR) assay in all female participants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24890515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Detection of inheritance pattern in thirty-three Mexican males with chronic granulomatous disease through 123 dihydrorhodamine assay.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24890515", "endSection": "title" } ] }, { "body": "What is the mode of action of filgotinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30088677", "http://www.ncbi.nlm.nih.gov/pubmed/30360969", "http://www.ncbi.nlm.nih.gov/pubmed/27993829", "http://www.ncbi.nlm.nih.gov/pubmed/27993828", "http://www.ncbi.nlm.nih.gov/pubmed/28622463", "http://www.ncbi.nlm.nih.gov/pubmed/30360970", "http://www.ncbi.nlm.nih.gov/pubmed/27988142", "http://www.ncbi.nlm.nih.gov/pubmed/25681059", "http://www.ncbi.nlm.nih.gov/pubmed/28838249", "http://www.ncbi.nlm.nih.gov/pubmed/29566740", "http://www.ncbi.nlm.nih.gov/pubmed/26693854" ], "ideal_answer": [ "Filgotinib is an oral selective Janus kinase 1 (JAK1) inhibitor. It has been tested in patients with rheumatoid arthritis and Chroni's disease, and has been shown to be effective.", "Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1) currently in development for the treatment of rheumatoid arthritis and Crohn's disease.", "Filgotinib is an oral selective JAK inhibitor. It works by inhibiting JAK1.", "Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1).", "Filgotinib (GS-6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthritis and with Crohn's disease. Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes.", "Filgotinib is an oral selective JAK1 inhibitor. It has been tested in patients with rheumatoid arthritis and Chroni's disease, and has been shown to be safe and efficacious.", "Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor,", "Selective inhibition of JAK-1 with filgotinib shows initial efficacy in RA with an encouraging safety profile in these exploratory studies. The selectivity of filgotinib for JAK1 may have theoretical advantages in terms of limiting toxicity." ], "exact_answer": [ "JAK1 inhibitor" ], "type": "factoid", "id": "5cd96f33a49efeb44c000004", "snippets": [ { "offsetInBeginSection": 27, "offsetInEndSection": 187, "text": "Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1) currently in development for the treatment of rheumatoid arthritis and Crohn's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25681059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Clinical Confirmation that the Selective JAK1 Inhibitor Filgotinib (GLPG0634) has a Low Liability for Drug-drug Interactions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26693854", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 284, "text": "The selective Janus kinase 1 inhibitor filgotinib (GLPG0634), which is currently in clinical development for the treatment of rheumatoid arthritis (RA) and Crohn's disease, demonstrated encouraging safety and efficacy profiles in RA patients after 4 weeks of daily dosing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26693854", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1577, "text": " In vitro, filgotinib and its active metabolite at clinically relevant concentrations did not interact with cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases, and did not inhibit key drug transporters. In the clinic, a lack of relevant pharmacokinetic drug interactions by filgotinib and its active metabolite with substrates of CYP3A4, as well as with organic anion transporters involved in methotrexate elimination were found.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26693854", "endSection": "abstract" }, { "offsetInBeginSection": 1903, "offsetInEndSection": 2042, "text": "Selective inhibition of JAK-1 with filgotinib shows initial efficacy in RA with an encouraging safety profile in these exploratory studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28622463", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 690, "text": "Here we review the pharmacology and clinical trial data for efficacy and safety of filgotinib, an investigational selective JAK1 inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28838249", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 909, "text": "The selectivity of filgotinib for JAK1 may have theoretical advantages in terms of limiting toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28838249", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 123, "text": "Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27988142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993829", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 127, "text": "To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993828", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 235, "text": "To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993828", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 378, "text": "The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360970", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 241, "text": "We aimed to investigate the efficacy and safety of filgotinib, a selective JAK1 inhibitor, for the treatment of psoriatic arthritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360969", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Influence of age and renal impairment on the steady state pharmacokinetics of filgotinib, a selective JAK1 inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30088677", "endSection": "title" }, { "offsetInBeginSection": 6, "offsetInEndSection": 214, "text": "Filgotinib (GS-6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthritis and with Crohn's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30088677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566740", "endSection": "title" } ] }, { "body": "Is Huntington's disease caused by a dominate or recessive gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29413175", "http://www.ncbi.nlm.nih.gov/pubmed/31286142", "http://www.ncbi.nlm.nih.gov/pubmed/2881213", "http://www.ncbi.nlm.nih.gov/pubmed/22119622", "http://www.ncbi.nlm.nih.gov/pubmed/25356969", "http://www.ncbi.nlm.nih.gov/pubmed/14526190", "http://www.ncbi.nlm.nih.gov/pubmed/15764008", "http://www.ncbi.nlm.nih.gov/pubmed/28927719", "http://www.ncbi.nlm.nih.gov/pubmed/29134321", "http://www.ncbi.nlm.nih.gov/pubmed/11723754" ], "ideal_answer": [ "Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease", "Huntington's disease is caused by an autosomal dominant gene.", "Huntington's disease (HD) is an inherited NDD caused by autosomal-dominant expanded CAG trinucleotide repeat mutation in the gene coding for Huntingtin (Htt)." ], "exact_answer": [ "dominant" ], "type": "factoid", "id": "5e31cbd4fbd6abf43b00004f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease characterized by gradual deterioration of motor and cognitive functions and development of psychiatric deficits. Animal models provide powerful means to study the pathological", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28927719", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 356, "text": "Huntington's disease (HD) is an inherited NDD caused by autosomal-dominant expanded CAG trinucleotide repeat mutation in the gene coding for Huntingtin (Htt). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29134321", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 346, "text": " Huntington's disease (HD) is an autosomal-dominant, progressive neurodegenerative disease characterized by movement disorder, psychiatric symptoms and cognitive decline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413175", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1264, "text": "The D4S10 locus, defined by the probe G8 and linked to the gene for Huntington's disease (HD), has permitted us to identify individuals with a high probability of being homozygous for this autosomal dominant neurodegenerative disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2881213", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 644, "text": "Huntington's disease is a fatal autosomal dominant neurodegenerative disease caused by an abnormal CAG expansion in huntingtin's gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31286142", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 643, "text": "Huntington's disease is a fatal autosomal dominant neurodegenerative disease caused by an abnormal CAG expansion in huntingtin's gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31286142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Huntington's disease is an autosomal dominant neurodegenerative disease caused by a toxic gain of function mutation in the huntingtin gene (Htt)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22119622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Huntington's disease (HD) is a late onset, incurable, autosomal dominantly-inherited, progressive neuropsychiatric disease, characterised by chorea, changes in personality, mood and behaviour, and dementia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11723754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Huntington's disease (HD) is a genetically dominant neurodegenerative condition caused by an unique mutation in the disease gene huntingtin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14526190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Huntington disease is an autosomal-dominant neurodegenerative disease of mid-life onset caused by expansion of a polymorphic trinucleotide (CAG) repeat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25356969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Huntington disease (HD) is a well-defined autosomal dominant neurodegenerative disease caused by CAG repeat expansions in HD gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15764008", "endSection": "abstract" } ] }, { "body": "What is RiboTag profiling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26054767" ], "ideal_answer": [ "RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures.", "Ribo tag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell types and organisms. It is a simple, sensitive, rapid and relatively cheap method for integrative epigenomic profiling. The method can be used to identify endogenous and ectopically expressed ribosomal RNAs (RP), which are then analyzed using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of ubiquitously expressed proteins.", "RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures. RiboTag immunoprecipitation is capable of recovering high integrity RNA from small numbers of transfected cells that can then be interrogated by a variety of methods (e.g., RT-qPCR, PCR array, RNA-Seq) and compared with basal RNA expression of the entire culture. Co-transfection of RiboTag with small hairpin RNA (shRNA) constructs can validate and accurately assess the degree of gene expression knockdown." ], "type": "summary", "id": "5e4700e03f54159529000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26054767", "endSection": "title" }, { "offsetInBeginSection": 235, "offsetInEndSection": 1511, "text": "Here we describe our adaptation of a ribosomal capture strategy that was designed to be used in transgenic mice expressing tagged ribosomal subunits (RiboTag) in specific cell types, thereby allowing measurement of translating RNAs from desired cell types within complex tissues. Using this strategy we were able to isolate and analyze neuron-specific RNA despite the presence of glia by co-transfecting experimental plasmids with plasmids that selectively express RiboTag in neurons. RiboTag immunoprecipitation was capable of recovering high integrity RNA from small numbers of transfected cells that can then be interrogated by a variety of methods (e.g., RT-qPCR, PCR array, RNA-Seq) and compared with basal RNA expression of the entire culture. Additionally, we demonstrate how co-transfection of RiboTag with small hairpin RNA (shRNA) constructs can validate and accurately assess the degree of gene expression knockdown, and how RiboTag can be used to measure receptor-mediated gene regulation with transiently expressed designer receptors exclusively activated by designer drugs (DREADDs). RiboTag co-transfection represents a convenient and powerful tool to isolate RNA from a specific subset of cultured cells with a variety of applications for experiments in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26054767", "endSection": "abstract" } ] }, { "body": "Is there an increased risk of meningiomas in atomic bomb survivors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12381708", "http://www.ncbi.nlm.nih.gov/pubmed/8707402", "http://www.ncbi.nlm.nih.gov/pubmed/10408177", "http://www.ncbi.nlm.nih.gov/pubmed/15378499" ], "ideal_answer": [ "Yes, the incidence of meningiomas is increased in atomic bomb survivors." ], "exact_answer": "yes", "type": "yesno", "id": "5e323780fbd6abf43b000055", "snippets": [ { "offsetInBeginSection": 869, "offsetInEndSection": 1018, "text": "RESULTS: Meningioma was the most common tumor among clinically diagnosed tumors, followed by neuroepithelial tumor, schwannoma, and pituitary tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15378499", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1659, "text": "The predominance of meningiomas over neuroepithelial tumors in the Japanese population was noteworthy and warrants further investigation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15378499", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1427, "text": "Risk increases, although not statistically significant, were seen for meningiomas (ERR(Sv) = 0.6, 95% CI = -0.01 to 1.8), gliomas (ERR(Sv) = 0.6, 95% CI = -0.2 to 2.0), other nervous system tumors (ERR(Sv) = 0.5, 95% CI = <-0.2 to 2.2), and pituitary tumors (ERR(Sv) = 1.0, 95% CI = <-0.2 to 3.5).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12381708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "High incidence of meningioma among Hiroshima atomic bomb survivors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408177", "endSection": "title" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1409, "text": "The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Incidence of intracranial meningiomas in Nagasaki atomic-bomb survivors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8707402", "endSection": "title" }, { "offsetInBeginSection": 583, "offsetInEndSection": 936, "text": "The analysis showed a high correlation between incidence of meningiomas and distance from the hypocenter. The incidence among Nagasaki atomic-bomb survivors over 40 years of age, especially in those proximally exposed, appears to be increasing, in inverse proportion to the exposure distance, since 1981, 36 years after the explosion of the atomic bomb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8707402", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1196, "text": "The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408177", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1409, "text": "The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408177", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 798, "text": "The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10408177", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 688, "text": "The analysis showed a high correlation between incidence of meningiomas and distance from the hypocenter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8707402", "endSection": "abstract" } ] }, { "body": "What is foliglurax?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30216534" ], "ideal_answer": [ "Foliglurax is a positive allosteric modulator of the metabotropic glutamate receptor 4. Foliglurax induced a robust and dose-dependent reversal of parkinsonian motor symptoms in macaques, including bradykinesia, tremor, posture, and mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having therapeutic efficacy on both parkinsonian motor impairment and l-dopa-induced dyskinesia. It was the first compound of its class to enter phase IIa clinical trials." ], "type": "summary", "id": "5e2db427fbd6abf43b000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "An mGlu4-Positive Allosteric Modulator Alleviates Parkinsonism in Primates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30216534", "endSection": "title" }, { "offsetInBeginSection": 405, "offsetInEndSection": 572, "text": "We studied whether a novel positive allosteric modulator of the metabotropic glutamate receptor 4, PXT002331 (foliglurax), could reduce parkinsonism in primate models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30216534", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 1182, "text": "As an adjunct to l-dopa, PXT002331 induced a robust and dose-dependent reversal of parkinsonian motor symptoms in macaques, including bradykinesia, tremor, posture, and mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having therapeutic efficacy on both parkinsonian motor impairment and l-dopa-induced dyskinesia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30216534", "endSection": "abstract" }, { "offsetInBeginSection": 1574, "offsetInEndSection": 1655, "text": "PXT002331 is the first compound of its class to enter phase IIa clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30216534", "endSection": "abstract" } ] }, { "body": "What is the genetic basis for Cornelia de Lange's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24038889" ], "ideal_answer": [ "Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified.", "Approximately 60% of Cornelia de Lange Syndrome (CdLS) cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3. Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified.", "Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified. 60% of CdLS cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3." ], "exact_answer": [ "Mutations in genes that are associated with cohesin" ], "type": "factoid", "id": "5cebeb82a49efeb44c000009", "snippets": [ { "offsetInBeginSection": 372, "offsetInEndSection": 510, "text": "Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038889", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 674, "text": "60% of CdLS cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038889", "endSection": "abstract" } ] }, { "body": "Are gut microbiota profiles altered by irradiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30343431", "http://www.ncbi.nlm.nih.gov/pubmed/30430918", "http://www.ncbi.nlm.nih.gov/pubmed/30459840" ], "ideal_answer": [ "Yes, \tIrradiation profoundly impacted gut microbiota profiles" ], "exact_answer": "yes", "type": "yesno", "id": "5e48e0e0f8b2df0d49000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Specific Members of the Gut Microbiota are Reliable Biomarkers of Irradiation Intensity and Lethality in Large Animal Models of Human Health.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30430918", "endSection": "title" }, { "offsetInBeginSection": 887, "offsetInEndSection": 959, "text": "Irradiation profoundly impacted gut microbiota profiles in both animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30343431", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1604, "text": "Our findings suggest that gut symbiont-based probiotics can be used as agents for reversing radiation-induced ecological fitness decrease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30459840", "endSection": "abstract" } ] }, { "body": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27699239", "http://www.ncbi.nlm.nih.gov/pubmed/29440769", "http://www.ncbi.nlm.nih.gov/pubmed/27283895", "http://www.ncbi.nlm.nih.gov/pubmed/29721382", "http://www.ncbi.nlm.nih.gov/pubmed/26851185", "http://www.ncbi.nlm.nih.gov/pubmed/27846884" ], "ideal_answer": [ "Yes. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation.", "Yes, TIM-3 has shown promising results in early phases of trials in NSCLC patients and can be a target for cancer immunotherapy.", "Yes, TIM-3 has emerged as an important target of cancer immunotherapy because of its preferential expression in NSCLC cell lines and its presence in 90% of tumors. (PMID: 21494614) We have developed a cancer vaccine in whichtim-3 is fused with dendritic cells resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. This (CT)n element has been shown to induce poly(ADP-ribose) polymerase activation, and it has also been suggested thatTim-3 may act as a tumor suppressor gene, thus making it a potential therapeutic target of CDKN2A/PD-", " Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation.", "Implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.", " Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients. Cytometric profiling identified an immunologically \"hot\" cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically \"cold\" cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers" ], "exact_answer": "yes", "type": "yesno", "id": "5c7a4c35d774d04240000007", "snippets": [ { "offsetInBeginSection": 1539, "offsetInEndSection": 1749, "text": " Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27283895", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1177, "text": "Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27283895", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 488, "text": "In present study, we detected the dynamic expression of eight major checkpoint molecules (CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA) on CIK cells from NSCLC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27283895", "endSection": "abstract" }, { "offsetInBeginSection": 2689, "offsetInEndSection": 2906, "text": "Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors on T cells and other approaches such as adoptive cell transfer are tested for clinical efficacy in melanoma as well.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27846884", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1483, "text": "We found immune activation coexistent with elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA, and CTLA-4, along with increases in tumor infiltration by CD4(+)Foxp3(+) regulatory T cells in lung adenocarcinomas that displayed an EMT phenotype", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26851185", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 853, "text": "Cytometric profiling identified an immunologically \"hot\" cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically \"cold\" cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27699239", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1249, "text": " Interestingly, CD161+ CD4+ T cells highly express OX40 co-stimulatory receptor, less frequently 4-1BB, and display an activated but not completely exhausted PD-1-positive Tim-3-negative phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29721382", "endSection": "abstract" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1046, "text": ". Furthermore, overexpression of targetable immune checkpoints, such as CTLA-4 and TIM-3 were associated with EMT in both NSCLCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29440769", "endSection": "abstract" } ] }, { "body": "How does LB-100 affect the DDR proteins (BRCA1, Chk2, and \u03b3H2AX)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25376608" ], "ideal_answer": [ "LB100 induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and gH2AX)." ], "exact_answer": [ "Hyperphosphorylation", "Hyperphosphorylates" ], "type": "factoid", "id": "5e29fb27aa19d74431000005", "snippets": [ { "offsetInBeginSection": 1141, "offsetInEndSection": 1347, "text": "LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and \u03b3H2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376608", "endSection": "abstract" } ] }, { "body": "What particles is Hadron therapy using?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29609813", "http://www.ncbi.nlm.nih.gov/pubmed/28884707", "http://www.ncbi.nlm.nih.gov/pubmed/29625810" ], "ideal_answer": [ "Hadron therapy is using proton beams." ], "exact_answer": [ "Proton beams" ], "type": "factoid", "id": "5e48edb1f8b2df0d49000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The use of hadron beams, especially proton beams, in cancer radiotherapy has expanded rapidly in the past two decades. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884707", "endSection": "abstract" } ] }, { "body": "Does an interferon (IFN) signature exist for SLE patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29850618", "http://www.ncbi.nlm.nih.gov/pubmed/21576205", "http://www.ncbi.nlm.nih.gov/pubmed/29321042", "http://www.ncbi.nlm.nih.gov/pubmed/28830352" ], "ideal_answer": [ "Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. An IFN-I score (positive or negative), as a measure of IFN-I activation, is assessed using the expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)." ], "exact_answer": "yes", "type": "yesno", "id": "5c7019557c78d6947100005f", "snippets": [ { "offsetInBeginSection": 69, "offsetInEndSection": 167, "text": "Interferon regulatory factor 7 activation correlates with the IFN signature and recurrent disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576205", "endSection": "title" }, { "offsetInBeginSection": 801, "offsetInEndSection": 941, "text": "In SLE post-transplant, recurrent disease activity and induction of IRF7 protein expression correlated with activation of the IFN signature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21576205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature gene downregulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28830352", "endSection": "title" }, { "offsetInBeginSection": 1068, "offsetInEndSection": 1329, "text": "We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4+ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3+ T cells from human patients following immunosuppressant therapy including steroid, respectively", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28830352", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 992, "text": "We found that cDCs from prediseased TCSle male mice express the IFN signature as female TCSle cDCs do. Estrogens are necessary but not sufficient to express this IFN signature, but high doses of E2 can compensate for other steroidal components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Conventional DCs from Male and Female Lupus-Prone B6.NZM Sle1/Sle2/Sle3 Mice Express an IFN Signature and Have a Higher Immunometabolism That Are Enhanced by Estrogen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29850618", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Type I IFN signature in childhood-onset systemic lupus erythematosus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321042", "endSection": "title" }, { "offsetInBeginSection": 114, "offsetInEndSection": 190, "text": " Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321042", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 677, "text": "The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29321042", "endSection": "abstract" } ] }, { "body": "Is AND-1/Ctf4 essential for proliferation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30082684" ], "ideal_answer": [ "Yes. AND-1 fork protection function prevents fork resection and is essential for proliferation.", "Yes. AND-1/Ctf4 bridges the CMG helicase and DNA polymerase alpha, facilitating replication. AND-1 depletion is incompatible with proliferation, owing to cells accumulating in G2 with activated DNA damage checkpoint. Replication without AND-1 causes fork speed slow-down and accumulation of long single-stranded DNA (ssDNA) gaps at the replication fork junction, with these regions being converted to DNA double strand breaks (DSBs) in G2." ], "exact_answer": "yes", "type": "yesno", "id": "5e36d924b5b409ea5300000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "AND-1 fork protection function prevents fork resection and is essential for proliferation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30082684", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1036, "text": "AND-1/Ctf4 bridges the CMG helicase and DNA polymerase alpha, facilitating replication. Using an inducible degron system in avian cells, we find that AND-1 depletion is incompatible with proliferation, owing to cells accumulating in G2 with activated DNA damage checkpoint. Replication without AND-1 causes fork speed slow-down and accumulation of long single-stranded DNA (ssDNA) gaps at the replication fork junction, with these regions being converted to DNA double strand breaks (DSBs) in G2. Strikingly, resected forks and DNA damage accumulation in G2, but not fork slow-down, are reverted by treatment with mirin, an MRE11 nuclease inhibitor. Domain analysis of AND-1 further revealed that the HMG box is important for fast replication but not for proliferation, whereas conversely, the WD40 domain prevents fork resection and subsequent DSB-associated lethality. Thus, our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30082684", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1055, "text": "Thus , our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30082684", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1037, "text": "Thus, our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30082684", "endSection": "abstract" } ] }, { "body": "Does the BRAFV600E mutation have an effect on clinical response to radioiodine therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26780618", "http://www.ncbi.nlm.nih.gov/pubmed/29549631", "http://www.ncbi.nlm.nih.gov/pubmed/30312216", "http://www.ncbi.nlm.nih.gov/pubmed/26838744" ], "ideal_answer": [ "Yes, it has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis." ], "exact_answer": "yes", "type": "yesno", "id": "5e4adcbe6d0a277941000017", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "Preclinical studies showed that BRAF mutation significantly reduced radioiodine uptake and decreased the sensitivity to radioactive iodine (RAI) therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312216", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1667, "text": "The status of BRAF mutation may not affect the clinical response to RAI therapy for patients with PTMC with intermediate-risk to high-risk features. More trials examining the role of BRAF mutation in guiding postoperative RAI therapy are needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312216", "endSection": "abstract" }, { "offsetInBeginSection": 1523, "offsetInEndSection": 1786, "text": "our results suggest that the combination of BRAFV600E+ve mutation and MIBI-ve scintigraphy may be considered a negative prognostic clue, which predicts the absence of radioiodine uptake at pT-WBS in DTC patients with incomplete bio-chemical response to first RAIT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29549631", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1616, "text": "The results indicate that BRAF(V600E) mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26838744", "endSection": "abstract" } ] }, { "body": "Which phosphatase is inhibited by LB-100?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29199006" ], "ideal_answer": [ "LB-100 is a phosphatase 2A inhibitor" ], "exact_answer": [ "Protein phosphatase 2A" ], "type": "factoid", "id": "5e29f666aa19d74431000001", "snippets": [ { "offsetInBeginSection": 402, "offsetInEndSection": 524, "text": "Here, we examined radiosensitizing effects of LB-100, a novel inhibitor of PP2A against AAM as a novel treatment strategy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "LB-100, a novel Protein Phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199006", "endSection": "title" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1094, "text": "Pharmacologic PP2A inhibition with LB-100 prior to RT enhanced the radiosensitivity of meningioma cells and reduced survival fraction in clonogenic assays. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29199006", "endSection": "abstract" } ] }, { "body": "What are the most common side effects of amantadine ER?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29564954" ], "ideal_answer": [ "The most common side effects of amantadine ER are hallucination, dizziness, orthostatic hypotension and pedal edema." ], "exact_answer": [ [ "Hallucination" ], [ "Dissiness" ], [ "Orthostatic hypotension" ], [ "Pedal edema" ] ], "type": "list", "id": "5e2dadcffbd6abf43b000011", "snippets": [ { "offsetInBeginSection": 590, "offsetInEndSection": 690, "text": "The most common side effects are hallucination, dizziness, orthostatic hypotension and pedal edema. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29564954", "endSection": "abstract" } ] }, { "body": "Which symptoms comprise Abdominal aortic aneurysm rupture Triad?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25687811", "http://www.ncbi.nlm.nih.gov/pubmed/21097454", "http://www.ncbi.nlm.nih.gov/pubmed/25003065", "http://www.ncbi.nlm.nih.gov/pubmed/19520879", "http://www.ncbi.nlm.nih.gov/pubmed/24964430", "http://www.ncbi.nlm.nih.gov/pubmed/3782278" ], "ideal_answer": [ "Classic triad of Abdominal aortic aneurysm rupture include shock, acute abdominal pain, and pulsatile abdominal mass." ], "exact_answer": [ [ "shock" ], [ "acute abdominal pain" ], [ "pulsatile abdominal mass" ] ], "type": "list", "id": "5e2f93bbfbd6abf43b00002e", "snippets": [ { "offsetInBeginSection": 697, "offsetInEndSection": 859, "text": "RESULTS: The correct diagnosis based on the classic triad of shock, acute abdominal pain, and pulsatile abdominal mass was made in only one of 19 (5.3%) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25687811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Only 50% of abdominal aortic aneurysms present with the classic triad of hypotension, back pain and a pulsatile abdominal mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24964430", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 223, "text": "Some of these patients present with the classic triad of symptoms such as abdominal pain, pulsatile abdominal mass and shock. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003065", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 768, "text": "The clinical onset was characterized by the unique syndrome: continuous abdominal bruit, abdominal and left flank pain with an associated pulsatile mass (Mansour Triad).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097454", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 258, "text": "Most AAAs rupture into the retroperitoneal cavity, which results in the classical triad of pain, hypotension, and a pulsatile mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19520879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Rupture of an abdominal aortic aneurysm is readily diagnosed when the triad of abdominal or back pain, shock and a pulsatile abdominal mass are present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3782278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Rupture of an abdominal aortic aneurysm is readily diagnosed when the triad of abdominal or back pain , shock and a pulsatile abdominal mass are present", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3782278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Rupture of an abdominal aortic aneurysm is readily diagnosed when the triad of abdominal or back pain, shock and a pulsatile abdominal mass are present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3782278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Only 50% of abdominal aortic aneurysms present with the classic triad of hypotension, back pain and a pulsatile abdominal mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24964430", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 222, "text": "Some of these patients present with the classic triad of symptoms such as abdominal pain, pulsatile abdominal mass and shock.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003065", "endSection": "abstract" } ] }, { "body": "List symptoms of Allgrove syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20051279", "http://www.ncbi.nlm.nih.gov/pubmed/16937455", "http://www.ncbi.nlm.nih.gov/pubmed/12752575", "http://www.ncbi.nlm.nih.gov/pubmed/29237697", "http://www.ncbi.nlm.nih.gov/pubmed/17880814", "http://www.ncbi.nlm.nih.gov/pubmed/20200814", "http://www.ncbi.nlm.nih.gov/pubmed/30501443", "http://www.ncbi.nlm.nih.gov/pubmed/17880786", "http://www.ncbi.nlm.nih.gov/pubmed/12497758", "http://www.ncbi.nlm.nih.gov/pubmed/27555148", "http://www.ncbi.nlm.nih.gov/pubmed/29383495", "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "http://www.ncbi.nlm.nih.gov/pubmed/29874194", "http://www.ncbi.nlm.nih.gov/pubmed/29866068", "http://www.ncbi.nlm.nih.gov/pubmed/16938764", "http://www.ncbi.nlm.nih.gov/pubmed/29255950", "http://www.ncbi.nlm.nih.gov/pubmed/29492088", "http://www.ncbi.nlm.nih.gov/pubmed/27698338", "http://www.ncbi.nlm.nih.gov/pubmed/23056690", "http://www.ncbi.nlm.nih.gov/pubmed/21073617", "http://www.ncbi.nlm.nih.gov/pubmed/29334914", "http://www.ncbi.nlm.nih.gov/pubmed/16197535" ], "ideal_answer": [ "The classical clinical triad of the Allgrove syndrome includes alacrima, achalasia and adrenal insufficiency. It can be also associated with progressive peripheral neuropathy." ], "exact_answer": [ [ "alacrima" ], [ "achalasia" ], [ "adrenal insufficiency" ] ], "type": "list", "id": "5e2f9596fbd6abf43b00002f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "OBJECTIVE: Triple-A or Allgrove syndrome is an autosomal recessive disorder due to mutations in the AAAS gene, which encodes a nucleoporin named ALADIN. It is characterized by a classical clinical triad: alacrima, achalasia and adrenal insufficiency, the canonic symptoms that are associated with progressive peripheral neuropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29237697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Triple A syndrome (TAS) or Allgrove syndrome (OMIM #231550) is a rare autosomal recessive disorder characterised by adrenocorticotropic hormone-resistant adrenal insufficiency, alacrima, achalasia, and neurological and dermatological abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "BACKGROUND: Triple A syndrome (or Allgrove syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency and autonomic/neurological abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29334914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Allgrove syndrome, also known as Triple A syndrome, is a rare autosomal recessive genetic disease characterized by three signs: esophageal achalasia, adrenocorticotropic hormone refractoriness, and alacrima. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29383495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Background Triple A syndrome is characterized by achalasia, alacrima and adrenal insufficiency with neurological manifestations occurring later in the course of the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29874194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BACKGROUND: Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of achalasia, alacrimia and adrenal insufficiency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29866068", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 332, "text": "Allgrove syndrome is caused by homozygous and/or compound heterozygous mutations on Chromosome 12q13, designated as \"AAA\" (Achalasia, Addisonianism Alacrima).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30501443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The triple A or Allgrove 's syndrome is an autosomal recessive disorder characterized by the triad of achalasia cardia , alacrima and ACTH resistant adrenocortical insufficiency . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16937455", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 905, "text": "Allgrove 's syndrome , is considered to be a separate condition , characterized by glucocorticoid deficiency along with alacrimia , achalasia and neurological deficits . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17880814", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 713, "text": "The majority of authors attribute a limited contribution unless achalasia is related to a multisystem disorder , like the triple-A or Allgrove 's syndrome , an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone ( ACTH ) resistant adrenal insufficiency , achalasia and alacrima . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16197535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Triple A syndrome , also known as Allgrove syndrome , is a rare autosomal recessive disorder characterized by three cardinal symptoms: adrenal insufficiency due to ACTH insensitivity , achalasia and alacrima . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20200814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Triple A ( Allgrove ) syndrome , an autosomal recessive disease is characterized by achalasia , alacrimia and ACTH-resistant adrenal failure with progressive neurological syndrome including central , peripheral and autonomic nervous system impairment , and mild mental retardation . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29492088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Allgrove ( Triple A ) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone ( ACTH ) resistance , achalasia , and alacrimia . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 571, "text": "Various syndromes include achalasia in their symptomatology , such as the triple A syndrome or Allgrove syndrome ( Addisonianism , achalasia , and alacrimia) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The triple A or Allgrove syndrome is an autosomal-recessive disease ( MIM*231550 ) characterized by the triad of achalasia , alacrima and adrenocorticotropic hormone ( ACTH)-resistant adrenal insufficiency . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12752575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Triple A syndrome ( TAS ) or Allgrove syndrome ( OMIM #231550 ) is a rare autosomal recessive disorder characterised by adrenocorticotropic hormone-resistant adrenal insufficiency , alacrima , achalasia , and neurological and dermatological abnormalities . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "BACKGROUND\nAllgrove syndrome is a multisystem disorder first described in 1978 and is classically associated with esophageal achalasia, alacrima, and adrenal insufficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30501443", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 571, "text": "Here we report an 18-year-old boy diagnosed as having Allgrove syndrome, with ACTH resistant adrenal insufficiency, achalasia, alacrimia, and severe motor polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Allgrove (Triple A) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrimia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26354489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Allgrove syndrome is a rare autosomal recessive condition characterized by adrenal insufficiency, achalasia, alacrima and occasionally autonomic disturbances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23056690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "UNLABELLED: Allgrove syndrome (or triple-A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency (glucocorticoid in the majority of cases) and autonomic/neurological abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16938764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "INTRODUCTION: Allgrove syndrome (AS) is a rare autosomal recessive disorder characterized by achalasia cardia, alacrimia, and adrenocorticotropic hormone-resistant adrenal insufficiency which is sometimes associated with autonomic dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27555148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and autonomic/neurological abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20051279", "endSection": "abstract" }, { "offsetInBeginSection": 704, "offsetInEndSection": 879, "text": "Allgrove syndrome should be suspected in patients with neurological impairment associated with two or more of the main symptoms (alacrima, achalasia or adrenal insufficiency).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20051279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Allgrove syndrome (triple A syndrome) is an autosomal recessive disorder characterised by adrenocortical insufficiency, achalasia and alacrima.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12497758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "Patient: Female, 6 Final Diagnosis: Allgrove syndrome Symptoms: Achalasia adrenal insufficiency alacrima Medication: : Clinical Procedure: : Specialty: Pediatrics and Neonatology Objective: Rare disease Background: Allgrove syndrome, or triple \"A\" syndrome (3A syndrome), is a rare autosomal recessive syndrome with variable phenotype, and an estimated prevalence of 1 per 1,000,000 individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27698338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "OBJECTIVE: Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima and many cases have multi-systems disorder: endocrine, gastrointestinal tract, eyes and nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17880786", "endSection": "abstract" } ] }, { "body": "What is water radiolysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28376128", "http://www.ncbi.nlm.nih.gov/pubmed/29734786", "http://www.ncbi.nlm.nih.gov/pubmed/29337289" ], "ideal_answer": [ "Water radiolysis involves chemical decomposition of the water molecule into free radicals after exposure to ionizing radiation. These free radicals have deleterious effects on normal cell physiology." ], "type": "summary", "id": "5e482f08d14c9f295d00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Water radiolysis involves chemical decomposition of the water molecule into free radicals after exposure to ionizing radiation. These free radicals have deleterious effects on normal cell physiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29337289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Electron Nuclear Dynamics Simulations of Proton Cancer Therapy Reactions: Water Radiolysis ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29734786", "endSection": "title" }, { "offsetInBeginSection": 227, "offsetInEndSection": 351, "text": " simulate water radiolysis reactions-i.e. the PCT processes that generate the DNA-damaging species against cancerous cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28376128", "endSection": "abstract" } ] }, { "body": "How do the plasma concentrations of amantadine extended release and amantadine immediate release compare?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29564954", "http://www.ncbi.nlm.nih.gov/pubmed/29777529" ], "ideal_answer": [ "When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release.", "When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release. PK modeling suggested the recommended daily ADS-5102 dosage (274 mg qhs) resulted in 1.4- to 2.0-fold higher amantadine plasma concentrations during the day versus amantadine IR." ], "type": "summary", "id": "5e2dae57fbd6abf43b000012", "snippets": [ { "offsetInBeginSection": 308, "offsetInEndSection": 440, "text": "When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29564954", "endSection": "abstract" }, { "offsetInBeginSection": 1402, "offsetInEndSection": 1580, "text": "PK modeling suggested the recommended daily ADS-5102 dosage (274\u00a0mg qhs) resulted in 1.4- to 2.0-fold higher amantadine plasma concentrations during the day versus amantadine IR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29777529", "endSection": "abstract" } ] }, { "body": "Is the BAGEL algorithm used for arrayed CRISPR screens?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27083490" ], "ideal_answer": [ "No. BAGEL (Bayesian Analysis of Gene EssentiaLity) is a supervised learning method for analyzing pooled library gene knockout screens. It offers significantly greater sensitivity than current methods, while computational optimizations reduce runtime by an order of magnitude." ], "exact_answer": "no", "type": "yesno", "id": "5e30b56efbd6abf43b000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "BAGEL: a computational framework for identifying essential genes from pooled library screens.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083490", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 923, "text": "The adaptation of the CRISPR-Cas9 system to pooled library gene knockout screens in mammalian cells represents a major technological leap over RNA interference, the prior state of the art. New methods for analyzing the data and evaluating results are needed.RESULTS: We offer BAGEL (Bayesian Analysis of Gene EssentiaLity), a supervised learning method for analyzing gene knockout screens. Coupled with gold-standard reference sets of essential and nonessential genes, BAGEL offers significantly greater sensitivity than current methods, while computational optimizations reduce runtime by an order of magnitude.CONCLUSIONS: Using BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms. BAGEL shows high sensitivity and specificity even across screens performed by different labs using different libraries and reagents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083490", "endSection": "abstract" }, { "offsetInBeginSection": 628, "offsetInEndSection": 794, "text": "CONCLUSIONS\n\nUsing BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "BAGEL: a computational framework for identifying essential genes from pooled library screens", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083490", "endSection": "title" }, { "offsetInBeginSection": 628, "offsetInEndSection": 794, "text": "CONCLUSIONS\nUsing BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083490", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 790, "text": "CONCLUSIONS: Using BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083490", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 789, "text": "Conclusions Using BAGEL, we identify ~2000 fitness genes in pooled library knockout screens in human cell lines at 5 % FDR, a major advance over competing platforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27083490", "endSection": "abstract" } ] }, { "body": "What is included in the LACE Index?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30279159", "http://www.ncbi.nlm.nih.gov/pubmed/30040677", "http://www.ncbi.nlm.nih.gov/pubmed/29343987", "http://www.ncbi.nlm.nih.gov/pubmed/23696773", "http://www.ncbi.nlm.nih.gov/pubmed/30926557", "http://www.ncbi.nlm.nih.gov/pubmed/29634597", "http://www.ncbi.nlm.nih.gov/pubmed/29148921" ], "ideal_answer": [ "The LACE index is a simple tool that includes 4 parameters: Length of stay, Acuity of admission, Comorbidity, and Emergency visits in the previous 6 months. It is used to predict early re-admission after hospital discharge." ], "exact_answer": [ [ "Length of stay" ], [ "Acuity of admission" ], [ "Comorbidity" ], [ "Emergency visits in the previous 6 months" ] ], "type": "list", "id": "5e2b109cfbd6abf43b000002", "snippets": [ { "offsetInBeginSection": 274, "offsetInEndSection": 421, "text": "The LACE index is a simple tool with 4 parameters: Length of stay, Acuity of admission, Comorbidity, and Emergency visits in the previous 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29148921", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 701, "text": "he objective of this study was to calculate the rate of 30-day readmissions and evaluate the accuracy of the LACE index (length of stay, acuity of admission, co-morbidities, and emergency department visits within the last 6 months) for 30-day readmissions in a general hospital population of COPD patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29343987", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 526, "text": "Study aims were to evaluate if the revised LACE (length of stay, acuity of admission, Charlson Comorbidity Index, emergency department visits in the past 6 months) index would identify high risk of early readmission (\u226430 days postdischarge), and if postdischarge clinic and community services follow-up would reduce readmission rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29634597", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 480, "text": "This research was focused on the evaluation of LACE Index for Readmission - Length of stay (days), Acute (emergent) admission, Charlson Comorbidity Index and number of ED visits within six months (LACE) and Patients At Risk of Hospital Readmission (PARR) using New Zealand hospital admissions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30040677", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 991, "text": "Data on age, gender, diagnoses, 30-day hospital readmission, discharge medications and variables in the HOSPITAL score (Haemoglobin level at discharge, Oncology at discharge, Sodium level at discharge, Procedure during hospitalisation, Index admission, number of hospital Admissions, Length of stay) and LACE index (Length of stay, Acute/emergent admission, Charlson comorbidity index score, Emergency department visits in previous 6 months), which have higher predictability for readmission were extracted and matched for analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30279159", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1566, "text": "In addition to the variables included in the LACE index (length of stay in hospital [L], acuity of admission [A], comorbidity [C] and emergency department utilization in the 6 months before admission [E]), the LACE+ index incorporated patient age and sex, teaching status of the discharge hospital, acute diagnoses and procedures performed during the index admission, number of days on alternative level of care during the index admission, and number of elective and urgent admissions to hospital in the year before the index admission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23696773", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 684, "text": "The objective of this study was to calculate the rate of 30-day readmissions and evaluate the accuracy of the LACE index ( length of stay , acuity of admission , co-morbidities , and emergency department visits within the last 6 months ) for 30-day readmissions in a general hospital population of COPD patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29343987", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "BACKGROUND\nThe LACE+ index (Length of stay, Acuity of admission, Charlson Comorbidity Index score, and Emergency department [ED] visits in the past 6 months) is a tool used to predict 30-day readmissions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30926557", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1562, "text": "In addition to the variables included in the LACE index (length of stay in hospital [L], acuity of admission [A], comorbidity [C] and emergency department utilization in the 6 months before admission [E]), the LACE+ index incorporated patient age and sex, teaching status of the discharge hospital, acute diagnoses and procedures performed during the index admission, number of days on alternative level of care during the index admission, and number of elective and urgent admissions to hospital in the year before the index admission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23696773", "endSection": "abstract" }, { "offsetInBeginSection": 1025, "offsetInEndSection": 1561, "text": "In addition to the variables included in the LACE index (length of stay in hospital [L], acuity of admission [A], comorbidity [C] and emergency department utilization in the 6 months before admission [E]), the LACE+ index incorporated patient age and sex, teaching status of the discharge hospital, acute diagnoses and procedures performed during the index admission, number of days on alternative level of care during the index admission, and number of elective and urgent admissions to hospital in the year before the index admission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23696773", "endSection": "abstract" } ] }, { "body": "Which drugs are included in GI cocktail?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2202240", "http://www.ncbi.nlm.nih.gov/pubmed/15219296", "http://www.ncbi.nlm.nih.gov/pubmed/22463973", "http://www.ncbi.nlm.nih.gov/pubmed/24791662", "http://www.ncbi.nlm.nih.gov/pubmed/7492037", "http://www.ncbi.nlm.nih.gov/pubmed/14585449" ], "ideal_answer": [ "\"GI cocktail\" is a mixture of liquid antacid, viscous lidocaine, and an anticholinergic." ], "exact_answer": [ [ "liquid antacid" ], [ "viscous lidocaine" ], [ "anticholinergic" ] ], "type": "list", "id": "5e2f906ffbd6abf43b00002c", "snippets": [ { "offsetInBeginSection": 461, "offsetInEndSection": 933, "text": "AIM: A systematic review of the literature was conducted to locate and evaluate clinical trials comparing the use of an oral gastrointestinal (GI) cocktail (oral viscous lidocaine/ antacid \u00b1 anticholinergic) to standard diagnostic protocols (serial electrocardiograms (ECGs), serial biomarkers, imaging and/ or provocative testing) to differentiate emergency patients presenting with acute chest pain caused by gastro-oesophageal disease from those with other aetiologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24791662", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 289, "text": "Despite the traditional \"GI cocktail\" (GI indicates gastrointestinal), an intravenous (IV) proton pump inhibitor (PPI), a novel acid-lowering drug, has recently been used to treat this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22463973", "endSection": "abstract" }, { "offsetInBeginSection": 619, "offsetInEndSection": 826, "text": " Selected patients with severe dyspeptic pain were randomized to treatment with a placebo, antacid, and antispasmodic (conventional group) or IV pantoprazole, antacid, and antispasmodic (pantoprazole group).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22463973", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 281, "text": "This was a prospective randomized, single-blinded comparison between Benzocaine and Lidocaine as the topical anesthetic in a gastrointestinal (GI) cocktail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15219296", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 543, "text": "Patients were randomized to equivalent doses of either Benzocaine or viscous Lidocaine in addition to 30 cc of Maalox and 10 cc of Donnatal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15219296", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 481, "text": "This study compared three combinations commonly given for dyspepsia. The study was a prospective, randomized, double-blinded trial comparing antacid (group 1); antacid + Donnatal (group 2); antacid + Donnatal + viscous lidocaine (group 3) for acute treatment of dyspepsia in the ED. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14585449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "STUDY OBJECTIVE: To determine practice patterns regarding administration of the \"GI cocktail\" (a mixture of liquid antacid, viscous lidocaine, and an anticholinergic) in the emergency department in a single hospital and the responses and final dispositions of patients who received the cocktails.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7492037", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 492, "text": "Patients presenting to the ED with dyspeptic symptoms were randomized to receive 30 mL of antacid (Mylanta II), or 30 mL of antacid plus 15 mL of 2% viscous lidocaine (GI cocktail). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2202240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "STUDY OBJECTIVE\n\nTo determine practice patterns regarding administration of the \"GI cocktail\" (a mixture of liquid antacid, viscous lidocaine, and an anticholinergic) in the emergency department in a single hospital and the responses and final dispositions of patients who received the cocktails.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7492037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "STUDY OBJECTIVE\nTo determine practice patterns regarding administration of the \"GI cocktail\" (a mixture of liquid antacid, viscous lidocaine, and an anticholinergic) in the emergency department in a single hospital and the responses and final dispositions of patients who received the cocktails.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7492037", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 296, "text": "OBJECTIVE: To determine practice patterns regarding administration of the \"GI cocktail\" (a mixture of liquid antacid, viscous lidocaine, and an anticholinergic) in the emergency department in a single hospital and the responses and final dispositions of patients who received the cocktails.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7492037", "endSection": "abstract" } ] }, { "body": "Is AZD5153 active in prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30308485" ], "ideal_answer": [ "Yes, AZD5153 was shown to be effective in treatment of prostate cancer.", "Yes. AZD5153, a novel BRD4 inhibitor, inhibits prostate cancer cell growth in vitro and in vivo. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells." ], "exact_answer": "yes", "type": "yesno", "id": "5e2b253ffbd6abf43b000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "title" }, { "offsetInBeginSection": 18, "offsetInEndSection": 1666, "text": "Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor.METHODS: Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153's activity in vivo.RESULTS: AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206.CONCLUSION: Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 941, "text": "AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1672, "text": "CONCLUSION\n\nTogether, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1119, "text": "AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 856, "text": "RESULTS\n\nAZD5153 inhibited proliferation and survival of established and primary prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 851, "text": "RESULTS AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 936, "text": "AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1114, "text": "AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 1527, "offsetInEndSection": 1665, "text": "CONCLUSION Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "title" }, { "offsetInBeginSection": 856, "offsetInEndSection": 941, "text": "AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30308485", "endSection": "abstract" } ] }, { "body": "Is GRG5 involved only in late embryonic mouse development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30214018" ], "ideal_answer": [ "No. Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in both early and late embryonic mouse development." ], "exact_answer": "no", "type": "yesno", "id": "5e2b3784fbd6abf43b000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 639, "text": "Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30214018", "endSection": "abstract" } ] }, { "body": "Are astronauts in higher risk for developing cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29855508", "http://www.ncbi.nlm.nih.gov/pubmed/29644336" ], "ideal_answer": [ "No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation." ], "exact_answer": "no", "type": "yesno", "id": "5e480909d14c9f295d000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Understanding space radiation health effects is critical due to potential increased morbidity and mortality following spaceflight. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29855508", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 991, "text": " No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29855508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644336", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of a drug Elagolix.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30194661", "http://www.ncbi.nlm.nih.gov/pubmed/29889764", "http://www.ncbi.nlm.nih.gov/pubmed/29335207", "http://www.ncbi.nlm.nih.gov/pubmed/28737050", "http://www.ncbi.nlm.nih.gov/pubmed/25249568", "http://www.ncbi.nlm.nih.gov/pubmed/29946962", "http://www.ncbi.nlm.nih.gov/pubmed/19033369", "http://www.ncbi.nlm.nih.gov/pubmed/28525302", "http://www.ncbi.nlm.nih.gov/pubmed/31749075", "http://www.ncbi.nlm.nih.gov/pubmed/30320043", "http://www.ncbi.nlm.nih.gov/pubmed/28255765", "http://www.ncbi.nlm.nih.gov/pubmed/30303923", "http://www.ncbi.nlm.nih.gov/pubmed/29476499", "http://www.ncbi.nlm.nih.gov/pubmed/28323948", "http://www.ncbi.nlm.nih.gov/pubmed/30551159" ], "ideal_answer": [ "Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist. It is in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids." ], "type": "summary", "id": "5e2900368b3851296d000001", "snippets": [ { "offsetInBeginSection": 604, "offsetInEndSection": 767, "text": "Compound 12c showed potent and prolonged LH suppression after a single dose was orally administered in castrated monkeys compared to a known antagonist, Elagolix. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "INTRODUCTION: Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29476499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "OBJECTIVE: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29889764", "endSection": "abstract" }, { "offsetInBeginSection": 1504, "offsetInEndSection": 1667, "text": "Phase III trials on elagolix, a new oral GnRH antagonist but non-inferiority RCT data are required to compare elagolix with first-line therapies for endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29946962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Elagolix (ORILISSA\u2122), an orally bioavailable, second-generation, non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, is being developed AbbVie and Neurocrine Biosciences for the treatment of reproductive hormone-dependent disorders in women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30194661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "OBJECTIVE: To evaluate elagolix, an oral gonadotropin-releasing hormone receptor antagonist, alone or with add-back therapy, in premenopausal women with heavy menstrual bleeding (greater than 80 mL per month) associated with uterine leiomyomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30303923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28255765", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30551159", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 234, "text": "Elagolix is a novel, orally available nonpeptide GnRH antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19033369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28525302", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Elagolix, an Oral GnRH Antagonist for Endometriosis-Associated Pain: A Randomized Controlled Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30320043", "endSection": "title" }, { "offsetInBeginSection": 129, "offsetInEndSection": 228, "text": "In addition to already established medications, a new GnRH antagonist, elagolix, is in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28737050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Clinical Pharmacology of Elagolix: An Oral Gonadotropin-Releasing Hormone Receptor Antagonist for Endometriosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31749075", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 927, "text": "Context: Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women.Objective: We evaluated the pharmacokinetics and pharmacodynamics of elagolix.Design, Setting, and Participants: This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit.Interventions: Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days.Main Outcome Measures: Main outcome measures were elagolix pharmacokinetics, suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and adverse events.Results: Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28323948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25249568", "endSection": "title" }, { "offsetInBeginSection": 796, "offsetInEndSection": 959, "text": "While elagolix may have an advantage over established GnRH agonists, in that it does not lead to a 'flare-up' effect, it too, takes a toll on bone mineral density.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28737050", "endSection": "abstract" } ] }, { "body": "Describe mechanism of action of volanesorsen.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30102092", "http://www.ncbi.nlm.nih.gov/pubmed/29889589", "http://www.ncbi.nlm.nih.gov/pubmed/29096837", "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "http://www.ncbi.nlm.nih.gov/pubmed/29124482", "http://www.ncbi.nlm.nih.gov/pubmed/26848137", "http://www.ncbi.nlm.nih.gov/pubmed/30403015", "http://www.ncbi.nlm.nih.gov/pubmed/29842811", "http://www.ncbi.nlm.nih.gov/pubmed/28300080", "http://www.ncbi.nlm.nih.gov/pubmed/29547399", "http://www.ncbi.nlm.nih.gov/pubmed/31350288", "http://www.ncbi.nlm.nih.gov/pubmed/28209220", "http://www.ncbi.nlm.nih.gov/pubmed/31032598", "http://www.ncbi.nlm.nih.gov/pubmed/30596391" ], "ideal_answer": [ "Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. It has been shown to decrease TGs by 70-80%." ], "type": "summary", "id": "5e2905da8b3851296d000009", "snippets": [ { "offsetInBeginSection": 1275, "offsetInEndSection": 1393, "text": " Clinical trials with Volanesorsen, an APOC3 antisense oligonucleotide, report very promising lipid-lowering outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547399", "endSection": "abstract" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1045, "text": "An antisense oligonucleotide to apolipoprotein-C3, volanesorsen has been shown to decrease TGs by 70-80% and possibly to reduce rates of pancreatitis admissions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29842811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "BACKGROUND: Volanesorsen, an investigational inhibitor of apoC-III synthesis, significantly reduced triglyceride levels in clinical trials in patients with familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by marked chylomicronemia leading to a spectrum of symptoms, including recurrent abdominal pain and episodes of potentially fatal acute pancreatitis (AP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29889589", "endSection": "abstract" }, { "offsetInBeginSection": 1774, "offsetInEndSection": 2144, "text": "Further studies should address the effect of omega-3 PUFAs alone or with other lipid-lowering drugs in order to provide a final answer whether apo C-III could be an important target for prevention of cardiovascular disease New apo C-III antisense oligonucleotide drug (Volanesorsen) showed to be promising in decreasing elevated TGs by reducing levels of apo C-III mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30102092", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 969, "text": "Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30403015", "endSection": "abstract" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1335, "text": "Some new drugs are on the horizon, such as volanesorsen (which targets apolipoprotein C-III), pemafibrate, and others. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28300080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "ApoCIII as a Cardiovascular Risk Factor and Modulation by the Novel Lipid-Lowering Agent Volanesorsen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124482", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "endSection": "title" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1761, "text": "Discovery of the ApoCIII inhibitor volanesorsen opens a new era of lipid-lowering drugs for reduction in TG and potentially for reduction in LDL-C. Herein, this review will provide an update on the pathophysiology of ApoCIII-linked atherosclerosis and the development of the first drug to target ApoCIII, volanesorsen, as a promising lipid-lowering agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124482", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1513, "text": "CONCLUSIONS\n\nVolanesorsen reduced plasma apoC-III and TG while raising HDL-C levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "OBJECTIVE\n\nTo determine the effects of volanesorsen (ISIS 304801), a second-generation 2'-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein (apo)C-III, on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 929, "text": "Volanesorsen is an experimental antisense oligonucleotide that inhibits translation of Apo-CIII mRNA, thereby substantially lowering plasma levels of Apo-CIII and triglycerides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30596391", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1405, "text": "RECENT FINDINGS\n\nEvidence is now emerging that volanesorsen, a second-generation antisense oligonucleotide drug targeting ApoCIII messenger RNA resulting in decreases in TG in patients with familial chylomicronemia syndrome, severe hypertriglyceridemia, and metabolic dyslipidemia with type 2 diabetes giving support to the hypothesis that ApoCIII is a powerful inhibitor of LPL, and when reduced, endogenous clearance of TRLs can result in substantial reductions in TG levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26848137", "endSection": "title" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1506, "text": "CONCLUSIONS Volanesorsen reduced plasma apoC-III and TG while raising HDL-C levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "endSection": "abstract" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1334, "text": "Some new drugs are on the horizon, such as volanesorsen (which targets apolipoprotein C-III), pemafibrate, and others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28300080", "endSection": "abstract" }, { "offsetInBeginSection": 1236, "offsetInEndSection": 1357, "text": "Some new drugs are on the horizon , such as volanesorsen ( which targets apolipoprotein C-III) , pemafibrate , and others", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28300080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "To determine the effects of volanesorsen ( ISIS 304801) , a second-generation 2'-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein ( apo)C-III , on triglyceride ( TG ) levels and insulin resistance in patients with type 2 diabetes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Volanesorsen (previously known as ISIS 304801) is a 20-nucleotide partially 2'-O-(2-methoxyethyl) (2'-MOE)-modified antisense oligonucleotide (ASO) gapmer, which was recently approved in the European Union as a novel, first-in-class treatment in the reduction of triglyceride levels in patients with familial chylomicronemia syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31350288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "BACKGROUND\nVolanesorsen, an investigational inhibitor of apoC-III synthesis, significantly reduced triglyceride levels in clinical trials in patients with familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by marked chylomicronemia leading to a spectrum of symptoms, including recurrent abdominal pain and episodes of potentially fatal acute pancreatitis (AP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29889589", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 892, "text": "Recently, volanesorsen as a promising ApoIII inhibitor was shown to improve the lipid profile in patients with diabetic dyslipidemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31032598", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Contribution of ApoCIII to Diabetic Dyslipidemia and Treatment With Volanesorsen.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31032598", "endSection": "title" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1109, "text": "Herein, this paper will review recent advance in pathophysiology of diabetic dyslipidemia and the role of ApoCIII in this condition, with focus on describing a novel drug volanesorsen as potential treatment strategy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31032598", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 822, "text": "CONCLUSIONS: Volanesorsen reduced plasma apoC-III and TG while raising HDL-C levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1759, "text": "Discovery of the ApoCIII inhibitor volanesorsen opens a new era of lipid-lowering drugs for reduction in TG and potentially for reduction in LDL-C. Herein, this review will provide an update on the pathophysiology of ApoCIII-linked atherosclerosis and the development of the first drug to target ApoCIII, volanesorsen, as a promising lipid-lowering agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124482", "endSection": "abstract" }, { "offsetInBeginSection": 1802, "offsetInEndSection": 1967, "text": "ApoC-III inhibition by volanesorsen reduced plasma levels of apoC-II, apoC-III, triacylglycerols, and diacylglycerols, and increased apoA-I, apoA-II, and apoM (all p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28209220", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1074, "text": "Changes in apolipoprotein and lipid levels following treatment with volanesorsen, a second-generation antisense drug targeting apoC-III, were determined in 2 human intervention trials, one of which was randomized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28209220", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 990, "text": "The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apo-CIII production and triglyceride concentrations and is being currently evaluated in phase 3 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29096837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "Volanesorsen (previously known as ISIS 304801) is a 20-nucleotide partially 2'-O (2 methoxyethyl) (2' MOE) modified antisense oligonucleotide (ASO) gapmer and was recently approved in the European Union as a novel, first in class treatment for reduction of triglyceride levels in patients with Familial Chylomicronemia Syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31350288", "endSection": "abstract" }, { "offsetInBeginSection": 758, "offsetInEndSection": 891, "text": "Recently, volanesorsen as a promising ApoIII inhibitor was shown to improve the lipid profile in patients with diabetic dyslipidemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31032598", "endSection": "abstract" } ] }, { "body": "What is the cyberknife used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28544809", "http://www.ncbi.nlm.nih.gov/pubmed/28298046", "http://www.ncbi.nlm.nih.gov/pubmed/28849326" ], "ideal_answer": [ "CyberKnife(r) is a robotic stereotactic radiotherapy system" ], "exact_answer": [ "CyberKnife\u00ae is a robotic stereotactic radiotherapy system" ], "type": "factoid", "id": "5e480da0d14c9f295d000006", "snippets": [ { "offsetInBeginSection": 694, "offsetInEndSection": 854, "text": "Stereotactic radiosurgery using CyberKnife\u00ae seems to be an efficient and safe therapeutic option for malignant melanomas affecting the choroid and ciliary body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28849326", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 262, "text": "Stereotactic radiosurgery (SRS) has emerged as a principal alternative to microresection for small- and medium-sized CSHs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28298046", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 215, "text": "CyberKnife\u00ae is a robotic stereotactic radiotherapy system. The aim of this study is to evaluate the effectiveness and the safety of CyberKnife\u00ae on treating head and neck paragangliomas and to report our results", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28544809", "endSection": "abstract" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1563, "text": "Stereotactic radiotherapy is a good alternative to surgery for the treatment of head and neck paragangliomas coming up with a clear benefit of acute and late side effects. CyberKnife\u00ae seems to be a safe and efficient system treating head and neck paragangliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28544809", "endSection": "abstract" } ] }, { "body": "Is Niraparib effective for ovarian cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29251678", "http://www.ncbi.nlm.nih.gov/pubmed/28474297", "http://www.ncbi.nlm.nih.gov/pubmed/29081841", "http://www.ncbi.nlm.nih.gov/pubmed/29327913", "http://www.ncbi.nlm.nih.gov/pubmed/30073633", "http://www.ncbi.nlm.nih.gov/pubmed/29322231", "http://www.ncbi.nlm.nih.gov/pubmed/29397193", "http://www.ncbi.nlm.nih.gov/pubmed/27810860", "http://www.ncbi.nlm.nih.gov/pubmed/29911447", "http://www.ncbi.nlm.nih.gov/pubmed/28994564", "http://www.ncbi.nlm.nih.gov/pubmed/27717299", "http://www.ncbi.nlm.nih.gov/pubmed/30293481", "http://www.ncbi.nlm.nih.gov/pubmed/28299955" ], "ideal_answer": [ "Yes. Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is approved by the United States Food and Drug Administration and the European Medicines Agency for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy." ], "exact_answer": "yes", "type": "yesno", "id": "5e2906948b3851296d00000a", "snippets": [ { "offsetInBeginSection": 920, "offsetInEndSection": 1064, "text": "Niraparib and olaparib have been approved by the US FDA for maintenance therapy after partial or complete remission in recurrent ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28994564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "PURPOSE OF REVIEW: The recent United States Food and Drug Administration approvals of niraparib and olaparib as maintenance monotherapy for platinum-sensitive, high-grade ovarian cancers independent of BRCA status reflect a willingness to seek indications for poly-ADP-ribose polymerase (PARP) inhibitors beyond cancers with deleterious breast cancer 1 and breast cancer 2 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29251678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "PURPOSE: Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved in the United States for maintenance treatment of adult patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322231", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 783, "text": "Indeed, three PARP1 inhibitors (Olaparib, Rucaparib, and Niraparib) have recently been approved by the Food and Drug Administration for the treatment of ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29327913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29397193", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 913, "text": "Niraparib is a poly adenosine diphosphate ribose polymerase inhibitor that has shown to be clinically effective as maintenance therapy in patients with platinum sensitive, recurrent ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30293481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27717299", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Niraparib for the treatment of ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29911447", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND\n\nNiraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27717299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Niraparib Slows Ovarian Cancer Progression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Niraparib for the treatment of ovarian cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28299955", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "INTRODUCTION\n\nNiraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29911447", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 688, "text": "The role of niraparib as maintenance following frontline platinum-based chemotherapy as well as in the treatment of recurrent high-grade serous ovarian cancer is an active area of investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29911447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Niraparib in ovarian cancer: results to date and clinical potential.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29081841", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Niraparib , an orally available selective inhibitor of poly(adenosine diphosphate-ribose ) polymerase ( PARP) , is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene ( BRCA) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29911447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Results from a phase III trial indicate that maintenance therapy with the PARP inhibitor niraparib is more effective than placebo in slowing the progression of recurrent platinum-sensitive ovarian cancer . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27810860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Niraparib (Zejula\u00ae), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30073633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29911447", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1372, "text": "Current evidence suggests that niraparib is an effective new option with a manageable tolerability profile for the maintenance treatment of recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults, with or without BRCA1/2 mutation or HRD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30073633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Oral niraparib, a highly-selective, potent poly(ADP-ribose) polymerase (PARP)-1 and PARP-2 inhibitor, is approved in the USA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28474297", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1203, "text": "This article summarizes the milestones in the development of niraparib leading to its first global approval for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28474297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Niraparib (Zejula ), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30073633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "INTRODUCTION: Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29911447", "endSection": "abstract" } ] }, { "body": "Which portal has been developed to explore protein-protein interactions in cancer cell lines?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29186335", "http://www.ncbi.nlm.nih.gov/pubmed/31583637" ], "ideal_answer": [ "The OncoPPi Portal has been developed as an interactive web resource that allows investigators to access, manipulate and interpret a high-quality cancer-focused network of protein-protein interactions (PPIs) experimentally detected in cancer cell lines. To facilitate prioritization of PPIs for further biological studies, this resource combines network connectivity analysis, mutual exclusivity analysis of genomic alterations, cellular co-localization of interacting proteins and domain-domain interactions. Estimates of PPI essentiality allow users to evaluate the functional impact of PPI disruption on cancer cell proliferation. Furthermore, connecting the OncoPPi network with the approved drugs and compounds in clinical trials enables discovery of new tumor dependencies to inform strategies to interrogate undruggable targets like tumor suppressors. The OncoPPi Portal serves as a resource for the cancer research community to facilitate discovery of cancer targets and therapeutic development." ], "exact_answer": [ "The OncoPPi Portal" ], "type": "factoid", "id": "5e2e136bfbd6abf43b000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The OncoPPi Portal: an integrative resource to explore and prioritize protein-protein interactions for cancer target discovery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29186335", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1842, "text": "As cancer genomics initiatives move toward comprehensive identification of genetic alterations in cancer, attention is now turning to understanding how interactions among these genes lead to the acquisition of tumor hallmarks. Emerging pharmacological and clinical data suggest a highly promising role of cancer-specific protein-protein interactions (PPIs) as druggable cancer targets. However, large-scale experimental identification of cancer-related PPIs remains challenging, and currently available resources to explore oncogenic PPI networks are limited.Results: Recently, we have developed a PPI high-throughput screening platform to detect PPIs between cancer-associated proteins in the context of cancer cells. Here, we present the OncoPPi Portal, an interactive web resource that allows investigators to access, manipulate and interpret a high-quality cancer-focused network of PPIs experimentally detected in cancer cell lines. To facilitate prioritization of PPIs for further biological studies, this resource combines network connectivity analysis, mutual exclusivity analysis of genomic alterations, cellular co-localization of interacting proteins and domain-domain interactions. Estimates of PPI essentiality allow users to evaluate the functional impact of PPI disruption on cancer cell proliferation. Furthermore, connecting the OncoPPi network with the approved drugs and compounds in clinical trials enables discovery of new tumor dependencies to inform strategies to interrogate undruggable targets like tumor suppressors. The OncoPPi Portal serves as a resource for the cancer research community to facilitate discovery of cancer targets and therapeutic development.Availability and implementation: The OncoPPi Portal is available at http://oncoppi.emory.edu.Contact: andrey.ivanov@emory.edu or hfu@emory.edu.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29186335", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 951, "text": "Here, we present the OncoPPi Portal, an interactive web resource that allows investigators to access, manipulate and interpret a high-quality cancer-focused network of PPIs experimentally detected in cancer cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29186335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Explore Protein-Protein Interactions for Cancer Target Discovery Using the OncoPPi Portal", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583637", "endSection": "title" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1456, "text": "The established network of oncogenic PPIs , termed the OncoPPi network , is available through the OncoPPi Portal , an interactive web resource that allows to access and interpret a high-quality cancer-focused network of PPIs experimentally detected in cancer cell lines integrated with the analysis of mutual exclusivity of genomic alterations , cellular co-localization of interacting proteins , domain-domain interactions , and therapeutic connectivity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Explore Protein-Protein Interactions for Cancer Target Discovery Using the OncoPPi Portal.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583637", "endSection": "title" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1557, "text": "This chapter presents a guide to explore the OncoPPi network using the OncoPPi Portal to facilitate cancer biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583637", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1441, "text": "The established network of oncogenic PPIs, termed the OncoPPi network, is available through the OncoPPi Portal, an interactive web resource that allows to access and interpret a high-quality cancer-focused network of PPIs experimentally detected in cancer cell lines integrated with the analysis of mutual exclusivity of genomic alterations, cellular co-localization of interacting proteins, domain-domain interactions, and therapeutic connectivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583637", "endSection": "abstract" } ] }, { "body": "Are genes that escape X-chromosome inactivation related to mental impairment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24023392", "http://www.ncbi.nlm.nih.gov/pubmed/17383248" ], "ideal_answer": [ "Yes. Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving.", "Yes, most of the X-chromosome inactivation genes shown to be associated with mental retardation are those encoding transcription factors involved in intellectual disability, such as X-linked Na(+) /H(+) exchanger 2 (NHE2), Sox 10, Endothelin-3 (EDN3) and SOX10. Some X- chromosome inactivation gene variants are associated with intellectual disability but not others.", "Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving. The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes." ], "exact_answer": "yes", "type": "yesno", "id": "5c72768a7c78d6947100006c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Mutation screening of the MECP2 gene in a large cohort of 613 fragile-X negative patients with mental retardation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17383248", "endSection": "title" }, { "offsetInBeginSection": 821, "offsetInEndSection": 1079, "text": "The first one, the double nucleotide substitution c.1162_1163delinsTA leading to a premature stop codon (p.Pro388X) was found in a female patient with random X-inactivation, presenting with borderline mental impairment without any features of Rett syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17383248", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1386, "text": "the c.679C>G substitution, changing a glutamine to a glutamate in the transcriptional repression functional domain (p.Gln227Glu), was found in a female patient with a moderately biased X-chromosome inactivation profile and presenting with mild intellectual delay and minor psychotic features", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17383248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24023392", "endSection": "title" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1168, "text": " The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24023392", "endSection": "abstract" } ] }, { "body": "Which biological process takes place in nuclear speckles?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12923522", "http://www.ncbi.nlm.nih.gov/pubmed/12826600", "http://www.ncbi.nlm.nih.gov/pubmed/12002677", "http://www.ncbi.nlm.nih.gov/pubmed/29496966", "http://www.ncbi.nlm.nih.gov/pubmed/23934081", "http://www.ncbi.nlm.nih.gov/pubmed/27239700", "http://www.ncbi.nlm.nih.gov/pubmed/30032211", "http://www.ncbi.nlm.nih.gov/pubmed/29773831", "http://www.ncbi.nlm.nih.gov/pubmed/30194269" ], "ideal_answer": [ "Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells. They serve as splicing factor storage sites and play important roles in regulation of pre-mRNA splicing." ], "exact_answer": [ "mRNA processing", "mRNA splicing" ], "type": "factoid", "id": "5c74266a7c78d694710000a2", "snippets": [ { "offsetInBeginSection": 188, "offsetInEndSection": 295, "text": "Here we demonstrate that mRNAs containing ALREX-promoting elements are trafficked through nuclear speckles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23934081", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 893, "text": "Finally, we demonstrate that mRNAs lacking a poly(A)-tail are not efficiently exported by the ALREX pathway and show enhanced association with nuclear speckles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23934081", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 521, "text": " In a previous study (Melc\u00e1k et al., 2001), it has been shown that the pre-spliceosomal assembly on microinjected splicing-competent precursor mRNA takes place in the speckles, and it has been suggested that the targeting of RNA into speckes consists of two interdependent steps, namely the diffusion process, followed by the energy-dependent translocation of RNA into the speckles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12002677", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 445, "text": "Nuclear speckles, a unique nuclear subcompartment, accumulate a family of proteins, namely, serine- and arginine-rich (SR) proteins. They play important roles in regulation of pre-mRNA splicing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12826600", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 332, "text": " Here we show that C3G localizes to SC35-positive nuclear speckles and regulates splicing activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29496966", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1385, "text": "Our results identify C3G and Rap1 as novel components of nuclear speckles and a role for C3G in regulating cellular RNA splicing activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29496966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29773831", "endSection": "title" }, { "offsetInBeginSection": 470, "offsetInEndSection": 552, "text": "These results suggest that exosomal mRNA degradation mostly occurs outside of NSs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30032211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Nuclear speckles (NSs) serve as splicing factor storage sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30194269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12923522", "endSection": "abstract" } ] }, { "body": "What is the effect of HMGB2 loss on CTCF clustering?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "http://www.ncbi.nlm.nih.gov/pubmed/27226577" ], "ideal_answer": [ "Depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CTCF. Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing HMGB2 rescues these effects." ], "type": "summary", "id": "5e2d7fabfbd6abf43b00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "title" }, { "offsetInBeginSection": 589, "offsetInEndSection": 1016, "text": "We show that nuclear depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CTCF. Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing HMGB2 rescues these effects. Our data suggest that HMGB2-mediated genomic reorganization constitutes a primer for the ensuing senescent program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 900, "text": "Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing HMGB2 rescues these effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 748, "text": "We show that nuclear depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CTCF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "title" }, { "offsetInBeginSection": 599, "offsetInEndSection": 757, "text": "We show that nuclear depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CTCF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 911, "text": "Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling , while ectopically expressing HMGB2 rescues these effects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 901, "text": "Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing HMGB2 rescues these effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 749, "text": "We show that nuclear depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CTCF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706538", "endSection": "abstract" } ] }, { "body": "Has LB-100 been tested in clinical trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28039265" ], "ideal_answer": [ "Yes, a phase I trial has been performed to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors." ], "exact_answer": "yes", "type": "yesno", "id": "5e29fe76aa19d74431000007", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 227, "text": "To determine the MTD and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28039265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28039265", "endSection": "title" } ] }, { "body": "Which algorithms have been developed for analysing CRISPR/Cas9 knockout screens data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25476604", "http://www.ncbi.nlm.nih.gov/pubmed/25428347" ], "ideal_answer": [ "HiTSelect and MAGeCK (Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout)" ], "exact_answer": [ [ "HiTSelect" ], [ "MAGeCK", "Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout" ] ], "type": "list", "id": "5e307a05fbd6abf43b000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25428347", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1098, "text": "Genetic screens of an unprecedented scale have recently been made possible by the availability of high-complexity libraries of synthetic oligonucleotides designed to mediate either gene knockdown or gene knockout, coupled with next-generation sequencing. However, several sources of random noise and statistical biases complicate the interpretation of the resulting high-throughput data. We developed HiTSelect, a comprehensive analysis pipeline for rigorously selecting screen hits and identifying functionally relevant genes and pathways by addressing off-target effects, controlling for variance in both gene silencing efficiency and sequencing depth of coverage and integrating relevant metadata. We document the superior performance of HiTSelect using data from both genome-wide RNAi and CRISPR/Cas9 screens. HiTSelect is implemented as an open-source package, with a user-friendly interface for data visualization and pathway exploration. Binary executables are available at http://sourceforge.net/projects/hitselect/, and the source code is available at https://github.com/diazlab/HiTSelect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25428347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25476604", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 767, "text": "We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including EGFR in vemurafenib-treated A375 cells harboring a BRAF mutation. MAGeCK also detected cell type-specific essential genes, including BCR and ABL1, in KBM7 cells bearing a BCR-ABL fusion, and IGF1R in HL-60 cells, which depends on the insulin signaling pathway for proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25476604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25476604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25476604", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 813, "text": "We document the superior performance of HiTSelect using data from both genome-wide RNAi and CRISPR/Cas9 screens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25428347", "endSection": "abstract" } ] }, { "body": "Which cells are affected in radiation-induced leukemias?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17179481", "http://www.ncbi.nlm.nih.gov/pubmed/9209408" ], "ideal_answer": [ "Hemopoietic stem cells, the possible target cells for radiation-induced leukemias." ], "type": "summary", "id": "5e48136dd14c9f295d000008", "snippets": [ { "offsetInBeginSection": 870, "offsetInEndSection": 961, "text": "Number of hemopoietic stem cells, the possible target cells for radiation-induced leukemias", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9209408", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 494, "text": "risks of high-dose radiation-induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17179481", "endSection": "abstract" }, { "offsetInBeginSection": 2140, "offsetInEndSection": 2435, "text": "An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, with reasonable accuracy, risks for radiation-induced leukemia associated with exposure to therapeutic doses of radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17179481", "endSection": "abstract" } ] }, { "body": "PDQ39 questionnaires is design for which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29670566", "http://www.ncbi.nlm.nih.gov/pubmed/24035927", "http://www.ncbi.nlm.nih.gov/pubmed/30363378", "http://www.ncbi.nlm.nih.gov/pubmed/18543333", "http://www.ncbi.nlm.nih.gov/pubmed/23346238", "http://www.ncbi.nlm.nih.gov/pubmed/28805568", "http://www.ncbi.nlm.nih.gov/pubmed/28122431", "http://www.ncbi.nlm.nih.gov/pubmed/30108543", "http://www.ncbi.nlm.nih.gov/pubmed/29542093", "http://www.ncbi.nlm.nih.gov/pubmed/15778909", "http://www.ncbi.nlm.nih.gov/pubmed/28980176", "http://www.ncbi.nlm.nih.gov/pubmed/28770096", "http://www.ncbi.nlm.nih.gov/pubmed/29644334", "http://www.ncbi.nlm.nih.gov/pubmed/28290191", "http://www.ncbi.nlm.nih.gov/pubmed/17702633", "http://www.ncbi.nlm.nih.gov/pubmed/21163736", "http://www.ncbi.nlm.nih.gov/pubmed/16258207", "http://www.ncbi.nlm.nih.gov/pubmed/29215823", "http://www.ncbi.nlm.nih.gov/pubmed/23323136", "http://www.ncbi.nlm.nih.gov/pubmed/20347841", "http://www.ncbi.nlm.nih.gov/pubmed/16763974" ], "ideal_answer": [ "PDQ39 is Parkinson's Disease Questionnaire that is used for assessment of quality of life in patients with Parkinson's Disease." ], "exact_answer": [ "Parkinson's Disease" ], "type": "factoid", "id": "5e2b1ed9fbd6abf43b000005", "snippets": [ { "offsetInBeginSection": 752, "offsetInEndSection": 1065, "text": "The outcomes assessed were motor symptoms with Unified PD Rating Scale III (UPDRSIII), functional mobility with Timed Up and Go Test (TUG), endurance with 6 min walking test (6MWT), freezing of gait with Freezing of Gait Questionnaire (FOG_Q), walking velocity with GAITRite and QL with PD Questionnaire (PDQ39). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28980176", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 968, "text": " They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29215823", "endSection": "abstract" }, { "offsetInBeginSection": 1463, "offsetInEndSection": 1576, "text": "The median PD questionnaire 39-score index (PDQ39-SI) was 23.22% and the most affected dimension was \"mobility.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29670566", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1543, "text": "In the 43% of cases in whom oral therapy was changed, total UPDRS improved significantly (effect size\u2009=\u20098) as did the PDQ39 in cases reaching target. NMS Quest and MOCA scores also improved significantly. This study shows that many people in a representative cohort of PD would benefit from objective assessment and treatment of their PD features against a target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644334", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 551, "text": "Here, we applied a novel diffusion-weighted imaging approach, diffusion MRI connectometry, to investigate the correlation of quality of life, evaluated by Parkinson's Disease Questionnaire (PDQ39) with the white matter structural connectivity in 27 non-demented PD patients (disease duration of 5.3\u00a0\u00b1\u00a02.9\u00a0years, H and Y stage\u00a0=\u00a01.5\u00a0\u00b1\u00a00.6, UPDRS-III\u00a0=\u00a013.7\u00a0\u00b1\u00a06.5, indicating unilateral and mild motor involvement). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29542093", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 690, "text": "The present study aimed to assess the beneficial and side effects of STN DBS in Moroccan Parkinsonian patients. Material and Methods: Thirty five patients underwent bilateral STN DBS from 2008 to 2016 in the Rabat University Hospital. Patients were assessed preoperatively and followed up for 6 to 12 months using the Unified Parkinson's Disease Rating Scale in four conditions (stimulation OFF and ON and medication OFF and ON), the levodopa-equivalent daily dose (LEDD), dyskinesia and fluctuation scores and PDQ39 scale for quality of life (QOL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30108543", "endSection": "abstract" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1552, "text": "The total K-SCOPA-AUT score showed a positive correlation with other non-motor symptoms [the Korean version of non-motor symptom scale (K-NMSS)], activities of daily living (Unified Parkinson's Disease Rating Scale part II) and quality of life [the Korean version of Parkinson's Disease Quality of Life 39 (K-PDQ39)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28122431", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 1147, "text": "METHODS: Static posturography (Centre of Pressure -CoP- parameters), gait (the Ten-Meter Walk Test [TMWT]), freezing of gait (the Freezing of Gait Questionnaire [FOG-Q]), the motor portion of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and patient-perceived quality of life (the 39-item Parkinson's disease Questionnaire [PDQ39]), were assessed at pre-test, post-test, and re-test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28290191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 647, "text": "The use of complementary and alternative medicine (CAM) therapy in nonmotor symptoms (NMS) for Parkinson disease (PD) is growing worldwide. Well-performed, systematic evidence-based research is largely lacking in this area and many studies include various forms of CAM with small patient numbers and a lack of standardization of the approaches studied. Taichi, Qigong, dance, yoga, mindfulness, acupuncture, and other CAM therapies are reviewed and there is some evidence for the following: Taichi in sleep and PDQ39; dance in cognition, apathy, and a mild trend to improved fatigue; yoga in PDQ39; and acupuncture in depression, PDQ39, and sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28805568", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 641, "text": "One hundred thirty patients with PD completed a booklet of questionnaires, which included the PDQ39 as a disease-specific measure of QoL, a symptom checklist, a mobility checklist, as well as patient ratings of disease stage and disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18543333", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1181, "text": "At 70% sensitivity, the specificity for PDQ39 score and PD Symptoms Questionnaire score for the prediction of parkinsonism was 73.1% and 80.1%, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035927", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 709, "text": "Workers completed a health status questionnaire (PDQ39) and a Parkinson disease (PD) Symptoms Questionnaire.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035927", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 917, "text": "As for specific questionnaires: the Parkinson`s Disease Questionnaire (PDQ-39) and the Parkinson's Disease Quality of Life Questionnaire (PDQL) have been described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23346238", "endSection": "abstract" }, { "offsetInBeginSection": 728, "offsetInEndSection": 841, "text": "HRQOL was assessed with the EuroQol-5D and the specific questionnaire Parkinson's Disease Questionnaire-39 items.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21163736", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 656, "text": "One hundred thirty patients with PD completed a booklet of questionnaires , which included the PDQ39 as a disease-specific measure of QoL , a symptom checklist , a mobility checklist , as well as patient ratings of disease stage and disability . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18543333", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 566, "text": "Here , we applied a novel diffusion-weighted imaging approach , diffusion MRI connectometry , to investigate the correlation of quality of life , evaluated by Parkinson 's Disease Questionnaire ( PDQ39 ) with the white matter structural connectivity in 27 non-demented PD patients ( disease duration of 5.3\u00a0\u00b1\u00a02.9\u00a0years , H and Y stage\u00a0=\u00a01.5\u00a0\u00b1\u00a00.6 , UPDRS-III\u00a0=\u00a013.7\u00a0\u00b1\u00a06.5 , indicating unilateral and mild motor involvement) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29542093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The psychometric properties of the Dutch version of the Parkinson 's disease questionnaire 39 ( PDQ39-DV ) were tested in 177 patients with Parkinson 's disease ( PD) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "This study explored whether reflexology could improve or sustain the wellbeing of people with Parkinosn's Disease [PD] using the PDQ39 wellbeing tool designed specifically for use with people with PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20347841", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 741, "text": "METHODS\nThe results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15778909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Evaluation of the Dutch version of the Parkinson's Disease Questionnaire 39.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702633", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The psychometric properties of the Dutch version of the Parkinson's disease questionnaire 39 (PDQ39-DV) were tested in 177 patients with Parkinson's disease (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17702633", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 737, "text": "METHODS: The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15778909", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 530, "text": "Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16258207", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 1150, "text": "METHODS: Static posturography (Centre of Pressure -CoP- parameters), gait (the Ten-Meter Walk Test [TMWT]), freezing of gait (the Freezing of Gait Questionnaire [FOG-Q]), the motor portion of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and patient-perceived quality of life (the 39-item Parkinson's disease Questionnaire [PDQ39]), were assessed at pre-test, post-test, and re-test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28290191", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 739, "text": "METHODS: The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15778909", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 815, "text": "Methods: A pilot study was conducted in which laptops were distributed to 50 patients for 1 year to see whether such a service was feasible (in terms of patient participation and compliance) and whether this intervention affected the patient's condition, measured in UPDRS, Mini-Mental Status Examination (MMSE), 39-item Parkinson's Disease Questionnaire (PDQ39), and H & Y Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30363378", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 843, "text": "They were assessed using the K-NMSS, the Unified Parkinson's Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinson's Disease Questionnaire 39 (PDQ39).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23323136", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 1003, "text": "Patients were also evaluated by using the Parkinson Disease Questionnaire -39 (PDQ39), the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28770096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "We investigated the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on quality of life (QOL) in patients with advanced Parkinson's disease, as self-assessed before and after surgery by completing the Parkinson's Disease Questionnaire (PDQ39).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16763974", "endSection": "abstract" } ] }, { "body": "Is palbociclib effective for glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30151703", "http://www.ncbi.nlm.nih.gov/pubmed/29726787" ], "ideal_answer": [ "No. In a clinical trial palbociclib monotherapy was not an effective treatment for recurrent glioblastoma." ], "exact_answer": "no", "type": "yesno", "id": "5e290a268b3851296d00000d", "snippets": [ { "offsetInBeginSection": 1543, "offsetInEndSection": 1810, "text": "Although further research is needed, cyclin-dependent kinase 4/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29726787", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1578, "text": "CONCLUSION: In this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30151703", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1584, "text": "CONCLUSION\n\nIn this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30151703", "endSection": "abstract" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1577, "text": "CONCLUSION In this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30151703", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1584, "text": "CONCLUSION\nIn this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30151703", "endSection": "abstract" } ] }, { "body": "List five proteins with antioxidant properties?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30387809", "http://www.ncbi.nlm.nih.gov/pubmed/29077914", "http://www.ncbi.nlm.nih.gov/pubmed/29577948" ], "ideal_answer": [ "thioredoxin 1 (Trx1), \nperoxiredoxin 1 (Prx1), \nGSH reductase (GSR),\nphosphatase and tensin homolog (PTEN)\nsuperoxide dismutase (SOD)" ], "exact_answer": [ [ "thioredoxin 1" ], [ "peroxiredoxin 1" ], [ "GSH reductase" ], [ "phosphatase and tensin homolog" ], [ "superoxide dismutase" ] ], "type": "list", "id": "5e482160d14c9f295d00000c", "snippets": [ { "offsetInBeginSection": 738, "offsetInEndSection": 974, "text": "Non\u2011reducing redox western blotting was performed to detect the redox status of intracellular antioxidant proteins, including thioredoxin 1 (Trx1), peroxiredoxin 1 (Prx1), GSH reductase (GSR), and phosphatase and tensin homolog (PTEN). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30387809", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 816, "text": "birds fed the ALA-supplemented diet had the highest plasma total antioxidant capacity (T-AOC) and superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) enzyme activities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29077914", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 891, "text": "on activation of Nrf2, the expressions of antioxidant responsive element (ARE)-dependent genes and proteins (GCLC, GCLM, GS, GR, GST, GPx, CAT, SOD, NQO1, HO-1) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29577948", "endSection": "abstract" } ] }, { "body": "Does the Mcm2-Ctf4-Pol\u03b1 axis play a role in transfer of histones to leading strand DNA at the replication forks?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30244834" ], "ideal_answer": [ "No, the Mcm2-Ctf4-Pola axis facilitates parental histone H3-H4 transfer to lagging strands." ], "exact_answer": "no", "type": "yesno", "id": "5e36d807b5b409ea5300000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The Mcm2-Ctf4-Pol\u03b1 Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30244834", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1045, "text": "Although essential for epigenetic inheritance, the transfer of parental histone (H3-H4)2 tetramers that contain epigenetic modifications to replicating DNA strands is poorly understood. Here, we show that the Mcm2-Ctf4-Pol\u03b1 axis facilitates the transfer of parental (H3-H4)2 tetramers to lagging-strand DNA at replication forks. Mutating the conserved histone-binding domain of the Mcm2 subunit of the CMG (Cdc45-MCM-GINS) DNA helicase, which translocates along the leading-strand template, results in a marked enrichment of parental (H3-H4)2 on leading strand, due to the impairment of the transfer of parental (H3-H4)2 to lagging strands. Similar effects are observed in Ctf4 and Pol\u03b1 primase mutants that disrupt the connection of the CMG helicase to Pol\u03b1 that resides on lagging-strand template. Our results support a model whereby parental (H3-H4)2 complexes displaced from nucleosomes by DNA unwinding at replication forks are transferred by the CMG-Ctf4-Pol\u03b1 complex to lagging-strand DNA for nucleosome assembly at the original location.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30244834", "endSection": "abstract" } ] }, { "body": "What is Scalp cirsoid aneurysms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12021881", "http://www.ncbi.nlm.nih.gov/pubmed/29864562", "http://www.ncbi.nlm.nih.gov/pubmed/22874530", "http://www.ncbi.nlm.nih.gov/pubmed/619442", "http://www.ncbi.nlm.nih.gov/pubmed/30295882", "http://www.ncbi.nlm.nih.gov/pubmed/21156709", "http://www.ncbi.nlm.nih.gov/pubmed/31384940", "http://www.ncbi.nlm.nih.gov/pubmed/8956889" ], "ideal_answer": [ "Cirsoid aneurysms are rare arteriovenous malformations of the scalp, which are usually of congenital etiology. They often present as an enlarging pulsatile scalp mass." ], "type": "summary", "id": "5e2b07537d50947c2f000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Scalp Arteriovenous Malformation (Cirsoid Aneurysm) in Adolescence: Report of 2 Cases and Review of the Literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29864562", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: Scalp arteriovenous malformations, also known as cirsoid aneurysms, are rare lesions that are congenital, traumatic, or postinfectious in nature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29864562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Cirsoid aneurysms, also known as scalp arteriovenous malformations (AVM), are rare congenital extracranial vascular anomalies that often present as an enlarging pulsatile scalp mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30295882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "OBJECTIVE: We report an interesting case of a right temporal pre-auricular arteriovenous fistula (cirsoid aneurysm) causing intractable tinnitus successfully managed by transarterial n-butyl cyanoacrylate glue embolisation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22874530", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cirsoid aneurysms are rare arteriovenous malformations of the scalp, which are usually of congenital etiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21156709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "BACKGROUND: Cirsoid aneurysms (arteriovenous fistulas) of the scalp are rare lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12021881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "BACKGROUND\n\nCirsoid aneurysms are uncommon arteriovenous fistulas of the scalp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8956889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "BACKGROUND\n\nCirsoid aneurysms (arteriovenous fistulas) of the scalp are rare lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12021881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "BACKGROUND Cirsoid aneurysms are uncommon arteriovenous fistulas of the scalp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8956889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "BACKGROUND Cirsoid aneurysms (arteriovenous fistulas) of the scalp are rare lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12021881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "BACKGROUND\nScalp cirsoid aneurysms are rare subcutaneous arteriovenous fistulae affecting the scalp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31384940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "The authors describe a case in which transcatheter embolization was used to treat a large arteriovenous malformation of the scalp (cirsoid aneurysm), with subsequent development of multiple aneurysms at the embolization sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/619442", "endSection": "abstract" } ] }, { "body": "Which gene is frequently involved in autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28769756", "http://www.ncbi.nlm.nih.gov/pubmed/26311780", "http://www.ncbi.nlm.nih.gov/pubmed/27854160", "http://www.ncbi.nlm.nih.gov/pubmed/19961535", "http://www.ncbi.nlm.nih.gov/pubmed/23676464", "http://www.ncbi.nlm.nih.gov/pubmed/21225301", "http://www.ncbi.nlm.nih.gov/pubmed/23261988", "http://www.ncbi.nlm.nih.gov/pubmed/26189928", "http://www.ncbi.nlm.nih.gov/pubmed/23649844", "http://www.ncbi.nlm.nih.gov/pubmed/30697589", "http://www.ncbi.nlm.nih.gov/pubmed/31143934", "http://www.ncbi.nlm.nih.gov/pubmed/25701871", "http://www.ncbi.nlm.nih.gov/pubmed/16951681", "http://www.ncbi.nlm.nih.gov/pubmed/30949481" ], "ideal_answer": [ "Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene." ], "exact_answer": [ "Lamin B1 gene", "LMNB1" ], "type": "factoid", "id": "5e355e20fbd6abf43b000065", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "An LMNB1 Duplication Caused Adult-Onset Autosomal Dominant Leukodystrophy in Chinese Family: Clinical Manifestations, Neuroradiology and Genetic Diagnosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769756", "endSection": "title" }, { "offsetInBeginSection": 187, "offsetInEndSection": 1258, "text": "Duplication or over expression of the lamin B1 (LMNB1) gene causes ADLD. In this study, we undertook a comprehensive clinical evaluation and genetic detection for a Chinese family with ADLD. The proband is a 52-year old man manifested with autonomic abnormalities, pyramidal tract dysfunction. MRI brain scan identified bilateral symmetric white matter (WM) hyper-intensities in periventricular and semi-oval WM, cerebral peduncles and middle cerebellar peduncles. The proband has a positive autosomal dominant family history with similar clinical manifestations with a trend of genetic anticipation. In order to understand the genetic cause of the disease in this family, target exome capture based next generation sequencing has been done, but no causative variants or possibly pathogenic variants has been identified. However, Multiplex ligand-dependent probe amplification (MLPA) showed whole duplication of LMNB1 gene which is co-segregated with the disease phenotype in this family. This is the first genetically confirmed LMNB1 associated ADLD pedigree from China.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 553, "text": "Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23649844", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 404, "text": "Duplication of the LMNB1 gene is the genetic cause of ADLD, yet the pathogenetic mechanism is not defined. In this study, we analysed cells and muscle tissue from three patients affected by ADLD, carrying an extra copy of the LMNB1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 449, "text": "Adult-onset autosomal-dominant leukodystrophy (ADLD) is a progressive and fatal neurological disorder characterized by early autonomic dysfunction, cognitive impairment, pyramidal tract and cerebellar dysfunction, and white matter loss in the central nervous system. ADLD is caused by duplication of the LMNB1 gene, which results in increased lamin B1 transcripts and protein expression. How duplication of LMNB1 leads to myelin defects is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23676464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Lamin B1 duplications cause autosomal dominant leukodystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951681", "endSection": "title" }, { "offsetInBeginSection": 531, "offsetInEndSection": 1457, "text": "ADLD is associated with duplications of the lamin B1 (LMNB1) gene but the mechanism by which the rearrangement conveys the phenotype is not fully defined. We analyzed four unrelated families segregating ADLD with autonomic symptoms for duplications of the LMNB1 gene. A single nucleotide polymorphism (SNP) array analysis revealed novel duplications spanning the entire LMNB1 gene in probands from each of the four families. We then analyzed the expression of lamin B1 in peripheral leukocytes by Western blot analysis in five patients from two available families. The protein levels of lamin B1 were found significantly increased. These results indicate that the ADLD phenotype associated with LMNB1 duplications is mediated by increased levels of the lamin B1 protein. Furthermore, we show that a molecular diagnosis for ADLD with autonomic symptoms can be obtained by a direct analysis of lamin B1 in peripheral leukocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21225301", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21225301", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Objective\n\nTo characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 ( __i_tag__ LMNB1 __end_i_tag__ ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30697589", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 259, "text": "Duplication or over expression of the lamin B1 (LMNB1) gene causes ADLD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Duplication and deletion upstream of __i_tag__ LMNB1 __end_i_tag__ in autosomal dominant adult-onset leukodystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30697589", "endSection": "title" }, { "offsetInBeginSection": 186, "offsetInEndSection": 330, "text": "We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26311780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30697589", "endSection": "title" }, { "offsetInBeginSection": 185, "offsetInEndSection": 329, "text": "We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26311780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "INTRODUCTION adult-onset autosomal dominant leukodystrophy (ADLD) is a rare inherited disorder due to a duplication of lamin-B1 (LMNB1) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26189928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23649844", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 209, "text": "To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 ( LMNB1 ).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30697589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Autosomal dominant leukodystrophy ( ADLD ) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 ( LMNB1 ) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23649844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Autosomal Dominant Leukodystrophy ( ADLD) , a fatal adult onset demyelinating disorder , is the only human disease that has been linked to mutations of the nuclear lamina protein , lamin B1 , and is primarily caused by duplications of the LMNB1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27854160", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 740, "text": "As a proof-of-concept , we studied autosomal dominant adult-onset demyelinating leukodystrophy ( ADLD ) due to lamin B1 ( LMNB1 ) duplication , a hereditary , progressive and fatal disorder affecting myelin in the CNS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31143934", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 323, "text": "We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy ( ADLD) , a fatal adult onset demyelinating disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26311780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Chromosomal rearrangements with duplication of the lamin B1 ( LMNB1 ) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy ( ADLD) , a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701871", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 267, "text": "Duplication or over expression of the lamin B1 ( LMNB1 ) gene causes ADLD . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701871", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 451, "text": "However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701871", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 1011, "text": "Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Autosomal Dominant Leukodystrophy (ADLD), a fatal adult onset demyelinating disorder, is the only human disease that has been linked to mutations of the nuclear lamina protein, lamin B1, and is primarily caused by duplications of the LMNB1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27854160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Objective To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30697589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "ABSTRACT Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23649844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "BACKGROUND AND PURPOSE: Duplications of lamin B1 (LMNB1) at 5q23 are implicated in adult-onset autosomal dominant leukodystrophy (ADLD) having been described in six families with diverse ethnic background but with a homogeneous phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19961535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "INTRODUCTION: adult-onset autosomal dominant leukodystrophy (ADLD) is a rare inherited disorder due to a duplication of lamin-B1 (LMNB1) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26189928", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 573, "text": "While at least a dozen disorders are associated with LMNA, the focus of this review is Autosomal Dominant Leukodystrophy (ADLD), the only disease associated with the lamin B1 gene (LMNB1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30949481", "endSection": "abstract" } ] }, { "body": "What is the radiation-induced CD8 lymphocyte apoptosis (RILA) assay used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30220974", "http://www.ncbi.nlm.nih.gov/pubmed/30327309" ], "ideal_answer": [ "Radiation-induced lymphocyte apoptosis (RILA) has been suggested as a predictive assay for adverse late reactions after radiotherapy." ], "exact_answer": [ "Radiation-induced lymphocyte apoptosis (RILA) has been suggested as a predictive assay for adverse late reactions after radiotherapy." ], "type": "factoid", "id": "5e48f2b6f8b2df0d49000005", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 142, "text": "Radiation-induced lymphocyte apoptosis (RILA) has been suggested as a predictive assay for adverse late reactions after radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30327309", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 298, "text": "We aimed toevaluate whether radiation-induced CD4 or CD8 T-lymphocyte apoptosis (RILA) correlates with the severity of radiation toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30220974", "endSection": "abstract" } ] }, { "body": "What are the puQTLs (promoter-usage Quantitative Trait Loci)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29116076" ], "ideal_answer": [ "The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains challenging. Regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs) have been mapped from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals. There are five categories of genes associated with puQTLs, distinguishing single from multi-promoter genes. Among multi-promoter genes, puQTL effects are either specific to a single promoter or to multiple promoters with variable effect orientations. Regulatory variants associated with opposite effects on different mRNA isoforms suggest compensatory mechanisms occurring between alternative promoters." ], "type": "summary", "id": "5e35cb27158f994d3a000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1183, "text": "The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains challenging. Here, we use natural genetic variation and CAGE transcriptomes from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals, to map 5376 and 110 regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs), respectively. We characterize five categories of genes associated with puQTLs, distinguishing single from multi-promoter genes. Among multi-promoter genes, we find puQTL effects either specific to a single promoter or to multiple promoters with variable effect orientations. Regulatory variants associated with opposite effects on different mRNA isoforms suggest compensatory mechanisms occurring between alternative promoters. Our analyses identify differential promoter usage and modulation of enhancer activity as molecular mechanisms underlying eQTLs related to regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29116076", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 610, "text": "Here, we use natural genetic variation and CAGE transcriptomes from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals, to map 5376 and 110 regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29116076", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 611, "text": "Here, we use natural genetic variation and CAGE transcriptomes from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals, to map 5376 and 110 regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29116076", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1487, "text": "Here, performing CAGE-seq on 154 lymphoblastoid cell lines, the authors map regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29116076", "endSection": "abstract" } ] }, { "body": "Which is the main epigenetic difference between poised and constitutive enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29932419", "http://www.ncbi.nlm.nih.gov/pubmed/26970625", "http://www.ncbi.nlm.nih.gov/pubmed/27285123", "http://www.ncbi.nlm.nih.gov/pubmed/27979994", "http://www.ncbi.nlm.nih.gov/pubmed/28275002", "http://www.ncbi.nlm.nih.gov/pubmed/21106759" ], "ideal_answer": [ "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.", "Histone H3K27ac separates active from poised enhancers and predicts developmental state.", ". The poised enhancer signature, involving H3K4me1 and low levels of H3K27ac, has been reported to mark inactive enhancers that are poised for future activation.. Histone H3K27ac separates active from poised enhancers and predicts developmental state.. We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.. These chromatin domains, mostly constitutive, may have been used as genomic niches where novel regulations could evolve due to both the preexistence of a structural backbone poised to integrate novel regulatory inputs, and a highly adaptive transcriptional readout. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and contributes to tumorigenesis in part by locally enhancing H3K27me3, and hence silencing of tumor suppressor genes", "Histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone." ], "exact_answer": [ "H3K27ac" ], "type": "factoid", "id": "5ca61f17ecadf2e73f000050", "snippets": [ { "offsetInBeginSection": 360, "offsetInEndSection": 677, "text": "Modifications of histones further lead to repressed, activated or poised gene transcription, thus bringing another level of fine tuning regulation of gene transcription. Embryonic Stem cells (ES cells) recapitulate within embryoid bodies (i.e., cell aggregates) or in 2D culture the early steps of cardiac development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27285123", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 1000, "text": " These chromatin domains, mostly constitutive, may have been used as genomic niches where novel regulations could evolve due to both the preexistence of a structural backbone poised to integrate novel regulatory inputs, and a highly adaptive transcriptional readout", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26970625", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 1006, "text": "These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and contributes to tumorigenesis in part by locally enhancing H3K27me3, and hence silencing of tumor suppressor genes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29932419", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 324, "text": "The poised enhancer signature, involving H3K4me1 and low levels of H3K27ac, has been reported to mark inactive enhancers that are poised for future activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27979994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Histone H3K27ac separates active from poised enhancers and predicts developmental state.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "title" }, { "offsetInBeginSection": 718, "offsetInEndSection": 842, "text": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "abstract" } ] }, { "body": "What is PRL3-zumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27699276" ], "ideal_answer": [ "PRL3-zumab is a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. PRL3-zumab specifically blocked PRL-3+, but not PRL-3-, orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3+ tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become \"extracellular oncotargets\" that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells.", "PRL3-zumab is a humanized monoclonal antibody specific for the epithelial-cell-associated phosphatase 3 (PRL-3) protein. It is approved for treatment of non-small cell lung carcinoma, adenocarcinoma of the stomach and gastroesophageal Junction, and recurrent glioblastoma." ], "type": "summary", "id": "5e2a0a02aa19d7443100000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "PRL3-zumab, a first-in-class humanized antibody for cancer therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27699276", "endSection": "title" }, { "offsetInBeginSection": 86, "offsetInEndSection": 442, "text": "Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated with shortened overall survival of GC patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27699276", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 1448, "text": "Using human GC cell lines, we demonstrated that PRL3-zumab specifically blocked PRL-3+, but not PRL-3-, orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3+ tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become \"extracellular oncotargets\" that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells. In summary, our results document a comprehensive cancer therapeutic approach to specific antibody-targeted therapy against the PRL-3 oncotarget as a case study for developing antibodies against other intracellular targets in drug discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27699276", "endSection": "abstract" } ] }, { "body": "Which receptor is inhibited by Tivozanib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29716948", "http://www.ncbi.nlm.nih.gov/pubmed/28287096", "http://www.ncbi.nlm.nih.gov/pubmed/23252559", "http://www.ncbi.nlm.nih.gov/pubmed/25908516", "http://www.ncbi.nlm.nih.gov/pubmed/28383032", "http://www.ncbi.nlm.nih.gov/pubmed/23818763", "http://www.ncbi.nlm.nih.gov/pubmed/25895472", "http://www.ncbi.nlm.nih.gov/pubmed/27771610", "http://www.ncbi.nlm.nih.gov/pubmed/28971328", "http://www.ncbi.nlm.nih.gov/pubmed/25591799", "http://www.ncbi.nlm.nih.gov/pubmed/24295377", "http://www.ncbi.nlm.nih.gov/pubmed/27128461", "http://www.ncbi.nlm.nih.gov/pubmed/29547835", "http://www.ncbi.nlm.nih.gov/pubmed/23013465", "http://www.ncbi.nlm.nih.gov/pubmed/24019545", "http://www.ncbi.nlm.nih.gov/pubmed/27853960", "http://www.ncbi.nlm.nih.gov/pubmed/30084668", "http://www.ncbi.nlm.nih.gov/pubmed/23701975", "http://www.ncbi.nlm.nih.gov/pubmed/23679664", "http://www.ncbi.nlm.nih.gov/pubmed/27128217", "http://www.ncbi.nlm.nih.gov/pubmed/21976547", "http://www.ncbi.nlm.nih.gov/pubmed/22493422" ], "ideal_answer": [ "Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3 tyrosine kinases." ], "exact_answer": [ "vascular endothelial growth factor receptors" ], "type": "factoid", "id": "5e2f0afcfbd6abf43b000028", "snippets": [ { "offsetInBeginSection": 1028, "offsetInEndSection": 1188, "text": "The addition of VEGF-R inhibitor Tivozanib to these systems abrogated the tension-induced paracrine effects on VECs and subsequently impaired BMSC osteogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29716948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND: Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2\u00a0and 3 tyrosine kinases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29547835", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 478, "text": "Tivozanib is a selective inhibitor of all three VEGFRs, with limited off-target interaction, which demonstrates efficacy with improved tolerability relative to multikinase VEGFR-TKIs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30084668", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 303, "text": "Tivozanib is a potent small molecule tyrosine kinase inhibitor against VEGFR1-3, with activity against PDGFR\u03b1/\u03b2 and cKIT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27771610", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 242, "text": "Tivozanib is an oral pan-VEGF receptor tyrosine kinase inhibitor that hits a central pathway in glioblastoma angiogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27853960", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 941, "text": "Tivozanib, a pan-inhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through induction of G2/M cell cycle arrest and apoptotic cell death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28383032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Tivozanib is a novel vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGF TKI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Tivozanib is a potent and selective inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23679664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Antiangiogenic effects of tivozanib, an oral VEGF receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23701975", "endSection": "title" }, { "offsetInBeginSection": 119, "offsetInEndSection": 241, "text": "Tivozanib is an oral pan-VEGF receptor tyrosine kinase inhibitor that hits a central pathway in glioblastoma angiogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27853960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "We investigated the effects of tivozanib, an oral vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization (CNV) in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23701975", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "PURPOSE\n\nTivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24019545", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 215, "text": "Tivozanib is a potent inhibitor of VEGF-1, -2 and -3 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295377", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1389, "text": "Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Tivozanib hydrochloride monohydrate (tivozanib; formerly KRN-951, AV-951) is a potent pan-VEGF receptor tyrosine kinase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23252559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Tivozanib hydrochloride monohydrate ( tivozanib; formerly KRN-951 , AV-951 ) is a potent pan-VEGF receptor tyrosine kinase inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23252559", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 368, "text": "Tivozanib is a potent , selective inhibitor of VEGF receptors 1 , 2 , and 3 , with a long half-life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27128217", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 213, "text": "Tivozanib is a potent inhibitor of VEGF-1 , -2 and -3 receptors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-1 ( VEGFR1) , -2 ( VEGFR2) , and -3 ( VEGFR3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25908516", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 267, "text": "Among other VEGF TKIs , tivozanib stands apart due to its selective kinase inhibitory properties as well as its high potency for inhibiting VEGF receptors 1 and 2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Tivozanib hydrochloride ( tivozanib ) is a potent , selective tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 , 2 , and 3 , with a long half-life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27128461", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 469, "text": "Tivozanib ( Fotivda ) is an oral , potent and highly selective vascular endothelial growth factor receptor ( VEGFR ) inhibitor that has been approved in the EU , Iceland and Norway for the first-line treatment of adult patients with advanced renal cell carcinoma ( RCC ) and for adult patients who are VEGFR and mammalian target of rapamycin ( mTOR ) pathway inhibitor-naive following disease progression after one prior treatment with cytokine therapy for advanced RCC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28971328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Tivozanib is a potent and highly specific orally available , tyrosine kinase inhibitor that targets vascular endothelial growth factor ( VEGF ) receptor-1 , VEGF receptor-2 , and VEGF receptor-3 at very low concentrations with a long half-life ( 4\u00a0days", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25895472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Tivozanib is a novel vascular endothelial growth factor receptor tyrosine kinase inhibitor ( VEGF TKI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Tivozanib hydrochloride ( tivozanib ) is a potent and selective tyrosine kinase inhibitor of all 3 vascular endothelial growth factor receptors with antitumor activity additive to 5-fluorouracil in preclinical models", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25591799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Tivozanib is a potent and highly specific orally available, tyrosine kinase inhibitor that targets vascular endothelial growth factor (VEGF) receptor-1, VEGF receptor-2, and VEGF receptor-3 at very low concentrations with a long half-life (4\u00a0days).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25895472", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 805, "text": "Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287096", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 227, "text": "Tivozanib is a potent inhibitor of VEGF-1, -2 and -3 receptors.MATERIALS &", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295377", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 359, "text": "Tivozanib is a potent, selective inhibitor of VEGF receptors 1, 2, and 3, with a long half-life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27128217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Tivozanib is a potent and highly specific orally available, tyrosine kinase inhibitor that targets vascular endothelial growth factor (VEGF) receptor-1, VEGF receptor-2, and VEGF receptor-3 at very low concentrations with a long half-life (4\u00a0days).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25895472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21976547", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "INTRODUCTION: Tivozanib is a novel tyrosine kinase inhibitor (TKI) which inhibits vascular endothelial growth factor (VEGF) receptors-1, -2, and -3 at nanomolar concentrations.AREAS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "PURPOSE: The antitumor activity and safety of tivozanib, which is a potent and selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, was assessed in patients with advanced/metastatic renal cell carcinoma (RCC).PATIENTS AND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22493422", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 980, "text": "Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287096", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 216, "text": "Tivozanib is a potent inhibitor of VEGF-1, -2 and -3 receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24295377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND: Tivozanib hydrochloride (tivozanib) is a potent and selective tyrosine kinase inhibitor of all 3 vascular endothelial growth factor receptors with antitumor activity additive to 5-fluorouracil in preclinical models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25591799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Introduction Tivozanib is a novel tyrosine kinase inhibitor (TKI) which inhibits vascular endothelial growth factor (VEGF) receptors-1, -2, and -3 at nanomolar concentrations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013465", "endSection": "abstract" }, { "offsetInBeginSection": 771, "offsetInEndSection": 940, "text": "Tivozanib, a pan-inhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through induction of G2/M cell cycle arrest and apoptotic cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28383032", "endSection": "abstract" } ] }, { "body": "Can discharge destinations be accurately predicted using the Risk Assessment and Prediction Tool (RAPT)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26305296", "http://www.ncbi.nlm.nih.gov/pubmed/24717404", "http://www.ncbi.nlm.nih.gov/pubmed/31327649", "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "http://www.ncbi.nlm.nih.gov/pubmed/29788192" ], "ideal_answer": [ "Yes. The Risk Assessment and Prediction Tool (RAPT) appears to be a valuable predictor of discharge destination after orthopedic surgery and neurosurgical procedures." ], "exact_answer": "yes", "type": "yesno", "id": "5e2b0d71fbd6abf43b000001", "snippets": [ { "offsetInBeginSection": 1380, "offsetInEndSection": 1640, "text": "CONCLUSION: Our analysis identified age, lower lumbar/lumbosacral surgery, and RAPT walk score as independent predictors of discharge to SNF, and demonstrated superior predictive power compared with the total RAPT Score when combined in a novel grading scale. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29788192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "PURPOSE: The aim of this study was to evaluate the value of conventional factors, the Risk Assessment and Predictor Tool (RAPT) and performance-based functional tests as predictors of delayed recovery after total hip arthroplasty (THA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305296", "endSection": "abstract" }, { "offsetInBeginSection": 1939, "offsetInEndSection": 2051, "text": "CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 2311, "offsetInEndSection": 2647, "text": "The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care. Additionally, it identifies intermediate-risk patients and could be used to implement targeted interventions to facilitate discharge home in this group of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1564, "text": "RESULTS: Overall predictive accuracy was 78%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "OBJECTIVE: To assess the relevance of the RAPT (Risk Assessment and Prediction Tool), among a cohort of patients undergoing total hip arthroplasty (THA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24717404", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1369, "text": "CONCLUSION: This study confirmed the usefulness of the RAPT to help in patient orientation decision after total hip arthroplasty. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24717404", "endSection": "abstract" }, { "offsetInBeginSection": 1947, "offsetInEndSection": 2058, "text": "CONCLUSIONS\n\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1690, "text": "RAPT scores<6 and >10 (of 12) predicted with >90% accuracy discharge to inpatient rehabilitation and home, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 2319, "offsetInEndSection": 2490, "text": "The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 466, "text": "The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 1939, "offsetInEndSection": 2049, "text": "CONCLUSIONS The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 467, "text": "The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 773, "text": "A low RAPT score is reported to indicate a high risk of needing any form of inpatient rehabilitation after TJA, including short-term nursing facilities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 1947, "offsetInEndSection": 2058, "text": "CONCLUSIONS\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 1887, "offsetInEndSection": 1998, "text": "CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: The Risk Assessment and Prediction Tool (RAPT) is used to predict patient discharge disposition after total joint arthroplasty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31327649", "endSection": "abstract" }, { "offsetInBeginSection": 1943, "offsetInEndSection": 2054, "text": "CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106801", "endSection": "abstract" } ] }, { "body": "What is Perturb-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27984732" ], "ideal_answer": [ "Perturb-seq is a technique that combines single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool. Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individual perturbations and their genetic interactions. By decomposing many high content measurements into the effects of perturbations, their interactions, and diverse cell metadata, Perturb-seq dramatically increases the scope of pooled genomic assays." ], "type": "summary", "id": "5e35c4ea9be68b5512000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27984732", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1056, "text": "Genetic screens help infer gene function in mammalian cells, but it has remained difficult to assay complex phenotypes-such as transcriptional profiles-at scale. Here, we develop Perturb-seq, combining single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool. We demonstrate Perturb-seq by analyzing 200,000 cells in immune cells and cell lines, focusing on transcription factors regulating the response of dendritic cells to lipopolysaccharide (LPS). Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individual perturbations and\u00a0their genetic interactions. We posit new functions for regulators of differentiation, the anti-viral response, and mitochondrial function during immune activation. By decomposing many high content measurements into the effects of perturbations, their interactions, and diverse cell metadata, Perturb-seq dramatically increases the scope of pooled genomic assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27984732", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 368, "text": "Here, we develop Perturb-seq, combining single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27984732", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 369, "text": "Here, we develop Perturb-seq, combining single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27984732", "endSection": "abstract" } ] }, { "body": "What is the content of the REPAIRtoire database?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21051355" ], "ideal_answer": [ "The REPAIRtoire database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases correlated with mutations in genes encoding DNA repair proteins. REPAIRtoire provides also links to publications and external databases." ], "type": "summary", "id": "5e490d276d0a277941000001", "snippets": [ { "offsetInBeginSection": 102, "offsetInEndSection": 549, "text": " The database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases correlated with mutations in genes encoding DNA repair proteins. REPAIRtoire provides also links to publications and external databases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21051355", "endSection": "abstract" } ] }, { "body": "Has amantadine ER been approved by the FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29532440" ], "ideal_answer": [ "Yes, amantadine ER is an US FDA-approved treatment." ], "exact_answer": "yes", "type": "yesno", "id": "5e2db15cfbd6abf43b000014", "snippets": [ { "offsetInBeginSection": 270, "offsetInEndSection": 404, "text": "ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRITM) is a recent US FDA-approved treatment for dyskinesia in PD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29532440", "endSection": "abstract" } ] }, { "body": "Can PRL3-zumab inhibit PRL3+ cancer cells in vitro and in vivo?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31171773" ], "ideal_answer": [ "PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro." ], "exact_answer": "no", "type": "yesno", "id": "5e2a0eb1aa19d7443100000c", "snippets": [ { "offsetInBeginSection": 236, "offsetInEndSection": 332, "text": "Here we show that PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171773", "endSection": "abstract" } ] }, { "body": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25808775", "http://www.ncbi.nlm.nih.gov/pubmed/30442398", "http://www.ncbi.nlm.nih.gov/pubmed/30345741", "http://www.ncbi.nlm.nih.gov/pubmed/19410375", "http://www.ncbi.nlm.nih.gov/pubmed/20155985" ], "ideal_answer": [ "Circulating tumour cells (CTCs) are significantly rare entity in the blood of patients with non-small cell lung cancer (NSCLC) patients as well as in other types of cancer. Small-cell lung cancer cells are typically quiescent, whereas CTCs can be up-regulated in response to radiation or chemical agents and may contribute to tumorigenesis as an endogenous red cell marker.", "extremely low", "However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge.", "However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. However, selective capture and quantification of CTCs from whole blood was still full of challenge due to the extremely scare number of CTCs.", "We have focused on breast cancer as most clinical studies on CTC detection so far have been done in these patients. However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge.", "CTCs are of extremely low number (as low as 1 in 10(9) hematologic cells) in the blood of patients.", "However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. This study reports a microfluidic-based optical sensing device for label-free detection of circulating tumor cells (CTCs), a rare cell species in blood circulation." ], "exact_answer": [ "1 in 10 to 9th", "1e-9", "1 in 10^9" ], "type": "factoid", "id": "5c7a4fddd774d04240000009", "snippets": [ { "offsetInBeginSection": 882, "offsetInEndSection": 997, "text": "We have focused on breast cancer as most clinical studies on CTC detection so far have been done in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19410375", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 370, "text": "However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20155985", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 255, "text": "However, selective capture and quantification of CTCs from whole blood was still full of challenge due to the extremely scare number of CTCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30345741", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1564, "text": "Finally, the IMNs were successfully applied to the isolation and detection of CTCs in cancer patient peripheral blood samples and as low as one CTC in the whole blood was captured and identified by the ICC method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30442398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "This study reports a microfluidic-based optical sensing device for label-free detection of circulating tumor cells (CTCs), a rare cell species in blood circulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25808775", "endSection": "abstract" } ] }, { "body": "What is gamma sterilization used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19610053", "http://www.ncbi.nlm.nih.gov/pubmed/24737302", "http://www.ncbi.nlm.nih.gov/pubmed/26498171", "http://www.ncbi.nlm.nih.gov/pubmed/24119926" ], "ideal_answer": [ "Gamma sterilization of bone allografts is used as a gold standard method to provide safety against disease transmission. Also, gamma (g)-sterilization has been commonly employed for wide range of products as indicated by the pharmacopoeias." ], "type": "summary", "id": "5e48f90bf8b2df0d49000006", "snippets": [ { "offsetInBeginSection": 162, "offsetInEndSection": 276, "text": "Gamma (\u03b3)-sterilization has been commonly employed for wide range of products as indicated by the pharmacopoeias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26498171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Gamma sterilization is usually used to minimize the risk of infection transmission through bone allografts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Gamma sterilization of bone allografts is used as a gold standard method to provide safety against disease transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24737302", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1124, "text": "It was determined that gamma sterilization was the preferred sterilization method of choice for this device. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19610053", "endSection": "abstract" } ] }, { "body": "Does Estrogen lead to forkhead FoxA1 activation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22713214", "http://www.ncbi.nlm.nih.gov/pubmed/27883218", "http://www.ncbi.nlm.nih.gov/pubmed/21151129", "http://www.ncbi.nlm.nih.gov/pubmed/16009131", "http://www.ncbi.nlm.nih.gov/pubmed/25707489", "http://www.ncbi.nlm.nih.gov/pubmed/16087863", "http://www.ncbi.nlm.nih.gov/pubmed/20610384", "http://www.ncbi.nlm.nih.gov/pubmed/23771556" ], "ideal_answer": [ "The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA.", "We showed that CTCF acts upstream of the \"pioneer\" factor FOXA1 in determining the genomic response to estrogen.", "The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA", "Yes, estrogen-induced transcriptional activation of FoxA1 is tightly regulated by estrogen receptor tyrosine kinase and enhances Forkhead protein expression.", "Yes, induction of forkhead FoxA1 activation by estrogen seems to result in increased expression of the ERK2/ERK1 pathway in breast cancer cells. (PMID: 21494614) We also find that the testis-specific variant of the FOXA1 gene, which encodes the triggering receptor encoded by exon 9 on estrogen, is recruited to kinetochores and contributes to estrogen-induced silencing of NF-kappaB activation at the mating-type locus. ( PMID: 20160027)" ], "exact_answer": "yes", "type": "yesno", "id": "5ca61b14ecadf2e73f00004f", "snippets": [ { "offsetInBeginSection": 682, "offsetInEndSection": 795, "text": "We showed that CTCF acts upstream of the \"pioneer\" factor FOXA1 in determining the genomic response to estrogen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20610384", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 448, "text": "Almost all ER-chromatin interactions and gene expression changes depended on the presence of FOXA1 and FOXA1 influenced genome-wide chromatin accessibility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "FOXA1 is a key determinant of estrogen receptor function and endocrine response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151129", "endSection": "title" }, { "offsetInBeginSection": 830, "offsetInEndSection": 938, "text": "As such, FOXA1 is a major determinant of estrogen-ER activity and endocrine response in breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151129", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 139, "text": "Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16087863", "endSection": "title" }, { "offsetInBeginSection": 826, "offsetInEndSection": 1044, "text": "Furthermore, knockdown of FoxA1 expression blocks the association of ER with chromatin and estrogen-induced gene expression demonstrating the necessity of FoxA1 in mediating an estrogen response in breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16009131", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 94, "text": "FoxA1 determines estrogen receptor action in breast cancer progression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713214", "endSection": "title" }, { "offsetInBeginSection": 737, "offsetInEndSection": 852, "text": "Given previous findings from cell lines, FoxA1 appears to play a critical role in this reprogramming of ER binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713214", "endSection": "abstract" }, { "offsetInBeginSection": 1508, "offsetInEndSection": 1606, "text": "FOXA1 expression can independently predict chemosensitivity of ER-positive breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25707489", "endSection": "abstract" }, { "offsetInBeginSection": 1601, "offsetInEndSection": 1677, "text": " FOXA1 expression could be a prognostic marker in ER-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23771556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27883218", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 806, "text": " The phosphomimetic FoxA1 promoted the activation of estrogen signaling, whereas the nonphosphorylatable FoxA1 suppressed its activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27883218", "endSection": "abstract" } ] }, { "body": "What is detected by the UV-damaged DNA-binding protein (UV-DDB) complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12034848", "http://www.ncbi.nlm.nih.gov/pubmed/12812979", "http://www.ncbi.nlm.nih.gov/pubmed/16473935" ], "ideal_answer": [ "Upon UV irradiation of primate cells, UV-DDB associates tightly with chromatin and is involved in global genomic nucleotide excision repair (NER) in mammalian cells." ], "exact_answer": [ "UV-DDB associates tightly with chromatin and is involved in global genomic nucleotide excision repair (NER)" ], "type": "factoid", "id": "5e46da9c3f5415952900000a", "snippets": [ { "offsetInBeginSection": 213, "offsetInEndSection": 308, "text": "UV-damaged DNA-binding protein complex (UV-DDB), involved in the damage recognition step of NER", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16473935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The UV-damaged DNA binding protein complex (UV-DDB) is implicated in global genomic nucleotide excision repair (NER) in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12034848", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 394, "text": "Upon UV irradiation of primate cells, UV-DDB associates tightly with chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12034848", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 516, "text": " The cells of some XP-E patients are deficient in a protein complex (consisting of two subunits: p127/DDBI and p48/DDB2) which binds to UV-damaged DNA (UV-DDB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12812979", "endSection": "abstract" } ] }, { "body": "What is the current regulation of eye lens radiation exposure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29687260", "http://www.ncbi.nlm.nih.gov/pubmed/29155416", "http://www.ncbi.nlm.nih.gov/pubmed/30053275" ], "ideal_answer": [ "The reduction of the dose limit for eye lens from 150 to 20 mSv yr-1 must be implemented by EU member states by February 2018. Consequently, there is a requirement for all employers engaged with work with ionising radiation to have appropriate monitoring arrangements in place by this date to demonstrate that they can meet this new limit for all workers. Eye lens dose is conventionally monitored by specific dosemeters worn near the eye.\nThe yearly ocular lens dose, particularly for interventionists dealing with complex interventions, could cross the permitted yearly limit set by the new Euratom directive. Therefore, X-ray safety glasses would become mandatory for complex radiological vascular interventions." ], "type": "summary", "id": "5e4981e96d0a277941000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 438, "text": "The reduction of the dose limit for eye lens from 150 to 20 mSv yr-1 must be implemented by EU member states by February 2018. Consequently, there is a requirement for all employers engaged with work with ionising radiation to have appropriate monitoring arrangements in place by this date to demonstrate that they can meet this new limit for all workers. Eye lens dose is conventionally monitored by specific dosemeters worn near the eye", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155416", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 897, "text": "Doses to the whole body may be used as an indicator of the eye lens doses in the monitored department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Staff at nuclear medicine departments receive doses of ionising radiation higher than the staff of radiotherapy and radiology departments, with the exception of interventional radiologists", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053275", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 284, "text": "The annual permissible radiation ocular lens dose has been reduced to 20 millisieverts (mSv) in the current European directive 2013/59/Euratom. The aim of this study was to evaluate the personal radiation dose for vascular interventions with special focus on ocular lens dose", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29687260", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1656, "text": "The yearly ocular lens dose, particularly for interventionists dealing with complex interventions, could cross the permitted yearly limit set by the new Euratom directive. Therefore, X-ray safety glasses would become mandatory for complex radiological vascular interventions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29687260", "endSection": "abstract" }, { "offsetInBeginSection": 1457, "offsetInEndSection": 1614, "text": "'for the nuclear industry and other non-medical sectors the use of a whole body dosimeter is considered likely to be sufficient for the majority of workers'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29155416", "endSection": "abstract" } ] }, { "body": "Does association with the nuclear pore promote gene silencing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17724121", "http://www.ncbi.nlm.nih.gov/pubmed/28039207", "http://www.ncbi.nlm.nih.gov/pubmed/20407419", "http://www.ncbi.nlm.nih.gov/pubmed/21811608", "http://www.ncbi.nlm.nih.gov/pubmed/12802065" ], "ideal_answer": [ "MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. The nucleoporin Nup358 plays an important role in this process" ], "exact_answer": "yes", "type": "yesno", "id": "5cc011e2a49efeb44c000001", "snippets": [ { "offsetInBeginSection": 244, "offsetInEndSection": 542, "text": "Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28039207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28039207", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 621, "text": "To assess Tpr's role as an architectural element of the NPC, we have studied the sequential disassembly and reassembly of NPCs in mitotic cells, paralleled by studies of cells depleted of Tpr as a result of posttranscriptional tpr gene silencing by RNA interference (RNAi).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12802065", "endSection": "abstract" }, { "offsetInBeginSection": 945, "offsetInEndSection": 1091, "text": "The results raise the possibility that NPC-localized protein desumoylation may be a key regulatory event preventing inappropriate pre-mRNA export.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17724121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21811608", "endSection": "title" } ] }, { "body": "Which methods are used for genome segmentation of gene expression data?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17358192", "http://www.ncbi.nlm.nih.gov/pubmed/23077526", "http://www.ncbi.nlm.nih.gov/pubmed/12386005" ], "ideal_answer": [ "Most of the used methods are variations of Markov Models such as Markov Chain Monte Carlo (MCMC) or Combinatorial methods.", "We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome.", "We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome. We introduce Markov models for segmentation of symbolic sequences, extending a segmentation procedure based on the Jensen-Shannon divergence that has been introduced earlier. Our method is based on a combinatorial genome segmentation solely using information on combinations of epigenetic marks.", ". We introduce Markov models for segmentation of symbolic sequences, extending a segmentation procedure based on the Jensen-Shannon divergence that has been introduced earlier.. Our method is based on a combinatorial genome segmentation solely using information on combinations of epigenetic marks.. We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome.", "reversible jump markov chain monte carlo (rjmcmc) method", "We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome. We introduce Markov models for segmentation of symbolic sequences, extending a segmentation procedure based on the Jensen-Shannon divergence that has been introduced earlier." ], "exact_answer": [ [ "Reversible Jump Markov Chain Monte Carlo", "RJMCMC" ], [ "Markov Models" ], [ "combinatorial genome segmentation" ] ], "type": "list", "id": "5c72c9207c78d6947100007b", "snippets": [ { "offsetInBeginSection": 256, "offsetInEndSection": 500, "text": "We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12386005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "We introduce Markov models for segmentation of symbolic sequences, extending a segmentation procedure based on the Jensen-Shannon divergence that has been introduced earlier. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17358192", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 494, "text": "Our method is based on a combinatorial genome segmentation solely using information on combinations of epigenetic marks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077526", "endSection": "abstract" } ] }, { "body": "Which receptor is inhibited by Teprotumumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28427155", "http://www.ncbi.nlm.nih.gov/pubmed/26287404", "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "http://www.ncbi.nlm.nih.gov/pubmed/29273685", "http://www.ncbi.nlm.nih.gov/pubmed/30575804", "http://www.ncbi.nlm.nih.gov/pubmed/28467880", "http://www.ncbi.nlm.nih.gov/pubmed/29744034", "http://www.ncbi.nlm.nih.gov/pubmed/30215690", "http://www.ncbi.nlm.nih.gov/pubmed/27346786", "http://www.ncbi.nlm.nih.gov/pubmed/29847668", "http://www.ncbi.nlm.nih.gov/pubmed/25105999" ], "ideal_answer": [ "Teprotumumab is a monoclonal inhibitory antibody targeting IGF-1 receptor." ], "exact_answer": [ "IGF-1" ], "type": "factoid", "id": "5e2902688b3851296d000005", "snippets": [ { "offsetInBeginSection": 1366, "offsetInEndSection": 1568, "text": "A recently completed therapeutic trial of teprotumumab, a human IGF1R inhibiting antibody, in patients with moderate to severe, active TAO, indicates the potential effectiveness and safety of the drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29273685", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1130, "text": "Results from a very recently published clinical trial assessing the safety and efficacy of teprotumumab, an inhibitory human anti-IGF-IR monoclonal antibody, in active, moderate to severe TAO are extremely encouraging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29744034", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 829, "text": "The induction in fibrocytes is a consequence of increased TNF-\u03b1 gene promoter activity and is independent of ongoing protein synthesis. It could be attenuated by dexamethasone and the IGF-1 receptor inhibiting antibody, teprotumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29847668", "endSection": "abstract" }, { "offsetInBeginSection": 1384, "offsetInEndSection": 1558, "text": "These observations served as the rationale for implementing a recently completed therapeutic trial of teprotumumab, a monoclonal inhibitory antibody targeting IGF-IR in TAO. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30215690", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1599, "text": "Results of randomised controlled trials investigating the efficacy of the IGF-1 receptor antibody teprotumumab and the interleukin-6 receptor antibody tocilizumab are expected shortly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27346786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28427155", "endSection": "title" }, { "offsetInBeginSection": 418, "offsetInEndSection": 670, "text": "METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "TSH-Mediated TNF\u03b1 Production in Human Fibrocytes Is Inhibited by Teprotumumab, an IGF-1R Antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "endSection": "title" }, { "offsetInBeginSection": 561, "offsetInEndSection": 704, "text": "Teprotumumab (TMB) is a human monoclonal IGF-1R blocking antibody currently in clinical trial for GO and inhibits TSHR-mediated actions in FCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1272, "text": "CONCLUSIONS Teprotumumab attenuates the actions of both IGF-1 and TSH in fibrocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1 action in fibrocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "title" }, { "offsetInBeginSection": 612, "offsetInEndSection": 705, "text": "DESIGN Fibrocytes were treated without or with teprotumumab in combination with IGF-1 or TSH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30575804", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "TSH-Mediated TNF\u03b1 Production in Human Fibrocytes Is Inhibited by Teprotumumab , an IGF-1R Antagonist", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "endSection": "title" }, { "offsetInBeginSection": 568, "offsetInEndSection": 712, "text": "Teprotumumab ( TMB ) is a human monoclonal IGF-1R blocking antibody currently in clinical trial for GO and inhibits TSHR-mediated actions in FCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 704, "text": "Teprotumumab (TMB) is a human monoclonal IGF-1R blocking antibody currently in clinical trial for GO and inhibits TSHR-mediated actions in FCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 676, "text": "Teprotumumab, a monoclonal IGF-1R antagonist, has demonstrated previously in a 24 week, randomized, controlled trial to produce significant changes in composite outcomes of proptosis and clinical activity score as compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30575804", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 671, "text": "METHODS\nWe conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467880", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 506, "text": "Teprotumumab (RV 001, R1507) is a human monoclonal anti-IGF-1R blocking antibody currently undergoing a phase 2 clinical trial in patients with active TAO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 835, "text": "The most promising results are observed with small thyroid stimulating hormone receptor molecules interacting with the receptor on thyrocytes and fibroblasts and with the anti-IGF-1 receptor antibody teprotumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105999", "endSection": "abstract" }, { "offsetInBeginSection": 1240, "offsetInEndSection": 1355, "text": "The induction could be attenuated by dexamethasone and by IGF-I receptor-blocking antibodies, teprotumumab and 1H7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26287404", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 506, "text": "Teprotumumab (RV 001, R1507) is a human monoclonal anti-IGF-1R blocking antibody currently undergoing a phase 2 clinical trial in patients with active TAO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 836, "text": "The most promising results are observed with small thyroid stimulating hormone receptor molecules interacting with the receptor on thyrocytes and fibroblasts and with the anti-IGF-1 receptor antibody teprotumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105999", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 675, "text": "Teprotumumab, a monoclonal IGF-1R antagonist, has demonstrated previously in a 24 week, randomized, controlled trial to produce significant changes in composite outcomes of proptosis and clinical activity score as compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30575804", "endSection": "abstract" } ] }, { "body": "What is the cause of the disease Xeroderma Pigmentosum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28974143", "http://www.ncbi.nlm.nih.gov/pubmed/29403087", "http://www.ncbi.nlm.nih.gov/pubmed/26074087", "http://www.ncbi.nlm.nih.gov/pubmed/29105242", "http://www.ncbi.nlm.nih.gov/pubmed/28676261" ], "ideal_answer": [ "Mutations in the ERCC1 or ERCC4 genes cause a remarkable array of rare inherited human disorders including specific forms of xeroderma pigmentosum. Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration." ], "exact_answer": [ "Defective NER, such as mutated ERCC1 or ERCC$ genes" ], "type": "factoid", "id": "5e46e74e3f5415952900000b", "snippets": [ { "offsetInBeginSection": 172, "offsetInEndSection": 449, "text": "ERCC4 (XPF) encodes a protein that forms a complex with ERCC1 and is required for the 5' incision during nucleotide excision repair. ERCC4 is also FANCQ, illustrating a critical role in interstrand crosslink repair. Pathogenic variants in this gene cause xeroderma pigmentosum,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29105242", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 364, "text": " ERCC4 mutations have been known to cause xeroderma pigmentosum complementation group F (XP-F)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403087", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 301, "text": "Any mutations in XPA cause classical Xeroderma pigmentosum disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28974143", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 561, "text": " Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676261", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1314, "text": "mutations in the ERCC1 or ERCC4 genes cause a remarkable array of rare inherited human disorders. These include specific forms of xeroderma pigmentosum,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26074087", "endSection": "abstract" } ] }, { "body": "List Alkaptonuria Triad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18846913", "http://www.ncbi.nlm.nih.gov/pubmed/27142149", "http://www.ncbi.nlm.nih.gov/pubmed/21772695", "http://www.ncbi.nlm.nih.gov/pubmed/21927854", "http://www.ncbi.nlm.nih.gov/pubmed/31022456", "http://www.ncbi.nlm.nih.gov/pubmed/29501639", "http://www.ncbi.nlm.nih.gov/pubmed/23105706", "http://www.ncbi.nlm.nih.gov/pubmed/26474772", "http://www.ncbi.nlm.nih.gov/pubmed/21254745" ], "ideal_answer": [ "Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria, ochronosis, and arthritis." ], "exact_answer": [ [ "homogentisic aciduria" ], [ "ochronosis" ], [ "arthritis" ] ], "type": "list", "id": "5e2f972bfbd6abf43b000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Cardiac ochronosis is a rare complication of alkaptonuria, a disorder of tyrosine metabolism characterized by a triad of dark urine, pigmentation of tissues, and ochronotic arthropathies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501639", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 726, "text": "The condition is characterised by a clinical triad of symptoms; homogentisic aciduria from birth, ochronosis (darkening) of collagenous tissues (from \u223c30years of age) and ochronotic osteoarthropathy in weight bearing joints due to long term ochronosis in them (from \u223c40years of age). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27142149", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 264, "text": " The condition has a triad of clinical features, the most damaging of which is ochronotic osteoarthropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26474772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria, ochronosis, and arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21772695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Alkaptonuria (AKU) is an autosomal recessive disorder due to homogentisate 1,2-dioxygenase (HGD) deficiency in the liver and characterized by a triad of signs, according to chronology of appearance: homogentisic aciduria (HGA) or alkaptonuria, ochronosis then ochronotic arthropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21927854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria (dark urine), relentlessly progressive arthritis and ochronosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18846913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Alkaptonuria, a metabolic disorder characterized by a triad of homogentisic aciduria, arthritis and ochronosis is one of the first conditions in the charter of group of inborn errors of metabolism proposed to have Mendelian recessive inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23105706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria, ochronosis, and arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21772695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Cardiac ochronosis is a rare complication of alkaptonuria, a disorder of tyrosine metabolism characterized by a triad of dark urine, pigmentation of tissues, and ochronotic arthropathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Alkaptonuria ( AKU ) is an autosomal recessive disorder due to homogentisate 1,2-dioxygenase ( HGD ) deficiency in the liver and characterized by a triad of signs , according to chronology of appearance: homogentisic aciduria ( HGA ) or alkaptonuria , ochronosis then ochronotic arthropathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21927854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Alkaptonuria , a metabolic disorder characterized by a triad of homogentisic aciduria , arthritis and ochronosis is one of the first conditions in the charter of group of inborn errors of metabolism proposed to have Mendelian recessive inheritance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23105706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Cardiac ochronosis is a rare complication of alkaptonuria , a disorder of tyrosine metabolism characterized by a triad of dark urine , pigmentation of tissues , and ochronotic arthropathies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria ( dark urine) , relentlessly progressive arthritis and ochronosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18846913", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 734, "text": "The condition is characterised by a clinical triad of symptoms; homogentisic aciduria from birth , ochronosis ( darkening ) of collagenous tissues ( from \u223c30years of age ) and ochronotic osteoarthropathy in weight bearing joints due to long term ochronosis in them ( from \u223c40years of age", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27142149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria , ochronosis , and arthritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21772695", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 475, "text": "This causes the classic clinical triad: ( 1 ) homogentisic aciduria ( urine blackens on standing when oxidized or alkalinized); ( 2 ) eumelanin-like pigmentation of skin , sclera , cartilages , etc and ( 3 ) degenerative ochronic arthropathies usually in the fourth decade of life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21254745", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 337, "text": "It presents with a clinical triad of features; HGA in urine , ochronosis of collagenous tissues , and the subsequent ochronotic arthritis of these tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31022456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria (dark urine), relentlessly progressive arthritis and ochronosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18846913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria, ochronosis, and arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21772695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Alkaptonuria, a metabolic disorder characterized by a triad of homogentisic aciduria, arthritis and ochronosis is one of the first conditions in the charter of group of inborn errors of metabolism proposed to have Mendelian recessive inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23105706", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 466, "text": "This causes the classic clinical triad: (1) homogentisic aciduria (urine blackens on standing when oxidized or alkalinized); (2) eumelanin-like pigmentation of skin, sclera, cartilages, etc and (3) degenerative ochronic arthropathies usually in the fourth decade of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21254745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Alkaptonuria (AKU) is an autosomal recessive disorder due to homogentisate 1,2-dioxygenase (HGD) deficiency in the liver and characterized by a triad of signs, according to chronology of appearance: homogentisic aciduria (HGA) or alkaptonuria, ochronosis then ochronotic arthropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21927854", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 465, "text": "This causes the classic clinical triad: (1) homogentisic aciduria (urine blackens on standing when oxidized or alkalinized); (2) eumelanin-like pigmentation of skin, sclera, cartilages, etc and (3) degenerative ochronic arthropathies usually in the fourth decade of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21254745", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 725, "text": "The condition is characterised by a clinical triad of symptoms; homogentisic aciduria from birth, ochronosis (darkening) of collagenous tissues (from \u223c30years of age) and ochronotic osteoarthropathy in weight bearing joints due to long term ochronosis in them (from \u223c40years of age).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27142149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Alkaptonuria (AKU) is an autosomal recessive disorder due to homogentisate 1,2-dioxygenase (HGD) deficiency in the liver and characterized by a triad of signs, according to chronology of appearance: homogentisic aciduria (HGA) or alkaptonuria, ochronosis then ochronotic arthropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21927854", "endSection": "abstract" } ] }, { "body": "Can LB-100 sensitize ovarian carcinoma to cisplatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25376608" ], "ideal_answer": [ "Yes, LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity." ], "exact_answer": "yes", "type": "yesno", "id": "5e29f959aa19d74431000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376608", "endSection": "title" }, { "offsetInBeginSection": 817, "offsetInEndSection": 892, "text": "LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376608", "endSection": "abstract" }, { "offsetInBeginSection": 1499, "offsetInEndSection": 1666, "text": "Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376608", "endSection": "abstract" } ] }, { "body": "List T-UCRs that have been implicated in breast cancer", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29312798", "http://www.ncbi.nlm.nih.gov/pubmed/27447964" ], "ideal_answer": [ "Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no protein-coding capacity. Transcribed ultraconserved regions (T-UCRs) are a type of lncRNA and are conserved among human, chick, dog, mouse and rat genomes. These sequences are involved in cancer biology and tumourigenesis. Overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients. Uc.38 negatively regulates the expression of the pre-B-cell leukaemia homeobox 1 (PBX1) protein and subsequently affects the expression of Bcl-2 family members, ultimately inducing breast cancer cell apoptosis." ], "exact_answer": [ [ "uc.63" ], [ "uc.38" ] ], "type": "list", "id": "5e369ecfb5b409ea53000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Ultraconserved long non-coding RNA uc.63 in breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447964", "endSection": "title" }, { "offsetInBeginSection": 376, "offsetInEndSection": 1008, "text": "We found that overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients. uc.63 is localized in the third intron of exportin-1 gene (XPO1) and is transcribed in the same orientation of its host gene. Interestingly, silencing of uc.63 induces apoptosis in vitro. However, silencing of host gene XPO1 does not cause the same effect suggesting that the transcription of uc.63 is independent of XPO1. Our results reveal an important role of uc.63 in promoting breast cancer cells survival and offer the prospect to identify a signature associated with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "uc.38 induces breast cancer cell apoptosis via PBX1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29312798", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1287, "text": "Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no protein-coding capacity. Transcribed ultraconserved regions (T-UCRs) are a type of lncRNA and are conserved among human, chick, dog, mouse and rat genomes. These sequences are involved in cancer biology and tumourigenesis. Nevertheless, the clinical significance and biological mechanism of T-UCRs in breast cancer remain largely unknown. The expression of uc.38, a T-UCR, was down-regulated in both breast cancer tissues and breast cancer cell lines. However, uc.38 was expressed at significantly lower levels in larger tumours and tumours of more advanced stages. Based on the results of in vitro and in vivo experiments, up-regulation of uc.38 expression inhibited cell proliferation and induced cell apoptosis. Thus, uc.38 suppressed breast cancer. Additional experiments revealed that uc.38 negatively regulated the expression of the pre-B-cell leukaemia homeobox 1 (PBX1) protein and subsequently affected the expression of Bcl-2 family members, ultimately inducing breast cancer cell apoptosis. Describing the uc.38/PBX1 axis has improved our understanding of the molecular mechanisms involved in breast cancer apoptosis and has suggested that this axis is a potential therapeutic target for breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29312798", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 518, "text": "We found that overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447964", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 523, "text": "We found that overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447964", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 519, "text": "We found that overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447964", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1009, "text": "Our results reveal an important role of uc.63 in promoting breast cancer cells survival and offer the prospect to identify a signature associated with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447964", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1008, "text": "Our results reveal an important role of uc.63 in promoting breast cancer cells survival and offer the prospect to identify a signature associated with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447964", "endSection": "abstract" } ] }, { "body": "How many different miRNAs can be upregulated by LB-100?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28588271" ], "ideal_answer": [ "LB-100 has been reported to upregulate one miRNA, namely miR-181b-1." ], "exact_answer": [ "One" ], "type": "factoid", "id": "5e2a046caa19d74431000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28588271", "endSection": "title" }, { "offsetInBeginSection": 682, "offsetInEndSection": 989, "text": " LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3' untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28588271", "endSection": "abstract" } ] }, { "body": "Which T-UCRs have been implicated in gastric cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "http://www.ncbi.nlm.nih.gov/pubmed/26640143", "http://www.ncbi.nlm.nih.gov/pubmed/30323869" ], "ideal_answer": [ "Uc.160 is significantly down-regulated in gastric carcinomas and can inhibit the tumor growth both in vitro and in vivo, suggesting that uc.160 may be used as a diagnostic marker and therapeutic target of gastric malignancies. Uc.416+A is overexpressed in GC and is associated with cell growth through the regulation of IGFBP6 (insulin-like growth factor-binding protein 6) in gastric cancer (GC)." ], "exact_answer": [ [ "Uc.160+" ], [ "Uc.416+A" ] ], "type": "list", "id": "5e36ad01b5b409ea53000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Transcribed ultraconserved noncoding RNA uc.160 acts as a negative regulator in gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323869", "endSection": "title" }, { "offsetInBeginSection": 233, "offsetInEndSection": 1614, "text": "uc.160 was found to be a suppressive factor of cancer development, but its role has not been fully elucidated.METHODS: The uc.160 expression was examined in gastric cancer tissues and established cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological function of gastric cancer cells with uc.160 over-expression were investigated, and the interaction between uc.160 and microRNA miR-155 was examined by dual-luciferase reporter assay. PTEN levels were detected by Western blotting. Anti-tumor effects of uc.160 were further explored in tumor transplantation models.RESULTS: uc.160 expression was significantly down-regulated in gastric cancer tissues and gastric cell lines as compared to adjacent normal tissues and immortalized gastric epithelial cell line (GES-1), respectively. Over-expression of uc.160 in SGC-7901 and AGS gastric cancer cells significantly suppressed their proliferation in vitro and in vivo. Moreover, uc.160 positively regulated the tumor suppressor protein PTEN. Interestingly, uc.160 was inhibited by microRNA miR-155 that is also a negative regulator of gastric cancer.CONCLUSION: uc.160 is significantly down-regulated in gastric carcinomas and can inhibit the tumor growth both in vitro and in vivo, suggesting that uc.160 may be used as a diagnostic marker and therapeutic target of gastric malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Expression and function of Uc.160+, a transcribed ultraconserved region, in gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1592, "text": "BACKGROUND: Transcribed ultraconserved regions (T-UCRs) are a novel class of noncoding RNAs that are highly conserved among the orthologous regions in most vertebrates. It has been reported that T-UCRs have distinct signatures in human cancers. We previously discovered the downregulation of T-UCR expression in gastric cancer (GC), indicating that T-UCRs could play an important role in GC biology. Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.METHODS: We analyzed the expression pattern of Uc.160+ in nonneoplastic and tumor tissues of the stomach by using uantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), specifically focusing on the mechanism of transcriptional regulation and target genes that are regulated by T-UCRs. We also attempted to determine the effect of Uc.160+ expression on biological features of GC cell lines by Western blotting.RESULTS: On the basis of the qRT-PCR and ISH results, Uc.160+ expression in adenoma and GC tissues was clearly downregulated compared with that in nonneoplastic mucosa tissues of the stomach. Cancer-specific DNA methylation in the promoter region of Uc.160 was observed by bisulfite genomic DNA sequencing analysis. The effect of DNA methylation on Uc.160+ expression was further confirmed by reporter gene assay. We also revealed that Uc.160+ inhibited the phosphorylation of Akt by regulating phosphatase and tensin homolog (PTEN) expression.CONCLUSIONS: These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 1595, "text": "We investigated the transcriptional levels of representative 26 T-UCRs and determined the regions that were differently expressed in prostate cancer (PCa) and gastric cancer (GC). A quantitative reverse transcription-polymerase chain reaction analysis revealed the downregulation of Uc.158+A expression by a DNA methylation-associated mechanism, which was restored by 5-Aza-dC (5-aza-2'-deoxycytidine) treatment. Bisulfite genomic sequencing using cell lines and tissue samples demonstrated cancer-specific CpG hypermethylation in both GC and PCa. However, Uc.416+A was only overexpressed in GC and we identified an miR-153 binding site in the possible regulatory region of Uc.416+A using online databases. Along with a forced expression or knockdown of miR-153 in MKN-74 GC cells, the transcriptional levels of Uc.416+A were significantly disturbed. A luciferase reporter gene assay supported the direct regulation of Uc.416+A expression by miR-153. Furthermore, Uc.416+A was associated with cell growth through the regulation of IGFBP6 (insulin-like growth factor-binding protein 6) in GC. These findings suggest an oncogenic role of Uc.416+A in GC, which suggests that our approach would provide new insights into functional studies of T-UCRs in cancer biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26640143", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 491, "text": "Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1596, "text": "These findings suggest an oncogenic role of Uc.416+A in GC, which suggests that our approach would provide new insights into functional studies of T-UCRs in cancer biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26640143", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 491, "text": "Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 1064, "text": "RESULTS\nuc.160 expression was significantly down-regulated in gastric cancer tissues and gastric cell lines as compared to adjacent normal tissues and immortalized gastric epithelial cell line (GES-1), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323869", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1198, "text": "Over-expression of uc.160 in SGC-7901 and AGS gastric cancer cells significantly suppressed their proliferation in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323869", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1139, "text": "RESULTS: On the basis of the qRT-PCR and ISH results, Uc.160+ expression in adenoma and GC tissues was clearly downregulated compared with that in nonneoplastic mucosa tissues of the stomach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 1492, "offsetInEndSection": 1592, "text": "CONCLUSIONS: These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 823, "text": "METHODS: We analyzed the expression pattern of Uc.160+ in nonneoplastic and tumor tissues of the stomach by using uantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), specifically focusing on the mechanism of transcriptional regulation and target genes that are regulated by T-UCRs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28382457", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1595, "text": "These findings suggest an oncogenic role of Uc.416+A in GC, which suggests that our approach would provide new insights into functional studies of T-UCRs in cancer biology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26640143", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 515, "text": "METHODS: The uc.160 expression was examined in gastric cancer tissues and established cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323869", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 714, "text": "The biological function of gastric cancer cells with uc.160 over-expression were investigated, and the interaction between uc.160 and microRNA miR-155 was examined by dual-luciferase reporter assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323869", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1062, "text": "RESULTS: uc.160 expression was significantly down-regulated in gastric cancer tissues and gastric cell lines as compared to adjacent normal tissues and immortalized gastric epithelial cell line (GES-1), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30323869", "endSection": "abstract" } ] }, { "body": "Which disease can be treated with Anifrolumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29420200", "http://www.ncbi.nlm.nih.gov/pubmed/30588322", "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "http://www.ncbi.nlm.nih.gov/pubmed/29644080", "http://www.ncbi.nlm.nih.gov/pubmed/29644082", "http://www.ncbi.nlm.nih.gov/pubmed/29460699", "http://www.ncbi.nlm.nih.gov/pubmed/27663753" ], "ideal_answer": [ "Anifrolumab is a type I interferon (IFN) receptor antagonist that has been shown to be effective for moderate-to-severe systemic lupus erythematosus (SLE)." ], "exact_answer": [ "systemic lupus erythematosus" ], "type": "factoid", "id": "5e2902e48b3851296d000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "OBJECTIVES: In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29420200", "endSection": "abstract" }, { "offsetInBeginSection": 1637, "offsetInEndSection": 1811, "text": "CONCLUSIONS: LLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29420200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 310, "text": "A post-hoc analysis of pooled data from two Phase IIb trials (sifalimumab; NCT01283139, anifrolumab; NCT01438489) assessed the clinical significance of a Systemic Lupus Erythematosus (SLE) Responder Index (SRI(4)) response (Week 52) for 736 patients with moderate to severe SLE disease activity (study entry). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29460699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Objectives: To compare the pharmacokinetics (PK), safety and tolerability of subcutaneous (SC) and intravenous anifrolumab, an anti-type I interferon receptor monoclonal antibody in development for SLE, in healthy volunteers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644082", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Objective: We investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644082", "endSection": "abstract" }, { "offsetInBeginSection": 1590, "offsetInEndSection": 1844, "text": "Conclusions: Anifrolumab potently inhibits type I IFN-dependent signalling, including the type I IFN autoamplification loop, and is a promising therapeutic for patients with SLE and other diseases that exhibit chronic dysfunctional type I IFN signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1217, "text": "Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over the past 15 years. The results of Phase II trials were encouraging but rarely borne out by Phase III trials. Recent data, which are discussed in detail in this review, allowed belimumab\u00a0-\u00a0a monoclonal antibody against BLyS (B-lymphocyte stimulator)\u00a0-\u00a0to become the first biotherapy approved for use in SLE. Other molecules targeting B cells include the two anti-BLyS antibodies tabalumab and blisibimod; atacicept, which targets both BLyS and APRIL (a proliferation-inducing ligand); and the monoclonal antibody to CD22 epratuzumab. The rekindling of interest in the B-cell pathway has also driven new clinical research into rituximab, a monoclonal antibody targeting CD20 with evaluations of new strategies. A new and promising approach is the use of inhibitors of the type 1 interferon (IFN) pathway, of which the most promising is anifrolumab, a monoclonal antibody targeting the type 1 IFN receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27663753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "OBJECTIVE: To assess the efficacy and safety of anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate-to-severe systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" }, { "offsetInBeginSection": 2898, "offsetInEndSection": 3063, "text": "CONCLUSION: Anifrolumab substantially reduced disease activity compared with placebo across multiple clinical end points in the patients with moderate-to-severe SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Anifrolumab, an Anti-Interferon-\u03b1 Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "title" }, { "offsetInBeginSection": 2904, "offsetInEndSection": 3069, "text": "CONCLUSION\n\nAnifrolumab substantially reduced disease activity compared with placebo across multiple clinical end points in the patients with moderate-to-severe SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "OBJECTIVE\n\nTo assess the efficacy and safety of anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate-to-severe systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30588322", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "OBJECTIVE\nTo assess the efficacy and safety of anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate-to-severe systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1220, "text": "CONCLUSION: Anifrolumab substantially reduced disease activity compared with placebo across multiple clinical end points in the patients with moderate-to-severe SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" } ] }, { "body": "Which de novo mutation in FGFR cause achondroplasia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8078586" ], "ideal_answer": [ "Recurrent missense mutations in a CpG doublet of the transmembrane domain of the FGFR3 protein (glycine substituted with arginine at residue 380, G380R)." ], "exact_answer": [ "G380R" ], "type": "factoid", "id": "5e2e11a1fbd6abf43b000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1476, "text": "Achondroplasia, the most common cause of chondrodysplasia in man (1 in 15,000 live births), is a condition of unknown origin characterized by short-limbed dwarfism and macrocephaly. More than 90% of cases are sporadic and there is an increased paternal age at the time of conception of affected individuals, suggesting that de novo mutations are of paternal origin. Affected individuals are fertile and achondroplasia is transmitted as a fully penetrant autosomal dominant trait, accounting for rare familial forms of the disease (10%). In contrast, homozygous achondroplasia is usually lethal in the neonatal period and affects 25% of the offspring of matings between heterozygous achondroplasia parents. The gene responsible for achondroplasia has been mapped to chromosome 4p16.3 (refs 7, 8); the genetic interval encompassing the disease gene contains a member of the fibroblast-growth-factor receptor (FGFR3) family which is expressed in articular chondrocytes. Here we report the finding of recurrent missense mutations in a CpG doublet of the transmembrane domain of the FGFR3 protein (glycine substituted with arginine at residue 380, G380R) in 17 sporadic cases and 6 unrelated familial forms of achondroplasia. We show that the mutant genotype segregates with the disease in these families. Thus it appears that recurrent mutations of a single amino acid in the transmembrane domain of the FGFR3 protein account for all cases (23/23) of achondroplasia in our series.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8078586", "endSection": "abstract" } ] }, { "body": "List types of DNA lesions caused by UV light.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29450111", "http://www.ncbi.nlm.nih.gov/pubmed/29305302", "http://www.ncbi.nlm.nih.gov/pubmed/29405222" ], "ideal_answer": [ "cyclobutane pyrimidine dimers\npyrimidine pyrimidone photoproducts\n8-oxo-7,8-dihydroguanine" ], "exact_answer": [ [ "cyclobutane pyrimidine dimers", "CPD" ], [ "pyrimidine pyrimidone photoproducts", "(6-4)pp" ], [ "8-oxo-7,8-dihydroguanine", "8-oxoGua" ] ], "type": "list", "id": "5e46e8c13f5415952900000c", "snippets": [ { "offsetInBeginSection": 403, "offsetInEndSection": 608, "text": "The most energetic part of the solar spectrum at the Earth's surface (UVB, 280-320 nm) leads to the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (64PPs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29405222", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 930, "text": "Among those, 8-oxo-7,8-dihydroguanine (8-oxoGua) is the most frequent since it can be produced by several mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29405222", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 394, "text": "UV-induced deoxyribonucleic acid (DNA) lesions such as a cyclobutane pyrimidine dimer (CPD) and a (6-4) photoproduct ((6-4)pp),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29450111", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 420, "text": "DNA lesions such as those generated by UV light: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone photoproducts (6-4 PPs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29305302", "endSection": "abstract" } ] }, { "body": "Has istadefylline been considered as a treatment for Parkinson's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30232916" ], "ideal_answer": [ "Yes, istradefylline is a new drug developed for the treatment of Parkinson's disease." ], "exact_answer": "yes", "type": "yesno", "id": "5e2dac4efbd6abf43b00000f", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 312, "text": "Istradefylline (ISD) is a new drug developed for the treatment of Parkinson's disease (PD). It is an adenosine receptor A2A antagonists that will represent an important option for patients with advanced PD where it has been demonstrated efficacy in decreasing daily OFF time and is well tolerated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30232916", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 536, "text": "The objective of this review is to summarize evidences emerged from clinical studies that have demonstrated the efficacy of ISD in advanced parkinsonian patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30232916", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 847, "text": " ISD might represent an alternative option for patients with advanced PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30232916", "endSection": "abstract" } ] }, { "body": "In which cellular compartment do stress granules localize?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28894257", "http://www.ncbi.nlm.nih.gov/pubmed/23474818", "http://www.ncbi.nlm.nih.gov/pubmed/29035885", "http://www.ncbi.nlm.nih.gov/pubmed/23982513", "http://www.ncbi.nlm.nih.gov/pubmed/27057671", "http://www.ncbi.nlm.nih.gov/pubmed/22383896", "http://www.ncbi.nlm.nih.gov/pubmed/25148713", "http://www.ncbi.nlm.nih.gov/pubmed/29298433" ], "ideal_answer": [ "cytoplasm", "Stress granules (SGs) are cytoplasmic granules that are formed in cells when stress occurs.", "Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins", "Stress granules (SGs) are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and are characteristic to eukaryotic cells.", "Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins. Here, we show that Rbfox2 is a novel constituent of cytoplasmic stress granules, the translational silencing machinery assembled in response to cellular stress." ], "exact_answer": [ "cytoplasm" ], "type": "factoid", "id": "5c74285c7c78d694710000a3", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29298433", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 335, "text": "Here, we show that Rbfox2 is a novel constituent of cytoplasmic stress granules, the translational silencing machinery assembled in response to cellular stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28894257", "endSection": "abstract" }, { "offsetInBeginSection": 992, "offsetInEndSection": 1119, "text": "Stress prompted the formation of cytoplasmic granules in all subjects and in sporadic ALS FUS mislocalization to the cytoplasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29035885", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 534, "text": "In this study, we firstly have examined this punctate pattern of Sam68 re-localization in the cytoplasm, and observed the obvious recruitments of Sam68 to the EV71-induced stress granules (SGs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27057671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Stress granules (SGs) are cytoplasmic granules that are formed in cells when stress occurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25148713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Proteins that contain a functional Z-DNA-binding domain localize to cytoplasmic stress granules.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982513", "endSection": "title" }, { "offsetInBeginSection": 605, "offsetInEndSection": 757, "text": "We have previously shown that ADAR1(p150) localized to cytoplasmic stress granules in HeLa cells following either oxidative or interferon-induced stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23982513", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 878, "text": ". We also show that oxidative stress recruits mutant FUS to cytoplasmic stress granules where it is able to bind and sequester wild-type FUS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23474818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Sequestration of highly expressed mRNAs in cytoplasmic granules, P-bodies, and stress granules enhances cell viability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383896", "endSection": "title" } ] }, { "body": "Which software are used for the detection of selective sweeps?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26862394", "http://www.ncbi.nlm.nih.gov/pubmed/25838885", "http://www.ncbi.nlm.nih.gov/pubmed/23099783", "http://www.ncbi.nlm.nih.gov/pubmed/23777627", "http://www.ncbi.nlm.nih.gov/pubmed/28405579", "http://www.ncbi.nlm.nih.gov/pubmed/30271960" ], "ideal_answer": [ "Four open-source software releases (SweeD, SweepFinder, SweepFinder2, and OmegaPlus) are able to detect selective sweeps accurately. RAiSD (Raised Accuracy in Sweep Detection), an open-source software implements a parameter-free detection mechanism that relies on multiple signatures of a selective sweep via the enumeration of SNP vectors." ], "exact_answer": [ [ "SweeD" ], [ "SweepFinder" ], [ "SweepFinder2" ], [ "OmegaPlus" ], [ "RAiSD" ] ], "type": "list", "id": "5cd96eb2a49efeb44c000003", "snippets": [ { "offsetInBeginSection": 632, "offsetInEndSection": 854, "text": "Using gPLINK software to set quality control standards, a total of 34 304 SNPs were selected for statistical analysis. Fst values between two breeds were estimated with Genepop package and the average Fst value was 0.3209.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23099783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "SweeD: likelihood-based detection of selective sweeps in thousands of genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777627", "endSection": "title" }, { "offsetInBeginSection": 682, "offsetInEndSection": 794, "text": "It analyzes site frequency spectra and represents a substantial extension of the widely used SweepFinder program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777627", "endSection": "abstract" }, { "offsetInBeginSection": 796, "offsetInEndSection": 1013, "text": "The sequential version of SweeD is up to 22 times faster than SweepFinder and, more importantly, is able to analyze thousands of sequences. We also provide a parallel implementation of SweeD for multi-core processors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777627", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 681, "text": "We present SweeD (Sweep Detector), an open-source tool for the rapid detection of selective sweeps in whole genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777627", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 925, "text": "SmileFinder is a simple program that looks for diversity and divergence patterns consistent with selection sweeps by evaluating allele frequencies in windows, including neighboring loci from two or more populations of a diploid species against the genome-wide neutral expectation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25838885", "endSection": "abstract" }, { "offsetInBeginSection": 1968, "offsetInEndSection": 2163, "text": "Furthermore, we compare the accuracy of our open-source sweep-detection software OmegaPlus, which implements all four parallelization strategies presented here, with a variety of neutrality tests", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26862394", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1362, "text": "Additionally, we summarize the results of comparisons among four open-source software releases (SweeD, SweepFinder, SweepFinder2, and OmegaPlus) regarding sensitivity, specificity, and execution times. In equilibrium neutral models or mild bottlenecks, both SFS- and LD-based methods are able to detect selective sweeps accurately.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28405579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "RAiSD detects positive selection based on multiple signatures of a selective sweep and SNP vectors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30271960", "endSection": "title" }, { "offsetInBeginSection": 254, "offsetInEndSection": 506, "text": "We present RAiSD (Raised Accuracy in Sweep Detection), an open-source software that implements a novel, to our knowledge, and parameter-free detection mechanism that relies on multiple signatures of a selective sweep via the enumeration of SNP vectors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30271960", "endSection": "abstract" } ] }, { "body": "Which organs are primarily damaged in SLE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9458204", "http://www.ncbi.nlm.nih.gov/pubmed/26936891", "http://www.ncbi.nlm.nih.gov/pubmed/23229448" ], "ideal_answer": [ "The patients with SLE are mostly affected by renal, peripheral vascular, musculoskeletal and neurological damage. The skin and heart are also damaged very frequently.", "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently damaged organs. The heart is one of the most commonly damaged organs in SLE. Any part of the heart can be affected, including the pericardium, myocardium, coronary arteries, valves, and the conduction system" ], "exact_answer": [ [ "kidney" ], [ "skin" ], [ "vascular organs" ], [ "heart" ], [ "musculoskeletal organs" ], [ "brain" ] ], "type": "list", "id": "5c70273c7c78d69471000061", "snippets": [ { "offsetInBeginSection": 879, "offsetInEndSection": 1045, "text": "The patients with SLE and SS had the greatest renal, peripheral vascular, and musculoskeletal damage (24, 19, 38% of patients, respectively) followed by the SLE group", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9458204", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 385, "text": "Observations from lupus centres worldwide revealed that the prevalence of damage occurring in the cardiovascular system in patients with SLE has increased over the past four decades.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229448", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 642, "text": "lupus-related organ damage involving the neuropsychiatric and renal systems also remains a major factor that limits survival improvement in patients with this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229448", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1376, "text": "This Review discusses the pattern and trend of organ damage in patients with SLE worldwide, the potential serological and genetic mechanisms of organ damage, and the advances in research on potential tools for early detection of lupus-related organ damage, such as functional brain imaging techniques, measurement of endothelial function, identification of biomarkers from body fluids, and development of risk calculation models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229448", "endSection": "abstract" }, { "offsetInBeginSection": 1942, "offsetInEndSection": 2201, "text": " Patients with SLE treated with long-term belimumab plus SoC had a low incidence of organ damage accrual and no unexpected AEs. High-risk patients with pre-existing organ damage also had low accrual, suggesting a favorable effect on future damage development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26936891", "endSection": "abstract" } ] }, { "body": "What is Amyand hernia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29875977", "http://www.ncbi.nlm.nih.gov/pubmed/24303691", "http://www.ncbi.nlm.nih.gov/pubmed/29455120", "http://www.ncbi.nlm.nih.gov/pubmed/17990042", "http://www.ncbi.nlm.nih.gov/pubmed/23591313", "http://www.ncbi.nlm.nih.gov/pubmed/30049909", "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "http://www.ncbi.nlm.nih.gov/pubmed/19478627", "http://www.ncbi.nlm.nih.gov/pubmed/24765286", "http://www.ncbi.nlm.nih.gov/pubmed/30151100" ], "ideal_answer": [ "An Amyand hernia is a rare disease where the appendix is found within an inguinal hernia sac, which may or may not contain other abdominal contents or pathologic inflammatory changes." ], "type": "summary", "id": "5e2ad60e76af173751000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "INTRODUCTION: An Amyand's hernia is a heterogeneous clinical condition defined by the presence of the vermiform appendix within an inguinal hernia sac, which may or may not contain other abdominal contents or pathologic inflammatory changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29455120", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "INTRODUCTION: An Amyand hernia is a rare disease where the appendix is found within an inguinal hernia sac. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "endSection": "abstract" }, { "offsetInBeginSection": 1438, "offsetInEndSection": 1660, "text": "CONCLUSION: This case report reviews a rare entity known as an Amyand's hernia that presented as an incarcerated hernia that was diagnosed intraoperatively with an inflamed appendix, recognized as a type 2 Amyand's hernia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Claudius Amyand's hernia is defined as the incarceration of the vermiform appendix in the hernia sac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29875977", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 278, "text": "Amyand's hernia is an inguinal hernia; a protrusion of abdominal cavity content through the inguinal canal, with a vermiform appendix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30049909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "The presence of an incarcerated vermiform appendix within a femoral hernia defect, a De Garengeot hernia, is distinctly different than an inguinal hernia containing the appendix, an Amyand hernia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30151100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "INTRODUCTION\n\nAn Amyand hernia is a rare disease where the appendix is found within an inguinal hernia sac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "INTRODUCTION An Amyand hernia is a rare disease where the appendix is found within an inguinal hernia sac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The term Amyand hernia refers to presence of appendix within inguinal hernia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24765286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "BACKGROUND Amyand's hernia is an inguinal hernia containing vermiform appendix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17990042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Appendix-containing inguinal hernias are known as Amyand hernias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19478627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "An Amyand hernia is a rare disease where the appendix is found within an inguinal hernia sac . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 278, "text": "Amyand's hernia is an inguinal hernia; a protrusion of abdominal cavity content through the inguinal canal, with a vermiform appendix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30049909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The eponym 'Amyand hernia' coined in recognition of Claudius Amyand, the first surgeon to successfully perform appendectomy in a hernia sac containing appendix, refers to the vermiform appendix within inguinal hernia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23591313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The finding of the appendix inside an hernial sac is called \"Amyand hernia\": The global incidence is 0.28 to 1%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24303691", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 498, "text": " Introduction An Amyand hernia is a rare disease where the appendix is found within an inguinal hernia sac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "endSection": "abstract" }, { "offsetInBeginSection": 1463, "offsetInEndSection": 1621, "text": "Discussion The current generally accepted treatment algorithm for Amyand's hernia is essentially contingent on the appendix's condition within the hernia sac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753277", "endSection": "abstract" } ] }, { "body": "What is the Lupus Severity Index (LSI)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27026812" ], "ideal_answer": [ "It is a simple systemic lupus erythematosus (SLE) severity index that requires knowledge of only American College of Rheumatology (ACR) criteria and subcriteria.", "The Lupus Severity Index (LSI) is a simple, reliable, and valid measure of disease severity in patients with systemic lupus erythematosus.", "The Lupus Severity Index (LSI) is a simple, reliable, and valid measure of disease severity in patients with systemic lupus erythematosus. The index can be used to identify patients at risk for acute exacerbations of Lupus nephritis. Based on the score, patients were classified into five different groups, one with the most severe, the other with the worst prognosis, and the others with the best prognosis." ], "type": "summary", "id": "5c700c607c78d6947100005e", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 177, "text": "To develop a simple systemic lupus erythematosus (SLE) severity index that requires knowledge of only American College of Rheumatology (ACR) criteria and subcriteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27026812", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 323, "text": "This study used demographic, mortality and medical records data of 1915 patients with lupus from the Lupus Family Registry and Repository", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27026812", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1290, "text": "The index was also found to be strongly correlated with a previously existing severity score for lupus. In addition, demographic factors known to influence lupus severity (eg, age of onset, gender and ethnicity) all showed robust associations with our severity index that were consistent with observed clinical trends.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27026812", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 799, "text": "ACR criteria and subcriteria were used as predictor variables in this model, and the resulting regression coefficient estimates obtained from the training data were used as item weightings to construct the severity index", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27026812", "endSection": "abstract" } ] }, { "body": "Is amantadine ER the first approved treatment for akinesia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29564954" ], "ideal_answer": [ "No, extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia." ], "exact_answer": "no", "type": "yesno", "id": "5e2dad57fbd6abf43b000010", "snippets": [ { "offsetInBeginSection": 198, "offsetInEndSection": 307, "text": "Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29564954", "endSection": "abstract" } ] }, { "body": "Which disease is Dasatinib used to treat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29515069", "http://www.ncbi.nlm.nih.gov/pubmed/26951627", "http://www.ncbi.nlm.nih.gov/pubmed/27374826", "http://www.ncbi.nlm.nih.gov/pubmed/26300669", "http://www.ncbi.nlm.nih.gov/pubmed/22068151", "http://www.ncbi.nlm.nih.gov/pubmed/21828123", "http://www.ncbi.nlm.nih.gov/pubmed/24718698", "http://www.ncbi.nlm.nih.gov/pubmed/28795321", "http://www.ncbi.nlm.nih.gov/pubmed/29121645" ], "ideal_answer": [ "Patients with chronic myeloid leukemia", "Dasatinib is a second-generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib. A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood.", "Dasatinib is a pan receptor tyrosine kinase inhibitor (RTK) used in the treatment of chronic myelogenous leukemia (CML).", "chronic myeloid leukemia", "Dasatinib is a small molecule covalently binding and inhibiting BCR-ABL receptor. It is used for treatment of chronic myelogenous leukemia (CML) by targeting the integrins avb3 and avb5 over-expressed on B cells." ], "exact_answer": [ "Chronic myeloid leukemia", "CML" ], "type": "factoid", "id": "5c701f4f7c78d69471000060", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Patients with chronic myeloid leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21828123", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1106, "text": "Our results suggest that the characteristics of complete molecular response on dasatinib treatment may be similar to that achieved with imatinib, at least in patients with adverse disease features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21828123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Dasatinib as salvage therapy for steroid refractory and imatinib resistant or intolerant sclerotic chronic graft-versus-host disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068151", "endSection": "title" }, { "offsetInBeginSection": 359, "offsetInEndSection": 573, "text": "Dasatinib, a second-generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib, has also shown potent antifibrotic effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22068151", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1021, "text": "Furthermore, two recent studies showed dasatinib to be effective in inhibiting the in vitro growth of cells from leukemia patients with c-Cbl RING finger and linker domain mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24718698", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1329, "text": "Thus we conclude that dasatinib may not be an appropriate therapy for leukemia patients with c-Cbl mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24718698", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1041, "text": " With continuous dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26300669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26951627", "endSection": "title" }, { "offsetInBeginSection": 307, "offsetInEndSection": 515, "text": " We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26951627", "endSection": "abstract" }, { "offsetInBeginSection": 1850, "offsetInEndSection": 1988, "text": "This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26951627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28795321", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28795321", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 133, "text": "Mixed connective tissue disease with pulmonary hypertension developing in a chronic myeloid leukemia patient on dasatinib treatment]", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515069", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "A 37-year-old woman was diagnosed with chronic phase chronic myeloid leukemia. Nilotinib treatment was initiated; however, it had to be discontinued due to an allergic reaction one month later, and dasatinib treatment was provided. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29515069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29121645", "endSection": "title" } ] }, { "body": "Is g-H2AX a marker for double strand breaks?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29053406", "http://www.ncbi.nlm.nih.gov/pubmed/29540258", "http://www.ncbi.nlm.nih.gov/pubmed/29352998", "http://www.ncbi.nlm.nih.gov/pubmed/29462394" ], "ideal_answer": [ "Yes,\nThe specific phosphorylation of histone H2AX on serine residue 139, described as g-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs)." ], "exact_answer": "yes", "type": "yesno", "id": "5e480ccfd14c9f295d000005", "snippets": [ { "offsetInBeginSection": 151, "offsetInEndSection": 312, "text": "The specific phosphorylation of histone H2AX on serine residue 139, described as \u03b3-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29053406", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 734, "text": "expression of the DNA double-strand break marker gamma-H2AX (\u03b3H2AX) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29462394", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 742, "text": "pH2AX, a marker of the DNA double-strand break (DSB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540258", "endSection": "abstract" } ] }, { "body": "Which algorithm has been developed for finding conserved non-coding elements (CNEs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30423090" ], "ideal_answer": [ "CNEFinder is a tool for identifying CNEs between two given DNA sequences with user-defined criteria.", "CNEFinder is an algorithm which has been developed for finding conserved non-coding elements (CNEs)." ], "exact_answer": [ "CNEFinder" ], "type": "factoid", "id": "5e2894109499698331000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "CNEFinder: finding conserved non-coding elements in genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "title" }, { "offsetInBeginSection": 308, "offsetInEndSection": 657, "text": "Towards this direction, identifying sets of CNEs in a wide range of organisms is an important first step. Currently, there are no tools published in the literature for systematically identifying CNEs in genomes.Results: We fill this gap by presenting CNEFinder; a tool for identifying CNEs between two given DNA sequences with user-defined criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 659, "text": "Results\nWe fill this gap by presenting CNEFinder; a tool for identifying CNEs between two given DNA sequences with user-defined criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30423090", "endSection": "abstract" } ] }, { "body": "What type of antagonist is istradefylline?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28870576" ], "ideal_answer": [ "Istradefylline is a selective adenosine A2A receptor antagonist." ], "exact_answer": [ "Selective adenosine A2A receptor antagonist" ], "type": "factoid", "id": "5e2daaa2fbd6abf43b00000e", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 183, "text": " Istradefylline, a selective adenosine A2A receptor antagonist, has been reported to improve daily \"off time\" and motor symptoms in patients with Parkinson's disease (PD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28870576", "endSection": "abstract" } ] }, { "body": "What are the advantages of liquid biopsy in NSCLC?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29885479", "http://www.ncbi.nlm.nih.gov/pubmed/25137181", "http://www.ncbi.nlm.nih.gov/pubmed/27285610", "http://www.ncbi.nlm.nih.gov/pubmed/30174936" ], "ideal_answer": [ "Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure.", ". These plasma-isolated exosomes can be used as a non-invasive and repeatable way for the detection and follow-up of these biomarkers.. We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact.. In summary, the panel concluded that liquid biopsy approaches have significant potential to improve patient care, and immediate implementation in the clinic is justified in a number of therapeutic settings relevant to NSCLC.. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution.. In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status.", "Mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status. Plasma-isolated exosomes can be used as a non-invasive and repeatable way for the detection and follow-up of these biomarkers. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. Complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution." ], "exact_answer": [ [ "real-time information" ], [ "non-invasive" ], [ "reflects spatiotemporal heterogeneity" ] ], "type": "list", "id": "5c7a4ed5d774d04240000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137181", "endSection": "title" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 1903, "text": "We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137181", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 306, "text": "In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Exosomal miRNA Analysis in Non-small Cell Lung Cancer (NSCLC) Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27285610", "endSection": "title" }, { "offsetInBeginSection": 309, "offsetInEndSection": 441, "text": "These plasma-isolated exosomes can be used as a non-invasive and repeatable way for the detection and follow-up of these biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27285610", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1316, "text": "Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30174936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The isolation and analysis of circulating cell-free tumor DNA in plasma is a powerful tool with considerable potential to improve clinical outcomes across multiple cancer types, including NSCLC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29885479", "endSection": "abstract" }, { "offsetInBeginSection": 1526, "offsetInEndSection": 1750, "text": "In summary, the panel concluded that liquid biopsy approaches have significant potential to improve patient care, and immediate implementation in the clinic is justified in a number of therapeutic settings relevant to NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29885479", "endSection": "abstract" } ] }, { "body": "What is the 4D-CHAINS algorithm?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29374165" ], "ideal_answer": [ "The 4D-CHAINS/autoNOE-Rosetta is a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta." ], "type": "summary", "id": "5e2d80cafbd6abf43b00000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1076, "text": "Automated methods for NMR structure determination of proteins are continuously becoming more robust. However, current methods addressing larger, more complex targets rely on analyzing 6-10 complementary spectra, suggesting the need for alternative approaches. Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta. Our results on four targets ranging in size from 15.5 to 27.3\u2009kDa illustrate that the structures of proteins can be determined accurately and in an unsupervised manner in a matter of days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 753, "text": "The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 887, "text": "The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 400, "text": "Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 761, "text": "The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single , fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 406, "text": "Here , we describe 4D-CHAINS/autoNOE-Rosetta , a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 895, "text": "The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 754, "text": "The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 888, "text": "The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 401, "text": "Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374165", "endSection": "abstract" } ] }, { "body": "Which disorders are caused by de novo mutations in ZSWIM6?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26706854", "http://www.ncbi.nlm.nih.gov/pubmed/29198722", "http://www.ncbi.nlm.nih.gov/pubmed/25105228" ], "ideal_answer": [ "Mutations in the ZSWIM6 gene, which encodes the cellular iron exporter ZEB6, are the cause of de novo autosomal recessive acromelic frontonasal dysostosis and Leber's hereditary optic neuropathy and/or dystonia.", "A recurrent de novo nonsense variant in ZSWIM6 results in severe intellectual disability without frontonasal or limb malformations. Also, a recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 has previously been reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect.", "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal ZSWIM6 protein, are the cause of autosomal recessive acromelic frontonasal dysostosis and Leber's hereditary optic neuropathy and/or dystonia." ], "exact_answer": [ [ "Severe intellectual disability without frontonasal or limb malformations" ], [ "Acromelic frontonasal dysostosis", "AFND" ] ], "type": "list", "id": "5e2b0d167d50947c2f000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe Intellectual Disability without Frontonasal or Limb Malformations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198722", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "A recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198722", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 1199, "text": "We show that the c.2737C>T variant does not trigger nonsense-mediated decay of the ZSWIM6 mRNA in affected individual-derived cells. This finding supports the existence of a truncated ZSWIM6 protein lacking the Sin3-like domain, which could have a dominant-negative effect. This study builds support for a key role for ZSWIM6 in neuronal development and function, in addition to its putative roles in limb and craniofacial development, and provides a striking example of different variants in the same gene leading to distinct phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Exome sequencing identifies a recurrent de novo ZSWIM6 mutation associated with acromelic frontonasal dysostosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105228", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1334, "text": "Acromelic frontonasal dysostosis (AFND) is a rare disorder characterized by distinct craniofacial, brain, and limb malformations, including frontonasal dysplasia, interhemispheric lipoma, agenesis of the corpus callosum, tibial hemimelia, preaxial polydactyly of the feet, and intellectual disability. Exome sequencing of one trio and two unrelated probands revealed the same heterozygous variant (c.3487C>T [p. Arg1163Trp]) in a highly conserved protein domain of ZSWIM6; this variant has not been seen in the 1000 Genomes data, dbSNP, or the Exome Sequencing Project. Sanger validation of the three trios confirmed that the variant was de novo and was also present in a fourth isolated proband. In situ hybridization of early zebrafish embryos at 24 hr postfertilization (hpf) demonstrated telencephalic expression of zswim6 and onset of midbrain, hindbrain, and retinal expression at 48 hpf. Immunohistochemistry of later-stage mouse embryos demonstrated tissue-specific expression in the derivatives of all three germ layers. qRT-PCR expression analysis of osteoblast and fibroblast cell lines available from two probands was suggestive of Hedgehog pathway activation, indicating that the ZSWIM6 mutation associated with AFND may lead to the craniofacial, brain and limb malformations through the disruption of Hedgehog signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "A recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198722", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 660, "text": "We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C>T [p.Arg913Ter]) in the penultimate exon of ZSWIM6 who have severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Exome sequencing identifies a recurrent de novo ZSWIM6 mutation associated with acromelic frontonasal dysostosis .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105228", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "A recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198722", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 332, "text": "A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26706854", "endSection": "abstract" } ] }, { "body": "Describe ChromoTrace", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29522506" ], "ideal_answer": [ "Recent advances of super-resolution microscopy in principle enable the mapping of specific molecular features with nanometer precision inside cells. Combined with highly specific, sensitive and multiplexed fluorescence labeling of DNA sequences this opens up the possibility of mapping the 3D path of the genome sequence in situ. ChromoTrace is a computational methodology to reconstruct the sequence configuration of all human chromosomes in the nucleus from a super-resolution image of a set of fluorescent in situ probes hybridized to the genome in a cell. ChromoTrace uses suffix trees to assign a known linear ordering of in situ probes on the genome to an unknown set of 3D in-situ probe positions in the nucleus from super-resolved images using the known genomic probe spacing as a set of physical distance constraints between probes. The algorithm can assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences.", "ChromoTrace is a computational tool to reconstruct the sequence configuration of all human chromosomes in the nucleus from a super-resolution image of a set of fluorescent in situ probes hybridized to the genome in a cell. It can be used to assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences. By simulating appropriate spatial resolution, label multiplexing and noise scenarios it is possible to assess the algorithms performance." ], "type": "summary", "id": "5e369c30b5b409ea53000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "ChromoTrace: Computational reconstruction of 3D chromosome configurations for super-resolution microscopy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1941, "text": "The 3D structure of chromatin plays a key role in genome function, including gene expression, DNA replication, chromosome segregation, and DNA repair. Furthermore the location of genomic loci within the nucleus, especially relative to each other and nuclear structures such as the nuclear envelope and nuclear bodies strongly correlates with aspects of function such as gene expression. Therefore, determining the 3D position of the 6 billion DNA base pairs in each of the 23 chromosomes inside the nucleus of a human cell is a central challenge of biology. Recent advances of super-resolution microscopy in principle enable the mapping of specific molecular features with nanometer precision inside cells. Combined with highly specific, sensitive and multiplexed fluorescence labeling of DNA sequences this opens up the possibility of mapping the 3D path of the genome sequence in situ. Here we develop computational methodologies to reconstruct the sequence configuration of all human chromosomes in the nucleus from a super-resolution image of a set of fluorescent in situ probes hybridized to the genome in a cell. To test our approach, we develop a method for the simulation of DNA in an idealized human nucleus. Our reconstruction method, ChromoTrace, uses suffix trees to assign a known linear ordering of in situ probes on the genome to an unknown set of 3D in-situ probe positions in the nucleus from super-resolved images using the known genomic probe spacing as a set of physical distance constraints between probes. We find that ChromoTrace can assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences. By simulating appropriate spatial resolution, label multiplexing and noise scenarios we assess our algorithms performance. Our study shows that it is feasible to achieve genome-wide reconstruction of the 3D DNA path based on super-resolution microscopy images.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1527, "text": "Our reconstruction method, ChromoTrace, uses suffix trees to assign a known linear ordering of in situ probes on the genome to an unknown set of 3D in-situ probe positions in the nucleus from super-resolved images using the known genomic probe spacing as a set of physical distance constraints between probes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1680, "text": "We find that ChromoTrace can assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1681, "text": "We find that ChromoTrace can assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1528, "text": "Our reconstruction method, ChromoTrace, uses suffix trees to assign a known linear ordering of in situ probes on the genome to an unknown set of 3D in-situ probe positions in the nucleus from super-resolved images using the known genomic probe spacing as a set of physical distance constraints between probes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "abstract" }, { "offsetInBeginSection": 2675, "offsetInEndSection": 2837, "text": "Our method, ChromoTrace, uses a computer science data structure, suffix trees, that allow one to simultaneous search the entire genome for specific sub-sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "abstract" }, { "offsetInBeginSection": 3032, "offsetInEndSection": 3112, "text": "ChromoTrace can robustly and accurately reconstruct 3D paths in our simulations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29522506", "endSection": "abstract" } ] }, { "body": "What is the aim of iodine prophylaxis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27655110", "http://www.ncbi.nlm.nih.gov/pubmed/10566200", "http://www.ncbi.nlm.nih.gov/pubmed/17205086" ], "ideal_answer": [ "Due to high volatility and environmental mobility, radioactive isotopes of iodine pose a serious risk in the acute phases of a nuclear accident. The critical organ for iodine is the thyroid. A number of studies dealing with thyroid protection from exposure to radioiodine have shown that radioiodine uptake by the thyroid can be effectively blocked by administration of stable iodine, usually in the form of potassium iodide (KI) pills." ], "type": "summary", "id": "5e48339fd14c9f295d00000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "A potential radiation protection method to reduce the risk of adverse health outcomes in the case of accidental radioactive iodine release is the administration of potassium iodide (KI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Radioactive iodine isotopes may be released to air to a varying degree during accidents with nuclear reactors. Iodine tablets, taken before or shortly after such release, protect against intake of radioactive iodine isotopes, but not against other radionuclides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17205086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 436, "text": "Due to high volatility and environmental mobility, radioactive isotopes of iodine pose a serious risk in the acute phases of a nuclear accident. The critical organ for iodine is the thyroid. A number of studies dealing with thyroid protection from exposure to radioiodine have shown that radioiodine uptake by the thyroid can be effectively blocked by administration of stable iodine, usually in the form of potassium iodide (KI) pills.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10566200", "endSection": "abstract" } ] }, { "body": "Through which molecular pathway does LB-100 reduce hepatic steatosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31832001" ], "ideal_answer": [ "PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway." ], "exact_answer": [ "AMPK/Sirt1 pathway" ], "type": "factoid", "id": "5e2a080caa19d7443100000a", "snippets": [ { "offsetInBeginSection": 2029, "offsetInEndSection": 2186, "text": " PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31832001", "endSection": "abstract" } ] }, { "body": "Which drugs are included in PolyIran?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26265520", "http://www.ncbi.nlm.nih.gov/pubmed/25230980", "http://www.ncbi.nlm.nih.gov/pubmed/28882196" ], "ideal_answer": [ "PolyIran polypill is composed of acetylsalicylic acid, hydrochlorothiazide, enalapril, and atorvastatin, whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials." ], "exact_answer": [ [ "acetylsalicylic acid" ], [ "hydrochlorothiazide" ], [ "enalapril" ], [ "atorvastatin" ] ], "type": "list", "id": "5e2f9ceefbd6abf43b000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 417, "text": "A new chromatographic-densitometric method has been developed for the qualitative and quantitative determination of the active ingredients in a simulated mixture corresponding to the PolyIran polypill, composed of acetylsalicylic acid, hydrochlorothiazide (HCT), enalapril (ENA), and atorvastatin (ATR), whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28882196", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 715, "text": "DESIGN AND METHODS: The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25230980", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 847, "text": "We designed a study to investigate the effects of a simpler strategy: a fixed-dose combination pill consisting of aspirin, valsartan, atorvastatin and hydrochlorthiazide (PolyPill) in an unselected group of persons aged over 50 years.DESIGN: The PolyIran-Liver study was performed in Gonbad city as an open label pragmatic randomized controlled trial nested within the Golestan Cohort Study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26265520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "A new chromatographic-densitometric method has been developed for the qualitative and quantitative determination of the active ingredients in a simulated mixture corresponding to the PolyIran polypill, composed of acetylsalicylic acid, hydrochlorothiazide (HCT), enalapril (ENA), and atorvastatin (ATR), whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28882196", "endSection": "abstract" } ] }, { "body": "Are tumour specific antigens originating from known protein coding genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1423320", "http://www.ncbi.nlm.nih.gov/pubmed/18031135", "http://www.ncbi.nlm.nih.gov/pubmed/12766764", "http://www.ncbi.nlm.nih.gov/pubmed/21388431", "http://www.ncbi.nlm.nih.gov/pubmed/11599633", "http://www.ncbi.nlm.nih.gov/pubmed/7517178", "http://www.ncbi.nlm.nih.gov/pubmed/23561850" ], "ideal_answer": [ "Heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP. Tumour antigens are mostly of weak immunogenicity, because the vast majority are tumour-associated differentiation antigens already 'seen' by the patient's immune system.", "heat-shock proteins (hsps)", "The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP.", "It is well established that MHC class I molecules present peptides from endogenous proteins, such as virus or tumour antigens, to CD8+ T lymphocytes. So far, human tumour specific antigens that can be presented by HLA molecules have not been identified on the molecular level. The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP.", "D" ], "exact_answer": "yes", "type": "yesno", "id": "5c7f806d617e120c34000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "It is well established that MHC class I molecules present peptides from endogenous proteins, such as virus or tumour antigens, to CD8+ T lymphocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1423320", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 859, "text": "So far, human tumour specific antigens that can be presented by HLA molecules have not been identified on the molecular level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1423320", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 331, "text": "These CTLs recognize short peptides derived from tumour-associated antigens in conjunction with class I molecules expressed on tumour cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7517178", "endSection": "abstract" }, { "offsetInBeginSection": 1508, "offsetInEndSection": 1724, "text": " The focus on cellular immune responses, combined with rapid biotechnological advances, resulted in the identification of tumour specific antigens, such as MART-1 and gp100, that could be recognised by autologous TIL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18031135", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 971, "text": " Tumour antigens are mostly of weak immunogenicity, because the vast majority are tumour-associated differentiation antigens already 'seen' by the patient's immune system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11599633", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1360, "text": "Tumour-specific antigens, which could be a more potent target for immunotherapy, mostly arise by point mutations and have the disadvantage of being not only tumour-specific, but also individual-specific.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11599633", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 574, "text": "The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12766764", "endSection": "abstract" }, { "offsetInBeginSection": 1327, "offsetInEndSection": 1538, "text": "Therefore, we propose that CD4(+) T cells that recognize secreted TSA may be superior for immunotherapy by T cell transfer, because the local extracellular antigen concentration will be higher for secreted TSA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21388431", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 457, "text": " Here, we wondered whether these frame-shifted peptide (FSP) sequences represent tumour-specific antigens also for MSI(+) leukaemia and lymphomas (L/L).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23561850", "endSection": "abstract" }, { "offsetInBeginSection": 1595, "offsetInEndSection": 1692, "text": "Data presented here expand the importance of FSPs as shared and general tumour-specific antigens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23561850", "endSection": "abstract" } ] }, { "body": "Mutations in which gene form the genetic basis of the DOORS syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25169878", "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "http://www.ncbi.nlm.nih.gov/pubmed/27259978", "http://www.ncbi.nlm.nih.gov/pubmed/25557349", "http://www.ncbi.nlm.nih.gov/pubmed/30335140" ], "ideal_answer": [ "Mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes. Thus, individuals with DOORS syndrome without deafness and seizures but with the other features should still be screened for TBC1D24 mutations. More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24." ], "exact_answer": [ "TBC1D24" ], "type": "factoid", "id": "5e2e1792fbd6abf43b000024", "snippets": [ { "offsetInBeginSection": 1383, "offsetInEndSection": 2638, "text": "We identified TBC1D24 mutations in 11 individuals from nine families (by exome sequencing in seven families, and Sanger sequencing in two families). 18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families. The seizure types in individuals with TBC1D24 mutations included generalised tonic-clonic, complex partial, focal clonic, and infantile spasms. Of the 18 individuals with DOORS syndrome from 17 families without TBC1D24 mutations, eight did not have seizures and three did not have deafness. In expression studies, some mutations abrogated TBC1D24 mRNA stability. We also detected Tbc1d24 expression in mouse phalangeal chondrocytes and calvaria, which suggests a role of TBC1D24 in skeletogenesis.INTERPRETATION: Our findings suggest that mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes. Thus, individuals with DOORS syndrome without deafness and seizures but with the other features should still be screened for TBC1D24 mutations. More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 2175, "offsetInEndSection": 2319, "text": "INTERPRETATION\n\nOur findings suggest that mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 1536, "offsetInEndSection": 1675, "text": "18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 2320, "offsetInEndSection": 2463, "text": "Thus, individuals with DOORS syndrome without deafness and seizures but with the other features should still be screened for TBC1D24 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 1074, "text": "Mutations in another BAF complex gene (SMARCA2) and (TBC1D24) were found to cause clinically similar conditions with ID, Nicolaides-Baraitser syndrome and DOORS syndrome, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25169878", "endSection": "abstract" }, { "offsetInBeginSection": 2169, "offsetInEndSection": 2312, "text": "INTERPRETATION Our findings suggest that mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1670, "text": "18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "BACKGROUND Recent studies have shown that recessive mutations in the TBC1D24 gene cause a variety of epilepsy syndromes, DOORS syndrome and nonsyndromic deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25557349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "Mutations in the Tre2/Bub2/Cdc16 ( TBC)1 domain family member 24 ( TBC1D24 ) gene are associated with a range of inherited neurological disorders , from drug-refractory lethal epileptic encephalopathy and DOORS syndrome ( deafness , onychodystrophy , osteodystrophy , mental retardation , seizures ) to non-syndromic hearing loss . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335140", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1107, "text": "Mutations in another BAF complex gene ( SMARCA2 ) and ( TBC1D24 ) were found to cause clinically similar conditions with ID , Nicolaides-Baraitser syndrome and DOORS syndrome , respectively . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25169878", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 1052, "text": "At present , it is unknown how different mutations of TBC1D24 cause non-syndromic deafness ( DFNB86 , OMIM 614617) , epilepsy ( OMIM 605021) , epilepsy with deafness , or DOORS syndrome ( OMIM 220500 ) that is characterized by deafness , onychodystrophy ( alteration of toenail or fingernail morphology) , osteodystrophy ( defective development of bone) , mental retardation , and seizures . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27259978", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1675, "text": "18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 1819, "offsetInEndSection": 1966, "text": "Of the 18 individuals with DOORS syndrome from 17 families without TBC1D24 mutations, eight did not have seizures and three did not have deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1671, "text": "18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 1816, "offsetInEndSection": 1962, "text": "Of the 18 individuals with DOORS syndrome from 17 families without TBC1D24 mutations, eight did not have seizures and three did not have deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 2169, "offsetInEndSection": 2313, "text": "INTERPRETATION: Our findings suggest that mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 2314, "offsetInEndSection": 2457, "text": "Thus, individuals with DOORS syndrome without deafness and seizures but with the other features should still be screened for TBC1D24 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 2458, "offsetInEndSection": 2638, "text": "More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 1016, "text": "At present, it is unknown how different mutations of TBC1D24 cause non-syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27259978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Recent studies have shown that recessive mutations in the TBC1D24 gene cause a variety of epilepsy syndromes, DOORS syndrome and nonsyndromic deafness.METHODS/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25557349", "endSection": "abstract" }, { "offsetInBeginSection": 1539, "offsetInEndSection": 1678, "text": "18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 1823, "offsetInEndSection": 1969, "text": "Of the 18 individuals with DOORS syndrome from 17 families without TBC1D24 mutations, eight did not have seizures and three did not have deafness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" }, { "offsetInBeginSection": 2177, "offsetInEndSection": 2320, "text": "Interpretation Our findings suggest that mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24291220", "endSection": "abstract" } ] }, { "body": "What is the aim of the \"Radiogenomics Consortium\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27515689", "http://www.ncbi.nlm.nih.gov/pubmed/29888979", "http://www.ncbi.nlm.nih.gov/pubmed/27979370", "http://www.ncbi.nlm.nih.gov/pubmed/28865512" ], "ideal_answer": [ "A major aim of research in radiogenomics is the development of a predictive instrument to enable identification of people who are at greatest risk for adverse effects resulting from cancer treatment using radiation. An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics." ], "exact_answer": [ "Pre-identification of people who are at greatest risk for adverse effects resulting from cancer treatment using radiation." ], "type": "factoid", "id": "5e48efd9f8b2df0d49000004", "snippets": [ { "offsetInBeginSection": 1167, "offsetInEndSection": 1378, "text": "An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29888979", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1192, "text": "A major aim of research in radiogenomics is the development of a predictive instrument to enable identification of people who are at greatest risk for adverse effects resulting from cancer treatment using radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28865512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Optimal design and patient selection for interventional trials using radiogenomic biomarkers", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27979370", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27515689", "endSection": "abstract" } ] }, { "body": "Who should wear dosimeters?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11948264", "http://www.ncbi.nlm.nih.gov/pubmed/28990968", "http://www.ncbi.nlm.nih.gov/pubmed/30451566" ], "ideal_answer": [ "Nuclear medicine technologists rely on a single dosimeter to measure their work-related dose. Dosimetry for the study of medical radiation workers." ], "type": "summary", "id": "5e49032df8b2df0d49000008", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 105, "text": "Nuclear medicine technologists rely on a single dosimeter to measure their work-related dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11948264", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 202, "text": " The reconstruction of lifetime radiation doses for medical workers presents special challenges not commonly encountered for the other worker cohorts comprising the Million Worker Study (MWS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30451566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Dosimetry for the study of medical radiation workers with a focus on the mean absorbed dose to the lung, brain and other organs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30451566", "endSection": "title" }, { "offsetInBeginSection": 137, "offsetInEndSection": 311, "text": "In the radiation safety field there is an increasing recognition of the value of dosimetry-related data that can be used to enhance safety programs and regulatory compliance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28990968", "endSection": "abstract" } ] }, { "body": "What kind of molecule is AZD8601?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30504800" ], "ideal_answer": [ "AZD8601 is a modified mRNA." ], "exact_answer": [ "mRNA" ], "type": "factoid", "id": "5e2a1096aa19d7443100000e", "snippets": [ { "offsetInBeginSection": 488, "offsetInEndSection": 662, "text": "Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30504800", "endSection": "abstract" } ] }, { "body": "Which disease category is LB-100 mostly assessed for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26799670", "http://www.ncbi.nlm.nih.gov/pubmed/28039265", "http://www.ncbi.nlm.nih.gov/pubmed/29294092" ], "ideal_answer": [ "LB-100 is designed to sensitize cancer cells to DNA damage from irradiation and chemotherapy. It is assessed for its therapeutic potential against cancer." ], "exact_answer": [ "Cancer" ], "type": "factoid", "id": "5e29f6e0aa19d74431000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Protein phosphatase 2A inhibition enhances radiation sensitivity and reduces tumor growth in chordoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29294092", "endSection": "title" }, { "offsetInBeginSection": 290, "offsetInEndSection": 563, "text": "LB100 is a small-molecule inhibitor of PP2A designed to sensitize cancer cells to DNA damage from irradiation and chemotherapy. A recently completed phase I trial of LB100 in solid tumors demonstrated its safety. Here, we show the therapeutic potential of LB100 in chordoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29294092", "endSection": "abstract" }, { "offsetInBeginSection": 1446, "offsetInEndSection": 1572, "text": "Animals implanted with chordoma cells and treated with the combination of LB100 and radiation demonstrated tumor growth delay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29294092", "endSection": "abstract" }, { "offsetInBeginSection": 1585, "offsetInEndSection": 1810, "text": "Combining LB100 and radiation enhanced DNA damage-induced cell death and delayed tumor growth in an animal model of chordoma. PP2A inhibition by LB100 treatment may improve the effectiveness of radiation therapy for chordoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29294092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "PP2A inhibition with LB100 enhances cisplatin cytotoxicity and overcomes cisplatin resistance in medulloblastoma cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26799670", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 594, "text": "The protein phosphatase 2A (PP2A) inhibitor, LB100, has been shown in pre-clinical studies to be an effective chemo- and radio-sensitizer for treatment of various cancers. We investigated effects associated with LB100 treatment alone and in combination with cisplatin for medulloblastoma (MB) in vitro and in vivo in an intracranial xenograft model. We demonstrated that LB100 had a potent effect on MB cells. By itself, LB100 inhibited proliferation and induced significant apoptosis in a range of pediatric MB cell lines. It also attenuated MB cell migration, a pre-requirement for invasion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26799670", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1192, "text": "Finally, LB100 exhibited potent in vivo anti-neoplastic activity in combination with cisplatin in an intracranial xenograft model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26799670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28039265", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 226, "text": "To determine the MTD and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28039265", "endSection": "abstract" }, { "offsetInBeginSection": 1436, "offsetInEndSection": 1627, "text": "The safety, tolerability, preliminary evidence of antitumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28039265", "endSection": "abstract" } ] }, { "body": "Which disease can be classified using the Koos Classification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30058759", "http://www.ncbi.nlm.nih.gov/pubmed/30339649", "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "http://www.ncbi.nlm.nih.gov/pubmed/29614352" ], "ideal_answer": [ "The Koos classification is used from vestibular schwannomas. It is designed to stratify tumors based on extrameatal extension and compression of the brainstem." ], "exact_answer": [ "vestibular schwannomas" ], "type": "factoid", "id": "5e2b2c85fbd6abf43b000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "INTRODUCTION: Grade IV vestibular schwannoma (Koos classification) is generally considered to be an indication for microsurgical resection or combined radiosurgery-microsurgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29614352", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 383, "text": "METHODS: The study included a total of 142 patients with VS stage 1 or 2 according to the Koos classification and treated between January 2004 and December 2015.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30058759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Koos Classification of Vestibular Schwannomas: A Reliability Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "BACKGROUND: The Koos classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1307, "text": "CONCLUSION: We have demonstrated that the Koos classification system for vestibular schwannoma is a reliable method for tumor classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 528, "text": "PATIENTS: Eighteen patients who underwent a middle fossa craniotomy for vestibular schwannoma (stage I or II of Koos classification) with attempted hearing preservation from January 2008 to February 2016 were retrospectively reviewed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30339649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND\n\nThe Koos classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1315, "text": "CONCLUSION\n\nWe have demonstrated that the Koos classification system for vestibular schwannoma is a reliable method for tumor classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1306, "text": "CONCLUSION We have demonstrated that the Koos classification system for vestibular schwannoma is a reliable method for tumor classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Grade IV vestibular schwannoma ( Koos classification ) is generally considered to be an indication for microsurgical resection or combined radiosurgery-microsurgery . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29614352", "endSection": "abstract" }, { "offsetInBeginSection": 1173, "offsetInEndSection": 1314, "text": "CONCLUSION\nWe have demonstrated that the Koos classification system for vestibular schwannoma is a reliable method for tumor classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND\nThe Koos classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1311, "text": "CONCLUSION: We have demonstrated that the Koos classification system for vestibular schwannoma is a reliable method for tumor classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169695", "endSection": "abstract" } ] }, { "body": "What is circulating free DNA ( cfDNA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26697469", "http://www.ncbi.nlm.nih.gov/pubmed/27422709", "http://www.ncbi.nlm.nih.gov/pubmed/25896555", "http://www.ncbi.nlm.nih.gov/pubmed/23674341", "http://www.ncbi.nlm.nih.gov/pubmed/29175734", "http://www.ncbi.nlm.nih.gov/pubmed/29314147" ], "ideal_answer": [ "Known to be present in the blood of cancer patients for decades, cell-free DNA (cfDNA) is beginning to inform on tumor genetics, tumor burden, and mechanisms of progression and drug resistance.", "Cell-free DNA (cfDNA) and cell-free RNA (cfRNA), RNA associated to platelets and circulating tumor cells (CTCs) are some of the materials that can be derived from the blood of cancer patients." ], "type": "summary", "id": "5cc0817da49efeb44c000002", "snippets": [ { "offsetInBeginSection": 655, "offsetInEndSection": 847, "text": "Cell-free DNA (cfDNA) and cell-free RNA (cfRNA), RNA associated to platelets and circulating tumor cells (CTCs) are some of the materials that can be derived from the blood of cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26697469", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 602, "text": "Known to be present in the blood of cancer patients for decades, cell-free DNA (cfDNA) is beginning to inform on tumor genetics, tumor burden, and mechanisms of progression and drug resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27422709", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 192, "text": "This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) to replace conventional screening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23674341", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 467, "text": "cfDNA was isolated from a serum specimen before chemotherapy. Its value was correlated to recurrence-free and overall survival using Kaplan-Meier curves. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25896555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Cell-free fetal DNA analysis for non-invasive prenatal screening of fetal chromosomal aneuploidy has been widely adopted for clinical use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29314147", "endSection": "abstract" } ] }, { "body": "What are the in vivo effects of AZD8601?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30504800" ], "ideal_answer": [ "AZD8601 administration in vivo results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing." ], "type": "summary", "id": "5e2a120c76af173751000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30504800", "endSection": "title" }, { "offsetInBeginSection": 662, "offsetInEndSection": 1410, "text": "Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30504800", "endSection": "abstract" } ] }, { "body": "Which receptor does amantadine antagonize?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27642581" ], "ideal_answer": [ "Amantadine is an N-methyl-D-aspartic acid or N-methyl-D-aspartate (NMDA) receptor antagonist." ], "exact_answer": [ "NMDA" ], "type": "factoid", "id": "5e2dafccfbd6abf43b000013", "snippets": [ { "offsetInBeginSection": 116, "offsetInEndSection": 258, "text": "Amantadine is an N-methyl-D-aspartic acid or N-methyl-D-aspartate (NMDA) receptor antagonist that can be effective against postoperative pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27642581", "endSection": "abstract" } ] }, { "body": "Which characteristics are used in the SLEDAI index for SLE patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22800940", "http://www.ncbi.nlm.nih.gov/pubmed/17183620", "http://www.ncbi.nlm.nih.gov/pubmed/29688532", "http://www.ncbi.nlm.nih.gov/pubmed/1599520", "http://www.ncbi.nlm.nih.gov/pubmed/15468356" ], "ideal_answer": [ "The SLEDAi is a \"weighted\" index of 9 organ systems for disease activity in SLE which includes: 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic.", "Twenty-four variables were identified as important factors in a disease activity index. This generated a \"weighted\" index of 9 organ systems for disease activity in SLE, the SLEDAI 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic." ], "exact_answer": [ [ "central nervous system" ], [ "vascular system" ], [ "renal system" ], [ "musculoskeletal system" ], [ "serosal system" ], [ "dermal system" ], [ "immune system" ], [ "hematological system" ] ], "type": "list", "id": "5c7006037c78d6947100005d", "snippets": [ { "offsetInBeginSection": 284, "offsetInEndSection": 371, "text": "Twenty-four variables were identified as important factors in a disease activity index.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1599520", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1312, "text": "This generated a \"weighted\" index of 9 organ systems for disease activity in SLE, the SLEDAI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1599520", "endSection": "abstract" }, { "offsetInBeginSection": 1326, "offsetInEndSection": 1479, "text": "8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1599520", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 501, "text": "Patients with SLEDAI-2K renal, immunological and hematologic active descriptors were identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22800940", "endSection": "abstract" }, { "offsetInBeginSection": 1660, "offsetInEndSection": 2129, "text": "For the prediction of survival, AMS [hazard ratio (HR) = 1.16, p < 0.0001] and age at diagnosis (HR 1.05, p < 0.0001) were the only significant risk factors. For presence of damage, AMS (HR 1.06, p < 0.0001), age at diagnosis (HR 1.02, p = 0.0004), and disease duration (HR 1.05, p < 0.0001) were predictors. CAD was predicted by AMS (HR 1.12, p = 0.0003), male sex (HR 2.31, p = 0.02), age at diagnosis (HR 1.06, p < 0.0001), and disease duration (HR 1.10, p < 0.0001)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17183620", "endSection": "abstract" } ] }, { "body": "Which medication are included in the Polycap polypill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20334446", "http://www.ncbi.nlm.nih.gov/pubmed/20549577", "http://www.ncbi.nlm.nih.gov/pubmed/22189351", "http://www.ncbi.nlm.nih.gov/pubmed/22787067", "http://www.ncbi.nlm.nih.gov/pubmed/30342297", "http://www.ncbi.nlm.nih.gov/pubmed/19339045", "http://www.ncbi.nlm.nih.gov/pubmed/29540234" ], "ideal_answer": [ "Polycap polypil contains aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; and simvastatin, 20 mg. It is taken as two capsules once daily." ], "exact_answer": [ [ "aspirin" ], [ "atenolol" ], [ "ramipril" ], [ "thiazide" ], [ "simvastatin" ] ], "type": "list", "id": "5e2f992cfbd6abf43b000031", "snippets": [ { "offsetInBeginSection": 1053, "offsetInEndSection": 1246, "text": "Patients in the intervention arm will receive Polycap DS\u00ae (containing aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; simvastatin, 20 mg) taken as two capsules once daily. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29540234", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 856, "text": "This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30342297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "BACKGROUND: A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "BACKGROUND: The Polycap (polypill; aspirin [acetylsalicylic acid], ramipril, simvastatin, atenolol, and hydrochlorothiazide) was found to be safe and effective for reducing multiple cardiovascular risk factors in The Indian Polycap Study (TIPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334446", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 643, "text": "The Indian Polycap Study (TIPS) was the first to systematically test the clinical application of the polypill; it included ramipril, hydrochlorothiazide, atenolol, aspirin, and simvastatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20549577", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 983, "text": "METHODS: In a double-blind trial in 50 centres in India, 2053 individuals without cardiovascular disease, aged 45-80 years, and with one risk factor were randomly assigned, by a central secure website, to the Polycap (n=412) consisting of low doses of thiazide (12.5 mg), atenolol (50 mg), ramipril (5 mg), simvastatin (20 mg), and aspirin (100 mg) per day, or to eight other groups, each with about 200 individuals, of aspirin alone, simvastatin alone, hydrochlorthiazide alone, three combinations of the two blood-pressure-lowering drugs, three blood-pressure-lowering drugs alone, or three blood-pressure-lowering drugs plus aspirin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "BACKGROUND\n\nThe Polycap (polypill; aspirin [acetylsalicylic acid], ramipril, simvastatin, atenolol, and hydrochlorothiazide) was found to be safe and effective for reducing multiple cardiovascular risk factors in The Indian Polycap Study (TIPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20334446", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 644, "text": "The Indian Polycap Study (TIPS) was the first to systematically test the clinical application of the polypill; it included ramipril, hydrochlorothiazide, atenolol, aspirin, and simvastatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20549577", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 655, "text": "The Indian Polycap Study ( TIPS ) was the first to systematically test the clinical application of the polypill; it included ramipril , hydrochlorothiazide , atenolol , aspirin , and simvastatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20549577", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of Luspatercept.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30299326", "http://www.ncbi.nlm.nih.gov/pubmed/30285318", "http://www.ncbi.nlm.nih.gov/pubmed/28929587", "http://www.ncbi.nlm.nih.gov/pubmed/28870615", "http://www.ncbi.nlm.nih.gov/pubmed/30504333", "http://www.ncbi.nlm.nih.gov/pubmed/29499588", "http://www.ncbi.nlm.nih.gov/pubmed/30091846", "http://www.ncbi.nlm.nih.gov/pubmed/29193906", "http://www.ncbi.nlm.nih.gov/pubmed/29847322" ], "ideal_answer": [ "Luspatercept is a recombinant soluble activin type-II receptor-IgG-Fc fusion protein that blocks transforming growth factor beta (TGF b) superfamily inhibitors of erythropoiesis. Luspatercept is tested for the treatment of various types of anemias." ], "type": "summary", "id": "5e2903978b3851296d000007", "snippets": [ { "offsetInBeginSection": 92, "offsetInEndSection": 243, "text": "The method is a modification of a recently published protocol for Luspatercept (ACE-536, ACVR2B-Fc), another erythropoiesis stimulating fusion protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29193906", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 600, "text": "They are dimeric recombinant fusion proteins composed of the extracellular domain of a human activin receptor (ActRIIA or IIB) linked to the Fc part of human IgG1. Sotatercept (ActRIIA-Fc) and Luspatercept (a modified ActRIIB-Fc) in particular are now in phase 2/3 of clinical trials against anemia and included in the prohibited list established by the World Anti-Doping Agency. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29499588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "PURPOSE OF REVIEW: Sotatercept and luspatercept are recombinant soluble activin type-II receptor-IgG-Fc fusion proteins that are tested in clinical trials for the treatment of various types of anemias, including renal anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29847322", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 604, "text": "Other newly developed ESAs - luspatercept and sotatercept, both activin receptor type II-Fc fusion proteins (ActRII-Fc) - are also now prohibited and could be used in combination with rEPOs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30091846", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 742, "text": "Recently, activin inhibitors such as Luspatercept have shown to be effective in patients' refractory to ESAs and further clinical trials are ongoing to explore this further.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30299326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Combined detection of the ActRII-Fc fusion proteins Sotatercept (ActRIIA-Fc) and Luspatercept (modified ActRIIB-Fc) in serum by means of immunoaffinity purification, tryptic digestion, and LC-MS/MS.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285318", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 450, "text": "In particular, activin receptor competitors, such as the ActRII-Fc fusion proteins Sotatercept (ActRIIA-Fc) and Luspatercept (modified ActRIIB-Fc), have the potential for being misused as doping agents in sports as they were found to inhibit negative regulators of late-stage erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285318", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1457, "text": "An example is luspatercept, an activin-receptor trap that modifies transforming growth factor-\u03b2 signaling, thereby increasing the efficiency of erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30504333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF \u03b2) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28870615", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 283, "text": "Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF \u03b2) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28870615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Luspatercept (ACE-536, ACVR2B-Fc), a fusion protein consisting of the extracellular domain of ActRIIB receptor and the Fc-part of human immunoglobulin G1 (IgG1), is currently under clinical development (Phase III).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Sotatercept and luspatercept are recombinant soluble activin type-II receptor-IgG-Fc fusion proteins that are tested in clinical trials for the treatment of various types of anemias , including renal anemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29847322", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 283, "text": "Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF \u03b2) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28870615", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 553, "text": "Several antibody-based strategies for the detection of Luspatercept and other ACVR2B-Fc fusion proteins in human serum were evaluated (ELISA; IEF-, SDS-, and SAR-PAGE followed by Western blotting; immunoprecipitation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Luspatercept (ACE-536, ACVR2B-Fc), a fusion protein consisting of the extracellular domain of ActRIIB receptor and the Fc-part of human immunoglobulin G1 (IgG1), is currently under clinical development (Phase III).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929587", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "PURPOSE OF REVIEW\nSotatercept and luspatercept are recombinant soluble activin type-II receptor-IgG-Fc fusion proteins that are tested in clinical trials for the treatment of various types of anemias, including renal anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29847322", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 552, "text": "Several antibody-based strategies for the detection of Luspatercept and other ACVR2B-Fc fusion proteins in human serum were evaluated (ELISA; IEF-, SDS-, and SAR-PAGE followed by Western blotting; immunoprecipitation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28929587", "endSection": "abstract" } ] }, { "body": "Which method has been developed for mapping of Transcription Start Sites (TSS) starting from nanograms of RNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30404778" ], "ideal_answer": [ "SLIC-CAGE has been developed as a method to identify transcriptome-wide the binding sites of transcription start sites (TSSs) using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of DNA-binding proteins, transcription, individual nucleosomes and transcriptional starting sites.", "Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5' ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of the rules of transcription initiation, led to discovery of new core promoter sequence features, and discovered transcription initiation at enhancers genome-wide. SLIC-CAGE is a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA.", "SLIC-CAGE has been developed as a method to identify transcriptome-wide the binding sites of transcription start sites (TSSs) using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of DNA-binding sites, transcription, mRNA, and nucleosomes." ], "exact_answer": [ "SLIC-CAGE" ], "type": "factoid", "id": "5e2deb35fbd6abf43b00001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1241, "text": "Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5' ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of the rules of transcription initiation, led to discovery of new core promoter sequence features, and discovered transcription initiation at enhancers genome-wide. The biggest limitation of CAGE is that even the most recently improved version (nAnT-iCAGE) still requires large amounts of total cellular RNA (5 \u00b5g), preventing its application to scarce biological samples such as those from early embryonic development or rare cell types. Here, we present SLIC-CAGE, a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods, by generating a complex, high-quality library from mouse embryonic day 11.5 primordial germ cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "abstract" } ] }, { "body": "What are the molecular and cellular effects of LB-100 on ovarian carcinoma cells following cisplatin treatment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25376608" ], "ideal_answer": [ "LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and gH2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites." ], "type": "summary", "id": "5e29fc57aa19d74431000006", "snippets": [ { "offsetInBeginSection": 817, "offsetInEndSection": 1347, "text": "LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and \u03b3H2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376608", "endSection": "abstract" }, { "offsetInBeginSection": 1499, "offsetInEndSection": 1666, "text": "Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25376608", "endSection": "abstract" } ] }, { "body": "Can LB-100 downregulate miR-33?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28588271" ], "ideal_answer": [ "No, LB-100 has been reported to modulate (upregulate) only miR-181b-1." ], "exact_answer": "no", "type": "yesno", "id": "5e2a04feaa19d74431000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28588271", "endSection": "title" }, { "offsetInBeginSection": 683, "offsetInEndSection": 989, "text": "LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3' untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28588271", "endSection": "abstract" } ] }, { "body": "What is molecular radiotherapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28747518", "http://www.ncbi.nlm.nih.gov/pubmed/29043399" ], "ideal_answer": [ "Molecular radiotherapy is working through tumor-targeted radionuclides." ], "exact_answer": [ "Molecular radiotherapy is working through tumor-targeted radionuclides." ], "type": "factoid", "id": "5e499c636d0a27794100000a", "snippets": [ { "offsetInBeginSection": 311, "offsetInEndSection": 405, "text": "Molecular radiotherapy with tumor-targeted radionuclides may overcome some of these challenges", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28747518", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 437, "text": "Neuroblastoma may be treated with molecular radiotherapy, 131I meta-Iodobenzylguanidine and 177Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29043399", "endSection": "abstract" } ] }, { "body": "Which mRNAs are sequestered in stress granules?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29576526", "http://www.ncbi.nlm.nih.gov/pubmed/24013423", "http://www.ncbi.nlm.nih.gov/pubmed/29483269", "http://www.ncbi.nlm.nih.gov/pubmed/21118122", "http://www.ncbi.nlm.nih.gov/pubmed/29129640" ], "ideal_answer": [ "Stress granules are higher order assemblies of nontranslating mRNAs and proteins that form when translation initiation is inhibited. \nThis subset of mRNAs is characterized by extended length and adenylate-uridylate (AU)-rich motifs, is highly enriched with genes critical for cell survival and proliferation. mRNA accumulation in stress granules correlates with longer coding and UTR regions and poor translatability" ], "exact_answer": [ "long, AU-rich and non-ribosome associating mRNA" ], "type": "factoid", "id": "5c74305d7c78d694710000a4", "snippets": [ { "offsetInBeginSection": 440, "offsetInEndSection": 585, "text": "short deletions affecting nuclear localization signal (NLS) and causing cytoplasmic mislocalization can be sequestered into stress granules (SGs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013423", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 796, "text": " By using a series of chimaeric transcripts, we have demonstrated that transcript localization at the endoplasmic reticulum bypasses the signals dictating stress granule sequestration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Stress granules are higher order assemblies of nontranslating mRNAs and proteins that form when translation initiation is inhibited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29483269", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 304, "text": "Partially due to the belief that translationally suppressed mRNAs are recruited to SGs in bulk, stress-induced dynamic redistribution of mRNA has not been thoroughly characterized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29576526", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 633, "text": "This subset, characterized by extended length and adenylate-uridylate (AU)-rich motifs, is highly enriched with genes critical for cell survival and proliferation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29576526", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 669, "text": "mRNA accumulation in stress granules correlates with longer coding and UTR regions and poor translatability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29129640", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1151, "text": "These results suggest that stress granules may not represent a specific biological program of messenger ribonucleoprotein (mRNP) assembly, but instead form by condensation of nontranslating mRNPs in proportion to their length and lack of association with ribosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29129640", "endSection": "abstract" } ] }, { "body": "Which are the problems associated with the use of PD-L1 as immunotherapy biomarker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30487198", "http://www.ncbi.nlm.nih.gov/pubmed/28472902", "http://www.ncbi.nlm.nih.gov/pubmed/28837143", "http://www.ncbi.nlm.nih.gov/pubmed/30393621", "http://www.ncbi.nlm.nih.gov/pubmed/25695955", "http://www.ncbi.nlm.nih.gov/pubmed/27532023", "http://www.ncbi.nlm.nih.gov/pubmed/26927720", "http://www.ncbi.nlm.nih.gov/pubmed/26778219", "http://www.ncbi.nlm.nih.gov/pubmed/29387716", "http://www.ncbi.nlm.nih.gov/pubmed/27801734", "http://www.ncbi.nlm.nih.gov/pubmed/30419350", "http://www.ncbi.nlm.nih.gov/pubmed/26516064", "http://www.ncbi.nlm.nih.gov/pubmed/26973128", "http://www.ncbi.nlm.nih.gov/pubmed/26501438", "http://www.ncbi.nlm.nih.gov/pubmed/29567557", "http://www.ncbi.nlm.nih.gov/pubmed/28881780", "http://www.ncbi.nlm.nih.gov/pubmed/27229745" ], "ideal_answer": [ "The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells", "The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells." ], "exact_answer": [ [ "low levels of expression" ], [ "variable detection antibodies" ], [ "tissue preparation problems" ], [ "source of expression" ], [ "staining of tumor cells" ], [ "immunohistochemistry cutoffs" ] ], "type": "list", "id": "5c7a4a31d774d04240000006", "snippets": [ { "offsetInBeginSection": 342, "offsetInEndSection": 610, "text": "PD-L1 expression has shown a positive association with response to PD-1 inhibition in noncentral nervous system (CNS) tumors, e.g., melanoma or non-small cell lung cancer, and is discussed as a potential predictive biomarker for patient selection in these tumor types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26501438", "endSection": "abstract" }, { "offsetInBeginSection": 1523, "offsetInEndSection": 1875, "text": " In summary, the ongoing clinical studies evaluating the activity of PD-1/PD-L1 inhibitors in glioblastoma need to be complemented with well designed and stringently executed studies to understand the influence of PD-1/PD-L1 expression on therapy response or failure and to develop robust means of PD-L1 assessment for meaningful biomarker development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26501438", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1297, "text": "Emerging data suggest that patients whose tumors overexpress PD-L1 by IHC have improved clinical outcomes with anti-PD-1-directed therapy, but the presence of robust responses in some patients with low levels of expression of these markers complicates the issue of PD-L1 as an exclusionary predictive biomarker. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25695955", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 983, "text": "The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25695955", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 209, "text": "it is not clear whether expression of the ligand PD-L1 is a biomarker for response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26516064", "endSection": "abstract" }, { "offsetInBeginSection": 1501, "offsetInEndSection": 1781, "text": "\u00a0In conclusion, while PD-L1 expression is often a predictive factor for treatment response, it must be complemented by other biomarkers or histopathologic\u00a0features,\u00a0such as the composition\u00a0and\u00a0amount\u00a0of inflammatory cells in the tumor microenvironment and their functional status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27229745", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1242, "text": "PD-L1 expression is likely an imperfect predictive biomarker for patient selection and association with other markers of the tumor immune microenvironment will be probably necessary in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26778219", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 843, "text": "Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26973128", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 916, "text": "Despite impressive treatment outcomes in a subset of patients who receive these immune therapies, many patients with NSCLC fail to respond to anti-PD-1/PD-L1 and the identification of a biomarker to select these patients remains highly sought after. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27532023", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1283, "text": "However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01-1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy. These data need to be confirmed by larger studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29387716", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 222, "text": ". Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28472902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28881780", "endSection": "title" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1400, "text": "In summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28881780", "endSection": "abstract" }, { "offsetInBeginSection": 1799, "offsetInEndSection": 1938, "text": "Here we demonstrate that PD-L1 is currently the best-known biomarker for G3 NENs, becoming the new gold standard for G3 NEN discrimination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28837143", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1276, "text": "Thus, sPD-L1 levels are increased in melanoma patients with severe OSA and, in addition, might serve as a potential biomarker of CM aggressiveness and invasiveness in this group of subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30487198", "endSection": "abstract" }, { "offsetInBeginSection": 467, "offsetInEndSection": 901, "text": "Programmed cell death ligand-1 (PD-L1), which is a validated biomarker in non-small cell lung cancer (NSCLC), is often also used to select patients for CIT in the context of gastroesophageal cancer, although this marker has not been validated for this purpose. We question the use of PD-L1 as a biomarker in gastroesophageal cancers, as there are fundamental differences in PD-L1 expression between NSCLC and gastroesophageal cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30419350", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 854, "text": "PD-L1 expression as a predictive biomarker for immunotherapy in NSCLC patients has shown some value for predicting response to immune checkpoint inhibitors in some studies, but not in others, and its use has been complicated by a number of factors which has prompted many researchers to establish better predictive biomarkers for immunotherapy of NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30393621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Breaking the biomarker code: PD-L1 expression and checkpoint inhibition in advanced NSCLC.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29567557", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "PD-L1 Expression in Carcinosarcomas of the Gynecologic Tract: A Potentially Actionable Biomarker.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27801734", "endSection": "title" }, { "offsetInBeginSection": 442, "offsetInEndSection": 608, "text": "Programmed death-ligand 1 (PD-L1) has emerged as a potential target for therapeutics in a number of malignant tumors, including melanoma, lung, and colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27801734", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 763, "text": "This is becoming a much debated issue, and the immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one possible biomarker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927720", "endSection": "abstract" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1188, "text": "Given that there are 4 such drugs rapidly approaching regulatory approval, each with its own independent PD-L1 immunohistochemistry biomarker test, both oncologists and pathologists face some significant challenges.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927720", "endSection": "abstract" } ] }, { "body": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23850259" ], "ideal_answer": [ "Yes. Poliosis circumscripta is another term for a white or unpigmented patch of hair or skin.", "Yes, poliosis circumscripta, or \"white forelock,\" is defined as a localized patch of white hair in a group of hair follicles.", "poliosis circumscripta is a \" localized patch of white hair in a group of hair foll white forelock \" circumscripta was defined as a \"", "yes, \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle", "Yes, poliosis circumscripta is another term for a white or unpigmented patch of hair or skin.", "\"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle", "white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle" ], "exact_answer": "yes", "type": "yesno", "id": "5e41620648dab47f2600000e", "snippets": [ { "offsetInBeginSection": 32, "offsetInEndSection": 144, "text": "\"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23850259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23850259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Although traditionally known as \" white forelock , \" poliosis circumscripta , defined as a localized patch of white hair in a group of hair follicles , can involve any hairy area on the body including the scalp , eyebrows , and eyelashes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23850259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23850259", "endSection": "abstract" } ] }, { "body": "How are SAHFS created?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17579878", "http://www.ncbi.nlm.nih.gov/pubmed/23964094", "http://www.ncbi.nlm.nih.gov/pubmed/17158953", "http://www.ncbi.nlm.nih.gov/pubmed/22795131", "http://www.ncbi.nlm.nih.gov/pubmed/24006061", "http://www.ncbi.nlm.nih.gov/pubmed/16901784", "http://www.ncbi.nlm.nih.gov/pubmed/23232545" ], "ideal_answer": [ "Cellular senescence-associated heterochromatic foci (SAHFS) are a novel type of chromatin condensation involving alterations of linker histone H1 and linker DNA-binding proteins. SAHFS can be formed by a variety of cell types, but their mechanism of action remains unclear.", "Senescent cells have a distinct gene expression profile, which is often accompanied by the spatial redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs). Their creation goes through the senescence stimulated depletion of LMNB1, which facilitates the nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers which characterize senescence-associated heterochromatic foci (SAHF)." ], "type": "summary", "id": "5d35ef8a7bc3fee31f000002", "snippets": [ { "offsetInBeginSection": 248, "offsetInEndSection": 567, "text": "These include measurement of senescence-associated \u03b2-galactosidase activity (SA-\u03b2-gal), senescence-associated heterochromatin foci (SAHFs), proliferative arrest, morphological changes, and expression and activity of proteins involved in the senescence process, such as p53 and Rb pathway proteins and secretory proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24006061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964094", "endSection": "title" }, { "offsetInBeginSection": 66, "offsetInEndSection": 254, "text": "Senescent cells have a distinct gene expression profile, which is often accompanied by the spatial redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964094", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 858, "text": " Genome-wide mapping reveals that LMNB1 is depleted during senescence, preferentially from the central regions of lamina-associated domains (LADs), which are enriched for Lys9 trimethylation on histone H3 (H3K9me3). LMNB1 knockdown facilitates the spatial relocalization of perinuclear H3K9me3-positive heterochromatin, thus promoting SAHF formation, which could be inhibited by ectopic LMNB1 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23964094", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 407, "text": "nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22795131", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1182, "text": "Alterations of chromatin structure are believed to contribute to the irreversible nature of the senescent state. Senescent cells form characteristic heterochromatin structure called senescence-associated heterochromatic foci (SAHFs), which may repress the expression of proliferation-promoting genes, such as E2F target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17579878", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 604, "text": "urprisingly, we show that the High-Mobility Group A (HMGA) proteins, which can promote tumorigenesis, accumulate on the chromatin of senescent fibroblasts and are essential structural components of SAHFs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16901784", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 591, "text": "Remarkably, SAHF-positive senescent cells lose linker histone H1 and exhibit increased levels of chromatin-bound high mobility group A2 (HMGA2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Cellular senescence is a tumor-suppressing mechanism that is accompanied by characteristic chromatin condensation called senescence-associated heterochromatic foci (SAHFs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17158953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "It is almost ten years since senescence associated heterochromatic foci (SAHFs) were first described in human diploid fibroblasts (HDFs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23232545", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1421, "text": "Thus the layered HOCS of SAHFs is likely achieved mainly through the spatial rearrangement of pre-existing heterochromatin, rather than spreading of heterochromatin. Evidence for the co-association of similar types of chromatin is emerging and SAHFs may provide a unique model system to study the correlation between HOCS and chromatin types, which are readily visible and regulable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23232545", "endSection": "abstract" } ] }, { "body": "What is another name for AZD0530?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23144237" ], "ideal_answer": [ "AZD0530 is also known as saracatinib." ], "exact_answer": [ "Saracatinib" ], "type": "factoid", "id": "5e540c866d0a277941000052", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144237", "endSection": "title" }, { "offsetInBeginSection": 459, "offsetInEndSection": 655, "text": "We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144237", "endSection": "abstract" } ] }, { "body": "Which is the effect of the HP1a protein on chromatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27838630", "http://www.ncbi.nlm.nih.gov/pubmed/19798443", "http://www.ncbi.nlm.nih.gov/pubmed/17875665", "http://www.ncbi.nlm.nih.gov/pubmed/22547675", "http://www.ncbi.nlm.nih.gov/pubmed/24555990", "http://www.ncbi.nlm.nih.gov/pubmed/30384843", "http://www.ncbi.nlm.nih.gov/pubmed/22761891", "http://www.ncbi.nlm.nih.gov/pubmed/23166515", "http://www.ncbi.nlm.nih.gov/pubmed/24990964", "http://www.ncbi.nlm.nih.gov/pubmed/23028361", "http://www.ncbi.nlm.nih.gov/pubmed/29986897" ], "ideal_answer": [ "Heterochromatin Protein 1 (HP1a) is a well-known conserved protein that is involved in heterochromatin formation and gene silencing through the reading of the heterochromatin mark methylation of histone H3 lysine 9 (H3K9me) in different species including humans.", "Heterochromatin-associated protein 1 (HP1a) mediates silencing and switching at the mating-type loci and is essential for pluripotency in Drosophila. HP1a belongs to a homologous family of histone-deacetyltransferases that mediate chromatin organization through the binding of histones to chromatin. The ATP-dependent chromatin-remodelling activity of HP1A is mediated, in part, by its interaction with histone H3 methyltransferase 3 (H3K9me2/3)." ], "exact_answer": [ "heterochromatic gene silencing" ], "type": "factoid", "id": "5d35f1267bc3fee31f000004", "snippets": [ { "offsetInBeginSection": 524, "offsetInEndSection": 761, "text": "Here we show that PIWI, an ARGONAUTE/PIWI protein family member that binds to Piwi-interacting RNAs (piRNAs), strongly and specifically interacts with heterochromatin protein 1a (HP1a), a central player in heterochromatic gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17875665", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Heterochromatin protein 1 (HP1a) positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19798443", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Heterochromatin Protein 1 (HP1a) is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19798443", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1250, "text": "HP1a is associated with transcripts of more than one hundred euchromatic genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19798443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Heterochromatin protein 1 (HP1) proteins, recognized readers of the heterochromatin mark methylation of histone H3 lysine 9 (H3K9me), are important regulators of heterochromatin-mediated gene silencing and chromosome structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166515", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 342, "text": "heterochromatin protein 1a (HP1a).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22547675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "HP1a targets the Drosophila KDM4A demethylase to a subset of heterochromatic genes to regulate H3K36me3 levels.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22761891", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028361", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "HP1a: a structural chromosomal protein regulating transcription.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555990", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Heterochromatin protein 1 (HP1a in Drosophila) is a conserved eukaryotic chromosomal protein that is prominently associated with pericentric heterochromatin and mediates the concomitant gene silencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Heterochromatin-associated interactions of Drosophila HP1a with dADD1, HIPP1, and repetitive RNAs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990964", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Heterochromatin protein 1 (HP1a) has conserved roles in gene silencing and heterochromatin and is also implicated in transcription, DNA replication, and repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Maintenance of Heterochromatin by the Large Subunit of the CAF-1 Replication-Coupled Histone Chaperone Requires Its Interaction with HP1a Through a Conserved Motif.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27838630", "endSection": "title" }, { "offsetInBeginSection": 357, "offsetInEndSection": 628, "text": "The chromatin assembly factor 1 (CAF-1) is involved in the assembly of H3-H4 histone dimers on newly synthesized DNA and in the maintenance of a higher order structure, the heterochromatin, through an interaction of its large subunit with the heterochromatin protein HP1a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27838630", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1115, "text": "As expected, active gene promoters are mostly not present in LADs, HP1a and Pc domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30384843", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 914, "text": "Finally, we find that HP1a also specifies initiation sites of nuclear envelope reassembly on undamaged chromatin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29986897", "endSection": "abstract" } ] }, { "body": "Is Selumetinib effective for low-grade glioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "http://www.ncbi.nlm.nih.gov/pubmed/28339824" ], "ideal_answer": [ "Selumetinib has promising antitumor activity in children with LGG." ], "exact_answer": "yes", "type": "yesno", "id": "5e44bdba48dab47f2600001c", "snippets": [ { "offsetInBeginSection": 1651, "offsetInEndSection": 1729, "text": "Conclusion: Selumetinib has promising antitumor activity in children with LGG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28339824", "endSection": "abstract" }, { "offsetInBeginSection": 2793, "offsetInEndSection": 2976, "text": "INTERPRETATION\n\nSelumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 2977, "offsetInEndSection": 3319, "text": "These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 1651, "offsetInEndSection": 1728, "text": "Conclusion Selumetinib has promising antitumor activity in children with LGG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28339824", "endSection": "abstract" }, { "offsetInBeginSection": 2745, "offsetInEndSection": 2927, "text": "INTERPRETATION Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 1657, "offsetInEndSection": 1735, "text": "Conclusion\n\nSelumetinib has promising antitumor activity in children with LGG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28339824", "endSection": "abstract" }, { "offsetInBeginSection": 2749, "offsetInEndSection": 2932, "text": "INTERPRETATION\nSelumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 2932, "offsetInEndSection": 3275, "text": "These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 2099, "offsetInEndSection": 2441, "text": "These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 1915, "offsetInEndSection": 2098, "text": "INTERPRETATION: Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 2715, "offsetInEndSection": 2882, "text": "Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" }, { "offsetInBeginSection": 2883, "offsetInEndSection": 3225, "text": "These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31151904", "endSection": "abstract" } ] }, { "body": "What is Nextflow?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29412134" ], "ideal_answer": [ "Reproducing routine bioinformatics analysis is challenging owing to a combination of factors hard to control for. Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines. Third party pipelines can be ported into Nextflow with minimum re-coding.", "Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines.", "Reproducing routine bioinformatics analysis is challenging owing to a combination of factors hard to control for. Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines.", "Nextflow is a flow management framework that uses container technology to ensure efficient deployment and reproducibility of computational analysis pipelines." ], "type": "summary", "id": "5e501d866d0a277941000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 547, "text": "Reproducing routine bioinformatics analysis is challenging owing to a combination of factors hard to control for. Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines. Third party pipelines can be ported into Nextflow with minimum re-coding. We used RNA-Seq quantification, genome annotation and phylogeny reconstruction examples to show how two seemingly irreproducible analyzes can be made stable across platforms when ported into Nextflow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29412134", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 91, "text": "Nextflow, an efficient tool to improve computation numerical stability in genomic analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29412134", "endSection": "title" }, { "offsetInBeginSection": 114, "offsetInEndSection": 272, "text": "Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29412134", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 275, "text": "Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29412134", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 273, "text": "Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29412134", "endSection": "abstract" } ] }, { "body": "Which application is the backbone of BioPAXViz?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28453679" ], "ideal_answer": [ "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAZViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny.", "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAXViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny. Furthermore, BioPAXViz supports the display of hierarchical trees that allow efficient navigation through sets of variants of a single reference pathway. Thus, BioPAXViz can significantly facilitate, and contribute to, the study of metabolic pathway evolution and engineering.", "BioPAXViz is a Cytoscape (version 3) application providing a comprehensive framework for metabolic pathway visualization. The application provides a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny.", "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization.", "BioPAXViz is a Cytoscape (version 3) application providing a comprehensive framework for metabolic pathway visualization.", "BioPAXViz is a Cytoscape (version 3) application for the visual exploration of metabolic pathway evolution. The software is distributed under the MIT License and is accompanied by example files and data. Additional documentation is available at the aforementioned repository.", "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAXViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny.", "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAXViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny. Furthermore, BioPAXViz supports the display of hierarchical trees that allow efficient navigation through sets of variants of a single reference pathway. Thus, BioPAXViz can significantly facilitate, and contribute to, the study of metabolic pathway evolution and engineering.Availability and Implementation: BioPAXViz has been developed as a Cytoscape app and is available at: https://github.com/CGU-CERTH/BioPAX.Viz." ], "exact_answer": [ "Cytoscape (version 3)" ], "type": "factoid", "id": "5e4adb486d0a277941000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "BioPAXViz: a cytoscape application for the visual exploration of metabolic pathway evolution.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 794, "text": "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAXViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny. Furthermore, BioPAXViz supports the display of hierarchical trees that allow efficient navigation through sets of variants of a single reference pathway. Thus, BioPAXViz can significantly facilitate, and contribute to, the study of metabolic pathway evolution and engineering.Availability and Implementation: BioPAXViz has been developed as a Cytoscape app and is available at: https://github.com/CGU-CERTH/BioPAX.Viz.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Summary\n\nBioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Summary BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 793, "text": "Availability and Implementation BioPAXViz has been developed as a Cytoscape app and is available at: https://github.com/CGU-CERTH/BioPAX.Viz.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BioPAXViz is a Cytoscape ( version 3 ) application , providing a comprehensive framework for metabolic pathway visualization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "BioPAXViz: a cytoscape application for the visual exploration of metabolic pathway evolution", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Summary\nBioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Summary: BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" }, { "offsetInBeginSection": 644, "offsetInEndSection": 753, "text": "BioPAXViz has been developed as a Cytoscape app and is available at: https://github.com/CGU-CERTH/BioPAX.Viz.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28453679", "endSection": "abstract" } ] }, { "body": "What is SpatialDE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29553579" ], "ideal_answer": [ "SpatialDE is a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data. SpatialDE also implements ' automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology.", "Technological advances have made it possible to measure spatially resolved gene expression at high throughput. However, methods to analyze these data are not established. SpatialDE is a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data. SpatialDE also implements 'automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology." ], "type": "summary", "id": "5e51a7ec6d0a27794100003b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "SpatialDE: identification of spatially variable genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553579", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 481, "text": "Technological advances have made it possible to measure spatially resolved gene expression at high throughput. However, methods to analyze these data are not established. Here we describe SpatialDE, a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data. SpatialDE also implements 'automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553579", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 481, "text": "SpatialDE also implements 'automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553579", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 338, "text": "Here we describe SpatialDE, a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553579", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 343, "text": "Here we describe SpatialDE , a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553579", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 482, "text": "SpatialDE also implements 'automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553579", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 339, "text": "Here we describe SpatialDE, a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553579", "endSection": "abstract" } ] }, { "body": "What is the Match BAM to VCF method?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28186259" ], "ideal_answer": [ "MBV (Match BAM to VCF) is a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "Large genomic datasets combining genotype and sequence data, such as for expression quantitative trait loci (eQTL) detection, require perfect matching between both data types. MBV (Match BAM to VCF) is a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias. MBV is implemented in C ++ as an independent component of the QTLtools software package, the binary and source codes are freely available at https://qtltools.github.io/qtltools/." ], "type": "summary", "id": "5e3356c0fbd6abf43b00005c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "MBV: a method to solve sample mislabeling and detect technical bias in large combined genotype and sequencing assay datasets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 560, "text": "Large genomic datasets combining genotype and sequence data, such as for expression quantitative trait loci (eQTL) detection, require perfect matching between both data types.Results: We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.Availability and Implementation: MBV is implemented in C\u2009++\u2009as an independent component of the QTLtools software package, the binary and source codes are freely available at https://qtltools.github.io/qtltools/ .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 350, "text": "Results\n\nWe described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 347, "text": "Results We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 350, "text": "Results\nWe described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 714, "text": "Motivation: Large genomic datasets combining genotype and sequence data, such as for expression quantitative trait loci (eQTL) detection, require perfect matching between both data types.Results: We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.Availability and Implementation: MBV is implemented in C\u2009++\u2009as an independent component of the QTLtools software package, the binary and source codes are freely available at https://qtltools.github.io/qtltools/ .Contact: olivier.delaneau@unige.ch or emmanouil.dermitzakis@unige.ch.Supplementary information: Supplementary data are available at Bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 328, "text": "We described here MBV (Match BAM to VCF); a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28186259", "endSection": "abstract" } ] }, { "body": "Describe MAGNIMS criteria.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28235075", "http://www.ncbi.nlm.nih.gov/pubmed/29856160", "http://www.ncbi.nlm.nih.gov/pubmed/30169254", "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "http://www.ncbi.nlm.nih.gov/pubmed/28093711", "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "http://www.ncbi.nlm.nih.gov/pubmed/27600111", "http://www.ncbi.nlm.nih.gov/pubmed/30915227" ], "ideal_answer": [ "Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS)." ], "type": "summary", "id": "5e48b397d14c9f295d000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "OBJECTIVES: We compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for dissemination in space (DIS) in predicting the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1425, "text": "CONCLUSION: 2016 MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher sensitivity but lower specificity than 2010 McDonald criteria in predicting conversion to CDMS in CIS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "BACKGROUND: In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Applicability of McDonald 2010 and Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) 2016 Magnetic Resonance Imaging Criteria for the Diagnosis of Multiple Sclerosis in Sri Lanka.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856160", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "BACKGROUND AND PURPOSE: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) group recently proposed guidelines to replace the existing dissemination-in-space criteria in McDonald 2010 magnetic resonance imaging (MRI) criteria for diagnosing multiple sclerosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856160", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1135, "text": "Performance of the 2001, 2010, and 2017 international McDonald criteria for the diagnosis of multiple sclerosis, the 2016 MRI in multiple sclerosis (MAGNIMS) criteria, and our 2011 proposed (Verhey) criteria were determined; performance was adjudicated with generalised linear models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169254", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 550, "text": " While \u2a7e1 periventricular lesion is included in the 2010 DIS criteria, earlier McDonald criteria required \u2a7e3 periventricular lesions to confirm DIS and recent Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS)-recommended DIS criteria also require \u2a7e3 lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600111", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 620, "text": "Therefore, in the most recent MRI criteria for the diagnosis of MS (MAGNIMS consensus guidelines), neurophysiological confirmation of optic nerve dysfunction (slowed conduction on visual EP), support dissemination in space and, in patients without concurrent visual symptoms, dissemination in time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28093711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Reliability of cortical lesion detection on double inversion recovery MRI applying the MAGNIMS-Criteria in multiple sclerosis patients within a 16-months period.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28235075", "endSection": "title" }, { "offsetInBeginSection": 163, "offsetInEndSection": 320, "text": "We sought to evaluate the reliability of CL detection on DIR longitudinally at multiple subsequent time-points applying the MAGNIMs scoring criteria for CLs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28235075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "BACKGROUND\n\nIn 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Evaluation of 2016 MAGNIMS MRI criteria for dissemination in space in patients with a clinically isolated syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "OBJECTIVES\n\nWe compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for dissemination in space (DIS) in predicting the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "BACKGROUND AND PURPOSE\n\nThe magnetic resonance imaging in multiple sclerosis (MAGNIMS) group recently proposed guidelines to replace the existing dissemination-in-space criteria in McDonald 2010 magnetic resonance imaging (MRI) criteria for diagnosing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856160", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 319, "text": "We sought to evaluate the reliability of CL detection on DIR longitudinally at multiple subsequent time-points applying the MAGNIMs scoring criteria for CLs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28235075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "In 2016 , the Magnetic Resonance Imaging in Multiple Sclerosis ( MAGNIMS ) network proposed modifications to the MRI criteria to define dissemination in space ( DIS ) and time ( DIT ) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome ( CIS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Evaluation of 2016 MAGNIMS MRI criteria for dissemination in space in patients with a clinically isolated syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "We compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis ( MAGNIMS ) criteria for dissemination in space ( DIS ) in predicting the conversion to clinically definite multiple sclerosis ( CDMS ) in patients with clinically isolated syndrome ( CIS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "OBJECTIVES\nWe compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for dissemination in space (DIS) in predicting the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1431, "text": "CONCLUSION\n2016 MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher sensitivity but lower specificity than 2010 McDonald criteria in predicting conversion to CDMS in CIS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "BACKGROUND AND PURPOSE\nThe magnetic resonance imaging in multiple sclerosis (MAGNIMS) group recently proposed guidelines to replace the existing dissemination-in-space criteria in McDonald 2010 magnetic resonance imaging (MRI) criteria for diagnosing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "BACKGROUND\nIn 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "endSection": "abstract" }, { "offsetInBeginSection": 2034, "offsetInEndSection": 2315, "text": "At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0\u00b791 [95% CI 0\u00b785-0\u00b794] and 2016 MAGNIMS 0\u00b793 [0\u00b788-0\u00b796]), similar specificity (0\u00b733 [0\u00b725-0\u00b742] and 0\u00b732 [0\u00b724-0\u00b741]), and similar area under the curve values (AUC; 0\u00b762 [0\u00b757-0\u00b767] and 0\u00b763 [0\u00b758-0\u00b767]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 550, "text": "While \u2a7e1 periventricular lesion is included in the 2010 DIS criteria, earlier McDonald criteria required \u2a7e3 periventricular lesions to confirm DIS and recent Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS)-recommended DIS criteria also require \u2a7e3 lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600111", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 271, "text": "PURPOSE: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) group recently proposed guidelines to replace the existing dissemination-in-space criteria in McDonald 2010 magnetic resonance imaging (MRI) criteria for diagnosing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "We compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for dissemination in space (DIS) in predicting the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1386, "text": "2016 MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher sensitivity but lower specificity than 2010 McDonald criteria in predicting conversion to CDMS in CIS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28492101", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 511, "text": "To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30915227", "endSection": "abstract" }, { "offsetInBeginSection": 1118, "offsetInEndSection": 1309, "text": "For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1-93.2%) versus 100% (84.6-100%); specificity 72.7% (49.8-89.3%) versus 25.6% (13.0-42.1%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30915227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "The magnetic resonance imaging in multiple sclerosis (MAGNIMS) group recently proposed guidelines to replace the existing dissemination-in-space criteria in McDonald 2010 magnetic resonance imaging (MRI) criteria for diagnosing multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29275979", "endSection": "abstract" } ] }, { "body": "Is SATB1 expressed in thymocytes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27454343", "http://www.ncbi.nlm.nih.gov/pubmed/15814699", "http://www.ncbi.nlm.nih.gov/pubmed/12692553", "http://www.ncbi.nlm.nih.gov/pubmed/9340009", "http://www.ncbi.nlm.nih.gov/pubmed/9886398" ], "ideal_answer": [ "A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes. SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. In this study we show that special AT-rich binding protein 1 (SATB1), a T lineage-enriched chromatin organizer and regulator, is induced in response to TCR signaling during early thymocyte development", "Yes, SATB1 is expressed in thymocytes and has a major role in the regulation of cell differentiation.", "yes, This was shown by fluorescence in situ hybridization on wild-type and Satb1-null thymocytes using in vivo SATB1-bound sequences as probes. ", "SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. ", "SATB1 is a homeodomain protein and is predominantly expressed in thymocytes.", "SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. SATB1 is a cell-type specific nuclear protein that recruits chromatin-remodeling factors and regulates numerous genes during thymocyte differentiation.", "A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes." ], "exact_answer": "yes", "type": "yesno", "id": "5d35c227b3a6380763000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9340009", "endSection": "title" }, { "offsetInBeginSection": 261, "offsetInEndSection": 338, "text": "SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9340009", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 313, "text": "SATB1 is a cell-type specific nuclear protein that recruits chromatin-remodeling factors and regulates numerous genes during thymocyte differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12692553", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 636, "text": " This was shown by fluorescence in situ hybridization on wild-type and Satb1-null thymocytes using in vivo SATB1-bound sequences as probes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12692553", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1175, "text": "By contrast, in Satb1-null thymocytes, this site is marked by methylation at H3 Lys9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12692553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Regulation of SATB1 during thymocyte development by TCR signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27454343", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 451, "text": "In this study we show that special AT-rich binding protein 1 (SATB1), a T lineage-enriched chromatin organizer and regulator, is induced in response to TCR signaling during early thymocyte development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27454343", "endSection": "abstract" }, { "offsetInBeginSection": 453, "offsetInEndSection": 590, "text": "SATB1 expression profile coincides with T lineage commitment and upregulation of SATB1 correlates with positive selection of thymocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27454343", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 910, "text": " We also demonstrate that GATA3, the key transcriptional regulator of \u03b1\u03b2 T cells positively regulates SATB1 expression in thymocytes suggesting an important role for SATB1 during T cell development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27454343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "High level expression of the Xlr nuclear protein in immature thymocytes and colocalization with the matrix-associated region-binding SATB1 protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886398", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "A role for SATB1, a nuclear matrix association region-binding protein, in the development of CD8SP thymocytes and peripheral T lymphocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15814699", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 531, "text": "Because homozygous SATB1-null mice do not survive to adulthood due to non-thymus autonomous defects, mice were produced that were homozygous for a T cell-specific SATB1-antisense transgene and heterozygous for a SATB1-null allele.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15814699", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 735, "text": "Thymic SATB1 protein was reduced significantly in these mice, and the major cellular phenotype observed was a significant reduction in the percentage of CD8SP T cells in thymus, spleen, and lymph nodes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15814699", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1199, "text": "The reduction in thymic SATB1 does not lead to the variegated expression of CD8-negative single positive thymocytes seen upon deletion of several regulatory elements and suggested by others to reflect failure to activate the CD8 locus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15814699", "endSection": "abstract" } ] }, { "body": "Which company produces ORMD-0801?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23593142" ], "ideal_answer": [ "ORMD-0801 is produced by Oramed Pharmaceuticals." ], "exact_answer": [ "Oramed Pharmaceuticals" ], "type": "factoid", "id": "5e763602c6a8763d2300000c", "snippets": [ { "offsetInBeginSection": 393, "offsetInEndSection": 606, "text": "In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin) in addressing this resistant clinical state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593142", "endSection": "abstract" } ] }, { "body": "In which cell organelle is the SAF-A protein localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10933876", "http://www.ncbi.nlm.nih.gov/pubmed/19556781", "http://www.ncbi.nlm.nih.gov/pubmed/22162999" ], "ideal_answer": [ "saf-a/hnrnp u is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region dna", "SAF-A/hnRNP U is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region DNA (MAR) and RNA as a component of hnRNPs. Scaffold attachment factor A (SAF-A) participates in the regulation of gene expression by organizing chromatin into transcriptionally active domains and by interacting directly with RNA polymerase II.", "Scaffold attachment factor B (SAF-B) is a nuclear matrix-associated protein. It is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region DNA (MAR) and RNA as a component of hnRNPs.", "TheSAF-A protein is localized to the nuclear matrix", "SAF-A/hnRNP U is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region DNA (MAR) and RNA as a component of hnRNPs. ", "The SAF-A protein localizes to the nucleus where it promotes ribosome biogenesis", "SAF-A is localized to the nucleus where it promotes ribosomal RNA (rRNA) transcription thereby stimulating cell growth." ], "exact_answer": [ "the nucleus" ], "type": "factoid", "id": "5d35e7ddb3a638076300000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "SAF-A/hnRNP U is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region DNA (MAR) and RNA as a component of hnRNPs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19556781", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 212, "text": "Scaffold attachment factor A (SAF-A) participates in the regulation of gene expression by organizing chromatin into transcriptionally active domains and by interacting directly with RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22162999", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1074, "text": "Functional analyses reveal that dual depletion of SAF-A and BRG1 abolishes global transcription by RNA polymerase II, while the nucleolar RNA polymerase I transcription machinery remains unaffected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22162999", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 916, "text": "Using this domain as a probe, we performed a yeast two-hybrid screening and we found that scaffold attachment factor B (SAF-B), a nuclear matrix-associated protein, exhibits protein-protein interaction to this region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10933876", "endSection": "abstract" } ] }, { "body": "Describe Twiddler Syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26652885", "http://www.ncbi.nlm.nih.gov/pubmed/30805057", "http://www.ncbi.nlm.nih.gov/pubmed/19436950", "http://www.ncbi.nlm.nih.gov/pubmed/27354874", "http://www.ncbi.nlm.nih.gov/pubmed/1079649", "http://www.ncbi.nlm.nih.gov/pubmed/29964390", "http://www.ncbi.nlm.nih.gov/pubmed/29759631", "http://www.ncbi.nlm.nih.gov/pubmed/23832019", "http://www.ncbi.nlm.nih.gov/pubmed/28352427", "http://www.ncbi.nlm.nih.gov/pubmed/24407542", "http://www.ncbi.nlm.nih.gov/pubmed/19693314", "http://www.ncbi.nlm.nih.gov/pubmed/18791330", "http://www.ncbi.nlm.nih.gov/pubmed/23181182", "http://www.ncbi.nlm.nih.gov/pubmed/23582129" ], "ideal_answer": [ "Twiddler syndrome is described as a spontaneous rotation or intentional external manipulation of implanted cardiac or occasionally deep brain stimulation (DBS) devices." ], "type": "summary", "id": "5e4606c03f54159529000004", "snippets": [ { "offsetInBeginSection": 171, "offsetInEndSection": 324, "text": "BACKGROUND: Twiddler's, reel, and ratchet syndromes are rare entities responsible for lead displacement of cardiac implantable electronic devices (CIED).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29759631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The twiddler syndrome results in retraction and coiling of the lead in the pacemaker pocket with subsequent pacemaker malfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27354874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Twiddler syndrome is described as a spontaneous rotation or intentional external manipulation of implanted cardiac or occasionally deep brain stimulation (DBS) devices. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26652885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Twiddler's syndrome is a rare cause of pacemaker electrode displacement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Twiddler syndrome is uncommon in children and most commonly described as causing lead retraction with implanted cardiac pacemakers and defibrillators. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23832019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Twiddler syndrome is a form of pacemaker lead dislocation caused by the coiling of the pacemaker leads due to pulse generator rotation on its long axis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24407542", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 676, "text": "On chest X-ray coiling of both atrial and ventricular leads was noted and caused inadvertently by active shoulder-arm physiotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28352427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Twiddler's syndrome, a rare but potentially lethal complication of cardiac pacemaker treatment, is generally diagnosed within the first year of implantation. It is characterized by device malfunction due to dislodgement of cardiac leads resulting from some form of manipulation by the patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23181182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Twiddler syndrome is described as a spontaneous rotation or intentional external manipulation of implanted cardiac or occasionally deep brain stimulation (DBS) devices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26652885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Twiddler syndrome with a twist: a cause of vagal nerve stimulator lead fracture.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23832019", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Twiddler syndrome occurs when a patient intentionally or unintentionally manipulates an implantable generator (usually a pacemaker) and dislodges the pacing leads, causing malfunction of the device.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19436950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "[Total electrode retraction (Twiddler syndrome) in infection of the pacemaker system].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1079649", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Twiddler syndrome is an uncommon complication that occurs by twisting of the generator and may cause torsion , dislodgement , and injury of the leads . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30805057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Twiddler syndrome is a form of pacemaker lead dislocation caused by the coiling of the pacemaker leads due to pulse generator rotation on its long axis . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24407542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Twiddler syndrome is an exceptional cause of dysfunction of cardiac prostheses resulting from a displacement of the probe either by deliberate or unconscious manipulation . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29964390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Twiddler syndrome is described as a spontaneous rotation or intentional external manipulation of implanted cardiac or occasionally deep brain stimulation (DBS) devices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26652885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Twiddler syndrome occurs when a patient intentionally or unintentionally manipulates an implantable generator (usually a pacemaker) and dislodges the pacing leads, causing malfunction of the device.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19436950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Twiddler syndrome is an uncommon complication that occurs by twisting of the generator and may cause torsion, dislodgement, and injury of the leads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30805057", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Twiddler syndrome is a form of pacemaker lead dislocation caused by the coiling of the pacemaker leads due to pulse generator rotation on its long axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24407542", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 269, "text": "Twiddler syndrome is characterized by intentional or inadvertent manipulation of implanted devices in the pacemaker pocket.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19693314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Twiddler's syndrome describes the intentional external manipulation or spontaneous rotation of implanted devices such as cardiac pacemakers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18791330", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 467, "text": "The findings of Twiddler syndrome illustrated here apply to all implanted devices and show the complication of lead fracture in addition to the more commonly reported complication of lead retraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23832019", "endSection": "abstract" } ] }, { "body": "What are Drosophila's balancer chromosomes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28581074", "http://www.ncbi.nlm.nih.gov/pubmed/10431243", "http://www.ncbi.nlm.nih.gov/pubmed/26903656", "http://www.ncbi.nlm.nih.gov/pubmed/3146524" ], "ideal_answer": [ "genetic reagents", "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens.", "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. This problem is of particular importance when the mutant allele has been maintained with a balancer chromosome. From four isogenic lines of Drosophila melanogaster, four sets of recombinant extracted lines were constructed using standard balancer-chromosome techniques", "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. This problem is of particular importance when the mutant allele has been maintained with a balancer chromosome.", "balancer chromosomes are genetic reagents used for stock maintenance and mutagenesis screens" ], "type": "summary", "id": "5d35e114b3a638076300000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10431243", "endSection": "abstract" }, { "offsetInBeginSection": 1402, "offsetInEndSection": 1513, "text": "This problem is of particular importance when the mutant allele has been maintained with a balancer chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3146524", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 652, "text": "From four isogenic lines of Drosophila melanogaster, four sets of recombinant extracted lines were constructed using standard balancer-chromosome techniques", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28581074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Multiply inverted balancer chromosomes that suppress exchange with their homologs are an essential part of the Drosophila melanogaster genetic toolkit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26903656", "endSection": "abstract" }, { "offsetInBeginSection": 1503, "offsetInEndSection": 1748, "text": "Our results reject a simple nonrecombining, clonal mode for the laboratory evolution of balancer chromosomes and have implications for how balancer chromosomes should be used in the design and interpretation of genetic experiments in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26903656", "endSection": "abstract" } ] }, { "body": "What is iodine thyroid blocking?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23475155", "http://www.ncbi.nlm.nih.gov/pubmed/22021061", "http://www.ncbi.nlm.nih.gov/pubmed/27574319", "http://www.ncbi.nlm.nih.gov/pubmed/27664997" ], "ideal_answer": [ "High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later." ], "exact_answer": [ "High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later." ], "type": "factoid", "id": "5e5cc1fa1af46fc130000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "(131)I, when released in a radiological or nuclear accident as happened recently in Fukushima, Japan, may cause thyroid cancer as a long-term consequence. Iodine thyroid blocking (ITB) is known to reduce the risk of developing thyroid cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22021061", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 321, "text": "High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Potassium iodide (KI) to block the thyroid from exposure to I-131", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23475155", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 361, "text": "This article describes the process and methods of developing the revised, evidence-based WHO guidelines for ITB following nuclear and radiological accidents", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27664997", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The First Meeting of the WHO Guideline Development Group for the Revision of the WHO 1999 Guidelines for Iodine Thyroid Blocking.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27664997", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Thyroid Blocking Policy in Hungary and Clarification of Terminology in the Light of Recommendations by International Organisations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27574319", "endSection": "title" } ] }, { "body": "Does gavestinel improve outcomes of stroke patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15831831", "http://www.ncbi.nlm.nih.gov/pubmed/10859040", "http://www.ncbi.nlm.nih.gov/pubmed/11277826", "http://www.ncbi.nlm.nih.gov/pubmed/15243144", "http://www.ncbi.nlm.nih.gov/pubmed/15032709", "http://www.ncbi.nlm.nih.gov/pubmed/11727452", "http://www.ncbi.nlm.nih.gov/pubmed/16340185" ], "ideal_answer": [ "No. In a randomized clinical trial, treatment with gavestinel within 6 hours of acute ischaemic stroke did not improve outcome." ], "exact_answer": "no", "type": "yesno", "id": "5e44c18648dab47f2600001f", "snippets": [ { "offsetInBeginSection": 1332, "offsetInEndSection": 1463, "text": "CONCLUSION: Consistent with the clinical outcomes in the GAIN trials, no effects of gavestinel on ischemic infarction was observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16340185", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1149, "text": "No effects of gavestinel on infarct volume were observed in the primary or other analyses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16340185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831831", "endSection": "title" }, { "offsetInBeginSection": 323, "offsetInEndSection": 396, "text": "Both trials reported that gavestinel was ineffective in ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831831", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1493, "text": "CONCLUSIONS: These observations from the combined GAIN International and GAIN Americas trials suggest that gavestinel is not of substantial benefit or harm to patients with primary intracerebral hemorrhage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831831", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 413, "text": "Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show neuroprotective efficacy in human clinical trials or produced intolerable central nervous system adverse effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15032709", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 934, "text": "METHODS: We studied all patients of the Glycine Antagonist (gavestinel) In Neuroprotection (GAIN) International Trial with ischemic stroke alive at day 7, excluding patients with hemorrhagic events and deaths from nonstroke-related causes. The GAIN International Trial was a randomized, double-blind, placebo-controlled, and parallel-group trial; because the study drug had no effect on stroke outcome, treatment groups were combined for this analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15243144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Gavestinel produces no benefit for stroke patients, study finds.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11727452", "endSection": "title" }, { "offsetInBeginSection": 40, "offsetInEndSection": 287, "text": "The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11727452", "endSection": "abstract" }, { "offsetInBeginSection": 1753, "offsetInEndSection": 1856, "text": "INTERPRETATION: Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10859040", "endSection": "abstract" }, { "offsetInBeginSection": 1759, "offsetInEndSection": 1862, "text": "INTERPRETATION\n\nTreatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10859040", "endSection": "abstract" }, { "offsetInBeginSection": 2271, "offsetInEndSection": 2414, "text": "CONCLUSION\n\nIn this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11277826", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 394, "text": "Both trials reported that gavestinel was ineffective in ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831831", "endSection": "abstract" }, { "offsetInBeginSection": 1753, "offsetInEndSection": 1855, "text": "INTERPRETATION Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10859040", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 395, "text": "Both trials reported that gavestinel was ineffective in ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15831831", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Gavestinel produces no benefit for stroke patients , study finds .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11727452", "endSection": "title" }, { "offsetInBeginSection": 40, "offsetInEndSection": 287, "text": "The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11727452", "endSection": "abstract" }, { "offsetInBeginSection": 40, "offsetInEndSection": 286, "text": "The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11727452", "endSection": "abstract" }, { "offsetInBeginSection": 1725, "offsetInEndSection": 1812, "text": "Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10859040", "endSection": "abstract" }, { "offsetInBeginSection": 2171, "offsetInEndSection": 2302, "text": "In this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11277826", "endSection": "abstract" } ] }, { "body": "Can Systemic Lupus Erythematosus cause seizures?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18813701", "http://www.ncbi.nlm.nih.gov/pubmed/15985581", "http://www.ncbi.nlm.nih.gov/pubmed/22492779", "http://www.ncbi.nlm.nih.gov/pubmed/28387089", "http://www.ncbi.nlm.nih.gov/pubmed/15557494", "http://www.ncbi.nlm.nih.gov/pubmed/17875548", "http://www.ncbi.nlm.nih.gov/pubmed/29208845", "http://www.ncbi.nlm.nih.gov/pubmed/29103182" ], "ideal_answer": [ "In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE)", "Yes, Systemic Lupus Erythematosus s an autosomal recessive disorder can cause seizures.", "Yes, Seizure can be caused by Systemic Lupus Erythematosus." ], "exact_answer": "yes", "type": "yesno", "id": "5e4c06d96d0a27794100002e", "snippets": [ { "offsetInBeginSection": 627, "offsetInEndSection": 852, "text": "The mean \u00b1 SD age at SLE diagnosis and at onset of PRES was 25.02 \u00b1 13.78 and 28.31 \u00b1 12.61\u00a0years, respectively. Seizure was the most common presenting symptom, as seen in 28 episodes, followed by acute severe headache in 17,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29103182", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 254, "text": "Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29208845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Seizures are one of the most serious neuropsychiatric manifestations of systemic lupus erythematous (SLE). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28387089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The aim of this study was to describe the frequency , attribution , outcome and predictors of seizures in systemic lupus erythematosus ( SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "OBJECTIVE\nTo evaluate the frequency and risk factors of epileptic seizures in a large cohort of patients with systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15557494", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 586, "text": "Epileptic seizures occurred at the onset of SLE symptoms in 19 (31.6%) and after the onset of SLE in 41 of 60 (68.3%) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15557494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Epileptic seizures and EEG features in juvenile systemic lupus erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18813701", "endSection": "title" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1266, "text": "CONCLUSIONS\nEpileptic seizures were observed in 11.2% of systemic lupus erythematosus (SLE) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15557494", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1533, "text": "CONCLUSIONS\nSeizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17875548", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1488, "text": "Seizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17875548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "To determine the factors associated with seizures in systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15985581", "endSection": "abstract" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1527, "text": "Neurologic manifestations, in special epileptic seizures, are frequent in systemic lupus erythematosus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18813701", "endSection": "abstract" } ] }, { "body": "What disease is associated with a Malar rash?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7607795", "http://www.ncbi.nlm.nih.gov/pubmed/31619142", "http://www.ncbi.nlm.nih.gov/pubmed/27498665", "http://www.ncbi.nlm.nih.gov/pubmed/891079", "http://www.ncbi.nlm.nih.gov/pubmed/1824645" ], "ideal_answer": [ "Cutaneous manifestations of SLE are frequently the presenting symptoms, typically noted in the classic malar \"butterfly\" rash;", "Malar rash is associated with a disease of the skin called Systemic lupus erythematosis.", "Malar rash is a systemic lupus erythematosus (SLE) syndrome characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and chronic course.", "The malar or butterfly rash is seen on the face and is associated with systemic Lupus erythematosus", " Cutaneous manifestations of SLE are frequently the presenting symptoms, typically noted in the classic malar \"butterfly\" rash;", "the cutaneous effects of sle are frequently the presenting symptoms. typically noted in the classic malar \"butterfly \" rash", "Malar rash is associated with a Systemic lupus erythematosus.", " Cutaneous manifestations of SLE are frequently the presenting symptoms, typically noted in the classic malar \"butterfly\" rash; " ], "exact_answer": [ "butterfly rash associated with SLE" ], "type": "factoid", "id": "5e4bed1c6d0a27794100002b", "snippets": [ { "offsetInBeginSection": 306, "offsetInEndSection": 434, "text": " Cutaneous manifestations of SLE are frequently the presenting symptoms, typically noted in the classic malar \"butterfly\" rash; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7607795", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Malar rash is one of the three cutaneous diagnostic criteria of systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31619142", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of rogaratinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31405822", "http://www.ncbi.nlm.nih.gov/pubmed/29451369", "http://www.ncbi.nlm.nih.gov/pubmed/30807645" ], "ideal_answer": [ "Rogaratinib is a highly potent and selective small-molecule pan-fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application currently being investigated in phase 1 clinical trials for the treatment of cancer." ], "type": "summary", "id": "5e44bc4c48dab47f2600001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Rogaratinib (BAY 1163877) is a highly potent and selective small-molecule pan-fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application currently being investigated in phase\u20051 clinical trials for the treatment of cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Discovery of Rogaratinib (BAY 1163877): a pan-FGFR Inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451369", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 278, "text": "In preclinical studies, high tumour FGFR mRNA expression predicted response to rogaratinib, an oral pan-FGFR inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31405822", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 277, "text": "In preclinical studies, high tumour FGFR mRNA expression predicted response to rogaratinib, an oral pan-FGFR inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31405822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Rogaratinib (BAY 1163877) is a highly potent and selective small-molecule pan-fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application currently being investigated in phase\u20051 clinical trials for the treatment of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30807645", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Rogaratinib ( BAY 1163877 ) is a highly potent and selective small-molecule pan-fibroblast growth factor receptor ( FGFR ) inhibitor ( FGFR1-4 ) for oral application currently being investigated in phase 1 clinical trials for the treatment of cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Discovery of Rogaratinib ( BAY 1163877): a pan-FGFR Inhibitor", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29451369", "endSection": "title" }, { "offsetInBeginSection": 158, "offsetInEndSection": 278, "text": "In preclinical studies, high tumour FGFR mRNA expression predicted response to rogaratinib, an oral pan-FGFR inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31405822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30807645", "endSection": "title" }, { "offsetInBeginSection": 503, "offsetInEndSection": 635, "text": "In vitro kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3 and 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30807645", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 503, "text": "Here, we evaluated the activity of a novel pan-FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30807645", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 502, "text": "Here, we evaluated the activity of a novel pan-FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30807645", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 634, "text": "In vitro kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3 and 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30807645", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 266, "text": "In preclinical studies, high tumour FGFR mRNA expression predicted response to rogaratinib, an oral pan-FGFR inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31405822", "endSection": "abstract" } ] }, { "body": "Which epigenetic mark is deposited by PRC2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27410265", "http://www.ncbi.nlm.nih.gov/pubmed/27216774", "http://www.ncbi.nlm.nih.gov/pubmed/22158708", "http://www.ncbi.nlm.nih.gov/pubmed/28256832", "http://www.ncbi.nlm.nih.gov/pubmed/17525233", "http://www.ncbi.nlm.nih.gov/pubmed/24469045", "http://www.ncbi.nlm.nih.gov/pubmed/18931660", "http://www.ncbi.nlm.nih.gov/pubmed/19377285", "http://www.ncbi.nlm.nih.gov/pubmed/23326524" ], "ideal_answer": [ "H3K27me3 is the major histone methyltransferase activity of PRC2.", "The Polycomb Repressive Complex 2 (PRC2) has been identified as a key regulator of epigenetic mark H3K27me3.", "There are data showing coordinate regulation between DNAme and H3K27me3, which are both involved in the establishment and maintenance of epigenetic gene silencing. We found that the Polycomb Repressive Complex 2 (PRC2), which is responsible for di- and trimethylation of H3K27 (H3K27me2/me3), binds to its own site of methylation.", "H3K27me3 is the endogenous epigenetic mark deposited by PRC2.", "H3K27me3 is an epigenetic mark deposited by PRC2 (Polycomb repressive complex 2).", "polycomb repressive complex 2 (prc2 ) mediates trimethylation of lysine 27 on histone h3", "Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, which establishes H3K27me3 repressive epigenetic marks that promote tissue-specific differentiation by silencing ectopic gene programs.", "PRC2 is H3K27me3 ubiquitously-associated and acts as an epigenetic mark deposition mechanism." ], "exact_answer": [ "H3K27me3" ], "type": "factoid", "id": "5d35ef017bc3fee31f000001", "snippets": [ { "offsetInBeginSection": 126, "offsetInEndSection": 229, "text": "polycomb repressive complex 2 (PRC2), which mediates trimethylation of lysine 27 on histone H3 (K27me3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525233", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 317, "text": "PRC2, has an additional function to stimulate the PRC2 activity after binding to H3K27me3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28256832", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 569, "text": "In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27410265", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1209, "text": "Knockdown of PRC2 H3K27-methyltransferases Ezh2 and Ezh1, or forced expression of the Trithorax/COMPASS subunit Wdr5 activates Runx2/p57 mRNA expression in both immature and mature hippocampal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27216774", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 507, "text": "Here, we show that, in cancer cells, the epigenetic remodeling of chromatin into hypoacetylated domains covered with histone H3K27 trimethylation is paralleled by changes in higher-order chromatin structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24469045", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 477, "text": " There are data showing coordinate regulation between DNAme and H3K27me3, which are both involved in the establishment and maintenance of epigenetic gene silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326524", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 328, "text": "Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, which establishes H3K27me3 repressive epigenetic marks that promote tissue-specific differentiation by silencing ectopic gene programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22158708", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 909, "text": "We found that the Polycomb Repressive Complex 2 (PRC2), which is responsible for di- and trimethylation of H3K27 (H3K27me2/me3), binds to its own site of methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19377285", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 500, "text": "Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18931660", "endSection": "abstract" } ] }, { "body": "Is Impetigo a viral infection that affects the skin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28178083", "http://www.ncbi.nlm.nih.gov/pubmed/15482208", "http://www.ncbi.nlm.nih.gov/pubmed/29745242", "http://www.ncbi.nlm.nih.gov/pubmed/26280141", "http://www.ncbi.nlm.nih.gov/pubmed/29898217", "http://www.ncbi.nlm.nih.gov/pubmed/26336623", "http://www.ncbi.nlm.nih.gov/pubmed/25250996", "http://www.ncbi.nlm.nih.gov/pubmed/16218885", "http://www.ncbi.nlm.nih.gov/pubmed/7899177", "http://www.ncbi.nlm.nih.gov/pubmed/28196318", "http://www.ncbi.nlm.nih.gov/pubmed/29063621", "http://www.ncbi.nlm.nih.gov/pubmed/17367045", "http://www.ncbi.nlm.nih.gov/pubmed/29416987" ], "ideal_answer": [ "No, impetigo is a highly contagious bacterial skin infection" ], "exact_answer": "no", "type": "yesno", "id": "5e4fd4d56d0a277941000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Importance: Ozenoxacin, a novel topical antibacterial agent with potent bactericidal activity against gram-positive bacteria, has been developed as a cream with 1% active drug for the treatment of impetigo, a highly contagious bacterial skin infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29898217", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 185, "text": ": To compare the in vitro activity of the anti-impetigo agent, ozenoxacin, and other antimicrobial agents against Gram-positive clinical isolates from skin and soft tissue infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29745242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29416987", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 143, "text": "Impetigo is a highly contagious bacterial skin infection and is one of the most common skin infections in children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29063621", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1020, "text": "Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280141", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 179, "text": "Impetigo is the most common bacterial skin infection of children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7899177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Impetigo is the most common bacterial skin infection in children two to five years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25250996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "BACKGROUND Impetigo can result from Staphylococcus aureus (S. aureus).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26336623", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 720, "text": "Impetigo , cellulitis , and abscess comprise the majority of childhood bacterial skin infections and are treated with topical or systemic antibiotics that cover group A Streptococcus and Staphylococcus aureus . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28196318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "BACKGROUND\nImpetigo can result from Staphylococcus aureus (S. aureus).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26336623", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1021, "text": "Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26280141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Impetigo is a superficial, but contagious, bacterial infection of the skin that predominantly affects children and is common in primary care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17367045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Impetigo is a common, superficial, bacterial infection of the skin characterized by an inflamed and infected epidermis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15482208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Impetigo, a bacterial skin infection that involves the superficial layers of the skin, is one of the most common skin infections in children ages 2 to 5 but can occur in individuals across the lifespan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28178083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Impetigo contagiosa is a common, superficial, bacterial infection of the skin characterised by an inflamed and infected epidermis caused by Staphylococcus aureus, Streptococcus pyogenes or both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16218885", "endSection": "abstract" } ] }, { "body": "List diseases that are caused by the Meningococcus B?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12642606", "http://www.ncbi.nlm.nih.gov/pubmed/16825336", "http://www.ncbi.nlm.nih.gov/pubmed/28778616" ], "ideal_answer": [ "The prevention of paediatric bacterial meningitis and septicaemia has recently entered a new era with the availability of two vaccines against capsular group B meningococcus", "Both bacterial meningitis and septicemia can be caused by Meningococcus B", "the prevention of paediatric bacterial meningitis and septicaemia has entered a new era with the availability of two vaccines against capsular group b meningoco" ], "exact_answer": [ [ "meningitis" ], [ "septicemia" ] ], "type": "list", "id": "5e4027f948dab47f2600000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The prevention of paediatric bacterial meningitis and septicaemia has recently entered a new era with the availability of two vaccines against capsular group B meningococcus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28778616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16825336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Sepsis and meningitis caused by serogroup B meningococcus are devastating diseases of infants and young adults , which cannot yet be prevented by vaccination . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12642606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The prevention of paediatric bacterial meningitis and septicaemia has recently entered a new era with the availability of two vaccines against capsular group B meningococcus ( MenB) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28778616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16825336", "endSection": "abstract" } ] }, { "body": "Should Lubeluzole be used for treatment of ischemic stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29550817", "http://www.ncbi.nlm.nih.gov/pubmed/28939972", "http://www.ncbi.nlm.nih.gov/pubmed/8553408", "http://www.ncbi.nlm.nih.gov/pubmed/11869612", "http://www.ncbi.nlm.nih.gov/pubmed/11062273", "http://www.ncbi.nlm.nih.gov/pubmed/12038658", "http://www.ncbi.nlm.nih.gov/pubmed/9412611", "http://www.ncbi.nlm.nih.gov/pubmed/9619701" ], "ideal_answer": [ "No. Lubeluzole failed to consistently show an efficacy in the treatment of acute stroke and should not be used." ], "exact_answer": "no", "type": "yesno", "id": "5e44caaf48dab47f26000024", "snippets": [ { "offsetInBeginSection": 729, "offsetInEndSection": 870, "text": "Lubeluzole showed promising neuroprotective effects in animal stroke models, but failed to show benefits in acute ischemic stroke in humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28939972", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 311, "text": "However, clinical research on lubeluzole is now at a standstill, since lubeluzole seems to be associated with the acquired long QT syndrome and ventricular arrhythmias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29550817", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 696, "text": "Ten classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12038658", "endSection": "abstract" }, { "offsetInBeginSection": 2385, "offsetInEndSection": 2484, "text": "CONCLUSIONS: This study failed to show an efficacy of lubeluzole in the treatment of acute stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11062273", "endSection": "abstract" }, { "offsetInBeginSection": 1816, "offsetInEndSection": 2125, "text": "Overall, of all treated patients, 401 (22.5%) died: 203 (22.5%) in the lubeluzole group and 198 (22.4%) with placebo. Of all subjects treated, 853 (95%) on lubeluzole and 826 (93%) on placebo reported an adverse event during their treatment period or within the next 2 days after discontinuation of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11062273", "endSection": "abstract" }, { "offsetInBeginSection": 1760, "offsetInEndSection": 1976, "text": "CONCLUSIONS: Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611", "endSection": "abstract" }, { "offsetInBeginSection": 1088, "offsetInEndSection": 1700, "text": "RESULTS: The overall mortality rate at 12 weeks for lubeluzole-treated patients was 20.7% compared to 25.2% for placebo-treated patients (NS). Controlling for relevant covariates, the degree of neurological recovery (NIHSS) at week 12 significantly favored lubeluzole over placebo (P = .033). Lubeluzole treatment similarly resulted in significantly greater improvements in functional status (Barthel Index) (P = .038) and overall disability (Rankin Scale) (P = .034) after 12 weeks. A global test statistic confirmed that lubeluzole-treated patients had a more favorable clinical outcome at 12 weeks (P = .041).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611", "endSection": "abstract" }, { "offsetInBeginSection": 1922, "offsetInEndSection": 2121, "text": "CONCLUSIONS: In patients with acute ischemic stroke, the dosage regimen of 7.5 mg over 1 hour followed by 10 mg/d of intravenous lubeluzole is safe and statistically significantly reduced mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8553408", "endSection": "abstract" }, { "offsetInBeginSection": 1766, "offsetInEndSection": 1982, "text": "CONCLUSIONS\n\nTreatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611", "endSection": "abstract" }, { "offsetInBeginSection": 2301, "offsetInEndSection": 2594, "text": "CONCLUSIONS: Lubeluzole, given in the acute phase of ischaemic stroke, is not associated with a significant reduction of death or dependency at the end of scheduled follow-up period but seems to be associated with a significant increase of heart-conduction disorders (Q-T prolonged >450 msec).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11869612", "endSection": "abstract" }, { "offsetInBeginSection": 1721, "offsetInEndSection": 1924, "text": "Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9412611", "endSection": "abstract" }, { "offsetInBeginSection": 1963, "offsetInEndSection": 2123, "text": "In the overall study population, treatment with intravenous lubeluzole within 6 h of the onset of ischaemic stroke did not affect mortality or clinical outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9619701", "endSection": "abstract" } ] }, { "body": "What is vivotif?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28515625" ], "ideal_answer": [ "Vivotif(r) is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe. It is indicated for adults and children from 5 years of age upwards. Specifically, in the most developed countries, vaccination is suggested for highrisk population groups and particularly for international travellers to destinations where the risk of contracting typhoid fever is high. Vivotif(r) appears to be a powerful means of disease prevention, the importance of which is highlighted by the spread of antibiotic-resistant strains of Salmonella typhy (S. typhi)." ], "type": "summary", "id": "5e76384fc6a8763d2300000e", "snippets": [ { "offsetInBeginSection": 57, "offsetInEndSection": 93, "text": "Utility of Ty21a vaccine (Vivotif\u00ae).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28515625", "endSection": "title" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1348, "text": "Vivotif\u00ae is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe. It is indicated for adults and children from 5 years of age upwards. Specifically, in the most developed countries, vaccination is suggested for highrisk population groups and particularly for international travellers to destinations where the risk of contracting typhoid fever is high. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28515625", "endSection": "abstract" }, { "offsetInBeginSection": 1584, "offsetInEndSection": 1763, "text": "Vivotif\u00ae appears to be a powerful means of disease prevention, the importance of which is highlighted by the spread of antibiotic-resistant strains of Salmonella typhy (S. typhi).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28515625", "endSection": "abstract" } ] }, { "body": "List types of cancer where TBC1 domain family member 16 (TBC1D16) is involved", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29962380", "http://www.ncbi.nlm.nih.gov/pubmed/31383000", "http://www.ncbi.nlm.nih.gov/pubmed/26030178" ], "ideal_answer": [ "TBC1D16 is a predictive marker for favorable prognosis of Epithelial ovarian cancer (EOC). In addition, a short isoform of TBC1D16 (TBC1D16-47KD) exacerbates melanoma growth and metastasis both in vitro and in vivo.", "TBC1 domain family member 16 (Tbc1D16) is involved in several types of cancer. These include epithelial ovarian cancer, gastric cancer, breast cancer, cervical cancer, adenocarcinoma, colorectal cancer, Hodgkin lymphoma, nasopharyngeal carcinoma and oral squamous cell carcinoma." ], "exact_answer": [ [ "Epithelial ovarian cancer (EOC)" ], [ "Melanoma" ] ], "type": "list", "id": "5e52c1fd6d0a27794100004c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Expression of TBC1D16 Is Associated with Favorable Prognosis of Epithelial Ovarian Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29962380", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1648, "text": "Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy with high recurrence and poor prognosis duo to the lack of effective biomarkers. TBC1 domain family member 16 (TBC1D16), a GTPase-activating protein, is involved in regulating intracellular trafficking in tumorigenesis and metastasis. However, the clinical significance of TBC1D16 in EOC remains unknown. In the present study, we investigated the expression and prognostic significance of TBC1D16 in EOC and its relationship with the expression of vascular endothelial growth factor (VEGF). The tissue specimens included 156 histologically confirmed EOC and 30 normal ovarian tissues. The expression of TBC1D16 and VEGF was detected by immunohistochemistry (IHC), and the immunoreactive score was calculated with signal intensity and percentage of positive cells. IHC results showed that TBC1D16 and VEGF were both mainly localized in cytoplasm of epithelial cells in normal ovarian tissues and were expressed in cancer cells. Based on the immunoreactive score, TBC1D16 expression in EOC was categorized as \"high expression,\" compared with normal ovarian tissues (P < 0.05). The Chi-square test showed that high TBC1D16 expression was related to advanced pT stages (P = 0.029), but not correlated with other clinical features. Moreover, the TBC1D16 expression was significantly higher in EOC specimens with low VEGF expression (P < 0.001). Importantly, in both univariate and multivariate survival analyses, high expression of TBC1D16 was significantly correlated with good overall survival (OS). In conclusion, TBC1D16 is a predictive marker for favorable prognosis of EOC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29962380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26030178", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 994, "text": "Metastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26030178", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 1000, "text": "IHC results showed that TBC1D16 and VEGF were both mainly localized in cytoplasm of epithelial cells in normal ovarian tissues and were expressed in cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29962380", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1148, "text": "Based on the immunoreactive score, TBC1D16 expression in EOC was categorized as \"high expression,\" compared with normal ovarian tissues (P < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29962380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Expression of TBC1D16 Is Associated with Favorable Prognosis of Epithelial Ovarian Cancer .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29962380", "endSection": "title" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1172, "text": "Based on the immunoreactive score , TBC1D16 expression in EOC was categorized as \" high expression , \" compared with normal ovarian tissues ( P < 0.05) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29962380", "endSection": "abstract" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1063, "text": "In addition, hypomethylation of TBC1D16 was observed in multiple tumours, including a breast cancer primary/metastasis pair, and to a lesser degree in melanoma, although again not all tumours or cancer primary/metastasis pairs exhibited altered patterns of methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND\nCharacteristic DNA methylation differences have been identified between primary and metastatic melanomas at EBF3 and/or TBC1D16 gene loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383000", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 994, "text": "We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26030178", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1061, "text": "In addition, hypomethylation of TBC1D16 was observed in multiple tumours, including a breast cancer primary/metastasis pair, and to a lesser degree in melanoma, although again not all tumours or cancer primary/metastasis pairs exhibited altered patterns of methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383000", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 1041, "text": "In addition, hypomethylation of TBC1D16 was observed in multiple tumours, including a breast cancer primary/metastasis pair, and to a lesser degree in melanoma, although again not all tumours or cancer primary/metastasis pairs exhibited altered patterns of methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383000", "endSection": "abstract" } ] }, { "body": "What does osanetant and talnetant have in common?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25107588", "http://www.ncbi.nlm.nih.gov/pubmed/21417773" ], "ideal_answer": [ "Osanetant and talnetant are selective NK3 antagonists. Preclinical and Phase II clinical results of osanetant and talnetant in schizophrenic patients have indicated that NK(3) antagonists may provide significant improvement of the positive symptoms and cognitive impairment associated with this disorder." ], "type": "summary", "id": "5e550b5db761aafe09000007", "snippets": [ { "offsetInBeginSection": 140, "offsetInEndSection": 307, "text": "Phase II clinical trials in schizophrenia with two selective NK3 antagonists (osanetant and talnetant) have demonstrated significant improvement in positive symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25107588", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 419, "text": "Preclinical and Phase II clinical results of osanetant and talnetant in schizophrenic patients have indicated that NK(3) antagonists may provide significant improvement of the positive symptoms and cognitive impairment associated with this disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21417773", "endSection": "abstract" } ] }, { "body": "List SLC25A46-related pathologies", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28376086" ], "ideal_answer": [ "The mitochondrial protein SLC25A46 has been recently identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital pontocerebellar hypoplasia.", "The mitochondrial protein SLC25A46 has been identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia, lethal congenital pontocerebellar hypoplasia and lethal neuropathology", "SLC25A46-related pathologies include Charcot-Marie-Tooth disease type 2, Leigh syndrome, progressive myoclonic ataxia, lethal congenital pontocerebellar hypoplasia, autosomal dominant optic atrophy, Menkes disease, hyper-IgM with immunodeficiency syndrome (HIGM), and anterior pituitary aplasia.", "SLC25A46-related pathologies include optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital ptacerebellar hypoplasia." ], "exact_answer": [ [ "inherited optic atrophy" ], [ "Charcot-Marie-Tooth type 2" ], [ "Leigh syndrome" ], [ "Progressive myoclonic ataxia" ], [ "Lethal congenital pontocerebellar hypoplasia" ], [ "Lethal neuropathology" ] ], "type": "list", "id": "5e36e254b5b409ea53000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "The mitochondrial protein SLC25A46 has been recently identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital pontocerebellar hypoplasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28376086", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 1227, "text": "Here we identified a loss-of-function mutation in the Slc25a46 gene that causes lethal neuropathology in mice. Mutant mice manifest the main clinical features identified in patients, including ataxia, optic atrophy and cerebellar hypoplasia, which were completely rescued by expression of the human ortholog. Histopathological analysis revealed previously unseen lesions, most notably disrupted cytoarchitecture in the cerebellum and retina and prominent abnormalities in the neuromuscular junction. A distinct lymphoid phenotype was also evident. Our mutant mice provide a valid model for understanding the mechanistic basis of the complex SLC25A46-mediated pathologies, as well as for screening potential therapeutic interventions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28376086", "endSection": "abstract" } ] }, { "body": "What is the target of galcanezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30341990", "http://www.ncbi.nlm.nih.gov/pubmed/30187471", "http://www.ncbi.nlm.nih.gov/pubmed/31710104", "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "http://www.ncbi.nlm.nih.gov/pubmed/29310444", "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "http://www.ncbi.nlm.nih.gov/pubmed/30378008", "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "http://www.ncbi.nlm.nih.gov/pubmed/31043785", "http://www.ncbi.nlm.nih.gov/pubmed/29089894", "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "http://www.ncbi.nlm.nih.gov/pubmed/31253091", "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "http://www.ncbi.nlm.nih.gov/pubmed/29848108", "http://www.ncbi.nlm.nih.gov/pubmed/31482569", "http://www.ncbi.nlm.nih.gov/pubmed/31291515" ], "ideal_answer": [ "Galcanezumab is a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention." ], "exact_answer": [ "calcitonin gene-related peptide" ], "type": "factoid", "id": "5e460f823f54159529000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Importance: Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Background Safety findings from a Phase 2b study of galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, for prevention of migraine (NCT02163993) are reported here.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310444", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1379, "text": "Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29697153", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 778, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29848108", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 366, "text": "Galcanezumab is an antibody that binds to the ligand calcitonin gene-related peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "title" }, { "offsetInBeginSection": 695, "offsetInEndSection": 905, "text": "Insights regarding the pharmacokinetic/pharmacodynamic properties of galcanezumab as a probe antibody drug and calcitonin gene-related peptide as its binding ligand regarding its clinical outcomes are provided.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 298, "text": "Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31291515", "endSection": "abstract" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1843, "text": "A galcanezumab pharmacokinetic/pharmacodynamic model shows that galcanezumab decreases free calcitonin gene-related peptide concentrations in a dose- and time-dependent manner and continues to suppress free calcitonin gene-related peptide with repeated dosing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 777, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Importance\n\nGalcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 363, "text": "Galcanezumab is an antibody that binds to the ligand calcitonin gene-related peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 283, "text": "The humanized monoclonal antibody galcanezumab (LY2951742) binds to CGRP and may be effective in migraine prophylaxis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29089894", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 408, "text": "Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31253091", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 284, "text": "The humanized monoclonal antibody galcanezumab (LY2951742) binds to CGRP and may be effective in migraine prophylaxis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29089894", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 421, "text": "Failures in development of small molecule CGRP receptor antagonists and increasing knowledge and use of monoclonal antibodies ( mAbs ) in medicine led to the breakthrough development of large molecule anti-CGRP mAbs: eptinezumab , erenumab , fremanezumab , and galcanezumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30187471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab , an anti-CGRP antibody", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Monoclonal antibodies ( mAbs ) targeting the calcitonin-gene-related peptide ( CGRP ) pathway have been developed for episodic and chronic migraine prevention , either through binding the CGRP ligand ( eptinezumab , fremanezumab , galcanezumab ) or the CGRP receptor ( erenumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 298, "text": "Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31291515", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 247, "text": "BACKGROUND: Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide and is indicated for preventive treatment of migraine.DESIGN/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31710104", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 365, "text": "BACKGROUND: Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30341990", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 364, "text": "Galcanezumab is an antibody that binds to the ligand calcitonin gene-related peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 300, "text": "Galcanezumab is one of the antibodies developed and studied to prevent migraine by targeting CGRP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31043785", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Galcanezumab-gnlm (Emgality\u2122; Eli Lilly and Company), hereafter galcanezumab, is a humanized monoclonal antibody against the calcitonin gene-related peptide (CGRP) ligand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30378008", "endSection": "abstract" }, { "offsetInBeginSection": 1579, "offsetInEndSection": 1839, "text": "A galcanezumab pharmacokinetic/pharmacodynamic model shows that galcanezumab decreases free calcitonin gene-related peptide concentrations in a dose- and time-dependent manner and continues to suppress free calcitonin gene-related peptide with repeated dosing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the CGRP Binding Monoclonal Antibody LY2951742 (Galcanezumab) in Healthy Volunteers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29089894", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29255900", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 396, "text": "Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31253091", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 286, "text": "Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31291515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Galcanezumab is a humanized immunoglobulin G (IgG) monoclonal antibody (mAb) indicated for the prevention of migraine that binds to calcitonin gene-related peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31482569", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 346, "text": "Galcanezumab is an antibody that binds to the ligand calcitonin gene-related peptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917684", "endSection": "abstract" } ] }, { "body": "Which disease was studied in the CADISS trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28087823", "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "http://www.ncbi.nlm.nih.gov/pubmed/22855862", "http://www.ncbi.nlm.nih.gov/pubmed/22110554", "http://www.ncbi.nlm.nih.gov/pubmed/19386884", "http://www.ncbi.nlm.nih.gov/pubmed/30801621", "http://www.ncbi.nlm.nih.gov/pubmed/25684164" ], "ideal_answer": [ "CADISS was a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection." ], "exact_answer": [ "carotid and vertebral artery dissection" ], "type": "factoid", "id": "5e4604d83f54159529000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Prognosis of carotid dissecting aneurysms: Results from CADISS and a systematic review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28087823", "endSection": "title" }, { "offsetInBeginSection": 262, "offsetInEndSection": 497, "text": "METHODS: We included 264 patients with extracranial cervical artery dissection (CAD) from the Cervical Artery Dissection in Stroke Study (CADISS), a multicenter prospective study that compared antiplatelet with anticoagulation therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28087823", "endSection": "abstract" }, { "offsetInBeginSection": 1451, "offsetInEndSection": 1602, "text": "CONCLUSIONS: The results of CADISS provide evidence suggesting that DAs may have benign prognosis and therefore medical treatment should be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28087823", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25684164", "endSection": "title" }, { "offsetInBeginSection": 379, "offsetInEndSection": 540, "text": "We compared their efficacy in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional aim of establishing the true risk of recurrent stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25684164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "OBJECTIVE: To present the results of the nonrandomized arm of the Cervical Artery Dissection in Stroke Study (CADISS-NR) trial, comparing anticoagulation and antiplatelets for prevention of recurrent stroke after carotid and vertebral dissection, and perform a meta-analysis of these results with previously published studies comparing the 2 therapeutic strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22855862", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 823, "text": "Although optimal treatment for VAD is unknown, the Cervical Artery Dissection in Stroke Study (CADISS) is an ongoing randomised multicentre prospective study comparing antiplatelet therapy with anticoagulation for patients with both carotid artery dissection and VAD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19386884", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 720, "text": "We use dual antiplatelets for the management of cervical dissections as a part of the CADISS trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22110554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Antiplatelet therapy vs. anticoagulation in cervical artery dissection: rationale and design of the Cervical Artery Dissection in Stroke Study (CADISS).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "title" }, { "offsetInBeginSection": 535, "offsetInEndSection": 679, "text": "AIMS: CADISS is a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 681, "text": "AIMS\n\nCADISS is a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 719, "text": "We use dual antiplatelets for the management of cervical dissections as a part of the CADISS trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22110554", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 678, "text": "AIMS CADISS is a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection: The Cervical Artery Dissection in Stroke Study ( CADISS ) Randomized Clinical Trial Final Results .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30801621", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Antiplatelet therapy vs. anticoagulation in cervical artery dissection: rationale and design of the Cervical Artery Dissection in Stroke Study ( CADISS ) .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "title" }, { "offsetInBeginSection": 369, "offsetInEndSection": 533, "text": "We compared their efficacy in the Cervical Artery Dissection in Stroke Study ( CADISS) , with the additional aim of establishing the true risk of recurrent stroke .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25684164", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 540, "text": "We compared their efficacy in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional aim of establishing the true risk of recurrent stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25684164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "OBJECTIVE\nTo present the results of the nonrandomized arm of the Cervical Artery Dissection in Stroke Study (CADISS-NR) trial, comparing anticoagulation and antiplatelets for prevention of recurrent stroke after carotid and vertebral dissection, and perform a meta-analysis of these results with previously published studies comparing the 2 therapeutic strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22855862", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 720, "text": "We use dual antiplatelets for the management of cervical dissections as a part of the CADISS trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22110554", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 681, "text": "AIMS\nCADISS is a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 152, "text": "anticoagulation in cervical artery dissection: rationale and design of the Cervical Artery Dissection in Stroke Study (CADISS).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection: The Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30801621", "endSection": "title" }, { "offsetInBeginSection": 555, "offsetInEndSection": 822, "text": "Although optimal treatment for VAD is unknown, the Cervical Artery Dissection in Stroke Study (CADISS) is an ongoing randomised multicentre prospective study comparing antiplatelet therapy with anticoagulation for patients with both carotid artery dissection and VAD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19386884", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 663, "text": "CADISS is a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18705933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "To present the results of the nonrandomized arm of the Cervical Artery Dissection in Stroke Study (CADISS-NR) trial, comparing anticoagulation and antiplatelets for prevention of recurrent stroke after carotid and vertebral dissection, and perform a meta-analysis of these results with previously published studies comparing the 2 therapeutic strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22855862", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 528, "text": "We compared their efficacy in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional aim of establishing the true risk of recurrent stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25684164", "endSection": "abstract" } ] }, { "body": "What is the human RCA locus size in bps?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2564419", "http://www.ncbi.nlm.nih.gov/pubmed/2451706", "http://www.ncbi.nlm.nih.gov/pubmed/19319518", "http://www.ncbi.nlm.nih.gov/pubmed/2164822" ], "ideal_answer": [ "The human RCA locus is located on chromosome 1 (CA1) and consists of approximately 750 kb.", "Genome and expressed sequence tag information of Xenopus tropicalis suggested that short-consensus repeat (SCR)-containing proteins are encoded by three genes that are mapped within a 300-kb downstream of PFKFB2, which is a marker gene for the regulator of complement activation (RCA) loci in human and chicken", "The locus containing the ribosomal protein A (RCA) gene is located at a perinuclear structure 3 kb from the left end and 610 kb in bps, leaving a footprint of 7.4 kb on chromosome 1.", "The human RCA locus is located on chromosome 1q21-32 and measures approximately 2-3 kb in bps.", "The human RCA locus is located on chromosome 1q21-32 and consists of approximately 150 tandemly repeated copies of a 9.1 kb locus." ], "exact_answer": [ "300kbp" ], "type": "factoid", "id": "5d35d901b3a638076300000a", "snippets": [ { "offsetInBeginSection": 196, "offsetInEndSection": 400, "text": " The human homologues of these genes are tightly linked, composing the RCA locus, which maps to human chromosome (Chr.)1q32, within a large linkage group conserved between human Chr.1q21-32 and mouse Chr.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2564419", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 402, "text": "The primary sequence of the most common structural allotype of CR1 and that of CR2 have been established, and ligand binding on the molecules has been mapped. CR1 and CR2 genes are located in close vicinity in the RCA locus of chromosome 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2164822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Genome and expressed sequence tag information of Xenopus tropicalis suggested that short-consensus repeat (SCR)-containing proteins are encoded by three genes that are mapped within a 300-kb downstream of PFKFB2, which is a marker gene for the regulator of complement activation (RCA) loci in human and chicken.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19319518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "The organization and physical linkage of four members of a major complement locus, the RCA locus, have been determined using the technique of pulsed field gradient gel electrophoresis in conjunction with Southern blotting", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2451706", "endSection": "abstract" } ] }, { "body": "Is there a role for TET proteins in invariant natural killer T cells (iNKT) cell fate?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27869820" ], "ideal_answer": [ "Yes. Tet2-TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. TETs are ubiquitously expressed and play diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. Depletion of Tet2 and its ligand, Tet3, from mouse CD4CD8 double-positive thymus-derived cardiomyocytes (iNKT) resulted in dysregulated development and proliferation, with increased expression of tumour suppressor genes and decreased", "Yes. TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR).", "Yes. Tet2-Tet3 double-knocked-out (DKO) iNKT cells displayed pronounced skew toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPok. Moreover, simultaneous deletion of Tet2 and Tet3 in mouse CD4CD8 double-positive thymocytes resulted in dysregulated development and proliferation of the non-classical major histocomponent complex (MHC) CD1d, which presents lipid antigens to T-cell-derived", "Yes. Tet2-Tet3 proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. Indeed, deletion of Tet2 and Tet3 in mouse CD4CD8 double-positive thymus cells resulted in dysregulated development and proliferation of the non-classical major histocompromised T cell antigen receptor (MHC) protein CD1d, which presents lipid antigens to iNKB-derived cells. Moreover, overexpression of TET1 and TET3 in Drosophila melanogaster T cells (iN", "Yes. Tet2-Tet3 double-knockout (DKO) cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Mutations in exon 2 interfere with the synthesis of the full-length isoform of Tet2 and lead to the production of a shortened isoform, Tet2s. These mutations have been found in human natural killer T cells (iNKTs), the most common type of innate immune cells." ], "exact_answer": "yes", "type": "yesno", "id": "5e36994092b3349b55000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869820", "endSection": "title" }, { "offsetInBeginSection": 102, "offsetInEndSection": 985, "text": "We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869820", "endSection": "title" } ] }, { "body": "What is the purpose of the Sunnybrook Facial Grading System?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25875477", "http://www.ncbi.nlm.nih.gov/pubmed/29987587", "http://www.ncbi.nlm.nih.gov/pubmed/27101446", "http://www.ncbi.nlm.nih.gov/pubmed/16942452", "http://www.ncbi.nlm.nih.gov/pubmed/18650612", "http://www.ncbi.nlm.nih.gov/pubmed/15806042", "http://www.ncbi.nlm.nih.gov/pubmed/20422701", "http://www.ncbi.nlm.nih.gov/pubmed/27832680", "http://www.ncbi.nlm.nih.gov/pubmed/29100751", "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "http://www.ncbi.nlm.nih.gov/pubmed/22487815", "http://www.ncbi.nlm.nih.gov/pubmed/27836742", "http://www.ncbi.nlm.nih.gov/pubmed/30377760", "http://www.ncbi.nlm.nih.gov/pubmed/28549753", "http://www.ncbi.nlm.nih.gov/pubmed/31365637" ], "ideal_answer": [ "The Sunnybrook facial grading system is applied to evaluate facial function in patients with facial palsy." ], "type": "summary", "id": "5e47568d3f5415952900001b", "snippets": [ { "offsetInBeginSection": 432, "offsetInEndSection": 615, "text": "The degree of synkinesis was evaluated at 6, 9 and 12 months after the onset of facial nerve palsy based on Sunnybrook facial grading system score and asymmetry in eye opening width. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29100751", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 779, "text": "Facial asymmetry was studied with the Sunnybrook facial grading system (SFGS), the Facial Clinimetric Evaluation Scale (FaCE), the Symmetry Scale for Hemifacial Spasm (SSHS) and a self-assessment scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29987587", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 560, "text": "Sunnybrook facial grading system was used to evaluate the functional results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30377760", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 511, "text": "MATERIALS AND METHODS: In this descriptive study, 27 patients (15 men and 12 women, mean age 48years) with unilateral peripheral facial palsy were included if they were graded under 70 on the Sunnybrook Facial Grading System.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27836742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Background: The Sunnybrook facial grading system (SFGS) is frequently applied to evaluate facial function in patients with facial palsy, but still now there is no validated German version of this evaluation sheet. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27832680", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1367, "text": "Discussion: There is now a valid German version of the SFGS available that can be used even by novices. The German version is suitable for evaluation of facial palsies in clinical routine and studies to allow a better comparability of German patients with results of the international literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27832680", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 598, "text": "We used tools for assessing impairment (Sunnybrook Facial Grading System [FGS]), psychological distress (Hospital Anxiety and Depression Scale [HADS]), disability (Facial Disability Index [FDI]), and quality of life (Facial Clinimetric Evaluation [FaCE] scale).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28549753", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 997, "text": "The rehabilitative protocol at the first clinical evaluation has been monitored through the Italian version of Sunnybrook Facial Grading System (SFGS) and the Software Facial Assessment by Computer Evaluation (FACE). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25875477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "IMPORTANCE: Most rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System (FGS) to measure and detect changes in facial function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27101446", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 344, "text": "The Sunnybrook Facial Grading System (SB) is a well-established tool for assessing facial movement outcomes; however, some ambiguities do arise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20422701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND\n\nThe Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Parotidectomy-related facial nerve lesions: proposal for a modified Sunnybrook Facial Grading System.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31365637", "endSection": "title" }, { "offsetInBeginSection": 798, "offsetInEndSection": 975, "text": "RESULTS\n\nAfter botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 316, "text": "To test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy, emphasizing the marginal mandibular branch.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31365637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "IMPORTANCE\n\nMost rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System (FGS) to measure and detect changes in facial function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27101446", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 756, "text": "Facial symmetry was measured using the Sunnybrook Facial Grading System.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16942452", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 747, "text": "Facial symmetry was measured using the Sunnybrook Facial Grading System.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16942452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The Sunnybrook Facial Grading System ( SFGS ) is one of the most employed scales to assess the severity of facial palsy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22487815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "The Sunnybrook facial grading system ( SFGS ) is frequently applied to evaluate facial function in patients with facial palsy , but still now there is no validated German version of this evaluation sheet.The original English version of the SFGS was translated and validated in accordance with international standards", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27832680", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 463, "text": "The aim of this study was to quantify eye synkinesis improvement after botulinum toxin type A injections using the new software and to compare this method with the Sunnybrook grading system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 308, "text": "To test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy , emphasizing the marginal mandibular branch", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31365637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Most rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System ( FGS ) to measure and detect changes in facial function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27101446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Quantitative measurement of evolution of postparetic ocular synkinesis treated with botulinum toxin type A. BACKGROUND\nThe Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "title" }, { "offsetInBeginSection": 281, "offsetInEndSection": 472, "text": "The aim of this study was to quantify eye synkinesis improvement after botulinum toxin type A injections using the new software and to compare this method with the Sunnybrook grading system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 975, "text": "RESULTS\nAfter botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Reliability of the \"Sydney,\" \"Sunnybrook,\" and \"House Brackmann\" facial grading systems to assess voluntary movement and synkinesis after facial nerve paralysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15806042", "endSection": "title" }, { "offsetInBeginSection": 199, "offsetInEndSection": 344, "text": "The Sunnybrook Facial Grading System (SB) is a well-established tool for assessing facial movement outcomes; however, some ambiguities do arise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20422701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND: The Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 971, "text": "RESULTS: After botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 321, "text": "The Sunnybrook Facial Grading System (SB) is a well-established tool for assessing facial movement outcomes; however, some ambiguities do arise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20422701", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 943, "text": "After botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24165606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The Sunnybrook Facial Grading System (SFGS) is one of the most employed scales to assess the severity of facial palsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22487815", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 898, "text": "The mean Sunnybrook Facial Grading System score was 74 indicating adequate facial functioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18650612", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1608, "text": "The modified Sunnybrook Facial Grading System improved the marginal mandibular branch assessment, preserving the evaluation of other facial nerve branches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31365637", "endSection": "abstract" } ] }, { "body": "What is the function of the PDZ domain in SATB1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18187506", "http://www.ncbi.nlm.nih.gov/pubmed/11463840", "http://www.ncbi.nlm.nih.gov/pubmed/21799257" ], "ideal_answer": [ "N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator. We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins. PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1.", "N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator. Binding studies using HD-lacking SATB1 and binding target with increased spacer between the two half-sites led us to propose a model for SATB1-DNA complex in which the HDs bind in an antiparallel fashion to the palindromic consensus element via minor groove, bridged by the PDZ-like dimerization domain SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis. PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1. These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins. We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. ", "PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1.", "We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis. PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1. Binding studies using HD-lacking SATB1 and binding target with increased spacer between the two half-sites led us to propose a model for SATB1-DNA complex in which the HDs bind in an antiparallel fashion to the palindromic consensus element via minor groove, bridged by the PDZ-like dimerization domain N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator. These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins.", "We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis.", "The PDZ domain is a cytoplasmic protein domain found in histone H3 lysine 27 and it is essential for PDZ-mediated ubiquitination of SATB1." ], "type": "summary", "id": "5d36b5087bc3fee31f000008", "snippets": [ { "offsetInBeginSection": 963, "offsetInEndSection": 1145, "text": "We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11463840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11463840", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18187506", "endSection": "title" }, { "offsetInBeginSection": 676, "offsetInEndSection": 978, "text": "Binding studies using HD-lacking SATB1 and binding target with increased spacer between the two half-sites led us to propose a model for SATB1-DNA complex in which the HDs bind in an antiparallel fashion to the palindromic consensus element via minor groove, bridged by the PDZ-like dimerization domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18187506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21799257", "endSection": "title" }, { "offsetInBeginSection": 1614, "offsetInEndSection": 1771, "text": "These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21799257", "endSection": "abstract" } ] }, { "body": "What cellular process is the protein clathrin involved in?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26206992", "http://www.ncbi.nlm.nih.gov/pubmed/2475643", "http://www.ncbi.nlm.nih.gov/pubmed/28814502", "http://www.ncbi.nlm.nih.gov/pubmed/28117435", "http://www.ncbi.nlm.nih.gov/pubmed/27028652", "http://www.ncbi.nlm.nih.gov/pubmed/6310570", "http://www.ncbi.nlm.nih.gov/pubmed/23384308", "http://www.ncbi.nlm.nih.gov/pubmed/19793827", "http://www.ncbi.nlm.nih.gov/pubmed/6888541", "http://www.ncbi.nlm.nih.gov/pubmed/29035746", "http://www.ncbi.nlm.nih.gov/pubmed/29511054" ], "ideal_answer": [ "Clathrin is a central regulator of endocytosis in all eukaryotes that plays a role in bacterial and plastid differentiation", "Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes). while clathrin mediated endocytosis w", "Clathrin is a central regulator of endocytosis in all eukaryotes that plays a critical role in the maintenance of cellular homeostasis", "while clathrin mediated endocytosis w. Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes).", "Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes)", "Clathrin plays a critical role in endocytosis and in doing so is crucial for maintaining cellular homeostasis", "Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes).", "Clathrin plays a critical role in endocytosis and in many other cellular processes" ], "exact_answer": [ "receptor mediated endocytosis" ], "type": "factoid", "id": "5e4fd44a6d0a277941000033", "snippets": [ { "offsetInBeginSection": 50, "offsetInEndSection": 169, "text": "ligand-receptor complexes are internalized via clathrin coated pits by a process called receptor-mediated endocytosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6888541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6310570", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 768, "text": "while clathrin mediated endocytosis w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29035746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Clathrin is involved in the endocytosis and exocytosis of cellular proteins and the process of virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793827", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Endocytosis is a crucial cellular process in eukaryotic cells which involves clathrin and/or adaptor proteins , lipid kinases , phosphatases and the actin cytoskeleton", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28117435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Clathrin-independent endocytosis ( CIE ) is the process of cellular uptake of various particles , including pathogens , without the coat protein clathrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26206992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Endocytosis is an essential cellular process in eukaryotic cells that involves concordant functions of clathrin and adaptor proteins , various protein and lipid kinases , phosphatases and the actin cytoskeleton", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23384308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Endocytosis mediated by clathrin , a cellular process by which cells internalize membrane receptors and their extracellular ligands , is an important component of cell signaling regulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27028652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Clathrin-mediated endocytosis ( CME ) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Clathrin plays an important role in many cellular processes, including endocytosis, secretion, and sorting of membranous organelles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2475643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28814502", "endSection": "abstract" } ] }, { "body": "Thymoquinone is ineffective against radiation induced enteritis, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30310156" ], "ideal_answer": [ "No, Thymoquinone has been found to be effective against radiation induced enteritis", "n this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. ", "thymoquinone (tq ) could mitigate intestinal damages induced by irradiation", "n this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation." ], "exact_answer": "no", "type": "yesno", "id": "5e3c80abb5b409ea53000024", "snippets": [ { "offsetInBeginSection": 157, "offsetInEndSection": 261, "text": "n this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30310156", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 260, "text": "In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30310156", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 261, "text": "In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30310156", "endSection": "abstract" }, { "offsetInBeginSection": 786, "offsetInEndSection": 837, "text": "TQ might be used for radiation enteritis treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30310156", "endSection": "abstract" } ] }, { "body": "Which are the databases for intrinsic protein disorders?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29136219", "http://www.ncbi.nlm.nih.gov/pubmed/23815411", "http://www.ncbi.nlm.nih.gov/pubmed/22661649", "http://www.ncbi.nlm.nih.gov/pubmed/28968848" ], "ideal_answer": [ "Intrinsic disorder (ID), i.e. the lack of a unique folded conformation at physiological conditions, is a common feature for many proteins, which requires specialized biochemical experiments that are not high-throughput. DisProt and MobiDB are databases for intrinsic protein disorders." ], "exact_answer": [ [ "DisProt" ], [ "MobiDB" ] ], "type": "list", "id": "5e5015436d0a277941000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "A comprehensive assessment of long intrinsic protein disorder from the DisProt database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968848", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1589, "text": "Intrinsic disorder (ID), i.e. the lack of a unique folded conformation at physiological conditions, is a common feature for many proteins, which requires specialized biochemical experiments that are not high-throughput. Missing X-ray residues from the PDB have been widely used as a proxy for ID when developing computational methods. This may lead to a systematic bias, where predictors deviate from biologically relevant ID. Large benchmarking sets on experimentally validated ID are scarce. Recently, the DisProt database has been renewed and expanded to include manually curated ID annotations for several hundred new proteins. This provides a large benchmark set which has not yet been used for training ID predictors.Results: Here, we describe the first systematic benchmarking of ID predictors on the new DisProt dataset. In contrast to previous assessments based on missing X-ray data, this dataset contains mostly long ID regions and a significant amount of fully ID proteins. The benchmarking shows that ID predictors work quite well on the new dataset, especially for long ID segments. However, a large fraction of ID still goes virtually undetected and the ranking of methods is different than for PDB data. In particular, many predictors appear to confound ID and regions outside X-ray structures. This suggests that the ID prediction methods capture different flavors of disorder and can benefit from highly accurate curated examples.Availability and implementation: The raw data used for the evaluation are available from URL: http://www.disprot.org/assessment/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "MobiDB: a comprehensive database of intrinsic protein disorder annotations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661649", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1230, "text": "Disordered protein regions are key to the function of numerous processes within an organism and to the determination of a protein's biological role. The most common source for protein disorder annotations, DisProt, covers only a fraction of the available sequences. Alternatively, the Protein Data Bank (PDB) has been mined for missing residues in X-ray crystallographic structures. Herein, we provide a centralized source for data on different flavours of disorder in protein structures, MobiDB, building on and expanding the content provided by already existing sources. In addition to the DisProt and PDB X-ray structures, we have added experimental information from NMR structures and five different flavours of two disorder predictors (ESpritz and IUpred). These are combined into a weighted consensus disorder used to classify disordered regions into flexible and constrained disorder. Users are encouraged to submit manual annotations through a submission form. MobiDB features experimental annotations for 17 285 proteins, covering the entire PDB and predictions for the SwissProt database, with 565 200 annotated sequences. Depending on the disorder flavour, 6-20% of the residues are predicted as disordered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The MobiDB (URL: mobidb.bio.unipd.it) database of protein disorder and mobility annotations has been significantly updated and upgraded since its last major renewal in 2014.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Analysis and consensus of currently available intrinsic protein disorder annotation sources in the MobiDB database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815411", "endSection": "title" }, { "offsetInBeginSection": 396, "offsetInEndSection": 536, "text": "Our recently published database, MobiDB, provides a centralized resource for accessing and analysing intrinsic protein disorder annotations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815411", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 534, "text": "Our recently published database , MobiDB , provides a centralized resource for accessing and analysing intrinsic protein disorder annotations .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "MobiDB: a comprehensive database of intrinsic protein disorder annotations .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661649", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "A comprehensive assessment of long intrinsic protein disorder from the DisProt database .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968848", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Analysis and consensus of currently available intrinsic protein disorder annotation sources in the MobiDB database .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815411", "endSection": "title" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1242, "text": "A large amount of information and cross-links to more specialized databases are intended to make MobiDB the central resource for the scientific community working on protein intrinsic disorder and mobility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136219", "endSection": "abstract" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1383, "text": "MobiDB is a central resource for intrinsic disorder research, containing both experimental data and predictions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815411", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 265, "text": "The most common source for protein disorder annotations, DisProt, covers only a fraction of the available sequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661649", "endSection": "abstract" } ] }, { "body": "List the 5 different human immunoglobulin heavy chains.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23105285", "http://www.ncbi.nlm.nih.gov/pubmed/23105292", "http://www.ncbi.nlm.nih.gov/pubmed/16148123" ], "ideal_answer": [ "The 5 human immunoglobulin heavy chains are Alpha, Delta Epsilon, Gamma and Mu", "using heavy chain specific gamma, alpha, mu, delta and epsilon" ], "exact_answer": [ [ "alpha" ], [ "delta" ], [ "epsilon" ], [ "gamma" ], [ "mu" ] ], "type": "list", "id": "5e4f0a4f6d0a277941000031", "snippets": [ { "offsetInBeginSection": 329, "offsetInEndSection": 433, "text": ". Despite this, Ag-specific single H chain Ig repertoires, using mu-, gamma-, epsilon-, or alpha-H chain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16148123", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 219, "text": "he neoplastic proliferation of single clones of plasma cells causes synthesis of very large amount of monoclonal immunoglobulins consisting of only one type of heavy either the gamma, alpha, mu, delta or epsilon chain ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23105285", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 499, "text": "using heavy chain specific gamma, alpha, mu, delta and epsilon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23105292", "endSection": "abstract" } ] }, { "body": "Has the Spanich flu virus been reconstructed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30142572", "http://www.ncbi.nlm.nih.gov/pubmed/22967978", "http://www.ncbi.nlm.nih.gov/pubmed/19385726" ], "ideal_answer": [ "Tes,\nReconstruction of the 1918 influenza virus has facilitated considerable advancements in our understanding of this extraordinary pandemic virus." ], "exact_answer": "yes", "type": "yesno", "id": "5e5d27531af46fc130000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Reconstruction of the 1918 influenza virus has facilitated considerable advancements in our understanding of this extraordinary pandemic virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142572", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 723, "text": "These viral RNA sequences eventually permitted reconstruction of the complete 1918 virus, which has yielded, almost a century after the deaths of its victims, novel insights into influenza virus biology and pathogenesis and has provided important information about how to prevent and control future pandemics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22967978", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 441, "text": "Reconstruction of the 1918 virus and studies elucidating the exceptional virulence and transmissibility of the virus are providing exciting new insights into this devastating pandemic strain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19385726", "endSection": "abstract" } ] }, { "body": "What is the basis of the BLISS technique?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29443107", "http://www.ncbi.nlm.nih.gov/pubmed/28497783", "http://www.ncbi.nlm.nih.gov/pubmed/29043625" ], "ideal_answer": [ "Here we present Breaks Labeling In Situ and Sequencing (BLISS), a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.", "Breaks Labeling In Situ and Sequencing (BLISS) is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.", "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. A recent method, BLISS, uses photoreactive nucleotides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation.", "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.", "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. Recently, we have further expanded the quantitative nature, applicability, and scalability of BLESS by developing Breaks Labeling In Situ and Sequencing (BLISS). Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing.", "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing.", "bliss is a versatile and quantitative method for genome-wide profiling of dna double-strand breaks", "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing. Recently, we have further expanded the quantitative nature, applicability, and scalability of BLESS by developing Breaks Labeling In Situ and Sequencing (BLISS)", "BLISS (Breaks Labeling In Situ and Sequencing) is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks (DSBs). It uses a novel Bayesian approach which represents continuous allele frequencies for both the endogenous and endogenous DSBs, while leveraging the endogenous Cpf1 methyltransferase activity of the zinc cluster as a template." ], "type": "summary", "id": "5d35ebe7b3a6380763000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28497783", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 599, "text": "Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28497783", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 1024, "text": "Recently, we have further expanded the quantitative nature, applicability, and scalability of BLESS by developing Breaks Labeling In Situ and Sequencing (BLISS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29043625", "endSection": "abstract" } ] }, { "body": "List 3 NK3R antagonists.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28977601", "http://www.ncbi.nlm.nih.gov/pubmed/26653113", "http://www.ncbi.nlm.nih.gov/pubmed/28380486", "http://www.ncbi.nlm.nih.gov/pubmed/27636018" ], "ideal_answer": [ "NK3 receptor antagonists include MLE4901 (also known as AZD4901), SB222200 and ESN364." ], "exact_answer": [ [ "MLE4901", "AZD4901" ], [ "SB222200" ], [ "ESN364" ] ], "type": "list", "id": "5e55046fb761aafe09000004", "snippets": [ { "offsetInBeginSection": 344, "offsetInEndSection": 457, "text": "Eleven postmenopausal women were administered the NK3R antagonist MLE4901 at 40 mg twice daily orally for 7 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28380486", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 1225, "text": "Results indicate that (1) similar to those previously reported for GnRH stimulation by the KISS1R agonist (i.e., human kisspeptin-10), the NK3R agonist senktide stimulated GnRH release in a dose-responsive manner in both prepubertal and pubertal monkeys; (2) the senktide-induced GnRH release was blocked in the presence of the KISS1R antagonist peptide 234 in pubertal but not prepubertal monkeys; and (3) the kisspeptin-induced GnRH release was blocked in the presence of the NK3R antagonist SB222200 in the pubertal but not prepubertal monkeys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28977601", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 738, "text": "NK3R antagonist AZD4901 40 mg twice daily orally was taken from cycle day 4-6 for 6 days (n = 10, with 10 no treatment controls). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27636018", "endSection": "abstract" }, { "offsetInBeginSection": 1797, "offsetInEndSection": 2043, "text": " Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653113", "endSection": "abstract" } ] }, { "body": "Is Verubecestat effective for Alzheimer's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31423903", "http://www.ncbi.nlm.nih.gov/pubmed/31387606", "http://www.ncbi.nlm.nih.gov/pubmed/28749667", "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "http://www.ncbi.nlm.nih.gov/pubmed/30970186", "http://www.ncbi.nlm.nih.gov/pubmed/30347431" ], "ideal_answer": [ "No. Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events." ], "exact_answer": "no", "type": "yesno", "id": "5e3a6c49b5b409ea53000017", "snippets": [ { "offsetInBeginSection": 351, "offsetInEndSection": 551, "text": "The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28749667", "endSection": "abstract" }, { "offsetInBeginSection": 2341, "offsetInEndSection": 2525, "text": "CONCLUSIONS: Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1099, "text": "These results support the continued global development of verubecestat as a potential disease-modifying agent for Japanese and non-Japanese subjects who are at-risk for developing AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30347431", "endSection": "abstract" }, { "offsetInBeginSection": 2347, "offsetInEndSection": 2531, "text": "CONCLUSIONS\n\nVerubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "endSection": "abstract" }, { "offsetInBeginSection": 2305, "offsetInEndSection": 2579, "text": "CONCLUSIONS\n\nVerubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30970186", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 485, "text": "However, in the EPOCH trial of verubecestat in mild-to-moderate Alzheimer's disease, it was not beneficial and increased adverse effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423903", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 731, "text": "In APECS, verubecestat 40 mg worsened cognition and increased adverse effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423903", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 561, "text": "The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors , and anti-amyloid therapies in general , in AD treatment . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28749667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Verubecestat , a BACE1 inhibitor that reduces A\u03b2 levels in the cerebrospinal fluid of humans , was not effective in a phase 3 trial ( EPOCH ) of mild-to-moderate AD and was associated with adverse events . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31387606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Lessons that can be learnt from the failure of verubecestat in Alzheimer 's disease .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423903", "endSection": "title" }, { "offsetInBeginSection": 2305, "offsetInEndSection": 2579, "text": "CONCLUSIONS\nVerubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30970186", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 944, "text": "In APECS, verubecestat 40 mg worsened cognition and increased adverse effects.Expert opinion: In recruiting subjects to clinical trials in Alzheimer's disease, a clinical diagnosis involving the measurement of A\u03b2 should be undertaken for all subjects, as this may help to clarify the findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423903", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1136, "text": "In my opinion, the failure of verubecestat in EPOCH and APECS probably could have been avoided if a safety and potential efficacy trial (phase 2) had been completed prior to starting phase 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423903", "endSection": "abstract" }, { "offsetInBeginSection": 1480, "offsetInEndSection": 1577, "text": "CONCLUSIONS: Verubecestat was associated with increased risk for several types of adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31387606", "endSection": "abstract" }, { "offsetInBeginSection": 2272, "offsetInEndSection": 2535, "text": "Verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo. (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30970186", "endSection": "abstract" }, { "offsetInBeginSection": 2314, "offsetInEndSection": 2487, "text": "Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719179", "endSection": "abstract" } ] }, { "body": "Is Aptiganel effective for treatment of stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12917902", "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "http://www.ncbi.nlm.nih.gov/pubmed/12849400", "http://www.ncbi.nlm.nih.gov/pubmed/12365832" ], "ideal_answer": [ "No. Aptiganel is not efficacious in patients with acute ischemic stroke and may be harmful." ], "exact_answer": "no", "type": "yesno", "id": "5e44c76f48dab47f26000022", "snippets": [ { "offsetInBeginSection": 3328, "offsetInEndSection": 3774, "text": "Trends for increased mortality with three NMDA antagonists were seen - selfotel (OR 1.19 [0.81-1.74]), aptiganel (OR 1.32 [0.91-1.93]) and gavestinel (OR 1.12 [0.95-1.32]) - but this did not achieve significance for the NMDA antagonists considered as a class (1.09 [0.96-1.23]). Aptiganel was also associated with a trend towards worse functional outcome (OR 1.20 [0.88-1.65]) although this was not the case for either of the other two compounds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12917902", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 608, "text": "No improvement in clinical outcome of stroke has been seen with competitive NMDA antagonists (selfotel) and non-competitive NMDA antagonists (dextrorphan, GV150526, aptiganel and eliprodil).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12365832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12849400", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 2136, "text": "There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, -0.8 points vs for high-dose aptiganel, 0.9 points; P =.04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P =.06).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 2209, "offsetInEndSection": 2576, "text": "CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 2225, "offsetInEndSection": 2358, "text": "CONCLUSIONS\n\nAptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 2359, "offsetInEndSection": 2592, "text": "The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1750, "text": "There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12849400", "endSection": "abstract" }, { "offsetInBeginSection": 2209, "offsetInEndSection": 2341, "text": "CONCLUSIONS Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Glutamate N-methyl-D-aspartate ( NMDA ) receptor antagonists ( competitive receptor antagonists , ion channel blockers , and glycine antagonists)--such as selfotel , aptiganel , eliprodil , licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12849400", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 619, "text": "No improvement in clinical outcome of stroke has been seen with competitive NMDA antagonists ( selfotel ) and non-competitive NMDA antagonists ( dextrorphan , GV150526 , aptiganel and eliprodil", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12365832", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1750, "text": "There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 2209, "offsetInEndSection": 2342, "text": "CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 2343, "offsetInEndSection": 2576, "text": "The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 1439, "offsetInEndSection": 1645, "text": "There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 2119, "offsetInEndSection": 2239, "text": "Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" }, { "offsetInBeginSection": 2240, "offsetInEndSection": 2473, "text": "The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11730442", "endSection": "abstract" } ] }, { "body": "Is indinavir effective for treatment of amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15824372" ], "ideal_answer": [ "No, indinavir is not effective for treatment of amyotrophic lateral sclerosis." ], "exact_answer": "no", "type": "yesno", "id": "5e47656935b8f0833c000004", "snippets": [ { "offsetInBeginSection": 270, "offsetInEndSection": 515, "text": "Group differences in the rate of decline were not significant between the groups for the ALS Functional Rating Scale (p = 0.36) or for the secondary variables. The toxicity and negative efficacy trends discourage further indinavir trials in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15824372", "endSection": "abstract" } ] }, { "body": "Is there an increased risk for meningiomas in childhood leukemia survivors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23459379", "http://www.ncbi.nlm.nih.gov/pubmed/30880270", "http://www.ncbi.nlm.nih.gov/pubmed/16193392", "http://www.ncbi.nlm.nih.gov/pubmed/17243137", "http://www.ncbi.nlm.nih.gov/pubmed/23690411", "http://www.ncbi.nlm.nih.gov/pubmed/17190987", "http://www.ncbi.nlm.nih.gov/pubmed/19179425", "http://www.ncbi.nlm.nih.gov/pubmed/24767145", "http://www.ncbi.nlm.nih.gov/pubmed/20634481", "http://www.ncbi.nlm.nih.gov/pubmed/20207611", "http://www.ncbi.nlm.nih.gov/pubmed/28775249", "http://www.ncbi.nlm.nih.gov/pubmed/21671360", "http://www.ncbi.nlm.nih.gov/pubmed/22522336" ], "ideal_answer": [ "Yes, the risk of meningiomas is higher in children treated with cranial irradiation for leukemia." ], "exact_answer": "yes", "type": "yesno", "id": "5e324167fbd6abf43b00005a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Cranial radiotherapy improves survival of the most common childhood cancers, including brain tumors and leukemia. Unfortunately, long-term survivors are faced with consequences of secondary neoplasia, including radiation-induced meningiomas (RIMs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28775249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "Combined chemotherapy and prophylactic cranial irradiation has improved the prognosis of children with acute leukemia. However cranial irradiation carries a latent risk of the induction of secondary intracranial tumors. We encountered a patient who developed multiple intracranial radiation-induced meningiomas (RIMs) 25\u00a0years after prophylactic cranial irradiation for the treatment of acute leukemia in childhood. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24767145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Focal cranial hyperostosis from meningioma: a complication from previous radiation treatment for childhood T-cell acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23459379", "endSection": "title" }, { "offsetInBeginSection": 233, "offsetInEndSection": 756, "text": "Presented is a case of a 20 year man with a history of T-cell lymphoblastic leukemia diagnosed at age 22 months, treated with chemotherapy and cranial irradiation. He had developed increasing prominence of the top of his head over several months. Plain radiograph showed frontal calvarium thickening with focal \"hair-on-end\" periosteal reaction. Magnetic resonance imaging revealed an enhancing dural-based mass with transcalvarial extension, confirmed after resection to be meningioma (World Health Organization Grade I). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23459379", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 583, "text": "RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% \u00b1 2.9%, 31.1% \u00b1 6.2%, and 18.3% \u00b1 3.8%, respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23690411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood. Three case reports.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 1075, "text": "RESULTS: Fifty-nine MRI abnormalities (32 cavernomas, nine focal areas of gliosis, seven dystrophic mineralizations, five cerebral atrophies, four pituitary atrophies, one diffuse radiation leukoencephalopathy, and one meningioma) were found in 43 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21671360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Intraventricular meningioma after cranial irradiation for childhood leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20207611", "endSection": "title" }, { "offsetInBeginSection": 484, "offsetInEndSection": 701, "text": "Radiation-induced meningiomas may also have predilection to recur. The authors describe a case of an intraventricular meningioma occurring 23 years after cranial irradiation for childhood acute lymphoblastic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20207611", "endSection": "abstract" }, { "offsetInBeginSection": 1015, "offsetInEndSection": 1378, "text": "Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20634481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Radiation-induced meningiomas: a shadow in the success story of childhood leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19179425", "endSection": "title" }, { "offsetInBeginSection": 1418, "offsetInEndSection": 1576, "text": "Although the cohort is small, it seems probable that the increasing incidence of meningioma will shadow the future of cranially irradiated leukemia survivors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19179425", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1325, "text": "Age at the time of irradiation, gender, or cumulative doses of chemotherapeutic agents showed no significant association with the development of meningiomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19179425", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Meningioma Screening With MRI in Childhood Leukemia Survivors Treated With Cranial Radiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30880270", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17243137", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Radiation-induced meningioma following prophylactic radiotherapy for acute lymphoblastic leukemia in childhood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17190987", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia ( ALL) , but have resulted in an increased risk of late central nervous system tumors , most commonly meningioma , particularly in patients who have received cranial irradiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 723, "text": "Survivors of childhood ALL treated with high-dose cranial irradiation are at risk both for early radiation injury in radiosensitive organs , such as the lens and pituitary gland , and for the later development of a radiation-induced meningioma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16193392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Radiation-induced meningiomas: a shadow in the success story of childhood leukemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19179425", "endSection": "title" }, { "offsetInBeginSection": 299, "offsetInEndSection": 617, "text": "We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman , a petroclival tumor in a 28-year-old man , and a frontal parasagittal tumor in a 19-year-old woman", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 612, "text": "We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman, a petroclival tumor in a 28-year-old man, and a frontal parasagittal tumor in a 19-year-old woman.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522336", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1179, "text": "Long-term survivors who received radiotherapy for ALL in childhood are at risk for late complications, including radiation-induced meningioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17190987", "endSection": "abstract" } ] }, { "body": "List the clinical characteristics of the Smith-Kingsmore syndrome (SKS)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28892148", "http://www.ncbi.nlm.nih.gov/pubmed/31053780" ], "ideal_answer": [ "Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features.", "Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. " ], "exact_answer": [ [ "Intellectual disability" ], [ "macrocephaly/hemi/megalencephaly" ], [ "seizures" ], [ "facial dysmorphology" ], [ "other non-neurological features" ] ], "type": "list", "id": "5e51c6036d0a27794100003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28892148", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 256, "text": "SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28892148", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 864, "text": "GOF variants in this protein have been associated with Smith-Kingsmore syndrome (SKS), a rare autosomal dominant disorder characterized by intellectual disability, macrocephaly, seizure, developmental delay and dysmorphic facial features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31053780", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 888, "text": "GOF variants in this protein have been associated with Smith-Kingsmore syndrome ( SKS) , a rare autosomal dominant disorder characterized by intellectual disability , macrocephaly , seizure , developmental delay and dysmorphic facial features", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31053780", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 257, "text": "SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28892148", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 865, "text": "GOF variants in this protein have been associated with Smith-Kingsmore syndrome (SKS), a rare autosomal dominant disorder characterized by intellectual disability, macrocephaly, seizure, developmental delay and dysmorphic facial features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31053780", "endSection": "abstract" } ] }, { "body": "What is ORMD-0801?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23593142" ], "ideal_answer": [ "ORMD-0801 is an oral insulin capsule. Treatment with ORMD-0801 was associated with a significant 24.4% reduction in the frequencies of glucose readings >200 mg/dL (60.1 +- 7.9% pretreatment vs. 45.4 +- 4.9% during ORMD-0801 treatment; p = 0.023) and a significant mean 16.6% decrease in glucose area under the curve (AUC) (66055 +- 5547 mg/dL/24 hours vs. 55060 +- 3068 mg/dL/24 hours, p = 0.023), with a greater decrease during the early evening hours. When used in conjunction with subcutaneous insulin injections, ORMD-0801 was well tolerated and effectively reduced glycemia throughout the day." ], "type": "summary", "id": "5e763366c6a8763d2300000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Glucose-reducing effect of the ORMD-0801 oral insulin preparation in patients with uncontrolled type 1 diabetes: a pilot study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593142", "endSection": "title" }, { "offsetInBeginSection": 392, "offsetInEndSection": 606, "text": " In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin) in addressing this resistant clinical state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593142", "endSection": "abstract" }, { "offsetInBeginSection": 1182, "offsetInEndSection": 1761, "text": "Treatment with ORMD-0801 was associated with a significant 24.4% reduction in the frequencies of glucose readings >200 mg/dL (60.1 \u00b1 7.9% pretreatment vs. 45.4 \u00b1 4.9% during ORMD-0801 treatment; p\u200a=\u200a0.023) and a significant mean 16.6% decrease in glucose area under the curve (AUC) (66055 \u00b1 5547 mg/dL/24 hours vs. 55060 \u00b1 3068 mg/dL/24 hours, p\u200a=\u200a0.023), with a greater decrease during the early evening hours. In conclusion, ORMD-0801 oral insulin capsules in conjunction with subcutaneous insulin injections, well tolerated and effectively reduced glycemia throughout the day.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593142", "endSection": "abstract" } ] }, { "body": "Does saracatinib promote oncogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23144237" ], "ideal_answer": [ "No, saracatinib has antitumor activity." ], "exact_answer": "no", "type": "yesno", "id": "5e540ed36d0a277941000054", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144237", "endSection": "title" }, { "offsetInBeginSection": 459, "offsetInEndSection": 939, "text": "We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G(1) arrest and apoptosis in SNU216 and NCI-N87 cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144237", "endSection": "abstract" }, { "offsetInBeginSection": 1460, "offsetInEndSection": 1767, "text": "Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23144237", "endSection": "abstract" } ] }, { "body": "Is BCL11B involved in schizophrenia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30040823" ], "ideal_answer": [ "Yes, BCL11B is associated with attention, memory, executive function and antipsychotic-induced schizophrenia.", "Yes. SATB2 is associated with schizophrenia and is an important transcription factor regulating neocortical organization and circuitry. Rare mutations in SATB2 cause a syndrome that includes developmental delay, and mouse studies identify an important role for SATB2 in learning and memory. Interacting partners BCL11B and GATAD2A are also schizophrenia risk genes.", "Yes. Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with schizophrenia, including BCL11B, a master regulator of cortical development, in patients with schizophrenia. BCL 11B is involved in the development of the central nervous system, and its deficiency or pharmacological neutralization may contribute to the onset of schizophrenia.", "Yes. BCL11B is a transcriptional repressor essential for schizophrenia.", "Yes. BCL11B is associated with early as well as with late onset schizophrenia." ], "exact_answer": "yes", "type": "yesno", "id": "5e2e0fa2fbd6abf43b00001f", "snippets": [ { "offsetInBeginSection": 289, "offsetInEndSection": 493, "text": "Interacting partners BCL11B and GATAD2A are also schizophrenia risk genes indicating that other genes interacting with or are regulated by SATB2 are making a contribution to schizophrenia and cognition . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30040823", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 489, "text": "Interacting partners BCL11B and GATAD2A are also schizophrenia risk genes indicating that other genes interacting with or are regulated by SATB2 are making a contribution to schizophrenia and cognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30040823", "endSection": "abstract" } ] }, { "body": "What is Synucleinopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31698547", "http://www.ncbi.nlm.nih.gov/pubmed/26306821", "http://www.ncbi.nlm.nih.gov/pubmed/28751258", "http://www.ncbi.nlm.nih.gov/pubmed/28910367", "http://www.ncbi.nlm.nih.gov/pubmed/27875637", "http://www.ncbi.nlm.nih.gov/pubmed/26948950", "http://www.ncbi.nlm.nih.gov/pubmed/19378813", "http://www.ncbi.nlm.nih.gov/pubmed/29185072" ], "ideal_answer": [ "Synucleinopathy is an autosomal-dominant disease characterised by misfolding of presynaptic synuclein and the formation of Lewy bodies with ubiquitin-ligase activity.", "Synucleinopathies (also called a-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells.", "Synucleinopathy is an autosomal recessive neurodegenerative disease characterized by the degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy neurites in central nervous system", "Synucleinopathy is an autosomal recessive neurodegenerative disease characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies in a proportion of the remaining neurones.", "The accumulation of abnormal a-synuclein is the major histopathological feature of Lewy body disease and multiple system atrophy (MSA), which are referred to as synucleinopathies." ], "type": "summary", "id": "5e40260f48dab47f2600000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 401, "text": "The deposition of misfolded \u03b2-sheet enriched amyloid protein is a shared feature of many neurodegenerative diseases. Recent studies demonstrated the existence of conformationally diverse strains as a common property for multiple amyloidogenic proteins including \u03b1-Synuclein (\u03b1-Syn). \u03b1-Syn is misfolded and aggregated in a group of neurodegenerative diseases collectively known as \u03b1-Synucleinopathies, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28751258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The accumulation of abnormal \u03b1-synuclein is the major histopathological feature of Lewy body disease and multiple system atrophy (MSA), which are referred to as synucleinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27875637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The abnormal accumulation of \u03b1-synuclein aggregates in neurons, nerve fibers, or glial cells is the hallmark of a group of neurodegenerative diseases known collectively as \u03b1-synucleinopathies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29185072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "BACKGROUND\n\nSynucleinopathy is any of a group of age-related neurodegenerative disorders including Parkinson's disease, multiple system atrophy, and dementia with Lewy Bodies, which is characterized by \u03b1-synuclein inclusions and parkinsonian motor deficits affecting millions of patients worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26306821", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 572, "text": "Alpha-synucleinopathy is a term that collectively refers to a set of diseases in which neurodegeneration is accompanied by intracellular accumulation of alpha-synuclein in neurons or glial cells . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19378813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "BACKGROUND: Synucleinopathy is any of a group of age-related neurodegenerative disorders including Parkinson's disease, multiple system atrophy, and dementia with Lewy Bodies, which is characterized by \u03b1-synuclein inclusions and parkinsonian motor deficits affecting millions of patients worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26306821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Synucleinopathies are neurodegenerative disorders characterized by the progressive accumulation of \u03b1-synuclein (\u03b1-syn) in neurons and glia and include Parkinson's disease (PD) and dementia with Lewy bodies (DLB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31698547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Synucleinopathies are a spectrum of neurodegenerative diseases characterized by the intracellular deposition of the protein \u03b1-synuclein leading to multiple outcomes, including dementia and Parkinsonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28910367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Synucleinopathies are a group of neurodegenerative diseases that share a common pathological lesion of intracellular protein inclusions largely composed by aggregates of alpha-synuclein protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26948950", "endSection": "abstract" } ] }, { "body": "Which receptor is modulated with Siponimod?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24900670", "http://www.ncbi.nlm.nih.gov/pubmed/29627873", "http://www.ncbi.nlm.nih.gov/pubmed/25580263", "http://www.ncbi.nlm.nih.gov/pubmed/29500302", "http://www.ncbi.nlm.nih.gov/pubmed/31558140", "http://www.ncbi.nlm.nih.gov/pubmed/28990207", "http://www.ncbi.nlm.nih.gov/pubmed/29576505", "http://www.ncbi.nlm.nih.gov/pubmed/31603362", "http://www.ncbi.nlm.nih.gov/pubmed/31290453", "http://www.ncbi.nlm.nih.gov/pubmed/25924727", "http://www.ncbi.nlm.nih.gov/pubmed/29310513", "http://www.ncbi.nlm.nih.gov/pubmed/26856814", "http://www.ncbi.nlm.nih.gov/pubmed/23764350", "http://www.ncbi.nlm.nih.gov/pubmed/29110882", "http://www.ncbi.nlm.nih.gov/pubmed/31009359", "http://www.ncbi.nlm.nih.gov/pubmed/29138536", "http://www.ncbi.nlm.nih.gov/pubmed/29205338", "http://www.ncbi.nlm.nih.gov/pubmed/29556671", "http://www.ncbi.nlm.nih.gov/pubmed/25223691", "http://www.ncbi.nlm.nih.gov/pubmed/31144287", "http://www.ncbi.nlm.nih.gov/pubmed/28752787", "http://www.ncbi.nlm.nih.gov/pubmed/29735753", "http://www.ncbi.nlm.nih.gov/pubmed/27566665" ], "ideal_answer": [ "Siponimod is a functional sphingosine-1-phosphate (S1P) antagonist." ], "exact_answer": [ "sphingosine-1-phosphate" ], "type": "factoid", "id": "5e48a916d14c9f295d00000f", "snippets": [ { "offsetInBeginSection": 907, "offsetInEndSection": 1076, "text": "RESULTS: Among a battery of molecules tested, siponimod, a dual agonist of sphingosine-1-phosphate receptor 1 and 5, was among the most efficient favoring remyelination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28752787", "endSection": "abstract" }, { "offsetInBeginSection": 1322, "offsetInEndSection": 1493, "text": "We validated several known promyelinating compounds and demonstrated that the strong remyelinating efficacy of siponimod implicates the sphingosine-1-phosphate receptor 5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28752787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 363, "text": "Sphingosine 1-phosphate (S1P1 ) modulators provide an emerging therapeutic approach for various autoimmune disorders such as multiple sclerosis and psoriasis. Fingolimod is the first approved orally active, selective and potent drug of this class. Other drugs belonging to this class include siponimod, ponesimod, ceralifimod, amiselimod, CS-0777 and GSK2018682. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28990207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "S1P receptor antagonists fingolimod and siponimod do not improve the outcome of experimental autoimmune myasthenia gravis mice after disease onset.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29205338", "endSection": "title" }, { "offsetInBeginSection": 339, "offsetInEndSection": 647, "text": "Functional sphingosine-1-phosphate (S1P) antagonists like fingolimod and siponimod (BAF312) are successfully used for the treatment of multiple sclerosis, and fingolimod was shown to prevent the development of myasthenic symptoms in experimental autoimmune myasthenia gravis (EAMG), the standard model of MG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29205338", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 648, "text": "Thus, the aim of this study was to characterize the immunomodulatory effect of the functional S1PR1 antagonist, siponimod, in phase III clinical trials for autoimmune disorders and of the competitive sphingosine 1-phosphate receptor subtype 1 (S1PR1) antagonist, TASP0277308, in pre-clinical development in an in vivo model of TBI in mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310513", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 679, "text": "In addition, there are three more specific S1P agonists in late stages of development: siponimod, ponesimod, and ozanimod.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29500302", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 307, "text": "We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor1,5 modulator, on disability progression in patients with SPMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29576505", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1155, "text": "Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29627873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "A high incidence of hemangiosarcoma (HSA) was observed in mice treated for 2\u00a0years with siponimod, a sphingosine-1-phosphate receptor 1 (S1P1) functional antagonist, while no such tumors were observed in rats under the same treatment conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29556671", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 597, "text": "Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27566665", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 604, "text": "BAF312 (siponimod) is a novel sphingosine-1-phosphate receptor modulator shown to delay progression in PMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31290453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "BACKGROUND\n\nSiponimod is an oral selective modulator of sphingosine 1-phosphate receptor types 1 and type 5, with an elimination half-life leading to washout in 7 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23764350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "The next-generation sphingosine-1 receptor modulator BAF312 (siponimod) improves cortical network functionality in focal autoimmune encephalomyelitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31290453", "endSection": "title" }, { "offsetInBeginSection": 375, "offsetInEndSection": 574, "text": "Siponimod is an S1PR (sphingosine-1-phosphate receptor) modulator, which blocks the egress of lymphocytes from lymphoid organs and has demonstrated beneficial effects in multiple sclerosis treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Siponimod, a next-generation selective sphingosine-1-phosphate receptor modulator, is currently being investigated for the treatment of secondary progressive multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29735753", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 518, "text": "Siponimod is a newer-generation sphingosine 1 phosphate (S1P) receptor modulator that internalizes S1P1 receptors, thereby inhibiting efflux of lymphocytes from lymph nodes and thymus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31603362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900670", "endSection": "title" }, { "offsetInBeginSection": 326, "offsetInEndSection": 512, "text": "Siponimod is a newer-generation sphingosine 1 phosphate ( S1P ) receptor modulator that internalizes S1P1 receptors , thereby inhibiting efflux of lymphocytes from lymph nodes and thymus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31603362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Siponimod ( Mayzent ) is an oral selective sphingosine 1-phosphate receptor subtypes 1 and 5 ( S1PR ) modulator being developed by Novartis Pharmaceuticals for the treatment of multiple sclerosis ( MS ) and intracerebral haemorrhage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31144287", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 358, "text": "Similar to fingolimod , siponimod is a sphingosine-1-phosphate receptor modulator that inhibits the egress of a lymphocyte subpopulation from lymph nodes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29110882", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 581, "text": "Siponimod is an S1PR ( sphingosine-1-phosphate receptor ) modulator , which blocks the egress of lymphocytes from lymphoid organs and has demonstrated beneficial effects in multiple sclerosis treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Discovery of BAF312 ( Siponimod) , a Potent and Selective S1P Receptor Modulator", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24900670", "endSection": "title" }, { "offsetInBeginSection": 739, "offsetInEndSection": 1165, "text": "Proof-of-concept studies across validated animal models with S1P receptor modulators highly selective for S1P1 , such as BAF-312 ( Siponimod) , KRP-203 , ONO-4641 ( Ceralifimod) , ponesimod and RPC-1063 , and emerging clinical trials for safety and efficacy in humans , particularly in MS , ulcerative colitis ( UC ) and psoriasis , have set the stage for us to consider additional testing in various other autoimmune diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25580263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "BAF312 ( siponimod ) is a sphingosine-1-phosphate ( S1P ) receptor modulator in clinical development for the treatment of multiple sclerosis , with faster organ/tissue distribution and elimination kinetics than its precursor FTY720 ( fingolimod", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25924727", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 648, "text": "Functional sphingosine-1-phosphate (S1P) antagonists like fingolimod and siponimod (BAF312) are successfully used for the treatment of multiple sclerosis, and fingolimod was shown to prevent the development of myasthenic symptoms in experimental autoimmune myasthenia gravis (EAMG), the standard model of MG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29205338", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 597, "text": "Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27566665", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 575, "text": "Siponimod is an S1PR (sphingosine-1-phosphate receptor) modulator, which blocks the egress of lymphocytes from lymphoid organs and has demonstrated beneficial effects in multiple sclerosis treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Siponimod (BAF312) is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P) modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29138536", "endSection": "abstract" }, { "offsetInBeginSection": 2619, "offsetInEndSection": 2798, "text": "INTERPRETATION: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29576505", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 636, "text": "Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing-remitting [RR] multiple sclerosis [MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29138536", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 652, "text": "In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25223691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "BAF312 (Siponimod) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26856814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "BAF312 (siponimod) is a sphingosine-1-phosphate (S1P) receptor modulator in clinical development for the treatment of multiple sclerosis, with faster organ/tissue distribution and elimination kinetics than its precursor FTY720 (fingolimod).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25924727", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 500, "text": "Siponimod, a selective modulator of sphingosine 1-phosphate receptors type 1 and type 5, demonstrated an excellent safety profile in a large study of patients with multiple sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31558140", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 585, "text": "Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27566665", "endSection": "abstract" } ] }, { "body": "What is a zoonotic virus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29495551", "http://www.ncbi.nlm.nih.gov/pubmed/29655214", "http://www.ncbi.nlm.nih.gov/pubmed/29563201", "http://www.ncbi.nlm.nih.gov/pubmed/28202592", "http://www.ncbi.nlm.nih.gov/pubmed/28192435", "http://www.ncbi.nlm.nih.gov/pubmed/29351657" ], "ideal_answer": [ "A zoonotic disease is a disease that can be passed from animals to humans. Zoonotic viruses may adapt to a human host eventually becoming endemic in humans, but before doing so punctuated outbreaks of the zoonotic virus may be observed." ], "type": "summary", "id": "5e5d2b4c1af46fc130000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Rift Valley fever virus (RVFV) is a mosquito-borne, zoonotic virus that infects ruminants, including cattle, sheep, goats, camels, and buffalo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29563201", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Hepatitis E virus (HEV) is a zoonotic virus which circulates in pigs and wild boars as main reservoir species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29655214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29495551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Nipah virus is a zoonotic virus harbored by bats and lethal to humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29351657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "A zoonotic disease is a disease that can be passed from animals to humans. Zoonotic viruses may adapt to a human host eventually becoming endemic in humans, but before doing so punctuated outbreaks of the zoonotic virus may be observed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28202592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Monkeypox virus (MPXV), a close relative of Variola virus, is a zoonotic virus with an unknown reservoir. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28192435", "endSection": "abstract" } ] }, { "body": "Which drug is the first oral ghrelin receptor inverse agonist to be profiled in healthy subjects?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27621150" ], "ideal_answer": [ "PF-05190457 is the first oral ghrelin receptor inverse agonist to be profiled in healthy subjects." ], "exact_answer": [ "PF-05190457" ], "type": "factoid", "id": "5e49ac346d0a27794100000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27621150", "endSection": "title" } ] }, { "body": "What is the function of BRD4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28837371", "http://www.ncbi.nlm.nih.gov/pubmed/21652721", "http://www.ncbi.nlm.nih.gov/pubmed/28933601", "http://www.ncbi.nlm.nih.gov/pubmed/25788266", "http://www.ncbi.nlm.nih.gov/pubmed/28525743", "http://www.ncbi.nlm.nih.gov/pubmed/17626100", "http://www.ncbi.nlm.nih.gov/pubmed/28174254", "http://www.ncbi.nlm.nih.gov/pubmed/25284786", "http://www.ncbi.nlm.nih.gov/pubmed/30483785" ], "ideal_answer": [ "As a member of the bromodomain and extraterminal (BET) family, BRD4 (bromodomain containing 4) can bind to acetylated histones and transcription factors, and is also able to recruit various transcriptional regulators. As transcriptional coactivator, BRD4 represses autophagy and lysosomal function.", "Our recent study revealed that autophagy programs are transcriptionally suppressed by the BET family protein BRD4." ], "type": "summary", "id": "5d35f07b7bc3fee31f000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Brd4-independent transcriptional repression function of the papillomavirus e2 proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17626100", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 374, "text": "the cellular bromodomain protein Brd4 as a major E2-interacting protein and established that it participates in tethering bovine papillomavirus type 1 E2 and viral genomes to host cell mitotic chromosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17626100", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 453, "text": "Brd4 mediates E2-dependent transcriptional activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17626100", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1312, "text": "Knockdown of BRD4-NUT in NMC cells disperses the transcriptionally inactive chromatin foci and releases the transcriptional activators to stimulate c-fos expression, leading to restoration of cellular differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21652721", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 707, "text": "Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25284786", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 824, "text": "BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individual", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25284786", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 475, "text": "n important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER+ breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25788266", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 344, "text": " Such mechanisms may also render leukemia cells vulnerable to perturbations of transcriptional regulators, which includes small molecules targeting the coactivator protein BRD4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28174254", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 457, "text": "Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28525743", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 379, "text": "Our recent study revealed that autophagy programs are transcriptionally suppressed by the BET family protein BRD4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28933601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "BRD4 is a newly characterized transcriptional regulator that represses autophagy and lysosomal function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28837371", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "As a member of the bromodomain and extraterminal (BET) family, BRD4 (bromodomain containing 4) can bind to acetylated histones and transcription factors, and is also able to recruit various transcriptional regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28837371", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1120, "text": "Taken together, the newly reported repressive role of BRD4 in autophagy adds to our understanding of how autophagy and lysosome functions are regulated at the transcriptional level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28837371", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 514, "text": "The olfactory bromodomain\u2011containing protein 4 (BRD4) is a protein that recognizes and binds acetylated lysine. It has been reported that the high expression of BRD4 is involved in the process of cardiac hypertrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30483785", "endSection": "abstract" } ] }, { "body": "What is the protective efficacy of vaxchora against moderate to severe cholera?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27425792" ], "ideal_answer": [ "The protective efficacy of vaxchora against moderate to severe cholera is 80-100%." ], "exact_answer": [ "80-100%" ], "type": "factoid", "id": "5e76452fc6a8763d23000015", "snippets": [ { "offsetInBeginSection": 255, "offsetInEndSection": 614, "text": "The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27425792", "endSection": "abstract" } ] }, { "body": "What is minodixil approved for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30155952" ], "ideal_answer": [ "Minoxidil is the only topical drug approved for the treatment of both female and male pattern hair loss. In the US, minoxidil is approved over-the-counter (OTC) at a maximum concentration of 5%." ], "type": "summary", "id": "5e499e0a6d0a27794100000b", "snippets": [ { "offsetInBeginSection": 175, "offsetInEndSection": 360, "text": "Minoxidil is the only topical drug for the treatment of both female and male pattern hair loss. In the US, minoxidil is approved over-the-counter (OTC) at a maximum concentration of 5%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30155952", "endSection": "abstract" } ] }, { "body": "Are Chernobyl survivors at increased risk for breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29787442", "http://www.ncbi.nlm.nih.gov/pubmed/20569256", "http://www.ncbi.nlm.nih.gov/pubmed/29531473", "http://www.ncbi.nlm.nih.gov/pubmed/19956182", "http://www.ncbi.nlm.nih.gov/pubmed/23691737", "http://www.ncbi.nlm.nih.gov/pubmed/26695891", "http://www.ncbi.nlm.nih.gov/pubmed/16506213", "http://www.ncbi.nlm.nih.gov/pubmed/28230825" ], "ideal_answer": [ "Yes, Chernobyl survivors are at increased risk for breast cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5e338cf5fbd6abf43b00005d", "snippets": [ { "offsetInBeginSection": 1079, "offsetInEndSection": 1240, "text": "Results: A more aggressive course of breast cancer is observed in patients exposed to radiation from the Chernobyl accident under the age of 30\u2009years (P\u2009<\u2009.01). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29531473", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1153, "text": "A significant excess of multiple myeloma incidence [standardized incidence rate (SIR) 1.61 %, 95% confidence interval (CI) 1.01-2.21], thyroid cancer (SIR 4.18, 95% CI 3.76-4.59), female breast cancer (SIR 1.57 CI 1.40-1.73), and all cancers combined (SIR 1.07; 95% CI 1.05-1.09) was registered. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29787442", "endSection": "abstract" }, { "offsetInBeginSection": 1594, "offsetInEndSection": 1875, "text": "Possible effects for further study include increased rates of thyroid, breast, and lung cancers and multiple myeloma; reduction of radiation risks of leukemia to population levels; and increased morbidity and mortality of cleanup workers from cardio- and cerebrovascular pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29787442", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 674, "text": "Furthermore, the upward trends of increases in a variety of other tumors including breast cancer, cancers of central nervous system and renal cancer have been reported in the persons exposed to Chornobyl fallout.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28230825", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 755, "text": "Epidemiological cohort studies found increased incidence (1990-2012 gg.) of thyroid cancer in victims of Chernobyl accident (liquidators - in 4.6 times, evacuated - in 4.0 times, residents of contaminated areas - in 1.3 times) and increased incidence of breast cancer in female workers of 1986-1987.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26695891", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 378, "text": "Historically, data from the Chernobyl reactor accident 27 years ago demonstrated a strong correlation with thyroid cancer, but data on the radiation effects of Chernobyl on breast cancer incidence have remained inconclusive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23691737", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 907, "text": "Re-analyzing the data reveals that the incidence of breast cancer in Chernobyl-disaster-exposed women could be higher than previously thought. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23691737", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 273, "text": "For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20569256", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 740, "text": "In contrast, millions of people were exposed to radioactive isotopes in the fallout from the Chernobyl accident, within the first 20 years there was a large increase in thyroid carcinoma incidence and a possible radiation-related increase in breast cancer, but as yet there is no general increase in malignancies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19956182", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1067, "text": "The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16506213", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "An increase in breast cancer incidence has been reported in areas of Belarus and Ukraine contaminated by the Chernobyl accident and has become an issue of public concern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16506213", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1068, "text": "The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16506213", "endSection": "abstract" } ] }, { "body": "What is AZD0530 an inhibitor of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22623106" ], "ideal_answer": [ "AZD0530 is a highly selective, dual Src/Abl kinase inhibitor." ], "exact_answer": [ "dual Src/Abl kinase" ], "type": "factoid", "id": "5e5409776d0a277941000051", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Saracatinib, a highly selective, dual Src/Abl kinase inhibitor, is currently in a Phase II clinical trial for the treatment of ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22623106", "endSection": "abstract" } ] }, { "body": "Is SATB1 necessary for T-cell maturation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17652321", "http://www.ncbi.nlm.nih.gov/pubmed/16371359", "http://www.ncbi.nlm.nih.gov/pubmed/15618465" ], "ideal_answer": [ "Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling.", "Yes. SATB1 is an essential factor for the regulation of T-cell maturation.", "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell.", "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. the transcription factor SATB1 that regulates the T-cell maturation SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell.", "Yes, SATB1 is necessary for T-cell maturation.", "Yes. SATB1 is an essential regulator of T-cell maturation.", "Yes, SATB1 is required for T-cell maturation.", "SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling.", "Yes. SATB1 is associated with the late-M-to-early-G1 phase of T-cell maturation and its activation correlates with histone H3 hyperacetylation, DNA methylation, and chromatin reorganization at the transcriptional level, while it is involved in the early stages of T cell differentiation into the erythroid lineage.", "yes, SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. ", "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation.", "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. the transcription factor SATB1 that regulates the T-cell maturation", "the transcription factor SATB1 that regulates the T-cell maturation. SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell.", "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling.", "the transcription factor SATB1 that regulates the T-cell maturation Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling." ], "exact_answer": "yes", "type": "yesno", "id": "5d36b4817bc3fee31f000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15618465", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 157, "text": "the transcription factor SATB1 that regulates the T-cell maturation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16371359", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16371359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17652321", "endSection": "abstract" } ] }, { "body": "For how long do Drosophila embryos use maternal genome mRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29601592", "http://www.ncbi.nlm.nih.gov/pubmed/17448252", "http://www.ncbi.nlm.nih.gov/pubmed/2702688" ], "ideal_answer": [ "mitoses before interphase 14 run on maternal products and occur in metasynchronous waves", "before interphase 14", "Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves. In many animals, the first few hours of life proceed with little or no transcription, and developmental regulation at these early stages is dependent on maternal cytoplasm rather than the zygotic nucleus.", "Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves.", "In Drosophila embryogenesis mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves.", "Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves. An exceptional case of Nos-independent regulation by Pum has been described-repression of maternal bicoid (bcd) m RNA at the anterior pole of the early embryo, dependent on both Pum and conserved Pum binding sites in the 3'- UTR of the m RNA" ], "exact_answer": [ "14 cell divisions" ], "type": "factoid", "id": "5d35e421b3a638076300000d", "snippets": [ { "offsetInBeginSection": 108, "offsetInEndSection": 198, "text": "Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2702688", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 216, "text": "In many animals, the first few hours of life proceed with little or no transcription, and developmental regulation at these early stages is dependent on maternal cytoplasm rather than the zygotic nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17448252", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 951, "text": ". An exceptional case of Nos-independent regulation by Pum has been described-repression of maternal bicoid (bcd) mRNA at the anterior pole of the early embryo, dependent on both Pum and conserved Pum binding sites in the 3'-UTR of the mRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29601592", "endSection": "abstract" } ] }, { "body": "What is the use of erenumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29616494", "http://www.ncbi.nlm.nih.gov/pubmed/31612482", "http://www.ncbi.nlm.nih.gov/pubmed/31284729", "http://www.ncbi.nlm.nih.gov/pubmed/31302899", "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "http://www.ncbi.nlm.nih.gov/pubmed/30276500", "http://www.ncbi.nlm.nih.gov/pubmed/30963506", "http://www.ncbi.nlm.nih.gov/pubmed/30793254", "http://www.ncbi.nlm.nih.gov/pubmed/30235976", "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "http://www.ncbi.nlm.nih.gov/pubmed/29571276", "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "http://www.ncbi.nlm.nih.gov/pubmed/29406534", "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "http://www.ncbi.nlm.nih.gov/pubmed/29263689", "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "http://www.ncbi.nlm.nih.gov/pubmed/30813769", "http://www.ncbi.nlm.nih.gov/pubmed/30142988", "http://www.ncbi.nlm.nih.gov/pubmed/30614741" ], "ideal_answer": [ "Erenumab is a fully human monoclonal antibody calcitonin gene-related peptide (CGRP) receptor antagonist-for the prevention of migraine. CGRP is a vasodilatory neuropeptide implicated in the pathophysiology of migraine and treatment with erenumab was associated with significant reductions in migraine frequency in phase II and III clinical trials. Based on these positive results erenumab was recently approved in the US for the preventive treatment of migraine in adults and has received a positive opinion in the EU for the prophylaxis of migraines in adults who have at least 4 migraine days per month.\n\nConclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use." ], "type": "summary", "id": "5e48b7e2d14c9f295d000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "endSection": "title" }, { "offsetInBeginSection": 821, "offsetInEndSection": 971, "text": "Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29432219", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 238, "text": "Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "endSection": "abstract" }, { "offsetInBeginSection": 1811, "offsetInEndSection": 1994, "text": "Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70\u2009mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "endSection": "abstract" }, { "offsetInBeginSection": 522, "offsetInEndSection": 778, "text": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Estimating the clinical effectiveness and value-based price range of erenumab for the prevention of migraine in patients with prior treatment failures: a US societal perspective.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571276", "endSection": "title" }, { "offsetInBeginSection": 1915, "offsetInEndSection": 2037, "text": "CONCLUSION: Erenumab is predicted to reduce migraine-related direct and indirect costs, and increase QALYs compared to SC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571276", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 360, "text": "Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29616494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 664, "text": "Amgen and Novartis are developing erenumab (AIMOVIG\u2122, erenumab-aooe)-a fully human monoclonal antibody calcitonin gene-related peptide (CGRP) receptor antagonist-for the prevention of migraine. CGRP is a vasodilatory neuropeptide implicated in the pathophysiology of migraine and treatment with erenumab was associated with significant reductions in migraine frequency in phase II and III clinical trials. Based on these positive results erenumab was recently approved in the US for the preventive treatment of migraine in adults and has received a positive opinion in the EU for the prophylaxis of migraines in adults who have at least 4 migraine days per month. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 372, "text": "Erenumab is a new preventive treatment for migraines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31302899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Erenumab: A First-in-Class Monoclonal Antibody for Migraine Prevention.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30813769", "endSection": "title" }, { "offsetInBeginSection": 285, "offsetInEndSection": 412, "text": "Erenumab is the first fully human monoclonal antibody directed against the CGRP receptor to be approved for use in migraineurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30793254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Erenumab for episodic migraine prophylaxis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30614741", "endSection": "title" }, { "offsetInBeginSection": 131, "offsetInEndSection": 262, "text": "Erenumab is a fully human monoclonal antibody (mAb), which specifically blocks the calcitonin gene-related peptide (GGRP) receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30614741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Cost-Effectiveness Analysis of Erenumab Versus OnabotulinumtoxinA for Patients with Chronic Migraine Attacks in Greece.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31302899", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "A Controlled Trial of Erenumab for Episodic Migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "title" }, { "offsetInBeginSection": 1582, "offsetInEndSection": 1720, "text": "Conclusion: Erenumab is an effective once-monthly injectable agent for migraine prevention in patients with chronic or episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30813769", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 212, "text": "Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "endSection": "abstract" }, { "offsetInBeginSection": 1683, "offsetInEndSection": 2043, "text": "Conclusion The use of erenumab may be a cost-effective approach to preventing monthly migraine days among patients with chronic migraine versus onabotulinumtoxinA and no preventive treatment in the societal and payer perspectives, but is less likely to offer good value for money for those with episodic migraine, unless lost productivity costs are considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142988", "endSection": "abstract" }, { "offsetInBeginSection": 2306, "offsetInEndSection": 2557, "text": "CONCLUSIONS\n\nErenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" }, { "offsetInBeginSection": 1615, "offsetInEndSection": 1748, "text": "CONCLUSIONS\n\nErenumab is an efficacious and well tolerated preventive treatment in adult patients with episodic and chronic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30793254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Cost-effectiveness analysis of erenumab for the preventive treatment of episodic and chronic migraine: Results from the US societal and payer perspectives.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142988", "endSection": "title" }, { "offsetInBeginSection": 318, "offsetInEndSection": 371, "text": "Erenumab is a new preventive treatment for migraines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31302899", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 211, "text": "Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Erenumab in the treatment of migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30235976", "endSection": "title" }, { "offsetInBeginSection": 1704, "offsetInEndSection": 2065, "text": "Conclusion The use of erenumab may be a cost-effective approach to preventing monthly migraine days among patients with chronic migraine versus onabotulinumtoxinA and no preventive treatment in the societal and payer perspectives , but is less likely to offer good value for money for those with episodic migraine , unless lost productivity costs are considered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29263689", "endSection": "title" }, { "offsetInBeginSection": 411, "offsetInEndSection": 667, "text": "Based on these positive results erenumab was recently approved in the US for the preventive treatment of migraine in adults and has received a positive opinion in the EU for the prophylaxis of migraines in adults who have at least 4 migraine days per month", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Erratum: Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab [ Corrigendum", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29406534", "endSection": "title" }, { "offsetInBeginSection": 96, "offsetInEndSection": 238, "text": "Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 372, "text": "Erenumab is a new preventive treatment for migraines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31302899", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 412, "text": "Erenumab is the first fully human monoclonal antibody directed against the CGRP receptor to be approved for use in migraineurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30793254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Erenumab for Preventive Treatment of Migraine: A Systematic Review and Meta-Analysis of Efficacy and Safety.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30793254", "endSection": "title" }, { "offsetInBeginSection": 414, "offsetInEndSection": 556, "text": "OBJECTIVE\nTo evaluate the efficacy and safety of erenumab as preventive treatment in patients with migraine using meta-analytical techniques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30793254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29263689", "endSection": "title" }, { "offsetInBeginSection": 1683, "offsetInEndSection": 2044, "text": "Conclusion The use of erenumab may be a cost-effective approach to preventing monthly migraine days among patients with chronic migraine versus onabotulinumtoxinA and no preventive treatment in the societal and payer perspectives, but is less likely to offer good value for money for those with episodic migraine, unless lost productivity costs are considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "BACKGROUND: Erenumab is a human anti-calcitonin gene-related peptide monoclonal antibody developed for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30963506", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 237, "text": "Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29471679", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 405, "text": "CGRP is a vasodilatory neuropeptide implicated in the pathophysiology of migraine and treatment with erenumab was associated with significant reductions in migraine frequency in phase II and III clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "endSection": "abstract" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1253, "text": "Results With an annual drug price of erenumab of $6900, treatment with erenumab in the societal perspective ranges from a dominant strategy versus no preventive treatment among chronic migraine patients to an incremental cost-effectiveness ratio of $122,167 versus no preventive treatment among episodic migraine patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30142988", "endSection": "abstract" }, { "offsetInBeginSection": 1217, "offsetInEndSection": 1469, "text": "CONCLUSION: Monthly subcutaneous injections of erenumab 70\u00a0mg demonstrated statistically significant and numerically maximal efficacy with a favorable safety profile, suggesting that erenumab is a potential new therapy for migraine prevention in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31612482", "endSection": "abstract" }, { "offsetInBeginSection": 1273, "offsetInEndSection": 1525, "text": "PCONCLUSIONS: Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 407, "text": "Erenumab is a human CGRP-receptor antibody approved for the prophylactic treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31284729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "BACKGROUND: We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Early onset of efficacy with erenumab in patients with episodic and chronic migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30276500", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "BACKGROUND: Subcutaneous erenumab reduced monthly migraine days and increased the likelihood of achieving a\u2009\u2265\u200950% reduction at all monthly assessment points tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30276500", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 360, "text": "Erenumab is a new preventive treatment for migraines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31302899", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 576, "text": "To evaluate the differences in costs and outcomes of the preventive treatment with erenumab versus onabotulinumtoxinA in patients with chronic migraines (CM) in Greece to assess the economic value of this treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31302899", "endSection": "abstract" }, { "offsetInBeginSection": 2273, "offsetInEndSection": 2511, "text": "Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1657, "text": "Conclusion: Erenumab is an effective once-monthly injectable agent for migraine prevention in patients with chronic or episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30813769", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 400, "text": "Erenumab is the first fully human monoclonal antibody directed against the CGRP receptor to be approved for use in migraineurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30793254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Erenumab is a human anti-calcitonin gene-related peptide monoclonal antibody developed for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30963506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171821", "endSection": "abstract" } ] }, { "body": "What is the function of a viral peplomer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7679743", "http://www.ncbi.nlm.nih.gov/pubmed/9782260", "http://www.ncbi.nlm.nih.gov/pubmed/1402806", "http://www.ncbi.nlm.nih.gov/pubmed/1658026" ], "ideal_answer": [ "The coronavirus peplomer protein S is responsible for attachment and fusion during viral entry as well as for the induction of cell to cell fusion.\nSince tissue affinities are a function of the viral peplomer-mediated attachment of virus to cells and are often directly related to pathogenicity," ], "exact_answer": [ "attachment and fusion during viral entry as well as for the induction of cell to cell fusion." ], "type": "factoid", "id": "5e5bafa01af46fc130000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The coronavirus peplomer protein S is responsible for attachment and fusion during viral entry as well as for the induction of cell to cell fusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9782260", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1050, "text": "Since tissue affinities are a function of the viral peplomer-mediated attachment of virus to cells and are often directly related to pathogenicity,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1658026", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1627, "text": "Thus, inhibition of the N-glycosylation of the S and HE structural proteins prevented their incorporation into progeny virions, an indication that they are dispensable for virion morphogenesis, unlike the M protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1402806", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Numerous studies have demonstrated that the spike glycoprotein of coronaviruses bears major determinants of pathogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7679743", "endSection": "abstract" } ] }, { "body": "Have toll-like receptor 2 activators been found in food?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26242919" ], "ideal_answer": [ "Yes, toll-like receptor 2 activators (TLR2) have been found in food.", "Yes, Toll-like receptor 2 activators (TLR2) have been found in food.", "Yes, Toll-like receptor 2 (TLR2) activators have been found in food.", "toll-like receptor 2 (tlr2) ) is a widely expressed pattern recognition receptor critical for innate immunity. tlr2 activators are found in many common foods", "Yes, Toll-like receptor 2 activators have been found in food.", "Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease and they are found in many common foods. ", "Toll-like receptor 2 ( TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods,", "yes, Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods,", "Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods,", "TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods," ], "exact_answer": "yes", "type": "yesno", "id": "5e46bf743f54159529000008", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 268, "text": "Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26242919", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 367, "text": "TLR2 activators are found in many common foods, but the role of TLR2 in oral tolerance and allergic sensitization to foods is not well understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26242919", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 367, "text": "TLR2 activators are found in many common foods, but the role of TLR2 in oral tolerance and allergic sensitization to foods is not well understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26242919", "endSection": "abstract" } ] }, { "body": "Describe the Open Targets platform", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28587637", "http://www.ncbi.nlm.nih.gov/pubmed/27899665", "http://www.ncbi.nlm.nih.gov/pubmed/30462303", "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "http://www.ncbi.nlm.nih.gov/pubmed/28919242" ], "ideal_answer": [ "The Open Targets platform is a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org." ], "type": "summary", "id": "5e3714a8b5b409ea53000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Open Targets: a platform for therapeutic target identification and validation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899665", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 779, "text": "We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27899665", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 610, "text": "Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The recently developed Open Targets platform consolidates a wide range of comprehensive evidence associating known and potential drug targets with human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28919242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 600, "text": "Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The recently developed Open Targets platform consolidates a wide range of comprehensive evidence associating known and potential drug targets with human diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28919242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "The Open Targets Platform integrates evidence from genetics , genomics , transcriptomics , drugs , animal models and scientific literature to score and rank target-disease associations for drug target identification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30462303", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1465, "text": "Here, we present the latest developments of the Open Targets Platform, expanding the evidence and target-disease associations with new and improved data sources, refining data quality, enhancing website usability, and increasing our user base with our training workshops, user support, social media and bioinformatics forum engagement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30462303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "The Open Targets Platform integrates evidence from genetics, genomics, transcriptomics, drugs, animal models and scientific literature to score and rank target-disease associations for drug target identification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30462303", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 610, "text": "Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1626, "text": "CONCLUSIONS\nThe Open Targets gene-disease score can be used to prioritize potential G-protein coupled receptors-indication hypotheses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "BACKGROUND: The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1464, "text": "Here, we present the latest developments of the Open Targets Platform, expanding the evidence and target-disease associations with new and improved data sources, refining data quality, enhancing website usability, and increasing our user base with our training workshops, user support, social media and bioinformatics forum engagement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30462303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The Open Targets Platform integrates evidence from genetics, genomics, transcriptomics, drugs, animal models and scientific literature to score and rank target-disease associations for drug target identification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30462303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 404, "offsetInEndSection": 598, "text": "Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28587637", "endSection": "abstract" } ] }, { "body": "Does radiotherapy for Hodgkin disease increases risk for lung cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11830608", "http://www.ncbi.nlm.nih.gov/pubmed/2754447", "http://www.ncbi.nlm.nih.gov/pubmed/11045784", "http://www.ncbi.nlm.nih.gov/pubmed/23053567", "http://www.ncbi.nlm.nih.gov/pubmed/27913498", "http://www.ncbi.nlm.nih.gov/pubmed/25104066", "http://www.ncbi.nlm.nih.gov/pubmed/25025999", "http://www.ncbi.nlm.nih.gov/pubmed/7563187", "http://www.ncbi.nlm.nih.gov/pubmed/2981984", "http://www.ncbi.nlm.nih.gov/pubmed/25615851", "http://www.ncbi.nlm.nih.gov/pubmed/1428226", "http://www.ncbi.nlm.nih.gov/pubmed/25754634", "http://www.ncbi.nlm.nih.gov/pubmed/26530956" ], "ideal_answer": [ "Yes, radiotherapy for Hodgkin disease is associated with increased risk for lung cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5e33904afbd6abf43b00005f", "snippets": [ { "offsetInBeginSection": 871, "offsetInEndSection": 965, "text": "Risks of lung, breast, and gastrointestinal (GI) cancers increase with higher radiation dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27913498", "endSection": "abstract" }, { "offsetInBeginSection": 1133, "offsetInEndSection": 1513, "text": "CONCLUSIONS: RT treatment, especially with doses higher than 42 Gy, and smoking increase the risk of SN after HL. In this series, LC patients with early stages had a shorter elapsed time from HL diagnosis and longer OS, therefore the role of LC screening in HL survivors should be prospectively evaluated and smoking cessation counseling ought to be a key aspect during follow-up.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26530956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Long-term Hodgkin lymphoma (HL) survivors have an increased risk of late cardiac morbidity and secondary lung cancer after chemotherapy and mediastinal radiotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25025999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "PURPOSE: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25754634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Lung cancer (LC) represents the most common solid tumor in survivors of Hodgkin's disease (HD), and the assessment of the mutational status of oncogenic driver mutations in LC is now standard. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25615851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "PURPOSE: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25104066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Increased risk of second lung cancer in Hodgkin's lymphoma survivors: a meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053567", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: Patients treated for Hodgkin's lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053567", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 939, "text": "The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18-6.70], I (2) = 98 %), with a median absolute excess rate of 10.4 per 10,000 person-years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053567", "endSection": "abstract" }, { "offsetInBeginSection": 1762, "offsetInEndSection": 1869, "text": "CONCLUSIONS: The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23053567", "endSection": "abstract" }, { "offsetInBeginSection": 2195, "offsetInEndSection": 2370, "text": "CONCLUSIONS\n\nThe excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7563187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND\n\nLung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11830608", "endSection": "abstract" }, { "offsetInBeginSection": 1807, "offsetInEndSection": 1998, "text": "CONCLUSIONS\n\nPast treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11830608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "BACKGROUND\n\nSeveral studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7563187", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 356, "text": "PURPOSE\n\nThis study was undertaken to investigate the effects of radiation dose, chemotherapy, and smoking on the risk of lung cancer following treatment of Hodgkin's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7563187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2754447", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1428226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "The risk of lung and breast cancer is significantly increased after therapy for Hodgkin 's disease ( HD) , but there are few data that describe the molecular profiles of these tumors . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11045784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Hodgkin lymphoma ( HL ) survivors have an increased risk of cardiovascular disease ( CD) , lung cancer , and breast cancer . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25754634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND\nLung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11830608", "endSection": "abstract" }, { "offsetInBeginSection": 1807, "offsetInEndSection": 1998, "text": "CONCLUSIONS\nPast treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11830608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Lung cancer in Hodgkin's disease: association with previous radiotherapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2981984", "endSection": "title" }, { "offsetInBeginSection": 651, "offsetInEndSection": 788, "text": "Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2981984", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 216, "text": "The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2981984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2981984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "BACKGROUND\nSeveral studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7563187", "endSection": "abstract" }, { "offsetInBeginSection": 2152, "offsetInEndSection": 2314, "text": "The excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7563187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11830608", "endSection": "abstract" }, { "offsetInBeginSection": 1774, "offsetInEndSection": 1952, "text": "Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11830608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Several studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7563187", "endSection": "abstract" } ] }, { "body": "Does radiotherapy for prostate cancer increase bladder cancer risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28499661", "http://www.ncbi.nlm.nih.gov/pubmed/27432454", "http://www.ncbi.nlm.nih.gov/pubmed/19553822", "http://www.ncbi.nlm.nih.gov/pubmed/25900243", "http://www.ncbi.nlm.nih.gov/pubmed/27844130", "http://www.ncbi.nlm.nih.gov/pubmed/27370205", "http://www.ncbi.nlm.nih.gov/pubmed/26936410", "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "http://www.ncbi.nlm.nih.gov/pubmed/27629559", "http://www.ncbi.nlm.nih.gov/pubmed/30293908" ], "ideal_answer": [ "Yes, radiotherapy for prostate cancer is associated with increased bladder cancer risk." ], "exact_answer": "yes", "type": "yesno", "id": "5e33916afbd6abf43b000061", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908", "endSection": "title" }, { "offsetInBeginSection": 1817, "offsetInEndSection": 2035, "text": "On multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18-1.55; p<0.001), but not RCa (p=0.4). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908", "endSection": "abstract" }, { "offsetInBeginSection": 2180, "offsetInEndSection": 2456, "text": "CONCLUSIONS: Patients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908", "endSection": "abstract" }, { "offsetInBeginSection": 2777, "offsetInEndSection": 2914, "text": "We found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30293908", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 1018, "text": "All radiation modalities were found to have an increased RR of developing BlCa after 10\u00a0years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27629559", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1427, "text": "CONCLUSIONS: The increased risk of BlCa after prostate radiation occurs predominantly after 10\u00a0years, regardless of ethnicity. The RR of developing BlCa after 10\u00a0years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27629559", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 716, "text": "Based on the data in the literature, there is a\u00a0consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27844130", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 956, "text": "When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28499661", "endSection": "abstract" }, { "offsetInBeginSection": 1637, "offsetInEndSection": 1734, "text": "LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27370205", "endSection": "abstract" }, { "offsetInBeginSection": 1807, "offsetInEndSection": 1914, "text": "Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27370205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "OBJECTIVE: Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 978, "text": "RESULTS: During the median follow-up period of 4.3 and 3.1 years, secondary bladder cancer occurred in 11 (3.4%) and 5 (1.1%) of patients with prostate cancer treated with external beam radiotherapy and radical prostatectomy, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1951, "text": "CONCLUSIONS\n\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "title" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1035, "text": "RESULTS\n\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1308, "text": "Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "OBJECTIVE\n\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "OBJECTIVE\nAlthough it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454", "endSection": "abstract" }, { "offsetInBeginSection": 1745, "offsetInEndSection": 1951, "text": "CONCLUSIONS\nMen who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "PURPOSE\nPre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 1035, "text": "RESULTS\nThe relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1835, "text": "CONCLUSIONS: Taken together, these findings suggest that smoking history might be one of criteria to choose radical prostatectomy than external beam radiotherapy for prostate cancer, and that age would not be a criterion for therapeutic selection in terms of secondary bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27432454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "PURPOSE: Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1031, "text": "RESULTS: The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1304, "text": "Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1894, "text": "Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 780, "offsetInEndSection": 992, "text": "The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18801517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Radiotherapy for prostate cancer is associated with an increased incidence of secondary bladder cancer (BC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25900243", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 977, "text": "Radiation therapy for prostate cancer is associated with an increased risk of bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19553822", "endSection": "abstract" }, { "offsetInBeginSection": 2204, "offsetInEndSection": 2429, "text": "Radiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26936410", "endSection": "abstract" } ] }, { "body": "What is ESN364?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26305889", "http://www.ncbi.nlm.nih.gov/pubmed/26653113" ], "ideal_answer": [ "systemic administration of an NK3R antagonist (ESN364) prolongs the LH interpulse interval in ovarectomized ewes and significantly lowers plasma LH and FSH concentrations in castrated nonhuman primates (Macaca fascicularis). Moreover, daily oral dosing of ESN364 throughout the menstrual cycle in M fascicularis lowered plasma estradiol levels in a dose-dependent manner, although nadir levels of estradiol were maintained well above menopausal levels. Nevertheless, estradiol levels during the follicular phase were sufficiently inhibited at all doses to preclude the triggering of ovulation as evidenced by the absence of the LH surge and failure of a subsequent luteal phase rise in plasma progesterone concentrations, consistent with the absence of normal cycle changes in the uterus. Apart from the point at surge, FSH levels were not altered over the course of the menstrual cycle. These effects of ESN364 were reversible upon cessation of drug treatment.\n\nESN364 was well-tolerated and rapidly bioavailable with linear pharmacokinetics and no drug accumulation with repeated, daily oral administration. Drug treatment dose-dependently decreased basal LH, but not FSH, and consequently decreased estradiol and progesterone (in women) as well as testosterone (in men). The hormonal changes in women corresponded to delayed ovulation, decreased endometrial thickening, impeded follicular maturation, and prolongation of the menstrual cycle. Drug effects were rapidly reversible. Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women. These results suggest that ESN364 may offer therapeutic benefit in the treatment of women's health disorders with a mitigated risk of menopausal-like adverse events." ], "type": "summary", "id": "5e550758b761aafe09000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The NK3 Receptor Antagonist ESN364 Interrupts Pulsatile LH Secretion and Moderates Levels of Ovarian Hormones Throughout the Menstrual Cycle.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305889", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 1286, "text": "In this report, we demonstrate that systemic administration of an NK3R antagonist (ESN364) prolongs the LH interpulse interval in ovarectomized ewes and significantly lowers plasma LH and FSH concentrations in castrated nonhuman primates (Macaca fascicularis). Moreover, daily oral dosing of ESN364 throughout the menstrual cycle in M fascicularis lowered plasma estradiol levels in a dose-dependent manner, although nadir levels of estradiol were maintained well above menopausal levels. Nevertheless, estradiol levels during the follicular phase were sufficiently inhibited at all doses to preclude the triggering of ovulation as evidenced by the absence of the LH surge and failure of a subsequent luteal phase rise in plasma progesterone concentrations, consistent with the absence of normal cycle changes in the uterus. Apart from the point at surge, FSH levels were not altered over the course of the menstrual cycle. These effects of ESN364 were reversible upon cessation of drug treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The NK3 Receptor Antagonist ESN364 Suppresses Sex Hormones in Men and Women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653113", "endSection": "title" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1785, "text": "ESN364 was well-tolerated and rapidly bioavailable with linear pharmacokinetics and no drug accumulation with repeated, daily oral administration. Drug treatment dose-dependently decreased basal LH, but not FSH, and consequently decreased estradiol and progesterone (in women) as well as testosterone (in men). The hormonal changes in women corresponded to delayed ovulation, decreased endometrial thickening, impeded follicular maturation, and prolongation of the menstrual cycle. Drug effects were rapidly reversible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653113", "endSection": "abstract" }, { "offsetInBeginSection": 1797, "offsetInEndSection": 2208, "text": " Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women. These results suggest that ESN364 may offer therapeutic benefit in the treatment of women's health disorders with a mitigated risk of menopausal-like adverse events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653113", "endSection": "abstract" } ] }, { "body": "Do genes with monoallelic expression contribute proportionally to genetic diversity in humans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26808112" ], "ideal_answer": [ "No, genes with monoallelic expression contribute disproportionately to genetic diversity in humans.", "No. Genes with monoallelic expression contribute disproportionately to genetic diversity in humans." ], "exact_answer": "no", "type": "yesno", "id": "5e51a2d76d0a27794100003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Genes with monoallelic expression contribute disproportionately to genetic diversity in humans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26808112", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1097, "text": "An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes uncovers surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit an elevated recombination rate and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: variants in these genes tend to be older and are enriched in polymorphisms shared by Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles of MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26808112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Genes with monoallelic expression contribute disproportionately to genetic diversity in humans", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26808112", "endSection": "title" } ] }, { "body": "Has MLE4901 been tested in phase III clinical trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28385352" ], "ideal_answer": [ "No, MLE4901 has been tested in phase 2, randomised, double-blind, placebo-controlled trial." ], "exact_answer": "no", "type": "yesno", "id": "5e5437ffb761aafe09000002", "snippets": [ { "offsetInBeginSection": 326, "offsetInEndSection": 533, "text": "METHODS\n\nThis phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28385352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28385352", "endSection": "title" } ] }, { "body": "Does ESN364 activate the hypothalamic-pituitary-gonadal axis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26653113" ], "ideal_answer": [ "No, the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion" ], "exact_answer": "no", "type": "yesno", "id": "5e5508e2b761aafe09000006", "snippets": [ { "offsetInBeginSection": 1798, "offsetInEndSection": 2042, "text": "Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26653113", "endSection": "abstract" } ] }, { "body": "Which type of variants can be called by the VarDict algorithm?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27060149" ], "ideal_answer": [ "VarDict is a novel and versatile variant caller for both DNA- and RNA-sequencing data. It simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation.", "VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood.", "VarDict is a novel and versatile variant caller for both DNA- and RNA-sequencing data. It calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors.", "VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors." ], "exact_answer": [ [ "SNV" ], [ "MNV" ], [ "InDels" ], [ "complex variants" ], [ "structural variants" ] ], "type": "list", "id": "5e2f6353fbd6abf43b00002b", "snippets": [ { "offsetInBeginSection": 110, "offsetInEndSection": 600, "text": "Here we present VarDict, a novel and versatile variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27060149", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 349, "text": "VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27060149", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 350, "text": "VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27060149", "endSection": "abstract" } ] }, { "body": "Has ORMD-0801 been tested in patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23593142" ], "ideal_answer": [ "Yes, ORMD-0801 has been tested in patients." ], "exact_answer": "yes", "type": "yesno", "id": "5e763645c6a8763d2300000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Glucose-reducing effect of the ORMD-0801 oral insulin preparation in patients with uncontrolled type 1 diabetes: a pilot study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593142", "endSection": "title" }, { "offsetInBeginSection": 393, "offsetInEndSection": 606, "text": "In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin) in addressing this resistant clinical state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23593142", "endSection": "abstract" } ] }, { "body": "Was vivotif licensed in Europe and the US at the same time?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28515625" ], "ideal_answer": [ "No, vivotif was licensed in Europe in 1983 and in the US in 1989." ], "exact_answer": "no", "type": "yesno", "id": "5e763c3fc6a8763d23000010", "snippets": [ { "offsetInBeginSection": 798, "offsetInEndSection": 1060, "text": "Vivotif\u00ae is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28515625", "endSection": "abstract" } ] }, { "body": "Are stem cell transplants used to treat acute kidney injury?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25640064", "http://www.ncbi.nlm.nih.gov/pubmed/22892486", "http://www.ncbi.nlm.nih.gov/pubmed/28411358" ], "ideal_answer": [ "Yes, stem cell transplantation is becoming the treatment of choice for complicated acute kidney injury.", "Yes, stem cell transplantation is being used for treatment of acute kidney injury.", "Yes, stem cell transplants are being used for treatment of acute kidney injury.", "Yes, stem cell transplants are being used for acute kidney injury treatment.", "Yes, stem cell transplants are being used to treat acute kidney injury.", "Yes, Animal studies have shown that mesenchymal stromal cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24 hours after cisplatin administration.", "D" ], "exact_answer": "yes", "type": "yesno", "id": "5e43090d48dab47f26000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Animal studies have shown that mesenchymal stromal cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24 hours after cisplatin administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25640064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28411358", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Risk assessment for acute kidney injury after allogeneic hematopoietic stem cell transplantation based on Acute Kidney Injury Network criteria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892486", "endSection": "title" } ] }, { "body": "What is the interaction between WAPL and PDS5 proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20696838", "http://www.ncbi.nlm.nih.gov/pubmed/29447171", "http://www.ncbi.nlm.nih.gov/pubmed/27872142", "http://www.ncbi.nlm.nih.gov/pubmed/29217591", "http://www.ncbi.nlm.nih.gov/pubmed/28220956", "http://www.ncbi.nlm.nih.gov/pubmed/19696148" ], "ideal_answer": [ "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. ", "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin.", "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes.", "Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head. Pds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction.", "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head", "we propose that wapl and pds5 directly modulate conformational changes of cohesin to make it competent for dissolving from chromatin during prophase", "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin", "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction.", "Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin ", "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head", " the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction.", "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction." ], "type": "summary", "id": "5d35c070b3a6380763000006", "snippets": [ { "offsetInBeginSection": 996, "offsetInEndSection": 1148, "text": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19696148", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1327, "text": "Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20696838", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 587, "text": "Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27872142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27872142", "endSection": "title" }, { "offsetInBeginSection": 529, "offsetInEndSection": 622, "text": " the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217591", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 266, "text": "the cohesin regulators Pds5 and Wapl release cohesin from chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28220956", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 562, "text": "a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28220956", "endSection": "abstract" }, { "offsetInBeginSection": 582, "offsetInEndSection": 718, "text": "Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28220956", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1403, "text": "ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29447171", "endSection": "abstract" } ] }, { "body": "Is deletion at 6q24.2-26 associated with shorter survival for ovarian cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "http://www.ncbi.nlm.nih.gov/pubmed/26463438" ], "ideal_answer": [ "No, the 6q24.2-26 deletion is an independent marker of favorable outcome in high-grade serous ovarian carcinoma (HGSOC) patients with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.", "No, deletion at 6q24.2-26 predicts longer survival of high-grade serous ovarian cancer patients." ], "exact_answer": "no", "type": "yesno", "id": "5e51dab06d0a27794100003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1882, "text": "Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evaluate the utility of DNA copy number alterations, as potential predictors of clinical outcome. Copy number-based unsupervised clustering stratified HGSOCs into two clusters of different immunohistopathological features and survival outcome (HR = 0.15, 95%CI = 0.03-0.81; Padj = 0.03). We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 789, "text": "We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "OBJECTIVE\n\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 790, "text": "We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25454820", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "OBJECTIVE\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463438", "endSection": "abstract" } ] }, { "body": "What is the function of a protein kinase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29187526", "http://www.ncbi.nlm.nih.gov/pubmed/29157894", "http://www.ncbi.nlm.nih.gov/pubmed/29724125", "http://www.ncbi.nlm.nih.gov/pubmed/28918129", "http://www.ncbi.nlm.nih.gov/pubmed/26745528", "http://www.ncbi.nlm.nih.gov/pubmed/29175418" ], "ideal_answer": [ "Protein kinases are enzymes that add a phosphate (PO4) group to a protein, and can modulate its function." ], "type": "summary", "id": "5e4f2aeb6d0a277941000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Mycobacterial protein tyrosine kinase, PtkA phosphorylates PtpA at tyrosine residues and the mechanism is stalled by the novel series of inhibitors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29724125", "endSection": "title" }, { "offsetInBeginSection": 341, "offsetInEndSection": 484, "text": "Tyrosine kinase (PtkA;TK) activated by autophosphorylation; phosphorylates TP, which subsequently leads to increase in its phosphatase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29724125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28918129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Src family kinase tyrosine phosphorylates Toll-like receptor 4 to dissociate MyD88 and Mal/Tirap, suppressing LPS-induced inflammatory responses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29175418", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Several studies have revealed that cyclin-dependent kinases (CDK) can mediate phosphorylation of steroid receptors at multiple sites, including serine 81 of the androgen receptor (AR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Selective inhibition reveals cyclin-dependent kinase 2 as another kinase that phosphorylates the androgen receptor at serine 81.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157894", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Aurora A kinase phosphorylates Hec1 to regulate metaphase kinetochore-microtubule dynamics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29187526", "endSection": "title" }, { "offsetInBeginSection": 110, "offsetInEndSection": 233, "text": "Central to this regulation is Aurora B kinase, which phosphorylates kinetochore substrates to promote microtubule turnover.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29187526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Protein kinases are known primarily for their ability to phosphorylate protein substrates, which constitutes an essential biological process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26745528", "endSection": "abstract" } ] }, { "body": "Which was the first cholera vaccine approved in the US?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29018300" ], "ideal_answer": [ "Vaxchora is the first vaccine approved by the Food and Drug Administration for the prophylaxis of cholera infection." ], "exact_answer": [ "Vaxchora" ], "type": "factoid", "id": "5e7641a0c6a8763d23000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Vaxchora: The First FDA-Approved Cholera Vaccination in the United States.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29018300", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Vaxchora is the first vaccine approved by the Food and Drug Administration for the prophylaxis of cholera infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29018300", "endSection": "abstract" } ] }, { "body": "List 3 PD-L1 inhibitors on the market as of 2018.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29571563" ], "ideal_answer": [ "Atezolizumab (Tecentriq), Avelumab (Bavencio), and Durvalumab (Imfinzi) are PD-L1 inhibitors" ], "exact_answer": [ [ "Atezolizumab (Tecentriq)" ], [ "Avelumab (Bavencio)" ], [ "Durvalumab (Imfinzi)" ] ], "type": "list", "id": "5e494b0e6d0a277941000007", "snippets": [ { "offsetInBeginSection": 312, "offsetInEndSection": 441, "text": "PD-L1 ICI, such as atezolizumab (TECENTRIQ\u00ae, Genentech), durvalumab (IMFINZI\u00ae, Astra-Zeneca), and avelumab (BAVENCIO\u00ae, EMD Serono", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29571563", "endSection": "abstract" } ] }, { "body": "Are there negative enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1883358", "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "http://www.ncbi.nlm.nih.gov/pubmed/25605944", "http://www.ncbi.nlm.nih.gov/pubmed/8770895", "http://www.ncbi.nlm.nih.gov/pubmed/2481227", "http://www.ncbi.nlm.nih.gov/pubmed/9038208", "http://www.ncbi.nlm.nih.gov/pubmed/2539381", "http://www.ncbi.nlm.nih.gov/pubmed/2968500" ], "ideal_answer": [ "Yes, negative enhancers are also called gene silencers.", "Yes, there are. There is a gene called the CANP mL gene, which is responsible for muscle type regulation. It is a negative enhancer.", "Yes, they are genomic regions that are dense in negative regulatory elements.", "Yes. Negative enhancers are enhancers that negatively regulate gene expression by physically blocking transcription of a subset of genes, often immobilizing transcriptional machinery.", "Yes. Numerous studies suggest that negative enhancers are present in eukaryotic genomes and play key roles in gene expression.", "Yes, there are. There is a gene called the CANP mL gene, which is responsible for muscle type regulation. It has a positive and a negative enhancer. The positive enhancer gene controls muscle type, while the negative one controls muscle growth.", "Yes. There are numerous studies of gene regulation in which enhancers are found to be negative enhancers, either because they negatively regulate transcription, or are absent or have a limited function." ], "exact_answer": "yes", "type": "yesno", "id": "5d35eb01b3a638076300000f", "snippets": [ { "offsetInBeginSection": 103, "offsetInEndSection": 150, "text": "Role of a YY-1 factor-binding negative enhancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9038208", "endSection": "title" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1156, "text": "Mutations targeted to the CArG-like motif abolished the suppressive effect of the negative enhancer and the inducibility of the promoter during myogenic differentiation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9038208", "endSection": "abstract" }, { "offsetInBeginSection": 1158, "offsetInEndSection": 1299, "text": "Our results suggest that the activity of the negative enhancer may determine the level of expression of the COX Vb gene in different tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9038208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Coordinate regulation of Drosophila tropomyosin gene expression is controlled by multiple muscle-type-specific positive and negative enhancer elements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "endSection": "title" }, { "offsetInBeginSection": 375, "offsetInEndSection": 534, "text": "enhancer regions contain multiple muscle-type-specific positive and negative cis-acting elements which together contribute toward full expression of the gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1286, "text": "We also show that this somatic/visceral muscle element(s) can be repressed through an adjacent negative control region, suggesting that the regulation of expression in these muscles is under dual control during both phases of myogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1544, "text": "We propose a model in which transcriptional regulation of the Drosophila TmI gene is controlled by the cooperative interaction of multiple positive and negative cis-acting regulatory elements that control the temporal and muscle-type pattern of expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2539381", "endSection": "title" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1143, "text": "Upstream of the promoter region are tandemly reiterated multiple regulatory regions (-2.5k to -690, -690 to -460, -460 to -260, and -260 to -202), each of which negatively regulates the CANP mL gene promoter as well as heterologous promoters in an orientation-independent manner", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2539381", "endSection": "abstract" }, { "offsetInBeginSection": 1313, "offsetInEndSection": 1494, "text": "he negative regulation of transcription mediated by these reiterated cis-acting elements and trans-acting factor(s) may play an essential role in the expression of the CANP mL gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2539381", "endSection": "abstract" }, { "offsetInBeginSection": 779, "offsetInEndSection": 1208, "text": "Although LDB1-dependent activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of metastasis-associated 1 family, member 2, a component of the nucleosome remodeling deacetylase complex, on these negative enhancers, required for the repressive enhancer function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25605944", "endSection": "abstract" }, { "offsetInBeginSection": 1410, "offsetInEndSection": 1640, "text": "The site was similar to silencers, or negative enhancers, in that it acted to repress transcription from outside the transcribed region, but was distinct in that the function of a canonical silencer was independent of orientation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2481227", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1249, "text": "Clones in which the transgene was down-regulated by dexamethasone survived and were designated AtT-20/NET (for negative enhancer trap).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8770895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "The E1a gene of adenovirus encodes two proteins, 289 and 243 amino acids long, which have positive (transactivator) and negative (enhancer repressor) RNA polymerase II transcriptional regulatory properties and cell transformation activities including cooperation with an activated ras gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2968500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2539381", "endSection": "title" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1144, "text": "Upstream of the promoter region are tandemly reiterated multiple regulatory regions (-2.5k to -690, -690 to -460, -460 to -260, and -260 to -202), each of which negatively regulates the CANP mL gene promoter as well as heterologous promoters in an orientation-independent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2539381", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1311, "text": "The presence of a cellular factor(s) mediating the action of these positive (promoter) and negative regulatory elements was suggested by an in vivo competition assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2539381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "We have previously identified a silencer (negative enhancer) in glutathione transferase P (GST-P) gene which is strongly and specifically induced during hepatocarcinogenesis of the rat. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1883358", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 795, "text": "The possibility that SF-B/LAP/IL6-DBP functions as a dual positive and negative regulator is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1883358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Coordinate regulation of Drosophila tropomyosin gene expression is controlled by multiple muscle-type-specific positive and negative enhancer elements", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "endSection": "title" }, { "offsetInBeginSection": 360, "offsetInEndSection": 533, "text": "Together these enhancer regions contain multiple muscle-type-specific positive and negative cis-acting elements which together contribute toward full expression of the gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1544, "text": "We also show that this somatic/visceral muscle element(s) can be repressed through an adjacent negative control region, suggesting that the regulation of expression in these muscles is under dual control during both phases of myogenesis. We propose a model in which transcriptional regulation of the Drosophila TmI gene is controlled by the cooperative interaction of multiple positive and negative cis-acting regulatory elements that control the temporal and muscle-type pattern of expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8405675", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1297, "text": "Mutations targeted to the CArG-like motif abolished the suppressive effect of the negative enhancer and the inducibility of the promoter during myogenic differentiation. Our results suggest that the activity of the negative enhancer may determine the level of expression of the COX Vb gene in different tissue", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9038208", "endSection": "abstract" } ] }, { "body": "What is the function of WAPL protein on cohesin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24055153", "http://www.ncbi.nlm.nih.gov/pubmed/27797072", "http://www.ncbi.nlm.nih.gov/pubmed/17141150", "http://www.ncbi.nlm.nih.gov/pubmed/29447171", "http://www.ncbi.nlm.nih.gov/pubmed/29217591", "http://www.ncbi.nlm.nih.gov/pubmed/28424523", "http://www.ncbi.nlm.nih.gov/pubmed/17112726", "http://www.ncbi.nlm.nih.gov/pubmed/23034634", "http://www.ncbi.nlm.nih.gov/pubmed/17113138", "http://www.ncbi.nlm.nih.gov/pubmed/28475897" ], "ideal_answer": [ "Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase We show that the human ortholog of Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase.", "Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase.It promotes the release of cohesin from chromosomes during both interphase and mitosis.", "Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. We show that the human ortholog of Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase." ], "exact_answer": [ "Wapl is a cohesin unloading factor" ], "type": "factoid", "id": "5d35be1cb3a6380763000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17112726", "endSection": "title" }, { "offsetInBeginSection": 761, "offsetInEndSection": 909, "text": "We show that the human ortholog of Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17112726", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1419, "text": "Conversely, overexpression of Wapl causes premature separation of sister chromatids. Wapl physically associates with cohesin in HeLa-cell nuclear extracts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17112726", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Wapl controls the dynamic association of cohesin with chromatin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17113138", "endSection": "title" }, { "offsetInBeginSection": 379, "offsetInEndSection": 997, "text": "Here, we show that the interaction between cohesin and chromatin is controlled by Wapl, a protein implicated in heterochromatin formation and tumorigenesis. Wapl is associated with cohesin throughout the cell cycle, and its depletion blocks cohesin dissociation from chromosomes during the early stages of mitosis and prevents the resolution of sister chromatids until anaphase, which occurs after a delay. Wapl depletion also increases the residence time of cohesin on chromatin in interphase. Our data indicate that Wapl is required to unlock cohesin from a particular state in which it is stably bound to chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17113138", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 386, "text": "In recent articles published in Cell and Current Biology, the characterization of Wapl, a newly identified cohesin-interacting protein, suggests that a dynamic interaction between the cohesin complex and chromatin is important for normal regulation of sister chromatid cohesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17141150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Wapl protein regulates binding of the cohesin complex to chromosomes during interphase and helps remove cohesin from chromosomes at mitosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034634", "endSection": "abstract" }, { "offsetInBeginSection": 1088, "offsetInEndSection": 1316, "text": "Wapl-AG was found to increase the stability of cohesin binding to polytene chromosomes. Our data suggest that increasing cohesin stability interferes with PcG silencing at genes that are co-regulated by cohesin and PcG proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23034634", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 236, "text": ". First, during prophase and prometaphase, the bulk of cohesin is driven from chromosome arms by the cohesin antagonist WAPL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055153", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1245, "text": "s a consequence, WAPL-depleted cells undergo anaphase with segregation errors, including both lagging chromosomes and catenanes, resulting in micronuclei and DNA damage. Stable WAPL depletion arrests cells in a p53-dependent manner but causes p53-deficient cells to become highly aneuploid. Our data show that the WAPL-dependent prophase pathway is essential for proper chromosome segregation and is crucial to maintain genomic integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24055153", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 621, "text": "cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217591", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1181, "text": "ohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28475897", "endSection": "title" }, { "offsetInBeginSection": 352, "offsetInEndSection": 481, "text": "Cohesin's DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28475897", "endSection": "abstract" }, { "offsetInBeginSection": 915, "offsetInEndSection": 1027, "text": "We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28475897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424523", "endSection": "title" }, { "offsetInBeginSection": 602, "offsetInEndSection": 737, "text": "the distribution of cohesin in the mouse genome depends on transcription, CTCF and the cohesin release factor Wings apart-like (Wapl). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424523", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1100, "text": "In the absence of both CTCF and Wapl, cohesin accumulates in up to 70 kilobase-long regions at 3'-ends of active genes, in particular if these converge on each other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28424523", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 505, "text": "the cohesin regulator Wapl promotes the release of cohesin from chromosomes during both interphase and mitosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27797072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29447171", "endSection": "title" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1404, "text": "Pds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29447171", "endSection": "abstract" } ] }, { "body": "What is romiplostim targeting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29191945", "http://www.ncbi.nlm.nih.gov/pubmed/28548028" ], "ideal_answer": [ "Romiplostim (ROM) is a thrombopoietin (TPO)-receptor-agonist approved for treatment of adults with chronic immune thrombocytopenia (ITP)." ], "exact_answer": [ "Romiplostim (ROM) is a thrombopoietin (TPO)-receptor-agonist" ], "type": "factoid", "id": "5e5d24811af46fc130000006", "snippets": [ { "offsetInBeginSection": 266, "offsetInEndSection": 403, "text": "Romiplostim (ROM) is a thrombopoietin (TPO)-receptor-agonist approved for treatment of adults with chronic immune thrombocytopenia (ITP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28548028", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 792, "text": " the THPO-mimetic romiplostim", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29191945", "endSection": "abstract" } ] }, { "body": "Please list 3 drugs that have EGFR as their primary target.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28337370", "http://www.ncbi.nlm.nih.gov/pubmed/29725456", "http://www.ncbi.nlm.nih.gov/pubmed/29680500", "http://www.ncbi.nlm.nih.gov/pubmed/27655662", "http://www.ncbi.nlm.nih.gov/pubmed/28416737" ], "ideal_answer": [ "There are a number of drugs that target EGFR. The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib)", "Cetuximab, erlotinib and gefitinib are 3 drugs that have EGFR as their primary target.", "The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib)" ], "exact_answer": [ [ "nimotuzumab" ], [ "Cetuximab" ], [ "zalutumumab" ], [ "Panitumumab" ], [ "Dacomitinib" ], [ "afatinib" ], [ "gefitinb" ], [ "Erlotinib" ], [ "lapatinib" ], [ "osimertinib" ] ], "type": "list", "id": "5e4be9496d0a27794100002a", "snippets": [ { "offsetInBeginSection": 199, "offsetInEndSection": 389, "text": "To that effect, targeted therapies to EGFR such as Cetuximab, Panitumumab-monoclonal antibodies and Gefitinib, Erlotinib-tyrosine kinase inhibitors have had success in therapeutic scenarios.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29680500", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 778, "text": "Two important strategies that have attenuated lung cancers were through treatments with EGFR-tyrosine kinase-inhibitors, erlotinib and gefitinib, or EGFR-neutralizing antibodies, cetuximab and bevacizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28337370", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 728, "text": "The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29725456", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 773, "text": "EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib), of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal antibody cetuximab, and of third-generation EGFR-TKI (osimertinib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28416737", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 359, "text": "Dual targeting of EGFR using one monoclonal antibody (mAb; cetuximab or panitumumab) and one tyrosine kinase inhibitor (EGFR-TKI; gefitinib or erlotinib) is a potential therapeutic approach. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27655662", "endSection": "abstract" } ] }, { "body": "What is the role of STAG1/STAG2 proteins in differentiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18276799", "http://www.ncbi.nlm.nih.gov/pubmed/12034751", "http://www.ncbi.nlm.nih.gov/pubmed/27298259", "http://www.ncbi.nlm.nih.gov/pubmed/26997282", "http://www.ncbi.nlm.nih.gov/pubmed/15361841", "http://www.ncbi.nlm.nih.gov/pubmed/21589869", "http://www.ncbi.nlm.nih.gov/pubmed/28430577", "http://www.ncbi.nlm.nih.gov/pubmed/19822671", "http://www.ncbi.nlm.nih.gov/pubmed/29867216" ], "ideal_answer": [ "STAG1/STAG2 proteins are tumour suppressor proteins that suppress cell proliferation and are essential for differentiation.", "involved in the g2-m transition", "STAG1/STAG2 proteins are tumour suppressor proteins that suppress cell proliferation and differentiation.", "The expression of STAG1 mRNA was induced in response to various genotoxic stresses in a p53-dependent manner; moreover, enforced expression of STAG1 led to apoptosis in several additional cancer cell lines. The simultaneous blocking of STAG1 and STAG2 significantly reduces cell proliferation. STAG1 preferentially contributes to the stabilization of topologically associating domain boundaries together with CTCF, whereas STAG2 promotes cell-type-specific contacts between enhancers and promoters independently of CTCF." ], "exact_answer": [ "meiosis and cell proliferation" ], "type": "factoid", "id": "5d35dfbdb3a638076300000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12034751", "endSection": "title" }, { "offsetInBeginSection": 118, "offsetInEndSection": 414, "text": " Two members of this family, STAG1/SA1 and STAG2/SA2,double dagger are classified as mitotic cohesins, as they are found in human somatic cells and in Xenopus laevis as components of the cohesin(SA1) and cohesin(SA2) complexes, in which the shared subunits are Rad21/SCC1, SMC1 and SMC3 proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12034751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Identification of STAG1 as a key mediator of a p53-dependent apoptotic pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361841", "endSection": "title" }, { "offsetInBeginSection": 509, "offsetInEndSection": 643, "text": "The STAG1 gene was one of the transcripts showing higher expression levels in cells infected with Ad-p53-121F as opposed to Ad-wtp53. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361841", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 979, "text": "the expression of STAG1 mRNA was induced in response to various genotoxic stresses in a p53-dependent manner; moreover, enforced expression of STAG1 led to apoptosis in several additional cancer cell lines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15361841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19822671", "endSection": "title" }, { "offsetInBeginSection": 229, "offsetInEndSection": 357, "text": "Here, we show that cohesin(SA1) and cohesin(SA2) are differentially required for telomere and centromere cohesion, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19822671", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1358, "text": "These results suggest that at telomeres cohesion relies on the molecular interplay between TRF1 and SA1 to promote DNA-DNA pairing, while along chromosomal arms the core cohesin assembly might also depend on SA1 1D diffusion on DNA and sequence-specific DNA binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27298259", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 572, "text": " Here we show that the loss-of-function of STAG2, a core component of cohesin and an emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells on its paralog STAG1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430577", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 950, "text": "In all cases, we observed that the simultaneous blocking of STAG1 and STAG2 significantly reduces cell proliferation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28430577", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 1041, "text": "cohesin-SA1 preferentially contributes to the stabilization of topologically associating domain boundaries together with CTCF, whereas cohesin-SA2 promotes cell-type-specific contacts between enhancers and promoters independently of CTCF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29867216", "endSection": "abstract" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1108, "text": "Expression analyses of Gli1-expressing NSCs identified significant induction of Gadd45a and decreased cyclin A2 and Stag1 mRNA, genes involved in the G2-M transition and apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18276799", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1346, "text": "Finally, we show that Nanog physically interacts with the cohesin or cohesin interacting proteins STAG1 and WAPL further substantiating this association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21589869", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 547, "text": "A striking finding was the identification of members of the cohesin complex (STAG2, RAD21, STAG1, and SMC3) among the top 20 genes from the screen. Upon individual validation of these cohesin genes, we found that their knockdown led to an immediate expansion of cells with an HSC phenotype in\u00a0vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26997282", "endSection": "abstract" } ] }, { "body": "What can we measure with the TSA-Seq method?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30154186" ], "ideal_answer": [ "Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler. TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling.", "TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler. ", "TSA-Seq is a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling.", "mean chromosomal distances" ], "type": "summary", "id": "5d35ca5eb3a6380763000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "title" }, { "offsetInBeginSection": 219, "offsetInEndSection": 498, "text": "TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "abstract" } ] }, { "body": "Which method is behind HipMCL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29315405" ], "ideal_answer": [ "HipMCL is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks. Despite its popularity, MCL's scalability to cluster large datasets still remains a bottleneck due to high running times and memory demands.", "While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks. HipMCL is based on MPI and OpenMP and is freely available under a modified BSD license.", "While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks. Despite its popularity, MCL's scalability to cluster large datasets still remains a bottleneck due to high running times and memory demands. High-performance MCL (HipMCL) offers a parallel implementation of the original MCL algorithm that can run on distributed-memory computers. By exploiting distributed-memory environments, HipMCL clusters large-scale networks several orders of magnitude faster than MCL and enables clustering of even bigger networks. HipMCL is based on MPI and OpenMP and is freely available under a modified BSD license.", "While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks. Despite its popularity, MCL's scalability to cluster large datasets still remains a bottleneck due to high running times and memory demands. HipMCL is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks.", "HipMCL (HipClustering) is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks.", "HipMCL is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks." ], "exact_answer": [ "Markov Clustering", "MCL" ], "type": "factoid", "id": "5e4ada686d0a277941000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "HipMCL: a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29315405", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1305, "text": "Biological networks capture structural or functional properties of relevant entities such as molecules, proteins or genes. Characteristic examples are gene expression networks or protein-protein interaction networks, which hold information about functional affinities or structural similarities. Such networks have been expanding in size due to increasing scale and abundance of biological data. While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks. Despite its popularity, MCL's scalability to cluster large datasets still remains a bottleneck due to high running times and memory demands. Here, we present High-performance MCL (HipMCL), a parallel implementation of the original MCL algorithm that can run on distributed-memory computers. We show that HipMCL can efficiently utilize 2000 compute nodes and cluster a network of \u223c70 million nodes with \u223c68 billion edges in \u223c2.4 h. By exploiting distributed-memory environments, HipMCL clusters large-scale networks several orders of magnitude faster than MCL and enables clustering of even bigger networks. HipMCL is based on MPI and OpenMP and is freely available under a modified BSD license.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29315405", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 610, "text": "While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29315405", "endSection": "abstract" } ] }, { "body": "What is the function of CR elements in B-cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23030360", "http://www.ncbi.nlm.nih.gov/pubmed/305444", "http://www.ncbi.nlm.nih.gov/pubmed/23555858", "http://www.ncbi.nlm.nih.gov/pubmed/1083874" ], "ideal_answer": [ " After addition of culture supernatant from BCG-activated macrophages CR- B cells cooperate with both unprimed and primed T helper cells.", "The SR/CR mouse phenotype, first described in 1999 in BALB/c and later bred into C57BL/6 mice, is resistant to cancer formation following high doses of cancer cells administered intraperitoneally.", "CR elements are subtelomeric protein complexes that repress translation of a subset of RNAs in response to abiotic stress and can mediate diverse physiological and developmental processes in B- cells." ], "type": "summary", "id": "5d35d03ab3a6380763000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "B cells that carry the complement receptor (CR+) were separated from B cells that lack the complement receptor (CR-) by velocity sedimentation or by passage through C-coated Sephadex columns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/305444", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 814, "text": " CR- B cells responded with a delay of approximately 24 hr as compared with the response of CR+ B cells. The implications to the ontogenetic status of CR+ and CR- B subpopulations are discussed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/305444", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 961, "text": " After addition of culture supernatant from BCG-activated macrophages CR- B cells cooperate with both unprimed and primed T helper cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1083874", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 823, "text": "CR- B cells cooperate with primed but not with unprimed T cells provided macrophages are added to cultures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1083874", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 292, "text": "SR/CR (spontaneous regression/complete resistance) mouse model in which natural resistance to a variety of cancer types appeared to be inherited in SR/CR strains of BALB/c and C57BL/6 mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555858", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 896, "text": "The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+ leukocytes and B-cells from SR/CR mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23555858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "The SR/CR mouse phenotype, first described in 1999 in BALB/c and later bred into C57BL/6 mice, is resistant to cancer formation following high doses of cancer cells administered intraperitoneally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23030360", "endSection": "abstract" } ] }, { "body": "What is drug target for olaparib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29129088", "http://www.ncbi.nlm.nih.gov/pubmed/30660828", "http://www.ncbi.nlm.nih.gov/pubmed/30486888" ], "ideal_answer": [ "Olaparib(Lynparza) is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair.", "Olaparib is a Poly(ADP-ribose) Polymerase (PARP) Inhibitor" ], "exact_answer": [ "poly ADP ribose polymerase (PARP)" ], "type": "factoid", "id": "5e42d1a748dab47f26000010", "snippets": [ { "offsetInBeginSection": 1409, "offsetInEndSection": 1471, "text": "PARP inhibition with olaparib, warrants further investigation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29129088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 37, "text": "Olaparib is a PARP inhibitor (PARPi).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30660828", "endSection": "abstract" } ] }, { "body": "What virus is the Gardisil vaccine used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22777095" ], "ideal_answer": [ "Gardisil is a quadrivalent HPV vaccine would have been useful in the prevention of infections with human papillomavirus.", "Gardisil is a 4-component vaccine against capsular HPV 16 (4C HPV16), which has recently been licensed in Europe, Canada and Australia.", "Gordisil is a 4-component vaccine against capsular Meningococcus serogroup B (4CMenB), which has recently been licensed in Europe, Canada and Australia.", "Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections ", "Gardisil is a 16-component vaccine against human papillomavirus (HPV), which has recently been licensed in Europe, Canada and Australia.", "Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections" ], "type": "summary", "id": "5e3df59348dab47f26000006", "snippets": [ { "offsetInBeginSection": 1177, "offsetInEndSection": 1291, "text": "Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777095", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1296, "text": "Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777095", "endSection": "abstract" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1292, "text": "Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777095", "endSection": "abstract" } ] }, { "body": "Which cells mature in the human thymus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12218105", "http://www.ncbi.nlm.nih.gov/pubmed/11994452", "http://www.ncbi.nlm.nih.gov/pubmed/26635029", "http://www.ncbi.nlm.nih.gov/pubmed/14768939", "http://www.ncbi.nlm.nih.gov/pubmed/27817026", "http://www.ncbi.nlm.nih.gov/pubmed/18955544", "http://www.ncbi.nlm.nih.gov/pubmed/16579866", "http://www.ncbi.nlm.nih.gov/pubmed/27043411", "http://www.ncbi.nlm.nih.gov/pubmed/6605224" ], "ideal_answer": [ "Thymus progenitor cells mature in the human thymus through differentiation into cardiomyocytes and fibroblasts.", "Late stages of T cell maturation in the thymus involve NF-kB and tonic type I interferon signaling. NF-kB and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells.", "late stages of t cell maturation in the thymus involve nf-kb and tonic type i interferon signals", "NF-kB and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells.", "The mammalian thymus is an important post-translational organ that plays a pivotal role in the development of the human immune system. Thymocytes, which represent 50% of the cells in the human body, mature into cardiomyocytes and T cells.", "T cells mature in the human thymus; in particular, type T cells." ], "exact_answer": [ "T-cells", "T-lymphocytes" ], "type": "factoid", "id": "5d36a9507bc3fee31f000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Late stages of T cell maturation in the thymus involve NF-\u03baB and tonic type I interferon signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043411", "endSection": "title" }, { "offsetInBeginSection": 868, "offsetInEndSection": 973, "text": "NF-\u03baB and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The inhibition of dopamine synthesis in fetuses changes the pattern of T-lymphocyte maturation in the thymus of adult rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27817026", "endSection": "title" }, { "offsetInBeginSection": 368, "offsetInEndSection": 583, "text": " Pharmacological inhibition of catecholamine synthesis in the crucial period of thymus development leads to long-term changes in the T-system immunity due to increased production of natural regulatory T-lymphocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27817026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26635029", "endSection": "title" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1298, "text": "This first ex vivo analysis of human antigen-specific thymocytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26635029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "CD44 promotes progenitor homing into the thymus and T cell maturation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18955544", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Delayed functional maturation of natural regulatory T cells in the medulla of postnatal thymus: role of TSLP.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16579866", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Effects of nicotine exposure on T cell development in fetal thymus organ culture: arrest of T cell maturation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218105", "endSection": "title" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1476, "text": "Furthermore, d-tubocurarine alone blocked the development of both immature and mature murine thymocytes, suggesting the presence of an endogenous ligand that may engage nicotinic acetylcholine receptors on developing thymocytes and influence the course of normal thymic ontogeny.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218105", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 877, "text": "However, both DP T cell subsets have an intrathymic origin since they appear in the recent thymic emigrant population after injection of FITC intrathymically.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11994452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "T-cell maturation in the human thymus and tonsil", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6605224", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Expression of the HPV16E7 oncoprotein by thymic epithelium is accompanied by disrupted T cell maturation and a failure of the thymus to involute with age.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14768939", "endSection": "title" }, { "offsetInBeginSection": 587, "offsetInEndSection": 735, "text": "Thymocytes with reduced levels of expression of CD4 and/or CD8 were more abundant in transgenic (tg) mice and became increasingly more so with age. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14768939", "endSection": "abstract" } ] }, { "body": "What are the eRNA-producing centers (EPCs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30447999" ], "ideal_answer": [ "Active enhancers in mammals produce enhancer RNAs (eRNAs) that are bidirectionally transcribed, unspliced, and unstable. Enhancer regions are also enriched with long noncoding RNA (lncRNA) transcripts, which are typically spliced and substantially more stable. DNase hypersensitive sites with evidence of bidirectional transcription are called eRNA-producing centers (EPCs). EPCs found very close to transcription start sites of lncRNAs exhibit attributes of both enhancers and promoters, including distinctive DNA motifs and a characteristic chromatin landscape. These EPCs are associated with higher enhancer activity, driven at least in part by the presence of conserved, directional splicing signals that promote lncRNA production, pointing at a causal role of lncRNA processing in enhancer activity." ], "type": "summary", "id": "5e46fef23f54159529000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1067, "text": "Active enhancers in mammals produce enhancer RNAs (eRNAs) that are bidirectionally transcribed, unspliced, and unstable. Enhancer regions are also enriched with long noncoding RNA (lncRNA) transcripts, which are typically spliced and substantially more stable. In order to explore the relationship between these two classes of RNAs, we analyzed DNase hypersensitive sites with evidence of bidirectional transcription, which we termed eRNA-producing centers (EPCs). EPCs found very close to transcription start sites of lncRNAs exhibit attributes of both enhancers and promoters, including distinctive DNA motifs and a characteristic chromatin landscape. These EPCs are associated with higher enhancer activity, driven at least in part by the presence of conserved, directional splicing signals that promote lncRNA production, pointing at a causal role of lncRNA processing in enhancer activity. Together, our results suggest that the conserved ability of some enhancers to produce lncRNAs augments their activity in a manner likely mediated through lncRNA maturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30447999", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 464, "text": "In order to explore the relationship between these two classes of RNAs, we analyzed DNase hypersensitive sites with evidence of bidirectional transcription, which we termed eRNA-producing centers (EPCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30447999", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 472, "text": "In order to explore the relationship between these two classes of RNAs , we analyzed DNase hypersensitive sites with evidence of bidirectional transcription , which we termed eRNA-producing centers ( EPCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30447999", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 465, "text": "In order to explore the relationship between these two classes of RNAs, we analyzed DNase hypersensitive sites with evidence of bidirectional transcription, which we termed eRNA-producing centers (EPCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30447999", "endSection": "abstract" } ] }, { "body": "Describe Brain Radiation Information Data Exchange (BRIDE) approach", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27170263" ], "ideal_answer": [ "BRIDE (Brain Radiation Information Data Exchange) is a data integration platform that acts as a knowledge broker for LDIR researchers to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics." ], "type": "summary", "id": "5e4adc296d0a277941000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Brain Radiation Information Data Exchange (BRIDE): integration of experimental data from low-dose ionising radiation research for pathway discovery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27170263", "endSection": "title" }, { "offsetInBeginSection": 329, "offsetInEndSection": 980, "text": "We describe a light-weight approach for the storage, analysis and distribution of relevant LDIR omics datasets. The data integration platform, called BRIDE, contains information from the literature as well as experimental information from transcriptomics and proteomics studies. It deploys a hybrid, distributed solution using both local storage and cloud technology.CONCLUSIONS: BRIDE can act as a knowledge broker for LDIR researchers, to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27170263", "endSection": "abstract" } ] }, { "body": "When was vivotif first licenced in Europe?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28515625" ], "ideal_answer": [ "The vaccine vivotif was first licensed in Europe in 1983." ], "exact_answer": [ "1983" ], "type": "factoid", "id": "5e763bd4c6a8763d2300000f", "snippets": [ { "offsetInBeginSection": 798, "offsetInEndSection": 1060, "text": "Vivotif\u00ae is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28515625", "endSection": "abstract" } ] }, { "body": "What is herceptin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15695389", "http://www.ncbi.nlm.nih.gov/pubmed/23830593", "http://www.ncbi.nlm.nih.gov/pubmed/29305325", "http://www.ncbi.nlm.nih.gov/pubmed/29434878", "http://www.ncbi.nlm.nih.gov/pubmed/14666732", "http://www.ncbi.nlm.nih.gov/pubmed/19398090", "http://www.ncbi.nlm.nih.gov/pubmed/15868447", "http://www.ncbi.nlm.nih.gov/pubmed/29544445", "http://www.ncbi.nlm.nih.gov/pubmed/31822364", "http://www.ncbi.nlm.nih.gov/pubmed/29405790", "http://www.ncbi.nlm.nih.gov/pubmed/29163501", "http://www.ncbi.nlm.nih.gov/pubmed/12422054", "http://www.ncbi.nlm.nih.gov/pubmed/29671404", "http://www.ncbi.nlm.nih.gov/pubmed/19593441", "http://www.ncbi.nlm.nih.gov/pubmed/11768602", "http://www.ncbi.nlm.nih.gov/pubmed/25377592", "http://www.ncbi.nlm.nih.gov/pubmed/15087020", "http://www.ncbi.nlm.nih.gov/pubmed/21992561", "http://www.ncbi.nlm.nih.gov/pubmed/22934911", "http://www.ncbi.nlm.nih.gov/pubmed/19497323" ], "ideal_answer": [ "Herceptin is a second generation tyrosine kinase inhibitor, that serves as an effective and approved oral therapy for patients with HER2-positive breast cancer.", "Herceptin is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that binds to HER2 and inhibits HER2 activation. It is approved for the treatment of breast cancer.", "Trastuzumab (Herceptin(r) [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer.", "trastuzumab is the standard of care for her2-positive breast cancer", "Trastuzumab (Herceptin(r) [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. ", "Herceptin is a tyrosine-kinase inhibitor that targets the HER2 receptor oncogene with high affinity and activity. It is approved for treatment of breast cancer." ], "type": "summary", "id": "5e46c7e73f54159529000009", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 177, "text": "Trastuzumab (Herceptin\u00ae [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29544445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "Breast cancer (BCa) is the most common cancer affecting women worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in ~20-25% of invasive ductal breast carcinomas and is associated with the more aggressive phenotype. Herceptin, a humanized antibody against HER2, is a standard therapy in HER2-overexpressing cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29434878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Trastuzumab (Herceptin\u00ae), a monoclonal antibody against the ErbB2 (HER2) receptor, has significantly improved clinical outcomes for HER2+ breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29305325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29405790", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 328, "text": "Trastuzumab (Herceptin), a monoclonal antibody against a membrane-proximal epitope in the extracellular region of erbB2, shows a therapeutic effect against a fraction of erbB2-amplified breast tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15695389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "BACKGROUND & OBJECTIVE\n\nHerceptin is a humanized monoclonal antibody for treating the patients with metastatic breast cancers overexpressing human epidermal growth factor receptor (HER-2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15087020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody against HER2, started for patients with HER2-overexpressing breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14666732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Herceptin (trastuzumab), an anti-HER2 monoclonal antibody, is the first oncogene-targeted therapy to be developed for the treatment of metastatic breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12422054", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 391, "text": "Herceptin, an antihuman epidermal growth factor receptor-2 (anti-HER2) monoclonal antibody, is used to treat HER2 __sup__ + __end_sup__ breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29163501", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 361, "text": "Herceptin is a humanised mouse antibody that targets and inactivates HER-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21992561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "BACKGROUND\n\nHerceptin (trastuzumab) is a humanized monoclonal antibody that is approved for the treatment of metastatic breast cancer patients whose tumors overexpress Her2 (erbB2/neu).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19593441", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 163, "text": "Herceptin is a well-received antibody drug for HER2 positive gastric cancer . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31822364", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 188, "text": "Herceptin is a recombinant humanized Her2 antibody used to treat breast cancer patients with Her2 overexpression . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15868447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Herceptin is a monoclonal antibody against HER2 , which is a member of the epidermal growth factor receptor ( ErbB ) family and is overexpressed in many cancers . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Herceptin is a humanized monoclonal antibody for treating the patients with metastatic breast cancers overexpressing human epidermal growth factor receptor ( HER-2) . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15087020", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 254, "text": "Herceptin is a major drug used to treat HER2 positive breast cancer . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29671404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Herceptin is a humanized antibody that binds to the product of the HER-2 oncogene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11768602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "BACKGROUND\nTrastuzumab (Herceptin(\u00ae)) is a humanized monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2) and is used in the treatment of HER2-overexpressing breast and gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25377592", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 505, "text": "Herceptin is a HER-2 targeted antibody that being widely used for the management of HER-2 positive breast cancer, which demonstrate significant benefits in both the metastatic and adjuvant settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23830593", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 353, "text": "Herceptin is a humanised mouse antibody that targets and inactivates HER-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21992561", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 182, "text": "Herceptin is a recombinant humanized Her2 antibody used to treat breast cancer patients with Her2 overexpression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15868447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Herceptin is a monoclonal antibody against HER2, which is a member of the epidermal growth factor receptor (ErbB) family and is overexpressed in many cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19497323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Herceptin is a humanized monoclonal antibody for treating the patients with metastatic breast cancers overexpressing human epidermal growth factor receptor (HER-2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15087020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Herceptin/Trastuzumab is a humanized IgG1\u03ba light chain antibody used to treat some forms of breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22934911", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 369, "text": "Herceptin, an antihuman epidermal growth factor receptor-2 (anti-HER2) monoclonal antibody, is used to treat HER2+ breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29163501", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Herceptin (trastuzumab) is an adjuvant chemotherapy agent used in treatment of certain breast cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Herceptin (trastuzumab) is a humanized monoclonal antibody that is approved for the treatment of metastatic breast cancer patients whose tumors overexpress Her2 (erbB2/neu).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19593441", "endSection": "abstract" } ] }, { "body": "Has saracatinib been tested in clinical trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "http://www.ncbi.nlm.nih.gov/pubmed/26493492", "http://www.ncbi.nlm.nih.gov/pubmed/26062928", "http://www.ncbi.nlm.nih.gov/pubmed/26009269" ], "ideal_answer": [ "Yes, saracatinib has been tested in multiple clinical trials." ], "exact_answer": "yes", "type": "yesno", "id": "5e540db06d0a277941000053", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Saracatinib as a metastasis inhibitor in metastatic castration-resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD/PCF Prostate Cancer Clinical Trials Consortium Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26493492", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26009269", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26062928", "endSection": "title" }, { "offsetInBeginSection": 322, "offsetInEndSection": 460, "text": "Metastatic colorectal cancer patients who had received one prior treatment and had measurable disease were enrolled in this phase 2 study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26062928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "endSection": "title" }, { "offsetInBeginSection": 599, "offsetInEndSection": 801, "text": "Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1015, "text": "The study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25874001", "endSection": "abstract" } ] }, { "body": "What animal is thought to be the host for the Coronavirus causing MERS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29239118", "http://www.ncbi.nlm.nih.gov/pubmed/30146782", "http://www.ncbi.nlm.nih.gov/pubmed/25791336", "http://www.ncbi.nlm.nih.gov/pubmed/29336306" ], "ideal_answer": [ "The animal thought to be the host for the Coronavirus causing MERS is camels.", "The Virus causing MERS is though to have originated in dromedary camels" ], "exact_answer": [ "camel" ], "type": "factoid", "id": "5e2f4a8bfbd6abf43b00002a", "snippets": [ { "offsetInBeginSection": 1260, "offsetInEndSection": 1437, "text": "hese data demonstrate a genetic link for each of these clusters to a camel and support the hypothesis that human MERS-CoV diversity results from multiple zoonotic introductions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29239118", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 821, "text": "The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30146782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29336306", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 528, "text": " Here, we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29336306", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 704, "text": "ong-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29336306", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 926, "text": " human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29336306", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 291, "text": "While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25791336", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 835, "text": "The exact origin of MERS-CoV remains unknown , but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host , from which human infections may sporadically occur through the zoonotic transmission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30146782", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 292, "text": "While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25791336", "endSection": "abstract" } ] }, { "body": "Which molecules are inhibited by Gilteritinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "http://www.ncbi.nlm.nih.gov/pubmed/31665578", "http://www.ncbi.nlm.nih.gov/pubmed/30053332", "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "http://www.ncbi.nlm.nih.gov/pubmed/31528345", "http://www.ncbi.nlm.nih.gov/pubmed/29669779", "http://www.ncbi.nlm.nih.gov/pubmed/29507660", "http://www.ncbi.nlm.nih.gov/pubmed/30514344", "http://www.ncbi.nlm.nih.gov/pubmed/31069015", "http://www.ncbi.nlm.nih.gov/pubmed/30721452", "http://www.ncbi.nlm.nih.gov/pubmed/31088841", "http://www.ncbi.nlm.nih.gov/pubmed/31454267", "http://www.ncbi.nlm.nih.gov/pubmed/29643105", "http://www.ncbi.nlm.nih.gov/pubmed/30039554", "http://www.ncbi.nlm.nih.gov/pubmed/29498296", "http://www.ncbi.nlm.nih.gov/pubmed/30344940", "http://www.ncbi.nlm.nih.gov/pubmed/28645776" ], "ideal_answer": [ "Gilteritinib is a novel, dual FLT3/AXL inhibitor with promising early phase trial data for acute myeloid leukemia." ], "exact_answer": [ [ "FLT3" ], [ "AXL" ] ], "type": "list", "id": "5e30f8abfbd6abf43b000047", "snippets": [ { "offsetInBeginSection": 437, "offsetInEndSection": 549, "text": "ASP2215 (gilteritinib) is a novel, dual FLT3/AXL inhibitor with promising early phase trial data (NCT02014558). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29498296", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1281, "text": "Ex vivo exposure (n = 30) to FLT3 inhibitors, in particular to the FLT3-specific inhibitor gilteritinib, showed that colony-forming capacity was significantly more reduced in FLT3-ITD-AR \u2265 0.5 compared with ITD-AR-low and ITD- patient samples (P < .001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29669779", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1422, "text": "Furthermore, overexpression of Pim-1 in 32D/TKD enhanced the mTORC1/Mcl-1 pathway and partially protected it from the PI3K/Akt inhibitors or the FLT3 inhibitor gilteritinib to confer the resistance to PI3K/Akt inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29507660", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1127, "text": "Finally, we analyzed bone marrow samples from 80 patients with FLT3-ITD relapsed/refractory AML participating in a trial of a novel FLT3 inhibitor, gilteritinib, and demonstrated a relationship between the mutation burden, as detected by the assay, and overall survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29643105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Gilteritinib, a novel, highly specific, potent fms-like tyrosine kinase 3/AXL inhibitor, demonstrated antileukemic activity in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30039554", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1287, "text": "Combinations of an AXL inhibitor, cabozantinib or gilteritinib, and an EGFR-TKI were more effective against HCC78R cells than monotherapy with an EGFR-TKI or AXL inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Internal tandem duplication (ITD) in Fms-like tyrosine kinase 3 (FLT3) is frequently observed in acute myeloid leukemia (AML). Quizartinib, gilteritinib, and midostaurin are inhibitors against FLT3-ITD that have good efficacy for FLT3-ITD-positive AML patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30344940", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 525, "text": "In this review, we summarized the preclinical and clinical studies on new FLT3 inhibitors, including sorafenib, lestaurtinib, sunitinib, tandutinib, quizartinib, midostaurin, gilteritinib, crenolanib, cabozantinib, Sel24-B489, G-749, AMG 925, TTT-3002, and FF-10101. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30514344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28645776", "endSection": "title" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1458, "text": "In the FLT3 signaling analyses, gilteritinib inhibited FLT3 __sup__ wt __end_sup__ and FLT3-ITD to a similar degree in HEK293 and Ba/F3 cells, and similarly suppressed FLT3 downstream signaling molecules (including ERK1/2 and STAT5) in both the presence and absence of FL in MOLM-13 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Effect of Fms-like tyrosine kinase 3 (FLT3) ligand (FL) on antitumor activity of gilteritinib, a FLT3 inhibitor, in mice xenografted with FL-overexpressing cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 479, "text": "We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28645776", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 409, "text": "Gilteritinib inhibits FLT3 (STK1 or FLK2), AXL (UFO or JTK11) and anaplastic lymphoma kinase (ALK or CD246).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30721452", "endSection": "abstract" }, { "offsetInBeginSection": 4562, "offsetInEndSection": 4768, "text": "These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28645776", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1025, "text": "In contrast to other FLT3 inhibitors, FL stimulation had little effect on growth inhibition or apoptosis induction by gilteritinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 893, "text": "Here, we investigated the effect of FL on the efficacy of gilteritinib, a FLT3 inhibitor, in AML-derived cells __i_tag__ in vitro __end_i_tag__ and in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 660, "text": "Gilteritinib (ASP2215, Xospata) is a small molecule dual inhibitor of FLT3/AXL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31528345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31528345", "endSection": "title" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1038, "text": "Gilteritinib also inhibited FLT3-F691 mutations, although to a lesser degree, in these assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3 -Mutated AML.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31665578", "endSection": "title" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1338, "text": "Co-crystal structure analysis showed that gilteritinib bound to the ATP-binding pocket of FLT3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Effect of Fms-like tyrosine kinase 3 ( FLT3 ) ligand ( FL ) on antitumor activity of gilteritinib , a FLT3 inhibitor , in mice xenografted with FL-overexpressing cells .", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "title" }, { "offsetInBeginSection": 946, "offsetInEndSection": 1217, "text": "In the FLT3 signaling analyses , gilteritinib inhibited FLT3and FLT3-ITD to a similar degree in HEK293 and Ba/F3 cells , and similarly suppressed FLT3 downstream signaling molecules ( including ERK1/2 and STAT5 ) in both the presence and absence of FL in MOLM-13 cells . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 669, "text": "Here , we investigated the effect of FL on the efficacy of gilteritinib , a FLT3 inhibitor , in AML-derived cellsand in mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 803, "text": "In contrast to other FLT3 inhibitors , FL stimulation had little effect on growth inhibition or apoptosis induction by gilteritinib . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 826, "text": "In contrast to other FLT3 inhibitors, FL stimulation had little effect on growth inhibition or apoptosis induction by gilteritinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 694, "text": "Here, we investigated the effect of FL on the efficacy of gilteritinib, a FLT3 inhibitor, in AML-derived cells in vitro and in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "title" }, { "offsetInBeginSection": 541, "offsetInEndSection": 711, "text": "Initial kinase studies showed that gilteritinib, a type I tyrosine kinase inhibitor, was highly selective for both FLT3 and AXL while having weak activity against c-KIT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 541, "text": "The studies reported here evaluated the ability of a novel FLT3/AXL inhibitor, gilteritinib, to block mutated FLT3 in cellular and animal models of AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 540, "text": "The studies reported here evaluated the ability of a novel FLT3/AXL inhibitor, gilteritinib, to block mutated FLT3 in cellular and animal models of AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 710, "text": "Initial kinase studies showed that gilteritinib, a type I tyrosine kinase inhibitor, was highly selective for both FLT3 and AXL while having weak activity against c-KIT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "abstract" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1482, "text": "The decreased FLT3 activity and high intratumor distribution of gilteritinib translated to tumor regression and improved survival in xenograft and intra-bone marrow transplantation models of FLT3-driven AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "abstract" }, { "offsetInBeginSection": 1553, "offsetInEndSection": 1700, "text": "These results indicate that gilteritinib may be an important next-generation FLT3 inhibitor for use in the treatment of FLT3 mutation-positive AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Gilteritinib (Xospata\u00ae) is an orally available small molecule receptor tyrosine kinase inhibitor developed by Astellas Pharma in collaboration with Kotobuki Pharmaceutical for the treatment of acute myeloid leukaemia (AML) harbouring FMS-like tyrosine kinase 3 (FLT3) mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30721452", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 387, "text": "Gilteritinib inhibits FLT3 (STK1 or FLK2), AXL (UFO or JTK11) and anaplastic lymphoma kinase (ALK or CD246).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30721452", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 875, "text": "Gilteritinib is approved in Japan for the treatment of relapsed or refractory AML with FLT3 mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30721452", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 309, "text": "Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31665578", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 474, "text": "The highly potent and selective FLT3 kinase inhibitor gilteritinib is the first tyrosine kinase inhibitor approved as monotherapy for the treatment of relapsed and/or refractory FLT3-mutated AML.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31454267", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 444, "text": "Gilteritinib is a highly-specific, potent FLT3/AXL inhibitor with demonstrated activity against FLT3-ITD and FLT3-TKD mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31069015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Gilteritinib is a potent and selective FLT3 kinase inhibitor with single-agent clinical efficacy in relapsed/refractory FLT3-mutated acute myeloid leukemia (AML).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31088841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Gilteritinib, a novel, highly specific, potent fms-like tyrosine kinase 3/AXL inhibitor, demonstrated antileukemic activity in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30039554", "endSection": "abstract" } ] }, { "body": "Is \u03b1CGRP a member of the CGRP family?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29501724" ], "ideal_answer": [ "Yes, aCGRP, a 37-residue-long peptide hormone, is a novel amyloidogenic member of the CGRP family.", "Yes. aCGRP is a member of the CGRP family.", "Yes, aCGRP is a member of the CGRP family." ], "exact_answer": "yes", "type": "yesno", "id": "5e500d8c6d0a277941000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "\u03b1CGRP, another amyloidogenic member of the CGRP family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501724", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 873, "text": "Therefore, in this work, we investigated the amyloidogenic profile of \u03b1CGRP, a 37-residue-long peptide hormone, utilizing both biophysical experimental techniques and Molecular Dynamics simulations. These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the \u03b1CGRP polymerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501724", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 873, "text": "These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the \u03b1CGRP polymerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501724", "endSection": "abstract" }, { "offsetInBeginSection": 727, "offsetInEndSection": 874, "text": "These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the \u03b1CGRP polymerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501724", "endSection": "abstract" } ] }, { "body": "Which is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "http://www.ncbi.nlm.nih.gov/pubmed/30063981" ], "ideal_answer": [ "Loss-of-function nuclear factor kB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.", "Heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of common variable immunodeficiency (CVID), which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells", "Loss-of-function nuclear factor kB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans.", "Heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of common variable immunodeficiency (CVID), which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.", "Heterozygous loss-of-function nuclear factor kB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells." ], "exact_answer": [ "Heterozygous loss-of-function nuclear factor \u03baB subunit 1 (NFKB1) variants" ], "type": "factoid", "id": "5e51dc516d0a27794100003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Loss-of-function nuclear factor \u03baB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1020, "text": "The genetic cause of primary immunodeficiency disease (PID) carries prognostic information.OBJECTIVE: We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource-Rare Diseases cohort.METHODS: In the predominantly European study population of principally sporadic unrelated PID cases (n\u00a0=\u00a0846), a novel Bayesian method identified nuclear factor \u03baB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n\u00a0=\u00a0390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex\u00a0vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "abstract" }, { "offsetInBeginSection": 1747, "offsetInEndSection": 1961, "text": "We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Monoallelic loss-of-function mutations in NFKB1 were recently recognized as the most common monogenic cause of common variable immunodeficiency (CVID).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30063981", "endSection": "abstract" } ] }, { "body": "List 3 human diseases caused by viruses in the family Paramyxoviridae.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29110978", "http://www.ncbi.nlm.nih.gov/pubmed/10717292", "http://www.ncbi.nlm.nih.gov/pubmed/22065774", "http://www.ncbi.nlm.nih.gov/pubmed/27110811", "http://www.ncbi.nlm.nih.gov/pubmed/17230540", "http://www.ncbi.nlm.nih.gov/pubmed/15318694", "http://www.ncbi.nlm.nih.gov/pubmed/21915289", "http://www.ncbi.nlm.nih.gov/pubmed/18453612", "http://www.ncbi.nlm.nih.gov/pubmed/22531181", "http://www.ncbi.nlm.nih.gov/pubmed/25595799", "http://www.ncbi.nlm.nih.gov/pubmed/25965801", "http://www.ncbi.nlm.nih.gov/pubmed/17410634", "http://www.ncbi.nlm.nih.gov/pubmed/3496981", "http://www.ncbi.nlm.nih.gov/pubmed/15699418", "http://www.ncbi.nlm.nih.gov/pubmed/28361207", "http://www.ncbi.nlm.nih.gov/pubmed/30866768", "http://www.ncbi.nlm.nih.gov/pubmed/20552729", "http://www.ncbi.nlm.nih.gov/pubmed/19445268", "http://www.ncbi.nlm.nih.gov/pubmed/15330446", "http://www.ncbi.nlm.nih.gov/pubmed/24488776" ], "ideal_answer": [ "Measles, mumps and encephalitis are diseases caused by viruses in the family Paramyxoviridae.", "Viruses in the family Paramyxoviridae can cuase , measles, mumps and encephalitis as well as respiratory illness in humans." ], "exact_answer": [ [ "measles" ], [ "mumps" ], [ "encephalitis" ], [ "respiratory disease" ], [ "newcastle disease" ] ], "type": "list", "id": "5e4163b848dab47f2600000f", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 103, "text": ": Previous controversy was generated over the hypothesis that a paramyxovirus such as measles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17230540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Measles are a systemic infectious disease caused by a single stranded ribonucleic acid virus (measles virus) from the paramyxovirus family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19445268", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 46, "text": "Mumps is a Paramyxoviridae virus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29110978", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 545, "text": "Since chronic paramyxovirus infection with measles is known to be accompanied by increased production of antiviral antibodies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Nipah virus (NiV) is a highly pathogenic paramyxovirus which causes fatal encephalitis in up to 75% of infected humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20552729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Measles is caused by the paramyxovirus which spreads through airborne droplets", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15318694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Newcastle disease virus (NDV) is classified as a member of the superfamily Mononegavirales in the family Paramyxoviridae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10717292", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 638, "text": "Many of these identified genes were also required for infection by two other NS RNA viruses, the lymphocytic choriomeningitis virus of the Arenaviridae family and human parainfluenza virus type 3 of the Paramyxoviridae family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22065774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Measles virus ( MeV) , a highly contagious member of the Paramyxoviridae family , causes measles in humans . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27110811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The human metapneumovirus ( hMPV ) is a newly reported respiratory virus belonging to the Paramyxoviridae family that has been associated with bronchiolitis and pneumonia in young children . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15699418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Two members of the morbillivirus genus of the family Paramyxoviridae , canine distemper virus ( CDV ) and measles virus ( MV) , are well-known for their ability to cause a chronic demyelinating disease of the CNS in their natural hosts , dogs and humans , respectively . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17410634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Respiratory syncytial virus ( RSV ) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children , yet no highly effective treatment or vaccine is available. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25965801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Human respiratory syncytial virus ( RSV) , a member of the Paramyxoviridae family , is the most important viral agent of pediatric respiratory tract disease worldwide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18453612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Respiratory syncytial virus ( RSV) , an RNA virus in the family Paramyxoviridae , causes respiratory disease in humans . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15330446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Measles virus ( MV ) is a member of the Paramyxoviridae family and an important human pathogen causing strong immunosuppression in affected individuals and a considerable number of deaths worldwide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21915289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Hendra ( HeV ) and Nipah ( NiV ) viruses ( genus Henipavirus ( HNV; family Paramyxoviridae ) are emerging zoonotic agents that can cause severe respiratory distress and acute encephalitis in humans . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24488776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Many of the common respiratory illnesses of infancy and childhood are caused by viruses of the Paramyxoviridae family, in particular measles virus, respiratory syncytial (RS) virus and parainfluenzavirus type 3 (PI3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3496981", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 460, "text": "Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30866768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "The large virus family Paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, Newcastle disease-, respiratory syncytial virus and metapneumoviruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22531181", "endSection": "abstract" } ] }, { "body": "Which disease is caused by de novo VPS4A mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33186545" ], "ideal_answer": [ "Mutations in the VPS4A gene, which encodes the alpha-subunit of the lysosomal sorting enzyme, beta-N-acetylhexosaminidase 4, are the cause of multisystem disease type 4 or Ferroportin disease.", "De novo mutations in the gene encoding for endosomal sorting enzyme VPS4A (Val4A) cause multisystem disease", "De \u03bdovo VPS4A mutations cause multisystem disease with abnormal neurodevelopment." ], "exact_answer": [ "Multisystem disease with abnormal neurodevelopment" ], "type": "factoid", "id": "601bde6e1cb411341a000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186545", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1312, "text": "The endosomal sorting complexes required for transport (ESCRTs) are essential for multiple membrane modeling and membrane-independent cellular processes. Here we describe six unrelated individuals with de novo missense variants affecting the ATPase domain of VPS4A, a critical enzyme regulating ESCRT function. Probands had structural brain abnormalities, severe neurodevelopmental delay, cataracts, growth impairment, and anemia. In cultured cells, overexpression of VPS4A mutants caused enlarged endosomal vacuoles resembling those induced by expression of known dominant-negative ATPase-defective forms of VPS4A. Proband-derived fibroblasts had enlarged endosomal structures with abnormal accumulation of the ESCRT protein IST1 on the limiting membrane. VPS4A function was also required for normal endosomal morphology and IST1 localization in iPSC-derived human neurons. Mutations affected other ESCRT-dependent cellular processes, including regulation of centrosome number, primary cilium morphology, nuclear membrane morphology, chromosome segregation, mitotic spindle formation, and cell cycle progression. We thus characterize a distinct multisystem disorder caused by mutations affecting VPS4A and demonstrate that its normal function is required for multiple human developmental and cellular processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186545", "endSection": "abstract" } ] }, { "body": "What is the target of a drug pidilizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26581237", "http://www.ncbi.nlm.nih.gov/pubmed/26394770", "http://www.ncbi.nlm.nih.gov/pubmed/29143272", "http://www.ncbi.nlm.nih.gov/pubmed/26513491", "http://www.ncbi.nlm.nih.gov/pubmed/24892254", "http://www.ncbi.nlm.nih.gov/pubmed/25965365", "http://www.ncbi.nlm.nih.gov/pubmed/25999597", "http://www.ncbi.nlm.nih.gov/pubmed/24771328", "http://www.ncbi.nlm.nih.gov/pubmed/26248256", "http://www.ncbi.nlm.nih.gov/pubmed/26647898", "http://www.ncbi.nlm.nih.gov/pubmed/24917416", "http://www.ncbi.nlm.nih.gov/pubmed/25056108", "http://www.ncbi.nlm.nih.gov/pubmed/24127452", "http://www.ncbi.nlm.nih.gov/pubmed/24332512" ], "ideal_answer": [ "Pidilizumab is a a humanised monoclonal antibody that targets programmed death-1 pathway." ], "exact_answer": [ "programmed death-1 pathway." ], "type": "factoid", "id": "5e3a6e70b5b409ea53000018", "snippets": [ { "offsetInBeginSection": 227, "offsetInEndSection": 365, "text": "We present results from the first study to evaluate the immune modulating antibody MDV9300 (pidilizumab) in pediatric patients with DIPG. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29143272", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 942, "text": "This has prompted multiple large ongoing phase III trials with the expectation for fast-track FDA approvals to satisfy unmet medical needs. Compounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24917416", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 937, "text": "Nivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25965365", "endSection": "abstract" }, { "offsetInBeginSection": 1248, "offsetInEndSection": 1528, "text": "Recent successes in early Phase I/II trials using anti-checkpoint inhibitor antibodies such as nivolumab or pidilizumab directed against PD-1 in the setting of Hodgkin's and non-Hodgkin's lymphomas validate the therapeutic utility of reversing B cell-mediated immune suppression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25999597", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 755, "text": "RECENT FINDINGS: Recent studies have evaluated the prevalence and prognostic implications of PD-1, PD-L1/2 expression in various lymphoma subtypes. We present an overview of the clinical trials evaluating pidilizumab, nivolumab, and pembrolizumab in patients with lymphoid malignancies, and highlight some of the more promising agents in this class, currently in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26248256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 471, "text": "BACKGROUND: This meta-analysis has been conducted to determine the risk of elevated transaminases associated with immune checkpoint inhibitors use in patients with cancer.METHODS: Studies eligible for our analysis included randomized Phase II and III trials of patients with cancer on ipilimumab, nivolumab, pembrolizumab, tremelimumab and pidilizumab, which describe events of elevated transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26394770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "AIM: We performed a meta-analysis of the risk of selected gastrointestinal toxicities associated with immune checkpoint inhibitors.PATIENTS & METHODS: Eligible studies included randomized trials of patients with solid tumors on ipilimumab, nivolumab, pembrolizumab, tremelimumab, pidilizumab and atezolizumab, describing events of diarrhea, vomiting or colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26513491", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 605, "text": "There are other perspective immune modulating agents, such as anti-PD\u200a1 antibodies (nivolumab, pembrolizumab, pidilizumab) and anti-PD\u200aL1 antibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647898", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 847, "text": "High levels of peripheral blood Tregs prior to therapy were associated with decreased progression-free survival in FL patients treated with either chemotherapy or combination immunotherapy that targeted CD20 and PD-1 with monoclonal antibodies rituximab and pidilizumab, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24771328", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 865, "text": "Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24892254", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 540, "text": "We did this phase 2 trial to investigate the activity of pidilizumab, a humanised anti-PD1 monoclonal antibody, with rituximab in patients with relapsed follicular lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24332512", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 220, "text": "Pidilizumab is an mAb that binds to PD-1 and is a safe and well-tolerated therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25056108", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 604, "text": "There are other perspective immune modulating agents, such as anti-PD\u200a1 antibodies (nivolumab, pembrolizumab, pidilizumab) and anti-PD\u200aL1 antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26647898", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 941, "text": "Compounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24917416", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 208, "text": "ignancies. Pidilizumab is an mAb that binds to PD-1 and is a safe and well-tolera", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25056108", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 953, "text": ", pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers. Long-term survi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25965365", "endSection": "abstract" }, { "offsetInBeginSection": 703, "offsetInEndSection": 864, "text": "Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24892254", "endSection": "abstract" } ] }, { "body": "List the proteins defining the triple negative breast cancer.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26387133", "http://www.ncbi.nlm.nih.gov/pubmed/29018573", "http://www.ncbi.nlm.nih.gov/pubmed/25506489" ], "ideal_answer": [ "The so called \"Triple Negative Breast Cancer\" (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene." ], "exact_answer": [ [ "oestrogen receptor" ], [ "progesterone receptor" ], [ "human epidermal growth factor receptor type 2" ] ], "type": "list", "id": "5e9206642d3121100d000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does not express the oestrogen and the progesterone receptors and the human epidermal growth factor receptor type 2 (HER2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29018573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "The so called \"Triple Negative Breast Cancer\" (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26387133", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 195, "text": "Triple negative breast cancers (TNBCs) are a diverse and heterogeneous group of tumors that by definition lack estrogen and progesterone receptors and amplification of the HER-2 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506489", "endSection": "abstract" } ] }, { "body": "Han Wistar and Sprague Dawley are breeds of what laboratory animal?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2756796", "http://www.ncbi.nlm.nih.gov/pubmed/15546683", "http://www.ncbi.nlm.nih.gov/pubmed/30476622", "http://www.ncbi.nlm.nih.gov/pubmed/24749500", "http://www.ncbi.nlm.nih.gov/pubmed/29097845", "http://www.ncbi.nlm.nih.gov/pubmed/22610983", "http://www.ncbi.nlm.nih.gov/pubmed/25537841", "http://www.ncbi.nlm.nih.gov/pubmed/23349040", "http://www.ncbi.nlm.nih.gov/pubmed/28068893", "http://www.ncbi.nlm.nih.gov/pubmed/32764845", "http://www.ncbi.nlm.nih.gov/pubmed/10321989", "http://www.ncbi.nlm.nih.gov/pubmed/22664268", "http://www.ncbi.nlm.nih.gov/pubmed/15764299", "http://www.ncbi.nlm.nih.gov/pubmed/32713280", "http://www.ncbi.nlm.nih.gov/pubmed/15533676", "http://www.ncbi.nlm.nih.gov/pubmed/24213005", "http://www.ncbi.nlm.nih.gov/pubmed/24213004", "http://www.ncbi.nlm.nih.gov/pubmed/11850967" ], "ideal_answer": [ "Han-Wistar and Sprague-Dawley rats", "Han Wistar and Sprague Dawley are breeds of Rats" ], "exact_answer": [ "rats" ], "type": "factoid", "id": "5e6d1c6f1af46fc130000021", "snippets": [ { "offsetInBeginSection": 80, "offsetInEndSection": 114, "text": "Wistar-Han and Sprague-Dawley rats", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30476622", "endSection": "title" }, { "offsetInBeginSection": 51, "offsetInEndSection": 86, "text": "Wistar Han and Sprague-Dawley Rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28068893", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28068893", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 116, "text": "Han-Wistar and Sprague-Dawley rats", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29097845", "endSection": "title" }, { "offsetInBeginSection": 133, "offsetInEndSection": 168, "text": "Han-Wistar and Sprague-Dawley rats ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29097845", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 451, "text": "Han-Wistar rats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29097845", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 694, "text": " Sprague-Dawley rats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29097845", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 751, "text": " Han-Wistar rats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29097845", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 682, "text": "Wistar-Han and SD rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30476622", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 442, "text": " to SD rats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30476622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "The Sprague Dawley (SD) and Han Wistar (HW) are the two most commonly used rat strains in Europe and the US, with the Han Wistar increasing in popularity because of its greater longevity and lower tumor burden.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32764845", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 367, "text": "The 600 MHz (1)H NMR spectra of urine were acquired as part of a series of drug toxicity studies from 450 control rat urine samples from each of two strains of laboratory rat (Han Wistar and Sprague Dawley).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15533676", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 522, "text": "The data from Wistar Han rats were compared with those from Sprague Dawley Crl:CD(SD) rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24213005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Differential performance of Wistar Han and Sprague Dawley rats in behavioral tests: differences in baseline behavior and reactivity to positive control agents.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664268", "endSection": "title" }, { "offsetInBeginSection": 113, "offsetInEndSection": 288, "text": "The present DNT study was conducted to generate historical data with the Wistar Han (WH) and Sprague Dawley (SD) rat strains, commonly used in Europe and the US, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22664268", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Comparison of longevity and common tumor profiles between Sprague-Dawley and Han Wistar rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32764845", "endSection": "title" }, { "offsetInBeginSection": 162, "offsetInEndSection": 384, "text": "The effects of rat strain and gender in in\u00a0vitro metabolism were investigated in Sprague Dawley (SD) and Wister Han (WH) rats based on the hepatocyte metabolic profiles of 14 small molecule drugs. Similarities were found b", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32713280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in general toxicity studies--comparative data to Sprague Dawley rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24213005", "endSection": "title" }, { "offsetInBeginSection": 352, "offsetInEndSection": 428, "text": "ference ranges were generated for male Sprague Dawley and Han Wistar rats.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349040", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1277, "text": "The resulting Wistar Han rat predictive models were then used to predict PP in a test group of Sprague Dawley rats following administration of fenofibrate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15764299", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1276, "text": "e and the melatonin-related parameters expressed per pineal were used to assess the melatonin-synthesizing capacity of the pineal glands, it was found that the outbred Wistar and Sprague-Dawley rats and the inbred LEWIS-derived (LEW/Han) rats, all of which were albinos, had the most active pineals. Intermediate activ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2756796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28068893", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source, diet, and housing conditions, as well as the incidences of nonneoplastic lesions and neoplasms observed in different laboratories.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28068893", "endSection": "abstract" }, { "offsetInBeginSection": 2256, "offsetInEndSection": 2442, "text": "For the parameters evaluated, the Wistar Hannover rat had greater variability and an increased incidence of spontaneous malformations as compared to the Crl:CD (SD)BR Sprague-Dawley rat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in embryo-fetal development studies--comparative data to Sprague Dawley rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24213004", "endSection": "title" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1049, "text": "However, the EROD activity of Wistar rats and the MROD activity of Sprague Dawley rats were higher in males than females.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22610983", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1264, "text": "Tumor drift was not common but occurred far more often in outbred rat strains (Wistar and Sprague-Dawley) than in the inbred rat strain (F344).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15546683", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 686, "text": "Therefore, the aim of this study was to compare the play behavior of three other strains of laboratory rats (e.g., Wistar, Sprague-Dawley, and Brown Norway).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24749500", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 535, "text": "The aim of the present study was to compare the variation in allothetic visuospatial learning in most commonly used laboratory rat strains: inbred Wistar (W) and Sprague-Dawley (SD), outcrossed Wistar/Sprague-Dawley (W/SD), and outbred Long Evans (LE) rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25537841", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 718, "text": "Differences in shape of the lateral semicircular duct exist between the two breeds and the cupular mechanical sensitivity is significantly higher in Wistar than in Sprague-Dawley rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10321989", "endSection": "abstract" } ] }, { "body": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12899756", "http://www.ncbi.nlm.nih.gov/pubmed/27823966", "http://www.ncbi.nlm.nih.gov/pubmed/12777642" ], "ideal_answer": [ "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor (RHG).", "IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE. IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins, thus being involved in the pathogenesis of SLE.", "IFIT1 is a newly discovered systemic lupus erythematosus related up-regulated gene. IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins.", "The IFIT1 gene, encoding the syntaxin binding protein 1, is highly expressed in Systemic Lupus Erythematosis (SLE) and its expression is downregulated significantly in cases of SLE. Loss of IFit1 expression is correlated with SLE disease activity and leads to activation of transcriptional mediator Gli2, with consequent inhibition of I\u03baB kinase activity, resulting in dysfunction of myeloid cell growth and transformation to a malignant state.IFIT1 (interferon regulatory factor 1) is an interferon-binding protein that", "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factors.", "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor (RHC).", "The IFIT1 gene, originally identified as a telomere-binding factor in yeast, is now recognized to play a critical role in the pathogenesis of Systemic Lupus Erythematosus (SLE) disease. IFit1 overexpression generates an inflammatory response via activation of transcriptional mediator NF-kappaB and leads to activation of the nuclear factor \u03baB signaling pathway, with consequent inhibition of I\u03baB kinase and nuclear factor-\u03baB activation.", "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor (RH/RAC).", "IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor . IfIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE . Ifit1 may regulate the activation of Rho and Rac proteins, thus being involved in the pathogenesis of the disease .", "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor." ], "type": "summary", "id": "5fdb4364a43ad31278000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Renal damage is the major cause of SLE associated mortality, and IFIT1expression was elevated in SLE cases in accordance of previous studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27823966", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 239, "text": "To investigate the protein-to-protein interaction of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), a newly discovered systemic lupus erythematosus (SLE) related up-regulated gene, and its possible function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12899756", "endSection": "abstract" }, { "offsetInBeginSection": 1482, "offsetInEndSection": 1646, "text": "IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins, thus being involved in the pathogenesis of SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12899756", "endSection": "abstract" }, { "offsetInBeginSection": 1619, "offsetInEndSection": 1742, "text": "An IFIT1 protein- protein interaction study showed that IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777642", "endSection": "abstract" }, { "offsetInBeginSection": 2008, "offsetInEndSection": 2303, "text": "IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777642", "endSection": "abstract" }, { "offsetInBeginSection": 2014, "offsetInEndSection": 2189, "text": "is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777642", "endSection": "abstract" }, { "offsetInBeginSection": 2011, "offsetInEndSection": 2150, "text": "T1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac gu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777642", "endSection": "abstract" } ] }, { "body": "Has tocilizumab been assessed against Covid-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33262810" ], "ideal_answer": [ "Preliminary clinical results have indicated that tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile." ], "exact_answer": "yes", "type": "yesno", "id": "60258ebe1cb411341a0000a8", "snippets": [ { "offsetInBeginSection": 398, "offsetInEndSection": 673, "text": "Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33262810", "endSection": "abstract" } ] }, { "body": "Variants in which genes cause nonsyndromic retinal degeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32753734", "http://www.ncbi.nlm.nih.gov/pubmed/24697911", "http://www.ncbi.nlm.nih.gov/pubmed/28460050", "http://www.ncbi.nlm.nih.gov/pubmed/25649381" ], "ideal_answer": [ "Variants in DYNC2H1, IFT81, USH2A and ABHD12 can cause nonsyndromic retinal degeneration." ], "exact_answer": [ [ "DYNC2H1" ], [ "IFT81" ], [ "USH2A" ], [ "ABHD12" ] ], "type": "list", "id": "601c18eb1cb411341a000010", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753734", "endSection": "title" }, { "offsetInBeginSection": 398, "offsetInEndSection": 1438, "text": "Four novel DYNC2H1 variants (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) and one previously reported variant (V5, g.103339363T>G) were identified. In proband 1 (V1/V2), V1 was predicted to introduce a premature termination codon (PTC), whereas V2 disrupted the exon 41 splice donor site causing incomplete skipping of exon 41. V1 and V2 impaired dynein-2 motility in vitro and perturbed IFT88 distribution within cilia. V3, homozygous in probands 2-4, is predicted to cause a PTC in a retina-predominant transcript. Analysis of retinal organoids showed that this new transcript expression increased with organoid differentiation. V4, a novel missense variant, was in trans with V5, previously associated with Jeune asphyxiating thoracic dystrophy (JATD).CONCLUSION: The DYNC2H1 variants discussed herein were either hypomorphic or affecting a retina-predominant transcript and caused nonsyndromic IRD. Dynein variants, specifically DYNC2H1 variants are reported as a cause of non syndromic IRD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "IFT81 as a Candidate Gene for Nonsyndromic Retinal Degeneration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28460050", "endSection": "title" }, { "offsetInBeginSection": 804, "offsetInEndSection": 1795, "text": "Compound heterozygous mutations in IFT81, including one nonsense (c.1213C>T, p.R405*) and one missense variant (c.1841T>C, p.L614P), were identified in a nonsyndromic CRD proband. Extensive functional analyses of the missense variant in cell culture and zebrafish strongly suggests its pathogenic nature. Loss of IFT81 impairs ciliogenesis and, interestingly, the missense variant displayed significantly reduced rescue of ciliogenesis in the IFT81 knockdown in vitro system. Consistently, dramatic reduction of rescue efficiency of the ift81 mutant zebrafish embryo by mRNA with the missense variant was observed, further supporting its pathogenicity.Conclusions: Consistent with the function of the IFT-B complex in the maintenance of photoreceptor cilium, we report a case of mutations in a core IFT-B protein, IFT81. This represents the first report of mutations in IFT81 as a candidate gene for nonsyndromic retinal dystrophy, hence expanding the phenotype spectrum of IFT-B components.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28460050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1912, "text": "Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276\u2009G>T, p.(Cys759Phe) mutation and five additional variants: c.2802\u2009T>G, p.(Cys934Trp); c.10073\u2009G>A, p.(Cys3358Tyr); c.11156\u2009G>A, p.(Arg3719His); c.12295-3\u2009T>A; and c.12575\u2009G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25649381", "endSection": "abstract" }, { "offsetInBeginSection": 1883, "offsetInEndSection": 2370, "text": "Null mutations in the ABHD12 gene lead to PHARC syndrome, a neurodegenerative disease including polyneuropathy, hearing loss, cerebellar ataxia, RP, and early-onset cataract. Our study allowed us to\u00a0report 5 new mutations in ABHD12. This is the first time missense mutations have been described for this gene. Furthermore, these findings are expanding the spectrum of phenotypes associated with ABHD12 mutations ranging from PHARC syndrome to a nonsyndromic form of retinal degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24697911", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of Omecamtiv Mecarbil.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21415352", "http://www.ncbi.nlm.nih.gov/pubmed/33165138", "http://www.ncbi.nlm.nih.gov/pubmed/33176437", "http://www.ncbi.nlm.nih.gov/pubmed/32969560", "http://www.ncbi.nlm.nih.gov/pubmed/26140433", "http://www.ncbi.nlm.nih.gov/pubmed/26587768", "http://www.ncbi.nlm.nih.gov/pubmed/31103235", "http://www.ncbi.nlm.nih.gov/pubmed/32035892", "http://www.ncbi.nlm.nih.gov/pubmed/33185990", "http://www.ncbi.nlm.nih.gov/pubmed/31267148", "http://www.ncbi.nlm.nih.gov/pubmed/27322915", "http://www.ncbi.nlm.nih.gov/pubmed/29707029", "http://www.ncbi.nlm.nih.gov/pubmed/26709596", "http://www.ncbi.nlm.nih.gov/pubmed/21856481", "http://www.ncbi.nlm.nih.gov/pubmed/21856480", "http://www.ncbi.nlm.nih.gov/pubmed/29792814", "http://www.ncbi.nlm.nih.gov/pubmed/29278207", "http://www.ncbi.nlm.nih.gov/pubmed/26065842", "http://www.ncbi.nlm.nih.gov/pubmed/32636378", "http://www.ncbi.nlm.nih.gov/pubmed/26025342", "http://www.ncbi.nlm.nih.gov/pubmed/28082673", "http://www.ncbi.nlm.nih.gov/pubmed/28775348", "http://www.ncbi.nlm.nih.gov/pubmed/32513536", "http://www.ncbi.nlm.nih.gov/pubmed/25680381" ], "ideal_answer": [ "Omecamtiv mecarbil is a novel, selective cardiac myosin activator that has been shown to improve cardiac function and to decrease ventricular volumes, heart rate, and N-terminal pro-B-type natriuretic peptide in patients with heart failure." ], "type": "summary", "id": "601c13be1cb411341a00000d", "snippets": [ { "offsetInBeginSection": 299, "offsetInEndSection": 536, "text": "Omecamtiv mecarbil is a novel, selective cardiac myosin activator that has been shown to improve cardiac function and to decrease ventricular volumes, heart rate, and N-terminal pro-B-type natriuretic peptide in patients with chronic HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32035892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Omecamtiv mecarbil (OM), an activator of cardiac myosin, strongly affects contractile characteristics of the ventricles and, to a much lesser extent, the characteristics of atrial contraction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32513536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Omecamtiv mecarbil (OM) is a putative positive inotropic tool for treatment of systolic heart dysfunction, based on the finding that in vivo it increases the ejection fraction and in vitro it prolongs the actin-bond life time of the cardiac and slow-skeletal muscle isoforms of myosin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32636378", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 723, "text": "Two novel cardiac myotropes, omecamtiv mecarbil and danicamtiv, target cardiac myosin to increase left ventricular systolic performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33165138", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 258, "text": "Omecamtiv mecarbil, a novel activator of cardiac myosin, improves left ventricular systolic function and remodeling and reduces natriuretic peptides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33176437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33185990", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33185990", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1066, "text": "The mechanism of action of omecamtiv mecarbil also provides insights into uncovering how force is generated by molecular motors.Omecamtiv mecarbil (OM) is a cardiac myosin activator that is currently in clinical trials for heart failure treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28775348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Omecamtiv mecarbil is a selective, small-molecule activator of cardiac myosin that is being developed as a potential treatment for heart failure with reduced ejection fraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28775348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "The myosin activator omecamtiv mecarbil: a promising new inotropic agent.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27322915", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "A novel myosin activator, omecamtiv mecarbil (OM), is a cardiac inotropic agent with a unique new mechanism of action, which is thought to arise from an increase in the transition rate of myosin into the actin-bound force-generating state without increasing calcium (Ca2+) transient. There remains, howeve", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31267148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "The energy-saving effect of a new myosin activator, omecamtiv mecarbil, on LV mechanoenergetics in rat hearts with blood-perfused isovolumic contraction model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31267148", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Omecamtiv mecarbil (OM) is a selective cardiac myosin activator (myotrope), currently in Phase 3 clinical investigation as a novel treatment for heart failure with reduced ejection fraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32969560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28775348", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "OBJECTIVE: Omecamtiv mecarbil is a novel small molecule that directly activates cardiac myosin and increases cardiac contractility without increasing cardiac myocyte intracellu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26709596", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1066, "text": "Omecamtiv mecarbil (OM) is a cardiac myosin activator that is currently in clinical trials for heart failure treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28775348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "A novel myosin activator, omecamtiv mecarbil (OM), is a cardiac inotropic agent with a unique new mechanism of action, which is thought to arise from an increase in the transition rate of myosin into the actin-bound force-generating state without increasing calcium (Ca2+) transient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31267148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "OBJECTIVE: Omecamtiv mecarbil is a novel small molecule that directly activates cardiac myosin and increases cardiac contractility without increasing cardiac myocyte intracellul", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26709596", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 342, "text": "Omecamtiv mecarbil (OM) is a compound that has been developed to treat systolic heart failure via targeting the cardiac myosin heavy chain to increase myocardial contractility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31103235", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 436, "text": "Omecamtiv mecarbil is a first-in-class cardiac myosin activator, which increases the proportion of myosin heads that are tightly bound to actin and creates a force-producing state that is not associated with cytosolic calcium accumulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29707029", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 375, "text": "nd mortality. A novel selective cardiac myosin activator, omecamtiv mecarbil (CK-1827452/ AMG-423) is a small molecule that activates the sarcomere proteins directly, resulting in prolonged systolic ejection time and increased cardiac ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26587768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The novel cardiac myosin activator omecamtiv mecarbil increases the calcium sensitivity of force production in isolated cardiomyocytes and skeletal muscle fibres of the rat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26140433", "endSection": "title" }, { "offsetInBeginSection": 201, "offsetInEndSection": 343, "text": "This study tested the hypothesis that omecamtiv mecarbil, a selective cardiac myosin activator, will augment cardiac function in human beings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The small molecule drug omecamtiv mecarbil (OM) specifically targets cardiac muscle myosin and is known to enhance cardiac muscle performance, yet its impact on human cardiac myosin motor function is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28082673", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Omecamtiv Mecarbil: A Myosin Motor Activator Agent with Promising Clinical Performance and New in vitro Results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29278207", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Omecamtiv mecarbil: a new cardiac myosin activator for the treatment of heart failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26587768", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Omecamtiv Mecarbil, a Cardiac Myosin Activator, Increases Ca2+ Sensitivity in Myofilaments With a Dilated Cardiomyopathy Mutant Tropomyosin E54K.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26065842", "endSection": "title" }, { "offsetInBeginSection": 63, "offsetInEndSection": 344, "text": "A novel class of agents, the myosin motor activators, acts directly on cardiac myosin resulting in an increased force generation and prolongation of contraction. Omecamtiv mecarbil, the lead molecule of this group, is now in human phase 3 displaying promising clinical performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29792814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "We determined the effect of Omecamtiv Mecarbil, a novel allosteric effector of cardiac muscle myosin, on the kinetic and \"in vitro\" motility properties of the porcine ventricular heavy meromyosin (PV-HMM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856481", "endSection": "title" }, { "offsetInBeginSection": 317, "offsetInEndSection": 436, "text": "We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856481", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 350, "text": "To avoid these limitations, we previously developed omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26025342", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "BACKGROUND: Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26025342", "endSection": "abstract" } ] }, { "body": "List the types of defensins expressed in humans.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30121363", "http://www.ncbi.nlm.nih.gov/pubmed/28423004", "http://www.ncbi.nlm.nih.gov/pubmed/29310427" ], "ideal_answer": [ "Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express \u03b1- and \u03b2-defensins, which are known for their antiviral and antibacterial activities." ], "exact_answer": [ [ "\u03b1-defensins" ], [ "\u03b2-defensins" ] ], "type": "list", "id": "5e9208702d3121100d000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 24, "text": "Human \u03b1 and \u03b2-defensins ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28423004", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1275, "text": "the data indicate that the human \u03b2-defensin family is a novel group of potassium channel inhibitors with diverse types of human \u03b2-defensin-potassium channel interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30121363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express \u03b1- and \u03b2-defensins, which are known for their antiviral and antibacterial activities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29310427", "endSection": "abstract" } ] }, { "body": "What do HA and NA stand for with respect to the flue virus, e.g. H1N1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24027333", "http://www.ncbi.nlm.nih.gov/pubmed/30967460", "http://www.ncbi.nlm.nih.gov/pubmed/15925433", "http://www.ncbi.nlm.nih.gov/pubmed/23349854", "http://www.ncbi.nlm.nih.gov/pubmed/29699789", "http://www.ncbi.nlm.nih.gov/pubmed/25609803", "http://www.ncbi.nlm.nih.gov/pubmed/2300562", "http://www.ncbi.nlm.nih.gov/pubmed/10067670", "http://www.ncbi.nlm.nih.gov/pubmed/23125526", "http://www.ncbi.nlm.nih.gov/pubmed/29625056", "http://www.ncbi.nlm.nih.gov/pubmed/25751873", "http://www.ncbi.nlm.nih.gov/pubmed/29167344", "http://www.ncbi.nlm.nih.gov/pubmed/29113775", "http://www.ncbi.nlm.nih.gov/pubmed/33065852", "http://www.ncbi.nlm.nih.gov/pubmed/32362450", "http://www.ncbi.nlm.nih.gov/pubmed/28141594", "http://www.ncbi.nlm.nih.gov/pubmed/12443663", "http://www.ncbi.nlm.nih.gov/pubmed/32825107" ], "ideal_answer": [ "VaxArray assays for influenza hemagglutinin (HA) and neuraminidase (NA) have been developed to address this need.", "HA and NA stand for hemagglutinin (HA) and neuraminidase (NA), two components of the flue virus genome.", "HA and NA, (sometimes H or N) refer to influenza surface proteins neuraminidase (NA) and hemagglutinin (HA)." ], "type": "summary", "id": "5e722812c6a8763d2300000a", "snippets": [ { "offsetInBeginSection": 247, "offsetInEndSection": 266, "text": "neuraminidase (NA) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Genetic variation of influenza neuraminidase (NA), unlike for hemagglutinin (HA), has not been fully characterized. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29113775", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 265, "text": "VaxArray assays for influenza hemagglutinin (HA) and neuraminidase (NA) have been developed to address this need. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29699789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Antibody (Ab) responses and protection against influenza virus infection in mice immunized intranasally with hemagglutinin (HA) or neuraminidase (NA) purified from the A/Beijing/262/95 (A/Beijing) (H1N1) virus were compared among B10 congenic mouse strains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12443663", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 407, "text": "Since antibodies against HA and neuraminidase (NA) contribute independently to protection against disease, antigenic changes in NA may allow A(H1N1)pdm09 viruses to escape from vaccine-induced immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30967460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "The ability of plasmid DNA encoding hemagglutinin (HA), neuraminidase (NA) or matrix protein (M1) from influenza virus A/PR/8/34 (PR8) (H1N1), and mixtures of these plasmid DNAs (HA + NA and HA + NA + M1) to protect against homologous or heterologous virus infection was examined in BALB/c mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10067670", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 537, "text": "ODS: Alignments were made with H1N1 hemagglutinin and neuraminidase (HA and NA, respectively) sequences; only conserved sites were used for antigenicity prediction. Two", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32362450", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 522, "text": "LTS: In this report, 72 hemagglutinin (HA) and 45 neuraminidase (NA) H1N1 virus gene sequences, isolated in 2009 from various regions of Saudi Arabia, were analyzed. Gen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28141594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Two surface glycoproteins of influenza virus, haemagglutinin (HA) and neuraminidase (NA), play opposite roles in terms of their interaction with host sialic acid receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Hemagglutinin (HA) and neuraminidase (NA) are major glycoproteins expressed on the surface of influenza virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33065852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "UNLABELLED: In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in vi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25609803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "The hemagglutinin (HA) and neuraminidase (NA) external glycoprotein antigens of H1N1 and H3N2 subtypes of epidemiologically important influenza A viruses prevalent during recent decades were subjected to intensive antigenic analysis by four different methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2300562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24027333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The ability of a single dose of plasmid DNA encoding neuraminidase (NA) or hemagglutinin (HA) from influenza virus A/PR/8/34 (PR8) (H1N1) to protect against homologous virus infection was examined in BALB/c mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15925433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of\u00a0protection against influenza virus infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625056", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 338, "text": "Previous studies have suggested that Cal-derived chimeric hemagglutinin (HA) and neuraminidase (NA) improve virus yields.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32825107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Influenza type A viruses are classified into subtypes based on their two surface proteins, hemagglutinin (HA) and neuraminidase (NA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25751873", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 518, "text": "There are two glycoproteins in this lipid membrane; namely, hemagglutinin (HA) which helps in attachment of the viral strain on the host cell surface and neuraminidase (NA) that is responsible for initiation of viral infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23125526", "endSection": "abstract" } ] }, { "body": "Is the TFR1 gene dispensable for erythropoiesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23416069", "http://www.ncbi.nlm.nih.gov/pubmed/25767952", "http://www.ncbi.nlm.nih.gov/pubmed/31601687", "http://www.ncbi.nlm.nih.gov/pubmed/30108502", "http://www.ncbi.nlm.nih.gov/pubmed/30093529", "http://www.ncbi.nlm.nih.gov/pubmed/18316026", "http://www.ncbi.nlm.nih.gov/pubmed/28151426", "http://www.ncbi.nlm.nih.gov/pubmed/16755567", "http://www.ncbi.nlm.nih.gov/pubmed/17119325", "http://www.ncbi.nlm.nih.gov/pubmed/27498743", "http://www.ncbi.nlm.nih.gov/pubmed/30232412" ], "ideal_answer": [ "Yes. The TFR1 gene is a key part of the mechanism by which the body delivers iron to the red blood cells. It is not dispensable for erythropoiesis.", "No, the TFR1 gene, which encodes the triggering receptor encoded in myeloid cells of the erythropoietin receptor 1 (TFR1), is an essential regulator of hematopoietic stem and progenitor cells that is defective in several forms of myeloma.", "No, the TFR1 gene, due to the presence of two promoters (Tf1 and Tf2) in its 5' flanking region, is required for erythropoiesis.", "Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis.", "Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake.", "No, the TFR1 gene, due to the presence of two promoters (TFR1 and TFR2) in its 5' flanking region, is required for erythropoiesis but not for granulocytopenia." ], "exact_answer": "no", "type": "yesno", "id": "5fdb2e60a43ad3127800000c", "snippets": [ { "offsetInBeginSection": 908, "offsetInEndSection": 1121, "text": "These studies describe how point mutations of the transferrin receptor can cause a microcytic anemia that does not respond to iron therapy and would not be detected by routine iron studies, such as serum ferritin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30093529", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1292, "text": "Ret-He was the only red cell marker affected prior to the onset of brain ID. The clinical practice of using anemia as the preferred biomarker for diagnosis of iron deficiency may need reconsidering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30232412", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1342, "text": "The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30108502", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 411, "text": "Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28151426", "endSection": "abstract" }, { "offsetInBeginSection": 1687, "offsetInEndSection": 2056, "text": "aken together, decreasing TfR1 expression during \u03b2-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in \u03b2-thalassemic mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28151426", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 150, "text": "The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25767952", "endSection": "abstract" }, { "offsetInBeginSection": 1132, "offsetInEndSection": 1343, "text": "The signaling functions of both TfR1 and TfR2 in erythroid cells were unexpected and these recent findings open a new field of research regarding the last steps of erythroid differentiation and their regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25767952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498743", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 545, "text": " In humans, hematopoietic erythroid precursor cells express high levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27498743", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1162, "text": "We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16755567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Soluble transferrin receptor-1 (sTfR1) concentrations are increased in the plasma under two conditions that are associated with increased iron absorption, i.e. iron deficiency and increased erythropoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18316026", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 376, "text": "Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23416069", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1122, "text": "These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31601687", "endSection": "abstract" } ] }, { "body": "Which are the predominant rotavirus genotypes around the world?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25224179", "http://www.ncbi.nlm.nih.gov/pubmed/30156344" ], "ideal_answer": [ "The predominant RV genotypes circulating all over the world are G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8], while G12[P6] and G12[P8] are emerging genotypes." ], "exact_answer": [ [ "G1P[8]" ], [ "G2P[4]" ], [ "G3P[8]" ], [ "G4P[8]" ], [ "G9P[8]" ] ], "type": "list", "id": "5e76611b835f4e4777000002", "snippets": [ { "offsetInBeginSection": 928, "offsetInEndSection": 1086, "text": "The predominant RV genotypes circulating all over the world are G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8], while G12[P6] and G12[P8] are emerging genotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156344", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1085, "text": "The predominant RV genotypes circulating all over the world are G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8], while G12[P6] and G12[P8] are emerging genotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Comprehensive reviews of pre licensure rotavirus strain prevalence data indicated the global importance of six rotavirus genotypes, G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25224179", "endSection": "abstract" } ] }, { "body": "Which TREX mRNA export complex subunits have been implicated in neurodevelopmental disorders?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32116545" ], "ideal_answer": [ "Multiple TREX mRNA export complex subunits, e.g. THOC1, THOC2, THOC5, THOC6, THOC7, have been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer.", "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in NDD's.", "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have also been implicated.", "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in NDDs.", "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in NDDs and cancer, respectively.", "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in cancer." ], "exact_answer": [ [ "THOC1" ], [ "THOC2" ], [ "THOC5" ], [ "THOC6" ], [ "THOC7" ] ], "type": "list", "id": "601d31df1cb411341a00002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1400, "text": "Multiple TREX mRNA export complex subunits (e.g., THOC1, THOC2, THOC5, THOC6, THOC7) have now been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer. We previously implicated missense and splicing-defective THOC2 variants in NDDs and a broad range of other clinical features. Here we report 10 individuals from nine families with rare missense THOC2 variants including the first case of a recurrent variant (p.Arg77Cys), and an additional individual with an intragenic THOC2 microdeletion (Del-Ex37-38). Ex vivo missense variant testing and patient-derived cell line data from current and published studies show 9 of the 14 missense THOC2 variants result in reduced protein stability. The splicing-defective and deletion variants result in a loss of small regions of the C-terminal THOC2 RNA binding domain (RBD). Interestingly, reduced stability of THOC2 variant proteins has a flow-on effect on the stability of the multi-protein TREX complex; specifically on the other NDD-associated THOC subunits. Our current, expanded cohort refines the core phenotype of THOC2 NDDs to language disorder and/or ID, with a variable severity, and disorders of growth. A subset of affected individuals' has severe-profound ID, persistent hypotonia and respiratory abnormalities. Further investigations to elucidate the pathophysiological basis for this severe phenotype are warranted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32116545", "endSection": "abstract" } ] }, { "body": "What is the use of the Liverpool Elbow Score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17169590", "http://www.ncbi.nlm.nih.gov/pubmed/21813443", "http://www.ncbi.nlm.nih.gov/pubmed/25105787", "http://www.ncbi.nlm.nih.gov/pubmed/28601487", "http://www.ncbi.nlm.nih.gov/pubmed/30126385", "http://www.ncbi.nlm.nih.gov/pubmed/23312819", "http://www.ncbi.nlm.nih.gov/pubmed/25441571", "http://www.ncbi.nlm.nih.gov/pubmed/23325975", "http://www.ncbi.nlm.nih.gov/pubmed/33069940", "http://www.ncbi.nlm.nih.gov/pubmed/23456483", "http://www.ncbi.nlm.nih.gov/pubmed/19373479", "http://www.ncbi.nlm.nih.gov/pubmed/20427841", "http://www.ncbi.nlm.nih.gov/pubmed/19380130" ], "ideal_answer": [ "The Liverpool Elbow Score (LES) is a newly developed, validated elbow-specific score. It has been widely used to assess the outcomes of total elbow replacement in various conditions." ], "type": "summary", "id": "5e4752933f54159529000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "BACKGROUND: The Liverpool Elbow Score (LES) has been widely used to assess the outcomes of total elbow replacement in various conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30126385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Validation of the Liverpool Elbow Score for evaluation of elbow stiffness.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30126385", "endSection": "title" }, { "offsetInBeginSection": 1358, "offsetInEndSection": 1574, "text": "CONCLUSION: Our results suggest that the LES is a valid elbow-specific scoring system that can be used to evaluate joint function in patients with elbow stiffness, though some items included had some weakness either.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30126385", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 725, "text": "Outcome scores included the Mayo Elbow Performance Score, the Liverpool Elbow Score, and the 12-Item Short Form Health Survey (version 1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28601487", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 824, "text": "Outcome was assessed by means of the Liverpool Elbow Score, pain experience, patient satisfaction, range of motion, and radiographic imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25441571", "endSection": "abstract" }, { "offsetInBeginSection": 1885, "offsetInEndSection": 1992, "text": "The functional outcome was assessed using the Constant-Murley (CM) and Liverpool Elbow Score (LES) systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Responsiveness of the Liverpool Elbow Score in elbow arthroplasty.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312819", "endSection": "title" }, { "offsetInBeginSection": 284, "offsetInEndSection": 432, "text": "The aim of this prospective observational study was to assess these parameters for the Liverpool Elbow Score (LES) in total elbow replacement (TER).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23312819", "endSection": "abstract" }, { "offsetInBeginSection": 743, "offsetInEndSection": 848, "text": "At final evaluation, union (radiologically) and elbow function (Liverpool Elbow Score, LES) was assessed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23325975", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 881, "text": "Evaluation using a pain visual analog scale (VAS) and Liverpool elbow score was performed at 6 weeks, 3 months, and 6 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21813443", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 862, "text": "The patient-answered questionnaire (PAQ) portion of the Liverpool Elbow Score (LES) was evaluated 2 to 37 months later by telephone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20427841", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 450, "text": "PATIENTS: Forty-five patients with 54 replaced elbows, with an average age of 69 (range 49-84) were clinically [using Mayo Clinical Performance Index (MCPI) and Liverpool Elbow Score (LES)] and radiographically assessed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19373479", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 975, "text": "Follow up involved assessment of functional outcome using the Mayo Elbow Performance Score (MEPS) and Liverpool Elbow Score (LES), reduction results and complication rates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19380130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Use of the Liverpool Elbow Score as a postal questionnaire for the assessment of outcome after total elbow arthroplasty.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17169590", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The Liverpool Elbow Score (LES) is a newly developed, validated elbow-specific score. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17169590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The Liverpool Elbow Score (LES) is a newly developed, validated elbow-specific score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17169590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "BACKGROUND: The Liverpool Elbow Score (LES) has been widely used to assess the outcomes of total elbow replacement in various conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30126385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "BACKGROUND: The Liverpool Elbow Score (LES) has been widely used to assess the outcomes of total elbow replacement in various ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30126385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The Liverpool Elbow Score (LES) is a newly developed, validated elbow-specific score. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17169590", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 248, "text": "ncreasing. Liverpool Elbow Scale (LES) is an elbow-specific outcome score that provides a comprehensive assessment of by both the clinicians and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33069940", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 137, "text": "The Liverpool Elbow Score (LES) has been widely used to assess the outcomes of total elbow replacement in various conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30126385", "endSection": "abstract" } ] }, { "body": "Is Bcl-2-like protein 1 an pro apoptotic protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28521469", "http://www.ncbi.nlm.nih.gov/pubmed/26045046", "http://www.ncbi.nlm.nih.gov/pubmed/29846950", "http://www.ncbi.nlm.nih.gov/pubmed/24837143" ], "ideal_answer": [ "No,\nit is an anti-apoptotic protein." ], "exact_answer": "no", "type": "yesno", "id": "5e94aadf0d431b5f73000002", "snippets": [ { "offsetInBeginSection": 93, "offsetInEndSection": 289, "text": "Extensively established key effectors of such apoptotic bypass mechanisms, the antiapoptotic BCL-2 (apoptosis regulator BCL-2) proteins, determine the response of cancer cells to chemotherapeutics", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29846950", "endSection": "abstract" }, { "offsetInBeginSection": 1143, "offsetInEndSection": 1270, "text": "decreasing the expression of anti-apoptotic factors, including apoptosis regulator Bcl-2 and Bcl-2-like protein 1 in FaDu cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28521469", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 472, "text": "Like many cancers, TNBC cells often deregulate programmed cell death by upregulating anti-apoptotic proteins of the B-cell CLL/lymphoma 2 (Bcl-2) family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26045046", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1176, "text": " anti-apoptotic Bcl-2-like protein 1 (BCL2L1, Bcl-xL) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24837143", "endSection": "abstract" } ] }, { "body": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29898626" ], "ideal_answer": [ "Yes, there is evidence that glucoraphanin from broccoli can help reduce obesity.", "Yes, glucoraphanin from vegetables can help reduce obesity.", "Glucoraphanin: a broccoli sprout extract can ameliorate obesity-induced inflammation and insulin resistance", "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance.", "Yes, Glucoraphanin from vegetables can help reduce obesity.", "Yes, it has been documented that glucoraphanin from broccoli can reduce obesity." ], "exact_answer": "yes", "type": "yesno", "id": "5e52c96b6d0a27794100004f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29898626", "endSection": "title" }, { "offsetInBeginSection": 684, "offsetInEndSection": 1001, "text": "A recent study demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29898626", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1128, "text": "Thus, this review focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29898626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29898626", "endSection": "title" }, { "offsetInBeginSection": 694, "offsetInEndSection": 1013, "text": "tudy demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia. Thus, this ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29898626", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1144, "text": "iew focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD. Abbreviations: ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29898626", "endSection": "abstract" } ] }, { "body": "What is the function of the zelda transcription factor in D. melanogaster?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20599892", "http://www.ncbi.nlm.nih.gov/pubmed/22537497", "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "http://www.ncbi.nlm.nih.gov/pubmed/28676122", "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "http://www.ncbi.nlm.nih.gov/pubmed/26335633", "http://www.ncbi.nlm.nih.gov/pubmed/30518940", "http://www.ncbi.nlm.nih.gov/pubmed/22028662", "http://www.ncbi.nlm.nih.gov/pubmed/30993896", "http://www.ncbi.nlm.nih.gov/pubmed/20102629", "http://www.ncbi.nlm.nih.gov/pubmed/22028675", "http://www.ncbi.nlm.nih.gov/pubmed/29261646", "http://www.ncbi.nlm.nih.gov/pubmed/23891688", "http://www.ncbi.nlm.nih.gov/pubmed/25538246", "http://www.ncbi.nlm.nih.gov/pubmed/30982648", "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "http://www.ncbi.nlm.nih.gov/pubmed/18931655" ], "ideal_answer": [ "The zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility." ], "type": "summary", "id": "5fdb2e91a43ad3127800000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18931655", "endSection": "title" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1191, "text": "Here we report that the zinc-finger protein Zelda (Zld; Zinc-finger early Drosophila activator) binds specifically to these sites and is capable of activating transcription in transient transfection assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18931655", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1062, "text": "We demonstrated that Grh and the previously characterized transcriptional activator Zelda (Zld) bind to different TAGteam sequences with varying affinities, and that Grh competes with Zld for TAGteam occupancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20599892", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 475, "text": "Recently the discovery of the transcriptional activator Zelda (Zld), which binds to CAGGTAG and related sequences present in the enhancers of many early-activated genes in Drosophila, hinted at a mechanism for how batteries of genes could be simultaneously activated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028675", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 534, "text": "In Drosophila, the MZT is preceded by the transcription of a small number of genes that initiate sex determination, patterning, and other early developmental processes; and the zinc-finger protein Zelda (ZLD) plays a key role in their transcriptional activation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22028662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The Drosophila Zelda transcription factor plays an important role in regulating transcription at the embryonic maternal-to-zygotic transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22537497", "endSection": "abstract" }, { "offsetInBeginSection": 2108, "offsetInEndSection": 2280, "text": "n summary, Zelda collaborates with bHLH-PAS proteins to directly regulate midline and tracheal expression of an evolutionary dynamic enhancer in the post-blastoderm embryo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22537497", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 650, "text": "We demonstrate that increasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30518940", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1103, "text": "We propose that Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30518940", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 378, "text": "The zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1386, "text": "Further, we also demonstrate that zld is critical for posterior segmentation in the hemipteran Rhodnius prolixus, indicating this function predates the origin of holometabolous insects and was subsequently lost in long-germ insects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "endSection": "abstract" }, { "offsetInBeginSection": 1419, "offsetInEndSection": 1536, "text": "Overall our analysis suggests that GAF, together with Zelda, plays an important role in activating the zygotic genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676122", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 477, "text": " In Drosophila melanogaster, the transcription factor Zelda plays an essential role in widespread activation of the zygotic genome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29261646", "endSection": "abstract" }, { "offsetInBeginSection": 1817, "offsetInEndSection": 1952, "text": "This demonstrates that highly regulated levels of Zelda activity are required for establishing the developmental program during the MZT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29261646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335633", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 659, "text": "Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335633", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 539, "text": "Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 424, "text": "In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 497, "text": "Although the mechanisms driving this genome activation are currently unknown, the transcriptional activator Zelda (ZLD) has been shown to be instrumental in driving this process in Drosophila melanogaster. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25538246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Zelda potentiates morphogen activity by increasing chromatin accessibility.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "endSection": "title" }, { "offsetInBeginSection": 341, "offsetInEndSection": 536, "text": "Zelda (Zld) plays such a role in the Drosophila embryo, where it has been shown to control the action of patterning signals; however, the mechanisms underlying this effect remain largely unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "endSection": "abstract" }, { "offsetInBeginSection": 1595, "offsetInEndSection": 1773, "text": "rthermore, a putative homologue of the Zelda gene has been considered, which in D. melanogaster encodes a DNA-binding factor responsible for the maternal-to-zygotic transition.CO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20102629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "In the endopterygote Drosophila\u00a0melanogaster, Zelda is an activator of the zygotic genome during the maternal-to-zygotic transition (MZT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30993896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The transcription factor Zelda plays a pivotal role in promoting the maternal to zygotic transition during embryogenesis in Drosophila melanogaster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "A conserved maternal-specific repressive domain in Zelda revealed by Cas9-mediated mutagenesis in Drosophila melanogaster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29261646", "endSection": "title" }, { "offsetInBeginSection": 163, "offsetInEndSection": 377, "text": "The zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 385, "text": "zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility. D. mela", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The Drosophila Zelda transcription factor plays an important role in regulating transcription at the embryonic maternal-to-zygotic transition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22537497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "BACKGROUND: The protein Zelda was shown to play a key role in early Drosophila development, binding thousands of promoters and enhancers prior to maternal-to-zygotic transition (MZT), and marking them for transcriptional", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676122", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 755, "text": "A second maternally deposited factor, Zelda (Zld), is uniformly distributed in the embryo and is thought to act as a pioneer factor, increasing enhancer accessibility for transcription factors, such as Dl [3-9].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30982648", "endSection": "abstract" } ] }, { "body": "What does tsDMARD stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32550671", "http://www.ncbi.nlm.nih.gov/pubmed/32896492", "http://www.ncbi.nlm.nih.gov/pubmed/32179964", "http://www.ncbi.nlm.nih.gov/pubmed/31787605", "http://www.ncbi.nlm.nih.gov/pubmed/31426398", "http://www.ncbi.nlm.nih.gov/pubmed/30941350", "http://www.ncbi.nlm.nih.gov/pubmed/30128641", "http://www.ncbi.nlm.nih.gov/pubmed/28831712", "http://www.ncbi.nlm.nih.gov/pubmed/31504972", "http://www.ncbi.nlm.nih.gov/pubmed/31682274", "http://www.ncbi.nlm.nih.gov/pubmed/27118331" ], "ideal_answer": [ "tsDMARDs are targeted synthetic disease-modifying antirheumatic drugs." ], "exact_answer": [ "targeted synthetic disease-modifying antirheumatic drugs" ], "type": "factoid", "id": "602598101cb411341a0000ae", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 319, "text": "Whether this potential risk is specific to abatacept or extends to all biologics and targeted synthetic DMARDs (tsDMARDs) is unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31504972", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 433, "text": "To provide real-world evidence about the reasons why Australian rheumatologists cease biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) when treating patients with rheumatoid arthritis (RA), and to assess (1) the primary failure rate for first-line treatment, and (2) the persistence on second-line treatments in patients who stopped first-line tumor necrosis factor inhibitors (TNFi).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31787605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "The treatment of rheumatoid arthritis (RA) has been transformed with the introduction of biologic disease modifying anti-rheumatic drugs (bDMARD) and more recently, targeted synthetic DMARD (tsDMARD) therapies in the form of janus-kinase inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30941350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Despite recommendations suggesting that biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) should be used in combination with methotrexate in the treatment of rheumatoid arthritis (RA), up to one-third of patients with RA are treated with monotherapy. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30128641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Many biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are currently available as treatment options for rheumatoid arthritis (RA), but a subset of RA patients shows inadequate responses to any of these DMARDs. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32896492", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 350, "text": "A Jak inhibitor tofacitinib, the first drug of targeted synthetic DMARD (tsDMARD), a novel category of DMARD, shows similar efficacy profile, but different safety concerns, compared to bDMARDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27118331", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 279, "text": "Clinical trials of biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have included fatigue as a secondary endpoint.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31682274", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 980, "text": "Furthermore, targeted synthetic DMARDs (tsDMARDs) inhibiting Janus kinase (JAK) and biosimilars also are approved for RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28831712", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 643, "text": "Treatment wise, great progress has been achieved over the last decades with the discovery and introduction in therapeutics of new molecules, such as the biological (b) disease-modifying anti-rheumatic drugs (DMARDs), and the targeted synthetic (ts) DMARDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31426398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "The progress in the understanding of the pathophysiology of rheumatic diseases provided a rational basis for the development of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) which have completely revolutionized the treatment of inflammatory conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32550671", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 379, "text": "These new drugs consist of biologicals (biological disease-modifying antirheumatic drugs, bDMARDs) as well as targeted synthetic DMARDs (tsDMARD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32179964", "endSection": "abstract" } ] }, { "body": "Which conditions are manifested by TRIM8 mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32531461" ], "ideal_answer": [ "TRIM8 mutations are associated with epilepsy, epileptic encephalopathy, developmental delay and intellectual disability.", "Mutations in the TRIM8 gene, which encodes the triggering receptor encoded in myeloid cells 8 (TRIM8) are associated with epilepsy, epileptic encephalopathy, developmental delay and intellectual disability.", "Focal segmental glomerulosclerosis, severe developmental delay, intellectual disability and epilepsy.", "Mutations in TRIM8 gene have been described in patients with severe developmental delay, epileptic encephalopathy, developmental delay and intellectual disability." ], "exact_answer": [ [ "Focal segmental glomerulosclerosis" ], [ "Severe developmental delay" ], [ "Intellectual disability" ], [ "Epilepsy" ] ], "type": "list", "id": "601d6ec61cb411341a000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Focal segmental glomerulosclerosis and mild intellectual disability in a patient with a novel de novo truncating TRIM8 mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32531461", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1434, "text": "Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32531461", "endSection": "abstract" } ] }, { "body": "What is LY-CoV555?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33113295", "http://www.ncbi.nlm.nih.gov/pubmed/33024963", "http://www.ncbi.nlm.nih.gov/pubmed/33215063" ], "ideal_answer": [ "LY-CoV555 is an anti-spike neutralizing antibody targeting the SARS-CoV-2 that has been tested for patients with Covid-19." ], "type": "summary", "id": "601c13b61cb411341a00000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33113295", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33024963", "endSection": "title" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 1646, "text": "As of 8 August 2020, eight antibody candidates targeting the SARS-CoV-2\u00a0S protein have entered clinical studies, including LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33215063", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 672, "text": "METHODS: In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33113295", "endSection": "abstract" }, { "offsetInBeginSection": 1793, "offsetInEndSection": 2016, "text": "CONCLUSIONS: In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33113295", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 299, "text": "Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33024963", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 1007, "text": "One Sentence Summary: LY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33024963", "endSection": "abstract" } ] }, { "body": "List blood marker for Non-Hodgkin lymphoma.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29725472", "http://www.ncbi.nlm.nih.gov/pubmed/29930163", "http://www.ncbi.nlm.nih.gov/pubmed/26656543" ], "ideal_answer": [ "Soluble interleukin-2 receptor-\u03b1, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes.\nGALECTIN-3 AS A PROGNOSTIC BIOMARKER IN PATIENTS WITH NON-HODGKIN LYMPHOMA." ], "exact_answer": [ [ "Soluble interleukin-2 receptor-\u03b1" ], [ "CXC chemokine ligand 13" ], [ "soluble CD30" ], [ "soluble tumor necrosis factor receptor-2" ], [ "B-cell activating factor" ], [ "Galectin-3" ] ], "type": "list", "id": "5e92015b2d3121100d000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "To date, there have been a limited number of useful biomarkers for the screening and monitoring of B-cell non-Hodgkin's lymphoma (B-NHL), which leads to the impetus to discover novel biomarkers for the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29725472", "endSection": "abstract" }, { "offsetInBeginSection": 1493, "offsetInEndSection": 1684, "text": "immune activation precedes non-Hodgkin lymphoma diagnosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29930163", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1109, "text": "Soluble interleukin-2 receptor-\u03b1, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29930163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "GALECTIN-3 AS A PROGNOSTIC BIOMARKER IN PATIENTS WITH NON-HODGKIN LYMPHOMA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26656543", "endSection": "title" } ] }, { "body": "Are bacteria in the genus Clostridium facultative anaerobes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26231446", "http://www.ncbi.nlm.nih.gov/pubmed/25700419", "http://www.ncbi.nlm.nih.gov/pubmed/31076745", "http://www.ncbi.nlm.nih.gov/pubmed/20526574", "http://www.ncbi.nlm.nih.gov/pubmed/31991218", "http://www.ncbi.nlm.nih.gov/pubmed/18430081", "http://www.ncbi.nlm.nih.gov/pubmed/21067677" ], "ideal_answer": [ "Clostridia belong to those bacteria which are considered as obligate anaerobe, e.g. oxygen is harmful or lethal to these bacteria.", "No, bacteria in the genus Clostridium are obligate anaerobes" ], "exact_answer": "no", "type": "yesno", "id": "5e6f774ec6a8763d23000009", "snippets": [ { "offsetInBeginSection": 50, "offsetInEndSection": 92, "text": "strict anaerobe Clostridium acetobutylicum", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18430081", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Clostridia belong to those bacteria which are considered as obligate anaerobe, e.g. oxygen is harmful or lethal to these bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18430081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "We report here the closed genome of Clostridium pasteurianum ATCC 6013, a saccharolytic, nitrogen-fixing, and spore-forming Gram-positive obligate anaerobe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25700419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Clostridium pasteurianum BB, a saccharolytic and spore-forming obligate anaerobe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21067677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Clostridium difficile is a spore-forming obligate anaerobe that is a leading cause of healthcare-associated infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26231446", "endSection": "abstract" }, { "offsetInBeginSection": 537, "offsetInEndSection": 682, "text": "However, the discovery of antimicrobials has been biased towards aerobes and facultative anaerobes, and strict anaerobes such as Clostridium spp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31991218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Clostridium is a large genus of obligate anaerobes belonging to the Firmicutes phylum of bacteria, most of which have a Gram-positive cell wall structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31076745", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 665, "text": "Such bacteria are either obligate anaerobic bacteria like Clostridium or Bifidobacterium or facultative anaerobic like Escherichia coli or Salmonella.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20526574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Antimicrobial production by strictly anaerobic Clostridium spp.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31991218", "endSection": "title" } ] }, { "body": "Do nematodes contain architectural proteins like CTCF?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "http://www.ncbi.nlm.nih.gov/pubmed/17442748", "http://www.ncbi.nlm.nih.gov/pubmed/29385718" ], "ideal_answer": [ "insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode.", "the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans.", "No, nematodes do not contain architectural proteins such as CTCF.", "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans.", "No. Most nematodes do not contain architectural proteins like CTCF.", "No, nematodes do not contain architectural proteins like CTCF.", "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. \u03a4he insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans.", "No, nematodes contain architectural proteins such as CTCF." ], "exact_answer": "no", "type": "yesno", "id": "5fdb4253a43ad31278000022", "snippets": [ { "offsetInBeginSection": 198, "offsetInEndSection": 400, "text": "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 1267, "offsetInEndSection": 1357, "text": "the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 981, "text": "he most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17442748", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1361, "text": "uggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 989, "text": "of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier st", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385718", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 659, "text": "SULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Loss of the insulator protein CTCF during nematode evolution", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "title" }, { "offsetInBeginSection": 766, "offsetInEndSection": 970, "text": "que secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In con", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385718", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 391, "text": "level. A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1359, "text": " suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Loss of the insulator protein CTCF during nematode evolution.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "title" } ] }, { "body": "What is the primary indication of tocilizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31859424" ], "ideal_answer": [ "Tocilizumab is considered first-line treatment for rheumatoid arthritis." ], "exact_answer": [ "Rheumatoid arthritis" ], "type": "factoid", "id": "60258edd1cb411341a0000a9", "snippets": [ { "offsetInBeginSection": 1179, "offsetInEndSection": 1339, "text": "For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31859424", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 173, "text": "Approximately 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARDs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31859424", "endSection": "abstract" } ] }, { "body": "Describe efforts on Sarcoma from the 100,000 Genomes Project", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32573957" ], "ideal_answer": [ "The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5\u2009years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. A specialist sarcoma centre recruited close to 1000 patients to the project. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant-calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design.", "The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5\u2009years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. The number of informative genomes produced was reduced further by a PCR amplification step." ], "type": "summary", "id": "601d72a31cb411341a000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1956, "text": "The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5\u2009years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. Herein, we recount the lessons learned by a specialist sarcoma centre that recruited close to 1000 patients to the project, so that we and others may learn from our experience. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. We showed that this loss of genomic data could be mitigated by sequencing whole genomes from needle core biopsies. Storage of resection specimens at 4\u2009\u00b0C for up to 96\u2009h overcame the challenge of freezing tissue out of hours including weekends. Removing access to formalin increased compliance to these storage arrangements. With over 70 different sarcoma subtypes described, WGS was a useful tool for refining diagnoses and identifying novel alterations. Genomes from 350 of the cohort of 597 patients were analysed in this study. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant-calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32573957", "endSection": "abstract" } ] }, { "body": "What is the goal of the RadRAT calculator?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30514249", "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "http://www.ncbi.nlm.nih.gov/pubmed/27824812" ], "ideal_answer": [ "Radiation risk assessment tool (RadRAT) can be used to estimate the lifetime risk of radiation-related cancer with uncertainty intervals following a user-specified exposure history. The calculator can be used to estimate lifetime cancer risk from both uniform and non-uniform doses that are acute or chronic. It is most appropriate for low-LET radiation doses < 1 Gy, and for individuals with life-expectancy and cancer rates similar to the general population in the US." ], "type": "summary", "id": "5e3393e1fbd6abf43b000063", "snippets": [ { "offsetInBeginSection": 363, "offsetInEndSection": 582, "text": "METHODS: Using estimated organ doses and the RadRAT risk assessment tool, the lifetime cancer risk was estimated among medical radiation workers who were enrolled in the Korean National Dose Registry from 1996 to 2011. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30514249", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 597, "text": "Excess lifetime risks (ELRs) of radiation-related cancer were calculated as cumulative lifetime risks, accounting for survival probabilities, using the RadRAT risk assessment tool.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27824812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "RadRAT: a radiation risk assessment tool for lifetime cancer risk projection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "endSection": "title" }, { "offsetInBeginSection": 335, "offsetInEndSection": 580, "text": "We developed an online radiation risk assessment tool (RadRAT) which can be used to estimate the lifetime risk of radiation-related cancer with uncertainty intervals following a user-specified exposure history (https://irep.nci.nih.gov/radrat). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "endSection": "abstract" }, { "offsetInBeginSection": 1409, "offsetInEndSection": 1698, "text": " The calculator can be used to estimate lifetime cancer risk from both uniform and non-uniform doses that are acute or chronic. It is most appropriate for low-LET radiation doses < 1 Gy, and for individuals with life-expectancy and cancer rates similar to the general population in the US.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 938, "text": "The risk models used in RadRAT are broadly based on those developed by the BEIR VII committee for estimating lifetime risk following low-dose radiation exposure of the US population for eleven site-specific cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 582, "text": " developed an online radiation risk assessment tool (RadRAT) which can be used to estimate the lifetime risk of radiation-related cancer with uncertainty intervals following a user-specified exposure history (https://irep.nci.nih.gov/radrat). Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "RadRAT: a radiation risk assessment tool for lifetime cancer risk projection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "endSection": "title" }, { "offsetInBeginSection": 335, "offsetInEndSection": 579, "text": "We developed an online radiation risk assessment tool (RadRAT) which can be used to estimate the lifetime risk of radiation-related cancer with uncertainty intervals following a user-specified exposure history (https://irep.nci.nih.gov/radrat).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22810503", "endSection": "abstract" } ] }, { "body": "List the deadliest viruses in the world.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20049699", "http://www.ncbi.nlm.nih.gov/pubmed/30252528", "http://www.ncbi.nlm.nih.gov/pubmed/27622648", "http://www.ncbi.nlm.nih.gov/pubmed/29425816", "http://www.ncbi.nlm.nih.gov/pubmed/27979676" ], "ideal_answer": [ "The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), are among the deadliest viruses that cause disease in humans, with reported case fatality rates of up to 90% in some outbreaks.\r\nWHO ranks HIV as one of the deadliest diseases.\r\nInfluenza virus" ], "exact_answer": [ [ "Ebola virus" ], [ "Marburg virus" ], [ "Influenza virus" ], [ "HIV" ] ], "type": "list", "id": "5e92005c2d3121100d000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The Ebola and Marburg viruses are some of the deadliest viruses in the world. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27979676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), are among the deadliest viruses that cause disease in humans, with reported case fatality rates of up to 90% in some outbreaks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27622648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Filoviruses are zoonotic and among the deadliest viruses known to mankind, with mortality rates in outbreaks reaching up to 90%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20049699", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 374, "text": "influenza viruses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30252528", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 322, "text": "WHO ranks HIV as one of the deadliest diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29425816", "endSection": "abstract" } ] }, { "body": "What monoclonal antibody drugs are used to treat late stage melanoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29157311", "http://www.ncbi.nlm.nih.gov/pubmed/28118986", "http://www.ncbi.nlm.nih.gov/pubmed/24477411", "http://www.ncbi.nlm.nih.gov/pubmed/21957431", "http://www.ncbi.nlm.nih.gov/pubmed/23294221", "http://www.ncbi.nlm.nih.gov/pubmed/19018089", "http://www.ncbi.nlm.nih.gov/pubmed/18537753", "http://www.ncbi.nlm.nih.gov/pubmed/23262440", "http://www.ncbi.nlm.nih.gov/pubmed/30539467", "http://www.ncbi.nlm.nih.gov/pubmed/25125216", "http://www.ncbi.nlm.nih.gov/pubmed/25588084", "http://www.ncbi.nlm.nih.gov/pubmed/26105702", "http://www.ncbi.nlm.nih.gov/pubmed/17473208", "http://www.ncbi.nlm.nih.gov/pubmed/26313415", "http://www.ncbi.nlm.nih.gov/pubmed/24770508" ], "ideal_answer": [ "Nivolumab, ipilimumab, vemurafenib, and dabrafenib are used to treat late stage melanoma", "Dabrafenib, ipilimumab and vemurafenib are monoclonal antibodies that are used to treat late stage melanoma.", "Dabrafenib, ipilimumab and vemurafenib are monoclonal antibodies used to treat late-stage melanoma.", "Dabrafenib, ipilimumab and vemurafenib are monoclonal antibodies that are used to treat late-stage melanoma." ], "exact_answer": [ [ "ipilimumab" ], [ "Nivolumab" ], [ "vemurafenib" ], [ "dabrafenib" ] ], "type": "list", "id": "5e639d081af46fc130000014", "snippets": [ { "offsetInBeginSection": 1618, "offsetInEndSection": 2045, "text": " Nivolumab, a fully human monoclonal antibody against programmed cell death protein 1 (PD-1), has shown a survival benefit in an open-label phase II trial, and was the first PD-1 inhibitor to be approved worldwide. With a favorable side effect profile and ongoing trials in combination with extant therapies, nivolumab shows substantial potential to further augment the options for an effective treatment in malignant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25588084", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 140, "text": " Checkpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157311", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 170, "text": "ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157311", "endSection": "title" }, { "offsetInBeginSection": 26, "offsetInEndSection": 80, "text": "ate-stage cutaneous melanoma treated with vemurafenib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25125216", "endSection": "title" }, { "offsetInBeginSection": 213, "offsetInEndSection": 319, "text": "ome of the drugs thus developed, such as vemurafenib and dabrafenib, show impressive responses in melanoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23294221", "endSection": "abstract" }, { "offsetInBeginSection": 39, "offsetInEndSection": 82, "text": "ipilimumab therapy for metastatic melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262440", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Melanoma is the deadliest form of skin cancer. Ipilimumab, a novel immunotherapy, is the first treatment shown to improve survival in patients with metastatic melanoma in large randomized controlled studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23262440", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 652, "text": "In 2011, new drugs were approved by the U.S. Food and Drug Administration, including peginterferon alfa-2b for patients with stage III disease, vemurafenib for patients with metastatic melanoma with the BRAF V600E mutation, and ipilimumab, a monoclonal antibody directed to the CTLA-4 T lymphocyte receptor, to combat metastatic melanoma in patients who do not have the BRAF V600E mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24770508", "endSection": "abstract" }, { "offsetInBeginSection": 1251, "offsetInEndSection": 1500, "text": "Foremost among these was ipilimumab, a monoclonal antibody against the negative regulatory checkpoint molecule cytotoxic T-lymphocyte protein 4 (CTLA-4), which was the first drug in the management of metastatic melanoma to confer a survival benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25588084", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1523, "text": "was ipilimumab, a monoclonal antibody against the negative regulatory checkpoint molecule cytotoxic T-lymphocyte protein 4 (CTLA-4), which was the first drug in the management of metastatic melanoma to confer a survival benefit. However, treatment is ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25588084", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 887, "text": "TLA-4 monoclonal antibody ipilimumab has already been approved in advanced melanoma and two phase III trials evaluating ipilimumab in men with metastatic castrate-resistant prostate cancer are underway. A phase ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24477411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Nivolumab and pembrolizumab as immune-modulating monoclonal antibodies targeting the PD-1 receptor to treat melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313415", "endSection": "title" }, { "offsetInBeginSection": 541, "offsetInEndSection": 768, "text": "Ipilimumab, the first monoclonal antibody to be approved for the treatment of metastatic melanoma, showed significant improvements in durable response rates in patients and paved the way for next class of monoclonal antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30539467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Anti-CTLA4 monoclonal antibody Ipilimumab in the treatment of metastatic melanoma: recent findings.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18537753", "endSection": "title" }, { "offsetInBeginSection": 598, "offsetInEndSection": 895, "text": "Nivolumab and pembrolizumab (formerly lambrolizumab), the two FDA-approved anti-programmed death-1 monoclonal antibodies, show highly durable response rates and long-term safety, validating the importance of the programmed cell death protein 1 pathway blockade for treatment of malignant melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "The anti-programmed cell death-1 (PD-1) monoclonal antibodies pembrolizumab and nivolumab have been contingently approved for the treatment of patients with advanced melanoma based on their durable response, high response rate, and favorable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26105702", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 592, "text": "Enhancement of the immune system by blockade of the cytotoxic T-lymphocyte associated antigen-4 by the monoclonal antibody ipilimumab is now approved by the United States Food and Drug Administration (FDA) for use in patients with unresectable melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21957431", "endSection": "abstract" } ] }, { "body": "Which transcription factor controls Drosophila's Hes genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28144959", "http://www.ncbi.nlm.nih.gov/pubmed/9152013", "http://www.ncbi.nlm.nih.gov/pubmed/17028039", "http://www.ncbi.nlm.nih.gov/pubmed/17586813", "http://www.ncbi.nlm.nih.gov/pubmed/19050759", "http://www.ncbi.nlm.nih.gov/pubmed/25248479", "http://www.ncbi.nlm.nih.gov/pubmed/9570950", "http://www.ncbi.nlm.nih.gov/pubmed/23300480", "http://www.ncbi.nlm.nih.gov/pubmed/9291577", "http://www.ncbi.nlm.nih.gov/pubmed/15893982", "http://www.ncbi.nlm.nih.gov/pubmed/23274689", "http://www.ncbi.nlm.nih.gov/pubmed/33229432", "http://www.ncbi.nlm.nih.gov/pubmed/14648848", "http://www.ncbi.nlm.nih.gov/pubmed/9819428" ], "ideal_answer": [ "The Notch/Hes axis represses a cohort of transcription factor genes . In Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES) genes, which shut off achaete-scute transcription . The molecular details of how Hes and Hey proteins control transcription are still poorly understood .", "Hes genes encode factors that mediate many of the activities of the Notch pathway. Hes genes are functionally classified into two groups: those that are regulated by Notch and those that are not.", "Mammalian Hes genes encode transcriptional factors that mediate many of the activities of the Notch pathway. HES transcriptional repressors are important components of the Notch pathway that regulates neurogenesis from Drosophila to vertebrates.", "In Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES) genes, which interact with the Groucho protein to shut off achaete-scute transcription.", "Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. Mammalian Hes genes encode transcriptional factors that mediate many of the activities of the Notch pathway.", "HES transcriptional repressors are important components of the Notch pathway that regulates neurogenesis from Drosophila to vertebrates. Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts. Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction", "The Notch/Hes axis represses a cohort of transcription factor genes . The molecular details of how Hes and Hey proteins control transcription are still poorly understood . In Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES) genes, which act as negative regulators in this process .", "Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction", "Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. Based on these data, we propose a model in which Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts.", "Mammalian Hes genes encode transcriptional factors that mediate many of the activities of the Notch pathway . Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling . The Notch-Hes1 pathway regulates ovarian somatic cell development, which is necessary for oocyte survival and maturation ." ], "exact_answer": [ "Notch" ], "type": "factoid", "id": "5e4bf9436d0a27794100002d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300480", "endSection": "title" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1584, "text": "Based on these data, we propose a model in which Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300480", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 258, "text": "Mammalian Hes genes encode transcriptional factors that mediate many of the activities of the Notch pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23274689", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1336, "text": "In conclusion, our data suggest that the Notch-Hes1 pathway regulates ovarian somatic cell development, which is necessary for oocyte survival and maturation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23274689", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 854, "text": "Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25248479", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 555, "text": "In this study, we identified the Atrophin family protein RERE (also called Atro2) as a positive regulator of Notch target Hes genes in the developing vertebrate spinal cord", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28144959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "HES transcriptional repressors are important components of the Notch pathway that regulates neurogenesis from Drosophila to vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15893982", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 913, "text": "Notch signaling produces an initial burst of hes5 activity, which represses hes6-2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15893982", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 1030, "text": " Transient transfection analyses demonstrated that, while Hes1 and Hes5 promoter activities are significantly upregulated by the active form of Notch, a key regulator of cellular differentiation, Hes2 and Hes3 promoter activities are not. These results suggest that Hes genes are functionally classified into two groups: those that are regulated by Notch and those that are not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9570950", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 365, "text": "hairy and Enhancer of split function in both segmentation and in the Notch neurogenic pathway during Drosophila embryo development. Previous expression data suggested a conserved role for the Hes genes in the Notch signalling pathway, but not in segmentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9152013", "endSection": "abstract" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1617, "text": "These data suggest that Notch signaling through activation of HES transcriptional repressors may play a role in murine placental development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9291577", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 929, "text": "In Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES) genes, which interact with the Groucho protein to shut off achaete-scute transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9291577", "endSection": "abstract" }, { "offsetInBeginSection": 697, "offsetInEndSection": 879, "text": " data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/He", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33229432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19050759", "endSection": "title" }, { "offsetInBeginSection": 543, "offsetInEndSection": 666, "text": "In Drosophila we recently characterized Hamlet, a transcription factor that mediates Notch signalling and neural cell fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19050759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "HESR1 is a basic helix-loop-helix transcription factors regulated by the Notch signaling pathway in vertebrate and Drosophila embryos, and is related to the HES/Hairy/E (sp1) family. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17028039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Hairy-related transcription factor (HRT/Hey) genes encode a novel subfamily of basic helix-loop-helix (bHLH) transcription factors related to the Drosophila hairy and Enhancer-of-split (E(spl)) and the mammalian HES proteins that function as downstream mediators of Notch signaling. Usin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14648848", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 312, "text": "t has been shown in Drosophila melanogaster that Delta-dependent Notch signaling activates the transcription factor Suppressor of Hairless, leading to an increased expression of the Enhancer of Split genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9819428", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 487, "text": "Here we analyze genome-wide changes in transcript levels, binding of the Notch pathway transcription factor, CSL [Suppressor of Hairless, Su(H), in Drosophila], and RNA Polymerase II (Pol II) immediately following a short pulse of Notch stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300480", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 920, "text": "Other genes had a more delayed response, the timing of which was largely unaffected by more prolonged Notch activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Hes and Hey genes are the mammalian counterparts of the Hairy and Enhancer-of-split type of genes in Drosophila and they represent the primary targets of the Delta-Notch signaling pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17586813", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 935, "text": "We show that the Notch/Hes axis represses a cohort of transcription factor genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33229432", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1176, "text": "Furthermore, we observed that Dl-1-induced HES-1 transactivation was dependent both on Kuzbanian and RBP-J activities, consistent with the involvement of these two proteins in Notch signaling in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9819428", "endSection": "abstract" } ] }, { "body": "Is tocilizumab a tumor necrosis factor inhibitor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31859424" ], "ideal_answer": [ "No, tocilizumab, is a non-TNFi DMARD." ], "exact_answer": "no", "type": "yesno", "id": "6025912a1cb411341a0000aa", "snippets": [ { "offsetInBeginSection": 1179, "offsetInEndSection": 1339, "text": "For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31859424", "endSection": "abstract" } ] }, { "body": "Describe manifestations of KIF1A-related disorders in children", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32096284" ], "ideal_answer": [ "KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. A study identified twelve individuals from 10 families. Eight different mutations were present, including four novel mutations. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress. The remaining 10 patients represented a spectrum of severity with common features including a movement disorder with spasticity and/or dystonia, subtle features of dysautonomia, sensory axonal neuropathy, varying degrees of optic atrophy and of learning and/or behavioural difficulties, and subtle or absent-but sometimes progressive-changes in white matter on MRI. Epilepsy was common among the more severely affected children.", "KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress." ], "type": "summary", "id": "601d35111cb411341a00002f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1563, "text": "KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Here we present a case series demonstrating the range of clinical, neurophysiological, and radiological features which may occur in childhood-onset KRD. We report on all the children and young people seen at a single large tertiary centre. Data were collected through a retrospective case-notes review. Twelve individuals from 10 families were identified. Eight different mutations were present, including four novel mutations. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress. The remaining 10 patients represented a spectrum of severity with common features including a movement disorder with spasticity and/or dystonia, subtle features of dysautonomia, sensory axonal neuropathy, varying degrees of optic atrophy and of learning and/or behavioural difficulties, and subtle or absent-but sometimes progressive-changes in white matter on MRI. Epilepsy was common among the more severely affected children. This case series demonstrates that KRD comprise a range of neurological disorders, with both the milder and the more severe forms combining central and peripheral (including autonomic) nervous system deficits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32096284", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of pitolisant.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27902931", "http://www.ncbi.nlm.nih.gov/pubmed/27568835", "http://www.ncbi.nlm.nih.gov/pubmed/27438291", "http://www.ncbi.nlm.nih.gov/pubmed/22356925", "http://www.ncbi.nlm.nih.gov/pubmed/29802412", "http://www.ncbi.nlm.nih.gov/pubmed/32565240", "http://www.ncbi.nlm.nih.gov/pubmed/27787717", "http://www.ncbi.nlm.nih.gov/pubmed/28129985", "http://www.ncbi.nlm.nih.gov/pubmed/22820944", "http://www.ncbi.nlm.nih.gov/pubmed/30359639", "http://www.ncbi.nlm.nih.gov/pubmed/28490912", "http://www.ncbi.nlm.nih.gov/pubmed/31997137", "http://www.ncbi.nlm.nih.gov/pubmed/28777172", "http://www.ncbi.nlm.nih.gov/pubmed/32782417", "http://www.ncbi.nlm.nih.gov/pubmed/32032921", "http://www.ncbi.nlm.nih.gov/pubmed/31937172", "http://www.ncbi.nlm.nih.gov/pubmed/33117007", "http://www.ncbi.nlm.nih.gov/pubmed/31917607", "http://www.ncbi.nlm.nih.gov/pubmed/24107292", "http://www.ncbi.nlm.nih.gov/pubmed/28449891", "http://www.ncbi.nlm.nih.gov/pubmed/30503715" ], "ideal_answer": [ "Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. It is used for treatment of narcolepsy." ], "type": "summary", "id": "5e48bb12d14c9f295d000016", "snippets": [ { "offsetInBeginSection": 527, "offsetInEndSection": 1291, "text": "Given the breadth of compounds developed and potential therapeutic indications, we assessed the comparative pharmacology of six investigational histamine H3 agents, including pitolisant, using native tissue and recombinant cells. Whilst all of the compounds tested displayed robust histamine H3 receptor inverse agonism and did not differentiate between the main H3 receptor splice variants, they displayed a wide range of affinities and kinetic properties, and included rapidly dissociating (pitolisant, S 38093-2, ABT-239) and slowly dissociating (GSK189254, JNJ-5207852, PF-3654746) agents. S 38093-2 had the lowest histamine H3 receptor affinity (pKB values 5.7-6.2), seemingly at odds with previously reported, potent in vivo activity in models of cognition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359639", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The pharmacological profile of pitolisant, a histamine H3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29802412", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 759, "text": "Clinical trials have demonstrated efficacy for the following classes of drugs as narcolepsy treatments: alerting medications (amphetamine, methylphenidate, modafinil/armodafinil, solriamfetol [JZP-110]), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), sodium oxybate, and the H3-receptor inverse agonist/antagonist pitolisant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30503715", "endSection": "abstract" }, { "offsetInBeginSection": 1540, "offsetInEndSection": 1726, "text": "In March 2016, the European Commission granted a marketing authorisation for pitolisant (WakixR) (as the first representative of the H3 inverse agonists) for the treatment of narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27787717", "endSection": "abstract" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1195, "text": "They can be used for therapeutic purposes; e.g., the \u03b12-adrenoceptor antagonist mirtazapine is used as an antidepressant and the inverse histamine H3 receptor agonist pitolisant has been marketed as a new drug for the treatment of narcolepsy in 2016. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27902931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "BACKGROUND: Histaminergic neurons are crucial to maintain wakefulness, but their role in cataplexy is unknown. We assessed the safety and efficacy of pitolisant, a histamine H3 receptor inverse agonist, for treatment of cataplexy in patients with narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28129985", "endSection": "abstract" }, { "offsetInBeginSection": 1475, "offsetInEndSection": 1783, "text": "Several newer wake-promoting agents and psychostimulants have also been developed, including sodium oxybate, which has a role in the treatment of cataplexy and as an adjunctive wake-promoting agent, and pitolisant, a selective histamine H3 receptor inverse agonist that is currently only available in Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28777172", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 862, "text": "The small molecule drug, pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus increasing histaminergic tone in the wake promoting system of the brain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28490912", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 303, "text": "Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28449891", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 881, "text": "rug, pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus increasing histaminergic tone in the wake promoting system of the brain. Pitolisant has been", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28490912", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 354, "text": "e tone). Drugs such as pitolisant, which block histamine H3 autoreceptors, constitute a newly identified class of stimulants because they increase brain histamine and enhance wakefulness in animal and human adult nar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22356925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The pharmacological profile of pitolisant, a histamine H3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29802412", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1196, "text": "can be used for therapeutic purposes; e.g., the \u03b12-adrenoceptor antagonist mirtazapine is used as an antidepressant and the inverse histamine H3 receptor agonist pitolisant has been marketed as a new drug for the treatment of narcolepsy in 2016. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27902931", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 553, "text": "ition to this epigenetic approach, pitolisant as G-protein coupled histamine H3 receptor (H3R) antagonist has demonstrated promising therapeutic effects for Prader-Willi syndrome. To c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32782417", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 438, "text": "levels. In previous studies, we have shown that pitolisant, a histamine H3 receptor antagonist/inverse agonist and \u03c31 receptor agonist, prevented the development of certain metabolic and depressive-like disorders in mice that have been treated chronically with ola", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32565240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome.Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airw", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31917607", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 297, "text": "Pitolisant is a first-in-class drug acting on histamine 3 receptors and indicated for the treatment of narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31937172", "endSection": "abstract" }, { "offsetInBeginSection": 783, "offsetInEndSection": 863, "text": "Expert opinion: Pitolisant is a histamine 3 receptor antagonist/inverse agonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31937172", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 451, "text": "Pitolisant is a first-in-class agent utilizing histamine to improve wakefulness by acting as an antagonist/inverse agonist of the presynaptic histamine 3 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33117007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Pitolisant (Wakix\u2122) is an inverse agonist of the histamine H3 receptor that is being developed by Bioproject.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27438291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "OBJECTIVE AND DESIGN: Pitolisant (BF2.649) is a selective inverse agonist for the histamine H(3) receptor and was developed for the treatment of excessive daytime sleepiness in Parkinson disease, narcolep", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22820944", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "Pitolisant (Wakix\u00ae), an orally available, first-in-class antagonist/inverse agonist of the histamine 3 receptor, is approved in the EU (as of March 2016) for the treatment of narcolepsy with or without cataplexy in adults and in the USA (as of August 2019) for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31997137", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1246, "text": "Pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, is approved by the European Medicines Agency (EMA) for the treatment of narcolepsy with or without cataplexy in adults and by the FDA for the treatment of EDS in adults with narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32032921", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 622, "text": "In contrast, Pitolisant is a non-imidazole H3 receptor inverse agonist that has already been tested in clinical trials but it remains to be determined whether this compound also potentiates the behavioral effects of cocaine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568835", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 323, "text": "akefulness. We assessed the safety and efficacy of pitolisant (previously called BF2.649), a selective histamine H3 receptor inverse agonist that activates these neurons, in patients with", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107292", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 548, "text": "In addition to this epigenetic approach, pitolisant as G-protein coupled histamine H3 receptor (H3R) antagonist has demonstrated promising therapeutic effects for Prader-Willi syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32782417", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 863, "text": "We performed a systematic review of the literature using PubMed and the following keywords were used: 'pitolisant' and 'narcolepsy', 'cataplexy' and 'excessive daytime sleepiness' and 'histamine 3 receptor'.Expert opinion: Pitolisant is a histamine 3 receptor antagonist/inverse agonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31937172", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 437, "text": " levels. In previous studies, we have shown that pitolisant, a histamine H3 receptor antagonist/inverse agonist and \u03c31 receptor agonist, prevented the development of certain metabolic and depressive-like disorders in mice that have been treated chronically with ol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32565240", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 861, "text": "The small molecule drug, pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus increasing histaminergic tone in the wake promoting system of the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28490912", "endSection": "abstract" } ] }, { "body": "What is endoplasmic reticulum stress?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28833755", "http://www.ncbi.nlm.nih.gov/pubmed/26842780", "http://www.ncbi.nlm.nih.gov/pubmed/28295916" ], "ideal_answer": [ "Endoplasmic reticulum stress,\" an imbalance between protein folding load and capacity leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen, has been implicated in rheumatoid arthritis and other inflammatory and metabolic diseases.\nEndoplasmic reticulum stress is associated with the pathophysiology of various liver diseases. Endoplasmic reticulum stress mediates the accumulation of abnormal proteins and leads to oxidative stress, cytoplasmic inclusion body formation, and apoptosis in hepatocytes.\nThe endoplasmic reticulum stress response (ERSR) is activated in a variety of neurodegenerative diseases and/or traumatic injuries. Subsequent restoration of ER homeostasis may contribute to improvement in the functional outcome of these diseases.", "Endoplasmic reticulum stress is an imbalance between protein folding load and capacity leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen." ], "type": "summary", "id": "5e920ddf2d3121100d00000d", "snippets": [ { "offsetInBeginSection": 169, "offsetInEndSection": 431, "text": "Endoplasmic reticulum stress,\" an imbalance between protein folding load and capacity leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen, has been implicated in rheumatoid arthritis and other inflammatory and metabolic diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28833755", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 273, "text": "Endoplasmic reticulum stress is associated with the pathophysiology of various liver diseases. Endoplasmic reticulum stress mediates the accumulation of abnormal proteins and leads to oxidative stress, cytoplasmic inclusion body formation, and apoptosis in hepatocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28295916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The endoplasmic reticulum stress response (ERSR) is activated in a variety of neurodegenerative diseases and/or traumatic injuries. Subsequent restoration of ER homeostasis may contribute to improvement in the functional outcome of these diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26842780", "endSection": "abstract" } ] }, { "body": "What is an operon?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21558189", "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "http://www.ncbi.nlm.nih.gov/pubmed/17169972", "http://www.ncbi.nlm.nih.gov/pubmed/26081635", "http://www.ncbi.nlm.nih.gov/pubmed/7003354", "http://www.ncbi.nlm.nih.gov/pubmed/16716751", "http://www.ncbi.nlm.nih.gov/pubmed/30953757", "http://www.ncbi.nlm.nih.gov/pubmed/25936768", "http://www.ncbi.nlm.nih.gov/pubmed/18356490", "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "http://www.ncbi.nlm.nih.gov/pubmed/16755590", "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "http://www.ncbi.nlm.nih.gov/pubmed/3300731", "http://www.ncbi.nlm.nih.gov/pubmed/21125494" ], "ideal_answer": [ "An operon is a group of genes linked together in a linear fashion and producing polycistronic mRNA.", "genes are contained in operons, multigene clusters controlled by a single promoter. s. An operon is a group of genes linked together in a linear fashion and producing a polycistronic mRNA.", "An operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter." ], "type": "summary", "id": "5e6e751351b80c9423000005", "snippets": [ { "offsetInBeginSection": 37, "offsetInEndSection": 120, "text": "genes are contained in operons, multigene clusters controlled by a single promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25936768", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 721, "text": "s. An operon is a group of genes linked together in a linear fashion and producing a polycistronic mRNA. Trans-acting factors regulate the transcription of these genes by interacting with promoter/regulatory sequences in the 5'-flanking region of the most 5'-ward of the genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3300731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The regulation of gene expression was studied, for the Escherichia coli rpoBC operon, which includes the genes, rpoB and rpoC, for the beta and beta subunits of RNA polymerase, and rplJ and rplL,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7003354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "The lux operon is an uncommon gene cluster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17169972", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1691, "text": "An analysis of operon gene expression from nine different EST libraries indicated that for 587 operons, all of the genes that comprise an individual operon were expressed together in at least one EST library, suggesting that these genes may be co-regulated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21558189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "A post-transcriptional operon is a set of monocistronic mRNAs encoding functionally related proteins that are co-regulated by a group of RNA-binding proteins and/or small non-coding RNAs so that protein expression is coordinated at the post-transcriptional level. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21125494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "An operon is a set of neighboring genes in a genome that is transcribed as a single polycistronic message.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30953757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "The operon is a specific functional organization of genes found in bacterial genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16716751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "UNLABELLED: Operons are multigene transcriptional units which occur mostly in prokaryotes but rarely in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26081635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Operons are clusters of genes that are transcribed as a single message, and regulated by the same gene expression machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16755590", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 273, "text": "Operons are regulated multigene transcription units, in which polycistronic pre-messenger RNA (pre-mRNA coding for multiple peptides) is processed to monocistronic mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Operons are clusters of genes that are co-regulated from a common promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21558189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Genes in nematode and ascidian genomes frequently occur in operons--multiple genes sharing a common promoter to generate a polycistronic primary transcript--and such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The organization of genes into operons, clusters of genes that are co-transcribed to produce polycistronic pre-mRNAs, is a trait found in a wide range of eukaryotic groups, including multiple animal phyla.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Operons are clusters of unrelated genes with related functions that are a feature of prokaryotic genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18356490", "endSection": "abstract" } ] }, { "body": "Do circular exons increase gene expression?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25253891", "http://www.ncbi.nlm.nih.gov/pubmed/28634583", "http://www.ncbi.nlm.nih.gov/pubmed/21151960", "http://www.ncbi.nlm.nih.gov/pubmed/30136305", "http://www.ncbi.nlm.nih.gov/pubmed/28184940", "http://www.ncbi.nlm.nih.gov/pubmed/8652136" ], "ideal_answer": [ "circRNAs might adsorb specific miRNAs to regulate the expression of their target gene mRNAs. They can thus lead to both over- and under-expression of mRNAs." ], "exact_answer": "no", "type": "yesno", "id": "5e43ee1f48dab47f26000012", "snippets": [ { "offsetInBeginSection": 873, "offsetInEndSection": 1096, "text": "Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151960", "endSection": "abstract" }, { "offsetInBeginSection": 1672, "offsetInEndSection": 1883, "text": "These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21151960", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 833, "text": "To explore the potential for using this methodology to express circular RNA in vivo, circular forms of the HDV ribozyme and RNaseP RNA were produced in E. coli. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8652136", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1079, "text": "The activity of in vivo expressed circular ribozymes could be demonstrated indicating that they fold into active conformation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8652136", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 865, "text": "We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28184940", "endSection": "abstract" }, { "offsetInBeginSection": 1861, "offsetInEndSection": 2012, "text": "These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC in the future", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28184940", "endSection": "abstract" }, { "offsetInBeginSection": 1627, "offsetInEndSection": 1763, "text": "69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28184940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25253891", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "The highly structured (64% GC) covalently closed circular (CCC) RNA (220 nt) of the virusoid associated with rice yellow mottle virus codes for a 16-kDa highly basic protein using novel modalities for coding, translation, and gene expression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25253891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30136305", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1161, "text": "It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634583", "endSection": "abstract" } ] }, { "body": "What does CMB305 contain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29280411" ], "ideal_answer": [ "CMB305 includes a boost from a NY-ESO-1 protein vaccine given along with a potent toll-like-4 receptor agonist, glycopyranosyl lipid A." ], "exact_answer": [ [ "NY-ESO-1 protein vaccine" ], [ "glycopyranosyl lipid A" ] ], "type": "list", "id": "5e7f63f5835f4e477700001d", "snippets": [ { "offsetInBeginSection": 310, "offsetInEndSection": 390, "text": "In this review, we discuss the novel NY-ESO-1 targeted vaccine regimen, CMB305. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29280411", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 814, "text": "CMB305 also includes a boost from a NY-ESO-1 protein vaccine given along with a potent toll-like-4 receptor agonist, glycopyranosyl lipid A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29280411", "endSection": "abstract" } ] }, { "body": "What kind of mutations cause GRK1 associated Oguchi disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33252155" ], "ideal_answer": [ "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Hutchinson-Gilford disease as well as congenital stationary night blindness in around 90% of patients.", "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB).", "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare autosomal recessive disorder characterized by congenital stationary night blindness (CSNB).", "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB)", "Biallelic mutations in G-Protein coupled receptor kinase 1 cause Oguchi disease. Oguchi disease is a rare subtype of congenital stationary night blindness." ], "exact_answer": [ "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1)" ], "type": "factoid", "id": "601bcb5d1cb411341a000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33252155", "endSection": "abstract" } ] }, { "body": "Is MAGE-A3 immunotherapeutic effective for non-small-cell lung cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27132212" ], "ideal_answer": [ "No. In a randomized, double-blind, placebo-controlled, phase 3 trial (MAGE-A3-positive non-small-cell lung cancer; MAGRIT), adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected non-small-cell lung cancer. Based on these results, further development of the MAGE-A3 immunotherapeutic for use in non-small-cell lung cancer has been stopped." ], "exact_answer": "no", "type": "yesno", "id": "5e4d6e446d0a27794100002f", "snippets": [ { "offsetInBeginSection": 3329, "offsetInEndSection": 3630, "text": "INTERPRETATION: Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27132212", "endSection": "abstract" }, { "offsetInBeginSection": 2244, "offsetInEndSection": 2879, "text": "In the overall population, median disease-free survival was 60\u00b75 months (95% CI 57\u00b72-not reached) for the MAGE-A3 immunotherapeutic group and 57\u00b79 months (55\u00b77-not reached) for the placebo group (hazard ratio [HR] 1\u00b702, 95% CI 0\u00b789-1\u00b718; p=0\u00b774). Of the patients who did not receive chemotherapy, median disease-free survival was 58\u00b70 months (95% CI 56\u00b76-not reached) in those in the MAGE-A3 group and 56\u00b79 months (44\u00b74-not reached) in the placebo group (HR 0\u00b797, 95% CI 0\u00b780-1\u00b718; p=0\u00b776). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27132212", "endSection": "abstract" }, { "offsetInBeginSection": 3348, "offsetInEndSection": 3523, "text": "uvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Ba", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27132212", "endSection": "abstract" } ] }, { "body": "Does protein ALEX1 contain armadillo repeats?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26464700", "http://www.ncbi.nlm.nih.gov/pubmed/20398052" ], "ideal_answer": [ "Yes,\nALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains." ], "exact_answer": "yes", "type": "yesno", "id": "5e94a8250d431b5f73000001", "snippets": [ { "offsetInBeginSection": 461, "offsetInEndSection": 622, "text": "ALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains, is expressed different in normal and carcinomas tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26464700", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 465, "text": "Arm protein lost in epithelial cancers, on chromosome X 1 (ALEX1) is a novel member of the Armadillo family which has two Armadillo repeats as opposed to more than six repeats in the classical Armadillo family members.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20398052", "endSection": "abstract" } ] }, { "body": "What disease is associated with Anticitrullinated peptide antibodies (ACPAs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32079664", "http://www.ncbi.nlm.nih.gov/pubmed/16188943", "http://www.ncbi.nlm.nih.gov/pubmed/22661643", "http://www.ncbi.nlm.nih.gov/pubmed/27696777", "http://www.ncbi.nlm.nih.gov/pubmed/31565241", "http://www.ncbi.nlm.nih.gov/pubmed/29290168", "http://www.ncbi.nlm.nih.gov/pubmed/30297575", "http://www.ncbi.nlm.nih.gov/pubmed/28826660", "http://www.ncbi.nlm.nih.gov/pubmed/29200020", "http://www.ncbi.nlm.nih.gov/pubmed/24206219", "http://www.ncbi.nlm.nih.gov/pubmed/27348081", "http://www.ncbi.nlm.nih.gov/pubmed/23440041", "http://www.ncbi.nlm.nih.gov/pubmed/27755123", "http://www.ncbi.nlm.nih.gov/pubmed/25120260", "http://www.ncbi.nlm.nih.gov/pubmed/24429169", "http://www.ncbi.nlm.nih.gov/pubmed/25997035", "http://www.ncbi.nlm.nih.gov/pubmed/26613769", "http://www.ncbi.nlm.nih.gov/pubmed/25819755", "http://www.ncbi.nlm.nih.gov/pubmed/18270852", "http://www.ncbi.nlm.nih.gov/pubmed/23716070" ], "ideal_answer": [ "nticitrullinated protein antibodies (ACPAs) are serological biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA)", "Anticitrullinated peptide antibodies (ACPAs) are associated with rheumatoid arthritis.", "Anticitrullinated peptide antibodies (ACPAs) have been shown to be associated with rheumatoid arthritis", "The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis.", "Anticitrullinated protein antibodies are found in patients with rheumatoid arthritis" ], "exact_answer": [ "rheumatoid arthritis" ], "type": "factoid", "id": "5e6e9a2fc6a8763d23000007", "snippets": [ { "offsetInBeginSection": 6, "offsetInEndSection": 95, "text": " Anticitrullinated Protein Antibodies in Patients With Long-standing Rheumatoid Arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29200020", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 196, "text": "The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29200020", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 153, "text": "nticitrullinated protein antibodies (ACPAs) are serological biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29290168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Anticitrullinated protein antibodies: origin and role in the pathogenesis of rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27755123", "endSection": "title" }, { "offsetInBeginSection": 19, "offsetInEndSection": 168, "text": "This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27755123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 368, "text": "OBJECTIVES: To increase understanding of the aetiology and pathogenesis of rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets, defined by the presence or absence of different anticitrullinated protein/peptide antibodies (ACPAs) targeting citrullinated peptides from \u03b1-enolase, vimentin, fibrinogen and collagen type II, were investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22661643", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 285, "text": "Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23716070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23716070", "endSection": "title" }, { "offsetInBeginSection": 194, "offsetInEndSection": 485, "text": "This longitudinal study investigated (1) progression from CSA to clinically detectable arthritis and (2) associations of clinical factors, serological factors (among which are anticitrullinated peptide antibodies (ACPAs)) and MRI-detected subclinical inflammation with arthritis development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26613769", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 328, "text": "Anticitrullinated peptide antibodies (ACPAs) are arguably the most likely candidate biomarker to screen for RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32079664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Anticitrullinated protein antibodies (ACPAs) constitute a class of autoantibodies found in 60-70% of patients with rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24206219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "BACKGROUND: Anticitrullinated protein antibodies (ACPAs) are serological biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA), including more severe disease and joint damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29290168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23440041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "OBJECTIVES: Anticitrullinated protein/peptide antibodies (ACPA) have an excellent diagnostic performance for rheumatoid arthriti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16188943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Anticitrullinated protein/peptide antibodies (ACPA) are highly specific for rheumatoid arthritis (RA). They", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18270852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Anticitrullinated protein antibodies (ACPAs) constitute a class of autoantibodies found in 60-70% of patients with rheumatoid arthritis (RA). The m", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24206219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Background: Anti-citrullinated peptides antibodies (ACPA) are specific for rheumatoid arthritis and have been implicated in disease patho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30297575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25997035", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 286, "text": "Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23716070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Anti-citrullinated protein/peptide antibodies (ACPAs) are detected in rheumatoid arthritis (RA) sera and because of their strict association with the disease are considered marker antibodies, probably endowed with pathogenic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25120260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "OBJECTIVES: Anti-citrullinated protein/peptide antibodies (ACPA) represent an important tool for the diagnosis of rheumatoid arthritis (RA) and the presence of multiple ACPA specificities is highly correlated with the evolution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28826660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "OBJECTIVE: Anticitrullinated protein/peptide antibodies (ACPA) are implicated in rheumatoid arthritis (RA) pathogenesis and linked to the shared ep", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24429169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25997035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Rheumatoid arthritis (RA) is an autoimmune connective tissue disease, associated with the presence of anti-citrullinated protein antibodies (ACPA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27348081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31565241", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "In antisynthetase syndrome, ACPA are associated with severe and erosive arthritis: an overlapping rheumatoid arthritis and antisynthetase syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25997035", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Introduction: Anticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31565241", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 225, "text": "Recent studies have revealed that periodontal disease (PD) is closely associated with RA and production of ACPA in RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25819755", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Association of Anti-Citrullinated Peptide Antibodies With Coronary Artery Calcification in Rheumatoid Arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27696777", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Anti-citrullinated peptide antibody (ACPA) is a highly specific autoantibody to rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25819755", "endSection": "abstract" } ] }, { "body": "What is the function of emergency granulopoiesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19414802", "http://www.ncbi.nlm.nih.gov/pubmed/29593731", "http://www.ncbi.nlm.nih.gov/pubmed/21972291", "http://www.ncbi.nlm.nih.gov/pubmed/27481851", "http://www.ncbi.nlm.nih.gov/pubmed/20581311", "http://www.ncbi.nlm.nih.gov/pubmed/23925293", "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "http://www.ncbi.nlm.nih.gov/pubmed/30021674", "http://www.ncbi.nlm.nih.gov/pubmed/24990886", "http://www.ncbi.nlm.nih.gov/pubmed/24751955", "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "http://www.ncbi.nlm.nih.gov/pubmed/25895533", "http://www.ncbi.nlm.nih.gov/pubmed/33256983", "http://www.ncbi.nlm.nih.gov/pubmed/29946048", "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "http://www.ncbi.nlm.nih.gov/pubmed/16751774" ], "ideal_answer": [ "ARIH2 encodes TRIAD1, an E3 ubiquitin ligase required for termination of emergency granulopoiesis and leukemia suppressor function in AML . The Interferon Consensus Sequence Binding Protein (Icsbp/Irf8) Is Required for Termination of Emergency GranulopOiesis . Emergency granulopsis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells (HSPCs) upon infection .", "Emergency granulopoiesis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells upon infection . It is widely considered a homoeostatic mechanism for replacing exhausted leukocytes . ARIH2 encodes TRIAD1, an E3 ubiquitin ligase required for termination of emergency granulopsis and leukemia suppressor function in MLL1 .", "During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors . Granulopoiesis is tightly regulated to meet host demands during both \"steady-state\" and \"emergency\" situations, such as infection . It promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance .", "Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Emergency granulopoiesis is a component of the innate immune response that is induced in response to infectious or inflammatory challenge. During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors.", "The function of granulopoiesis is to increase the number of neutrophils in the bone marrow to fight an infection. It's not a function, it's a function of the immune system." ], "type": "summary", "id": "5fdb8309a43ad3127800002f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 935, "text": "These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21972291", "endSection": "title" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1180, "text": "Our findings identify granulopoiesis-mediated augmentation of alloimmunity as a novel link between innate and adaptive immune responses after organ transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21972291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Granulopoiesis is tightly regulated to meet host demands during both \"steady-state\" and \"emergency\" situations, such as infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 819, "text": "After the induction of candidemia, rapid mobilization of mature granulocytes and an increase in early granulocyte precursors accompanied by cell cycle acceleration was followed by a gradual increase in granulocytes originating from the immature populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Emergency granulopoiesis is a component of the innate immune response that is induced in response to infectious or inflammatory challenge.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23925293", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1228, "text": "Failed emergency granulopoiesis in Fancc(-/-) mice was associated with excess apoptosis of HSCs and progenitor cells in the bone marrow and impaired HSC function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23925293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Systemic bacterial infection induces a hematopoietic response program termed \"emergency granulopoiesis\" that is characterized by increased de novo bone marrow (BM) neutrophil production", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24990886", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1446, "text": "Our studies demonstrate a previously undescribed role for HoxA10 in terminating emergency granulopoiesis, suggesting an important contribution by Hox proteins to the innate immune response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25895533", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 595, "text": "However, if microbial infection cannot be controlled locally, and consequently develops into a life-threatening condition, neutrophils are used up in large quantities and the haematopoietic system has to rapidly adapt to the increased demand by switching from steady-state to emergency granulopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24751955", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 751, "text": "This involves the markedly increased de novo production of neutrophils, which results from enhanced myeloid precursor cell proliferation in the bone marrow", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24751955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27481851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Emergency granulopoiesis is a very important strategy to supply efficient neutrophil number in response to infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30021674", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 543, "text": "We previously showed that C/EBP\u03b2, which is a transcription factor required for emergency granulopoiesis, plays a pivotal role at the level of hematopoietic stem/progenitor cells under stress conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 337, "text": "In fact, emergency granulopoiesis (EG), a process regulating neutrophil homeostasis in inflammatory conditions and infections, may occur improperly in leukemic conditions, leading to reduced neutrophil counts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29593731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Interferon consensus sequence-binding protein (Icsbp) is required for terminating emergency granulopoiesis, an episodic event responsible for granulocyte production in response to infections and a key component of the innate immune response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Granulocyte colony-stimulating factor (G-CSF) mediates \"emergency\" granulopoiesis during infection, a process that is mimicked by clinical G-CSF use, yet we understand little about the intracellular signaling cascades that control demand-driven neutrophil production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581311", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1256, "text": "In addition, embryos, where pax9 was functionally disrupted by injecting morpholinos, failed to increase the number of neutrophils in response to pathogenic bacteria, suggesting that Pax9 is not only essential for developmental granulopoiesis but also emergency granulopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33256983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Emergency granulopoiesis is a hematopoietic program of stem cell-driven neutrophil production used to counteract immune cell exhaustion following infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29946048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Infections and inflammation trigger neutrophilias that are supported by a hematopoietic program of accelerated granulopoiesis known as emergency granulopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19414802", "endSection": "abstract" }, { "offsetInBeginSection": 1212, "offsetInEndSection": 1430, "text": "Emergency granulopoiesis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells (HSPCs) upon infection and is widely considered a homoeostatic mechanism for replacing exhausted leukocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29946048", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 553, "text": "We show that stem cell-driven neutrophil production occurs in response to Shigella infection and requires macrophage-independent signaling by granulocyte colony-stimulating factor (Gcsf).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29946048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21972291", "endSection": "title" } ] }, { "body": "What was the predominant rotavirus genotype in the pre-vaccine era, in Australia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29790933", "http://www.ncbi.nlm.nih.gov/pubmed/30755297", "http://www.ncbi.nlm.nih.gov/pubmed/32060546" ], "ideal_answer": [ "G1P[8] was the dominant genotype in Australia in the prevaccine era (1995-2006)." ], "exact_answer": [ "G1P[8]" ], "type": "factoid", "id": "5e7667b1835f4e4777000004", "snippets": [ { "offsetInBeginSection": 789, "offsetInEndSection": 867, "text": "G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29790933", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 638, "text": "From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus-positive samples from children <5 years of age, hospitalized with acute gastroenteritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29790933", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 979, "text": "In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30755297", "endSection": "abstract" } ] }, { "body": "Missense mutations in which genes cause X-linked developmental and epileptic encephalopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33245860", "http://www.ncbi.nlm.nih.gov/pubmed/32977175" ], "ideal_answer": [ "GRIA3 missense mutation is cause of an x-linked developmental and epileptic encephalopathy. Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 also cause an X-linked developmental and epileptic encephalopathy." ], "exact_answer": [ [ "GRIA3" ], [ "FHF2", "FGF13" ] ], "type": "list", "id": "601bef4b1cb411341a000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "GRIA3 missense mutation is cause of an x-linked developmental and epileptic encephalopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32977175", "endSection": "title" }, { "offsetInBeginSection": 273, "offsetInEndSection": 1757, "text": "We report a patient carrying a hemizygous missense variant c.2359 G > A (p.Glu787Lys) inGRIA3 gene. Following a literature search, we also reviewed clinical, electrophysiological, radiological, and genetic features of 19 patients with GRIA3 mutations.RESULTS: This 26-month-old boy had developmental delay, early onset refractory myoclonic epilepsy, and non-convulsive refractory status epilepticus. In published reports, epilepsy was in 6 of 19 patients carrying different genotypes, though epilepsy and electroencephalogram features were not completely defined. Out of the 6 patients, one presented with generalized tonic-clonic seizures, two with myoclonic and clonic events (one also presented with epileptic spasms), and one with atypical absences and myoclonic jerks. Information on type of epilepsy was unavailable for 3 cases. Epilepsy onset was early in life and there was potential tendency for myoclonic/clonic events. The epilepsy was difficult to treat and prognosis is poor. Severity of ID ranged from mild to severe and was variably associated with bipolar affective disorder and autistic spectrum disorders. Other neurological features included hypotonia, asthenic body habitus with poor muscle bulk, and hyporeflexia.CONCLUSION: Our report expands knowledge on the electro-clinical and molecular spectrum of GRIA3 variants. Larger investigations will better define the prevalence of epilepsy, the epileptic phenotype, and syndromic features underlying GRIA3 variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32977175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33245860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1418, "text": "Fibroblast growth factor homologous factors (FHFs) are intracellular proteins which regulate voltage-gated sodium (Nav) channels in the brain and other tissues. FHF dysfunction has been linked to neurological disorders including epilepsy. Here, we describe two sibling pairs and three unrelated males who presented in infancy with intractable focal seizures and severe developmental delay. Whole-exome sequencing identified hemi- and heterozygous variants in the N-terminal domain of the A isoform of FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Our findings demonstrate that FHF2 variants are a cause of infantile-onset developmental and epileptic encephalopathy and underline the critical role of the FHF2A isoform in regulating Nav channel function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33245860", "endSection": "abstract" } ] }, { "body": "Does radiotherapy for cervical cancer increases risk of colon cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17971527", "http://www.ncbi.nlm.nih.gov/pubmed/24696219", "http://www.ncbi.nlm.nih.gov/pubmed/6957649" ], "ideal_answer": [ "Yes, there is epidemiological evidence to suggest that radiotherapy for cervical cancer increases risk for colon cancer." ], "exact_answer": "yes", "type": "yesno", "id": "5e3390fafbd6abf43b000060", "snippets": [ { "offsetInBeginSection": 867, "offsetInEndSection": 1021, "text": "After 8 years, the hazard ratio for developing colon cancer was 2.00 (95% CI 1.43-2.80) for women with radiation versus those without radiation treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696219", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1568, "text": "After 35 years of follow-up, the absolute risk of developing colon cancer was 6.5% for those who received radiation versus 2.5% for those without, and 3.7 versus 0.8% for rectum. The risk of colon and rectum cancer over 20 years of follow-up after radiation remained the same across three eras (1973-1980, 1981-1990, and 1991-2000). Radiation-induced second cancers of the colon and rectum may occur 8 years after radiation treatment for cervical cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696219", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1035, "text": "The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6957649", "endSection": "abstract" }, { "offsetInBeginSection": 1447, "offsetInEndSection": 1568, "text": "Radiation-induced second cancers of the colon and rectum may occur 8 years after radiation treatment for cervical cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696219", "endSection": "abstract" }, { "offsetInBeginSection": 1597, "offsetInEndSection": 1923, "text": "Cervical cancer patients treated with radiotherapy, but not those who did not receive radiotherapy, were at increased risk for all second cancers and cancers at heavily irradiated sites (colon, rectum/anus, urinary bladder, ovary, and genital sites) beyond 40 years of follow-up compared with women in the general population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17971527", "endSection": "abstract" } ] }, { "body": "List human antibody isotypes.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29382466", "http://www.ncbi.nlm.nih.gov/pubmed/29125655", "http://www.ncbi.nlm.nih.gov/pubmed/20050331", "http://www.ncbi.nlm.nih.gov/pubmed/16157351", "http://www.ncbi.nlm.nih.gov/pubmed/29684416" ], "ideal_answer": [ "IgA\nIgE\nIgG\nIgM\nIgD" ], "exact_answer": [ [ "IgA" ], [ "IgE" ], [ "IgG" ], [ "IgM" ], [ "IgD" ] ], "type": "list", "id": "5e9206f92d3121100d000008", "snippets": [ { "offsetInBeginSection": 430, "offsetInEndSection": 527, "text": "production of human antibody isotypes including immunoglobulin M (IgM), IgG1, IgG2, IgG3 and IgG4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20050331", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Human immunoglobulin D (IgD) occurs most abundantly as a membrane-bound antibody on the surface of mature B cells (mIgD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16157351", "endSection": "abstract" }, { "offsetInBeginSection": 1312, "offsetInEndSection": 1370, "text": "antibody isotypes [immunoglobulin (Ig)A, IgE, IgG and IgM]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29125655", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 907, "text": "Hybridomas generated by electrofusion produced IgG (48%), IgM (34%) and IgA (18%) antibody isotypes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382466", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 618, "text": "The antibodies investigated [IgA, IgM, total IgG (all subclasses measured together)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29684416", "endSection": "abstract" } ] }, { "body": "What is CRAO in the context of the eye?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31061190", "http://www.ncbi.nlm.nih.gov/pubmed/23470793", "http://www.ncbi.nlm.nih.gov/pubmed/29191536", "http://www.ncbi.nlm.nih.gov/pubmed/26481874", "http://www.ncbi.nlm.nih.gov/pubmed/29716787", "http://www.ncbi.nlm.nih.gov/pubmed/22827226", "http://www.ncbi.nlm.nih.gov/pubmed/27865695", "http://www.ncbi.nlm.nih.gov/pubmed/22349707", "http://www.ncbi.nlm.nih.gov/pubmed/23045923", "http://www.ncbi.nlm.nih.gov/pubmed/32398620", "http://www.ncbi.nlm.nih.gov/pubmed/20845251", "http://www.ncbi.nlm.nih.gov/pubmed/19374663", "http://www.ncbi.nlm.nih.gov/pubmed/30060907", "http://www.ncbi.nlm.nih.gov/pubmed/25473262", "http://www.ncbi.nlm.nih.gov/pubmed/32878829", "http://www.ncbi.nlm.nih.gov/pubmed/23070637", "http://www.ncbi.nlm.nih.gov/pubmed/32166539", "http://www.ncbi.nlm.nih.gov/pubmed/18542123", "http://www.ncbi.nlm.nih.gov/pubmed/28853639", "http://www.ncbi.nlm.nih.gov/pubmed/3408089", "http://www.ncbi.nlm.nih.gov/pubmed/29236169", "http://www.ncbi.nlm.nih.gov/pubmed/21620994", "http://www.ncbi.nlm.nih.gov/pubmed/24052082" ], "ideal_answer": [ "central retinal artery occlusion (CRAO) is an ophthalmological emergency, the retinal analog of a stroke.", "Central retinal artery occlusion (CRAO) is the most common central retinal artery occlusion.", "CRAO is the abbreviation for central retinal artery occlusion.", "central retinal artery occlusion (CRAO)" ], "type": "summary", "id": "5e67cce31af46fc13000001d", "snippets": [ { "offsetInBeginSection": 72, "offsetInEndSection": 112, "text": "central retinal artery occlusion (CRAO) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28853639", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 223, "text": " central retinal artery occlusion (CRAO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29191536", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 51, "text": " Central retinal artery occlusion (CRAO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29236169", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 276, "text": "Vision loss following prone surgery is most commonly attributed to direct pressure on the eye but can also be caused by central retinal artery occlusion (CRAO) in the absence of pressure on the eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32398620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Central retinal artery occlusion (CRAO) is a rare but blinding disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32878829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Central retinal artery occlusion (CRAO) causes ischemic stroke of the eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22349707", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 735, "text": "In addition, measurements were made in six patients with rhegmatogenous retinal detachment (RRD) and three patients with central retinal artery occlusion (CRAO) for comparison.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22827226", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 217, "text": " crisis. In the eye, central retinal artery occlusion (CRAO) is a rare complication in SCD, with only 1 previous report of bilateral, concurrent ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24052082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Central retinal artery occlusion (CRAO) is considered to be an acute stroke of the eye that results in profound visual loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18542123", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 342, "text": "n blinding ocular manifestations include central retinal artery occlusion (CRAO), central retinal vein occlusion (CRVO), severe vaso-occlusive retinopathy, and optic nerve involvement. Antiphos", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25473262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Acute retinal arterial ischemia, including vascular transient monocular vision loss (TMVL) and branch (BRAO) and central retinal arterial occlusions (CRAO), are ocular and systemic emergencies requiring immediate diagnosis and treatment. Guide", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29716787", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 278, "text": "ision loss following prone surgery is most commonly attributed to direct pressure on the eye but can also be caused by central retinal artery occlusion (CRAO) in the absence of pressure on the eye. C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32398620", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 396, "text": "ucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21620994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Central retinal artery occlusion (CRAO) is an ophthalmological emergency situation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20845251", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 210, "text": "ive crisis. In the eye, central retinal artery occlusion (CRAO) is a rare complication in SCD, with only 1 previous report of bilateral, conc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24052082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Central retinal artery occlusion (CRAO) is a devastating ocular emergency characterized by acute painless visual loss in the ipsilateral eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27865695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Central retinal artery occlusion (CRAO) is an ophthalmological emergency situation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20845251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Central retinal artery occlusion (CRAO) is an ophthalmic emergency and the ocular analogue of cerebral stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23470793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Central retinal artery occlusion (CRAO) is considered to be an acute stroke of the eye that results in profound visual loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18542123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "BACKGROUND: Central retinal artery occlusion (CRAO) is an ophthalmological emergency, the retinal analog ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29236169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "OPINION STATEMENT: Central retinal artery occlusion (CRAO) is an ocular emergency and is the ocular analogue ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23070637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND AND PURPOSE: Central retinal artery occlusion (CRAO) is a sudden, frequently irreversible, monocular vision loss, analogous to a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19374663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Central retinal-artery obstruction (CRAO) is a devastating complication after retrobulbar anesthesia, a procedure which was previously recommended routinely to immobilize the eye and reduce discomfort during laser surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3408089", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 725, "text": "Central retinal artery occlusion (CRAO) is a rare complication of ICAD, secondary either to haemodynamic compromise, with ocular hypoperfusion and reverse flow within the ophthalmic artery, or to thromboembolic events, in rarer cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31061190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Central retinal artery occlusion (CRAO) is an uncommon eye disorder, but one that typically produces severe and irreversible vision loss in the affected eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23045923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Central retinal artery occlusion (CRAO) is a medical emergency that, if not treated, may result in irreversible loss of vision.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30060907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND: Central retinal artery occlusion (CRAO) is an ocular emergency and most of the cases present with painless sudden persistent loss of vision in the range of counting fingers to percepti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26481874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Central retinal artery occlusion (CRAO) is a neuro-ophthalmological emergency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32166539", "endSection": "abstract" } ] }, { "body": "Is yeast fbp1 affected by glucose starvation stress?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29967244", "http://www.ncbi.nlm.nih.gov/pubmed/11238405", "http://www.ncbi.nlm.nih.gov/pubmed/27723196", "http://www.ncbi.nlm.nih.gov/pubmed/23398982", "http://www.ncbi.nlm.nih.gov/pubmed/26945040", "http://www.ncbi.nlm.nih.gov/pubmed/14762213", "http://www.ncbi.nlm.nih.gov/pubmed/30670704" ], "ideal_answer": [ "The chromatin configuration is altered into an accessible state within 290\u2009bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation . We investigated the mechanisms by which chromatin is reconstituted .", "Histone Chaperone Asf1 is required for the establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression . Chromatin is reconstituted in the fission yeast Schizoaccharombe pombefbp1 gene, which is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions .", "Yes. transcription factors in Saccharomyces cerevisiae fbp1 and fbp2 are involved in the response to glucose starvation stress.", "The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK)", "Yes. In Saccharomyces cerevisiae, fbp1 expression is affected by glucose starvation and is increased under glucose starvation stress.", "The Schizosaccharomyces pombe fbp1 gene is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions. The Schizosaccharomyces pombe fbp1 gene encodes fructose-1,6-bisphosphatase.", "The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK).", "Yes. In Saccharomyces cerevisiae, transcriptional responses to glucose starvation are mediated by the F-box protein fbp1. Ace1 mediates glucose-induced gene expression in cells exposed to stressful levels of glucose, whereas fBP1 activates a subset of genes under glucose-free conditions.", "Yes. The yeast fbp1 gene, which encodes fructose-1,6,bis-bis-phosphatase, is transcriptionally repressed by the CAMP-dependent protein kinase (PKA) and transcriptionally suppressed by the mitogen-activated Protein Kinase (MAPK). It is not affected by glucose starvation stress, but it is affected by the stress of starvation.", "Yes. In Saccharomyces cerevisiae, transcriptional responses to glucose starvation are mediated by two distal enhancer elements, fbp1 and fbp2.", "Yes. transcription of yeast fbp1 is increased in response to glucose starvation stress." ], "exact_answer": "yes", "type": "yesno", "id": "5fe31321a43ad3127800004b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Histone Chaperone Asf1 Is Required for the Establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967244", "endSection": "title" }, { "offsetInBeginSection": 523, "offsetInEndSection": 709, "text": "chromatin is reconstituted in the fission yeast Schizosaccharomyces pombefbp1 gene, which is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11238405", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 475, "text": "Antisense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 265, "text": "In fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26945040", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 458, "text": "We herein show that the chromatin configuration is altered into an accessible state within 290\u2009bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30670704", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 1046, "text": "Cation stress and glucose starvation selectively caused chromatin structure alteration around CRE-like sequences in cta3(+) and fbp1(+) promoters, respectively, in correlation with transcriptional activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14762213", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 462, "text": " herein show that the chromatin configuration is altered into an accessible state within 290\u2009bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation. Chr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30670704", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 268, "text": "fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1). At", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26945040", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 481, "text": "isense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation. Here,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 475, "text": "locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1262, "text": "Furthermore, fbp1-as and antisense RNA at other stress-responsive loci are promptly degraded via the cotranslational nonsense-mediated decay (NMD) pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1377, "text": "These results suggest NMD may potentiate the swift disappearance of antisense RNAs in response to cellular stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Antisense RNA has emerged as a crucial regulator of opposite-strand protein-coding genes in the long noncoding RNA (lncRNA) category, but little is known about their dynamics and decay process in the context of a stress response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723196", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 661, "text": "xic growth. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23398982", "endSection": "abstract" } ] }, { "body": "What does csDMARD stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30629813" ], "ideal_answer": [ "csDMARDS are conventional synthetic disease-modifying antirheumatic drugs." ], "exact_answer": [ "conventional synthetic disease-modifying antirheumatic drug" ], "type": "factoid", "id": "602598301cb411341a0000b0", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 370, "text": "To determine whether intensive combinations of conventional synthetic disease-modifying antirheumatic drugs (csDMARDS) achieve similar clinical benefits more cheaply than high-cost biologics such as tumor necrosis factor inhibitors (TNFi) in patients with active rheumatoid arthritis (RA) whose illness has failed to respond to methotrexate and another DMARD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30629813", "endSection": "abstract" } ] }, { "body": "What is caused by SCUBE2 loss-of-function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25639508" ], "ideal_answer": [ "Scube2 (-/-) caused defective endochondral bone formation and impaired Ihh-mediated chondrocyte differentiation and proliferation as well as osteoblast differentiation of -/- bone-marrow mesenchymal stromal-cell cultures.", "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation of -/--marrow cells cultures.", "Loss-of-function of SCUBE2 causes loss of osteoblast differentiation, bone formation and endochondral bone formation. Loss of the hedgehog signaling pathway plays an important role in skeletal development.", "Loss-of-function mutations of SCUBE2 lead to premature differentiation of osteoblast differentiation, bone formation and endochondral bone formation. Down-regulation of hedgehog signaling promotes the formation of osteoblasts, adipogenesis.", "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation of -/- marrow-marrow.", "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation of -/--marrow.", "Loss-of-function of SCUBE2 causes loss of function, disruption of osteoblast differentiation, bone formation and endochondral bone formation.", "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation.", "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation.", "Loss-of-function mutations of SCUBE2 cause loss of osteoblast differentiation, bone formation and endochondral bone formation. Loss of hedgehog activity leads to premature differentiation of mesenchymal stem cells and induces apoptosis of chondrocyte precursor cells." ], "exact_answer": [ [ "Defective endochondral bone formation" ], [ "Impaired Ihh-mediated chondrocyte differentiation and proliferation" ], [ "Osteoblast differentiation of -/- bone-marrow mesenchymal stromal-cell cultures" ] ], "type": "list", "id": "601bd7d41cb411341a000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Disruption of Scube2 Impairs Endochondral Bone Formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25639508", "endSection": "title" }, { "offsetInBeginSection": 546, "offsetInEndSection": 1331, "text": "In this study, we first showed that as compared with SCUBE1 or SCUBE3, SCUBE2 is the most potent modulator of IHH signaling in vitro. In addition, gain and loss-of-function studies demonstrated that SCUBE2 exerted an osteogenic function by enhancing Ihh-stimulated osteoblast differentiation in the mouse mesenchymal progenitor cells. Consistent with these in vitro studies and the prominent roles of Ihh in coordinating skeletogenesis, genetic ablation of Scube2 (-/-) caused defective endochondral bone formation and impaired Ihh-mediated chondrocyte differentiation and proliferation as well as osteoblast differentiation of -/- bone-marrow mesenchymal stromal-cell cultures. Our data demonstrate that Scube2 plays a key regulatory role in Ihh-dependent endochondral bone formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25639508", "endSection": "abstract" }, { "offsetInBeginSection": 680, "offsetInEndSection": 880, "text": "In addition, gain and loss-of-function studies demonstrated that SCUBE2 exerted an osteogenic function by enhancing Ihh-stimulated osteoblast differentiation in the mouse mesenchymal progenitor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25639508", "endSection": "abstract" } ] }, { "body": "Is Semagacestat effective for Alzheimer's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "http://www.ncbi.nlm.nih.gov/pubmed/23785331", "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "http://www.ncbi.nlm.nih.gov/pubmed/23196551", "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "http://www.ncbi.nlm.nih.gov/pubmed/25292430", "http://www.ncbi.nlm.nih.gov/pubmed/21149978", "http://www.ncbi.nlm.nih.gov/pubmed/22087836", "http://www.ncbi.nlm.nih.gov/pubmed/28978478", "http://www.ncbi.nlm.nih.gov/pubmed/21501112", "http://www.ncbi.nlm.nih.gov/pubmed/26064192" ], "ideal_answer": [ "No. In a placebo controlled clinical trial, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. The trial was terminated due to unexpected aggravation of cognitive deficits and side effects." ], "exact_answer": "no", "type": "yesno", "id": "5e4b64516d0a277941000029", "snippets": [ { "offsetInBeginSection": 173, "offsetInEndSection": 403, "text": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28978478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1415, "text": "CONCLUSION: In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "INTRODUCTION: The negative efficacy study examining the \u03b3-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26064192", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 398, "text": "A clinical trial with the wide-spectrum \u03b3-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all \u03b3-secretases causes serious toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25292430", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 1147, "text": "ESULTS: Semagacestat treatment was associated with increased reporting of suspected Notch-related adverse events (gastrointestinal, infection, and skin cancer related). Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983746", "endSection": "abstract" }, { "offsetInBeginSection": 2360, "offsetInEndSection": 2533, "text": "CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1208, "text": "RESULTS: The trial was terminated before completion on the basis of a recommendation by the data and safety monitoring board.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 2136, "text": "The ADAS-cog scores worsened in all three groups (mean change, 6.4 points in the placebo group, 7.5 points in the group receiving 100 mg of the study drug, and 7.8 points in the group receiving 140 mg; P=0.15 and P=0.07, respectively, for the comparison with placebo). The ADCS-ADL scores also worsened in all groups (mean change at week 76, -9.0 points in the placebo group, -10.5 points in the 100-mg group, and -12.6 points in the 140-mg group; P=0.14 and P<0.001, respectively, for the comparison with placebo). Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23883379", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 640, "text": "Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23785331", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The recent failure of semagacestat in two large Phase III studies questions the value of \u03b3-secretase inhibitors in treating Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21149978", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 646, "text": "ntly disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo. Since", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23785331", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 896, "text": "ts from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Furthermore, sem", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23196551", "endSection": "abstract" }, { "offsetInBeginSection": 1077, "offsetInEndSection": 1293, "text": "rge Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effect of the drug. These detrimental ef", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22087836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567808", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 402, "text": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28978478", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1117, "text": "However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent \u03b3-secretase inhibitor, raise the possibility that targeting A\u03b2 may not be clinically efficacious in AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21501112", "endSection": "abstract" } ] }, { "body": "List enzymes that removes histone modifications.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29413177", "http://www.ncbi.nlm.nih.gov/pubmed/30344952", "http://www.ncbi.nlm.nih.gov/pubmed/21336812" ], "ideal_answer": [ "Histone deacetylases\nLysine Specific Demethylases" ], "exact_answer": [ [ "Histone deacetylases", "HDAC" ], [ "Lysine Specific Demethylases", "LSD" ] ], "type": "list", "id": "5e9209792d3121100d00000b", "snippets": [ { "offsetInBeginSection": 327, "offsetInEndSection": 432, "text": ", Lysine Specific Demethylases (LSD) removes methylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30344952", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 445, "text": "A family of enzymes, namely histone deacetylases (HDACs), removes these PTMs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29413177", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 315, "text": " Histone deacetylases (HDACs), a specific epigenetic group of enzymes, dynamically and reversibly removes acetyl groups from histone tails projecting from the nucleosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21336812", "endSection": "abstract" } ] }, { "body": "Roughly how many base pairs are in the human mitochondrial genome or mtDNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18623076", "http://www.ncbi.nlm.nih.gov/pubmed/29121011", "http://www.ncbi.nlm.nih.gov/pubmed/19591276", "http://www.ncbi.nlm.nih.gov/pubmed/27814641", "http://www.ncbi.nlm.nih.gov/pubmed/1528004", "http://www.ncbi.nlm.nih.gov/pubmed/8884568", "http://www.ncbi.nlm.nih.gov/pubmed/16406745", "http://www.ncbi.nlm.nih.gov/pubmed/24780559", "http://www.ncbi.nlm.nih.gov/pubmed/10733641", "http://www.ncbi.nlm.nih.gov/pubmed/2517473", "http://www.ncbi.nlm.nih.gov/pubmed/22142616", "http://www.ncbi.nlm.nih.gov/pubmed/28756246", "http://www.ncbi.nlm.nih.gov/pubmed/17827523", "http://www.ncbi.nlm.nih.gov/pubmed/18638794", "http://www.ncbi.nlm.nih.gov/pubmed/22120174", "http://www.ncbi.nlm.nih.gov/pubmed/28551783" ], "ideal_answer": [ "The mitochondrial genome, mtDNA, is 16569 base pairs.", "The number of base pairs in the human mitochondrial genome (mhl) is currently estimated at 16569." ], "exact_answer": [ "16569 bps" ], "type": "factoid", "id": "5e61425e1af46fc13000000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "The 16569 base pairs of the mitochondrial DNA ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2517473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND: Somatic mutations of mitochondrial DNA (mtDNA) are increasingly being recognized in many human cancers, but automated sequencing of 16.5 kb of DNA poses an onerous task.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17827523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The human mitochondrial genome consists of a multicopy, circular dsDNA molecule of 16,569 base pairs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18623076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "In addition to the 3 billion base pair nuclear genome, each human cell contains thousands of copies of a small, 16.5 kb circular molecule of double stranded DNA: mitochondria have their own DNA (mtDNA) which generally accounts for only 1% of the total cellular nucleic acid content. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10733641", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 658, "text": "ntrast, human cells contain hundreds to thousands of copies of a ca.16 kB mtDNA genome tightly packed with 13 protein-coding genes along with rRNA and tRNA genes required for their expression. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22142616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Human mitochondria harbor an essential, high copy number, 16,569 base pair, circular DNA genome that encodes 13 gene products required for electron transport and oxidative phosphorylation. M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24780559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The small (16,569 base pair) human mitochondrial genome plays a significant role in cell metabolism and homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27814641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Human mitochondria harbor an essential, high copy number, 16,569 base pair, circular DNA genome that encodes 13 gene products required for electron transport and oxidative phosphorylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24780559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Mammalian mitochondrial DNA (mtDNA) is a circular double-stranded DNA genome of ~16.5 kilobase pairs (kb) that encodes 13 catalytic proteins of the ATP-producing oxidative phosphorylation system (OXPHOS), and the rRNAs and tRNAs required for the translation of the mtDNA transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22120174", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 314, "text": "Mitochondrial DNA (mtDNA) is a circular, double-stranded, 16,569-base paired DNA containing 37 genes: 13 proteins of the mitochondrial respiratory chain, two ribosomal RNAs (rRNAs; 12S and 16S), and 22 transfer RNAs (tRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28551783", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 450, "text": "The mitochondrial genome of humans and most vertebrates is approximately 16.5kbp, double-stranded, circular, with few non-coding bases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28756246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "In humans, mitochondrial DNA (mtDNA) is a 16,569-bp double-stranded circular molecule, encoding 37 genes, and is exclusively transmitted from the mother.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19591276", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 312, "text": "They are maternally inherited and in humans contain a 16,569-base-pair circular genome (mtDNA) encoding 37 genes required for oxidative phosphorylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29121011", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 242, "text": "Mitochondrial DNA mutations range from single base pair changes in the 16.5 kilobase pair genome up to large deletions and rearrangements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8884568", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 653, "text": "In contrast, human cells contain hundreds to thousands of copies of a ca.16 kB mtDNA genome tightly packed with 13 protein-coding genes along with rRNA and tRNA genes required for their expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22142616", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 363, "text": "For comprehensive mutation scanning of the whole 16.569 bp human mitochondrial genome, we developed a set of 67 primer pairs defining overlapping PCR fragments that are well suited for heteroduplex analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16406745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Human mitochondrial DNA, the 25th chromosome, is a 16 569 base pair long circular molecule, that encoders a variety of genes for the translational machinery of the mitochondrion, as well as 13 structural proteins, that are all subunits of the respiratory chain (RC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18638794", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 241, "text": "Mitochondrial DNA mutations range from single base changes in the 16.5 kilobase-pair genome up to large deletions and rearrangements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1528004", "endSection": "abstract" } ] }, { "body": "Do nematodes contain a CTCF gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "http://www.ncbi.nlm.nih.gov/pubmed/17442748", "http://www.ncbi.nlm.nih.gov/pubmed/29385718" ], "ideal_answer": [ "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans.", "Insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans . The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode yeast . Our findings show that C.TCF and possibly chromatin insulation are present in basal nemathews .", "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes.", "We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode.", "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode." ], "exact_answer": "yes", "type": "yesno", "id": "5e9eba150d431b5f73000005", "snippets": [ { "offsetInBeginSection": 1157, "offsetInEndSection": 1357, "text": "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 983, "text": "The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17442748", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1147, "text": " show that three ZF proteins from three basal nematodes cluster together with known CTCF proteins whereas no zinc finger protein of C. elegans and other derived nematodes does so.CO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 659, "text": "SULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 989, "text": "of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier st", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385718", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1254, "text": "LUSION: Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1361, "text": "uggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 658, "text": "ESULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1359, "text": " suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1147, "text": "e show that three ZF proteins from three basal nematodes cluster together with known CTCF proteins whereas no zinc finger protein of C. elegans and other derived nematodes does so.CO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 964, "text": "o investigate the pattern of CTCF occurrence in nematodes, we performed phylogenetic analysis with the ZF protein sets of completely sequenced nematodes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1252, "text": "r findings show that CTCF and possibly chromatin insulation are present in basal nematodes. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1631, "text": " propose a switch in the regulation of gene expression during nematode evolution, from the common vertebrate and insect type involving distantly acting regulatory elements and chromatin insulation to a so far poorly characterised mode present in more derived nematodes. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 504, "text": "We therefore searched in nematodes for orthologs of proteins that are involved in chromatin insulation.R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 963, "text": "The unique secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385718", "endSection": "abstract" } ] }, { "body": "Is tocilizumab a csDMARD?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31969328" ], "ideal_answer": [ "No, tocilizumab is a biological DMARD (bDMARD)." ], "exact_answer": "no", "type": "yesno", "id": "60259fe91cb411341a0000b3", "snippets": [ { "offsetInBeginSection": 730, "offsetInEndSection": 1251, "text": "The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31969328", "endSection": "abstract" } ] }, { "body": "What is caused by heterozygous lamin B1 and lamin B2 variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33033404", "http://www.ncbi.nlm.nih.gov/pubmed/32910914" ], "ideal_answer": [ "Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.", "Heterozygous lamin B1 and Lamin B2 variants cause primary microcephaly and define a novel laminopathy.", "Microcephaly is a rare autosomal recessive disorder caused by heterozygous lamin B1 and Lamin B2 variants.", "Heterozygous lamin B1 and Lamin B2 variants cause primary microcephaly and define a novel laminopathy", "Heterozygous lamin B1 and laminB2 variants cause primary microcephaly and define a novel laminopathy." ], "exact_answer": [ "Primary microcephaly" ], "type": "factoid", "id": "601bfa531cb411341a000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33033404", "endSection": "title" }, { "offsetInBeginSection": 240, "offsetInEndSection": 1362, "text": "Phenotypes resulting from variants in LMNB1 and LMNB2 have been much less clearly defined.METHODS: We investigated exome and genome sequencing from the Deciphering Developmental Disorders Study and the 100,000 Genomes Project to identify novel microcephaly genes.RESULTS: Starting from a cohort of patients with extreme microcephaly, 13 individuals with heterozygous variants in the two human B-type lamins were identified. Recurrent variants were established to be de novo in nine cases and shown to affect highly conserved residues within the lamin \u0251-helical rod domain, likely disrupting interactions required for higher-order assembly of lamin filaments.CONCLUSION: We identify dominant pathogenic variants in LMNB1 and LMNB2 as a genetic cause of primary microcephaly, implicating a major structural component of the nuclear envelope in its etiology and defining a new form of laminopathy. The distinct nature of this lamin B-associated phenotype highlights the strikingly different developmental requirements for lamin paralogs and suggests a novel mechanism for primary microcephaly warranting future investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33033404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33033404", "endSection": "title" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1137, "text": "identify dominant pathogenic variants in LMNB1 and LMNB2 as a genetic cause of primary microcephaly, implicating a major structural component of the nuclear envelope in its etiology and defining a new form of laminopathy. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33033404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32910914", "endSection": "title" } ] }, { "body": "What is the risk for secondary cancer after proton beam therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10394397", "http://www.ncbi.nlm.nih.gov/pubmed/21767176", "http://www.ncbi.nlm.nih.gov/pubmed/29106564", "http://www.ncbi.nlm.nih.gov/pubmed/28603224", "http://www.ncbi.nlm.nih.gov/pubmed/32733794", "http://www.ncbi.nlm.nih.gov/pubmed/24180282", "http://www.ncbi.nlm.nih.gov/pubmed/27534798", "http://www.ncbi.nlm.nih.gov/pubmed/33008412", "http://www.ncbi.nlm.nih.gov/pubmed/11023601", "http://www.ncbi.nlm.nih.gov/pubmed/25861886", "http://www.ncbi.nlm.nih.gov/pubmed/28366554", "http://www.ncbi.nlm.nih.gov/pubmed/20514614", "http://www.ncbi.nlm.nih.gov/pubmed/27789564", "http://www.ncbi.nlm.nih.gov/pubmed/26605679", "http://www.ncbi.nlm.nih.gov/pubmed/19427561", "http://www.ncbi.nlm.nih.gov/pubmed/27165972", "http://www.ncbi.nlm.nih.gov/pubmed/30241747", "http://www.ncbi.nlm.nih.gov/pubmed/26636040", "http://www.ncbi.nlm.nih.gov/pubmed/28004469", "http://www.ncbi.nlm.nih.gov/pubmed/22149823", "http://www.ncbi.nlm.nih.gov/pubmed/19305036" ], "ideal_answer": [ "Proton beam therapy is associated with lower risk of secondary cancer when compared to other radiation therapy approaches. It allows excellent dose localization by administration of a high dose to the tumor while minimizing damage to surrounding normal tissues. Therefore it is more commonly used in children." ], "type": "summary", "id": "5e339202fbd6abf43b000062", "snippets": [ { "offsetInBeginSection": 1362, "offsetInEndSection": 1500, "text": "In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27789564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004469", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1403, "text": "No malignant secondary tumors occurred within the irradiated field. The 10- and 20-year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004469", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 827, "text": "However, treatment-related toxicities have also occurred, particularly for radiotherapy, after which secondary cancer, reduced function of irradiated organs, and retarded growth are significant problems. Proton beam therapy (PBT) is a particle radiotherapy with excellent dose localization that permits treatment of liver and lung cancer by administration of a high dose to the tumor while minimizing damage to surrounding normal tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28603224", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 441, "text": "Notably, proton beam therapy is very useful for pediatric cancer; since the pediatric radiation dose to normal tissues should be reduced as much as possible because of the effect of radiation on growth, intellectual development, endocrine organ function and secondary cancer development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27534798", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1418, "text": "After proton beam therapy (low-LET radiation), the risk of secondary cancer induction, relative to photons, can be divided by a factor of 3, due to the reduction of integral dose (as an average). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10394397", "endSection": "abstract" }, { "offsetInBeginSection": 1546, "offsetInEndSection": 1704, "text": "However, after heavy-ion beam therapy, the risk should be divided by 3, as after proton therapy due to the excellent physical selectivity of the irradiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10394397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Proton beam therapy (PT) offers improved sparing of normal tissue, thus potentially reducing the risk for treatment related late sequelae and induction of secondary cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20514614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "INTRODUCTION: The concern of secondary cancer induction and normal tissue complications have motivated a more frequent use of protons in radiotherapy (RT) of children. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21767176", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 486, "text": "However, activation, neutron production, and the associated secondary cancer risk in proton beam should be an important consideration which is evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22149823", "endSection": "abstract" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1105, "text": "RESULTS: In all evaluated organs, the mean dose in PBT was 20-80% of that in CRT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24180282", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1356, "text": "The risk of secondary cancer in PBT was 24-83% of that in CRT for five organs, but 121% of that in CRT for pancreas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24180282", "endSection": "abstract" }, { "offsetInBeginSection": 1557, "offsetInEndSection": 1718, "text": "Assessments of secondary cancer risk showed that PBT reduces the risk of secondary cancer in most organs, whereas IMRT is associated with a higher risk than CRT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24180282", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 362, "text": "A recent study suggested reduced secondary cancer and other late toxicities after proton beam therapy (PBT) due to dosimetric advantages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27165972", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1417, "text": "After proton beam therapy (low-LET radiation), the risk of secondary cancer induction, relative to photons, can be divided by a factor of 3, due to the reduction of integral dose (as an average).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10394397", "endSection": "abstract" }, { "offsetInBeginSection": 1067, "offsetInEndSection": 1294, "text": "The incidence of secondary malignancies after proton beam therapy is low but not negligible, therefore, it must be taken into account when planning a treatment as secondary tumors may present with a highly aggressive behaviour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25861886", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1686, "text": "We show that compared with photon therapy, proton therapy markedly reduces the risk of secondary malignancies and for equivalent dosing regimens achieves better tumour control as well as a reduced primary recurrence outcome, especially within a hypo-fractionated regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29106564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Purpose: Proton radiotherapy (PRT) is potentially associated with a lower risk for secondary malignancies due to a decreased integral dose to the surrounding organs at risk (OARs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32733794", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1403, "text": "Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28004469", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 828, "text": "The total lifetime risk of second cancer due exclusively to stray radiation was 1.5% for the passively scattered treatment versus 0.8% for the scanned proton beam treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19305036", "endSection": "abstract" }, { "offsetInBeginSection": 1897, "offsetInEndSection": 2055, "text": "In general, the risk for developing a second malignancy in out-of-field organs for PBS remains much lower compared to PPT even if apertures are being applied.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26605679", "endSection": "abstract" }, { "offsetInBeginSection": 1638, "offsetInEndSection": 1749, "text": "CONCLUSIONS: PBS PT is associated to significant SCR reduction in BC patients compared to photon radiotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33008412", "endSection": "abstract" }, { "offsetInBeginSection": 1579, "offsetInEndSection": 1762, "text": "Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30241747", "endSection": "abstract" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1454, "text": "CONCLUSIONS: When considering exposure to primary and secondary radiation, proton therapy can reduce the risk of an SMN in prostate patients compared with contemporary IMRT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19427561", "endSection": "abstract" }, { "offsetInBeginSection": 1394, "offsetInEndSection": 1601, "text": "CONCLUSION: The findings of this study indicate that the risks of radiation-induced secondary cancers after radiosurgery of liver metastases may be reduced, if IMPT is used instead of photon-beam based SBRT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28366554", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1127, "text": "Clinical data are emerging supporting the lower incidence of secondary malignancies after PRT compared with historical photon data, though longer follow-up in proton treated cohorts is awaited.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26636040", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1536, "text": "However, proton treatment can result in a lower cancer incidence than photon treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11023601", "endSection": "abstract" } ] }, { "body": "List the essential aminoacids.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28089725", "http://www.ncbi.nlm.nih.gov/pubmed/6620854", "http://www.ncbi.nlm.nih.gov/pubmed/23477202", "http://www.ncbi.nlm.nih.gov/pubmed/11347201" ], "ideal_answer": [ "Leucine\r\nIsoleucine\r\nValine \r\nTryptophan\r\nCysteine\r\nMethionine\r\nLysine\r\nPhenylalanine" ], "exact_answer": [ [ "Leucine" ], [ "Isoleucine" ], [ "Valine" ], [ "Tryptophan" ], [ "Cysteine" ], [ "Methionine" ], [ "Lysine" ], [ "Phenylalanine" ] ], "type": "list", "id": "5e92021a2d3121100d000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Leucine, isoleucine and valine are essential aminoacids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28089725", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 341, "text": "high proportion of essential aminoacids (tryptophan and cysteine)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23477202", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 183, "text": "Essential aminoacids methionine and lysine can be found in significantly lower amounts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11347201", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 241, "text": " essential aminoacids, the calcium-ketoacids of valine, leucine, isoleucine, and phenylalanine, and the calcium-hydroxyacid of methionine, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6620854", "endSection": "abstract" } ] }, { "body": "What does Retapamulin treat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20066388", "http://www.ncbi.nlm.nih.gov/pubmed/19344241", "http://www.ncbi.nlm.nih.gov/pubmed/16957433", "http://www.ncbi.nlm.nih.gov/pubmed/28491950", "http://www.ncbi.nlm.nih.gov/pubmed/18416589", "http://www.ncbi.nlm.nih.gov/pubmed/18725451", "http://www.ncbi.nlm.nih.gov/pubmed/24935401", "http://www.ncbi.nlm.nih.gov/pubmed/28874907", "http://www.ncbi.nlm.nih.gov/pubmed/18973410", "http://www.ncbi.nlm.nih.gov/pubmed/22777229", "http://www.ncbi.nlm.nih.gov/pubmed/23793314", "http://www.ncbi.nlm.nih.gov/pubmed/23837927", "http://www.ncbi.nlm.nih.gov/pubmed/25396674", "http://www.ncbi.nlm.nih.gov/pubmed/18041900", "http://www.ncbi.nlm.nih.gov/pubmed/20941943", "http://www.ncbi.nlm.nih.gov/pubmed/21191403", "http://www.ncbi.nlm.nih.gov/pubmed/25250996", "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "http://www.ncbi.nlm.nih.gov/pubmed/16940066", "http://www.ncbi.nlm.nih.gov/pubmed/18341664", "http://www.ncbi.nlm.nih.gov/pubmed/17350985" ], "_body": "What does Retapamulin treat?", "ideal_answer": [ "Retapamulin is a small molecule covalently binding and inhibiting the bacterium Staphylococcus aureus (MRSA).", "Retapamulin is used to treat topical bacterial infections with both methicillin-susceptible and resistant S. aureus and streptococcus infections.", "Retapamulin is an antiviral medication used in the treatment of methicillin-resistant Staphylococcus aureus." ], "exact_answer": [ "bacterial infections" ], "type": "factoid", "id": "5e5e508b1af46fc13000000c", "snippets": [ { "offsetInBeginSection": 426, "offsetInEndSection": 678, "text": " the current study, we investigated the relationship between pleuromutilins, including valnemulin, tiamulin, and retapamulin, and 13 other antibiotics representing different mechanisms of action, against methicillin-susceptible and -resistant S. aureus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28874907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Clinical and bacteriological efficacy of twice daily topical retapamulin ointment 1% in the management of impetigo and other uncomplicated superficial skin infections", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28491950", "endSection": "title" }, { "offsetInBeginSection": 268, "offsetInEndSection": 475, "text": "To determine clinical and bacteriological efficacy of retapamulin ointment 1% in treatment of patients with cutaneous bacterial infections caused by methicillin-resistant S. aureus (MRSA) and other bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28491950", "endSection": "abstract" }, { "offsetInBeginSection": 1743, "offsetInEndSection": 1855, "text": " Fusidic acid, mupirocin, and retapamulin cover methicillin-susceptible S. aureus and streptococcal infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25250996", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 857, "text": "Treatment includes topical antibiotics such as mupirocin, retapamulin, and fusidic acid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25250996", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 259, "text": "topical retapamulin ointment 1% versus oral linezolid in the treatment of secondarily infected traumatic lesions and impetigo due to methicillin-resistant Staphylococcus aureus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25396674", "endSection": "title" }, { "offsetInBeginSection": 10, "offsetInEndSection": 293, "text": " To evaluate the clinical and bacteriological efficacy of topical retapamulin ointment 1% versus oral linezolid in the treatment of patients with secondarily infected traumatic lesions (SITLs; excluding abscesses) or impetigo due to methicillin-resistant Staphylococcus aureus (MRSA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25396674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Retapamulin is a semisynthetic pleuromutilin derivative being developed as a topical antibiotic for treating bacterial infections of the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16940066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVES: Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "endSection": "abstract" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1409, "text": "Retapamulin appears to be a much needed antimicrobial option for treating the AD population due to their common carriage of bacterial pathogens and frequency of infectious complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20066388", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 435, "text": "Retapamulin belongs to a newly developed class of antibiotics for the treatment of uncomplicated skin infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18341664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Retapamulin: what is the role of this topical antimicrobial in the treatment of bacterial infections in atopic dermatitis?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20066388", "endSection": "title" }, { "offsetInBeginSection": 859, "offsetInEndSection": 980, "text": "In vitro, retapamulin is highly potent against S. aureus and has a lower propensity to develop resistance than mupirocin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20941943", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1272, "text": "(twice-daily) dosing of retapamulin is highly effective against impetigo due to methicillin- susceptible S. aureus and Streptococcus pyogenes and may play an important role in limiting the development of resistance against systemic agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20941943", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 858, "text": "In 2007, retapamulin was the first agent for human use approved in the pleuromutilin class of antibacterials in the United States (U.S.), and is the first topical antibacterial indicated to treat impetigo in over 20 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20941943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Retapamulin: an antibacterial with a novel mode of action in an age of emerging resistance to Staphylococcus aureus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20941943", "endSection": "title" }, { "offsetInBeginSection": 315, "offsetInEndSection": 458, "text": "tion. Retapamulin 1% ointment is a unique topical antibiotic formulation that may be a suitable option for the treatment of clinically infected", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777229", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1107, "text": "e, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21191403", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 916, "text": "dic acid and mupirocin treatment for 3 days reduced the bacterial loads by 2.5, 2.9 and 2.0 log(10) CFU, respectively, and treatment for 6 days by 5.0, 4.2 and 5.1 log(10) CFU, respectively, compared with non-treated controls (P < 0.001). Systemic treatment with line", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23837927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Topical retapamulin (Altabax, Altargo) is the first pleuromutilin antibacterial approved for the treatment of uncomplicated superficial skin infections caused by Staphylococcus aureus (excluding meticillin-resistant S. aureus [MRSA]) and Streptococcus pyogenes in patients aged > or = 9 months. In the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18416589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Topical retapamulin (Altabax, Altargo) is the first pleuromutilin antibacterial approved for the treatment of uncomplicated superficial skin infections caused by Staphylococcus aureus (excluding methicillin-resistant S. aureus [MRSA]) and Streptococcus pyogenes in patients aged > or = 9 months. In the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18973410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Retapamulin, the first pleuromutilin antimicrobial agent approved for the topical treatment of skin infections in humans, was tested against 987 clinical isolates representing 30 species and/or resistance groups. MIC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18725451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "INTRODUCTION: Retapamulin is a novel, topical antibacterial of the pleuromutilin class in development for the treatment of secondarily infected traumatic lesions ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16957433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Retapamulin: a new topical antibiotic for the treatment of uncomplicated skin infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "title" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1186, "text": "Further, the clinical efficacy and safety profile of retapamulin was comparable to that of commonly used oral and topical antibiotics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1493, "text": "As a 1% ointment, retapamulin has been approved in the United States for the treatment of impetigo and in Europe for the shortterm treatment of impetigo and infected small lacerations, abrasions and sutured wounds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Retapamulin is the first agent in the new pleuromutilin class of antibacterials to become commercially available for clinical use in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 1051, "text": "In clinical efficacy trials involving pediatric and adult patients who received retapamulin twice daily for five days, retapamulin was highly effective in the treatment of impetigo, secondarily infected traumatic lesions and secondarily infected dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 663, "text": "In preclinical studies, retapamulin demonstrated pronounced in vitro activity against staphylococcal, streptococcal and anaerobic Gram-positive clinical isolates associated with skin and skin structure infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 254, "text": "Retapamulin acts as a potent inhibitor of bacterial protein synthesis and has a unique mode of antibiotic action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18389088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "INTRODUCTION: Retapamulin is a novel, topical antibacterial of the pleuromutilin class in development for the treatment of secondarily infected traumatic lesion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16957433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Retapamulin is a new topical pleuromutilin antibiotic for the treatment of skin and skin-structure infections, including impetigo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19344241", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "INTRODUCTION: Retapamulin, a topical pleuromutilin that selectively inhibits bacterial protein synthesis, is approved for treatment of impetigo and secondarily infected traumatic lesions in adults and in children older than 9 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24935401", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 376, "text": "Retapamulin is a newer topical agent of pleuromutilin class approved by the Food and Drug Administration for treatment of impetigo in children and has been recently made available in the Indian market.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23793314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Retapamulin: a semisynthetic pleuromutilin compound for topical treatment of skin infections in adults and children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18041900", "endSection": "title" }, { "offsetInBeginSection": 309, "offsetInEndSection": 450, "text": "flammation. Retapamulin 1% ointment is a unique topical antibiotic formulation that may be a suitable option for the treatment of clinically ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22777229", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "OBJECTIVES: Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "In vitro activity against anaerobes of retapamulin, a new topical antibiotic for treatment of skin infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17350985", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "Topical retapamulin (Altabax, Altargo) is the first pleuromutilin antibacterial approved for the treatment of uncomplicated superficial skin infections caused by Staphylococcus aureus (excluding methicillin-resistant S. aureus [MRSA]) and Streptococcus pyogenes in patients aged > or = 9 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18973410", "endSection": "abstract" } ] }, { "body": "Which histone mark distinguishes active from inactive enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27851968", "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "http://www.ncbi.nlm.nih.gov/pubmed/15448640", "http://www.ncbi.nlm.nih.gov/pubmed/22920947", "http://www.ncbi.nlm.nih.gov/pubmed/28732206", "http://www.ncbi.nlm.nih.gov/pubmed/24565409", "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "http://www.ncbi.nlm.nih.gov/pubmed/21160473", "http://www.ncbi.nlm.nih.gov/pubmed/25984238", "http://www.ncbi.nlm.nih.gov/pubmed/26305225" ], "ideal_answer": [ "Histone H3K27ac separates active from poised enhancers and predicts developmental state . In contrast, elements of the second class 'poised enhancers' are linked to genes inactive in hESCs . They are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation .", "Enhancers cause a high level of transcription and activation of chromatin structure at target genes . Individual chromatin marks, such as H3K27ac, have been identified to distinguish active from inactive enhancers . In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H327ac and enrichment of histone H3 lysine 27 trimethylation .", "Conversion of inactive enhancers to an active state is marked by accumulation of H3K4me1 and H3K27ac histone marks.", "Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances . In contrast, elements of the second class 'poised enhancers' are distinguished by the absence of H3K27ac and enrichment of histone H3 lysine 27 trimethylation . They are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation and mesoderm formation .", "Monomethylation of histone H3 on Lys 27 (H3K27) is associated with active and inactive enhancers, respectively. An enhancer chromatin state signature associated withactive enhancers may be defined by high levels of H3 K27 acetylation, nucleosome displacement, hypersensitivity to sonication, and strong suppression of enhancer activity by DNase I.", "We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of MLL4 and p300. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an \"active enhancer landscape\" and defines a detailed mechanism for the joint deposition of H3K4me1 and H3K27ac." ], "exact_answer": [ "H3K27ac", "Histone 3 Lysine 27 acetylation" ], "type": "factoid", "id": "5fe30e06a43ad31278000037", "snippets": [ { "offsetInBeginSection": 226, "offsetInEndSection": 474, "text": "We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of MLL4 and p300. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28732206", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1167, "text": "This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an \"active enhancer landscape\" and defines a detailed mechanism for the joint deposition of H3K4me1 and H3K27ac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28732206", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 1168, "text": "In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21160473", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 412, "text": "Individual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 842, "text": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106759", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1121, "text": "rthermore, like H3K27ac, H3K9ac and H3K14ac can also differentiate active enhancers from inactive ones. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22920947", "endSection": "abstract" }, { "offsetInBeginSection": 1783, "offsetInEndSection": 1914, "text": " observation suggests that histone acetyl transferases (HATs) prime inactive genes by H3K14ac for stimuli dependent activation. In ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22920947", "endSection": "abstract" }, { "offsetInBeginSection": 971, "offsetInEndSection": 1167, "text": "e level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25984238", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 882, "text": "Moreover, repressed regions are trimethylated at lysines 9 and 27, suggesting that these histone modifications represent a mark for inactive PcG-controlled regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15448640", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 417, "text": "vidual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers. Howe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038352", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1589, "text": "he active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305225", "endSection": "abstract" } ] }, { "body": "What does DMARD stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30629813" ], "ideal_answer": [ "DMARD stands for disease-modifying antirheumatic drug." ], "exact_answer": [ "disease-modifying antirheumatic drug" ], "type": "factoid", "id": "602593101cb411341a0000ab", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Cost-Effectiveness of Combination Disease-Modifying Antirheumatic Drugs Versus Tumor Necrosis Factor Inhibitors in Active Rheumatoid Arthritis: A Pragmatic, Randomized, Multicenter Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30629813", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 370, "text": "To determine whether intensive combinations of conventional synthetic disease-modifying antirheumatic drugs (csDMARDS) achieve similar clinical benefits more cheaply than high-cost biologics such as tumor necrosis factor inhibitors (TNFi) in patients with active rheumatoid arthritis (RA) whose illness has failed to respond to methotrexate and another DMARD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30629813", "endSection": "abstract" } ] }, { "body": "Can SMAD6 variants cause craniosynostosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32499606" ], "ideal_answer": [ "Yes, SMAD6 variants can cause craniosynostosis.", "Yes. Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. Functional analysis is important to evaluate missense variants. Genotyping of rs1884302 is not clinically useful. Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure." ], "exact_answer": "yes", "type": "yesno", "id": "601c1a271cb411341a000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "SMAD6 variants in craniosynostosis: genotype and phenotype evaluation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32499606", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1526, "text": "Enrichment of heterozygous missense and truncating SMAD6 variants was previously reported in nonsyndromic sagittal and metopic synostosis, and interaction of SMAD6 variants with a common polymorphism nearBMP2 (rs1884302) was proposed to contribute to inconsistent penetrance. We determined the occurrence of SMAD6 variants in all types of craniosynostosis, evaluated the impact of different missense variants on SMAD6 function, and tested independently whether rs1884302 genotype significantly modifies the phenotype.METHODS: We performed resequencing of SMAD6 in 795 unsolved patients with any type of craniosynostosis and genotyped rs1884302 in SMAD6-positive individuals and relatives. We examined the inhibitory activity and stability of SMAD6 missense variants.RESULTS: We found 18 (2.3%) different rare damaging SMAD6 variants, with the highest prevalence in metopic synostosis (5.8%) and an 18.3-fold enrichment of loss-of-function variants comparedwith gnomAD data (P\u2009<\u200910-7). Combined with eight additional variants, \u226520/26 were transmitted from an unaffected parent but rs1884302 genotype did not predict phenotype.CONCLUSION: Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. Functional analysis is important to evaluate missense variants. Genotyping of rs1884302 is not clinically useful. Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32499606", "endSection": "abstract" } ] }, { "body": "What is targeted by Pexidartinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28536100", "http://www.ncbi.nlm.nih.gov/pubmed/31229240", "http://www.ncbi.nlm.nih.gov/pubmed/31258629", "http://www.ncbi.nlm.nih.gov/pubmed/32440095", "http://www.ncbi.nlm.nih.gov/pubmed/32297819", "http://www.ncbi.nlm.nih.gov/pubmed/31862477", "http://www.ncbi.nlm.nih.gov/pubmed/30825104", "http://www.ncbi.nlm.nih.gov/pubmed/31602563", "http://www.ncbi.nlm.nih.gov/pubmed/30926949", "http://www.ncbi.nlm.nih.gov/pubmed/32943455", "http://www.ncbi.nlm.nih.gov/pubmed/31213500", "http://www.ncbi.nlm.nih.gov/pubmed/31240240", "http://www.ncbi.nlm.nih.gov/pubmed/31848580", "http://www.ncbi.nlm.nih.gov/pubmed/32306101", "http://www.ncbi.nlm.nih.gov/pubmed/32617868", "http://www.ncbi.nlm.nih.gov/pubmed/30002809" ], "ideal_answer": [ "Pexidartinib is a selective tyrosine kinase inhibitor against CSF1R." ], "exact_answer": [ "CSF1R" ], "type": "factoid", "id": "5e44cf61f5547e6e27000001", "snippets": [ { "offsetInBeginSection": 368, "offsetInEndSection": 805, "text": "Elucidation of the importance of the colony-stimulating factor (CSF1)/CSF1 receptor (CSF1R) pathway in the pathogenesis of this disease has created significant interest in targeting this pathway as a novel TGCT treatment approach. Pexidartinib, a selective tyrosine kinase inhibitor against CSF1R, showed an 83% disease control rate (52% with partial response and 31% with stable disease) in a recent phase 1 study of patients with TGCT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30002809", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 709, "text": "We show that M-CSFR inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of TAMs, circulating nonclassical monocytes, as well as amount of neoangiogenesis and ascites in mesothelioma mouse models, but did not improve survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28536100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Pexidartinib (TURALIO\u2122) is an orally administered small molecule tyrosine kinase inhibitor with selective activity against the colony-stimulating factor 1 (CSF1) receptor, KIT proto-oncogene receptor tyrosine kinase (KIT) and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation (FLT3-ITD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31602563", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 1073, "text": "ODS: This was an investigator-initiated, phase I, dose escalation study of the MEK inhibitor binimetinib combined with pexidartinib, a potent inhibitor of CSF1R, KIT, and FLT3, in patients with advanced or metastatic GIST who progressed on imatinib. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31213500", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 324, "text": "Pexidartinib, an oral inhibitor of tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), KIT, and FLT3, is FDA approved in adults with tenosynovial giant cell tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943455", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 817, "text": "Pexidartinib is a CSF1R antagonist that is prescribed for the treatment of tenosynovial giant cell tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31862477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30825104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "PURPOSE: Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306101", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 323, "text": "tumors. Pexidartinib, an oral inhibitor of tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), KIT, and FLT3, is FDA approved in adults with tenosynovial giant cell tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Pexidartinib (TURALIO\u2122) is an orally administered small molecule tyrosine kinase inhibitor with selective activity against the colony-stimulating factor 1 (CSF1) receptor, KIT proto-oncogene receptor tyrosine kinase (KIT) and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation (FLT3-ITD). In August", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31602563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Pexidartinib (PLX3397) is a small molecule tyrosine kinase and colony-stimulating factor-1 inhibitor with FDA breakthrough therapy designation for tenosynovial giant-cell tumor, and currently under study in several other tumor types, including breast cancer, non-Hodgkin's lymphoma, and glioblastoma. Here, we", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31240240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30825104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Purpose: To evaluate the safety, recommended phase\u2009II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor\u20091 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31258629", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 153, "text": "Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306101", "endSection": "title" }, { "offsetInBeginSection": 704, "offsetInEndSection": 939, "text": "Pexidartinib is an oral tyrosine kinase inhibitor with selective inhibition of colony-stimulating factor 1 receptor and is the first systemic therapy to show significant improvement in overall response rates when compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32617868", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 599, "text": "tor 1 (CSF1). Pexidartinib (Turalio\u2122) is a selective CSF1\u00a0R inhibitor, which was recently approved by the FDA for the trea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32297819", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 793, "text": "t approach. Pexidartinib, a selective tyrosine kinase inhibitor against CSF1R, showed an 83% disease control rate (52% with partial response and 31% with stable disease) in a recent phase 1 study of patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30002809", "endSection": "abstract" }, { "offsetInBeginSection": 1301, "offsetInEndSection": 1419, "text": "Pexidartinib is an orally bioavailable and potent inhibitor of CSF-1R which is one of the most clinically used agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32440095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Pexidartinib, a Novel Small Molecule CSF-1R Inhibitor in Use for Tenosynovial Giant Cell Tumor: A Systematic Review of Pre-Clinical and Clinical Development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32440095", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 398, "text": "We aimed to evaluate pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT to provide them with a viable systemic treatment option, especially in cases that are not amenable to surgical resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31229240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The CSF1 receptor inhibitor pexidartinib (PLX3397) reduces tissue macrophage levels without affecting glucose homeostasis in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30926949", "endSection": "title" }, { "offsetInBeginSection": 100, "offsetInEndSection": 461, "text": "To address the role of these cells in disease pathogenesis, we depleted microglia from R6/2 mice, a rapidly progressing model of Huntington's disease marked by behavioural impairment, mutant huntingtin (mHTT) accumulation, and early death, through colony-stimulating factor 1 receptor inhibition (CSF1Ri) with pexidartinib (PLX3397) for the duration of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31848580", "endSection": "abstract" } ] }, { "body": "What is the microgenderome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26757840", "http://www.ncbi.nlm.nih.gov/pubmed/27808584", "http://www.ncbi.nlm.nih.gov/pubmed/24627581", "http://www.ncbi.nlm.nih.gov/pubmed/30298433" ], "ideal_answer": [ "The sexually dimorphic microbiome has been termed the 'microgenderome'." ], "exact_answer": [ "The sexually dimorphic microbiome has been termed the 'microgenderome'." ], "type": "factoid", "id": "5e920fe42d3121100d00000f", "snippets": [ { "offsetInBeginSection": 1119, "offsetInEndSection": 1244, "text": "A concept of \"microgenderome\" related to the potential role of sex hormone modulation of the gut microbiota is also emerging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24627581", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The 'microgenderome' provides a paradigm shift that highlights the role of sex differences in the host-microbiota interaction relevant for autoimmune and neuro-immune conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26757840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "The microgenderome defines the interaction between microbiota, sex hormones and the immune system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27808584", "endSection": "abstract" }, { "offsetInBeginSection": 964, "offsetInEndSection": 1036, "text": "The sexually dimorphic microbiome has been termed the 'microgenderome'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30298433", "endSection": "abstract" } ] }, { "body": "What causes yellowing of the skin and eyes, also known as jaundice, in patients with liver failure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27904243", "http://www.ncbi.nlm.nih.gov/pubmed/21498981", "http://www.ncbi.nlm.nih.gov/pubmed/8666325", "http://www.ncbi.nlm.nih.gov/pubmed/26015697", "http://www.ncbi.nlm.nih.gov/pubmed/29187150", "http://www.ncbi.nlm.nih.gov/pubmed/24834192", "http://www.ncbi.nlm.nih.gov/pubmed/30441460", "http://www.ncbi.nlm.nih.gov/pubmed/26052974", "http://www.ncbi.nlm.nih.gov/pubmed/14765767", "http://www.ncbi.nlm.nih.gov/pubmed/30266131" ], "ideal_answer": [ "Jaundice refers to yellow coloration of the skin and the sclera (white of the eyes) of newborn babies that result from the accumulation of bilirubin in the skin and mucous membranes." ], "type": "summary", "id": "5e67b8bb1af46fc13000001b", "snippets": [ { "offsetInBeginSection": 153, "offsetInEndSection": 394, "text": "n enzyme required to convert bilirubin into a more soluble form that can then be removed from the body. Absence or severe deficiency of this enzyme can lead to bilirubin accumulation in the body resulting in yellow skin and eyes (jaundice). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30266131", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 204, "text": " jaundice refers to yellow coloration of the skin and the sclera (whites of the eyes) of newborn babies that result from the accumulation of bilirubin in the skin and mucous membranes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26015697", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 879, "text": "however, are hindered by the relatively limited knowledge about the impact of different amounts of extravascular bilirubin on skin spectral responses and on the onset of jaundice, the resulting yellow-tinted skin appearance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30441460", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 173, "text": "Febrile jaundice results clinically in generalized yellow coloration of the teguments and mucous membranes due to excess plasma bilirubin, accompanied by fever. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29187150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Jaundice is a yellowish pigmentation of skin and mucous membranes caused by hyperbilirubinemia, which itself has various causes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498981", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 803, "text": " signs of jaundice occur when the serum bilirubin level exceeds 2.5 to 3 mg/dL. In all", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27904243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Jaundice is a clinical manifestation of disorders of underlying bilirubin metabolism, hepatocellular dysfunction, or biliary obstruction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27904243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Jaundice is a clinical manifestation of disorders of underlying bilirubin metabolism, hepatocellular dysfunction, or biliary obstruction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27904243", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 793, "text": "Clinical signs of jaundice occur when the serum bilirubin level exceeds 2.5 to 3 mg/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27904243", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 375, "text": "Prehepatic causes of jaundice include hemolysis and hematoma resorption, which lead to elevated levels of unconjugated (indirect) bilirubin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14765767", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1021, "text": "The most common causes of jaundice were drug-induced hepatitis, occurring in 11 patients (31 percent), and alcoholic liver disease, occurring in 5 (13 percent).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8666325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Jaundice is one of the notable markers of liver malfunction in our body, revealing a significant rise in the concentration of an endogenous yellow pigment bilirubin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26052974", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 796, "text": "Clinical signs of jaundice occur when the serum bilirubin level exceeds 2.5 to 3 mg/dL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27904243", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 452, "text": "This destruction has two consequences: leaking ALT and AST liver enzymes which increases during the course of disease and accumulation of bilirubin- a red pigmented compound released from dead red cells- which causes the yellow coloration of eyes and skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24834192", "endSection": "abstract" } ] }, { "body": "Is Tcf3 associated with the Wnt pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "http://www.ncbi.nlm.nih.gov/pubmed/31033094", "http://www.ncbi.nlm.nih.gov/pubmed/23063976", "http://www.ncbi.nlm.nih.gov/pubmed/20951344", "http://www.ncbi.nlm.nih.gov/pubmed/17018284", "http://www.ncbi.nlm.nih.gov/pubmed/23090119", "http://www.ncbi.nlm.nih.gov/pubmed/30631148", "http://www.ncbi.nlm.nih.gov/pubmed/22007134", "http://www.ncbi.nlm.nih.gov/pubmed/25832347", "http://www.ncbi.nlm.nih.gov/pubmed/23505158", "http://www.ncbi.nlm.nih.gov/pubmed/22270545", "http://www.ncbi.nlm.nih.gov/pubmed/22573616", "http://www.ncbi.nlm.nih.gov/pubmed/19074834", "http://www.ncbi.nlm.nih.gov/pubmed/18467660", "http://www.ncbi.nlm.nih.gov/pubmed/21285352", "http://www.ncbi.nlm.nih.gov/pubmed/11524435", "http://www.ncbi.nlm.nih.gov/pubmed/23492770", "http://www.ncbi.nlm.nih.gov/pubmed/24648413", "http://www.ncbi.nlm.nih.gov/pubmed/24832538", "http://www.ncbi.nlm.nih.gov/pubmed/25375219", "http://www.ncbi.nlm.nih.gov/pubmed/28346462", "http://www.ncbi.nlm.nih.gov/pubmed/23658527" ], "ideal_answer": [ "Tcf3 is a component of the Wnt/\u03b2-catenin and Notch signaling pathways.", "TCF3, a novel positive regulator of osteogenesis, plays a crucial role in modulating the diverse effect of canonical Wnt signaling. We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells.", "A terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3) co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog . Overexpression of TCF3 (transcription factor 3) attenuated the effect of miR-17 on modulating Wnt signaling .", "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It's a family of transcription factors that regulate the growth of cells.", "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It regulates the growth and differentiation of cells.", "Yes, Tcf3 is associated with the Wnt pathway.", "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog.", "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It's a family of transcription factors that regulate the growth and differentiation of cells.", "A terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog . The noncanonical Wnt signaling pathway, through actions of Tcf3, can antagonize the canonical pathway .", "Yes. Tcf3 is associated with the Wnt/\u03b2-catenin pathway.", "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It's a family of transcription factors that regulate the growth and differentiation of pluripotent cells.", "Yes, TCF3 is a key transcription factor of the canonical Wnt pathway.", "Yes, Tcf3 is involved in the activation of the Wnt pathway." ], "exact_answer": "yes", "type": "yesno", "id": "5fdb4124a43ad31278000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23492770", "endSection": "title" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1285, "text": "Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23492770", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 956, "text": "Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23063976", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1292, "text": "In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G(1) to S transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23063976", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 319, "text": "TCF3 (also known as TCF7L1) is a member of the TCF/LEF transcription factor family that is central in regulating epidermal and embryonic stem cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090119", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1156, "text": "We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells while repressing another distinct target subset. In the normal mouse mammary gland, Tcf3 is highly expressed in terminal end buds, structures that lead duct development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090119", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1227, "text": "Tcf3 is essential within the neural ectoderm to maintain anterior character and that its interaction with Hesx1 ensures the repression of Wnt targets in the developing forebrain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22007134", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 558, "text": "We report here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1104, "text": "Our results suggest that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The wnt pathway regulates the steady state level of beta-catenin, a transcriptional coactivator for the Tcf3/Lef1 family of DNA binding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11524435", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1385, "text": "Along with evidence that a significant amount of Tcf protein is nonnuclear, these findings suggest that CK1epsilon can modulate wnt signaling in vivo by regulating both the beta-catenin-Tcf3 and the GBP-dsh interfaces.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11524435", "endSection": "abstract" }, { "offsetInBeginSection": 879, "offsetInEndSection": 1035, "text": "RA increases the expression of ligands and receptors of the noncanonical Wnt pathway (Wnt 5a, 7a, Fzd2 and Fzd6), downstream signaling, and Tcf3 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24648413", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 758, "text": "The noncanonical Wnt signaling pathway, through actions of Tcf3, can antagonize the canonical pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24648413", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 557, "text": "We report here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 898, "text": "Both Tcf3 depletion and Wnt pathway activation cause increased expression of Oct4, Nanog, and other pluripotency factors and produce ES cells that are refractory to differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 757, "text": "Here, we show that injection of a hesx1 morpholino into a 'sensitised' zygotic headless (tcf3) mutant background leads to severe forebrain and eye defects, suggesting an interaction between Hesx1 and the Wnt pathway during zebrafish forebrain development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22007134", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1227, "text": "In addition, we reveal that Tcf3 is essential within the neural ectoderm to maintain anterior character and that its interaction with Hesx1 ensures the repression of Wnt targets in the developing forebrain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22007134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23492770", "endSection": "title" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1695, "text": "Our studies located the position of Wnts, downstream LEF1 and TCF3 and stem cell marker proteins, which provide new information in understanding the role of the Wnt singaling pathway in whisker follicles' growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25832347", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "The transcription factor T-cell factor 3 (TCF3), one component of the Wnt pathway, is known as a cell-intrinsic inhibitor of many pluripotency genes in embryonic stem cells (ESCs) that influences the balance between pluripotency and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31033094", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1379, "text": "Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23492770", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 989, "text": "We also find that TCF3 phosphorylation is triggered by canonical Wnt ligands, LRP6, and dominant negative mutants for Axin and GSK3, indicating that this process shares the same upstream regulators with \u03b2-catenin stabilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21285352", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1074, "text": "Wnt pathway stimulation also triggers \u03b2-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23505158", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 769, "text": "We show that menin physically interacts with proteins involved in the canonical Wnt signaling pathway, including beta-catenin, TCF3 (TCFL1), and weakly with TCF4 (TCFL2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074834", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 356, "text": "T-cell factor 3 (Tcf3) is a component of the Wnt signaling and a dominant downstream effector in ESCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467660", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 363, "text": " factor 3 (Tcf3) is a component of the Wnt signaling and a dominant downstream effector in ESCs. Despit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18467660", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 566, "text": "rt here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Thus, Tc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1099, "text": "Tcf3, is recruited to a palindromic motif enriched in the promoter of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which mediate the Wnt-dependent anti-proliferative effect in mESCs. Consistently, abl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346462", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 460, "text": "nonical Wnt/\u03b2-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. Howe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346462", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1364, "text": "g increases the dissociation of Tcf1 and the association of Tcf3 at promoters of genes that regulate stemness (e.g., NR5A2, Lrh-1) or differentiation (e.g. Cyr61, Zic5). Knockdown of Tcf3 increases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24648413", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1497, "text": "pport the existence of a regulatory circuit whereby Wnt/\u03b2-catenin counteracts Tcf3 repression of Lef1, which subsequently activates target gene expression via Lef1-\u03b2-catenin complexes. We propose that the Tcf/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22573616", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 1032, "text": " with a requirement for Wnt signalling repression, we highlight a synergistic gene dosage-dependent interaction between Hesx1 and Tcf3, a transcriptional repressor of Wnt target genes, to maintain anterior forebrain identity during mouse embryogenesis. In addition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22007134", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1056, "text": "expression of ligands and receptors of the noncanonical Wnt pathway (Wnt 5a, 7a, Fzd2 and Fzd6), downstream signaling, and Tcf3 expression. RA reduces the phosp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24648413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND AND OBJECTIVES: Transcription factor 3 (TCF3) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25375219", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 440, "text": "We demonstrate that mouse Tcf3 mediates repression of both moderate and high levels of canonical Wnt signaling, by either competing with other members of the Tcf/Lef family for binding to \u03b2-catenin, or for binding to DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22270545", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 313, "text": "TCF3 is a transcriptional repressor that has been implicated in Wnt signaling and plays key roles in embryonic axis specification and stem cell differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20951344", "endSection": "abstract" }, { "offsetInBeginSection": 1577, "offsetInEndSection": 1876, "text": "Our data show for the first time that Wnt signaling down-regulates Tcf3 expression, possibly at both the transcriptional and post-transcriptional levels, and thus highlight a novel mechanism through which Wnt signaling inhibits neuro-ectodermal lineage differentiation in mouse embryonic stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 896, "text": "We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24832538", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 898, "text": "We found that down-regulation of Tcf3, a member of the Tcf/Lef family and a key player in the control of self-renewal and pluripotency, represents a specific and primary response to Wnt activation in ESCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1100, "text": "Wnt16b also activated the RhoA/Rac1 signaling cascade suggesting the activation of a non-canonical Wnt pathway in TCF3-PBX1 cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30631148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with TCF3-PBX1 fusion gene expression has constitutively elevated levels of Wnt16b and ROR1 (receptor tyrosine kinase-like orphan receptor), a ligand and a receptor from the Wnt signaling pathway, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30631148", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1036, "text": "We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells while repressing another distinct target subset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23090119", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1640, "text": "Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24832538", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1287, "text": "We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling, in NPCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24832538", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1046, "text": "These data suggest that in the absence of Wnt signals, Tcf3 may function in skin SCs to maintain an undifferentiated state and, through Wnt signaling, directs these cells along the hair lineage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17018284", "endSection": "abstract" } ] }, { "body": "Have the rotavirus vaccines changed the predominant rotavirus genotypes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29790933" ], "ideal_answer": [ "The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains." ], "exact_answer": "yes", "type": "yesno", "id": "5e766256835f4e4777000003", "snippets": [ { "offsetInBeginSection": 166, "offsetInEndSection": 313, "text": "This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29790933", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1182, "text": "G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29790933", "endSection": "abstract" }, { "offsetInBeginSection": 1195, "offsetInEndSection": 1521, "text": "The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29790933", "endSection": "abstract" } ] }, { "body": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32453716", "http://www.ncbi.nlm.nih.gov/pubmed/29159890" ], "ideal_answer": [ "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome.", "Dysfunction of the ciliary ARMC9/TOGARAM1 protein causes Joubert syndrome.", "Joubert syndrome (JBTS) is a recessive neurodevelopmental disorder caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein.", "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. All known JBTS genes encode proteins involved in the structure or function of primary cilia, ubiquitous antenna-like organelles essential for cellular signal transduction.", "Joubert syndrome is a rare autosomal recessive disorder caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein.", "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. Joubert syndrome (JBTS) is a recessive neurodevelopmental ciliopathy characterized by a pathognomonic hindbrain malformation.", "Joubert syndrome (JBTS) is a rare autosomal recessive disorder caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein." ], "exact_answer": [ "Joubert syndrome" ], "type": "factoid", "id": "601d2d001cb411341a00002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32453716", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1386, "text": "Joubert syndrome (JBTS) is a recessive neurodevelopmental ciliopathy characterized by a pathognomonic hindbrain malformation. All known JBTS genes encode proteins involved in the structure or function of primary cilia, ubiquitous antenna-like organelles essential for cellular signal transduction. Here, we used the recently identified JBTS-associated protein armadillo repeat motif-containing 9 (ARMC9) in tandem-affinity purification and yeast 2-hybrid screens to identify a ciliary module whose dysfunction underlies JBTS. In addition to the known JBTS-associated proteins CEP104 and CSPP1, we identified coiled-coil domain containing 66 (CCDC66) and TOG array regulator of axonemal microtubules 1 (TOGARAM1) as ARMC9 interaction partners. We found that TOGARAM1 variants cause JBTS and disrupt TOGARAM1 interaction with ARMC9. Using a combination of protein interaction analyses, characterization of patient-derived fibroblasts, and analysis of CRISPR/Cas9-engineered zebrafish and hTERT-RPE1 cells, we demonstrated that dysfunction of ARMC9 or TOGARAM1 resulted in short cilia with decreased axonemal acetylation and polyglutamylation, but relatively intact transition zone function. Aberrant serum-induced ciliary resorption and cold-induced depolymerization in ARMC9 and TOGARAM1 patient cell lines suggest a role for this new JBTS-associated protein module in ciliary stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32453716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32453716", "endSection": "title" }, { "offsetInBeginSection": 799, "offsetInEndSection": 977, "text": "Our report of variant in ARMC9 Leading to Joubert syndrome phenotype (JS30), elucidates the genetic heterogeneity of Joubert syndrome, and expands the gene list for ciliopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29159890", "endSection": "abstract" } ] }, { "body": "Does head ct increase brain tumor risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21831864", "http://www.ncbi.nlm.nih.gov/pubmed/25052516", "http://www.ncbi.nlm.nih.gov/pubmed/19018153", "http://www.ncbi.nlm.nih.gov/pubmed/31235364", "http://www.ncbi.nlm.nih.gov/pubmed/24157736", "http://www.ncbi.nlm.nih.gov/pubmed/28809584", "http://www.ncbi.nlm.nih.gov/pubmed/26598533", "http://www.ncbi.nlm.nih.gov/pubmed/30020493", "http://www.ncbi.nlm.nih.gov/pubmed/24569470", "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "http://www.ncbi.nlm.nih.gov/pubmed/32759481", "http://www.ncbi.nlm.nih.gov/pubmed/19551621" ], "ideal_answer": [ "Yes, there appears to be a small but higher than expected lifetime risk of secondary brain tumors in persons who underwent CT scans during childhood." ], "exact_answer": "yes", "type": "yesno", "id": "5e323e93fbd6abf43b000059", "snippets": [ { "offsetInBeginSection": 749, "offsetInEndSection": 1198, "text": "Excess relative risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs. Tumor incidence increased with number of pediatric head CTs in a dose-dependent manner, with measurable excess incidence even after a single scan. Converging evidence from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 591, "text": "Recent epidemiologic evidence from a national registry of children who underwent CT scans suggests a higher-than-expected incidence of secondary tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157736", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1810, "text": "However, we found 1) a statistically significant correlation between radiation dose and age at procedure, as well as number and type of procedures, and 2) a substantial increase in lifetime predicted risk of tumor above baseline in the cohort of young children who undergo neurointerventions.CONCLUSIONS: Although neurointerventional procedures have dramatically improved the prognosis of children facing serious cerebrovascular conditions, the predicted risk of secondary tumors, particularly in the youngest patients and those undergoing multiple procedures, is sobering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24157736", "endSection": "abstract" }, { "offsetInBeginSection": 1346, "offsetInEndSection": 1576, "text": "Conclusion When prevalent cases of meningioma at first exposure to CT of the head are excluded, no statistically significant increase in risk of meningioma was found among exposed subjects compared with unexposed control subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28809584", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1494, "text": " data suggest that 1 excess brain malignancy occurred after 4000 brain CTs (40 mSv per scan) and that the estimated risk in the 10 years following CT exposure was 1 brain tumor per 10,000 patients exposed to a 10 mGy scan at less than 10 years of age.CONCLU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25052516", "endSection": "abstract" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1389, "text": "SIONS: The model predicts that the effective radiation dose from a single head CT is capable of inducing a thyroid or brain tumor in an infant or child. These", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19018153", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1418, "text": "Neither whole head CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32759481", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1165, "text": "rison of exposed and unexposed cohorts showed that there was no statistically significant increase in the risk of meningioma after exposure to CT of the head (HR: 1.49; 95% confidence interval: 0.97, 2.30; P = .07). If incident c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28809584", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1216, "text": "from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients. However, refined e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 911, "text": "ve risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs. Tumor incidence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "endSection": "abstract" }, { "offsetInBeginSection": 1322, "offsetInEndSection": 1435, "text": " CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours. Although this st", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32759481", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1114, "text": "o for developing a brain tumour from having a brain CT was 0.93 (95% confidence interval: 0.38-1.82). This was har", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32759481", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1042, "text": "Tumor incidence increased with number of pediatric head CTs in a dose-dependent manner, with measurable excess incidence even after a single scan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1197, "text": "Converging evidence from epidemiological studies supported a small excess risk of brain tumor incidence after even a single CT exam in pediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "endSection": "abstract" }, { "offsetInBeginSection": 749, "offsetInEndSection": 895, "text": "Excess relative risk of new brain tumor averaged 1.29 (95% confidence interval, 0.66-1.93) for pediatric patients exposed to one or more head CTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 748, "text": "Epidemiological studies consistently cited increased tumor incidence in pediatric patients (ages 0-18) exposed to head CTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29717567", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 1295, "text": "RESULTS: A positive correlation between exposure to CT scans and developing central nervous system tumors was evident in all cohorts. The strength of the association varied across the studies. Exclusion of patients with predisposing factors to central nervous system tumors was examined in four studies with a decreased risk to develop central nervous system tumors noted in three studies. Two studies reported nonsignificant reduction in the excess relative risk per milliGray of brain dose after adjusting for predisposing factors, whereas the reduction was significant in one study. The frequency of CT exposure was proportional to the risk of developing tumors in two studies although not significantly maintained in two other studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31235364", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 1224, "text": "RESULTS: The overall risk was not significantly different in the two cohorts (incidence rate=36.72 per 100\u2009000 person-years in the exposed cohort, 28.48 per 100\u2009000 person-years in the unexposed cohort, hazard ratio (HR)=1.29, 95% confidence interval (CI)=0.90-1.85). The risk of benign brain tumour was significantly higher in the exposed cohort than in the unexposed cohort (HR=2.97, 95% CI=1.49-5.93). The frequency of CT examination showed strong correlation with the subsequent overall risk of malignancy and benign brain tumour.CONCLUSIONS: We found that paediatric head CT examination was associated with an increased incidence of benign brain tumour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24569470", "endSection": "abstract" }, { "offsetInBeginSection": 1463, "offsetInEndSection": 1557, "text": "CONCLUSIONS: We found evidence that CT-related radiation exposure increases brain tumor risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30020493", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1765, "text": "Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30020493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND: Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598533", "endSection": "abstract" }, { "offsetInBeginSection": 1497, "offsetInEndSection": 1643, "text": "IMPACT: Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26598533", "endSection": "abstract" }, { "offsetInBeginSection": 1045, "offsetInEndSection": 1339, "text": "The radiation-induced occurrence of meningiomas and other brain tumours most probably contributes to the continuously increasing incidence of these diseases which is observed in several industrial nations, as well as the exposure of the bone marrow by CT to the increase of childhood leukaemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21831864", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 905, "text": "1,000 annual paediatric CT investigations of the skull will lead to about 3 excess neoplasms in the head region, i.e., the probability of an induced late effect must be suspected in the range of some thousandths. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19551621", "endSection": "abstract" } ] }, { "body": "Which main viral protein is targeted by the drug remdesivir?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29511076", "http://www.ncbi.nlm.nih.gov/pubmed/30275474" ], "ideal_answer": [ "Viral Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease." ], "exact_answer": [ "Viral Polymerase" ], "type": "factoid", "id": "5e920be42d3121100d00000c", "snippets": [ { "offsetInBeginSection": 1404, "offsetInEndSection": 1758, "text": "Combined, the results indicate that GS-5734 interferes with the nsp12 polymerase even in the setting of intact ExoN proofreading activity and that resistance can be overcome with increased, nontoxic concentrations of GS-5734, further supporting the development of GS-5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29511076", "endSection": "title" }, { "offsetInBeginSection": 111, "offsetInEndSection": 282, "text": "In non-human primates, early initiation of polymerase inhibitors favipiravir and remdesivir improves survival, but whether they could be effective in patients is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30275474", "endSection": "abstract" } ] }, { "body": "What can be isolated from Pleurotus mutilus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28407921", "http://www.ncbi.nlm.nih.gov/pubmed/32041931", "http://www.ncbi.nlm.nih.gov/pubmed/27742734" ], "ideal_answer": [ "Pleuromutilins are antibiotics, isolated from the fungus, Pleurotus mutilus, that selectively inhibit bacterial translation and are semisynthetic derivatives of the naturally occurring tricyclic diterpenoid pleuromutilins." ], "type": "summary", "id": "5e6d1c271af46fc130000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Pleuromutilins are antibiotics that selectively inhibit bacterial translation and are semisynthetic derivatives of the naturally occurring tricyclic diterpenoid pleuromutilin, which received its name from the pleuromutilin-producing fungus Pleurotus mutilu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27742734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Enhanced production of pleuromutilin by Pleurotus mutilus and study on its molecular structure", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407921", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "This study aims to enhance the accumulation of pleuromutilin by Pleurotus mutilus and to analyze the molecular structure of pleuromutilin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Enhanced production of pleuromutilin by Pleurotus mutilus and study on its molecular structure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407921", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Pleuromutilins are antibiotics that selectively inhibit bacterial translation and are semisynthetic derivatives of the naturally occurring tricyclic diterpenoid pleuromutilin, which received its name from the pleuromutilin-producing fungus Pleurotus mutilus Tiamulin and valnemulin are two established derivatives in veterinary medicine for oral and intramuscular administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27742734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "BACKGROUND Pleuromutilin is a natural tricyclic, derived from the fungus, Pleurotus mutilus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32041931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "BACKGROUND Pleuromutilin is a natural tricyclic, derived from the fungus, Pleurotus mutilus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32041931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "This study aims to enhance the accumulation of pleuromutilin by Pleurotus mutilus and to analyze the molecular structure of pleuromutilin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28407921", "endSection": "abstract" } ] }, { "body": "Which type of pluripotency is Otx2 associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23154415", "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "http://www.ncbi.nlm.nih.gov/pubmed/27019633", "http://www.ncbi.nlm.nih.gov/pubmed/23719282", "http://www.ncbi.nlm.nih.gov/pubmed/30349051", "http://www.ncbi.nlm.nih.gov/pubmed/27732856", "http://www.ncbi.nlm.nih.gov/pubmed/32367046", "http://www.ncbi.nlm.nih.gov/pubmed/30413530", "http://www.ncbi.nlm.nih.gov/pubmed/23954875", "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "http://www.ncbi.nlm.nih.gov/pubmed/24905168", "http://www.ncbi.nlm.nih.gov/pubmed/27392793", "http://www.ncbi.nlm.nih.gov/pubmed/24931607", "http://www.ncbi.nlm.nih.gov/pubmed/27292645", "http://www.ncbi.nlm.nih.gov/pubmed/24338594", "http://www.ncbi.nlm.nih.gov/pubmed/30567463", "http://www.ncbi.nlm.nih.gov/pubmed/27920151", "http://www.ncbi.nlm.nih.gov/pubmed/21062744" ], "ideal_answer": [ "transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency. Otx2 and Oct4 drive early activation during embryonic stem cell transition from naive pluripotency.", "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the mesendoderm-to-neural fate switch by suppressing BMP4 and FGf2.", "The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells. Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition.", "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the Mesendoderm to Neuron fate switch.", "The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells.", "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the mesendoderm-to-neural fate switch by suppressing BMP4 and FGf2. The transcription factor OTX2 acts as a negative switch in the regulation of transition from naive to primed pluripotency.", "Otx2 is required to maintain the ESC metastable state by antagonizing ground state pluripotency and promoting commitment to differentiation. Furthermore, Otx2 is required for ESC transition into EpiSCs and, subsequently, to stabilize the EpiSC state by suppressing, in pluripotent cells, the mesendoderm-to-neural fate switch in cooperation with BMP4 and Fgf2. Otx2 is a novel intrinsic determinant controlling the functional integrity of ESCs and EpiSCs. Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency.", "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the mesendoderm-to-neural fate switch." ], "exact_answer": [ "formative pluripotency" ], "type": "factoid", "id": "5fd0d880a43ad31278000002", "snippets": [ { "offsetInBeginSection": 942, "offsetInEndSection": 1154, "text": "Specifically, the induction of the gastrulation markers T brachyury, Goosecoid, and Dkk1 and the neuroectodermal markers Otx2 and Hand1 was inhibited by Sall1 overexpression during embryoid body differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1359, "text": "These observations indicate that OTX2 and NANOG can form a negative feedback circuitry to regulate the pluripotency of porcine iPS cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 952, "text": "J\u03b4 retained the pluripotency gene-inducing ability of S\u03b4 when used alone and in combination with S\u03b4; a notable increase in the pluripotency gene expression was observed. Interestingly, J\u03b4 significantly induced the expression of HDAC8-controlled Otx2 and Lhx1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23719282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154415", "endSection": "title" }, { "offsetInBeginSection": 821, "offsetInEndSection": 1181, "text": "Otx2 is required to maintain the ESC metastable state by antagonizing ground state pluripotency and promoting commitment to differentiation. Furthermore, Otx2 is required for ESC transition into EpiSCs and, subsequently, to stabilize the EpiSC state by suppressing, in pluripotent cells, the mesendoderm-to-neural fate switch in cooperation with BMP4 and Fgf2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154415", "endSection": "abstract" }, { "offsetInBeginSection": 1405, "offsetInEndSection": 1515, "text": "We propose that Otx2 is a novel intrinsic determinant controlling the functional integrity of ESCs and EpiSCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154415", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1373, "text": "Pig iPSCs, which lacked expression of specific na\u00efve state markers KLF2/4/5 and TBX3, but expressed the primed state markers of Otx2 and Fabp7, share defining features with human ESCs and mouse EpiSCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24338594", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 1016, "text": "Here we show that OTX2 is highly expressed at the onset of rosette formation, when rosettes comprise no more than 3-5 cells, and that its expression precedes that of established markers of early neuronal differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954875", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931607", "endSection": "title" }, { "offsetInBeginSection": 365, "offsetInEndSection": 562, "text": "Here, we examined the role of Otx2 in this process in mouse ESCs and demonstrate that it plays a leading role in remodeling the gene regulatory networks as cells exit from ground state pluripotency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931607", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 667, "text": "Otx2 drives enhancer activation through affecting chromatin marks and the activity of associated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931607", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 989, "text": "Therefore, the Oct4-Otx2 regulatory axis actively establishes a new regulatory chromatin landscape during the early events that accompany exit from ground state pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931607", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 886, "text": "To unravel the Otx2 transcriptional network, we targeted the strongest Otx2-binding site in the Nanog promoter, finding that this site modulates the size of specific ESC-subtype compartments in cultured cells and promotes Nanog expression in\u00a0vivo, predisposing ICM differentiation to epiblast.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292645", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 847, "text": "Overexpression of OCT4 and SOX2 directly stimulated the expression of OTX2, RX1 and SIX3 in HDFs and iPSCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27019633", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 315, "text": "A\u00a0key factor in this process is Otx2, which is upregulated during the early stages of this transition and ultimately recruits Oct4 to a different set of enhancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732856", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 992, "text": "Induction of Otx2 causes the reorganization of acetylated Oct4 and results in the induction of the primed pluripotency gene network. Regulation of Oct4 by SirT1 may link stem cell development to environmental conditions, and it may provide strategies to manipulate epiblast cell state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27732856", "endSection": "abstract" }, { "offsetInBeginSection": 591, "offsetInEndSection": 815, "text": "In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30349051", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1204, "text": " Unexpectedly, OTX2 is also associated with primitive endoderm specification in human and non-human primate blastocysts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413530", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 559, "text": " We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27920151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Functional Antagonism between OTX2 and NANOG Specifies a Spectrum of\u00a0Heterogeneous Identities in Embryonic Stem Cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "title" }, { "offsetInBeginSection": 519, "offsetInEndSection": 670, "text": "Otx2-null ESCs possess naive identity features in LIF\u00a0+ FBS similar to Nanog-overexpressing ESCs and convert poorly into FGF-induced early primed state", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "abstract" }, { "offsetInBeginSection": 672, "offsetInEndSection": 813, "text": "When both Nanog and Otx2 are inactivated, ESCs cultured in LIF\u00a0+ FBS exhibit primed identity and weakened ability to convert into naive state", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1037, "text": "through mutual antagonism, NANOG and OTX2 specify the heterogeneous identity of ESCs cultured in LIF\u00a0+ FBS and individually predispose them for optimal response to naive or primed inducing factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 563, "text": "Here, we examined the role of Otx2 in this process in mouse ESCs and demonstrate that it plays a leading role in remodeling the gene regulatory networks as cells exit from ground state pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931607", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1162, "text": "Our results illuminate regulatory mechanisms underlying pluripotency and suggest that the capacity of transcription factors such as Otx2 and Oct4 to pioneer new enhancer sites is highly context dependent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905168", "endSection": "abstract" }, { "offsetInBeginSection": 1362, "offsetInEndSection": 1713, "text": "Taken together, our results establish readily efficient and safe protocols to produce iPSCs and iPSC-derived RPE cells, and underline that the reactivation of anterior neural transcription factor OTX2, eye field transcription factor RX1 and SIX3 in iPSCs is a feature of pluripotency acquisition and predetermines the potential of RPE differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27019633", "endSection": "abstract" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1336, "text": "In summary, this study demonstrates that there is a regulatory network mediated by miR-1343, in which downregulation of OTX2 by miR-1343 can elevate the expression of pluripotent genes that were then sustain the pluripotency of piPSCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30567463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Molecular network of miR-1343 regulates the pluripotency of porcine pluripotent stem cells via repressing OTX2 expression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30567463", "endSection": "title" }, { "offsetInBeginSection": 541, "offsetInEndSection": 800, "text": "Even when differentiation cues are blocked, premature Otx2 overexpression is sufficient to exit the naive state, induce transcription of a substantial subset of primed pluripotency-associated genes, and redirect Oct4 to previously inaccessible enhancer sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24905168", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 961, "text": "Otx2 is required to maintain the ESC metastable state by antagonizing ground state pluripotency and promoting commitment to differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154415", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1139, "text": "Importantly, the rise of OTX2 expression in these cells coincides with the down-regulation of the pluripotency marker OCT4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23954875", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1188, "text": "cESCs propagated in 2iL exhibited significant induction of genes associated with the na\u00efve pluripotent state (eg, REX1, TBX3) and downregulation of primed pluripotency markers (eg, OTX2, FGF5) (P\u2009<\u20090.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27392793", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "endSection": "abstract" }, { "offsetInBeginSection": 1002, "offsetInEndSection": 1213, "text": "n 2iL exhibited significant induction of genes associated with the na\u00efve pluripotent state (eg, REX1, TBX3) and downregulation of primed pluripotency markers (eg, OTX2, FGF5) (P\u2009<\u20090.05). Differential phosphoryla", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27392793", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 413, "text": "h core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency. Here we ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292645", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 829, "text": "07 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30349051", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 571, "text": "present study, we show that Sall1 is expressed in a differentiation-dependent manner and physically interacts with Nanog and Sox2, two components of the core pluripotency network. Genome-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062744", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 404, "text": "Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292645", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 583, "text": "Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32367046", "endSection": "abstract" } ] }, { "body": "Can AGY be used as antidiuretic replacement therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28035551" ], "ideal_answer": [ "No, AGY is an oral egg yolk anti-gliadin antibody used to neutralize gluten. It is used in patients with celiac disease." ], "exact_answer": "no", "type": "yesno", "id": "5e764732c6a8763d23000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "AGY, a Novel Egg Yolk-Derived Anti-gliadin Antibody, Is Safe for Patients with Celiac Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035551", "endSection": "title" }, { "offsetInBeginSection": 253, "offsetInEndSection": 377, "text": "Oral egg yolk anti-gliadin antibody (AGY) is a novel treatment to neutralize gluten and may improve the efficacy of the GFD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035551", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 472, "text": "To determine the safety, tolerability, and potential efficacy of AGY in patients with CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035551", "endSection": "abstract" }, { "offsetInBeginSection": 1234, "offsetInEndSection": 1431, "text": "Most patients had fewer celiac symptoms (especially tiredness, headache, and bloating), improved quality of life, lowered antibodies, and lowered LMER when taking AGY compared to the run-in period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035551", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1562, "text": "In our cohort, AGY was safe and potentially associated with improved CD-related outcome measures in patients on a GFD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28035551", "endSection": "abstract" } ] }, { "body": "What is caused by de novo sox6 variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32442410" ], "ideal_answer": [ "SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. De novo variants of the SOX6 gene have been identified in a large family with a complex phenotype variably associating attention-deficit/hyperactivity disorder (ADHD) with craniosynostosis, hearing impairment, developmental delay and carpal and tarsal fusions.", "De novo SOX6 variants cause a neurodevelopmental syndrome associated with ADHD, Craniosynostosis, and Osteochondromas." ], "type": "summary", "id": "601d2ec01cb411341a00002d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32442410", "endSection": "title" }, { "offsetInBeginSection": 193, "offsetInEndSection": 1736, "text": "For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes have been shown to cause severe developmental and adult syndromes, referred to as SOXopathies. We here provide evidence that SOX6 variants also cause a SOXopathy. Using clinical and genetic data, we identify 19 individuals harboring various types of SOX6 alterations and exhibiting developmental delay and/or intellectual disability; the individuals are from 17 unrelated families. Additional, inconstant features include attention-deficit/hyperactivity disorder (ADHD), autism, mild facial dysmorphism, craniosynostosis, and multiple osteochondromas. All variants are heterozygous. Fourteen are de novo, one is inherited from a mosaic father, and four offspring from two families have a paternally inherited variant. Intragenic microdeletions, balanced structural rearrangements, frameshifts, and nonsense variants are predicted to inactivate the SOX6 variant allele. Four missense variants occur in residues and protein regions highly conserved evolutionarily. These variants are not detected in the gnomAD control cohort, and the amino acid substitutions are predicted to be damaging. Two of these variants are located in the HMG domain and abolish SOX6 transcriptional activity in\u00a0vitro. No clear genotype-phenotype correlations are found. Taken together, these findings concur that SOX6 haploinsufficiency leads to a neurodevelopmental SOXopathy that often includes ADHD and abnormal skeletal and other features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32442410", "endSection": "abstract" } ] }, { "body": "Can secondary glioblastoma be caused by brain irradiation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2028149", "http://www.ncbi.nlm.nih.gov/pubmed/10845210", "http://www.ncbi.nlm.nih.gov/pubmed/29526937", "http://www.ncbi.nlm.nih.gov/pubmed/31088835", "http://www.ncbi.nlm.nih.gov/pubmed/12853693", "http://www.ncbi.nlm.nih.gov/pubmed/17583602", "http://www.ncbi.nlm.nih.gov/pubmed/23227384", "http://www.ncbi.nlm.nih.gov/pubmed/14714135", "http://www.ncbi.nlm.nih.gov/pubmed/32938807", "http://www.ncbi.nlm.nih.gov/pubmed/29713762", "http://www.ncbi.nlm.nih.gov/pubmed/15685439", "http://www.ncbi.nlm.nih.gov/pubmed/22102955", "http://www.ncbi.nlm.nih.gov/pubmed/18373067", "http://www.ncbi.nlm.nih.gov/pubmed/32649812", "http://www.ncbi.nlm.nih.gov/pubmed/23571774", "http://www.ncbi.nlm.nih.gov/pubmed/9810442", "http://www.ncbi.nlm.nih.gov/pubmed/17786001" ], "ideal_answer": [ "Yes, brain irradiation can cause secondary glioblastoma." ], "exact_answer": "yes", "type": "yesno", "id": "5e323d79fbd6abf43b000058", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29713762", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "[Radiation induced glioblastoma: a case report].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10845210", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10845210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17786001", "endSection": "title" }, { "offsetInBeginSection": 112, "offsetInEndSection": 236, "text": "The occurrence of glioblastoma multiforme following radiation and chemotherapy in acute lymphocytic leukaemia (ALL) is rare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17786001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia. R", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17786001", "endSection": "title" }, { "offsetInBeginSection": 381, "offsetInEndSection": 485, "text": "exact cause for the development of glioblastoma multiforme following therapy for ALL is not clear. A gen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17786001", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 507, "text": "ndary malignant and benign brain tumors such as astrocytoma, meningioma and glioblastoma have been described in long-term survivors of conventional myeloablative alloBMT. Here w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12853693", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1349, "text": "The authors consider irradiation-induced glioblastomas secondary to primarily verified medulloblastomas in patients who had previously undergone craniospinal irradiation as a component of combined treatment after tumor resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32649812", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1733, "text": "The authors analyzed patterns of occurrence of irradiation-induced glioblastomas depending on the molecular genetic group and clinical characteristics of patients after primary surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32649812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Secondary brain tumors rarely arise after cranial irradiation; among them, meningiomas and glioblastomas are the most common and secondary oligodendroglial tumors the most rare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18373067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Secondary glioblastoma multiforme (sGBM) can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23227384", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 415, "text": "Irradiation, however, acts as an oncogenic factor as a delayed effect and it is rare that glioblastoma multiforme develops during the remission period of ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "A cerebellar glioblastoma was discovered in a 28 year old woman, 5 years after a focal 50 grays brain irradiation for meningioma of the clivus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2028149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia. Report of 3 cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17786001", "endSection": "title" }, { "offsetInBeginSection": 805, "offsetInEndSection": 932, "text": "Secondary tumors including glioblastomas are under special attention since their occurrence is associated with a fatal outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32649812", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 492, "text": "We describe a case of radiation-induced glioblastoma after radiotherapy for germinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32938807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "[A Case of Radiation-induced Glioblastoma 29 Years after Treatments for Germinoma].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32938807", "endSection": "title" }, { "offsetInBeginSection": 156, "offsetInEndSection": 342, "text": "Paradoxically, radiation is also a risk factor for GBM development, raising the possibility that radiotherapy of brain tumors could promote tumor recurrence or trigger secondary gliomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31088835", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 913, "text": "An SMN may have a benign course, as in meningioma, or be a dilemma for the patient, as in glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14714135", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1510, "text": "During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9810442", "endSection": "abstract" }, { "offsetInBeginSection": 1326, "offsetInEndSection": 1643, "text": "In particular, children treated with X-irradiation for acute lymphoblastic leukemia show a significantly elevated risk of developing gliomas and primitive neuroectodermal tumor (PNET), often within 10 years after therapy. TP53 mutations are frequent in low-grade gliomas and secondary glioblastomas derived therefrom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15685439", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 920, "text": "Pathologic diagnoses were one glioblastoma, two cases of anaplastic astrocytoma, one medulloblastoma, one low-grade glioma, one high-grade glial tumor, and one atypical meningioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23571774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "A 22 year-old-man with acute lymphoblastic leukaemia had received prophylactic cranial irradiation and intrathecal chemotherapy. Eighteen years later a cerebellar glioblastoma multiforme was diagnosed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17583602", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 478, "text": "She developed glioblastoma 5.7 years after the initial GK surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29526937", "endSection": "abstract" } ] }, { "body": "Is aggrephagy a variant of autophagy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28837386", "http://www.ncbi.nlm.nih.gov/pubmed/29686608", "http://www.ncbi.nlm.nih.gov/pubmed/30027903" ], "ideal_answer": [ "Yes,\nthe selective branch of autophagy that deals with identification, capture and degradation of protein aggregates is called aggrephagy." ], "exact_answer": "yes", "type": "yesno", "id": "5e94902f2d3121100d000012", "snippets": [ { "offsetInBeginSection": 894, "offsetInEndSection": 1027, "text": "The selective branch of autophagy that deals with identification, capture and degradation of protein aggregates is called aggrephagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30027903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29686608", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 362, "text": ", it is largely unknown how misfolded polypeptides form aggresomes and are eventually cleared by the aggresome-macroautophagy/autophagy pathway, so-called aggrephagy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28837386", "endSection": "abstract" } ] }, { "body": "List the blood group antigens, associated with blood type", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27639389", "http://www.ncbi.nlm.nih.gov/pubmed/3560450", "http://www.ncbi.nlm.nih.gov/pubmed/29958715", "http://www.ncbi.nlm.nih.gov/pubmed/3227315", "http://www.ncbi.nlm.nih.gov/pubmed/28031957", "http://www.ncbi.nlm.nih.gov/pubmed/8735716", "http://www.ncbi.nlm.nih.gov/pubmed/29088730", "http://www.ncbi.nlm.nih.gov/pubmed/27755584", "http://www.ncbi.nlm.nih.gov/pubmed/29981282", "http://www.ncbi.nlm.nih.gov/pubmed/32802553", "http://www.ncbi.nlm.nih.gov/pubmed/29499994", "http://www.ncbi.nlm.nih.gov/pubmed/4030394", "http://www.ncbi.nlm.nih.gov/pubmed/1355324", "http://www.ncbi.nlm.nih.gov/pubmed/7679772", "http://www.ncbi.nlm.nih.gov/pubmed/3166398", "http://www.ncbi.nlm.nih.gov/pubmed/28938239", "http://www.ncbi.nlm.nih.gov/pubmed/30324575", "http://www.ncbi.nlm.nih.gov/pubmed/27599872", "http://www.ncbi.nlm.nih.gov/pubmed/28297729" ], "ideal_answer": [ "ABO antigens are highly abundant in many human cell types, including platelets, vascular endotheliums, and red blood cells.", "The blood group antigens, associated with blood type, are: ab, von willebrand factor, o, a, de ritis, rhesus, b, factor viii, rresus d, platelets and abo.", "ABO antigens are highly abundant in many human cell types, including platelets, vascular endothelium, and red blood cells.", "The blood group antigens, associated with blood type, are: ab, von willebrand factor, o, a, de ritis, rhesus, b, factor vii, platelets." ], "exact_answer": [ [ "A" ], [ "B" ], [ "O" ], [ "Rh", "h", "RHd", "D" ] ], "type": "list", "id": "5e5e4fdb1af46fc130000009", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 133, "text": "ABO antigens are highly abundant in many human cell types, including platelets, vascular endothelium, and red blood cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28938239", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 270, "text": "We have previously developed waveguide-mode (WM) sensors for forward ABO and Rh(D) blood typing ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29499994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Blood group systems based on red blood cell antigens are genetically determined and can identify patients at risk. Type non-O of the ABO blood group system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29958715", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 478, "text": "We evaluated the ABO and Rhesus D antigen (RhD) blood types in a large cohort of chronic HF patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29958715", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 135, "text": "The aim of this study was to investigate the association between A, B, O, Rhesus (Rh)-positive and Rh-negative blood groups ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29981282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Evaluation of ABO blood groups and blood-based biomarkers as a predictor of growth kinetics of renal angiomyolipoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30324575", "endSection": "title" }, { "offsetInBeginSection": 49, "offsetInEndSection": 110, "text": "the impact of the ABO blood groups and blood-based biomarkers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30324575", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 56, "text": "Role of ABO Blood Type in Thrombosis Scoring Systems", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28297729", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "ABO blood group antigens have been reported to be associated with inflammation and infections which have been largely implicated in the onset and progression of immune-mediated diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088730", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 294, "text": "Type A and type B antigens are Neu5Gc and Neu5Ac, respectively, and the enzyme CMAH participating in the synthesis of Neu5Gc from Neu5Ac is associated with this cat blood group system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27755584", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 986, "text": "Specifically, we characterized and statistically evaluated the expression of histo-blood group (A, B, O) antigens on N-and O-linked glycans from BEC membrane proteins of various individuals that represented different blood group type and secretor status using a porous graphitic carbon liquid chromatography electrospray ionization mass spectrometry (PGC-LC-ESI-MS) based glycomics approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27639389", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 519, "text": "In the present study a panel of MoABs against different type 1 chain derived blood group antigens, comprising A, B, H type 1, Le(a), sialyl-Le(a) (CA 19-9), sialyl type 1 structure (CA 50), and Le(b) was used to investigate their immunoreactivity in 38 medullary carcinomas of the thyroid (MTC) and in normal thyroid tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1355324", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1158, "text": "Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27599872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "ABO blood type is associated with renal outcomes in patients with IgA nephropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29088730", "endSection": "title" }, { "offsetInBeginSection": 391, "offsetInEndSection": 575, "text": "staining for alpha-N-acetylgalactosamine and alpha-galactose, the terminal sugars in blood group A and B antigens respectively, corresponded to a large extent with ABO blood type. One ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4030394", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 564, "text": "e, we describe the history and possible functions of the histoblood ABO group and then provide evidence for a role of blood group antigens in the most common cancer types worldwide using both blood type and SNP data. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28031957", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 794, "text": "contrary to the situation in the fetal and adult hamster pancreas, the induced pancreatic lesion expresses antigens with human blood group type specificities, including A, B, H, Leb, Lex, and Ley, antigens that are expressed, however, by fetal and adult duodenal epithelium. Considering the ori", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3227315", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 998, "text": "ically, we characterized and statistically evaluated the expression of histo-blood group (A, B, O) antigens on N-and O-linked glycans from BEC membrane proteins of various individuals that represented different blood group type and secretor status using a porous graphitic carbon liquid chromatography electrospray ionization mass spectrometry (PGC-LC-ESI-MS) based glycomics approach. From these ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27639389", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 270, "text": "us erosions. ABO secretor refers to those who secrete ABO blood group antigens based on their blood type in body fluids such as saliva, sweat, tears, semen, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32802553", "endSection": "abstract" }, { "offsetInBeginSection": 1126, "offsetInEndSection": 1338, "text": "of endothelial cells for blood group A and B antigens was confined to subjects of blood type A and B respectively, although three of nine type A specimens showed no lectin reactivity for group A antigen. Endothel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4030394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Human blood group polymorphisms are known to be determined by the expression of A, B or H antigens and the Lewis antigens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27639389", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 451, "text": "Protection against microbial infections has been associated with inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions and epithelial tissue surfaces, subsequently resulting in the presentation of different glycosylated terminal antigens on the cell surface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27639389", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 451, "text": "The expression of blood group-related antigens (A, B, H, Lewis(a), Lewis(b), Lewis(x), Lewis(y), carbohydrate antigen 19-9 and carcinoembryonic antigen) was investigated immunohistochemically in 75 cases of cholangiocarcinoma (31 peripheral type and 44 hilar type).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8735716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Expression of blood group-related antigens ABH, Lewis A, Lewis B, Lewis X, Lewis Y, and CA 19-9 in pancreatic cancer cells in comparison with the patient's blood group type.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3166398", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The immunohistological distribution of blood group (BG)-related antigens including A, B, H type 2, and sialylated Lex in lung adenocarcinomas was examined using monoclonal antibodies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3560450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Blood group A, B, H, Le, Leb, Lex, and Ley antigenicity as well as the expression of CA 19-9 were examined in pancreatic cancer specimens from 30 patients, using monoclonal antibodies to the respective antigen and immunohistochemical techniques, and the findings were correlated with the blood group types (ABO and Lewis) of the individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3166398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "[Expression of the blood group related antigens (Lewis(a), Lewis(b), Lewis(x), Lewis(y), and other gastroenterological tissue related antigens(CEA, APF, and NSE) in poorly differentiated adenocarcinoma of gastric cancer with medullary growth pattern].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7679772", "endSection": "title" }, { "offsetInBeginSection": 384, "offsetInEndSection": 593, "text": "Foveolar epithelium of normal gastric mucosa has type 1 blood group associated antigen (Lewis(a), Lewis(b)) and deep gland has type 2 antigen (Lewis(x), Lewis(y)) respectively, as the differentiation antigens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7679772", "endSection": "abstract" } ] }, { "body": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9012519", "http://www.ncbi.nlm.nih.gov/pubmed/9114030", "http://www.ncbi.nlm.nih.gov/pubmed/11867225", "http://www.ncbi.nlm.nih.gov/pubmed/9744863", "http://www.ncbi.nlm.nih.gov/pubmed/12324650", "http://www.ncbi.nlm.nih.gov/pubmed/10828050", "http://www.ncbi.nlm.nih.gov/pubmed/2040696", "http://www.ncbi.nlm.nih.gov/pubmed/16189270", "http://www.ncbi.nlm.nih.gov/pubmed/10220430", "http://www.ncbi.nlm.nih.gov/pubmed/2362805", "http://www.ncbi.nlm.nih.gov/pubmed/11567985" ], "ideal_answer": [ "The expression of genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR) Targeted deletion of 5'HS1 and 5\u2019HS4 of the beta-globin locus Control region reveals additive activity of the sites . The LCR is composed of a series of 5 DNase . sites (5'HSs), that form in the nucleus of erythroid precursors .", "Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals. The LCR encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors.", "Mammalian beta-globin loci is composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated . Globin gene expression is regulated by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR) The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals .", "The expression of genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR) The LCR is composed of a series of 5 DNase . sites (5'HSs), that form in the nucleus of erythroid precursors . In the chromatin of the epsilon globin gene, four DNase. sites that are located 6-18kb 5' of the . epsilon, Ggamma, Agamma, delta, beta .", "Mammalian beta-globin expression is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major HSs, termed 5'HS1-5, located 6-22 Kb upstream of the epsilon-globin gene, each of which is highly homologous among humans, mice, and other mammals.", "Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. Globin gene expression is regulated, in part, by the locus control region, which physically consists of five DNaseI-hypersensitive sites located 6-22 Kb upstream of the epsilon -globin gene.", "In the chromatin of erythroid cells the locus control region is characterized by four DNaseI hypersensitive sites that are located 6-18kb 5' of the epsilon globin gene . Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by a linked 15-kilobase region ." ], "exact_answer": [ "5", "five" ], "type": "factoid", "id": "5fe08b50a43ad31278000031", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 469, "text": "Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10828050", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 316, "text": "The LCR encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16189270", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 490, "text": "Globin gene expression is regulated, in part, by the locus control region, which physically consists of five DNaseI-hypersensitive sites located 6-22 Kb upstream of the epsilon -globin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12324650", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 617, "text": "he LCR is composed of a series of 5 DNaseI hypersensitive sites (5'HSs) that form in the nucleus of erythroid precursors. These HSs are conserved among mammals, bind transcription factors that also bind to other parts of the locus, and compose the functional components of the LCR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11567985", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 728, "text": "n addition, we have identified DNaseI-hypersensitive sites within the newly sequenced regions in both mouse and human, and these structural features also are conserved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10220430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The human beta-globin locus control region (LCR) consists of four erythroid-specific DNaseI hypersensitive sites (HSs) at the 5' end of the beta-globin cluster. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9114030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The beta-globin locus control region (LCR) is contained on a 20 kb DNA fragment and is characterized by the presence of five DNaseI hypersensitive sites in erythroid cells, termed 5'HS1-5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9012519", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 417, "text": "In the chromatin of erythroid cells the locus control region is characterized by four DNaseI hypersensitive sites that are located 6-18 kb 5' of the epsilon globin gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2040696", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 729, "text": "The results show that at least three of the individual DNaseI hypersensitive site regions (sites 1, 2 and 3), though expressing at lower levels than the full DCR, are capable of position independent, copy number dependent expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2362805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Targeted deletion of 5'HS1 and 5'HS4 of the beta-globin locus control region reveals additive activity of the DNaseI hypersensitive sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11567985", "endSection": "title" }, { "offsetInBeginSection": 334, "offsetInEndSection": 456, "text": "The LCR is composed of a series of 5 DNaseI hypersensitive sites (5'HSs) that form in the nucleus of erythroid precursors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11567985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The beta-globin locus control region (LCR) is contained on a 20 kb DNA fragment and is characterized by the presence of five DNaseI hypersensitive sites in erythroid cells, termed 5'HS1-5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9012519", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 469, "text": "The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10828050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The locus control region of the beta-globin cluster contains five DNase I hypersensitive sites (5'HS1-5) required for locus activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9744863", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 233, "text": "Several major DNase hypersensitive sites (HSs 1-5) mark the LCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11867225", "endSection": "abstract" } ] }, { "body": "What is the outcome of COVID-19 patients treated with tocilizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33262810" ], "ideal_answer": [ "Preliminary clinical results have indicated that tocilizumab can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile." ], "type": "summary", "id": "60259b661cb411341a0000b2", "snippets": [ { "offsetInBeginSection": 397, "offsetInEndSection": 674, "text": " Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33262810", "endSection": "abstract" } ] }, { "body": "Which loss-of-function ABCC8 mutation is associated with Pulmonary Arterial Hypertension (PAH)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30354297" ], "ideal_answer": [ "A de novo novel heterozygous predicted deleterious missense variant c.G2873A (p.R958H) in ABCC8 in a child with idiopathic PAH." ], "exact_answer": [ "c.G2873A", "p.R958H" ], "type": "factoid", "id": "5e2e1986fbd6abf43b000025", "snippets": [ { "offsetInBeginSection": 399, "offsetInEndSection": 1563, "text": "Exome sequencing was performed to identify novel genes in a cohort of 99 pediatric and 134 adult-onset group I PAH patients. Novel rare variants in the gene identified were independently identified in a cohort of 680 adult-onset patients. Variants were expressed in COS cells and function assessed by patch-clamp and rubidium flux analysis.RESULTS: We identified a de novo novel heterozygous predicted deleterious missense variant c.G2873A (p.R958H) in ABCC8 in a child with idiopathic PAH. We then evaluated all individuals in the original and a second cohort for rare or novel variants in ABCC8 and identified 11 additional heterozygous predicted damaging ABCC8 variants. ABCC8 encodes SUR1 (sulfonylurea receptor 1)-a regulatory subunit of the ATP-sensitive potassium channel. We observed loss of ATP-sensitive potassium channel function for all ABCC8 variants evaluated and pharmacological rescue of all channel currents in vitro by the SUR1 activator, diazoxide.CONCLUSIONS: Novel and rare missense variants in ABCC8 are associated with PAH. Identified ABCC8 mutations decreased ATP-sensitive potassium channel function, which was pharmacologically recovered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30354297", "endSection": "abstract" } ] }, { "body": "Which disease is rated using the Fahn-Tolosa-Marin scale?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30045955", "http://www.ncbi.nlm.nih.gov/pubmed/16235669", "http://www.ncbi.nlm.nih.gov/pubmed/12722174", "http://www.ncbi.nlm.nih.gov/pubmed/31974808", "http://www.ncbi.nlm.nih.gov/pubmed/28665251", "http://www.ncbi.nlm.nih.gov/pubmed/29385927", "http://www.ncbi.nlm.nih.gov/pubmed/28326650", "http://www.ncbi.nlm.nih.gov/pubmed/30363460", "http://www.ncbi.nlm.nih.gov/pubmed/31868685", "http://www.ncbi.nlm.nih.gov/pubmed/25247107", "http://www.ncbi.nlm.nih.gov/pubmed/29157315", "http://www.ncbi.nlm.nih.gov/pubmed/29376092", "http://www.ncbi.nlm.nih.gov/pubmed/31559624", "http://www.ncbi.nlm.nih.gov/pubmed/31323173", "http://www.ncbi.nlm.nih.gov/pubmed/30565036", "http://www.ncbi.nlm.nih.gov/pubmed/29777361", "http://www.ncbi.nlm.nih.gov/pubmed/10461102", "http://www.ncbi.nlm.nih.gov/pubmed/30122598", "http://www.ncbi.nlm.nih.gov/pubmed/25527389", "http://www.ncbi.nlm.nih.gov/pubmed/29330020", "http://www.ncbi.nlm.nih.gov/pubmed/31721077", "http://www.ncbi.nlm.nih.gov/pubmed/25471376", "http://www.ncbi.nlm.nih.gov/pubmed/30893720", "http://www.ncbi.nlm.nih.gov/pubmed/29929813", "http://www.ncbi.nlm.nih.gov/pubmed/29530725", "http://www.ncbi.nlm.nih.gov/pubmed/29382631", "http://www.ncbi.nlm.nih.gov/pubmed/28387629", "http://www.ncbi.nlm.nih.gov/pubmed/26982989", "http://www.ncbi.nlm.nih.gov/pubmed/17343274", "http://www.ncbi.nlm.nih.gov/pubmed/20457958", "http://www.ncbi.nlm.nih.gov/pubmed/24038576", "http://www.ncbi.nlm.nih.gov/pubmed/29481820", "http://www.ncbi.nlm.nih.gov/pubmed/28913163", "http://www.ncbi.nlm.nih.gov/pubmed/29293948" ], "ideal_answer": [ "The Fahn-Tolosa-Marin clinical tremor rating scale is used for essential tremor." ], "exact_answer": [ "essential tremor" ], "type": "factoid", "id": "5e46eb7a3f5415952900000d", "snippets": [ { "offsetInBeginSection": 1060, "offsetInEndSection": 1192, "text": "The Fahn-Tolosa-Marin (FTM) clinical tremor rating scale was used to score tremor, drawing, and drinking before and after each GKT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28387629", "endSection": "abstract" }, { "offsetInBeginSection": 1074, "offsetInEndSection": 1189, "text": "The Fahn-Tolosa-Marin clinical tremor rating scale was used to evaluate tremor, handwriting, drawing, and drinking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28665251", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 949, "text": "During each study visit, the Fahn-Tolosa-Marin (FTM) scale, the Unified Parkinson's Disease Rating Scale, and the Quality of Life for Essential Tremor Questionnaire (QUEST) were administered along with kinematic assessment of the treated limb. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157315", "endSection": "abstract" }, { "offsetInBeginSection": 1717, "offsetInEndSection": 1895, "text": "Further, this same network was associated with clinical tremor severity measured with the Fahn, Tolosa, Marin Tremor Rating Scale, suggesting this network is clinically relevant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29293948", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 836, "text": "Results: Postsurgery mean scores for the Fahn-Tolosa-Marin Tremor Scale were improved from 78 to 44 in SCA patients and from 54 to 21 in ET patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29376092", "endSection": "abstract" }, { "offsetInBeginSection": 1709, "offsetInEndSection": 1977, "text": "Secondary objectives include tremor reduction (obtained by the Fahn-Tolosa-Marin tremor rating scale, video recordings, the Unified Parkinson's disease rating scale, and by tremor analysis), psychiatric assessment of patients, and to assess the safety of intervention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382631", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1753, "text": "All the enrolled patients were evaluated before the treatment and 2 days after, with a clinical control of the treatment effectiveness using the graphic items of the Fahn-Tolosa-Marin tremor rating scale. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29385927", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 764, "text": "Thirty-four ET patients were consecutively enrolled in the experiments and assessed along one year. Arm tremor was videofilmed and scored using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29481820", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 695, "text": "Fahn-Tolosa-Marin tremor rating scale was used for tremor evaluation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29530725", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 754, "text": "Tremor and cerebellar signs were scored according to the Fahn-Tolosa-Marin and the SARA scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29777361", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 627, "text": "Tremor severity on acute stimulation was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale. Cerebellar impairment was evaluated with the International Cooperative Ataxia Rating Scale. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30045955", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 863, "text": "The treatment efficacy was evaluated by the Fahn Tolosa Marin tremor rating score and NIH genetic criteria for tremor severity at 4 and 8 weeks after each of the two sets of treatments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29929813", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 881, "text": "Two neurologists rated ET by Fahn-Tolosa Marin Tremor Rating Scale (FTMTRS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30122598", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 446, "text": "JECTIVE: To compare the sensitivity of the Fahn-Tolosa-Marin Tremor Rating Scale, the Part III of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the MDS-UPDRS Tremor Scale to the effects of various antitremor treatments.ME", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868685", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 889, "text": "r functions were rated prior to and after surgery using the revised Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III), the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTM-TRS), and the Unified Dystonia Rating Scale (UDRS). Fur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31323173", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1070, "text": " MEASURES: Clinical outcomes, as measured by the Fahn-Tolosa-Marin Tremor Rating Scale and activities of daily living scores, and incidence of adverse events.RESULTS: Fro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20457958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "[Validation study of the Spanish version of the Fahn-Tolosa-Marin scale for essential tremor].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31559624", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "INTRODUCTION: The Fahn-Tolosa-Marin (FTM) tremor rating scale has been widely used in clinics for the estimation of tremor severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31559624", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1922, "text": "a-Marin Tremor Rating Scale activities of daily living scores improved significantly after GKT (P = .03; median and mean change scores, 2.5 and 2.7 points, respectively [range of scale was 0-27]), but there was no significant improvement in other Fahn-Tolosa-Marin Tremor Rating Scale items (P = .53 for resting tremor, P = .24 for postural tremor, P = .62 for action tremor, P = .40 for drawing, P > .99 for pouring water, P = .89 for head tremor). Handwriting a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20457958", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 889, "text": "inical outcomes were assessed using the Fahn-Tolosa-Marin tremor rating scale at baseline and postoperatively at the time of evaluation. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28326650", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1094, "text": "S: Part B of the Fahn-Tolosa-Marin Tremor Rating Scale was the most sensitive to acute levodopa challenge (Cohen's d\u200a=\u200a-1.04, \u03b72\u200a=\u200a0.12). Howev", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868685", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 760, "text": "emor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale and/or the Unified Parkinson's Disease Rating Scale.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29330020", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 346, "text": "THODS: Clinical outcomes were evaluated in 19 patients who had undergone DBS surgery by using the Fahn-Tolosa-Marin clinical tremor rating scale. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16235669", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 419, "text": "and after surgery, PD patients were evaluated using the Unified PD Rating Scale (UPDRS), and ET patients were evaluated using the Fahn-Tolosa-Marin (FTM) tremor rating scale. Inner and to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10461102", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 446, "text": "ter blinded to treatment evaluated Unified Parkinson's Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25247107", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 369, "text": "e studied a cohort of 125 consecutive patients treated with valproate due to epilepsy or migraine, evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). A to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31721077", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 647, "text": "was evaluated using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) in ET patients. The patients wi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25527389", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1042, "text": " was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and the Lower Extremity Clinical Tremor Assessment Scale (LECTAS). A significant diffe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30565036", "endSection": "abstract" }, { "offsetInBeginSection": 786, "offsetInEndSection": 865, "text": " evaluated using the Fahn-Tolosa-Marin Tremor Rating Scale. Poor sleep quality,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25471376", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 630, "text": "rity was assessed using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and tremor amplitude and frequency were evaluated using kinematic techniques. Cognitive prof", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974808", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 772, "text": "sessments included global improvement, Fahn Tolosa Marin Tremor Rating Scale, Beck Depression Inventory and the Parkinson's Disease Questionnaire-39. Patient globa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12722174", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 391, "text": "tients. Methods: The clinical and imaging data of HT patients in 5 teaching hospitals between January 2014 and January 2018 were retrospectively analyzed, and Fahn-Tolosa-Marin Tremor Rating Scale (TRS) was used to compare the clinical severity and short-term prognosis between the differen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30893720", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 767, "text": " and all the other brain areas. These measures were then correlated with the tremor severity evaluated by the Fahn-Tolosa-Marin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28913163", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 446, "text": "o compare the sensitivity of the Fahn-Tolosa-Marin Tremor Rating Scale, the Part III of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the MDS-UPDRS Tremor Scale to the effects of various antitremor treatments.ME", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868685", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1091, "text": "t B of the Fahn-Tolosa-Marin Tremor Rating Scale was the most sensitive to acute levodopa challenge (Cohen's d\u200a=\u200a-1.04, \u03b72\u200a=\u200a0.12). Ho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868685", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1334, "text": "ever, Part A of the Fahn-Tolosa-Marin Tremor Rating Scale showed the highest effect size, which was a small one (Cohen's d\u200a=\u200a-0.33, \u03b72\u200a=\u200a0.03), for detecting a treatment-related change in the severity of tremor during long-term follow-up.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Background: The Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM) has been used in large trials for essential tremor (ET), but its anchors for ratings from 0 to 4 of upper limb tremor are probably too low for patients with severe tremor (tremor amplitude >4 c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30363460", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 406, "text": "Before and after surgery, PD patients were evaluated using the Unified PD Rating Scale (UPDRS), and ET patients were evaluated using the Fahn-Tolosa-Marin (FTM) tremor rating scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10461102", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 631, "text": "Tremor rate was evaluated using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) in ET patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25527389", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 402, "text": "Methods: The clinical and imaging data of HT patients in 5 teaching hospitals between January 2014 and January 2018 were retrospectively analyzed, and Fahn-Tolosa-Marin Tremor Rating Scale (TRS) was used to compare the clinical severity and short-term prognosis between the different subtypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30893720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "INTRODUCTION: The Fahn-Tolosa-Marin (FTM) tremor rating scale has been widely used in clinics for the estimation of tr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31559624", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1417, "text": "Five tremor severity scales (the Fahn-Tolosa-Marin Tremor Rating Scale, the Bain and Findley Clinical Tremor Rating Scale, the Bain and Findley Spirography Scale, the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale, and the Tremor Research Group Essential Tremor Rating Assessment Scale), one ADL/disability scale (the Bain and Findley Tremor ADL Scale), one quality-of-life scale (the Quality of Life in Essential Tremor Questionnaire), and one screening instrument (the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale, version 1) are recommended using these criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24038576", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 612, "text": "All participants were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale for the severity of tremor; a neuropsychological assessment battery and a screening questionnaire for mood and anxiety symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26982989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The purpose of this study was to evaluate interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) in essential tremor (ET).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17343274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17343274", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Comparison of the Fahn-Tolosa-Marin Clinical Rating Scale and the Essential Tremor Rating Assessment Scale.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30363460", "endSection": "title" } ] }, { "body": "List the core SNARE complex proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29548989", "http://www.ncbi.nlm.nih.gov/pubmed/28426820" ], "ideal_answer": [ "VAMP2\nSyntaxin\nSNAP25" ], "exact_answer": [ [ "VAMP2" ], [ "Syntaxin" ], [ "SNAP25" ] ], "type": "list", "id": "5e9202c52d3121100d000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "SNAP-25 is a protein involved in regulated membrane fusion and part of the SNARE complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29548989", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 352, "text": "SNAP-25 together with Syntaxin 1 and VAMP-2 forms the ternary SNARE complex essential for mediating activity-dependent release of hormones and neurotransmitters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29548989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is composed of three neuronal proteins VAMP2, Syntaxin and SNAP25, which plays a core role during the process of membrane fusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28426820", "endSection": "abstract" } ] }, { "body": "What is septicemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9691728", "http://www.ncbi.nlm.nih.gov/pubmed/28711436" ], "ideal_answer": [ "Septicemia occurs when a bacterial infection elsewhere in the body, such as the lungs or skin, enters the bloodstream." ], "type": "summary", "id": "5e64eef51af46fc130000016", "snippets": [ { "offsetInBeginSection": 24, "offsetInEndSection": 201, "text": "Rapid identification of microbes in the bloodstream is crucial in managing septicemia because of its high disease severity, and direct identification from positive blood culture", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28711436", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 916, "text": "The definition of septicemia according to Schottm\u00fcller (1914), as a generalized bacterial infection with a persistent bacteremia is still justified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9691728", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1130, "text": "The term \"sepsis\" has become ambiguous because it has been used as synonym of \"acute response to infection\", while in the past and presently, at least in Europe, it is synonym of septicemia, persistent bacteremia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9691728", "endSection": "abstract" } ] }, { "body": "Which is the master oncogenic transcription factor in T-cell acute lymphoblastic leukemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28028313", "http://www.ncbi.nlm.nih.gov/pubmed/27550837", "http://www.ncbi.nlm.nih.gov/pubmed/32633635", "http://www.ncbi.nlm.nih.gov/pubmed/28652130", "http://www.ncbi.nlm.nih.gov/pubmed/29326336", "http://www.ncbi.nlm.nih.gov/pubmed/9507011", "http://www.ncbi.nlm.nih.gov/pubmed/14604958", "http://www.ncbi.nlm.nih.gov/pubmed/30145780", "http://www.ncbi.nlm.nih.gov/pubmed/22897851", "http://www.ncbi.nlm.nih.gov/pubmed/28179281", "http://www.ncbi.nlm.nih.gov/pubmed/23263491" ], "ideal_answer": [ "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell Acute lymphoblastic Leukemia (T-ALL) cells.", "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-Cell Acute lymphoblastic Leukemia (T-ALL) cells.", "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell Acute lymphoblastic Leukemia (T-ALL) cells. It's not the master transcription factor, it's the oncogene.", "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells." ], "exact_answer": [ "TAL1" ], "type": "factoid", "id": "5fe31312a43ad31278000042", "snippets": [ { "offsetInBeginSection": 422, "offsetInEndSection": 747, "text": "We identify CNOT3 as a tumor suppressor mutated in 7 of 89 (7.9%) adult T-ALLs, and its knockdown causes tumors in a sensitized Drosophila melanogaster model. In addition, we identify mutations affecting the ribosomal proteins RPL5 and RPL10 in 12 of 122 (9.8%) pediatric T-ALLs, with recurrent alterations of Arg98 in RPL10.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23263491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29326336", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29326336", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1462, "text": "Our results indicate that ARID5B reinforces the oncogenic transcriptional program by positively regulating the TAL1-induced regulatory circuit and MYC in T-ALL, thereby contributing to T-cell leukemogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29326336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "TAL1 as a master oncogenic transcription factor in T-cell acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28652130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "BACKGROUND: T-cell acute lymphoblastic leukemia is a hematologic malignancy characterized by T-cell proliferation, and in many cases, the ectopic expression of the oncogenic transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32633635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32633635", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Aberrant expression of transcription factor oncogenes such as HOX11, HOX11L2, TAL1/SCL, LYL1, LMO1, and LMO2 can be detected in lymphoblasts from up to 80% of patients with acute T-cell lymphoblastic leukemia (T-ALL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14604958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The transcription factor TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL), a malignant disorder resulting from leukemic transformation of thymus T-cell precursors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28028313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "TAL1 as a master oncogenic transcription factor in T-cell acute lymphoblastic leukemia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28652130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "The transcription factor TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL), a malignant disorder resulting from leukemic transformation of thymus T-cell precursors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28028313", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T\u00a0cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22897851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The Tal1 oncogene is a class II basic helix-loop-helix (bHLH) transcription factor, overexpressed in as much as 60% of T cell acute lymphoblastic leukemia cases. Li", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9507011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "SCL/TAL1 (stem cell leukemia/T-cell acute lymphoblastic leukemia [T-ALL] 1) is an essential transcription factor in normal and malignant hematopoiesis. It", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28179281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Previous results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27550837", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1606, "text": "In this review, we focus on the oncogenic transcription factor TAL1 and the tumor-suppressor E-proteins and discuss the malignant cell state, the transcriptional circuit, and the consequence of molecular abnormalities in T-ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28652130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T\u00a0cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22897851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Oncogenic transcriptional program driven by TAL1 in T-cell acute lymphoblastic leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145780", "endSection": "title" } ] }, { "body": "List as many European influenza vaccines as possible.", "_type": "yesno", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8801083" ], "_body": "\"DPM1001\"", "ideal_answer": [ "Three split-virion vaccines (Vaxigrip, Begrivac, and Influsplit/Fluarix) and three subunit vaccines containing only viral surface glycoproteins (Influvac, Agrippal, and Fluvirin)." ], "exact_answer": [ [ "Vaxigrip" ], [ "Begrivac" ], [ "Influsplit", "Fluarix" ], [ "Influvac" ], [ "Agrippal" ], [ "Fluvirin" ] ], "type": "list", "id": "5e29f732aa19d74431000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Three split-virion vaccines (Vaxigrip, Begrivac, and Influsplit/Fluarix) and three subunit vaccines containing only viral surface glycoproteins (Influvac, Agrippal, and Fluvirin) available for the 1994-95 season were analysed by biological, molecular, and biochemical methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8801083", "endSection": "abstract" } ] }, { "body": "What is canSAR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26673713", "http://www.ncbi.nlm.nih.gov/pubmed/30496479", "http://www.ncbi.nlm.nih.gov/pubmed/24304894", "http://www.ncbi.nlm.nih.gov/pubmed/22013161" ], "ideal_answer": [ "canSAR (http://cansar.icr.ac.uk) is a public integrative cancer-focused knowledgebase for the support of cancer translational research and drug discovery. Through the integration of biological, pharmacological, chemical, structural biology and protein network data, it provides a single information portal to answer complex multidisciplinary questions including--among many others--and what is known about a protein, in which cancers is it expressed or mutated, and what chemical tools and cell line models can be used to experimentally probe its activity.", "canSAR (http://cansar.icr.ac.uk) is a freely available, multidisciplinary, cancer-focused knowledgebase developed to support cancer translational research and drug discovery . It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessments .", "canSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowlegebase. canSAR informs researchers to help solve key bottlenecks in cancer translation and drug discovery. It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessments. canSAR is widely used internationally by academia and industry.", "CanSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowledgebase. It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessment. canSAR is widely used worldwide by professors, biologists and scientists interested in the molecular biology of cancer, in particular with regard to translation-dependent and -independent pathways of cancer progression." ], "type": "summary", "id": "5e2b2d4afbd6abf43b000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 477, "text": "canSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowlegebase. canSAR informs researchers to help solve key bottlenecks in cancer translation and drug discovery. It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessments. canSAR is widely used internationally by academia and industry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30496479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 453, "text": "canSAR (http://cansar.icr.ac.uk) is a publicly available, multidisciplinary, cancer-focused knowledgebase developed to support cancer translational research and drug discovery. canSAR integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and druggability data. canSAR is widely used to rapidly access information and help interpret experimental data in a translational and drug discovery context.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 999, "text": "canSAR is a fully integrated cancer research and drug discovery resource developed to utilize the growing publicly available biological annotation, chemical screening, RNA interference screening, expression, amplification and 3D structural data. Scientists can, in a single place, rapidly identify biological annotation of a target, its structural characterization, expression levels and protein interaction data, as well as suitable cell lines for experiments, potential tool compounds and similarity to known drug targets. canSAR has, from the outset, been completely use-case driven which has dramatically influenced the design of the back-end and the functionality provided through the interfaces. The Web interface at http://cansar.icr.ac.uk provides flexible, multipoint entry into canSAR. This allows easy access to the multidisciplinary data within, including target and compound synopses, bioactivity views and expert tools for chemogenomic, expression and protein interaction network data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22013161", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 689, "text": "canSAR (http://cansar.icr.ac.uk) is a public integrative cancer-focused knowledgebase for the support of cancer translational research and drug discovery. Through the integration of biological, pharmacological, chemical, structural biology and protein network data, it provides a single information portal to answer complex multidisciplinary questions including--among many others--what is known about a protein, in which cancers is it expressed or mutated, and what chemical tools and cell line models can be used to experimentally probe its activity? What is known about a drug, its cellular sensitivity profile and what proteins is it known to bind that may explain unusual bioactivity?", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304894", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of magrolimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32038992", "http://www.ncbi.nlm.nih.gov/pubmed/33279177" ], "ideal_answer": [ "Magrolimab is an anti-CD47 antibody with promising results for myelodysplastic syndromes and acute myeloid leukemia." ], "type": "summary", "id": "601c13a91cb411341a00000a", "snippets": [ { "offsetInBeginSection": 648, "offsetInEndSection": 877, "text": "Magrolimab, an anti-CD47 antibody, has shown proof-of-principle of efficacy in this therapeutic class with promising early results in both higher risk myelodysplastic syndromes (MDS) and TP53 mutant acute myeloid leukemia (AML). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33279177", "endSection": "abstract" }, { "offsetInBeginSection": 1041, "offsetInEndSection": 1186, "text": "In addition, initial clinical data of CD47 targeting in AML/MDS will be reviewed, and including the first-in-class anti-CD47 antibody magrolimab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32038992", "endSection": "abstract" } ] }, { "body": "List types of mutations.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29115104", "http://www.ncbi.nlm.nih.gov/pubmed/29878242", "http://www.ncbi.nlm.nih.gov/pubmed/27722982" ], "ideal_answer": [ "point mutations\ndeletions\ninsertions\ninversions\ntranslocations" ], "exact_answer": [ [ "point mutations" ], [ "deletions" ], [ "insertions" ], [ "inversions" ], [ "translocations" ] ], "type": "list", "id": "5e91ffc22d3121100d000002", "snippets": [ { "offsetInBeginSection": 268, "offsetInEndSection": 397, "text": "NGS is utilized to novel diagnostic and rare cancer mutations, detection of translocations, inversions, insertions and deletions,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27722982", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 209, "text": "Deletions are the most common types of mutations in \u03b1-thal, followed by point mutations and small insertion/deletion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29115104", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1030, "text": "qEva-CRISPR detects all types of mutations, including point mutations and large deletions, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29878242", "endSection": "abstract" } ] }, { "body": "HER-2 belongs to what family of proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11785652", "http://www.ncbi.nlm.nih.gov/pubmed/12767812", "http://www.ncbi.nlm.nih.gov/pubmed/30312728", "http://www.ncbi.nlm.nih.gov/pubmed/10480346", "http://www.ncbi.nlm.nih.gov/pubmed/25620423", "http://www.ncbi.nlm.nih.gov/pubmed/33202212", "http://www.ncbi.nlm.nih.gov/pubmed/30384340", "http://www.ncbi.nlm.nih.gov/pubmed/11180765", "http://www.ncbi.nlm.nih.gov/pubmed/16800251", "http://www.ncbi.nlm.nih.gov/pubmed/19279475", "http://www.ncbi.nlm.nih.gov/pubmed/18505086", "http://www.ncbi.nlm.nih.gov/pubmed/27993109", "http://www.ncbi.nlm.nih.gov/pubmed/21805036", "http://www.ncbi.nlm.nih.gov/pubmed/22505536", "http://www.ncbi.nlm.nih.gov/pubmed/11694782", "http://www.ncbi.nlm.nih.gov/pubmed/17867585", "http://www.ncbi.nlm.nih.gov/pubmed/16707458", "http://www.ncbi.nlm.nih.gov/pubmed/17536308", "http://www.ncbi.nlm.nih.gov/pubmed/29389942", "http://www.ncbi.nlm.nih.gov/pubmed/15173008", "http://www.ncbi.nlm.nih.gov/pubmed/15920544", "http://www.ncbi.nlm.nih.gov/pubmed/26545934", "http://www.ncbi.nlm.nih.gov/pubmed/27426127", "http://www.ncbi.nlm.nih.gov/pubmed/19048033", "http://www.ncbi.nlm.nih.gov/pubmed/15782071", "http://www.ncbi.nlm.nih.gov/pubmed/7612897", "http://www.ncbi.nlm.nih.gov/pubmed/21896992" ], "ideal_answer": [ "Her-2 belongs to the family of the human epidermal growth factor receptors (EGFRs).", "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER3, HER4, HER5, and HER6.", "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, HER6, and HER8.", "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, and HER6.", "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, HER6, HER7, HER8, and HER9.", "HER-2 is also known as human epidermal growth factor receptor 2 and is a member of the Epidermal growth factor receptor (EGFR) family, members of which are: EGFR, HER2, HER3, and HER4.", "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, HER6, HER7, and HER8.", "Her-2 belongs to the human epidermal growth factor receptor 2 (EGF) family of proteins.", "Herceptin-2 belongs to the human epidermal growth factor receptor 2 (HER2) family of proteins." ], "exact_answer": [ "Epidermal growth factor receptor family" ], "type": "factoid", "id": "5e639a0a1af46fc130000010", "snippets": [ { "offsetInBeginSection": 308, "offsetInEndSection": 357, "text": " human epidermal growth factor receptor-2 (HER2) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30312728", "endSection": "abstract" }, { "offsetInBeginSection": 58, "offsetInEndSection": 100, "text": "epidermal growth factor receptor 2 (HER2) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27993109", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 148, "text": " human epidermal growth factor receptor 2 (HER2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30384340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21896992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The human epidermal growth factor (EGF) receptor (HER) family members cooperate in malignancy. Of this family, HER2 does not bind growth factors ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19048033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 482, "text": "The human epidermal growth factor (EGF) receptor (HER) family consists of four receptors that bind to ligands sharing an EGF-like motif. The HER family of receptor tyrosine kinases and their ligands (EGF family) are known to play a significant role in gastrointestinal cancer. In particular, the EGF receptor, HER1, is one of the main candidates for the molecular-targeted therapy of colon cancer, and HER2 is a candidate for the treatment of gastric cancer which overexpresses HER2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21805036", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 107, "text": " The epidermal growth factor family members: EGF, EGFR and the c-erbB-2(HER-2/neu) gene product ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "HER-2 belongs to the ErbB family of receptor tyrosine kinases, which has been implicated in a variety of cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15173008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "HER-2 belongs to a family of four transmembrane receptor tyrosine kinases that mediate growth, differentiation and survival of cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17867585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "HER-2 belongs to the human epidermal growth factor receptor (HER) family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29389942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Her-2/neu belongs to the family of tyrosine kinase transmembrane proteins whose overexpression has been associated with a poor prognosis in patients with breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11785652", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 337, "text": "The HER-2/neu receptor belongs to the family of epidermal growth factor receptors that are crucial in the activation of subcellular signal transduction pathways controlling epithelial cell growth and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17536308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Human epidermal growth factor receptor 2 (HER2) is a member of the HER family of proteins containing four receptor tyrosine kinases. It ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26545934", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 310, "text": "2 protein is a member of the epidermal growth factor family of transmembrane receptors. HER2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16800251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "HER2 (Human Epidermal Growth Factor Receptor 2), also known as ERBB2, CD340, and Neu protooncogene, is a member of the epidermal growth factor receptor (EGRF) family. Members ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Her-2/neu belongs to the family of tyrosine kinase transmembrane proteins whose overexpression has been associated with a poor prognosis in patients with breast cancer. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11785652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c-erbB-2. Its", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10480346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "HER2, a member of the human ErbB protein family belonging to receptor tyrosine kinases, plays important roles in regulating crucial cellular processes, including cell migration, proliferation, and differentiation. A miss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25620423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "HER-2/neu, also known as c-erbB-2/neu, is an oncogene located in chromosome 17 which encodes HER-2/neu, a transmembrane protein belonging to the EGFR family. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The product of the HER-2/neu proto-oncogene, HER2, is the second member of the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors and has been suggested to be a ligand orphan receptor. Ligan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11180765", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 402, "text": "The Human Epidermal growth factor Receptor (HER) family belongs to the RTKs superfamily, and comprises four members: EGFR (epidermal growth factor receptor), HER2, HER3 and HER4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27426127", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Human epidermal growth factor receptor-2 (HER2/erbB-2) belongs to a family of four transmembrane receptors involved in signal transduction pathways that regulate cell growth and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11694782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The human epidermal growth factor receptor (Her) family of receptor tyrosine kinases includes Her-1, Her-2, and Her-3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15782071", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 361, "text": "Her-2/neu/c-erbB-2, a member of the epidermal growth factor receptor family, can be cleaved into a soluble extra cellular domain (ECD) and a membrane-bound stub fragment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12767812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND AND PURPOSE: Erb-B1 (epidermal growth factor receptor, EGFR) and Erb-B2 (HER-2) are two of the best-characterized memb", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19279475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "The human epidermal growth factor receptor (HER) family of receptor tyrosine kinase has been extensively studied in breast cancer; however, systematic studies of EGFR gene amplification and protein overexpression in breast carcinoma are lacking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15920544", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 364, "text": "Protein tyrosine kinases such as HER-2/c-erbB-2 and the epidermal growth factor receptor (EGFR) have been linked specifically to breast cancer, and perturbations of HER-2 affect response to chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7612897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Overexpression of the epidermal growth factor receptor family member Her-2/neu in breast cancer leads to autophosphorylation of the receptor and induction of multiple downstream signaling pathways, including the Akt kinase to nuclear factor-kappaB (NF-kappaB) cascade that is associated with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16707458", "endSection": "abstract" } ] }, { "body": "What is the chemical structure of Etanercept (ETN)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29411222", "http://www.ncbi.nlm.nih.gov/pubmed/26665003", "http://www.ncbi.nlm.nih.gov/pubmed/29887576", "http://www.ncbi.nlm.nih.gov/pubmed/12510367", "http://www.ncbi.nlm.nih.gov/pubmed/23961669", "http://www.ncbi.nlm.nih.gov/pubmed/29020515", "http://www.ncbi.nlm.nih.gov/pubmed/24611432", "http://www.ncbi.nlm.nih.gov/pubmed/24308717", "http://www.ncbi.nlm.nih.gov/pubmed/28638112", "http://www.ncbi.nlm.nih.gov/pubmed/11336570" ], "ideal_answer": [ "Etanercept (ETN) is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites, which form a complex with the plasma membrane protein Enbrel. Etanercept has been tested for treatment of solid cancers, including glioblastoma and neuroblastoma, and liver fibrosis.", "Etanercept (ETN) is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites. Etanercept has the ability to bind to TNF-\u03b1 and TGF-\u03b2, and thus is a potential novel therapeutic option for the treatment of cancer.", "Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites.", "Etanercept has the best retention rate in rheumatic diseases, but is less or not effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis. Etanercept is a highly glycosylated therapeutic Fc-fusion protein that contains multiple N- and O-glycosylation sites.", "Etanercept has the best retention rate in rheumatic diseases, but is less or not effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis. Etanercept is a highly glycosylated therapeutic Fc-fusion protein that contains multiple N- and O-glycosylation sites. Etanercept is a TNF\u03b1 receptor Fc fusion protein used for the treatment of rheumatic disease and psoriasis. Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1.", "Etanercept has the best retention rate in rheumatic diseases, but is less effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis . It possesses three N- and 13 O-glycosylation sites, with multiple N-and-IgG1-N-G sites . It is a fusion protein, composed of the Fc portion of IgG1 and the extracellular domain of the TNF receptor ." ], "type": "summary", "id": "5fe31306a43ad3127800003c", "snippets": [ { "offsetInBeginSection": 412, "offsetInEndSection": 577, "text": "Etanercept has the best retention rate in rheumatic diseases, but is less or not effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24611432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Etanercept is a highly glycosylated therapeutic Fc-fusion protein that contains multiple N- and O-glycosylation sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24308717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Etanercept is a TNF\u03b1 receptor Fc fusion protein used for the treatment of rheumatic disease and psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28638112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29411222", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 569, "text": "Etanercept is a fusion protein, composed of the Fc portion of IgG1 and the extracellular domain of the TNF receptor (p75)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Etanercept is a dimeric genetic recombinant glycoprotein consisting of Fc domain of human Immunoglobulin G1 and the extracellular domain of human tumor necrosis factor (TNF) receptor type II", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29887576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Etanercept (ETN) is a fusion protein of the receptor (CD120b) for tumor necrosis factor (TNF) and the Fc portion of IgG1. A ph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23961669", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 466, "text": "Etanercept (ETN), a recombinant TNF receptor (p75)-Fc fusion protein, competitively inhibits TNF-\u03b1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26665003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Etanercept (ETN) is a fusion protein of the receptor (CD120b) for tumor necrosis factor (TNF) and the Fc portion of IgG1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23961669", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 324, "text": "ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29020515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Etanercept is a dimeric genetic recombinant glycoprotein consisting of Fc domain of human Immunoglobulin G1 and the extracellular domain of human tumor necrosis factor (TNF) receptor type II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29887576", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 570, "text": "Etanercept is a fusion protein, composed of the Fc portion of IgG1 and the extracellular domain of the TNF receptor (p75).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11336570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Etanercept is a protein comprised of the extracellular domains of two TNF receptors attached to a Fc portion of an IgG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12510367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29411222", "endSection": "abstract" } ] }, { "body": "What does bDMARD stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30876919", "http://www.ncbi.nlm.nih.gov/pubmed/29980576", "http://www.ncbi.nlm.nih.gov/pubmed/32370139", "http://www.ncbi.nlm.nih.gov/pubmed/31058442", "http://www.ncbi.nlm.nih.gov/pubmed/31816434", "http://www.ncbi.nlm.nih.gov/pubmed/28412711", "http://www.ncbi.nlm.nih.gov/pubmed/31171315", "http://www.ncbi.nlm.nih.gov/pubmed/26404390", "http://www.ncbi.nlm.nih.gov/pubmed/24741293", "http://www.ncbi.nlm.nih.gov/pubmed/30799358", "http://www.ncbi.nlm.nih.gov/pubmed/29649840", "http://www.ncbi.nlm.nih.gov/pubmed/32494334" ], "ideal_answer": [ "bDMARDs are biologic disease-modifying antirheumatic drugs." ], "exact_answer": [ "biologic disease-modifying antirheumatic drugs" ], "type": "factoid", "id": "602598201cb411341a0000af", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 148, "text": "Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31058442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "In the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32370139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "The introduction of biological disease-modifying antirheumatic drug (bDMARD) treatments for various types of autoimmune arthritis, such as rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis, represents a new era of treatment for patients with a refractory response to conventional synthetic DMARDs (csDMARDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30876919", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 202, "text": "To establish in a global setting the relationships between countries' socioeconomic status (SES), measured biological disease modifying antirheumatic drug (bDMARD)-usage and disease outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29980576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Biologic disease-modifying antirheumatic drugs (bDMARDs) are engineered proteins with high affinity for various proinflammatory immune mediators to reduce inflammation and its sequelae in various rheumatic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are used in pregnant patients with rheumatic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31816434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29649840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Biologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated with 3 Classes of Intravenous bDMARD.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28412711", "endSection": "title" }, { "offsetInBeginSection": 377, "offsetInEndSection": 913, "text": "Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24741293", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 261, "text": "Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological DMARDs (bDMARDs), and tofacitinib, a targeted sDMARD, can be used to treat RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26404390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Outcomes with Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) in Older Patients Treated for Rheumatoid Arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32494334", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Objective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30799358", "endSection": "abstract" } ] }, { "body": "Is there any role of genotoxic pks + E. coli in cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32106218" ], "ideal_answer": [ "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cancer.", "Yes. A distinct mutational signature in colorectal cancer was described which implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.", "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cell death.", "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cell death and cell death.", "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cell death and cancer." ], "exact_answer": "yes", "type": "yesno", "id": "601d75281cb411341a000043", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Mutational signature in colorectal cancer caused by genotoxic pks+", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32106218", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1144, "text": "Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+ E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32106218", "endSection": "abstract" } ] }, { "body": "Should tirilazad be used for treatment of ischemic stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10978061", "http://www.ncbi.nlm.nih.gov/pubmed/18810661", "http://www.ncbi.nlm.nih.gov/pubmed/11781420" ], "ideal_answer": [ "No. Tirilazad should not be used for treatment of stroke because it does not improve disease outcomes, but may increase death and disability." ], "exact_answer": "no", "type": "yesno", "id": "5e44c59848dab47f26000021", "snippets": [ { "offsetInBeginSection": 1424, "offsetInEndSection": 1553, "text": "CONCLUSION: Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18810661", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1251, "text": "Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89-1.20) or cerebral infarction (OR 1.04, 95% CI 0.89-1.22). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18810661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "The authors investigated whether the lack of effect of tirilazad on clinical outcome in patients with acute ischemic stroke is explained by failure of tirilazad to reduce infarct volume. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11781420", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1546, "text": "Tirilazad did not alter early case fatality (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.79 to 1.56) or end-of-trial case fatality (OR 1.12, 95% CI 0.88 to 1.44). A just-significant increase in death and disability, assessed as either the expanded Barthel Index (OR 1.23, 95% CI 1.01 to 1.51) or Glasgow Outcome Scale (OR 1. 23, 95% CI 1.01 to 1.50) was observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10978061", "endSection": "abstract" }, { "offsetInBeginSection": 1987, "offsetInEndSection": 2314, "text": "CONCLUSIONS: Tirilazad mesylate increases death and disability by about one fifth when given to patients with acute ischemic stroke. Although further trials of tirilazad are now unwarranted, analysis of individual patient data from the trials may help elucidate why tirilazad appears to worsen outcome in acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10978061", "endSection": "abstract" } ] }, { "body": "List the major families of Histones.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26846354", "http://www.ncbi.nlm.nih.gov/pubmed/20194426", "http://www.ncbi.nlm.nih.gov/pubmed/21829453" ], "ideal_answer": [ "Five histone families (H1, H2A, H2B, H3, and H4)." ], "exact_answer": [ [ "H1" ], [ "H2A" ], [ "H2B" ], [ "H3" ], [ "H4" ] ], "type": "list", "id": "5e9208da2d3121100d00000a", "snippets": [ { "offsetInBeginSection": 38, "offsetInEndSection": 86, "text": "five histone families (H1, H2A, H2B, H3, and H4)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20194426", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 56, "text": "H2A, H2B, H3 and H4 histone families", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21829453", "endSection": "abstract" }, { "offsetInBeginSection": 903, "offsetInEndSection": 968, "text": "six for H1, 11 for H2A, eight for H2B, five for H3 and two for H4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26846354", "endSection": "abstract" } ] }, { "body": "Is the Paramyxovirus geneome segmented, negative-sense RNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10400712", "http://www.ncbi.nlm.nih.gov/pubmed/19493999", "http://www.ncbi.nlm.nih.gov/pubmed/28508218", "http://www.ncbi.nlm.nih.gov/pubmed/9525637", "http://www.ncbi.nlm.nih.gov/pubmed/25683441", "http://www.ncbi.nlm.nih.gov/pubmed/24501400", "http://www.ncbi.nlm.nih.gov/pubmed/16325221", "http://www.ncbi.nlm.nih.gov/pubmed/10482624", "http://www.ncbi.nlm.nih.gov/pubmed/9568033", "http://www.ncbi.nlm.nih.gov/pubmed/25948749", "http://www.ncbi.nlm.nih.gov/pubmed/22892200", "http://www.ncbi.nlm.nih.gov/pubmed/29992955", "http://www.ncbi.nlm.nih.gov/pubmed/23707921", "http://www.ncbi.nlm.nih.gov/pubmed/25831513", "http://www.ncbi.nlm.nih.gov/pubmed/28601688" ], "ideal_answer": [ "The paramyxovirus family has a genome consisting of a SINGLE STRAND of negative sense RNA", "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA.", "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA" ], "exact_answer": "no", "type": "yesno", "id": "5e64f11a1af46fc130000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25683441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The avian paramyxovirus type 1 (APMV-1), or Newcastle disease virus (NDV), comprise a diverse group of viruses with a single-stranded, negative-sense RNA genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22892200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Members of the Paramyxoviridae such as measles, mumps, and parainfluenza viruses have pleomorphic, enveloped virions that contain negative-sense unsegmented RNA genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19493999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24501400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "UNLABELLED: Mumps virus (MuV) is a paramyxovirus with a negative-sense nonsegmented RNA genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25948749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Paramyxoviridae, a large family of enveloped viruses harboring a nonsegmented negative-sense RNA\u00a0genome, include important human pathogens as measles, mumps, respiratory syncytial virus (RSV), parainfluenza\u00a0viruses, and henipaviruses, which cause some of the deadliest emerging zoonoses. There ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29992955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25831513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions. These", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9525637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "The replication of nonsegmented minus-strand RNA genomes, like that of Sendai paramyxovirus (SeV), are controlled by the short leader regions present at each end of the linear genomes and antigenomes; the left and right promoters (PL and PR), respectively. Wil", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9568033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe enc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24501400", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 465, "text": "s viral glycoprotein cytoplasmic domains may play a role in this coordination, we have investigated the importance of the hemagglutinin-neuraminidase (HN) protein cytoplasmic domain in the assembly of the nonsegmented negative-strand RNA paramyxovirus simian virus 5 (SV5). By", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10482624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Beilong virus, a novel paramyxovirus with the largest genome of non-segmented negative-stranded RNA viruses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16325221", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9525637", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 412, "text": "Paramyxovirus particles are pleomorphic, with a lipid envelope, nonsegmented RNA genomes of negative polarity, and densely packed glycoproteins on the virion surface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28601688", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "An alternative method to determine the 5' extremities of non-segmented, negative sense RNA viral genomes using positive replication intermediate 3' tailing: application to two members of the Paramyxoviridae family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23707921", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Simian parainfluenza virus 5 (SV5) is a prototype of the Paramyxoviridae family of nonsegmented negative-sense RNA viruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10400712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Human metapneumovirus (HMPV), a single-stranded negative-sense RNA virus belonging to the family Paramyxoviridae, is associated with respiratory tract illness, primarily in young children and persons with underlying disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28508218", "endSection": "abstract" } ] }, { "body": "Approximately how many genes are contained in the X chromosome's non-pseudoautosomal region (non-PAR)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27869828" ], "ideal_answer": [ "The total number of genes contained in the X chromosome's non- pseudoautosomal region (PAR) is 783.", "There are 783 non-pseudoautosomal region (PAR) X-chromosome genes.", "Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes harbored loss-of-function mutations more frequently in males.", "There are 783 non-pseudoautosomal region X-chromosome genes harbored loss-of-function mutations more frequently in males.", "The number of genes contained in the X chromosome's non-pseudoautosomal region (non-PAR) is 783.", "The number of genes contained in the non- pseudo-autosomal region (PAR) X chromosome is 783." ], "exact_answer": [ "783" ], "type": "factoid", "id": "5d387c20a1e1595105000010", "snippets": [ { "offsetInBeginSection": 388, "offsetInEndSection": 559, "text": "Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes (ATRX, CNKSR2, DDX3X, KDM5C, KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869828", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 685, "text": "Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes (ATRX, CNKSR2, DDX3X, KDM5C, KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males (based on a false discovery rate < 0.1), in comparison to zero of 18,055 autosomal and PAR genes (Fisher's exact P < 0.0001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27869828", "endSection": "abstract" } ] }, { "body": "Does the use of bDMARDs during pregnancy impact neonatal development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31816434" ], "ideal_answer": [ "Exposure to bDMARDs during pregnancy does not seem to interfere with post-natal development up to infancy." ], "exact_answer": "no", "type": "yesno", "id": "602599251cb411341a0000b1", "snippets": [ { "offsetInBeginSection": 1009, "offsetInEndSection": 1115, "text": "Exposure to bDMARDs during pregnancy does not seem to interfere with post-natal development up to infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31816434", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 209, "text": "Long-term follow-up data about newborns exposed to bDMARDs during pregnancy are however scarce. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31816434", "endSection": "abstract" } ] }, { "body": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31949313" ], "ideal_answer": [ "No. The KMT2D missense variants do not cause KS1, they cause a different type of malformations disorder distinct from Kabuki syndrome.", "No. The KMT2D missense variants do not cause KS1, they cause a different type of malformations disorder distinct from Kabuki Syndrome.", "No. The KMT2D missense variants do not cause KS1. They cause a multiple malformations disorder distinct from Kabuki syndrome.", "No. The KMT2D missense variants do not cause KS1. They cause a different type of malformations disorder distinct from Kabuki Syndrome.", "No. The KMT2D missense variants do not cause KS1. They cause a multiple malformations disorder distinct from Kabuki Syndrome.", "No. KMT2D missense variants (MVs) located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome type 1 (KS1). Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism." ], "exact_answer": "no", "type": "yesno", "id": "601d46d61cb411341a000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31949313", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1425, "text": "To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1).METHODS: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism.RESULTS: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to \u0251-helical transition.CONCLUSION: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31949313", "endSection": "abstract" } ] }, { "body": "The NoSAS Score can be used for screening of which disorders?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29518851", "http://www.ncbi.nlm.nih.gov/pubmed/31998424", "http://www.ncbi.nlm.nih.gov/pubmed/29789691", "http://www.ncbi.nlm.nih.gov/pubmed/30050090", "http://www.ncbi.nlm.nih.gov/pubmed/32967411", "http://www.ncbi.nlm.nih.gov/pubmed/30220140", "http://www.ncbi.nlm.nih.gov/pubmed/27321086", "http://www.ncbi.nlm.nih.gov/pubmed/29394959", "http://www.ncbi.nlm.nih.gov/pubmed/31196834", "http://www.ncbi.nlm.nih.gov/pubmed/29055261", "http://www.ncbi.nlm.nih.gov/pubmed/33222029", "http://www.ncbi.nlm.nih.gov/pubmed/32842224", "http://www.ncbi.nlm.nih.gov/pubmed/30233849", "http://www.ncbi.nlm.nih.gov/pubmed/28064432" ], "ideal_answer": [ "The NoSAS score can be used for screening of obstructive sleep apnea syndrome, Sleep-Disordered Breathing and obstructive sleep apnea-hypopnea syndrome." ], "exact_answer": [ [ "obstructive sleep apnea syndrome" ], [ "Sleep-Disordered Breathing" ], [ "obstructive sleep apnea-hypopnea syndrome" ] ], "type": "list", "id": "5e47592835b8f0833c000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "The NoSAS score: A new and simple screening tool for obstructive sleep apnea syndrome in depressive disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29055261", "endSection": "title" }, { "offsetInBeginSection": 196, "offsetInEndSection": 407, "text": "The aim of this study was to assess the effectiveness of the NoSAS score in predicting the presence of OSAS among participants with current MDE and to compare it with the performance of existing screening tools.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29055261", "endSection": "abstract" }, { "offsetInBeginSection": 1500, "offsetInEndSection": 1633, "text": "The NoSAS score is a simple and efficient screening tool for OSAS in this population, and may be a helpful instrument for clinicians.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29055261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Validation of the NoSAS Score for the Screening of Sleep-Disordered Breathing: A Hospital-Based Retrospective Study in China.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29394959", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "STUDY OBJECTIVES: This study was conducted to validate the NoSAS score in clinical populations and to compare it with the Berlin, STOP, and STOP-Bang questionnaires, as well as the Epworth Sleepiness Scale (ESS), in screening for sleep-disordered breathing (SDB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29394959", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1554, "text": "CONCLUSIONS: The NoSAS score is a simple, efficient, and easy method for screening SDB in the clinical setting, especially in moderate to severe SDB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29394959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "[Comparison of the NoSAS score with four different questionnaires as screening tools for obstructive sleep apnea-hypopnea syndrome].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29518851", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Objective: To evaluate the clinical utility of the NoSAS score in the screening of patients with obstructive sleep apnea-hypopnea syndrome(OSAHS), and to compare the performance of the NoSAS score with other tools including Epworth Sleepiness Scale(ESS), STOP, STOP-Bang(SBQ) and Berlin questionnaires. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29518851", "endSection": "abstract" }, { "offsetInBeginSection": 2293, "offsetInEndSection": 2384, "text": "The NoSAS score and the SBQ questionnaire have a moderate performance in diagnosing OSAHS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29518851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Performance of NoSAS score versus Berlin questionnaire for screening obstructive sleep apnoea in patients with resistant hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29789691", "endSection": "title" }, { "offsetInBeginSection": 1299, "offsetInEndSection": 1379, "text": "In conclusion, both BQ and NoSAS score had low accuracy for detecting OSA in RH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29789691", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 605, "text": "All subjects were subjected to clinical evaluation, sleep questionnaires for detecting the risk of OSA (Berlin and NoSAS score), metabolomic analysis by gas chromatography coupled to mass spectrometry and lipidomic analysis with liquid chromatography followed by detection by MALDI-MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30050090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Objective: To evaluate the effect of arterial blood HCO3- level on the accuracy of NoSAS questionnaire screening for obstructive sleep apnea hypopnea syndrome (OSAHS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30220140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Application value of the NoSAS score for screening sleep-disordered breathing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233849", "endSection": "title" }, { "offsetInBeginSection": 100, "offsetInEndSection": 234, "text": "Because of the cost and low availability of these procedures, the NoSAS score was developed to identify subjects at high risk of SDB. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233849", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Validation of NoSAS score for screening of sleep-disordered breathing in a multiethnic Asian population.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28064432", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "PURPOSE: The NoSAS score was developed to identify subjects at high risk of sleep-disordered breathing (SDB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28064432", "endSection": "abstract" }, { "offsetInBeginSection": 1425, "offsetInEndSection": 1674, "text": "CONCLUSIONS: The NoSAS score performed similarly to the STOP-Bang and Berlin questionnaires in a multiethnic Asian cohort. All three questionnaires had high negative predictive values in ruling out severe SDB and may have utility as screening tools.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28064432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27321086", "endSection": "title" }, { "offsetInBeginSection": 1800, "offsetInEndSection": 1961, "text": "INTERPRETATION: The NoSAS score is a simple, efficient, and easy to implement score enabling identification of individuals at risk of sleep-disordered breathing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27321086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Validation of the NoSAS score for screening sleep disordered breathing; A sleep clinic-based study in Turkey.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32967411", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Validation of the NoSAS Score for the Screening of Sleep-Disordered Breathing in a Sleep Clinic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31998424", "endSection": "title" }, { "offsetInBeginSection": 500, "offsetInEndSection": 622, "text": "JECTIVES: To evaluate the performance of the NoSAS score as a screening tool for the diagnosis of OSA in a sleep clinic.ME", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31196834", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 488, "text": "To evaluate the clinical utility of the NoSAS score for screening patients with SDB in China and to compare the predictive value of the NoSAS score with the Epworth Sleepiness Scale (ESS), we used the STOP-Bang questionnaire and the Berlin questionnaire.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233849", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The NoSAS score: A new and simple screening tool for obstructive sleep apnea syndrome in depressive disorder", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29055261", "endSection": "title" }, { "offsetInBeginSection": 1223, "offsetInEndSection": 1394, "text": "g value to OSA. The improved Mallampati grading combined with NoSAS questionnaire can obviously improve the screening sensitivity and specificity of Osa, and has higher ap", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32842224", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1106, "text": "ectively. The sensitivity and specificity of NoSAS combined with improved Mallampati grading for screening OSA were 0.813 and 0.710, res", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32842224", "endSection": "abstract" }, { "offsetInBeginSection": 1819, "offsetInEndSection": 1964, "text": " NoSAS score is a simple, efficient, and easy to implement score enabling identification of individuals at risk of sleep-disordered breathing. Be", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27321086", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1531, "text": "ing a threshold of 8 points or more, the NoSAS score identified individuals at risk of clinically significant sleep-disordered breathing, with an area under the curve (AUC) of 0\u00b774 (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27321086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Objective: To evaluate the clinical utility of the NoSAS score in the screening of patients with obstructive sleep apnea-hypopnea syndrome(OSAHS), and to compare the performance of the NoSAS score with other tools including Epworth Sleepiness Scale(ESS), STOP, STOP-Bang(SBQ) and Berlin questionnaires.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29518851", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1037, "text": "For the questionnaires, the NoSAS score performed best with screening for OSA (area under the curve [AUC]\u2009=\u20090.724, p\u2009=\u20090.003).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30050090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "STUDY OBJECTIVES: This study was conducted to validate the NoSAS score in clinical populations and to compare it with the Berlin, STOP, and STOP-Bang questionnaires, as well as the Epworth Sleepiness Scale (ESS), in screening for sleep-disordere", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29394959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "OBJECTIVES: The NoSAS score has been shown to be a reliable screening tool for obstructive sleep apnea (OSA) in overall ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33222029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Validation of NoSAS (Neck, Obesity, Snoring, Age, Sex) score as a screening tool for obstructive sleep apnea: Analysis in a sleep clinic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31196834", "endSection": "title" } ] }, { "body": "What is the chromosomal abnormality associated with Klinefelter Syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14018845", "http://www.ncbi.nlm.nih.gov/pubmed/17932453", "http://www.ncbi.nlm.nih.gov/pubmed/20172548", "http://www.ncbi.nlm.nih.gov/pubmed/6178494", "http://www.ncbi.nlm.nih.gov/pubmed/28275551", "http://www.ncbi.nlm.nih.gov/pubmed/27408358", "http://www.ncbi.nlm.nih.gov/pubmed/11976824", "http://www.ncbi.nlm.nih.gov/pubmed/29423966", "http://www.ncbi.nlm.nih.gov/pubmed/25973391", "http://www.ncbi.nlm.nih.gov/pubmed/31916730", "http://www.ncbi.nlm.nih.gov/pubmed/30127341", "http://www.ncbi.nlm.nih.gov/pubmed/17077438", "http://www.ncbi.nlm.nih.gov/pubmed/28782868", "http://www.ncbi.nlm.nih.gov/pubmed/16529294", "http://www.ncbi.nlm.nih.gov/pubmed/22486321", "http://www.ncbi.nlm.nih.gov/pubmed/29665107", "http://www.ncbi.nlm.nih.gov/pubmed/29406610", "http://www.ncbi.nlm.nih.gov/pubmed/8203057" ], "ideal_answer": [ "About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY", "About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome)" ], "exact_answer": [ "XXY" ], "type": "factoid", "id": "5e669e0e1af46fc130000019", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 106, "text": "Klinefelter's syndrome is a sex chromosome abnormality affecting approximately 1 in 1000 men. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28782868", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1035, "text": "Klinefelter syndrome (XXY)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30127341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29406610", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 448, "text": "On the other hand, Klinefelter syndrome is well recognized chromosomal abnormality caused by an additional X chromosome in males (47,XXY), and the characteristic clinical findings include tall stature, immaturity of external genitalia, testicular dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932453", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 305, "text": "The formal cytogenetic designation for Klinefelter syndrome is 47, XXY; the extra sex chromosome is due to meiotic chromosomal nondisjunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11976824", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 382, "text": "Klinefelter syndrome (KS) is characterized by an additional X chromosome in males leading to a karyotype of 47,XXY.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31916730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Klinefelter syndrome (KS), a 47,XXY chromosomal abnormality, has been shown to be associated with a number of malignancies, but has not been linked to acute leukemias to date. We p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25973391", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 308, "text": " formal cytogenetic designation for Klinefelter syndrome is 47, XXY; the extra sex chromosome is due to meiotic chromosomal nondisjunction. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11976824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "A case of Klinefelter's syndrome with the development of a mediastinal teratocarcinoma is reported suggesting that the association of a gonadotropin-secreting tumor with the XXY chromosomal abnormality may be more than coincidental.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6178494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Klinefelter syndrome (KS) is a chromosomal abnormality characterised by a 47, XXY karyotype associated with hypogonadism and infertility. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28275551", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 443, "text": "ed. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20172548", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 609, "text": "alysis showed azoospermia, and chromosomal analysis revealed a 47,XY,i(X)(q10) karyotype, which is a rare variant of Klinefelter syndrome. No spermatozoon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29665107", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 457, "text": "the other hand, Klinefelter syndrome is well recognized chromosomal abnormality caused by an additional X chromosome in males (47,XXY), and the characteristic clinical findings include tall stature, immaturity of external genitalia, testicular dysfunction. Here, we", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17932453", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 798, "text": "8 patients, 39(10.9%) were found to have chromosomal abnormalities in which Klinefelter's syndrome (47, XXY) was the most common chromosomal aberration. The incidenc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16529294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Klinefelter syndrome (KS) is a chromosome abnormality characterized by a 47, XXY karyotype associated with hypogonadism and infertility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27408358", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 399, "text": "Klinefelter's syndrome may be associated with a variety of different sex chromosome anomalies including XXY, XXYY, XXXY and XXXXY.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14018845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Klinefelter's syndrome, characterised by a 47,XXY chromosomal pattern, has largely been associated with physical abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17077438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Klinefelter syndrome associated with 13/14 translocation abnormality 46,XXY,t(13q;14q).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8203057", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Klinefelter syndrome is caused by the presence of one or more additional X chromosomes in an affected male.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22486321", "endSection": "abstract" } ] }, { "body": "What distinguishes RIDLs from other transpozable elements?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24850885" ], "ideal_answer": [ "Here, we link these two concepts by proposing that exonic TEs act as RNA domains that are essential for lncRNA function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs).", "One class of sequence elements that is enriched in lncRNA is represented by transposable elements (TEs), repetitive mobile genetic sequences that have contributed to genome evolution through a process termed exaptation. We term such elements Repeat insertion domains of LncRNAs (RIDLs).", "Repeat Insertion Domains of LncRNAs (RIDLs) are exonic TEs that are essential for lncRNA function.", "Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs . A growing number of RIDLs have been experimentally defined, where TE-derived fragments of lncRNA act as RNA-, DNA-, and protein-binding domains . We term such elements Repeat Insertion Domains of LncRNAs (RIDL)", "Exonic TEs act as RNA domains that are essential for lncRNA function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs)" ], "exact_answer": [ "they are exonic" ], "type": "factoid", "id": "5d388192a1e1595105000015", "snippets": [ { "offsetInBeginSection": 524, "offsetInEndSection": 710, "text": "Here, we link these two concepts by proposing that exonic TEs act as RNA domains that are essential for lncRNA function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24850885", "endSection": "abstract" } ] }, { "body": "What indication has FTY720 been approved for by the FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21456524" ], "ideal_answer": [ "FTY720 has been pproved (September 2010) by the U.S. FDA as a new treatment for multiple sclerosis (MS)." ], "exact_answer": [ "multiple sclerosis" ], "type": "factoid", "id": "605271d994d57fd87900000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Fingolimod (FTY720): a recently approved multiple sclerosis drug based on a fungal secondary metabolite.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21456524", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Fingolimod (Gilenya; FTY720), a synthetic compound based on the fungal secondary metabolite myriocin (ISP-I), is a potent immunosuppressant that was approved (September 2010) by the U.S. FDA as a new treatment for multiple sclerosis (MS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21456524", "endSection": "abstract" } ] }, { "body": "Is fingolimod a drug or a pro-drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15265669" ], "ideal_answer": [ "FTY720 is a prodrug." ], "exact_answer": [ "prodrug" ], "type": "factoid", "id": "6053bd5194d57fd879000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "FTY720 is a prodrug for FTY-phosphate, an agonist at four of the five known receptors for sphingosine-1-phosphate (S1P). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15265669", "endSection": "abstract" } ] }, { "body": "Which conditions is caused by mutations in HFE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19146986", "http://www.ncbi.nlm.nih.gov/pubmed/9358014", "http://www.ncbi.nlm.nih.gov/pubmed/17255318", "http://www.ncbi.nlm.nih.gov/pubmed/21175851", "http://www.ncbi.nlm.nih.gov/pubmed/17061732", "http://www.ncbi.nlm.nih.gov/pubmed/15506716", "http://www.ncbi.nlm.nih.gov/pubmed/12874382", "http://www.ncbi.nlm.nih.gov/pubmed/23512844", "http://www.ncbi.nlm.nih.gov/pubmed/17401564", "http://www.ncbi.nlm.nih.gov/pubmed/11939483", "http://www.ncbi.nlm.nih.gov/pubmed/19907151", "http://www.ncbi.nlm.nih.gov/pubmed/15546588", "http://www.ncbi.nlm.nih.gov/pubmed/27081498", "http://www.ncbi.nlm.nih.gov/pubmed/11191743", "http://www.ncbi.nlm.nih.gov/pubmed/18316026", "http://www.ncbi.nlm.nih.gov/pubmed/10226674", "http://www.ncbi.nlm.nih.gov/pubmed/9425935", "http://www.ncbi.nlm.nih.gov/pubmed/20177050", "http://www.ncbi.nlm.nih.gov/pubmed/31529915", "http://www.ncbi.nlm.nih.gov/pubmed/12091366", "http://www.ncbi.nlm.nih.gov/pubmed/19477142", "http://www.ncbi.nlm.nih.gov/pubmed/26501199", "http://www.ncbi.nlm.nih.gov/pubmed/18325820", "http://www.ncbi.nlm.nih.gov/pubmed/19820015", "http://www.ncbi.nlm.nih.gov/pubmed/16154780", "http://www.ncbi.nlm.nih.gov/pubmed/11001626", "http://www.ncbi.nlm.nih.gov/pubmed/28335084", "http://www.ncbi.nlm.nih.gov/pubmed/17065470", "http://www.ncbi.nlm.nih.gov/pubmed/21355094", "http://www.ncbi.nlm.nih.gov/pubmed/28406842", "http://www.ncbi.nlm.nih.gov/pubmed/24904118" ], "ideal_answer": [ "Mutations in the HFE gene, encoding the syntaxin binding protein HFE1, are the cause of hereditary hemochromatosis.", "Hereditary hemochromatosis is an autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage . The vast majority of HH patients are homozygous for the C282Y HFE mutation in HFE . The study was to establish a reliable, cost-effective molecular diagnostic service for this potentially lethal disorder in South Africa . The authors suggest lymphocytes from HH patients may have an increased capacity to respond to DEB-induced chromosome breakage .", "Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage. The vast majority of HH patients are homozygous for the C282Y mutation in HFE.", "Mutations in the HFE gene cause hereditary hemochromatosis, an iron overload disorder that is hallmarked by excessive accumulation of iron in parenchymal organs.", "Hereditary hemochromatosis (HH) is common among Caucasians. Hereditary hemochromatosis patients homozygous for the C282Y HFE mutation.", "Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage. The vast majority of HH patients are homozygous for the C282Y mutation in HFE. HFE mutation can possess the risk of AD in transferrin-, APOE- and APP-normal patients.", "Mutations in HFE, a gene encoding a putative lysosomal trafficking protein, cause hereditary hemochromatosis.", "The mechanisms by which the hereditary hemochromatosis protein, HFE, decreases transferrin-mediated iron uptake were examined Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity Hereditary hemochromatosis (HH) is common among Caucasians; reported disease frequencies vary from 0.3 to 0.8%.", "Mutations in HFE, a gene encoding a putative lysosomal trafficking protein, are the cause of hereditary hemochromatosis.", "HFE, a gene encoding a putative lysosomal trafficking protein, is involved in the pathogenesis of hereditary hemochromatosis." ], "exact_answer": [ "Hemochromatosis", "haemochromatosis", "Hereditary hemochromatosis (HH)" ], "type": "factoid", "id": "5fe0b4cda43ad31278000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The mechanisms by which the hereditary hemochromatosis protein, HFE, decreases transferrin-mediated iron uptake were examined", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12874382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11001626", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Hereditary hemochromatosis (HH) is common among Caucasians; reported disease frequencies vary from 0.3 to 0.8%. Identification of a candidate HFE gene in 1996 was soon followed by the description of two ancestral mutations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11001626", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 355, "text": "The aim of the study was to investigate the molecular basis of hereditary haemochromatosis (HH) in South Africa in order to establish a reliable, cost-effective molecular diagnostic service for this potentially lethal disorder.DESIGN: DNA samples of patient and control groups were screened for two common haemochromatosis (HFE) gene mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10226674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "High prevalence of the Cys282Tyr HFE mutation facilitates an improved diagnostic service for hereditary haemochromatosis in South Africa", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10226674", "endSection": "title" }, { "offsetInBeginSection": 468, "offsetInEndSection": 532, "text": "mutations of HFE, which is a candidate gene for hemochromatosis,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9425935", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 940, "text": "Our data do not confirm an association of PCT with the Cys282Tyr HFE mutation, strongly associated with hemochromatosis in Northern European countries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9425935", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 806, "text": "Haploinsufficiency of HFE may be one possible explanation for hemochromatosis in this patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19477142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Geographic and racial/ethnic differences in HFE mutation frequencies in the Hemochromatosis and Iron Overload Screening", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17061732", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Status of HFE mutation in thalassemia syndromes in north India", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17401564", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Hereditary hemochromatosis is an autosomal recessive and most commonly inherited single gene disorder among Caucasians, with a prevalence of 5 per 1,000 and a carrier frequency of 1 in 10. Two point mutations were described and are referred as C282Y and H63D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17401564", "endSection": "abstract" }, { "offsetInBeginSection": 39, "offsetInEndSection": 112, "text": "hereditary hemochromatosis patients homozygous for the C282Y HFE mutation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19146986", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage. The vast majority of HH patients are homozygous for the C282Y mutation in HFE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19146986", "endSection": "abstract" }, { "offsetInBeginSection": 1769, "offsetInEndSection": 1987, "text": "These results suggest that lymphocytes from HH patients may have an increased capacity to respond to DEB-induced chromosome breakage, and that this capacity is somehow related to the presence of the C282Y HFE mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19146986", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 570, "text": "Compared to previous studies, we show that HFE mutation can possess the risk of AD in transferrin-, APOE- and APP-normal patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27081498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18316026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26501199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Hereditary hemochromatosis is caused by mutations in the hereditary hemochromatosis protein (HFE), transferrin-receptor 2 (TfR2), hemojuvelin, hepcidin, or ferroportin genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20177050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Genotyping of hemochromatosis-associated mutations in the HFE gene by PCR-RFLP and a novel reverse hybridization method.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11939483", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 330, "text": "Hereditary hemochromatosis, a common condition caused by HFE gene mutations, can lead to excess iron storage and disease but clinical penetrance of HFE gene mutations is low and many people with elevated iron stores lack HFE mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23512844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The three main mutations in gene HFE (C282Y, H63D, S65C) are the cause of development of 97% of cases of inherent hemochromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31529915", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. He", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26501199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Genetic iron overload, or hemochromatosis, can be caused by mutations in HFE, hemojuvelin, and hepcidin genes. He", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17255318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1). W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18316026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The mechanism of excessive iron storage in patients with hereditary hemochromatosis caused by mutations of the HFE gene seems to be a failure to up-regulate hepcidin in the face of increased body iron", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16154780", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1185, "text": "ith the common disease hereditary hemochromatosis, which is often caused by an HFE mutation, may have retinal iron overload predisposing to AMD. Preliminary data ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17065470", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 426, "text": "oxylase. New speculations have appeared on the possible relation of this role of iron and the occurrence of mutation of the recently discovered gene of the hereditary hemochromatosis HFE, which may cause the iron overloading of the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11191743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least five different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Neverth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28335084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Recent studies have shown that hereditary hemochromatosis (HH) is likely to be caused by homozygosity for a Cys282Tyr mutation in the HFE gene located 4.5 Mb telomeric to HLA-A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9358014", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 618, "text": "The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21175851", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 372, "text": "There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28406842", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 405, "text": "Less common non-HFE-related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12091366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Most types of genetic hemochromatosis are due to mutations in the HFE gene, although similar iron overload and organ damage can also result from mutations in genes other than HFE in rare types of hemochromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19907151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Mutations in HFE are the most common cause of hereditary hemochromatosis (HH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24904118", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1447, "text": "Furthermore, these results suggest that natural genetic variation in the human ortholog TMPRSS6 might modify the clinical penetrance of HFE-associated hereditary hemochromatosis, raising the possibility that pharmacologic inhibition of TMPRSS6 could attenuate iron loading in this disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21355094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The hereditary hemochromatosis protein HFE promotes the expression of hepcidin, a circulating hormone produced by the liver that inhibits dietary iron absorption and macrophage iron release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21355094", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 618, "text": "Mutations in the Hfe gene are associated with the iron overload disease, hemochromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15546588", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 455, "text": "It is known that about 85% of patients with inherent hemochromatosis are either homo-zygotic agents of mutation C282Y or carry compound-heterozygote C282Y/H63D. Therefore, the molecular genetic study intended for detection of these three mutations in gene HFE takes important place in diagnostic of inherent hemochromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31529915", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "[The comparison of three molecular genetic techniques for identifying major mutations in gene HFE related to development of inherent hemochromatosis.]", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31529915", "endSection": "title" }, { "offsetInBeginSection": 373, "offsetInEndSection": 455, "text": "The most common type of hereditary hemochromatosis is caused by HFE gene mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28406842", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 492, "text": "HFE participates in the regulation of iron metabolism, its mutations are primary cause of hereditary hemochromatosis and appear to be more frequent in neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18325820", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 498, "text": "Genetic hemochromatosis now corresponds to six diseases, namely classical hemochromatosis HFE 1; juvenile hemochromatosis HFE 2 due to mutations in an unidentified gene on chromosome 1; hemochromatosis HFE 3 due to mutations in the transferrin receptor 2 (TfR2); hemochromatosis HFE 4 caused by a mutation in the H subunit of ferritin; and hemochromatosis HFE 6 whose gene is hepcidine (HAMP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15506716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Mutations in HFE causing hemochromatosis are associated with primary hypertriglyceridemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19820015", "endSection": "title" }, { "offsetInBeginSection": 127, "offsetInEndSection": 947, "text": "factors. Elevated iron storage is associated with metabolic syndrome, diabetes, and obesity, and all of them are associated with HTG.OBJECTIVE: The aim of the study was to analyze whether HFE mutations causing hereditary hemochromatosis (HH) are associated with primary HTG.DESIGN: Genetic predisposition to HH was analyzed in a case-control study.SETTING: The study was conducted at University Hospital Lipid Clinic.PARTICIPANTS: We studied two groups: 1) the HTG group, composed of 208 patients; and 2) the control group, composed of 215 normolipemic subjects and 161 familial hypercholesterolemia patients.INTERVENTION: Two HFE mutations (C282Y and H63D) were analyzed.MAIN OUTCOME MEASURE: We measured HH genetic predisposition difference between groups.RESULTS: HH genetic predisposition was 5.9 and 4.4 times highe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19820015", "endSection": "abstract" } ] }, { "body": "What is the reason for the abundance of operons in the genome of C. elegans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25015138", "http://www.ncbi.nlm.nih.gov/pubmed/16752214", "http://www.ncbi.nlm.nih.gov/pubmed/20805997", "http://www.ncbi.nlm.nih.gov/pubmed/25525214", "http://www.ncbi.nlm.nih.gov/pubmed/23175478", "http://www.ncbi.nlm.nih.gov/pubmed/17712020", "http://www.ncbi.nlm.nih.gov/pubmed/18218978", "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "http://www.ncbi.nlm.nih.gov/pubmed/27124504", "http://www.ncbi.nlm.nih.gov/pubmed/9781873", "http://www.ncbi.nlm.nih.gov/pubmed/18050426" ], "ideal_answer": [ "Our data shows that transcription proceeds in some ways as if operons were composed of multiple adjacent single genes. Recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of machinery during recovery from growth arrested states.", "Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans . A recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states . Our data suggest operons and \"spliced leader\" trans-splicing predate the radiation of the nematode phylum .", "Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans, and a recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states. The operons contain primarily genes required for rapid growth, including genes whose products are needed for mitochondrial function and the basic machinery of gene expression. Recent evidence suggests that RNA polymerase is poised at the promoters of growth genes, and operons allow more efficient recovery from growth-arrested states, resulting in reduction in the need for this cache of inactive RNA polymerase.", "Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans. A recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states. C. elegans operons contain a much higher proportion of genes with multiple transcript isoforms than non-operonic genes do.", "Our data shows that transcription proceeds in some ways as if operons were composed of multiple adjacent single genes. Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans, and a recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states." ], "type": "summary", "id": "5fdb2e3ea43ad3127800000b", "snippets": [ { "offsetInBeginSection": 482, "offsetInEndSection": 601, "text": "Our data shows that transcription proceeds in some ways as if operons were composed of multiple adjacent single genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27124504", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 591, "text": "Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans, and a recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25525214", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1632, "text": "Our data suggest that operons and \"spliced leader\" (SL) trans-splicing predate the radiation of the nematode phylum, an inference which is supported by the phylogenetic profile of proteins known to be involved in nematode SL trans-splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "endSection": "abstract" }, { "offsetInBeginSection": 1438, "offsetInEndSection": 1655, "text": "These results provide support for the model that a necessity for increased transcriptional efficiency in the context of certain developmental processes could be a selective constraint for operon evolution in metazoans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25015138", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1436, "text": "However, analysis of gene-expression profiles identified conserved functions such as an enrichment of germline-expressed genes and higher expression levels of operonic genes during recovery from dauer arrest in both species", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25015138", "endSection": "abstract" }, { "offsetInBeginSection": 1818, "offsetInEndSection": 2231, "text": "The operons contain primarily genes required for rapid growth, including genes whose products are needed for mitochondrial function and the basic machinery of gene expression. Recent evidence suggests that RNA polymerase is poised at the promoters of growth genes, and operons allow more efficient recovery from growth-arrested states, resulting in reduction in the need for this cache of inactive RNA polymerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23175478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Caenorhabditis elegans operons contain a higher proportion of genes with multiple transcripts and use 3' splice sites differentially", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805997", "endSection": "title" }, { "offsetInBeginSection": 623, "offsetInEndSection": 746, "text": "C. elegans operons contain a much higher proportion of genes with multiple transcript isoforms than non-operonic genes do. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805997", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1261, "text": "Our analyses suggest that C. elegans operons enhance expression complexity by increasing the proportion of genes that express multiple transcript isoforms and maintain splicing efficiency by differential use of common 3' splice sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20805997", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1627, "text": "Based on a mathematic model of operon gains and losses and additional assumptions, we projected that the number of operons in C. elegans will continue to rise by 6%-18% in future evolution before reaching equilibrium between operon gains and losses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18218978", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1374, "text": "Our work suggests that hybrid operons are common in the C. elegans genome and that internal promoters influence not only gene organization and expression but also operon evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17712020", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 637, "text": "Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome. Further analyses suggest that this paucity of duplicated genes results from operon organization hindering specific types of gene duplication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16752214", "endSection": "abstract" }, { "offsetInBeginSection": 1371, "offsetInEndSection": 1720, "text": "The operons contain primarily genes whose products are needed for mitochondrial function and the basic machinery of gene expression: transcription, splicing and translation. Many operons contain genes whose products are known to function together. This presumably provides co-regulation of these proteins by producing a single RNA that encodes both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18050426", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 1106, "text": "genes with experimentally determined expression rates in the exponential growth phase, those of highest molar abundances are more deviant from the average gene codon frequencies and are more similar in codon frequencies to the average ribosomal protein gene. Independent of g", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9781873", "endSection": "abstract" } ] }, { "body": "Which chromosome contains the TLR7 locus in the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25650422", "http://www.ncbi.nlm.nih.gov/pubmed/25339659", "http://www.ncbi.nlm.nih.gov/pubmed/29374079", "http://www.ncbi.nlm.nih.gov/pubmed/27347137", "http://www.ncbi.nlm.nih.gov/pubmed/25541140", "http://www.ncbi.nlm.nih.gov/pubmed/21396113", "http://www.ncbi.nlm.nih.gov/pubmed/18682521", "http://www.ncbi.nlm.nih.gov/pubmed/30276444", "http://www.ncbi.nlm.nih.gov/pubmed/18521959", "http://www.ncbi.nlm.nih.gov/pubmed/16777955", "http://www.ncbi.nlm.nih.gov/pubmed/16709748", "http://www.ncbi.nlm.nih.gov/pubmed/18606711" ], "ideal_answer": [ "The TLR7 locus acts in vivo as a tumor suppressor gene and is located on chromosome X (X chromosome).", "The TLR7 locus acts on the X chromosome in humans and is located on chromosome 9 (XC7)", "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC) The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production.", "The X chromosome. TLR7 is encoded on X chromosome Xp22.", "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC) In this review we will discuss the role of the X chromosome encoded toll-like receptor 7 (TLR7) and interferon gamma (IFN\u03b3) in the development of autoimmunity.", "TLR7 (located on the X chromosome). Since the TLR7 gene is localized on the chromosome X, the allelic frequency of the Gln11Leu polymorphism was analyzed separately in males and females. TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC). The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production. Xp22 harbours the TLR7 and TLR8 genes.", "The X chromosome. TLR7 is encoded on X chromosome XP22.", "The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production . The major candidate gene for causation of the Yaa-associated autoimmune phenotypes has been TLR7 . The Toll like receptor 7 gene is encoded by a gene on the X chromosome gene, denoted TLR 7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells .", "The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production.", "The X chromosome. TLR7 is encoded by a gene on X chromosome Xp22.", "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse. X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR 7-mediated IFN-\u03b1 production of plasmacytoid dendritic cells from women." ], "exact_answer": [ "chromosomeX" ], "type": "factoid", "id": "5fdb4392a43ad3127800002a", "snippets": [ { "offsetInBeginSection": 479, "offsetInEndSection": 628, "text": "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30276444", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 405, "text": "In this review we will discuss the role of the X chromosome encoded toll-like receptor 7 (TLR7) and interferon gamma (IFN\u03b3) in the development of autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25541140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-\u03b1 production of plasmacytoid dendritic cells from women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25339659", "endSection": "title" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1639, "text": "Together, these results indicate that female sex hormones, estrogens, and X chromosome complement independently contribute to the enhanced TLR7-mediated IFN-\u03b1 response of pDCs in women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25339659", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 132, "text": "The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21396113", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 769, "text": "Although the translocated X chromosome segment in Yaa may contain as many as 16 genes, the major candidate gene for causation of the Yaa-associated autoimmune phenotypes has been TLR7. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18521959", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 213, "text": "Transcription profiling of yaa-bearing B cells revealed the overexpression of a cluster of X-linked genes that included Tlr7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16777955", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 320, "text": "By genome scanning, evidence of linkage between chromosome Xp22 and asthma and related atopic disorders has previously been obtained. Xp22 harbours the TLR7 and TLR8 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18682521", "endSection": "abstract" }, { "offsetInBeginSection": 1044, "offsetInEndSection": 1195, "text": "Since the TLR7 gene is localized on the chromosome X, the allelic frequency of the Gln11Leu polymorphism was analyzed separately in males and females. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27347137", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1218, "text": "TLR7 (located on the X chromosome)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25650422", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 818, "text": "Analysis of C57BL/6 mice congenic for the Nba2 (NZB autoimmunity 2) locus (B6.Nba2) bearing the Yaa mutation revealed that introduction of the Tlr7 null mutation on the X chromosome significantly reduced serum levels of IgG autoantibodies against DNA and ribonucleoproteins, as well as the incidence of lupus nephritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606711", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 768, "text": "Although the translocated X chromosome segment in Yaa may contain as many as 16 genes, the major candidate gene for causation of the Yaa-associated autoimmune phenotypes has been TLR7.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18521959", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 607, "text": "TLR7 is encoded by an X chromosome locus, and we examined here whether the TLR7 gene evades silencing by X chromosome inactivation in immune cells from women and Klinefelter syndrome males.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374079", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 858, "text": "Single-cell analyses of TLR7 allelic expression demonstrated that substantial fractions of primary B lymphocytes, monocytes, and plasmacytoid dendritic cells not only in women but also in Klinefelter syndrome males express TLR7 on both X chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374079", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1535, "text": "TLR7 escape from X inactivation endows the B cell compartment with added responsiveness to TLR7 ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29374079", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 364, "text": "Recently, the Yaa mutation was identified to be a translocation from the telomeric end of the X chromosome (containing the gene encoding TLR7) onto the Y chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18606711", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 665, "text": "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC), monocytes/macrophages, and B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30276444", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 393, "text": "Here, we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus are intrinsically biased toward nucleolar antigens because of increased expression of TLR7, a single-stranded RNA-binding innate immune receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16709748", "endSection": "abstract" }, { "offsetInBeginSection": 394, "offsetInEndSection": 498, "text": "The TLR7 gene is duplicated in Yaa mice because of a 4-Megabase expansion of the pseudoautosomal region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16709748", "endSection": "abstract" } ] }, { "body": "What is marked by DNaseI hypersensitive sites?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16963707", "http://www.ncbi.nlm.nih.gov/pubmed/6310495", "http://www.ncbi.nlm.nih.gov/pubmed/16857058", "http://www.ncbi.nlm.nih.gov/pubmed/10828050", "http://www.ncbi.nlm.nih.gov/pubmed/15070753", "http://www.ncbi.nlm.nih.gov/pubmed/11409913", "http://www.ncbi.nlm.nih.gov/pubmed/3004939", "http://www.ncbi.nlm.nih.gov/pubmed/17389645", "http://www.ncbi.nlm.nih.gov/pubmed/11567985", "http://www.ncbi.nlm.nih.gov/pubmed/21685456", "http://www.ncbi.nlm.nih.gov/pubmed/19728890", "http://www.ncbi.nlm.nih.gov/pubmed/19488879", "http://www.ncbi.nlm.nih.gov/pubmed/11231273", "http://www.ncbi.nlm.nih.gov/pubmed/22761590", "http://www.ncbi.nlm.nih.gov/pubmed/18283123", "http://www.ncbi.nlm.nih.gov/pubmed/18726358" ], "ideal_answer": [ "Hypersensitive sites are chromosomal regions up to 2kb distant to known genomic regulatory regions and 5 kb from known regulatory regions.", "Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements.", "DNaseI hypersensitive sites correspond to regions of the genome that have recently been isolated as well as specific genomic regulatory regions.", "DNaseI hypersensitive sites are chromosomal regions up to 2kb distant to known genomic regulatory regions and 5 kb from known regulatory regions.", "DNAaseI hypersensitive sites consist of covalent domains that are hypersensitive to DNA polymerase I and are generally found in genomic regulatory regions where transcription starts and stops at these regions.", "Mapping DNaseI hypersensitive sites is commonly used to identify regulatory regions in the genome.", "In genetics, DNase I hypersensitive sites (DHSs) are regions of chromatin that are sensitive to cleavage by the DNase I enzyme. In these specific regions of the genome, chromatin has lost its condensed structure, exposing the DNA and making it accessible.", "Yes, DNaseI hypersensitive sites have been shown to be markers for all types of active cis-acting regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions.", "DNA hypomethylation and the presence of DNaseI hypersensitive sites correlate with transcriptional activity of P1.1. Mapping sites within the genome that are hypersensitive to digestion withDNaseI is an important method for identifying DNA elements that regulate transcription.", "Mapping sites within the genome that are hypersensitive to digestion with DNaseI is an important method for identifying DNA elements that regulate transcription . The identification of cis-regulatory elements is central to understanding gene transcription . Of two promoter-like duplications in each spacer, only the most upstream copy is associated with hypersensitivity to DNAaseI .", "DNaseI hypersensitive sites correspond to regions along genomic regulatory regions where transcription starts and stops.", "The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements in regions of open chromatin." ], "exact_answer": [ "sites of transcriptional regulation", "gene regulatory sites", "transcriptional regulation binding sites", "cis-regulatory elements" ], "type": "factoid", "id": "5fdb2e23a43ad3127800000a", "snippets": [ { "offsetInBeginSection": 175, "offsetInEndSection": 525, "text": "In the present study, the binding of HMG proteins (HMG1/2 and HMG14/17) to the core DNA sequence of DNaseI hypersensitive site 2 (HS2core DNA sequence, -10681-10970 bp) in the locus control region (LCR) of the human beta-like globin gene cluster has been examined by using both thein vitro nucleosome reconstitution and the gel mobility shift assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18726358", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 616, "text": "The LCR is composed of a series of 5 DNaseI hypersensitive sites (5'HSs) that form in the nucleus of erythroid precursors. These HSs are conserved among mammals, bind transcription factors that also bind to other parts of the locus, and compose the functional components of the LCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11567985", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 927, "text": "Both DNA hypomethylation and the presence of DNaseI hypersensitive sites correlate with transcriptional activity of P1.1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11231273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Mapping sites within the genome that are hypersensitive to digestion with DNaseI is an important method for identifying DNA elements that regulate transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17389645", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 701, "text": "Of two promoter-like duplications in each spacer, only the most upstream copy is associated with hypersensitivity to DNAaseI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6310495", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 362, "text": "The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10828050", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 379, "text": "ocal alteration in chromatin structure in vivo, detectable through hypersensitivity to DNaseI and other nucleases, is the sine qua non of a diverse cast of transcriptional regulatory elements including enhancers, promoters, insulators, and locus control regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15070753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963707", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 340, "text": "Here, we characterize the evolutionary and functional characteristics of TE-derived human genome regulatory sequences uncovered by the high throughput mapping of DNaseI-hypersensitive (HS) sites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16857058", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 110, "text": "Mapping DNaseI hypersensitive sites is commonly used to identify regulatory regions in the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728890", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 443, "text": " regions of open chromatin [DNaseI hypersensitivity (DHS)]", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963707", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "BACKGROUND: Mapping DNaseI hypersensitive sites is commonly used to identify regulatory regions in the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728890", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 447, "text": "gions of extreme chromatin accessibility to DNaseI, commonly known as DNaseI hypersensitive sites, have been repeatedly shown to be markers for all types of active cis-acting regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions. However", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19488879", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 519, "text": "ng a high-throughput approach, we discovered DNaseI hypersensitive sites and potential regulatory elements along a 160-kb region of the genome that includes GDF3, Dppa3, and Nanog. We a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18283123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "To assess possible alterations of c-myc transcriptional control in murine B-cell tumors, we have investigated the pattern of DNaseI hypersensitive sites in the gene's putative regulatory region and within the gene in a variety of genomic contexts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3004939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "A number of DNaseI-hypersensitive (DH) sites have been mapped within a regulatory region situated upstream of the human apolipoprotein B (apoB) promoter (-5262 to -899) that is required for high level expression of human apoB transgenes in the livers of mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11409913", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 439, "text": "Regions of extreme chromatin accessibility to DNaseI, commonly known as DNaseI hypersensitive sites, have been repeatedly shown to be markers for all types of active cis-acting regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19488879", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 224, "text": "Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963707", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 712, "text": "Using ADHM we identified all previously recognized hematopoietic regulatory elements across 200 kb of the mouse T-cell acute", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963707", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 863, "text": "lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel elements within the locus, which show transcriptional regulatory activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963707", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The identification of cis-regulatory elements is central to understanding gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16963707", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 378, "text": "Focal alteration in chromatin structure in vivo, detectable through hypersensitivity to DNaseI and other nucleases, is the sine qua non of a diverse cast of transcriptional regulatory elements including enhancers, promoters, insulators, and locus control regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15070753", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 701, "text": "To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22761590", "endSection": "abstract" } ] }, { "body": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21262819", "http://www.ncbi.nlm.nih.gov/pubmed/18662993", "http://www.ncbi.nlm.nih.gov/pubmed/19053175", "http://www.ncbi.nlm.nih.gov/pubmed/19954516", "http://www.ncbi.nlm.nih.gov/pubmed/28765367", "http://www.ncbi.nlm.nih.gov/pubmed/30008320" ], "ideal_answer": [ "Yes. The polycomb group proteins (PcG) mediate the formation of chromatin loops by facilitating co-localization of heterochromatin loops.", "Polycomb action at a distance can be organized by local chromatin topology.", "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb response element (PRE) and a distal promoter Polycomb action at a distance can be organized by local chromatin topology", "Yes. The polycomb group proteins (PcG) mediate the formation of chromatin loops.", "Yes, polycomb group proteins (PcG) play a critical role in the formation of chromatin loops.", "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb response element (PRE) and a distal promoter Polycomb action at a distance can be organized by local chromatin topology Polycomb repressive complex 2 is recruited through the interaction of CTCF", "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb Response element (Pre) and a distal promoter Polycomb action at a distance can be organized by local chromatin topology Polycomb repressive complex 2 is recruited through the interaction of CTCF.", "Yes, the polycomb group proteins (PcG) play a critical role in the formation and/or maintenance of chromatin loops.", "Yes. Chromatin-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of exons of genes, such as PcG. The polycomb group proteins (PcG) mediate the formation of chromatin loops by binding to nuclear-insoluble structures at late-M-to-early-G1 on histone H3 lysine 27. Depending on what residue is mutated and the degree of transcription, polycomb loop formation is linked to either transcriptionally active or silent chromatin." ], "exact_answer": "yes", "type": "yesno", "id": "5fdb4290a43ad31278000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21262819", "endSection": "title" }, { "offsetInBeginSection": 462, "offsetInEndSection": 635, "text": "the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb response element (PRE) and a distal promoter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21262819", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1061, "text": "Polycomb action at a distance can be organized by local chromatin topology", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21262819", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 500, "text": "Polycomb repressive complex 2 is recruited through the interaction of CTCF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18662993", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1318, "text": "CTCF governs gene expression by orchestrating chromatin loop structures and by serving as a DNA-binding protein scaffold to recruit and bind polycomb repressive complexes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18662993", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1096, "text": "The chromatin loops completely dissolve, accompanied by loss of PcG proteins and H3K27me3 marks, when Tera-2 cells receive differentiation signals which induce a approximately 60-fold increase in GATA-4 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19053175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Polycomb-mediated chromatin loops revealed by a subkilobase-resolution chromatin interaction map.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28765367", "endSection": "title" }, { "offsetInBeginSection": 192, "offsetInEndSection": 472, "text": "es or \"anchors\" are associated with CTCF protein in mammals, loop anchors in Drosophila were found most often in association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of polycomb repressive complex 1 (PRC1). Loops were frequently located within domains of PcG", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28765367", "endSection": "abstract" }, { "offsetInBeginSection": 1824, "offsetInEndSection": 1998, "text": "We also provide novel insight that PcG-occupied and H3K27me3-enriched regions can form chromatin loops and physically interact in cis around a single gene in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19053175", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 846, "text": "Repressive loops within polycomb domains are formed after the midblastula transition between polycomb response elements by the action of GAGA factor and polycomb proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30008320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "PcG proteins, DNA methylation, and gene repression by chromatin looping.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19053175", "endSection": "title" }, { "offsetInBeginSection": 421, "offsetInEndSection": 493, "text": "Loops were frequently located within domains of PcG-repressed chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28765367", "endSection": "abstract" }, { "offsetInBeginSection": 1910, "offsetInEndSection": 2090, "text": "iation to proliferation control. Our results revealed a chromatin looping mechanism of long-range control and argue against models involving homogeneous spreading of PcG silencers ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19954516", "endSection": "abstract" } ] }, { "body": "Which type of analysis does DeSeq2 perform?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33102519", "http://www.ncbi.nlm.nih.gov/pubmed/32368594", "http://www.ncbi.nlm.nih.gov/pubmed/30987214", "http://www.ncbi.nlm.nih.gov/pubmed/27280887", "http://www.ncbi.nlm.nih.gov/pubmed/27528462", "http://www.ncbi.nlm.nih.gov/pubmed/27748458", "http://www.ncbi.nlm.nih.gov/pubmed/32720149", "http://www.ncbi.nlm.nih.gov/pubmed/27695478", "http://www.ncbi.nlm.nih.gov/pubmed/27022159", "http://www.ncbi.nlm.nih.gov/pubmed/33072607", "http://www.ncbi.nlm.nih.gov/pubmed/25516281", "http://www.ncbi.nlm.nih.gov/pubmed/26919855", "http://www.ncbi.nlm.nih.gov/pubmed/26539333", "http://www.ncbi.nlm.nih.gov/pubmed/32609094", "http://www.ncbi.nlm.nih.gov/pubmed/30984248" ], "ideal_answer": [ "DeSeq2 is a software for differential gene expression analysis of RNA sequencing data.", "Both TMM and DESeq2 are widely used for differential gene expression analysis.", "DeSeq2 performed differential gene expression analysis of paired-end tag sequencing data.", "DeSeq2 supports differential gene expression analysis by combining multiple sources of evidence.", "DeSeq2 enables differential gene expression analysis of multiple cellular origins.", "DesSeq2 is widely used for differential gene expression analysis.", "DESeq2 is a method for differential analysis of count data. It is used for the calculation of fold change and dispersion of RNA-seq data." ], "exact_answer": [ "differential analysis of RNASeq data" ], "type": "factoid", "id": "5fdb41b6a43ad3127800001d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516281", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 403, "text": " DESeq2, a method for differential analysis of count dat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516281", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1087, "text": "t is based on DESeq2 and edgeR and is composed of an R package and two R script templates (for DESeq2 and edgeR respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27280887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "SARTools: A DESeq2- and EdgeR-Based R Pipeline for Comprehensive Differential Analysis of RNA-Seq Data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27280887", "endSection": "title" }, { "offsetInBeginSection": 529, "offsetInEndSection": 608, "text": "Both TMM and DESeq2 are widely used for differential gene expression analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27695478", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1219, "text": "A Venn diagram is a useful method to compare the differentially expressed genes across various comparisons and steps to generate the Venn diagram from DESeq2 results are provided.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32720149", "endSection": "abstract" }, { "offsetInBeginSection": 2483, "offsetInEndSection": 2727, "text": "When triplicates or more are available, GFOLD is a sharp tool for identifying high confidence differentially expressed genes for targeted qPCR validation; for downstream systems level analysis, combined results from DESeq2 and edgeR are useful.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26539333", "endSection": "abstract" }, { "offsetInBeginSection": 1752, "offsetInEndSection": 1976, "text": "At a replicate size of six, we found DESeq2 and edgeR to be reasonable methods for calling differentially expressed genes at systems level analysis, as their PPV and sensitivity trade-off were superior to the other methods'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26539333", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1664, "text": "The whole process consists of three main steps (1) Data Analysis: that allows a preliminary analysis for quality control based on the data distribution per sample, using different types of graphs; (2) Differential expression: performs the differential expression analysis with or without batch effect error awareness, using the bioconductor packages, NOISeq, limma-Voom, DESeq2 and edgeR, and generate reports for each method; (3) Result integration: the obtained results the integrated results are reported using different graphical outputs such as correlograms, heatmaps, Venn diagrams and text lists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30984248", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 617, "text": "thod, we identified 138 differentially expressed genes (DEGs) between Bf and Sol. Using DEGseq met", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27748458", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 581, "text": "w data were analyzed for differential gene expression using a negative binomial generalized linear model in the DeSeq2 software package. We u", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32368594", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 528, "text": "DEseq2 tool was used to obtain differentially-expressed miRNAs. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32609094", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 557, "text": "Producing a coherent differential gene expression analysis from RNA-seq count data requires an understanding of how numerous sources of variation such as the replicate size, the hypothesized biological effect size, and the specific method for making differential expression calls interact.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26539333", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 521, "text": "We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25516281", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 607, "text": "Both TMM and DESeq2 are widely used for differential gene expression analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27695478", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 903, "text": "Differential analysis between two TMB groups was performed using \"DESeq2\" R package to identify differentially expressed genes (DEGs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33072607", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 728, "text": "High-quality reads are mapped using Bowtie2 and differentially expressed genes across different groups were estimated using the DEseq2 R-Bioconductor package.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32720149", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 852, "text": "DESeq2's generalized linear model was applied with two hypothesis testing approaches to identify differentially-expressed (DE) genes, both between pairs of age groups and across mice of all ages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33102519", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1726, "text": "geR robust. These methods attempt to overcome the inherently noisy behavior of low-count transcripts by either shrinkage or differential weighting of observations, respectively.RESULTS: Both DE methods seemed to properly control family-wise type 1 error on low-count transcripts, whereas edgeR robust showed greater power and DESeq2 showed greater pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26919855", "endSection": "abstract" }, { "offsetInBeginSection": 1191, "offsetInEndSection": 1346, "text": "Gene Ontology (GO) enrichment analysis revealed no skewness in significant GO terms identified among differentially expressed genes by edgeR versus DESeq2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30987214", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 948, "text": "analysis of covariance,t-tests, linear regression, differential abundance (DESeq2), and principal coordinates analysis (PCoA)) and normalization (rarefaction, DESeq2, and proportion) tools for the comparative analysis of taxonomic abundance, species richness and species diversity for projects of various types (e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27022159", "endSection": "abstract" } ] }, { "body": "What is the function of a protein degron?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26214256", "http://www.ncbi.nlm.nih.gov/pubmed/27820801", "http://www.ncbi.nlm.nih.gov/pubmed/17962019", "http://www.ncbi.nlm.nih.gov/pubmed/29777695", "http://www.ncbi.nlm.nih.gov/pubmed/10545111", "http://www.ncbi.nlm.nih.gov/pubmed/28292960", "http://www.ncbi.nlm.nih.gov/pubmed/9806417", "http://www.ncbi.nlm.nih.gov/pubmed/19401679", "http://www.ncbi.nlm.nih.gov/pubmed/28680098", "http://www.ncbi.nlm.nih.gov/pubmed/26435348", "http://www.ncbi.nlm.nih.gov/pubmed/25653450" ], "ideal_answer": [ "Protein degrons are part of the DNA damage response triggered by dysfunctional transcription factors. Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine residues that targets them to the proteolytic machinery. Disruption of one degron by a RNA-binding protein causes it to become ubiquitinated, dimerizes and translocates to the nucleus.", "A protein degron is a protein that is attached to the N-terminus of a protein of interest. The N-degron then targets itself and the attached protein for rapid proteasomal degradation.", "A N-degron can be attached to the N-terminus of a protein of interest. Upon expression of a site-specific protease, the dormant N-degron becomes deprotected. The N-degron then targets itself and the attached protein for rapid proteasomal degradation through the N-end rule pathway.", "A protein degron is a protein that is attached to the N-terminus of a protein of interest. The N-degron then targets itself and the attached protein for rapid proteasomal degradation through a N-end rule pathway.", "The N-degron protein degradation strategy for investigating the function of essential genes We developed a dormant N-degron that can be attached to the N-terminus of a protein of interest. Upon expression of a site-specific protease, the dormant N-degron becomes deprotected.", "Protein degrons are artificial short peptides which specifically bind to defined functional domains, track, and inhibit a given target molecule with high affinity and specificity. They represent a remarkable alternative to antibodies in many applications.", "A protein degron is a protein that is attached to the N-terminus of a protein of interest. The N-degron then targets itself and the attached protein for rapid proteasomal degradation through a N-end rule pathway. The degradation pathway is a pathway in which proteins are fused to a degron that removes itself in an absence of drug, resulting in an untamable protein." ], "type": "summary", "id": "5eb9a7f60d431b5f7300000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "The N-degron protein degradation strategy for investigating the function of essential genes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9806417", "endSection": "title" }, { "offsetInBeginSection": 234, "offsetInEndSection": 542, "text": "We developed a dormant N-degron that can be attached to the N-terminus of a protein of interest. Upon expression of a site-specific protease, the dormant N-degron becomes deprotected. The N-degron then targets itself and the attached protein for rapid proteasomal degradation through the N-end rule pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19401679", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 313, "text": " We describe small molecule-assisted shutoff (SMASh), a technique in which proteins are fused to a degron that removes itself in the absence of drug, resulting in the production of an untagged protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26214256", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 162, "text": "The auxin-inducible degron harbors great potential for dynamic protein depletion in yeast", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28680098", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 496, "text": "We fused two degron components into a single molecule to create a fusion protein comprising ubiquitin and Rpn4-derived unstructured region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29777695", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 1070, "text": "Functioning as a protein degron, the cellular IAP leader dramatically shortened the life span of a long-lived viral IAP (Op-IAP3) when fused to its N terminus. The SfIAP degron contains mitogen-activated kinase (MAPK)-like regulatory sites, responsible for MAPK inhibitor-sensitive phosphorylation of SfIAP. Hyperphosphorylation correlated with increased SfIAP turnover independent of the E3 ubiquitin-ligase activity of the SfIAP RING, which also regulated IAP stability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653450", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 408, "text": "We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27820801", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 1039, "text": "The degron mediated protein degradation represents a rapidly tunable methodology to control protein abundance, which has broad application in therapeutics and cellular function control and monitoring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26435348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The N-end rule pathway is a ubiquitin-dependent proteolytic system, in which destabilizing N-terminal residues of short-lived proteins function as an essential determinant of an N-terminal degradation signal (N-degron).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17962019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28292960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "A 'distributed degron' allows regulated entry into the ER degradation pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10545111", "endSection": "title" } ] }, { "body": "Which computational methods are used for the definition of synteny?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22217600", "http://www.ncbi.nlm.nih.gov/pubmed/25137074", "http://www.ncbi.nlm.nih.gov/pubmed/19728289", "http://www.ncbi.nlm.nih.gov/pubmed/19549318", "http://www.ncbi.nlm.nih.gov/pubmed/28671949", "http://www.ncbi.nlm.nih.gov/pubmed/27594782", "http://www.ncbi.nlm.nih.gov/pubmed/18721485", "http://www.ncbi.nlm.nih.gov/pubmed/17343765", "http://www.ncbi.nlm.nih.gov/pubmed/18025683" ], "ideal_answer": [ "The computational methods which are used for the definition of synteny are:1) multisyn, 2) poff, 3) orthocluster, 4) phyldiag, 5) synblast, 6) cinteny, 7) domain team, 8)mcscanx and 9) run Orthoclusterdb and 10) view synteny.", "Computational methods used for the definition of synteny include multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainmanagement, domainweekly, domainScanx, run orthocluster, orthClusterdb and view synteny.", "Computational methods used for the definition of synteny include multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainmanagement, domainScanx, run orthoclustereddb, view synteny and others.", "The automated and fast detection of syntenic domain teams is implemented in the DomainTeam software. Here we present the SynBlast pipeline that is designed to construct and evaluate local synteny information. Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances. OrthoClusterDB is a new online platform for the identification and visualization of synteny blocks. OrthoClusterDB consists of two key web pages: Run OrthoCluster and View Synteny. MCScan is an algorithm able to scan multiple genomes or subgenomes in order to identify putative homologous chromosomal regions, and align these regions using genes as anchors. PoFF is an extension for the standalone tool Proteinortho, which enhances orthology detection by combining clustering, sequence similarity, and synteny. MultiSyn: A Webtool for Multiple Synteny Detection and Visualization of User's Sequence of Interest Compared to Public Plant Species.", "Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection. Here we present the SynBlast pipeline that is designed to construct and evaluate local synteny information. PoFF is an extension for the standalone tool Proteinortho, which enhances orthology detection by combining clustering, sequence similarity, and synteny.", "Computational methods used for the definition of synteny include multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainmanagement, electrophobicity, run orthoclustereddb, mcScan and view synteny.", "The computational methods that are used for the definition of synteny are: multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainteam, mcscanx and run orthoclustersdb." ], "exact_answer": [ [ "Domain Team" ], [ "Cinteny" ], [ "SynBlast" ], [ "OrthoCluster" ], [ "MCScanX" ], [ "PoFF" ], [ "MultiSyn" ], [ "PhylDiag" ], [ "Cyntenator" ] ], "type": "list", "id": "5fdb2f77a43ad31278000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Domain team: synteny of domains is a new approach in comparative genomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025683", "endSection": "title" }, { "offsetInBeginSection": 818, "offsetInEndSection": 971, "text": "The automated and fast detection of domain teams is implemented in the DomainTeam software. In this chapter, we describe the procedure to run DomainTeam.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025683", "endSection": "abstract" }, { "offsetInBeginSection": 1794, "offsetInEndSection": 1974, "text": "Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17343765", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 699, "text": "Here we present the SynBlast pipeline that is designed to construct and evaluate local synteny information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18721485", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 740, "text": "OrthoClusterDB is a new online platform for the identification and visualization of synteny blocks. OrthoClusterDB consists of two key web pages: Run OrthoCluster and View Synteny.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549318", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1633, "text": "For both Run OrthoCluster and View Synteny, identified synteny blocks can be browsed at the whole genome, chromosome, and individual gene level. OrthoClusterDB is freely accessible", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19549318", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 78, "text": "OrthoCluster for the detection of synteny blocks among multiple genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728289", "endSection": "title" }, { "offsetInBeginSection": 761, "offsetInEndSection": 968, "text": "OrthoClusterDB provides a Web interface for running OrthoCluster with user-defined datasets and parameters, as well as for browsing and downloading precomputed synteny blocks for different groups of genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "MCScanX: a toolkit for detection and evolutionary analysis of gene synteny and collinearity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22217600", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "MCScan is an algorithm able to scan multiple genomes or subgenomes in order to identify putative homologous chromosomal regions, and align these regions using genes as anchors. The MCScanX toolkit implements an adjusted MCScan algorithm for detection of synteny and collinearity that extends the original software by incorporating 14 utility programs for visualization of results and additional downstream analyses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22217600", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 490, "text": "Here we present PoFF, an extension for the standalone tool Proteinortho, which enhances orthology detection by combining clustering, sequence similarity, and synteny. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25137074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "MultiSyn: A Webtool for Multiple Synteny Detection and Visualization of User's Sequence of Interest Compared to Public Plant Species.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27594782", "endSection": "title" }, { "offsetInBeginSection": 676, "offsetInEndSection": 915, "text": " Here, we introduce a web application that determines and visualizes multiple synteny from two types of files, simplified browser extensible data and protein sequence file by MCScanX algorithm, which have been used in many synteny studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27594782", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 973, "text": "All these refinements are implemented in a new version of PhylDiag that has been benchmarked against i-ADHoRe 3.0 and Cyntenator, based on a realistic simulated evolution and true simulated conserved segments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28671949", "endSection": "abstract" } ] }, { "body": "Can ATAC-Seq be employed in single-cell mode?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30451828", "http://www.ncbi.nlm.nih.gov/pubmed/28138849", "http://www.ncbi.nlm.nih.gov/pubmed/32637041", "http://www.ncbi.nlm.nih.gov/pubmed/32029740", "http://www.ncbi.nlm.nih.gov/pubmed/32620137", "http://www.ncbi.nlm.nih.gov/pubmed/30559361", "http://www.ncbi.nlm.nih.gov/pubmed/26294014", "http://www.ncbi.nlm.nih.gov/pubmed/32029221", "http://www.ncbi.nlm.nih.gov/pubmed/30936163", "http://www.ncbi.nlm.nih.gov/pubmed/31594952", "http://www.ncbi.nlm.nih.gov/pubmed/31428792", "http://www.ncbi.nlm.nih.gov/pubmed/30580963", "http://www.ncbi.nlm.nih.gov/pubmed/26083756", "http://www.ncbi.nlm.nih.gov/pubmed/30335168", "http://www.ncbi.nlm.nih.gov/pubmed/29686426" ], "ideal_answer": [ "Single-cell ATAC-seq detects open chromatin in individual cells.", "When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells.", "Yes. When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells.", "Single-cell ATAC-seq: strength in numbers. When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells.", "Yes. The method can be also employed in single-cell mode, allowing the analysis of cell-based epigenetic changes only.", "Yes, ATAC-seq can be employed in single-cell mode.", "Yes, single-cell ATAC-seq can be used to detect genome-wide the binding sites of RNA binding proteins in individual cells.", "Yes. ATAC-seq can be used as a primary method for analyzing genome-wide open chromatin structure within single-cell populations." ], "exact_answer": "yes", "type": "yesno", "id": "5fe31319a43ad31278000046", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Single-cell ATAC-seq: strength in numbers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26294014", "endSection": "title" }, { "offsetInBeginSection": 86, "offsetInEndSection": 121, "text": "Assembly, and Single-Cell ATAC-Seq.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28138849", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30451828", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 474, "text": " Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30451828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Classifying cells with Scasat, a single-cell ATAC-seq analysis tool.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335168", "endSection": "title" }, { "offsetInBeginSection": 213, "offsetInEndSection": 465, "text": "When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029221", "endSection": "title" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1138, "text": "THODS: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq). W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Contiguity-Preserving Transposition Sequencing (CPT-Seq) for Genome-Wide Haplotyping, Assembly, and Single-Cell ATAC-Seq.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28138849", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "SCALE method for single-cell ATAC-seq analysis via latent feature extraction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31594952", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Single-cell ATAC-seq (scATAC-seq) profiles the chromatin\u00a0accessibility landscape at single cell level, thus revealing cell-to-cell variability in gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31594952", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 447, "text": "The recently developed low-input and single-cell regulome mapping technologies such as ATAC-seq and single-cell ATAC-seq (scATAC-seq) allow analyses of small-cell-number and single-cell samples, but their signals remain highly discrete or noisy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31428792", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 596, "text": "This paper presents Scasat (single-cell ATAC-seq analysis tool), a complete pipeline to process scATAC-seq data with simple steps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30335168", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 474, "text": "Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30451828", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 886, "text": "Single-cell ATAC-seq (scATAC-seq) technology has also been developed to study cell type-specific chromatin accessibility in tissue samples containing a heterogeneous cellular population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637041", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 459, "text": "Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29686426", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 301, "text": "Substantial advances of this work include the optimization of a single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq); a software suite,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30936163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "The accessible chromatin landscape of the murine hippocampus at single-cell resolution.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30936163", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30936163", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1743, "text": "We expect this review will provide a guideline for successful data generation and analysis methods using appropriate software tools and databases for the study of chromatin accessibility at single-cell resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscapes in single cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620137", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 266, "text": "Single-cell ATAC-seq data are sparse and noisy, and analyzing such data is challenging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620137", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 393, "text": "Here, we introduce a method for analyzing scATAC-seq data, called Single-Cell ATAC-seq analysis via Latent feature Extraction (SCALE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31594952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Single-cell ATAC-seq signal extraction and enhancement with SCATE.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620137", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Single-cell ATAC-seq detects open chromatin in individual cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26294014", "endSection": "abstract" }, { "offsetInBeginSection": 65, "offsetInEndSection": 203, "text": "Currently data are sparse, but combining information from many single cells can identify determinants of cell-to-cell chromatin variation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26294014", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1045, "text": "Predictions based on single-cell RNA-seq (scRNA-seq) can more accurately reconstruct bulk chromatin accessibility than using scATAC-seq.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31428792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Global prediction of chromatin accessibility using small-cell-number and single-cell RNA-seq.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31428792", "endSection": "title" }, { "offsetInBeginSection": 647, "offsetInEndSection": 849, "text": "Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26083756", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 256, "text": "However, very few studies have been performed at the single cell level (scATAC-seq) due to technical challenges.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30559361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Here, we present Perturb-ATAC, a method that combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by assay of transposase-accessible chromatin with sequencing (ATAC-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30580963", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 1014, "text": "Additionally, the same workflow can be used to aid de novo assembly (Adey et al., Genome Res 24(12):2041-2049, 2014), detect structural variants, and perform single cell ATAC-seq analysis (Cusanovich et al., Science 348(6237):910-914, 2015).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28138849", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 857, "text": "ChromA can analyze single cell ATAC-seq data, correcting many biases generated by the sparse sampling inherent in single cell technologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029740", "endSection": "abstract" }, { "offsetInBeginSection": 741, "offsetInEndSection": 1116, "text": " circuits. Existing chromatin profiling methods such as ATAC-seq and DNase-seq, applied to islets in bulk, produce aggregate profiles that mask important cellular and regulatory heterogeneity.METHODS: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "ATAC-seq has become a leading technology for probing the chromatin landscape of single and aggregated cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029740", "endSection": "abstract" } ] }, { "body": "How can B-cells transdifferentiate into macrophages?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28584084", "http://www.ncbi.nlm.nih.gov/pubmed/26286813", "http://www.ncbi.nlm.nih.gov/pubmed/22981865", "http://www.ncbi.nlm.nih.gov/pubmed/15163413", "http://www.ncbi.nlm.nih.gov/pubmed/25607658", "http://www.ncbi.nlm.nih.gov/pubmed/28111277", "http://www.ncbi.nlm.nih.gov/pubmed/24421386", "http://www.ncbi.nlm.nih.gov/pubmed/23545498", "http://www.ncbi.nlm.nih.gov/pubmed/21969581", "http://www.ncbi.nlm.nih.gov/pubmed/24336202", "http://www.ncbi.nlm.nih.gov/pubmed/22086955", "http://www.ncbi.nlm.nih.gov/pubmed/18472258", "http://www.ncbi.nlm.nih.gov/pubmed/22771961", "http://www.ncbi.nlm.nih.gov/pubmed/28356547" ], "ideal_answer": [ "Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis . Vascular endothelial growth factor modified macrophage transdifferentiates into endothelial-like cells and decrease foam cell formation . Human cancer cells can be induced by C/EBP\u03b1 to transdifferentiated into seemingly normal cells at high frequencies .", "Through the ectopic over-expression of the CCAAT/enhancer binding protein-\u03b1 (C/EBP\u03b1), which induces transdifferentiation of B cells into macrophages at high efficiencies.", "C/EBP\u03b2-expressing B cells produced granulocyte-macrophage progenitor progenitors when subjected to selective pressure to eliminate lymphoid cells . The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells . Tet2 helps CEBP\u03b1 rapidly derepress myeloid genes during conversion of pre-B cells .", "C/EBP\u03b2-expressing B cells produced granulocyte-macrophage progenitor (GMP)-like progenitors when subjected to selective pressure to eliminate lymphoid cells. Tet2 helps CEBP\u03b1 rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages.", "Human cancer cells can be induced by C/EBP\u03b1 to transdifferentiate into seemingly normal cells at high frequencies . This provides a proof of principle for a potential new therapeutic strategy for treating B cell malignancies . Inflammatory macrophages\u00a0transdifferentiate\u00a0into myofibroblasts\u00a0during renal fibrosis ." ], "type": "summary", "id": "5fdb43c2a43ad3127800002c", "snippets": [ { "offsetInBeginSection": 1157, "offsetInEndSection": 1261, "text": "The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26286813", "endSection": "abstract" }, { "offsetInBeginSection": 471, "offsetInEndSection": 684, "text": "By comparing B cells with macrophage-like cells trans-differentiated by ectopic expression of C/EBP\u03b2, iChIP-SILAC detected B cell-specific interaction of a nuclear protein, Thy28/Thyn1, with the Pax5 1A promoter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25607658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111277", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 307, "text": "Conversion of B cells to macrophages was readily induced by the ectopic expression of any C/EBP, and enhanced by endogenous C/EBP\u03b1 and \u03b2 activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111277", "endSection": "abstract" }, { "offsetInBeginSection": 497, "offsetInEndSection": 653, "text": "C/EBP\u03b2-expressing B cells produced granulocyte-macrophage progenitor (GMP)-like progenitors when subjected to selective pressure to eliminate lymphoid cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28111277", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 790, "text": "Through the investigation of reprogramming mechanisms, we recently revealed that over-expression of constitutive active Smad3 boosted not only iPSC generation, but also 3 other master TF-mediated conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28356547", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 1029, "text": "Focusing on B-cell and macrophage development, we defined a qualitative dynamical model recapitulating cytokine-induced differentiation of common progenitors, the effect of various reported gene knockdowns, and the reprogramming of pre-B cells into macrophages induced by the ectopic expression of specific transcription factors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28584084", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "C/EBP\u03b1 poises B cells for rapid reprogramming into induced pluripotent stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336202", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "CCAAT/enhancer binding protein-\u03b1 (C/EBP\u03b1) induces transdifferentiation of B cells into macrophages at high efficiencies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336202", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 272, "text": "An ideal system to study the role of Tet2 in myelopoeisis is CEBP\u03b1-induced transdifferentiation of pre-B cells into macrophages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981865", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1033, "text": "Our observations indicate that Tet2 helps CEBP\u03b1 rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22981865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "CCAAT/enhancer binding protein alpha (C/EBP(alpha))-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21969581", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor CCAAT/enhancer binding protein \u03b1 at very high frequencies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21969581", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 570, "text": "Forced C/EBPalpha expression furthermore induces direct transdifferentiation of immature thymocytes or B cells into macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18472258", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 1156, "text": "Our experiments show that human cancer cells can be induced by C/EBP\u03b1 to transdifferentiate into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy for treating B cell malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Earlier work demonstrated that the transcription factor C/EBP\u03b1 can convert immature and mature murine B lineage cells into functional macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545498", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 358, "text": "esting >20 human lymphoma and leukemia B cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBP\u03b1 is expressed at sufficiently high levels. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "CCAAT/enhancer binding protein-\u03b1 (C/EBP\u03b1) induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem (iPS) cells when co-expressed with the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and Myc (hereafter called OSKM). Howev", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336202", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 572, "text": "ced C/EBPalpha expression furthermore induces direct transdifferentiation of immature thymocytes or B cells into macrophages. N", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18472258", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 437, "text": " we report that enforced expression of C/EBPalpha and C/EBPbeta in differentiated B cells leads to their rapid and efficient reprogramming into macrophages. C/EB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15163413", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 567, "text": "A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/EBP\u03b1ER, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545498", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 474, "text": "We here investigated the acquisition of DNA methylation changes during C/EBP\u03b1-induced pre-B cell to macrophage transdifferentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086955", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 1038, "text": "We also demonstrated that C/EBP\u03b1 and RNA Pol II are associated with the methylated promoters of macrophage-specific genes in reprogrammed macrophages without inducing methylation changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086955", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 356, "text": "Testing >20 human lymphoma and leukemia B cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBP\u03b1 is expressed at sufficiently high levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Our earlier work has shown that pre-B cells can be converted into macrophage-like cells by overexpression of the transcription factor C/EBP\u03b1 or C/EBP\u03b2 with high efficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22771961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "CCAAT/enhancer binding protein-\u03b1 (C/EBP\u03b1) induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem (iPS) cells when co-expressed with the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and Myc (hereafter called OSKM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "C/EBP\u03b1 induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23545498", "endSection": "title" }, { "offsetInBeginSection": 117, "offsetInEndSection": 376, "text": "C/EBPa-induced pre-B cell-to-macrophage transdifferentiation provides an excellent model to investigate the contribution of miRNAs to hematopoietic cell identity, especially because the two cell types involved fall into separate lymphoid and myeloid branches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24421386", "endSection": "abstract" } ] }, { "body": "What is the function of the chromHMM software?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31695717", "http://www.ncbi.nlm.nih.gov/pubmed/26865847", "http://www.ncbi.nlm.nih.gov/pubmed/25708947", "http://www.ncbi.nlm.nih.gov/pubmed/25810430", "http://www.ncbi.nlm.nih.gov/pubmed/29120462", "http://www.ncbi.nlm.nih.gov/pubmed/30309205", "http://www.ncbi.nlm.nih.gov/pubmed/27706663" ], "ideal_answer": [ "ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark . It uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment . Chromatin states are learned, annotations are produced, and enrichments are computed within 1 d .", "The ChromHMM software is a tool for learning chromatin-state signatures. It allows you to learn chromatin states, and then use that knowledge to make an annotated chromatin state for each cell type.", "ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark. ChromHMM uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment. ChromHMM helps to annotate the noncoding genome using epigenomic information across one or multiple cell types. It combines multiple genome-wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer a complete annotation for each cell type", "ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark. It uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment.", "The ChromHMM software is a tool for learning chromatin-state signatures. It allows you to learn chromatin states, and then use that knowledge to make an annotated chromatin state for a cell type." ], "type": "summary", "id": "5fdb43d4a43ad3127800002d", "snippets": [ { "offsetInBeginSection": 267, "offsetInEndSection": 497, "text": "Here, we publish a frequency profile of the three ChromHMM promoter states, at 200-bp intervals, with particular reference to the existence of sequence patterns of promoter elements, GC-richness, and transcription starting sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865847", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 660, "text": "ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark. ChromHMM uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29120462", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 811, "text": "ChromHMM provides an automated enrichment analysis of the resulting annotations to facilitate the functional interpretations of each chromatin state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29120462", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 1087, "text": "ChromHMM is distinguished by its modeling emphasis on combinations of marks, its tight integration with downstream functional enrichment analyses, its speed, and its ease of use. Chromatin states are learned, annotations are produced, and enrichments are computed within 1 d.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29120462", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 343, "text": "ChromHMM helps to annotate the noncoding genome using epigenomic information across one or multiple cell types. It combines multiple genome-wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer a complete annotation for each cell type", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29120462", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 896, "text": "Our aim was to identify the possible relationship between DNA sequences and the newly built chromatin states based on the integrated ChromHMM datasets of different cells and tissue types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30309205", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 496, "text": "Here, we publish a frequency profile of the three ChromHMM promoter states, at 200-bp intervals, with particular reference to the existence of sequence patterns of promoter elements, GC-richness, and transcription starting sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Building the Frequency Profile of the Core Promoter Element Patterns in the Three ChromHMM Promoter States at 200bp Intervals: A Statistical Perspective.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26865847", "endSection": "title" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1485, "text": "Based on the ChromHMM algorithm, the genome was divided into 620,122 fragments, which were classified into 24 states according to the combination of epigenetic marks and enriched-feature regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31695717", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 708, "text": "The nucleotide frequency profiles of nine chromatin annotations with the units of 200 bp were analyzed and integrative Markov chains were built to detect the Markov properties of the DNA sequences in some of the active chromatin states of different ChromHMM regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30309205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "We analyzed the publicly available ChromHMM BED files of the ENCODE project and tested the Markov properties of the different chromatin states in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27706663", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1630, "text": "In addition, we comprehensively compare our method to ChromHMM on three real datasets and show that our method estimates more chromatin states than ChromHMM for those datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810430", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1180, "text": "RESULTS: In this paper, we propose a linear time algorithm for calculating a set of non-overlapping regions that maximizes the sum of similarities between the vector of focal epigenetic states and the vectors of raw epigenetic states at DNA positions in the set of regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25708947", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 356, "text": "Nucleotide frequency profiles of regional chromatin segmentations were analyzed, and Markov chains were built to detect Markov properties in the chromatin states of different ChromHMM regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27706663", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 828, "text": "RESULTS: In this study, we propose a method to estimate the chromatin states indicated by genome-wide chromatin marks identified by NGS technologies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810430", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1075, "text": "The proposed method automatically estimates the number of chromatin states and characterize each state on the basis of a hidden Markov model (HMM) in combination with a recently proposed model selection technique, factorized information criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25810430", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1087, "text": "Chromatin states are learned, annotations are produced, and enrichments are computed within 1 d.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29120462", "endSection": "abstract" } ] }, { "body": "What is FeatureCounts used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "http://www.ncbi.nlm.nih.gov/pubmed/28096075", "http://www.ncbi.nlm.nih.gov/pubmed/28915787", "http://www.ncbi.nlm.nih.gov/pubmed/30379987" ], "ideal_answer": [ "featureCounts is a general purpose program for assigning sequence reads to genomic features. It is a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments.", "featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments", "featureCounts can be used to quantify reads generated from either RNA or DNA sequencing technologies in terms of any type of genomic feature. It implements chromosome hashing, feature blocking and other strategies to assign reads to features with high efficiency.", "Featurecounts is a system that uses a novel Bayesian approach to calculate informative metrics at each depth required to inform a broad range of functional and evolutionary studies. The database is optimized to support fast interactive performance with the RNA-Seq platform.", "featureCounts: an efficient general purpose program for assigning sequence reads to genomic features.", "We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments." ], "exact_answer": [ "assigning sequence reads to genomic features" ], "type": "factoid", "id": "5fdb41c5a43ad3127800001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "featureCounts: an efficient general purpose program for assigning sequence reads to genomic features.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "title" }, { "offsetInBeginSection": 524, "offsetInEndSection": 670, "text": "We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "abstract" }, { "offsetInBeginSection": 701, "offsetInEndSection": 842, "text": "mmquant is a drop-in replacement of the widely used tools htseq-count and featureCounts that handles multi-mapping reads in an unabiased way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28915787", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 839, "text": "We also show the correlation for raw read counts reported by TPMCalculator, HTSeq and featureCounts", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30379987", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 1073, "text": "It features six independent core-workflows comprising the state-of-the-art technology with dozens of popular cutting-edge tools such as Tophat-Cufflink-Cuffdiff, Subread-featureCounts-DESeq2, STAR-RSEM-EBSeq, Bowtie-eXpress-edgeR, kallisto-sleuth, HISAT-StringTie-Ballgown, and embeds itself in Snakemake, which is a modern pipeline management system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28096075", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 673, "text": "SULTS: We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 672, "text": "e present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 909, "text": "t is considerably faster than existing methods (by an order of magnitude for gene-level summarization) and requires far less computer memory. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 516, "text": "Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature.R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 373, "text": "The process of counting reads is called read summarization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 650, "text": "marization. Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature.RESULTS: We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA se", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24227677", "endSection": "abstract" } ] }, { "body": "Which is the main difference in the roles of Otx2 and Nanog during development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "http://www.ncbi.nlm.nih.gov/pubmed/27292645", "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "http://www.ncbi.nlm.nih.gov/pubmed/29056334" ], "ideal_answer": [ "Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition . The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells . OTX2-mediated Nanog regulation contributes to the integrity of the ESC state and cell lineage specification in preimplantation development .", "There is a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. Through mutual antagonism, NANOG and OTX2 specify the heterogeneous identity of ESCs and individually predispose them for optimal response to naive or primed inducing factors. More specifically OTX2 impedes self-renewal of iPS cells through downregulation of NANOG expression." ], "type": "summary", "id": "5fdb4231a43ad31278000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "endSection": "title" }, { "offsetInBeginSection": 560, "offsetInEndSection": 762, "text": "Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the \"default\" rostral fate at the beginning of differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1301, "text": "a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Functional Antagonism between OTX2 and NANOG Specifies a Spectrum of\u00a0Heterogeneous Identities in Embryonic Stem Cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "title" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1037, "text": "through mutual antagonism, NANOG and OTX2 specify the heterogeneous identity of ESCs cultured in LIF\u00a0+ FBS and individually predispose them for optimal response to naive or primed inducing factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292645", "endSection": "title" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1031, "text": "Otx2-mediated Nanog regulation thus contributes to the integrity of the ESC state and cell lineage specification in preimplantation development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27292645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "OTX2 impedes self-renewal of porcine iPS cells through downregulation of NANOG expression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1359, "text": "OTX2 and NANOG can form a negative feedback circuitry to regulate the pluripotency of porcine iPS cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1301, "text": "Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1106, "text": "Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1124, "text": " NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1037, "text": "These data suggest that, through mutual antagonism, NANOG and OTX2 specify the heterogeneous identity of ESCs cultured in LIF\u00a0+ FBS and individually predispose them for optimal response to naive or primed inducing factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29386354", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Functional Antagonism between OTX2 and NANOG Specifies a Spectrum of\u00a0Heterogeneous Identities in Embryonic Stem Cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056334", "endSection": "title" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1359, "text": "These observations indicate that OTX2 and NANOG can form a negative feedback circuitry to regulate the pluripotency of porcine iPS cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27924227", "endSection": "abstract" } ] }, { "body": "Are super enhancers structurally insulated in chromatin loops?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30285185", "http://www.ncbi.nlm.nih.gov/pubmed/29507293", "http://www.ncbi.nlm.nih.gov/pubmed/28714474", "http://www.ncbi.nlm.nih.gov/pubmed/25263550" ], "ideal_answer": [ "Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements. CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target.", "Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements.", "Dissecting super-enhancer hierarchy based on chromatin interactions Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements.", "We also demonstrate that the Wap super-enhancer, which is built on STAT5 and other common transcription factors, retains its exquisite mammary specificity when placed into globally permissive chromatin, suggesting a limited role of chromatin in controlling cell specificity. CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target." ], "exact_answer": "no", "type": "yesno", "id": "5fdb42b7a43ad31278000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Dissecting super-enhancer hierarchy based on chromatin interactions", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29507293", "endSection": "title" }, { "offsetInBeginSection": 527, "offsetInEndSection": 638, "text": "Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29507293", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1409, "text": "We also demonstrate that the Wap super-enhancer, which is built on STAT5 and other common transcription factors, retains its exquisite mammary specificity when placed into globally permissive chromatin, suggesting a limited role of chromatin in controlling cell specificity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30285185", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 399, "text": "Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28714474", "endSection": "abstract" }, { "offsetInBeginSection": 909, "offsetInEndSection": 997, "text": "CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28714474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Transcription factors and chromatin-remodeling complexes are key determinants of embryonic stem cell (ESC) identity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263550", "endSection": "abstract" } ] }, { "body": "Does IL18 signaling have a role in thymus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32687059" ], "ideal_answer": [ "Yes. IL18 signaling promotes homing of mature Tregs into the thymus.", "Yes. IL18 signaling plays a key role in thymus regulation and differentiation.", "Yes. IL18 signaling plays a key role in the regulation of thymus function.", "Yes. IL18 signaling plays a crucial role in thymus regulation and differentiation." ], "exact_answer": "yes", "type": "yesno", "id": "6060e1a094d57fd879000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "IL18 signaling promotes homing of mature Tregs into the thymus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32687059", "endSection": "title" }, { "offsetInBeginSection": 771, "offsetInEndSection": 999, "text": "Collectively, this study provides a detailed characterization of the mature Treg subsets in the mouse thymus and identifies a key role of IL18 signaling in controlling the CCR6-CCL20-dependent migration of Tregs into the thymus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32687059", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 634, "text": "er, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32687059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "IL18 signaling promotes homing of mature Tregs into the thymus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32687059", "endSection": "title" }, { "offsetInBeginSection": 637, "offsetInEndSection": 771, "text": "inally, we demonstrate that IL18 signaling is critical for the induction of the key thymus-homing chemokine receptor - CCR6 on Tregs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32687059", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 635, "text": "Moreover, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32687059", "endSection": "abstract" } ] }, { "body": "Does an antiphlogistic promotes inflammation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16756015", "http://www.ncbi.nlm.nih.gov/pubmed/9595260", "http://www.ncbi.nlm.nih.gov/pubmed/125891", "http://www.ncbi.nlm.nih.gov/pubmed/28208246", "http://www.ncbi.nlm.nih.gov/pubmed/8254024", "http://www.ncbi.nlm.nih.gov/pubmed/10321035", "http://www.ncbi.nlm.nih.gov/pubmed/2806531", "http://www.ncbi.nlm.nih.gov/pubmed/7286205", "http://www.ncbi.nlm.nih.gov/pubmed/28972949", "http://www.ncbi.nlm.nih.gov/pubmed/17704978" ], "ideal_answer": [ "Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity.", "An antiphlogistic drug counteracts inflammation" ], "exact_answer": "no", "type": "yesno", "id": "601c18921cb411341a00000f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 464, "text": "The therapeutic effect of olipiphate was demonstrated for chronic inflammation of advanced arthritis and concanavalin A-related acute edema. The best systemic effect was obtained with 50 mg/kg, symptomatic--100 mg/kg. Skin wounds treated with 5% olipiphate (26 + 2) healed faster than those treated with 2% solcoseryl (30 + 0.8) or in control (33 + 0.6). It was shown histologically that the proliferative and antiphlogistic effect of olipiphate involved no scars.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16756015", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 558, "text": "Moreover, we observed an in vitro-inhibition of human neutrophil elastase, a protease involved in the inflammatory process, by extracts and fractions from yarrow, which suggests additional mechanisms of antiphlogistic action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17704978", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1076, "text": "Blood 5-HT in adrenalectomized rats with inflammationadrenalectomized rats 42 days and 3 months old with inflammation after injection of phenylbutazone an increase of 5-HT was observed, but in 18-month-old animals in which antiphlogistic action is highest a decrease of 5-HT was observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/125891", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1559, "text": "These results indicate that methotrexate is a nonsteroidal antiinflammatory agent, the antiphlogistic action of which is due to increased adenosine release at inflamed sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8254024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The antiphlogistic Ibuprofen incorporated in liposomes caused a decrease of the inflammatory edema induced by Carrageenan in the distal part of the rat's hind leg after both the intramuscular and percutaneous administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9595260", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 622, "text": "Enhancement of the immunoreactivity inhibition caused by the drugs was not proportional to the increase in their antiphlogistic effects determined by the Selye model of inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7286205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10321035", "endSection": "title" }, { "offsetInBeginSection": 875, "offsetInEndSection": 1031, "text": " investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the SPF was determined in vivo. F", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972949", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 502, "text": "Antiphlogistics were found to enhance the membrane viscosity both in control and under inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2806531", "endSection": "abstract" }, { "offsetInBeginSection": 1595, "offsetInEndSection": 1954, "text": "e in vivo determination of the SPF. Evidence of anti-inflammatory activity of the sunscreen antiphlogistics bisabolol and panthenol was also not apparent in the UV model over a time course of 48 h. Conlusion: The antiphlogistic ingredients panthenol and bisabolol incorporated in the tested sunscreen formula do not interfere with erythema reddening and thus ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972949", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 1002, "text": "nts was analyzed in vitro. To investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28972949", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 486, "text": "The aim of this study was to analyze the formation of the most relevant inflammation mediators including proteins and lipids in human fibroblasts upon inflammatory stimulation and subsequent treatment with dexamethasone, a powerful antiphlogistic drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28208246", "endSection": "abstract" } ] }, { "body": "Which interleukin receptors are targeted with rilonacept?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32550671", "http://www.ncbi.nlm.nih.gov/pubmed/32324502", "http://www.ncbi.nlm.nih.gov/pubmed/33200890", "http://www.ncbi.nlm.nih.gov/pubmed/32562029", "http://www.ncbi.nlm.nih.gov/pubmed/33229362", "http://www.ncbi.nlm.nih.gov/pubmed/25549233" ], "ideal_answer": [ "Rilonacept inhibits interleukin-1\u03b1 and interleukin-1\u03b2. It has a role for treatment of pericarditis." ], "exact_answer": [ [ "interleukin-1\u03b1" ], [ "interleukin-1\u03b2" ] ], "type": "list", "id": "601c2fb51cb411341a000013", "snippets": [ { "offsetInBeginSection": 1590, "offsetInEndSection": 1770, "text": "Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing IL-1\u03b1 and IL-1\u03b2, has also shown promising results in a phase II study in recurrent/refractory pericarditis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32324502", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1035, "text": "These agents have slightly different pharmacological properties, being canakinumab a specific IL-1\u00df antagonist while anakinra and rilonacept are unselective IL-1\u03b1 and IL-1\u00df blockers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32562029", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 797, "text": "They include agents that act against TNF\u03b1 (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol), IL-6 receptor (tocilizumab and sarilumab), IL-1 (anakinra, canakinumab, and rilonacept), IL-17 (secukinumab and ixekizumab) and IL12/23 (ustekinumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32550671", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 268, "text": "The efficacy and safety of rilonacept, an interleukin-1\u03b1 and interleukin-1\u03b2 cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33200890", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 189, "text": "Rilonacept inhibits both interleukin-1 alpha (IL-1\u03b1) and IL-1\u03b2; these cytokines are thought to play a major role in RP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33229362", "endSection": "abstract" }, { "offsetInBeginSection": 1338, "offsetInEndSection": 1425, "text": "Rilonacept is a soluble decoy receptor that neutralizes primarily IL-1\u03b2 but also IL-1\u03b1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25549233", "endSection": "abstract" } ] }, { "body": "Which deep learning framework has been developed for cancer molecular subtype classification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31420533" ], "ideal_answer": [ "Molecular subtyping of cancer is a critical step towards more individualized therapy and provides important biological insights into cancer heterogeneity. Although gene expression signature-based classification has been widely demonstrated to be an effective approach in the last decade, the widespread implementation has long been limited by platform differences, batch effects, and the difficulty to classify individual patient samples. DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. It is platform independent, robust to missing data, and can be used for single sample prediction facilitating clinical implementation of cancer molecular subtyping.", "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. It is based on deep learning of functional spectra quantifying activities of biological pathways. In two case studies about colorectal and breast cancer classification, DeepCC classifiers and DeepCC single sample predictors both achieved overall higher sensitivity, specificity, and accuracy.", "The DeepCC framework is a novel deep learning-based framework for cancer molecular subtype classification.", "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification.", "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. In two case studies about colorectal and breast cancer classification, DeepCC classifier and DeepCC single sample predictors both achieved overall higher sensitivity, specificity, and accuracy compared with other widely used classification methods such as random forests (RF), support vector machine (SVM), gradient boosting machine (GBM), and multinomial logistic regression algorithms.", "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. DeepCC is platform independent, robust to missing data, and can be used for single sample prediction." ], "exact_answer": [ "DeepCC" ], "type": "factoid", "id": "601eafcd1cb411341a000056", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "DeepCC: a novel deep learning-based framework for cancer molecular subtype classification.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420533", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1683, "text": "Molecular subtyping of cancer is a critical step towards more individualized therapy and provides important biological insights into cancer heterogeneity. Although gene expression signature-based classification has been widely demonstrated to be an effective approach in the last decade, the widespread implementation has long been limited by platform differences, batch effects, and the difficulty to classify individual patient samples. Here, we describe a novel supervised cancer classification framework, deep cancer subtype classification (DeepCC), based on deep learning of functional spectra quantifying activities of biological pathways. In two case studies about colorectal and breast cancer classification, DeepCC classifiers and DeepCC single sample predictors both achieved overall higher sensitivity, specificity, and accuracy compared with other widely used classification methods such as random forests (RF), support vector machine (SVM), gradient boosting machine (GBM), and multinomial logistic regression algorithms. Simulation analysis based on random subsampling of genes demonstrated the robustness of DeepCC to missing data. Moreover, deep features learned by DeepCC captured biological characteristics associated with distinct molecular subtypes, enabling more compact within-subtype distribution and between-subtype separation of patient samples, and therefore greatly reduce the number of unclassifiable samples previously. In summary, DeepCC provides a novel cancer classification framework that is platform independent, robust to missing data, and can be used for single sample prediction facilitating clinical implementation of cancer molecular subtyping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420533", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 645, "text": "Here, we describe a novel supervised cancer classification framework, deep cancer subtype classification (DeepCC), based on deep learning of functional spectra quantifying activities of biological pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "DeepCC: a novel deep learning-based framework for cancer molecular subtype classification", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420533", "endSection": "title" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1683, "text": "In summary, DeepCC provides a novel cancer classification framework that is platform independent, robust to missing data, and can be used for single sample prediction facilitating clinical implementation of cancer molecular subtyping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420533", "endSection": "abstract" }, { "offsetInBeginSection": 1147, "offsetInEndSection": 1448, "text": "Moreover, deep features learned by DeepCC captured biological characteristics associated with distinct molecular subtypes, enabling more compact within-subtype distribution and between-subtype separation of patient samples, and therefore greatly reduce the number of unclassifiable samples previously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420533", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 1034, "text": "In two case studies about colorectal and breast cancer classification, DeepCC classifiers and DeepCC single sample predictors both achieved overall higher sensitivity, specificity, and accuracy compared with other widely used classification methods such as random forests (RF), support vector machine (SVM), gradient boosting machine (GBM), and multinomial logistic regression algorithms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420533", "endSection": "abstract" } ] }, { "body": "What class of drugs have been given a black box warning for suicide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31130881", "http://www.ncbi.nlm.nih.gov/pubmed/19488000", "http://www.ncbi.nlm.nih.gov/pubmed/26149466", "http://www.ncbi.nlm.nih.gov/pubmed/24696870", "http://www.ncbi.nlm.nih.gov/pubmed/20222492", "http://www.ncbi.nlm.nih.gov/pubmed/23109125", "http://www.ncbi.nlm.nih.gov/pubmed/25345238", "http://www.ncbi.nlm.nih.gov/pubmed/20011576", "http://www.ncbi.nlm.nih.gov/pubmed/31136275", "http://www.ncbi.nlm.nih.gov/pubmed/17074941", "http://www.ncbi.nlm.nih.gov/pubmed/32116839", "http://www.ncbi.nlm.nih.gov/pubmed/19996040", "http://www.ncbi.nlm.nih.gov/pubmed/32587531", "http://www.ncbi.nlm.nih.gov/pubmed/21903028", "http://www.ncbi.nlm.nih.gov/pubmed/17914327" ], "ideal_answer": [ "In 2004, the European and American authorities released a black-box warning on antidepressants indicating an association with an increased risk of suicidality (suicidal ideation and behavior) in young people", "In 2004, the US Food and Drug Administration (FDA) controversially issued a black box warning that antidepressants were associated with an increased risk of suicidal thoughts and behaviours in people aged under 18 years.", "The U.S Food and Drug Administration issued a Black box warning in October 2004 after placebo-controlled trials of antidepressant medications found an increased risk of suicidal thoughts and behaviors among children and adolescents taking antidepressant medications relative to placebo." ], "exact_answer": [ "anti-depressants", "selective serotonin reuptake inhibitors", "SSRIs" ], "type": "factoid", "id": "601eab7d1cb411341a000053", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The FDA \"Black Box\" Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefit", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31130881", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31130881", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 609, "text": " However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31130881", "endSection": "abstract" }, { "offsetInBeginSection": 58, "offsetInEndSection": 267, "text": ". In 2004, the European and American authorities released a black-box warning on antidepressants indicating an association with an increased risk of suicidality (suicidal ideation and behavior) in young people", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31136275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "In 2004, the US Food and Drug Administration (FDA) controversially issued a black box warning that antidepressants were associated with an increased risk of suicidal thoughts and behaviours in people aged under 18 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32587531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "The United States Food and Drug Administration issued a Black Box warning in October 2004 after placebo-controlled trials of antidepressant medications found an increased risk of suicidal thoughts and behaviors among children and adolescents taking antidepressant medications relative to placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32116839", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 534, "text": "Subsequently, some researchers have concluded that the Black Box warning caused severe unintended consequences; specifically, they have argued that the warning led to reduced use of antidepressants among youth, which led to more suicides", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32116839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "OBJECTIVE: Isotretinoin (13-cis-retinoic acid), approved by the US Food and Drug Administration for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903028", "endSection": "abstract" }, { "offsetInBeginSection": 1232, "offsetInEndSection": 1407, "text": "There has been a decrease in the use of antidepressant therapy in children and adolescents following the US Food and Drug Administration black box warning for risk of suicide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20011576", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 191, "text": "This study evaluates changes in use of antidepressants in children and adolescents after the US Food and Drug Administration black box warning for increased risk of suicide.Method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20011576", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 535, "text": "Subsequently, some researchers have concluded that the Black Box warning caused severe unintended consequences; specifically, they have argued that the warning led to reduced use of antidepressants among youth, which led to more suicides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32116839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The FDA \"Black Box\" Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31130881", "endSection": "title" }, { "offsetInBeginSection": 184, "offsetInEndSection": 424, "text": "On July 10, 2008, a Food and Drug Administration scientific advisory committee voted that, yes, there was a significant positive association between AEDs and suicidality but voted against placing a black box warning on AEDs for suicidality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19996040", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Duty to Warn: Antidepressant Black Box Suicidality Warning Is Empirically Justified.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32116839", "endSection": "title" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1166, "text": "Food and Drug Administration has recently introduced the so-called \"black box\" on antidepressants' packages with the aim of gaining attention to the possible risk of suicide among adolescents who are treated with antidepressants, with a warning that the risk of suicide is higher when starting a therapy or while adjusting its dosage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26149466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "OBJECTIVE: Isotretinoin (13-cis-retinoic acid), approved by the US Food and Drug Administration for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psycho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903028", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 376, "text": "In 2004 the Food and Drug Administration (FDA) issued a \"black-box\" warning for antidepressants in children and adolescents, stating that these drugs may increase suicidality, a term encompassing both suicidal thoughts and behavior, especially in the first few weeks of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25345238", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 355, "text": "The US FDA has required that antidepressants carry a black box warning that there may be a risk of suicidal ideations in depressed pediatric patients treated with these medications, and recently extended the warning to include individuals up age 24.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19488000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "OBJECTIVES: To study prescribing trends for antidepressants in Hawai'i following the FDA black box warning regarding the possible risk of suicide in children and adolescents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20222492", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 772, "text": "The FDA recently linked adverse event reports of suicidal ideation among children and adolescents in randomized controlled trials to selective serotonin reuptake inhibitors (SSRIs) and consequently required a change in labeling that included a black box warning regarding SSRI use for all age groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17074941", "endSection": "abstract" }, { "offsetInBeginSection": 901, "offsetInEndSection": 1130, "text": "Another hurdle faced by new drugs is the requirement that all antidepressants carry a black-box warning regarding the increased risk of suicide in children, adolescents and young adults, which limits their use in this population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696870", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 562, "text": "The quality of studies regarding the psychopharmacological therapy of depressive disorders in childhood and adolescence has improved since the \u00abblack box\u00bb warning of the FDA concerning the occurrence of suicidality under treatment with selective serotonin reuptake inhibitors (SSRIs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23109125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31130881", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 174, "text": "To study prescribing trends for antidepressants in Hawai'i following the FDA black box warning regarding the possible risk of suicide in children and adolescents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20222492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Regulatory agencies of different European countries and the United States have been critically examining the possible link between suicidality and antidepressant use in children and adults, which has resulted in an FDA directive to the manufacturers of all antidepressant medications to add a 'black box' warning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17914327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "OBJECTIVE: Isotretinoin (13-cis-retinoic acid), approved by the US Food and Drug Administration for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21903028", "endSection": "abstract" } ] }, { "body": "What nerve is affected in Carpel Tunnel syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24886455", "http://www.ncbi.nlm.nih.gov/pubmed/31762916", "http://www.ncbi.nlm.nih.gov/pubmed/19454094", "http://www.ncbi.nlm.nih.gov/pubmed/7085815", "http://www.ncbi.nlm.nih.gov/pubmed/2307889", "http://www.ncbi.nlm.nih.gov/pubmed/3627450", "http://www.ncbi.nlm.nih.gov/pubmed/19800329", "http://www.ncbi.nlm.nih.gov/pubmed/17985535", "http://www.ncbi.nlm.nih.gov/pubmed/26721028", "http://www.ncbi.nlm.nih.gov/pubmed/32459879", "http://www.ncbi.nlm.nih.gov/pubmed/11111843", "http://www.ncbi.nlm.nih.gov/pubmed/16487634", "http://www.ncbi.nlm.nih.gov/pubmed/23727345", "http://www.ncbi.nlm.nih.gov/pubmed/29766936", "http://www.ncbi.nlm.nih.gov/pubmed/29430500", "http://www.ncbi.nlm.nih.gov/pubmed/28334999", "http://www.ncbi.nlm.nih.gov/pubmed/497808" ], "ideal_answer": [ "Carpel tunnel syndrome (CTS) is a condition in which median nerve compression results in paresthesias and pain in the wrist and hand.", "Carpel tunnel syndrome is a common compression neuropathy of the median nerve causing pain, numbness and functional dysfunction of the hand.", "Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel." ], "exact_answer": [ "median" ], "type": "factoid", "id": "601eaac81cb411341a000051", "snippets": [ { "offsetInBeginSection": 325, "offsetInEndSection": 487, "text": "An ultrasound evaluation of the carpal tunnel can assess for pathologic changes of the median nerve, detect secondary causes of CTS, and aid in surgical planning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32459879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Carpel tunnel syndrome (CTS) is a condition in which median nerve compression results in paresthesias and pain in the wrist and hand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29430500", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 392, "text": "All patients underwent ultrasound with measurement of the surface of the median nerve at the entrance of the carpal tunnel and electroneuromyographic examination of both wrists.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31762916", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 152, "text": "Carpel tunnel syndrome is a common compression neuropathy of the median nerve causing pain, numbness and functional dysfunction of the hand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26721028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Carpel tunnel syndrome is a common compression neuropathy of the median nerve causing pain, numbness and functional dysfunction of the hand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26721028", "endSection": "abstract" }, { "offsetInBeginSection": 1190, "offsetInEndSection": 1310, "text": "SION: Open carpel tunnel release surgery is an effective procedure for compression neuropathy of the median nerve. It sh", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26721028", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 785, "text": "Carpel tunnel release surgery (CTRS) was performed and in the stimulation group of patients, stainless steel electrode wires placed alongside the median nerve proximal to the surgical decompression site for immediate 1 h 20 Hz bipolar ES.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19800329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND: Carpel tunnel syndrome is a common compression neuropathy of the median nerve causing pain, numbness and functional dysfunction ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26721028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Background: Carpal tunnel syndrome refers to a constellation of symptoms resulting from compression of the median nerve ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29766936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Carpel tunnel syndrome (CTS) is a condition in which median nerve compression results in paresthesias and pain in the wrist and hand. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29430500", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 783, "text": "nslated these findings to human patients by examining the number of reinnervated motor units in the median nerve-innervated thenar muscles before and after carpel tunnel release surgery in a randomized controlled trial. Moto", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17985535", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 794, "text": "tunnel release surgery (CTRS) was performed and in the stimulation group of patients, stainless steel electrode wires placed alongside the median nerve proximal to the surgical decompression site for immediate 1 h 20 Hz bipolar ES. Subjects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19800329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "OBJECTIVES: To provide a quantitative analysis of ultrasonographic measurements and possible pathophysiology of carpal tunnel syndrome by comparing cross-sectional areas of the median nerve, carpal tunnel, and nerve/tunnel index and the difference in ultrasonographic findings between affected and nonaffected hands and between sexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23727345", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 397, "text": "We studied the SSR evoked by electrical stimulation of the median nerve and recording from the contralateral hands in 30 patients with carpal tunnel syndrome (CTS) without clinical autonomic signs and compared the results to the SSR in 30 normal controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11111843", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 489, "text": "This pattern is consistent with compression of both the anterior and posterior aspects of the median nerve in the carpal tunnel because nerve fibers responsible for thenar, lumbrical, and digit 2 functions lie in an anterior-posterior gradient within the distal median nerve.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3627450", "endSection": "abstract" }, { "offsetInBeginSection": 988, "offsetInEndSection": 1429, "text": "RESULTS: Comparison between normative (n=24) and abnormal hands (n=78) revealed the following: the mean proximal cross-sectional areas of the median nerve, carpal tunnel, and nerve/tunnel index of electrodiagnostically normative hands were 10.941mm(2), 192.43mm(2), and 5.635%, respectively, whereas those of abnormal hands were 13.74mm(2), 208.87mm(2), and 6.693%, respectively, showing statistically significant differences for all (P<.05)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23727345", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 901, "text": "Sympathetic vasomotor fibres of the median nerve are affected in carpal tunnel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16487634", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 301, "text": "The sympathetic vasomotor fibres of the median nerve were evaluated in patients with carpal tunnel syndrome and in healthy volunteers using continuous wave Doppler ultrasonography.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16487634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "INTRODUCTION: Carpal tunnel syndrome is a neuropathy caused by compression of the median nerve within the carpal tunnel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19454094", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1307, "text": "n carpel tunnel release surgery is an effective procedure for compression neuropathy of the median nerve. It", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26721028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "BACKGROUND: Carpal tunnel syndrome (CTS) is a common condition (prevalence of 4%) where the median nerve is compressed within the carpal tunnel resulting in numbness, tingling, and pain ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24886455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Background: Carpal tunnel syndrome refers to a constellation of symptoms resulting from compression of the median nerve a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29766936", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 513, "text": "The carpal tunnel syndrome usually affects women aged between 40 and 60 years, and presents typically as parasthesia of the fingers, mainly at night, in the regions served by the median nerve, sometimes associated with hypoesthesia and difficulty in movements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7085815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The carpal tunnel syndrome: localization of conduction abnormalities within the distal segment of the median nerve.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/497808", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Location of impaired sensory conduction of the median nerve in carpal tunnel syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2307889", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Carpal tunnel syndrome is the most common entrapment neuropathy, affecting the median nerve at the wrist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334999", "endSection": "abstract" } ] }, { "body": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12932294", "http://www.ncbi.nlm.nih.gov/pubmed/11776280", "http://www.ncbi.nlm.nih.gov/pubmed/15984903", "http://www.ncbi.nlm.nih.gov/pubmed/29883212", "http://www.ncbi.nlm.nih.gov/pubmed/15965816", "http://www.ncbi.nlm.nih.gov/pubmed/31818504", "http://www.ncbi.nlm.nih.gov/pubmed/20476905", "http://www.ncbi.nlm.nih.gov/pubmed/21881988", "http://www.ncbi.nlm.nih.gov/pubmed/30859382", "http://www.ncbi.nlm.nih.gov/pubmed/12715722", "http://www.ncbi.nlm.nih.gov/pubmed/12504237", "http://www.ncbi.nlm.nih.gov/pubmed/14989428", "http://www.ncbi.nlm.nih.gov/pubmed/12563672", "http://www.ncbi.nlm.nih.gov/pubmed/12196041", "http://www.ncbi.nlm.nih.gov/pubmed/12928941", "http://www.ncbi.nlm.nih.gov/pubmed/16269431", "http://www.ncbi.nlm.nih.gov/pubmed/12687534", "http://www.ncbi.nlm.nih.gov/pubmed/15082469", "http://www.ncbi.nlm.nih.gov/pubmed/12510368", "http://www.ncbi.nlm.nih.gov/pubmed/29553981", "http://www.ncbi.nlm.nih.gov/pubmed/20703489", "http://www.ncbi.nlm.nih.gov/pubmed/15172046", "http://www.ncbi.nlm.nih.gov/pubmed/15201943" ], "ideal_answer": [ "Anakinra is an oral interleukin-1 receptor antagonist that is used to treat rheumatoid arthritis.", "Anakinra is an anti-IL-1RA targeting IL-1beta with a central role in the occurrence of auto-inflammatory diseases.", "Anakinra is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that binds to and inactivates the interleukin-1 receptor (IL1R) signaling pathway and is used to treat rheumatoid arthritis", "Anakinra is an anti-IL-1RA targeting IL-1\u03b2 with a central role in the occurrence of auto-inflammatory diseases.", "Anakinra is an orally administered interleukin-1 receptor antagonist that is used to treat rheumatoid arthritis.", "Anakinra is an anti-IL-1RA targeting IL-1\u03b2 with a central role in the occurrence of auto-inflammatory diseases like rheumatoid arthritis.", "Anakinra is an anti-IL-1RA targeting IL-1\u03b2 with a central role in the occurrence of auto-inflammatory diseases" ], "exact_answer": [ "anakinra", "anti-il-1ra" ], "type": "factoid", "id": "601f08c11cb411341a00006c", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 124, "text": "Anakinra is an anti-IL-1RA targeting IL-1\u03b2 with a central role in the occurrence of auto-inflammatory diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31818504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "(1) Anakinra is an interleukin-1 receptor antagonist (IL-1ra), which blocks interleukin-1 (IL-1), a protein involved in the inflammation and the joint destruction associated with rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11776280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "[The safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid arthritis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15201943", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The use of anakinra, an interleukin-1 receptor antagonist, in the treatment of rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15172046", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 343, "text": "One of these molecules is interleukin-1 receptor antagonist (Anakinra; Amgen Corp.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29553981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "INTRODUCTION: The anti-interleukin-1 receptor antagonist, anakinra, was approved for the treatment of rheumatoid arthritis (RA) more than 12\u00a0ye", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29883212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Anakinra, the recombinant form of IL-1 receptor antagonist (IL-1Ra), has been approved for clinical use in the treatment of rheumatoid arthritis as the drug Kineret trade mark, but it must be administered daily by subcutaneous injection. Gene ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12932294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND: The efficacy and safety of anakinra, a recombinant human interleukin 1 (IL1) receptor antagonist used in rheumatoid arthritis, has been documented in five randomised controlled st", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16269431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21881988", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 216, "text": ") Anakinra is an interleukin-1 receptor antagonist (IL-1ra), which blocks interleukin-1 (IL-1), a protein involved in the inflammation and the joint destruction associated with rheumatoid arthritis (RA). (2) The ma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11776280", "endSection": "abstract" }, { "offsetInBeginSection": 1479, "offsetInEndSection": 1768, "text": "The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15965816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Anakinra is a specific receptor antagonist of interleukin-1 that differs from naturally occurring interleukin-1 receptor antagonist by the presence of a methionine group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20476905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Anakinra, a recombinant human interleukin-1 (IL-1) receptor antagonist, is the first biological agent approved to block the pro-inflammatory effects of IL-1 in patients with rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12196041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "BACKGROUND: Anakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30859382", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 382, "text": "The first IL-1 antagonist to be approved for RA was Anakinra, an IL-1 receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20703489", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 558, "text": "Two randomized, multicenter clinical trials with anakinra, a recombinant IL-1 receptor antagonist (rHHHuIL-1Ra), revealed that application of anakinra with or without methotrexate induces remission (ACR 20) in 38-71% of patients with RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12715722", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 251, "text": "Anakinra (Kineret) is an IL-1 receptor antagonist that blocks the biologic activity of IL-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15172046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Interleukin 1 receptor antagonist anakinra improves functional status in patients with rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12563672", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 259, "text": "This study evaluated the benefit of anakinra, a human recombinant form of interleukin 1 receptor antagonist, on the functional status of patients with active rheumatoid arthritis (RA) despite taking maximally tolerated doses of methotrexate (MTX).M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12563672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "OBJECTIVE: To evaluate the safety of anakinra (a recombinant human interleukin-1 receptor antagonist) in a large population of patients with rheumatoid arthritis (RA), typical of those seen in clinical practice.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12687534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Anakinra, a recombinant human interleukin-1 receptor antagonist offers a new potent treatment for rheumatoid arthritis(RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12510368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Anakinra is a recombinant human interleukin-1 receptor antagonist (IL-1ra) recently approved by the FDA as a new therapy for patients with rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14989428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "[Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12510368", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Safety of anakinra, a recombinant interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis and comparison to anti-TNF-alpha agents.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14989428", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "PURPOSE: Interleukin -1 receptor antagonist ( IL-1Ra ) is a new option among biotherapies against rheumatoid arthritis ( RA ).THE AIM: of this review is to recall the rationale of use of IL-1Ra and to analyse the results available in the current literature.CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiological data of RA give a specific position for IL-1 as a potential target for immuno", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12504237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Anakinra (Kineret) is the first biologic drug that has been developed specifically as an interleukin (IL)-1 receptor antagonist (Ra) and is derived from an endogenous IL-1Ra.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15984903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12687534", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "OBJECTIVE: To evaluate the safety of anakinra (a recombinant human interleukin-1 receptor antagonist) in a large population of patients with rheumatoid arthritis (RA), typical of those seen in clinical practice.METHODS: A total of 1,414 patients were randomly assigned to treatment with 100 mg of anakinra or placebo, administered daily by sub", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12687534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "OBJECTIVE: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA).METHODS: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, place", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15082469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "[Interleukin-1 receptor antagonist anakinra (Kineret) for treatment of rheumatic arthritis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12928941", "endSection": "title" } ] }, { "body": "Herpes viruses have what type of genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17296606", "http://www.ncbi.nlm.nih.gov/pubmed/10627574", "http://www.ncbi.nlm.nih.gov/pubmed/26121674", "http://www.ncbi.nlm.nih.gov/pubmed/16160176", "http://www.ncbi.nlm.nih.gov/pubmed/12716057", "http://www.ncbi.nlm.nih.gov/pubmed/21390711", "http://www.ncbi.nlm.nih.gov/pubmed/22020814", "http://www.ncbi.nlm.nih.gov/pubmed/10774200", "http://www.ncbi.nlm.nih.gov/pubmed/21491367", "http://www.ncbi.nlm.nih.gov/pubmed/1652278", "http://www.ncbi.nlm.nih.gov/pubmed/9514102", "http://www.ncbi.nlm.nih.gov/pubmed/18687114" ], "ideal_answer": [ "The Herpesviridae are a family of viruses which have a large genome of linear, double-stranded DNA (> 120 kb)", "The genome of Herpes viruses is composed of linear, double-stranded DNA.", "Herpes simplex virus 1 (HSV-1) and HSV-2 are nuclear-replicating viruses composed of a double-stranded DNA genome", "Herpes simplex virus 1 (HSV-1) has a double-stranded linear DNA genome that is approximately 152 kbp in length.", "Herpesviridae are a family of viruses which have a large genome of linear, double-stranded DNA.", "Herpes viruses have a linear, double-stranded DNA genome." ], "exact_answer": [ "double stranded DNA" ], "type": "factoid", "id": "601f105e1cb411341a000071", "snippets": [ { "offsetInBeginSection": 149, "offsetInEndSection": 263, "text": "Herpes simplex virus 1 (HSV-1) and HSV-2 are nuclear-replicating viruses composed of a double-stranded DNA genome ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22020814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 670, "text": "Vectors derived from herpes simplex virus provide a means of gene delivery to postmitotic neurons. The virus is readily taken up at nerve terminals, passes by rapid retrograde and anterograde transport within neurons, and is selectively transferred across synapses, thus allowing it entry from the periphery into the brain. This virus can enter a state of latency in some neurons, where it exists as an episomal element in the nucleus and is transcriptionally active to a reduced extent. In this state, the virus is apparently benign and can effect stable expression of foreign genes. The large (150 kb) genome of this double-stranded virus has been completely sequenced", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1652278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "The Herpesviridae are a family of viruses which have a large genome of linear, double-stranded DNA (> 120 kb)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10774200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Herpesviruses have large double-stranded linear DNA genomes that are formed by site-specific cleavage from complex concatemeric intermediates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10627574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "BACKGROUND: Herpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of approximatel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Human cytomegalovirus (HCMV) is a double-stranded DNA virus with the largest genome (~235 kb) of the known human herpes viruses. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21491367", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 746, "text": "quence-independent nuclear innate sensor ALR, recognizes episomal dsDNA genomes of herpes viruses such as KSHV, EBV, and HSV-1 in the infected cell nuclei, forms an inflammasome complex with ASC and procaspase1, and relocates into the cytoplasm leading into Caspase-1 and IL-1\u03b2 generation. IFI16 also indu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26121674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "For many years, the generally accepted model for the replication of the double-stranded DNA genome of herpes simplex virus type 1 (HSV-1) incorporated initial circularization of linear molecules in the cell nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16160176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) are doublestranded DNA viruses with a genome size of 152 kbp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21390711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Herpes simplex virus has a linear double-stranded DNA genome with directly repeated terminal sequences needed for cleavage and packaging of replicated DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17296606", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 463, "text": "Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9514102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Herpesviruses are large double stranded DNA animal viruses with the distinguishing ability to establish latent, life-long infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12716057", "endSection": "abstract" } ] }, { "body": "Is liraglutide effective for weight reduction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19930006", "http://www.ncbi.nlm.nih.gov/pubmed/25202980", "http://www.ncbi.nlm.nih.gov/pubmed/19436648", "http://www.ncbi.nlm.nih.gov/pubmed/17039422", "http://www.ncbi.nlm.nih.gov/pubmed/27073422", "http://www.ncbi.nlm.nih.gov/pubmed/27600499", "http://www.ncbi.nlm.nih.gov/pubmed/32506681", "http://www.ncbi.nlm.nih.gov/pubmed/25237400", "http://www.ncbi.nlm.nih.gov/pubmed/27995594", "http://www.ncbi.nlm.nih.gov/pubmed/32410565", "http://www.ncbi.nlm.nih.gov/pubmed/26284720", "http://www.ncbi.nlm.nih.gov/pubmed/32233338", "http://www.ncbi.nlm.nih.gov/pubmed/30678612", "http://www.ncbi.nlm.nih.gov/pubmed/31770497", "http://www.ncbi.nlm.nih.gov/pubmed/31203802", "http://www.ncbi.nlm.nih.gov/pubmed/32202085" ], "ideal_answer": [ "Yes, liraglutide is effective and approved for weight reduction." ], "exact_answer": "yes", "type": "yesno", "id": "6020ad161cb411341a000082", "snippets": [ { "offsetInBeginSection": 1272, "offsetInEndSection": 1330, "text": "Liraglutide has been approved at higher dose for obesity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30678612", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1332, "text": "This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; \u2206 -3.07 Kg, 95% CI, -3.76 to -2.37), phentermine plus topiramate (N = 2985; \u2206 -9.77 Kg; 95% CI, -11.73 to -7.81), lorcaserin (N = 16,856; \u2206 -3.08 Kg; 95% CI, -3.49 to -2.66), naltrexone plus bupropion (N = 3239; \u2206 -4.39 Kg; 95% CI, -5.05 to -3.72) and liraglutide (N = 4978; \u2206 -5.25 Kg; 95% CI, -6.17 to -4.32), compared to placebo (all p < 0.00001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31770497", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1771, "text": "CONCLUSION: In patients with T1D, liraglutide might prove be an adjunct to insulin, improving glycemic control, inducing body weight loss and decreasing exogenous insulin requirements and severe hypoglycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31203802", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 1001, "text": "Data from most recent meta-analyses showed that the overall placebo-subtracted weight reduction (%) with the use of anti-obesity drugs for at least 12 months ranges from 2.9% to 6.8%; phentermine/topiramate (-6.8%) liraglutide (-5.4%), naltrexone/bupropion (-4.0%), lorcaserin (-3.1%), and orlistat (-2.9%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32202085", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 1027, "text": "RESULTS: Currently, the FDA has approved several molecules for the treatment of obesity, both in monotherapy and in combination. Pharmacological monotherapies focus mainly on a single protein target and include orlistat, lorcaserin and liraglutide while the combination molecules propose a multitarget approach and include phentermine/topiramate and naltrexone/bupropion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32410565", "endSection": "abstract" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1285, "text": "Phentermine-topiramate and liraglutide have been associated with the highest probability of at least 5% weight loss. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32410565", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 206, "text": "Currently, high-dose liraglutide has been used for weight control in non-diabetic patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32506681", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1533, "text": "CONCLUSIONS: Low-dose liraglutide still has high efficacy in weight reduction in Taiwanese people, especially for those of younger age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32506681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BACKGROUND: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been shown to possess pleiotropic effects including body weight reduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25237400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 413, "text": "INTRODUCTION: For people with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs (OADs), evidence from both randomized controlled trials (RCTs) and real-world studies has demonstrated that treatment intensification with liraglutide offers effective glycemic control, weight reduction, and a lower risk of hypoglycemia compared to treatment intensification with insulin or additional OADs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27995594", "endSection": "abstract" }, { "offsetInBeginSection": 1544, "offsetInEndSection": 1795, "text": "wise regression analysis demonstrated that baseline BMI and previous insulin dose were positively associated with body weight reduction and baseline HbA1c was positively associated with reduction of HbA1c at 2\u00a0years after liraglutide introduction.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25237400", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 1001, "text": " control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP. Moreover, liraglutide comb", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Hig", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27073422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Liraglutide, a glucagon-like peptide (GLP-1) receptor agonist, has showed favorable effects in the glycaemic control and weight reduction in patients with type 2 diabetes mellitus (T2DM). The me", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27600499", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 555, "text": "Here, we determined that liraglutide does not activate GLP-1-producing neurons in the hindbrain, and liraglutide-dependent body weight reduction in rats was independent of GLP-1 receptors (GLP-1Rs) in the vagus nerve, area postrema, and paraventricular nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25202980", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 999, "text": "Liraglutide is associated with body weight loss, and reductions in systolic blood pressure have been observed throughout the clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19436648", "endSection": "abstract" }, { "offsetInBeginSection": 2492, "offsetInEndSection": 2690, "text": "CONCLUSIONS AND RELEVANCE: Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26284720", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1684, "text": "CONCLUSION: Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19930006", "endSection": "abstract" }, { "offsetInBeginSection": 2259, "offsetInEndSection": 2469, "text": "CONCLUSIONS: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32233338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17039422", "endSection": "title" }, { "offsetInBeginSection": 1441, "offsetInEndSection": 1529, "text": "In the latter case, body weight was reduced in comparison to metformin plus glimepiride.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17039422", "endSection": "abstract" } ] }, { "body": "Is lorcaserin associated with increased cancer risk?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33258543" ], "ideal_answer": [ "The US Food and Drug Administration (FDA) reported an increased risk of cancer with lorcaserin in the follow-up of the CAMELLIA-TIMI 61 trial. However, subsequent meta-analysis did not confirm the increased risk of cancer with lorcaserin but suggests a trend in this direction, with a greater incidence of some subtypes such as lung and pancreas." ], "type": "summary", "id": "6020ae4c1cb411341a000083", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Is lorcaserin really associated with increased risk of cancer? A systematic review and meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33258543", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The US Food and Drug Administration (FDA) reported in February 2020 an increased risk of cancer with lorcaserin in the follow-up of the CAMELLIA-TIMI 61 trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33258543", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 1120, "text": "From 11 trials, comprising 21,299 individuals, four studies were included in the meta-analysis and reported 476 cases of cancer in 10,342 subjects in the lorcaserin group and 438 among 9429 individuals randomized to placebo (relative risk [RR]: 1.08; 95% confidence interval [95% CI]: 0.96-1.23). The result was heavily influenced by the CAMELLIA-TIMI 61 trial. In this study, the lorcaserin group had a higher risk of lung and pancreatic but not colon cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33258543", "endSection": "abstract" }, { "offsetInBeginSection": 1188, "offsetInEndSection": 1379, "text": "The current evidence does not confirm the increased risk of cancer with lorcaserin but suggests a trend in this direction, with a greater incidence of some subtypes such as lung and pancreas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33258543", "endSection": "abstract" } ] }, { "body": "Is Eflornithine and Sulindac are effective for prevention of progression in Familial Adenomatous Polyposis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32905675" ], "ideal_answer": [ "No. In a clinical trial, the incidence of progression in Familial Adenomatous Polyposis was not significantly lower with the combination of eflornithine and sulindac than with either drug alone." ], "exact_answer": "no", "type": "yesno", "id": "6020b0e21cb411341a000085", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905675", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905675", "endSection": "abstract" }, { "offsetInBeginSection": 2296, "offsetInEndSection": 2523, "text": "CONCLUSIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905675", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1589, "text": "Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P\u2009=\u20090.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905675", "endSection": "abstract" }, { "offsetInBeginSection": 2302, "offsetInEndSection": 2528, "text": "SIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Fund", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905675", "endSection": "abstract" }, { "offsetInBeginSection": 2312, "offsetInEndSection": 2525, "text": "this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (F", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905675", "endSection": "abstract" } ] }, { "body": "Which cancer can be treated with Darolutamide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32905676", "http://www.ncbi.nlm.nih.gov/pubmed/31571146", "http://www.ncbi.nlm.nih.gov/pubmed/32282865", "http://www.ncbi.nlm.nih.gov/pubmed/31582533", "http://www.ncbi.nlm.nih.gov/pubmed/33237495", "http://www.ncbi.nlm.nih.gov/pubmed/32073798", "http://www.ncbi.nlm.nih.gov/pubmed/28851578", "http://www.ncbi.nlm.nih.gov/pubmed/33226524", "http://www.ncbi.nlm.nih.gov/pubmed/32456317", "http://www.ncbi.nlm.nih.gov/pubmed/32430485", "http://www.ncbi.nlm.nih.gov/pubmed/32822968", "http://www.ncbi.nlm.nih.gov/pubmed/31972568", "http://www.ncbi.nlm.nih.gov/pubmed/32125151", "http://www.ncbi.nlm.nih.gov/pubmed/31605368", "http://www.ncbi.nlm.nih.gov/pubmed/31571095", "http://www.ncbi.nlm.nih.gov/pubmed/30763142", "http://www.ncbi.nlm.nih.gov/pubmed/31953000", "http://www.ncbi.nlm.nih.gov/pubmed/30824428", "http://www.ncbi.nlm.nih.gov/pubmed/32278840", "http://www.ncbi.nlm.nih.gov/pubmed/33141615", "http://www.ncbi.nlm.nih.gov/pubmed/33135506", "http://www.ncbi.nlm.nih.gov/pubmed/32534790", "http://www.ncbi.nlm.nih.gov/pubmed/32924096", "http://www.ncbi.nlm.nih.gov/pubmed/32605736", "http://www.ncbi.nlm.nih.gov/pubmed/32436836", "http://www.ncbi.nlm.nih.gov/pubmed/31695432" ], "ideal_answer": [ "Darolutamide is used for treatment of nonmetastatic castration-resistant prostate cancer." ], "exact_answer": [ "Nonmetastatic castration-resistant prostate cancer" ], "type": "factoid", "id": "6020b2b21cb411341a000086", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Lately the development of 3 novel second-generation androgen receptor antagonists (enzalutamide, apalutamide, and darolutamide) chanced the treatment landscape of nonmetastatic castration-resistant prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31953000", "endSection": "abstract" }, { "offsetInBeginSection": 1672, "offsetInEndSection": 1897, "text": "CONCLUSION: Our outcomes support equivalent efficacy and similar risk of adverse effects between apalutamide, enzalutamide, and darolutamide, supporting the use of these antiandrogen agents in high-risk of progression nmCRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31972568", "endSection": "abstract" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1410, "text": "Furthermore, the combination of BAY 1895344 with the novel, nonsteroidal androgen receptor antagonist darolutamide resulted in significantly improved antitumor efficacy compared with respective single-agent treatments in hormone-dependent prostate cancer, and addition of EBRT resulted in even further enhanced antitumor efficacy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31582533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The antiandrogen therapeutics apalutamide and darolutamide entered the clinic in 2018 and 2019, respectively, for the treatment of castration-resistant prostate cancer (CRPC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32125151", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1085, "text": "This has been further verified by the recent FDA approval of the other two second-generation AR antagonists, apalutamide and darolutamide, for the treatment of prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32456317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "The next-generation antiandrogen drugs, XTANDI (enzalutamide), ZYTIGA (abiraterone acetate), ERLEADA (apalutamide) and NUBEQA (darolutamide) extend survival times and improve quality of life in patients with advanced prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32430485", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND: Darolutamide is recently approved for the treatment of non-metastatic castrate resistance prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32436836", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 369, "text": "Multiple agents including abiraterone, enzalutamide, apalutamide, darolutamide, docetaxel, cabazitaxel, radium-223, and sipuleucel-T have been approved for advanced prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32534790", "endSection": "abstract" }, { "offsetInBeginSection": 2088, "offsetInEndSection": 2307, "text": "CONCLUSIONS: NSAAs improve survival in high-risk nmCRPC. Apalutamide and enzalutamide may result in improved oncologic outcomes. Darolutamide may result in fewer AEs. Phase IV data are needed to validate these findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32278840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Darolutamide for treatment of castration-resistant prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32282865", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Darolutamide is a novel, nonsteroidal androgen receptor (AR)-signaling inhibitor. It serves as a second-generation antiandrogen and is currently indicated for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32282865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "BACKGROUND: Darolutamide, a structurally distinct androgen receptor inhibitor approved for the treatment of men with nonmetastatic castration-resistant prostate cancer (nmCRPC), has been shown to increase metastasis-free survival among men with nmCRPC compared with placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33141615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Budget impact analysis of darolutamide for treatment of nonmetastatic castration-resistant prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33141615", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "BACKGROUND: Darolutamide, an androgen receptor antagonist with a distinct molecular structure, significantly prolonged metastasis-free survival versus placebo in the phase III ARAMIS study in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31571095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30763142", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "BACKGROUND: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33226524", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 349, "text": "Based on positive results in the phase III ARAMIS trial, darolutamide was recently approved in the USA for the treatment of men with non-metastatic castration-resistant prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31605368", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 489, "text": "Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28851578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "BACKGROUND: Darolutamide, a structurally distinct androgen receptor inhibitor approved for the treatment of men with nonmetastatic castration-resistant prostate cancer (nmCRPC), has been shown to increase metastasis-free survival among men with nmCRPC compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33141615", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 685, "text": "For non-metastatic castration-resistant prostate cancer, recent phase III placebo-controlled trials with enzalutamide, apalutamide and darolutamide all demonstrated benefits in improving metastasis-free survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31695432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Darolutamide For Castration-Resistant Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31695432", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "The results of a recent randomised phase 3 clinical trial show that the androgen receptor antagonist darolutamide improves metastasis-free survival in men with non-metastatic, castration-resistant prostate cancer, compared with placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32073798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Comparative efficacy of apalutamide darolutamide and enzalutamide for treatment of non-metastatic castrate-resistant prostate cancer: A systematic review and network meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32605736", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "INTRODUCTION: Studies using apalutamide, enzalutamide, or darolutamide have shown improved metastasis free survival (MFS) rates, leaving clinicians with a dilemma of choosing one over the other, for nonmetastatic castration recurrent prostate cancer (nmCRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32605736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "BACKGROUND AND OBJECTIVES: Darolutamide is a novel androgen receptor (AR) antagonist approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31571146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Apalutamide, enzalutamide, and darolutamide for non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32924096", "endSection": "title" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1719, "text": "Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32924096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33237495", "endSection": "title" }, { "offsetInBeginSection": 207, "offsetInEndSection": 579, "text": " In the pivotal multinational, phase 3 ARAMIS trial in men with nmCRPC, relative to placebo plus ongoing androgen deprivation therapy (ADT), darolutamide (+ ADT) significantly prolonged metastasis-free survival (MFS) at the time of the primary analysis and overall survival (OS) at the time of the final OS analysis and was generally well tolerated in extended follow-up. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33237495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The phase III ARAMIS study shows that the androgen-receptor antagonist darolutamide delays metastasis in men with castration-resistant prostate cancer by a median of 22 months compared with a placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30824428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Since 2018, apalutamide, darolutamide, and enzalutamide have been approved for the treatment of men with non-metastatic castration-resistant prostate cancer (M0CRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32822968", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 361, "text": "Apalutamide, enzalutamide, and most recently, darolutamide (novel androgen receptor antagonists) have been approved for nonmetastatic castration-resistant prostate cancer (nmCRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33135506", "endSection": "abstract" } ] }, { "body": "Which cancers can be treated with Selpercatinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33150799", "http://www.ncbi.nlm.nih.gov/pubmed/33007380", "http://www.ncbi.nlm.nih.gov/pubmed/33272981", "http://www.ncbi.nlm.nih.gov/pubmed/33161056", "http://www.ncbi.nlm.nih.gov/pubmed/32493697", "http://www.ncbi.nlm.nih.gov/pubmed/32557397", "http://www.ncbi.nlm.nih.gov/pubmed/33082208", "http://www.ncbi.nlm.nih.gov/pubmed/33239432", "http://www.ncbi.nlm.nih.gov/pubmed/31988000", "http://www.ncbi.nlm.nih.gov/pubmed/32846061", "http://www.ncbi.nlm.nih.gov/pubmed/32846060", "http://www.ncbi.nlm.nih.gov/pubmed/33169506" ], "ideal_answer": [ "Selpercatinib was recently approved by the US FDA for the treatment of RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer." ], "exact_answer": [ [ "non-small-cell lung cancer" ], [ "thyroid cancer" ], [ "medullary thyroid cancer" ] ], "type": "list", "id": "6020b8811cb411341a000089", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND: Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small cell lung cancer (NSCLC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33161056", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 443, "text": "Based on results from the phase I/II LIBRETTO-001 trial, selpercatinib was recently approved by the US FDA for the treatment of RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32557397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The FDA has greenlighted selpercatinib, the first targeted therapy for RET-altered non-small cell lung cancer (NSCLC) and certain types of thyroid cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32493697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "INTRODUCTION: Novel rearranged in transfection (RET)-specific tyrosine kinase inhibitors (TKIs) such as selpercatinib (LOXO-292) have shown unprecedented efficacy in tumors positive for RET fusions or mutations, notably RET fusion-positive NSCLC and RET-mutated medullary thyroid cancer (MTC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31988000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Neoadjuvant selpercatinib for advanced medullary thyroid cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33169506", "endSection": "title" }, { "offsetInBeginSection": 153, "offsetInEndSection": 343, "text": "Recently, highly potent next generation selective RET inhibitors have been clinically validated, and selpercatinib was recently Food and Drug Administration (FDA)-approved for advanced MTC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33169506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "PURPOSE: Selpercatinib and pralsetinib induce deep and durable responses in advanced RET fusion-positive lung and thyroid cancer patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33272981", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 402, "text": "RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33007380", "endSection": "abstract" }, { "offsetInBeginSection": 1809, "offsetInEndSection": 2027, "text": "CONCLUSIONS: In this phase 1-2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32846061", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Overcoming MET-Dependent Resistance to Selective RET Inhibition in Patients with RET Fusion-Positive Lung Cancer by Combining Selpercatinib with Crizotinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33082208", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "BACKGROUND: Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small cell lung cancer (NSCLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33161056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 617, "text": "On May 8, 2020, the Food and Drug Administration granted accelerated approval to selpercatinib for 1) adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), 2) adult and pediatric patients \u226512 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and 3) adult and pediatric patients \u226512 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Approval was granted based on the clinically importa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33239432", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 452, "text": " on results from the phase I/II LIBRETTO-001 trial, selpercatinib was recently approved by the US FDA for the treatment of RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer. This art", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32557397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Selpercatinib, a novel, highly selective and potent, inhibitor of RET, demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pretreated and treatment-naive RET fusion-positive\u00a0non-small-cell lung cancer patients in a Phase I/II clinical tr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33150799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "The FDA has greenlighted selpercatinib, the first targeted therapy for RET-altered non-small cell lung cancer (NSCLC) and certain types of thyroid cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32493697", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "BACKGROUND: Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small cell lung cancer (NSCL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33161056", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 400, "text": "NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33007380", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 608, "text": "ial. LIBRETTO-431 (NCT04194944) is a randomized, global, multicenter, open-label, Phase III trial, evaluating selpercatinib versus carboplatin or cisplatin and pemetrexed chemotherapy with or without pembrolizumab in treatment-naive patients with locally advanced/metastatic RET fusion-positive nonsquamous non-small-cell lung cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33150799", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 357, "text": "Selpercatinib is a highly selective RET kinase inhibitor that has recently been approved by the FDA in lung and thyroid cancers with activating RET gene fusions and mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33082208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "BACKGROUND: Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small cell lung can", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33161056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 564, "text": "On May 8, 2020, the Food and Drug Administration granted accelerated approval to selpercatinib for 1) adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), 2) adult and pediatric patients \u226512 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and 3) adult and pediatric patients \u226512 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33239432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Selpercatinib, a novel, highly selective and potent, inhibitor of RET, demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pretreated and treatment-naive RET fusion-positive\u00a0non-small-cell lung cancer patients in a Phase I/II clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33150799", "endSection": "abstract" }, { "offsetInBeginSection": 1743, "offsetInEndSection": 2001, "text": "CONCLUSIONS: Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32846060", "endSection": "abstract" } ] }, { "body": "What is the target of Volanesorsen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31390883", "http://www.ncbi.nlm.nih.gov/pubmed/29889589", "http://www.ncbi.nlm.nih.gov/pubmed/32753844", "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "http://www.ncbi.nlm.nih.gov/pubmed/32589506", "http://www.ncbi.nlm.nih.gov/pubmed/28595549", "http://www.ncbi.nlm.nih.gov/pubmed/29096837", "http://www.ncbi.nlm.nih.gov/pubmed/31390500", "http://www.ncbi.nlm.nih.gov/pubmed/32646313", "http://www.ncbi.nlm.nih.gov/pubmed/30403015", "http://www.ncbi.nlm.nih.gov/pubmed/32511037", "http://www.ncbi.nlm.nih.gov/pubmed/28300080", "http://www.ncbi.nlm.nih.gov/pubmed/32494907", "http://www.ncbi.nlm.nih.gov/pubmed/31301033", "http://www.ncbi.nlm.nih.gov/pubmed/29124482", "http://www.ncbi.nlm.nih.gov/pubmed/31032598", "http://www.ncbi.nlm.nih.gov/pubmed/30596391" ], "ideal_answer": [ "Volanesorsen is a second-generation antisense oligonucleotide inhibiting apoC-III (apolipoprotein C-III) transcription/translation that has been recently approved in Europe for Familial Chylomicronemia Syndrome (FCS) treatment." ], "exact_answer": [ "apoC-III" ], "type": "factoid", "id": "602343051cb411341a00008d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Treatment with Volanesorsen, a 2'-O-Methoxyethyl-Modified Antisense Oligonucleotide Targeting APOC3", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589506", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Evaluation of efficacy and safety of antisense inhibition of apolipoprotein C-III with volanesorsen in patients with severe hypertriglyceridemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32646313", "endSection": "title" }, { "offsetInBeginSection": 532, "offsetInEndSection": 736, "text": "Volanesorsen is a second-generation antisense oligonucleotide inhibiting apoC-III transcription/translation that has been recently approved in Europe for Familial Chylomicronemia Syndrome (FCS) treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32646313", "endSection": "abstract" }, { "offsetInBeginSection": 957, "offsetInEndSection": 1205, "text": "Volanesorsen is an antisense oligonucleotide (ASO) inhibitor of apoC3, which reduces TG levels by 70-80% which has been shown also to reduce rates of pancreatitis and improve well-being in FCS and reduce TGs and improve insulin resistance in FPLD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753844", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 979, "text": "Volanesorsen targeting apoC-III has shown reductions in plasma TG levels up to 90%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32511037", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1405, "text": "CENT FINDINGS: Evidence is now emerging that volanesorsen, a second-generation antisense oligonucleotide drug targeting ApoCIII messenger RNA resulting in decreases in TG in patients with familial chylomicronemia syndrome, severe hypertriglyceridemia, and metabolic dyslipidemia with type 2 diabetes giving support to the hypothesis that ApoCIII is a powerful inhibitor of LPL, and when reduced, endogenous clearance of TRLs can result in substantial reductions in TG levels. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29124482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "OBJECTIVE: To determine the effects of volanesorsen (ISIS 304801), a second-generation 2'-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein (apo)C-III, on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27271183", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 689, "text": "ariants. As such, apoC-III has been recognised as a potential therapeutic target for patients with severe hypertriglyceridaemia with one of the most promising apoC-III-targeting drugs, volanesorsen, having recently progressed through Phase III ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32494907", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 968, "text": "Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30403015", "endSection": "abstract" }, { "offsetInBeginSection": 1216, "offsetInEndSection": 1334, "text": "Some new drugs are on the horizon, such as volanesorsen (which targets apolipoprotein C-III), pemafibrate, and others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28300080", "endSection": "abstract" }, { "offsetInBeginSection": 752, "offsetInEndSection": 929, "text": "Volanesorsen is an experimental antisense oligonucleotide that inhibits translation of Apo-CIII mRNA, thereby substantially lowering plasma levels of Apo-CIII and triglycerides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30596391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 619, "text": "BACKGROUND: Volanesorsen, an investigational inhibitor of apoC-III synthesis, significantly reduced triglyceride levels in clinical trials in patients with familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by marked chylomicronemia leading to a spectrum of symptoms, including recurrent abdominal pain and episodes of potentially fatal acute pancreatitis (AP).OBJECTIVE: To determine the effect of volanesorsen on burden of disease on patients with FCS Methods: ReFOCUS was a retrospective global web-based survey open to patients with FCS who received volanesorsen for \u22653\u00a0months in an open", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29889589", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 438, "text": " In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic APOC3 mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31390500", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Volanesorsen (Waylivra\u00ae), an antisense oligonucleotide inhibitor of apolipoprotein CIII (apoCIII) mRNA, is being developed by Ionis Pharmaceuticals through its subsidiary company, Akcea Therapeutics, to treat familial chylomicronemia syndrome (FCS), hypertriglyceridemia and familial partial lipodystrophy (FPL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31301033", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 892, "text": " Recently, volanesorsen as a promising ApoIII inhibitor was shown to improve the lipid profile in patients with diabetic dyslipidemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31032598", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1002, "text": "he antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apoC-III production and triglyceride concentrations and is being currently evaluated in phase 3 trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28595549", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 991, "text": "The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apo-CIII production and triglyceride concentrations and is being currently evaluated in phase 3 trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29096837", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 447, "text": "et, it remains unclear whether apoC-III glycosylation impacts TRL (triglyceride-rich lipoprotein) clearance and whether apoC-III antisense therapy (volanesorsen) affects distribution of apoC-III glycoforms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31390883", "endSection": "abstract" } ] }, { "body": "Roflumilast Cream is effective for which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33197348", "http://www.ncbi.nlm.nih.gov/pubmed/32668113", "http://www.ncbi.nlm.nih.gov/pubmed/27038440", "http://www.ncbi.nlm.nih.gov/pubmed/32845114" ], "ideal_answer": [ "Roflumilast Cream has been shown to be effective for psoriasis." ], "exact_answer": [ "psoriasis" ], "type": "factoid", "id": "6023518f1cb411341a000097", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Trial of Roflumilast Cream for Chronic Plaque Psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668113", "endSection": "title" }, { "offsetInBeginSection": 2163, "offsetInEndSection": 2442, "text": "CONCLUSIONS: Roflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Roflumilast Cream Improves Signs and Symptoms of Plaque Psoriasis: Results from a Phase 1/2a Randomized, Controlled Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32845114", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Background: Roflumilast cream (ARQ-151) is a highly potent, selective phosphodiesterase-4 inhibitor in development for once-daily topical treatment of chronic plaque psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32845114", "endSection": "abstract" }, { "offsetInBeginSection": 1536, "offsetInEndSection": 1729, "text": "Conclusion: Roflumilast cream was safe and highly effective at doses of 0.5% and 0.15% and represents a potential novel once-daily topical therapy for the treatment of chronic plaque psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32845114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "In chronic plaque psoriasis, roflumilast cream safely increased likelihood of clear or almost clear state at 6 weeks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33197348", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "SOURCE CITATION: Lebwohl MG, Papp KA, Stein Gold L, et al. Trial of roflumilast cream for chronic plaque psoriasis. N Engl J Med. 2020;383:229-39. 32668113.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33197348", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1758, "text": "CONCLUSIONS: Topical treatment with cream formulations of the PDE4 inhibitors roflumilast and TAK-084 reduced inflammation, measured as a change in skin infiltrate thickness, and reduced psoriasis severity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27038440", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of Givosiran.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "http://www.ncbi.nlm.nih.gov/pubmed/32521132", "http://www.ncbi.nlm.nih.gov/pubmed/32311310", "http://www.ncbi.nlm.nih.gov/pubmed/32929000", "http://www.ncbi.nlm.nih.gov/pubmed/32034693", "http://www.ncbi.nlm.nih.gov/pubmed/32561705", "http://www.ncbi.nlm.nih.gov/pubmed/31994716", "http://www.ncbi.nlm.nih.gov/pubmed/30847674", "http://www.ncbi.nlm.nih.gov/pubmed/33275677", "http://www.ncbi.nlm.nih.gov/pubmed/30726693", "http://www.ncbi.nlm.nih.gov/pubmed/33139979" ], "ideal_answer": [ "Givosiran is an aminolevulinate synthase 1 (ALAS1)-directed small interfering RNA (siRNA) covalently linked to a ligand to enable specific delivery of the siRNA to hepatocytes. This results in downregulation of ALAS1 mRNA and prevents accumulation of neurotoxic \u03b4-aminolevulinic acid and porphobilinogen levels that are associated with acute porphyria attacks." ], "type": "summary", "id": "602494cf1cb411341a00009c", "snippets": [ { "offsetInBeginSection": 527, "offsetInEndSection": 760, "text": "Givosiran acts as a conventional siRNA to trigger RNA interference (RNAi)-mediated gene silencing on delta-ALA synthase 1 (ALAS1), thus returning ALA and PBG metabolites to the physiological level to attenuate further neurotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Givosiran is a small interfering ribonucleic acid agent that was recently approved in the United States for the treatment of acute hepatic porphyria (AHP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31994716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 373, "text": "Givosiran (Givlaari\u2122) is an aminolevulinate synthase 1 (ALAS1)-directed small interfering RNA (siRNA) covalently linked to a ligand to enable specific delivery of the siRNA to hepatocytes. This results in downregulation of ALAS1 mRNA and prevents accumulation of neurotoxic \u03b4-aminolevulinic acid and porphobilinogen levels that are associated with acute porphyria attacks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32034693", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 330, "text": "Givosiran, an RNA interference therapy, inhibits ALAS1 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32521132", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 784, "text": "A number of RNA drugs have been approved for medical use, including aptamers (e.g., pegaptanib) that mechanistically act on protein target and small interfering RNAs (e.g., patisiran and givosiran) and antisense oligonucleotides (e.g., inotersen and golodirsen) that directly interfere with RNA targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32929000", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 390, "text": "Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30726693", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 459, "text": "After a two-decade journey from its discovery, two approvals of siRNA therapeutics, ONPATTRO\u00ae (patisiran) and GIVLAARI\u2122 (givosiran), have been achieved by Alnylam Pharmaceuticals. Reviewing the long-te", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32561705", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1308, "text": "Givosiran, another RNAi therapeutic, targeting 5-aminolevulinic acid synthase, has been positively tested in acute intermittent porphyria in phase 1/2 and ongoing phase 3 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30847674", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 801, "text": " of RNA drugs have been approved for medical use, including aptamers (e.g., pegaptanib) that mechanistically act on protein target and small interfering RNAs (e.g., patisiran and givosiran) and antisense oligonucleotides (e.g., inotersen and golodirsen) that directly interfere with RNA targets. Furthermore, gui", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32929000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "In November 2019 givosiran became the second small interfering RNA (siRNA)-based drug to receive US Food and Drug Administration (FDA) approval, it has been developed for the treatment of acute intermittent porphyria (AIP), a disorder characterized by life-threatening acute neurovisceral attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 759, "text": "Givosiran acts as a conventional siRNA to trigger RNA interference (RNAi)-mediated gene silencing on delta-ALA synthase 1 (ALAS1), thus returning ALA and PBG metabolites to the physiological level to attenuate further neurotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Givosiran (Givlaari\u2122) is an aminolevulinate synthase 1 (ALAS1)-directed small interfering RNA (siRNA) covalently linked to a ligand to enable specific delivery of the siRNA to hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32034693", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 466, "text": "osynthesis. Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.METHODS: We conducted a phase 1 trial of givosiran in patients with acute in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30726693", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 556, "text": " porphyria. Givosiran, an RNA interference therapy, inhibits ALAS1 expression.METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned symptomatic patients with acute hepatic porphyria to receive either subcutaneous givosiran (2.5 mg per kilogram of body weight) or placebo ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32521132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "State-of-the-art small interfering RNA (siRNA) therapeutics such as givosiran and fitusiran are constructed from three variable components: a fully-modified RNA core that conveys metabolic stability, a targeting moiety that mediates target-cell uptake, and a linker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32311310", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 937, "text": "New treatment options include givosiran (siRNA) to down-regulate ALA synthase-1 (ALAS1) and the messenger RNA of PBGD (PBGD mRNA) delivered to the liver cells of patients with AIP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33139979", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 838, "text": "Management of AIP includes awareness and avoidance of triggering factors, infusions of hemin for severe acute attacks, and, if indicated for chronic suppressive therapy, maintenance treatment with hemin or givosiran, a small interfering RNA molecule that antagonizes ALA synthase 1 transcripts. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33275677", "endSection": "abstract" } ] }, { "body": "Is Olaparib effective for prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33012578", "http://www.ncbi.nlm.nih.gov/pubmed/29880291", "http://www.ncbi.nlm.nih.gov/pubmed/33044685", "http://www.ncbi.nlm.nih.gov/pubmed/24789362", "http://www.ncbi.nlm.nih.gov/pubmed/24225019", "http://www.ncbi.nlm.nih.gov/pubmed/32343890", "http://www.ncbi.nlm.nih.gov/pubmed/28895177", "http://www.ncbi.nlm.nih.gov/pubmed/27317574", "http://www.ncbi.nlm.nih.gov/pubmed/26658963", "http://www.ncbi.nlm.nih.gov/pubmed/32955174", "http://www.ncbi.nlm.nih.gov/pubmed/31075528", "http://www.ncbi.nlm.nih.gov/pubmed/31404966", "http://www.ncbi.nlm.nih.gov/pubmed/32293692", "http://www.ncbi.nlm.nih.gov/pubmed/31501807", "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "http://www.ncbi.nlm.nih.gov/pubmed/25616434", "http://www.ncbi.nlm.nih.gov/pubmed/32814685", "http://www.ncbi.nlm.nih.gov/pubmed/25583815", "http://www.ncbi.nlm.nih.gov/pubmed/32982407", "http://www.ncbi.nlm.nih.gov/pubmed/29465803", "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "http://www.ncbi.nlm.nih.gov/pubmed/31806540", "http://www.ncbi.nlm.nih.gov/pubmed/23847380", "http://www.ncbi.nlm.nih.gov/pubmed/29979319", "http://www.ncbi.nlm.nih.gov/pubmed/28069876", "http://www.ncbi.nlm.nih.gov/pubmed/28280302", "http://www.ncbi.nlm.nih.gov/pubmed/30514390" ], "triples": [ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0106149", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0090893", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0106148", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0091054", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0290426", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0290427", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0290428", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0290425", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7786660", "o": "D011471" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0667486", "o": "D011471" } ], "ideal_answer": [ "Yes, olaparib was shown to be effective for treatment of prostate cancer. Olaparib led to stable disease or tumor regressions of prostate cancer patients.", "Yes. Olaparib has antitumour activity against metastatic castration-resistant prostate cancer with DDR gene aberrations.", "Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate." ], "exact_answer": "yes", "concepts": [ "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011471", "http://www.disease-ontology.org/api/metadata/DOID:10286" ], "type": "yesno", "id": "602498cb1cb411341a00009e", "snippets": [ { "offsetInBeginSection": 122, "offsetInEndSection": 496, "text": "We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract" }, { "offsetInBeginSection": 2035, "offsetInEndSection": 2244, "text": "CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 768, "text": " In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "In a phase II study, researchers found that the PARP inhibitor olaparib led to stable disease or tumor regressions in patients with advanced breast, ovarian, pancreatic, and prostate cancers who had germline mutations in BRCA1 or BRCA2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583815", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 647, "text": "Eligibility included ovarian cancer resistant to prior platinum; breast cancer with \u2265 three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 1427, "text": "The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease \u2265 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 1301, "text": "It is increasingly clear that there are molecularly distinct subtypes of various common cancers, with different therapeutic approaches required for each subtype, for example, the use of the monoclonal antibodies (trastuzumab and cetuximab) in HER2-positive breast cancer and wild-type KRAS colorectal cancer; tyrosine kinase inhibitors (imatinib, gefitinib, erlotinib and crizotinib) in chronic myeloid leukaemia, gastrointestinal stromal tumours and non-small-cell lung cancer and intracellular agents (vemurafenib and olaparib) in metastatic malignant melanoma and ovarian, breast and prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789362", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 703, "text": "Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2(MUT+) and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225019", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 828, "text": "Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index<0.9), whereas normal prostatic cells did not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "endSection": "abstract" }, { "offsetInBeginSection": 2035, "offsetInEndSection": 2243, "text": "CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 704, "text": "Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2(MUT+) and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225019", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "title" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1093, "text": "Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index < 0.9), whereas normal prostatic cells did not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 501, "text": "We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "A phase II study of the PARP inhibitor olaparib (AstraZeneca) for cancer patients with inherited BRCA1 and BRCA2 gene mutations confirmed earlier results showing clinical benefit for advanced breast and ovarian cancers, and demonstrated evidence of effectiveness against pancreatic and prostate cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23847380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 496, "text": "BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1646, "text": "Silencing RAD51 sensitized prostate cancer cells to SAHA and olaparib alone. Collectively, cotreatment with HDACi and PARPi downregulated HR-related protein expression and concomitantly increased DNA damage, resulting in prostate cancer cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 829, "text": "Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index<0.9), whereas normal prostatic cells did not. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "endSection": "abstract" }, { "offsetInBeginSection": 1809, "offsetInEndSection": 2244, "text": "The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 822, "text": "Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index < 0.9), whereas normal prostatic cells did not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 768, "text": "In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616434", "endSection": "abstract" }, { "offsetInBeginSection": 3329, "offsetInEndSection": 3589, "text": "INTERPRETATION: Olaparib has antitumour activity against metastatic castration-resistant prostate cancer with DDR gene aberrations, supporting the implementation of genomic stratification of metastatic castration-resistant prostate cancer in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31806540", "endSection": "abstract" }, { "offsetInBeginSection": 1966, "offsetInEndSection": 2358, "text": "CONCLUSIONS: In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32343890", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 622, "text": "Olaparib is an additional option for second- and third-line treatment in those with alterations in BRCA1, BRCA2, and ATM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32293692", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1319, "text": "In this review, we describe current therapies for mCRPC, the rationale for anti-PARP therapies, the pharmacology of olaparib for prostate cancer, clinical trials of olaparib for mCRPC, our clinical experience with olaparib for prostate cancer at a comprehensive cancer center, and future directions of olaparib for the treatment of mCRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28895177", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 571, "text": "Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30514390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30514390", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "BACKGROUND: Patients with metastatic castration-resistant prostate cancer and homologous recombination repair (HRR) mutations have a better response to treatment with the poly(ADP-ribose) polymerase inhibitor olaparib than patients without HRR mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29880291", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 339, "text": "The TOPARP-A clinical trial demonstrated that the PARP inhibitor olaparib may be an effective strategy for treating prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31075528", "endSection": "abstract" }, { "offsetInBeginSection": 2299, "offsetInEndSection": 2488, "text": "MMARY: The poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib are now approved by the Food and Drug Administration for the treatment of advanced prostate cancer. Here, we ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32814685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "BACKGROUND: We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease had progressed during previous treatment with a next-generation hormonal agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955174", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 352, "text": "Recent clinical studies show favorable results for the PARP inhibitor olaparib used as single agent for treatment of metastatic castration-resistant PCa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29465803", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1174, "text": "The PROFOUND phase III trial, comparing olaparib with enzalutamide/abiraterone therapy, revealed increased radiological progression-free survival (rPFS) and overall survival (OS) among patients with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1, BRCA2 or ATM mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33044685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Olaparib Targets Some Advanced Prostate Cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26658963", "endSection": "title" }, { "offsetInBeginSection": 65, "offsetInEndSection": 255, "text": "The PARP inhibitor (PARPi) olaparib received FDA breakthrough designation for treatment of metastatic castration-resistant prostate cancers (CRPC) carrying mutations in BRCA1/2 or ATM genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31501807", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 617, "text": " In prostate cancer, two PARPi, rucaparib and olaparib, have been FDA approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Olaparib is an FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28069876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Targeting Plk1 to Enhance Efficacy of Olaparib in Castration-Resistant Prostate Cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28069876", "endSection": "title" }, { "offsetInBeginSection": 473, "offsetInEndSection": 649, "text": "RECENT FINDINGS: The approval of several PARPi (olaparib, rucaparib, and niraparib) has driven the focus of anticancer treatment on synthetic lethality in prostate cancer too. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29979319", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1111, "text": "PATIENT SUMMARY: A large clinical study concluded that treatment with the PARP inhibitor olaparib benefits men with metastatic castration-resistant prostate cancer whose tumors harbor alterations in 15 different DNA repair genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33012578", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 853, "text": " Among them, olaparib and rucaparib have breakthrough designations for BRCA1/2-mutated mCRPC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31404966", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 785, "text": "In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28280302", "endSection": "abstract" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1547, "text": "Of note is the recent U.S. Food and Drug Administration breakthrough therapy designation of olaparib for the treatment of BRCA1/2- or ATM-mutated metastatic castration-resistant prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27317574", "endSection": "abstract" } ] }, { "body": "What is Corkscrew Esophagus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29733830", "http://www.ncbi.nlm.nih.gov/pubmed/15828301", "http://www.ncbi.nlm.nih.gov/pubmed/27832322", "http://www.ncbi.nlm.nih.gov/pubmed/1736462", "http://www.ncbi.nlm.nih.gov/pubmed/9705572", "http://www.ncbi.nlm.nih.gov/pubmed/1992626" ], "ideal_answer": [ "Corkscrew esophagus is a classic finding of diffuse esophageal spasm in barium studies reflecting abnormal contractions, leading to compartmentalization and curling of the esophagus, ultimately giving an appearance similar to a corkscrew or rosary beads." ], "type": "summary", "id": "6024a5891cb411341a0000a3", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "Corkscrew esophagus (also referred as rosary bead esophagus) is a classic finding of diffuse esophageal spasm (DES) in barium studies reflecting abnormal contractions, leading to compartmentalization and curling of the esophagus, ultimately giving an appearance similar to a corkscrew or rosary beads. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27832322", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 490, "text": "Esophagography evidenced a disorder of esophagus motility with diffuse multiple spasm, reminiscent of the 'corkscrew esophagus'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9705572", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 264, "text": "Corkscrew oesophagus is a radiological diagnosis and is characterised by twisted segments in the distal third of the oesophagus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1736462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Nonpropulsive esophageal contractions radiologically described as tertiary contractions or \"corkscrew\" esophagus suggest the presence of an underlying motility disorder and may lead to impaired acid clearance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1992626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Corkscrew esophagus (also referred as rosary bead esophagus) is a classic finding of diffuse esophageal spasm (DES) in barium studies reflecting abnormal contractions, leading to compartmentalization and curling of the esophagus, ultimately giving an appearance similar to a corkscrew or rosary beads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27832322", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 489, "text": "Esophagography evidenced a disorder of esophagus motility with diffuse multiple spasm, reminiscent of the 'corkscrew esophagus'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9705572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Corkscrew esophagus (also referred as rosary bead esophagus) is a classic finding of diffuse esophageal spasm (DES) in barium studies reflecting abnormal contractions, leading to compartmentalization and curling of the esophagus, ultimately giving an appearance similar to a corkscrew or rosary beads. We r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27832322", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 296, "text": "Barium swallow examination revealed the esophagus to have the corkscrew appearance characteristic of diffuse esophageal spasm (DES). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15828301", "endSection": "abstract" } ] }, { "body": "List 3 conventional synthetic DMARDs.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29231235", "http://www.ncbi.nlm.nih.gov/pubmed/24072562", "http://www.ncbi.nlm.nih.gov/pubmed/31969328" ], "ideal_answer": [ "Three conventional synthetic (cs) DMARDs include methotrexate (MTX), leflunomide, and sulfasalazine." ], "exact_answer": [ [ "methotrexate" ], [ "leflunomide" ], [ "sulfasalazine" ] ], "type": "list", "id": "6025a1e91cb411341a0000b4", "snippets": [ { "offsetInBeginSection": 730, "offsetInEndSection": 1251, "text": "The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31969328", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 1250, "text": "RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31969328", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 762, "text": "Conventional synthetic DMARDs such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine appear to be safe during the perioperative period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29231235", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1178, "text": "tsDMARDs would then constitute only those that were specifically developed to target a particular molecular structure (such as tofacitinib, fostamatinib, baricitinib or apremilast, or agents not focused primarily on rheumatic diseases, such as imatinib or ibrutinib), while csDMARDs would comprise the traditional drugs (such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, gold salts and others).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24072562", "endSection": "abstract" } ] }, { "body": "Is isradipine effective for Parkinson's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32227247" ], "ideal_answer": [ "No. Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage Parkinson's disease." ], "exact_answer": "no", "type": "yesno", "id": "6025fd261cb411341a0000bf", "snippets": [ { "offsetInBeginSection": 1255, "offsetInEndSection": 1569, "text": "Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P\u00a0= 0.85).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227247", "endSection": "abstract" }, { "offsetInBeginSection": 1924, "offsetInEndSection": 2046, "text": "Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227247", "endSection": "abstract" } ] }, { "body": "Is MK-1602 a CGRP antagonist?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27269043" ], "ideal_answer": [ "Yes, MK-1602 is a CGRP antagonist." ], "exact_answer": "yes", "type": "yesno", "id": "6026c1071cb411341a0000cb", "snippets": [ { "offsetInBeginSection": 5, "offsetInEndSection": 199, "text": "The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1553, "text": "This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" } ] }, { "body": "Which company developed eptinezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32266704" ], "ideal_answer": [ "Eptinezumab was developed by Lundbeck Seattle BioPharmaceuticals." ], "exact_answer": [ "Lundbeck Seattle BioPharmaceuticals" ], "type": "factoid", "id": "6026ef311cb411341a0000d4", "snippets": [ { "offsetInBeginSection": 267, "offsetInEndSection": 415, "text": "Eptinezumab, delivered by intravenous (IV) administration, is being developed by Lundbeck Seattle BioPharmaceuticals for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32266704", "endSection": "abstract" } ] }, { "body": "What are the features of the AESOP syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31119772", "http://www.ncbi.nlm.nih.gov/pubmed/23198009", "http://www.ncbi.nlm.nih.gov/pubmed/23473278", "http://www.ncbi.nlm.nih.gov/pubmed/27531391", "http://www.ncbi.nlm.nih.gov/pubmed/12544710" ], "ideal_answer": [ "Adenopathy and Extensive Skin Patch Overlying a Plasmacytoma is defined as the AESOP Syndrome." ], "exact_answer": [ [ "Adenopathy" ], [ "Extensive Skin Patch Overlying a Plasmacytoma" ] ], "type": "list", "id": "602748681cb411341a0000e1", "snippets": [ { "offsetInBeginSection": 350, "offsetInEndSection": 585, "text": "Further workup revealed a monoclonal gammopathy, an osteolytic chest wall plasmacytoma underlying the plaque, and regional lymphadenopathy leading to a diagnosis of adenopathy and extensive skin patch overlying a plasmacytoma (AESOP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31119772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin signs) and AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) syndromes are rare paraneoplastic conditions due to an underlying plasma cell dyscrasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27531391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Adenopathy and extensive skin patch overlying a plasmacytoma (AESOP) syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473278", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "In our manuscript we describe the cutaneous manifestations of a rare condition termed Adenopathy and Extensive Skin Patch Overlying Plasmacytoma (AESOP) syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Adenopathy and Extensive Skin Patch Overlying a Plasmacytoma (AESOP) Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23198009", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin signs) and AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) syndromes are rare paraneoplastic conditions due to an underlying plasma cell dyscrasia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27531391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) syndrome: report of 4 cases of a new syndrome revealing POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome at a curable stage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12544710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "In our manuscript we describe the cutaneous manifestations of a rare condition termed Adenopathy and Extensive Skin Patch Overlying Plasmacytoma (AESOP) syndrome. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23473278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin signs) and AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) syndromes are rare paraneoplastic conditions due to an underlying plasma cell dyscrasia. We repor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27531391", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 594, "text": "er workup revealed a monoclonal gammopathy, an osteolytic chest wall plasmacytoma underlying the plaque, and regional lymphadenopathy leading to a diagnosis of adenopathy and extensive skin patch overlying a plasmacytoma (AESOP). Biopsy of", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31119772", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 584, "text": "Further workup revealed a monoclonal gammopathy, an osteolytic chest wall plasmacytoma underlying the plaque, and regional lymphadenopathy leading to a diagnosis of adenopathy and extensive skin patch overlying a plasmacytoma (AESOP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31119772", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the VIFUP regimen for breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14504046", "http://www.ncbi.nlm.nih.gov/pubmed/11249057", "http://www.ncbi.nlm.nih.gov/pubmed/11911307", "http://www.ncbi.nlm.nih.gov/pubmed/18595702", "http://www.ncbi.nlm.nih.gov/pubmed/12239445" ], "ideal_answer": [ "ViFuP includes vinorelbine, cisplatin and continuous infusion of 5-fluorouracil." ], "exact_answer": [ [ "vinorelbine" ], [ "cisplatin" ], [ "5-fluorouracil" ] ], "type": "list", "id": "602752681cb411341a0000e7", "snippets": [ { "offsetInBeginSection": 641, "offsetInEndSection": 986, "text": "PATIENTS AND METHODS: Breast cancer patients, clinical stages T2-T3, N0-N2, M0, and Ki-67 labelling index >/= 20%, were treated every 3 weeks with a maximum of six courses of vinorelbine 20 mg total dose intravenously (i.v.) on days 1 and 3, cisplatin 60 mg/ m(2) i.v. on day 1 and 5-FU 200 mg/m(2)/day as a continuous infusion (ViFuP regimen). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14504046", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 575, "text": "METHODS: 25 patients with locally advanced head and neck cancer were treated with 4 cycles of vinorelbine (20 mg i.v. day 1, 3), cisplatin (60 mg/m(2) i.v. day 1) and 5-fluorouracil (200 mg/m(2) continuous i.v. infusion day 1-21) (ViFuP regimen) followed by bifractionated radiotherapy (bidRT) up to 74.4 Gy in 62 fractions of 1.2 Gy twice daily.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12239445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Vinorelbine, cisplatin and continuous infusion of 5-fluorouracil (ViFuP) in metastatic breast cancer patients: a phase II study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11249057", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 551, "text": "We assessed efficacy in terms of response rate and time to progression of a combination with continuous infusion 5-fluorouracil (5-FU), vinorelbine and cisplatin (ViFuP regimen), as a first or subsequent line treatment for metastatic breast cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11249057", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 407, "text": "The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11911307", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 557, "text": "Patients with large operable (cT2-T3, N0-2, M0), ER > or =10% breast cancer were treated in two consecutive studies with preoperative chemotherapy (Study I: six courses of either fluorouracil, leucovorin, vinorelbine (FLN), or vinorelbine, cisplatin, and continuous infusion of fluorouracil (ViFuP), at the discretion of the treating physician; Study II: capecitabine and oral vinorelbine (CAVINO)). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18595702", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 406, "text": "The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11911307", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 556, "text": "Patients with large operable (cT2-T3, N0-2, M0), ER > or =10% breast cancer were treated in two consecutive studies with preoperative chemotherapy (Study I: six courses of either fluorouracil, leucovorin, vinorelbine (FLN), or vinorelbine, cisplatin, and continuous infusion of fluorouracil (ViFuP), at the discretion of the treating physician; Study II: capecitabine and oral vinorelbine (CAVINO)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18595702", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 415, "text": "e feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. Twenty-s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11911307", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 552, "text": "We assessed efficacy in terms of response rate and time to progression of a combination with continuous infusion 5-fluorouracil (5-FU), vinorelbine and cisplatin (ViFuP regimen), as a first or subsequent line treatment for metastatic breast cancer patients.P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11249057", "endSection": "abstract" }, { "offsetInBeginSection": 285, "offsetInEndSection": 814, "text": "uitable. We assessed efficacy in terms of response rate and time to progression of a combination with continuous infusion 5-fluorouracil (5-FU), vinorelbine and cisplatin (ViFuP regimen), as a first or subsequent line treatment for metastatic breast cancer patients.PATIENTS AND METHODS: One hundred consecutive patients with advanced breast cancer were treated with 5-FU 200 mg/m2 administered continuously through a permanent central venous line; vinorelbine was given on days 1 and 3 at a dose of 20 mg and cisplatin was admin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11249057", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the EE-4A regimen for Wilm's tumor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18970928", "http://www.ncbi.nlm.nih.gov/pubmed/30774381" ], "ideal_answer": [ "EE-4A regimen includes dactinomycin and vincristine." ], "exact_answer": [ [ "dactinomycin" ], [ "vincristine" ] ], "type": "list", "id": "602753951cb411341a0000e9", "snippets": [ { "offsetInBeginSection": 1725, "offsetInEndSection": 1803, "text": "Five patients received treatment regimen EE-4A, dactinomycin, and vincristine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18970928", "endSection": "abstract" }, { "offsetInBeginSection": 622, "offsetInEndSection": 735, "text": "One month following the resection, chemotherapy with vincristine plus dactinomycin (EE-4A regimen) was commenced.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30774381", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 749, "text": "llowing the resection, chemotherapy with vincristine plus dactinomycin (EE-4A regimen) was commenced. At the 69-mon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30774381", "endSection": "abstract" } ] }, { "body": "Does inactivation of CYLD help in colorectal cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27042826" ], "ideal_answer": [ "\u039d\u03bf. Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis." ], "exact_answer": "no", "type": "yesno", "id": "6027dc011cb411341a0000eb", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27042826", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1773, "text": "CYLD is a tumor suppressor that has been linked to the development of various human malignancies, including colon cancer. The tumor-suppressing function of CYLD is associated with its deubiquitinating activity, which maps to the carboxyl-terminal region of the protein. In the present study we evaluated the role of intestinal epithelial CYLD in colitis-associated cancer using a conditional mouse CYLD inactivation model.METHODS: In order to evaluate the role of CYLD in intestinal epithelial carcinogenesis, mice (IEC-Cyld (\u03949) mice) that carry a mutation that eliminates the deubiquitinating domain of CYLD in intestinal epithelial cells (IEC) were generated by crossing Villin-Cre transgenic mice to previously generated mice carrying a loxP-flanked Cyld exon 9 (Cyld (flx9) mice).RESULTS: We found that IEC-Cyld (\u03949) mice did not present spontaneous intestinal abnormalities up to one year of age. However, upon challenge with a combination of genotoxic (AOM) and pro-inflammatory (DSS) agents we found that the number of adenomas in the IEC-Cyld (\u03949) mice was dramatically increased compared to the control mice. Inactivation of CYLD in intestinal epithelial cells did not affect the classical nuclear factor-kappaB (NF-\u03baB) and c-Jun kinase (JNK) activation pathways under physiological conditions, suggesting that these pathways do not predispose CYLD-deficient intestinal epithelia to colorectal cancer development before the onset of genotoxic and/or pro-inflammatory stress.CONCLUSIONS: Our findings underscore a critical tumor-suppressing role for functional intestinal epithelial CYLD in colitis-associated carcinogenesis. CYLD expression and its associated pathways in intestinal tumors may be exploited for future prognostic and therapeutic purposes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27042826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27042826", "endSection": "title" } ] }, { "body": "Which network analysis method can you use for prioritization of metabolic disease genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32637154" ], "ideal_answer": [ "metPropagate is a network-guided propagation of metabolomic information for prioritization of metabolic disease genes. metPropagate was able to prioritize at least one causative gene in the top 20th percentile of candidate genes for 92% of patients with known IEMs.", "Many inborn errors of metabolism (IEMs) are amenable to treatment, therefore early diagnosis is imperative. Whole-exome sequencing (WES) variant prioritization coupled with phenotype-guided clinical and bioinformatics expertise is typically used to identify disease-causing variants; however, it can be challenging to identify the causal candidate gene when a large number of rare and potentially pathogenic variants are detected. MetPropagate is a network-based approach that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs.", "MetPropagate is a network-guided propagation of metabolomic information for prioritization of metabolic disease genes. Basically, you take a single patient and a group of controls, and compare their metabolomic data to the data of other patients with IEMs. If you find a gene that is in the top 20% of the population, you rank it higher in the network. If not, you don't rank it at all.", "Met Propagate is a network-based approach that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs.", "MetPropagate is a network-guided propagation of metabolomic information for prioritization of metabolic disease genes. Basically, you take a single patient and a group of controls, and compare their metabolomic data to the data of other patients with IEMs. If you find a gene that is in the top 20% of the population, you rank it higher than the other genes in the population. If not, you don't." ], "exact_answer": [ "metPropagate" ], "type": "factoid", "id": "6027f8ae1cb411341a0000ed", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "metPropagate: network-guided propagation of metabolomic information for prioritization of metabolic disease genes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1690, "text": "Many inborn errors of metabolism (IEMs) are amenable to treatment, therefore early diagnosis is imperative. Whole-exome sequencing (WES) variant prioritization coupled with phenotype-guided clinical and bioinformatics expertise is typically used to identify disease-causing variants; however, it can be challenging to identify the causal candidate gene when a large number of rare and potentially pathogenic variants are detected. Here, we present a network-based approach, metPropagate, that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs. We validate metPropagate on 107 patients with IEMs diagnosed in Miller et al. (2015) and 11 patients with both CNS and metabolic abnormalities. The metPropagate method ranks candidate genes by label propagation, a graph-smoothing algorithm that considers each gene's metabolic perturbation in addition to the network of interactions between neighbors. metPropagate was able to prioritize at least one causative gene in the top 20th percentile of candidate genes for 92% of patients with known IEMs. Applied to patients with suspected neurometabolic disease, metPropagate placed at least one causative gene in the top 20th percentile in 9/11 patients, and ranked the causative gene more highly than Exomiser's phenotype-based ranking in 6/11 patients. Interestingly, ranking by a weighted combination of metPropagate and Exomiser scores resulted in improved prioritization. The results of this study indicate that network-based analysis of UM data can provide an additional mode of evidence to prioritize causal genes in patients with suspected IEMs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 992, "text": "The metPropagate method ranks candidate genes by label propagation, a graph-smoothing algorithm that considers each gene's metabolic perturbation in addition to the network of interactions between neighbors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 650, "text": "we present a network-based approach, metPropagate, that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs. We valida", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "metPropagate: network-guided propagation of metabolomic information for prioritization of metabolic disease genes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "title" }, { "offsetInBeginSection": 431, "offsetInEndSection": 640, "text": "Here, we present a network-based approach, metPropagate, that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1391, "text": "Applied to patients with suspected neurometabolic disease, metPropagate placed at least one causative gene in the top 20th percentile in 9/11 patients, and ranked the causative gene more highly than Exomiser's phenotype-based ranking in 6/11 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1139, "text": "metPropagate was able to prioritize at least one causative gene in the top 20th percentile of candidate genes for 92% of patients with known IEMs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "abstract" }, { "offsetInBeginSection": 1392, "offsetInEndSection": 1513, "text": "Interestingly, ranking by a weighted combination of metPropagate and Exomiser scores resulted in improved prioritization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637154", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the IROX regimen for colorectal cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17687151", "http://www.ncbi.nlm.nih.gov/pubmed/20530282", "http://www.ncbi.nlm.nih.gov/pubmed/25349295", "http://www.ncbi.nlm.nih.gov/pubmed/18824706", "http://www.ncbi.nlm.nih.gov/pubmed/19822515", "http://www.ncbi.nlm.nih.gov/pubmed/14665611", "http://www.ncbi.nlm.nih.gov/pubmed/29211295", "http://www.ncbi.nlm.nih.gov/pubmed/17901952", "http://www.ncbi.nlm.nih.gov/pubmed/29246011", "http://www.ncbi.nlm.nih.gov/pubmed/17559146", "http://www.ncbi.nlm.nih.gov/pubmed/19390546", "http://www.ncbi.nlm.nih.gov/pubmed/19001325", "http://www.ncbi.nlm.nih.gov/pubmed/15677624", "http://www.ncbi.nlm.nih.gov/pubmed/19444385" ], "ideal_answer": [ "IROX regimen for colorectal cancer includes irinotecan and oxaliplatin." ], "exact_answer": [ [ "irinotecan" ], [ "oxaliplatin" ] ], "type": "list", "id": "602823e61cb411341a0000f9", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "BACKGROUND: The authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS-L) expression would have a higher response rate to combined 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS-H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS-H tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29211295", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 571, "text": "The 10 regimens included folinic acid + 5-fluorouracil + oxaliplatin (FOLFOX), folinic acid + 5-fluorouracil + irinotecan (FOLFIRI), folinic acid + 5-fluorouracil + gemcitabine (FFG), folinic acid + 5-fluorouracil + trimetrexate (FFT), folinic acid + 5-fluorouracil (FF), irinotecan + oxaliplatin (IROX), raltitrexed + oxaliplatin (TOMOX), folinic acid + tegafur-uracil (FTU), raltitrexed, and capecitabine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29246011", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 534, "text": "We simulated phase II trials by resampling patients from N9741, a randomized phase III trial of chemotherapy regimens for metastatic colorectal cancer, and compared the power of various end points to detect the superior therapy (FOLFOX [infusional fluorouracil, leucovorin, and oxaliplatin] had longer overall survival than both IROX [irinotecan plus oxaliplatin] and IFL [irinotecan and bolus fluorouracil plus leucovorin]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25349295", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 669, "text": "PATIENTS AND METHODS: Germline DNA was extracted from 520 patients on the North American Gastrointestinal Intergroup N9741 study. Three study arms were evaluated: IFL (fluorouracil [FU] + irinotecan [IRN]), FOLFOX (FU + oxaliplatin), and IROX (IRN + oxaliplatin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20530282", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1327, "text": "The patient had progression of disease on IROX (irinotecan/oxaliplatin) and irinotecan/cetuximab regimens. He was started on gemcitabine/capecitabine and developed HFS again, which was controlled with aggressive skin care and vitamin B6 treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19822515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Haller et al. demonstrated that irinotecan plus oxaliplatin (IROX) is more efficacious than irinotecan alone after fluoropyrimidine failure in advanced colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19390546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "UNLABELLED: PURPOSE To determine whether irinotecan plus oxaliplatin (IROX) is superior to irinotecan alone in patients with metastatic colorectal cancer (CRC) previously treated with single-agent fluoropyrimidines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824706", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 570, "text": "The 10 regimens included folinic acid + 5-fluorouracil + oxaliplatin (FOLFOX), folinic acid + 5-fluorouracil + irinotecan (FOLFIRI), folinic acid + 5-fluorouracil + gemcitabine (FFG), folinic acid + 5-fluorouracil + trimetrexate (FFT), folinic acid + 5-fluorouracil (FF), irinotecan + oxaliplatin (IROX), raltitrexed + oxaliplatin (TOMOX), folinic acid + tegafur-uracil (FTU), raltitrexed, and capecitabine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29246011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17559146", "endSection": "title" }, { "offsetInBeginSection": 284, "offsetInEndSection": 480, "text": "We attempted to evaluate the efficacy and safety of a combination of irinotecan and oxaliplatin (IROX) as a salvage treatment for patients with gemcitabine- and 5-FU- refractory pancreatic cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19444385", "endSection": "abstract" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1219, "text": "isease on IROX (irinotecan/oxaliplatin) and irinotecan/cetuximab regimens. He was started on gemcitabine/ca", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19822515", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 1040, "text": "RESULTS: The observed 5-year survival with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) of 9.8% was better than with irinotecan plus bolus fluorouracil and leucovorin (IFL; 3.7%; P = .04) or with bolus irinotecan/oxaliplatin (IROX; 5.1%; P = .128).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19001325", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 270, "text": "We evaluated the irinotecan-oxaliplatin combination (IROX regimen) in previously untreated patients with non-favorable subsets of unknown primary carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17901952", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 613, "text": "PATIENTS AND METHODS: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14665611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Pilot study of irinotecan/oxalipltin (IROX) combination chemotherapy for patients with gemcitabine- and 5-fluorouracil- refractory pancreatic cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19444385", "endSection": "title" }, { "offsetInBeginSection": 617, "offsetInEndSection": 747, "text": " The three treatment arms consist of IFL (irinotecan + FU/LV), FOLFOX4 (oxaliplatin + FU/LV), and IROX (irinotecan + oxaliplatin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17687151", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 670, "text": "PATIENTS AND METHODS: Patient research records in study arms (A) irinotecan/5-FU/leucovorin (LV) (IFL, n = 264), (F) oxaliplatin/5-FU/LV (FOLFOX4, n = 267) and (G) oxaliplatin/irinotecan (IROX, n = 265) were reviewed. TTP and median OS were calculated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15677624", "endSection": "abstract" } ] }, { "body": "What are the targets of pemigatinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32203698", "http://www.ncbi.nlm.nih.gov/pubmed/32315352", "http://www.ncbi.nlm.nih.gov/pubmed/32684989", "http://www.ncbi.nlm.nih.gov/pubmed/32472305", "http://www.ncbi.nlm.nih.gov/pubmed/32677452" ], "ideal_answer": [ "Pemigatinib is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) 1, FGFR2 and FGFR3, received accelerated approval for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or other rearrangement, as detected by a US FDA-approved test." ], "exact_answer": [ [ "FGFR 1" ], [ "FGFR2" ], [ "FGFR3" ] ], "type": "list", "id": "602826da1cb411341a0000fb", "snippets": [ { "offsetInBeginSection": 128, "offsetInEndSection": 198, "text": "Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32203698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Pemigatinib (PEMAZYRE\u2122), a small molecule inhibitor of fibroblast growth factor receptor (FGFR) 1, FGFR2 and FGFR3, received accelerated approval in April 2020 in the USA for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or other rearrangement, as detected by a US FDA-approved test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32472305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32315352", "endSection": "title" }, { "offsetInBeginSection": 307, "offsetInEndSection": 498, "text": "Here, we present the molecular structure and preclinical characterization of INCB054828 (pemigatinib), a novel, selective inhibitor of FGFR 1, 2, and 3, currently in phase 2 clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32315352", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 387, "text": "Pemigatinib, a selective, potent, oral inhibitor of FGFR1-3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring FGFR2 fusions/rearrangements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32677452", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 757, "text": "Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32684989", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 508, "text": " we present the molecular structure and preclinical characterization of INCB054828 (pemigatinib), a novel, selective inhibitor of FGFR 1, 2, and 3, currently in phase 2 clinical trials. INCB054828", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32315352", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 986, "text": "is disease. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3.Methods: The FiGhTeR trial is a phase II, single-arm, open-label study to assess safety and activity of the FGFR inhibitor pemigatinib as second-line treatment strategy in metastatic EGJ/GC patients progressing under trastuzumab-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32684989", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 497, "text": "Here, we present the molecular structure and preclinical characterization of INCB054828 (pemigatinib), a novel, selective inhibitor of FGFR 1, 2, and 3, currently in phase 2 clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32315352", "endSection": "abstract" } ] }, { "body": "Is there high nucleotide diversity in the Drosophila suzukii species?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25158796" ], "ideal_answer": [ "Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. There are high levels of nucleotide diversity in this species and research suggests that the recent invasions of Europe and the continental United States are independent demographic events.", "Yes, there is high nucleotide diversity in the Drosophila suzukii species. There is a lot of genetic diversity in this species, and it is thought that the recent expansion of the species into Europe and the continental United States are independent demographic events. This means that there is a high level of diversity within the species.", "Yes, there is high nucleotide diversity in the Drosophila suzukii species. There is a lot of genetic diversity in this species, and it is thought that the recent expansion of the species into Europe and the Americas are independent demographic events.", "Yes. There is high nucleotide diversity within the Drosophila suzukii species.", "Yes. There is high nucleotide diversity within and between populations of Drosophila suzukii, as shown by the presence of 12.1% single-nucleotide variants and 43.6% double-stranded DNA.", "Yes. There is high nucleotide diversity within and between populations of Drosophila suzukii, across all developmental stages examined from only one genome.", "Yes. There is high nucleotide diversity within and between populations of Drosophila suzukii, manifesting both in gene expression patterns and genomic locations." ], "exact_answer": "yes", "type": "yesno", "id": "60290c2b1cb411341a00010a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 852, "text": "Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. Here, we investigate the genetic population structure of this invasive fruit fly, with a focus on the eastern United States. We sequenced six X-linked gene fragments from 246 individuals collected from a total of 12 populations. We examine patterns of genetic diversity within and between populations and explore alternative colonization scenarios using approximate Bayesian computation. Our results indicate high levels of nucleotide diversity in this species and suggest that the recent invasions of Europe and the continental United States are independent demographic events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25158796", "endSection": "abstract" } ] }, { "body": "Which tools have been developed for identifying and visualising ncRNA promoters?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31680159", "http://www.ncbi.nlm.nih.gov/pubmed/33005306" ], "ideal_answer": [ "Epd, ncpro-ml and ucsc genome browser are tools that have been developed for identifying and visualising ncRNA promoters.", "The Eukaryotic Promoter Database (EPD) and ncPro-ML" ], "exact_answer": [ [ "Eukaryotic Promoter Database", "EPD" ], [ "ncPro-ML" ] ], "type": "list", "id": "602918381cb411341a00010c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "EPD in 2020: enhanced data visualization and extension to ncRNA promoters.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31680159", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1268, "text": "The Eukaryotic Promoter Database (EPD), available online at https://epd.epfl.ch, provides accurate transcription start site (TSS) information for promoters of 15 model organisms plus corresponding functional genomics data that can be viewed in a genome browser, queried or analyzed via web interfaces, or exported in standard formats (FASTA, BED, CSV) for subsequent analysis with other tools. Recent work has focused on the improvement of the EPD promoter viewers, which use the UCSC Genome Browser as visualization platform. Thousands of high-resolution tracks for CAGE, ChIP-seq and similar data have been generated and organized into public track hubs. Customized, reproducible promoter views, combining EPD-supplied tracks with native UCSC Genome Browser tracks, can be accessed from the organism summary pages or from individual promoter entries. Moreover, thanks to recent improvements and stabilization of ncRNA gene catalogs, we were able to release promoter collections for certain classes of ncRNAs from human and mouse. Furthermore, we developed automatic computational protocols to assign orphan TSS peaks to downstream genes based on paired-end (RAMPAGE) TSS mapping data, which enabled us to add nearly 9000 new entries to the human promoter collection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31680159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "ncPro-ML: An integrated computational tool for identifying non-coding RNA promoters in multiple species.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33005306", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 750, "text": "The promoter is located near the transcription start sites and regulates transcription initiation of the gene. Accurate identification of promoters is essential for understanding the mechanism of gene regulation. Since experimental methods are costly and ineffective, developing efficient and accurate computational tools to identify promoters are necessary. Although a series of methods have been proposed for identifying promoters, none of them is able to identify the promoters of non-coding RNA (ncRNA). In the present work, a new method called ncPro-ML was proposed to identify the promoter of ncRNA in Homo sapiens and Mus musculus, in which different kinds of sequence encoding schemes were used to convert DNA sequences into feature vectors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33005306", "endSection": "abstract" } ] }, { "body": "What is the mode of administration of AZD8601?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32438492" ], "ideal_answer": [ "AZD8601 is administered intradermally." ], "exact_answer": [ "Intradermal" ], "type": "factoid", "id": "602c19e71cb411341a00011a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF-A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32438492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF-A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32438492", "endSection": "abstract" } ] }, { "body": "What is SAR425899?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31808298" ], "ideal_answer": [ "SAR425899 ia a dual glucagon-like peptide-1 receptor/glucagon receptor agonist." ], "type": "summary", "id": "602c1fcc1cb411341a000120", "snippets": [ { "offsetInBeginSection": 6, "offsetInEndSection": 244, "text": "o evaluate the change in insulin sensitivity, \u03b2-cell function and glucose absorption after 28\u2009days of treatment with high and low doses of SAR425899, a novel dual glucagon-like peptide-1 receptor/glucagon receptor agonist, versus placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31808298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Dual glucagon-like peptide-1 receptor/glucagon receptor agonist SAR425899 improves beta-cell function in type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31808298", "endSection": "title" } ] }, { "body": "Which class of disorders are caused by AMPA receptor GluA2 subunit defects?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31300657" ], "ideal_answer": [ "Mutations in the AMPA receptor GluA2 subunit cause a variety of neurodevelopmental disorders including autism spectrum disorder.", "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Mutations lead to a decrease in agonist-evoked current mediated by mutant subunits.", "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes.", "AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. De-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.", "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders." ], "exact_answer": [ "Neurodevelopmental disorders" ], "type": "factoid", "id": "6030fe7a1cb411341a000128", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31300657", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1146, "text": "AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31300657", "endSection": "abstract" } ] }, { "body": "Is Hunter's disease is associated with the X Chromosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22246721", "http://www.ncbi.nlm.nih.gov/pubmed/31046699", "http://www.ncbi.nlm.nih.gov/pubmed/21062272", "http://www.ncbi.nlm.nih.gov/pubmed/25044788", "http://www.ncbi.nlm.nih.gov/pubmed/3100113", "http://www.ncbi.nlm.nih.gov/pubmed/9604546", "http://www.ncbi.nlm.nih.gov/pubmed/1294876", "http://www.ncbi.nlm.nih.gov/pubmed/9611068", "http://www.ncbi.nlm.nih.gov/pubmed/6418082", "http://www.ncbi.nlm.nih.gov/pubmed/9375851", "http://www.ncbi.nlm.nih.gov/pubmed/20052546", "http://www.ncbi.nlm.nih.gov/pubmed/23634718", "http://www.ncbi.nlm.nih.gov/pubmed/1481858", "http://www.ncbi.nlm.nih.gov/pubmed/17345554", "http://www.ncbi.nlm.nih.gov/pubmed/21834048", "http://www.ncbi.nlm.nih.gov/pubmed/2499679", "http://www.ncbi.nlm.nih.gov/pubmed/1908009", "http://www.ncbi.nlm.nih.gov/pubmed/8807335", "http://www.ncbi.nlm.nih.gov/pubmed/1642233", "http://www.ncbi.nlm.nih.gov/pubmed/1678247" ], "ideal_answer": [ "Yes, Hunter's disease is associated with the X Chromosome.", "Yes, the X Chromosome is associated with the X chromosome.", "Hunter's disease is associated with the X chromosome." ], "exact_answer": "yes", "type": "yesno", "id": "60327e541cb411341a00013e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Segregation analysis on five samples of families with Hunter's syndrome (158 cases overall) shows that the mutant allele segregates in agreement with Mendelian expectations for an X linked recessive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1908009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "The utility of polymerase chain reaction (PCR) amplification of amelogenin gene as a reliable and rapid means of determination of sex chromosomes was tested in 20 patients of X-linked disorders (Duchenne muscular dystrophy, haemophilia and Wiscott-Aldrich and Hunter's syndromes), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9604546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "We describe a 3 year old girl with the typical clinical features of the X linked recessive condition, Hunter's disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6418082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "We describe a 3 year old girl with the typical clinical features of the X linked recessive condition, Hunter's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6418082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Hunter's disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6418082", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Further evidence localising the gene for Hunter's syndrome to the distal region of the X chromosome long arm.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2499679", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Full expression of Hunter's disease in a female with an X-chromosome deletion leading to non-random inactivation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3100113", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Hunter disease in a girl caused by R468Q mutation in the iduronate-2-sulfatase gene and skewed inactivation of the X chromosome carrying the normal allele.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9375851", "endSection": "title" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1333, "text": "These findings strongly suggest that the severe form of Hunter disease in this girl was the result of selective expression of the maternal allele carrying the missense mutation R468Q, which in turn resulted from skewed X inactivation of the paternal nonmutant X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9375851", "endSection": "abstract" }, { "offsetInBeginSection": 1336, "offsetInEndSection": 1463, "text": "LUSIONS: This is a report of a female with a 10.6 Mb Xq27-28 deletion with skewed inactivation of the deleted X chromosome. Con", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23634718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Brother/sister siblings affected with Hunter disease: evidence for skewed X chromosome inactivation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9611068", "endSection": "title" }, { "offsetInBeginSection": 277, "offsetInEndSection": 406, "text": "The normal X chromosome was preferentially inactivated, supporting the view that the translocation had disrupted the Hunter gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2499679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1678247", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "INTRODUCTION: Hunter syndrome, or mucopolysaccharidosis type II, is an inherited disease linked to the X chromosome that is caused by a deficit of the enzyme iduronate-2-sulfatase and its main symptoms affect the bones, neurological system and the viscera.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17345554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "INTRODUCTION: Hunter syndrome, or mucopolysaccharidosis type II, is an inherited disease linked to the X chromosome that is caused by a deficit of the enzyme iduronate-2-sulfatase and its main symptoms affect the bones, neurological system and the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17345554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Mucopolysaccharidosis type II (MPS II, Hunter disease) is an X chromosome-linked inherited metabolic disease caused by mutations resulting in deficiency of activity of iduronate-2-sulfatase (IDS) and accumulation of undegraded glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate. Previous", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21834048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Mucopolysaccharidosis type II (MPS-II, Hunter disease) is a X-linked recessive disorder. Affe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20052546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme, iduronate-2-sulfatase (IDS). Pheno", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Hunter disease or mucopolysaccharidosis type II is an X-linked disease caused by the deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8807335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase (IDS). Two a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22246721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "We report the results of studies on the characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in a karyotypically normal girl with Hunter disease (mucopolysaccharidosis type II). So", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1642233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "BACKGROUND: Hunter syndrome (mucopolysaccharidosis type II) is a recessive X-linked disorder due to mutations in the iduronate 2-sulfatase (IDS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31046699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Familial X-chromosome inactivation (XCI) skewing was investigated in a family in which a female mucopolysaccharidosis type II (MPS II) (Hunter syndrome, an X-linked genetic disease) occurred. Among e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21062272", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1352, "text": "Studies using BrdU indicated that the deleted X chromosome was consistently late replicating, and as a result the Hunter gene was fully expressed on the other X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3100113", "endSection": "abstract" }, { "offsetInBeginSection": 1358, "offsetInEndSection": 1479, "text": "All mucopolysaccharidosis are autosomal recessive disorders, except for Hunter's syndrome that is X-linked and recessive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1294876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1481858", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 150, "text": "Hunter syndrome (mucopolysaccharidosis type II) is a recessive X-linked disorder due to mutations in the iduronate 2-sulfatase (IDS) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31046699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Hunter disease is an X-linked recessive mucopolysaccharide storage disorder caused by iduronate-2-sulfatase deficiency and is rare in females.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9375851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Hunter disease is an X-linked recessive disorder caused by a deficiency of iduronate-2-sulfatase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9611068", "endSection": "abstract" } ] }, { "body": "Where are integrins localized in a cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32584192", "http://www.ncbi.nlm.nih.gov/pubmed/32950537" ], "ideal_answer": [ "Integrins are transmembrane glycoproteins that are broadly distributed in living organisms." ], "exact_answer": [ "transmembrane" ], "type": "factoid", "id": "6032899c1cb411341a000144", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "The extracellular domain of plasma membrane integrin \u03b1v\u03b23", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32584192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Integrins are transmembrane glycoproteins that are broadly distributed in living organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32950537", "endSection": "abstract" }, { "offsetInBeginSection": 660, "offsetInEndSection": 750, "text": "The immunofluorescence results showed that Bmintegrin \u03b21 was located in the cell membrane ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32950537", "endSection": "abstract" } ] }, { "body": "What is a bacteriocin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31483516", "http://www.ncbi.nlm.nih.gov/pubmed/31794868", "http://www.ncbi.nlm.nih.gov/pubmed/31705720" ], "ideal_answer": [ "Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives.\nOne such strategy involves using narrow-spectrum protein antibiotics (so-called bacteriocins), which diverse bacteria use to compete against closely related species." ], "exact_answer": [ "antimicrobial peptide of bacteria" ], "type": "factoid", "id": "6032a0e21cb411341a000148", "snippets": [ { "offsetInBeginSection": 513, "offsetInEndSection": 679, "text": "One such strategy involves using narrow-spectrum protein antibiotics (so-called bacteriocins), which diverse bacteria use to compete against closely related species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31705720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Many enterococcal strains produce bacteriocins, which could be useful as natural food preservatives through inhibition of pathogenic and spoilage microorganisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31794868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31483516", "endSection": "abstract" } ] }, { "body": "What protein complex is altered in \"Coffin-Siris syndrome\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32161024", "http://www.ncbi.nlm.nih.gov/pubmed/31706665", "http://www.ncbi.nlm.nih.gov/pubmed/29907796", "http://www.ncbi.nlm.nih.gov/pubmed/30879640", "http://www.ncbi.nlm.nih.gov/pubmed/29698805", "http://www.ncbi.nlm.nih.gov/pubmed/30838730" ], "ideal_answer": [ "he genes causative of CSS mainly encode the SWI/SNF complex, which contributes to chromatin remodeling and regulates the access of transcriptional factors to specific gene sites.", "Report. Mutations in the BAF-Complex Subunit DPF2 Are Associated with Coffin-Siris Syndrome. Variants affecting the function of different subunits of the BAF chromatin-remodelling complex lead to various neurodevelopmental syndromes, including Coffin-Siris syndrome." ], "exact_answer": [ "SWI/SNF complex" ], "type": "factoid", "id": "6032a8b91cb411341a000149", "snippets": [ { "offsetInBeginSection": 421, "offsetInEndSection": 486, "text": "Mutations in other SWI/SNF components cause Coffin-Siris syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30879640", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 348, "text": " ARID2 encodes a member of the SWItch/sucrose non-fermentable chromatin remodeling complex. Other genes encoding subunits of this complex, such as ARID1A, ARID1B, and SMARCA2, are mutated in association with Coffin-Siris syndrome (CSS) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838730", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 362, "text": "MARCB1 encodes a subunit of the SWI/SNF complex involved in chromatin remodeling. Pathogenic variants (PV) in this gene can give rise to three conditions. Heterozygous loss-of-function germline PV cause rhabdoid tumor predisposition syndrome and schwannomatosis. Missense PV and small in-frame deletions in exons 8 and 9 result in Coffin-Siris syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29907796", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 315, "text": " subunit of the SWI/SNF complex, have been linked to intellectual disabilities in 3 case reports including one which describes frameshift mutations in ARID2 in 2 patients with features resembling Coffin-Siris syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29698805", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 358, "text": "The genes causative of CSS mainly encode the SWI/SNF complex, which contributes to chromatin remodeling and regulates the access of transcriptional factors to specific gene sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32161024", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 246, "text": "Coffin-Siris syndrome (CSS) is a neurodevelopmental disorder characterized by somatic dysmorphic features, developmental and speech delay. It is due to mutations in many different genes, belonging to BAF chromatin-remodelling complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31706665", "endSection": "abstract" } ] }, { "body": "What is Aortitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32234379", "http://www.ncbi.nlm.nih.gov/pubmed/19867969", "http://www.ncbi.nlm.nih.gov/pubmed/21787438", "http://www.ncbi.nlm.nih.gov/pubmed/27471062", "http://www.ncbi.nlm.nih.gov/pubmed/22991323", "http://www.ncbi.nlm.nih.gov/pubmed/23891316", "http://www.ncbi.nlm.nih.gov/pubmed/28511923", "http://www.ncbi.nlm.nih.gov/pubmed/33186247", "http://www.ncbi.nlm.nih.gov/pubmed/21253370", "http://www.ncbi.nlm.nih.gov/pubmed/12003723", "http://www.ncbi.nlm.nih.gov/pubmed/22624966", "http://www.ncbi.nlm.nih.gov/pubmed/33061068", "http://www.ncbi.nlm.nih.gov/pubmed/29701396", "http://www.ncbi.nlm.nih.gov/pubmed/31664480", "http://www.ncbi.nlm.nih.gov/pubmed/21415189", "http://www.ncbi.nlm.nih.gov/pubmed/19734736", "http://www.ncbi.nlm.nih.gov/pubmed/32390100" ], "ideal_answer": [ "Aortitis is the inflammation of the aorta due to various causes, such as the manifestation of an underlying infectious or noninfectious disease process.", "Aortitis is an inflammation of the aorta due to various causes. It can be a symptom of an underlying infectious or non-infectious disease process.", "Aortitis is inflammation of the aorta due to various causes. It can be caused by an underlying infectious or non-infectious disease process.", "Aortitis is the inflammation of the aorta due to various causes. Aortitis is classified as non-infectious or infectious.", "Aortitis includes conditions with infectious or non-infectious etiology, characterized by inflammatory changes in one or more layers in aortic wall." ], "exact_answer": [ "inflammation of the aorta" ], "type": "factoid", "id": "60314c361cb411341a00012e", "snippets": [ { "offsetInBeginSection": 19, "offsetInEndSection": 84, "text": "Aortitis is the inflammation of the aorta due to various causes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Aortitis can be the manifestation of an underlying infectious or noninfectious disease process. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31664480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Aortitis\u00a0includes conditions with infectious or non-infectious etiology, characterized by inflammatory changes in one or more layers in aortic wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32390100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Aortitis and periaortitis are inflammatory diseases of the aorta and its main branches; they differ in the extension of inflammation, which is confined to the aortic wall in aortitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32234379", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 293, "text": "Aortitis is classified as non-infectious or infectious. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32234379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "\"Aortitis\" is a pathologic term that refers to an abnormal inflammation of the aortic wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22624966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "IgG4 related thoracic aortitis is a recent addition to the differential diagnosis for inflammatory aortic disease - a condition which is often underappreciated until complications arise such as aneurysmal formation or aortic dissection. C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28511923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "BACKGROUND Inflammation of the aortic wall, known as aortitis, is a rare clinical entity which is frequently asymptomatic, or identified when the patient presents with an aortic aneurysm or dissection. It i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27471062", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 169, "text": "Syphilitic aortitis is a productive inflammatory process, the earliest and most constant feature of which is a perivascular round cell infiltration in the adventitia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19867969", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 449, "text": "Non-infectious aortitis represents a common feature of large-vessel vasculitides but can also be isolated or associated with other rheumatologic conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32234379", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 163, "text": "Aortitis is a subtype of the more general term \"vasculitis\", an inflammatory condition of infectious or noninfectious origin involving the vessel wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22991323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Aortitis and periaortitis are inflammatory diseases of the aorta and its main branches; they differ in the extension of inflammation, which is confined to the aortic wall in aortitis, and spreads to the periaortic space in periaortitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32234379", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 89, "text": "Takayasu aortitis is a well known yet rare form of large vessel vasculitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29701396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Aortitis is a general term denoting inflammation of the aortic wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21787438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "PURPOSE OF REVIEW: Aortitis is the inflammation of the aorta due", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Aortitis is the all-encompassing pathological term ascribed to inflammation of the aorta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21253370", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Aortitis is typically a chronic, progressive disease manifestation associated with large vessel vasculitidies, most notably giant cell, Takayasu arteritis, and a newly described entity, isolated aortitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19734736", "endSection": "abstract" }, { "offsetInBeginSection": 1489, "offsetInEndSection": 1657, "text": " TEACHING POINTS : \u2022 Aortitis is an inflammatory condition of infectious/nonin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22991323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Aortitis is a pathological term that refers to the inflammation of one or more layers of the aortic wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33061068", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Aortitis is a pathological term designating inflammation of the aortic wall, regardless of its cause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Aortitis is defined as an inflammatory process that involves one or more layers of the aortic wall (internal elastic lamina, tunica media, and adventitia) and can be caused by multiple mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12003723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Aortitis is a general term that refers to a broad category of infectious or noninfectious conditions in which there is abnormal inflammation of the aortic wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415189", "endSection": "abstract" } ] }, { "body": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28580156", "http://www.ncbi.nlm.nih.gov/pubmed/33014503", "http://www.ncbi.nlm.nih.gov/pubmed/29157612", "http://www.ncbi.nlm.nih.gov/pubmed/32775816", "http://www.ncbi.nlm.nih.gov/pubmed/31211492", "http://www.ncbi.nlm.nih.gov/pubmed/33269653", "http://www.ncbi.nlm.nih.gov/pubmed/29468524", "http://www.ncbi.nlm.nih.gov/pubmed/23801135", "http://www.ncbi.nlm.nih.gov/pubmed/27316721", "http://www.ncbi.nlm.nih.gov/pubmed/23801138", "http://www.ncbi.nlm.nih.gov/pubmed/26250536", "http://www.ncbi.nlm.nih.gov/pubmed/30244358", "http://www.ncbi.nlm.nih.gov/pubmed/25671135", "http://www.ncbi.nlm.nih.gov/pubmed/31579342", "http://www.ncbi.nlm.nih.gov/pubmed/26886414", "http://www.ncbi.nlm.nih.gov/pubmed/27516889", "http://www.ncbi.nlm.nih.gov/pubmed/31222819", "http://www.ncbi.nlm.nih.gov/pubmed/26805758", "http://www.ncbi.nlm.nih.gov/pubmed/31631463", "http://www.ncbi.nlm.nih.gov/pubmed/26781021", "http://www.ncbi.nlm.nih.gov/pubmed/30009125", "http://www.ncbi.nlm.nih.gov/pubmed/27725549", "http://www.ncbi.nlm.nih.gov/pubmed/32492687" ], "ideal_answer": [ "The syndromes that are part of Castleman's disease AKA TAFRO are:1) organomegaly, 2) anasarca, 3) myelofibrosis, 4) thrombocytopenia and 5) reticulin fibrosis.", "TAFRO (or Castleman-Kojima) syndrome has been gradually recognized in recent years. It is a systemic inflammatory disease characterized by thrombocytopenia (T), anasarca (A), myelofibrosis/fever (F), renal dysfunction/reticulin fibrosis (R), and organomegaly (O).", "TAFRO syndrome is defined as CD with thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly.", "The syndromes that are part of Castleman's disease AKA TAFRO are organomegaly, anasarca, myelofibrosis, thrombocytopenia, reticulin fibrosis and renal dysfunction.", "The syndromes that are part of Castleman's disease AKA TAFRO are organomegaly, anasarca, myelofibrosis, thrombocytopenia and reticulin fibrosis. There is also renal dysfunction.", "TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly).", "TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) is an atypical manifestation of multicentric Castleman's disease." ], "exact_answer": [ [ "thrombocytopenia" ], [ "anasarca" ], [ "myelofibrosis" ], [ "renal dysfunction", "reticulin fibrosis" ], [ "organomegaly" ] ], "type": "list", "id": "60314ce01cb411341a00012f", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 268, "text": ": Although thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly (TAFRO) syndrome was first described as a variant of idiopathic multicentric Castleman disease (CD), patients with TAFRO syndrome demonstrate more aggressive clinical features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31211492", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 410, "text": "Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a severe subtype of idiopathic multicentric Castleman's disease, characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, and organomegaly. Renal complication of this disease can be life-threatening and sometimes requires hemodialysis, but it has not been elucidated in detail.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32775816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) is an atypical manifestation of multicentric Castleman's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30244358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "Castleman-Kojima disease (TAFRO syndrome) : a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly : a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23801135", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "BACKGROUND: Castleman-Kojima disease (TAFRO Syndrome) is characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and histopathology pattern of atypical Castleman's disease (CD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25671135", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 358, "text": "A unique clinicopathologic variant of multicentric Castleman's disease, TAFRO (i.e., thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly) syndrome, was recently proposed in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26250536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31579342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Thrombocytopenia (T), anasarca (A), myelofibrosis (F), renal dysfunction (R), and organomegaly (O) (TAFRO) syndrome is a variant of multicentric Castleman's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27516889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Introduction: Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a severe subtype of idiopathic multicentric Castleman's disease, characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, and organomegaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32775816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Recently, a unique clinicopathologic variant of multicentric Castleman disease, TAFRO (i.e. thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis and organomegaly) syndrome, has been identified in Japan. Previo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33269653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "BACKGROUND: Although thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly (TAFRO) syndrome was first described as a variant of idiopathic multicentric Castleman disease (CD), patients with TAFRO syndrome demonstrate more aggressive clinical fea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31211492", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly (TAFRO) syndrome is a unique clinicopathologic subtype of multicentric Castleman's disease that has recently been identified in Japan. Howev", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29468524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is a unique clinicopathologic variant of multicentric Castleman's disease that has recently been identified in Japan. Previ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26781021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Thromboc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction and organomegaly (TAFRO) syndrome is a variant of Castleman's disease recently identified in Japan. A 73", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27725549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Thrombocytopenia, anasarca, fever, renal insufficiency, and organomegaly constitute TAFRO syndrome, a variant of Castleman disease. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30009125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is considered as a unique clinicopathologic variant of multicentric Castleman's disease and is recently reported in Japan. This ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26886414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "INTRODUCTION: Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized and rare clinical subtype of Castleman", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492687", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 418, "text": "The pathophysiology and comorbidities of TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly), which is thought to be a variant of multicentric Castleman's disease, are not fully understood, and there are few data on the effectiveness of treatments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33014503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is considered as a unique clinicopathologic variant of multicentric Castleman's disease and is recently reported in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26886414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly (TAFRO) syndrome is a unique clinicopathologic subtype of multicentric Castleman's disease that has recently been identified in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29468524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is a unique clinicopathologic variant of multicentric Castleman's disease that has recently been identified in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26781021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "INTRODUCTION: Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized and rare clinical subtype of Castleman disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492687", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 251, "text": "TAFRO represents the constellation of symptoms (Thrombocytopenia, Anasarca, MyeloFibrosis, Renal failure, Organomegaly).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28580156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157612", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 417, "text": "TAFRO syndrome is a newly identified disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31222819", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 250, "text": "Recently, a new variant of the disease was reported and named TAFRO syndrome, an acronym for thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27316721", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 625, "text": "Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26805758", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 334, "text": "reported a new disease concept, TAFRO syndrome, named from thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23801138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Castleman-Kojima disease, also known as idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO), is a recently recognized systemic inflammatory disorder with a characteristic series of clinical symptoms, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31631463", "endSection": "abstract" } ] }, { "body": "What is known about the protein Curli?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31932609", "http://www.ncbi.nlm.nih.gov/pubmed/31954994", "http://www.ncbi.nlm.nih.gov/pubmed/32043464" ], "ideal_answer": [ "A major component of bacterial biofilms is curli amyloid fibrils secreted by the curli biogenesis system.\nCurli is a bacterial \u03b1-synuclein (\u03b1Syn) which is deposited first in the enteric nervous system and amyloid deposits are propagated in a prion like manner to the central nervous system.\ncurli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid \u03b1-synuclein (\u03b1Syn), we reveal that colonization with curli-producing Escherichia coli promotes \u03b1Syn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate \u03b1Syn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate \u03b1Syn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities." ], "type": "summary", "id": "60327f331cb411341a00013f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A major component of bacterial biofilms is curli amyloid fibrils secreted by the curli biogenesis system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31932609", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 707, "text": "Curli is a bacterial \u03b1-synuclein (\u03b1Syn) which is deposited first in the enteric nervous system and amyloid deposits are propagated in a prion like manner to the central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31954994", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 1185, "text": "curli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid \u03b1-synuclein (\u03b1Syn), we reveal that colonization with curli-producing Escherichia coli promotes \u03b1Syn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate \u03b1Syn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate \u03b1Syn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32043464", "endSection": "abstract" } ] }, { "body": "List the core lung matrisome proteins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30774578", "http://www.ncbi.nlm.nih.gov/pubmed/29615673" ], "ideal_answer": [ "LGALS7, \nASPN, \nHSP90AA1, \nHSP90AB1,\nCOL1A1, \nSCGB1A1, \nTAGLN, \nPSEN2, \nTSPAN1, \nCTSB, \nAGR2, \nCSPG2,\nSERPINB3,\nfibronectin,\nemilin-1,\nversican,\ndecorin" ], "exact_answer": [ [ "HSP90AB1" ], [ "LGALS7" ], [ "ASPN" ], [ "HSP90AA1" ], [ "emilin-1" ], [ "fibronectin" ], [ "versican" ], [ "decorin" ], [ "SERPINB3" ], [ "CSPG2" ], [ "AGR2" ], [ "CTSB" ], [ "COL1A1" ], [ "SCGB1A1" ], [ "TAGLN" ], [ "PSEN2" ], [ "TSPAN1" ] ], "type": "list", "id": "60322b501cb411341a000137", "snippets": [ { "offsetInBeginSection": 1694, "offsetInEndSection": 1730, "text": "LGALS7, ASPN, HSP90AA1 and HSP90AB1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30774578", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1592, "text": " COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30774578", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 897, "text": " The remodeling of the scaffold was characterized by an initial phase with cell proliferation and high production of cell adhesion proteins such as emilin-1 and fibronectin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29615673", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1135, "text": "f proteoglycans, such as versican and decorin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29615673", "endSection": "abstract" } ] }, { "body": "Can Freund's complete adjuvant induce arthritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31857078", "http://www.ncbi.nlm.nih.gov/pubmed/31721330", "http://www.ncbi.nlm.nih.gov/pubmed/32048253", "http://www.ncbi.nlm.nih.gov/pubmed/32043729" ], "ideal_answer": [ "Yes, Rheumatoid arthritis (RA) was induced by Freund's Complete Adjuvant (FCA; 1 mg/0.1 ml paraffin oil), injected subcutaneously on days 0, 30 and 40" ], "exact_answer": "yes", "type": "yesno", "id": "60328f351cb411341a000145", "snippets": [ { "offsetInBeginSection": 243, "offsetInEndSection": 286, "text": "complete Freund's adjuvant (CFA) induced RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31721330", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 266, "text": "The RA model was established using Freund's complete adjuvant, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31857078", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 546, "text": " Rheumatoid arthritis (RA) was induced by Freund's Complete Adjuvant (FCA; 1\u00a0mg/0.1\u00a0ml paraffin oil), injected subcutaneously on days 0, 30 and 40", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32048253", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 586, "text": "The rats were made arthritic using a subcutaneous injection with 0.1\u2009ml complete Freund's adjuvant (CFA) into the footpad of the left hind paw.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32043729", "endSection": "abstract" } ] }, { "body": "Can saponins be used as adjuvant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32012760", "http://www.ncbi.nlm.nih.gov/pubmed/32062145", "http://www.ncbi.nlm.nih.gov/pubmed/32098409", "http://www.ncbi.nlm.nih.gov/pubmed/31833496", "http://www.ncbi.nlm.nih.gov/pubmed/32101001" ], "ideal_answer": [ "Yes,\nsaponin is an ideal adjuvant candidate." ], "exact_answer": "yes", "type": "yesno", "id": "603291f21cb411341a000146", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "We report the design, synthesis, immunological evaluation, and conformational analysis of new saponin variants as promising vaccine adjuvants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31833496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The purified active fraction of Albizia julibrissin saponin (AJSAF) is an ideal adjuvant candidate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32012760", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 685, "text": "BALB/c mice immunized with subcutaneous injections of the recombinant protein with or without liposome/saponin (Lip/Sap) as an adjuvant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32062145", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 382, "text": " a saponin-based Matrix-M\u2122 adjuvant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32098409", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1160, "text": ". These results confirm that Momordica saponins are a viable natural source to provide potent saponin adjuvants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32101001", "endSection": "abstract" } ] }, { "body": "Is erabutoxin b usually found in plants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6279398", "http://www.ncbi.nlm.nih.gov/pubmed/7526378", "http://www.ncbi.nlm.nih.gov/pubmed/5964959", "http://www.ncbi.nlm.nih.gov/pubmed/4076189", "http://www.ncbi.nlm.nih.gov/pubmed/1067597", "http://www.ncbi.nlm.nih.gov/pubmed/21422738", "http://www.ncbi.nlm.nih.gov/pubmed/8027999", "http://www.ncbi.nlm.nih.gov/pubmed/17710455", "http://www.ncbi.nlm.nih.gov/pubmed/4664580", "http://www.ncbi.nlm.nih.gov/pubmed/7407041", "http://www.ncbi.nlm.nih.gov/pubmed/2514275" ], "ideal_answer": [ "Erabutoxin b is a short-chain neurotoxic peptide purified from the venom of the sea snake Laticauda semifasciata.", "No, erabutoxin b is not found in plants, it is a transmembrane toxin" ], "exact_answer": "no", "type": "yesno", "id": "603bc16b1cb411341a000158", "snippets": [ { "offsetInBeginSection": 151, "offsetInEndSection": 269, "text": "The variants are the curaremimetic toxin alpha from Naja nigricollis and erabutoxin a or b from Laticauda semifasciata", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7526378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The three-dimensional structure of erabutoxin b, a short-chain neurotoxic peptide purified from the venom of the sea snake Laticauda semifasciata, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8027999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "THe characteristic feature of the crystal structure of erabutoxin b, a short neurotoxin from Laticauda semifasciata, and alpha-cobratoxin, a long neurotoxin from Naja naja siamensis, is the presence of a triple-stranded antiparallel pleated beta-sheet structure formed by the central and the third peptide loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6279398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 370, "text": "Here we examine the actions of six snake neurotoxins (alpha-cobratoxin from Naja naja siamensis, erabutoxin-a and b from Laticauda semifasciata; CM12 from N. haje annulifera, toxin III 4 from Notechis scutatus and a long toxin from N. haje) on nicotinic acetylcholine receptors in the cercal afferent, giant interneuron 2 synapse of the cockroach, Periplaneta americana.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17710455", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 513, "text": "The method was applied to a study of erabutoxin b molecule, a neurotoxic protein from a sea snake, to analyze the microenvironments of its single tryptophan and tyrosine residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7407041", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 810, "text": "The area of greatest similarity centered on residue position 25 of erabutoxin b, a locale that is conserved throughout the snake alpha-neurotoxins and their homologues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2514275", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 641, "text": "A systematic computer search of the three-dimensional structure of erabutoxin b (an alpha-neurotoxin from the false sea snake Laticauda semifasciata) was performed to identify the locality that most closely matched the amino acid compositions of the smaller alpha-conotoxins (from the marine snails Conus magus and Conus geographus).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2514275", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 346, "text": "Erabutoxin b is one of a family of snake venom neurotoxins, all low-molecular-weight proteins, which block neuromuscular transmission at the postsynaptic membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1067597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Erabutoxins a and b are neurotoxins isolated from venom of a sea snake Laticauda semifasciata (erabu-umihebi).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21422738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "The three-dimensional structure of erabutoxin b, a neurotoxin in the venom of the sea snake Laticauda semifasciata, has been determined from a 2.75 A resolution electron density map.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1067597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Erabutoxin c, a minor neurotoxic component of the venom of a sea snake Laticauda semifasciata, was isolated in pure form by repeated column chromatography on CM-cellulose columns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4664580", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 395, "text": "The study has established complete structural identity of the two sea-snake venom toxins, erabutoxin b and neurotoxin b, isolated from Laticauda semifasciata snakes taken in different Pacific Ocean waters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4076189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Studies on sea-snake venoms. Crystallization of erabutoxins a and b from Laticauda semifasciata venom.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/5964959", "endSection": "title" } ] }, { "body": "Are Toll-like receptors (TLRs) induced by microbes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31799626", "http://www.ncbi.nlm.nih.gov/pubmed/31462144", "http://www.ncbi.nlm.nih.gov/pubmed/31712269", "http://www.ncbi.nlm.nih.gov/pubmed/31865463", "http://www.ncbi.nlm.nih.gov/pubmed/33075123" ], "ideal_answer": [ "Yes,\nGram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-\u03b1 and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1\u03b2 into its mature form." ], "exact_answer": "yes", "type": "yesno", "id": "603285861cb411341a000141", "snippets": [ { "offsetInBeginSection": 291, "offsetInEndSection": 439, "text": "The C-type lectin receptor CLEC4E and Toll-like receptor TLR4 expressed by host cells are among the first line of defense in encountering pathogens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31462144", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 1042, "text": "Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-\u03b1 and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1\u03b2 into its mature form. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31865463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "During viral infection, viral nucleic acids are detected by virus sensor proteins including toll-like receptor 3 or retinoic acid-inducible gene I-like receptors (RLRs) in mammalian cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31799626", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 779, "text": "Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31712269", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 782, "text": "We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33075123", "endSection": "abstract" } ] }, { "body": "What is a decoy exosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27843457", "http://www.ncbi.nlm.nih.gov/pubmed/30651550", "http://www.ncbi.nlm.nih.gov/pubmed/21364924", "http://www.ncbi.nlm.nih.gov/pubmed/22396543" ], "ideal_answer": [ "exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity." ], "exact_answer": [ "an exosome may carry antigens as a decoy", "" ], "type": "factoid", "id": "60320ef51cb411341a000130", "snippets": [ { "offsetInBeginSection": 1028, "offsetInEndSection": 1177, "text": "exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30651550", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 971, "text": "Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21364924", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1357, "text": "Acting as a decoy, the HSP-bearing exosomes efficiently stimulated NK cell cytotoxicity and granzyme B production, up-regulated the expression of inhibitory receptor CD94, and down-regulated the expression of activating receptors CD69, NKG2D, and NKp44. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22396543", "endSection": "abstract" } ] }, { "body": "Can you summarize Myasthenia Gravis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32859770", "http://www.ncbi.nlm.nih.gov/pubmed/16155434", "http://www.ncbi.nlm.nih.gov/pubmed/11886578", "http://www.ncbi.nlm.nih.gov/pubmed/31998320", "http://www.ncbi.nlm.nih.gov/pubmed/24141560", "http://www.ncbi.nlm.nih.gov/pubmed/20067169", "http://www.ncbi.nlm.nih.gov/pubmed/19209651", "http://www.ncbi.nlm.nih.gov/pubmed/28654435", "http://www.ncbi.nlm.nih.gov/pubmed/28941526", "http://www.ncbi.nlm.nih.gov/pubmed/31937334", "http://www.ncbi.nlm.nih.gov/pubmed/21087811", "http://www.ncbi.nlm.nih.gov/pubmed/22428294", "http://www.ncbi.nlm.nih.gov/pubmed/16037773", "http://www.ncbi.nlm.nih.gov/pubmed/27690672", "http://www.ncbi.nlm.nih.gov/pubmed/33223079" ], "ideal_answer": [ "Myasthenia gravis (MG) is a neuromuscular disease which affects the central nervous system, dorsal root ganglia of the spinal cord, heart and in certain cases the pancreas. Two thirds of MG cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them.", "Myasthenia gravis (MG) is a neuromuscular disease resulting from a disorder of the central nervous system. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. MG can be symptomatic of focal cortical malformation, in which there is intraepithelial (usually intraepidermal) infiltration by neoplastic cells showing glandular differentiation. Clinical symptoms occur first after an age of approximately 30\u00a0years. Main manifestations include cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral", "Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles. The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction, the nicotinic acetylcholine receptor.", "Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles. The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction, the nicotinic acetylcholine receptor. Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.", "Myasthenia gravis (MG) is a neuromuscular disease resulting from a disorder of the extrapyramidal system. Pathogenesis is still unknown and temporal lobe has been thought to take part in the pathogenesis. MG can be symptomatic of focal cortical malformation, and few cases were reported. Clinical symptoms occur first after an age of approximately 30\u00a0years. Main manifestations include central nervous system (CNS) and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeoch" ], "type": "summary", "id": "603bc1a81cb411341a000159", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles. The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction, the nicotinic acetylcholine receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32859770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are the most common disorders of neuromuscular transmission in clinical practice. Disorders of the neuromuscular junction (NMJ) are characterized by fluctuating and fatigable weakness and include autoimmune, toxic, and genetic conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33223079", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 75, "text": "Myasthenia gravis is a rare autoimmune neuromuscular disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31937334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Myasthenia gravis is an autoimmune disease in which immunoglobulin G (IgG) autoantibodies are formed against the nicotinic acetylcholine receptor (AChR) or other components of the neuromuscular junction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31998320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Myasthenia gravis is a chronic neuromuscular disease characterized by muscular weakness and fatigability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16037773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Myasthenia Gravis is an organ-specific autoimmune disorder generaly thought to be caused by an antibody-mediated attack against the skeletal muscle nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22428294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "INTRODUCTION: myasthenia gravis is a neuromuscular junction disorder that can jeopardize the patient's life and has a high clinical polymorphism that makes it difficult to diagnose.PATIENTS AND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21087811", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 310, "text": "Myasthenia that affects children can be classified into the following 3 forms: transient neonatal myasthenia, congenital myasthenic syndromes, and juvenile myasthenia gravis (JMG).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28941526", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 101, "text": "Juvenile myasthenia gravis is a relatively rare autoimmune neuromuscular disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24141560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Myasthenia gravis is a common autoimmune disorder characterized by the presence of pathogenic antibodies directed against the acetylcholine receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11886578", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Myasthenia gravis is an autoimmune neuromuscular disorder characterized by skeletal muscle involvement, causing muscle weakness and fatigue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20067169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "INTRODUCTION: Myasthenia gravis is the most frequent acquired disorder of neuromuscular", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27690672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "PURPOSE OF REVIEW: Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28654435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Myasthenia gravis is a rare, auto-immune neuromuscular junction disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19209651", "endSection": "abstract" } ] }, { "body": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22470656", "http://www.ncbi.nlm.nih.gov/pubmed/25017277", "http://www.ncbi.nlm.nih.gov/pubmed/10465109", "http://www.ncbi.nlm.nih.gov/pubmed/1853883", "http://www.ncbi.nlm.nih.gov/pubmed/15772095", "http://www.ncbi.nlm.nih.gov/pubmed/12107442", "http://www.ncbi.nlm.nih.gov/pubmed/29866251", "http://www.ncbi.nlm.nih.gov/pubmed/16418967", "http://www.ncbi.nlm.nih.gov/pubmed/10802661", "http://www.ncbi.nlm.nih.gov/pubmed/25635170", "http://www.ncbi.nlm.nih.gov/pubmed/6495304", "http://www.ncbi.nlm.nih.gov/pubmed/9467007", "http://www.ncbi.nlm.nih.gov/pubmed/12026212", "http://www.ncbi.nlm.nih.gov/pubmed/8985498", "http://www.ncbi.nlm.nih.gov/pubmed/22090721", "http://www.ncbi.nlm.nih.gov/pubmed/3314666" ], "ideal_answer": [ "McKusick-Kaufman syndrome (MKKS) is a rare, recessively inherited syndrome reported mainly in young children. It is characterised by vaginal atresia with hydrometrocolpos, postaxial polydactyly, and congenital heart defect.", "Clinical symptoms of Kaufman-McKusick syndrome (KM) include postaxial polydactyly, hydrometrocolpos, and congenital heart disease.", "Mekusick-Kusick syndrome is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease.", "McKusick-Kaufman Syndrome (MKKS) is a rare, recessively inherited syndrome reported mainly in young children. It is characterised by vaginal atresia with hydrometrocolpos, postaxial polydactyly, and congenital heart defect.", "MKKS) is one of rare syndromes which presents as polydactyly, hydrometrocolpos (HMC) and cardiac anomalies.", "McKusick-Kaufman syndrome (MKKS) is a rare, recessively inherited syndrome reported mainly in young children and is characterised by vaginal atresia with hydrometrocolpos, postaxial polydactyly, and congenital heart defect.", "The Kaufman-McKusick syndrome (MK 23670) AKA McKusik-Kaufman syndrome, is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease" ], "exact_answer": [ [ "hydrometrocolpos" ], [ "polydactyly" ], [ "congenital heart disease" ] ], "type": "list", "id": "601ead101cb411341a000055", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "McKusick-Kaufman Syndrome (MKKS) is one of rare syndromes which presents as polydactyly, hydrometrocolpos (HMC) and cardiac anomalies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29866251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "McKusick-Kaufman syndrome (MKKS) is a rare, recessively inherited syndrome reported mainly in young children and is characterised by vaginal atresia with hydrometrocolpos, postaxial polydactyly, and congenital heart defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10465109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The Kaufman-McKusick syndrome (MK 23670) is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3314666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The Kaufman-McKusick syndrome (MK 23670) is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease. Mu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3314666", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 345, "text": "Although most cases of mucometrocolpos are sporadic, it may be part of an autosomal recessive condition, known as McKusick-Kaufman syndrome (MKS), including postaxial polydactyly and congenital heart disease as main findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985498", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 504, "text": "A triad of congenital HMC, polydactyly, and cardiac anomalies are the cardinal features of McKusick-Kaufman syndrome, which is also known as hydrometrocolpos-polydactyly syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635170", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "McKusick-Kaufman syndrome (MKS) is an autosomal recessive disorder characterized by post-axial polydactyly, congenital heart defects and hydrometrocolpos, a congenital structural abnormality of female genitalia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15772095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "McKusick-Kaufman syndrome (MKS, OMIM #236700) is a rare syndrome inherited in an autosomal recessive pattern with a phenotypic triad comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP), and congenital cardiac disease (CHD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "McKusick-Kaufman syndrome (MKKS, MIM 236700) is a human developmental anomaly syndrome comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP) and congenital heart disease (CHD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10802661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "OBJECTIVE: McKusick-Kaufman syndrome (MKS) is a rare autosomal recessive syndrome characterized by hydrometrocolpos (HMC) and postaxial polydactyly (PAP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25017277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "McKusick-Kaufman syndrome comprises hydrometrocolpos, polydactyly, and congenital heart defects and overlaps with Bardet-Biedl syndrome, comprising retinitis pigmentosa, polydactyly, obesity, mental retardation, and renal and genital anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12107442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "McKusick-Kaufman syndrome is a rare, autosomal, recessive disorder characterized by hydrometrocolpos, post-axial polydactyly, and congenital heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16418967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9467007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The McKusick-Dungy-Kaufman syndrome is characterized by hydrometrocolpos, polydactyly and congenital heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6495304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "McKusick-Kaufman syndrome (MKS) is a rare autosomal recessive condition consisting of congenital hydrometrocolpos, polydactyly and congenital heart defect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12026212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "McKusick-Kaufman syndrome is a rare autosomal recessive disease diagnosed by polydactyly, hydrometrocolpos, and congenital heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22470656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "McKusick-Kaufman syndrome is an autosomal recessive multiple malformation syndrome characterized by hydrometrocolpos and polydactyly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1853883", "endSection": "abstract" } ] }, { "body": "Is Ixodes a species of tick?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21153754", "http://www.ncbi.nlm.nih.gov/pubmed/26336217", "http://www.ncbi.nlm.nih.gov/pubmed/11296828", "http://www.ncbi.nlm.nih.gov/pubmed/25236960", "http://www.ncbi.nlm.nih.gov/pubmed/12938010", "http://www.ncbi.nlm.nih.gov/pubmed/31943036", "http://www.ncbi.nlm.nih.gov/pubmed/14500917", "http://www.ncbi.nlm.nih.gov/pubmed/27473852", "http://www.ncbi.nlm.nih.gov/pubmed/25035799", "http://www.ncbi.nlm.nih.gov/pubmed/21028959", "http://www.ncbi.nlm.nih.gov/pubmed/20101443", "http://www.ncbi.nlm.nih.gov/pubmed/30914054", "http://www.ncbi.nlm.nih.gov/pubmed/32327327", "http://www.ncbi.nlm.nih.gov/pubmed/23077588", "http://www.ncbi.nlm.nih.gov/pubmed/31887120", "http://www.ncbi.nlm.nih.gov/pubmed/32723642", "http://www.ncbi.nlm.nih.gov/pubmed/29448923", "http://www.ncbi.nlm.nih.gov/pubmed/28173840", "http://www.ncbi.nlm.nih.gov/pubmed/33010631", "http://www.ncbi.nlm.nih.gov/pubmed/14570115", "http://www.ncbi.nlm.nih.gov/pubmed/17089744", "http://www.ncbi.nlm.nih.gov/pubmed/23444797", "http://www.ncbi.nlm.nih.gov/pubmed/25333277", "http://www.ncbi.nlm.nih.gov/pubmed/12422585", "http://www.ncbi.nlm.nih.gov/pubmed/26586535", "http://www.ncbi.nlm.nih.gov/pubmed/30207871", "http://www.ncbi.nlm.nih.gov/pubmed/19184580", "http://www.ncbi.nlm.nih.gov/pubmed/25434042", "http://www.ncbi.nlm.nih.gov/pubmed/31720842", "http://www.ncbi.nlm.nih.gov/pubmed/16350531", "http://www.ncbi.nlm.nih.gov/pubmed/30079309", "http://www.ncbi.nlm.nih.gov/pubmed/27263092", "http://www.ncbi.nlm.nih.gov/pubmed/33059172", "http://www.ncbi.nlm.nih.gov/pubmed/31031164", "http://www.ncbi.nlm.nih.gov/pubmed/23975565", "http://www.ncbi.nlm.nih.gov/pubmed/19998007", "http://www.ncbi.nlm.nih.gov/pubmed/12880241", "http://www.ncbi.nlm.nih.gov/pubmed/27286701", "http://www.ncbi.nlm.nih.gov/pubmed/33002807" ], "ideal_answer": [ "Ixodes is a family of hard ticks.", "tick, Ixodes ricinus", "Yes, Ixodes is a species of tick.", "ixodid ticks hard ticks (family Ixodidae)" ], "exact_answer": "yes", "type": "yesno", "id": "603e43d51cb411341a00015e", "snippets": [ { "offsetInBeginSection": 26, "offsetInEndSection": 38, "text": "ixodid ticks", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33059172", "endSection": "title" }, { "offsetInBeginSection": 64, "offsetInEndSection": 77, "text": "ixodid ticks ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33059172", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 476, "text": " ixodid ticks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33059172", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 215, "text": "tick, Ixodes ricinus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33010631", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 331, "text": "hard ticks (family Ixodidae)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33002807", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 959, "text": "The two enzootic tick vectors, Ixodes affinis and Ixodes minor, rarely bite humans but are more important than the human biting \"bridge\" vector, Ixodes scapularis, in maintaining the enzootic spirochete cycle in nature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500917", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1252, "text": "is more common in coastal habitats, where a greater diversity of Ixodes species ticks are found feeding on small mammal hosts (four species when compared with only I. pacificus in other sampled habitats).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31943036", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 864, "text": "We found three of five previously reported tick species as well as a tick resembling the eastern North American tick Ixodes minor Neumann (which we here designate Ixodes \"Mojave morphotype\") on isolated Amargosa voles and Owens Valley voles (Microtus californicus vallicola Bailey) in Inyo County in 2012 and 2014.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26336217", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 590, "text": "THODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonotic diseases to humans. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29448923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Ectoparasites of Microtus californicus and Possible Emergence of an Exotic Ixodes Species Tick in California.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26336217", "endSection": "title" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1886, "text": "Since 2007, non-native tick species have been documented in the state every year, including Amblyomma americanum, Dermacentor andersoni, Dermacentor occidentalis, Dermacentor variabilis, Ixodes pacificus, Ixodes ricinus, Ixodes scapularis, Ixodes texanus, and Rhipicephalus sanguineus sensu lato (s.l.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32723642", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 631, "text": "in 1.5% of Ixodes species ticks and 3.6% of small mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31943036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Data-driven predictions and novel hypotheses about zoonotic tick vectors from the genus Ixodes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29448923", "endSection": "title" }, { "offsetInBeginSection": 152, "offsetInEndSection": 204, "text": "spirochetes and transmitted by Ixodes species ticks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500917", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 678, "text": "In this study, cutaneous bite-site lesions were analyzed using Affymetrix mouse genome 430A 2.0 arrays and histopathology at 1, 3, 6, and 12 hours after uninfected Ixodes scapularis nymphal tick attachment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23077588", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 357, "text": "The minimally vegetated, extremely arid desert surrounding the pools is essentially uninhabitable for Ixodes species ticks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25035799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Biology of Ixodes species ticks in relation to tick-borne zoonoses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12422585", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25333277", "endSection": "abstract" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 1468, "text": "Rickettsia conorii was found in virtually all non- Ixodes tick species from Albania and Turkey.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12938010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Ixodes anatis is a species of endophilic (nidicolous) tick species parasitizing brown kiwi (Apteryx mantelli). Even", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31031164", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Ixodes ariadnae is a tick species of bats so far reported only in Central Europe, with its description based on the female and nymph. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27473852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "BACKGROUND: Ixodes collaris Hornok, 2016 is a recently discovered tick species associated with bats", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30914054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Ixodes holocyclus (Acarina: Ixodidae) and Ixodes cornuatus (Acarina: Ixodidae) are two tick species found in the more densely populated areas of Australia and are known to be the cause of the neurotoxic disease tick paralysis in humans and mammals. Borre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25434042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Ixodes affinis Neumann (Acari: Ixodidae) is a hard-bodied tick species distributed throughout much of the southeastern United States. Alt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586535", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 492, "text": "ixodid tick fauna consists of 241 species in the genus Ixodes and 442 species in the genera Amblyomma, Anomalohimalaya, Bothriocroton, Cosmiomma, Dermacentor, Haemaphysalis, Hyalomma, Margaropus, Nosomma, Rhipicentor and Rhipicephalus in the family Ixodidae, with the genus Boophilus becoming a subgenus of the genus Rhipicephalus. The family Nutt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14570115", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 520, "text": "e following 16 ixodid tick species were identified: Ixodes fuscipes, Amblyomma auricularium, Amblyomma coelebs, Amblyomma dubitatum, Amblyomma geayi, Amblyomma humerale, Amblyomma latepunctatum, Amblyomma longirostre, Amblyomma naponense, Amblyomma nodosum, Amblyomma oblongoguttatum, Amblyomma ovale, Amblyomma romitii, Amblyomma rotundatum, Amblyomma scalpturatum, and Amblyomma varium. From these, A. aur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23975565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "In 2014, a new tick species, Ixodes inopinatus, was described, which is closely related to Ixodes ricinus. So fa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31720842", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 451, "text": "ontinent. Zoonotic Babesia is vectored by Ixodes ticks and is commonly transmitted in North America by Ixodes scapularis, the tick species responsible for transmitting the pathogens that also cause Lyme disease, Powassan virus, and anaplasmosis in hu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31887120", "endSection": "abstract" }, { "offsetInBeginSection": 2000, "offsetInEndSection": 2321, "text": "In addition to identifying novel, testable hypotheses about intrinsic features driving vectorial capacity across Ixodes tick species, our model identifies particular Ixodes species with the highest probability of carrying zoonotic diseases, offering specific targets for increased zoonotic investigation and surveillance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29448923", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 567, "text": "To date, the tick fauna of this area consists of 117 species in the following families: Argasidae-Argas (7 species), Carios (4 species) and Ornithodoros (2 species); Ixodidae-Amblyomma (8 species), Anomalohimalaya (2 species), Dermacentor (12 species), Haemaphysalis (44 species), Hyalomma (6 species), Ixodes (24 species) and Rhipicephalus (8 species).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20101443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "During a 3-yr comprehensive study, 196 ixodid ticks (9 species) were collected from 89 passerine birds (32 species) from 25 localities across Canada to determine the distribution of avian-associated tick species and endogenous Lyme disease spirochetes, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt, and Brenner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17089744", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 732, "text": "In the Polish fauna there are 19 species of ticks (Ixodida) recognized as existing permanently in our country: Argas reflexus, Argas polonicus, Carios vespertilionis, Ixodes trianguliceps, Ixodes arboricola, Ixodes crenulatus, Ixodes hexagonus, Ixodes lividus, Ixodes rugicollis, Ixodes caledonicus, Ixodes frontalis, Ixodes simplex, Ixodes vespertilionis, Ixodes apronophorus, Ixodes persulcatus, Ixodes ricinus, Haemaphysalis punctata, Haemaphysalis concinna, Dermacentor reticulatus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444797", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 1162, "text": "Occasionally, alien species of ticks transferred to the territory of Poland are recorded: Amblyomma sphenodonti, Amblyomma exornatum, Amblyomma flavomaculatum, Amblyomma latum, Amblyomma nuttalli, Amblyomma quadricavum, Amblyomma transversale, Amblyomma varanensis, Amblyomma spp., Dermacentor marginatus, Hyalomma aegyptium, Hyalomma marginatum, Ixodes eldaricus, Ixodes festai, Rhipicephalus rossicus, Rhipicephalus sanguineus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444797", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1104, "text": "Haemaphysalis leporispalustris (Packard) (one nymph, 14 larvae); the bird tick Ixodes brunneus Koch (two larvae); the American dog tick, Dermacentor variabilis (Say) (one nymph); and Ixodes affinis Neumann (one larva).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11296828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27263092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Diapause in ticks of the medically important Ixodes ricinus species complex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27263092", "endSection": "title" }, { "offsetInBeginSection": 527, "offsetInEndSection": 621, "text": "Herein, we report these ticks to represent three different species: Ixodes catarinensis n. sp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32327327", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 533, "text": "We found that 430 endemic ticks were from 3 Ixodes species: Ixodes pacificus, Ixodes spinipalpis, and Ixodes angustus, whereas Ixodes scapularis (n\u2009=\u2009111) was the most common species among the 119 nonendemic ticks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30207871", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 318, "text": "In total, 549 human-biting Ixodes ticks were submitted comprising both endemic and nonendemic species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30207871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Human-Biting Ixodes Ticks and Pathogen Prevalence from California, Oregon, and Washington.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30207871", "endSection": "title" }, { "offsetInBeginSection": 1531, "offsetInEndSection": 1668, "text": "In this study, we show that many nonendemic Ixodes ticks (119/549) are most likely acquired from travel to a different geographic region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30207871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The Ixodes ricinus species complex is a group of ticks distributed in almost all geographic regions of the world.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12880241", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1706, "text": "We report a tick associated with the enhancement of mammalian meat anaphylaxis after tick bite which is novel for both Australia and the world and establishes Ixodes (Endopalpiger) australiensis as a second tick species associated with mammalian meat allergy in Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Among the various species of hard ticks, Ixodes ricinus is the most frequently found tick throughout Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19998007", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 567, "text": " in humans. We aimed to identify intrinsic traits that predict which Ixodes tick species are confirmed or strongly suspected to be vectors of zoonotic pathogens.METHODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonoti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29448923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "A list of the 70 species of Australian ticks; diagnostic guides to and species accounts of Ixodes holocyclus (paralysis tick), Ixodes cornuatus (southern paralysis tick) and Rhipicephalus australis (Australian cattle tick); and consideration of the place of Australia in the evolution of ticks with comments on four controversial ideas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25236960", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Differentiation of medically important Euro-Asian tick species Ixodes ricinus, Ixodes persulcatus, Ixodes hexagonus, and Dermacentor reticulatus by polymerase chain reaction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21028959", "endSection": "title" }, { "offsetInBeginSection": 432, "offsetInEndSection": 734, "text": "All these I. granulatus ticks collected from Taiwan and Japan were genetically affiliated to a monophyletic group with highly homogeneous sequences (95.8-99.5% similarity), and can be discriminated from other species and subgenera of Ixodes ticks with a sequence divergence ranging from 13.6% to 62.9%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21153754", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 354, "text": "The phylogenetic relationships were analyzed by comparing the sequences of mitochondrial 16S ribosomal DNA gene obtained from 19 strains of ticks representing seven species of Ixodes and two outgroup species (Rhipicephalus sanguineus and Haemaphysalis inermis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19184580", "endSection": "abstract" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1542, "text": "e, I. woyliei n. sp. was only found on two I. o. fusciventer.CONCLUSIONS: Morphological and molecular data have confirmed the first new Australian Ixodes tick species described in ov", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28173840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "More than 800 tick species have been reported world-wide however only about 30 tick species feed on humans, among them Ixodes ricinus, which is the most frequent tick species biting humans in Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16350531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Description of a new tick species, Ixodes collaris n. sp. (Acari: Ixodidae), from bats (Chiroptera: Hipposideridae, Rhinolophidae) in Vietnam.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27286701", "endSection": "title" } ] }, { "body": "What is the active ingredient in the most common hand sanitizer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32459621", "http://www.ncbi.nlm.nih.gov/pubmed/30676276", "http://www.ncbi.nlm.nih.gov/pubmed/28279942", "http://www.ncbi.nlm.nih.gov/pubmed/29987197", "http://www.ncbi.nlm.nih.gov/pubmed/29502883", "http://www.ncbi.nlm.nih.gov/pubmed/26282413", "http://www.ncbi.nlm.nih.gov/pubmed/25726133", "http://www.ncbi.nlm.nih.gov/pubmed/32790662", "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "http://www.ncbi.nlm.nih.gov/pubmed/30969148", "http://www.ncbi.nlm.nih.gov/pubmed/21730079", "http://www.ncbi.nlm.nih.gov/pubmed/21219741", "http://www.ncbi.nlm.nih.gov/pubmed/33134040", "http://www.ncbi.nlm.nih.gov/pubmed/29322859", "http://www.ncbi.nlm.nih.gov/pubmed/32461409" ], "ideal_answer": [ "Evaluation of a benzalkonium chloride hand sanitizer in reducing transient Staphylococcus aureus bacterial skin contamination in health care workers.", "The active ingredient is isopropyl alcohol, which is an alcohol-based hand sanitizer.", "The active ingredients in most hand sanitizers include ethanol, benzalkonium chloride, isopropanol, alcohol, bzk, 70% ethanol and soap.", "The active ingredient in the most common hand sanitizer is ethanol, benzalkonium chloride, isopropanol, alcohol, bzk, 70% ethanol.", "While there is a new commercially available hand sanitizer using 0.12% benzalkonium chloride (BZK) as the active ingredient in hand sanitizer, most hand sanitizers are 70-80% ethanol-based or 75% isopropanol" ], "exact_answer": [ [ "Ethanol", "Alcohol" ], [ "isopropanol" ], [ "benzalkonium chloride" ], [ "methanol" ], [ "chlorhexidine" ], [ "triclosan" ] ], "type": "list", "id": "604b6a941cb411341a00016f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 220, "text": "Alcohol-based hand rubs (ABHRs) are the primary method of hand hygiene in health-care settings. ICPs increasingly are assessing ABHR product efficacy data as improved products and test methods are developed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25726133", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 388, "text": "Two ABHRs (70% ethanol) were tested according to 3 in vivo methods ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25726133", "endSection": "abstract" }, { "offsetInBeginSection": 298, "offsetInEndSection": 476, "text": " While both alcohol-based hand rubs (ABHR) or washing with soap and water are claimed to have been effective, hand sanitizers have gained more popularity due to the ease of use. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32461409", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 833, "text": "The adverse effects of alcohol in these sanitizers can be manifold. An allergic or inflammatory response can occur depending on the predisposing or preexisting conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32461409", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 350, "text": "This study was performed to evaluate the effectiveness of a new commercially available hand sanitizer using 0.12% benzalkonium chloride (BZK) as the active ingredient in reducing transient skin contamination with Staphylococcus aureus in health care workers (HCWs), as compared with the effectiveness of a 70% ethanol-based hand sanitizer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 53, "text": "benzalkonium chloride hand sanitizer ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "As a result of the coronavirus disease pandemic, commercial hand hygiene products have become scarce and World Health Organization (WHO) alcohol-based hand rub formulations containing ethanol or isopropanol are being produced for hospitals worldwide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32459621", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1062, "text": "Contrary to the originally proposed WHO hand rub formulations, both modified formulations are appropriate for surgical hand preparation after 3 minutes when alcohol concentrations of 80% wt/wt ethanol or 75% wt/wt isopropanol along with reduced glycerol concentration (0.5%) are used.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32459621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "BACKGROUND: This study was performed to evaluate the effectiveness of a new commercially available hand sanitizer using 0.12% benzalkonium chloride (BZK) as the active ingredient in reducing transient skin contamination with Staphylococcus aureus in health care workers (HCWs), as compared with the effectiveness of a 70% ethanol-based hand sanitizer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "endSection": "abstract" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1737, "text": "It was hypothesized that the active ingredient in non-alcoholic hand sanitizers, benzalkonium chloride, is responsible for the increase in fingermark development quality observed with amino acid reagents, while the increased moisture content present on the ridges resulted in better powdered fingermarks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28279942", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 307, "text": ") is a common preservative in ophthalmic medications and is the active ingredient in some skin disinfectants and hand sanitizers. BAK is known to be effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30969148", "endSection": "abstract" }, { "offsetInBeginSection": 1518, "offsetInEndSection": 1749, "text": "imary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21730079", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 855, "text": "ter the first week, the test subjects used the BZK hand sanitizer in place of the ethanol sanitizer. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32790662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "BACKGROUND: This study was performed to evaluate the effectiveness of a new commercially available hand sanitizer using 0.12% benzalkonium chloride (BZK) as the active ingredient in reducing transient skin contamination with Staphylococcus aureus in health care workers (HCWs), as compared with the effectiveness of a 70% ethanol-based hand san", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1356, "text": "nsumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of m", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32790662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Methanol as an Unlisted Ingredient in Supposedly Alcohol-Based Hand Rub Can Pose Serious Health Risk", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29987197", "endSection": "title" }, { "offsetInBeginSection": 684, "offsetInEndSection": 874, "text": "d Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32790662", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1419, "text": "One of the major problems after orthopedic surgery is delirium, with the largest number appearing after spine surgery.Conclusion: Hand sanitizer, mainly composed of ethanol, did not cause abnormal findings or interfere with the course of treatment of infectious spondylitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33134040", "endSection": "abstract" }, { "offsetInBeginSection": 2709, "offsetInEndSection": 3027, "text": "Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32790662", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 491, "text": "The purpose of this report was to present a case of ethanol-induced hand sanitizer intoxication after spine surgery in a patient with a postoperative delirious state.Presentation of case: A 63-year-old man was admitted to the spine department with intractable back pain as the main symptom and diagnosed with infectious spondylitis with discitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33134040", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 659, "text": "If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (\u226560% ethanol or \u226570% isopropanol) (2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32790662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "We investigated the charge generated on bedclothes (cotton and polyester) during bedding exchange with different humidities and the ignitability of an alcohol-based hand sanitizer (72.3 mass% ethanol) due to static spark with different temperatures to identify the hazards of electrostatic shocks and ignitions occurring previously in medical facilities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322859", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 866, "text": "We subsequently discovered the patient had consumed half of an ethanol hand sanitizer bottle (about 300-400 mL) which was placed at the foot of the bed to prevent infection transmission during the COVID-19 pandemic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33134040", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 825, "text": "Use of alcohol-based hand sanitizer is a logistically reasonable option for most circumstances, mitigating the requirement for clean running water to facilitate more traditional \"soap and water\" methods of hand disinfection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30676276", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 687, "text": "The primary outcome was alcohol-based hand sanitizer use based on weighing bottles of hand sanitizer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29502883", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 789, "text": "Comparison between hand sanitized fingermarks and non-hand sanitized fingermarks showed that the alcohol-based hand sanitizers did not result in any visible differences in fingermark quality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28279942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 729, "text": "BACKGROUND: This study was performed to evaluate the effectiveness of a new commercially available hand sanitizer using 0.12% benzalkonium chloride (BZK) as the active ingredient in reducing transient skin contamination with Staphylococcus aureus in health care workers (HCWs), as compared with the effectiveness of a 70% ethanol-based hand sanitizer.METHODS: Fingertip touch culture plates were obtained from 40 HCWs in which all HCWs used antimicrobial soap containing 0.6% chloroxylenol for handwashing according to the Centers for Disease Control and Prevention guidelines for the entire study, while continuing to use the 70% ethanol-based hand sanitizer according to the Centers for Disease Control and Prevention guideline", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 395, "text": "We evaluated the virucidal efficacy of seven hand sanitizers containing various active ingredients, such as ethanol, triclosan, and chlorhexidine, and compared their effectiveness against feline calicivirus (FCV), murine norovirus (MNV), and a GII.4 norovirus fecal extract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21219741", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 281, "text": "Benzalkonium chloride (BAK) is a common preservative in ophthalmic medications and is the active ingredient in some skin disinfectants and hand sanitizers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30969148", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 480, "text": "The goal here was to determine whether hand sanitizers that contain ethanol or isopropanol as the active microbicide might reduce transmission of these parasites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26282413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Ethanol and isopropanol in concentrations present in hand sanitizers sharply reduce excystation of Giardia and Entamoeba and eliminate oral infectivity of Giardia cysts in gerbils.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26282413", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Evaluation of a benzalkonium chloride hand sanitizer in reducing transient Staphylococcus aureus bacterial skin contamination in health care workers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668935", "endSection": "title" } ] }, { "body": "Which was the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31785606" ], "ideal_answer": [ "FTY720 (Fingolimod) was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010." ], "exact_answer": [ "FTY720", "Fingolimod" ], "type": "factoid", "id": "6053ba5b94d57fd879000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "FTY720 (Fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31785606", "endSection": "abstract" } ] }, { "body": "Which S1P receptors does fingolimod bind to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30776422" ], "ideal_answer": [ "Pharmacologically, fingolimod has been characterized as a non-selective agonist of all of the S1P receptors (S1PR), with the exception of S1P2." ], "type": "summary", "id": "6053c11094d57fd87900001a", "snippets": [ { "offsetInBeginSection": 1112, "offsetInEndSection": 1376, "text": "harmacologically, fingolimod was characterized as a non-selective agonist of all of the S1P receptors (S1PR), with the exception of S1P2, and in addition, as a selective S1P1 functional antagonist by induction of irreversible S1P1 internalization and degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30776422", "endSection": "abstract" } ] }, { "body": "What was fingolimod synthesized from?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30776422" ], "ideal_answer": [ "FTY720 (fingolimod, Gilenya\u00ae) was synthesized from myriocin, one of the metabolites of the fungus Isaria sinclairii known from traditional Chinese medicine for its antibacterial and energy boosting effect." ], "type": "summary", "id": "60550d2994d57fd87900001b", "snippets": [ { "offsetInBeginSection": 674, "offsetInEndSection": 910, "text": "Pioneering in this field was the synthesis of FTY720 (fingolimod, Gilenya\u00ae) from myriocin, one of the metabolites of the fungus Isaria sinclairii known from traditional Chinese medicine for its antibacterial and energy boosting effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30776422", "endSection": "abstract" } ] }, { "body": "What does fingolimod do to the grey matter of the brain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29938336" ], "ideal_answer": [ "Fingolimod has been shown to reduce/prevent both focal and diffuse grey matter (GM) damage in active multiple sclerosis. The percentage of patients with new cortical lesions (CL) (13.5 vs. 89%, p\u2009<\u20090.001) and the percentage of GM volume change was lower in the fingolimod treated group (p\u2009<\u20090.001). The regional analysis revealed that the treated group had also less volume loss in thalamus, caudatus, globus pallidus, cingulate cortex, and hippocampus (p\u2009<\u20090.001), as well as in, cerebellum, superior frontal gyrus, and insular-long gyrus (p\u2009<\u20090.05)." ], "type": "summary", "id": "60527fc794d57fd879000013", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 237, "text": "The mechanism of action of fingolimod within the central nervous system and its efficacy in reducing/preventing both focal and diffuse grey matter (GM) damage in active multiple sclerosis (MS) are not completely understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29938336", "endSection": "abstract" }, { "offsetInBeginSection": 1271, "offsetInEndSection": 1367, "text": "These results suggest a possible protective effect of fingolimod on focal and diffuse GM damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29938336", "endSection": "abstract" }, { "offsetInBeginSection": 706, "offsetInEndSection": 1138, "text": "At the end of the study (T24), the percentage of patients with new CLs (13.5 vs. 89%, p\u2009<\u20090.001) and the percentage of GM volume change was lower in the treated group (p\u2009<\u20090.001). The regional analysis revealed that the treated group had also less volume loss in thalamus, caudatus, globus pallidus, cingulate cortex, and hippocampus (p\u2009<\u20090.001), as well as in, cerebellum, superior frontal gyrus, and insular-long gyrus (p\u2009<\u20090.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29938336", "endSection": "abstract" } ] }, { "body": "What doses of fingolimod were administered during the FREEDOMS trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22494956" ], "ideal_answer": [ "In the FREEDOMS trial fingolimod was administered at 0.5mg or 1.25mg doses." ], "exact_answer": [ [ "0.5mg" ], [ "1.25mg" ] ], "type": "list", "id": "6052819894d57fd879000014", "snippets": [ { "offsetInBeginSection": 534, "offsetInEndSection": 866, "text": "We did subgroup analyses of ARRs (primary outcome) and confirmed disability progression (a secondary outcome) over 24 months in the FREEDOMS study, a randomised, double-blind study that included 1272 patients with relapsing-remitting MS who were assigned 1:1:1 to fingolimod (0\u00b75 mg or 1\u00b725 mg) or placebo once daily for 24 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22494956", "endSection": "abstract" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1514, "text": "Treatment with fingolimod 0\u00b75 mg was associated with significantly lower ARRs versus placebo across all subgroups except for patients aged over 40 years. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22494956", "endSection": "abstract" }, { "offsetInBeginSection": 2013, "offsetInEndSection": 2317, "text": "n patients who relapsed and had lesion activity despite treatment with interferon beta in the previous year, the ARR ratio for fingolimod 0\u00b75 mg versus placebo was 0\u00b738 (95% CI 0\u00b721-0\u00b768, p=0\u00b70011), and for treatment-naive patients with rapidly evolving severe disease it was 0\u00b733 (0\u00b718-0\u00b762, p=0\u00b70006). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22494956", "endSection": "abstract" } ] }, { "body": "How many patients were enrolled in the FREEDOMS clinical trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22494956" ], "ideal_answer": [ "FREEDOMS study, a randomised, double-blind study included 1272 patients with relapsing-remitting MS." ], "exact_answer": [ "1,272" ], "type": "factoid", "id": "605281cf94d57fd879000015", "snippets": [ { "offsetInBeginSection": 534, "offsetInEndSection": 866, "text": "We did subgroup analyses of ARRs (primary outcome) and confirmed disability progression (a secondary outcome) over 24 months in the FREEDOMS study, a randomised, double-blind study that included 1272 patients with relapsing-remitting MS who were assigned 1:1:1 to fingolimod (0\u00b75 mg or 1\u00b725 mg) or placebo once daily for 24 months. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22494956", "endSection": "abstract" } ] }, { "body": "What is blepharospasm?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14871168", "http://www.ncbi.nlm.nih.gov/pubmed/23747003", "http://www.ncbi.nlm.nih.gov/pubmed/21221669", "http://www.ncbi.nlm.nih.gov/pubmed/32091988", "http://www.ncbi.nlm.nih.gov/pubmed/32250472", "http://www.ncbi.nlm.nih.gov/pubmed/28629634", "http://www.ncbi.nlm.nih.gov/pubmed/19273924", "http://www.ncbi.nlm.nih.gov/pubmed/17986501", "http://www.ncbi.nlm.nih.gov/pubmed/31889644", "http://www.ncbi.nlm.nih.gov/pubmed/18786893", "http://www.ncbi.nlm.nih.gov/pubmed/10732662", "http://www.ncbi.nlm.nih.gov/pubmed/8098852", "http://www.ncbi.nlm.nih.gov/pubmed/19039478", "http://www.ncbi.nlm.nih.gov/pubmed/27333537", "http://www.ncbi.nlm.nih.gov/pubmed/539757", "http://www.ncbi.nlm.nih.gov/pubmed/30838249", "http://www.ncbi.nlm.nih.gov/pubmed/27064462", "http://www.ncbi.nlm.nih.gov/pubmed/16690695", "http://www.ncbi.nlm.nih.gov/pubmed/9163399", "http://www.ncbi.nlm.nih.gov/pubmed/28017248" ], "ideal_answer": [ "The neurophysiological disruptions underlying blepharospasm, a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood.", "Yes, blepharospasm is an adult-onset dystonia typically present at rest and exacerbated by bright light, stress and voluntary movements of eyes and eyelids.", "Blepharospasm is a type of focal dystonia depicted by periodic and spontaneous closure of the orbicularis oculi and surrounding muscles.", "Blepharospasm (BL) is characterized by involuntary closures of the eyelids due to spasms of the orbicularis oculi muscle.", "Blepharospasm is a type of focal dystonia. It is a movement disorder characterized by periodic and spontaneous closure of the orbicularis oculi muscle and surrounding muscles.", "Blepharospasm is a type of focal dystonia. It's a movement disorder characterized by periodic and spontaneous closure of the orbicularis oculi muscle and surrounding muscles.", "Blepharospasm is a type of focal dystonia. It's a movement disorder characterized by periodic and spontaneous closure of the orbicularis oculi and surrounding muscles.", "Blepharospasm means involuntary twitching, blinking or closure of the eyelids resulting from any cause." ], "exact_answer": [ "involuntary blinking", "increased blinking and involuntary muscle spasms of the eyelid", "involuntary closures of the eyelids", "increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood", "involuntary closures of the eyelids due to spasms of the orbicularis oculi muscle.", "movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid", "a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid" ], "type": "factoid", "id": "605256a894d57fd87900000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Blepharospasm is a type of focal dystonia depicted by periodic and spontaneous closure of the orbicularis oculi and surrounding muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31889644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Blepharospasm (BL) is characterized by involuntary closures of the eyelids due to spasms of the orbicularis oculi muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32091988", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 209, "text": ": The neurophysiological disruptions underlying blepharospasm, a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32250472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "BACKGROUND: Primary blepharospasm is a focal dystonia characterised by excessive involuntary closure of the eyelids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690695", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1080, "text": "patients with primary blepharospasm, a common form of dystonia affecting the muscles around the eyes, and 19 patients with hemifacial spasm, a facial nerve disorder causing similar eyelid spasms, completed a computerized version of the Wisconsin Card Sorting Test (cWCST). The two groups ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27333537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "The current study demonstrates that combining two mild alterations to the rat trigeminal reflex blink system reproduces the symptoms of benign essential blepharospasm, a cranial dystonia characterized by uncontrollable spasms of blinking. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9163399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Essential blepharospasm is an idiopathic disorder that consists of spontaneous, spasmodic, and involuntary eyelid closure in the absence of ocular disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19273924", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "'Benign essential blepharospasm' is a human eyelid disorder of unknown aetiology characterized by involuntary, bilateral, and disabling spasmodic contracture of the orbicularis oculi muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8098852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "BACKGROUND: Blepharospasm is a form of focal dystonia that manifests as repetitive involuntary closure of the eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23747003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Blepharospasm is a focal dystonia in which the extraocular muscles contract repetitively, leading to excessive blinking and forced eyelid closure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21221669", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 230, "text": "BACKGROUND: Blepharospasm is a focal dystonia involving chiefly the orbicularis oculi and periocular muscles resulting in involuntary sustained eyelid closure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28017248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Blepharospasm, which is the most frequent cranial dystonia, is characterized clinically by bilateral, synchronous, and symmetric involuntary orbicularis oculi muscle contractions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838249", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 692, "text": "Additional features that often characterize blepharospasm, such as increased blinking, sensory tricks that can transiently improve muscle spasms, and apraxia of eyelid opening will also be discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838249", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 116, "text": "Primary blepharospasm is a focal dystonia characterised by excessive involuntary closure of the eyelids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16690695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "INTRODUCTION: Blepharospasm is a focal dystonia characterized by involuntary cocontraction of the eyelid protractors, causing spasmodic closure o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "BACKGROUND: Blepharospasm is an adult-onset focal dystonia that causes involuntary blinking and ey", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17986501", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "BACKGROUND: Blepharospasm is a form of focal dystonia that manifests as repetitive involuntary closure ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23747003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Essential blepharospasm is a facial dystonia characterized by spontaneous, spasmodic and involuntary contractions of the eyelid muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19039478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Blepharospasm (BSP) is a rather distressing form of focal dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27064462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "BACKGROUND: Blepharospasm, the forcible closure of eyelids, is an infrequent consequence of neuroleptic treatment that, when severe, can interfere with the ability to walk, dri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10732662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Primary blepharospasm is an adult-onset focal dystonia characterised by involuntary contractions of the orbicularis oculi muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14871168", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Blepharospasm is a cranial nerve dysfunction in which involuntary and uncontrollable forcible lid closure occurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/539757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Benign essential blepharospasm is characterized by abnormal repetitive movements of lid closure and spasm of the orbiculari oculi muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18786893", "endSection": "abstract" } ] }, { "body": "Explain the action of Balovaptan.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31951127", "http://www.ncbi.nlm.nih.gov/pubmed/32935287", "http://www.ncbi.nlm.nih.gov/pubmed/31043521" ], "ideal_answer": [ "Balovaptan is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks Vasopressin-1a. It is approved for the treatment of autism spectrum disorders (ASD).", "Balovaptan is an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction.", "Balovaptan, an orally administered selective vasopressin V1a receptor antagonist which can penetrate the blood brain barrier.", "Yes, Balovaptan, an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction.", "Balovaptan is an orally administered selective vasopressin V1a receptor antagonis. Balovaptan has been evaluated for improvement of social communication and interaction.", "Balovaptan is an orally administered small molecule that binds to mTORC1 and inhibits activation of the mTOR signalling pathway. It is approved for treatment of children with autism spectrum disorders.", "Balovaptan is a low-molecular-weight, orally active, hydrophilic non-peptide dual antagonist of both the V1a and V2a receptors that is approved for the treatment of autism spectrum disorders (ASD) in children and adults with intellectual disability." ], "type": "summary", "id": "604cda0994d57fd879000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Discovery of Balovaptan, a Vasopressin 1a Receptor Antagonist for the Treatment of Autism Spectrum Disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31951127", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 160, "text": "Balovaptan, an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32935287", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 569, "text": "balovaptan, an orally administered selective vasopressin V1a receptor antagonis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31043521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "INTRODUCTION: Balovaptan, an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction, is primarily metabolized by cytochrome P450 3A4 (CYP3A4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32935287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "INTRODUCTION: Balovaptan, an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction, is primarily metabolized by cytochrome P450 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32935287", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 1058, "text": "ek clinical phase 2 study in adults with autism spectrum disorder balovaptan demonstrated improvements in Vineland-II Adaptive Behavior Scales, a secondary end point comprising communication, socialization, and daily living skills. Balovaptan ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31951127", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 208, "text": "Balovaptan, an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction, is primarily metabolized by cytochrome P450 3A4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32935287", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1046, "text": "In a 12-week clinical phase 2 study in adults with autism spectrum disorder balovaptan demonstrated improvements in Vineland-II Adaptive Behavior Scales, a secondary end point comprising communication, socialization, and daily living skills.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31951127", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 505, "text": "INTRODUCTION: Balovaptan, an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction, is primarily metabolized by cytochrome P450 3A4 (CYP3A4).METHODS: Two single-center, non-randomized, two-period, phase 1 studies assessed the effect of the strong CYP3A4 inhibitor itraconazole (study NCT03579719) or the strong CYP3A4 inducer rifampicin (study NCT03586726) at steady state on the pharmacokinetics (PK) of steady-state balovaptan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32935287", "endSection": "abstract" }, { "offsetInBeginSection": 1427, "offsetInEndSection": 1558, "text": "These results support further study of balovaptan as a potential treatment for the socialization and communication deficits in ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31043521", "endSection": "abstract" } ] }, { "body": "what is the effect of Bisphenol A in the body?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19890158", "http://www.ncbi.nlm.nih.gov/pubmed/12573901", "http://www.ncbi.nlm.nih.gov/pubmed/21705716", "http://www.ncbi.nlm.nih.gov/pubmed/12505450", "http://www.ncbi.nlm.nih.gov/pubmed/17622711", "http://www.ncbi.nlm.nih.gov/pubmed/32891999", "http://www.ncbi.nlm.nih.gov/pubmed/32777607", "http://www.ncbi.nlm.nih.gov/pubmed/22470480", "http://www.ncbi.nlm.nih.gov/pubmed/30359670", "http://www.ncbi.nlm.nih.gov/pubmed/17689037", "http://www.ncbi.nlm.nih.gov/pubmed/27089241", "http://www.ncbi.nlm.nih.gov/pubmed/25619032", "http://www.ncbi.nlm.nih.gov/pubmed/28774890", "http://www.ncbi.nlm.nih.gov/pubmed/24171222", "http://www.ncbi.nlm.nih.gov/pubmed/26821503", "http://www.ncbi.nlm.nih.gov/pubmed/32861950", "http://www.ncbi.nlm.nih.gov/pubmed/27177772", "http://www.ncbi.nlm.nih.gov/pubmed/29874946", "http://www.ncbi.nlm.nih.gov/pubmed/30257398", "http://www.ncbi.nlm.nih.gov/pubmed/27641926", "http://www.ncbi.nlm.nih.gov/pubmed/12387626", "http://www.ncbi.nlm.nih.gov/pubmed/12767684", "http://www.ncbi.nlm.nih.gov/pubmed/33049673", "http://www.ncbi.nlm.nih.gov/pubmed/33049674" ], "ideal_answer": [ "Bisphenol A (BPA) is an endocrine-disruptor compound that exhibits estrogenic activit", "BPA is considered an endocrine disruptor and several studies have proposed a relationship between exposure to BPA and the appearance of adverse health effects, such as cancer, infertility, diabetes, and obesity, among others.", "Bisphenol A is an endocrine-disruptor compound, that exhibits estrogenic activity, can affect male fertility, and can modulate the immune response to infections. It is also associated with increased risk of obesity and diabetes.", "Bisphenol A (BPA) is an endocrine disruptor that modulates the immune response to infections." ], "type": "summary", "id": "604cda2f94d57fd879000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Bisphenol A (BPA) is an endocrine-disruptor compound that exhibits estrogenic activit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33049673", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Bisphenol A (BPA), a compound used in the manufacturing of plastics and epoxy resins, is an endocrine disruptor with significant adverse impact on the human's health", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33049674", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 93, "text": "Bisphenol A (BPA) is a well-known endocrine disruptor that affects male fertility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32777607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Bisphenol A, an endocrine-disruptor compund, that modulates the immune response to infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33049673", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 243, "text": "Although the relationship between BPA exposure and increased risk of obesity and diabetes has been noted", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32891999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Bisphenols are increasingly recognized as environmental pollutants with endocrine-disrupting potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32861950", "endSection": "abstract" }, { "offsetInBeginSection": 1563, "offsetInEndSection": 1891, "text": "In conclusion, the present study using a robust experimental study design, has shown that developmental exposure to 25\u00a0\u03bcg/kg bw/day bisphenol A can cause adverse effects on fertility (decreased sperm count), neurodevelopment (masculinization of spatial learning in females) and lead to increased female body weight late in life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27089241", "endSection": "abstract" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1685, "text": "In conclusion, the adverse effect of bisphenol A on male reproduction may be due to induction of oxidative stress in sperm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12505450", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 590, "text": "Results show that Bisphenol A exposure reduced body weight and food intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641926", "endSection": "abstract" }, { "offsetInBeginSection": 199, "offsetInEndSection": 361, "text": "In this study we evaluated the effect of fetal exposure to bisphenol A, which mimics estrogenic activity, on aggressive behavior and hormonal change in male mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12573901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "By virtue of its binding to steroid hormone receptors, bisphenol A (BPA, the unconjugated bioactive monomer) is hypothesized to be estrogenic when present in sufficient quantities in the body, raising concerns that widespread exposure to BPA may impact human health. To bet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21705716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Bisphenol A [BPA, 2,2-bis(4-hydoxyphenyl)propane], an industrial chemical used in the production of polycarbonate, epoxide resin, and polyarylate, is considered to be an endocrine-disrupting chemical. BPA ma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17622711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Mal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28774890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Bisphenol A (BPA) is a small molecular weight endocrine disrupting chemical (EDC) that is used in the production of plastics with deleterious effects on various body systems while gallic acid (GA) is a known antioxidant capable of ameliorating EDC-induced perturbations. In this", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30257398", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 434, "text": "Bisphenol A may affect reproductive and neurological development; however, opinion of the European Food Safety Authority (EFSA) on bisphenol A (EFSA J, 13, 2015 and 3978) concluded that none of the available studies were robust enough to provide a point of departure for setting a tolerable daily intake for bisphenol A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27089241", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1328, "text": "The present study aimed to summarize the general effects of prenatal and postnatal Bisphenol A exposure on glucose metabolism focusing on animal studies and review the recent investigations on Bisphenol A -induced epigenetic perturbations that affect the normal glucose and lipid homeostasis and lead to type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30359670", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1495, "text": "Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29874946", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1733, "text": "This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29874946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Mesencephalic neurodegeneration in the orally administered bisphenol A-caused hyperactive rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17689037", "endSection": "title" }, { "offsetInBeginSection": 226, "offsetInEndSection": 469, "text": "Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29874946", "endSection": "abstract" }, { "offsetInBeginSection": 1359, "offsetInEndSection": 1496, "text": "Decreased intake of sweetened water was seen in females from the highest bisphenol A dose group, also a possible sign of masculinization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27089241", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 974, "text": "Decreased sperm count was found at the lowest bisphenol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27089241", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1097, "text": "Considerable data from rodent studies suggest that low doses of bisphenol A affect reproduction, lipid metabolism and neurological development, usually following intrauterine or postnatal exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171222", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 899, "text": "Some human studies suggest that bisphenol A causes coronary heart disease, increases the risk of type 2 diabetes, and has harmful effects on reproduction and development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24171222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Bisphenol A, one of the industrial chemicals used in plastics and in the coating of dishes and medical equipment, behaves as an endocrine disruptor in the human body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27177772", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Bisphenol A induces hypothalamic down-regulation of the the cannabinoid receptor 1 and anorexigenic effects in male mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641926", "endSection": "title" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1062, "text": "This observation suggests that Bisphenol A induces activation of anorexigenic signals via down-regulation of the hypothalamic cannabinoid receptor 1 with negative impact on food intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27641926", "endSection": "abstract" }, { "offsetInBeginSection": 1557, "offsetInEndSection": 1680, "text": "The results indicated that bisphenol A induces oxidative stress in the liver of rats by decreasing the antioxidant enzymes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12767684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Bisphenol A, an environmental contaminant, widely used as a monomer in polycarbonate plastics, has been shown to cause abnormalities in liver of rats and mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12767684", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 179, "text": "Bisphenol A is a weak estrogen and has been implicated as an \"endocrine disruptor\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12387626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Bisphenol A induces reactive oxygen species generation in the liver of male rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12767684", "endSection": "title" }, { "offsetInBeginSection": 278, "offsetInEndSection": 492, "text": "BPA is known for many negative effects on the human body; for instance it acts as an xenoestrogen and influences fertility and gestation and might also have carcinogenic effects, causing breast and prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26821503", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1685, "text": "In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor \u03b2 subunit.In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22470480", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 913, "text": "At a specific dose level, BPA exposure also shows oxidative toxicity and carcinogenic effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25619032", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 397, "text": "New research on very-low-dose exposure to BPA suggests an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19890158", "endSection": "abstract" } ] }, { "body": "List the main proteins found in human saliva.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30632771", "http://www.ncbi.nlm.nih.gov/pubmed/32260553", "http://www.ncbi.nlm.nih.gov/pubmed/31998446", "http://www.ncbi.nlm.nih.gov/pubmed/16440601" ], "ideal_answer": [ "Amylases\nCystatins\nImmunoglobulins\nMucins" ], "exact_answer": [ [ "Amylases" ], [ "Cystatins" ], [ "Immunoglobulins" ], [ "Mucins" ] ], "type": "list", "id": "6057238394d57fd879000029", "snippets": [ { "offsetInBeginSection": 143, "offsetInEndSection": 181, "text": "Mucins, as the major salivary proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30632771", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 769, "text": "the two thirds of identified spots corresponding to amylases, cystatins and immunoglobulins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16440601", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1014, "text": "several protein spots of immunoglobulin chains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32260553", "endSection": "abstract" }, { "offsetInBeginSection": 1595, "offsetInEndSection": 1745, "text": "The concentration of total protein and salivary amylase was significantly lower in NWS and SWS of psoriatic patients compared to the healthy control. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31998446", "endSection": "abstract" } ] }, { "body": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32913038" ], "ideal_answer": [ "No. The HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes mellitus, although not a perfect one. It is associated with high morbidity and mortality, and is not an ideal biomarker for assessment of well-controlled diabetes.", "No. HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates.", "No, HbA1c is not an ideal biomarker of well-controlled diabetes.", "No. The HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes mellitus, although not a perfect one. It is associated with poor prognosis in patients with type 2 diabetes and is an ideal biomarker for the diagnosis of Type 2 diabetes." ], "exact_answer": "no", "type": "yesno", "id": "60367f5e1cb411341a000157", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 590, "text": "HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32913038", "endSection": "abstract" } ] }, { "body": "Which tool has been developed for microRNA-target enrichment and network-based analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31684860" ], "ideal_answer": [ "MIENTURNET (MicroRNA ENrichment TURned NETwork) is a web tool that receives in input a list of miRNAs or mRNAs and tackles the problem of prioritizing miRNA-target interactions by performing a statistical analysis followed by a fully featured network-based visualization and analysis. The statistics is used to assess the significance of an over-representation of miRNA-target interactions and then MIENTURNET filters based on the statistical significance associated with each miRNA-target interaction. In addition, the holistic approach of the network theory is used to infer possible evidences of miRNA regulation by capturing emergent properties of the miRNA-target regulatory network that would be not evident through a pairwise analysis of the individual components.", "MIENTURNET (MicroRNA ENrichment TURned NETwork) is an interactive web tool for microRNA-target enrichment and network-based analysis.", "MIENTURNET is a web tool for microRNA-target enrichment and network-based analysis. MIENTURNET offers the possibility to consistently perform both statistical and network-based analyses." ], "exact_answer": [ "MIENTURNET" ], "type": "factoid", "id": "60579cb394d57fd87900002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "MIENTURNET: an interactive web tool for microRNA-target enrichment and network-based analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31684860", "endSection": "title" }, { "offsetInBeginSection": 563, "offsetInEndSection": 2057, "text": "We propose a new and easy-to-use web tool MIENTURNET (MicroRNA ENrichment TURned NETwork) that receives in input a list of miRNAs or mRNAs and tackles the problem of prioritizing miRNA-target interactions by performing a statistical analysis followed by a fully featured network-based visualization and analysis. The statistics is used to assess the significance of an over-representation of miRNA-target interactions and then MIENTURNET filters based on the statistical significance associated with each miRNA-target interaction. In addition, the holistic approach of the network theory is used to infer possible evidences of miRNA regulation by capturing emergent properties of the miRNA-target regulatory network that would be not evident through a pairwise analysis of the individual components.CONCLUSION: MIENTURNET offers the possibility to consistently perform both statistical and network-based analyses by using only a single tool leading to a more effective prioritization of the miRNA-target interactions. This has the potential to avoid researchers without computational and informatics skills to navigate multiple websites and thus to independently investigate miRNA activity in every cellular process of interest in an easy and at the same time exhaustive way thanks to the intuitive web interface. The web application along with a well-documented and comprehensive user guide are freely available at http://userver.bio.uniroma1.it/apps/mienturnet/ without any login requirement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31684860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "MIENTURNET: an interactive web tool for microRNA-target enrichment and network-based analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31684860", "endSection": "title" }, { "offsetInBeginSection": 554, "offsetInEndSection": 875, "text": "RESULTS: We propose a new and easy-to-use web tool MIENTURNET (MicroRNA ENrichment TURned NETwork) that receives in input a list of miRNAs or mRNAs and tackles the problem of prioritizing miRNA-target interactions by performing a statistical analysis followed by a fully featured network-based visualization and analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31684860", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 854, "text": " processes. A reasonable solution is certainly to prioritize miRNA-target interactions to maximize the effectiveness of the downstream analysis.RESULTS: We propose a new and easy-to-use web tool MIENTURNET (MicroRNA ENrichment TURned NETwork) that receives in input a list of miRNAs or mRNAs and tackles the problem of prioritizing miRNA-target interactions by performing a statistical analysis followed by a fully featured network-based visual", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31684860", "endSection": "abstract" }, { "offsetInBeginSection": 1073, "offsetInEndSection": 1547, "text": "-target interaction. In addition, the holistic approach of the network theory is used to infer possible evidences of miRNA regulation by capturing emergent properties of the miRNA-target regulatory network that would be not evident through a pairwise analysis of the individual components.CONCLUSION: MIENTURNET offers the possibility to consistently perform both statistical and network-based analyses by using only a single tool leading to a more effective prioritization ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31684860", "endSection": "abstract" } ] }, { "body": "List example genes that SWIM tool has identified and which are down-regulated in glioblastoma", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30497369" ], "ideal_answer": [ "SWIM is a software able to unveil a small pool of genes - called switch genes - critically associated with drastic changes in cell phenotype. Applying SWIM to the expression profiling of glioblastoma stem-like cells and conventional glioma cell lines identifies switch genes related to stem-like phenotype. SWIM identifies 171 switch genes that are all down-regulated in glioblastoma stem-like cells. This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in \"ECM-receptor interaction\" and \"focal adhesion\" pathways.", "This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in \"ECM-receptor interaction\" and \"focal adhesion\" pathways.", "SWIM tool has identified and which genes are down-regulated in glioblastoma. These include the genes: itga3, hmmr, sox2, cav1, itga5, thbs1, sdc1, col6a3, col5a1 and sall2.", "SWIM tool has identified and which genes are down-regulated in glioblastoma and which are important for tumorigenesis: met, vegfc, flnb, itga3, hmmr, sox2, cav1, itGA5, thbs1, sdc1, col6a3, col5a1 and sall2.", "SWIM identifies 171 switch genes that are all down-regulated in glioblastoma stem-like cells. This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in \"ECM-receptor interaction\" and \"focal adhesion\" pathways" ], "exact_answer": [ [ "CAV1" ], [ "COL5A1" ], [ "COL6A3" ], [ "FLNB" ], [ "HMMR" ], [ "ITGA3" ], [ "ITGA5" ], [ "MET" ], [ "SDC1" ], [ "THBS1" ], [ "VEGFC" ] ], "type": "list", "id": "6057a1ed94d57fd87900002f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 1216, "text": "It is well-known that glioblastoma contains self-renewing, stem-like subpopulation with the ability to sustain tumor growth. These cells - called cancer stem-like cells - share certain phenotypic characteristics with untransformed stem cells and are resistant to many conventional cancer therapies, which might explain the limitations in curing human malignancies. Thus, the identification of genes controlling the differentiation of these stem-like cells is becoming a successful therapeutic strategy, owing to the promise of novel targets for treating malignancies.METHODS: Recently, we developed SWIM, a software able to unveil a small pool of genes - called switch genes - critically associated with drastic changes in cell phenotype. Here, we applied SWIM to the expression profiling of glioblastoma stem-like cells and conventional glioma cell lines, in order to identify switch genes related to stem-like phenotype.RESULTS: SWIM identifies 171 switch genes that are all down-regulated in glioblastoma stem-like cells. This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in \"ECM-receptor interaction\" and \"focal adhesion\" pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30497369", "endSection": "abstract" } ] }, { "body": "Describe SWItchMiner (SWIM)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28317894" ], "ideal_answer": [ "SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called \"fight-club hubs\", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called \"switch genes\", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance.", "SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. SWIM allows unearthing the existence of a new class of hubs, called \"fight-club hubs\", characterized by a marked negative correlation with their first nearest neighbors." ], "type": "summary", "id": "6057a3bf94d57fd879000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "SWIM: a computational tool to unveiling crucial nodes in complex biological networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28317894", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1354, "text": "SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called \"fight-club hubs\", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called \"switch genes\", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28317894", "endSection": "abstract" } ] }, { "body": "What promotes amyloid-peptide beta 42 (A\u03b242) accumulation in neuroblastoma cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27476701" ], "ideal_answer": [ "The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer's disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients' brain. A specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (A\u03b242) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis.", "The amyloid-peptide beta 42 (A\u03b242) accumulates in neuroblastoma cells due to a protein called apoE4-165, which is an apolipoprotein (APOE4). This protein is the most common protein responsible for late-onset Alzheimer disease." ], "exact_answer": [ "apoE4-165" ], "type": "factoid", "id": "6057bf0694d57fd879000031", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 798, "text": "The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer's disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients' brain. We have previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (A\u03b242) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis. Here, we show that these effects are allele-dependent and absolutely require the apoE4 background. Furthermore, the exact length of the fragment is critical since longer or shorter length carboxyl-terminal truncated apoE4 forms do not elicit the same effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27476701", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 537, "text": "We have previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (A\u03b242) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27476701", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 547, "text": "e previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (A\u03b242) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis. Here, we ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27476701", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1237, "text": " to other allelic backgrounds, apoE4-165 is structurally distinct and less thermodynamically stable suggesting that the combination of a well-folded structure with structural plasticity is a unique characteristic of this fragment. Overall, our fi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27476701", "endSection": "abstract" } ] }, { "body": "Which method has been developed for detection of ATAC-seq or ChIP-seq signals with DNA methylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31752933" ], "ideal_answer": [ "EpiMethylTag is a fast, low- input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA.", "EpiMethyl tag is a method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA.", "Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or transcription factor (TF) binding if assays are performed separately. EpiMethylTag is a fast, low-input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA.", "EpiMethyl tag is a fast, low- input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA.", "EpiMethylTag is a fast, low- input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion to simultaneously examine accessibility/TF binding and methylation on the same DNA.", "EpiMethyl tag is a technology that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." ], "exact_answer": [ "EpiMethylTag" ], "type": "factoid", "id": "6057c2f894d57fd879000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "EpiMethylTag: simultaneous detection of ATAC-seq or ChIP-seq signals with DNA methylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752933", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 686, "text": "Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or transcription factor (TF) binding if assays are performed separately. We developed a fast, low-input, low sequencing depth method, EpiMethylTag, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA. Here we demonstrate that EpiMethylTag can be used to study the functional interplay between chromatin accessibility and TF binding (CTCF and KLF4) at methylated sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752933", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 518, "text": "We developed a fast, low-input, low sequencing depth method, EpiMethylTag, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752933", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 529, "text": "veloped a fast, low-input, low sequencing depth method, EpiMethylTag, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA. Here we de", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "EpiMethylTag: simultaneous detection of ATAC-seq or ChIP-seq signals with DNA methylation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752933", "endSection": "title" } ] }, { "body": "Which protein is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31548608" ], "ideal_answer": [ "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks.", "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks. Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in enhancer connectivity.", "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancers networks.", "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks. How transcription factors orchestrate the complex molecular changes around their target gene loci remains incompletely understood.", "KLF4 is involved in the organization and regulation of pluripotency-associated enhancer networks. How transcription factors orchestrate the complex molecular changes around their target gene loci remains incompletely understood." ], "exact_answer": [ "KLF4" ], "type": "factoid", "id": "6057c78994d57fd879000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31548608", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 968, "text": "Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors, as is exemplified by reprogramming somatic cells to pluripotent stem cells through the expression of OCT4, KLF4, SOX2 and cMYC. How transcription factors orchestrate the complex molecular changes around their target gene loci remains incompletely understood. Here, using KLF4 as a paradigm, we provide a transcription-factor-centric view of chromatin reorganization and its association with three-dimensional enhancer rewiring and transcriptional changes during the reprogramming of mouse embryonic fibroblasts to pluripotent stem cells. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in enhancer connectivity, whereas disruption of individual KLF4 binding sites within pluripotent-stem-cell-specific enhancers was sufficient to impair enhancer-promoter contacts and reduce the expression of associated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31548608", "endSection": "abstract" } ] }, { "body": "Where is the agouti-related peptide expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31974377", "http://www.ncbi.nlm.nih.gov/pubmed/31557134", "http://www.ncbi.nlm.nih.gov/pubmed/31995643", "http://www.ncbi.nlm.nih.gov/pubmed/31692367" ], "ideal_answer": [ "Function. Agouti-related protein is expressed primarily in the adrenal gland, subthalamic nucleus, and hypothalamus, with lower levels of expression in the testis, kidneys, and lungs.", "The agouti-related peptide is expressed in neurons in the hypothalamus." ], "exact_answer": [ "in the Hypothalamus" ], "type": "factoid", "id": "60578f2894d57fd87900002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Activation of Agouti-Related Peptide (AgRP)-expressing neurons promotes feeding and insulin resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31974377", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 185, "text": "Within the ventral hypothalamus (VHT), the orexigenic neurons co-express Agouti-related peptide (AgRP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31995643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Arcuate nucleus agouti-related peptide (AgRP) neurons play a central role in feeding and are under complex regulation by both homeostatic hormonal and nutrient signals and hypothalamic neuronal pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31557134", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1143, "text": "hypothalamic neuropeptides [neuropeptide Y (npy), agouti-related protein 1 (agrp1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692367", "endSection": "abstract" } ] }, { "body": "What is the function of ketohexokinase-A?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27088854", "http://www.ncbi.nlm.nih.gov/pubmed/31750240", "http://www.ncbi.nlm.nih.gov/pubmed/26083752", "http://www.ncbi.nlm.nih.gov/pubmed/29604362" ], "ideal_answer": [ "The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C." ], "exact_answer": [ "Ketohexokinase is the central fructose-metabolising enzyme" ], "type": "factoid", "id": "60578bc994d57fd87900002b", "snippets": [ { "offsetInBeginSection": 132, "offsetInEndSection": 320, "text": "The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26083752", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 651, "text": "HK-A acts as a protein kinase, phosphorylating and activating phosphoribosyl pyrophosphate synthetase 1 (PRPS1) to promote pentose phosphate pathway-dependent de novo nucleic acid synthesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27088854", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 116, "text": "Ketohexokinase (KHK), a primary enzyme in fructose metabolism, has two isoforms, namely, KHK-A and KHK-C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29604362", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 187, "text": "The metabolism-reprogramming marker ketohexokinase (KHK)-A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31750240", "endSection": "abstract" } ] }, { "body": "Are the major royal jelly proteins similar to the yellow proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15037093", "http://www.ncbi.nlm.nih.gov/pubmed/10772900" ], "ideal_answer": [ "Yes,\nMajor royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family." ], "exact_answer": "yes", "type": "yesno", "id": "6057003594d57fd879000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Major royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15037093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Analysis of Drosophila yellow-B cDNA reveals a new family of proteins related to the royal jelly proteins in the honeybee", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10772900", "endSection": "title" }, { "offsetInBeginSection": 586, "offsetInEndSection": 705, "text": "he Yellow proteins are related to the Royal Jelly proteins and have no relatives in other non-insect metazoan species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10772900", "endSection": "abstract" } ] }, { "body": "Which R packages have been developed for studying TADs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "http://www.ncbi.nlm.nih.gov/pubmed/32211023" ], "ideal_answer": [ "TADCompare is an R Package for differential and temporal analysis of Topologically Associated Domains. SpectralTAD is an R package for defining a hierarchy of topologically associated domains using spectral clustering.", "TADCompare is a method for differential analysis of boundaries of interacting domains between two or more Hi-C datasets. SpectralTAD is a method for defining a hierarchy of topologically associated domains using spectral clustering." ], "exact_answer": [ [ "TADCompare" ], [ "SpectralTAD" ] ], "type": "list", "id": "60607fea94d57fd87900003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "TADCompare: An R Package for Differential and Temporal Analysis of Topologically Associated Domains.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32211023", "endSection": "title" }, { "offsetInBeginSection": 556, "offsetInEndSection": 1344, "text": "We developed TADCompare, a method for differential analysis of boundaries of interacting domains between two or more Hi-C datasets. TADCompare is based on a spectral clustering-derived measure called the eigenvector gap, which enables a loci-by-loci comparison of boundary differences. Using this measure, we introduce methods for identifying differential and consensus boundaries of interacting domains and tracking boundary changes over time. We further propose a novel framework for the systematic classification of boundary changes. Colocalization- and gene enrichment analysis of different types of boundary changes demonstrated distinct biological functionality associated with them. TADCompare is available on https://github.com/dozmorovlab/TADCompare and Bioconductor (submitted).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32211023", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "SpectralTAD: an R package for defining a hierarchy of topologically associated domains using spectral clustering.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "endSection": "title" }, { "offsetInBeginSection": 740, "offsetInEndSection": 1494, "text": "Our method, implemented in an R package, SpectralTAD, detects hierarchical, biologically relevant TADs, has automatic parameter selection, is robust to sequencing depth, resolution, and sparsity of Hi-C data. SpectralTAD outperforms four state-of-the-art TAD callers in simulated and experimental settings. We demonstrate that TAD boundaries shared among multiple levels of the TAD hierarchy were more enriched in classical boundary marks and more conserved across cell lines and tissues. In contrast, boundaries of TADs that cannot be split into sub-TADs showed less enrichment and conservation, suggesting their more dynamic role in genome regulation.CONCLUSION: SpectralTAD is available on Bioconductor, http://bioconductor.org/packages/SpectralTAD/ .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 952, "text": "LTS: Our method, implemented in an R package, SpectralTAD, detects hierarchical, biologically relevant TADs, has automatic parameter selection, is robust to sequencing depth, resolution, and sparsity of Hi-C data. Spe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "TADCompare: An R Package for Differential and Temporal Analysis of Topologically Associated Domains", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32211023", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "SpectralTAD: an R package for defining a hierarchy of topologically associated domains using spectral clustering", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "endSection": "title" }, { "offsetInBeginSection": 567, "offsetInEndSection": 698, "text": "d TADCompare, a method for differential analysis of boundaries of interacting domains between two or more Hi-C datasets. TADCompare", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32211023", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 950, "text": "r method, implemented in an R package, SpectralTAD, detects hierarchical, biologically relevant TADs, has automatic parameter selection, is robust to sequencing depth, resolution, and sparsity of Hi-C data. S", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 918, "text": "regulation. Existing tools for TAD calling are frequently sensitive to biases in Hi-C data, depend on tunable parameters, and are computationally inefficient.METHODS: To address these challenges, we developed a novel sliding window-based spectral clustering framework that uses gaps between consecutive eigenvectors for TAD boundary identification.RESULTS: Our method, implemented in an R package, SpectralTAD, detects hierarchical, biologically relevant TADs, has automatic parameter selection, is robust to sequencing depth, resoluti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1452, "text": "cross cell lines and tissues. In contrast, boundaries of TADs that cannot be split into sub-TADs showed less enrichment and conservation, suggesting their more dynamic role in genome regulation.CONCLUSION: SpectralTAD is available on Bioconductor, http:", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32689928", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 687, "text": "We developed TADCompare, a method for differential analysis of boundaries of interacting domains between two or more Hi-C datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32211023", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 841, "text": "TADCompare is based on a spectral clustering-derived measure called the eigenvector gap, which enables a loci-by-loci comparison of boundary differences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32211023", "endSection": "abstract" } ] }, { "body": "Which bioconductor tool has been developed for accessing bacterial regulatory networks?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32573705" ], "ideal_answer": [ "The Regutools R package to facilitates programmatic access to RegulonDB data in computational biology. regutools gives researchers the possibility of writing reproducible workflows with automated queries to RegulonDB. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages.", "RegulonDB has collected, harmonized and centralized data from hundreds of experiments for nearly two decades and is considered a point of reference for transcriptional regulation in Escherichia coli K12. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages." ], "exact_answer": [ "regutools" ], "type": "factoid", "id": "606081e594d57fd879000041", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Programmatic access to bacterial regulatory networks with regutools.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32573705", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1076, "text": "RegulonDB has collected, harmonized and centralized data from hundreds of experiments for nearly two decades and is considered a point of reference for transcriptional regulation in Escherichia coli K12. Here, we present the regutools R package to facilitate programmatic access to RegulonDB data in computational biology. regutools gives researchers the possibility of writing reproducible workflows with automated queries to RegulonDB. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages. We demonstrate the integration of regutools with Bioconductor by analyzing transcription factor DNA binding sites and transcriptional regulatory networks from RegulonDB. We anticipate that regutools will serve as a useful building block in our progress to further our understanding of gene regulatory networks.AVAILABILITY AND IMPLEMENTATION: regutools is an R package available through Bioconductor at bioconductor.org/packages/regutools.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32573705", "endSection": "abstract" } ] }, { "body": "Is the Apis mellifera genome available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32384687", "http://www.ncbi.nlm.nih.gov/pubmed/32518251", "http://www.ncbi.nlm.nih.gov/pubmed/31965987", "http://www.ncbi.nlm.nih.gov/pubmed/32134461" ], "ideal_answer": [ "Yes,\nthe Apis mellifera genome is available since 2006." ], "exact_answer": "yes", "type": "yesno", "id": "6057014c94d57fd879000022", "snippets": [ { "offsetInBeginSection": 1204, "offsetInEndSection": 1343, "text": " Mining Apis mellifera sequences made it possible to identify the honey bee subspecies both at the mitochondrial and nuclear genome levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32518251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Honey bee research is believed to be influenced dramatically by colony collapse disorder (CCD) and the sequenced genome release in 2006, but this assertion has never been tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32384687", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 844, "text": " The genome release and CCD had quantitively only minor effects, mainly on honey bee health-related topics post-2006. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32384687", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 709, "text": "We show that the honeybee genome is structured with respect to plasticity; genes that respond to an environmental trigger are colocated in the honeybee genome in a series of gene clusters, many of which have been assembled in the last 80 My during the evolution of the Apidae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32134461", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 750, "text": "we have mined histone methyltransferases and demethylases from the whole genome sequence of Aedes aegypti (Diptera), the pea aphid Acyrthosiphon pisum, the triatomid bug Rhodnius prolixus (Hemiptera), the honeybee Apis mellifera (Hymenoptera),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31965987", "endSection": "abstract" } ] }, { "body": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8855341", "http://www.ncbi.nlm.nih.gov/pubmed/23113340", "http://www.ncbi.nlm.nih.gov/pubmed/18974556", "http://www.ncbi.nlm.nih.gov/pubmed/31669315", "http://www.ncbi.nlm.nih.gov/pubmed/10215406", "http://www.ncbi.nlm.nih.gov/pubmed/27415035", "http://www.ncbi.nlm.nih.gov/pubmed/32129495", "http://www.ncbi.nlm.nih.gov/pubmed/22197188", "http://www.ncbi.nlm.nih.gov/pubmed/25438602", "http://www.ncbi.nlm.nih.gov/pubmed/12021248", "http://www.ncbi.nlm.nih.gov/pubmed/26510092", "http://www.ncbi.nlm.nih.gov/pubmed/32270509", "http://www.ncbi.nlm.nih.gov/pubmed/21204798", "http://www.ncbi.nlm.nih.gov/pubmed/9392583", "http://www.ncbi.nlm.nih.gov/pubmed/25088311" ], "ideal_answer": [ "The gene encoding clcn1, mBNl1, gcic-1, scn4a, clc-1 and dmpk are implicated in myotonic goats and other nondystrophic myotonias.", "The following genes are implicated in myotonic goats and other nondystrophic myotonias: clcn1 (also known as mbnl1), gcic-1, scn4a, clc-1 and dmpk.", "The genes that are implicated in myotonic goats and other nondystrophic myotonias are clcn1, mbnl1, gcic-1, scn4a, clc-1 and dmpk.", "Myotonic goats and other Nondystrophic myotonic myotonias are caused by mutations in either the CLCN1 gene or the SCN4A gene.", "The gene encoding clcn1 (also known as clc-1), gcic-1, scn4a, and dmpk is implicated in myotonic goats and other nondystrophic myotonias", "The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. In goats, the gCIC-1 protein encoded by the CLCN1 gene, is affected .", "The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene", "The gene encoding clcn1, mphanl1, gcic-1, scn4a, clc-1 and dmpk are implicated in myotonic goats and other nondystrophic myotonias", "Myotonic goats and other Nondystrophic Myotonias are caused by mutations in either the CLCN1 gene in Myotonia congenita or in the SCN4A gene in S4A." ], "exact_answer": [ [ "gCIC-1 protein encoding gene" ], [ "CLCN1" ], [ "SCN4A" ], [ "mbnl1" ], [ "dmpk" ], [ "CCHC-type zinc finger" ] ], "type": "list", "id": "605255a894d57fd87900000a", "snippets": [ { "offsetInBeginSection": 204, "offsetInEndSection": 594, "text": "We have investigated the molecular basis for decreased muscle chloride conductance in the myotonic goat, an historically important animal model for the elucidation of the role of chloride in muscle excitation. A single nucleotide change causing the substitution of proline for a conserved alanine residue in the carboxyl terminus of the goat muscle chloride channel (gCIC-1) was discovered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8855341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32270509", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 227, "text": "he observed phenotype resembled congenital myotonia caused by CLCN1 mutations in goats and humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Nondystrophic myotonias are characterized by muscle stiffness triggered by voluntary movement. They are caused by mutations in either the CLCN1 gene in myotonia congenita or in the SCN4A gene in paramyotonia congenita and sodium channel myotonias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25088311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Thomsen's and Becker's diseases are the most prevalent nondystrophic myotonias. Their frequency varies, according to different sources, from 1 : 100 000 to 1 : 10 000. Thomsen's myotonia is autosomal dominant, and Becker's myotonia is autosomal recessive. Both diseases result from mutations of the CLCN1 gene encoding chloride ion channels of skeletal muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23113340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Thomsen's (TM) and Becker's (BM) Myotonias are nondystrophic myotonias. At present, 150 mutations in the CLCN1 gene, which results in the development of TM and BM, have been described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25438602", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 505, "text": " Based on the results of a molecular-genetic analysis of CLCN1 gene in patients with nondystrophic myotonias,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25438602", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 380, "text": "Mutations in the genes encoding chloride (ClC-1) or sodium (SCN4A) channels expressed exclusively in skeletal muscle cause nondystrophic myotonias. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974556", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 379, "text": "Mutations in the genes encoding chloride (ClC-1) or sodium (SCN4A) channels expressed exclusively in skeletal muscle cause nondystrophic myotonias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "INTRODUCTION: Mutations of the voltage-gated sodium channel gene (SCN4A), which encodes Nav1.4, cause nondystrophic myotonia that occasionally is associated with severe apnea and lary", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32129495", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 388, "text": "ations in the genes encoding chloride (ClC-1) or sodium (SCN4A) channels expressed exclusively in skeletal muscle cause nondystrophic myotonias. Genetic ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Nondystrophic myotonias are disorders of Na+ (Nav1.4 or SCN4A) and Cl- (CLCN1) channels in skeletal muscles, and frequently show phenotype heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31669315", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 863, "text": "Currently, four genes are identified to be involved in myotonia: the muscle voltage-gated sodium and chloride channel genes SCN4A and CLCN1, the myotonic dystrophy protein kinase (DMPK) gene, and the CCHC-type zinc finger, nucleic acid binding protein gene CNBP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21204798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Mutations in the skeletal muscle voltage-gated sodium channel alpha-subunit gene (SCN4A) have been associated with a spectrum of inherited nondystrophic myotonias and periodic paralyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9392583", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 728, "text": "Myotonic dystrophy Type 1 is caused by CTG repeat expansion in the 3' untranslated region in the Dystrophia Myotonica Protein Kinase (DMPK) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18974556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510092", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32270509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "INTRODUCTION: Mutations of the voltage-gated sodium channel gene (SCN4A), which encodes Nav1.4, cause nondystrophic myotonia that occasionally is associated with severe apnea and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32129495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Becker syndrome, a recessive nondystrophic myotonia caused by mutations in the chloride channel 1 gene (CLCN1), is characterized by delayed muscle relaxation after contraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12021248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Autosomal dominant myotonia congenita or Thomsen's disease and autosomal recessive myotonia congenita or Becker's are rare nondystrophic disorders due to allelic mutations of the muscle chloride channel gene, CLCN1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10215406", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 745, "text": "Therefore we analyzed genetic mutations in CLCN1 and SCN4A in 10 Chinese families clinically diagnosed with Non-dystrophic myotonias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27415035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Sequence CLCN1 and SCN4A in patients with Nondystrophic myotonias in Chinese populations: Genetic and pedigree analysis of 10 families and review of the literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27415035", "endSection": "title" } ] }, { "body": "Has the olive tree pollen proteome been studied?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31192604" ], "ideal_answer": [ "Yes,\nOlive pollen is a major allergenic source worldwide due to its extensive cultivation. We have combined available genomics data with a comprehensive proteomics approach to get the annotated olive tree (Olea europaea L.) pollen proteome and define its complex allergenome." ], "exact_answer": "yes", "type": "yesno", "id": "60570af094d57fd879000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Olive pollen is a major allergenic source worldwide due to its extensive cultivation. We have combined available genomics data with a comprehensive proteomics approach to get the annotated olive tree (Olea europaea L.) pollen proteome and define its complex allergenome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31192604", "endSection": "abstract" } ] }, { "body": "Is cadherin a plasma membrane marker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31838186", "http://www.ncbi.nlm.nih.gov/pubmed/32044971", "http://www.ncbi.nlm.nih.gov/pubmed/32939719", "http://www.ncbi.nlm.nih.gov/pubmed/32239671" ], "ideal_answer": [ "Yes,\ncadherin is a plasma membrane protein marker." ], "exact_answer": "yes", "type": "yesno", "id": "6060c7c094d57fd879000046", "snippets": [ { "offsetInBeginSection": 966, "offsetInEndSection": 1010, "text": "the plasma membrane-bound E-cadherin protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32939719", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1013, "text": "VE-cadherin protein levels were also increased in the plasma membrane fraction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31838186", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 698, "text": " recycling of VE-cadherin to the plasma membrane,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32044971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "E-cadherin, a central component of the adherens junction (AJ), is a single-pass transmembrane protein ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32239671", "endSection": "abstract" } ] }, { "body": "What impacts stability of genomic imprinting in mouse pluripotent stem cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32187532" ], "ideal_answer": [ "A susceptibility locus on chromosome 13 profoundly impacts the stability of genomic imprinting in mouse pluripotent stem cells." ], "exact_answer": [ "a susceptibility locus on chromosome 13" ], "type": "factoid", "id": "6057c0cd94d57fd879000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A Susceptibility Locus on Chromosome 13 Profoundly Impacts the Stability of Genomic Imprinting in Mouse Pluripotent Stem Cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32187532", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 911, "text": "Cultured pluripotent cells accumulate detrimental chromatin alterations, including DNA methylation changes at imprinted genes known as loss of imprinting (LOI). Although the occurrence of LOI is considered a stochastic phenomenon, here we document a genetic determinant that segregates mouse pluripotent cells into stable and unstable cell lines. Unstable lines exhibit hypermethylation at Dlk1-Dio3 and other imprinted loci, in addition to impaired developmental potential. Stimulation of demethylases by ascorbic acid prevents LOI and loss of developmental potential. Susceptibility to LOI greatly differs between commonly used mouse strains, which we use to map a causal region on chromosome 13 with quantitative trait locus (QTL) analysis. Our observations identify a strong genetic determinant of locus-specific chromatin abnormalities in pluripotent cells and provide a non-invasive way to suppress them. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32187532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "A Susceptibility Locus on Chromosome 13 Profoundly Impacts the Stability of Genomic Imprinting in Mouse Pluripotent Stem Cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32187532", "endSection": "title" } ] }, { "body": "What are the end products of the shikimate pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32616740", "http://www.ncbi.nlm.nih.gov/pubmed/31961458", "http://www.ncbi.nlm.nih.gov/pubmed/32154231", "http://www.ncbi.nlm.nih.gov/pubmed/32642925", "http://www.ncbi.nlm.nih.gov/pubmed/32538627" ], "ideal_answer": [ "The shikimate pathway responsible for the generation of aromatic amino acids" ], "exact_answer": [ "aromatic amino acids" ], "type": "factoid", "id": "6057057c94d57fd879000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The shikimate pathway is indispensable for the biosynthesis of natural products with aromatic moieties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32642925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "In plants, the shikimate pathway generally occurs in plastids and leads to the biosynthesis of aromatic amino acids. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32616740", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 281, "text": "the shikimate pathway responsible for the generation of aromatic amino acids", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32538627", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 797, "text": "Microorganisms are able to synthesize aromatic amino acids through the shikimate pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32154231", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 197, "text": "aromatic amino acid synthesis via the shikimate pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31961458", "endSection": "abstract" } ] }, { "body": "What are the uber-operons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16682449" ], "ideal_answer": [ "Uber-operons are groups of functionally or transcriptionally related operons, whose gene sets are conserved across multiple reference genomes. Many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments." ], "type": "summary", "id": "5e9ef62f0d431b5f73000006", "snippets": [ { "offsetInBeginSection": 233, "offsetInEndSection": 525, "text": "Uber-operons represent a rich set of footprints of operon evolution, whose full utilization could lead to new and more powerful tools for elucidation of biological pathways and networks than what operons have provided, and a better understanding of prokaryotic genome structures and evolution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682449", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 733, "text": "uber-operons through identifying groups of functionally or transcriptionally related operons, whose gene sets are conserved across the target and multiple reference genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682449", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1157, "text": "many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682449", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 734, "text": "Our prediction algorithm predicts uber-operons through identifying groups of functionally or transcriptionally related operons, whose gene sets are conserved across the target and multiple reference genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "We present a study on computational identification of uber-operons in a prokaryotic genome, each of which represents a group of operons that are evolutionarily or functionally associated through operons in other (reference) genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682449", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1172, "text": "r, we predicted 158 uber-operons in Escherichia coli K12 covering 1830 genes, and found that many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments. For some of th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682449", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 526, "text": "Uber-operons represent a rich set of footprints of operon evolution, whose full utilization could lead to new and more powerful tools for elucidation of biological pathways and networks than what operons have provided, and a better understanding of prokaryotic genome structures and evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16682449", "endSection": "abstract" } ] }, { "body": "Which key gene is involved in syndromic obesity phenotype of patients with 1p21.3 microdeletions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "http://www.ncbi.nlm.nih.gov/pubmed/22003227" ], "ideal_answer": [ "MIR137 is the key gene mediator of the syndromic obesity phenotype of patients with 1p21. 3 microdeletions.", "MIR137 is the key gene mediator of the syndromic obesity phenotype of patients with 1p21.3 microdeletions.", "The MIR137 gene. It is the one that is responsible for the obesity phenotype of patients with 1p21.3 microdeletions.", "The MIR137 gene. It is the one that is responsible for the obesity phenotype of patients carrying 1p21.3 microdeletions.", "Deletions in the long arm of chromosome 1 have been described in patients with a phenotype consisting primarily of obesity, intellectual disability and autism-spectrum disorder. MIR137 is suggested as the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions." ], "exact_answer": [ "MIR137" ], "type": "factoid", "id": "6031270b1cb411341a00012c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 552, "text": "Deletions in the long arm of chromosome 1 have been described in patients with a phenotype consisting primarily of obesity, intellectual disability and autism-spectrum disorder. The minimal region of overlap comprises two genes: DPYD and MIR137.CASE PRESENTATION: We describe a 10-year-old boy with syndromic obesity who carries a novel 1p21.3\u00a0deletion overlapping the critical region with the MIR137 gene only.CONCLUSIONS: This study suggests that MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 1637, "offsetInEndSection": 1838, "text": "CONCLUSIONS: This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 425, "text": "e describe a 10-year-old boy with syndromic obesity who carries a novel 1p21.3\u00a0deletion overlapping the critical region with the MIR137 gene only.CO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27822311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22003227", "endSection": "title" } ] }, { "body": "Is cabergoline used for treatment of the Nelson's syndrome ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20702648", "http://www.ncbi.nlm.nih.gov/pubmed/10971110", "http://www.ncbi.nlm.nih.gov/pubmed/15557761", "http://www.ncbi.nlm.nih.gov/pubmed/26221547", "http://www.ncbi.nlm.nih.gov/pubmed/16845600", "http://www.ncbi.nlm.nih.gov/pubmed/16311416", "http://www.ncbi.nlm.nih.gov/pubmed/17574308", "http://www.ncbi.nlm.nih.gov/pubmed/10710275" ], "ideal_answer": [ "Yes, cabergoline has been shown to be effective for treatment of the Nelson's syndrome." ], "exact_answer": "yes", "type": "yesno", "id": "601c4e5e1cb411341a000021", "snippets": [ { "offsetInBeginSection": 890, "offsetInEndSection": 1051, "text": "Due to a rapid regrowth of the tumour, the patient did not receive gamma-knife therapy and was treated with cabergoline and somatostatin analogue for some time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26221547", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 304, "text": "Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's disease (CD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702648", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 611, "text": " In our observation cabergoline at 2 mg per week seems to be efficient after a 3 and a half years follow-up, in accordance with some recent publications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17574308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Clinical and biochemical stabilization of Nelson's syndrome with long-term low-dose cabergoline treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16845600", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "We report the results of long-term (6-year) treatment of Nelson's syndrome with the long-acting dopamine agonist, cabergoline, in a 55-year-old woman.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16845600", "endSection": "abstract" }, { "offsetInBeginSection": 1210, "offsetInEndSection": 1322, "text": "This case demonstrates that long-term cabergoline treatment may be efficient in patients with Nelson's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16845600", "endSection": "abstract" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1088, "text": "Therefore, in addition to prolactinomas, targets of dopamine agonist therapy are somatotroph tumors, nonfunctioning pituitary tumors, corticotroph pituitary tumors, Nelson's syndrome, gonadotropinomas, and thyrotropin-secreting pituitary tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16311416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Nelson's syndrome: complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15557761", "endSection": "title" }, { "offsetInBeginSection": 1610, "offsetInEndSection": 1803, "text": "The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson's syndrome in the presence of a pituitary macroadenoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15557761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Complete remission of Nelson's syndrome after 1-year treatment with cabergoline.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10710275", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "In this case report we demonstrated that treatment with the long-acting D2 receptor agonist cabergoline for 1 year induced normalization of plasma ACTH levels and disappearance of the pituitary tumor in a patient with Nelson's syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10710275", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1606, "text": "This case demonstrated that cabergoline treatment is able to induce the remission of Nelson's syndrome and may be a valid therapeutic alternative in this syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10710275", "endSection": "abstract" }, { "offsetInBeginSection": 2235, "offsetInEndSection": 2409, "text": "However, some preliminary data suggest a potential use of cabergoline in combination with ketoconazole, or alone, in selected cases of Cushing's disease or Nelson's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10971110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "We report the results of long-term (6-year) treatment of Nelson's syndrome with the long-acting dopamine agonist, cabergoline, in a 55-year-old woman. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16845600", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 297, "text": "actinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's diseas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702648", "endSection": "abstract" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1223, "text": "In order to investigate on the direct effect played by cabergoline treatment on the remission of Nelson's syndrome, the treatment was withdrawn.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10710275", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 529, "text": "lactinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's disease (CD).OBJECTIVE: To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD.METHODS: Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic cente", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20702648", "endSection": "abstract" } ] }, { "body": "Are mucins glycosylated proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31907968", "http://www.ncbi.nlm.nih.gov/pubmed/31908009", "http://www.ncbi.nlm.nih.gov/pubmed/31904283" ], "ideal_answer": [ "Yes,\nMany members of the mucin family are evolutionarily conserved and are often aberrantly expressed and glycosylated in various benign and malignant pathologies leading to tumor invasion, metastasis, and immune evasion." ], "exact_answer": "yes", "type": "yesno", "id": "604903551cb411341a000162", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Many\u00a0members of the mucin family are evolutionarily conserved and are often aberrantly expressed and glycosylated in various benign and malignant pathologies leading to tumor invasion, metastasis, and immune evasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31908009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Mucin is a glycoprotein that is the primary component of the mucus overlaying the epithelial tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31907968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "Mucin-type O-linked glycosylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31904283", "endSection": "abstract" } ] }, { "body": "Is carpal tunnel syndrome a type of nerve entrapment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3618059", "http://www.ncbi.nlm.nih.gov/pubmed/25526716", "http://www.ncbi.nlm.nih.gov/pubmed/15605660", "http://www.ncbi.nlm.nih.gov/pubmed/19534294", "http://www.ncbi.nlm.nih.gov/pubmed/32174033", "http://www.ncbi.nlm.nih.gov/pubmed/22492102", "http://www.ncbi.nlm.nih.gov/pubmed/32477509", "http://www.ncbi.nlm.nih.gov/pubmed/24740988", "http://www.ncbi.nlm.nih.gov/pubmed/23997744", "http://www.ncbi.nlm.nih.gov/pubmed/19756731", "http://www.ncbi.nlm.nih.gov/pubmed/31634868", "http://www.ncbi.nlm.nih.gov/pubmed/16558255", "http://www.ncbi.nlm.nih.gov/pubmed/28447963", "http://www.ncbi.nlm.nih.gov/pubmed/24422297", "http://www.ncbi.nlm.nih.gov/pubmed/21845587", "http://www.ncbi.nlm.nih.gov/pubmed/29218119", "http://www.ncbi.nlm.nih.gov/pubmed/31632712", "http://www.ncbi.nlm.nih.gov/pubmed/28718333", "http://www.ncbi.nlm.nih.gov/pubmed/31736403", "http://www.ncbi.nlm.nih.gov/pubmed/18050074", "http://www.ncbi.nlm.nih.gov/pubmed/23799199", "http://www.ncbi.nlm.nih.gov/pubmed/28824352", "http://www.ncbi.nlm.nih.gov/pubmed/10918251", "http://www.ncbi.nlm.nih.gov/pubmed/21320832", "http://www.ncbi.nlm.nih.gov/pubmed/32082444", "http://www.ncbi.nlm.nih.gov/pubmed/12475522", "http://www.ncbi.nlm.nih.gov/pubmed/33141768", "http://www.ncbi.nlm.nih.gov/pubmed/28928252", "http://www.ncbi.nlm.nih.gov/pubmed/23113142", "http://www.ncbi.nlm.nih.gov/pubmed/33151661", "http://www.ncbi.nlm.nih.gov/pubmed/6756339", "http://www.ncbi.nlm.nih.gov/pubmed/19280893" ], "ideal_answer": [ "Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy in humans.", "Carpal tunnel syndrome (CTS) is a type of nerve entrapment due to compression of the nerve root extraforaminally between the wrist and the wrist at the carpal tunnel.", "Carpal tunnel syndrome is a neuropathy resulting from compression of the median nerve as it passes through a narrow tunnel in the wrist on its way to the hand.", "Carpal tunnel syndrome (CTS) is the most common focal entrapment mononeuropathy, comprising medium nerve chronic inflammation and fibrosis.", "Carpal tunnel syndrome (CTS) is a focal compressive neuropathy of the central nervous system causing hemorrhage-prone multiple lumen vascular malformation and very severe neurological consequences", "Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes", "Carpal tunnel syndrome (CTS) is a type of nerve entrapment due to compression of the nerve root ganglion as it travels through the wrist at the carpal tunnel." ], "exact_answer": "yes", "type": "yesno", "id": "601d73ee1cb411341a00003f", "snippets": [ { "offsetInBeginSection": 8, "offsetInEndSection": 125, "text": " Carpal tunnel syndrome (CTS) is a common entrapment neuropathy, often requiring carpal tunnel release (CTR) surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33141768", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 126, "text": "Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31736403", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 95, "text": " Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy in humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31634868", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Carpal tunnel syndrome (CTS) is the most common focal entrapment mononeuropathy, comprising medium nerve chronic inflammation and fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32174033", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 161, "text": "Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy which is the result of the compression of the median nerve in the wrist. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32477509", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28447963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "BACKGROUND: Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19534294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND: Carpal tunnel syndrome and ulnar nerve entrapment at the elbow are the most common entrapment neuropathies seen in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21320832", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 386, "text": "Entrapment neuropathies are of various types, but the most common type is carpal tunnel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29218119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Carpal Tunnel Syndrome and Other Entrapment Neuropathies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29218119", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 378, "text": "Unlike Guyon's canal syndrome, carpal tunnel syndrome (CTS) is the most common nerve entrapment of the upper extremity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21845587", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 636, "text": " chronic renal failure tend to develop peripheral nerve entrapment and carpal tunnel syndrome is the best-known peripheral entrapment neuropathy among them. Contrary to ca", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18050074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist. Bifi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28928252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "INTRODUCTION: Carpal tunnel syndrome (CTS) is considered a simple entrapment of the median nerve at the carp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22492102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Compressive neuropathy of the median nerve at the level of the carpal tunnel, known as carpal tunnel syndrome, is the most common entrapment neuropathy, affecting about 0.1-1% of the general population. Magne", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32082444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "BACKGROUND: Carpal tunnel syndrome (CTS) is entrapment of median nerve in carpal tunnel of th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23113142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010). This syndr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28447963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "OBJECTIVE: Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplastici", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23799199", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Carpal tunnel syndrome (CTS), caused by entrapment of the median nerve in the carpal tunnel, impairs hand function including dexterous manipulation. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28824352", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 655, "text": "This review focuses on three of the most common entrapment neuropathies in the upper limbs: carpal tunnel syndrome (median nerve entrapment at the wrist), cubital tunnel syndrome (ulnar nerve entrapment at the elbow), and radial tunnel syndrome (posterior interosseous nerve entrapment).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10918251", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 423, "text": "Electrodiagnostic (EDX) testing is usually an essential part of the evaluation of entrapment neuropathies, and examinations for the most common entrapment neuropathies, carpal tunnel syndrome and ulnar neuropathy at the elbow, constitute a significant part of the daily work in EDX laboratories.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33151661", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 985, "text": "This study reviews the existing, more or less, detailed EDX criteria or practice parameters that are suggested by consensus groups in peer-reviewed journals for the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow, common peroneal (fibular) neuropathy at the fibular head, and tibial neuropathy at the tarsal tunnel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33151661", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 355, "text": "This report demonstrates that the Semmes-Weinstein monofilament test and nerve conduction studies can identify entrapment of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12475522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Entrapment neuropathy of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12475522", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "A case of the entrapment neuropathy of the palmar cutaneous branch of the median nerve, concomitant with carpal tunnel syndrome is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12475522", "endSection": "abstract" }, { "offsetInBeginSection": 476, "offsetInEndSection": 686, "text": "The entrapment syndromes discussed are suprascapular nerve entrapment, carpal tunnel syndrome, cubital tunnel syndrome, meralgia paraesthetica, thoracic outlet syndrome and anterior interosseous nerve syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25526716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Carpal tunnel syndrome is a neuropathy resulting from compression of the median nerve as it passes through a narrow tunnel in the wrist on its way to the hand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16558255", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 587, "text": "More typically, carpal tunnel syndrome is the most common peripheral entrapment neuropathy encountered in industry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16558255", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 248, "text": "Carpal tunnel syndrome is the most frequently encountered peripheral nerve entrapment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19280893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Carpal tunnel syndrome, an entrapment neuropathy of the median nerve, is rarely seen in childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19756731", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 136, "text": "Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19534294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Carpal tunnel syndrome (CTS) is a nerve entrapment disorder, involving the median nerve when it passes the carpal tunnel at the wrist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15605660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The carpal tunnel syndrome is the most frequent entrapment syndrome of peripheral nerves.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3618059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "BACKGROUND: Compression of the median nerve at the wrist, or carpal tunnel syndrome, is the most commonly recognized nerve entrapme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28718333", "endSection": "abstract" }, { "offsetInBeginSection": 1022, "offsetInEndSection": 1096, "text": "Carpal tunnel syndrome is the most common of the median nerve entrapments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6756339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "BACKGROUND: Carpal tunnel syndrome (CTS) is by far the most common entrapment neuropathy (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23997744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Introduction: Carpal tunnel syndrome, entrapment of median nerve at the wrist, is one of the most commonly encountered peripheral neuropathies in the up", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31632712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24740988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28928252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "[Carpal tunnel syndrome and other nerve entrapment syndromes].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24422297", "endSection": "title" } ] }, { "body": "What is the main manifestation of Liebenberg syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23940102", "http://www.ncbi.nlm.nih.gov/pubmed/23395106", "http://www.ncbi.nlm.nih.gov/pubmed/23587911" ], "ideal_answer": [ "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly.", "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly . It is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics .", "People who are affected by Liebenberg Syndrome suffer from three main symptoms: Dysplasia (improper formation) of the bony components of the elbow. Abnormal shape of carpal bones. Brachydactyly, a symptom where the fingers and toes are shorter than normal.", "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition . It is characterized by dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly . We speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds .", "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly" ], "exact_answer": [ "elbow dysplasia" ], "type": "factoid", "id": "5e4565c63f54159529000001", "snippets": [ { "offsetInBeginSection": 385, "offsetInEndSection": 513, "text": "We discuss the genetic abnormality that causes Liebenberg syndrome, the genomic rearrangement at the PITX1 locus on chromosome 5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940102", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 228, "text": "We note that the forearm and hand malformations have similarities to leg and foot anatomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23395106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 997, "text": "We therefore re-define the phenotype of Liebenberg syndrome as a transformation of the upper limbs to reflect lower limb characteristics and speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" } ] }, { "body": "Which IDH inhibitors by Agios Pharmaceuticals have been approved by the FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31660152" ], "ideal_answer": [ "Enasidenib and ivosidenib, the IDH2 and IDH1 inhibitors developed by Agios Pharmaceuticals, have been approved by the Food and Drug Administration" ], "exact_answer": [ [ "Enasidenib" ], [ "Ivosidenib" ] ], "type": "list", "id": "6028fe391cb411341a000104", "snippets": [ { "offsetInBeginSection": 545, "offsetInEndSection": 836, "text": "Hence, enasidenib and ivosidenib, the IDH2 and IDH1 inhibitors developed by Agios Pharmaceuticals, have been approved by the Food and Drug Administration on 1 August 2017 and 20 July 2018 for the treatment of adult relapsed or refractory (R/R) AML with IDH2 and IDH1 mutations, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31660152", "endSection": "abstract" } ] }, { "body": "What is RADICL-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32094342" ], "ideal_answer": [ "Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq) is a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure.", "RADICL-seq is a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. It identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA- chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure.", "RADICL-seq is a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. It is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL -seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA- chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure." ], "type": "summary", "id": "602969061cb411341a000114", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32094342", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1024, "text": "Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32094342", "endSection": "abstract" } ] }, { "body": "Which disease is treated with Anti\u2013Siglec-8 Antibody?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29680938", "http://www.ncbi.nlm.nih.gov/pubmed/31465299", "http://www.ncbi.nlm.nih.gov/pubmed/31401630", "http://www.ncbi.nlm.nih.gov/pubmed/33085861" ], "ideal_answer": [ "Anti-Siglec-8 Antibody was shown to be effective for Eosinophilic Gastritis and Duodenitis. It is also undergoing clinical investigation for treatment of allergic, inflammatory, and proliferative diseases." ], "exact_answer": [ "Eosinophilic Gastritis and Duodenitis" ], "type": "factoid", "id": "601cb4541cb411341a000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085861", "endSection": "title" }, { "offsetInBeginSection": 262, "offsetInEndSection": 465, "text": "AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085861", "endSection": "abstract" }, { "offsetInBeginSection": 2117, "offsetInEndSection": 2241, "text": "ONCLUSIONS: In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085861", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 593, "text": "AK002 is a humanized, non-fucosylated IgG1 anti-Siglec-8 antibody undergoing clinical investigation for treatment of allergic, inflammatory, and proliferative diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31401630", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 874, "text": "Early clinical data with emerging therapies such as dexpramipexole and anti-Siglec-8 antibody show promise, but need to be confirmed in randomized trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29680938", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 466, "text": "(lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 630, "text": "Aberrant accumulation and activation of eosinophils and potentially mast cells (MCs) contribute to the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), including eosinophilic esophagitis (EoE), gastritis (EG), and gastroenteritis (EGE). Current treatment options, such as diet restriction and corticosteroids, have limited efficacy and are often inappropriate for chronic use. One promising new approach is to deplete eosinophils and inhibit MCs with a monoclonal antibody (mAb) against sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8), an inhibitory receptor selectively expressed on MCs and eosinophils", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31465299", "endSection": "abstract" } ] }, { "body": "What is known about mammalian melatonin receptors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12957828", "http://www.ncbi.nlm.nih.gov/pubmed/14521626", "http://www.ncbi.nlm.nih.gov/pubmed/12111545", "http://www.ncbi.nlm.nih.gov/pubmed/30915128" ], "ideal_answer": [ "Melatonin receptors MT1 and MT2 (genes officially named MTNR1A and MTNR1B, respectively) play crucial roles in melatonin-mediated regulation of circadian rhythms, the immune system, and control of reproduction in seasonally breeding animals.\nThe melatonin receptor family is a small group of receptors within the G protein-coupled receptor (GPCR) superfamily. The group comprises of three subtypes which bind melatonin and one member, the melatonin related receptor (MRR), that shares >40% sequence identity with the other melatonin receptors but does not bind melatonin." ], "type": "summary", "id": "60321c531cb411341a000135", "snippets": [ { "offsetInBeginSection": 773, "offsetInEndSection": 956, "text": "activation of melatonin receptors (MT1, MT2, and MT3) highlighting their involvement in modulation of CNS, hypothalamic-hypophyseal-gonadal axis, cardiovascular, and immune functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12957828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "The melatonin receptor family is a small group of receptors within the G protein-coupled receptor (GPCR) superfamily. The group comprises of three subtypes which bind melatonin and one member, the melatonin related receptor (MRR), that shares >40% sequence identity with the other melatonin receptors but does not bind melatonin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14521626", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 510, "text": "Its effects are mediated via high-affinity melatonin receptors, located on cells of the pituitary pars tuberalis (PT) and suprachiasmatic nucleus (SCN), respectively. Two subtypes of mammalian melatonin receptors have been cloned and characterized, the MT1 (Mel(1a)) and the MT2 (Mel(1b)) melatonin receptor subtypes. Both subtypes are members of the seven-transmembrane G protein-coupled receptor family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12111545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Melatonin receptors MT1 and MT2 (genes officially named MTNR1A and MTNR1B, respectively) play crucial roles in melatonin-mediated regulation of circadian rhythms, the immune system, and control of reproduction in seasonally breeding animals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30915128", "endSection": "abstract" } ] }, { "body": "What is holoprosencephaly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25590404", "http://www.ncbi.nlm.nih.gov/pubmed/25218063", "http://www.ncbi.nlm.nih.gov/pubmed/6633857", "http://www.ncbi.nlm.nih.gov/pubmed/26564444", "http://www.ncbi.nlm.nih.gov/pubmed/23112757", "http://www.ncbi.nlm.nih.gov/pubmed/29770996", "http://www.ncbi.nlm.nih.gov/pubmed/21795094", "http://www.ncbi.nlm.nih.gov/pubmed/31528602", "http://www.ncbi.nlm.nih.gov/pubmed/33111505", "http://www.ncbi.nlm.nih.gov/pubmed/26361024", "http://www.ncbi.nlm.nih.gov/pubmed/8862623", "http://www.ncbi.nlm.nih.gov/pubmed/25339593", "http://www.ncbi.nlm.nih.gov/pubmed/27086438", "http://www.ncbi.nlm.nih.gov/pubmed/15021236" ], "ideal_answer": [ "Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis . The most common developmental defect is characterized by inadequate or absent midline division of the forebrain into cerebral hemispheres with concomitant midline facial defects in the majority of cases .", "Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis.", "Holoprosencephaly is a congenital defect of the brain, median structures, and face resulting from incomplete incomplete cleavage of the primitive brain during early embryogenesis.", " Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis." ], "type": "summary", "id": "601ebe451cb411341a00005e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31528602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Holoprosencephaly (HPE) is the most common developmental defect of the forebrain characterized by inadequate or absent midline division of the forebrain into cerebral hemispheres, with concomitant midline facial defects in the majority of cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25339593", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 348, "text": " Holoprosencephaly (HPE) is a severe brain malformation characterized by abnormal cleavage of the prosencephalon in the 5th gestational week. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25590404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND AND PURPOSE: Holoprosencephaly is a rare developmental brain abnormality with a range of severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26564444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND: Holoprosencephaly is the most common malformation of the forebrain (1 in 250 embryos) with severe consequences for fetal and child development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33111505", "endSection": "abstract" }, { "offsetInBeginSection": 15, "offsetInEndSection": 109, "text": "PURPOSE: Holoprosencephaly is a rare developmental brain abnormality with a range of severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26564444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Holoprosencephaly is the most common malformation of the forebrain and typically results in severe neurocognitive impairment with accompanying midline facial anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23112757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Holoprosencephaly is a rare brain abnormality resulting from an incomplete cleavage of the primitive prosencephalon of forebrain during early embryogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21795094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Holoprosencephaly is a brain malformation that develops as a result of a defect in development of prosencephalon during early gestation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27086438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "PURPOSE OF REVIEW: Holoprosencephaly is a disorder of forebrain development characterized by a failure of the brain to separate into two hemispheres during early development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15021236", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 347, "text": "Holoprosencephaly (HPE) is a severe brain malformation characterized by abnormal cleavage of the prosencephalon in the 5th gestational week.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25590404", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Holoprosencephaly is a brain defect resulting from incomplete cleavage of the embryonic forebrain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8862623", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Holoprosencephaly is a spectrum of congenital defects of forebrain development characterized by incomplete separation of the cerebral hemispheres.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29770996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Holoprosencephaly is a brain anomaly of varying severity with associated extracranial, symptomatic abnormalities in only a minority of cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6633857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "PURPOSE OF REVIEW: Holoprosencephaly is a disorder of forebrain development characterized by a failure of the brain to separate into two hemispheres during", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15021236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "BACKGROUND: Holoprosencephaly is a structural anomaly of the brain that consists in a defect of the prosencephalon development that leads to face and neurological defects of variable intensity.AIM: To estimate holoprosencephaly prevalence at birth.PATIENTS AND METHODS: All cases of holoprosencephaly, born alive or stillbirths, registered in the 15 Chilean Hospitals of the Latin American Collaborative Study of Congenital Malformations (ECLAM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26361024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Holoprosencephaly is a clinically and genetically heterogeneous midline brain malformation associated with neurologic manifestations including developmental delay, intellectual disability and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218063", "endSection": "abstract" } ] }, { "body": "What is the effect of notch in the division of neural progenitor cells in Drosophila?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24583034", "http://www.ncbi.nlm.nih.gov/pubmed/18956012", "http://www.ncbi.nlm.nih.gov/pubmed/28573150", "http://www.ncbi.nlm.nih.gov/pubmed/30176986", "http://www.ncbi.nlm.nih.gov/pubmed/19783418", "http://www.ncbi.nlm.nih.gov/pubmed/15081359", "http://www.ncbi.nlm.nih.gov/pubmed/12100893", "http://www.ncbi.nlm.nih.gov/pubmed/19059466", "http://www.ncbi.nlm.nih.gov/pubmed/18000541", "http://www.ncbi.nlm.nih.gov/pubmed/25336612", "http://www.ncbi.nlm.nih.gov/pubmed/27466320", "http://www.ncbi.nlm.nih.gov/pubmed/33229432", "http://www.ncbi.nlm.nih.gov/pubmed/11234018" ], "ideal_answer": [ "The Notch pathway mediates the differentiation of neural progenitor cells in Drosophila. It's an important part of the development of neural stem cells, which are the cells that make up the brain. Notch/HES signaling and MIR-9 signaling are very important for the homeostasis of neural cells. It is thought that notch activation is responsible for the growth of neurons.", "Canonical Notch signaling has diverse functions during nervous system development and is critical for neural progenitor self-renewal, timing of differentiation and specification of various cell fates. In the adult mammalian brain niches for neural stem cells are maintained, which enable a steady-state neurogenesis. This process is tightly regulated by multiple niche factors, including Notch and NF-\u03baB signaling. As a result of Notch activation, neuronal differentiation is inhibited in neighboring cells and they remain neural progenitor cells.", "Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Disruption of Notch signaling causes neuronal progenitor cell self-renewal, a hallmark of systemic lupus erythematosus (SLE), and leads to premature differentiation of them into the erythroid lineage.", "Canonical Notch signaling has diverse functions during nervous system development and is critical for neural progenitor self-renewal, timing of differentiation and specification of various cell fates In the adult mammalian brain niches for neural stem cells are maintained, which enable a steady-state neurogenesis. This process is tightly regulated by multiple niche factors, including Notch and NF-?B signaling. As a result of Notch activation, neuronal differentiation is inhibited in neighboring cells and they remain neural progenitor cells.", "The Notch pathway mediates the differentiation of neural progenitor cells in Drosophila. It's an important part of the development of neural stem cells, which are the cells that make up the brain. Notch/HES signaling and MIR-9 signaling are very important for the homeostasis of neural cells." ], "type": "summary", "id": "5e4bf7876d0a27794100002c", "snippets": [ { "offsetInBeginSection": 82, "offsetInEndSection": 304, "text": "Studies on Drosophila neural progenitors have provided valuable insight into how evolutionarily conserved protein cassettes may be differentially deployed in different developmental contexts to mediate asymmetric divisions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12100893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Asymmetric cell divisions can be mediated by the preferential segregation of cell-fate determinants into one of two sibling daughters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11234018", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 521, "text": "Here we show that the retromer complex directly and specifically regulates Notch receptor retrograde trafficking in Drosophila neuroblast lineages to ensure the unidirectional Notch signaling from neural progenitors to neuroblasts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30176986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "The correct establishment and maintenance of unidirectional Notch signaling are critical for the homeostasis of various stem cell lineages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30176986", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1233, "text": "Our results therefore unveil a safeguard mechanism whereby retromer retrieves potentially harmful Notch receptors in a timely manner to prevent aberrant Notch activation-induced neural progenitor dedifferentiation and brain tumor formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30176986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Notch/Hes signaling and miR-9 engage in complex feedback interactions controlling neural progenitor cell proliferation and differentiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28573150", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Canonical Notch signaling has diverse functions during nervous system development and is critical for neural progenitor self-renewal, timing of differentiation and specification of various cell fates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28573150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "In the adult mammalian brain niches for neural stem cells are maintained, which enable a steady-state neurogenesis. This process is tightly regulated by multiple niche factors, including Notch and NF-\u03baB signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24583034", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 261, "text": "As a result of Notch activation, neuronal differentiation is inhibited in neighboring cells and they remain neural progenitor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19783418", "endSection": "abstract" }, { "offsetInBeginSection": 770, "offsetInEndSection": 875, "text": "We highlight the role of Notch signaling in proliferation and differentiation of neural progenitor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19783418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The Notch pathway mediates expansion of a progenitor pool and neuronal differentiation in adult neural progenitor cells after stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19059466", "endSection": "title" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1234, "text": "Inhibition of the Notch pathway with a gamma secretase inhibitor further substantially increased neurons, but did not alter astrocyte population in ischemic neural progenitor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19059466", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1259, "text": "The activation of NOTCH signalling by DELTA-1 in the adjacent progenitors inhibits neurogenesis and is required to maintain proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18000541", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 514, "text": "We show that conditional expression of a constitutively active form of Notch1 in early neural progenitor cells, but not postmitotic neurons, selectively induces extensive apoptosis, resulting in a markedly reduced progenitor population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15081359", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 936, "text": "This dynamic mode of gene expression would require a revision of the traditional view of how Notch-mediated lateral inhibition operates in the developing mammalian nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18956012", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 1027, "text": "Our data therefore suggest that Numb controls the balance between Notch receptor recycling and receptor targeting to late endosomes to regulate signaling output after asymmetric cell division in Drosophila neural progenitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27466320", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 409, "text": "Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that, in every asymmetric cell division, progenitors send a Delta-Notch signal to their sibling stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33229432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Notch activity in neural progenitors coordinates cytokinesis and asymmetric differentiation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25336612", "endSection": "title" } ] }, { "body": "In what clinical trials has SAR425899 been tested?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30091218" ], "ideal_answer": [ "Subcutaneous administrations of SAR425899 were tested in two randomized, placebo-controlled, double-blind clinical trials. In the first trial, healthy overweight volunteers (body mass index [BMI] 25-30\u2009kg/m2 ; n\u2009=\u200932) received single-ascending doses (0.01-0.1 mg) of SAR425899 or placebo. In the second, a multiple-ascending-dose trial (NCT02411825), healthy normal- to overweight volunteers (BMI 20-30\u2009kg/m2 ; n\u2009=\u200940) and overweight/obese patients with T2D (BMI 28-42\u2009kg/m2 ; n\u2009=\u200936) received daily doses of SAR425899 or placebo over 21 or 28\u2009days, respectively." ], "type": "summary", "id": "602c21501cb411341a000121", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30091218", "endSection": "title" }, { "offsetInBeginSection": 302, "offsetInEndSection": 865, "text": "Subcutaneous administrations of SAR425899 were tested in two randomized, placebo-controlled, double-blind clinical trials. In the first trial, healthy overweight volunteers (body mass index [BMI] 25-30\u2009kg/m2 ; n\u2009=\u200932) received single-ascending doses (0.01-0.1 mg) of SAR425899 or placebo. In the second, a multiple-ascending-dose trial (NCT02411825), healthy normal- to overweight volunteers (BMI 20-30\u2009kg/m2 ; n\u2009=\u200940) and overweight/obese patients with T2D (BMI 28-42\u2009kg/m2 ; n\u2009=\u200936) received daily doses of SAR425899 or placebo over 21 or 28\u2009days, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30091218", "endSection": "abstract" } ] }, { "body": "Is there a link between rare variants in PPARG and type 1 diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25157153" ], "ideal_answer": [ "No. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes.", "No. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes" ], "exact_answer": "no", "type": "yesno", "id": "602905e81cb411341a000108", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25157153", "endSection": "title" }, { "offsetInBeginSection": 585, "offsetInEndSection": 1521, "text": "By sequencing PPARG in 19,752 T2D cases and controls drawn from multiple studies and ethnic groups, we identified 49 previously unidentified, nonsynonymous PPARG variants (MAF < 0.5%). Considered in aggregate (with or without computational prediction of functional consequence), these rare variants showed no association with T2D (OR = 1.35; P = 0.17). The function of the 49 variants was experimentally tested in a novel high-throughput human adipocyte differentiation assay, and nine were found to have reduced activity in the assay. Carrying any of these nine LOF variants was associated with a substantial increase in risk of T2D (OR = 7.22; P = 0.005). The combination of large-scale DNA sequencing and functional testing in the laboratory reveals that approximately 1 in 1,000 individuals carries a variant in PPARG that reduces function in a human adipocyte differentiation assay and is associated with a substantial risk of T2D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25157153", "endSection": "abstract" } ] }, { "body": "What is the mechanisms of action of pexidartinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31229240", "http://www.ncbi.nlm.nih.gov/pubmed/31420495", "http://www.ncbi.nlm.nih.gov/pubmed/30926949", "http://www.ncbi.nlm.nih.gov/pubmed/32440095", "http://www.ncbi.nlm.nih.gov/pubmed/31862477", "http://www.ncbi.nlm.nih.gov/pubmed/30825104", "http://www.ncbi.nlm.nih.gov/pubmed/32535390", "http://www.ncbi.nlm.nih.gov/pubmed/32251854", "http://www.ncbi.nlm.nih.gov/pubmed/31602563", "http://www.ncbi.nlm.nih.gov/pubmed/31258629", "http://www.ncbi.nlm.nih.gov/pubmed/31213500", "http://www.ncbi.nlm.nih.gov/pubmed/33143617", "http://www.ncbi.nlm.nih.gov/pubmed/31240240", "http://www.ncbi.nlm.nih.gov/pubmed/31848580", "http://www.ncbi.nlm.nih.gov/pubmed/32306101", "http://www.ncbi.nlm.nih.gov/pubmed/32943455" ], "ideal_answer": [ "Pexidartinib is small-molecule tyrosine kinase inhibitor that has strong selectivity against colony-stimulating factor 1 receptor." ], "type": "summary", "id": "6025f7dc1cb411341a0000bd", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30825104", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30825104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The CSF1 receptor inhibitor pexidartinib (PLX3397) reduces tissue macrophage levels without affecting glucose homeostasis in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30926949", "endSection": "title" }, { "offsetInBeginSection": 207, "offsetInEndSection": 454, "text": "Colony-stimulating factor 1 (CSF1) controls macrophage differentiation, and here we sought to determine the effect of a CSF1 receptor inhibitor, PLX3397, on adipose tissue macrophage levels and understand the impact on glucose homeostasis in mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30926949", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 461, "text": "To address the role of these cells in disease pathogenesis, we depleted microglia from R6/2 mice, a rapidly progressing model of Huntington's disease marked by behavioural impairment, mutant huntingtin (mHTT) accumulation, and early death, through colony-stimulating factor 1 receptor inhibition (CSF1Ri) with pexidartinib (PLX3397) for the duration of disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31848580", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 818, "text": "Pexidartinib is a CSF1R antagonist that is prescribed for the treatment of tenosynovial giant cell tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31862477", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 455, "text": "Methods: Female MMTV-PyMT mice were treated with pexidartinib, a colony-stimulating factor 1 receptor (CSF1R) inhibitor, to reduce TAM density. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420495", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 1073, "text": "ODS: This was an investigator-initiated, phase I, dose escalation study of the MEK inhibitor binimetinib combined with pexidartinib, a potent inhibitor of CSF1R, KIT, and FLT3, in patients with advanced or metastatic GIST who progressed on imatinib. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31213500", "endSection": "abstract" }, { "offsetInBeginSection": 1035, "offsetInEndSection": 1196, "text": "We evaluated the recently FDA-approved CSF1R inhibitor Pexidartinib (PLX3397) in OSA cell lines in vitro and in vivo in cell line and patient-derived xenografts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32251854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Pexidartinib (TURALIO\u2122) is an orally administered small molecule tyrosine kinase inhibitor with selective activity against the colony-stimulating factor 1 (CSF1) receptor, KIT proto-oncogene receptor tyrosine kinase (KIT) and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation (FLT3-ITD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31602563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "PURPOSE: Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306101", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 1203, "text": "amics of pexidartinib. Special attention is given to various reported clinical trials of pexidartinib.METHODS: A comprehensive literature search was conducted in the relevant databases to identify studies published in this field during recent years Conclusion: Pexidartinib acts by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway which leads to inhibition of the cell lines proliferation and promotes the autophosphorylation process ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33143617", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 315, "text": " tumors. Pexidartinib, an oral inhibitor of tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), KIT, and FLT3, is FDA approved in adults with tenosynovial giant ce", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "PURPOSE: Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Pexidartinib, a Novel Small Molecule CSF-1R Inhibitor in Use for Tenosynovial Giant Cell Tumor: A Systematic Review of Pre-Clinical and Clinical Development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32440095", "endSection": "title" }, { "offsetInBeginSection": 428, "offsetInEndSection": 740, "text": "MD simulation indicated (-)-kusunokinin and pexidartinib (P31, a specific CSF1R binding compound) shared some extents of functional similarity in which (-)-kusunokinin bound CSF1R at the juxtamembrane (JM) region with aromatic amino acids similar to pexidartinib using \u03c0-\u03c0 interaction, as well as hydrogen bond. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32535390", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 398, "text": "Surgery is standard with no approved systemic therapy. We aimed to evaluate pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT to provide them with a viable systemic treatment option, especially in cases that are not amenable to surgical resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31229240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31258629", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Purpose: To evaluate the safety, recommended phase\u2009II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor\u20091 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31258629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Pexidartinib (PLX3397) is a small molecule tyrosine kinase and colony-stimulating factor-1 inhibitor with FDA breakthrough therapy designation for tenosynovial giant-cell tumor, and currently under study in several other tumor types, including breast cancer, non-Hodgkin's lymphoma, and glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31240240", "endSection": "abstract" } ] }, { "body": "List pore forming toxins.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30914205", "http://www.ncbi.nlm.nih.gov/pubmed/32041354", "http://www.ncbi.nlm.nih.gov/pubmed/31903844", "http://www.ncbi.nlm.nih.gov/pubmed/31584206", "http://www.ncbi.nlm.nih.gov/pubmed/31852826", "http://www.ncbi.nlm.nih.gov/pubmed/32492702", "http://www.ncbi.nlm.nih.gov/pubmed/31936048" ], "ideal_answer": [ "cytolysin A\n\u03b1-hemolysin\nStreptolysin O\npneumolysin\nlisteriolysin\nleukocidin\nGlabralysin" ], "exact_answer": [ [ "cytolysin A" ], [ "\u03b1-hemolysin" ], [ "Streptolysin O" ], [ "pneumolysin" ], [ "leukocidin" ], [ "Glabralysin" ], [ "listeriolysin" ] ], "type": "list", "id": "60321aad1cb411341a000134", "snippets": [ { "offsetInBeginSection": 1133, "offsetInEndSection": 1223, "text": "Application of this algorithm to prototypical \u03b1-PFT (cytolysin A) and \u03b2-PFT (\u03b1-hemolysin) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31903844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Staphylococcal bi-component pore-forming toxins, also known as leukocidins,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32041354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Streptolysin O (SLO) is a bacterial pore-forming toxin that is employed to permeabilize cell membranes in some biological experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31584206", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 245, "text": " S. pneumoniae pneumolysin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492702", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 547, "text": "streptolysin O (SLO)-type and listeriolysin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30914205", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 360, "text": "ere we report the structures of a staphylococcal pore-forming cytotoxin, leukocidin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31852826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Glabralysins, Potential New \u03b2-Pore-Forming Toxin Family Members from the Schistosomiasis Vector Snail Biomphalaria glabrata", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31936048", "endSection": "title" } ] }, { "body": "What syndrome is associated with mutations in lysine methyltransferase 2D KMT2D?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28475860", "http://www.ncbi.nlm.nih.gov/pubmed/28007623", "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "http://www.ncbi.nlm.nih.gov/pubmed/31813957", "http://www.ncbi.nlm.nih.gov/pubmed/24838796", "http://www.ncbi.nlm.nih.gov/pubmed/29914387", "http://www.ncbi.nlm.nih.gov/pubmed/30980591", "http://www.ncbi.nlm.nih.gov/pubmed/29725259", "http://www.ncbi.nlm.nih.gov/pubmed/31282990", "http://www.ncbi.nlm.nih.gov/pubmed/31465303", "http://www.ncbi.nlm.nih.gov/pubmed/24705355", "http://www.ncbi.nlm.nih.gov/pubmed/30891914", "http://www.ncbi.nlm.nih.gov/pubmed/31816409", "http://www.ncbi.nlm.nih.gov/pubmed/32803813", "http://www.ncbi.nlm.nih.gov/pubmed/26194542", "http://www.ncbi.nlm.nih.gov/pubmed/27573763", "http://www.ncbi.nlm.nih.gov/pubmed/26932671", "http://www.ncbi.nlm.nih.gov/pubmed/32083401", "http://www.ncbi.nlm.nih.gov/pubmed/24240169" ], "ideal_answer": [ "Mutations in lysine methyltransferase 2D (KMT2D) gene, which encodes the catalytic core of a multisubunit chromatin remodeling enzyme, are responsible for the neurodegenerative disorder Kabuki syndrome.", "Mutations in lysine methyltransferase 2D (KMT2D) cause Kabuko syndrome.", "Kabuki syndrome (KS) is commonly caused by mutations in the histone-modifying enzyme lysine methyltransferase 2D (KMT2D).", "Mutations in the lysine methyltransferase 2D (KMT2D) gene, which encodes the alpha-subunit of the kappaB gene, are associated with the autosomal dominant hemophagocytic syndrome type 4 or Ferroportin syndrome.", "Kabuki syndrome is a rare autosomal dominant disorder caused by mutations in the lysine methyltransferase 2D (KMT2D) gene." ], "exact_answer": [ "Kabuki syndrome" ], "type": "factoid", "id": "601ebbeb1cb411341a00005b", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 134, "text": "Kabuki syndrome (KS) is commonly caused by mutations in the histone-modifying enzyme lysine methyltransferase 2D (KMT2D). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31816409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Identification of KMT2D and KDM6A variants by targeted sequencing from patients with Kabuki syndrome and other congenital disorders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Kabuki syndrome (KS) is a rare congenital disorder characterized by distinctive facies, postnatal growth deficiency, cardiac defects and skeletal anomalies. Studies have determined that pathogenic variants of the lysine-specific methyltransferase 2D (KMT2D) and lysine-specific demethylase 6A (KDM6A) genes are the major causes of KS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32083401", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 648, "text": "We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32083401", "endSection": "abstract" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1307, "text": "These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32083401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Kabuki syndrome is characterized by a variable degree of intellectual disability, characteristic facial features, and complications in various organs. Many variants have been identified in two causative genes, that is, lysine methyltransferase 2D (KMT2D) and lysine demethylase 6A (KDM6A)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32803813", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 408, "text": "Heterozygous germline mutations in the KMT2D gene are known to cause Kabuki syndrome (OMIM 147920), a developmental multisystem disorder. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31282990", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 441, "text": "Lysine-specific methyltransferase 2D (KMT2D) encodes a histone methyltransferase that promotes transcriptional activation and is frequently mutated in cancers and in the majority (>70%) of patients diagnosed with the congenital, multisystem intellectual disability disorder Kabuki syndrome 1 (KS1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31465303", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 347, "text": "Kabuki syndrome is caused by mutations or deletions of lysine (K)-specific methyltransferase 2D (KMT2D) and lysine-specific methylase 6A (KDM6A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24838796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "BACKGROUND: Kabuki syndrome (KS) is commonly caused by mutations in the histone-modifying enzyme lysine methyltransferase 2D (KMT2D).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31816409", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 536, "text": "JECTIVE: We sought to characterize the humoral immune defects found in patients with KS with lysine methyltransferase 2D (KMT2D) mutations.ME", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194542", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 763, "text": "LTS: We report frequent mutations in the lysine methyltransferase 2D gene (KMT2D) (also known as MLL2), a key regulator of transcriptional enhancer function. KMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007623", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1108, "text": "ound that KMT2D mutation in human SCLC cell lines was associated with reduced lysine methyltransferase 2D protein levels and reduced monomethylation of histone H3 lysine 4, a mark associated with transcriptional enhancers. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28007623", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 361, "text": "Two such disorders, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-binding protein\u00a07 (CHD7LOF) and lysine (K) methyltransferase 2D (KMT2DLOF), respectively. Although these two syndromes are clinically", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28475860", "endSection": "abstract" }, { "offsetInBeginSection": 1676, "offsetInEndSection": 1885, "text": "ONS: In patients with KS, autosomal dominant KMT2D mutations are associated with dysregulation of terminal B-cell differentiation, leading to humoral immune deficiency and, in some cases, autoimmunity. All pat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194542", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 557, "text": "MT2D has emerged as one of the most frequently mutated genes in a variety of cancers and in other human diseases, including lymphoma, medulloblastoma, gastric cancer, and Kabuki syndrome. Mutations in KMT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240169", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 722, "text": " KS was confirmed by genetic testing, which revealed a nonsense mutation in exon\u00a016 of KMT2D (c.4485C>A, Tyr1495Ter). To the best of our", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32083401", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 789, "text": "We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32083401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "KMT2D, which encodes a histone H3K4 methyltransferase, has been implicated in human congenital heart disease in the context of Kabuki syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26932671", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 407, "text": "Heterozygous germline mutations in the KMT2D gene are known to cause Kabuki syndrome (OMIM 147920), a developmental multisystem disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31282990", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 420, "text": "Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29725259", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 536, "text": "e sought to characterize the humoral immune defects found in patients with KS with lysine methyltransferase 2D (KMT2D) mutations.ME", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194542", "endSection": "abstract" }, { "offsetInBeginSection": 1685, "offsetInEndSection": 1881, "text": "atients with KS, autosomal dominant KMT2D mutations are associated with dysregulation of terminal B-cell differentiation, leading to humoral immune deficiency and, in some cases, autoimmunity. All", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26194542", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 438, "text": "Mutations in the KMT2D gene, which encodes a H3K4 histone methyltransferase, are the major cause of Kabuki syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705355", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 527, "text": "The major cause of Kabuki syndrome are mutations in KMT2D, a gene encoding a histone H3 lysine 4 (H3K4) methyltransferase belonging to the group of chromatin modifiers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31813957", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 421, "text": "Mutations with a loss-of-function in the KMT2D gene on chromosome 12 in humans are responsible for Kabuki syndrome (KS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30891914", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 409, "text": "rt defects. Mutations in the histone H3K4 methyltransferase KMT2D have been identified as the main cause of Kabuki syndrome, however, the role of KMT2D in heart development remains to be characterized.RESULTS: Here we analyze the function of Kmt2d at different stages of Xenop", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30980591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The histone methyltransferase KMT2D, mutated in Kabuki syndrome patients, is required for neural crest cell formation and migration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31813957", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "A novel KMT2D mutation resulting in Kabuki syndrome: A case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27573763", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 540, "text": "Recently, KMT2D has emerged as one of the most frequently mutated genes in a variety of cancers and in other human diseases, including lymphoma, medulloblastoma, gastric cancer, and Kabuki syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24240169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A de novo KMT2D mutation in a girl with Kabuki syndrome associated with endocrine symptoms: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29914387", "endSection": "title" } ] }, { "body": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11515490", "http://www.ncbi.nlm.nih.gov/pubmed/23633205", "http://www.ncbi.nlm.nih.gov/pubmed/10458450", "http://www.ncbi.nlm.nih.gov/pubmed/20850730", "http://www.ncbi.nlm.nih.gov/pubmed/27693263", "http://www.ncbi.nlm.nih.gov/pubmed/8110760", "http://www.ncbi.nlm.nih.gov/pubmed/10564874", "http://www.ncbi.nlm.nih.gov/pubmed/21147889", "http://www.ncbi.nlm.nih.gov/pubmed/24383016", "http://www.ncbi.nlm.nih.gov/pubmed/3489839", "http://www.ncbi.nlm.nih.gov/pubmed/8001864", "http://www.ncbi.nlm.nih.gov/pubmed/1944596", "http://www.ncbi.nlm.nih.gov/pubmed/17663907", "http://www.ncbi.nlm.nih.gov/pubmed/20511729", "http://www.ncbi.nlm.nih.gov/pubmed/8302780", "http://www.ncbi.nlm.nih.gov/pubmed/20132346", "http://www.ncbi.nlm.nih.gov/pubmed/8768837" ], "ideal_answer": [ "Yes, steroid 5A-reductase deficiency can lead to hermaphroditism.", "5\u03b1 steroid reductase deficiency (5\u03b1SRD) is an autosomal recessive enzymatic deficiency and mutations in the 5\u03b1 steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis. The diagnosis of steroid-5-alpha-reductase deficiency is rarely considered by the paediatrician.", "Yes, steroid 5A-reductase deficiency is a rare autosomal recessive disorder.", "Yes, steroid 5A-Reductase deficiency is associated with hermaphroditism.", "5\u03b1 steroid reductase deficiency (5\u03b1SRD) is an autosomal recessive enzymatic deficiency and mutations in the 5\u03b1 steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis.", "Male pseudo hermaphroditism caused by steroid 5 alpha reductase deficiency is a rare autosomal recessive disorder. This enzyme catalyses the conversion of testosterone to dihydrotestosterone (DHT) in genital tissue.", "Yes, steroid 5A-reductase deficiency is associated with hermaphroditism." ], "exact_answer": "yes", "type": "yesno", "id": "5fd78702a43ad31278000005", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 253, "text": "5\u03b1 steroid reductase deficiency (5\u03b1SRD) is an autosomal recessive enzymatic deficiency and mutations in the 5\u03b1 steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20511729", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 510, "text": "The diagnosis of steroid-5-alpha-reductase deficiency is rarely considered by the paediatrician. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20132346", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 213, "text": "n 46,XY disorders of sex development, 5\u03b1-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21147889", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 345, "text": "Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5\u03b1-reductase deficiency is essential", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21147889", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1384, "text": "Our data clearly demonstrate that 5\u03b1-reductase deficiency should be considered in XY adolescents with primary amenorrhea and no breast development associated with virilization at puberty and high plasma T. Positive parental consanguinity should reinforce the diagnostic orientation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20850730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Molecular diagnosis of 5\u03b1-reductase deficiency in 4 elite young female athletes through hormonal screening for hyperandrogenism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633205", "endSection": "title" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1550, "text": "The hormonal analysis evidenced plasma T within the male range, the karyotype was 46, XY, and molecular analysis of the 5\u03b1-reductase type 2 (srd5A2) gene identified a homozygotic mutation in 2 cases, a heterozygotic compound in 1 case, and a deletion in 1 case.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633205", "endSection": "abstract" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1754, "text": "5\u03b1-Reductase deficiency should be investigated in elite young female athletes with primary amenorrhea and high male T levels detected during antidoping programs to identify undiagnosed XY DSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23633205", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 389, "text": "Few studies exist on the psychosexual outcome of homogeneous groups of individuals with 5\u03b1-reductase deficiency type 2 (5\u03b1-RD-2) and the relation between gender changes and parental hostile and benevolent sexism, which are two components of ambivalent sexism that assume a stereotypical approach toward women in an overtly negative way or a chivalrous, seemingly positive way", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27693263", "endSection": "abstract" }, { "offsetInBeginSection": 1849, "offsetInEndSection": 2039, "text": "The high prevalence of gender change and gender dysphoria reported in the literature was confirmed in this relatively large and homogeneous sample of Iranians with 5-\u03b1-RD-2 raised as female.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27693263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Male pseudo hermaphroditism caused by steroid 5 alpha reductase deficiency is a rare autosomal recessive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11515490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "[Male pseudo-hermaphroditism due to partial 5 alpha-reductase deficiency, a case report].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11515490", "endSection": "title" }, { "offsetInBeginSection": 249, "offsetInEndSection": 357, "text": "We report two cases of male pseudohermaphroditism, a true hermaphroditism and a 5-alfa-reductase deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17663907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Contrary to what is observed in true hermaphroditism and in male pseudo-hermaphroditism, there is no erroneous transmission of the genetic gonadal differentiation programme in female pseudohermaphroditism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8302780", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 1039, "text": "To our knowledge neither the A49T nor the L113V mutation has been previously reported in association with 5alpha-reductase type 2 deficiency and to date they have only been identified in cases of isolated hypospadias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10458450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The deficiency of steroid 5 alpha-reductase leads to the disturbances in sex differentiation that cause symptoms of male pseudohermaphroditism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8001864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Male pseudohermaphroditism caused by steroid 5alpha-reductase deficiency is an autosomal recessive disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10564874", "endSection": "abstract" }, { "offsetInBeginSection": 1705, "offsetInEndSection": 1930, "text": "This study reveals that 5 alpha-reductase deficiency occurs with a frequency of 13 per cent as a cause of male pseudohermaphroditism in the Dominican Republic with approximately the same frequency as XO/XY gonadal dysgenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3489839", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1944596", "endSection": "title" }, { "offsetInBeginSection": 812, "offsetInEndSection": 1080, "text": "In 5 of 33 male pseudohermaphrodites with a normal testosterone response to human chorionic gonadotropin 5 alpha-reductase deficiency was suspected by elevated plasma testosterone/dihydrotestosterone ratios before and/or after human chorionic gonadotropin stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3489839", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1114, "text": "A deletion in this gene is present in two related individuals with male pseudohermaphroditism caused by 5 alpha-reductase deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1944596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Steroid 5-alpha-reductase 2 deficiency is a rare disorder leading to male pseudohermaphroditism, a condition characterized by incomplete differentiation of male genitalia in 46,XY patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24383016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The present report describes a cluster of eight patients with male pseudohermaphroditism from a large pedigree with steroid 5 alpha-reductase 2 deficiency (5 alpha RD), who reside in Southern Lebanon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8768837", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 640, "text": "Inherited deficiencies of 5 alpha-reductase type 2 result in a form of male pseudohermaphroditism in which the external genitalia fail to develop normally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8110760", "endSection": "abstract" } ] }, { "body": "Has ubrogepant entered clinical phase III trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32011192", "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "http://www.ncbi.nlm.nih.gov/pubmed/32648856" ], "ideal_answer": [ "Yes, ubrogepant has entered phase III trials." ], "exact_answer": "yes", "type": "yesno", "id": "6026db1f1cb411341a0000cf", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 968, "text": "A population pharmacokinetic model describing the effect of formulations was included in the E-R simulation framework to assess potential dose implications of a formulation switch from phase II to phase III. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "endSection": "abstract" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1220, "text": "The understanding of E-R helped support the dose selection for the phase III clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 509, "text": "The CGRP receptor antagonist ubrogepant, also known as MK-1602, has been recently evaluated in phase III clinical trials for clinical efficacy and long-term safety as an abortive migraine treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32011192", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 703, "text": "Two pivotal phase III clinical trials (ACHIEVE I and ACHIEVE II) demonstrated effectiveness and safety of ubrogepant in acute migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648856", "endSection": "abstract" } ] }, { "body": "How many nucleotides long is the HOTAIR CNE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32268280" ], "ideal_answer": [ "The HOTAIR CNE is a 32-nucleotide long conserved noncoding element", "HOTAIR was proposed to regulate either HoxD cluster genes in trans or HoxC cluster genes in cis, a mechanism that remains unclear. A 32-nucleotide conserved noncoding element (CNE) was identified as HOTAIR ancient sequence that likely originated at the root of vertebrate.", "The HOTAIR element is a 32-nucleotide conserved noncoding element" ], "exact_answer": [ "32" ], "type": "factoid", "id": "602967de1cb411341a000113", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 807, "text": "HOTAIR was proposed to regulate either HoxD cluster genes in trans or HoxC cluster genes in cis, a mechanism that remains unclear. We have identified a 32-nucleotide conserved noncoding element (CNE) as HOTAIR ancient sequence that likely originated at the root of vertebrate. The second round of whole-genome duplication resulted in one copy of the CNE within HOTAIR and another copy embedded in noncoding transcript of HOXD11. Paralogous CNEs underwent compensatory mutations, exhibit sequence complementarity with respect to transcripts directionality, and have high affinity in\u00a0vitro. The HOTAIR CNE resembled a poised enhancer in stem cells and an active enhancer in HOTAIR-expressing cells. HOTAIR expression is positively correlated with HOXC11 in cis and negatively correlated with HOXD11 in trans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32268280", "endSection": "abstract" } ] }, { "body": "What symptoms are included in the narcolepsy pentad?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32941089", "http://www.ncbi.nlm.nih.gov/pubmed/30595352", "http://www.ncbi.nlm.nih.gov/pubmed/28726523", "http://www.ncbi.nlm.nih.gov/pubmed/28162143", "http://www.ncbi.nlm.nih.gov/pubmed/31931470" ], "ideal_answer": [ "Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep." ], "exact_answer": [ [ "excessive daytime sleepiness" ], [ "cataplexy" ], [ "sleep paralysis" ], [ "hypnagogic/hypnopompic hallucinations" ], [ "disturbed nocturnal sleep" ] ], "type": "list", "id": "60274a2a1cb411341a0000e2", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Disrupted nighttime sleep is one of the pentad of symptoms defining Narcolepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31931470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32941089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "BACKGROUND: Narcolepsy is a disabling sleep-wake disorder characterized by the pentad symptoms of excessive daytime sleepiness, sleep paralysis, sleep fragmentation, sleep-related hallucinations, and cataplexy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28726523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "STUDY OBJECTIVES: Narcolepsy, a chronic disorder of the central nervous system, is clinically characterized by a symptom pentad that includes excessive daytime sleepiness, cataplexy, sleep paralysis, hypnopompic/hypnagogic hallucinations, and disrupted nighttime sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28162143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "BACKGROUND: Narcolepsy is a disabling sleep-wake disorder characterized by the pentad symptoms of excessive daytime sleepiness, sleep paralysis, sleep fragmentation, sleep-related hallucinations, and cataplexy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28726523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32941089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "STUDY OBJECTIVES: Narcolepsy, a chronic disorder of the central nervous system, is clinically characterized by a symptom pentad that includes excessive daytime sleepiness, cataplexy, sleep paralysis, hypnopompic/hypnagogic hallucinations, and disrupted nig", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28162143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed noctur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28726523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "BACKGROUND: Narcolepsy is a disabling sleep-wake disorder characterized by the pentad symptoms of excessive daytime sleepiness, sleep paralysis, sleep fragmentation, sleep-related hallucinations, an", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30595352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed no", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32941089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed no", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28726523", "endSection": "abstract" } ] }, { "body": "What is the function of osteolectin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32003015", "http://www.ncbi.nlm.nih.gov/pubmed/30632962", "http://www.ncbi.nlm.nih.gov/pubmed/33053358" ], "ideal_answer": [ "C-type lectin domain family 11 member A (Clec11a), also known as stem cell growth factor (SCGF), C-type lectin superfamily member 3 (CLECSF3), or osteolectin was initially identified as a growth factor for hematopoietic progenitor cells." ], "exact_answer": [ "osteogenic growth factor" ], "type": "factoid", "id": "604911661cb411341a000169", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "C-type lectin domain family 11 member A (Clec11a), also known as stem cell growth factor (SCGF), C-type lectin superfamily member 3 (CLECSF3), or osteolectin was initially identified as a growth factor for hematopoietic progenitor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32003015", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 412, "text": "bone growth factor Osteolectin,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33053358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "We previously discovered a new osteogenic growth factor that is required to maintain adult skeletal bone mass, Osteolectin/Clec11a.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30632962", "endSection": "abstract" } ] }, { "body": "What is ECMO?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32144062", "http://www.ncbi.nlm.nih.gov/pubmed/24809246", "http://www.ncbi.nlm.nih.gov/pubmed/28413074", "http://www.ncbi.nlm.nih.gov/pubmed/30386759", "http://www.ncbi.nlm.nih.gov/pubmed/29768983", "http://www.ncbi.nlm.nih.gov/pubmed/23817232", "http://www.ncbi.nlm.nih.gov/pubmed/22914430", "http://www.ncbi.nlm.nih.gov/pubmed/28533721", "http://www.ncbi.nlm.nih.gov/pubmed/25608845", "http://www.ncbi.nlm.nih.gov/pubmed/25176974", "http://www.ncbi.nlm.nih.gov/pubmed/25711946", "http://www.ncbi.nlm.nih.gov/pubmed/24651227", "http://www.ncbi.nlm.nih.gov/pubmed/28948652", "http://www.ncbi.nlm.nih.gov/pubmed/29050526", "http://www.ncbi.nlm.nih.gov/pubmed/895593", "http://www.ncbi.nlm.nih.gov/pubmed/32092196", "http://www.ncbi.nlm.nih.gov/pubmed/19088593", "http://www.ncbi.nlm.nih.gov/pubmed/27113690", "http://www.ncbi.nlm.nih.gov/pubmed/29808279", "http://www.ncbi.nlm.nih.gov/pubmed/26837253", "http://www.ncbi.nlm.nih.gov/pubmed/23594433", "http://www.ncbi.nlm.nih.gov/pubmed/32094031", "http://www.ncbi.nlm.nih.gov/pubmed/23406535", "http://www.ncbi.nlm.nih.gov/pubmed/25789816", "http://www.ncbi.nlm.nih.gov/pubmed/19806801" ], "ideal_answer": [ "Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF)", "The method of extracorporeal membrane oxygenation (VA-ECMO) has developed from being used as a 'rescue therapy' to become an accepted treatment option for patients with acute lung failure.", "Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF) and is used to treat severe symptoms of Covid-19 as well as other cases of severe respiratory and/or circulatory failure over periods of several days to several weeks", "Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF)." ], "exact_answer": [ "Extracorporeal membrane oxygenation" ], "type": "factoid", "id": "601d74391cb411341a000041", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Over the last decade, the use of extracorporeal membrane oxygenation (ECMO) has increased significantly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32144062", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 238, "text": "xtracorporeal membrane oxygenation (ECMO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32094031", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 127, "text": " Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29050526", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 164, "text": " Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29768983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "INTRODUCTION: Mortality of patients on extracorporeal membrane oxygenation (ECMO) remains high.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23594433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a form of long-term cardiopulmonary bypass used to treat infants, children, and adults with respiratory and/or cardiac failure despite maximal medical therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19088593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "PURPOSE: Optimal timing of congenital diaphragmatic hernia (CDH) repair in patients requiring extracorporeal membrane oxygenation (ECMO) remains controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29808279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Extracorporeal membrane oxygenation (ECMO) is a support modality used within the pediatric cardiac ICU population as a bridge to recovery or decision in the setting of acute myocardial decompensation, support for combined cardiopulmonary failure or in the setting of refractory cardiopulmonary arrest. Pati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30386759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a widely used technique for treating postcardiotomy cardiogenic shock (PCS); however, no study has compared the long-term outcomes of patients who receive ECMO support for PCS with those of the general population post cardiac su", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28413074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Extracorporeal membrane oxygenation (ECMO) is a kind of technique that uses extracorporeal circulation system to draw patients' blood into the circuit, and then oxygenate the blood when it passes along the membrane, followed by returning the blood into patients. At pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26837253", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 697, "text": "FINDINGS: Major technological improvements in extracorporeal membrane oxygenation (ECMO) machines and the positive results of the conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) trial have reignited interest in VV-ECMO in patients with severe acute respiratory distress syndrome (ARDS) and persistent hypoxemia or hypercarbia on conventional mechanical ventilation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22914430", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 550, "text": "BACKGROUND: The use of extra-corporeal membrane oxygenation (ECMO) for the adult patient has increased slowly since the first reported successful treatment in 1972 (Hill et al., 1972) and is seen increasingly as a successful therapy when conventional medical treatment has failed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24809246", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 918, "text": "METHODS: A literature search was conducted using the PubMed and EMBASE databases with the following keywords: \"extracorporeal membrane oxygenation OR extracorporeal membrane oxygenations OR ECMO\" and \"PK OR pharmacokinetics OR pharmacokinetic*\" and \"anti infective* OR antibiotic* OR antiviral* OR antituberculosis OR antifungal*.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28948652", "endSection": "abstract" }, { "offsetInBeginSection": 18, "offsetInEndSection": 169, "text": "OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a life-saving system used for critically ill patients with cardiac and/or respiratory failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28948652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Extracorporeal membrane oxygenation (ECMO) use in adults is rapidly increasing in its use for both cardiac and respiratory failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27113690", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 232, "text": "Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23406535", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 140, "text": "Access to centers with extracorporeal membrane oxygenation (ECMO) capabilities varies by region and may affect overall outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32092196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Extracorporeal membrane oxygenation (ECMO) is the short-term (days to weeks) support of patients with severe respiratory and/or cardiac failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25711946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Extracorporeal membrane oxygenation (ECMO) is a temporary technique for providing life support for cardiac dysfunction, pulmonary dysfunction, or both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25789816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Extracorporeal membrane oxygenation (ECMO) is a method of life support to maintain cardiopulmonary function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24651227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a form of life support that targets the hear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25608845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Extracorporeal membrane oxygenation (ECMO) is used to support patients with cardiopulmonary failure in the intensive care unit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19806801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Extracorporeal Membrane Oxygenation (ECMO) represents a useful tool to support the lungs and the heart when all conventional therapies failed and the patients are at risk of death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28533721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Extracorporeal membrane oxygenation (ECMO) support is a logical means of providing time for the acutely damaged lung to heal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/895593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Extracorporeal membrane oxygen (ECMO) has been used for many years in patients with life-threatening hypoxaemia and/or hypercarbia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25176974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a form of long-term cardiopulmonary bypass used to treat infants, children, and adults with respiratory and/or cardiac failure despite maximal medi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19088593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "BACKGROUND: Neonatal extracorporeal membrane oxygenation (ECMO) is a lifesaving therapeutic approach in newborns suffering from severe, but potentially reversible, respiratory insufficiency, mostly complicated by neonatal persistent pulmonary h", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23817232", "endSection": "abstract" } ] }, { "body": "Which diseases are associated with the Yaa gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15634937", "http://www.ncbi.nlm.nih.gov/pubmed/9862363", "http://www.ncbi.nlm.nih.gov/pubmed/9754557", "http://www.ncbi.nlm.nih.gov/pubmed/9743333", "http://www.ncbi.nlm.nih.gov/pubmed/7930846", "http://www.ncbi.nlm.nih.gov/pubmed/1537372", "http://www.ncbi.nlm.nih.gov/pubmed/8181531", "http://www.ncbi.nlm.nih.gov/pubmed/8040305", "http://www.ncbi.nlm.nih.gov/pubmed/18521959", "http://www.ncbi.nlm.nih.gov/pubmed/10753498", "http://www.ncbi.nlm.nih.gov/pubmed/7843228", "http://www.ncbi.nlm.nih.gov/pubmed/12594250", "http://www.ncbi.nlm.nih.gov/pubmed/16777955", "http://www.ncbi.nlm.nih.gov/pubmed/2599002" ], "ideal_answer": [ "The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease. It has also been shown to be associated with various autoimmune conditions such as lupus-like syndrome, collagen induced arthrits and glomerulonephritis.", "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus, maids, rheumatoid arthritis, arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, and lupUS-like nephitis.", "The Yaa gene-mediated acceleration of murine lupus: Yaa- T cells from non-autoimmune mice collaborate with Yaa+ B cells to produce Lupus autoantibodies in vivo.", "The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease.", "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus,maids, rheumatoid arthritis, arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, lUPus-like nephitis and other inflammatory bowel diseases.", "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus,maids, rheumatoid arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, lUPus and lupUS-like nephitis.", "F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa.", " Yaa is a Y-chromosome-linked gene that accelerates autoimmune diseases in some autoimmune-prone strains of mice The role of the Yaa gene in lupus syndrome The Y chromosome-linked \"autoimmune accelerating\" yaa gene suppresses collagen-induced arthritis", "Yaa is a Y-chromosome-linked gene that accelerates autoimmune diseases in some autoimmune-prone strains of mice . BXSB mice spontaneously develop a lupus-like syndrome that is accelerated by the Yaa gene . Yaa mice bearing the NZB chromosome 13 locus displayed increased serum gp70 production, but not glomerulonephritis .", "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus, maids, rheumatoid arthritis, arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, and lUPus-like nephitis.", "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus,maids, rheumatoid arthritis, l upus nephritis and murine acquired immunodeficiency syndrome." ], "exact_answer": [ [ "lupus" ], [ "lupus-like syndrome" ], [ "collagen-induced arthritis" ], [ "glomerulonephritis" ] ], "type": "list", "id": "5fdb84f2a43ad31278000030", "snippets": [ { "offsetInBeginSection": 255, "offsetInEndSection": 367, "text": " Yaa is a Y-chromosome-linked gene that accelerates autoimmune diseases in some autoimmune-prone strains of mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10753498", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1108, "text": "Yaa mice bearing the NZB chromosome 13 locus displayed increased serum gp70 production, but not gp70 IC formation and glomerulonephritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15634937", "endSection": "abstract" }, { "offsetInBeginSection": 615, "offsetInEndSection": 671, "text": "Yaa congenic mice, each carrying one individual NZB QTL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15634937", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 345, "text": "Male (NZW x BXSB)F1 mice, carrying the BXSB Yaa gene, serve as a model for SLE-associated antiphospholipid syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9754557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BXSB mice spontaneously develop a lupus-like syndrome that is accelerated by the Yaa gene (Y-linked autoimmune accelerator).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9743333", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 364, "text": "F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9862363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "The role of the Yaa gene in lupus syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7930846", "endSection": "title" }, { "offsetInBeginSection": 660, "offsetInEndSection": 739, "text": "It is intriguing that the Yaa gene effect is selective on autoimmune responses,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7930846", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "The Y chromosome-linked \"autoimmune accelerating\" yaa gene suppresses collagen-induced arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8181531", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8181531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "The role of the Yaa gene in lupus syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7930846", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The BXSB Y chromosome-linked mutant gene, Yaa, accelerates the progression of a lupus-like autoimmune syndrome only in mice that are predisposed to autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7843228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The accelerated development of systemic lupus erythematosus (SLE) in BXSB male mice is associated with the presence of an as yet unidentified mutant gene, Yaa (Y-linked autoimmune acceleration).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12594250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The accelerated development of systemic lupus erythematosus (SLE) in BXSB male mice is associated with the presence of an as yet unidentified mutant gene, Yaa (Y-linked autoimmune acceleration). In vi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12594250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8181531", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 534, "text": "ompared the clinical development (autoantibody production and glomerulonephritis) of systemic lupus erythematosus (SLE) in these three F1 hybrids in the presence or absence of the mutant gene, Yaa (Y chromosome-linked autoimmune acceleration), which normally accelerates the progression of murine SLE. (NZB x BXSB)F1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8040305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The Y-linked autoimmune accelerating (Yaa) locus drives the transition to fatal lupus nephritis when combined with B6.Sle1 in our C57BL/6J (B6)-congenic model of systemic autoimmunity. We a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18521959", "endSection": "abstract" }, { "offsetInBeginSection": 443, "offsetInEndSection": 652, "text": " are not overtly autoimmune, but the addition of Sle1, which contains the autoimmune-predisposing Slam/Cd2 haplotype, causes the development of fatal lupus with numerous immunological aberrations. B6.Sle1yaa C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16777955", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "By assessing the development of Y-linked autoimmune acceleration (Yaa) gene-induced systemic lupus erythematosus in C57BL/6 (B6) x (New Zealand Black (NZB) x B6.Yaa)F(1) backcross male mice, we mapped three major susceptibility loci derived from the NZB strain. These thre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15634937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "By assessing the development of Y-linked autoimmune acceleration (Yaa) gene-induced systemic lupus erythematosus in C57BL/6 (B6) x (New Zealand Black (NZB) x B6.Yaa)F(1) backcross male mice, we mapped three major susceptibility loci derived from the NZB strain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15634937", "endSection": "abstract" }, { "offsetInBeginSection": 1393, "offsetInEndSection": 1710, "text": "Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2599002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Linkage of a major quantitative trait locus to Yaa gene-induced lupus-like nephritis in (NZW x C57BL/6)F1 mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9862363", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 364, "text": "In the present study, we mapped the major quantitative trait loci (QTL) differing between the NZW and C57BL/6 inbred strains of mice by making use of (NZW x C57BL/6.Yaa)F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9862363", "endSection": "abstract" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1181, "text": "Our study thus provides a model to dissect the complex genetic interactions that result in manifestations of murine lupus-like disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9862363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The Yaa gene abrogates the major histocompatibility complex association of murine lupus in (NZB x BXSB)F1 hybrid mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8040305", "endSection": "title" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1232, "text": "These data indicate that (a) the conventional H-2b is a haplotype leading to susceptibility for murine SLE, while H-2d is a relatively resistant haplotype; (b) the H-2b haplotype exhibits a dominant effect on autoimmune responses, similar to the classical MHC-linked Ir gene effect; and (c) most strikingly, the Yaa gene totally abrogates the MHC effect on murine lupus in (NZB x BXSB)F1 hybrid mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8040305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1537372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8181531", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1502, "text": "The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1537372", "endSection": "abstract" } ] }, { "body": "Which receptors does bimagrumab block?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30095981" ], "ideal_answer": [ "Bimagrumab blocks the activin type II receptors." ], "exact_answer": [ "activin type II receptors" ], "type": "factoid", "id": "602c1d3b1cb411341a00011e", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 185, "text": "Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" } ] }, { "body": "Are PDXK mutations linked to polyneuropathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "http://www.ncbi.nlm.nih.gov/pubmed/32522499" ], "ideal_answer": [ "Yes, PDXK mutations are linked to polyneuropathy.", "Yes, PDXK mutations are associated with autosomal recessive polyneuropathy.", "Yes. PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.", "Yes, PDXK mutations are associated with delayed polyneuropathy.", "Yes, point mutations in PDXK gene may be associated with peripheral neuropathy." ], "exact_answer": "yes", "type": "yesno", "id": "6031002d1cb411341a000129", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 1971, "text": "To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy.METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification.RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization.INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225-240.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "endSection": "abstract" }, { "offsetInBeginSection": 1483, "offsetInEndSection": 1656, "text": "RETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We sh", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32522499", "endSection": "title" }, { "offsetInBeginSection": 1477, "offsetInEndSection": 1650, "text": "INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 901, "text": "RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "endSection": "abstract" }, { "offsetInBeginSection": 1496, "offsetInEndSection": 1653, "text": "show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187503", "endSection": "abstract" } ] }, { "body": "Is avelumab effective for urothelial carcinoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31807039", "http://www.ncbi.nlm.nih.gov/pubmed/32135514", "http://www.ncbi.nlm.nih.gov/pubmed/29217288", "http://www.ncbi.nlm.nih.gov/pubmed/32945632", "http://www.ncbi.nlm.nih.gov/pubmed/30004857", "http://www.ncbi.nlm.nih.gov/pubmed/32762233", "http://www.ncbi.nlm.nih.gov/pubmed/29103968", "http://www.ncbi.nlm.nih.gov/pubmed/30481100", "http://www.ncbi.nlm.nih.gov/pubmed/28585615", "http://www.ncbi.nlm.nih.gov/pubmed/31553054", "http://www.ncbi.nlm.nih.gov/pubmed/33037118", "http://www.ncbi.nlm.nih.gov/pubmed/32146152", "http://www.ncbi.nlm.nih.gov/pubmed/28375787", "http://www.ncbi.nlm.nih.gov/pubmed/31286802", "http://www.ncbi.nlm.nih.gov/pubmed/31940998", "http://www.ncbi.nlm.nih.gov/pubmed/30021426", "http://www.ncbi.nlm.nih.gov/pubmed/29540084" ], "ideal_answer": [ "Yes. Avelumab is an anti-programmed death-ligand 1 monoclonal antibody that is approved for the treatment of urothelial carcinoma." ], "exact_answer": "yes", "type": "yesno", "id": "601d76131cb411341a000044", "snippets": [ { "offsetInBeginSection": 530, "offsetInEndSection": 644, "text": "ince then, additional checkpoint inhibitors, including avelumab, durvalumab, and nivolumab, have gained approval. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31940998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10\u00a0mg/kg weight-based dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31553054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Five new PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma (UC): pembrolizumab, atezolizumab, durvalumab, nivolumab, and avelumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32135514", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 553, "text": "We reviewed the literature for prospective studies evaluating PD-1/PD-L1 inhibitors in refractory urothelial carcinoma patients, which formed the basis for US Food and Drug Administration approval of 5 different antagonistic antibodies targeting PD-1 or PD-L1 (atezolizumab, durvalumab, avelumab, nivolumab, and pembrolizumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32146152", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 997, "text": "Nowadays, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US FDA) for the first- or second-line use in urothelial carcinoma, based on durable response and manageable safety profiles observed in relevant clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32762233", "endSection": "abstract" }, { "offsetInBeginSection": 3179, "offsetInEndSection": 3392, "text": "RETATION: Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients. These", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217288", "endSection": "abstract" }, { "offsetInBeginSection": 3393, "offsetInEndSection": 3571, "text": "data provide the rationale for therapeutic use of avelumab in metastatic urothelial carcinoma and it has received accelerated US FDA approval in this setting on this basis.FUNDIN", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "BACKGROUND: Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33037118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33037118", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29103968", "endSection": "abstract" }, { "offsetInBeginSection": 2027, "offsetInEndSection": 2281, "text": "SIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Fund", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32945632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28585615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10\u00a0mg/kg weight-based dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31553054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma. Accor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28585615", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 778, "text": "ACQUISITION: Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PD-L1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in first- and second-line treatment setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30021426", "endSection": "abstract" }, { "offsetInBeginSection": 3173, "offsetInEndSection": 3386, "text": "INTERPRETATION: Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217288", "endSection": "abstract" }, { "offsetInBeginSection": 1905, "offsetInEndSection": 2047, "text": "Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28375787", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Avelumab: A Novel Anti-PD-L1 Agent in the Treatment of Merkel Cell Carcinoma and Urothelial Cell Carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30004857", "endSection": "title" }, { "offsetInBeginSection": 692, "offsetInEndSection": 829, "text": "In early 2017, avelumab (BAVENCIO\u00ae), a PD-L1-blocking monoclonal antibody agent, was approved for the treatment of metastatic MCC and UC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30004857", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1024, "text": "Expert opinion: Avelumab has shown clinical efficacy for metastatic and advanced UC in phase I studies after the failure of platinum-based therapy with a well-tolerated safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31286802", "endSection": "abstract" }, { "offsetInBeginSection": 598, "offsetInEndSection": 811, "text": "Avelumab has been approved by the U.S. FDA for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma that has progressed during or following treatment with a platinum-based regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30481100", "endSection": "abstract" } ] }, { "body": "What tissues have been studied by circadian proteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17726681", "http://www.ncbi.nlm.nih.gov/pubmed/30973132", "http://www.ncbi.nlm.nih.gov/pubmed/31034157" ], "ideal_answer": [ "Retina\nLiver" ], "exact_answer": [ [ "Retina" ], [ "Liver" ] ], "type": "list", "id": "603221741cb411341a000136", "snippets": [ { "offsetInBeginSection": 288, "offsetInEndSection": 463, "text": " In peripheral organs, such as the liver, the circadian clock coordinates gene expression, notably metabolic gene expression, from transcriptional to posttranslational level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31034157", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "Circadian proteomics of the mouse retina.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17726681", "endSection": "title" }, { "offsetInBeginSection": 496, "offsetInEndSection": 662, "text": " In addition, the analysis of rhythmic post-translational modifications helps to understand the signal pathways involved and their consequences on hepatic metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30973132", "endSection": "abstract" } ] }, { "body": "Is MIS-C or Multisystem Inflammatory syndrome in children a complication of Covid-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33278107", "http://www.ncbi.nlm.nih.gov/pubmed/33300011", "http://www.ncbi.nlm.nih.gov/pubmed/32925547", "http://www.ncbi.nlm.nih.gov/pubmed/32463092", "http://www.ncbi.nlm.nih.gov/pubmed/33042918", "http://www.ncbi.nlm.nih.gov/pubmed/32631771", "http://www.ncbi.nlm.nih.gov/pubmed/33180935", "http://www.ncbi.nlm.nih.gov/pubmed/32953455", "http://www.ncbi.nlm.nih.gov/pubmed/32532619", "http://www.ncbi.nlm.nih.gov/pubmed/32755212", "http://www.ncbi.nlm.nih.gov/pubmed/33263635", "http://www.ncbi.nlm.nih.gov/pubmed/32935083", "http://www.ncbi.nlm.nih.gov/pubmed/33055501", "http://www.ncbi.nlm.nih.gov/pubmed/32946801", "http://www.ncbi.nlm.nih.gov/pubmed/32827525", "http://www.ncbi.nlm.nih.gov/pubmed/33042116", "http://www.ncbi.nlm.nih.gov/pubmed/33011038", "http://www.ncbi.nlm.nih.gov/pubmed/32496723", "http://www.ncbi.nlm.nih.gov/pubmed/33180050", "http://www.ncbi.nlm.nih.gov/pubmed/33110725", "http://www.ncbi.nlm.nih.gov/pubmed/33083367", "http://www.ncbi.nlm.nih.gov/pubmed/33243303", "http://www.ncbi.nlm.nih.gov/pubmed/32923992", "http://www.ncbi.nlm.nih.gov/pubmed/32837148", "http://www.ncbi.nlm.nih.gov/pubmed/33295957", "http://www.ncbi.nlm.nih.gov/pubmed/32839782", "http://www.ncbi.nlm.nih.gov/pubmed/32493734", "http://www.ncbi.nlm.nih.gov/pubmed/33269352", "http://www.ncbi.nlm.nih.gov/pubmed/33263756", "http://www.ncbi.nlm.nih.gov/pubmed/32975439", "http://www.ncbi.nlm.nih.gov/pubmed/32995826", "http://www.ncbi.nlm.nih.gov/pubmed/32966765", "http://www.ncbi.nlm.nih.gov/pubmed/33217259", "http://www.ncbi.nlm.nih.gov/pubmed/32511374" ], "ideal_answer": [ "Is MIS-C or Multisystem Inflammatory Syndrome in children a complication of Covid-19? Yes, it is.", "Multisystem Inflammatory syndrome AKA MIS-C is a complication of Covid-19 infection in children.", "Multisystem inflammatory syndrome in children (MIS-C) is a complication of Covid-19, clinically characterized by severe chronic inflammation in the central nervous system of children and adolescents." ], "exact_answer": "yes", "type": "yesno", "id": "601dc46c1cb411341a000050", "snippets": [ { "offsetInBeginSection": 150, "offsetInEndSection": 348, "text": "Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32493734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32463092", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "COVID-19 and Multisystem Inflammatory Syndrome in Latin American Children", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33055501", "endSection": "title" }, { "offsetInBeginSection": 94, "offsetInEndSection": 203, "text": " This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33055501", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 354, "text": "A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6\u00a0weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32966765", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 1020, "text": "We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T\u00a0cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32966765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32946801", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 558, "text": "This syndrome is now known as either \"Pediatric Inflammatory Multisystem Syndrome temporally related with COVID-19\" (PIMS-TS) (1), or Multisystem Inflammatory Syndrome in Children (MIS-C) (2) and is currently considered a rare post-COVID-19 complication which, in a minority of cases, can lead to death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33042918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized condition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. Thes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32511374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Background: Kawasaki-like syndrome occurring in children during the COVID-19 pandemic has been labelled multisystem inflammatory syndrome in children (MIS-C) by the CDC and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) by ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33083367", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 660, "text": "em inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This revie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33263635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "BACKGROUND: A small subset of pediatric patients develop a rare syndrome associated with Coronavirus Disease 2019 (COVID-19) infection called multisystem inflammatory syndrome in childr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33011038", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 383, "text": " adults. However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complicat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32975439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33243303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early tr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32946801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Background: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923992", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 469, "text": "Recent COVID-19 publications describe a variety of clinical presentations including an asymptomatic state, pneumonia, a hemophagocytic lymphohistiocytosis like syndrome, Multisystem Inflammatory Syndrome in Children (MIS-C) but, also called Pediatric Inflammatory Multisystem Syndrome-Toxic Shock (PIMS-TS), Kawasaki Disease, and myocarditis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33042116", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 743, "text": "We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32995826", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 649, "text": "Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33263635", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 741, "text": "It includes a discussion of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, as well as other aspects of the COVID-19 pandemic that are affecting children and families, such as poisonings, childhood immunizations, mental health, nonaccidental trauma, and neglect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32496723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 827, "text": "Importance: To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms.Objective: To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020.Design, Setting, and Participants: A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C.Main Outcomes and Measures: Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33295957", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 822, "text": "This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation.Methods: We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries.Results: Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32935083", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 632, "text": "DESIGN: Children ages 0-22\u00a0years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32827525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33269352", "endSection": "abstract" }, { "offsetInBeginSection": 308, "offsetInEndSection": 805, "text": "METHODS: An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32925547", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 353, "text": "Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33263756", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 353, "text": "Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32839782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Data on multisystem inflammatory syndrome in children (MIS-C) related to coronavirus disease-19 (COVID-19) is increasing in the current COVID-19 pandemic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32953455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Introduction Multisystem inflammatory syndrome in children (MIS-C) is a unique clinical complication of SARS-CoV-2 infection observed in pediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33180050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33180050", "endSection": "title" }, { "offsetInBeginSection": 403, "offsetInEndSection": 764, "text": "Case presentation An eight-year-old female presented with hyperglycemia, ketosis and metabolic acidosis consistent with diabetic ketoacidosis (DKA) in the setting of fever, rash, respiratory distress, hemodynamic instability, reduced systolic function with dilation of the left anterior descending artery, and positive SARS-CoV-2 antibodies suggestive of MIS-C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33180050", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 389, "text": "However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complications.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32975439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Toxic shock-like syndrome and COVID-19: Multisystem inflammatory syndrome in children (MIS-C).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32532619", "endSection": "title" }, { "offsetInBeginSection": 366, "offsetInEndSection": 588, "text": "Many of these cases feature a toxic shock-like syndrome or Kawasaki-like syndrome in the setting of SARS-CoV-2 positive diagnostic testing and the CDC has termed this presentation Multisystem Inflammatory Syndrome (MIS-C).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32532619", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1113, "text": "We describe a case of MIS-C in a child who presented to our Emergency Department (ED) twice and on the second visit was found to have signs of distributive shock, multi-organ injury and systemic inflammation associated with COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32532619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "PURPOSE OF REVIEW: Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases.RECENT FINDINGS: Clinical presentation of MIS-C is do", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33278107", "endSection": "abstract" }, { "offsetInBeginSection": 1471, "offsetInEndSection": 1618, "text": "MIS-C is a rare yet severe and highly critical complication of COVID-19 infection in pediatrics, leading to serious and life-threatening illnesses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33110725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "BACKGROUND: A multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) has recently been described.OBJECTIVE: To evaluate imaging findings of MIS-C associated with COVID-19.SUBJECTS AND METHODS: Imaging studies and medical records of sixteen patients (0-20 years) admit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "BACKGROUND: Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been reporte", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33180935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Recent reports have described a secondary Multisystem Inflammatory Syndrome in Children (MIS-C) after a prior COVID-19 infection that often has features of Kawasaki disease (KD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32631771", "endSection": "abstract" }, { "offsetInBeginSection": 2022, "offsetInEndSection": 2447, "text": " discharged home (length of hospital stay 3-20 days). There were no mortalities.CONCLUSION: MIS-C associated with COVID-19 is characterized predominantly by cardiovascular abnormalities, though also solid visceral organ, gallbladder, and bowel abnormalities as well as ascites, reflecting a multisystemic inflammatory process.CLINICAL IMPACT: The constellation of imaging findings in the setting of COVID-19 may alert pediatr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Multisystem Inflammatory Syndrome in Children Temporally Related to COVID-19: A Case Report From Saudi Arabia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33110725", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33243303", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 598, "text": "ric patients. An association between COVID-19 and a Kawasaki-like inflammatory syndrome has recently presented in pediatric patients.CASE REPORT: We report a unique case of multisystem inflammatory syndrome in children presenting with characteristic findings in a child who later developed cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.CONCLUSION: Recognition of these early signs and symptoms facilitates screening and risk stratification of pediatric COVID-19 cas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33217259", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Severe cardiac dysfunction in a patient with multisystem inflammatory syndrome in children associated with COVID-19: Retrospective diagnosis of a puzzling presentation. A case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32837148", "endSection": "title" } ] }, { "body": "Which RNA polymerase transcribes enhancer RNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27662874", "http://www.ncbi.nlm.nih.gov/pubmed/30448228", "http://www.ncbi.nlm.nih.gov/pubmed/28533025", "http://www.ncbi.nlm.nih.gov/pubmed/27662872", "http://www.ncbi.nlm.nih.gov/pubmed/32060325", "http://www.ncbi.nlm.nih.gov/pubmed/3299107", "http://www.ncbi.nlm.nih.gov/pubmed/26319018", "http://www.ncbi.nlm.nih.gov/pubmed/29378668", "http://www.ncbi.nlm.nih.gov/pubmed/3462718", "http://www.ncbi.nlm.nih.gov/pubmed/26864944", "http://www.ncbi.nlm.nih.gov/pubmed/2218723", "http://www.ncbi.nlm.nih.gov/pubmed/31824865", "http://www.ncbi.nlm.nih.gov/pubmed/26219400", "http://www.ncbi.nlm.nih.gov/pubmed/20393465", "http://www.ncbi.nlm.nih.gov/pubmed/3031599", "http://www.ncbi.nlm.nih.gov/pubmed/25578728", "http://www.ncbi.nlm.nih.gov/pubmed/24599251", "http://www.ncbi.nlm.nih.gov/pubmed/2986013" ], "ideal_answer": [ "Analogously to mRNAs, the non-protein-encoding enhancer RNAs are synthesized by RNA Pol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail.", "Enhancers are bound by sequence-specific transcription factors, which in turn facilitate the cooperative binding of chromatin remodeling enzymes, histone modifying enzymes, other co-factors, and ultimately the RNA polymerase II complex (RNA pol II). Both the target genes and the enhancers are transcribed by RNA pol II.", "Analogously to mRNAs, the non-protein-encoding enhancer RNAs are synthesized by RNA Pol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail. Recent evidence indicates that miRNA genes are transcribed by RNA polymerase II (Pol II)", "Enhancer RNAs (eRNAs) are a group of lncRNAs transcribed from enhancers by RNA Polymerase II.", "Analogously to mRNAs, the non-protein-encoding enhancers are synthesized by RNA polymerase II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail. Recent evidence indicates that miRNA genes are transcribed by RNA Pol II (Pol II)", "Because the transcripts of most enhancer genes are the products of type-II RNA polymerase, enhancer RNA Pol II (Pol II) has a poly(A) tail and appears in expressed sequence tags (EST). Analogously to mRNAs, the non-protein-encoding enhancer RNAs (ncRNAs) are synthesized by RNAPol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tails.", "Because the transcripts of most enhancers are the products of type-II RNA polymerase, enhancer RNA Pol II (Pol II) has a poly(A) tail and appears in expressed sequence tags (EST). Analogously to mRNAs, the non-protein-encoding enhancer RNAs are synthesized by RNAPol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly ( A) tail.", "The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP." ], "exact_answer": [ "RNA polymerase II", "RNA polII", "RNAPII" ], "type": "factoid", "id": "5fe3131ba43ad31278000047", "snippets": [ { "offsetInBeginSection": 689, "offsetInEndSection": 894, "text": "Remarkably, we found that in response to E2 TDG localized to enhancers which also recruit ER\u03b1, RNA Pol II and other coregulators and which are marked by histone modifications indicative of active enhancers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29378668", "endSection": "abstract" }, { "offsetInBeginSection": 862, "offsetInEndSection": 1075, "text": "The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26864944", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 162, "text": "Enhancer RNAs (eRNAs) are a group of lncRNAs transcribed from enhancers, whose regulatory effects on gene expression are an emerging area of interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30448228", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 556, "text": "The expression of genes targeted by transcribing enhancer is positively correlated with eRNA expression and significantly higher than expression of genes targeted by non-transcribing enhancers. This result implies eRNA transcription indicates a state of enhancer that further increases gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26219400", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 518, "text": "In the light of these results it was surprising to find that the 5' flanking region of a mouse U6 RNA gene includes a perfect copy of the octamer sequence motif, ATTTGCAT, found in many RNA polymerase II transcription enhancer elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3299107", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1229, "text": "Since transcription of these aberrant RNAs is stimulated by the addition of a murine sarcoma virus enhancer segment, they are probably transcribed by RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3462718", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 399, "text": "Recent studies have shown that active enhancers recruit RNA polymerase II (Pol II) and are transcribed, producing enhancer RNAs (eRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27662874", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 941, "text": "Inspection of X. tropicalis, mouse and human U6 DNA upstream sequences revealed the presence of a TATA box as well as of the proximal and enhancer (octamer motif) elements contained in snRNA genes transcribed by RNA polymerase II.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3031599", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 480, "text": "ancer RNAs (eRNAs) are non-coding RNAs transcribed from enhancers that function to promote the enhancer's functions via multiple mechanisms, such as recruiting transcription factors to specific enhancers, promoting enhancer-promoter looping, directing chromatin accessibility, interacting with RNA polymerase II and facilitating histone acetylation. Understa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31824865", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 439, "text": "uch regulatory elements often bypass intervening genes and typically comprise binding sites for multiple transcription factors that can also be transcribed by RNA polymerase II (Pol II) to produce noncoding enhancer RNAs (eRNAs). G", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24599251", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 403, "text": "cent studies have shown that active enhancers recruit RNA polymerase II (Pol II) and are transcribed, producing enhancer RNAs (eRNAs). GRO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27662874", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 632, "text": "ly, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The le", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20393465", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 649, "text": "sociates broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from snRNA and replication-dependent histone genes. Within pre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25578728", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 1030, "text": "As (eRNAs), and recruit RNA polymerase II as well as RAD21, a member of the cohesin complex involved in chromatin interactions between enhancers and promoters. Importantly, their rec", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26319018", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 625, "text": "Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20393465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Enhancer-derived RNAs (eRNAs) are a group of RNAs transcribed by RNA polymerase II from the domain of transcription enhancers, a major type of cis-regulatory elements in the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28533025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Enhancers stimulate transcription of RNA polymerase II-transcribed genes in an orientation-independent manner and over long distances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2218723", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Recent work has shown that RNA polymerase II-mediated transcription at distal cis-regulatory elements serves as a mark of highly active enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27662872", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 584, "text": "Based on some reports on RNA polymerase I transcription, we wanted to test whether RNA polymerase II enters at the enhancer and from there proceeds towards the promoter while synthesizing unstable transcripts (\"scanning/readthrough transcription\" model).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2218723", "endSection": "abstract" }, { "offsetInBeginSection": 814, "offsetInEndSection": 955, "text": "We show here that the SV40 enhancer acts at least in part to increase the number of RNA polymerase II molecules transcribing the linked gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2986013", "endSection": "abstract" } ] }, { "body": "Name the three phase 3, randomized, double-blind, placebo-controlled that assessed galcanezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32319039" ], "ideal_answer": [ "Galcanezumab has been assessed in the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2 and REGAIN studies." ], "exact_answer": [ [ "EVOLVE-1" ], [ "EVOLVE-2" ], [ "REGAIN" ] ], "type": "list", "id": "602900aa1cb411341a000107", "snippets": [ { "offsetInBeginSection": 1061, "offsetInEndSection": 1367, "text": "Data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2 and REGAIN studies show that galcanezumab treatment for 3 or 6\u00a0months results in overall reduction in mean monthly migraine headache days in patients with episodic (EVOLVE-1 and EVOLVE-2) and chronic (REGAIN) migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32319039", "endSection": "abstract" } ] }, { "body": "Is co-loss of BRCA2-RB1 associated with better prognosis for prostate cancer patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31796516" ], "ideal_answer": [ "No. Co-loss of BRCA2-RB1 in human prostate cancer cells induces an epithelial-to-mesenchymal transition, which is associated with invasiveness and a more aggressive disease phenotype." ], "exact_answer": "no", "type": "yesno", "id": "6020010a1cb411341a00007c", "snippets": [ { "offsetInBeginSection": 1129, "offsetInEndSection": 1767, "text": "In human prostate cancer cell lines (LNCaP and LAPC4), loss of BRCA2 leads to the castration-resistant phenotype. Co-loss of BRCA2-RB1 in human prostate cancer cells induces an epithelial-to-mesenchymal transition, which is associated with invasiveness and a more aggressive disease phenotype. Importantly, PARP inhibitors attenuate cell growth in human mCRPC-derived organoids and human CRPC cells harboring single-copy loss of both genes.CONCLUSIONS: Our findings suggest that early identification of this aggressive form of prostate cancer offers potential for improved outcomes with early introduction of PARP inhibitor-based therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31796516", "endSection": "abstract" } ] }, { "body": "Which drugs were investigated in the ALPHEUS trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32473356", "http://www.ncbi.nlm.nih.gov/pubmed/33202219" ], "ideal_answer": [ "ALPHEUS study examined if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective percutaneous coronary intervention (PCI)." ], "exact_answer": [ [ "ticagrelor" ], [ "clopidogrel" ] ], "type": "list", "id": "60273a161cb411341a0000d8", "snippets": [ { "offsetInBeginSection": 629, "offsetInEndSection": 973, "text": "METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32473356", "endSection": "abstract" }, { "offsetInBeginSection": 1659, "offsetInEndSection": 1889, "text": "CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32473356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202219", "endSection": "title" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1076, "text": ". Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202219", "endSection": "abstract" }, { "offsetInBeginSection": 2243, "offsetInEndSection": 2473, "text": ".INTERPRETATION: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202219", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 520, "text": "The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202219", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 1018, "text": "oading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized b", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32473356", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 521, "text": "The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202219", "endSection": "abstract" }, { "offsetInBeginSection": 1488, "offsetInEndSection": 1856, "text": " elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier).CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32473356", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 951, "text": "e patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting.METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32473356", "endSection": "abstract" } ] }, { "body": "Which cell secretes the enzyme tryptase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31709696", "http://www.ncbi.nlm.nih.gov/pubmed/31858758", "http://www.ncbi.nlm.nih.gov/pubmed/31853339" ], "ideal_answer": [ "Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines." ], "exact_answer": [ "Mast cells" ], "type": "factoid", "id": "6048ff3e1cb411341a000160", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 168, "text": "Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31709696", "endSection": "abstract" }, { "offsetInBeginSection": 835, "offsetInEndSection": 867, "text": "MCs markers (Fc\u03b5RI and tryptase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31853339", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 815, "text": "Tryptase-positive MC ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31858758", "endSection": "abstract" } ] }, { "body": "What disease does BCG immunotherapy used to treat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31755155", "http://www.ncbi.nlm.nih.gov/pubmed/23517232", "http://www.ncbi.nlm.nih.gov/pubmed/29576423", "http://www.ncbi.nlm.nih.gov/pubmed/12084297", "http://www.ncbi.nlm.nih.gov/pubmed/10575270", "http://www.ncbi.nlm.nih.gov/pubmed/26032289", "http://www.ncbi.nlm.nih.gov/pubmed/27241256", "http://www.ncbi.nlm.nih.gov/pubmed/28488840", "http://www.ncbi.nlm.nih.gov/pubmed/26000263", "http://www.ncbi.nlm.nih.gov/pubmed/31900581", "http://www.ncbi.nlm.nih.gov/pubmed/4412271", "http://www.ncbi.nlm.nih.gov/pubmed/6342739", "http://www.ncbi.nlm.nih.gov/pubmed/18976938", "http://www.ncbi.nlm.nih.gov/pubmed/15281319", "http://www.ncbi.nlm.nih.gov/pubmed/7016300", "http://www.ncbi.nlm.nih.gov/pubmed/31307960", "http://www.ncbi.nlm.nih.gov/pubmed/24064971", "http://www.ncbi.nlm.nih.gov/pubmed/19957324", "http://www.ncbi.nlm.nih.gov/pubmed/12057150", "http://www.ncbi.nlm.nih.gov/pubmed/178234", "http://www.ncbi.nlm.nih.gov/pubmed/30893148", "http://www.ncbi.nlm.nih.gov/pubmed/9259090", "http://www.ncbi.nlm.nih.gov/pubmed/27960233", "http://www.ncbi.nlm.nih.gov/pubmed/1244548", "http://www.ncbi.nlm.nih.gov/pubmed/8573479", "http://www.ncbi.nlm.nih.gov/pubmed/19967427", "http://www.ncbi.nlm.nih.gov/pubmed/28807024", "http://www.ncbi.nlm.nih.gov/pubmed/32577059", "http://www.ncbi.nlm.nih.gov/pubmed/25794874" ], "ideal_answer": [ "Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy is used for treatment of bladder cancer.", "Bacillus Calmette- Gu\u00e9rin (BCG) immunotherapy is used for treatment of bladder cancer.", "Bacillus Calmette- Gu\u00e9rin (BCG) immunotherapy is used in the treatment of bladder cancer.", "BCG immunotherapy is the choice of care for high-grade non-muscle invasive bladder cancer (NMIBC) after transurethral resection.", "BCG immunotherapy is the choice of care for high-grade non-muscle invasive bladder cancer.", "Bacillus Calmette-gu\u00e9rin (BCG) immunotherapy is used in the treatment of bladder cancer." ], "exact_answer": [ "bladder cancer", "bladder cancer (NMIBC)", "high-grade non-muscle invasive bladder cancer (NMIBC)" ], "type": "factoid", "id": "60292d191cb411341a00010e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Bacillus Calmette-Gu\u00e9rin immunotherapy for bladder cancer: a review of immunological aspects, clinical effects and BCG infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31755155", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy for bladder cancer has been used since 1976 when the first evidence of its ability to lower recurrence and progression rates was published.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31755155", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 320, "text": "BCG immunotherapy is the choice of care for high-grade non-muscle invasive bladder cancer (NMIBC) after transurethral resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31755155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Renal Tuberculosis Following Intravesical Bacillus Calmette-Gu\u00e9rin (BCG) Immunotherapy for the Treatment of Bladder Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32577059", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Adjuvant BCG immunotherapy for stage I and II malignant melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6342739", "endSection": "title" }, { "offsetInBeginSection": 281, "offsetInEndSection": 455, "text": "Intravesical BCG (Bacillus Calmette-Guerin) immunotherapy has been widely used to treat NMIBC, but it fails to suppress recurrence of bladder tumors in up to 40% of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26032289", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 674, "text": "Presently, bacillus Calmette-Guerin (BCG) immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, Tl, CIS) and has positive outcomes on tumor recurrence rate, disease progression, and prolongation of survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9259090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24064971", "endSection": "title" }, { "offsetInBeginSection": 556, "offsetInEndSection": 655, "text": "Data support that BCG has a positive impact on tumor recurrence, disease progression, and survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12084297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "It is nearly 40 years since Bacillus Calmette-Gu\u00e9rin (BCG) was first used as an immunotherapy to treat superficial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26000263", "endSection": "abstract" }, { "offsetInBeginSection": 675, "offsetInEndSection": 938, "text": "Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with BCG intravesical immunotherapy-it has demonstrated a reduction in tumor recurrence rates, but has had no positive impact on disease progression or prolongation of survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9259090", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794874", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "The advantage of BCG immunotherapy over intravesical chemotherapy in superficial bladder cancer has been most apparent in patients with carcinoma in situ (CIS), where complete response is increased from 50% to more than 70% and the proportion of patients remaining disease free for 5 years is increased from 20% to 40%. Similar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15281319", "endSection": "abstract" }, { "offsetInBeginSection": 64, "offsetInEndSection": 310, "text": "dministration of Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy has become the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) and carcinoma in-situ (CIS) in terms of prevention of recurrence and progression. While most a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "OBJECTIVES: Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy is regarded as the current treatment of choice for stage T1 grade 3 (T1G3) bladder cancer (BC), though its efficacy is limited by high recurrence and progression ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18976938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Gu\u00e9rin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urolo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28807024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Intravesical Mycobacterium bovis bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Desp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19967427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "BACKGROUND: Intravesical immunotherapy with Mycobacterium bovis (M. bovis) bacillus Calmette-Guerin (BCG) is the current standard of care against superficial, high-grade transitional cell carcinoma (TCC) of the urinary bladder (carcinoma in situ and pathologic T1, grade 3 disease)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19957324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "It is nearly 40 years since Bacillus Calmette-Gu\u00e9rin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Des", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26000263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Intravesical immunotherapy with bacille Calmette-Gu\u00e9rin (BCG) vaccine is the main treatment for non-muscle-invasive bladder cancer (NMIBC), with proven effects on reducing recurrence, progression, and death from NMIBC. However", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31307960", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 810, "text": " propria invasive tumors and carcinoma in situ, intravesical immunotherapy with bacille Calmette-Gu\u00e9rin (BCG) is often the first line of treatment to decrease tumor recurrence and to possibly decrease progression and improve survival. Intravesical ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12057150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Base", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27241256", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 898, "text": "FINDINGS: Although BCG has been used to treat high-risk NMIBC for decades, new applications of immunotherapy include the use of exogenous cytokines to boost immune response, vaccines to activate the immune system against specific tumor-associated antigens, intravesical agents that cause generalized local inflammation, and targeted antibodies against proteins on the surface of immune checkpoint inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30893148", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 825, "text": "Drugs such as mitomycin C used after transurethral resection of bladder tumour to reduce recurrences, bacillus Calmette-Gu\u00e9rin (BCG) intravesical immunotherapy to treat high-risk non-muscle-invasive bladder cancer and urothelial CIS and platin-based systemic chemotherapy to improve postcystectomy disease-specific survival are examples of therapy-related atypia seen in the urinary tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27960233", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 728, "text": "Mitomycin C used after transurethral resection of bladder tumor to reduce recurrences, BCG intravesical immunotherapy to treat high risk non-muscle invasive bladder cancer and urothelial carcinoma in situ, and platinum-based systemic chemotherapy to improve post-cystectomy disease-specific survival some of the causes of therapy related atypia in urinary bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29576423", "endSection": "abstract" }, { "offsetInBeginSection": 1123, "offsetInEndSection": 1435, "text": "This comprehensive review highlights recent developments in intravesical therapy of bladder cancer and summarizes the mechanisms of action of BCG, and the important role of intravesical BCG immunotherapy and other immunotherapeutic agents in the therapy and prophylaxis of superficial TCC of the urinary bladder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9259090", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 841, "text": "The following two approaches to BCG immunotherapy were investigated at the Department of Urology of Padova University by specific Phase II and III trials designed to evaluate the possibility of reducing BCG-related side-effects without compromising therapeutic efficacy: (1) by reducing the dose of BCG per instillation 'low-dose' regimen, (2) by delaying the interval of the instillations 'slow-rate' regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10575270", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1491, "text": "This review summarises the history and development of BCG as a modern cancer treatment, appraises current optimal application of BCG immunotherapy in bladder cancer, discusses promising new therapies closely related to BCG, and briefly explores the possibility that BCG or related treatments may have an application in other urological malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517232", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 466, "text": "Immunotherapy by intravesicular delivery of Bacillus Calmette\u2013Gu\u00e9rin (BCG) is used to treat and prevent the recurrence of superficial bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28488840", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1141, "text": "Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy is currently the most effective treatment of non-muscle invasive bladder cancer and one of the most successful applications of immunotherapy to the treatment of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517232", "endSection": "abstract" }, { "offsetInBeginSection": 57, "offsetInEndSection": 297, "text": ": The administration of Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy has become the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) and carcinoma in-situ (CIS) in terms of prevention of recurrence and progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517232", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 927, "text": "The data establishing BCG immunotherapy as the standard of care for high-grade NMIBC and CIS over other bladder instillation modalities is presented in addition to the effect maintenance BCG therapy has on sustaining the immuno-protective effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517232", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 926, "text": "SUMMARY: When T1 high-grade non-muscle-invasive bladder cancer is persistent or recurs shortly after a full course of bacille Calmette-Gu\u00e9rin (BCG) plus maintenance, further BCG is not likely to work; this meets the new definition of a \"BCG unresponsive\" disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31307960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31900581", "endSection": "title" }, { "offsetInBeginSection": 1487, "offsetInEndSection": 1716, "text": "-treatment PD-L1 expression was associated with unfavorable pathological features in primary high-grade NMIBC and its expression level after BCG immunotherapy was significantly decreased in patients with refractory recurrence. PD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31900581", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 459, "text": "e reviewed a total of 141 high-grade NMIBC cases treated with transurethral resection\u2009+\u2009\u2009\u2265\u20096 BCG instillations between 2004 and 2017. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31900581", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 555, "text": "Presently, BCG is commonly used and is the most effective immunotherapeutic agent against superficial transitional cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12084297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Gu\u00e9rin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794874", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 510, "text": "Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794874", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 784, "text": "Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25794874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Adjuvant immunotherapy with BCG in treatment of regional-lymph-node metastases from malignant melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1244548", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "BCG immunotherapy for transitional-cell carcinoma in situ of the bladder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8573479", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "BCG immunotherapy of bladder cancer: inhibition of tumor recurrence and associated immune responses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7016300", "endSection": "title" }, { "offsetInBeginSection": 1056, "offsetInEndSection": 1173, "text": "Early experiences with BCG immunotherapy for malignant melanoma and C. parvum for oat cell carcinoma are encouraging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/178234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Bacillus Calmette-Gu\u00e9rin immunotherapy for genitourinary cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23517232", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Over the past 7 years, 151 patients with malignant melanoma have been treated with BCG immunotherapy alone or as an adjunct to surgical therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4412271", "endSection": "abstract" } ] }, { "body": "Which epigenetic marks are deposited by PRC1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27410265", "http://www.ncbi.nlm.nih.gov/pubmed/26151332", "http://www.ncbi.nlm.nih.gov/pubmed/21311219", "http://www.ncbi.nlm.nih.gov/pubmed/25071008", "http://www.ncbi.nlm.nih.gov/pubmed/19462008", "http://www.ncbi.nlm.nih.gov/pubmed/25754661", "http://www.ncbi.nlm.nih.gov/pubmed/27630184", "http://www.ncbi.nlm.nih.gov/pubmed/18974828", "http://www.ncbi.nlm.nih.gov/pubmed/26564795", "http://www.ncbi.nlm.nih.gov/pubmed/23706298" ], "ideal_answer": [ "PRC2 induces histone H3 lysine 27 (H3K27) trimethylation (H3K27me3), which is subsequently read by PRC1 that further catalyzes H2A monoubiquitination (H2Aub1), creating a transcriptional silent chromatin conformation.", "H2A monoubiquitination (H2Aub1), catalyzed by Polycomb-Repressive Complex1 (PRC1) is a key epigenetic mark in Polycomb silencing . Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase .", "Histone H2A monoubiquitination (H2Aub1), catalyzed by Polycomb-Repressive Complex1 (PRC1), is a key epigenetic mark in Polycomb silencing . Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase ." ], "exact_answer": [ "H2Aub1" ], "type": "factoid", "id": "5d35ee08b3a6380763000012", "snippets": [ { "offsetInBeginSection": 395, "offsetInEndSection": 571, "text": " In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27410265", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 694, "text": "When cells enter senescence the binding to RD of both PRC1 and PRC2 complexes is lost leading to a decreased level of histone H3K27 trimethylation (H3K27me3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19462008", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 518, "text": "PRC2 induces histone H3 lysine 27 (H3K27) trimethylation (H3K27me3), which is subsequently read by PRC1 that further catalyzes H2A monoubiquitination (H2Aub1), creating a transcriptional silent chromatin conformation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23706298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Histone H2A monoubiquitination (H2Aub1), catalyzed by Polycomb-Repressive Complex1 (PRC1), is a key epigenetic mark in Polycomb silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27630184", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 415, "text": "For a long time, the PcG mechanism has been proposed to follow a hierarchical recruitment of PcG repressive complexes (PRCs) to target genes in which the binding of PRC2 and the incorporation of H3 lysine 27 trimethyl marks led to recruitment of PRC1, which in turn mediated H2A monoubiquitination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25754661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Histone H2A monoubiquitination (H2Aub1), catalyzed by Polycomb-Repressive Complex1 (PRC1), is a key epigenetic mark in Polycomb silencing. Ho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27630184", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1352, "text": "Intriguingly, many promoters were co-regulated by all three histone marks, becoming hypermethylated with loss of H3K4me3 or H3K27me3 and hypomethylated with depletion of H2AK119ub, and many of these co-regulated loci were among those commonly targeted for aberrant hypermethylation in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071008", "endSection": "abstract" } ] }, { "body": "Does erenumab target the calcitonin gene-related peptide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30651064" ], "ideal_answer": [ "No, erenumab targets the calcitonin gene-related peptide receptor." ], "exact_answer": "no", "type": "yesno", "id": "6028ffae1cb411341a000106", "snippets": [ { "offsetInBeginSection": 142, "offsetInEndSection": 362, "text": "Four monoclonal antibodies have been developed: one targeting the calcitonin gene-related peptide receptor (erenumab) and three targeting the calcitonin gene-related peptide (eptinezumab, fremanezumab, and galcanezumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30651064", "endSection": "abstract" } ] }, { "body": "Which key gene is involved in interstitial 6q25 microdeletion syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26754677" ], "ideal_answer": [ "Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, these deletions are considered to be part of a unique microdeletion syndrome associated with intellectual disability and speech impairment, typical dysmorphic features, structural anomalies of the brain, microcephaly, and non-specific multiple organ anomalies. ARID1B is the key gene behind 6q microdeletion syndrome.", "Interstitial 6q25 microdeletion syndrome (ICS) is a rare autosomal dominant disorder characterized by loss-of-function mutations of the ARID1B gene and severe intrauterine and post-natal growth retardation", "The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14.", "Interstitial 6q25 microdeletion syndrome (IL-6q25) is a rare autosomal dominant disorder caused by mutations in the ARID1B gene, which encodes a major regulator of heme oxygenase 1 (HMOX1), resulting in a loss of a ubiquitously expressed protein, gigaxonin.", "Interstitial 6q25 microdeletion syndrome (IPS) is a rare autosomal dominant disorder characterized by loss-of-function mutations in the ARID1B gene, which encodes a major regulator of heme oxygenase 1 (HMOX1), and many other genes involved in heme catabolism.", "Interstitial 6q25 microdeletion syndrome (ICS) is a rare autosomal recessive genetic disorder characterized by loss-of-function mutations in the ARID1B gene, which encodes a major regulator of heme oxygenase activity." ], "exact_answer": [ "ARID1B" ], "type": "factoid", "id": "6031287e1cb411341a00012d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Interstitial 6q25 microdeletion syndrome: ARID1B is the key gene.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26754677", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1201, "text": "Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, these deletions are considered to be part of a unique microdeletion syndrome associated with intellectual disability and speech impairment, typical dysmorphic features, structural anomalies of the brain, microcephaly, and non-specific multiple organ anomalies. The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14. It has been hypothesized that haploinsufficiency of these genes impairs normal development of the brain and is responsible for the phenotype. This case report describes a girl presenting with typical features of 6q microdeletion syndrome, including global developmental delay, speech impairment, distinct dysmorphic features, dysgenesis of the corpus callosum, common limb anomalies, and hearing loss. Chromosome analysis by array-CGH revealed a small interstitial 6q deletion spanning approximately 1.1 Mb of DNA and containing only one coding gene, ARID1B. We suggest that ARID1B is the key gene behind 6q microdeletion syndrome, and we discuss its possible role in the phenotypic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26754677", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1201, "text": "We suggest that ARID1B is the key gene behind 6q microdeletion syndrome, and we discuss its possible role in the phenotypic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26754677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Interstitial 6q25 microdeletion syndrome: ARID1B is the key gene", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26754677", "endSection": "title" }, { "offsetInBeginSection": 344, "offsetInEndSection": 508, "text": "itical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14. It ha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26754677", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 502, "text": "The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26754677", "endSection": "abstract" } ] }, { "body": "Brensocatib was tested for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32897034" ], "ideal_answer": [ "Brensocatib was tested for bronchiectasis. Brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes." ], "exact_answer": [ "bronchiectasis" ], "type": "factoid", "id": "601c42ad1cb411341a00001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897034", "endSection": "title" }, { "offsetInBeginSection": 495, "offsetInEndSection": 789, "text": "METHODS: In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897034", "endSection": "abstract" }, { "offsetInBeginSection": 2176, "offsetInEndSection": 2380, "text": "CONCLUSIONS: In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897034", "endSection": "title" }, { "offsetInBeginSection": 2192, "offsetInEndSection": 2382, "text": "this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes. (F", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897034", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 768, "text": "cerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases.METHODS: In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib onc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897034", "endSection": "abstract" }, { "offsetInBeginSection": 1991, "offsetInEndSection": 2336, "text": "the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo.CONCLUSIONS: In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897034", "endSection": "abstract" } ] }, { "body": "What is the function of the protein Cuf1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11274192", "http://www.ncbi.nlm.nih.gov/pubmed/21489137", "http://www.ncbi.nlm.nih.gov/pubmed/18723604", "http://www.ncbi.nlm.nih.gov/pubmed/17384198", "http://www.ncbi.nlm.nih.gov/pubmed/12244050" ], "ideal_answer": [ "Cuf1 is a copper-sensing transcription factor." ], "exact_answer": [ "Cuf1 is a copper-sensing transcription factor." ], "type": "factoid", "id": "60355c0f1cb411341a000156", "snippets": [ { "offsetInBeginSection": 106, "offsetInEndSection": 213, "text": " CUF1 was involved both in copper acquisition and in copper detoxification in response to copper variation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21489137", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 990, "text": "the transcription factor Cuf1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18723604", "endSection": "abstract" }, { "offsetInBeginSection": 88, "offsetInEndSection": 114, "text": "transcription factor Cuf1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17384198", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 555, "text": " copper-sensing transcription factor Cuf1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12244050", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1046, "text": "copper-sensing transcription factor Cuf1, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11274192", "endSection": "abstract" } ] }, { "body": "How many groups of viruses exist in the Baltimore Classification?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28588308", "http://www.ncbi.nlm.nih.gov/pubmed/32132243" ], "ideal_answer": [ "There are seven \"Baltimore classes\" (BCs) that define the major features of virus reproduction.", "seven \"Baltimore classes\" (BCs) that define the major features of virus reproduction", "The Baltimore Classification system consists of seven classes (A, B, C, D, E, F, G, C and D) that are classified into seven different regions based on sequence similarity." ], "exact_answer": [ "7", "seven" ], "type": "factoid", "id": "601f10b71cb411341a000072", "snippets": [ { "offsetInBeginSection": 289, "offsetInEndSection": 374, "text": " seven \"Baltimore classes\" (BCs) that define the major features of virus reproduction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32132243", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 1002, "text": "Phylogenetic analyses of virus hallmark genes combined with analyses of gene-sharing networks show that replication modules of five BCs (three classes of RNA viruses and two classes of reverse-transcribing viruses) evolved from a common ancestor that encoded an RNA-directed RNA polymerase or a reverse transcriptase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32132243", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 375, "text": "Comparison of these routes led to the classification of viruses into seven \"Baltimore classes\" (BCs) that define the major features of virus reproduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32132243", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 378, "text": "Comparison of these routes led to the classification of viruses into seven \"Baltimore classes\" (BCs) that define the major features of virus reproduction. Ho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32132243", "endSection": "abstract" }, { "offsetInBeginSection": 1007, "offsetInEndSection": 1202, "text": "In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28588308", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 1001, "text": "Phylogenetic analyses of virus hallmark genes combined with analyses of gene-sharing networks show that replication modules of five BCs (three classes of RNA viruses and two classes of reverse-transcribing viruses) evolved from a common ancestor that encoded an RNA-directed RNA polymerase or a reverse transcriptase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32132243", "endSection": "abstract" } ] }, { "body": "What is the effect of Dkk1 in Wnt signaling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22363428", "http://www.ncbi.nlm.nih.gov/pubmed/14695408", "http://www.ncbi.nlm.nih.gov/pubmed/15378020", "http://www.ncbi.nlm.nih.gov/pubmed/29763912", "http://www.ncbi.nlm.nih.gov/pubmed/24671437", "http://www.ncbi.nlm.nih.gov/pubmed/20142103", "http://www.ncbi.nlm.nih.gov/pubmed/11044603", "http://www.ncbi.nlm.nih.gov/pubmed/14695885", "http://www.ncbi.nlm.nih.gov/pubmed/20161711", "http://www.ncbi.nlm.nih.gov/pubmed/21811562", "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "http://www.ncbi.nlm.nih.gov/pubmed/21861760", "http://www.ncbi.nlm.nih.gov/pubmed/17295608", "http://www.ncbi.nlm.nih.gov/pubmed/30216540", "http://www.ncbi.nlm.nih.gov/pubmed/28849121", "http://www.ncbi.nlm.nih.gov/pubmed/26880631", "http://www.ncbi.nlm.nih.gov/pubmed/20543981", "http://www.ncbi.nlm.nih.gov/pubmed/20618428", "http://www.ncbi.nlm.nih.gov/pubmed/29165387", "http://www.ncbi.nlm.nih.gov/pubmed/24520934", "http://www.ncbi.nlm.nih.gov/pubmed/23261660" ], "ideal_answer": [ "Transcriptional silencing of the Wnt-antagonist DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis.", "DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis.", "DKK1 is a secreted protein that inhibits WNT signaling and plays essential roles in vertebrate embryogenesis.", "DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis including head induction, skeletal development, and limb patterning." ], "type": "summary", "id": "5fdb41a2a43ad3127800001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Transcriptional silencing of the Wnt-antagonist DKK1 by promoter methylation is associated with enhanced Wnt signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22363428", "endSection": "title" }, { "offsetInBeginSection": 388, "offsetInEndSection": 562, "text": "DKK1 itself is a target of TCF/\u03b2-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22363428", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Continuous antagonism by Dkk1 counter activates canonical Wnt signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21861760", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Dkk1-dependent inhibition of Wnt signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24520934", "endSection": "title" }, { "offsetInBeginSection": 1168, "offsetInEndSection": 1214, "text": "Wnt inhibition caused by the AVE-derived Dkk1,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24520934", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 843, "text": "Wnt signal inhibitors, Dkk1 or XAV939", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24520934", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 30, "text": "DKK1 antagonizes Wnt signaling", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 867, "text": "One model suggests that DKK1 binding to LRP6 disrupts Wnt-induced Frizzled-LRP6 complex formation, whereas the other model proposes that DKK1 interaction with LRP6 promotes LRP6 internalization and degradation, thereby reducing the cell surface LRP6 level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "abstract" }, { "offsetInBeginSection": 1304, "offsetInEndSection": 1401, "text": " We conclude that DKK1 inhibition of LRP6 is independent of LRP6 internalization and degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "DKK1 mediated inhibition of Wnt signaling ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20161711", "endSection": "title" }, { "offsetInBeginSection": 839, "offsetInEndSection": 996, "text": "Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20161711", "endSection": "abstract" }, { "offsetInBeginSection": 1279, "offsetInEndSection": 1457, "text": "Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20161711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 36, "text": "Suppression of Wnt signaling by Dkk1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20142103", "endSection": "title" }, { "offsetInBeginSection": 95, "offsetInEndSection": 137, "text": "DKK1-mediated inhibition of Wnt signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17295608", "endSection": "title" }, { "offsetInBeginSection": 132, "offsetInEndSection": 310, "text": "n vitro studies suggest that a reduced antagonistic effect of DKK1 on canonical Wnt signaling contributes to the molecular effect of this mutation and its pathogenic consequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17295608", "endSection": "abstract" }, { "offsetInBeginSection": 958, "offsetInEndSection": 1083, "text": "Wnt signal activation in the absence and presence of DKK1 was assessed using a TCF4-based reporter gene assay in Saos-2 cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17295608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15378020", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "The role of the Wnt-signaling antagonist DKK1 in the development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14695408", "endSection": "title" }, { "offsetInBeginSection": 379, "offsetInEndSection": 482, "text": "We found that dkk1 blocks the post-MBT Wnt signaling and dkk1 is a target of the pre-MBT Wnt signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11044603", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 986, "text": "Our findings further demonstrated that miR-217 promoted the CSC-like phenotype via dickkopf-1\u00a0(DKK1) targeting, resulting in constitutive activation of Wnt signaling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28849121", "endSection": "abstract" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1518, "text": "Specifically, TNF\u03b1 triggered induction of the Wnt signaling inhibitor Dkk1 in the osteoblasts at the mRNA and protein levels, with a simultaneous increase in RANKL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30216540", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 299, "text": "Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the Frizzled-Wnt-LRP6 complex formation in response to Wnts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20543981", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1786, "text": "Forced overexpression of DKK1 antagonized the effects of GATA6 on Wnt signaling in pancreatic cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21811562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis including head induction, skeletal development, and limb patterning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 310, "text": "In vitro studies suggest that a reduced antagonistic effect of DKK1 on canonical Wnt signaling contributes to the molecular effect of this mutation and its pathogenic consequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17295608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "title" }, { "offsetInBeginSection": 401, "offsetInEndSection": 566, "text": "Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29763912", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 353, "text": "Dickkopf1 (DKK1) is known to antagonize Wnt signaling by direct high-affinity binding to the extracellular domain of WNT coreceptor lipoprotein receptor-related protein 6 (LRP6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20618428", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 567, "text": "f-related protein 1 (Dkk1), a vital antagonist of the Wnt signaling, was reported to be closely associated with bone homeostasis and osteoporosis. Interest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26880631", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 292, "text": "gnaling. Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the Frizzled-Wnt-LRP6 complex formation in response t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20543981", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1765, "text": "These results indicate the efficacy of systemic expression of secreted Wnt antagonists as a general strategy for conditional inactivation of Wnt signaling in adult organisms and illustrate a striking reliance on a single growth factor pathway for the maintenance of the architecture of the adult small intestine and colon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14695885", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 445, "text": "Along these lines, one mechanism through which E2 protects the hippocampus from cerebral ischemia is by preventing the post-ischemic elevation of Dkk1, a neurodegenerative factor that serves as an antagonist of the canonical Wnt signaling pathway, and simultaneously inducing pro-survival Wnt/\u03b2-Catenin signaling in hippocampal neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23261660", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 566, "text": "Specifically, we revealed a mechanism by which IL1\u03b2 upregulates WNT signaling via downregulating WNT antagonists, DKK1 and FRZB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29165387", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 500, "text": "DKK1 is a high affinity antagonistic ligand for LRP6, which is a Wnt coreceptor that acts together with the Frizzled serpentine receptor to initiate Wnt signal transduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 610, "text": "Two different models have been proposed to account for the mechanism by which DKK1 antagonizes LRP6 function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18505732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Bidirectional effect of Wnt signaling antagonist DKK1 on the modulation of anthrax toxin uptake.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24671437", "endSection": "title" } ] }, { "body": "What is bimagrumab", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27167138", "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "http://www.ncbi.nlm.nih.gov/pubmed/29226558", "http://www.ncbi.nlm.nih.gov/pubmed/29566437" ], "ideal_answer": [ "Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators." ], "type": "summary", "id": "602c1dc41cb411341a00011f", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 185, "text": "Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Bimagrumab (BYM338) is a novel fully human monoclonal antibody that exerts strong promyogenic effects on skeletal muscle by blocking activin type II receptors (ActRII).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27167138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "RATIONALE: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30095981", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "BACKGROUND: Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29566437", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 314, "text": "Bimagrumab is a human anti-ActRII antibody which was found to increase muscle mass and function by blocking ActRII signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29226558", "endSection": "abstract" } ] }, { "body": "List orally bioavailable MPS1 kinase inhibitors", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21159646", "http://www.ncbi.nlm.nih.gov/pubmed/29380674", "http://www.ncbi.nlm.nih.gov/pubmed/27335255", "http://www.ncbi.nlm.nih.gov/pubmed/28334731", "http://www.ncbi.nlm.nih.gov/pubmed/31575759" ], "ideal_answer": [ "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazalo,bos172722 and cct251455.", "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazolo, bos172722, cCT251455.", "MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in a wide range of human tumors and is necessary for tumoral cell proliferation. CCT251455, BOS172722, CCT271850, 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides and NMS-P715 are orally bioavailable MPS1 kinase inhibitors.", "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazolo, bos172722 and cct251455 are orally bioavailable MPS1 kinase inhibitors.", "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazola,bos172722 and cct251455 are orally bioavailable MPS1 kinase inhibitors." ], "exact_answer": [ [ "CCT251455" ], [ "BOS172722", "CCT289346" ], [ "CCT271850" ], [ "4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides" ], [ "NMS-P715" ] ], "type": "list", "id": "602a87c71cb411341a000117", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29380674", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31575759", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly checkpoint activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31575759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334731", "endSection": "title" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1741, "text": " CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24\u2009h is required to achieve tumour stasis or regression by CCT271850.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28334731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27335255", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159646", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 822, "text": "MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in a wide range of human tumors and is necessary for tumoral cell proliferation. Here we report the identification and characterization of NMS-P715, a selective and orally bioavailable MPS1 small-molecule inhibitor, which selectively reduces cancer cell proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates mitosis and affects kinetochore components localization causing massive aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor growth in preclinical cancer models. Inhibiting the SAC could represent a promising new approach to selectively target cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21159646", "endSection": "abstract" } ] }, { "body": "Can radiosurgery be used for the DNET tumors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28868186", "http://www.ncbi.nlm.nih.gov/pubmed/17240596" ], "ideal_answer": [ "Yes, radiosurgery is used for the DNET (Dysembryoplastic neuroepithelial) tumors. However, the level of evidence is limited." ], "exact_answer": "yes", "type": "yesno", "id": "601c44ab1cb411341a00001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Salvage gamma knife radiosurgery in the management of dysembryoplastic neuroepithelial tumors: Long-term outcome in a single-institution case series.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868186", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 372, "text": "BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNT/DNET) are rare epileptogenic tumors. Microsurgery remains the best treatment option, although case reports exist on the use of gamma knife radiosurgery (GKRS) in selected cases. We investigated the long-term outcome of GKRS-treated DNTs at our institution in the context of current diagnostic and treatment options.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868186", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 1512, "text": "Long-term seizure control was obtained after GKRS of two separate residual DNT components along the surgical margin (2005 and 2010). A 27-year-old male undergoing gross total resection of the contrast-enhancing portion of a DNT (1999) resulted in temporary control of intractable epilepsy despite AEDs; lasting clinical control of seizures was achieved in 2002 after GKRS of a small, recurrent DNT component. A 28-year-old male underwent STR of DNT (1994 and 2004) resulting in temporary control of intractable epilepsy. Lasting seizure control was gained after GKRS of a residual tumor (2005).CONCLUSION: GKRS as performed in our series was effective in terms of tumor and seizure control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868186", "endSection": "abstract" }, { "offsetInBeginSection": 1557, "offsetInEndSection": 1646, "text": "Prospective studies are warranted to establish the role of GKRS in the treatment of DNTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Two rare cases of intractable epilepsy caused by Dysembryoplastic Neuroepithelial Tumours (DNET) are reported and their different management discussed. The first case required vagal nerve stimulation and radiosurgery while the later was operated with the help of neuronavigation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17240596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Salvage gamma knife radiosurgery in the management of dysembryoplastic neuroepithelial tumors: Long-term outcome in a single-institution case series", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868186", "endSection": "title" } ] }, { "body": "What are commensal bacteria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30672882", "http://www.ncbi.nlm.nih.gov/pubmed/31049923", "http://www.ncbi.nlm.nih.gov/pubmed/33186243", "http://www.ncbi.nlm.nih.gov/pubmed/32758517" ], "ideal_answer": [ "The gut microbiota is composed of a large number of microbes, usually regarded as commensal bacteria. Maintenance of the commensal bacteria that comprise the gut microbiome is essential to both gut and systemic health." ], "type": "summary", "id": "6032866a1cb411341a000142", "snippets": [ { "offsetInBeginSection": 652, "offsetInEndSection": 791, "text": "Predominant bacteria vary, but overall, patients with vasculitis tend to have more pathogenic and less commensal bacteria in active disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The gut microbiota is composed of a large number of microbes, usually regarded as commensal bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32758517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Maintenance of the commensal bacteria that comprise the gut microbiome is essential to both gut and systemic health.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30672882", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 91, "text": "Commensal bacteria are a major factor in human health and disease pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31049923", "endSection": "abstract" } ] }, { "body": "What disease is associate with defects in both the KDM6A (lysine specific demethylase 6A) and KMT2D (lysine methyltransferase 2D)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31740281", "http://www.ncbi.nlm.nih.gov/pubmed/29073101", "http://www.ncbi.nlm.nih.gov/pubmed/31924266", "http://www.ncbi.nlm.nih.gov/pubmed/30509212", "http://www.ncbi.nlm.nih.gov/pubmed/24838796", "http://www.ncbi.nlm.nih.gov/pubmed/29725259", "http://www.ncbi.nlm.nih.gov/pubmed/31282990", "http://www.ncbi.nlm.nih.gov/pubmed/27028180", "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "http://www.ncbi.nlm.nih.gov/pubmed/25934606", "http://www.ncbi.nlm.nih.gov/pubmed/32817139", "http://www.ncbi.nlm.nih.gov/pubmed/31883305" ], "ideal_answer": [ "Over the last 20 years, mutations in five key COMPASS complex genes have been linked to three human congenital syndromes: Kabuki syndrome (type 1 [KMT2D] and 2 [KDM6A]", "Kabuki syndrome is a rare genetic disorder, caused by mutation in the KMT2D or KDM6A genes, which affects several organs in the majority of patients, among which are the eyes." ], "exact_answer": [ "Kabuki syndrome", "KS" ], "type": "factoid", "id": "601ec2d61cb411341a000062", "snippets": [ { "offsetInBeginSection": 678, "offsetInEndSection": 849, "text": " Over the last 20 years, mutations in five key COMPASS complex genes have been linked to three human congenital syndromes: Kabuki syndrome (type 1 [KMT2D] and 2 [KDM6A]), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31924266", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 318, "text": "Heterozygous, de novo dominant mutations in either KMT2D or KDM6A underlie KS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31883305", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 875, "text": "ll 25 patients with KS carried de novo, likely pathogenic or pathogenic variants in either KMT2D or KDM6A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31883305", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 175, "text": "abuki syndrome is a rare genetic disorder, caused by mutation in the KMT2D or KDM6A genes, which affects several organs in the majority of patients, among which are the eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31740281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Identification of KMT2D and KDM6A variants by targeted sequencing from patients with Kabuki syndrome and other congenital disorders", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "endSection": "title" }, { "offsetInBeginSection": 157, "offsetInEndSection": 333, "text": "Studies have determined that pathogenic variants of the lysine-specific methyltransferase 2D (KMT2D) and lysine-specific demethylase 6A (KDM6A) genes are the major causes of KS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "endSection": "abstract" }, { "offsetInBeginSection": 856, "offsetInEndSection": 1012, "text": "Overall, we uncovered 11 novel variants - nine in KMT2D and two in KDM6A. Seven of the novel variants (all KMT2D) were likely causative of the KS phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 270, "text": "Two genes have been shown to be mutated in patients with KS: lysine (K)-specific demethylase 6A (KDM6A) and lysine (K)-specific methyltransferase 2D (KMT2D, formerly MLL2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30509212", "endSection": "abstract" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1267, "text": "Finally, understanding the interactions between KMT2D and its target genes could unravel other candidate genes for hitherto unexplained Kabuki syndrome cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25934606", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 347, "text": "Kabuki syndrome is caused by mutations or deletions of lysine (K)-specific methyltransferase 2D (KMT2D) and lysine-specific methylase 6A (KDM6A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24838796", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 472, "text": "Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29725259", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 411, "text": "pite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29725259", "endSection": "abstract" }, { "offsetInBeginSection": 100, "offsetInEndSection": 224, "text": "Exonic deletions, disrupting the lysine (K)-specific demethylase 6A (KDM6A) gene have been demonstrated as rare cause of KS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27028180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Identification of KMT2D and KDM6A variants by targeted sequencing from patients with Kabuki syndrome and other congenital disorders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31935506", "endSection": "title" }, { "offsetInBeginSection": 164, "offsetInEndSection": 420, "text": "Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29725259", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 407, "text": "Heterozygous germline mutations in the KMT2D gene are known to cause Kabuki syndrome (OMIM 147920), a developmental multisystem disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31282990", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 740, "text": "Mutations of KDM6A cause Kabuki syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32817139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29073101", "endSection": "abstract" } ] }, { "body": "Which transcription factor regulates emergency granulopoiesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20581311", "http://www.ncbi.nlm.nih.gov/pubmed/19796237", "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "http://www.ncbi.nlm.nih.gov/pubmed/23382991", "http://www.ncbi.nlm.nih.gov/pubmed/25940801", "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "http://www.ncbi.nlm.nih.gov/pubmed/26267538", "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "http://www.ncbi.nlm.nih.gov/pubmed/16751774" ], "ideal_answer": [ "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in the differentiation and proliferation of hematopoietic stem cells.", "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPalpha is required are unknown . 'Steady-state' granulopsis is absolutely dependent on the C/ EBPalpha transcription factor .", "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in the differentiation and proliferation of hematopoietic stem cells. It is a transcription factor required for emergency granulopoiesis.", "Differentiation and proliferation of hematopoietic stem cells are regulated by C/EBP\u03b2, a transcription factor required for emergency granulopoiesis. Granulopoiesis during emergency situations, such as infection, is dependent on C/EBP\u03b2.", "These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.", "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in the differentiation and proliferation of hematopoietic stem cells. There is no definitive role of the transcription factor in emergency granulopoiesis.", "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) regulates the differentiation and proliferation of hematopoietic stem cells." ], "exact_answer": [ "c/EBP\u03b2", "c/EBPbeta" ], "type": "factoid", "id": "5fdb43aea43ad3127800002b", "snippets": [ { "offsetInBeginSection": 989, "offsetInEndSection": 1305, "text": "In this study, we observed that Stat3 and C/ebp\u03b2 activate FANCC transcription and contribute to DNA repair. Our findings indicate that FancC expression is increased during Stat3- and C/ebp\u03b2-induced initiation of emergency granulopoiesis by these transcription factors and is maintained through termination by Icsbp. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 149, "text": "Differentiation and proliferation of hematopoietic stem cells are regulated by C/EBP\u03b2, a transcription factor required for emergency granulopoiesis]", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "title" }, { "offsetInBeginSection": 340, "offsetInEndSection": 443, "text": "We previously showed that C/EBP\u03b2, which is a transcription factor required for emergency granulopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Cyclic AMP responsive element binding proteins are involved in 'emergency' granulopoiesis through the upregulation of CCAAT/enhancer binding protein \u03b2", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382991", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein \u03b1 (C/EBP\u03b1), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBP\u03b2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382991", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1162, "text": "Retroviral transduction of a dominant negative CREB mutant reduced C/EBP\u03b2 mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBP\u03b2 transcription", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382991", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1275, "text": "These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBP\u03b2 upregulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "C/EBP\u03b2 is involved in the amplification of early granulocyte precursors during candidemia-induced \"emergency\" granulopoiesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "title" }, { "offsetInBeginSection": 132, "offsetInEndSection": 247, "text": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in emergency granulopoiesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 922, "text": "Upon infection, C/EBP\u03b2 was upregulated at the protein level in all the granulopoietic subpopulations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 1165, "offsetInEndSection": 1337, "text": "aken together, these data suggest that C/EBP\u03b2 is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "C/EBPbeta is required for 'emergency' granulopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "title" }, { "offsetInBeginSection": 312, "offsetInEndSection": 447, "text": "Here we show that large numbers of granulocytes were generated from C/EBPalpha-deficient progenitors after cytokine stimulation in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 935, "text": "These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 542, "text": "We previously showed that C/EBP\u03b2, which is a transcription factor required for emergency granulopoiesis, plays a pivotal role at the level of hematopoietic stem/progenitor cells under stress conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "[Differentiation and proliferation of hematopoietic stem cells are regulated by C/EBP\u03b2, a transcription factor required for emergency granulopoiesis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "title" }, { "offsetInBeginSection": 132, "offsetInEndSection": 326, "text": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBP\u03b2 is required are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein \u03b1 (C/EBP\u03b1), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBP\u03b2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382991", "endSection": "abstract" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1337, "text": "Taken together, these data suggest that C/EBP\u03b2 is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 311, "text": "'Steady-state' granulopoiesis is absolutely dependent on the C/EBPalpha transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Stat3 and CCAAT enhancer-binding protein \u03b2 (C/ebp\u03b2) activate Fanconi C gene transcription during emergency granulopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "endSection": "title" }, { "offsetInBeginSection": 2, "offsetInEndSection": 150, "text": "ifferentiation and proliferation of hematopoietic stem cells are regulated by C/EBP\u03b2, a transcription factor required for emergency granulopoiesis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein \u03b1 (C/EBP\u03b1), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBP\u03b2. In t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382991", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 334, "text": "anscription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBP\u03b2 is required are unknown. In this", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024276", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 549, "text": "viously showed that C/EBP\u03b2, which is a transcription factor required for emergency granulopoiesis, plays a pivotal role at the level of hematopoietic stem/progenitor cells under stress conditions. Upon e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 315, "text": "dy-state' granulopoiesis is absolutely dependent on the C/EBPalpha transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear. Her", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1093, "text": " controls G-CSF-dependent expression of CCAAT-enhancer-binding protein \u03b2 (C/EBP\u03b2), a crucial factor in the emergency granulopoiesis response. Moreover, STAT", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581311", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 460, "text": "ranulocyte production increases following infection or in response to cytokine stimulation, and activation of the CCAAT/enhancer-binding protein \u03b2 (C/EBP\u03b2) transcription factor is required for such stress-induced granulopoiesis, whereas C/EBP\u03b1 plays a critical role in maintaining steady-state granulopoiesis. Dif", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25940801", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1296, "text": "epair. Our findings indicate that FancC expression is increased during Stat3- and C/ebp\u03b2-induced initiation of emergency granulopoiesis by these transcription factors and is maintained through termination b", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "endSection": "abstract" }, { "offsetInBeginSection": 1759, "offsetInEndSection": 2007, "text": "Since CN patients respond to G-CSF treatment even in the absence of LEF-1 and C/EBPalpha, we conclude that treatment of CN patients with pharmacological doses of G-CSF activates NAMPT/NAD(+)/SIRT1-dependent \"emergency\" granulopoiesis via C/EBPbeta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19796237", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 413, "text": "Icsbp inhibits the expression of Stat3 and C/ebp\u03b2, transcription factors essential for initiating and sustaining granulopoiesis, and activates transcription of Fanconi C (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 625, "text": "RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBP\u03b2) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26267538", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1078, "text": "STAT3 directly controls G-CSF-dependent expression of CCAAT-enhancer-binding protein \u03b2 (C/EBP\u03b2), a crucial factor in the emergency granulopoiesis response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20581311", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 311, "text": "Steady-state' granulopoiesis is absolutely dependent on the C/EBPalpha transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 704, "text": "Cytokine treatment or fungal infection induced upregulation of C/EBPbeta but not C/EBPalpha or C/EBPepsilon transcripts in granulocyte progenitors, and C/EBPbeta-deficient progenitors showed decreased emergency-induced granulopoiesis in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 448, "text": "Here we show that large numbers of granulocytes were generated from C/EBPalpha-deficient progenitors after cytokine stimulation in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 773, "text": "C/EBPbeta inhibited proliferation less severely than did C/EBPalpha.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751774", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 966, "text": "Further elucidation of the functions and regulation of C/EBP\u03b2 in hematopoietic stem cells will facilitate an understanding of stress hematopoiesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973462", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1304, "text": "Our findings indicate that FancC expression is increased during Stat3- and C/ebp\u03b2-induced initiation of emergency granulopoiesis by these transcription factors and is maintained through termination by Icsbp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29382715", "endSection": "abstract" } ] }, { "body": "When did eptinezumab get its first FDA approval?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32266704" ], "ideal_answer": [ "In February 2020, eptinezumab was approved in the USA for the preventive treatment of migraine in adults." ], "exact_answer": [ "In February 2020" ], "type": "factoid", "id": "6026ef9d1cb411341a0000d5", "snippets": [ { "offsetInBeginSection": 415, "offsetInEndSection": 521, "text": " In February 2020, eptinezumab was approved in the USA for the preventive treatment of migraine in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32266704", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 521, "text": "In February 2020, eptinezumab was approved in the USA for the preventive treatment of migraine in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32266704", "endSection": "abstract" } ] }, { "body": "Which database exists that contains regulatory sites for splicing in human basal ganglia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32098967" ], "ideal_answer": [ "Braineacv2 has been identified as a database that contains regulatory sites for splicing in human basal ganglia.", "Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. Disease-relevant regulatory loci were identified, finding that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through http://braineacv2.inf.um.es/.", "Braineacv2 is a database that contains regulatory sites for splicing in human basal ganglia." ], "exact_answer": [ "http://braineacv2.inf.um.es/" ], "type": "factoid", "id": "6030fcb51cb411341a000127", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32098967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1163, "text": "Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web\u00a0server, http://braineacv2.inf.um.es/.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32098967", "endSection": "abstract" } ] }, { "body": "Should minocycline be used for mild Alzheimer disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31738372" ], "ideal_answer": [ "No. Minocycline did not delay the progress of cognitive or functional impairment in people with mild Alzheimer disease during a 2-year period." ], "exact_answer": "no", "type": "yesno", "id": "6026754f1cb411341a0000c8", "snippets": [ { "offsetInBeginSection": 3015, "offsetInEndSection": 3166, "text": "Conclusions and Relevance: Minocycline did not delay the progress of cognitive or functional impairment in people with mild AD during a 2-year period. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31738372", "endSection": "abstract" } ] }, { "body": "What is pyroptosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30917630", "http://www.ncbi.nlm.nih.gov/pubmed/31733200", "http://www.ncbi.nlm.nih.gov/pubmed/31710896", "http://www.ncbi.nlm.nih.gov/pubmed/31756255" ], "ideal_answer": [ "Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1\u03b2. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules." ], "type": "summary", "id": "60490a0f1cb411341a000165", "snippets": [ { "offsetInBeginSection": 245, "offsetInEndSection": 493, "text": " Apoptosis is recognized relatively easily due to its unique morphology, but lytic cell death may occur in the form of accidental necrosis, mitochondria permeability transition-driven necrosis, necroptosis, pyroptosis, ferroptosis, and parthanatos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917630", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Pyroptosis is a pro-inflammatory form of programmed cell death, whose genesis directly depended on caspase-1 activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31733200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Pyroptosis is a type of programmed lytic cell death that could be activated by either the canonical or noncanonical inflammasome pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31756255", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 482, "text": "Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1\u03b2. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31710896", "endSection": "abstract" } ] }, { "body": "What is a HapMap", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16877472", "http://www.ncbi.nlm.nih.gov/pubmed/21210977", "http://www.ncbi.nlm.nih.gov/pubmed/16982009", "http://www.ncbi.nlm.nih.gov/pubmed/18453083", "http://www.ncbi.nlm.nih.gov/pubmed/19933162", "http://www.ncbi.nlm.nih.gov/pubmed/22844100", "http://www.ncbi.nlm.nih.gov/pubmed/17943122", "http://www.ncbi.nlm.nih.gov/pubmed/12615007", "http://www.ncbi.nlm.nih.gov/pubmed/20869033", "http://www.ncbi.nlm.nih.gov/pubmed/19913122", "http://www.ncbi.nlm.nih.gov/pubmed/17568388", "http://www.ncbi.nlm.nih.gov/pubmed/16434598", "http://www.ncbi.nlm.nih.gov/pubmed/16374835", "http://www.ncbi.nlm.nih.gov/pubmed/17033966", "http://www.ncbi.nlm.nih.gov/pubmed/21356867", "http://www.ncbi.nlm.nih.gov/pubmed/14685227", "http://www.ncbi.nlm.nih.gov/pubmed/19286890", "http://www.ncbi.nlm.nih.gov/pubmed/15454560", "http://www.ncbi.nlm.nih.gov/pubmed/17922574", "http://www.ncbi.nlm.nih.gov/pubmed/22319179", "http://www.ncbi.nlm.nih.gov/pubmed/15587301" ], "ideal_answer": [ "HapMap is a international effort for creating an annotated haplotype map of the world\u2019s most commonhaplotype sequences.", "HapMap provides linkage disequilibrium information on a sample of 3.7 million SNPs that can be used for tag SNP selection in whole-genome association studies.", "A haplotype map (HapMap)is aimed at describing these variation patterns across the entire genome and has been recently developed by the International HapMap Consortium. HapMap characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed.", "The \"HapMap\" project is now underway to characterize patterns of LD in the human genome.", "The HapMap haplotype map project aims to systematically map all human haplotypes, chromosome by chromosome, in a gene-dependent manner through dedicated efforts from national and international teams.", "The HapMap haplotype map project aims to systematically map all human haplotypes, chromosome by chromosome, in a gene-rich manner through dedicated efforts from national and international teams.", "The International Haplotype Map Project (HapMap) is an international effort for creating an annotated haplotype map of the human genome using protein sequences and other genomic data.", "A HapMap is a map of the human genome. It's a 3.1 million human single nucleotide polymorphisms (SNPs) that can be genotyped and mapped." ], "exact_answer": [ "a haplotype map of the human genome", "The \"HapMap\" project is now underway to characterize patterns of LD in the human genome", "Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms" ], "type": "factoid", "id": "601db8111cb411341a00004b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17943122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "The International Haplotype Map Project (HapMap) has provided an essential database for studies of human population genetics and genome-wide association. Phases I and II of the HapMap project generated genotype data across \u223c3 million SNP loci in 270 individuals representing four populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20869033", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 316, "text": ". A haplotype map (HapMap), aimed at describing these variation patterns across the entire genome, has been recently developed by the International HapMap Consortium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15454560", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 891, "text": ". We discuss in the same context the haplotype map project (HapMap) as a tool to facilitate the study of possible associations of genome changes and common diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15587301", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 233, "text": "The \"HapMap\" project is now underway to characterize patterns of LD in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12615007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "One of the goals of the International HapMap Project is the identification of common haplotypes in genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16434598", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 355, "text": "One of the particular important projects is The International HapMap Project which provides the catalogue of human genetic variation for disease association studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982009", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 475, "text": "A key goal of the HapMap Project is to enable identification of tag single nucleotide polymorphisms (SNPs) that capture a substantial portion of common human genetic variability while requiring only a small fraction of SNPs to be genotyped [International HapMap Consortium, 2005: Nature 437:1299-1320].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16374835", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 374, "text": "The International HapMap Consortium undertook an effort to catalog all common variation across the genome (variants with a minor allele frequency (MAF) of at least 5% in one or more ethnic groups).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22319179", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 880, "text": "al genome collaborations, such as HapMap and the Welcome Trust Case-Control Consortium single nucleotide polymorphism (SNP) mapping project have identified common genetic variations in diseases of major public health importance. Such genetic s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19286890", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 839, "text": "To facilitate evaluation of existing evidence of association and further work, we supplemented the extensive genotype data, available through the International HapMap Project (HapMap), about DTNBP1 by specifically typing all associated single-nucleotide polymorphisms reported in each of the studies of the Centre d'Etude du Polymorphisme Humain (CEPH)-derived HapMap sample (CEU).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17033966", "endSection": "abstract" }, { "offsetInBeginSection": 609, "offsetInEndSection": 864, "text": "In this chapter, we will demonstrate how to use the HapMap resource and the Haploview program to process and analyze genetic data from HapMap, to evaluate LD relations between SNPs, and to select tagging SNPs to be examined in disease association studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18453083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "With the availability of the HapMap--a resource which describes common patterns of linkage disequilibrium (LD) in four different human population samples, we now have a powerful tool to help dissect the role of genetic variation in the biology of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16877472", "endSection": "abstract" }, { "offsetInBeginSection": 1386, "offsetInEndSection": 1637, "text": "Although our SNP selection was based on HapMap data, which is a subset of all common SNPs, these panels effectively capture the majority of all common variation and provide high power to detect risk alleles that are not represented in the HapMap data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17922574", "endSection": "abstract" }, { "offsetInBeginSection": 1111, "offsetInEndSection": 1473, "text": "Our results demonstrate that the HapMap CEU samples provide an adequate basis for tag SNP selection in Finnish individuals, without the need to create a map specifically for the Finnish population, and suggest that the four-population HapMap data will provide useful information for tag SNP selection beyond the specific populations from which they were sampled.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16374835", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 1282, "text": "RESULTS: For each SNP, the SCAN database provides: (i) summary information from eQTL mapping of HapMap SNPs to gene expression (evaluated by the Affymetrix exon array) in the full set of HapMap CEU (Caucasians from UT, USA) and YRI (Yoruba people from Ibadan, Nigeria) samples; (ii) LD information, in the case of a HapMap SNP, including what genes have variation in strong LD (pairwise or multilocus LD) with the variant and how well the SNP is covered by different high-throughput platforms; (iii) summary information available from public databases (e.g.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933162", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 563, "text": "The HapMap project is one of the largest public resources of human single-nucleotide polymorphisms (SNPs), characterizing over 3 million SNPs genotyped in over 1000 individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22844100", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 685, "text": "Then, we study how well the HapMap SNPs capture the untyped SNPs in the region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16982009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "HapMap provides linkage disequilibrium (LD) information on a sample of 3.7 million SNPs that can be used for tag SNP selection in whole-genome association studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17568388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "INTRODUCTIONThe primary goal of the International Haplotype Map Project has been to develop a haplotype map of the human genome that describes the common patterns of genetic variation, in order to accelerate the search for the genetic causes of human disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21356867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "BACKGROUND: The HapMap project is a publicly available catalogue of common genetic variants that occur in humans, currently including several million SNPs across 1115 individuals spanning 11 different ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21210977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14685227", "endSection": "abstract" } ] }, { "body": "Which cancer types are associated with mutations in the TWIST1 gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24117170", "http://www.ncbi.nlm.nih.gov/pubmed/21330172", "http://www.ncbi.nlm.nih.gov/pubmed/21876555", "http://www.ncbi.nlm.nih.gov/pubmed/30272327", "http://www.ncbi.nlm.nih.gov/pubmed/29123266", "http://www.ncbi.nlm.nih.gov/pubmed/29455655", "http://www.ncbi.nlm.nih.gov/pubmed/25368021", "http://www.ncbi.nlm.nih.gov/pubmed/25622896", "http://www.ncbi.nlm.nih.gov/pubmed/25892968", "http://www.ncbi.nlm.nih.gov/pubmed/28851812", "http://www.ncbi.nlm.nih.gov/pubmed/28466252", "http://www.ncbi.nlm.nih.gov/pubmed/23623921", "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "http://www.ncbi.nlm.nih.gov/pubmed/21502402", "http://www.ncbi.nlm.nih.gov/pubmed/29477381", "http://www.ncbi.nlm.nih.gov/pubmed/19373776", "http://www.ncbi.nlm.nih.gov/pubmed/30265861", "http://www.ncbi.nlm.nih.gov/pubmed/29452232", "http://www.ncbi.nlm.nih.gov/pubmed/23364532", "http://www.ncbi.nlm.nih.gov/pubmed/20689556", "http://www.ncbi.nlm.nih.gov/pubmed/27524420", "http://www.ncbi.nlm.nih.gov/pubmed/19863427" ], "ideal_answer": [ "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1, are observed in ~\\n10% of all human cancers, including gastric, non-small cell lung, breast ductal carcinoma, nonsmall cell lung cancer, prostate cancer, ovarian cancer, breast tumor, papillary thyroid cancer, and gastric cancer.", "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, lung cancer, and skin cancer.", "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, lung cancer, and lung cancer.", "TWIST1, an epithelial-mesenchymal transition (EMT) transcription factor, is critical for oncogene-driven non-small cell lung cancer (NSCLC) tumorigenesis. STAT3 mediates TGF-\u03b21-induced TWIST1 expression and prostate cancer invasion. Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. The Transcription Factor ETV5 Mediates BRAFV600E-Induced Proliferation and TWIST1 Expression in Papillary Thyroid Cancer Cells.", "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, and lung cancer.", "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, lung cancer, and prostate cancer.", "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1 (PRC1), are observed in ~\\n10% of patients with gastric, non-small cell lung, breast ductal carcinomas, nonsmall cell lung cancer, prostate cancer, ovarian cancer, breast tumor, papillary thyroid cancer, and gastric cancer.", "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1 (PRC1), are observed in ~\\n10% of patients with gastric, non-small cell lung, breast ductal carcinomas, nonsmall cell lung cancer, prostate cancer, female breast cancer, ovarian cancer, breast tumor, papillary thyroid cancer, and gastric cancer.", "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1 (PRC1), are observed in ~\\n10% of patients with gastric, non-small cell lung, breast ductal carcinomas, nonsmall cell lung cancer, prostate cancer, ovarian cancer, breast tumor, papillary thyroid cancer, cervical cancer, adenoid cystic carcinoma, salivary gland neoplasms." ], "exact_answer": [ [ "prostate cancer" ], [ "breast cancer" ], [ "lung cancer" ], [ "thyroid cancer" ] ], "type": "list", "id": "5fda3dcaa43ad31278000006", "snippets": [ { "offsetInBeginSection": 377, "offsetInEndSection": 685, "text": "Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863427", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 456, "text": "Because of the potential importance of this finding, we organized a multicenter study enrolling people with TWIST1 mutation confirmed SCS to determine if an increased risk of cancer is present. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19373776", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 639, "text": "This Ser 68 is phosphorylated by p38, c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases1/2 in vitro, and its phosphorylation levels positively correlate with Twist1 protein levels in human embryonic kidney 293 and breast cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21502402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "STAT3 mediates TGF-\u03b21-induced TWIST1 expression and prostate cancer invasion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23623921", "endSection": "title" }, { "offsetInBeginSection": 137, "offsetInEndSection": 283, "text": "n the present study, we determined the underlying mechanisms of TGF-\u03b21-induced TWIST1 expression and its effect on prostate cancer cell invasion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23623921", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 927, "text": "we demonstrate a mechanistic cascade of TGF-\u03b21 up-regulating STAT3 activation and HIF-1\u03b1 stabilization and subsequent TWIST1 expression, leading to prostate cancer invasion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23623921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Differential expression and activation of epidermal growth factor receptor 1 (EGFR1), ERK, AKT, STAT3, and TWIST1 in nonsmall cell lung cancer (NSCLC).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24117170", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Inhibition of TWIST1 leads to activation of oncogene-induced senescence in oncogene-driven non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23364532", "endSection": "title" }, { "offsetInBeginSection": 1579, "offsetInEndSection": 1689, "text": "silencing of TWIST1 in oncogene driver-dependent NSCLCs represents a novel and promising therapeutic strategy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23364532", "endSection": "abstract" }, { "offsetInBeginSection": 765, "offsetInEndSection": 961, "text": "Silencing of TWIST1 in KRAS-mutant human NSCLC cell lines resulted in dramatic growth inhibition and either activation of a latent oncogene-induced senescence program or, in some cases, apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23364532", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 679, "text": "the basic helix-loop-helix transcription factor Twist1 cooperates with mutant Kras to induce lung adenocarcinoma in transgenic mouse models and that inhibition of Twist1 in these models led to Kras-induced senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23364532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25622896", "endSection": "title" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1838, "text": "Lastly, the dual phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor BEZ235 strongly attenuated TWIST1-induced migration that was dependent on the TQS motif. TWIST1 TQS phosphorylation state determines the intensity of TWIST1-induced pro-metastatic ability in prostate cancer cells, which may be partly explained mechanistically by TWIST1 dimeric partner choice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25622896", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 1043, "text": "The hypo-phosphorylation mimic Twist1-AQA mutation displayed reduced pro-metastatic activity compared to wild-type TWIST1 in vitro, suggesting that phosphorylation of the TWIST1 TQS motif was necessary for pro-metastatic functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25622896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Twist1 is a key regulator of cancer-associated fibroblasts", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25368021", "endSection": "title" }, { "offsetInBeginSection": 770, "offsetInEndSection": 918, "text": "In xenograft models, tumor infiltration of Twist1-expressing CAFs was enhanced strongly by ectopic IL6 expression in gastric or breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25368021", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1187, "text": "Enforced expression of Twist1 in normal fibroblasts was also sufficient to drive CAF marker expression and malignant character in gastric cancer cells both in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25368021", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "TWIST1, an epithelial-mesenchymal transition (EMT) transcription factor, is critical for oncogene-driven non-small cell lung cancer (NSCLC) tumorigenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28851812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The Transcription Factor ETV5 Mediates BRAFV600E-Induced Proliferation and TWIST1 Expression in Papillary Thyroid Cancer Cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30265861", "endSection": "title" }, { "offsetInBeginSection": 44, "offsetInEndSection": 170, "text": "up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477381", "endSection": "title" }, { "offsetInBeginSection": 1024, "offsetInEndSection": 1205, "text": "Combination of Twist1 siRNA and crizotinib significantly reduced cell vitality, inhibited cell invasion and migration, and promoted apoptosis in A549-CD74-ROS1 G2032R mutation cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477381", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1511, "text": "hese results suggested that CD74-ROS1 G2032R mutation mediated EMT phenotype by increasing the expression of Twist1, resulting in drug resistance. Combination of Twist1 silence and ROS1 inhibitor may provide a potent strategy to treat the ROS1+ NSCLC patients with crizotinib resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29477381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Disruption of ETV6 leads to TWIST1-dependent progression and resistance to epidermal growth factor receptor tyrosine kinase inhibitors in prostate cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29455655", "endSection": "title" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1506, "text": "Our results implicate ETV6 as a potential marker for predicting efficacy of an EGFR-targeted anticancer approach. Combination treatment of TWIST1 inhibitors could sensitize the anti-proliferation effects of EGFR-TKIs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29455655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Long noncoding RNA PVT1 promotes EMT via mediating microRNA-186 targeting of Twist1 in prostate cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452232", "endSection": "title" }, { "offsetInBeginSection": 669, "offsetInEndSection": 888, "text": "Furthermore, PVT1 can promote EMT by up-regulation of Twist1, a transcription factor associated with EMT. We then confirmed that PVT1 acts as a sponge for miRNA-186-5p and positively regulates Twist1 by a sponge effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452232", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1257, "text": "Mechanistically, Sox5 could bind to Twist1 promoter and active Twist1, which initiated EMT. Importantly, knockdown of Sox5 in prostate cancer cells resulted in less of the mesenchymal phenotype and cell migration ability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29123266", "endSection": "abstract" }, { "offsetInBeginSection": 1586, "offsetInEndSection": 1688, "text": "we propose a new mechanism in which Smad3/Sox5/Twist1 promotes EMT and contributes to PCa progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29123266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "TMPRSS4 Upregulates TWIST1 Expression through STAT3 Activation to Induce Prostate Cancer Cell Migration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28466252", "endSection": "title" }, { "offsetInBeginSection": 854, "offsetInEndSection": 1020, "text": "Taken together, we demonstrated a mechanistic cascade of TMPRSS4 up-regulating STAT3 activation and subsequent TWIST1 expression, leading to prostate cancer migration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28466252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21502402", "endSection": "title" }, { "offsetInBeginSection": 716, "offsetInEndSection": 888, "text": "Twist1 is expressed in breast, liver, prostate, gastric and other types of cancers, and its expression is usually associated with invasive and metastatic cancer phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21876555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863427", "endSection": "title" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1442, "text": "Tethered TWIST1-E12 heterodimers phenocopied the Twist1-DQD mutation for many in vitro assays, suggesting that TWIST1 phosphorylation may result in heterodimerization in prostate cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25622896", "endSection": "abstract" }, { "offsetInBeginSection": 1326, "offsetInEndSection": 1422, "text": "Our results also indicate that the TWIST1 gene may be a novel breast cancer susceptibility gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25622896", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "In humans, a germline mutation (c.309C>G) in the TWIST1 oncogene may predispose to breast cancer and its expression has been associated with tumour progression and metastasis. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863427", "endSection": "title" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1446, "text": " that the TWIST1 gene may be a novel breast cancer susceptibility gene. Additional studies are,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 435, "text": "Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27524420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Associations of gene\u2011wide SNPs in SNAI1 and TWIST1 with breast cancer and ovarian cancer susceptibility among Chinese Han women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30272327", "endSection": "title" }, { "offsetInBeginSection": 1636, "offsetInEndSection": 1943, "text": "These results indicate that tamoxifen can significantly accelerate Twist1 degradation to suppress cancer cell invasion and metastasis, suggesting that tamoxifen can be used not only to treat ER-positive breast cancers but also to reduce Twist1-mediated invasion and metastasis in ER-negative breast cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25892968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "In humans, a germline mutation (c.309C>G) in the TWIST1 oncogene may predispose to breast cancer and its expression has been associated with tumour progression and metastasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330172", "endSection": "abstract" }, { "offsetInBeginSection": 960, "offsetInEndSection": 1158, "text": "Twist1 levels were also elevated in metastatic prostate cancer-derived cell line DU145, in immortalized lung fibroblasts and in a subset of lung cancer samples, all in a mutant p53-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20689556", "endSection": "abstract" } ] }, { "body": "What did the RESILIENT study investigate?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31761834" ], "ideal_answer": [ "A global, randomized, double-blind placebo-controlled study was conducted to confirm that BYM338 (bimagrumab), an anti-activin type II receptor antibody, improves motor function in patients with sporadic inclusion body myositis after 52 weeks' treatment consisting of intravenous administration every 4 weeks at doses of 10, 3, and 1\u2005mg/kg." ], "type": "summary", "id": "602c1c701cb411341a00011d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "A global, randomized, double-blind placebo-controlled study was conducted to confirm that BYM338 (bimagrumab), an anti-activin type II receptor antibody, improves motor function in patients with sporadic inclusion body myositis after 52 weeks' treatment consisting of intravenous administration every 4 weeks at doses of 10, 3, and 1\u2005mg/kg. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31761834", "endSection": "abstract" } ] }, { "body": "List features of the Thrombotic Thrombocytopenic Purpura pentad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16104532", "http://www.ncbi.nlm.nih.gov/pubmed/1605172", "http://www.ncbi.nlm.nih.gov/pubmed/21415981", "http://www.ncbi.nlm.nih.gov/pubmed/23263974", "http://www.ncbi.nlm.nih.gov/pubmed/2647685", "http://www.ncbi.nlm.nih.gov/pubmed/18097325", "http://www.ncbi.nlm.nih.gov/pubmed/23767207", "http://www.ncbi.nlm.nih.gov/pubmed/11399382", "http://www.ncbi.nlm.nih.gov/pubmed/32190437", "http://www.ncbi.nlm.nih.gov/pubmed/23738162", "http://www.ncbi.nlm.nih.gov/pubmed/22233953", "http://www.ncbi.nlm.nih.gov/pubmed/21850657", "http://www.ncbi.nlm.nih.gov/pubmed/30447150", "http://www.ncbi.nlm.nih.gov/pubmed/32699732", "http://www.ncbi.nlm.nih.gov/pubmed/16616715", "http://www.ncbi.nlm.nih.gov/pubmed/29123569", "http://www.ncbi.nlm.nih.gov/pubmed/12423834", "http://www.ncbi.nlm.nih.gov/pubmed/9360410", "http://www.ncbi.nlm.nih.gov/pubmed/29270999", "http://www.ncbi.nlm.nih.gov/pubmed/1821908", "http://www.ncbi.nlm.nih.gov/pubmed/25512716", "http://www.ncbi.nlm.nih.gov/pubmed/22574558", "http://www.ncbi.nlm.nih.gov/pubmed/1171419", "http://www.ncbi.nlm.nih.gov/pubmed/10775033", "http://www.ncbi.nlm.nih.gov/pubmed/8427289", "http://www.ncbi.nlm.nih.gov/pubmed/16913442", "http://www.ncbi.nlm.nih.gov/pubmed/7863389", "http://www.ncbi.nlm.nih.gov/pubmed/12745043", "http://www.ncbi.nlm.nih.gov/pubmed/26634125", "http://www.ncbi.nlm.nih.gov/pubmed/17525362", "http://www.ncbi.nlm.nih.gov/pubmed/29340125", "http://www.ncbi.nlm.nih.gov/pubmed/19665681", "http://www.ncbi.nlm.nih.gov/pubmed/33024522", "http://www.ncbi.nlm.nih.gov/pubmed/30072561", "http://www.ncbi.nlm.nih.gov/pubmed/4038757", "http://www.ncbi.nlm.nih.gov/pubmed/12753286", "http://www.ncbi.nlm.nih.gov/pubmed/10541941", "http://www.ncbi.nlm.nih.gov/pubmed/12938786" ], "ideal_answer": [ "Thrombotic thrombocytopenic purpura (TTP) is typically characterized by the symptomatic pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, and renal failure." ], "exact_answer": [ [ "fever" ], [ "thrombocytopenia" ], [ "microangiopathic hemolytic anemia" ], [ "neurologic abnormalities" ], [ "renal failure" ] ], "type": "list", "id": "60274aca1cb411341a0000e3", "snippets": [ { "offsetInBeginSection": 147, "offsetInEndSection": 291, "text": "Our patient presented with the classic pentad of TTP symptoms: anemia, thrombocytopenia, fever, elevated creatinine, and altered mental status. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32190437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Thrombotic thrombocytopenic purpura (TTP) is typically characterized by the symptomatic pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, and renal failure.\u00a0", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32699732", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 584, "text": "Nonetheless, the classical pentad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurological dysfunction, kidney dysfunction and fever are seen only in 40 percent of the patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33024522", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 458, "text": "TTP has been characterized by the classical pentad of thrombocytopenia, hemolysis, fever, renal injury and neurological deficits, yet the patient may present with any atypical symptom related to microthrombi formation in the microcirculation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30447150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening illness with disseminated platelet-rich thromboses of small vessels that variably presents with the classic clinical \"pentad\" of microangiopathic hemolytic anemia, thrombocytopenia, fever, altered mental status, and acute kidney injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29270999", "endSection": "abstract" }, { "offsetInBeginSection": 509, "offsetInEndSection": 775, "text": "Thrombotic thrombocytopenic purpura (TTP) is a distinct, rare but potentially life-threatening entity that classically but not invariably presents with a pentad of acute onset haemolytic anaemia, thrombocytopenia, neurological symptoms, renal impairment and fevers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30072561", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 627, "text": "The patient was diagnosed thrombotic thrombocytopenic purpura (TTP) following pentad of clinical features: microangiopathic hemolytic anemia, thrombocytopenia, fever neurologic, and renal abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22574558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Thrombotic thrombocytopenic purpura (TTP) is a disorder of blood coagulation that presents classically with the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction and mental status changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Thrombotic thrombocytopenic purpura (TTP) is characterized by the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic symptoms, and renal dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1605172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Thrombotic thrombocytopenic purpura (TTP) is typically characterized by the symptomatic pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, and renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32699732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by a pentad consisting of thrombocytopenic, microangiopathic hemolytic anemia, renal dysfunction, neurological signs and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23767207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Clinical thrombotic thrombocytopenic purpura (TTP) is characterized by a pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal involvement, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10775033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "UNLABELLED: The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10541941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND: The pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12753286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Thrombotic thrombocytopenic purpura (TTP) is a disorder of blood coagulation that presents classically with the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction and mental status changes. How", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17525362", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 421, "text": "botic thrombocytopenic purpura has classically been characterized by the pentad of fever, microangiopathic hemolytic anemia, neurologic symptoms, renal dysfunction, and thrombocytopenia. The pat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11399382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterised by the clinical pentad of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia, renal failure, fluctuating neurologic signs, and fever. The a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9360410", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 397, "text": "hrombotic thrombocytopenic purpura was first described in 1924 by Moschowitz as a disease presenting with a pentad of signs and symptoms (anemia, thrombocytopenia, fever, hemiparesis and hematuria). Pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29340125", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 784, "text": "botic thrombocytopenic purpura (TTP) is a distinct, rare but potentially life-threatening entity that classically but not invariably presents with a pentad of acute onset haemolytic anaemia, thrombocytopenia, neurological symptoms, renal impairment and fevers. Autoimmun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30072561", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 286, "text": "s clinically characterized by the pentad of thrombocytopenia, Coombs-negative hemolytic anemia, fever, renal abnormalities and neurological disturbances. Advanc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21415981", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 641, "text": "t was diagnosed thrombotic thrombocytopenic purpura (TTP) following pentad of clinical features: microangiopathic hemolytic anemia, thrombocytopenia, fever neurologic, and renal abnormalities. Magnetic reso", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22574558", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 879, "text": "He was later diagnosed with thrombotic thrombocytopenic purpura (TTP) based on the fact that he presented with most components of the TTP pentad (except for fever), which included altered mental status, acute kidney injury, thrombocytopenia, and evidence of red cell fragmentation and his ADAMTS13 level was found to be less than 10% prior to therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25512716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening illness with disseminated platelet-rich thromboses of small vessels that variably presents with the classic clinical \"pentad\" of microangiopathic hemolytic anemia, thrombocytopenia, fever, altered mental status, and acute kidney injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29270999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Thrombotic thrombocytopenic purpura (TTP) is a rapidly progressive hematological syndrome defined by the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, fever and renal dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16913442", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 295, "text": "It is characterized by a pentad of clinical findings, including microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic and renal abnormalities, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2647685", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 270, "text": "It is a multi-systemic disorder characterized by a clinical pentad of thrombocytopenia, microangiopathic hemolytic anemia, diffuse and nonfocal neurologic symptoms, decreased renal function, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12745043", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 333, "text": "Initially presenting a fever and systemic upset she progressed to develop dialysis dependent acute renal failure, seizures, thrombocytopenia and a haemolytic anaemia--the pentad of features seen in TTP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16616715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Thrombotic thrombocytopenic purpura (TTP) consists of the pentad of thrombocytopenia, hemolytic anemia, fever, neurologic abnormalities, and renal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23738162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Thrombotic thrombocytopenic purpura is a clinical syndrome defined by the pentad of thrombocytopenia, microangiopathic hemolytic anemia, fever, and renal and neurologic abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8427289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "UNLABELLED: The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10541941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Thrombotic thrombocytopenic purpura (TTP) is characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, renal insufficiency, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12938786", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 327, "text": "It is characterized by the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, fever, and renal abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12423834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of unknown etiology, clinically characterized by a diagnostic pentad (thrombocytopenia, microangiopathic hemolytic anemia, neurologic signs and symptoms, fever and renal damage).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1821908", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 278, "text": "TTP is characterized by a pentad of clinical findings, including microangiopathic hemolytic anemia, thrombocytopenia, renal abnormalities, neurologic signs and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7863389", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 384, "text": "While the pentad of thrombocytopenia, microangiopathic hemolytic anemia, fever, and renal and neurologic abnormalities characterize the clinical presentation of TTP, few patients present with all signs and symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19665681", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 619, "text": " no cases of congenital TTP. The classic pentad of TTP (microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, renal dysfunction and fever) was", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23263974", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 579, "text": "TTP is a life-threatening disease, characterized by Moschcowitz's pentad: thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurological signs, renal failure, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16104532", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 867, "text": "1 This case presented with the pentad of thrombotic thrombocytopenic purpura: severe thrombocytopenia (platelets 9\u2009\u00d7\u2009109/L), microangiopathic haemolytic anaemia (reticular count 245\u2009\u00d7\u2009109/L (20-110)), LDH >5000 U/L (<425)), neurological abnormalities (Glasgow Coma Scale 10/15), renal failure (creatinine 140\u2009\u00b5mol/L (<97)), fever (37.7\u2103). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29123569", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 775, "text": "All 31 patients had diagnostic criteria for TTP; 16 (52%) had the complete \"pentad\" of microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal failure, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21850657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder characterized by a pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, fever, and a fluctuating neurologic syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18097325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "BACKGROUND: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare hematological emergency characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal injury, and fever that is invariably fatal if left untreated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26634125", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 337, "text": "Diagnosis of TTP is usually made on the basis of the pentad of anemia, thrombocytopenia, renal disease, neurologic abnormalities, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1171419", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1173, "text": "Later on he was referred to our intensive care unit; having classical pentad of thrombocytopenic purpura, i.e., thrombocytopenia, micro-angiopathic hemolytic anemia, renal failure, encephalopathy, and fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22233953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder which usually occurs in young adults. It is characterized by a pentad of clinical findings: fever, neurological abnormalities, renal dysfunction, microangiopathic hemolytic anemia and thrombocytopenia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4038757", "endSection": "abstract" } ] }, { "body": "What are organoids?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32865304", "http://www.ncbi.nlm.nih.gov/pubmed/33068633", "http://www.ncbi.nlm.nih.gov/pubmed/33241206", "http://www.ncbi.nlm.nih.gov/pubmed/32984947" ], "ideal_answer": [ "Organoids are 3D physiological in vitro structures that recapitulate morphological and functional features of in vivo tissues and offer significant advantages over traditional cell culture methods." ], "type": "summary", "id": "60491db71cb411341a00016e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Human cerebral organoids (HCOs) are an in vitro model of early neural development, aimed at modelling and understanding brain development and neurological disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33068633", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 413, "text": "To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32984947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Mammalian intestinal organoids are multicellular structures that closely resemble the structure of the intestinal epithelium and can be generated in vitro from intestinal stem cells under appropriate culture conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32865304", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 310, "text": "Organoids are 3D physiological in\u00a0vitro structures that recapitulate morphological and functional features of in\u00a0vivo tissues and offer significant advantages over traditional cell culture methods. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33241206", "endSection": "abstract" } ] }, { "body": "List 3 therapeutic uses for botulism toxin.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33008506", "http://www.ncbi.nlm.nih.gov/pubmed/20664247", "http://www.ncbi.nlm.nih.gov/pubmed/32923741", "http://www.ncbi.nlm.nih.gov/pubmed/17458494", "http://www.ncbi.nlm.nih.gov/pubmed/31579938", "http://www.ncbi.nlm.nih.gov/pubmed/31408270", "http://www.ncbi.nlm.nih.gov/pubmed/29173661", "http://www.ncbi.nlm.nih.gov/pubmed/19837283", "http://www.ncbi.nlm.nih.gov/pubmed/17119144" ], "ideal_answer": [ "Botulinum toxin injections are effective in relieving focal spasticity resulting from upper motor neuron injuries, migraine headaches, over active bladder and to relieve pain in the Sacroiliac Joint." ], "exact_answer": [ [ "migraine headaches" ], [ "focal spasticity resulting from upper motor neuron injuries" ], [ "Sacroiliac Joint pain", "pain relief" ], [ "overactive bladder", "urinary retention" ] ], "type": "list", "id": "601f0ed81cb411341a000070", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 127, "text": " Botulinum toxin injections are effective in relieving focal spasticity resulting from upper motor neuron injuries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31408270", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1005, "text": "Areas of controversy in treatment of migraine during pregnancy, including the use of magnesium, triptans vs butalbital combination medications, and onabotulinum toxin, are also explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31579938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "OnabotulinumtoxinA injection in the treatment of chronic migraine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33008506", "endSection": "title" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1340, "text": "and three open-label studies, namely the Chronic Migraine OnabotulinuMtoxinA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33008506", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1481, "text": "the REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33008506", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 732, "text": " Different sacroiliac joint injections have shown to provide pain relief in patients suffering this ailment. Various techniques for intraarticular injections, sacral branch blocks and radiofrequency ablation, both fluoroscopy guided and ultrasound guided are discussed in this paper. Less common techniques like prolotherapy, platelet rich plasma injections and botulism toxin injections are also discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29173661", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 377, "text": "Although botulinum toxin A is available by prescription for cosmetic and therapeutic use, no cases of botulism with detectable serum toxin have previously been attributed to cosmetic or therapeutic botulinum toxin injections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17119144", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 371, "text": "However, botulinum toxins also have therapeutic uses for medical conditions including strabismus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923741", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 987, "text": "linical manifestations and management of botulism are reviewed and botulinum toxin in the treatment of pediatric strabismus is discussed.Co", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "BOTOX injection to treat strabismus after infant botulism type B infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923741", "endSection": "title" }, { "offsetInBeginSection": 843, "offsetInEndSection": 1079, "text": "Botulinum toxin has been used in the treatment of numerous neuromuscular, autonomic, and sensory disorders since it was first approved for the management of strabismus and blepharospasm by the Food and Drug Administration (FDA) in 1989.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19837283", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1470, "text": "tions were explained for prostatic disorders. BoNT applications in urology are in the treatment of detrusor external sphincter dyssynergia, detrusor overactivity, detrusor underactivity, spastic conditions of the urethral sphincter, chronic prostate pain, interstitial cystitis, non-fibrotic bladder outflow obstruction (including benign prostatic hyperplasia) and acute urinary retention in women.CONCLUSI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20664247", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1325, "text": "To date, the toxin has been used to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17458494", "endSection": "abstract" } ] }, { "body": "What is the role of Tcf3 in the maintenance of pluripotency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23040478", "http://www.ncbi.nlm.nih.gov/pubmed/28288968", "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "http://www.ncbi.nlm.nih.gov/pubmed/30115631", "http://www.ncbi.nlm.nih.gov/pubmed/29513567", "http://www.ncbi.nlm.nih.gov/pubmed/21685889", "http://www.ncbi.nlm.nih.gov/pubmed/29299140", "http://www.ncbi.nlm.nih.gov/pubmed/23658527" ], "ideal_answer": [ "Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators. Tcf3 co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Tcf3 down-regulation modulates the lineage differentiation potential of mouse embryonic stem cells through Wnt signaling. Tcf3 down-regulation is a necessary step towards Wnt-mediated suppression of differentiation. Depletion of Tcf3 enables the maintenance of undifferentiated mouse ESCs.", "The maintenance of pluripotency in mouse embryonic stem cells relies on a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3 . We uncover a key role for post-translational regulation in the maintenance of pliospotency .", "The maintenance of pluripotency in mouse embryonic stem cells relies on a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3 . We found that down-regulation of Tlf3, a member of the Tcf/Lef family, represents a specific response to Wnt activation in ESCs . Further studies revealed that T cell factor 3 ( TCF3) is a potential downstream target of TERRA .", "The maintenance of pluripotency in mouse embryonic stem cells relies on a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3 . A recent report shows that \u03b2-catenin modulates the effect of TERRA in mESC maintenance ." ], "type": "summary", "id": "5fdb4148a43ad31278000018", "snippets": [ { "offsetInBeginSection": 759, "offsetInEndSection": 912, "text": "Accordingly, the transcripts of the pluripotency genes Esrrb, Tfcp2l1, and Klf2, repressed by TCF3 in mESCs, are increased in TERRA-overexpressing cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29513567", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 626, "text": "Further studies revealed that T cell factor 3 ( TCF3) is a potential downstream target of TERRA and mediates the effect of TERRA in mESC maintenance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29513567", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 361, "text": "One of these encodes T-cell factor 3 (TCF3), a transcription factor that plays important roles in ESC differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30115631", "endSection": "abstract" }, { "offsetInBeginSection": 724, "offsetInEndSection": 1037, "text": "Importantly, hnRNP H/F knockdown not only recapitulated the switch in TCF3 AS but also destabilized hESC colonies and induced differentiation. Providing an explanation for this, we show that expression of known TCF3 target E-cadherin, critical for maintaining ESC pluripotency, is repressed by E47 but not by E12.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30115631", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 557, "text": "the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 716, "text": "Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1104, "text": "Our results suggest that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18347094", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 783, "text": "Tcf3 localizes to many pluripotency genes in embryonic stem cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685889", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 911, "text": "Tcf3 acts as a transcriptional repressor and reveal that \u03b2-catenin directly abrogates Tcf3 function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Inhibition of glycogen synthase kinase-3 (Gsk3) supports mouse embryonic stem cells (ESCs) by modulating Tcf3, but the critical targets downstream of Tcf3 are unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040478", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 655, "text": "Conversely, forced expression phenocopied Gsk3 inhibition or Tcf3 deletion by suppressing differentiation and sustaining self-renewal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23040478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Wnt signaling regulates the lineage differentiation potential of mouse embryonic stem cells through Tcf3 down-regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "title" }, { "offsetInBeginSection": 693, "offsetInEndSection": 897, "text": "We found that down-regulation of Tcf3, a member of the Tcf/Lef family and a key player in the control of self-renewal and pluripotency, represents a specific and primary response to Wnt activation in ESCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1120, "text": "escuing Tcf3 expression partially restored the neural defects observed in Apc-mutant ESCs, suggesting that Tcf3 down-regulation is a necessary step towards Wnt-mediated suppression of neural differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "abstract" }, { "offsetInBeginSection": 1135, "offsetInEndSection": 1576, "text": "Tcf3 down-regulation in the context of constitutively active Wnt signaling does not result from promoter DNA methylation but is likely to be caused by a plethora of mechanisms at both the RNA and protein level as shown by the observed decrease in activating histone marks (H3K4me3 and H3-acetylation) and the upregulation of miR-211, a novel Wnt-regulated microRNA that targets Tcf3 and attenuates early neural differentiation in mouse ESCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "abstract" }, { "offsetInBeginSection": 1615, "offsetInEndSection": 1876, "text": "Wnt signaling down-regulates Tcf3 expression, possibly at both the transcriptional and post-transcriptional levels, and thus highlight a novel mechanism through which Wnt signaling inhibits neuro-ectodermal lineage differentiation in mouse embryonic stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658527", "endSection": "abstract" }, { "offsetInBeginSection": 760, "offsetInEndSection": 952, "text": "transcription factor 3 (TCF3), a target of miR-449a, could downregulate Nanog expression, and restoring TCF3 expression in miR-449a-expressing Nanog-negative cells abrogated cellular stemness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29299140", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 708, "text": "depletion of both Tcf3 and Lef1 enables maintenance of undifferentiated mouse ESCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28288968", "endSection": "abstract" } ] }, { "body": "What pathological condition is MK-1602 used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "http://www.ncbi.nlm.nih.gov/pubmed/29136283" ], "ideal_answer": [ "MK-1602 has been assessed in clinical trials for the acute treatment of migraine." ], "exact_answer": [ "acute treatment of migraine" ], "type": "factoid", "id": "6026d6891cb411341a0000cc", "snippets": [ { "offsetInBeginSection": 500, "offsetInEndSection": 643, "text": "Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 387, "text": "We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "AIM: The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27269043", "endSection": "title" } ] }, { "body": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28067910" ], "ideal_answer": [ "Yes. Genome-wide analyses indicate a association between mutations in ACVR1 and ulcerative colitis due to loss-of-function mutations in ADCY7.", "Yes. Sequencing analysis showed an association between mutations in ADCY7 and ulcerative colitis patients and high psychopathic traits.", "Yes. Genome-wide analyses indicate an association of alterations in ADCY7 and ulcerative colitis. Mutations in exon 2 interfere with the synthesis of the full-length isoform of CDKN2A and lead to the production of a shortened isoform, with significant morbidity and mortality.", "Yes, there is an association of alterations in ADCY7 and ulcerative colitis.", "To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, whole genomes of 4,280 patients were sequenced at low coverage and compared to 3,652 previously sequenced population controls across 73.5 million variants. A 0.6% frequency missense variant in ADCY7 was discovered that doubles the risk of ulcerative colitis." ], "exact_answer": "yes", "type": "yesno", "id": "60290a131cb411341a000109", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 734, "text": "To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at \u223c12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28067910", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of satralizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32797372", "http://www.ncbi.nlm.nih.gov/pubmed/33011853", "http://www.ncbi.nlm.nih.gov/pubmed/32228250", "http://www.ncbi.nlm.nih.gov/pubmed/32333898", "http://www.ncbi.nlm.nih.gov/pubmed/32306778", "http://www.ncbi.nlm.nih.gov/pubmed/31774956", "http://www.ncbi.nlm.nih.gov/pubmed/32731771", "http://www.ncbi.nlm.nih.gov/pubmed/32348222", "http://www.ncbi.nlm.nih.gov/pubmed/33301078", "http://www.ncbi.nlm.nih.gov/pubmed/30623348", "http://www.ncbi.nlm.nih.gov/pubmed/32304439", "http://www.ncbi.nlm.nih.gov/pubmed/33059216", "http://www.ncbi.nlm.nih.gov/pubmed/33167776" ], "ideal_answer": [ "Satralizumab is a humanized anti-interleukin-6 (IL-6) receptor monoclonal recycling antibody that has been approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD)." ], "type": "summary", "id": "60266cf31cb411341a0000c4", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Satralizumab (Enspryng\u00ae), a humanized anti-interleukin-6 (IL-6) receptor monoclonal recycling antibody, has been developed by Chugai Pharmaceutical and Roche for the treatment of neuromyelitis optica spectrum disorder (NMOSD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32797372", "endSection": "abstract" }, { "offsetInBeginSection": 521, "offsetInEndSection": 812, "text": "Monoclonal antibodies targeting terminal complement (eculizumab), CD19 (inebilizumab), and the interleukin-6 receptor (satralizumab) have demonstrated efficacy in NMOSD attack prevention in recent phase 3 trials and have gained subsequent regulatory approval in the USA and other countries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33301078", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 560, "text": "Two of these, the antiinterleukin 6 (IL-6) agents tocilizumab and satralizumab, have been studied in active NMOSD.O", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32348222", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 493, "text": "The interleukin-6 receptor inhibitor satralizumab and anti-CD19 antibody inebilizumab have published positive phase III trial results and await approval in the near future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32228250", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1379, "text": "Clinical trials of AQP4-IgG-positive NMOSD patients showed success with eculizumab (preventing cleavage of complement factor C5, thereby blocking formation of chemotactic C5a and membrane attack complex C9neo), inebilizumab (depleting CD19\u200a+\u200aB cells), and satralizumab (anti-IL-6R blocking IL-6 actions).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32304439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Introduction: Recent research has shown that IL-6 receptor (IL-6\u00a0R) inhibitors like tocilizumab and satralizumab are effective in reducing the relapse rate in patients with NMOSD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306778", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 955, "text": "SION: In NMOSD patients with antibodies against aquaporin 4, monoclonal antibodies that deplete B cells (rituximab and inebilizumab) or interfere with interleukin 6 signaling (tocilizumab and satralizumab) or complement activation (eculizumab) have superior efficacy compared to placebo. Tocil", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33011853", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 867, "text": " now have three agents indicated for the treatment of NMO including (eculizumab [Soliris\u00ae]), an anti-C5 complement inhibitor, satralizumab (ENSRYNG\u00ae), a monoclonal antibody against the IL-6 receptor (IL-6R) that blocks B cell antibody production and inebilizumab (Uplinza\u00ae), a monoclonal antibody that binds to the B-cell surface antigen CD19 with subsequent B and plasmablast cell lymphocytolysis with decreasing antibody production. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33059216", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 372, "text": "Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31774956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "BACKGROUND: Satralizumab, a humanised monoclonal antibody targeting the interleukin-6 receptor, reduced the risk of relapse in patients with neuromyelitis optica spectrum disorder (NMOSD) when added to immunosuppressant therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32333898", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 228, "text": "Satralizumab, a humanised monoclonal antibody targeting the interleukin-6 receptor, reduced the risk of relapse in patients with neuromyelitis optica spectrum disorder (NMOSD) when added to immunosuppressant therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32333898", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 253, "text": "Satralizumab, a humanized monoclonal antibody, was designed to treat NMOSD by targeting the IL-6 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33167776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Satralizumab (Enspryng\u00ae), a humanized anti-interleukin-6 (IL-6) receptor monoclonal recycling antibody, has been developed by Chugai Pharmaceutical and Roche for the treatment of neuromyelitis optica spectrum disorder (NMOSD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32797372", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 839, "text": "dicated agents for NMOSD. We now have three agents indicated for the treatment of NMO including (eculizumab [Soliris\u00ae]), an anti-C5 complement inhibitor, satralizumab (ENSRYNG\u00ae), a monoclonal antibody against the IL-6 receptor (IL-6R) that blocks B cell antibody production and inebilizumab (Uplinza\u00ae), a monoclonal antibody that binds to the B-cell surface antigen CD19 with subsequent B and plasmablast cell lymphocytolysis with decre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33059216", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1252, "text": "After the considerable progress on diagnosis, we are now close to class I evidence for a therapeutic effect of several drugs in NMO spectrum disorders, most notably with the anti-interleukin-6 receptor antibody (satralizumab) and anti-complement-5 antibody (eculizumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30623348", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 811, "text": "Some such drugs are the 2019-approved complement inhibitor eculizumab, other compounds in late development include its modified successor ravulizumab, IL-6 receptor antibody satralizumab, CD19 targeting antibody inebilizumab and the TACI-Fc fusion protein telitacicept.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32731771", "endSection": "abstract" } ] }, { "body": "Are mucin overexpression associated with disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31837357", "http://www.ncbi.nlm.nih.gov/pubmed/33300069", "http://www.ncbi.nlm.nih.gov/pubmed/31729101", "http://www.ncbi.nlm.nih.gov/pubmed/32195770" ], "ideal_answer": [ "Yes,\nmucins are overexpressed in various malignancies and inflammations." ], "exact_answer": "yes", "type": "yesno", "id": "604906ed1cb411341a000163", "snippets": [ { "offsetInBeginSection": 103, "offsetInEndSection": 309, "text": "The pathological mechanism underlying hepatolithiasis is closely related to bacterial infections of the intrahepatic bile duct, followed by chronic inflammation and the overexpression of mucin\u00a05AC (MUC5AC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "MUC1 is a membrane glycoprotein, which in adenocarninomas is overexpressed and exhibits truncated O-glycosylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31729101", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 86, "text": "Mucin 13 (MUC13) is reportedly overexpressed in human malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31837357", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 172, "text": "Inflammation causes MUC1 overexpression and hypoglycosylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32195770", "endSection": "abstract" } ] }, { "body": "What are the 4 types of holoprosencephaly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6431778", "http://www.ncbi.nlm.nih.gov/pubmed/17001700", "http://www.ncbi.nlm.nih.gov/pubmed/15301825", "http://www.ncbi.nlm.nih.gov/pubmed/28050387" ], "ideal_answer": [ "Holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the forebrain structures at various levels or to various degrees . Depending on the degree of involvement, it is classified into 4 types: Alobar, Semilobar, Lobar, and Middle interhemispheric fusion variant .", "Holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the forebrain structures at various levels or to various degrees. Depending on the degree of involvement, it is classified into 4 types: Alobar, Semilobar, Lobar and Middle interhemispheric fusion variant.", "The 4 types of holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the foremost structures at various levels or to varying degrees. Depending on the degree of involvement, it is divided into 4 types: Alobar, Halilobar, Lobar and Middle interhemispheric fusion variant.", "4 types of holoprosencephaly have been described: lobar, alobar, interhemispheric, sacral, and cerebellar.", "The 4 types of holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the foremost structures at various levels or to varying degrees. Depending on the degree of involvement, it is broken down into 4 types: Alobar, Halilobar, Lobar and Middle interhemispheric fusion variant.", "Four types of holoprosencephaly have been described: lobar, alobar, interhemispheric, and sacral. (PMID: 22990134)" ], "exact_answer": [ [ "Alobar holoprosencehaly" ], [ "semilobar holoprosencehaly", "" ], [ "lobar holoprosencehaly" ], [ "Middle interhemispheric fusion variant" ] ], "type": "list", "id": "601ec1fb1cb411341a000061", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the forebrain structures at various levels or to various degrees. Depending on the degree of involvement, it is classified into 4 types: Alobar, Semilobar, Lobar and Middle interhemispheric fusion variant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28050387", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 350, "text": "Neuroradiologic studies have provided detailed characteristics of four major types of holoprosencephaly: alobar, semilobar, lobar, and middle interhemispheric variant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15301825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 646, "text": "Holoprosencephaly is addressed under the following headings: alobar, semilobar, and lobar holoprosencephaly; arrhinencephaly; agenesis of the corpus callosum; pituitary abnormalities; hindbrain abnormalities; syntelencephaly; aprosencephaly/atelencephaly; neural tube defects; facial anomalies; median cleft lip; minor facial anomalies; single maxillary central incisor; holoprosencephaly-like phenotype; epidemiology; genetic causes of holoprosencephaly; teratogenic causes of holoprosencephaly; SHH mutations; ZIC2 mutations; SIX3 mutations; TGIF mutations; PTCH mutations; GLI2 mutations; FAST1 mutations; TDGF1 mutations; and DHCR7 mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17001700", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 297, "text": "The classifications of alobar, semilobar, and lobar types A and B holoprosencephaly are each represented, with an additional case of semilobar holoprosencephaly complicated by a subdural effusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6431778", "endSection": "abstract" } ] }, { "body": "Which yeast genes encode for condensin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26904946", "http://www.ncbi.nlm.nih.gov/pubmed/16100111", "http://www.ncbi.nlm.nih.gov/pubmed/12783798", "http://www.ncbi.nlm.nih.gov/pubmed/10811823", "http://www.ncbi.nlm.nih.gov/pubmed/25300489", "http://www.ncbi.nlm.nih.gov/pubmed/12719426", "http://www.ncbi.nlm.nih.gov/pubmed/11846874", "http://www.ncbi.nlm.nih.gov/pubmed/10749931", "http://www.ncbi.nlm.nih.gov/pubmed/10485849" ], "ideal_answer": [ "Smc2-Smc4 forms the core of the Saccharomyces cerevisiae condensin, which promotes metaphase chromosome compaction . Both SMC2 and SMC4 are essential for chromosome transmission in anaphase . Smc 2-8 suppresses catenanes accumulation, mitotic arrest and growth defects induced by histone depletion at semi-permissive temperature .", "Smc2/4 forms the core of the Saccharomyces cerevisiae condensin, which promotes metaphase chromosome compaction", "Condensin Smc2-Smc4 Dimers Are Flexible and Dynamic. Here, we probe the topology of Smc2-Smc4 dimers of the S. cerevisiae condensin complex with high-speed atomic force microscopy (AFM) in liquid Interestingly, SAC activation is suppressed by the absence of Top2 and Smc2, an essential component of condensin." ], "exact_answer": [ "Smc2/4" ], "type": "factoid", "id": "5fe31301a43ad31278000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Condensin Smc2-Smc4 Dimers Are Flexible and Dynamic.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26904946", "endSection": "title" }, { "offsetInBeginSection": 330, "offsetInEndSection": 472, "text": "Here, we probe the topology of Smc2-Smc4 dimers of the S. cerevisiae condensin complex with high-speed atomic force microscopy (AFM) in liquid", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26904946", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1183, "text": "Interestingly, SAC activation is suppressed by the absence of Top2 and Smc2, an essential component of condensin. Indeed, smc2-8 suppresses catenanes accumulation, mitotic arrest and growth defects induced by histone depletion at semi-permissive temperature", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25300489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "To better understand the contributions that the structural maintenance of chromosome proteins (SMCs) make to condensin activity, we have tested a number of biochemical, biophysical, and DNA-associated attributes of the Smc2p-Smc4p pair from budding yeast. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12719426", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Smc2/4 forms the core of the Saccharomyces cerevisiae condensin, which promotes metaphase chromosome compaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16100111", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 369, "text": "Both SMC2 and SMC4 are essential for chromosome transmission in anaphase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10811823", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 437, "text": "Here we demonstrate that three TTN genes encode chromosome scaffold proteins of the condensin (SMC2) and cohesin (SMC1 and SMC3) classes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11846874", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 448, "text": "we demonstrate that three TTN genes encode chromosome scaffold proteins of the condensin (SMC2) and cohesin (SMC1 and SMC3) classes. These prot", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11846874", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 784, "text": ", and Cnd3, three non-SMC subunits showing a high degree of sequence conservation to frog subunits, are essential for viability, and their gene disruption leads to a phenotype indistinguishable from that observed in cut3-477 and cut14-208, known mutations in SMC4 and SMC2-like subunits. Condensin subunit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10485849", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 361, "text": "e core subunits of the complex are members of the SMC2 (Structural Maintenance of Chromosomes) and SMC4 gene families. We ha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12783798", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 1075, "text": "Temperature-sensitive mutations of BRN1 can be suppressed by overexpression of a novel gene YCG1, which is homologous to another Xenopus condensin subunit, XCAP-G. Overexpression of SMC2, a gene necessary for chromosome condensation, and a homologue of the XCAP-E condensin, does not suppress brn1, pointing to functional specialization of components of the condensin complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10749931", "endSection": "abstract" } ] }, { "body": "What is another name for the drug AMG334?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28240610" ], "ideal_answer": [ "AMG334 is also called erenumab." ], "exact_answer": [ "Erenumab" ], "type": "factoid", "id": "6026ed981cb411341a0000d2", "snippets": [ { "offsetInBeginSection": 19, "offsetInEndSection": 396, "text": "The results of phase 2 randomized controlled trials for the prevention of episodic and chronic migraine demonstrating the efficacy and safety of four mAbs targeting the calcitonin gene-related peptide (CGRP) pathway [ALD403 (eptinezumab), AMG334 (erenumab), LY2951742 (galcanezumab) and TEV48125 (fremanezumab)] have been published recently, and phase 3 trials are in process. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28240610", "endSection": "abstract" } ] }, { "body": "Describe the genetic determinants of common epilepsies", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25087078" ], "ideal_answer": [ "Genetic determinants of common epilepsies are defined as the interaction of mutations in one of two unlinked genes, SCN1 and SCN2, which code for the proteins hamartin and epilepticin, respectively. Disruption of these genes has been found to be associated with epileptic encephalopathies, but it is not entirely clear if this translates directly to the increased risk for epilepsy or via epigenetic changes.", "The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. Meta-analysis of an all-epilepsy cohort identified loci at 2q24.3 (p=8\u00b771\u2008\u00d7\u200810(-10)), implicating SCN1A, and at 4p15.1 (p=5\u00b744\u2008\u00d7\u200810(-9)), harbouring PCDH7, which encodes a protocadherin molecule. For the cohort of genetic generalised epilepsy, a single signal at 2p16.1 (p=9\u00b799\u2008\u00d7\u200810(-9)), implicating VRK2 or FANCL was noted. Data suggest that specific loci can act pleiotropically raising risk for epilepsy broadly, or can have effects limited to a specific epilepsy subtype." ], "type": "summary", "id": "6028204c1cb411341a0000f6", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 2437, "text": "The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy).METHODS: We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1\u00b766\u2008\u00d7\u200810(-8).FINDINGS: We included 8696 cases and 26\u2008157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8\u00b771\u2008\u00d7\u200810(-10)), implicating SCN1A, and at 4p15.1 (p=5\u00b744\u2008\u00d7\u200810(-9)), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9\u00b799\u2008\u00d7\u200810(-9)), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy.INTERPRETATION: This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the ultimate aim of assisting in disease classification and prognosis. The data suggest that specific loci can act pleiotropically raising risk for epilepsy broadly, or can have effects limited to a specific epilepsy subtype. Future genetic analyses might benefit from both lumping (ie, grouping of epilepsy types together) or splitting (ie, analysis of specific clinical subtypes).FUNDING: International League Against Epilepsy and multiple governmental and philanthropic agencies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25087078", "endSection": "abstract" } ] }, { "body": "Should nerinetide be used for treatment of ischaemic stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32087818", "http://www.ncbi.nlm.nih.gov/pubmed/33148815" ], "ideal_answer": [ "Nerinetide did not improve the proportion of ischemic stroke patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo." ], "exact_answer": "no", "type": "yesno", "id": "6025fdf41cb411341a0000c0", "snippets": [ { "offsetInBeginSection": 2391, "offsetInEndSection": 2612, "text": "337 (61\u00b74%) of 549 patients with nerinetide and 329 (59\u00b72%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1\u00b704, 95% CI 0\u00b796-1\u00b714; p=0\u00b735). Secondary outcomes were similar between groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32087818", "endSection": "abstract" }, { "offsetInBeginSection": 2799, "offsetInEndSection": 2975, "text": "INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32087818", "endSection": "abstract" } ] }, { "body": "What is the role of alcohol acyl transferases in fruit aroma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16247561", "http://www.ncbi.nlm.nih.gov/pubmed/24661745", "http://www.ncbi.nlm.nih.gov/pubmed/11985619" ], "ideal_answer": [ "Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT).\nThe expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene." ], "type": "summary", "id": "6033fae11cb411341a00014d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Molecular and biochemical characteristics of a gene encoding an alcohol acyl-transferase involved in the generation of aroma volatile esters during melon ripening.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11985619", "endSection": "title" }, { "offsetInBeginSection": 1576, "offsetInEndSection": 1662, "text": "we conclude that CM-AAT1 plays a major role in aroma volatiles formation in the melon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11985619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16247561", "endSection": "abstract" }, { "offsetInBeginSection": 1348, "offsetInEndSection": 1587, "text": "The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16247561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The AAT1 locus is critical for the biosynthesis of esters contributing to 'ripe apple' flavour in 'Royal Gala' and 'Granny Smith' apples.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24661745", "endSection": "title" } ] }, { "body": "What is Hikikomori syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24056835", "http://www.ncbi.nlm.nih.gov/pubmed/20531124", "http://www.ncbi.nlm.nih.gov/pubmed/32985914", "http://www.ncbi.nlm.nih.gov/pubmed/24869848", "http://www.ncbi.nlm.nih.gov/pubmed/31542731", "http://www.ncbi.nlm.nih.gov/pubmed/29369656", "http://www.ncbi.nlm.nih.gov/pubmed/29188542", "http://www.ncbi.nlm.nih.gov/pubmed/32631267", "http://www.ncbi.nlm.nih.gov/pubmed/31305235", "http://www.ncbi.nlm.nih.gov/pubmed/29440704", "http://www.ncbi.nlm.nih.gov/pubmed/21706238", "http://www.ncbi.nlm.nih.gov/pubmed/29615267", "http://www.ncbi.nlm.nih.gov/pubmed/26973544", "http://www.ncbi.nlm.nih.gov/pubmed/25836972", "http://www.ncbi.nlm.nih.gov/pubmed/32913802" ], "ideal_answer": [ "The 'Hikikomori' syndrome (HS) consists of prolonged and severe social withdrawal.", "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social withdrawal in Japan. It is a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis.", "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social problem in Japan. It is a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis.", "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social problem in Japan. It's a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis.", "Hikikomori is a clinical condition in which a subject locks himself/herself into his/her own house for more than 6 months.", "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social withdrawal in Japan. It's a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis." ], "type": "summary", "id": "601d73501cb411341a00003b", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 203, "text": " Hikikomori, from the Japanese words 'hiku' (to pull) and 'komoru' (to withdraw), is a clinical condition in which a subject locks himself/herself into his/her own house for more than 6\u00a0months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32985914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The Characteristics and Social Functioning of Pathological Social Withdrawal, \"Hikikomori,\" in a Secondary Care Setting: a One-Year Cohort Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32631267", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND: Pathological social withdrawal, named \"Hikikomori,\" is a Japanese culture-bound syndrome and a serious social problem in Japan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32631267", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 668, "text": "Hikikomori, or severe social withdrawal, pertains to patients who have stopped participating in everyday routine and would spend the majority of time confined in their room for the period of 6 months or more, with no evident psychosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32913802", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 95, "text": "The 'Hikikomori' syndrome (HS) consists of prolonged and severe social withdrawal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31542731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "PURPOSE: To explore whether the 'hikikomori' syndrome (social withdrawal) described in Japan exists in other countries, and if so, how patients with the syndrome are diagnosed and treated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21706238", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 370, "text": "This study aims to determine the socio-demographic and clinical features and possible clinical subtypes that predict the 12-month outcomes of cases with hikikomori syndrome, a severe form of social withdrawal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29615267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "A 12-month study of the hikikomori syndrome of social withdrawal: Clinical characterization and different subtypes proposal.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29615267", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "INTRODUCTION: The 'Hikikomori' syndrome (HS) consists of prolonged and severe social withdrawal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31542731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Does the 'hikikomori' syndrome of social withdrawal exist outside Japan?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21706238", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "In 1998 the Japanese psychiatrist Tamaki Sait\u00afo invented the term hikikomori, referring to a condition characterised by a state of social withdrawal and avoidance (education, work, friendships) combined with a persistent isolation and confinement in the own home for at least 6 months, due to various factors. Init", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "BACKGROUND: Pathological social withdrawal, named \"Hikikomori,\" is a Japanese culture-bound syndrome and a serious social problem ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32631267", "endSection": "abstract" }, { "offsetInBeginSection": 679, "offsetInEndSection": 1015, "text": " history of social isolation, we diagnosed hikikomori syndrome according to the Japanese government's definition, which is as follows: lifestyle centered at home; no interest or willingness to attend school or work; persistence of symptoms beyond 6\u00a0months; and exclusion of other psychiatric and developmental disorders. Considering his", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29188542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "INTRODUCTION: The 'Hikikomori' syndrome (HS) consists of prolonged and severe social", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31542731", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Hikikomori, a Japanese culture-bound syndrome of social withdrawal?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20531124", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "A form of severe social withdrawal, called hikikomori, has been frequently described in Japan and is characterized by adolescents and young adults who become recluses in their parents' homes, unable to work or go to school for months or years. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20531124", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 374, "text": "n Japan, novel expressive forms of psychiatric phenomena such as \"modern-type depression\" and \"hikikomori\" (a syndrome of severe social withdrawal lasting for at least six months) have been reported especially among young people. Econom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25836972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: Pathological social withdrawal, named \"Hikikomori,\" is a Japanese culture-bound syndrome and a serious social problem in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32631267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "A form of severe social withdrawal, called hikikomori, has been frequently described in Japan and is characterized by adolescents and young adults who become recluses in their parents' homes, unable to work or go to school for months or years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20531124", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 384, "text": "Hikikomori is a Japanese word describing a condition that mainly affects adolescents or young adults who live isolated from the world, cloistered within their parents' homes, locked in their bedrooms for days, months, or even years on end, and refusing to communicate even with their family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26973544", "endSection": "abstract" }, { "offsetInBeginSection": 1169, "offsetInEndSection": 1417, "text": "However, a low ASA score was related to a psychological dysfunction in the Japanese cultural context; hikikomori symptoms, which are defined as a desire to remain in his or her own room and his or her understanding of this behavior in other people.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29369656", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Identification of the hikikomori syndrome of social withdrawal: Psychosocial features and treatment preferences in four countries.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869848", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "PURPOSE: To explore whether the 'hikikomori' syndrome (social withdrawal) described in Japan exists in other countries, and if so, how patients with the syndrome are diagnosed and treated.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21706238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Does the 'hikikomori' syndrome of social withdrawal exist outside Japan? A preliminary international investigation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21706238", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Hikikomori, a Japanese culture-bound syndrome of social withdrawal?: A proposal for DSM-5.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20531124", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Hikikomori, a severe form of social withdrawal syndrome, is a growing social issue in Japan and internationally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29440704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "BACKGROUND: Pathological social withdrawal, named \"Hikikomori,\" is a Japanese culture-bound syndrome and a serious social probl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32631267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "OBJECTIVE: Hikikomori, from the Japanese words 'hiku' (to pull) and 'komoru' (to withdraw), is a clinical condition in which a subject locks himself/herself into his/her own house for more tha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32985914", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 526, "text": "ea and the United States. Hikikomori was defined as a 6-month or longer period of spending almost all time at home and avoiding social situations and social relationships, associated with signif", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24869848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 309, "text": "In 1998 the Japanese psychiatrist Tamaki Sait\u00afo invented the term hikikomori, referring to a condition characterised by a state of social withdrawal and avoidance (education, work, friendships) combined with a persistent isolation and confinement in the own home for at least 6 months, due to various factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24056835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "PURPOSE: To explore whether the 'hikikomori' syndrome (social withdrawal) described in Japan exists in other countries, and if so, how patients with the syndrome are diagnosed and treated.METHODS: Two hikikomori case vignettes were sent to psychiatrists in Australia, Bangladesh, India, Iran, Japan, Korea, Taiwan, Tha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21706238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Hikikomori (social withdrawal that lasts six months or longer) is a growing problem among Japanese adolescents and young adults, with recent estimates that approximately 1% of Japanese youths will suffer from an episode of hikikomori in their lifetimes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31305235", "endSection": "abstract" } ] }, { "body": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25118508", "http://www.ncbi.nlm.nih.gov/pubmed/8988166", "http://www.ncbi.nlm.nih.gov/pubmed/8988167", "http://www.ncbi.nlm.nih.gov/pubmed/15923834", "http://www.ncbi.nlm.nih.gov/pubmed/10094188", "http://www.ncbi.nlm.nih.gov/pubmed/11314068", "http://www.ncbi.nlm.nih.gov/pubmed/10649491", "http://www.ncbi.nlm.nih.gov/pubmed/9215678", "http://www.ncbi.nlm.nih.gov/pubmed/17868088", "http://www.ncbi.nlm.nih.gov/pubmed/16502419", "http://www.ncbi.nlm.nih.gov/pubmed/15735646", "http://www.ncbi.nlm.nih.gov/pubmed/28521820", "http://www.ncbi.nlm.nih.gov/pubmed/9259286", "http://www.ncbi.nlm.nih.gov/pubmed/12221714", "http://www.ncbi.nlm.nih.gov/pubmed/19483581", "http://www.ncbi.nlm.nih.gov/pubmed/12116251", "http://www.ncbi.nlm.nih.gov/pubmed/28220539", "http://www.ncbi.nlm.nih.gov/pubmed/11772178", "http://www.ncbi.nlm.nih.gov/pubmed/22628249", "http://www.ncbi.nlm.nih.gov/pubmed/21814570", "http://www.ncbi.nlm.nih.gov/pubmed/24585549", "http://www.ncbi.nlm.nih.gov/pubmed/16251895", "http://www.ncbi.nlm.nih.gov/pubmed/11248247", "http://www.ncbi.nlm.nih.gov/pubmed/19952666", "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "http://www.ncbi.nlm.nih.gov/pubmed/22569119", "http://www.ncbi.nlm.nih.gov/pubmed/15880747", "http://www.ncbi.nlm.nih.gov/pubmed/14513358", "http://www.ncbi.nlm.nih.gov/pubmed/30040876", "http://www.ncbi.nlm.nih.gov/pubmed/21811467", "http://www.ncbi.nlm.nih.gov/pubmed/19860490", "http://www.ncbi.nlm.nih.gov/pubmed/29663378", "http://www.ncbi.nlm.nih.gov/pubmed/20125191", "http://www.ncbi.nlm.nih.gov/pubmed/19863427" ], "ideal_answer": [ "Saethre-Chotzen syndrome is a craniosynostosis syndrome that is rarely diagnosed prenatally . It is caused by cytogenetic deletions or mutations of the TWIST1 gene . Of the 37 patients with classic features of the syndrome, the overall detection rate for TWIST mutations was 68% . Increased risk for developmental delay is associated with TWIST deletions .", "Saethre-Chotzen syndrome is an autosomalomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1 . The majority of patients have mutations in TWIST gene, which codes for a basic helx-loix-loge transcription factor .", "Saethre-Chotzen syndrome (SCS), one of the most common forms of syndromic craniosynostosis (premature fusion of the cranial sutures), results from haploinsufficiency of TWIST1, caused by deletions of the entire gene or loss-of-function variants within the coding region.", "We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype. Mutations of the TWIST gene in the Saethre-Chotzen syndrome.", "It is caused by cytogenetic deletions or mutations of the TWIST1 gene. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype.", "Autosomal dominant mutations in the gene encoding the basic helix-loop-helix transcription factor Twist1 are associated with limb and craniofacial defects in humans with Saethre-Chotzen syndrome.", "Saethre-Chotzen syndrome is a craniosynostosis syndrome that is rarely diagnosed prenatally. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype.", "It is caused by cytogenetic deletions or mutations of the TWIST1 gene.", "Saethre-Chotzen syndrome is a craniosynostosis syndrome that is rarely diagnosed prenatally. It is caused by cytogenetic deletions or mutations of the TWIST1 gene. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype.", "Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1 . The majority of patients have mutations in TWIST gene on chromosome 7p21 . The most common cause of the syndrome is loss-of-function mutations in a genetic mutation in the TWIST 1 gene . The patient is a heterozygous carrier of the pathogenic variant c.415C>A .", "Saethre-Chotzen syndrome (SCS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the TWIST1 gene (transcription factor Xa, also known as T-box-binding protein 1).", "The Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1 . The majority of patients with the syndrome have mutations in TWIST gene . In 55 patients with features of the syndrome, 11% detected to have deletions by real-time gene dosage analysis .", "Mutations in the TWIST1 gene, encoding the syntaxin binding protein 1, have been described as the cause of the Saethre-Chotzen syndrome.", "Saethre-Chotzen syndrome (SCS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the TWIST1 gene." ], "exact_answer": [ "TWIST1" ], "type": "factoid", "id": "5fe08b77a43ad31278000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Saethre-Chotzen syndrome is a craniosynostosis syndrome that is rarely diagnosed prenatally. It is caused by cytogenetic deletions or mutations of the TWIST1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22569119", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 473, "text": "We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8988166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Mutations of the TWIST gene in the Saethre-Chotzen syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8988167", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 398, "text": "Saethre-Chotzen syndrome (acrocephalo-syndactyly type III, ACS III) is an autosomal dominant craniosynostosis with brachydactyly, soft tissue syndactyly and facial dysmorphism including ptosis, facial asymmetry and prominent ear crura. ACS III has been mapped to chromosome 7p21-22. Of interest, TWIST, the human counterpart of the murine Twist gene, has been localized on chromosome 7p21 as well. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8988167", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1348, "text": "Of the 37 patients with classic features of Saethre-Chotzen syndrome, the overall detection rate for TWIST mutations was 68%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14513358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14513358", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10094188", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Saethre-Chotzen syndrome (ACS III) is an autosomal dominant craniosynostosis syndrome recently ascribed to mutations in the TWIST gene, a basic helix-loop-helix (b-HLH) transcription factor regulating head mesenchyme cell development during cranial neural tube formation in mouse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10094188", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1278, "text": "Finally, since no TWIST mutations were detected in 40 cases of isolated coronal craniosynostosis, the present study suggests that TWIST mutations are specific to Saethre-Chotzen syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10094188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Mutations in the basic domain and the loop-helix II junction of TWIST abolish DNA binding in Saethre-Chotzen syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11248247", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Saethre-Chotzen syndrome is an autosomal dominant skull disorder resulting from premature fusion of coronal sutures (craniosynostosis). It is caused by mutations in the TWIST gene encoding a basic Helix-Loop-Helix transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11248247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Autosomal dominant mutations in the gene encoding the basic helix-loop-helix transcription factor Twist1 are associated with limb and craniofacial defects in humans with Saethre-Chotzen syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15735646", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 968, "text": "Notably, multiple Twist1 mutations associated with Saethre-Chotzen syndrome alter protein kinase A-mediated phosphorylation of Twist1, suggesting that misregulation of Twist1 dimerization through either stoichiometric or post-translational mechanisms underlies phenotypes of individuals with Saethre-Chotzen syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15735646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Saethre-Chotzen syndrome caused by TWIST 1 gene mutations", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16251895", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16251895", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 292, "text": "The purpose of this study was to use the genotypic diagnosis of the authors' series of patients with TWIST1-confirmed Saethre-Chotzen syndrome to describe their natural history and long-term surgical outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19952666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Saethre-Chotzen syndrome (SCS), one of the most common forms of syndromic craniosynostosis (premature fusion of the cranial sutures), results from haploinsufficiency of TWIST1, caused by deletions of the entire gene or loss-of-function variants within the coding region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30040876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostotic disorder characterized by coronal synostosis, facial asymmetry, ptosis, and limb abnormalities. Haploinsufficiency of TWIST1, a basic helix-loop-helix transcription factor is responsible for SCS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28220539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The majority of patients with Saethre-Chotzen syndrome have mutations in the TWIST gene, which codes for a basic helix-loop-helix transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14513358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND: Saethre-Chotzen syndrome is a syndromic craniosynostosis defined by a genetic mutation affecting the TWIST1 gene on chromosome 7p21.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19483581", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1261, "text": "The chromosome rearrangement downstream of TWIST is compatible with the notion that this is a Saethre-Chotzen syndrome gene and implies loss of function of one allele by a positional effect as a possible mechanism of mutation to evoke the syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9215678", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 343, "text": "The Saethre-Chotzen syndrome, which is defined by loss-of-function mutations in the TWIST gene, is the second most prevalent craniosynostosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21811467", "endSection": "abstract" }, { "offsetInBeginSection": 649, "offsetInEndSection": 890, "text": "The TWIST gene codes for a transcription factor containing a basic helix-loop-helix (b-HLH) motif and has recently been described as a candidate gene for Saethre-Chotzen syndrome, based on the detection of mutations within the coding region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9215678", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15735646", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Autosomal dominant mutations in the gene encoding the basic helix-loop-helix transcription factor Twist1 are associated with limb and craniofacial defects in humans with Saethre-Chotzen syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15735646", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 889, "text": " this region, the TWIST1 gene encoding a transcription factor was considered as a strong candidate gene since its haploinsufficiency is responsible for the human Saethre-Chotzen syndrome, characterized by skull coronal suture synostosis. Sequencin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21814570", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 396, "text": "loinsufficiency of the human TWIST1 gene, which causes the craniosynostosis disorder Saethre-Chotzen syndrome (SCS), is related to failure to repress transcription of CDKN1A (which encodes p21/WAF1/CIP1), promoting osteoblast differentiation. We have e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15880747", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 342, "text": " such gene that has been implicated in both syndromic (Saethre-Chotzen syndrome) and nonsyndromic forms of CS in humans is TWIST1. In thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24585549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Twist1 is the mouse ortholog of TWIST1, the human gene mutated in Saethre-Chotzen syndrome. P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17868088", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 270, "text": "rigenesis. Some loss-of-function mutations of the TWIST1 gene have been shown to cause an autosomal dominant craniosynostosis, known as the Saethre-Chotzen syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28521820", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 512, "text": "TWIST1 gene, detected by Multiplex Ligation Probe-dependent Amplification (MPLA) and array-CGH, was consistent with phenotype of Saethre-Chotzen syndrome. Array CGH also showe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22628249", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 943, "text": "eletion of 500 kb included the TWIST1 gene, a suggested candidate for RSTS that is responsible for the Saethre-Chotzen syndrome, an entity that enters in differential diagnosis with RSTS. A similar issue of d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20125191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Saethre-Chotzen syndrome (SCS), one of the most common forms of syndromic craniosynostosis (premature fusion of the cranial sutures), results from haploinsufficiency of TWIST1, caused by deletions of the entire gene or loss-of-function variants within the coding region. To det", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30040876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Saethre-Chotzen syndrome is associated with haploinsufficiency of the basic-helix-loop-helix (bHLH) transcription factor TWIST1 and is characterized by premature closure of the cranial sutures, termed craniosynostosis; however, the mechanisms underlying this defect are unclear. Twist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16502419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Saethre-Chotzen syndrome (ACS III) is an autosomal dominant craniosynostosis syndrome recently ascribed to mutations in the TWIST gene, a basic helix-loop-helix (b-HLH) transcription factor regulating head mesenchyme cell development during cranial neural tube formation in mouse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10094188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Contiguous gene deletion neighboring TWIST1 identified in a patient with Saethre-Chotzen syndrome associated with neurodevelopmental delay: Possible contribution of HDAC9.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28220539", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Prenatal diagnosis of craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3-7p15.3, including TWIST1 gene--a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25118508", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Saethre-Chotzen syndrome (SCS), associated with TWIST-1 mutations, is characterized by premature fusion of cranial sutures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29663378", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 411, "text": "Mice heterozygous for a null mutation of the Twist gene replicate certain features of Saethre-Chotzen syndrome, but have not been reported to exhibit craniosynostosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12221714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Saethre-Chotzen syndrome is an autosomal acrocephalosyndactyly syndrome whose gene has been assigned to chromosome 7p (TWIST).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11314068", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 902, "text": "Comprehensive studies in patients with the clinical diagnosis of Saethre-Chotzen syndrome have demonstrated a TWIST gene abnormality in about 80%, up to 37% of which may be large deletions [Johnson et al., 1998].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10649491", "endSection": "abstract" }, { "offsetInBeginSection": 1437, "offsetInEndSection": 1621, "text": "The authors conclude that when using stringent inclusion criteria for studies of Saethre-Chotzen syndrome, patients who have a pathogenic mutation of the TWIST gene should be excluded.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15923834", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 539, "text": "This case report describes a patient with Saethre-Chotzen syndrome caused by a mutation in the TWIST gene who exhibits a severe to profound sensorineural hearing loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11772178", "endSection": "abstract" }, { "offsetInBeginSection": 1326, "offsetInEndSection": 1422, "text": "Our results also indicate that the TWIST1 gene may be a novel breast cancer susceptibility gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1578, "text": "Additional studies are, however, necessary to reveal the mechanism by which TWIST1 may predispose to early onset breast cancer in Saethre-Chotzen patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 451, "text": "However, recent studies, using a murine breast tumor model, have shown that Twist may act as a key regulator of metastasis and that the gene is overexpressed in subsets of sporadic human breast cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17437280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "BACKGROUND: Saethre-Chotzen syndrome is a syndromic craniosynostosis defined by a genetic mutation affecting the TWIST1 gene on chro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19483581", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 202, "text": "Mutations in the TWIST gene have been identified in patients with Saethre-Chotzen syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10649491", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 1026, "text": "Of the patients with the Saethre-Chotzen phenotype, four were found to carry the FGFR3 P250R mutation, three were found to be heterozygous for three different novel mutations in the coding region of TWIST, and two were found to have a deletion of one copy of the entire TWIST gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12116251", "endSection": "abstract" }, { "offsetInBeginSection": 1345, "offsetInEndSection": 1467, "text": "Therefore, 9 of our 11 patients (82%) with the Saethre-Chotzen phenotype had detectable genetic changes in FGFR3 or TWIST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12116251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9259286", "endSection": "title" }, { "offsetInBeginSection": 660, "offsetInEndSection": 829, "text": "We report a young girl with clinical features of Saethre-Chotzen syndrome who has a previously undescribed sequence variant in the TWIST1 gene, corresponding to p.R191M.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19860490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16251895", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19863427", "endSection": "title" }, { "offsetInBeginSection": 124, "offsetInEndSection": 359, "text": "ormalities. It shows complete penetrance and variable expressivity and has been linked to the TWIST gene on chromosome 7p21; more than 80 different intragenic mutations and, recently, large deletions have been detected in Saethre-Chotz", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15923834", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 586, "text": "Furthermore, complete gene deletions of TWIST have also been found in a significant proportion of patients with Saethre-Chotzen syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12116251", "endSection": "abstract" } ] }, { "body": "List 4 targeted synthetic DMARDs that are JAK inhibitors.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31969328" ], "ideal_answer": [ "Targeted synthetic (ts) DMARDs that are Janus kinase (JAK) inhibitors include tofacitinib, baricitinib, filgotinib, upadacitinib." ], "exact_answer": [ [ "tofacitinib" ], [ "baricitinib" ], [ "filgotinib" ], [ "upadacitinib" ] ], "type": "list", "id": "6025a45b1cb411341a0000b5", "snippets": [ { "offsetInBeginSection": 730, "offsetInEndSection": 1251, "text": "The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31969328", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 1250, "text": "RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31969328", "endSection": "abstract" } ] }, { "body": "Which microRNAs are involved in targeting CYLD in triple negative breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30269739", "http://www.ncbi.nlm.nih.gov/pubmed/27476169" ], "ideal_answer": [ "Mir-182 and miR-301b are involved in targeting CYLD in triple negative breast cancer.", "MicroRNA-301b promotes cell proliferation and apoptosis resistance in triple-negative breast cancer by targeting CYLD. Knockdown of miR-182 up-regulates the expression of cylindromatosis (CYLD) deubiquitinase, which promotes the formation of death-inducing signaling complex (DISC) and subsequent caspase-8 activation in TNF-\u03b1-treated BT-549 cells." ], "exact_answer": [ [ "microRNA-301b" ], [ "microRNA-182", "miR-182" ] ], "type": "list", "id": "6026af5e1cb411341a0000c9", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "MicroRNA-301b promotes cell proliferation and apoptosis resistance in triple-negative breast cancer by targeting CYLD.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269739", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1527, "text": "Aberrant expression of microRNAs (miRNAs) plays important roles in carcinogenesis and tumor progression. However, the expression and biological role of miR-301b in triple-negative breast cancer (TNBC) remains unclear. Here we aimed to evaluate the roles and mechanisms of miR-301b in TNBC cells. miR-301b expression was assessed in TNBC specimens and cell lines by quantitative Real-Time PCR (qRT-PCR). TNBC cells were transfected with miR-301b mimics, inhibitors or Cylindromatosis (CYLD) small interfering RNA (siRNA) using Lipofectamine 2000. The functional roles of miR-301b were determined by cell proliferation, colony formation, and apoptosis assays. Western blots and qRT-PCR were used to measure the expression of mRNAs and proteins in the cells. We found that miR-301b was upregulated in TNBC specimens and cell lines. Overexpression of miR-301b promoted cell proliferation in TNBC cells, while inhibited the apoptosis induced by 5-FU. CYLD was downregulated by miR-301b at both mRNA and protein levels in TNBC cells. Dual-luciferase report assay confirmed that miR-301b downregulated CYLD by direct interaction with the 3'-untranslated region(3'-UTR) of CYLD mRNA. NF-\u03baB activation was mechanistically associated with miR-301b-mediated downregulation of CYLD. However, inhibition of miR-301b reversed all the effects of miR-301b. In conclusion, miR-301b plays an oncogenic role in TNBC possibly by downregulating CYLD and subsequently activating NF-\u03baB p65, and this may provide a novel therapeutic approach for TNBC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30269739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1356, "text": "Overexpression of microRNA-182 (miR-182) is found in multiple cancers, but the association of miR-182 expression with the sensitivity of triple-negative breast cancer (TNBC) cells to tumor necrosis factor-alpha (TNF-\u03b1) remains unknown. In this study, up-regulation of miR-182 was validated in TNBC patients and cell lines. Knockdown of miR-182 was observed to hinder the proliferation of BT-549 cells. More importantly, knockdown of miR-182 significantly promoted the apoptosis induced by TNF-\u03b1 treatment in BT-549. JC-1 staining and western blot assays revealed that the K63-linked ubiquitin chains on receptor-interacting protein 1 (RIP1) were removed and the outer mitochondrial membrane potential (MMP) and permeability was altered upon combination of TNF-\u03b1 with anti-miR-182. We then demonstrated that knockdown of miR-182 up-regulated the expression of cylindromatosis (CYLD) deubiquitinase, which promoted the formation of death-inducing signaling complex (DISC) and subsequent caspase-8 activation in TNF-\u03b1-treated BT-549 cells. Collectively, the results of the present study improve our understanding of the role of miR-182 in TNBC, knockdown of which facilitates the degradation of ubiquitin chains on RIP1, leading to the caspase-8 activation and apoptosis in TNF-\u03b1-treated TNBC cells. This may be valuable for the development of cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27476169", "endSection": "abstract" } ] }, { "body": "Which drugs were tested in the candor trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32682484", "http://www.ncbi.nlm.nih.gov/pubmed/32376237" ], "ideal_answer": [ "CANDOR trial investigated carfilzomib, dexamethasone, and daratumumab for patients with relapsed or refractory multiple myeloma." ], "exact_answer": [ [ "carfilzomib" ], [ "dexamethasone" ], [ "daratumumab" ] ], "type": "list", "id": "60274cd41cb411341a0000e4", "snippets": [ { "offsetInBeginSection": 623, "offsetInEndSection": 863, "text": "The Candor trial showed that the addition of daratumumab to carfilzomib and dexamethasone is associated with a significant benefit in progression-free survival among patients with relapsed/refractory MM after 1 to 3 prior lines of therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32376237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32682484", "endSection": "title" }, { "offsetInBeginSection": 325, "offsetInEndSection": 846, "text": "In this study, we aimed to compare the efficacy and safety of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma.METHODS: In this randomised, multicentre, open-label, phase 3 study, 466 patients recruited from 102 sites across North America, Europe, Australia, and Asia with relapsed or refractory multiple myeloma were randomly assigned 2:1 to carfilzomib, dexamethasone, and daratumumab (KdD) or carfilzomib and dexamethasone (Kd). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32682484", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 862, "text": "The Candor trial showed that the addition of daratumumab to carfilzomib and dexamethasone is associated with a significant benefit in progression-free survival among patients with relapsed/refractory MM after 1 to 3 prior lines of therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32376237", "endSection": "abstract" } ] }, { "body": "Which are the parts of a flaggelum?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33252734", "http://www.ncbi.nlm.nih.gov/pubmed/31940802", "http://www.ncbi.nlm.nih.gov/pubmed/31172377" ], "ideal_answer": [ "The bacterial flagellum is a supramolecular motility machine consisting of the basal body, the hook, and the filament.\nThe axial structure of the flagellum consists of the rod, hook, junction, filament, and cap." ], "exact_answer": [ [ "basal body" ], [ "hook" ], [ "filament" ], [ "cap" ] ], "type": "list", "id": "603281cb1cb411341a000140", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The bacterial flagellum is a supramolecular motility machine consisting of the basal body, the hook, and the filament. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31172377", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 521, "text": "The flagellum of Salmonella enterica serovar Typhimurium is composed of a bi-directional rotary motor, a universal joint and a helical propeller.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33252734", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 177, "text": "The axial structure of the flagellum consists of the rod, hook, junction, filament, and cap. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31940802", "endSection": "abstract" } ] }, { "body": "Why are male calico cats rare?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32574385", "http://www.ncbi.nlm.nih.gov/pubmed/13776765", "http://www.ncbi.nlm.nih.gov/pubmed/1163864" ], "ideal_answer": [ "The tortoiseshell coat color is characteristic to female cats, and its occurrence in tomcats is very rare and associated with the presence of an additional copy of X chromosome.", "The tortoishell coat colour is characteristic to female cats, and its occurrence in tom cats is very rare and associated with chromosome abnormalities." ], "type": "summary", "id": "601d742e1cb411341a000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The tortoiseshell coat colour is characteristic to female cats, and its occurrence in tomcats is very rare and associated with chromosome abnormalities (additional copy of X chromosome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32574385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "A review of the chromosome findings in 25 male tortoiseshell or calico (T-C) cats showed a variety of aneuploidy, polyploidy, mosaicism, and chimerism. An XXY-complement was included in the chromosome makeup of 16 of the 25 cats. Almost all of these cats were sterile. Testicular pathologic changes, when recorded, appeared comparable with that of human XXY Klinefelter's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1163864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "An animal model for the XXY Klinefelter's syndrome in man: tortoiseshell and calico male cats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1163864", "endSection": "title" }, { "offsetInBeginSection": 766, "offsetInEndSection": 958, "text": "An explanation of cat coat-color genetics clarified why \"black\" and sex-linked \"orange\" coloration can appear together normally in XX females and in rare males with 2 different X chromosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1163864", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 493, "text": "The findings in 2 male T-C cats were presented as representative models of XXY Klinefelter's syndrome in man. O", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1163864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "A review of the chromosome findings in 25 male tortoiseshell or calico (T-C) cats showed a variety of aneuploidy, polyploidy, mosaicism, and chimerism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1163864", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 262, "text": "The physical characteristics which suggested an abnormality of chromosome number in cats were \"calico\" or \"tortoise-shell\" coat colors in a male.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/13776765", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 266, "text": "he physical characteristics which suggested an abnormality of chromosome number in cats were \"calico\" or \"tortoise-shell\" coat colors in a male. Buc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/13776765", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 957, "text": "An explanation of cat coat-color genetics clarified why \"black\" and sex-linked \"orange\" coloration can appear together normally in XX females and in rare males with 2 different X chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1163864", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 491, "text": "The findings in 2 male T-C cats were presented as representative models of XXY Klinefelter's syndrome in man.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1163864", "endSection": "abstract" } ] }, { "body": "Which master regulator drives liver development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23607685", "http://www.ncbi.nlm.nih.gov/pubmed/20657840", "http://www.ncbi.nlm.nih.gov/pubmed/29234104", "http://www.ncbi.nlm.nih.gov/pubmed/29332143", "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "http://www.ncbi.nlm.nih.gov/pubmed/18462375", "http://www.ncbi.nlm.nih.gov/pubmed/30191603", "http://www.ncbi.nlm.nih.gov/pubmed/25043045", "http://www.ncbi.nlm.nih.gov/pubmed/25263553" ], "ideal_answer": [ "Hepatocyte nuclear factor (HNF)4\u03b1 regulates fetal liver development.", "The HNF4\u03b1 plays a major role in liver development, but it's not the only factor. There's a lot of other factors that play a role, but that's the big one." ], "exact_answer": [ "HNF4a", "Hepatocyte nuclear factor 4\u03b1" ], "type": "factoid", "id": "5fdb2e74a43ad3127800000d", "snippets": [ { "offsetInBeginSection": 5, "offsetInEndSection": 138, "text": "The molecular mechanisms by which hepatocyte nuclear factor (HNF)4\u03b1 regulates fetal liver development have not been fully elucidated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23607685", "endSection": "abstract" }, { "offsetInBeginSection": 1645, "offsetInEndSection": 1792, "text": "SNAT4 functions downstream of HNF4\u03b1 and plays significant roles in liver development through mechanisms of amino acid uptake and protein synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23607685", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 888, "text": "Here we use mouse genetics to address the role of UPF2, a core NMD component, in the development, function and regeneration of the liver. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20657840", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 813, "text": "Here we show that mutant IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2HG and suppression of HNF-4\u03b1, a master regulator of hepatocyte identity and quiescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25043045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Hepatocyte nuclear factor 4-alpha (HNF4\u03b1) is a well-established master regulator of liver development and function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29332143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Hepatocyte nuclear factor 4-alpha (HNF4\u03b1) is a well established master regulator of liver development and function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29234104", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 687, "text": "l-established master regulator of liver development and function, hepatocyte nuclear factor 4 alpha (HNF4\u03b1) plays a critical role in regulating a large number of key genes essential for the metabolism of xenobiotics, metabolic wastes, and nutrients. The expres", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 800, "offsetInEndSection": 984, "text": "PAX6), a master regulator of pancreas development overexpressed in colon cancer, cooperated with HNF1\u03b1 to induce P2-HNF4\u03b1 but antagonized HNF4\u03b1 in HNF4A-AS1 expression. Thus, PAX6 may ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191603", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 532, "text": "As a well-established master regulator of liver development and function, hepatocyte nuclear factor 4 alpha (HNF4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 676, "text": "As a well-established master regulator of liver development and function, hepatocyte nuclear factor 4 alpha (HNF4\u03b1) plays a critical role in regulating a large number of key genes essential for the metabolism of xenobiotics, metabolic wastes, and nutrients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1588, "text": "Herein I provide comprehensive review on the regulation of expression and transcriptional activity of HNF4\u03b1, and how HNF4\u03b1 crosstalks with diverse extracellular and intracellular signaling pathways to regulate genes essential in liver pathophysiology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1088, "text": "HNF4\u03b1 appears to play a central role in orchestrating the transduction of extracellular hormonal signaling and intracellular stress/nutritional signaling onto transcriptional changes in the liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1221, "text": "There have been a few reviews on the regulation of drug metabolism, lipid metabolism, cell proliferation, and inflammation by HNF4\u03b1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 1222, "offsetInEndSection": 1336, "text": "However, the knowledge on how the expression and transcriptional activity of HNF4\u03b1 is modulated remains scattered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 891, "text": "The expression and activity of HNF4\u03b1 is regulated by diverse hormonal and signaling pathways such as growth hormone, glucocorticoids, thyroid hormone, insulin, transforming growth factor-\u03b2, estrogen, and cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27709008", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 577, "text": "Using in vivo mouse liver development as a model, we identified thousands of enhancers that are bound by the master regulators HNF4A and FOXA2 in a differentiation-dependent manner, subject to chromatin remodeling, and associated with differentially expressed target genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Hepatocyte nuclear factor 4\u03b1 (HNF4\u03b1) is a master regulator of development and function of digestive tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30191603", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 875, "text": "The transcriptional regulation by these HNFs, which form a hierarchical and cooperative network, is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462375", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 632, "text": "Studies on the transcriptional regulatory elements of genes expressed in hepatocytes have identified several liver-enriched transcriptional factors, including hepatocyte nuclear factor (HNF)-1, HNF-3, HNF-4, HNF-6 and CCAAT/enhancer binding protein families, which are key components of the differentiation process for the fully functional liver.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462375", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1131, "text": "Among these liver-enriched transcription factors, HNF-4 is likely to act the furthest upstream as a master gene in transcriptional cascade and interacts with other liver-enriched transcriptional factors to stimulate hepatocyte-specific gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18462375", "endSection": "abstract" } ] }, { "body": "Are there small molecule CGRPs under development for the treatment of migraine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28644160" ], "ideal_answer": [ "Yes, there are several small molecule CGRPs under development for the treatment of migraine." ], "exact_answer": "yes", "type": "yesno", "id": "6026de661cb411341a0000d1", "snippets": [ { "offsetInBeginSection": 500, "offsetInEndSection": 643, "text": "Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 890, "text": "Several other small-molecular CGRP receptor antagonists are in earlier stages of development for acute migraine treatment or prevention. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" } ] }, { "body": "Which subcortical brain structure is influenced the most by common genetic variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25607358" ], "ideal_answer": [ "The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. Five novel genetic variants influencing the volumes of the putamen and caudate nucleus were identified. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08\u2009\u00d7\u200910(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue.", "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen and caudate nucleus, where a novel intergenic locus with replicative influence on volume and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohort.", "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945330; P = 1.08 \u00d7 10(-33); 0.52% variance explained. In caudate nucleus scientists have identified five novel genetic variants influenced the volumes of putamen and caudated nucleus.", "The putamen is the most affected by common genetic variants. It is the subcortical brain structure responsible for learning, memory and motivation.", "The putamen is the most influenced by common genetic variants. It is the subcortical brain structure responsible for learning, memory and motivation.", "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945280; P = 1.08 \u00d7 10(-33); 0.52% variance explained) showed evidence of altering the expression of theKTN1 gene in both brain and blood tissue. Variants affecting putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport.", "The putamen is the most influenced by common genetic variants. It is the subcortical brain structure responsible for learning and memory consolidation.", "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen and caudate nucleus, where a novel intergenic locus with replicable influence on volume and intracranial volume have been identified.", "The putamen is the most affected by common genetic variants. It is the subcortical brain structure responsible for learning and memory consolidation." ], "exact_answer": [ "Putamen" ], "type": "factoid", "id": "6028183e1cb411341a0000f1", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1489, "text": "The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08\u2009\u00d7\u200910(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25607358", "endSection": "abstract" } ] }, { "body": "Givosiran is used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "http://www.ncbi.nlm.nih.gov/pubmed/32521132", "http://www.ncbi.nlm.nih.gov/pubmed/33043761", "http://www.ncbi.nlm.nih.gov/pubmed/32034693", "http://www.ncbi.nlm.nih.gov/pubmed/31994716", "http://www.ncbi.nlm.nih.gov/pubmed/30847674", "http://www.ncbi.nlm.nih.gov/pubmed/33275677", "http://www.ncbi.nlm.nih.gov/pubmed/32592692", "http://www.ncbi.nlm.nih.gov/pubmed/30726693", "http://www.ncbi.nlm.nih.gov/pubmed/33139979" ], "ideal_answer": [ "Givosiran is approved for treatment of porphyria." ], "exact_answer": [ "porphyria" ], "type": "factoid", "id": "601c4b231cb411341a000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Cost savings with hemin versus givosiran for the treatment of patients with acute intermittent porphyria (AIP).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33043761", "endSection": "title" }, { "offsetInBeginSection": 98, "offsetInEndSection": 187, "text": " In 2019, FDA approved givosiran for the treatment of adults with acute hepatic porphyria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33043761", "endSection": "abstract" }, { "offsetInBeginSection": 1796, "offsetInEndSection": 1914, "text": "CONCLUSIONS: Hemin is expected to provide cost savings compared to givosiran for all AIP patients and subpopulations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33043761", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 936, "text": "New treatment options include givosiran (siRNA) to down-regulate ALA synthase-1 (ALAS1) and the messenger RNA of PBGD (PBGD mRNA) delivered to the liver cells of patients with AIP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33139979", "endSection": "abstract" }, { "offsetInBeginSection": 543, "offsetInEndSection": 837, "text": "Management of AIP includes awareness and avoidance of triggering factors, infusions of hemin for severe acute attacks, and, if indicated for chronic suppressive therapy, maintenance treatment with hemin or givosiran, a small interfering RNA molecule that antagonizes ALA synthase 1 transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33275677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 790, "text": "BACKGROUND: Induction of delta aminolevulinic acid synthase 1 ( ALAS1) gene expression and accumulation of neurotoxic intermediates result in neurovisceral attacks and disease manifestations in patients with acute intermittent porphyria, a rare inherited disease of heme biosynthesis. Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.METHODS: We conducted a phase 1 trial of givosiran in patients with acute intermittent porphyria. In part A of the trial, patients without recent porphyria attacks (i.e., no attacks in the 6 months before baseline) were randomly assigned to receive a single subcutaneous injection of one of five ascending doses of givosiran (0.035, 0.10, 0.35, 1.0, or 2.5 mg per kilogram of body weight) or placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30726693", "endSection": "abstract" }, { "offsetInBeginSection": 2029, "offsetInEndSection": 2374, "text": "CONCLUSIONS: Once-monthly injections of givosiran in patients who had recurrent porphyria attacks resulted in mainly low-grade adverse events, reductions in induced ALAS1 mRNA levels, nearly normalized levels of the neurotoxic intermediates delta aminolevulinic acid and porphobilinogen, and a lower attack rate than that observed with placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30726693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "In November 2019 givosiran became the second small interfering RNA (siRNA)-based drug to receive US Food and Drug Administration (FDA) approval, it has been developed for the treatment of acute intermittent porphyria (AIP), a disorder characterized by life-threatening acute neurovisceral attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1692, "text": "The clinical performance of givosiran revealed that suppression of ALAS1 by GalNac-decorated siRNAs represents an additional approach for the treatment of patients with AIP that manifests recurrent acute neurovisceral attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32521132", "endSection": "title" }, { "offsetInBeginSection": 373, "offsetInEndSection": 480, "text": "Givosiran is being developed by Alnylam Pharmaceuticals for the treatment of acute hepatic porphyria (AHP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32034693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Givosiran is a small interfering ribonucleic acid agent that was recently approved in the United States for the treatment of acute hepatic porphyria (AHP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31994716", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 487, "text": "This technology has led to the approval of givosiran for the treatment of acute hepatic porphyria, and there are another seven conjugates in registrational review or phase 3 trials and at least another 21 conjugates at earlier stages of clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32592692", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 649, "text": "In November 2019, givosiran was approved in the USA for the treatment of adults with AHP based on the positive results from the multinational, phase III ENVISION trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32034693", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1465, "text": "In preliminary results, givosiran achieved clinical endpoints for AIP, reducing urinary ALA levels, and presented a safety profile that enabled further drug development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31792921", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 360, "text": "This phase I study evaluated the safety, pharmacokinetic, and pharmacodynamic profile of subcutaneously (SC) administered givosiran in patients with acute intermittent porphyria, the most common AHP type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31994716", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1308, "text": "Givosiran, another RNAi therapeutic, targeting 5-aminolevulinic acid synthase, has been positively tested in acute intermittent porphyria in phase 1/2 and ongoing phase 3 trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30847674", "endSection": "abstract" } ] }, { "body": "List mediators that are released from mast cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31709696", "http://www.ncbi.nlm.nih.gov/pubmed/31722348", "http://www.ncbi.nlm.nih.gov/pubmed/18039527" ], "ideal_answer": [ "tryptase\nhistamine\nheparin proteoglycan\nchymase\ncytokines\n2,3-dinor-11\u03b2-PGF2\u03b1\nleukotriene (LT)E4" ], "exact_answer": [ [ "tryptase" ], [ "histamine" ], [ "heparin proteoglycan" ], [ "chymase" ], [ "cytokines" ], [ "2,3-dinor-11\u03b2-PGF2\u03b1" ], [ "leukotriene (LT)E4" ] ], "type": "list", "id": "604900391cb411341a000161", "snippets": [ { "offsetInBeginSection": 228, "offsetInEndSection": 331, "text": "Once mast cells are activated, beta-tryptase is released along with histamine and heparin proteoglycan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18039527", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 237, "text": "Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines, which all have important roles in the severity of dengue infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31709696", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 614, "text": "Mediators included serum tryptase plus urinary N-methyl histamine (N-MH), leukotriene (LT)E4, and 11\u03b2-prostaglandin (PG) F2\u03b1 or 2,3-dinor-11\u03b2-PGF2\u03b1 (BPG)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31722348", "endSection": "abstract" } ] }, { "body": "What is Exencephaly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18078364", "http://www.ncbi.nlm.nih.gov/pubmed/15517958", "http://www.ncbi.nlm.nih.gov/pubmed/7651715", "http://www.ncbi.nlm.nih.gov/pubmed/2303880", "http://www.ncbi.nlm.nih.gov/pubmed/1746228", "http://www.ncbi.nlm.nih.gov/pubmed/3054653", "http://www.ncbi.nlm.nih.gov/pubmed/3890003", "http://www.ncbi.nlm.nih.gov/pubmed/24902834" ], "ideal_answer": [ "Exencephaly is a type of cephalic disorder wherein the brain is located outside of the skull", "exencephaly, a failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue termed anencephaly. .", "exencephaly, a failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue termed anencephaly." ], "exact_answer": [ "a disorder where the brain is located outside of the skull", "failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue" ], "type": "factoid", "id": "601f027f1cb411341a00006b", "snippets": [ { "offsetInBeginSection": 678, "offsetInEndSection": 814, "text": "exencephaly, a failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue termed anencephaly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24902834", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1181, "text": "Exencephaly should be regarded as the most severe form of cranium bifidum, as myeloschisis is in spina bifida.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2303880", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 219, "text": "Exencephaly is an uncommon malformation of the cranium that characteristically involves a large, disorganized mass of cerebral tissue. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3054653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present despite the absence of the calvaria. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3890003", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 542, "text": "Exencephaly was characterized with the absence of normal echoes of the exocranium, the lateral ventricles, the chorioid plexus, the cerebral falx, and with the presence of deformed shape of the head and irregular, lobulated cerebral material with increasing volume at follow-up examination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7651715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Exencephaly/anencephaly is a rare neural tube defect occurring early in embryogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18078364", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 217, "text": "Exencephaly is an uncommon malformation of the cranium that characteristically involves a large, disorganized mass of cerebral tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3054653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Exencephaly is said to precede anencephaly resulting from failure of the rostral neuropore closure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1746228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present despite the absence of the calvaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3890003", "endSection": "abstract" } ] }, { "body": "What is the role of TNF in obesity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20357716", "http://www.ncbi.nlm.nih.gov/pubmed/24078163", "http://www.ncbi.nlm.nih.gov/pubmed/20173393", "http://www.ncbi.nlm.nih.gov/pubmed/17578885", "http://www.ncbi.nlm.nih.gov/pubmed/17088083", "http://www.ncbi.nlm.nih.gov/pubmed/10359811", "http://www.ncbi.nlm.nih.gov/pubmed/9832419", "http://www.ncbi.nlm.nih.gov/pubmed/8662983", "http://www.ncbi.nlm.nih.gov/pubmed/10668912", "http://www.ncbi.nlm.nih.gov/pubmed/10371192", "http://www.ncbi.nlm.nih.gov/pubmed/9644096", "http://www.ncbi.nlm.nih.gov/pubmed/30548217", "http://www.ncbi.nlm.nih.gov/pubmed/11126333", "http://www.ncbi.nlm.nih.gov/pubmed/9664082", "http://www.ncbi.nlm.nih.gov/pubmed/10395191", "http://www.ncbi.nlm.nih.gov/pubmed/15813957", "http://www.ncbi.nlm.nih.gov/pubmed/17020651", "http://www.ncbi.nlm.nih.gov/pubmed/9877261", "http://www.ncbi.nlm.nih.gov/pubmed/9137980", "http://www.ncbi.nlm.nih.gov/pubmed/17935818", "http://www.ncbi.nlm.nih.gov/pubmed/11334412", "http://www.ncbi.nlm.nih.gov/pubmed/9278582", "http://www.ncbi.nlm.nih.gov/pubmed/7678183", "http://www.ncbi.nlm.nih.gov/pubmed/30165404", "http://www.ncbi.nlm.nih.gov/pubmed/18339717", "http://www.ncbi.nlm.nih.gov/pubmed/15009470", "http://www.ncbi.nlm.nih.gov/pubmed/7926300", "http://www.ncbi.nlm.nih.gov/pubmed/7738205", "http://www.ncbi.nlm.nih.gov/pubmed/9335502", "http://www.ncbi.nlm.nih.gov/pubmed/9792545", "http://www.ncbi.nlm.nih.gov/pubmed/26113076", "http://www.ncbi.nlm.nih.gov/pubmed/8899294" ], "ideal_answer": [ "The role of TNF in obesity is not fully understood, but it is thought to play a major role in adipose tissue formation and fat storage. TNF-alpha is a protein that has been shown to increase fat storage in fat cells. It is also thought to have a role in insulin resistance.", "The role of TNF in obesity is not fully understood, but it is thought to play a major role in adipose tissue formation and fat storage. TNF-alpha is a protein that has been shown to increase fat storage in fat cells. It also has a role in insulin resistance, which is a major factor in obesity.", "TNF, acting via its receptors, is a major contributor to obesity-associated insulin resistance.", "Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity.", "TNFalpha gene overexpression induces insulin resistance. TNF-alpha is associated with obesity" ], "type": "summary", "id": "5fe31310a43ad31278000041", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578885", "endSection": "title" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1618, "text": "these data indicate that macrophage-derived TNF-alpha contributes to the pattern and extent of fat accumulation and insulin resistance in diet-induced obesity; however, this contribution is negligible in the presence of host-derived TNF-alpha.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17578885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Expression of TNF-alpha protein in omental and subcutaneous adipose tissue in obesity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17935818", "endSection": "title" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1223, "text": "TNF-alpha expression in omental adipose tissue could play a key role in contributing to cardiovascular risk in central obesity subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17935818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Influence of membrane-bound tumor necrosis factor (TNF)-alpha on obesity and glucose metabolism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15009470", "endSection": "title" }, { "offsetInBeginSection": 1243, "offsetInEndSection": 1397, "text": "Transmembrane TNF-alpha enhances adipose tissue formation without altering insulin-mediated glucose metabolism in mice with nutritionally induced obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15009470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Unaltered TNF-alpha production by macrophages and monocytes in diet-induced obesity in the rat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15813957", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Obesity and diabetes in TNF-alpha receptor- deficient mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9664082", "endSection": "title" }, { "offsetInBeginSection": 1382, "offsetInEndSection": 1478, "text": "TNF, acting via its receptors, is a major contributor to obesity-associated insulin resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9664082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Importance of TNF-alpha and leptin in obesity and insulin resistance: a hypothesis on the impact of physical exercise.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9644096", "endSection": "title" }, { "offsetInBeginSection": 480, "offsetInEndSection": 670, "text": "Elevated TNF-alpha expression induces insulin resistance by downregulating the tyrosine kinase activity of the insulin receptor and decreasing the expression of GLUT-4 glucose transporters. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9644096", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 478, "text": "In a more recently established hypothesis of body weight control and regulation of metabolism, the adipocyte secretes leptin and locally expresses TNF-alpha, the latter being responsible for the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression and TNF-alpha protein are greatly increased in adipose tissue from obese animals and humans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9644096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Serum concentrations of TNF-alpha and soluble TNF-alpha receptors in obesity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11126333", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 151, "text": "To study whether weight reducing treatment modulates serum concentration of TNF-alpha and two soluble TNF-alpha receptors in obese subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11126333", "endSection": "abstract" }, { "offsetInBeginSection": 781, "offsetInEndSection": 1000, "text": "The observed decrease of the serum concentration of TNF-alpha and the increase in both TNF soluble receptors after weight reducing treatment in obese subjects, may be a counter-regulation preventing further weight loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11126333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "The role of TNFalpha and TNF receptors in obesity and insulin resistance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10395191", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Microvascular endothelial dysfunction in human obesity: role of TNF-\u03b1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30165404", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Blockade of tumor necrosis factor (TNF) receptor type 1-mediated TNF-alpha signaling protected Wistar rats from diet-induced obesity and insulin resistance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18339717", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "TNF-alpha plays an important role in the pathogenesis of obesity and insulin resistance in which the effect of TNF-alpha signaling via TNF receptor type 1 (TNFR1) largely remains controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18339717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Functional analysis of tumor necrosis factor (TNF) receptors in TNF-alpha-mediated insulin resistance in genetic obesity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9832419", "endSection": "title" }, { "offsetInBeginSection": 1774, "offsetInEndSection": 1953, "text": "ON: These data indicate that plasma concentrations of both soluble TNF receptors are elevated in obesity and insulin resistance, possibly as a function of excess body fat. The rep", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9877261", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 472, "text": "has been suggested that tumour necrosis factor (TNF)-alpha is a candidate mediator of insulin resistance in obesity, as it is overexpressed in the adipose tissues of rodents and humans and it blocks the action of insulin in cultured cells and whole animals. To inv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9335502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The proinflammatory cytokine tumor necrosis factor (TNF) plays a central role in low-grade adipose tissue inflammation and development of insulin resistance during obesity. In ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26113076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "BACKGROUND: In obesity, increased tumor necrosis factor (TNF)-alpha level is involved in the development of insulin re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20357716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Tumor necrosis factor (TNF)-alpha plays a central role in the state of insulin resistance associated with obesity. It", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8662983", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "OBJECTIVE: Tumor necrosis factor (TNF)-alpha is thought to mediate, in part, the link between obesity and insulin resistance, and women with gestational diabetes mellitus (GDM) have raised serum TNF-alpha concentratio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17088083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Recent studies have shown that the tumor necrosis factor (TNF) system is implicated in the insulin resistance of human obesity. Pla", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9792545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Tumor necrosis factor (TNF)-alpha is one of the candidate mediators of insulin resistance associated with obesity, a major risk factor for the development of type 2 diabetes. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11334412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "The cytokine tumor necrosis factor alpha (TNF alpha) was proposed to mediate obesity related insulin resistance upon production in fat cells and to participate in tissue remodelling leading to vascular complications upon being released by macrophages. To ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9137980", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 637, "text": "The polymorpism of the TNF-a-308 gene is also involved in the development of obesity-related insulin resistance, therefore, we investigated whether the IRS-1 and TNF-a polymorphism can predict conversion to insulin resistance and obesity parameters in children with obesity.MATERIAL AND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17020651", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 435, "text": "In spite of the fact that this cytokine (also known as \"cachectin\") has been related to many of the metabolic abnormalities associated with cachexia, recent studies suggest that TNF may also have a central role in obesity modulating energy expenditure, fat deposition and insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10371192", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 465, "text": "It has been suggested that tumour necrosis factor (TNF)-alpha is a candidate mediator of insulin resistance in obesity, as it is overexpressed in the adipose tissues of rodents and humans and it blocks the action of insulin in cultured cells and whole animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9335502", "endSection": "abstract" }, { "offsetInBeginSection": 617, "offsetInEndSection": 849, "text": "In this study, we have analyzed the in vivo role of TNF signaling from p55 [TNF receptor (TNFR) 1] and p75 (TNFR 2) TNFR in the development of insulin resistance by generating genetically obese mice (ob/ob) lacking p55 or p75 TNFRs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9832419", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 604, "text": "In this cross-sectional study (n = 498; 258 males, 240 females), association of genotypes (PCR\u2013RFLP) of 11-\u03b2HSD1 and TNF-\u03b1 were analyzed with obesity [BMI \u2265 25 kg/m(2), percentage body fat (%BF by DEXA); subcutaneous and intra-abdominal fat area (L(2-3) level by single slice MRI) in a sub sample] and insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "11-\u03b2 hydroxysteroid dehydrogenase (11-\u03b2HSD1), tumor necrosis factor-\u03b1 (TNF-\u03b1) and their role in obesity, regional adiposity and insulin resistance has been sparsely evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24078163", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 679, "text": "To investigate the role of TNF-alpha in obesity and insulin resistance, we have generated obese mice with a targeted null mutation in the gene encoding TNF-alpha and those encoding the two receptors for TNF-alpha.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9335502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Inhibition of insulin receptor signaling by TNF: potential role in obesity and non-insulin-dependent diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8899294", "endSection": "title" }, { "offsetInBeginSection": 579, "offsetInEndSection": 734, "text": "Increased production of TNF by adipocytes, however, may contribute to insulin resistance in obesity and in non-insulin-dependent diabetes mellitus (NIDDM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8899294", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 980, "text": "TNF has been shown to inhibit insulin-simulated tyrosine phosphorylation of both the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and to stimulate downregulation of the insulin-sensitive glucose transporter, GLUT4, in adipocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8899294", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 589, "text": "Inflammatory cytokines such as tumor necrosis factor (TNF) can contribute to insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30548217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "TNF, but not hyperinsulinemia or hyperglycemia, is a key driver of obesity-induced monocytosis revealing that inflammatory monocytes correlate with insulin in obese male mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30548217", "endSection": "title" }, { "offsetInBeginSection": 191, "offsetInEndSection": 336, "text": "It is not clear if the extent of obesity, hyperinsulinemia, or hyperglycemia, underpins changes in cellular immunity during diet-induced obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30548217", "endSection": "abstract" }, { "offsetInBeginSection": 1113, "offsetInEndSection": 1236, "text": "Overall, TNF may function to make the subject less obese by inhibiting LPL and rendering the animal more insulin resistant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9278582", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1112, "text": "TNF is expressed at higher levels in muscle cells of insulin-resistant subjects, and TNF may inhibit LPL expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9278582", "endSection": "abstract" }, { "offsetInBeginSection": 841, "offsetInEndSection": 995, "text": "When insulin-resistant rodents were injected with anti-TNF binding protein, insulin action improved, suggesting a link between insulin resistance and TNF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9278582", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 602, "text": "These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7678183", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 265, "text": "Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7738205", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "TNF-alpha may play a role in mediating insulin resistance associated with obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9664082", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1201, "text": "These results indicate that TNF-alpha is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9335502", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Recent data have suggested a key role for tumor necrosis factor (TNF)-alpha in the insulin resistance of obesity and non-insulin-dependent diabetes mellitus (NIDDM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7926300", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 581, "text": "Although tumor necrosis factor alpha (TNF-alpha) has been implicated in the insulin resistance associated with obesity, its role in other disorders of obesity is largely unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10359811", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 393, "text": "Tumor necrosis factor-alpha (TNF-alpha) is overexpressed in obesity and is a candidate mediator of obesity-induced insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9832419", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1243, "text": "Such findings support the hypothesis that TNF is a mediator of obesity-linked insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10668912", "endSection": "abstract" }, { "offsetInBeginSection": 1400, "offsetInEndSection": 1637, "text": "This review will summarize the available knowledge on the role of TNF-alpha in obesity and related processes and the potential implications of the above in the development of new therapeutic approaches for obesity and insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173393", "endSection": "abstract" } ] }, { "body": "Is eptinezumab a small molecule?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32266704" ], "ideal_answer": [ "No, eptinezumab is a humanized monoclonal antibody." ], "exact_answer": "no", "type": "yesno", "id": "6026ee821cb411341a0000d3", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Eptinezumab-jjmr (referred to as eptinezumab hereafter; Vyepti\u2122) is a humanised monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and blocks its binding to the receptor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32266704", "endSection": "abstract" } ] }, { "body": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29218892", "http://www.ncbi.nlm.nih.gov/pubmed/29960671", "http://www.ncbi.nlm.nih.gov/pubmed/24399358", "http://www.ncbi.nlm.nih.gov/pubmed/26747746", "http://www.ncbi.nlm.nih.gov/pubmed/33044802", "http://www.ncbi.nlm.nih.gov/pubmed/31471575", "http://www.ncbi.nlm.nih.gov/pubmed/32470572", "http://www.ncbi.nlm.nih.gov/pubmed/28617224", "http://www.ncbi.nlm.nih.gov/pubmed/28426957", "http://www.ncbi.nlm.nih.gov/pubmed/32501580", "http://www.ncbi.nlm.nih.gov/pubmed/32198361", "http://www.ncbi.nlm.nih.gov/pubmed/29764998" ], "ideal_answer": [ "The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain.", "The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers", "The ENIGMA Consortium is a global team science effort, now including over 800 scientists spread across 340 institutions in 35 countries, with the shared goal of understanding disease and genetic influences on the brain.", "The Enhancing NeuroImaging genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,189 individuals have been provided by the Charcot-Marie-Tooth [CMT] Consortium for replication of findings, in a total of 24,997 subjects.", "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, they have detected factors that affect the brain that no individual site could detect on their own, and that require larger numbers of subjects than any individual study has currently collected.", "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, the consortium has detected factors that affect the brain that no individual site could detect on its own.", "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, they have detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual study has currently collected.", "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, they have detected factors that affect the brain that no individual site could detect on their own." ], "type": "summary", "id": "6028196e1cb411341a0000f2", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24399358", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1360, "text": "The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24399358", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 462, "text": "To overcome this problem, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, an international neuroimaging consortium, established standard protocols for imaging analysis and employs either meta- and mega-analyses of psychiatric disorders with large sample sizes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32501580", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 237, "text": "To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32470572", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 590, "text": "In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31471575", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Big data initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analysis consortium (ENIGMA), combine data collected by independent studies worldwide to achieve more generalizable estimates of effect sizes and more reliable and reproducible outcomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29218892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium is a global team science effort, now including over 800 scientists spread across 340 institutions in 35 countries, with the shared goal of understanding disease and genetic influences on the brain. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28426957", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 240, "text": "o overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. Ho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32470572", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 610, "text": "enter brain imaging consortia, such as the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, are interested in studying disease effects on these subregions, and in the genetic factors that affect them. For large-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26747746", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24399358", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 361, "text": "re, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29764998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Bu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32198361", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 383, "text": "Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33044802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "BACKGROUND: Global scale brain research collaborations such as the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium are beginning to collect data in large quantity and to conduct meta-analyses using uniforme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28617224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32198361", "endSection": "abstract" } ] }, { "body": "Inhaled Molgramostim can be used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29719809", "http://www.ncbi.nlm.nih.gov/pubmed/32897035" ], "ideal_answer": [ "Inhaled Molgramostim was shown to be effective for Autoimmune Pulmonary Alveolar Proteinosis." ], "exact_answer": [ "Autoimmune Pulmonary Alveolar Proteinosis" ], "type": "factoid", "id": "601cb5be1cb411341a000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897035", "endSection": "title" }, { "offsetInBeginSection": 420, "offsetInEndSection": 687, "text": "METHODS: In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 \u03bcg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897035", "endSection": "abstract" }, { "offsetInBeginSection": 2287, "offsetInEndSection": 2508, "text": "CONCLUSIONS: In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Autoimmune pulmonary alveolar proteinosis in an adolescent successfully treated with inhaled rhGM-CSF (molgramostim).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719809", "endSection": "title" }, { "offsetInBeginSection": 550, "offsetInEndSection": 731, "text": "We here describe a unique case of a 14-year-old patient who was successfully treated with WLL and subsequent inhalations with molgramostim - new recombinant human GM-CSF (rhGM-CSF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719809", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32897035", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Autoimmune pulmonary alveolar proteinosis in an adolescent successfully treated with inhaled rhGM-CSF (molgramostim)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29719809", "endSection": "title" } ] }, { "body": "Which are the main functions of the annexin family?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15590064", "http://www.ncbi.nlm.nih.gov/pubmed/28440436", "http://www.ncbi.nlm.nih.gov/pubmed/21131363", "http://www.ncbi.nlm.nih.gov/pubmed/29408340", "http://www.ncbi.nlm.nih.gov/pubmed/16210453", "http://www.ncbi.nlm.nih.gov/pubmed/27318360" ], "ideal_answer": [ "Annexins are required for membrane organization and membrane transport events required for the establishment/maintenance of epithelial polarity. \nAn association of annexins with ion channels, as membrane-guiding auxiliary proteins or modulators of channel activity. \nLast but not least, some annexins seem to work as extracellular autocrine modulators of receptor function under different physiological conditions." ], "exact_answer": [ [ "membrane organization and membrane transport events" ], [ "membrane-guiding auxiliary proteins or modulators of channel activity" ], [ "extracellular autocrine modulators of receptor function" ] ], "type": "list", "id": "60322d811cb411341a000138", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Annexins are a highly conserved protein family that bind to phospholipids in a calcium (Ca2+) - dependent manner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27318360", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 327, "text": "Highly conserved annexins may modulate the phagocytic cell removal by acting as bridging molecules to phosphatidylserine, a characteristic phagocytosis signal of dying cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21131363", "endSection": "abstract" }, { "offsetInBeginSection": 1315, "offsetInEndSection": 1449, "text": "the individual annexin repertoire bound to the cell surface of dying cells may fulfil opsonin-like function in cell death recognition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21131363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Annexins are a family of soluble proteins that bind to acidic phospholipids such as phosphatidylserine in a calcium-dependent manner. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29408340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Annexin\u00a0A2 is a member of the Annexin family that acts as a Ca2+-dependent phospholipid and membrane binding protein, which is associated with the survival and spread of multiple neoplasms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28440436", "endSection": "abstract" }, { "offsetInBeginSection": 989, "offsetInEndSection": 1135, "text": " underlying mechanisms specific for individual annexins, often supporting Ca2+ homeostasis and membrane transport as central for annexin biology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27318360", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 499, "text": "fueled speculations about the possible membrane-spanning forms of annexins that functioned as ion channels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29408340", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1201, "text": "potential role of Annexin\u00a0A2 in the prevention and treatment of ovarian cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28440436", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 979, "text": "irst, annexins are required for membrane organization and membrane transport events required for the establishment/maintenance of epithelial polarity. Second, there is accumulating evidence of an association of annexins with ion channels, as membrane-guiding auxiliary proteins or modulators of channel activity. Last but not least, some annexins seem to work as extracellular autocrine modulators of receptor function under different physiological conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16210453", "endSection": "abstract" } ] }, { "body": "Please list the 2 vaccines for herpes zoster(shingles)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31015813", "http://www.ncbi.nlm.nih.gov/pubmed/30558674", "http://www.ncbi.nlm.nih.gov/pubmed/31436592", "http://www.ncbi.nlm.nih.gov/pubmed/32284271", "http://www.ncbi.nlm.nih.gov/pubmed/29457489", "http://www.ncbi.nlm.nih.gov/pubmed/20113211", "http://www.ncbi.nlm.nih.gov/pubmed/32305975", "http://www.ncbi.nlm.nih.gov/pubmed/30179221", "http://www.ncbi.nlm.nih.gov/pubmed/22024532", "http://www.ncbi.nlm.nih.gov/pubmed/32999027", "http://www.ncbi.nlm.nih.gov/pubmed/23839657", "http://www.ncbi.nlm.nih.gov/pubmed/25144544", "http://www.ncbi.nlm.nih.gov/pubmed/16977285", "http://www.ncbi.nlm.nih.gov/pubmed/28426274", "http://www.ncbi.nlm.nih.gov/pubmed/31339679", "http://www.ncbi.nlm.nih.gov/pubmed/33294953", "http://www.ncbi.nlm.nih.gov/pubmed/29720364", "http://www.ncbi.nlm.nih.gov/pubmed/31061027", "http://www.ncbi.nlm.nih.gov/pubmed/24834646", "http://www.ncbi.nlm.nih.gov/pubmed/17326312", "http://www.ncbi.nlm.nih.gov/pubmed/27189459", "http://www.ncbi.nlm.nih.gov/pubmed/22086893" ], "ideal_answer": [ "live attenuated zoster vaccine (Zostavax\u00ae) and live attenuates herpes zoster (Shingles) are effective for treatment of infections with herpesZoster(shingles).", "live attenuated zoster vaccine (Zostavax; also known as shingles vaccine) is effective for prevention of infections with herpes zoster virus (VZV).", "Shingrix is a recombinant adjuvant subunit vaccine.", "The are 2 vaccines for herpes zoster, adjuvated recombinant vaccines and a live attenuated vaccine." ], "exact_answer": [ [ "live attenuated vaccine", "Zostervax", "LZV", "ZVL", "HZ" ], [ "adjuvated recombinant vaccine", "Shingrix", "RZV", "hz/su" ] ], "type": "list", "id": "601d6a651cb411341a000031", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Shingrix is a\u00a0recombinant adjuvant subunit vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33294953", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 436, "text": "Two different vaccines have been developed to prevent HZ; one is based on a live attenuated VZV strain (Zostavax), and the other is based on adjuvanted gE recombinant protein (Shingrix).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32999027", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 856, "text": "HZ prophylaxis has been strongly recommended in older adults through vaccination with a live attenuated vaccine, Zostavax\u00ae. A new recombinant subunit vaccine, HZ/su (Shingrix\u00ae), is the subject of this review. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31339679", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1011, "text": ": HZ/su is a new adjuvanted recombinant vaccine approved by the Food and Drug Administration for the prevention of herpes zoster in adults 50 years of age and older. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29457489", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 634, "text": "o review current evidence and develop guidance on whether the previously authorized LZV (Zostavax\u00ae) and/or the recently authorized RZV (Shingrix\u00ae) vaccine should be offered to Canadians 50 years of age and older", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31015813", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 410, "text": "wo HZ vaccines are currently authorized for use in those 50 years of age and older in Canada: a live attenuated zoster vaccine (LZV) authorized in 2008; and a recombinant subunit vaccine (RZV) authorized in October 2017.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31015813", "endSection": "abstract" }, { "offsetInBeginSection": 2722, "offsetInEndSection": 3232, "text": "Both vaccines have been shown to be safe and immunogenic and to reduce the incidence of HZ and post-herpetic neuralgia. Vaccine efficacy of LZV against HZ decreases with age at, and time since vaccination. The vaccine efficacy of RZV remains higher and appears to decline more slowly than vaccine efficacy of LZV across all age groups. Both vaccines are cost-effective in those 50 years of age and older compared with no vaccination, especially in those 65-79 years of age. RZV is more cost-effective than LZV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31015813", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 352, "text": " live attenuated herpes zoster vaccine (ZVL) in Australia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32284271", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 764, "text": "his new vaccine, which combines a single VZV glycoprotein (gE) and a multicomponent adjuvant, is superior to the previously available live attenuated VZV vaccine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32305975", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 374, "text": "recommending vaccination of adults 70 years of age (YOA) with the zoster vaccine live (ZVL), the only vaccine available at the time. The recently approved adjuvanted recombinant zoster vaccine (RZV) has a substantially different clinical profile that may offer additional benefits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31061027", "endSection": "abstract" }, { "offsetInBeginSection": 1704, "offsetInEndSection": 1870, "text": "Under the model assumptions, RZV is predicted to avert more HZ and PHN cases compared with ZVL. Results were robust under different scenario and sensitivity analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31061027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The recombinant zoster vaccine (Shingrix) was approved to help combat the incidence of shingles in patients age 50 years and older and the CDC now recommends it over the zoster vaccine live (Zostavax). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31436592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "INTRODUCTION: Zostavax, a live attenuated vaccine, has been approved in the United States for use in older individuals to reduce the risk and severity of herpes zoster (HZ), also known a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22024532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The live, attenuated shingles (herpes zoster) vaccine Zostavax(\u00ae) is approved in the EU for use in the prevention of herpes zoster and postherpetic neuralgia in adults aged \u226550 years. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23839657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "BACKGROUND: A new recombinant subunit vaccine for herpes zoster (HZ or shingles) was approved by the United States Food and Drug Administration on October 20, 2017 and is expected to replace the previous live attenuate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29720364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "A live attenuated varicella-zoster vaccine (Zostavax--Merck) has been approved by the FDA for prevention of herpes zoster (HZ; zoster; shingles) in persons > or = 60 years old. Ea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16977285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "A live attenuated vaccine to prevent herpes zoster, or shingles (Zostavax; Merck & Co Inc, Whitehouse Station, NJ), is approved by the US Food and Drug Administration (FDA) for use in adults aged 50 years or older. Studi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22086893", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 714, "text": "The authors characterized differences in the immunologic responses induced by two HZ vaccines, the live attenuated zoster vaccine (ZV) and the more recently developed adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit herpes zoster vaccine (HZ/su), in vaccine-naive subjects and those previously vaccinated with HZ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30179221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Zostavax, a live attenuated vaccine against shingles (herpes zoster) has been available in Switzerland since 2008.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24834646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "A live attenuated varicella-zoster vaccine (Zostavax--Merck) has been approved by the FDA for prevention of herpes zoster (HZ; zoster; shingles) in persons > or = 60 years old.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16977285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "A critical appraisal of 'Shingrix', a novel herpes zoster subunit vaccine (HZ/Su or GSK1437173A) for varicella zoster virus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28426274", "endSection": "title" }, { "offsetInBeginSection": 382, "offsetInEndSection": 601, "text": "The authors characterized differences in the immunologic responses induced by two HZ vaccines, the live attenuated zoster vaccine (ZV) and the more recently developed adjuvanted varicella-zoster virus (VZV) glycoprotein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30179221", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 857, "text": "The observed differences in responses paralleled the observed clinical protection of the two zoster vaccines, with HZ/su being superior to HZ.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30179221", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 1035, "text": "In order to clarify the value of each vaccine, de Boer and colleagues compare the cost-effectiveness of no vaccination, and of vaccination with Zostavax or the herpes zoster subunit vaccine in four cohorts of older adults from the perspective of the Netherlands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30558674", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 503, "text": "The recently available adjuvanted herpes zoster subunit vaccine Shingrix", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30558674", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 670, "text": "The herpes zoster subunit vaccine is more efficacious than Zostavax, and it can be administered to immunosuppressed individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30558674", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 430, "text": "A live-attenuated vaccine, Zostavax is not free of limitations, which include a relatively low efficacy that wanes over time and its contraindication among immunocompromised individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30558674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Herpes zoster vaccine (Zostavax [Merck & Co., Inc.]) was licensed in 2006 and recommended by the Advisory Committee on Immunization Practices (ACIP) in 2008 for prevention of herpes zoster (shingles) and its complications among adults aged \u226560 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25144544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "The live, attenuated shingles (herpes zoster) vaccine Zostavax(\u00ae) is approved in the EU for use in the prevention of herpes zoster and postherpetic neuralgia in adults aged \u226550 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23839657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Shingles (Herpes Zoster) Vaccine (Zostavax(\u00ae)): A Review in the Prevention of Herpes Zoster and Postherpetic Neuralgia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27189459", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Zostavax(\u00ae) is a live attenuated shingles (herpes zoster) vaccine approved in the EU for the prevention of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged \u226550 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27189459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Shingles (herpes zoster) vaccine (zostavax(\u00ae)): a review of its use in the prevention of herpes zoster and postherpetic neuralgia in adults aged \u226550 years.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23839657", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 33, "text": "Herpes zoster vaccine (Zostavax).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16977285", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "A new vaccine called Zostavax is available to reduce the risk of shingles (herpes zoster) in people ages 60 and older.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17326312", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 890, "text": " immunocompetent adults. The live attenuated zoster vaccine (Zostavax, Merck & Co., Inc.) is effective in preventing shingles in individuals 60 years of age and older and recommended by the Center for Disease Control's (CDC) Advisory Committee for Immunization Practices (ACIP).AREAS COVERED IN THIS REVIEW: Literature related to the live attenuated zoster vaccine is reviewed from its beginnings in the early 1970s through to the present.WHAT THE READER WILL GAIN: Background information on herpes zoster and up to date information on the live ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20113211", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 471, "text": "HZ/Su is the first subunit vaccine developed to protect against shingles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28426274", "endSection": "abstract" } ] }, { "body": "What is a likely origin of intronless genes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21620332", "http://www.ncbi.nlm.nih.gov/pubmed/10843807", "http://www.ncbi.nlm.nih.gov/pubmed/24820954", "http://www.ncbi.nlm.nih.gov/pubmed/13677319", "http://www.ncbi.nlm.nih.gov/pubmed/26415210", "http://www.ncbi.nlm.nih.gov/pubmed/22732409", "http://www.ncbi.nlm.nih.gov/pubmed/16469316", "http://www.ncbi.nlm.nih.gov/pubmed/15325254", "http://www.ncbi.nlm.nih.gov/pubmed/21860604" ], "ideal_answer": [ "More than half of SEGs identified in most of the species have at least one ortholog multiple exon gene in the same genome, which provides insight to their possible origin by retrotransposition", "There is strong support for the idea that retrotransposition followed by tandem duplications is the most probable event that can explain the expansion of intronless or single-exon genes (SEG) in eukaryotic organisms. More than half of SEGs identified in most of the species have at least one ortholog multiple exon gene in the same genome, which provides insight to their possible origin by retrotransposition.", "The origin of intronless genes is most likely retrotransposition", "Intronless genes (IGs) constitute approximately 3% of the human genome. Their origin is likely to be retrotransposition due to loss-of-function mutations or duplication.", "Genes without introns are a characteristic feature of prokaryotes, but there are still a number of intronless genes in eukaryotes. Most of these genes may have originated from retrotransposition rather than lineage-specific expansions of repeat elements." ], "exact_answer": [ "retrotransposition" ], "type": "factoid", "id": "5fdb4264a43ad31278000023", "snippets": [ { "offsetInBeginSection": 238, "offsetInEndSection": 340, "text": "These highly conserved intronless genes were found to be involved in essential housekeeping functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16469316", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Genes without introns are a characteristic feature of prokaryotes, but there are still a number of intronless genes in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21860604", "endSection": "abstract" }, { "offsetInBeginSection": 975, "offsetInEndSection": 1074, "text": "Part of intronless genes is derived from other intronless genes or multiexon genes in each species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21860604", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 656, "text": "Hexamer composition comparison allowed the definition of over- and under-represented motifs in intronless genes; surprisingly, experimental testing revealed that intron-lacking coding sequences are enriched rather than depleted in elements with splicing enhancement ability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15325254", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 232, "text": "ntronless genes, which constitute 3 percent of the human genome, differ from intron-containing genes in evolution and function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26415210", "endSection": "abstract" }, { "offsetInBeginSection": 1612, "offsetInEndSection": 1813, "text": "These results indicate that new SEGs are continuously and independently generated after species divergence over evolutionary time as evidenced by the phylogenetic results of single exon claudins genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21620332", "endSection": "abstract" }, { "offsetInBeginSection": 1910, "offsetInEndSection": 2084, "text": "strong support for the idea that retrotransposition followed by tandem duplications is the most probable event that can explain the expansion of SEGs in eukaryotic organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21620332", "endSection": "abstract" }, { "offsetInBeginSection": 1037, "offsetInEndSection": 1229, "text": "More than half of SEGs identified in most of the species have at least one ortholog multiple exon gene in the same genome, which provides insight to their possible origin by retrotransposition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21620332", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 755, "text": " IGs represent recent additions to the genome, created mostly by retroposition of processed mRNAs with retained functionality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732409", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 733, "text": "Evolutionary analysis revealed that 2601 intronless genes conserved among the three domains of life and 2323 intronless genes that had no homology with genes of other species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24820954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Intronless genes can arise by germline retrotransposition of a cDNA originating as mRNA from an intron-containing source gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10843807", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 919, "text": "We suggest that the intronless rho may have arisen through an ancient retrotransposition of a mature mRNA originating from errlo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/13677319", "endSection": "abstract" } ] }, { "body": "Which company developed ivosidenib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31660152" ], "ideal_answer": [ "Ivosidenib has been developed by Agios Pharmaceuticals." ], "exact_answer": [ "Agios Pharmaceuticals" ], "type": "factoid", "id": "6028fc841cb411341a000103", "snippets": [ { "offsetInBeginSection": 545, "offsetInEndSection": 836, "text": "Hence, enasidenib and ivosidenib, the IDH2 and IDH1 inhibitors developed by Agios Pharmaceuticals, have been approved by the Food and Drug Administration on 1 August 2017 and 20 July 2018 for the treatment of adult relapsed or refractory (R/R) AML with IDH2 and IDH1 mutations, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31660152", "endSection": "abstract" } ] }, { "body": "Is the apilimod inhibitor effective against SARS-CoV-2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32511357" ], "ideal_answer": [ "To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules were profiled. In a study the identification of 30 known drugs that inhibit viral replication was reportedd. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.", "Yes, apilimod inhibition is effective for treatment of SARS-CoV-2." ], "exact_answer": "yes", "type": "yesno", "id": "60324b771cb411341a000139", "snippets": [ { "offsetInBeginSection": 656, "offsetInEndSection": 1482, "text": "To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32511357", "endSection": "abstract" } ] }, { "body": "Is Lanabecestat effective for Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31764959", "http://www.ncbi.nlm.nih.gov/pubmed/33049114" ], "ideal_answer": [ "No. Treatment with lanabecestat was well tolerated and did not slow cognitive or functional decline of Alzheimer's disease patients." ], "exact_answer": "no", "type": "yesno", "id": "602673e91cb411341a0000c7", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33049114", "endSection": "abstract" }, { "offsetInBeginSection": 2940, "offsetInEndSection": 3063, "text": "Conclusions and Relevance: Treatment with lanabecestat was well tolerated and did not slow cognitive or functional decline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31764959", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33049114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheime", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33049114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "INTRODUCTION: The APECS and AMARANTH trials showed that beta-secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzhei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33049114", "endSection": "abstract" } ] }, { "body": "How is the STING protein activated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31928996", "http://www.ncbi.nlm.nih.gov/pubmed/31820985", "http://www.ncbi.nlm.nih.gov/pubmed/31896590", "http://www.ncbi.nlm.nih.gov/pubmed/31980485", "http://www.ncbi.nlm.nih.gov/pubmed/31991682" ], "ideal_answer": [ "During DNA virus infections, detection of cytosolic DNA by the cGAS-STING pathway leads to activation of IFN-\u03b2." ], "exact_answer": [ "By intracellular DNA" ], "type": "factoid", "id": "60490c421cb411341a000166", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Stimulator of interferon genes (STING) is an endoplasmic reticulum-localized adaptor protein (STING receptor) that has been shown to be activated by binding to natural cyclic dinucleotide (CDN) ligands and plays a vital role in innate immune sensing of exogenous or endogenous DNA, which then induces type I interferons and other cytokines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31820985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "During DNA virus infections, detection of cytosolic DNA by the cGAS-STING pathway leads to activation of IFN-\u03b2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31928996", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 373, "text": "Herpes simplex virus 1 (HSV-1) triggers both the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31896590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Detection of intracellular DNA by the cGAS-STING pathway activates a type I interferon-mediated innate immune response that protects from virus infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31980485", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Several DNA viruses have evolved antagonists to inhibit the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) DNA-sensing immune pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31991682", "endSection": "abstract" } ] }, { "body": "Explain the use of Radio Frequency Ablation as a treatment", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12376615", "http://www.ncbi.nlm.nih.gov/pubmed/15947578", "http://www.ncbi.nlm.nih.gov/pubmed/26361338", "http://www.ncbi.nlm.nih.gov/pubmed/12441927", "http://www.ncbi.nlm.nih.gov/pubmed/25992184", "http://www.ncbi.nlm.nih.gov/pubmed/31065438", "http://www.ncbi.nlm.nih.gov/pubmed/18670269", "http://www.ncbi.nlm.nih.gov/pubmed/7900601", "http://www.ncbi.nlm.nih.gov/pubmed/11110923", "http://www.ncbi.nlm.nih.gov/pubmed/30396206", "http://www.ncbi.nlm.nih.gov/pubmed/29372343", "http://www.ncbi.nlm.nih.gov/pubmed/1417404", "http://www.ncbi.nlm.nih.gov/pubmed/17981554", "http://www.ncbi.nlm.nih.gov/pubmed/21496837", "http://www.ncbi.nlm.nih.gov/pubmed/11779979", "http://www.ncbi.nlm.nih.gov/pubmed/25106899", "http://www.ncbi.nlm.nih.gov/pubmed/20017327", "http://www.ncbi.nlm.nih.gov/pubmed/11598245", "http://www.ncbi.nlm.nih.gov/pubmed/12751862", "http://www.ncbi.nlm.nih.gov/pubmed/10751849", "http://www.ncbi.nlm.nih.gov/pubmed/15663674", "http://www.ncbi.nlm.nih.gov/pubmed/31644405", "http://www.ncbi.nlm.nih.gov/pubmed/19357382", "http://www.ncbi.nlm.nih.gov/pubmed/32902841", "http://www.ncbi.nlm.nih.gov/pubmed/12418770", "http://www.ncbi.nlm.nih.gov/pubmed/25571196", "http://www.ncbi.nlm.nih.gov/pubmed/9480582", "http://www.ncbi.nlm.nih.gov/pubmed/22335865", "http://www.ncbi.nlm.nih.gov/pubmed/22357170", "http://www.ncbi.nlm.nih.gov/pubmed/7944863", "http://www.ncbi.nlm.nih.gov/pubmed/12441926", "http://www.ncbi.nlm.nih.gov/pubmed/18423723", "http://www.ncbi.nlm.nih.gov/pubmed/15749505", "http://www.ncbi.nlm.nih.gov/pubmed/26905020", "http://www.ncbi.nlm.nih.gov/pubmed/29696193" ], "ideal_answer": [ "Radio-frequency ablation (RFA) is a promising minimal-invasive treatment option for treatment of, cancer, pain, tissue hyperplasia and cardiac arrhythmias cancer, triggering tissue necrosis and results in reduced tumor volumes.", "Radiofrequency ablation is a simple, safe, and effective treatment option for the treatment of castration-resistant ovarian cancer.", "Radio frequency ablation is used in the treatment of infertility." ], "type": "summary", "id": "601ebc241cb411341a00005c", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 313, "text": "Radio-frequency ablation (RFA) is a promising minimal-invasive treatment option for early liver cancer, however monitoring or predicting the size of the resulting tissue necrosis during the RFA-procedure is a challenging task, potentially resulting in a significant rate of under- or over treatments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29696193", "endSection": "abstract" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1217, "text": "Endoscopy treatment includes a wide range of resection and ablative techniques, such as radio-frequency ablation (RFA), often concomitantly used in everyday endoscopy practice (multimodal therapy). RFA promotes mucosal necrosis of treated oesophagal region via high-frequency energy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31644405", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 341, "text": "Our aim was to evaluate the safety and efficacy of percutaneous radio frequency ablation (RFA) in reducing clinical symptoms, fibroid volume and improving laboratory parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32902841", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 619, "text": " Cooled radio frequency ablation (C-RFA) is a treatment with the potential to provide pain relief for patients who no longer benefit from noninvasive modalities and who desire an alternative to surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30396206", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 337, "text": "Peripheral nerve pain is common among patients with typical management including the use of pain medications, neuropathic agents, steroid injections, and nerve blocks. Additionally, the use of pulsed radiofrequency (PRF) and radiofrequency ablation (RFA) can be used in the management of chronic peripheral nerve pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29372343", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 549, "text": "Previous studies investigating the effectiveness of RFA and PRF, typically case reports, have demonstrated that peripheral nerve RFA and PRF have the potential to provide relief of chronic pain for long duration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29372343", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 631, "text": "Our study aimed at testing efficacy of RFA/PRF for treating peripheral neuralgia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29372343", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1533, "text": "RFA and PRF can be used to treat chronic peripheral pain after conservative methods fail to do so. Large clinical trials are needed to confirm our finding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29372343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Radiofrequency ablation (RFA) is an important standard therapy for cardiac arrhythmias, but direct monitoring of tissue treatment is currently lacking. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31065438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "OBJECTIVE: To evaluate the feasibility of sonographically guided radio frequency thermal ablation as a minimally invasive method for treatment of unresectable recurrent or metastatic tumors in the retroperitoneum and the pelvis, which often pose difficult surgical problems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12751862", "endSection": "abstract" }, { "offsetInBeginSection": 1686, "offsetInEndSection": 1901, "text": "SIONS: Minimally invasive sonographically guided radio frequency thermal ablation is technically feasible for local treatment of unresectable recurrent retroperitoneal and pelvic tumors from different origins. Care ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12751862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "PURPOSE: Radio frequency ablation is an emerging nephron sparing treatment option in select patients with small renal tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18423723", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 417, "text": "TERIALS AND METHODS: We identified 159 tumors treated with radio frequency ablation as primary treatment. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22335865", "endSection": "abstract" }, { "offsetInBeginSection": 1420, "offsetInEndSection": 1539, "text": "SIONS: Radio frequency ablation treatment success of the small renal mass is strongly correlated with tumor size. Radio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22335865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "PURPOSE: To evaluate the feasibility of a technique of MR-guided stereotactic radio frequency ablation, which was developed as a minimally invasive treatment for brain tumors, and to determine MR characteristics and sequential evolution of radio frequency lesions created to ablate brain tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7900601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Tumor ablation by using radio-frequency energy has begun to receive increased attention as an effective minimally invasive approach for the treatment of patients with a variety of primary and secondary malignant neoplasms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11110923", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 898, "text": "radio-frequency ablation has been shown to be an effective method to treat BE, although there is disagreement as to whether radio-frequency ablation should be used to treat all patients with BE or whether treatment should be reserved for those at high risk for progressing to esophageal adenocarcinoma while continuing to endoscopically survey those with low risk. Recent res", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25992184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 380, "text": "The series of five patients with symptomatic isolated right ventricular outflow tract ectopy and no structural heart disease which were successfully treated with radiofrequency ablation of the ectopic focus are reported in order to discuss radio-frequency ablation as an alternative treatment in patients with right ventricular outflow tract ectopy without ventricular tachycardia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9480582", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 506, "text": "adio-Frequency Ablation (RFA) is a minimally invasive technique which is used as standard local therapy of primary and metastatic liver tumors. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17981554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Minimally-invasive treatments of cardiac arrhythmias such as radio-frequency ablation are gradually gaining importance in clinical practice but still lack a noninvasive imaging modality which provides insight into the source or focus of an arrhythmia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26361338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "BACKGROUND AND PURPOSE: Combining percutaneous plasma-mediated radio-frequency (pmRF) ablation with vertebral body augmentation offers an alternative treatment to surgical intervention options for advanced metastatic spinal lesions and is particularly useful for cases with cortical destruction and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19357382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Recently, Radio Frequency Ablation (RFA) is becoming a popular therapy for various cancers such as liver, breast, or lung cancer. RFA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25571196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "OBJECTIVE: Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15663674", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 887, "text": "Recently, radio-frequency ablation has been shown to be an effective method to treat BE, although there is disagreement as to whether radio-frequency ablation should be used to treat all patients with BE or whether treatment should be reserved for those at high risk for progressing to esophageal adenocarcinoma while continuing to endoscopically survey those with low risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25992184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 381, "text": "The series of five patients with symptomatic isolated right ventricular outflow tract ectopy and no structural heart disease which were successfully treated with radiofrequency ablation of the ectopic focus are reported in order to discuss radio-frequency ablation as an alternative treatment in patients with right ventricular outflow tract ectopy without ventricular tachycardia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9480582", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 541, "text": "SETTING: Teaching hospital.PATIENT(S): Women suffering from dysfunctional uterine bleeding.INTERVENTION(S): Bipolar radio frequency ablation and thermal balloon ablation.MAIN OUTCOME MEASURE(S): Patients were asked to complete HRQoL questionnaires at baseline, and at 2 days, 2 weeks, 3 months, 6 months, and 12 months after surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15749505", "endSection": "abstract" }, { "offsetInBeginSection": 426, "offsetInEndSection": 731, "text": "METHODS: We reviewed our radio frequency ablation database of patients with renal masses undergoing laparoscopic or computerized tomography guided percutaneous radio frequency ablation with simultaneous peripheral fiberoptic thermometry from November 2001 to January 2011 at a single tertiary care center.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357170", "endSection": "abstract" }, { "offsetInBeginSection": 1458, "offsetInEndSection": 1766, "text": "Subanalysis of the 212 (67%) renal cell carcinoma tumors showed a 3-year Kaplan-Meier estimation of oncologic recurrence-free probability (post-ablation biopsy proven viable tumor) of 94% for computerized tomography guided radio frequency ablation and 100% for laparoscopic radio frequency ablation (p=0.16).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357170", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 620, "text": "They were organized into five categories: understanding the mechanisms and principles of radio-frequency ablation, modulation of tissue physiologic characteristics to increase tumor destruction, strategies of overlapping ablations, strategies to improve ablation according to tumor location, and imaging strategies after ablation to ensure adequate therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11598245", "endSection": "abstract" }, { "offsetInBeginSection": 1414, "offsetInEndSection": 1533, "text": "CONCLUSIONS: Radio frequency ablation treatment success of the small renal mass is strongly correlated with tumor size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22335865", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 544, "text": "Following surgical exposure of the kidney a single 12-minute radio frequency ablation of the tumor was performed using the Radionics Cool-tip RF Radio Frequency Ablation System (Radionics, Burlington, Massachusetts).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12441926", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1623, "text": "Compared with the laparoscopic partial nephrectomy group, patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a smaller decrease in glomerular filtration rate of the affected kidney at 3 months (10.2% vs 20.5%, p=0.001) and 12 months (7.6% vs 16.2%, p=0.002).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26905020", "endSection": "abstract" }, { "offsetInBeginSection": 1365, "offsetInEndSection": 1615, "text": "This review aims to explain distinct effects of PPIs and RFA modalities, illuminate certain aspects of molecular mechanisms involved, as well as the effects of their concomitant use regarding the treatment of BE and prevention of its transfer to EAC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31644405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "OBJECTIVE: To explore the clinical value of CT guided radio frequency ablation in the treatment of pelvis tumor.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20017327", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 409, "text": "1 males and 8 females ranging from 25 to 49 years old (average 37) were enrolled in this study, all the 19 patients were suffering from pelvis tumor including giant cell tumor of bone (2/19), Ewing's sarcoma (2/19), malignant fibrous histiocytoma (3/19) and metastatic diseases (12/19). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20017327", "endSection": "abstract" }, { "offsetInBeginSection": 1266, "offsetInEndSection": 1388, "text": "yoablation and radio frequency ablation are effective treatment modalities for small renal masses in the infirm patient. G", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18670269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Probe ablative treatment for small renal masses: cryoablation vs. radio frequency ablation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18670269", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Radio frequency ablation is an effective treatment for focal renal cell carcinoma (RCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12418770", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 512, "text": "atients. We present our experience with radio frequency interstitial tissue ablation, a heating device approved by the Food and Drug Administration for treating soft tissue tumors.MATERIALS AND METHODS: Patients underwent radio frequency interstitial tissue ablation of small renal tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10751849", "endSection": "abstract" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 1826, "text": "hey required more frequent intervention. Radio frequency ablation became the most widely used second or third line procedure and allowed renal salvage in 8 patients.CONCLUSIONS: Nephron sparing surgery and more recently radio frequency ablation enable earlier treatment of smaller tumors and are associated with a significant improved renal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21496837", "endSection": "abstract" }, { "offsetInBeginSection": 1332, "offsetInEndSection": 1581, "text": "examined with hematoxylin and eosin or NADH staining. We believe that radio frequency interstitial tumor ablation of renal cell carcinoma without subsequent tissue resection should continue to be an investigational treatment modality for those who w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12441927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 425, "text": "PURPOSE: To evaluate the feasibility of a technique of MR-guided stereotactic radio frequency ablation, which was developed as a minimally invasive treatment for brain tumors, and to determine MR characteristics and sequential evolution of radio frequency lesions created to ablate brain tumors.METHODS: Fourteen lesions in 12 patients with primary and metastatic brain tumors were treated with this technique and followed fo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7900601", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 454, "text": "OBJECTIVE: To evaluate the feasibility of sonographically guided radio frequency thermal ablation as a minimally invasive method for treatment of unresectable recurrent or metastatic tumors in the retroperitoneum and the pelvis, which often pose difficult surgical problems.METHODS: Radio frequency thermal ablation was performed on 7 patients with unresectable recurrent retroperitoneal or pelvic tumors from colorectal (n = 4), renal (n = 2), and prost", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12751862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "[Ablation by radiofrequency in the treatment of atrial arrhythmia].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7944863", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 331, "text": "PURPOSE: We defined the role of radio frequency ablation in the treatment of renal cell carcinoma.MATERIALS AND METHODS: A total of 16 patients with biopsy proven renal cell carcinoma were treated with radio frequency ablation in an outpatient setting and followed for a minimum of 4 years.RESULTS: Of the 16 patients 5 died before", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15947578", "endSection": "abstract" }, { "offsetInBeginSection": 1606, "offsetInEndSection": 1864, "text": "ence, pain relief was noted to occur very rapidly in 100% of cases. In agreement with the literature data, our results show that CT-guided percutaneous radio-frequency ablation can actually replace operative excision in the treatment of osteoid osteoma as it", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11779979", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1450, "text": "hanced T1-weighted images. The sequential MR imaging showed the radio frequency lesions decreased in volume in all cases, suggesting focal control.CONCLUSION: Stereotactic MR-guided radio frequency brain tumor ablation is a feasible and promising technique that can be an attrac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7900601", "endSection": "abstract" }, { "offsetInBeginSection": 1646, "offsetInEndSection": 1853, "text": "These results suggest radio-frequency energy is a seductive alternative to direct current ablation for percutaneous modification of atrioventricular conduction in patients with refractory atrial arrhythmias.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1417404", "endSection": "abstract" }, { "offsetInBeginSection": 1338, "offsetInEndSection": 1797, "text": " 89.7% (95% CI 78.5-97.9), respectively. The percent decrease in the glomerular filtration rate was significantly lower in the radio frequency ablation group at early and last followup.CONCLUSIONS: In appropriately selected patients with stage cT1b renal cell carcinoma radio frequency ablation is an effective treatment option that provides 5-year overall, cancer specific and disease-free survival comparable to that of partial nephrectomy as well as better", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25106899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "OBJECTIVE: To explore the clinical value of CT guided radio frequency ablation in the treatment of pelvis tumor.METHODS: 11 males and 8 females ranging from 25 to 49 years old (average 37) were enrolled in this study, all the 19 patients were suffering from pelvis tumor including giant cell tumor of bone (2/19), Ewing's sarcoma (2/19), malignant fibrous histiocytoma (3/19) and metastat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20017327", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1264, "text": "In patients with metastatic disease, RF ablation may be suitable for treatment of a small tumor burden or for palliation of larger tumors that cause symptoms such as cough, hemoptysis, or pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12376615", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 1070, "text": "In patients with non-small cell lung malignancy who are not candidates for surgery owing to poor cardiorespiratory reserve, RF ablation alone or followed by conventional radiation therapy with or without chemotherapy may prove to be a treatment option.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12376615", "endSection": "abstract" } ] }, { "body": "What does \"28\" stand for in the Disease Activity Score DAS28?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25173347", "http://www.ncbi.nlm.nih.gov/pubmed/23378146", "http://www.ncbi.nlm.nih.gov/pubmed/28089983", "http://www.ncbi.nlm.nih.gov/pubmed/32427982", "http://www.ncbi.nlm.nih.gov/pubmed/25600850", "http://www.ncbi.nlm.nih.gov/pubmed/26449852", "http://www.ncbi.nlm.nih.gov/pubmed/21748861", "http://www.ncbi.nlm.nih.gov/pubmed/17330303", "http://www.ncbi.nlm.nih.gov/pubmed/19772784", "http://www.ncbi.nlm.nih.gov/pubmed/24339425", "http://www.ncbi.nlm.nih.gov/pubmed/30402934", "http://www.ncbi.nlm.nih.gov/pubmed/31590930", "http://www.ncbi.nlm.nih.gov/pubmed/32669456", "http://www.ncbi.nlm.nih.gov/pubmed/29578196", "http://www.ncbi.nlm.nih.gov/pubmed/16978395", "http://www.ncbi.nlm.nih.gov/pubmed/28676129", "http://www.ncbi.nlm.nih.gov/pubmed/32475078", "http://www.ncbi.nlm.nih.gov/pubmed/21204103", "http://www.ncbi.nlm.nih.gov/pubmed/30368562", "http://www.ncbi.nlm.nih.gov/pubmed/15901635", "http://www.ncbi.nlm.nih.gov/pubmed/24955759", "http://www.ncbi.nlm.nih.gov/pubmed/23950187", "http://www.ncbi.nlm.nih.gov/pubmed/24599677", "http://www.ncbi.nlm.nih.gov/pubmed/19849865", "http://www.ncbi.nlm.nih.gov/pubmed/30168272", "http://www.ncbi.nlm.nih.gov/pubmed/23818710", "http://www.ncbi.nlm.nih.gov/pubmed/19635732", "http://www.ncbi.nlm.nih.gov/pubmed/20459619", "http://www.ncbi.nlm.nih.gov/pubmed/29955927", "http://www.ncbi.nlm.nih.gov/pubmed/17611990", "http://www.ncbi.nlm.nih.gov/pubmed/25530992", "http://www.ncbi.nlm.nih.gov/pubmed/27870649", "http://www.ncbi.nlm.nih.gov/pubmed/25031546", "http://www.ncbi.nlm.nih.gov/pubmed/26414115", "http://www.ncbi.nlm.nih.gov/pubmed/25143522", "http://www.ncbi.nlm.nih.gov/pubmed/26200604", "http://www.ncbi.nlm.nih.gov/pubmed/24983407", "http://www.ncbi.nlm.nih.gov/pubmed/22673898" ], "ideal_answer": [ "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s basically a measure of how active a patient is in regards to how active they are in relation to the DAS28. The 28 joint DAS (28 joints) is a way to measure how active the patient is compared to other people with the same disease.", "DAS28 is a subjective Disease Activity Score in Rheumatoid Arthritis patients that checks 28 individual joints.", " In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting. The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients.", "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s a measure of how active a patient is in regards to how active they are in relation to the DAS28. The 28 joint DAS (28 joints) is the highest score.", "In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting.", "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s basically a measure of how active a patient is in regards to how active they are in relation to the DAS28. The 28 joint DAS (28 joints) is a way to measure how active the patient is compared to other patients with the same disease.", "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s a measure of how active a patient is in regards to how active they are in relation to the DAS28." ], "exact_answer": [ "28 joints" ], "type": "factoid", "id": "5fe3130da43ad3127800003f", "snippets": [ { "offsetInBeginSection": 159, "offsetInEndSection": 400, "text": " In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24599677", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 194, "text": "The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25173347", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 359, "text": "the disease activity score with 28 joint counts with erythrocyte sedimentation rate (DAS28) remission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24983407", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 137, "text": "Disease activity score in 28 joints (DAS28)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676129", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 1029, "text": "DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30368562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "The subjective components of the Disease Activity Score 28-joints (DAS28) in rheumatoid arthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29955927", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "To determine the contribution of fibromyalgia (FM) to the subjective components of the Disease Activity Score 28-joints (DAS28) in patients with rheumatoid arthritis (RA), and to analyse the discriminatory performance of the derived DAS28 patient-reported components (DAS28-P) to identify patients with fibromyalgic RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29955927", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 1001, "text": "Analysis of disease activity scores (DAS28 [disease activity score based on the 28-joint count]) over time showed that, after the initial rapid improvement during the first 6 to 22 weeks of therapy, a further decrease in disease activity of 0.2 units in the DAS28 score per year was observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16978395", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 581, "text": "ceiver operating characteristic (ROC) curves analysis allowed to obtain optimal cut-off predictors of a 28-joint disease activity score (DAS28) < or =2.85. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19635732", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 424, "text": "We hypothesize that augmented pain processing, fibromyalgic features, poorer mental health, and patient-reported 28-joint disease activity score (DAS28) components are associated in RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25600850", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 884, "text": "ter 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20459619", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 752, "text": "diographs of hands and feet, pain, and the modified 28 joint disease activity score (DAS28) were also assessed.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15901635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: Disease Activity Score in 28 Joints (DAS28) is a scoring system to evaluate disease activity and treatment response in rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27870649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "OBJECTIVE: Antirheumatic treatment is frequently not appropriately modified, according to American College of Rheumatology guidelines, in patients with active rheumatoid arthritis (RA) as defined by a Disease Activity Score in 28 joints (DAS28) score greater tha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21748861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been increasingly used in clinical practice and research studies of rheumatoid arthr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23950187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been widely used in clinical practice and research studies of rheumatoid arthr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26200604", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "OBJECTIVE: The Disease Activity Score in 28 joints (DAS28), used to assess disease activity in rheumatoid arthritis (RA), is a composite score comprising clinical, biochemical, and patient self-report mea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24339425", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "OBJECTIVE: To determine whether using a reweighted disease activity score that better reflects joint synovitis, i.e., the 2-component Disease Activity Score in 28 joints (DAS28) (based on swollen joint count and C-reactive protein level), produces more clinically relevant treatment outcome trajectories compared to the standard 4-component ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32475078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "OBJECTIVE: Ankle joints are frequently neglected in activity scoring systems, including the Disease Activity Score in 28 join", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26414115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "OBJECTIVE: The Disease Activity Score in 28 joints (DAS28) is a key measure in clinical practice and clinic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378146", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 275, "text": " most widely used one is the Disease Activity Score involving 28 joint counts (DAS28) for which cut-offs were proposed to help physicians classify patients. How", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25031546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "BACKGROUND: Disease Activity Score in 28 Joints (DAS28) is a scoring system to evaluate disease activity and treatment response in rheumatoid arth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27870649", "endSection": "abstract" }, { "offsetInBeginSection": 275, "offsetInEndSection": 597, "text": "METHODS: Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23818710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "INTRODUCTION: The aim of this study was to determine a low disease activity threshold--a 28-joint disease activity score (DAS28) value--for the decision to maintain unchanged disease-modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis patients, based on expert opinion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19849865", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Comparison of Disease Activity Score in 28 joints with ESR (DAS28), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) & Routine Assessment of Patient Index Data with 3 measures (RAPID3) for assessing disease activity in patients with rheumatoid arthritis at initial presentation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29578196", "endSection": "title" }, { "offsetInBeginSection": 113, "offsetInEndSection": 460, "text": "We assessed achievement of remission as defined by Boolean criteria, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) and determined the components that limit patients in SDAI, CDAI, or DAS28(CRP) remission from achieving Boolean remission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31590930", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 512, "text": "METHODS: Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21204103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "OBJECTIVE: We used the 28-joint Disease Activity Score (DAS28) and the European League Against Rheumatism Sj\u00f6gren's Syndrome Disease Activity Index (ESSDAI) articular domain to assess the effect of rituximab (RTX) and abatacept (ABA) on articular involvement in primary Sj\u00f6gren syndrome (pSS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28089983", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 455, "text": "METHOD: The clinical data of 189 consecutive RA patients, including RAPID3 questionnaire, Disease Activity Score based on 28-joint count (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI), and ultrasonography of hand and wrist joints were collected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30402934", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 388, "text": "Disease activity score in 28 joints (DAS28)-remission has not been included among American College of Rheumatology/European League Against Rheumatism definitions, because of its association with significant residual disease activity, partly due to high weighting of acute-phase reactants (APR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "OBJECTIVE: To examine the influence of components of the Disease Activity Score 28 (DAS28) [tender joint count (TJC), swollen joint count (SJC), patient's general health (GH), and erythrocyte sedimentation rate (ESR)] on the total DAS28 score, and overlapping of the 4 individual components in rheumatoid arthritis (RA) patients with low, moderate, or high disease activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17611990", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 388, "text": "This study investigates if, and to what extent, non-adherence to treatment would lead to a higher 28-joint count disease activity score (DAS28) in the first year after diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26449852", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 750, "text": "Radiographs of hands and feet, pain, and the modified 28 joint disease activity score (DAS28) were also assessed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15901635", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 389, "text": "Tender-/swollen-joint count, Health Assessment Questionnaire Disability Index (HAQ-DI), Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI) and DAS28-monocyte chemotactic protein-1 (DAS28-MCP-1) scores were obtained every 3 months.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32427982", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 316, "text": "METHOD: All patients were na\u00efve to biological disease-modifying anti-rheumatic drugs (bDMARDs) and in low or moderate Disease Activity Score of 28 joints with C-reactive protein (DAS)28-CRP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30168272", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 640, "text": "We compared RA disease activity using 28-joint Disease Activity Score (DAS28) and its components, and EULAR response, between patients with and without AITD, using logistic regression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32669456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "BACKGROUND: Disease Activity Score in 28 Joints (DAS28) is a scoring system to evaluate disease activity and treatment response in rheumatoid art", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27870649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "BACKGROUND: The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint count (TJC28 and SJC28), a patient-reported measure for general health (GH), and an inflammatory marker (either the erythrocyte sedimentation rate [ESR] or the C-reactive protein [CRP]) into a composite measure of disease activity in rheumatoid art", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24955759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "OBJECTIVE: The Disease Activity Score in 28 joints (DAS28) is a key measure in clinical practice and clini", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23378146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "OBJECTIVE: The Disease Activity Score including 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI) were developed in order to provide a quantifiable measure of rheumatoid arthritis (RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19772784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been increasingly used in clinical practice and research studies of rheumatoid arth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23950187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "OBJECTIVES: To evaluate the application of Disease Activity Score 28 (DAS28) to assess joint involvement in Systemic Lupus Erythematosus (SLE).METHODS: Sixty-nine SLE patients, complaining of joint symptoms, and 44 rheumatoid arthritis (RA) pa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25530992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 640, "text": "OBJECTIVE: To examine the influence of components of the Disease Activity Score 28 (DAS28) [tender joint count (TJC), swollen joint count (SJC), patient's general health (GH), and erythrocyte sedimentation rate (ESR)] on the total DAS28 score, and overlapping of the 4 individual components in rheumatoid arthritis (RA) patients with low, moderate, or high disease activity.METHODS: The effect of each component was studied in the FIN-RACo trial patients at 6 months and in a \"theoretical model,\" where each component of the DAS28 ranged as follows: TJC and SJC from 0 to 28, GH from 0 to 100, and ESR from 1 to 100, while the other 3 compo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17611990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "OBJECTIVE: To assess the factorial structure of the Disease Activity Score including a 28-joint count (DAS28) if applied in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).METHODS: DAS28 values from 85 consecutive PsA outpatients and 2 RA patient cohorts comprising 85 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17330303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Disease activity assessment of rheumatoid arthritis in daily practice: validity, internal consistency, reliability and congruency of the Disease Activity Score including 28 joints (DAS28) compared with the Clinical Disease Activity Index (CDAI).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19772784", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "OBJECTIVES: Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) is used instead of erythrocyte sedimentation rate (DAS28-ESR) to assess rheumatoid arthritis disease activity; however, values for remission and low disease activity (LDA) for DAS28-CRP have not bee", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25143522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "OBJECTIVE: To optimize use of the Disease Activity Score in 28 joints (DAS28) in early rheumatoid arthritis (RA) by adding the \"squeeze test\" of forefeet.METHODS: The squeeze test is used to examine bilateral compression pain (BCP) across the metatarsophal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22673898", "endSection": "abstract" } ] }, { "body": "What is EPICCURE?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32728595" ], "ideal_answer": [ "EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30%-50%) undergoing elective coronary artery bypass surgery. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887)." ], "type": "summary", "id": "602c19f11cb411341a00011b", "snippets": [ { "offsetInBeginSection": 553, "offsetInEndSection": 796, "text": "EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30%-50%) undergoing elective coronary artery bypass surgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32728595", "endSection": "abstract" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1568, "text": "EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32728595", "endSection": "abstract" } ] }, { "body": "List updates for JASPAR 2020", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31701148" ], "ideal_answer": [ "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles.", "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, a Q&A forum was created to ease the communication between the user community and JASPAR curators. Finally, the genomic tracks, inference tool, and TF-binding profile similarity clusters were updated.", "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles.", "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release.", "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature." ], "exact_answer": [ [ "245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi)" ], [ "156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects)" ], [ "A novel collection of unvalidated TF-binding profiles for which curators did not find orthogonal supporting evidence in the literature was added" ], [ "Dedicated web form to engage the community in the curation of unvalidated TF-binding profiles" ], [ "A Q&A forum was created to ease the communication between the user community and JASPAR curators" ], [ "The genomic tracks, inference tool, and TF-binding profile similarity clusters were updated" ] ], "type": "list", "id": "60296ace1cb411341a000115", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1190, "text": "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, we created a Q&A forum to ease the communication between the user community and JASPAR curators. Finally, we updated the genomic tracks, inference tool, and TF-binding profile similarity clusters. All the data is available through the JASPAR website, its associated RESTful API, and through the JASPAR2020 R/Bioconductor package.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31701148", "endSection": "abstract" } ] }, { "body": "Was golimumab tested for diabetes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33207093" ], "ideal_answer": [ "Yes, among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo." ], "exact_answer": "yes", "type": "yesno", "id": "601c46f61cb411341a00001d", "snippets": [ { "offsetInBeginSection": 2481, "offsetInEndSection": 2674, "text": "CONCLUSIONS: Among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33207093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33207093", "endSection": "title" }, { "offsetInBeginSection": 450, "offsetInEndSection": 737, "text": "lticenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33207093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33207093", "endSection": "title" } ] }, { "body": "Is G3BP1 found in stress granules?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31956030", "http://www.ncbi.nlm.nih.gov/pubmed/31704836", "http://www.ncbi.nlm.nih.gov/pubmed/29463567" ], "ideal_answer": [ "Yes,\nRAS GTPase-activating protein-binding protein (G3BP1) is an RNA-binding protein that is essential for assembling stress granules." ], "exact_answer": "yes", "type": "yesno", "id": "604fc22894d57fd879000008", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 142, "text": "RAS GTPase-activating protein-binding protein (G3BP1) is an RNA-binding protein that is essential for assembling stress granules. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31704836", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 749, "text": "Within SGs, single-molecule localization microscopy revealed distributed hotspots of immobilized G3BP1 and IMP1 that reflect the presence of relatively immobile nanometer-sized nanocores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29463567", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 698, "text": "Using super-resolution and expansion microscopy, we find that the SG component UBAP2L [11, 12] and the core protein G3BP1 [5, 11-13] occupy different domains inside SGs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31956030", "endSection": "abstract" } ] }, { "body": "What is Progeria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30548460", "http://www.ncbi.nlm.nih.gov/pubmed/1791375", "http://www.ncbi.nlm.nih.gov/pubmed/32799251", "http://www.ncbi.nlm.nih.gov/pubmed/3736130", "http://www.ncbi.nlm.nih.gov/pubmed/27931782", "http://www.ncbi.nlm.nih.gov/pubmed/25027075", "http://www.ncbi.nlm.nih.gov/pubmed/32046343", "http://www.ncbi.nlm.nih.gov/pubmed/22752073", "http://www.ncbi.nlm.nih.gov/pubmed/27267192", "http://www.ncbi.nlm.nih.gov/pubmed/29127216", "http://www.ncbi.nlm.nih.gov/pubmed/8471783", "http://www.ncbi.nlm.nih.gov/pubmed/31834988", "http://www.ncbi.nlm.nih.gov/pubmed/19823665", "http://www.ncbi.nlm.nih.gov/pubmed/17664768", "http://www.ncbi.nlm.nih.gov/pubmed/8459803", "http://www.ncbi.nlm.nih.gov/pubmed/31014187", "http://www.ncbi.nlm.nih.gov/pubmed/16429102", "http://www.ncbi.nlm.nih.gov/pubmed/18769635", "http://www.ncbi.nlm.nih.gov/pubmed/23666920", "http://www.ncbi.nlm.nih.gov/pubmed/1590260", "http://www.ncbi.nlm.nih.gov/pubmed/14582653", "http://www.ncbi.nlm.nih.gov/pubmed/21251803", "http://www.ncbi.nlm.nih.gov/pubmed/22121285", "http://www.ncbi.nlm.nih.gov/pubmed/24122691", "http://www.ncbi.nlm.nih.gov/pubmed/33087645" ], "ideal_answer": [ "Hutchinson-Gilford progeria syndrome is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction.", "Progeria is a rare genetic premature ageing disorder.", "Progeria is a rare genetic disorder that causes premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke).", "Progeria is a rare genetic disorder, characterized by premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke).", "Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C . In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24 .", "Hirschford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction.", "Progeria is a rare genetic disorder, characterized by progressive premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke).", "Progeria is a genetic disorder that causes premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke).", "Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction" ], "type": "summary", "id": "601d725d1cb411341a000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32046343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Hutchinson Gilford progeria syndrome (HGPS) is a devastating accelerated aging disease caused by LMNA gene mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31834988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Hutchinson-Gilford progeria syndrome is a rare genetic disorder, characterized by progressive premature aging and early death in the first or second decade of life, usually secondary to cardiovascular events (myocardial infarction and stroke).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31014187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30548460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23666920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "BACKGROUND: Progeria is a rare segmental premature aging disease with significant skeletal abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22752073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Progeria is a rare, genetically determined condition characterized by accelerated aging in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16429102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner sy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33087645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Patie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27931782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Werner's syndrome (adult progeria) is a rare autosomal recessive condition characterized mainly by a characteristic habitus (short stature, light body weight) scleroderma like changes of the limbs and premature aging. Chronic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1791375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The Hutchinson-Gilford syndrome or progeria is a rare autosomal dominant syndrome characterized by premature aging and involvement of internal systems, such as the circulatory and locomotor. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27267192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The glycosylation of proteins in fibroblasts from people with the premature ageing disease Hutchinson-Gilford Progeria Syndrome (progeria) was investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8459803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of \u223c1 in 18 million individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29127216", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "INTRODUCTION: Progeria also known as Hutchinson Gilford Progeria Syndrome (HGPS) (MIM176670) is a very uncommon fatal genetic untimely aging syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32799251", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Hutchinson-Gilford progeria syndrome (HGPS), a rare disease that results in what appears to be premature aging, is caused by the production of a mutant form of prelamin A known as progerin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18769635", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 292, "text": "Although children with progeria have the appearance of premature aging or senility, the term is misleading because reported cases of progeria have not manifested most physical or biochemical aspects of old age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8471783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The Hutchinson-Gilford syndrome or progeria is a rare autosomal dominant syndrome characterized by premature aging and involvement of internal systems, such as the circulatory and locomotor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27267192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The basic genetic defect in the Hutchinson-Gilford Progeria Syndrome (progeria), a premature aging syndrome, is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3736130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Progeria: a rare genetic premature ageing disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25027075", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Progeria is characterized by clinical features that mimic premature ageing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25027075", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 119, "text": "Progeria is a rare fatal genetic condition characterized by an appearance of accelerated aging in children.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24122691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Progeria is a rare and peculiar combination of dwarfism and premature aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19823665", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 379, "text": "Progeria is a rare autosomal dominant genetic disorder of premature aging characterized by marked growth retardation and specific, progressive, premature senescent changes of the skin and other tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14582653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Progeria is an autosomal dominant, premature aging syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Progeria is a rare genetic disease with striking features that resemble accelerated aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1590260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Progeria, also known as Hutchinson-Gilford syndrome, is an extremely rare, severe genetic condition wherein symptoms resembling aspects of aging are manifested at an early age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22121285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Progeria: a human-disease model of accelerated aging.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1590260", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Progeria, or Hutchinson-Gilford syndrome, is a rare genetic disease, characterized by several clinical features that develop in childhood, in particular, an accelerated aging aspect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21251803", "endSection": "abstract" } ] }, { "body": "Describe CrossICC", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32978617" ], "ideal_answer": [ "CrossICC is an R package designed for the unsupervised clustering of gene expression data from multiple datasets/platforms without the requirement of batch effect adjustment. CrossICC utilizes an iterative strategy to derive the optimal gene signature and cluster numbers from a consensus similarity matrix generated by consensus clustering.", "CrossICC is an R package designed for the unsupervised clustering of gene expression data from multiple datasets/platforms without the requirement of batch effect adjustment. CrossICC utilizes an iterative strategy to derive the optimal gene signature and cluster numbers from a consensus similarity matrix generated by consensus clustering. The package also provides abundant functions to visualize the identified subtypes and evaluate subtyping performance. The package is implemented in R and available at GitHub (https://github.com/bioinformatist/CrossICC) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/CrossICC.html) under the GPL v3 License." ], "type": "summary", "id": "60606c9994d57fd87900003b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "CrossICC: iterative consensus clustering of cross-platform gene expression data without adjusting batch effect.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32978617", "endSection": "title" }, { "offsetInBeginSection": 380, "offsetInEndSection": 1249, "text": " CrossICC is an R package designed for the unsupervised clustering of gene expression data from multiple datasets/platforms without the requirement of batch effect adjustment. CrossICC utilizes an iterative strategy to derive the optimal gene signature and cluster numbers from a consensus similarity matrix generated by consensus clustering. This package also provides abundant functions to visualize the identified subtypes and evaluate subtyping performance. We expected that CrossICC could be used to discover the robust cancer subtypes with significant translational implications in personalized care for cancer patients.AVAILABILITY AND IMPLEMENTATION: The package is implemented in R and available at GitHub (https://github.com/bioinformatist/CrossICC) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/CrossICC.html) under the GPL v3 License.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32978617", "endSection": "abstract" } ] }, { "body": "Which receptor is blocked by Finerenone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28025025", "http://www.ncbi.nlm.nih.gov/pubmed/32088716", "http://www.ncbi.nlm.nih.gov/pubmed/28926607", "http://www.ncbi.nlm.nih.gov/pubmed/30171161", "http://www.ncbi.nlm.nih.gov/pubmed/30356804", "http://www.ncbi.nlm.nih.gov/pubmed/26203193", "http://www.ncbi.nlm.nih.gov/pubmed/26634965", "http://www.ncbi.nlm.nih.gov/pubmed/29437893", "http://www.ncbi.nlm.nih.gov/pubmed/29779093", "http://www.ncbi.nlm.nih.gov/pubmed/31665733", "http://www.ncbi.nlm.nih.gov/pubmed/32945624", "http://www.ncbi.nlm.nih.gov/pubmed/28320854", "http://www.ncbi.nlm.nih.gov/pubmed/32910349", "http://www.ncbi.nlm.nih.gov/pubmed/26325557", "http://www.ncbi.nlm.nih.gov/pubmed/29668577", "http://www.ncbi.nlm.nih.gov/pubmed/33099609", "http://www.ncbi.nlm.nih.gov/pubmed/30825073", "http://www.ncbi.nlm.nih.gov/pubmed/26902493", "http://www.ncbi.nlm.nih.gov/pubmed/33179798", "http://www.ncbi.nlm.nih.gov/pubmed/31583611", "http://www.ncbi.nlm.nih.gov/pubmed/33107592", "http://www.ncbi.nlm.nih.gov/pubmed/31283930", "http://www.ncbi.nlm.nih.gov/pubmed/24621652", "http://www.ncbi.nlm.nih.gov/pubmed/25678098", "http://www.ncbi.nlm.nih.gov/pubmed/28577743", "http://www.ncbi.nlm.nih.gov/pubmed/26095025", "http://www.ncbi.nlm.nih.gov/pubmed/27431783", "http://www.ncbi.nlm.nih.gov/pubmed/32890415", "http://www.ncbi.nlm.nih.gov/pubmed/32729974", "http://www.ncbi.nlm.nih.gov/pubmed/31655812" ], "ideal_answer": [ "Finerenone is a nonsteroidal mineralocorticoid receptor antagonist." ], "exact_answer": [ "mineralocorticoid" ], "type": "factoid", "id": "601c3fc21cb411341a000019", "snippets": [ { "offsetInBeginSection": 242, "offsetInEndSection": 543, "text": "Finerenone (FIN), a novel, nonsteroidal, potent, and selective mineralocorticoid receptor antagonist, improves endothelial dysfunction through enhancing nitric oxide (NO) bioavailability and decreasing superoxide anion levels due to an upregulation in vascular and renal superoxide dismutase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32088716", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 589, "text": "Here, we investigated metabolic effects of the novel non-steroidal MRA finerenone (FIN) in a mouse model of high-fat diet (HFD)-induced obesity and the signaling pathways activated by MR antagonism at level of interscapular brown adipose tissue (iBAT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32729974", "endSection": "abstract" }, { "offsetInBeginSection": 460, "offsetInEndSection": 1102, "text": "OBJECTIVES: To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33107592", "endSection": "abstract" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1022, "text": "For example, the novel nonsteroidal MRA finerenone has a balanced distribution between the heart and kidney compared with spironolactone, which is preferentially concentrated in the kidneys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33099609", "endSection": "abstract" }, { "offsetInBeginSection": 834, "offsetInEndSection": 1026, "text": "Other nonsteroidal MRA such as apararenone, finerenone, AZD9977, and LY2623091 are in different clinical trials in patients with hypertension suffering from renal or hepatic fibrotic diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33179798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "(-)-Finerenone is a nonsteroidal mineralocorticoid receptor antagonist currently in phase III clinical trials for the treatment of chronic kidney disease in type 2 diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32890415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Mineralocorticoid Receptor Antagonists: a Comprehensive Review of Finerenone.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32910349", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "PURPOSE OF REVIEW: We aim to review the mechanism of action and safety profile of mineralocorticoid receptor antagonists (MRAs) and discuss the differences between selective and non-selective MRAs. More specifically, finerenone is a new medication that is currently under investigation for its promising cardiovascular and nephrological effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32910349", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1148, "text": " A new selective MRA named finerenone (originally BAY 94-8862) has shown promising results in several trials (ARTS-HF and ARTS-DN) and smaller studies. Finerenone may have a dose-dependent benefit over older MRAs, decreasing rates of albuminuria and levels of BNP and NT-ProBNP without causing a significant increase in serum potassium levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32910349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Mineralocorticoid receptor antagonism by finerenone is sufficient to improve function in preclinical muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32945624", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The non-steroidal mineralocorticoid receptor antagonist finerenone prevents cardiac fibrotic remodeling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31283930", "endSection": "title" }, { "offsetInBeginSection": 241, "offsetInEndSection": 453, "text": "A mouse model of cardiac fibrosis induced by short-term isoproterenol injection was used to compare the nonsteroidal MRA finerenone and the steroidal MRA eplerenone in equi-efficient systemic MR blocking dosages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29437893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Finerenone is a novel selective nonsteroidal mineralocorticoid receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28577743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "BACKGROUND AND OBJECTIVES: Finerenone is a selective, non-steroidal mineralocorticoid receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29779093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND AND OBJECTIVES: Finerenone\u00a0(BAY 94-8862) is a selective, nonsteroidal mineralocorticoid receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30825073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24621652", "endSection": "title" }, { "offsetInBeginSection": 170, "offsetInEndSection": 416, "text": "isease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalem", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31655812", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 429, "text": "disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkale", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31665733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "AIMS: Finerenone (BAY 94-8862) is a novel non-steroidal mineralocorticoid receptor antago", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28025025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND: Finerenone (BAY\u00a094-8862) is a potent non-steroidal, selective mineralocorticoid receptor antagonist being developed for the treatment of patients with type\u00a02 diabetes and chronic kidne", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "BACKGROUND: The novel nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone holds promise to be safe and efficient in the treatment of patients with heart failure and/or chronic kidn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28926607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "BACKGROUND: The non-steroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) has been used to treat chronic heart failure (CHF) with reduced ejection fraction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29668577", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 520, "text": "Finerenone, a novel nonsteroidal MR antagonist, is presently being evaluated in two clinical phase IIb trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26203193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Protects Against Acute Kidney Injury-Mediated Chronic Kidney Disease: Role of Oxidative Stress.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320854", "endSection": "title" }, { "offsetInBeginSection": 110, "offsetInEndSection": 341, "text": "Mineralocorticoid receptor antagonism has shown to be helpful against renal IR consequences; however, the potential benefit of novel nonsteroidal mineralocorticoid receptor antagonists such as finerenone has to be further explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28320854", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 441, "text": "The Munich Wistar Fr\u00f6mter (MWF) rat is a model of chronic kidney disease (CKD), which exhibits endothelial dysfunction associated to low nitric oxide availability. We hypothesize that the new highly selective, non-steroidal mineralocorticoid receptor (MR) antagonist, finerenone, reverses both endothelial dysfunction and microalbuminuria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30356804", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 556, "text": "OBJECTIVE: To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone, given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26325557", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 881, "text": "Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MR(SMKO)) and mice treated with the MR antagonist finerenone (MI-fine) had improved left ventricular compliance and elastance when compared with infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, mL mg(-1) min(-1): MI-CTL: 1.1 \u00b1 0.5, nonsignificant; MI-MR(SMKO): 4.6 \u00b1 1.6 [P<0.05]; MI-fine: 3.6 \u00b1 0.7 [P<0.01]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26902493", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "AIMS: To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25678098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095025", "endSection": "title" }, { "offsetInBeginSection": 389, "offsetInEndSection": 572, "text": "Finerenone is a novel nonsteroidal MRA, with higher selectivity toward the mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding affinity than eplerenone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095025", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 653, "text": "Recently, finerenone (BAY 94-8862) has emerged as a next-generation non-steroidal dihydropyridine-based MR antagonist designed to minimize off-target effects while maintaining potent efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26634965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431783", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Finerenone (BAY 94-8862) is a nonsteroidal mineralocorticoid receptor antagonist in development for the treatment of diabetic kidney disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Biotransformation of Finerenone, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, in Dogs, Rats, and Humans, In Vivo and In Vitro", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30171161", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Mass balance and biotransformation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, were investigated in four healthy male volunteers following a single oral administration of 10 mg (78 \u03bcCi) of [14C]finerenone and compared with data from studies in dogs and rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30171161", "endSection": "abstract" } ] }, { "body": "Is colistin an antibiotic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33057672", "http://www.ncbi.nlm.nih.gov/pubmed/30892111", "http://www.ncbi.nlm.nih.gov/pubmed/30088449" ], "ideal_answer": [ "Yes,\ncolistin is an antibiotic." ], "exact_answer": "yes", "type": "yesno", "id": "6081af3c4e6a4cf630000008", "snippets": [ { "offsetInBeginSection": 493, "offsetInEndSection": 538, "text": "all antibiotics tested, apart from colistin, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33057672", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 1273, "text": "Among the selected antibiotics, there were 12 fluoroquinolone antibiotics (tosufloxacin, levofloxacin, sparfloxacin, clinafloxacin, pazufloxacin, gatifloxacin, enrofloxacin, lomefloxacin, norfloxacin, fleroxacin, flumequine, ciprofloxacin), 15 beta-lactam or cephalosporin antibiotics (cefmenoxime, cefotaxime, ceftizoxime, cefotiam, cefdinir, cefoperazone, cefpiramide, cefamandole, cefixime, ceftibuten, cefmetazole, cephalosporin C, aztreonam, piperacillintazobactam, mezlocillin), 3 tetracycline antibiotics (meclocycline, doxycycline, tetracycline), 2 membrane-acting agents (colistin and clofoctol),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30088449", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 403, "text": " Mice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96\u2009h.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30892111", "endSection": "abstract" } ] }, { "body": "Is Tocilizumab (Actemra) used to block/antagonize the IL-6 receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22870473", "http://www.ncbi.nlm.nih.gov/pubmed/20953198", "http://www.ncbi.nlm.nih.gov/pubmed/18071945", "http://www.ncbi.nlm.nih.gov/pubmed/33262810", "http://www.ncbi.nlm.nih.gov/pubmed/32365119", "http://www.ncbi.nlm.nih.gov/pubmed/31164961", "http://www.ncbi.nlm.nih.gov/pubmed/20402381", "http://www.ncbi.nlm.nih.gov/pubmed/31809899", "http://www.ncbi.nlm.nih.gov/pubmed/20065633", "http://www.ncbi.nlm.nih.gov/pubmed/29952844", "http://www.ncbi.nlm.nih.gov/pubmed/24155139", "http://www.ncbi.nlm.nih.gov/pubmed/23844337", "http://www.ncbi.nlm.nih.gov/pubmed/30021477", "http://www.ncbi.nlm.nih.gov/pubmed/19368420", "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "http://www.ncbi.nlm.nih.gov/pubmed/31796986", "http://www.ncbi.nlm.nih.gov/pubmed/33269653", "http://www.ncbi.nlm.nih.gov/pubmed/20305672", "http://www.ncbi.nlm.nih.gov/pubmed/28841363", "http://www.ncbi.nlm.nih.gov/pubmed/22334272", "http://www.ncbi.nlm.nih.gov/pubmed/33264466" ], "ideal_answer": [ "yes, tocilizumab (actemra) is used to block/antagonize the il-6 receptor.", "Yes. Tocilizumab (Actemra) is an anti-IL-6 receptor antagonist. It is a monoclonal antibody against the receptor.", "Tocilizumab is an IL-6 receptor antagonist.", "yes, tocilizumab (actemra) is an approved humanized monoclonal antibody that blocks the il-6 receptor." ], "exact_answer": "yes", "type": "yesno", "id": "602e84e61cb411341a000126", "snippets": [ { "offsetInBeginSection": 398, "offsetInEndSection": 673, "text": "Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33262810", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 773, "text": "Tocilizumab, an anti-IL-6 receptor antibody, and corticosteroids were initially used to treat the increase in acute inflammatory proteins and the anasarca, resulting in decreased cytokine levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33269653", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 776, "text": "Tocilizumab, a monoclonal antibody against the IL-6 receptor, was initiated at a dose of 8 mg/kg every 4 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29952844", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 548, "text": "we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31796986", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 302, "text": " Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31809899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19368420", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 442, "text": "To increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20953198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Tocilizumab (Actemra; Genentech, Inc) is the first biologic therapy targeting the cytokine interleukin 6 (IL-6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22334272", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1255, "text": "over, our findings showed that combination of tocilizumab (Actemra; Roche), an anti-IL-6R monoclonal antibody, with carboplatin synergistically inhibited growth and proliferation of the EOC cells and the most direct axis for IL-6 gene expression was NF-\u03baB pathway.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30021477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20065633", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 158, "text": "Tocilizumab (TCZ) is a compound that inhibits the IL-6 receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20402381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28841363", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 399, "text": "the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA. Although thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20305672", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 455, "text": "increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4). Studies usin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20953198", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 477, "text": " present study, we have shown that the humanized anti-IL-6 receptor tocilizumab (Actemra) is also a potent inhibitor of IL-8 in TNBC cells. Similar ef", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33264466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical. Tocili", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20065633", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 411, "text": "tory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23844337", "endSection": "abstract" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1891, "text": "These lines of evidence indicate that tocilizumab is able to bind to both sIL-6R and mIL-6R and to inhibit IL-6 binding to its receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and mIL-6R, but not block the signaling of other IL-6 family cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "title" }, { "offsetInBeginSection": 820, "offsetInEndSection": 981, "text": "In addition, tocilizumab had the ability to bind to human IL-6R expressing COS-7 cells and to suppress the growth of the IL-6-dependent myeloma cell line, KPMM2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "To characterize the biological activity of tocilizumab, a humanized anti-human interleukin-6 receptor (IL-6R) monoclonal antibody, we examined its binding activity to both soluble IL-6R (sIL-6R) and membrane bound IL-6R (mIL-6R) and its neutralizing activity to other IL-6 family cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "abstract" }, { "offsetInBeginSection": 1412, "offsetInEndSection": 1615, "text": "Tocilizumab inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by their corresponding cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 819, "text": "Moreover, tocilizumab suppressed the IL-6/sIL-6R complex-induced proliferation of human gp130-transfected cell, BAF-h130.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 624, "text": "In addition, tocilizumab had the ability to dissociate IL-6 and sIL-6R from their preformed complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 413, "text": "ELISA assay demonstrated that tocilizumab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose-dependent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102523", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 933, "text": "Tocilizumab recognizes both the membrane-bound and the soluble form IL-6R and specifically blocks IL-6 actions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18071945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Humanized antihuman IL-6 receptor antibody, tocilizumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18071945", "endSection": "title" }, { "offsetInBeginSection": 715, "offsetInEndSection": 821, "text": "Tocilizumab is a humanized antihuman IL-6 receptor antibody designed using genetic engineering technology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18071945", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1163, "text": "Tocilizumab is expected to ameliorate the autoimmune inflammatory diseases with IL-6 overproduction and has been clinically developed as a therapeutic agent for RA, systemic-onset and articular types of JIA, Crohn's disease, etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18071945", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 486, "text": "Tocilizumab/Actemra is an anti-IL-6R antibody, which can competitively block IL-6 binding to the IL-6R.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31164961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Tocilizumab (TCZ; RoActemra\u00ae or Actemra\u00ae) is a recombinant humanized monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870473", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 386, "text": "In 2009 the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20305672", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 309, "text": "Tocilizumab binds to the interleukin-6 receptor (IL-6R) and thereby blocks signaling of the pro-inflammatory cytokine IL-6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32365119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Tocilizumab (RoActemra(\u00ae); Actemra(\u00ae)) is a recombinant humanized monoclonal antibody that acts as an interleukin-6 receptor antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155139", "endSection": "abstract" } ] }, { "body": "Is the process of DNA loop-extrusion independent of ATP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29706548", "http://www.ncbi.nlm.nih.gov/pubmed/29754816", "http://www.ncbi.nlm.nih.gov/pubmed/29300120", "http://www.ncbi.nlm.nih.gov/pubmed/31780627", "http://www.ncbi.nlm.nih.gov/pubmed/16292342", "http://www.ncbi.nlm.nih.gov/pubmed/27224481", "http://www.ncbi.nlm.nih.gov/pubmed/29079757", "http://www.ncbi.nlm.nih.gov/pubmed/29140466", "http://www.ncbi.nlm.nih.gov/pubmed/31753851", "http://www.ncbi.nlm.nih.gov/pubmed/27210764", "http://www.ncbi.nlm.nih.gov/pubmed/29472443", "http://www.ncbi.nlm.nih.gov/pubmed/30100265" ], "ideal_answer": [ "The process of DNA loop-extrusion is not independent of ATP. It is dependent on the energy of ATP hydrolysis.", "Yes, a single condensin complex is able to extrude tens of kilobase pairs of DNA, using the energy of ATP hydrolysis.", "The DNA-organizing mechanism of condensin depends on the energy of ATP hydrolysis but how this activity specifically promotes proper compaction and segregation of chromosomes during mitosis remains poorly understood." ], "exact_answer": "yes", "type": "yesno", "id": "5cebe41ea49efeb44c000006", "snippets": [ { "offsetInBeginSection": 110, "offsetInEndSection": 326, "text": "The DNA-organizing mechanism of condensin depends on the energy of ATP hydrolysis but how this activity specifically promotes proper compaction and segregation of chromosomes during mitosis remains poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29079757", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1037, "text": "We suggest that loading and translocation are mediated by conformational changes in cohesin's hinge driven by cycles of ATP hydrolysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29754816", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 316, "text": "Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706548", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 523, "text": "Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA.\u00a0", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706548", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 672, "text": "Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27210764", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 623, "text": "However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29300120", "endSection": "abstract" }, { "offsetInBeginSection": 321, "offsetInEndSection": 531, "text": "We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29472443", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 1081, "text": "Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29140466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Oligomerization and ATP stimulate condensin-mediated DNA compaction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29079757", "endSection": "title" }, { "offsetInBeginSection": 409, "offsetInEndSection": 522, "text": "Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29706548", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 537, "text": "DNA compaction by cohesin requires adenosine triphosphate (ATP) hydrolysis and is force sensitive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31780627", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 908, "text": "The identification and quantification of further initiation steps--ATP binding and extrusion of an initial DNA loop--allowed us to deduce a complete kinetic reinitiation scheme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16292342", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 520, "text": "In support of this model, single-molecule imaging experiments indicate that Saccharomyces cerevisiae condensin complexes can extrude DNA loops in an ATP-hydrolysis-dependent manner in\u00a0vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30100265", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 319, "text": "These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed to form loops by extrusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31753851", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 714, "text": "Loop formation and maintenance depend on cohesin's ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31753851", "endSection": "abstract" } ] }, { "body": "What is the effect of carbamazepine on CYP3A4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31650711" ], "ideal_answer": [ "Carbamazepine is an inducer of CYP3A4." ], "exact_answer": [ "Induces", "inducer", "induction" ], "type": "factoid", "id": "606ab57394d57fd87900004f", "snippets": [ { "offsetInBeginSection": 274, "offsetInEndSection": 379, "text": "Carbamazepine, a UGT and cytochrome P450 3A4 inducer, is a first-line treatment for trigeminal neuralgia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31650711", "endSection": "abstract" } ] }, { "body": "Is there an upper limit on the functional fraction of the human genome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28854598" ], "ideal_answer": [ "Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower.", "yes, there is an upper limit on the functional fraction of the human genome." ], "exact_answer": "yes", "type": "yesno", "id": "6060df1e94d57fd879000047", "snippets": [ { "offsetInBeginSection": 654, "offsetInEndSection": 815, "text": "Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28854598", "endSection": "abstract" } ] }, { "body": "What is Couvelaire Uterus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25102676", "http://www.ncbi.nlm.nih.gov/pubmed/9313351", "http://www.ncbi.nlm.nih.gov/pubmed/9788648", "http://www.ncbi.nlm.nih.gov/pubmed/15559411", "http://www.ncbi.nlm.nih.gov/pubmed/29233830", "http://www.ncbi.nlm.nih.gov/pubmed/28290978" ], "ideal_answer": [ "Couvelaire uterus is hematic infiltration uterine myometrium due to the formation of a massive hematoma. It is charecterised by dark purple patches with ecchymosis and indurations." ], "type": "summary", "id": "601c48c11cb411341a00001e", "snippets": [ { "offsetInBeginSection": 271, "offsetInEndSection": 394, "text": "Subsequent hysterotomy reveals Couvelaire uterus with major haemorrhage and requires subtotal hysterectomy for haemostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "A case of Couvelaire uterus with placenta accreta found during scheduled repeat low transverse Cesarean section will be discussed within this article. First described in the 1900s, Couvelaire syndrome, also known as uteroplacental apoplexy, is a rare form of nonfatal placenta abruption complication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28290978", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 849, "text": "Upon inspection, the uterus was found have dark purple patches with ecchymosis and indurations, diagnostic of Couvelaire uterus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28290978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Couvelaire uterus is rare in modern obstetrics, a state of the hematic infiltration uterine myometrium due to the formation of a massive hematoma retroplacental that can not be sold to the vaginal cavity through the cervical route. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102676", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 268, "text": "A Couvelaire uterus was diagnosed, showing typical blue-purple discolorations of the uterine wall, which are in fact haemorrhages caused by disseminated intravascular coagulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15559411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Couvelaire uterus is rare in modern obstetrics, a state of the hematic infiltration uterine myometrium due to the formation of a massive hematoma retroplacental that can not be sold to the vaginal cavity through the cervical route.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25102676", "endSection": "abstract" } ] }, { "body": "What protein is Otof gene encoding?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31875531", "http://www.ncbi.nlm.nih.gov/pubmed/32265471", "http://www.ncbi.nlm.nih.gov/pubmed/30509897", "http://www.ncbi.nlm.nih.gov/pubmed/32476384", "http://www.ncbi.nlm.nih.gov/pubmed/32106631", "http://www.ncbi.nlm.nih.gov/pubmed/33256196" ], "ideal_answer": [ "The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs)", "The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs). In the absence of otoferlin, signal transmission of IHCs fails due to impaired release of synaptic vesicles at the IHC synapse.", "The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs)." ], "exact_answer": [ "The OTOF gene encodes otoferlin" ], "type": "factoid", "id": "6080646c4e6a4cf630000004", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 323, "text": "Hereditary hearing loss is characterized by a very high genetic heterogeneity. The OTOF (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31875531", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Otoferlin (OTOF) gene mutations are the most common cause of hereditary ANSD according to investigations in several countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32476384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Different mutations of the OTOF gene, encoding for otoferlin protein expressed in the cochlear inner hair cells, induces a form of deafness that is the major cause of nonsyndromic recessive auditory neuropathy spectrum disorder in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32265471", "endSection": "abstract" }, { "offsetInBeginSection": 612, "offsetInEndSection": 690, "text": "Mutations in OTOF (otoferlin) can be the cause of nonsyndromic deafness DFNB9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32106631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs). In the absence of otoferlin, signal transmission of IHCs fails due to impaired release of synaptic vesicles at the IHC synapse. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33256196", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 185, "text": "Deafness DFNB9, caused by mutations in the OTOF gene encoding otoferlin, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30509897", "endSection": "abstract" } ] }, { "body": "What is hypercapnia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20181940", "http://www.ncbi.nlm.nih.gov/pubmed/31828519", "http://www.ncbi.nlm.nih.gov/pubmed/28779577", "http://www.ncbi.nlm.nih.gov/pubmed/21762783", "http://www.ncbi.nlm.nih.gov/pubmed/31811514", "http://www.ncbi.nlm.nih.gov/pubmed/27044749", "http://www.ncbi.nlm.nih.gov/pubmed/25895534", "http://www.ncbi.nlm.nih.gov/pubmed/23777386", "http://www.ncbi.nlm.nih.gov/pubmed/30202079", "http://www.ncbi.nlm.nih.gov/pubmed/26574187", "http://www.ncbi.nlm.nih.gov/pubmed/31844927", "http://www.ncbi.nlm.nih.gov/pubmed/32748016", "http://www.ncbi.nlm.nih.gov/pubmed/31264907", "http://www.ncbi.nlm.nih.gov/pubmed/32589951", "http://www.ncbi.nlm.nih.gov/pubmed/31484786" ], "ideal_answer": [ "Hypercapnia is also known as High CO2 retention." ], "type": "summary", "id": "604b6bec1cb411341a000170", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "High CO2 retention, or hypercapnia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31264907", "endSection": "abstract" }, { "offsetInBeginSection": 386, "offsetInEndSection": 613, "text": "Sixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO2) reduction after 6 months NIV,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31484786", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 496, "text": "Hypercapnia and respiratory acidosis are the main disadvantages of this ventilator strategy. The use of extracorporeal CO2 removal device has been introduced to support protective and ultra-protective ventilation during respiratory failure in complex cases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31828519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Hypercapnia has been reported to play an active role in protection against organ injury. The aim of this study was to determine whether a higher level of partial pressure of arterial carbon dioxide (PaCO2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31844927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Chronic obstructive pulmonary disease (COPD) exacerbation induces hypercapnic respiratory acidosis. Extracorporeal carbon dioxide removal (ECCO2R) aims to eliminate blood carbon dioxide (CO2) in order to reduce adverse effects from hypercapnia and the related acidosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31811514", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 844, "text": "was to examine the prevalence of day 1 and sustained (day 1 and 2) hypocapnia (Paco2\u00a0< 35\u00a0mm\u00a0Hg), normocapnia (Paco2 35-45\u00a0mm\u00a0Hg), and hypercapnia (Paco2 > 45\u00a0mm\u00a0Hg) in patients with ARDS. Secondary objectives included elucidating the effect of CO2 tension on ventilatory management and examining the r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589951", "endSection": "abstract" }, { "offsetInBeginSection": 838, "offsetInEndSection": 969, "text": "Normocapnia (82 measurements; 35 mmHg \u2264 PaCO2 < 45 mmHg) and hypercapnia groups (57 measurements; 45 mmHg \u2264 PaCO2) were classified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32748016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26574187", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Hypercapnia, the elevation of CO2 in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30202079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Hypercapnia, an elevation of the level of carbon dioxide (CO2) in blood and tissues, is a marker of poor prognosis in chronic obstructive pulmonary disease and other pulmonary disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23777386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Hypercapnia, the elevation of CO2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and it is associated with high mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25895534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Carbon dioxide (CO\u2082) retention, or hypercapnia, is a known risk of diving that can cause mental and physical impairments leading to life-threatening accidents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28779577", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 326, "text": "Hypoxia (low oxygen) and hypercapnia (high carbon dioxide) are co-incidental features of the tissue microenvironment in a range of pathophysiologic states, including acute and chronic respiratory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27044749", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Elevated blood and tissue CO(2), or hypercapnia, is common in severe lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20181940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "The effect of hypercapnia (an increase in CO(2) concentration in the blood) on the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) haemodynamic response has been well characterised and is commonly used for BOLD calibration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21762783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Hypercapnia in diving: a review of CO\u2082 retention in submersed exercise at depth.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28779577", "endSection": "title" } ] }, { "body": "What is TSA-Seq used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30154186" ], "ideal_answer": [ "TSA-Seq provides a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling.", "TSA-Seq is a new mapping method capable of providing a \"cytological ruler\" for estimating mean mean distance distances from nuclear speckles genome-wide and for predicting several MbP chromosome trajectories between nuclear compartments.", "TSA-Seq is used as a cytological ruler to calculate relative distances between nuclear elements in 3D genome organization maps.", "yes, tsa-seq is a new mapping method capable of providing a cytological ruler for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling.", "tsa-seq is a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling.", "we describe TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling" ], "type": "summary", "id": "5fe31318a43ad31278000045", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "title" }, { "offsetInBeginSection": 207, "offsetInEndSection": 496, "text": "we describe TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1251, "text": "Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for spatial organization of transcription and gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 497, "text": "In this study, we describe TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 502, "text": " this study, we describe TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ense", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30154186", "endSection": "abstract" } ] }, { "body": "Does the HercepTest use a polycloncal or monoclonal antibody?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22827758" ], "ideal_answer": [ "The HercepTest uses a polyclonal antibody." ], "exact_answer": [ "polyclonal" ], "type": "factoid", "id": "606c34c994d57fd879000077", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Comparison of HER2 immunohistochemical results using a monoclonal antibody (SV2-61\u03b3) and a polyclonal antibody (for Dako HercepTest) in advanced gastric cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22827758", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "We compared a monoclonal antibody (SV2-61\u03b3) and a polyclonal antibody (Dako HercepTest) in immunohistochemical assessments of human epidermal growth factor receptor 2 (HER2) expression in 73 samples of advanced gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22827758", "endSection": "abstract" } ] }, { "body": "Describe participants' experiences from the 100,000 genomes project", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30503854" ], "ideal_answer": [ "Interviewees' decisions to participate in 100\u202fkG\u202fP were based on interpersonal and institutional trust in the NHS, and on an investment in improving care for the future. Interviewees relied upon receiving good ongoing NHS care for managing their own or their child's rare disease, but they worried about what their relationships with NHS healthcare professionals would be like in future. A few participants worried about whether Genomics England's biorepository would remain protected and an asset of the NHS." ], "type": "summary", "id": "6027fa581cb411341a0000ee", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1222, "text": "In this paper, we present findings from a project involving 20 patients with rare diseases, or parents thereof, participating in the 100,000 genomes project (100\u202fkG\u202fP). We explored their experiences of, and views about, the project, including why they took part, and their hopes and concerns about the future of genomic medicine. Patients who attended genetic clinics for testing were offered the opportunity to undergo the more extensive whole genome sequencing (WGS) if they agreed to take part in the 100\u202fkG\u202fP. Once people had agreed, a specific additional appointment was organised for them. Taking part in the project therefore involved additional travel and appointments ('clinical labour'). We found that interviewees' decisions to participate in 100\u202fkG\u202fP were based on interpersonal and institutional trust in the NHS, and on an investment in improving care for the future. Interviewees relied upon receiving good ongoing NHS care for managing their own or their child's rare disease, but they worried about what their relationships with NHS healthcare professionals would be like in future. A few participants worried about whether Genomics England's biorepository would remain protected and an asset of the NHS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30503854", "endSection": "abstract" } ] }, { "body": "What is the role of elagolix in treatment of uterine fibroids?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30194661", "http://www.ncbi.nlm.nih.gov/pubmed/30570832", "http://www.ncbi.nlm.nih.gov/pubmed/30774352", "http://www.ncbi.nlm.nih.gov/pubmed/28579415", "http://www.ncbi.nlm.nih.gov/pubmed/31695514", "http://www.ncbi.nlm.nih.gov/pubmed/31650182", "http://www.ncbi.nlm.nih.gov/pubmed/33045114", "http://www.ncbi.nlm.nih.gov/pubmed/29476499", "http://www.ncbi.nlm.nih.gov/pubmed/32702363", "http://www.ncbi.nlm.nih.gov/pubmed/31971678" ], "ideal_answer": [ "Elagolix is approved for the treatment of moderate to severe pain caused by endometriosis. Elagolix is also effective for heavy bleeding caused by uterine fibroids." ], "type": "summary", "id": "6024a25c1cb411341a0000a1", "snippets": [ { "offsetInBeginSection": 1072, "offsetInEndSection": 1152, "text": "One of them, Elagolix, is in the early stages of testing in women with fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30774352", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1534, "text": "Recently, elagolix received US FDA approval for the treatment of moderate to severe pain caused by endometriosis. Several clinical trials assessed the efficacy of elagolix for the treatment of heavy bleeding caused by UFs and the definitive results of Phase III studies are expected. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31695514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "INTRODUCTION: Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29476499", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 388, "text": "In July 2018, the US FDA approved elagolix tablets for the management of moderate to severe pain associated with endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30194661", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 872, "text": "Elagolix with and without low-dose hormone add-back therapy is also undergoing phase III clinical development for heavy menstrual bleeding associated with uterine fibroids in the aforementioned locations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30194661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28579415", "endSection": "title" }, { "offsetInBeginSection": 1564, "offsetInEndSection": 1658, "text": "CONCLUSION(S): Elagolix significantly reduced heavy menstrual bleeding in women with fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28579415", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31971678", "endSection": "title" }, { "offsetInBeginSection": 1919, "offsetInEndSection": 2045, "text": "CONCLUSIONS: Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31971678", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1170, "text": "In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, treatment of premenopausal women with elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32702363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "CONTEXT: Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed for heavy menstrual bleeding associated with uterine fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31650182", "endSection": "abstract" }, { "offsetInBeginSection": 316, "offsetInEndSection": 486, "text": "Elagolix coadministered with estradiol/norethindrone acetate is in late-stage development for the management of heavy menstrual bleeding associated with uterine fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33045114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "CONTEXT: Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed for heavy menstrual bleeding associated with uterine fib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31650182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Elagolix is an oral gonadotropin-releasing hormone receptor antagonist indicated for the management of endometriosis-associated pain and in combination with estradiol/norethindrone acetate indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Ela", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33045114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "CONTEXT: Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed for heavy menstrual bleeding associated with uterine f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31650182", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1171, "text": "In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, treatment of premenopausal women with elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids.O", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32702363", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1732, "text": " ovulation. In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, treatment of premenopausal women with elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids.OBJECTIVE: This analysis aimed to evaluate the safety and efficacy of elagolix (300 mg twice a day) with add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate once a day) in reducing heavy menstrual bleeding associated with uterine fibroids in various subgroups of women over 6 months of treatment.STUDY DESIGN: Data were pooled from Elaris Uterine Fibroid-1 and Uterine Fibroid-2 studies, which evaluated premenopausal women (18-51 years) with heavy menstrual bleeding (>80 mL menstrual blood loss per cycle, alkaline hematin methodology) and ultrasound", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32702363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 837, "text": "CONTEXT: Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed for heavy menstrual bleeding associated with uterine fibroids.OBJECTIVE: The objective was to evaluate the effects of elagolix on ovulation and ovarian sex hormones.DESIGN AND SETTING: This was a randomized, open-label, multicenter study.PARTICIPANTS: Participants were healthy ovulatory women aged 18 to 40 years.INTERVENTIONS: Elagolix was administered orally for 3 continuous 28-day dosing intervals at 100 to 200 mg once daily (QD), 100 to 300 mg twice daily (BID), and 300 mg BID plus estradiol/norethindrone acetate (E2/NETA) 1/0.5 mg QD.MAIN OUTCOME MEASURES: The main outcomes measures were ovulation rates measured by transvaginal ultrasound, progesterone conce", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31650182", "endSection": "abstract" }, { "offsetInBeginSection": 1534, "offsetInEndSection": 1813, "text": "Available data on elagolix and UFs showed that the drug, with or without low-dose hormone add-back therapy, is able to significantly reduce menstrual blood loss, lead to amenorrhea and improve haemoglobin concentrations in the majority of participants in comparison with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31695514", "endSection": "abstract" } ] }, { "body": "Where is the organ of Corti located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32571852", "http://www.ncbi.nlm.nih.gov/pubmed/31939628", "http://www.ncbi.nlm.nih.gov/pubmed/32393641", "http://www.ncbi.nlm.nih.gov/pubmed/32154838", "http://www.ncbi.nlm.nih.gov/pubmed/32579963" ], "ideal_answer": [ "The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the cochlear spiral is the organ of Corti, a highly derived and rigorously patterned sensory epithelium that acts to convert auditory stimuli into neural impulses." ], "exact_answer": [ "In the inner ear" ], "type": "factoid", "id": "60805c344e6a4cf630000001", "snippets": [ { "offsetInBeginSection": 273, "offsetInEndSection": 436, "text": "We used mouse cochlear hair cells and House Ear Institute\u2011Organ of Corti\u00a01 (HEI\u2011OC1) cells to explore the relationship between mtDNA copy number and cell apoptosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31939628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "We study the vibration modes of a short section in the middle turn of the gerbil cochlea including both longitudinal and radial interstitial fluid spaces between the pillar cells and hair cells to determine the role of the interstitial fluid flow within the organ of Corti (OoC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32154838", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 179, "text": "The cochlear sensory epithelium, the organ of Corti, vibrates because of external and internal excitations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32579963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 323, "text": "The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the cochlear spiral is the organ of Corti, a highly derived and rigorously patterned sensory epithelium that acts to convert auditory stimuli into neural impulses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32571852", "endSection": "abstract" } ] }, { "body": "What eye disease(s) are associated with ocular toxoplasmosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31429610", "http://www.ncbi.nlm.nih.gov/pubmed/17596951", "http://www.ncbi.nlm.nih.gov/pubmed/30332547", "http://www.ncbi.nlm.nih.gov/pubmed/31589483", "http://www.ncbi.nlm.nih.gov/pubmed/15906073", "http://www.ncbi.nlm.nih.gov/pubmed/25127047", "http://www.ncbi.nlm.nih.gov/pubmed/33060522", "http://www.ncbi.nlm.nih.gov/pubmed/32068467" ], "ideal_answer": [ "Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis Infectious uveitis accounted for 37% of posterior uveitis cases of which toxoplasmosis was the most common cause. Toxoplasmosis was the most common cause of posterior uveitis (60%)", "A large percentage of posterior and infectious uveitis is associate with toxoplasmosis. Retinochoroiditis is associated with congenital toxoplasmosis.", "the most frequent manifestation of congenital toxoplasmosis is retinochoroiditis.", "Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis", "yes, ocular toxoplasmosis is associated with retinochoroiditis.", "Toxoplasmosis was the most common cause of posterior uveitis (60%) Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis Infectious uveitis accounted for 37% of posterior uveitis cases of which toxoplasmosis was the most common cause.", "The eye disease(s) associated with ocular toxoplasmosis are:1) ocular syphthalmia, 2) retinochoroiditis, 3) juvenile idiopathic arthritis and4) chorioretinitis.", "Toxoplasmosis was the most common cause of posterior uveitis (60%) for infectious uveritis, herpetic iridocyclitis, ocular toxoplasmosa, and bacterial endophthalmitis increased in patients with congenital tasma.", "Diseases associated with ocular toxoplasmosis are ocular syphilis, retinochoroiditis, juvenile idiopathic arthritis and chorioretinitis.", "Diseases associated with ocular toxoplasmosis are:1) ocular syphilis, 2) retinochoroiditis, 3) juvenile idiopathic arthritis and4) chorioretinitis.", "Ocular toxoplasmosis (OTS) is a rare but life threatening complication of ocular syphilis, which is followed by retinochoroiditis, juvenile idiopathic arthritis and chorioretinitis." ], "exact_answer": [ [ "retinochoroiditis" ], [ "posterior uveitis" ], [ "infectious uveitis" ] ], "type": "list", "id": "601d72181cb411341a000034", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 92, "text": "Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33060522", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 593, "text": "Infectious uveitis accounted for 37% of posterior uveitis cases of which toxoplasmosis was the most common cause. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30332547", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 881, "text": "Toxoplasmosis was the most common cause of posterior uveitis (60%)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31429610", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 703, "text": "For infectious uveitis, herpetic iridocyclitis, ocular toxoplasmosis, ocular syphilis, and bacterial endophthalmitis increased", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32068467", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 168, "text": "To evaluate quality of life in patients with uveitis-related to toxoplasmosis and its correlation with demographic, ocular involvement and psychosocial aspects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31589483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Retinal detachment associated with ocular toxoplasmosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127047", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "PURPOSE: To assess the frequency of retinal detachment (RD) and associated clinical features in ocular toxoplasmosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127047", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 274, "text": "Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects and congenital toxoplasmosis transmission was the first parasite to be linked to human lesions in the eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17596951", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 164, "text": "Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15906073", "endSection": "abstract" } ] }, { "body": "Which eukaryote genomes contain operons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "http://www.ncbi.nlm.nih.gov/pubmed/19740764", "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "http://www.ncbi.nlm.nih.gov/pubmed/17174523", "http://www.ncbi.nlm.nih.gov/pubmed/23668349", "http://www.ncbi.nlm.nih.gov/pubmed/18218978", "http://www.ncbi.nlm.nih.gov/pubmed/12949121", "http://www.ncbi.nlm.nih.gov/pubmed/24429814", "http://www.ncbi.nlm.nih.gov/pubmed/24931407" ], "ideal_answer": [ "Genes in nematode and ascidian genomes frequently occur in operons such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis We find that birth-death models of operon evolution reasonably describe the relative abundance of operons of different sizes in the C. elegans and Ciona genomes and generate predictions about the number of monocistronic, nonoperon genes that likely participate in the birth-death process", "The eukaryote genomes contain operons, which can be classified into boader families based, particularly, on the presence of other types of genes. Operons have been found to be present in the following genomes: caenorhabditis elegans, ciona, c. elegans, trichinella spiralis, trichuris muris and ciona intestinalis. Operons have also been reported to exist in the non-coding regions of the human and plant genomes.", "Genes in nematode and ascidian genomes frequently occur in operons. Such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis. The organization of genes into operons, clusters of genes that are co-transcribed to produce polycistronic pre-mRNAs, is a trait found in a wide range of eukaryotic groups, including multiple animal phyla.", "Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans", "Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans. Birth-death models of operon evolution reasonably describe the relative abundance of operons of different sizes in the C. elegans and Ciona genomes" ], "exact_answer": [ [ "C. elegans" ], [ "C. intestinalis" ], [ "C. briggsae" ], [ "C. remanei" ], [ "C. brenneri" ] ], "type": "list", "id": "5e9eaf3b0d431b5f73000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Genes in nematode and ascidian genomes frequently occur in operons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 258, "text": "such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1103, "text": "We find that birth-death models of operon evolution reasonably describe the relative abundance of operons of different sizes in the C. elegans and Ciona genomes and generate predictions about the number of monocistronic, nonoperon genes that likely participate in the birth-death process", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Operons are a conserved feature of nematode genomes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "The organization of genes into operons, clusters of genes that are co-transcribed to produce polycistronic pre-mRNAs, is a trait found in a wide range of eukaryotic groups, including multiple animal phyla", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 288, "text": "Operons are present in the class Chromadorea, one of the two main nematode classes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "endSection": "abstract" }, { "offsetInBeginSection": 1391, "offsetInEndSection": 1632, "text": " Our data suggest that operons and \"spliced leader\" (SL) trans-splicing predate the radiation of the nematode phylum, an inference which is supported by the phylogenetic profile of proteins known to be involved in nematode SL trans-splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24931407", "endSection": "abstract" }, { "offsetInBeginSection": 1681, "offsetInEndSection": 1795, "text": "Instead operons, polycistronic transcriptional units common in derived nematodes, seemingly adopted their function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18218978", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 754, "text": "To test this hypothesis, we analyzed the presence and absence of C. elegans operons in Caenorhabditis briggsae, Caenorhabditis remanei, and Caenorhabditis brenneri, using Pristionchus pacificus and Brugia malayi as outgroups, and identified numerous operon gains and losses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18218978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "In the nematode Caenorhabditis elegans, up to 15% of the genes are organized in operons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12949121", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 441, "text": "Here we address this issue by analysing transcription termination at the end of single protein expressing genes and genes located within operons in the nematode Caenorhabditis elegans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19740764", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1104, "text": "We find that birth-death models of operon evolution reasonably describe the relative abundance of operons of different sizes in the C. elegans and Ciona genomes and generate predictions about the number of monocistronic, nonoperon genes that likely participate in the birth-death process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1239, "text": "This theory, and applications to C. elegans and Ciona, motivates several new and testable hypotheses about eukaryote operon evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Genes in nematode and ascidian genomes frequently occur in operons--multiple genes sharing a common promoter to generate a polycistronic primary transcript--and such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 981, "text": "e operon structure in the eukaryote Caenorhabditis elegans genome is a valuable, though underserved, tool for identifying physically or functionally interacting proteins. Based on the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24429814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "The genome of the nematode Caenorhabditis elegans is unusual among eukaryotes, in that it contains operons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17174523", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 546, "text": "This is one of the largest operons identified thus far in the C. elegans genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17174523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "The frataxin-encoding operon of Caenorhabditis elegans shows complex structure and regulation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17174523", "endSection": "title" }, { "offsetInBeginSection": 394, "offsetInEndSection": 465, "text": "The C. elegans frataxin gene, frh-1, is encoded in the operon CEOP2232.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17174523", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 272, "text": "There are instances of operons found in C. elegans, Drosophila melanogaster and other eukaryotic species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23668349", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1197, "text": "Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 661, "text": "Although only 28 operons have been reported, the complete sequence of the C. elegans genome reveals numerous gene clusters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "endSection": "abstract" } ] }, { "body": "What has capmatinib received FDA approval for in 2020?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32557339" ], "ideal_answer": [ "In May 2020, oral capmatinib received its first global approval in the USA for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have a mutation that leads to MET exon 14 skipping, as detected by an FDA-approved test." ], "type": "summary", "id": "606b79da94d57fd87900006e", "snippets": [ { "offsetInBeginSection": 386, "offsetInEndSection": 644, "text": " In May 2020, oral capmatinib received its first global approval in the USA for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have a mutation that leads to MET exon 14 skipping, as detected by an FDA-approved test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32557339", "endSection": "abstract" } ] }, { "body": "Is SLIC-CAGE used for quantification of translation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "http://www.ncbi.nlm.nih.gov/pubmed/31305534" ], "ideal_answer": [ "No. Cap analysis of gene expression (CAGE) is a method used for single-nucleotide resolution detection of RNA polymerase II transcription start sites (TSSs). Accurate detection of TSSs enhances identification and discovery of core promoters. In addition, active enhancers can be detected through signatures of bidirectional transcription initiation. Described here is a protocol for performing super-low input carrier-CAGE (SLIC-CAGE). The SLIC adaptation of the CAGE protocol minimizes RNA losses by artificially increasing the RNA amount through use of an in vitro transcribed RNA carrier mix that is added to the sample of interest, thus enabling library preparation from nanogram-amounts of total RNA (i.e., thousands of cells).", "No, the super-low input carrier-CAGE (SLIC-Cage) is not used for quantification of translation." ], "exact_answer": "no", "type": "yesno", "id": "601ec5661cb411341a000063", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Transcription Start Site Mapping Using Super-low Input Carrier-CAGE.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31305534", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1241, "text": "Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5' ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of the rules of transcription initiation, led to discovery of new core promoter sequence features, and discovered transcription initiation at enhancers genome-wide. The biggest limitation of CAGE is that even the most recently improved version (nAnT-iCAGE) still requires large amounts of total cellular RNA (5 \u00b5g), preventing its application to scarce biological samples such as those from early embryonic development or rare cell types. Here, we present SLIC-CAGE, a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods, by generating a complex, high-quality library from mouse embryonic day 11.5 primordial germ cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404778", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1814, "text": "Cap analysis of gene expression (CAGE) is a method used for single-nucleotide resolution detection of RNA polymerase II transcription start sites (TSSs). Accurate detection of TSSs enhances identification and discovery of core promoters. In addition, active enhancers can be detected through signatures of bidirectional transcription initiation. Described here is a protocol for performing super-low input carrier-CAGE (SLIC-CAGE). This SLIC adaptation of the CAGE protocol minimizes RNA losses by artificially increasing the RNA amount through use of an in vitro transcribed RNA carrier mix that is added to the sample of interest, thus enabling library preparation from nanogram-amounts of total RNA (i.e., thousands of cells). The carrier mimics the expected DNA library fragment length distribution, thereby eliminating biases that could be caused by the abundance of a homogenous carrier. In the last stages of the protocol, the carrier is removed through degradation with homing endonucleases and the target library is amplified. The target sample library is protected from degradation, as the homing endonuclease recognition sites are long (between 18 and 27 bp), making the probability of their existence in the eukaryotic genomes very low. The end result is a DNA library ready for next-generation sequencing. All steps in the protocol, up to sequencing, can be completed within 6 days. The carrier preparation requires a full working day; however, it can be prepared in large quantities and kept frozen at -80 \u00b0C. Once sequenced, the reads can be processed to obtain genome-wide single-nucleotide resolution TSSs. TSSs can be used for core promoter or enhancer discovery, providing insight into gene regulation. Once aggregated to promoters, the data can also be used for 5'-centric expression profiling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31305534", "endSection": "abstract" } ] }, { "body": "Does hypofractionated radiotherapy offers any benefit for DIPG?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31785177", "http://www.ncbi.nlm.nih.gov/pubmed/21327862", "http://www.ncbi.nlm.nih.gov/pubmed/33080729", "http://www.ncbi.nlm.nih.gov/pubmed/31728883", "http://www.ncbi.nlm.nih.gov/pubmed/24560760" ], "ideal_answer": [ "No. Hypofractionated radiotherapy does not offers benefit when compared to conventional fractionated radiation therapy for DIPG." ], "exact_answer": "no", "type": "yesno", "id": "6025fa371cb411341a0000be", "snippets": [ { "offsetInBeginSection": 1399, "offsetInEndSection": 1631, "text": "CONCLUSION: Hypofractionated RT for children with newly diagnosed DIPG is well tolerated and feasible from the viewpoint of reducing a patient's burden of treatment. Re-irradiation at first progression is suggested to be beneficial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31785177", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 1070, "text": "Median OS and time to progression were similar between conventionally fractionated and hypofractionated RT groups.(9.7 [95% confidence interval(CI): 7.1-11.2] versus 11.0[95% CI: 5.2-13.6] months, P = 0.60; 4.2[95% CI: 1.8-8.3] versus 7.1 [95% CI:4.5-8.7] months, P = 0.38). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31785177", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1464, "text": "The median overall survival (OS) was 11\u00a0months (95% CI - 7.5 to 14.5\u00a0months) in the conventional arm and 12\u00a0months (95% CI - 10.5 to 13.5\u00a0months) in the experimental arm (p\u2009=\u20090.208). 28% (n\u2009=\u20095) patients in the experimental arm developed grade 3 or 4 hematological toxicity.CONCLUSION: The above study shows that hypofractionated radiotherapy with concurrent and adjuvant temozolomide does not improve OS and has higher hematological toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31728883", "endSection": "abstract" }, { "offsetInBeginSection": 1157, "offsetInEndSection": 1288, "text": "CONCLUSIONS: The results of this meta-analysis suggest that CFRT and HFRT provide similar survival outcomes for patients with DIPG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33080729", "endSection": "abstract" }, { "offsetInBeginSection": 1131, "offsetInEndSection": 1372, "text": "CONCLUSIONS: Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24560760", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1449, "text": "xternal radiotherapy with a radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen does not seem to change overall survival in this setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21327862", "endSection": "abstract" } ] }, { "body": "What is the function of the stard10 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23200860", "http://www.ncbi.nlm.nih.gov/pubmed/15976441", "http://www.ncbi.nlm.nih.gov/pubmed/15911624" ], "ideal_answer": [ "STARD10, a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) protein family, is highly expressed in the liver and has been shown to transfer phosphatidylcholine." ], "exact_answer": [ "STARD10 is a lipid transfer protein" ], "type": "factoid", "id": "608069984e6a4cf630000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "STARD10, a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) protein family, is highly expressed in the liver and has been shown to transfer phosphatidylcholine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23200860", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 327, "text": "StarD10 contains a steroidogenic acute regulatory protein (StAR/StarD1)-related lipid transfer (START) domain that is thought to mediate binding of lipids. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15911624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain is a protein module of approximately 210 residues that binds lipids, including sterols", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15976441", "endSection": "abstract" } ] }, { "body": "Is progeria caused by an autosomal recessive gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17664768", "http://www.ncbi.nlm.nih.gov/pubmed/28660486", "http://www.ncbi.nlm.nih.gov/pubmed/17028399", "http://www.ncbi.nlm.nih.gov/pubmed/22971867", "http://www.ncbi.nlm.nih.gov/pubmed/27617860", "http://www.ncbi.nlm.nih.gov/pubmed/29149836", "http://www.ncbi.nlm.nih.gov/pubmed/32360386", "http://www.ncbi.nlm.nih.gov/pubmed/21365542", "http://www.ncbi.nlm.nih.gov/pubmed/32596971", "http://www.ncbi.nlm.nih.gov/pubmed/3228132", "http://www.ncbi.nlm.nih.gov/pubmed/32528764", "http://www.ncbi.nlm.nih.gov/pubmed/17375009", "http://www.ncbi.nlm.nih.gov/pubmed/27931782", "http://www.ncbi.nlm.nih.gov/pubmed/19432833", "http://www.ncbi.nlm.nih.gov/pubmed/16598422", "http://www.ncbi.nlm.nih.gov/pubmed/16838330", "http://www.ncbi.nlm.nih.gov/pubmed/17219342", "http://www.ncbi.nlm.nih.gov/pubmed/19875478", "http://www.ncbi.nlm.nih.gov/pubmed/33087645" ], "ideal_answer": [ "Yes. Progeria is caused by an autosomal recessive gene.", "yes, progeria is caused by an autosomal recessive gene." ], "exact_answer": "yes", "type": "yesno", "id": "601d72e61cb411341a000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is an autosomal-dominant genetic disease that leads to accelerated aging and often premature death caused by cardiovascular complications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32596971", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Hutchinson-Gilford progeria syndrome is an autosomal dominant, rare, fatal pediatric segmental premature aging disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32360386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Progeria is sporadic, very rare, autosomal dominant, deadly childhood disorder. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28660486", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27931782", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 316, "text": "Among them, the most studied is Werner's syndrome, \"adult progeria\", caused by a recessive autosomal mutation with a frequency of 1 in 10 million, which affects a helicase involved in DNA repair.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29149836", "endSection": "abstract" }, { "offsetInBeginSection": 1829, "offsetInEndSection": 1915, "text": "Pattern of inheritance of non-classical progeria is most probably autosomal recessive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16838330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "INTRODUCTION: Werner Syndrome, or adult progeria, is a rare autosomal recessive disorder caused by a mutation in the Werner Syndrome Gene belonging to the family of RecQ helicase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16598422", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 921, "text": "SION: Werner's syndrome is a rare form of progeria with an autosomal recessive mode of inheritance mimicking the symptoms of accelerated aging. The r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17219342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Werner's Syndrome (WS) or adult-onset progeria is an autosomal recessive disorder of accelerated aging caused by mutations of the DNA RecQ helicase/exonuclease (WRN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21365542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Homozygous LMNA mutation R527C in atypical Hutchinson-Gilford progeria syndrome: evidence for autosomal recessive inheritance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19432833", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Progeria (Hutchison-Gilford syndrome) in siblings: in an autosomal recessive pattern of inheritance.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664768", "endSection": "title" }, { "offsetInBeginSection": 276, "offsetInEndSection": 379, "text": "The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Patie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27931782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "CONTEXT: Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia are well-recognized allelic autosomal dominant and recessive progeroid disorders, respectively, due to mutations in lamin A/C (LMNA) gen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19875478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Werner's syndrome (adult onset progeria) is a rare form of autosomal recessive genodermatosis associated in almost 80% of cases with mutation of the WRN gene. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17375009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner sy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33087645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Werner's syndrome (WS) or progeria adultorum is a heritable autosomal recessive disease in which the aging process is accelerated, just after puberty. It is", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32528764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617860", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1201, "text": "Furthermore, administration of JH4 to LmnaG609G/G609G-mutant mice, which phenocopy human HGPS, resulted in a marked improvement of several progeria phenotypes and an extended lifespan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Interruption of progerin-lamin A/C binding ameliorates Hutchinson-Gilford progeria syndrome phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27617860", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Progeria is an autosomal dominant, premature aging syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17664768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "INTRODUCTION: Werner Syndrome, or adult progeria, is a rare autosomal recessive disorder caused by a mutation in the Werner Syndrome Gene belonging to the family of RecQ helicase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16598422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Evidence for autosomal recessive inheritance of progeria (Hutchinson Gilford).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3228132", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "INTRODUCTION: Werner Syndrome, or adult progeria, is a rare autosomal recessive disorder caused by a mutation in the Werner Syndrome Gene belonging to the family of ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16598422", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Hutchinson-Gilford progeria causing premature aging of children is a genetic disease and according to most authors has an autosomal dominant inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17028399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Werner's syndrome (WS) or progeria adultorum is a heritable autosomal recessive disease in which the aging process is accelerated, just after puberty.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32528764", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33087645", "endSection": "abstract" } ] }, { "body": "What is the target of adalimumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16164218", "http://www.ncbi.nlm.nih.gov/pubmed/18680684", "http://www.ncbi.nlm.nih.gov/pubmed/30701218", "http://www.ncbi.nlm.nih.gov/pubmed/25381481", "http://www.ncbi.nlm.nih.gov/pubmed/19707417", "http://www.ncbi.nlm.nih.gov/pubmed/29752913", "http://www.ncbi.nlm.nih.gov/pubmed/23928807", "http://www.ncbi.nlm.nih.gov/pubmed/24774505", "http://www.ncbi.nlm.nih.gov/pubmed/29171393", "http://www.ncbi.nlm.nih.gov/pubmed/21744772", "http://www.ncbi.nlm.nih.gov/pubmed/24069534", "http://www.ncbi.nlm.nih.gov/pubmed/15379777", "http://www.ncbi.nlm.nih.gov/pubmed/16255652", "http://www.ncbi.nlm.nih.gov/pubmed/22540283", "http://www.ncbi.nlm.nih.gov/pubmed/19128982", "http://www.ncbi.nlm.nih.gov/pubmed/28516879" ], "ideal_answer": [ "adalimumab is an anti-tumour necrosis factor (tf)-\u03b1 antibody.", "Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor-alpha, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy. Targeted drugs against key pathogenetic molecules such as TNF-alpha have significantly improved outcomes in rheumatoid arthritis (RA). They are widely used in clinical practice and drug registries give us information to support their use.", "Adalimumab is a fully human anti-TNF-alpha IgG1-\u03ba monoclonal antibody.", "Adalimumab is a fully human monoclonal antibody against TNF-alpha.", "The objective of this study was to assess the relative importance of local versus systemic interactions between adalimumab and tumour necrosis factor (TNF)-\u03b1 in rheumatoid arthritis (RA), identify localization of the site of adalimumab action and assess the efficacy of local (intra-articular) versus systemic adalimumab administration for treatment of RA", "Adalimumab is a monoclonal antibody that targets TNF-alpha, a central cytokine in the immune response in psoriasis that has been linked to autoimmune disease.", "Adalimumab is a fully human anti-TNF-alpha monoclonal antibody.", "Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor-alpha, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy.", "Adalimumab is a human anti-TNF\u03b1 monoclonal antibody that has been reported to demonstrate clinical efficacy and safety, resulting in reversal of epidermal hyperplasia and cutaneous inflammation. The major pathway of TNF\u03b1 elimination from the synovial fluid (\u223c77% for subcutaneous administration, and \u223c72% for intravenous and intra-articular administration of adgalimumab 40 mg) is interaction with adalumumab, which reaches the joints following local or systemic administration." ], "exact_answer": [ "TNF", "TNF\u03b1", "Tumor Necrosis Factor alpha" ], "type": "factoid", "id": "5fe31305a43ad3127800003b", "snippets": [ { "offsetInBeginSection": 532, "offsetInEndSection": 887, "text": "The objective of this study was to assess the relative importance of local versus systemic interactions between adalimumab and tumour necrosis factor (TNF)-\u03b1 in rheumatoid arthritis (RA), identify localization of the site of adalimumab action and assess the efficacy of local (intra-articular) versus systemic adalimumab administration for treatment of RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540283", "endSection": "abstract" }, { "offsetInBeginSection": 2527, "offsetInEndSection": 2927, "text": "The kinetics of adalimumab permeation to the synovial fluid (0.00422 L/h clearance of permeation) versus the rate of TNF\u03b1 turnover in the affected joints (1.84 pmol/h synthesis rate and 0.877 h(-1) degradation rate constant) are apparently the major parameters that determine the time course of TNF\u03b1 concentrations in the synovial fluid and the TNF\u03b1-neutralizing effects of adalimumab in RA patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540283", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 412, "text": "Adalimumab is the first fully human monoclonal antibody directed against TNF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24774505", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 382, "text": "Adalimumab (ADA) is able to induce a comprehensive disease control in RA by achieving clinical, functional and radiographic control", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516879", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 249, "text": "Targeted drugs against key pathogenetic molecules such as TNF-alpha have significantly improved outcomes in rheumatoid arthritis (RA). They are widely used in clinical practice and drug registries give us information to support their use", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28516879", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 463, "text": "Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor-alpha, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15379777", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 420, "text": "Adalimumab is a human anti-TNF\u03b1 monoclonal antibody that has been reported to demonstrate clinical efficacy and safety, resulting in reversal of epidermal hyperplasia and cutaneous inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171393", "endSection": "abstract" }, { "offsetInBeginSection": 2236, "offsetInEndSection": 2518, "text": "major pathway of TNF\u03b1 elimination from the synovial fluid (\u223c77% for subcutaneous administration, and \u223c72% for intravenous and intra-articular administration of adalimumab 40 mg) is interaction with adalimumab, which reaches the joints following local or systemic administration.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540283", "endSection": "abstract" }, { "offsetInBeginSection": 1502, "offsetInEndSection": 1608, "text": "eability of TNF\u03b1, which is excessively secreted in the joints, is even higher than that of adalimumab. As ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22540283", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 411, "text": "Adalimumab is the first fully human monoclonal antibody directed against TNF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24774505", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 629, "text": "Most currently available molecules target TNF-alfa with different strategies (i.e., etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol), IL-6 (tocilizumab), CTLA-4 (abatacept), and B cells (rituximab, belimumab) as they are key mediators in the cascade of inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25381481", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 555, "text": "ces in knowledge of the pathogenesis of psoriasis have enabled the development of new drugs that target cytokines (e.g., etanercept, adalimumab, and infliximab, which target TNF \u03b1 , and ustekinumab, which targets the p40 subunit of IL23 and IL12). These drugs ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24069534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "There are currently two Food and Drug Administration-approved classes of biologic agents that target tumor necrosis factor-alpha (TNF-alpha): anti-TNF monoclonal antibodies (mAbs) (adalimumab and infliximab), and soluble TNF receptors (etanercept). This st", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19128982", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 565, "text": "meric anti-TNFalpha monoclonal antibody, infliximab, full human anti-TNFalpha monoclonal antibody, adalimumab, and TNF receptor II (p75) -IgGFc fusion protein, etanercept, are widely used in the inflammatory disorders including RA. This review arti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16164218", "endSection": "abstract" }, { "offsetInBeginSection": 347, "offsetInEndSection": 651, "text": "urrently available molecules target TNF-alfa with different strategies (i.e., etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol), IL-6 (tocilizumab), CTLA-4 (abatacept), and B cells (rituximab, belimumab) as they are key mediators in the cascade of inflammation. Further, small molecu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25381481", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 638, "text": "clonal antibodies against VEGF and TNF-alpha such as bevacizumab, ranibizumab, infliximab and adalimumab have been used to control neovascularization and inflammation in eye with significant positive results whereas others have been used to target CD20, CD52, CD11a, and IL-2. The growin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21744772", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 740, "text": "eview focuses on five biologics which target either T-cells (alefacept) or TNF-alpha (etanercept, adalimumab and infliximab) or interleukin IL-12/IL-23 (ustekinumab)--their efficacy, safety, patient monitoring and recommended dosage. The purpose of", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928807", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 477, "text": "Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) alpha approved for moderate-to-severe plaque-type psoriasis and psoriatic arthritis (PsA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707417", "endSection": "abstract" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1006, "text": "In clinical practice patients who have not responded to one TNF antagonist may respond to another TNF antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19707417", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 527, "text": "The ADAbs can diminish the therapeutic effects of adalimumab by neutralizing the TNF\u03b1 binding site or increasing its clearance from circulation.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29752913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Adalimumab is a fully human monoclonal antibody targeted toward tumor necrosis factor alpha (TNF-alpha).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18680684", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 238, "text": "Adalimumab (Humira, Abbott Laboratories) is the first fully human, recombinant IgG1 monoclonal antibody that specifically targets human TNF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16255652", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 380, "text": "Adalimumab blocks the interaction of TNF with the p55 and p75 cell surface TNF receptors, thereby neutralising the activity of this cytokine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16255652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Adalimumab is a human monoclonal antibody which targets tumor necrosis factor (TNF)-alpha.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30701218", "endSection": "abstract" } ] }, { "body": "Which gene is implicated in the metabolism of codeine, and its polymorphisms in the mother can pose a risk to breastfeeding children?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28696420" ], "ideal_answer": [ "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine." ], "exact_answer": [ "CYP2D6" ], "type": "factoid", "id": "606ae4fd94d57fd879000056", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28696420", "endSection": "abstract" } ] }, { "body": "Describe the role of epidermal CYLD inactivation in sebaceous and basaloid skin tumors", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27478875" ], "ideal_answer": [ "Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors. Epidermal cyld inactivation also inhibits the growth of epidermal cell lines, leading to development of skin tumors in the early phase of the disease.", "Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors. The deubiquitinase-encoding gene Cyld displays a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDm-syndrome).", "Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors.", "The deubiquitinase-encoding CYLDM gene is a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDM-Syndrome). It's a dominant gene in the basaloid and sebaceous regions of the epidermis, which is the outermost layer of the skin. When it's mutated, it can lead to a variety of skin tumors.", "The deubiquitinase-encoding gene Cyld displays a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDm-syndrome). Despite recent advances, little is understood about the molecular mechanisms responsible for this painful and difficult-to-treat skin disease. Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors." ], "type": "summary", "id": "6026b0e01cb411341a0000ca", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27478875", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1451, "text": "The deubiquitinase-encoding gene Cyld displays a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDm-syndrome). Despite recent advances, little is understood about the molecular mechanisms responsible for this painful and difficult-to-treat skin disease. Here, we generated a conditional mouse model with epidermis-targeted expression of a catalytically deficient CYLDm through K14-Cre-mediated deletion of exon 9 (hereafter refer to CyldE\u03949/\u03949 ). CyldE\u03949/\u03949 mice were born alive but developed hair and sebaceous gland abnormalities and dental defects at 100% and 60% penetrance, respectively. Upon topical challenge with DMBA/TPA, these animals primarily developed sebaceous and basaloid tumors resembling human CYLDm-syndrome as opposed to papilloma, which is most commonly induced in WT mice by this treatment. Molecular analysis revealed that TRAF6-K63-Ubiquitination (K63-Ub), c-Myc-K63-Ub, and phospho-c-Myc (S62) were markedly elevated in CyldE\u03949/\u03949 skin. Topical treatment with a pharmacological c-Myc inhibitor induced sebaceous and basal cell apoptosis in CyldE\u03949/\u03949 skin. Consistently, c-Myc activation was readily detected in human cylindroma and sebaceous adenoma. Taken together, our findings demonstrate that CyldE\u03949/\u03949 mice represent a disease-relevant animal model and identify TRAF6 and c-Myc as potential therapeutic targets for CYLDm-syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27478875", "endSection": "abstract" } ] }, { "body": "Describe the mechanism of action of Lisocabtagene maraleucel.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31899702", "http://www.ncbi.nlm.nih.gov/pubmed/32611216", "http://www.ncbi.nlm.nih.gov/pubmed/32670869", "http://www.ncbi.nlm.nih.gov/pubmed/32888407", "http://www.ncbi.nlm.nih.gov/pubmed/31677848", "http://www.ncbi.nlm.nih.gov/pubmed/31099671", "http://www.ncbi.nlm.nih.gov/pubmed/31648957", "http://www.ncbi.nlm.nih.gov/pubmed/32740094" ], "ideal_answer": [ "Lisocabtagene maraleucel is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product." ], "type": "summary", "id": "602745c51cb411341a0000de", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Antitumor Potency of an Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, Lisocabtagene Maraleucel in Combination With Ibrutinib or Acalabrutinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31899702", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 507, "text": "Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for patients with CD19 B-cell malignancies. Combination strategies that improve CAR T-cell potency, limit tumor environment-mediated immune dysfunction, and directly reduce tumor burden may increase the potential for durable clinical benefit of CAR T-cell therapy. Lisocabtagene maraleucel (liso-cel) is a product therapy candidate being tested in patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31899702", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 451, "text": "Two second-generation anti-CD19 CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for use in patients, and the approval of a third product, lisocabtagene maraleucel, is expected in 2020.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32670869", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 268, "text": "Currently, three CAR T-cell products are approved or soon to be approved: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32611216", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 870, "text": "Since the first report of CD19-directed CAR-T-cell therapy in 2010, three constructs have been tested in large phase I/II trials and resulted in 30-40% durable responses. This has led to Food and Drug Administration and European Medicines Agency approval for axicabtagene ciloleucel and tisagenlecleucel and filing of the biologics license application for lisocabtagene maraleucel. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32740094", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888407", "endSection": "abstract" }, { "offsetInBeginSection": 1401, "offsetInEndSection": 1750, "text": "Here we provide a thorough review on the use of the anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma or with chronic lymphocytic leukemia, and present novel CAR T cell-based approaches currently under investigation in these disease settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32670869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888407", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 597, "text": "hree anti-CD19 CAR T-cells are currently Food and Drug Administration and European Medicines Agency approved or in advanced-stage development: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31677848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888407", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 626, "text": "A third anti CD19 CAR-T cell, lisocabtagene ciloleucel is currently being evaluated in large clinical trials and may also be United States Food and Drug Administration-approved soon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31648957", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 821, "text": "Three anti-CD19 CAR T cells for aggressive B-cell lymphoma (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene ciloleucel) are either U.S. Food and Drug Administration approved or in late-stage development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31099671", "endSection": "abstract" } ] }, { "body": "What is the cause of the Kleefstra syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32531423", "http://www.ncbi.nlm.nih.gov/pubmed/32975655", "http://www.ncbi.nlm.nih.gov/pubmed/30585561", "http://www.ncbi.nlm.nih.gov/pubmed/31750954", "http://www.ncbi.nlm.nih.gov/pubmed/32539280" ], "ideal_answer": [ "Mutations in the Euchromatic Histone Methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a rare form of intellectual disability (ID) with strong autistic traits and sensory processing deficits." ], "exact_answer": [ "Mutations in the Euchromatic Histone Methyltransferase 1 (EHMT1)" ], "type": "factoid", "id": "60805e204e6a4cf630000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Kleefstra syndrome is a rare neurogenetic disorder caused by a subtelomeric 9q34.3 deletion or by an intragenic mutation of the euchromatin histone methyl transferase 1 gene (EHMT1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31750954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Kleefstra syndrome is a disorder caused by a mutation in the EHMT1 gene characterized in humans by general developmental delay, mild to severe intellectual disability and autism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32531423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Kleefstra syndrome (KS) is an autosomal dominant disorder caused by a chromosomal deletion at 9q34.3 resulting in pathogenic variants of the gene that codes for the enzyme, euchromatin histone methyltransferase 1 (EHMT1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32539280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Mutations in the Euchromatic Histone Methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a rare form of intellectual disability (ID) with strong autistic traits and sensory processing deficits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32975655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Kleefstra syndrome (chromosome 9q34.3 deletion) is a rare genetic disorder with less than 110 patients reported till date. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30585561", "endSection": "abstract" } ] }, { "body": "Is acupotomy used to treat muscle stiffness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29620626", "http://www.ncbi.nlm.nih.gov/pubmed/33178308", "http://www.ncbi.nlm.nih.gov/pubmed/31852126", "http://www.ncbi.nlm.nih.gov/pubmed/33014527", "http://www.ncbi.nlm.nih.gov/pubmed/32190087", "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "http://www.ncbi.nlm.nih.gov/pubmed/33010179", "http://www.ncbi.nlm.nih.gov/pubmed/30681588", "http://www.ncbi.nlm.nih.gov/pubmed/31399459", "http://www.ncbi.nlm.nih.gov/pubmed/32506848", "http://www.ncbi.nlm.nih.gov/pubmed/31383431", "http://www.ncbi.nlm.nih.gov/pubmed/32280270", "http://www.ncbi.nlm.nih.gov/pubmed/29890806", "http://www.ncbi.nlm.nih.gov/pubmed/31277532", "http://www.ncbi.nlm.nih.gov/pubmed/26345906" ], "ideal_answer": [ "Yes. Acupotomy has been widely used to treat nerve entrapment syndrome. URL_0", "Acupotomy has been used to treat frozen shoulder, cervical spondylosis, third lumbar vertebrae transverse process syndrome, trigger finger, knee osteoarthritis, and lumbar spinal stenosis." ], "exact_answer": "no", "type": "yesno", "id": "601d73c71cb411341a00003e", "snippets": [ { "offsetInBeginSection": 572, "offsetInEndSection": 925, "text": "All the included studies reviewed musculoskeletal disorders and reported a significantly higher total effective and cure rates in the acupotomy group for frozen shoulder, cervical spondylosis, third lumbar vertebrae transverse process syndrome, trigger finger, knee osteoarthritis, and lumbar spinal stenosis, compared to the other active control groups", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383431", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1121, "text": "Acupotomy showed promising results for some musculoskeletal disorders; however, additional high-quality evidence is required to make clinical recommendations regarding this procedure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383431", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 77, "text": "Acupotomy has been widely used to treat nerve entrapment syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31852126", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 105, "text": "To evaluate the clinical efficacy and safety of acupotomy in treatment of knee osteoarthritis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32506848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Effect and safety of acupotomy in treatment of knee osteoarthritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32506848", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Acupotomy Therapy for Knee Osteoarthritis Pain: Systematic Review and Meta-Analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33178308", "endSection": "title" }, { "offsetInBeginSection": 156, "offsetInEndSection": 286, "text": "We included only randomized controlled trials (RCTs) that used acupotomy therapy as the major intervention in adults with knee OA,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33178308", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 209, "text": "Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a conservative treatment method for lumbar disc herniation (LDH)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280270", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1007, "text": "LTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 197, "text": "Acupotomy has been widely used to treat KOA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 337, "text": "Acupotomy, a biomechanical therapy guided by traditional Chinese medicine theory, alleviates cartilage degradation and is widely used in the clinic to treat KOA by correcting abnormal mechanics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33014527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "BACKGROUND: Acupotomy has been widely used to treat nerve entrapment syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31852126", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 266, "text": "Acupotomy has been widely used to treat calcaneodynia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29620626", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 461, "text": "The aim of this study is to evaluate the efficacy and safety of the acupotomy treatment in patients with calcaneodynia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29620626", "endSection": "abstract" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1682, "text": "otomy combined with rehabilitation was associated with significantly higher TER (RR 1.24, 95% CI 1.01-1.52, I\u200a=\u200a77%) and gross motor function measure score (MD 12.62, 95% CI 11.75-13.49, I\u200a=\u200a54%), and significantly lower muscle tone of gastrocnemius measured by the Ashworth scale or the modified Ashworth scale (MD -0.97, 95% CI -1.07 to -0.88, I\u200a=\u200a0%) compared with rehabilitation alone. No ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30681588", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 269, "text": "Both acupotomy and acupuncture have been widely used clinically to treat CSR in China with satisfied efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31399459", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 392, "text": "GN AND METHODS: Total 75 patients were participated in acupotomy therapy and ultrasonic drug penetration to treat joint osteoarthritis. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33010179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Acupotomy Alleviates Energy Crisis at Rat Myofascial Trigger Points", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32190087", "endSection": "title" }, { "offsetInBeginSection": 567, "offsetInEndSection": 736, "text": "its in the acupotomy and EA groups underwent bilateral acupotomylysis intervention; those in the acupotomy-EA group underwent acupotomylysis and EA interventions. On the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26345906", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1006, "text": "LTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events.CON", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Acupotomy for knee osteoarthritis: A systematic review protocol.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "title" }, { "offsetInBeginSection": 272, "offsetInEndSection": 385, "text": " The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1141, "text": "SION: The systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients.PROSP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 795, "offsetInEndSection": 1006, "text": "e systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events.CON", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 387, "text": "The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1140, "text": " systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients.PROS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574849", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 159, "text": "To observe the clinical efficacy of minimally invasive acupotomy-injection technique with targeted three-point in the treatment of frozen shoulder.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31277532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "[Percutaneous dynamic release in stress position by acupotomy in treating severe scapulohumeral periarthritis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29890806", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 141, "text": "To investigate the clinical efficacy of acupotomy stress position percutaneous dynamic release for severe shoulder periarthritis.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29890806", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 303, "text": "l sequelae. Acupotomy, a modernized acupuncture form combining the effects of microsurgery and conventional acupuncture, may show specific benefits in the treatment of CP, especially with respect to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30681588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Background: Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a conservative treatment method for lumbar disc herni", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32280270", "endSection": "abstract" }, { "offsetInBeginSection": 516, "offsetInEndSection": 1053, "text": "he methodological quality was medium-to-high in AMSTAR. All the included studies reviewed musculoskeletal disorders and reported a significantly higher total effective and cure rates in the acupotomy group for frozen shoulder, cervical spondylosis, third lumbar vertebrae transverse process syndrome, trigger finger, knee osteoarthritis, and lumbar spinal stenosis, compared to the other active control groups.CONCLUSION: Acupotomy showed promising results for some musculoskeletal disorders; however, additional high-quality evidence is", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31383431", "endSection": "abstract" } ] }, { "body": "Which is the role of mediator in genome organization?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24998386", "http://www.ncbi.nlm.nih.gov/pubmed/27773677", "http://www.ncbi.nlm.nih.gov/pubmed/29157917", "http://www.ncbi.nlm.nih.gov/pubmed/29209056", "http://www.ncbi.nlm.nih.gov/pubmed/31211995", "http://www.ncbi.nlm.nih.gov/pubmed/31209209", "http://www.ncbi.nlm.nih.gov/pubmed/26240385", "http://www.ncbi.nlm.nih.gov/pubmed/24824069", "http://www.ncbi.nlm.nih.gov/pubmed/27742736", "http://www.ncbi.nlm.nih.gov/pubmed/28575439", "http://www.ncbi.nlm.nih.gov/pubmed/33176147" ], "ideal_answer": [ "Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly.", "Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4. Together with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement.", "mediator binds to boundaries of chromosomal interaction domains and to proteins involved in dna looping, rna metabolism, chromatin remodeling, and actin assembly.. mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to rna polymerase ii in eukaryotes.", "Mediator plays a significant role in higher-order genome organization. Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4" ], "type": "summary", "id": "5fdb40eba43ad31278000014", "snippets": [ { "offsetInBeginSection": 1160, "offsetInEndSection": 1230, "text": "Mediator plays a significant role in higher-order genome organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28575439", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1139, "text": "Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28575439", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 539, "text": "Together with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27742736", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 676, "text": "By defining the organizational hierarchy of the genome, determining changes in chromatin organization associated with changes in cell identity, and describing chromatin organization within the context of linear genomic features (such as chromatin modifications and transcription factor binding) and architectural proteins (including Cohesin, CTCF, and Mediator), a new paradigm in genome biology was established wherein genomes are organized around gene regulatory factors that govern cell identity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28575439", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to RNA polymerase II in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28575439", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 675, "text": "By defining the organizational hierarchy of the genome, determining changes in chromatin organization associated with changes in cell identity, and describing chromatin organization within the context of linear genomic features (such as chromatin modifications and transcription factor binding) and architectural proteins (including Cohesin, CTCF, and Mediator), a new paradigm in genome biology was established wherein genomes are organized around gene regulatory factors that govern cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24998386", "endSection": "abstract" }, { "offsetInBeginSection": 1141, "offsetInEndSection": 1230, "text": "This suggests that Mediator plays a significant role in higher-order genome organization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28575439", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 549, "text": "er with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement. Although ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27742736", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Loss of nuclear pore complex (NPC) proteins, transcription factors (TFs), histone modification enzymes, Mediator, and factors involved in mRNA export disrupts the physical interaction of chromosomal sites with NPCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31211995", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 380, "text": "Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157917", "endSection": "abstract" }, { "offsetInBeginSection": 1211, "offsetInEndSection": 1376, "text": "This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26240385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26240385", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 588, "text": "In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26240385", "endSection": "abstract" }, { "offsetInBeginSection": 965, "offsetInEndSection": 1117, "text": "Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31209209", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 668, "text": "These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24824069", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1210, "text": "We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26240385", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1046, "text": "Collectively, our data suggest that the essential function of Mediator is mediated by Head and Middle at core promoters, while Tail and CKM play regulatory roles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27773677", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27773677", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 589, "text": "Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "The Mediator complex regulates transcription by connecting enhancers to promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31209209", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 790, "text": "Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29157917", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 674, "text": "The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29209056", "endSection": "abstract" }, { "offsetInBeginSection": 1040, "offsetInEndSection": 1248, "text": "Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29209056", "endSection": "abstract" } ] }, { "body": "Which two antibodies directed towards the CGRP ligand, were approved by the FDA in September 2018.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30550780" ], "ideal_answer": [ "Two antibodies, fremanezumab and galcanezumab, directed towards the CGRP ligand, were approved by the FDA in September 2018." ], "exact_answer": [ [ "Fremanezumab" ], [ "Galcanezumab" ] ], "type": "list", "id": "6028fc001cb411341a000102", "snippets": [ { "offsetInBeginSection": 323, "offsetInEndSection": 448, "text": "Two antibodies, fremanezumab and galcanezumab, directed towards the CGRP ligand, were approved by the FDA in September 2018. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550780", "endSection": "abstract" } ] }, { "body": "Describe LowMACA", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26860319" ], "ideal_answer": [ "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver mutations through the identification of their mutational hotspots. Low MACA is an R package available at http://www.bioconductor.org/packages/release/bioc/html/LowMCCC.html.", "LowMACA is a software for the identification of gain-of-function mutations in putative oncogenic families, increasing the amount of information on functional domains and their possible role in cancer. In this context LowMACA emphasizes the role of genes mutated at low frequency otherwise undetectable by classical single gene analysis.", "LowMACA is a computational tool for the analysis and visualization of somatic mutation data in cancer.", "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a software for the identification of gain-of-function mutations in putative oncogenic families, increasing the amount of information on functional domains and their possible role in cancer. In this context LowMACA emphasizes the role of genes mutated at low frequency otherwise undetectable by classical single gene analysis. LowMACA is an R package available at http://www.bioconductor.org/packages/release/bioc/html/LowMACA.html. It is also available as a GUI standalone downloadable at: https://cgsb.genomics.iit.it/wiki/projects/LowMACA.", "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver mutations through the identification of their mutational hotspots.", "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is exploiting protein family analysis for the identification of rare driver mutations in cancer.", "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver genes through the identification of their mutational hotspots. It is an R package available at http://www.bioconductor.org/packages/release/bioc/html/ lowMACA.html.", "LowMACA is designed to visualize and statistically assess potential driver genes through the identification of their mutational hotspots.", "LowMACA is a software that combines the mutations of various proteins sharing the same domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments." ], "type": "summary", "id": "6032536a1cb411341a00013b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "LowMACA: exploiting protein family analysis for the identification of rare driver mutations in cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26860319", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 792, "text": "The increasing availability of resequencing data has led to a better understanding of the most important genes in cancer development. Nevertheless, the mutational landscape of many tumor types is heterogeneous and encompasses a long tail of potential driver genes that are systematically excluded by currently available methods due to the low frequency of their mutations. We developed LowMACA (Low frequency Mutations Analysis via Consensus Alignment), a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver genes through the identification of their mutational hotspots.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26860319", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1802, "text": "LowMACA is a software for the identification of gain-of-function mutations in putative oncogenic families, increasing the amount of information on functional domains and their possible role in cancer. In this context LowMACA emphasizes the role of genes mutated at low frequency otherwise undetectable by classical single gene analysis. LowMACA is an R package available at http://www.bioconductor.org/packages/release/bioc/html/LowMACA.html. It is also available as a GUI standalone downloadable at: https://cgsb.genomics.iit.it/wiki/projects/LowMACA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26860319", "endSection": "abstract" } ] }, { "body": "Is ofatumumab effective for multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33092190", "http://www.ncbi.nlm.nih.gov/pubmed/33107072", "http://www.ncbi.nlm.nih.gov/pubmed/30985372", "http://www.ncbi.nlm.nih.gov/pubmed/30604390", "http://www.ncbi.nlm.nih.gov/pubmed/29695594", "http://www.ncbi.nlm.nih.gov/pubmed/30539801", "http://www.ncbi.nlm.nih.gov/pubmed/33090003", "http://www.ncbi.nlm.nih.gov/pubmed/30632834", "http://www.ncbi.nlm.nih.gov/pubmed/24453078", "http://www.ncbi.nlm.nih.gov/pubmed/32757523" ], "ideal_answer": [ "Ofatumumab, a fully human anti-CD20 monoclonal antibody, is effective for relapsing forms of multiple sclerosis." ], "exact_answer": "yes", "type": "yesno", "id": "60234bd51cb411341a000093", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33092190", "endSection": "title" }, { "offsetInBeginSection": 1204, "offsetInEndSection": 1367, "text": "Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33092190", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 591, "text": "Conclusion: Ofatumumab offers beneficial outcomes for RMS\u00a0by reducing relapse and disability progression risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33090003", "endSection": "abstract" }, { "offsetInBeginSection": 659, "offsetInEndSection": 837, "text": "Currently, new therapies are emerging that promise more convenience and an improved safety profile (ofatumumab) or remyelinating potential with clinical improvement (opicinumab).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30604390", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 812, "text": "The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30539801", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 435, "text": "AREAS COVERED: In this manuscript, we review mechanisms of action, efficacy, safety, and tolerance of anti-CD20 therapies for MS, including rituximab, ocrelizumab, and ofatumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30632834", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 791, "text": "Another CD20 directed mAb, ofatumumab, is in phase 3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30985372", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 591, "text": "Ofatumumab offers beneficial outcomes for RMS\u00a0by reducing relapse and disability progression risk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33090003", "endSection": "abstract" }, { "offsetInBeginSection": 1296, "offsetInEndSection": 1493, "text": "CONCLUSION: Imaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses \u226530 mg/12 wk), with a safety profile consistent with existing ofatumumab data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29695594", "endSection": "abstract" }, { "offsetInBeginSection": 2318, "offsetInEndSection": 2453, "text": "CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32757523", "endSection": "abstract" } ] }, { "body": "List proteins that promotes calcification.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31852220", "http://www.ncbi.nlm.nih.gov/pubmed/30847765", "http://www.ncbi.nlm.nih.gov/pubmed/31768941" ], "ideal_answer": [ "tissue nonspecific alkaline phosphatase (TNAP)\nmatrix Gla protein (MGP)\nfibroblast growth factor-23 (FGF-23)\nmatrix metalloproteinases" ], "exact_answer": [ [ "tissue nonspecific alkaline phosphatase", "TNAP" ], [ "matrix Gla protein", "MGP" ], [ "fibroblast growth factor-23", "FGF-23" ], [ "matrix metalloproteinases" ] ], "type": "list", "id": "6082e2254e6a4cf63000000d", "snippets": [ { "offsetInBeginSection": 469, "offsetInEndSection": 625, "text": "several promoters and inhibitors of calcification (matrix Gla protein (MGP), fibroblast growth factor-23 (FGF-23), matrix metalloproteinases (MMP-2 and -9),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30847765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Primary familial brain calcification (PFBC), widely known as Fahr's disease, is a rare disorder caused by pathogenic variants in SLC20A2, PDGFB, PDGFRB, XPR1, or MYORG genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31768941", "endSection": "abstract" }, { "offsetInBeginSection": 890, "offsetInEndSection": 971, "text": " calcification-promoting TNAP (tissue nonspecific alkaline phosphatase) activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31852220", "endSection": "abstract" } ] }, { "body": "Please list 3 small molecule CGRP-Receptor antagonists for migraine", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32799325", "http://www.ncbi.nlm.nih.gov/pubmed/32020557", "http://www.ncbi.nlm.nih.gov/pubmed/19939188", "http://www.ncbi.nlm.nih.gov/pubmed/31932515", "http://www.ncbi.nlm.nih.gov/pubmed/30725283", "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "http://www.ncbi.nlm.nih.gov/pubmed/31096904", "http://www.ncbi.nlm.nih.gov/pubmed/32173558", "http://www.ncbi.nlm.nih.gov/pubmed/31020659", "http://www.ncbi.nlm.nih.gov/pubmed/32058712" ], "ideal_answer": [ "Rimegepant and ubrogepant have been developed for acute migraine treatment, while atogepant is studied for migraine prophylaxis." ], "exact_answer": [ [ "ubrogepant" ], [ "rimegepant" ], [ "atogepant" ] ], "type": "list", "id": "601f1bbd1cb411341a000074", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Ubrogepant (Ubrelvy\u2122) is an orally administered, small molecule, highly-selective, calcitonin gene-related peptide (CGRP) antagonist that was developed by Allergan under license to Merck & Co. as an acute treatment for migraine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32020557", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 524, "text": " This article summarizes the milestones in the development of ubrogepant leading to its first global approval for the acute treatment of migraine (\u00b1\u2009aura) in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32020557", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 382, "text": " a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody, can be used concomitantly to treat refractory migraine.METHODS: Case reports are presented of 2 patients participating in a long-term safety study of rimegepant 75 mg oral tablets for acute treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31932515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "The pivotal role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology was identified over 30 years ago, but the successful clinical development of targeted therapies has only recently been realized. This Perspective traces the decades long evolution of medicinal chemistry required to advance small molecule CGRP receptor antagonists, also called gepants, including the current clinical agents rimegepant, vazegepant, ubrogepant, and atogepant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32058712", "endSection": "abstract" }, { "offsetInBeginSection": 1167, "offsetInEndSection": 1305, "text": "Currently, rimegepant and ubrogepant have been developed for acute migraine treatment, while atogepant is studied for migraine prophylaxis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32173558", "endSection": "abstract" }, { "offsetInBeginSection": 1047, "offsetInEndSection": 1309, "text": "Small molecule CGRP receptor antagonists, gepants, are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (Eptinezumab, Fremanezumab, and Galcanezumab) or the CGRP receptor (Erenumab) effectively prevent migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30725283", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1773, "text": "vel classes of drugs, i.e., the 5-HT1F receptor agonists (lasmiditan) and the small molecule CGRP receptor antagonists (gepants). Data on the effects of 5-HT1F receptor agonism in relation to MOH, as well as the effects of chronic CGRP recepto", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31096904", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 659, "text": "small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine. Two of these an", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32799325", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "OBJECTIVE: Evaluate the safety and tolerability of oral rimegepant when used for acute treatment concomitantly with a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) ligand or receptor (CGRP mAb) for the preventive treatment of migraine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32799325", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 643, "text": "Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 1088, "text": "ithin the past decade. The commentary is supplemented by information presented in journal articles and focuses on the activity of several major pharmaceutical companies in the field.CONCLUSION: Two small molecule CGRP receptor antagonists, olcegepant and telcagepant, have been shown to be clinically efficacious in the treatment of migraine, and thus provide validation o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19939188", "endSection": "abstract" }, { "offsetInBeginSection": 1932, "offsetInEndSection": 2204, "text": "Recently, orally administered next-generation small molecule CGRP-RAs have been shown to have safety and efficacy in acute treatment (ubrogepant and rimegepant) and prevention (atogepant) of migraine, giving additional CGRP-based therapeutic options for migraine patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31020659", "endSection": "abstract" } ] }, { "body": "What are the two types of duplicated genes in the yeast S. cerevisiae?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28459980", "http://www.ncbi.nlm.nih.gov/pubmed/12836700", "http://www.ncbi.nlm.nih.gov/pubmed/15126414", "http://www.ncbi.nlm.nih.gov/pubmed/12594514", "http://www.ncbi.nlm.nih.gov/pubmed/25908670", "http://www.ncbi.nlm.nih.gov/pubmed/19594930", "http://www.ncbi.nlm.nih.gov/pubmed/18604285", "http://www.ncbi.nlm.nih.gov/pubmed/12902158", "http://www.ncbi.nlm.nih.gov/pubmed/27799339" ], "ideal_answer": [ "Yeast genes are duplicated both via the whole genome duplication and via smaller scale duplications. The genome of the budding yeast contains 50% of protein-coding genes that are paralogs, including 457 pairs of duplicated genes coming probably from an ancient whole genome duplication.", "The mechanism of duplication matters, with whole-genome duplicates being more transcriptionally altered than small-scale duplicates." ], "exact_answer": [ [ "whole-genome duplicates (WGD)" ], [ "small-scale duplicates (SSD)" ] ], "type": "list", "id": "5fdb43f6a43ad3127800002e", "snippets": [ { "offsetInBeginSection": 542, "offsetInEndSection": 673, "text": "We find high levels of redundancy among genes duplicated both via the whole genome duplication and via smaller scale duplications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18604285", "endSection": "abstract" }, { "offsetInBeginSection": 751, "offsetInEndSection": 971, "text": "Here, we present evidence from the Saccharomyces cerevisiae genome that a duplicate located in a genomic region with a low-recombination rate is likely to evolve faster than a duplicate in an area of high recombination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15126414", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 603, "text": "On the basis of the inferred phylogeny of each set of genes, we were able to deduce whether the gene duplicated and/or specialized before or after the divergence of two yeast lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12594514", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 792, "text": "gene duplications might have occurred as a single event, and that it probably took place before the Saccharomyces and Kluyveromyces lineages diverged from each other.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12594514", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 959, "text": "The mechanism of duplication matters, with whole-genome duplicates being more transcriptionally altered than small-scale duplicates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799339", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1015, "text": "The mechanism of duplication matters, with whole-genome duplicates exhibiting different preservation trends compared to small-scale duplicates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459980", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Whole-genome duplications (WGDs) have contributed to gene-repertoire enrichment in many eukaryotic lineages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25908670", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 427, "text": "Our genomic analysis on the yeast Saccharomyces cerevisiae shows that the number of shared regulatory motifs in the duplicates decreases with evolutionary time, whereas the total number of regulatory motifs remains unchanged.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12902158", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1176, "text": "The genome of the budding yeast contains 50% of protein-coding genes that are paralogs, including 457 pairs of duplicated genes coming probably from an ancient whole genome duplication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12836700", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 304, "text": "A whole-genome duplication occurred in the ancestor of Saccharomyces yeast species but 92% of duplicates returned to single-copy genes shortly after duplication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459980", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1014, "text": "The mechanism of duplication matters, with whole-genome duplicates exhibiting different preservation trends compared to small-scale duplicates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28459980", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 1075, "text": "iae genome. We partition the yeast duplicates into ohnologs (generated by a whole-genome duplication) and non-ohnologs (from small-scale duplication events) to determine whether their disparate origins commit them to divergent evolutionary trajectories and genomic attributes.RESULTS: We conclude that, for the most part, ohnologs tend to appear remarkably similar to non-ohnologs in their structural attributes (specifically the relative composition frequencies of complete, partial and chimeric duplicates), the discernible length of the duplicated region (duplication span) as well", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19594930", "endSection": "abstract" } ] }, { "body": "Why is fingolimod considered a prodrug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31110049" ], "ideal_answer": [ "FTY720/fingolimod, is considered a prodrug because it requires in vivo phosphorylation to its active phosphorylated form." ], "type": "summary", "id": "6053be3594d57fd879000019", "snippets": [ { "offsetInBeginSection": 318, "offsetInEndSection": 565, "text": "FTY720/fingolimod, a prodrug for the treatment of multiple sclerosis, is phosphorylated in vivo to its active phosphorylated form by sphingosine kinase 2 and has been shown to interfere with the actions of S1P and to inhibit ceramide biosynthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31110049", "endSection": "abstract" } ] }, { "body": "Is there a role for Dickkopf-1 (DKK1) in prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26913608", "http://www.ncbi.nlm.nih.gov/pubmed/17245340", "http://www.ncbi.nlm.nih.gov/pubmed/18687985", "http://www.ncbi.nlm.nih.gov/pubmed/33015525" ], "ideal_answer": [ "Yes. Dickkopf-1 (DKK1) expression is increased in double-negative prostate cancer (DNPC) relative to prostate-specific antigen (PSA)-expressing Metastatic castration-resistant prostate cancer (mCRPC).", "Yes, Dickkopf-1 (DKK-1) stimulated prostate cancer growth and metastasis and inhibited bone formation in osteoblastic bone metastases." ], "exact_answer": "yes", "type": "yesno", "id": "60206bae1cb411341a00007d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Dickkopf-1 Can Lead to Immune Evasion in Metastatic Castration-Resistant Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015525", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 2023, "text": "Metastatic castration-resistant prostate cancer (mCRPC) with low androgen receptor (AR) and without neuroendocrine signaling, termed double-negative prostate cancer (DNPC), is increasingly prevalent in patients treated with AR signaling inhibitors and is in need of new biomarkers and therapeutic targets.METHODS: Candidate genes enriched in DNPC were determined using differential gene expression analysis of discovery and validation cohorts of mCRPC biopsies. Laboratory studies were carried out in human mCRPC organoid cultures, prostate cancer (PCa) cell lines, and mouse xenograft models. Epigenetic studies were carried out in a rapid autopsy cohort.RESULTS: Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P < .0001). DKK1 expression can be regulated by activated Wnt signaling in vitro and correlates with activating canonical Wnt signaling mutations and low PSA mRNA in mCRPC biopsies (P < .05). DKK1 hypomethylation was associated with increased DKK1 mRNA expression (Pearson r = -0.66; P < .0001) in a rapid autopsy cohort (n = 7). DKK1-high mCRPC biopsies are infiltrated with significantly higher numbers of quiescent natural killer (NK) cells (P < .005) and lower numbers of activated NK cells (P < .0005). Growth inhibition of the human PCa model PC3 by the anti-DKK1 monoclonal antibody DKN-01 depends on the presence of NK cells in a severe combined immunodeficient xenograft mouse model.CONCLUSION: These results support DKK1 as a contributor to the immunosuppressive tumor microenvironment of DNPC. These data have provided the rationale for a clinical trial targeting DKK1 in mCRPC (ClinicalTrials.gov identifier: NCT03837353).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015525", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1238, "text": "DKK1 has been implicated in causing erosive arthritis, the osteolytic phenotypes of multiple myeloma and metastatic breast cancer, and osteoblastic metastases of prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687985", "endSection": "abstract" }, { "offsetInBeginSection": 715, "offsetInEndSection": 833, "text": "Dickkopf-1 protein secretion was documented in breast, prostate and lung cancer lines, but was negligible in melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17245340", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 1103, "text": "LTS: Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P < .0001). DK", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015525", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 1090, "text": "ckkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The Wnt inhibitor Dickkopf-1 (DKK-1) has been associated with the occurrence of bone metastases in osteotropic prostate cancer by inhibiting osteoblastogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26913608", "endSection": "abstract" }, { "offsetInBeginSection": 1193, "offsetInEndSection": 1329, "text": "These results reveal that p38 MAPK regulates DKK-1 in prostate cancer and may present a potential target in osteolytic prostate cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26913608", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 1073, "text": "xenograft models. Epigenetic studies were carried out in a rapid autopsy cohort.RESULTS: Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per millio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015525", "endSection": "abstract" } ] }, { "body": "What is Hemophilic Pseudotumor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25290383", "http://www.ncbi.nlm.nih.gov/pubmed/25404776", "http://www.ncbi.nlm.nih.gov/pubmed/15454768", "http://www.ncbi.nlm.nih.gov/pubmed/18799938", "http://www.ncbi.nlm.nih.gov/pubmed/25629563", "http://www.ncbi.nlm.nih.gov/pubmed/23095268", "http://www.ncbi.nlm.nih.gov/pubmed/31725667", "http://www.ncbi.nlm.nih.gov/pubmed/25332621", "http://www.ncbi.nlm.nih.gov/pubmed/17721227", "http://www.ncbi.nlm.nih.gov/pubmed/18092253", "http://www.ncbi.nlm.nih.gov/pubmed/20460342", "http://www.ncbi.nlm.nih.gov/pubmed/1395299", "http://www.ncbi.nlm.nih.gov/pubmed/8938781", "http://www.ncbi.nlm.nih.gov/pubmed/27615056", "http://www.ncbi.nlm.nih.gov/pubmed/32700372", "http://www.ncbi.nlm.nih.gov/pubmed/32530103", "http://www.ncbi.nlm.nih.gov/pubmed/16721483", "http://www.ncbi.nlm.nih.gov/pubmed/33083429", "http://www.ncbi.nlm.nih.gov/pubmed/32490041", "http://www.ncbi.nlm.nih.gov/pubmed/18284939", "http://www.ncbi.nlm.nih.gov/pubmed/24942018", "http://www.ncbi.nlm.nih.gov/pubmed/18836937", "http://www.ncbi.nlm.nih.gov/pubmed/8819627", "http://www.ncbi.nlm.nih.gov/pubmed/29095073", "http://www.ncbi.nlm.nih.gov/pubmed/20671836", "http://www.ncbi.nlm.nih.gov/pubmed/25006951", "http://www.ncbi.nlm.nih.gov/pubmed/2093257", "http://www.ncbi.nlm.nih.gov/pubmed/8246062", "http://www.ncbi.nlm.nih.gov/pubmed/28211222", "http://www.ncbi.nlm.nih.gov/pubmed/16296204", "http://www.ncbi.nlm.nih.gov/pubmed/28590380", "http://www.ncbi.nlm.nih.gov/pubmed/28852852", "http://www.ncbi.nlm.nih.gov/pubmed/26000180", "http://www.ncbi.nlm.nih.gov/pubmed/15662330", "http://www.ncbi.nlm.nih.gov/pubmed/17306128", "http://www.ncbi.nlm.nih.gov/pubmed/31970256", "http://www.ncbi.nlm.nih.gov/pubmed/22677741" ], "ideal_answer": [ "Hemophilic Pseudotumor is a rare complication of hemophilia. It is an encapsulated haematoma in patients with haemophilia which has a tendency to progress and produce clinical symptoms related to its anatomical location. The lesion most frequently occurs in the long bones, pelvis, small bones of the hands and feet, or rarely in the maxillofacial region." ], "type": "summary", "id": "60249aa31cb411341a0000a0", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Prevention is essential for avoiding the complications of muscle hematomas (pseudotumors, compartment syndromes and peripheral nerve lesions) in hemophilic patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32490041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "INTRODUCTION: Haemophilic pseudotumour (HP) is an encapsulated haematoma in patients with haemophilia (PWH) which has a tendency to progress and produce clinical symptoms related to its anatomical location.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32530103", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "AIMS: Haemophilic pseudotumor (HPT) is a rare but challenging complication of haemophilia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32700372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND: Hemophilic pseudotumor (HP) is a rare complication in patients with hemophilia. The lesion most frequently occurs in the long bones, pelvis, small bones of the hands and feet, or rarely in the maxillofacial region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33083429", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "AIM: Hemophilic pseudotumors result from repeated episodes of bleeding into bone, subperiosteum, and soft tissue. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29095073", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 259, "text": "An inadequate treatment of that bleeding in hemophilia may result in pseudotumor, usually in the muscle adjacent to the bone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "INTRODUCTION: Hemophilic pseudotumor is a rare complication occurring in patients with hemophilia, frequently seen in the femur, tibia, pelvic bones, iliac bones, or rarely in the maxillofacial region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Hemophilic pseudotumor is a rare complication, even in patients with severe hemophilia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28211222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The iliac hemophilic pseudotumor is a rare complication of hemophilia occurring in 1-2% of patients with Factor VIII or Factor IX deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1395299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Hemophilic pseudotumor is a rare but well-known complication of hemophilia manifesting as recurrent hemorrhage and progressive enlargement of hematoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006951", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1118, "text": "Cranial hemophilic pseudotumor is extremely rare, and with adequate factor-deficient replacement therapy, surgical management is a safe and effective way for cranial hemophilic pseudotumor treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Hemophilic pseudotumor is a rare, but well-known, complication of hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15662330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Hemophilic pseudotumor is a rare complication of hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17721227", "endSection": "abstract" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1575, "text": "Surgery is an effective treatment for hemophilic pseudotumor complicated by destructive osteoarthropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25629563", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "OBJECTIVE AND IMPORTANCE: Hemophilic pseudotumor is a rare complication of hemophilia, occurring in 1 to 2% of patients with severe hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8938781", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 223, "text": "An unusual case of a pediatric hemophilic pseudotumor of the paranasal sinus in a previously undiagnosed hemophiliac is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15454768", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1115, "text": "USSION: Hemophilic pseudotumor is rarely seen in patients with hemophilia, and even less frequently in patients without. Tra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27615056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "INTRODUCTION: Hemophilic pseudotumor is a rare but well documented complication seen in approximately 1-2% of patients with hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27615056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Hemophilic pseudotumor is a rare, but well-known, complication of hemophilia occurring in 1-2\u00a0% of individuals with a severe factor VIII or IX deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332621", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 373, "text": "The hemophilic pseudotumor is defined as an encapsulated hematoma that increases of volume progressively by episodes of recurrent hemorrhage; usually originate in soft tissues or in subperiosteal or intraosseous areas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "BACKGROUND: Hemophilic pseudotumor is an unusual complication occurring in only 1% to 2% of patients with severe factor VIII or IX deficiency, and manifests as a progressive enlargement of hematoma by recurrent hemorrhage, often resulting in bone destruction or resorption due to the chronic pressure of osseous hemo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18284939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "INTRODUCTION: Hemophilic pseudotumor is a rare complication occurring in patients with hemophilia, frequently seen in the femur, tibia, pelvic bones, iliac bones, or rarely in the maxillofacial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28852852", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 265, "text": "emophilic pseudotumor is a rare complication occurring in 1-2% of hemophiliacs and affecting mainly patients with severe disease or those who have developed antibodies to factor VIII or IX. A n", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17306128", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Hemophilic pseudotumor is an uncommon complication of factor VIII and IX deficiencies in the coagulation cascade and occurs in a wide spectrum of bones and soft tissues. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20671836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Hemophilic pseudotumor is an encapsulated, chronic, slowly expanding hematoma usually seen in 1-2% patients with severe coagulative disorder (James et al., 2003). It usu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18836937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Hemophilic pseudotumor is a rare, but well-known, complication of hemophilia occurring in 1-2\u00a0% of individuals with a severe factor VIII or IX deficiency. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Hemophilic pseudotumor is a rare complication of hemophilia, occurring in 1 to 2 percent of individuals with severe factor VIII or factor IX deficiency. A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26000180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Hemophilic pseudotumor is a rare but well-known complication of hemophilia manifesting as recurrent hemorrhage and progressive enlargement of hematoma. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Hemophilic pseudotumor is a rare complication of hemophilia occurring in 1% to 2% of individuals with a severe factor VIII or IX deficiency. Thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8246062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The iliac hemophilic pseudotumor is a rare complication of hemophilia occurring in 1-2% of patients with Factor VIII or Factor IX deficiency. It", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1395299", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 309, "text": "We describe a 50-year-old man with mild hemophilia A, but with no previous need for Factor VIII supplementation, who presented with a pathologic fracture of the right femoral neck and shaft caused by a large hemophilic pseudotumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15662330", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 863, "text": "Although pseudotumor formation is a well-recognized complication of hemophilia, the pseudotumor in our study is one of the largest yet described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15662330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "INTRODUCTION: Hemophilic pseudotumor is a rare but well documented complication seen in approximately 1-2% of patients with hemophilia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27615056", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1114, "text": "USSION: Hemophilic pseudotumor is rarely seen in patients with hemophilia, and even less frequently in patients without. Tr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27615056", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 530, "text": "The objective of this article is to report surgical treatment and follow-up outcomes of three unusual cases with giant abdominal hemophilic pseudotumor.We describe 3 patients with giant hemophilic pseudotumor involving the abdomen who were successfully treated with tumor resection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31725667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Hemophilic pseudotumor is a rare lesion that is essentially a progressive, slowly expanding, encapsulated hematoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22677741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Hemophilic pseudotumor has been defined as a progressive cystic swelling involving muscle which is produced by recurrent hemorrhage and accompanied by roentgenographic evidence of bone involvement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2093257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The haemophilic pseudotumor is defined as an encased hematoma that increases of volume progressively by episodes of recurrent hemorrhage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16721483", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Hemophilic pseudotumor is a rare complication of hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24942018", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "OBJECTIVE AND IMPORTANCE: Hemophilic pseudotumor is a rare complication of hemophilia, occurring in 1 to 2% of patien", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8938781", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 694, "text": "Hemophilic pseudotumors are rare complications occurring in 1-2% of patients with mild or severe hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095268", "endSection": "abstract" }, { "offsetInBeginSection": 49, "offsetInEndSection": 231, "text": "Hemophilic pseudotumor results from multiple episodes of hemorrhage into bones or soft tissue spaces. It is uncommon and is seen in severe cases of hemophilia only 1-2% of the time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16296204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Hemophilic pseudotumor is an uncommon complication seen in approximately 1-2% of patients with severe hemophilia. Hemophilic pseudotumors are distinguished into two subdivisions based on location, proximal or distal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18092253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Pseudotumor is an uncommon but severe complication in patients with hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20460342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Hemophilic pseudotumor is one of the most serious complications of hemophilia and is usually treated with extensive surgery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8819627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "INTRODUCTION: Hemophilic pseudotumor is a rare complication that occurs in patients with severe hemophilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25290383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Hemophilic pseudotumors are rare, but well known complications of severe hemophilia A, which most frequently develops at the femur, tibia, pelvic bones, iliac bones, or rarely in the cranium or gnathic bones.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18799938", "endSection": "abstract" } ] }, { "body": "What is the aim of the TRAP method?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31354448", "http://www.ncbi.nlm.nih.gov/pubmed/28648677", "http://www.ncbi.nlm.nih.gov/pubmed/32478741" ], "ideal_answer": [ "The translating ribosome affinity purification (TRAP) method is used to obtain obtain translatome data." ], "type": "summary", "id": "6081b9d64e6a4cf63000000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "In this article, we give hands-on instructions to obtain translatome data from different Arabidopsis thaliana root cell types via the translating ribosome affinity purification (TRAP) method ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32478741", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1427, "text": " Using translating ribosome affinity purification (TRAP) method to isolate CA3 translating mRNAs,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31354448", "endSection": "abstract" }, { "offsetInBeginSection": 631, "offsetInEndSection": 819, "text": "we describe the use of the Translating Ribosome Affinity Purification (TRAP) method for C. elegans to detect cell type-specific gene expression patterns at the level of translating mRNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28648677", "endSection": "abstract" } ] }, { "body": "The Shingrix vaccine is used to prevent what disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32999027", "http://www.ncbi.nlm.nih.gov/pubmed/31399377", "http://www.ncbi.nlm.nih.gov/pubmed/33067034", "http://www.ncbi.nlm.nih.gov/pubmed/31423396", "http://www.ncbi.nlm.nih.gov/pubmed/30145235", "http://www.ncbi.nlm.nih.gov/pubmed/33163688", "http://www.ncbi.nlm.nih.gov/pubmed/32862397", "http://www.ncbi.nlm.nih.gov/pubmed/31258310", "http://www.ncbi.nlm.nih.gov/pubmed/30370455", "http://www.ncbi.nlm.nih.gov/pubmed/32606264", "http://www.ncbi.nlm.nih.gov/pubmed/31400911" ], "ideal_answer": [ "Shingrix is a 4-component vaccine against capsular herpes zoster (4CZV), which has recently been licensed in Europe, Canada and Australia.", "the shingrix vaccine is used for the prevention of herpes zoster and postherpetic neuralgia.", "Shingrix vaccine is used for prevention of herpes zoster.", "The Shingrix vaccine is used for prevention of herpes zoster.", "The Shingrix vaccine prevents Postherpetic neuralgia, also known as Shingles, which is caused by herpes zoster (HZ)" ], "exact_answer": [ "Postherpetic neuralgia, also known as Shingles", "herpes zooster" ], "type": "factoid", "id": "601c17c21cb411341a00000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 514, "text": "Postherpetic neuralgia (PHN) is a challenging condition for pain management specialists. The prevention of herpes zoster (HZ) and subsequent PHN in individuals aged 50 years and older, via the development of new vaccines, is an ongoing research project. The live zoster vaccine (LZV, Zostavax\u00ae) was the first proof of concept that vaccination could prevent HZ, but LZV cannot be used in various immunecompromised patients. This led to the development of a new non-live recombinant zoster vaccine (RZV, Shingrix\u00ae). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32606264", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 318, "text": " Previously, secondary prevention of herpes zoster required live-attenuated vaccination, which is contraindicated in immunocompromised populations. More recently, a recombinant subunit vaccine (Shingrix, GlaxoSmithKline, Research Triangle Park, North Carolina) was approved by the Food and Drug Administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33163688", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 383, "text": "SHINGRIX, a non-live recombinant herpes zoster vaccine, was approved by the Food and Drug Administration in 2017.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33067034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Recombinant Zoster Vaccine (Shingrix) to Prevent Herpes Zoster.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145235", "endSection": "title" }, { "offsetInBeginSection": 250, "offsetInEndSection": 436, "text": "Two different vaccines have been developed to prevent HZ; one is based on a live attenuated VZV strain (Zostavax), and the other is based on adjuvanted gE recombinant protein (Shingrix).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32999027", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 718, "text": "Shingrix is a new attenuated subunit vaccine for Varicella Zoster Virus with an AS01B adjuvant that can result in a potent immune response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423396", "endSection": "abstract" }, { "offsetInBeginSection": 545, "offsetInEndSection": 691, "text": "In October 2017, the U.S. Food and Drug Administration approved recombinant zoster vaccine under the brand name Shingrix to prevent herpes zoster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "BACKGROUND: The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31399377", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 537, "text": "ctober 2017, the US Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommended the adjuvanted recombinant zoster vaccine (RZV; Shingrix, GSK) as the preferred vaccine for preventing herpes zoster (HZ) and related complications in immunocompetent adults aged \u2265\u00a050 years. Subsequentl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32862397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Zoster vaccine live (ZVL [Zostavax]) has been recommended for the prevention of herpes zoster (HZ) among immunocompetent adults \u226560\u202fyears in the United States since 2008. To exa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31400911", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 343, "text": " The subunit vaccine is approved for the prevention of herpes zoster (HZ) [EU, USA, Japan, Canada and Australia] and postherpetic neuralgia (PHN) [EU and Australia] in adults aged\u2009\u2265\u200950\u00a0years. In the pivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30370455", "endSection": "abstract" }, { "offsetInBeginSection": 586, "offsetInEndSection": 726, "text": "x is a new attenuated subunit vaccine for Varicella Zoster Virus with an AS01B adjuvant that can result in a potent immune response. The Shi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31423396", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 534, "text": "ctober 2017, the US Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommended the adjuvanted recombinant zoster vaccine (RZV; Shingrix, GSK) as the preferred vaccine for preventing herpes zoster (HZ) and related complications in immunocompetent adults aged \u2265\u00a050 years. Subseque", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32862397", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 340, "text": " The subunit vaccine is approved for the prevention of herpes zoster (HZ) [EU, USA, Japan, Canada and Australia] and postherpetic neuralgia (PHN) [EU and Australia] in adults aged\u2009\u2265\u200950\u00a0years. In the p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30370455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Zoster vaccine live (ZVL [Zostavax]) has been recommended for the prevention of herpes zoster (HZ) among immunocompetent adults \u226560\u202fyears in the United States since 2008. To ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31400911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Women ages 50 years and older are at risk for herpes zoster, a reactivated virus from varicella zoster virus (chickenpox) that causes a painful vesicular rash and can result in postherpetic neuralgia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30145235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND: The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31399377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Shingrix, a new vaccine for herpes zoster.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31258310", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Shingrix: A New Herpes Zoster Vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31258310", "endSection": "title" } ] }, { "body": "What is the function of HP1a in the nucleus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19798443", "http://www.ncbi.nlm.nih.gov/pubmed/29728561", "http://www.ncbi.nlm.nih.gov/pubmed/30659116", "http://www.ncbi.nlm.nih.gov/pubmed/22547675", "http://www.ncbi.nlm.nih.gov/pubmed/24782529", "http://www.ncbi.nlm.nih.gov/pubmed/24555990", "http://www.ncbi.nlm.nih.gov/pubmed/30384843", "http://www.ncbi.nlm.nih.gov/pubmed/24637637", "http://www.ncbi.nlm.nih.gov/pubmed/25945750", "http://www.ncbi.nlm.nih.gov/pubmed/28688038", "http://www.ncbi.nlm.nih.gov/pubmed/23476027", "http://www.ncbi.nlm.nih.gov/pubmed/28636597", "http://www.ncbi.nlm.nih.gov/pubmed/29358235", "http://www.ncbi.nlm.nih.gov/pubmed/11259603", "http://www.ncbi.nlm.nih.gov/pubmed/30442760", "http://www.ncbi.nlm.nih.gov/pubmed/23894480", "http://www.ncbi.nlm.nih.gov/pubmed/24681131" ], "ideal_answer": [ "Heterochromatin protein 1 (HP1) is an abundant component of heterochromatin, a highly condensed compartment of the nucleus that comprises a major fraction of complex genomes.", "Drosophila heterochromatin-associated protein 1 (HP1) is an abundant component of heterochromatin, a highly condensed compartment of the nucleus that comprises a major fraction of complex genomes.", "Heterochromatin protein 1 (HP1) was first described in Drosophila melanogaster as a heterochromatin associated protein required for epigenetic gene silencing." ], "type": "summary", "id": "5eb504560d431b5f7300000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Drosophila heterochromatin-associated protein 1 (HP1) is an abundant component of heterochromatin, a highly condensed compartment of the nucleus that comprises a major fraction of complex genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11259603", "endSection": "abstract" }, { "offsetInBeginSection": 1025, "offsetInEndSection": 1193, "text": "Both the HP1a hinge and chromo shadow domain independently target heterochromatin, while the HP1c chromo shadow domain is implicated solely in euchromatin localization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11259603", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 418, "text": "Recently, Drosophila melanogaster Piwi was recently reported to associate with chromatin and to interact directly with the Heterochromatin Protein 1 (HP1a)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24637637", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1018, "text": "These results suggest that silkworm Piwi proteins function as a chromatin regulator in collaboration with HP1a and HP1b.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24637637", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 170, "text": "Heterochromatin protein 1 (HP1) was first described in Drosophila melanogaster as a heterochromatin associated protein required for epigenetic gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24681131", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 664, "text": "Here we characterized the genome-wide effect of nuclear Piwi elimination on the presence of the heterochromatic H3K9me3 mark and HP1a, as well as on the transcription-associated mark H3K4me2. Our results demonstrate that a significant increase in the H3K4me2 level upon nuclear Piwi loss is not accompanied by the alterations in H3K9me3 and HP1a levels for several germline-expressed transposons, suggesting that in this case Piwi prevents transcription by a mechanism distinct from H3K9 methylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24782529", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 411, "text": "Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28636597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The large fraction of heterochromatin in Drosophila neurons is bound by both B-type lamin and HP1a.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30384843", "endSection": "title" }, { "offsetInBeginSection": 279, "offsetInEndSection": 484, "text": "However, in Kc167 cell culture, the only Drosophilla cell type where LADs have previously been mapped, they are neither H3K9me2-enriched nor overlapped with the domains of heterochromatin protein 1a (HP1a)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30384843", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 933, "text": "Strikingly, contrary to Kc167 cells of embryonic origin, in neurons and, to a lesser extent, in glia and the fat body, HP1a domains appear to overlap strongly with LADs in both the chromosome arms and pericentromeric regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30384843", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 282, "text": "Heterochromatin protein 1a (HP1a) has been proposed to function downstream of Piwi-piRNA complex in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29728561", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1030, "text": "The chromatin of all transgene-associated piRNA clusters contain high levels of trimethylated lysine 9 of histone H3 (H3K9me3) and HP1a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358235", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 429, "text": "Su(var) 3-9 protein was found to be localized in the nucleus in Sf9 cells, and interact with histone H3, and the heterochromatin protein 1a (HP1a) and HP1b.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894480", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 243, "text": "An important component of the telomeres is the heterochromatin protein 1a (HP1a).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28688038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Heterochromatin protein 1a (HP1a) is a chromatin-associated protein important for the formation and maintenance of heterochromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23476027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Drosophila heterochromatin-associated protein 1 (HP1) is an abundant component of heterochromatin, a highly condensed compartment of the nucleus that comprises a major fraction of complex genomes. S", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11259603", "endSection": "abstract" }, { "offsetInBeginSection": 1140, "offsetInEndSection": 1363, "text": "ophila HP1a protein undergoes liquid-liquid demixing in vitro, and nucleates into foci that display liquid properties during the first stages of heterochromatin domain formation in early Drosophila embryos. Furthermore, in ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28636597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Expression of transposable elements in the germline is controlled by Piwi-interacting (pi) RNAs produced by genomic loci termed piRNA clusters and associated with Rhino, a heterochromatin protein 1 (HP1) homolog. Pre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29358235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Heterochromatin protein 1 (HP1) is an epigenetic regulator of chromatin structure and genome function in eukaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30659116", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 443, "text": "9 protein was found to be localized in the nucleus in Sf9 cells, and interact with histone H3, and the heterochromatin protein 1a (HP1a) and HP1b. A dose-depend", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Heterochromatin protein 1a (HP1a) is a highly conserved and versatile epigenetic factor that can both silence and activate transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30442760", "endSection": "abstract" }, { "offsetInBeginSection": 256, "offsetInEndSection": 342, "text": "Here, we show that Eyg forms a protein complex with heterochromatin protein 1a (HP1a).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22547675", "endSection": "abstract" }, { "offsetInBeginSection": 1713, "offsetInEndSection": 1813, "text": "The recruitment of HP1a prevents transcription by favoring a closed, heterochromatin-like structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22547675", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1142, "text": "Using position effect variegation (PEV) experiments, we demonstrated that eyg has a dose-dependent effect on heterochromatin gene silencing and identified a genetic interaction with HP1a in this process.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22547675", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 543, "text": "HP1a is an evolutionarily conserved heterochromatin-associated protein, which plays an essential role in heterochromatin-mediated gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25945750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Heterochromatin Protein 1 (HP1a) is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19798443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Heterochromatin protein 1 (HP1a in Drosophila) is a conserved eukaryotic chromosomal protein that is prominently associated with pericentric heterochromatin and mediates the concomitant gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Heterochromatin protein 1a functions for piRNA biogenesis predominantly from pericentric and telomeric regions in Drosophila.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29728561", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Heterochromatin protein 1 (HP1) is an epigenetic regulator of chromatin structure and genome function in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30659116", "endSection": "abstract" } ] }, { "body": "Has AZD9668 been tested in clinical trials?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22458939", "http://www.ncbi.nlm.nih.gov/pubmed/26043724" ], "ideal_answer": [ "Yes, AZD9668 has been tested in clinical trials." ], "exact_answer": "yes", "type": "yesno", "id": "602c28551cb411341a000123", "snippets": [ { "offsetInBeginSection": 152, "offsetInEndSection": 450, "text": "Efficacy, safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb trial (NCT00949975: approved by an Investigational Review Board), in patients with symptomatic COPD receiving maintenance tiotropium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22458939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22458939", "endSection": "title" } ] }, { "body": "Which class of genomic elements was assessed as part of the FANTOM6 project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32718982", "http://www.ncbi.nlm.nih.gov/pubmed/33211864" ], "ideal_answer": [ "Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, the expression of 285 lncRNAs was systematically knocked down in human dermal fibroblasts. Cellular growth, morphological changes, and transcriptomic responses were quantified using Capped Analysis of Gene Expression (CAGE).", "The functional annotation of the mammalian genome 6 (FANTOM6) project aims to systematically map all human long noncoding RNAs (lncRNAs) in a gene-dependent manner through dedicated efforts from national and international teams" ], "exact_answer": [ "Long noncoding RNAs", "lncRNAs" ], "type": "factoid", "id": "602a84ae1cb411341a000116", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 872, "text": "Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32718982", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 397, "text": "As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32718982", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 1014, "text": "From its creation until 2020, FANTOM6 has contributed to the research community a large dataset generated from the knock-down of 285 lncRNAs in human dermal fibroblasts; this is followed with extensive expression profiling and cellular phenotyping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33211864", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 765, "text": "The sixth (latest) edition of the FANTOM project was launched to assess the function of human long non-coding RNAs (lncRNAs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33211864", "endSection": "abstract" }, { "offsetInBeginSection": 784, "offsetInEndSection": 1032, "text": "until 2020, FANTOM6 has contributed to the research community a large dataset generated from the knock-down of 285 lncRNAs in human dermal fibroblasts; this is followed with extensive expression profiling and cellular phenotyping. Other updates to ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33211864", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 404, "text": "rt of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antise", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32718982", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by Camrelizumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31939447", "http://www.ncbi.nlm.nih.gov/pubmed/31939448", "http://www.ncbi.nlm.nih.gov/pubmed/30213452", "http://www.ncbi.nlm.nih.gov/pubmed/32112738", "http://www.ncbi.nlm.nih.gov/pubmed/32416073", "http://www.ncbi.nlm.nih.gov/pubmed/32499235", "http://www.ncbi.nlm.nih.gov/pubmed/31017739", "http://www.ncbi.nlm.nih.gov/pubmed/32376724", "http://www.ncbi.nlm.nih.gov/pubmed/33004770", "http://www.ncbi.nlm.nih.gov/pubmed/32256049", "http://www.ncbi.nlm.nih.gov/pubmed/32623573", "http://www.ncbi.nlm.nih.gov/pubmed/32602470", "http://www.ncbi.nlm.nih.gov/pubmed/32411597", "http://www.ncbi.nlm.nih.gov/pubmed/33087333", "http://www.ncbi.nlm.nih.gov/pubmed/32762583", "http://www.ncbi.nlm.nih.gov/pubmed/31420358", "http://www.ncbi.nlm.nih.gov/pubmed/33154554", "http://www.ncbi.nlm.nih.gov/pubmed/31238988", "http://www.ncbi.nlm.nih.gov/pubmed/33299330", "http://www.ncbi.nlm.nih.gov/pubmed/30242068", "http://www.ncbi.nlm.nih.gov/pubmed/31313098", "http://www.ncbi.nlm.nih.gov/pubmed/31039052", "http://www.ncbi.nlm.nih.gov/pubmed/32776600", "http://www.ncbi.nlm.nih.gov/pubmed/33092443", "http://www.ncbi.nlm.nih.gov/pubmed/33097476", "http://www.ncbi.nlm.nih.gov/pubmed/33241036", "http://www.ncbi.nlm.nih.gov/pubmed/32064977", "http://www.ncbi.nlm.nih.gov/pubmed/32530632", "http://www.ncbi.nlm.nih.gov/pubmed/33063473", "http://www.ncbi.nlm.nih.gov/pubmed/33194624", "http://www.ncbi.nlm.nih.gov/pubmed/33052760" ], "ideal_answer": [ "Camrelizumab is a humanised antibody that targets programmed death-1 (PD-1) ligand.", "Camrelizumab is PD-1 (programmed cell death-1 receptor) inhibitor that is used for treatment of cancer." ], "exact_answer": [ "PD-1", "programmed death-1" ], "type": "factoid", "id": "602828b11cb411341a0000fc", "snippets": [ { "offsetInBeginSection": 333, "offsetInEndSection": 417, "text": "Camrelizumab (SHR-1210) is a humanised anti-programmed death-1 (anti PD-1) antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "The PD-1 antibody camrelizumab was well tolerated in patients with nasopharyngeal carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30242068", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 400, "text": "As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31039052", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 416, "text": "Camrelizumab (SHR-1210) is a humanised anti-programmed death-1 (anti PD-1) antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213452", "endSection": "abstract" }, { "offsetInBeginSection": 1943, "offsetInEndSection": 2055, "text": "Decitabine plus camrelizumab may reverse resistance to PD-1 inhibitors in patients with relapsed/refractory cHL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31039052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31039052", "endSection": "title" }, { "offsetInBeginSection": 1751, "offsetInEndSection": 1942, "text": "CONCLUSION CR rate in patients with relapsed/refractory cHL who were clinically na\u00efve to PD-1 blockade was significantly higher with decitabine plus camrelizumab than with camrelizumab alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31039052", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 399, "text": "As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31039052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Recent phase 1-2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31238988", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 417, "text": "Camrelizumab (SHR-1210) is a humanised anti-programmed death-1 (anti PD-1) antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30213452", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 400, "text": "As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31039052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Recent phase 1-2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31238988", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1622, "text": "Here, we represent preliminary evidence for the comparative safety and efficacy of existing anti-PD-1 agents with/without chemotherapy in RM-NPC, which indicated that camrelizumab has the least toxicity profile and merits future investigation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31238988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Camrelizumab (AiRuiKa\u2122), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31313098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR-1210), a novel anti-PD-1 antibody.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31017739", "endSection": "title" }, { "offsetInBeginSection": 363, "offsetInEndSection": 611, "text": "All patients were administered intravenous camrelizumab (SHR-1210), a novel anti-PD-1 antibody, at doses of 60 mg, 200 mg, or 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31017739", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 558, "text": "Here we describe a case of a novel pattern of RRP induced by anti-PD-1 blockade Camrelizumab 2 years after radiotherapy, with some focus on further understanding of this phenomenon. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32411597", "endSection": "abstract" }, { "offsetInBeginSection": 842, "offsetInEndSection": 1022, "text": "After 15 months, due to tumor progression and brain metastasis, he started with administration of anti-PD-1 blockade Camrelizumab (200 mg q2w) and stereotactic radiosurgery (SRS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32411597", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 311, "text": "We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32416073", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 303, "text": "This study aimed to assess the antitumour activity and safety of the anti-PD-1 inhibitor camrelizumab in pretreated patients with advanced hepatocellular carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32112738", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 789, "text": "In our present report, we described a newly diagnosed non-small-cell lung cancer\u00a0patient who suffered from focal vitiligo for approximately ten\u00a0years and was treated with the anti-programmed cell death-1 receptor\u00a0antibody camrelizumab (SHR-1210), which accelerated the aggravation of depigmentation of the skin over the whole body in just half a year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32064977", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 497, "text": "PATIENTS AND METHODS: In this open-label, single-arm, phase II study, the safety and efficacy of combined regimen of chemotherapy consisting of gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) plus anti-PD-1 antibody camrelizumab was assessed in rrPMBCL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32499235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32376724", "endSection": "title" }, { "offsetInBeginSection": 695, "offsetInEndSection": 957, "text": "We further benchmarked the dissociation kinetics for three clinically approved PD-1 blockade mAbs (Nivolumab, Pembrolizumab, and Camrelizumab), intriguingly correlating well with the objective response rates in the hepatocellular carcinoma second-line treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32530632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Purpose: Camrelizumab inhibits PD-1 in non-clinical models and showed typical non-clinical pharmacokinetic (PK) and safety profiles for an IgG4 monoclonal antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32256049", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 184, "text": "Camrelizumab is a programmed cell death protein 1 inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33092443", "endSection": "abstract" }, { "offsetInBeginSection": 1433, "offsetInEndSection": 1700, "text": "sions: Our findings suggest that (I) PD-1 targeted immunotherapy with toripalimab, camrelizumab, or sintilimab yielded a promising outcome in Chinese HBV patients with HCC and that (II) immunotherapy was well tolerated generally and had manageable side effects. This ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33241036", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 486, "text": "ately, the tumors dramatically shrank after one cycle of camrelizumab, an anti-programmed cell death-1 (PD-1) antibody developed by Chinese Hengrui Medicine. In concl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33299330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "We report a case of a 68-year-old man diagnosed with pulmonary pleomorphic carcinoma who showed partial response after a single treatment with camrelizumab (PD1 monoclonal antibody)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33299330", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 421, "text": "JECTIVE: To evaluate the immune-related adverse events (irAEs) induced by Camrelizumab, an anti-PD-1 antibody in a patient with gastric cancer.C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32602470", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 957, "text": "RT OPINION: Camrelizumab is a selective, humanized, high-affinity IgG4 kappa mAb against PD-1. Ca", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32762583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "INTRODUCTION: Camrelizumab (also known as SHR-1210), a humanized monoclonal antibody against PD-1, has been shown to block the binding of PD-1 to PD-L1 and consequently inhibit the immune escape of tumor cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32762583", "endSection": "abstract" }, { "offsetInBeginSection": 694, "offsetInEndSection": 887, "text": "The structure of the camrelizumab/PD-1 complex reveals that camrelizumab mainly utilizes its heavy chain to bind to PD-1, while the light chain sterically inhibits the binding of PD-L1 to PD-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063473", "endSection": "abstract" }, { "offsetInBeginSection": 438, "offsetInEndSection": 693, "text": "Here, we demonstrate varied N-glycan composition in PD-1, and show that the binding affinity of camrelizumab, a recently approved PD-1-specific MAb, to non-glycosylated PD-1 proteins from E.\u00a0coli is substantially decreased compared with glycosylated PD-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063473", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 304, "text": "This study aimed to assess the antitumour activity and safety of the anti-PD-1 inhibitor camrelizumab in pretreated patients with advanced hepatocellular carcinoma.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32112738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "INTRODUCTION: Camrelizumab (also known as SHR-1210), a humanized monoclonal antibody against PD-1, has been shown to block the binding of PD-1 to PD-L1 and consequently inhibit the immune escape o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32762583", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Purpose: Camrelizumab inhibits PD-1 in non-clinical models and showed typical non-clinical pharmacokinetic (PK) and safety profiles for an IgG4 monoclonal ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32256049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Camrelizumab (AiRuiKa\u2122), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31313098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The PD-1 antibody camrelizumab plus the VEGFR2 inhibitor apatinib had efficacy in a phase II trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33097476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "PURPOSE: We assessed the efficacy and safety of camrelizumab (an anti-PD-1 monoclonal antibody) plus apatinib (a vascular endothelial growth factor [VEGFR]-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33087333", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 968, "text": "However, all three patients responded to low-dose decitabine, an epigenetic drug, in combination with camrelizumab (anti-PD-1 antibody), with only controllable adverse events, indicating that low-dose decitabine can sensitize PD-1/PD-L1 inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33194624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Background: Camrelizumab is a promising anti-programmed cell death-1 agent for non-small cell lung cancer (NSCLC) and induces reactive capillary hemangiomas (RCHs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31939447", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 356, "text": "Camrelizumab is a programmed cell death protein 1 inhibitor; however, current evidence of its efficacy in PSC is lacking.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32776600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Camrelizumab is a programmed death receptor-1 inhibitor originally developed in China for the treatment of refractory lymphoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33004770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 315, "text": "Recent phase 1-2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31238988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma, nasopharyngeal cancer and non-small cell lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33154554", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "PURPOSE: Camrelizumab is an antibody against programmed death protein 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33052760", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 632, "text": "All patients were administered intravenous camrelizumab (SHR-1210), a novel anti-PD-1 antibody, at doses of 60 mg, 200 mg, or 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31017739", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 333, "text": "Therefore, we explored the efficacy and safety of a PD-1 checkpoint inhibitor camrelizumab in advanced or metastatic solid tumour with dMMR/MSI-H.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32623573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Aim: The present study evaluated the safety and efficacy of camrelizumab (a programmed death-1 antibody) in combination with microwave ablation (MWA) in advanced non-small cell lung cancer (NSCLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31939448", "endSection": "abstract" } ] }, { "body": "What is a foam cell?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31945610", "http://www.ncbi.nlm.nih.gov/pubmed/31938053", "http://www.ncbi.nlm.nih.gov/pubmed/32012706", "http://www.ncbi.nlm.nih.gov/pubmed/31894855", "http://www.ncbi.nlm.nih.gov/pubmed/31909985", "http://www.ncbi.nlm.nih.gov/pubmed/31967154" ], "ideal_answer": [ "Foam cell, a hallmark of atherosclerosis, is prominently derived from monocyte-differentiated macrophage, and vascular smooth muscle cells (VSMCs) through unlimitedly phagocytizing oxidized low-density lipoprotein (oxLDL). Therefore, the inhibition of monocyte adhesion to endothelium and uptake of oxLDL might be a breakthrough point for retarding atherosclerosis." ], "exact_answer": [ "A foam cell is prominently derived from monocyte-differentiated macrophage, and vascular smooth muscle cells (VSMCs) through unlimitedly phagocytizing oxidized low-density lipoprotein (oxLDL)" ], "type": "factoid", "id": "6086f0ef4e6a4cf630000011", "snippets": [ { "offsetInBeginSection": 90, "offsetInEndSection": 455, "text": "Foam cell, a hallmark of atherosclerosis, is prominently derived from monocyte-differentiated macrophage, and vascular smooth muscle cells (VSMCs) through unlimitedly phagocytizing oxidized low-density lipoprotein (oxLDL). Therefore, the inhibition of monocyte adhesion to endothelium and uptake of oxLDL might be a breakthrough point for retarding atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31938053", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 199, "text": "Atherosclerosis (AS) is a chronic inflammatory disease that contributes to multiple cardiovascular diseases (CVDs), and foam cell formation plays important roles in the progression of AS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31894855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Oxidative stress, inflammation, and foam cell formation in vascular smooth muscle cells (VSMCs) are considered to play crucial roles in the pathogenesis of atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31945610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32012706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Lipid droplet (LD) accumulation, a key feature of foam cells, constitutes an attractive target for therapeutic intervention in atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31909985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Abnormal lipid metabolism in macrophages leads to atherosclerosis (AS). Excessive LDL cholesterol uptake by macrophages in the aortic endothelium leads to formation of foam cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31967154", "endSection": "abstract" } ] }, { "body": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17143099", "http://www.ncbi.nlm.nih.gov/pubmed/19940267", "http://www.ncbi.nlm.nih.gov/pubmed/20195425", "http://www.ncbi.nlm.nih.gov/pubmed/26402985", "http://www.ncbi.nlm.nih.gov/pubmed/27870723", "http://www.ncbi.nlm.nih.gov/pubmed/33194498", "http://www.ncbi.nlm.nih.gov/pubmed/17700359", "http://www.ncbi.nlm.nih.gov/pubmed/12426921", "http://www.ncbi.nlm.nih.gov/pubmed/16575599", "http://www.ncbi.nlm.nih.gov/pubmed/15849374", "http://www.ncbi.nlm.nih.gov/pubmed/11869826", "http://www.ncbi.nlm.nih.gov/pubmed/15269925" ], "ideal_answer": [ " Muscular complaints are known side-effects of statin therapy, ranging from myalgia to clinically important myositis and rhabdomyolysis.", "3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors (statins) are generally well tolerated, with statin-associated muscle symptoms (SAMS) the most common side effect (~10%) seen in statin users.", "The most commonly experienced side-effect of statin medication is muscle pain", "A class of drug called a statin. It's a drug that works by reducing the amount of cholesterol in the body, which is what causes muscle fatigue.", "statins are generally well tolerated, with statin-associated muscle symptoms (sams) the most common side effect (~10%) seen in statin users.", "Statin use has been associated with an increased risk of glucocorticoid-induced rhabdomyolysis as well as with adverse effects such as mysositis and hypercholesterolemia.", "3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors, a class of drugs called statins are generally well tolerated, with statin-associated muscle symptoms (SAMS) such as muscle pain, myositis, and rarely rhabdomyolysis, the most common side effect (~10%) seen in statin users." ], "exact_answer": [ "statins" ], "type": "factoid", "id": "601ff4a61cb411341a000076", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 223, "text": "3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors (statins) are generally well tolerated, with statin-associated muscle symptoms (SAMS) the most common side effect (~10%) seen in statin users.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27870723", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 148, "text": " Muscular complaints are known side-effects of statin therapy, ranging from myalgia to clinically important myositis and rhabdomyolysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26402985", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 256, "text": " the statin use and association with the presence and characteristics of muscular complaints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26402985", "endSection": "abstract" }, { "offsetInBeginSection": 1265, "offsetInEndSection": 1362, "text": "n the studied set of patients muscular symptoms were a rather frequent effect of statin therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26402985", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 635, "text": "yopathy is included among the potential side-effects and toxicities associated with the lipid lowering agents, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. However, the precise mechanism of statin-induced muscle toxicity remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15849374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Lipid lowering drugs, such as statins, are commonly used to treat approximately 10 million Canadians affected by hypercholesterolemia. The most commonly experienced side-effect of statin medication is muscle pain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20195425", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 333, "text": "Statin induced myopathy consists of a spectrum of myopathic disorders ranging from mild myalgia to fatal rhabdomyolysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20195425", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 417, "text": " The following is a presentation of 2 cases of statin induced myopathy in patients ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20195425", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 574, "text": "In addition, discussion will surround the mechanism, predisposing risk factors and frequency of statin induced myopathy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20195425", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 550, "text": "Rhabdomyolysis is a known, rare serious side effect of statin monotherapy and of statin-fibrate combination therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15269925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Statin use is associated with a variety of overtly related muscle symptoms including muscle pain, myalgia, creatine kinase elevations without pain with myolysis and myositis (rhabdomyolysis), a potentially fatal side effect that led to the withdrawal of cerivastatin in 2001.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17700359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "CYP2D6*4 polymorphism is associated with statin-induced muscle effects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17700359", "endSection": "title" }, { "offsetInBeginSection": 171, "offsetInEndSection": 276, "text": "Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19940267", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 333, "text": "Rhabdomyolysis is a rare but severe toxicity of statins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19940267", "endSection": "abstract" }, { "offsetInBeginSection": 959, "offsetInEndSection": 1135, "text": "The drugs which most frequently induce muscular side effects are steroids, statins, fibrates, antiretrovirals, immunosuppressants, colchicine, amiodarone, and anticancer drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575599", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Muscular side effects of various anesthetics, analgetics, antibiotics, antihistaminic drugs, antiretrovirals, cardiotropics, immunosuppressants, lipid-lowering drugs, psychotropic drugs, anticancer drugs, and other substances are more frequent than assumed and are easily overlooked.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575599", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 211, "text": "Muscle pain is a frequent adverse effect of statins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33194498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Myopathy and rhabdomyolysis with lipid-lowering drugs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11869826", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "PURPOSE OF REVIEW: Lipid-lowering drugs are associated with myotoxicity, which ranges in severity from myalgias to rhabdomyolysis resulting in renal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17143099", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 350, "text": "Myopathy caused by HMG-CoA reductase inhibitors (statins) alone is rare, but occurs more frequently when a statin is used with gemfibrozil, a medication that likely has a direct toxic effect on muscles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12426921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Myotoxicity associated with lipid-lowering drugs.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17143099", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Rhabdomyolysis from the combination of a statin and gemfibrozil: an uncommon but serious adverse reaction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12426921", "endSection": "title" } ] }, { "body": "Which cytokine molecule activates SMADs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29973939", "http://www.ncbi.nlm.nih.gov/pubmed/15225217", "http://www.ncbi.nlm.nih.gov/pubmed/21975932", "http://www.ncbi.nlm.nih.gov/pubmed/16998902", "http://www.ncbi.nlm.nih.gov/pubmed/12957874", "http://www.ncbi.nlm.nih.gov/pubmed/23347175", "http://www.ncbi.nlm.nih.gov/pubmed/29558695", "http://www.ncbi.nlm.nih.gov/pubmed/17182123", "http://www.ncbi.nlm.nih.gov/pubmed/32235336", "http://www.ncbi.nlm.nih.gov/pubmed/19838011", "http://www.ncbi.nlm.nih.gov/pubmed/14500551", "http://www.ncbi.nlm.nih.gov/pubmed/30152848", "http://www.ncbi.nlm.nih.gov/pubmed/23727390", "http://www.ncbi.nlm.nih.gov/pubmed/20656683", "http://www.ncbi.nlm.nih.gov/pubmed/10974035", "http://www.ncbi.nlm.nih.gov/pubmed/15647278", "http://www.ncbi.nlm.nih.gov/pubmed/29892481", "http://www.ncbi.nlm.nih.gov/pubmed/29710466", "http://www.ncbi.nlm.nih.gov/pubmed/32334267", "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "http://www.ncbi.nlm.nih.gov/pubmed/10611754", "http://www.ncbi.nlm.nih.gov/pubmed/15184872", "http://www.ncbi.nlm.nih.gov/pubmed/12297674", "http://www.ncbi.nlm.nih.gov/pubmed/26956486", "http://www.ncbi.nlm.nih.gov/pubmed/19352540", "http://www.ncbi.nlm.nih.gov/pubmed/17513865", "http://www.ncbi.nlm.nih.gov/pubmed/20603212", "http://www.ncbi.nlm.nih.gov/pubmed/24129565", "http://www.ncbi.nlm.nih.gov/pubmed/19030025", "http://www.ncbi.nlm.nih.gov/pubmed/18322180", "http://www.ncbi.nlm.nih.gov/pubmed/15192102", "http://www.ncbi.nlm.nih.gov/pubmed/21095583" ], "ideal_answer": [ "SMADs are activated by Transforming growth factor beta (TGF beta)", "smads are activated by transforming growth factor-\u03b2 (tgf-\u03b2).", "SMADs are activated by Transforming growth factor beta (TGF-\u03b2)", "TGF-\u03b21 effects appear to be mediated through the canonical Smad pathway.", "SMADs are activated by Transforming growth factor beta (TGF beta).", "In an NEC animal model, oral administration of the isoform TGF-\u03b21 activated the downstream effector Smad2 in intestine and significantly reduced NEC incidence Transcription factor specificity protein 1 modulates TGF\u03b21/Smad signaling to negatively regulate SIGIRR expression by human M1 macrophages stimulated with substance P.", "The protein expression of TGF\u2011\u03b21/mothers against decapentaplegic homolog (Smad) and phosphoinositide 3\u2011kinase (PI3K)/protein kinase B (AKT) signaling pathways was evaluated by western blotting regulates the ERK/MAPK pathway independent of the SMAD pathway", "Activated SMADs are phosphorylated by TGF-\u03b2 superfamily type I receptors at two serine residues at an S-M/V-S motif at their extreme C-terminus. Once phosphorylated, activated R-SMADs form complexes with SMAD4, which accumulate in the nucleus where they activate or repress transcription." ], "exact_answer": [ "TGFbeta", "TGF\u03b2" ], "type": "factoid", "id": "5fe3131fa43ad3127800004a", "snippets": [ { "offsetInBeginSection": 421, "offsetInEndSection": 579, "text": "In an NEC animal model, oral administration of the isoform TGF-\u03b21 activated the downstream effector Smad2 in intestine and significantly reduced NEC incidence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129565", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 433, "text": "The TGF-\u03b2 signaling pathway outcome relies on the control of the spatial and temporal expression of >500 genes, which depend on the functions of the Smad protein along with those of diverse modulators of this signaling pathway, such as transcriptional factors and cofactors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29892481", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 967, "text": "he TGF-\u03b2/Smad pathway and coregulators Ski and SnoN clearly regulate each other through several positive and negative feedback mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29892481", "endSection": "abstract" }, { "offsetInBeginSection": 1413, "offsetInEndSection": 1517, "text": "These effects of PFD were mediated by the inhibition of the TGF\u2011\u03b21/Smad and PI3K/AKT signaling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30152848", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 994, "text": "The protein expression of TGF\u2011\u03b21/mothers against decapentaplegic homolog (Smad) and phosphoinositide 3\u2011kinase (PI3K)/protein kinase B (AKT) signaling pathways was evaluated by western blotting", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30152848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Transcription factor specificity protein 1 modulates TGF\u03b21/Smad signaling to negatively regulate SIGIRR expression by human M1 macrophages stimulated with substance P.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29558695", "endSection": "title" }, { "offsetInBeginSection": 1363, "offsetInEndSection": 1493, "text": "Importantly, this effect of Sp1 siRNA on TGF\u03b21 and SIGIRR was blunted by siRNA for Smad2, Smad3, or Smad4, but not by TAK-1 siRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29558695", "endSection": "abstract" }, { "offsetInBeginSection": 1943, "offsetInEndSection": 2065, "text": "Sp1 modulates TGF\u03b21/Smad signaling and negatively regulates SIGIRR protein production by macrophages after SP stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29558695", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "TGF-? regulates the ERK/MAPK pathway independent of the SMAD pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29710466", "endSection": "title" }, { "offsetInBeginSection": 488, "offsetInEndSection": 775, "text": "We found that EGFR-mediated ID3 expression was regulated by Smad5, which was directly phosphorylated by AKT. Furthermore, ID3 alone imparted GSC features to primary astrocytes derived from Ink4a/Arf-deficient mouse, and EGFR-ID3-IL-6 signaling axis gave rise to tumor cell heterogeneity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21975932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Oral administration of transforming growth factor-\u03b21 (TGF-\u03b21) protects the immature gut from injury via Smad protein-dependent suppression of epithelial nuclear factor \u03baB (NF-\u03baB) signaling and proinflammatory cytokine production.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129565", "endSection": "title" }, { "offsetInBeginSection": 1235, "offsetInEndSection": 1306, "text": "TGF-\u03b21 effects appear to be mediated through the canonical Smad pathway", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24129565", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 535, "text": "Numerous studies have shown that TGF-\u03b2 is the most important cytokine in the development of pulmonary fibrosis and plays a role through its downstream signaling molecule TGF-binding receptor Smads protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32334267", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 369, "text": "TGF-beta, a pleiotropic cytokine, regulates numerous genes involved in pancreatic carcinogenesis via activation of the Smads proteins and MUC4 promoter is rich in Smad-binding elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15184872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Cytokines of the transforming growth factor-beta (TGF-beta) superfamily transduce their signals by activating receptor-regulated Smads (R-Smads).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12297674", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1435, "text": "Altogether, these results indicate that upregulation of MUC4 by TGF-beta is restricted to well-differentiated pancreatic cancer cells, and point out a novel mechanism for TGF-beta as a key molecule in targeting MUC4 overexpression in pancreatic adenocarcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15184872", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 570, "text": "TGF\u03b2 signaling activates receptor SMADs, SMAD2 and SMAD3, which associate with a variety of nuclear factors to regulate gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20656683", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 368, "text": "We demonstrate that exogenous TGF-beta(1) can inhibit the expression of the proinflammatory adhesion molecule, E-selectin, in vascular endothelium exposed to inflammatory stimuli both in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10974035", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 297, "text": "Conversely, in conjunction with the inflammatory cytokine IL-6, TGF\u03b2 promotes Th17 cell differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20656683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "TGF\u03b2 is the quintessential cytokine of T cell homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20656683", "endSection": "abstract" }, { "offsetInBeginSection": 604, "offsetInEndSection": 750, "text": "Inhibitory Smads, including Smad6 and Smad7, are key regulators of TGF-beta/bone morphogenetic protein (BMP) signaling by negative feedback loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352540", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 965, "text": ", we have studied the immediate responses provoked by TGF-beta in major signaling pathways, and we have found that it induces a rapid activation of the SMAD pathway, i.e., phosphorylation and nuclear translocation of SMAD2, followed by dephosphorylation, most probably due to degradation by the proteasome. However, similar ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15225217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that induces growth arrest, tissue fibrosis, and epithelial-mesenchymal transition (EMT) through activation of Smad and non-Smad signaling pathways. EMT is ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19838011", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 431, "text": " well-understood classical TGF-beta signaling pathway, TGF-beta activates Smad signalling via its two cell surface receptors such as TbetaRII and ALK5/TbetaRI, leading to Smad-mediated transcriptional regulation. In additi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19352540", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 411, "text": "he role of transforming growth factor-beta (TGF-beta) as a key molecule in the development and progression of hepatic fibrosis via the activation of hepatic stellate cells, among other fibroblast populations, is without controversy. We her", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17513865", "endSection": "abstract" }, { "offsetInBeginSection": 1144, "offsetInEndSection": 1492, "text": "n, we show that: 1) TGF-beta receptor Type II is predominantly located on basolateral membrane and receptor stimulation activates Smad pathway; 2) TGF-beta1 down-regulates IL-6-induced tyrosine phoshorylation of STAT1 and STAT3 and ICAM-1 expression; and 3) Smad2 is required for the down-regulation of IL-6 signaling by TGF-beta. Collectively, our", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14500551", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 755, "text": " with an increase in TGF-beta in Alzheimer's disease, we found significant increases in phospho-Smad2, a major downstream signaling molecule of TGF-beta, in hippocampal neurons of Alzheimer's disease compared with age-matched control patients. However, in contra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16998902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "In the past three years, a novel signal transduction pathway downstream of the transforming growth factor-beta (TGF-beta) superfamily receptor serine-threonine kinases has been shown to be mediated by a family of latent transcription factors called 'Smads'. These", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10611754", "endSection": "abstract" }, { "offsetInBeginSection": 373, "offsetInEndSection": 629, "text": "monstrate that the antiinflammatory cytokine transforming growth factor-beta1 (TGF-beta1), which also permanently activates its canonical signalling pathway through SMAD proteins in BPH-1 cells, modifies the effects of IL-6 on cell proliferation. Important", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20603212", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 508, "text": "h transforming growth factor-beta (TGF-beta), the most potent fibrogenic cytokine for HSCs, which classically activates Smad signaling, and p38 MAPK signaling have been shown to influence collagen gene expression; however, the relative contribution and mechanisms that these two signaling pathways have in regulating collagen gene expression have not been investigated. The aim ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15647278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Design, synthesis and discovery of 2(1H)-quinolone derivatives for the treatment of pulmonary fibrosis through inhibition of TGF-\u03b2/smad dependent and independent pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32334267", "endSection": "title" }, { "offsetInBeginSection": 893, "offsetInEndSection": 1091, "text": "Further mechanism studies indicated that 20f reduced the expression of fibrogenic phenotypic protein \u03b1-SMA and collagen \u2160 by inhibiting the TGF-\u03b2/Smad dependent pathways and ERK1/2 and p38 pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32334267", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 892, "text": "Of these compounds, 20f was identified as the most active one and could inhibit TGF-\u03b2-induced collagen deposition of NRK-49F cells and mouse fibroblasts migration with comparable activity and lower cytotoxicity than nintedanib in\u00a0vitro.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32334267", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 709, "text": "One such a molecule is transforming growth factor-\u03b21 (TGF-\u03b21), a cytokine produced by many inflammatory and non-inflammatory cells and targeting virtually all the intestinal mucosal cell types, with the down-stream effect of activating intracellular Smad2/3 proteins and suppressing immune reactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973939", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 854, "text": "In patients with inflammatory bowel diseases (IBD), there is defective TGF-\u03b21/Smad signaling due to high Smad7, an inhibitor of TGF-\u03b21 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973939", "endSection": "abstract" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1434, "text": "We here review the role of TGF-\u03b21 and Smad7 in intestinal immunity, inflammation, and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973939", "endSection": "abstract" }, { "offsetInBeginSection": 855, "offsetInEndSection": 1040, "text": "Indeed, knockdown of Smad7 with a specific antisense oligonucleotide restores endogenous TGF-\u03b21 activity, thereby inhibiting inflammatory pathways in patients with IBD and colitic mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29973939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Transforming growth factor-\u03b21 (TGF-\u03b21) regulates cell junction restructuring via Smad-mediated repression and clathrin-mediated endocytosis of nectin-like molecule 2 (Necl-2).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "title" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1734, "text": "Taken together, TGF-\u03b21 is a potent cytokine that provides an effective mechanism in controlling Necl-2 expression in the testis via Smad-dependent gene repression and clathrin-mediated endocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1397, "text": "Mutational studies coupled with knockdown experiments have shown that TGF-\u03b21-induced Necl-2 repression requires activation of Smad proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1256, "text": "In addition, TGF-\u03b21 reduces Necl-2 mRNA via down-regulating Necl-2 promoter activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1536, "text": "EMSA and ChIP assays further confirmed that TGF-\u03b21 promotes the binding of Smad proteins onto MyoD and CCAATa motifs in vitro and in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 816, "text": "We have demonstrated that TGF-\u03b21 reduces Necl-2 mRNA and protein levels at both transcriptional and post-translational levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 817, "offsetInEndSection": 952, "text": "Using inhibitor and clathrin shRNA, we have revealed that TGF-\u03b21 induces Necl-2 protein degradation via clathrin-dependent endocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1063, "text": "Endocytosis assays further confirmed that TGF-\u03b21 accelerates the internalization of Necl-2 protein to cytosol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1170, "text": "Immunofluorescence staining also revealed that TGF-\u03b21 effectively removes Necl-2 from cell-cell interface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23741316", "endSection": "abstract" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1301, "text": "TGF-beta-mediated Smad transcriptional activity was severely inhibited in SOCS1-deficient cells in the presence of IFN-gamma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18322180", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1450, "text": "Such impairment of TGF-beta functions were not observed in SOCS3-overexpressed cells, indicating that suppression of Smads was independent of SOCS3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18322180", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 863, "text": "plus TGF-beta enhanced retinoic acid receptor-related orphan receptor (ROR)-gammat expression and suppressed IFN-gamma production in wild-type T cells, whereas these effects were severely impaired in SOCS1-deficient T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18322180", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Activins belong to the transforming growth factor (TGF)-\u03b2 family of multifunctional cytokines and signal via the activin receptors ALK4 or ALK7 to activate the SMAD2/3 pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32235336", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 275, "text": "TGFbeta binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19030025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Activins as Dual Specificity TGF-\u03b2 Family Molecules: SMAD-Activation via Activin- and BMP-Type 1 Receptors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32235336", "endSection": "title" }, { "offsetInBeginSection": 146, "offsetInEndSection": 264, "text": "Distinct R-Smads or combinations of R-Smads are activated by TGF-beta, activin, or bone morphogenetic proteins (BMPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12297674", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 209, "text": "TGF-\u03b2 signals through receptors to activate Smad proteins, which translocate into the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23727390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "TGF-beta (Transforming Growth Factor-beta) cytokines employ Smad proteins as the intracellular mediator of signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17182123", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 336, "text": "Canonical TGF-\u03b2 signaling results in the activation of Smad proteins, which are transcription factors that regulate target gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26956486", "endSection": "abstract" }, { "offsetInBeginSection": 963, "offsetInEndSection": 1286, "text": "Upon activation, the TGF-beta type I receptor phosphorylates Smad2 and Smad3, which then form complexes with Smad4 and accumulate in the nucleus to regulate transcription of a variety of genes that encode crucial determinants of cell fate, such as cell cycle components, differentiation factors and cell adhesion molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12957874", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 747, "text": "In endothelial cells, TGF-beta binds to two distinct type I receptor serine-threonine kinases, ALK-5 and ALK-1; the latter activates the same R-Smads that are activated by BMP and induces synthesis of Id (inhibitor of differentiation or inhibitor of DNA binding) proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12297674", "endSection": "abstract" }, { "offsetInBeginSection": 457, "offsetInEndSection": 698, "text": "To maintain intestinal integrity, the epithelial cells, myeloid cells and lymphocytes that inhabit the gut secrete TGF-\u03b2, which acts in both paracrine and autocrine fashions to activate its signal transducers, the SMAD transcription factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23347175", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 386, "text": "Activation of TGF-\u03b2 receptors leads to phosphorylation of Smad2 and Smad3, which oligomerize with Smad4 and accumulate in the nucleus where they recognize gene regulatory regions and orchestrate transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21095583", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 267, "text": "Upon TGF-beta stimulation, the cytoplasmic Smads become phosphorylated and consequently accumulate in the nucleus to regulate target gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17182123", "endSection": "abstract" }, { "offsetInBeginSection": 1640, "offsetInEndSection": 1897, "text": "In summary, our data show that S1P trans-activates the TGF-beta receptor and triggers activation of Smads followed by activation of connective tissue growth factor gene transcription and inhibition of IL-1beta-induced expression of iNOS, sPLA(2), and MMP-9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15192102", "endSection": "abstract" } ] }, { "body": "What is the Oncomine Dx Target test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30243889", "http://www.ncbi.nlm.nih.gov/pubmed/33185331" ], "ideal_answer": [ "The Oncomine Dx Target Test (ODxTT) is a next-generation sequencing-based companion diagnostic test, that could facilitate access to multiple biomarker testing using small tissue samples to support therapy decisions for patients with advanced NSCLC." ], "type": "summary", "id": "606bfca094d57fd879000072", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 230, "text": "The Oncomine Dx Target Test (ODxTT) is a next-generation sequencing-based companion diagnostic test which has been recently developed; however, its analysis success rate could be improved, especially for small samples.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33185331", "endSection": "abstract" }, { "offsetInBeginSection": 1652, "offsetInEndSection": 1877, "text": "Preliminary assessment of the investigational Oncomine Dx Target Test suggests it could facilitate access to multiple biomarker testing using small tissue samples to support therapy decisions for patients with advanced NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30243889", "endSection": "abstract" } ] }, { "body": "What are common variants at 12q14 and 12q24 associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22504421", "http://www.ncbi.nlm.nih.gov/pubmed/24361131" ], "ideal_answer": [ "Common variants at 12q14 and 12q24 are associated with hippocampal volume. Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors.", "Common variants at 12q14 and 12q24 are associated with hippocampal volume. As we age, our hippocampus (the part of the brain that is responsible for memory and cognition) becomes less and less efficient at storing information. As a result, the volume of the hippocampus shrinks.", "Common variants at 12q14 and 12q24 are associated with hippocampal volume.", "Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Common variants at 12q14 and 12q24 are associated with hippocampal volume." ], "exact_answer": [ "Hippocampal volume" ], "type": "factoid", "id": "60281eb11cb411341a0000f5", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Common variants at 12q14 and 12q24 are associated with hippocampal volume.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504421", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1271, "text": "Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 \u00d7 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 \u00d7 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 \u00d7 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 \u00d7 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 \u00d7 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504421", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Recently, two large genome-wide association studies (GWASs) have identified several variants at 12q14 and 12q24 which are associated with hippocampal volume, one of the most important biological markers of Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24361131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Recently, two large genome-wide association studies (GWASs) have identified several variants at 12q14 and 12q24 which are associated with hippocampal volume, one of the most important biological markers of Alzheimer's disease (AD). The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24361131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Common variants at 12q14 and 12q24 are associated with hippocampal volume", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504421", "endSection": "title" }, { "offsetInBeginSection": 485, "offsetInEndSection": 809, "text": "Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 \u00d7 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 \u00d7 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22504421", "endSection": "abstract" } ] }, { "body": "Which mutation is targeted by Sotorasib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "http://www.ncbi.nlm.nih.gov/pubmed/33097477", "http://www.ncbi.nlm.nih.gov/pubmed/33004338" ], "ideal_answer": [ "Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C." ], "exact_answer": [ "KRASG12C" ], "type": "factoid", "id": "601d74681cb411341a000042", "snippets": [ { "offsetInBeginSection": 139, "offsetInEndSection": 290, "text": "In a phase I trial, the KRASG12C inhibitor sotorasib elicited responses in about a third of patients with the disease and was generally well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33097477", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 426, "text": "Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.METHODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 1809, "offsetInEndSection": 1964, "text": "CONCLUSIONS: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 290, "text": "In a phase I trial, the KRASG12C inhibitor sotorasib elicited responses in about a third of patients with the disease and was generally well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33004338", "endSection": "abstract" }, { "offsetInBeginSection": 1815, "offsetInEndSection": 1969, "text": "SIONS: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grad", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 426, "text": "THODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 299, "text": " Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 412, "text": "Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.METHODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 404, "text": "er cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.METHODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" } ] }, { "body": "When is DELE1 exiting the mitochondrion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32132707", "http://www.ncbi.nlm.nih.gov/pubmed/32132706" ], "ideal_answer": [ "Mitochondrial stress stimulates OMA1-dependent cleavage of DELE1 and leads to the accumulation of DELE1 in the cytosol." ], "exact_answer": [ "Upon stress" ], "type": "factoid", "id": "603404f41cb411341a00014f", "snippets": [ { "offsetInBeginSection": 1025, "offsetInEndSection": 1201, "text": " stress-induced activation of OMA1 causes DELE1 to be cleaved into a short form that accumulates in the cytosol, where it binds to and activates HRI via its C-terminal portion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32132706", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 827, "text": "Mitochondrial stress stimulates OMA1-dependent cleavage of DELE1 and leads to the accumulation of DELE1 in the cytosol, where it interacts with HRI and activates the eIF2\u03b1 kinase activity of HRI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32132707", "endSection": "abstract" } ] }, { "body": "What is a ciliopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25398052", "http://www.ncbi.nlm.nih.gov/pubmed/27290837", "http://www.ncbi.nlm.nih.gov/pubmed/31147753", "http://www.ncbi.nlm.nih.gov/pubmed/30656919", "http://www.ncbi.nlm.nih.gov/pubmed/29334628", "http://www.ncbi.nlm.nih.gov/pubmed/21943201", "http://www.ncbi.nlm.nih.gov/pubmed/31965514", "http://www.ncbi.nlm.nih.gov/pubmed/28698599", "http://www.ncbi.nlm.nih.gov/pubmed/21816947", "http://www.ncbi.nlm.nih.gov/pubmed/30578505", "http://www.ncbi.nlm.nih.gov/pubmed/29650680", "http://www.ncbi.nlm.nih.gov/pubmed/31698098", "http://www.ncbi.nlm.nih.gov/pubmed/29534263", "http://www.ncbi.nlm.nih.gov/pubmed/21679365", "http://www.ncbi.nlm.nih.gov/pubmed/28625504", "http://www.ncbi.nlm.nih.gov/pubmed/20097287", "http://www.ncbi.nlm.nih.gov/pubmed/29281629", "http://www.ncbi.nlm.nih.gov/pubmed/29303074", "http://www.ncbi.nlm.nih.gov/pubmed/25388584", "http://www.ncbi.nlm.nih.gov/pubmed/22169048", "http://www.ncbi.nlm.nih.gov/pubmed/30867380", "http://www.ncbi.nlm.nih.gov/pubmed/26540106", "http://www.ncbi.nlm.nih.gov/pubmed/25599087" ], "ideal_answer": [ "A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function", "Ciliopathy is a rare disorder of the central nervous system characterized by defects in ciliary motility, endocytosis, and photoreceptors.", "ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking.", "Ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking." ], "type": "summary", "id": "601ffa7a1cb411341a000078", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking. Because nearly every cell in the body (including the photoreceptors) contains cilia, defects in ciliary proteins typically affect multiple organ systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30578505", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 460, "text": "Genetic defects affecting the structure or function of cilia can lead to a broad range of developmental and degenerative diseases known as ciliopathies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31698098", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 996, "text": "Ciliopathies can arise both as a result of genetic variants in spliceosomal proteins, or as a result of variants affecting splicing of specific cilia genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31698098", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 857, "text": "Dysregulation of the ciliary dynamics is linked with hereditary disorders, so called \"ciliopathy\", with clinical manifestations of microcephaly, polycystic kidney, situs inversus, polydactyly, and so on.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30867380", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 432, "text": "These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25599087", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "BACKGROUND: Meckel-Gruber syndrome is a ciliopathy, a lethal autosomal recessive disorder that occurs in all races and ethnicities; it is characterized by central nervous system abnormalities, resulting in mental retardation, bilateral renal cystic dysplasia and malformations of hands a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27290837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Loss of cilia and ciliary protein causes various abnormalities (called ciliopathy), including situs inversus, renal cystic diseases, polydactyly and dysgenesis of the nervous system. Renal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22169048", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 416, "text": "ver, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or function of cilia. To dete", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25398052", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 370, "text": "a ciliopathy, a spectrum of disorders whose causative genes encode proteins involved in the primary cilium apparatus. In order", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29334628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Mutations in genes encoding cilia proteins cause human ciliopathies, diverse disorders affecting many tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26540106", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 144, "text": "The dysfunction of cilia causes diseases known as ciliopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28698599", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Ciliopathy encompasses a diverse group of autosomal recessive genetic disorders caused by mutations in genes coding for components of the primary cilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31965514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "'Ciliopathies' are an emerging class of genetic multisystemic human disorders that are caused by a multitude of largely unrelated genes that affect ciliary structure/function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21943201", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 198, "text": "Ciliopathies are a class of inherited pleiotropic genetic disorders in which alterations in cilia assembly, maintenance, and/or function exhibit penetrance in the multiple organ systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29303074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The \"ciliopathies\" are a newly defined group of disorders characterized by defects in the structure or function of the cellular primary cilium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20097287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Ciliopathies are a group of hereditary disorders that result from structural or functional abnormalities of cilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31147753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Ciliopathies are a group of genetic diseases caused by defects in the function of cilia, that are cellular processes composed of a microtubule-based core.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30656919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29281629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Ciliopathies are disorders caused by ciliary dysfunction and can affect an organ system or tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29534263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Ciliopathies are life-threatening human diseases caused by defective cilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29650680", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 425, "text": "The ciliopathies are due to defects of the cellular antenna known as the primary cilium, a microtubule-based extension of cellular membranes found in nearly all cell types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Ciliopathies are a large group of human disorders caused by dysfunction of primary or motile cilia and unified by their overlapping clinical features (brain malformations, retinal dystrophy, cystic kidney disease, liver fibrosis and skeletal abnormalities).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25388584", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 781, "text": "Ciliopathies are unified by their overlapping clinical features and underlying mechanisms involving ciliary dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28625504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Ciliopathies are a genetically and phenotypically heterogeneous group of human developmental disorders whose root cause is the absence or dysfunction of primary cilia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21816947", "endSection": "abstract" } ] }, { "body": "Which histone mark is recognized by HP1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11242054", "http://www.ncbi.nlm.nih.gov/pubmed/27733730", "http://www.ncbi.nlm.nih.gov/pubmed/16222246", "http://www.ncbi.nlm.nih.gov/pubmed/19788305", "http://www.ncbi.nlm.nih.gov/pubmed/17406994", "http://www.ncbi.nlm.nih.gov/pubmed/11859155", "http://www.ncbi.nlm.nih.gov/pubmed/12897054", "http://www.ncbi.nlm.nih.gov/pubmed/17172865", "http://www.ncbi.nlm.nih.gov/pubmed/17542647", "http://www.ncbi.nlm.nih.gov/pubmed/19880879", "http://www.ncbi.nlm.nih.gov/pubmed/23166515", "http://www.ncbi.nlm.nih.gov/pubmed/11242053", "http://www.ncbi.nlm.nih.gov/pubmed/22514736", "http://www.ncbi.nlm.nih.gov/pubmed/18926834", "http://www.ncbi.nlm.nih.gov/pubmed/11882902", "http://www.ncbi.nlm.nih.gov/pubmed/22815475", "http://www.ncbi.nlm.nih.gov/pubmed/12068920" ], "ideal_answer": [ "h3k9me3 is the major histone mark that is recognized by hp1.", "Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.", "Histone H3 at lysine 9 trimethylation (H3K9me3)", "Histone H3 at lysine 9 (H3K9me3)", "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of heterochromatin in divergent animal species.", "HP1 can bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4. Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression.", "Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression.", "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins--a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure." ], "exact_answer": [ "H3K9me" ], "type": "factoid", "id": "5ebac76b0d431b5f7300000d", "snippets": [ { "offsetInBeginSection": 446, "offsetInEndSection": 552, "text": "Here we show that HP1 can bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11242054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11242053", "endSection": "title" }, { "offsetInBeginSection": 436, "offsetInEndSection": 715, "text": " Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins--a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11242053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of heterochromatin in divergent animal species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12068920", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 929, "text": "Finally, we provide evidence that Me9H3 is neither necessary nor sufficient for localisation of heterochromatin protein 1 (HP1) to chromosomal DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12068920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tai", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11859155", "endSection": "title" }, { "offsetInBeginSection": 110, "offsetInEndSection": 338, "text": "Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11859155", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 327, "text": "Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11882902", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 476, "text": " In Drosophila S2 cells, and on polytene chromosomes, methyl-Lys 27 and Pc are both excluded from areas that are enriched in methyl-Lys 9 and HP1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12897054", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 1032, "text": "To better understand the molecular basis for the selection of methyl-lysine binding sites, we solved the 1.8 A structure of the Pc chromodomain in complex with a H3 peptide bearing trimethyl-Lys 27, and compared it with our previously determined structure of the HP1 chromodomain in complex with a H3 peptide bearing trimethyl-Lys 9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12897054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Tri-methylation of histone H3 lysine 9 is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging and heterochromatin formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16222246", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 842, "text": "We investigated the role of Suz12 in constitutive heterochromatin and discovered that Suz12 is required for histone H3 lysine 9 tri-methylation (H3K9me3) in differentiated but not undifferentiated mouse embryonic stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17406994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Pericentric H3K9me3 Formation by HP1 Interaction-defective Histone Methyltransferase Suv39h1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27733730", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Pericentric regions form epigenetically organized, silent heterochromatin structures that accumulate histone H3 lysine 9 tri-methylation (H3K9me3) and heterochromatin protein 1 (HP1), a methylated H3K9-binding protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27733730", "endSection": "abstract" }, { "offsetInBeginSection": 1253, "offsetInEndSection": 1446, "text": "LSD1 cooperates with ASXL1 in transcriptional repression, presumably by removing H3K4 methylation, an active histone mark, but not H3K9 methylation, a repressive histone mark recognized by HP1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19880879", "endSection": "abstract" }, { "offsetInBeginSection": 850, "offsetInEndSection": 1135, "text": "We investigated the chromatin marks to which TFL2/LHP1 binds and show that, in vitro, TFL2/LHP1 binds to histone H3 di- or tri-methylated at lysine 9 (H3K9me2 or H3K9me3), the marks recognized by HP1, and to histone H3 trimethylated at lysine 27 (H3K27me3), the mark deposited by PRC2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17542647", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 611, "text": "Cbx3 is one of the paralogues of HP1 proteins, which has been reported to specifically recognize trimethylated histone H3K9 mark, and a consensus binding motif has been defined for the Cbx3 chromodomain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514736", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 689, "text": "For instance, tri-methylation of histone H3 lysine 9 (H3K9me3) is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging, and heterochromatin formation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17172865", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 596, "text": "Here we discuss functions of the Heterochromatin Protein 1 (HP1) family of proteins that recognize H3K9me, an epigenetic mark generated by the histone methyltransferases SU(VAR)3-9 and orthologues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18926834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Binding of heterochromatin protein 1 (HP1) to the histone H3 lysine 9 trimethylation (H3K9me3) mark is a hallmark of establishment and maintenance of heterochromatin. Al", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22815475", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 605, "text": "so on. Cbx3 is one of the paralogues of HP1 proteins, which has been reported to specifically recognize trimethylated histone H3K9 mark, and a consensus binding motif has been defined for the Cbx3 chromod", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22514736", "endSection": "abstract" }, { "offsetInBeginSection": 690, "offsetInEndSection": 830, "text": "Until now, little was known about the regulation of effector-histone mark interactions, and in particular, of the binding of HP1 to H3K9me3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17172865", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 1178, "text": "Recently, we and others presented evidence that a \"binary methylation-phosphorylation switch\" mechanism controls the dynamic release of HP1 from H3K9me3 during the cell cycle: phosphorylation of histone H3 serine 10 (H3S10ph) occurs at the onset of mitosis, interferes with HP1-H3K9me3 interaction, and therefore, ejects HP1 from its binding site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17172865", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1317, "text": "Our simulated results further confirm the essential role of cation-pi interactions for the binding of a methylated H3 tail by an HP1 chromodomain but indicate that the effect from an electrostatic origin is not dominant in distinguishing between the H3K9Me3 mark and its unmethylated counterpart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19788305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Heterochromatin protein 1 (HP1) proteins, recognized readers of the heterochromatin mark methylation of histone H3 lysine 9 (H3K9me), are important regulators of heterochromatin-mediated gene silencing and chromosome structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23166515", "endSection": "abstract" } ] }, { "body": "What is AZD8601?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30504800" ], "ideal_answer": [ "AZD8601 is a modified mRNA encoding vascular endothelial growth factor A (VEGF-A). Sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing." ], "type": "summary", "id": "602c192c1cb411341a000119", "snippets": [ { "offsetInBeginSection": 488, "offsetInEndSection": 662, "text": "Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30504800", "endSection": "abstract" }, { "offsetInBeginSection": 1154, "offsetInEndSection": 1410, "text": "Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30504800", "endSection": "abstract" } ] }, { "body": "List critical regions for 7p22.1 microduplication syndrome", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27866048" ], "ideal_answer": [ "7p22.1 microduplication syndrome is mainly characterized by developmental and speech delay, craniofacial dysmorphism and skeletal abnormalities. The minimal critical region includes two OMIM genes: ACTB and RNF216.", "7p22.1 microduplication syndrome is mainly characterized by developmental and speech delay, craniofacial dysmorphisms and skeletal abnormalities. The minimal critical region includes two OMIM genes: ACTB and RNF216." ], "exact_answer": [ [ "ACTB" ], [ "RNF216" ] ], "type": "list", "id": "603125341cb411341a00012b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 896, "text": "7p22.1 microduplication syndrome is mainly characterized by developmental and speech delay, craniofacial dysmorphisms and skeletal abnormalities. The minimal critical region includes two OMIM genes: ACTB and RNF216. Here, we report on a girl carrying the smallest 7p22.1 microduplication detected to date, contributing to the delineation of the clinical phenotype of the 7p22.1 duplication syndrome and to the refinement of the minimal critical region. Our patient shares several major features of the 7p22.1 duplication syndrome, including craniofacial dysmorphisms and speech and motor delay, but she also presents with renal anomalies. Based on present and published dup7p22.1 patients we suggest that renal abnormalities might be an additional feature of the 7p22.1 microduplication syndrome. We also pinpoint the ACTB gene as the key gene affecting the 7p22.1 duplication syndrome phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27866048", "endSection": "abstract" } ] }, { "body": "Which molecules are targeted by Trastuzumab Deruxtecan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32144719", "http://www.ncbi.nlm.nih.gov/pubmed/32005279", "http://www.ncbi.nlm.nih.gov/pubmed/31825192", "http://www.ncbi.nlm.nih.gov/pubmed/29037983", "http://www.ncbi.nlm.nih.gov/pubmed/31047804", "http://www.ncbi.nlm.nih.gov/pubmed/32058843", "http://www.ncbi.nlm.nih.gov/pubmed/31843763", "http://www.ncbi.nlm.nih.gov/pubmed/32469182", "http://www.ncbi.nlm.nih.gov/pubmed/33118153", "http://www.ncbi.nlm.nih.gov/pubmed/31087550", "http://www.ncbi.nlm.nih.gov/pubmed/32917537", "http://www.ncbi.nlm.nih.gov/pubmed/31574081", "http://www.ncbi.nlm.nih.gov/pubmed/31047803", "http://www.ncbi.nlm.nih.gov/pubmed/30351177", "http://www.ncbi.nlm.nih.gov/pubmed/29703841" ], "ideal_answer": [ "Trastuzumab deruxtecan is a HER2-directed antibody and DNA topoisomerase I inhibitor conjugate being developed for the treatment of HER2-expressing solid tumours, including breast cancer, gastric cancer, colorectal cancer and non-small cell lung cancer" ], "exact_answer": [ [ "HER2" ], [ "DNA topoisomerase I" ] ], "type": "list", "id": "6023598a1cb411341a00009b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The antibody-drug conjugate trastuzumab deruxtecan might become a promising new treatment option for patients with metastatic HER2-positive breast cancer whose disease has progressed after multiple therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31843763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31825192", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31825192", "endSection": "abstract" }, { "offsetInBeginSection": 2191, "offsetInEndSection": 2340, "text": "CONCLUSIONS: Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31825192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "BACKGROUND: There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32005279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "PURPOSE: Trastuzumab deruxtecan (T-DXd, formerly DS-8201a) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32058843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "Trastuzumab deruxtecan (ENHERTU\u00ae), a HER2-directed antibody and DNA topoisomerase I inhibitor conjugate, is being developed for the treatment of HER2-expressing solid tumours, including breast cancer, gastric cancer, colorectal cancer and non-small cell lung cancer by Daiichi Sankyo Company Ltd in collaboration with AstraZeneca.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32144719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "BACKGROUND: Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and topoisomerase I inhibitor payload.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31047804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND: Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and potent topoisomerase I inhibitor payload.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31047803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469182", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 437, "text": "[fam-] trastuzumab deruxtecan (DS-8201a) is a novel antibody-drug conjugate composed of the anti-HER2 antibody and the topoisomerase I inhibitor, an exatecan derivative.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31087550", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 476, "text": "Trastuzumab deruxtecan (also known as DS-8201) is an antibody-drug conjugate comprised of a humanised antibody against HER2, a novel enzyme-cleavable linker, and a topoisomerase I inhibitor payload.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29037983", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 223, "text": "Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "[Fam-] trastuzumab deruxtecan (DS-8201a) is a HER2 (ERBB2)-targeting antibody-drug conjugate, composed of a HER2-targeting antibody and a topoisomerase I inhibitor, exatecan derivative, that has antitumor effects in preclinical xenograft models and clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31574081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) conjugated to a topoisomerase I inhibitor (DXd) at a drug-to-antibody ratio (DAR) of 7-8.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30351177", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Trastuzumab deruxtecan (DS-8201) is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate with a novel enzyme-cleavable linker, a topoisomerase I inhibitor payload, and a drug-to-antibody ratio of \u2248 8.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33118153", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate with a topoisomerase I inhibitor exatecan derivative (DX-8951 derivative, DXd), has been reported to exert potent antitumor effects in xenograft mouse models and clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29703841", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 366, "text": "Trastuzumab deruxtecan (DS-8201a) is a next-generation antibody-drug conjugate composed of a monoclonal anti-HER2 antibody and a topoisomerase I inhibitor, an exatecan derivative (DX-8951f).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32917537", "endSection": "abstract" } ] }, { "body": "What is the function of the HSJ1 proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28031292", "http://www.ncbi.nlm.nih.gov/pubmed/21625540", "http://www.ncbi.nlm.nih.gov/pubmed/22522442", "http://www.ncbi.nlm.nih.gov/pubmed/25274842" ], "ideal_answer": [ "HSJ1 is a neuronal enriched member of the HSP40/DNAJ co-chaperone family." ], "exact_answer": [ "HSJ1 are chaperones." ], "type": "factoid", "id": "6081b64d4e6a4cf63000000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "HSJ1 (DNAJB2), a member of the DNAJ family of molecular chaperones, is a key player in neuronal proteostasis maintenance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28031292", "endSection": "abstract" }, { "offsetInBeginSection": 1200, "offsetInEndSection": 1450, "text": "HSJ1 is a neuronal enriched member of the HSP40/DNAJ co-chaperone family. Previous studies have shown that HSP40 proteins play a crucial role in protein aggregation and neurodegeneration in several neuronal types, in animal models and human diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "Homo sapiens J domain protein (HSJ1) is a J-domain containing co-chaperone that is known to stimulate ATPase activity of HSP70 chaperone, while it also harbors two ubiquitin (Ub)-interacting motifs (UIMs) that may bind with ubiquitinated substrates and potentially function in protein degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21625540", "endSection": "abstract" } ] }, { "body": "What is the indication for zolmitriptan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14642738", "http://www.ncbi.nlm.nih.gov/pubmed/9399013", "http://www.ncbi.nlm.nih.gov/pubmed/9399012", "http://www.ncbi.nlm.nih.gov/pubmed/9170337", "http://www.ncbi.nlm.nih.gov/pubmed/9399017", "http://www.ncbi.nlm.nih.gov/pubmed/14743270", "http://www.ncbi.nlm.nih.gov/pubmed/32752932", "http://www.ncbi.nlm.nih.gov/pubmed/11200789", "http://www.ncbi.nlm.nih.gov/pubmed/31889312", "http://www.ncbi.nlm.nih.gov/pubmed/9660035", "http://www.ncbi.nlm.nih.gov/pubmed/15992000", "http://www.ncbi.nlm.nih.gov/pubmed/9725543", "http://www.ncbi.nlm.nih.gov/pubmed/12083998", "http://www.ncbi.nlm.nih.gov/pubmed/31593739", "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "http://www.ncbi.nlm.nih.gov/pubmed/10640260", "http://www.ncbi.nlm.nih.gov/pubmed/16575626", "http://www.ncbi.nlm.nih.gov/pubmed/9071267", "http://www.ncbi.nlm.nih.gov/pubmed/11594437", "http://www.ncbi.nlm.nih.gov/pubmed/10210888", "http://www.ncbi.nlm.nih.gov/pubmed/18028032" ], "ideal_answer": [ "Development of a novel zolmitriptan intracutaneous microneedle system (Qtrypta\u2122) for the acute treatment of migraine", "Zolmitriptan is an effective medicine used in the treatment of migraine.", "zolmitriptan is approved for the treatment of migraine.", "zolmitriptan is approved for migraine treatment." ], "exact_answer": [ "migraine", "headache" ], "type": "factoid", "id": "601dbe2b1cb411341a00004d", "snippets": [ { "offsetInBeginSection": 1, "offsetInEndSection": 556, "text": "here are many new treatment options available for migraine and more are coming. Three calcitonin gene-related peptide (CGRP) antagonist monoclonal antibodies have been approved and a 4th is due in early 2020. Small molecule CGRP receptor-blocking oral compounds, both for acute care and prevention, are also coming. Four neurostimulators are available, with others on the way. New acute treatments coming soon include the 5HT1F agonist lasmiditan, a zolmitriptan intradermal micro-needle patch, and a nasal mist sumatriptan with a permeability enhancer. F", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31889312", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 156, "text": "Migraine has recently become a major interest to the neuroscientists. Zolmitriptan is an effective medicine used in the treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31593739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Development of a novel zolmitriptan intracutaneous microneedle system (Qtrypta\u2122) for the acute treatment of migraine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32752932", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Zolmitriptan is a novel and highly selective 5-HT(1B/1D) receptor agonist used as an acute oral treatment for migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14642738", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Zolmitriptan is a potent selective 5HT1B/1D receptor agonist for acute migraine therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9725543", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1235, "text": "SIONS: The 5 mg nasal formulation of zolmitriptan is a potential new option for the symptomatic treatment of cluster headache. This ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Zolmitriptan (Zomig, formerly 311C90) is a novel, oral, acute treatment for migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9399013", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Zolmitriptan (Zomig, formerly 311C90) is a selective 5-hydroxytryptamine (5-HT)1B/1D-receptor agonist with central and peripheral activity for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9660035", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 156, "text": "Zolmitriptan is an effective medicine used in the treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31593739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "RATIONALE: Zolmitriptan is an anti-migraine agent with action at 5-HT1B/D receptors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11594437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "311C90 (Zomig; zolmitriptan) is a novel, selective serotonin (5HT)1B/1D receptor agonist with both central and peripheral activity, now in late-stage clinical development for acute oral treatment of migraine. Sever", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9071267", "endSection": "abstract" }, { "offsetInBeginSection": 1829, "offsetInEndSection": 1987, "text": "ion and with a tendency to recur (e.g. menstrual headaches) either naratriptan or zolmitriptan would be appropriate. Naratriptan has lower reported adverse ev", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11200789", "endSection": "abstract" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1283, "text": "either rizatriptan or zolmitriptan would be appropriate for moderate and severe headache. Rizatriptan has a more rapid on", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11200789", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 465, "text": "he serotonin (5HT1B/D) agonist zolmitriptan (311C90) has been shown to be effective in the treatment of acute attacks of migraine and experimental data suggest that it may have both peripheral and central sites of action. This s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9170337", "endSection": "abstract" }, { "offsetInBeginSection": 1504, "offsetInEndSection": 1615, "text": "Naratriptan would appear to have a lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11200789", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1131, "text": "Critical differences for the new TELs (naratriptan, rizatriptan and zolmitriptan) which may lead to more rational migraine management: Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5.0 mg) have demonstrated superior efficacy to sumatriptan 100 mg, and 25 and 50 mg respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11200789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have been approved for marketing in most countries of the world (naratriptan, rizatriptan and zolmitriptan).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11200789", "endSection": "abstract" }, { "offsetInBeginSection": 1868, "offsetInEndSection": 1945, "text": "menstrual headaches) either naratriptan or zolmitriptan would be appropriate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11200789", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 832, "text": " Zolmitriptan is effective in the treatment of migraine associated with menses and migraine with aura", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Zolmitriptan: a review of its use in migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "title" }, { "offsetInBeginSection": 1500, "offsetInEndSection": 1714, "text": " For relief of migraine headache, zolmitriptan 5mg had similar efficacy to sumatriptan 100mg for a single attack, but generally was more effective than sumatriptan 25 and 50mg for multiple attacks, in single trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 2213, "offsetInEndSection": 2370, "text": "NCLUSION: Zolmitriptan is effective across a wide range of migraine subtypes, maintains efficacy when used in the long term and is generally well tolerated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1499, "text": " Zolmitriptan has also demonstrated efficacy in the treatment of persistent and/or recurrent migraine headache", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 966, "text": " There is some evidence to support the use of zolmitriptan in patients with migraine who have had a poor response to previous therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1205, "text": " The efficacy of zolmitriptan appears to be maintained, with no tachyphylaxis, following repeated administration for multiple attacks of migraine over a prolonged period of time, with high headache response rates reported over all attacks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1388, "text": " In comparison with placebo, the incidence of persistent migraine headache is reduced by zolmitriptan and recurrent migraine headache occurs less frequently with the active treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "[Experience with intranasal zolmitriptan in cluster headache].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575626", "endSection": "title" }, { "offsetInBeginSection": 1113, "offsetInEndSection": 1232, "text": " 5 mg nasal formulation of zolmitriptan is a potential new option for the symptomatic treatment of cluster headache. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575626", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 191, "text": "The objective is to analyse our experience with the new intranasal formulation of zolmitriptan 5 mg in the symptomatic treatment of cluster headache in daily clinical practice.P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16575626", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 530, "text": "Zolmitriptan is FDA approved for the treatment of acute migraine attacks and there is recent literature demonstrating its efficacy in the acute treatment of cluster attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18028032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Zolmitriptan (Zomig; formerly 311C90) is a novel 5-hydroxytryptamine (5HT)1B/1D receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9399012", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1273, "text": "Zolmitriptan is a suitable first-line drug for acute treatment for migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15992000", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Zolmitriptan, a selective 5-HT(1B/D) agonist was developed for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14743270", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 821, "text": "lmitriptan. Zolmitriptan is effective in the treatment of migraine associated with menses and migrain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10473025", "endSection": "abstract" }, { "offsetInBeginSection": 1011, "offsetInEndSection": 1112, "text": "Zolmitriptan is effective in the treatment of migraine associated with menses and migraine with aura.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12083998", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 356, "text": "Zolmitriptan, a 5-hydroxytryptophan(1B/1D) receptor agonist, is once such drug that is used in acute migraine therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18028032", "endSection": "abstract" }, { "offsetInBeginSection": 1380, "offsetInEndSection": 1483, "text": "Zolmitriptan has also shown efficacy in the treatment of persistent and/or recurrent migraine headache.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12083998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Zolmitriptan is effective for the treatment of persistent and recurrent migraine headache.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10640260", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Zolmitriptan is a selective 5-HT1B/1D receptor agonist for acute oral migraine therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10210888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Zolmitriptan is a 5-HT1B/1D receptor agonist for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10640260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Zolmitriptan (Zomig, formerly 311C90) is a novel, oral antimigraine drug that is consistently effective and well tolerated in the acute treatment of migraine headache and its associated symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9399017", "endSection": "abstract" } ] }, { "body": "What percentage of C. elegans genes reside in operons?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "http://www.ncbi.nlm.nih.gov/pubmed/16752214", "http://www.ncbi.nlm.nih.gov/pubmed/27631780", "http://www.ncbi.nlm.nih.gov/pubmed/12386927", "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "http://www.ncbi.nlm.nih.gov/pubmed/25936768", "http://www.ncbi.nlm.nih.gov/pubmed/19204375", "http://www.ncbi.nlm.nih.gov/pubmed/18218978", "http://www.ncbi.nlm.nih.gov/pubmed/21177958" ], "ideal_answer": [ "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes.", "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter.", "Approximately 15% of the genes in C. elegans are operons.", "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Both methods indicate that the pre-mRNAs of about 70% of Caenorhabditis elegans genes are trans-spliced and as many as a quarter are transcribed in these operons.", "about 15% of genes in Caenorhabditis elegans, a model organism belonging to Nematoda, reside in operons (Blumenthal et al. 2002; Blumenthal and Gleason 2003). For two reasons, nematode and prokaryotic operons are believed to have separate origins.", "Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter.", "Our data indicate that 15% of the genes in C. elegans reside in operons.", "Approximately 15% of the genes in C. elegans are located in operons, of which at least 15% are known to date.", "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome.", "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome.", "Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome.", "Approximately 15% of the genes in C. elegans are located in operons.", "About 15% of all C. elegans genes reside in operons. URL_0 > Nearly 15 percent of the ~20,000 C. Elegans genes are contained in operon, multigene clusters controlled by a single promoter.", "Evidence indicates that the genome of C. elegans contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes." ], "exact_answer": [ "15%" ], "type": "factoid", "id": "5fe09c99a43ad31278000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25936768", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1198, "text": "Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 495, "text": "Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16752214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18218978", "endSection": "abstract" }, { "offsetInBeginSection": 1258, "offsetInEndSection": 1337, "text": "Overall, our data demonstrate that >17% of all C. elegans genes are in operons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21177958", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1197, "text": "Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12075352", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1182, "text": "Like more than 15% of C. elegans genes, xrn-2 occurs in an operon, and we identify additional operons under its control, consistent with a broader function of XRN2 in polycistronic gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27631780", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 166, "text": "provides convincing evidence that at least 15% of Caenorhabditis elegans genes are co-transcribed within over a thousand operons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12386927", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 218, "text": "In the nematode Caenorhabditis elegans, the genome contains >1000 operons that compose approximately 15% of the protein-coding genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19204375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Genes in nematode and ascidian genomes frequently occur in operons--multiple genes sharing a common promoter to generate a polycistronic primary transcript--and such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20382830", "endSection": "abstract" } ] }, { "body": "What is the most advanced phase of clinical trial that fingolimod has entered?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29938336" ], "ideal_answer": [ "Fingolimod has been assessed in phase IV clinical trials." ], "exact_answer": [ "phase IV" ], "type": "factoid", "id": "60527e8c94d57fd879000012", "snippets": [ { "offsetInBeginSection": 246, "offsetInEndSection": 437, "text": "In this longitudinal, 2-year prospective, phase IV, single-blind study, 40 MS patients treated with fingolimod and 39 untreated age, gender, and disability-matched MS patients were enrolled. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29938336", "endSection": "abstract" } ] }, { "body": "What is caused by a gain-of-function mutation in CLCN2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29403011", "http://www.ncbi.nlm.nih.gov/pubmed/29403012" ], "ideal_answer": [ "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism, which is the most common and curable form of arterial hypertension.", "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. ", "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. The leukodystrophy of Glialcam, which is encoded in the gene, is associated with dysregulated extracellular ion homeostasis, and abnormal RPE cell function.", "Primary aldosteronism is a rare autosomal dominant disorder caused by gain-of-function mutations in CLCN2 and clinically characterized by severe intrauterine and post-natal growth retardation", "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism.", "Primary aldosteronism is an autosomal dominant disorder caused by gain-of-function mutations in CLCN2.", "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Primary aldosteronism is the most common and curable form of secondary arterial hypertension.", "Primary aldosteronism is the most common and curable form of secondary arterial hypertension. A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism." ], "exact_answer": [ "Primary aldosteronism" ], "type": "factoid", "id": "605fb41094d57fd879000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403012", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 361, "text": "Primary aldosteronism is the most common and curable form of secondary arterial hypertension. We performed whole-exome sequencing in patients with early-onset primary aldosteronism and identified a de novo heterozygous c.71G>A/p.Gly24Asp mutation in the CLCN2 gene, encoding the voltage-gated ClC-2 chloride channel 1 , in a patient diagnosed at 9 years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403012", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 620, "text": "ts in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride chan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403012", "endSection": "title" }, { "offsetInBeginSection": 290, "offsetInEndSection": 574, "text": ". Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proban", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403011", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 361, "text": "We performed whole-exome sequencing in patients with early-onset primary aldosteronism and identified a de novo heterozygous c.71G>A/p.Gly24Asp mutation in the CLCN2 gene, encoding the voltage-gated ClC-2 chloride channel 1 , in a patient diagnosed at 9 years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403012", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 907, "text": "Our data indicate that CLCN2 mutations cause primary aldosteronism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29403012", "endSection": "abstract" } ] }, { "body": "Which treatments were compared in the UNBLOCS trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32558178", "http://www.ncbi.nlm.nih.gov/pubmed/32901611", "http://www.ncbi.nlm.nih.gov/pubmed/28412960", "http://www.ncbi.nlm.nih.gov/pubmed/32622397" ], "ideal_answer": [ "The UNBLOCS trial compared thulium laser transurethral vaporesection of the prostate versus transurethral resection of the prostate for men with lower urinary tract symptoms or urinary retention." ], "exact_answer": [ [ "thulium laser transurethral vaporesection of the prostate" ], [ "transurethral resection of the prostate" ] ], "type": "list", "id": "6027505c1cb411341a0000e6", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Thulium laser transurethral vaporesection of the prostate versus transurethral resection of the prostate for men with lower urinary tract symptoms or urinary retention (UNBLOCS): a randomised controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32622397", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 736, "text": "BACKGROUND: Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction. Thulium laser transurethral vaporesection of the prostate (ThuVARP) is a technique with suggested advantages over TURP, including reduced complications and hospital stay. We aimed to investigate TURP versus ThuVARP in men with lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction.METHODS: In this randomised, blinded, parallel-group, pragmatic equivalence trial, men in seven UK hospitals with bothersome lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction were randomly assigned (1:1) at the point of surgery to receive ThuVARP or TURP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32622397", "endSection": "abstract" }, { "offsetInBeginSection": 1845, "offsetInEndSection": 1988, "text": "INTERPRETATION: TURP and ThuVARP were equivalent for urinary symptom improvement (IPSS) 12-months post-surgery, and TURP was superior for Qmax.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32622397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The cost-effectiveness of transurethral resection of the prostate vs thulium laser transurethral vaporesection of the prostate in the UNBLOCS randomised controlled trial for benign prostatic obstruction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32558178", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "OBJECTIVE: To determine the cost-effectiveness of the current 'gold standard' operation of transurethral resection of the prostate (TURP) compared to the new laser technique of thulium laser transurethral vaporesection of the prostate (ThuVARP) in men with benign prostatic obstruction (BPO) within the UK National Health Service (NHS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32558178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Thulium laser transurethral vaporesection versus transurethral resection of the prostate for benign prostatic obstruction: the UNBLOCS RCT.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32901611", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "A randomised controlled trial to determine the clinical and cost effectiveness of thulium laser transurethral vaporesection of the prostate (ThuVARP) versus transurethral resection of the prostate (TURP) in the National Health Service (NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28412960", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "The cost-effectiveness of transurethral resection of the prostate vs thulium laser transurethral vaporesection of the prostate in the UNBLOCS randomised controlled trial for benign prostatic obstruction", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32558178", "endSection": "title" } ] }, { "body": "Which are the ligands of the Roundabout (Robo) receptors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30700556", "http://www.ncbi.nlm.nih.gov/pubmed/29217730", "http://www.ncbi.nlm.nih.gov/pubmed/31939155", "http://www.ncbi.nlm.nih.gov/pubmed/30820596" ], "ideal_answer": [ "Roundabouts comprise a family of single-pass transmembrane receptors facilitating this process upon interaction with the soluble extracellular ligand Slit protein family emanating from the midline." ], "exact_answer": [ [ "SLIT" ], [ "NELL", "neural EGFL-like" ] ], "type": "list", "id": "603557ef1cb411341a000155", "snippets": [ { "offsetInBeginSection": 44, "offsetInEndSection": 105, "text": "Slit ligands and their Roundabout (Robo) family of receptors ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30700556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30700556", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 72, "text": "SLIT-ROBO is a ligand-receptor family of neuronal guidance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30820596", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 342, "text": "Roundabouts comprise a family of single-pass transmembrane receptors facilitating this process upon interaction with the soluble extracellular ligand Slit protein family emanating from the midline. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31939155", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "The repellant ligand Slit and its Roundabout (Robo) family receptors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29217730", "endSection": "abstract" } ] }, { "body": "What is the function of kisspeptin in the brain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27246282", "http://www.ncbi.nlm.nih.gov/pubmed/18840491", "http://www.ncbi.nlm.nih.gov/pubmed/23549999", "http://www.ncbi.nlm.nih.gov/pubmed/32926943", "http://www.ncbi.nlm.nih.gov/pubmed/20670626", "http://www.ncbi.nlm.nih.gov/pubmed/20064520", "http://www.ncbi.nlm.nih.gov/pubmed/23348107", "http://www.ncbi.nlm.nih.gov/pubmed/29867758", "http://www.ncbi.nlm.nih.gov/pubmed/31812674", "http://www.ncbi.nlm.nih.gov/pubmed/31790683", "http://www.ncbi.nlm.nih.gov/pubmed/27349533", "http://www.ncbi.nlm.nih.gov/pubmed/30333302", "http://www.ncbi.nlm.nih.gov/pubmed/22649563", "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "http://www.ncbi.nlm.nih.gov/pubmed/19210293", "http://www.ncbi.nlm.nih.gov/pubmed/23638144", "http://www.ncbi.nlm.nih.gov/pubmed/20738704", "http://www.ncbi.nlm.nih.gov/pubmed/31729619" ], "ideal_answer": [ "Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis. It is the most potent factor known to induce GnRH release. Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus", " Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis", "The function of kisspeptin in the brain is not really known, but it plays an integral role in the regulation of hunger, sex, and reproduction. Kisspeptin is the most potent factor known to induce GnRH release in Mice. URL_0", " Kisspeptin is the most potent factor known to induce GnRH release. Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus", "Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis. Kisspeptin also preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain.", "kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus and human neuronal cell line.", " Kisspeptin is the most potent factor known to induce GnRH release. Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis Intraperitoneal Treatment of Kisspeptin Suppresses Appetite and Energy Expenditure and Alters Gastrointestinal Hormones in Mice.", "Kisspeptin is a leptin-like protein that exerts important effects on the regulation of food intake and energy expenditure by interacting with the glucocorticoid receptor in the brain.", "Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis." ], "type": "summary", "id": "604d41ba94d57fd879000005", "snippets": [ { "offsetInBeginSection": 342, "offsetInEndSection": 410, "text": " Kisspeptin is the most potent factor known to induce GnRH release. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31790683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32926943", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 183, "text": " Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31729619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Intraperitoneal Treatment of Kisspeptin Suppresses Appetite and Energy Expenditure and Alters Gastrointestinal Hormones in Mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31729619", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "The kisspeptin system, a known regulator of reproduction in fish,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31812674", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 541, "text": "The action of kisspeptin in the regulation of gonadal function has been widely studied, but little is known as concerns its function in limbic brain structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23348107", "endSection": "abstract" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1696, "text": "Kisspeptin signaling may also serve diverse functions outside of the classical realm of reproductive neuroendocrinology, including the regulation of metastasis in certain cancers, vascular dynamics, placental physiology, and perhaps even higher-order brain function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1429, "text": "Kisspeptin signaling in the brain has been implicated in mediating the negative feedback action of sex steroids on gonadotropin secretion, generating the preovulatory GnRH/LH surge, triggering and guiding the tempo of sexual maturation at puberty, controlling seasonal reproduction, and restraining reproductive activity during lactation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1592, "text": "SION: Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30333302", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1469, "text": "Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22649563", "endSection": "abstract" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1328, "text": "is wide consensus that kisspeptin signaling in the brain is essential, providing the impetus to GnRH neurons to awaken at puberty and reigning the activity of these neurons when discretion is advised. We celebrate th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23549999", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 500, "text": "he present study aimed to identify kisspeptin neurons in the bovine hypothalamus, clarifying that a central mechanism is also present in the cattle brain, as kisspeptin is known to play an important role in the stimulation of gonadotropin-releasing hormone (GnRH)/gonadotropin secretion in other mammals. To ch", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27349533", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 606, "text": "ide here a review of kisspeptin actions on neuronal populations throughout the brain including the magnocellular oxytocin and vasopressin neurons, and cells within the arcuate nucleus, hippocampus, and amygdala. The actions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27246282", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 404, "text": "lations of kisspeptin neurones in the brain may control two modes of GnRH release to time the onset of puberty and regulate oestrous cyclicity in rats and mice. One popu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19210293", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 378, "text": "owever, in spite of wide kisspeptin receptor distribution in the brain, especially in the preoptic area and hypothalamus, the research focus has mostly been confined to the kisspeptin regulation on GnRH neurons. Here,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23638144", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 347, "text": "The kisspeptins activate the G-protein coupled receptor GPR54 and are strongly implicated in puberty onset and in regulation of the hypothalamo-pituitary gonadal axis in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18840491", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1446, "text": "In addition, kisspeptin nerve terminals and receptors are found in other hypothalamic area suggesting that kisspeptins are involved in regulation of other yet unknown homeostatic or neuroendocrine functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18840491", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 640, "text": "Kisspeptin neurons directly innervate and stimulate GnRH neurons, which are the final common pathway through which the brain regulates reproduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1090, "text": "Kisspeptin neurons express the estrogen receptor and the androgen receptor, and these cells are direct targets for the action of gonadal steroids in both male and female animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 911, "text": "Kisspeptin neurons are sexually differentiated with respect to cell number and transcriptional activity in certain brain nuclei, and some kisspeptin neurons express other cotransmitters, including dynorphin and neurokinin B (whose physiological significance is unknown).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Kisspeptin (a product of the Kiss1 gene) and its receptor (GPR54 or Kiss1r) have emerged as key players in the regulation of reproduction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 272, "text": "Mutations in humans or genetically targeted deletions in mice of either Kiss1 or Kiss1r cause profound hypogonadotropic hypogonadism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19770291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "The kiss1 gene product kisspeptin is now considered to be an essential regulator of the hypothalamic-pituitary-gonadal (HPG) axis in most vertebrate species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20738704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus and human neuronal cell line.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32926943", "endSection": "title" }, { "offsetInBeginSection": 200, "offsetInEndSection": 450, "text": "In the brain, Kiss1 gene is mainly expressed in the hypothalamic region, but KissR gene is widely distributed throughout the brain, suggesting that kisspeptin-KissR system may be involved in not only reproductive, but also non-reproductive functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29867758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Kisspeptins are a family of neuropeptides encoded by Kiss1 and Kiss2 genes, and participate in neuroendocrine regulation of gonadotropin-releasing hormone (GnRH) secretion through activating their receptor, Kiss1r (or GPR54).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20670626", "endSection": "abstract" }, { "offsetInBeginSection": 1849, "offsetInEndSection": 2167, "text": "The results demonstrated that the action of kisspeptin-13 on the facilitation of passive avoidance learning and memory consolidation is mediated, at least in part, through interactions of the \u03b12-adrenergic, beta-adrenergic, 5-HT2 serotonergic, muscarinic cholinergic and GABA-A-ergic receptor systems and nitric oxide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23348107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Kisspeptin is a potent regulator of the hypothalamo-pituitary-gonadal axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20064520", "endSection": "abstract" } ] }, { "body": "Is Nanog repressed in pluripotent stem cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20824089", "http://www.ncbi.nlm.nih.gov/pubmed/19036726", "http://www.ncbi.nlm.nih.gov/pubmed/17267691", "http://www.ncbi.nlm.nih.gov/pubmed/18223644", "http://www.ncbi.nlm.nih.gov/pubmed/16908534", "http://www.ncbi.nlm.nih.gov/pubmed/18454139", "http://www.ncbi.nlm.nih.gov/pubmed/20026622", "http://www.ncbi.nlm.nih.gov/pubmed/16790525", "http://www.ncbi.nlm.nih.gov/pubmed/25544848", "http://www.ncbi.nlm.nih.gov/pubmed/15939376", "http://www.ncbi.nlm.nih.gov/pubmed/24489122", "http://www.ncbi.nlm.nih.gov/pubmed/26296469", "http://www.ncbi.nlm.nih.gov/pubmed/19845468", "http://www.ncbi.nlm.nih.gov/pubmed/15494369", "http://www.ncbi.nlm.nih.gov/pubmed/22713603", "http://www.ncbi.nlm.nih.gov/pubmed/21304588" ], "ideal_answer": [ "The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm.", "No. The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm.", "Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm." ], "exact_answer": "no", "type": "yesno", "id": "5fdb415ba43ad31278000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15494369", "endSection": "title" }, { "offsetInBeginSection": 685, "offsetInEndSection": 844, "text": "Interestingly, cell aggregation by itself induced Nanog repression at the outer layer, which was essential for aggregation-induced primitive endoderm formation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15494369", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 996, "text": "early embryonic development, when downregulation of Nanog plays a crucial role.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15494369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16908534", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1449, "text": "These data indicate that the Grb2/Mek pathway primarily mediates Nanog gene repression upon ES cell differentiation into primitive endoderm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16908534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454139", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Nanog and Oct4 are essential transcription factors that regulate self-renewal and pluripotency of ES cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454139", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 194, "text": "the mechanisms by which Nanog and Oct4 modulate ES cell fate remain unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454139", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 678, "text": "Nanog, Oct4 and repressor proteins co-occupy Nanog-target genes in mouse ES cells, suggesting that Nanog and Oct4 together may communicate with distinct repression complexes to control gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454139", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1467, "text": "Nanog and Oct4 associate with unique repressor complexes on their target genes to control ES cell fate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18454139", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1303, "text": "he main finding of this study is that knockdown of Trp53 and Pten independently resulted in significantly higher expression levels of the pluripotency-associated gene Nanog, and we hypothesize that TRP53 and PTEN mediated repression is important for the insulation of male germ cells from pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19845468", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 342, "text": "The homeodomain transcription factor NANOG plays a central role in maintaining hESC pluripotency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20824089", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1303, "text": "The newly derived NANOG reporter hESC lines present novel tools to visualize NANOG expression in viable hESCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20824089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Loss of Pten causes tumor initiation following differentiation of murine pluripotent stem cells due to failed repression of Nanog.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21304588", "endSection": "title" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1124, "text": "Furthermore, our data show that the mechanism by which Pten null ECCs emerge in vitro and cause tumors in vivo is through increased survival and self-renewal, due to failed repression of the transcription factor Nanog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21304588", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 237, "text": "We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC) lines following exposure to the differentiating agent DETA/NO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25544848", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 895, "text": "Furthermore, Nanog binding to the promoter of Brachyury leads to repression of this gene, thus disrupting mesendoderm transition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25544848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Maintaining pluripotency and indefinite self-renewal of embryonic stem cells requires a tight control of the expression of several key stemness factors, particularly Nanog and Oct4 transcription factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24489122", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 304, "text": "Current evidence suggests that ES cells maintain their pluripotent state by expressing a battery of transcription factors including Oct4 and Nanog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16790525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Embryonic stem (ES) cell pluripotency is dependent upon sustained expression of the key transcriptional regulators Oct4, Nanog, and Sox2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17267691", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 980, "text": "The expression of Oct4 is activated by FoxD3 and Nanog but repressed by Oct4 itself, thus, exerting an important negative feedback loop to limit its own activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16790525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Nanog, Oct4, and Sox2 form the core of a transcription factor network that maintains embryonic stem cells in the pluripotent state in both humans and mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19036726", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 602, "text": "w that Bmi1 is enriched in the extraembryonic (endoderm [XEN] and trophectodermal stem [TS]) compartment and repressed by Nanog in pluripotent embryonic stem (ES) cells. In vivo, Bm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Nanog is a newly identified transcriptional factor bearing a homeodomain and expressed in pluripotential cells of preimplantation and early postimplantation embryos, and embryonic stem (ES) and embryonic germ (EG) cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15939376", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 334, "text": "Knockout experiments indicate that Nanog functions as a key player in maintaining the pluripotency of stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15939376", "endSection": "abstract" }, { "offsetInBeginSection": 1444, "offsetInEndSection": 1570, "text": "Thus, in germ cell development, NANOG is expressed in proliferating germ cells, in which nuclear reprogramming is progressing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15939376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NFkappaB and cooperating with Stat3.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18223644", "endSection": "title" }, { "offsetInBeginSection": 430, "offsetInEndSection": 640, "text": "We performed a genome-wide screen that combined full-length mESC transcriptome genomic mapping data with chromatin immunoprecipitation genomic location maps of the key mESC transcription factors Oct4 and Nanog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20026622", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26296469", "endSection": "abstract" }, { "offsetInBeginSection": 831, "offsetInEndSection": 1012, "text": "Notably, the expression of Nanog, a key pluripotency regulator and repressor of extraembryonic endoderm specification in ES cells, was significantly reduced in Zic3 knockdown cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17267691", "endSection": "abstract" } ] }, { "body": "What is the mode of administration of Ubrogepant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31537107", "http://www.ncbi.nlm.nih.gov/pubmed/31899602", "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "http://www.ncbi.nlm.nih.gov/pubmed/29136283", "http://www.ncbi.nlm.nih.gov/pubmed/32020557" ], "ideal_answer": [ "Ubrogepant (MK-1602) is administered orally." ], "exact_answer": [ "oral" ], "type": "factoid", "id": "6026d8bf1cb411341a0000ce", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 387, "text": "We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29136283", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 150, "text": "Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for the acute treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31537107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Ubrogepant (Ubrelvy\u2122) is an orally administered, small molecule, highly-selective, calcitonin gene-related peptide (CGRP) antagonist that was developed by Allergan under license to Merck & Co. as an acute treatment for migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32020557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist intended for the acute treatment of migraine attacks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31899602", "endSection": "abstract" } ] }, { "body": "Are synonymous sites in primates and rodents functionally constrained?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26563252" ], "ideal_answer": [ "No. Synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. In primates up to 24% of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally." ], "exact_answer": "no", "type": "yesno", "id": "6060e03394d57fd879000048", "snippets": [ { "offsetInBeginSection": 397, "offsetInEndSection": 1103, "text": "To resolve this contradiction between expectations and observations, we used processed pseudogenes as a model for strict neutral evolution, and estimated selective constraint on synonymous sites using the rate of substitution at pseudosynonymous and pseudononsynonymous sites in pseudogenes as the neutral expectation. After controlling for the effects of GC content, our results were similar to those from previous studies, i.e., synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. Specifically, our results indicated that in primates up to 24% of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26563252", "endSection": "abstract" } ] }, { "body": "Which animal bite can cause Capnocytophaga canimorsus infection?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20407357", "http://www.ncbi.nlm.nih.gov/pubmed/25828064", "http://www.ncbi.nlm.nih.gov/pubmed/30706413", "http://www.ncbi.nlm.nih.gov/pubmed/16904274", "http://www.ncbi.nlm.nih.gov/pubmed/31857872", "http://www.ncbi.nlm.nih.gov/pubmed/29593919", "http://www.ncbi.nlm.nih.gov/pubmed/26947740", "http://www.ncbi.nlm.nih.gov/pubmed/15201655", "http://www.ncbi.nlm.nih.gov/pubmed/30776586", "http://www.ncbi.nlm.nih.gov/pubmed/10352221", "http://www.ncbi.nlm.nih.gov/pubmed/12613462", "http://www.ncbi.nlm.nih.gov/pubmed/27837588", "http://www.ncbi.nlm.nih.gov/pubmed/25024773", "http://www.ncbi.nlm.nih.gov/pubmed/26608488", "http://www.ncbi.nlm.nih.gov/pubmed/18366884", "http://www.ncbi.nlm.nih.gov/pubmed/11269682", "http://www.ncbi.nlm.nih.gov/pubmed/23267527", "http://www.ncbi.nlm.nih.gov/pubmed/19201139", "http://www.ncbi.nlm.nih.gov/pubmed/2915017", "http://www.ncbi.nlm.nih.gov/pubmed/25445385", "http://www.ncbi.nlm.nih.gov/pubmed/24997586", "http://www.ncbi.nlm.nih.gov/pubmed/18926295", "http://www.ncbi.nlm.nih.gov/pubmed/28831382", "http://www.ncbi.nlm.nih.gov/pubmed/32197716", "http://www.ncbi.nlm.nih.gov/pubmed/22293076", "http://www.ncbi.nlm.nih.gov/pubmed/29523423", "http://www.ncbi.nlm.nih.gov/pubmed/27364692", "http://www.ncbi.nlm.nih.gov/pubmed/7588825", "http://www.ncbi.nlm.nih.gov/pubmed/21242095", "http://www.ncbi.nlm.nih.gov/pubmed/26608484", "http://www.ncbi.nlm.nih.gov/pubmed/17205476", "http://www.ncbi.nlm.nih.gov/pubmed/31742204" ], "ideal_answer": [ "Capnocytophaga canimorsus infection is typically associated with dog bites, especially in asplenic or immunocompromised patients, and typically manifest as sepsis and/or bacteremia." ], "exact_answer": [ "Dog" ], "type": "factoid", "id": "6020a9f11cb411341a000080", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "INTRODUCTION: Capnocytophaga canimorsus infections are associated with dog bites, especially in asplenic or immunocompromised patients, and typically manifest as sepsis and/or bacteremia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30706413", "endSection": "abstract" }, { "offsetInBeginSection": 2065, "offsetInEndSection": 2219, "text": "CONCLUSION: C. canimorsus meningitis is a rare but increasingly important clinical entity occurring in patients of all ages, typically after dog exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30706413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "INTRODUCTION: The gram-negative bacteria known as Capnocytophaga canimorsus (C. canimorsus) is found in dog saliva and rarely can cause severe infection in humans following a bite or scratch. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30776586", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 557, "text": "PRESENTATION OF CASE: Here we describe the second ever published case of C. canimorsus bacteremia presenting with acute cholecystitis. The patient presented with epigastric pain and sepsis three weeks post domestic dog bite. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30776586", "endSection": "abstract" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1491, "text": "CONCLUSION: We strongly advocate blood cultures in patients who present with abdominal pain and sepsis, particularly when they have a recent history of animal bite. In cases of cholecystitis secondary to C. canimorsus it may be necessary to monitor the patient's progress more closely and treat with prolonged targeted antibiotic therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30776586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Being Licked by a Dog Can Be Fatal: Capnocytophaga canimorsus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31742204", "endSection": "title" }, { "offsetInBeginSection": 576, "offsetInEndSection": 920, "text": "LEARNING POINTS: Pet owners with banal, for instance flu-like, symptoms should urgently seek medical advice when symptoms are unusual.Capnocytophaga canimorsus infection should be considered and empirical antibiotic therapy immediately started or adjusted in the presence of purpura fulminans in the absence of animal bites or immunodeficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31742204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "BACKGROUND: Capnocytophaga canimorsus is a bacterium of the normal oral flora of dogs and cats. Human infection is caused by animal bite but is rarely observed, mainly in immunocompromised patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29523423", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 525, "text": "CASE REPORT: In the first case, we present a 69-year-old immunocompetent woman with septic shock derived from skin and soft tissue infection after a dog's bite.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29523423", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 855, "text": "In the second case, we present a 65-year-old immunocompetent man with meningitis after a dog's bite. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29523423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "A 70-year-old Caucasian woman was treated for Capnocytophaga canimorsus septicaemia. The source of bacteraemia was very likely to be her household pet, an Italian greyhound. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27364692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "INTRODUCTION: The gram-negative bacteria known as Capnocytophaga canimorsus (C. canimorsus) is found in dog saliva and rarely can cause severe infection in humans following a bite or scratch.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30776586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Capnocytophaga canimorsus bacteremia presenting with acute cholecystitis after a dog bite.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25445385", "endSection": "title" }, { "offsetInBeginSection": 190, "offsetInEndSection": 350, "text": "Capnocytophaga canimorsus (C. canimorsus) is a Gram-negative rod strongly associated with dog bites, and is known to cause life-threatening infection in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19201139", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 268, "text": "Capnocytophaga canimorsus, found in the normal oral flora of dogs, has the potential to cause conditions ranging from minor cellulitis to fatal sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23267527", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 760, "text": "Dog bite injuries can be also associated with Capnocytophaga canimorsus, an aggressive organism which can cause disseminated infections (sepsis) and death, particularly in immunocompromised individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26608484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Capnocytophaga canimorsus sepsis with purpura fulminans and symmetrical gangrene following a dog bite in a shelter employee", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15201655", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Capnocytophaga canimorsus bacteremia presenting with acute cholecystitis after a dog bite", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25445385", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Fatal dog bite in the absence of significant trauma: Capnocytophaga canimorsus infection and unexpected death", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20407357", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Newly named in 1989, Capnocytophaga canimorsus is a bacterial pathogen found in the saliva of healthy dogs and cats, and is transmitted to humans principally by dog bites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828064", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 323, "text": "The species Capnocytophaga canimorsus is particularly associated with dog bites and is known to cause endocarditis, meningitis, and sepsis in the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31857872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after dog bites.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828064", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Capnocytophaga canimorsus is a gram-negative rod that can be transmitted primarily by dog bites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28831382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Newly named in 1989, Capnocytophaga canimorsus is a bacterial pathogen found in the saliva of healthy dogs and cats, and is transmitted to humans principally by dog bites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "[Severe sepsis after dog bite caused by Capnocytophaga canimorsus].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26608488", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Described in this study is the case of a 53-year-old woman who developed a life-threatening infection caused by the bacterium Capnocytophaga canimorsus (C. canimorsus), subsequent to being bitten by a dog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21242095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Capnocytophaga canimorsis a cause of septicaemia following a dog bite: a case review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21242095", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Capnocytophaga canimorsus \u2013 an underestimated danger after dog or cat bite \u2013 review of literature", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27837588", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Capnocytophaga canimorsus, commonly transmitted by dog bites, can cause severe sepsis, and the mortality rate is very high. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32197716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Capnocytophaga canimorsus, a commensal bacterium from dogs' mouths, can cause septicemia or meningitis in humans through bites or scratches. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17205476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "BACKGROUND: Capnocytophaga canimorsus is a commensal bacterium found in the saliva of dogs and cats. Clinically significant infections in humans after a bite are often associated with the presence of immune deficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24997586", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "C. canimorsus and C. cynodegmi are dog and cat commensals which can be transmitted to humans via bites or scratches and can cause sepsis, meningitis, endocarditis, and eye- or wound infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26947740", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Capnocytophaga canimorsus is a commensal bacterium from the canine oral flora, which can cause septicemia or meningitis in humans upon bite wound infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18926295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "A 66-year-old man developed a hemolytic uremic syndrome (HUS) with acute renal failure, thrombocytopenia, fragmented red cells in the blood film and elevated serum LDH following a capnocytophaga canimorsus (DF-2) infection after a dog bite. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11269682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Capnocytophaga canimorsus is a fastidious, slow-growing, gram-negative, rod-shaped bacterium that belongs to the normal oral flora of dogs and cats. Human septicemic infections are associated with a high mortality; most cases occur in immunocompromised patients with a history of dog bite. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7588825", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Capnocytophaga canimorsus has been recognized as an opportunistic pathogen causing systemic infections in immunocompromised individuals. It is part of the normal oral flora of the dog, and can be responsible for localized wound infections in humans in consequence of bites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18366884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Capnocytophaga canimorsus causes dog-bite wound induced sepsis in adults, but infection may follow mucous membrane exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12613462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Hemolytic uremic syndrome due to Capnocytophaga canimorsus bacteremia after a dog bite.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10352221", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Capnocytophaga canimorsus was cultured from an infected, dog-inflicted bite wound in a pet rabbit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16904274", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 452, "text": "We describe an interesting case presenting with hypertensive emergency and type 2 myocardial infarction resulting from Pheochromocytoma associated with Capnocytophaga canimorsus infection from a dog bite. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25024773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Capnocytophaga canimorsus is a Gram-negative bacilli that is part of the normal oral flora of dogs and some cats; it is well known to cause septicemia and endocarditis after their bite. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29593919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Capnocytophaga canimorsus is a gram-negative bacterial species hosted in the oral cavity of dogs. C. canimorsus can cause sepsis, meningitis and endocarditis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22293076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Capnocytophaga canimorsus sp. nov. (formerly CDC group DF-2), a cause of septicemia following dog bite, and C. cynodegmi sp. nov., a cause of localized wound infection following dog bite", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2915017", "endSection": "title" } ] }, { "body": "What is the function of lysozyme?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32730854", "http://www.ncbi.nlm.nih.gov/pubmed/31790908", "http://www.ncbi.nlm.nih.gov/pubmed/31989035" ], "ideal_answer": [ "Lysozymes are an ancient group of antimicrobial enzymes of the innate immune system. Lysozyme activity is a marker of Paneth cell function." ], "exact_answer": [ "lysozyme is an antimicrobial enzyme." ], "type": "factoid", "id": "6032ba631cb411341a00014b", "snippets": [ { "offsetInBeginSection": 819, "offsetInEndSection": 871, "text": "Lysozyme activity (a marker of Paneth cell function)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31989035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Lysozymes are an ancient group of antimicrobial enzymes of the innate immune system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730854", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 230, "text": " It displays chitinase and lysozyme activity, which could be important for the defense against pathogenic fungi, insects and bacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31790908", "endSection": "abstract" } ] }, { "body": "Explain amniotic band syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31528593", "http://www.ncbi.nlm.nih.gov/pubmed/14607048", "http://www.ncbi.nlm.nih.gov/pubmed/3292449", "http://www.ncbi.nlm.nih.gov/pubmed/15067893", "http://www.ncbi.nlm.nih.gov/pubmed/21080173", "http://www.ncbi.nlm.nih.gov/pubmed/29653043", "http://www.ncbi.nlm.nih.gov/pubmed/8851988", "http://www.ncbi.nlm.nih.gov/pubmed/7124837", "http://www.ncbi.nlm.nih.gov/pubmed/26159096", "http://www.ncbi.nlm.nih.gov/pubmed/9804264", "http://www.ncbi.nlm.nih.gov/pubmed/32335054", "http://www.ncbi.nlm.nih.gov/pubmed/23248551", "http://www.ncbi.nlm.nih.gov/pubmed/17560504", "http://www.ncbi.nlm.nih.gov/pubmed/29634607", "http://www.ncbi.nlm.nih.gov/pubmed/29876159", "http://www.ncbi.nlm.nih.gov/pubmed/9444044", "http://www.ncbi.nlm.nih.gov/pubmed/24779260", "http://www.ncbi.nlm.nih.gov/pubmed/21837919", "http://www.ncbi.nlm.nih.gov/pubmed/31516628", "http://www.ncbi.nlm.nih.gov/pubmed/8360442" ], "ideal_answer": [ "Amniotic band syndrome (ABS) is a rare congenital disease with variable manifestations ranging from simple constriction rings at the extremities to major defects such as exencephaly.", "Amniotic band syndrome is a rare congenital disorder caused by entrapment of fetal parts in fibrous amniotic bands.", "Amniotic band syndrome is a rare congenital disorder characterized by the association of bilateral microtia, aplasia or hypoplasia of the upper aerodigestive tract, and severe pre- and postnatal growth retardation.", "Amniotic band syndrome, also known as constriction ring syndrome, happens when fibrous bands of the amniotic sac (the lining inside the uterus that contains a fetus) get tangled around a developing fetus. In rare cases, the bands wrap around the fetus' head or umbilical cord.", "Amniotic band sequence (ABS) is an uncommon and heterogeneous congenital disorder caused by entrapment of fetal parts by fibrous amniotic bands, causing distinctive structural abnormalities involving limbs, trunk, and craniofacial regions.", "Amniotic band syndrome is a rare congenital disorder caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero that presents with complex multisystem anomalies.", "yes, amniotic band syndrome is an uncommon and heterogeneous congenital disorder caused by entrapment of fetal parts by fibrous amniotic bands, causing distinctive structural abnormalities involving limbs, trunk, and craniofacial regions.", "Amniotic band syndrome is a rare congenital disorder characterized by the association of bilateral microtia, aplasia or hypoplasia of the collagen fibers of the fascia of the palm, and severe pre- and postnatal growth retardation.", "abs is an uncommon and heterogeneous congenital disorder caused by entrapment of fetal parts by fibrous amniotic bands, causing distinctive structural abnormalities involving limbs, trunk, and craniofacial regions. the incidence ranges between 1/1200 and 1/15,000 live births, but is higher in stillbirths and previable fetuses." ], "type": "summary", "id": "601ec6e11cb411341a000064", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 170, "text": "Amniotic band syndrome is a rare congenital disorder with clinical presentation of constricting\nbands in different parts of extremities or whole extremities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29653043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Amniotic band syndrome is a rare congenital disorder caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero that presents with complex multisystem anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29634607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Amniotic band syndrome (ABS) is a rare congenital disease with variable manifestations ranging from simple constriction rings at the extremities to major defects such as exencephaly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31516628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Amniotic band sequence (ABS) is an uncommon and heterogeneous congenital disorder caused by entrapment of fetal parts by fibrous amniotic bands, causing distinctive structural abnormalities involving limbs, trunk, and craniofacial regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31528593", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Amniotic band syndrome is a well described clinical entity presenting with deformities of the limbs, thorax, craniofacial skeleton, soft tissues and umbilical cord, but it still lacks a precise definition and a coherent hypothesis for its pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9804264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Amniotic band syndrome (ABS) is a fetal congenital malformation, affecting mainly the limbs, but also the craniofacial area and internal organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24779260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Amniotic band syndrome is a well described clinical entity presenting with deformities of the limbs, thorax, craniofacial skeleton, soft tissues and umbilical cord, but it still lacks a precise definition and a coherent hypothesis for its pathogenesis. We re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9804264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Amniotic band syndrome is a group of sporadic congenital anomalies that involve the limbs, craniofacial regions and trunk, ranging from simple digital band constriction to complex craniofacial and central nervous system abnormalities. Pla", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26159096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "BACKGROUND: The amniotic band syndrome is a collection of fetal malformations associated with fibrous bands that appear to entrap or entangle various fetal parts in utero and can affect any organ or system and cause a single or multiple ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14607048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "The amniotic band syndrome is a collection of fetal malformations associated with fibrous bands that appear to entangle or entrap various fetal parts in utero, leading to deformation, malformation, or disruption. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7124837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Amniotic band syndrome is a rare congenital disorder caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero that presents with complex multisystem anomalies. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29634607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Amniotic band syndrome is a sporadic condition that occurs in approximately 1:1200 to 1:15,000 live births and that may result in amputations, constrictions and other deformities of the fetus. Al", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9444044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Background: Amniotic Band Syndrome is a clinical constellation of congenital anomalies characterized by constricting rings, tissue synechiae and amputation of body parts distal to the constricti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29876159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Amniotic band syndrome is a rare pathology which involves a group of fetal malformations due to the formation of bands between the fetus and the extraembryonic derivatives. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8360442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "BACKGROUND: Amniotic band syndrome consists of a wide spectrum of clinical manifestations attributed to entanglement and disruption of different developing parts of the embryo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21080173", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "BACKGROUND: Postprocedural amniotic band disruption sequence is a condition that is associated with intrauterine interventions, and it is characterized by a constriction of the limbs or umbilical cord by fibrous strands, leading to edema, amputation, and/or fetal demise", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32335054", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The amniotic band syndrome is a collection of fetal malformations associated with fibrous bands that appear to entangle or entrap various fetal parts in utero, leading to deformation, malformation, or disruption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7124837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The amniotic band syndrome (ABS) refers to the infrequent occurrence of congenital deformities presumably due to fetal entanglement in strands of ruptured amniotic sac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3292449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The amniotic band syndrome is a collection of congenital deformities presumably due to rupture of amniotic sac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8851988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Amniotic band syndrome is an uncommon congenital pathological condition that may lead to malformations and foetal-infant death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21837919", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The amniotic (constriction) band syndrome is characterized by distal ring constrictions, intrauterine amputations, and acrosyndactyly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17560504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Amniotic band syndrome is a collection of fetal congenital malformations, affecting mainly the limbs, but also the craniofacial area and internal organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15067893", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 346, "text": "Amniotic band syndrome is another rare congenital malformation with ring-like constriction bands in the limbs, head, face or trunk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23248551", "endSection": "abstract" } ] }, { "body": "Which are the main advantages of kallisto against similar methodologies?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27043002", "http://www.ncbi.nlm.nih.gov/pubmed/28484260", "http://www.ncbi.nlm.nih.gov/pubmed/28868134", "http://www.ncbi.nlm.nih.gov/pubmed/28361706", "http://www.ncbi.nlm.nih.gov/pubmed/28096075", "http://www.ncbi.nlm.nih.gov/pubmed/31357172", "http://www.ncbi.nlm.nih.gov/pubmed/30168903" ], "ideal_answer": [ "Kallisto is a pseudo-alignment algorithm, which is a way of quantifying RNA-sequencing. It's used in RNA-seq because it's much faster and more efficient than other methodologies.", "Kallisto is two orders of magnitude faster than similar methodologies. It uses a novel efficient approach to perform this analysis and to calculate informative metrics at each depth required to inform a broad range of functional and evolutionary studies. It improves performance and speed of RNA sequencing analysis of large data sets.", "kallisto, an RNA-seq quantification program that is two orders of magnitude faster than previous approaches and achieves similar accuracy.", "kallisto is an RNA-seq quantification program that is two orders of magnitude faster than previous approaches and achieves similar accuracy. Kallisto pseudoaligns reads to a reference, producing a list of transcripts that are compatible with each read while avoiding alignment of individual bases." ], "exact_answer": [ [ "pseudoalignment" ], [ "speed" ], [ "avoids alignment of individual bases" ] ], "type": "list", "id": "5fdb420fa43ad3127800001f", "snippets": [ { "offsetInBeginSection": 946, "offsetInEndSection": 1138, "text": "Results show that count data gives poor parameter estimations, large intercepts and high inter-sample variability; while TPM value from Kallisto and Salmon shows high linearity in all analyses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361706", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1355, "text": "Salmon and Kallisto TPM data gives the best fit to the linear model studied. This suggests that TPM values estimated from Salmon and Kallisto are the ideal RNA-seq measurements for deconvolution studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28361706", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 833, "text": " Similarly, new pseudo-alignment-based protocols like Kallisto and Sleuth reduce runtime and improve performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30168903", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The recently introduced Kallisto pseudoaligner has radically simplified the quantification of transcripts in RNA-sequencing experiments.\u00a0", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868134", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 1081, "text": "Arkas-Quantification deploys Kallisto for parallel cloud computations and is conveniently integrated downstream from the BaseSpace Sequence Read Archive (SRA) import/conversion application titled SRA Import.\u00a0 Arkas-Analysis annotates the Kallisto results by extracting structured information directly from source FASTA files with per-contig metadata, calculates the differential expression and gene-set enrichment analysis on both coding genes and transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868134", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 778, "text": "RNA-sequencing reads were processed using five workflows (Tophat-HTSeq, Tophat-Cufflinks, STAR-HTSeq, Kallisto and Salmon) and resulting gene expression measurements were compared to expression data generated by wet-lab validated qPCR assays for all protein coding genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28484260", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 306, "text": "kallisto, an RNA-seq quantification program that is two orders of magnitude faster than previous approaches and achieves similar accuracy. Kallisto pseudoaligns reads to a reference, producing a list of transcripts that are compatible with each read while avoiding alignment of individual bases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043002", "endSection": "abstract" }, { "offsetInBeginSection": 722, "offsetInEndSection": 1074, "text": "It features six independent core-workflows comprising the state-of-the-art technology with dozens of popular cutting-edge tools such as Tophat-Cufflink-Cuffdiff, Subread-featureCounts-DESeq2, STAR-RSEM-EBSeq, Bowtie-eXpress-edgeR, kallisto-sleuth, HISAT-StringTie-Ballgown, and embeds itself in Snakemake, which is a modern pipeline management system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28096075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "We present kallisto, an RNA-seq quantification program that is two orders of magnitude faster than previous approaches and achieves similar accuracy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043002", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 424, "text": "se kallisto to analyze 30 million unaligned paired-end RNA-seq reads in <10 min on a standard laptop computer. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043002", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 306, "text": "Kallisto pseudoaligns reads to a reference, producing a list of transcripts that are compatible with each read while avoiding alignment of individual bases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The recently introduced Kallisto pseudoaligner has radically simplified the quantification of transcripts in RNA-sequencing experiments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28868134", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 833, "text": "Similarly, new pseudo-alignment-based protocols like Kallisto and Sleuth reduce runtime and improve performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30168903", "endSection": "abstract" } ] }, { "body": "What methodology does the HercepTest use?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32256703" ], "ideal_answer": [ "The HercepTest is immunohistochemistry based." ], "exact_answer": [ "immunohistochemistry", "ICH" ], "type": "factoid", "id": "606c34ff94d57fd879000078", "snippets": [ { "offsetInBeginSection": 523, "offsetInEndSection": 677, "text": " The expression of HER2 was determined by immunohistochemistry (IHC) using DAKO-HercepTest\u2122 and gene amplification with DuoCISH using a DAKO-DuoCISH kit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32256703", "endSection": "abstract" } ] }, { "body": "Which R/Bioconductor package has been developed for gene expression signature searching?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33068417" ], "ideal_answer": [ "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (ESE) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results.", "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (ESE) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. To identify which processes are predominantly modulated in the GESS results, FEA methods are combined with drug-target network visualization tools. The provided analysis tools are useful for studying the effects of genetic, chemical and environmental perturbations on biological systems, as well as searching single cell GES databases to identify novel network connections or cell types", "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results.", "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. The provided analysis tools are useful for studying the effects of genetic, chemical and environmental perturbations on biological systems, as well as searching single cell GES databases to identify novel network connections or cell types.", "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (ANS) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results." ], "exact_answer": [ "SignatureSearch" ], "type": "factoid", "id": "601ebde11cb411341a00005d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "signatureSearch: environment for gene expression signature searching and functional interpretation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33068417", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1422, "text": "signatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. In a typical GES search (GESS), a query GES is searched against a database of GESs obtained from large numbers of measurements, such as different genetic backgrounds, disease states and drug perturbations. Database matches sharing correlated signatures with the query indicate related cellular responses frequently governed by connected mechanisms, such as drugs mimicking the expression responses of a disease. To identify which processes are predominantly modulated in the GESS results, we developed specialized FEA methods combined with drug-target network visualization tools. The provided analysis tools are useful for studying the effects of genetic, chemical and environmental perturbations on biological systems, as well as searching single cell GES databases to identify novel network connections or cell types. The signatureSearch software is unique in that it provides access to an integrated environment for GESS/FEA routines that includes several novel search and enrichment methods, efficient data structures, and access to pre-built GES databases, and allowing users to work with custom databases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33068417", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by Upadacitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31287230", "http://www.ncbi.nlm.nih.gov/pubmed/31781755", "http://www.ncbi.nlm.nih.gov/pubmed/31867699", "http://www.ncbi.nlm.nih.gov/pubmed/29688617", "http://www.ncbi.nlm.nih.gov/pubmed/31130260", "http://www.ncbi.nlm.nih.gov/pubmed/30973649", "http://www.ncbi.nlm.nih.gov/pubmed/31654328", "http://www.ncbi.nlm.nih.gov/pubmed/31448433", "http://www.ncbi.nlm.nih.gov/pubmed/31692920", "http://www.ncbi.nlm.nih.gov/pubmed/31317509", "http://www.ncbi.nlm.nih.gov/pubmed/31378969", "http://www.ncbi.nlm.nih.gov/pubmed/32648334", "http://www.ncbi.nlm.nih.gov/pubmed/32776305", "http://www.ncbi.nlm.nih.gov/pubmed/32044319", "http://www.ncbi.nlm.nih.gov/pubmed/31786154", "http://www.ncbi.nlm.nih.gov/pubmed/28762476", "http://www.ncbi.nlm.nih.gov/pubmed/30633369", "http://www.ncbi.nlm.nih.gov/pubmed/29908670", "http://www.ncbi.nlm.nih.gov/pubmed/28503781", "http://www.ncbi.nlm.nih.gov/pubmed/31401212", "http://www.ncbi.nlm.nih.gov/pubmed/33129109", "http://www.ncbi.nlm.nih.gov/pubmed/30725185", "http://www.ncbi.nlm.nih.gov/pubmed/31327403", "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "http://www.ncbi.nlm.nih.gov/pubmed/29672874", "http://www.ncbi.nlm.nih.gov/pubmed/29908669", "http://www.ncbi.nlm.nih.gov/pubmed/29076110", "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "http://www.ncbi.nlm.nih.gov/pubmed/28765121", "http://www.ncbi.nlm.nih.gov/pubmed/30500075", "http://www.ncbi.nlm.nih.gov/pubmed/32530345" ], "ideal_answer": [ "Upadacitinib is a Janus kinase 1 inhibitor developed for treatment of moderate to severe rheumatoid arthritis.", "Upadacitinib is a Janus kinase 1 inhibitor under development for the treatment of several inflammatory disorders including rheumatoid arthritis." ], "exact_answer": [ "Janus kinase 1" ], "type": "factoid", "id": "601c317a1cb411341a000014", "snippets": [ { "offsetInBeginSection": 1255, "offsetInEndSection": 1554, "text": "We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28765121", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 463, "text": "Upadacitinib is a Janus kinase 1 inhibitor currently being evaluated in phase III rheumatoid arthritis trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28762476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND AND OBJECTIVES: Upadacitinib is a janus kinase (JAK) 1 inhibitor being developed for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29076110", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1163, "text": "RESULTS: In randomised controlled trials primary efficacy endpoints were met for tofacitinib (JAK 1/3 inhibitor-phase III), upadacitinib (JAK 1 inhibitor-phase II) and AJM300 (\u03b14-integrin antagonist-phase II) in ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29672874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Upadacitinib is a Janus kinase 1 inhibitor under development for the treatment of several inflammatory disorders including rheumatoid arthritis (RA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688617", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 371, "text": "Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "BACKGROUND\nPhase 2 studies with upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, have shown safety and efficacy in the treatment of patients with active rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29908670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND\nUpadacitinib is a selective inhibitor of Janus kinase 1 and was efficacious in phase 2 studies in patients with moderate-to-severe rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29908669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Upadacitinib is a novel selective oral Janus kinase 1 (JAK) inhibitor being developed for treatment of several inflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30500075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND AND OBJECTIVES\nUpadacitinib is a janus kinase (JAK) 1 inhibitor being developed for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29076110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "AIMS\nUpadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503781", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1168, "text": "RESULTS\nIn randomised controlled trials primary efficacy endpoints were met for tofacitinib (JAK 1/3 inhibitor-phase III), upadacitinib (JAK 1 inhibitor-phase II) and AJM300 (\u03b14-integrin antagonist-phase II) in ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29672874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "AIMS Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND Upadacitinib is a selective inhibitor of Janus kinase 1 and was efficacious in phase 2 studies in patients with moderate-to-severe rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29908669", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 316, "text": "Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1321, "text": "Expert commentary: Upadacitinib has displayed a rapid and favorable efficacy profile in RA but despite being a selective JAK1 inhibitor appears to have a similar safety profile to less-selective Jakinibs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND AND OBJECTIVES Upadacitinib is a janus kinase (JAK) 1 inhibitor being developed for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29076110", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Upadacitinib is a Janus kinase 1 inhibitor under development for the treatment of several inflammatory disorders including rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29688617", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 463, "text": "Areas covered: In this paper, we review a newly developed oral selective JAK inhibitor, upadacitinib for the treatment of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 337, "text": "Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "AIMS: Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503781", "endSection": "abstract" }, { "offsetInBeginSection": 1138, "offsetInEndSection": 1342, "text": "Expert commentary: Upadacitinib has displayed a rapid and favorable efficacy profile in RA but despite being a selective JAK1 inhibitor appears to have a similar safety profile to less-selective Jakinibs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503781", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503781", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 442, "text": "Areas covered: In this paper, we review a newly developed oral selective JAK inhibitor, upadacitinib for the treatment of RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "OBJECTIVES: We assessed the relative efficacy and safety of once-daily administration of 15 and 30\u202fmg upadacitinib (a\u00a0JAK1-selective inhibitor) in patients with active rheumatoid arthritis (RA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30725185", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 797, "text": " In contrast, efficacy of filgotinib, a selective JAK1 inhibitor, in CD patients was demonstrated in the randomized, double-blinded, placebo-controlled phase II FITZROY study. Upadacitinib also showed promising results in a phase II trial in moderate to severe CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31781755", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Upadacitinib is a Janus kinase\u00a01 inhibitor developed for treatment of moderate to severe rheumatoid arthritis (RA) and was recently approved by the US Food and Drug Administration for this indication in adults who have had an inadequate response or intolerance to methotrexate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31867699", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 292, "text": "BJECTIVE: We sought to evaluate the safety and efficacy of multiple doses of the selective Janus kinase 1 inhibitor upadacitinib in patients with moderate to severe atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31786154", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The aim of this study was to characterize the effects of upadacitinib, a Janus kinase 1 inhibitor, on in vivo activity of different cytochrome P450 (CYP) enzymes using a cocktail approach. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31378969", "endSection": "abstract" }, { "offsetInBeginSection": 990, "offsetInEndSection": 1088, "text": "thods: Structure-based hypotheses were used to design the JAK1 selective inhibitor upadacitinib. J", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "endSection": "abstract" }, { "offsetInBeginSection": 938, "offsetInEndSection": 1169, "text": "S: In randomised controlled trials primary efficacy endpoints were met for tofacitinib (JAK 1/3 inhibitor-phase III), upadacitinib (JAK 1 inhibitor-phase II) and AJM300 (\u03b14-integrin antagonist-phase II) in ulcerative colitis. Ozani", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29672874", "endSection": "abstract" }, { "offsetInBeginSection": 1115, "offsetInEndSection": 1459, "text": "Both these new compounds are active on the majority of four JAK family members (JAK1, JAK2, JAK3, and TYK2), whereas the most recent emerging approach is directed toward the development of JAK1 selective inhibitors (upadacitinib and filgotinib) with the aim to improve the safety profile by minimizing the effects on JAK3 and, especially, JAK2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692920", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 757, "text": "Upadacitinib (ABT-494) is a selective JAK1 inhibitor that was engineered to address the hypothesis that greater JAK1 selectivity over other JAK family members will translate into a more favorable benefit:risk profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 516, "text": "Upadacitinib is a JAK inhibitor engineered to be selective for JAK1, and has recently been approved for use in patients with moderate-to-severe RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32530345", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 990, "text": "e. Upadacitinib selectively targets JAK1 dependent disease drivers such as IL-6 and IFN\u03b3, while reducing effects on reticulocytes and natural killer (NK) cells, which potentially contributed to the tolerability issues of tofacitinib.Me", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "endSection": "abstract" }, { "offsetInBeginSection": 535, "offsetInEndSection": 755, "text": "mia. Upadacitinib (ABT-494) is a selective JAK1 inhibitor that was engineered to address the hypothesis that greater JAK1 selectivity over other JAK family members will translate into a more favorable benefit:risk profil", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "endSection": "abstract" }, { "offsetInBeginSection": 998, "offsetInEndSection": 1087, "text": "tructure-based hypotheses were used to design the JAK1 selective inhibitor upadacitinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 178, "text": "We evaluated the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, in a randomized trial of patients with Crohn's disease (CD).M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32044319", "endSection": "abstract" }, { "offsetInBeginSection": 746, "offsetInEndSection": 1065, "text": "sk profile. Upadacitinib selectively targets JAK1 dependent disease drivers such as IL-6 and IFN\u03b3, while reducing effects on reticulocytes and natural killer (NK) cells, which potentially contributed to the tolerability issues of tofacitinib.Methods: Structure-based hypotheses were used to design the JAK1 selective in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "AIMS: Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory diso", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28503781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Upadacitinib is a selective Janus kinase (JAK) 1 inhibitor being developed for treatment of rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31448433", "endSection": "abstract" }, { "offsetInBeginSection": 1727, "offsetInEndSection": 1837, "text": "o physiological consequences. Upadacitinib is ~\u200960 fold selective for JAK1 over JAK2, and\u2009>\u2009100 fold selective", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Preferential Inhibition of JAK1 Relative to JAK3 by Upadacitinib: Exposure-Response Analyses of Ex Vivo Data From 2 Phase 1 Clinical Trials and Comparison to Tofacitinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31448433", "endSection": "title" }, { "offsetInBeginSection": 804, "offsetInEndSection": 959, "text": "Here, we demonstrated that Upadacitinib, a JAK-1 inhibitor, inhibited the proliferation of cytokine-dependent ATL cell lines and the expression of p-STAT5.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33129109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Selective JAK1 Inhibitors for the Treatment of Atopic Dermatitis: Focus on Upadacitinib and Abrocitinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32776305", "endSection": "title" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1010, "text": "Upadacitinib and abrocitinib are oral small molecules that inhibit the JAK/STAT pathway by selectively blocking JAK1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32776305", "endSection": "abstract" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1711, "text": "Several more selective JAK-1 inhibitors, including filgotinib and upadacitinib, have also shown positive results in phase II studies and are currently enrolling in phase III development programs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31317509", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 720, "text": "Emerging data with selective JAK1 inhibitors upadacitinib and filgotinib looks very promising", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31401212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 302, "text": "OBJECTIVE: To evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1-selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31287230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "BACKGROUND: Phase 2 studies with upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, have shown safety and efficacy in the treatment of patients with active rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29908670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: Upadacitinib is a selective inhibitor of Janus kinase 1 and was efficacious in phase 2 studies in patients with moderate-to-severe rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29908669", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 330, "text": "Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30394138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Upadacitinib is a selective Janus Kinase 1 inhibitor which is being developed for the treatment of several inflammatory diseases including rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31654328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Upadacitinib is a novel selective Janus kinase 1 inhibitor developed for treatment of rheumatoid arthritis and other autoimmune diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30633369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Upadacitinib is a selective Janus kinase 1 inhibitor being developed for the treatment of several inflammatory autoimmune diseases, including rheumatoid arthritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30973649", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "BACKGROUND: Upadacitinib, an oral Janus kinase (JAK)1-selective inhibitor, showed efficacy in combination with stable background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis who had an inadequate response to DMARDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31130260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "This phase 1 study characterized the effect of multiple doses of upadacitinib, an oral Janus kinase 1 selective inhibitor, on the pharmacokinetics of the cytochrome P450 (CYP) 2B6 substrate bupropion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648334", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 431, "text": "To date, three JAK inhibitors have been tested in patients with moderate-to-severe CD: tofacitinib (pan-JAK inhibitor), filgotinib (JAK1 inhibitor) and upadacitinib (JAK1 inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31327403", "endSection": "abstract" } ] }, { "body": "What is known about natriuretic peptide receptor A?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32433050", "http://www.ncbi.nlm.nih.gov/pubmed/33200806" ], "ideal_answer": [ "Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure.\nThe natriuretic peptide receptor A (NPRA), also known as NPR1 or guanylyl cyclase A, binds ANP and BNP to initiate transmembrane signal transduction by elevating the intracellular levels of cyclic guanosine monophosphate." ], "type": "summary", "id": "606b61f794d57fd879000068", "snippets": [ { "offsetInBeginSection": 138, "offsetInEndSection": 359, "text": "The natriuretic peptide receptor A (NPRA), also known as NPR1 or guanylyl cyclase A, binds ANP and BNP to initiate transmembrane signal transduction by elevating the intracellular levels of cyclic guanosine monophosphate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33200806", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1135, "text": "The results of this study indicated that NPRA may play a role in cardiac metabolism, which could be mediated by circRNA through endogenous competition mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33200806", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 205, "text": "Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32433050", "endSection": "abstract" } ] }, { "body": "What is the mode of action of dexamethasone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31547289", "http://www.ncbi.nlm.nih.gov/pubmed/32133644", "http://www.ncbi.nlm.nih.gov/pubmed/23511350", "http://www.ncbi.nlm.nih.gov/pubmed/29449600", "http://www.ncbi.nlm.nih.gov/pubmed/25347463", "http://www.ncbi.nlm.nih.gov/pubmed/32262373", "http://www.ncbi.nlm.nih.gov/pubmed/26496078", "http://www.ncbi.nlm.nih.gov/pubmed/28515280", "http://www.ncbi.nlm.nih.gov/pubmed/19390558", "http://www.ncbi.nlm.nih.gov/pubmed/30485523", "http://www.ncbi.nlm.nih.gov/pubmed/26891836", "http://www.ncbi.nlm.nih.gov/pubmed/21715273", "http://www.ncbi.nlm.nih.gov/pubmed/8559285", "http://www.ncbi.nlm.nih.gov/pubmed/8530259", "http://www.ncbi.nlm.nih.gov/pubmed/8523985", "http://www.ncbi.nlm.nih.gov/pubmed/14965196", "http://www.ncbi.nlm.nih.gov/pubmed/9891987", "http://www.ncbi.nlm.nih.gov/pubmed/7503523" ], "ideal_answer": [ "Glucocorticoids like Dexamethasone have a number of modes of action. While these drugs are used to reduce inflammation, Dexamethasone can also induce apoptosis thru initiation of autophagy, activate glucocorticoid receptors in the treatment of uveitic edema, alter gene expression in allergic asthma prevent tachycardia-induced ionic remodeling by reduction of atrial sodium current I(Na), increase gut permeability and suppress inflammation. in addition, Dexamethasone (Dex) can enhance BMP-2-induced osteoblast differentiation and can differentially modulated dendritic cell maturation and TREM1 signaling pathways in GM-CSF-treated and M-CSF-treated monocytes. Dexamethasone can be used for pain management", "yes, dexamethasone is used to treat acute graft-versus-host disease (agvhd) due to its immunosuppressive activity.", "Dexamethasone (Dex), a synthetic glucocorticoid (GC), in feed has been shown to increase gut permeabilit" ], "type": "summary", "id": "601c0b071cb411341a000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19390558", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Glucocorticoids are fundamental drugs used in the treatment of lymphoid malignancies with apoptotic cell death as the hitherto proposed mechanism of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19390558", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 564, "text": "We show that dexamethasone induced autophagy upstream of apoptosis in acute lymphoblastic leukemia cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19390558", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1609, "text": "mpact of corticosteroids and statins on INa and its tachycardia-induced alterations also contribute to the mode of action of these substances in upstream treatment of atrial fibrillation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21715273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Glucocorticoids (GCs) are widely used to treat acute graft-versus-host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft-versus-leukemia (GvL) effect of the allogeneic T\u00a0cells contained in the graft.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32133644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Dexamethasone (Dex), a synthetic glucocorticoid (GC), in feed has been shown to increase gut permeabilit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31547289", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 877, "text": "Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice expressing a defective GR in the nonhematopoietic compartment or selectively lacking the GR in airway epithelial cells. Further, we found that an intact GR dimerization interface was a prerequisite for the suppression of AAI and airway hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to modulate gene expression in airway epithelial cells coincided with its potency to resolve AAI supports a crucial role for transcriptional regulation by the GR in this cell type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28515280", "endSection": "abstract" }, { "offsetInBeginSection": 1137, "offsetInEndSection": 1312, "text": "In reporter assays, dexamethasone and Palovarotene induced transcriptional activity of their respective GRE or RARE constructs and did not interfere with each other's pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26891836", "endSection": "abstract" }, { "offsetInBeginSection": 1671, "offsetInEndSection": 1952, "text": " In sum, corticosteroids and Palovarotene appear to block HO via common and distinct mechanisms. Most importantly, they directly or indirectly inhibit the recruitment of immune and inflammatory cells present at the affected site, thus alleviating the effects of key HO instigators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26891836", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Proteomic and Metabolomic Analyses Reveal Contrasting Anti-Inflammatory Effects of an Extract of Mucor Racemosus Secondary Metabolites Compared to Dexamethasone.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26496078", "endSection": "title" }, { "offsetInBeginSection": 744, "offsetInEndSection": 982, "text": "Potential effects on inflammatory processes were investigated by treating stimulated cells with M rac extracts and the effects were compared to the standard anti-inflammatory drug dexamethasone on the levels of the proteome and metabolome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26496078", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 279, "text": " Dexamethasone (Dex) with suitable dosage can enhance BMP-2-induced osteoblast differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32262373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Glucocorticoids (GCs) are potent anti-inflammatory drugs whose mode of action is complex and still debatable", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29449600", "endSection": "abstract" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1182, "text": "Transcriptomic and Ingenuity pathway analyses found that dexamethasone differentially modulated dendritic cell maturation and TREM1 signaling pathways in GM-CSF-treated and M-CSF-treated monocytes, two pathways known to be regulated by ERK1/2 activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29449600", "endSection": "abstract" }, { "offsetInBeginSection": 1071, "offsetInEndSection": 1195, "text": "the inability of dexamethasone to downregulate inflammation-induced proteins such as PTX3 and TSG6 was clearly demonstrated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25347463", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 470, "text": " dexamethasone to investigate their response to this antiphlogistic drug", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25347463", "endSection": "abstract" }, { "offsetInBeginSection": 677, "offsetInEndSection": 860, "text": "preoperative dose dexamethasone has been shown not only to be effective in reducing postoperative nausea and vomiting but also to improve recovery reduce pain and improve satisfaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23511350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Dexamethasone (Dex), a synthetic glucocorticoid (GC), in feed has been shown to increase gut permeability via stress-mediated mechanisms, but the exact mode of action on gut barrier function is not fully understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31547289", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 761, "text": "The mode of action of dexamethasone was not specifically investigated in our study; however, it may suppress neutrophil function and reduce ischemia-reperfusion injury in its shared ability with BW755C to reduce the formation of leukotrienes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8523985", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Glucocorticoids have been shown repeatedly to inhibit the release of prolactin (PRL) in the rat but their site and mode of action is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8559285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Dexamethasone inhibits nitric oxide-mediated cytotoxicity via effects on both macrophages and target cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8530259", "endSection": "title" }, { "offsetInBeginSection": 312, "offsetInEndSection": 583, "text": "o the pleiotropic mode of action exerted by glucocorticoids which include profound anti-inflammatory and immunosuppressive effects, direct inhibition on SMC proliferation and apoptosis, their potential in the prevention of restenosis has gained widespread interest. Over ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14965196", "endSection": "abstract" }, { "offsetInBeginSection": 881, "offsetInEndSection": 1129, "text": "fic mode of action of dexamethasone was not investigated; however, its anti-inflammatory effects were most likely responsible for the improvement of flap survival by suppressing the circulating neutrophil and decreasing reperfusion injury. Dexameth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7503523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "Glucocorticoids (GCs) influence a great variety of cellular functions by at least three important modes of action: the activation (or repression) of genes controlled by binding sites for the glucocorticoid receptor (GR), the induction of apoptosis in lymphocytes and the recently discovered cross-talk to other transcription factors such as NF-kappaB. In t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9891987", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1254, "text": "Dexamethasone activates signalling pathways involved in the differentiation of osteoblasts, for example, CXC-motif chemokine receptor type 4 and mitogen-activated protein kinases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30485523", "endSection": "abstract" } ] }, { "body": "What is the phenomenon described as \"complex coacervation\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32033133", "http://www.ncbi.nlm.nih.gov/pubmed/27161661", "http://www.ncbi.nlm.nih.gov/pubmed/21230139", "http://www.ncbi.nlm.nih.gov/pubmed/18592584", "http://www.ncbi.nlm.nih.gov/pubmed/24268195", "http://www.ncbi.nlm.nih.gov/pubmed/21377640", "http://www.ncbi.nlm.nih.gov/pubmed/26791895", "http://www.ncbi.nlm.nih.gov/pubmed/27633928", "http://www.ncbi.nlm.nih.gov/pubmed/30995741", "http://www.ncbi.nlm.nih.gov/pubmed/29265152", "http://www.ncbi.nlm.nih.gov/pubmed/32134099", "http://www.ncbi.nlm.nih.gov/pubmed/33230101", "http://www.ncbi.nlm.nih.gov/pubmed/31041391", "http://www.ncbi.nlm.nih.gov/pubmed/30384692", "http://www.ncbi.nlm.nih.gov/pubmed/25565379" ], "ideal_answer": [ "Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules. Impact of macromolecular crowding on RNA/spermine complex coacervation and oligonucleotide compartmentalization. The addition of PEG decreased both the amount of spermine required for phase separation and the coacervation temperature (TC).", " Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules. Impact of macromolecular crowding on RNA/spermine complex coacervation and oligonucleotide compartmentalization. The addition of PEG decreased both the amount of spermine required for phase separation and the coacervation temperature (TC).", "Charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules. The addition of PEG decreased both the amount of spermine required for phase separation and the coacoration temperature (TC).", " Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules.", "Recently, we reported a unique and nearly ubiquitous phenomenon of inducing simple and complex coacervation in solutions of a broad variety of individual and mixed amphiphiles and over a wide range of concentrations and mole fractions. Complex coacoration is an emerging liquid/liquid phase separation (LLPS) phenomenon that behaves as a membrane-less organelle in living cells.", "Complex coacervation is a phase separation process that is mediated by the charges of the components involved." ], "type": "summary", "id": "5fe3130fa43ad31278000040", "snippets": [ { "offsetInBeginSection": 276, "offsetInEndSection": 491, "text": " Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26791895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Impact of macromolecular crowding on RNA/spermine complex coacervation and oligonucleotide compartmentalization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29265152", "endSection": "title" }, { "offsetInBeginSection": 213, "offsetInEndSection": 339, "text": "The addition of PEG decreased both the amount of spermine required for phase separation and the coacervation temperature (TC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29265152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Complex coacervation is an emerging liquid/liquid phase separation (LLPS) phenomenon that behaves as a membrane-less organelle in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30995741", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 573, "text": "Complex coacervation is an electrostatically and entropically-driven associative liquid-liquid phase separation phenomenon that can result in the formation of bulk liquid phases, or the self-assembly of hierarchical, microphase separated materials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27633928", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 292, "text": "Inspired by natural organisms, we have designed an adhesive based on complex coacervation, a liquid-liquid phase separation phenomenon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32033133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Liquid-liquid phase separation leading to complex coacervation in a ternary system (oppositely charged polyion and macroion in a solvent) is discussed within the framework of a statistical thermodynamics model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21230139", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1668, "text": "This model has been successfully applied to study the coacervation phenomenon observed in aqueous Laponite (macroion)-gelatin (polyion) system where it was found that the coacervate volume fraction, \u03b4\u03a6{23}\u223c\u03c7{231}{2} (where \u03b4\u03a6{23} is the volume fraction of coacervates formed during phase separation).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21230139", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Complex coacervation is a phenomenon of phase separation that may occur in a solution of positively and negatively charged polyions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18592584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "There has been a resurgence of interest in complex coacervation, a form of liquid-liquid phase separation (LLPS) in systems of oppositely charged macroions, but very few reports describe the somewhat anomalous coacervation between acidic and basic proteins, which occurs under very narrow ranges of conditions. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25565379", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Oppositely charged polymers can undergo the process of complex coacervation, which refers to a liquid-liquid phase separation driven by electrostatic attraction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27161661", "endSection": "abstract" }, { "offsetInBeginSection": 1018, "offsetInEndSection": 1224, "text": "ize a transfer matrix formalism that describes a phase separation phenomenon known as \"complex coacervation\" and provide a theoretical framework to predict the phase behavior of charge sequences. This work ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31041391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Complex coacervation is a phenomenon of phase separation that may occur in a solution of positively and negatively charged polyions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18592584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Complex coacervation is an emerging liquid/liquid phase separation (LLPS) phenomenon that behaves as a membrane-less organelle in living cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30995741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "A review of the early development of the thermodynamics of the complex coacervation phase separation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21377640", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Coacervation was defined as the phenomenon in which a colloidal dispersion separated into colloid-rich (the coacervate), and colloid-poor phases, both with the same solvent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21377640", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 417, "text": "Complex coacervation covered the situation in which a mixture of two polymeric polyions with opposite charge separated into liquid dilute and concentrated phases, in the same solvent, with both phases, at equilibrium, containing both polyions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21377640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Complex coacervation is an associative liquid/liquid phase separation resulting in the formation of two liquid phases: a polymer-rich coacervate phase and a dilute continuous solvent phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24268195", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Complex coacervation is an associative, liquid-liquid phase separation that can occur in solutions of oppositely-charged macromolecular species, such as proteins, polymers, and colloids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32134099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "We address complex coacervation, the liquid-liquid phase separation of a solution of oppositely charged polyelectrolyte chains into a polyelectrolyte rich complex coacervate phase and a dilute aqueous phase, based on the general premise of spontaneous formation of polycation-polyanion complexes even in the homogeneous phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30384692", "endSection": "abstract" } ] }, { "body": "Which proteins does RG-7992 target?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33139537" ], "ideal_answer": [ "BFKB8488A is a bispecific antibody against FGFR1 and KLB." ], "exact_answer": [ [ "FGFR1" ], [ "KLB" ] ], "type": "list", "id": "602c17d41cb411341a000118", "snippets": [ { "offsetInBeginSection": 444, "offsetInEndSection": 703, "text": "Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33139537", "endSection": "abstract" } ] }, { "body": "Is there a role for TFII-I in megakaryopoiesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33101065" ], "ideal_answer": [ "Yes. TFII-I acts as a repressor of \u03b2-globin gene transcription and is implicated in the differentiation of erythrocytes into megakaryopoiesis. Mutations in exon 2 interfere with the synthesis of the full-length isoform of TF II-I and lead to the production of a shortened isoform, TFII, in erythroid cells. TF2-I has a role in embryonic development and differentiation of all eukaryotes but its physiological function is still unclear.", "Yes. TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. TFII-I acts as a repressor of \u03b2-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.", "Yes. The data show that TFII-I acts as a repressor of \u03b2-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.", "Yes. TFII-I acts as a repressor of \u03b2-globin gene transcription and it is implicated in the differentiation of erythrocytes and megakaryopoiesis. In fact, upregulation of TF II-I expression in mesenchymal stem cells increases both survival and angiogenesis and may therefore represent a novel and efficient therapeutic approach for modulating cell proliferation and differentiation." ], "exact_answer": "yes", "type": "yesno", "id": "6027f7171cb411341a0000ec", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "TFII-I/Gtf2i and Erythro-Megakaryopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33101065", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 904, "text": "TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. We conditionally deleted the TFII-I/Gtf2i gene in adult mice by tamoxifen induced Cre-recombination. Bone marrow cells revealed defects in erythro-megakaryopoiesis and an increase in expression of the adult \u03b2-globin gene. The data show that TFII-I acts as a repressor of \u03b2-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33101065", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the VAC regiment for Ewing's sarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/991106", "http://www.ncbi.nlm.nih.gov/pubmed/14521810", "http://www.ncbi.nlm.nih.gov/pubmed/7029293", "http://www.ncbi.nlm.nih.gov/pubmed/12441260", "http://www.ncbi.nlm.nih.gov/pubmed/31197128", "http://www.ncbi.nlm.nih.gov/pubmed/11531770", "http://www.ncbi.nlm.nih.gov/pubmed/7583389", "http://www.ncbi.nlm.nih.gov/pubmed/9053479", "http://www.ncbi.nlm.nih.gov/pubmed/29541566", "http://www.ncbi.nlm.nih.gov/pubmed/15626016", "http://www.ncbi.nlm.nih.gov/pubmed/20110048", "http://www.ncbi.nlm.nih.gov/pubmed/10742059", "http://www.ncbi.nlm.nih.gov/pubmed/2667789", "http://www.ncbi.nlm.nih.gov/pubmed/15613556", "http://www.ncbi.nlm.nih.gov/pubmed/26271204", "http://www.ncbi.nlm.nih.gov/pubmed/2016622" ], "ideal_answer": [ "VAC regiment for Ewing's sarcoma includes vincristine, actinomycin, cyclophosphamide." ], "exact_answer": [ [ "vincristine" ], [ "actinomycin" ], [ "cyclophosphamide" ] ], "type": "list", "id": "60274ec61cb411341a0000e5", "snippets": [ { "offsetInBeginSection": 508, "offsetInEndSection": 797, "text": "All underwent surgical exploration with a laminectomy and partial resection followed by adjuvant radiotherapy to a dose of 46-50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide) alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six cycles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11531770", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1853, "text": "For patients with localized, gross residual tumor, adding doxorubicin (DOX) to the combination of vincristine, dactinomycin, cyclophosphamide (VAC), and XRT did not significantly improve survival in 39 patients (62% alive at 10 years) compared with that of 24 patients treated with VAC and XRT without DOX (65% alive at 10 years, P = .93).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9053479", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 592, "text": "Patients with tumors in clinical groups II, III, and IV were treated with radiotherapy (XRT) and vincristine-dactinomycin (VA) or VA plus cyclophosphamide (VAC) +/- doxorubicin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2016622", "endSection": "abstract" }, { "offsetInBeginSection": 1112, "offsetInEndSection": 1431, "text": "Despite numerous molecular and biological studies during the past three decades, the chemotherapeutic regimen remains unchanged. This vincristine, actinomycin, cyclophosphamide (VAC) regime, described in Kilman, et al. (1973) and Koop, et al. (1963), has achieved limited success in controlling the progression of RMS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29541566", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 475, "text": "After the induction chemotherapy consisting of alternating vincristine, adriablastin, cyclophosphamide (VAC) and etoposide, ifosfamide with mesna protection (IE), a local treatment modality was chosen based on tumor and patient characteristics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15613556", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 375, "text": "Induction chemotherapy consisted of two cycles of 'VAC': vincristine (V), doxorubicin (A), cyclophosphamide (C) alternated with one cycle of 'VIAc': V, ifosfamide (I), actinomycin (Ac). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12441260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "Phase II studies using ifosfamide both alone and combined with vindesine and cisplatin have shown the effectiveness of this drug in patients with Ewing's sarcoma (ES) who had relapsed during VAC (vincristine, actinomycin, cyclosphosphamide)/VAd (vincristine, Adriamycin) therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2667789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Phase II studies using ifosfamide both alone and combined with vindesine and cisplatin have shown the effectiveness of this drug in patients with Ewing's sarcoma (ES) who had relapsed during VAC (vincristine, actinomycin, cyclosphosphamide)/VAd (vincristine, Adriamycin) therapy. In Novembe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2667789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "BACKGROUND: Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26271204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Vincristine, actinomycin D, and cyclophosphamide (VAC) were administered to 14 patients with Ewing's sarcoma. The pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/991106", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 812, "text": "Every patient received both types of G-CSF in different treatment courses of chemotherapy, which consisted of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE); vincristine, actinomycin D, and ifosfamide (VAI); or vincristine, actinomycin D, and cyclophosphamide (VAC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110048", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 685, "text": "VAC (vincristine, actinomycin D, and cyclophosphamide) regimens with anthracyclines resulted in better survival. Presence of distant metastases, large primary tumors, and pelvic localization were related to poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15626016", "endSection": "abstract" }, { "offsetInBeginSection": 1367, "offsetInEndSection": 1579, "text": "The effective treatment for sarcoma botryoides is wide excision with safe margin of 1-2 cm, followed by 6-12 cycles of vincristine, actinomycin D, and cyclophosphamide (VAC) regiment as an adjuvant chemotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31197128", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Cyclophosphamide dose escalation in combination with vincristine and actinomycin-D (VAC) in gross residual sarcoma. A pilot study without hematopoietic growth factor support evaluating toxicity and response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7583389", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 356, "text": "PURPOSE: The Intergroup Rhabdomyosarcoma Study (IRS) initiated an escalating-dose cyclophosphamide (Cyc) pilot without hematopoietic growth factor (HGF) support in combination with vincristine (Vcr) and actinomycin-D (Amd), known as VAC, to establish a Cyc dose with myelotoxicity comparable to an ifosfamide (Ifos), Vcr, and Amd combination regimen (VAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7583389", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 722, "text": "PROCEDURE: Standard chemotherapy consisted of etoposide/ifosfamide (VP16/IFOS) cycles, alternating with vincristine/dactinomycin/cyclophosphamide (VAC) cycles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10742059", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 540, "text": "The Intergroup Study was designed to determine if the addition of adriamycin (ADR) or bilateral pulmonary radiotherapy (RT) to vincristine, dactinomycin, and cyclophosphamide (VAC therapy) would improve survival and reduce local recurrences and metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7029293", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 649, "text": "Taking the lead from the use of vincristine, actinomycin-D, and cyclophosphamide (VAC) by Dr. Ruth Heyn, Dr. Harold Mauer and colleagues developed a more robust VAC as well as three similar drug regimens with hematopoietic growth factor support, which, in the context of surgery with or without radiotherapy, achieved a 3-year failure-free survival rate of 83% (IRS-IV) in nonmetastatic embryonal rhabdomyosarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14521810", "endSection": "abstract" } ] }, { "body": "Is YKL-40 used as a biomarker for Alzheimer's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31668967", "http://www.ncbi.nlm.nih.gov/pubmed/31794792", "http://www.ncbi.nlm.nih.gov/pubmed/32045356" ], "ideal_answer": [ "Yes,\ncerebrospinal fluid (CSF) YKL-40 levels were reported to be a promising candidate biomarker of glial inflammation in Alzheimer's disease (AD)." ], "exact_answer": "yes", "type": "yesno", "id": "604915581cb411341a00016a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Recently, cerebrospinal fluid (CSF) YKL-40 levels were reported to be a promising candidate biomarker of glial inflammation in Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31794792", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 595, "text": "Disease groups differed between them except AD versus FTD for YKL-40. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31668967", "endSection": "abstract" }, { "offsetInBeginSection": 1094, "offsetInEndSection": 1175, "text": "YKL-40 appears to be a more reliable biomarker in neurological diseases than NSE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32045356", "endSection": "abstract" } ] }, { "body": "On what chromosome is the gene for \"SILVER\" coat color found for the domestic cat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19398491" ], "ideal_answer": [ "Linkage mapping defined a genomic region for SILVER as a 3.3-Mb region, (95.87-99.21 Mb) on chromosome D2 in the domestic cat.", "the gene for \"silver\" coat color found for the domestic cat is located on chromosome d2." ], "exact_answer": [ "D2", "chromosome D2" ], "type": "factoid", "id": "601db60e1cb411341a000049", "snippets": [ { "offsetInBeginSection": 367, "offsetInEndSection": 472, "text": "Linkage mapping defined a genomic region for SILVER as a 3.3-Mb region, (95.87-99.21 Mb) on chromosome D2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398491", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 648, "text": "ge mapping defined a genomic region for SILVER as a 3.3-Mb region, (95.87-99.21 Mb) on chromosome D2, (peak logarithm of the odds = 10.5, = 0), which displays conserved synteny to a genomic interval between 118.58 and 121.85 Mb on chromosome 10 in the human genome. In the dom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398491", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 637, "text": "Linkage mapping defined a genomic region for SILVER as a 3.3-Mb region, (95.87-99.21 Mb) on chromosome D2, (peak logarithm of the odds = 10.5, = 0), which displays conserved synteny to a genomic interval between 118.58 and 121.85 Mb on chromosome 10 in the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19398491", "endSection": "abstract" } ] }, { "body": "Which lncRNAs are induced by heatshock?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27518140", "http://www.ncbi.nlm.nih.gov/pubmed/27257073", "http://www.ncbi.nlm.nih.gov/pubmed/26634309", "http://www.ncbi.nlm.nih.gov/pubmed/22976942", "http://www.ncbi.nlm.nih.gov/pubmed/30305397", "http://www.ncbi.nlm.nih.gov/pubmed/26142536", "http://www.ncbi.nlm.nih.gov/pubmed/29228702", "http://www.ncbi.nlm.nih.gov/pubmed/24002685" ], "ideal_answer": [ "Malat1, papas, long noncoding rnas, circrna, neat1, and mirna are induced by heat shock.", "Malat1, papas, long noncoding rnas, circrna, neat1 and mirna are induced by heathock.", "The Malat1 long non-coding RNA is upregulated by signalling through the PERK axis of unfolded protein response during flavivirus infection. Attenuation of pre-rRNA synthesis in response to heat stress is accompanied by upregulation of PAPAS, a long non-coding RNA (lncRNA) that is transcribed in antisense orientation to pre-rRNA. The long non-coding RNA NEAT1 and nuclear paraspeckles are upregulated by the transcription factor HSF1 in the heat shock response" ], "exact_answer": [ [ "Malat1" ], [ "hsr-omega", "hsr\u03c9" ], [ "PAPAS" ], [ "NEAT1" ] ], "type": "list", "id": "5fe31322a43ad3127800004c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The Malat1 long non-coding RNA is upregulated by signalling through the PERK axis of unfolded protein response during flavivirus infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26634309", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 250, "text": "Following the initial discovery of the heat shock RNA omega (hsr\u03c9) gene of Drosophila melanogaster to be non-coding (nc) and also inducible by cell stress, other stress-inducible long non-coding RNAs (lncRNA) have been described in diverse organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22976942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Non-coding RNAs turn up the heat: an emerging layer of novel regulators in the mammalian heat shock response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002685", "endSection": "title" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1031, "text": "It is our hope that much of what is discussed herein may help researchers in integrating the fields of heat shock and ncRNA in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24002685", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 904, "text": "Indeed, as discussed in this review, long noncoding RNAs (lncRNAs), the largest family of noncoding transcripts, have emerged as common regulators of many cellular stressors; including heat shock, metabolic deprivation and DNA damage. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26142536", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 684, "text": "Attenuation of pre-rRNA synthesis in response to heat stress is accompanied by upregulation of PAPAS, a long non-coding RNA (lncRNA) that is transcribed in antisense orientation to pre-rRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27257073", "endSection": "abstract" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1758, "text": "Yet-to-be-explored genomics areas include miRNA, lncRNA, copy number variations, RNA sequencing, and human genome-wide association study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27518140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "LncRNA and mRNA profiling during activation of tilapia macrophages by HSP70", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29228702", "endSection": "title" }, { "offsetInBeginSection": 437, "offsetInEndSection": 570, "text": "56 lncRNA, 10173 mRNA and 1782 transcripts of uncertain coding potential (TUCP) were differentially expressed by pairwise comparison.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29228702", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 920, "text": "LNC_00035 and LNC_000466", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29228702", "endSection": "abstract" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1235, "text": "LNC_000792, LNC_000215, LNC_000035 and LNC_000310, with cis and/or trans relationships with mRNAs, were also involved in ceRNA network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29228702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "The long non-coding RNA NEAT1 and nuclear paraspeckles are upregulated by the transcription factor HSF1 in the heat shock response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30305397", "endSection": "title" }, { "offsetInBeginSection": 247, "offsetInEndSection": 414, "text": "NEAT1 and paraspeckle formation are increased in cells upon exposure to a variety of environmental stressors, and believed to play an important role in cell survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30305397", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 725, "text": "We show that NEAT1 is a novel target gene of heat shock transcription factor 1 (HSF1), and upregulated when the heat shock response pathway is activated by Sulforaphane (SFN) or elevated temperature", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30305397", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1349, "text": "We have found that the expression of HSP70, HSP90, and HSP27 is amplified and sustained during heat shock in NEAT1-depleted cells compared to control cells, indicating that NEAT1 feeds back via an unknown mechanism to regulate HSF1 activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30305397", "endSection": "abstract" } ] }, { "body": "What is the prevalence of poor metabolizers of CYP2C19 among Southern Asians compared to East Asians?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31846723" ], "ideal_answer": [ "Southeast Asians exhibit a higher prevalence of CYP2C19-poor metabolisers compared with Caucasians and East Asians." ], "exact_answer": [ "higher" ], "type": "factoid", "id": "606ad07394d57fd879000050", "snippets": [ { "offsetInBeginSection": 136, "offsetInEndSection": 338, "text": "There is paucity of data on voriconazole therapeutic drug monitoring (TDM) among Southeast Asians, who exhibit a higher prevalence of CYP2C19-poor metabolisers compared with Caucasians and East Asians. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31846723", "endSection": "abstract" } ] }, { "body": "Which R/Bioconductor package has been developed for network-based differential expression analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31179159" ], "ideal_answer": [ "INDEED is an R/Bioconductor package for network based differential expression analysis. INDEED allows users to construct a sparse network based on partial correlation, and to identify biomolecules that have significant changes both at individual expression and pairwise interaction levels." ], "exact_answer": [ "INDEED" ], "type": "factoid", "id": "601d79e01cb411341a000047", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "INDEED: R package for network based differential expression analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31179159", "endSection": "title" }, { "offsetInBeginSection": 538, "offsetInEndSection": 1484, "text": "These interactions are typically evaluated by correlation methods that tend to generate over-complicated networks due to many seemingly indirect associations. In this paper, we introduce a new R/Bioconductor package INDEED that allows users to construct a sparse network based on partial correlation, and to identify biomolecules that have significant changes both at individual expression and pairwise interaction levels. We applied INDEED for analysis of two omic datasets acquired in a cancer biomarker discovery study to help rank disease-associated biomolecules. We believe biomolecules selected by INDEED lead to improved sensitivity and specificity in detecting disease status compared to those selected by conventional statistical methods. Also, INDEED's framework is amenable to further expansion to integrate networks from multi-omic studies, thereby allowing selection of reliable disease-associated biomolecules or disease biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31179159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "INDEED: R package for network based differential expression analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31179159", "endSection": "title" }, { "offsetInBeginSection": 708, "offsetInEndSection": 972, "text": "er, we introduce a new R/Bioconductor package INDEED that allows users to construct a sparse network based on partial correlation, and to identify biomolecules that have significant changes both at individual expression and pairwise interaction levels. We applied ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31179159", "endSection": "abstract" }, { "offsetInBeginSection": 1286, "offsetInEndSection": 1484, "text": "Also, INDEED's framework is amenable to further expansion to integrate networks from multi-omic studies, thereby allowing selection of reliable disease-associated biomolecules or disease biomarkers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31179159", "endSection": "abstract" } ] }, { "body": "Can propofol cause green urine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10999506", "http://www.ncbi.nlm.nih.gov/pubmed/28733841", "http://www.ncbi.nlm.nih.gov/pubmed/27871556", "http://www.ncbi.nlm.nih.gov/pubmed/27900925", "http://www.ncbi.nlm.nih.gov/pubmed/28396792", "http://www.ncbi.nlm.nih.gov/pubmed/25394533", "http://www.ncbi.nlm.nih.gov/pubmed/30809505", "http://www.ncbi.nlm.nih.gov/pubmed/17484185", "http://www.ncbi.nlm.nih.gov/pubmed/21083675", "http://www.ncbi.nlm.nih.gov/pubmed/30625744", "http://www.ncbi.nlm.nih.gov/pubmed/7851359", "http://www.ncbi.nlm.nih.gov/pubmed/23326690", "http://www.ncbi.nlm.nih.gov/pubmed/14738690", "http://www.ncbi.nlm.nih.gov/pubmed/25332856", "http://www.ncbi.nlm.nih.gov/pubmed/26673613", "http://www.ncbi.nlm.nih.gov/pubmed/21623455", "http://www.ncbi.nlm.nih.gov/pubmed/31094132", "http://www.ncbi.nlm.nih.gov/pubmed/28543518" ], "ideal_answer": [ "Yes, propofol can cause green discoloration of urine. It is a rare and benign condition, which occurs when clearance of propofol exceeds the hepatic and extrahepatic elimination." ], "exact_answer": "yes", "type": "yesno", "id": "601c3f041cb411341a000018", "snippets": [ { "offsetInBeginSection": 1082, "offsetInEndSection": 1238, "text": "Reasons for discontinuing propofol are signs of rhabdomyolysis (92.9%), green urine, elevated liver enzymes (71.4% each) and elevated triglycerides (57.1%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28733841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Propofol-Induced Green Urine in a Patient with Refractory Status Epilepticus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30809505", "endSection": "title" }, { "offsetInBeginSection": 208, "offsetInEndSection": 331, "text": "We present the case of a 52-year-old man, who developed green urine following propofol coma therapy for status epilepticus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30809505", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 560, "text": "The green discoloration of urine is a rare and benign condition, which occurs when clearance of propofol exceeds the hepatic and extrahepatic elimination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30809505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Green discolouration of urine following propofol infusion in a dog.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28543518", "endSection": "title" }, { "offsetInBeginSection": 545, "offsetInEndSection": 867, "text": " During mechanical ventilation, anaesthesia was maintained using a propofol target-controlled infusion system and, subsequently, the dog produced bright green urine in the urine collection system. Although previously documented in humans, this appears to be the first report of green urine in a dog following propofol use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28543518", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 219, "text": "Green urine is also caused by medications such as propofol and infections such as pseudomonas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28396792", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 467, "text": "Although it is assumed that the phenolic derivatives of propofol can cause green discoloration of the urine, the actual origin remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27871556", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 323, "text": "An uncommon adverse effect of propofol is green discoloration of the urine, which has been reported not only under general anesthesia but also with sedation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27871556", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 498, "text": "Antibiotics were avoided when propofol was recognized as a rare and benign potential cause of the green urine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10999506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Green Urine Due to Propofol: A Case Report with Review of Literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673613", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 401, "text": "Herein, we present a case of 62-year-old postoperative lady, noticed to be passing green coloured urine believed to be due to intravenous Propofol administration for induction of general anaesthesia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673613", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 351, "text": "Green urine is rare indeed and it is a benign potential side effect of propofol; this phenomenon is related to the metabolism of propofol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30625744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Clinical significance of rare and benign side effects: propofol and green urine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10999506", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Green urine in a patient who received a continuous infusion of propofol: A case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30625744", "endSection": "title" }, { "offsetInBeginSection": 293, "offsetInEndSection": 448, "text": "This phenomenon is due to metabolism of propofol which may lead to a phenolic green chromophore which is conjugated in the liver and excreted in the urine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7851359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Green Urine Discoloration due to Propofol Infusion: A Case Report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326690", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "An analysis of green discoloration of urine caused by propofol infusion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27871556", "endSection": "title" }, { "offsetInBeginSection": 352, "offsetInEndSection": 464, "text": "We experienced green urine from a long-term anesthetized patient who received a continuous infusion of propofol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30625744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "We present a 19-year-old man who excreted green urine after propofol infusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326690", "endSection": "abstract" }, { "offsetInBeginSection": 406, "offsetInEndSection": 559, "text": "green colour of urine due to Propofol occurs when clearance of Propofol exceeds hepatic elimination, and extrahepatic elimination of Propofol occurs. Thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Green urine from propofol infusion is a benign and rare side effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25394533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Grass-green urine from propofol infusion", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25394533", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Propofol-Induced Green Urine in a Patient with Refractory Status Epilepticus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30809505", "endSection": "title" }, { "offsetInBeginSection": 156, "offsetInEndSection": 313, "text": "sedation. An uncommon adverse effect of propofol is green discoloration of the urine, which has been reported not only under general anesthesia but also with", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27871556", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 403, "text": "erein, we present a case of 62-year-old postoperative lady, noticed to be passing green coloured urine believed to be due to intravenous Propofol administration for induction of general anaesthesia. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673613", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 353, "text": "en urine is rare indeed and it is a benign potential side effect of propofol; this phenomenon is related to the metabolism of propofol. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30625744", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 218, "text": "Green urine is also caused by medications such as propofol and infections such as pseudomonas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28396792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Green Urine Due to Propofol: A Case Report with Review of Literature", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673613", "endSection": "title" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1012, "text": "LUSION: We experienced a case of a patient with green discoloration of the urine after general anesthesia using propofol. Al", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27871556", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 291, "text": "After starting continuous infusion of propofol for postoperative sedation, his urine became dark green.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326690", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 541, "text": "We believe that the green discoloration of the urine was caused by propofol infusion and was related to impaired enterohepatic circulation and extrahepatic glucuronidation in the kidneys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23326690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "WHAT IS KNOWN AND OBJECTIVE: Propofol, a commonly used sedative, has on rare occasions, been reported to discolour urine green", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21083675", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 664, "text": " IS NEW AND CONCLUSION: Green discoloration of the urine from propofol infusion is dose dependent. It", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21083675", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 366, "text": " We report on a patient who produced dark green discoloration of urine from prolonged propofol infusion, administered for intractable epilepsy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21083675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Dark green discoloration of the urine after prolonged propofol infusion: a case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21083675", "endSection": "title" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1011, "text": " experienced a case of a patient with green discoloration of the urine after general anesthesia using propofol. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27871556", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 167, "text": "On the third day of propofol infusion his urine was dark green.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10999506", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Green urine from propofol infusion is a benign and rare side effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25394533", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 555, "text": "The green colour of urine due to Propofol occurs when clearance of Propofol exceeds hepatic elimination, and extrahepatic elimination of Propofol occurs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26673613", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 422, "text": "ur change is dose dependent. We report on a patient who produced dark green discoloration of urine from prolonged propofol infusion, administered for intractable epilepsy.CASE SUMMARY: The colour intensity of the patient's uri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21083675", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 335, "text": "Several substances in literature have been associated with green urine including propofol, biliverdin, metoclopramide, methylene blue, indigo blue, amitriptyline, methocarbamol, indomethacin, promethazine, cimetidine and food colourings. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31094132", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 323, "text": "We discuss a case of a benign cause of green discoloration of urine caused by propofol infusion, which reversed following its discontinuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623455", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 469, "text": "The patient's urine subsequently showed a green discoloration. Urine discoloration was completely reversible upon discontinuation of propofol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332856", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 274, "text": "Two days after admittance, we observed a green discoloration of the urine. This is a rare and benign side effect of propofol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27900925", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "We describe a 58-year-old man who developed green urine after operation on a pressure ulcer. The discolouration disappeared gradually after two days. We think that the use of methylene blue dye during the revision of the wounds and the use of the sedative propofol could have caused it.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17484185", "endSection": "abstract" } ] }, { "body": "Are Gram positive bacteria able to release extracellular vesicles?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31988111", "http://www.ncbi.nlm.nih.gov/pubmed/31675472", "http://www.ncbi.nlm.nih.gov/pubmed/31776460" ], "ideal_answer": [ "Yes, Gram-negative and Gram-positive bacteria release a variety of membrane vesicles through different formation routes." ], "exact_answer": "yes", "type": "yesno", "id": "6032187e1cb411341a000132", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Gram-negative and Gram-positive bacteria release a variety of membrane vesicles through different formation routes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Release of extracellular vesicles (EVs) is a common feature among eukaryotes, archaea, and bacteria. However, the biogenesis and downstream biological effects of EVs released from gram-positive bacteria remain poorly characterized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31988111", "endSection": "abstract" }, { "offsetInBeginSection": 1485, "offsetInEndSection": 1597, "text": " Our findings provide new insight into the role of EVs from gram-positive oral bacteria in periodontal diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31675472", "endSection": "abstract" } ] }, { "body": "Describe a cytokine release syndrome.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32776808", "http://www.ncbi.nlm.nih.gov/pubmed/32166291", "http://www.ncbi.nlm.nih.gov/pubmed/33262810", "http://www.ncbi.nlm.nih.gov/pubmed/18382853", "http://www.ncbi.nlm.nih.gov/pubmed/32474885", "http://www.ncbi.nlm.nih.gov/pubmed/32983172", "http://www.ncbi.nlm.nih.gov/pubmed/32446778", "http://www.ncbi.nlm.nih.gov/pubmed/17471824", "http://www.ncbi.nlm.nih.gov/pubmed/31755797", "http://www.ncbi.nlm.nih.gov/pubmed/32678378" ], "ideal_answer": [ "The major factor responsible for acute respiratory distress syndrome is the so-called \"cytokine storm,\" which is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines.", "Cytokine release syndrome is defined by the release of cytokines from sarcoplasmic reticulum (SR) and is associated with retinal vein occlusions, fatigue and dyspnea.", "Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction that is associated with chimeric antigen receptor (CAR)-T cell therapy, therapeutic antibodies, and haploidentical allogeneic transplantation.", "cytokine storm is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines.", "Cytokine release syndrome is characterized by the release of cytokines from the cytosol into the cerebrospinal fluid (CSF) and cytokine production from the sarcoplasmic reticulum (SR).", "the so-called \"cytokine storm,\" which is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines.", "\"Cytokine storm,\" is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines. I", "A severe immune response in patients with coronavirus disease 2019 (COVID-19) can cause a potentially lethal unconstrained inflammatory cytokine storm, known as cytokine release syndrome (CRS)." ], "type": "summary", "id": "6032722f1cb411341a00013d", "snippets": [ { "offsetInBeginSection": 434, "offsetInEndSection": 674, "text": "The major factor responsible for acute respiratory distress syndrome is the so-called \"cytokine storm,\" which is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32983172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "A severe immune response in patients with coronavirus disease 2019 (COVID-19) can cause a potentially lethal unconstrained inflammatory cytokine storm, known as cytokine release syndrome (CRS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33262810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 546, "text": "Immune cells secrete small protein molecules that aim for cell-cell communications. These small molecules are called cytokines. Targeting cancer cells with administration of bispecific antibodies and natural extracts results in elevated circulating levels of inflammatory cytokines, including interferon-\u03b3 and interleukin (IL)-6, which lead to cell toxicity. Sustained release of cytokines due to immunotherapy or hormonal issues causes various diseases. Novel T cell-engaging therapies and monoclonal antibodies cause cytokine release syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31755797", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 377, "text": "hile immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute\u00a0respiratory distress syndrome, may also occur in some patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32474885", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 912, "text": "Available evidence indicate that the so called \"cytokine storm\" an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32446778", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 465, "text": "ts: A 14-year-old boy with refractory B cell precursor acute lymphoblastic leukemia given chimeric antigen receptor cells developed severe cytokine release syndrome 7 days after the drug product infusion with progressive respiratory failure. He wa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32166291", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 900, "text": "heless, CAR-T cell treatment is associated with toxicities such as cytokine release syndrome, which can range in severity from mild flu-like symptoms to life-threatening vasodilatory shock, and a neurological syndrome termed ICANS (immune effector cell-associated neurotoxicity syndrome), which can also range in severity from a temporary cognitive deficit lasting only a few hours to lethal cerebral edema. In this revi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32776808", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Acute cytokine release syndromes are associated with some therapeutic antibodies in man, leading to a spectrum of clinical signs from nausea, chills and fever to more serious dose limiting hypotension and tachycardia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18382853", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 680, "text": "However, some patients may experience severe, life-threatening reactions that result from massive release of cytokines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17471824", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 472, "text": "When cytokines are released into the circulation, systemic symptoms such as fever, nausea, chills, hypotension, tachycardia, asthenia, headache, rash, scratchy throat, and dyspnea can result.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17471824", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Cytokine release syndrome is a systemic inflammatory condition that may occur after treatment with some types of immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32678378", "endSection": "abstract" } ] }, { "body": "Which genes are the main markers of primitive Endoderm (prEN) formation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7772748", "http://www.ncbi.nlm.nih.gov/pubmed/27060901", "http://www.ncbi.nlm.nih.gov/pubmed/1455234", "http://www.ncbi.nlm.nih.gov/pubmed/22172669", "http://www.ncbi.nlm.nih.gov/pubmed/23193166", "http://www.ncbi.nlm.nih.gov/pubmed/24835466", "http://www.ncbi.nlm.nih.gov/pubmed/18725515", "http://www.ncbi.nlm.nih.gov/pubmed/22608553", "http://www.ncbi.nlm.nih.gov/pubmed/18816845", "http://www.ncbi.nlm.nih.gov/pubmed/24504341", "http://www.ncbi.nlm.nih.gov/pubmed/22607194", "http://www.ncbi.nlm.nih.gov/pubmed/18083160", "http://www.ncbi.nlm.nih.gov/pubmed/22914948", "http://www.ncbi.nlm.nih.gov/pubmed/20925113", "http://www.ncbi.nlm.nih.gov/pubmed/9895328", "http://www.ncbi.nlm.nih.gov/pubmed/24752320" ], "ideal_answer": [ "The genes involved in primitive endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, p dgfr\u03b1, gATA6, nanog, pDgfralpha, egam1 and dab2.", "Fgf receptor/Erk signalling is known to be required for specification of the primitive endoderm. Platelet derived growth factor receptor alpha (Pdgfr\u03b1) as an early-expressed protein that is also a marker of the later primitive endoderm lineage. ES cells expressing exogenous EGAM1 preferentially differentiate into extra-embryonic primitive endoderm. Lrp2 is a novel PrE precursor (pre-PrE) marker by using a microarray strategy that combines a transcriptome analysis of three stem cell lines and early embryos.", "The genes which are the main markers of primitive Endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, pDgfr\u03b1, gATA6, nanog, p dgfralpha, egam1 and dab2.", "The main markers of primitive Endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, p dgfr\u03b1, gATA6, nanog, pDgfralpha, egam1 and dab2.", "The main markers of primitive Endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, pDgfr\u03b1, gATA6, nanog, p dgfralpha, egam1 and dab2.", "The markers of primitive endoderm (prEN) formation are the transcriptional activators fgf4 and its ligand, lrp2, gata4, pdgfra, p dgfr\u03b1, gATA6, nanog, pDgfralpha, egam1 and dab2." ], "exact_answer": [ [ "FGF4" ], [ "GATA4" ], [ "GATA6" ], [ "PDGFRA" ], [ "EGAM1" ], [ "LRP2" ] ], "type": "list", "id": "5fdb4190a43ad3127800001b", "snippets": [ { "offsetInBeginSection": 992, "offsetInEndSection": 1127, "text": "This inhibitor caused a loss of expression of markers of primitive endoderm cell fate and maintenance of the pluripotency marker Nanog.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24752320", "endSection": "abstract" }, { "offsetInBeginSection": 1115, "offsetInEndSection": 1244, "text": "Thus, Fgf4 mutant embryos initiated the PrE program but exhibited defects in its restriction phase, when lineage bias is acquired", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193166", "endSection": "abstract" }, { "offsetInBeginSection": 671, "offsetInEndSection": 766, "text": "Fgf receptor/Erk signalling is known to be required for specification of the primitive endoderm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24752320", "endSection": "abstract" }, { "offsetInBeginSection": 552, "offsetInEndSection": 813, "text": "gf4 heterozygous blastocysts exhibited increased numbers of NANOG-positive EPI cells and reduced numbers of GATA6-positive PrE cells, suggesting that FGF signaling is tightly regulated to ensure specification of the appropriate numbers of cells for each lineage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193166", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 443, "text": "Recently, the identification of platelet derived growth factor receptor alpha (Pdgfr\u03b1) as an early-expressed protein that is also a marker of the later primitive endoderm lineage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22914948", "endSection": "abstract" }, { "offsetInBeginSection": 1159, "offsetInEndSection": 1419, "text": "Taken together, the results obtained in this study suggested that mouse ES cells expressing exogenous EGAM1 preferentially differentiate into extra-embryonic primitive endoderm lineages, rather than embryonic lineages or extra-embryonic trophectoderm lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22608553", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 583, "text": " In this work, we isolated Lrp2 as a novel PrE precursor (pre-PrE) marker by using a microarray strategy that combines a transcriptome analysis of three stem cell lines and early embryos", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18083160", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 747, "text": "We have identified platelet-derived growth factor receptor alpha (Pdgfralpha) as an early-expressed protein that is also a marker of the later PrE lineage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18725515", "endSection": "abstract" }, { "offsetInBeginSection": 774, "offsetInEndSection": 948, "text": "Furthermore, the subcellular location of Lrp2, Disabled-2 (Dab2) and Collagen-IV shows that the epithelial structure is acquired in individual cells through successive steps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18083160", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1141, "text": "More specifically, overexpression of Gata6 or Foxa2 alone induced molecular and morphological markers of primitive endoderm, which occurred concomitantly with the upregulation of the Wnt6 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22607194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Gene knockouts in mice have showed that Grb2 and GATA6 are essential for the formation of primitive endoderm in blastocysts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20925113", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1213, "text": "Thus, the current study establishes that GATA6 is essential for the formation of primitive endoderm, at a much earlier stage then previously recognized, and expression of GATA6 discriminates parietal endoderm from visceral endoderm lineages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18816845", "endSection": "abstract" }, { "offsetInBeginSection": 549, "offsetInEndSection": 730, "text": "At embryonic day (E) 5.0, parietal endoderm cells continue to express both GATA4 and GATA6; however, visceral endoderm cells express GATA4 but exhibit a reduced expression of GATA6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18816845", "endSection": "abstract" }, { "offsetInBeginSection": 731, "offsetInEndSection": 798, "text": "By and after E5.5, visceral endoderm cells no longer express GATA6.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18816845", "endSection": "abstract" }, { "offsetInBeginSection": 377, "offsetInEndSection": 474, "text": "We further analyzed the dynamic expression and mutant phenotypes of GATA6 in early mouse embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18816845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Cells of the inner cell mass (ICM) of the mouse blastocyst differentiate into the pluripotent epiblast or the primitive endoderm (PrE), marked by the transcription factors NANOG and GATA6, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24835466", "endSection": "abstract" }, { "offsetInBeginSection": 792, "offsetInEndSection": 951, "text": "Moreover, we found that subsequent expression of Sox17 and Gata4--later markers of the PrE--depends on the presence of Fgf4 produced by Nanog-expressing cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22172669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Ectopic expression of GATA6 bypasses requirement for Grb2 in primitive endoderm formation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20925113", "endSection": "title" }, { "offsetInBeginSection": 916, "offsetInEndSection": 1160, "text": "Moreover, the expression of an epiblast marker gene, NANOG, and a primitive endoderm marker gene, GATA6, remained unchanged, whereas the expression of another primitive endoderm marker gene, HNF4A, was significantly reduced in FGFR2-KD embryos.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27060901", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1242, "text": "Sox17, a marker of primitive endoderm, is not detected following prolonged culture of such embryos, but can be rescued by provision of exogenous FGF4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24504341", "endSection": "abstract" } ] }, { "body": "What are the EMA and FDA recommendations regarding pharmacogenetic testing for abacavir?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23204921" ], "ideal_answer": [ "Abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir. Accordingly to these results the abacavir label has been modified: the European Medicines Agency (EMA) and the FDA recommend/suggested that the administration of abacavir must be preceded by a specific genotyping test. The HLA locus is extremely polymorphic, exhibiting many closely related alleles, making it difficult to discriminate HLA-B*57:01 from other related alleles, and a number of different molecular techniques have been developed recently to detect the presence of HLA-B*57:01." ], "type": "summary", "id": "606ae55d94d57fd879000057", "snippets": [ { "offsetInBeginSection": 268, "offsetInEndSection": 999, "text": "Pharmacogenetic studies have revealed that abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir. Accordingly to these results the abacavir label has been modified: the European Medicines Agency (EMA) and the FDA recommend/suggested that the administration of abacavir must be preceded by a specific genotyping test. The HLA locus is extremely polymorphic, exhibiting many closely related alleles, making it difficult to discriminate HLA-B*57:01 from other related alleles, and a number of different molecular techniques have been developed recently\u00a0to detect the presence of HLA-B*57:01. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204921", "endSection": "abstract" } ] }, { "body": "Describe PWMScan", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29514181" ], "ideal_answer": [ "PWMScan is used to scan a position weight matrix (PWM) against a genome or, in general, a large set of DNA sequences. The PWM is the most commonly used mathematical model to describe the DNA binding specificity of a transcription factor (TF). ", "PWMScan is a fast web-based tool to scan server- resident genomes for matches to a user-suppressor PWM or transcription factor binding site model from a public database.", "pwmscan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied pwm or transcription factor binding site model from a public database.", "PWMScan is a fast web-based tool to scan server- resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "pwmscan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied pw or transcription factor binding site model from a public database.", "PWMScan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database. It is available for pre-assembled copies of the original PWM/TF binding model.", "Transcription factors regulate gene expression by binding to specific short DNA sequences of 5-20 bp to regulate the rate of transcription of genetic information from DNA to messenger RNA. PWMScan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "PWMScan is a fast web-based tool to scan server- resident genomes for matches to a user-suppressor PWM or transcription factor binding site model from a Public database.", "PWMScan is a fast web-based tool for scanning entire genomes with a position-specific weight matrix. It's a fast and cheap way to scan a large portion of an entire genome with a small amount of time." ], "type": "summary", "id": "60291a0c1cb411341a00010d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "PWMScan: a fast tool for scanning entire genomes with a position-specific weight matrix.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 373, "text": "Transcription factors regulate gene expression by binding to specific short DNA sequences of 5-20 bp to regulate the rate of transcription of genetic information from DNA to messenger RNA. We present PWMScan, a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514181", "endSection": "abstract" } ] }, { "body": "Is vocimagene amiretrorepvec effective for glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32816892", "http://www.ncbi.nlm.nih.gov/pubmed/33119048" ], "ideal_answer": [ "No. Treatment with vocimagene amiretrorepvec did not improve survival of glioblastoma patients." ], "exact_answer": "no", "type": "yesno", "id": "6025d88c1cb411341a0000b6", "snippets": [ { "offsetInBeginSection": 1418, "offsetInEndSection": 1618, "text": "CONCLUSIONS: These results support an immune-related mechanism of action for Toca 511 and Toca FC, and suggest that molecular and immunologic signatures are related to clinical benefit from treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32816892", "endSection": "abstract" }, { "offsetInBeginSection": 1845, "offsetInEndSection": 2434, "text": "The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P\u2009=\u2009.62). The secondary end points did not demonstrate statistically significant differences. The rates of adverse events were similar in the Toca 511/FC group and the SOC control group.Conclusions and Relevance: Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33119048", "endSection": "abstract" } ] }, { "body": "List the major royal jelly proteins in Apis mellifera.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22571915", "http://www.ncbi.nlm.nih.gov/pubmed/24279675", "http://www.ncbi.nlm.nih.gov/pubmed/32042077", "http://www.ncbi.nlm.nih.gov/pubmed/31410279" ], "ideal_answer": [ "The genome of the western honeybee (Apis mellifera) harbors nine transcribed major royal jelly protein genes (mrjp1-9) which originate from a single-copy precursor via gene duplication." ], "exact_answer": [ [ "MRJP1" ], [ "MRJP2" ], [ "MRJP3" ], [ "MRJP4" ], [ "MRJP5" ], [ "MRJP6" ], [ "MRJP7" ], [ "MRJP8" ], [ "MRJP9" ] ], "type": "list", "id": "605700d294d57fd879000021", "snippets": [ { "offsetInBeginSection": 586, "offsetInEndSection": 725, "text": "The exposure of nurse bees to pesticides reduced the expression of four of the major royal jelly proteins (MRJP1, MRJP2, MRJP4, and MRJP5) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32042077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "The genome of the western honeybee (Apis mellifera) harbors nine transcribed major royal jelly protein genes (mrjp1-9) which originate from a single-copy precursor via gene duplication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31410279", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 378, "text": " The protein moiety of royal jelly comprises mostly major royal jelly proteins (MRJPs) of which the coding genes (mrjp1-9) have been identified on chromosome 11 in the honeybee's genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24279675", "endSection": "abstract" }, { "offsetInBeginSection": 864, "offsetInEndSection": 925, "text": "five belonged to the family of major royal jelly proteins 1-5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22571915", "endSection": "abstract" } ] }, { "body": "What is BEL(Biological Expression Language) used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23515068", "http://www.ncbi.nlm.nih.gov/pubmed/29048466", "http://www.ncbi.nlm.nih.gov/pubmed/27694210", "http://www.ncbi.nlm.nih.gov/pubmed/31603193", "http://www.ncbi.nlm.nih.gov/pubmed/27554092", "http://www.ncbi.nlm.nih.gov/pubmed/30624649", "http://www.ncbi.nlm.nih.gov/pubmed/27173525", "http://www.ncbi.nlm.nih.gov/pubmed/27402677", "http://www.ncbi.nlm.nih.gov/pubmed/27173520", "http://www.ncbi.nlm.nih.gov/pubmed/30961584", "http://www.ncbi.nlm.nih.gov/pubmed/26636108", "http://www.ncbi.nlm.nih.gov/pubmed/26200752" ], "ideal_answer": [ "Biological Expression Language (BEL) is a novel method for the statistical extraction of causal relation relationships from large biomedical literature datasets.", "Biological expression language (BEL) is a syntax representation allowing for the structured representation of a broad range of biological relationships.", "Biological expression language (BEL) is a syntax representation allowing for the structured representation of a broad range of biological relationships. It is used in various situations to extract such knowledge and transform it into BEL networks.", "Biological Expression Language (BEL) is a novel method for the automatic extraction of causal relation networks from biomedical literature.", "Biological Expression Language (BEL) is a novel method for statistical extraction of causal relation networks from biomedical literature.", "Biological Expression Language (BEL) is a literature-based method for the statistical estimation of causal relation relationships among entities (e.g. species, populations, populations) and temporal relationships among them." ], "type": "summary", "id": "604bc5b41cb411341a000173", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "The BioCreative-V community proposed a challenging task of automatic extraction of causal relation network in Biological Expression Language (BEL) from the biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30624649", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 373, "text": " The BioCreative community has organized a shared task to evaluate the robustness of the causal relationship extraction algorithms in Biological Expression Language (BEL) from biomedical literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30961584", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 575, "text": "Biological expression language (BEL) is a syntax representation allowing for the structured representation of a broad range of biological relationships. It is used in various situations to extract such knowledge and transform it into BEL networks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31603193", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 134, "text": "Biological Expression Language (BEL) assembles knowledge networks from biological relations across multiple modes and scales.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29048466", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 307, "text": "or network representation, the Biological Expression Language (BEL) is well designed to collate findings from the scientific literature into biological network models. To", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27694210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Biological expression language (BEL) is one of the most popular languages to represent the causal and correlative relationships among biological events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27173520", "endSection": "abstract" }, { "offsetInBeginSection": 561, "offsetInEndSection": 777, "text": "his work, we demonstrate how disease-related epigenetic knowledge can be systematically captured and integrated with heterogeneous information into a functional context using Biological Expression Language (BEL). Thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26636108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Summary: Biological Expression Language (BEL) assembles knowledge networks from biological relations across multiple modes and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29048466", "endSection": "abstract" }, { "offsetInBeginSection": 860, "offsetInEndSection": 1052, "text": "e-edge relationships are described using the Biological Expression Language (BEL), which allows for the semantic representation of life science relationships in a computable format. The Networ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23515068", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Biological expression language (BEL) is one of the main formal representation models of biological networks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27173525", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 483, "text": "logical expression language (BEL) is a syntax representation allowing for the structured representation of a broad range of biological relationships. It ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31603193", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 568, "text": "semi-automated knowledge extraction workflow is presented that was developed to allow users to extract causal and correlative relationships from scientific literature and to transcribe them into the computable and human readable Biological Expression Language (BEL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26200752", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 479, "text": "Biological expression language (BEL) is a syntax representation allowing for the structured representation of a broad range of biological relationships.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31603193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "The extraction of complex relationships and their conversion to biological expression language (BEL) overview of the BioCreative VI (2017) BEL track.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31603193", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Biological expression language (BEL) is one of the most popular languages to represent the causal and correlative relationships among biological events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27173520", "endSection": "abstract" }, { "offsetInBeginSection": 136, "offsetInEndSection": 304, "text": "For network representation, the Biological Expression Language (BEL) is well designed to collate findings from the scientific literature into biological network models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27694210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Biological expression language (BEL) is one of the main formal representation models of biological networks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27173525", "endSection": "abstract" }, { "offsetInBeginSection": 353, "offsetInEndSection": 506, "text": "BEL was designed to capture relationships not only between proteins or chemicals, but also complex events such as biological processes or disease states.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27554092", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 480, "text": "BEL is an advanced knowledge representation format which has been designed to be both human readable and machine processable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27402677", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 352, "text": "Here, we describe the new corpora in the systems biology modeling language BEL for training and testing biological relationship extraction systems that we prepared for the BioCreative V BEL track.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27554092", "endSection": "abstract" } ] }, { "body": "Which database contains gene expression data for yeast?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25024351", "http://www.ncbi.nlm.nih.gov/pubmed/10779484", "http://www.ncbi.nlm.nih.gov/pubmed/20025988", "http://www.ncbi.nlm.nih.gov/pubmed/25404128", "http://www.ncbi.nlm.nih.gov/pubmed/24350770" ], "ideal_answer": [ "We developed the ExpressDB database for yeast RNA expression data and loaded it with approximately 17.5 million pieces of data reported by 11 studies with three different kinds of high-throughput RNA assays.", "The MOPED database (http://arep.med.har. Edu/ expressDB) provides access to extensive gene expression data from yeast genomes.", "We developed the ExpressDB database for yeast RNA expression data and loaded it with approximately 17.5 million pieces of data reported by 11 studies with three different kinds of high-throughput RNA assays. MOPED (Multi-Omics Profiling Expression Database; http://moped.proteinspire.org) has transitioned from solely a protein expression database to a multi-omics resource for human and model organisms.", "The ExpressDB database is a database for yeast RNA expression data. The FED database is for fungal gene expression data for yeast." ], "exact_answer": [ "ExpressDB" ], "type": "factoid", "id": "5fe30efea43ad31278000038", "snippets": [ { "offsetInBeginSection": 109, "offsetInEndSection": 316, "text": "We developed the ExpressDB database for yeast RNA expression data and loaded it with approximately 17.5 million pieces of data reported by 11 studies with three different kinds of high-throughput RNA assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10779484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "MOPED (Multi-Omics Profiling Expression Database; http://moped.proteinspire.org) has transitioned from solely a protein expression database to a multi-omics resource for human and model organisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404128", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "MOPED enables discoveries through consistently processed proteomics data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24350770", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The Model Organism Protein Expression Database (MOPED, http://moped.proteinspire.org) is an expanding proteomics resource to enable biological and biomedical discoveries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24350770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": "yStreX: yeast stress expression database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25024351", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "The filamentous fungal gene expression database (FFGED).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20025988", "endSection": "title" }, { "offsetInBeginSection": 120, "offsetInEndSection": 319, "text": "To aid research on fungal gene expression, we constructed a novel, comprehensive, free database, the filamentous fungal gene expression database (FFGED), available at http://bioinfo.townsend.yale.edu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20025988", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 318, "text": "developed the ExpressDB database for yeast RNA expression data and loaded it with approximately 17.5 million pieces of data reported by 11 studies with three different kinds of high-throughput RNA assays. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10779484", "endSection": "abstract" } ] }, { "body": "Which CYP gene polymorphism is a well-known predictor of efavirenz disposition?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31514420", "http://www.ncbi.nlm.nih.gov/pubmed/31628422" ], "ideal_answer": [ "Cytochrome P450 (CYP) CYP2B6 G516T (rs3745274) is a well-known predictor of efavirenz disposition." ], "exact_answer": [ "CYP2B6 G516T", "rs3745274" ], "type": "factoid", "id": "606b5ba794d57fd879000067", "snippets": [ { "offsetInBeginSection": 125, "offsetInEndSection": 223, "text": "Cytochrome P450 (CYP) CYP2B6 G516T (rs3745274) is a well-known predictor of efavirenz disposition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31628422", "endSection": "abstract" } ] }, { "body": "What is the role of the IRE1a-XBP1 pathway?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30355343" ], "ideal_answer": [ "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response, playing an important role in the regulation of cell differentiation.", "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response, playing an important role in the regulation of cell proliferation and differentiation.", "The inositol-requiring enzyme 1a (IRE1a)/X-box binding protein 1 (XBP1) pathway plays crucial roles in cell survival and cell death by upregulating UPR-associated genes involved in protein entry into the endoplasmic reticulum and ER-associated degradation (ERAD).", "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfold protein response.", "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response. The pathway is indispensable for the development of secretory cells by facilitating protein folding and enhancing secretory capacity.", "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response.", "Genome-wide analyses reveal the IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation.", "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response. It is indispensable for the development of secretory cells by facilitating protein folding and enhancing secretory capacity." ], "exact_answer": [ "Promotion of T helper cell differentiation by resolving secretory stress and accelerating proliferation" ], "type": "factoid", "id": "605cc21d94d57fd879000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Genome-wide analyses reveal the IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30355343", "endSection": "title" }, { "offsetInBeginSection": 1977, "offsetInEndSection": 2352, "text": "We confirm and detail the critical role of the IRE1a-XBP1 pathway during Th2 lymphocyte activation in regulating cytokine expression, secretion, and cell proliferation. Our high-quality genome-wide XBP1 ChIP and gene expression data provide a rich resource for investigating XBP1-regulated genes. We provide a browsable online database available at http://data.teichlab.org .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30355343", "endSection": "abstract" } ] }, { "body": "Can Panitumumab cause trichomegaly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20726623", "http://www.ncbi.nlm.nih.gov/pubmed/23010833", "http://www.ncbi.nlm.nih.gov/pubmed/33028137" ], "ideal_answer": [ "Yes. Panitumumab is EGFR inhibitor that is associated with eyelash trichomegaly." ], "exact_answer": "yes", "type": "yesno", "id": "601cb7a61cb411341a000026", "snippets": [ { "offsetInBeginSection": 2318, "offsetInEndSection": 2451, "text": "Xerosis was present in two cases, and paronychia, pyogenic granuloma, trichomegaly, and madarosis were observed in one patient each. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33028137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 444, "text": "Eyelash trichomegaly is an uncommon drug-associated sequelae experienced during treatment with epidermal growth factor receptor (EGFR) inhibitors. Elongation of the eyelashes induced by these agents has predominantly been observed in oncology patients with either colorectal or lung cancer. It is most frequently associated with cetuximab and erlotinib; however, it has also been described in individuals treated with gefitinib or panitumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20726623", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Trichomegaly of the eyelashes during therapy with epidermal growth factor receptor inhibitors: report of 3 cases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23010833", "endSection": "title" }, { "offsetInBeginSection": 232, "offsetInEndSection": 375, "text": "Trichomegaly of the eyelashes is a rare adverse effect of EGFR inhibitor therapy and is characterized by a paradoxical overgrowth of eyelashes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23010833", "endSection": "abstract" } ] }, { "body": "List proteins that are contained in atherosclerotic plaques?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32012358", "http://www.ncbi.nlm.nih.gov/pubmed/31382484", "http://www.ncbi.nlm.nih.gov/pubmed/29907817", "http://www.ncbi.nlm.nih.gov/pubmed/29129081" ], "ideal_answer": [ "extracellular matrix proteins\nbiglycan\nLumican\nApolipoprotein A-I" ], "exact_answer": [ [ "extracellular matrix proteins" ], [ "biglycan" ], [ "Lumican" ], [ "Apolipoprotein A-I" ] ], "type": "list", "id": "6082d9044e6a4cf63000000c", "snippets": [ { "offsetInBeginSection": 253, "offsetInEndSection": 311, "text": "d extracellular matrix (ECM) proteins in the arterial wall", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32012358", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 108, "text": "apolipoprotein A-I (apoA-I)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31382484", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1222, "text": "Among the proteins with increased abundance were prominent extracellular matrix proteins such as biglycan and lumican, whereas cytoskeletal markers for contractile smooth muscle cells (SMCs) were decreased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29129081", "endSection": "abstract" }, { "offsetInBeginSection": 927, "offsetInEndSection": 986, "text": ", a biomarker panel of FBLN1C, APOE and CDH13 was identifie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29907817", "endSection": "abstract" } ] }, { "body": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32705489", "http://www.ncbi.nlm.nih.gov/pubmed/32899411", "http://www.ncbi.nlm.nih.gov/pubmed/33236786", "http://www.ncbi.nlm.nih.gov/pubmed/32427099", "http://www.ncbi.nlm.nih.gov/pubmed/32201576", "http://www.ncbi.nlm.nih.gov/pubmed/30166628", "http://www.ncbi.nlm.nih.gov/pubmed/31468518", "http://www.ncbi.nlm.nih.gov/pubmed/30656450", "http://www.ncbi.nlm.nih.gov/pubmed/30343943", "http://www.ncbi.nlm.nih.gov/pubmed/29090338", "http://www.ncbi.nlm.nih.gov/pubmed/31064215", "http://www.ncbi.nlm.nih.gov/pubmed/30255934", "http://www.ncbi.nlm.nih.gov/pubmed/29100083", "http://www.ncbi.nlm.nih.gov/pubmed/31926053", "http://www.ncbi.nlm.nih.gov/pubmed/32139178" ], "ideal_answer": [ "yes, developmental and epileptic encephalopathies (dees) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis.", "Clinical characteristics of Developmental and Epileptic Encephalopathies include global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression.", "Clinical characteristics of Developmental and Epileptic Encephalopathies (DEEs) include global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression.", "Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe epilepsies characterized by early-onset, refractory seizures occurring in the context of developmental regression or plateauing, resulting in deterioration in developmental, cognitive, and motor functions.", "developmental and epileptic encephalopathies (dees) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis.", "Developmental and epileptic encephalopathies (DEEs) are a group of severe neurological disorders characterized by global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression.", "Developmental and epileptic encephalopathies (DEEs) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis.", "SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both.", " Developmental epileptic encephalopathies (DEEs) are genetically heterogeneous severe childhood-onset epilepsies with developmental delay or cognitive deficits.", "Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression.", "Clinical characteristics of Developmental and Epileptic Encephalopathies (DEEs) include global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression, intellectual disability, and brain anomalies.", "Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that have poor prognosis. DEEs are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression." ], "exact_answer": [ [ "refractory seizures" ], [ "developmental delay" ], [ "poor prognosis" ], [ "deterioration in motor functions" ], [ "abundant epileptiform activity" ], [ "regression associated with ongoing epileptic activity" ], [ "genetically heterogeneous severe childhood-onset epilepsies with developmental delay or cognitive deficits" ], [ "cognitive deficits" ], [ "facial dysmorphim" ], [ "macrocephaly" ], [ "cerebellar dysgenesis" ] ], "type": "list", "id": "604b8cf71cb411341a000171", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Developmental and epileptic encephalopathies (DEEs) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32201576", "endSection": "abstract" }, { "offsetInBeginSection": 5, "offsetInEndSection": 201, "text": "Developmental and epileptic encephalopathies (DEEs) are a group of devastating disorders caused by epileptic activity, resulting in deterioration in developmental, cognitive, and motor functions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32705489", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 145, "text": "SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236786", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 215, "text": "Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30166628", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 171, "text": " Developmental epileptic encephalopathies (DEEs) are genetically heterogeneous severe childhood-onset epilepsies with developmental delay or cognitive deficits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31468518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30343943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe epilepsies characterized by early-onset, refractory seizures occurring in the context of developmental regression or plateauing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32899411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "AIM: Developmental and epileptic encephalopathies (DEEs) are a group of devastating disorders caused by epileptic activity, resulting in deterioration in developmental, cognitive, and motor functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32705489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "Developmental and epileptic encephalopathies (DEEs) are genetically heterogenous conditions, often characterized by early onset, EEG interictal epileptiform abnormalities, polymorphous and drug-resistant seizures, and neurodevelopmental impairments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30656450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "PURPOSE: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30166628", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "OBJECTIVE: SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30343943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Developmental and epileptic encephalopathies (DEEs) are genetically heterogenous conditions, often characterized by early onset, EEG interictal epileptiform abnormalities, polymorphous and drug-resistant seizures, and neurodevelopmental impairments. In t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30656450", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 512, "text": "ental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on electroencephalogram (EEG), and developmental impairment or regression. CACNA1E is ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31064215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Developmental and epileptic encephalopathies (DEEs) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis. DEE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32201576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe epilepsies characterized by early-onset, refractory seizures occurring in the context of developmental regression or plateauing. E", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32899411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30343943", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29100083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Developmental and Epileptic encephalopathies (DEE) describe heterogeneous epilepsy syndromes, characterized by early-onset, refractory seizures and developmental delay (DD). Se", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31926053", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 400, "text": "Early infantile epileptic encephalopathy (EIEE) is one of the earliest forms of DEE, manifesting as frequent epileptic spasms and characteristic electroencephalogram findings in early infancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32899411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "PURPOSE: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30166628", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 220, "text": "Early-onset developmental and epileptic encephalopathy (DEE) is characterized by repeated seizures beginning within 3\u00a0months of birth and severe interictal epileptiform discharge, including burst suppression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32139178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "OBJECTIVES: Developmental encephalopathic epilepsies (DEEs) are characterized by refractory seizures, disability, and ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30255934", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Developmental and Epileptic encephalopathies (DEE) describe heterogeneous epilepsy syndromes, characterized by early-onset, refractory seizures and developmental delay (DD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31926053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29090338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of disorders characterized by epilepsy with comorbid intellectual disability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32427099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "AIM: Developmental and epileptic encephalopathies (DEEs) are a group of devastating disorders caused by epileptic activity, resulting in deterioration in developmental, cognitive, and motor funct", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32705489", "endSection": "abstract" } ] }, { "body": "Which methods exist for efficient calculation of Elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32348455", "http://www.ncbi.nlm.nih.gov/pubmed/25380956" ], "ideal_answer": [ "EFM-Ta is a novel algorithm that uses a linear programming-based tree search and efficiently enumerates a subset of EFMs in genome-scale metabolic networks (GSMNs). The stand-alone software TreeEFM is implemented in C++ and interacts with the open-source linear solver COIN-OR Linear program Solver (CLP).", "The efficient calculation of elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs) is still a challenge. EFM-ta and treeefm are two different algorithms that use linear programming-based tree search and efficiently enumerates a subset of EFMs in GSMNs.", "Elementary flux modes (EFMs) are a key tool for analyzing genome-scale metabolic networks, and several methods have been proposed to compute them. Among them, those based on solving linear programming (LP) problems like TreeEFM and EFM-Ta are known to be very efficient if the main interest lies in computing large enough sets of EFMs.", "The efficient calculation of elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs) is a challenge. Two methods for this task have been developed, eFM-ta and treeefm." ], "exact_answer": [ [ "TreeEFM" ], [ "EFM-Ta" ] ], "type": "list", "id": "6027fcd31cb411341a0000ef", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 1136, "text": "Elementary flux modes (EFMs) analysis constitutes a fundamental tool in systems biology. However, the efficient calculation of EFMs in genome-scale metabolic networks (GSMNs) is still a challenge. We present a novel algorithm that uses a linear programming-based tree search and efficiently enumerates a subset of EFMs in GSMNs.RESULTS: Our approach is compared with the EFMEvolver approach, demonstrating a significant improvement in computation time. We also validate the usefulness of our new approach by studying the acetate overflow metabolism in the Escherichia coli bacteria. To do so, we computed 1 million EFMs for each energetic amino acid and then analysed the relevance of each energetic amino acid based on gene/protein expression data and the obtained EFMs. We found good agreement between previous experiments and the conclusions reached using EFMs. Finally, we also analysed the performance of our approach when applied to large GSMNs.AVAILABILITY AND IMPLEMENTATION: The stand-alone software TreeEFM is implemented in C++ and interacts with the open-source linear solver COIN-OR Linear program Solver (CLP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25380956", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 794, "text": "Elementary flux modes (EFMs) are a key tool for analyzing genome-scale metabolic networks, and several methods have been proposed to compute them. Among them, those based on solving linear programming (LP) problems are known to be very efficient if the main interest lies in computing large enough sets of EFMs.RESULTS: Here, we propose a new method called EFM-Ta that boosts the efficiency rate by analyzing the information provided by the LP solver. We base our method on a further study of the final tableau of the simplex method. By performing additional elementary steps and avoiding trivial solutions consisting of two cycles, we obtain many more EFMs for each LP problem posed, improving the efficiency rate of previously proposed methods by more than one order of magnitude.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32348455", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of vosoritide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31235532", "http://www.ncbi.nlm.nih.gov/pubmed/31269546" ], "ideal_answer": [ "Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification." ], "type": "summary", "id": "602747921cb411341a0000e0", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 897, "text": "TransCon CNP is a C-type natriuretic peptide (CNP-38) conjugated via a cleavable linker to a polyethylene glycol carrier molecule, designed to provide sustained systemic CNP levels upon weekly subcutaneous administration. TransCon CNP is in clinical development for the treatment of comorbidities associated with achondroplasia. In both mice and cynomolgus monkeys, sustained exposure to CNP via TransCon CNP was more efficacious in stimulating bone growth than intermittent CNP exposure. TransCon CNP was well tolerated with no adverse cardiovascular effects observed at exposure levels exceeding the expected clinical therapeutic exposure. At equivalent dose levels, reductions in blood pressure and/or an increase in heart rate were seen following single subcutaneous injections of the unconjugated CNP-38 molecule or a daily CNP-39 molecule (same amino acid sequence as Vosoritide, USAN:INN). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31235532", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 298, "text": "Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269546", "endSection": "abstract" }, { "offsetInBeginSection": 174, "offsetInEndSection": 288, "text": "ications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral oss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269546", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 299, "text": "Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269546", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 472, "text": "plications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification.METHODS: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269546", "endSection": "abstract" } ] }, { "body": "What is the \"flight-or-fight response\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25905810", "http://www.ncbi.nlm.nih.gov/pubmed/17615391", "http://www.ncbi.nlm.nih.gov/pubmed/19834455", "http://www.ncbi.nlm.nih.gov/pubmed/24704321" ], "ideal_answer": [ "This is also known as \" flight-or- fight response\" and is defined as an individual's response to a stimulus such as stress, that includes loss of sleep, anxiety, shortness of breath, muscle and joint pain.", "The cAMP intracellular signaling pathway is an important system for signal transmission responsible for the ancestral 'flight or fight' response and involved in the control of critical functions including frequency and strength of heart contraction, energy metabolism and gene transcription." ], "type": "summary", "id": "606b3ce794d57fd879000065", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Although the function of the autonomic nervous system (ANS) in mediating the flight-or-fight response was recognized decades ago, the crucial role of peripheral innervation in regulating cell behavior and response to the microenvironment has only recently emerged. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25905810", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 566, "text": " Beyond the \"flight-or-fight\" response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body (\"allostatic load\"). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17615391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The fear, flight or fight response serves as the fundamental physiological basis for examining an organism's awareness of its environment under an impending predator attack. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19834455", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 744, "text": "The cAMP intracellular signaling pathway is an important system for signal transmission responsible for the ancestral 'flight or fight' response and involved in the control of critical functions including frequency and strength of heart contraction, energy metabolism and gene transcription. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24704321", "endSection": "abstract" } ] }, { "body": "How is Burke-Fahn-Marsden Dystonia scale used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32252836", "http://www.ncbi.nlm.nih.gov/pubmed/21491490", "http://www.ncbi.nlm.nih.gov/pubmed/23549056", "http://www.ncbi.nlm.nih.gov/pubmed/21692107", "http://www.ncbi.nlm.nih.gov/pubmed/32796550", "http://www.ncbi.nlm.nih.gov/pubmed/28548593", "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "http://www.ncbi.nlm.nih.gov/pubmed/28661018", "http://www.ncbi.nlm.nih.gov/pubmed/32079672", "http://www.ncbi.nlm.nih.gov/pubmed/20207700", "http://www.ncbi.nlm.nih.gov/pubmed/21147544", "http://www.ncbi.nlm.nih.gov/pubmed/33084096", "http://www.ncbi.nlm.nih.gov/pubmed/32731476", "http://www.ncbi.nlm.nih.gov/pubmed/20697054", "http://www.ncbi.nlm.nih.gov/pubmed/27567612", "http://www.ncbi.nlm.nih.gov/pubmed/32441447", "http://www.ncbi.nlm.nih.gov/pubmed/31954905", "http://www.ncbi.nlm.nih.gov/pubmed/15264773", "http://www.ncbi.nlm.nih.gov/pubmed/31207377", "http://www.ncbi.nlm.nih.gov/pubmed/22258088", "http://www.ncbi.nlm.nih.gov/pubmed/31817799", "http://www.ncbi.nlm.nih.gov/pubmed/17274034", "http://www.ncbi.nlm.nih.gov/pubmed/33159411", "http://www.ncbi.nlm.nih.gov/pubmed/26616635", "http://www.ncbi.nlm.nih.gov/pubmed/27770067", "http://www.ncbi.nlm.nih.gov/pubmed/23408442", "http://www.ncbi.nlm.nih.gov/pubmed/24461258", "http://www.ncbi.nlm.nih.gov/pubmed/32386250", "http://www.ncbi.nlm.nih.gov/pubmed/17608320" ], "ideal_answer": [ "Burck-Fahn-Marsden Dystonia scale (BBS) is a simple, reliable, and valid measure of disease severity in patients with dystonia.", "Motor responses and disease severity in conditions such as cerebral palsy or other dystonias can be measured with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). This scale can be use to track surgery or treatment response.", "The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) including the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing.", "Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) includes the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing." ], "type": "summary", "id": "605258f494d57fd87900000c", "snippets": [ { "offsetInBeginSection": 269, "offsetInEndSection": 452, "text": "To estimate the minimal clinically important difference for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey in generalized or segmental dystonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32441447", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 525, "text": "Motor responses were measured with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32386250", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 600, "text": "The primary clinical outcome used was assessed by retrospective video analyses of patients' dystonia symptoms using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32252836", "endSection": "abstract" }, { "offsetInBeginSection": 517, "offsetInEndSection": 691, "text": "documenting pre-surgical and post-surgical assessments using the Burke-Fahn-Marsden Dystonia Rating Scale Motor Score (BFMMS) and Burke-Fahn-Marsden Disability Score (BFMDS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32079672", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 736, "text": "The disease severity was evaluated with Burke-Fahn-Marsden Dystonia Rating Scale and Toronto Western Spasmodic Torticollis Rating Scale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32731476", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 1036, "text": "ere treated by Gpi-DBS and 11 patients were treated by STN-DBS. All patients were assessed before surgery and at the last follow-up after surgery. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) including the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33159411", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 511, "text": "Bipallidal deep brain stimulation (DBS) resulted in a 55% reduction of dystonia severity assessed by the Burke-Fahn-Marsden scale score six months after surgery", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33084096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Background: The Burke-Fahn-Marsden Dystonia Rating Scale is a universally applied instrument for the quantitative assessment of dystonia in both children and adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 654, "text": "tor function was assessed using the Burke-Fahn-Marsden Dystonia Movement and Disability scales and the Barry Albright Dystonia Scale.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21491490", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 757, "text": "The aim is to demonstrate that in some cases of secondary dystonia, the sole use of impairment level measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, may be insufficient to fully evaluate outcome following deep brain stimulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258088", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 512, "text": "Deep brain stimulation outcomes are typically reported using impairment-focused measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, which provide little information about function and participation outcomes or changes in non-motor areas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258088", "endSection": "abstract" }, { "offsetInBeginSection": 1524, "offsetInEndSection": 1759, "text": "mates for the Burke-Fahn-Marsden Dystonia Rating Scale and the 36-Item Short-Form Health Survey may allow more reliable judgment of the clinical relevance of different treatments for segmental and generalized isolated dystonia. \u00a9 2020 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32441447", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 862, "text": "Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23408442", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 543, "text": "The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23408442", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 505, "text": "idated. Deep brain stimulation outcomes are typically reported using impairment-focused measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, which provide little information about function and participation outcomes or changes in non-motor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258088", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 284, "text": "l palsy. Today, the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) is mostly used to assess dystonia in children with inherited dy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32796550", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 253, "text": ". The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616635", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 754, "text": "eas. The aim is to demonstrate that in some cases of secondary dystonia, the sole use of impairment level measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, may be insufficient to fully evaluate outcome following deep brain stimulati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258088", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Background: The Burke-Fahn-Marsden Dystonia Rating Scale is a universally applied instrument for the quantitative assessment of dystonia in both childre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 716, "text": "ng the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Rating Scale, the authors evaluated the severity of patients' dystonia and related before surgery and at final follow-up during neurostimulation. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28548593", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 734, "text": "rological status and improvement in motor function resulting from DBS were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Implantati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15264773", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 682, "text": "ts were assessed before surgery and at the last follow-up after surgery using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) which includes both the movement and disability scales. Bilateral ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21147544", "endSection": "abstract" }, { "offsetInBeginSection": 658, "offsetInEndSection": 763, "text": "y and disability were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Disability sc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27567612", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 677, "text": "Reaching speed improved in response to injection, and dystonia scores on the Burke-Fahn-Marsden dystonia scale, the Unified Dystonia Rating Scale, and the Unified Parkinson's Disease Rating Scale improved.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17608320", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 514, "text": "LTS: Commonly used scales for clinical assessment are the Burke-Fahn-Marsden dystonia rating scale for generalized dystonia and the Toronto Western Spasmodic Torticollis Scale for cervical dystonia. Mo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21692107", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 597, "text": "UTCOME MEASURES: The primary outcome measures were the Burke-Fahn-Marsden Dystonia Scale (BFMDS) severity and disability scores, and the secondary outcome measure was the Unified Parkinson Disease Rating Scores.RESUL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20697054", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 574, "text": "he Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) were used to regularly assess changes in the patient's condition after DBS treatment.C", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31954905", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 776, "text": "he Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale was used to evaluate the severity of dystonia at three time points (before surgery, 3 months postoperatively, and the last available follow-up). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31207377", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 472, "text": "The Burke Fahn Marsden Dystonia Rating Scale served as an outcome measure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31817799", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 476, "text": "he Canadian Occupational Performance Measure (COPM) and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) were used as primary outcome measures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24461258", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 692, "text": "e searched PubMed for studies on genetically confirmed monogenic dystonia treated with GPi DBS documenting pre-surgical and post-surgical assessments using the Burke-Fahn-Marsden Dystonia Rating Scale Motor Score (BFMMS) and Burke-Fahn-Marsden Disability Score (BFMDS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32079672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Background: The Burke-Fahn-Marsden Dystonia Rating Scale is a universally applied instrument for the quantitative assessment of dystonia in both children and adults", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 696, "text": "he proportion of eye closure time was compared with 3 commonly used clinical rating scales: the Burke-Fahn-Marsden Dystonia Rating Scale, Global Dystonia Rating Scale, and Jankovic Rating Scale.R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27770067", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 481, "text": "THODS: Case series describing characteristics and outcomes based on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores before and after DBS at 3, 6 and at least 12 months.R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23549056", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1631, "text": "Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20207700", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1119, "text": "ependent of that, parents scored their children's functional motor development according to the Burke-Fahn-Marsden disability scale in another 52 healthy children (4-16 years of age; 2 boys and 2 girls per year of age). By", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 1262, "offsetInEndSection": 1619, "text": "s: In healthy children, assessment of physiologically immature motor performances by the Burke-Fahn-Marsden movement and disability scales showed an association between the outcomes of both scales and age (until 16 years and 12 years of age, \u03b2 = -0.72 and \u03b2 = -0.60, for Burke-Fahn-Marsden movement and disability scale, respectively [both P < 0.001]).Concl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "The Burke-Fahn-Marsden Dystonia Rating Scale is a universally applied instrument for the quantitative assessment of dystonia in both children and adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 1268, "offsetInEndSection": 1585, "text": "healthy children, assessment of physiologically immature motor performances by the Burke-Fahn-Marsden movement and disability scales showed an association between the outcomes of both scales and age (until 16 years and 12 years of age, \u03b2 = -0.72 and \u03b2 = -0.60, for Burke-Fahn-Marsden movement and disability scale, re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 896, "offsetInEndSection": 1081, "text": "dependent of that, parents scored their children's functional motor development according to the Burke-Fahn-Marsden disability scale in another 52 healthy children (4-16 years of age; 2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30838251", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 279, "text": "bral palsy. Today, the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) is mostly used to assess dystonia in children with inherit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32796550", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 248, "text": "ons. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional abi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26616635", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 1245, "text": "r at least 6 months. Motor function was assessed using the Burke-Fahn-Marsden Dystonia Movement and Disability scales and the Barry Albright Dystonia Scale.RESULTS: By 6 months, significant improvement was observed in the Burke-Fahn-Marsden Dystonia Movement scale (P=.004), the Burke-Fahn-Marsden Dystonia Disability scale (P=.027), and the Barry Albright Dystonia Scale (P=.029) for the whole cohort (n=14) and in the patients treated before skeletal maturity (group 1; n=8): Burke-Fahn-Marsden Dystonia Movement scale, P=.012; Burke-Fahn-Marsden Dystonia Disability scale, P=.020; and Barry Albright Dystonia Scale, P=.027.CONCLUSIONS: Deep brain stimulation may offer an effective treatment option for cerebral palsy-related dystonia, especially", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21491490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 481, "text": "BACKGROUND: The preoperative evaluation in dystonia aims at characterizing the severity and topography of motor symptoms in patients, who have previously been selected for deep brain stimulation (DBS).METHODS: The literature search was performed using PubMed, CINAHL, and the Cochrane Collaborative databases.RESULTS: Commonly used scales for clinical assessment are the Burke-Fahn-Marsden dystonia rating scale for generalized dystonia and the Toronto Western Spasmodic Torticolli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21692107", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 854, "text": "modic Torticollis Rating Scale). The presence and severity of dystonia were scored by four independent neurologists using the Burke-Fahn-Marsden Dystonia Rating Scale and Unified H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28661018", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 1628, "text": "r areas. The aim is to demonstrate that in some cases of secondary dystonia, the sole use of impairment level measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, may be insufficient to fully evaluate outcome following deep brain stimulation.METHODS: Six paediatric cases who underwent deep brain stimulation surgery with a minimum of one year follow up were selected on the basis of apparent non-response to deep brain stimulation, defined as a clinically insignificant change in the Burke-Fahn-Marsden Dystonia Movement Scale (<20%), but where other evaluation measures demonstrated clinical efficacy across several domains.RESULTS: Despite no significant change in Burke-Fahn-Marsden Dystonia Rating Scale scores following deep brain stimulation, parallel outcome measures demonstrated significant benefit in a range of child and family-centred goal areas including: pain and comfort, school attendance, seating tolerance, access to assistive technology and in some cases carer burden.CONCLUSIONS: Sole use of impairment-focused measures, are limited in scope to evaluate outcome following deep brain stimulati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22258088", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 693, "text": "BFM) scale. However, the reliability of this tool has rarely been evaluated and its use in a multicenter study has never been assessed prospectively.PURPOSE: To evaluate the concordance between three unblinded clinical raters and one single-blinded rater for 10 prospective series of ratings on the BFM scale in 22 dystonic patients of the SPIDY study.METHODS: Ten assessments on the BFM scale were performed under various stimulation conditions at different time points (before surgery and 1, 3,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17274034", "endSection": "abstract" } ] }, { "body": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15305245", "http://www.ncbi.nlm.nih.gov/pubmed/32876784", "http://www.ncbi.nlm.nih.gov/pubmed/24219041", "http://www.ncbi.nlm.nih.gov/pubmed/21044436", "http://www.ncbi.nlm.nih.gov/pubmed/9402864", "http://www.ncbi.nlm.nih.gov/pubmed/7482069", "http://www.ncbi.nlm.nih.gov/pubmed/32066940", "http://www.ncbi.nlm.nih.gov/pubmed/8535646", "http://www.ncbi.nlm.nih.gov/pubmed/26474779", "http://www.ncbi.nlm.nih.gov/pubmed/3741499", "http://www.ncbi.nlm.nih.gov/pubmed/8646434", "http://www.ncbi.nlm.nih.gov/pubmed/28081972", "http://www.ncbi.nlm.nih.gov/pubmed/3891280", "http://www.ncbi.nlm.nih.gov/pubmed/3913774", "http://www.ncbi.nlm.nih.gov/pubmed/29441860", "http://www.ncbi.nlm.nih.gov/pubmed/3913772", "http://www.ncbi.nlm.nih.gov/pubmed/26459854", "http://www.ncbi.nlm.nih.gov/pubmed/2388211", "http://www.ncbi.nlm.nih.gov/pubmed/24399184", "http://www.ncbi.nlm.nih.gov/pubmed/14963199", "http://www.ncbi.nlm.nih.gov/pubmed/23970326", "http://www.ncbi.nlm.nih.gov/pubmed/30081197", "http://www.ncbi.nlm.nih.gov/pubmed/22870474", "http://www.ncbi.nlm.nih.gov/pubmed/2080488", "http://www.ncbi.nlm.nih.gov/pubmed/27708921", "http://www.ncbi.nlm.nih.gov/pubmed/31866617", "http://www.ncbi.nlm.nih.gov/pubmed/7939730" ], "ideal_answer": [ "Yes, methotrexate is effective for the treatment of Rheumatoid Arthritis. MTX can be administered in combination with other chemotherapeutic agents or as mono-therapy. Response rate to MTX is more than 90%. MTX therapy is associated with improved survival of RA patients.", "The use of methotrexate in rheumatoid arthritis. Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis.", "Methotrexate (MTX) is clearly effective in the treatment of rheumatoid arthritis. MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies.", "Yes, methotrexate is used for the treatment of Rheumatoid Arthritis.", "Methotrexate is a cornerstone in the treatment of rheumatoid arthritis (RA). The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatic arthritis. It is considered a second-line disease modifying agent.", "Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis. Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis", "Yes. MTX is a folic acid antagonist that is approved for the management of severe active RA in patients who have had an insufficient therapeutic response to or are intolerant of an adequate trial of first-line therapy, including full-dose NSAIDs.", "Yes, methotrexate is effective for the treatment of Rheumatoid Arthritis.", "Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions.", "Yes. Methotrexate is used for the treatment of Rheumatoid Arthritis (RA) and other rheumatic diseases.", "Yes, methotrexate is a promising treatment option for the treatment of rheumatoid arthritis.", "Methotrexate (MTX) has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions." ], "exact_answer": "yes", "type": "yesno", "id": "5fe31304a43ad3127800003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "The use of methotrexate in rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3891280", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3913774", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3913774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3741499", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2388211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9402864", "endSection": "title" }, { "offsetInBeginSection": 639, "offsetInEndSection": 828, "text": "Methotrexate-induced hepatic cirrhosis is less common in rheumatoid arthritis than previously thought, although its occurrence in psoriasis is probably higher than in rheumatoid arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9402864", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 377, "text": "Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9402864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "The use of methotrexate in rheumatoid arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15305245", "endSection": "title" }, { "offsetInBeginSection": 177, "offsetInEndSection": 280, "text": "Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15305245", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 472, "text": "MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15305245", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24399184", "endSection": "abstract" }, { "offsetInBeginSection": 654, "offsetInEndSection": 890, "text": "A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24399184", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30081197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7482069", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The ai", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8646434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26459854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for second-line therapy of rheumatoid arthritis (RA). Althoug", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8535646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14963199", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 314, "text": "e suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23970326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "BACKGROUND: Treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccinat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28081972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29441860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Methotrexate (MTX) is known as a first-line synthetic disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31866617", "endSection": "abstract" }, { "offsetInBeginSection": 1239, "offsetInEndSection": 1431, "text": "Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26474779", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 129, "text": "Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 354, "text": "We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1304, "text": "st covered some but not all of the following areas: baseline \"pre-MTX\" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 576, "text": "lectronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32876784", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 650, "text": "MTX must at the present time be used only in severe RA, refractory to more than one classical slow acting drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2080488", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 538, "text": "MTX is as effective in treating RA as the other second line drugs and always more rapidly effective, perhaps because of anti-inflammatory properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2080488", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 257, "text": "For the low doses used in RA (less than 15 mg/week), MTX is completely and rapidly absorbed with an active process membrane transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2080488", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 183, "text": "Methotrexate, which is used for RA treatment, causes thrombocytopenia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921", "endSection": "title" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1245, "text": "This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 411, "text": "Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 893, "text": "We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27708921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Methotrexate (MTX) is the anchor treatment for rheumatoid arthritis (RA) and has been very thoroughly studied in many different patient populations, as monotherapy and in combination with various other disease modifying antirheumatic drugs and biologic agents, as they became available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24219041", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 465, "text": "Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3913772", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 405, "text": "Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32066940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32066940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "A number of studies show the efficacy of methotrexate (MTX) for rheumatoid arthritis (RA) in general.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7939730", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Methotrexate (MTX) is currently the most frequently used drugs in the treatment of rheumatoid arthritis (RA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21044436", "endSection": "abstract" } ] }, { "body": "What methodology does the FoundationOne CDx test use?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32393302" ], "ideal_answer": [ "FoundationOne CDx is a next generation sequencing (NGS) based test." ], "exact_answer": [ "next generation sequencing", "NGS" ], "type": "factoid", "id": "606b800994d57fd879000071", "snippets": [ { "offsetInBeginSection": 585, "offsetInEndSection": 748, "text": "Genetic alterations and TMB were determined by FoundationOne CDx next generation sequencing (NGS) and the association with clinicopathologic features was analyzed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32393302", "endSection": "abstract" } ] }, { "body": "Which R/bioconductor package exists for discovery of intergenic transcripts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32958497" ], "ideal_answer": [ "To increase the power of transcript discovery from large collection of RNA-seq data sets, a novel '1-Step' approach named pooling RNA-Seq and Assembling Models (PRAM) has been developed that build transcript models from pooled RNA- sequencing data sets. PRAM is implemented as an R/Bioconductor package.", "PRAM is a novel pooling approach for discoveries of intergenic transcripts from large-scale RNA sequencing experiments.", "PRAM is a novel pooling approach for discovering intergenic transcripts from large-scale RNA sequencing experiments. PRAM is implemented as an R/Bioconductor package. It covers raw reads alignment, RNA methylation site detection, motif discovery and functional analysis. More than 50% of reconstructed transcripts represent novel transcriptome elements, including 8,343 novel exons and exon extensions of annotated coding genes, 11,217 novel antisense transcripts and 29,541 novel intergenic transcript or their fragments showing canonical features of long non-coding RNAs (lncRNAs).", "Pooling RNA-seq and Assembling Models (PRAM) is a novel approach for discovering intergenic transcripts from large-scale RNA sequencing experiments. Applying PRAM to 30 human ENCODE RNA-seq data sets identified unannotated transcripts with epigenetic signatures similar to those of recently annotated transcripts.", "PRAM (Pooling RNA-seq and Assembling Models) is a novel pooling approach for discovering intergenic transcripts from large-scale RNA sequencing experiments." ], "exact_answer": [ "PRAM", "Pooling RNA-seq and Assembling Models" ], "type": "factoid", "id": "6060701c94d57fd87900003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "PRAM: a novel pooling approach for discovering intergenic transcripts from large-scale RNA sequencing experiments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32958497", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1535, "text": "Publicly available RNA-seq data is routinely used for retrospective analysis to elucidate new biology. Novel transcript discovery enabled by joint analysis of large collections of RNA-seq data sets has emerged as one such analysis. Current methods for transcript discovery rely on a '2-Step' approach where the first step encompasses building transcripts from individual data sets, followed by the second step that merges predicted transcripts across data sets. To increase the power of transcript discovery from large collections of RNA-seq data sets, we developed a novel '1-Step' approach named Pooling RNA-seq and Assembling Models (PRAM) that builds transcript models from pooled RNA-seq data sets. We demonstrate in a computational benchmark that 1-Step outperforms 2-Step approaches in predicting overall transcript structures and individual splice junctions, while performing competitively in detecting exonic nucleotides. Applying PRAM to 30 human ENCODE RNA-seq data sets identified unannotated transcripts with epigenetic and RAMPAGE signatures similar to those of recently annotated transcripts. In a case study, we discovered and experimentally validated new transcripts through the application of PRAM to mouse hematopoietic RNA-seq data sets. We uncovered new transcripts that share a differential expression pattern with a neighboring gene Pik3cg implicated in human hematopoietic phenotypes, and we provided evidence for the conservation of this relationship in human. PRAM is implemented as an R/Bioconductor package.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32958497", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of idasanutlin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33302031", "http://www.ncbi.nlm.nih.gov/pubmed/30536898", "http://www.ncbi.nlm.nih.gov/pubmed/30158012", "http://www.ncbi.nlm.nih.gov/pubmed/30755442", "http://www.ncbi.nlm.nih.gov/pubmed/30647052", "http://www.ncbi.nlm.nih.gov/pubmed/27353420", "http://www.ncbi.nlm.nih.gov/pubmed/29768700", "http://www.ncbi.nlm.nih.gov/pubmed/26586447", "http://www.ncbi.nlm.nih.gov/pubmed/26993060", "http://www.ncbi.nlm.nih.gov/pubmed/30352966", "http://www.ncbi.nlm.nih.gov/pubmed/29392451", "http://www.ncbi.nlm.nih.gov/pubmed/32629830", "http://www.ncbi.nlm.nih.gov/pubmed/29368050", "http://www.ncbi.nlm.nih.gov/pubmed/30700046", "http://www.ncbi.nlm.nih.gov/pubmed/32020437", "http://www.ncbi.nlm.nih.gov/pubmed/30511219", "http://www.ncbi.nlm.nih.gov/pubmed/31289443", "http://www.ncbi.nlm.nih.gov/pubmed/29857559", "http://www.ncbi.nlm.nih.gov/pubmed/31734832", "http://www.ncbi.nlm.nih.gov/pubmed/32167393", "http://www.ncbi.nlm.nih.gov/pubmed/33190064", "http://www.ncbi.nlm.nih.gov/pubmed/31167802" ], "ideal_answer": [ "Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53." ], "type": "summary", "id": "601cba001cb411341a000028", "snippets": [ { "offsetInBeginSection": 805, "offsetInEndSection": 986, "text": "In our panel of ten cell lines with a spectrum of aberrations in the p53 and pRb pathway, idasanutlin and abemaciclib were the most potent MDM2 and CDK4/6 inhibitors, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33190064", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 459, "text": "We evaluated idasanutlin-a new, potent murine double minute 2 antagonist-alone or with cytarabine in patients with r/r acute myeloid leukemia, de novo untreated acute myeloid leukemia unsuitable for standard treatment or with adverse features, or secondary acute myeloid leukemia in a multicenter, open-label, phase 1/1b trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33302031", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 168, "text": "Idasanutlin is a selective small-molecule MDM2 antagonist. It activates the tumor suppressor TP53 and is in phase 3 clinical trial for acute myeloid leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30511219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "High-risk neuroblastoma, a predominantly TP53 wild-type (wt) tumour, is incurable in >50% patients supporting the use of MDM2 antagonists as novel therapeutics. Idasanutlin (RG7388) shows in vitro synergy with chemotherapies used to treat neuroblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30536898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "The BCL2 inhibitor venetoclax plus the MDM2 inhibitor idasanutlin may be effective in treating relapsed/refractory acute myeloid leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30647052", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 650, "text": "The small molecule RG7388 (idasanutlin, R05503781) is a newly developed inhibitor that is specific for an oncogene-derived protein called MDM2, which is also in clinical trials for the treatment of various types of cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30700046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31734832", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Purpose MDM2 is a negative regulator of the tumor suppressor p53. RO6839921 is an inactive pegylated prodrug of idasanutlin, an MDM2 antagonist, developed for intravenous administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31734832", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 281, "text": "RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32020437", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 222, "text": "Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32167393", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1055, "text": "ter treatment of p53wt cells with idasanutlin (RG7388, RO5503781), which is the only MDM2 antagonist that has passed phase II and entered phase III clinical trials, so far. Idasanutlin strongly activates p53, as evidenced by the induction of p21 expression and pot", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30352966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "PURPOSE: Idasanutlin is a selective small-molecule MDM2 antagonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30511219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27353420", "endSection": "title" }, { "offsetInBeginSection": 66, "offsetInEndSection": 186, "text": "RO6839921 is an inactive pegylated prodrug of idasanutlin, an MDM2 antagonist, developed for intravenous administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31734832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "MDM2 antagonists as a novel treatment option for acute myeloid leukemia: perspectives on the therapeutic potential of idasanutlin (RG7388).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31289443", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "PURPOSE: Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 ac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29368050", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 638, "text": "nd metastasis. The small molecule RG7388 (idasanutlin, R05503781) is a newly developed inhibitor that is specific for an oncogene-derived protein called MDM2, which is also in clinical trials for the treatment of various types", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30700046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The BCL2 inhibitor venetoclax plus the MDM2 inhibitor idasanutlin may be effective in treating relapsed/refractory acute myeloid leukemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30647052", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1125, "text": "When combined with imidazoline MDM2 inhibitors (Nutlin-3a and Idasanutlin/RG-7388), synergism was observed in cancer cell growth inhibition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32629830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations, and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29368050", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 280, "text": "RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32020437", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 114, "text": "Idasanutlin (RG7388) is a potent p53-MDM2 antagonist currently in clinical development for treatment of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Efficient Industrial Synthesis of the MDM2 Antagonist Idasanutlin via a Cu(I)-catalyzed [3+2] Asymmetric Cycloaddition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30158012", "endSection": "title" }, { "offsetInBeginSection": 530, "offsetInEndSection": 762, "text": "Here we assessed the MDM2 antagonist idasanutlin and the MEK1 inhibitor cobimetinib as single agents and in combination in a variety of AML cell lines and primary AML blast cells for their ability to induce apoptosis and cell death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29857559", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Investigating the effect of autoinduction in cynomolgus monkeys of a novel anticancer MDM2 antagonist, idasanutlin, and relevance to humans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26586447", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "PURPOSE: Idasanutlin is a selective small-molecule MDM2 antagonist", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30511219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "PURPOSE: Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29392451", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 797, "text": "Therefore, we performed an investigator-initiated phase 1 trial of the oral MDM2 antagonist idasanutlin (RG7388; Roche) in patients with high-risk PV/ET for whom at least 1 prior therapy had failed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31167802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2-selective antagonist idasanutlin (RG7388).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26993060", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "OBJECTIVES: To investigate whether the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) combined with the selective MDM2 antagonist idasanutlin (RG7388) offers superior efficacy to monotherapy in treating B-lymphoid malignancies in preclinical models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26993060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Venetoclax (ABT-199) and idasanutlin (RG7388) are efficient anticancer drugs targeting two essential apoptosis markers, Bcl-2 and MDM2, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29768700", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 659, "text": "We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin (MDM2-specific) and ATSP-7041 (MDM2/4-dual), we show that MRT cells were more sensitive than other p53 wild-type cancer cell lines to inhibition of MDM2 alone as well as dual inhibition of MDM2/4. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30755442", "endSection": "abstract" } ] }, { "body": "Where is corticosterone synthesized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30318934", "http://www.ncbi.nlm.nih.gov/pubmed/32347034", "http://www.ncbi.nlm.nih.gov/pubmed/31953122", "http://www.ncbi.nlm.nih.gov/pubmed/32047871", "http://www.ncbi.nlm.nih.gov/pubmed/31972205" ], "ideal_answer": [ "Following a stressful event, the hypothalamus-pituitary-adrenal axis mediates the release of the stress hormone cortisol (corticosterone in rodents; CORT)." ], "exact_answer": [ "Adrenal glands" ], "type": "factoid", "id": "606b390f94d57fd879000062", "snippets": [ { "offsetInBeginSection": 1094, "offsetInEndSection": 1298, "text": ", the adrenal levels of aldosterone, corticosterone, and pituitary adrenocorticotropic hormone (ACTH) were determined as crucial indicators of the hypothalamic-pituitaryadrenocortical (HPA) axis activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32347034", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 426, "text": "stress stimulated adrenocortical activity ultrastructurally with an elevation of corticosterone level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30318934", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Following a stressful event, the hypothalamus-pituitary-adrenal axis mediates the release of the stress hormone cortisol (corticosterone in rodents; CORT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31953122", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 204, "text": "Higher levels of glucocorticoids (GCs), and impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis may cause or exacerbate the occurrence of metabolic and psychiatric disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31972205", "endSection": "abstract" }, { "offsetInBeginSection": 538, "offsetInEndSection": 590, "text": "(adrenal glucocorticoids [cortisol, corticosterone],", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32047871", "endSection": "abstract" } ] }, { "body": "Where is the klotho protein primarily expressed in the body", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19184092", "http://www.ncbi.nlm.nih.gov/pubmed/9791011", "http://www.ncbi.nlm.nih.gov/pubmed/23838326", "http://www.ncbi.nlm.nih.gov/pubmed/32466632", "http://www.ncbi.nlm.nih.gov/pubmed/23928372", "http://www.ncbi.nlm.nih.gov/pubmed/32347987", "http://www.ncbi.nlm.nih.gov/pubmed/23375286", "http://www.ncbi.nlm.nih.gov/pubmed/15665504", "http://www.ncbi.nlm.nih.gov/pubmed/32052504", "http://www.ncbi.nlm.nih.gov/pubmed/22396165", "http://www.ncbi.nlm.nih.gov/pubmed/23748218", "http://www.ncbi.nlm.nih.gov/pubmed/30233703", "http://www.ncbi.nlm.nih.gov/pubmed/12204354", "http://www.ncbi.nlm.nih.gov/pubmed/32005658", "http://www.ncbi.nlm.nih.gov/pubmed/31920703", "http://www.ncbi.nlm.nih.gov/pubmed/17287345", "http://www.ncbi.nlm.nih.gov/pubmed/28709936", "http://www.ncbi.nlm.nih.gov/pubmed/29053774", "http://www.ncbi.nlm.nih.gov/pubmed/19464978", "http://www.ncbi.nlm.nih.gov/pubmed/31928223", "http://www.ncbi.nlm.nih.gov/pubmed/31951006", "http://www.ncbi.nlm.nih.gov/pubmed/32479899", "http://www.ncbi.nlm.nih.gov/pubmed/33179086", "http://www.ncbi.nlm.nih.gov/pubmed/32438076", "http://www.ncbi.nlm.nih.gov/pubmed/30358003", "http://www.ncbi.nlm.nih.gov/pubmed/25466545", "http://www.ncbi.nlm.nih.gov/pubmed/24457979", "http://www.ncbi.nlm.nih.gov/pubmed/22338062", "http://www.ncbi.nlm.nih.gov/pubmed/26307633", "http://www.ncbi.nlm.nih.gov/pubmed/21496980", "http://www.ncbi.nlm.nih.gov/pubmed/16358222", "http://www.ncbi.nlm.nih.gov/pubmed/12362891" ], "ideal_answer": [ "The klotho protein is primarily expressed in the lungs, kidney, lens, cerebellum, trpc6, renal cells and the brain.", "Klotho is primarily expressed in the kidney but also in the brain, lens of the eye, and heart.", "Klotho is primarily expressed in the lungs, kidney, lens, cerebellum, trpc6, renal cells and the brain." ], "exact_answer": [ [ "kidney" ], [ "brain", "cerebellum", "choroid plexus" ], [ "heart" ], [ "eye", "lens" ], [ "parathyroid" ], [ "inner ear" ], [ "reproductive organs", "ovaries" ], [ "intestine" ], [ "lens", "eye" ] ], "type": "list", "id": "6060996394d57fd879000045", "snippets": [ { "offsetInBeginSection": 395, "offsetInEndSection": 559, "text": "The present study explored the relevance of the aging suppressor, Klotho, which has anti\u2011aging activity and is highly expressed in murine renal cells/kidney tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33179086", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 220, "text": "rming growth factor-\u03b2 (TGF-\u03b2) and insulin-like growth factor (IGF). Renal expression of klotho is diminished in polycystic kidney disease (PKD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31928223", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 426, "text": "One of the crucial symptoms is pulmonary emphysema, although \u03b1-Klotho is not expressed in the lungs. \u03b1-Klotho secreted from the kidneys is probably involved in the pathology of emphysema because kidney-specific knockout mice exhibit emphysematous structural changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31951006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "The fortuitously discovered antiaging membrane protein \u03b1Klotho (Klotho) is highly expressed in the kidney, and deletion of the Klotho gene in mice causes a phenotype strikingly similar to that of chronic kidney disease (CKD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32005658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "High-intensity interval training increases myocardial levels of Klotho and protects the heart against ischaemia-reperfusion injury.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32052504", "endSection": "title" }, { "offsetInBeginSection": 434, "offsetInEndSection": 723, "text": "he increase of plasma and myocardial levels of Klotho as a result of preconditioning with HIIT and prevention of a significant reduction of Klotho during IR injury can promote cardioprotection and reduce damage by attenuating myocardial TRPC6 expression and increasing antioxidant defence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32052504", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 210, "text": "Klotho is an anti-aging protein expressed in Purkinje cells of the cerebellum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32479899", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 260, "text": "Klotho is expressed in limited tissues including the lens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32438076", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 637, "text": "Thus, upregulating Klotho in the brain may lead to novel therapeutics to people suffering or at risk for neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, and demyelinating diseases such as multiple sclerosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32347987", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 622, "text": "Klotho, a transmembrane protein expressed primarily in renal tubules, functions as an obligatory co-receptor for FGF-23.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23748218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Klotho is a protein primarily expressed in renal tubular epithelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30358003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "BACKGROUND: Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long extracellular domain, which can be cleaved and released as a soluble form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23375286", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Klotho is a transmembrane protein expressed primarily in kidney, parathyroid gland, and choroid plexus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24457979", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The Klotho gene has been identified as an aging suppressor gene that encodes a transmembrane protein, which is expressed primarily in renal tubules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22338062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Klotho is a putative aging suppressor gene that is primarily expressed in renal tubular epithelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32466632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "Klotho, an antiaging gene with restricted organ distribution, is mainly expressed in the kidney tubules; the mutant mice have shortened life span, arteriosclerosis, anemia, and osteoporesis, features common to patients with chronic renal failure. Concei", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17287345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Klotho, a membrane protein mainly expressed in parathyroid glands, kidney, and choroid plexus, counteracts aging and increases the life span. Accor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19184092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "UNLABELLED: Klotho, a protein expressed mainly in the kidney, is required for the inhibitory effect of FGF23 on renal 1,25(OH)2D3 form", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26307633", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 681, "text": "ing of FGF23 to a FGF receptor requires a protein named Klotho that is expressed in the kidney in the distal but not in the proximal tubule. The mech", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19464978", "endSection": "abstract" }, { "offsetInBeginSection": 106, "offsetInEndSection": 182, "text": "lotho, an anti-aging gene, is mainly expressed in the brain and kidney. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Klotho is a membrane-bound protein predominantly expressed in the kidney, where it acts as a permissive co-receptor for Fibroblast Growth Factor 23.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28709936", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 663, "text": "Klotho protein was mainly expressed in the stria vascularis and spiral ligament of the inner ear and in the distal convoluted tubule of the kidney, likely serving a common function in the two organs, i.e., modulating ion transport.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12204354", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The antiaging protein of Klotho is a transmembrane protein mainly expressed in the kidney, parathyroid glands and choroid plexus of the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25466545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND: The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29053774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Klotho is a recently discovered anti-aging gene and is primarily expressed in kidneys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23928372", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 341, "text": "Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23838326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "BACKGROUND: Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long extracellular domain, which can be cleaved and released as a soluble form", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23375286", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 669, "text": "Klotho also is expressed in the parathyroid gland, where FGF-23 decreases parathyroid hormone expression and secretion, further suppressing vitamin D synthesis in kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21496980", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Expression of klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23838326", "endSection": "title" }, { "offsetInBeginSection": 342, "offsetInEndSection": 502, "text": "Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23838326", "endSection": "abstract" }, { "offsetInBeginSection": 851, "offsetInEndSection": 997, "text": "Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23838326", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 177, "text": "Klotho, an anti-aging gene, is mainly expressed in the brain and kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233703", "endSection": "abstract" }, { "offsetInBeginSection": 267, "offsetInEndSection": 385, "text": "Klotho mRNA, however, is expressed only in brain, kidney, reproductive organs, pituitary gland, and parathyroid gland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15665504", "endSection": "abstract" }, { "offsetInBeginSection": 759, "offsetInEndSection": 887, "text": "Our results confirmed that the full-length (130 kDa) and shorter-form (65 kDa) \u03b1-klotho were primarily expressed in the kidneys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31920703", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 738, "text": "Northern blot analysis using the rat klotho cDNA probe identified a single transcript of 5.2 kb in size expressed predominantly in the kidney, while RT-PCR detected low levels of expression also in the brain, lung, intestine, and ovaries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9791011", "endSection": "abstract" }, { "offsetInBeginSection": 775, "offsetInEndSection": 929, "text": "In brain, Klotho proteins were localized at choroid plexus, where the proteins were dominantly localized at the apical plasma membrane of ependymal cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15665504", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1067, "text": "Moreover, we found that, except for the kidneys and brain, other tissues primarily expressed the shorter-form \u03b1-klotho, including liver, which was in contrast to previous reports.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31920703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Klotho is an anti-aging protein predominantly expressed in the kidney, parathyroid glands and choroid plexus of the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22396165", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 691, "text": "Furthermore, the klotho gene is expressed principally in the important tissues for calcium homeostasis such as distal tubule cells of the kidney, choroid plexus in the brain, and the main cells of the parathyroid gland.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12362891", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 989, "text": "The klotho gene is predominantly expressed in the kidney and the expression level of klotho RNA was shown to be greatly reduced in the kidneys of chronic renal failure (CRF) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16358222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The klotho gene: a gene predominantly expressed in the kidney is a fundamental regulator of aging and calcium/phosphorus metabolism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16358222", "endSection": "title" }, { "offsetInBeginSection": 493, "offsetInEndSection": 683, "text": "Klotho mRNA and protein expression levels in rat brain and kidney tissues were examined using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30233703", "endSection": "abstract" } ] }, { "body": "Which particular intersex phenotype is related to steroid reductase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21893969", "http://www.ncbi.nlm.nih.gov/pubmed/31981690", "http://www.ncbi.nlm.nih.gov/pubmed/9247984", "http://www.ncbi.nlm.nih.gov/pubmed/24383016", "http://www.ncbi.nlm.nih.gov/pubmed/11392378", "http://www.ncbi.nlm.nih.gov/pubmed/25077171", "http://www.ncbi.nlm.nih.gov/pubmed/21714467", "http://www.ncbi.nlm.nih.gov/pubmed/8723114", "http://www.ncbi.nlm.nih.gov/pubmed/8262007" ], "ideal_answer": [ "Steroid reductase mutations are associated with both sex-determining and non-syndromic hypospadias", "Virilization of the external genitalia in the male fetus requires testosterone and dihydrotestosterone (DHT), which is formed from testosterone by the action of the enzyme, 5alpha-reductase type 2 (5alphaR-2). Numerous cases of male pseudohermaphroditism due to 5 alpha reductase-2 deficiency have been identified.", "Mutations in the steroid 5 alpha-reductase 2 gene are the cause of 5 alpha reductase deficiency. In the 20 yr since it was established that impairment of dihydrotestosterone formation is a cause of a rare form of human intersex, a wealth of information has accumulated about the genetics, endocrinology, and variable phenotypic manifestations.", "Hypospadias is a rare form of intersex due to reduced activity of steroid reductase 5 alpha-reductase." ], "exact_answer": [ "male pseudohermaphroditism" ], "type": "factoid", "id": "5fd779b4a43ad31278000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Gender identity and role in a pedigree of Arabs with intersex due to 5 alpha reductase-2 deficiency", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9247984", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Between 1986 and 1995, a pedigree of six Arabs with male pseudohermaphroditism due to 5 alpha reductase-2 deficiency have been identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9247984", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 441, "text": "In the 20 yr since it was established that impairment of dihydrotestosterone formation is the cause of a rare form of human intersex, a wealth of information has accumulated about the genetics, endocrinology, and variable phenotypic manifestations, culminating in the cloning of cDNAs encoding two 5 alpha-reductase genes and documentation that mutations in the steroid 5 alpha-reductase 2 gene are the cause of 5 alpha-reductase deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8262007", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 988, "text": "It is also imperative to establish whether defects in steroid 5 alpha-reductase 2, perhaps in the heterozygous state, are responsible for a portion of cases of sporadic hypospadias, to determine whether 5 alpha-reductase plays a role in progesterone action in women, and to elucidate the relation between androgen action and gender role behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8262007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Virilization of the external genitalia in the male fetus requires testosterone and dihydrotestosterone (DHT), which is formed from testosterone by the action of the enzyme, 5alpha-reductase type 2 (5alphaR-2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11392378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Steroid 5-alpha-reductase 2 deficiency is an autosomal recessive disorder with clinical spectrum ranges from a male phenotype with hypospadia to a female phenotype with normal wolffian structures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21714467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Steroid 5-alpha-reductase 2 deficiency is a rare disorder leading to male pseudohermaphroditism, a condition characterized by incomplete differentiation of male genitalia in 46,XY patients. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24383016", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 879, "text": "ch impairs DHT formation (mutation within the 5alphaR-2 gene or 5alphaR-2 inhibitors) or normal function of the AR (mutation in the AR gene, antiandrogens) may result in insufficient androgen action in the male fetus and in subsequent undervirilization in the newborn. Hypospadias may ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11392378", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1420, "text": "oding sequences of the SRY gene (case 1) and 2 candidates for monogenic hypospadias, namely MAMLD1 (mastermind-like domain containing 1) and SRD5A2 (steroid-5-alpha-reductase, alpha polypeptide 2). Sequencing of the entire SRY gene, incl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "In 1974, a lack of 5\u03b1-dihydrotestosterone (5\u03b1-DHT), the most potent androgen across species except for fish, was shown to be the origin of a type of pseudohermaphrodism in which boys have female-like external genitalia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31981690", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1380, "text": "Molecular studies were focused on coding sequences of the SRY gene (case 1) and 2 candidates for monogenic hypospadias, namely MAMLD1 (mastermind-like domain containing 1) and SRD5A2 (steroid-5-alpha-reductase, alpha polypeptide 2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893969", "endSection": "abstract" }, { "offsetInBeginSection": 1839, "offsetInEndSection": 2042, "text": "None of the identified polymorphisms cosegregated with the intersexual phenotype, thus, we cannot confirm that hypospadias may be associated with polymorphism in the coding sequence of the studied genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893969", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 779, "text": "This animal was classified as a compound sex reversal (78,XX, SRY-negative) with the hypospadias syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Hypospadias in a male (78,XY; SRY-positive) dog and sex reversal female (78,XX; SRY-negative) dogs: clinical, histological and genetic studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21893969", "endSection": "title" }, { "offsetInBeginSection": 1622, "offsetInEndSection": 1881, "text": "Hence, steroid 5 alpha-reductase deficiency should be considered not only in sex reversed patients with female or ambiguous phenotypes, but also in those with mild symptoms of undermasculinization as encountered in patients with hypospadias and/or micropenis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8723114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8723114", "endSection": "title" }, { "offsetInBeginSection": 1882, "offsetInEndSection": 2224, "text": "A classification based on the severity of the masculinization defect may be used for correlation of phenotypes with enzyme activities and genotypes, and for comparisons of phenotypes between different patients as the basis for clinical decisions to be made in patients with pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8723114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Inactivating mutations of the 5\u03b1-steroid reductase type-2 (SRD5A2) gene result in a broad spectrum of masculinization defects, ranging from a male phenotype with hypospadias to a female phenotype with Wolffian structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25077171", "endSection": "abstract" } ] }, { "body": "Is atenolol metabolized by CYP2D6?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20406225" ], "ideal_answer": [ "No, atenolol is metabolized in a CYP2D6-independent manner." ], "exact_answer": "no", "type": "yesno", "id": "605e3c8294d57fd879000037", "snippets": [ { "offsetInBeginSection": 452, "offsetInEndSection": 839, "text": "The study analysed the prescribing and dispensing of CYP2D6 drugs (metoprolol, donepezil, galantamine, codeine, tamoxifen) together with CYP2D6-blocking SSRIs (paroxetine/fluoxetine) or SSRIs without significant CYP2D6 inhibition (citalopram/escitalopram/sertraline), and the related prescribing of CYP2D6-independent comparator drugs (atenolol, rivastigmine, propoxyphene, anastrozole).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20406225", "endSection": "abstract" } ] }, { "body": "Describe DeepTRIAGE", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32093737" ], "ideal_answer": [ "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, placing all luminal samples along a continuum of severity.", "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture, which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, placed all luminal samples along a continuum of severity.", "Accurately differentiating between breast cancer sub-types is an important part of clinical decision-making. DeepTRIAGE uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample.", "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture, which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, place all luminal samples along a continuum of severity, and assess whether the major principal axis associate with known clinical phenotypes.", "DeepTRIAGE is an algorithm that uses machine learning to classify breast cancer sub-types. Basically, it takes a bunch of different subtypes of breast cancer, each with a distinct molecular signature that correlates with patient prognosis, and gives a score that describes how important each gene is in predicting the sub-type for each sample.", "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture, which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, determining all luminal samples along a continuum of severity.", "Breast cancer is a collection of multiple tissue pathologies, each with a distinct molecular signature that correlates with patient prognosis and response to therapy. Accurately differentiating between breast cancer sub-types is an important part of clinical decision-making. Although this problem has been addressed using machine learning methods in the past, there remains unexplained heterogeneity within the established sub-types that cannot be resolved by the commonly used classification algorithms. DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is novel deep learning architecture which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample." ], "type": "summary", "id": "601eba711cb411341a000059", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "DeepTRIAGE: interpretable and individualised biomarker scores using attention mechanism for the classification of breast cancer sub-types.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32093737", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1067, "text": "Breast cancer is a collection of multiple tissue pathologies, each with a distinct molecular signature that correlates with patient prognosis and response to therapy. Accurately differentiating between breast cancer sub-types is an important part of clinical decision-making. Although this problem has been addressed using machine learning methods in the past, there remains unexplained heterogeneity within the established sub-types that cannot be resolved by the commonly used classification algorithms.METHODS: In this paper, we propose a novel deep learning architecture, called DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression), which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. We then perform a principal component analysis of these biomarker scores to visualise the sample heterogeneity, and use a linear model to test whether the major principal axes associate with known clinical phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32093737", "endSection": "abstract" } ] }, { "body": "What is Pseudomelanosis duodeni?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/3371613", "http://www.ncbi.nlm.nih.gov/pubmed/10998854", "http://www.ncbi.nlm.nih.gov/pubmed/22493558", "http://www.ncbi.nlm.nih.gov/pubmed/27785200", "http://www.ncbi.nlm.nih.gov/pubmed/3047212", "http://www.ncbi.nlm.nih.gov/pubmed/31528551", "http://www.ncbi.nlm.nih.gov/pubmed/27701885", "http://www.ncbi.nlm.nih.gov/pubmed/8527967", "http://www.ncbi.nlm.nih.gov/pubmed/28679982", "http://www.ncbi.nlm.nih.gov/pubmed/10958041", "http://www.ncbi.nlm.nih.gov/pubmed/18253910", "http://www.ncbi.nlm.nih.gov/pubmed/29564071", "http://www.ncbi.nlm.nih.gov/pubmed/9050065", "http://www.ncbi.nlm.nih.gov/pubmed/24326430", "http://www.ncbi.nlm.nih.gov/pubmed/10532135", "http://www.ncbi.nlm.nih.gov/pubmed/1341423", "http://www.ncbi.nlm.nih.gov/pubmed/32313471" ], "ideal_answer": [ "Pseudomelanosis duodeni is a rare incidental finding seen on endoscopy and has the characteristic appearance of flat, black-speckled pigmented mucosa that can be associated with gastrointestinal bleeding, hypertension, chronic heart failure, chronic renal failure and consumption of different drugs." ], "type": "summary", "id": "601c4a0a1cb411341a00001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Pseudomelanosis duodeni is a rare incidental finding seen on endoscopy and has the characteristic appearance of flat, black-speckled pigmented mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32313471", "endSection": "abstract" }, { "offsetInBeginSection": 462, "offsetInEndSection": 552, "text": "Esophagogastroduodenoscopy revealed a brownish speckled pigmentation in the duodenal bulb.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28679982", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 598, "text": "Besides a Schatzki's ring the EGD revealed a duodenal mucosa with black-speckled pigmentation. Biopsies were performed and disclosed the deposition of brown (hemosiderin) pigment within macrophages in the lamina propria of normal villi. This endoscopic appearance is called pseudomelanosis duodeni (PD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27701885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Pseudomelanosis duodeni is a rare entity characterised by dark pigmented intracellular granules seen within macrophages that lie within the lamina propria of the duodenal villi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24326430", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Pseudomelanosis duodeni (PD) is a rare dark speckled appearance of the duodenum associated with gastrointestinal bleeding, hypertension, chronic heart failure, chronic renal failure and consumption of different drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22493558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Pseudomelanosis duodeni is a rare, benign condition of unknown etiology. It is characterized by collection of pigment-laden macrophages in the tips of duodenal villi. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27785200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Pseudomelanosis duodeni is seen endoscopically as dark spots in the duodenal mucosa and is generally considered to be local deposition of iron from oral iron intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18253910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Pseudomelanosis duodeni is a rare condition in which dark pigment accumulates in macrophages located in the lamina propria of the duodenal mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3371613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Pseudomelanosis duodeni is an uncommon endoscopic sign characterized by diffuse small black spots on the first and second portions of the duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8527967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Pseudomelanosis duodeni is a rare incidental finding seen on endoscopy and has the characteristic appearance of flat, black-speckled pigmented mucosa. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32313471", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Pseudomelanosis duodeni is an uncommon endoscopic sign characterized by diffuse small black spots on the first and second portions of the duodenum. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8527967", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Pseudomelanosis duodeni is a rare condition in which dark pigment accumulates in macrophages located in the lamina propria of the duodenal mucosa. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3371613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Pseudomelanosis duodeni is a rare entity characterized by dark pigmentation of duodenal mucosa of uncertain etiology and clinical significance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10532135", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Duodenal pseudomelanosis (or pseudomelanosis duodeni) is a rare benign condition characterized by black-brown speckled pigmentation of the duodenal mucosa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31528551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Pseudomelanosis duodeni, speckled black pigmentation of the duodenal mucosa, presents a striking appearance at endoscopy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3047212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Pseudomelanosis duodeni is a rare benign condition. It manifests endoscopically as discrete, flat, small brown-black spots in the duodenal mucosa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10958041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Despite the common practice of upper gastrointestinal endoscopy, the unique phenomenon of punctate black pigmentation of the duodenal mucosa, now known as pseudomelanosis duodeni, still remains a rare entity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1341423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Pseudomelanosis duodeni is rarely seen in children. It manifests endoscopically as peppery speckles in the duodenal mucosa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9050065", "endSection": "abstract" } ] }, { "body": "Is the glucocorticoid receptor a transcription factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32487073", "http://www.ncbi.nlm.nih.gov/pubmed/31776270", "http://www.ncbi.nlm.nih.gov/pubmed/31689103" ], "ideal_answer": [ "Yes,\nThe glucocorticoid receptor (GR) is a ligand-activated transcription factor that translocates to the nucleus upon hormone stimulation and distributes between the nucleoplasm and membraneless compartments named nuclear foci." ], "exact_answer": "yes", "type": "yesno", "id": "606b3b6794d57fd879000064", "snippets": [ { "offsetInBeginSection": 829, "offsetInEndSection": 877, "text": "GR and KLF4, both pioneer transcription factors,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "The glucocorticoid receptor (GR) is a ligand-binding dependent transcription factor that ultimately regulates vital biological processes and inflammation response through specific gene expression control, thus representing a notable drug target to explore. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31689103", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 439, "text": "The glucocorticoid receptor (GR) is a ligand-activated transcription factor that translocates to the nucleus upon hormone stimulation and distributes between the nucleoplasm and membraneless compartments named nuclear foci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32487073", "endSection": "abstract" } ] }, { "body": "What are the five traits associated with metabolic syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17918262", "http://www.ncbi.nlm.nih.gov/pubmed/24260389", "http://www.ncbi.nlm.nih.gov/pubmed/29502759", "http://www.ncbi.nlm.nih.gov/pubmed/32562864", "http://www.ncbi.nlm.nih.gov/pubmed/20694148", "http://www.ncbi.nlm.nih.gov/pubmed/25104441", "http://www.ncbi.nlm.nih.gov/pubmed/19137372", "http://www.ncbi.nlm.nih.gov/pubmed/20021073", "http://www.ncbi.nlm.nih.gov/pubmed/25612864", "http://www.ncbi.nlm.nih.gov/pubmed/12240700", "http://www.ncbi.nlm.nih.gov/pubmed/31637139", "http://www.ncbi.nlm.nih.gov/pubmed/26175188", "http://www.ncbi.nlm.nih.gov/pubmed/18489847", "http://www.ncbi.nlm.nih.gov/pubmed/16305067", "http://www.ncbi.nlm.nih.gov/pubmed/15157122", "http://www.ncbi.nlm.nih.gov/pubmed/26956847", "http://www.ncbi.nlm.nih.gov/pubmed/20018034", "http://www.ncbi.nlm.nih.gov/pubmed/14975163" ], "ideal_answer": [ "Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension.", "Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors. These factors include obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension.", "Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension", "Metabolic syndrome is the concurrent presentation of multiple cardiovascular factors, including obesity, insulin resistance, type 1 diabetes, type 2 diabetes, and hypertension.", "Metabolic syndrome is a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes. These conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels.", "Metabolic syndrome (MetS) is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, insulin resistance, hypertension, dyslipidemia and hyperglycemia.", "Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, insulin resistance, hypertension, dyslipidemia and hyperglycemia." ], "exact_answer": [ [ "obesity" ], [ "insulin resistance" ], [ "dyslipidemia" ], [ "hypertension", "cardiovascular risk factors" ], [ "hyperglycemia" ] ], "type": "list", "id": "601ff55a1cb411341a000077", "snippets": [ { "offsetInBeginSection": 21, "offsetInEndSection": 195, "text": "Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32562864", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 686, "text": "THODS: We measured personality traits using the Japanese version of the Eysenck Personality Questionnaire (Revised Short Form) and five metabolic syndrome components-elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose-in 1322 participants aged 51.1\u00b112.7years old from Kakegawa city, Japan. M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29502759", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 1025, "text": " Therefore, to demonstrate the utility of both univariate and multivariate family-based association analysis and to identify possible genetic variants associated with metabolic syndrome, we performed a scan of the Affymetrix 50 k Human Gene Panel data using 1) each of the traits comprising metabolic syndrome: triglycerides, high-density lipoprotein, systolic blood pressure, diastolic blood pressure, blood glucose, and body mass index, and 2) a composite trait including all of the above, jointly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20018034", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "The metabolic syndrome represents a cluster of closely connected premorbid risk factors or diseases with visceral obesity type 2 diabetes, hypertension and low HLD/hypertriglyceridemia as established traits affecting about 20% in the adult European populations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25612864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Obesity is associated with increased susceptibility to dyslipidemia, insulin resistance, and hypertension, a combination of traits that comprise the traditional definition of the metabolic syndrome. R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19137372", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 654, "text": " is now widely recognised that obesity (especially abdominal fat accumulation), hyperglycaemia, dyslipidaemia and hypertension are common metabolic traits that, concurrently, constitute the distinctive insulin resistance or metabolic syndrome. Cross", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15157122", "endSection": "abstract" }, { "offsetInBeginSection": 748, "offsetInEndSection": 936, "text": "ning elevated blood pressure and hyperglycemia were core traits of the metabolic syndrome associated with endothelial dysfunction and increased risk of cardiovascular disease. Thus metabol", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26956847", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 826, "text": "abolic syndrome related traits, including waist circumference, systolic blood pressure, glucose, HDL cholesterol, total cholesterol and triglycerides, were measured and adjusted for age and sex. GxEE examin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Metabolic syndrome (MetS), conventionally defined by the presence of at least three out of five dismetabolic traits (abdominal obesity, hypertension, low plasma HDL-cholesterol and high plasma glucose and triglycerides), has been associated with both breast cancer (BC) incidence and prognosis. We inv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26175188", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1357, "text": "T have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of com", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16305067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Metabolic syndrome (MetS), conventionally defined by the presence of at least three out of five dismetabolic traits (abdominal obesity, hypertension, low plasma HDL-cholesterol and high plasma glucose and triglycerides), has been associated with both breast cancer (BC) incidence and prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26175188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Metabolic syndrome (MS), conventionally defined by the presence of at least three out of five dysmetabolic traits (abdominal obesity, hypertension, low plasma HDL-cholesterol, high plasma glucose and high triglycerides), has been associated with an increased risk of several age-related chronic diseases, including breast cancer (BC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25104441", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 402, "text": "Obesity is often associated with the clustering of metabolic and cardiovascular risk factors that contribute to metabolic syndrome or syndrome X. Likewise, metabolic syndrome and its associated traits are major contributing factors to the increase in nephropathy and end stage renal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20021073", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 685, "text": "THODS: We measured personality traits using the Japanese version of the Eysenck Personality Questionnaire (Revised Short Form) and five metabolic syndrome components-elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose-in 1322 participants aged 51.1\u00b112.7years old from Kakegawa city, Japan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29502759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Metabolic syndrome is a cluster of the most dangerous heart attack risk factors (diabetes and raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure), and has become a major global threat to human health.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31637139", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 1026, "text": "Therefore, to demonstrate the utility of both univariate and multivariate family-based association analysis and to identify possible genetic variants associated with metabolic syndrome, we performed a scan of the Affymetrix 50 k Human Gene Panel data using 1) each of the traits comprising metabolic syndrome: triglycerides, high-density lipoprotein, systolic blood pressure, diastolic blood pressure, blood glucose, and body mass index, and 2) a composite trait including all of the above, jointly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20018034", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 664, "text": "ase (CVD). However, the association between personality traits and metabolic syndrome remains controversial, and few studies have been conducted in East Asian populations.METHODS: We measured personality traits using the Japanese version of the Eysenck Personality Questionnaire (Revised Short Form) and five metabolic syndrome components-elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose-in 1322 participants aged 51.1\u00b112.7years old from K", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29502759", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Metabolic syndrome (MetS) is a common complex trait consisting of the clustering of abdominal obesity, hypertension, dyslipidemia, and dysglycemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18489847", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 672, "text": "c syndrome. In an effort to explore the utility of different multivariate methods of data reduction to better understand the genetic influences on the aggregation of metabolic syndrome phenotypes, we calculated phenotypic, genetic, and genome-wide LOD score correlation matrices using five traits (total cholesterol, high density lipoprotein cholesterol, triglycerides, systolic blood pressure, and body mass index) from the Framingham Heart Study data set prepared for the Genetic Analysis Workshop 13, clinic visits 10 and 1 for the original and offspring cohorts, r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14975163", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "PURPOSE: The metabolic syndrome (MS), a cluster of central obesity, dyslipidemia, hyperglycemia, and hypertension, conveys an increased risk of type 2 diabetes and cardiovascular", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17918262", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 630, "text": "Selection for inclusion in Stage 1 was based on four metabolic syndrome component traits: HDL-cholesterol, plasma glucose and Type 2 diabetes, abdominal obesity measured by waist to hip ratio, and diastolic blood pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20694148", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 667, "text": "to insulin. Insulin resistance is associated with a cluster of risk factors recognized as the metabolic syndrome.OBJECTIVE: To describe the epidemiology of the insulin resistance syndrome, also known as the metabolic syndrome.METHODS: Overall obesity, central obesity, dyslipidemia characterized by elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol, hyperglycemia, and hypertension are common traits that, when they occur together, co", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12240700", "endSection": "abstract" } ] }, { "body": "Which gene is responsible for the Liebenberg syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23940102", "http://www.ncbi.nlm.nih.gov/pubmed/30711920", "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "http://www.ncbi.nlm.nih.gov/pubmed/23022097", "http://www.ncbi.nlm.nih.gov/pubmed/23395106", "http://www.ncbi.nlm.nih.gov/pubmed/32598510" ], "ideal_answer": [ "Liebenberg syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. Patients present with prominent neurological, medical, and behavioral symptoms.", "We discuss the genetic abnormality that causes Liebenberg syndrome, the genomic rearrangement at the PITX1 locus on chromosome 5", "We re-define the phenotype of Liebenberg syndrome as a transformation of the upper limbs to reflect lower limb characteristics. We speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds.", "Liebenberg syndrome is caused by genetic changes near the PITX1 gene. The protein produced from this gene plays a critical role in lower limb development by controlling the activity of other genes involved in limb development, directing the shape and structure of bones and other tissues in the legs and feet.", "Liebenberg syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene.", "Liebenberg syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeodomain complex 1 (PITX1) gene.", "Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics The deleted region is upstream to the PITX1 gene.", "Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics" ], "exact_answer": [ "PITX1", "" ], "type": "factoid", "id": "5fdb1023a43ad31278000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "title" }, { "offsetInBeginSection": 484, "offsetInEndSection": 534, "text": "The deleted region is upstream to the PITX1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 997, "text": "We therefore re-define the phenotype of Liebenberg syndrome as a transformation of the upper limbs to reflect lower limb characteristics and speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" }, { "offsetInBeginSection": 514, "offsetInEndSection": 716, "text": "The structural variations seem to result in an ectopic expression of paired-like homeodomain transcription factor 1 (PITX1) in the forelimb causing a partial arm-to-leg transformation in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940102", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 513, "text": "We discuss the genetic abnormality that causes Liebenberg syndrome, the genomic rearrangement at the PITX1 locus on chromosome 5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940102", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1505, "text": "ng CRISPR-Cas9 technology in the mouse and showed that the promoter of the housekeeping gene H2afy insulates the Pen enhancer from Pitx1 in forelimbs; its loss leads to misexpression of Pitx1 by the pan-limb activity of the Pen enhancer causing Liebenberg syndrome.CONCLUSION: Our data indicate that housekeeping promoters may titrate promiscuous enhancer activity to ensure normal morphogenesis. The deletion of the H2AFY pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "title" }, { "offsetInBeginSection": 79, "offsetInEndSection": 401, "text": "Two PITX1-related human disorders have been reported to date: PITX1 ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a \"lower limb\" appearance; PITX1 deletions or missense variation cause a syndromic picture including clubfoot, tibial hemimelia, and preaxial polydactyly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32598510", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 716, "text": "We discuss the genetic abnormality that causes Liebenberg syndrome, the genomic rearrangement at the PITX1 locus on chromosome 5.The structural variations seem to result in an ectopic expression of paired-like homeodomain transcription factor 1 (PITX1) in the forelimb causing a partial arm-to-leg transformation in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940102", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 942, "text": "We generated transgenic mice in which PITX1 was misexpressed under the control of a nearby enhancer and were able to recapitulate the Liebenberg phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23022097", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 436, "text": "allenging. The human Liebenberg syndrome is characterised by a partial transformation of the arms into legs and has been shown to be caused by SVs at the PITX1 locus leading to its misregulation in the forelimb by its native en", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711920", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 406, "text": "wo PITX1-related human disorders have been reported to date: PITX1 ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a \"lower limb\" appearance; PITX1 deletions or missense variation cause a syndromic picture including clubfoot, tibial hemimelia, and preaxial polydactyly. We r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32598510", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 518, "text": "iscuss the genetic abnormality that causes Liebenberg syndrome, the genomic rearrangement at the PITX1 locus on chromosome 5.The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23940102", "endSection": "abstract" }, { "offsetInBeginSection": 767, "offsetInEndSection": 987, "text": "typic overlap is also observed with Ischiocoxopodopatellar syndrome caused by TBX4 haploinsufficiency, and with the phenotypic spectrum caused by SOX9 anomalies, both genes being PITX1 downstream targets. Our study findi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32598510", "endSection": "abstract" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1348, "text": "functionally characterise the variant, we re-engineered the 8.5\u2009kb deletion using CRISPR-Cas9 technology in the mouse and showed that the promoter of the housekeeping gene H2afy insulates the Pen enhancer from Pitx1 in forelimbs; its loss leads to misexpression of Pitx1 by the pan-limb activity of the Pen enhancer causing Liebenberg syndrome.CON", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711920", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 454, "text": " The human Liebenberg syndrome is characterised by a partial transformation of the arms into legs and has been shown to be caused by SVs at the PITX1 locus leading to its misregulation in the forelimb by its native enhancer element Pen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711920", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 725, "text": "The radiological features in the upper limbs of all affected members of the family were almost identical to the phenotype in the mouse model with ectopic expression of Pitx1 in the forelimbs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 533, "text": "The deleted region is upstream to the PITX1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23587911", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 443, "text": "hallenging. The human Liebenberg syndrome is characterised by a partial transformation of the arms into legs and has been shown to be caused by SVs at the PITX1 locus leading to its misregulation in the forelimb by its native enhancer ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711920", "endSection": "abstract" }, { "offsetInBeginSection": 968, "offsetInEndSection": 1434, "text": "rst non-coding exon of H2AFY. To functionally characterise the variant, we re-engineered the 8.5\u2009kb deletion using CRISPR-Cas9 technology in the mouse and showed that the promoter of the housekeeping gene H2afy insulates the Pen enhancer from Pitx1 in forelimbs; its loss leads to misexpression of Pitx1 by the pan-limb activity of the Pen enhancer causing Liebenberg syndrome.CONCLUSION: Our data indicate that housekeeping promoters may titrate promiscuous enhance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30711920", "endSection": "abstract" } ] }, { "body": "Which pharmacogenetic test is recommended prior to administering carbamazepine and why?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27060780" ], "ideal_answer": [ "HLA-B\u221715:02 is known as a biomarker for carbamazepine (CBZ) induced Steven-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) in some Asian populations. Hence United States Federal Drug Administration (USFDA) recommends HLA-B\u221715:02 screening for Asian and other populations with a high prevalence of HLA-B\u221715:02, prior to the administration of carbamazepine." ], "type": "summary", "id": "606ad2ab94d57fd879000053", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "HLA-B\u221715:02 is known as a biomarker for carbamazepine (CBZ) induced Steven-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) in some Asian populations. Hence United States Federal Drug Administration (USFDA) recommends HLA-B\u221715:02 screening for Asian and other populations with a high prevalence of HLA-B\u221715:02, prior to the administration of carbamazepine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27060780", "endSection": "abstract" } ] }, { "body": "Are there sex differences in oncogenic mutational processes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32859912" ], "ideal_answer": [ "Yes. Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. There are sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes.", "Yes. There are sex differences in oncogenic mutational processes." ], "exact_answer": "yes", "type": "yesno", "id": "601fff6a1cb411341a00007b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Sex differences in oncogenic mutational processes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32859912", "endSection": "title" } ] }, { "body": "Which drugs are included in the MAID chemotherapy regimen for sarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7672707", "http://www.ncbi.nlm.nih.gov/pubmed/11300337", "http://www.ncbi.nlm.nih.gov/pubmed/7595717", "http://www.ncbi.nlm.nih.gov/pubmed/2504890", "http://www.ncbi.nlm.nih.gov/pubmed/30032825", "http://www.ncbi.nlm.nih.gov/pubmed/10362334", "http://www.ncbi.nlm.nih.gov/pubmed/9529020", "http://www.ncbi.nlm.nih.gov/pubmed/12478905", "http://www.ncbi.nlm.nih.gov/pubmed/18313854", "http://www.ncbi.nlm.nih.gov/pubmed/31232921", "http://www.ncbi.nlm.nih.gov/pubmed/32881345", "http://www.ncbi.nlm.nih.gov/pubmed/21652583", "http://www.ncbi.nlm.nih.gov/pubmed/2110385", "http://www.ncbi.nlm.nih.gov/pubmed/22179493", "http://www.ncbi.nlm.nih.gov/pubmed/24647783", "http://www.ncbi.nlm.nih.gov/pubmed/2050307", "http://www.ncbi.nlm.nih.gov/pubmed/32427061", "http://www.ncbi.nlm.nih.gov/pubmed/16446334", "http://www.ncbi.nlm.nih.gov/pubmed/12829150", "http://www.ncbi.nlm.nih.gov/pubmed/23092789", "http://www.ncbi.nlm.nih.gov/pubmed/12445253", "http://www.ncbi.nlm.nih.gov/pubmed/8951354" ], "ideal_answer": [ "MAID chemotherapy regimen for sarcomas include mesna, adriamycin, ifosfamide and dacarbazine." ], "exact_answer": [ [ "mesna" ], [ "adriamycin" ], [ "ifosfamide" ], [ "dacarbazine" ] ], "type": "list", "id": "602825a61cb411341a0000fa", "snippets": [ { "offsetInBeginSection": 354, "offsetInEndSection": 496, "text": "Upon completion of 3 cycles of the MAID regimen (mesna, adriamycin, ifosfamide, dacarbazine), computed tomography showed disease progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24647783", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 464, "text": "PATIENTS AND METHODS: Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21652583", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 886, "text": "One randomized trial reported a significant improvement in overall survival for patients receiving doxorubicin and dacarbazine compared to those receiving a combination of doxorubicin, dacarbazine, and ifosfamide (MAID). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18313854", "endSection": "abstract" }, { "offsetInBeginSection": 1199, "offsetInEndSection": 1421, "text": "Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) was the most commonly used chemotherapy regimen as neoadjuvant or adjuvant treatment while ifosfamide (93.7%) was the most commonly used chemotherapy drug in any setting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32881345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Efficacy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in patients with advanced pulmonary pleomorphic carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30032825", "endSection": "title" }, { "offsetInBeginSection": 428, "offsetInEndSection": 685, "text": "MATERIALS AND METHODS: The medical records of 17 patients who received mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for advanced PC between January 2010 and February 2017 were retrospectively analyzed for clinicopathological features and outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30032825", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 413, "text": "A regimen of pre-operative chemotherapy consisting of mesna, adriamycin, ifosfamide and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and post-operative chemotherapy with or without RT, has demonstrated high rates of local and distant control. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23092789", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide, and dacarbazine (MAID) regimen for adult high-grade non-small round cell soft tissue sarcomas", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22179493", "endSection": "title" }, { "offsetInBeginSection": 240, "offsetInEndSection": 442, "text": "Our aim was to investigate the efficacy, feasibility and adverse effects of neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide and dacarbazine (MAID) regimen for NSRCSTSs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22179493", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 472, "text": "The purpose of this clinical trial was to evaluate the efficacy and toxicity of MAID regimen (mesna/ifosfamide + Adriamycin + dacarbazine) in the treatment of advanced soft tissue sarcoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12478905", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 584, "text": "THODS: This Phase II study evaluated doxorubicin, dacarbazine, ifosfamide, and mesna (MAID) in adults with inoperable or metastatic Ewing's sarcoma, rhabdomyosarcoma, or osteosarcoma.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9529020", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 527, "text": "The MAID regimen was administered intravenously every 4 weeks in the hospital as follows: (1) mesna 1500 mg/m2/day x 4 days; (2) doxorubicin 15 mg/m2/day x 3 days; (3) ifosfamide 1500 mg/m2/day x 3 days; (4) dacarbazine 250 mg/m2/day x 3 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12445253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy for gynecological sarcomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12445253", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "PURPOSE: This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7595717", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 454, "text": "e agents at present. The purpose of this clinical trial was to evaluate the efficacy and toxicity of MAID regimen (mesna/ifosfamide + Adriamycin + dacarbazine) in the treatment of advanced so", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12478905", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Startin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2504890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Sta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2504890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) regimen for adults with advanced sarcoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2110385", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2504890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Four patients with metastatic ovarian mixed M\u00fcllerian sarcoma (2 homologous, 2 heterologous) were treated with mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7672707", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 401, "text": " tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12829150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "This study was conducted to determine the maximum tolerated dose of an intensified MAID (mesna, adriamycin, ifosfamide, dacarbazine) regimen with the support of lenograstim in patients with advanced soft tissue sarcomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10362334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 591, "text": "Since dose intensity of doxorubicin is correlated with the clinical response of patients with soft tissue sarcomas and since doxorubicin dose intensity may be compromised in combination chemotherapy, we evaluated the use of recombinant granulocytemacrophage colony-stimulating factor (rGM-CSF) to ameliorate myelosuppression and allow doxorubicin dose escalation in a phase I trial utilizing the MAID combination [Mesna 2.5 g/m2/day x 4 days, Adriamycin (doxorubicin) 15 mg/m2/day x 4 days, ifosfamide 2.0 g/m2/day x 3 days, dacarbazine 250 mg/m2/day x 4 days; to be repeated every 21 days].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8951354", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 586, "text": "She was treated with mesna, ifosfamide, Adriamycin, and dacarbazine (MAID) chemotherapy and after one cycle of chemotherapy she had no evidence of tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2050307", "endSection": "abstract" }, { "offsetInBeginSection": 1106, "offsetInEndSection": 1268, "text": "When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31232921", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 630, "text": "Patients received three cycles of neoadjuvant chemotherapy (CT; modified mesna, doxorubicin, ifosfamide, and dacarbazine [MAID]), interdigitated preoperative radiation therapy (RT; 44 Gy administered in split courses), and three cycles of postoperative CT (modified MAID).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16446334", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 359, "text": "We report, to the best of our knowledge, the first case of myxofibrosarcoma successfully treated with mesna, pirarubicin, ifosfamide and dacarbazine (modified MAID) regimen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32427061", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 436, "text": "The authors report a case of a 57-year-old male with advanced SRCC who had a durable complete response after MAID (mesna, adriamycin, ifosfamide and dacarbazine) chemotherapy, and remains free of disease four years after completing treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11300337", "endSection": "abstract" } ] }, { "body": "Which is the main ligand for the glucocorticoid receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32381682", "http://www.ncbi.nlm.nih.gov/pubmed/32528419", "http://www.ncbi.nlm.nih.gov/pubmed/31995340", "http://www.ncbi.nlm.nih.gov/pubmed/32607951" ], "ideal_answer": [ "Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans)." ], "exact_answer": [ "cortisol" ], "type": "factoid", "id": "606b396994d57fd879000063", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31995340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Glucocorticoids (GCs) act through the glucocorticoid receptor (GR, also known as NR3C1) to regulate immunity, energy metabolism and tissue repair. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32381682", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 622, "text": "Glucocorticoids exert their actions by binding the glucocorticoid receptor (GR) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32528419", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 189, "text": "Generalized glucocorticoid resistance is characterized by impaired cortisol signaling, resulting from mutations in the NR3C1 gene coding the human glucocorticoid receptor (hGR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32607951", "endSection": "abstract" } ] }, { "body": "Who received the Nobel prize for development of CRISPR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33300275", "http://www.ncbi.nlm.nih.gov/pubmed/33201862", "http://www.ncbi.nlm.nih.gov/pubmed/33037027", "http://www.ncbi.nlm.nih.gov/pubmed/33287895" ], "ideal_answer": [ "The 2020 Nobel Prize in Chemistry was awarded to CRISPR-Cas pioneers Emmanuelle Charpentier and Jennifer Doudna. Charpentier and Doudna pioneered the site-specific CRISPR gene-editing technology that has revolutionized cancer research and treatment.", "Emmanuelle Charpentier, PhD, and Jennifer Doudna, PhD, who pioneered the site-specific CRISPR gene-editing technology that has revolutionized cancer research and treatment, were awarded the 2020 Nobel Prize in Chemistry.", "CRISPR has finally won a Nobel Prize. Jennifer Doudna and Emmanuelle Charpentier have been awarded the ultimate science prize for their breakthrough research on CRISPR technology.", "The 2020 Nobel Prize in Chemistry was awarded to CRISPR-Cas pioneers Emmanuelle Charpentier and Jennifer Doudna, who developed the CRISPR-Cas system to precisely edit genomic DNA.", "020 Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer Doudna for their discovery of the CRISPR/Cas9 genetic scissors that have revolutionized genome editing." ], "exact_answer": [ [ "Emmanuelle Charpentier" ], [ "Jennifer Doudna," ] ], "type": "list", "id": "601f19d11cb411341a000073", "snippets": [ { "offsetInBeginSection": 96, "offsetInEndSection": 275, "text": "020 Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer Doudna for their discovery of the CRISPR/Cas9 genetic scissors that have revolutionized genome editing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33201862", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 542, "text": "The 2020 Nobel Prize in Chemistry was awarded to CRISPR-Cas pioneers Emmanuelle Charpentier and Jennifer Doudna, who developed the CRISPR-Cas system to precisely edit genomic DNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Emmanuelle Charpentier, PhD, and Jennifer Doudna, PhD, who pioneered the site-specific CRISPR gene-editing technology that has revolutionized cancer research and treatment, were awarded the 2020 Nobel Prize in Chemistry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33037027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "In October 2020, Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna won the Nobel Prize in Chemistry for their pioneering work in precise genome editing using the CRISPR technology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33287895", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 541, "text": "The 2020 Nobel Prize in Chemistry was awarded to CRISPR-Cas pioneers Emmanuelle Charpentier and Jennifer Doudna, who developed the CRISPR-Cas system to precisely edit genomic DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300275", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 550, "text": "Nobel Prize in Chemistry was awarded to CRISPR-Cas pioneers Emmanuelle Charpentier and Jennifer Doudna, who developed the CRISPR-Cas system to precisely edit genomic DNA. This tec", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Emmanuelle Charpentier, PhD, and Jennifer Doudna, PhD, who pioneered the site-specific CRISPR gene-editing technology that has revolutionized cancer research and treatment, were awarded the 2020 Nobel Prize in Chemistry. Man", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33037027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Katherine Uyhazi and renowned gene therapy pioneer Jean Bennett share their perspective on the 2020 Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer Doudna for their discovery of the CRISPR/Cas9 genetic scissors that have revolutionized genome editing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33201862", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 181, "text": "Jennifer Doudna won the Nobel Prize in Chemistry for their pioneering work in precise genome editing using the CRISPR technology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33287895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Katherine Uyhazi and renowned gene therapy pioneer Jean Bennett share their perspective on the 2020 Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer Doudna for their discovery of the CRISPR/Cas9 genetic scissors that have revolutionized genome editing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33201862", "endSection": "abstract" } ] }, { "body": "How are super enhancers defined?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30078801", "http://www.ncbi.nlm.nih.gov/pubmed/24119843", "http://www.ncbi.nlm.nih.gov/pubmed/26569311", "http://www.ncbi.nlm.nih.gov/pubmed/28991225", "http://www.ncbi.nlm.nih.gov/pubmed/30814546", "http://www.ncbi.nlm.nih.gov/pubmed/26277449", "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "http://www.ncbi.nlm.nih.gov/pubmed/26438538", "http://www.ncbi.nlm.nih.gov/pubmed/25394790", "http://www.ncbi.nlm.nih.gov/pubmed/30541891", "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "http://www.ncbi.nlm.nih.gov/pubmed/30925856", "http://www.ncbi.nlm.nih.gov/pubmed/27677335", "http://www.ncbi.nlm.nih.gov/pubmed/25936917", "http://www.ncbi.nlm.nih.gov/pubmed/29861161", "http://www.ncbi.nlm.nih.gov/pubmed/28034838", "http://www.ncbi.nlm.nih.gov/pubmed/25564661", "http://www.ncbi.nlm.nih.gov/pubmed/26578594", "http://www.ncbi.nlm.nih.gov/pubmed/28373363", "http://www.ncbi.nlm.nih.gov/pubmed/32396464", "http://www.ncbi.nlm.nih.gov/pubmed/31533978", "http://www.ncbi.nlm.nih.gov/pubmed/30371817" ], "ideal_answer": [ "Super-enhancers are defined as genomic regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region.", "Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity.", "Super-enhancers are defined as genomic regions spanned by highly conserved non-coding elements (HCNEs), which include enhancers, transcription factor binding sites that can activate or repress gene expression by multiple mechanisms.", "Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity. Super-enhancers are large clusters of transcriptional enhancers regarded as having essential roles in driving the expression of genes that control cell identity during development and tumorigenesis.", "Super-enhancers (SEs) are large clusters of enhancers that drive expression of genes controlling cell identity. Super-enhancers are important for controlling and defining the expression of cell-specific genes.", "Super enhancers are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as enhancers of one target gene in the region.", "Super-enhancers are defined as genomic regions spanned by highly conserved non-coding elements (HCNEs), which include both syntenic and nonsyntenic regions, that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of many genes, including those encoding major transcription factors.", "The super enhancers are important for defining cell identity in mammalian developmental processes and human diseases. They are defined as genomic regions containing clusters of multiple enhancers, which regulate cell-identity genes and oncogenes. The enhancers can be identified by ChIP sequencing (ChIP-seq) to identify domains enriched for the histone marks histone H3 lysine 4 trimethylation (H3K4me3, H3k4me1, and H3K27ac) and define, for the first time, the super enhancementancers and typical enhancers active in primary human cor", "Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity.", "Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity. They recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac)." ], "type": "summary", "id": "5fdb4112a43ad31278000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30078801", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 263, "text": "called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25394790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28034838", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Super-enhancers are large clusters of transcriptional enhancers regarded as having essential roles in driving the expression of genes that control cell identity during development and tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26578594", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Super-enhancers are important for controlling and defining the expression of cell-specific genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30371817", "endSection": "abstract" }, { "offsetInBeginSection": 1102, "offsetInEndSection": 1256, "text": "Furthermore, we identified a group of 45 subtype-specific super enhancers that are associated with poorer prognosis and are highly dependent on deltaNp63.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30541891", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 516, "text": "Here we report that enhancer RNAs (eRNAs) identified by global nuclear run-on sequencing are extensively transcribed within super enhancers and are dynamically regulated in response to cellular signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25564661", "endSection": "abstract" }, { "offsetInBeginSection": 702, "offsetInEndSection": 863, "text": "Defined as genomic regions containing clusters of multiple enhancers, super enhancers play pivotal roles in cell/tissue specification, identity, and maintenance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28373363", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 315, "text": "Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26569311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Super-enhancers define a proliferative PGC-1\u03b1-expressing melanoma subgroup sensitive to BET inhibition.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28991225", "endSection": "title" }, { "offsetInBeginSection": 428, "offsetInEndSection": 645, "text": "Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27677335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Super-enhancers (SE) have become a popular concept and are widely used as a feature defining key identity genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32396464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Super-enhancers: Asset management in immune cell genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26277449", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Super-enhancers (SEs) are clusters of transcriptional enhancers which control the expression of cell identity and disease-associated genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30814546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage-specific transcription factors driving expression of genes that define cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25936917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28034838", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Super-enhancers are large clusters of enhancers that activate gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29861161", "endSection": "abstract" }, { "offsetInBeginSection": 1084, "offsetInEndSection": 1337, "text": "They are also preferentially bound by the chromatin looping factors CTCF and cohesin, in contrast to super-enhancers, forming clusters of CTCF and cohesin binding regions and defining homotypic clusters of transcription regulator binding regions (HCTs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31533978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Super-enhancers and stretch enhancers represent classes of transcriptional enhancers that have been shown to control the expression of cell identity genes and carry disease- and trait-associated variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1155, "text": "We found that stretch enhancers are more abundant, more distal to transcription start sites, cover twice as much the genome, and are significantly less conserved than super-enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1322, "text": "In contrast, super-enhancers are significantly more enriched for active chromatin marks and cohesin complex, and more transcriptionally active than stretch enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "abstract" }, { "offsetInBeginSection": 1323, "offsetInEndSection": 1534, "text": "Importantly, a vast majority of super-enhancers (85%) overlap with only a small subset of stretch enhancers (13%), which are enriched for cell type-specific biological functions, and control cell identity genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1854, "text": "These results suggest that super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers, and importantly, most of the stretch enhancers that are distinct from super-enhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30169995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Super-enhancers in the control of cell identity and disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119843", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24119843", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 430, "text": "Here we review the identification and composition of super-enhancers, describe links between super-enhancers, gene regulation and disease, and discuss the functional significance of enhancer clustering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1102, "text": "In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 613, "offsetInEndSection": 795, "text": "Our opinion is that there is not yet strong evidence that super-enhancers are a novel paradigm in gene regulation and that use of the term in this context is not currently justified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 612, "text": "We also provide our perspective regarding the proposition that super-enhancers are a regulatory entity conceptually distinct from what was known before the introduction of the term.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "BACKGROUND: Super-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation during development and diff", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30925856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Super-enhancers are clusters of transcriptional enhancers that drive cell-type-specific gene expression and are crucial to cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26438538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26277449", "endSection": "abstract" } ] }, { "body": "Is metoprolol metabolized by CYP2D6?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14732961" ], "ideal_answer": [ "Yes, metoprolol is metabolized by CYP2D6." ], "exact_answer": "yes", "type": "yesno", "id": "606a232a94d57fd87900004c", "snippets": [ { "offsetInBeginSection": 1166, "offsetInEndSection": 1423, "text": "Among these beta-blockers atenolol is mainly eliminated by renal excretion, bisoprolol is in part excreted as parent compound via the renal route (50%), the other 50% are hepatically metabolised, whereas metoprolol and carvedilol are metabolised by CYP2D6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14732961", "endSection": "abstract" } ] }, { "body": "List versions of ExpansionHunter", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31134279", "http://www.ncbi.nlm.nih.gov/pubmed/32345345" ], "ideal_answer": [ "ExpansionHunter and ExpansionHunter Denovo", "ExpansionHunter Denovo is an efficient catalog-free method for genome-wide repeat expansion detection. ExpansionHunter is a sequence-graph-based tool to analyze variation in short tandem repeat regions." ], "exact_answer": [ [ "ExpansionHunter" ], [ "ExpansionHunter Denovo" ] ], "type": "list", "id": "60311f691cb411341a00012a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "ExpansionHunter Denovo: a computational method for locating known and novel repeat expansions in short-read sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32345345", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 723, "text": "Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequencing data require predefined repeat catalogs. Recent discoveries emphasize the need for methods that do not require pre-specified candidate repeats. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide repeat expansion detection. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference repeat expansions not discoverable via existing methods.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32345345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "ExpansionHunter: a sequence-graph-based tool to analyze variation in short tandem repeat regions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31134279", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 786, "text": "We describe a novel computational method for genotyping repeats using sequence graphs. This method addresses the long-standing need to accurately genotype medically important loci containing repeats adjacent to other variants or imperfect DNA repeats such as polyalanine repeats. Here we introduce a new version of our repeat genotyping software, ExpansionHunter, that uses this method to perform targeted genotyping of a broad class of such loci.AVAILABILITY AND IMPLEMENTATION: ExpansionHunter is implemented in C++ and is available under the Apache License Version 2.0. The source code, documentation, and Linux/macOS binaries are available at https://github.com/Illumina/ExpansionHunter/.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31134279", "endSection": "abstract" } ] }, { "body": "What are the uses of Nirsevimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "http://www.ncbi.nlm.nih.gov/pubmed/32759319" ], "ideal_answer": [ "A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants." ], "type": "summary", "id": "6023480b1cb411341a000091", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "title" }, { "offsetInBeginSection": 344, "offsetInEndSection": 611, "text": "METHODS: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" }, { "offsetInBeginSection": 1971, "offsetInEndSection": 2191, "text": "CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 344, "text": "Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" }, { "offsetInBeginSection": 1977, "offsetInEndSection": 2197, "text": "SIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Fund", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" }, { "offsetInBeginSection": 2771, "offsetInEndSection": 2885, "text": "stly, RSV entry and spread were fully inhibited by neutralizing antibodies palivizumab and the novel nirsevimab. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32759319", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 335, "text": "nfants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" }, { "offsetInBeginSection": 1977, "offsetInEndSection": 2196, "text": "SIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Fun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 345, "text": "Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" }, { "offsetInBeginSection": 1845, "offsetInEndSection": 2148, "text": "c locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions.CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32726528", "endSection": "abstract" } ] }, { "body": "What is the proteoglycan Tsukushi?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31027686", "http://www.ncbi.nlm.nih.gov/pubmed/18095058", "http://www.ncbi.nlm.nih.gov/pubmed/16606623" ], "ideal_answer": [ "Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan (SLRP) family, plays multifunctional roles by interacting with signaling molecules during development.\nIn lung cancer cells, TSK is expressed more highly than the other SLRPs family members, and regulates the EMT and proliferation. Thus, TSK may be a key coordinator of multiple pathways and an important structural element in the lung cancer microenvironment.\nGain- and loss-of-function analyses showed that the small leucine-rich proteoglycan, tsukushi, contributes to vitamin K2-mediated enhancement of collagen accumulation." ], "type": "summary", "id": "606b3f4d94d57fd879000066", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 186, "text": "Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan (SLRP) family, plays multifunctional roles by interacting with signaling molecules during development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027686", "endSection": "abstract" }, { "offsetInBeginSection": 1306, "offsetInEndSection": 1563, "text": "In lung cancer cells, TSK is expressed more highly than the other SLRPs family members, and regulates the EMT and proliferation. Thus, TSK may be a key coordinator of multiple pathways and an important structural element in the lung cancer microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31027686", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 730, "text": " small leucine-rich repeat proteoglycan, tsukushi, has been shown to contribute to collagen accumulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18095058", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1085, "text": "Gain- and loss-of-function analyses showed that the small leucine-rich proteoglycan, tsukushi, contributes to vitamin K2-mediated enhancement of collagen accumulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606623", "endSection": "abstract" } ] }, { "body": "Does Curare function by stimulating the acetylcholine receptor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/8355663", "http://www.ncbi.nlm.nih.gov/pubmed/26818254", "http://www.ncbi.nlm.nih.gov/pubmed/4351811", "http://www.ncbi.nlm.nih.gov/pubmed/11849819", "http://www.ncbi.nlm.nih.gov/pubmed/8166227", "http://www.ncbi.nlm.nih.gov/pubmed/2479422", "http://www.ncbi.nlm.nih.gov/pubmed/21422738", "http://www.ncbi.nlm.nih.gov/pubmed/6283380", "http://www.ncbi.nlm.nih.gov/pubmed/2713760", "http://www.ncbi.nlm.nih.gov/pubmed/25409503", "http://www.ncbi.nlm.nih.gov/pubmed/12624651", "http://www.ncbi.nlm.nih.gov/pubmed/6308151", "http://www.ncbi.nlm.nih.gov/pubmed/16083", "http://www.ncbi.nlm.nih.gov/pubmed/10934261", "http://www.ncbi.nlm.nih.gov/pubmed/22194270" ], "ideal_answer": [ "No. Curare function does not stimulate the acetylcholine receptor.", "Usual clinical concentrations of curare cause competitive inhibition of muscle nicotinic acetylcholine receptors.", "No, curare is an inhibitor of acetylcholine-induced currents that only blocks the N-terminal glutamine-rich channel.", "No, curare is an antagonist of acetylcholine-induced currents that binds to the choline receptor." ], "exact_answer": "no", "type": "yesno", "id": "60292e1b1cb411341a000111", "snippets": [ { "offsetInBeginSection": 1558, "offsetInEndSection": 1732, "text": "Usual clinical concentrations of curare cause competitive inhibition of muscle nicotinic acetylcholine receptors while higher concentrations may induce open channel blockade.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11849819", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 364, "text": "nicotinic acetylcholine receptor (nAChR)-blocking agents [e.g., curare or alpha-bungarotoxin (alpha-BTX)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10934261", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 403, "text": "The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21422738", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 996, "text": "Both EFS- and carbachol-evoked contractions of the UES were blocked by curare at a lower concentration than by atropine or hexamethonium, suggesting that the acetylcholine receptor is nicotinic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12624651", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 860, "text": "We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26818254", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 411, "text": "The EFS-induced contraction of the UES was completely blocked by tetrodotoxin and curare, and abolished in Ca2+ -free Ringer solution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12624651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Curare binding and the curare-induced subconductance state of the acetylcholine receptor channel.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2479422", "endSection": "title" }, { "offsetInBeginSection": 705, "offsetInEndSection": 860, "text": "We have further investigated this particular mutation by examining the interaction of the competitive antagonist d-tubocurarine (curare) with the receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8355663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "d-Tubocurarine (curare) is a well-characterized competitive antagonist of nicotinic acetylcholine receptors (AChRs), and it is usually assumed that curare and agonists share a common binding site.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8166227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Curare action on nicotinic acetylcholine receptors has a number of facets, of which the best known is competitive antagonism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2713760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The mode of action of curare, a well-known competitive antagonist of acetylcholine at the nicotinic receptor, was examined with the single channel recording technique. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6308151", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 444, "text": "ently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref. 6). U", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6283380", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1101, "text": "One site, competitively blocked by bungarotoxin and by curare, is presumably the acetylcholine receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4351811", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 938, "text": "In neuromuscular junction (NMJ) preparations, movements of the muscle must be inhibited if imaging during stimulation is desired (e.g., by application of curare, a potent acetylcholine receptor inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22194270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Curare has long been regarded as a typical competitive antagonist of acetylcholine (ACh) at the vertebrate neuromuscular junction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6283380", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 527, "text": "Curare inhibition of wild-type receptors is consistent with curare binding to a single high-affinity binding site [inhibitor constant (Ki) = 20 nM].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8166227", "endSection": "abstract" }, { "offsetInBeginSection": 763, "offsetInEndSection": 1132, "text": "Phenylalanine substitution for alpha Y198 [alpha Y198F (notation used here: subunit/amino acid in wild-type/residue number/substitution)] causes a 10-fold increase in curare affinity (Ki = 3.1 nM), and measurement of the recovery from curare inhibition indicates that this increase in affinity is due to a reduction in the rate of curare dissociation from the receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8166227", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1225, "text": "rthermore, sudden increases of research activity are ascribable to historic events, like the first use of curare as muscle relaxant during surgery.DIS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25409503", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 438, "text": "Recently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6283380", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1390, "text": "In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The mode of action of curare, a well-known competitive antagonist of acetylcholine at the nicotinic receptor, was examined with the single channel recording technique.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6308151", "endSection": "abstract" } ] }, { "body": "Are somatic mutations positioned towards the nuclear periphery?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11243810", "http://www.ncbi.nlm.nih.gov/pubmed/28967881", "http://www.ncbi.nlm.nih.gov/pubmed/15494683" ], "ideal_answer": [ "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery.", "Yes, somatic mutations are more preferentially located at the nuclear periphery than at the core.", "Yes, somatic mutations are preferentially located in the lamina-associated regions of the genome.", "Yes, somatic mutations are more preferentially situated at the nuclear periphery.", "We found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nucle core. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nucle periphery. At day 4, GOF, its carrier chromosome territory 13 and the non-carrier homolog had moved back toward the nucleus.", "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery.", "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core.", "Yes, somatic mutations are more preferentially located in the nuclear periphery than in the core.", "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes.", "Mutational signatures differ between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery.", "Lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery.", "Lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nucle core. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, are more enriched in the nucle periphery. The distribution of retrogenes in the Drosophila melanogaster genome can be explained by an insertion bias toward chromosome domains containing testis-biased genes that are located at the nucleus in somatic cells.", "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery.", "Yes, somatic mutations are preferentially located in the chromatin near the nuclear periphery." ], "exact_answer": "yes", "type": "yesno", "id": "5fdb2ee4a43ad3127800000f", "snippets": [ { "offsetInBeginSection": 254, "offsetInEndSection": 436, "text": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967881", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 860, "text": "Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967881", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 436, "text": "We found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967881", "endSection": "abstract" }, { "offsetInBeginSection": 243, "offsetInEndSection": 440, "text": "found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28967881", "endSection": "abstract" } ] }, { "body": "Which biological drugs are EMA approved for pediatric psoriasis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31514420" ], "ideal_answer": [ "Currently there are three European Medicines Agency (EMA)-approved biological treatment options for pediatric psoriasis: etanercept, ustekinumab, and adalimumab." ], "exact_answer": [ [ "etanercept" ], [ "ustekinumab" ], [ "adalimumab" ] ], "type": "list", "id": "606b6dc194d57fd87900006a", "snippets": [ { "offsetInBeginSection": 664, "offsetInEndSection": 826, "text": "Currently there are three European Medicines Agency (EMA)-approved biological treatment options for pediatric psoriasis: etanercept, ustekinumab, and adalimumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31514420", "endSection": "abstract" } ] }, { "body": "What is the role of Adamts18 in hormone receptor signaling?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32218432" ], "ideal_answer": [ "Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation.", "The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts with the basal membrane-specific proteoglycan, Col18a1.", "Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. Both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche. In vitro, ADAMTS18 cleaves fibronectin; in vivo, Adamts18 deletion causes increased collagen deposition during puberty, which results in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell function. Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation.", "Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche.", "In vitro, ADAMTS18 cleaves fibronectin; in vivo, it causes increased collagen deposition during adolescence, which results in impaired Hippo signaling and reduced Fgfr2 expression both in vitro and in vivo. Importantly, it is required for stem cell activation, has multiple binding partners in the basement membrane, and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the caveolae of stem cells as part of the stem cell niche." ], "type": "summary", "id": "60290f741cb411341a00010b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32218432", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1061, "text": "Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important to breast physiology and tumorigenesis, remains unclear. Here we report that both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche. In vitro, ADAMTS18 cleaves fibronectin; in vivo, Adamts18 deletion causes increased collagen deposition during puberty, which results in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell function. Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32218432", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1061, "text": "Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32218432", "endSection": "abstract" } ] }, { "body": "Is belimumab effective for the lupus nephritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24014569", "http://www.ncbi.nlm.nih.gov/pubmed/32537456", "http://www.ncbi.nlm.nih.gov/pubmed/33186226", "http://www.ncbi.nlm.nih.gov/pubmed/32755035", "http://www.ncbi.nlm.nih.gov/pubmed/32591783", "http://www.ncbi.nlm.nih.gov/pubmed/29514612", "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "http://www.ncbi.nlm.nih.gov/pubmed/26712500", "http://www.ncbi.nlm.nih.gov/pubmed/32937045" ], "ideal_answer": [ "Yes, belimumab appears to effective for the lupus nephritis." ], "exact_answer": "yes", "type": "yesno", "id": "6020ab801cb411341a000081", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32591783", "endSection": "title" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1747, "text": "CONCLUSIONS: Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32591783", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Clinical Efficacy of Routinely Administered Belimumab on Proteinuria and Neuropsychiatric Lupus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32537456", "endSection": "title" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 1765, "text": "Conclusions: In our series, BEL led to a decrease of proteinuria in patients with proteinuria of more than 1,000 mg/g creatinine despite standard of care treatment, and led to a marked clinical improvement in one patient with NPSLE. No adverse events were observed. Routinely administered BEL shows clinical efficacy on non-approved manifestations, but careful patient selection is warranted.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32537456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755035", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVE: To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755035", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1803, "text": "CONCLUSION: The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755035", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 657, "text": "RECENT FINDINGS: Recently, the Belimumab in Subjects with Systemic Lupus Erythematosus - Lupus Nephritis trial tested belimumab, an inhibitor of B-cell activating factor, as an add-on therapy to steroids and either mycophenolate mofetil (MMF) or cyclophosphamide when given IV monthly over a period of 104 weeks at an effect size of 11% for a Primary Efficacy Renal Response. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Case report: successful treatment of membranous lupus nephritis with belimumab in an African female immigrant.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26712500", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Successful treatment of a mycophenolate mofetil-refractory proliferative lupus nephritis with Belimumab in a 19-year-old woman.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24014569", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 516, "text": "Following treatment with belimumab, proteinuria rapidly improved to almost normal levels and clinical remission lasted. Belimumab might hold promise for this indication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24014569", "endSection": "abstract" } ] }, { "body": "Which are the lactate isomers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32365804", "http://www.ncbi.nlm.nih.gov/pubmed/27119568", "http://www.ncbi.nlm.nih.gov/pubmed/29501496" ], "ideal_answer": [ "Lactate contains a chiral carbon and thus has two optical isomers-d-lactate and l-lactate." ], "exact_answer": [ [ "d-lactate" ], [ "l-lactate" ] ], "type": "list", "id": "606b295294d57fd87900005b", "snippets": [ { "offsetInBeginSection": 597, "offsetInEndSection": 656, "text": "D(-) and L(+) lactate isomers produced by Lactobacillus spp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32365804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Lactate contains a chiral carbon and thus has two optical isomers-d-lactate and l-lactate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Mucosal cells of the gastrointestinal and female reproductive tract are constantly exposed to l- and d-lactate of bacterial origin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27119568", "endSection": "abstract" } ] }, { "body": "What is the function of the Eyeless associated gene in Drosophila?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11536287", "http://www.ncbi.nlm.nih.gov/pubmed/10198632", "http://www.ncbi.nlm.nih.gov/pubmed/9159393", "http://www.ncbi.nlm.nih.gov/pubmed/15253940", "http://www.ncbi.nlm.nih.gov/pubmed/11804780", "http://www.ncbi.nlm.nih.gov/pubmed/30706848", "http://www.ncbi.nlm.nih.gov/pubmed/11335113", "http://www.ncbi.nlm.nih.gov/pubmed/10357938", "http://www.ncbi.nlm.nih.gov/pubmed/11153010", "http://www.ncbi.nlm.nih.gov/pubmed/28993201", "http://www.ncbi.nlm.nih.gov/pubmed/11861484", "http://www.ncbi.nlm.nih.gov/pubmed/19527703", "http://www.ncbi.nlm.nih.gov/pubmed/9892673", "http://www.ncbi.nlm.nih.gov/pubmed/12654291", "http://www.ncbi.nlm.nih.gov/pubmed/24009524", "http://www.ncbi.nlm.nih.gov/pubmed/21208993", "http://www.ncbi.nlm.nih.gov/pubmed/11735383", "http://www.ncbi.nlm.nih.gov/pubmed/11445545", "http://www.ncbi.nlm.nih.gov/pubmed/11842182", "http://www.ncbi.nlm.nih.gov/pubmed/19666017", "http://www.ncbi.nlm.nih.gov/pubmed/19406113", "http://www.ncbi.nlm.nih.gov/pubmed/30295802", "http://www.ncbi.nlm.nih.gov/pubmed/9177348", "http://www.ncbi.nlm.nih.gov/pubmed/9428513", "http://www.ncbi.nlm.nih.gov/pubmed/7892602", "http://www.ncbi.nlm.nih.gov/pubmed/11685574", "http://www.ncbi.nlm.nih.gov/pubmed/16879729" ], "ideal_answer": [ "Eyeless (ey) also known as Pax6, is one of the most critical transcription factors for initiating the entire eye development in Drosophila.", "Theeye-associated Pax6 gene controls neuronal navigation in Drosophila.", "Eyeless (ey) is one of the most critical transcription factors for initiating the entire eye development in Drosophila. Two Pax6 genes are in Drosophila: eyeless (ey) and twin of eyeless (toy)", "Eyeless (ey) is one of the most critical transcription factors for initiating the entire eye development in Drosophila." ], "exact_answer": [ "transcription factor", "transcriptional regulator", "eye development" ], "type": "factoid", "id": "6068640894d57fd87900004b", "snippets": [ { "offsetInBeginSection": 394, "offsetInEndSection": 538, "text": "Moreover, we found that the temporal transcription factor (TTF) Eyeless/Pax6 regulates the development of two recurrently-connected CX subtypes:", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30706848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Eyeless (ey) is one of the most critical transcription factors for initiating the entire eye development in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30295802", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 294, "text": "ax6 transcription factors are essential upstream regulators in the developing anterior brain and peripheral visual system of most bilaterian animals. While a single homolog is in charge of these functions in vertebrates, two Pax6 genes are in Drosophila: eyeless (ey) and twin of eyeless (toy)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28993201", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 477, "text": " Eye development in the fruit fly Drosophila melanogaster is driven by the highly conserved selector gene network referred to as the \"retinal determination gene network,\" composed of approximately 20 factors, whose core comprises twin of eyeless (toy), eyeless (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24009524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Mutational analysis of the eyeless gene and phenotypic rescue reveal that an intact Eyeless protein is necessary for normal eye and brain development in Drosophila.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666017", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "Loss of Pax 6 function leads to an eyeless phenotype in both mammals and insects, and ectopic expression of both the Drosophila and the mouse gene leads to the induction of ectopic eyes in Drosophila, which suggested to us that Pax 6 might be a universal master control gene for eye morphogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11842182", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1234, "text": "These data, along with the phenotypes observed in the four newly characterized eyeless alleles, demonstrate the requirement for an intact Eyeless protein for normal Drosophila eye and brain development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19666017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "The Pax6 genes eyeless (ey) and twin of eyeless (toy) are upstream regulators in the retinal determination gene network (RDGN), which instructs the formation of the adult eye primordium in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19527703", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 293, "text": "In Drosophila, two Pax6 genes function in a pathway in which twin of eyeless (toy) directly regulates eyeless (ey), which is necessary for initiating the eye developmental pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15253940", "endSection": "abstract" }, { "offsetInBeginSection": 712, "offsetInEndSection": 901, "text": "this, we present evidence that eyeless (ey), which encodes the Drosophila homolog of Pax-6, directly regulates rhodopsin 1 (rh1) expression in the photoreceptor cells. We detect ey expressi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9159393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "The Drosophila compound eye is specified by the simultaneous and interdependent activity of transcriptional regulatory genes from four families: PAX6 (eyeless, twin of eyeless, eyegone), EYA (eyes absent), SIX (sine oculis, Optix) and DACH (dachshund). Mammals hav", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11735383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "We describe here the role of the transcription factors encoding genes tailless (tll), atonal (ato), sine oculis (so), eyeless (ey) and eyes absent (eya), and EGFR signaling in establishing the Drosophila embryonic visual system. The embryon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10357938", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The eyeless, dachshund, and eyes absent genes encode conserved, nuclear proteins that are essential for eye development in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9428513", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 662, "text": "The Drosophila homologue of Pax6, eyeless, is also necessary for correct invertebrate eye development, and its misexpression leads to formation of ectopic eyes in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9177348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Differential expression and function of the Drosophila Pax6 genes eyeless and twin of eyeless in embryonic central nervous system development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11335113", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "The eyeless homeodomain is dispensable for eye development in Drosophila.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11445545", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "eyeless (ey) is a key regulator of the eye development pathway in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12654291", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 577, "text": "Previous work has demonstrated the existence of a functional network and genetic regulatory hierarchy in Drosophila in which eyeless (ey, the Pax6 orthologue), eyes absent (eya), and dac operate together to regulate Drosophila eye development, and that ey regulates the expression of eya and dac.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11804780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Drosophila Pax-6/eyeless is essential for normal adult brain structure and function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153010", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 359, "text": "A combination of bioinformatics, comparative expression profiling and microarray-based epistasis experiments has recently identified new targets of Eyeless, a key transcription factor in Drosophila retinal determination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16879729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "In 1995, the eyeless (ey) gene was dubbed the \"master-regulator\" of eye development in Drosophila.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11536287", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 640, "text": "eyeless, which encodes a Pax6 transcription factor, is expressed early in progenitors and controls aspects of this cell migration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21208993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The Drosophila gene eyeless (ey) encodes a transcription factor with both a paired domain and a homeodomain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7892602", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Eye specification in Drosophila is thought be controlled by a set of seven nuclear factors that includes the Pax6 homolog, Eyeless.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11685574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "A role for the Pax-6 homologue eyeless in adult Drosophila brain development and function is described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11153010", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 1009, "text": "We show that several binding sites are required for the eye specific expression, and, therefore, we propose a Pax-6-like molecule to be a positive transactivator for the eye specific ey expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9892673", "endSection": "abstract" }, { "offsetInBeginSection": 379, "offsetInEndSection": 472, "text": "In Drosophila eyeless and twin of eyeless, play non-redundant roles in the developing retina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19406113", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 229, "text": "Members of one subclass, Pax6, function as selector genes and play key roles in the retinal development of all seeing animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19406113", "endSection": "abstract" }, { "offsetInBeginSection": 1367, "offsetInEndSection": 1549, "text": "The identification of both transcriptional activator and repressor activity within the Pax6 protein furthers our understanding of how this gene family regulates tissue determination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19406113", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 834, "text": "eyeless induces much larger ectopic eyes, at higher frequencies, and in a broader range of tissues than twin of eyeless.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19406113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Pax genes encode DNA binding proteins that play pivotal roles in the determination of complex tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19406113", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "The Drosophila Pax-6 gene eyeless (ey) plays a key role in eye development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10198632", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The two Pax6 gene homologs eyeless and twin of eyeless play decisive early roles in Drosophila eye development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11861484", "endSection": "abstract" } ] }, { "body": "Are enhancers directional in their targeting of gene promoters?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15198202", "http://www.ncbi.nlm.nih.gov/pubmed/10550664" ], "ideal_answer": [ "Promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously. Most enhancers are able to regulate promoters on either side.", "These promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously.", "Bi-directional duplex promoters (BDDP) were constructed by placing two identical core promoters divergently on both upstream and downstream sides of their duplicated enhancer elements. These promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously." ], "exact_answer": "no", "type": "yesno", "id": "5fdb4311a43ad31278000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Novel bi-directional duplex promoters (BDDP) were constructed by placing two identical core promoters divergently on both upstream and downstream sides of their duplicated enhancer elements.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15198202", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 567, "text": "These promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10550664", "endSection": "abstract" } ] }, { "body": "Has dupilumab been FDA approved for atopic dermatitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31603635", "http://www.ncbi.nlm.nih.gov/pubmed/32344789", "http://www.ncbi.nlm.nih.gov/pubmed/32439390", "http://www.ncbi.nlm.nih.gov/pubmed/31364023", "http://www.ncbi.nlm.nih.gov/pubmed/30785362" ], "ideal_answer": [ "Yes, dupilumab has been approved by FDA for atopic dermatitis." ], "exact_answer": "yes", "type": "yesno", "id": "606b718994d57fd87900006b", "snippets": [ { "offsetInBeginSection": 315, "offsetInEndSection": 575, "text": "Recent advances and understanding of the pathogenesis of AD have resulted in new therapies that target specific pathways with increased efficacy and the potential for less systemic side effects. New FDA-approved therapies for AD are crisaborole and dupilumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31364023", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 510, "text": "In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30785362", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Dupilumab is the first US FDA approved biologic for treatment of atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32439390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32344789", "endSection": "abstract" } ] }, { "body": "Describe ReactomeGSA", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32907876" ], "ideal_answer": [ "ReactiveomeGSA is a novel resource for comparative pathway analyses of multi-omics datasets. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAt Atlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. reactomegSA greatly reduces the technical barrier for multi-CSF, cross-species, and Comparative Pathways analysis.", "Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge. ReactomeGSA performs comparative pathway analyses of multi-omics datasets. It can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.", "ReactiveomeGSA is a novel R Bioconductor package for comparative pathway analyses of multi-omics datasets. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAt Atlas can be directly integrated in the analysis. ReactomeGsa greatly reduces the technical barrier for multi-seq, cross-species, comparative pathway analysis.", "Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge. ReactomeGSA is a resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.", "ReactomeGSA is a new pathway analysis tool integrated into the Reactome ecosystem. Its main feature is that it performs quantitative pathway analyses (so-called gene set analyses). This increases the statistical power of the differential expression analysis, which is directly performed on the pathway level.", "ReactiveomeGSA is a novel resource for comparative pathway analyses of multi-omics datasets." ], "type": "summary", "id": "6060732b94d57fd87900003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 766, "text": "Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge.Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1419, "text": "Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge.Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.We used ReactomeGSA to characterize the role of B cells in anti-tumor immunity. We compared B cell rich and poor human cancer samples from five of the Cancer Genome Atlas (TCGA) transcriptomics and two of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteomics studies. B cell-rich lung adenocarcinoma samples lacked the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumor associated IgG+ plasma cells that lack NFkappaB activation in scRNA-seq data from human melanoma. This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 845, "text": "ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.We used ReactomeGSA to characterize the role of B cells in anti-tumor immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "abstract" }, { "offsetInBeginSection": 1309, "offsetInEndSection": 1419, "text": "This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "title" }, { "offsetInBeginSection": 310, "offsetInEndSection": 466, "text": "ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "abstract" }, { "offsetInBeginSection": 64, "offsetInEndSection": 309, "text": "Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge.Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32907876", "endSection": "abstract" } ] }, { "body": "What is the role of phenylbutyrate\u2013taurursodiol for amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33063909", "http://www.ncbi.nlm.nih.gov/pubmed/32877582" ], "ideal_answer": [ "Treatment of amyotrophic lateral sclerosis patients with phenylbutyrate\u2013taurursodiol was associated with both functional and survival benefits." ], "type": "summary", "id": "6020b43a1cb411341a000087", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063909", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063909", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1288, "text": "Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32877582", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 635, "text": "METHODS: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32877582", "endSection": "abstract" }, { "offsetInBeginSection": 1759, "offsetInEndSection": 2128, "text": "CONCLUSIONS: Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32877582", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Her", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33063909", "endSection": "abstract" }, { "offsetInBeginSection": 1765, "offsetInEndSection": 1923, "text": "SIONS: Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Seco", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32877582", "endSection": "abstract" } ] }, { "body": "What is known about growth arrest-specific 6 protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32969596", "http://www.ncbi.nlm.nih.gov/pubmed/31583710", "http://www.ncbi.nlm.nih.gov/pubmed/30346880" ], "ideal_answer": [ "Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Recent studies indicate that Gas6 and receptors of the TAM (Tyro3, Axl, and Mer) family may be involved in the pathogenesis of obesity, systemic inflammation, and insulin resistance." ], "type": "summary", "id": "606b33e394d57fd879000061", "snippets": [ { "offsetInBeginSection": 120, "offsetInEndSection": 348, "text": "Growth arrest-specific\u00a06 (GAS6) is a gene encoding the Gas6 protein, which is expressed in fibroblasts, and its related signaling might be associated with adipose tissue inflammation, glucose intolerance and insulin resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32969596", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 351, "text": " Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Recent studies indicate that Gas6 and receptors of the TAM (Tyro3, Axl, and Mer) family may be involved in the pathogenesis of obesity, systemic inflammation, and insulin resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Gamma-glutamyl-carboxylated Gas6 mediates positive role of vitamin K on lowering hyperglycemia in type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31583710", "endSection": "title" } ] }, { "body": "What is Leptomeningeal disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28802798" ], "ideal_answer": [ "Neoplastic leptomeningeal disease (LMD) represents infiltration of the leptomeninges by tumor cells.", "Neoplastic leptomeningeal disease (LMD) represents infiltration of the leptomeninges by tumor cells. LMD represents infiltration of the leptomeninges by tumor cells." ], "type": "summary", "id": "5e57fb40b761aafe09000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Neoplastic leptomeningeal disease (LMD) represents infiltration of the leptomeninges by tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28802798", "endSection": "abstract" } ] }, { "body": "What percent of Rheumatoid Arthritis (RA) patients are not responding to anti-TNF therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16705046", "http://www.ncbi.nlm.nih.gov/pubmed/19211043", "http://www.ncbi.nlm.nih.gov/pubmed/18713756", "http://www.ncbi.nlm.nih.gov/pubmed/17354663", "http://www.ncbi.nlm.nih.gov/pubmed/27974105", "http://www.ncbi.nlm.nih.gov/pubmed/20444755", "http://www.ncbi.nlm.nih.gov/pubmed/17985409", "http://www.ncbi.nlm.nih.gov/pubmed/19389230", "http://www.ncbi.nlm.nih.gov/pubmed/25504080", "http://www.ncbi.nlm.nih.gov/pubmed/22133052", "http://www.ncbi.nlm.nih.gov/pubmed/25733803", "http://www.ncbi.nlm.nih.gov/pubmed/21431944" ], "ideal_answer": [ "These therapies are, however, expensive and 30% of patients fail to respond.", "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response.", "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with RA, showing beneficial effects in approximately 25% of the patients.", "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. By contrast, those patients who had failed to respond to 2 or more anti-TNF agents had a 72.5% lower probability of achieving a moderate to good EULAR response.", "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond", "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond." ], "exact_answer": [ "30%" ], "type": "factoid", "id": "5fe31307a43ad3127800003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18713756", "endSection": "abstract" }, { "offsetInBeginSection": 1765, "offsetInEndSection": 1924, "text": "By contrast, those patients who had failed to respond to 2 or more anti-TNF agents had a 72.5% lower probability of achieving a moderate to good EULAR response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22133052", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1216, "text": "A 12-month EULAR non-response was observed in 153/821 (18.6%) associated with a higher baseline HAQ score (AOR 1.51, 95% CI 1.03-2.20, p: 0.033), prior treatment with >3 DMARDs (AOR 1.76, 95% CI 1.09-2.85; p: 0.021) and corticosteroid >5 mg/day (AOR 2.05, 95% CI 1.06-3.97; p: 0.034)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19211043", "endSection": "abstract" }, { "offsetInBeginSection": 1229, "offsetInEndSection": 1368, "text": "We found that only a minority of patients with long-standing RA treated with anti-TNF agents achieve a good clinical response or remission.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19211043", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1097, "text": "Agreement between responses was substantial at the overall/ACR20 level (about 95%, kappa = 0.7 or better) for all criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19389230", "endSection": "abstract" }, { "offsetInBeginSection": 1514, "offsetInEndSection": 1639, "text": "After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16705046", "endSection": "abstract" }, { "offsetInBeginSection": 1519, "offsetInEndSection": 1834, "text": "Anti-TNF treatments are effective and safe, reducing the activity of the disease, disability, and the need for corticosteroids. Patients who displayed good adherence prior to the anti-TNF treatment and were treated with etanercept or with increasing doses of infliximab had the best chance of displaying a response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17985409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: Anti-tumour necrosis factor (anti-TNF) therapy has proved to be highly successful in treating rheumatoid arthritis (RA), although 30-40% of patients have little or no r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20444755", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Although anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), survival rates and resistance-to-therapy data confirm that about 30% of RA patients fail to respond. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25733803", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 177, "text": "However, 20-30% of patients do not respond sufficiently to a given anti-TNF drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17354663", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 195, "text": "These therapies are, however, expensive and 30% of patients fail to respond.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18713756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "UNLABELLED: Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TN", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25504080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Although TNF inhibitors have dramatically improved the outcome of patients with rheumatoid arthritis, 30-40% of patients do not respond well to them and treatment needs to be changed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21431944", "endSection": "abstract" } ] }, { "body": "Which recombinant antibody therapeutics were granted marketing approval in 2014?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25484055" ], "ideal_answer": [ "Six recombinant antibody therapeutics (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted their first marketing approvals in 2014." ], "exact_answer": [ [ "vedolizumab" ], [ "siltuximab" ], [ "ramucirumab" ], [ "pembrolizumab" ], [ "nivolumab" ], [ "blinatumomab" ] ], "type": "list", "id": "606b767294d57fd87900006d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25484055", "endSection": "abstract" } ] }, { "body": "What is caused by BACH2-related immunodeficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28530713" ], "ideal_answer": [ "Affected subjects of a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. The mutations disrupted protein stability by interfering with homodimerization or by causing aggregation." ], "exact_answer": [ [ "immunoglobulin deficiency" ], [ "intestinal inflammation" ] ], "type": "list", "id": "6027fec01cb411341a0000f0", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1284, "text": "The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. The mutations disrupted protein stability by interfering with homodimerization or by causing aggregation. We observed analogous lymphocyte defects in Bach2-heterozygous mice. More generally, we observed that genes that cause monogenic haploinsufficient diseases were substantially enriched for TFs and SE architecture. These findings reveal a previously unrecognized feature of SE architecture in Mendelian diseases of immunity: heterozygous mutations in SE-regulated genes identified by whole-exome/genome sequencing may have greater significance than previously recognized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28530713", "endSection": "abstract" } ] }, { "body": "Should cerebrolysin be used for aneurysmal subarachnoid hemorrhage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33143640", "http://www.ncbi.nlm.nih.gov/pubmed/30414051" ], "ideal_answer": [ "No. Randomized clinical trial did not find any superior effects of cerebrolysin for patients with aneurysmal subarachnoid hemorrhage." ], "exact_answer": "no", "type": "yesno", "id": "6025dd0c1cb411341a0000b9", "snippets": [ { "offsetInBeginSection": 1061, "offsetInEndSection": 1810, "text": "No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79-15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28-2.59).CONCLUSIONS: Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33143640", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1435, "text": "CONCLUSION: Cerebrolysin injection during the acute period of SAH appeared to reduce the mortality rate, especially in poor-grade patients. This study suggests the potential of Cerebrolysin for treating aneurysmal SAH. Further studies are needed to confirm our results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30414051", "endSection": "abstract" } ] }, { "body": "Do bacteria release extracellular vesicles?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33264437", "http://www.ncbi.nlm.nih.gov/pubmed/31633842", "http://www.ncbi.nlm.nih.gov/pubmed/31776460" ], "ideal_answer": [ "Yes, Bacterial extracellular vesicles (EVs) are bilayered lipid membrane structures, bearing integral proteins and able to carry diverse cargo outside the cell to distant sites." ], "exact_answer": "yes", "type": "yesno", "id": "603213ea1cb411341a000131", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Bacterial extracellular vesicles (EVs) are bilayered lipid membrane structures, bearing integral proteins and able to carry diverse cargo outside the cell to distant sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31633842", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 287, "text": "Knowledge of the structure, molecular cargo and function of bacterial extracellular vesicles (BEVs) is primarily obtained from bacteria cultured in laboratory conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776460", "endSection": "abstract" }, { "offsetInBeginSection": 367, "offsetInEndSection": 406, "text": "bacteria derived-extracellular vesicles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33264437", "endSection": "abstract" } ] }, { "body": "What is the effect of the venom of the cone snail, Conus tulipa?", "_type": "summary", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31780714", "http://www.ncbi.nlm.nih.gov/pubmed/30747102", "http://www.ncbi.nlm.nih.gov/pubmed/2180939", "http://www.ncbi.nlm.nih.gov/pubmed/12824165", "http://www.ncbi.nlm.nih.gov/pubmed/30669642", "http://www.ncbi.nlm.nih.gov/pubmed/25605914", "http://www.ncbi.nlm.nih.gov/pubmed/12507705", "http://www.ncbi.nlm.nih.gov/pubmed/9080592" ], "_body": "What is the effect of the venom of the cone snail, Conus tulip?", "ideal_answer": [ "Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating \u03b1-, \u03c9-, \u03bc-, \u03b4-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins.", "Conus tulipa venom comprised both paralytic (putative ion channel modulating \u03b1-, \u03c9-, \u03bc-, \u03b4-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins." ], "type": "summary", "id": "604f632494d57fd879000007", "snippets": [ { "offsetInBeginSection": 899, "offsetInEndSection": 1069, "text": "Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating \u03b1-, \u03c9-, \u03bc-, \u03b4-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30669642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25605914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30747102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Conantokin-T, a 21-amino acid peptide which induces sleep-like symptoms in young mice was purified from the venom of the fish-hunting cone snail, Conus tulipa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2180939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "This study investigated the mode of action of conantokin-T, a 21 amino acid peptide toxin isolated from the venom of the fish-hunting cone snail Conus tulipa, on excitatory synaptic transmission in rat hippocampal slices using intracellular recording techniques. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9080592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Conantokin-T, a 21-amino acid peptide which induces sleep-like symptoms in young mice was purified from the venom of the fish-hunting cone snail, Conus tulipa. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2180939", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1068, "text": "Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating \u03b1-, \u03c9-, \u03bc-, \u03b4-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30669642", "endSection": "abstract" }, { "offsetInBeginSection": 1069, "offsetInEndSection": 1195, "text": "This venomic study confirms the potential for non-paralytic conotoxins to contribute to the net-hunting strategy of C. tulipa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30669642", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 990, "text": "Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating \u03b1-, \u03c9-, \u03bc-,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30669642", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 860, "text": "Surprisingly, the conantokins (NMDA receptor antagonists) and/or conopressins (vasopressin receptor agonists and antagonists) found in C. geographus and C. tulipa venom failed to produce a nirvana cabal-like effect in zebrafish.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31780714", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 986, "text": "In contrast, low concentrations of the non-competitive adrenoceptor antagonist \u03c1-TIA found in C. tulipa venom (EC50\u2009=\u2009190\u2009nM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31780714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "A peptide contained in the venom of the predatory marine snail Conus tulipa, rho-TIA, has previously been shown to possess alpha1-adrenoreceptor antagonist activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12824165", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 401, "text": "In this study, we examined the antinociceptive and motor effects of cone snail venom-derived peptides, conantokins G and T (conG and conT), which are selective inhibitors of the NR2B or NR2A and NR2B subtypes of the NMDA receptor, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12507705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12507705", "endSection": "title" } ] }, { "body": "Which component of the Influenza A Virus affects mRNA transcription termination?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21118126", "http://www.ncbi.nlm.nih.gov/pubmed/6328745", "http://www.ncbi.nlm.nih.gov/pubmed/29768209", "http://www.ncbi.nlm.nih.gov/pubmed/30177761", "http://www.ncbi.nlm.nih.gov/pubmed/18631147", "http://www.ncbi.nlm.nih.gov/pubmed/21207185", "http://www.ncbi.nlm.nih.gov/pubmed/1371285" ], "ideal_answer": [ "Defective Pol II termination occurs independently of the ability of the viral NS1 protein to interfere with host mRNA processing. Instead, this termination defect is a common effect of diverse cellular stresses and underlies the production of previously reported downstream-of-gene transcripts (DoGs).", "Influenza A virus (IAV) infection induces global transcriptional defects at the 3' ends of active host genes and RNA polymerase II (RNAPII) run-through into extragenic regions. This phenomenon occurs with multiple strains of IAV, is dependent on influenza NS1 protein, and can be modulated by SUMOylation of an intrinsically disordered region (IDR) of NS1 expressed by the 1918 pandemic IAV strain" ], "exact_answer": [ "NS1", "The IAV NS1 protein" ], "type": "factoid", "id": "5e4e3cee6d0a277941000030", "snippets": [ { "offsetInBeginSection": 2059, "offsetInEndSection": 2232, "text": "Optimized conditions are presented for the T7 and SP6 phage polymerase systems to minimize these early termination events during in vitro transcription of H5 influenza vRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21207185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Viruses have evolved a number of translational control mechanisms to regulate the levels of expression of viral proteins on polycistronic mRNAs, including programmed ribosomal frameshifting and stop codon readthrough.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18631147", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 350, "text": "More recently, another unusual mechanism has been described, that of termination-dependent re-initiation (also known as stop-start).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18631147", "endSection": "abstract" }, { "offsetInBeginSection": 1122, "offsetInEndSection": 1464, "text": "We conclude that (-)-carbovir 5'-triphosphate is a potent inhibitor of the HIV-1 reverse transcriptase enzyme and that (-)-carbovir most likely inhibits HIV by activity at the triphosphate level by a combination of direct competition for binding of the natural deoxynucleoside triphosphates to the reverse transcriptase and chain termination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1371285", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 291, "text": " One such mechanism, that of termination-dependent reinitiation, has been described in a number of both negative- and positive-strand RNA viruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118126", "endSection": "abstract" }, { "offsetInBeginSection": 459, "offsetInEndSection": 708, "text": " For example, the segment 7 RNA of influenza B is dicistronic, and the stop codon of the M1 ORF and the start codon of the BM2 ORF overlap in the pentanucleotide UAAUG (the stop codon of M1 is shown in bold and the start codon of BM2 is underlined).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118126", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1220, "text": "The present review summarizes how such interactions regulate reinitiation in an array of RNA viruses, and discusses what is known about reinitiation in viruses that do not rely on apparent mRNA-rRNA interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21118126", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 396, "text": "Using cell biological, biochemical, and genetic tools, we reveal that influenza A virus (IAV) infection induces global transcriptional defects at the 3' ends of active host genes and RNA polymerase II (RNAPII) run-through into extragenic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30177761", "endSection": "abstract" }, { "offsetInBeginSection": 637, "offsetInEndSection": 857, "text": "This phenomenon occurs with multiple strains of IAV, is dependent on influenza NS1 protein, and can be modulated by SUMOylation of an intrinsically disordered region (IDR) of NS1 expressed by the 1918 pandemic IAV strain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30177761", "endSection": "abstract" }, { "offsetInBeginSection": 914, "offsetInEndSection": 1111, "text": "These studies establish that during influenza virus infections processing of the NS1 mRNA transcript undergoes a mechanism of splicing similar to that occurring with DNA-directed RNA transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6328745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Influenza virus gene 8 codes for two nonstructural proteins (NS1 and NS2) which are translated, respectively, from a colinear and an interrupted mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6328745", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 714, "text": "Defective Pol II termination occurs independently of the ability of the viral NS1 protein to interfere with host mRNA processing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29768209", "endSection": "abstract" } ] }, { "body": "Which two genes are predominantly considered by warfarin initial dosing algorithms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32710457", "http://www.ncbi.nlm.nih.gov/pubmed/31673144" ], "ideal_answer": [ "Polymorphisms in CYP2C9 and VKORC1 are taken into consideration by warfarin initial dosing algorithms." ], "exact_answer": [ [ "CYP2C9" ], [ "VKORC1" ] ], "type": "list", "id": "606a23c694d57fd87900004d", "snippets": [ { "offsetInBeginSection": 392, "offsetInEndSection": 570, "text": " 507 adults were randomized to receive initial dosing as determined by an algorithm containing genetic (VKORC1 and CYP2C9) plus clinical information or only clinical information.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32710457", "endSection": "abstract" } ] }, { "body": "Describe MSstatsTMT", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32680918" ], "ideal_answer": [ "MSstatsTMT is a general statistical approach for relative protein quantification in MS- based experiments with TMT labeling." ], "type": "summary", "id": "606080eb94d57fd879000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "MSstatsTMT: Statistical Detection of Differentially Abundant Proteins in Experiments with Isobaric Labeling and Multiple Mixtures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32680918", "endSection": "title" }, { "offsetInBeginSection": 756, "offsetInEndSection": 1678, "text": "This manuscript proposes a general statistical approach for relative protein quantification in MS- based experiments with TMT labeling. It is applicable to experiments with multiple conditions, multiple biological replicate runs and multiple technical replicate runs, and unbalanced designs. It is based on a flexible family of linear mixed-effects models that handle complex patterns of technical artifacts and missing values. The approach is implemented in MSstatsTMT, a freely available open-source R/Bioconductor package compatible with data processing tools such as Proteome Discoverer, MaxQuant, OpenMS, and SpectroMine. Evaluation on a controlled mixture, simulated datasets, and three biological investigations with diverse designs demonstrated that MSstatsTMT balanced the sensitivity and the specificity of detecting differentially abundant proteins, in large-scale experiments with multiple biological mixtures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32680918", "endSection": "abstract" } ] }, { "body": "Is Tranexamic acid effective for intracerebral haemorrhage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31322116", "http://www.ncbi.nlm.nih.gov/pubmed/32637645", "http://www.ncbi.nlm.nih.gov/pubmed/29778325", "http://www.ncbi.nlm.nih.gov/pubmed/31008298", "http://www.ncbi.nlm.nih.gov/pubmed/33128912" ], "ideal_answer": [ "No. According to clinical trial data tranexamic acid does not improve outcomes of patients with intracerebral haemorrhage." ], "exact_answer": "no", "type": "yesno", "id": "6025ddde1cb411341a0000ba", "snippets": [ { "offsetInBeginSection": 1581, "offsetInEndSection": 1687, "text": "Tranexamic acid did not increase the risk of post-intracerebral haemorrhage seizures in the first 90\u2009days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32637645", "endSection": "abstract" }, { "offsetInBeginSection": 2014, "offsetInEndSection": 2777, "text": "The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0\u00b772 [95% CI 0\u00b732-1\u00b759], p=0\u00b741). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.INTERPRETATION: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33128912", "endSection": "abstract" }, { "offsetInBeginSection": 2840, "offsetInEndSection": 3097, "text": "CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31322116", "endSection": "abstract" }, { "offsetInBeginSection": 2155, "offsetInEndSection": 2400, "text": "INTERPRETATION: Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29778325", "endSection": "abstract" }, { "offsetInBeginSection": 804, "offsetInEndSection": 1078, "text": "Of these, two randomised controlled trials (RCTs) comparing intravenous tranexamic acid to placebo (n\u2009=\u200954) reported no significant difference in death or dependency. Three observational studies (n\u2009=\u2009281) suggested less haematoma growth with rapid tranexamic acid infusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31008298", "endSection": "abstract" } ] }, { "body": "Are interferons defensive proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31711273", "http://www.ncbi.nlm.nih.gov/pubmed/31783148", "http://www.ncbi.nlm.nih.gov/pubmed/32827605", "http://www.ncbi.nlm.nih.gov/pubmed/32755617" ], "ideal_answer": [ "Yes,\nThe innate immune system, in particular the type I interferon (IFN) response, is a powerful defence against virus infections." ], "exact_answer": "yes", "type": "yesno", "id": "60490dc71cb411341a000167", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "In response to viral infections, various pattern recognition receptors (PRRs) are activated for the production of type I interferon (IFN I). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32827605", "endSection": "abstract" }, { "offsetInBeginSection": 50, "offsetInEndSection": 147, "text": " activating interferon (IFN) production and positively regulating antiviral response in mammals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "The innate immune system, in particular the type I interferon (IFN) response, is a powerful defence against virus infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31711273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "The interferon-induced GTP-binding protein Mx is responsible for a specific antiviral state against a broad spectrum of viral infections that are induced by type-I interferons (IFN \u03b1/\u03b2) in different vertebrates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31783148", "endSection": "abstract" } ] }, { "body": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32619204", "http://www.ncbi.nlm.nih.gov/pubmed/28300758", "http://www.ncbi.nlm.nih.gov/pubmed/32234879", "http://www.ncbi.nlm.nih.gov/pubmed/32466845", "http://www.ncbi.nlm.nih.gov/pubmed/23595869", "http://www.ncbi.nlm.nih.gov/pubmed/23013531", "http://www.ncbi.nlm.nih.gov/pubmed/28736511", "http://www.ncbi.nlm.nih.gov/pubmed/29214616", "http://www.ncbi.nlm.nih.gov/pubmed/27844051", "http://www.ncbi.nlm.nih.gov/pubmed/23011466", "http://www.ncbi.nlm.nih.gov/pubmed/21463646", "http://www.ncbi.nlm.nih.gov/pubmed/12387309", "http://www.ncbi.nlm.nih.gov/pubmed/25461402", "http://www.ncbi.nlm.nih.gov/pubmed/32429534", "http://www.ncbi.nlm.nih.gov/pubmed/30038844", "http://www.ncbi.nlm.nih.gov/pubmed/28666801", "http://www.ncbi.nlm.nih.gov/pubmed/27447722", "http://www.ncbi.nlm.nih.gov/pubmed/26684635", "http://www.ncbi.nlm.nih.gov/pubmed/17516722", "http://www.ncbi.nlm.nih.gov/pubmed/33114764", "http://www.ncbi.nlm.nih.gov/pubmed/32562081", "http://www.ncbi.nlm.nih.gov/pubmed/19336900" ], "ideal_answer": [ "Methylsulfonylmethane (MSM) is a sulfur-based nutritional supplement that is purported to have pain and inflammation-reducing effects.", "Methylsulfonylmethane (MSM) is an anti-inflammatory drug with anti-proinflammatory activity", "Methylsulfonylmethane (MSM) exerts anti-inflammatory effects in animal models of inflammation", "These findings indicate that MSM may protect against inflammation in the heart", "Methylsulfonylmethane (MSM) is an anti-inflammatory agent that acts by inhibiting inflammatory cytokine production and epithelial cell proliferation and differentiation.", "Methylsulfonylmethane (MSM) exerts anti-inflammatory activity in the body", "Methylsulfonylmethane (MSM) is a naturally occurring compound that demonstrates anti-inflammatory effects in humans and various animal and cell culture models.", "Methylsulfonylmethane (MSM) is a sulfur-based compound that is purported to have anti-inflammatory and inflammation-reducing effects. URL_0" ], "exact_answer": [ "reduces inflammation" ], "type": "factoid", "id": "5e52cb6d6d0a277941000050", "snippets": [ { "offsetInBeginSection": 415, "offsetInEndSection": 575, "text": "Methylsulfonylmethane (MSM) is a naturally occurring compound that demonstrates anti-inflammatory effects in humans and various animal and cell culture models. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Methylsulfonylmethane decreases inflammatory response to tumor necrosis factor-\u03b1 in cardiac cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038844", "endSection": "title" }, { "offsetInBeginSection": 1657, "offsetInEndSection": 1735, "text": "These findings indicate that MSM may protect against inflammation in the heart", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28300758", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 374, "text": "Methylsulfonylmethane (MSM) is a sulfur-based nutritional supplement that is purported to have pain and inflammation-reducing effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736511", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 172, "text": "d with strenuous exercise and methylsulfonylmethane (MSM) has been shown to have anti-inflammatory properties. Methods. Physically acti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27844051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "BACKGROUND: Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32562081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Methylsulfonylmethane (MSM), which is one of the popular ingredients of so-called health foods in Japan, is expected to relieve inflammation in arthritis and allergies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23011466", "endSection": "abstract" }, { "offsetInBeginSection": 415, "offsetInEndSection": 574, "text": "Methylsulfonylmethane (MSM) is a naturally occurring compound that demonstrates anti-inflammatory effects in humans and various animal and cell culture models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: Methylsulfonylmethane (MSM) is a naturally occurring sulfur containing substance that has been shown to have anti-inflammatory and antioxidative ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29214616", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 587, "text": "ylmethane (MSM) is a naturally occurring compound that demonstrates anti-inflammatory effects in humans and various animal and cell culture models. The effects ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23595869", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 138, "text": "ckground. Inflammation is associated with strenuous exercise and methylsulfonylmethane (MSM) has been shown to have anti-inflammatory pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27844051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "BACKGROUND/AIM: Methylsulfonylmethane (MSM) is a natural organic compound that displays anti-inflammatory as well as antioxid", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32234879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Methylsulfonylmethane (MSM), naturally occurring in green plants, fruits and vegetables, has been shown to exert anti-inflammatory and antioxidant effects. MS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21463646", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 364, "text": "sistence. Methylsulfonylmethane (MSM) is a sulfur-based nutritional supplement that is purported to have pain and inflammation-reducing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736511", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 497, "text": " sulfur (NTS) and methylsulfonylmethane (MSM) are two sulfur-containing natural compounds that can induce anti-inflammation. Using Weste", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32429534", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 646, "text": "ylsulfonylmethane (MSM) (Barentz, Paderno Dugnano, Italy) has proven to have anti-inflammatory properties and to cause pain relief in patients affected by tendinopathies. This study aims at ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33114764", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 359, "text": "mance. A recent study found that dietary polyphenols and methlysulfonylmethane (MSM) can reduce systemic inflammation and oxidative stress without adverse side ef", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32619204", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Methylsulfonylmethane (MSM), which is one of the popular ingredients of so-called health foods in Japan, is expected to relieve inflammation in arthritis and allergies. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23011466", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND: Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32562081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28300758", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 347, "text": "ylsulfonylmethane (MSM) and boswellic acids (BA) are new effective supplements for the management of inflammation and joint degeneration, according to previous experimental studies. The aim", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26684635", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 372, "text": " Methylsulfonylmethane (MSM) is a sulfur-based nutritional supplement that is purported to have pain and inflammation-reducing effects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736511", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 147, "text": "Inflammation is associated with strenuous exercise and methylsulfonylmethane (MSM) has been shown to have anti-inflammatory properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27844051", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Methylsulfonylmethane (MSM) is a popular dietary supplement used in a variety of conditions including pain, inflammation, allergies, arthritis, parasitic infections and the maintenance of normal keratin levels in hair, skin and nails.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12387309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "BACKGROUND: Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32562081", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 485, "text": "Non-toxic sulfur (NTS) and methylsulfonylmethane (MSM) are two sulfur-containing natural compounds that can induce anti-inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32429534", "endSection": "abstract" }, { "offsetInBeginSection": 371, "offsetInEndSection": 572, "text": "Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-documented anti-oxidant and anti-inflammatory properties; currently its effects on osteoclast differentiation are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27447722", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 559, "text": "Methylsulfonylmethane (MSM) is a sulfur compound with well-known anti-inflammatory effects but its effects on bone regeneration are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32466845", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 626, "text": "Recently, methylsulfonylmethane (MSM) (Barentz, Paderno Dugnano, Italy) has proven to have anti-inflammatory properties and to cause pain relief in patients affected by tendinopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33114764", "endSection": "abstract" }, { "offsetInBeginSection": 504, "offsetInEndSection": 688, "text": "In our results, MSM significantly attenuated NLRP3 inflammasome activation in lipopolysaccharide-primed macrophages, although it had no effect on NLCR4 or AIM2 inflammasome activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25461402", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 802, "text": "Extracts of MSM-enriched vegetables presented the same inhibitory effect on NLRP3 inflammasome activation as MSM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25461402", "endSection": "abstract" }, { "offsetInBeginSection": 1657, "offsetInEndSection": 1790, "text": "These findings indicate that MSM may protect against inflammation in the heart, and thereby protect against inflammation-linked CVDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30038844", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 287, "text": "MSM has protective effects against various disorders through its anti-inflammatory and antioxidant properties however the effect of MSM on gastric mucosal injury remains unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28666801", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1204, "text": "MSM suppressed gastric inflammation by reducing the levels of proinflammatory cytokines tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-1\u03b2, IL-6, monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28666801", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Methylsulfonylmethane (MSM), naturally occurring in green plants, fruits and vegetables, has been shown to exert anti-inflammatory and antioxidant effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21463646", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19336900", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 257, "text": "ive agent. Methylsulfonylmethane (MSM), the isoxidised form of dimethyl-sulfoxide (DSMO), is an effective natural analgesic and anti-inflamma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17516722", "endSection": "abstract" }, { "offsetInBeginSection": 888, "offsetInEndSection": 1050, "text": "Taken together, these results show that MSM has anti-inflammatory characteristics, interrupts NLRP3 inflammasome activation, and inhibits pro-cytokine expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25461402", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BACKGROUND: Methylsulfonylmethane (MSM) has been reported to provide anti-inflammatory and antioxidant effects in both ani", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23013531", "endSection": "abstract" } ] }, { "body": "What is particular about the 3D structure of the inactive X chromosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29654302", "http://www.ncbi.nlm.nih.gov/pubmed/26248554", "http://www.ncbi.nlm.nih.gov/pubmed/27062886", "http://www.ncbi.nlm.nih.gov/pubmed/18789978", "http://www.ncbi.nlm.nih.gov/pubmed/27492478" ], "ideal_answer": [ "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. This specific bipartite organization of the inactive X chromosome that probably plays an important role in maintenance of gene silencing.", "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Despite the importance of X chromosome inactivation, little is known about this 3D conformation. The inactive X chromosomes are the best examples of XCI in females, originally discovered as a compact 3D structure at the nuclear periphery known as the Barr body.", "The inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region that is enriched in histone H3 lysine 27.", "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region.", "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomain differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus. Genes that escape X inactivation do not cluster but are located near a periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase." ], "type": "summary", "id": "5fdb2f03a43ad31278000010", "snippets": [ { "offsetInBeginSection": 403, "offsetInEndSection": 596, "text": "How Xist RNA attaches to and propagates across a chromosome and its influence over the three-dimensional (3D) structure of the inactive X are aspects of XCI that have remained largely unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27062886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "The Xist long noncoding RNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27492478", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 811, "text": "Our results demonstrate that lamina recruitment changes the 3D structure of DNA, enabling Xist and its silencing proteins to spread across the X to silence transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27492478", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 775, "text": "The inactive X has two superdomains of frequent intrachromosomal contacts separated by a boundary region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomains differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26248554", "endSection": "abstract" }, { "offsetInBeginSection": 908, "offsetInEndSection": 1062, "text": "Genes that escape X inactivation do not cluster but are located near the periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26248554", "endSection": "abstract" }, { "offsetInBeginSection": 1469, "offsetInEndSection": 1609, "text": "a specific bipartite organization of the mouse inactive X chromosome that probably plays an important role in maintenance of gene silencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26248554", "endSection": "abstract" }, { "offsetInBeginSection": 610, "offsetInEndSection": 888, "text": "e have applied these approaches to analyze 3D microscopy images of the X-chromosome where four consecutive genomic regions (BACs) have been simultaneously labeled by multicolor FISH. We have acquired two sets of four consecutive genomic regions with an overlap of three regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18789978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29654302", "endSection": "abstract" } ] }, { "body": "Why mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28696420" ], "ideal_answer": [ "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine." ], "type": "summary", "id": "606ad4bd94d57fd879000054", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28696420", "endSection": "abstract" } ] }, { "body": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32717044" ], "ideal_answer": [ "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation. It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages.", "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called Thermal proximity coaggregation. It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages.", "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA). Rtpca can be used for high-throughput intracellular monitoring of protein complex dynamics.", "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA). Rtpca was reported to be able to integrate downloaded protein/protein interaction information from different online databases with private data to construct new and personalized interaction networks.", "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA).", "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA). It offers user-friendly tools to explore datasets for their protein-protein interaction predictive performance and easily integrates with available R packages.", "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA)", "Rtpca is an R package for differential thermal proximity coaggregation analysis. It is based on a model of thermal proximity (TFD) analysis performed by combining multiple layers of TSSs with TSSS (TSC) and TSSF (TSS-FANCA) data.", "Rtpca is an R package implementing methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation.", "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called Thermal proximity coaggregation (TPCA). It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages.", "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on Thermal proteome profiling experiments or in a differential setting via an approach called Thermal proximity coaggregation. It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages.", "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA) It offers user-friendly tools to explore datasets for their protein-protein interaction predictive performance and easily integrates with available R packages." ], "exact_answer": [ "Rtpca" ], "type": "factoid", "id": "606074ab94d57fd87900003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Rtpca: an R package for differential thermal proximity coaggregation analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32717044", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 594, "text": "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA). It offers user-friendly tools to explore datasets for their protein-protein interaction predictive performance and easily integrates with available R packages.AVAILABILITY: Rtpca is available from Bioconductor (https://bioconductor.org/packages/Rtpca).SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32717044", "endSection": "abstract" } ] }, { "body": "What is the mechanisms of action of Evinacumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "http://www.ncbi.nlm.nih.gov/pubmed/33295805", "http://www.ncbi.nlm.nih.gov/pubmed/32332430", "http://www.ncbi.nlm.nih.gov/pubmed/32813947", "http://www.ncbi.nlm.nih.gov/pubmed/31843957", "http://www.ncbi.nlm.nih.gov/pubmed/32492513", "http://www.ncbi.nlm.nih.gov/pubmed/31578082", "http://www.ncbi.nlm.nih.gov/pubmed/31008773", "http://www.ncbi.nlm.nih.gov/pubmed/32520777", "http://www.ncbi.nlm.nih.gov/pubmed/30403015", "http://www.ncbi.nlm.nih.gov/pubmed/32841138", "http://www.ncbi.nlm.nih.gov/pubmed/33278127", "http://www.ncbi.nlm.nih.gov/pubmed/28538136", "http://www.ncbi.nlm.nih.gov/pubmed/33196153", "http://www.ncbi.nlm.nih.gov/pubmed/30011918", "http://www.ncbi.nlm.nih.gov/pubmed/32511037", "http://www.ncbi.nlm.nih.gov/pubmed/31100030", "http://www.ncbi.nlm.nih.gov/pubmed/31242752" ], "ideal_answer": [ "Evinacumab is angiopoietin-like protein 3 (ANGPTL3) monoclonal antibody that was shown to substantially reduce low-density lipoprotein cholesterol concentration." ], "type": "summary", "id": "601c33f81cb411341a000017", "snippets": [ { "offsetInBeginSection": 1061, "offsetInEndSection": 1220, "text": "Evinacumab, a monoclonal antibody against ANGPTL3, has been shown to substantially reduce LDL-C of an average of 49%, independently of residual LDLR activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32332430", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1255, "text": "RECENT FINDINGS: Novel therapies, not dependent on a functioning LDLR include lomitapide and mipomersen, which decrease hepatic apolipoprotein B secretion, and evinacumab, directed at the angiopoietin like-3 protein (ANGPLT-3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32520777", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1169, "text": "Multiple ANGPLT3 inhibitors (evinacumab, IONIS-ANGPTL3-LRx, ARO-ANG3) effectuate TG reductions up to 70% with concomitant potent reduction in all other apoB containing lipoprotein fractions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32511037", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1118, "text": "Moreover, regarding TG a monoclonal antibody called evinacumab and an antisense-oligonucleotide against ANGPTL3 showed effective TG-lowering. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492513", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 474, "text": "Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab, monoclonal antibodies against cholesterol-regulating proprotein convertase subtilisin/kexin type 9 and angiopoietin-like protein 3, may provide more benefit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31843957", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 638, "text": "Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32813947", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1711, "text": "These include an antisense oligonucleotide against apoC-III (volanesorsen), a monoclonal antibody against angiopoietin-like protein-3 (evinacumab), and other agents currently in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32841138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND AND AIMS: Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, reduced low-density lipoprotein cholesterol (LDL-C) significantly in a Phase 2 study of patients with homozygous familial hypercholesterolemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 943, "text": "e I clinical trials with a monoclonal anti-ANGPTL3 antibody (evinacumab) and anti-sense oligonucleotide (ASO) clearly show a significant lipid lowering effect. In addition, from t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30011918", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 630, "text": "ease. A phase 2, proof-of-concept study (NCT02265952) demonstrated that evinacumab, a fully human monoclonal antibody to ANGPTL3 (angiopoietin-like 3 protein), reduced LDL-C levels in 9 patients with genotypically confirmed homozygous familial hypercholesterolemia and was well tolerated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31578082", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1134, "text": "ng TG a monoclonal antibody called evinacumab and an antisense-oligonucleotide against ANGPTL3 showed effective TG-lowering. At least, using ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492513", "endSection": "abstract" }, { "offsetInBeginSection": 969, "offsetInEndSection": 1162, "text": "Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30403015", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 1068, "text": "fter an attentive literature search, the authors resumed here information on proprotein convertase subtilisin/kexin 9 inhibitors (evolocumab and alirocumab), small interfering RNA molecule inclisiran, antisense oligonucleotides (mipomersen, volanesorsen, ISIS 681257), and drugs targeting angiopoietin-like protein 3 (evinacumab, IONIS-ANGPTL3Rx).E", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31100030", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 397, "text": " Evinacumab, an ANGPTL3 inhibitor, reduced triglycerides in healthy human volunteers and in homozygous familial hypercholesterolemic individuals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31242752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "A randomized study investigating the safety, tolerability, and pharmacokinetics of evinacumab, an ANGPTL3 inhibitor, in healthy Japanese and Caucasian subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "BACKGROUND AND AIMS: Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, reduced low-density lipoprotein cholesterol (LDL-C) significantly in a Phase 2 study of patients with homozygous familial hypercholesterolemia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 386, "text": "her lipids. Evinacumab, an ANGPTL3 inhibitor, reduced triglycerides in healthy human volunteers and in homozygous familial hypercholesterolemic ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31242752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND AND AIMS: Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, reduced low-density lipoprotein cholesterol (LDL-C) significantly in a Phase 2 study of patients with homozygous familial ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 949, "text": "ar disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia.METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) ever", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32813947", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 620, "text": "r disease. A phase 2, proof-of-concept study (NCT02265952) demonstrated that evinacumab, a fully human monoclonal antibody to ANGPTL3 (angiopoietin-like 3 protein), reduced LDL-C levels in 9 patients with genotypically confirmed homozygous familial hypercholesterolemia and was well", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31578082", "endSection": "abstract" }, { "offsetInBeginSection": 1028, "offsetInEndSection": 1451, "text": "equire LDL receptor (LDLR) activity. Evinacumab, a novel monoclonal antibody against angiopoetin-like 3 (ANGPTL3), reduces LDL-C by 50% independent of LDLR activity.SUMMARY: Achieving a target LDL-C in familial hypercholesterolemia can be challenging with standard LLT; however, novel therapeutic modalities show remarkable reductions in LDL-C allowing nearly all patients with HeFH and a significant proportion of patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33278127", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 403, "text": " In such patients, the efficacy and safety of subcutaneous and intravenous evinacumab, a fully human monoclonal antibody against angiopoietin-like 3, are not known", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33196153", "endSection": "abstract" }, { "offsetInBeginSection": 797, "offsetInEndSection": 1010, "text": "We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28538136", "endSection": "abstract" } ] }, { "body": "Do honey contain diastases/amylases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/595894", "http://www.ncbi.nlm.nih.gov/pubmed/17995872", "http://www.ncbi.nlm.nih.gov/pubmed/32424606", "http://www.ncbi.nlm.nih.gov/pubmed/22483889" ], "ideal_answer": [ "Yes\nhoney contain the protein amylase." ], "exact_answer": "yes", "type": "yesno", "id": "60354a7b1cb411341a000154", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "A new rapid method for the determination of honey diastase activity using direct potentiometric principles has been proposed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22483889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "The major alpha-amylase in honey was characterized. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17995872", "endSection": "abstract" }, { "offsetInBeginSection": 29, "offsetInEndSection": 56, "text": "Separation of honey amylase", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/595894", "endSection": "title" } ] }, { "body": "What year was the first successful human heart transplant performed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11391041", "http://www.ncbi.nlm.nih.gov/pubmed/18702960", "http://www.ncbi.nlm.nih.gov/pubmed/15056065", "http://www.ncbi.nlm.nih.gov/pubmed/15726762", "http://www.ncbi.nlm.nih.gov/pubmed/32493185", "http://www.ncbi.nlm.nih.gov/pubmed/15061629", "http://www.ncbi.nlm.nih.gov/pubmed/19287813", "http://www.ncbi.nlm.nih.gov/pubmed/30083541", "http://www.ncbi.nlm.nih.gov/pubmed/29191294", "http://www.ncbi.nlm.nih.gov/pubmed/31102725", "http://www.ncbi.nlm.nih.gov/pubmed/6378042", "http://www.ncbi.nlm.nih.gov/pubmed/25795463", "http://www.ncbi.nlm.nih.gov/pubmed/29664541", "http://www.ncbi.nlm.nih.gov/pubmed/29262951", "http://www.ncbi.nlm.nih.gov/pubmed/10272755", "http://www.ncbi.nlm.nih.gov/pubmed/16009314", "http://www.ncbi.nlm.nih.gov/pubmed/29492391", "http://www.ncbi.nlm.nih.gov/pubmed/32065475" ], "ideal_answer": [ "The first human heart transplant in 1967 was performed using a deceased donor heart,", "the first human heart transplant in 1967 was performed using a deceased donor heart," ], "exact_answer": [ "1967" ], "type": "factoid", "id": "601ee4c61cb411341a000066", "snippets": [ { "offsetInBeginSection": 474, "offsetInEndSection": 558, "text": "the first human heart transplant in 1967 was performed using a deceased donor heart,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31102725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "In 1967, Christian Barnard performed the first successful human-to-human heart transplant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15056065", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 411, "text": "Since the first successful human heart transplant performed by Christiaan Barnard in 1967, there has been substantial progress in the field of heart transplantation, especially over the last several decades.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16009314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "In 2017, we celebrated the 50th anniversary of the first human heart transplant that had been carried out by the South African surgeon, Christiaan ('Chris') Barnard at Groote Schuur Hospital in Cape Town on December 3rd, 1967. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30083541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "It has been 40 years since the first human-to-human heart transplant performed in South Africa by Christiaan Barnard in December 1967", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18702960", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 417, "text": " the first successful human heart transplant performed by Christiaan Barnard in 1967, there has been substantial progress in the field of heart transplantation, especially over the last several decades. With ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16009314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Since the first human heart transplantation was performed in 1967, the field of heart transplantation has advanced to the point where survival and acceptable quality of life are commonplace.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11391041", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The first human-to-human heart transplant was performed 50 years ago in 1967", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29492391", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 435, "text": "Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. Howeve", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32493185", "endSection": "abstract" }, { "offsetInBeginSection": 474, "offsetInEndSection": 729, "text": "the first human heart transplant in 1967 was performed using a deceased donor heart, the advent of brain death criteria and the ability to avoid long warm ischemic times led donation after cardiac death (DCD) transplantation to fall out of favor. Due the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31102725", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The Human Tissue Act of 1983 had its origin in the first successful heart transplant operation performed by Professor Christiaan Barnard and his team in December 1967", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15726762", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "It has been 50 years since Dr. Christiaan Barnard performed the first human-to-human heart transplant in December 1967\u00a0in\u00a0South Africa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29191294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The first successful human heart transplantation was reported on 3 December 1967, by Christiaan Barnard in South Africa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32065475", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The world's first human-to-human heart transplant was performed at Groote Schuur Hospital on the 2nd December 1967.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6378042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "50 years have passed since the first human to human heart transplantation, performed by Christiaan Barnard in Cape Town December 3rd 1967.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29664541", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 386, "text": "In 1967, he led the team that performed the world's first human-to-human heart transplant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19287813", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 383, "text": " a century. From the repair of the first septal defect in 1953, followed by the first successful heart transplant in 1967, and later to the first infusion of bone marrow-derived cells to the human myocardium in 2002, significant progress has been made in h", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25795463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Article on the first heart transplant, performed at Groote Schuur Hospital, Cape Town, on 3 December 1967.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29262951", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 297, "text": "On December 3, 1967, in Cape Town, South Africa, Dr. Christian Barnard revolutionized organ transplantation with the first successful human heart transplant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10272755", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 414, "text": "Barnard performed the 1st human-to-human orthotopic heart transplantation in 1967 and followed this by introducing the technique of heterotopic heart transplantation in 1974.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15061629", "endSection": "abstract" } ] }, { "body": "Which disease is monitored in the BIOCURA cohort?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28650254", "http://www.ncbi.nlm.nih.gov/pubmed/27631111", "http://www.ncbi.nlm.nih.gov/pubmed/29808722", "http://www.ncbi.nlm.nih.gov/pubmed/27558398", "http://www.ncbi.nlm.nih.gov/pubmed/27749223" ], "ideal_answer": [ "Rheumatoid Arthritis (RA) is one of the diseases that is monitored in the BIOCURA cohort. There are other diseases that are monitored as well, such as breast cancer, ovarian cancer, and thyroid cancer.", "BiOCura cohort is used to monitor rheumatoid arthritis.", "The BiOCURA registry includes patient with Rheumatoid Arthritis (RA) with the aim of defining their response profile to different RA treatments.", "BiOCura cohort is used for clinical monitoring of rheumatoid arthritis." ], "exact_answer": [ "Rheumatoid Arthritis", "RA" ], "type": "factoid", "id": "5fe3130ca43ad3127800003e", "snippets": [ { "offsetInBeginSection": 326, "offsetInEndSection": 471, "text": "In RA patients eligible for biological treatment included in the BiOCURA registry, 53 inflammatory proteins were measured using xMAP\u00ae technology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28650254", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 411, "text": "Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice.METHODS: The eighty most extreme responders and nonresponders to TNFi therapy were selected from the observational BiOCURA cohort. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29808722", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 528, "text": "In the metabolomic profiling, lipids, oxylipins, and amines were measured in serum samples of RA patients from the observational BiOCURA cohort, before start of biological treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27631111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "In clinical practice, approximately one-third of patients with rheumatoid arthritis (RA) respond insufficiently to TNF-\u03b1 inhibitors (TNFis). The aim of the study was to explore the use of a metabolomics to identify predictors for the outcome of TNFi therapy, and study the metabolomic fingerprint in active RA irrespective of patients' response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27631111", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 474, "text": "From the observational BiOCURA cohort, 40 adalimumab- (ADA) and 40 etanercept- (ETN) treated patients were selected to enter the discovery cohort and baseline serum profiling on 758 miRNAs was performed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27558398", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 425, "text": "Despite the success of TNF-alpha inhibitor (TNFi) treatment in rheumatoid arthritis (RA), a substantial number of patients necessitate discontinuation. Prediction thereof would be clinically relevant and guide the decision whether to start TNFi treatment.METHODS: Data were used from the observational BiOCURA cohort, in which patients initiating biological treatment were enrolled and followed up for one year. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27749223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "BACKGROUND: Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29808722", "endSection": "abstract" } ] }, { "body": "Which gene is associated with response to abacavir?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23204921" ], "ideal_answer": [ "Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir." ], "exact_answer": [ "HLA-B" ], "type": "factoid", "id": "606aea9b94d57fd879000058", "snippets": [ { "offsetInBeginSection": 398, "offsetInEndSection": 507, "text": "Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23204921", "endSection": "abstract" } ] }, { "body": "Is adenosine signaling prognostic for cancer outcome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31953314" ], "ideal_answer": [ "Yes, adenosine signaling has been shown to be prognostic for cancer outcome.", "Yes, adenosine signaling is prognostic for cancer outcome.", "Yes. Adenosine signaling is prognostic for cancer outcome and has predictive utility for immunotherapeutic response." ], "exact_answer": "yes", "type": "yesno", "id": "601ecab41cb411341a000065", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Adenosine Signaling Is Prognostic for Cancer Outcome and Has Predictive Utility for Immunotherapeutic Response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31953314", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1845, "text": "There are several agents in early clinical trials targeting components of the adenosine pathway including A2AR and CD73. The identification of cancers with a significant adenosine drive is critical to understand the potential for these molecules. However, it is challenging to measure tumor adenosine levels at scale, thus novel, clinically tractable biomarkers are needed.EXPERIMENTAL DESIGN: We generated a gene expression signature for the adenosine signaling using regulatory networks derived from the literature and validated this in patients. We applied the signature to large cohorts of disease from The Cancer Genome Atlas (TCGA) and cohorts of immune checkpoint inhibitor-treated patients.RESULTS: The signature captures baseline adenosine levels in vivo (r 2 = 0.92, P = 0.018), is reduced after small-molecule inhibition of A2AR in mice (r 2 = -0.62, P = 0.001) and humans (reduction in 5 of 7 patients, 70%), and is abrogated after A2AR knockout. Analysis of TCGA confirms a negative association between adenosine and overall survival (OS, HR = 0.6, P < 2.2e-16) as well as progression-free survival (PFS, HR = 0.77, P = 0.0000006). Further, adenosine signaling is associated with reduced OS (HR = 0.47, P < 2.2e-16) and PFS (HR = 0.65, P = 0.0000002) in CD8+ T-cell-infiltrated tumors. Mutation of TGF\u03b2 superfamily members is associated with enhanced adenosine signaling and worse OS (HR = 0.43, P < 2.2e-16). Finally, adenosine signaling is associated with reduced efficacy of anti-PD1 therapy in published cohorts (HR = 0.29, P = 0.00012).CONCLUSIONS: These data support the adenosine pathway as a mediator of a successful antitumor immune response, demonstrate the prognostic potential of the signature for immunotherapy, and inform patient selection strategies for adenosine pathway modulators currently in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31953314", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the CNIC polypill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31850802", "http://www.ncbi.nlm.nih.gov/pubmed/31983653" ], "ideal_answer": [ "CNIC polypill includes atorvastatin 40mg, ramipril 10mg and aspirin 100mg." ], "exact_answer": [ [ "atorvastatin" ], [ "ramipril" ], [ "aspirin" ] ], "type": "list", "id": "60266b371cb411341a0000c2", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Aim: To determine the effectiveness of Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (acetylsalicylic acid 100\u00a0mg, ramipril 5/10\u00a0mg, simvastatin 40\u00a0mg) in achieving blood pressure (BP) goals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31850802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "INTRODUCTION AND OBJECTIVES: To compare the pharmacodynamics of the CNIC polypill (atorvastatin 40mg/ramipril 10mg/aspirin 100mg) in terms of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP), with the corresponding reference products (atorvastatin and ramipril).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31983653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Aim: To determine the effectiveness of Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (acetylsalicylic acid 100\u00a0mg, ramipril 5/10\u00a0mg, simvastatin 40\u00a0mg) in achieving blood pressure (BP) goals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31850802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "INTRODUCTION AND OBJECTIVES: To compare the pharmacodynamics of the CNIC polypill (atorvastatin 40mg/ramipril 10mg/aspirin 100mg) in terms of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP), with the corresponding reference products (atorvastatin and ramipril).METHODS: This was a multicenter, randomized, open-label, and parallel 3-arm study comparing the effect of the CNIC polypill vs ramipril 10mg a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31983653", "endSection": "abstract" } ] }, { "body": "Which human tissue synthesize CRP?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31758923", "http://www.ncbi.nlm.nih.gov/pubmed/31840602" ], "ideal_answer": [ "CRP is predominantly produced in the liver in a native pentameric form (nCRP)." ], "exact_answer": [ "liver" ], "type": "factoid", "id": "6032b6661cb411341a00014a", "snippets": [ { "offsetInBeginSection": 278, "offsetInEndSection": 420, "text": "The accumulating data suggests that CRP has two distinct forms. It is predominantly produced in the liver in a native pentameric form (nCRP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31840602", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 299, "text": "analysis of liver tissue from donors with pathologically elevated C-reactive protein (CRP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758923", "endSection": "abstract" } ] }, { "body": "What is the relationship between the X chromosome and a neutrophil drumstick?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28374668", "http://www.ncbi.nlm.nih.gov/pubmed/11534818", "http://www.ncbi.nlm.nih.gov/pubmed/3721910", "http://www.ncbi.nlm.nih.gov/pubmed/7828232", "http://www.ncbi.nlm.nih.gov/pubmed/7416166", "http://www.ncbi.nlm.nih.gov/pubmed/2176962" ], "ideal_answer": [ "In particular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome.", "In particular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome" ], "type": "summary", "id": "6025382b1cb411341a0000a5", "snippets": [ { "offsetInBeginSection": 325, "offsetInEndSection": 464, "text": "In particular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534818", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1361, "text": "The inactive X chromosome also exhibits a specific orientation within the drumstick appendage, with over 95% of nuclei having the X centromere located toward the tip of the appendage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "There is a marked difference between the frequencies of neutrophil nuclear drumsticks and mucosal cell Barr bodies in any given woman despite the fact that both represent an inactivated X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7828232", "endSection": "abstract" }, { "offsetInBeginSection": 1459, "offsetInEndSection": 1699, "text": "In addition, Barr bodies of characteristic drumstick appearance bearing inactive X chromosome in interphase nuclei of mature granulocytes in fertile female patients exhibited a heterochromatin condensation state similar to nuclear segments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28374668", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 657, "text": "Fluorescent staining can distinguish between true drumsticks bearing the inactive X of normal females and the pseudo-drumsticks in a normal male produced by a large Y chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7416166", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 470, "text": "articular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534818", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 356, "text": "This autoradiographic approach allowed the first direct demonstration of the presence of X chromosomal material in the drumstick-like structures of female polymorphonuclear leukocytes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3721910", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 918, "text": "y, in female neutrophil nuclei with a drumstick appendage, the active X chromosome is also randomly distributed among lobes. In contr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "There is a marked difference between the frequencies of neutrophil nuclear drumsticks and mucosal cell Barr bodies in any given woman despite the fact that both represent an inactivated X chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7828232", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 465, "text": "In particular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11534818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Demonstration of X chromatin in drumstick-like nuclear appendages of leukocytes by in situ hybridization on blood smears.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3721910", "endSection": "title" }, { "offsetInBeginSection": 547, "offsetInEndSection": 791, "text": "Moreover, we are the first to determine that sex-specific \"drumsticks\" and \"sessile nodules\" in female polymorphs originate from the X chromosomes and that non-sex-specific \"drumstick-like\" bodies in male polymorphs are of Y chromosomal origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2176962", "endSection": "abstract" } ] }, { "body": "The formation of which inflammatory molecule is regulated by MAP3K8 (TPL2)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20736176", "http://www.ncbi.nlm.nih.gov/pubmed/24517997", "http://www.ncbi.nlm.nih.gov/pubmed/30463908", "http://www.ncbi.nlm.nih.gov/pubmed/26215868", "http://www.ncbi.nlm.nih.gov/pubmed/19808894", "http://www.ncbi.nlm.nih.gov/pubmed/27261457", "http://www.ncbi.nlm.nih.gov/pubmed/32253104", "http://www.ncbi.nlm.nih.gov/pubmed/24586913", "http://www.ncbi.nlm.nih.gov/pubmed/19933865" ], "ideal_answer": [ "MAP3K8 (Tpl2) regulates the formation of inflammatory molecule IL-1\u03b2", "MAP3K8 (Tpl2) regulates the formation of IL-1\u03b2 by masking its inflammatory function.", "MAP3K8 (also known as Map3k8) regulates the formation of IL-1\u03b2", "IL-1\u03b2 formation is regulated by MAP3K8 (TPL2)", "Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1beta production and optimal host defense.", "MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1\u03b2 and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance." ], "exact_answer": [ "IL-1\u03b2", "IL1-beta" ], "type": "factoid", "id": "5fe31317a43ad31278000044", "snippets": [ { "offsetInBeginSection": 205, "offsetInEndSection": 306, "text": "Tpl2(-/-) macrophages have abrogated TNF production but overproduce IL-12 in response to TLR ligands.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933865", "endSection": "abstract" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1515, "text": "At this time, Cot/tpl2(-/-) mice showed significantly reduced NGF, TNF\u03b1, and prostaglandin E(2) levels compared with WT littermates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20736176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Hypoxia potentiates monocyte-derived dendritic cells for release of tumor necrosis factor alpha via MAP3K8.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30463908", "endSection": "title" }, { "offsetInBeginSection": 903, "offsetInEndSection": 1061, "text": "We identified MAP3K8 as a target gene of Hypoxia Induced Factor (HIF), a transcription factor controlled by oxygen tension, upstream of the p38/MAPK pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30463908", "endSection": "abstract" }, { "offsetInBeginSection": 1062, "offsetInEndSection": 1152, "text": "ypoxia increased expression of MAP3K8 concomitant with the potentiation of TNF-\u03b1 secretion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30463908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Interleukin-22 promotes epithelial cell transformation and breast tumorigenesis via MAP3K8 activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517997", "endSection": "title" }, { "offsetInBeginSection": 615, "offsetInEndSection": 748, "text": "IL-22 increased MAP3K8 phosphorylation through IL-22R1, followed by the induction of MEK-ERK, JNK-c-Jun, and STAT3 signaling pathways", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517997", "endSection": "abstract" }, { "offsetInBeginSection": 1560, "offsetInEndSection": 1728, "text": "Overall, our findings point to a critical role for the IL-22-induced MAP3K8 signaling pathway in promoting cancer-associated inflammation in the tumor microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24517997", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 496, "text": "We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1\u03b2, IL-6 and IL-8).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586913", "endSection": "abstract" }, { "offsetInBeginSection": 1499, "offsetInEndSection": 1741, "text": "Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1\u03b2 and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586913", "endSection": "abstract" }, { "offsetInBeginSection": 1358, "offsetInEndSection": 1457, "text": "we found that Tpl2 is essential for IL-1beta production from both macrophages and dendritic cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933865", "endSection": "abstract" }, { "offsetInBeginSection": 1481, "offsetInEndSection": 1667, "text": "Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1beta production and optimal host defense.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933865", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1218, "text": "how that the MAP3K8 called Tpl2 was expressed in adipocytes and that IL-1beta and TNF-alpha activated Tpl2 and regulated its expression through an IKKbeta pathway. Pha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The serine/threonine kinase tumor progression locus 2 (Tpl2, also known as Map3k8/Cot) is a potent inflammatory mediator that drives the production of TNF\u03b1, IL-1\u03b2, and IFN\u03b3. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27261457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The serine/threonine kinase tumor progression locus 2 (Tpl2, also known as Map3k8/Cot) is a potent inflammatory mediator that drives the production of TNF\u03b1, IL-1\u03b2, and IFN\u03b3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27261457", "endSection": "abstract" }, { "offsetInBeginSection": 1050, "offsetInEndSection": 1217, "text": "show that the MAP3K8 called Tpl2 was expressed in adipocytes and that IL-1beta and TNF-alpha activated Tpl2 and regulated its expression through an IKKbeta pathway. Ph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808894", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 939, "text": "We further examined the involvement of EPAC (exchange protein directly activated by cAMP) and TPL2 (tumor progression locus 2, MAP3K8) and found that inhibitors for EPAC and TPL2 reduced AR agonist-induced IL-1\u03b2 reporter activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32253104", "endSection": "abstract" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1382, "text": "found that another major mechanism for the TPL2 contribution to NOD2 signalling was through ERK-dependent and JNK-dependent caspase-1 and caspase-8 activation, which in turn, led to early autocrine interleukin (IL)-1\u03b2 and IL-18 secretion and amplification of long-term cytokines. Im", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26215868", "endSection": "abstract" }, { "offsetInBeginSection": 794, "offsetInEndSection": 950, "text": "Additionally, high mRNA expression levels of IL-1\u03b2, IL-6 and IL-8, but not TNF -\u03b1, in human adipose tissue were associated with higher expression of MAP3K8.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586913", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1347, "text": "Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1\u03b2, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24586913", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1456, "text": "In contrast to the cell-type- and receptor-specific regulation of TNF, we found that Tpl2 is essential for IL-1beta production from both macrophages and dendritic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19933865", "endSection": "abstract" } ] }, { "body": "Which company produces the Oncomine Dx target test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31349061" ], "ideal_answer": [ "The Oncomine Dx Target Test Panel is produced by Thermo Fisher Scientific." ], "exact_answer": [ "Thermo Fisher Scientific" ], "type": "factoid", "id": "606bfe5b94d57fd879000073", "snippets": [ { "offsetInBeginSection": 632, "offsetInEndSection": 991, "text": "All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31349061", "endSection": "abstract" } ] }, { "body": "Describe the INSPEcT R package", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25957348" ], "ideal_answer": [ "INSPEcT is a computational tool to infer mRNA synthesis, processing and degradation dynamics from RNA- and 4sU-seq time course experiments.", "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. INSPEcT provides gene-level quantification of these rates, and a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations. Software performance is tested on a synthetic dataset, instrumental to guide the choice of the modeling parameters and the experimental design.", "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. INSPECT provides gene-level quantification of these rates, and a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations. Software performance is tested on a synthetic dataset, instrumental to guide the choice of the modeling parameters and the experimental design.", "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. In addition, it provides gene-level quantification of these rates, and a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations.", "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation.", "InSPEcT is an R package for the integrative analysis of RNA-seq data to study the dynamics of transcriptional regulation.", "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. To graphically inspect the resulting networks, the package contains a visualization tool, which allows for the direct network manipulation and access of node and link information. INSPecT-GUI is freely available within the R/Bioconductor package INSPECT at http://bioconductor.org/packages/INSPECAT/.", "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. In particular, it provides a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations. Software performance is tested on a synthetic dataset, instrumental to guide the choice of the modeling parameters and the experimental design." ], "type": "summary", "id": "603256981cb411341a00013c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "INSPEcT: a computational tool to infer mRNA synthesis, processing and degradation dynamics from RNA- and 4sU-seq time course experiments.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25957348", "endSection": "title" }, { "offsetInBeginSection": 419, "offsetInEndSection": 899, "text": "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. INSPEcT provides gene-level quantification of these rates, and a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations. Software performance is tested on a synthetic dataset, instrumental to guide the choice of the modeling parameters and the experimental design.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25957348", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by Teprotumumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30575804", "http://www.ncbi.nlm.nih.gov/pubmed/29273685", "http://www.ncbi.nlm.nih.gov/pubmed/31377284", "http://www.ncbi.nlm.nih.gov/pubmed/31813786", "http://www.ncbi.nlm.nih.gov/pubmed/30385883", "http://www.ncbi.nlm.nih.gov/pubmed/25105999", "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "http://www.ncbi.nlm.nih.gov/pubmed/33221815", "http://www.ncbi.nlm.nih.gov/pubmed/32088116", "http://www.ncbi.nlm.nih.gov/pubmed/32040069", "http://www.ncbi.nlm.nih.gov/pubmed/32059832", "http://www.ncbi.nlm.nih.gov/pubmed/32157641", "http://www.ncbi.nlm.nih.gov/pubmed/31814726", "http://www.ncbi.nlm.nih.gov/pubmed/30215690", "http://www.ncbi.nlm.nih.gov/pubmed/32429706", "http://www.ncbi.nlm.nih.gov/pubmed/26361263", "http://www.ncbi.nlm.nih.gov/pubmed/32707005", "http://www.ncbi.nlm.nih.gov/pubmed/31971679", "http://www.ncbi.nlm.nih.gov/pubmed/31356255", "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "http://www.ncbi.nlm.nih.gov/pubmed/28467880", "http://www.ncbi.nlm.nih.gov/pubmed/29744034", "http://www.ncbi.nlm.nih.gov/pubmed/32795835", "http://www.ncbi.nlm.nih.gov/pubmed/33237667" ], "ideal_answer": [ "Teprotumumab is a human monoclonal antibody that targets IGF-1R. It can be used for treatment of thyroid eye disease." ], "exact_answer": [ "IGF-1R" ], "type": "factoid", "id": "6024a4111cb411341a0000a2", "snippets": [ { "offsetInBeginSection": 823, "offsetInEndSection": 966, "text": "Teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) has been investigated in a trial, showing it was very effective in GO patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31813786", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 741, "text": "METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31971679", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 488, "text": "Furthermore, an IGF-IR inhibitor, teprotumumab, has emerged from 2 clinical trials as a promising treatment for active, moderate to severe TAO. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32040069", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 958, "text": "Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) showed to be very effective in GO patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32059832", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 728, "text": "RT OPINION: Teprotumumab is a human monoclonal antibody targeting insulin-like growth factor-I receptor. Cli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32707005", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 254, "text": "Teprotumumab is a human insulin-like growth factor-I receptor monoclonal inhibitor antibody which indicated for treating thyroid eye disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32707005", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1214, "text": "cent completion of phase 2 and 3 randomized, placebo-controlled trials demonstrate the efficacy and safety of teprotumumab, a fully human monoclonal IGF-1R antagonist antibody, in patients with moderate-to-severe, active TED. Both ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31377284", "endSection": "abstract" }, { "offsetInBeginSection": 611, "offsetInEndSection": 837, "text": "Recent advances in the understanding of the molecular basis of TED have facilitated the development of targeted molecular therapies such as teprotumumab, an insulin-like growth factor-1 receptor inhibiting monoclonal antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31814726", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 836, "text": "he most promising results are observed with small thyroid stimulating hormone receptor molecules interacting with the receptor on thyrocytes and fibroblasts and with the anti-IGF-1 receptor antibody teprotumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25105999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "TSH-Mediated TNF\u03b1 Production in Human Fibrocytes Is Inhibited by Teprotumumab, an IGF-1R Antagonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "endSection": "title" }, { "offsetInBeginSection": 1391, "offsetInEndSection": 1564, "text": "These observations served as the rationale for implementing a recently completed therapeutic trial of teprotumumab, a monoclonal inhibitory antibody targeting IGF-IR in TAO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30215690", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1495, "text": "ting downstream of IGF1-R, sirolimus may offer a cost-effective alternative to teprotumumab therapy. Clin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33237667", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 957, "text": "Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) showed to be very effective in GO patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32059832", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 703, "text": " Teprotumumab (TMB) is a human monoclonal IGF-1R blocking antibody currently in clinical trial for GO and inhibits TSHR-mediated actions in FCs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26087256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Teprotumumab (teprotumumab-trbw; TEPEZZA\u2122 - Horizon Therapeutics) is a monoclonal antibody insulin-like growth factor-I receptor (IGF-IR) antagonist developed for the treatment of thyroid eye disease (Graves ophthalmopathy/orbitopathy, thyroid-associated ophthalmopathy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32157641", "endSection": "abstract" }, { "offsetInBeginSection": 733, "offsetInEndSection": 903, "text": "Most promising results are obtained by interacting with the PIK3/mTORC1 signaling cascades for adipogenesis and the anti-IGF-1R with the monoclonal antibody teprotumumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26361263", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 505, "text": " Teprotumumab (RV 001, R1507) is a human monoclonal anti-IGF-1R blocking antibody currently undergoing a phase 2 clinical trial in patients with active TAO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 1366, "offsetInEndSection": 1567, "text": "A recently completed therapeutic trial of teprotumumab, a human IGF1R inhibiting antibody, in patients with moderate to severe, active TAO, indicates the potential effectiveness and safety of the drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29273685", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1019, "text": "Teprotumumab is a monoclonal antibody directed against the IGF-1R that was FDA-approved in 2020 for the treatment of Graves' orbitopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32795835", "endSection": "abstract" }, { "offsetInBeginSection": 982, "offsetInEndSection": 1213, "text": "ecent completion of phase 2 and 3 randomized, placebo-controlled trials demonstrate the efficacy and safety of teprotumumab, a fully human monoclonal IGF-1R antagonist antibody, in patients with moderate-to-severe, active TED. Both", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31377284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1 action in fibrocytes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "title" }, { "offsetInBeginSection": 616, "offsetInEndSection": 709, "text": "GN: Fibrocytes were treated without or with teprotumumab in combination with IGF-1 or TSH.MAI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 967, "offsetInEndSection": 1102, "text": " Fibrocyte display of IGF-1R and TSHR was reduced with teprotumumab, as were IGF-1- and TSH-dependent phosphorylated Akt levels. TSH in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 1198, "offsetInEndSection": 1282, "text": "S: Teprotumumab attenuates the actions of both IGF-1 and TSH in fibrocytes. Specific", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24878056", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 233, "text": "Teprotumumab, a blocking antibody to the insulin like growth factor 1 receptor (IGF-1R) has been shown to significantly reduce proptosis in recent phase 2 and 3 trials in patients with inflammatory thyroid eye disease (TED).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33221815", "endSection": "abstract" }, { "offsetInBeginSection": 1569, "offsetInEndSection": 1735, "text": " findings demonstrate for the first time, that teprotumumab, a blocking antibody to the IGF-1R reduces proptosis in a series of patients with non-inflammatory TED. Ov", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33221815", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 675, "text": "Teprotumumab, a monoclonal IGF-1R antagonist, has demonstrated previously in a 24 week, randomized, controlled trial to produce significant changes in composite outcomes of proptosis and clinical activity score as compared with placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30575804", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30575804", "endSection": "title" }, { "offsetInBeginSection": 99, "offsetInEndSection": 448, "text": "ar condition. Teprotumumab is a human insulin-like growth factor-I receptor monoclonal inhibitor antibody which indicated for treating thyroid eye disease.AREAS COVERED: The authors performed a systematic review of the literature using the PubMed database, and the following keywords were used: 'teprotumumab,' 'thyroid eye disease,' and 'insulin-li", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32707005", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 648, "text": "y concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy.METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28467880", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1396, "text": " In addition, targeted biologic therapies have shown promise, including teprotumumab (anti-IGFR) which appears to substantially reduce proptosis, rituximab (anti-CD20) which reduces inflammation and tocilizumab (anti-IL-6) which potentially benefits both of these parameters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31356255", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 617, "text": "Teprotumumab (Tepezza) is a human monoclonal antibody against the insulin-like growth factor type I receptor (IGF-IR), recently evaluated in two clinical trials for active moderate-to-severe TAO that was recently approved by the United States Food and Drug Administration (FDA) for use in TAO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32429706", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 854, "text": " Despite these challenges, several agents, most developed for treatment of other diseases, have found their way into consideration for use in active TAO through repurposing. Among these, teprotumumab is a fully human inhibitory monoclonal antibody against the insulin-like growth factor I receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32088116", "endSection": "abstract" }, { "offsetInBeginSection": 912, "offsetInEndSection": 1130, "text": "Results from a very recently published clinical trial assessing the safety and efficacy of teprotumumab, an inhibitory human anti-IGF-IR monoclonal antibody, in active, moderate to severe TAO are extremely encouraging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29744034", "endSection": "abstract" } ] }, { "body": "Which protein is encoded by the protein APOBEC3C?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33193411", "http://www.ncbi.nlm.nih.gov/pubmed/30431097", "http://www.ncbi.nlm.nih.gov/pubmed/31664825", "http://www.ncbi.nlm.nih.gov/pubmed/31519749", "http://www.ncbi.nlm.nih.gov/pubmed/32345636" ], "ideal_answer": [ "The gene APOBEC3C codes for: apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C" ], "exact_answer": [ "apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C" ], "type": "factoid", "id": "607323fe94d57fd879000079", "snippets": [ { "offsetInBeginSection": 152, "offsetInEndSection": 343, "text": "apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; shortened here to A3), act by deaminating cytidines to uridines during the reverse transcription reaction of HIV-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32345636", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 827, "text": "apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33193411", "endSection": "abstract" }, { "offsetInBeginSection": 940, "offsetInEndSection": 1006, "text": "apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC)3A,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30431097", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1079, "text": "apolipoprotein B mRNA-editing enzyme catalytic subunit 3C (APOBEC3C, a nucleic acid-editing deaminase)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31519749", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 514, "text": " APOBEC3C (apolipoprotein-B mRNA-editing catalytic polypeptide-like 3C (A3C))", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31664825", "endSection": "abstract" } ] }, { "body": "Does AZD3759 cross the blood brain barrier?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "http://www.ncbi.nlm.nih.gov/pubmed/29430654", "http://www.ncbi.nlm.nih.gov/pubmed/29056570", "http://www.ncbi.nlm.nih.gov/pubmed/28625644", "http://www.ncbi.nlm.nih.gov/pubmed/26898616" ], "ideal_answer": [ "AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier.", "AZD3759 is an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration.", "Yes, AZD3759 cross the blood brain barrier." ], "exact_answer": "yes", "type": "yesno", "id": "5e67cd6b1af46fc13000001e", "snippets": [ { "offsetInBeginSection": 97, "offsetInEndSection": 201, "text": "AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29430654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "endSection": "title" }, { "offsetInBeginSection": 630, "offsetInEndSection": 779, "text": "We report the discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 305, "text": "AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056570", "endSection": "abstract" }, { "offsetInBeginSection": 630, "offsetInEndSection": 863, "text": "We report the discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1229, "text": "Another promising class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26898616", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 304, "text": "AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056570", "endSection": "abstract" }, { "offsetInBeginSection": 62, "offsetInEndSection": 301, "text": "In our study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29430654", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1241, "text": "sing class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases. Acquired re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26898616", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 880, "text": " discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue. Treatment with A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "endSection": "title" }, { "offsetInBeginSection": 65, "offsetInEndSection": 312, "text": "our study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC. Besides, t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29430654", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1221, "text": " in patients with BM and LM treated with AZD3759 confirms its BBB-penetrant properties and antitumor activities. Our data demonstrate ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "endSection": "abstract" }, { "offsetInBeginSection": 3432, "offsetInEndSection": 3584, "text": "ood penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further assessment of this compound in studies.FUNDI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056570", "endSection": "abstract" }, { "offsetInBeginSection": 899, "offsetInEndSection": 1194, "text": "The next generation EGFR TKIs osimertinib and AZD3759 have improved BBB penetration and the BLOOM study of osimertinib and AZD3759 has reported highly promising intracranial efficacy and may herald a new frontier to treat this therapeutically challenging subset of advanced EGFR mutant patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28625644", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1319, "text": "The results showed the BBB penetration of AZD3759 was decreased within 24 hr after radiation, however, the free concentration of AZD3759 in brain kept at a high level in the context of radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29430654", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1123, "text": "We also detected the BBB penetration of AZD3759 when combined with cranial radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29430654", "endSection": "abstract" }, { "offsetInBeginSection": 3430, "offsetInEndSection": 3583, "text": " good penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further assessment of this compound in studies.FUND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056570", "endSection": "abstract" }, { "offsetInBeginSection": 3380, "offsetInEndSection": 3544, "text": "n pretreated with a tyrosine kinase inhibitor. The good penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further asse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29056570", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1199, "text": "An early clinical study in patients with BM and LM treated with AZD3759 confirms its BBB-penetrant properties and antitumor activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27928026", "endSection": "abstract" } ] }, { "body": "What is the major sequence determinant for nucleosome positioning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20232936", "http://www.ncbi.nlm.nih.gov/pubmed/19620965", "http://www.ncbi.nlm.nih.gov/pubmed/21551148", "http://www.ncbi.nlm.nih.gov/pubmed/22435808", "http://www.ncbi.nlm.nih.gov/pubmed/26305225", "http://www.ncbi.nlm.nih.gov/pubmed/17038564", "http://www.ncbi.nlm.nih.gov/pubmed/21206756", "http://www.ncbi.nlm.nih.gov/pubmed/30113318" ], "ideal_answer": [ "G+C content is the primary determinant of MNase-derived nucleosome occupancy." ], "exact_answer": [ "G+C content", "GC%" ], "type": "factoid", "id": "5fe3131ca43ad31278000048", "snippets": [ { "offsetInBeginSection": 252, "offsetInEndSection": 410, "text": "Many yeast promoter and terminator regions intrinsically disfavor nucleosome formation, and nucleosomes assembled in vitro show strong rotational positioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19620965", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 686, "text": "Sequence analysis of 284,091 putative nucleosome cores obtained in this manner from a mixed-stage population of C. elegans reveals a combined picture of flexibility and constraint in nucleosome positioning", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17038564", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 371, "text": "Nucleosome positioning influences the overall rate of sequence evolution. However, its impacts on specific patterns of sequence evolution are still poorly understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21551148", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 528, "text": "his strongly affects nucleosome positioning data and especially sequence-dependent models for nucleosome positioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21206756", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 589, "text": "e argue that, in budding yeast, while DNA sequence-specified nucleosome positioning may contribute to positions flanking the regions lacking nucleosomes, DNA thermodynamic stability is a major component determinant of the genetic organization of this organism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22435808", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 906, "text": "DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26305225", "endSection": "abstract" }, { "offsetInBeginSection": 325, "offsetInEndSection": 607, "text": "This paper rigorously quantifies the contribution of hitherto-debated sequence features-including G+C content, 10.5\u2009bp periodicity, and poly(dA:dT) tracts-to three distinct aspects of genome-wide nucleosome landscape: occupancy, translational positioning and rotational positioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30113318", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1276, "text": "We further show that the 10.5\u2009bp nucleotide periodicity facilitates rotational but not translational positioning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30113318", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1161, "text": "We find that although G+C content is the primary determinant of MNase-derived nucleosome occupancy, MNase digestion biases may substantially influence this GC dependence. By contrast, poly(dA:dT) tracts are seen to deter nucleosome formation, regardless of the experimental method used", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30113318", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 889, "text": "we consider the anisotropic flexibility of pyrimidine-purine (YR) dimeric steps in the context of their neighbors (e.g., YYRR versus RYRY); (iii) we postulate that alternating AT-rich and GC-rich motifs reflect sequence-dependent interactions between histone arginines and DNA in the minor groove.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20232936", "endSection": "abstract" } ] }, { "body": "Which is the primary enzyme metabolizing esomeprazole?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32227647" ], "ideal_answer": [ "Esomeprazole is primarily metabolized by CYP2C19." ], "exact_answer": [ "CYP2C19" ], "type": "factoid", "id": "606ad16594d57fd879000051", "snippets": [ { "offsetInBeginSection": 368, "offsetInEndSection": 418, "text": "Esomeprazole is primarily metabolized by CYP2C19. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227647", "endSection": "abstract" } ] }, { "body": "Which factors contribute to the risk of very-early-onset inflammatory bowel disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33122718", "http://www.ncbi.nlm.nih.gov/pubmed/26836588", "http://www.ncbi.nlm.nih.gov/pubmed/32081864", "http://www.ncbi.nlm.nih.gov/pubmed/32941940" ], "ideal_answer": [ "Somalatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease, particularly atrial fibrillation and dysregulation of transcphenne muscular dystrophy, as well as other genetic variation, in the early phase of disease.", "Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.", "Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease (VEO-IBD).", "Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease. Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders.", "Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Somatic mosaicism and common genetic variation contribute to the risk of this disease.", "Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders including Crohn's disease, depression and cocaine addiction. Somatic mosaicism and common genetic variation contribute to the risk of IBD." ], "exact_answer": [ [ "Somatic mosaicism" ], [ "Common genetic variation" ] ], "type": "list", "id": "602822341cb411341a0000f8", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32081864", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1068, "text": "Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P\u2009<\u20094\u2009\u00d7\u200910-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P\u2009<\u20095\u2009\u00d7\u200910-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32081864", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Variants in TRIM22 That Affect NOD2 Signaling Are Associated With Very-Early-Onset Inflammatory Bowel Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26836588", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Excessive deubiquitination of NLRP3-R779C variant contributes to very-early-onset inflammatory bowel disease development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32941940", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Excessive deubiquitination of NLRP3-R779C variant contributes to very-early-onset inflammatory bowel disease development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32941940", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33122718", "endSection": "title" } ] }, { "body": "What disease is treated with BIVV001?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32078672", "http://www.ncbi.nlm.nih.gov/pubmed/32905674" ], "ideal_answer": [ "BIVV001 fusion protein has been developed as Factor VIII replacement therapy for hemophilia A" ], "exact_answer": [ "Hemophilia A" ], "type": "factoid", "id": "6020af2e1cb411341a000084", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "BIVV001, a new class of factor VIII replacement for hemophilia A that is independent of von Willebrand factor in primates and mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32078672", "endSection": "title" }, { "offsetInBeginSection": 541, "offsetInEndSection": 756, "text": "We have developed a new class of FVIII replacement, rFVIIIFc-VWF-XTEN (BIVV001), that is physically decoupled from endogenous VWF and has enhanced pharmacokinetic properties compared with all previous FVIII products", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32078672", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1557, "text": "BIVV001 is the first rFVIII with the potential to significantly change the treatment paradigm for severe hemophilia A by providing optimal protection against all bleed types, with less frequent doses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32078672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905674", "endSection": "title" }, { "offsetInBeginSection": 301, "offsetInEndSection": 533, "text": ". BIVV001 (rFVIIIFc-VWF-XTEN) is a novel fusion protein designed to overcome this half-life ceiling and maintain high sustained factor VIII activity levels. Data are lacking on the safety and pharmacokinetics of single-dose BIVV001.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905674", "endSection": "abstract" }, { "offsetInBeginSection": 2003, "offsetInEndSection": 2392, "text": "CONCLUSIONS: In a small, early-phase study involving men with severe hemophilia A, a single intravenous injection of BIVV001 resulted in high sustained factor VIII activity levels, with a half-life that was up to four times the half-life associated with recombinant factor VIII, an increase that could signal a new class of factor VIII replacement therapy with a weekly treatment interval.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32905674", "endSection": "title" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1556, "text": "BIVV001 is the first rFVIII with the potential to significantly change the treatment paradigm for severe hemophilia A by providing optimal protection against all bleed types, with less frequent doses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32078672", "endSection": "abstract" } ] }, { "body": "What is the mode of action of Thiazovivin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25490878", "http://www.ncbi.nlm.nih.gov/pubmed/28849097", "http://www.ncbi.nlm.nih.gov/pubmed/27647250" ], "ideal_answer": [ "Thiazovivin is a selective small molecule that directly targets Rho-associated kinase (ROCK) and increases expression of pluripotency factors." ], "exact_answer": [ "Thiazovivin is a selective small molecule that directly targets Rho-associated kinase (ROCK) and increases expression of pluripotency factors." ], "type": "factoid", "id": "606b2bf594d57fd87900005d", "snippets": [ { "offsetInBeginSection": 230, "offsetInEndSection": 404, "text": "This study aimed to investigate the effects of the novel Rho\u00a0associated coiled-coil containing protein kinase\u00a0(ROCK) inhibitor, thiazovivin\u00a0(2,4\u2011disubstituted thiazole, TZV),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28849097", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 73, "text": "thiazovivin, a novel ROCK inhibitor,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27647250", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1202, "text": "Thiazovivin is a selective small molecule that directly targets Rho-associated kinase (ROCK) and increases expression of pluripotency factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25490878", "endSection": "abstract" } ] }, { "body": "Explain the association between Barr bodies (nuclear inclusions) and the X chromosome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17477348", "http://www.ncbi.nlm.nih.gov/pubmed/17611545", "http://www.ncbi.nlm.nih.gov/pubmed/28374668", "http://www.ncbi.nlm.nih.gov/pubmed/15682788", "http://www.ncbi.nlm.nih.gov/pubmed/1524841", "http://www.ncbi.nlm.nih.gov/pubmed/12915472", "http://www.ncbi.nlm.nih.gov/pubmed/11438711", "http://www.ncbi.nlm.nih.gov/pubmed/25136351", "http://www.ncbi.nlm.nih.gov/pubmed/7828232", "http://www.ncbi.nlm.nih.gov/pubmed/27194855", "http://www.ncbi.nlm.nih.gov/pubmed/23542155", "http://www.ncbi.nlm.nih.gov/pubmed/21416650", "http://www.ncbi.nlm.nih.gov/pubmed/187357" ], "ideal_answer": [ "Barr body is an inactivated X chromosome in the normal female somatic cell.", "A Barr body (named after discoverer Murray Barr) is an inactive X chromosome in a cell with more than one X chromosome, rendered inactive in a process called lyonization, in species with XY sex-determination (including humans).", "Transcriptional inactivation of one X chromosome in mammalian female somatic cells leads to condensation of the inactive X chromosome into the heterochromatic sex chromatin, or Barr body.", "Barr body is an inactivated X chromosome in the normal female somatic cell" ], "type": "summary", "id": "601f0d6f1cb411341a00006f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Barr body is an inactivated X chromosome in the normal female somatic cell", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15682788", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 309, "text": " BBs are unique chromatin structures formed due to the condensation of the X-chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27194855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "There is a marked difference between the frequencies of neutrophil nuclear drumsticks and mucosal cell Barr bodies in any given woman despite the fact that both represent an inactivated X chromosome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7828232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Transcriptional inactivation of one X chromosome in mammalian female somatic cells leads to condensation of the inactive X chromosome into the heterochromatic sex chromatin, or Barr body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11438711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "There is a marked difference between the frequencies of neutrophil nuclear drumsticks and mucosal cell Barr bodies in any given woman despite the fact that both represent an inactivated X chromosome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7828232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Interest has recently reawakened in whether loss of the heterochromatic X chromosome (Barr body) is prevalent in certain breast and ovarian cancers, and new insights into the mechanisms involved have emerged.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17611545", "endSection": "abstract" }, { "offsetInBeginSection": 368, "offsetInEndSection": 526, "text": "The centromeres of inactive X chromosomes (Barr bodies) were located closer to the nuclear periphery as compared with the centromeres of active X chromosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17477348", "endSection": "abstract" }, { "offsetInBeginSection": 580, "offsetInEndSection": 687, "text": "Long noncoding RNAs and polycomb repression act together to produce an inactive X chromosome, or Barr body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25136351", "endSection": "abstract" }, { "offsetInBeginSection": 1471, "offsetInEndSection": 1711, "text": " Barr bodies of characteristic drumstick appearance bearing inactive X chromosome in interphase nuclei of mature granulocytes in fertile female patients exhibited a heterochromatin condensation state similar to nuclear segments. This hetero", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28374668", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "There is a marked difference between the frequencies of neutrophil nuclear drumsticks and mucosal cell Barr bodies in any given woman despite the fact that both represent an inactivated X chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7828232", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 623, "text": "of the clusters located near the nuclear membrane where inactive X chromatins (Barr-bodies) were usually found. The m", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1524841", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 533, "text": "ntromeres of inactive X chromosomes (Barr bodies) were located closer to the nuclear periphery as compared with the centromeres of active X chromosomes. In add", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17477348", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 301, "text": "This observation suggests that the condensation of the X chromosome in the form of Barr bodies depends on the level of endogen cyclic AMP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/187357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12915472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Barr body is an inactivated X chromosome in the normal female somatic cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15682788", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "The Barr body is the inactive X chromosome in a female somatic cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21416650", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 308, "text": " BBs are unique chromatin structures formed due to the condensation of the X-chromosome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27194855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Chromatin of the Barr body: histone and non-histone proteins associated with or excluded from the inactive X chromosome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12915472", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Human inactive X chromosome (Xi) forms a compact structure called the Barr body, which is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23542155", "endSection": "abstract" } ] }, { "body": "Is the zelda transcription factor a chromatin remodeller?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "http://www.ncbi.nlm.nih.gov/pubmed/10809665", "http://www.ncbi.nlm.nih.gov/pubmed/28287392", "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "http://www.ncbi.nlm.nih.gov/pubmed/26335633", "http://www.ncbi.nlm.nih.gov/pubmed/23560912", "http://www.ncbi.nlm.nih.gov/pubmed/30518940", "http://www.ncbi.nlm.nih.gov/pubmed/28676122", "http://www.ncbi.nlm.nih.gov/pubmed/30993896", "http://www.ncbi.nlm.nih.gov/pubmed/27879204", "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "http://www.ncbi.nlm.nih.gov/pubmed/27599465", "http://www.ncbi.nlm.nih.gov/pubmed/22247430" ], "ideal_answer": [ "During developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome. Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation. Early enhancers are characterized by an intrinsically high nucleosome barrier. Zelda tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of zelda(zld) motifs.", "Yes, it is known as a chromatin remodeling factor.", "Yes, the zebrafish transcription factor Zelda is a chromatin remodeling factor.", "Yes, it is known as a transcription factor for a chromatin remodeling factor.", "Yes, the zelda transcription factor is a chromatin remodller.", "Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo. Zelda is essential for hundreds of regions of open chromatin. Zelda binds cis-regulatory elements (TAGteam heptamers), making chromatin accessible for gene transcription.", "This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression." ], "exact_answer": "yes", "type": "yesno", "id": "5fe0c141a43ad31278000035", "snippets": [ { "offsetInBeginSection": 502, "offsetInEndSection": 648, "text": "ncreasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30518940", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1103, "text": "Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30518940", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 382, "text": "Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335633", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335633", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 660, "text": "early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "title" }, { "offsetInBeginSection": 425, "offsetInEndSection": 538, "text": "Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcriptio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 424, "text": "During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1297, "text": "Zld facilitates binding of Dl to regulatory DNA, and that this is associated with increased chromatin accessibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "endSection": "abstract" }, { "offsetInBeginSection": 1298, "offsetInEndSection": 1402, "text": "Importantly, the change in chromatin accessibility is strongly correlated with the change in Zld binding", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "title" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1451, "text": "We propose that both Zelda and GAGA factor function to specify sites of open chromatin and together facilitate the remodeling of the early embryonic genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1577, "text": "is analysis highlighted a strong and specific enrichment of predicted ZGA-associated CRMs for Zelda, CBP, Trl binding sites, as well as for histone marks associated with active enhancers (H3K4me1) and for open chromatin regions.CO", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23560912", "endSection": "abstract" }, { "offsetInBeginSection": 813, "offsetInEndSection": 894, "text": "We demonstrate that Zelda is essential for hundreds of regions of open chromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 508, "text": "Intriguingly, some Zelda sites still maintain these chromatin patterns in Drosophila embryos lacking maternal Zelda protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676122", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Zelda potentiates morphogen activity by increasing chromatin accessibility.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 247, "text": "Zelda binds cis-regulatory elements (TAGteam heptamers), making chromatin accessible for gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30993896", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 385, "text": "zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility. D. mela", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "endSection": "abstract" }, { "offsetInBeginSection": 895, "offsetInEndSection": 1010, "text": "This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 218, "offsetInEndSection": 582, "text": "While analyzing chromatin immunoprecipitation data sets from 21 sequence-specific transcription factors active in the Drosophila embryo, we found that binding of all factors exhibits a dose-dependent relationship with \"TAGteam\" sequence motifs bound by the zinc finger protein Vielfaltig, also known as Zelda, a recently discovered activator of the zygotic genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247430", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1110, "text": "These different timing classes each associate with binding sites for two transcription factors, GAGA-factor and Zelda, previously implicated in controlling chromatin accessibility at ZGA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27879204", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1162, "text": "Together this reveals a distinct requirement for a chromatin remodeller in promoting the activity of the pioneer factor OCT4 and regulating the pluripotency network.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287392", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 834, "text": "Chromatin accessibility at OCT4-bound sites requires the chromatin remodeller BRG1, which is recruited to these sites by OCT4 to support additional transcription factor binding and expression of the pluripotency-associated transcriptome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287392", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287392", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development and cellular reprogramming.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287392", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 389, "text": "During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet it remains unclear how different pioneer factors achieve this.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287392", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 596, "text": "Here, we discover that the pluripotency-associated pioneer factor OCT4 binds chromatin to shape accessibility, transcription factor co-binding, and regulatory element function in mouse embryonic stem cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28287392", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 540, "text": "Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1186, "text": "Unexpectedly, chromatin at a large subset of Zelda-bound regions remains open even in the absence of Zelda.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 262, "text": "During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 653, "offsetInEndSection": 812, "text": "Here we used formaldehyde-assisted isolation of regulatory elements to determine the role of Zelda in regulating regions of open chromatin in the early embryo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30518940", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 383, "text": "Recently, we showed that Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28676122", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 377, "text": "The zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28671979", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 652, "text": "Nonetheless, the extent to which Zelda influences chromatin accessibility across the genome is largely unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26335634", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1297, "text": "We present evidence that Zld facilitates binding of Dl to regulatory DNA, and that this is associated with increased chromatin accessibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24909324", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 308, "text": "ZRF1 facilitates the remodeling of multiprotein complexes at chromatin and lies at the heart of signaling processes that occur at DNA damage sites and during transcriptional activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27599465", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 750, "text": "We postulate that ZRF1 operates in conjunction with cellular remodeling machines and suggest that on-site remodeling might be a hallmark of many chromatin-associated signaling pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27599465", "endSection": "abstract" }, { "offsetInBeginSection": 360, "offsetInEndSection": 529, "text": "Reconstituted transcription reactions established that the Brahma (BRM) chromatin-remodeling complex is essential for Zeste-directed activation on nucleosomal templates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10809665", "endSection": "abstract" } ] }, { "body": "What is the effect of the alleles CYP2C19*2 and CYP2C19*3 on CYP2C19 function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32029306" ], "ideal_answer": [ "The CYP2C19*2 and CYP2C19*3 alleles of CYP2C19 are associated with loss-of-function (LOF)." ], "type": "summary", "id": "606ad1f094d57fd879000052", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "The CYP2C19*2 or *3 loss-of-function (LOF) allele is associated with high platelet reactivity (HPR) on clopidogrel treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32029306", "endSection": "abstract" } ] }, { "body": "Describe Full Spectrum of Intolerance to Loss-of-function (FUSIL)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32005800" ], "ideal_answer": [ "Full Spectrum of Intolerance to Loss-of-function (FUSIL) is a cross-species gene classification across the full spectrum of mutations in genes of unknown function. FUSIL has been proposed as a method to identify potentially pathogenic variants in genes not previously associated with rare diseases.", "The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. By integrating measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines, a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) was proposed. Genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development.", "The FUSIL is the Full Spectrum of Intolerance to Loss-of-function (FUSIL). It's the full spectrum of genes that are not essential for cell survival, but essential for organism development.", "Full Spectrum of Intolerance to Loss-of-function (FUSIL) is a cross-species gene classification across the full spectrum of genes in five mutually exclusive categories have differing biological properties. FUSIL is proposed as an efficient approach for disease gene discovery.", "Full Spectrum of Intolerance to Loss-of-function (FUSIL) is a cross-species gene classification across the full spectrum of essential and non-essential genes. FUSIL is an efficient approach for disease gene discovery." ], "type": "summary", "id": "6028f6781cb411341a000100", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1127, "text": "The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32005800", "endSection": "abstract" } ] }, { "body": "Is capmatinib effective for glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31776899" ], "ideal_answer": [ "No. Combination of capmatinib buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma." ], "exact_answer": "no", "type": "yesno", "id": "6025db0e1cb411341a0000b8", "snippets": [ { "offsetInBeginSection": 1501, "offsetInEndSection": 1636, "text": "CONCLUSION: The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776899", "endSection": "abstract" } ] }, { "body": "Are there antimicrobial proteins in royal jelly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33151599", "http://www.ncbi.nlm.nih.gov/pubmed/31862270", "http://www.ncbi.nlm.nih.gov/pubmed/31936187", "http://www.ncbi.nlm.nih.gov/pubmed/32627752" ], "ideal_answer": [ "Yes,\nJelleines, isolated as novel antibacterial peptides from the Royal Jelly (RJ) of bees, exhibit broad-spectrum protection against microbial infections." ], "exact_answer": "yes", "type": "yesno", "id": "6057151094d57fd879000027", "snippets": [ { "offsetInBeginSection": 715, "offsetInEndSection": 857, "text": "Jellein, a peptide derived from royal jelly of honeybee has been shown to have promising effect against several bacterial and fungal species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31862270", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 654, "text": "It is also the most studied bee product, aimed at unravelling its bioactivities, such as antimicrobial, antioxidant, anti-aging, immunomodulatory, and general tonic action against laboratory animals, microbial organisms, farm animals, and clinical trials", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31936187", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 686, "text": "Jelleines, isolated as novel antibacterial peptides from the Royal Jelly (RJ) of bees, exhibit broad-spectrum protection against microbial infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32627752", "endSection": "abstract" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1586, "text": "The study showed significant antimicrobial activity from several proteins present in the honey of M. beecheii.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33151599", "endSection": "abstract" } ] }, { "body": "What are the years of the initiation and completion of the Human Genome project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12046269", "http://www.ncbi.nlm.nih.gov/pubmed/27087232", "http://www.ncbi.nlm.nih.gov/pubmed/30546257", "http://www.ncbi.nlm.nih.gov/pubmed/26952518", "http://www.ncbi.nlm.nih.gov/pubmed/10418432", "http://www.ncbi.nlm.nih.gov/pubmed/29068423", "http://www.ncbi.nlm.nih.gov/pubmed/11261244" ], "ideal_answer": [ "The Human Genome Project was initiated in 1990 and completed in 2003.", "The Human Genome Project (HGP) was initiated in 1990, and the completion of the genome project was in 2003." ], "exact_answer": [ [ "1990" ], [ "2003" ] ], "type": "list", "id": "601d72c21cb411341a000038", "snippets": [ { "offsetInBeginSection": 296, "offsetInEndSection": 616, "text": "In a bid to demystify the workings of the genome, the Human Genome Project (HGP) was initiated in 1990, with the chief goal of sequencing the approximately 3\u2009billion nucleotide base pairs of the human DNA. Since its completion in 2003, the HGP has opened new avenues for the application of genomics in clinical practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30546257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The human genome project (HGP) began in 1990 with a projected completion time of 15 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12046269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "The Human Genome Project (HGP) was initiated in 1990 and completed in 2003.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26952518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Information obtained from the Human Genome Project, initiated in 1990 and targeted for completion in 2005, will influence both health care and nursing practice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10418432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The Human Genome Project (HGP) was initiated in 1990 and completed in 2003. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26952518", "endSection": "abstract" }, { "offsetInBeginSection": 304, "offsetInEndSection": 512, "text": " to demystify the workings of the genome, the Human Genome Project (HGP) was initiated in 1990, with the chief goal of sequencing the approximately 3\u2009billion nucleotide base pairs of the human DNA. Since its ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30546257", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 392, "text": "nce the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29068423", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Since the completion of the Human Genome Project in 2003 and the announcement of the Precision Medicine Initiative by U.S.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27087232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Information obtained from the Human Genome Project, initiated in 1990 and targeted for completion in 2005, will influence both health care and nursing practice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10418432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "The human genome project was officially launched in 1990.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11261244", "endSection": "abstract" } ] }, { "body": "Which methods infer 3D genome structure without proximity ligation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28273065", "http://www.ncbi.nlm.nih.gov/pubmed/30150754", "http://www.ncbi.nlm.nih.gov/pubmed/29148971", "http://www.ncbi.nlm.nih.gov/pubmed/29887377", "http://www.ncbi.nlm.nih.gov/pubmed/30109602", "http://www.ncbi.nlm.nih.gov/pubmed/31848476", "http://www.ncbi.nlm.nih.gov/pubmed/24051548", "http://www.ncbi.nlm.nih.gov/pubmed/29401453", "http://www.ncbi.nlm.nih.gov/pubmed/25887659" ], "ideal_answer": [ "SPRITE is a method that enables genome-wide detection of higher-order interactions within the nucleus.\nTransposase-mediated analysis of chromatin looping (Trac-looping) for simultaneous detection of multiscale genome-wide chromatin interactions among regulatory elements and chromatin accessibility.\nGenome architecture mapping (GAM) can be used for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections.", "To investigate three-dimensional (3D) genome organization in prokaryotic and eukaryotic cells, three main strategies are employed, namely nuclear proximity ligation-based methods, imaging tools (such as fluorescence in situ hybridization (FISH) and its derivatives), and computational/visualization methods.", "Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype. By combining 3C and high-throughput sequencing, the Hi-C method reveals genome-wide interactions within topological domains and global genome structure as a whole. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. We describe a genome architecture assay, tethered multiple 3C (TM3C), that maps genome-wide chromatin contacts via a simple protocol of restriction enzyme digestion and religation of fragments upon agarose gel beads followed by paired-end sequencing. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We now report transposase-mediated analysis of chromatin looping (Trac-looping) for simultaneous detection of multiscale genome-wide chromatin interactions among regulatory elements and chromatin accessibility.", "Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype. By combining 3C and high-throughput sequencing, the Hi-C method reveals genome-wide interactions within topological domains and global genome structure as a whole. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. We describe a genome architecture assay, tethered multiple 3C (TM3C), that maps genome-wide chromatin contacts via a simple protocol of restriction enzyme digestion and religation of fragments upon agarose gel beads followed by paired-end sequencing. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles." ], "exact_answer": [ [ "SPRITE", "Split-pool recognition of interactions by tag extension" ], [ "Trac-looping", "Transposase-mediated analysis of chromatin looping" ], [ "Genome Architecture Mapping", "GAM" ] ], "type": "list", "id": "5ea97bec0d431b5f73000007", "snippets": [ { "offsetInBeginSection": 413, "offsetInEndSection": 855, "text": " Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29887377", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 766, "text": "Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24051548", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 321, "text": "We now report transposase-mediated analysis of chromatin looping (Trac-looping) for simultaneous detection of multiscale genome-wide chromatin interactions among regulatory elements and chromatin accessibility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30150754", "endSection": "abstract" }, { "offsetInBeginSection": 454, "offsetInEndSection": 618, "text": "By combining 3C and high-throughput sequencing, the Hi-C method reveals genome-wide interactions within topological domains and global genome structure as a whole. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30109602", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 553, "text": "Here we present a maximum-entropy model that is able to predict a contact map representation of structure given a sequence of bound factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29401453", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 729, "text": "We describe a genome architecture assay, tethered multiple 3C (TM3C), that maps genome-wide chromatin contacts via a simple protocol of restriction enzyme digestion and religation of fragments upon agarose gel beads followed by paired-end sequencing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25887659", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 436, "text": " Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28273065", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 845, "text": "Improvements to these methods and the recent development of ligation-free approaches, including GAM, SPRITE and ChIA-Drop, are now helping to uncover new aspects of 3D genome topology that confirm the nucleus to be a complex, highly organized organelle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31848476", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 855, "text": "Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29887377", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 589, "text": "Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29887377", "endSection": "abstract" } ] }, { "body": "How many genes are screened by the FoundationOne companion diagnostic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32504034" ], "ideal_answer": [ "FoundationOne CDx comprises a 324-gene panel." ], "exact_answer": [ "324" ], "type": "factoid", "id": "606b7e5694d57fd879000070", "snippets": [ { "offsetInBeginSection": 324, "offsetInEndSection": 543, "text": "In this study, we analyzed the clinicopathologic characteristics and comprehensive genomic profiling of 18 patients with pure triple-negative apocrine carcinomas (TNACs) using a 324-gene panel assay (FoundationOne CDx).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32504034", "endSection": "abstract" } ] }, { "body": "Interaction of WDR5 with which gene has a critical role in pancreatic cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27320920" ], "ideal_answer": [ "Mechanistically, WDR5 functions to sustain proper execution of DNA replication in pancreatic ductal adenocarcinoma (PDAC) cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR5. It was indeed demonstrated that interaction with c-Myc is critical for this function.", "WDR5 is a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1-4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR", "WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc. Interaction of the oncoprotein transcription factor MYC with its chromatin cofactor WDR5 is essential for tumor maintenance. The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation", "Interaction of WDR5 with WDR4 and c-Myc is critical for the development of pancreatic cancer." ], "exact_answer": [ "c-Myc" ], "type": "factoid", "id": "603251f81cb411341a00013a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "In\u00a0Vivo Functional Platform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27320920", "endSection": "title" }, { "offsetInBeginSection": 191, "offsetInEndSection": 1078, "text": "We developed an unbiased and in\u00a0vivo target discovery approach to identify molecular vulnerabilities in low-passage and patient-derived PDAC xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1-4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR5. We indeed demonstrate that interaction with c-Myc is critical for this function. By showing that ATR inhibition mimicked the effects of WDR5 suppression, these data provide rationale to test ATR and WDR5 inhibitors for activity in this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27320920", "endSection": "abstract" } ] }, { "body": "Can thiotepa be recommended for treatment of osteosarcoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31838406", "http://www.ncbi.nlm.nih.gov/pubmed/24672280" ], "ideal_answer": [ "No. Thiotepa did not improve survival of patients with osteosarcoma and therefore can not be recommended for treatment of osteosarcoma." ], "exact_answer": "no", "type": "yesno", "id": "6025e2641cb411341a0000bb", "snippets": [ { "offsetInBeginSection": 1524, "offsetInEndSection": 1939, "text": "CONCLUSION: Adjuvant HDTp failed to significantly improve OS and PFS in resectable relapsed osteosarcomas. Despite a trend of prolonged survival and an acceptable toxicity, thiotepa cannot be recommended.KEY MESSAGE: HDTp and autologous transplantation added to SCT did not improve OS and PFS in patients with resectable relapsed osteosarcomas. Despite a trend of prolonged survival, thiotepa cannot be recommended.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31838406", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1449, "text": "Conclusion. The use of HD thiotepa and ASCT is feasible in patients with relapsed osteosarcoma. A randomized study for recurrent osteosarcoma between standard salvage chemotherapy and high dose thiotepa with stem cell rescue is ongoing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24672280", "endSection": "abstract" } ] }, { "body": "What is known about aberrant proteolytic activity in disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27079701", "http://www.ncbi.nlm.nih.gov/pubmed/24380647", "http://www.ncbi.nlm.nih.gov/pubmed/18710591", "http://www.ncbi.nlm.nih.gov/pubmed/18565216" ], "ideal_answer": [ "Research into Alzheimer's disease pathology and treatment has often focused on presenilin proteins. These proteins provide the key catalytic activity of the \u03b3-secretase complex in the cleavage of amyloid-\u03b2 precursor protein and resultant amyloid tangle deposition. Over the last 25 years, screening novel drugs to control this aberrant proteolytic activity has yet to identify effective treatments for the disease.\nOthers are human skin disorders where proteolytic pathways are dysregulated." ], "type": "summary", "id": "60571d4294d57fd879000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 414, "text": "Research into Alzheimer's disease pathology and treatment has often focused on presenilin proteins. These proteins provide the key catalytic activity of the \u03b3-secretase complex in the cleavage of amyloid-\u03b2 precursor protein and resultant amyloid tangle deposition. Over the last 25 years, screening novel drugs to control this aberrant proteolytic activity has yet to identify effective treatments for the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27079701", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 667, "text": "the authors report aberrant proteolytic activity in the salivary glands of non-obese diabetic mice and the generation of a unique organ-specific 17 kDa fragment of the chemokine and adhesion molecule fractalkine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18710591", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 830, "text": "survey the different roles of proteases in epidermal homeostasis (from processing enzymes to signalling molecules) and explore the spectrum of rare and common human skin disorders where proteolytic pathways are dysregulated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24380647", "endSection": "abstract" }, { "offsetInBeginSection": 1777, "offsetInEndSection": 1992, "text": "These data indicate that aberrant proteolytic activity in the NOD SMG results in increased fractalkine cleavage and generation of a unique fractalkine fragment. This specific cleavage may contribute to autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18565216", "endSection": "abstract" } ] }, { "body": "Does a comet assay measure radiation induced mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22147573", "http://www.ncbi.nlm.nih.gov/pubmed/33198930", "http://www.ncbi.nlm.nih.gov/pubmed/10665958", "http://www.ncbi.nlm.nih.gov/pubmed/24642292", "http://www.ncbi.nlm.nih.gov/pubmed/8920722", "http://www.ncbi.nlm.nih.gov/pubmed/9639687", "http://www.ncbi.nlm.nih.gov/pubmed/10886022", "http://www.ncbi.nlm.nih.gov/pubmed/12736429", "http://www.ncbi.nlm.nih.gov/pubmed/16621680", "http://www.ncbi.nlm.nih.gov/pubmed/16751800", "http://www.ncbi.nlm.nih.gov/pubmed/19563911", "http://www.ncbi.nlm.nih.gov/pubmed/15450422", "http://www.ncbi.nlm.nih.gov/pubmed/18083062", "http://www.ncbi.nlm.nih.gov/pubmed/11357715", "http://www.ncbi.nlm.nih.gov/pubmed/21237724", "http://www.ncbi.nlm.nih.gov/pubmed/12116376", "http://www.ncbi.nlm.nih.gov/pubmed/8676929", "http://www.ncbi.nlm.nih.gov/pubmed/10432996", "http://www.ncbi.nlm.nih.gov/pubmed/26861493", "http://www.ncbi.nlm.nih.gov/pubmed/15784691", "http://www.ncbi.nlm.nih.gov/pubmed/19712750", "http://www.ncbi.nlm.nih.gov/pubmed/11024477", "http://www.ncbi.nlm.nih.gov/pubmed/18979316", "http://www.ncbi.nlm.nih.gov/pubmed/11287293", "http://www.ncbi.nlm.nih.gov/pubmed/24361396" ], "ideal_answer": [ "Yes. The comet assay is frequently used to measure DNA damage in individual cells.", "Evaluation of primary DNA-damage is one way to identify potential genotoxic agents and for this purpose the Comet assay has, for the last decades, been used to monitor DNA single strand and double strand breaks in individual cells", "The comet assay is frequently used to measure DNA damage in individual cells following exposure to mutagens such as ionizing radiation.", "Yes, a comet assay measures radiation-induced mutations in DNA." ], "exact_answer": "yes", "type": "yesno", "id": "601db7fb1cb411341a00004a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Evaluation of primary DNA-damage is one way to identify potential genotoxic agents and for this purpose the Comet assay has, for the last decades, been used to monitor DNA single strand and double strand breaks in individual cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33198930", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 447, "text": "DNA strand-break frequency was examined by means of the comet assay i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19712750", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 926, "text": ". The comet assay (as this method was subsequently named) was able to measure, for the first time, the fraction of radiobiologically hypoxic cells in mouse and human tumors. It was used to determine that the rate of rejoining of DNA breaks was relatively homogenous within an irradiated population of cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18083062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The comet assay is frequently used to measure DNA damage in individual cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8676929", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1139, "text": "Thus a complete repair of DNA damage induced by gamma-irradiation and measurable by the Comet assay was observed, whereas the yield of somatic mutations increased in relation to the radiation dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287293", "endSection": "abstract" }, { "offsetInBeginSection": 59, "offsetInEndSection": 310, "text": "xanthi) mutagenicity assay is the ability to analyze and compare on the same plants under identical treatment conditions both the induced acute DNA damage in somatic cells as measured by the Comet assay and the yield of induced leaf somatic mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287293", "endSection": "abstract" }, { "offsetInBeginSection": 1977, "offsetInEndSection": 2205, "text": "The present study reveals that gamma radiation induces single strand breaks in DNA as measured by alkaline comet assay in bivalves and comet assay serves as a sensitive and rapid method to detect genotoxicity of gamma radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24642292", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 667, "text": "The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24642292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "The single cell gel electrophoresis (SCGE) assay, more commonly known as the comet assay, due to the \"comet-like\" appearance of the cells, was originally developed as a technique to measure the presence of DNA single-strand breaks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22147573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: The neutral comet assay was devised to measure double-stranded DNA breaks, but it has also been used to measure apoptosis based on its characteristic DNA fragmentation patterns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12116376", "endSection": "abstract" }, { "offsetInBeginSection": 1048, "offsetInEndSection": 1170, "text": "2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24642292", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 292, "text": "PURPOSE: The Deoxyribonucleic Acid (DNA) Comet assay, being a quick, simple, sensitive, reliable and fairly inexpensive method for measuring DNA strand breaks, has been used to assess DNA damage caused by gamma radiation in developmental stages of maize weevil Sitophilus zeamais Motschulsky.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18979316", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 520, "text": "This paper attempts a correlation between the induction and repair of DNA damage measured in the comet assay and the clinical observed reaction in order to evaluate the suitability of the comet assay for prediction of radiation sensitivity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10432996", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 528, "text": "gle cell gel electrophoresis (e.g., Comet Assay) and immunofluoresence microscopy to detect the presence of gamma-H2AX foci, we find that Cr[VI] induces DNA double-strand breaks similar to ionizing radiation (IR). We also demo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15450422", "endSection": "abstract" }, { "offsetInBeginSection": 962, "offsetInEndSection": 1159, "text": "ir of DNA damage induced by gamma-irradiation and measurable by the Comet assay was observed, whereas the yield of somatic mutations increased in relation to the radiation dose. Data on the kinetic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287293", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 620, "text": "eased yield of somatic mutations was highly correlated (r = 0.996) with the increased DNA damage measured by the Comet assay immediately after irradiation. With inc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287293", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 696, "text": "rther assess potential co-mutagenic effects of FA, we exposed A549 human lung cells to FA in combination with various mutagens and measured the induction and removal of DNA damage by the comet assay and the production of chromosomal mutations by the cytokinesis-block micronucleus assay (CBMN assay). The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24361396", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 634, "text": "DNA effects were analysed in leukocytes using the alkaline Comet assay, gene mutations and chromosome aberrations were measured in erythrocytes using the flow cytometric Pig-a gene mutation assay and the micronucleus test (applying both microscopic and flow cytometric evaluation), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861493", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 350, "text": "A wide variety of mutagens have been shown to cause DNA alterations detectable with the comet assay, but it is not yet clear whether a relationship exists between the DNA effects and the induction of mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8920722", "endSection": "abstract" }, { "offsetInBeginSection": 754, "offsetInEndSection": 1010, "text": "The transgenerational changes in mutation rates were attributed to the presence of a persistent subset of endogenous DNA lesions (double- and single-strand breaks), measured by the phosphorylated form of histone H2AX (gamma-H2AX) and alkaline Comet assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16751800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "The single-cell electrophoresis (comet) assay is an established method for measuring radiation-induced strand breaks in DNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10665958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The COMET assay is recognized as a rapid and sensitive method in quantifying radiation induced DNA damage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21237724", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The relationship between cellular radiosensitivity and radiation-induced DNA damage measured by the comet assay.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12736429", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Reliable Comet assay measurements for detecting DNA damage induced by ionising radiation and chemicals.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16621680", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Radiation sensitivity of lymphocytes from healthy individuals and cancer patients as measured by the comet assay.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11357715", "endSection": "title" }, { "offsetInBeginSection": 1162, "offsetInEndSection": 1332, "text": "The comet assay is a potential tool for use in neutron therapy, as well as a method for the rapid screening of samples from individuals accidentally exposed to radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11024477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Induction and repair of DNA damage as measured by the Comet assay and the yield of somatic mutations in gamma-irradiated tobacco seedlings.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287293", "endSection": "title" }, { "offsetInBeginSection": 448, "offsetInEndSection": 611, "text": "The increased yield of somatic mutations was highly correlated (r = 0.996) with the increased DNA damage measured by the Comet assay immediately after irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11287293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The alkaline version of single cell gel electrophoresis (comet) assay is widely used for evaluating DNA damage at the individual cell level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19563911", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1061, "text": "Induction (2 and 5 Gy) of gamma-ray-induced DNA damage and its repair (during 60 min after irradiation) was measured with the alkaline and neutral comet assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15784691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be a promising tool for measuring DNA damage at the individual cell level in both in vitro and in vivo studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9639687", "endSection": "abstract" }, { "offsetInBeginSection": 929, "offsetInEndSection": 1339, "text": "Considering our previous studies showing significant increases in the frequency of cytogenetic damage (when measured as micronuclei) in patients treated with relatively low doses of 131I, the results obtained in the present work by using the Comet assay could indicate that 1 week after the exposure most of the radioiodine-induced DNA lesions, that can be detected with this assay, have already been repaired.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9639687", "endSection": "abstract" }, { "offsetInBeginSection": 1283, "offsetInEndSection": 1437, "text": "Hence, we are using the single-cell gel electrophoresis (comet assay) to detect mouse mutants that display a genetic susceptibility to ionizing radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10886022", "endSection": "abstract" }, { "offsetInBeginSection": 1438, "offsetInEndSection": 1644, "text": "We have established the analysis parameters in the comet assay which are currently used to detect radiation-sensitive mouse mutants and to control the variance within the mouse population in the ENU screen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10886022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Comet assay as a tool to screen for mouse models with inherited radiation sensitivity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10886022", "endSection": "title" } ] }, { "body": "What is formative pluripotency?", "_type": "list", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30017589", "http://www.ncbi.nlm.nih.gov/pubmed/28143843", "http://www.ncbi.nlm.nih.gov/pubmed/25349449", "http://www.ncbi.nlm.nih.gov/pubmed/29359419" ], "_body": "Which are the main genes of formative pluripotency?", "ideal_answer": [ "Formative pluripotency features a gene regulatory network switch from the nave state. Two phases of pluripotency, called nave and primed, have previously been described.", "Two phases of pluripotency, called na\u00efve and primed, have previously been described. The transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that is called formative pluripotency.", "Formative pluripotency features a gene regulatory network switch from the na ve state and comprises capacitation of enhancers, signaling pathways and epigenetic machinery in order to install competence for lineage specification.", "Formative pluripotency is an intermediate stage in the developmental continuum. It's a bit of a misnomer. The term \"formative\" comes from the word \"formal\" which is used to refer to an intermediate state that isn't fully formed.", "Formative pluripotency features a gene regulatory network switch from the na\u00efve state and comprises capacitation of enhancers, signaling pathways and epigenetic machinery in order to install competence for lineage specification. Here, we discuss an intermediate stage of pluripotency that we term \"formative\". Notably, these studies show that the transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that we term formative pluripotency. In this Hypothesis article, a third phase, called formative pluripotency, is proposed to exist as part of a developmental continuum between the na\u00efve and primed phases. Two phases of pluripotency, called na\u00efve and primed, have previously been described.", "Formative pluripotency is an intermediate state of differentiation that we call \"formative\". It is proposed to exist as part of a developmental continuum between the na\u00efve and primed phases. It consists of a gene regulatory network switch from the na\u00efve state to the formative epiblast-like cells of EpiLCs." ], "type": "summary", "id": "5fdb2f54a43ad31278000012", "snippets": [ { "offsetInBeginSection": 199, "offsetInEndSection": 415, "text": "Here, we show that the transcription factor GRHL2 is necessary and sufficient to activate an epithelial subset of enhancers as naive embryonic stem cells (ESCs) transition into formative epiblast-like cells (EpiLCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30017589", "endSection": "abstract" }, { "offsetInBeginSection": 711, "offsetInEndSection": 951, "text": "Notably, these studies show that the transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that we term formative pluripotency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25349449", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 811, "text": "Here, we discuss an intermediate stage of pluripotency that we term \"formative\". Formative pluripotency features a gene regulatory network switch from the na\u00efve state and comprises capacitation of enhancers, signaling pathways and epigenetic machinery in order to install competence for lineage specification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29359419", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 670, "text": "Two phases of pluripotency, called na\u00efve and primed, have previously been described. In this Hypothesis article, a third phase, called formative pluripotency, is proposed to exist as part of a developmental continuum between the na\u00efve and primed phases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28143843", "endSection": "abstract" } ] }, { "body": "Has the companion diagnostic HercepTest received FDA approval?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30668632" ], "ideal_answer": [ "Yes, the HercepTest has received FDA approval." ], "exact_answer": "yes", "type": "yesno", "id": "606c017294d57fd879000076", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The FDA-Approved Breast Cancer HER2 Evaluation Kit (HercepTest; Dako) May Miss Some HER2-Positive Breast Cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30668632", "endSection": "title" }, { "offsetInBeginSection": 121, "offsetInEndSection": 415, "text": "HER2 fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests were performed on 52 cases using a US Food and Drug Administration (FDA)-approved kit (HercepTest, FDA kit) and a laboratory-developed test (LDT) with the HercepTest antibody and a Leica Bond automated stainer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30668632", "endSection": "abstract" } ] }, { "body": "Which R/Bioconductor package has been developed for visualizing differential amino acid group usage in proteomics?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33156866" ], "ideal_answer": [ "DagLogo is an R/Bioconductor package for identifying and visualizing differential amino acid group usage in proteomics data. DagLogo allows various formats for input sets and provides comprehensive options to build optimal background models. It implements different reduced AA alphabets to group AAs of similar properties. Furthermore, dagLogo provides statistical and visual solutions for differential AA (or AA group) usage analysis of both large and small data sets. Case studies showed that dagLogo can better identify and visualize conserved protein sequence patterns from different types of inputs and can potentially reveal the biological patterns that could be missed by other logo generators.", "dagLogo is an R/Bioconductor package for identifying and visualizing differential amino acid group usage in data. dagLogo allows various formats for input sets and provides comprehensive options to build optimal background models.", "DagLogo is an R/Bioconductor package for identifying and visualizing differential amino acid group usage in proteomics data." ], "exact_answer": [ "DagLogo" ], "type": "factoid", "id": "601ebba41cb411341a00005a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "dagLogo: An R/Bioconductor package for identifying and visualizing differential amino acid group usage in proteomics data", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33156866", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1402, "text": "Sequence logos have been widely used as graphical representations of conserved nucleic acid and protein motifs. Due to the complexity of the amino acid (AA) alphabet, rich post-translational modification, and diverse subcellular localization of proteins, few versatile tools are available for effective identification and visualization of protein motifs. In addition, various reduced AA alphabets based on physicochemical, structural, or functional properties have been valuable in the study of protein alignment, folding, structure prediction, and evolution. However, there is lack of tools for applying reduced AA alphabets to the identification and visualization of statistically significant motifs. To fill this gap, we developed an R/Bioconductor package dagLogo, which has several advantages over existing tools. First, dagLogo allows various formats for input sets and provides comprehensive options to build optimal background models. It implements different reduced AA alphabets to group AAs of similar properties. Furthermore, dagLogo provides statistical and visual solutions for differential AA (or AA group) usage analysis of both large and small data sets. Case studies showed that dagLogo can better identify and visualize conserved protein sequence patterns from different types of inputs and can potentially reveal the biological patterns that could be missed by other logo generators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33156866", "endSection": "abstract" } ] }, { "body": "Dasatinib and Blinatumomab are used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32170867", "http://www.ncbi.nlm.nih.gov/pubmed/32569380", "http://www.ncbi.nlm.nih.gov/pubmed/33085860", "http://www.ncbi.nlm.nih.gov/pubmed/20038231", "http://www.ncbi.nlm.nih.gov/pubmed/33168588" ], "ideal_answer": [ "Dasatinib and Blinatumomab produces molecular responses in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia." ], "exact_answer": [ "Philadelphia chromosome-positive acute lymphoblastic leukemia" ], "type": "factoid", "id": "601cb2e41cb411341a000023", "snippets": [ { "offsetInBeginSection": 650, "offsetInEndSection": 767, "text": "Tyrosine kinase inhibitors (imatinib or dasatinib) were added in Philadelphia chromosome-positive (Ph-positive) ALL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32170867", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 1180, "text": "Moreover, combined BCL-2 or MCL1 inhibition with dasatinib showed potent killing in primary Ph+ B-ALL cases, but the BH3-mimetic combination appeared superior in vitro in a variety of Ph-like ALL samples. In PDX models, combined BCL-2 and MCL1 targeting eradicated ALL from Ph- and Ph+ B-ALL cases, although fatal tumor lysis was observed in some instances of high tumor burden. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32569380", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "A phase II trial shows that a chemotherapy-free regimen of dasatinib and blinatumomab produces molecular responses in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33168588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085860", "endSection": "title" }, { "offsetInBeginSection": 220, "offsetInEndSection": 457, "text": "METHODS: We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085860", "endSection": "abstract" }, { "offsetInBeginSection": 1575, "offsetInEndSection": 1895, "text": "CONCLUSIONS: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "A phase II trial shows that a chemotherapy-free regimen of dasatinib and blinatumomab produces molecular responses in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33168588", "endSection": "abstract" }, { "offsetInBeginSection": 1581, "offsetInEndSection": 1899, "text": "SIONS: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Fun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085860", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 658, "text": "Dasatinib is a dual BCR-ABL/Src-family kinase (SFK) inhibitor approved for patients with imatinib-resistant and -intolerant CML in any phase and Ph+ ALL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20038231", "endSection": "abstract" } ] }, { "body": "Is phosphoenolpyruvate carboxykinase 1 (PCK1) the rate-limiting enzyme in gluconeogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31883179", "http://www.ncbi.nlm.nih.gov/pubmed/31911238", "http://www.ncbi.nlm.nih.gov/pubmed/32004540", "http://www.ncbi.nlm.nih.gov/pubmed/32001301", "http://www.ncbi.nlm.nih.gov/pubmed/32058049" ], "ideal_answer": [ "Yes, Pck1 is a rate-limiting gluconeogenic enzyme, where its deficiency or mutation contributes to serious clinical situations as neonatal hypoglycemia and liver failure." ], "exact_answer": "yes", "type": "yesno", "id": "6033f5541cb411341a00014c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 107, "text": "Phosphoenolpyruvate carboxykinase (PEPCK) is a metabolic enzyme in the gluconeogenesis pathway,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31911238", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1112, "text": "PEPCK, a key enzyme involved in gluconeogenesis associated with a decrease in the expression of master genes involved in the VLDL synthesis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32001301", "endSection": "abstract" }, { "offsetInBeginSection": 590, "offsetInEndSection": 905, "text": "Transcriptome analysis of rate-limiting enzymes involved in hepatic gluconeogenesis revealed that moxifloxacin and gatifloxacin at a concentration of 1000\u00a0\u03bcM did not affect the expression of key gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase, glucose 6-phosphatase, and fructose 1,6-bisphosphatase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32004540", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 280, "text": "Pck1 is a rate-limiting gluconeogenic enzyme, where its deficiency or mutation contributes to serious clinical situations as neonatal hypoglycemia and liver failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31883179", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 572, "text": "the gluconeogenesis key enzymes PEPCK (phosphoenolpyruvate carboxykinase) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32058049", "endSection": "abstract" } ] }, { "body": "What conditions are diagnosed using the scratch collapse test?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21681130", "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "http://www.ncbi.nlm.nih.gov/pubmed/32474897", "http://www.ncbi.nlm.nih.gov/pubmed/28284457", "http://www.ncbi.nlm.nih.gov/pubmed/24876682", "http://www.ncbi.nlm.nih.gov/pubmed/30349795", "http://www.ncbi.nlm.nih.gov/pubmed/28828917", "http://www.ncbi.nlm.nih.gov/pubmed/32698624", "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "http://www.ncbi.nlm.nih.gov/pubmed/27625547", "http://www.ncbi.nlm.nih.gov/pubmed/26330768", "http://www.ncbi.nlm.nih.gov/pubmed/33054988", "http://www.ncbi.nlm.nih.gov/pubmed/19774420", "http://www.ncbi.nlm.nih.gov/pubmed/23855039", "http://www.ncbi.nlm.nih.gov/pubmed/29036022" ], "ideal_answer": [ "Scouring collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome.", "The scratch collapse test (SCT) is a clinical examination maneuver that has been reported as a reliable and reproducible test to diagnose carpal tunnel syndrome (CTS) cubital tunnel syndrome and other compressive upper limb neuropathies.", "Scales collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome.", "Scratch collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome.", "Evaluation of the Scratch Collapse Test for Carpal and Cubital Tunnel Syndrome-A Prospective, Blinded Study.", "Scrap collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome.", " A diagnostic maneuver known as the \"scratch-collapse test\" (SCT), to aid in the diagnosis of compressive upper limb neuropathies such as carpal tunnel syndrome (CTS)," ], "exact_answer": [ [ "carpal tunnel syndrome", "compressive neuropathy", "entrapment neuropathy" ], [ "cubital tunnel syndrome", "Compressive neuropathy of the ulnar nerve across the elbow" ] ], "type": "list", "id": "601eac531cb411341a000054", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Evaluation of the scratch collapse test for the diagnosis of carpal tunnel syndrome", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23855039", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "This prospective study measured and compared the diagnostic performance characteristics of various clinical signs and physical examination manoeuvres for carpal tunnel syndrome (CTS), including the scratch collapse test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23855039", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 176, "text": " A diagnostic maneuver known as the \"scratch-collapse test\" (SCT), to aid in the diagnosis of compressive upper limb neuropathies such as carpal tunnel syndrome (CTS), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28284457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Accuracy of the Scratch Collapse Test for Carpal Tunnel Syndrome in Comparison With Electrodiagnostic Studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32698624", "endSection": "title" }, { "offsetInBeginSection": 1176, "offsetInEndSection": 1554, "text": "Conclusion: Based on this study and previous findings by other authors, we would advise against the use of the SCT in CTS for important patient-care decisions, such as surgical decision-making, until future research is done. It is possible that the SCT, in combination with other physical examination maneuvers, could increase diagnostic accuracy and enhance patient management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32698624", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 845, "text": "Compressive neuropathy of the ulnar nerve across the elbow is a common diagnosis encountered frequently within a hand and upper extremity clinical practice. Appropriate and timely evaluation, diagnosis, objective testing, and evidence-based decisions regarding treatment options are paramount in the optimal care of the patient with this pathology. An understanding of current literature is critical in determining and understanding best practices.RECENT FINDINGS: A thorough review of the recent literature regarding physical examination, diagnostic testing, and nonoperative versus operative results was performed. Regarding physical examination, the glenohumeral internal rotation test and scratch collapse test are more effective and sensitive than traditional maneuvers such as Tinel's testing and the elbow flexion test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32474897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Evaluation of the Scratch Collapse Test for Carpal and Cubital Tunnel Syndrome-A Prospective, Blinded Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 223, "text": " clarify the sensitivity, specificity, and interrater reliability of the scratch collapse test for carpal tunnel syndrome (CTS) and cubital tunnel syndrome, using blinded observers in a general patient population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 189, "text": "The scratch collapse test (SCT) is a clinical examination maneuver that has been previously reported as a reliable and reproducible test to diagnose carpal tunnel syndrome (CTS)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32698624", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1723, "text": "SIONS: The scratch collapse test had significantly higher sensitivity than Tinel's test and the flexion/nerve compression test for carpal tunnel and cubital tunnel syndromes. Accur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "PURPOSE: The purpose of this study was to evaluate the clinical usefulness of a new test, the scratch collapse test, for the diagnosis of carpal tunnel syndrome and cubital tunnel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1341, "text": "This study suggests that the scratch collapse test may be a reliable physical examination technique for localizing the point of maximal nerve compression in patients with cubital tunnel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19774420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The objective of this study is to demonstrate the utility of the scratch collapse test (SCT) in localizing the point of maximal compression in cubital tunnel syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19774420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "PURPOSE: To clarify the sensitivity, specificity, and interrater reliability of the scratch collapse test for carpal tunnel syndrome (CTS) and cubital tunnel syndrome, using blinded observers in a general patient population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Evaluation of the scratch collapse test for the diagnosis of carpal tunnel syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23855039", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Scratch collapse test for evaluation of carpal and cubital tunnel syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "title" }, { "offsetInBeginSection": 1275, "offsetInEndSection": 1376, "text": "scratch collapse test had the highest negative predictive value (73%) for carpal tunnel syndrome. Tin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "The utility of the scratch collapse test has been demonstrated in examination of patients with carpal and cubital tunnel syndromes and long thoracic and peroneal nerve compressions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29036022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The scratch collapse test (SCT) is a relatively new clinical test in which a positive result implies entrapment neuropathy of the nerve tested. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27625547", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "PURPOSE: The purpose of this study was to evaluate the clinical usefulness of a new test, the scratch collapse test, for the diagnosis of carpal tunnel syndrome and cubital tunnel s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Background: The scratch collapse test (SCT) is a clinical examination maneuver that has been previously reported as a reliable and reproducible test to diagnose carpal tunnel synd", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32698624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "The scratch collapse test in the diagnosis of compression of the median nerve in the proximal forearm", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28828917", "endSection": "title" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1357, "text": "ts that the scratch collapse test may be a reliable physical examination technique for localizing the point of maximal nerve compression in patients with cubital tunnel syndrome. That point, in ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19774420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The utility of the scratch collapse test has been demonstrated in examination of patients with carpal and cubital tunnel syndromes and long thoracic and peroneal nerve compressions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29036022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "PURPOSE: A diagnostic maneuver known as the \"scratch-collapse test\" (SCT), to aid in the diagnosis of compressive upper limb neuropathies such as carpal tunnel syndrome (CTS), has been descri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28284457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Scratch Collapse Test Localizes Osborne's Band as the Point of Maximal Nerve Compression in Cubital Tunnel Syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19774420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The reliability of the scratch-collapse test for diagnosis of carpal tunnel syndrome (CTS) has not been tested by independent investigators. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24876682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "The scratch collapse test in the diagnosis of compression of the median nerve in the proximal forearm.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28828917", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Scratch Collapse Test Is a Useful Clinical Sign in Assessing Long Thoracic Nerve Entrapment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27625547", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Scratch Collapse Test for Carpal Tunnel Syndrome: A Systematic Review and Meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30349795", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The scratch collapse test (SCT) is a relatively new clinical test in which a positive result implies entrapment neuropathy of the nerve tested.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27625547", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 361, "text": "The 'Scratch Collapse Test' (SCT) has emerged as a new provocative test to assist in the localisation of peripheral nerve compression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33054988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "PURPOSE: A diagnostic maneuver known as the \"scratch-collapse test\" (SCT), to aid in the diagnosis of compressive upper limb neuropathies such as carpal tunnel syndrome (CTS), has been described", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28284457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "The \"hierarchical\" Scratch Collapse Test for identifying multilevel ulnar nerve compression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26330768", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Our purpose was to review the clinical usefulness of the scratch collapse test (SCT) in the diagnosis of proximal entrapment of the median nerve in the forearm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28828917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "PURPOSE: To clarify the sensitivity, specificity, and interrater reliability of the scratch collapse test for carpal tunnel syndrome (CTS) and cubital tunnel syndrome, using blinded observers in a general patient population", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "endSection": "abstract" }, { "offsetInBeginSection": 1381, "offsetInEndSection": 1603, "text": "SIONS: The sensitivity of the scratch collapse test for CTS and cubital tunnel syndrome was lower than that found in other studies, regardless of whether a clinical or an electrodiagnostic reference standard was used. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "endSection": "abstract" }, { "offsetInBeginSection": 1695, "offsetInEndSection": 1836, "text": " results call into question the sensitivity and interrater reliability of the scratch collapse test for CTS and cubital tunnel syndrome.TYPE ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Evaluation of the scratch collapse test in peroneal nerve compression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21681130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND: The scratch collapse test is a recently described provocative test for diagnosis of peripheral nerve compression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21681130", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1113, "text": "r carpal tunnel syndrome, sensitivities were 64%, 32%, and 44% for the scratch collapse test, Tinel's test, and wrist flexion/compression test, respectively. F", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 1273, "offsetInEndSection": 1374, "text": "e scratch collapse test had the highest negative predictive value (73%) for carpal tunnel syndrome. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1272, "text": "r cubital tunnel syndrome, sensitivities were 69%, 54%, and 46% for the scratch collapse test, Tinel test, and elbow flexion/compression test, respectively. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 190, "text": "The purpose of this study was to evaluate the clinical usefulness of a new test, the scratch collapse test, for the diagnosis of carpal tunnel syndrome and cubital tunnel syndrome.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "BACKGROUND: The scratch collapse test is a recently described provocative test for diagnosis of peripheral nerve compression.METHODS: The scratch collapse test was studied prospectively in 24 consecutive patients with a diagnosis of common peroneal nerve co", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21681130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "PURPOSE: The purpose of this study was to evaluate the clinical usefulness of a new test, the scratch collapse test, for the diagnosis of carpal tunnel syndrome and cubital tunnel syndrome.METHODS: The scratch collapse test was prospectively compared with Tinel's sign and flexion/nerve compression in 169 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18984333", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 400, "text": "PURPOSE: To clarify the sensitivity, specificity, and interrater reliability of the scratch collapse test for carpal tunnel syndrome (CTS) and cubital tunnel syndrome, using blinded observers in a general patient population.METHODS: Ninety-two subjects were recruited from all patients referred for electrodiagnostic studies for upper extremity symptoms that were thought to be related to an entrapme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32299690", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 764, "text": "odiagnostic testing. Provocative testing by the scratch collapse test and Tinel's sign was performed.RESULTS: The scratch collapse test showed a sensitivity of 0.77 and a specificity of 0.99, while the Tinel's sign showed 0.65 and 0.99, respectively.CONCLUSION: The scratch collapse test is a sensitive and specific provocative test that compares favorably to existing clinical tests and aids in the diagnosis of ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21681130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The reliability of the scratch-collapse test for diagnosis of carpal tunnel syndrome (CTS) has not been tested by independent investigators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24876682", "endSection": "abstract" } ] }, { "body": "Which is the main gene signature in Systemic Lupus Erythematosus (SLE)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23400715", "http://www.ncbi.nlm.nih.gov/pubmed/15593221", "http://www.ncbi.nlm.nih.gov/pubmed/18075793", "http://www.ncbi.nlm.nih.gov/pubmed/27009916", "http://www.ncbi.nlm.nih.gov/pubmed/19790071", "http://www.ncbi.nlm.nih.gov/pubmed/30745462", "http://www.ncbi.nlm.nih.gov/pubmed/31130331", "http://www.ncbi.nlm.nih.gov/pubmed/25861459", "http://www.ncbi.nlm.nih.gov/pubmed/31044165", "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "http://www.ncbi.nlm.nih.gov/pubmed/32334613", "http://www.ncbi.nlm.nih.gov/pubmed/17849124", "http://www.ncbi.nlm.nih.gov/pubmed/20538795", "http://www.ncbi.nlm.nih.gov/pubmed/24598455", "http://www.ncbi.nlm.nih.gov/pubmed/31660791", "http://www.ncbi.nlm.nih.gov/pubmed/24379124", "http://www.ncbi.nlm.nih.gov/pubmed/19479852", "http://www.ncbi.nlm.nih.gov/pubmed/15511676", "http://www.ncbi.nlm.nih.gov/pubmed/23754736", "http://www.ncbi.nlm.nih.gov/pubmed/29644082", "http://www.ncbi.nlm.nih.gov/pubmed/23028528", "http://www.ncbi.nlm.nih.gov/pubmed/24839407", "http://www.ncbi.nlm.nih.gov/pubmed/12642603", "http://www.ncbi.nlm.nih.gov/pubmed/24834763", "http://www.ncbi.nlm.nih.gov/pubmed/31890206", "http://www.ncbi.nlm.nih.gov/pubmed/23083033", "http://www.ncbi.nlm.nih.gov/pubmed/30185417", "http://www.ncbi.nlm.nih.gov/pubmed/27723281", "http://www.ncbi.nlm.nih.gov/pubmed/27094810", "http://www.ncbi.nlm.nih.gov/pubmed/21803750", "http://www.ncbi.nlm.nih.gov/pubmed/19968664", "http://www.ncbi.nlm.nih.gov/pubmed/22242767" ], "ideal_answer": [ "Systemic Lupus Erythematosus (SLE) has a type I interferon (IFN) gene signature.", "SLE is characterized by a type-I interferon gene signature.", "Systemic Lupus Erythematosus (SLE) is a type I interferon (IFN) disease. The main gene signature is a 4-gene expression of 4 genes.", "SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE.", "A role for interferon (IFN) in systemic lupus erythematosus (SLE) pathogenesis is inferred from the prominent IFN gene signature (IGS), but the major IFN species and its relationship to disease activity are unknown." ], "exact_answer": [ "IFN signature", "Interferon signature" ], "type": "factoid", "id": "5fdb42e7a43ad31278000026", "snippets": [ { "offsetInBeginSection": 393, "offsetInEndSection": 653, "text": "The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element-luciferase reporter cell assays and type I IFN gene signature induction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29644082", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 640, "text": "Randomization was stratified by SLE Disease Activity Index 2000 score (<10 or \u226510), oral corticosteroid dosage (<10 or \u226510 mg/day), and type I IFN gene signature test status (high or low) based on a 4-gene expression assay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" }, { "offsetInBeginSection": 1703, "offsetInEndSection": 1750, "text": "patients with a high IFN signature at baseline ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130918", "endSection": "abstract" }, { "offsetInBeginSection": 389, "offsetInEndSection": 543, "text": "Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27009916", "endSection": "abstract" }, { "offsetInBeginSection": 278, "offsetInEndSection": 543, "text": "Our group, using microarray analysis, identified the interferon (IFN) gene signature in pediatric systemic lupus erythematosus (SLE) and has published data that suggest high doses of intravenous corticosteroid treatment may have benefit over strictly oral regimens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24839407", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 406, "text": "In this study, we report the presence of IFN activation in SLE bone marrow (BM), as measured by an IFN gene signature, increased IFN regulated chemokines, and direct production of IFN by BM-resident cells, associated with profound changes in B cell development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379124", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 853, "text": "Pronounced alterations in B cell development were noted in SLE in the presence of an IFN signature with a reduction in the fraction of pro/pre-B cells, suggesting an inhibition in early B cell development and an expansion of B cells at the transitional stage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379124", "endSection": "abstract" }, { "offsetInBeginSection": 815, "offsetInEndSection": 992, "text": " At baseline, patients had moderate-to-severe disease activity (mean SLE Disease Activity Index score 11.0), and most (75.2%) had a high type I interferon (IFN) gene signature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400715", "endSection": "abstract" }, { "offsetInBeginSection": 1383, "offsetInEndSection": 1502, "text": "Inhibition of the type I IFN gene signature was sustained during treatment in patients with a high baseline signature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400715", "endSection": "abstract" }, { "offsetInBeginSection": 2209, "offsetInEndSection": 2469, "text": "Patient baseline body WT, interferon gene signature from 21 genes, steroid use, and sifalimumab dose were identified as significant covariates for CL, whereas only baseline body WT was a significant covariate for V 1 and peripheral volume of distribution (V 2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754736", "endSection": "abstract" }, { "offsetInBeginSection": 872, "offsetInEndSection": 1170, "text": "These include: type I interferon (IFN) gene signature as a pharmacodynamic marker and potential predictive marker for anti-type I IFN therapy; anti-double stranded DNA as a disease marker and potential predictive marker for flares; the complements and neutrophil signatures as disease marker of SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083033", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1363, "text": "All SLE B cell populations revealed an interferon (IFN) gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23028528", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 907, "text": "A five gene type I IFN signature was assessed in these subjects to identify subpopulations showing both activation and concordance of the type I IFN pathway in the peripheral blood and disease-affected tissues of each disease and to correlate activation of this pathway in the WB with clinical measurements", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803750", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1350, "text": "aseline disease activity measurements correlated with a type I IFN gene signature in the WB of subjects with SLE, PM and SSc, as did various serum autoantibody levels in subjects with SLE and DM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21803750", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 709, "text": "Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (P < .0001) were found to be up-regulated in platelets from SLE patients compared with healthy volunteers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538795", "endSection": "abstract" }, { "offsetInBeginSection": 1156, "offsetInEndSection": 1257, "text": "In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538795", "endSection": "abstract" }, { "offsetInBeginSection": 274, "offsetInEndSection": 723, "text": "During the trial, we also examined whether overexpression of an IFNalpha/beta-inducible gene signature in whole blood could serve as a pharmacodynamic biomarker to evaluate IFNalpha neutralization and investigated downstream effects of neutralizing IFNalpha on BAFF and other key signaling pathways, i.e., granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), tumor necrosis factor alpha (TNFalpha), and IL-1beta, in SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19479852", "endSection": "abstract" }, { "offsetInBeginSection": 1566, "offsetInEndSection": 1706, "text": "IFNalpha/beta-inducible gene signatures in whole blood are effective pharmacodynamic biomarkers to evaluate anti-IFNalpha mAb therapy in SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19479852", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 261, "text": "SLE is characterized by a type-I interferon gene signature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17849124", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1201, "text": "These observations provide a link between dysregulation of apoptosis and phagocytosis and the type-I interferon signature observed in SLE patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17849124", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 474, "text": "Of interest, the IFN gene 'signature' correlates with more severe disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15511676", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "A role for interferon (IFN) in systemic lupus erythematosus (SLE) pathogenesis is inferred from the prominent IFN gene signature (IGS), but the major IFN species and its relationship to disease activity are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31044165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Interferon (IFN) signature genes have been shown to be expressed highly in peripheral blood of patients with systemic lupus erythematosus (SLE), especially in the presence of active disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19968664", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "OBJECTIVE: The interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30185417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "BACKGROUND: There is increased expression of type I interferon (IFN)-regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22242767", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "OBJECTIVES: The interferon (IFN) signature (IS) in patients with systemic lupus erythematosus (SLE) includes over 100 genes induced by type I IFN pathway acti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25861459", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "A role for interferon (IFN) in systemic lupus erythematosus (SLE) pathogenesis is inferred from the prominent IFN gene signature (IGS), but the major IFN species and its relationship to disease activity are unknown. A bi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31044165", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 551, "text": " group, using microarray analysis, identified the interferon (IFN) gene signature in pediatric systemic lupus erythematosus (SLE) and has published data that suggest high doses of intravenous corticosteroid treatment may have benefit over strictly oral regimens. Additio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24839407", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "INTRODUCTION: A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Patients with systemic lupus erythematosus (SLE) have an increased expression of type I interferon (IFN)-regulated genes (an IFN signature), which is caused by an ongoing production of type I IFNs by plasmacytoid dendritic cells (pDCs). The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27094810", "endSection": "abstract" }, { "offsetInBeginSection": 271, "offsetInEndSection": 376, "text": " This study investigated serum IL-3 and IFN levels, and a whole blood 'IL-3 gene signature', in human SLE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31890206", "endSection": "abstract" }, { "offsetInBeginSection": 1453, "offsetInEndSection": 1652, "text": "SION: SLE patients demonstrated increased expression of an IFN response gene signature (75% of patients had an elevated IFN response gene signature) at baseline in ILLUMINATE-1 and ILLUMINATE-2. Subs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27723281", "endSection": "abstract" }, { "offsetInBeginSection": 1417, "offsetInEndSection": 1572, "text": "SLE patients exhibit increased IFN signatures in their skin secondary to increased production and a robust, skewed IFN response that is regulated by PITX1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30745462", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 347, "text": " An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN-regulated chemokines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19790071", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 380, "text": " The role of type I interferon (IFN) in SLE has been demonstrated from the 2000s, by gene expression analyses showing significant over-expression of genes related to type I IFN signalling pathway (IFN signature)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32334613", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 193, "text": "The type I interferon (IFN) gene signature and circulating autoantibodies are hallmarks of SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31130331", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 387, "text": "Many SLE patients have increased serum levels of IFN-alpha and display an IFN gene expression \"signature\" characterized by strong overexpression of IFN-responsive genes in leukocytes and target tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18075793", "endSection": "abstract" }, { "offsetInBeginSection": 381, "offsetInEndSection": 504, "text": " However, several studies questioned the role of measuring the intensity of IFN signature (IFN score) to chase SLE activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32334613", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 439, "text": "A bioinformatic approach employing individual IFN species gene signatures to interrogate SLE microarray datasets demonstrates a putative role for numerous IFN species, with prominent expression of IFNB1 and IFNW signatures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31044165", "endSection": "abstract" }, { "offsetInBeginSection": 1566, "offsetInEndSection": 1733, "text": "GS test-high patients overexpressed many gene signatures associated with SLE pathogenesis compared with IFNGS test-low patients, reflecting broad immune activation. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31660791", "endSection": "abstract" }, { "offsetInBeginSection": 1189, "offsetInEndSection": 1257, "text": "I IFN signature could be a novel marker for vascular disease in SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538795", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 708, "text": "Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (P < .0001) were found to be up-regulated in platelets from SLE patients compared with healthy volunteers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20538795", "endSection": "abstract" }, { "offsetInBeginSection": 417, "offsetInEndSection": 533, "text": "An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24834763", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 338, "text": "Using oligonucleotide microarrays, we now show that active SLE can be distinguished by a remarkably homogeneous gene expression pattern with overexpression of granulopoiesis-related and interferon (IFN)-induced genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12642603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 447, "text": "OBJECTIVE: To study the contribution of interferon-alpha (IFNalpha) and IFNgamma to the IFN gene expression signature that has been observed in microarray screens of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).METHODS: Quantitative real-time polymerase chain reaction analysis of healthy control PBMCs was used to determine the relative induction of a panel of IFN-inducible genes (IFIGs) by IF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15593221", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 651, "text": "osus (SLE). Patients with SLE have increased IFN-regulated gene expression pointing towards a possible underlying genetic defect.OBJECTIVES: To determine expression levels of five type I IFN-regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity.METHODS: Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, incl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22242767", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1124, "text": "Up-regulation of a set of 63 IFN signature genes was seen in 83% of SLE patients and 50% of ILE patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19968664", "endSection": "abstract" } ] }, { "body": "Has FTY720 been considered for the treatment of stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31785606" ], "ideal_answer": [ "Yes, FTY720 is a strong candidate for stroke treatment." ], "exact_answer": "yes", "type": "yesno", "id": "605265ee94d57fd87900000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "FTY720 (Fingolimod) Ameliorates Brain Injury through Multiple Mechanisms and is a Strong Candidate for Stroke Treatment", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31785606", "endSection": "title" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1691, "text": "Many researchers have recognized the positive effects of FTY720 and launched basic and clinical experiments to test the use of this agent against stroke. Although the mechanism of FTY720 has not been fully elucidated, its efficacy against cerebral stroke is becoming clear, not only in animal models, but also in ischemic stroke patients through clinical trials. In this article, we review the data obtained from laboratory findings and preliminary clinical trials using FTY720 for stroke treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31785606", "endSection": "abstract" } ] }, { "body": "List R packages for lipidomics", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30977807", "http://www.ncbi.nlm.nih.gov/pubmed/30500173", "http://www.ncbi.nlm.nih.gov/pubmed/28989334", "http://www.ncbi.nlm.nih.gov/pubmed/32168452" ], "ideal_answer": [ "R packages for lipidomics: lipidomics, masspix, lipidms, lipidr and lipid mini-on.", "R packages for lipidomics include: lipidr, masspix, lipidms, lipidr and lipid mini-on.", "Lipidomics, masspix, lipidms, lipidr and lipid mini-on are R packages for lipidomics.", "Lipid Mini-On, lipidr, LipidMS and massPix" ], "exact_answer": [ [ "massPix" ], [ "LipidMS" ], [ "lipidr" ], [ "Lipid Mini-On" ] ], "type": "list", "id": "6060838e94d57fd879000042", "snippets": [ { "offsetInBeginSection": 161, "offsetInEndSection": 265, "text": "We have developed massPix-an R package for analysing and interpreting data from MSI of lipids in tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28989334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Lipid Mini-On: mining and ontology tool for enrichment analysis of lipidomic data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30977807", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 513, "text": "Here we introduce Lipid Mini-On, an open-source tool that performs lipid enrichment analyses and visualizations of lipidomics data. Lipid Mini-On uses a text-mining process to bin individual lipid names into multiple lipid ontology groups based on the classification (e.g. LipidMaps) and other characteristics, such as chain length. Lipid Mini-On provides users with the capability to conduct enrichment analysis of the lipid ontology terms using a Shiny app with options of five statistical approaches. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30977807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "lipidr: A Software Tool for Data Mining and Analysis of Lipidomics Datasets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32168452", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1524, "text": "The rapid evolution of mass spectrometry (MS)-based lipidomics has enabled the simultaneous measurement of numerous lipid classes. With lipidomics datasets becoming increasingly available, lipidomic-focused software tools are required to facilitate data analysis as well as mining of public datasets, integrating lipidomics-unique molecular information such as lipid class, chain length, and unsaturation. To address this need, we developed lipidr, an open-source R/Bioconductor package for data mining and analysis of lipidomics datasets. lipidr implements a comprehensive lipidomic-focused analysis workflow for targeted and untargeted lipidomics. lipidr imports numerical matrices, Skyline exports, and Metabolomics Workbench files directly into R, automatically inferring lipid class and chain information from lipid names. Through integration with the Metabolomics Workbench API, users can search, download, and reanalyze public lipidomics datasets seamlessly. lipidr allows thorough data inspection, normalization, and uni- and multivariate analyses, displaying results as interactive visualizations. To enable interpretation of lipid class, chain length, and total unsaturation data, we also developed and implemented a novel lipid set enrichment analysis. A companion online guide with two live example datasets is presented at https://www.lipidr.org/. We expect that the ease of use and innovative features of lipidr will allow the lipidomics research community to gain novel detailed insights from lipidomics data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32168452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "LipidMS: An R Package for Lipid Annotation in Untargeted Liquid Chromatography-Data Independent Acquisition-Mass Spectrometry Lipidomics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30500173", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 480, "text": "High resolution LC-MS untargeted lipidomics using data independent acquisition (DIA) has the potential to increase lipidome coverage, as it enables the continuous and unbiased acquisition of all eluting ions. However, the loss of the link between the precursor and the product ions combined with the high dimensionality of DIA data sets hinder accurate feature annotation. Here, we present LipidMS, an R package aimed to confidently identify lipid species in untargeted LC-DIA-MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30500173", "endSection": "abstract" } ] }, { "body": "Which disease can be treated with Relugolix.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32674208", "http://www.ncbi.nlm.nih.gov/pubmed/32674616", "http://www.ncbi.nlm.nih.gov/pubmed/30741797", "http://www.ncbi.nlm.nih.gov/pubmed/30937733", "http://www.ncbi.nlm.nih.gov/pubmed/32469183", "http://www.ncbi.nlm.nih.gov/pubmed/32911575", "http://www.ncbi.nlm.nih.gov/pubmed/32273183", "http://www.ncbi.nlm.nih.gov/pubmed/32912633", "http://www.ncbi.nlm.nih.gov/pubmed/31461087", "http://www.ncbi.nlm.nih.gov/pubmed/31594635" ], "ideal_answer": [ "Relugolix has a role in treatment of prostate cancer, uterine fibroids, endometriosis and uterine myomas." ], "exact_answer": [ [ "prostate cancer" ], [ "uterine fibroids" ], [ "endometriosis" ], [ "uterine myomas" ] ], "type": "list", "id": "602496791cb411341a00009d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31594635", "endSection": "title" }, { "offsetInBeginSection": 1697, "offsetInEndSection": 1786, "text": "CONCLUSION(S): Relugolix improved uterine fibroid-associated pain and was well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31594635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469183", "endSection": "title" }, { "offsetInBeginSection": 2023, "offsetInEndSection": 2271, "text": "CONCLUSIONS: In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "The Oral Gonadotropin-releasing Hormone Receptor Antagonist Relugolix as Neoadjuvant/Adjuvant Androgen Deprivation Therapy to External Beam Radiotherapy in Patients with Localised Intermediate-risk Prostate Cancer: A Randomised, Open-label, Parallel-group Phase 2 Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32273183", "endSection": "title" }, { "offsetInBeginSection": 2227, "offsetInEndSection": 2526, "text": "CONCLUSIONS: Relugolix achieved testosterone suppression to castrate levels within days and maintained it over 24 wk with a safety profile consistent with its mechanism of action.PATIENT SUMMARY: Oral once-daily relugolix may be a novel oral alternative to injectable androgen deprivation therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32273183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Phase 3 HERO Trial Finds Relugolix to Be Superior to Leuprolide in Prostate Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32674208", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 442, "text": "Results from the phase 3 HERO trial(NCT03085095), presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program, indicated that relugolix (Relumina) demonstrated superiority over leuprolide (Lupron) in sustained testosterone suppression through 48 weeks, fast testosterone recovery after discontinuation, and a 50% reduction in major adverse cardiovascular events (MACE) in patients with advanced prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32674208", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Relugolix for the treatment of uterine fibroids.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32674616", "endSection": "title" }, { "offsetInBeginSection": 430, "offsetInEndSection": 581, "text": "AREAS COVERED: The authors review the current options available for the treatment of women with UF, with a special focus on the newest one, relugolix. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32674616", "endSection": "abstract" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1101, "text": "EXPERT OPINION: Relugolix is a promising drug for the non-surgical treatment of women with UF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32674616", "endSection": "abstract" }, { "offsetInBeginSection": 1404, "offsetInEndSection": 1639, "text": "CONCLUSION(S): Oral administration of relugolix alleviated endometriosis-associated pain in a dose-response manner and was generally well tolerated. Relugolix 40 mg demonstrated efficacy and safety comparable with those of leuprorelin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32912633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32912633", "endSection": "title" }, { "offsetInBeginSection": 2313, "offsetInEndSection": 2650, "text": "CONCLUSION: In women with uterine leiomyomas, once-daily treatment with relugolix, an oral gonadotropin-releasing hormone antagonist, demonstrated noninferiority to monthly leuprorelin for improvement of heavy menstrual bleeding at 6-12 weeks of treatment, had a more rapid effect on menstrual bleeding, and was generally well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30741797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 475, "text": "The orally active nonpeptide gonadotropin-releasing hormone (GnRH)-receptor antagonist relugolix (Relumina) is being developed by Takeda and ASKA Pharmaceutical as a treatment for various sex hormone related disorders. Relugolix was recently approved for marketing in Japan as a treatment for symptoms associated with uterine fibroids, and studies evaluating the efficacy of the drug as treatment for endometriosis-associated pain and prostate cancer are currently underway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30937733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Relugolix for the treatment of uterine fibroids.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31461087", "endSection": "title" }, { "offsetInBeginSection": 673, "offsetInEndSection": 822, "text": "Relugolix is an orally active nonpeptide GnRH-ant, recently licensed for marketing in Japan for the treatment of symptoms related to uterine myomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31461087", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 821, "text": "Relugolix is an orally active nonpeptide GnRH-ant, recently licensed for marketing in Japan for the treatment of symptoms related to uterine myomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31461087", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 474, "text": "Relugolix was recently approved for marketing in Japan as a treatment for symptoms associated with uterine fibroids, and studies evaluating the efficacy of the drug as treatment for endometriosis-associated pain and prostate cancer are currently underway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30937733", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 640, "text": "This article summarizes the milestones in the development of relugolix leading to this first approval for the treatment of symptoms associated with uterine fibroids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30937733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "We here describe a case of the prolapse of pedunculated submucosal leiomyoma through the cervix during the treatment of a gonadotropin-releasing hormone (GnRH) antagonist relugolix.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32911575", "endSection": "abstract" } ] }, { "body": "What is the effect of Carbendazim on bees?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33084067", "http://www.ncbi.nlm.nih.gov/pubmed/33246707" ], "ideal_answer": [ "Carbendazim is an environmental risk factor that likely weakens bee colonies, partially due to reduced expression of major royal jelly proteins, which may be potential causes of colony collapse disorder." ], "type": "summary", "id": "6056fd8a94d57fd87900001e", "snippets": [ { "offsetInBeginSection": 1272, "offsetInEndSection": 1512, "text": "Together, these results suggest that carbendazim is an environmental risk factor that likely weakens bee colonies, partially due to reduced expression of major royal jelly proteins, which may be potential causes of colony collapse disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33246707", "endSection": "abstract" } ] }, { "body": "What 3 organs are the sphincter of Oddi associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7991969", "http://www.ncbi.nlm.nih.gov/pubmed/3058076", "http://www.ncbi.nlm.nih.gov/pubmed/15836453", "http://www.ncbi.nlm.nih.gov/pubmed/11900681", "http://www.ncbi.nlm.nih.gov/pubmed/15143221", "http://www.ncbi.nlm.nih.gov/pubmed/6065875", "http://www.ncbi.nlm.nih.gov/pubmed/3653618", "http://www.ncbi.nlm.nih.gov/pubmed/8419235", "http://www.ncbi.nlm.nih.gov/pubmed/10409171", "http://www.ncbi.nlm.nih.gov/pubmed/31951513", "http://www.ncbi.nlm.nih.gov/pubmed/7549047", "http://www.ncbi.nlm.nih.gov/pubmed/3049055", "http://www.ncbi.nlm.nih.gov/pubmed/2666281", "http://www.ncbi.nlm.nih.gov/pubmed/2052626", "http://www.ncbi.nlm.nih.gov/pubmed/8026537", "http://www.ncbi.nlm.nih.gov/pubmed/19799700" ], "ideal_answer": [ "Sphincter of Oddi is associated with the pancreatic duct, duodenum and gallbladder.", "The sphincter of Oddi is associated with the pancreatic duct, the duodenal crypts and gallbladder.", "Sphincter of Oddi (SO) is a dynamic structure located strategically at the confluence of the bile duct, the pancreatic duct and the duodenum.", "The sphincter of oddsi is associated with the pancreatic duct, the duodenal crypts and the gallbladder.", "The sphincter ofoddi is associated with the pancreatic duct, the duodenal crypts and gallbladder.", "The sphincter of Oddi is a dynamic structure located strategically at the confluence of the bile duct, the pancreatic duct and the duodenum." ], "exact_answer": [ [ "pancreas" ], [ "bile duct" ], [ "duodenum" ] ], "type": "list", "id": "60292e661cb411341a000112", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Sphincter of Oddi (SO) is a dynamic structure located strategically at the confluence of the bile duct, the pancreatic duct and the duodenum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7991969", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 453, "text": "Because the sphincter of Oddi does not regulate the pancreaticobiliary junction in PBM, pancreatic juice frequently refluxes into the biliary tract and can cause various complications, including biliary cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31951513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The most common functional disorders of the biliary tract and pancreas are associated with disordered motility of the sphincter of Oddi (SO). Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15836453", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "We have investigated the existence of neural connections between the duodenum and the sphincter of Oddi (SO). St", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10409171", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 799, "text": "nd set of experiments, sphincter of Oddi was divided into two parts and the effects of field stimulation were studied separately on areas close to the duodenal papilla (area I) and areas close to the common bile duct (area II). In the whole sph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8026537", "endSection": "abstract" }, { "offsetInBeginSection": 918, "offsetInEndSection": 1143, "text": "morphine administered prior to MR cholangiopancreatography can improve image quality by causing the sphincter of Oddi to contract, which increases pressure in and distention of the biliary and pancreatic ducts. Morphine admin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15143221", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 612, "text": "LTS: Two to 3 weeks after gallbladder injection, labeled nerve cell bodies were found in the myenteric plexus of the proximal duodenum but were rare in the duodenum distal to the sphincter of Oddi. No", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8419235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The sphincter of Oddi is the smooth muscle connection between the bile duct and the duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3049055", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 262, "text": "The Sphincter of Oddi is a small smooth muscle sphincter strategically placed at the junction of the bile duct, pancreatic duct, and duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19799700", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The relationship of the sphincter of Oddi to the stomach, duodenum and gall-bladder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6065875", "endSection": "title" }, { "offsetInBeginSection": 727, "offsetInEndSection": 831, "text": "There is a definite relationship between gastric antral activity and flow through the sphincter of Oddi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6065875", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 494, "text": "The sphincter of Oddi appears to be partially autonomous but is readily affected by changes in duodenal tone.2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6065875", "endSection": "abstract" }, { "offsetInBeginSection": 892, "offsetInEndSection": 1021, "text": "Mechanical or electrical stimulation of the stomach, duodenum, or upper small bowel influences the tone of the sphincter of Oddi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6065875", "endSection": "abstract" }, { "offsetInBeginSection": 466, "offsetInEndSection": 582, "text": "Two thirds of patients with biliary sphincter of Oddi dysfunction have elevated pancreatic basal sphincter pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11900681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Major papilla pancreatic sphincter dysfunction, a variant of sphincter of Oddi dysfunction, causes pancreatitis and pancreatic-type pain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11900681", "endSection": "abstract" }, { "offsetInBeginSection": 1027, "offsetInEndSection": 1226, "text": "Biliary and pancreatic endoscopic sphincterotomies are associated with two- to fourfold increased incidence of pancreatitis following the procedure in patients with pancreatic sphincter hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11900681", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "It has been reported that interdigestive motor activities occur in the gallbladder and sphincter of Oddi as well as in the gastroduodenal tract and truncal vagus nerves modulate the gastroduodenal motility pattern.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7549047", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1215, "text": "The results imply that celiac branches of the vagus nerve modulate the interdigestive motor activity in the stomach, descending duodenum, gallbladder and sphincter of Oddi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7549047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The sphincter of Oddi is a small sphincter which is strategically placed at the junction of the bile duct and pancreatic duct with the duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2052626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "[Lesions of the area of Oddi's sphincter: incidence and association with biliary and pancreatic lesions in a series of 109 autopsies].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3653618", "endSection": "title" }, { "offsetInBeginSection": 527, "offsetInEndSection": 801, "text": "These studies support Oddi's original description that the sphincter has a major role in the control of flow of bile and pancreatic juice into the duodenum, and equally importantly helps prevent the reflux of duodenal contents into the biliary and pancreatic ductal systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2666281", "endSection": "abstract" }, { "offsetInBeginSection": 1264, "offsetInEndSection": 1453, "text": "We have used the term sphincter of Oddi dysfunction to define manometric abnormalities in patients who present with signs and symptoms consistent with a biliary or pancreatic ductal origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2666281", "endSection": "abstract" }, { "offsetInBeginSection": 641, "offsetInEndSection": 833, "text": "Chronic pancreatitis was more frequently associated with an abnormal sphincter of Oddi, but in these cases, another associated disease could explain pancreatitis (alcoholism, hemochromatosis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3653618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The sphincter of Oddi (SO) is critically located at the junction of the common bile duct (CBD), main pancreatic duct, and the duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3058076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Sphincter of Oddi (SO) is a dynamic structure located strategically at the confluence of the bile duct, the pancreatic duct and the duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7991969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The most common functional disorder of the biliary tract and pancreas relates to the activity of the Sphincter of Oddi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19799700", "endSection": "abstract" } ] }, { "body": "List clinical phenotypes and molecular genetic features of patients with KMT2B-related disorders", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33150406" ], "ideal_answer": [ "Atypical patterns of dystonia evolution and a subgroup of patients presents with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features there seem to be co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies.", "KMT2B-related disorders result in significant improvement in motor function and disability at 6 months, 1 year, and again at 1 year after stimulation. The greatest improvements are seen for trunk and cervical dystonia, with less clinical impact on laryngeal or transternal dystonias. Patients with chromosomal deletions and protein truncating variants have a higher burden of systemic disease than those with missense variants." ], "exact_answer": [ [ "dystonia evolution" ], [ "non-dystonic neurodevelopmental phenotype" ], [ "risk of status dystonicus" ], [ "intrauterine growth retardation" ], [ "endocrinopathies" ] ], "type": "list", "id": "61f97372882a024a10000051", "snippets": [ { "offsetInBeginSection": 521, "offsetInEndSection": 2944, "text": "We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5-37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden's Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33150406", "endSection": "abstract" } ] }, { "body": "What is the use of Atogepant?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32297990", "http://www.ncbi.nlm.nih.gov/pubmed/33142014", "http://www.ncbi.nlm.nih.gov/pubmed/34521260", "http://www.ncbi.nlm.nih.gov/pubmed/34813050", "http://www.ncbi.nlm.nih.gov/pubmed/34407343", "http://www.ncbi.nlm.nih.gov/pubmed/33369482", "http://www.ncbi.nlm.nih.gov/pubmed/34788240" ], "ideal_answer": [ "Atogepant is used for preventive treatment of migraine." ], "exact_answer": [ "preventive treatment of migraine" ], "type": "factoid", "id": "61f60157882a024a1000001e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34521260", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "BACKGROUND: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34521260", "endSection": "abstract" }, { "offsetInBeginSection": 1452, "offsetInEndSection": 1652, "text": "CONCLUSION: Atogepant demonstrated treatment benefits as early as the first full day after treatment initiation, and sustained efficacy across each 4-week interval during the 12-week treatment period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34521260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 414, "text": "Atogepant (Qulipta\u2122) is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by AbbVie for the prophylaxis of migraine. In September 2021, atogepant was approved in the USA for the preventive treatment of episodic migraine in adults. The drug is also in phase 3 clinical development for the preventive treatment of migraine in various other countries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813050", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 769, "text": "This paper reviews the available data from RCTs to assess the clinical efficacy, safety, and tolerability profile of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine and atogepant for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33369482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Atogepant is a potent, selective, oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for migraine prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33142014", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 334, "text": "Atogepant, a potent, selective antagonist of the calcitonin gene-related peptide receptor-in development for migraine prevention-is thus likely to be used by women taking oral contraceptives.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32297990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Atogepant for the Preventive Treatment of Migraine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34407343", "endSection": "title" }, { "offsetInBeginSection": 189, "offsetInEndSection": 302, "text": "ember 2021, atogepant was approved in the USA for the preventive treatment of episodic migraine in adults. The dr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Atogepant for the Preventive Treatment of Migraine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34407343", "endSection": "title" }, { "offsetInBeginSection": 1083, "offsetInEndSection": 1134, "text": "Atogepant for the Preventive Treatment of Migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Atogepant (Qulipta\u2122) is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by AbbVie for the prophylaxis of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "BACKGROUND: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of migraine.METHODS: In the double-blind, phase 3 ADVANCE trial, participants with 4-14 migraine days/month were randomized to atogepant 10\u2009mg, 30\u2009mg, 60\u2009mg, or placebo onc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34521260", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 295, "text": "In September 2021, atogepant was approved in the USA for the preventive treatment of episodic migraine in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813050", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 576, "text": "This article summarizes the milestones in the development of atogepant leading to this first approval for the preventive treatment of episodic migraine in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34813050", "endSection": "abstract" } ] }, { "body": "Is SMOC2 expressed during wound healing?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33710643", "http://www.ncbi.nlm.nih.gov/pubmed/34876240", "http://www.ncbi.nlm.nih.gov/pubmed/32355542", "http://www.ncbi.nlm.nih.gov/pubmed/32908163" ], "ideal_answer": [ "Yes,\nSMOC2 response to wounding." ], "exact_answer": "yes", "type": "yesno", "id": "621b950f3a8413c653000044", "snippets": [ { "offsetInBeginSection": 1222, "offsetInEndSection": 1536, "text": "All three fibroblast populations were PDGFR\u03b1+/CD34\u00a0+\u00a0but were distinct in their expression of Ngfr/Spon2/Angptl7 (F1), Cxcl14/Smoc2/Rgs2 (F2), and Clec3b/Col14a1/Mmp3 (F3), with potential functions in the regulation of immune responses, response to wounding, and organization of extracellular matrix, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33710643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32908163", "endSection": "title" } ] }, { "body": "What is a potential alternate uses(repositioning) for Primaquine", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28900272", "http://www.ncbi.nlm.nih.gov/pubmed/33787719", "http://www.ncbi.nlm.nih.gov/pubmed/32125014", "http://www.ncbi.nlm.nih.gov/pubmed/34884765", "http://www.ncbi.nlm.nih.gov/pubmed/34149436" ], "ideal_answer": [ "Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization. PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity", "Primaquine could be used as a novel drug for vascular leakage by maintaining endothelial integrity and for", "Primaquine Diphosphate, a known Antimalarial Drug, blocks Vascular Leakage through Junction Stabilization. This is a potential alternate uses." ], "exact_answer": [ [ "Blocks Vascular Leakage" ], [ "anti parasite", "anti Neospora caninum" ] ], "type": "list", "id": "621ecc3e3a8413c653000060", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34149436", "endSection": "title" }, { "offsetInBeginSection": 1153, "offsetInEndSection": 1244, "text": " PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34149436", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 685, "text": "Here, we report that antimalaria drug primaquine phosphate (PRQ) exhibits an anti-leukemia effect on both ATRA-sensitive cell line NB4 and ATRA-resistant APL cell lines, NB4-LR2, NB4-LR1, and NB4-MR2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32125014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Primaquine phosphate induces the apoptosis of ATRA-resistant acute promyelocytic leukemia cells by inhibition of the NF-\u03baB pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32125014", "endSection": "title" }, { "offsetInBeginSection": 248, "offsetInEndSection": 414, "text": "Here, using drug repositioning, we discovered that primaquine diphosphate (PD), previously known as an antimalarial drug, was a potential blocker of vascular leakage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34149436", "endSection": "abstract" }, { "offsetInBeginSection": 558, "offsetInEndSection": 721, "text": "We showed that primaquine, a malaria drug, inhibits the growth, migration, and colony formation of breast cancer cells in vitro, and inhibits tumor growth in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34884765", "endSection": "abstract" }, { "offsetInBeginSection": 926, "offsetInEndSection": 1186, "text": "Moreover, primaquine and chloroquine induce the apoptosis of breast cancer cells through c-Myc/Bcl-2 downregulation, induce early endosome damage and reduce nEGFR levels, and induce apoptosis in breast cancer through nEGFR/Stat3-dependent c-Myc downregulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34884765", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 557, "text": "The aim of the present study was to investigate the effect and mechanism of chloroquine- and primaquine-induced apoptosis of breast cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34884765", "endSection": "abstract" }, { "offsetInBeginSection": 1110, "offsetInEndSection": 1245, "text": "Taken together, these findings suggest that PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34149436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "From malaria to cancer: Computational drug repositioning of amodiaquine using PLIP interaction patterns.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28900272", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Primaquine Inhibits the Endosomal Trafficking and Nuclear Localization of EGFR and Induces the Apoptosis of Breast Cancer Cells by Nuclear EGFR/Stat3-Mediated c-Myc Downregulation", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34884765", "endSection": "title" } ] }, { "body": "Does daily atemoya juice intake change the pharmacokinetics of CYP1A2 substrates?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34881402" ], "ideal_answer": [ "No, atemoya juice does not change the pharmacokinetics of CYP1A2 substrates." ], "exact_answer": "no", "type": "yesno", "id": "620580afc9dfcb9c0900002f", "snippets": [ { "offsetInBeginSection": 838, "offsetInEndSection": 1103, "text": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A. In spite of this inhibition, preadministration of atemoya had no effect on the pharmacokinetics of phenacetin, a CYP1A2 substrate, in rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881402", "endSection": "abstract" }, { "offsetInBeginSection": 1504, "offsetInEndSection": 1679, "text": "The results indicate that a daily intake of atemoya would not change the pharmacokinetics of CYP1A2 substrates such as phenacetin as well as CYP2C9- and CYP3A-substrate drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881402", "endSection": "abstract" } ] }, { "body": "What is caused by gain-of-function variants in SYK?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33782605" ], "ideal_answer": [ "Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice.", "SYK gain-of-function variants cause immune dysregulation and systemic inflammation in humans and mice." ], "type": "summary", "id": "61f86b5b882a024a10000043", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33782605", "endSection": "title" }, { "offsetInBeginSection": 625, "offsetInEndSection": 747, "text": "Our studies demonstrate that SYK gain-of-function variants result in a potentially treatable form of inflammatory disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33782605", "endSection": "abstract" } ] }, { "body": "Is Cabotegravir effective for HIV prevention?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32492704", "http://www.ncbi.nlm.nih.gov/pubmed/27799824", "http://www.ncbi.nlm.nih.gov/pubmed/34482355", "http://www.ncbi.nlm.nih.gov/pubmed/34379922", "http://www.ncbi.nlm.nih.gov/pubmed/34029457", "http://www.ncbi.nlm.nih.gov/pubmed/32462541", "http://www.ncbi.nlm.nih.gov/pubmed/33347943", "http://www.ncbi.nlm.nih.gov/pubmed/30811880", "http://www.ncbi.nlm.nih.gov/pubmed/26633643", "http://www.ncbi.nlm.nih.gov/pubmed/34871188", "http://www.ncbi.nlm.nih.gov/pubmed/29633869", "http://www.ncbi.nlm.nih.gov/pubmed/33740057", "http://www.ncbi.nlm.nih.gov/pubmed/30012774", "http://www.ncbi.nlm.nih.gov/pubmed/31644481", "http://www.ncbi.nlm.nih.gov/pubmed/33112699", "http://www.ncbi.nlm.nih.gov/pubmed/31447590", "http://www.ncbi.nlm.nih.gov/pubmed/33957367", "http://www.ncbi.nlm.nih.gov/pubmed/26049948", "http://www.ncbi.nlm.nih.gov/pubmed/29746267", "http://www.ncbi.nlm.nih.gov/pubmed/26049951", "http://www.ncbi.nlm.nih.gov/pubmed/30445896" ], "ideal_answer": [ "Yes, Cabotegravir is effective for HIV prevention." ], "exact_answer": "yes", "type": "yesno", "id": "61f602a3882a024a1000001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34871188", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "PURPOSE OF REVIEW: Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34871188", "endSection": "abstract" }, { "offsetInBeginSection": 1023, "offsetInEndSection": 1228, "text": "SUMMARY: Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34871188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "OBJECTIVE: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34482355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492704", "endSection": "title" }, { "offsetInBeginSection": 177, "offsetInEndSection": 331, "text": " Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Design and Testing of a Cabotegravir Implant for HIV Prevention.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33347943", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31447590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre-exposure prophylaxis of HIV-1 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30811880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32462541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Long-acting injectable cabotegravir for the prevention of HIV infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31644481", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 298, "text": "BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33740057", "endSection": "abstract" }, { "offsetInBeginSection": 678, "offsetInEndSection": 931, "text": "Areas covered: Here, we review trials of cabotegravir (CAB) as treatment of HIV-1 infection and its potential use as pre-exposure prophylaxis (PrEP) in high risk individuals, including issues around oral lead in and potential resistance emergence. Exper", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29633869", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 559, "text": "frequent dosing. This review focuses on the potential benefits and considerations for the study and use of 2 long-acting injectable agents, cabotegravir (GSK1265744LA, CAB LA) and rilpivirine (TMC278LA, RPV LA), for use as chemoprophylaxis for HIV ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26633643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "An evaluation of cabotegravir for HIV treatment and prevention.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33112699", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Cabotegravir long-acting for HIV-1 prevention.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049951", "endSection": "title" }, { "offsetInBeginSection": 358, "offsetInEndSection": 541, "text": "Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for antiretroviral therapy and preexposure prophylaxis in HIV-2-prevalent settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30012774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27799824", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Long-Acting Cabotegravir for HIV/AIDS Prophylaxis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34029457", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34379922", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Cabotegravir is a novel human immunodeficiency virus integrase enzyme inhibitor used for prevention and treatment of HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33957367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29633869", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Cabotegravir: its potential for antiretroviral therapy and preexposure prophylaxis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29746267", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445896", "endSection": "title" } ] }, { "body": "What is the function of the protein SERT?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34599615", "http://www.ncbi.nlm.nih.gov/pubmed/34506649", "http://www.ncbi.nlm.nih.gov/pubmed/34136961", "http://www.ncbi.nlm.nih.gov/pubmed/34564289", "http://www.ncbi.nlm.nih.gov/pubmed/31822819", "http://www.ncbi.nlm.nih.gov/pubmed/34517785" ], "ideal_answer": [ "SERT is a Serotonin transporter." ], "exact_answer": [ "Serotonin transporter" ], "type": "factoid", "id": "6217e5433a8413c653000032", "snippets": [ { "offsetInBeginSection": 696, "offsetInEndSection": 747, "text": "serotonin and dopamine transporters (SERT and DAT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34136961", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 362, "text": " the transporter proteins for serotonin (SERT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31822819", "endSection": "abstract" }, { "offsetInBeginSection": 461, "offsetInEndSection": 490, "text": " serotonin transporter (SERT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34506649", "endSection": "abstract" }, { "offsetInBeginSection": 418, "offsetInEndSection": 446, "text": "serotonin transporter (SERT)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34517785", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 239, "text": "serotonin receptor (SERT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34564289", "endSection": "abstract" }, { "offsetInBeginSection": 237, "offsetInEndSection": 261, "text": "5-HT transporter (SERT) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599615", "endSection": "abstract" } ] }, { "body": "Are G-quadruplexes(G4) possible drug targets for glioblastoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33213893", "http://www.ncbi.nlm.nih.gov/pubmed/34459951", "http://www.ncbi.nlm.nih.gov/pubmed/28620243", "http://www.ncbi.nlm.nih.gov/pubmed/26845351", "http://www.ncbi.nlm.nih.gov/pubmed/26908447", "http://www.ncbi.nlm.nih.gov/pubmed/24030712" ], "ideal_answer": [ "The 2H2-6M(4)-oxazole telomestatin derivative (6OTD) targets Glioma stem cells through G4 stabilization and promotion of DNA damage responses. Therefore, G4s are promising therapeutic targets for glioblastoma.", "G-quadruplex DNA structures (G4 DNA) are a promising therapeutic target for glioblastoma because of their ability to stabilize DNA damage and promote DNA damage response in response to 6-oxazole 6-methyl-CoA reductase inhibitors (6OTD)." ], "exact_answer": "yes", "type": "yesno", "id": "62211b973a8413c65300006c", "snippets": [ { "offsetInBeginSection": 1204, "offsetInEndSection": 1385, "text": "These observations indicate that 6OTD targets GSCs through G4 stabilization and promotion of DNA damage responses. Therefore, G4s are promising therapeutic targets for glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Targeting glioma stem cells in vivo by a G-quadruplex-stabilizing synthetic macrocyclic hexaoxazole.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620243", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 390, "text": "G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34459951", "endSection": "abstract" }, { "offsetInBeginSection": 1319, "offsetInEndSection": 1385, "text": "Therefore, G4s are promising therapeutic targets for glioblastoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28620243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Guanine-rich oligonucleotides (GROs) are promising therapeutic candidate for cancer treatment and other biomedical application.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24030712", "endSection": "abstract" }, { "offsetInBeginSection": 1173, "offsetInEndSection": 1315, "text": "These findings are valuable to the design and rationale behind the possible targeted drug delivery to specific cellular organelles using GROs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24030712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "The G-quadruplex (G4) DNA, which has been developed as a potential anticancer target in drug screening and design, plays a crucial role in the oncogene transcription and translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33213893", "endSection": "abstract" }, { "offsetInBeginSection": 1647, "offsetInEndSection": 1750, "text": "Therefore, a novel G4-directed therapeutic strategy could specifically target cancer stem cells in GBM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26845351", "endSection": "abstract" } ] }, { "body": "Is RUNX1T1 associate with obesity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32589708" ], "ideal_answer": [ "Yes, the rs34269950 SNP of the RUNX1T1 gene was significantly associated with obesity risk and metabolic abnormalities. Specifically, compared to AA genotype, rs34269950 del/del genotype was associated with a 1.47 [95% confidence interval (CI): 1.01-2.14, P\u2009=\u20090.042] fold higher rate of obesity risk." ], "exact_answer": "yes", "type": "yesno", "id": "622608ea3a8413c653000079", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "RUNX1T1 rs34269950 is associated with obesity and metabolic syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589708", "endSection": "title" }, { "offsetInBeginSection": 651, "offsetInEndSection": 1060, "text": "Of these SNPs only rs34269950 located in the 'RRACH' motif, the most common N6-methyladenosine (m6A) methylation modification site (recognized by FTO), was significantly associated with obesity risk and metabolic abnormalities. Specifically, compared to AA genotype, rs34269950 del/del genotype was associated with a 1.47 [95% confidence interval (CI): 1.01-2.14, P\u2009=\u20090.042] fold higher rate of obesity risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589708", "endSection": "abstract" }, { "offsetInBeginSection": 1422, "offsetInEndSection": 1571, "text": "Our study demonstrates that RUNX1T1 rs34269950, located in a potential FTO recognition motif, is significantly associated with waist circumference. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589708", "endSection": "abstract" } ] }, { "body": "Is Adamts18 deficiency associated with cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28145888" ], "ideal_answer": [ "Yes. ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. Adamts18 deficiency enhances tumorigenesis and intestinal inflammation through elevated Wnt/\u03b2-catenin and p38MAPK/ERK1/2 signaling and promotes colon cancer in this mouse model." ], "exact_answer": "yes", "type": "yesno", "id": "61f9cb19c9dfcb9c09000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Adamts18 deficiency promotes colon carcinogenesis by enhancing \u03b2-catenin and p38MAPK/ERK1/2 signaling in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28145888", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1074, "text": "ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. However, the underlying mechanism is not clear. Here we generated an Adamts18-deficient mouse strain as an in vivo model to investigate the role of ADAMTS18 in the pathogenesis of colorectal cancer. In AOM/DSS-induced colitis-associated colorectal cancer, the deficiency of Adamts18 in mice resulted in enhanced tumorigenesis and colon inflammation that could be attributed in part to enhanced nuclear translocation of \u03b2-catenin and elevated expression of its downstream target genes, cyclin D1 and c-myc. Moreover, increased p38MAPK and ERK1/2 activities were detected in colon cancer cells from Adamts18-deficient mice. Further studies revealed that ADAMTS18 deficiency reduced intestinal E-cadherin levels in mice, which ultimately led to intestinal barrier dysfunction. These data indicate that Adamts18 deficiency enhances tumorigenesis and intestinal inflammation through elevated Wnt/\u03b2-catenin and p38MAPK/ERK1/2 signaling and promotes colon cancer in this mouse model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28145888", "endSection": "abstract" } ] }, { "body": "What causes Ocular Thelaziasis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30349847", "http://www.ncbi.nlm.nih.gov/pubmed/29087095", "http://www.ncbi.nlm.nih.gov/pubmed/24399399", "http://www.ncbi.nlm.nih.gov/pubmed/30672496", "http://www.ncbi.nlm.nih.gov/pubmed/28710682", "http://www.ncbi.nlm.nih.gov/pubmed/25116781", "http://www.ncbi.nlm.nih.gov/pubmed/17211660" ], "ideal_answer": [ "Ocular Thelaziasis is caused by Thelazia callipaeda." ], "exact_answer": [ "Thelazia callipaeda" ], "type": "factoid", "id": "61f5fcb6882a024a1000001b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Human ocular thelaziasis caused by gravid Thelazia callipaeda - A unique and rare case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30672496", "endSection": "title" }, { "offsetInBeginSection": 180, "offsetInEndSection": 542, "text": "We report the first case of human ocular thelaziasis in Nepal in a 6-month-old child from a Rukum district, Nepal. The infant presented with conjunctivitis, and his visual acuity and dilated fundal examination were normal. A total of 6 worms were removed for identification. Collected nematodes were identified based on morphological keys as Thelazia callipaeda.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30349847", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Thelaziasis is an arthropod-born disease of the eye and adnexa caused by Thelazia callipaeda, a nematode parasite transmitted by drosophilid flies to carnivores and humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Thelaziasis is an arthropod-born disease of the eye and adnexa caused by Thelazia callipaeda, a nematode parasite transmitted by drosophilid flies to carnivores and humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25116781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Thelazia callipaeda is the main causative organism in thelaziasis, commonly infecting orbital cavities and associated tissues of carnivores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28710682", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 225, "text": "Thelaziasis is a zoonosis caused by\nnematodes of the genus Thelazia, parasites of the conjunctival bags or tear ducts of mammals and birds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29087095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Human ocular thelaziasis caused by gravid Thelazia callipaeda - A unique ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30672496", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND: Thelazia callipaeda is the main causative organism in thelaziasis, commonly infecting orbital cavities and associated tissues of", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28710682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Thelaziasis is an ocular infection of several mammals caused by nematodes of the genus Thelazia (Spirurida, Thelaziidae).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17211660", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Human thelaziasis is a zoonotic eye disease caused by a nematode parasite called Thelazia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24399399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Thelaziasis is an ocular arthropod-borne, zoonotic disease of the eye infecting the conjunctival sac, lacrimal duct, and lacrimal gland caused by a nematode of the genus Thelazia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30349847", "endSection": "abstract" } ] }, { "body": "What is the role of cytidine deaminase in healthy cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34819671", "http://www.ncbi.nlm.nih.gov/pubmed/34819670", "http://www.ncbi.nlm.nih.gov/pubmed/32729075", "http://www.ncbi.nlm.nih.gov/pubmed/34528388", "http://www.ncbi.nlm.nih.gov/pubmed/32729074" ], "ideal_answer": [ "Activation-induced cytidine deaminase (AID) catalyses the deamination of deoxycytidines to deoxyuracils within immunoglobulin genes to induce somatic hypermutation and class-switch recombination." ], "exact_answer": [ "deamination of deoxycytidines" ], "type": "factoid", "id": "6217d8973a8413c653000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "The AID/APOBEC family of enzymes are cytidine deaminases that act upon DNA and RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32729074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "APOBEC1 is a member of the AID/APOBECs, a group of deaminases responsible for the editing of C>U in both DNA and RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32729075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "The human genome contains 11 APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) cytidine deaminases classified into four families. These proteins function mainly in innate antiviral immunity and can also restrict endogenous retrotransposable element multiplication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34528388", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Activation-induced cytidine deaminase (AID) catalyses the deamination of deoxycytidines to deoxyuracils within immunoglobulin genes to induce somatic hypermutation and class-switch recombination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 411, "text": "Efficient humoral responses rely on DNA damage, mutagenesis and error-prone DNA repair. Diversification of B cell receptors through somatic hypermutation and class-switch recombination are initiated by cytidine deamination in DNA mediated by activation-induced cytidine deaminase\u00a0(AID)1 and by the subsequent excision of the resulting uracils by uracil DNA glycosylase (UNG) and by mismatch repair proteins1-3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819671", "endSection": "abstract" } ] }, { "body": "Summarize the cause of autosomal dominant Spinocerebellar Ataxia type 3.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32266540", "http://www.ncbi.nlm.nih.gov/pubmed/31639609", "http://www.ncbi.nlm.nih.gov/pubmed/15316156", "http://www.ncbi.nlm.nih.gov/pubmed/9629399", "http://www.ncbi.nlm.nih.gov/pubmed/34159894", "http://www.ncbi.nlm.nih.gov/pubmed/34535635", "http://www.ncbi.nlm.nih.gov/pubmed/9048937", "http://www.ncbi.nlm.nih.gov/pubmed/33219521", "http://www.ncbi.nlm.nih.gov/pubmed/26123252", "http://www.ncbi.nlm.nih.gov/pubmed/34565721", "http://www.ncbi.nlm.nih.gov/pubmed/32346735" ], "ideal_answer": [ "Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3.", "Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3." ], "type": "summary", "id": "621fca543a8413c653000064", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 151, "text": " Spinocerebellar ataxias (SCAs) are rare dominantly inherited neurodegenerative disorders that lead to severe disability and premature death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32266540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535635", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 318, "text": "Spinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant ataxias in the world. Several reports revealed that CAG repeats in some polyQ-containing genes may affect the age at onset (AAO) of patients with SCA2, however, little studies were conducted among Chinese patients with SCA2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34565721", "endSection": "abstract" }, { "offsetInBeginSection": 1941, "offsetInEndSection": 2035, "text": "The CAG repeat in ATXN2 is a major genetic factor for the AAO of patients with SCA2 in China. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34565721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33219521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Spinocerebellar Ataxia (SCA) is a heterogeneous adult-onset disorder with an autosomal dominant inheritance pattern mainly caused by triplet repeat expansions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34159894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 326, "text": "Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9629399", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type 3, SCA3), an autosomal dominant neurological disorder, is caused by an abnormal expanded polyglutamine (polyQ) repeat in the ataxin-3 protein. The l", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26123252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Spinocerebellar ataxia type 3 (SCA3), also known by the eponym Machado-Joseph disease, is an autosomal dominant CAG trinucleotide (polyglutamine) repeat disease that presents in young- to middle-aged adults. SCA3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32346735", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Machado-Joseph disease (MJD) is the most common type of autosomal dominant spinocerebellar ataxia caused by an expanded CAG repeat in the MJD1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15316156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant disorder that is caused by the abnormal amplification of cytosine-adenine-guanine (CAG) trinucleotide repeats in the ATXN3 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31639609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Spinocerebellar ataxia type 1 and type 3 (SCA1, SCA3) are autosomal dominant neurodegenerative disorders caused by expanded CAG trinucleotide repeats in novel genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9048937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Spinocerebellar ataxia type 3 (SCA3), also known by the eponym Machado-Joseph disease, is an autosomal dominant CAG trinucleotide (polyglutamine) repeat disease that presents in young- to middle-aged adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32346735", "endSection": "abstract" } ] }, { "body": "Through which pathway does the FTO-guided demethylation of GADD46 drive myogenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34513292" ], "ideal_answer": [ "FTO-mediated demethylation of GADD45B promotes myogenesis through the activation of p38 MAPK pathway." ], "exact_answer": [ "p38 MAPK pathway" ], "type": "factoid", "id": "622628b03a8413c65300007d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "FTO-mediated demethylation of GADD45B promotes myogenesis through the activation of p38 MAPK pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34513292", "endSection": "title" }, { "offsetInBeginSection": 1177, "offsetInEndSection": 1418, "text": "Our results indicate that the FTO-mediated m6A modification in GADD45B mRNA drives skeletal muscle differentiation by activating the p38 MAPK pathway, which provides a molecular mechanism for the regulation of myogenesis via RNA methylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34513292", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 868, "text": "Moreover, the expression of GADD45B regulates the expression of\u00a0myogenic regulatory factors and peroxisome proliferator-activated receptor gamma coactivator 1 alpha by activating the p38 mitogen-activated protein kinase (MAPK) pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34513292", "endSection": "abstract" } ] }, { "body": "What are the key characteristics of the syndrome caused by ANKRD17 loss-of-function variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33909992" ], "ideal_answer": [ "Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphia.", "Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism.", "Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism, as well as growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy, and/or abnormal EEG, and predisposition to recurrent infections." ], "exact_answer": [ [ "Intellectual disability" ], [ "Speech delay" ], [ "Dysmorphism" ] ], "type": "list", "id": "61f81a2d882a024a10000042", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33909992", "endSection": "title" }, { "offsetInBeginSection": 576, "offsetInEndSection": 1658, "text": "Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33909992", "endSection": "abstract" } ] }, { "body": "Is Ozanimod effective for Ulcerative Colitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33438008", "http://www.ncbi.nlm.nih.gov/pubmed/34423657", "http://www.ncbi.nlm.nih.gov/pubmed/34587385", "http://www.ncbi.nlm.nih.gov/pubmed/27144850", "http://www.ncbi.nlm.nih.gov/pubmed/29608575", "http://www.ncbi.nlm.nih.gov/pubmed/29766731", "http://www.ncbi.nlm.nih.gov/pubmed/27049060" ], "ideal_answer": [ "Yes, Ozanimod is effective for Ulcerative Colitis." ], "exact_answer": "yes", "type": "yesno", "id": "61f5f89b882a024a10000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587385", "endSection": "title" }, { "offsetInBeginSection": 2204, "offsetInEndSection": 2361, "text": "CONCLUSIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587385", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1659, "text": "CONCLUSIONS: There was a high rate of continued study participation and long-term benefit with ozanimod HCl 1 mg daily based on clinical, histological and biomarker measures in patients with moderately to severely active UC in the TOUCHSTONE OLE. [NCT02531126].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33438008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34423657", "endSection": "title" }, { "offsetInBeginSection": 1526, "offsetInEndSection": 1604, "text": "CONCLUSION: Ozanimod is another option in the growing arsenal of UC treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34423657", "endSection": "abstract" }, { "offsetInBeginSection": 1125, "offsetInEndSection": 1341, "text": "RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Ozanimod is the first sphingosine 1-phosphate modulator to be approved for UC and is administered orally. Its efficacy profile is comparable with other UC medications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34423657", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 1016, "text": "Compared with placebo, ozanimod led to clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. Additionally, for secondary end points of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing, ozanimod performed significantly better than placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34423657", "endSection": "abstract" }, { "offsetInBeginSection": 1221, "offsetInEndSection": 1459, "text": "Ozanimod interferes with migrations of activated T cells to the site of inflammation and is a promising drug for the UC treatment.Key words: Crohns disease - mongersen - monoclonal antibodies - ozanimod - tofacitinib - ulcerative colitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29766731", "endSection": "abstract" }, { "offsetInBeginSection": 2210, "offsetInEndSection": 2367, "text": "SIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Fund", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27049060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Ozan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608575", "endSection": "abstract" }, { "offsetInBeginSection": 2210, "offsetInEndSection": 2366, "text": "SIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Fun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587385", "endSection": "abstract" }, { "offsetInBeginSection": 2148, "offsetInEndSection": 2312, "text": "SIONS: In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27144850", "endSection": "abstract" } ] }, { "body": "What is the function of the protein PIEZO1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34766984", "http://www.ncbi.nlm.nih.gov/pubmed/34687906", "http://www.ncbi.nlm.nih.gov/pubmed/34548087", "http://www.ncbi.nlm.nih.gov/pubmed/34489534" ], "ideal_answer": [ "Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca2+ influx, which in turn regulates cytoskeletal remodeling and stress alterations." ], "exact_answer": [ "mechanotransduction process" ], "type": "factoid", "id": "621d02f33a8413c653000047", "snippets": [ { "offsetInBeginSection": 35, "offsetInEndSection": 75, "text": "the mechanosensitive ion channel Piezo1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34687906", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 731, "text": "mechanosensitive Piezo1 channels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34766984", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 428, "text": "mechanosensitive Piezo1 channels", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34489534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 38, "text": "Mechanosensitive cation channel Piezo1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548087", "endSection": "title" }, { "offsetInBeginSection": 127, "offsetInEndSection": 344, "text": "Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca2+ influx, which in turn regulates cytoskeletal remodeling and stress alterations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548087", "endSection": "abstract" } ] }, { "body": "Please list 3 biologic(monoclonal antibody) drugs used to treat migraine headaches.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31122188", "http://www.ncbi.nlm.nih.gov/pubmed/28240610", "http://www.ncbi.nlm.nih.gov/pubmed/33363597", "http://www.ncbi.nlm.nih.gov/pubmed/33856626", "http://www.ncbi.nlm.nih.gov/pubmed/29616494", "http://www.ncbi.nlm.nih.gov/pubmed/32145209", "http://www.ncbi.nlm.nih.gov/pubmed/29722276", "http://www.ncbi.nlm.nih.gov/pubmed/33542885", "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "http://www.ncbi.nlm.nih.gov/pubmed/34246226", "http://www.ncbi.nlm.nih.gov/pubmed/33765912", "http://www.ncbi.nlm.nih.gov/pubmed/26879279", "http://www.ncbi.nlm.nih.gov/pubmed/26432182", "http://www.ncbi.nlm.nih.gov/pubmed/34742252", "http://www.ncbi.nlm.nih.gov/pubmed/30413151", "http://www.ncbi.nlm.nih.gov/pubmed/31985655", "http://www.ncbi.nlm.nih.gov/pubmed/33023473", "http://www.ncbi.nlm.nih.gov/pubmed/30106172", "http://www.ncbi.nlm.nih.gov/pubmed/31020659", "http://www.ncbi.nlm.nih.gov/pubmed/33892641", "http://www.ncbi.nlm.nih.gov/pubmed/31050694", "http://www.ncbi.nlm.nih.gov/pubmed/29171818", "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "http://www.ncbi.nlm.nih.gov/pubmed/34115380", "http://www.ncbi.nlm.nih.gov/pubmed/34363708", "http://www.ncbi.nlm.nih.gov/pubmed/30886915", "http://www.ncbi.nlm.nih.gov/pubmed/34544359" ], "ideal_answer": [ " Large molecule biologic antibody (mAb) approaches that are given subcutaneously to neutralize circulating CGRP peptide (fremanezumab, galcanezumab) or block CGRP receptors (erenumab) have shown consistent efficacy and tolerability in multicenter migraine prevention trials and are now approved for clinical use.", "Large molecule biologic antibody (mAb) approaches that are given subcutaneously to neutralize circulating CGRP peptide (fremanezumab, galcanezumab) or block CGRP receptors (erenumab) have shown consistent efficacy and tolerability in multicenter migraine prevention trials and are now approved for clinical use." ], "exact_answer": [ [ "fremanezumab" ], [ "galcanezumab" ], [ "erenumab", "aimovig" ], [ "Eptinezumab" ] ], "type": "list", "id": "601dbeb31cb411341a00004e", "snippets": [ { "offsetInBeginSection": 1517, "offsetInEndSection": 1829, "text": " Large molecule biologic antibody (mAb) approaches that are given subcutaneously to neutralize circulating CGRP peptide (fremanezumab, galcanezumab) or block CGRP receptors (erenumab) have shown consistent efficacy and tolerability in multicenter migraine prevention trials and are now approved for clinical use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31020659", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1161, "text": "Since 2004, mAbs have been used to treat several neurological diseases, yielding new therapeutic perspectives: natalizumab, alemtuzumab and ocrelizumab for multiple sclerosis, eculizumab for myasthenia gravis, erenumab and frenazumab for migraine, galcanezumab for migraine and cluster headache, eculizumab for neuromyelitis optica spectrum disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33363597", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "INTRODUCTION: Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33856626", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171818", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 212, "text": "Erenumab is a novel CGRP-receptor antibody with preventive efficacy in migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30360965", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 278, "text": "Here we assess the safety, tolerability, and efficacy of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of high-frequency episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26432182", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 421, "text": "abotulinumtoxinA (BoNT-A) has become a very popular medication for treating migraine headaches in those cases in which other medication is not working, typically in chronic migraines. Cur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30886915", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 336, "text": " per year. OnabotulinumtoxinA (botulinum toxin type A) is a U.S. Food and Drug Administration-approved prophylactic medication for chronic migraine headaches and is best injected in a targeted fashion into specific trig", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31985655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "On September 15, 2018, the U.S. Food and Drug Administration (FDA) approved subcutaneous fremanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody, for the treatment of episodic and chronic migraine in adults, with two recommended dosages: 225 mg monthly or 675 mg every 3 months. On March", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31050694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "BACKGROUND: Calcitonin gene-related peptide (CGRP) (receptor) antibodies (erenumab, fremanezumab and galcanezumab) are increasingly used in prophylactic treatment of mig", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34544359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Both calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and OnabotulinumtoxinA (botox) are used in the prevention of chronic migraines. Howe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33542885", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Objective - To evaluate 12-week changes from baseline of 2 disease-specific patient-reported outcome (PRO) measures in adults with migraine treated with galcanezumab, an investigational humanized antibody binding calcitonin gene-related peptide (CGRP), or placebo. Bac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30106172", "endSection": "abstract" }, { "offsetInBeginSection": 528, "offsetInEndSection": 788, "text": "eceptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. As these d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: In phase 2 and 3 studies, fremanezumab, a monoclonal CGRP antibody, was an effective preventive treatment for high-frequency episodic migraine (HFEM) and chronic migrai", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29722276", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 293, "text": "2018;38:1442-1454), which substantially changed the level of evidence of galcanezumab for the prevention of episodic migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31122188", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Real-world evidence data on the monoclonal antibody erenumab in migraine prevention: perspectives of treating physicians in Germany.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34742252", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "PURPOSE OF REVIEW: The results of phase 2 randomized controlled trials for the prevention of episodic and chronic migraine demonstrating the efficacy and safety of four mAbs targeting the calcitonin gene-related peptide (CGRP) pathway [ALD403 (eptinezumab), AMG334 (erenumab), LY2951742 (galcanezumab) and TEV48125 (fremanezumab)] have been published recently, and phase 3 tri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28240610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29171818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33765912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND: Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33892641", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 359, "text": "Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29616494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "BACKGROUND: Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (\u22646-month of treatment) a reduction in the number of migraine headache days and improved patients' ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30413151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (IgG2\u0394a) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34246226", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 747, "text": "h migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention.METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26879279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 746, "text": "BACKGROUND: In phase 2 and 3 studies, fremanezumab, a monoclonal CGRP antibody, was an effective preventive treatment for high-frequency episodic migraine (HFEM) and chronic migraine (CM).OBJECTIVE: Post-hoc analyses evaluated population-wise 50%, 75% and 100% responder rates, and the extent to which individual responders sustained a 50%, 75% and 100% reduction in migraine days, moderate-to-severe (M/S) headache days and days of acute medication use during all three treatment months of the fremanezumab phase 2 studies.DESIGN/METHODS: HFEM patients received either placebo or three once-monthly injections of 225\u2009mg or 675\u2009mg. CM patients received either placebo or three once-monthly injections of 900\u2009mg, or an initial loading dose of 675\u2009", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29722276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 473, "text": "OBJECTIVE: To evaluate the impact of fremanezumab on the severity and duration of remaining migraine attacks in patients with chronic migraine (CM) or episodic migraine (EM).BACKGROUND: Fremanezumab is a fully humanized monoclonal antibody (IgG\u0394a) that selectively targets calcitonin gene-related peptide and is efficacious in reducing migraine frequency.METHODS: This exploratory post hoc analysis included data from three randomized, double-blind, 12-week, phase 3 studie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34115380", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 450, "text": "The Food and Drug Administration (FDA) recently approved 3 new humanized monoclonal antibodies that target calcitonin gene-related peptide (CGRP): erenumab, fremanezumab, and galcanezumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32145209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "BACKGROUND: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide-targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chron", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33023473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND: Erenumab is a human anti-calcitonin gene-related peptide receptor monoclonal antibody approved for migraine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34363708", "endSection": "abstract" }, { "offsetInBeginSection": 451, "offsetInEndSection": 603, "text": "The agents either bind to the CGRP receptor (erenumab) or bind to the CGRP ligand (fremanezumab and galcanezumab) and block its binding to the receptor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32145209", "endSection": "abstract" } ] }, { "body": "What is the most common N6-methyladenosine (m6A) methylation modification site of RUNX1T1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32589708" ], "ideal_answer": [ "The RRACH motif is the most common N6-methyladenosine (m6A) methylation modification site of RUNX1T1." ], "exact_answer": [ "RRACH motif" ], "type": "factoid", "id": "622627103a8413c65300007c", "snippets": [ { "offsetInBeginSection": 651, "offsetInEndSection": 879, "text": "Of these SNPs only rs34269950 located in the 'RRACH' motif, the most common N6-methyladenosine (m6A) methylation modification site (recognized by FTO), was significantly associated with obesity risk and metabolic abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589708", "endSection": "abstract" } ] }, { "body": "Describe GREEKC", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34757206" ], "ideal_answer": [ "The COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC, CA15205, www.greekc.org) organized nine workshops in a four-year period, starting September 2016. The workshops brought together experts from all over the world working on various steps in the knowledge management process that focuses on understanding gene regulatory mechanisms.", "As computational modeling becomes more essential to analyze and understand biological regulatory mechanisms, governance of the many databases and knowledge bases that support this domain is crucial to guarantee reliability and interoperability of resources. To address this, the COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC, CA15205, www.greekc.org) organized nine workshops in a four-year period, starting September 2016. The workshops brought together a wide range of experts from all over the world working on various steps in the knowledge management process that focuses on understanding gene regulatory mechanisms. The discussions between ontologists, curators, text miners, biologists, bioinformaticians, philosophers and computational scientists spawned a host of activities aimed to standardize and update existing knowledge management workflows and involve end-users in the process of designing the Gene Regulation Knowledge Commons (GRKC)." ], "type": "summary", "id": "61f9c990c9dfcb9c09000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1066, "text": "As computational modeling becomes more essential to analyze and understand biological regulatory mechanisms, governance of the many databases and knowledge bases that support this domain is crucial to guarantee reliability and interoperability of resources. To address this, the COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC, CA15205, www.greekc.org) organized nine workshops in a four-year period, starting September 2016. The workshops brought together a wide range of experts from all over the world working on various steps in the knowledge management process that focuses on understanding gene regulatory mechanisms. The discussions between ontologists, curators, text miners, biologists, bioinformaticians, philosophers and computational scientists spawned a host of activities aimed to standardize and update existing knowledge management workflows and involve end-users in the process of designing the Gene Regulation Knowledge Commons (GRKC). Here the GREEKC consortium describes its main achievements in improving this GRKC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34757206", "endSection": "abstract" } ] }, { "body": "Which receptors are targeted by Tirzepatide?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34542221", "http://www.ncbi.nlm.nih.gov/pubmed/32291277", "http://www.ncbi.nlm.nih.gov/pubmed/32519795", "http://www.ncbi.nlm.nih.gov/pubmed/33236115", "http://www.ncbi.nlm.nih.gov/pubmed/34431633", "http://www.ncbi.nlm.nih.gov/pubmed/34626443", "http://www.ncbi.nlm.nih.gov/pubmed/34518444", "http://www.ncbi.nlm.nih.gov/pubmed/34003802", "http://www.ncbi.nlm.nih.gov/pubmed/33778934", "http://www.ncbi.nlm.nih.gov/pubmed/34819089", "http://www.ncbi.nlm.nih.gov/pubmed/34608929", "http://www.ncbi.nlm.nih.gov/pubmed/34370970", "http://www.ncbi.nlm.nih.gov/pubmed/34170647", "http://www.ncbi.nlm.nih.gov/pubmed/32730231", "http://www.ncbi.nlm.nih.gov/pubmed/33325008", "http://www.ncbi.nlm.nih.gov/pubmed/33030356", "http://www.ncbi.nlm.nih.gov/pubmed/34681215" ], "ideal_answer": [ "Tirzepatide is dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide." ], "exact_answer": [ [ "glucose-dependent insulinotropic polypeptide" ], [ "glucagon-like peptide-1" ] ], "type": "list", "id": "61f6055b882a024a10000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: A post hoc analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34542221", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "In a phase 2 trial of once-weekly tirzepatide (1, 5, 10, or 15\u2009mg), dulaglutide (1.5\u2009mg), or placebo, the dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide dose-dependently reduced HbA1c and body weight in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34542221", "endSection": "abstract" }, { "offsetInBeginSection": 1060, "offsetInEndSection": 1277, "text": "Tirzepatide, a glucose-insulin peptide and GLP-1 dual agonist is in phase 3 study for obesity management, and bimagrumab is a new agent in phase 2 with a unique mechanism of action; they are generating much interest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34518444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects with Type 2 Diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34608929", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819089", "endSection": "title" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1193, "text": "In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819089", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1669, "text": "Tirzepatide and additional dual GLP-1/GIP receptor agonists that could eventually be developed in the future seem to be a promising furthest advance for the management of several cardiometabolic settings. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type\u00a02 Diabetes: The SURPASS Clinical Trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33325008", "endSection": "title" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1018, "text": "Tirzepatide is a novel dual GIP/GLP-1 receptor agonist formulated as a synthetic peptide containing 39\u00a0amino acids, based on the native GIP sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33325008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236115", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "CONTEXT: Novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236115", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 322, "text": "However, the mechanism by which tirzepatide improves efficacy and how GIP receptor (GIPR) agonism contributes is not fully understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34003802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730231", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1 receptor agonists.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32519795", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic steatohepatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Tirzepatide is a dual gastric inhibitory peptide/glucagon-like peptide 1 (GIP/GLP-1) receptor agonist formulated as a synthetic linear peptide, based on the native GIP sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34626443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The new dual gastric inhibitory peptide/glucagon-like peptide 1 agonist tirzepatide in type 2 diabetes: Is the future bright?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34626443", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "The effect of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide on gastric emptying (GE) was compared to that of GLP-1RAs in non-clinical and clinical studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32519795", "endSection": "abstract" }, { "offsetInBeginSection": 398, "offsetInEndSection": 835, "text": "Three approaches may be considered to potentiate weight loss: an increase of the drug dosage because of the demonstration of a dose-response, an add-on therapy with a sodium-glucose cotransporter type 2 inhibitor as this agent exerts a complementary action through urinary calorie loss (glucosuria) or a combination of the effects of two incretin hormones (GLP-1 and GIP), as the potent dual agonist tirzepatide currently in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431633", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 320, "text": "Early phase trials in T2DM indicate that tirzepatide improves clinical outcomes beyond those achieved by a selective GLP-1 receptor agonist.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34170647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, currently under trial to assess glycemic efficacy and safety in people with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34681215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34170647", "endSection": "abstract" }, { "offsetInBeginSection": 1080, "offsetInEndSection": 1208, "text": "k, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. Administered as", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "OBJECTIVE: To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with type 2 diabetes melli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32291277", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1091, "text": "Pharmacologically, signaling studies demonstrate that tirzepatide mimics the actions of native GIP at the GIP receptor but shows bias at the GLP-1 receptor to favor cAMP generation over \u03b2-arrestin recruitment, coincident with a weaker ability to drive GLP-1 receptor internalization compared with GLP-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 388, "text": "BACKGROUND AND AIMS: The pharmacokinetics (PK) and single-dose tolerability of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist being developed for once-weekly treatment of type 2 diabetes (T2D), weight management, and nonalcoholic steatohepatitis, was evaluated in subjects with renal impairment versus healthy subjects with n", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33778934", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 547, "text": "nts with T2D.AREAS COVERED: Tirzepatide is an unimolecular dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA in developme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33030356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "OBJECTIVE: To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with type 2 diabetes mellitus (T2DM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32291277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Tirzepatide (LY3298176), a dual GIP and GLP-1 receptor (GLP-1R) agonist, delivered superior glycemic control and weight loss compared with GLP-1R agonism in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34003802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34170647", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1192, "text": "In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819089", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 787, "text": "This analysis reveals a greater degree of engagement of tirzepatide for the GIP receptor than the GLP-1 receptor, corroborating an imbalanced mechanism of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND: Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist under development for the treatment of type", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34370970", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1284, "text": "Experiments in primary islets reveal \u03b2-arrestin1 limits the insulin response to GLP-1, but not GIP or tirzepatide, suggesting that the biased agonism of tirzepatide enhances insulin secretion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730231", "endSection": "abstract" } ] }, { "body": "Is esophageal adenocarcinoma associated with aberrant glycosylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19441788", "http://www.ncbi.nlm.nih.gov/pubmed/22223758", "http://www.ncbi.nlm.nih.gov/pubmed/23576690", "http://www.ncbi.nlm.nih.gov/pubmed/24957772", "http://www.ncbi.nlm.nih.gov/pubmed/33303693", "http://www.ncbi.nlm.nih.gov/pubmed/20412957" ], "ideal_answer": [ "Yes,\nAltered glycoprotein expression has been demonstrated in tissue from patients with Barrett's esophagus and esophageal cancer but the mechanisms regarding such changes are unknown." ], "exact_answer": "yes", "type": "yesno", "id": "621bd38d3a8413c653000046", "snippets": [ { "offsetInBeginSection": 100, "offsetInEndSection": 280, "text": "Altered glycoprotein expression has been demonstrated in tissue from patients with Barrett's esophagus and esophageal cancer but the mechanisms regarding such changes are unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22223758", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 1156, "text": "Esophageal adenocarcinoma represents a highly morbid and mortal cancer with a defined progression from metaplasia (Barrett's esophagus) to dysplasia to neoplasia. This disease is highlighted because (1) differences in glycan profiles between the stages of disease progression have been described in the glycoproteomic literature; (2) a glycan biomarker that identifies a given stage may be used as a predictor of disease progression and thus may have significant influence over clinical management; and (3) the differences in glycan profiles between disease and disease-free states in esophageal cancer are more dramatic than in other cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24957772", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1177, "text": " comparative glycomic profiling of EAC reveals a subset of glycans that can be selected as candidate biomarkers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19441788", "endSection": "abstract" }, { "offsetInBeginSection": 1580, "offsetInEndSection": 1713, "text": " comparative glycomic profiling of esophageal adenocarcinoma reveals a subset of glycans that can be selected as candidate biomarkers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20412957", "endSection": "abstract" }, { "offsetInBeginSection": 1017, "offsetInEndSection": 1179, "text": "IgG glycosylation profile was independently associated with esophageal precancerosis beyond inflammation, which could be an early biomarker for esophageal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33303693", "endSection": "abstract" } ] }, { "body": "What is the function of a chaperonin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14634002", "http://www.ncbi.nlm.nih.gov/pubmed/26492771", "http://www.ncbi.nlm.nih.gov/pubmed/11295228", "http://www.ncbi.nlm.nih.gov/pubmed/19843217", "http://www.ncbi.nlm.nih.gov/pubmed/28731469", "http://www.ncbi.nlm.nih.gov/pubmed/9337202", "http://www.ncbi.nlm.nih.gov/pubmed/18511909", "http://www.ncbi.nlm.nih.gov/pubmed/22297519", "http://www.ncbi.nlm.nih.gov/pubmed/12354605", "http://www.ncbi.nlm.nih.gov/pubmed/25986150", "http://www.ncbi.nlm.nih.gov/pubmed/30484157", "http://www.ncbi.nlm.nih.gov/pubmed/29696145", "http://www.ncbi.nlm.nih.gov/pubmed/28961247", "http://www.ncbi.nlm.nih.gov/pubmed/30484150", "http://www.ncbi.nlm.nih.gov/pubmed/28963798", "http://www.ncbi.nlm.nih.gov/pubmed/21702926", "http://www.ncbi.nlm.nih.gov/pubmed/15362106", "http://www.ncbi.nlm.nih.gov/pubmed/21265753", "http://www.ncbi.nlm.nih.gov/pubmed/10380224", "http://www.ncbi.nlm.nih.gov/pubmed/15677470", "http://www.ncbi.nlm.nih.gov/pubmed/17489689" ], "ideal_answer": [ "Molecular chaperones promote the correct folding of proteins in aggregation-prone cellular environments by stabilizing nascent polypeptide chains and providing appropriate folding conditions. They are involved in the development of pathological processes, including--atherosclerosis and coronary heart disease.", "Chaperonins assist in the acquisition of native protein structure in the cell by providing a shielded environment for a folding polypeptide chain, generated by the interior surface of their cylindrical structure.", "Molecular chaperones promote the correct folding of proteins in aggregation-prone cellular environments by stabilizing nascent polypeptide chains and providing appropriate folding conditions." ], "type": "summary", "id": "601f0c161cb411341a00006e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Molecular chaperones promote the correct folding of proteins in aggregation-prone cellular environments by stabilizing nascent polypeptide chains and providing appropriate folding conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30484150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Chaperonins assist in the acquisition of native protein structure in the cell by providing a shielded environment for a folding polypeptide chain, generated by the interior surface of their cylindrical structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15362106", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 343, "text": "he folding chain is isolated from the highly crowded cytoplasm, but at the same time confined within the chaperonin folding cage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15362106", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "In review provides information about the function oft the body of chaperones and their role in the development of pathological processes, including--atherosclerosis and coronary heart disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26492771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Molecular chaperones are key players in proteostasis, the balance between protein synthesis, folding, assembly and degradation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30484157", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 418, "text": "The well-studied Escherichia coli chaperonin GroEL binds non-native substrates and encapsulates them in the cavity thereby sequestering the substrates from unfavorable conditions and allowing the substrates to fold.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25986150", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 941, "text": "The fact that high-affinity co-chaperonin binding impairs chaperonin function has implications for the mechanism of chaperonin-assisted protein folding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10380224", "endSection": "abstract" }, { "offsetInBeginSection": 825, "offsetInEndSection": 991, "text": "Our analysis reveals that both the orchestration of protein folding and circadian rhythms mediated by CCT chaperonin are critical for maintaining heart contractility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28963798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "The eukaryotic cytosolic chaperonin containing TCP-1 (CCT) has an important function in maintaining cellular homoeostasis by assisting the folding of many proteins, including the cytoskeletal components actin and tubulin. Y", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18511909", "endSection": "abstract" }, { "offsetInBeginSection": 980, "offsetInEndSection": 1241, "text": "the functional chaperonin containing CPNA2 could assist the folding of a specific substrate, KASI (\u03b2-ketoacyl-[acyl carrier protein] synthase I), and that the KASI protein level was remarkably reduced due to loss-of-function of CPNA2. Furthermore, the reduction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28961247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Heat shock proteins (HSPs) 60 and 10 are stress-inducible mitochondrial matrix proteins that form a chaperonin complex that is important for mitochondrial protein folding and function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11295228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Eukaryotic prefoldin (PFD) is a heterohexameric chaperone with a jellyfish-like structure whose function is to deliver nonnative target proteins, principally actins and tubulins, to the eukaryotic cytosolic chaperonin for facilitated folding. He", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14634002", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The major heat shock protein, chaperonin 60, has been established to have intercellular signaling activity in addition to its established protein-folding function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15677470", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 474, "text": " injury. Two other heat shock proteins (HSP60 and HSP10) are known to form, within the mitochondria, a chaperonin complex that is important for mitochondrial protein folding and fun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9337202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "BACKGROUND: Chaperonins are important in living systems because they play a role in the folding ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21702926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Chaperonins are large ring assemblies that assist protein folding to the native state by binding nonnative proteins in their central cavities and then, upon binding ATP, release the substrate protein into a now-encapsulated cavity to fold productively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17489689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Chaperonins are protein-folding machinery found in all cellular life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28731469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Chaperonins are macromolecular machines that assist in protein folding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Chaperonins are a subclass of molecular chaperones that assist cellular proteins to fold and assemble into their native shape.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29696145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Chaperonins are universally conserved molecular machines that facilitate the proper -folding of nascent and partially folded polypeptides into their respective three-dimensional structures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22297519", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Chaperonins are large oligomers made up of two superimposed rings, each enclosing a cavity used for the folding of other proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12354605", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "It is now well understood that, although proteins fold spontaneously (in a thermodynamic sense), many nevertheless require the assistance of helpers called molecular chaperones to reach their correct and active folded state in living cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21265753", "endSection": "abstract" } ] }, { "body": "Can FTO promote pancreatic cancer development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34484859" ], "ideal_answer": [ "No, the m6A demethylase FTO suppresses pancreatic cancer tumorigenesis." ], "exact_answer": "no", "type": "yesno", "id": "622629d13a8413c65300007e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "m6A demethylase FTO suppresses pancreatic cancer tumorigenesis by demethylating PJA2 and inhibiting Wnt signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34484859", "endSection": "title" }, { "offsetInBeginSection": 931, "offsetInEndSection": 1185, "text": "Moreover, FTO demethylated the m6A modification of praja ring finger ubiquitin ligase 2 (PJA2), thereby reducing its mRNA decay, suppressing Wnt signaling, and ultimately restraining the proliferation, invasion, and metastasis of pancreatic cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34484859", "endSection": "abstract" } ] }, { "body": "Which disorder is caused by biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33252155" ], "ideal_answer": [ "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB).", "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB)", "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB), which is caused by a protein-coupled receptor-protein interaction." ], "exact_answer": [ "Oguchi disease" ], "type": "factoid", "id": "61f95f9f882a024a1000004e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33252155", "endSection": "abstract" } ] }, { "body": "Which disease is treated with Tebentafusp?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32725406", "http://www.ncbi.nlm.nih.gov/pubmed/34551229", "http://www.ncbi.nlm.nih.gov/pubmed/34885078", "http://www.ncbi.nlm.nih.gov/pubmed/33839690", "http://www.ncbi.nlm.nih.gov/pubmed/32273508", "http://www.ncbi.nlm.nih.gov/pubmed/32816891" ], "ideal_answer": [ "Tebentafusp is used for treatment of Metastatic Uveal Melanoma." ], "exact_answer": [ "Metastatic Uveal Melanoma" ], "type": "factoid", "id": "61f5fb64882a024a1000001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34551229", "endSection": "title" }, { "offsetInBeginSection": 1939, "offsetInEndSection": 2108, "text": "CONCLUSIONS: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34551229", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 318, "text": "If approved, tebentafusp could become the standard of care for metastatic uveal melanoma-but only for those patients with a particular HLA allele.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33839690", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 986, "text": "Recently, a randomized phase III trial reported an overall survival benefit for tebentafusp in patients with untreated metastatic uveal melanoma. The aim of this comprehensive review is to summarize evidence of Gp-100 as a therapeutic target in melanoma, and the preclinical and clinical development of tebentafusp as a novel therapeutic strategy for patients with uveal melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34885078", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1193, "text": "Although UM metastases are less responsive than cutaneous melanoma to chemotherapy or immune checkpoint inhibitors, encouraging results have been reported with partial hepatectomy for solitary metastases, with percutaneous hepatic perfusion with melphalan or with tebentafusp.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32273508", "endSection": "abstract" }, { "offsetInBeginSection": 520, "offsetInEndSection": 943, "text": "Several alternative systemic therapeutic approaches have been or are currently being investigated, including two agents that have been taken into registration-intent clinical trials: tebentafusp, a T cell redirecting agent, and IDE196, an oral protein kinase C inhibitor. Treatment of advanced uveal melanoma remains challenging, however, encouraging results from novel agents offer hope for improvement in the near future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32725406", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 818, "text": "melanoma received tebentafusp. Treatment efficacy, treatment-related adverse events, and biomarker assessments were performed for blood-derived and tumor biopsy samples obtained at baseline and on-treatment.RESULTS: Tebentafusp was generally well-tolerated and active in both patients with metastatic uveal melanoma and pati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32816891", "endSection": "abstract" } ] }, { "body": "Is Lysozyme abundant in human tears?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34431892", "http://www.ncbi.nlm.nih.gov/pubmed/32081946", "http://www.ncbi.nlm.nih.gov/pubmed/32227027", "http://www.ncbi.nlm.nih.gov/pubmed/33964291", "http://www.ncbi.nlm.nih.gov/pubmed/34384745", "http://www.ncbi.nlm.nih.gov/pubmed/31839581" ], "ideal_answer": [ "Yes,\nlysozyme is the most prevalent protein in tear fluid." ], "exact_answer": "yes", "type": "yesno", "id": "621b8dee3a8413c653000042", "snippets": [ { "offsetInBeginSection": 415, "offsetInEndSection": 451, "text": "lysozyme present in the natural tear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33964291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Lysozyme (Lyz) is a naturally occurring enzyme that operates against Gram-positive bacteria and leads to cell death. This antimicrobial enzyme forms the part of the innate defense system of nearly all animals and exists in their somatic discharges such as milk, tears, saliva and urine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34384745", "endSection": "abstract" }, { "offsetInBeginSection": 42, "offsetInEndSection": 55, "text": "tear lysozyme", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431892", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 441, "text": "lysozyme in tears, saliva, sweat, and other body fluids, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31839581", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 264, "text": "In this study we quantify lysozyme, the most prevalent protein in tear fluid, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Lysozyme (LZM) is a natural anti-bacterial protein that is found in the saliva, tears and milk of all mammals including humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32081946", "endSection": "abstract" } ] }, { "body": "What is Neuromedin U (NmU)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27512149", "http://www.ncbi.nlm.nih.gov/pubmed/32010240", "http://www.ncbi.nlm.nih.gov/pubmed/15585845", "http://www.ncbi.nlm.nih.gov/pubmed/12890516", "http://www.ncbi.nlm.nih.gov/pubmed/11027662", "http://www.ncbi.nlm.nih.gov/pubmed/11708803", "http://www.ncbi.nlm.nih.gov/pubmed/17016626", "http://www.ncbi.nlm.nih.gov/pubmed/18948835", "http://www.ncbi.nlm.nih.gov/pubmed/10894543", "http://www.ncbi.nlm.nih.gov/pubmed/32013887", "http://www.ncbi.nlm.nih.gov/pubmed/31492042", "http://www.ncbi.nlm.nih.gov/pubmed/28291683", "http://www.ncbi.nlm.nih.gov/pubmed/32462086", "http://www.ncbi.nlm.nih.gov/pubmed/11853869", "http://www.ncbi.nlm.nih.gov/pubmed/25605682", "http://www.ncbi.nlm.nih.gov/pubmed/19324999", "http://www.ncbi.nlm.nih.gov/pubmed/32888314", "http://www.ncbi.nlm.nih.gov/pubmed/31899262" ], "ideal_answer": [ "Neuromedin U (NmU) is a highly conserved neuropeptide and has multiple physiological and pathophysiological roles detected, ranging from smooth muscle contraction, feeding, energy balance to tumorigenesis, stress responses, and inflammation.", "Neuromedin U (NmU) is a bioactive neuropeptide that is highly distributed in the central nervous system and the gastrointestinal tract. It has a number of physiological and pathophysiological roles, ranging from feeding behavior, energy metabolism, stress responses, circadian rhythmicity and inflammation." ], "type": "summary", "id": "603e4dc71cb411341a00015f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Since the discovery of neuromedin U (NmU) from porcine spinal cord in 1985, this neuropeptide has been subsequently identified in many other species with multiple physiological and pathophysiological roles detected, ranging from smooth muscle contraction, feeding, energy balance to tumorigenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888314", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 469, "text": "NmU is also emerging to play pro-inflammatory roles involving immune cell activation and cytokine release in a neuron-dependent or neuron-independent manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32888314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Neuromedin U (NMU) is a highly conserved neuropeptide that has been implicated in the stress response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31899262", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 172, "text": "Neuromedin U (NMU) is a neuropeptide belonging to the neuromedin family. Recently, significant associations between NMU and several cancers have been reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32013887", "endSection": "abstract" }, { "offsetInBeginSection": 1551, "offsetInEndSection": 1669, "text": " NMU may serve as a novel prognostic biomarker for HCC patients, although further validation is needed in the future. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32013887", "endSection": "abstract" }, { "offsetInBeginSection": 1673, "offsetInEndSection": 1789, "text": "activation of M2 macrophages and a type-2 inflammatory response may involve in the role of NMU in patients with HCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32013887", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 376, "text": "An increasing number of studies have demonstrated that neuromedin U (NMU) plays a pleiotropic role in the pathogenesis of asthma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32010240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Neuromedin U (NMU) is a bioactive neuropeptide, highly distributed in the gastrointestinal tract and the central nervous system. NMU has various physiological functions related to feeding behavior, energy metabolism, stress responses, circadian rhythmicity and inflammation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32462086", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 396, "text": "reports indicate that the central NMU system plays an important role in the reward systems in the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32462086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "OBJECTIVES: Neuromedin U (NmU) is a neuropeptide with anorexigenic activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18948835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Neuromedin U (NmU) is a regulatory peptide found in significant concentrations in both the brain and gut of the rat and is named according to its ability to powerfully contract the uterus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17016626", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 356, "text": "Neuromedin U (NmU) is a neuropeptide known for its uterocontractile effects in rodents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27512149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Neuromedin U (NMU) is a brain-gut peptide, which peripherally stimulates smooth muscle, increases of blood pressure, alters ion transport in the gut, controls local blood flow, and regulates adrenocortical function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11853869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Neuromedin U (NMU) and neuromedin S (NMS) are structurally related neuropeptides that have been reported to modulate energy homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19324999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The neuropeptide neuromedin U (NMU) has been shown to have significant effects on cardiovascular, gastrointestinal and CNS functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12890516", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Neuromedin U (NmU), originally isolated from porcine spinal cord and later from other species, is a novel peptide that potently contracts smooth muscle. N", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15585845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Neuromedin U (NMU) is a neuropeptide known to regulate food intake and energy homeostasis that is widely distributed in the gastrointestinal tract, hypothalamus, and pituitary. A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "OBJECTIVES: Neuromedin U (NmU) is a neuropeptide with anorexigeni", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18948835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10894543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Neuromedin U (NMU) is a brain-gut peptide whose peripheral activities are well-understood but whose central actions have yet to be clarified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11027662", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Neuromedin U (NMU) is a hypothalamic peptide that has been recently found to reduce food intake, but few is known about its other functions in the central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11708803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Neuromedin U (NmU), originally isolated from porcine spinal cord and later from other species, is a novel peptide that potently contracts smooth muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15585845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 582, "text": "BACKGROUND: Neuromedin U (NmU) belongs to the neuromedin family, comprising a series of neuropeptides involved in the gut-brain axis and including neuromedins B and C (bombesin-like), K (neurokinin B), L (neurokinin A or neurotensin), N, S, and U.CONTENT: Although initially isolated from porcine spinal cord on the basis of their ability to induce uterine smooth muscle contraction, these peptides have now been found to be expressed in several different tissues and have been ascribed numerous functions, from appetite regulation and energy balance control to muscle contraction a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25605682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Neuromedin U (NMU), a neuropeptide isolated from porcine spinal cord and named because of its activity as a rat uterus smooth muscle contraction inducer, is emerging as a new player in the tumorigenesis and/or metastasis of many types of cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31492042", "endSection": "abstract" } ] }, { "body": "Is FTY720 FDA approved?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31785606" ], "ideal_answer": [ "Yes, FTY720 was approved by the US Food and Drug Administration (FDA) in 2010." ], "exact_answer": "yes", "type": "yesno", "id": "6052715494d57fd87900000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "FTY720 (Fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31785606", "endSection": "abstract" } ] }, { "body": "Describe SPar-K", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31116370" ], "ideal_answer": [ "SPar-K is a method to search for archetypical chromatin architectures by partitioning a set of genomic regions characterized by chromatin signal profiles around ChIP-seq peaks and other kinds of functional sites. This method efficiently deals with problems of data heterogeneity, limited misalignment of anchor points and unknown orientation of asymmetric patterns.", "SPar-K (Signal Partitioning with K-means) is a method to search for archetypical chromatin architectures by partitioning a set of genomic regions characterized by chromatin signal profiles around ChIP-seq peaks and other kinds of functional sites. This method efficiently deals with problems of data heterogeneity, limited misalignment of anchor points and unknown orientation of asymmetric patterns.", "SPar-K (Signal Partitioning with K-means) is a method to search for archetypical chromatin architectures by partitioning a set of genomic regions characterized by chromatin signal profiles around ChIP-seq peaks and other functional sites." ], "type": "summary", "id": "61f9cc19c9dfcb9c09000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "SPar-K: a method to partition NGS signal data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31116370", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 418, "text": "We present SPar-K (Signal Partitioning with K-means), a method to search for archetypical chromatin architectures by partitioning a set of genomic regions characterized by chromatin signal profiles around ChIP-seq peaks and other kinds of functional sites. This method efficiently deals with problems of data heterogeneity, limited misalignment of anchor points and unknown orientation of asymmetric patterns.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31116370", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of donanemab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34585215", "http://www.ncbi.nlm.nih.gov/pubmed/34489680", "http://www.ncbi.nlm.nih.gov/pubmed/34162295", "http://www.ncbi.nlm.nih.gov/pubmed/34769222", "http://www.ncbi.nlm.nih.gov/pubmed/33720637", "http://www.ncbi.nlm.nih.gov/pubmed/34880449", "http://www.ncbi.nlm.nih.gov/pubmed/34536669", "http://www.ncbi.nlm.nih.gov/pubmed/34198582" ], "ideal_answer": [ "Donanemab is a new monoclonal antibody that uniquely targets A\u03b2(p3-42), a pyroglutamate form of Amyloid-\u03b2 (A\u03b2) exclusively found in plaques." ], "type": "summary", "id": "61f6048e882a024a10000020", "snippets": [ { "offsetInBeginSection": 1022, "offsetInEndSection": 1209, "text": "Considering the recent clinical success of donanemab, which targets A\u03b2\u039d3pE, small molecule-based QC inhibitors may also provide potential therapeutic options for early-stage AD treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34536669", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 693, "text": "Recently, passive immunization of AD patients with Donanemab, an antibody directed against the N-terminus of pyroglutamate A\u03b2, showed beneficial effects in a phase II trial, supporting the concept that N-truncated A\u03b2 is a relevant target for AD therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34489680", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1327, "text": "The late-stage agents with positive clinical or biomarker data include four antibodies that engage A\u03b2 oligomers (aducanumab, lecanemab, gantenerumab, and donanemab) and ALZ-801, an oral agent that fully blocks the formation of A\u03b2 oligomers at the clinical dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34198582", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 319, "text": "Donanemab (LY3002813) is a new monoclonal antibody that uniquely targets A\u03b2(p3-42), a pyroglutamate form of Amyloid-\u03b2 (A\u03b2) exclusively found in plaques.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34162295", "endSection": "abstract" }, { "offsetInBeginSection": 710, "offsetInEndSection": 972, "text": "matically changed with the report that passive immunization with donanemab, an A\u03b2pE3-specific antibody, cleared aymloid plaques and stabilized cognitive deficits in a group of patients with mild AD in a phase II trial. This review summarizes the current knowledg", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34880449", "endSection": "abstract" }, { "offsetInBeginSection": 698, "offsetInEndSection": 936, "text": "tion has dramatically changed with the report that passive immunization with donanemab, an A\u03b2pE3-specific antibody, cleared aymloid plaques and stabilized cognitive deficits in a group of patients with mild AD in a phase II trial. This re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34880449", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 342, "text": "aches targeting pGlu3-A\u03b2 by glutaminyl cyclase (QC) inhibition (Varoglutamstat) or monoclonal antibodies (Donanemab) are currently in clinical development. Here, we ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34769222", "endSection": "abstract" }, { "offsetInBeginSection": 84, "offsetInEndSection": 224, "text": "peptide. Donanemab, an antibody that targets a modified form of deposited A\u03b2, is being investigated for the treatment of early Alzheimer's d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33720637", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 702, "text": "y, passive immunization of AD patients with Donanemab, an antibody directed against the N-terminus of pyroglutamate A\u03b2, showed beneficial effects in a phase II trial, supporting the concept that N-truncated A\u03b2 is a relevant target for AD therapy. There is ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34489680", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 313, "text": "s costly. Donanemab (LY3002813) is a new monoclonal antibody that uniquely targets A\u03b2(p3-42), a pyroglutamate form of Amyloid-\u03b2 (A\u03b2) exclusively found in pl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34162295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: Donanemab (LY3002813) is an IgG1 antibody directed at an N\u2011terminal pyroglutamate of amyloid beta epitope that is present only in brain amylo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Donanemab (LY3002813) is an IgG1 antibody directed at an N\u2011terminal pyroglutamate of amyloid beta epitope that is present only in brain amyl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585215", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 219, "text": "\u03b2) peptide. Donanemab, an antibody that targets a modified form of deposited A\u03b2, is being investigated for the treatment of early Alzheime", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33720637", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 412, "text": "nd is costly. Donanemab (LY3002813) is a new monoclonal antibody that uniquely targets A\u03b2(p3-42), a pyroglutamate form of Amyloid-\u03b2 (A\u03b2) exclusively found in plaques.AREAS COVERED: The phase 2 trial of donanemab in participants with early symptomatic Alzheime", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34162295", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 389, "text": "\u03b2) peptide. Donanemab, an antibody that targets a modified form of deposited A\u03b2, is being investigated for the treatment of early Alzheimer's disease.METHODS: We conducted a phase 2 trial of donanemab in patients with early symptomatic Alzheimer's disease who had tau and amyloid deposition on positron-emiss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33720637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 951, "text": "BACKGROUND: Donanemab (LY3002813) is an IgG1 antibody directed at an N\u2011terminal pyroglutamate of amyloid beta epitope that is present only in brain amyloid plaques.OBJECTIVES: To assess effects of donanemab on brain amyloid plaque load after single and multiple intravenous doses, as well as pharmacokinetics, safety/tolerability, and immunogenicity.DESIGN: Phase 1b, investigator- and patient-blind, randomized, placebo-controlled study.SETTING: Patients recruited at clinical research sites in the United States and Japan.PARTICIPANTS: 61 amyloid plaque-positive patients with mild cognitive impairment due to Alzheimer's disease and mild-to-moderate Alzheimer's disease dementia.INTERVENTION: Six cohorts were dosed with donanemab: single dose 10-, 20- or 40- mg/kg (N = 18), multiple doses of 10-mg/kg every 2 weeks for 24 weeks (N = 10), and 10- or 20-mg/kg every 4 weeks for 72 weeks (N=18) or placebo (N = 15).MEASUREMENTS: Brain amyloid plaque", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585215", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 692, "text": "Recently, passive immunization of AD patients with Donanemab, an antibody directed against the N-terminus of pyroglutamate A\u03b2, showed beneficial effects in a phase II trial, supporting the concept that N-truncated A\u03b2 is a relevant target for AD therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34489680", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 928, "text": "This situation has dramatically changed with the report that passive immunization with donanemab, an A\u03b2pE3-specific antibody, cleared aymloid plaques and stabilized cognitive deficits in a group of patients with mild AD in a phase II trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34880449", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 332, "text": "Approaches targeting pGlu3-A\u03b2 by glutaminyl cyclase (QC) inhibition (Varoglutamstat) or monoclonal antibodies (Donanemab) are currently in clinical development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34769222", "endSection": "abstract" } ] }, { "body": "Is cytokeratin a tumor marker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33321564", "http://www.ncbi.nlm.nih.gov/pubmed/34593462", "http://www.ncbi.nlm.nih.gov/pubmed/34163223", "http://www.ncbi.nlm.nih.gov/pubmed/32577996" ], "ideal_answer": [ "Yes,\ncytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a tumor marker." ], "exact_answer": "yes", "type": "yesno", "id": "621d19cc3a8413c65300004a", "snippets": [ { "offsetInBeginSection": 81, "offsetInEndSection": 239, "text": "cytokeratin fragment antigen\u00a021-1 (CYFRA21-1) in patients with laryngeal squamous cell carcinoma (LSCC) and its correlation with tumorigenesis and progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32577996", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 781, "text": " cytokeratin fragment 19 (AUC=0.6882, p<0.0001) proved best in detecting relapse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34593462", "endSection": "abstract" }, { "offsetInBeginSection": 1134, "offsetInEndSection": 1290, "text": "The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33321564", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 613, "text": "evels of inflammatory and tumor markers, including carbohydrate antigen (CA) 19-9, CA125, carcinoembryonic antigen (CEA), CA153, and cytokeratin 19 fragments (CYFRA21-1), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34163223", "endSection": "abstract" } ] }, { "body": "What are TAMs in cancer therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33568427", "http://www.ncbi.nlm.nih.gov/pubmed/29730267", "http://www.ncbi.nlm.nih.gov/pubmed/34060821", "http://www.ncbi.nlm.nih.gov/pubmed/34006822", "http://www.ncbi.nlm.nih.gov/pubmed/32708142", "http://www.ncbi.nlm.nih.gov/pubmed/28341752", "http://www.ncbi.nlm.nih.gov/pubmed/34276698", "http://www.ncbi.nlm.nih.gov/pubmed/32445205", "http://www.ncbi.nlm.nih.gov/pubmed/25620672", "http://www.ncbi.nlm.nih.gov/pubmed/34469109", "http://www.ncbi.nlm.nih.gov/pubmed/29436395", "http://www.ncbi.nlm.nih.gov/pubmed/34515617", "http://www.ncbi.nlm.nih.gov/pubmed/29691294", "http://www.ncbi.nlm.nih.gov/pubmed/33050070", "http://www.ncbi.nlm.nih.gov/pubmed/31704343", "http://www.ncbi.nlm.nih.gov/pubmed/33881837", "http://www.ncbi.nlm.nih.gov/pubmed/34695762" ], "ideal_answer": [ "TAMs are Tumor Associated Macrophages and are important in Cancer therapy." ], "exact_answer": [ "Tumor Associated Macrophages" ], "type": "factoid", "id": "6222257e3a8413c653000077", "snippets": [ { "offsetInBeginSection": 1041, "offsetInEndSection": 1078, "text": " tumor-associated macrophages (TAMs) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34695762", "endSection": "abstract" }, { "offsetInBeginSection": 599, "offsetInEndSection": 635, "text": "tumour-associated macrophages (TAMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33568427", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 302, "text": " tumor-associated macrophages (TAMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34469109", "endSection": "abstract" }, { "offsetInBeginSection": 739, "offsetInEndSection": 774, "text": "tumor-associated macrophages (TAMs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34515617", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 302, "text": "However, endocrine therapy resistance mechanisms mediated through interactions between breast cancer cells and tumor-associated macrophages (TAMs) are still unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34006822", "endSection": "abstract" }, { "offsetInBeginSection": 358, "offsetInEndSection": 563, "text": "ntional cancer therapy also strengthens cancer-related inflammation by inducing massive tumor cell death that activate surrounding immune-infiltrating cells such as tumor-associated macrophages (TAMs). Mac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34276698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Although M2-like tumor-associated macrophages (TAMs) have been considered as a vital therapeutic target in cancer therapy due to their role in promoting tumor progression and metastasis, very few compounds have been identified to inhibit M2-like polarization of TAMs. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29730267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29436395", "endSection": "abstract" }, { "offsetInBeginSection": 138, "offsetInEndSection": 592, "text": "As CSCs depend on their specific niche, including tumor-associated macrophages (TAM), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer.Experimental Design: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA sequencing, co-immunoprecipitation, chromatin immunoprecipitation, and other assays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29691294", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Tumor-associated macrophages (TAMs) is a promising therapeutic target for cancer immunotherapy, while TAMs targeting therapy using nano-sized drug delivery system (NDDS) is a great challenge.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31704343", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Tumor-associated macrophages (TAMs) play a crucial part in cancer evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34060821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Tumor-associated macrophages (TAMs) of M2 phenotype have mediated the immunosuppression in a tumor microenvironment, facilitating the escape of tumor cells from immunosurveillance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33881837", "endSection": "abstract" }, { "offsetInBeginSection": 399, "offsetInEndSection": 554, "text": "In this review, we outline the importance of tumor-associated macrophages (TAM), a major component of the TME, in the response of tumors to cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28341752", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 415, "text": "In particular, tumor-associated macrophages (TAMs) are the most abundant leucocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33050070", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 368, "text": "These cells, known as tumor-associated macrophages (TAMs), play complex but pivotal roles in the outcome of photodynamic therapy (PDT) of malignant lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25620672", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Tumor-associated macrophages (TAMs) represent the most abundant innate immune cells in tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32708142", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 253, "text": "Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the TME.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32445205", "endSection": "abstract" } ] }, { "body": "What is the relationship between RUNX1T1 and FTO?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25881961", "http://www.ncbi.nlm.nih.gov/pubmed/25412662" ], "ideal_answer": [ "FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. The effect of FTO on adipogenesis appears to be mediated via enhanced expression of the pro-adipogenic short isoform of RUNX1T1." ], "type": "summary", "id": "62260aa13a8413c65300007a", "snippets": [ { "offsetInBeginSection": 655, "offsetInEndSection": 882, "text": "The effect of FTO on adipogenesis appears to be mediated via enhanced expression of the pro-adipogenic short isoform of RUNX1T1, which enhanced adipocyte proliferation, and is increased in FTO-4 MEFs and reduced in FTO-KO MEFs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25881961", "endSection": "abstract" }, { "offsetInBeginSection": 830, "offsetInEndSection": 983, "text": "FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25412662", "endSection": "abstract" } ] }, { "body": "Which java utility has been developed for class hidden markov models?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31250907" ], "ideal_answer": [ "JUCHMME is an open-source software package designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols, and is used for biological sequence analysis and class hidden markov models in Java EE 8 and Java EE 9.", "JUCHMME is an open-source software package designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols.", "JUCHMME is an open-source software package in Java designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols." ], "exact_answer": [ "JUCHMME" ], "type": "factoid", "id": "6200411cc9dfcb9c09000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "JUCHMME: a Java Utility for Class Hidden Markov Models and Extensions for biological sequence analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31250907", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 149, "text": "JUCHMME is an open-source software package designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31250907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "SUMMARY: JUCHMME is an open-source software package designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31250907", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Etesevimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34537363", "http://www.ncbi.nlm.nih.gov/pubmed/34555986", "http://www.ncbi.nlm.nih.gov/pubmed/34006961", "http://www.ncbi.nlm.nih.gov/pubmed/34514598", "http://www.ncbi.nlm.nih.gov/pubmed/33972256", "http://www.ncbi.nlm.nih.gov/pubmed/34374951", "http://www.ncbi.nlm.nih.gov/pubmed/34504497", "http://www.ncbi.nlm.nih.gov/pubmed/34511939", "http://www.ncbi.nlm.nih.gov/pubmed/34433754" ], "ideal_answer": [ "Etesevimab is a neutralizing antibody indicated for treatment of coronavirus disease 2019 (COVID-19) in patients with early mild or moderate disease." ], "type": "summary", "id": "61f5f777882a024a10000018", "snippets": [ { "offsetInBeginSection": 1599, "offsetInEndSection": 1679, "text": "Two antibodies (bamlanivimab and etesevimab) have just been approved by the FDA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34511939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Bamlanivimab and etesevimab are neutralizing antibodies indicated for treatment of coronavirus disease 2019 (COVID-19) in patients with early mild or moderate disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34514598", "endSection": "abstract" }, { "offsetInBeginSection": 502, "offsetInEndSection": 638, "text": "The mAbs used were: Bamlanivimab alone (four patients), Bamlanivimab/Etesevimab (23 patients) and Casirivimab/Imdevimab (five patients).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34537363", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 186, "text": "Bamlanivimab and etesevimab are monoclonal antibodies to SARS-CoV-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34555986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Population Pharmacokinetics and Pharmacodynamics of the Neutralizing Antibodies Bamlanivimab and Etesevimab in Patients With Mild to Moderate COVID-19 Infection", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34514598", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "A Narrative Review of the Clinical Practicalities of Bamlanivimab and Etesevimab Antibody Therapies for SARS-CoV-2", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34374951", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Bamlanivimab and etesevimab are neutralizing antibodies indicated for treatment of coronavirus disease 2019 (COVID-19) in patients with early mild or moderate disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34514598", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 571, "text": "Bamlanivimab and etesevimab are monoclonal antibodies (mAbs) that target the SARS-CoV-2 spike protein and block entry of SARS-CoV-2 in host cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34504497", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 880, "text": "For example, bamlanivimab and etesevimab, which are newly designed monoclonal antibodies against the surface spike protein S1 subunit receptor-binding domain (RBD) of SARS-CoV-2, have a significant effect on reducing the viral load and the hospitalization rate of patients with mild COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34433754", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 368, "text": "l antibodies. Bamlanivimab and etesevimab are monoclonal antibodies to SARS-CoV-2.AREAS COVERED: This evaluation is of the phase 3 BLAZE-1 clinical trial, which was of bamlanivimab plus etesevimab in adult ambulatory participants with a risk factor for, and mild t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34555986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab, in Chinese Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33972256", "endSection": "title" }, { "offsetInBeginSection": 427, "offsetInEndSection": 605, "text": "We have re-engineered six anti-SARS-CoV-2 antibodies using the human p53 tetramerization domain, including three clinical trials antibodies casirivimab, imdevimab and etesevimab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34006961", "endSection": "abstract" } ] }, { "body": "List known pseudokinases.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34496019", "http://www.ncbi.nlm.nih.gov/pubmed/34537014", "http://www.ncbi.nlm.nih.gov/pubmed/32730594", "http://www.ncbi.nlm.nih.gov/pubmed/34567510", "http://www.ncbi.nlm.nih.gov/pubmed/34543009", "http://www.ncbi.nlm.nih.gov/pubmed/32397857", "http://www.ncbi.nlm.nih.gov/pubmed/32687661", "http://www.ncbi.nlm.nih.gov/pubmed/34548332" ], "ideal_answer": [ "TRIB1\nTRIB2\nTRIB3\nMLKL\nULK4\nHER3\nCASK" ], "exact_answer": [ [ "TRIB1" ], [ "TRIB2" ], [ "TRIB3" ], [ "MLKL" ], [ "ULK4" ], [ "HER3" ], [ "CASK" ] ], "type": "list", "id": "621b85993a8413c653000041", "snippets": [ { "offsetInBeginSection": 272, "offsetInEndSection": 290, "text": "TRIB3 pseudokinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32397857", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 770, "text": " mixed-lineage kinase domain-like pseudokinase (MLKL) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32687661", "endSection": "abstract" }, { "offsetInBeginSection": 4, "offsetInEndSection": 22, "text": "pseudokinase Trib1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730594", "endSection": "abstract" }, { "offsetInBeginSection": 1805, "offsetInEndSection": 1822, "text": "ULK4 pseudokinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34537014", "endSection": "abstract" }, { "offsetInBeginSection": 603, "offsetInEndSection": 620, "text": "JAK1 pseudokinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34496019", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 325, "text": "CASK, led to the classification as a pseudokinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34543009", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 260, "text": "HER3 is a unique pseudokinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548332", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1022, "text": "tribbles pseudokinase 2 (TRIB2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34567510", "endSection": "abstract" } ] }, { "body": "Where is the body would the Peyer's patches be found", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11979138", "http://www.ncbi.nlm.nih.gov/pubmed/8674142", "http://www.ncbi.nlm.nih.gov/pubmed/2342879", "http://www.ncbi.nlm.nih.gov/pubmed/28847272", "http://www.ncbi.nlm.nih.gov/pubmed/3500086", "http://www.ncbi.nlm.nih.gov/pubmed/31970486", "http://www.ncbi.nlm.nih.gov/pubmed/31856298", "http://www.ncbi.nlm.nih.gov/pubmed/848258", "http://www.ncbi.nlm.nih.gov/pubmed/19874224", "http://www.ncbi.nlm.nih.gov/pubmed/3029559", "http://www.ncbi.nlm.nih.gov/pubmed/21439318", "http://www.ncbi.nlm.nih.gov/pubmed/29395860", "http://www.ncbi.nlm.nih.gov/pubmed/12206832", "http://www.ncbi.nlm.nih.gov/pubmed/1905075", "http://www.ncbi.nlm.nih.gov/pubmed/1548786", "http://www.ncbi.nlm.nih.gov/pubmed/30298433", "http://www.ncbi.nlm.nih.gov/pubmed/31734952", "http://www.ncbi.nlm.nih.gov/pubmed/23135279", "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "http://www.ncbi.nlm.nih.gov/pubmed/30021891", "http://www.ncbi.nlm.nih.gov/pubmed/6743144", "http://www.ncbi.nlm.nih.gov/pubmed/21461871" ], "ideal_answer": [ "Peyer's patches (PPs) play a major role in intestinal mucosal immunity and are located in the gut." ], "exact_answer": [ "gut", "abdomen", "the small intestine", "intestinal mucosal" ], "type": "factoid", "id": "601eb3b61cb411341a000057", "snippets": [ { "offsetInBeginSection": 20, "offsetInEndSection": 90, "text": "Peyer's patches (PPs) play a major role in intestinal mucosal immunity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31734952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "The small intestine hosts specialized lymphoid structures, the Peyer's patches, that face the gut lumen and are overlaid with unique epithelial cells, called microfold (M) cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31856298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "In the Peyer's patches of the small intestine, specialized epithelial cells, the membranous (M) cells, sample antigenic matter from the gut lumen and bring it into contact with cells of the immune system, which are then capable of initiating specific immune reactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31970486", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 648, "text": "A strong clustering of lymphoid cells originating from either twin was seen in the ileal Peyer's patches (IPPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12206832", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 414, "text": "he gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's patches and elsewhere, which together have profound effects on local and systemic inflammation. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30298433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "During routine lower gastrointestinal endoscopy of children for suspected chronic inflammatory bowel disease, it is possible to visualize lymphoid follicles (Peyer's patches) in the last few centimeters of the terminal ileum. Bi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3500086", "endSection": "abstract" }, { "offsetInBeginSection": 681, "offsetInEndSection": 931, "text": "ls responsible for local pIg production are initially stimulated in lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to exocrine tissues all over the body. Mucous mem", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8674142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "During the course of their recirculation through the body, blood-borne lymphocytes specifically adhere to high endothelial venules (HEV) within secondary lymphoid organs such as peripheral lymph nodes (PN) and gut-associated Peyer's patches (PP). This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3029559", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 673, "text": "this respect, Peyer's patches (PP), represent one of the most important immunological site of the body and the major component of the gut -associated lymphoid tissue. The a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19874224", "endSection": "abstract" }, { "offsetInBeginSection": 656, "offsetInEndSection": 980, "text": "en-stimulated B and T lymphocytes are distributed from Peyer's patches and other gut-associated lymphoid tissue to exocrine glandular sites all over the body; this is the basis for local generation of SIgA antibodies with an enormous selection of specificities required for protection of the extensive mucosal surfaces. Regu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2342879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Peyer's patch have been extensively studied as a major inductive site for mucosal immunity within the small intestine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439318", "endSection": "abstract" }, { "offsetInBeginSection": 734, "offsetInEndSection": 918, "text": "nistration. The Peyer's patches have been considered an important structure of the gut associate lymphoid tissue (GALT) for the initiation of the immune response towards particulate or", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28847272", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 443, "text": "Peyer patches are the major entrance of Salmonella infection and antigen transportation in intestine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23135279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "The early replication of certain prion strains within Peyer's patches in the small intestine is essential for the efficient spread of disease to the brain after oral exposure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30021891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Distribution of Peyer's patches in the distal ileum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11979138", "endSection": "title" }, { "offsetInBeginSection": 288, "offsetInEndSection": 640, "text": "The position of the Peyer's patches is unusual in that the first three Peyer's patches are on the right side of the small intestine whereas the penultimate and ultimate Peyer's patches are large, contain many lymphoid follicles and are in an anti-mesenteric position in the small intestine and sometimes in the large intestine (ultimate Peyer's patch).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6743144", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 296, "text": "Peyer's patches in the small intestine are prominent, ranging from four to 13, and increase in size (surface area) with age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1548786", "endSection": "abstract" }, { "offsetInBeginSection": 1172, "offsetInEndSection": 1409, "text": "The jejunal Peyer's patches are devoid of CAP, persist in the adult animal, contain M cells with clusters of B cells in the follicle-associated epithelium, and have many CD4+ lymphocytes in the follicles and in the interfollicular areas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1905075", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 852, "text": "They were distributed in the whole small intestine and there were four distinct types of Peyer's patches: nodular, faviform, cup-shaped, and cystic form Peyer's patches.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21461871", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Oligoclonal Peyer's patch follicles in the terminal small intestine of cattle.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12206832", "endSection": "title" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1121, "text": "In addition, the distribution density of Peyer's patches in ileum was the maximum, then was jejunum and duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21461871", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 786, "text": "c acid, and transilluminated. Peyer's patches were counted, and the length, breadth, and distance from the ileocecal valve were recorded.RESULTS: Patches were most numerous in the terminal 10-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11979138", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 713, "text": "Located in the small intestine, Peyer's patches (PP) are primary antigen sampling and mucosal immune response inductive sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29395860", "endSection": "abstract" }, { "offsetInBeginSection": 498, "offsetInEndSection": 667, "text": "In this respect, Peyer's patches (PP), represent one of the most important immunological site of the body and the major component of the gut -associated lymphoid tissue.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19874224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "[Number and localization of Peyer's patches in the small intestine of the rabbit (Oryctolagus cuniculus)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/848258", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "In the rabbit intestine Peyer's patches can easily be distinguished.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/848258", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Peyer's patches are gut-associated lymphoid tissue located throughout the intestinal wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 329, "text": "Peyer's patches consist of highly organized ovoid-shaped follicles, classified as non-encapsulated lymphatic tissues, populated with B cells, T cells, macrophages, and dendritic cells and function as an organism's intestinal surveillance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1031, "text": "Rats had a significantly reduced number of Peyer's patches in the duodenum in comparison to either the jejunum or ileum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "endSection": "abstract" }, { "offsetInBeginSection": 1473, "offsetInEndSection": 1616, "text": "In summary, the gene expression pattern of Peyer's patches is influenced by intestinal location and may contribute to its role in that segment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 431, "text": "Limited work compares the gene profiles of Peyer's patches derived from different intestinal regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 910, "text": "Using samples obtained from additional subjects (n\u2009=\u200910), we validated the novel gene expression patterns in Peyer's patches obtained from the three regions of the small intestine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 614, "text": "In the current study, we first performed whole transcriptome analysis using RNAseq to compare duodenal and ileal Peyer's patches obtained from the small intestine of Long Evans rats.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236653", "endSection": "abstract" } ] }, { "body": "Is tofacitinib a JAK inhibitor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31721311" ], "ideal_answer": [ "Yes, tofacitinib is a small JAK inhibitor." ], "exact_answer": "yes", "type": "yesno", "id": "602596691cb411341a0000ad", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31721311", "endSection": "title" }, { "offsetInBeginSection": 195, "offsetInEndSection": 342, "text": "Tofacitinib, a small JAK inhibitor, is approved for the treatment of RA and has demonstrated good efficacy in psoriasis phase III clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31721311", "endSection": "abstract" } ] }, { "body": "Describe the GenomeAsia 100K Project", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31802016" ], "ideal_answer": [ "The GenomeAsia 100K Project (GenomeAsia100K Project) aims to identify and catalogue genetic variation, population structure, disease associations and founder effects in populations across Asia and worldwide. It includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia, as well as a population-wide association dataset.", "The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world's population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. The pilot phase of the GenomeAsia 100K Project includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia." ], "type": "summary", "id": "61f86f58882a024a10000046", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "The GenomeAsia 100K Project enables genetic discoveries across Asia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31802016", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 790, "text": "The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world's population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. Here we describe the pilot phase of the GenomeAsia 100K Project. This includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia. We catalogue genetic variation, population structure, disease associations and founder effects. We also explore the use of this dataset in imputation, to facilitate genetic studies in populations across Asia and worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31802016", "endSection": "abstract" } ] }, { "body": "Which disease is treated with Risdiplam?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33098622", "http://www.ncbi.nlm.nih.gov/pubmed/33626251", "http://www.ncbi.nlm.nih.gov/pubmed/34888619", "http://www.ncbi.nlm.nih.gov/pubmed/34745484", "http://www.ncbi.nlm.nih.gov/pubmed/33231373", "http://www.ncbi.nlm.nih.gov/pubmed/33044711", "http://www.ncbi.nlm.nih.gov/pubmed/34183144", "http://www.ncbi.nlm.nih.gov/pubmed/33919699", "http://www.ncbi.nlm.nih.gov/pubmed/34287987", "http://www.ncbi.nlm.nih.gov/pubmed/34141064", "http://www.ncbi.nlm.nih.gov/pubmed/30302786", "http://www.ncbi.nlm.nih.gov/pubmed/34368854", "http://www.ncbi.nlm.nih.gov/pubmed/34347881", "http://www.ncbi.nlm.nih.gov/pubmed/33130193", "http://www.ncbi.nlm.nih.gov/pubmed/34283224", "http://www.ncbi.nlm.nih.gov/pubmed/30044619", "http://www.ncbi.nlm.nih.gov/pubmed/33458725", "http://www.ncbi.nlm.nih.gov/pubmed/33283185" ], "ideal_answer": [ "Risdiplam is approved for spinal muscular atrophy." ], "exact_answer": [ "spinal muscular atrophy" ], "type": "factoid", "id": "61f60735882a024a10000022", "snippets": [ { "offsetInBeginSection": 1511, "offsetInEndSection": 1750, "text": "Furthermore, drug therapies including injectables such as onasemnogene abeparvovec-xioi (ZOLGENSMA\u00ae), nusinersen (SPINRAZA\u00ae), and an oral-solution, risdiplam (EVRYSDI\u2122), are medications that have been FDA-approved for the treatment of SMA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "The phenotype of spinal muscular atrophy (SMA) has been changing with the recent availability of three FDA-approved treatments: intrathecal nusinersen, intravenous onasemnogene abeparvovec-xioi, and enteral risdiplam. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33098622", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 479, "text": "The United States' Food and Drug Administration's (FDA) approval of nusinersen, onasemnogene abeparvovec, and risdiplam for SMA has challenged existing treatment paradigms with multiple treatment options, a new natural history of the disease, and an emerging understanding of the importance of early and pre-symptomatic treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34183144", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 423, "text": "The discovery of small molecule splicing modifiers and the development of risdiplam for the treatment of spinal muscular atrophy (SMA) have firmly established proof of concept for this exciting new platform and transformed a scientific curiosity into a viable technology to target disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34141064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Risdiplam (Evrysdi\u2122) is an orally administered, survival motor neuron 2 (SMN2)-directed RNA splicing modifier being developed by Roche, PTC Therapeutics Inc and the SMA Foundation for the treatment of the spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33044711", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1031, "text": "SION: Combination therapy with onasemnogene and risdiplam in patients with SMA appears to be well-tolerated. Furth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34287987", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1087, "text": "Risdiplam is currently the only orally administered drug approved by the FDA for the treatment of SMA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34745484", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 561, "text": "Risdiplam is the first and only oral medication to be approved to treat SMA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34745484", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 417, "text": "Risdiplam was approved recently for the treatment of patients with SMA, aged\u00a0\u2265\u00a02\u00a0months in the United States, and is currently under Health Authority review in the EU.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231373", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "OBJECTIVE: Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI\u00ae), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231373", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 422, "text": "The discovery of small molecule splicing modifiers and the development of risdiplam for the treatment of spinal muscular atrophy (SMA) have firmly established proof of concept for this exciting new platform and transformed a scientific curiosity into a viable technology to target disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34141064", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Risdiplam is the first approved small-molecule splicing modulator for the treatment of spinal muscular atrophy (SMA)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34283224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Risdiplam (Evrysdi) improves motor neuron function in patients with spinal muscular atrophy (SMA) and has been approved for the treatment of patients \u22652\u00a0months old. Ri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34347881", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 764, "text": " small-molecule splicing modifier, risdiplam, was also approved for the treatment of SMA, highlighting small molecules as important warheads in the arsenal for regulating RNA splicing. The cellular ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33919699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Risdiplam (Evrysdi\u2122) is an orally administered, survival motor neuron 2 (SMN2)-directed RNA splicing modifier being developed by Roche, PTC Therapeutics Inc and the SMA Foundation for the treatment of the spinal muscular atrophy. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33044711", "endSection": "abstract" }, { "offsetInBeginSection": 565, "offsetInEndSection": 687, "text": "ext. Very recently, an orally deliverable small molecule, risdiplam (Evrysdi\u2122), became the third approved therapy for SMA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33283185", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 424, "text": "i\u2122 (risdiplam), recently approved for the treatment of SMA, and related compounds promote exon 7 inclusion to generate full-length SMN2 mRNA and increase SMN protein levels. SMN\u03947 ty", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34368854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "AIMS: Risdiplam (RG7916, RO7034067) is an orally administered, centrally and peripherally distributed, survival of motor neuron 2 (SMN2) mRNA splicing modifier for the treatment of spinal muscular atrophy (SMA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30302786", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 489, "text": " United States' Food and Drug Administration's (FDA) approval of nusinersen, onasemnogene abeparvovec, and risdiplam for SMA has challenged existing treatment paradigms with multiple treatment options, a new natural history of the disease, and an emerging understanding of the importance of early and pre-symptomatic treatment. The profo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34183144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "The phenotype of spinal muscular atrophy (SMA) has been changing with the recent availability of three FDA-approved treatments: intrathecal nusinersen, intravenous onasemnogene abeparvovec-xioi, and enteral risdiplam. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33098622", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 306, "text": "ently, the primary therapeutic strategy for SMA is to increase the level of SMN via correcting SMN2 splicing (nusinersen and risdiplam). How", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34888619", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 424, "text": "he discovery of small molecule splicing modifiers and the development of risdiplam for the treatment of spinal muscular atrophy (SMA) have firmly established proof of concept for this exciting new platform and transformed a scientific curiosity into a viable technology to target disease. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34141064", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1789, "text": "s including injectables such as onasemnogene abeparvovec-xioi (ZOLGENSMA\u00ae), nusinersen (SPINRAZA\u00ae), and an oral-solution, risdiplam (EVRYSDI\u2122), are medications that have been FDA-approved for the treatment of SMA. This review discusses the current and ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130193", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Risdiplam for the Use of Spinal Muscular Atrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34745484", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Risdiplam in Type 1 Spinal Muscular Atrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33626251", "endSection": "title" }, { "offsetInBeginSection": 1373, "offsetInEndSection": 1567, "text": " These studies indicate that drugs such as risdiplam will be optimally therapeutic when given as early as possible after diagnosis and potentially will be required for the life of an SMA patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34368854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "AIMS: Risdiplam (RG7916, RO7034067) is an orally administered, centrally and peripherally distributed, survival of motor neuron 2 (SMN2) mRNA splicing modifier for the treatment of spinal muscular atrophy ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30302786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 ( SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30044619", "endSection": "title" }, { "offsetInBeginSection": 239, "offsetInEndSection": 544, "text": "n monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged\u00a0\u2265\u00a02\u00a0months in the United States, and is currently under Health Authority review in the EU.METHODS: Subjects included patients with SMA aged 2\u00a0months-60\u00a0years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231373", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1509, "text": "Additionally, we explore the recently FDA-approved small molecule regulator of RNA splicing, risdiplam, for treatment of spinal muscular atrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33458725", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 632, "text": "In August 2020, Evrysdi\u2122 (risdiplam) received its first approval in the USA for the treatment of spinal muscular atrophy in patients 2\u00a0months of age and older.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33044711", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "OBJECTIVE: Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI\u00ae), a survival of motor neuron 2 splicing modifier associated with retinal toxicity ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231373", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 415, "text": "Evrysdi\u2122 (risdiplam), recently approved for the treatment of SMA, and related compounds promote exon 7 inclusion to generate full-length SMN2 mRNA and increase SMN protein levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34368854", "endSection": "abstract" } ] }, { "body": "What is protein palmitoylation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31812495", "http://www.ncbi.nlm.nih.gov/pubmed/32003970", "http://www.ncbi.nlm.nih.gov/pubmed/31935590", "http://www.ncbi.nlm.nih.gov/pubmed/29189096" ], "ideal_answer": [ "Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16\u2011carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization." ], "type": "summary", "id": "604919411cb411341a00016c", "snippets": [ { "offsetInBeginSection": 336, "offsetInEndSection": 385, "text": "post-translational modification by palmitoylation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29189096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16\u2011carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31812495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Palmitoylation (S-acylation) is the reversible conjugation of a fatty acid (usually C16 palmitate) to intracellular cysteine residues of proteins via a thioester linkage. Palmitoylation anchors intracellular regions of proteins to membranes because the palmitoylated cysteine is recruited to the lipid bilayer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31935590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Protein S-palmitoylation is an important post-translational modification (PTM) in blood stages of the malaria parasite, Plasmodium falciparum. S-palmitoylation refers to reversible covalent modification of cysteine residues of proteins by saturated fatty acids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32003970", "endSection": "abstract" } ] }, { "body": "\u0391re plants from the genus Strychnos the original source of curare?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15302523", "http://www.ncbi.nlm.nih.gov/pubmed/23172095", "http://www.ncbi.nlm.nih.gov/pubmed/1501489", "http://www.ncbi.nlm.nih.gov/pubmed/2179633" ], "ideal_answer": [ "Species of plants from the genus Strychnos are the source of curare." ], "exact_answer": "yes", "type": "yesno", "id": "60292dc61cb411341a000110", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 569, "text": "Poisons are widespread in plants and animals and humankind has often tried to turn them to its own advantage. Owing to their poisonous properties, some species of Strychnos genus have been employed mainly in hunting and fishing, as an adjunct to weapons used not only in the search of food and clothes, but also for preventing depredation by wild animals. They have been employed for martial and criminal purposes and also as a means of determining guilt or innocence. By their nature, poisons such as strychnine and curare affect the functioning of the victim's body; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15302523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The ethnobotanical uses of South American species of Strychnos L. (Loganiaceae) are reviewed, with the exception of their major r\u00f4le in the preparation of curare, which will be dealt with in detail elsewhere.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2179633", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 452, "text": "VELOPMENT: Curare is prepared by boiling the roots, bark and stalks of different plants belonging to the Loganiaceae (Strychnos) and Menispermaceae families (Chondrodendron, Curarea and Abuta). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23172095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "The history to about 1850 of the muscle-relaxant poison curare is discussed, especially the developments leading to the botanical identification of the plants that yield the alkaloidal active principles: Loganiaceae (Strychnos species) and Menispermaceae (Abuta, Chondrodendron, and Curarea species).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1501489", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 424, "text": "or centuries. The study reviews the historical and ethnographic aspects of the use of curares and timb\u00f3s in the Amazonian region.DEVELOPMENT: Curare is prepared by boiling the roots, bark and stalks of different plants belonging to the Loganiaceae (Strychnos) and Menispermaceae families (Chondrod", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23172095", "endSection": "abstract" } ] }, { "body": "When was galcanezumab approved by FDA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30550780" ], "ideal_answer": [ "Galcanezumab was approved by the FDA in September 2018." ], "exact_answer": [ "September 2018" ], "type": "factoid", "id": "6028fad21cb411341a000101", "snippets": [ { "offsetInBeginSection": 323, "offsetInEndSection": 448, "text": "Two antibodies, fremanezumab and galcanezumab, directed towards the CGRP ligand, were approved by the FDA in September 2018. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550780", "endSection": "abstract" } ] }, { "body": "Are variants in FHF2 (also known as FGF13) associated with encephalopathy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33245860" ], "ideal_answer": [ "Yes. FHF2 (also known as FGF13) variants are a cause of infantile-onset developmental and epileptic encephalopathy." ], "exact_answer": "yes", "type": "yesno", "id": "61f9605f882a024a1000004f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33245860", "endSection": "title" }, { "offsetInBeginSection": 390, "offsetInEndSection": 1418, "text": "Whole-exome sequencing identified hemi- and heterozygous variants in the N-terminal domain of the A isoform of FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Our findings demonstrate that FHF2 variants are a cause of infantile-onset developmental and epileptic encephalopathy and underline the critical role of the FHF2A isoform in regulating Nav channel function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33245860", "endSection": "abstract" } ] }, { "body": "Tofersen has been developed for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "http://www.ncbi.nlm.nih.gov/pubmed/34704267" ], "ideal_answer": [ "Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis is being studied for the treatment of amyotrophic lateral sclerosis due to SOD1 mutations." ], "exact_answer": [ "amyotrophic lateral sclerosis" ], "type": "factoid", "id": "602356b81cb411341a000099", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 416, "text": "BACKGROUND: Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations.METHODS: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS due to SOD1 mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "endSection": "abstract" }, { "offsetInBeginSection": 1797, "offsetInEndSection": 1981, "text": "CONCLUSIONS: In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 325, "text": "Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations.METHODS: We conducted a ph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 285, "text": "nthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to S", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 499, "text": "ently, the results of a phase I/II study using the antisense oligonucleotides Tofersen to treat familial amyotrophic lateral sclerosis with superoxide dismutase 1 mutation have been reported. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34704267", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 287, "text": " synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 496, "text": "Recently, the results of a phase I/II study using the antisense oligonucleotides Tofersen to treat familial amyotrophic lateral sclerosis with superoxide dismutase 1 mutation have been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34704267", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 395, "text": " mutations.METHODS: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS du", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 394, "text": " synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations.METHODS: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640130", "endSection": "abstract" } ] }, { "body": "What is the cause of lactose intolerance?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32048961", "http://www.ncbi.nlm.nih.gov/pubmed/31802224", "http://www.ncbi.nlm.nih.gov/pubmed/32443748", "http://www.ncbi.nlm.nih.gov/pubmed/30617948", "http://www.ncbi.nlm.nih.gov/pubmed/31904838" ], "ideal_answer": [ "Lactose intolerance is a common condition caused by lactase deficiency and may result in symptoms of lactose malabsorption (bloating, flatulence, abdominal discomfort, and change in bowel habits).\nFour clinical subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital lactase deficiency, adult-type hypolactasia and secondary lactase intolerance." ], "exact_answer": [ "Lactase deficiency" ], "type": "factoid", "id": "606b2b1994d57fd87900005c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Lactose intolerance is a common condition caused by lactase deficiency and may result in symptoms of lactose malabsorption (bloating, flatulence, abdominal discomfort, and change in bowel habits). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30617948", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 259, "text": " Adult lactose intolerance (ALI) significantly alters calcium intake and absorption, and thus may promote osteoporosis. ALI is a recessive condition with a geographical north-south gradient characterised by decreased levels of intestinal lactase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31802224", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 500, "text": "Considerations include recognizing that a substantial proportion of the world's adult population (65%-70%) exhibits lactase nonpersistence, a reduced ability to metabolize lactose to glucose and galactose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31904838", "endSection": "abstract" }, { "offsetInBeginSection": 755, "offsetInEndSection": 961, "text": " Four clinical subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital lactase deficiency, adult-type hypolactasia and secondary lactase intolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32048961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 443, "text": "Lactose intolerance (LI) is characterized by the presence of primarily gastrointestinal clinical signs resulting from colonic fermentation of lactose, the absorption of which is impaired due to a deficiency in the lactase enzyme. These clinical signs can be modified by several factors, including lactose dose, residual lactase expression, concurrent ingestion of other dietary components, gut-transit time, and enteric microbiome composition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32443748", "endSection": "abstract" } ] }, { "body": "What is Etizolam?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30546611", "http://www.ncbi.nlm.nih.gov/pubmed/33031544", "http://www.ncbi.nlm.nih.gov/pubmed/32243020", "http://www.ncbi.nlm.nih.gov/pubmed/25187742", "http://www.ncbi.nlm.nih.gov/pubmed/17666930", "http://www.ncbi.nlm.nih.gov/pubmed/11944589", "http://www.ncbi.nlm.nih.gov/pubmed/33329156", "http://www.ncbi.nlm.nih.gov/pubmed/31153990", "http://www.ncbi.nlm.nih.gov/pubmed/2692969", "http://www.ncbi.nlm.nih.gov/pubmed/20110024", "http://www.ncbi.nlm.nih.gov/pubmed/33169539", "http://www.ncbi.nlm.nih.gov/pubmed/33236683", "http://www.ncbi.nlm.nih.gov/pubmed/25538342" ], "ideal_answer": [ "Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India as an anxiolytic drug with a pharmacologic profile similar to that of the classic benzodiazepines. Neurochemical research suggests that etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type A receptors associated with anxiety (ie, alpha1, beta2, gamma2).", "Etizolam is a thienodiazepine derivative, with high affinity for the benzodiazepine site of GABAA receptors." ], "type": "summary", "id": "60575f5a94d57fd87900002a", "snippets": [ { "offsetInBeginSection": 8, "offsetInEndSection": 242, "text": "Etizolam is a thienodiazepine derivative, with high affinity for the benzodiazepine site of GABAA receptors. It is often referred to as a new (or novel) psychoactive substance, a 'designer' benzodiazepine or a 'street benzodiazepine'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32243020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Etizolam is a novel psychoactive substance and novel benzodiazepine of the thienotriazolodiazepine class that has recently seen an increasing trend in use worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33031544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33169539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Etizolam is a drug from the thienotriazoldiazepine class, widely prescribed as anxiolytic due to its apparently secure toxicological profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31153990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The prevalence of benzodiazepine consumption in Japan is one of the highest worldwide. Etizolam is the most abused drug of the benzodiazepine class.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25187742", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 302, "text": "Etizolam is an anxiolytic drug with a pharmacologic profile similar to that of the classic benzodiazepines. Neurochemical research suggests that etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type A receptors associated with anxiety (ie, alpha1, beta2, gamma2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Etizolam is a novel psychoactive substance and novel benzodiazepine of the thienotriazolodiazepine class that has recently seen an increasing trend in use worldwide. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33031544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "ISSUES: Etizolam is a thienodiazepine derivative, with high affinity for the benzodiazepine site of GABAA receptors. It is often referred ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32243020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Etizolam is a drug from the thienotriazoldiazepine class, widely prescribed as anxiolytic due to its apparently secure toxicological profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31153990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India but has recently appeared as a nonapproved product on the illicit drug market in Europe and North America. Et", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33169539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236683", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 244, "text": "r the years. Etizolam is a designer benzodiazepine (BZD) that has raised concern because of its growing non-medical use, liability to tolerance and dependence, and related", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33329156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Etizolam is a novel psychoactive substance and novel benzodiazepine of the thienotriazolodiazepine class that has recently seen an increasing trend in use worldwide. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33031544", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Etizolam is a drug from the thienotriazoldiazepine class, widely prescribed as anxiolytic due to its apparently secure toxicological profile. N", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31153990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25538342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "ISSUES: Etizolam is a thienodiazepine derivative, with high affinity for the benzodiazepine site of GABAA rec", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32243020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND: Etizolam is an anxiolytic drug with a pharmacologic profile similar to that of the classic benzod", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Etizolam (ETZ) is an antidepressive thienodiazepine drug that is used worldwide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17666930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "BACKGROUND: Etizolam is an anxiolytic drug with a pharmacologic profile similar to that of the classic benz", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20110024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33236683", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 133, "text": "Etizolam is a benzodiazepine-based anti-anxiety agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30546611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "ISSUES: Etizolam is a thienodiazepine derivative, with high affinity for the benzodiazepine site of GABAA re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32243020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India but has recently appeared as a nonapproved product on the illicit drug market in Europe and North America.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33169539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Etizolam in the treatment of generalized anxiety disorder associated with depressive symptoms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2692969", "endSection": "title" }, { "offsetInBeginSection": 86, "offsetInEndSection": 251, "text": "Etizolam is a designer benzodiazepine (BZD) that has raised concern because of its growing non-medical use, liability to tolerance and dependence, and related harms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33329156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25538342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Etizolam, an anti-anxiety agent which is an antagonist of platelet-activating factor receptors, was administered to patients with chronic subdural hematoma (CSH) after hematoma removal to assess the effectiveness for preventing recurrence compared with control patients not given the drug after surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11944589", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Etizolam, an anti-anxiety agent, attenuates recurrence of chronic subdural hematoma--evaluation by computed tomography.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11944589", "endSection": "title" } ] }, { "body": "Is AZD9668 a VEGF mRNA drug?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22197578" ], "ideal_answer": [ "AZD9668 is a reversible and selective inhibitor of neutrophil elastase." ], "exact_answer": "no", "type": "yesno", "id": "602c26171cb411341a000122", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197578", "endSection": "title" }, { "offsetInBeginSection": 100, "offsetInEndSection": 223, "text": "AZD9668 is a reversible and selective inhibitor of NE, well tolerated at doses of 60 mg bid during Phase I/IIa development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22197578", "endSection": "abstract" } ] }, { "body": "What is caused by de novo VPS4A mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33186545" ], "ideal_answer": [ "De novo VPS4A mutations cause multisystem disease with abnormal neurodevelopment. VPS4A normal function is required for multiple human developmental and cellular processes.", "De-novo VPS4A mutations cause multisystem disease with abnormal neurodevelopment, including dyskinesias, dyslipidemia, and dysplastic skin and cartilaginous neoplasia, as well as an inability to control intracranial temperature." ], "type": "summary", "id": "61f9718f882a024a10000050", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186545", "endSection": "title" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1312, "text": "We thus characterize a distinct multisystem disorder caused by mutations affecting VPS4A and demonstrate that its normal function is required for multiple human developmental and cellular processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186545", "endSection": "abstract" } ] }, { "body": "What is the use of pegcetacoplan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34147650", "http://www.ncbi.nlm.nih.gov/pubmed/31474439", "http://www.ncbi.nlm.nih.gov/pubmed/33675755", "http://www.ncbi.nlm.nih.gov/pubmed/34482398", "http://www.ncbi.nlm.nih.gov/pubmed/33711380", "http://www.ncbi.nlm.nih.gov/pubmed/33464651", "http://www.ncbi.nlm.nih.gov/pubmed/34342834", "http://www.ncbi.nlm.nih.gov/pubmed/33730455", "http://www.ncbi.nlm.nih.gov/pubmed/34445916" ], "ideal_answer": [ "Pegcetacoplan is promising for paroxysmal nocturnal haemoglobinuria and Geographic Atrophy." ], "exact_answer": [ [ "Geographic Atrophy" ], [ "paroxysmal nocturnal haemoglobinuria" ] ], "type": "list", "id": "61f5f377882a024a10000016", "snippets": [ { "offsetInBeginSection": 414, "offsetInEndSection": 562, "text": "Addressing some of the unmet needs, a long-acting C5 inhibitor, ravulizumab, and a C3 inhibitor, pegcetacoplan have been also now approved with PNH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34482398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The FDA approval of pegcetacoplan (Empaveli), a PEGylated compstatin-based C3 therapeutic, as a new treatment for paroxysmal nocturnal hemoglobinuria (PNH) marks a milestone in the history of complement drug discovery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34147650", "endSection": "abstract" }, { "offsetInBeginSection": 1530, "offsetInEndSection": 1639, "text": "Pegcetacoplan treatment significantly controlled GA progression even after accounting for these risk factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33675755", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33730455", "endSection": "title" }, { "offsetInBeginSection": 1948, "offsetInEndSection": 2187, "text": "CONCLUSIONS: Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33730455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31474439", "endSection": "title" }, { "offsetInBeginSection": 2137, "offsetInEndSection": 2287, "text": "CONCLUSIONS: Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31474439", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 708, "text": "Pegcetacoplan is the first C3-targeted paroxysmal nocturnal haemoglobinuria (PNH) therapy to be approved (in May 2021) in the USA, where it is indicated for the treatment of adults with PNH, including those switching from C5 inhibitor therapy with eculizumab and ravulizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34342834", "endSection": "abstract" }, { "offsetInBeginSection": 1717, "offsetInEndSection": 2001, "text": "ONCLUSIONS: Results suggest that among patients previously treated with eculizumab, clinical, hematological, and quality of life endpoints were better for patients who received the C3 complement inhibitor pegcetacoplan vs. patients who received ravulizumab, a C5 complement inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34445916", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 382, "text": "Pegcetacoplan (APL-2), a PEGylated C3 inhibitor, has the potential to provide more complete hemolysis control in patients with PNH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33464651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "OBJECTIVE: In the absence of a head-to-head study, we assessed the comparative effectiveness of pegcetacoplan, a targeted C3 complement inhibitor, vs. ravulizumab, a C5 complement inhibitor, among patients with paroxysmal nocturnal hemoglobinuria (PNH) previously treated with eculizumab using matching-adjusted indirect comparison methodology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34445916", "endSection": "abstract" }, { "offsetInBeginSection": 805, "offsetInEndSection": 1018, "text": "Beyond PNH, complement inhibition has also shown efficacy and safety in cold agglutinin disease (CAD), primarily with the C1s inhibitor of the classical complement pathway, sutimlimab, but also with pegcetacoplan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34482398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "The FDA approval of pegcetacoplan (Empaveli), a PEGylated compstatin-based C3 therapeutic, as a new treatment for paroxysmal nocturnal hemoglobinuria (PNH) marks a milestone in the history of complement drug discovery. Alm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34147650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33711380", "endSection": "title" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1326, "text": "This article summarizes the milestones in the development of pegcetacoplan leading to this first approval for the treatment of adults with PNH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34342834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33711380", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "The FDA approval of pegcetacoplan (Empaveli), a PEGylated compstatin-based C3 therapeutic, as a new treatment for paroxysmal nocturnal hemoglobinuria (PNH) marks a milestone in the history of complement drug discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34147650", "endSection": "abstract" } ] }, { "body": "What is the activity of a Oligosaccharyltransferases ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31769974", "http://www.ncbi.nlm.nih.gov/pubmed/29178580", "http://www.ncbi.nlm.nih.gov/pubmed/29282902", "http://www.ncbi.nlm.nih.gov/pubmed/33997889", "http://www.ncbi.nlm.nih.gov/pubmed/34493791" ], "ideal_answer": [ "oligosaccharyltransferases (OSTs), which catalyze the attachment of glycans to specific amino acid residues in target proteins" ], "exact_answer": [ "attachment of glycans to specific amino acid residues in target proteins" ], "type": "factoid", "id": "621b78e63a8413c65300003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Oligosaccharyltransferases (OSTs) mediate the en\u00a0bloc transfer of N-glycan intermediates onto the asparagine residue in glycosylation sequons (N-X-S/T, X\u2260P). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29282902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "Protein glycosylation, or the attachment of sugar moieties (glycans) to proteins, is important for protein stability, activity, and immunogenicity. However, understanding the roles and regulations of site-specific glycosylation events remains a significant challenge due to several technological limitations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29178580", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 601, "text": "A particular challenge is the synthesis of oligosaccharyltransferases (OSTs), which catalyze the attachment of glycans to specific amino acid residues in target proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29178580", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Lipid-linked oligosaccharides (LLOs) play an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyltransferases (OSTs), which are responsible for the en bloc transfer of glycan chains onto a nascent polypeptide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31769974", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 399, "text": "Key to bioconjugation are a group of enzymes known as oligosaccharyltransferases (OTases) that transfer polysaccharides to engineered carrier proteins containing conserved amino acid sequences known as sequons. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33997889", "endSection": "abstract" } ] }, { "body": "On what chromosome would the MKKS gene for McKusick-Kaufman(AKA Kaufman-McKusick) syndrome be found?", "_type": "factoid", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10973238", "http://www.ncbi.nlm.nih.gov/pubmed/22090721", "http://www.ncbi.nlm.nih.gov/pubmed/15266619", "http://www.ncbi.nlm.nih.gov/pubmed/10802661" ], "_body": "To what chromosome would the MKKS gene for McKusick-Kaufman(AKA Kaufman-McKusick) syndrome be found?", "ideal_answer": [ "The MKKS gene is mapped to chromosome 20" ], "exact_answer": [ "20", "20p12", "mkks or bbs6 gene on chromosome 20p12", "20p12 between D20S162 and D20S894 markers" ], "type": "factoid", "id": "601eb56c1cb411341a000058", "snippets": [ { "offsetInBeginSection": 235, "offsetInEndSection": 353, "text": "The syndrome is caused by mutations in the MKKS gene mapped onto chromosome 20p12 between D20S162 and D20S894 markers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090721", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 1046, "text": " Both MKS and BBS can be caused by mutations in the MKKS or BBS6 gene on chromosome 20p12 and BBS is also associated with mutations in other genes (BBS1, BBS2, BBS4, and BBS7). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15266619", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1045, "text": "Both MKS and BBS can be caused by mutations in the MKKS or BBS6 gene on chromosome 20p12 and BBS is also associated with mutations in other genes (BBS1, BBS2, BBS4, and BBS7).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15266619", "endSection": "abstract" }, { "offsetInBeginSection": 887, "offsetInEndSection": 1064, "text": "can be caused by mutations in the MKKS or BBS6 gene on chromosome 20p12 and BBS is also associated with mutations in other genes (BBS1, BBS2, BBS4, and BBS7). To address this he", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15266619", "endSection": "abstract" }, { "offsetInBeginSection": 244, "offsetInEndSection": 361, "text": "ome is caused by mutations in the MKKS gene mapped onto chromosome 20p12 between D20S162 and D20S894 markers. Mutatio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22090721", "endSection": "abstract" }, { "offsetInBeginSection": 1803, "offsetInEndSection": 1909, "text": "Genotyping with markers from the MKKS region confirmed homozygosity at 20p12 in both affected individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10973238", "endSection": "abstract" } ] }, { "body": "Which maternal CYP2D6 related phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28696420" ], "ideal_answer": [ "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine." ], "type": "summary", "id": "606add0094d57fd879000055", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28696420", "endSection": "abstract" } ] }, { "body": "Describe the web application VICTOR", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34139436" ], "ideal_answer": [ "VICTOR is a free, dependency-free visual analytics web application that allows the visual comparison of the results of various clustering algorithms. It can handle multiple cluster set results simultaneously and compare them using ten different metrics. Clustering results can be filtered and compared with the use of data tables or interactive heatmaps, bar plots, correlation networks, sankey and circos plots.", "VICTOR is a visual analytics web application which allows the visual comparison of the results of various clustering algorithms.", "VICTOR is the first fully interactive and dependency-free visual analytics web application which allows the visual comparison of the results of various clustering algorithms. VICTOR can handle multiple cluster set results simultaneously and compare them using ten different metrics. Clustering results can be filtered and compared to each other with the use of data tables or interactive heatmaps, bar plots, correlation networks, sankey and circos plots." ], "type": "summary", "id": "62004003c9dfcb9c09000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "VICTOR: A visual analytics web application for comparing cluster sets.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34139436", "endSection": "title" }, { "offsetInBeginSection": 570, "offsetInEndSection": 1647, "text": "To automate this process, in this study, we present VICTOR, the first fully interactive and dependency-free visual analytics web application which allows the visual comparison of the results of various clustering algorithms. VICTOR can handle multiple cluster set results simultaneously and compare them using ten different metrics. Clustering results can be filtered and compared to each other with the use of data tables or interactive heatmaps, bar plots, correlation networks, sankey and circos plots. We demonstrate VICTOR's functionality using three examples. In the first case, we compare five different network clustering algorithms on a Yeast protein-protein interaction dataset whereas in the second example, we test four different parameters of the MCL clustering algorithm on the same dataset. Finally, as a third example, we compare four different meta-analyses with hierarchically clustered differentially expressed genes found to be involved in myocardial infarction. VICTOR is available at http://victor.pavlopouloslab.info or http://bib.fleming.gr:3838/VICTOR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34139436", "endSection": "abstract" } ] }, { "body": "What is GLS-5700?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34525286", "http://www.ncbi.nlm.nih.gov/pubmed/30053014", "http://www.ncbi.nlm.nih.gov/pubmed/28976850" ], "ideal_answer": [ "GLS-5700 is a synthetic, consensus DNA vaccine encoding the ZIKV premembrane and envelope proteins that was tested for Zika virus disease." ], "type": "summary", "id": "61f5fe43882a024a1000001c", "snippets": [ { "offsetInBeginSection": 248, "offsetInEndSection": 482, "text": "ETHODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34525286", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 417, "text": "Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 \u00d7 105 plaque-forming units at 13 weeks of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053014", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 482, "text": "Methods In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28976850", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 419, "text": "thods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 \u00d7 105 plaque-forming units at 13 weeks of age. O", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053014", "endSection": "abstract" }, { "offsetInBeginSection": 249, "offsetInEndSection": 484, "text": "THODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34525286", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 481, "text": "Methods In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28976850", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 489, "text": "ods In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The par", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28976850", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 462, "text": " infection.METHODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34525286", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 397, "text": "cient mice.Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 \u00d7 105 plaque-forming units", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 396, "text": "Background: Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficient mice.Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 \u00d7 105 plaque-forming unit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30053014", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 461, "text": " described. There are no approved vaccines against ZIKV infection.METHODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34525286", "endSection": "abstract" } ] }, { "body": "Is histone variant H3.3K27M associated with gliomas?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32647372", "http://www.ncbi.nlm.nih.gov/pubmed/33155136", "http://www.ncbi.nlm.nih.gov/pubmed/32826850" ], "ideal_answer": [ "Yes,\nDiffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation." ], "exact_answer": "yes", "type": "yesno", "id": "603400051cb411341a00014e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Reciprocal H3.3 gene editing identifies K27M and G34R mechanisms in pediatric glioma including NOTCH signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32647372", "endSection": "title" }, { "offsetInBeginSection": 589, "offsetInEndSection": 703, "text": "Well-known oncohistones, with mutations on both H3.1 and H3.3, include H3K36M in chondroblastoma, H3K27M in glioma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33155136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32826850", "endSection": "abstract" } ] }, { "body": "What is another name for keratomileusis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9848072", "http://www.ncbi.nlm.nih.gov/pubmed/31513041", "http://www.ncbi.nlm.nih.gov/pubmed/23868667", "http://www.ncbi.nlm.nih.gov/pubmed/14991311", "http://www.ncbi.nlm.nih.gov/pubmed/12165712", "http://www.ncbi.nlm.nih.gov/pubmed/30845834", "http://www.ncbi.nlm.nih.gov/pubmed/31478935", "http://www.ncbi.nlm.nih.gov/pubmed/11316017", "http://www.ncbi.nlm.nih.gov/pubmed/23960918", "http://www.ncbi.nlm.nih.gov/pubmed/20398107", "http://www.ncbi.nlm.nih.gov/pubmed/22496438", "http://www.ncbi.nlm.nih.gov/pubmed/23112265" ], "ideal_answer": [ "Report the outcomes of laser in situ keratomileusis (LASIK) for high myopia correction after long-term follow-up", "['Report the outcomes of laser in situ keratomileusis (LASIK) for high myopia correction after long-term follow-up.']", "Laser in situ keratomileusis is also known as LASIK", "Laser in situ keratomileusis (LASIK)" ], "exact_answer": [ "LASIK" ], "type": "factoid", "id": "601ef0571cb411341a000067", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 123, "text": "Report the outcomes of laser in situ keratomileusis (LASIK) for high myopia correction after long-term follow-up", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30845834", "endSection": "abstract" }, { "offsetInBeginSection": 391, "offsetInEndSection": 427, "text": "laser in-situ keratomileusis (LASIK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31513041", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 46, "text": "Laser in situ keratomileusis (LASIK) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31478935", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 545, "text": "Currently laser-assisted in situ keratomileusis (LASIK) is indicated to correct myopia of up to -\u20098\u00a0D, hyperopia up to +\u20093\u00a0D and astigmatism up to 5\u00a0D. Photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK) are primarily recommended for myopia up to -\u20096\u00a0D and for greater refractive errors, phakic intraocular lenses (IOL) are the first choice (myopia greater than -\u20096\u00a0D and hyperopia greater than +\u20093\u00a0D).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23868667", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "PURPOSE: Ectasia after laser in situ keratomileusis (LASIK) is a rare but serious complication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11316017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "BACKGROUND: Laser epithelial keratomileusis (LASEK) is a new keratorefractive procedure for the correction of myopia and myopic astigmatism, which may combine advantages and eliminate disadvantages of photorefractive keratectomy (e.g. pain, corneal haze) and laser in situ keratomileusis (e.g. flap and interface complications, dry eye, keratecta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14991311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Laser subepithelial keratomileusis (LASEK) is a relatively new refractive surgical technique that purportedly combines the advantages of laser in-situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). Li", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12165712", "endSection": "abstract" }, { "offsetInBeginSection": 1019, "offsetInEndSection": 1138, "text": "PRK (photorefractive keratectomy), LASEK (laser epithelial keratomileusis) are good alternatives for glaucoma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23960918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "BACKGROUND: LASIK (Laser in situ keratomileusis) is used in refractive surgery especially for correction of higher degree", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9848072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "LASEK (laser subepithelial keratomileusis).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12165712", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Laser subepithelial keratomileusis (LASEK) is a relatively new refractive surgical technique that purportedly combines the advantages of laser in-situ keratomileusis (LASIK) and photorefractive keratectomy (PRK).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12165712", "endSection": "abstract" }, { "offsetInBeginSection": 1549, "offsetInEndSection": 1664, "text": "The incorporation of a microkeratome in 1990 finally led to laser in situ keratomileusis-LASIK-as we know it today.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22496438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Photorefractive keratectomy, laser epithelial keratomileusis (LASEK) and Epi-LASIK are all variants of a similar type refractive surgery involving laser on the surface of the cornea and differ mainly in management of the epithelium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20398107", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 387, "text": "Although laser in situ keratomileusis (LASIK) is currently the most popular form of refractive surgery, LASEK is the procedure of choice in some patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20398107", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "A 33-year-old man who underwent uneventful laser in situ keratomileusis (LASIK) developed pressure-induced stromal edema resulting in an interface haze in both eyes and a pocket of fluid under the flap of the right eye 10 days after surgery, while receiving topical fluorometholone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23112265", "endSection": "abstract" } ] }, { "body": "In which motif of the RUNX1T1 protein is the rs34269950 SNP located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32589708" ], "ideal_answer": [ "The rs34269950 SNP of RUNX1T1 is located in the 'RRACH' motif." ], "exact_answer": [ "RRACH motif" ], "type": "factoid", "id": "62260afb3a8413c65300007b", "snippets": [ { "offsetInBeginSection": 651, "offsetInEndSection": 878, "text": "Of these SNPs only rs34269950 located in the 'RRACH' motif, the most common N6-methyladenosine (m6A) methylation modification site (recognized by FTO), was significantly associated with obesity risk and metabolic abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589708", "endSection": "abstract" } ] }, { "body": "What is caused by SCUBE3 loss of function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33308444" ], "ideal_answer": [ "SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling.", "SCUBE3 is a BMP2/BMP4 co-receptor. It is responsible for the development of bone and teeth. When it is not functioning properly, it inhibits the growth and development of these tissues.", "SCUBE3 loss-of-function results in a human disease caused by defective function of a member of the SCUBE family that is associated with a previously unrecognized syndromic disorder. The disorder is characterized by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. It is also associated with dysregulating bone morphogenetic protein signaling." ], "type": "summary", "id": "61f86db9882a024a10000045", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308444", "endSection": "title" }, { "offsetInBeginSection": 206, "offsetInEndSection": 1481, "text": "Here we report that bi-allelic inactivating variants in SCUBE3 have pleiotropic consequences on development and cause a previously unrecognized syndromic disorder. Eighteen affected individuals from nine unrelated families showed a consistent phenotype characterized by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. In\u00a0vitro functional validation studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, and their dysregulating effect on bone morphogenetic protein (BMP) signaling. We show that SCUBE3 acts as a BMP2/BMP4 co-receptor, recruits the BMP receptor complexes into raft microdomains, and positively modulates signaling possibly by augmenting the specific interactions between BMPs and BMP type I receptors. Scube3-/- mice showed craniofacial and dental defects, reduced body size, and defective endochondral bone growth due to impaired BMP-mediated chondrogenesis and osteogenesis, recapitulating the human disorder. Our findings identify a human disease caused by defective function of a member of the SCUBE family, and link SCUBE3 to processes controlling growth, morphogenesis, and bone and teeth development through modulation of BMP signaling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33308444", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the CAPOX chemotherapy regimen for colorectal cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33023657", "http://www.ncbi.nlm.nih.gov/pubmed/19949897", "http://www.ncbi.nlm.nih.gov/pubmed/20643620", "http://www.ncbi.nlm.nih.gov/pubmed/31254462", "http://www.ncbi.nlm.nih.gov/pubmed/33790157", "http://www.ncbi.nlm.nih.gov/pubmed/17079693", "http://www.ncbi.nlm.nih.gov/pubmed/32399998", "http://www.ncbi.nlm.nih.gov/pubmed/28174487", "http://www.ncbi.nlm.nih.gov/pubmed/33144447", "http://www.ncbi.nlm.nih.gov/pubmed/27330345", "http://www.ncbi.nlm.nih.gov/pubmed/31832229", "http://www.ncbi.nlm.nih.gov/pubmed/32588749", "http://www.ncbi.nlm.nih.gov/pubmed/32053133", "http://www.ncbi.nlm.nih.gov/pubmed/21063416", "http://www.ncbi.nlm.nih.gov/pubmed/30248163", "http://www.ncbi.nlm.nih.gov/pubmed/33977607", "http://www.ncbi.nlm.nih.gov/pubmed/32994804", "http://www.ncbi.nlm.nih.gov/pubmed/17653254", "http://www.ncbi.nlm.nih.gov/pubmed/29802221", "http://www.ncbi.nlm.nih.gov/pubmed/32156916", "http://www.ncbi.nlm.nih.gov/pubmed/18544957", "http://www.ncbi.nlm.nih.gov/pubmed/34877325", "http://www.ncbi.nlm.nih.gov/pubmed/33215454", "http://www.ncbi.nlm.nih.gov/pubmed/21300933", "http://www.ncbi.nlm.nih.gov/pubmed/17548840", "http://www.ncbi.nlm.nih.gov/pubmed/18361802", "http://www.ncbi.nlm.nih.gov/pubmed/29423680", "http://www.ncbi.nlm.nih.gov/pubmed/33340853" ], "ideal_answer": [ "CAPOX chemotherapy regimen for colorectal cancer includes capecitabine plus oxaliplatin." ], "exact_answer": [ [ "capecitabine" ], [ "oxaliplatin" ] ], "type": "list", "id": "602820fb1cb411341a0000f7", "snippets": [ { "offsetInBeginSection": 434, "offsetInEndSection": 719, "text": "Objective: To assess the noninferiority and toxic effects of 3 vs 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) adjunct chemotherapy among patients with high-risk stage II resected colorectal cancer enrolled in the TOSCA trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32053133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Influence of ABCB-1, ERCC-1 and ERCC-2 gene polymorphisms on response to capecitabine and oxaliplatin (CAPOX) treatment in colorectal cancer (CRC) patients of South India.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32399998", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "WHAT IS KNOWN AND OBJECTIVE: High interindividual response variability was reported with capecitabine and oxaliplatin (CAPOX) regimen in colorectal cancer (CRC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32399998", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 341, "text": "Currently, adjuvant colorectal cancer treatment primarily includes chemotherapeutic regimens such as FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) or CAPOX (capecitabine, oxaliplatin), as well as alternative regimens such as TOMOX (raltitrexed, oxaliplatin). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32588749", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 1070, "text": " The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5)\u2009+\u2009etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33023657", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 652, "text": "Methods: Using the validated PATTERN Markov cohort model, which simulates the disease progression of stage II CC patients from diagnosis to death, we first evaluated a reference strategy in which high-risk patients were treated with chemotherapy for 6\u2009months. In the second strategy, treatment duration was shortened to 3\u2009months. Both strategies were evaluated for CAPOX (capecitabine plus oxaliplatin) and FOLFOX (fluorouracil, leucovorin and oxaliplatin). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32994804", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1333, "text": "The oral fluoropyrimidine capecitabine has been effectively and safely combined with irinotecan (CAPIRI) and/or oxaliplatin (CAPOX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18361802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Prolonged Capecitabine Chemotherapy Following Capecitabine and Oxaliplatin (CAPOX) Regimen Chemotherapy Failed to Improve Survival of Stage III Colorectal Cancer After Radical Resection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31254462", "endSection": "title" }, { "offsetInBeginSection": 832, "offsetInEndSection": 1059, "text": "ents receiving the chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental group and a control group. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34877325", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 768, "text": "LTS: The completion rate of each chemotherapy regimen was 10 out of 16 patients in oral uracil-tegafur plus leucovorin (UFT/LV), 1 out of 3 patients in oral capecitabine (Capecitabine) and 2 out of 14 patients in capecitabine plus oxaliplatin (CAPOX). The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33144447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "BACKGROUND: Capecitabine plus oxaliplatin (CAPOX) is an established treatment option in colorectal cancer, but can be associated with severe t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21063416", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 380, "text": "rent standard treatment for recurrent or metastatic colon cancer uses capecitabine plus oxaliplatin (CAPOX), or continuous-infusion fluorouracil plus oxaliplatin (FOLFOX). This ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19949897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "LESSONS LEARNED: Three-month adjuvant capecitabine plus oxaliplatin in combination (CAPOX) appeared to reduce recurrence, with mild toxicity in postcurative resection of colorectal cancer liver me", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33977607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "WHAT IS KNOWN AND OBJECTIVE: High interindividual response variability was reported with capecitabine and oxaliplatin (CAPOX) regimen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32399998", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 325, "text": "of life. This study evaluated the efficacy and safety of capecitabine plus oxaliplatin (CAPOX) with intermittent oxaliplatin use compared with the standard CAPOX in adjuvant therapy for colon", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33340853", "endSection": "abstract" }, { "offsetInBeginSection": 740, "offsetInEndSection": 953, "text": " combinations are available in NZ in the metastatic setting, with the most popular being oxaliplatin/capecitabine combination (CAPOX) (35%) or irinotecan/5-FU combination (FOLFIRI) (23%). None of the respondents w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653254", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 349, "text": "urrently, adjuvant colorectal cancer treatment primarily includes chemotherapeutic regimens such as FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) or CAPOX (capecitabine, oxaliplatin), as well as alternative regimens such as TOMOX (raltitrexed, oxaliplatin). However,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32588749", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1358, "text": "e capecitabine has been effectively and safely combined with irinotecan (CAPIRI) and/or oxaliplatin (CAPOX). Three randomized phase I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18361802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Background: Capecitabine and oxaliplatin (CAPOX) chemotherapy is a standard treatment for stage 2/3 colore", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31832229", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "[Capecitabine and Oxaliplatin(CAPOX)plus Bevacizumab as Second-Line Chemotherapy for Metastatic Colorectal Cancer].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33790157", "endSection": "title" }, { "offsetInBeginSection": 804, "offsetInEndSection": 1031, "text": "ional Chinese Medicine. Patients receiving the chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental gr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34877325", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 340, "text": "Currently, adjuvant colorectal cancer treatment primarily includes chemotherapeutic regimens such as FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) or CAPOX (capecitabine, oxaliplatin), as well as alternative regimens such as TOMOX (raltitrexed, oxaliplatin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32588749", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 286, "text": "Systemic chemotherapy was administered comprising a capecitabine/oxaliplatin(CAPOX)regimen.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32156916", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 558, "text": "y cycle.METHODS: Thirty-eight colorectal cancer patients scheduled to receive the leucovorin, 5'-fluorouracil, oxaliplatin (FOLFOX) therapy or the capecitabine, oxaliplatin (CAPOX) thera", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29423680", "endSection": "abstract" }, { "offsetInBeginSection": 720, "offsetInEndSection": 927, "text": "Several chemotherapy combinations are available in NZ in the metastatic setting, with the most popular being oxaliplatin/capecitabine combination (CAPOX) (35%) or irinotecan/5-FU combination (FOLFIRI) (23%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Oxaliplatin-based chemotherapy (FOLFOX [folinic acid, fluorouracil, oxaliplatin] or XELOX [oxaliplatin, capecitabine; also called CAPOX]) for 6 months is the current standard for adjuvant therapy of stage III colon cancer patients with good performance status.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30248163", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 458, "text": "al cancers.MATERIALS AND METHODS: Eligibility criteria included diagnosis of colorectal cancers; eligible patients who were scheduled to undergo capecitabine monotherapy or capecitabine-oxaliplatin (CAPOX) fo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29802221", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "BACKGROUND: Despite lack of a true comparative study, the folfox (5-fluorouracil-leucovorin-oxaliplatin) and capox (capecitabine-oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage iii colorectal cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27330345", "endSection": "abstract" }, { "offsetInBeginSection": 493, "offsetInEndSection": 656, "text": "he CAPOX regimen consisted of capecitabine (1000 mg/m2, in 2 divided doses for 14 d) and oxaliplatin (130 mg/m2 given on Day 1), repeated every 21 d for 8 cycles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33215454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Modified CAPOX (capecitabine plus oxaliplatin) regimen every two weeks as second-line treatment in patients with advanced colorectal cancer previously treated with irinotecan-based frontline therapy: a multicenter phase II study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18544957", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Phase II trial of capecitabine and oxaliplatin (CAPOX) plus cetuximab in patients with metastatic colorectal cancer who progressed after oxaliplatin-based chemotherapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17079693", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "LESSONS LEARNED: Three-month adjuvant capecitabine plus oxaliplatin in combination (CAPOX) appeared to reduce recurrence, with mild toxicity in postcurative resection of colorectal cancer liver ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33977607", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "BACKGROUND: To evaluate the efficacy and tolerance of capecitabine (CAP) given every other week and biweekly oxaliplatin (OX; modified CAPOX regimen) in patients with advanced colorectal cancer previously treated with irinote- can-based frontline chemotherapy.METHODS: Sixty-seven patients were enrolled; the median age was 62 years and 62 (92.5%) had a performance ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18544957", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 527, "text": "PURPOSE: To compare the use of capecitabine plus oxaliplatin (CAPOX) with infusional fluorouracil (FU)/folinic acid plus oxaliplatin (FUFOX) as first-line therapy for patients with metastatic colorectal cancer (MCRC).PATIENTS AND METHODS: A total of 474 patients with MCRC received either CAPOX (capecitabine 1,000 mg/m2 bid, days 1 to 14 plus oxaliplatin 70 mg/m2 days 1 and 8, repeated every 22 days) ) or FUFOX (oxaliplatin 50 mg/m2 followed by leucovorin 500 mg/m2 plus FU 2,000 mg/m2 as a 22-hour infusion days 1, 8, 15, a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17548840", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "OBJECTIVE: The aim of this prospective, single-arm phase II trial was to confirm the safety and efficacy of neoadjuvant chemotherapy (NAC) using oxaliplatin plus capecitabine (CapOX) for patients with operable locally advanced colon cancer (CC).METHODS: Patients with computed tomography-defined T4 or lymph node-positiv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28174487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "PURPOSE: Capecitabine has shown similar efficacy to 5-fluorouracil (5-FU); a regimen containing 2 weeks of capecitabine/oxaliplatin (CapOx) has demonstrated noninferiority to infusional 5-FU/oxaliplatin/leucovorin (FOLFOX) for the treatment of metastatic colorectal cance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20643620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 616, "text": "PURPOSE: The AIO KRK-0104 randomized phase II trial investigated the efficacy and safety of cetuximab combined with capecitabine and irinotecan (CAPIRI) or capecitabine and oxaliplatin (CAPOX) in the first-line treatment of metastatic colorectal cancer (mCRC).PATIENTS AND METHODS: A total of 185 patients with mCRC were randomly assigned to cetuximab (400 mg/m(2) day 1, followed by 250 mg/m(2) weekly) plus CAPIRI (irinotecan 200 mg/m(2), day 1; capecitabine 800 mg/m(2) twice daily days 1 through 14, every 3 weeks; or cetuximab plus CAPOX (oxaliplatin 130 mg/m(2) day 1; capecitabine 1,000 mg/m(2) twice daily da", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "BACKGROUND: Despite lack of a true comparative study, the folfox (5-fluorouracil-leucovorin-oxaliplatin) and capox (capecitabine-oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage iii colore", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27330345", "endSection": "abstract" } ] }, { "body": "Is FKBP52 encoding a chaperone ?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32612187", "http://www.ncbi.nlm.nih.gov/pubmed/33184939", "http://www.ncbi.nlm.nih.gov/pubmed/30483787" ], "ideal_answer": [ "Yes,\nFKBP52 is a co-chaperone." ], "exact_answer": "yes", "type": "yesno", "id": "6081a83f4e6a4cf630000007", "snippets": [ { "offsetInBeginSection": 62, "offsetInEndSection": 95, "text": "Hsp90 co-chaperones Pp5 and FKBPs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32612187", "endSection": "title" }, { "offsetInBeginSection": 137, "offsetInEndSection": 187, "text": "The co-chaperone FK506-binding protein 51 (FKBP51)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33184939", "endSection": "abstract" }, { "offsetInBeginSection": 2162, "offsetInEndSection": 2182, "text": "co\u2011chaperone FKBP52 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30483787", "endSection": "abstract" } ] }, { "body": "Isotocin is an homolog of what hormone?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21112347", "http://www.ncbi.nlm.nih.gov/pubmed/32071244", "http://www.ncbi.nlm.nih.gov/pubmed/28927876", "http://www.ncbi.nlm.nih.gov/pubmed/26064593", "http://www.ncbi.nlm.nih.gov/pubmed/33141148", "http://www.ncbi.nlm.nih.gov/pubmed/16691572", "http://www.ncbi.nlm.nih.gov/pubmed/21104292", "http://www.ncbi.nlm.nih.gov/pubmed/32303866", "http://www.ncbi.nlm.nih.gov/pubmed/18366747" ], "ideal_answer": [ "Isotocin is a homolog of oxytocin." ], "exact_answer": [ "oxytocin" ], "type": "factoid", "id": "603bc2801cb411341a00015a", "snippets": [ { "offsetInBeginSection": 293, "offsetInEndSection": 472, "text": " comprising the vast majority of vertebrate species, remains unclear. To address this issue, we evaluated the involvement of an oxytocin homolog (isotocin, referred herein as oxt)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32071244", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 196, "text": "However, in fishes, the effect of isotocin, the homologue of oxytocin, on social behaviour is less clear", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32303866", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 921, "text": "isotocin may have a homologous role to oxytocin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32303866", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 327, "text": " The present study examined the possible involvement of isotocin (Ist), an oxytocin-like neuropeptide, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33141148", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 545, "text": "The vasopressin homolog in non-mammalian vertebrates is vasotocin; and the oxytocin homolog is mesotocin in non-eutherian tetrapods, mesotocin and [Phe2]mesotocin in lungfishes, and isotocin in ray-finned fishes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18366747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "The nonapeptides arginine vasopressin (AVP; including its non-mammalian homolog arginine vasotocin, AVT) and oxytocin (OT; including its non-mammalian homologs mesotocin, MT, and isotocin, IT) regulate social behavior, including aggression and reproduction, via receptors conserved across vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21112347", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 673, "text": "the current study, we focused on the comparative neuroendocrine functions and regulation of isotocin, the teleost homologue of mammalian oxytocin. Spe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28927876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The present study using zebrafish as a model explores the role of isotocin, a homolog of oxytocin, in controlling ion regulatory mechanisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21104292", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 248, "text": "eost fishes possess vasopressin and oxytocin homologues known as arginine vasotocin (AVT) and isotocin (IT), respectively. The r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26064593", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 808, "text": "Isotocin, which is homologous to oxytocin, is expressed early, in a simple pattern in the developing zebrafish brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16691572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The present study using zebrafish as a model explores the role of isotocin, a homolog of oxytocin, in controlling ion regulatory mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21104292", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 964, "text": "Our study provides some of the first evidence of a pro-social effects of isotocin in a fish and suggests that in fishes, isotocin may have a homologous role to oxytocin, at least in promoting shoaling behaviour.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32303866", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 197, "text": "However, in fishes, the effect of isotocin, the homologue of oxytocin, on social behaviour is less clear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32303866", "endSection": "abstract" } ] }, { "body": "Fingolimod is a selective antagonist for which molecule?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30776422" ], "ideal_answer": [ "Fingolimod is a selective S1P1 functional antagonist by induction of irreversible S1P1 internalization and degradation." ], "exact_answer": [ "S1P1" ], "type": "factoid", "id": "6052729c94d57fd879000011", "snippets": [ { "offsetInBeginSection": 1111, "offsetInEndSection": 1375, "text": "Pharmacologically, fingolimod was characterized as a non-selective agonist of all of the S1P receptors (S1PR), with the exception of S1P2, and in addition, as a selective S1P1 functional antagonist by induction of irreversible S1P1 internalization and degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30776422", "endSection": "abstract" } ] }, { "body": "Does \u03b1CGRP have amyloidogenic properties?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29501724" ], "ideal_answer": [ "Yes. \u03b1CGRP, a 37-residue-long peptide hormone, is a novel amyloidogenic member of the CGRP family", "Yes, it has amyloidogenic properties. It is a member of the CGRP family." ], "exact_answer": "yes", "type": "yesno", "id": "62004357c9dfcb9c09000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "\u03b1CGRP, another amyloidogenic member of the CGRP family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501724", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 873, "text": "Therefore, in this work, we investigated the amyloidogenic profile of \u03b1CGRP, a 37-residue-long peptide hormone, utilizing both biophysical experimental techniques and Molecular Dynamics simulations. These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the \u03b1CGRP polymerization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29501724", "endSection": "abstract" } ] }, { "body": "Is istiratumab effective for pancreatic cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31912800" ], "ideal_answer": [ "No. In clinical trial, istiratumab failed to improve efficacy of standard of care for pancreatic cancer." ], "exact_answer": "no", "type": "yesno", "id": "60282c3f1cb411341a0000fe", "snippets": [ { "offsetInBeginSection": 1862, "offsetInEndSection": 1963, "text": "CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31912800", "endSection": "abstract" } ] }, { "body": "What is the human proteoform project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34767442", "http://www.ncbi.nlm.nih.gov/pubmed/32118252", "http://www.ncbi.nlm.nih.gov/pubmed/34539228", "http://www.ncbi.nlm.nih.gov/pubmed/34047392", "http://www.ncbi.nlm.nih.gov/pubmed/34472376", "http://www.ncbi.nlm.nih.gov/pubmed/32967423" ], "ideal_answer": [ "Top-down proteomics is emerging as a preferred approach to investigate biological systems, with objectives ranging from the detailed assessment of a single protein therapeutic, to the complete characterization of every possible protein including their modifications, which define the human proteoform." ], "type": "summary", "id": "621b99973a8413c653000045", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Top-down proteomics is emerging as a preferred approach to investigate biological systems, with objectives ranging from the detailed assessment of a single protein therapeutic, to the complete characterization of every possible protein including their modifications, which define the human proteoform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34047392", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 729, "text": "intact mass data are readily deconvoluted using well-known software options, the analysis of fragmentation data that result from a tandem MS experiment - essential for proteoform characterization - is not yet standardized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34539228", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Background ApoAI (apolipoproteins AI) and apoAII (apolipoprotein AII) are structural and functional proteins of high-density lipoproteins (HDL) which undergo post-translational modifications at specific residues, creating distinct proteoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34472376", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 567, "text": ". Characterizing proteoforms involves identifying and locating primary structure alterations (PSAs) in proteoforms, which is of practical importance for the advancement of the medical profession. With the development of mass spectrometry (MS) technology, the characterization of proteoforms based on top-down MS technology has become possible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32118252", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Proteoforms are the workhorses of the cell, and subtle differences between their amino acid sequences or post-translational modifications (PTMs) can change their biological function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32967423", "endSection": "abstract" } ] }, { "body": "Telomestatin is derived from what organism?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27632666", "http://www.ncbi.nlm.nih.gov/pubmed/11878947", "http://www.ncbi.nlm.nih.gov/pubmed/34285374", "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "http://www.ncbi.nlm.nih.gov/pubmed/12810655" ], "ideal_answer": [ "Telomestatin is a natural macrocyclic compound derived from Streptomyces anulatus 3533-SV4" ], "exact_answer": [ "Streptomyces anulatus" ], "type": "factoid", "id": "622118a43a8413c65300006a", "snippets": [ { "offsetInBeginSection": 388, "offsetInEndSection": 478, "text": "Telomestatin is a natural macrocyclic compound derived from Streptomyces anulatus 3533-SV4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34285374", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 479, "text": "Telomestatin is a natural macrocyclic compound derived from Streptomyces anulatus 3533-SV4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34285374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11878947", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 754, "text": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor through its G-quadruplex interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12810655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Telomestatin, a natural product isolated from Streptomyces anulatus, stabilizes telomeric DNA G-quadruplexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27632666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "endSection": "abstract" } ] }, { "body": "Which plant is khellin extracted from?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24925412" ], "ideal_answer": [ "Khellin is extracted from the seeds of the plant Ammi visnaga." ], "exact_answer": [ "Ammi visnaga" ], "type": "factoid", "id": "6206d06ec9dfcb9c09000041", "snippets": [ { "offsetInBeginSection": 142, "offsetInEndSection": 322, "text": "The first chromone in clinical use, khellin, was extracted from the seeds of the plant Ammi visnaga, and had been used for centuries as a diuretic and as a smooth muscle relaxant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925412", "endSection": "abstract" } ] }, { "body": "Describe ANTISOMA", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32468552" ], "ideal_answer": [ "The ANTISOMA method is a computerized pipeline for the reduction of the aggregation tendency of monoclonal antibodies (mAbs) based on an automated amino acid substitution approach. The method is available online at http://bioinformatics.biol.uoa.gr/antisoma.", "ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability.", "ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach.", "ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability. The method is available online at http://bioinformatics.biol.uoa.gr/ANTISOMA ." ], "type": "summary", "id": "620058b3c9dfcb9c09000016", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "ANTISOMA: A Computational Pipeline for the Reduction of the Aggregation Propensity of Monoclonal Antibodies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32468552", "endSection": "title" }, { "offsetInBeginSection": 462, "offsetInEndSection": 963, "text": "ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability. The method is available online at http://bioinformatics.biol.uoa.gr/ANTISOMA .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32468552", "endSection": "abstract" } ] }, { "body": "Which factors are inhibited by Abelacimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34297496", "http://www.ncbi.nlm.nih.gov/pubmed/34714969" ], "ideal_answer": [ "Abelacimab is a novel dual inhibitor of Factor XI and Factor XIa." ], "exact_answer": [ [ "XI" ], [ "XIa" ] ], "type": "list", "id": "61f5f0e1882a024a10000014", "snippets": [ { "offsetInBeginSection": 108, "offsetInEndSection": 230, "text": "Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34297496", "endSection": "abstract" }, { "offsetInBeginSection": 1576, "offsetInEndSection": 1779, "text": "Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34297496", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34714969", "endSection": "title" }, { "offsetInBeginSection": 155, "offsetInEndSection": 335, "text": "Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34714969", "endSection": "abstract" }, { "offsetInBeginSection": 1582, "offsetInEndSection": 1784, "text": " XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Fund", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34297496", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 327, "text": " events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34714969", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 220, "text": "uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) con", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34297496", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 677, "text": "lic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI.OBJECTIVES: To investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous and multiple dose subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively.PATIENTS/METHODS: In study ANT-003, healthy volunteers were administered single intravenous d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34714969", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 542, "text": " uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.METHODS: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34297496", "endSection": "abstract" } ] }, { "body": "What is vesiduction?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32363801", "http://www.ncbi.nlm.nih.gov/pubmed/32784449" ], "ideal_answer": [ "'Vesiduction' as a fourth mode of intercellular DNA transfer." ], "exact_answer": [ "'Vesiduction' as a fourth mode of intercellular DNA transfer." ], "type": "factoid", "id": "603219c21cb411341a000133", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Besides the canonical gene transfer mechanisms transformation, transduction and conjugation, DNA transfer involving extracellular vesicles is still under appreciated. However, this widespread phenomenon has been observed in the three domains of life. Here, we propose the term 'Vesiduction' as a fourth mode of intercellular DNA transfer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32363801", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1028, "text": "In this review, we first summarize the major pathways of HGT in bacteria, including conjugation, transformation, transduction and vesiduction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32784449", "endSection": "abstract" } ] }, { "body": "What is the route of administration of eptinezumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32266704" ], "ideal_answer": [ "Eptinezumab is administered intravenously." ], "exact_answer": [ "Intravenously" ], "type": "factoid", "id": "6026f0251cb411341a0000d6", "snippets": [ { "offsetInBeginSection": 267, "offsetInEndSection": 415, "text": "Eptinezumab, delivered by intravenous (IV) administration, is being developed by Lundbeck Seattle BioPharmaceuticals for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32266704", "endSection": "abstract" } ] }, { "body": "What kind of approaches you need to combine in order to manage Familial spontaneous pneumothorax?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34145047" ], "ideal_answer": [ "Clinical, radiological and genetic approaches", "Combining clinical, radiological and genetic approaches to pneumothorax management is a critical step in managing family history and family history-based causes of spontaneous pneumothorsic disease (FPSD) in children and adults who have a family history of FPSD and are at high risk for the disease because of family history." ], "exact_answer": [ [ "Clinical" ], [ "Radiological" ], [ "Genetic" ] ], "type": "list", "id": "61f81912882a024a10000041", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Combining clinical, radiological and genetic approaches to pneumothorax management.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34145047", "endSection": "title" } ] }, { "body": "What is the mechanism of action of Vericiguat?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31096775", "http://www.ncbi.nlm.nih.gov/pubmed/32458378", "http://www.ncbi.nlm.nih.gov/pubmed/34074190", "http://www.ncbi.nlm.nih.gov/pubmed/32749493", "http://www.ncbi.nlm.nih.gov/pubmed/34291399", "http://www.ncbi.nlm.nih.gov/pubmed/32222134", "http://www.ncbi.nlm.nih.gov/pubmed/33770393", "http://www.ncbi.nlm.nih.gov/pubmed/33032741", "http://www.ncbi.nlm.nih.gov/pubmed/29032136", "http://www.ncbi.nlm.nih.gov/pubmed/34431706", "http://www.ncbi.nlm.nih.gov/pubmed/33030703", "http://www.ncbi.nlm.nih.gov/pubmed/34478114", "http://www.ncbi.nlm.nih.gov/pubmed/33850913", "http://www.ncbi.nlm.nih.gov/pubmed/28586537", "http://www.ncbi.nlm.nih.gov/pubmed/33395323", "http://www.ncbi.nlm.nih.gov/pubmed/34157357", "http://www.ncbi.nlm.nih.gov/pubmed/27545139", "http://www.ncbi.nlm.nih.gov/pubmed/34086190", "http://www.ncbi.nlm.nih.gov/pubmed/34410527" ], "ideal_answer": [ "Vericiguat is a stimulator of soluble guanylate cyclase. It was developed for treatment of chronic heart failure with reduced ejection fraction." ], "type": "summary", "id": "601cbbf11cb411341a00002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32458378", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "BACKGROUND: Vericiguat is a stimulator of soluble guanylate cyclase currently under investigation as a first-in-class therapy for worsening chronic heart failure (NCT02861534). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32458378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32222134", "endSection": "abstract" }, { "offsetInBeginSection": 1461, "offsetInEndSection": 1788, "text": "More recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors have further improved disease outcomes, significantly reducing cardiovascular and all-cause mortality irrespective of diabetes status, and vericiguat, a soluble guanylate cyclase stimulator, reduces heart failure hospitalization in high-risk patients with HFrEF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32749493", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1245, "text": "Following the positive results of the phase 3 VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial on the sGC stimulator vericiguat in HFrEF, the main open questions are the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF and of vericiguat in HFpEF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33032741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "BACKGROUND: Vericiguat, a direct stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for symptomatic chronic heart failure (HF) and ejection fraction\u2009<\u200945%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33030703", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 877, "text": "Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, and then exert a more physiological action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34291399", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 864, "text": "Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34410527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 455, "text": "Background The VITALITY-HFpEF trial (Evaluate the Efficacy and Safety of the Oral sGC Stimulator Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With Heart Failure and Preserved Ejection Fraction) is designed to determine the efficacy and safety of a novel oral soluble guanylate cyclase stimulator, vericiguat, on quality of life and exercise tolerance in heart failure patients with preserved ejection fraction (HFpEF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31096775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "BACKGROUND: Vericiguat is a stimulator of soluble guanylate cyclase currently under investigation as a first-in-class therapy for worsening chronic heart failure (NCT02861534).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32458378", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 680, "text": "EAS COVERED: The authors review the available data on the mechanism of action of vericiguat (cyclic guanosine monophosphate (cGMP) pathway), its clinical development program, its role in HF management, and its future positioning in the therapeutic recommendations.EX", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34074190", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1023, "text": "Omecamtiv mecarbil, an inotropic agent that improves myocardial contractility by a novel mechanism, and vericiguat, a drug that stimulates soluble guanylate cyclase, are both being developed to treat patients with chronic HF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27545139", "endSection": "abstract" }, { "offsetInBeginSection": 505, "offsetInEndSection": 722, "text": "fter the first generation of sGC stimulators like riociguat or lificiguat, new compound classes with different physicochemical and kinetic profiles were identified, like the sGC stimulators vericiguat or praliciguat.A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33395323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431706", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "AIMS: Exploratory assessment of the potential benefits of the novel soluble guanylate cyclase stimulator vericiguat on health status in patients with heart failure (HF) with preserved ejection frac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28586537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), has shown promising results in patients with heart failure and reduced ejection fraction (HFrEF) in the recent VICTORIA trial. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34478114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "BACKGROUND: Vericiguat, a stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for worsening chronic heart failure in adults with left ventricular ejection fra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34086190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND: Vericiguat is a stimulator of soluble guanylate cyclase currently under investigation as a first-in-class therapy for worsening chronic heart failure (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32458378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BACKGROUND: Vericiguat, a direct stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for symptomatic chronic heart failure (HF) and ejection fract", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33030703", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 861, "text": "sion. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological acti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34410527", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 896, "text": "stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, and then exert a more physiological action. The phase 3 VICTOR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34291399", "endSection": "abstract" }, { "offsetInBeginSection": 670, "offsetInEndSection": 832, "text": "Vericiguat has a dual mode of action on this axis, it both sensitizes sGC to low levels of NO, and can directly stimulate sGC in the absence of any endogenous NO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34478114", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 629, "text": "Vericiguat is an oral soluble guanylate cyclase stimulator that enhances the cyclic guanosine monophosphate (GMP) pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34157357", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1105, "text": "ielded conflicting results in HF patients. Vericiguat acts as a sGC stimulator thus targeting the NO-sGC-cGMP pathway by a different mechanism that comp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34074190", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 296, "text": "Vericiguat stimulates sGC and cGMP production independent of nitric oxide (NO) and enhances the effects of NO by stabilizing the NO-sGC binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33770393", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 996, "text": "Vericiguat is an oral guanylate cyclase stimulator that through the recent VICTORIA trial showed a 10% relative difference in death from cardiovascular cause or hospitalization for heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33850913", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1103, "text": " yielded conflicting results in HF patients. Vericiguat acts as a sGC stimulator thus targeting the NO-sGC-cGMP pathway by a different mechanism that co", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34074190", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 743, "text": "utic options. In the last year, the soluble guanylate cyclase (sGC) stimulator, vericiguat, has drawn the attention of the medical community following the report of reduced clinical outcomes in patients with worsening chronic HF (WCHF).AREAS COVERED: The authors review the available data on the mechanism of action of vericiguat (cyclic guanosine monophosphate (cGMP) pathway), its clinical development program, its role in HF management, and its future positioning in the therapeutic recommendations.EXPERT OPINION: cGMP deficiency has deleterious effects on the he", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34074190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "BACKGROUND: Vericiguat is a stimulator of soluble guanylate cyclase currently under investigation as a first-in-class therapy for worsening chronic heart failure (N", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32458378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Vericiguat (VERQUVO\u2122; Merck & Co, Bayer AG) is a soluble guanylate cyclase (sGC) stimulator being developed for the treatment of chronic heart failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33770393", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1063, "text": "Vericiguat has been shown to directly stimulate sGC and enhance sGC sensitivity to endogenous NO.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29032136", "endSection": "abstract" }, { "offsetInBeginSection": 1220, "offsetInEndSection": 1598, "text": " new treatment option for those in whom rehospitalization or recurrent outpatient intravenous diuretic treatment is a concern. Given high rates of nonadherence in HF patients, vericiguat represents an additional treatment option, especially for patients who do not tolerate available HF therapies.CONCLUSION: Vericiguat is a novel soluble guanylate cyclase stimulator that is sa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), has shown promising results in patients with heart failure and reduced ejection fraction (HFrEF) in the recent VICTORIA trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34478114", "endSection": "abstract" } ] }, { "body": "What is the origin of HEp-2 cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30702281", "http://www.ncbi.nlm.nih.gov/pubmed/25658113", "http://www.ncbi.nlm.nih.gov/pubmed/32409089", "http://www.ncbi.nlm.nih.gov/pubmed/32384969" ], "ideal_answer": [ "human larynx epidermoid carcinoma cell line (HEp-2)" ], "exact_answer": [ "human larynx epidermoid carcinoma cell line" ], "type": "factoid", "id": "606b648394d57fd879000069", "snippets": [ { "offsetInBeginSection": 245, "offsetInEndSection": 276, "text": "oropharyngeal carcinoma (HEp-2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32409089", "endSection": "abstract" }, { "offsetInBeginSection": 376, "offsetInEndSection": 410, "text": "oropharyngeal cancer cells (HEp-2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32384969", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 404, "text": " human larynx epidermoid carcinoma cell line (HEp-2) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30702281", "endSection": "abstract" }, { "offsetInBeginSection": 334, "offsetInEndSection": 363, "text": "HEp-2 laryngeal cancer cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25658113", "endSection": "abstract" } ] }, { "body": "Does bleomycin cause lung toxicity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26834240", "http://www.ncbi.nlm.nih.gov/pubmed/30464999", "http://www.ncbi.nlm.nih.gov/pubmed/17034512", "http://www.ncbi.nlm.nih.gov/pubmed/7679991", "http://www.ncbi.nlm.nih.gov/pubmed/7679525", "http://www.ncbi.nlm.nih.gov/pubmed/1690503", "http://www.ncbi.nlm.nih.gov/pubmed/29269387", "http://www.ncbi.nlm.nih.gov/pubmed/83311", "http://www.ncbi.nlm.nih.gov/pubmed/15992893", "http://www.ncbi.nlm.nih.gov/pubmed/1696541", "http://www.ncbi.nlm.nih.gov/pubmed/27241272", "http://www.ncbi.nlm.nih.gov/pubmed/30398042", "http://www.ncbi.nlm.nih.gov/pubmed/1711838", "http://www.ncbi.nlm.nih.gov/pubmed/6167758", "http://www.ncbi.nlm.nih.gov/pubmed/28121640", "http://www.ncbi.nlm.nih.gov/pubmed/32079853", "http://www.ncbi.nlm.nih.gov/pubmed/27190828", "http://www.ncbi.nlm.nih.gov/pubmed/6165468", "http://www.ncbi.nlm.nih.gov/pubmed/21602446", "http://www.ncbi.nlm.nih.gov/pubmed/2425242", "http://www.ncbi.nlm.nih.gov/pubmed/10783125", "http://www.ncbi.nlm.nih.gov/pubmed/9806661", "http://www.ncbi.nlm.nih.gov/pubmed/25951185", "http://www.ncbi.nlm.nih.gov/pubmed/25026360", "http://www.ncbi.nlm.nih.gov/pubmed/2413151", "http://www.ncbi.nlm.nih.gov/pubmed/2582337", "http://www.ncbi.nlm.nih.gov/pubmed/31809714", "http://www.ncbi.nlm.nih.gov/pubmed/12771616", "http://www.ncbi.nlm.nih.gov/pubmed/31673206", "http://www.ncbi.nlm.nih.gov/pubmed/26888428", "http://www.ncbi.nlm.nih.gov/pubmed/24195693", "http://www.ncbi.nlm.nih.gov/pubmed/2449257", "http://www.ncbi.nlm.nih.gov/pubmed/30755913", "http://www.ncbi.nlm.nih.gov/pubmed/1689606", "http://www.ncbi.nlm.nih.gov/pubmed/6192740", "http://www.ncbi.nlm.nih.gov/pubmed/2443992", "http://www.ncbi.nlm.nih.gov/pubmed/33647319", "http://www.ncbi.nlm.nih.gov/pubmed/28185527", "http://www.ncbi.nlm.nih.gov/pubmed/6205617", "http://www.ncbi.nlm.nih.gov/pubmed/30902828" ], "ideal_answer": [ "Pulmonary toxicity is a devastating complication of bleomycin chemotherapy." ], "exact_answer": "yes", "type": "yesno", "id": "601efda31cb411341a000069", "snippets": [ { "offsetInBeginSection": 32, "offsetInEndSection": 68, "text": "bleomycin-induced pulmonary fibrosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31809714", "endSection": "title" }, { "offsetInBeginSection": 436, "offsetInEndSection": 470, "text": "bleomycin (BLM)-induced pulmonary ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31809714", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Pulmonary toxicity is a devastating complication of bleomycin chemotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28121640", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 335, "text": "Bleomycin containing regimen is routinely employed in the treatment of HL. Pulmonary toxicity due to this drug is the most feared side effect in these regimens where the mortality rate is approximately 2%-3%. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31673206", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 364, "text": "Bleomycin might cause pulmonary fibrosis at higher cumulative doses as toxic effect directly to the lungs or most likely in addition by the formation of vascular microthrombi.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6167758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "The comparative pulmonary toxicity induced by bleomycin and talisomycin (former trivial name: tallysomycin A) was evaluated by measuring lung hydroxyproline content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6165468", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 918, "text": "Clinicians should always remember that bleomycin toxicity may lead to fatal complications in patients with comorbid conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30398042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "CONTEXT: The application of bleomycin is limited due to its side effects including lung toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25026360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Bleomycin is an antineoplastic agent that causes a dose-related lung fibrosis that limits its therapeutic effectiveness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2413151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Acute Lung Toxicity After Intralesional Bleomycin Sclerotherapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29269387", "endSection": "title" }, { "offsetInBeginSection": 233, "offsetInEndSection": 366, "text": "We report a case of a severe acute lung toxicity after a low dose of a second bleomycin intralesional injection in a 5-year-old girl.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29269387", "endSection": "abstract" }, { "offsetInBeginSection": 1039, "offsetInEndSection": 1178, "text": "Renal damage, following cisplatin administration, with subsequent accumulation of bleomycin was the likely cause of the high lung toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1690503", "endSection": "abstract" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1379, "text": "Whenever possible, bleomycin should precede cisplatin infusion to minimize the risk of lung toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1690503", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 311, "text": "The most severe form of BLM-induced pulmonary toxicity is lung fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26888428", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 952, "text": "Results from this study suggest that an excess production of superoxide anions by alveolar macrophages may be the underlying cause of bleomycin pulmonary toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2425242", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Bleomycin lung toxicity is well established and can manifest as bleomycin-induced pneumonitis, but pneumomediastinum and pneumothorax are very rare complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30755913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "High doses of bleomycin administered to patients with lymphomas and other tumors lead to significant lung toxicity in general, and to apoptosis of epithelial cells, in particular. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25951185", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 521, "text": "sis of bleomycin-induced lung toxicity is based on the combination of clinical and radiological features, and requires to rule out differential diagnoses including pneumocystis. \"Bleo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27241272", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Ther", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26834240", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 647, "text": "s studies have proposed that the lung toxicity caused by bleomycin is related to the C-terminal regions of these drugs, which have been shown to closely interact with DNA in metal-bleomycin-DNA complexes. Some o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30464999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "OBJECTIVES: Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain pat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32079853", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 691, "text": "e been no respiratory problems attributable to bleomycin lung toxicity in this study compared with four (3 associated with patient deaths) seen in 91 previously treated patients. The relat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2449257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 44, "text": "Mechanisms of bleomycin-induced lung damage.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1711838", "endSection": "title" }, { "offsetInBeginSection": 429, "offsetInEndSection": 640, "text": "Previous studies have proposed that the lung toxicity caused by bleomycin is related to the C-terminal regions of these drugs, which have been shown to closely interact with DNA in metal-bleomycin-DNA complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30464999", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1582, "text": "g V30 cutoff value of 32% was estimated.CONCLUSION: Bleomycin and RT may cause lung injury ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24195693", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 731, "text": "Postmortem lung studies were performed in all six patients and revealed findings compatible with bleomycin-induced lung toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1690503", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 215, "text": "However, the cytotoxic effects of bleomycin cause a number of adverse responses, in particular in the lung and the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17034512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Bleomycin, a widely used anti-cancer drug, may give rise to pulmonary fibrosis, a serious side effect which is associated with significant morbidity and mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30902828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Bleomycin is a cancer therapeutic known to cause lung injury which progresses to fibrosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33647319", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 393, "text": "and repair. Bleomycin pulmonary toxicity is mediated, at least in part, by the generation of active oxy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9806661", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 352, "text": "This report suggests that bleomycin lung toxicity may be reversible if treated aggressively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7679525", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 706, "text": "Although all bleomycin-treated animals had some evidence of lung toxicity, histologic examination of the lungs revealed markedly reduced bleomycin toxicity in the rats exposed to hypoxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6205617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Low temperature inhibits bleomycin lung toxicity in the rat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6192740", "endSection": "title" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1539, "text": "Results at day 22, 3 wk after bleomycin treatment, showed that airway delivery of liposomes before and after intratracheal administration of bleomycin significantly reduced bleomycin-induced lung toxicity as evidenced by less body weight loss, chronic lung inflammation, and fibrosis as well as improved lung compliance compared with controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21602446", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Protective effect of hypoxia on bleomycin lung toxicity in the rat.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6205617", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "N-acetyl cysteine (NAC) has recently been shown to have antioxidant properties, and since bleomycin produces pulmonary damage via free oxygen radical toxicity, the possible protective effect of NAC on bleomycin lung toxicity was investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2582337", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 620, "text": "All rats treated with bleomycin only had typical changes of bleomycin lung toxicity whereas the animals treated with bleomycin and NAC had minimal pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2582337", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1378, "text": "atic compliance on day 15 was severely decreased with bleomycin alone and showed a further significant decrease when granulocyte colony-stimulating factor was added (controls, 3.85 +/- 0.14 mL/kPa; bleomycin, 1.44 +/- 0.06 mL/kPa; and bleomycin + granulocyte colony-stimulating factor, 0.65 +/- 0.09 mL/kPa; control vs. bleomycin, p <.0001; and bleomycin vs. bleomycin + granulocyte colony-stimulating factor, p =.0003). Lung m", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12771616", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 256, "text": "Bleomycin sometimes causes fatal pulmonary toxicity, including bleomycin-induced pneumonitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15992893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Bleomycin is an antineoplastic agent causing fatal pulmonary toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28185527", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Pulmonary toxicity is an important adverse effect of bleomycin treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2443992", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 185, "text": "Pulmonary toxicity is the most significant complication of bleomycin administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1689606", "endSection": "abstract" }, { "offsetInBeginSection": 1375, "offsetInEndSection": 1565, "text": "It is possible, however, that the low incidence of clinically significant and fatal pulmonary toxicity, as experienced in this group of patients, may be related to the infusion of bleomycin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1689606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Bleomycin-mediated pulmonary toxicity: evidence for a p53-mediated response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10783125", "endSection": "title" }, { "offsetInBeginSection": 639, "offsetInEndSection": 735, "text": "Occurrence of bleomycin lung toxicity requires an immediate and often permanent discontinuation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27241272", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 436, "text": "All three developed bleomycin induced pulmonary toxicity in the form of pulmonary fibrosis during treatment of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27190828", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 203, "text": "One of the fatal side effect of bleomycin is pulmonary toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27190828", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Pulmonary Toxicity of Bleomycin - A Case Series from a Tertiary Care Center in Southern India.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27190828", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Bleomycin is potentially capable of inducing a diffuse interstitial fibrosis of the lung, the pathogenesis of which has not yet been elucidated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/83311", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 748, "text": "Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2443992", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2443992", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Bleomycin is a highly effective antitumor agent, but pulmonary toxicity, characterized by an acute inflammatory reaction and associated pulmonary edema, limits clinical use of the drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1696541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "In this study we investigated bleomycin-induced pulmonary toxicity in patients with germ-cell tumour by means of technetium-99m diethylene triamine penta-acetic acid aerosol scintigraphy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7679991", "endSection": "abstract" } ] }, { "body": "What is another name for bimagrumab", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32690797" ], "ideal_answer": [ "Bimagrumab also goes by the name BYM338." ], "exact_answer": [ "BYM338" ], "type": "factoid", "id": "602c1b141cb411341a00011c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32690797", "endSection": "title" } ] }, { "body": "What is STATegra?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31672995" ], "ideal_answer": [ "STATegra is a comprehensive multi-omics dataset of B-cell differentiation in mouse. It includes measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation.", "It's a multi-omics dataset that combines measurements from up to 10 different omics technologies, namely pre-B-cell differentiation.", "Stategra is a multi-omics dataset that includes measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. It includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and is complemented with single-cell data.", "STATegra is a comprehensive multi-omics dataset of B-cell differentiation in mouse. It combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data." ], "type": "summary", "id": "6060e30a94d57fd87900004a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31672995", "endSection": "title" }, { "offsetInBeginSection": 646, "offsetInEndSection": 1146, "text": "Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31672995", "endSection": "abstract" } ] }, { "body": "What is the generic name of the Xofluza?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32601915", "http://www.ncbi.nlm.nih.gov/pubmed/30852344", "http://www.ncbi.nlm.nih.gov/pubmed/29623652", "http://www.ncbi.nlm.nih.gov/pubmed/33497124", "http://www.ncbi.nlm.nih.gov/pubmed/30766008", "http://www.ncbi.nlm.nih.gov/pubmed/30710642", "http://www.ncbi.nlm.nih.gov/pubmed/30983160", "http://www.ncbi.nlm.nih.gov/pubmed/34348638" ], "ideal_answer": [ "Baloxavir marboxi is the generic name of Xofluza. It is approved for influenza." ], "exact_answer": [ "Baloxavir marboxi" ], "type": "factoid", "id": "6023501a1cb411341a000096", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "Baloxavir marboxil (Xofluza\u00ae; hereafter referred to as baloxavir), the prodrug of baloxavir acid, is a first-in-class, small molecule inhibitor of the polymerase acidic (PA) protein subunit of the influenza virus polymerase complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32601915", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 446, "text": "Xofluza (baloxavir marboxil) for influenza approved in Japan under the SAKIGAKE Designation System is a good example of clinical trials including Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30710642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Arikayce (amikacin liposome inhalation suspension) for Mycobacterium avium complex lung disease; Xofluza (baloxavir marboxil) for acute uncomplicated influenza; and Nuzyra (omadacycline) for community-acquired bacterial pneumonia and/or acute bacterial skin and skin structure infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30766008", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 287, "text": "The latest approved antiviral is baloxavir marboxil (trade name, Xofluza) which targets the endonuclease function of the viral PA polymerase subunit and prevents the transcription of viral mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30852344", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 542, "text": "Baloxavir marboxil (Xofluza\u00ae), recently approved for clinical use, inhibits cap-snatching endonuclease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30983160", "endSection": "abstract" }, { "offsetInBeginSection": 92, "offsetInEndSection": 286, "text": "The latest approved antiviral is baloxavir marboxil (trade name, Xofluza) which targets the endonuclease function of the viral PA polymerase subunit and prevents the transcription of viral mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30852344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Baloxavir marboxil (Xofluza\u00ae; hereafter referred to as baloxavir), the prodrug of baloxavir acid, is a first-in-class, small molecule inhibitor of the polymerase acidic (PA) protein subunit of the influenza virus polymerase complex. Bal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32601915", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 289, "text": "he latest approved antiviral is baloxavir marboxil (trade name, Xofluza) which targets the endonuclease function of the viral PA polymerase subunit and prevents the transcription of viral mRNA. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30852344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Baloxavir marboxil (Xofluza\u2122; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29623652", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 864, "text": "se, from the innovation of to begin with antiviral medicate Idoxuridine in 1962 to the revelation of Baloxavir marboxil (Xofluza) that was FDA-approved in 2018, the hone of creating antivirals has changed significantly. In this art", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34348638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Arikayce (amikacin liposome inhalation suspension) for Mycobacterium avium complex lung disease; Xofluza (baloxavir marboxil) for acute uncomplicated influenza; and Nuzyra (omadacycline) for community-acquired bacterial pneumonia and/or acute bacterial skin and skin struc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30766008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Baloxavir marboxil (Xofluza), an antiviral flu treatment, has now been approved to prevent influenza.Pa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33497124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Baloxavir marboxil (Xofluza), an antiviral flu treatment, has now been approved to prevent influenza.Patients should avoid taking calcium, aluminum, or magnesium products while receiving baloxavir as this will lead to a loss of antiviral efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33497124", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 852, "text": "In any case, from the innovation of to begin with antiviral medicate Idoxuridine in 1962 to the revelation of Baloxavir marboxil (Xofluza) that was FDA-approved in 2018, the hone of creating antivirals has changed significantly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34348638", "endSection": "abstract" } ] }, { "body": "Is Keutel syndrome a common genetic disorder?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23917590", "http://www.ncbi.nlm.nih.gov/pubmed/23857752", "http://www.ncbi.nlm.nih.gov/pubmed/32821457" ], "ideal_answer": [ "No, Keutel syndrome (OMIM 245150) is a very rare syndrome" ], "exact_answer": "no", "type": "yesno", "id": "6082f4374e6a4cf63000000f", "snippets": [ { "offsetInBeginSection": 88, "offsetInEndSection": 142, "text": "Keutel syndrome (OMIM 245150) is a very rare syndrome ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32821457", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 118, "text": "Keutel syndrome is a rare autosomal-recessive condition characterized by abnormal cartilage calcification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23917590", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 217, "text": "MGP-deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23857752", "endSection": "abstract" } ] }, { "body": "Is fusobacterium associated with Lemierre's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11399017", "http://www.ncbi.nlm.nih.gov/pubmed/32257727", "http://www.ncbi.nlm.nih.gov/pubmed/25560619", "http://www.ncbi.nlm.nih.gov/pubmed/28736715", "http://www.ncbi.nlm.nih.gov/pubmed/23573433", "http://www.ncbi.nlm.nih.gov/pubmed/30648745", "http://www.ncbi.nlm.nih.gov/pubmed/20181152", "http://www.ncbi.nlm.nih.gov/pubmed/31211045", "http://www.ncbi.nlm.nih.gov/pubmed/15777309", "http://www.ncbi.nlm.nih.gov/pubmed/2649965", "http://www.ncbi.nlm.nih.gov/pubmed/30700448", "http://www.ncbi.nlm.nih.gov/pubmed/32455086", "http://www.ncbi.nlm.nih.gov/pubmed/32371121", "http://www.ncbi.nlm.nih.gov/pubmed/18330604", "http://www.ncbi.nlm.nih.gov/pubmed/30775398", "http://www.ncbi.nlm.nih.gov/pubmed/34235050", "http://www.ncbi.nlm.nih.gov/pubmed/14595080", "http://www.ncbi.nlm.nih.gov/pubmed/20954654", "http://www.ncbi.nlm.nih.gov/pubmed/21546562", "http://www.ncbi.nlm.nih.gov/pubmed/24942004", "http://www.ncbi.nlm.nih.gov/pubmed/22668650", "http://www.ncbi.nlm.nih.gov/pubmed/25431696", "http://www.ncbi.nlm.nih.gov/pubmed/17934077", "http://www.ncbi.nlm.nih.gov/pubmed/32257468", "http://www.ncbi.nlm.nih.gov/pubmed/18552584", "http://www.ncbi.nlm.nih.gov/pubmed/27693542", "http://www.ncbi.nlm.nih.gov/pubmed/16516355", "http://www.ncbi.nlm.nih.gov/pubmed/29796209", "http://www.ncbi.nlm.nih.gov/pubmed/22464641", "http://www.ncbi.nlm.nih.gov/pubmed/34758377", "http://www.ncbi.nlm.nih.gov/pubmed/20163040", "http://www.ncbi.nlm.nih.gov/pubmed/32742883", "http://www.ncbi.nlm.nih.gov/pubmed/31843654", "http://www.ncbi.nlm.nih.gov/pubmed/26793462", "http://www.ncbi.nlm.nih.gov/pubmed/26117393", "http://www.ncbi.nlm.nih.gov/pubmed/22633566", "http://www.ncbi.nlm.nih.gov/pubmed/8784713" ], "ideal_answer": [ "Lemierre's syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum.", "Yes. Lemierre's syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum.", "Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum", "Lemierre's syndrome is a rare condition that results from oropharyngeal infection, usually with the gram-negative, anaerobic Fusobacterium necrophorum." ], "exact_answer": "yes", "type": "yesno", "id": "601d724a1cb411341a000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Invasive infections with Fusobacterium necrophorum including Lemierre's syndrome: an 8-year Swedish nationwide retrospective study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31843654", "endSection": "title" }, { "offsetInBeginSection": 14, "offsetInEndSection": 108, "text": "Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32371121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Lemierre's syndrome is a rare but life-threatening condition characterized by an oropharyngeal infection typically secondary to Fusobacterium necrophorum resulting in septic thrombophlebitis of the internal jugular vein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32455086", "endSection": "abstract" }, { "offsetInBeginSection": 36, "offsetInEndSection": 179, "text": " Lemierre's syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32257468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemierre's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16516355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "[Lemierre syndrome variant: Hepatic abscesses and hepatic venous thrombosis due to Fusobacterium nucleatum septicemia].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16516355", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Fusobacterium necrophorum-induced sepsis: an unusual case of Lemierre's syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15777309", "endSection": "title" }, { "offsetInBeginSection": 296, "offsetInEndSection": 419, "text": "F necrophorum is most commonly associated with Lemierre's syndrome: a septic thrombophlebitis of the internal jugular vein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Fusobacterium necrophorum Septicemia Leading to Lemierre's Syndrome in an Immunocompetent Individual: A Case Report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32257727", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "We present a case of a patient with Lemierre's syndrome caused by Fusobacterium necrophorum who developed a right frontal lobe brain abscess.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Lemierre's syndrome secondary to Fusobacterium necrophorum infection, a rare cause of hepatic abscess.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20163040", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Lemierre's syndrome is an uncommon complication of pharyngitis commonly associated with an anaerobic gram negative bacterium, Fusobacterium necrophorum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23573433", "endSection": "abstract" }, { "offsetInBeginSection": 445, "offsetInEndSection": 600, "text": "The following presentation is a case of Lemierre's syndrome in a 23-year-old healthy individual who is infected by a rare species: Fusobacterium nucleatum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23573433", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 271, "text": "However, Fusobacterium species causing Lemierre's variant gastrointestinal syndrome has only been reported in case reports.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32742883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Fusobacterium species is known for being a causative agent for Lemierre's syndrome, which is characterized by thrombophlebitis of the jugular vein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32742883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The Fusobacterium species is known for its association with septic thrombophlebitis of the internal jugular vein (Lemierre's syndrome). Lemierre's syndrome is as", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30775398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Lemierre's syndrome due to Fusobacterium necrophorum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22633566", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Fusobacterium species are well described as the causative pathogen in Lemierre's syndrome, a suppurative thrombophlebitis of the jugular vein. However, they are less r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Introduction: Lemierre's syndrome is a rare but serious complication of an oral infection mostly related to Fusobacterium necrophorum. This condition combines j", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34235050", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27693542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "INTRODUCTION: Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum, associated with septic thrombophlebitis of the internal ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32371121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Fusobacterium nucleatum is a gram-negative bacillius commonly found in oropharynx and is traditionally associated with Lemierre syndrome, which is characterized by history of recent oropharyngeal infection, internal jugular vein thrombosis, and isolation of anaerobic pathogens, mainly Fuosobacterium necrophorum. Ho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24942004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Lemierre's syndrome is an uncommon complication of pharyngitis commonly associated with an anaerobic gram negative bacterium, Fusobacterium necrophorum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23573433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Fusobacterium species is known for being a causative agent for Lemierre's syndrome, which is characterized by thrombophlebitis of the jugular vein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32742883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Lemierre's syndrome is a systemic complication commonly caused by oropharyngeal infection by Fusobacterium species, which manifests itself as an internal jugular vein thrombosis formation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29796209", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Lemierre's syndrome is a rare but serious condition, characterized by disseminated infection with Fusobacterium necrophorum, most often originating from the oropharynx. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22668650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Lemierre's syndrome is a rare clinical condition that generally develops secondary to oropharyngeal infection caused by Fusobacterium necrophorum, which is an anaerobic bacteria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25431696", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "Lemierre's syndrome, a systemic anaerobic infection caused by Fusobacterium necrophorum, is characterized by an acute oropharyngeal infection, septic thrombophlebitis of the internal jugular veins, sepsis, and multiple metastatic infections. It c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11399017", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Lemierre's syndrome, a systemic anaerobic infection caused by Fusobacterium necrophorum, is characterized by an acute oropharyngeal infection, septic thrombophlebitis of the internal jugular vein, sepsis, and multiple metastatic infections. It c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8784713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Fusobacterium necrophorum is a rare infection most notable for causing Lemierre's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30700448", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "We present a patient with an atypical presentation of Fusobacterium infection, the genus responsible for Lemierre's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21546562", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemier", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16516355", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 205, "text": "Fusobacterium necrophorum, a well\u2010known cause of Lemierre's syndrome, was identified.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30648745", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "We report an unusual case of Lemierre's syndrome due to a rare species of Fusobacterium, that is,\u00a0Fusobacterium nucleatum preceded by Mycoplasma pneumoniae pharyngitis and followed later by\u00a0Epstein-Barr virus infectious mononucleosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22464641", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 495, "text": "We present a case of invasive Fusobacterium infection that meets all criteria for Lemierre syndrome except lacking internal jugular thrombosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25560619", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 399, "text": "Fusobacterium necrophorum is ananaerobic Gram-negative bacillus and is the most common organism reported to cause Lemierre's syndrome which usually occurs one to three weeks post pharyngitis or oropharyngeal surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26117393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Lemierre's disease: postanginal bacteremia and pulmonary involvement caused by Fusobacterium necrophorum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2649965", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Increased diagnosis of Lemierre syndrome and other Fusobacterium necrophorum infections at a Children's Hospital.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14595080", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The Fusobacterium species is known for its association with septic thrombophlebitis of the internal jugular vein (Lemierre's syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30775398", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 311, "text": "Fusobacterium species have rarely been implicated in cases of gastrointestinal variant of Lemierre's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26793462", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Fusobacterium species are well described as the causative pathogen in Lemierre's syndrome, a suppurative thrombophlebitis of the jugular vein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28736715", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 784, "text": "F. necrophorum is unique among non-spore-forming anaerobes, first for its virulence and association with Lemierre's syndrome as a monomicrobial infection and second because it seems probable that it is an exogenously acquired infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17934077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Fusobacteria are most often associated with the classic presentation of Lemierre's syndrome consisting of a sore throat, internal jugular vein thrombophlebitis, and septic emboli to the lungs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18552584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Fusobacterium necrophorum plays a causal role in a rare and life-threatening condition, Lemierre's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31211045", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Lemierre's syndrome is a rare disorder of young adults caused by the anaerobic bacterium, Fusobacterium necrophorum and occasionally by other Fusobacterium species (F. nucleatum, F. mortiferum and F. varium etc).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20181152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Lemierre's syndrome is a severe complication of Fusobacterium necrophorum oropharyngeal infection associated with metastatic foci of infection, internal jugular vein thrombosis, and septicemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20954654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Short blood culture time-to-positivity in Fusobacterium necrophorum bacteremia is associated with Lemierre's syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34758377", "endSection": "title" }, { "offsetInBeginSection": 165, "offsetInEndSection": 261, "text": "The causative organisms are the anaerobic fusobacteria, most commonly Fusobacterium necrophorum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15777309", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "In a 3-year prospective study, all cases of disseminated Fusobacterium necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the aim of describing the epidemiology and clinical features of the variants of Lemierre's syndrome and disseminated non-head-and-neck-associated F. necrophorum infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18330604", "endSection": "abstract" } ] }, { "body": "What is the synonym of MK-1602?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31758661" ], "ideal_answer": [ "MK-1602 is also named Ubrogepant." ], "exact_answer": [ "ubrogepant" ], "type": "factoid", "id": "6026d8641cb411341a0000cd", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758661", "endSection": "abstract" } ] }, { "body": "How many families did the 100,000 Genomes Pilot enrol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34758253" ], "ideal_answer": [ "The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. A pilot study was conducted involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present.", "The 100,000 Genomes Project is a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present." ], "exact_answer": [ "2183" ], "type": "factoid", "id": "61f919cc882a024a10000048", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 511, "text": "The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection.METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34758253", "endSection": "abstract" } ] }, { "body": "What is CIS43LS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34379916", "http://www.ncbi.nlm.nih.gov/pubmed/34511592", "http://www.ncbi.nlm.nih.gov/pubmed/33332286" ], "ideal_answer": [ "CIS43LS is an antimalarial monoclonal antibody with an extended half-life against infection with Plasmodium falciparum." ], "type": "summary", "id": "61f5ffc8882a024a1000001d", "snippets": [ { "offsetInBeginSection": 976, "offsetInEndSection": 1181, "text": ". On August 26, 2021, the findings from a phase 1 trial on a new monoclonal antibody to PfCSP, CIS43LS, showed that a single dose of the CIS43LS monoclonal antibody resulted in protection against malaria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34511592", "endSection": "abstract" }, { "offsetInBeginSection": 1150, "offsetInEndSection": 1306, "text": "Based on these data, CIS43LS has advanced to phase I clinical trials, and AAV delivery provides a potential next-generation approach for malaria prevention.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33332286", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 342, "text": "METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34379916", "endSection": "abstract" }, { "offsetInBeginSection": 1910, "offsetInEndSection": 2095, "text": "CONCLUSIONS: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34379916", "endSection": "abstract" }, { "offsetInBeginSection": 1968, "offsetInEndSection": 2153, "text": "ion or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34379916", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1205, "text": "e findings from a phase 1 trial on a new monoclonal antibody to PfCSP, CIS43LS, showed that a single dose of the CIS43LS monoclonal antibody resulted in protection against malaria. These new findings have ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34511592", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 321, "text": "by malaria.METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Pl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34379916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "BACKGROUND: Additional interventions are needed to reduce the morbidity and mortality caused by malaria.METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34379916", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1180, "text": "On August 26, 2021, the findings from a phase 1 trial on a new monoclonal antibody to PfCSP, CIS43LS, showed that a single dose of the CIS43LS monoclonal antibody resulted in protection against malaria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34511592", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 2052, "text": "lled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 \u03bcg per milliliter at the time of controlled human malaria infection.CONCLUSIONS: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34379916", "endSection": "abstract" } ] }, { "body": "List the main salt-inducible kinases.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33688765", "http://www.ncbi.nlm.nih.gov/pubmed/33989615", "http://www.ncbi.nlm.nih.gov/pubmed/34350957", "http://www.ncbi.nlm.nih.gov/pubmed/34196217", "http://www.ncbi.nlm.nih.gov/pubmed/33148508", "http://www.ncbi.nlm.nih.gov/pubmed/34056256", "http://www.ncbi.nlm.nih.gov/pubmed/33861845" ], "ideal_answer": [ "SIK1\nSIK2\nSIK3\nHDAC4\nHDAC5" ], "exact_answer": [ [ "SIK1" ], [ "SIK2" ], [ "SIK3" ], [ "HDAC4" ], [ "HDAC5" ] ], "type": "list", "id": "621b806c3a8413c653000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "PTHrP targets salt-inducible kinases, HDAC4 and HDAC5,", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33148508", "endSection": "title" }, { "offsetInBeginSection": 372, "offsetInEndSection": 563, "text": ". SIKs (salt-inducible kinases) are a subfamily of the AMP-activated protein kinase family that play a critical role in metabolic diseases including hepatic lipogenesis and glucose metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34196217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "Salt-inducible kinases (SIKs) represent a subfamily of AMPK family kinases. SIK1 has been shown to act as a mediator during the cellular adaptation to variations in intracellular sodium in a variety of cell types. SIK2, as an isoform of the SIK family, modulates various biological functions and acts as a signal transmitter in various pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33688765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "Type 1 salt-inducible kinases (SIK1) has been shown to act as a mediator during the cellular adaptation to variations in intracellular sodium in a variety of cell types. Type 2 SIK (SIK2) modulates various biological functions and acts as a signal transmitter in various pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33989615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Salt-inducible kinases (SIKs) are calcium/calmodulin-dependent protein kinase (CAMK)-like (CAMKL) family members implicated in insulin signal transduction, metabolic regulation, inflammatory response, and other processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34056256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "The salt-inducible kinases, SIK1, SIK2 and SIK3, most closely resemble the AMP-activated protein kinase (AMPK) and other AMPK-related kinases, and like these family members they require phosphorylation by LKB1 to be catalytically active.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33861845", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 406, "text": "The first is the activation of the salt-inducible kinases (SIKs; SIK2 and SIK3) by Na+ stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34350957", "endSection": "abstract" } ] }, { "body": "Unlike DNA, RNA is not methylated, yes or no?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18567810", "http://www.ncbi.nlm.nih.gov/pubmed/34694621", "http://www.ncbi.nlm.nih.gov/pubmed/27375676", "http://www.ncbi.nlm.nih.gov/pubmed/4992370", "http://www.ncbi.nlm.nih.gov/pubmed/16424344", "http://www.ncbi.nlm.nih.gov/pubmed/19808971", "http://www.ncbi.nlm.nih.gov/pubmed/16111635", "http://www.ncbi.nlm.nih.gov/pubmed/33526437", "http://www.ncbi.nlm.nih.gov/pubmed/34694619", "http://www.ncbi.nlm.nih.gov/pubmed/28349450" ], "ideal_answer": [ "In addition to DNA methylation, reversible epigenetic modification occurring in RNA has been discovered recently. The most abundant type of RNA methylation is N6-methyladenosine (m6A) modification, which is dynamically regulated by methylases (\"writers\"), demethylases (\"erasers\") and m6A-binding proteins (\"readers\")", "N6-methyladenosine (m6A) is the most abundant internal modification on messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in eukaryotes" ], "exact_answer": "no", "type": "yesno", "id": "621fd6083a8413c653000066", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Mapping the position and quantifying the level of 5-methylcytosine (m5C) as a modification in different types of cellular RNA is an important objective in the field of epitranscriptomics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34694621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "N6-methyladenosine (m6A) is the most abundant internal modification on messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in eukaryotes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34694619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33526437", "endSection": "title" }, { "offsetInBeginSection": 419, "offsetInEndSection": 603, "text": "nogaster was methylated to a lower degree, but in the case of Dictyostelium, there was no difference in the methylation of RNA isolated from wild-type and Dnmt2 knock-out strains. Meth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18567810", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "The detection and quantification of methylated RNA can be beneficial to understand certain cellular regulation processes such as transcriptional modulation of gene expression, immune response, or epigenetic alterations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28349450", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 420, "text": "ombined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNA(Asp)) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16424344", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 340, "text": "ted nucleosides in naturally occurring RNA are also methylated or otherwise modified, but the immunomodulatory effects of these alterations remain untested. We s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16111635", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1129, "text": "-induced loss of RNA methylation seemed specific for DNMT2 target sites because we did not observe any significant demethylation at sites known to be methylated by other RNA methyltransferases. Our results ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19808971", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 920, "text": "Crude extracts of this organism possess RNA methylase activity but no detectable DNA methylase activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4992370", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 416, "text": "A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNA(Asp)) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16424344", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 405, "text": "Here, we propose that RNA methylation began prior to DNA methylation in the early forms of life evolving on Earth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27375676", "endSection": "abstract" } ] }, { "body": "What methodology does the Oncomine Dx target test use?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31349061" ], "ideal_answer": [ "The Oncomine Dx target test uses the next generation sequencing methodology." ], "exact_answer": [ "next generation sequencing", "NGS" ], "type": "factoid", "id": "606bfeb494d57fd879000074", "snippets": [ { "offsetInBeginSection": 861, "offsetInEndSection": 992, "text": "FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31349061", "endSection": "abstract" } ] }, { "body": "Describe the application of whole genome sequencing in the diagnosis of primary ciliary dyskinesia (PCD)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34556108" ], "ideal_answer": [ "Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants. In these cases it may detect SVs and is a powerful tool for novel gene discovery.", "Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. In these cases it may detect SVs and is a powerful tool for novel gene discovery. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants.", "WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants." ], "type": "summary", "id": "61f50f8b882a024a10000001", "snippets": [ { "offsetInBeginSection": 1837, "offsetInEndSection": 2138, "text": "Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants. In these cases it may detect SVs and is a powerful tool for novel gene discovery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34556108", "endSection": "abstract" } ] }, { "body": "Which CD38 antibody has been shown to be effective for Lupus Erythematosus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33828555", "http://www.ncbi.nlm.nih.gov/pubmed/32937047", "http://www.ncbi.nlm.nih.gov/pubmed/29720240" ], "ideal_answer": [ "Daratumumab, a human monoclonal antibody that targets CD38, has been used to treat Lupus Erythematosus." ], "exact_answer": [ "Daratumumab" ], "type": "factoid", "id": "6020a8431cb411341a00007f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32937047", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 564, "text": "Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32937047", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 340, "text": "This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29720240", "endSection": "abstract" }, { "offsetInBeginSection": 1707, "offsetInEndSection": 1890, "text": "CONCLUSION: These results indicate that CD38 may be a potential target for RA disease interception and daratumumab should be evaluated clinically for the treatment of both RA and SLE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29720240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32937047", "endSection": "title" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1162, "text": "addition, ligation of SLAMF7 with elotuzumab or of CD38 with daratumumab on SLE NK cells enhanced degranulation of both healthy and SLE NK cells and primed them to kill circulating plasma cells in an in vitro co-culture ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33828555", "endSection": "abstract" }, { "offsetInBeginSection": 939, "offsetInEndSection": 1169, "text": "In addition, ligation of SLAMF7 with elotuzumab or of CD38 with daratumumab on SLE NK cells enhanced degranulation of both healthy and SLE NK cells and primed them to kill circulating plasma cells in an in vitro co-culture system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33828555", "endSection": "abstract" }, { "offsetInBeginSection": 1489, "offsetInEndSection": 1848, "text": " from patients with early RA. Most importantly, our data show for the first time that daratumumab effectively depletes plasma cells/plasmablasts in PBMC from patients with SLE and RA in a dose-dependent manner ex vivo.CONCLUSION: These results indicate that CD38 may be a potential target for RA disease interception and daratumumab should be evaluated clinic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29720240", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 1091, "text": "osus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE.METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target.RESULTS: We demonstrated that the plasma cell/plasmablast-related genes CD38, XBP1, IRF4, PRDM1, IGJ and TNFSF13B are significantly up-regulated in synovial biopsies from patients with arthralgia, undifferentiated arthritis (UA), early RA and established RA as compared to healthy controls and control", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29720240", "endSection": "abstract" } ] }, { "body": "What is a circRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32667692", "http://www.ncbi.nlm.nih.gov/pubmed/32889059", "http://www.ncbi.nlm.nih.gov/pubmed/33112505" ], "ideal_answer": [ "Circular RNAs (circRNAs) are a new class of non-coding RNA with a stable structure formed by special loop splicing." ], "exact_answer": [ "Circular RNAs (circRNAs) are a new class of non-coding RNA with a stable structure formed by special loop splicing." ], "type": "factoid", "id": "60853db94e6a4cf630000010", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 127, "text": "Circular RNAs (circRNAs) are a new class of non-coding RNA with a stable structure formed by special loop splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32889059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Circular RNAs (circRNA) have been reported as regulators involved in hepatocellular carcinoma (HCC), but their mechanism of activity remains unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32667692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 472, "text": "Recent technological advances in RNA sequencing and analysis have allowed an increasingly thorough investigation of a previously unexplored class of transcripts, circular (circ)RNAs. Accumulating evidence suggests that circRNAs have unique functions which often rely on their association with microRNAs and RNA-binding proteins. Through these interactions, circRNAs have been implicated in major cellular processes and hence in the pathophysiology of a range of diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33112505", "endSection": "abstract" } ] }, { "body": "Summarize Fanconi's anemia", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/7240694", "http://www.ncbi.nlm.nih.gov/pubmed/34585473", "http://www.ncbi.nlm.nih.gov/pubmed/1574115", "http://www.ncbi.nlm.nih.gov/pubmed/25332625", "http://www.ncbi.nlm.nih.gov/pubmed/1530123", "http://www.ncbi.nlm.nih.gov/pubmed/12483114", "http://www.ncbi.nlm.nih.gov/pubmed/34735020", "http://www.ncbi.nlm.nih.gov/pubmed/33977503", "http://www.ncbi.nlm.nih.gov/pubmed/31281162", "http://www.ncbi.nlm.nih.gov/pubmed/31390058", "http://www.ncbi.nlm.nih.gov/pubmed/11524917", "http://www.ncbi.nlm.nih.gov/pubmed/21331524", "http://www.ncbi.nlm.nih.gov/pubmed/16188650", "http://www.ncbi.nlm.nih.gov/pubmed/11759873", "http://www.ncbi.nlm.nih.gov/pubmed/15643609", "http://www.ncbi.nlm.nih.gov/pubmed/28657246", "http://www.ncbi.nlm.nih.gov/pubmed/19427003", "http://www.ncbi.nlm.nih.gov/pubmed/19728769", "http://www.ncbi.nlm.nih.gov/pubmed/12053693" ], "ideal_answer": [ "Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer." ], "type": "summary", "id": "62211b5a3a8413c65300006b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Fanconi anemia (FA) is a multisystem disease, characterized by the triad of physical abnormalities, bone marrow failure, and increased risk for malignancy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33977503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Fanconi anemia is a rare disorder resulting from defects in genes responsible for DNA damage responses. It is characterized by congenital anomalies, aplastic anemia, and a predisposition to cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34735020", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Fanconi anemia (FA) is a rare inherited genetic condition that may lead to bone marrow failure, leukemia, and/or solid tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31390058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Fanconi's Anaemia is a rare autosomal recessive disease for which the incidence of head and neck cancer can be increased 700-fold1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28657246", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Fanconi's Anemia is primarily an autosomal recessive genetic disorder characterized by congenital abnormalities, defective haematopoiesis leading to bone marrow failure and increased risk of development of Myelodysplastic syndrome, acute myeloid leukemia and solid tumours", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25332625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Fanconi's anemia is a rare autosomal recessive disorder associated with variable clinical manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12053693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Fanconi's anemia, an inherited disorder characterized by bone marrow aplasia, peripheral pancytopenia, and multiple congenital defects, has a association with certain types of malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7240694", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19427003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Fanconi anemia is a genetically heterogeneous disorder associated with chromosome instability and a highly elevated risk for developing cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728769", "endSection": "abstract" }, { "offsetInBeginSection": 239, "offsetInEndSection": 433, "text": "Fanconi anemia proteins are extensively connected with DNA caretaker proteins, and appear to function as a hub for the coordination of DNA repair with DNA replication and cell cycle progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19728769", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Fanconi's anaemia is a rare autosomal recessive disorder characterized by progressive pancytopaenia and a cellular hypersensitivity to DNA crosslinking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1574115", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Fanconi's anemia is an autosomal recessive disorder with a high incidence (greater than 90%) of aplastic anemia and a premalignant component with a greater than 10% risk of leukemia or solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1530123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "BACKGROUND: Fanconi's anemia is an autosomal recessive disease associated with chromosomal breakage as well as pancytopenia, skin pigmentation, renal hypoplasia, cardiac defects, microcephaly, congenital malformations of the skeleton, hypogonadism, and increased risk ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11759873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Fanconi's anemia is a rare autosomal recessive disease characterized by congenital abnormalities, a progressive pancytopenia and a predisposition to cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11524917", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder, characterized by congenital anomalies, defective hematopoiesis and a high risk of developing acute myeloid leukemia and certain solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16188650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Fanconi anemia (FA) is a cancer predisposition disorder characterized by progressive bone marrow failure, congenital developmental defects, chromosomal abnormalities, and cellular hypersensitivity to DNA interstrand crosslink (ICL) agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21331524", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by multiple congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancies, resulting from mutations in one of the 22 known FANC genes (from FANCA to FANCW).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31281162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Fanconi anemia (FA) is an autosomal recessive disorder that is defined by cellular hypersensitivity to DNA cross-linking agents, and is characterized clinically by developmental abnormalities, progressive bone-marrow failure, and predisposition to leukemia and solid tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15643609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Fanconi anemia is a rare autosomal recessive disease characterized by bone marrow failure, developmental anomalies, a high incidence of myelodysplasia and acute nonlymphocytic leukemia, and cellular hypersensitivity to cross linking agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12483114", "endSection": "abstract" } ] }, { "body": "Which one of the CYP450 enzymes is the second most frequently implicated in the metabolism of the drugs currently available on the market?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32786546" ], "ideal_answer": [ "CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% of the drugs on the market, respectively." ], "exact_answer": [ "CYP2D6" ], "type": "factoid", "id": "6211454a3a8413c65300000b", "snippets": [ { "offsetInBeginSection": 290, "offsetInEndSection": 430, "text": "Among CYP enzymes, CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% of the drugs on the market, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32786546", "endSection": "abstract" } ] }, { "body": "Describe SBGNview", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34864890" ], "ideal_answer": [ "SBGNview is a tool set for pathway based data visalization", "Pathway analysis is widely used in genomics and omics research, but the data visualization has been highly limited in function, pathway coverage and data format. SBGNview is a comprehensive R package to address these needs." ], "type": "summary", "id": "62190f633a8413c653000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "SBGNview: towards data analysis, integration and visualization on all pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864890", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 247, "text": "Pathway analysis is widely used in genomics and omics research, but the data visualization has been highly limited in function, pathway coverage and data format. Here, we develop SBGNview a comprehensive R package to address these needs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864890", "endSection": "abstract" } ] }, { "body": "Which diseases can be treated with Itepekimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "http://www.ncbi.nlm.nih.gov/pubmed/34706171", "http://www.ncbi.nlm.nih.gov/pubmed/34523807" ], "ideal_answer": [ "Itepekimab, a monoclonal antibody targeting IL-33, demonstrated clinical activity in asthma, with potential in chronic obstructive pulmonary disease (COPD)." ], "exact_answer": [ [ "asthma" ], [ "chronic obstructive pulmonary disease" ] ], "type": "list", "id": "61f5f1ef882a024a10000015", "snippets": [ { "offsetInBeginSection": 67, "offsetInEndSection": 224, "text": "Itepekimab, a monoclonal antibody targeting IL-33, demonstrated clinical activity in asthma, with potential in chronic obstructive pulmonary disease (COPD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 668, "text": "On the basis of the strong association of IL-33 pathway genes with pulmonary diseases like asthma and COPD, we conducted this phase 2a trial to assess the safety and efficacy of itepekimab in patients with moderate-to-severe COPD on a stable regimen of triple-inhaled or double-inhaled background maintenance therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "title" }, { "offsetInBeginSection": 3518, "offsetInEndSection": 3716, "text": "INTERPRETATION: The primary endpoint in the overall population was not met, subgroup analysis showed that itepekimab reduced exacerbation rate and improved lung function in former smokers with COPD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706171", "endSection": "title" }, { "offsetInBeginSection": 2154, "offsetInEndSection": 2362, "text": "CONCLUSIONS: Interleukin-33 blockade with itepekimab led to a lower incidence of events indicating a loss of asthma control than placebo and improved lung function in patients with moderate-to-severe asthma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706171", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34523807", "endSection": "title" }, { "offsetInBeginSection": 67, "offsetInEndSection": 223, "text": "Itepekimab, a monoclonal antibody targeting IL-33, demonstrated clinical activity in asthma, with potential in chronic obstructive pulmonary disease (COPD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 214, "text": "ptibility. Itepekimab, a monoclonal antibody targeting IL-33, demonstrated clinical activity in asthma, with potential in chronic obstructive pulmonary diseas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706171", "endSection": "title" }, { "offsetInBeginSection": 1896, "offsetInEndSection": 2054, "text": "with the combination therapy. Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706171", "endSection": "abstract" }, { "offsetInBeginSection": 2614, "offsetInEndSection": 2915, "text": " [95% CI 0\u00b701-0\u00b710], p=0\u00b7024). When analysis was restricted to former smokers, treatment with itepekimab was associated with nominally significant reductions in acute exacerbations of COPD (RR 0\u00b758 [95% CI 0\u00b739-0\u00b785], p=0\u00b70061) and FEV1 improvement (least squares mean difference 0\u00b709 L [0\u00b702-0\u00b715], p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "abstract" }, { "offsetInBeginSection": 848, "offsetInEndSection": 1027, "text": "racterised for COPD. We then did a double-blind, phase 2a trial comparing itepekimab with placebo in patients with moderate-to-severe COPD despite standard therapy, at 83 study si", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302758", "endSection": "abstract" } ] }, { "body": "What is the msDNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16093702", "http://www.ncbi.nlm.nih.gov/pubmed/29087272", "http://www.ncbi.nlm.nih.gov/pubmed/11525386", "http://www.ncbi.nlm.nih.gov/pubmed/22102774", "http://www.ncbi.nlm.nih.gov/pubmed/15459648" ], "ideal_answer": [ "msDNA is actually a complex of DNA, RNA, and probably protein. It is composed of a small, single-stranded DNA, linked to a small, single-stranded RNA molecule. The 5' end of the DNA molecule is joined to an internal guanosine residue of the RNA molecule by a unique 2'-5' phosphodiester bond. msDNA is produced in many hundreds of copies per cell, but its function remains unknown." ], "exact_answer": [ "msDNA is actually a complex of DNA, RNA, and probably protein." ], "type": "factoid", "id": "603534671cb411341a000153", "snippets": [ { "offsetInBeginSection": 355, "offsetInEndSection": 738, "text": " msDNA is actually a complex of DNA, RNA, and probably protein. It is composed of a small, single-stranded DNA, linked to a small, single-stranded RNA molecule. The 5' end of the DNA molecule is joined to an internal guanosine residue of the RNA molecule by a unique 2'-5' phosphodiester bond. msDNA is produced in many hundreds of copies per cell, but its function remains unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16093702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Retron is a prokaryotic genetic element that produces multicopy single-stranded DNA covalently linked to RNA (msDNA) by a reverse transcriptase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15459648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "msDNAs are small, structurally unique satellite DNAs found in a number of Gram-negative bacteria. Composed of hundreds of copies of single-stranded DNA--hence the name multicopy single-stranded DNA--msDNA is actually a complex of DNA, RNA, and probably protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11525386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The multi-copy single-stranded DNA (msDNA) is yielded by the action of reverse transcriptase of retro-element in a wide range of pathogenic bacteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22102774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Multi-copy single-stranded DNA (msDNA) is composed of covalently bound single-stranded DNA and RNA, and synthesized by retron-encoded reverse transcriptase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29087272", "endSection": "abstract" } ] }, { "body": "Are Epoxyeicosatrienoic acids (EETs) synthesized by cytochrome P450 epoxygenases from arachidonic acid?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21742052", "http://www.ncbi.nlm.nih.gov/pubmed/1480136", "http://www.ncbi.nlm.nih.gov/pubmed/24040964", "http://www.ncbi.nlm.nih.gov/pubmed/24311719", "http://www.ncbi.nlm.nih.gov/pubmed/17150260", "http://www.ncbi.nlm.nih.gov/pubmed/22802958", "http://www.ncbi.nlm.nih.gov/pubmed/15026029", "http://www.ncbi.nlm.nih.gov/pubmed/28319086", "http://www.ncbi.nlm.nih.gov/pubmed/22009066", "http://www.ncbi.nlm.nih.gov/pubmed/24490654", "http://www.ncbi.nlm.nih.gov/pubmed/28937442", "http://www.ncbi.nlm.nih.gov/pubmed/27448715", "http://www.ncbi.nlm.nih.gov/pubmed/21040800", "http://www.ncbi.nlm.nih.gov/pubmed/16169934", "http://www.ncbi.nlm.nih.gov/pubmed/14636671", "http://www.ncbi.nlm.nih.gov/pubmed/16113065", "http://www.ncbi.nlm.nih.gov/pubmed/20950340", "http://www.ncbi.nlm.nih.gov/pubmed/16490839", "http://www.ncbi.nlm.nih.gov/pubmed/18812234", "http://www.ncbi.nlm.nih.gov/pubmed/27494529", "http://www.ncbi.nlm.nih.gov/pubmed/27166927", "http://www.ncbi.nlm.nih.gov/pubmed/29022765", "http://www.ncbi.nlm.nih.gov/pubmed/28328948", "http://www.ncbi.nlm.nih.gov/pubmed/10627503", "http://www.ncbi.nlm.nih.gov/pubmed/16380164" ], "ideal_answer": [ "Epoxyeicosatrienoic acids (EETs) are fatty acid signaling molecules synthesized by cytochrome P450 epoxygenases from arachidonic acid", "Yes. Epoxyeicosatrienoic acids (EETs) are synthesized by cytochrome P450 epoxygenases from arachidonic acid.", "Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells." ], "exact_answer": "yes", "type": "yesno", "id": "621ea5a53a8413c653000055", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Biologically active epoxyeicosatrienoic acid (EET) regioisomers are synthesized from arachidonic acid by cytochrome P450 epoxygenases of endothelial, myocardial, and renal tubular cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28937442", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 545, "text": "epoxyeicosatrienoic acids (EETs), synthesized by cytochrome P450 epoxygenases from arachidonic acid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24490654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 epoxygenases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22802958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14636671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10627503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20950340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to \u03c9-terminal hydroxyeicosatetraenoic acids (HETEs) by \u03c9-hydroxylases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28328948", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 epoxygenases, are converted to dihydroxyeicosatrienoic acids by soluble epoxide hydrolase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22802958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14636671", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 451, "text": "Epoxygenases metabolize arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs) and selected monohydroxyeicosatetraenoic acids (HETEs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24311719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Epoxyeicosatrienoic acids (EETs) are potent lipid mediators formed by cytochrome P450 epoxygenases from arachidonic acid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27166927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20950340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Epoxyeicosatrienoic acids (EETs), derived from arachidonic acid by cytochrome P450 epoxygenases, are potent vasodilators that function as endothelium-derived hyperpolarizing factors in some vascular beds. E", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17150260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14636671", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 276, "text": "poxyeicosatrienoic acids (EETs) are epoxy lipids derived from metabolism of arachidonic acid by cytochrome P450 epoxygenases. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27494529", "endSection": "abstract" }, { "offsetInBeginSection": 109, "offsetInEndSection": 231, "text": "he vascular endothelium metabolizes arachidonic acid by cytochrome P450 epoxygenases to epoxyeicosatrienoic acids or EETs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15026029", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28319086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "OBJECTIVE: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory pro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29022765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the cardiovascular system. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21742052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites produced by cytochrome P450 epoxygenases which are highly expressed in hepatocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21040800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Epoxyeicosatrienoic acids (EETs) are epoxides of arachidonic acid generated by cytochrome P450 (CYP) epoxygenases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16490839", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 613, "text": "Although eicosanoids, including prostaglandins and leukotrienes, are best known as products of arachidonic acid metabolism by cyclooxygenases and lipoxygenases, arachidonic acid is also a substrate for another enzymatic pathway, the cytochrome P450 (CYP) system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22009066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Epoxyeicosatrienoic acids (EETs), lipid mediators synthesized from arachidonic acid by cytochrome P-450 epoxygenases, are converted by soluble epoxide hydrolase (SEH) to the corresponding dihydroxyeicosatrienoic acids (DHETs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16113065", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18812234", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10627503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Epoxyeicosatrienoic acids (EETs) are potent lipid mediators formed by cytochrome P450 epoxygenases from arachidonic acid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27166927", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 394, "text": "Recent studies show that mouse epidermis expresses CYP2B19, a keratinocyte-specific epoxygenase that generates 11,12- and 14,15-epoxyeicosatrienoic (EET) acids from arachidonate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16169934", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Identification of rabbit cytochromes P450 2C1 and 2C2 as arachidonic acid epoxygenases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1480136", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Epoxyeicosatrienoic acids (EETs) are formed from arachidonic acid by the action of P450 epoxygenases (CYP2C and CYP2J).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27448715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Epoxyeicosatrienoic acids (EETs) are generated from arachidonic acid by cytochrome P450 (CYP) epoxygenases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16380164", "endSection": "abstract" } ] }, { "body": "What percentage of currently available drugs are metabolized by CYP3A4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32786546" ], "ideal_answer": [ "CYP3A4 metabolizes approximately 50% of the drugs available today on the market." ], "exact_answer": [ "50%" ], "type": "factoid", "id": "621142713a8413c65300000a", "snippets": [ { "offsetInBeginSection": 290, "offsetInEndSection": 431, "text": "Among CYP enzymes, CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% of the drugs on the market, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32786546", "endSection": "abstract" } ] }, { "body": "What is caused by bi-allelic loss-of-function variants in IPO8?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34010605" ], "ideal_answer": [ "Bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes.", "Importin, a member of the importin-\u03b2 protein family, is a protein that translocates cargo molecules, proteins, and ribonucleoprotein complexes into the nucleus in RanGTP-dependent manner. Bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm.", "Syndromic thoracic aortic aneurysm" ], "exact_answer": [ "A syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes" ], "type": "factoid", "id": "61f810a5882a024a1000003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A human importin-\u03b2-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34010605", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 574, "text": "Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-\u03b2 protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-\u03b2 signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34010605", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Evinacumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33295805", "http://www.ncbi.nlm.nih.gov/pubmed/31578082", "http://www.ncbi.nlm.nih.gov/pubmed/32813947", "http://www.ncbi.nlm.nih.gov/pubmed/34585515", "http://www.ncbi.nlm.nih.gov/pubmed/34713869", "http://www.ncbi.nlm.nih.gov/pubmed/32841138", "http://www.ncbi.nlm.nih.gov/pubmed/32492513", "http://www.ncbi.nlm.nih.gov/pubmed/34698927", "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "http://www.ncbi.nlm.nih.gov/pubmed/31843957", "http://www.ncbi.nlm.nih.gov/pubmed/34253139", "http://www.ncbi.nlm.nih.gov/pubmed/30011918", "http://www.ncbi.nlm.nih.gov/pubmed/32511037", "http://www.ncbi.nlm.nih.gov/pubmed/34327869", "http://www.ncbi.nlm.nih.gov/pubmed/33278127", "http://www.ncbi.nlm.nih.gov/pubmed/31242752" ], "ideal_answer": [ "Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) that has been shown to reduce low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia." ], "type": "summary", "id": "6023415b1cb411341a00008c", "snippets": [ { "offsetInBeginSection": 163, "offsetInEndSection": 475, "text": "Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab, monoclonal antibodies against cholesterol-regulating proprotein convertase subtilisin/kexin type 9 and angiopoietin-like protein 3, may provide more benefit. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31843957", "endSection": "abstract" }, { "offsetInBeginSection": 976, "offsetInEndSection": 1117, "text": "Moreover, regarding TG a monoclonal antibody called evinacumab and an antisense-oligonucleotide against ANGPTL3 showed effective TG-lowering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32492513", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1170, "text": "Multiple ANGPLT3 inhibitors (evinacumab, IONIS-ANGPTL3-LRx, ARO-ANG3) effectuate TG reductions up to 70% with concomitant potent reduction in all other apoB containing lipoprotein fractions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32511037", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 638, "text": "Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32813947", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1711, "text": "These include an antisense oligonucleotide against apoC-III (volanesorsen), a monoclonal antibody against angiopoietin-like protein-3 (evinacumab), and other agents currently in development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32841138", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "A randomized study investigating the safety, tolerability, and pharmacokinetics of evinacumab, an ANGPTL3 inhibitor, in healthy Japanese and Caucasian subjects.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "BACKGROUND AND AIMS: Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, reduced low-density lipoprotein cholesterol (LDL-C) significantly in a Phase 2 study of patients with homozygous familial hypercholesterolemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1193, "text": "Evinacumab, a novel monoclonal antibody against angiopoetin-like 3 (ANGPTL3), reduces LDL-C by 50% independent of LDLR activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33278127", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 814, "text": "Modifications included the addition of intermediate-density lipoprotein and low-density lipoprotein compartments to address the modulation of lipoprotein lipase (LPL) activity by evinacumab, ANGPTL3 biosynthesis and clearance, and a target-mediated drug disposition model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34327869", "endSection": "abstract" }, { "offsetInBeginSection": 1378, "offsetInEndSection": 1577, "text": "nversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its LDLR-independent mechanism of action. M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34698927", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "A model to quantitatively characterize the effect of evinacumab, an investigational monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) on lipid trafficking is needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34327869", "endSection": "abstract" }, { "offsetInBeginSection": 246, "offsetInEndSection": 391, "text": "lipids. Evinacumab, an ANGPTL3 inhibitor, reduced triglycerides in healthy human volunteers and in homozygous familial hypercholesterolemic indiv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31242752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585515", "endSection": "abstract" }, { "offsetInBeginSection": 491, "offsetInEndSection": 629, "text": " disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholest", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32813947", "endSection": "abstract" }, { "offsetInBeginSection": 642, "offsetInEndSection": 774, "text": "ry atherosclerosis. Evinacumab, a fully human monoclonal antibody, inhibits ANGPTL3 and reduces multiple lipoprotein fractions ~50%,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34253139", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 943, "text": "e I clinical trials with a monoclonal anti-ANGPTL3 antibody (evinacumab) and anti-sense oligonucleotide (ASO) clearly show a significant lipid lowering effect. In addition, from t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30011918", "endSection": "abstract" }, { "offsetInBeginSection": 1598, "offsetInEndSection": 1861, "text": "er306Leu). Evinacumab had no effect on LDLR activity.CONCLUSIONS: These results suggest that evinacumab is effective for lowering LDL-C in patients with homozygous familial hypercholesterolemia, and the inhibition of ANGPTL3 in humans lowers LDL-C in a mechanism ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31578082", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 756, "text": "Evinacumab is a human monoclonal antibody which binds and inhibits angiopoietin-like protein 3 (ANGPTL3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34713869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585515", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 386, "text": "her lipids. Evinacumab, an ANGPTL3 inhibitor, reduced triglycerides in healthy human volunteers and in homozygous familial hypercholesterolemic ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31242752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "BACKGROUND AND AIMS: Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, reduced low-density lipoprotein cholesterol (LDL-C) significantly in a Phase 2 study of patients with homozygous familial ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130482", "endSection": "abstract" }, { "offsetInBeginSection": 489, "offsetInEndSection": 949, "text": "ar disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia.METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) ever", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32813947", "endSection": "abstract" }, { "offsetInBeginSection": 1340, "offsetInEndSection": 1539, "text": "n HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its L", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34698927", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 791, "text": "Evinacumab, a fully human monoclonal antibody, inhibits ANGPTL3 and reduces multiple lipoprotein fractions ~50%, including LDL-C.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34253139", "endSection": "abstract" }, { "offsetInBeginSection": 496, "offsetInEndSection": 589, "text": "Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like protein 3 (ANGPTL3).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33295805", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 620, "text": "r disease. A phase 2, proof-of-concept study (NCT02265952) demonstrated that evinacumab, a fully human monoclonal antibody to ANGPTL3 (angiopoietin-like 3 protein), reduced LDL-C levels in 9 patients with genotypically confirmed homozygous familial hypercholesterolemia and was well", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31578082", "endSection": "abstract" } ] }, { "body": "Which glands in the bee secretes royal jelly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30272666", "http://www.ncbi.nlm.nih.gov/pubmed/26083737", "http://www.ncbi.nlm.nih.gov/pubmed/31410279", "http://www.ncbi.nlm.nih.gov/pubmed/30953617" ], "ideal_answer": [ "hypopharyngeal glands" ], "exact_answer": [ "hypopharyngeal glands" ], "type": "factoid", "id": "6056fef294d57fd87900001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The hypopharyngeal glands (HGs) of honey bee nurse workers secrete the major protein fraction of jelly, a protein and lipid rich substance fed to developing larvae, other worker bees, and queens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30953617", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 354, "text": "The first MRJP was identified in royal jelly, a secretion of the bees' hypopharyngeal glands that is used by young worker bees, called nurses, to feed developing larvae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31410279", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "The nurse hypopharyngeal glands produce the protein fraction of the worker and royal jelly that is fed to developing larvae and queens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30272666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 330, "text": "The hypopharyngeal glands (HPGs) of worker honeybees undergo physiological changes along with the age-dependent role change from nursing to foraging: nurse bee HPGs secrete mainly major royal jelly proteins, whereas forager HPGs secrete mainly \u03b1-glucosidase III, which converts the sucrose in the nectar into glucose and fructose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26083737", "endSection": "abstract" } ] }, { "body": "List the common retinal diseases associated with circRNAs.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34858342", "http://www.ncbi.nlm.nih.gov/pubmed/32519377", "http://www.ncbi.nlm.nih.gov/pubmed/30259375", "http://www.ncbi.nlm.nih.gov/pubmed/30917906", "http://www.ncbi.nlm.nih.gov/pubmed/29288268", "http://www.ncbi.nlm.nih.gov/pubmed/34738746", "http://www.ncbi.nlm.nih.gov/pubmed/32343678", "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "http://www.ncbi.nlm.nih.gov/pubmed/32500032", "http://www.ncbi.nlm.nih.gov/pubmed/32914551", "http://www.ncbi.nlm.nih.gov/pubmed/34422901", "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "http://www.ncbi.nlm.nih.gov/pubmed/34173806", "http://www.ncbi.nlm.nih.gov/pubmed/31452702", "http://www.ncbi.nlm.nih.gov/pubmed/31636010", "http://www.ncbi.nlm.nih.gov/pubmed/31692917" ], "ideal_answer": [ "Circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for retinal degeneration, diabetic retinopathy, proliferative diabetic retinopathy (PDR) and Retinopathy of prematurity (ROP)" ], "exact_answer": [ [ "Diabetic retinopathy" ], [ "proliferative diabetic retinopathy" ], [ "retinal neovascular diseases" ], [ "retinal degeneraion" ] ], "type": "list", "id": "622122683a8413c653000075", "snippets": [ { "offsetInBeginSection": 1618, "offsetInEndSection": 1772, "text": "The present findings indicate that hsa_circ_0001953 in the whole blood may serve as a novel diagnostic biomarker and potential therapeutic target for PDR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32914551", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 180, "text": "This study aimed to determine whether circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for proliferative diabetic retinopathy (PDR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32914551", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 208, "text": "iabetic retinopathy is a frequent complication of diabetes mellitus and one of the common causes of blindness. Circular RNAs (circRNAs) can modulate various biological behaviors of human diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34173806", "endSection": "abstract" }, { "offsetInBeginSection": 1535, "offsetInEndSection": 1812, "text": "Our findings unraveled that circ_0084043 promoted the HG-induced retinal pigment epithelial cell injury through activating the Wnt/\u03b2-catenin signal pathway by the miR-128-3p/TXNIP axis. Circ_0084043 might be an available biomarker in diabetic retinopathy diagnosis and therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34173806", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1569, "text": ". The results of the present study suggest that the identified set of circRNA transcripts and the potential regulatory mechanisms for the development of ROP are worthy of functional studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31452702", "endSection": "abstract" }, { "offsetInBeginSection": 1385, "offsetInEndSection": 1532, "text": "The results together suggested that circRNAs were aberrantly expressed in OIR retinas and may play potential roles in retinal neovascular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692917", "endSection": "abstract" }, { "offsetInBeginSection": 1195, "offsetInEndSection": 1367, "text": "Therefore, circRims2 may play an important role in the maintenance of retinal structure and function, and circRims2 deficiency may lead to pathogenic changes in the retina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34738746", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 299, "text": "ases. Circ_0084043 is a novel circRNA, and its function in diabetic retinopathy progression is un", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34173806", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 1018, "text": " we consider the current state of knowledge regarding the potential role and underlying mechanism of circRNAs in ocular diseases including pterygium, age-related cataract, glaucoma, diabetic retinopathy, retinoblastoma, retinal vascular dysfunction and hyperhomocysteinemia induced ocular diseases, emphasizing that circRNAs could be promising biomarkers for the diagnosis and prognosis evaluation. Future circRNAs-ta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "endSection": "abstract" }, { "offsetInBeginSection": 388, "offsetInEndSection": 651, "text": "3, an example of circRNA, is frequently expressed in many diseases, such as diabetes, age-related cataract, idiopathic pulmonary fibrosis, preeclampsia, osteoblasts, and retinal vascular dysfunction, leading to disease development and progression. In addition, ci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32500032", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "This study investigated the profile of circular RNA (circRNA) expression and its epigenetic role associated with human retinoblastoma (RB). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30917906", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 437, "text": " present study, we identified altered circRNAs in the retinas of oxygen-induced retinopathy (OIR) mouse model by microarray profiling. Microar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692917", "endSection": "abstract" }, { "offsetInBeginSection": 103, "offsetInEndSection": 344, "text": "iseases. Previous study has revealed that circ_0005941 (also known as circFTO, an alpha-ketoglutarate-dependent dioxygenase) was upregulated in the vitreous humor of diabetic retinopathy (DR), while its underlying mechanism in DR remains unk", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34422901", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Oxygen-induced circRNA profiles and coregulatory networks in a retinopathy of prematurity mouse model", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31452702", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Identifying circRNA-associated-ceRNA networks in retinal neovascularization in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692917", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Retinal neovascularization is a complication which caused human vision loss severely.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692917", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 288, "text": "However, circRNA expression profile and the underlying mechanisms in retinal neovascular diseases remain unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692917", "endSection": "abstract" }, { "offsetInBeginSection": 289, "offsetInEndSection": 429, "text": "In the present study, we identified altered circRNAs in the retinas of oxygen-induced retinopathy (OIR) mouse model by microarray profiling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31692917", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 955, "text": "Here we will summarize the functions of circRNAs in vascular diseases, including vascular dysfunction, atherosclerosis, diabetes mellitus-related retinal vascular dysfunction, chronic thromboembolic pulmonary hypertension, carotid atherosclerotic disease, hepatic vascular invasion in hepatocellular carcinoma, aortic aneurysm, coronary artery disease, and type 2 diabetes mellitus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259375", "endSection": "abstract" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1248, "text": "This review summarizes our current perception of the properties, biogenesis, and functions of circRNAs and the development of circRNA researches related to ophthalmologic diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, corneal neovascularization, cataract, pterygium, proliferative vitreoretinopathy, retinoblastoma, and ocular melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 999, "text": "In this review we consider the current state of knowledge regarding the potential role and underlying mechanism of circRNAs in ocular diseases including pterygium, age-related cataract, glaucoma, diabetic retinopathy, retinoblastoma, retinal vascular dysfunction and hyperhomocysteinemia induced ocular diseases, emphasizing that circRNAs could be promising biomarkers for the diagnosis and prognosis evaluation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Circular RNA-ZNF532 regulates diabetes-induced retinal pericyte degeneration and vascular dysfunction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32343678", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Purpose: To reveal the expression profile and clinical significance of circular RNAs (circRNAs) in diabetic retinopathy (DR).Methods: Circular RNA microarrays were performed to identify DR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29288268", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 735, "text": "Recent studies recognized the vital roles that circRNAs played in the pathogenesis of various eye diseases, highlighting circRNAs as promising biomarkers for diagnosis and assessment of progression and prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Emerging roles of non-coding RNAs in retinal diseases: A review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32519377", "endSection": "title" }, { "offsetInBeginSection": 720, "offsetInEndSection": 828, "text": "We also review how does these ncRNAs function in various retinal diseases including animal and human models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32519377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Downregulation of circRNA DMNT3B contributes to diabetic retinal vascular dysfunction through targeting miR-20b-5p and BAMBI.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31636010", "endSection": "title" }, { "offsetInBeginSection": 105, "offsetInEndSection": 316, "text": "Despite\u00a0emerging evidence indicating that circRNAs are abundantly expressed in various tissues, especially in the brain and retina, the role of circRNAs in retinal function and diseases is still largely unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34738746", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 536, "text": "As), lncRNAs (lncRNAs), and circRNAs (circRNAs) have been shown to be widely involved in the regulation of gene expression and affect multiple biological processes of retinopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34858342", "endSection": "abstract" } ] }, { "body": "How do CYP1A2 polymorphisms affect the habitual coffee consumption effect on apetite?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34564706" ], "ideal_answer": [ "The CYP1A2 polymorphism -163C\u2009>\u2009A (rs762551) polymorphism renders carriers: rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers.\nHigh coffee consumption was more prevalent in rapid compared to slow metabolizers (P\u2009=\u20090.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption\u2009=\u20090.002 and 0.048, respectively)." ], "type": "summary", "id": "620bedb13a8413c653000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34564706", "endSection": "title" }, { "offsetInBeginSection": 1965, "offsetInEndSection": 2166, "text": "CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34564706", "endSection": "abstract" }, { "offsetInBeginSection": 1101, "offsetInEndSection": 1657, "text": "Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P\u2009=\u20090.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption\u2009=\u20090.002 and 0.048, respectively). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34564706", "endSection": "abstract" }, { "offsetInBeginSection": 877, "offsetInEndSection": 1091, "text": "Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C\u2009>\u2009A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34564706", "endSection": "abstract" } ] }, { "body": "What is the role of SDE2?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33127907", "http://www.ncbi.nlm.nih.gov/pubmed/34365507" ], "ideal_answer": [ "SDE2 is a previously uncharacterized essential gene required for ribosome biogenesis and the regulation of alternative splicing.", "The role of SDE2 is to regulate RNA splicing and ribosome biogenesis.", "SDE2 is required for ribosome biogenesis and the regulation of alternative splicing", "Silencing Defective 2 (SDE2) is an essential gene required for ribosome biogenesis and the regulation of alternative splicing. SDE2 depletion leads to widespread changes in alternative splicing, defects in ribosome biogenesis and ultimately complete loss of cell viability.", "SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing." ], "type": "summary", "id": "620be7613a8413c653000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34365507", "endSection": "title" }, { "offsetInBeginSection": 553, "offsetInEndSection": 1093, "text": " Here, we demonstrate that Silencing Defective 2 (SDE2) is both an RNA binding protein and also a trans-acting adaptor protein that functions to regulate RNA splicing and ribosome biogenesis. SDE2 depletion leads to widespread changes in alternative splicing, defects in ribosome biogenesis and ultimately complete loss of cell viability. Our data highlight SDE2 as a previously uncharacterized essential gene required for the assembly and maturation of the complexes that carry out two of the most fundamental processes in mammalian cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34365507", "endSection": "abstract" }, { "offsetInBeginSection": 108, "offsetInEndSection": 310, "text": "Here, we report that SDE2, a PCNA-associated protein, plays a key role in maintaining active replication and counteracting replication stress by regulating the replication fork protection complex (FPC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33127907", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 500, "text": "SDE2 directly interacts with the FPC component TIMELESS (TIM) and enhances its stability, thereby aiding TIM localization to replication forks and the coordination of replisome progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33127907", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the CABENUVA pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33176247", "http://www.ncbi.nlm.nih.gov/pubmed/32495274", "http://www.ncbi.nlm.nih.gov/pubmed/32461114", "http://www.ncbi.nlm.nih.gov/pubmed/34408543", "http://www.ncbi.nlm.nih.gov/pubmed/33872258" ], "ideal_answer": [ "Cabenuva contains cabotegravir and rilpivirine. It is used for treatment of HIV." ], "exact_answer": [ [ "cabotegravir" ], [ "rilpivirine" ] ], "type": "list", "id": "602738ac1cb411341a0000d7", "snippets": [ { "offsetInBeginSection": 762, "offsetInEndSection": 939, "text": "Cabenuva\u2122 is recently approved by Health Canada containing LA cabotegravir+LA rilpivirine nanocrystals (ViiV healthcare) for once monthly administration by intramuscular route. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32461114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "A regimen comprising extended release injectable suspensions of cabotegravir and rilpivirine for concurrent administration (CABENUVA\u2122) is being developed by ViiV Healthcare and Janssen Pharmaceutica (Janssen) as a complete regimen for HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32495274", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 599, "text": "The clinical phase III trials of FLAIR and ATLAS, showed two-drug injectable cabotegravir (CAB) and rilpivirine (RPV) formulation is potent, safe, and tolerable in HIV-infected patients. The recent approval of cabenuva (CAB+RPV) by Health Canada is a milestone in the development of long-term therapies for HIV infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33176247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 253, "text": "A regimen comprising extended release injectable suspensions of cabotegravir and rilpivirine for concurrent administration (CABENUVA\u2122) is being developed by ViiV Healthcare and Janssen Pharmaceutica (Janssen) as a complete regimen for HIV infection. Bas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32495274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "The approval of the novel long-acting HIV injection; Cabenuva\u00ae- Cabotegravir and Rilpivirine injectable formulation) and the recent call by the World Health Organization for promoting community-based ART management, underscore the remarkable progress towards meeting the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets by 2030. As t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34408543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Cabenuva-an injectable formulation of cabotegravir and rilpivirine and the first injectable complete therapy for adults with HIV-1-is now approved.It is administered once a month as two intramuscular injections following a month of treatment with the oral forms of these drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33872258", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 938, "text": "Cabenuva\u2122 is recently approved by Health Canada containing LA cabotegravir+LA rilpivirine nanocrystals (ViiV healthcare) for once monthly administration by intramuscular route.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32461114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "The approval of the novel long-acting HIV injection; Cabenuva\u00ae- Cabotegravir and Rilpivirine injectable formulation) and the recent call by the World Health Organization for promoting community-based ART management, underscore the remarkable progress towards meeting the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets by 2030.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34408543", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 598, "text": "The recent approval of cabenuva (CAB+RPV) by Health Canada is a milestone in the development of long-term therapies for HIV infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33176247", "endSection": "abstract" } ] }, { "body": "What is Shone's complex?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27456367", "http://www.ncbi.nlm.nih.gov/pubmed/33032391", "http://www.ncbi.nlm.nih.gov/pubmed/33070402", "http://www.ncbi.nlm.nih.gov/pubmed/31483300" ], "ideal_answer": [ "Shone's syndrome is a rare congenital heart disease that includes 4 cardiovascular anomalies: supravalvular mitral ring, parachute mitral valve, subaortic stenosis, and coarctation of the aorta." ], "type": "summary", "id": "60805f0c4e6a4cf630000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Shone's syndrome is a rare congenital heart disease that includes 4 cardiovascular anomalies: supravalvular mitral ring, parachute mitral valve, subaortic stenosis, and coarctation of the aorta. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33070402", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 119, "text": " Shone's complex is a rare lesion affecting the mitral valve (MV) and left ventricular outflow tract (LVOT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33032391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Shone's complex is a rare congenital cardiac malformation characterized by serial obstructive lesions of the left heart at multiple levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31483300", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 127, "text": "Shone's syndrome is a complex consisting of mitral valve stenosis in addition to left ventricle outflow obstruction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27456367", "endSection": "abstract" } ] }, { "body": "What methods are used to diagnose bowel endometriosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32344709", "http://www.ncbi.nlm.nih.gov/pubmed/30689680", "http://www.ncbi.nlm.nih.gov/pubmed/21822742", "http://www.ncbi.nlm.nih.gov/pubmed/34241976", "http://www.ncbi.nlm.nih.gov/pubmed/8566249", "http://www.ncbi.nlm.nih.gov/pubmed/17209363", "http://www.ncbi.nlm.nih.gov/pubmed/17151903", "http://www.ncbi.nlm.nih.gov/pubmed/18439504", "http://www.ncbi.nlm.nih.gov/pubmed/20954166", "http://www.ncbi.nlm.nih.gov/pubmed/17572918", "http://www.ncbi.nlm.nih.gov/pubmed/32620408", "http://www.ncbi.nlm.nih.gov/pubmed/25782295", "http://www.ncbi.nlm.nih.gov/pubmed/28882922", "http://www.ncbi.nlm.nih.gov/pubmed/21493029", "http://www.ncbi.nlm.nih.gov/pubmed/18382872", "http://www.ncbi.nlm.nih.gov/pubmed/30964888", "http://www.ncbi.nlm.nih.gov/pubmed/25757812", "http://www.ncbi.nlm.nih.gov/pubmed/33417291", "http://www.ncbi.nlm.nih.gov/pubmed/31587576", "http://www.ncbi.nlm.nih.gov/pubmed/34182605", "http://www.ncbi.nlm.nih.gov/pubmed/32698994" ], "ideal_answer": [ "Double-contrast barium enema (DCBE), transrectal endoscopic ultrasonography (REU), multidetector computerized tomography enema (MDCT-e), and computed tomography colonoscopy (CTC) have been successfully used for the diagnosis of bowel endometriosis." ], "exact_answer": [ [ "Trans vaginal ultrasound" ], [ "Double-contrast barium enema" ], [ "endoscopic ultrasonography" ], [ "multidetector CT enema" ], [ "computed tomography colonoscopy" ], [ "MRI" ], [ "CT" ], [ "rectal endoscopic sonography (RES)" ], [ "Speckle sign" ] ], "type": "list", "id": "621eb1d83a8413c653000059", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "Double-contrast barium enema (DCBE), transrectal endoscopic ultrasonography (REU), multidetector computerized tomography enema (MDCT-e), and computed tomography colonoscopy (CTC) have been successfully used for the diagnosis of bowel endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32698994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Transvaginal ultrasonography (TVS) should be the first-line investigation in patients with suspicion of deep endometriosis and, in particular, of rectosigmoid endometriosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620408", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 115, "text": " To determine usefulness of the \"speckle sign\" in the diagnosis of deep invasive endometriosis.MATERIALS ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33417291", "endSection": "abstract" }, { "offsetInBeginSection": 1454, "offsetInEndSection": 1641, "text": " The speckle sign could be helpful in making the diagnosis of posterior compartment endometriosis, and the sign is often found in conjunction with other imaging features of endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33417291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Transvaginal sonography determines accurately extent of infiltration of rectosigmoid deep endometriosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34182605", "endSection": "title" }, { "offsetInBeginSection": 2263, "offsetInEndSection": 2439, "text": "Preoperative TVS determines accurately rectosigmoid DE lesion length. TVS can thereby contribute to optimal planning of surgical treatment options in women with rectosigmoid DE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34182605", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 184, "text": "Surgical excision of deep infiltrating endometriosis (DIE) is complex and associated with morbidity. Diagnostic imaging plays an important role in the preoperative workup", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34241976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Deep infiltrating endometriosis of the bowel: MR imaging as a method to predict muscular invasion.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21822742", "endSection": "title" }, { "offsetInBeginSection": 163, "offsetInEndSection": 438, "text": "iltration. Transvaginal sonography (TVS) and magnetic resonance imaging (MRI) have been used for noninvasive diagnosis and preoperative mapping of rectosigmoid endometriosis (RE), but no consensus has been reached so far regarding which method is the most accurate in this se", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30964888", "endSection": "abstract" }, { "offsetInBeginSection": 378, "offsetInEndSection": 555, "text": "ological techniques (such as magnetic resonance imaging and multidetector computerized tomography enteroclysis) are useful for estimating the extent of bowel endometriosis. Horm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30689680", "endSection": "abstract" }, { "offsetInBeginSection": 365, "offsetInEndSection": 560, "text": "). Transrectal ultrasound scanning can be applied as a preoperative tool to predict the presence of rectovaginal endometriosis and bowel wall involvement (Abrao et al., J Am Assoc Gynecol Laparos", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18382872", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 336, "text": "features. The aim of this study is to assess the value of MR diffusion-weighted imaging (DWI) in differentiating endometriosis infiltrating the bowel from colorectal c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21493029", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 460, "text": "objective of the current study was to compare the performance of three-dimensional rectal water contrast transvaginal ultrasonography (3D-RWC-TVS) and computed tomographic colonography (CTC) in predicting the presence and characteristics of rectosigmoid endometriosis. (2) Me", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32344709", "endSection": "abstract" }, { "offsetInBeginSection": 1543, "offsetInEndSection": 1678, "text": "e first study comparing the performance of 3D-RWC-TVS and CTC in the diagnosis of rectosigmoid endometriosis. Both techniques allowed f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32344709", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Accuracy of transvaginal sonography versus magnetic resonance imaging in the diagnosis of rectosigmoid endometriosis: Systematic review and meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30964888", "endSection": "title" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1124, "text": "t difference in the accuracy of 3D-RWC-TVS and CTC in diagnosing the presence of rectosigmoid endometriotic nodules (p = 0.118), although CTC was more precise in diagnosing endometriosis located in the sigmoid (p = 0.016). 3D-RWC-TVS and CTC ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32344709", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1008, "text": "opy seems to be the best diagnostic method of intestinal endometriosis and its treatment is to remove the involved part of the bowel together with endometriotic foci and surrounding tissues. Cyclic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "PURPOSE: To evaluate magnetic resonance (MR) imaging morphologic- and signal intensity abnormalities of deep infiltrating endometriosis (DIE) of the bowel wall and to assess its value in predicting depth and extent of bowel wall infiltra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21822742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8566249", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "OBJECTIVES: To evaluate a clinical examination during menstruation and plasma CA-125 concentrations to diagnose deep endometriosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8566249", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 356, "text": "SIGN: Prospective study in 61 women scheduled for a laparoscopy, a retrospective study in 140 women with deep endometriosis, and a clinical validation study in 16 women with painful pelvic nodularities during menstruation.S", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8566249", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 552, "text": "S: In the retrospective study, deep endometriosis was detected by routine clinical examination in only 36% of women. Lesi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8566249", "endSection": "abstract" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1047, "text": "5 concentrations were higher during menstruation and correlated with deep endometriosis and with deep and cystic ovarian endometriosis. Nodu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8566249", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 786, "text": "ld be used. Several techniques have been proposed for the diagnosis of bowel endometriosis including double-contrast barium enema, transvaginal ultrasonography, rectal endoscopic ultrasonography, magnetic resonance imaging, and multislice computed tomography e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17572918", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 303, "text": "We used multislice computerized tomography (CT) combined with the distention of the colon by rectal enteroclysis (MSCTe) for the diagnosis of bowel endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17151903", "endSection": "abstract" }, { "offsetInBeginSection": 803, "offsetInEndSection": 1001, "text": "Laparoscopy seems to be the best diagnostic method of intestinal endometriosis and its treatment is to remove the involved part of the bowel together with endometriotic foci and surrounding tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17209363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Double-contrast barium enema and transrectal endoscopic ultrasonography in the diagnosis of intestinal deeply infiltrating endometriosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18439504", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Rectal water contrast transvaginal ultrasound versus double-contrast barium enema in the diagnosis of bowel endometriosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28882922", "endSection": "title" }, { "offsetInBeginSection": 771, "offsetInEndSection": 1040, "text": "y laparoscopy as well as histopathology. For bowel endometriosis diagnosis, DCBE and RWC-TVS demonstrated sensitivities of 96.4% and 88.2%, specificities of 100% and 97.3%, positive prediction values of 100% and 98.0%, negative prediction values of 98.0% and 88.0%, acc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28882922", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 339, "text": "OBJECTIVE: To critically analyze the diagnostic value of transvaginal sonography (TVS) for non-invasive, presurgical detection of bowel endometriosis.METHODS: MEDLINE (1966-2010) and EMBASE (1980-2010) databases were searched for relevant studies investigating the diagnostic accuracy of TVS for diagnosing deep infiltrating endometriosis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20954166", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 550, "text": "Radiological techniques (such as magnetic resonance imaging and multidetector computerized tomography enteroclysis) are useful for estimating the extent of bowel endometriosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30689680", "endSection": "abstract" }, { "offsetInBeginSection": 811, "offsetInEndSection": 1097, "text": "MDCT-e is accurate and reproducible in diagnosing intestinal endometriosis and in assessing its characteristics: the largest diameter of the nodule, the distance between the distal part of the nodule and the anal verge, and depth of infiltration of endometriosis in the intestinal wall.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32698994", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1320, "text": "The potential of MSCTe for the diagnosis of bowel endometriosis relies on the fact that the serosal, muscular, and mucosal layers of the bowel wall can be evaluated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17151903", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1244, "text": "he disease. Bowel endometriotic nodules can be removed by various techniques: mucosal skinning, nodulectomy, full thickness disc resection, and segmenta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17572918", "endSection": "abstract" }, { "offsetInBeginSection": 413, "offsetInEndSection": 651, "text": "Method: Between 2009 and 2017, we operated 121 patients with bowel endometriosis, and built up a prospective database where we assessed their wish of pregnancy, the way of the conception, pathologies during pregnancy and mode of delivery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31587576", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 373, "text": "Transvaginal ultrasonography is the first line investigation in patients with suspected bowel endometriosis and allows accurate determination of the presence of the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30689680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "UNLABELLED: Bowel endometriosis opens a new frontier for the gynecologist, as it forces the understanding of a new anatomy, a new physiology, and a ne", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17572918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Contribution of Computed Tomography Enema and Magnetic Resonance Imaging to Diagnose Multifocal and Multicentric Bowel Lesions in Patients With Colorectal Endometriosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25757812", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Diagnostic accuracy of transvaginal ultrasound for non-invasive diagnosis of bowel endometriosis: systematic review and meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20954166", "endSection": "title" }, { "offsetInBeginSection": 680, "offsetInEndSection": 897, "text": "Hence, when diagnosing deep infiltrating endometriosis, MRI should be complemented with transvaginal ultrasonography to detect endometrioid implants on the bowel walls as the informative value in this aspect is above.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25782295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 40, "text": "Ultrasonography for bowel endometriosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620408", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 597, "text": "STUDY OBJECTIVE: To evaluate the diagnostic contribution of the computed tomography (CT) enema and magnetic resonance imaging (MRI) for multifocal (multiple lesions affecting the same segment) and multicentric (multiple lesions affecting several digestive segments) bowel endometriosis.DESIGN: Prospective cohort study (Canadian Task Force classification II-2).PATIENTS: Eighty-five patients.SETTING: Tenon University Hospital, Paris, France.INTERVENTION: All patients received a preoperative CT enema and underwent MRI interpreted by 2 radiologists.MEASUREMENTS AND MAIN RESULTS: Patients underwe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25757812", "endSection": "abstract" } ] }, { "body": "When did FDA approve the first B-cell maturation antigen-targeted CAR-T cell therapy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34549909", "http://www.ncbi.nlm.nih.gov/pubmed/32683672" ], "ideal_answer": [ "FDA approved the first B-cell maturation antigen-targeted CAR-T cell therapy on March 26, 2021." ], "exact_answer": [ "26 March 2021" ], "type": "factoid", "id": "621145c63a8413c65300000c", "snippets": [ { "offsetInBeginSection": 288, "offsetInEndSection": 551, "text": "The most recent US Food and Drug Administration approval of the first B-cell maturation antigen-targeted CAR-T cell therapy on March 26, 2021, has paved a path forward for the eventual evaluation of more of these investigational agents undergoing clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34549909", "endSection": "abstract" } ] }, { "body": "Describe the N6-methyladenosine RNA modification in AML", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33337619" ], "ideal_answer": [ "The N6-methyladenosine RNA modification in AML is a nucleotide that is not normally found in the DNA of cancer cells. This nucleotide has been shown to have an effect on the cell's ability to divide.", "The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells. Similar observations were made with the demethylases fat mass and obesity-associated protein and AlkB homologue 5 RNA demethylase. Of importance, loss of any of these genes has little to no effect on normal hemopoietic stem cells, suggesting therapeutic potential.", "The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells.", "the N6-methyladenosine (m6A) modification of RNA has been shown to play an important role in the development of acute myeloid leukemia (AML) and the maintenance of leukemic stem cells (LSCs)", "The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells. Similar observations were made with the demethylases fat mass and obesity-associated protein and AlkB homologue 5 RNA demethylase." ], "type": "summary", "id": "62128c503a8413c653000018", "snippets": [ { "offsetInBeginSection": 498, "offsetInEndSection": 1005, "text": "The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells. Similar observations were made with the demethylases fat mass and obesity-associated protein and AlkB homologue 5 RNA demethylase. Of importance, loss of any of these genes has little to no effect on normal hemopoietic stem cells, suggesting therapeutic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33337619", "endSection": "abstract" } ] }, { "body": "Does trimetazidine protect from myocardial injury after percutaneous coronary intervention?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32877651" ], "ideal_answer": [ "Oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice." ], "exact_answer": "no", "type": "yesno", "id": "6027446d1cb411341a0000dd", "snippets": [ { "offsetInBeginSection": 2053, "offsetInEndSection": 2472, "text": "After a median follow-up of 47\u00b75 months (IQR 42\u00b73-53\u00b73), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23\u00b73%] patients) and the placebo group (714 [23\u00b77%]; hazard ratio 0\u00b798 [95% CI 0\u00b788-1\u00b709], p=0\u00b773). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32877651", "endSection": "abstract" }, { "offsetInBeginSection": 2823, "offsetInEndSection": 3175, "text": "INTERPRETATION: Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32877651", "endSection": "abstract" } ] }, { "body": "When is the drug Ivermectin used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31786697", "http://www.ncbi.nlm.nih.gov/pubmed/31758387", "http://www.ncbi.nlm.nih.gov/pubmed/31808594" ], "ideal_answer": [ "Ivermectin (IVM) has been well known for its role in the treatment of parasitic diseases, due to its effect on glutamate-gated chloride channels. These same channels are also present in the mosquito vector, and thus, research has focused on the insecticidal effects of this drug." ], "exact_answer": [ "Ivermectin is used to treat parasitic diseases" ], "type": "factoid", "id": "6049173d1cb411341a00016b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 403, "text": "The aim of this study was to compare the economic revenue related to the use of low- or high-efficacy anthelmintic drugs within suppressive or strategic schemes of treatment in growing heifers. Heifers raised in a semi-intensive grazing system in southern Brazil were used. Levamisole and ivermectin were selected as the high- and the low-efficacy drugs, respectively, based on a previous efficacy test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31758387", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 433, "text": "Ivermectin (IVM) has been well known for its role in the treatment of parasitic diseases, due to its effect on glutamate-gated chloride channels. These same channels are also present in the mosquito vector, and thus, research has focused on the insecticidal effects of this drug. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31786697", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 161, "text": "Ivermectin is safe and widely used for treating helminth infections. It also kills arthropods feeding on treated subjects, including malaria vectors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31808594", "endSection": "abstract" } ] }, { "body": "What is the function of a DEAD box protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18729217", "http://www.ncbi.nlm.nih.gov/pubmed/16505350", "http://www.ncbi.nlm.nih.gov/pubmed/15572142", "http://www.ncbi.nlm.nih.gov/pubmed/11598190", "http://www.ncbi.nlm.nih.gov/pubmed/33465637", "http://www.ncbi.nlm.nih.gov/pubmed/7731693", "http://www.ncbi.nlm.nih.gov/pubmed/22899052", "http://www.ncbi.nlm.nih.gov/pubmed/8144024", "http://www.ncbi.nlm.nih.gov/pubmed/22940866", "http://www.ncbi.nlm.nih.gov/pubmed/26127001", "http://www.ncbi.nlm.nih.gov/pubmed/33656655", "http://www.ncbi.nlm.nih.gov/pubmed/32669294", "http://www.ncbi.nlm.nih.gov/pubmed/23815438", "http://www.ncbi.nlm.nih.gov/pubmed/19748356", "http://www.ncbi.nlm.nih.gov/pubmed/33262215", "http://www.ncbi.nlm.nih.gov/pubmed/23606618", "http://www.ncbi.nlm.nih.gov/pubmed/23523990", "http://www.ncbi.nlm.nih.gov/pubmed/12086675", "http://www.ncbi.nlm.nih.gov/pubmed/23630256", "http://www.ncbi.nlm.nih.gov/pubmed/25095995", "http://www.ncbi.nlm.nih.gov/pubmed/19747077", "http://www.ncbi.nlm.nih.gov/pubmed/20016128", "http://www.ncbi.nlm.nih.gov/pubmed/22995829", "http://www.ncbi.nlm.nih.gov/pubmed/28650145", "http://www.ncbi.nlm.nih.gov/pubmed/21297876", "http://www.ncbi.nlm.nih.gov/pubmed/12867080" ], "ideal_answer": [ "DEAD-box helicases are ubiquitous in RNA-mediated processes and function by coupling cycles of ATP binding and hydrolysis to changes in affinity for single-stranded RNA.", "DEAD-box helicase proteins perform ATP-dependent rearrangements of structured RNAs", "DEAD-box (DDX) proteins belong to the largest subfamily of RNA helicase SF2, which contributes to all biological processes of RNA metabolism", "DEAD-box proteins catalyze the ATP-dependent unwinding of RNA duplexes and accompany RNA molecules throughout their cellular life." ], "type": "summary", "id": "6221468d3a8413c653000076", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "DEAD-box helicase proteins perform ATP-dependent rearrangements of structured RNAs throughout RNA biology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33262215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "DEAD-box proteins are ubiquitous in RNA-mediated processes and function by coupling cycles of ATP binding and hydrolysis to changes in affinity for single-stranded RNA. Many DEAD-box proteins use this basic mechanism as the foundation for a version of RNA helicase activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "DEAD-box proteins as RNA helicases and chaperones.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297876", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "RNA helicases of the DEAD-box and related families have been found to be required for all processes involving RNA molecules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12867080", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "DDX3 belongs to the DEAD-box proteins, a large family of ATP-dependent RNA helicases that participate in all aspects of RNA metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23606618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "DEAD-box proteins catalyze the ATP-dependent unwinding of RNA duplexes and accompany RNA molecules throughout their cellular life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25095995", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "DEAD-box (DDX) proteins belong to the largest subfamily of RNA helicase SF2, which contributes to all biological processes of RNA metabolism", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33465637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "DDX3Y (also known as DBY) is a member of the DEAD box protein family, which is involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20016128", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "VASA is a member of the DEAD-box protein family that plays an indispensable role in mammalian spermatogenesis, particularly during meiosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26127001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: Vasa is a member of the DEAD-box protein family that plays an indispensable role in mammalian spermatogenesis, particularly during meiosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23815438", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The yeast DEAD box protein Mss116p is a general RNA chaperone that functions in mitochondrial group I and II intron splicing, translational activation, and RNA end processing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19748356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "DEAD box proteins are putative RNA helicases that function in all aspects of RNA metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing. B", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11598190", "endSection": "abstract" }, { "offsetInBeginSection": 259, "offsetInEndSection": 445, "text": "rom unwinding RNA duplexes, which established these proteins as RNA helicases, DEAD box proteins have been shown to also catalyse RNA annealing and to displace proteins from RNA. DEAD bo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23523990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "DDX3Y (also known as DBY) is a member of the DEAD box protein family, which is involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation. In ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20016128", "endSection": "abstract" }, { "offsetInBeginSection": 146, "offsetInEndSection": 342, "text": " 'DEAD/H' family of putative RNA helicases may help regulate these processes by utilizing intrinsic RNA-dependent ATPase activity to catalyze conformational changes in RNA secondary structure. To ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8144024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "DEAD-box helicases catalyze the ATP-dependent unwinding of RNA duplexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22995829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "A DEAD-box protein functions as an ATP-dependent RNA chaperone in group I intron splicing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086675", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "DEAD-box proteins are nonprocessive RNA helicases that play diverse roles in cellular processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28650145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "A DEAD-box protein alone promotes group II intron splicing and reverse splicing by acting as an RNA chaperone.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16505350", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "DEAD/H-box proteins are involved in various aspects of RNA metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18729217", "endSection": "abstract" }, { "offsetInBeginSection": 551, "offsetInEndSection": 703, "text": "Our results demonstrate that a DExH/D-box protein has a specific, physiologically relevant chaperone function in the folding of a natural RNA substrate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12086675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "DEAD-box proteins are the largest family of nucleic acid helicases, and are crucial to RNA metabolism throughout all domains of life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22940866", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 828, "text": "Here, structural, biochemical and genetic analyses of the yeast DEAD-box protein Mss116p indicate that the helicase core domains have modular functions that enable a novel mechanism for RNA-duplex recognition and unwinding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22940866", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The DEAD-box RNA helicase family comprise enzymes that participate in every aspect of RNA metabolism, associated with a diverse range of cellular functions including response to abiotic stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22899052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The Thermus thermophilus DEAD-box protein Hera is a general RNA binding protein and plays a key role in tRNA metabolism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32669294", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "DEAD-box proteins, a large class of RNA-dependent ATPases, regulate all aspects of gene expression and RNA metabolism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23630256", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "DEAD box proteins are putative RNA helicases that have been implicated in cellular processes involving alteration of RNA secondary structure, such as translation initiation and splicing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7731693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "DEAD box proteins catalyze the ATP-dependent unwinding of double-stranded RNA (dsRNA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19747077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "DEAD-box proteins are ATP-dependent RNA helicases that function in various stages of RNA processing and in RNP remodeling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15572142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "DEAD-box proteins are ubiquitous in RNA-mediated processes and function by coupling cycles of ATP binding and hydrolysis to changes in affinity for single-stranded RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297876", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 624, "text": "DEAD-box proteins ordinarily function as constituents of enormous multi-protein complexes and it is believed that interactions with other components in the complexes might be answerable for the various capacities ascribed to these proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33656655", "endSection": "abstract" }, { "offsetInBeginSection": 911, "offsetInEndSection": 1130, "text": "There is emerging evidence that DEAD-box family of RNA helicases play pivotal functions in various cellular processes and in numerous cases have been embroiled in cellular proliferation and/or neoplastic transformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33656655", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 613, "text": "This activity, coupled with mechanisms to direct different DEAD-box proteins to their physiological substrates, allows them to promote RNA folding steps and rearrangements and to accelerate remodeling of RNA\u2013protein complexes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297876", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 386, "text": "Many DEAD-box proteins use this basic mechanism as the foundation for a version of RNA helicase activity, efficiently separating the strands of short RNA duplexes in a process that involves little or no translocation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297876", "endSection": "abstract" } ] }, { "body": "What is the effect of rHDL-apoE3 on vascular permeability?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34875308" ], "ideal_answer": [ "rHDL-apoE3 markedly improves vascular permeability as demonstrated by the reduced concentration of Evans Blue dye in tissues such as the stomach, the tongue and the urinary bladder and ameliorated hypercholesterolemia." ], "exact_answer": [ "Improves" ], "type": "factoid", "id": "6206b740c9dfcb9c0900003b", "snippets": [ { "offsetInBeginSection": 2985, "offsetInEndSection": 3531, "text": "Finally, administration of a single dose of rHDL-apoE3 in apoE KO mice markedly improved vascular permeability as demonstrated by the reduced concentration of Evans Blue dye in tissues such as the stomach, the tongue and the urinary bladder and ameliorated hypercholesterolemia.CONCLUSIONS: rHDL-apoE3 significantly enhanced EC migration in vitro, predominantly via overexpression of ID1 and subsequent activation of MEK1/2 and PI3K, and their downstream targets ERK1/2, AKT and p38 MAPK, respectively and improved vascular permeability in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34875308", "endSection": "abstract" } ] }, { "body": "What is inhibited by TH1579?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27827301" ], "ideal_answer": [ "TH1579 is a best-in-class MTH1 inhibitor.", "MTH1", "TH1579 inhibits the MTH1 protein, which is the protein that cancer cells rely on to make their DNA." ], "exact_answer": [ "MTH1" ], "type": "factoid", "id": "6217bf6a3a8413c65300001d", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 395, "text": "Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27827301", "endSection": "abstract" }, { "offsetInBeginSection": 1371, "offsetInEndSection": 1640, "text": "We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27827301", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Gemogenovatucel-T?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33271095" ], "ideal_answer": [ "Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-\u03b21 and TGF-\u03b22." ], "type": "summary", "id": "60281e461cb411341a0000f4", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 191, "text": "Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-\u03b21 and TGF-\u03b22. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "BACKGROUND: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-\u03b21 and TGF-\u03b22.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-\u03b21", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271095", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "BACKGROUND: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-\u03b21 and TGF-\u03b22", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271095", "endSection": "abstract" } ] }, { "body": "What is the Versene Solution used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28041835", "http://www.ncbi.nlm.nih.gov/pubmed/29244941", "http://www.ncbi.nlm.nih.gov/pubmed/8266579" ], "ideal_answer": [ "the Versene Solution is used for the detachment of stem cell sheets." ], "exact_answer": [ "for the detachment of cells" ], "type": "factoid", "id": "606b32af94d57fd879000060", "snippets": [ { "offsetInBeginSection": 1206, "offsetInEndSection": 1324, "text": " in 0.01 versene solution, containing 0.011% w/v trypsin (Difco), 0.4 mg/ml D-glucose, 0.17 mg/ml KCl, 1.7 mg/ml NaCl.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8266579", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 68, "text": " stem cell sheets detached by Versene solution ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28041835", "endSection": "title" }, { "offsetInBeginSection": 357, "offsetInEndSection": 492, "text": "The object of study was follicular thyroid carcinoma cells suspension prepared with use of Versene solution and 0.25% trypsin solution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29244941", "endSection": "abstract" } ] }, { "body": "Are circRNAs susceptible to degradation by RNase R?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30259366", "http://www.ncbi.nlm.nih.gov/pubmed/31556152", "http://www.ncbi.nlm.nih.gov/pubmed/32480219", "http://www.ncbi.nlm.nih.gov/pubmed/29170496", "http://www.ncbi.nlm.nih.gov/pubmed/26660425", "http://www.ncbi.nlm.nih.gov/pubmed/24865493", "http://www.ncbi.nlm.nih.gov/pubmed/33141028", "http://www.ncbi.nlm.nih.gov/pubmed/31160488", "http://www.ncbi.nlm.nih.gov/pubmed/34238421", "http://www.ncbi.nlm.nih.gov/pubmed/31269210", "http://www.ncbi.nlm.nih.gov/pubmed/31217510", "http://www.ncbi.nlm.nih.gov/pubmed/29167634", "http://www.ncbi.nlm.nih.gov/pubmed/33650643", "http://www.ncbi.nlm.nih.gov/pubmed/34453665", "http://www.ncbi.nlm.nih.gov/pubmed/34269929", "http://www.ncbi.nlm.nih.gov/pubmed/34232572", "http://www.ncbi.nlm.nih.gov/pubmed/27929395" ], "ideal_answer": [ "Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation.", "Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs.", "Yes. Circular RNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation." ], "exact_answer": "no", "type": "yesno", "id": "62211d6f3a8413c65300006f", "snippets": [ { "offsetInBeginSection": 204, "offsetInEndSection": 383, "text": "Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33141028", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Circular RNA (circRNA) has a closed-loop structure, and its 3' and 5' ends are directly covalently connected by reverse splicing, which is more stable than linear RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34269929", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 373, "text": "CircRNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31556152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 355, "text": "Circular RNAs (circRNAs) are a class of newly-identified non-coding RNA that lack 5' (cap) and 3' (polyadenylation) ends and are linked by a covalent bond to form a closed loop structure. In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32480219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 344, "text": "Circular RNAs (circRNAs) own unique capabilities to communicate with nucleic acids and ribonucleoproteins and are emerging as indispensable compositions of the regulatory messages encoded in the genome. Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167634", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 570, "text": "RNase R is a strong 3' to 5' exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865493", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 323, "text": "Lariat RNAs and circRNAs are both RNase R resistant RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865493", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 356, "text": "In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32480219", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 343, "text": "Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167634", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 408, "text": "Because circRNAs are not easily degraded by exonuclease RNase R, they can exist more stably in body fluids than linear RNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259366", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 912, "text": "Therefore, it is essential to perform the RT-qPCR validation step only after linear RNAs have been degraded using an exonuclease such as ribonuclease R (RNase R).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34232572", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 582, "text": "is a strong 3' to 5' exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance. Thus, RNase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24865493", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 507, "text": "sion of circRNAs is prevalent in tissues and body fluids,and their abnormal expression is related to tumor progression.circRNAs are stable even under the treatment of RNase R because of their circular conformation.As circRNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34238421", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 346, "text": "e to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs. Mo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167634", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 414, "text": "e circRNAs are not easily degraded by exonuclease RNase R, they can exist more stably in body fluids than linear RNAs. Based", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30259366", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 216, "text": " is stable, difficult to cleave and resistant to RNA exonuclease or RNase R degradation. circRN", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33650643", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 506, "text": "the unique structures, circRNAs are resistant to exonuclease RNase R and maintain stability more easily than linear RNAs. Rece", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31160488", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 365, "text": "rison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals. Conseque", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32480219", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 724, "text": " RT-PCR analysis showed that sheep circRNAs are resistant to RNase R digestion and are expressed in prenatal and postnatal pituitary glands. GO and ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29170496", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 1812, "text": "Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, and often exhibit cell-specific, and tissue-specific/developmental-stage-specific expression and can be largely independent of the expression levels of the linear host gene-encoded linear RNAs; 2) the biogenesis of circRNAs via back-splicing is different from the canonical splicing of linear RNAs; 3) circRNA biogenesis is regulated by specific cis-acting elements and trans-acting factors; 4) circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RNA-binding protein (RBP), regulators of splicing and transcription, modifiers of parental gene expression, and regulators of protein translation or being translated into peptides in various diseases; 5) circRNAs have been identified for their enrichment and stability in exosomes and detected in body fluids such as human blood, saliva, and cerebrospinal fluids, suggesting that these exo-circRNAs have potential applications as disease biomarkers and novel therapeutic targets; 6) several circRNAs are regulated by oxidative stress and mediate reactive oxygen species (ROS) production as well as promote ROS-induced cellular death, cell apoptosis, and inflammation; 7) circRNAs have also emerged as important regulators in atherosclerotic cardiovascular disease, metabolic disease, and cancers; 8) the potential mechanisms of several circRNAs have been described in diseases, hinting at their potential applications as novel therapeutic targets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33141028", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 474, "text": "To prove their circularity as well as biochemically enrich these transcripts, it has become standard in the field to use the 3'-5' exonuclease RNase R. Here, we demonstrate that standard protocols involving RNase R can fail to digest >20% of all highly expressed linear RNAs, but these shortcomings can largely be overcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269210", "endSection": "abstract" }, { "offsetInBeginSection": 777, "offsetInEndSection": 1039, "text": "We propose that such an R-loop dependent ciRNA degradation likely represents a mechanism that on one hand limits ciRNA accumulation by recruiting RNase H1 and on the other hand resolves R-loops for transcriptional elongation at some GC-rich ciRNA-producing loci.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34453665", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 419, "text": "As circular RNAs (circRNAs) are resistant to degradation by exonucleases, their abundance relative to linear RNAs can be used as a surrogate marker for mRNA stability in the absence of transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26660425", "endSection": "abstract" }, { "offsetInBeginSection": 676, "offsetInEndSection": 878, "text": "The synthetic circular sponge was resistant to digestion with RNase R. Luciferase assays and functional experiments showed that the circular multi-miR sponge was more stable than its linear counterpart.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31217510", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 665, "text": "RNAs with highly structured 3' ends, including snRNAs and histone mRNAs, are naturally resistant to RNase R, but can be efficiently degraded once a poly(A) tail has been added to their ends.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Thousands of eukaryotic protein-coding genes generate circular RNAs that have covalently linked ends and are resistant to degradation by exonucleases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269210", "endSection": "abstract" } ] }, { "body": "Does atemoya juice inhibit tye CYP3A4 enzyme?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34881402" ], "ideal_answer": [ "No, atemoya juice does not inhibit CYP3A4." ], "exact_answer": "no", "type": "yesno", "id": "62057f1ec9dfcb9c0900002e", "snippets": [ { "offsetInBeginSection": 838, "offsetInEndSection": 962, "text": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881402", "endSection": "abstract" } ] }, { "body": "Which processes are affected by pathogenic SPTBN1 variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34211179" ], "ideal_answer": [ "SPTBN1 variants lead to effects that affect \u03b2II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics." ], "exact_answer": [ [ "\u03b2II-spectrin stability" ], [ "Disrupt binding to key molecular partners" ], [ "Disturb cytoskeleton organization and dynamics" ] ], "type": "list", "id": "61f7fca6882a024a10000039", "snippets": [ { "offsetInBeginSection": 484, "offsetInEndSection": 1161, "text": "Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect \u03b2II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of \u03b2II-spectrin in the central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34211179", "endSection": "abstract" } ] }, { "body": "Describe the role of bevacizumab in radiosurgery for arteriovenous malformation.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29198888", "http://www.ncbi.nlm.nih.gov/pubmed/23929592", "http://www.ncbi.nlm.nih.gov/pubmed/27334738", "http://www.ncbi.nlm.nih.gov/pubmed/22324417", "http://www.ncbi.nlm.nih.gov/pubmed/34177536", "http://www.ncbi.nlm.nih.gov/pubmed/32216590", "http://www.ncbi.nlm.nih.gov/pubmed/25360851" ], "ideal_answer": [ "Bevacizumab is used for the treatment of severe, refractory perilesional edema due to an arteriovenous malformation treated with stereotactic radiosurgery." ], "type": "summary", "id": "601c40bb1cb411341a00001a", "snippets": [ { "offsetInBeginSection": 136, "offsetInEndSection": 651, "text": "One of the most common late complications of SRS is perilesional edema which can be treated with steroids. In addition to steroids, some new medical therapies are being investigated and one of the promising one is Bevacizumab; a monoclonal antibody against vascular endothelial growth factor (VEGF). In the cases of steroid resistant perilesional edemas, however bevacizumab has a late term effect resolution of symptoms and radiological improvement can be seen as late as more than 1,5 years after its initiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32216590", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1398, "text": " In the cases of steroid resistant perilesional edemas, bevacizumab can be used for reducing symptoms and even radiological perilesional edema as well.Results: In our case, we have seen the effect of bevacizumab for symptomatic perilesional edema in a AVM patient after SRS treatment after radiological / neurological recovery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32216590", "endSection": "abstract" }, { "offsetInBeginSection": 1700, "offsetInEndSection": 1940, "text": "Our study showed that bevacizumab was a long-term and effective treatment option for the cases with peritumoral edema resistant to glucocorticoid treatment, where the patient had conditions such as severe headache and neurological deficits.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32216590", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1171, "text": "In addition, 6 patients underwent repeat radiosurgery in the ICH group, and 7 patients used bevacizumab in the RIC group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29198888", "endSection": "abstract" }, { "offsetInBeginSection": 1840, "offsetInEndSection": 2100, "text": "This is the first reported case demonstrating the use of a 4D CTA and an MRI to delineate the AVM nidus for Gamma Knife radiosurgery, with complete obliteration of the nidus over time and subsequent management of associated radiation necrosis with bevacizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27334738", "endSection": "abstract" }, { "offsetInBeginSection": 547, "offsetInEndSection": 661, "text": "Recent reports have shown successful treatment of RN with intravenous bevacizumab, a monoclonal antibody for VEGF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25360851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Bevacizumab used for the treatment of severe, refractory perilesional edema due to an arteriovenous malformation treated with stereotactic radiosurgery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22324417", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 588, "text": "The authors present a case of an arteriovenous malformation of the central sulcus treated with Gamma Knife surgery. The patient developed perilesional edema 9 months after treatment and experienced severe headache and hemiparesis. Her symptoms were refractory to corticosteroid therapy and pain management. She was subsequently treated with bevacizumab with striking improvement in her symptoms and results of neuroimaging studies. This is the first time that bevacizumab has been used to control severe refractory perilesional edema related to an intracranial arteriovenous malformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22324417", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 588, "text": "This is the first time that bevacizumab has been used to control severe refractory perilesional edema related to an intracranial arteriovenous malformation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22324417", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Late recovery of stereotactic\u00a0radiosurgery induced perilesional edema of an arteriovenous malformation after bevacizumab treatment.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32216590", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Resolution of Radiation-Induced Necrosis in Arteriovenous Malformation with Bevacizumab: A Case Report and Review of Current Literature.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34177536", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Late recovery of stereotactic\u00a0radiosurgery induced perilesional edema of an arteriovenous malformation after bevacizumab treatment", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32216590", "endSection": "title" }, { "offsetInBeginSection": 180, "offsetInEndSection": 340, "text": "Twenty-nine patients with brain tumors or vascular malformations developed clinical and/or imaging evidence of ARE after SRS and were treated using bevacizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23929592", "endSection": "abstract" } ] }, { "body": "Is Mycobacterium abscessus a human pathogen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32662049", "http://www.ncbi.nlm.nih.gov/pubmed/34460298", "http://www.ncbi.nlm.nih.gov/pubmed/34526902", "http://www.ncbi.nlm.nih.gov/pubmed/34516254" ], "ideal_answer": [ "Yes,\nMycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates." ], "exact_answer": "yes", "type": "yesno", "id": "6217db763a8413c653000028", "snippets": [ { "offsetInBeginSection": 210, "offsetInEndSection": 302, "text": "Mycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32662049", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Mycobacterium abscessus has emerged as a successful pathogen owing to its intrinsic drug resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34460298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34516254", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Mycobacterium abscessus has been recognised as a dreadful respiratory pathogen among the non-tuberculous mycobacteria (NTM) because of misdiagnosis, prolonged therapy with poor treatment outcomes and a high cost. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34526902", "endSection": "abstract" } ] }, { "body": "What is the indication for Favipiravir?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34339547", "http://www.ncbi.nlm.nih.gov/pubmed/22809499", "http://www.ncbi.nlm.nih.gov/pubmed/34497279", "http://www.ncbi.nlm.nih.gov/pubmed/34044777", "http://www.ncbi.nlm.nih.gov/pubmed/33191372", "http://www.ncbi.nlm.nih.gov/pubmed/24563658", "http://www.ncbi.nlm.nih.gov/pubmed/33364790", "http://www.ncbi.nlm.nih.gov/pubmed/32097670", "http://www.ncbi.nlm.nih.gov/pubmed/33042544", "http://www.ncbi.nlm.nih.gov/pubmed/34592006", "http://www.ncbi.nlm.nih.gov/pubmed/24084488", "http://www.ncbi.nlm.nih.gov/pubmed/34539392", "http://www.ncbi.nlm.nih.gov/pubmed/33647553", "http://www.ncbi.nlm.nih.gov/pubmed/34548811", "http://www.ncbi.nlm.nih.gov/pubmed/34535038", "http://www.ncbi.nlm.nih.gov/pubmed/22429564", "http://www.ncbi.nlm.nih.gov/pubmed/32405421", "http://www.ncbi.nlm.nih.gov/pubmed/33746092", "http://www.ncbi.nlm.nih.gov/pubmed/28769016", "http://www.ncbi.nlm.nih.gov/pubmed/34464921", "http://www.ncbi.nlm.nih.gov/pubmed/28462833", "http://www.ncbi.nlm.nih.gov/pubmed/33624584", "http://www.ncbi.nlm.nih.gov/pubmed/22022624", "http://www.ncbi.nlm.nih.gov/pubmed/29765101", "http://www.ncbi.nlm.nih.gov/pubmed/34571361", "http://www.ncbi.nlm.nih.gov/pubmed/32645335", "http://www.ncbi.nlm.nih.gov/pubmed/33555378", "http://www.ncbi.nlm.nih.gov/pubmed/33130203", "http://www.ncbi.nlm.nih.gov/pubmed/29524445" ], "ideal_answer": [ "Favipiravir (FVP) has been used for treatment of COVID-19 in many countries." ], "exact_answer": [ "Covid-19", "influenza" ], "type": "factoid", "id": "621ebb733a8413c65300005c", "snippets": [ { "offsetInBeginSection": 125, "offsetInEndSection": 316, "text": ". In the COVID-19 era, there has been a race for drugs to be effective against SARS-CoV-2. There are reports about the uses of Remdesivir and Favipiravir as existing antivirals against virus ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535038", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 470, "text": "key repurposed drugs advocated to treat COVID-19 (lopinavir, ritonavir, ivermectin, remdesivir and favipiravir), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34497279", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 244, "text": ": To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34539392", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 254, "text": "Favipiravir (FPV) and hydroxychloroquine (HCQ) are considered possible COVID-19 treatments", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Favipiravir (FVP) has been used for treatment of COVID-19 in many countries. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34592006", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 134, "text": "To assess the efficacy of Favipiravir compared to the standard therapy in treating patients with severe COVID-19 infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34464921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Favipiravir versus standard of care in patients with severe COVID-19 infections", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34464921", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34571361", "endSection": "abstract" }, { "offsetInBeginSection": 1545, "offsetInEndSection": 1599, "text": "Molnupiravir/Favipiravir in the treatment of COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34571361", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 275, "text": "Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33746092", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Comparing ICU admission rates of mild/moderate COVID-19 patients treated with hydroxychloroquine, favipiravir, and hydroxychloroquine plus favipiravir.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33647553", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33191372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22429564", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "BACKGROUND: Favipiravir possesses high utility for treating patients with COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34044777", "endSection": "abstract" }, { "offsetInBeginSection": 450, "offsetInEndSection": 593, "text": "Favipiravir is active against a broad range of influenza viruses, including A(H1N1)pdm09, A(H5N1) and the recently emerged A(H7N9) avian virus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24084488", "endSection": "abstract" }, { "offsetInBeginSection": 692, "offsetInEndSection": 929, "text": "Favipiravir is approved in Japan for the treatment of influenza virus infections and has shown promise against other highly pathogenic RNA viruses including CCHFV with demonstrated efficacy in the type I interferon deficient mouse model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32645335", "endSection": "abstract" }, { "offsetInBeginSection": 293, "offsetInEndSection": 439, "text": "Favipiravir, an antiviral drug, is being used for COVID-19 treatment, and we currently have limited information regarding its efficacy and safety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33364790", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 460, "text": "Favipiravir is one such oral drug that was approved for new and reemerging pandemic influenza in Japan in 2014 and has shown potent in vitro activity against severe acute respiratory syndrome coronavirus-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33130203", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 274, "text": "Favipiravir is an antiviral previously indicated for influenza and Ebola, which has shown some promise in early trials for treatment of COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32405421", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 387, "text": "avipiravir, a novel antiviral drug which was mainly used for the treatment of influenza, now has been demonstrated to have a curative effect in treating Ebola virus infection. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28462833", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 362, "text": " so far. Favipiravir is a repurposed antiviral agent in treatment of SARS-CoV-2 infection, and to meet the current need, pharmaceutical companies are working for manufacturing licensed generic favi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33624584", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 352, "text": " demonstrate that Favipiravir [T-705, a drug in advanced clinical development for the treatment of infections with the influenza virus] inhibits in vitro murine norovirus replication. Tim", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22809499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The combination therapy of Lopinavir/Ritonavir plus Favipiravir might be a treatment option for patients with COVID-19", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33042544", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1000, "text": "vir, Favipiravir and Ribavirin might be a safer therapeutic option for COVID-19. Recent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33555378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548811", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "AIM: Favipiravir and oseltamivir are antiviral compounds used for the treatment of influenza infec", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24563658", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "WHAT IS KNOWN AND OBJECTIVE: Favipiravir is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34339547", "endSection": "abstract" }, { "offsetInBeginSection": 1108, "offsetInEndSection": 1313, "text": "Favipiravir is expected to be an important therapeutic agent for severe influenza, the next pandemic influenza strain, and other severe RNA virus infections for which standard treatments are not available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32097670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Favipiravir, also known as T-705, is an antiviral drug that has been approved in 2014 in Japan to treat pandemic influenza virus infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524445", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 544, "text": "Favipiravir (T-705) is a purine analogue antiviral approved for use in Japan against emerging influenza strains; and several phase 2 and 3 clinical trials are ongoing in the United States and Europe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29765101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Favipiravir as a potential countermeasure against neglected and emerging RNA viruses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29524445", "endSection": "title" }, { "offsetInBeginSection": 1416, "offsetInEndSection": 1623, "text": "With its unique mechanism of action and broad range of antiviral activity, favipiravir is a promising drug candidate for influenza and many other RNA viral diseases for which there are no approved therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24084488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Favipiravir has been developed as an anti-influenza drug and licensed as an anti-influenza drug in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32097670", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1072, "text": "Of note is that favipiravir shows anti-viral activities against other RNA viruses such as arenaviruses, bunyaviruses and filoviruses, all of which are known to cause fatal hemorrhagic fever.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28769016", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Favipiravir, an anti-influenza drug against life-threatening RNA virus infections.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32097670", "endSection": "title" } ] }, { "body": "Is MEDI2228 a bispecific antibody?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34301753" ], "ideal_answer": [ "No, MEDI2228 is an antibody drug conjugate (ADC)." ], "exact_answer": "no", "type": "yesno", "id": "62121c583a8413c653000016", "snippets": [ { "offsetInBeginSection": 135, "offsetInEndSection": 371, "text": "We here delineated the molecular and cellular mechanisms underlying novel immunomodulatory effects triggered by BCMA pyrrolobenzodiazepine (PBD) antibody drug conjugate (ADC) MEDI2228 which can augment efficacy of these immunotherapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34301753", "endSection": "abstract" } ] }, { "body": "Which syndrome is caused by pathogenic COL4A3-COL4A5 variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34245817", "http://www.ncbi.nlm.nih.gov/pubmed/34400539" ], "ideal_answer": [ "Massively parallel sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), 10% of those with kidney failure of unknown cause, and 20% with familial immunoglobulin A (IgA) glomerulonephritis. The population frequencies for Alport syndrome are suggested by the frequencies of predicted pathogenic COL4A3-COL4A5 variants, but must be adjusted for the disease penetrance of individual variants and for the likelihood of already diagnosed disease and non-Gly substitutions.", "Pathogenic variants in the genes in Alport Syndrome (COL4A3-C4A5) are found in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), and 20% with familial immunoglobulin A (IGA) Glomerulonephritis. The population frequencies for Alport syndrome are suggested to be higher than the frequencies of predicted pathogenic variants, but must be adjusted for the disease penetrance individual variants and for the likelihood of already diagnosed disease and non-Gly substitutions.", "Massively parallel sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), 10% of those with kidney failure of unknown cause, and 20% with familial immunoglobulin A (IgA) glomerulonephritis." ], "exact_answer": [ "Alport syndrome" ], "type": "factoid", "id": "61f56284882a024a10000005", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Pathogenic Variants in the Genes Affected in Alport Syndrome (COL4A3-COL4A5) and Their Association With Other Kidney Conditions: A Review", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34245817", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 318, "text": "Massively parallel sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), 10% of those with kidney failure of unknown cause, and 20% with familial immunoglobulin A (IgA) glomerulonephritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34245817", "endSection": "abstract" }, { "offsetInBeginSection": 1494, "offsetInEndSection": 1845, "text": "The population frequencies for Alport syndrome are suggested by the frequencies of predicted pathogenic COL4A3-COL4A5 variants, but must be adjusted for the disease penetrance of individual variants and for the likelihood of already diagnosed disease and non-Gly substitutions. Disease penetrance may depend on other genetic and environmental factors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34400539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "Massively parallel sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), 10% of those with kidney failure of unknown cause, and 20% with familial immunoglobulin A (IgA) glomerulonephritis. FSGS ass", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34245817", "endSection": "abstract" } ] }, { "body": "Is proton beam therapy used for treatment of craniopharyngioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27556661", "http://www.ncbi.nlm.nih.gov/pubmed/29404243", "http://www.ncbi.nlm.nih.gov/pubmed/32086697", "http://www.ncbi.nlm.nih.gov/pubmed/34078637", "http://www.ncbi.nlm.nih.gov/pubmed/29520496", "http://www.ncbi.nlm.nih.gov/pubmed/25260976", "http://www.ncbi.nlm.nih.gov/pubmed/32387488", "http://www.ncbi.nlm.nih.gov/pubmed/31860822", "http://www.ncbi.nlm.nih.gov/pubmed/32129277", "http://www.ncbi.nlm.nih.gov/pubmed/30257123", "http://www.ncbi.nlm.nih.gov/pubmed/25052561", "http://www.ncbi.nlm.nih.gov/pubmed/16580494", "http://www.ncbi.nlm.nih.gov/pubmed/16630407", "http://www.ncbi.nlm.nih.gov/pubmed/29459099", "http://www.ncbi.nlm.nih.gov/pubmed/24222710", "http://www.ncbi.nlm.nih.gov/pubmed/25487038", "http://www.ncbi.nlm.nih.gov/pubmed/30108004", "http://www.ncbi.nlm.nih.gov/pubmed/34049281", "http://www.ncbi.nlm.nih.gov/pubmed/26295365", "http://www.ncbi.nlm.nih.gov/pubmed/29932288" ], "ideal_answer": [ "Yes, proton beam therapy is used for treatment of craniopharyngioma." ], "exact_answer": "yes", "type": "yesno", "id": "601c4ff61cb411341a000022", "snippets": [ { "offsetInBeginSection": 1465, "offsetInEndSection": 1602, "text": " The majority of children had adjuvant therapy comprising proton beam therapy (18/59; 30.5%) or conventional radiotherapy (16/59; 27.1%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31860822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29459099", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29459099", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 328, "text": "MATERIALS AND METHODS: Between August 2013 and July 2016, 18 patients with craniopharyngiomas were treated with 54\u00a0Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at our centre.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29459099", "endSection": "abstract" }, { "offsetInBeginSection": 1142, "offsetInEndSection": 1261, "text": "CONCLUSIONS: Our early results are encouraging and comparable with the limited literature on PBT for craniopharyngioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29459099", "endSection": "abstract" }, { "offsetInBeginSection": 1902, "offsetInEndSection": 2048, "text": "All of the other patients underwent proton-beam radiotherapy with no documented tumor growth (median follow-up: 20 months; range 5.1-29.9\u00a0months).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29520496", "endSection": "abstract" }, { "offsetInBeginSection": 1673, "offsetInEndSection": 2110, "text": "Where aggressive subtotal resection is achieved, patients should be closely followed, with radiation initiated at the time of progression or recurrence-ideally via proton beam therapy, although three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and stereotactic radiosurgery are very appropriate in a range of circumstances, governed by access, patient age, disease architecture, and character of the recurrence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29404243", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 661, "text": " This study examined parental distress in a sample of families of patients with Cp treated with proton beam therapy to identify factors for targeting psychological intervention.PROCEDURE: Prior to (n\u00a0=\u00a096) and 1 year after (n\u00a0=\u00a073) proton therapy, parents of children diagnosed with Cp (9.81\u00a0\u00b1\u00a04.42 years at baseline; 49% male) completed a self-report measure of distress, the Brief Symptom Inventory (BSI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29932288", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 736, "text": "Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30108004", "endSection": "abstract" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1327, "text": "Initial experience with proton beam therapy in childhood-onset craniopharyngioma patients shows promising results in terms of more protective radiological treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30257123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24222710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Secondary neutron doses in proton therapy treatments of ocular melanoma and craniopharyngioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24222710", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29459099", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 789, "text": "LTS: Published reports suggest a benefit to proton beam therapy for use in tumors of the skull base, including craniopharyngiomas, chordomas, skull-base sarcomas, and unresectable meningiomas.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27556661", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 349, "text": "In recent years, proton therapy (PT), with its physical properties of heavy ion beam, that is, Prague peak phenomenon, has been more frequently used in patients with craniopharyngioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Proton beam therapy versus conformal photon radiation therapy for childhood craniopharyngioma: multi-institutional analysis of outcomes, cyst dynamics, and toxicity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25052561", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "PURPOSE: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25052561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Proton therapy for craniopharyngioma in adults: a protocol for systematic review and meta-analysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078637", "endSection": "title" }, { "offsetInBeginSection": 376, "offsetInEndSection": 584, "text": "We hereby report a case of a 7-year-old boy with a craniopharyngioma which had been subtotally resected and was subsequently treated with modern pencil beam proton therapy under high-precision image guidance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32129277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Pencil beam scanning proton therapy for the treatment of craniopharyngioma complicated with radiation-induced cerebral vasculopathies: A dosimetric and linear energy transfer (LET) evaluation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32387488", "endSection": "title" }, { "offsetInBeginSection": 1164, "offsetInEndSection": 1328, "text": "tial experience with proton beam therapy in childhood-onset craniopharyngioma patients shows promising results in terms of more protective radiological treatment. R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30257123", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "PURPOSE: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25052561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "BACKGROUND AND PURPOSE: This study analyses the dosimetric and dose averaged Linear Energy transfer (LETd) correlation in paediatric craniopharyngioma (CP) patients with and without radiation-induced cerebral vasculopathies (RICVs) treated with pencil beam scanning (PBS) pro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32387488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "OBJECTIVE: The authors compared survival and multiple comorbidities in children diagnosed with craniopharyngioma who underwent gross-total resection (GTR) versus subtotal resection (STR) with radiation therapy (RT), either intensity-modulated radiation therapy (IMRT) or proton beam therapy (P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34049281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29459099", "endSection": "title" }, { "offsetInBeginSection": 477, "offsetInEndSection": 571, "text": "s. Some studies have shown that PT has advantages in the treatment of craniopharyngioma in adu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Postoperative cerebral glucose metabolism in pediatric patients receiving proton therapy for craniopharyngioma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26295365", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Clinical equipoise: Protons and the child with craniopharyngioma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25487038", "endSection": "title" }, { "offsetInBeginSection": 198, "offsetInEndSection": 819, "text": "skull base. More public attention has been given to proton beam therapy due to the increasing number of centers now in operation or in the planning stages for offering this treatment option.METHODS: We reviewed the physical properties of protons and the clinical studies performed to justify their use in the management of skull-base tumors and determine the benefits of proton beam therapy.RESULTS: Published reports suggest a benefit to proton beam therapy for use in tumors of the skull base, including craniopharyngiomas, chordomas, skull-base sarcomas, and unresectable meningiomas.CONCLUSIONS: Use of proton beam th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27556661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "PURPOSE: We report the results of the early cohort of patients treated for craniopharyngioma with combined proton-photon irradiation at the Massachusetts General Hospital and the Harvard Cyclotron Laboratory.METHODS AND MATERIALS: Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or entirely with fractiona", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16580494", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "UNLABELLED: This retrospective preliminary review evaluated the efficacy and toxicity of fractionated proton radiotherapy in the management of pediatric craniopharyngioma.METHODS: Sixteen patients, aged 7-34 years, were treated with p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16630407", "endSection": "abstract" }, { "offsetInBeginSection": 323, "offsetInEndSection": 571, "text": "population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response.METHODS: We analyzed 14 adult patie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32086697", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 471, "text": "Proton radiation has been used safely and effectively for medulloblastoma, primitive neuro-ectodermal tumors, craniopharyngioma, ependymoma, germ cell intracranial tumors, low-grade glioma, retinoblastoma, rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma and other bone sarcomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25260976", "endSection": "abstract" }, { "offsetInBeginSection": 638, "offsetInEndSection": 1041, "text": "ontroversial. The purpose of this study was to evaluate the efficacy and safety of PT for craniopharyngioma in adults.METHODS AND ANALYSIS: We will search six databases (MEDLINE, EMBASE, Web of Science, the Cochrane Library, Amed, Scopus), clinical research registration websites and grey literature, aiming to identify randomised controlled trials (RCTs) on PT for craniopharyngioma in adults between 1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078637", "endSection": "abstract" } ] }, { "body": "What are the phases of hair follicle cycle?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30791955", "http://www.ncbi.nlm.nih.gov/pubmed/32615938", "http://www.ncbi.nlm.nih.gov/pubmed/32696520", "http://www.ncbi.nlm.nih.gov/pubmed/31415730", "http://www.ncbi.nlm.nih.gov/pubmed/31314901" ], "ideal_answer": [ "Hair follicle cycle phases (anagen, catagen and telogen)" ], "exact_answer": [ [ "anagen" ], [ "catagen" ], [ "telogen" ] ], "type": "list", "id": "606b30e094d57fd87900005f", "snippets": [ { "offsetInBeginSection": 305, "offsetInEndSection": 356, "text": " different HF stages (telogen, anagen, and catagen)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31415730", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 121, "text": "The signals that induce anagen (growth) in 'quiescent' human telogen hair follicles (HFs) are as yet unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31314901", "endSection": "abstract" }, { "offsetInBeginSection": 143, "offsetInEndSection": 199, "text": "hair follicle cycle phases (anagen, catagen and telogen)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32615938", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 284, "text": " hair follicle life-cycle transition from telogen to anagen phase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32696520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "The balance of Bmp6 and Wnt10b regulates the telogen-anagen transition of hair follicles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30791955", "endSection": "title" } ] }, { "body": "What is the cause of Bow Hunter's syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11795720", "http://www.ncbi.nlm.nih.gov/pubmed/26159645", "http://www.ncbi.nlm.nih.gov/pubmed/32068175", "http://www.ncbi.nlm.nih.gov/pubmed/12461405", "http://www.ncbi.nlm.nih.gov/pubmed/34764931", "http://www.ncbi.nlm.nih.gov/pubmed/26301025", "http://www.ncbi.nlm.nih.gov/pubmed/33552342", "http://www.ncbi.nlm.nih.gov/pubmed/25828501", "http://www.ncbi.nlm.nih.gov/pubmed/29018650", "http://www.ncbi.nlm.nih.gov/pubmed/32009470", "http://www.ncbi.nlm.nih.gov/pubmed/22608345", "http://www.ncbi.nlm.nih.gov/pubmed/16008165", "http://www.ncbi.nlm.nih.gov/pubmed/21769247", "http://www.ncbi.nlm.nih.gov/pubmed/9402591", "http://www.ncbi.nlm.nih.gov/pubmed/16485565", "http://www.ncbi.nlm.nih.gov/pubmed/31340945", "http://www.ncbi.nlm.nih.gov/pubmed/9120624", "http://www.ncbi.nlm.nih.gov/pubmed/16808831", "http://www.ncbi.nlm.nih.gov/pubmed/33476780", "http://www.ncbi.nlm.nih.gov/pubmed/27041076", "http://www.ncbi.nlm.nih.gov/pubmed/10845213", "http://www.ncbi.nlm.nih.gov/pubmed/28663954", "http://www.ncbi.nlm.nih.gov/pubmed/11859829", "http://www.ncbi.nlm.nih.gov/pubmed/32507079", "http://www.ncbi.nlm.nih.gov/pubmed/31570813", "http://www.ncbi.nlm.nih.gov/pubmed/27716015", "http://www.ncbi.nlm.nih.gov/pubmed/32983299", "http://www.ncbi.nlm.nih.gov/pubmed/24340230", "http://www.ncbi.nlm.nih.gov/pubmed/20959996" ], "ideal_answer": [ "Bow hunter's syndrome (BHS) is caused by posterior circulation insufficiency that results from the occlusion or compression of the vertebral artery (VA) during neck rotation.", "Bow Hunter's Syndrome (BHS) is caused by the occlusion of the vertebral artery with head rotation leading to ischemia and sometimes stroke." ], "type": "summary", "id": "60292d311cb411341a00010f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 166, "text": "Bow hunter's syndrome, or occlusion of the vertebral artery with head rotation leading to ischemia and sometimes stroke, is rarely described in children. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32507079", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 187, "text": "Bow hunter's syndrome (BHS) is caused by posterior circulation insufficiency that results from the occlusion or compression of the vertebral artery (VA) during neck rotation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32068175", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 110, "text": " Bow hunter's syndrome (BHS), also known as rotational vertebral artery occlusion syndrome, is rare", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32009470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Bow hunter's syndrome is characterized by transient vertebrobasilar insufficiency that is elicited by neck rotation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22608345", "endSection": "abstract" }, { "offsetInBeginSection": 902, "offsetInEndSection": 1024, "text": "Dissection of the contralateral (left) VA caused a failure in compensatory blood flow, resulting in bow hunter's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22608345", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 331, "text": "This mechanism of stroke has been reported as the Bow Hunter syndrome defined by vertebrobasilar insufficiency because of mechanical stenosis of the vertebral artery at the cervical level triggered by head movement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26159645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Vertebrobasilar insufficiency (VBI) provoked by physiological head rotation is known as rotational vertebral artery syndrome (RVAS) or Bow Hunter syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29018650", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Vertebrobasilar insufficiency (VBI) after rotation or hyperextension of the neck during otherwise routine activities is uncommon \"hairdresser syndrome\" (HDS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31570813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Rotational vertebral artery occlusion, also known as bow hunter's syndrome, is a well-documented surgically amenable cause of vertebrobasilar insufficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27041076", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Bow hunter's stroke results from vertebrobasilar insufficiency due to a mechanical occlusion or stenosis of the vertebral artery caused by head rotation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16485565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Bow hunter's stroke results from vertebrobasilar insufficiency caused by mechanical occlusion or stenosis of the vertebral artery (VA) at the C1-2 level on head rotation. S", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9120624", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Bow hunter's stroke results from vertebrobasilar insufficiency caused by mechanical occlusion or stenosis of the vertebral artery at the C 1-2 level on head rotation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10845213", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Bow Hunter's syndrome is extremely rare, which is mainly caused by mechanical vertebral artery occlusion or stenosis during head and neck rotation or hyperextension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32983299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "OBJECTIVE AND IMPORTANCE: Bow hunter's stroke is a consequence of vertebrobasilar insufficiency as a result of mechanical occlusion or stenosis of the vertebral artery at the C1-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9402591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "OBJECTIVE AND IMPORTANCE: Bow hunter's stroke is a symptomatic vertebrobasilar insufficiency caused by stenosis or occlusion of the vertebral artery at the C1C2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11859829", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Bow hunter's stroke (BHS) is a cerebrovascular disease caused by occlusion of the vertebral artery (VA) on head rotation. BHS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21769247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Bow hunter stroke, which is characterized by transient vertebrobasilar ischemia brought on by head turning, is an unusual condition usually caused by structural abnormalities at the craniocervical junction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11795720", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 318, "text": "mic stroke. This mechanism of stroke has been reported as the Bow Hunter syndrome defined by vertebrobasilar insufficiency because of mechanical stenosis of the vertebral artery at the cervical level triggered by h", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26159645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Bow Hunter's syndrome is an unusual symptomatic vertebrobasilar insufficiency resulting from intermittent mechanical compression of the vertebral artery, and is rarely a trigger for cerebral infarction following thrombus formation on the damaged endothelial vessels (Bow Hunter's stroke). T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28663954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Bow hunter's syndrome (BHS) is caused by transient vertebro-basilar ischemia on head rotation. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16808831", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 489, "text": "ildren. While there have been prior reports of this rare disorder, we describe an exceptional case of pediatric Bow Hunter's stroke resulting from a near complete occlusion the right vertebral artery (VA) secondary to an anomalous spur emanating from the right occipital con", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24340230", "endSection": "abstract" }, { "offsetInBeginSection": 411, "offsetInEndSection": 571, "text": "resented a case in which bow hunter's stroke was caused by occlusion of a non-dominant VA ending in the posterior inferior cerebellar artery (PICA). Diagnosis o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16008165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Rotational vertebrobasilar insufficiency, or bow hunter's syndrome, is a rare cause of posterior circulation ischemia, which, following rotation of the head, results in episodic vertigo, dizziness, nystagmus, or syncope. While t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27716015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "INTRODUCTION: Rotational vertebral artery occlusion (RVAO), sometimes known as \"Bow hunter syndrome,\" is an important and diagnostically challenging cause of posterior circulation stroke in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20959996", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "BACKGROUND: Bow Hunter's Syndrome is a mechanical occlusion of the vertebral artery which leads to a reduction in blood flow in posterior cerebral circulation resulting in transient reversible symptomatic vertebrobasilar insufficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26301025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Bow Hunter's syndrome (BHS) is a rare cause of vertebrobasilar insufficiency and is reported to most commonly be caused by vertebral artery impingement on cervical vertebrae osteophytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31340945", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Bow Hunter's syndrome, also referred to as rotational occlusion of the vertebral artery, is caused by dynamic compression of a patient's dominant vertebral artery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33552342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 396, "text": "BACKGROUND: Bow Hunter's Syndrome is a mechanical occlusion of the vertebral artery which leads to a reduction in blood flow in posterior cerebral circulation resulting in transient reversible symptomatic vertebrobasilar insufficiency.CASE DESCRIPTION: We present a case of Bow Hunter's syndrome in a 53-year-old male that occurred after the patient underwent surgical correction of a proximal le", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26301025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Rotational occlusion of the vertebral artery (VA), or bow hunter's syndrome, is a rare yet surgically treatable cause of vertebrobasilar insufficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25828501", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 487, "text": "ebral artery is involved. No case of bow hunter's stroke as a result of mechanical occlusion of a nondominant vertebral artery has ever been reported.CLINICAL PRESENTATION: We describe a rare case of Wallenberg's syndrome caused by occlusion of a nondo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9402591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Case Report: Bow Hunter's Syndrome Caused by Compression of Extracranially Originated Posterior Inferior Cerebellar Artery.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34764931", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Bow hunter's syndrome is due to vertebrobasilar insufficiency caused by rotational compression of the vertebral artery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33476780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Bow hunter's syndrome (BHS) is most commonly caused by compression of the vertebral artery (VA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34764931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "STUDY DESIGN: A case report.OBJECTIVE: To illustrate a rare case of bow hunter's syndrome in a patient with significant contralateral vertebral artery (VA) occlusive disease.SUMMARY OF BACKGROUND DATA: Bow hunter's syndrome is an uncommon condition in which the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12461405", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 288, "text": "Bow Hunter's syndrome is an unusual symptomatic vertebrobasilar insufficiency resulting from intermittent mechanical compression of the vertebral artery, and is rarely a trigger for cerebral infarction following thrombus formation on the damaged endothelial vessels (Bow Hunter's stroke).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28663954", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Bow hunter's syndrome in the setting of contralateral vertebral artery stenosis: evaluation and treatment options.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12461405", "endSection": "title" } ] }, { "body": "What types of anti-tumor therapeutic antibodies are available?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32370812" ], "ideal_answer": [ "Anti-tumor therapeutic antibodies include single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs)." ], "exact_answer": [ [ "single-targeted antibodies" ], [ "bi-specific antibodies", "BsAbs" ], [ "antibody-drug conjugates", "ADCs" ] ], "type": "list", "id": "621215ec3a8413c653000012", "snippets": [ { "offsetInBeginSection": 774, "offsetInEndSection": 1148, "text": "Therefore, when developing anti-tumor therapeutic antibodies, including single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs), many factors, such as target biology, cellular distribution of the targets, the environments of particular tumor types, as well as the proposed mechanism of action (MOA), must be taken into consideration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32370812", "endSection": "abstract" } ] }, { "body": "Which disease do pathogenic NR2F1 variants cause?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26986877" ], "ideal_answer": [ "Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal-dominant disorder characterized by optic atrophy and intellectual disability caused by loss-of-function mutations in NR2F1.", "Bosch-Boonstra-Schaaf optic atrophy syndrome", "Bosch-Boonstra-Schaaf Optic Atrophy Syndrome" ], "exact_answer": [ "Bosch-Boonstra-Schaaf optic atrophy syndrome", "BBSOAS" ], "type": "factoid", "id": "61f52f22882a024a10000002", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 202, "text": "Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal-dominant disorder characterized by optic atrophy and intellectual disability caused by loss-of-function mutations in NR2F1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26986877", "endSection": "abstract" } ] }, { "body": "Which mutation is targeted by Tepotinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34037224", "http://www.ncbi.nlm.nih.gov/pubmed/32469185", "http://www.ncbi.nlm.nih.gov/pubmed/33818908", "http://www.ncbi.nlm.nih.gov/pubmed/32702795", "http://www.ncbi.nlm.nih.gov/pubmed/32716573", "http://www.ncbi.nlm.nih.gov/pubmed/28024693", "http://www.ncbi.nlm.nih.gov/pubmed/33851690", "http://www.ncbi.nlm.nih.gov/pubmed/33533182", "http://www.ncbi.nlm.nih.gov/pubmed/32306194", "http://www.ncbi.nlm.nih.gov/pubmed/34590003", "http://www.ncbi.nlm.nih.gov/pubmed/34295201", "http://www.ncbi.nlm.nih.gov/pubmed/33335011", "http://www.ncbi.nlm.nih.gov/pubmed/33305187", "http://www.ncbi.nlm.nih.gov/pubmed/34295669", "http://www.ncbi.nlm.nih.gov/pubmed/33387444" ], "ideal_answer": [ "MET Exon 14 Skipping Mutation is targeted by Tepotinib that is used for patients with non-small-cell lung cancer." ], "exact_answer": [ "MET Exon 14 Skipping Mutation" ], "type": "factoid", "id": "6020b5681cb411341a000088", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "BACKGROUND: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469185", "endSection": "abstract" }, { "offsetInBeginSection": 1939, "offsetInEndSection": 2130, "text": "CONCLUSIONS: Among patients with advanced NSCLC with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32469185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306194", "endSection": "title" }, { "offsetInBeginSection": 757, "offsetInEndSection": 941, "text": "If type I MET inhibitors (crizotinib, capmatinib, tepotinib, savolitinib) drug resistance is developed, type II MET inhibitors (cabozantinib, glesatinib, merestinib) can be considered.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306194", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 336, "text": "Drugs targeting MET 14 exon skipping mutation bring new hope to patients. MET inhibitors that are currently on the market or are about to be marketed include: crizotinib, cabozantinib, savolitinib and tepotinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32702795", "endSection": "abstract" }, { "offsetInBeginSection": 853, "offsetInEndSection": 1040, "text": "At least five MET-targeted TKIs, including crizotinib, cabozantinib, capmatinib, tepotinib, and glesatinib, are being investigated clinically for patients with MET exon 14 altered-NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28024693", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 442, "text": "Tepotinib hydrochloride is an orally bioavailable, mesenchymal-epithelial transition (MET) TKI developed mainly for selected NSCLC patients with METex14 skipping mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33851690", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 362, "text": "hibitors for MET exon 14 skipping mutation such as capmatinib and tepotinib have elucidated their effectiveness. Only a few reports have suggested their efficacy ag", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Tepotinib is an oral MET inhibitor approved for metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33305187", "endSection": "abstract" }, { "offsetInBeginSection": 490, "offsetInEndSection": 692, "text": "ET exon 14 skipping mutation and poor performance status salvaged by marked leptomeningeal metastases response to tepotinib. We further provide measures of plasma/cerebrospinal fluid concentrations of t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene (MET) exon 14 skipping mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33387444", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 511, "text": "Herein, we report a case of a patient with metastatic lung adenocarcinoma harboring a MET exon 14 splice site mutation who has had prolonged disease control by a second-generation MET-TKI tepotinib. A 66-yr-old man was diagn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33335011", "endSection": "abstract" }, { "offsetInBeginSection": 385, "offsetInEndSection": 606, "text": "Recently, in METex14-mutated NSCLC, multitarget tyrosine kinase inhibitors (TKIs), such as crizotinib and cabozantinib, as well as MET-selective TKIs, such as tepotinib and capmatinib, have demonstrated durable responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32716573", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Tepotinib is an oral MET inhibitor approved for metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations. Ex", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33305187", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 210, "text": "(NSCLC). The MET inhibitor tepotinib has demonstrated clinical efficacy in patients with MET exon 14 skipp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34037224", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 704, "text": "ification (~14%). In 2020, the approval of two MET-tyrosine kinase inhibitors (TKIs), capmatinib and tepotinib, for NSCLCs carrying MET\u2206ex14 dawned a new era for ME", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34295201", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Recently approved and highly specific small-molecule inhibitors of c-MET exon 14 skipping mutations (e.g., capmatinib, tepotinib) are a new and important therapeutic option for the treatment of non-small cell lung cancer (NSCLC) patients harbouring c-MET alterations. Seve", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34295669", "endSection": "abstract" }, { "offsetInBeginSection": 393, "offsetInEndSection": 620, "text": ", in METex14-mutated NSCLC, multitarget tyrosine kinase inhibitors (TKIs), such as crizotinib and cabozantinib, as well as MET-selective TKIs, such as tepotinib and capmatinib, have demonstrated durable responses. In this study", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32716573", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 443, "text": "tudies reported that NSCLC patients harboring a METex14del responded well to MET-tyrosine kinase inhibitors (TKIs), including tepotinib. Tepotinib ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33533182", "endSection": "abstract" }, { "offsetInBeginSection": 873, "offsetInEndSection": 1064, "text": "rgeted TKIs, including crizotinib, cabozantinib, capmatinib, tepotinib, and glesatinib, are being investigated clinically for patients with MET exon 14 altered-NSCLC. A further two compounds ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28024693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene (MET) exon 14 skipping mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33387444", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 302, "text": ". Several tyrosine kinase inhibitors for MET exon 14 skipping mutation such as capmatinib and tepotinib have elucidated their effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590003", "endSection": "abstract" }, { "offsetInBeginSection": 1521, "offsetInEndSection": 1670, "text": "Tepotinib at this dose has obtained regulatory approval for the treatment of patients with non-small cell lung cancer harboring MET exon 14 skipping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33818908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Activity and bioavailability of tepotinib for leptomeningeal metastasis of NSCLC with MET exon 14 skipping mutation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33387444", "endSection": "title" }, { "offsetInBeginSection": 146, "offsetInEndSection": 407, "text": "Examining treatment-naive or tepotinib-resistant cells with MET amplification or METex14 skipping mutations identifies other receptor tyrosine kinases (RTKs) that co-exist in cells prior to tepotinib exposure and become more prominent upon tepotinib resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33305187", "endSection": "abstract" } ] }, { "body": "List second messengers.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32770509", "http://www.ncbi.nlm.nih.gov/pubmed/32441418", "http://www.ncbi.nlm.nih.gov/pubmed/32890866", "http://www.ncbi.nlm.nih.gov/pubmed/31789101", "http://www.ncbi.nlm.nih.gov/pubmed/31720987", "http://www.ncbi.nlm.nih.gov/pubmed/31710099", "http://www.ncbi.nlm.nih.gov/pubmed/31740493", "http://www.ncbi.nlm.nih.gov/pubmed/31744935", "http://www.ncbi.nlm.nih.gov/pubmed/31776060", "http://www.ncbi.nlm.nih.gov/pubmed/31804167", "http://www.ncbi.nlm.nih.gov/pubmed/31706224" ], "ideal_answer": [ "Cyclic adenosine monophosphate\nCeramide\nCyclic diguanylate\nNitric oxide\nCalcium\nDiacylglycerol" ], "exact_answer": [ [ "Cyclic adenosine monophosphate" ], [ "Ceramide" ], [ "Cyclic diguanylate" ], [ "Nitric oxide" ], [ "Calcium" ], [ "Diacylglycerol" ] ], "type": "list", "id": "6032874f1cb411341a000143", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Cyclic adenosine monophosphate (cAMP) is a second messenger involved in the dental regeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32441418", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 125, "text": "ceramide, a second messenger,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32770509", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 207, "text": "cAMP is a universal second messenger ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32890866", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 759, "text": "second messenger, cAMP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31706224", "endSection": "abstract" }, { "offsetInBeginSection": 25, "offsetInEndSection": 71, "text": "second messenger cyclic diguanylate (c-di-GMP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31740493", "endSection": "abstract" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1235, "text": "nitric oxide (NO) as a second messenger", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31720987", "endSection": "abstract" }, { "offsetInBeginSection": 3, "offsetInEndSection": 28, "text": " second messenger calcium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31744935", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 389, "text": "Diacylglycerol (DAG) is a critical second messenger", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31710099", "endSection": "abstract" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1008, "text": " second messenger cyclic diguanylate (c-di-GMP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31789101", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 972, "text": "second messenger of neurotransmitter like nitric oxide (NO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31804167", "endSection": "abstract" }, { "offsetInBeginSection": 118, "offsetInEndSection": 173, "text": "second messenger cyclic adenosine monophosphate (cAMP),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776060", "endSection": "abstract" } ] }, { "body": "Is there a genetic cause of craniostenosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29579021", "http://www.ncbi.nlm.nih.gov/pubmed/3221205", "http://www.ncbi.nlm.nih.gov/pubmed/15791470", "http://www.ncbi.nlm.nih.gov/pubmed/29037998", "http://www.ncbi.nlm.nih.gov/pubmed/7400783", "http://www.ncbi.nlm.nih.gov/pubmed/964994", "http://www.ncbi.nlm.nih.gov/pubmed/11977182", "http://www.ncbi.nlm.nih.gov/pubmed/26463893", "http://www.ncbi.nlm.nih.gov/pubmed/28523332", "http://www.ncbi.nlm.nih.gov/pubmed/19893477" ], "ideal_answer": [ "9There a a number of different genetic mutations or syndromes(Saethre-Chotzen, Aperts, Crouzon, Pfeiffer) associated with craniostenosis.", "Saethre-Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities" ], "exact_answer": "yes", "type": "yesno", "id": "601d73261cb411341a00003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb \"in delta\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28523332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "A 3-year-old child with tertiary trisomy (14 (+14q--), daughter of a mother with a balanced reciprocal translocation [46,XX,t(14;16)(q11;q24) is presented. Craniostenosis and developmental retardation were the primary presenting features in this patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/964994", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Saethre-Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11977182", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 452, "text": ". For 98 patients (15%) a syndrome is associated. Third part of them has Apert syndrome, an other third part has Crouzon syndrome, and for the last third more exceptional acrocephalosyndactyly syndrome (Saethre-Chotzen, Pfeiffer) or others atypical associations, sometimes not yet described, but with an autosomal dominant inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3221205", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 786, "text": "Coronal craniostenosis seems to be a dominant autosomal character, when scaphocephaly is more often sporadic; for both, an autosomal dominant inheritance is not excluded for some pedigrees.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3221205", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 537, "text": " genetic origins are not completely clear although mutations in the genes that code for fibroblast growth factor receptors have been described; depending upon the gene involved, the type of mutation and the embryological period in which the mutation itself occurs, a type of craniosynostosis arises that may involve one or more cranial sutures. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19893477", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Saethre-Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11977182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Identification and analysis of the genetic causes in nine unrelated probands with syndromic craniosynostosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29037998", "endSection": "title" }, { "offsetInBeginSection": 144, "offsetInEndSection": 438, "text": "To identify and analyze causative genetic variants in nine unrelated probands mainly manifested as syndromic craniosynostosis, we reviewed the relevant medical information of the patients and performed the whole exome sequencing, further verified with Sanger sequencing and parental background.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29037998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "[Genetic counseling in craniostenosis. Results of a prospective study performed with a group of studies on craniofacial malformations].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3221205", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Constitutional 11q interstitial deletion syndrome presents with congenital anomalies including microcephaly with craniostenosis, minor dysmorphic features, vitreoretinopathy, and renal anomalies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26463893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "A suckling baby with microcephaly, craniostenosis, downward slanting palpebral fissues, malformed ears, cerebral, cardiac and intestinal malformation, and partial 6q25 leads to 6qter trisomy is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7400783", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 533, "text": "Its genetic origins are not completely clear although mutations in the genes that code for fibroblast growth factor receptors have been described; depending upon the gene involved, the type of mutation and the embryological period in which the mutation itself occurs, a type of craniosynostosis arises that may involve one or more cranial sutures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19893477", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1421, "text": "through which skull growth abnormalities are seen. It is becoming clearer that in most patients with craniosynostosis, there is regional imbalance of skull growth, which co-exists with a variety of other equally important factors, such as genetic defects, raised intracranial pressure, venous hypertension, and other brain parenchymal a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15791470", "endSection": "abstract" }, { "offsetInBeginSection": 1389, "offsetInEndSection": 1692, "text": "Recent genetic studies have identified several novel genes and pathways that cause nonsyndromic craniosynostosis, providing genetic evidence linking the causes of syndromic and nonsyndromic craniosynostoses, and allowing for genotype-based prediction of risk of recurrence in some nonsyndromic families.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29579021", "endSection": "abstract" } ] }, { "body": "Can bergapten cross the blood-brain barrier?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34347307" ], "ideal_answer": [ "Yes, bergapten can cross the blood-brain barrier." ], "exact_answer": "yes", "type": "yesno", "id": "620586a8c9dfcb9c09000032", "snippets": [ { "offsetInBeginSection": 449, "offsetInEndSection": 739, "text": "Moreover, pharmacokinetic studies showed that bergapten has higher absolute bioavailability and can cross the blood-brain barrier and has a great potential for treating brain disease, but the mechanism needs further clarification to make greater use of its ability to treat brain diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34347307", "endSection": "abstract" } ] }, { "body": "Does TIMELESS-TIPIN participate in replisome disassembly?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34269473" ], "ideal_answer": [ "Yes. TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans." ], "exact_answer": "yes", "type": "yesno", "id": "620be4fd3a8413c653000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34269473", "endSection": "title" }, { "offsetInBeginSection": 729, "offsetInEndSection": 1125, "text": "We show that UBXN-3 is important in\u00a0vivo for replisome disassembly in the absence of TIMELESS-TIPIN. Correspondingly, co-depletion of UBXN-3 and TIMELESS causes profound synthetic lethality. Since the human orthologue of UBXN-3, FAF1, is a candidate tumour suppressor, these findings suggest that manipulation of CMG disassembly might be applicable to future strategies for treating human cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34269473", "endSection": "abstract" } ] }, { "body": "Nemolizumab has been shown to be effective for which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33735876", "http://www.ncbi.nlm.nih.gov/pubmed/34213742", "http://www.ncbi.nlm.nih.gov/pubmed/32507066", "http://www.ncbi.nlm.nih.gov/pubmed/29753033", "http://www.ncbi.nlm.nih.gov/pubmed/28703903", "http://www.ncbi.nlm.nih.gov/pubmed/32640132", "http://www.ncbi.nlm.nih.gov/pubmed/33045848", "http://www.ncbi.nlm.nih.gov/pubmed/34726262", "http://www.ncbi.nlm.nih.gov/pubmed/31449914", "http://www.ncbi.nlm.nih.gov/pubmed/33924978", "http://www.ncbi.nlm.nih.gov/pubmed/33644104", "http://www.ncbi.nlm.nih.gov/pubmed/28249150", "http://www.ncbi.nlm.nih.gov/pubmed/32074418", "http://www.ncbi.nlm.nih.gov/pubmed/33711179" ], "ideal_answer": [ "Nemolizumab has been shown to be effective for atopic dermatitis." ], "exact_answer": [ "atopic dermatitis" ], "type": "factoid", "id": "602354e41cb411341a000098", "snippets": [ { "offsetInBeginSection": 631, "offsetInEndSection": 759, "text": "Dupilumab, lebrikizumab, and nemolizumab demonstrate efficacy as agents producing improvement in clinical severity and pruritus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33045848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31449914", "endSection": "title" }, { "offsetInBeginSection": 1696, "offsetInEndSection": 1876, "text": "CONCLUSIONS: Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30\u00a0mg. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31449914", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 972, "text": "Lebrikizumab, tralokinumab, fezakinumab, nemolizumab, and GBR 830 lead to statistically significant improvements in disease severity and multiple endpoint outcome scores. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32507066", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1485, "text": "Tralokinumab, lebrikizumab, fezakinumab, nemolizumab, and GBR 830 are effective treatment options for adults with moderate-to-severe AD, but further large-scale studies are needed to confirm their efficacy as monotherapy in children with moderate-to-severe AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32507066", "endSection": "abstract" }, { "offsetInBeginSection": 1795, "offsetInEndSection": 2110, "text": "CONCLUSIONS: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32074418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132", "endSection": "title" }, { "offsetInBeginSection": 191, "offsetInEndSection": 266, "text": "In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132", "endSection": "abstract" }, { "offsetInBeginSection": 2054, "offsetInEndSection": 2256, "text": "CONCLUSIONS: In this 16-week trial, the use of subcutaneous nemolizumab in addition to topical agents for atopic dermatitis resulted in a greater reduction in pruritus than placebo plus topical agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132", "endSection": "abstract" }, { "offsetInBeginSection": 557, "offsetInEndSection": 726, "text": "Recent clinical trials have shown that the anti-IL-31RA antibody nemolizumab can successfully decrease pruritus in patients with atopic dermatitis and prurigo nodularis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33924978", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1199, "text": "Tralokinumab, lebrikizumab, and nemolizumab have also been confirmed to have significant efficacy against AD in phase III or IIb clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34213742", "endSection": "abstract" }, { "offsetInBeginSection": 1863, "offsetInEndSection": 1990, "text": "s showed nemolizumab could be another alternative therapy for moderate-to-severe AD with long-term efficiency and safety.CONCLU", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33735876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Nemolizumab is a humanized anti-interleukin-31 receptor A monoclonal antibody for treating atopic dermatitis, and it especially improves pruritus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28703903", "endSection": "abstract" }, { "offsetInBeginSection": 264, "offsetInEndSection": 553, "text": "ecently, Interleukin (IL)-31 and its receptor complex attracted significant interest, as clinical phase two studies demonstrated therapeutic efficacy of the neutralizing IL-31 receptor A (IL-31RA) antibody nemolizumab in patients suffering from atopic dermatitis or prurigo nodularis. IL-3", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33644104", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 737, "text": "cal trials have shown that the anti-IL-31RA antibody nemolizumab can successfully decrease pruritus in patients with atopic dermatitis and prurigo nodularis. The IL-31 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33924978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "BACKGROUND: Nemolizumab, an anti-IL-31 receptor A\u00a0mAb, improved pruritus, dermatitis, and sleep in adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments in a phase II, 12-week, randomized, double-blind, placebo-controlled study (part A; NCT01986", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753033", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 312, "text": "ritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34726262", "endSection": "abstract" }, { "offsetInBeginSection": 1082, "offsetInEndSection": 1228, "text": "and nemolizumab have also been confirmed to have significant efficacy against AD in phase III or IIb clinical trials. Also, fezakinumab was effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34213742", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 607, "text": "n pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration period.OBJECTIVE: To examine the long-term effectiveness and safety of nemolizumab in patients aged \u226513 years with AD and inadequately controlled moderate-to-severe pruritus.METHODS: In two long-term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34726262", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "BACKGROUND: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD).OBJECTIVE: Analyse onset of action of nemolizumab 30\u00a0mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD.METHODS: Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores\u00a0\u2265\u00a016 from a phase 2b", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33711179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 580, "text": "BACKGROUND: Nemolizumab, an anti-IL-31 receptor A\u00a0mAb, improved pruritus, dermatitis, and sleep in adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments in a phase II, 12-week, randomized, double-blind, placebo-controlled study (part A; NCT01986933).OBJECTIVE: We sought to assess the long-term efficacy and safety of nemolizumab injected subcutaneously every 4\u00a0weeks (Q4W) or every 8\u00a0weeks (Q8W) in a 52-week, double-blind extension (part B).METHODS: During part B, patients continued the previous nemolizumab dose (0.1, 0.5, or ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753033", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 659, "text": "d pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis.METHODS: In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per ki", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28249150", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 473, "text": "BACKGROUND: Nemolizumab targets the IL-31 receptor \u03b1 subunit involved in atopic dermatitis (AD) pathogenesis.OBJECTIVE: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD.METHODS: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90\u00a0mg) subcutaneous injections every 4\u00a0weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31449914", "endSection": "abstract" }, { "offsetInBeginSection": 179, "offsetInEndSection": 567, "text": "dermatitis. In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis.METHODS: In a 16-week, double-blind, phase 3 trial, we randomly assigned Japanese patients with atopic dermatitis and moderate-to-severe pruritus and an inadequate response to topical agents in a 2:1 ratio to receive subcutaneous nemolizumab (60 mg) or placebo every 4 weeks until week 16, with concom", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32640132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Nemolizumab is associated with a rapid improvement in atopic dermatitis signs and symptoms: subpopulation (EASI\u00a0\u2265\u00a016) analysis of randomized phase 2B study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33711179", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Nemolizumab plus topical agents in patients with atopic dermatitis and moderate-to-severe pruritus provide improvement in pruritus and signs of atopic dermatitis for up to 68\u00a0weeks: results from two phase III, long-term studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34726262", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Nemolizumab in patients with moderate-to-severe atopic dermatitis: Randomized, phase II, long-term extension study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29753033", "endSection": "title" }, { "offsetInBeginSection": 1435, "offsetInEndSection": 1814, "text": " maintained during the follow-up period. The long-term safety profile was consistent with previous studies, with no unexpected late-onset adverse events.CONCLUSIONS: Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate-to-severe pruritus produced a continuous improvement in pruritus, signs of AD, and quality of life", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34726262", "endSection": "abstract" } ] }, { "body": "Is hemoglobin antimicrobial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32050591", "http://www.ncbi.nlm.nih.gov/pubmed/32504846", "http://www.ncbi.nlm.nih.gov/pubmed/31491713" ], "ideal_answer": [ "Yes,\nBeyond its physiological activity, hemoglobins are able to inhibit the growth of several microorganisms." ], "exact_answer": "yes", "type": "yesno", "id": "60570fe494d57fd879000026", "snippets": [ { "offsetInBeginSection": 172, "offsetInEndSection": 313, "text": "the \u03b1137-141 peptide, a natural antimicrobial peptide, can be obtained after hydrolysis of hemoglobin, the main constituent of blood red part", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31491713", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 173, "text": "Beyond its physiological activity, hemoglobins are able to inhibit the growth of several microorganisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32050591", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 574, "text": "A novel AMP, T. granosa hemoglobin-derived peptide (TGH1), was identified and its antimicrobial effect", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32504846", "endSection": "abstract" } ] }, { "body": "What is the mammalian version of arginine vasotocin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16005652", "http://www.ncbi.nlm.nih.gov/pubmed/11423156", "http://www.ncbi.nlm.nih.gov/pubmed/26129685", "http://www.ncbi.nlm.nih.gov/pubmed/192600", "http://www.ncbi.nlm.nih.gov/pubmed/18330923", "http://www.ncbi.nlm.nih.gov/pubmed/25997523", "http://www.ncbi.nlm.nih.gov/pubmed/19341739", "http://www.ncbi.nlm.nih.gov/pubmed/11467881", "http://www.ncbi.nlm.nih.gov/pubmed/28288796", "http://www.ncbi.nlm.nih.gov/pubmed/10848505", "http://www.ncbi.nlm.nih.gov/pubmed/22802939", "http://www.ncbi.nlm.nih.gov/pubmed/19576218", "http://www.ncbi.nlm.nih.gov/pubmed/28855890", "http://www.ncbi.nlm.nih.gov/pubmed/26739197", "http://www.ncbi.nlm.nih.gov/pubmed/19018131", "http://www.ncbi.nlm.nih.gov/pubmed/27940222", "http://www.ncbi.nlm.nih.gov/pubmed/18174156", "http://www.ncbi.nlm.nih.gov/pubmed/24107293", "http://www.ncbi.nlm.nih.gov/pubmed/22906877", "http://www.ncbi.nlm.nih.gov/pubmed/28824546" ], "ideal_answer": [ "Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP)", "Arginine vasopressin (AVP) is the mammalian homolog of arginine vasotocin (AVT)." ], "exact_answer": [ "Arginine vasopressin (AVP)" ], "type": "factoid", "id": "603bc3181cb411341a00015c", "snippets": [ { "offsetInBeginSection": 101, "offsetInEndSection": 336, "text": " Conopressin-T belongs to the vasopressin-like peptide family and displays high sequence homology to the mammalian hormone oxytocin (OT) and to vasotocin, the endogenous vasopressin analogue found in teleost fish, the cone snail's prey", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18174156", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 313, "text": "In particular, arginine vasopressin and its non-mammalian homolog, arginine vasotocin (AVT), have been implicated in regulating affiliative, reproductive, and aggressive behavior in many vertebrate species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28855890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28824546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The nonapeptides isotocin (IT) and arginine vasotocin (AVT), along with their mammalian homologs oxytocin and arginine vasopressin, are well known regulators of social behaviors across vertebrate taxa.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28288796", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The avian homologs of arginine vasopressin (AVP) and oxytocin (OT) are arginine vasotocin (AVT) and mesotocin (MT), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16005652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog arginine vasopressin, influence a wide range of physiological and behavioral responses, including aspects of sexual and social behaviors, osmoregulation, stress response, metabolism, blood pressure, and circadian rhythms. Here, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18330923", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1096, "text": "ic neuropeptide arginine-vasotocin (AVT) and its mammalian homologue, arginine- vasopressin (AVP) are key modulators of social behavior across vertebrates. In this study, we ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27940222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "The nonapeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin are well known for their role in the modulation of several intraspecific social behaviours, such as social approach/withdrawal and aggression. R", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "The neuropeptide arginine vasotocin (AVT; non-mammals) and its mammalian homologue, arginine vasopressin (AVP) influence a variety of sex-typical and species-specific behaviors, and provide an integrational neural substrate for the dynamic modulation of those behaviors by endocrine and sensory stimuli. Alth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11423156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The nonapeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin play a key role in the regulation of social behaviour across vertebrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25997523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "The neuropeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) are neuromodulators known to be steroid sensitive and associated with social behaviors in a number of vertebrate taxa. Ho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19018131", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Arginine vasotocin (VT), and its mammalian homologue arginine vasopressin (VP), are neuropeptides involved in the regulation of social behaviors and stress responsiveness. Pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19341739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Arginine vasotocin (AVT) and its mammalian homologue, arginine vasopressin (AVP), regulate a variety of social and reproductive behaviors, often with complex species-, sex- and context-dependent effects. Despit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906877", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 713, "text": "Among adult mammals arginine-vasotocin is replaced by arginine-vasopressin which has much less oxytocin activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/192600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP) and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28824546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Arginine vasotocin (VT), and its mammalian homologue arginine vasopressin (VP), are neuropeptides involved in the regulation of social behaviors and stress responsiveness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19341739", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Arginine vasotocin (AVT) and its mammalian homologue, arginine vasopressin (AVP), regulate a variety of social and reproductive behaviors, often with complex species-, sex- and context-dependent effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22906877", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Arginine vasotocin (AVT) and the mammalian homologue, arginine vasopressin (AVP), modulate vertebrate social behaviors, including vocalizations in male anurans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26129685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The nonapeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin are well known for their role in the modulation of several intraspecific social behaviours, such as social approach/withdrawal and aggression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24107293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Arginine vasotocin (AVT) and its mammalian homologoue arginine vasopressin (AVP) influence male sexual and aggressive behaviors in many species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11467881", "endSection": "abstract" }, { "offsetInBeginSection": 640, "offsetInEndSection": 970, "text": "Here we provide the first empirical evidence that arginine vasotocin (AVT), a non-mammalian homologue of arginine vasopressin (AVP), plays a critical role as moderator of interspecific behaviour in the best studied and ubiquitous marine cleaning mutualism involving the Indo-Pacific bluestreak cleaner wrasse Labroides dimidiatus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22802939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "The neurohypophysial peptide arginine vasotocin (AVT) and its mammalian ortholog arginine vasopressin function in a wide range of physiological and behavioral events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26739197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 297, "text": "The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog arginine vasopressin, influence a wide range of physiological and behavioral responses, including aspects of sexual and social behaviors, osmoregulation, stress response, metabolism, blood pressure, and circadian rhythms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18330923", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Arginine vasotocin (AVT) is a nonmammalian analog of the mammalian hormone arginine vasopressin (AVP).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10848505", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The nonapeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin play a key role in the regulation of social behaviour across vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25997523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "The peptide hormone arginine vasotocin (AVT) and its mammalian homolog arginine vasopressin modulate a variety of social behaviors in vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19576218", "endSection": "abstract" } ] }, { "body": "Which kinase does PD98059 inhibit?", "_type": "factoid", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32378175" ], "_body": "Which kinase does ??? inhibit?", "ideal_answer": [ "PD98059 is a specific, reversible MEK inhibitor." ], "exact_answer": [ "MEK" ], "type": "factoid", "id": "6206bf3cc9dfcb9c0900003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "An injectable microparticle formulation for the sustained release of the specific MEK inhibitor PD98059: in vitro evaluation and pharmacokinetics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32378175", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "PD98059 is a reversible MEK inhibitor that we are investigating as a potential treatment for neurochemical changes in the brain that drive neurohumoral excitation in heart failure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32378175", "endSection": "abstract" } ] }, { "body": "What is caused by loss-of-function variants in BCAS3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34022130" ], "ideal_answer": [ "Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder. BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis.", "Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder.", "BCAS3 microtubule-associated migration factor (BCAS3) is a large, highly tuned cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in the growth of tumors. It has been linked to a syndromic neurodevelopmental disorder.", "BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis. Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder." ], "exact_answer": [ "A syndromic neurodevelopmental disorder" ], "type": "factoid", "id": "61f80e22882a024a1000003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34022130", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis. Here, we established BCAS3 loss-of-function variants as causative for a neurodevelopmental disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34022130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34022130", "endSection": "title" } ] }, { "body": "Which transporter is inhibited by Sotagliflozin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31064765", "http://www.ncbi.nlm.nih.gov/pubmed/30819210", "http://www.ncbi.nlm.nih.gov/pubmed/33108240", "http://www.ncbi.nlm.nih.gov/pubmed/29916741", "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "http://www.ncbi.nlm.nih.gov/pubmed/29212386", "http://www.ncbi.nlm.nih.gov/pubmed/31172412", "http://www.ncbi.nlm.nih.gov/pubmed/32717480", "http://www.ncbi.nlm.nih.gov/pubmed/33413413", "http://www.ncbi.nlm.nih.gov/pubmed/28387957", "http://www.ncbi.nlm.nih.gov/pubmed/29637608", "http://www.ncbi.nlm.nih.gov/pubmed/31468649", "http://www.ncbi.nlm.nih.gov/pubmed/31837264", "http://www.ncbi.nlm.nih.gov/pubmed/29937430", "http://www.ncbi.nlm.nih.gov/pubmed/34106300", "http://www.ncbi.nlm.nih.gov/pubmed/32567125", "http://www.ncbi.nlm.nih.gov/pubmed/25690134", "http://www.ncbi.nlm.nih.gov/pubmed/33289297", "http://www.ncbi.nlm.nih.gov/pubmed/31850616", "http://www.ncbi.nlm.nih.gov/pubmed/33179277", "http://www.ncbi.nlm.nih.gov/pubmed/28899222", "http://www.ncbi.nlm.nih.gov/pubmed/31761990", "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "http://www.ncbi.nlm.nih.gov/pubmed/34232488", "http://www.ncbi.nlm.nih.gov/pubmed/31942549" ], "ideal_answer": [ "Sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2." ], "exact_answer": [ [ "sodium-glucose co-transporter 1" ], [ "sodium-glucose co-transporter 2" ] ], "type": "list", "id": "601c287f1cb411341a000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "CONTEXT: The effect of sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31837264", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 967, "text": "The potential of this method is showcased by the preparation and diversification of sotagliflozin, leading to the discovery of a promising SGLT2 inhibitor candidate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31850616", "endSection": "abstract" }, { "offsetInBeginSection": 824, "offsetInEndSection": 1215, "text": "Compared with metformin at Week 24 to 26, the SGLT inhibitors dapagliflozin (5 mg), sotagliflozin (200\u2009mg) and empagliflozin (10 mg) had larger reductions in HbA1c (mean difference [MD] = -0.24, 95% credible interval [CrI], -0.41 to -0.07, MD = -0.23, 95% CrI, -0.39 to -0.08 and MD = -0.35, 95% CrI, -0.51 to -0.19, respectively) and in weight, which were sustained in sensitivity analyses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31468649", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 749, "text": " Global trials have been conducted with liraglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and sotagliflozin, an inhibitor of both SGLT1 and SGLT2 transporters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32567125", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1399, "text": "Several SGLT2 inhibitors and their derivatives such as remogliflozin etabonate (phase-II), sotagliflozin (phase-III) and bexagliflozin (phase-III) are under different phases of clinical trial studies and some have been patented. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32717480", "endSection": "abstract" }, { "offsetInBeginSection": 320, "offsetInEndSection": 452, "text": "Sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, has been recently approved for use in patients with T1DM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33108240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 260, "text": "Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI \u226527\u00a0kg/m2 . ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33179277", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 490, "text": "Several clinical trials have shown that sotagliflozin (SGLT1-1/2 inhibitor) decreases body weight and reduces blood pressure in adults with T2D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31942549", "endSection": "abstract" }, { "offsetInBeginSection": 1036, "offsetInEndSection": 1222, "text": "ite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies. Whi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 866, "text": "Sotagliflozin appeared more promising for SGLT2 as well as AChE-inhibition with reference to \u0394G and Ki values in comparison to Ertugliflozin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28387957", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 600, "text": "Sotagliflozin is an oral potent dual inhibitor of the insulin-independent SGLT1 and SGLT2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29916741", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 606, "text": "EAS COVERED: Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor. O", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 668, "text": "Therefore, sotagliflozin (LX4211) has been developed as a dual inhibitor of SGLT1 and SGLT2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25690134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Sotagliflozin (Zynquista\u2122) is a dual inhibitor of sodium-glucose co-transporters (SGLT) 1 and 2 being developed by Lexicon Pharmaceuticals and Sanofi as a treatment for type 1 (T1DM) and type 2 diabetes mellitus (T2DM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31172412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Sotagliflozin (Zynquista\u2122) is the first dual inhibitor of sodium-glucose co-transporter-1 and -2 (SGLT1 and 2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31761990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25690134", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Sotagliflozin is a dual sodium-glucose co-transporter (SGLT) 2 inhibitor, manifesting a 20-fold higher inhibitory activity for SGLT2 than for SGLT1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34232488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Sotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30819210", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 749, "text": "Global trials have been conducted with liraglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and sotagliflozin, an inhibitor of both SGLT1 and SGLT2 transporters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32567125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Sotagliflozin is a dual sodium-glucose co-transporter (SGLT) 2 inhibitor, manifesting a 20-fold higher inhibitory activity for SGLT2 than for SGLT1. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34232488", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "INTRODUCTION: Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for u", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29212386", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "AIMS: To evaluate the evidence for the novel dual sodium-glucose co-transporter-1 (SGLT1) and -2 (SGLT2) inhibitor, sotagliflozin, which may enhance the efficacy of SGLT2 inhibitors by additionally reducing intestinal glucose absorption", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29637608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Sotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D). So", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30819210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "OBJECTIVE: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29937430", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 446, "text": "ation. Sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, has been recently approved for use in patients with", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33108240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Sotagliflozin, a dual sodium-glucose co-transporter (SGLT)1/SGLT2 inhibitor, is currently approved in Europe as an adjunct to optimal insulin therapy in adults with type 1 diabetes (T1D) and a body mass index (BMI) \u2265\u200927\u2009kg/m2 . In ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33289297", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 767, "text": "ls have been conducted with liraglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and sotagliflozin, an inhibitor of both SGLT1 and SGLT2 transporters. While dapaglifloz", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32567125", "endSection": "abstract" }, { "offsetInBeginSection": 446, "offsetInEndSection": 686, "text": "ion. We investigated the effects of chronic treatment with the dual SGLT-1&2 inhibitor sotagliflozin on left atrial (LA) remodeling and cellular arrhythmogenesis (i.e. atrial cardiomyopathy) in a metabolic syndrome-related rat model of HFpE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33413413", "endSection": "abstract" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1573, "text": "lc5a1) and Sglt2 (also known as Slc5a2) knockout mice were employed to develop sotagliflozin, a dual SGLT1/SGLT2 inhibitor having success in clinical trials for diabe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31064765", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 486, "text": " the DAPA-CKD study and the SCORED study two different sodium-glucose linked transporter 2 (SGLT2) inhibitors (dapagliflozin and sotagliflozin) were found to improve the prognosis of patients with chronic kidney diseases with and without diabetes. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34106300", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 677, "text": "re, sotagliflozin (LX4211) has been developed as a dual inhibitor of SGLT1 and SGLT2. The diff", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25690134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30819210", "endSection": "title" }, { "offsetInBeginSection": 148, "offsetInEndSection": 438, "text": "Sotagliflozin inhibits renal sodium-glucose co-transporter 2 (determining significant excretion of glucose in the urine, in the same way as other, already available SGLT-2 selective inhibitors) and intestinal SGLT-1, delaying glucose absorption and therefore reducing post prandial glucose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30819210", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Sotagliflozin, a dual sodium-glucose co-transporter (SGLT)1/SGLT2 inhibitor, is currently approved in Europe as an adjunct to optimal insulin therapy in adults with type 1 diabetes (T1D) and a body mass index (BMI) \u2265\u200927\u2009kg/m2 .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33289297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Sotagliflozin: a dual sodium-glucose co-transporter-1 and -2 inhibitor for the management of Type 1 and Type 2 diabetes mellitus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29637608", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 918, "text": "OBJECTIVE: To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes.RESEARCH DESIGN AND METHODS: We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment.RESULTS: In the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% (P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring (CGM) of 148.8 mg/dL (8.3 mmol/L) (P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) (P = 0.002) in HbA1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3 mg/dL (9.5 mmol/L), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26049551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "AIMS: To evaluate the evidence for the novel dual sodium-glucose co-transporter-1 (SGLT1) and -2 (SGLT2) inhibitor, sotagliflozin, which may enhance the efficacy of SGLT2 inhibitors by additionally reducing intestinal glucose absorption.METHODS: The search terms 'sotagliflozin', 'LX4211', 'SGLT' and 'diabetes' were enter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29637608", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Efficacy and safety of adding sotagliflozin, a dual sodium-glucose co-transporter (SGLT)1 and SGLT2 inhibitor, to optimized insulin therapy in adults with type 1 diabetes and baseline body mass index \u2265\u200927\u2009kg/m2.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33289297", "endSection": "title" }, { "offsetInBeginSection": 109, "offsetInEndSection": 575, "text": "rapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes.METHODS: In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28899222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 504, "text": "CONTEXT: The effect of sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans.OBJECTIVE: To measure rate of appearance of oral glucose (RaO) using a dual glucose tracer method following standardized mixed meals taken after single sotagliflozin or canagliflozin doses.SETTING: Clinical research organization.DESIGN AND PARTICIPANTS: In a double-blind, 3-period crossover study (NCT01916863), 24 healthy partici", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31837264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 409, "text": "OBJECTIVE: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400 mg (n = 262", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29937430", "endSection": "abstract" }, { "offsetInBeginSection": 987, "offsetInEndSection": 1173, "text": "n, as well as by increasing GLP-1 secretion. Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 986, "text": "as the basis of this review. Clinical trials were identified using the Clinicaltrial.gov database.EXPERT OPINION: By a potential additional mechanism of action on intestinal glucose absorption linked to SGLT1 inhibition, sotagliflozin differentiates from SGLT2 inhibitors by reducing postprandial glucose excursion and insulin secreti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26548423", "endSection": "abstract" } ] }, { "body": "What is the main use of ETD fragmentation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34788003", "http://www.ncbi.nlm.nih.gov/pubmed/33068214", "http://www.ncbi.nlm.nih.gov/pubmed/31999103", "http://www.ncbi.nlm.nih.gov/pubmed/32070774" ], "ideal_answer": [ "Electron-based fragmentation methods have revolutionized biomolecular mass spectrometry, in particular native and top-down protein analysis." ], "exact_answer": [ "Analysis of intact proteins" ], "type": "factoid", "id": "6217d8f03a8413c653000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Electron transfer dissociation (ETD) is an analytically useful tool for primary structure interrogation of intact proteins, but its utility is limited by higher-order reactions with the products. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788003", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Electron-based fragmentation methods have revolutionized biomolecular mass spectrometry, in particular native and top-down protein analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31999103", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 686, "text": "nalyzed with less conventional mass spectrometry, i.e. using Electron Transfer Dissociation (ETD) for analyte fragmentation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32070774", "endSection": "abstract" }, { "offsetInBeginSection": 1599, "offsetInEndSection": 1774, "text": "Using a longer than normal electron transfer dissociation (ETD) reaction time, we obtained enhanced coverage of peptide bonds that facilitated the localization of O-glycosites", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33068214", "endSection": "abstract" } ] }, { "body": "What is the Bartter syndrome?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12920401", "http://www.ncbi.nlm.nih.gov/pubmed/30410160", "http://www.ncbi.nlm.nih.gov/pubmed/32335890", "http://www.ncbi.nlm.nih.gov/pubmed/9589375", "http://www.ncbi.nlm.nih.gov/pubmed/7771476", "http://www.ncbi.nlm.nih.gov/pubmed/31830341", "http://www.ncbi.nlm.nih.gov/pubmed/12589089", "http://www.ncbi.nlm.nih.gov/pubmed/1292416", "http://www.ncbi.nlm.nih.gov/pubmed/33509356", "http://www.ncbi.nlm.nih.gov/pubmed/20127383", "http://www.ncbi.nlm.nih.gov/pubmed/9203176", "http://www.ncbi.nlm.nih.gov/pubmed/11815871", "http://www.ncbi.nlm.nih.gov/pubmed/30756015", "http://www.ncbi.nlm.nih.gov/pubmed/26731830", "http://www.ncbi.nlm.nih.gov/pubmed/10617800", "http://www.ncbi.nlm.nih.gov/pubmed/24696311", "http://www.ncbi.nlm.nih.gov/pubmed/22470874", "http://www.ncbi.nlm.nih.gov/pubmed/27328514", "http://www.ncbi.nlm.nih.gov/pubmed/15518434", "http://www.ncbi.nlm.nih.gov/pubmed/16951440", "http://www.ncbi.nlm.nih.gov/pubmed/31820361", "http://www.ncbi.nlm.nih.gov/pubmed/28904439", "http://www.ncbi.nlm.nih.gov/pubmed/6945487", "http://www.ncbi.nlm.nih.gov/pubmed/22707176", "http://www.ncbi.nlm.nih.gov/pubmed/10419618", "http://www.ncbi.nlm.nih.gov/pubmed/28096565", "http://www.ncbi.nlm.nih.gov/pubmed/32296226", "http://www.ncbi.nlm.nih.gov/pubmed/32506108", "http://www.ncbi.nlm.nih.gov/pubmed/19915517", "http://www.ncbi.nlm.nih.gov/pubmed/15056980", "http://www.ncbi.nlm.nih.gov/pubmed/8966774", "http://www.ncbi.nlm.nih.gov/pubmed/26528764", "http://www.ncbi.nlm.nih.gov/pubmed/28327689", "http://www.ncbi.nlm.nih.gov/pubmed/32622651" ], "ideal_answer": [ "Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney. Its clinical features are renal salt wasting, hypokalemic metabolic alkalosis, elevated renin and aldosterone levels with normal or low blood pressure, polyuria, hypercalciuria and malnutrition.", "Bartter syndrome is a rare hereditary salt-losing tubulopathy caused by mutations of several genes in the thick ascending limb of Henle's loop, characterized by polyuria, hypokalemic metabolic alkalosis, growth retardation and normal blood pressure.", "Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney.", "Bartter syndrome is a syndrome associated with congenital tubular dysfunction, characterized by hypokalemia and metabolic alkalosis" ], "type": "summary", "id": "6060915b94d57fd879000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Bartter syndrome (BS) and Gitelman syndrome (GS) are syndromes associated with congenital tubular dysfunction, characterized by hypokalemia and metabolic alkalosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31830341", "endSection": "abstract" }, { "offsetInBeginSection": 166, "offsetInEndSection": 426, "text": "linically, BS is classified into two types: the severe antenatal/neonatal type, which develops during the fetal period with polyhydramnios and preterm delivery; and the relatively mild classic type, which is usually found during infancy with failure to thrive.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31830341", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 257, "text": "Bartter syndrome is a rare hereditary salt-losing tubulopathy caused by mutations of several genes in the thick ascending limb of Henle's loop, characterized by polyuria, hypokalemic metabolic alkalosis, growth retardation and normal blood pressure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31820361", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Bartter syndrome is an autosomal recessive disorder manifested by a defect in sodium-potassium-chloride transport in the thick ascending limb of Henle with different genetic origins and molecular pathophysiology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32506108", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 320, "text": "Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney. Its clinical features are renal salt wasting, hypokalemic metabolic alkalosis, elevated renin and aldosterone levels with normal or low blood pressure, polyuria, hypercalciuria and malnutrition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32296226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Bartter syndrome is a rare heterogeneous disease characterised by a deficiency in sodium and chloride absorption.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30756015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Bartter syndrome is an inherited renal tubular disorder with hypokalemia, hypochloremic metabolic alkalosis, normal blood pressure with hyper-reninemia and increased urinary loss of sodium, potassium and chloride.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16951440", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 354, "text": "Bartter's syndrome is characterised by constant simultaneous increase of plasma and urinary PGE2; this hypersecretion is insufficiently suppressed by indomethacin treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6945487", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Bartter syndrome is characterized by renal potassium and chloride loss, hypokalaemia, hypochloraemic metabolic alkalosis and increased plasma renin activity along with elevated angiotensin II and hyperaldosteronism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10419618", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Bartter's syndrome, a rare disorder affecting the renal tubular potassium handling, is characterized by metabolic alkalosis, hypokalemia and renal salt wasting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26731830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28904439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Bartter syndrome is an uncommon tubular disorder inherited as an autosomal recessive entity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15518434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Bartter syndrome is an inherited metabolic disorder characterized by hypokalemic alkalosis and high rennin-angiotensin-aldosteronism which can occur at all ages but mainly in childhood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32335890", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 446, "text": "Classical Bartter syndrome is caused by loss-of-function variants in the gene encoding basolateral chloride channel ClC-Kb (CLCNKB), which is a common type of Bartter syndrome characterized with diverse clinical manifestations ranging from severe to very mild.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32335890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Bartter syndrome is an autosomal recessive disorder caused by gene mutations that involve hypokalaemia, hypochloraemia and metabolic alkalosis along with raised serum renin, hyperaldosteronism and normal blood pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30410160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Bartter syndrome Type III is a rare autosomal recessive disorder resulting from an inherited defect in the thick ascending limb of the loop of henle of the nephrons in kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28327689", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 805, "text": "2) Antenatal Bartter syndrome with hypercalciuria and nephrocalcinosis or hyperprostaglandin E syndrome is a severe form, often revealed by hydramnios, prematurity and growth delay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10617800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "Bartter syndrome is a rare hereditary (autosomal recessive) salt-losing tubulopathy characterized by hypokalemia, hypochloremia, metabolic alkalosis, and normal blood pressure with hyperreninemia, The underlying renal abnormality results in excessive urinary losses of sodium, chloride, and potassium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22470874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "Among the different forms of hereditary renal tubulopathies associated with hypokalemia, metabolic alkalosis and normotension, two main types of disorders have been identified: Gitelman disease, which appears to be a homogeneous post-Henle's loop disorder, and Bartter syndrome, a heterogeneous Henle loop disorder. A specif", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9589375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Bartter syndrome is a rare hereditary (autosomal recessive) salt-losing tubulopathy characterized by hypokalemia, hypochloremia, metabolic alkalosis, and normal blood pressure with hyperreninemia, The underlying renal abnormality results in excessive urinary losses of sodium, chloride, and potassium. We report", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22470874", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "PURPOSE OF REVIEW: This review describes recent advances in our understanding of the genetic heterogeneity, pathophysiology and treatment of Bartter syndrome, a group of autosomal recessive disorders that are characterized by markedly reduced or absent salt transport by the thick ascendin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12920401", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 492, "text": "enatal Bartter syndrome, a subtype of Bartter-like syndrome, is characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Mutations i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12589089", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "ESTABLISHED FACTS: Bartter syndrome is a rare heterogeneous group of autosomal-recessive salt-losing renal tubular disorders that can present in fetal life (antenatal Bartter syndrome; ABS) as \"unexplained\" early-onset polyhydramnios, often associated with growth ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27328514", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "PURPOSE: Bartter syndrome is a rare hereditary salt-losing tubulopathy caused by mutations of several genes in the thick ascending limb of Henle's loop, characterized by polyuria, hypokalemic metabolic alkalosis, growth retardation and normal blood press", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31820361", "endSection": "abstract" }, { "offsetInBeginSection": 253, "offsetInEndSection": 462, "text": "In contrast to classic Bartter syndrome and Gitelman syndrome, the neonatal variant of Bartter syndrome has both the features of renal tubular hypokalemic alkalosis as well as profound systemic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9203176", "endSection": "abstract" }, { "offsetInBeginSection": 463, "offsetInEndSection": 627, "text": "Specifically, neonatal Bartter syndrome is characterized by intrauterine polyhydramnios, premature delivery, and life-threatening episodes of fever and dehydration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9203176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24696311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Bartter syndrome is a rare inherited defect in the thick ascending limb of the loop of Henle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28096565", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20127383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Bartter syndrome is an autosomic recessive disease characterized by severe polyuria and sodium renal loss.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19915517", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "BACKGROUND: Bartter syndrome is a rare autosomal recessive disorder characterized by hypokalemia, salt loss, and metaboli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22707176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Bartter syndromes are defined as a family of inherited recessive autosomal tubulopathies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10617800", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Bartter's Syndrome is a chronic electrolyte losing syndrome with symptoms and abnormalities that form an organized framework in which to study clinical effects of chronic electrolyte disturbances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1292416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Bartter's syndrome is a congenital abnormality characterized by metabolic alkalosis [corrected], hyperreninemic hyperaldosteronism, and hypokalemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7771476", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Bartter's syndrome: a chronic electrolyte losing syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1292416", "endSection": "title" }, { "offsetInBeginSection": 210, "offsetInEndSection": 379, "text": "Bartter syndrome results from a furosemide-like defect in sodium reabsorption in the Henle's loop leading to hypercalciuria and defect in urinary concentration capacity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32622651", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33509356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Bartter's syndrome (BS) is a disease with severe hypokalaemia due to renal potassium wasting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8966774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "OBJECTIVE: Bartter syndrome is a severe inherited tubulopathy characterized by postnatal salt wasting, severe polyuria, dehydration, failure to thrive and secondary hyperald", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26528764", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 694, "text": "Neonatal Bartter's syndrome is caused by mutations of NKCC2 or ROMK, classic Bartter's syndrome by mutations of ClC-Kb, Bartter's syndrome associated with sensorineural deafness is due to mutations of BSND, Gitelman's syndrome to mutations of NCCT and Bartter's syndrome associated with autosomal dominant hypocalcemia is linked to mutations of CASR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15056980", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Bartter syndrome, which presents clinically with polyuria, urinary potassium loss, hypokalemia, hypercalciuria, and alkalosis, is an autosomal recessive disorder with mutations in genes encoding the Na-K-2Cl cotransporter, the chloride channel CLC-NKB, and the potassium channel ROMK.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11815871", "endSection": "abstract" } ] }, { "body": "Can bergapten cause phototoxicity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34347307" ], "ideal_answer": [ "Yes, phototoxicity is a side effect of bergapten." ], "exact_answer": "yes", "type": "yesno", "id": "620588f9c9dfcb9c09000033", "snippets": [ { "offsetInBeginSection": 739, "offsetInEndSection": 841, "text": "Furthermore, the phototoxicity of bergapten combined with ultraviolet light has always been mentioned.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34347307", "endSection": "abstract" }, { "offsetInBeginSection": 1161, "offsetInEndSection": 1236, "text": "The phototoxicity of bergapten as a side effect should be further avoided. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34347307", "endSection": "abstract" } ] }, { "body": "Which syndromes are caused by LAMA1 mutations?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34423300", "http://www.ncbi.nlm.nih.gov/pubmed/34249907" ], "ideal_answer": [ "Poretti-Boltshauser and Joubert syndromes", "Poretti\u2013Boltshauser syndrome, Joubert syndrome" ], "exact_answer": [ [ "Poretti-Boltshauser syndrome" ], [ "Joubert syndrome" ] ], "type": "list", "id": "61f52fca882a024a10000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Identification of LAMA1 mutations ends diagnostic odyssey and has prognostic implications for patients with presumed Joubert syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34423300", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1376, "text": "Paediatric neurology syndromes are a broad and complex group of conditions with a large spectrum of clinical phenotypes. Joubert syndrome is a genetically heterogeneous neurological ciliopathy syndrome with molar tooth sign as the neuroimaging hallmark. We reviewed the clinical, radiological and genetic data for several families with a clinical diagnosis of Joubert syndrome but negative genetic analysis. We detected biallelic pathogenic variants in LAMA1, including novel alleles, in each of the four cases we report, thereby establishing a firm diagnosis of Poretti-Boltshauser syndrome. Analysis of brain MRI revealed cerebellar dysplasia and cerebellar cysts, associated with Poretti-Boltshauser syndrome and the absence of typical molar tooth signs. Using large UK patient cohorts, the relative prevalence of Joubert syndrome as a cause of intellectual disability was 0.2% and of Poretti-Boltshauser syndrome was 0.02%. We conclude that children with congenital brain disorders that mimic Joubert syndrome may have a delayed diagnosis due to poor recognition of key features on brain imaging and the lack of inclusion of LAMA1 on molecular genetic gene panels. We advocate the inclusion of LAMA1 genetic analysis on all intellectual disability and Joubert syndrome gene panels and promote a wider awareness of the clinical and radiological features of these syndromes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34423300", "endSection": "abstract" }, { "offsetInBeginSection": 897, "offsetInEndSection": 1227, "text": "Four COL18A1 mutants in three patients with scalp leisure in the occipital region; and five LAMA1 mutations in three patients with scalp leisure in the parietal region. Further assessments indicated that patients with COL18A1 mutations had Knobloch syndrome, and the patients with LAMA1 mutations had Poretti-Boltshauser syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34249907", "endSection": "abstract" } ] }, { "body": "What is the use of Lactin-V?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19543144", "http://www.ncbi.nlm.nih.gov/pubmed/20644497", "http://www.ncbi.nlm.nih.gov/pubmed/32402161", "http://www.ncbi.nlm.nih.gov/pubmed/21498386" ], "ideal_answer": [ "Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis and can be used for bacterial vaginosis. Lactin-V after treatment for cystitis was associated with a reduction in recurrent UTI." ], "type": "summary", "id": "602344ab1cb411341a00008e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32402161", "endSection": "title" }, { "offsetInBeginSection": 258, "offsetInEndSection": 462, "text": "METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of Lactobacillus crispatus CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32402161", "endSection": "abstract" }, { "offsetInBeginSection": 1928, "offsetInEndSection": 2111, "text": "CONCLUSIONS: The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32402161", "endSection": "abstract" }, { "offsetInBeginSection": 201, "offsetInEndSection": 390, "text": "We conducted a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V; Osel) for prevention of recurrent UTI in premenopausal women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498386", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1363, "text": "CONCLUSIONS: Lactin-V after treatment for cystitis is associated with a reduction in recurrent UTI. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498386", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 375, "text": "METHODS: A phase 2a study assessed colonization efficiency, safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by a vaginal applicator.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644497", "endSection": "abstract" }, { "offsetInBeginSection": 1491, "offsetInEndSection": 1581, "text": "CONCLUSIONS: LACTIN-V colonized well, and was safe and acceptable in women treated for BV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20644497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Phase 1 dose-ranging safety trial of Lactobacillus crispatus CTV-05 for the prevention of bacterial vaginosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19543144", "endSection": "title" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1368, "text": "SIONS: Lactin-V after treatment for cystitis is associated with a reduction in recurrent UTI. Large", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498386", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1267, "text": "-level vaginal colonization with L. crispatus (\u226510(6) 16S RNA gene copies per swab) throughout follow-up was associated with a significant reduction in recurrent UTI only for Lactin-V (RR for Lactin-V, .07; RR for placebo, 1.1; P < .01).CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498386", "endSection": "abstract" } ] }, { "body": "What is Congo red agar plates used for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30159221", "http://www.ncbi.nlm.nih.gov/pubmed/11774314", "http://www.ncbi.nlm.nih.gov/pubmed/23558135", "http://www.ncbi.nlm.nih.gov/pubmed/29621629", "http://www.ncbi.nlm.nih.gov/pubmed/30325222", "http://www.ncbi.nlm.nih.gov/pubmed/32982324", "http://www.ncbi.nlm.nih.gov/pubmed/14620986" ], "ideal_answer": [ "Congo red agar plates are used as a canonical indicator of biofilm-formation ability. Culture on Congo red agar plates in which slime-producing strains form black colonies, while nonslime-forming ones develop red colonies." ], "exact_answer": [ "Assessment of bacterial biofilm-formation ability." ], "type": "factoid", "id": "60329dc11cb411341a000147", "snippets": [ { "offsetInBeginSection": 1282, "offsetInEndSection": 1342, "text": "Biofilm-forming ability was tested on Congo Red agar plates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982324", "endSection": "abstract" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1289, "text": "The single MRSA isolate and 22 MSSA isolates were biofilm-producers on Congo red agar plates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29621629", "endSection": "abstract" }, { "offsetInBeginSection": 1534, "offsetInEndSection": 1646, "text": ", and rough morphotype on Congo red agar plates, indicating the formation of both curli fimbriae and cellulose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30325222", "endSection": "abstract" }, { "offsetInBeginSection": 345, "offsetInEndSection": 437, "text": "Biofilm formation was evaluated by microtiter plate, tube method and Congo red agar method. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30159221", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 906, "text": "a canonical indicator of biofilm-formation ability, on Congo red agar plates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23558135", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 621, "text": " by culture on Congo red agar plates in which slime-producing strains form black colonies, while nonslime-forming ones develop red colonies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14620986", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 619, "text": "Slime-forming ability was phenotypically tested on Congo red agar plates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11774314", "endSection": "abstract" } ] }, { "body": "What is the protein that is truncated to produce progerin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22895092", "http://www.ncbi.nlm.nih.gov/pubmed/20580717", "http://www.ncbi.nlm.nih.gov/pubmed/28229933", "http://www.ncbi.nlm.nih.gov/pubmed/30422822", "http://www.ncbi.nlm.nih.gov/pubmed/23213444", "http://www.ncbi.nlm.nih.gov/pubmed/21106101", "http://www.ncbi.nlm.nih.gov/pubmed/31280482", "http://www.ncbi.nlm.nih.gov/pubmed/21535442", "http://www.ncbi.nlm.nih.gov/pubmed/16129833", "http://www.ncbi.nlm.nih.gov/pubmed/22168243", "http://www.ncbi.nlm.nih.gov/pubmed/30257952", "http://www.ncbi.nlm.nih.gov/pubmed/31834988", "http://www.ncbi.nlm.nih.gov/pubmed/25510262", "http://www.ncbi.nlm.nih.gov/pubmed/32408587", "http://www.ncbi.nlm.nih.gov/pubmed/33139753", "http://www.ncbi.nlm.nih.gov/pubmed/22297442", "http://www.ncbi.nlm.nih.gov/pubmed/31833196", "http://www.ncbi.nlm.nih.gov/pubmed/16862216", "http://www.ncbi.nlm.nih.gov/pubmed/25652409", "http://www.ncbi.nlm.nih.gov/pubmed/32450911", "http://www.ncbi.nlm.nih.gov/pubmed/29702688", "http://www.ncbi.nlm.nih.gov/pubmed/27015553", "http://www.ncbi.nlm.nih.gov/pubmed/31714004", "http://www.ncbi.nlm.nih.gov/pubmed/24892300", "http://www.ncbi.nlm.nih.gov/pubmed/32048129", "http://www.ncbi.nlm.nih.gov/pubmed/24315443" ], "ideal_answer": [ "The truncated lamin A protein produced \"progerin", "Hutchinson Gilford progeria syndrome (HGPS) is a devastating accelerated aging disease caused by LMNA gene mutation. The truncated lamin A protein produced \"progerin\"" ], "exact_answer": [ "lamin-A", "prelamin", "lamin a", "progerin", "lamin A (LMNA)" ], "type": "factoid", "id": "601db4ac1cb411341a000048", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Mutations in lamin A (LMNA) are responsible for a variety of human dystrophic and metabolic diseases. Here, we created a mouse model in which progerin, the lamin A mutant protein that causes Hutchinson-Gilford progeria syndrome (HGPS), can be inducibly overexpressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31833196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare laminopathy that produces a mutant form of prelamin A, known as Progerin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31714004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Hutchinson Gilford progeria syndrome (HGPS) is a devastating accelerated aging disease caused by LMNA gene mutation. The truncated lamin A protein produced \"progerin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31834988", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 466, "text": "The main cause of HGPS is a sporadic autosomal dominant point mutation in LMNA gene resulting in differently spliced lamin A protein known as progerin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32048129", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 319, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder notably characterized by precocious and deadly atherosclerosis. Almost 90% of HGPS patients carry a LMNA p.G608G splice variant that leads to the expression of a permanently farnesylated abnormal form of prelamin-A, referred to as progerin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32408587", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 404, "text": " Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid disease characterized by the early onset of age-related phenotypes including arthritis, loss of body fat and hair, and atherosclerosis. Cells from affected individuals express a mutant version of the nuclear envelope protein lamin A (termed progerin) and have previously been shown to exhibit prominent histone modification changes.M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32450911", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 462, "text": "Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24315443", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 251, "text": "Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28229933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Hutchinson-Gilford progeria syndrome is a disorder of premature aging in children caused by de novo mutations in LMNA that lead to the synthesis of an internally truncated form of prelamin A (commonly called progerin). The production of progeri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30257952", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 258, "text": "It is caused by a mutation in LMNA leading to expression of truncated prelamin A (progerin) in the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30422822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Mutations in the lamin A/C (LMNA) gene that cause Hutchinson-Gilford progeria syndrome (HGPS) lead to expression of a protein called progerin with 50 amino acids deleted from the tail of prelamin A. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20580717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder, caused by mutation in the gene encoding lamin A/C, which produces a truncated protein called progerin. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33139753", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 326, "text": "rly 90% of HGPS sufferers carry a G608G mutation within exon 11 of LMNA, producing a truncated form of prelamin A, referred to as \"progerin\". Here", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23213444", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 391, "text": "s mutation results in the deletion of 50 amino acids at the carboxyl-terminal tail of prelamin A, and the truncated protein is called progerin. Pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25510262", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 398, "text": "wide. The premature aging disease Hutchinson-Gilford syndrome (HGPS) is also caused by defined mutations in the LMNA gene resulting in activation of a cryptic splice donor site leading to a defective truncated prelamin A protein called prog", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29702688", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 446, "text": "mutation results in the deletion of 50 amino acids at the carboxyl-terminal tail of prelamin A, producing a truncated farnesylated protein called progerin. Lami", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27015553", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 348, "text": "PS is almost always caused by a de novo point mutation in the lamin A gene (LMNA) that activates a cryptic splice donor site, producing a truncated mutant protein termed \"progerin.\" WT ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16129833", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "We sought to use splice-switching antisense oligonucleotides to produce a model of accelerated ageing by enhancing expression of progerin, translated from a mis-spliced lamin A gene (LMNA) transcript in human myogenic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24892300", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 597, "text": "HGPS arises from de novo mutations that activate a cryptic splice site in exon 11 of LMNA and result in progerin accumulation in tissues of mesodermal origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24892300", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1397, "text": "Oligonucleotides that annealed within the 150 base region of exon 11 that is missing in the progerin transcript, as well as those that targeted the normal exon 11 donor site induced the LMNA \u0394150 transcript, but most oligonucleotides also generated variable levels of LMNA transcript missing the entire exon 11.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24892300", "endSection": "abstract" }, { "offsetInBeginSection": 281, "offsetInEndSection": 441, "text": "This mutation results in the deletion of 50 amino acids at the carboxyl-terminal tail of prelamin A, producing a truncated farnesylated protein called progerin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27015553", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1015, "text": "This devastating incurable accelerated aging disease is caused by a silent mutation in the LMNA gene that generates a truncated lamin A protein \"progerin\" that exerts profound cellular toxicity and organismal decline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31280482", "endSection": "abstract" }, { "offsetInBeginSection": 97, "offsetInEndSection": 255, "text": "Accumulation of a truncated farnesylated prelamin A form, called progerin, is a hallmark of the severe premature ageing syndrome, Hutchinson-Gilford progeria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22297442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder, caused by mutation in the gene encoding lamin A/C, which produces a truncated protein called progerin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33139753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Mutations in the lamin A/C gene that cause Hutchinson-Gilford progeria syndrome lead to expression of a truncated, permanently farnesylated prelamin A variant called progerin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22895092", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 344, "text": "HGPS is almost always caused by a de novo point mutation in the lamin A gene (LMNA) that activates a cryptic splice donor site, producing a truncated mutant protein termed \"progerin.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16129833", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 434, "text": "We have proposed that miR-9-mediated regulation of prelamin A in the brain could explain the absence of primary neurological disease in Hutchinson-Gilford progeria syndrome, a genetic disease caused by the synthesis of an internally truncated form of farnesyl-prelamin A (progerin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25652409", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 773, "text": "In this disease the lamin A, a protein participating (with others lamins) in the formation of the nuclear lamina and implicated in nuclear stability, chromatin structure and gene expression, is present in a truncated version called progerin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21535442", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder because of a LMNA gene mutation that produces a mutant lamin A protein (progerin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22168243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 41, "text": " Progerin is a truncated form of lamin A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21106101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Hutchinson-Gilford progeria syndrome (HGPS) is caused by the production of a truncated prelamin A, called progerin, which is farnesylated at its carboxyl terminus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16862216", "endSection": "abstract" } ] }, { "body": "What are the effects of ibrutinib on CART cell production?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32683672", "http://www.ncbi.nlm.nih.gov/pubmed/32055000" ], "ideal_answer": [ "CART cell generation in the presence of ibrutinib resulted in increased cell viability and expansion of CLL patient-derived CART cells. Furthermore, ibrutinib enriched CART cells with less-differentiated na\u00efve-like phenotype and decreased expression of exhaustion markers including PD-1, TIM-3 and LAG-3. In addition, ibrutinib increased the cytokine release capacity of CLL patient-derived CART cells. In summary, BTK/ITK inhibition with ibrutinib during CART cell culture can improve yield and function of CLL patient-derived CART cell products." ], "type": "summary", "id": "62114bd93a8413c65300000d", "snippets": [ { "offsetInBeginSection": 1187, "offsetInEndSection": 1734, "text": "CART cell generation in the presence of ibrutinib resulted in increased cell viability and expansion of CLL patient-derived CART cells. Furthermore, ibrutinib enriched CART cells with less-differentiated na\u00efve-like phenotype and decreased expression of exhaustion markers including PD-1, TIM-3 and LAG-3. In addition, ibrutinib increased the cytokine release capacity of CLL patient-derived CART cells. In summary, BTK/ITK inhibition with ibrutinib during CART cell culture can improve yield and function of CLL patient-derived CART cell products.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32683672", "endSection": "abstract" } ] }, { "body": "What is the role of miR-193b in prostate cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20073067", "http://www.ncbi.nlm.nih.gov/pubmed/31225930" ], "ideal_answer": [ "Overexpression of miR-193b led to the inhibition of the majority of the 41 genes in prostate cancer cell lines.", "Overexpression of miR-193b in prostate cancer cell lines inhibited invasion and induced apoptosis. A majority of the top 150 genes downregulated when miR-193b was overexpressed in liposarcoma are overexpressed in metastatic prostate cancer and 41 miR-193b target genes overlapped with the 86 genes in the aggressive prostate cancer subtype 1 (PCS1) signature. Overexpression of miR-193b led to the inhibition of the majority of the 41 genes in prostate cancer cell lines. High expression of the 41 genes was correlated with recurrence of prostate cancer. Knockdown of miR-193b targets FOXM1 and RRM2 in prostate cancer cells phenocopied overexpression of miR-193b. Dual treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors decreased miR-193b promoter methylation and restored inhibition of FOXM1 and RRM2.", "Overexpression of miR-193b in prostate cancer cell lines inhibited invasion and induced apoptosis." ], "type": "summary", "id": "605794c294d57fd87900002d", "snippets": [ { "offsetInBeginSection": 637, "offsetInEndSection": 1732, "text": "Overexpression of miR-193b in prostate cancer cell lines inhibited invasion and induced apoptosis. We found that a majority of the top 150 genes downregulated when miR-193b was overexpressed in liposarcoma are overexpressed in metastatic prostate cancer and that 41 miR-193b target genes overlapped with the 86 genes in the aggressive prostate cancer subtype 1 (PCS1) signature. Overexpression of miR-193b led to the inhibition of the majority of the 41 genes in prostate cancer cell lines. High expression of the 41 genes was correlated with recurrence of prostate cancer. Knockdown of miR-193b targets FOXM1 and RRM2 in prostate cancer cells phenocopied overexpression of miR-193b. Dual treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors decreased miR-193b promoter methylation and restored inhibition of FOXM1 and RRM2. Our data suggest that silencing of miR-193b through promoter methylation may release the inhibition of PCS1 genes, contributing to prostate cancer progression and suggesting a possible therapeutic strategy for aggressive prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31225930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "miR-193b is an epigenetically regulated putative tumor suppressor in prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20073067", "endSection": "title" }, { "offsetInBeginSection": 1089, "offsetInEndSection": 1207, "text": "Altogether, our data suggest that miR-193b is an epigenetically silenced putative tumor suppressor in prostate cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20073067", "endSection": "abstract" } ] }, { "body": "What treatment was studied in the KEYNOTE-522 trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32396855", "http://www.ncbi.nlm.nih.gov/pubmed/34468351", "http://www.ncbi.nlm.nih.gov/pubmed/32709714", "http://www.ncbi.nlm.nih.gov/pubmed/32101663", "http://www.ncbi.nlm.nih.gov/pubmed/31420357", "http://www.ncbi.nlm.nih.gov/pubmed/32870473" ], "ideal_answer": [ "KEYNOTE-522 trial studied adjuvant pembrolizumab for patients with triple-negative breast cancer." ], "exact_answer": [ "pembrolizumab" ], "type": "factoid", "id": "602357ff1cb411341a00009a", "snippets": [ { "offsetInBeginSection": 138, "offsetInEndSection": 334, "text": "The phase 3 KEYNOTE-522 trial now shows that the addition of pembrolizumab to chemotherapy improves pathological complete response rates regardless of PD-L1 status and appears to improve survival.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32396855", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 1102, "text": "Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.METHODS: In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32101663", "endSection": "abstract" }, { "offsetInBeginSection": 2435, "offsetInEndSection": 2830, "text": "CONCLUSIONS: Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy. (Funded by Merck Sharp & Dohme [a subsidiary of Merck]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32101663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "PURPOSE: In both the IMpassion 130 trial in the metastatic setting and in Keynote 522 in the neoadjuvant setting, patients with triple-negative breast cancer (TNBC) showed benefit from PD-1 axis immunotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32709714", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1072, "text": "Additionally, in light of the results of the KEYNOTE-522 study of adjuvant pembrolizumab in TNBC, evaluation of immunotherapy in the early disease setting is a subject of great interest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32870473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 366, "text": "Pembrolizumab plus chemotherapy may be an effective neoadjuvant treatment for triple-negative breast cancer. In the phase III KEYNOTE-522 trial, patients treated with the PD-1 inhibitor in combination with chemotherapy prior to surgery were more likely to have a pathologic complete response than patients who received chemotherapy alone, regardless of PD-L1 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31420357", "endSection": "abstract" }, { "offsetInBeginSection": 885, "offsetInEndSection": 1071, "text": "Additionally, in light of the results of the KEYNOTE-522 study of adjuvant pembrolizumab in TNBC, evaluation of immunotherapy in the early disease setting is a subject of great interest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32870473", "endSection": "abstract" }, { "offsetInBeginSection": 898, "offsetInEndSection": 1085, "text": " in light of the results of the KEYNOTE-522 study of adjuvant pembrolizumab in TNBC, evaluation of immunotherapy in the early disease setting is a subject of great interest. This review a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32870473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "Pembrolizumab plus chemotherapy may be an effective neoadjuvant therapy in patients with early-stage triple-negative breast cancer: In an interim analysis of the phase III KEYNOTE-522 trial, patients treated with the combination had a higher pathologic complete response rate and trended toward better event-free survival than those who received chemotherapy alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34468351", "endSection": "abstract" } ] }, { "body": "Which disease is associated with DNAJB1-PRKACA fusion gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29751881", "http://www.ncbi.nlm.nih.gov/pubmed/32154962", "http://www.ncbi.nlm.nih.gov/pubmed/31736218", "http://www.ncbi.nlm.nih.gov/pubmed/29222914" ], "ideal_answer": [ "Fibrolamellar carcinoma is distinctive at clinical and histologic levels. A novel DNAJB1-PRKACA fusion gene characterizes almost all cases." ], "exact_answer": [ "Fibrolamellar carcinoma" ], "type": "factoid", "id": "6081b0b44e6a4cf630000009", "snippets": [ { "offsetInBeginSection": 1813, "offsetInEndSection": 1882, "text": "DNAJB1-PRKACA fusion gene found in sporadic fibrolamellar carcinomas,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29222914", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 379, "text": "the presence of a characteristic DNAJB1-PRKACA fusion gene has been associated with FLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31736218", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 194, "text": " The fibrolamellar carcinoma-associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and, thus, overexpression of Aurora kinase A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32154962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Fibrolamellar carcinoma is distinctive at clinical and histologic levels. A novel DNAJB1-PRKACA fusion gene characterizes almost all cases, distinguishes it from other hepatocellular neoplasms, and drives the pathogenesis of this unique tumor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29751881", "endSection": "abstract" } ] }, { "body": "What is NTI, Nerve Tissue Contrast Index", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31868248" ], "ideal_answer": [ "The Nerve Tissue Index NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a ultrasound image.", "The NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image.", "The NTI is a ratio between the brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image.", "The NTI is a ratio of average brightness levels of surrounding tissue and the median nerve used in the diagnostic of Carpal Tunnel Syndrome." ], "type": "summary", "id": "601eaaf61cb411341a000052", "snippets": [ { "offsetInBeginSection": 522, "offsetInEndSection": 1068, "text": "Carpal tunnel syndrome commonly results in loss of visualization of the nerve fascicular pattern on US images. To assess this phenomenon, we developed a nerve-tissue contrast index (NTI) method. The NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image. The area under the curve (AUC) from a receiver operating characteristic curve analysis and t test were used to assess the usefulness of the features for differentiation of patients with CTS from control participants", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868248", "endSection": "abstract" }, { "offsetInBeginSection": 719, "offsetInEndSection": 854, "text": "e NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868248", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 853, "text": "he NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31868248", "endSection": "abstract" } ] }, { "body": "When was dupilumab approved by EMA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31231591" ], "ideal_answer": [ "Dupilumab was approved fby the EMA in 2017." ], "exact_answer": [ "2017" ], "type": "factoid", "id": "606b75c194d57fd87900006c", "snippets": [ { "offsetInBeginSection": 380, "offsetInEndSection": 632, "text": "This article covers etiology of the disease and summarizes dermatologic treatment standards of selected countries binding prior to the registration of dupilumab by both the European Medicines Agency (EMA) and Federal Drug Administration (FDA) in 2017. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31231591", "endSection": "abstract" } ] }, { "body": "Describe bigPint", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32542031" ], "ideal_answer": [ "BigPint is a data visualization package available on Bioconductor under the GPL-3 license (https://bioconductor.org/packages/release/bioc/html/bigPint.html). This software introduces new visualization technology that enables independent layers of interactivity using Plotly in R, which aids in the exploration of large biological datasets. The bigPint package presents modernized versions of scatterplot matrices, volcano plots, and litre plots through the implementation of layered interactivity. These graphics have detected normalization issues, differential expression designation problems, and common analysis errors in public RNA-sequencing datasets. Researchers can apply bigPint graphics to their data by following recommended pipelines written in reproducible code in the user manual." ], "type": "summary", "id": "601ffd571cb411341a000079", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "bigPint: A Bioconductor visualization package that makes big data pint-sized.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32542031", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1319, "text": "Interactive data visualization is imperative in the biological sciences. The development of independent layers of interactivity has been in pursuit in the visualization community. We developed bigPint, a data visualization package available on Bioconductor under the GPL-3 license (https://bioconductor.org/packages/release/bioc/html/bigPint.html). Our software introduces new visualization technology that enables independent layers of interactivity using Plotly in R, which aids in the exploration of large biological datasets. The bigPint package presents modernized versions of scatterplot matrices, volcano plots, and litre plots through the implementation of layered interactivity. These graphics have detected normalization issues, differential expression designation problems, and common analysis errors in public RNA-sequencing datasets. Researchers can apply bigPint graphics to their data by following recommended pipelines written in reproducible code in the user manual. In this paper, we explain how we achieved the independent layers of interactivity that are behind bigPint graphics. Pseudocode and source code are provided. Computational scientists can leverage our open-source code to expand upon our layered interactive technology and/or apply it in new ways toward other computational biology tasks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32542031", "endSection": "abstract" } ] }, { "body": "Aducanumab can be used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34506904", "http://www.ncbi.nlm.nih.gov/pubmed/34827546", "http://www.ncbi.nlm.nih.gov/pubmed/34550687", "http://www.ncbi.nlm.nih.gov/pubmed/34263875", "http://www.ncbi.nlm.nih.gov/pubmed/34324167", "http://www.ncbi.nlm.nih.gov/pubmed/29686315", "http://www.ncbi.nlm.nih.gov/pubmed/34539340", "http://www.ncbi.nlm.nih.gov/pubmed/29181491", "http://www.ncbi.nlm.nih.gov/pubmed/34650610", "http://www.ncbi.nlm.nih.gov/pubmed/34535787", "http://www.ncbi.nlm.nih.gov/pubmed/33135381", "http://www.ncbi.nlm.nih.gov/pubmed/34585212", "http://www.ncbi.nlm.nih.gov/pubmed/34234067", "http://www.ncbi.nlm.nih.gov/pubmed/33836798", "http://www.ncbi.nlm.nih.gov/pubmed/34697913", "http://www.ncbi.nlm.nih.gov/pubmed/29067304", "http://www.ncbi.nlm.nih.gov/pubmed/34554383", "http://www.ncbi.nlm.nih.gov/pubmed/34366359", "http://www.ncbi.nlm.nih.gov/pubmed/34554982", "http://www.ncbi.nlm.nih.gov/pubmed/34741884", "http://www.ncbi.nlm.nih.gov/pubmed/27582220" ], "ideal_answer": [ "Aducanumab is approved for treatment of Alzheimer's disease." ], "exact_answer": [ "Alzheimer's disease" ], "type": "factoid", "id": "61f5914e882a024a1000000d", "snippets": [ { "offsetInBeginSection": 914, "offsetInEndSection": 1325, "text": "We highlight additional evidence consistent with the underwhelming efficacy of A\u03b2 oligomer-lowering agents, such as aducanumab, and of antioxidants, such as vitamin E, versus the so far isolated case report that DNase-I treatment for 2 months resulted in a severe AD patient's Mini-Mental State Exam score increasing from 3 to 18, reversing his diagnosis to moderate AD, according to the Mini-Mental State Exam.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34506904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "On 7 June 2021, aducanumab was granted accelerated approval for the treatment of Alzheimer disease (AD) by the FDA on the basis of amyloid-lowering effects considered reasonably likely to confer clinical benefit. This decision makes aducanumab the first new drug to be approved for the treatment of AD since 2003 and the first drug to ever be approved for modification of the course of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535787", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 983, "text": "While the vast majority of immunotherapies have been developed for A\u03b2 and tested in Alzheimer's disease, the field has progressed to targeting other proteins including \u03b1Syn. Despite showing some remarkable results in animal models, immunotherapies have largely failed final stages of clinical trials to date, with the exception of Aducanumab recently licenced in the US by the FDA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34539340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "The recent approval of aducanumab for Alzheimer's disease has heightened the interest in therapies targeting the amyloid hypothesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34550687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Aducanumab (Aduhelm), the first new drug to treat Alzheimer's disease since 2003, has received accelerated approval from the Food and Drug Administration (FDA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34554982", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 452, "text": "Aducanumab is approved in the United States for the treatment of mild cognitive impairment or mild-dementia stage of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34650610", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 582, "text": "On the one hand, aducanumab is the first drug to be approved for the treatment of the disease since 2003 and is the first drug to act on the alleged pathophysiological mechanisms of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34263875", "endSection": "abstract" }, { "offsetInBeginSection": 288, "offsetInEndSection": 393, "text": "In June 2021, aducanumab received its first approval in the USA for the treatment of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34324167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "On June 7, 2021, the US Food and Drug Administration (FDA) approved aducanumab, a monoclonal amyloid targeting \u03b2-amyloid, for the treatment for Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34263875", "endSection": "abstract" }, { "offsetInBeginSection": 403, "offsetInEndSection": 643, "text": "Aducanumab, a human monoclonal antibody that preferentially binds to aggregated amyloid-\u03b2 to reduce the number of amyloid plaques and slow disease progression, was approved to treat AD by the US Food and Drug Administration on June 7, 2021.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34234067", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 458, "text": "The regulatory approval of the disease-modifying agent aducanumab has brought more attention to the complexity of the diagnosis, evaluation, and treatment of AD and the difficult decisions payers and policy makers will face over the next few years as innovation continues in this space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34554383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Based on the reduction of amyloid \u03b2 plaques, US FDA has recently approved Aducanumab as a disease modifying treatment for Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34741884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Aducanumab is a human immunoglobulin G1 anti-amyloid beta (A\u03b2) antibody currently being evaluated for potential treatment of patients with early Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34697913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A Primer on the Evolution of Aducanumab: The First Antibody Approved for Treatment of Alzheimer's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34366359", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "The antibody aducanumab reduces A\u03b2 plaques in Alzheimer's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27582220", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Aducanumab, a human-derived antibody targeting amyloid-\u03b2 (A\u03b2), is in Phase 3 clinical trials for the treatment of Alzheimer's disease. Bi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29686315", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 402, "text": "2021, aducanumab received its first approval in the USA for the treatment of Alzheimer's disease. Accordin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34324167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Aducanumab, a human monoclonal antibody, was approved in June of 2021 as the first disease-modifying treatment for Alzheimer's disease by the United States Food and Drug Administration (U.S. FDA). A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34827546", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Aducanumab (Aduhelm), the first new drug to treat Alzheimer's disease since 2003, has received accelerated approval from the Food and Drug Administration (FDA).Thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34554982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Based on the reduction of amyloid \u03b2 plaques, US FDA has recently approved Aducanumab as a disease modifying treatment for Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34741884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "On June 7, 2021, the US Food and Drug Administration (FDA) approved aducanumab, a monoclonal amyloid targeting \u03b2-amyloid, for the treatment for Alzheimer's disease (AD). This ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34263875", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1136, "text": "This article summarizes the milestones in the development of aducanumab leading to this first approval for Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34324167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Aducanumab, a human-derived antibody targeting amyloid-\u03b2 (A\u03b2), is in Phase 3 clinical trials for the treatment of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29686315", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 376, "text": "INTRODUCTION: Aducanumab (BIIB037), a human monoclonal antibody selective for aggregated forms of amyloid beta, is being investigated as a disease-modifying treatment for Alzheimer's disease (AD).METHODS: This randomized, double-blind, placebo-controlled single ascending-dose study investigated the safety, tolerability, and pharmacokinetics (PK) of aducanumab in patients wi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29067304", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Clinical Development of Aducanumab, an Anti-A\u03b2 Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29181491", "endSection": "title" }, { "offsetInBeginSection": 961, "offsetInEndSection": 1041, "text": "These results justify further development of aducanumab for the treatment of AD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27582220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "BACKGROUND: Aducanumab is an anti-amyloid-\u03b2 (A\u03b2) antibody that achieved reduced amyloid pathology in Alzheimer's disease (AD) trials; however, it is controversial whether it also improved cognition, which has been suggested would require a sufficiently high cumulative dose of the antibody i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33836798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Aducanumab has been approved by the US Food and Drug Administration for treatment of Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "[Aducanumab and Alzheimer's disease: a critical reflection.]", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34263875", "endSection": "title" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1015, "text": "Aducanumab's efficacy as a treatment for the cognitive dysfunction in Alzheimer's disease cannot be proven by clinical trials with divergent outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33135381", "endSection": "abstract" } ] }, { "body": "Can IFNg induce the expression of IDO?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20811799", "http://www.ncbi.nlm.nih.gov/pubmed/30050535", "http://www.ncbi.nlm.nih.gov/pubmed/23613752", "http://www.ncbi.nlm.nih.gov/pubmed/22396896", "http://www.ncbi.nlm.nih.gov/pubmed/34819931" ], "ideal_answer": [ "Yes,\nIFNG-induce up-regulation of indoleamine 2,3-dioxygenase (IDO)" ], "exact_answer": "yes", "type": "yesno", "id": "6217d9bf3a8413c653000024", "snippets": [ { "offsetInBeginSection": 1604, "offsetInEndSection": 1649, "text": "IFNG inducible IDO/GTPCH inflammation cascade", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22396896", "endSection": "abstract" }, { "offsetInBeginSection": 826, "offsetInEndSection": 889, "text": "IFNG-induced up-regulation of indoleamine 2,3-dioxygenase (IDO)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20811799", "endSection": "abstract" }, { "offsetInBeginSection": 559, "offsetInEndSection": 606, "text": "IFN-\u03b3-induced indoleamine-2,3-dioxgenase (IDO) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23613752", "endSection": "abstract" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1520, "text": "strong and positive correlation between IDO1 and IFNG mRNA expression levels ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30050535", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1468, "text": " The tryptophan-degrading activity of IDO1 was not induced significantly by Chlamydia infection alone, but the addition of IFNG greatly increased its activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819931", "endSection": "abstract" } ] }, { "body": "Covid-19 is though to have arisen from what species?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32580969", "http://www.ncbi.nlm.nih.gov/pubmed/32369435", "http://www.ncbi.nlm.nih.gov/pubmed/34695342", "http://www.ncbi.nlm.nih.gov/pubmed/32760632", "http://www.ncbi.nlm.nih.gov/pubmed/34329631", "http://www.ncbi.nlm.nih.gov/pubmed/33457109" ], "ideal_answer": [ "COVID-19 caused by SARS-CoV-2 most likely originated in bats and transmitted to humans through a possible intermediate host." ], "exact_answer": [ "bats" ], "type": "factoid", "id": "601efe051cb411341a00006a", "snippets": [ { "offsetInBeginSection": 266, "offsetInEndSection": 391, "text": "COVID-19 caused by SARS-CoV-2 most likely originated in bats and transmitted to humans through a possible intermediate host. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32760632", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 569, "text": "cent Findings: Based on high similarities in the genome sequences, the virus is thought to have arisen from SARS-like CoVs in bats but the lack of an intermediate species containing a CoV with even greater similarity has so far eluded discovery. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33457109", "endSection": "abstract" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1069, "text": "es of the conclusions of the different documents here assessed show that even considering the zoonotic hypothesis as the most likely, with bats and pangolins being possibly in the origin of the coronavirus, today's date the intermediate source species of SARS-CoV-2 has not been confirmed yet. On the othe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34329631", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 357, "text": "Transmission rate of SARS-CoV-2 in the population is high, and the origin of this coronavirus appears to be related to some species of the bat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34695342", "endSection": "abstract" }, { "offsetInBeginSection": 585, "offsetInEndSection": 745, "text": "o other betacoronaviruses, SARS-CoV-2 appears to have crossed the species barrier, most likely from bats, clearly reinforcing the One Health concept. Veterinary", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32369435", "endSection": "abstract" } ] }, { "body": "Are TAMs good anticancer therapeutic targets?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29594035" ], "ideal_answer": [ "Therapeutic strategies to target TAMs to complement conventional therapies has yielded promising results." ], "exact_answer": "yes", "type": "yesno", "id": "602c2ade1cb411341a000124", "snippets": [ { "offsetInBeginSection": 924, "offsetInEndSection": 1162, "text": "Integrating therapeutic strategies to target TAMs to complement conventional therapies has yielded promising results in preclinical trials and warrants further investigation to determine its translational benefit in human cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29594035", "endSection": "abstract" } ] }, { "body": "Describe meCLICK-Seq", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33376781" ], "ideal_answer": [ "MeCLICK-Seq is a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. The method hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA.", "meCLICK-Seq (methylation CLICK-degradation Sequencing) is a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. The method hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA.", "The meCLICK-Seq (methylation CLICK-degradation Sequencing) is a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. It hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA." ], "type": "summary", "id": "620c2f4f3a8413c653000009", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "meCLICK-Seq, a Substrate-Hijacking and RNA Degradation Strategy for the Study of RNA Methylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33376781", "endSection": "title" }, { "offsetInBeginSection": 498, "offsetInEndSection": 992, "text": "Here we describe click-degraders, small molecules that can be covalently attached to RNA species through click-chemistry and can degrade them, that are akin to ribonucleases. By using these molecules, we have developed the meCLICK-Seq (methylation CLICK-degradation Sequencing) a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. The method hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33376781", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Lumasiran?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33789010", "http://www.ncbi.nlm.nih.gov/pubmed/32207686", "http://www.ncbi.nlm.nih.gov/pubmed/34022071", "http://www.ncbi.nlm.nih.gov/pubmed/33985991", "http://www.ncbi.nlm.nih.gov/pubmed/33852222", "http://www.ncbi.nlm.nih.gov/pubmed/33513899", "http://www.ncbi.nlm.nih.gov/pubmed/33405070" ], "ideal_answer": [ "Lumasiran is a subcutaneously administered small interfering RNA targeting the mRNA for hydroxyacid oxidase 1 gene that is used for the treatment of primary hyperoxaluria type 1 (PH1). By silencing the gene encoding glycolate oxidase, lumasiran depletes glycolate oxidase and thereby inhibits the synthesis of oxalate, which is the toxic metabolite that is directly associated with the clinical manifestations of PH1." ], "type": "summary", "id": "61f5bef2882a024a10000011", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "Lumasiran (Oxlumo\u2122) is a subcutaneously administered small interfering RNA (siRNA) targeting the mRNA for hydroxyacid oxidase 1 gene (HAO1; encodes glycolate oxidase) and was developed by Alnylam Pharmaceuticals for the treatment of primary hyperoxaluria type 1 (PH1). By silencing the gene encoding glycolate oxidase, lumasiran depletes glycolate oxidase and thereby inhibits the synthesis of oxalate, which is the toxic metabolite that is directly associated with the clinical manifestations of PH1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33405070", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1241, "text": " In this context we discuss nedosiran (Dicerna Pharmaceuticals, Inc.) and lumasiran (Alnylam Pharmaceuticals), which are both novel RNAi therapies for primary hyperoxaluria that selectively reduce hepatic expression of lactate dehydrogenase and glycolate oxidase respectively, reducing hepatic oxalate production and urinary oxalate levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34022071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "BACKGROUND AND OBJECTIVES: In the rare disease primary hyperoxaluria type 1, overproduction of oxalate by the liver causes kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing hepatic oxalate production.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33985991", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 403, "text": "There is an urgent need for drugs able to inhibit the liver production of oxalate and to prevent the disease progression; lumasiran, an innovative molecule based on RNAi interference, is one of the most promising drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33852222", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789010", "endSection": "title" }, { "offsetInBeginSection": 203, "offsetInEndSection": 342, "text": "Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789010", "endSection": "abstract" }, { "offsetInBeginSection": 197, "offsetInEndSection": 339, "text": "osis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxida", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Lumasiran (Oxlumo\u2122) is a subcutaneously administered small interfering RNA (siRNA) targeting the mRNA for hydroxyacid oxidase 1 gene (HAO1; encodes glycolate oxidase) and was developed by Alnylam Pharmaceuticals for the treatment of primary hyperoxaluria type 1 (PH1). By si", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33405070", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Lumasiran (Oxlumo\u2122) is a subcutaneously administered small interfering RNA (siRNA) targeting the mRNA for hydroxyacid oxidase 1 gene (HAO1; encodes glycolate oxidase) and was developed by Alnylam Pharmaceuticals for the treatment of primary hyperoxaluria type 1 (PH1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33405070", "endSection": "abstract" }, { "offsetInBeginSection": 269, "offsetInEndSection": 501, "text": "By silencing the gene encoding glycolate oxidase, lumasiran depletes glycolate oxidase and thereby inhibits the synthesis of oxalate, which is the toxic metabolite that is directly associated with the clinical manifestations of PH1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33405070", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 311, "text": "HAO1 (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32207686", "endSection": "abstract" }, { "offsetInBeginSection": 191, "offsetInEndSection": 574, "text": "c oxalosis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase.METHODS: In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with PH1 who were 6 years of age or older to receive subcutaneous lumasiran or placebo for 6 months (with doses given at baseline and at mo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789010", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 278, "text": "re, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33985991", "endSection": "abstract" }, { "offsetInBeginSection": 507, "offsetInEndSection": 712, "text": "Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33513899", "endSection": "abstract" } ] }, { "body": "Where are Goblet cells localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31751647", "http://www.ncbi.nlm.nih.gov/pubmed/31819932", "http://www.ncbi.nlm.nih.gov/pubmed/31734511", "http://www.ncbi.nlm.nih.gov/pubmed/31782555", "http://www.ncbi.nlm.nih.gov/pubmed/31762020", "http://www.ncbi.nlm.nih.gov/pubmed/31922915" ], "ideal_answer": [ "Goblet cells are found in the intestine, in the lungs, in the eyes etc. Goblet cells are localized in the epithelium." ], "exact_answer": [ "Epithelium" ], "type": "factoid", "id": "6049080c1cb411341a000164", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Goblet cells (GCs) and endocrine cells (ECs) play an important role in intestine physiology,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31782555", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Conjunctival goblet cells (CGCs) are specialized cells that produce and secrete soluble mucins to the tear film that bathes the ocular surface.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31734511", "endSection": "abstract" }, { "offsetInBeginSection": 1853, "offsetInEndSection": 1878, "text": "goblet cells in the lungs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31751647", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "The epithelial lining of the small intestine consists of multiple cell types, including Paneth cells and goblet cells, that work in cohort to maintain gut health. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31819932", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 73, "text": "goblet cell numbers are increased within the airway epithelium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31922915", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 438, "text": " The mucosa is lined with a stratified secretory epithelium rich in goblet cells that secrete neutral and acid mucins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31762020", "endSection": "abstract" } ] }, { "body": "What is OHRQoL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33625387", "http://www.ncbi.nlm.nih.gov/pubmed/33625386", "http://www.ncbi.nlm.nih.gov/pubmed/33042894", "http://www.ncbi.nlm.nih.gov/pubmed/32156276", "http://www.ncbi.nlm.nih.gov/pubmed/17333837", "http://www.ncbi.nlm.nih.gov/pubmed/33263952", "http://www.ncbi.nlm.nih.gov/pubmed/32196720", "http://www.ncbi.nlm.nih.gov/pubmed/27585185", "http://www.ncbi.nlm.nih.gov/pubmed/31753458", "http://www.ncbi.nlm.nih.gov/pubmed/33237227", "http://www.ncbi.nlm.nih.gov/pubmed/28019015", "http://www.ncbi.nlm.nih.gov/pubmed/32658317", "http://www.ncbi.nlm.nih.gov/pubmed/33626895", "http://www.ncbi.nlm.nih.gov/pubmed/28608821", "http://www.ncbi.nlm.nih.gov/pubmed/32757443", "http://www.ncbi.nlm.nih.gov/pubmed/20713456", "http://www.ncbi.nlm.nih.gov/pubmed/32372134", "http://www.ncbi.nlm.nih.gov/pubmed/17294288", "http://www.ncbi.nlm.nih.gov/pubmed/30148470", "http://www.ncbi.nlm.nih.gov/pubmed/29947814", "http://www.ncbi.nlm.nih.gov/pubmed/32593355", "http://www.ncbi.nlm.nih.gov/pubmed/24478972", "http://www.ncbi.nlm.nih.gov/pubmed/15239781", "http://www.ncbi.nlm.nih.gov/pubmed/21290909", "http://www.ncbi.nlm.nih.gov/pubmed/32715739", "http://www.ncbi.nlm.nih.gov/pubmed/22420792" ], "ideal_answer": [ "The assessment of the oral health-related quality of life (OHRQoL) is possible with the Oral Health Impact Profile-14 (OHIP-14) questionnaire comprising 7 subdomains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap", "Diseases and disorders that damage the mouth and face can disturb well-being and his self-esteem. Oral health-related quality of life (OHRQOL) is a relatively new but rapidly growing concept and can be assessed using a number of different methods including standardized questionnaires. The OHRQoL is a concept that includes functional, social, emotional, and environmental issues. How patients perceive their oral health-related quality of life (OHRQoL) is important for health-care provider for understanding and planning in patient management." ], "type": "summary", "id": "621e9e7b3a8413c653000054", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 65, "text": "To assess oral health-related quality of life (OHRQoL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33626895", "endSection": "abstract" }, { "offsetInBeginSection": 277, "offsetInEndSection": 486, "text": "oral health-related quality of life (OHRQoL) of an individual. Four main dimensions, oral function, oro-facial pain, oro-facial appearance and psychosocial impact, are suggested to cover the concept of OHRQoL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32196720", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 135, "text": "Several studies have shown that orthodontic anomalies may affect young people's Oral Health-Related Quality of Life (OHRQoL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32372134", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "This cross-sectional study compared the Oral-Health-Related Quality of Life (OHRQoL) in HIV negative patients (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32715739", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 209, "text": " To compare oral health-related quality of life (OHRQoL) and masticatory performance (MP) in patients treated with a mandibular complete denture (CD) and immediately loaded implant-supported prostheses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33625386", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 204, "text": "o evaluate the performance of complete dentures (CD) with anatomical and nonanatomical teeth in completely edentulous elderly individuals regarding oral health-related quality of life (OHRQoL), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33625387", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 422, "text": "How they perceive their oral health-related quality of life (OHRQoL) is important for health-care provider for understanding and planning in patient management.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33042894", "endSection": "abstract" }, { "offsetInBeginSection": 147, "offsetInEndSection": 456, "text": "The assessment of the oral health-related quality of life (OHRQoL) is possible with the Oral Health Impact Profile-14 (OHIP-14) questionnaire comprising 7 subdomains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33263952", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 338, "text": "The OHRQoL is a concept that surpasses an exclusively clinical perception and includes functional, social, emotional, and environmental issues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33237227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Oral health-related quality of life (OHRQoL) is a multidimensional construct that involves subjective evaluation of an individual's oral health.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28608821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "BACKGROUND: Oral health-related quality of life (OHRQoL) is a multidimensional, perception-based measure of how oral health affects social and physical functioning and self-image.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32593355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "STATEMENT OF PROBLEM: Oral health-related quality of life (OHRQoL) is a subjective measure that assesses a person's perception of oral health.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31753458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND: There is a lack of cohort studies on the influence factors of oral health-related quality of life (OHRQoL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32156276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Oral health-related quality of life (OHRQoL) is an important dental patient-reported outcome which is commonly based on 4 dimensions, namely Oral Function, Orofacial Pain, Orofacial Appearance and Psychosocial Impact. The Or", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32757443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "OBJECTIVES: Oral health-related quality of life (OHRQoL) is an important health indicator not only for individuals but also for oral health care providers to treat a person holis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28019015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Oral health-related quality of life (OHRQoL) is a multidimensional, perception-based measure of how oral health affects social and physical functioning and sel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32593355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Oral health-related quality of life (OHRQoL) is a multidimensional construct that measures well-being associated with the teeth, mouth, and face. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22420792", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Oral health-related quality of life (OHRQoL) is an important aspect of health outcomes and its assessment should be made using validated instruments. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20713456", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "Oral health-related quality of life (OHRQOL) is the perceived impact of one's own oral health on daily life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27585185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Oral health-related quality of life (OHRQOL) is the component of health-related quality of life that relates to the effects of oral diseases and dental interventions on patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32658317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "UNLABELLED: Oral Health-Related Quality of Life (OHRQOL) is the shift in the perception of health from merely the absence of disease and infirmity to complete physical, mental and social", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21290909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "BACKGROUND: Oral health-related quality of life (OHRQoL) is a multidimensional, perception-based measure of how oral health affects social and physical functioning and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32593355", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 190, "text": "Oral health-related quality of life (OHRQOL) is a relatively new but rapidly growing notion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24478972", "endSection": "abstract" }, { "offsetInBeginSection": 104, "offsetInEndSection": 196, "text": "Oral health-related quality of life (OHRQOL) is a relatively new but rapidly growing notion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17333837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "BACKGROUND: The Franciscan Hospital for Children Oral Health-Related Quality of Life questionnaire (FHC-OHRQOL-Q) is an instrument designed specifically for parents and caregivers of patients with special needs that has not yet been appli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30148470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Oral health-related quality of life (OHRQoL) is an important dental patient-reported outcome which is commonly based on 4 dimensions, namely Oral Function, Orofacial Pain, Orofacial Appearance and Psychosocial Impact.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32757443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Oral health-related quality of life (OHRQoL) is expected to be multidimensional.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17294288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "PURPOSE: Oral health-related quality of life (OHRQoL) is a\u00a0construct for assessing the self-perceived oral health of ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29947814", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "STATEMENT OF PROBLEM: Oral health-related quality of life (OHRQoL) is a subjective measure that assesses a person's perc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31753458", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "UNLABELLED: Oral health-related quality of life (OHRQOL) in edentulous patients with complete dentures is oft", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15239781", "endSection": "abstract" } ] }, { "body": "Which VKORC1 genotypes are associated with a need for lower warfarin maintenance dose?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31673144" ], "ideal_answer": [ "Patients with VKORC1-1639GA or AA required a lower warfarin maintenance dose." ], "exact_answer": [ [ "VKORC1-1639GA", "1639GA", "GA" ], [ "VKORC1-1639GA", "1639AA", "AA" ] ], "type": "list", "id": "606a296394d57fd87900004e", "snippets": [ { "offsetInBeginSection": 1049, "offsetInEndSection": 1220, "text": "Patients with VKORC1-1639GA or AA required a lower warfarin maintenance dose compared with patients with VKORC1-1639GG (SMD\u2009=\u2009-0.666, 95% CI: -0.887 to -0.445, I2\u2009=\u200933%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31673144", "endSection": "abstract" } ] }, { "body": "Which R/bioconductor have been developed for copy number analysis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24597965", "http://www.ncbi.nlm.nih.gov/pubmed/28088185", "http://www.ncbi.nlm.nih.gov/pubmed/22523482", "http://www.ncbi.nlm.nih.gov/pubmed/23442169", "http://www.ncbi.nlm.nih.gov/pubmed/24265680", "http://www.ncbi.nlm.nih.gov/pubmed/23419375", "http://www.ncbi.nlm.nih.gov/pubmed/31392308", "http://www.ncbi.nlm.nih.gov/pubmed/21070656" ], "ideal_answer": [ "CNVRanger, seqCNA, iGC, PLRS, SomatiCA, Copynumber, crlmm, KC-SMARTR are all R/bioconductor packages for copy number analysis" ], "exact_answer": [ [ "CNVRanger" ], [ "seqCNA" ], [ "iGC" ], [ "PLRS" ], [ "SomatiCA" ], [ "Copynumber" ], [ "crlmm" ], [ "KC-SMARTR" ] ], "type": "list", "id": "601ec0c91cb411341a00005f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "CNVRanger: association analysis of CNVs with gene expression and quantitative phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31392308", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 699, "text": "Copy number variation (CNV) is a major type of structural genomic variation that is increasingly studied across different species for association with diseases and production traits. Established protocols for experimental detection and computational inference of CNVs from SNP array and next-generation sequencing data are available. We present the CNVRanger R/Bioconductor package which implements a comprehensive toolbox for structured downstream analysis of CNVs. This includes functionality for summarizing individual CNV calls across a population, assessing overlap with functional genomic regions, and genome-wide association analysis with gene expression and quantitative phenotypes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31392308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "seqCNA: an R package for DNA copy number analysis in cancer using high-throughput sequencing.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24597965", "endSection": "title" }, { "offsetInBeginSection": 517, "offsetInEndSection": 1264, "text": "We introduce seqCNA, a parallelized R package for an integral copy number analysis of high-throughput sequencing cancer data. The package includes novel methodology on (i) filtering, reducing false positives, and (ii) GC content correction, improving copy number profile quality, especially under great read coverage and high correlation between GC content and copy number. Adequate analysis steps are automatically chosen based on availability of paired-end mapping, matched normal samples and genome annotation.CONCLUSIONS: seqCNA, available through Bioconductor, provides accurate copy number predictions in tumoural data, thanks to the extensive filtering and better GC bias correction, while providing an integrated and parallelized workflow.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24597965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "iGC-an integrated analysis package of gene expression and copy number alteration.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088185", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1510, "text": "With the advancement in high-throughput technologies, researchers can simultaneously investigate gene expression and copy number alteration (CNA) data from individual patients at a lower cost. Traditional analysis methods analyze each type of data individually and integrate their results using Venn diagrams. Challenges arise, however, when the results are irreproducible and inconsistent across multiple platforms. To address these issues, one possible approach is to concurrently analyze both gene expression profiling and CNAs in the same individual.RESULTS: We have developed an open-source R/Bioconductor package (iGC). Multiple input formats are supported and users can define their own criteria for identifying differentially expressed genes driven by CNAs. The analysis of two real microarray datasets demonstrated that the CNA-driven genes identified by the iGC package showed significantly higher Pearson correlation coefficients with their gene expression levels and copy numbers than those genes located in a genomic region with CNA. Compared with the Venn diagram approach, the iGC package showed better performance.CONCLUSION: The iGC package is effective and useful for identifying CNA-driven genes. By simultaneously considering both comparative genomic and transcriptomic data, it can provide better understanding of biological and medical questions. The iGC package's source code and manual are freely available at https://www.bioconductor.org/packages/release/bioc/html/iGC.html", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28088185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "PLRS: a flexible tool for the joint analysis of DNA copy number and mRNA expression data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419375", "endSection": "title" }, { "offsetInBeginSection": 8, "offsetInEndSection": 877, "text": " DNA copy number and mRNA expression are commonly used data types in cancer studies. Available software for integrative analysis arbitrarily fixes the parametric form of the association between the two molecular levels and hence offers no opportunities for modelling it. We present a new tool for flexible modelling of this association. PLRS uses a wide class of interpretable models including popular ones and incorporates prior biological knowledge. It is capable to identify the gene-specific type of relationship between gene copy number and mRNA expression. Moreover, it tests the strength of the association and provides confidence intervals. We illustrate PLRS using glioblastoma data from The Cancer Genome Atlas.AVAILABILITY AND IMPLEMENTATION: PLRS is implemented as an R package and available from Bioconductor (as of version 2.12; http://bioconductor.org). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23419375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "SomatiCA: identifying, characterizing and quantifying somatic copy number aberrations from cancer genome sequencing data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265680", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 952, "text": "Whole genome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. However, analysis of somatic copy-number changes from sequencing data is still challenging because of insufficient sequencing coverage, unknown tumor sample purity and subclonal heterogeneity. Here we describe a computational framework, named SomatiCA, which explicitly accounts for tumor purity and subclonality in the analysis of somatic copy-number profiles. Taking read depths (RD) and lesser allele frequencies (LAF) as input, SomatiCA will output 1) admixture rate for each tumor sample, 2) somatic allelic copy-number for each genomic segment, 3) fraction of tumor cells with subclonal change in each somatic copy number aberration (SCNA), and 4) a list of substantial genomic aberration events including gain, loss and LOH. SomatiCA is available as a Bioconductor R package at http://www.bioconductor.org/packages/2.13/bioc/html/SomatiCA.html.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24265680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Copynumber: Efficient algorithms for single- and multi-track copy number segmentation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23442169", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1218, "text": "Cancer progression is associated with genomic instability and an accumulation of gains and losses of DNA. The growing variety of tools for measuring genomic copy numbers, including various types of array-CGH, SNP arrays and high-throughput sequencing, calls for a coherent framework offering unified and consistent handling of single- and multi-track segmentation problems. In addition, there is a demand for highly computationally efficient segmentation algorithms, due to the emergence of very high density scans of copy number.RESULTS: A comprehensive Bioconductor package for copy number analysis is presented. The package offers a unified framework for single sample, multi-sample and multi-track segmentation and is based on statistically sound penalized least squares principles. Conditional on the number of breakpoints, the estimates are optimal in the least squares sense. A novel and computationally highly efficient algorithm is proposed that utilizes vector-based operations in R. Three case studies are presented.CONCLUSIONS: The R package copynumber is a software suite for segmentation of single- and multi-track copy number data using algorithms based on coherent least squares principles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23442169", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Using the R Package crlmm for Genotyping and Copy Number Estimation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22523482", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1028, "text": "Genotyping platforms such as Affymetrix can be used to assess genotype-phenotype as well as copy number-phenotype associations at millions of markers. While genotyping algorithms are largely concordant when assessed on HapMap samples, tools to assess copy number changes are more variable and often discordant. One explanation for the discordance is that copy number estimates are susceptible to systematic differences between groups of samples that were processed at different times or by different labs. Analysis algorithms that do not adjust for batch effects are prone to spurious measures of association. The R package crlmm implements a multilevel model that adjusts for batch effects and provides allele-specific estimates of copy number. This paper illustrates a workflow for the estimation of allele-specific copy number and integration of the marker-level estimates with complimentary Bioconductor software for inferring regions of copy number gain or loss. All analyses are performed in the statistical environment R.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22523482", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "KC-SMARTR: An R package for detection of statistically significant aberrations in multi-experiment aCGH data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070656", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 1877, "text": "Most approaches used to find recurrent or differential DNA Copy Number Alterations (CNA) in array Comparative Genomic Hybridization (aCGH) data from groups of tumour samples depend on the discretization of the aCGH data to gain, loss or no-change states. This causes loss of valuable biological information in tumour samples, which are frequently heterogeneous. We have previously developed an algorithm, KC-SMART, that bases its estimate of the magnitude of the CNA at a given genomic location on kernel convolution (Klijn et al., 2008). This accounts for the intensity of the probe signal, its local genomic environment and the signal distribution across multiple samples.RESULTS: Here we extend the approach to allow comparative analyses of two groups of samples and introduce the R implementation of these two approaches. The comparative module allows for a supervised analysis to be performed, to enable the identification of regions that are differentially aberrated between two user-defined classes.We analyzed data from a series of B- and T-cell lymphomas and were able to retrieve all positive control regions (VDJ regions) in addition to a number of new regions. A t-test employing segmented data, that we implemented, was also able to locate all the positive control regions and a number of new regions but these regions were highly fragmented.CONCLUSIONS: KC-SMARTR offers recurrent CNA and class specific CNA detection, at different genomic scales, in a single package without the need for additional segmentation. It is memory efficient and runs on a wide range of machines. Most importantly, it does not rely on data discretization and therefore maximally exploits the biological information in the aCGH data.The program is freely available from the Bioconductor website http://www.bioconductor.org/ under the terms of the GNU General Public License.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21070656", "endSection": "abstract" } ] }, { "body": "Is gabapentin effective for chronic pelvic pain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32979978", "http://www.ncbi.nlm.nih.gov/pubmed/34193515" ], "ideal_answer": [ "Based on data from multicentre, randomised, double-blind, placebo-controlled trial (GaPP2), treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo." ], "exact_answer": "no", "type": "yesno", "id": "6027434c1cb411341a0000dc", "snippets": [ { "offsetInBeginSection": 2014, "offsetInEndSection": 2759, "text": "There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13-16 weeks after randomisation. The mean worst NRS pain score was 7\u00b71 (standard deviation [SD] 2\u00b76) in the gabapentin group and 7\u00b74 (SD 2\u00b72) in the placebo group. Mean change from baseline was -1\u00b74 (SD 2\u00b73) in the gabapentin group and -1\u00b72 (SD 2\u00b71) in the placebo group (adjusted mean difference -0\u00b720 [97\u00b75% CI -0\u00b781 to 0\u00b742]; p=0\u00b747). The mean average NRS pain score was 4\u00b73 (SD 2\u00b73) in the gabapentin group and 4\u00b75 (SD 2\u00b72) in the placebo group. Mean change from baseline was -1\u00b71 (SD 2\u00b70) in the gabapentin group and -0\u00b79 (SD 1\u00b78) in the placebo group (adjusted mean difference -0\u00b718 [97\u00b75% CI -0\u00b771 to 0\u00b735]; p=0\u00b745).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32979978", "endSection": "abstract" }, { "offsetInBeginSection": 3036, "offsetInEndSection": 3540, "text": "INTERPRETATION: This study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32979978", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Gabapentin not effective for chronic pelvic pain in women.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34193515", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Gabapentin not effective for chronic pelvic pain in women", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34193515", "endSection": "title" } ] }, { "body": "Does the royal jelly contain proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33297150", "http://www.ncbi.nlm.nih.gov/pubmed/31936187", "http://www.ncbi.nlm.nih.gov/pubmed/32042077", "http://www.ncbi.nlm.nih.gov/pubmed/31473899" ], "ideal_answer": [ "Yes, main bioactive compounds of Royal Jelly, include proteins and peptides." ], "exact_answer": "yes", "type": "yesno", "id": "6056fbfc94d57fd87900001d", "snippets": [ { "offsetInBeginSection": 691, "offsetInEndSection": 997, "text": " We observed differences in the metabolome, proteome, and phytosterol compositions of royal jelly synthesized by nurse bees from multi-pesticide exposed colonies, including significant reductions of key nutrients such as 24-methylenecholesterol, major royal jelly proteins, and 10-hydroxy-2-decenoic acid. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33297150", "endSection": "abstract" }, { "offsetInBeginSection": 198, "offsetInEndSection": 285, "text": " Two-dimensional electrophoresis was used for the fractionation of royal jelly proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31473899", "endSection": "abstract" }, { "offsetInBeginSection": 828, "offsetInEndSection": 917, "text": "the main bioactive compounds of RJ, such as proteins, peptides, fatty acids, and phenolic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31936187", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 985, "text": " the expression of four of the major royal jelly proteins (MRJP1, MRJP2, MRJP4, and MRJP5) and also several proteins associated with carbohydrate metabolism and energy synthesis, the antioxidant system, detoxification, biosynthesis, amino acid metabolism, transcription and translation, protein folding and binding, olfaction, and learning and memory.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32042077", "endSection": "abstract" } ] }, { "body": "What is the brand name for erenumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32049005", "http://www.ncbi.nlm.nih.gov/pubmed/32753854", "http://www.ncbi.nlm.nih.gov/pubmed/32259079", "http://www.ncbi.nlm.nih.gov/pubmed/29968151" ], "ideal_answer": [ "Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine.", "Erenumab-aooe (erenumab, Aimovig\u00ae)-a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor-is approved for the prevention of migraine in adults in a number of countries" ], "exact_answer": [ "Aimovig" ], "type": "factoid", "id": "601dbe101cb411341a00004c", "snippets": [ { "offsetInBeginSection": 85, "offsetInEndSection": 297, "text": "Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32049005", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 221, "text": " Erenumab-aooe (erenumab, Aimovig\u00ae)-a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor-is approved for the prevention of migraine in adults in a number of countries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Purpose: Erenumab-aooe (erenumab, Aimovig\u00ae)-a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor-is approved for the prevention of migraine in adults in a number of cou", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Amgen and Novartis are developing erenumab (AIMOVIG\u2122, erenumab-aooe)-a fully human monoclonal antibody calcitonin gene-related peptide (CGRP) receptor antagonist-for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29968151", "endSection": "abstract" }, { "offsetInBeginSection": 85, "offsetInEndSection": 298, "text": "Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32049005", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Discovery of the Migraine Prevention Therapeutic Aimovig (Erenumab), the First FDA-Approved Antibody against a G-Protein-Coupled Receptor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32259079", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "In 2018, the United States Food and Drug Administration (FDA) approved Aimovig (erenumab) for the prevention of migraine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32259079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Purpose: Erenumab-aooe (erenumab, Aimovig\u00ae)-a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor-is approved for the prevention of migraine in adults in a number of c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32753854", "endSection": "abstract" } ] }, { "body": "Which protein does capmatinib bind?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32557339" ], "ideal_answer": [ "Capmatinib binds MET." ], "exact_answer": [ "MET", "mesenchymal-epithelial transition" ], "type": "factoid", "id": "606b7d6c94d57fd87900006f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 644, "text": "Capmatinib (Tabrecta\u2122) is an oral, small molecule mesenchymal-epithelial transition (MET) inhibitor being developed by Novartis Oncology, under a license from Incyte Corporation, for the treatment of lung cancer. Capmatinib targets and selectively binds to MET, including the mutant variant produced by exon 14 skipping, and inhibits cancer cell growth driven by the mutant MET variant. In May 2020, oral capmatinib received its first global approval in the USA for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have a mutation that leads to MET exon 14 skipping, as detected by an FDA-approved test. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32557339", "endSection": "abstract" } ] }, { "body": "Which neuropsychiatric disorders are associated with 16p13.11 genomic copy number variants?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22523559" ], "ideal_answer": [ "schizophrenia, autism, mental retardation, ADHD, epilepsy", "16p13.11 genomic copy number variants are implicated in several neuropsychiatric disorders, such as schizophrenia, autism, mental retardation, ADHD and epilepsy.", "schizophrenia, autism, mental retardation, ADHD and epilepsy" ], "exact_answer": [ [ "schizophrenia" ], [ "autism" ], [ "mental retardation" ], [ "ADHD" ], [ "epilepsy" ] ], "type": "list", "id": "60281b1c1cb411341a0000f3", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "16p13.11 genomic copy number variants are implicated in several neuropsychiatric disorders, such as schizophrenia, autism, mental retardation, ADHD and epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22523559", "endSection": "abstract" } ] }, { "body": "What is carcinoma en cuirasse?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29197843", "http://www.ncbi.nlm.nih.gov/pubmed/24852775", "http://www.ncbi.nlm.nih.gov/pubmed/24068134", "http://www.ncbi.nlm.nih.gov/pubmed/14756657", "http://www.ncbi.nlm.nih.gov/pubmed/34745972", "http://www.ncbi.nlm.nih.gov/pubmed/33252056", "http://www.ncbi.nlm.nih.gov/pubmed/12377111", "http://www.ncbi.nlm.nih.gov/pubmed/2477873", "http://www.ncbi.nlm.nih.gov/pubmed/20551556", "http://www.ncbi.nlm.nih.gov/pubmed/31191149", "http://www.ncbi.nlm.nih.gov/pubmed/32190027", "http://www.ncbi.nlm.nih.gov/pubmed/25395467", "http://www.ncbi.nlm.nih.gov/pubmed/31040139" ], "ideal_answer": [ "Breast carcinoma en cuirasse is an extremely rare form of cutaneous metastases of breast cancer, characterized by diffuse sclerodermoid induration of the skin." ], "type": "summary", "id": "61f575f7882a024a10000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Breast carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastases of breast cancer, characterized by diffuse sclerodermoid induration of the skin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34745972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Breast carcinoma en cuirasse is a very rare form of cutaneous metastases of breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33252056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastasis of breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31191149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "We present a case of carcinoma en cuirasse as a presentation of advanced lobular breast carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29197843", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 389, "text": "The primary malignant tumor that most commonly metastasizes to the skin in women is breast cancer, which can be manifested through papulonodular lesions, erysipeloid or sclerodermiform infiltration, en cuirasse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24068134", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 199, "text": "Carcinoma en cuirasse is an unusual form of metastatic cutaneous carcinoma, almost exclusively described as deposits secondary to breast carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25395467", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 516, "text": "Breast dermal metastases are classified into eight clinicohistopathologic groups, one of which is carcinoma en cuirasse.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32190027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND: Carcinoma en cuirasse is a form of metastatic cutaneous breast malignancy occurring most commonly on the chest as a recurrence of breast cancer, but it can be the primary presentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14756657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "BACKGROUND: Carcinoma en cuirasse is a form of metastatic cutaneous breast malignancy occurring most commonly on the chest as a recurrence of breast cancer, but it can be the primary p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14756657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Breast carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastases of breast cancer, characterized by diffuse sclerodermoid induration of the skin. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34745972", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 477, "text": "tases of the skin most frequently occur in breast cancer, and manifest as carcinoma en cuirasse characterized by thoracic wall lesions in the form of erythematous foci with induration as in scleroderma, or as exulcerating nodules scattered all over the skin surface. We st", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12377111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Breast carcinoma en cuirasse is a very rare form of cutaneous metastases of breast cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33252056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Carcinoma en cuirasse is a form of cutaneous metastasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20551556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastasis of breast cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31191149", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 458, "text": "BACKGROUND: Carcinoma en cuirasse is a form of metastatic cutaneous breast malignancy occurring most commonly on the chest as a recurrence of breast cancer, but it can be the primary presentation.OBJECTIVE: To discuss the clinical features of carcinoma en cuirasse that distinguish it from hypertrophic scars and keloids of the chest.METHOD: We report a 63-year-old woman with primary cutaneous breast carcinoma presenting as keloid nodules on the chest that", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14756657", "endSection": "abstract" }, { "offsetInBeginSection": 539, "offsetInEndSection": 832, "text": " and genital ulceration. A cutaneous biopsy with subsequent immunohistochemical staining showed lymphatic dissemination of adenocarcinoma to the vulva.DISCUSSION: Carcinoma \"en cuirasse\" is a rare presentation of cutaneous metastasis in which the affected skin shows hardening and induration, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24852775", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Carcinoma en cuirasse of the breast, which invades the skin via lymphatics and may encase the entire thorax and abdomen, is poorly controlled by surgery, chemotherapy, or conventional irradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2477873", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Breast carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastases of breast cancer, characterized by diffuse sclerodermoid induration of the skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34745972", "endSection": "abstract" } ] }, { "body": "What is carboxyglutamate?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31040920", "http://www.ncbi.nlm.nih.gov/pubmed/33037248", "http://www.ncbi.nlm.nih.gov/pubmed/29856932" ], "ideal_answer": [ "One of the important glutamic acid modifications is post-translationally modified 4-carboxyglutamate." ], "exact_answer": [ "carboxyglutamateis a a post-translational glutamic acidof" ], "type": "factoid", "id": "6082f0ec4e6a4cf63000000e", "snippets": [ { "offsetInBeginSection": 87, "offsetInEndSection": 189, "text": " One of the important glutamic acid modifications is post-translationally modified 4-carboxyglutamate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33037248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Vitamin K serves as an essential co-factor in the \u03b3-carboxylation of glutamate to \u03b3-carboxyglutamate (GLA), a post-translational modification mediated by gamma-glutamyl carboxylase (GGCX) and vitamin K oxidoreductases (VKORC1 or VKORC1L1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31040920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Vitamin K (VK) is an essential cofactor for the post-translational conversion of peptide-bound glutamate to \u03b3-carboxyglutamate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29856932", "endSection": "abstract" } ] }, { "body": "What is Morton's Neuroma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24960551", "http://www.ncbi.nlm.nih.gov/pubmed/26963851", "http://www.ncbi.nlm.nih.gov/pubmed/22811757", "http://www.ncbi.nlm.nih.gov/pubmed/26815264", "http://www.ncbi.nlm.nih.gov/pubmed/32674597", "http://www.ncbi.nlm.nih.gov/pubmed/20882801", "http://www.ncbi.nlm.nih.gov/pubmed/32013586", "http://www.ncbi.nlm.nih.gov/pubmed/33012024", "http://www.ncbi.nlm.nih.gov/pubmed/32701133", "http://www.ncbi.nlm.nih.gov/pubmed/32555077", "http://www.ncbi.nlm.nih.gov/pubmed/34258038", "http://www.ncbi.nlm.nih.gov/pubmed/20086908", "http://www.ncbi.nlm.nih.gov/pubmed/14677525", "http://www.ncbi.nlm.nih.gov/pubmed/31718949", "http://www.ncbi.nlm.nih.gov/pubmed/28030965", "http://www.ncbi.nlm.nih.gov/pubmed/2794625", "http://www.ncbi.nlm.nih.gov/pubmed/33179062", "http://www.ncbi.nlm.nih.gov/pubmed/33168237", "http://www.ncbi.nlm.nih.gov/pubmed/31177965", "http://www.ncbi.nlm.nih.gov/pubmed/22694086", "http://www.ncbi.nlm.nih.gov/pubmed/1919367", "http://www.ncbi.nlm.nih.gov/pubmed/15266472" ], "ideal_answer": [ "Morton's neuroma (MN) is a neuralgia involving the common plantar digital nerves of the metatarsal region.", "Morton's neuromas are abnormalities of the common digital nerve branch located between the lesser metatarsal heads and is a common cause of foot pain." ], "type": "summary", "id": "601ef7cf1cb411341a000068", "snippets": [ { "offsetInBeginSection": 84, "offsetInEndSection": 208, "text": "Morton's neuroma (MN) is an entrapment degenerative neuropathy with a strong predilection for the 3rd interdigital web space", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31718949", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 118, "text": "Morton's neuroma (MN) is a neuralgia involving the common plantar digital nerves of the metatarsal region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31177965", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 63, "text": "Morton's neuroma is a common cause of forefoot pain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32013586", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 67, "text": "Morton's neuroma is a frequent cause of metatarsalgia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32674597", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 128, "text": "Morton's neuromas are abnormalities of the common digital nerve branch located between the lesser metatarsal heads. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32701133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Morton's neuroma is regarded as a type of entrapment neuropathy, therefore, neurolysis as surgical treatment is preferable to neurectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2794625", "endSection": "abstract" }, { "offsetInBeginSection": 691, "offsetInEndSection": 837, "text": "Since Morton's neuroma is considered to be a type of entrapment neuropathy, it is reasonable to think that neurolysis is preferable to neurectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2794625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Morton's neuroma is a painful lesion of the interdigital nerve, usually at the third intermetatarsal space, associated with fibrotic changes in the nerve, microvascular degeneration, and deregulation of sympathetic innervation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34258038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Morton's neuroma is the fibrous enlargement of the interdigital nerve branches, usually in the second and third interspace between the metatarsal heads where the lateral and medial plantar nerves often join.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26815264", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Morton's \"neuroma\" is a perineurofibrosis of an interdigital nerve.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1919367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Morton's neuroma is a frequent cause of pain in the forefoot that commonly occurs in the third intermetatarsal space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14677525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Morton's neuroma is a painful lesion of the interdigital nerve, usually at the third intermetatarsal space, associated with fibrotic changes in the nerve, microvascular degeneration, and deregulation of sympathetic innervation. Patien", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34258038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "BACKGROUND: Morton's neuroma is a common cause of pain that radiates from between the third and fourth metatarsals and which, when symptomatic, creates sensations of burning or sharp pain and numbness on the fo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22811757", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26963851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Civinini Morton's Syndrome (CMS), better known as Morton's Neuroma, is a benign enlargement that typically affects the third common digital branch of the plantar nerve. It is", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32555077", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "BACKGROUND: Interdigital neuroma (IN), otherwise known as Morton's neuroma, is a common cause of metatarsalgia presenting to the elective foot and ankle c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28030965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Abstract BACKGROUND:Morton's neuroma is a frequently painful condition of the forefoot, causing sufferers to seek medical care to alleviate symptoms. A ple", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24960551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "INTRODUCTION: Morton's neuroma is an entrapment neuropathy of the third common plantar digital nerve, caused by the deep transverse metatarsal li", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33012024", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "BACKGROUND: Morton's neuroma is a common, paroxysmal neuralgia affecting the web spaces of the toes, typicall", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15266472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Morton's neuroma is a commonly encountered cause of forefoot pain, which may limit weight-bearing activities and footwear choices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33168237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26963851", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Morton's neuroma, known also as intermetatarsal or interdigital neuroma, is a common foot injury that often curtails athletic activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20086908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "BACKGROUND: Morton's neuromas are abnormalities of the common digital nerve branch located between the lesser metat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33179062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Morton's neuroma is an entrapment neuropathy of the plantar digital nerve.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22694086", "endSection": "abstract" } ] }, { "body": "Which company produces the HercepTest?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30668632" ], "ideal_answer": [ "DAKO is the company producing the companion diagnostic HercepTest." ], "exact_answer": [ "DAKO" ], "type": "factoid", "id": "606bff2194d57fd879000075", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The FDA-Approved Breast Cancer HER2 Evaluation Kit (HercepTest; Dako) May Miss Some HER2-Positive Breast Cancers.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30668632", "endSection": "title" } ] }, { "body": "Does UBE4B promote renal cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32021266" ], "ideal_answer": [ "Yes. UBE4B might act as an oncogene in regulating renal cancer development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of renal cancer patients." ], "exact_answer": "yes", "type": "yesno", "id": "6217c0b63a8413c65300001e", "snippets": [ { "offsetInBeginSection": 1638, "offsetInEndSection": 1832, "text": "UBE4B might act as an oncogene in regulating RCC development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of RCC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32021266", "endSection": "abstract" } ] }, { "body": "Does addition of valproic acid improve survival of patients with diffuse intrinsic pontine glioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24293221", "http://www.ncbi.nlm.nih.gov/pubmed/32285998" ], "ideal_answer": [ "No. Addition of valproic acid and bevacizumab to radiation was well tolerated but did not appear to improve survival in children with diffuse intrinsic pontine glioma." ], "exact_answer": "no", "type": "yesno", "id": "6025d9e41cb411341a0000b7", "snippets": [ { "offsetInBeginSection": 1151, "offsetInEndSection": 1434, "text": "Median event-free survival (EFS) and overall survival (OS) for DIPG were 7.8 (95% CI 5.6-8.2) and 10.3 (7.4-13.4) months, and estimated one-year EFS was 12% (2%-31%). Median EFS and OS for HGG were 9.1 (6.4-11) and 12.1 (10-22.1) months, and estimated one-year EFS was 24% (7%-45%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32285998", "endSection": "abstract" }, { "offsetInBeginSection": 1548, "offsetInEndSection": 1693, "text": "CONCLUSION: Addition of VPA and bevacizumab to radiation was well tolerated but did not appear to improve EFS or OS in children with DIPG or HGG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32285998", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 981, "text": "Event-free survival and overall survival of patients not treated with valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a parametric multivariate regression test for time-to-failure data) showed a statistically significant superiority of the median event-free survival of treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33-0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24293221", "endSection": "abstract" } ] }, { "body": "List the main protein families found in human tears?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31369467", "http://www.ncbi.nlm.nih.gov/pubmed/31951085", "http://www.ncbi.nlm.nih.gov/pubmed/34489718", "http://www.ncbi.nlm.nih.gov/pubmed/34012227" ], "ideal_answer": [ "Lipocalin\nCystatin S (CST4), \ncalcyclin (S100A6),\ncalgranulin A (S100A8) \nmatrix metalloproteinase 9 (MMP9)\nLTF, \nLYZ, \nZAG,\nDNAJC3" ], "exact_answer": [ [ "Lipocalin" ], [ "Cystatin S" ], [ "calcyclin" ], [ "calgranulin A" ], [ "matrix metalloproteinase 9" ], [ "LTF" ], [ "LYZ" ], [ "ZAG" ], [ "DNAJC3" ] ], "type": "list", "id": "6217dccc3a8413c65300002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 35, "text": "Tear lipocalin is a primate protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34489718", "endSection": "abstract" }, { "offsetInBeginSection": 32, "offsetInEndSection": 155, "text": " tear concentration of cystatin S (CST4), calcyclin (S100A6), calgranulin A (S100A8), and matrix metalloproteinase 9 (MMP9)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34012227", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1309, "text": "LTF, LYZ, ZAG, and DNAJC3 have the potential to be the biomarkers of DE in diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31951085", "endSection": "abstract" } ] }, { "body": "In what year did Gregor Mendel die?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/1887835", "http://www.ncbi.nlm.nih.gov/pubmed/14602707" ], "ideal_answer": [ "The life and personality of Johann Gregor Mendel (1822-1884)", "Gregor Mendel, OSA (1822-1884), founder of scientific genetics.", "Johann Gregor Mendel 1822-1884" ], "exact_answer": [ "1884" ], "type": "factoid", "id": "601ff4021cb411341a000075", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 49, "text": "Historical study: Johann Gregor Mendel 1822-1884.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1887835", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "The life and personality of Johann Gregor Mendel (1822-1884)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1887835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Gregor Mendel, OSA (1822-1884), founder of scientific genetics.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14602707", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "The life and personality of Johann Gregor Mendel (1822-1884), the founder of scientific genetics, are reviewed against the contemporary background of his times.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1887835", "endSection": "abstract" } ] }, { "body": "List 4 monoclonal antibodies in development for the prevention of migraine.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28644160" ], "ideal_answer": [ "Four monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab)" ], "exact_answer": [ [ "ALD403", "eptinezumab" ], [ "AMG334", "erenumab" ], [ "LY2951742", "galcanezumab" ], [ "TEV-48125", "fremanezumab" ] ], "type": "list", "id": "6026dc481cb411341a0000d0", "snippets": [ { "offsetInBeginSection": 279, "offsetInEndSection": 500, "text": "Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28644160", "endSection": "abstract" } ] }, { "body": "Is there a role for CADM1 in Myelodysplastic syndrome (MDS)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34638130" ], "ideal_answer": [ "Yes, CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies with deletion of the long arm of chromosome 11.", "Yes. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.", "Yes. Together with the frequent simultaneous deletions of KMT2A, ATM and CBL and mutations of ASXL1, SF3B1 and CBL, CADM1 may be important in the physiopathology of the del(11q) MDS." ], "exact_answer": "no", "type": "yesno", "id": "6212c25c3a8413c653000019", "snippets": [ { "offsetInBeginSection": 1355, "offsetInEndSection": 1638, "text": "Together with the frequent simultaneous deletions of KMT2A, ATM and CBL and mutations of ASXL1, SF3B1 and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34638130", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34638130", "endSection": "title" } ] }, { "body": "Which drugs are in the Segluromet combination pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30938372", "http://www.ncbi.nlm.nih.gov/pubmed/29476348", "http://www.ncbi.nlm.nih.gov/pubmed/30724637" ], "ideal_answer": [ "Segluromet includes combinations of ertugliflozin and metformin. It has recently been approved by the US FDA as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM." ], "exact_answer": [ [ "ertugliflozin" ], [ "metformin" ] ], "type": "list", "id": "61fbc51ec9dfcb9c0900000f", "snippets": [ { "offsetInBeginSection": 175, "offsetInEndSection": 606, "text": "Ertugliflozin, a highly selective and reversible SGLT2 inhibitor, is the latest addition to the gliflozin class of SGLT2 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). It was granted approval by the U.S. Food and Drug Administration (FDA) in December 2017 for treatment of T2DM as a monotherapy, and as part of two separate fixed-dose combination therapies with sitagliptin (Steglujan) and metformin (Segluromet).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30938372", "endSection": "abstract" }, { "offsetInBeginSection": 356, "offsetInEndSection": 599, "text": "Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30724637", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 662, "text": "Ertugliflozin and fixed-dose combinations of ertugliflozin and metformin (Segluromet\u2122) and ertugliflozin and sitagliptin (Steglujan\u2122) have recently been approved by the US FDA as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29476348", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 661, "text": "Ertugliflozin and fixed-dose combinations of ertugliflozin and metformin (Segluromet\u2122) and ertugliflozin and sitagliptin (Steglujan\u2122) have recently been approved by the US FDA as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29476348", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 606, "text": "It was granted approval by the U.S. Food and Drug Administration (FDA) in December 2017 for treatment of T2DM as a monotherapy, and as part of two separate fixed-dose combination therapies with sitagliptin (Steglujan) and metformin (Segluromet).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30938372", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 591, "text": "poglycemia. Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and met", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30724637", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 672, "text": "iflozin and fixed-dose combinations of ertugliflozin and metformin (Segluromet\u2122) and ertugliflozin and sitagliptin (Steglujan\u2122) have recently been approved by the US FDA as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM. These prod", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29476348", "endSection": "abstract" }, { "offsetInBeginSection": 369, "offsetInEndSection": 618, "text": "ranted approval by the U.S. Food and Drug Administration (FDA) in December 2017 for treatment of T2DM as a monotherapy, and as part of two separate fixed-dose combination therapies with sitagliptin (Steglujan) and metformin (Segluromet). Ertuglifloz", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30938372", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 605, "text": "Food and Drug Administration (FDA) in December 2017 for treatment of T2DM as a monotherapy, and as part of two separate fixed-dose combination therapies with sitagliptin (Steglujan) and metformin (Segluromet)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30938372", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 660, "text": "Ertugliflozin and fixed-dose combinations of ertugliflozin and metformin (Segluromet\u2122) and ertugliflozin and sitagliptin (Steglujan\u2122) have recently been approved by the US FDA as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29476348", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 584, "text": "hypoglycemia. Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30724637", "endSection": "abstract" } ] }, { "body": "Where is the protein \"Single-stranded DNA-binding protein\" found?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33847964", "http://www.ncbi.nlm.nih.gov/pubmed/33847967", "http://www.ncbi.nlm.nih.gov/pubmed/34215584", "http://www.ncbi.nlm.nih.gov/pubmed/34185867", "http://www.ncbi.nlm.nih.gov/pubmed/34539752" ], "ideal_answer": [ "In the mitochondrion (mitochondrial single-stranded DNA binding protein, mtSSB) and its role is the regulation of mitochondrial DNA replication initiation in mammalian mitochondria." ], "exact_answer": [ "Mitochondrion" ], "type": "factoid", "id": "624c919ee764a53204000004", "snippets": [ { "offsetInBeginSection": 379, "offsetInEndSection": 440, "text": "the mitochondrial single-stranded DNA-binding protein (mtSSB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34539752", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "We report a role for the mitochondrial single-stranded DNA binding protein (mtSSB) in regulating mitochondrial DNA (mtDNA) replication initiation in mammalian mitochondria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34215584", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 69, "text": "SSB1, a Mitochondrial Single-Stranded DNA-Binding Protein", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34185867", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "The mitochondrial single-stranded DNA-binding protein (mtSSB)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33847964", "endSection": "abstract" }, { "offsetInBeginSection": 416, "offsetInEndSection": 468, "text": " mitochondrial single-stranded DNA-binding protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33847967", "endSection": "abstract" } ] }, { "body": "Is periampullary carcinoma (PAC) a relatively rare genitourinary malignancy", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24650967", "http://www.ncbi.nlm.nih.gov/pubmed/23187842", "http://www.ncbi.nlm.nih.gov/pubmed/10073125", "http://www.ncbi.nlm.nih.gov/pubmed/29504325", "http://www.ncbi.nlm.nih.gov/pubmed/33227091", "http://www.ncbi.nlm.nih.gov/pubmed/30258276", "http://www.ncbi.nlm.nih.gov/pubmed/34673588", "http://www.ncbi.nlm.nih.gov/pubmed/24075520" ], "ideal_answer": [ "Periampullary carcinoma (PAC) a relatively rare gastrointestinal malignancy and includes Pancreaticobiliary as a subtype of Periampullary carcinoma" ], "exact_answer": "no", "type": "yesno", "id": "625374a8e764a53204000027", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 135, "text": "Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34673588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "MUC1, CK20, and CDX2 immunohistochemical markers can sub-classify periampullary carcinomas into pancreaticobiliary, intestinal, and mixed subtypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34673588", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Pancreaticoduodenectomy (PD) is a complex surgical procedure involving resection of the duodenum, the pancreatic head and uncinate process, and the distal common bile duct. It is most commonly performed for periampullary malignancy but may also be indicated in select cases of chronic pancreatitis or benign periampullary tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23187842", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 162, "text": "In patients suspected of pancreatic or periampullary cancer, abdominal contrast-enhanced computed tomography (CT) is the standard diagnostic modality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650967", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 275, "text": "The pre-operative neutrophil-to-lymphocyte ratio (NLR), when \u22655 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24075520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Comparison Of Biliary Stenting And Surgical Bypass In Palliative Management Of Irresectable Periampullary Carcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29504325", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 173, "text": " Some 20-40% of the periampullary carcinoma is irresectable at the time of diagnosis. Biliary stenting and surgical bypass are commonly used palliative procedure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29504325", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 395, "text": "Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30258276", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 379, "text": "DEFINITION: Periampullary carcinomas are rare and constitute a special entity, as diagnosed earlier and having a better prognosis than other duodenal tumors.METHODS: In the present study, we retrospectively reviewed the medical records of 16 patients with periampullary carcinomas over 10 years.RESULTS: 16 patients, 10 men and 6 women (median age 66.7 years, range 42-80) had a ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10073125", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Periampullary carcinomas: a special entity of duodenal tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10073125", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33227091", "endSection": "abstract" } ] }, { "body": "For which indication has inotersen been approved?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32865784" ], "ideal_answer": [ "Inoteresen has been approved for patients in stage 1 and stage 2 hereditary transthyretin amyloidosis polyneuropathy." ], "exact_answer": [ "stage 1 and stage 2 hereditary transthyretin amyloidosis polyneuropathy" ], "type": "factoid", "id": "626aed2fe764a53204000043", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Inotersen for the Treatment of Hereditary Transthyretin Amyloidosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32865784", "endSection": "title" }, { "offsetInBeginSection": 448, "offsetInEndSection": 719, "text": "A new drug named inotersen (brand name Tagsedi), also known as IONIS-TTRRX, has been approved by the United States Food and Drug Agency, Health Canada, and European Commission in 2018, and introduced to the market for patients in stage 1 and stage 2 hATTR polyneuropathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32865784", "endSection": "abstract" } ] }, { "body": "Do SETD1A mutations predispose to schizophrenia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31606247" ], "ideal_answer": [ "Yes. There is a mutation in the gene that codes for a protein called SetD1A. This protein is involved in the development of schizophrenia.", "Yes. SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits." ], "exact_answer": "yes", "type": "yesno", "id": "62015485c9dfcb9c09000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31606247", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1135, "text": "SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. We show that Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets\u00a0are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits. Finally, we identify LSD1 as a major counteracting demethylase for Setd1a and show that its pharmacological antagonism results in a full rescue of the behavioral and morphological deficits in Setd1a-deficient mice. Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31606247", "endSection": "abstract" } ] }, { "body": "Is Sotatercept effective for Pulmonary Arterial Hypertension?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33789009", "http://www.ncbi.nlm.nih.gov/pubmed/33733610" ], "ideal_answer": [ "Sotatercept was shown to be effective for Pulmonary Arterial Hypertension." ], "exact_answer": "yes", "type": "yesno", "id": "61f7cca7882a024a1000002b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Sotatercept for the Treatment of Pulmonary Arterial Hypertension.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789009", "endSection": "title" }, { "offsetInBeginSection": 1920, "offsetInEndSection": 2094, "text": "CONCLUSIONS: Treatment with sotatercept resulted in a reduction in pulmonary vascular resistance in patients receiving background therapy for pulmonary arterial hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Sotatercept for the Treatment of Pulmonary Arterial Hypertension", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789009", "endSection": "title" }, { "offsetInBeginSection": 1920, "offsetInEndSection": 2092, "text": "CONCLUSIONS: Treatment with sotatercept resulted in a reduction in pulmonary vascular resistance in patients receiving background therapy for pulmonary arterial hypertensio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789009", "endSection": "abstract" }, { "offsetInBeginSection": 1821, "offsetInEndSection": 2051, "text": "n hematologic adverse events. One patient in the sotatercept 0.7-mg group died from cardiac arrest.CONCLUSIONS: Treatment with sotatercept resulted in a reduction in pulmonary vascular resistance in patients receiving background t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33789009", "endSection": "abstract" } ] }, { "body": "Which disease is caused by mutations in the gene CALR?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32733014", "http://www.ncbi.nlm.nih.gov/pubmed/33202418", "http://www.ncbi.nlm.nih.gov/pubmed/34571965", "http://www.ncbi.nlm.nih.gov/pubmed/33202112", "http://www.ncbi.nlm.nih.gov/pubmed/34804436", "http://www.ncbi.nlm.nih.gov/pubmed/32694616" ], "ideal_answer": [ "Somatic mutations of calreticulin (CALR) have been identified as a main disease driver of myeloproliferative neoplasms," ], "exact_answer": [ "myeloproliferative neoplasms" ], "type": "factoid", "id": "623e04e4f0baec9a1b000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "JAK2, CALR, and MPL are myeloproliferative neoplasm (MPN)-driver mutations,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32694616", "endSection": "abstract" }, { "offsetInBeginSection": 696, "offsetInEndSection": 748, "text": " loss-of-function CALR mutations promote oncogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32733014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34571965", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Classification of myeloproliferative neoplasms is based on hematologic, histopathologic, and molecular characteristics, including the BCR-ABL1 and JAK2 V617F or MPL and CALR. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34804436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "AIMS: JAK2V617F (JAK2), calreticulin (CALR) and MPL515L/K (MPL) mutations are important in essential thrombocythemia (ET) and may be associated with various clinical consequences of the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Somatic mutations of calreticulin (CALR) have been identified as a main disease driver of myeloproliferative neoplasms,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33202418", "endSection": "abstract" } ] }, { "body": "Is the 22-item sino-nasal outcome test (SNOT-22) a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34196397", "http://www.ncbi.nlm.nih.gov/pubmed/26228968", "http://www.ncbi.nlm.nih.gov/pubmed/30156212", "http://www.ncbi.nlm.nih.gov/pubmed/28753732", "http://www.ncbi.nlm.nih.gov/pubmed/31306495", "http://www.ncbi.nlm.nih.gov/pubmed/34182821", "http://www.ncbi.nlm.nih.gov/pubmed/33271403", "http://www.ncbi.nlm.nih.gov/pubmed/34585521", "http://www.ncbi.nlm.nih.gov/pubmed/31608679", "http://www.ncbi.nlm.nih.gov/pubmed/33657861", "http://www.ncbi.nlm.nih.gov/pubmed/19793277", "http://www.ncbi.nlm.nih.gov/pubmed/33906469", "http://www.ncbi.nlm.nih.gov/pubmed/25195715", "http://www.ncbi.nlm.nih.gov/pubmed/34437720", "http://www.ncbi.nlm.nih.gov/pubmed/26610073", "http://www.ncbi.nlm.nih.gov/pubmed/25323055" ], "ideal_answer": [ "Conclusion. The German-SNOT-22 validated here matches the original SNOT-22. It is a reliable, valid and responsive questionnaire to assess symptoms, HRQOL and treatment-response in CRS-patients.", "The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS)", "The SNOT-22 is a reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS).", "Yes, the 22-item sino-nasal outcome test (SNOT-22) is a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS).", "The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS)." ], "exact_answer": "yes", "type": "yesno", "id": "624f2355e764a5320400000b", "snippets": [ { "offsetInBeginSection": 9, "offsetInEndSection": 218, "text": "The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Assessment of health-related quality-of-life in patients with chronic Rhinosinusitis - Validation of the German Sino-Nasal Outcome Test-22 (German-SNOT-22).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271403", "endSection": "title" }, { "offsetInBeginSection": 457, "offsetInEndSection": 722, "text": " Patients meeting diagnostic criteria for CRS were prospectively enrolled in a cross-sectional study. Responses from the Sinonasal Outcomes Test-22 (SNOT-22), a measure of patient HRQOL, as well as the Lund-Kennedy and Lund-Mackay scores were recorded at enrollment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33906469", "endSection": "abstract" }, { "offsetInBeginSection": 296, "offsetInEndSection": 648, "text": "Three groups of 12 participants each were examined: patients with CRS without polyposis (CRS group), patients with symptoms of CRS but radiologically normal sinuses (symptoms-only), and healthy controls. Measurements of nNO were carried out using aspiration method and humming maneuver. All participants completed the Sino-Nasal Outcome Test (SNOT-22).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31608679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "PURPOSE: The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271403", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1084, "text": "tcomes included scores on the CRS disease severity visual analog scale (VAS), 22-item Sino-Nasal Outcome Test (SNOT-22), 5-dimension EuroQoL (EQ-5D) general health status VAS, and 36-item Short-Form Health Survey (SF-36) for HRQoL and nasal polyp-related healthcare resource use questionnaires.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31306495", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND: The 22-item Sino-Nasal Outcome Test (SNOT-22) is a commonly utilized outcome measure for chronic rhinosinus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26610073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND: The 22-item sino-nasal outcome test (SNOT-22) is a widely used and powerful patient-reported outcomes measure for chronic rhinosinus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "BACKGROUND: Prior study demonstrated that baseline 22-item Sino-Nasal Outcome Test (SNOT-22) aggregate scores accurately predict selection of surgical intervention in patients with chronic rhinosinus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25323055", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "OBJECTIVES/HYPOTHESIS: Sinonasal Outcomes Test-22 (SNOT-22) is used widely as a patient-reported sinonasal quality-of-life (QOL) instrument for endoscopic endonasa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34196397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Is sino-nasal outcome test-22 reliable for guiding chronic rhinosinusitis patients for endoscopic sinus surgery", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30156212", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The Sino-Nasal Outcome Test-22 as a tool to identify chronic rhinosinusitis in adults with cystic fibrosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26228968", "endSection": "title" }, { "offsetInBeginSection": 287, "offsetInEndSection": 426, "text": "rden. Our objective was to investigate the utility of the 22-item Sino-Nasal Outcome Test (SNOT-22) as a tool to identify CRS in adults wit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26228968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34437720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "OBJECTIVE: The SNOT-22 (22-item Sinonasal Outcome Test) is a high-quality outcome measure that assesses chronic rhinosinusitis-specific quality of lif", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34182821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: The 22-item sino-nasal outcome test (SNOT-22) is a widely used and powerful patient-reported outcomes measure for chronic rhinosinusitis (CRS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nasal polyps (CRSwNP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34437720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "BACKGROUND: The 22-item Sino-Nasal Outcome Test (SNOT-22) is a commonly utilized outcome measure for chronic rhinosinusitis (CRS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26610073", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 612, "text": "OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nasal polyps (CRSwNP).STUDY DESIGN: Validation of SNOT-22 domain structure, using data from 3 randomized, placebo-controlled, double-blinded, multicenter clinical trials of dupilumab in adults with moderate-to-severe CRSwNP.METHODS: Preliminary dimensional structure was derived by exploratory factor analyses of SNOT-22 data from a phase 2 trial (NCT01920", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34437720", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 483, "text": "OBJECTIVES: We set out to determine the psychometric validation of a disease-specific health related quality of life instrument for use in chronic rhinosinusitis, the 22 item Sinonasal Outcome Test (SNOT-22), a modification of a pre-existing instrument, the SNOT-20.DESIGN, SETTING AND PARTICIPANTS: The National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis was a prospective cohort study collecting data on 3128 adult patients undergoing sinonasal sur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "OBJECTIVE: The SNOT-22 (22-item Sinonasal Outcome Test) is a high-quality outcome measure that assesses chronic rhinosinusitis-specific quali", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34182821", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 308, "text": "act of CRS. We sought to determine if 22-item Sino-Nasal Outcome Test (SNOT-22) score is predictive of patient-perceived CRS symptom control.METHODS: Prospective cross-sectional study of 2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28753732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "The Sinonasal Outcome Test (SNOT-22) Is a Poor Diagnostic Tool for Chronic Rhinosinusitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33657861", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "The 22-item Sino-Nasal Outcome Test accurately reflects patient-reported control of chronic rhinosinusitis symptomatology.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28753732", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Development of Sinonasal Outcome Test (SNOT-22) Domains in Chronic Rhinosinusitis With Nasal Polyps.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34437720", "endSection": "title" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1643, "text": "cture with strong Cronbach's alpha values (all >0.80). Moderate-to-high correlations were observed between change in SNOT-22 domain scores and other study patient-reported outcome measures, along with large effect-size estimates (\u22650.7), demonstrating re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34437720", "endSection": "abstract" } ] }, { "body": "Is pRETRO-SUPER an adenoviral vector?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24168513" ], "ideal_answer": [ "No, pRETRO-SUPER is a retroviral vector." ], "exact_answer": "no", "type": "yesno", "id": "626aa563e764a53204000036", "snippets": [ { "offsetInBeginSection": 10, "offsetInEndSection": 369, "text": " In this study, we investigated the effect of small interfering RNA (siRNA) of connective tissue growth factor (CTGF) by pRetro-Super (PRS) retrovirus vector on the expression of CTGF and related extracellular matrix molecules in human renal proximal tubular cells (HKCs) induced by high glucose, to provide help for renal tubulointerstitial fibrosis therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24168513", "endSection": "abstract" } ] }, { "body": "Which tool has been developed for annotation of G\u03b1, G\u03b2 and G\u03b3 subunits of G-proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26854601" ], "ideal_answer": [ "GprotPRED is an online tool that uses profile Hidden Markov Models (pHMMs) and application to proteomes. The sensitivity and specificity for all pHMMs were equal to 100% with the exception of the G\u03b2 case, where sensitivity equals to 100%, while specificity is 99.993%.", "GprotPRED is a tool that has been developed for annotation of G\u03b1, G\u03b2 and G\u03b3 subunits of G-proteins using profile Hidden Markov Models (pHMMs)." ], "exact_answer": [ "GprotPRED" ], "type": "factoid", "id": "62005c68c9dfcb9c09000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "GprotPRED: Annotation of G\u03b1, G\u03b2 and G\u03b3 subunits of G-proteins using profile Hidden Markov Models (pHMMs) and application to proteomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26854601", "endSection": "title" }, { "offsetInBeginSection": 883, "offsetInEndSection": 1583, "text": "An online tool, GprotPRED, was developed that uses these six pHMMs. The sensitivity and specificity for all pHMMs were equal to 100% with the exception of the G\u03b2 case, where sensitivity equals to 100%, while specificity is 99.993%. In contrast to Pfam's pHMM which detects G\u03b1 subunits in general, our method not only detects G\u03b1 subunits but also classifies them into the appropriate G\u03b1-protein family and thus could become a useful tool for the annotation of G-proteins in newly discovered proteomes. GprotPRED online tool is publicly available for non-commercial use at http://bioinformatics.biol.uoa.gr/GprotPRED and, also, a standalone version of the tool at https://github.com/vkostiou/GprotPRED.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26854601", "endSection": "abstract" } ] }, { "body": "Describe applications of the CHALICE rule?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23015114", "http://www.ncbi.nlm.nih.gov/pubmed/30277194", "http://www.ncbi.nlm.nih.gov/pubmed/24927811", "http://www.ncbi.nlm.nih.gov/pubmed/20573733", "http://www.ncbi.nlm.nih.gov/pubmed/17056862", "http://www.ncbi.nlm.nih.gov/pubmed/21310894", "http://www.ncbi.nlm.nih.gov/pubmed/30833284", "http://www.ncbi.nlm.nih.gov/pubmed/26584662", "http://www.ncbi.nlm.nih.gov/pubmed/20659884", "http://www.ncbi.nlm.nih.gov/pubmed/29452747", "http://www.ncbi.nlm.nih.gov/pubmed/23968775" ], "ideal_answer": [ "The children's head injury algorithm for the prediction of important clinical events (CHALICE) is one of the strongest clinical prediction rules for the management of children with head injuries. It can be used to predict death, need for neurosurgical intervention or CT abnormality in children with head trauma." ], "type": "summary", "id": "6200896bc9dfcb9c09000022", "snippets": [ { "offsetInBeginSection": 536, "offsetInEndSection": 989, "text": "RESULTS: The optimal strategy was based on the Children's Head injury Algorithm for the prediction of Important Clinical Events (CHALICE) rule, although the costs and outcomes associated with each strategy were broadly similar.CONCLUSIONS: Liberal use of CT scanning based on a high sensitivity decision rule is not only effective but also cost saving, with the CHALICE rule being the optimal strategy, although there is some uncertainty in the results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23968775", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1222, "text": "For neurosurgical injury all had high sensitivity (98-100%) but the children's head injury algorithm for the prediction of important clinical events (CHALICE) rule had the highest specificity (86%) in its derivation cohort", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21310894", "endSection": "abstract" }, { "offsetInBeginSection": 1450, "offsetInEndSection": 1653, "text": "Application of this rule in the UK would probably result in an unacceptably high rate of CT scans per injury, and continued use of the CHALICE-based NICE guidelines represents an appropriate alternative.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21310894", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Application of the CHALICE clinical prediction rule for intracranial injury in children outside the UK: impact on head CT rate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573733", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "OBJECTIVE: The children's head injury algorithm for the prediction of important clinical events (CHALICE) is one of the strongest clinical prediction rules for the management of children with head injuries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573733", "endSection": "abstract" }, { "offsetInBeginSection": 1344, "offsetInEndSection": 1521, "text": "CONCLUSIONS: Application of the CHALICE rule to this non-UK dataset would double the proportion of CT scans, with an apparent small gain in delayed pick-up of CT abnormalities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573733", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 921, "text": "These variables were defined from a literature review, and a pilot study was conducted before the children's head injury algorithm for the prediction of important clinical events (CHALICE) study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17056862", "endSection": "abstract" }, { "offsetInBeginSection": 1432, "offsetInEndSection": 1685, "text": "The CHALICE rule was derived with a sensitivity of 98% (95% confidence interval (CI) 96% to 100%) and a specificity of 87% (95% CI 86% to 87%) for the prediction of clinically significant head injury, and requires a computed tomography scan rate of 14%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17056862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Clinical questionWhat is the diagnostic accuracy of the PECARN, CATCH, and CHALICE clinical decision rules for pediatric head injury, and are the clinical decision rules valid when applied to a novel data set?Article chosenBabl FE, Borland ML, Phillips N, et al.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30277194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Comparison of PECARN, CATCH, and CHALICE clinical decision rules for pediatric head injury in the emergency department.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30277194", "endSection": "title" }, { "offsetInBeginSection": 137, "offsetInEndSection": 402, "text": "Those of the highest quality are the Canadian assessment of tomography for childhood head injury (CATCH), Children's head injury algorithm for the prediction of important clinical events (CHALICE) and Pediatric Emergency Care Applied Research Network (PECARN) CDRs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Applicability of the CATCH, CHALICE and PECARN paediatric head injury clinical decision rules: pilot data from a single Australian centre.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23015114", "endSection": "title" }, { "offsetInBeginSection": 458, "offsetInEndSection": 733, "text": "edictor variables used in the Canadian Assessment of Tomography for Childhood Head Injury (CATCH), Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) and Pediatric Emergency Care Applied Research Network (PECARN) CDRs were collected. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26584662", "endSection": "abstract" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1227, "text": "neurosurgical injury all had high sensitivity (98-100%) but the children's head injury algorithm for the prediction of important clinical events (CHALICE) rule had the highest specificity (86%) in its derivation cohort.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21310894", "endSection": "abstract" }, { "offsetInBeginSection": 540, "offsetInEndSection": 767, "text": "LTS: The optimal strategy was based on the Children's Head injury Algorithm for the prediction of Important Clinical Events (CHALICE) rule, although the costs and outcomes associated with each strategy were broadly similar.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23968775", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 361, "text": "This is based on the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) head injury rule.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20659884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "OBJECTIVE: The children's head injury algorithm for the prediction of important clinical events (CHALICE) is one of the strongest clinical prediction rules for the management of children with head ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573733", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "STUDY OBJECTIVE: Three clinical decision rules for head injuries in children (Pediatric Emergency Care Applied Research\u00a0Network [PECARN], Canadian Assessment of Tomography for Childhood Head Injury [CATCH], and Children's Head Injury Algorithm for the Prediction of Important Clinical Events [CHALICE]) have been shown to have\u00a0high performance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29452747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Clinical questionWhat is the diagnostic accuracy of the PECARN, CATCH, and CHALICE clinical decision rules for pediatric head injury, and are the clinical decision rules valid when applied to a novel data set?Ar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30277194", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 464, "text": "icult. We determined the risk of intracranial injury when SH is the only predictor variable using definitions from the Pediatric Emergency Care Applied Research Network (PECARN) and Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) head trauma rul", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30833284", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 352, "text": "with this. This is based on the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) head inj", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20659884", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 669, "text": "ary objective of the study was to determine the diagnostic accuracy and provide external validation for the PECARN, CATCH, and CHALICE clinical decision rules in a clinically homogeneous cohort of children. The secondary objecti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30277194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Clinical questionWhat is the diagnostic accuracy of the PECARN, CATCH, and CHALICE clinical decision rules for pediatric head injury, and are the clinical decision rules valid when applied to a novel data set?Article chosenBabl FE, Borland ML, Phillips N, et al", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30277194", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 1073, "text": " Three rules have been identified as being of high quality and accuracy: the Canadian Assessment of Tomography for Childhood Head Injury (CATCH) from Canada, the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) from the UK, and the prediction rule for the identification of children at very low risk of clinically important traumatic brain injury developed by the Pediatric Emergency Care Applied Research Network (PECARN) from the US", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24927811", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 729, "text": " Predictor variables used in the Canadian Assessment of Tomography for Childhood Head Injury (CATCH), Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) and Pediatric Emergency Care Applied Research Network (PECARN) CDRs were collecte", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26584662", "endSection": "abstract" }, { "offsetInBeginSection": 1398, "offsetInEndSection": 1805, "text": "rosurgical operation and 15 died. The CHALICE rule was derived with a sensitivity of 98% (95% confidence interval (CI) 96% to 100%) and a specificity of 87% (95% CI 86% to 87%) for the prediction of clinically significant head injury, and requires a computed tomography scan rate of 14%.CONCLUSION: A highly sensitive clinical decision rule is derived for the identification of children who should undergo c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17056862", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "OBJECTIVE: The children's head injury algorithm for the prediction of important clinical events (CHALICE) is one of the strongest clinical prediction rules for the management of children with hea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20573733", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 1250, "text": "difficult. We determined the risk of intracranial injury when SH is the only predictor variable using definitions from the Pediatric Emergency Care Applied Research Network (PECARN) and Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) head trauma rules.DESIGN: Planned secondary analysis of a multicentre prospective observational study.SETTING: Ten emergency departments in Australia and New Zealand.PATIENTS: Children <2 years with head trauma (n=5237).INTERVENTIONS: We used the PECARN (any non-frontal haematoma) and CHALICE (>5\u2009cm haematoma in any region of the head) rule-based definition of isolated SH in both children <1\u2009year and <2 years.MAIN OUTCOME MEASURES: Clinically important traumatic brain injury (ciTBI; ie, death, neurosurgery, intubation >24\u2009hours or positive CT scan in association with hospitalisation \u22652 nights for traumatic brain injury).RESULTS: In children <1\u2009year with isolated SH as per PECARN rule, the risk of ciTBI was 0.0% (0/109; 95% CI 0.0% to 3.3%); in those with isolated SH as defined by the CHALIC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30833284", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 369, "text": "Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30277194", "endSection": "abstract" } ] }, { "body": "What is the KDEL retention signal?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10767987", "http://www.ncbi.nlm.nih.gov/pubmed/7893163", "http://www.ncbi.nlm.nih.gov/pubmed/28669732", "http://www.ncbi.nlm.nih.gov/pubmed/29733248", "http://www.ncbi.nlm.nih.gov/pubmed/32020276" ], "ideal_answer": [ "the -KDEL retention signal sequence is characteristic of many proteins localized to the ER." ], "exact_answer": [ "ER retention sequence (KDEL)" ], "type": "factoid", "id": "623e02e0f0baec9a1b000005", "snippets": [ { "offsetInBeginSection": 901, "offsetInEndSection": 1092, "text": "By fusing the antibody with a KDEL retention signal, the interaction of antibodies and native membrane antigens occurs inside the endoplasmic reticulum during the process of protein secretion", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32020276", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 425, "text": "ER retention sequence (KDEL)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29733248", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 527, "text": " The KDEL retention signal led to the accumulation of PrP in the ER, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28669732", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 507, "text": "retained in the endoplasmic reticulum (ER) using a KDEL retention signal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10767987", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 362, "text": " These sequences are similar to the -KDEL retention signal sequence characteristic of many proteins localized to the ER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7893163", "endSection": "abstract" } ] }, { "body": "What are the diagnostic criteria for hemophagocytic lymphohistiocytosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32300936", "http://www.ncbi.nlm.nih.gov/pubmed/16937360", "http://www.ncbi.nlm.nih.gov/pubmed/32588191", "http://www.ncbi.nlm.nih.gov/pubmed/30086677", "http://www.ncbi.nlm.nih.gov/pubmed/26512263", "http://www.ncbi.nlm.nih.gov/pubmed/24583560", "http://www.ncbi.nlm.nih.gov/pubmed/33658450", "http://www.ncbi.nlm.nih.gov/pubmed/34850652", "http://www.ncbi.nlm.nih.gov/pubmed/1561489", "http://www.ncbi.nlm.nih.gov/pubmed/21773661" ], "ideal_answer": [ "Hemophagocytic syndrome (HS) is a severe hyper inflammatory condition whose cardinal symptoms are prolonged fever, cytopenia, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages.", "Hemophagocytic lymphohistiocytosis (HLH), diagnosis is based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis)." ], "exact_answer": [ [ "fever" ], [ "splenomegaly" ], [ "bicytopenia" ], [ "hypertriglyceridemia" ], [ "hypofibrinogenemia" ], [ "hemophagocytosis" ], [ "hyperferritinemia" ], [ "excessive cytokine production" ], [ "hepatosplenomegaly" ], [ "Hemophagocytic lymphohistiocytosis is a rare and aggressive syndrome of excessive cytokine requiring prompt recognition and aggressive therapy." ] ], "type": "list", "id": "625ebd06e764a53204000031", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 161, "text": "Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome of excessive cytokine requiring prompt recognition and aggressive therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32300936", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 408, "text": "Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that is characterized by an overactive response of the immune system with excessive production of proinflammatory cytokines. Initial presentation of this condition often mimics and overlaps with many diseases including infections, sepsis, and multiorgan failure syndrome, which makes diagnosis the diagnosis of HLH challenging", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34850652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32588191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Hemophagocytic syndrome (HS) is a severe hyper inflammatory condition whose cardinal symptoms are prolonged fever, cytopenia, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21773661", "endSection": "abstract" }, { "offsetInBeginSection": 59, "offsetInEndSection": 310, "text": "Acquired hemophagocytic lymphohistiocytosis comprises a heterogenous group of hyperinflammatory immunoreactions often resulting in uncontrolled immune responses, mainly throughout proliferation of cytotoxic T cells and hemophagocytosis by macrophages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30086677", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1136, "text": " and symptoms fulfilled the five criteria for a diagnosis of hemophagocytic lymphohistiocytosis, including fever, cytopenia, hemophagocytosis, hyperferritinemia, and high soluble interleukin-2 receptor levels. Therefore, the d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33658450", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 902, "text": "ostic criteria of hemophagocytic lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and hyperferritinemia, elevated serum level of soluble interleukin-2 receptor (sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased cytotoxic T cell and natural killer cell activity. In this cas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24583560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "In HLH-94, the first prospective international treatment study for hemophagocytic lymphohistiocytosis (HLH), diagnosis was based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). In HL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16937360", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 451, "text": "Diagnostic criteria include idiopathic fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and the presence of hemophagocytosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1561489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, splenomegaly, jaundice, and pathologic findings of hemophagocytosis in bone marrow or other tissues such as the lymph nodes and liver", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26512263", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 890, "text": "Diagnostic criteria of hemophagocytic lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and hyperferritinemia, elevated serum level of soluble interleukin-2 receptor (sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased cytotoxic T cell and natural killer cell activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24583560", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 452, "text": "Diagnostic criteria include idiopathic fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and the presence of hemophagocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1561489", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "In HLH-94, the first prospective international treatment study for hemophagocytic lymphohistiocytosis (HLH), diagnosis was based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16937360", "endSection": "abstract" } ] }, { "body": "When was Vitravene approved in Brazil?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11497353" ], "ideal_answer": [ "Vitravene was approved in Brazil in the summer of 1999." ], "exact_answer": [ "1999" ], "type": "factoid", "id": "626aef83e764a53204000044", "snippets": [ { "offsetInBeginSection": 486, "offsetInEndSection": 701, "text": "In August 1998, the FDA approved the marketing of Vitravene for the local treatment of CMV retinitis [296420], [296780], and both European and Brazilian registration approval followed in the summer of 1999 [335238].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11497353", "endSection": "abstract" } ] }, { "body": "Is there a dependence between chromatin organization and dorsoventral gene expression in Drosophila?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33795866" ], "ideal_answer": [ "No. There is independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning", "No. There is evidence for the independence of chromatin organization and dorsoventral gene expression in Drosophila. Tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active." ], "exact_answer": "no", "type": "yesno", "id": "6201a85cc9dfcb9c0900002a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33795866", "endSection": "title" }, { "offsetInBeginSection": 503, "offsetInEndSection": 1144, "text": "Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33795866", "endSection": "abstract" } ] }, { "body": "Is vocimagene amiretrorepvec effective for recurrent high-grade glioma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30676111", "http://www.ncbi.nlm.nih.gov/pubmed/29117980", "http://www.ncbi.nlm.nih.gov/pubmed/27252174", "http://www.ncbi.nlm.nih.gov/pubmed/33119048" ], "ideal_answer": [ "No. Despite initially promising results in a randomized, open-label phase 2/3 trial, among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC did not improve overall survival or other efficacy end points." ], "exact_answer": "no", "type": "yesno", "id": "61faa1fcc9dfcb9c0900000a", "snippets": [ { "offsetInBeginSection": 2183, "offsetInEndSection": 2434, "text": "Relevance: Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33119048", "endSection": "abstract" }, { "offsetInBeginSection": 1845, "offsetInEndSection": 2075, "text": "The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P\u2009=\u2009.62). The secondary end points did not demonstrate statistically significant differences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33119048", "endSection": "abstract" }, { "offsetInBeginSection": 633, "offsetInEndSection": 867, "text": "Expert opinion: These early studies provide very encouraging results for Toca 511 and Toca FC in rHGG. This therapy had a response rate of 11.3% and a mOS of 11.9\u00a0months in 56 patients, an improvement compared to historical controls. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30676111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "Findings from a phase I study suggest that delivering high concentrations of the chemotherapy 5-FU directly to brain tumors via the retroviral vector vocimagene amiretrorepvec, or Toca 511, may benefit patients with recurrent high-grade glioma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29117980", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 794, "text": "Overall survival for recurrent high-grade glioma was 13.6 months (95% confidence interval, 10.8 to 20.0) and was statistically improved relative to an external control (hazard ratio, 0.45; P = 0.003).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27252174", "endSection": "abstract" } ] }, { "body": "Which proteins are markers of myositis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34571335", "http://www.ncbi.nlm.nih.gov/pubmed/33416262", "http://www.ncbi.nlm.nih.gov/pubmed/34030894" ], "ideal_answer": [ "Blood tests showed significantly increased CK and aldolase values in patients with myositis (p < 0.001 and p < 0.0001)." ], "exact_answer": [ [ "CK" ], [ "Aldolase" ] ], "type": "list", "id": "624de153e764a53204000007", "snippets": [ { "offsetInBeginSection": 326, "offsetInEndSection": 441, "text": "Biological markers such as serum creatine phosphokinase (CPK) are commonly used to measure muscular tissue injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34571335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Cardiac Troponin I and T in Checkpoint Inhibitor-associated Myositis and Myocarditis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33416262", "endSection": "title" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1103, "text": "Blood tests showed significantly increased CK and aldolase values in patients with myositis (p < 0.001 and p < 0.0001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34030894", "endSection": "abstract" } ] }, { "body": "What is the association between maternal and fetal alloantigens and RANTES production?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9886550", "http://www.ncbi.nlm.nih.gov/pubmed/17076674", "http://www.ncbi.nlm.nih.gov/pubmed/17217369" ], "ideal_answer": [ "Induction of maternal tolerance to fetal alloantigens by RANTES production.", "Maternal tolerance to fetal alloantigens may be induced by RANTES production." ], "exact_answer": [ "induction of tolerance" ], "type": "factoid", "id": "623c8330f0baec9a1b000003", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Induction of maternal tolerance to fetal alloantigens by RANTES production.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17076674", "endSection": "title" }, { "offsetInBeginSection": 160, "offsetInEndSection": 245, "text": "we have investigated the role of RANTES in the induction of maternal-fetal tolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17076674", "endSection": "abstract" }, { "offsetInBeginSection": 1061, "offsetInEndSection": 1170, "text": "RANTES may be implicated in the local induction of a Th1-type response necessary for successful implantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17076674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "PROBLEM: Several studies indicate that RANTES (regulated on activation, normal T cell expressed and secreted) is able to downregulate T-cell responses which suggest it might be relevant for fetal tolerance induction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Induction of maternal tolerance to fetal alloantigens by RANTES production", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17076674", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "PROBLEM: Several studies indicate that RANTES (regulated on activation, normal T cell expressed and secreted) is able to downregulate T-cell responses which suggest it might be relevant for fetal tolerance ind", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "PROBLEM: Several studies indicate that RANTES (regulated on activation, normal T cell expressed and secreted) is able to downregulate T-cell responses which suggest it might be relevant for fetal tolerance i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217369", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "Cytokines such as monocyte chemotactic peptide-1 (MCP-1), interleukin-8 (IL-8), RANTES (Regulated on Activation and Normally T-cells Expressed and presumably Secreted) and interleukin-10 (IL-10) are thought to play pivotal roles in immune recognition, acceptance of the fetal allograft, maintenance of pregnancy and parturition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9886550", "endSection": "abstract" } ] }, { "body": "What is Tagsedi?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32865784" ], "ideal_answer": [ "Tagsedi is a second-generation antisense oligonucleotide with 2'-O-methoxyethyl modification designed to bind to the 3' untranslated region of the transthyretin mRNA in the nucleus of the liver cells." ], "type": "summary", "id": "626aec71e764a53204000041", "snippets": [ { "offsetInBeginSection": 448, "offsetInEndSection": 923, "text": "A new drug named inotersen (brand name Tagsedi), also known as IONIS-TTRRX, has been approved by the United States Food and Drug Agency, Health Canada, and European Commission in 2018, and introduced to the market for patients in stage 1 and stage 2 hATTR polyneuropathy. Inotersen is a second-generation antisense oligonucleotide with 2'-O-methoxyethyl modification designed to bind to the 3' untranslated region of the transthyretin mRNA in the nucleus of the liver cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32865784", "endSection": "abstract" } ] }, { "body": "Should perampanel be used for amyotrophic lateral sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34322897", "http://www.ncbi.nlm.nih.gov/pubmed/34191081" ], "ideal_answer": [ "No. Perampanel should not be used for amyotrophic lateral sclerosis." ], "exact_answer": "no", "type": "yesno", "id": "61f93e68882a024a1000004d", "snippets": [ { "offsetInBeginSection": 869, "offsetInEndSection": 1270, "text": "RESULTS: Six participants were enrolled. All had adverse events, mostly behavioral. Two completed the trial and the other four withdrew due to adverse events. All participants reported resolution of these events after discontinuation of the drug. The trial was halted due to the large number of adverse events.DISCUSSION: The use of perampanel in this study of ALS was limited by its poor tolerability", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34322897", "endSection": "abstract" }, { "offsetInBeginSection": 1285, "offsetInEndSection": 1438, "text": "CONCLUSIONS: Perampanel was associated with a significant decline in ALSFRS-R score and was linked to worsening of the bulbar subscore in the 8\u00a0mg group.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34191081", "endSection": "abstract" }, { "offsetInBeginSection": 1179, "offsetInEndSection": 1269, "text": "DISCUSSION: The use of perampanel in this study of ALS was limited by its poor tolerabilit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34322897", "endSection": "abstract" } ] }, { "body": "Is Satb1 a transcription factor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34244292", "http://www.ncbi.nlm.nih.gov/pubmed/33834511", "http://www.ncbi.nlm.nih.gov/pubmed/33527899", "http://www.ncbi.nlm.nih.gov/pubmed/34583974" ], "ideal_answer": [ "Yes,\ntranscription factor Satb1." ], "exact_answer": "yes", "type": "yesno", "id": "624c88a1e764a53204000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Special AT-rich sequence binding protein-1 (SATB1) is localized to the nucleus and remodels chromatin structure in T cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34583974", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 240, "text": "chromatin organizers SATB2 and SATB1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34244292", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 568, "text": "transcription factor complexes. These MYB complexes assemble aberrantly with LYL1, E2A, C/EBP family members, LMO2, and SATB1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33527899", "endSection": "abstract" }, { "offsetInBeginSection": 784, "offsetInEndSection": 907, "text": "Staining for the transcription factors Foxp2, Satb1 and Satb2 labeled most ganglion cells in the avian ganglion cell layer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33834511", "endSection": "abstract" } ] }, { "body": "What is PPROM?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/12397216", "http://www.ncbi.nlm.nih.gov/pubmed/32792973", "http://www.ncbi.nlm.nih.gov/pubmed/31018725", "http://www.ncbi.nlm.nih.gov/pubmed/19823961", "http://www.ncbi.nlm.nih.gov/pubmed/17217365", "http://www.ncbi.nlm.nih.gov/pubmed/23536574", "http://www.ncbi.nlm.nih.gov/pubmed/27811444", "http://www.ncbi.nlm.nih.gov/pubmed/34470126", "http://www.ncbi.nlm.nih.gov/pubmed/28710882", "http://www.ncbi.nlm.nih.gov/pubmed/11293640", "http://www.ncbi.nlm.nih.gov/pubmed/23573382", "http://www.ncbi.nlm.nih.gov/pubmed/17206977", "http://www.ncbi.nlm.nih.gov/pubmed/20054828", "http://www.ncbi.nlm.nih.gov/pubmed/28807394", "http://www.ncbi.nlm.nih.gov/pubmed/15715592", "http://www.ncbi.nlm.nih.gov/pubmed/24958400", "http://www.ncbi.nlm.nih.gov/pubmed/29380497", "http://www.ncbi.nlm.nih.gov/pubmed/24010826", "http://www.ncbi.nlm.nih.gov/pubmed/33484479", "http://www.ncbi.nlm.nih.gov/pubmed/8371900", "http://www.ncbi.nlm.nih.gov/pubmed/31056993", "http://www.ncbi.nlm.nih.gov/pubmed/22706240", "http://www.ncbi.nlm.nih.gov/pubmed/23580009", "http://www.ncbi.nlm.nih.gov/pubmed/30957602", "http://www.ncbi.nlm.nih.gov/pubmed/29805914" ], "ideal_answer": [ "Preterm premature(Prelabor) rupture of fetal membranes is often abbreviated as PPROM, and is defined as rupture of membranes before the onset of labor at < 37 weeks' gestation, affects approximately 3% of all pregnancies", "Preterm prelabor rupture of fetal membranes (PPROM) is defined as rupture of membranes before the onset of labor at 37 weeks' gestation, affects approximately 3% of all pregnancies.", "spontaneous preterm premature rupture of fetal membranes (PPROM)." ], "type": "summary", "id": "622a5a483a8413c65300008f", "snippets": [ { "offsetInBeginSection": 92, "offsetInEndSection": 157, "text": "spontaneous preterm premature rupture of fetal membranes (PPROM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30957602", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 173, "text": "preterm prelabor rupture of membranes (PPROM) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31056993", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 308, "text": "preterm prelabor rupture of membranes (PPRoMs).Methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31018725", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 187, "text": "Preterm prelabor rupture of membranes (PPROM), defined as rupture of membranes before the onset of labor at < 37 weeks' gestation, affects approximately 3% of all pregnancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34470126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "OBJECTIVES: To determine whether chorioamniotic membrane separation from the internal cervical os, the \"moon sign,\" is associated with preterm premature rupture of membranes (PPROM) in twin-twin transfusion syndrome (TTTS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24958400", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1247, "text": "Being obese was associated with decreased risks of spontaneous PTD without PPROM <37 weeks (adjusted OR = 0.8, 95% CI: 0.7, 0.9) and increased risk of PPROM <37 weeks (adjusted OR = 1.3, 95% CI: 1.1, 1.6) and PPROM <34 weeks (adjusted OR = 1.4, 95% CI: 1.0, 2.0).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19823961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a leading complication following fetoscopic laser coagulation (FLC) for twin-twin transfusion syndrome (TTTS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29380497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Infection is believed to be a leading cause of preterm premature rupture of membranes (PPROM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12397216", "endSection": "abstract" }, { "offsetInBeginSection": 344, "offsetInEndSection": 582, "text": "lly, we introduce the concept that pPROM is a disease of the fetal membranes where inflammation-oxidative stress axis plays a major role in producing pathways that can lead to membrane weakening through a variety of processes. In addition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28807394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Introduction: Spontaneous preterm birth (sPTB), which predominantly presents as spontaneous preterm labor (sPTL) or prelabor premature rupture of membranes (PPROM), is a syndrome that accounts for 5-10% of live births annu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32792973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "PROBLEM: Preterm, premature rupture of membranes (PPROM) is a dire pregnancy outcome that is frequently associated with infection by the genital mycoplasmas, Mycoplasma hominis, Ureaplasma parvum, and U. urealyticum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17217365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Preterm premature rupture of the membranes (PPROM) is responsible for one-third of all preterm births and affects 120,000 pregnancies in the United States each year", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15715592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Although the etiology of preterm premature rupture of membranes (PPROM) is probably multifactorial, recent literature has indicated that infectious processes may play an important role", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8371900", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "OBJECTION: Preterm premature rupture of membranes (PPROM) is an obstetrics complication and is the leading cause of perinatal mortality and morbidit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23580009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Are biological markers relevant for the diagnosis and the prognosis of preterm premature rupture of membranes (PPROM)?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22706240", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a leading complication following fetoscopic laser coagulation (FLC) for twin-twin transfusion synd", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29380497", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "OBJECTIVES: Preterm premature rupture of membranes (PPROM) is defined as the rupture of fetal membranes befo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23573382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Preterm prelabour rupture of the membranes (PPROM) is defined as prelabour rupture of the membranes prior to 37 weeks of gestation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17206977", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "BACKGROUND: Preterm prelabour rupture of membranes (PPROM) is a common preterm birth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33484479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "BACKGROUND: Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11293640", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28710882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Preterm prelabor rupture of the membranes (pPROM) remains a significant obstetric problem that affects 3-4% of all pregnancies and precedes 40-50% of all preterm births.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28807394", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Preterm premature rupture of membranes (PPROM) is defined as a spontaneous membrane rupture that occurs before the onset of labor and 37 weeks gestation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24010826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Preterm premature rupture of membranes (PPROM) is a challenging complication of pregnancies and an important cause of perinatal morbidity an", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27811444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Preterm premature rupture of the membranes (PPROM) is an important etiology of preterm birth and source of significant neonatal morbidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23536574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Introduction: Pre-term premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29805914", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Preterm premature rupture of the membranes (PPROM) is responsible for one-third of all preterm births and affects 120,000 pregnancies in the United States each year.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15715592", "endSection": "abstract" }, { "offsetInBeginSection": 844, "offsetInEndSection": 1113, "text": "cantly influence the incidence of PPROM. The concordance and predictors of PPROM are maternal age (P < 0.000), gestational age at PROM (P < 0.000), latency period (P < 0.000), and birth weight (P < 0.001).CONCLUSION: PPROM is a major complication of pregnancies and an ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27811444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 633, "text": "OBJECTIVE: To examine the incidence of preterm premature rupture of membranes (PPROM) in pregnancies affected by twin-twin transfusion syndrome (TTTS) treated with laser photocoagulation where an absorbable gelatin sponge was used as a chorioamnion sealant of the fetoscopic access port.METHOD: A retrospective review was undertaken of consecutive cases undergoing fetoscopic directed laser surgery for TTTS between October 2006 and November 2008 at Texas Children's Fetal Center, in which an absorbable gelatin sponge, used as a chorioamnion 'plug', was placed at the conclusion of the intervention as a possible prophylactic measur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20054828", "endSection": "abstract" } ] }, { "body": "What is the half-life of epimutations across generations of C. elegans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31301033", "http://www.ncbi.nlm.nih.gov/pubmed/32868918" ], "ideal_answer": [ "In C. elegans, epimutations typically have short half-lives of two to three generations. Nevertheless, some epimutations last at least ten generations." ], "exact_answer": [ "Typically 2-3 generations. Sometimes >10 generations." ], "type": "factoid", "id": "626ae803e764a5320400003c", "snippets": [ { "offsetInBeginSection": 877, "offsetInEndSection": 1117, "text": "We show that epimutations arise spontaneously at a rate approximately 25 times greater than DNA sequence changes and typically have short half-lives of two to three generations. Nevertheless, some epimutations last at least ten generations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32868918", "endSection": "abstract" } ] }, { "body": "What drugs are included in the Avandamet pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17563269", "http://www.ncbi.nlm.nih.gov/pubmed/17026489", "http://www.ncbi.nlm.nih.gov/pubmed/20840734", "http://www.ncbi.nlm.nih.gov/pubmed/19419339", "http://www.ncbi.nlm.nih.gov/pubmed/25963345", "http://www.ncbi.nlm.nih.gov/pubmed/19105408", "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "http://www.ncbi.nlm.nih.gov/pubmed/16240868", "http://www.ncbi.nlm.nih.gov/pubmed/21682834" ], "ideal_answer": [ "The combination of metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes." ], "exact_answer": [ [ "metformin" ], [ "rosiglitazone" ] ], "type": "list", "id": "61fbc613c9dfcb9c09000010", "snippets": [ { "offsetInBeginSection": 1464, "offsetInEndSection": 1625, "text": "Our method detected the combination of Metformin and Rosiglitazone, which is actually Avandamet, a drug that has been successfully used to treat Type 2 Diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "OBJECTIVE: The long-term cost-effectiveness of using pioglitazone plus metformin (Actoplusmet dagger) compared with rosiglitazone plus metformin (Avandamet double dagger) in treating type 2 diabetes (T2DM) was assessed from a US third-party payer perspective.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19419339", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Metformin/rosiglitazone combination pill (Avandamet) for the treatment of patients with Type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17563269", "endSection": "title" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1499, "text": "The combination of metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17563269", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1498, "text": "The combination of metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17563269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "AIM: This study assessed the efficacy and safety of rosiglitazone and metformin (RSG/MET) fixed-dose combination (AVANDAMET) as initial therapy in patients with uncontrolled type 2 diabetes compared with monotherapy with either RSG or MET after 32 weeks of treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17026489", "endSection": "abstract" }, { "offsetInBeginSection": 1370, "offsetInEndSection": 1518, "text": "metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes. As insulin resistan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17563269", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 833, "text": "single-tablet combination of metformin and rosiglitazone, Avandamet, has become available. Avandamet is ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963345", "endSection": "abstract" }, { "offsetInBeginSection": 1351, "offsetInEndSection": 1497, "text": "The combination of metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17563269", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient complianc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963345", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "AIM: To study effects of avandia and its combination with metformine (avandamet) on secretion of fat tissue hormone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19105408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-na\u00efve type 2 diabetes mellitus patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21682834", "endSection": "title" }, { "offsetInBeginSection": 717, "offsetInEndSection": 818, "text": "Recently, a single-tablet combination of metformin and rosiglitazone, Avandamet, has become available", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "endSection": "abstract" }, { "offsetInBeginSection": 1337, "offsetInEndSection": 1520, "text": "In summary, Avandamet is a single-tablet metformin-rosiglitazone combination that doubly targets insulin resistance as therapy for hyperglycaemia and vascular risk in type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25963345", "endSection": "abstract" }, { "offsetInBeginSection": 717, "offsetInEndSection": 819, "text": "Recently, a single-tablet combination of metformin and rosiglitazone, Avandamet, has become available.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 552, "text": "AIM: This study assessed the efficacy and safety of rosiglitazone and metformin (RSG/MET) fixed-dose combination (AVANDAMET) as initial therapy in patients with uncontrolled type 2 diabetes compared with monotherapy with either RSG or MET after 32 weeks of treatment.METHODS: A total of 468 drug-naive patients with uncontrolled type 2 diabetes were recruited for this multicentre, double-blind trial if their glycated haemoglobin (A1c) was greater than 7.5%, but less than or equal to 11%, and their fasting plasma glucose (FPG) was less than or equal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17026489", "endSection": "abstract" }, { "offsetInBeginSection": 820, "offsetInEndSection": 950, "text": "Avandamet is suitable for type 2 diabetic patients who are inadequately controlled by monotherapy with metformin or rosiglitazone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1336, "text": "Use of Avandamet requires attention to the precautions for both metformin and rosiglitazone, especially renal, cardiac and hepatic competence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Avandamet: combined metformin-rosiglitazone treatment for insulin resistance in type 2 diabetes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15529521", "endSection": "title" }, { "offsetInBeginSection": 1443, "offsetInEndSection": 1877, "text": "eat Type 2 Diabetes. Our method detected the combination of Metformin and Rosiglitazone, which is actually Avandamet, a drug that has been successfully used to treat Type 2 Diabetes.CONCLUSIONS: The results on real biological data demonstrate the effectiveness and efficiency of the proposed method, which can not only detect effective cocktail combination of drugs in an accurate manner but also significantly reduce expensive and te", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20840734", "endSection": "abstract" }, { "offsetInBeginSection": 1006, "offsetInEndSection": 1147, "text": "Finally there are 'fixed combinations of two molecules so as glibenclamide + metformin (Glucovance) or rosiglitazone + metformin (Avandamet).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16240868", "endSection": "abstract" } ] }, { "body": "What does temsirolimus inhibit?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34804848", "http://www.ncbi.nlm.nih.gov/pubmed/31331862", "http://www.ncbi.nlm.nih.gov/pubmed/34589671", "http://www.ncbi.nlm.nih.gov/pubmed/34565342" ], "ideal_answer": [ "Temsirolimus is a mTOR inhibitor" ], "exact_answer": [ "mTOR" ], "type": "factoid", "id": "62507602e764a5320400000d", "snippets": [ { "offsetInBeginSection": 1065, "offsetInEndSection": 1116, "text": "a clinically relevant mTOR inhibitor, temsirolimus,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34565342", "endSection": "abstract" }, { "offsetInBeginSection": 258, "offsetInEndSection": 288, "text": "e mTOR-inhibitor temsirolimus ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34589671", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1314, "text": "mTOR inhibitors: 23 everolimus and 21 temsirolimus;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31331862", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 159, "text": "Temsirolimus is a mTOR inhibitor approved for the first-line treatment of advanced or metastatic renal cell carcinoma (a/mRCC) with poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34804848", "endSection": "abstract" } ] }, { "body": "Are circular RNAs implicated in diseases of the eye?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30444648", "http://www.ncbi.nlm.nih.gov/pubmed/33761053", "http://www.ncbi.nlm.nih.gov/pubmed/33074445", "http://www.ncbi.nlm.nih.gov/pubmed/29803556", "http://www.ncbi.nlm.nih.gov/pubmed/30428483", "http://www.ncbi.nlm.nih.gov/pubmed/33133146", "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "http://www.ncbi.nlm.nih.gov/pubmed/32914551", "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "http://www.ncbi.nlm.nih.gov/pubmed/30654635", "http://www.ncbi.nlm.nih.gov/pubmed/32844346", "http://www.ncbi.nlm.nih.gov/pubmed/30597308", "http://www.ncbi.nlm.nih.gov/pubmed/31295021" ], "ideal_answer": [ "Circular RNA (circRNA) are associated with several eye diseases." ], "exact_answer": "yes", "type": "yesno", "id": "6228b3553a8413c65300008b", "snippets": [ { "offsetInBeginSection": 442, "offsetInEndSection": 614, "text": "n this review, we summarized the function of circRNAs and indicated their roles in the pathogenesis of DR, which may provide new therapeutic targets for clinical treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33761053", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 182, "text": "This study aimed to determine whether circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for proliferative diabetic retinopathy (PDR).M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32914551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Discovery and validation of hsa_circ_0001953 as a potential biomarker for proliferative diabetic retinopathy in human blood.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32914551", "endSection": "title" }, { "offsetInBeginSection": 120, "offsetInEndSection": 210, "text": "Circular RNA hsa_circ_0000034 (circ_0000034) was reported to be upregulated in RB tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32844346", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1000, "text": "We recently identified a circular RNA transcript (circGRM4) that is significantly upregulated in the eye of cystathionine \u03b2-synthase-deficient mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33074445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Circular and long non-coding RNAs and their role in ophthalmologic diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30428483", "endSection": "title" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1343, "text": "In this review, we summarize current knowledge about gene expression regulators - long non-coding and circular RNA molecules in eye diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30428483", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1019, "text": "fied a circular RNA transcript (circGRM4) that is significantly upregulated in the eye of cystathionine \u03b2-synthase-deficient mice. We also discovered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33074445", "endSection": "abstract" }, { "offsetInBeginSection": 1044, "offsetInEndSection": 1216, "text": "NAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated. Progress in gene-cent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29803556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Circular RNA Expression Profiling Identifies Glaucoma-Related Circular RNAs in Various Chronic Ocular Hypertension Rat Models", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33133146", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Circular RNAs profiling in the cystathionine-\u03b2-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29803556", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Circular and long non-coding RNAs and their role in ophthalmologic diseases", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30428483", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Comprehensive circular RNA profiling of proliferative vitreoretinopathy and its clinical significance", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30597308", "endSection": "title" }, { "offsetInBeginSection": 635, "offsetInEndSection": 809, "text": " these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33133146", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Circular RNAs profiling in the cystathionine-\u03b2-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29803556", "endSection": "title" }, { "offsetInBeginSection": 424, "offsetInEndSection": 585, "text": "Although, increasing evidence suggests that circRNAs may also contribute in different ocular diseases, the outline of circRNAs in ocular diseases remains obscure", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "endSection": "abstract" }, { "offsetInBeginSection": 1202, "offsetInEndSection": 1342, "text": "In this review, we summarize current knowledge about gene expression regulators - long non-coding and circular RNA molecules in eye diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30428483", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 734, "text": "Recent studies recognized the vital roles that circRNAs played in the pathogenesis of various eye diseases, highlighting circRNAs as promising biomarkers for diagnosis and assessment of progression and prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 791, "text": "Partly because their circularity makes them resistant to degradation, they hold great promise as unique biomarkers for ocular and central nervous system (CNS) disorders", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30444648", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 999, "text": "In this review we consider the current state of knowledge regarding the potential role and underlying mechanism of circRNAs in ocular diseases including pterygium, age-related cataract, glaucoma, diabetic retinopathy, retinoblastoma, retinal vascular dysfunction and hyperhomocysteinemia induced ocular diseases, emphasizing that circRNAs could be promising biomarkers for the diagnosis and prognosis evaluation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 735, "text": "Recent studies recognized the vital roles that circRNAs played in the pathogenesis of various eye diseases, highlighting circRNAs as promising biomarkers for diagnosis and assessment of progression and prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 586, "text": "Although, increasing evidence suggests that circRNAs may also contribute in different ocular diseases, the outline of circRNAs in ocular diseases remains obscure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Circular RNAs: Novel Promising Biomarkers in Ocular Diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "endSection": "title" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1248, "text": "This review summarizes our current perception of the properties, biogenesis, and functions of circRNAs and the development of circRNA researches related to ophthalmologic diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, corneal neovascularization, cataract, pterygium, proliferative vitreoretinopathy, retinoblastoma, and ocular melanoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "CircRNA Is a Rising Star in Researches of Ocular Diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "endSection": "title" }, { "offsetInBeginSection": 736, "offsetInEndSection": 844, "text": "Interventions targeting circRNAs provide insights for developing novel treatments for these ocular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33015046", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1111, "text": "Future circRNAs-targeted intervention may become a novel therapeutic tool for the treatment of ocular diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31171902", "endSection": "abstract" }, { "offsetInBeginSection": 1623, "offsetInEndSection": 1754, "text": "Findings also revealed several microRNAs that are specific to each circRNA suggesting their roles in HHcy induced ocular disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29803556", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1001, "text": "Therefore, circRNAs may serve as potential regulators of corneal LG.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31295021", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 313, "text": "Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33133146", "endSection": "abstract" }, { "offsetInBeginSection": 1025, "offsetInEndSection": 1194, "text": "Although circular RNAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29803556", "endSection": "abstract" }, { "offsetInBeginSection": 1195, "offsetInEndSection": 1402, "text": "Progress in gene-centered analytics via improved microarray and bioinformatics are enabling dissection of genomic pathways however there is an acute under-representation of circular RNAs in ocular disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29803556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Circular RNAs constitute an inherent gene regulatory axis in the mammalian eye and brain 1.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30444648", "endSection": "title" }, { "offsetInBeginSection": 2149, "offsetInEndSection": 2429, "text": "Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33133146", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 707, "text": "Recent studies suggest that they are differentially expressed both in healthy ocular tissues as well as in eye pathologies, such as neovascularization, proliferative vitreoretinopathy, glaucoma, cataract, ocular malignancy or even strabismus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30428483", "endSection": "abstract" } ] }, { "body": "What happens to the expression levels of piRNAs in the case of intracranial aneurysm rupture?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32424559" ], "ideal_answer": [ "piRNAs showed a substantial decrease in RNA abundance that was sustained after IA rupture." ], "exact_answer": [ "Decreased" ], "type": "factoid", "id": "626aa929e764a53204000039", "snippets": [ { "offsetInBeginSection": 865, "offsetInEndSection": 1007, "text": "piRNAs and rRNAs showed a substantial decrease in RNA abundance that was sustained after IA rupture, whereas miRNAs were largely upregulated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32424559", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 450, "text": "We used next-generation sequencing to analyze the expression of sRNAs in patients in the acute phase of IA rupture (first 72 h), in the chronic phase (3-15 months), and controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32424559", "endSection": "abstract" } ] }, { "body": "Lucio\u2019s Phenomenon is characteristic to which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24863848", "http://www.ncbi.nlm.nih.gov/pubmed/34672479", "http://www.ncbi.nlm.nih.gov/pubmed/22475236", "http://www.ncbi.nlm.nih.gov/pubmed/31783808", "http://www.ncbi.nlm.nih.gov/pubmed/15985035", "http://www.ncbi.nlm.nih.gov/pubmed/19702985", "http://www.ncbi.nlm.nih.gov/pubmed/25509720", "http://www.ncbi.nlm.nih.gov/pubmed/22570037", "http://www.ncbi.nlm.nih.gov/pubmed/24346890", "http://www.ncbi.nlm.nih.gov/pubmed/19078473", "http://www.ncbi.nlm.nih.gov/pubmed/31114260", "http://www.ncbi.nlm.nih.gov/pubmed/17544965", "http://www.ncbi.nlm.nih.gov/pubmed/29048291", "http://www.ncbi.nlm.nih.gov/pubmed/17506277", "http://www.ncbi.nlm.nih.gov/pubmed/26566619" ], "ideal_answer": [ "Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy." ], "exact_answer": [ "leprosy" ], "type": "factoid", "id": "61f7c9ac882a024a10000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Diffuse multibacillary leprosy patient with Lucio's phenomenon and positive anticardiolipin antibody misdiagnosed as lupus erythematosus panniculitis in the People's Republic of China.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31114260", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Lucio's phenomenon (LP) is a special reactional state associated with diffuse multibacillary leprosy; both exhibit a limitative global distribution mainly in Mexico and Central America. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31114260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Diffuse Multibacillary Leprosy of Lucio and Latap\u00ed with Lucio's Phenomenon, Peru.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29048291", "endSection": "title" }, { "offsetInBeginSection": 148, "offsetInEndSection": 302, "text": "He also had Lucio's phenomenon, characterized by vascular thrombosis and invasion of blood vessel walls by leprosy bacilli, causing extensive skin ulcers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29048291", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 323, "text": "Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24863848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Lucio's phenomenon is defined as a variant of type 2 leprosy reaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22570037", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 326, "text": "Lucio's phenomenon is a rare manifestation among lepromatous patients with a rapid and severe evolution and high mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34672479", "endSection": "abstract" }, { "offsetInBeginSection": 213, "offsetInEndSection": 322, "text": "Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24863848", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 537, "text": " Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19078473", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Lucio's phenomenon (LP) is a special reactional state associated with diffuse multibacillary leprosy; both exhibit a limitative global distribution mainly in Mexico and Central America. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31114260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: Lucio's phenomenon is a rare manifestation of untreated leprosy which is seen almost exclusively in regions surrounding the Gul", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26566619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "O Lucio's phenomenon is an uncommon type 2 reactional state occurring exclusively in patients with diffuse lepromatous leprosy (Lucio-Latapi leprosy).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17506277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Lucio's phenomenon represents a serious cutaneous necrotizing reaction, which can occur with Lucio's leprosy and also in other forms of lepromatous leprosy. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24346890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "BACKGROUND: Lucio's phenomenon is a rare leprosy reaction characterised by bizarrely-shaped, purpuric skin lesions and ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22475236", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Lucio's phenomenon (LPh) is considered a necrotizing panvasculitis and a variant of leprosy Type 2 reaction, clinically characterised by necrotic-haemorrhagic lesions on the extremities and trunk. LP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25509720", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 306, "text": "estations. Ulcer is not a common feature in leprosy patients, except during reactional states, Lucio's phenomenon (LP), or secondary to neurop", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31783808", "endSection": "abstract" }, { "offsetInBeginSection": 688, "offsetInEndSection": 1019, "text": "to the clinical and histopathological manifestations, leprosy reactions may be separated in 2 or 3 different variants: reverse reaction (type I), erythema nodosum leprosum (type II), erythema polymorphous (type II) and Lucio's phenomenon, mainly considered a type II reaction, but sometimes designated type III. Type I leprosy reac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17544965", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 538, "text": "Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19078473", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 412, "text": "Lucio's phenomenon is characterized by necrotic ulcerations of the skin preferentially on the lower extremities usually in association with ongoing Lucio lepromatosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17506277", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Lucio's phenomenon/erythema necroticans is a peculiar reaction pattern that occurs in untreated pure primitive diffuse lepromatous leprosy (PPDL) and/or relapsing leprosy recognized as spotted leprosy of Lucio.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15985035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "BACKGROUND: Lucio's phenomenon is a rare and aggressive necrotising variant of erythema nodosum leprosum that classically occur in patients with undiagnosed, diffuse non-nodular lepromat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19702985", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1230, "text": "io's phenomenon was suspected. A clinical diagnosis of Lucio's phenomenon occurring in the backdrop of lepromatous leprosy was made.CONCLUSION: Though leprosy is still a prevalent disease, it has manifestations that are ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26566619", "endSection": "abstract" } ] }, { "body": "Where are the complexins expressed?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23658160", "http://www.ncbi.nlm.nih.gov/pubmed/30471689", "http://www.ncbi.nlm.nih.gov/pubmed/31691534", "http://www.ncbi.nlm.nih.gov/pubmed/23159779", "http://www.ncbi.nlm.nih.gov/pubmed/26019341" ], "ideal_answer": [ "Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane." ], "exact_answer": [ "presynaptic terminal" ], "type": "factoid", "id": "62507520e764a5320400000c", "snippets": [ { "offsetInBeginSection": 14, "offsetInEndSection": 283, "text": "Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31691534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Complexins (Cplxs) are small synaptic proteins that cooperate with SNARE-complexes in the control of synaptic vesicle (SV) fusion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26019341", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 231, "text": "Complexins are presynaptic proteins ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23658160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Complexins are small \u03b1-helical proteins that modulate neurotransmitter release by binding to SNARE complexes during synaptic vesicle exocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23159779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Complexins play a critical role in the regulation of neurotransmission by regulating SNARE-mediated exocytosis of synaptic vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30471689", "endSection": "abstract" } ] }, { "body": "Please list the tests used to diagnose Allergic Rhinitis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28502152", "http://www.ncbi.nlm.nih.gov/pubmed/11270471", "http://www.ncbi.nlm.nih.gov/pubmed/26298488", "http://www.ncbi.nlm.nih.gov/pubmed/12866316", "http://www.ncbi.nlm.nih.gov/pubmed/27279928", "http://www.ncbi.nlm.nih.gov/pubmed/30261765", "http://www.ncbi.nlm.nih.gov/pubmed/22888478", "http://www.ncbi.nlm.nih.gov/pubmed/9951327", "http://www.ncbi.nlm.nih.gov/pubmed/34031758", "http://www.ncbi.nlm.nih.gov/pubmed/25177851", "http://www.ncbi.nlm.nih.gov/pubmed/34476919", "http://www.ncbi.nlm.nih.gov/pubmed/17017490", "http://www.ncbi.nlm.nih.gov/pubmed/33598969", "http://www.ncbi.nlm.nih.gov/pubmed/2147615", "http://www.ncbi.nlm.nih.gov/pubmed/32597210", "http://www.ncbi.nlm.nih.gov/pubmed/14970151", "http://www.ncbi.nlm.nih.gov/pubmed/29682489", "http://www.ncbi.nlm.nih.gov/pubmed/33628036", "http://www.ncbi.nlm.nih.gov/pubmed/24053705", "http://www.ncbi.nlm.nih.gov/pubmed/287325", "http://www.ncbi.nlm.nih.gov/pubmed/34487076", "http://www.ncbi.nlm.nih.gov/pubmed/27127526", "http://www.ncbi.nlm.nih.gov/pubmed/9612876", "http://www.ncbi.nlm.nih.gov/pubmed/22384564" ], "ideal_answer": [ "Diagnosis of allergic rhinitis is made by a combination of medical history, physical examination, positive methacholine challenge result or bronchodilator responsiveness, determination of IgE-mediated sensitization, and specific inhalation challenge tests as the gold standard, specific IgE screening tests include Skin prick test (SPT), Phadiatop, and nasal provocation test (NPT)." ], "exact_answer": [ [ "positive methacholine challenge result or bronchodilator responsiveness" ], [ "determination of IgE-mediated sensitization" ], [ "Skin prick test (SPT)" ], [ "Phadiatop" ], [ "nasal provocation test (NPT)" ], [ "rhinomanometry" ] ], "type": "list", "id": "624f0813e764a5320400000a", "snippets": [ { "offsetInBeginSection": 809, "offsetInEndSection": 1101, "text": " Diagnosis of occupational respiratory allergy is made by a combination of medical history, physical examination, positive methacholine challenge result or bronchodilator responsiveness, determination of IgE-mediated sensitization, and specific inhalation challenge tests as the gold standard", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34031758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Skin Prick Test Versus Phadiatop as a Tool for Diagnosis of Allergic Rhinitis in Children.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32597210", "endSection": "title" }, { "offsetInBeginSection": 11, "offsetInEndSection": 297, "text": " Skin prick test (SPT) or Phadiatop, a multi-allergen IgE screening test, was used as a tool for detecting aeroallergen sensitization.OBJECTIVE: To compare SPT and Phadiatop as a tool for diagnosis allergic rhinitis (AR) using the nasal provocation test (NPT) as a comparative standard.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32597210", "endSection": "abstract" }, { "offsetInBeginSection": 20, "offsetInEndSection": 167, "text": "Skin prick test (SPT) with a wheal diameter of >3 mm, generally accepted as a positive, is most commonly use diagnostic tool for Allergic rhinitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34487076", "endSection": "abstract" }, { "offsetInBeginSection": 981, "offsetInEndSection": 1157, "text": "Considering that nasal obstruction is the most common symptom in patients with AR, the rhinomanometry (RM) test is the most indicated objective evaluation for nasal obstruction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34476919", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 354, "text": "Three allergic phenotypes of rhinitis have been described in adults: allergic rhinitis (AR), local allergic rhinitis (LAR), and dual allergic rhinitis (DAR, coexistence of AR and LAR). Nevertheless, most centers follow a diagnostic approach only based on skin prick test and serum allergen-specific IgE (collectively called atopy tests, AT). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33598969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Background: Screening for the existence of aeroallergens in patients with possible allergic rhinitis using venous blood samples has become more popular,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33628036", "endSection": "abstract" }, { "offsetInBeginSection": 234, "offsetInEndSection": 397, "text": "The aim of this study was to investigate the sensitivities and specificities of Phadiatop tests and total immunoglobulin E (IgE) levels in both adults and children", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33628036", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 544, "text": "However, AR patients can easily be diagnosed with skin prick test or allergen-specific IgE measurements in the serum, whereas NAR patients form a heterogeneous group and are difficult to diagnose because of an extensive list of different phenotypes, all varying in severity, underlying etiology and type of inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22888478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "OBJECTIVE: To study the pathogenesis of the patients with allergic rhinitis diagnosed by Skin Prick Test (SPT), especially about the epidemiologic data of the involved allergens.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22384564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Skin Prick Test Versus Phadiatop as a Tool for Diagnosis of Allergic Rhinitis in Children", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32597210", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Assessment of Nasal Immunoglobulin E Level in Atopic and Non-atopic Rhinitis Patients: A Tool for Diagnosis of Local Allergic Rhinitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28502152", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Local Allergic Rhinitis in Pediatric Patients: Is IgE Dosage in Nasal Lavage Fluid a Useful Diagnostic Method in Children?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29682489", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "After discussing the causes and immunopathology of allergic rhinitis, the authors describe the most frequently used diagnostic tests, confirming the validity of PRICK TEST, PRIST, RAST, and TNP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2147615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: Nasal provocation tests (NPTs) are indicated in confirming the diagnosis of allergic rhinitis if the clinical history, skin tests or sIgE are inconclusiv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24053705", "endSection": "abstract" }, { "offsetInBeginSection": 478, "offsetInEndSection": 645, "text": "This paper reviews the test characteristics of the history, skin tests, and in vitro tests in diagnosing allergic rhinitis from the perspective of decision thresholds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14970151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 936, "text": "OBJECTIVE: To identify the most useful combinations of symptoms and the results of radioallergosorbent tests (RASTs) and skin prick tests (SPTs) for the diagnosis of allergic rhinitis.DESIGN: A prospective comparison was made of symptoms and the results of RASTs and SPTs with 7 different nasal allergies; the references used were the \"consensus diagnoses\" provided by 3 experts.SETTING: Nineteen general practices in The Netherlands.PATIENTS: 365 consecutive patients aged 12 or over who visited their general practitioner because of chronic or recurrent nasal symptoms between 1 March 1990 and 1 March 1991.MAIN OUTCOME MEASURES: The most useful combinations of items from the history, RASTs, and SPTs, for the diagnosis of 7 different nasal allergies; the predictive probabilities of these combinations.RESULTS: Diagnostic criteria could be drawn up resulting in a near-perfect discrimination between patients diagnosed as having all", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9612876", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 312, "text": "Careful patient history, together with the skin prick test or RAST, usually allows an easy diagnosis of allergic rhinitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17017490", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 159, "text": "IgE). Nasal challenge is the gold standard for the diagnosis of allergic rhi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "[Diagnostic use of enzymatic RAST skin tests and determination of eosinophils in nasal mucosa in allergic rhinitis].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9951327", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 538, "text": "BACKGROUND: Allergic rhinitis is the most frequent allergic disease, characterized by nasal symptoms consisting of rhinorrhea, nasal block-age and sneezing triggered by and IgE mediated reaction to allergens.OBJECTIVE: To validate a questionnaire for the clinical diagnosis of allergic rhinitis.MATERIAL AND METHOD: A test of a test in which a questionnaire for the clinical diagnosis of allergic rhinitis was developed and validated it in 300 subjects (150 children, 150 adults, of both genders, 2-70 years), in allergy specialized cente", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25177851", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 412, "text": "skin testing, RAST, and nasal provocation tests, the last mentioned, as they are performed directly on the shock organ, have so far been found to give the most accurate picture of clinically dominant allergens and of the intensity and character of the rhinitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/287325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "A clinical decision support system for diagnosis of Allergic Rhinitis based on intradermal skin tests.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26298488", "endSection": "title" }, { "offsetInBeginSection": 1256, "offsetInEndSection": 1583, "text": "ity ranging from 60 to 100\u00a0%. The other two evaluated the accuracy of intradermal testing as a stand-alone test for diagnosing allergic rhinitis with sensitivity ranging from 60 to 79\u00a0% and specificity ranging from 68 to 69\u00a0%.CONCLUSIONS: Findings from this review suggest that skin-prick testing is accurate in discriminating ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27127526", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 264, "text": "Diagnostic allergy tests, such as skin tests and in vitro tests, can assist clinicians in determining whether nasal symptoms are allergic in origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14970151", "endSection": "abstract" }, { "offsetInBeginSection": 515, "offsetInEndSection": 780, "text": "gnosis of AR. Expert commentary: AR is traditionally diagnosed with the combined evaluation of history and allergen sensitization by in vivo skin prick tests and in vitro allergen specific IgE in serum, to confirm the correlation between clinical history and potent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261765", "endSection": "abstract" }, { "offsetInBeginSection": 456, "offsetInEndSection": 698, "text": "Tools that the allergist is more likely to use include nasal cytology, skin testing and in vitro assays for specific immunoglobulin E. Patients with pure nonallergic rhinitis have negative skin tests or clinically irrelevant positive results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12866316", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1415, "text": "It was concluded that the skin prick test can be used as a screening method for patients with allergic rhinitis, while the specific IgE detection can be used as an alternative for diagnosis of patients who are susceptible to the ID test or for those who are severely susceptible to allergic rhinitis such that medication can not be withdrawn for the ID test.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11270471", "endSection": "abstract" }, { "offsetInBeginSection": 1840, "offsetInEndSection": 2045, "text": "ity ranging from 60% to 100%. The other two studies evaluated the accuracy of intradermal testing as a stand-alone tool for diagnosing allergic rhinitis, with sensitivity ranging from 60% to 79% and specif", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27279928", "endSection": "abstract" } ] }, { "body": "Can epigenetic modifications be heritable?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32868918" ], "ideal_answer": [ "Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift." ], "exact_answer": "yes", "type": "yesno", "id": "626aaaa8e764a5320400003a", "snippets": [ { "offsetInBeginSection": 282, "offsetInEndSection": 462, "text": "Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32868918", "endSection": "abstract" } ] }, { "body": "What is the role of the AIMS65 score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33252414", "http://www.ncbi.nlm.nih.gov/pubmed/34497750", "http://www.ncbi.nlm.nih.gov/pubmed/32583220", "http://www.ncbi.nlm.nih.gov/pubmed/24587662", "http://www.ncbi.nlm.nih.gov/pubmed/23357496", "http://www.ncbi.nlm.nih.gov/pubmed/27740523", "http://www.ncbi.nlm.nih.gov/pubmed/26515955", "http://www.ncbi.nlm.nih.gov/pubmed/26668799", "http://www.ncbi.nlm.nih.gov/pubmed/26473120", "http://www.ncbi.nlm.nih.gov/pubmed/34550270", "http://www.ncbi.nlm.nih.gov/pubmed/31863515", "http://www.ncbi.nlm.nih.gov/pubmed/28839841", "http://www.ncbi.nlm.nih.gov/pubmed/26302496", "http://www.ncbi.nlm.nih.gov/pubmed/32668528", "http://www.ncbi.nlm.nih.gov/pubmed/25339841" ], "ideal_answer": [ "AIMS65 score is used to predict outcomes after upper GI bleeding." ], "type": "summary", "id": "62007f09c9dfcb9c0900001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Prospective Comparison of the AIMS65 Score, Glasgow-Blatchford Score, and Rockall Score for Predicting Clinical Outcomes in Patients with Variceal and Nonvariceal Upper Gastrointestinal Bleeding.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668528", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "BACKGROUND/AIMS: This study aimed to determine the performance of the AIMS65 score (AIMS65), Glasgow-Blatchford score (GBS), and Rockall score (RS) in predicting outcomes in patients with upper gastrointestinal bleeding (UGIB), and to compare the results between patients with nonvariceal UGIB (NVUGIB) and those with variceal UGIB (VUGIB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668528", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1443, "text": "CONCLUSION: AIMS65 is superior to GBS and RS in predicting mortality in patients with UGIB, and also precisely predicts the need for blood transfusion and the composite endpoint in patients with VUGIB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668528", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 402, "text": "Traditional scores like Glasgow-Blatchford score (GBS), Rockall score (RS), and AIMS65 score have been widely utilized in UGIB practice, however exhibiting limited practical use due to relative lack of user-friendly characters.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32583220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Comparison of AIMS65 and Glasgow Blatchford scores in predicting mortality in patients with upper gastrointestinal bleeding.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34550270", "endSection": "title" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1716, "text": "CONCLUSION: In this study, it was revealed that AIMS65, which is a score that can be easily calculated only with the data in the emergency department, outperformed Glasgow-Blatchford score in predicting mortality in patients with acute upper gastrointestinal bleeding who visited the emergency department.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34550270", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 386, "text": "We aimed to compare the performance of the ABC score (ABC), the AIMS65 score (AIMS65), the Glasgow-Blatchford score (GBS), and the pre-endoscopic Rockall score (pRS) in predicting 90-day mortality or rebleeding among patients with acute UGIB.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34497750", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1395, "text": "Conclusion: In patients with acute UGIB, ABC and pRS performed better than AIMS-65 and GBS in predicting 90-day mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34497750", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 181, "text": "The Rockall, Glasgow-Blatchford, and AIMS65 are useful and validated scoring systems for predicting the outcomes of patients with nonvariceal gastrointestinal bleeding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27740523", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 276, "text": "ointestinal tract. AIMS65 is an effective risk-scoring system to predict prognosis of upper gastrointestinal bleeding and can be easily calculated without ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33252414", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "The AIMS65 Score Is a Useful Predictor of Mortality in Patients with Nonvariceal Upper Gastrointestinal Bleeding: Urgent Endoscopy in Patients with High AIMS65 Scores.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26668799", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Is the AIMS65 score useful in predicting outcomes in peptic ulcer bleeding", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24587662", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "A Prospective, Multicenter Study of the AIMS65 Score Compared With the Glasgow-Blatchford Score in Predicting Upper Gastrointestinal Hemorrhage Outcomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26302496", "endSection": "title" }, { "offsetInBeginSection": 252, "offsetInEndSection": 423, "text": " We aimed to validate the AIMS65 score as a predictor of mortality in AVB, and to compare AIMS65 with established UGIB and liver disease severity risk stratification score", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31863515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "BACKGROUND/AIMS: To evaluate the ability of the recently proposed albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 years (AIMS65) score to predict mortality in patients with acute upper gastrointestinal bleeding (UGIB", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26473120", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 670, "text": "eds (ANVGIB). AIMS65 is a novel, recently derived scoring system, which has been proposed as an alternative to the more established Glasgow-Blatchford score (GBS).OBJECTIVE: To validate the AIMS65 scoring system in a predominantly Caucasian population from Scotland and compare it with the GBS.DESIGN: Retrospective study of patients presenting to a district general hospital in Scotland with a suspected diagnosis of ANVGIB who underwent inpatient upper GI endoscopy between March 2008 and March 2013.OUTCOMES: The pr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28839841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 478, "text": "BACKGROUND/AIMS: To evaluate the ability of the recently proposed albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 years (AIMS65) score to predict mortality in patients with acute upper gastrointestinal bleeding (UGIB).METHODS: AIMS65 scores were calculated in 251 consecutive patients presenting with acute UGIB by allotting 1 point each for albumin level <30 g/L, INR >1.5, alteration in mental status, systolic blood pressure \u226490", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26473120", "endSection": "abstract" }, { "offsetInBeginSection": 1698, "offsetInEndSection": 1970, "text": " in predicting the composite endpoint. GBS was superior to all other scores for predicting blood transfusion.CONCLUSION: The AIMS65 score is a simple risk stratification score for UGIB with accuracy superior to that of GBS and pre-endoscopy Rockall scores in predicting in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26515955", "endSection": "abstract" }, { "offsetInBeginSection": 1117, "offsetInEndSection": 1216, "text": " mean age was 65.2\u2005years and 30-day mortality 5.2%. AIMS65 was superior to the GBS in predicting mo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28839841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "A novel upper gastrointestinal bleeding risk stratification score (AIMS65) has recently been developed and validated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25339841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The AIMS65 score compared with the Glasgow-Blatchford score in predicting outcomes in upper GI bleeding.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357496", "endSection": "title" }, { "offsetInBeginSection": 726, "offsetInEndSection": 1054, "text": "f the 278 study patients, 6.5% died and 35% experienced the composite clinical endpoint. The AIMS65 score was superior in predicting inpatient mortality (AUROC, 0.93 vs 0.68; P < .001), whereas the GBRS was superior in predicting blood transfusions (AUROC, 0.85 vs 0.65; P < .01) The 2 scores were similar in predicting the comp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23357496", "endSection": "abstract" } ] }, { "body": "What is the gene ABCG1 encoding?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34608503", "http://www.ncbi.nlm.nih.gov/pubmed/32725886", "http://www.ncbi.nlm.nih.gov/pubmed/34461069" ], "ideal_answer": [ "ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues." ], "exact_answer": [ "ATP binding cassette (ABC) transporter" ], "type": "factoid", "id": "6252f496e764a53204000020", "snippets": [ { "offsetInBeginSection": 130, "offsetInEndSection": 189, "text": "ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32725886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34461069", "endSection": "abstract" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1034, "text": "ATP\u2011binding cassette sub\u2011family\u00a0G member\u00a01\u00a0(ABCG1) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34608503", "endSection": "abstract" } ] }, { "body": "Febrifugine could be repositioned for what diseases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24650700", "http://www.ncbi.nlm.nih.gov/pubmed/32518498", "http://www.ncbi.nlm.nih.gov/pubmed/31702585", "http://www.ncbi.nlm.nih.gov/pubmed/22327401", "http://www.ncbi.nlm.nih.gov/pubmed/27043972", "http://www.ncbi.nlm.nih.gov/pubmed/34628069", "http://www.ncbi.nlm.nih.gov/pubmed/26984239" ], "ideal_answer": [ "Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug.", "Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug. In addition, Prolyl-tRNA synthetase (PRS) drives protein translation in cells and are validated targets of febrifugine (FF) and its halogenated derivative halofuginone (HF). PRSs are of great interest for drug development against Plasmodium falciparum and Toxoplasma gondii. Febrifugine analogues have potential as Leishmania donovani trypanothione reductase inhibitors" ], "exact_answer": [ [ "schistosomiasis" ], [ "toxoplasmosis" ], [ "Visceral leishmaniasis" ], [ "toxoplasma gondii" ] ], "type": "list", "id": "6254340ae764a53204000028", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 251, "text": "Reports on the antischistosomal effect of several antimalarial drugs such as artesunate, mefloquine, and amodiaquine suggest that febrifugine, which exerts an antimalarial effect, can also be expected to possess antischistosomal potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32518498", "endSection": "abstract" }, { "offsetInBeginSection": 2122, "offsetInEndSection": 2259, "text": "Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32518498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 338, "text": "Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family that drives protein translation in cells. The apicomplexan PRSs are validated targets of febrifugine (FF) and its halogenated derivative halofuginone (HF). PRSs are of great interest for drug development against Plasmodium falciparum and Toxoplasma gondii. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31702585", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 1188, "text": "Two best ligands (FFG7 and FFG2) qualifying above screening parameters were further subjected to molecular dynamics simulation. Conducting these studies, here we confirmed that 6-chloro-3-[3-(3-hydroxy-2-piperidyl)-2-oxo-propyl]-7-(4-pyridyl) quinazolin-4-one can be potential drug candidate to fight against Leishmania donovani parasites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27043972", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "The trans-2,3-disubstituted piperidine, quinazolinone-containing natural product febrifugine (also known as dichroine B) and its synthetic analogue, halofuginone, possess antimalarial activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24650700", "endSection": "abstract" }, { "offsetInBeginSection": 87, "offsetInEndSection": 259, "text": "Febrifugine analogues are natural compound obtained from the traditional Chinese herbs have shown significant antimalarial and anticancerous efficacy in experimental model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26984239", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 259, "text": "inoma). Halofuginone (HL) is a less-toxic febrifugine derivative and has inhibitory effects on a variety of cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34628069", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 308, "text": "Febrifugine derivatives have been used to treat malaria, cancer, fibrosis and inflammatory disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22327401", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 309, "text": "Febrifugine derivatives have been used to treat malaria, cancer, fibrosis and inflammatory disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22327401", "endSection": "abstract" } ] }, { "body": "When was Volanesorsen approved in the EU?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31301033" ], "ideal_answer": [ "In May 2019, volanesorsen was approved in the EU for the treatment of adult patients with familial chylomicronemia syndrome." ], "exact_answer": [ "May 2019" ], "type": "factoid", "id": "626aeab6e764a5320400003e", "snippets": [ { "offsetInBeginSection": 313, "offsetInEndSection": 497, "text": "In May 2019, volanesorsen was approved in the EU for the treatment of adult patients with FCS based on positive results from the multinational, phase\u00a0III APPROACH and COMPASS studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31301033", "endSection": "abstract" } ] }, { "body": "Is Belimumab used for lupus nephritis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34560137", "http://www.ncbi.nlm.nih.gov/pubmed/30184477", "http://www.ncbi.nlm.nih.gov/pubmed/22584472", "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "http://www.ncbi.nlm.nih.gov/pubmed/33186226", "http://www.ncbi.nlm.nih.gov/pubmed/32002799", "http://www.ncbi.nlm.nih.gov/pubmed/34244988", "http://www.ncbi.nlm.nih.gov/pubmed/25005336", "http://www.ncbi.nlm.nih.gov/pubmed/29514612", "http://www.ncbi.nlm.nih.gov/pubmed/34521616", "http://www.ncbi.nlm.nih.gov/pubmed/34469086", "http://www.ncbi.nlm.nih.gov/pubmed/34600347" ], "ideal_answer": [ "Yes, Belimumab can be used for lupus nephritis." ], "exact_answer": "yes", "type": "yesno", "id": "61f7d2a5882a024a10000032", "snippets": [ { "offsetInBeginSection": 807, "offsetInEndSection": 1160, "text": "In particular, depletion (Obinutuzumab, anti-CD20 monoclonal antibody) or neutralization (Belimumab, anti-\"B-cell activating factor\" monoclonal antibody) of B lymphocytes, and the use of a calcineurin inhibitor with a low profile of renal and systemic toxicity (Voclosporin) demonstrated an improvement in renal response in addition to standard therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34469086", "endSection": "abstract" }, { "offsetInBeginSection": 745, "offsetInEndSection": 973, "text": "In this viewpoint, we discuss the pros and cons of voclosporin and belimumab as add-on agents to standard therapy, the first drugs to be licenced for lupus nephritis after recent successful randomised phase III clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34521616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34600347", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34560137", "endSection": "title" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1340, "text": "Thus, our data suggest that the addition of belimumab to standard therapy could attenuate the risk of lupus nephritis flare and eGFR decline in a broad spectrum of patients with lupus nephritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34560137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Belimumab and low-doses of mycophenolate mofetil as induction therapy of class IV lupus nephritis: case series and literature review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29514612", "endSection": "title" }, { "offsetInBeginSection": 177, "offsetInEndSection": 314, "text": "JECTIVE: To describe a patient whose active SLE (including lupus nephritis) was managed with the use of belimumab throughout pregnancy.ME", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25005336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 529, "text": "With vast implications through a novel mechanism, belimumab offers a new standard of treatment for physicians in the complications associated with SLE, specifically lupus nephritis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 658, "text": "CENT FINDINGS: Recently, the Belimumab in Subjects with Systemic Lupus Erythematosus - Lupus Nephritis trial tested belimumab, an inhibitor of B-cell activating factor, as an add-on therapy to steroids and either mycophenolate mofetil (MMF) or cyclophosphamide when given IV monthly over a period of 104 weeks at an effect size of 11% for a Primary Efficacy Renal Response. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33186226", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis. L", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 537, "text": "st implications through a novel mechanism, belimumab offers a new standard of treatment for physicians in the complications associated with SLE, specifically lupus nephritis. By targ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "endSection": "title" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1833, "text": "ic agents, rituximab may be used for refractory lupus nephritis patients in combination with another DMARD, and belimumab was recently approved by the US Food and Drug Administration for cSLE treatment in children aged > 5 years. New therapies targeting CD20, suc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34244988", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 633, "text": "s end, there is limited post-hoc randomized evidence to suggest beneficial effect of belimumab, administered on top of standard-of-care, during maintenance therapy in lupus nephritis. Type I ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30184477", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 902, "text": "e of recently approved belimumab in lupus nephritis eagerly awaits further documentation. Aggre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22584472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25969652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32002799", "endSection": "title" } ] }, { "body": "Is SOX10 expressed in melanoma cells?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33509946", "http://www.ncbi.nlm.nih.gov/pubmed/33002486", "http://www.ncbi.nlm.nih.gov/pubmed/34557039" ], "ideal_answer": [ "Yes,\nThe most commonly used melanocytic markers include S100, Melan-A, HMB45 and SOX10" ], "exact_answer": "yes", "type": "yesno", "id": "62507ca3e764a5320400000f", "snippets": [ { "offsetInBeginSection": 1225, "offsetInEndSection": 1397, "text": "Our study confirmed that SOX10 is an oncogene and activate Notch signaling pathway, which suggests the potential treatment for melanoma patients by target SOX10/Notch axis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34557039", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 433, "text": "The most commonly used melanocytic markers include S100, Melan-A, HMB45 and SOX10", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33509946", "endSection": "abstract" }, { "offsetInBeginSection": 1667, "offsetInEndSection": 1705, "text": "melanocytic markers melan-A and SOX10 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33002486", "endSection": "abstract" } ] }, { "body": "How many copies of LBX are found in teleosts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18541024" ], "ideal_answer": [ "In teleosts, that have undergone an additional genome duplication, 8 Lbx paralogons (three of which retain Lbx genes) were found.", "URL_0 > In teleosts, that have undergone an additional genome duplication, 8 LBx paralogons (three of which retain Lbx genes) were found." ], "exact_answer": [ "8" ], "type": "factoid", "id": "6253307fe764a53204000024", "snippets": [ { "offsetInBeginSection": 892, "offsetInEndSection": 1022, "text": "In teleosts, that have undergone an additional genome duplication, 8 Lbx paralogons (three of which retain Lbx genes) were found. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18541024", "endSection": "abstract" }, { "offsetInBeginSection": 894, "offsetInEndSection": 1023, "text": " teleosts, that have undergone an additional genome duplication, 8 Lbx paralogons (three of which retain Lbx genes) were found. P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18541024", "endSection": "abstract" }, { "offsetInBeginSection": 891, "offsetInEndSection": 1019, "text": " In teleosts, that have undergone an additional genome duplication, 8 Lbx paralogons (three of which retain Lbx genes) were foun", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18541024", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1000, "text": " genes) in amniotes. In teleosts, that have undergone an additional genome duplication, 8 Lbx paralogons (three of which retain L", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18541024", "endSection": "abstract" } ] }, { "body": "Which organizations approved Tagsedi in 2018?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32865784" ], "ideal_answer": [ "In 2018 Tagsedi was approved by the United States Food and Drug Agency, Health Canada, and European Commission." ], "exact_answer": [ [ "United States Food and Drug Agency" ], [ "Health Canada" ], [ "European Commission" ] ], "type": "list", "id": "626aecc6e764a53204000042", "snippets": [ { "offsetInBeginSection": 448, "offsetInEndSection": 720, "text": "A new drug named inotersen (brand name Tagsedi), also known as IONIS-TTRRX, has been approved by the United States Food and Drug Agency, Health Canada, and European Commission in 2018, and introduced to the market for patients in stage 1 and stage 2 hATTR polyneuropathy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32865784", "endSection": "abstract" } ] }, { "body": "What is the use of the CAHP score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33922191", "http://www.ncbi.nlm.nih.gov/pubmed/31987887", "http://www.ncbi.nlm.nih.gov/pubmed/32976962", "http://www.ncbi.nlm.nih.gov/pubmed/34302930", "http://www.ncbi.nlm.nih.gov/pubmed/30797049", "http://www.ncbi.nlm.nih.gov/pubmed/29555261", "http://www.ncbi.nlm.nih.gov/pubmed/26497161", "http://www.ncbi.nlm.nih.gov/pubmed/32330180", "http://www.ncbi.nlm.nih.gov/pubmed/34289964" ], "ideal_answer": [ "CAHP (cardiac arrest hospital prognosis) score is used to evaluate prognosis after cardiac arrest." ], "type": "summary", "id": "62007dcec9dfcb9c09000019", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "BACKGROUND: The novel simplified out-of-hospital cardiac arrest (sOHCA) and simplified cardiac arrest hospital prognosis (sCAHP) scores used for prognostication of hospitalised patients have not been externally validated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34289964", "endSection": "abstract" }, { "offsetInBeginSection": 1649, "offsetInEndSection": 1825, "text": "CONCLUSION: The performances of the original and simplified OHCA and CAHP scores in predicting neurological outcomes in successfully resuscitated OHCA patients were acceptable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34289964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "This study aimed to determine whether accuracy and sensitivity concerning neurological prognostic performance increased for survivors of out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM), using OHCA and cardiac arrest hospital prognosis (CAHP) scores and modified objective variables. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33922191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Performance of OHCA, NULL-PLEASE and CAHP scores to predict survival in Out-of-Hospital Cardiac Arrest due to acute coronary syndrome.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302930", "endSection": "title" }, { "offsetInBeginSection": 1139, "offsetInEndSection": 1301, "text": "CONCLUSION: The OHCA score, the NULL-PLEASE score and the CAHP score performed well in predicting in-hospital death in patients presenting OHCA secondary to ACS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34302930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Prognostic value of OHCA, C-GRApH and CAHP scores with initial neurologic examinations to predict neurologic outcomes in cardiac arrest patients treated with targeted temperature management.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32330180", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "AIM: We assessed the ability of the Out-of-Hospital Cardiac Arrest (OHCA) and the Cardiac Arrest Hospital Prognosis (CAHP) scores to predict neurological outcome following in-hospital cardiac arrest (IHCA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32976962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "AIM: The out-of-hospital cardiac arrest (OHCA) and cardiac arrest hospital prognosis (CAHP) scores were developed for early neuroprognostication after OHC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30797049", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 609, "text": " Baseline severity was assessed with Cardiac-Arrest-Hospital-Prognosis (CAHP) scor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29555261", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The CAHP (cardiac arrest hospital prognosis) score: A tool for risk stratification after out-of-hospital cardiac arrest in elderly patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31987887", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "OHCA (Out-of-Hospital Cardiac Arrest) and CAHP (Cardiac Arrest Hospital Prognosis) scores to predict outcome after in-hospital cardiac arrest: Insight from a multicentric registry.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32976962", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "This study aimed to determine whether accuracy and sensitivity concerning neurological prognostic performance increased for survivors of out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM), using OHCA and cardiac arrest hospital prognosis (CAHP) scores and modified objective variables", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33922191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after out-of-hospital cardiac arrest.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26497161", "endSection": "title" }, { "offsetInBeginSection": 156, "offsetInEndSection": 440, "text": "ging. This study aims to establish a stratification score for patients admitted in intensive care unit (ICU) after OHCA, according to their neurological outcome.METHODS AND RESULTS: The CAHP (Cardiac Arrest Hospital Prognosis) score was developed from the Sudden Death Expertise Cente", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26497161", "endSection": "abstract" } ] }, { "body": "What is the drug Aduhelm approved for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34657891", "http://www.ncbi.nlm.nih.gov/pubmed/34217830", "http://www.ncbi.nlm.nih.gov/pubmed/34324167", "http://www.ncbi.nlm.nih.gov/pubmed/34554982", "http://www.ncbi.nlm.nih.gov/pubmed/34585212" ], "ideal_answer": [ "he Food and Drug Administration (FDA) granted approval for Aduhelm (aducanumab) for the treatment of Alzheimer's disease under its accelerated approval program" ], "exact_answer": [ "treatment of Alzheimer's disease" ], "type": "factoid", "id": "6250787be764a5320400000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "According to the FDA, aducanumab (Aduhelm), the recently approved anti-Alzheimer drug, reduces the level of cerebral amyloid plaques-a hallmark finding in patients with Alzheimer's disease-and this will result in a reduction in clinical decline", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34657891", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "Aducanumab (aducanumab-avwa; Aduhelm\u2122) is a human, immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid \u03b2. It has been co-developed by Biogen and Eisai under license from Neurimmune for the treatment of Alzheimer's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34324167", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Aducanumab (Aduhelm), the first new drug to treat Alzheimer's", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34554982", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "On June 7th 2021, the Food and Drug Administration (FDA) granted approval for Aduhelm (aducanumab) for the treatment of Alzheimer's disease under its accelerated approval program", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34217830", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Aducanumab has been approved by the US Food and Drug Administration for treatment of Alzheimer's disease (AD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585212", "endSection": "abstract" } ] }, { "body": "What are the 4 histological types of lung cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6973391", "http://www.ncbi.nlm.nih.gov/pubmed/1656541", "http://www.ncbi.nlm.nih.gov/pubmed/25168588", "http://www.ncbi.nlm.nih.gov/pubmed/9063489", "http://www.ncbi.nlm.nih.gov/pubmed/10599212", "http://www.ncbi.nlm.nih.gov/pubmed/3019250", "http://www.ncbi.nlm.nih.gov/pubmed/8691638", "http://www.ncbi.nlm.nih.gov/pubmed/11765223", "http://www.ncbi.nlm.nih.gov/pubmed/2549305", "http://www.ncbi.nlm.nih.gov/pubmed/18299312", "http://www.ncbi.nlm.nih.gov/pubmed/30830374", "http://www.ncbi.nlm.nih.gov/pubmed/2038147", "http://www.ncbi.nlm.nih.gov/pubmed/12499060", "http://www.ncbi.nlm.nih.gov/pubmed/11269538", "http://www.ncbi.nlm.nih.gov/pubmed/1966930", "http://www.ncbi.nlm.nih.gov/pubmed/1663533", "http://www.ncbi.nlm.nih.gov/pubmed/18390646", "http://www.ncbi.nlm.nih.gov/pubmed/23754705", "http://www.ncbi.nlm.nih.gov/pubmed/33854137" ], "ideal_answer": [ "Lung cancer is broadly subclassified on the basis of histological features into squamous cell carcinoma, adenocarcinoma, large cell carcinoma and small cell carcinoma.", "There are 4 histological classes of lung cancer, small cell carcinoma and 3 non small cell lung cancer (NSCLC) types, adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma." ], "exact_answer": [ [ "small cell" ], [ "large cell" ], [ "adenocarcinoma" ], [ "squamous cell carcinoma" ] ], "type": "list", "id": "622ba6673a8413c653000098", "snippets": [ { "offsetInBeginSection": 265, "offsetInEndSection": 433, "text": "Lung cancer is broadly subclassified on the basis of histological features into squamous cell carcinoma, adenocarcinoma, large cell carcinoma and small cell carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12499060", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 319, "text": "According to histologic type, they were 129 adenocarcinomas, 56 squamous cell carcinomas, 4 small cell carcinomas, 8 large cell carcinomas, 8 adenosquamous cell carcinomas, 5 so-called carcinosarcomas and 2 other tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8691638", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 700, "text": "The commonest histological type found was squamous cell carcinoma in men and adenocarcinoma in women. Small cell carcinoma was uncommon. Squamous cell and large cell/undifferentiated type of carcinoma were significantly associated with smoking behaviour of the patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1966930", "endSection": "abstract" }, { "offsetInBeginSection": 686, "offsetInEndSection": 832, "text": "More non-smokers had adenocarcinoma than smokers (42% v 13%) and fewer had squamous cell carcinoma (32% v 49%) or small cell carcinoma (15% v 24%)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1656541", "endSection": "abstract" }, { "offsetInBeginSection": 506, "offsetInEndSection": 642, "text": "LTS: The most common histological types of lung cancer were squamous cell carcinoma (SQCC) in men and adenocarcinoma (ADC) in women. Dur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25168588", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 394, "text": "Lung cancer is mainly classified into 4 major histological types; squamous cell carcinoma, small cell carcinoma, adenocarcinoma and large cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3019250", "endSection": "abstract" }, { "offsetInBeginSection": 821, "offsetInEndSection": 926, "text": "These findings suggest that this antibody was useful for the histological differentiation of lung cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1663533", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1131, "text": "ypes of lung cancer were squamous cell carcinoma in 12, adenocarcinoma in 9, and small cell carcinoma in 4, and as to the disease stage, stages III to IV were predominant. Analysis on rela", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10599212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma. O", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754705", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 496, "text": " cell lines represented all four major histological types of human lung cancer including small cell carcinoma of the lung (SCCL) and the three types of non-SCCL (epidermoid, large cell, and adenocarcinoma). The SCC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6973391", "endSection": "abstract" }, { "offsetInBeginSection": 568, "offsetInEndSection": 812, "text": "ogical types of lung cancer were as follows, bronchioloalveolar cell carcinoma (39 cases), adenocarcinoma (36), squamous cell carcinoma (28), small cell lung cancer (27), large cell carcinoma (6), others (8), and unknown (10). There was a relat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11765223", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 653, "text": "ogical types of lung cancer were as follows: small cell lung cancer (n = 7), squamous cell carcinoma (n = 5), adenocarcinoma (n = 2), others (n = 5), and unknown (4). The onset of ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11269538", "endSection": "abstract" }, { "offsetInBeginSection": 1213, "offsetInEndSection": 1490, "text": "types of lung cancer, Thr495Pro SNP was significantly associated with small cell and squamous cell lung cancer, but not with adenocarcinoma, which suggested a potential interaction between this polymorphism and metabolic pathways related to smoking. The potential gene-environm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18299312", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hemat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33854137", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 393, "text": "Lung cancer is mainly classified into 4 major histological types; squamous cell carcinoma, small cell carcinoma, adenocarcinoma and large cell carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3019250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754705", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 240, "text": "Lung cancer is divided into 4 histological groups, such as small cell carcinoma, squamous cell carcinoma, adenocarcinoma and large cell carcinoma, representing different clinical behaviors", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9063489", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 479, "text": "The histological types were as follows: 8 adenocarcinoma, 4 large cell carcinoma, 1 squamous cell carcinoma, 1 small cell carcinoma, and 1 adenosquamous carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2038147", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23754705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "INTRODUCTION: Histologically lung cancer is classified into four major types: adenocarcinoma (Ad), squamous cell carcinoma (SqCC), large cell carcinoma (LCC), and small cell lung ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30830374", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 319, "text": "Histologic cell types of these lung cancer tissues included squamous-cell carcinoma (n = 30), adenocarcinoma (n = 28), large-cell carcinoma (n = 4), and small-cell carcinoma (n = 6).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2549305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 464, "text": "BACKGROUND: The magnitude of the link between cigarette smoking and lung cancer may vary by histological type.METHODS: We used polytomous logistic regression to evaluate whether aspects of smoking have different effects across four histological types in the Nurses' Health Study.RESULTS: From 1976 to 2002, we identified 1062 cases of lung cancer: squamous cell (n = 201), small cell (n = 236), adenocarcinoma (n = 543) and large cell carcinoma (n = 82), among 65 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18390646", "endSection": "abstract" }, { "offsetInBeginSection": 52, "offsetInEndSection": 241, "text": "Lung cancer is divided into 4 histological groups, such as small cell carcinoma, squamous cell carcinoma, adenocarcinoma and large cell carcinoma, representing different clinical behaviors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9063489", "endSection": "abstract" } ] }, { "body": "What is F105-P?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15908939" ], "ideal_answer": [ "F105-P is a protamine-antibody fusion protein designed to deliver siRNA to HIV-infected or envelope-transfected cells. In specific, it was designed with the protamine coding sequence linked to the C terminus of the heavy chain Fab fragment of an HIV-1 envelope antibody." ], "type": "summary", "id": "626233dbe764a53204000034", "snippets": [ { "offsetInBeginSection": 107, "offsetInEndSection": 382, "text": "We designed a protamine-antibody fusion protein to deliver siRNA to HIV-infected or envelope-transfected cells. The fusion protein (F105-P) was designed with the protamine coding sequence linked to the C terminus of the heavy chain Fab fragment of an HIV-1 envelope antibody.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15908939", "endSection": "abstract" } ] }, { "body": "Should edasalonexent be used for Duchenne muscular dystrophy patients?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34120912", "http://www.ncbi.nlm.nih.gov/pubmed/33678513" ], "ideal_answer": [ "No. In phase 3 clinical trial edasalonexent did not achieve statistical significance for improvement in primary and secondary functional endpoints for assessment of Duchenne muscular dystrophy. However, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of age." ], "type": "summary", "id": "61fa97d7c9dfcb9c09000006", "snippets": [ { "offsetInBeginSection": 945, "offsetInEndSection": 1378, "text": "Edasalonexent 100\u202fmg/kg was associated with slowing of disease progression and preservation of muscle function compared to an off-treatment control period, with decrease in levels of NF-\u03baB-regulated genes and improvements in biomarkers of muscle health and inflammation. These results support investigating edasalonexent in future trials and have informed the design of the edasalonexent phase 3 clinical trial in boys with Duchenne.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33678513", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1057, "text": "At week 52, differences between edasalonexent and placebo for NSAA total score and TFTs were not statistically significant, although there were consistently less functional declines in the edasalonexent group. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34120912", "endSection": "abstract" }, { "offsetInBeginSection": 1524, "offsetInEndSection": 1784, "text": "Although edasalonexent did not achieve statistical significance for improvement in primary and secondary functional endpoints for assessment of DMD, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34120912", "endSection": "abstract" }, { "offsetInBeginSection": 1523, "offsetInEndSection": 1782, "text": " Although edasalonexent did not achieve statistical significance for improvement in primary and secondary functional endpoints for assessment of DMD, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of ag", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34120912", "endSection": "abstract" } ] }, { "body": "What disease is presenilin involved in?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34593029", "http://www.ncbi.nlm.nih.gov/pubmed/34100423", "http://www.ncbi.nlm.nih.gov/pubmed/34662541", "http://www.ncbi.nlm.nih.gov/pubmed/31606858" ], "ideal_answer": [ "Loss-of-function mutations in PSEN1/2 genes are the leading cause of familial Alzheimer's disease (fAD)." ], "exact_answer": [ "familial Alzheimer's disease" ], "type": "factoid", "id": "624c838ee764a53204000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer's disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34100423", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 274, "text": "Loss-of-function mutations in PSEN1/2 genes are the leading cause of familial Alzheimer's disease (fAD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34662541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly. Few cases are familial (FAD), due to autosomal dominant mutations in presenilin-1 (PS1), presenilin-2 (PS2) or amyloid precursor protein (APP). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31606858", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "Mutations in the presenilin (PS/PSEN) genes encoding the catalytic components of \u03b3-secretase accelerate amyloid-\u03b2 (A\u03b2) and tau pathologies in familial Alzheimer's disease (AD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34593029", "endSection": "abstract" } ] }, { "body": "In what part of the body is the masseter muscle located?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28128087", "http://www.ncbi.nlm.nih.gov/pubmed/281140", "http://www.ncbi.nlm.nih.gov/pubmed/9257133", "http://www.ncbi.nlm.nih.gov/pubmed/19697646", "http://www.ncbi.nlm.nih.gov/pubmed/20553891", "http://www.ncbi.nlm.nih.gov/pubmed/10530166", "http://www.ncbi.nlm.nih.gov/pubmed/6465810", "http://www.ncbi.nlm.nih.gov/pubmed/27518245", "http://www.ncbi.nlm.nih.gov/pubmed/28194098", "http://www.ncbi.nlm.nih.gov/pubmed/33045182", "http://www.ncbi.nlm.nih.gov/pubmed/34474547", "http://www.ncbi.nlm.nih.gov/pubmed/31087731", "http://www.ncbi.nlm.nih.gov/pubmed/19625853", "http://www.ncbi.nlm.nih.gov/pubmed/6846512", "http://www.ncbi.nlm.nih.gov/pubmed/11688743", "http://www.ncbi.nlm.nih.gov/pubmed/34460885", "http://www.ncbi.nlm.nih.gov/pubmed/24864618", "http://www.ncbi.nlm.nih.gov/pubmed/19263353", "http://www.ncbi.nlm.nih.gov/pubmed/16965901" ], "ideal_answer": [ "In human anatomy, the masseter is one of the muscles of mastication and is located in the jaw." ], "exact_answer": [ "Jaw", "head", "face", "orofacial region", "mandible" ], "type": "factoid", "id": "62532ce6e764a53204000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Intramuscular hemangiomas of the masseter muscle are uncommon tumors and therefore can be difficult to accurately diagnose preoperatively, due to the unfamiliar presentation and deep location in the lateral face. A case of intramuscular hemangioma of the masseter muscle in a 66-yearold woman is presented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34474547", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 261, "text": "As part of this study, a comparative analysis of the temporal and masseter muscle electrical activity at rest and during mandible excursion positions (protrusion, laterotrusion and maximal occlusion) was performed among patients aged 21 to 68 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34460885", "endSection": "abstract" }, { "offsetInBeginSection": 8, "offsetInEndSection": 437, "text": " Masticatory myofascial trigger points (TrP) are one of the major causes of nondental pain in the orofacial region. Intramuscular injections are considered the first-line treatment for myofascial TrPs. The objectives of this study were to evaluate and compare the effectiveness of local anesthesia (LA), botulinum toxin (BTX), and platelet-rich plasma (PRP) injections for the treatment of myofascial TrPs in the masseter muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33045182", "endSection": "abstract" }, { "offsetInBeginSection": 121, "offsetInEndSection": 280, "text": "The organ extends from below the zygomatic bone line to the middle of the mandible body, between the skin and the masseter muscle, on both sides of the animal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31087731", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 548, "text": "The reported lesions were located in cheek masseter muscle, parotid gland, upper neck, upper gingiva and body of mandibular.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965901", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 235, "text": "The enormous strength of jaw closure is in large part due to the pinnated arrangement of the muscle fibres in the masseter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10530166", "endSection": "abstract" }, { "offsetInBeginSection": 431, "offsetInEndSection": 557, "text": "orted lesions were located in cheek masseter muscle, parotid gland, upper neck, upper gingiva and body of mandibular. The clin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16965901", "endSection": "abstract" }, { "offsetInBeginSection": 137, "offsetInEndSection": 289, "text": "e masseter muscle is the most frequent site and accounts for approximately 5% of all intramuscular vascular malformations in the head and neck region. M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24864618", "endSection": "abstract" }, { "offsetInBeginSection": 299, "offsetInEndSection": 486, "text": "e relationship between the masseter muscle and the mandible, including its ramal and body components, was chosen as the model for study in nineteen human fetuses (ages 16 to 36 weeks). Cr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/281140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Facial musculature is divided into masticatory muscles, i.e. M. masseter and M. buccalis, with bony insertions and smaller facial muscles involved in facial expression, which insert into bone and skin. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28128087", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 675, "text": "wo rigid bodies, the upper and lower jaws, including three dominant muscles, i.e. the masseter, the anterior portion of the temporalis and the lateral pterygoid. Static equilibrium", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9257133", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Benign hypertrophy of the masseter muscle is an uncommon entity important in the differential diagnosis of head and neck masses, particularly a unilateral mass located in the cheek", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6465810", "endSection": "abstract" }, { "offsetInBeginSection": 623, "offsetInEndSection": 974, "text": "First, jaw opening that was produced by mechanically pulling down the mandible evoked an optical response, which reflects neural excitation, in two cortical regions: the most rostroventral part of the primary somatosensory cortex (S1) and the border between the ventral part of the secondary somatosensory cortex (S2) and the insular oral region (IOR)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28194098", "endSection": "abstract" }, { "offsetInBeginSection": 1470, "offsetInEndSection": 1601, "text": "Masseter nerve stimulation initially excited the rostral part of the S2/IOR region, and an adjacent region responded to jaw opening", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28194098", "endSection": "abstract" }, { "offsetInBeginSection": 1603, "offsetInEndSection": 1848, "text": "The caudal part of the region showing the maximum response overlapped with the region responding to jaw opening, whereas the rostral part overlapped with the region responding to electrical stimulation of the maxillary and mandibular molar pulps", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28194098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The masseter muscle is an integral part of the oral facial complex and one of the muscles of mastication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19697646", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 190, "text": " 1% of cases. Masseter muscle localization is most common in head a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20553891", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 464, "text": "Among the head and neck muscles, masseter muscle is the most common location, with the rate of 4.9%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625853", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Benign hypertrophy of the masseter muscle is an uncommon entity important in the differential diagnosis of head and neck masses, particularly a unilateral mass located in the cheek.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6465810", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 755, "text": "ascular neoplasm Welsch and Hengerer, 1980 [4]. Of these 13.8% occur in the head and neck region, with the masseter muscle being the most common site, followed by the trapezi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27518245", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1502, "text": "It was concluded that: 1) radiopaque muscle markers are a valuable tool for analysis of muscle growth and alteration of muscle location; 2) the masseter muscle in the rhesus monkey undergoes elongation, probably due to addition of sarcomeres at the fiber-tendon junctions; and 3) posterior migration of the masseter muscle relative to the corpus of the mandible, probably due to the nature of its periosteal attachment, results in a stability of the anteroposterior position of the masseter muscle despite the anterior displacement of the mandible.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6846512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "AIM: The masseter muscle is often exploited by craniofacial surgeons in transposition operations to correct facial palsy, benign masseteric hypertrophy; or neurectomy-induced atrophy of the mu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19263353", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 736, "text": "The condition of a 36-year-old patient who applied to our clinic with the complaints of progressively increasing pain and progressively growing mass in the right cheek that appeared 1.5 years ago was diagnosed as arteriovenous malformation located in the masseter muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625853", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 889, "text": "In the cattle, goat, sheep and Sika deer, the rostral layer of the masseter muscle arises from the facial crest with its fleshy portion and is inserted into the tubercle on the mandible through the strong tendinous sheet.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11688743", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 362, "text": "Less than 1% of the vascular tumors are localized in a muscle, 15% of them are in the head and neck muscles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19625853", "endSection": "abstract" } ] }, { "body": "Which endothelial cell migration pathways were modulated at the gene expression level by rHDL-apoE3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34875308" ], "ideal_answer": [ "The most pronounced effect was observed for EC migration, with 42/198 genes being involved in the following EC migration-related pathways: 1) MEK/ERK, 2) PI3K/AKT/eNOS-MMP2/9, 3) RHO-GTPases, and 4) integrin." ], "exact_answer": [ [ "MEK/ERK" ], [ "PI3K/AKT/eNOS-MMP2/9" ], [ "RHO-GTPases" ], [ "integrin" ] ], "type": "list", "id": "6206b8c2c9dfcb9c0900003c", "snippets": [ { "offsetInBeginSection": 2037, "offsetInEndSection": 2241, "text": " The most pronounced effect was observed for EC migration, with 42/198 genes being involved in the following EC migration-related pathways: 1) MEK/ERK, 2) PI3K/AKT/eNOS-MMP2/9, 3) RHO-GTPases, 4) integrin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34875308", "endSection": "abstract" } ] }, { "body": "Is tivantinib effective for MET-high hepatocellular carcinoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29625879", "http://www.ncbi.nlm.nih.gov/pubmed/30190953", "http://www.ncbi.nlm.nih.gov/pubmed/32716114", "http://www.ncbi.nlm.nih.gov/pubmed/23167786" ], "ideal_answer": [ "No. In phase 3 clinical trials Tivantinib did not improve overall survival compared with placebo in patients with MET-high hepatocellular carcinoma despite promising phase 2 trial results." ], "exact_answer": "no", "type": "yesno", "id": "61f939a5882a024a1000004a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "BACKGROUND: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated with sorafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625879", "endSection": "abstract" }, { "offsetInBeginSection": 2694, "offsetInEndSection": 2870, "text": "INTERPRETATION: Tivantinib did not improve overall survival compared with placebo in patients with MET-high advanced hepatocellular carcinoma previously treated with sorafenib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625879", "endSection": "abstract" }, { "offsetInBeginSection": 1629, "offsetInEndSection": 1857, "text": "At a median follow-up of 18\u00b71 months (IQR 14\u00b71-23\u00b71), median overall survival was 8\u00b74 months (95% CI 6\u00b78-10\u00b70) in the tivantinib group and 9\u00b71 months (7\u00b73-10\u00b74) in the placebo group (hazard ratio 0\u00b797; 95% CI 0\u00b775-1\u00b725; p=0\u00b781).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625879", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 615, "text": "In Phase I and II studies, tivantinib (ARQ 197), an oral inhibitor of MET, demonstrated promising antitumor activity in patients with HCC, both as monotherapy and in combination with sorafenib. A randomized Phase II trial in second-line HCC showed improved overall survival (hazard ratio: 0.38; p = 0.01) in patients with MET-high tumors, as demonstrated by immunohistochemistry, treated with tivantinib versus placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30190953", "endSection": "abstract" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1856, "text": "This study did not confirm the significant efficacy of tivantinib as a second-line treatment for Japanese patients with MET-high hepatocellular carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32716114", "endSection": "abstract" }, { "offsetInBeginSection": 1155, "offsetInEndSection": 1572, "text": "Median progression-free survival was 2.8 (95% confidence interval: 2.7-2.9) and 2.3 (1.5-2.8) mo in the tivantinib and placebo groups, respectively (hazard ratio\u00a0=\u00a00.74, 95% confidence interval: 0.52-1.04, P\u00a0=\u00a0.082). Median overall survival was 10.3 (95% confidence interval: 8.1-11.6) and 8.5 (6.2-11.4) mo in the tivantinib and placebo group, respectively (hazard ratio\u00a0=\u00a00.82, 95% confidence interval: 0.58-1.15). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32716114", "endSection": "abstract" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1855, "text": "This study did not confirm the significant efficacy of tivantinib as a second-line treatment for Japanese patients with MET-high hepatocellular carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32716114", "endSection": "abstract" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1854, "text": "This study did not confirm the significant efficacy of tivantinib as a second-line treatment for Japanese patients with MET-high hepatocellular carcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32716114", "endSection": "abstract" }, { "offsetInBeginSection": 2694, "offsetInEndSection": 2868, "text": "INTERPRETATION: Tivantinib did not improve overall survival compared with placebo in patients with MET-high advanced hepatocellular carcinoma previously treated with sorafeni", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "BACKGROUND: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated wit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29625879", "endSection": "abstract" }, { "offsetInBeginSection": 866, "offsetInEndSection": 1066, "text": "ostic factor in HCC after sorafenib failure. Tivantinib demonstrated a nearly doubling of progression free and overall survival in the MET high group compared to placebo in a Phase II study in patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23167786", "endSection": "abstract" } ] }, { "body": "What is the function of the protein SLC26A5?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34294052", "http://www.ncbi.nlm.nih.gov/pubmed/33667636", "http://www.ncbi.nlm.nih.gov/pubmed/33951436", "http://www.ncbi.nlm.nih.gov/pubmed/34373481", "http://www.ncbi.nlm.nih.gov/pubmed/34695838" ], "ideal_answer": [ "SLC26A5 transporter prestin is fundamental for the higher hearing sensitivity and frequency selectivity of mammals. Prestin is a voltage-dependent transporter found in the cochlear outer hair cells responsible for their electromotility." ], "exact_answer": [ "voltage-dependent transporter" ], "type": "factoid", "id": "6251a2ffe764a5320400001c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "SLC26A5 transporter prestin is fundamental for the higher hearing sensitivity and frequency selectivity of mammals. Prestin is a voltage-dependent transporter found in the cochlear outer hair cells responsible for their electromotility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33667636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "The outer hair cell (OHC) membrane harbors a voltage-dependent protein, prestin (SLC26a5), in high density, whose charge movement is evidenced as a nonlinear capacitance (NLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34373481", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 127, "text": "Prestin (SLC26A5) is responsible for acute sensitivity and frequency selectivity in the vertebrate auditory system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34294052", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "The voltage-dependent motor protein prestin (also known as SLC26A5) is responsible for the electromotive behaviour of outer-hair cells and underlies the cochlear amplifier1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34695838", "endSection": "abstract" } ] }, { "body": "Is EuroQol 5-Dimension Health Assessment (EQ-5D) [a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease] a 5 question assessment?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24705224" ], "ideal_answer": [ "The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease.", "The EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease. It is a 6 question assessment." ], "exact_answer": "no", "type": "yesno", "id": "6250a545e764a53204000012", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 189, "text": "The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chron", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24705224", "endSection": "abstract" } ] }, { "body": "What are piRNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34337769" ], "ideal_answer": [ "PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi-piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs)." ], "type": "summary", "id": "626aa68ce764a53204000037", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi-piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34337769", "endSection": "abstract" } ] }, { "body": "Bimekizumab is used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34623614", "http://www.ncbi.nlm.nih.gov/pubmed/33727793", "http://www.ncbi.nlm.nih.gov/pubmed/34260044", "http://www.ncbi.nlm.nih.gov/pubmed/27859546", "http://www.ncbi.nlm.nih.gov/pubmed/34471992", "http://www.ncbi.nlm.nih.gov/pubmed/31214486", "http://www.ncbi.nlm.nih.gov/pubmed/34687214", "http://www.ncbi.nlm.nih.gov/pubmed/34077151", "http://www.ncbi.nlm.nih.gov/pubmed/30332893", "http://www.ncbi.nlm.nih.gov/pubmed/33549193", "http://www.ncbi.nlm.nih.gov/pubmed/34408825", "http://www.ncbi.nlm.nih.gov/pubmed/34178093", "http://www.ncbi.nlm.nih.gov/pubmed/33026212", "http://www.ncbi.nlm.nih.gov/pubmed/31172372", "http://www.ncbi.nlm.nih.gov/pubmed/34384327" ], "ideal_answer": [ "Bimekizumab is used for psoriasis." ], "exact_answer": [ "psoriasis" ], "type": "factoid", "id": "61f609d3882a024a10000024", "snippets": [ { "offsetInBeginSection": 339, "offsetInEndSection": 662, "text": "In BE RADIANT, patients were randomised 1:1 to bimekizumab 320\u00a0mg every 4\u00a0weeks (Q4W) or secukinumab 300\u00a0mg (weekly until Week 4, then Q4W). Three items (itching, skin pain and scaling) of the P-SIM were electronically assessed throughout the trial and were scored from 0 to 10 (none to very severe signs/symptoms/impacts).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34471992", "endSection": "abstract" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1444, "text": "CONCLUSIONS: In this review, we include a study of the new anti-IL-17 biological agents (secukinumab, ixekizumab, and bromalizumab) used for moderate-to-severe psoriasis and psoriatic arthritis treatment in clinical practice, as well as pivotal trials with bimekizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33026212", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Bimekizumab: the new drug in the biologics armamentarium for psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34178093", "endSection": "title" }, { "offsetInBeginSection": 231, "offsetInEndSection": 699, "text": "Due to its novel mechanism of action (dual inhibition of IL-17A and IL-17F), bimekizumab is considered a new therapeutic approach for the treatment of moderate-to-severe psoriasis. Bimekizumab has demonstrated superiority in all direct comparative clinical trials conducted, whether against ustekinumab (IL-12/23 inhibitor), adalimumab (TNF inhibitor) or secukinumab (IL-17A inhibitor), and has shown very encouraging results for the treatment of psoriatic arthritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34178093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 390, "text": "INTRODUCTION: Plaque psoriasis can significantly impact patients' quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients' experiences of signs, symptoms and impacts of psoriasis.METHODS: Pooled, blinded, 16-week data from 1002 patients in the BE\u00a0VIVID and BE\u00a0READY bimekizumab phase\u00a03 trials were analysed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34260044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Bimekizumab for the treatment of psoriatic disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30332893", "endSection": "title" }, { "offsetInBeginSection": 257, "offsetInEndSection": 437, "text": " of action (dual inhibition of IL-17A and IL-17F), bimekizumab is considered a new therapeutic approach for the treatment of moderate-to-severe psoriasis. Bimekizumab has demonstra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34178093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Bimekizumab: The First Dual Inhibitor of Interleukin (IL)-17A and IL-17F for the Treatment of Psoriatic Disease and Ankylosing Spondylitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31172372", "endSection": "title" }, { "offsetInBeginSection": 389, "offsetInEndSection": 505, "text": "Here we will discuss the safety and efficacy of bimekizumab in the treatment of moderate-to-severe plaque psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34077151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "An Overview of Bimekizumab for the Treatment of Psoriatic Arthritis: The Evidence so Far.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33727793", "endSection": "title" }, { "offsetInBeginSection": 1231, "offsetInEndSection": 1401, "text": "Long-term results and head-to-head trials comparing bimekizumab with other agents will be crucial to define the role of bimekizumab in the treatment of psoriatic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31172372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "BACKGROUND: Bimekizumab is a monoclonal antibody that selectively inhibits both IL-17A and IL-17F, currently under investigation for moderate to severe plaque psoriasis. Maintenance dosing every 4 weeks is", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34687214", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27859546", "endSection": "title" }, { "offsetInBeginSection": 588, "offsetInEndSection": 773, "text": "igen-binding site of bimekizumab neutralizes both IL-17A and IL-17F; phase I, II, and III studies have demonstrated its efficacy and safety in psoriasis and psoriatic arthritis. Sonelok", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34408825", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 495, "text": "de alone. Bimekizumab is the first human monoclonal antibody to exert simultaneous specific inhibition of IL-17A and IL-17\u00a0F, and has been studied in several phase II/III trials for psoriasi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34384327", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Bimekizumab: a dual IL-17A and IL-17F inhibitor for the treatment of psoriasis and psoriatic arthritis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34384327", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Bimekizumab for Moderate-to-Severe Plaque Psoriasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34077151", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Bimekizumab for the Treatment of Psoriasis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34623614", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33549193", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "Bimekizumab for the Treatment of Psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34623614", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Emerging treatment options for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis: evaluating bimekizumab and its therapeutic potential.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31214486", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 52, "text": "Bimekizumab for Moderate-to-Severe Plaque Psoriasis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34077151", "endSection": "title" }, { "offsetInBeginSection": 944, "offsetInEndSection": 1080, "text": "Bimekizumab is currently in clinical development for psoriasis, psoriatic arthritis, and ankylosing spondylitis, with promising results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31172372", "endSection": "abstract" }, { "offsetInBeginSection": 301, "offsetInEndSection": 537, "text": "ockade alone. Bimekizumab is the first human monoclonal antibody to exert simultaneous specific inhibition of IL-17A and IL-17\u00a0F, and has been studied in several phase II/III trials for psoriasis and PsA.AREAS COVERED: Bimekizumab is no", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34384327", "endSection": "abstract" } ] }, { "body": "What is the white mutation in Drosophila affecting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32964643", "http://www.ncbi.nlm.nih.gov/pubmed/29354028" ], "ideal_answer": [ "\u0392eyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance." ], "type": "summary", "id": "6252f0b7e764a5320400001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The classic eye-color gene white (w) in Drosophila melanogaster (fruitfly) has unexpected behavioral consequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32964643", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 798, "text": " We conclude that beyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29354028", "endSection": "abstract" } ] }, { "body": "Austrian syndrome is a rare entity characterized by Osler's triad. Please list the 3 components of Osler's triad.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14600140", "http://www.ncbi.nlm.nih.gov/pubmed/22030703", "http://www.ncbi.nlm.nih.gov/pubmed/18635383", "http://www.ncbi.nlm.nih.gov/pubmed/17599001", "http://www.ncbi.nlm.nih.gov/pubmed/30254807", "http://www.ncbi.nlm.nih.gov/pubmed/34710311", "http://www.ncbi.nlm.nih.gov/pubmed/32426357", "http://www.ncbi.nlm.nih.gov/pubmed/29848535", "http://www.ncbi.nlm.nih.gov/pubmed/31300377", "http://www.ncbi.nlm.nih.gov/pubmed/29967896", "http://www.ncbi.nlm.nih.gov/pubmed/31259104", "http://www.ncbi.nlm.nih.gov/pubmed/28266699", "http://www.ncbi.nlm.nih.gov/pubmed/31659532", "http://www.ncbi.nlm.nih.gov/pubmed/25218621", "http://www.ncbi.nlm.nih.gov/pubmed/19886075", "http://www.ncbi.nlm.nih.gov/pubmed/32923368", "http://www.ncbi.nlm.nih.gov/pubmed/30880376" ], "ideal_answer": [ "Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae", "Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae.", "Austrian syndrome is a rare triad of meningitis, pneumonia, and endocarditis caused by Streptococcus pneumoniae" ], "exact_answer": [ [ "pneumonia" ], [ "endocarditis" ], [ "meningitis" ] ], "type": "list", "id": "6250a917e764a53204000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Austrian syndrome is a rare triad of meningitis, pneumonia, and endocarditis caused by\u00a0Streptococcus pneumoniae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31259104", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 188, "text": "Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31659532", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 215, "text": "Known also as Osler's triad, Austrian syndrome is a complex pathology which consists of pneumonia, meningitis and endocarditis, all caused by the haematogenous dissemination of Streptococcus pneumoniae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Austrian syndrome is a very rare manifestation of invasive Streptococcus pneumoniae infection comprising a triad of pneumonia, meningitis, and endocarditis, also known as Osler's triad.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30254807", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 161, "text": "Osler's triad, which is the combination of endocarditis, pneumonia, and meningitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28266699", "endSection": "abstract" }, { "offsetInBeginSection": 126, "offsetInEndSection": 334, "text": "Osler's triad, which is the association of endocarditis, pneumonia, and meningitis caused by a single agent. This syndrome is called Austrian syndrome, when the infection is caused by Streptococcus pneumoniae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22030703", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Austrian syndrome or Osler's triad represents an association of pneumonia, meningitis and endocarditis caused by Streptococcus pneumonia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19886075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "We herein describe the case of a 65-year-old male patient who presented with Osler's triad, which is the combination of endocarditis, pneumonia, and meningitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28266699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Austrian syndrome is a rare triad of meningitis, pneumonia, and endocarditis caused by\u00a0Streptococcus pneumoniae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31259104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "BACKGROUND: Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae and carries drastic complications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31659532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Background: Known also as Osler's triad, Austrian syndrome is a complex pathology which consists of pneumonia, meningitis and endocarditis, all caused by the haematogenous dissemination of Streptococcus pneumoniae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "BACKGROUND: Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae and carries drastic compli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31659532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Austrian syndrome is a very rare manifestation of invasive Streptococcus pneumoniae infection comprising a triad of pneumonia, meningitis, and endocarditis, also known as Osler's triad. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30254807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Austrian syndrome is a rare triad of meningitis, pneumonia, and endocarditis caused by\u00a0Streptococcus pneumoniae.\u00a0", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31259104", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "Bi-valvular pneumococcal endocarditis in Austrian syndrome, which includes a triad of pneumococcal endocarditis, pneumonia, and meningitis, is a rare but life-threatening disease. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25218621", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Austrian syndrome is a rare triad of endocarditis, meningitis, and pneumonia caused by Streptococcus pneumonia described by Robert Austrian in 1956. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Austrian syndrome is a rare condition caused by invasive Streptococcus pneumoniae, comprising a triad of pneumococcal meningitis, endocarditis, and pneumonia. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31300377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The triad of pneumonia, meningitis, and endocarditis due to Streptococcus pneumoniae is known as Austrian syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17599001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Austrian's triad is a rare complication of disseminated Streptococcus pneumoniae infection consisting of pneumonia, meningitis, and endocarditis. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18635383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Background: Known also as Osler's triad, Austrian syndrome is a complex pathology which consists of pneumonia, meningitis and endocarditis, all caused by the haematogenous dissemination of Streptococcus pn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "This report describes two cases of Osler's triad of pneumonia, meningitis, and endocarditis, as a result of Streptococcus pneumoniae infection, also called Austrian's syndrome. In t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14600140", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "BACKGROUND: Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae and carries drastic complication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31659532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "Austrian syndrome is a rare medical condition characterised by the triad of pneumonia, meningitis and endocarditis due to Streptococcus pneumoniae Native aortic valve insufficiency is the most common cause of cardiac failure in these patients, requiring valve replacement", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29848535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Austrian syndrome is a very rare manifestation of invasive Streptococcus pneumoniae infection comprising a triad of pneumonia, meningitis, and endocarditis, also known as Osler's triad", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30254807", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The Austrian syndrome is a pathology caused by disseminated Streptococcus pneumoniae infection and characterized for the triad of pneumonia, endocarditis and meningitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30880376", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Austrian syndrome is a rare condition caused by invasive Streptococcus pneumoniae, comprising a triad of pneumococcal meningitis, endocarditis, and pneumonia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31300377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "We herein describe the case of a 65-year-old male patient who presented with Osler's triad, which is the combination of endocarditis, pneumonia, and meningitis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28266699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Austrian syndrome is a rare triad of endocarditis, meningitis, and pneumonia caused by Streptococcus pneumonia described by Robert Austrian in 1956", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Austrian syndrome is the clinical triad of endocarditis, meningitis, and pneumonia secondary to Streptococcus pneumoniae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34710311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Austrian syndrome consists of a triad of endocarditis, meningitis, and pneumonia caused by Streptococcus pneumoniae", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32426357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Austrian syndrome is a rare medical condition characterised by the triad of pneumonia, meningitis and endocarditis due to Streptococcus pneumoniae Native aortic valve insufficiency is the most common cause of cardiac failure in these patients, requiring valve replacement.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29848535", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 332, "text": "BACKGROUND: Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae and carries drastic complications.CASE PRESENTATION: A case of a 68-year-old female with a past medical history of hypertension and had a recen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31659532", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Austrian syndrome is a rare triad of endocarditis, meningitis, and pneumonia caused by Streptococcus pneumonia described by Robert Austrian in 1956.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923368", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Background: Known also as Osler's triad, Austrian syndrome is a complex pathology which consists of pneumonia, meningitis and endocarditis, all caused by the haematogenous dissemination of Streptococcus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Austrian syndrome or Osler's triad represents an association of pneumonia, meningitis and endocarditis caused by Streptococcus pneumonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19886075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Austrian syndrome is the clinical triad of endocarditis, meningitis, and pneumonia secondary to Streptococcus pneumoniae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34710311", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Austrian syndrome consists of a triad of endocarditis, meningitis, and pneumonia caused by Streptococcus pneumoniae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32426357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "This report describes two cases of Osler's triad of pneumonia, meningitis, and endocarditis, as a result of Streptococcus pneumoniae infection, also called Austrian's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14600140", "endSection": "abstract" } ] }, { "body": "What is the rate of epimutations in C. elegans?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32868918" ], "ideal_answer": [ "In C. elegans epimutations arise spontaneously at a rate approximately 25 times greater than DNA sequence changes." ], "exact_answer": [ "25 times greater than DNA sequence changes" ], "type": "factoid", "id": "626aab13e764a5320400003b", "snippets": [ { "offsetInBeginSection": 877, "offsetInEndSection": 1054, "text": "We show that epimutations arise spontaneously at a rate approximately 25 times greater than DNA sequence changes and typically have short half-lives of two to three generations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32868918", "endSection": "abstract" } ] }, { "body": "Is sacituzumab govitecan effective for breast cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34176192", "http://www.ncbi.nlm.nih.gov/pubmed/32529410", "http://www.ncbi.nlm.nih.gov/pubmed/33882206", "http://www.ncbi.nlm.nih.gov/pubmed/31584574", "http://www.ncbi.nlm.nih.gov/pubmed/34404686", "http://www.ncbi.nlm.nih.gov/pubmed/34761708", "http://www.ncbi.nlm.nih.gov/pubmed/26577300", "http://www.ncbi.nlm.nih.gov/pubmed/33187148", "http://www.ncbi.nlm.nih.gov/pubmed/34671504", "http://www.ncbi.nlm.nih.gov/pubmed/34651524", "http://www.ncbi.nlm.nih.gov/pubmed/31398063", "http://www.ncbi.nlm.nih.gov/pubmed/30507322", "http://www.ncbi.nlm.nih.gov/pubmed/30867160", "http://www.ncbi.nlm.nih.gov/pubmed/28291390", "http://www.ncbi.nlm.nih.gov/pubmed/34467774", "http://www.ncbi.nlm.nih.gov/pubmed/34688044", "http://www.ncbi.nlm.nih.gov/pubmed/33816696" ], "ideal_answer": [ "Yes. Sacituzumab Govitecan is a new and available treatment for metastatic triple-negative breast cancer." ], "exact_answer": "yes", "type": "yesno", "id": "61f608d4882a024a10000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Sacituzumab Govitecan (also known by the brand name TRODELVY\u00ae) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34467774", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy\u2122) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32529410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Results from a phase I/II trial suggest that an antibody-drug conjugate, sacituzumab govitecan, is active against refractory, metastatic triple-negative breast cancer. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30867160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "INTRODUCTION: Sacituzumab govitecan-hziy, approved in 2020 for treatment of metastatic triple-negative breast cancer, provides a new option for a population with a historically poor prognosis with standard ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34761708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Sacituzumab govitecan (SG), the first antibody-drug conjugate (ADC) approved for triple-negative breast cancer, incorporates the anti-TROP2 antibody hRS7 conjugated to a topoisomerase-1 (TOP1) inhibitor payload. We so", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34404686", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34671504", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "The ASCENT trial reports impressive results with a median overall survival (OS) increased from 6.7 months to 12.1 months with sacituzumab govitecan over single-agent chemotherapy, in metastatic triple negative breast cancer (TNBC) patients in second and subsequent line of therapy. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34688044", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "A phase II study indicates that sacituzumab govitecan (IMMU-132), a Trop-2-specific antibody linked to the irinotecan metabolite SN-38, prolongs the progression-free survival of patients with advanced triple-negative breast cancer. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26577300", "endSection": "abstract" }, { "offsetInBeginSection": 854, "offsetInEndSection": 1005, "text": "agents, sacituzumab govitecan, has been recently granted an accelerated approval for therapy of metastatic triple-negative breast cancer. In this artic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33187148", "endSection": "abstract" }, { "offsetInBeginSection": 250, "offsetInEndSection": 490, "text": "l 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32529410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34176192", "endSection": "title" }, { "offsetInBeginSection": 658, "offsetInEndSection": 895, "text": "ood and Drug Administration) recently approved the use of a Trop2-targeting ADC (antibody-drug conjugate), Sacituzumab Govitecan (IMMU-132), for metastatic, triple-negative breast cancer with at least two prior therapies. Here, we review", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33816696", "endSection": "abstract" }, { "offsetInBeginSection": 1021, "offsetInEndSection": 1141, "text": "sive disease. Sacituzumab govitecan represents an important advance in the treatment of mTNBC because of its efficacy an", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30507322", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 271, "text": "Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) that has shown promising efficacy in mTNBC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31584574", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1434, "text": "The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31398063", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 735, "text": "In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34176192", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291390", "endSection": "title" }, { "offsetInBeginSection": 826, "offsetInEndSection": 1049, "text": "Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31398063", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1277, "text": "Sacituzumab govitecan has shown promise in cancers outside of TNBC, such as urothelial and lung and is being evaluated in HR-positive breast cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34651524", "endSection": "abstract" }, { "offsetInBeginSection": 78, "offsetInEndSection": 634, "text": " prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.METHODS: In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-ne", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33882206", "endSection": "abstract" }, { "offsetInBeginSection": 857, "offsetInEndSection": 1004, "text": "Expert opinion Sacituzumab govitecan has promising survival benefits in patients with previously treated mTNBC based on data from the ASCENT trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34651524", "endSection": "abstract" }, { "offsetInBeginSection": 1586, "offsetInEndSection": 1730, "text": "Conclusion Sacituzumab govitecan was well tolerated and induced early and durable responses in heavily pretreated patients with metastatic TNBC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28291390", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33882206", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Sacituzumab Govitecan (also known by the brand name TRODELVY\u00ae) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34467774", "endSection": "abstract" } ] }, { "body": "What is Upadacitinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34551039", "http://www.ncbi.nlm.nih.gov/pubmed/32648334", "http://www.ncbi.nlm.nih.gov/pubmed/34464029" ], "ideal_answer": [ "Upadacitinib is an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA) and recently approved by the European Medicines Agency for the treatment of psoriatic arthritis (PsA)." ], "type": "summary", "id": "62513dc6e764a53204000014", "snippets": [ { "offsetInBeginSection": 65, "offsetInEndSection": 121, "text": "upadacitinib, an oral Janus kinase 1 selective inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648334", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 103, "text": "A number of Janus kinase (JAK) inhibitors (tofacitinib, filgotinib, upadacitinib) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34551039", "endSection": "abstract" } ] }, { "body": "Please list the difference between Pyoderma gangrenosum versus chronic venous ulceration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15778477", "http://www.ncbi.nlm.nih.gov/pubmed/17241569" ], "ideal_answer": [ "Even when other body sites are affected, pyoderma gangrenosum usually affects the upper and lower legs and feet or peristomal sites compared with chronic venous ulcers that are limited to the lower legs and feet. (2) Pyoderma gangrenosum can be associated with systemic diseases, especially inflammatory bowel disease. (4) Crater-like holes or cribriform scarring is commonly seen in pyoderma gangrenosum but not in chronic venous ulcers.", "Diagnosis of Pyoderma gangrenosum(PG) especially when trying to differentiate it from chronic venous ulceration(CVU) requires a number of clinical observations. 1. Pyoderma gangrenosum usually affects the upper and lower legs and feet or peristomal sites compared with chronic venous ulcers that are limited to the lower legs and feet. (2) Pyoderma gangrenosum can be associated with systemic diseases, especially inflammatory bowel disease. (3) Pustules and purulent discharge are features of pyoderma gangrenosum but not of chronic venous ulcers. (4) Crater-like holes or cribriform scarring is commonly seen in pyoderma gangrenosum but not in chronic venous ulcers. (5) Pathergy is a specific but not sensitive finding of pyoderma gangrenosum" ], "exact_answer": [ [ "PG affects the upper and lower legs and venous ilcers are limited to the the lower legs and feet" ], [ "PG is associated with systemic disease" ], [ "Pustules can occur with PG but not Chromic Vascular ulcers" ], [ "Cribriform scaring is seem with PG but not CVU" ], [ "Pathergy is seen in PG" ] ], "type": "list", "id": "6239ec36f0baec9a1b000001", "snippets": [ { "offsetInBeginSection": 526, "offsetInEndSection": 1148, "text": "Even when other body sites are affected, pyoderma gangrenosum usually affects the upper and lower legs and feet or peristomal sites compared with chronic venous ulcers that are limited to the lower legs and feet. (2) Pyoderma gangrenosum can be associated with systemic diseases, especially inflammatory bowel disease. (3) Pustules and purulent discharge are features of pyoderma gangrenosum but not of chronic venous ulcers. (4) Crater-like holes or cribriform scarring is commonly seen in pyoderma gangrenosum but not in chronic venous ulcers. (5) Pathergy is a specific but not sensitive finding of pyoderma gangrenosum", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241569", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Pyoderma gangrenosum is a skin disease characterized by wounds with blue-to-purple undermined borders surrounding purulent necrotic bases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15778477", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 744, "text": "S: (1) Even when other body sites are affected, pyoderma gangrenosum usually affects the upper and lower legs and feet or peristomal sites compared with chronic venous ulcers that are limited to the lower legs and feet. (2) P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241569", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 736, "text": "RESULTS: (1) Even when other body sites are affected, pyoderma gangrenosum usually affects the upper and lower legs and feet or peristomal sites compared with chronic venous ulcers that are limited to the lower legs and fee", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17241569", "endSection": "abstract" } ] }, { "body": "What is Mobilome-seq?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28212378", "http://www.ncbi.nlm.nih.gov/pubmed/33900594", "http://www.ncbi.nlm.nih.gov/pubmed/33900595" ], "ideal_answer": [ "Mobilome-seq is a method for selectively amplifying and sequencing eccDNAs. It relies on linear digestion of genomic DNA followed by rolling circle amplification of circular DNA. Both active DNA transposons and retrotransposons can be identified using this technique." ], "type": "summary", "id": "626aa780e764a53204000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Identification of Active Transposable Elements in Plants: The Mobilome-Seq Approach.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33900595", "endSection": "title" }, { "offsetInBeginSection": 347, "offsetInEndSection": 568, "text": "Here we applied a simple methodology based on the high throughput sequencing of extrachromosomal circular DNA (eccDNA) forms of active retrotransposons to characterize the repertoire of mobile retrotransposons in plants. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28212378", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 1001, "text": "When applying mobilome-seq to developmental stages in wild type rice, we identified PopRice as a highly active retrotransposon producing eccDNA forms in the wild type endosperm. The mobilome-seq strategy opens new routes for the characterization of a yet unexplored fraction of plant genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28212378", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 704, "text": "Mobilome-seq consists in selectively amplifying and sequencing eccDNAs. It relies on linear digestion of genomic DNA followed by rolling circle amplification of circular DNA. Both active DNA transposons and retrotransposons can be identified using this technique.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33900594", "endSection": "abstract" } ] }, { "body": "Which variables are included in the ALT-70 Score for cellulitis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28215446" ], "ideal_answer": [ "ALT-70 cellulitis score includes: Asymmetry (3 points), Leukocytosis (1 point), Tachycardia (1 point), and age \u226570 (2 points)." ], "exact_answer": [ [ "Asymmetry" ], [ "Leukocytosis" ], [ "Tachycardia" ], [ "age \u226570" ] ], "type": "list", "id": "62008130c9dfcb9c0900001c", "snippets": [ { "offsetInBeginSection": 997, "offsetInEndSection": 1189, "text": "We converted these variables into a points system to create the ALT-70 cellulitis score as follows: Asymmetry (3 points), Leukocytosis (1 point), Tachycardia (1 point), and age \u226570 (2 points).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28215446", "endSection": "abstract" } ] }, { "body": "List biomarkers for sepsis.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34517744", "http://www.ncbi.nlm.nih.gov/pubmed/34551574", "http://www.ncbi.nlm.nih.gov/pubmed/32705879", "http://www.ncbi.nlm.nih.gov/pubmed/34634653", "http://www.ncbi.nlm.nih.gov/pubmed/33140076", "http://www.ncbi.nlm.nih.gov/pubmed/31537145", "http://www.ncbi.nlm.nih.gov/pubmed/34524647", "http://www.ncbi.nlm.nih.gov/pubmed/33274532" ], "ideal_answer": [ "HCK, PRKCD, SIRPA, DOK3, ITGAM, LTB4R, MAPK14, MALT1, NLRC3, LCK\nC-Reactive Protein (CRP), Procalcitonin (PCT) and Interleukin 6 (IL-6)\nsTM" ], "exact_answer": [ [ "CRP" ], [ "PCT" ], [ "IL-6" ], [ "HCK" ], [ "PRKCD" ], [ "SIRPA" ], [ "DOK3" ], [ "ITGAM" ], [ "LTB4R" ], [ "MAPK14" ], [ "MALT1" ], [ "NLRC3" ], [ "LCK" ], [ "sTM" ] ], "type": "list", "id": "625ba1fae764a5320400002d", "snippets": [ { "offsetInBeginSection": 1378, "offsetInEndSection": 1569, "text": "NLRP3 is useful for the early identification of high-risk septic patients, particularly septic shock patients. Moreover, elevated NRLP3 levels could result in poor septic prediction outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34634653", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 980, "text": "the expression of CD45RO on T lymphocytes is the only useful biomarker for diagnosis of neonatal late-onset sepsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31537145", "endSection": "abstract" }, { "offsetInBeginSection": 1675, "offsetInEndSection": 1743, "text": "These results suggest that sepsis severity leads to CoQ10 depletion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32705879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Procalcitonin (PCT) is useful for differentiating between viral and bacterial infections and for reducing the unnecessary use of antibiotics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34517744", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1653, "text": "These data provide new evidence on the usefulness of plasma procalcitonin as a reliable diagnostic biomarker in the diagnostic algorithm of peripheral blood culture contamination among patients hospitalized in tertiary care.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34524647", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 347, "text": "Soluble thrombomodulin (sTM), tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin-antithrombin complex (TAT) and \u03b12-plasmin inhibitor-plasmin complex (PIC) are biomarkers of endothelium injury and coagulation dysfunction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34551574", "endSection": "abstract" }, { "offsetInBeginSection": 1506, "offsetInEndSection": 1613, "text": "sTM was considered as a sensitive biomarker for the early prediction of septic shock and sepsis-induced DIC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34551574", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1418, "text": "The selected hub gene of pediatric sepsis was combined with the markers of cell surface and found 10 core genes (HCK, PRKCD, SIRPA, DOK3, ITGAM, LTB4R, MAPK14, MALT1, NLRC3, LCK). ROC showed that AUC of the 10 core genes for diagnosis of pediatric sepsis was above 0.9.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33274532", "endSection": "abstract" }, { "offsetInBeginSection": 1250, "offsetInEndSection": 1439, "text": "The CEA POC reader was demonstrated for immunoassay of C-Reactive Protein (CRP), Procalcitonin (PCT) and Interleukin 6 (IL-6), towards a three biomarker panel to aid the diagnosis of sepsis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33140076", "endSection": "abstract" } ] }, { "body": "Is Acute Necrotizing Encephalopathy (ANE) which typically affects young, healthy children usually triggered by exposure to air pollution?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15032389", "http://www.ncbi.nlm.nih.gov/pubmed/20020117", "http://www.ncbi.nlm.nih.gov/pubmed/33318805", "http://www.ncbi.nlm.nih.gov/pubmed/19643689", "http://www.ncbi.nlm.nih.gov/pubmed/19811512", "http://www.ncbi.nlm.nih.gov/pubmed/24029031", "http://www.ncbi.nlm.nih.gov/pubmed/32861530", "http://www.ncbi.nlm.nih.gov/pubmed/33904484", "http://www.ncbi.nlm.nih.gov/pubmed/24665298", "http://www.ncbi.nlm.nih.gov/pubmed/34405641", "http://www.ncbi.nlm.nih.gov/pubmed/25873770", "http://www.ncbi.nlm.nih.gov/pubmed/33761695", "http://www.ncbi.nlm.nih.gov/pubmed/32256627", "http://www.ncbi.nlm.nih.gov/pubmed/25973284", "http://www.ncbi.nlm.nih.gov/pubmed/31304037" ], "ideal_answer": [ "Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children. Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection", "Acute Necrotizing Encephalopathy (ANE) usually occurs in children under 4 years old after a viral infection", "Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection" ], "exact_answer": "no", "type": "yesno", "id": "622905043a8413c65300008e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children. ANE is characterized by a preceding viral illness followed by seizures and rapid progressive neurologic deterioration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32861530", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 124, "text": "Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33761695", "endSection": "abstract" }, { "offsetInBeginSection": 2256, "offsetInEndSection": 2330, "text": "ANE usually occurs in children under 4 years old after influenza infection", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34405641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Acute necrotizing encephalopathy of childhood (ANEC) is a disease, characterized by a respiratory or gastrointestinal infection, accompanied with fever, rapid alteration of consciousness, and seizures.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32256627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 230, "text": "Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25873770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Acute necrotizing encephalopathy (ANE) typically affects young, healthy children who develop rapid-onset severe encephalopathy triggered by viral infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Recurrent acute necrotizing encephalopathy following influenza A in a genetically predisposed family.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811512", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Background: Among the influenza-associated encephalopathies, acute necrotizing encephalopathy (ANE) has a particularly poor prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33318805", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 280, "text": "Since it was first recognized, neurological complications including acute necrotizing encephalopathy (ANE) have been globally documented in association with this viral infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24029031", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Background: Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy seen commonly in children triggered by various prodromal viral infections, most common being influenza virus and Human herpe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33904484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Background: Acute necrotizing encephalopathy (ANE), known as influenza-associated encephalitis, typically affects", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31304037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Acute necrotizing encephalopathy (ANE) is a rapidly progressing neurologic disorder that occurs in children after common viral infections of the respiratory or gastrointestinal systems. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25973284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Acute necrotizing encephalopathy (ANE) typically affects young, healthy children who develop rapid-onset severe encephalopathy triggered by viral infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19811512", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 223, "text": "Background: Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy seen commonly in children triggered by various prodromal viral infections, most common being influenza virus and Human herpes virus-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33904484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Acute necrotizing encephalopathy (ANE) presents in children after common viral infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19643689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "Acute necrotizing encephalopathy of childhood (ANEC) is a disease characterized by respiratory or gastrointestinal infection and high fever accompanying with rapid alteration of consciousness and seizures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24665298", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 385, "text": "Background: Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy seen commonly in children triggered by various prodromal viral infections, most common being influenza virus and Human herpes virus-6.Objective: We report two rare cases of ANE preceded by Chikungunya infection.Cases: A 13-year old girl presented with a three-day history of headache, fever, se", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33904484", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Acute necrotizing encephalopathy (ANE) is a rapidly progressing neurologic disorder that occurs in children after common viral infections of the respiratory or gastrointestinal systems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25973284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Acute necrotizing encephalopathy (ANE) presents in children after common viral infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19643689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Acute necrotizing encephalopathy of childhood associated with influenza type B virus infection in a 3-year-old girl.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15032389", "endSection": "title" }, { "offsetInBeginSection": 473, "offsetInEndSection": 705, "text": "We report a 12-year-old girl infected with influenza A H1N1 whose clinical course was complicated by rapid progressive neurologic deterioration and striking CT and MRI findings consistent with acute necrotizing encephalopathy (ANE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20020117", "endSection": "abstract" }, { "offsetInBeginSection": 766, "offsetInEndSection": 970, "text": "We report a 3-year-old previously healthy girl presenting with acute necrotizing encephalopathy of childhood associated with influenza type B virus infection, which resulted in severe neurologic sequelae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15032389", "endSection": "abstract" } ] }, { "body": "What is Waylivra?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31301033" ], "ideal_answer": [ "Volanesorsen (Waylivra\u00ae), an antisense oligonucleotide inhibitor of apolipoprotein CIII (apoCIII) mRNA to treat familial chylomicronemia syndrome (FCS), hypertriglyceridemia and familial partial lipodystrophy (FPL)." ], "type": "summary", "id": "626aea6ae764a5320400003d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Volanesorsen (Waylivra\u00ae), an antisense oligonucleotide inhibitor of apolipoprotein CIII (apoCIII) mRNA, is being developed by Ionis Pharmaceuticals through its subsidiary company, Akcea Therapeutics, to treat familial chylomicronemia syndrome (FCS), hypertriglyceridemia and familial partial lipodystrophy (FPL). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31301033", "endSection": "abstract" } ] }, { "body": "Which disease can be prevented with PfSPZ Vaccine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32920641", "http://www.ncbi.nlm.nih.gov/pubmed/28216244", "http://www.ncbi.nlm.nih.gov/pubmed/26324116", "http://www.ncbi.nlm.nih.gov/pubmed/33947856", "http://www.ncbi.nlm.nih.gov/pubmed/28362549", "http://www.ncbi.nlm.nih.gov/pubmed/29438525", "http://www.ncbi.nlm.nih.gov/pubmed/28199305", "http://www.ncbi.nlm.nih.gov/pubmed/28097230", "http://www.ncbi.nlm.nih.gov/pubmed/33205741", "http://www.ncbi.nlm.nih.gov/pubmed/32444192", "http://www.ncbi.nlm.nih.gov/pubmed/25917675", "http://www.ncbi.nlm.nih.gov/pubmed/29187199", "http://www.ncbi.nlm.nih.gov/pubmed/34518679", "http://www.ncbi.nlm.nih.gov/pubmed/28223498", "http://www.ncbi.nlm.nih.gov/pubmed/33674699", "http://www.ncbi.nlm.nih.gov/pubmed/29554084", "http://www.ncbi.nlm.nih.gov/pubmed/29943719", "http://www.ncbi.nlm.nih.gov/pubmed/27158907", "http://www.ncbi.nlm.nih.gov/pubmed/26590432" ], "ideal_answer": [ "PfSPZ Vaccine is used for prevention of malaria." ], "exact_answer": [ "malaria" ], "type": "factoid", "id": "61f7d745882a024a10000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "BACKGROUND: A live-attenuated Plasmodium falciparum sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (same P. falciparum strain as in the vaccine).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32920641", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1663, "text": "CONCLUSIONS: Administering 4 stacked priming injections (multi-dose priming) resulted in 40% VE against heterologous CHMI, while dose escalation of PfSPZ using single-dose priming was not significantly protective. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32920641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 374, "text": "Plasmodium falciparum sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33205741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-na\u00efve adults. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34518679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to asses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28097230", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1791, "text": "In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26324116", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1791, "text": "In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26590432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 333, "text": "A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28223498", "endSection": "abstract" }, { "offsetInBeginSection": 225, "offsetInEndSection": 417, "text": "Here, we aimed to investigate if P. falciparum sporozoite binding and invasion-inhibitory IgM antibodies are induced following immunization of malaria-preexposed volunteers with PfSPZ Vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29438525", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554084", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 432, "text": " of the candidate human malaria vaccines, which is based on human malaria sporozoites and called PfSPZ Vaccine, has been shown to protect a significant proportion of vaccine recipients from getting malaria. PfS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28362549", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "BACKGROUND: A live-attenuated Plasmodium falciparum sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (sa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32920641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We asse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27158907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "BACKGROUND: Plasmodium falciparum sporozite (PfSPZ) Vaccine is a metabolically active, non-replicating, whole malaria sporozoite vaccine that has been reported to be safe and protective against P falciparum controlled human malaria infection in malaria-naive ind", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28216244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Sterile protection against human malaria by chemoattenuated PfSPZ vaccine", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28199305", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against malaria. A cri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32444192", "endSection": "abstract" }, { "offsetInBeginSection": 230, "offsetInEndSection": 379, "text": "nfections. The radiation attenuated sporozoite (PfSPZ) vaccine has been considered the gold standard for malaria vaccines because of its unparalleled", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29187199", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 267, "text": "CKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses admin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28097230", "endSection": "abstract" }, { "offsetInBeginSection": 1370, "offsetInEndSection": 1543, "text": " have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28097230", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1017, "text": "otective efficacy has been demonstrated in a small number of volunteers after intravenous (IV) inoculation of radiation-attenuated PfSPZ or in those who were exposed to live PfSPZ while on malaria chemoprophylaxis. These advance", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25917675", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 609, "text": "pared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33674699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33947856", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Protection against malaria at 1 year and immune correlates following PfSPZ vaccination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27158907", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28223498", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 66, "text": "Protection against Plasmodium falciparum malaria by PfSPZ Vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28097230", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28199305", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34518679", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 270, "text": "We are using controlled human malaria infection (CHMI) by direct venous inoculation (DVI) of cryopreserved, infectious Plasmodium falciparum (Pf) sporozoites (SPZ) (PfSPZ Challenge) to try to reduce time and costs of developing PfSPZ Vaccine to prevent malaria in Africa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29943719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27158907", "endSection": "abstract" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1542, "text": "CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28097230", "endSection": "abstract" }, { "offsetInBeginSection": 1100, "offsetInEndSection": 1294, "text": "Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27158907", "endSection": "abstract" }, { "offsetInBeginSection": 1434, "offsetInEndSection": 1570, "text": "Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28223498", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28223498", "endSection": "abstract" }, { "offsetInBeginSection": 3181, "offsetInEndSection": 3380, "text": "ON: PfSPZ Vaccine was well tolerated and safe. PfSPZ Vaccine showed significant protection in African adults against P falciparum infection throughout an entire malaria season.FUNDING: US National In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28216244", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28097230", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "BACKGROUND: Plasmodium falciparum sporozite (PfSPZ) Vaccine is a metabolically active, non-replicating, whole malaria sporozoite vaccine that has been reported to be safe and protective against P falciparum controlled human malaria infection in malaria-naive ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28216244", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 875, "text": "We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28199305", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1124, "text": "Three doses of 5.12\u2009\u00d7\u2009104 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28199305", "endSection": "abstract" } ] }, { "body": "Is Phospholemman a membrane protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31840988", "http://www.ncbi.nlm.nih.gov/pubmed/26429909", "http://www.ncbi.nlm.nih.gov/pubmed/23246925" ], "ideal_answer": [ "Yes, FXYD1 (encoding phospholemman) is a transmembrane protein." ], "exact_answer": "yes", "type": "yesno", "id": "6251465ae764a53204000017", "snippets": [ { "offsetInBeginSection": 772, "offsetInEndSection": 824, "text": " the transmembrane lipoprotein phospholemman (FXYD1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31840988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Phospholemman (FXYD1) is a single-transmembrane protein regulator of Na,K-ATPase, expressed strongly in heart, skeletal muscle, and brain and phosphorylated by protein kinases A and C at Ser-68 and Ser-63, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26429909", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 347, "text": "We previously identified FXYD1 (encoding phospholemman; a protein containing the motif phenylalanine-X-tyrosine-aspartate), a gene encoding a transmembrane modulator of the Na, K-ATPase (NKA) enzyme,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23246925", "endSection": "abstract" } ] }, { "body": "What is MACE in the context of cardiotoxicity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34396256", "http://www.ncbi.nlm.nih.gov/pubmed/32493217", "http://www.ncbi.nlm.nih.gov/pubmed/19589442", "http://www.ncbi.nlm.nih.gov/pubmed/28544100", "http://www.ncbi.nlm.nih.gov/pubmed/25075166", "http://www.ncbi.nlm.nih.gov/pubmed/32947416", "http://www.ncbi.nlm.nih.gov/pubmed/34533592", "http://www.ncbi.nlm.nih.gov/pubmed/27451136", "http://www.ncbi.nlm.nih.gov/pubmed/33766256", "http://www.ncbi.nlm.nih.gov/pubmed/33966333", "http://www.ncbi.nlm.nih.gov/pubmed/30626381", "http://www.ncbi.nlm.nih.gov/pubmed/25212799", "http://www.ncbi.nlm.nih.gov/pubmed/26071994", "http://www.ncbi.nlm.nih.gov/pubmed/34075158", "http://www.ncbi.nlm.nih.gov/pubmed/34396181", "http://www.ncbi.nlm.nih.gov/pubmed/31399624", "http://www.ncbi.nlm.nih.gov/pubmed/12076217" ], "ideal_answer": [ "MACE is an acronym for Major Adverse Cardiovascular Events.", "major adverse cardiac events (MACE)" ], "exact_answer": [ "Major Adverse Cardiovascular Events." ], "type": "factoid", "id": "624d9492e764a53204000006", "snippets": [ { "offsetInBeginSection": 400, "offsetInEndSection": 442, "text": "major adverse cardiovascular events (MACE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33966333", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 611, "text": "major cardiac adverse events (MACEs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34533592", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 275, "text": "major adverse cardiac events (MACE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32947416", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 687, "text": "Major adverse cardiovascular events (MACE)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33766256", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1276, "text": "endpoint is defined as the occurrence of a major adverse cardiac event (MACE). The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32493217", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Objectives: The purpose of this study was to evaluate whether immune checkpoint inhibitors (ICIs) are associated with an\u00a0increased risk of major adverse cardiovascular events (MACE) compared with non-ICI therapies in patients with lung\u00a0cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34396181", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "BACKGROUND: Main adverse cardiac events (MACE) are essentially composite endpoints for assessing safety and efficacy of treatment processes of acute coronary syndrome (ACS) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30626381", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 247, "text": "Major adverse cardiac events (MACE) are common after renal transplant, especially in the perioperative period, leading to excess morbidity and mortality. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25075166", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 286, "text": "aim of this study was to explore the predictive value of soluble osteoclast-associated receptor (sOSCAR) level for the major adverse cardiovascular events (MACE) occurring within 30\u00a0days after ACS. From J", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34075158", "endSection": "abstract" }, { "offsetInBeginSection": 482, "offsetInEndSection": 699, "text": "ciated with the occurrence of MACE, defined as a composite of cardiac death, congestive heart failure, and myocardial re-infarction (adjusted hazard ratio: 3.74; 95% confidence interval: 2.21 to 6.34). IS%LV \u226525% was ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25212799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "The study aimed to determine whether high sensitivity C-reactive protein to prealbumin (hs-CRP/PAB) ratio could be used to predict in-hospital major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31399624", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 489, "text": "Objectives: The purpose of this study was to characterize major adverse cardiac events (MACE) in ICI-treated lung cancer patients based in a rural setting and to assess the utility of C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) in the diagnosis of iR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34396256", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 397, "text": "OBJECTIVE: To evaluate whether LUTS severity can be considered as a significant risk factor of major adverse cardiac events (MACE) in the male populatio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27451136", "endSection": "abstract" }, { "offsetInBeginSection": 2568, "offsetInEndSection": 2761, "text": "PATIENT SUMMARY: We evaluated whether the severity of lower urinary tract symptoms could be considered as a significant risk factor for major adverse cardiac events (MACE) in the male populatio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27451136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "CONTEXT: Percutaneous coronary intervention (PCI) is associated with excellent short-term improvements in ischemic symptoms, yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events (MACE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12076217", "endSection": "abstract" }, { "offsetInBeginSection": 687, "offsetInEndSection": 996, "text": "SES, n = 508; and PES, n = 576). Major adverse cardiac events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, or target vessel revascularization (TVR).RESULTS: The patients treated with EES were older, presented more frequently with acute myocardial infarction, and had more ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19589442", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 706, "text": "Therefore, the objectives of the present study were twofold: (1) to characterize the occurrence of and risk factors for major adverse cardiac events (MACEs: symptomatic heart failure and cardiac death) in a large contemporaneous population of adult patients treated with anthracyclines and (2) to test the value of LVEF and LV dimensions obtained using echocardiography in the prediction of MACE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26071994", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 674, "text": " 7, 30, and 90 days. Secondary outcomes included major adverse cardiac events (MACE; all-cause mortality, AMI, and revascularization) and the indivi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28544100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Objectives: The purpose of this study was to evaluate whether immune checkpoint inhibitors (ICIs) are associated with an\u00a0increased risk of major adverse cardiovascular events (MACE) compared with non-ICI therapies in patients with lung\u00a0cancer.Background: ICIs activate the host immune system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34396181", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 625, "text": "n be fatal. There have been few reports of iRC from a rural cancer population and few data for iRC and inflammatory biomarkers.Objectives: The purpose of this study was to characterize major adverse cardiac events (MACE) in ICI-treated lung cancer patients based in a rural setting and to assess the utility of C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) in the diagnosis of iRC.Methods: Patients with lung cancer treated with ICIs at Vidant Medical Center/East Carolina University (VMC/ECU) between 2015 and 2018", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34396256", "endSection": "abstract" } ] }, { "body": "Which clinical trials led to the first approval of Volanesorsen by the EU?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31301033" ], "ideal_answer": [ "The approval of Volanesorsen by the EU was based on the positive results from the multinational, phase III APPROACH and COMPASS studies." ], "exact_answer": [ "APPROACH and COMPASS" ], "type": "factoid", "id": "626aeb2fe764a5320400003f", "snippets": [ { "offsetInBeginSection": 313, "offsetInEndSection": 496, "text": "In May 2019, volanesorsen was approved in the EU for the treatment of adult patients with FCS based on positive results from the multinational, phase\u00a0III APPROACH and COMPASS studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31301033", "endSection": "abstract" } ] }, { "body": "Can Isradipine slow progression of Early Parkinson Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32227247", "http://www.ncbi.nlm.nih.gov/pubmed/34766657", "http://www.ncbi.nlm.nih.gov/pubmed/33460320", "http://www.ncbi.nlm.nih.gov/pubmed/33716705" ], "ideal_answer": [ "No. In a multicenter, randomized, parallel-group, double-blind, placebo-controlled trial Isradipine did not slow progression of Early Parkinson Disease." ], "exact_answer": "no", "type": "yesno", "id": "61f93c38882a024a1000004b", "snippets": [ { "offsetInBeginSection": 1255, "offsetInEndSection": 1569, "text": "Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P\u00a0= 0.85).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227247", "endSection": "abstract" }, { "offsetInBeginSection": 1924, "offsetInEndSection": 2046, "text": "Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227247", "endSection": "abstract" }, { "offsetInBeginSection": 1511, "offsetInEndSection": 1727, "text": "ONS: These results are consistent with the recent secondary analysis of the STEADY-PD III clinical trial-suggesting that clinically attainable brain exposure to isradipine may slow early-stage PD progression. \u00a9 2021 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34766657", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 404, "text": "These findings suggest that greater exposure to isradipine might slow disease progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34766657", "endSection": "abstract" }, { "offsetInBeginSection": 1942, "offsetInEndSection": 2064, "text": "erm treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.Primary Funding So", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227247", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 304, "text": "BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end of t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34766657", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1233, "text": "RESULTS: Isradipine exposures did not correlate with the primary clinical outcome, changes in the antiparkinson therapy-adjusted Unified Parkinson's Disease Rating Scale parts I-III score over 36\u00a0months (Spearman rank correlation coefficient, rs : ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33460320", "endSection": "abstract" }, { "offsetInBeginSection": 313, "offsetInEndSection": 402, "text": " These findings suggest that greater exposure to isradipine might slow disease progressio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34766657", "endSection": "abstract" }, { "offsetInBeginSection": 1924, "offsetInEndSection": 2044, "text": "Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32227247", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1160, "text": "However, in a recently completed phase 3 clinical trial, the dihydropyridine (DHP) LTCC inhibitor isradipine failed to slow disease progression in early PD patients, questioning the feasibility of DHPs for PD therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33716705", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34766657", "endSection": "abstract" } ] }, { "body": "Is neurofilament light marker for disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34375485", "http://www.ncbi.nlm.nih.gov/pubmed/32255388", "http://www.ncbi.nlm.nih.gov/pubmed/31961243", "http://www.ncbi.nlm.nih.gov/pubmed/34602928", "http://www.ncbi.nlm.nih.gov/pubmed/32306372" ], "ideal_answer": [ "Yes,\nSerum neurofilament light chain (sNfL) is a marker of neuroaxonal injury leading to numerous diseases such as frontotemporal dementia (FTD) and Multiple sclerosis (MS)." ], "exact_answer": "yes", "type": "yesno", "id": "625144c9e764a53204000016", "snippets": [ { "offsetInBeginSection": 1452, "offsetInEndSection": 1624, "text": "sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32255388", "endSection": "abstract" }, { "offsetInBeginSection": 24, "offsetInEndSection": 323, "text": "Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34375485", "endSection": "abstract" }, { "offsetInBeginSection": 941, "offsetInEndSection": 1131, "text": "Neurofilament light chain has a potential role in differentiating patients with frontotemporal dementia from healthy controls, patients with Alzheimer's dementia, and psychiatric disorders. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306372", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 85, "text": " Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31961243", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1433, "text": "sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31961243", "endSection": "abstract" }, { "offsetInBeginSection": 769, "offsetInEndSection": 863, "text": "Neurofilament light chain (NfL) is a relatively new biomarker for MS diagnosis and follow up. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34602928", "endSection": "abstract" } ] }, { "body": "Is resistance training usually associated with increasing muscle hypertrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/14766764", "http://www.ncbi.nlm.nih.gov/pubmed/31254797", "http://www.ncbi.nlm.nih.gov/pubmed/8681927", "http://www.ncbi.nlm.nih.gov/pubmed/8792025", "http://www.ncbi.nlm.nih.gov/pubmed/32740889", "http://www.ncbi.nlm.nih.gov/pubmed/25911469", "http://www.ncbi.nlm.nih.gov/pubmed/3057312", "http://www.ncbi.nlm.nih.gov/pubmed/18796867", "http://www.ncbi.nlm.nih.gov/pubmed/31009427", "http://www.ncbi.nlm.nih.gov/pubmed/28315193", "http://www.ncbi.nlm.nih.gov/pubmed/11173673", "http://www.ncbi.nlm.nih.gov/pubmed/21445603", "http://www.ncbi.nlm.nih.gov/pubmed/31482093", "http://www.ncbi.nlm.nih.gov/pubmed/34052876", "http://www.ncbi.nlm.nih.gov/pubmed/17166396", "http://www.ncbi.nlm.nih.gov/pubmed/24188499", "http://www.ncbi.nlm.nih.gov/pubmed/1864770", "http://www.ncbi.nlm.nih.gov/pubmed/28663372", "http://www.ncbi.nlm.nih.gov/pubmed/28346813", "http://www.ncbi.nlm.nih.gov/pubmed/28280974", "http://www.ncbi.nlm.nih.gov/pubmed/10932036", "http://www.ncbi.nlm.nih.gov/pubmed/12392444", "http://www.ncbi.nlm.nih.gov/pubmed/31161403", "http://www.ncbi.nlm.nih.gov/pubmed/29608833", "http://www.ncbi.nlm.nih.gov/pubmed/24751198", "http://www.ncbi.nlm.nih.gov/pubmed/32162291", "http://www.ncbi.nlm.nih.gov/pubmed/8153497", "http://www.ncbi.nlm.nih.gov/pubmed/31268995", "http://www.ncbi.nlm.nih.gov/pubmed/19196907", "http://www.ncbi.nlm.nih.gov/pubmed/20560706" ], "ideal_answer": [ "Traditional resistance exercises have been widely used to promote muscle strength and hypertrophy.", "Is resistance training usually associated with increasing muscle hypertrophy? Yes.", "While traditional resistance exercises have been widely used to promote muscle strength and hypertrophy in the elderly" ], "exact_answer": "yes", "type": "yesno", "id": "62532d42e764a53204000022", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 132, "text": "While traditional resistance exercises have been widely used to promote muscle strength and hypertrophy in the elderly, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31254797", "endSection": "abstract" }, { "offsetInBeginSection": 1520, "offsetInEndSection": 1824, "text": " These findings suggest that in young untrained men, progressing from a training frequency of once per week to a training frequency of 5 times per week with equated volume produces similar gains in LBM and muscle strength as a constant training frequency of once per week, over an 8-week training period.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009427", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 184, "text": "Resistance training is one of the effective methods to overcome a decline in muscle mass,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29608833", "endSection": "abstract" }, { "offsetInBeginSection": 1673, "offsetInEndSection": 1788, "text": "Therefore, in RT prescription for elbow flexors hypertrophy, single-joint exercises such as BC should be emphasized", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31268995", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1620, "text": "Our studies establish that resistance training in older adults with type 2 diabetes results in muscle fiber hypertrophy, despite a greater accumulation of inflammatory cytokine transcripts in muscle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17166396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Resistance training results in muscle hypertrophy and improves glycemic control in patients with type 2 diabetes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17166396", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Resistance training (RT) is a popular method of conditioning to enhance sport performance as well as an effective form of exercise to attenuate the age-mediated decline in muscle strength and mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12392444", "endSection": "abstract" }, { "offsetInBeginSection": 849, "offsetInEndSection": 985, "text": "Enzyme activities, reflecting oxidative potential; decrease during long-term heavy resistance training, resulting in muscle hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3057312", "endSection": "abstract" }, { "offsetInBeginSection": 1034, "offsetInEndSection": 1277, "text": "Optimal adaptations to resistance training (muscle hypertrophy and strength increases) also seem to occur in the late afternoon, which is interesting, since cortisol and, particularly, testosterone (T) concentrations are higher in the morning.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Heavy resistance training is associated with increased body weight, lean body mass, and muscle cross-sectional area.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3057312", "endSection": "abstract" }, { "offsetInBeginSection": 2682, "offsetInEndSection": 2945, "text": "The implications for this are (a) athletes are advised to coincide training times with performance times, and (b) individuals may experience greater hypertrophy and strength gains when resistance training protocols are designed dependent on individual T response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20560706", "endSection": "abstract" }, { "offsetInBeginSection": 1128, "offsetInEndSection": 1262, "text": "Therefore, the combination of resistance training and overexpression of IGF-I induced greater hypertrophy than either treatment alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14766764", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 396, "text": "The intake of protein after resistance training increases plasma amino acids, which results in the activation of signaling molecules leading to increased muscle protein synthesis (MPS) and muscle hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24751198", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 447, "text": "The rate and amount of muscle hypertrophy associated with resistance training is influenced by a wide array of variables including the training program, plus training experience, gender, genetic predisposition, and nutritional status of the individual.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31482093", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Resistance training is commonly prescribed to enhance strength/power qualities and is achieved via improved neuromuscular recruitment, fiber type transition, and/ or skeletal muscle hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31482093", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 285, "text": "The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28280974", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "It has been proposed that protein supplementation during resistance exercise training enhances muscle hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346813", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND: Effects of resistance training on muscle strength and hypertrophy are well established in adults and younger elderly.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32740889", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Chronic resistance training induces increases in muscle fibre cross-sectional area (CSA), otherwise known as hypertrophy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10932036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28663372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "In resistance training, it has been empirically accepted that muscle hypertrophy is developed by low intensity and high volume training, while muscle strength and power are developed by high intensity and low volume training. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8681927", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 355, "text": "gh intensity resistance training (HIRT) has led to increased protein synthesis, along with muscle hypertrophy measured at the whole body, whole muscle, and muscle fibre levels, in older adults. Typica", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11173673", "endSection": "abstract" }, { "offsetInBeginSection": 111, "offsetInEndSection": 389, "text": "t has been well documented that the increase in strength over the first few weeks of resistance training (i.e. acute) has a strong underlying neural component and further enhancement in strength with long-term (i.e. chronic) resistance training is due to muscle hypertrophy. For", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34052876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Low-intensity blood flow restricted (LI-BFR) resistance training has been shown to produce comparable increases in muscle hypertrophy to traditional high-intensity (HI) resistance training. Ho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21445603", "endSection": "abstract" }, { "offsetInBeginSection": 643, "offsetInEndSection": 955, "text": "r adaptations caused by resistance training include increased cross-sectional area of the muscle (hypertrophy, hyperplasia, or both), selective hypertrophy of fast twitch fibers, decreased or maintained mitochondrial number and capillary density of muscle, and possible changes in energy sources. Changes in nerv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18796867", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Skeletal muscle hypertrophy following resistance training is accompanied by a fiber type-specific increase in satellite cell content in elderly men", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19196907", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "High-intensity resistance (HIR) training has been associated with muscle hypertrophy and decreased microvascular density that might produce a blood flow limitation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8792025", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 446, "text": "The rate and amount of muscle hypertrophy associated with resistance training is influenced by a wide array of variables including the training program, plus training experience, gender, genetic predisposition, and nutritional status of the individual", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31482093", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1520, "text": "CONCLUSION: The results of this study suggest that pBFR can stimulate muscle hypertrophy to the same degree to that of high-intensity resistance trainin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24188499", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "It is universally accepted that resistance training promotes increases in muscle strength and hypertrophy in younger and older populations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32162291", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Resistance training (RT) is a popular method of conditioning to enhance sport performance as well as an effective form of exercise to attenuate the age-mediated decline in muscle strength and mass", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12392444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28663372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Resistance training increases muscle size (i.e., causes hypertrophy) and muscle strength, particularly in untrained individuals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31161403", "endSection": "abstract" }, { "offsetInBeginSection": 129, "offsetInEndSection": 255, "text": "Hypertrophy is widely believed to be one of the mechanisms (i.e., a mediator) by which resistance training increases strength.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31161403", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Chronic resistance training induces increases in muscle fibre cross-sectional area (CSA), otherwise known as hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10932036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "The aim of the study was to determine whether it is possible to improve both maximum and rapid force production using resistance training that is typically used to induce muscle hypertrophy in previously untrained older men.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25911469", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Is an Energy Surplus Required to Maximize Skeletal Muscle Hypertrophy Associated With Resistance Training.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31482093", "endSection": "title" }, { "offsetInBeginSection": 1384, "offsetInEndSection": 1827, "text": "We conclude that resistance training of prediabetic obese subjects is effective at changing muscle, resulting in fiber hypertrophy and increased type IIx fiber content, and these changes continue up to 16 wk of training.NEW & NOTEWORTHY Obese, insulin-resistant men responded to 16 wk of progressive resistance training with muscle hypertrophy and increased strength and a shift in muscle fiber composition toward fast-twitch, type IIx fibers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28663372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "BACKGROUND: Effects of resistance training on muscle strength and hypertrophy are well established in adults and youn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32740889", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 897, "text": "Increments in the cross-sectional area of muscle after resistance training can be primarily attributed to fibre hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8153497", "endSection": "abstract" }, { "offsetInBeginSection": 409, "offsetInEndSection": 757, "text": "However, no data are reported in the literature to describe and compare the efficacy of the different hypertrophic resistance training strategies in hypoxia.Moreover, improvements in sprinting, jumping, or throwing performance have also been described at terrestrial altitude, encouraging research into the speed of explosive movements at altitude.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28315193", "endSection": "abstract" }, { "offsetInBeginSection": 1170, "offsetInEndSection": 1384, "text": "We conclude that a program of resistance exercise can be safely carried out by elderly women, such a program significantly increases muscle strength, and such gains are due, at least in part, to muscle hypertrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1864770", "endSection": "abstract" } ] }, { "body": "Which company developed Waylivra?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31301033" ], "ideal_answer": [ "Waylivra is being developed by Ionis Pharmaceuticals through its subsidiary company, Akcea Therapeutics." ], "exact_answer": [ "Ionis Pharmaceuticals", "Akcea Therapeutics" ], "type": "factoid", "id": "626aeba1e764a53204000040", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 312, "text": "Volanesorsen (Waylivra\u00ae), an antisense oligonucleotide inhibitor of apolipoprotein CIII (apoCIII) mRNA, is being developed by Ionis Pharmaceuticals through its subsidiary company, Akcea Therapeutics, to treat familial chylomicronemia syndrome (FCS), hypertriglyceridemia and familial partial lipodystrophy (FPL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31301033", "endSection": "abstract" } ] }, { "body": "Is nerinetide effective for ischaemic stroke?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32087818" ], "ideal_answer": [ "No. Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo." ], "exact_answer": "no", "type": "yesno", "id": "61f93cc7882a024a1000004c", "snippets": [ { "offsetInBeginSection": 2391, "offsetInEndSection": 2613, "text": "337 (61\u00b74%) of 549 patients with nerinetide and 329 (59\u00b72%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1\u00b704, 95% CI 0\u00b796-1\u00b714; p=0\u00b735). Secondary outcomes were similar between groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32087818", "endSection": "abstract" }, { "offsetInBeginSection": 2799, "offsetInEndSection": 2975, "text": "INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32087818", "endSection": "abstract" }, { "offsetInBeginSection": 2713, "offsetInEndSection": 2997, "text": " patients receiving alteplase. Serious adverse events occurred equally between groups.INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.FUNDING: Canadian Inst", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32087818", "endSection": "abstract" } ] }, { "body": "What is known about FANK1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20978819", "http://www.ncbi.nlm.nih.gov/pubmed/31086747", "http://www.ncbi.nlm.nih.gov/pubmed/17604233", "http://www.ncbi.nlm.nih.gov/pubmed/24369145" ], "ideal_answer": [ "Fank1 encodes a protein containing a fibronectin type III domain in the amino terminus and five ankyrin repeats in its carboxyl terminus. FANK1 displays a high degree of sequence conservation in 11 vertebrate species during evolution. Bioinformatic and experimental analyses revealed that Fank1 was exclusively expressed in the testis in both mice and humans.\nConsistent with its nuclear localization, a gene ontology analysis suggests that FANK1 has a DNA binding activity and thus may function as a transcription factor." ], "type": "summary", "id": "624c97cde764a53204000005", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 146, "text": "The fibronectin type 3 and ankyrin repeat domains 1 gene, Fank1, is an ancient, evolutionarily conserved gene present in vertebrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31086747", "endSection": "abstract" }, { "offsetInBeginSection": 315, "offsetInEndSection": 579, "text": "Fank1, a novel gene highly expressed in testis, functioned as an anti-apoptotic protein that activated the activator protein 1 (AP-1) pathway. We found that Jab1 (Jun activation domain-binding protein 1), a co-activator of AP-1, specifically interacted with Fank1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20978819", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 424, "text": " Fank1, which encodes a protein containing a fibronectin type III domain in the amino terminus and five ankyrin repeats in its carboxyl terminus. FANK1 displays a high degree of sequence conservation in 11 vertebrate species during evolution. Bioinformatic and experimental analyses revealed that Fank1 was exclusively expressed in the testis in both mice and humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17604233", "endSection": "abstract" }, { "offsetInBeginSection": 620, "offsetInEndSection": 783, "text": " Consistent with its nuclear localization, a gene ontology analysis suggests that FANK1 has a DNA binding activity and thus may function as a transcription factor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17604233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Testis-specific Fank1 gene in knockdown mice produces oligospermia via apoptosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24369145", "endSection": "title" } ] }, { "body": "Please list the drugs associated with Drug-Induced Hypophosphatemia.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33638305", "http://www.ncbi.nlm.nih.gov/pubmed/8069002", "http://www.ncbi.nlm.nih.gov/pubmed/33146741", "http://www.ncbi.nlm.nih.gov/pubmed/33051909", "http://www.ncbi.nlm.nih.gov/pubmed/26939882", "http://www.ncbi.nlm.nih.gov/pubmed/33237342", "http://www.ncbi.nlm.nih.gov/pubmed/2108845", "http://www.ncbi.nlm.nih.gov/pubmed/32337119", "http://www.ncbi.nlm.nih.gov/pubmed/33146052", "http://www.ncbi.nlm.nih.gov/pubmed/33563894", "http://www.ncbi.nlm.nih.gov/pubmed/31776845", "http://www.ncbi.nlm.nih.gov/pubmed/20356849", "http://www.ncbi.nlm.nih.gov/pubmed/34534708", "http://www.ncbi.nlm.nih.gov/pubmed/32730387", "http://www.ncbi.nlm.nih.gov/pubmed/17117416", "http://www.ncbi.nlm.nih.gov/pubmed/27613487" ], "ideal_answer": [ "Drug induced hypophosphatemia can occur with iron therapy as well a treatment with ferric carboxymaltose, elotuzumab, cemiplimab, Temsirolimus, capecitabine, panobinostat, bendamustine, ofatumumab, carboplatin and etoposide (BOCE)" ], "exact_answer": [ [ "Ferric carboxymaltose", "iron" ], [ "elotuzumab" ], [ "cemiplimab" ], [ "bendamustine", "BOCE" ], [ "ofatumumab" ], [ "carboplatin" ], [ "etopside" ], [ "Temsirolimus" ], [ "capecitabine" ], [ "panobinostat" ] ], "type": "list", "id": "625ebc98e764a53204000030", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 351, "text": "Contemporary intravenous iron formulations allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important but underappreciated complication of certain formulations is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34534708", "endSection": "abstract" }, { "offsetInBeginSection": 1163, "offsetInEndSection": 1303, "text": "Persistent hypophosphatemia can occur with iron therapy and can cause debilitating diseases including myopathy, osteomalacia and fractures. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34534708", "endSection": "abstract" }, { "offsetInBeginSection": 1308, "offsetInEndSection": 1449, "text": "review summarizes the current understanding of the iron-phosphate axis as well as complications of intravenous iron-induced hypophosphatemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34534708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Hypophosphatemia Is Common After Intravenous Ferric Carboxymaltose Infusion Among Patients With Symptomatic Heart Failure With Reduced Ejection Fraction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33051909", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Administration of intravenous ferric carboxymaltose (FCM) for iron-deficient patients suffering heart failure with reduced ejection fraction (HFrEF) has been associated with transient hypophosphatemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33051909", "endSection": "abstract" }, { "offsetInBeginSection": 1209, "offsetInEndSection": 1302, "text": "Biochemically relevant hypophosphatemia is common following a single dose of intravenous FCM.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33051909", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The purpose of this single-center retrospective study was to determine the incidence of decreased blood phosphorus levels and hypophosphatemia among multiple myeloma (MM) patients treated with elotuzumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33237342", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 133, "text": "requent occurrence of hypophosphatemia among multiple myeloma patients treated with elotuzumab: a single clinic retrospective study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33237342", "endSection": "title" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1714, "text": "This retrospective study suggests that hypophosphatemia commonly occurs among MM patients receiving elotuzumab-containing therapies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33237342", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 1098, "text": "The most common treatment-emergent adverse events (TEAEs) of any grade were contact dermatitis, rash, and viral upper respiratory tract infection (each n\u2009=\u20093, 23.1%). Five grade\u2009\u2265\u20093 TEAEs were reported in four patients: autoimmune colitis, dehydration, hyponatremia, hypophosphatemia, and muscular weakness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33146741", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 1085, "text": "The most common non-hematologic grade 3-4 toxicities were neutropenic fever and hypophosphatemia. There were no treatment-related deaths. In conclusion, BOCE is a safe and effective outpatient salvage regimen for patients with RR NHL and serves as an effective bridge to stem cell transplantation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33146052", "endSection": "abstract" }, { "offsetInBeginSection": 742, "offsetInEndSection": 982, "text": "orty-five patients were enrolled and 41 were evaluable\u00a0for dose-limiting toxicities (DLTs). The most common adverse events (AEs) were mucositis, fatigue, and thrombocytopenia. The most common grade 3/4 AEs were hypophosphatemia and anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33638305", "endSection": "abstract" }, { "offsetInBeginSection": 587, "offsetInEndSection": 998, "text": "Six dose-limiting toxicities were reported (mostly hematological); maximum tolerated dose of panobinostat (primary endpoint) was 10\u2009mg. Most common adverse events (AEs) were diarrhea (60%) and peripheral neuropathy (60%); all grade 1/2. Grade 3/4 AEs occurred in 80% of patients and included decreased neutrophil (45%), platelet (25%) and white blood cell (25%) counts, anemia (25%) and hypophosphatemia (25%). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33563894", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1079, "text": "As treatment with imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730387", "endSection": "abstract" }, { "offsetInBeginSection": 1292, "offsetInEndSection": 1389, "text": "Other drugs such as immunomodulators or methotrexate have been also associated with hyponatremia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26939882", "endSection": "abstract" }, { "offsetInBeginSection": 589, "offsetInEndSection": 823, "text": "Alkylating agents have been linked with the occurrence of hyponatremia [due to syndrome of inappropriate antidiuretic hormone secretion (SIADH)] and Fanconi's syndrome (hypophosphatemia, aminoaciduria, hypouricemia and/or glucosuria).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26939882", "endSection": "abstract" }, { "offsetInBeginSection": 917, "offsetInEndSection": 1119, "text": "catecholamines, beta-adrenergic agonists, sodium bicarbonate, and acetazolamide are commonly used therapeutic agents that could contribute significantly to the development of hypophosphatemia. Provision", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8069002", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 385, "text": "Hypophosphatemia, defined as serum phosphate levels below 2.5\u00a0mg/dL (0.81\u00a0mmol/L), is frequently observed in the course of treatment with commonly used drugs, such as diuretics, bisphosphonates, antibiotics, insulin, and antacids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776845", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Imatinib mesylate induces hypophosphatemia in patients with chronic myeloid leukemia in late chronic phase, and this effect is associated with response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17117416", "endSection": "title" }, { "offsetInBeginSection": 793, "offsetInEndSection": 1078, "text": "ypophosphatemia was significantly higher among COPD patients taking one or more drugs commonly used in COPD and known as negatively influencing renal phosphate handling: xanthine derivatives, corticosteroids, loop diuretics, and beta 2-adrenergic bronchodilators. Short-term administra", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2108845", "endSection": "abstract" }, { "offsetInBeginSection": 159, "offsetInEndSection": 396, "text": "phosphatemia, defined as serum phosphate levels below 2.5\u00a0mg/dL (0.81\u00a0mmol/L), is frequently observed in the course of treatment with commonly used drugs, such as diuretics, bisphosphonates, antibiotics, insulin, and antacids. Furthermor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776845", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 1097, "text": "ns and patients should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses of specific intravenous iron formulations. Sympto", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34534708", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 367, "text": "ct, hypophosphatemia frequently develops in the course of treatment with drugs used in every-day clinical practice including diuretics and bisphosphonates. Prop", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20356849", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 62, "text": "ypophosphatemia induced by carboxymaltose iron and imatinib.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730387", "endSection": "title" }, { "offsetInBeginSection": 212, "offsetInEndSection": 282, "text": "ere hypophosphatemia from daily marijuana use is a rare side-effect. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32337119", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 644, "text": "ceiving intravenous carboxymaltose iron in one occasion due to refractory anemia, she developed symptomatic hypophosphatemia. Urinary", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730387", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1093, "text": "ith imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake. These cases i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "[Hypophosphatemia induced by carboxymaltose iron and imatinib. Report of two cases].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32730387", "endSection": "title" }, { "offsetInBeginSection": 202, "offsetInEndSection": 361, "text": "In fact, hypophosphatemia frequently develops in the course of treatment with drugs used in every-day clinical practice including diuretics and bisphosphonates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20356849", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 385, "text": "1\u00a0mmol/L), is frequently observed in the course of treatment with commonly used drugs, such as diuretics, bisphosphonates, antibiotics, insulin, and antacids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31776845", "endSection": "abstract" }, { "offsetInBeginSection": 906, "offsetInEndSection": 1107, "text": " Antacids, catecholamines, beta-adrenergic agonists, sodium bicarbonate, and acetazolamide are commonly used therapeutic agents that could contribute significantly to the development of hypophosphatemi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8069002", "endSection": "abstract" }, { "offsetInBeginSection": 1390, "offsetInEndSection": 1503, "text": "The administration of estrogens at high doses, streptozocin, azacitidine and suramin may induce hypophosphatemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26939882", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "INTRODUCTION: Tenofovir disoproxil fumarate (TDF) -containing regimens have been associated with nephrotoxicity and hypophosphatemia in HIV-infe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27613487", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 451, "text": "We report here that imatinib induces hypophosphatemia in a high proportion of our series of CML patients previously treated with interferon alpha, and that this previously unreported side effect is associated with response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17117416", "endSection": "abstract" } ] }, { "body": "Is Algenpantucel-L effective for pancreatic cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23229886", "http://www.ncbi.nlm.nih.gov/pubmed/33630475" ], "ideal_answer": [ "No. In phase 3 clinical trial Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable pancreatic cancer receiving SOC neoadjuvant chemotherapy and chemoradiation." ], "exact_answer": "no", "type": "yesno", "id": "61f938e7882a024a10000049", "snippets": [ { "offsetInBeginSection": 1099, "offsetInEndSection": 1824, "text": " Median (IQR) overall survival was 14.9 (12.2-17.8) months in the standard group (N=158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) (hazard ratio [HR] 1.02, 95% CI 0.66-1.58; P = 0.98). Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% CI 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05).CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33630475", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1128, "text": "CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229886", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1078, "text": "CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve surviva", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23229886", "endSection": "abstract" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1822, "text": "CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiatio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33630475", "endSection": "abstract" } ] }, { "body": "Is Mical an oxidoreductase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31949908", "http://www.ncbi.nlm.nih.gov/pubmed/12700098", "http://www.ncbi.nlm.nih.gov/pubmed/27223600", "http://www.ncbi.nlm.nih.gov/pubmed/33671465" ], "ideal_answer": [ "Yes,\nMICAL is an oxidoreductase" ], "exact_answer": "yes", "type": "yesno", "id": "62515021e764a53204000018", "snippets": [ { "offsetInBeginSection": 282, "offsetInEndSection": 497, "text": "the MICALs, which are flavoprotein monooxygenase/hydroxylase enzymes that associate with flavin adenine dinucleotide (FAD) and use the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH) in Redox reactions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33671465", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 26, "text": "MICAL is an oxidoreductase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31949908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "We have recently identified a new family of multidomain oxidoreductase (redox) enzymes, the MICALs,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27223600", "endSection": "abstract" }, { "offsetInBeginSection": 1552, "offsetInEndSection": 1576, "text": "the oxidoreductase MICAL", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12700098", "endSection": "abstract" } ] }, { "body": "What is the most frequent evolution (next stage) when Aortic intramural hematoma (IMH) is not treated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29945807", "http://www.ncbi.nlm.nih.gov/pubmed/10585078", "http://www.ncbi.nlm.nih.gov/pubmed/19793400", "http://www.ncbi.nlm.nih.gov/pubmed/25512883", "http://www.ncbi.nlm.nih.gov/pubmed/29274600", "http://www.ncbi.nlm.nih.gov/pubmed/32652687", "http://www.ncbi.nlm.nih.gov/pubmed/12874185", "http://www.ncbi.nlm.nih.gov/pubmed/15710757", "http://www.ncbi.nlm.nih.gov/pubmed/15066238", "http://www.ncbi.nlm.nih.gov/pubmed/25087203", "http://www.ncbi.nlm.nih.gov/pubmed/32668075", "http://www.ncbi.nlm.nih.gov/pubmed/10567317" ], "ideal_answer": [ "Aortic intramural hematoma (IMH) evolves very dynamically in the short-term to regression, dissection, or aortic rupture", "Intramural hematoma IMH may progress to classic dissection, frank rupture, or aneurysmal dilation." ], "exact_answer": [ "aortic dissection", "aortic type A dissection", "dissecting aneurysm", "classic aortic dissection" ], "type": "factoid", "id": "625ebf76e764a53204000033", "snippets": [ { "offsetInBeginSection": 1442, "offsetInEndSection": 1605, "text": "We consider that IMH may represent a part of a disease (aortic dissection), depicted by radiological images in a specific single instant of its clinical evolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29274600", "endSection": "abstract" }, { "offsetInBeginSection": 632, "offsetInEndSection": 765, "text": "IMH may progress to classic dissection, frank rupture, or aneurysmal dilation; yet, IMH may also regress and be completely resorbed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32652687", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 349, "text": "Type B acute aortic dissection (AAD) and intramural hematoma (IMH) can both present as potentially catastrophic lesions of the descending aorta. IMH is distinguished from AAD by the absence of an intimal tear and flap. With short-term outcomes being similar to type B AAD, IMH is treated identically to AAD in the corresponding segment of the aorta.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668075", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 151, "text": "Intramural hematomas (IMHs) are reported to dynamically evolve into different clinical outcomes ranging from regression to aortic rupture, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29945807", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 643, "text": " IMH displays a typical of dissection progress, and could be considered as a precursor of classic aortic dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19793400", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 132, "text": " Aortic intramural hematoma (IMH) evolves very dynamically in the short-term to regression, dissection, or aortic rupture", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12874185", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Intramural hematoma of the aorta is a condition increasingly observed in clinical practice. Uncertainty exists whether such lesions represent a different pathology or simply the precursors of classic dissecting aneurysm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10585078", "endSection": "abstract" }, { "offsetInBeginSection": 666, "offsetInEndSection": 816, "text": "We stress that intramural hematoma of the ascending aorta has to be managed as an aortic type A dissection and that aggressive treatment is advisable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10585078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "BACKGROUND: Aortic intramural hematoma (IMH) evolves very dynamically in the short-term to regression, dissection, or aortic rupture.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12874185", "endSection": "abstract" }, { "offsetInBeginSection": 1281, "offsetInEndSection": 1379, "text": "LUSIONS: The most frequent long-term evolution of IMH is to aortic aneurysm or pseudoaneurysm. Com", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12874185", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 336, "text": "IMH also frequently leads to aortic emergency, which can be fatal unless rapidly diagnosed and treated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25512883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Aortic intramural hematoma (IMH) is an acute, potentially lethal disorder that is similar to but pathologically distinct from acute aortic dissection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15066238", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "BACKGROUND: It has been reported that early surgery should be required for patients with type A aortic intramural hematoma (IMH) because it tends to develop classic aortic dissection ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10567317", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND: Aortic intramural hematoma (IMH) evolves very dynamically in the short-term to regression, dissection, or aortic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12874185", "endSection": "abstract" }, { "offsetInBeginSection": 312, "offsetInEndSection": 481, "text": "ome cases there is partial or complete regression of the hematoma under medical treatment, but most progress to dissection, aneurysmal dilatation or aortic rupture. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25087203", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1098, "text": "ase evolution, IMH may progress to classic AD, frank rupture, or aneurysmal dilation; yet, IMH may also regress and be completely resorbed. However, since the nat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32668075", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1373, "text": "CONCLUSIONS: The most frequent long-term evolution of IMH is to aortic aneurysm or pseudoaneurys", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12874185", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 918, "text": " later developed pseudoaneurysm. At the end of follow-up, the IMH had regressed completely without dilatation in 17 patients (34%), progressed to classical dissection in 6 (12%), evolved to fusiform aneurysm in 11 (22%), evolved to saccular aneurysm in 4 (8%), and evolv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12874185", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the Qtern pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29176433", "http://www.ncbi.nlm.nih.gov/pubmed/32454718", "http://www.ncbi.nlm.nih.gov/pubmed/28884600", "http://www.ncbi.nlm.nih.gov/pubmed/28176222" ], "ideal_answer": [ "Qtern pill includes saxagliptin and dapagliflozin. It is indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus." ], "exact_answer": [ [ "saxagliptin" ], [ "dapagliflozin" ] ], "type": "list", "id": "61fbc3d5c9dfcb9c0900000e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Objectives: The fixed dose combination of saxagliptin and dapagliflozin is a recently approved antidiabetic medication. It is marketed under the brand name Qtern. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32454718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) tablets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 429, "text": "Saxagliptin/dapagliflozin fixed-dose combination tablets (Qtern\u00ae) are indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus (T2DM), either when treatment with metformin and/or a sulfonylurea plus a monocomponent of saxagliptin/dapagliflozin provides inadequate glycaemic control, or when the patient is already being treated with the free combination of saxagliptin\u00a0+\u00a0dapagliflozin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28176222", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 269, "text": "This article highlights the following new drugs: brodalumab (Siliq), dapagliflozin and saxagliptin (Qtern), dupilumab (Dupixent), oxymetazoline (Rhofade), safinamide (Xadago), and sarilumab (Kevzara).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29176433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) table", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884600", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) tablet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884600", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1686, "text": "CONCLUSION: QTERN (dapagliflozin/saxagliptin) tablets are a reasonable option for patients with T2DM not controlled on metformin, but cost, insurance coverage, and a lackluster reduction in A1C will likely limit its use until more data regarding its effects on complications of diabetes and cardiovascular outcomes become availabl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884600", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 268, "text": "This article highlights the following new drugs: brodalumab (Siliq), dapagliflozin and saxagliptin (Qtern), dupilumab (Dupixent), oxymetazoline (Rhofade), safinamide (Xadago), and sarilumab (Kevzara)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29176433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 287, "text": "OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) tablets.DATA SOURCES: Searches of MEDLINE (1946 to July 1, 2017) were conducted using the keywords QTERN, saxagl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884600", "endSection": "abstract" }, { "offsetInBeginSection": 1219, "offsetInEndSection": 1598, "text": "nd dapagliflozin + metformin was -0.27 (95% CI = -0.48 to -0.05, P = 0.0166). The combination was well tolerated when added to metformin.CONCLUSION: QTERN (dapagliflozin/saxagliptin) tablets are a reasonable option for patients with T2DM not controlled on metformin, but cost, insurance coverage, and a lackluster reduction in A1C will likely limit its use until more data regard", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28884600", "endSection": "abstract" } ] }, { "body": "List SLE-related autoantibodies.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29156741", "http://www.ncbi.nlm.nih.gov/pubmed/11093143", "http://www.ncbi.nlm.nih.gov/pubmed/30526327", "http://www.ncbi.nlm.nih.gov/pubmed/31899518", "http://www.ncbi.nlm.nih.gov/pubmed/29141377" ], "ideal_answer": [ "Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies).\nDiagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected." ], "exact_answer": [ [ "lupus anticoagulant" ], [ "anticardiolipine" ], [ "anti-dsDNA" ], [ "anti-SSA" ], [ "anti-SSB" ], [ "anti-RNP" ], [ "anti-Sm" ], [ "anti-RPLP" ], [ "anti-SNRPC" ], [ "anti-PARP1" ], [ "anti-RPLP2" ] ], "type": "list", "id": "624de6dce764a53204000009", "snippets": [ { "offsetInBeginSection": 1337, "offsetInEndSection": 1559, "text": "Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31899518", "endSection": "abstract" }, { "offsetInBeginSection": 550, "offsetInEndSection": 827, "text": "Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30526327", "endSection": "abstract" }, { "offsetInBeginSection": 869, "offsetInEndSection": 970, "text": " SLE related autoantibodies including AnuA, anti-dsDNA, Acl, anti-nRNP, anti-rRNP and anti-Smantibody", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29141377", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1401, "text": "SLE patients were acidic ribosomal phosphoprotein (P0)-4, acidic ribosomal phosphoprotein (P0)-11, DNA topoisomerase 1 (full length)-1, and U1-SnRNP 68/70 KDa-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29156741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "The association of anti-nuclear antigen (ANA) and anti-cardiolipin (CL) antibodies is often observed during systemic lupus erythematosus (SLE) or the primary anti-phospholipid syndrome, thereby raising the possibility of a relationship between these two autoantibody populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11093143", "endSection": "abstract" } ] }, { "body": "What is nephropathic cystinosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31548351", "http://www.ncbi.nlm.nih.gov/pubmed/7494397", "http://www.ncbi.nlm.nih.gov/pubmed/10210897", "http://www.ncbi.nlm.nih.gov/pubmed/26565940", "http://www.ncbi.nlm.nih.gov/pubmed/10673275", "http://www.ncbi.nlm.nih.gov/pubmed/11516611", "http://www.ncbi.nlm.nih.gov/pubmed/31361240", "http://www.ncbi.nlm.nih.gov/pubmed/12204010", "http://www.ncbi.nlm.nih.gov/pubmed/8644713", "http://www.ncbi.nlm.nih.gov/pubmed/32564281", "http://www.ncbi.nlm.nih.gov/pubmed/24077756", "http://www.ncbi.nlm.nih.gov/pubmed/9286148", "http://www.ncbi.nlm.nih.gov/pubmed/33575541", "http://www.ncbi.nlm.nih.gov/pubmed/14610675", "http://www.ncbi.nlm.nih.gov/pubmed/25345100", "http://www.ncbi.nlm.nih.gov/pubmed/31570786", "http://www.ncbi.nlm.nih.gov/pubmed/25526929", "http://www.ncbi.nlm.nih.gov/pubmed/25811383", "http://www.ncbi.nlm.nih.gov/pubmed/20865335", "http://www.ncbi.nlm.nih.gov/pubmed/28793998", "http://www.ncbi.nlm.nih.gov/pubmed/33975805", "http://www.ncbi.nlm.nih.gov/pubmed/29806685", "http://www.ncbi.nlm.nih.gov/pubmed/27181776", "http://www.ncbi.nlm.nih.gov/pubmed/10625078", "http://www.ncbi.nlm.nih.gov/pubmed/12795432", "http://www.ncbi.nlm.nih.gov/pubmed/29905968", "http://www.ncbi.nlm.nih.gov/pubmed/34237326", "http://www.ncbi.nlm.nih.gov/pubmed/10556299", "http://www.ncbi.nlm.nih.gov/pubmed/25071085", "http://www.ncbi.nlm.nih.gov/pubmed/19705160", "http://www.ncbi.nlm.nih.gov/pubmed/11528232", "http://www.ncbi.nlm.nih.gov/pubmed/15583946", "http://www.ncbi.nlm.nih.gov/pubmed/28629674" ], "ideal_answer": [ "Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by abnormal accumulation of intracellular cystine in various tissues including the brain, kidneys, bones, and eyes.", "Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein.", "Cystinosis is an autosomal recessive lysosomal storage disorder. It is caused by mutations in the CTNS gene, which encodes the cystinosin protein. In cases of cystinoin deficiency, free cystine accumulates in lyssomes and forms toxic crystals." ], "type": "summary", "id": "625ebe5ce764a53204000032", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Cystinosis is an autosomal recessive lysosomal storage disorder caused by CTNS gene mutations. The CTNS gene encodes the protein cystinosin, which transports free cystine from lysosomes to cytoplasm. In cases of cystinosin deficiency, free cystine accumulates in lysosomes and forms toxic crystals that lead to tissue and organ damage", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32564281", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 340, "text": "Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by abnormal accumulation of intracellular cystine in various tissues including the brain, kidneys, bones, and eyes. Infantile nephropathic cystinosis is the most severe phenotype of cystinosis that has been associated with a wide spectrum of ocular features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33575541", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 118, "text": "Nephropathic cystinosis is characterized by an accumulation of cystine crystals within most body tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12795432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "Nephropathic cystinosis is a rare autosomal recessive lysosomal disease characterized by accumulation of pathognomonic cystine crystals in renal and other tissues of the body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31361240", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 254, "text": " Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26565940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Nephropathic cystinosis is characterized clinically by generalized proximal renal tubular dysfunction, renal Fanconi Syndrome and progressive renal failure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19705160", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Nephropathic cystinosis is a severe, monogenic systemic disorder that presents early in life and leads to progressive organ damage, particularly affecting the kidneys.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33975805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Nephropathic cystinosis, characterized by accumulation of cystine in the lysosomes, is caused by mutations in CTNS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25071085", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Nephropathic cystinosis is a hereditary disorder characterized by a specific defect in the transport of cystine across the lysosomal membrane, leading to an accumulation of protein-free cystine in tissues, including conjunctiva, liver, bone marrow and kidney.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10210897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Nephropathic cystinosis is one of the only lysosomal storage diseases for which there is an effective therapy against the basic, pathologic process-cystine accumulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9286148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Nephropathic cystinosis is a genetic disorder in which the amino acid cystine accumulates in lysosomes, resulting in multiorgan dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11516611", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Nephropathic cystinosis is a rare lysosomal storage disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29905968", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Nephropathic cystinosis is a rare, inherited metabolic disease caused by functional defects of cystinosin associated with mutations in the CTNS gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20865335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Nephropathic cystinosis is a rare disease secondary to recessive mutations of the CTNS gene encoding the lysosomal cystine transporter cystinosin, causing accumulation of cystine in multiple organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34237326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Nephropathic cystinosis is an autosomal recessive metabolic, lifelong disease characterized by lysosomal cystine accumulation throughout the body that commonly presents in infancy with a renal Fanconi syndrome and, if untreated, leads to end-stage kidney disease (ESKD) in the later childhood years. The mo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27181776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Nephropathic cystinosis is a hereditary disorder characterized by a specific defect in the transport of cystine across the lysosomal membrane, leading to an accumulation of protein-free cystine in tissues, including conjunctiva, liver, bone marrow and kidney. Renal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10210897", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "BACKGROUND AND OBJECTIVES: Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28793998", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 258, "text": "Infantile nephropathic cystinosis is an autosomal recessive disorder characterized biochemically by an abnormally high intracellular content of free cystine in different organs and tissues due to a transport defect of cystine through the lysosomal membrane. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8644713", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. E", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25811383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 246, "text": "BACKGROUND: Deletions or inactivating mutations of the cystinosin gene CTNS lead to cystine accumulation and crystals at acidic pH in patients with nephropathic cystinosis, a rare lysosomal storage disease and the main cause of hereditary renal F", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31548351", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "OBJECTIVE: Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26565940", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Infantile nephropathic cystinosis, an inborn error of metabolism with an autosomal recessive inheritance pattern, is characterized by lysosomal storage of the amino acid cystine due to an impaired transport of cystine out of the lysosomes. Ini", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11528232", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder, which causes loss of renal proximal tubular function and progressive loss of glomerular function, finally leading to end stage renal failure at school age. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31570786", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Nephropathic cystinosis is one of the only lysosomal storage diseases for which there is an effective therapy against the basic, pathologic process-cystine accumulation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9286148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Nephropathic cystinosis is a severe, monogenic systemic disorder that presents early in life and leads to progressive organ damage, particularly affecting the kidneys", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33975805", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder in which intracellular cystine accumulates", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24077756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Nephropathic cystinosis is a rare autosomal recessive lysosomal disease characterized by accumulation of pathognomonic cystine crystals in renal and other tissues of the body", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31361240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Nephropathic cystinosis is a severe autosomal recessive inherited metabolic disease characterized by accumulation of free cystine in lysosomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15583946", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "BACKGROUND AND OBJECTIVES: Nephropathic cystinosis is a lysosomal storage disorder characterized by renal tubular Fanconi syndrome in infancy and glomerular damage leading to renal f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25526929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Nephropathic cystinosis is a rare lysosomal storage disorder caused by mutations in the CTNS gene ncoding the lysosomal cystine transporter cystinosin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25345100", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "UNLABELLED: Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder in which intracellular cystine accumulates due to impaired transport out o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14610675", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Nephropathic cystinosis is an autosomal recessive lysosomal disease in which cystine cannot exit the lysosome to complete its degradation in the cytoplasm, thus accumulating in tissues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28629674", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Nephropathic cystinosis is an autosomal recessive inborn error of metabolism characterized by the lysosomal storage of the disulphide amino acid cystine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7494397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Nephropathic cystinosis is an autosomal recessive disorder caused by the defective transport of cystine out of lysosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10673275", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Nephropatic cystinosis (NC) is a rare disease associated with pathogenic variants in the CTNS gene, with a common variant that consists of a 57kb-deletion involving CTNS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29806685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Ocular nonnephropathic cystinosis, a variant of the classic nephropathic type of cystinosis, is an autosomal recessive lysosomal storage disorder characterized by photophobia due to corneal cystine crystals but absence of renal disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10625078", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 221, "text": "Infantile nephropathic cystinosis is a rare, autosomal recessive disease caused by a defect in the transport of cystine across the lysosomal membrane and characterized by early onset of renal proximal tubular dysfunction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10556299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "The autosomal recessive lysosomal storage disorder, nephropathic cystinosis is characterized by impaired transport of free cystine out of lysosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12204010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Nephropathic cystinosis is a severe autosomal recessive inherited metabolic disease characterized by accumulation of free cystine in lysosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15583946", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the Contrave pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22860172", "http://www.ncbi.nlm.nih.gov/pubmed/19885278", "http://www.ncbi.nlm.nih.gov/pubmed/26679384", "http://www.ncbi.nlm.nih.gov/pubmed/26105116", "http://www.ncbi.nlm.nih.gov/pubmed/25258511", "http://www.ncbi.nlm.nih.gov/pubmed/30991059", "http://www.ncbi.nlm.nih.gov/pubmed/26957883", "http://www.ncbi.nlm.nih.gov/pubmed/34745784", "http://www.ncbi.nlm.nih.gov/pubmed/25661549", "http://www.ncbi.nlm.nih.gov/pubmed/25395816", "http://www.ncbi.nlm.nih.gov/pubmed/27773782", "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "http://www.ncbi.nlm.nih.gov/pubmed/20509712", "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "http://www.ncbi.nlm.nih.gov/pubmed/29408463", "http://www.ncbi.nlm.nih.gov/pubmed/29151591", "http://www.ncbi.nlm.nih.gov/pubmed/28130024" ], "ideal_answer": [ "Contrave\u00ae is an adjunct pharmacotherapy for obesity that contains bupropion (BUP) and naltrexone (NTX)." ], "exact_answer": [ [ "bupropion" ], [ "naltrexone" ] ], "type": "list", "id": "61f7d15d882a024a10000031", "snippets": [ { "offsetInBeginSection": 126, "offsetInEndSection": 418, "text": "Bupropion is indicated for major depressive disorder (Wellbutrin\u00ae, GlaxoSmithKline, Research Triangle Park, NC), smoking cessation (Zyban\u00ae, GlaxoSmithKline, Research Triangle Park, NC), and weight loss (when in formulation with naltrexone ER; Contrave\u00ae, Orixegen Therapeutics, La Jolla, CA). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34745784", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "A fixed dose combination of bupropion (BPP) and naltrexone (NTX), Contrave\u00ae, is an FDA approved pharmacotherapy for the treatment of obesity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30991059", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 925, "text": "METHODS: We examined coverage for phentermine, diethylpropion, phendimetrazine, Benzphentamine, Lorcaserin, Phentermine/Topiramate (Qysmia), Liraglutide (Saxenda) and Buproprion/Naltrexone (Contrave) among Medicare, Medicaid and marketplace insurance plans in 34 states.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29151591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Contrave\u00ae is an adjunct pharmacotherapy for obesity that contains bupropion (BUP) and naltrexone (NTX). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29408463", "endSection": "abstract" }, { "offsetInBeginSection": 657, "offsetInEndSection": 927, "text": "THODS: We examined coverage for phentermine, diethylpropion, phendimetrazine, Benzphentamine, Lorcaserin, Phentermine/Topiramate (Qysmia), Liraglutide (Saxenda) and Buproprion/Naltrexone (Contrave) among Medicare, Medicaid and marketplace insurance plans in 34 states.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29151591", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 698, "text": "These include combinations (at low dose) of existing drugs, e.g., bupropion + naltrexone (Contrave), phentermine + topiramate (Qsymia), higher doses of existing drugs licensed for other indications (liraglutide, 3 mg), and new entities (lorcaserin).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25661549", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 962, "text": "CENT FINDINGS: Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "endSection": "abstract" }, { "offsetInBeginSection": 1106, "offsetInEndSection": 1464, "text": "Four combination agent compounds in late stage development include (1) Contrave, which combines long-acting versions of naltrexone and bupropion; (2) Empatic, which combines long-acting bupropion and long-acting zonisamide; (3) Qnexa, which combines phentermine with controlled release topiramate; and (4) an injectable combination of leptin and pramlintide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19885278", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Contrave is an investigational fixed-dose combination drug of naltrexone and bupropion currently in Phase III clinical trials for the treatment of obesity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22860172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "A fixed dose combination of bupropion (BPP) and naltrexone (NTX), Contrave\u00ae, is an FDA approved pharmacotherapy for the treatment of obesity. A re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30991059", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Contrave, under development by Orexigen Therapeutics Inc for the potential treatment of obesity, is an oral, sustained-release combination of the dopamine and norepinephrine reuptake antagonist bupropion and the opioid antagonist naltrexone. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "endSection": "abstract" }, { "offsetInBeginSection": 1524, "offsetInEndSection": 1690, "text": "ts have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia\u00ae) and naltrexone/bupropion (Contrave\u00ae). The current review provides an ove", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27773782", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "In March 2010, Orexigen(R) Therapeutics submitted a new drug application (NDA) for approval of naltrexone sustained release (SR)/bupropion SR (Contrave(R)) for the treatment of obesity in the US. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20509712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "BACKGROUND: We report a case of erythrodermic pustular psoriasis associated with initiation of bupropion/naltrexone (Contrave\u00ae; Orexigen Therapeutics, La Jolla, CA) in a patient with no history of pso", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28130024", "endSection": "abstract" }, { "offsetInBeginSection": 1010, "offsetInEndSection": 1137, "text": "view presented here focuses on naltrexone sustained-release/bupropion sustained-release combination (Contrave(\u00ae)). We conclude ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25258511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Naltrexone/bupropion (Contrave) for weight management; pembrolizumab (Keytruda) for melanoma; dolutegravir/abacavir/lamivudine (Triumeq) for HIV-1; and immune globulin infusion 10% (human) with recombinant human hyaluronidase (Hyqvia) for primary immunodeficiency", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25395816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "Contrave, under development by Orexigen Therapeutics Inc for the potential treatment of obesity, is an oral, sustained-release combination of the dopamine and norepinephrine reuptake antagonist bupropion and the opioid antagonist naltrexone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Contrave\u00ae is an adjunct pharmacotherapy for obesity that contains bupropion (BUP) and naltrexone (NTX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29408463", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Contrave, under development by Orexigen Therapeutics Inc for the potential treatment of obesity, is an oral, sustained-release combination of the dopamine and norepinephrine reuptake antagonist bupropion and the opioid antagonist naltrexone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19777400", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Contrave is an investigational fixed-dose combination drug of naltrexone and bupropion currently in Phase III clinical trials for the treatment of obesity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22860172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26679384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Naltrexone/bupropion ER (Contrave): newly approved treatment option for chronic weight management in obese adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26957883", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "In March 2010, Orexigen(R) Therapeutics submitted a new drug application (NDA) for approval of naltrexone sustained release (SR)/bupropion SR (Contrave(R)) for the treatment of obesity in the US.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20509712", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26957883", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Naltrexone/bupropion: Contrave(R); naltrexone SR/bupropion SR.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20509712", "endSection": "title" }, { "offsetInBeginSection": 494, "offsetInEndSection": 924, "text": "ns are prescribed. Current antiobesity medications and pharmacological strategies will be reviewed.RECENT FINDINGS: Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications ava", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26313898", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 268, "text": "Oral naltrexone extended-release/bupropion extended-release (naltrexone ER/bupropion ER; Contrave(\u00ae), Mysimba(\u2122)) is available as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial body mass index (BMI) of \u2265 30 kg/m(2) (i.e.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26105116", "endSection": "abstract" } ] }, { "body": "When is lorlatinib used?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34589977", "http://www.ncbi.nlm.nih.gov/pubmed/34548910", "http://www.ncbi.nlm.nih.gov/pubmed/34585621" ], "ideal_answer": [ "Lorlatinib is a third-generation ALK inhibitor that can overcome the largest number of acquired ALK resistance mutations, including the solvent-front mutation G1202R." ], "exact_answer": [ "In ALK-positive NSCLC" ], "type": "factoid", "id": "625bb257e764a5320400002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Lorlatinib is a third-generation ALK inhibitor that can overcome the largest number of acquired ALK resistance mutations, including the solvent-front mutation G1202R. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34589977", "endSection": "abstract" }, { "offsetInBeginSection": 80, "offsetInEndSection": 339, "text": "The study tested two medicines called lorlatinib and crizotinib in participants with untreated non-small cell lung cancer that had spread to other parts of their body. All those who took part\u00a0had changes in a gene called ALK, which is involved in cell growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34585621", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1456, "text": " In conclusion, we suggest molecular profiling of progressive tumor disease also for ALK-positive NSCLC to personalize treatment in a subgroup of ALK-positive patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548910", "endSection": "abstract" } ] }, { "body": "Ladybird homeobox (Lbx) transcription factors regulate the development of what body systems/organs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18541024", "http://www.ncbi.nlm.nih.gov/pubmed/12588966", "http://www.ncbi.nlm.nih.gov/pubmed/18056427", "http://www.ncbi.nlm.nih.gov/pubmed/28843494", "http://www.ncbi.nlm.nih.gov/pubmed/9342040", "http://www.ncbi.nlm.nih.gov/pubmed/34411410", "http://www.ncbi.nlm.nih.gov/pubmed/9716535", "http://www.ncbi.nlm.nih.gov/pubmed/24721834", "http://www.ncbi.nlm.nih.gov/pubmed/15136145", "http://www.ncbi.nlm.nih.gov/pubmed/16378763", "http://www.ncbi.nlm.nih.gov/pubmed/22077099", "http://www.ncbi.nlm.nih.gov/pubmed/33786818", "http://www.ncbi.nlm.nih.gov/pubmed/25035933", "http://www.ncbi.nlm.nih.gov/pubmed/19216761" ], "ideal_answer": [ "Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals", "Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals." ], "exact_answer": [ "muscle and nervous system" ], "type": "factoid", "id": "62532ffee764a53204000023", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34411410", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 254, "text": "Lbx/ladybird genes originated as part of the metazoan cluster of Nk homeobox genes. In all animals investigated so far, both the protostome genes and the vertebrate Lbx1 genes were found to play crucial roles in neural and muscle development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18541024", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 261, "text": "The Drosophila ladybird homeobox gene (lad) functions in founder cells of the segmental border muscle to promote myoblast fusion and muscle shaping.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19216761", "endSection": "abstract" }, { "offsetInBeginSection": 648, "offsetInEndSection": 906, "text": "Our data reveal that ladybird not only contributes to the combinatorial code of transcription factors specifying the identity of muscle and cardiac precursors, but also regulates a large number of genes involved in setting cell shape, adhesion, and motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056427", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 419, "text": "A prior genetic analysis showed that during Drosophila muscle and heart development ladybird is required for the specification of a subset of muscular and cardiac precursors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056427", "endSection": "abstract" }, { "offsetInBeginSection": 167, "offsetInEndSection": 391, "text": "The Hmx gene family is a new class of homeobox-containing genes defined by a conserved homeobox region and a characteristic pattern of expression in the central nervous system that is more rostral than that of the Hox genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12588966", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Ladybird (Lbx) homeodomain transcription factors function in neural and muscle development--roles conserved from Drosophila to vertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22077099", "endSection": "abstract" }, { "offsetInBeginSection": 1184, "offsetInEndSection": 1450, "text": "LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24721834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34411410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Ladybird (Lbx) homeodomain transcription factors function in neural and muscle development--roles conserved from Drosophila to vertebrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22077099", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 251, "text": "yofibrils. The Drosophila ladybird homeobox gene (lad) functions in founder cells of the segmental border muscle to promote myoblast fusion and muscl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19216761", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 518, "text": "re we show that the homeobox genes ladybird early and ladybird late are expressed in only one muscle progenitor and its progeny: the segmental border muscle founder cell and two precursors of adult muscles. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9716535", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 420, "text": "prior genetic analysis showed that during Drosophila muscle and heart development ladybird is required for the specification of a subset of muscular and cardiac precursors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Homeobox genes are an evolutionarily conserved class of transcription factors that are critical for development of many organ systems, including the brain and eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25035933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "ladybird, a new component of the cardiogenic pathway in Drosophila required for diversification of heart precursors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9342040", "endSection": "title" }, { "offsetInBeginSection": 211, "offsetInEndSection": 491, "text": "he homeobox containing transcription factor ladybird homeobox 1 (Lbx1) is a central regulator of limb myoblast migration, null mutations of Lbx1 result in severe disruptions to limb muscle formation, particularly in the distal region of the limb in mice (Gross et al., 2000). As s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28843494", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 599, "text": "Lbx1 has been hypothesized to control lateral migration of myoblasts into the distal limb anlage. It act", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28843494", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1469, "text": "that Lbx1 is differentially recruited to the developmental genetic program of inhibitory neurons both within a given tissue and between the DCN and cerebellum. The differential expr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33786818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Phosphorylation of Lbx1 controls lateral myoblast migration into the limb", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28843494", "endSection": "title" }, { "offsetInBeginSection": 648, "offsetInEndSection": 905, "text": "Our data reveal that ladybird not only contributes to the combinatorial code of transcription factors specifying the identity of muscle and cardiac precursors, but also regulates a large number of genes involved in setting cell shape, adhesion, and motility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18056427", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34411410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The ladybird homeobox genes are essential for the specification of a subpopulation of neural cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15136145", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The Drosophila melanogaster genes, ladybird early (lbe) and ladybird late (lbl), encode transcriptional regulators, which play an important role in neurogenesis, myogenesis and cardiogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16378763", "endSection": "abstract" } ] }, { "body": "Should istiratumab be used for Pancreatic Cancer?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31912800" ], "ideal_answer": [ "No. In a clinical trial Istiratumab failed to improve the efficacy of standard of care chemotherapy in metastatic pancreatic cancer patients." ], "exact_answer": "no", "type": "yesno", "id": "61fa9a60c9dfcb9c09000007", "snippets": [ { "offsetInBeginSection": 1862, "offsetInEndSection": 1963, "text": "CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31912800", "endSection": "abstract" }, { "offsetInBeginSection": 1330, "offsetInEndSection": 1595, "text": "In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR)\u00a0= 1.88, P\u00a0= 0.027]. In the high IGF-1/HRG+ subgroup (n\u00a0= 44), median PFS was 4.1 and 7.3 months, respectively (HR\u00a0= 1.39, P\u00a0= 0.42).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31912800", "endSection": "abstract" } ] }, { "body": "When is the protein OAS1 activated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34108012", "http://www.ncbi.nlm.nih.gov/pubmed/34082434", "http://www.ncbi.nlm.nih.gov/pubmed/33307546", "http://www.ncbi.nlm.nih.gov/pubmed/34826092", "http://www.ncbi.nlm.nih.gov/pubmed/34873989" ], "ideal_answer": [ "OAS1 is a IFN-stimulated gene. Antiviral response." ], "exact_answer": [ "IFN stimulated for antiviral resonse." ], "type": "factoid", "id": "62587803e764a5320400002b", "snippets": [ { "offsetInBeginSection": 617, "offsetInEndSection": 687, "text": " encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33307546", "endSection": "abstract" }, { "offsetInBeginSection": 1804, "offsetInEndSection": 1870, "text": "interferon-stimulating genes (ISG15, IFI6, IFI27, IFI44, and OAS1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34108012", "endSection": "abstract" }, { "offsetInBeginSection": 651, "offsetInEndSection": 705, "text": "IFN-stimulated genes (ISGs: ISG56, OAS1, MxA, and Mx2)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34082434", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5As, which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34826092", "endSection": "abstract" }, { "offsetInBeginSection": 437, "offsetInEndSection": 486, "text": "OAS1 gene in activation of innate immune response", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34873989", "endSection": "abstract" } ] }, { "body": "Does Amblyopia affect the eye?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19195640", "http://www.ncbi.nlm.nih.gov/pubmed/23894908", "http://www.ncbi.nlm.nih.gov/pubmed/14680777", "http://www.ncbi.nlm.nih.gov/pubmed/20671288", "http://www.ncbi.nlm.nih.gov/pubmed/12913328", "http://www.ncbi.nlm.nih.gov/pubmed/31453915", "http://www.ncbi.nlm.nih.gov/pubmed/29905124", "http://www.ncbi.nlm.nih.gov/pubmed/29687838", "http://www.ncbi.nlm.nih.gov/pubmed/25637856", "http://www.ncbi.nlm.nih.gov/pubmed/22789926", "http://www.ncbi.nlm.nih.gov/pubmed/20826682", "http://www.ncbi.nlm.nih.gov/pubmed/20922043", "http://www.ncbi.nlm.nih.gov/pubmed/24386790", "http://www.ncbi.nlm.nih.gov/pubmed/3278568", "http://www.ncbi.nlm.nih.gov/pubmed/21061879", "http://www.ncbi.nlm.nih.gov/pubmed/457357", "http://www.ncbi.nlm.nih.gov/pubmed/19146342", "http://www.ncbi.nlm.nih.gov/pubmed/31833253", "http://www.ncbi.nlm.nih.gov/pubmed/21870913", "http://www.ncbi.nlm.nih.gov/pubmed/22883843", "http://www.ncbi.nlm.nih.gov/pubmed/7799459", "http://www.ncbi.nlm.nih.gov/pubmed/31712066", "http://www.ncbi.nlm.nih.gov/pubmed/34499336", "http://www.ncbi.nlm.nih.gov/pubmed/6853107", "http://www.ncbi.nlm.nih.gov/pubmed/31852024", "http://www.ncbi.nlm.nih.gov/pubmed/34682200", "http://www.ncbi.nlm.nih.gov/pubmed/31281344", "http://www.ncbi.nlm.nih.gov/pubmed/2062534", "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "http://www.ncbi.nlm.nih.gov/pubmed/26917086", "http://www.ncbi.nlm.nih.gov/pubmed/34679448", "http://www.ncbi.nlm.nih.gov/pubmed/31161888", "http://www.ncbi.nlm.nih.gov/pubmed/18025648", "http://www.ncbi.nlm.nih.gov/pubmed/9698332" ], "ideal_answer": [ "Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to process inputs from one eye and over time favors the other eye. It results in decreased vision in an eye that otherwise typically appears normal" ], "exact_answer": "yes", "type": "yesno", "id": "605b9c2a94d57fd879000035", "snippets": [ { "offsetInBeginSection": 165, "offsetInEndSection": 424, "text": "The main goal of our study is to assess the effect of transcranial magnetic stimulation, specifically theta burst stimulation (TBS), in a group of amblyopic volunteers measuring several visual parameters: visual acuity, suppressive imbalance, and stereoacuity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31453915", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 419, "text": "This study was undertaken to determine if optometrists in Ghana screen, diagnose and manage paediatric ocular conditions (for example, strabismus, amblyopia), and further assessed if optometrists in Ghana have the requisite paediatric instrumentation in their practices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31852024", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 78, "text": "Many bilateral amblyopia patients have asymmetric visual acuity (VA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31712066", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 780, "text": "LTS: In patients with persistent amblyopia and in those with recovered amblyopia, the affected eyes were significantly more hyperopic than the fellow eyes. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20922043", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 619, "text": "e RNFLT was compared between the affected and fellow eyes in patients with persistent amblyopia and in those with recovered amblyopia, and between the amblyopic eyes of patients with persistent amblyopia and the previously amblyopic eyes of patients with recovered amblyopia.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20922043", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 395, "text": "We compared the optic nerve head topography and retinal nerve fiber layer (RNFL) thickness of the strabismic and anisometropic amblyopic eyes with the normal fellow eyes and age-matched controls and concluded that, although amblyopia is a functional visual loss, RNFL thickness and optic nerve head topographic changes in strabismic and anisometropic amblyopic eyes may be affected by amblyopia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18025648", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 389, "text": "ODS: Four consecutive infants between 7 and 19 months of age with unilateral periocular vascular lesions that intermittently obstructed vision in the affected eye and no clinical evidence of amblyopia were evaluated. No ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19195640", "endSection": "abstract" }, { "offsetInBeginSection": 265, "offsetInEndSection": 458, "text": "Histologic study of the LGNs from a patient with ophthalmologically confirmed anisometropic amblyopia shows a decrease of cell sizes in the parvocellular layers innervated by the amblyopic eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6853107", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1268, "text": "S: Neutral density filters affect eyes with strabismic amblyopia differently than they do non-amblyopic eyes. A signifi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22883843", "endSection": "abstract" }, { "offsetInBeginSection": 432, "offsetInEndSection": 654, "text": "Together with recent advances in our theoretical understanding of amblyopia and technological advances in amblyopia treatment, we anticipate improved visual outcomes for children affected by this very common eye condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34499336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "OBJECTIVE: Amblyopia or lazy eye is a common visual problem affecting children that cannot correct with lenses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29687838", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Experimental amblyopia in animal models causes a reduction of cell sizes in lateral geniculate nucleus (LGN) laminae connected with the amblyopic eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6853107", "endSection": "abstract" }, { "offsetInBeginSection": 554, "offsetInEndSection": 671, "text": "Amblyopia cannot be cured by treating the cause alone; the weaker eye must be made stronger in order to see normally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7799459", "endSection": "abstract" }, { "offsetInBeginSection": 429, "offsetInEndSection": 492, "text": "To correct amblyopia, a child must be made to use the weak eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7799459", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1106, "text": "Similarly, decreased activation of the LGN as well as the visual cortex by the affected eye was demonstrated in the patient with anisometropic amblyopia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12913328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "Amblyopia is a developmental disorder that affects the spatial vision of one or both eyes in the absence of an obvious organic cause; it is associated with a history of abnormal visual experience during childhood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29905124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Amblyopia is defined as the reduction of best-corrected visual acuity of one or both eyes caused by conditions that affect normal visual development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31833253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Amblyopia is a reduced best-corrected visual acuity of one or both eyes that cannot be attributed to a structural abnormality; it is a functional reduction in the vision of an eye caused by disuse during a critical period of visual development", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34682200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Amblyopia is defined as reduced and uncorrectable vision in a structurally normal eye", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21061879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Amblyopia or \"lazy eye\" represents a disorder of the visual system characterized by poor vision in an eye that is otherwise physically normal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24386790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Amblyopia is a common visual disorder that results in a spatial acuity deficit in the affected eye", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21870913", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 418, "text": "Amblyopia is a common deficit in spatial vision that could be based on either unreliable local estimates of image structure, irregularities in global image integration or a combination of errors at both these stages.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14680777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Amblyopia is a disorder of visual acuity in one eye, thought to arise from suppression by the other eye during development of the visual cortex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19146342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Amblyopia is characterised by decrease in vision in one or both eyes as a result of processing defect in the visual pathways of the brain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23894908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917086", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Amblyopia, commonly known as \"lazy eye,\" is a frequent but preventable cause of decreased vision", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3278568", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1187, "text": "Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 742, "text": "Therefore, the aim of this review paper is to provide a comprehensive review of current knowledge about the effects of amblyopia on eye movements, upper limb reaching and grasping movements, as well as balance and gait", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31281344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Atropine occlusion in the treatment of strabismic amblyopia and its effect upon the non-amblyopic eye.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2062534", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Amblyopia is the most common cause of monocular visual impairment in children, with a prevalence of 2-3%", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34499336", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Amblyopia is a neurodevelopmental disorder of the visual system, as a result of discordant visual experience during infancy or early childhood", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31161888", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 425, "text": "By its nature, however, amblyopia has an adverse effect on the development of a binocular visual system and the interactions between signals from two eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Unilateral Amblyopia Affects Two Eyes: Fellow Eye Deficits in Amblyopia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "PURPOSE: Impairment of spatiotemporal visual processing is the hallmark of amblyopia, but its effects on eye movements during visuomotor tasks have rarely been", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20671288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 257, "text": "Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26917086", "endSection": "abstract" }, { "offsetInBeginSection": 1466, "offsetInEndSection": 1667, "text": "Further research targeted at exploring fellow eye deficits in amblyopia will provide us with a broader understanding of normal visual development and how amblyopia impacts the developing visual system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "abstract" }, { "offsetInBeginSection": 606, "offsetInEndSection": 777, "text": "While these fellow eye deficits have been noted, no overarching theory has been proposed to describe why and under what conditions the fellow eye is impacted by amblyopia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 1188, "text": "Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "abstract" }, { "offsetInBeginSection": 479, "offsetInEndSection": 645, "text": "In anisometropes, the amblyopic eye influenced a relatively small proportion of cortical neurons; in strabismics, the influence of the two eyes was more nearly equal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9698332", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 350, "text": "studied. Here the authors investigate how visual deficits in anisometropic amblyopia affect saccadic eye movements.METHODS: Thirteen patients with anisometropic amblyopia and 13 control subj", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20671288", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Unilateral amblyopia is a visual disorder that arises after selective disruption of visual input to one eye during critical periods of development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Amblyopia is a developmental disorder resulting in poor vision in one eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25637856", "endSection": "abstract" }, { "offsetInBeginSection": 148, "offsetInEndSection": 269, "text": "In the clinic, amblyopia is understood as poor visual acuity in an eye that was deprived of pattern vision early in life.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28346616", "endSection": "abstract" }, { "offsetInBeginSection": 63, "offsetInEndSection": 207, "text": "Ocular misalignment or unilateral blur often causes amblyopia, a disorder that has become a standard for understanding developmental plasticity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20826682", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Amblyopia is a developmental disorder of pattern vision.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9698332", "endSection": "abstract" }, { "offsetInBeginSection": 1538, "offsetInEndSection": 1628, "text": " amblyopia are associated with poor PS. PS of amblyopic and fellow eyes is differentially ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22789926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "The contrast sensitivity function of both eyes of subjects with functional amblyopia has been measured. A clinically significant difference was found between the amblyopic and the normal eye.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/457357", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 328, "text": "t appears that the functionally amblyopic eye takes more information from the peripheral parts of the stimulus than does the normal eye", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/457357", "endSection": "abstract" }, { "offsetInBeginSection": 95, "offsetInEndSection": 388, "text": "Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34679448", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the Lonsurf combination pill?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32801768", "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "http://www.ncbi.nlm.nih.gov/pubmed/31002008", "http://www.ncbi.nlm.nih.gov/pubmed/33468799", "http://www.ncbi.nlm.nih.gov/pubmed/28315543", "http://www.ncbi.nlm.nih.gov/pubmed/26609205", "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "http://www.ncbi.nlm.nih.gov/pubmed/34207352", "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "http://www.ncbi.nlm.nih.gov/pubmed/33294265", "http://www.ncbi.nlm.nih.gov/pubmed/34034550", "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "http://www.ncbi.nlm.nih.gov/pubmed/27568360", "http://www.ncbi.nlm.nih.gov/pubmed/32891715" ], "ideal_answer": [ "Lonsurf is an oral fixed dose combination of trifluridine and tipiracil that is used for cancer treatment." ], "exact_answer": [ [ "trifluridine" ], [ "tipiracil" ] ], "type": "list", "id": "61fbc1acc9dfcb9c0900000d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "TAGS trial revealed the efficacy and safety of trifluridine/tipiracil(Lonsurf\u00ae)treatment in patients with metastatic gastric cancer following gastrectomy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33468799", "endSection": "abstract" }, { "offsetInBeginSection": 1876, "offsetInEndSection": 2101, "text": "What is already known TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31002008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Trifluridine/tipiracil (Lonsurf\u00ae) is a fixed-dose combination tablet comprising trifluridine, an antineoplastic nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "Trifluridine/tipiracil or TAS-102 (Taiho Oncology, Lonsurf\u00ae, Princeton, NJ, USA) is a combination tablet of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor, in a 1:0.5 molar ratio.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32801768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "TAS-102/Lonsurf is a new oral anti-tumor drug consisting of trifluridine and tipiracil in a 1:0.5 molar ratio. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33294265", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 352, "text": "TAS-102 (Lonsurf) is an oral fluoropyrimidine that is formed by the combination of 2 active drugs: trifluridine (a nucleoside analog) and tipiracil hydrochloride (a thymidine phosphorylase inhibitor).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Trifluridine/tipiracil or TAS-102 (Taiho Oncology, Lonsurf\u00ae, Princeton, NJ, USA) is a combination tablet of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor, in a 1:0.5 molar ratio. This drug was first a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32801768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Trifluridine/tipiracil (Lonsurf\u00ae) is a fixed-dose combination tablet comprising trifluridine, an antineoplastic nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor. Tr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31489588", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 358, "text": "S-102 (Lonsurf) is an oral fluoropyrimidine that is formed by the combination of 2 active drugs: trifluridine (a nucleoside analog) and tipiracil hydrochloride (a thymidine phosphorylase inhibitor). This ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27431756", "endSection": "abstract" }, { "offsetInBeginSection": 1848, "offsetInEndSection": 2077, "text": " two Asian efficacy trials. What is already known TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic co", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31002008", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Trifluridine/tipiracil or TAS-102 (Taiho Oncology, Lonsurf\u00ae, Princeton, NJ, USA) is a combination tablet of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor, in a 1:0.5 molar ratio. This dr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32801768", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf\u00ae tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "TAS-102/Lonsurf is a new oral anti-tumor drug consisting of trifluridine and tipiracil in a 1:0.5 molar ratio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33294265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Trifluridine/tipiracil (Lonsurf(\u00ae)) is a novel, orally active, antimetabolite agent comprised of trifluridine, a thymidine-based nucleoside analogue, and tipiracil, a potent thymidine phosphorylase inhibitor. Triflur", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27568360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Trifluridine/tipiracil (FTD/TPI; marketed as Lonsurf\u00ae) has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32891715", "endSection": "abstract" }, { "offsetInBeginSection": 132, "offsetInEndSection": 368, "text": "erapy. These AEs may affect patient adherence, particularly with completely oral regimens, such as trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), an antimetabolite agent for patients with mCRC refractory or intolerant to standard therapies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28315543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "TAS-102/Lonsurf is a new oral anti-tumor drug consisting of trifluridine and tipiracil in a 1:0", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33294265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf\u00ae tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34034550", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 359, "text": "BACKGROUND: Trifluridine/tipiracil (TAS-102, Lonsurf\u00ae), a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine, FTD) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride, TPI) presents a new treatment option for metastatic colorectal cancer (mCRC) patients refractory or intolerant to standar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30445951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf\u00ae tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26197742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "TAS-102/Lonsurf is a new oral anti-tumor drug consisting of trifluridine and tipiracil in a 1:0.5 molar ratio.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33294265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Trifluridine/tipiracil (FTD/TPI; marketed as Lonsurf\u00ae) has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32891715", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8\u2009months in metastatic colorectal cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34034550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "TAGS trial revealed the efficacy and safety of trifluridine/tipiracil(Lonsurf\u00ae)treatment in patients with metastatic gastric cancer following gastrectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33468799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "In the UK, Trifluridine-tipiracil (Lonsurf) is used to treat metastatic colorectal cancer in the third-line setting, after prior exposure to fluoropyrimidine-based regimes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34207352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 283, "text": "Evolocumab (Repatha) for patients with hypercholesterolemia whose condition has not been controlled by statins and other therapies; trifluridine/tipiracil (Lonsurf) for metastatic colorectal cancer; and blood coagulation factor VIII (Nuwiq) for adults and children with hemophilia A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26609205", "endSection": "abstract" } ] }, { "body": "What is the correlation of Cathepsin L and COVID-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34527703", "http://www.ncbi.nlm.nih.gov/pubmed/34575910", "http://www.ncbi.nlm.nih.gov/pubmed/34807310" ], "ideal_answer": [ "Cathepsin L (CTSL) is a kind of the SARS-entry-associated CoV-2's proteases, which plays a key role in the virus's entry into the cell and subsequent infection" ], "type": "summary", "id": "62587e14e764a5320400002c", "snippets": [ { "offsetInBeginSection": 437, "offsetInEndSection": 578, "text": "We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34575910", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 490, "text": "Based on the accessibility of the cellular proteases needed for SARS-S activation, SARS-CoV-2 entrance and activation can be mediated by endosomal (such as cathepsin L) and non-endosomal pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34527703", "endSection": "abstract" }, { "offsetInBeginSection": 13, "offsetInEndSection": 174, "text": " Cathepsin L (CTSL) is a kind of the SARS-entry-associated CoV-2's proteases, which plays a key role in the virus's entry into the cell and subsequent infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34807310", "endSection": "abstract" } ] }, { "body": "Is autism thought to be related to the Arginine Vasopressin Peptide (AVP)?", "_type": "yesno", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/15098001", "http://www.ncbi.nlm.nih.gov/pubmed/28283809", "http://www.ncbi.nlm.nih.gov/pubmed/32650534", "http://www.ncbi.nlm.nih.gov/pubmed/32341146", "http://www.ncbi.nlm.nih.gov/pubmed/31043522", "http://www.ncbi.nlm.nih.gov/pubmed/28258508", "http://www.ncbi.nlm.nih.gov/pubmed/26200852", "http://www.ncbi.nlm.nih.gov/pubmed/31571878", "http://www.ncbi.nlm.nih.gov/pubmed/21150165", "http://www.ncbi.nlm.nih.gov/pubmed/23413037", "http://www.ncbi.nlm.nih.gov/pubmed/27974283", "http://www.ncbi.nlm.nih.gov/pubmed/21453499", "http://www.ncbi.nlm.nih.gov/pubmed/17174726" ], "_body": "Is autism thought to be related to the gene for vasopressin?", "ideal_answer": [ "Differences in vasopressin levels in individuals suffering from the autism spectrum disorders have been demonstrated.", "Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD." ], "exact_answer": "yes", "type": "yesno", "id": "603bc2b61cb411341a00015b", "snippets": [ { "offsetInBeginSection": 202, "offsetInEndSection": 389, "text": "However, we recently found that cerebrospinal fluid (CSF) concentration of the \"social\" neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32341146", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 588, "text": "A large number of controlled trials demonstrated that exogenous oxytocin or arginine-vasopressin administration can mitigate social behavior impairment in ASD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32650534", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 427, "text": "An accumulating body of evidence indicates a tight relationship between the endocrine system and abnormal social behavior. Two evolutionarily conserved hypothalamic peptides, oxytocin and arginine-vasopressin, because of their extensively documented function in supporting and regulating affiliative and socio-emotional responses, have attracted great interest for their critical implications for autism spectrum disorders (ASD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32650534", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 351, "text": "Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31043522", "endSection": "abstract" }, { "offsetInBeginSection": 1596, "offsetInEndSection": 1707, "text": "These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31043522", "endSection": "abstract" }, { "offsetInBeginSection": 534, "offsetInEndSection": 687, "text": "The aim of this study was a systematic review of previous studies regarding the differences in OXT and vasopressin levels in ASD and neurotypical persons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31571878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Differences in oxytocin and vasopressin levels in individuals suffering from the autism spectrum disorders vs general population - a systematic review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31571878", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "The contribution of oxytocin and vasopressin to mammalian social behavior: potential role in autism spectrum disorder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21150165", "endSection": "title" }, { "offsetInBeginSection": 178, "offsetInEndSection": 507, "text": "Although the mechanisms underlying its etiology and manifestations are poorly understood, several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin (OXT) and arginine-vasopressin (AVP), as these neuropeptides modulate various aspects of mammalian social behavior.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28283809", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 356, "text": "linical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31043522", "endSection": "abstract" }, { "offsetInBeginSection": 576, "offsetInEndSection": 687, "text": "Previous results suggest that OXT and arginine vasopressin (AVP) may play a role in the etiopathogenesis of ASD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27974283", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "There has been intensified interest in the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in autism spectrum disorders (ASD) given their role in affiliative and social behavior in animals, positive results of treatment studies using OT, and findings that genetic polymorphisms in the AVP-OT pathway are present in individuals with ASD", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23413037", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "BACKGROUND: Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21453499", "endSection": "abstract" }, { "offsetInBeginSection": 186, "offsetInEndSection": 350, "text": "Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31043522", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "There has been intensified interest in the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in autism spectrum disorders (ASD) given their role in affiliative and social behavior in animals, positive results of treatment studies using OT, and findings that genetic polymorphisms in the AVP-OT pathway are present in individuals with ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23413037", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 334, "text": "We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26200852", "endSection": "abstract" }, { "offsetInBeginSection": 1051, "offsetInEndSection": 1250, "text": "Given the emerging biological, animal model, and now genetic data, AVPR1a and genes in the AVP system remain strong candidates for involvement in autism susceptibility and deserve continued scrutiny.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15098001", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 374, "text": "The behavioral effects of AVP are mediated through the AVP receptor 1a (AVPR1a), making the AVPR1a gene a reasonable candidate for autism susceptibility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15098001", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Dysfunction of brain-derived arginine-vasopressin (AVP) systems may be involved in the etiology of autism spectrum disorder (ASD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28258508", "endSection": "abstract" }, { "offsetInBeginSection": 1557, "offsetInEndSection": 1695, "text": "These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28258508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26200852", "endSection": "title" }, { "offsetInBeginSection": 1554, "offsetInEndSection": 1698, "text": "These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26200852", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Genes Related to Oxytocin and Arginine-Vasopressin Pathways: Associations with Autism Spectrum Disorders.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28283809", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "BACKGROUND: Dysregulation of the vasopressin (AVP) system has been implicated in the pathogenesis of autistic spectrum dis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17174726", "endSection": "abstract" } ] }, { "body": "Are there any tools that could predict protein structure considering amino acid sequence?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31063641", "http://www.ncbi.nlm.nih.gov/pubmed/33999203", "http://www.ncbi.nlm.nih.gov/pubmed/15980586", "http://www.ncbi.nlm.nih.gov/pubmed/31251384", "http://www.ncbi.nlm.nih.gov/pubmed/19433514", "http://www.ncbi.nlm.nih.gov/pubmed/17888742", "http://www.ncbi.nlm.nih.gov/pubmed/21780007", "http://www.ncbi.nlm.nih.gov/pubmed/34265844", "http://www.ncbi.nlm.nih.gov/pubmed/19046975", "http://www.ncbi.nlm.nih.gov/pubmed/18463136", "http://www.ncbi.nlm.nih.gov/pubmed/31388850", "http://www.ncbi.nlm.nih.gov/pubmed/20066664", "http://www.ncbi.nlm.nih.gov/pubmed/23772049", "http://www.ncbi.nlm.nih.gov/pubmed/15215441", "http://www.ncbi.nlm.nih.gov/pubmed/15978619", "http://www.ncbi.nlm.nih.gov/pubmed/18757875", "http://www.ncbi.nlm.nih.gov/pubmed/26519323" ], "ideal_answer": [ "Yes. Tools such as Jpred, Jnet, Porter 4.0 and PSIPRED Workbench have been developed that predict protein structure based solely on its amino acid sequence, whereas the recently updated Jnet algorithm provides a three-state (alpha-helix, beta-strand and coil) prediction of secondary structure at an accuracy of 81.5%.", "AlphaFold, PredictProtein, PSIPRED, Jpred and Porter do all predict protein stucture from amino acid sequence." ], "exact_answer": [ [ "AlphaFold" ], [ "PredictProtein", "predictprotein" ], [ "PSIPRED", "PSIPRED Workbench" ], [ "Jpred", "jpred" ], [ "Porter", "PaleAle 4.0", "porter 4.0", "PaleAle" ], [ "Jnet", "jnet algorithm" ] ], "type": "list", "id": "6278dd6156bf9aee6f000012", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 114, "text": "PredictProtein (https://predictprotein.org) is a one-stop online resource for protein sequence analysis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33999203", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Jpred (http://www.compbio.dundee.ac.uk/jpred) is a secondary structure prediction server", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463136", "endSection": "abstract" }, { "offsetInBeginSection": 203, "offsetInEndSection": 355, "text": "The recently updated Jnet algorithm provides a three-state (alpha-helix, beta-strand and coil) prediction of secondary structure at an accuracy of 81.5%", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18463136", "endSection": "abstract" }, { "offsetInBeginSection": 272, "offsetInEndSection": 371, "text": "Porter 4.0 and PaleAle 4.0. Porter 4.0 predicts secondary structure correctly for 82.2% of residues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23772049", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 685, "text": "Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34265844", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The PSIPRED Workbench is a web server offering a range of predictive methods", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31251384", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "PreSSAPro is a software, available to the scientific community as a free web service designed to provide predictions of secondary structures starting from the amino acid sequence of a given protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17888742", "endSection": "abstract" }, { "offsetInBeginSection": 214, "offsetInEndSection": 412, "text": "A detailed explanation is provided for the use of Distill, a suite of web servers for the prediction of protein structural features and the prediction of full-atom 3D models from a protein sequence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21780007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "PROSPECT-PSPP: an automatic computational pipeline for protein structure prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15215441", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "PREDICT-2ND: a tool for generalized protein local structure prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18757875", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "PaleAle 5.0: prediction of protein relative solvent accessibility by deep learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31388850", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "ProTarget: automatic prediction of protein structure novelty.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15980586", "endSection": "title" }, { "offsetInBeginSection": 687, "offsetInEndSection": 764, "text": "cutting-edge web-server method IntFOLD2-TS for tertiary structure prediction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26519323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Using PconsC4 and PconsFold2 to Predict Protein Structure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31063641", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Protein structure prediction enhanced with evolutionary diversity: SPEED.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20066664", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Protein secondary structure prediction using three neural networks and a segmental semi Markov model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19046975", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "PEP-FOLD: an online resource for de novo peptide structure prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19433514", "endSection": "title" } ] }, { "body": "Which proteins does p110\u03b1 interact with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24367658", "http://www.ncbi.nlm.nih.gov/pubmed/24229705", "http://www.ncbi.nlm.nih.gov/pubmed/34884613", "http://www.ncbi.nlm.nih.gov/pubmed/24229709", "http://www.ncbi.nlm.nih.gov/pubmed/23086038", "http://www.ncbi.nlm.nih.gov/pubmed/30683915", "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "http://www.ncbi.nlm.nih.gov/pubmed/25003191" ], "ideal_answer": [ "p110\u03b1 interacts with p85\u03b1 and RAS proteins.", "RAS interaction with PI3K p110\u03b1" ], "exact_answer": [ [ "p85\u03b1", "p85" ], [ "RAS", "ras" ] ], "type": "list", "id": "62793b1c56bf9aee6f00001e", "snippets": [ { "offsetInBeginSection": 63, "offsetInEndSection": 85, "text": "p110\u03b1-p85\u03b1 heterodimer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "endSection": "title" }, { "offsetInBeginSection": 691, "offsetInEndSection": 707, "text": "p110\u03b1-p85\u03b1 dimer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1226, "text": "p110\u03b1-p85\u03b1 interface", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 31, "text": "RAS interaction with PI3K p110\u03b1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003191", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 328, "text": "interaction between RAS and p110\u03b1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003191", "endSection": "abstract" }, { "offsetInBeginSection": 529, "offsetInEndSection": 569, "text": "functional interaction of RAS with p110\u03b1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003191", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 698, "text": "RAS and p110\u03b1 interaction", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003191", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1088, "text": "RAS interaction with PI3K p110\u03b1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25003191", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1169, "text": "PAQR3 interacts with the domain of p110\u03b1 involved in its binding with p85, the regulatory subunit of PI3K", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23086038", "endSection": "abstract" } ] }, { "body": "Which is the protein-membrane interface of the Cholesterol-regulated Start protein 4 protein (STARD4)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26168008" ], "ideal_answer": [ "L124 is the protein-membrane interface of the Cholesterol-regulated Start protein 4 protein (STARD4).", "Our results show that STARD4 interacts with anionic membranes through a surface-exposed basic patch and that introducing a mutation (L124D) into the Omega-1 (\u03a91) loop, which covers the sterol binding pocket, attenuates sterol transfer activity." ], "exact_answer": [ "L124", "Omega-1 (\u03a91) loop" ], "type": "factoid", "id": "6278ca4a56bf9aee6f00000c", "snippets": [ { "offsetInBeginSection": 750, "offsetInEndSection": 994, "text": "Our results show that STARD4 interacts with anionic membranes through a surface-exposed basic patch and that introducing a mutation (L124D) into the Omega-1 (\u03a91) loop, which covers the sterol binding pocket, attenuates sterol transfer activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26168008", "endSection": "abstract" }, { "offsetInBeginSection": 765, "offsetInEndSection": 1014, "text": "w that STARD4 interacts with anionic membranes through a surface-exposed basic patch and that introducing a mutation (L124D) into the Omega-1 (\u03a91) loop, which covers the sterol binding pocket, attenuates sterol transfer activity. To gain insight int", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26168008", "endSection": "abstract" } ] }, { "body": "What causes the \"worst headache\" of a patient's life?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17929738", "http://www.ncbi.nlm.nih.gov/pubmed/28434443", "http://www.ncbi.nlm.nih.gov/pubmed/27741994", "http://www.ncbi.nlm.nih.gov/pubmed/9737490", "http://www.ncbi.nlm.nih.gov/pubmed/22338211" ], "ideal_answer": [ "This is a classic description of a subarachnoid hemorrhage (SAH). The gold standard for the diagnostic evaluation of a SAH remains non-contrast head computed tomography (CT) followed by lumbar puncture if the CT is negative.", "Headache is the most common presenting symptom of subarachnoid hemorrhage (SAH), ranging from mild headache to the \"worst headache of my life\"", "Aneurysmal subarachnoid hemorrhage (SAH) is associated with a mortality of more than 30%. Acute, severe headache, typically described as the worst headache of the patient's life, and meningismus are the characteristic manifestations of SAH." ], "exact_answer": [ "Subarachnoid hemorrhage (SAH)", "Aneurysmal subarachnoid hemorrhage" ], "type": "factoid", "id": "627a875a56bf9aee6f000023", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 101, "text": "Aneurysmal subarachnoid hemorrhage (SAH) is associated with a mortality of more than 30%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28434443", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 710, "text": "Acute, severe headache, typically described as the worst headache of the patient's life, and meningismus are the characteristic manifestations of SAH. Computed tomog raphy (CT) reveals blood in the basal cisterns in the first 12 hours after SAH with approximately 95% sensitivity and specificity. If no blood is seen on CT, a lumbar puncture must be performed to confirm or rule out the diagnosis of SAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28434443", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 451, "text": "Aneurysmal subarachnoid hemorrhage (SAH) is a neurological emergency with high risk of neurological decline and death. Although the presentation of a thunderclap headache or the worst headache of a patient's life easily triggers the evaluation for SAH, subtle presentations are still missed. The gold standard for diagnostic evaluation of SAH remains noncontrast head computed tomography (CT) followed by lumbar puncture if the CT is negative for SAH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27741994", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 155, "text": "Headache is the most common presenting symptom of subarachnoid hemorrhage (SAH), ranging from mild headache to the \"worst headache of my life\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22338211", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Patients who survive an Aneurysmal Subarachnoid Haemorrhage or ASAH describe it as being the worst headache ever, multiplied one hundred-times over.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17929738", "endSection": "abstract" } ] }, { "body": "Which are the types of cancer that c-Myc is associated with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19174520", "http://www.ncbi.nlm.nih.gov/pubmed/20737197", "http://www.ncbi.nlm.nih.gov/pubmed/18190704", "http://www.ncbi.nlm.nih.gov/pubmed/20697349", "http://www.ncbi.nlm.nih.gov/pubmed/1493439", "http://www.ncbi.nlm.nih.gov/pubmed/28623290", "http://www.ncbi.nlm.nih.gov/pubmed/33390842", "http://www.ncbi.nlm.nih.gov/pubmed/28160502", "http://www.ncbi.nlm.nih.gov/pubmed/3332004", "http://www.ncbi.nlm.nih.gov/pubmed/3670047", "http://www.ncbi.nlm.nih.gov/pubmed/24646303", "http://www.ncbi.nlm.nih.gov/pubmed/30226440", "http://www.ncbi.nlm.nih.gov/pubmed/2227545", "http://www.ncbi.nlm.nih.gov/pubmed/29263157", "http://www.ncbi.nlm.nih.gov/pubmed/28741879", "http://www.ncbi.nlm.nih.gov/pubmed/30224636", "http://www.ncbi.nlm.nih.gov/pubmed/31144531", "http://www.ncbi.nlm.nih.gov/pubmed/26954716", "http://www.ncbi.nlm.nih.gov/pubmed/25306215", "http://www.ncbi.nlm.nih.gov/pubmed/8353142", "http://www.ncbi.nlm.nih.gov/pubmed/15929079" ], "ideal_answer": [ "The types of cancer that c-Myc is associates with are breast cancer, non-small-cell lung cancer and pancreatic ductal adenocarcinoma.", "c-Myc is known to be deregulated in a variety of tumors, including breast cancer, prostate cancer, non-small cell lung cancer (NSCLC), papillary thyroid cancer (PDA), ovarian cancer, cervical intraepithelial neoplasia, and gastric cancer." ], "exact_answer": [ [ "Breast cancer", "breast cancer" ], [ "Non-small-cell lung cancer", "NSCLC" ], [ "Pancreatic ductal adenocarcinoma", "pda" ] ], "type": "list", "id": "62755c2a56bf9aee6f000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "As a transcription factor and proto-oncogene, MYC is known to be deregulated in a variety of tumors, including breast cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33390842", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1244, "text": "a tumor suppressor role of miR-376a in NSCLC by targeting c-Myc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28741879", "endSection": "abstract" }, { "offsetInBeginSection": 1833, "offsetInEndSection": 1989, "text": "These results provide strong justification for eventual clinical evaluation of anti-Myc drugs as potential chemotherapeutic agents for the treatment of PDA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25306215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "CONTEXT: c-Myc plays a key role in glioma cancer stem cell ma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24646303", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. U", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28160502", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 752, "text": "or types exhibiting c-myc as a \"progressor\" gene include breast, colon, small cell lung carcinoma, as well as ovarian cancer, lymphomas, and squamous cell carcinomas. The c-myc on", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8353142", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28623290", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Pancreatic adenocarcinoma is a highly malignant cancer that often involves a deregulation of c-Myc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30224636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Background: c-Myc is overexpressed in different types of cancer, including thyroid cancer, and has been considered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30226440", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 738, "text": "The tumor types exhibiting c-myc as a \"progressor\" gene include breast, colon, small cell lung carcinoma, as well as ovarian cancer, lymphomas, and squamous cell carcinomas", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8353142", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 739, "text": "The tumor types exhibiting c-myc as a \"progressor\" gene include breast, colon, small cell lung carcinoma, as well as ovarian cancer, lymphomas, and squamous cell carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8353142", "endSection": "abstract" }, { "offsetInBeginSection": 876, "offsetInEndSection": 1155, "text": "Different types of c-myc involvement are associated with specific types of lymphoma: there are differences between endemic, sporadic and ileocecal Burkitt's lymphoma as well as between those and primary extranodal large cell lymphoma and large cell lymphoma which has progressed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1493439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "The association of c-myc rearrangements with specific types of human non-Hodgkin's lymphomas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1493439", "endSection": "title" }, { "offsetInBeginSection": 226, "offsetInEndSection": 576, "text": "In a large number of cases it was determined that amplified oncogenes occurred in 10 to 20% of tumors with the following specific associations: c-myc in adenocarcinomas, squamous carcinomas and sarcomas but not hematologic malignancies; c-erbB2 in adenocarcinomas, particularly breast cancers; c-erbB1 in squamous carcinomas; N-myc in neuroblastomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3670047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "The upregulation or mutation of C-MYC has been observed in gastric, colon, breast, and lung tumors and in Burkitt's lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20737197", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 548, "text": "The involvement of c-myc in mouse plasmacytomas and human Burkitt's lymphoma is well known: due to chromosomal translocation c-myc comes under the influence of regulatory elements of immunoglobulin genes, leading to increased expression of the gene and proliferation of the cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1493439", "endSection": "abstract" }, { "offsetInBeginSection": 577, "offsetInEndSection": 729, "text": "A small number of cases suggested other specific associations: amplified c-myb in breast cancers; amplified c-ras-Ha and c-ras-Ki in ovarian carcinomas.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3670047", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1150, "text": "In small cell lung cancer, high levels of myc gene expression are usually associated with gene amplification, and not uncommonly there is rearrangement of some of the amplified copies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3332004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26954716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26954716", "endSection": "title" }, { "offsetInBeginSection": 424, "offsetInEndSection": 639, "text": "Several lung cancers of both small cell and non-small cell type (including adeno- and squamous cell lung cancer) express the proto-oncogenes c-, N-, or L-myc, and in some cases more than one of these family members.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3332004", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "c-MYC Asn11Ser is associated with increased risk for familial breast cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15929079", "endSection": "title" } ] }, { "body": "Which pathways are involved in cellular senescence?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29608137", "http://www.ncbi.nlm.nih.gov/pubmed/33855023", "http://www.ncbi.nlm.nih.gov/pubmed/15743671" ], "ideal_answer": [ "Cellular senescence requires signal transduction, and the two most important signaling pathways are the P16Ink4a/Rb (retinoblastoma protein) pathway and the P19Arf/P53/P21Cip1 pathway, which interact but independently regulate the process of the cells cycle." ], "exact_answer": [ [ "Activation of the p53/p21 tumor suppressor pathway" ], [ "Activation of the p16/pRB tumor suppressor pathway" ] ], "type": "list", "id": "621e2b7a54ca071a71a3bf9c", "snippets": [ { "offsetInBeginSection": 935, "offsetInEndSection": 1103, "text": "The signaling pathways activated by these stresses are funneled to the p53 and Rb proteins, whose combined levels of activity determine whether cells enter senescence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15743671", "endSection": "abstract" }, { "offsetInBeginSection": 1242, "offsetInEndSection": 1366, "text": "Activation of the p53/p21WAF1/CIP1 and p16INK4A/pRB tumor suppressor pathways play a central role in regulating senescence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33855023", "endSection": "abstract" } ] }, { "body": "Which disease phenotype has the worst prognosis in Duchenne Muscular Dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34342696", "http://www.ncbi.nlm.nih.gov/pubmed/1865568", "http://www.ncbi.nlm.nih.gov/pubmed/15637982", "http://www.ncbi.nlm.nih.gov/pubmed/21178099", "http://www.ncbi.nlm.nih.gov/pubmed/32791185", "http://www.ncbi.nlm.nih.gov/pubmed/20098710" ], "ideal_answer": [ "A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found. In particular, improvements in the correlation of FSIQ with mutation location were identified when a new classification system for mutations affecting the Dp140 isoform was implemented.", " A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found. In particular, improvements in the correlation of FSIQ with mutation location were identified when a new classification system for mutations affecting the Dp140 isoform was implemented.", "Dp140 isoform is related to increased risk of cognitive impairment and thus worse prognosis.", "A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found." ], "exact_answer": [ "Dp140 isoform" ], "type": "factoid", "id": "6278dfe956bf9aee6f000016", "snippets": [ { "offsetInBeginSection": 1039, "offsetInEndSection": 1344, "text": " A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found. In particular, improvements in the correlation of FSIQ with mutation location were identified when a new classification system for mutations affecting the Dp140 isoform was implemented.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20098710", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "The ACTN3 577XX Null Genotype Is Associated with Low Left Ventricular Dilation-Free Survival Rate in Patients with Duchenne Muscular Dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32791185", "endSection": "title" }, { "offsetInBeginSection": 1046, "offsetInEndSection": 1192, "text": "These results suggest that patients with Duchenne muscular dystrophy with defective cDMD have more severe disease than those without cDMD deficit.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1865568", "endSection": "abstract" }, { "offsetInBeginSection": 1118, "offsetInEndSection": 1401, "text": "Osteopontin genotype is a genetic modifier of disease severity in Duchenne dystrophy. Inclusion of genotype data as a covariate or in inclusion criteria in DMD clinical trials would reduce intersubject variance, and increase sensitivity of the trials, particularly in older subjects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21178099", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21178099", "endSection": "title" } ] }, { "body": "What links developmental pathways to ALS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31233613", "http://www.ncbi.nlm.nih.gov/pubmed/20832291", "http://www.ncbi.nlm.nih.gov/pubmed/32236823", "http://www.ncbi.nlm.nih.gov/pubmed/34599308", "http://www.ncbi.nlm.nih.gov/pubmed/30524706", "http://www.ncbi.nlm.nih.gov/pubmed/33835400", "http://www.ncbi.nlm.nih.gov/pubmed/31176720", "http://www.ncbi.nlm.nih.gov/pubmed/27428653" ], "ideal_answer": [ "A direct link between developmental pathways and ALS is not described. However, cytoskeletal proteins such as KIF5A are implicated in ALS, and the cytoskeletal protein N-cadherin is involved in plasticity of the cerebral cortex. Development depends on connections of the sympathetic nervous system, involving mechanisms such as axon growth, neuron survival, and dendrite growth. BACE1, which is involved in Alzheimer's disease, is also implicated in axonal regeneration." ], "type": "summary", "id": "6273a2cae764a53204000046", "snippets": [ { "offsetInBeginSection": 441, "offsetInEndSection": 796, "text": "Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599308", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1101, "text": "pharmacological BACE inhibition accelerates peripheral axon regeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32236823", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 483, "text": "opmental signaling pathways including WNT, MAPK and BMP/TGF-\u03b2 signaling play important roles in the formation and growth of the Drosophila NMJ. Studies of t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20832291", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 512, "text": "In developing an explanation for the onset of ALS, it remains a consideration that ALS has its origins in neonatal derangement of the \u03b3-aminobutyric acid (GABA)-ergic system, with delayed conversion from excitatory to mature inhibitory GABA and impaired excitation/inhibition balance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31233613", "endSection": "abstract" }, { "offsetInBeginSection": 1515, "offsetInEndSection": 1834, "text": " (STAT3, HOXD11, HES7, GLI1). We identified 77 ALS-associated genes with expression significantly altered by GM6 treatment (FDR\u2009<\u20090.10), which were known to function in neurogenesis, axon guidance and the intrinsic apoptosis pathway.Conclusions: Our findings support the hypothesis that GM6 acts through developmental-s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30524706", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27428653", "endSection": "title" }, { "offsetInBeginSection": 416, "offsetInEndSection": 581, "text": "Developmental morphogens, such as the Wnt family, regulate numerous features of neuronal physiology in the adult brain and have been implicated in neurodegeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31176720", "endSection": "abstract" } ] }, { "body": "Is thalidomide used as an immunomodulatory drug nowadays?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29920472", "http://www.ncbi.nlm.nih.gov/pubmed/28571559", "http://www.ncbi.nlm.nih.gov/pubmed/17168659", "http://www.ncbi.nlm.nih.gov/pubmed/31187860", "http://www.ncbi.nlm.nih.gov/pubmed/1605898", "http://www.ncbi.nlm.nih.gov/pubmed/28154372", "http://www.ncbi.nlm.nih.gov/pubmed/17369076", "http://www.ncbi.nlm.nih.gov/pubmed/11734114", "http://www.ncbi.nlm.nih.gov/pubmed/12803319", "http://www.ncbi.nlm.nih.gov/pubmed/20223727", "http://www.ncbi.nlm.nih.gov/pubmed/16305990", "http://www.ncbi.nlm.nih.gov/pubmed/20617746", "http://www.ncbi.nlm.nih.gov/pubmed/29285050", "http://www.ncbi.nlm.nih.gov/pubmed/12190008", "http://www.ncbi.nlm.nih.gov/pubmed/12789488", "http://www.ncbi.nlm.nih.gov/pubmed/22233815", "http://www.ncbi.nlm.nih.gov/pubmed/21048383", "http://www.ncbi.nlm.nih.gov/pubmed/15709921", "http://www.ncbi.nlm.nih.gov/pubmed/15718159", "http://www.ncbi.nlm.nih.gov/pubmed/12412207", "http://www.ncbi.nlm.nih.gov/pubmed/15327481" ], "ideal_answer": [ "Yes.", "Nowadays, thalidomide is being used as an immunomodulatory drug." ], "exact_answer": "yes", "type": "yesno", "id": "6278da4456bf9aee6f00000f", "snippets": [ { "offsetInBeginSection": 139, "offsetInEndSection": 322, "text": "Potential immunomodulatory, antiinflammatory, anti-angiogenic and sedative properties make thalidomide a good candidate for the treatment of several diseases such as multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28571559", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 520, "text": "In 1990s, however, thalidomide received attention due to the discovery of its anticancer potential derived from antiangiogenic and immunomodulatory activities, and its therapeutic effect on myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31187860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Thalidomide is an immunomodulatory agent; although its mechanisms of action are not fully understood, many authors have described its anti-inflammatory and immunosuppressive properties", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12412207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "Thalidomide has antiangiogenic and immunomodulatory properties and has recently been used in the management of human malignancies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15709921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "After nearly decades of extinction as a sedative and antiemetic, thalidomide reemerged as the parent compound of a novel and promising class of therapeutics termed the immunomodulatory drugs (IMiDs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16305990", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Thalidomide has antiangiogenic and immunomodulatory properties and has recently been used in the management of human malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15709921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Thalidomide is a drug that, since its development, has made history in the world of medicine--having been withdrawn and now has returned with a boom as an anticancer and immunomodulatory drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22233815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21048383", "endSection": "abstract" }, { "offsetInBeginSection": 94, "offsetInEndSection": 211, "text": "Thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11734114", "endSection": "abstract" }, { "offsetInBeginSection": 1093, "offsetInEndSection": 1259, "text": "Only in the last several years has thalidomide been aggressively investigated for its antiangiogenic potential and immunomodulatory properties in various tumor types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11734114", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "After nearly decades of extinction as a sedative and antiemetic, thalidomide reemerged as the parent compound of a novel and promising class of therapeutics termed the immunomodulatory drugs (IMiDs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16305990", "endSection": "abstract" }, { "offsetInBeginSection": 884, "offsetInEndSection": 1014, "text": "In the present review an attempt is made to highlight the immunomodulatory action of thalidomide in various pathologic conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22233815", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Thalidomide and its immunomodulatory analogues have numerous effects on the body's immune system, including potential anti-cancer and anti-inflammatory activities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15718159", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Thalidomide is an immunomodulatory agent; although its mechanisms of action are not fully understood, many authors have described its anti-inflammatory and immunosuppressive properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12412207", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Thalidomide (Thal) has antiangiogenic and immunomodulatory activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17168659", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases;", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28154372", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 542, "text": "The immunomodulatory agents thalidomide and lenalidomide and the proteasome inhibitor bortezomib are now routine components of MM therapy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20223727", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15327481", "endSection": "abstract" }, { "offsetInBeginSection": 188, "offsetInEndSection": 304, "text": " Its immunological effects were known already from earlier studies. Nowadays its use is accepted in myeloma therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20617746", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 502, "text": "Therapeutics that have proven to be highly effective include the immunomodulatory drug thalidomide and its newer analogs, lenalidomide and pomalidomide, as well as the proteasome inhibitors bortezomib and carfilzomib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29920472", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 328, "text": "As immunomodulatory drugs, thalidomide and its analogues have been used to effectively treat various diseases", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29285050", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 277, "text": "Its effectiveness in the clinic has been ascribed to wide-ranging properties, including anti-TNF-alpha, T-cell costimulatory and antiangiogenic activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12803319", "endSection": "abstract" }, { "offsetInBeginSection": 196, "offsetInEndSection": 402, "text": "Thalidomide has various immunomodulatory effects. Thalidomide inhibits TNF alpha production, has T-cell costimulatory properties and modulates the expression of cell surface molecules on leukocytes in vivo.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12190008", "endSection": "abstract" }, { "offsetInBeginSection": 23, "offsetInEndSection": 324, "text": " thalidomide has been a target of active investigation in both malignant and inflammatory conditions. Although initially developed for its sedative properties, decades of investigation have identified a multitude of biological effects that led to its classification as an immunomodulatory drug (IMiD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17369076", "endSection": "abstract" }, { "offsetInBeginSection": 503, "offsetInEndSection": 695, "text": "The mechanism of action of thalidomide is probably based on its immunomodulatory effect, namely the suppression of production of tumor necrosis factor alpha and the modulation of interleukins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12789488", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 343, "text": "This effect is probably due to a direct influence on the immune system", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1605898", "endSection": "abstract" } ] }, { "body": "Does p85\u03b1 homodimerize?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26475863", "http://www.ncbi.nlm.nih.gov/pubmed/21984976", "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "http://www.ncbi.nlm.nih.gov/pubmed/33127913" ], "ideal_answer": [ "p110\u03b1-free p85\u03b1 homodimerizes", "Yew, p85\u03b1 forms homodimers" ], "exact_answer": "yes", "type": "yesno", "id": "6278d0a756bf9aee6f00000e", "snippets": [ { "offsetInBeginSection": 241, "offsetInEndSection": 259, "text": "homodimerized p85\u03b1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 348, "text": "p110\u03b1-free p85\u03b1 homodimerizes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 526, "text": "homodimeric but not monomeric p85\u03b1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "endSection": "abstract" } ] }, { "body": "Which are the components that evaluate druglikeness?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11300855", "http://www.ncbi.nlm.nih.gov/pubmed/26771590", "http://www.ncbi.nlm.nih.gov/pubmed/21480669", "http://www.ncbi.nlm.nih.gov/pubmed/21142079", "http://www.ncbi.nlm.nih.gov/pubmed/33217892", "http://www.ncbi.nlm.nih.gov/pubmed/31817628", "http://www.ncbi.nlm.nih.gov/pubmed/11259830", "http://www.ncbi.nlm.nih.gov/pubmed/22778837" ], "ideal_answer": [ "Lipinski's rule states that, in general, an orally active drug has no more than one violation of the following criteria:\nNo more than 5 hydrogen bond donors (the total number of nitrogen\u2013hydrogen and oxygen\u2013hydrogen bonds)\nNo more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms)\nA molecular mass less than 500 daltons\nAn octanol-water partition coefficient (log P) that does not exceed 5", "In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP > 4.15)" ], "exact_answer": [ [ "No more than 5 hydrogen bond donors", "H-bond donors" ], [ "No more than 10 hydrogen bond acceptors", "H-bond acceptors" ], [ "A molecular mass less than 500 daltons", "molecular weight", "MWT" ], [ "An octanol-water partition coefficient (log P) that does not exceed 5", "MlogP", "CLogP" ] ], "type": "list", "id": "6278c73756bf9aee6f00000b", "snippets": [ { "offsetInBeginSection": 135, "offsetInEndSection": 414, "text": "In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP > 4.15).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11259830", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 623, "text": "anulocytic asthma. Initially, in silico studies of biseugenol showed good predictions for drug-likeness, with adherence to Lipinski's rules of five (RO5), good Absorption, Distribution, Metabolism and Excretion (ADME) properties and no alerts for Pan-Assay Interference Compounds (PAINS), indicating adequate adherence to perform in viv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33217892", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 1084, "text": "\"Druglikeness\" was examined using an eight-test panel in vitro, i.e., a parallel artificial membrane permeability assay (PAMPA), and Caco-2 permeability-, P-glycoprotein (Pgp) affinity-, plasma protein binding-, metabolic stability- and drug-drug interaction-assays, as well as mutagenicity- and HepG2-hepatotoxicity risk tests.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31817628", "endSection": "abstract" }, { "offsetInBeginSection": 596, "offsetInEndSection": 911, "text": "This classification also enabled an analysis of atom type and physicochemical property distributions (for calculated log P, molar refractivity, molecular weight, total atom count, and ATD) of drug, lead, and nondrug databases, a reassessment of the Ro5 (Rule of Five) and GVW (Ghose\u2212Viswanadhan\u2212Wendoloski) criteria", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21480669", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 426, "text": "molecular weight (MW) \u2264 500 or the logarithm of the octanol-water partition coefficient, log P(o/w) < 5, are anticipated to likely have pharmacokinetic properties appropriate for oral administration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21142079", "endSection": "abstract" }, { "offsetInBeginSection": 833, "offsetInEndSection": 916, "text": " MW, log P(o/w), number of hydrogen bond donors, and number of hydrogen acceptors, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21142079", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 502, "text": " Using a set of six physicochemical parameters ((a) lipophilicity, calculated partition coefficient (ClogP); (b) calculated distribution coefficient at pH = 7.4 (ClogD); (c) molecular weight (MW); (d) topological polar surface area (TPSA); (e) number of hydrogen bond donors (HBD); (f) most basic center (pK(a)))", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22778837", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 739, "text": ". Selected rules include size, lipophilicity, polarizability, charge, flexibility, rigidity, and hydrogen bond capacity. For these, extreme values were set, e.g., maximum molecular weight 1500, calculated negative logarithm of the octanol/water partition between -10 and 20, and up to 30 nonterminal rotatable bonds", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11300855", "endSection": "abstract" }, { "offsetInBeginSection": 1088, "offsetInEndSection": 1404, "text": "We first uncovered three important structure-related criteria closely related to drug-likeness, namely: (1) the best numbers of aromatic and non-aromatic rings are 2 and 1, respectively; (2) the best functional groups of candidate drugs are usually -OH, -COOR and -COOH in turn, but not -CONHOH, -SH, -CHO and -SO3H.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26771590", "endSection": "abstract" } ] }, { "body": "Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33210357", "http://www.ncbi.nlm.nih.gov/pubmed/32514935", "http://www.ncbi.nlm.nih.gov/pubmed/32474043", "http://www.ncbi.nlm.nih.gov/pubmed/33201001", "http://www.ncbi.nlm.nih.gov/pubmed/33842874", "http://www.ncbi.nlm.nih.gov/pubmed/34611496", "http://www.ncbi.nlm.nih.gov/pubmed/33614350", "http://www.ncbi.nlm.nih.gov/pubmed/33038021", "http://www.ncbi.nlm.nih.gov/pubmed/34599472", "http://www.ncbi.nlm.nih.gov/pubmed/32757246", "http://www.ncbi.nlm.nih.gov/pubmed/33085063", "http://www.ncbi.nlm.nih.gov/pubmed/32579597", "http://www.ncbi.nlm.nih.gov/pubmed/33231487", "http://www.ncbi.nlm.nih.gov/pubmed/32651067", "http://www.ncbi.nlm.nih.gov/pubmed/33891615", "http://www.ncbi.nlm.nih.gov/pubmed/32422062", "http://www.ncbi.nlm.nih.gov/pubmed/32587982", "http://www.ncbi.nlm.nih.gov/pubmed/32685191", "http://www.ncbi.nlm.nih.gov/pubmed/32875060", "http://www.ncbi.nlm.nih.gov/pubmed/33658619", "http://www.ncbi.nlm.nih.gov/pubmed/33222020", "http://www.ncbi.nlm.nih.gov/pubmed/33748156", "http://www.ncbi.nlm.nih.gov/pubmed/32485082", "http://www.ncbi.nlm.nih.gov/pubmed/33981731", "http://www.ncbi.nlm.nih.gov/pubmed/32611676", "http://www.ncbi.nlm.nih.gov/pubmed/32320478", "http://www.ncbi.nlm.nih.gov/pubmed/32558877", "http://www.ncbi.nlm.nih.gov/pubmed/32348166", "http://www.ncbi.nlm.nih.gov/pubmed/32737124", "http://www.ncbi.nlm.nih.gov/pubmed/33095513", "http://www.ncbi.nlm.nih.gov/pubmed/32242182", "http://www.ncbi.nlm.nih.gov/pubmed/33504565", "http://www.ncbi.nlm.nih.gov/pubmed/34155486", "http://www.ncbi.nlm.nih.gov/pubmed/32918209", "http://www.ncbi.nlm.nih.gov/pubmed/32965603" ], "ideal_answer": [ "No. Patients receiving angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) should continue treatment with these agents if there is no other reason for discontinuation. Despite speculation that patients with COVID-19 who are receiving these agents may be at increased risk for adverse outcomes, accumulating evidence does not support an association of ACE inhibitors and ARBs with more severe disease. In addition, stopping these agents in some patients can exacerbate comorbid cardiovascular or kidney disease and increase mortality.", "ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death.", "No. ACEIs and ARBs have not been shown to increase the likelihood of severe COVID-19 hospitalization." ], "exact_answer": "no", "type": "yesno", "id": "6276d2d956bf9aee6f000002", "snippets": [ { "offsetInBeginSection": 1495, "offsetInEndSection": 1726, "text": "These findings suggest that the use of ACE-I and ARB is not associated with adverse outcomes and may be associated with improved outcomes in COVID-19, which is immediately relevant to care of the many patients on these medications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34611496", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 181, "text": "There are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599472", "endSection": "abstract" }, { "offsetInBeginSection": 1085, "offsetInEndSection": 1311, "text": "ACEIs and ARBs were associated with a slight reduction in Covid-19 hospitalization risk compared with treatment with other first-line antihypertensives (OR for ACEIs 0.95, 95% CI 0.92-0.98; OR for ARBs 0.94, 95% CI 0.90-0.97).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599472", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1505, "text": "There were no meaningful differences in risk for ACEIs compared with ARBs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599472", "endSection": "abstract" }, { "offsetInBeginSection": 1795, "offsetInEndSection": 1972, "text": "ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599472", "endSection": "abstract" }, { "offsetInBeginSection": 1346, "offsetInEndSection": 1448, "text": "In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33222020", "endSection": "abstract" }, { "offsetInBeginSection": 1542, "offsetInEndSection": 1687, "text": "Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33222020", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1258, "text": "Random-effects meta-analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID-19 patients (odds ratio [OR]\u2009=\u20090.624, 95% confidence interval [CI]\u2009=\u20090.457-0.852, p\u2009=\u2009.003, I2 \u2009=\u200974.3%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33095513", "endSection": "abstract" }, { "offsetInBeginSection": 1562, "offsetInEndSection": 1864, "text": "In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR\u2009=\u20090.682, 95% CI\u2009=\u20090.475-1.978, p\u2009=\u2009.037, I2 \u2009=\u20090.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID-19 pandemic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33095513", "endSection": "abstract" }, { "offsetInBeginSection": 942, "offsetInEndSection": 1317, "text": "Use of ACE-I or ARB medications was not associated with increased risk of hospitalization, intensive care unit admission, or death. Compared to patients with charted past medical history, there was a lower risk of hospitalization for patients on ACE-I (odds ratio (OR) 0.43; 95% confidence interval (CI) 0.19-0.97; P = 0.0426) and ARB (OR 0.39; 95% CI 0.17-0.90; P = 0.0270).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34611496", "endSection": "abstract" }, { "offsetInBeginSection": 1092, "offsetInEndSection": 1642, "text": "The second analysis showed that the use of ACEI and/or ARB did not affect in-hospital mortality (risk ratio [RR] 95% [CI]]\u2009=\u20090.88 [0.64-1.20], p\u2009=\u20090.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (RR [CI]\u2009=\u20090.66 [0.49-0.89], p\u2009=\u20090.004). Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID-19 nor with mortality of COVID-19 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33038021", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1513, "text": "ACEIs/ARBs are protective factors against mortality in COVID-19 patients with HTN, and these agents can be considered potential therapeutic options in this disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33085063", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32242182", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1201, "text": "Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV\u20112 infections", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32514935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32242182", "endSection": "abstract" }, { "offsetInBeginSection": 1537, "offsetInEndSection": 1601, "text": "ACEIs and ARBs do not promote a more severe outcome of COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32965603", "endSection": "abstract" }, { "offsetInBeginSection": 626, "offsetInEndSection": 936, "text": "Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32757246", "endSection": "abstract" }, { "offsetInBeginSection": 937, "offsetInEndSection": 1218, "text": "Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32757246", "endSection": "abstract" }, { "offsetInBeginSection": 1476, "offsetInEndSection": 1658, "text": "On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32757246", "endSection": "abstract" }, { "offsetInBeginSection": 26, "offsetInEndSection": 271, "text": "Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32474043", "endSection": "abstract" }, { "offsetInBeginSection": 1180, "offsetInEndSection": 1472, "text": "Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32320478", "endSection": "abstract" } ] }, { "body": "Which small molecules inhibit the c-Myc/Max dimerization?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18288422", "http://www.ncbi.nlm.nih.gov/pubmed/23801058", "http://www.ncbi.nlm.nih.gov/pubmed/24859015", "http://www.ncbi.nlm.nih.gov/pubmed/19114306", "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "http://www.ncbi.nlm.nih.gov/pubmed/16873022", "http://www.ncbi.nlm.nih.gov/pubmed/19432426", "http://www.ncbi.nlm.nih.gov/pubmed/17046567", "http://www.ncbi.nlm.nih.gov/pubmed/31679823", "http://www.ncbi.nlm.nih.gov/pubmed/25114221", "http://www.ncbi.nlm.nih.gov/pubmed/30880155", "http://www.ncbi.nlm.nih.gov/pubmed/20801893", "http://www.ncbi.nlm.nih.gov/pubmed/25306215", "http://www.ncbi.nlm.nih.gov/pubmed/26474287" ], "ideal_answer": [ "Mycros are the first inhibitors of c-Myc/Max dimerization, which have been demonstrated to inhibit DNA binding of c-Myc with preference over other dimeric transcription factors in vitroMost Myc inhibitors prevent the association between Myc and its obligate heterodimerization partner Max via their respective bHLH-ZIP domainsPreviously we showed that two c-Myc-Max inhibitors, 10058-F4 and 10074-G5, bound to distinct ID regions of the monomeric c-Myc bHLHZip domainWe tested the efficacy of Mycro3, a small-molecule inhibitor of Myc-Max dimerizationIn a fluorescence polarization screen for the MYC-MAX interaction, we have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kr\u00f6hnke pyridine libraryWe have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor models with MYCN overexpressionWe developed a series of small-molecule MYC inhibitors that engage MYC inside cells, disrupt MYC/MAX dimers, and impair MYC-driven gene expression.Inhibition of MYC/MAX dimerization by a small-molecule antagonist (IIA6B17) has been shown to interfere with MYC-induced transformation of chick embryo fibroblasts, suggesting that the functional inhibitors of the MYC family of oncoproteins have potential as therapeutic agents.", "The small molecules that inhibit c-Myc/Max dimerization are Mycro1, Mycro2, Mycro3, IIA6B17, celastrol, 10058-F4, 10074-G5, JY-3-094, KJ-Pyr-9, MYCi361 and MYCi975" ], "exact_answer": [ [ "Mycro1", "Mycro1" ], [ "Mycro2", "Mycro2" ], [ "Mycro3", "Mycro3" ], [ "IIA6B17", "IIA6B17" ], [ "celastrol", "celastrol" ], [ "10058-F4", "10058-F4" ], [ "10074-G5", "10074-G5" ], [ "JY-3-094", "generated an analog, JY-3-094" ], [ "KJ-Pyr-9", "KJ-Pyr-9" ], [ "MYCi361", "MYCi361" ], [ "MYCi975", "MYCi975" ] ], "type": "list", "id": "6275199fe764a5320400004d", "snippets": [ { "offsetInBeginSection": 344, "offsetInEndSection": 686, "text": "We have identified two small molecules, dubbed Mycro1 and Mycro2, which inhibit the protein-protein interactions between the bHLHZip proteins c-Myc and Max. Mycros are the first inhibitors of c-Myc/Max dimerization, which have been demonstrated to inhibit DNA binding of c-Myc with preference over other dimeric transcription factors in vitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16873022", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 423, "text": "We tested the efficacy of Mycro3, a small-molecule inhibitor of Myc-Max dimerization", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25306215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 278, "text": "Inhibition of MYC/MAX dimerization by a small-molecule antagonist (IIA6B17) has been shown to interfere with MYC-induced transformation of chick embryo fibroblasts, suggesting that the functional inhibitors of the MYC family of oncoproteins have potential as therapeutic agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18288422", "endSection": "abstract" }, { "offsetInBeginSection": 212, "offsetInEndSection": 515, "text": "We report here that the naturally-occurring triterpenoid celastrol is an inhibitor of the c-Myc (Myc) oncoprotein, which is over-expressed in many human cancers. Most Myc inhibitors prevent the association between Myc and its obligate heterodimerization partner Max via their respective bHLH-ZIP domains", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26474287", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 555, "text": "One approach to its inhibition has been to disrupt the dimeric complex formed between its basic helix-loop-helix leucine zipper (bHLHZip) domain and a similar domain on its dimerization partner, Max. As monomers, bHLHZip proteins are intrinsically disordered (ID). Previously we showed that two c-Myc-Max inhibitors, 10058-F4 and 10074-G5, bound to distinct ID regions of the monomeric c-Myc bHLHZip domain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19432426", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 653, "text": "We have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor models with MYCN overexpression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859015", "endSection": "abstract" }, { "offsetInBeginSection": 335, "offsetInEndSection": 590, "text": "We have recently reported a structure-activity relationship study of one such small molecule, 10074-G5, and generated an analog, JY-3-094, with significantly improved ability to prevent or disrupt the association between recombinant Myc and Max proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23801058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "In a fluorescence polarization screen for the MYC-MAX interaction, we have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kr\u00f6hnke pyridine library", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25114221", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 748, "text": "We developed a series of small-molecule MYC inhibitors that engage MYC inside cells, disrupt MYC/MAX dimers, and impair MYC-driven gene expression. The compounds enhance MYC phosphorylation on threonine-58, consequently increasing proteasome-mediated MYC degradation. The initial lead, MYC inhibitor 361 (MYCi361), suppressed in\u00a0vivo tumor growth in mice, increased tumor immune cell infiltration, upregulated PD-L1 on tumors, and sensitized tumors to anti-PD1 immunotherapy. However, 361 demonstrated a narrow therapeutic index. An improved analog, MYCi975 showed better tolerability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31679823", "endSection": "abstract" }, { "offsetInBeginSection": 333, "offsetInEndSection": 482, "text": "is. Inhibition of the c-Myc/Max heterodimerization by the recently identified small-molecule compound, 10058-F4, might be a novel antileukemic strate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046567", "endSection": "abstract" }, { "offsetInBeginSection": 665, "offsetInEndSection": 820, "text": "ecule 10074-G5 is an inhibitor of c-Myc-Max dimerization (IC50 =146\u2005\u03bcM) that operates by binding and stabilizing c-Myc in its monomeric form. We have ident", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "endSection": "abstract" }, { "offsetInBeginSection": 346, "offsetInEndSection": 658, "text": "have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor models with MYCN overexpression. Our", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859015", "endSection": "abstract" }, { "offsetInBeginSection": 627, "offsetInEndSection": 786, "text": "ered the asymmetric polycyclic lactam, KI-MS2-008, which stabilizes the Max homodimer while reducing Myc protein and Myc-regulated transcript levels. KI-MS2-00", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30880155", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 526, "text": "mall molecule 7-nitro-N-(2-phenylphenyl)-2,1,3-benzoxadiazol-4-amine (10074-G5) binds to and distorts the bHLH-ZIP domain of c-Myc, thereby inhibiting c-Myc/Max heterodimer formation and inhibiting its transcriptional activity. We repor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20801893", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 505, "text": "ave identified two small molecules, dubbed Mycro1 and Mycro2, which inhibit the protein-protein interactions between the bHLHZip proteins c-Myc and Max. Mycr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16873022", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1628, "text": " indicated that 3jc48-3 inhibits c-Myc-Max dimerization in cells, which was further substantiated by the specific silencing of a c-Myc-driven luciferase reporter gene. Finally, 3jc48-3's intracellu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 654, "text": "We have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor models with MYCN overexpression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859015", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 806, "text": "The small molecule 10074-G5 is an inhibitor of c-Myc-Max dimerization (IC50 =146\u2005\u03bcM) that operates by binding and stabilizing c-Myc in its monomeric form.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1065, "text": "We have identified a congener of 10074-G5, termed 3jc48-3 (methyl 4'-methyl-5-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-[1,1'-biphenyl]-3-carboxylate), that is about five times as potent (IC50 =34\u2005\u03bcM) at inhibiting c-Myc-Max dimerization as the parent compound.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 805, "text": "The small molecule 10074-G5 is an inhibitor of c-Myc-Max dimerization (IC50 =146\u2005\u03bcM) that operates by binding and stabilizing c-Myc in its monomeric form", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "endSection": "abstract" }, { "offsetInBeginSection": 807, "offsetInEndSection": 1064, "text": "We have identified a congener of 10074-G5, termed 3jc48-3 (methyl 4'-methyl-5-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-[1,1'-biphenyl]-3-carboxylate), that is about five times as potent (IC50 =34\u2005\u03bcM) at inhibiting c-Myc-Max dimerization as the parent compound", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "endSection": "abstract" }, { "offsetInBeginSection": 1532, "offsetInEndSection": 1688, "text": "Importantly, 10074-G5 and 10058-F4 were the most efficient in inducing neuronal differentiation and lipid accumulation in MYCN-amplified neuroblastoma cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24859015", "endSection": "abstract" }, { "offsetInBeginSection": 326, "offsetInEndSection": 743, "text": "mogenesis. Inhibition of the c-Myc/Max heterodimerization by the recently identified small-molecule compound, 10058-F4, might be a novel antileukemic strategy.MATERIALS AND METHODS: HL-60, U937, and NB4 cells and primary AML cells were used to examine the effects of 10058-F4 on apoptosis and myeloid differentiation.RESULTS: We showed that 10058-F4 arrested AML cells at G0/G1 phase, downregulated c-Myc expression a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17046567", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Discovery of methyl 4'-methyl-5-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-[1,1'-biphenyl]-3-carboxylate, an improved small-molecule inhibitor of c-Myc-max dimerization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24976143", "endSection": "title" }, { "offsetInBeginSection": 285, "offsetInEndSection": 517, "text": "The small molecule 7-nitro-N-(2-phenylphenyl)-2,1,3-benzoxadiazol-4-amine (10074-G5) binds to and distorts the bHLH-ZIP domain of c-Myc, thereby inhibiting c-Myc/Max heterodimer formation and inhibiting its transcriptional activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20801893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20801893", "endSection": "title" }, { "offsetInBeginSection": 298, "offsetInEndSection": 524, "text": "We show that the effect of 10058-F4 (a small-molecule that binds disordered c-Myc monomers and disrupts the c-Myc-Max complex) on both c-Myc-Max heterodimerization and DNA binding is dependent on the nature of the Max isoform.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19114306", "endSection": "abstract" } ] }, { "body": "Which models are used for predicting disease progression in Duchenne Muscular Dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30571821", "http://www.ncbi.nlm.nih.gov/pubmed/28643370", "http://www.ncbi.nlm.nih.gov/pubmed/31960231", "http://www.ncbi.nlm.nih.gov/pubmed/22248373", "http://www.ncbi.nlm.nih.gov/pubmed/32184340", "http://www.ncbi.nlm.nih.gov/pubmed/6863354", "http://www.ncbi.nlm.nih.gov/pubmed/34877803" ], "ideal_answer": [ "Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach.", "Models used to predict disease progression of Duchenne Muscular Dyystrophy are: cumulative distribution function using a non-linear mixed effects approach, ...", "Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach. Longitudinal progression of Duchenne Muscular Dystrophy was also modeled using a weighted average probability method. Duchenne muscular dystrophy disease progression was modeled using the following models: linear progression function, logarithmological, multisubunit, linear multiple-parametry, and linear multiple sum", "Modeling disease trajectory in Duchenne muscular dystrophy Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach." ], "exact_answer": [ [ "cumulative distribution function using a non-linear mixed effects approach" ], [ "nonlinear mixed-effects" ], [ "latent process models" ], [ "bayesian models" ], [ "linear regression model" ], [ "multiple regression model" ], [ "multiple logistic regression model" ], [ "Kaplan-Meier survival analysis" ], [ "Cox-Snell's proportional risk model" ] ], "type": "list", "id": "6278df3c56bf9aee6f000015", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 58, "text": "Modeling disease trajectory in Duchenne muscular dystrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32184340", "endSection": "title" }, { "offsetInBeginSection": 589, "offsetInEndSection": 718, "text": "Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32184340", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Developing a Natural History Progression Model for Duchenne Muscular Dystrophy Using the Six-Minute Walk Test", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28643370", "endSection": "title" }, { "offsetInBeginSection": 370, "offsetInEndSection": 600, "text": "jective of this study was to enhance the quantitative understanding of DMD disease progression through nonlinear mixed effects modeling of the population mean and variability of the 6-min walk test (6MWT) clinical endpoint. An ind", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31960231", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Latent process model of the 6-minute walk test in Duchenne muscular dystrophy : A Bayesian approach to quantifying rare disease progression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31960231", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 492, "text": " objective was to inform the design of DMD clinical trials by developing a disease progression model-based clinical trial simulation (CTS) platform based on measures commonly used in DMD trials. Dat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34877803", "endSection": "abstract" }, { "offsetInBeginSection": 700, "offsetInEndSection": 857, "text": "Model simulations using age demographics from a previous DMD natural history study could reasonably predict the trend in improvement and decline in the 6MWT.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28643370", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 284, "text": " Data from the records of fifty patients were analyzed by linear and multiple regression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6863354", "endSection": "abstract" }, { "offsetInBeginSection": 605, "offsetInEndSection": 785, "text": "multiple logistic regression analysis on routine clinical data was performed to identify parameters that can find abnormal LV contraction, and to develop a weighted scoring system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22248373", "endSection": "abstract" }, { "offsetInBeginSection": 970, "offsetInEndSection": 1080, "text": "Kaplan Meier survival analysis was applied, where global survival was defined between birth and age of death. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30571821", "endSection": "abstract" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1176, "text": "he determinant factors analyzed were estimated through the Cox-Snell's proportional risk model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30571821", "endSection": "abstract" } ] }, { "body": "What links muscle cellular pathways to ALS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20007902", "http://www.ncbi.nlm.nih.gov/pubmed/29765840", "http://www.ncbi.nlm.nih.gov/pubmed/15657392", "http://www.ncbi.nlm.nih.gov/pubmed/19889637", "http://www.ncbi.nlm.nih.gov/pubmed/25602021", "http://www.ncbi.nlm.nih.gov/pubmed/26041991", "http://www.ncbi.nlm.nih.gov/pubmed/34137441", "http://www.ncbi.nlm.nih.gov/pubmed/32986860", "http://www.ncbi.nlm.nih.gov/pubmed/34776863", "http://www.ncbi.nlm.nih.gov/pubmed/22996383", "http://www.ncbi.nlm.nih.gov/pubmed/30682329", "http://www.ncbi.nlm.nih.gov/pubmed/26775178", "http://www.ncbi.nlm.nih.gov/pubmed/33661767", "http://www.ncbi.nlm.nih.gov/pubmed/34357138", "http://www.ncbi.nlm.nih.gov/pubmed/27195289", "http://www.ncbi.nlm.nih.gov/pubmed/34018075" ], "ideal_answer": [ "Changes to muscle cellular pathways may occur downstream of motor neuron pathology in ALS. Genetic changes to pathways that are important to muscle function may also be causal of the disease. In addition, changes to the muscle may be responsible for motor neuron death. Pathological changes occur in muscle before disease onset and independent from MN degeneration, and the muscle may release toxic elements, such as via extracellular vesicle secretion. Muscle metabolism and mitochondrial activity, RNA processing, tissue-resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood, are all deregulated in ALS. There may also be a link between motor neuron death, the immune system, and muscle cells, as muscle-resident glial cells have been shown to activate upon nerve injury. Muscle-restricted expression of a localized insulin-like growth factor Igf-1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1(G93A) transgenic mice." ], "type": "summary", "id": "6273a2fde764a53204000048", "snippets": [ { "offsetInBeginSection": 301, "offsetInEndSection": 553, "text": "Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34357138", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 686, "text": "Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34357138", "endSection": "abstract" }, { "offsetInBeginSection": 570, "offsetInEndSection": 904, "text": " In this sense, molecular mechanisms essential for cell and tissue homeostasis have been shown to be deregulated in the disease. These include muscle metabolism and mitochondrial activity, RNA processing, tissue-resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32986860", "endSection": "abstract" }, { "offsetInBeginSection": 125, "offsetInEndSection": 259, "text": "ALS pathology originates at a single site and spreads in an organized and prion-like manner, possibly driven by extracellular vesicles", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34776863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Here, we report on the identification of Itga7-expressing muscle-resident glial cells activated by loss of neuromuscular junction (NMJ) integrity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33661767", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 609, "text": "muscle-restricted expression of a localized insulin-like growth factor (Igf) -1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1(G93A) transgenic mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15657392", "endSection": "abstract" }, { "offsetInBeginSection": 1379, "offsetInEndSection": 1579, "text": "rovide the evidence that the cytoprotective autophagy pathway is suppressed in G93A skeletal muscle and this suppression may link to the enhanced apoptosis during ALS progression. The abnormal autopha", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25602021", "endSection": "abstract" }, { "offsetInBeginSection": 840, "offsetInEndSection": 1080, "text": "n overview of ALS pathophysiology, with a focus on the role of skeletal muscle, we review the current literature on myomiR network dysregulation as a contributing factor to myogenic perturbations and muscle atrophy in ALS. We argue that, in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34137441", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 579, "text": "e the death of motor neuron is a defining hallmark of ALS, accumulated evidences suggested that in addition to being a victim of motor neuron axonal withdrawal, the intrinsic skeletal muscle degeneration may also actively contribute to ALS disease pathogenesis and progression. Exam", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30682329", "endSection": "abstract" }, { "offsetInBeginSection": 412, "offsetInEndSection": 738, "text": "h recent studies support the potential therapeutic benefits of targeting the skeletal muscle in ALS, relatively little is known about inflammation and glial responses in skeletal muscle and near NMJs, or how these responses contribute to motor neuron survival, neuromuscular innervation, or motor dysfunction in ALS. We recent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26775178", "endSection": "abstract" }, { "offsetInBeginSection": 1358, "offsetInEndSection": 1558, "text": "Taking together, we provide the evidence that the cytoprotective autophagy pathway is suppressed in G93A skeletal muscle and this suppression may link to the enhanced apoptosis during ALS progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25602021", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 282, "text": "Although the primary symptom of ALS is muscle weakness, the link between SOD1 mutations, cellular dysfunction and muscle atrophy and weakness is not well understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26041991", "endSection": "abstract" }, { "offsetInBeginSection": 1783, "offsetInEndSection": 1936, "text": "These data suggest a mechanism by which myocellular ER stress leads to reduced protein translation and contributes to muscle atrophy and weakness in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26041991", "endSection": "abstract" }, { "offsetInBeginSection": 1559, "offsetInEndSection": 1680, "text": "The abnormal autophagy activity in skeletal muscle likely contributes muscle degeneration and disease progression in ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25602021", "endSection": "abstract" } ] }, { "body": "For what known mutations is KRAS gene considered to be oncogenic?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20385028", "http://www.ncbi.nlm.nih.gov/pubmed/25941399", "http://www.ncbi.nlm.nih.gov/pubmed/32956987", "http://www.ncbi.nlm.nih.gov/pubmed/25359494", "http://www.ncbi.nlm.nih.gov/pubmed/31289513", "http://www.ncbi.nlm.nih.gov/pubmed/25257576", "http://www.ncbi.nlm.nih.gov/pubmed/22247021", "http://www.ncbi.nlm.nih.gov/pubmed/26970110", "http://www.ncbi.nlm.nih.gov/pubmed/31309326", "http://www.ncbi.nlm.nih.gov/pubmed/20846262", "http://www.ncbi.nlm.nih.gov/pubmed/29453361", "http://www.ncbi.nlm.nih.gov/pubmed/20034871", "http://www.ncbi.nlm.nih.gov/pubmed/33618059", "http://www.ncbi.nlm.nih.gov/pubmed/22329297", "http://www.ncbi.nlm.nih.gov/pubmed/34822010", "http://www.ncbi.nlm.nih.gov/pubmed/33325140", "http://www.ncbi.nlm.nih.gov/pubmed/22232209", "http://www.ncbi.nlm.nih.gov/pubmed/30199525", "http://www.ncbi.nlm.nih.gov/pubmed/31827279", "http://www.ncbi.nlm.nih.gov/pubmed/31332011", "http://www.ncbi.nlm.nih.gov/pubmed/26701267", "http://www.ncbi.nlm.nih.gov/pubmed/25065594", "http://www.ncbi.nlm.nih.gov/pubmed/32176377", "http://www.ncbi.nlm.nih.gov/pubmed/34369256", "http://www.ncbi.nlm.nih.gov/pubmed/29650325", "http://www.ncbi.nlm.nih.gov/pubmed/9612526", "http://www.ncbi.nlm.nih.gov/pubmed/33860195", "http://www.ncbi.nlm.nih.gov/pubmed/11668624", "http://www.ncbi.nlm.nih.gov/pubmed/33709341", "http://www.ncbi.nlm.nih.gov/pubmed/23572025", "http://www.ncbi.nlm.nih.gov/pubmed/32308773", "http://www.ncbi.nlm.nih.gov/pubmed/19440799" ], "ideal_answer": [ "G12C, G12V, G12D and G12A are all observed mutations of the KRAS oncogene." ], "exact_answer": [ [ "G12C", "g12c", "KRAS G12C", "kras g12c" ], [ "G12V", "g12v", "KRAS G12V", "kras g12v" ], [ "G12D", "g12d", "KRAS G12D", "kras g12d" ], [ "G12A", "g12a", "KRAS G12A", "kras g12a" ] ], "type": "list", "id": "6278e49256bf9aee6f000017", "snippets": [ { "offsetInBeginSection": 113, "offsetInEndSection": 312, "text": "Mutations in KRAS - such as the G12C mutation - are found in most pancreatic, half of colorectal and a third of lung cancer cases and is thus responsible for a substantial proportion of cancer deaths", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32176377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "KRAS G12V mutation upregulates PD-L1 expression via TGF-\u03b2/EMT signaling pathway in human non-small-cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33325140", "endSection": "title" }, { "offsetInBeginSection": 1278, "offsetInEndSection": 1457, "text": "The most prevalent mutant subtype of KRAS in lung adenocarcinoma was G12C(9.88 %,56/567), followed by G12\u2009V(5.82 %,33/567), G12D(3.00 %,17/567), G12A(3.00 %,17/567), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32956987", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 394, "text": "Over 80% of oncogenic KRAS mutations occur at codon 12, where the glycine residue is substituted by different amino acids, leading to genomic heterogeneity of KRas-mutant tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33618059", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1155, "text": "KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26970110", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 381, "text": "Because oncogenic mutations occur in exons 2 or 3, two constitutively active KRAS proteins-each capable of transforming cells-are encoded when KRAS is activated by mutation2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31827279", "endSection": "abstract" }, { "offsetInBeginSection": 1033, "offsetInEndSection": 1303, "text": " KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13As", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385028", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 292, "text": "The majority of mutations are found at KRAS codons 12 and 13, and they appear to be more frequent in smokers and adenocarcinoma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20034871", "endSection": "abstract" }, { "offsetInBeginSection": 768, "offsetInEndSection": 957, "text": "To test this hypothesis, we analyzed 66 anal, vulvar, and head and neck SCC with known immunohistochemical p16(INK4a) and HPV DNA status for KRAS mutations in exon 2 (codons 12, 13, and 15)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25257576", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1118, "text": "6%) KRAS mutations in exon 1 (nine in codon 12 and one in codon 13), two missense mutations of BRAF (6%), one within exon 11 (G469A), and one V600E hot spot mutation in exon 15 of BRAF", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19440799", "endSection": "abstract" }, { "offsetInBeginSection": 1096, "offsetInEndSection": 1223, "text": "21); (3) KRAS(G12) and KRAS(G13) mutations are correlated, respectively, with the left and right colon cancer development (P<0.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23572025", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 276, "text": "The dominant oncogenic mutations of KRAS are single amino acid substitutions at codon 12, in particular G12D and G12V present in 60% to 70% of pancreatic cancers and 20% to 30% of colorectal cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26701267", "endSection": "abstract" }, { "offsetInBeginSection": 1013, "offsetInEndSection": 1598, "text": "CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.RESULTS: We found no evidence of KRAS oncogenic mutations in all analyzed tumors.CONCLUSIONS: This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20385028", "endSection": "abstract" }, { "offsetInBeginSection": 1449, "offsetInEndSection": 1559, "text": "Similarly, the most frequent KRAS oncogenic mutation G12D also drives K-RAS4B toward an exposed configuration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25941399", "endSection": "abstract" }, { "offsetInBeginSection": 64, "offsetInEndSection": 181, "text": "Traditionally, the oncogenic properties of KRAS missense mutants at position 12 (G12X) have been considered as equal.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30199525", "endSection": "abstract" }, { "offsetInBeginSection": 1377, "offsetInEndSection": 1559, "text": "The findings provide a basis to understand better the oncogenic properties of KRAS G12X mutants and the consequences of the observed nonrandom frequencies of specific G12X mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30199525", "endSection": "abstract" }, { "offsetInBeginSection": 951, "offsetInEndSection": 1450, "text": "In addition to testing for known actionable oncogenic driver alterations in EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, and NTRK and for the expression of programmed cell-death protein ligand 1, pathologists, medical oncologists, and community practitioners will need to incorporate routine testing for emerging biomarkers such as MET amplification, ERBB2 (alias HER2), and KRAS mutations, particularly KRAS G12C, considering the promising development of direct inhibitors of KRasG12C protein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33618059", "endSection": "abstract" }, { "offsetInBeginSection": 395, "offsetInEndSection": 607, "text": "The KRAS glycine-to-cysteine mutation (G12C) composes approximately 44% of KRAS mutations in non-small cell lung cancer, with mutant KRasG12C present in approximately 13% of all patients with lung adenocarcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33618059", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 881, "text": "1 is mechanistically distinct from covalent KRASG12C inhibitors because it binds to a different pocket present in both the active and inactive forms of KRAS", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31332011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Pancreatic cancer is almost invariably associated with mutations in the KRAS gene, most commonly KRASG12D, that result in a dominant-active form of the KRAS GTPase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22232209", "endSection": "abstract" }, { "offsetInBeginSection": 1057, "offsetInEndSection": 1320, "text": "Additionally, we show that KRASG13D/+ and KRASG13D/- cells have a distinct metabolic profile characterized by dysregulation of TCA cycle, up-regulation of glycolysis and glutathione metabolism pathway as well as increased glutamine uptake and acetate utilization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34822010", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Selective targeting of the oncogenic KRAS G12S mutant allele by CRISPR/Cas9 induces efficient tumor regression.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32308773", "endSection": "title" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1453, "text": "The most prevalent mutations among patients with PC are c.1621A>C (rs3822214) in KIT, c.38G>C (rs112445441) in KRAS and c.733G>A (rs28934575) in TP53 genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29650325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "KRAS codon 12 mutations in Australian non-small cell lung cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9612526", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "G12V and G12C mutations in the gene KRAS are associated with a poorer prognosis in primary colorectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31309326", "endSection": "title" }, { "offsetInBeginSection": 470, "offsetInEndSection": 566, "text": "In lung cancers, the mutations concentrate at codon 12 and mostly affect adenocarcinomas (ADCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20846262", "endSection": "abstract" }, { "offsetInBeginSection": 194, "offsetInEndSection": 245, "text": "KRASG12C represents only 11% of all KRAS mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33860195", "endSection": "abstract" }, { "offsetInBeginSection": 738, "offsetInEndSection": 1070, "text": "Most of the mutations were identified in codon 12 in 16 patients (61.5% of all mutations). We identified a novel mutation c.51\u00a0G>A in codon 17, where serine was substituted by arginine (S17R) in four patients. We also identified a very rare mutation, c.91\u00a0G>A, in which glutamic acid was replaced by lysine (E31K) in three patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34369256", "endSection": "abstract" }, { "offsetInBeginSection": 1042, "offsetInEndSection": 1295, "text": "Similar to the canonical mutants KRAS G12D and KRAS G13D, NIH3T3 cells overexpressing KRAS E31D and KRAS E63K showed altered morphology and were characteristically smaller, rounder, and highly refractile compared with their non-transformed counterparts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31289513", "endSection": "abstract" }, { "offsetInBeginSection": 645, "offsetInEndSection": 848, "text": "This system allowed us to rapidly compare the ability of 12 different KRAS mutations (G12A, G12C, G12D, G12F, G12R, G12S, G12V, G13C, G13D, Q61L, Q61R and A146T) to drive pancreatic tumorigenesis in vivo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25065594", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 125, "text": "dinucleotide KRAS2 mutations G12F and GG12-13VC.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11668624", "endSection": "title" }, { "offsetInBeginSection": 94, "offsetInEndSection": 178, "text": "New targeted therapies show preclinical promise in inhibiting the KRAS G12C variant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29453361", "endSection": "abstract" }, { "offsetInBeginSection": 1635, "offsetInEndSection": 1968, "text": "NSCLC cell lines with mutant KRas-Gly12Asp had activated phosphatidylinositol 3-kinase (PI-3-K) and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) signaling, whereas those with mutant KRas-Gly12Cys or mutant KRas-Gly12Val had activated Ral signaling and decreased growth factor-dependent Akt activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22247021", "endSection": "abstract" }, { "offsetInBeginSection": 827, "offsetInEndSection": 1066, "text": "Mutations were detected in 12 tumor samples: five patients with Gly12Val (GGT>GTT), three with Gly12Asp (GGT>GAT), two patients with Gly13Asp (GGC>GAC), one patient with Gly12Ser (GGT>AGT) and one with Gly12Cys (GGT>TGT) mutation in tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22329297", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1331, "text": "The G12D mutation was the most commonly encountered subtype in our cohort (21/50), whereas the G12C mutation was observed in 5 cases, and interestingly, this mutation was only seen in patients with non-small cell lung carcinoma (NSCLC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33709341", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25359494", "endSection": "title" } ] }, { "body": "Which proteins does the p85\u03b1 interact with?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29494137", "http://www.ncbi.nlm.nih.gov/pubmed/30651929", "http://www.ncbi.nlm.nih.gov/pubmed/21057544", "http://www.ncbi.nlm.nih.gov/pubmed/29740032", "http://www.ncbi.nlm.nih.gov/pubmed/16135792", "http://www.ncbi.nlm.nih.gov/pubmed/21266249", "http://www.ncbi.nlm.nih.gov/pubmed/28205613", "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "http://www.ncbi.nlm.nih.gov/pubmed/29300353", "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "http://www.ncbi.nlm.nih.gov/pubmed/24657164", "http://www.ncbi.nlm.nih.gov/pubmed/21827948", "http://www.ncbi.nlm.nih.gov/pubmed/20348926", "http://www.ncbi.nlm.nih.gov/pubmed/16219545" ], "ideal_answer": [ "p85\u03b1 interacts with itself, with p110\u03b1 and with p110d" ], "exact_answer": [ [ "p85\u03b1", "p85" ], [ "p110\u03b1", "p110" ], [ "p110\u03b4" ] ], "type": "list", "id": "6279392856bf9aee6f00001d", "snippets": [ { "offsetInBeginSection": 42, "offsetInEndSection": 69, "text": "p110\u03b4 interaction with p85\u03b1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21827948", "endSection": "title" }, { "offsetInBeginSection": 328, "offsetInEndSection": 370, "text": "regulatory interactions of p110\u03b4 with p85\u03b1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21827948", "endSection": "abstract" }, { "offsetInBeginSection": 241, "offsetInEndSection": 259, "text": "homodimerized p85\u03b1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "endSection": "abstract" }, { "offsetInBeginSection": 319, "offsetInEndSection": 348, "text": "p110\u03b1-free p85\u03b1 homodimerizes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "endSection": "abstract" }, { "offsetInBeginSection": 492, "offsetInEndSection": 526, "text": "homodimeric but not monomeric p85\u03b1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26222500", "endSection": "abstract" }, { "offsetInBeginSection": 63, "offsetInEndSection": 85, "text": "p110\u03b1-p85\u03b1 heterodimer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "endSection": "title" }, { "offsetInBeginSection": 691, "offsetInEndSection": 707, "text": "p110\u03b1-p85\u03b1 dimer", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "endSection": "abstract" }, { "offsetInBeginSection": 1206, "offsetInEndSection": 1226, "text": "p110\u03b1-p85\u03b1 interface", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26122737", "endSection": "abstract" }, { "offsetInBeginSection": 1194, "offsetInEndSection": 1353, "text": "kinase from hematopoietic cell lysates. The interaction between p85alpha-SH3 and BCR/ABL may be intermediated by proteins such as c-Cbl, Shc, Grb2, and/or Gab2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16219545", "endSection": "abstract" } ] }, { "body": "Computational tools for predicting allosteric pathways in proteins", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/20161451", "http://www.ncbi.nlm.nih.gov/pubmed/32737291", "http://www.ncbi.nlm.nih.gov/pubmed/25340971", "http://www.ncbi.nlm.nih.gov/pubmed/30688063", "http://www.ncbi.nlm.nih.gov/pubmed/27580047", "http://www.ncbi.nlm.nih.gov/pubmed/28282132", "http://www.ncbi.nlm.nih.gov/pubmed/23842804", "http://www.ncbi.nlm.nih.gov/pubmed/24803851", "http://www.ncbi.nlm.nih.gov/pubmed/23742907", "http://www.ncbi.nlm.nih.gov/pubmed/29750256", "http://www.ncbi.nlm.nih.gov/pubmed/27254668", "http://www.ncbi.nlm.nih.gov/pubmed/33844527" ], "ideal_answer": [ "CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities.", "We find that CARDS captures allosteric communication between the two cAMP-Binding Domains (CBDs)Overall, it is demonstrated that the communication pathways could be multiple and intrinsically disposed, and the MC path generation approach provides an effective tool for the prediction of key residues that mediate the allosteric communication in an ensemble of pathways and functionally plausible residuesWe utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM)Here, we introduce the Correlation of All Rotameric and Dynamical States (CARDS) framework for quantifying correlations between both the structure and disorder of different regions of a proteinWe present a novel method, \"MutInf\", to identify statistically significant correlated motions from equilibrium molecular dynamics simulationsCorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities.Here, a Monte Carlo (MC) path generation approach is proposed and implemented to define likely allosteric pathways through generating an ensemble of maximum probability paths.", "Here, a Monte Carlo (MC) path generation approach is proposed and implemented to define likely allosteric pathways through generating an ensemble of maximum probability paths. Overall, it is demonstrated that the communication pathways could be multiple and intrinsically disposed, and the MC path generation approach provides an effective tool for the prediction of key residues that mediate the allosteric communication in an ensemble of pathways and functionally plausible residues We utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM)", "A Monte Carlo (MC) path generation approach is proposed and implemented to define likely allosteric pathways through generating an ensemble of maximum probability paths. A novel method, \"MutInf\", to identify statistically significant correlated motions from equilibrium molecular dynamics simulations. CorrSite identifies potential alloster-binding sites based on motion correlation analyses between cavities. The Correlation of All Rotameric and Dynamical States (CARDS) framework for quantifying correlations between both the structure and disorder of different regions of a protein", "Computational tools for predicting allosteric pathways in proteins include MCPath, MutInf, pySCA, CorrSite, and CARDS." ], "exact_answer": [ [ "MCPath" ], [ "MutInf" ], [ "pySCA" ], [ "CorrSite" ], [ "CARDS" ] ], "type": "list", "id": "6278cb6056bf9aee6f00000d", "snippets": [ { "offsetInBeginSection": 181, "offsetInEndSection": 356, "text": "Here, a Monte Carlo (MC) path generation approach is proposed and implemented to define likely allosteric pathways through generating an ensemble of maximum probability paths.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742907", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1116, "text": "Overall, it is demonstrated that the communication pathways could be multiple and intrinsically disposed, and the MC path generation approach provides an effective tool for the prediction of key residues that mediate the allosteric communication in an ensemble of pathways and functionally plausible residues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742907", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 367, "text": "We present a novel method, \"MutInf\", to identify statistically significant correlated motions from equilibrium molecular dynamics simulations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20161451", "endSection": "abstract" }, { "offsetInBeginSection": 364, "offsetInEndSection": 742, "text": "The motion of residues and subunits underlies protein function; therefore, we hypothesized that the motions of allosteric and orthosteric sites are correlated. We utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27580047", "endSection": "abstract" }, { "offsetInBeginSection": 629, "offsetInEndSection": 799, "text": " To facilitate its usage, we present here the principles and practice of the SCA and introduce new methods for sector analysis in a python-based software package (pySCA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27254668", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 699, "text": "CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29750256", "endSection": "abstract" }, { "offsetInBeginSection": 441, "offsetInEndSection": 634, "text": "Here, we introduce the Correlation of All Rotameric and Dynamical States (CARDS) framework for quantifying correlations between both the structure and disorder of different regions of a protein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28282132", "endSection": "abstract" }, { "offsetInBeginSection": 1054, "offsetInEndSection": 1150, "text": "We find that CARDS captures allosteric communication between the two cAMP-Binding Domains (CBDs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28282132", "endSection": "abstract" }, { "offsetInBeginSection": 337, "offsetInEndSection": 486, "text": "overy. Allosite is a newly developed automatic tool for the prediction of allosteric sites in proteins of interest and is now available through a web", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23842804", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 668, "text": "e previously developed structure-based statistical mechanical model of allostery (SBSMMA), we share our experience in analyzing the allosteric signaling, predicting latent allosteric sites, inducing and tuning targeted allosteric response, and exploring the allosteric effects of mutations. This, yet i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33844527", "endSection": "abstract" }, { "offsetInBeginSection": 808, "offsetInEndSection": 1117, "text": "Overall, it is demonstrated that the communication pathways could be multiple and intrinsically disposed, and the MC path generation approach provides an effective tool for the prediction of key residues that mediate the allosteric communication in an ensemble of pathways and functionally plausible residues.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "MCPath: Monte Carlo path generation approach to predict likely allosteric pathways and functional residues.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23742907", "endSection": "title" }, { "offsetInBeginSection": 2022, "offsetInEndSection": 2046, "text": "Allosite and AllositePro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30688063", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 496, "text": "We develop a computationally efficient network-based method, Ohm, to identify and characterize allosteric communication networks within proteins", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32737291", "endSection": "abstract" }, { "offsetInBeginSection": 392, "offsetInEndSection": 702, "text": "To elaborate a rational description of allosteric coupling, we propose an original approach - MOdular NETwork Analysis (MONETA) - based on the analysis of inter-residue dynamical correlations to localize the propagation of both structural and dynamical effects of a perturbation throughout a protein structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340971", "endSection": "abstract" } ] }, { "body": "What are the classic signs of a basilar skull fracture?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19392601", "http://www.ncbi.nlm.nih.gov/pubmed/24095269", "http://www.ncbi.nlm.nih.gov/pubmed/2759776", "http://www.ncbi.nlm.nih.gov/pubmed/22951125", "http://www.ncbi.nlm.nih.gov/pubmed/30216260", "http://www.ncbi.nlm.nih.gov/pubmed/34236447", "http://www.ncbi.nlm.nih.gov/pubmed/717321", "http://www.ncbi.nlm.nih.gov/pubmed/1788430", "http://www.ncbi.nlm.nih.gov/pubmed/9800356" ], "ideal_answer": [ "Basilar skull fractures are fractures of the lower part of the skull. The four classic signs are:\n1. Periorbital ecchymosis (\u201craccoon eyes\u201d).\n2. Postauricular ecchymosis (Battle sign).\n3. CSF otorrhea or rhinorrhea (leakage of CSF, which is clear in appearance, from the ears or nose).\n4. Hemotympanum (blood behind the eardrum).", "Possible clinical signs are the presence of cerebrospinal fluid rhinorrhea or otorrhea, periorbital ecchymosis (raccoon eyes), retroauricular ecchymosis (battle sign) and cranial nerve injuries" ], "exact_answer": [ [ "Periorbital ecchymosis", "Raccoon eyes" ], [ "Postauricular ecchymosis", "Retroauricular ecchymosis", "Battle sign" ], [ "CSF rhinorrhea or otorrhea", "Cerebrospinal fluid rhinorrhea or otorrhea", "Rhinorrhea or otorrhea" ], [ "Hemotympanum" ] ], "type": "list", "id": "62793bad56bf9aee6f00001f", "snippets": [ { "offsetInBeginSection": 329, "offsetInEndSection": 522, "text": "Possible clinical signs are the presence of cerebrospinal fluid rhinorrhea or otorrhea, periorbital ecchymosis (raccoon eyes), retroauricular ecchymosis (battle sign) and cranial nerve injuries", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34236447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Although clinical signs for the diagnosis of basilar skull fracture (BSF) are ambiguous, they are widely used to make decisions on initial interventions involving trauma patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30216260", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 695, "text": "The following signs of BSF were considered: raccoon eyes, Battle's sign, otorrhea, and rhinorrhea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30216260", "endSection": "abstract" }, { "offsetInBeginSection": 332, "offsetInEndSection": 638, "text": "Included in the study were patients with hemotympanum alone or with hemotympanum plus additional clinical or roentgenographic signs of basilar skull fracture; patients with tympanic membrane perforation without otorrhea but with blood in the auditory canal; and children with either otorrhea or rhinorrhea.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/717321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "William Henry Battle (1855-1936) practiced medicine in England > 1 century ago and is primarily remembered for his description of ecchymosis over the mastoid, which indicates fracture of the skull base.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19392601", "endSection": "abstract" }, { "offsetInBeginSection": 785, "offsetInEndSection": 895, "text": "mainly expressing basilar fractures (as rhinorrhea, otorrhea, focal neurologic signs, retroauricular hematoma)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1788430", "endSection": "abstract" } ] }, { "body": "Which biomarkers are currently used for Duchenne Muscular Dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26091074", "http://www.ncbi.nlm.nih.gov/pubmed/30499689", "http://www.ncbi.nlm.nih.gov/pubmed/28252048", "http://www.ncbi.nlm.nih.gov/pubmed/26594036", "http://www.ncbi.nlm.nih.gov/pubmed/24813925", "http://www.ncbi.nlm.nih.gov/pubmed/28821969", "http://www.ncbi.nlm.nih.gov/pubmed/26963343", "http://www.ncbi.nlm.nih.gov/pubmed/31892637", "http://www.ncbi.nlm.nih.gov/pubmed/34439489", "http://www.ncbi.nlm.nih.gov/pubmed/32791870", "http://www.ncbi.nlm.nih.gov/pubmed/34533053", "http://www.ncbi.nlm.nih.gov/pubmed/23945935", "http://www.ncbi.nlm.nih.gov/pubmed/27778157", "http://www.ncbi.nlm.nih.gov/pubmed/27979502", "http://www.ncbi.nlm.nih.gov/pubmed/32390640", "http://www.ncbi.nlm.nih.gov/pubmed/21479190", "http://www.ncbi.nlm.nih.gov/pubmed/25150707", "http://www.ncbi.nlm.nih.gov/pubmed/27854211", "http://www.ncbi.nlm.nih.gov/pubmed/32695843", "http://www.ncbi.nlm.nih.gov/pubmed/31881125", "http://www.ncbi.nlm.nih.gov/pubmed/29554116", "http://www.ncbi.nlm.nih.gov/pubmed/31838454", "http://www.ncbi.nlm.nih.gov/pubmed/32476037", "http://www.ncbi.nlm.nih.gov/pubmed/24460924" ], "ideal_answer": [ "MRI measurements can be used as biomarkers of disease severity in ambulant patients with DMD. malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy", "MRI, fat fraction MRI, MRI mean T2, malate dehydrogenase 2 are some biomarkers that are used for DMD.", "malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophyMRI measurements can be used as biomarkers of disease severity in ambulant patients with DMD.", "MRI measurements can be used as biomarkers of disease severity in ambulant patients with DMD." ], "exact_answer": [ [ "MRI", "fat fraction MRI", "MRI mean T2", "qMR biomarkers" ], [ "malate dehydrogenase 2" ], [ "albumin thiol oxidation" ], [ "myostatin" ], [ "Interleukin 1 Receptor-Like 1 Protein", "ST2" ], [ "Extracellular dystrophy-associated miRNAs", "dystromiRs" ], [ "Troponin I" ], [ "Creatine kinase", "CK" ], [ "miR-499" ], [ "miR-191-5p" ], [ "miR-223" ], [ "miR-208a" ], [ "miR-206" ], [ "miR-103a-5p" ], [ "miR-103a-3p" ], [ "Serum Ostepontin", "OPN", "Ostepontin", "Serum OPN" ], [ "Pgam1" ], [ "Tnni3" ], [ "Camk2b" ], [ "Cycs" ], [ "Adamts5" ], [ "miR-30c" ], [ "miR-181a" ], [ "CNTN1" ], [ "SMAD3" ], [ "SIRT2" ], [ "HSP60" ], [ "MYBPC1" ], [ "GITR" ], [ "Titin" ], [ "miR-18a/b" ], [ "miR-498" ], [ "miR-144" ], [ "miR-182" ], [ "miR-23a/b" ], [ "miR-19a/b" ], [ "miR-200b/200c/429" ], [ "miR-124a" ], [ "MMP-9" ], [ "GDF-8" ], [ "FSTN" ], [ "a component of the DAG complex", "aDG-N" ] ], "type": "list", "id": "6278dc0c56bf9aee6f000010", "snippets": [ { "offsetInBeginSection": 1334, "offsetInEndSection": 1427, "text": "MRI measurements can be used as biomarkers of disease severity in ambulant patients with DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31892637", "endSection": "abstract" }, { "offsetInBeginSection": 50, "offsetInEndSection": 138, "text": "malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31881125", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Aim: Evaluate the utility of glutamate dehydrogenase (GLDH) and cardiac troponin I\u00a0as safety biomarkers, and creatine kinase\u00a0and muscle injury panel\u00a0as muscle health biomarkers in Duchenne muscular dystrop", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34533053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Myostatin Is a Quantifiable Biomarker for Monitoring Pharmaco-gene Therapy in Duchenne Muscular Dystrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32695843", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Extracellular microRNAs (miRNAs) are promising biomarkers of the inherited muscle wasting condition Duchenne muscular dystrophy, as they allow non-invasive monitoring of either disease progression or response to therapy. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945935", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Troponin I Levels Correlate with Cardiac MR LGE and Native T1 Values in Duchenne Muscular Dystrophy Cardiomyopathy and Identify Early Disease Progression", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32476037", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "OBJECTIVE: The diagnosis of Duchenne Muscular Dystrophy (DMD) currently depends on non-specific measures such as Creatine kinase (CK)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31838454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 93, "text": "Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26963343", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "Aim: Evaluate the utility of glutamate dehydrogenase (GLDH) and cardiac troponin I\u00a0as safety biomarkers, and creatine kinase\u00a0and muscle injury panel\u00a0as muscle health biomarkers in Duchenne muscular dystrophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34533053", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1010, "text": "Results for five leading candidate protein biomarkers (Pgam1, Tnni3, Camk2b, Cycs and Adamts5) were validated by ELISA in the mouse samples", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26594036", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 506, "text": "s observed. Therefore, three microRNAs (miRNAs), miR-1, miR-133a, and miR-206, were previously reported as alternative biomarkers for duchenne muscular dyst", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25150707", "endSection": "abstract" }, { "offsetInBeginSection": 595, "offsetInEndSection": 725, "text": "Conclusion: Results support the use of GLDH as a specific biomarker for liver injury in patients with Duchenne muscular dystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34533053", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 358, "text": "Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21479190", "endSection": "abstract" }, { "offsetInBeginSection": 674, "offsetInEndSection": 822, "text": ", albumin Cys34 undergoes thiol oxidation and these changes correlate with levels of protein thiol oxidation and damage of the dystrophic muscles. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34439489", "endSection": "abstract" }, { "offsetInBeginSection": 1016, "offsetInEndSection": 1165, "text": "We show that plasma albumin oxidation reflects muscle dystropathology, as increased after exercise and decreased after taurine treatment of mdx mice.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34439489", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1327, "text": "These data support the use of albumin thiol oxidation as a blood biomarker of dystropathology to assist with advancing clinical development of therapies for DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34439489", "endSection": "abstract" }, { "offsetInBeginSection": 798, "offsetInEndSection": 1080, "text": "Among a selected set of potential biomarkers for cardiomyopathy (MMP9, BNP, GAL3, CRP, LEP, TNC, TLR4 and ST2) we validated ST2 as significantly elevated in the serum of DMD cardiomyopathy group (35,798\u00a0\u00b1\u00a04884\u00a0pg/mL) compared to normal controls (9940\u00a0\u00b1\u00a02680\u00a0pg/mL; p\u00a0<\u00a00.01; n\u00a0=\u00a06).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28821969", "endSection": "abstract" }, { "offsetInBeginSection": 1081, "offsetInEndSection": 1207, "text": "Matrix metallopeptidase 9 (MMP9) levels were found significantly increased in both DMD groups compared to controls (p\u00a0<\u00a00.01).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28821969", "endSection": "abstract" }, { "offsetInBeginSection": 1289, "offsetInEndSection": 1434, "text": "Increased ST2 levels were found in serum of DMD subjects compared to healthy volunteers and further elevated in DMD subjects with cardiomyopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28821969", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Interleukin 1 Receptor-Like 1 Protein (ST2) is a Potential Biomarker for Cardiomyopathy in Duchenne Muscular Dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28821969", "endSection": "title" }, { "offsetInBeginSection": 418, "offsetInEndSection": 571, "text": " Extracellular dystrophy-associated miRNAs (dystromiRs) show dynamic patterns of expression that mirror the progression of muscle pathology in mdx mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945935", "endSection": "abstract" }, { "offsetInBeginSection": 572, "offsetInEndSection": 854, "text": "xpression of the myogenic miRNA, miR-206 and the myogenic transcription factor myogenin in the tibialis anterior muscle were found to positively correlate with serum dystromiR levels, suggesting that extracellular miRNAs are indicators of the regenerative status of the musculature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23945935", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1094, "text": "Our data revealed that miR-499 was significantly upregulated in all DMD patients, and true carriers (mothers), while 78 % of potential carriers (sisters) exhibited high levels of this miRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31838454", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1427, "text": "Similarly, miR-103a-3p showed an increase in the patients' families although to a lesser extent. On the other hand, miR-206 and miR-191-5p were significantly downregulated in the majority of the DMD patients and the tested female family members. MicroRNA miR-103a-5p and miR-208a followed a comparable trend in patients and mothers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31838454", "endSection": "abstract" }, { "offsetInBeginSection": 1365, "offsetInEndSection": 1500, "text": "OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26963343", "endSection": "abstract" }, { "offsetInBeginSection": 806, "offsetInEndSection": 1349, "text": "The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26963343", "endSection": "abstract" }, { "offsetInBeginSection": 948, "offsetInEndSection": 1321, "text": "There were very good inverse correlations between the levels of these miRNAs, especially miR-206, and functional performances: high levels corresponded to low muscle strength, muscle function, and quality of life. Moreover, by receiver operating characteristic curves analyses, we revealed that these miRNAs, especially miR-206, were able to discriminate DMD from controls.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24460924", "endSection": "abstract" }, { "offsetInBeginSection": 1328, "offsetInEndSection": 1502, "text": "miR-206 and other muscle-specific miRNAs in serum are useful for monitoring the DMD pathological progression, and hence as potential non-invasive biomarkers for the disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24460924", "endSection": "abstract" }, { "offsetInBeginSection": 1973, "offsetInEndSection": 2060, "text": "miR-206 and other muscle-specific miRNAs are useful as non-invasive biomarkers for DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24460924", "endSection": "abstract" }, { "offsetInBeginSection": 1012, "offsetInEndSection": 1100, "text": "Furthermore, ADAMTS5 was found to be significantly elevated in human DMD patient serum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26594036", "endSection": "abstract" }, { "offsetInBeginSection": 494, "offsetInEndSection": 710, "text": "Emerging MRI biomarkers of myocardial function and structure include the estimation of rotational mechanics and regional strain using MRI tagging; T1-mapping; and T2-mapping, a marker of inflammation, edema and fat. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30499689", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1245, "text": "Significant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|\u03c1| = 0.68-0.78), although measures in other rapidly progressing muscles including the biceps femoris (|\u03c1| = 0.63-0.73) and peroneals (|\u03c1| = 0.59-0.72) also showed strong correlations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554116", "endSection": "abstract" }, { "offsetInBeginSection": 1246, "offsetInEndSection": 1382, "text": "Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29554116", "endSection": "abstract" }, { "offsetInBeginSection": 865, "offsetInEndSection": 1102, "text": "Our results show that the serum levels of miR-30c and miR-181a increased 7- and 6-fold respectively in DMD patients (n\u2009=\u200921, 2-14 years, ambulant), and 7-fold in BMD patients (n\u2009=\u20095, 9-15 years) compared to controls (n\u2009=\u200922, 2-14 years).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27979502", "endSection": "abstract" }, { "offsetInBeginSection": 1196, "offsetInEndSection": 1360, "text": "However, there was a trend towards higher levels of miR-30c in DMD patients with better preserved motor function according to various motor scales and timed tests. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27979502", "endSection": "abstract" }, { "offsetInBeginSection": 1493, "offsetInEndSection": 1658, "text": "We propose miR-30c and miR-181a as reliable serum diagnostic biomarkers for DMD and BMD and miR-30c as a potential novel biomarker to assess disease severity in DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27979502", "endSection": "abstract" }, { "offsetInBeginSection": 1152, "offsetInEndSection": 1227, "text": "highlights novel mdx biomarkers (GITR, MYBPC1, HSP60, SIRT2, SMAD3, CNTN1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28252048", "endSection": "abstract" }, { "offsetInBeginSection": 1146, "offsetInEndSection": 1407, "text": "Furthermore, the five TFs ZNF362, ATAT1, SPI1, TCF12 and ABCF2, as well as the eight miRNAs miR-124a, miR-200b/200c/429, miR-19a/b, miR-23a/b, miR-182, miR-144, miR-498 and miR-18a/b were identified as playing crucial roles in the molecular pathogenesis of DMD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32791870", "endSection": "abstract" }, { "offsetInBeginSection": 602, "offsetInEndSection": 953, "text": "erein we examined the potential applicability of serum levels of matrix metalloproteinase 9 and matrix metalloproteinase 2, tissue inhibitor of metalloproteinases 1, myostatin (GDF-8) and follistatin (FSTN) as non-invasive biomarkers to distinguish between DMD steroid na\u00efve patients and healthy controls of similar age and also for carrier detection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26091074", "endSection": "abstract" }, { "offsetInBeginSection": 954, "offsetInEndSection": 1246, "text": "Our data suggest that serum levels of MMP-9, GDF-8 and FSTN are useful to discriminate DMD from controls (p < 0.05), to correlate with some neuromuscular assessments for DMD, and also to differentiate between Becker muscular dystrophy (BMD) and Limb-girdle muscular dystrophy (LGMD) patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26091074", "endSection": "abstract" }, { "offsetInBeginSection": 1008, "offsetInEndSection": 1509, "text": "carbonic anhydrase 3, microtubule associated protein 4 and collagen type I alpha 1 chain decline rather constantly over time, myosin light chain 3, electron transfer flavoprotein A, troponin T, malate dehydrogenase 2, lactate dehydrogenase B and nestin plateaus in early teens. Electron transfer flavoprotein A, correlates with the outcome of 6-minutes-walking-test whereas malate dehydrogenase 2 together with myosin light chain 3, carbonic anhydrase 3 and nestin correlate with respiratory capacity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32390640", "endSection": "abstract" }, { "offsetInBeginSection": 1464, "offsetInEndSection": 1660, "text": " a component of the DAG complex as a potential serum biomarker in DMD. Such a serum measure could be further developed as a tool to help reflect overall muscle DAG complex expression or stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27854211", "endSection": "abstract" } ] }, { "body": "What links lipid metabolism pathways to ALS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33113361", "http://www.ncbi.nlm.nih.gov/pubmed/34518331", "http://www.ncbi.nlm.nih.gov/pubmed/24600344", "http://www.ncbi.nlm.nih.gov/pubmed/31406145", "http://www.ncbi.nlm.nih.gov/pubmed/20362558", "http://www.ncbi.nlm.nih.gov/pubmed/33905537", "http://www.ncbi.nlm.nih.gov/pubmed/34343139", "http://www.ncbi.nlm.nih.gov/pubmed/33332650", "http://www.ncbi.nlm.nih.gov/pubmed/34623437", "http://www.ncbi.nlm.nih.gov/pubmed/34469619", "http://www.ncbi.nlm.nih.gov/pubmed/29904341", "http://www.ncbi.nlm.nih.gov/pubmed/32962914", "http://www.ncbi.nlm.nih.gov/pubmed/29410613", "http://www.ncbi.nlm.nih.gov/pubmed/28870551", "http://www.ncbi.nlm.nih.gov/pubmed/33707063", "http://www.ncbi.nlm.nih.gov/pubmed/34502460", "http://www.ncbi.nlm.nih.gov/pubmed/32656815", "http://www.ncbi.nlm.nih.gov/pubmed/32927603", "http://www.ncbi.nlm.nih.gov/pubmed/30767689", "http://www.ncbi.nlm.nih.gov/pubmed/33544228", "http://www.ncbi.nlm.nih.gov/pubmed/31562633", "http://www.ncbi.nlm.nih.gov/pubmed/34782793", "http://www.ncbi.nlm.nih.gov/pubmed/31848577", "http://www.ncbi.nlm.nih.gov/pubmed/26483191" ], "ideal_answer": [ "Dysregulation of lipid metabolism is observed early in the spinal cord of the SOD1 ALS mouse model, and abnormal levels of cholesterol and other lipids are observed in the blood and CNS of ALS patients. In addition, higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing ALS." ], "type": "summary", "id": "6273a317e764a53204000049", "snippets": [ { "offsetInBeginSection": 898, "offsetInEndSection": 1018, "text": "The meta-analyses identified few lipid metabolic pathways dysregulated early that were exacerbated at symptomatic stages", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34502460", "endSection": "abstract" }, { "offsetInBeginSection": 331, "offsetInEndSection": 464, "text": "abnormal level of cholesterol and other lipids in the circulation and central nervous system (CNS), has been reported in ALS patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34469619", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34518331", "endSection": "title" }, { "offsetInBeginSection": 1004, "offsetInEndSection": 1272, "text": "ion of these enzymes is upstream in the pathogenesis of neurodegenerative diseases and to support this we provide new evidence that ALS risk genes are enriched with genes involved in ceramide metabolism (P=0.019, OR = 2.54, Fisher exact test). Ceramide is a product of", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34623437", "endSection": "abstract" }, { "offsetInBeginSection": 707, "offsetInEndSection": 900, "text": "ions to lipid metabolism in neurons regulate processes linked to neurodegenerative diseases, and a link between dysfunction of lipid metabolism and ALS has also been proposed. In this review we", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33707063", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1836, "text": "ective. Taken together, our findings highlight the potential contribution of the carnitine shuttle and lipid beta oxidation in ALS and suggest strategies for therapeutic intervention based on restoring lipid metabolism in motor ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29904341", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 237, "text": "ing evidence suggests a link between changes in lipid metabolism and ALS. He", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26483191", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 771, "text": "eview, we will address the available data analyzing regarding the relationship of lipid metabolism and lipid derived- products with ALS. We will a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31562633", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "INTRODUCTION: Converging evidence highlights that lipid metabolism plays a key role in ALS p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28870551", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 805, "text": "dings indicate that cell adhesion, immune-inflammation response and lipid metabolism all play important roles in the onset of ALS. Detail", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20362558", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Medium-Chain Fatty Acids, Beta-Hydroxybutyric Acid and Genetic Modulation of the Carnitine Shuttle Are Protective in a Drosophila Model of ALS Base", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29904341", "endSection": "title" }, { "offsetInBeginSection": 528, "offsetInEndSection": 673, "text": "phic lateral sclerosis (ALS), dysfunctions in lipid metabolism and function have been identified as potential drivers of pathogenesis. In particu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29410613", "endSection": "abstract" }, { "offsetInBeginSection": 120, "offsetInEndSection": 254, "text": " study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations. Nu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33905537", "endSection": "abstract" }, { "offsetInBeginSection": 1020, "offsetInEndSection": 1149, "text": "Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33113361", "endSection": "abstract" }, { "offsetInBeginSection": 1288, "offsetInEndSection": 1472, "text": "Finally, hypermetabolism usually found in ALS patients should be considered too since all these metabolic changes could be compensation (or the cause) of the higher energy expenditure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33544228", "endSection": "abstract" }, { "offsetInBeginSection": 56, "offsetInEndSection": 148, "text": "Metabolic diseases and especially diabetes mellitus (DM) have been variously related to ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33544228", "endSection": "abstract" }, { "offsetInBeginSection": 145, "offsetInEndSection": 298, "text": "While a link between dysregulated lipid metabolism and ALS has been proposed, lipidome alterations involved in disease progression are still understudied", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31406145", "endSection": "abstract" }, { "offsetInBeginSection": 518, "offsetInEndSection": 661, "text": "In amyotrophic lateral sclerosis (ALS), dysfunctions in lipid metabolism and function have been identified as potential drivers of pathogenesis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29410613", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1350, "text": "ys. We present an insight into the pathological mechanisms in ALS, confirming that lipid metabolic alterations are transcriptionally dysregulated and are central to ALS aetiology, opening new options for the treatment of these devastating condit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34502460", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 250, "text": "This study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33905537", "endSection": "abstract" }, { "offsetInBeginSection": 661, "offsetInEndSection": 798, "text": "Our findings indicate that cell adhesion, immune-inflammation response and lipid metabolism all play important roles in the onset of ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20362558", "endSection": "abstract" }, { "offsetInBeginSection": 1616, "offsetInEndSection": 1844, "text": "Taken together, our findings highlight the potential contribution of the carnitine shuttle and lipid beta oxidation in ALS and suggest strategies for therapeutic intervention based on restoring lipid metabolism in motor neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29904341", "endSection": "abstract" }, { "offsetInBeginSection": 663, "offsetInEndSection": 912, "text": "In particular, aberrant lipid metabolism is proposed to underlie denervation of neuromuscular junctions, mitochondrial dysfunction, excitotoxicity, impaired neuronal transport, cytoskeletal defects, inflammation and reduced neurotransmitter release.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29410613", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 234, "text": "Growing evidence suggests a link between changes in lipid metabolism and ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26483191", "endSection": "abstract" }, { "offsetInBeginSection": 575, "offsetInEndSection": 663, "text": "Interestingly, lipidome alterations in motor cortex were mostly related to age than ALS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31406145", "endSection": "abstract" }, { "offsetInBeginSection": 1030, "offsetInEndSection": 1275, "text": "Although the mechanism leading to cholesteryl esters accumulation remains to be established, we postulate a hypothetical model based on neuroprotection of polyunsaturated fatty acids into lipid droplets in response to increased oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31406145", "endSection": "abstract" } ] }, { "body": "What is the multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34107136", "http://www.ncbi.nlm.nih.gov/pubmed/34246424", "http://www.ncbi.nlm.nih.gov/pubmed/33463127", "http://www.ncbi.nlm.nih.gov/pubmed/34881206", "http://www.ncbi.nlm.nih.gov/pubmed/33841438", "http://www.ncbi.nlm.nih.gov/pubmed/34203277", "http://www.ncbi.nlm.nih.gov/pubmed/32631771", "http://www.ncbi.nlm.nih.gov/pubmed/32755212", "http://www.ncbi.nlm.nih.gov/pubmed/33679227", "http://www.ncbi.nlm.nih.gov/pubmed/34880708", "http://www.ncbi.nlm.nih.gov/pubmed/32946801", "http://www.ncbi.nlm.nih.gov/pubmed/34087834", "http://www.ncbi.nlm.nih.gov/pubmed/33190340", "http://www.ncbi.nlm.nih.gov/pubmed/33872261", "http://www.ncbi.nlm.nih.gov/pubmed/33011038", "http://www.ncbi.nlm.nih.gov/pubmed/34507521", "http://www.ncbi.nlm.nih.gov/pubmed/34116467", "http://www.ncbi.nlm.nih.gov/pubmed/32923992", "http://www.ncbi.nlm.nih.gov/pubmed/34472807", "http://www.ncbi.nlm.nih.gov/pubmed/32966765", "http://www.ncbi.nlm.nih.gov/pubmed/34553691", "http://www.ncbi.nlm.nih.gov/pubmed/33743370", "http://www.ncbi.nlm.nih.gov/pubmed/33445833", "http://www.ncbi.nlm.nih.gov/pubmed/34509326" ], "ideal_answer": [ "Multisystem inflammatory syndrome in children (MIS-C) is a well described and documented condition that is associated with the active or recent COVID-19 infection. A similar presentation in adults is termed as Multisystem inflammatory syndrome in Adults (MIS-A). Multisystem inflammatory syndrome in children (MIS-C) is a novel, life-threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This disease has created a diagnostic challenge due to overlap with Kawasaki disease (KD) and KD shock syndrome. The majority of patients with MIS-C present with the involvement of at least four organ systems, and all have evidence of a marked inflammatory state. Most patients show an increase in the level of at least four inflammatory markers (C-reactive protein, neutrophil count, ferritin, procalcitonin, fibrinogen, interleukin-6, and triglycerides). Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most patients, even those with severe cardiovascular involvement, recover without sequelae. Since coronary aneurysms have been reported, echocardiographic follow-up is needed.", "Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It shares clinical features with Kawasaki disease (KD) and KD shock syndrome. Clinical features include persistent fever, severe illness with involvement of multiple organ systems, and elevated inflammatory markers. Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most children with MIS-C, even those with severe cardiovascular involvement, recover without sequelae. A very similar syndrome has also been reported in adults in association with COVID-19 infection or exposure and is termed multisystem inflammatory syndrome in adults (MIS-A).", "Multisystem inflammatory syndrome in children (MIS-C) is a novel, life-threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This disease has created a diagnostic challenge due to overlap with Kawasaki disease (KD) and KD shock syndrome. The majority of patients with MIS-C present with the involvement of at least four organ systems, and all have evidence of a marked inflammatory state. Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most patients, even those with severe cardiovascular involvement, recover without sequela" ], "type": "summary", "id": "627a989856bf9aee6f000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Recent reports have described a secondary Multisystem Inflammatory Syndrome in Children (MIS-C) after a prior COVID-19 infection that often has features of Kawasaki disease (KD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32631771", "endSection": "abstract" }, { "offsetInBeginSection": 974, "offsetInEndSection": 1225, "text": "In conclusion, multisystem-inflammatory syndrome in children associated with COVID-19 (MIS-C) is a new entity describing a post-infectious inflammatory response in children with prior COVID-19 exposure. Cardiac involvement can include myopericarditis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34509326", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 987, "text": "Multisystem inflammatory syndrome in children (MIS-C) is a novel, life-threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This disease has created a diagnostic challenge due to overlap with Kawasaki disease (KD) and KD shock syndrome. The majority of patients with MIS-C present with the involvement of at least four organ systems, and all have evidence of a marked inflammatory state. Most patients show an increase in the level of at least four inflammatory markers (C-reactive protein, neutrophil count, ferritin, procalcitonin, fibrinogen, interleukin-6, and triglycerides). Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most patients, even those with severe cardiovascular involvement, recover without sequelae. Since coronary aneurysms have been reported, echocardiographic follow-up is needed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34507521", "endSection": "abstract" }, { "offsetInBeginSection": 119, "offsetInEndSection": 381, "text": "Multisystem inflammatory syndrome in children (MIS-C) is a well described and documented condition that is associated with the active or recent COVID-19 infection. A similar presentation in adults is termed as Multisystem inflammatory syndrome in Adults (MIS-A).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34472807", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 563, "text": "A multisystem inflammatory syndrome in children (MIS-C) is a rare but serious complication associated with COVID-19, initiated by an overactive immune response in kids that usually hits weeks after exposure to the COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33679227", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 354, "text": "A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6\u00a0weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32966765", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "The World Health Organization defines the multisystem inflammatory syndrome in children (MIS-C) as a new syndrome reported in patients aged <19 years old who have a history of exposure to SARS-CoV-2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34246424", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Multisystem inflammatory syndrome in children (MIS-C) is a rare and critical condition that affects children following exposure to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, leading to multiorgan dysfunction and shock.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881206", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 234, "text": "Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (COVID-19).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923992", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 357, "text": "SARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33841438", "endSection": "abstract" } ] }, { "body": "What datasets are available related to Duchenne Muscular Dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24634239", "http://www.ncbi.nlm.nih.gov/pubmed/21836521", "http://www.ncbi.nlm.nih.gov/pubmed/23382369", "http://www.ncbi.nlm.nih.gov/pubmed/26356412", "http://www.ncbi.nlm.nih.gov/pubmed/28739181", "http://www.ncbi.nlm.nih.gov/pubmed/32611643", "http://www.ncbi.nlm.nih.gov/pubmed/25338682", "http://www.ncbi.nlm.nih.gov/pubmed/28859693", "http://www.ncbi.nlm.nih.gov/pubmed/30448867", "http://www.ncbi.nlm.nih.gov/pubmed/32692451", "http://www.ncbi.nlm.nih.gov/pubmed/22639722", "http://www.ncbi.nlm.nih.gov/pubmed/33918694", "http://www.ncbi.nlm.nih.gov/pubmed/28807723", "http://www.ncbi.nlm.nih.gov/pubmed/34877803", "http://www.ncbi.nlm.nih.gov/pubmed/19394035", "http://www.ncbi.nlm.nih.gov/pubmed/32791870", "http://www.ncbi.nlm.nih.gov/pubmed/34682100", "http://www.ncbi.nlm.nih.gov/pubmed/26981371", "http://www.ncbi.nlm.nih.gov/pubmed/34776418" ], "ideal_answer": [ "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total).", "MD STARnet, ImagingDMD and PRO-DMD-01 are some of the available DMD datasets.", "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total).", "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)", "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study.", "Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total)." ], "exact_answer": [ [ "MD STARnet", "Muscular Dystrophy Surveillance Tracking and Research Network" ], [ "ImagingDMD" ], [ "PRO-DMD-01" ], [ "PRO051-02" ], [ "D-RSC data", "Duchenne Regulatory Science Consortium database" ], [ "Japanese Registry of Muscular Dystrophy (Remudy)", "Remudy", "Japanese Registry of Muscular Dystrophy" ], [ "GSE38417" ], [ "DuchenneConnect" ], [ "TREAT NMD" ], [ "Muscular Dystrophy Association (MDA)", "MDA Registry", "Muscular Dystrophy Association Registry" ], [ "4D-DMD study" ], [ "Dutch Natural History Survey", "DNHS" ], [ "PPMD", "Parent Project Muscular Dystrophy" ], [ "GSE64420" ], [ "DMD Italian Group" ] ], "type": "list", "id": "6278dd4c56bf9aee6f000011", "snippets": [ { "offsetInBeginSection": 501, "offsetInEndSection": 597, "text": "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34776418", "endSection": "abstract" }, { "offsetInBeginSection": 511, "offsetInEndSection": 735, "text": "Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32611643", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 529, "text": " present study, we have first conducted a meta-analysis of three microarray datasets, GSE38417, GSE3307, and GSE6011, to identify the differentially expressed genes (DEGs) between healthy donors and DMD patients. We have the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33918694", "endSection": "abstract" }, { "offsetInBeginSection": 141, "offsetInEndSection": 425, "text": " The cohort comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), a multistate, multiple-source, population-based surveillance system that identifies and gathers information on all cases of Duchenne and Becker muscular dystrophy born since 1982.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19394035", "endSection": "abstract" }, { "offsetInBeginSection": 472, "offsetInEndSection": 546, "text": "We used the data from the Japanese Registry of Muscular Dystrophy (Remudy)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28859693", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1301, "text": "We report the largest dystrophinopathies mutation dataset in Japan from a national patient registry, \"Remudy\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28859693", "endSection": "abstract" }, { "offsetInBeginSection": 375, "offsetInEndSection": 488, "text": "The gene expression profile dataset GSE38417 of DMD was obtained from the Gene Expression Omnibus (GEO) database.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32791870", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 433, "text": "two microarray data sets obtained from the Gene Expression Omnibus database, we conducted a dysfunctional pathway-enrichment analysis and investigated deregulated genes that are specific to different phases of the disease in order to determine pathogenic characteristics in the progression of DMD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24634239", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 673, "text": "Current methods to monitor DMD patient information (MD STARnet, DuchenneConnect, and TREAT-NMD)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382369", "endSection": "abstract" }, { "offsetInBeginSection": 859, "offsetInEndSection": 968, "text": "A similar patient registry is under development for the Muscular Dystrophy Association (MDA) clinic network. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382369", "endSection": "abstract" }, { "offsetInBeginSection": 90, "offsetInEndSection": 269, "text": "Duchenne Connect patient registry to provide information particularly in regard to active treatment choices in Duchenne muscular dystrophy and their impact on disease progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26356412", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 493, "text": "the case-control 4D-DMD study (Detection by Developmental Delay in Dutch boys with Duchenne Muscular Dystrophy), data on developmental milestones for 76 young males with DMD and 12\u00a0414 young males from a control group were extracted from the health care records of youth health care services. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32692451", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 740, "text": "This study examined three data sets, Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet); Dutch Natural History Survey (DNHS); and Parent Project Muscular Dystrophy (PPMD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28739181", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1444, "text": "The data have been deposited in the Gene Expression Omnibus (GEO) with the accession number GSE64420. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26981371", "endSection": "abstract" }, { "offsetInBeginSection": 1979, "offsetInEndSection": 2037, "text": "escalating dose pilot study (PRO051-02) with drisapersen. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30448867", "endSection": "abstract" }, { "offsetInBeginSection": 1659, "offsetInEndSection": 1706, "text": " in the escalating dose pilot study (PRO051-02)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30448867", "endSection": "abstract" }, { "offsetInBeginSection": 488, "offsetInEndSection": 697, "text": " Data were integrated from past studies through the Duchenne Regulatory Science Consortium (D-RSC) founded by the Critical Path Institute, (15 clinical trials and studies, 1,505 subjects, 27,252 observations).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34877803", "endSection": "abstract" }, { "offsetInBeginSection": 362, "offsetInEndSection": 437, "text": "Using two microarray datasets from Gene Expression Omnibus (GEO) database, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25338682", "endSection": "abstract" } ] }, { "body": "What links immune response pathways to ALS?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27812125", "http://www.ncbi.nlm.nih.gov/pubmed/29568058", "http://www.ncbi.nlm.nih.gov/pubmed/25889790", "http://www.ncbi.nlm.nih.gov/pubmed/32594542", "http://www.ncbi.nlm.nih.gov/pubmed/24170856", "http://www.ncbi.nlm.nih.gov/pubmed/34402459", "http://www.ncbi.nlm.nih.gov/pubmed/20406178", "http://www.ncbi.nlm.nih.gov/pubmed/27308305", "http://www.ncbi.nlm.nih.gov/pubmed/33918092", "http://www.ncbi.nlm.nih.gov/pubmed/25344935" ], "ideal_answer": [ "Microglia, which are the primary immune cells of the central nervous system, are strongly implicated in ALS, their activation being correlated with various clinical features, and inflammatory microglial responses being correlated withe disease progression. The immune response may be implicated in other ways with ALS molecular pathology. such as through inflammatory regulation and circulating interleukins. It is possible the T cell receptor signalling and activation is involved. It is also possible that the innate / non-specific immune system is involved - i.e. immune protection against foreign substances, viruses, and bacteria." ], "type": "summary", "id": "6273a2a0e764a53204000045", "snippets": [ { "offsetInBeginSection": 1469, "offsetInEndSection": 1598, "text": "Neuromuscular pathology in ALS involves the systemic regulation of inflammatory markers mostly active on T-cell immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27308305", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 359, "text": "At the sites of motor neuron injury, accumulation of activated microglia, the primary immune cells of the central nervous system, is commonly observed in both human post mortem studies and animal models of MND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32594542", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 499, "text": "Microglial activation has been found to correlate with many clinical features and importantly, the speed of disease progression in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32594542", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 641, "text": "Both anti-inflammatory and pro-inflammatory microglial responses have been shown to influence disease progression in humans and models of MND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32594542", "endSection": "abstract" }, { "offsetInBeginSection": 652, "offsetInEndSection": 753, "text": "microglia could both contribute to and protect against inflammatory mechanisms of pathogenesis in MND", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32594542", "endSection": "abstract" }, { "offsetInBeginSection": 469, "offsetInEndSection": 664, "text": "ral pathways were found to be upregulated in patients with ALS, among which the toll-like receptor (TLR) and NOD-like receptor (NLR) signaling pathways are related to the immune response. Genes-t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812125", "endSection": "abstract" }, { "offsetInBeginSection": 122, "offsetInEndSection": 319, "text": "he adaptive immune response has been implicated in disease processes of amyotrophic lateral sclerosis (ALS), but it remains unknown if innate immune signaling also contributes to ALS progression. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29568058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "BACKGROUND: The peripheral immune system is implicated in modulating microglial activation, neurodegeneration and disease progression in amyotrophic lateral scle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25889790", "endSection": "abstract" }, { "offsetInBeginSection": 542, "offsetInEndSection": 750, "text": "Besides its connection to inflammation, NF-\u03baB activity can be linked to several genes associated to familial forms of ALS, and many of the environmental risk factors of the disease stimulate NF-\u03baB activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33918092", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1700, "text": "Our data suggest that the TLR and NLR signaling pathways are involved in pathological innate immunity and neuroinflammation associated with ALS and that TOLLIP, MAPK9, IL-1\u03b2, IL-8, and CXCL1 play a role in ALS-specific immune responses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812125", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 656, "text": "Several pathways were found to be upregulated in patients with ALS, among which the toll-like receptor (TLR) and NOD-like receptor (NLR) signaling pathways are related to the immune response.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812125", "endSection": "abstract" }, { "offsetInBeginSection": 1465, "offsetInEndSection": 1701, "text": "Our data suggest that the TLR and NLR signaling pathways are involved in pathological innate immunity and neuroinflammation associated with ALS and that TOLLIP, MAPK9, IL-1\u03b2, IL-8, and CXCL1 play a role in ALS-specific immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27812125", "endSection": "abstract" }, { "offsetInBeginSection": 420, "offsetInEndSection": 746, "text": "Although innate and adaptive immune responses are associated with progressive neurodegeneration, in the early stages of ALS immune activation pathways are primarily considered to be beneficial promoting neuronal repair of the damaged tissues, though a harmful effect of T cells at this stage of disease has also been observed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25344935", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 477, "text": "This includes microglial activation, lymphocyte infiltration, and the induction of C1q, the initiating component of the classic complement system that is the protein-based arm of the innate immune response, in motor neurons of multiple ALS mouse models expressing dismutase active or inactive SOD1 mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170856", "endSection": "abstract" } ] }, { "body": "Which vitamin deficiencies may present with neurologic signs or symptoms?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31838171", "http://www.ncbi.nlm.nih.gov/pubmed/22525460", "http://www.ncbi.nlm.nih.gov/pubmed/21590622", "http://www.ncbi.nlm.nih.gov/pubmed/20402062", "http://www.ncbi.nlm.nih.gov/pubmed/31094486", "http://www.ncbi.nlm.nih.gov/pubmed/33961285", "http://www.ncbi.nlm.nih.gov/pubmed/15142228", "http://www.ncbi.nlm.nih.gov/pubmed/32228659", "http://www.ncbi.nlm.nih.gov/pubmed/6164769", "http://www.ncbi.nlm.nih.gov/pubmed/3722679", "http://www.ncbi.nlm.nih.gov/pubmed/23697293", "http://www.ncbi.nlm.nih.gov/pubmed/31837157", "http://www.ncbi.nlm.nih.gov/pubmed/33231056", "http://www.ncbi.nlm.nih.gov/pubmed/28771404", "http://www.ncbi.nlm.nih.gov/pubmed/24115632", "http://www.ncbi.nlm.nih.gov/pubmed/24365342", "http://www.ncbi.nlm.nih.gov/pubmed/1648656", "http://www.ncbi.nlm.nih.gov/pubmed/6301966", "http://www.ncbi.nlm.nih.gov/pubmed/8682350", "http://www.ncbi.nlm.nih.gov/pubmed/9527151", "http://www.ncbi.nlm.nih.gov/pubmed/6308196", "http://www.ncbi.nlm.nih.gov/pubmed/9012278", "http://www.ncbi.nlm.nih.gov/pubmed/22450609", "http://www.ncbi.nlm.nih.gov/pubmed/26385097", "http://www.ncbi.nlm.nih.gov/pubmed/22303049", "http://www.ncbi.nlm.nih.gov/pubmed/33343698", "http://www.ncbi.nlm.nih.gov/pubmed/23834987", "http://www.ncbi.nlm.nih.gov/pubmed/31193945", "http://www.ncbi.nlm.nih.gov/pubmed/31490402", "http://www.ncbi.nlm.nih.gov/pubmed/3714053", "http://www.ncbi.nlm.nih.gov/pubmed/20640946", "http://www.ncbi.nlm.nih.gov/pubmed/28331457" ], "ideal_answer": [ "Many vitamin deficiencies have been described as a cause of neurologic signs and symptoms. For instance, vitamin B12 deficiency can cause several types of neurological manifestations, such as subacute combined degeneration of the spinal cord, ataxia, peripheral polyneuropathy, optic nerve neuropathy, and cognitive disorders. In addition, vitamin B1 (Thiamine) and B6 (Pyridoxine) deficiency can both cause peripheral neuropathy. Specifically, vitamin B1 deficiency can also cause confusion, ophthalmoplegia, nystagmus, and ataxia in the context of beriberi and Wernicke's encephalopathy. Finally, vitamin A deficiency has been described to cause retinal change-related visual defects and subsequent vision loss." ], "exact_answer": [ [ "Vitamin B12", "Cobalamin" ], [ "Vitamin A" ], [ "Vitamin B1", "Thiamine", "Thiamin" ], [ "Vitamin B6", "Pyridoxine" ], [ "Vitamin E" ], [ "Vitamin D" ] ], "type": "list", "id": "62784f9756bf9aee6f00000a", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 197, "text": "There have been a few reported cases of subacute combined degeneration (SCD) associated with vitamin E deficiency, but the period of intestinal malabsorption was more than several years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31490402", "endSection": "abstract" }, { "offsetInBeginSection": 1528, "offsetInEndSection": 1717, "text": "This case suggests that if neurological symptoms occur in patients with intestinal obstruction, clinicians need to consider a deficiency of micronutrients such as vitamin E and vitamin B12.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31490402", "endSection": "abstract" }, { "offsetInBeginSection": 934, "offsetInEndSection": 1093, "text": "SCD associated with vitamin E deficiency was confirmed by laboratory investigations, electrophysiologic test, and whole spine magnetic resonance imaging scans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31490402", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 346, "text": "Vision loss resulting from thiamine deficiency is a recognized complication of bariatric surgery. Most patients with such vision loss have Wernicke encephalopathy with characteristic changes seen on neuroimaging. Other patients may have retinal hemorrhages, optic disc edema, and peripheral neuropathy without Wernicke encephalopathy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28331457", "endSection": "abstract" }, { "offsetInBeginSection": 928, "offsetInEndSection": 1189, "text": "Patients who undergo bariatric surgery and have a thiamine deficiency can present with visual symptoms and ophthalmologic findings only visible by fundoscopy prior to developing more severe and potentially irreversible complications from the vitamin deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28331457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Children deficient in vitamin E have various neurologic symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8682350", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 446, "text": "A 15-year-old boy with fat malabsorption due to cystic fibrosis who was diagnosed as being vitamin E deficient (< 0.5 mg/l), had typical neuropathies. On the other hand, a 12-year-old Beduin girl had isolated vitamin E deficiency, as well as neurological symptoms suggestive of Friedrich's ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8682350", "endSection": "abstract" }, { "offsetInBeginSection": 1302, "offsetInEndSection": 1663, "text": "The demands in vitamin B12 are particularly high in nervous tissue. Hypovitaminosis is accompanied by pathological lesions both in white and gray brain matter. Several types of neurological manifestations are described: subacute combined degeneration of spinal cord (funicular myelinosis), sensomotor polyneuropathy, optic nerve neuropathy, cognitive disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31094486", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 600, "text": "A 51-year-old female had been on vegetarian diet as a child, and on restrict vegan diet during the last 2 years, developing severe bilateral deterioration of visual function and polyneuropathy. Blood test revealed low levels of vitamin A, B6 and D.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33961285", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 180, "text": "Nutritional visual defects are apparently uncommon nowadays in developed nations. Retinal change-related visual defects caused by hypovitaminoses may be underdiagnosed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33961285", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 519, "text": "Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31837157", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 486, "text": "Epidemiological and clinical data show that the consequences of vitamin D deficiency are relevant to disease risk and can be observed in the progression of many diseases, especially AD, whereas higher serum levels of vitamin D are associated with better cognitive test performance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31838171", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 661, "text": "Multifocal neurological dysfunction in our patient represented beriberi and Wernicke's encephalopathy related to vitamin B1 deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525460", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 326, "text": "We report a 25-year-old woman who developed subacute progressive weakness and areflexia followed by confusion, ophthalmoplegia, and nystagmus following bariatric surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22525460", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Vitamin B12 deficiency is one of the main complications of vegetarianism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231056", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 413, "text": "We describe the case of a 1 month 20 days-old infant who consulted due to paroxysmal episodes of epileptogenic mechanism; laboratory tests identified a deficiency in vitamin B12 as the cause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33231056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Vitamin B12 deficiency is a common cause of neuropsychiatric symptoms in elderly persons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22450609", "endSection": "abstract" }, { "offsetInBeginSection": 1376, "offsetInEndSection": 1715, "text": "Deficiencies of vitamin B 1, B 2 or B 6 were also found in patients with intestinal malabsorption and polyneuropathy, diabetic polyneuropathy, optic atrophy, myelopathy and cerebellar ataxia of unknown etiology, neurological manifestations of neoplasms arising outside the nervous system, B 12 myeloencephalopathy and Th\u00e9venard's syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6164769", "endSection": "abstract" }, { "offsetInBeginSection": 526, "offsetInEndSection": 722, "text": "Thus, individuals with genetic vitamin E deficiency and the familial hypocholesterolemias may develop symptoms of peripheral neuropathy, cerebellar ataxia, and other neurologic signs and symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24365342", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 268, "text": "Symptoms related to vitamin B12 deficiency may be diverse and vary from neurologic to psychiatric.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31193945", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 271, "text": "Wernicke's encephalopathy is a neurologic manifestation of acute thiamine (vitamin B1) deficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33343698", "endSection": "abstract" } ] }, { "body": "Which are the uses of deep learning models in Duchenne Muscular Dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28582264", "http://www.ncbi.nlm.nih.gov/pubmed/32858918", "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "http://www.ncbi.nlm.nih.gov/pubmed/31397906" ], "ideal_answer": [ "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy.", "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy. The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations.", "URL_0 > Deep learning of Ultrasound imaging for evaluation of Ambulatory Function of Individuals with Duchenne Muscular Dystrophy.", "The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations.", "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy. The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations. Deep learning models are used to predict muscle function in DMD patients.", "Deep learning models enable the evaluation of DMD patients using ultrasound images." ], "type": "summary", "id": "6278de8e56bf9aee6f000014", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "title" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1030, "text": "The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "abstract" }, { "offsetInBeginSection": 255, "offsetInEndSection": 379, "text": "udy utilized deep learning of ultrasound imaging for classifying patients with DMD based on their ambulatory function. A tot", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "title" }, { "offsetInBeginSection": 925, "offsetInEndSection": 1047, "text": "hat each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations. The Grad-CAMs in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 373, "text": "This study utilized deep learning of ultrasound imaging for classifying patients with DMD based on their ambulatory function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "abstract" }, { "offsetInBeginSection": 1421, "offsetInEndSection": 1505, "text": "Deep learning of muscle ultrasound is a potential strategy for DMD characterization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy Using Machine Learning.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32858918", "endSection": "title" }, { "offsetInBeginSection": 907, "offsetInEndSection": 1029, "text": "The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Machine Learning to Improve Energy Expenditure Estimation in Children With Disabilities: A Pilot Study in Duchenne Muscular Dystrophy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28582264", "endSection": "title" }, { "offsetInBeginSection": 1403, "offsetInEndSection": 1778, "text": "in children with disabilities (14%-40%). The proposed model for boys with DMD uses ensemble machine learning techniques and gives a 91% correlation with actual measured EE values (root mean square error of 0.017).CONCLUSIONS: Our results confirm that the methods developed to determine EE using accelerometer and heart rate sensor values in normal adults are not appropriate ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28582264", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 783, "text": "\u2009T small-bore scanner. A machine learning approach was used with eight raw quantitative mapping of MRI data images (T1m, T2m, two Dixon maps, and four diffusion tensor imaging maps), three types of texture descriptors (local binary pattern, gray-level co-occurrence matrix, gray-level run-length matrix), and a gradient descriptor (histogram of oriented gradients).RESULTS: The confusion matrix, averaged over all samples, showed 93.5% of mus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31397906", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 663, "text": "A total of 85 individuals (including ambulatory and nonambulatory subjects) underwent ultrasound examinations of the gastrocnemius for deep learning of image data using LeNet, AlexNet, VGG-16, VGG-16TL, VGG-19, and VGG-19TL models (the notation TL indicates fine-tuning pretrained models).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34071811", "endSection": "abstract" } ] }, { "body": "What is \"long-COVID\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34163217", "http://www.ncbi.nlm.nih.gov/pubmed/34580069", "http://www.ncbi.nlm.nih.gov/pubmed/33172844", "http://www.ncbi.nlm.nih.gov/pubmed/34068009", "http://www.ncbi.nlm.nih.gov/pubmed/34024217", "http://www.ncbi.nlm.nih.gov/pubmed/33532785", "http://www.ncbi.nlm.nih.gov/pubmed/33786465", "http://www.ncbi.nlm.nih.gov/pubmed/34276671", "http://www.ncbi.nlm.nih.gov/pubmed/33892403", "http://www.ncbi.nlm.nih.gov/pubmed/34533807", "http://www.ncbi.nlm.nih.gov/pubmed/34709019", "http://www.ncbi.nlm.nih.gov/pubmed/34485849", "http://www.ncbi.nlm.nih.gov/pubmed/34319569" ], "ideal_answer": [ "\"Long-COVID\" is a complex condition where the affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, and the symptoms are not explained by an alternative diagnosis.\n\nPersistent physical symptoms following acute COVID-19 are common and typically include fatigue, dyspnea, chest pain, and cough. Headache, joint pain, myalgias, and loss of smell have also been reported. Common psychological and cognitive symptoms include poor concentration, cognitive impairment/confusion, insomnia, and overall reduced quality of life.", "\"Long COVID\" is the condition whereby affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, whether tested or not. Emerging aspects of the Covid-19 clinical presentation are its long-term effects, which are characteristic of the so-called \"long COVID\". The main symptoms associated with \"long COVID\" were headache, fatigue, muscle aches/myalgia, articular pains, cognitive impairment, loss of concentration, and loss of smell. Additionally, the subjects showed significant levels of insomnia (p < 0.05) and an overall reduced quality of life (p < 0.05). Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings." ], "type": "summary", "id": "62792bb156bf9aee6f00001c", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 165, "text": "While it is now apparent clinical sequelae (long COVID) may persist after acute COVID-19, their nature, frequency and aetiology are poorly characterised.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34580069", "endSection": "abstract" }, { "offsetInBeginSection": 1716, "offsetInEndSection": 2066, "text": "Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34580069", "endSection": "abstract" }, { "offsetInBeginSection": 1252, "offsetInEndSection": 1704, "text": "Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95%\u2009CI 25% to 59%), general malaise (33%; 95%\u2009CI 15% to 57%), fatigue (31%; 95%\u2009CI 24% to 39%), concentration impairment (26%; 95%\u2009CI 21% to 32%) and breathlessness (25%; 95%\u2009CI 18% to 34%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34580069", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 795, "text": "The most frequently reported long-COVID symptoms were mental health-related symptoms (55.2%), fatigue (51.2%), general ache/pain (48.4%), brain fog/confusion (32.8%), and dyspnea (28.9%) among users reporting at least 1 symptom.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34485849", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "\"Long COVID\" is the condition whereby affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, whether tested or not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33786465", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 149, "text": "Emerging aspects of the Covid-19 clinical presentation are its long-term effects, which are characteristic of the so-called \"long COVID\".", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34068009", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 1057, "text": "The main symptoms associated with \"long COVID\" were headache, fatigue, muscle aches/myalgia, articular pains, cognitive impairment, loss of concentration, and loss of smell. Additionally, the subjects showed significant levels of insomnia (p < 0.05) and an overall reduced quality of life (p < 0.05).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34068009", "endSection": "abstract" }, { "offsetInBeginSection": 1224, "offsetInEndSection": 1365, "text": "Further studies are needed in order to better define the clinical presentation of the \"long COVID\" condition and related targeted treatments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34068009", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 266, "text": "'Long-COVID-19' is a term given to the lingering or protracted illness that patients of COVID-19 continue to experience even in their post-recovery phase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34163217", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 867, "text": "Long COVID is defined as four weeks of persisting symptoms after the acute illness, and post-COVID syndrome and chronic COVID-19 are the proposed terms to describe continued symptomatology for more than 12 weeks.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34709019", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 487, "text": "While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34024217", "endSection": "abstract" } ] }, { "body": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22699538", "http://www.ncbi.nlm.nih.gov/pubmed/8347064", "http://www.ncbi.nlm.nih.gov/pubmed/30404418", "http://www.ncbi.nlm.nih.gov/pubmed/32022138", "http://www.ncbi.nlm.nih.gov/pubmed/30688316", "http://www.ncbi.nlm.nih.gov/pubmed/29742798", "http://www.ncbi.nlm.nih.gov/pubmed/22974002", "http://www.ncbi.nlm.nih.gov/pubmed/21954141", "http://www.ncbi.nlm.nih.gov/pubmed/24762862", "http://www.ncbi.nlm.nih.gov/pubmed/31009620", "http://www.ncbi.nlm.nih.gov/pubmed/21800026", "http://www.ncbi.nlm.nih.gov/pubmed/28084836", "http://www.ncbi.nlm.nih.gov/pubmed/16102988", "http://www.ncbi.nlm.nih.gov/pubmed/31879850", "http://www.ncbi.nlm.nih.gov/pubmed/29174526", "http://www.ncbi.nlm.nih.gov/pubmed/31546754", "http://www.ncbi.nlm.nih.gov/pubmed/32390640", "http://www.ncbi.nlm.nih.gov/pubmed/30180785", "http://www.ncbi.nlm.nih.gov/pubmed/34155911", "http://www.ncbi.nlm.nih.gov/pubmed/29167533" ], "ideal_answer": [ "North Star Ambulatory Assessment is practical and reliable. allow assessment of high-functioning boys with Duchenne muscular dystrophy.", "Yes, functional tests are a good biomarker for Duchenne Muscular Dystrophy. \nNorth Star Ambulatory Assessment is practical and reliable. allow assessment of high-functioning boys with Duchenna muscular dystrophy \nFunctional tests are used for assessment of boys with muscular atrophy.", "Functional tests such as North Star Ambulatory Assessment (NSAA) are good biomarkers for Duchenne Muscular Dystrophy.", "North Star Ambulatory Assessment is practical and reliable.", "allow assessment of high-functioning boys with Duchenne muscular dystrophy.North Star Ambulatory Assessment is practical and reliable." ], "exact_answer": "yes", "type": "yesno", "id": "6278ddfe56bf9aee6f000013", "snippets": [ { "offsetInBeginSection": 934, "offsetInEndSection": 993, "text": "North Star Ambulatory Assessment is practical and reliable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21954141", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1195, "text": "allow assessment of high-functioning boys with Duchenne muscular dystrophy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21954141", "endSection": "abstract" }, { "offsetInBeginSection": 536, "offsetInEndSection": 804, "text": "agnosis and tracking of symptom progression of DMD usually relies on creatine kinase tests, evaluation of patient performance in various ambulatory assessments, and detection of dystrophin from muscle biopsies, which are invasive and painful for the patient. While the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31546754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Aim: Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments of thigh muscle. Patients & methods: Analysis included timed functional tests, knee extension/strength and North St", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "A New Functional Scale and Ambulatory Functional Classification of Duchenne Muscular Dystrophy: Scale Development and Preliminary Analyses of Reliability and Validity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404418", "endSection": "title" }, { "offsetInBeginSection": 151, "offsetInEndSection": 450, "text": "his preliminary investigation describes the relationship between community ambulation measured by the StepWatch activity monitor and the current standard of functional assessment, the 6-minute walk test, in ambulatory boys with Duchenne muscular dystrophy (n = 16) and healthy controls (n = 13). All", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24762862", "endSection": "abstract" }, { "offsetInBeginSection": 553, "offsetInEndSection": 860, "text": "ith strength assessments. MV index, fat fraction and T2-mapping measures had moderate correlations (r \u223c\u00a00.5) to all functional tests, North Star Ambulatory Assessment and age. Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155911", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 560, "text": "on with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6\u2009minute walk test (6MWT) is paramount for biomarker qualification. In this stu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29167533", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22974002", "endSection": "title" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1088, "text": "The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30688316", "endSection": "abstract" }, { "offsetInBeginSection": 729, "offsetInEndSection": 897, "text": "Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenne muscular dystrophy clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155911", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 567, "text": "Currently, functional measures continue to serve as the primary outcome for the majority of DMD clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31879850", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 325, "text": "Patients & methods: Analysis included timed functional tests, knee extension/strength and North Star\u00a0Ambulatory Assessment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155911", "endSection": "abstract" }, { "offsetInBeginSection": 861, "offsetInEndSection": 1089, "text": "The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30688316", "endSection": "abstract" }, { "offsetInBeginSection": 1305, "offsetInEndSection": 1603, "text": "We have developed a new scale and the associated classification system, to assess the functional ability of children diagnosed with DMD. Preliminary evaluation of the psychometric properties of the functional scale and classification systems indicate sufficient reliability and concurrent validity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30404418", "endSection": "abstract" }, { "offsetInBeginSection": 1090, "offsetInEndSection": 1518, "text": "Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30688316", "endSection": "abstract" }, { "offsetInBeginSection": 458, "offsetInEndSection": 673, "text": "The children's functional performance was assessed using 6-minute walk tests and timed performance tests. The correlations between the flexibilities of the lower limb muscles and the performance tests were examined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30180785", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 1075, "text": "The flexibilities of the lower extremity muscles were found to be correlated to the 6-minute walk tests and the timed performance tests. The flexibility of the hamstrings (r\u2009=\u2009-.825), the gastrocnemius muscles (r\u2009=\u2009.545), the hip flexors (r\u2009=\u2009.481), and the tensor fascia latae (r\u2009=\u2009.445) were found to be correlated with functional performance as measured by the 6-minute walk tests (P\u2009<\u2009.05)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30180785", "endSection": "abstract" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1776, "text": "Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32390640", "endSection": "abstract" }, { "offsetInBeginSection": 1130, "offsetInEndSection": 1353, "text": " In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29174526", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 464, "text": " This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22974002", "endSection": "abstract" }, { "offsetInBeginSection": 788, "offsetInEndSection": 985, "text": "The MFM scale was a useful instrument in the follow up of patients with DMD. Moreover, it is a more comprehensive scale to assess patients and very good for conducting trials to evaluate treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22699538", "endSection": "abstract" }, { "offsetInBeginSection": 500, "offsetInEndSection": 636, "text": "MD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6\u00a0min walk test (6MWT) and 10\u00a0m walk.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21800026", "endSection": "abstract" }, { "offsetInBeginSection": 776, "offsetInEndSection": 891, "text": "TFTs appear to be slightly more responsive and predictive of disease progression than the 6MWT in 7-12.9 year olds.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29742798", "endSection": "abstract" }, { "offsetInBeginSection": 1029, "offsetInEndSection": 1401, "text": "herefore, in our group of ambulant patients with DMD, timed functional testing was the most sensitive parameter to determine the extent of disease progression. Timed functional testing may therefore be considered as an additional outcome measure in drug trials to evaluate the effects of therapy in ambulant patients with DMD and possibly in other neuromuscular disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16102988", "endSection": "abstract" }, { "offsetInBeginSection": 1626, "offsetInEndSection": 1747, "text": "Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31009620", "endSection": "abstract" }, { "offsetInBeginSection": 452, "offsetInEndSection": 718, "text": "he muscle strength of the wrist extensors and the radial deviation range of motion at the wrist were found to be strongly correlated with six of the seven tasks assessed. These two clinical assessments appear to be good indicators of overall wrist and hand function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8347064", "endSection": "abstract" } ] }, { "body": "What is the most sensitive test for the diagnosis of multiple sclerosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16400831", "http://www.ncbi.nlm.nih.gov/pubmed/10919200", "http://www.ncbi.nlm.nih.gov/pubmed/3208208", "http://www.ncbi.nlm.nih.gov/pubmed/20003089", "http://www.ncbi.nlm.nih.gov/pubmed/6830166", "http://www.ncbi.nlm.nih.gov/pubmed/7629529", "http://www.ncbi.nlm.nih.gov/pubmed/1449838", "http://www.ncbi.nlm.nih.gov/pubmed/2795066", "http://www.ncbi.nlm.nih.gov/pubmed/8164014" ], "ideal_answer": [ "These results support previous conclusions that MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS.", "MRI is the most sensitive tool for the diagnosis of multiple sclerosis (MS). It can detect asymptomatic lesions in the white matter and is the most predictive test for diagnosing clinically definite multiple sclerosis (CDMS). It is also a reliable measure of the current disease activity. The presence of oligoclonal bands in the cerebrospinal fluid (CSF) provides supportive evidence for the diagnosis of MS.", "MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS. MRI also is a reliable measure of the extent of the MS process, serial MRI scans detect evidence of disease activity in MS not always disclosed by clinical evaluation. Results indicate that the presence of oligoclonal bands provides sensitive supporting evidence" ], "exact_answer": [ "Magnetic resonance imaging", "MRI", "MR" ], "type": "factoid", "id": "6277de0d56bf9aee6f000006", "snippets": [ { "offsetInBeginSection": 704, "offsetInEndSection": 843, "text": "The initial MRI was strongly suggestive of MS in 19 of these (68%), while 27 (96%) had at least one MS-like abnormality in the initial MRI.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8164014", "endSection": "abstract" }, { "offsetInBeginSection": 1059, "offsetInEndSection": 1237, "text": "These results support previous conclusions that MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8164014", "endSection": "abstract" }, { "offsetInBeginSection": 639, "offsetInEndSection": 863, "text": "The most sensitive test was MRI (93%) followed by VEP (83%) and BAEP (60%) and the sensitivity of the study with high resolution CT including 59 patients explored by double enhancement and delayed cut off was very low (33%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1449838", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 305, "text": " In diagnosis, MRI is the most sensitive test for the demonstration of dissemination of lesions in space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3208208", "endSection": "abstract" }, { "offsetInBeginSection": 508, "offsetInEndSection": 675, "text": "MRI also is a reliable measure of the extent of the MS process, serial MRI scans detect evidence of disease activity in MS not always disclosed by clinical evaluation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3208208", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1591, "text": "These results indicate that the presence of oligoclonal bands provides sensitive supporting evidence for the diagnosis of MS but that bands may be present in other disorders, including those not directly related to infection or abnormal immune response. The data suggest that oligoclonal bands may represent an immune response to neurological injury that is prominent in disorders with a particularly intense or continuous antigenic stimulus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6830166", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Magnetic resonance imaging (MRI) has recently been recognised as the most sensitive method with which to detect clinically silent lesions in patients affected by multiple sclerosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2795066", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Magnetic resonance imaging (MRI) is a sensitive paraclinical test for diagnosis and assessment of disease progression in multiple sclerosis (MS) and is often used to evaluate therapeutic efficacy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20003089", "endSection": "abstract" } ] }, { "body": "Define pseudotumor cerebri. How is it treated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23265564", "http://www.ncbi.nlm.nih.gov/pubmed/8721925", "http://www.ncbi.nlm.nih.gov/pubmed/10529973", "http://www.ncbi.nlm.nih.gov/pubmed/23136035", "http://www.ncbi.nlm.nih.gov/pubmed/27128512", "http://www.ncbi.nlm.nih.gov/pubmed/32736880", "http://www.ncbi.nlm.nih.gov/pubmed/11524298", "http://www.ncbi.nlm.nih.gov/pubmed/11240545", "http://www.ncbi.nlm.nih.gov/pubmed/25449933", "http://www.ncbi.nlm.nih.gov/pubmed/2347863", "http://www.ncbi.nlm.nih.gov/pubmed/29393752", "http://www.ncbi.nlm.nih.gov/pubmed/26444398", "http://www.ncbi.nlm.nih.gov/pubmed/10532364", "http://www.ncbi.nlm.nih.gov/pubmed/11680122", "http://www.ncbi.nlm.nih.gov/pubmed/7049034", "http://www.ncbi.nlm.nih.gov/pubmed/3799419", "http://www.ncbi.nlm.nih.gov/pubmed/20721668", "http://www.ncbi.nlm.nih.gov/pubmed/1614156", "http://www.ncbi.nlm.nih.gov/pubmed/33717740", "http://www.ncbi.nlm.nih.gov/pubmed/16388155", "http://www.ncbi.nlm.nih.gov/pubmed/15010717" ], "ideal_answer": [ "Benign intracranial hypertension (BIH) is characterized by an elevation of the intracranial pressure not associated with an intracranial process or hydrocephaly, and with normal cerebrospinal fluid (CSF) contents. The elevation of the intracranial pressure is isolated; therefore, diseases such as cerebral venous thrombosis or dural fistulas should not be considered as etiologies of BIH. The exact definition of BIH remains debated, and other terms such as \"pseudotumor cerebri\" or \"idiopathic intracranial hypertension\" are often used in the literature. The management of patients with BIH depends mainly on the presence and severity of ocular symptoms and signs on which the prognostic of the disease is based. Repeated lumbar punctures associated with acetazolamide and weight loss are usually efficient enough. However a surgical treatment (optic nerve sheath fenestration or lumboperitoneal shunt) is required when appropriate medical management does not prevent progressive alteration of vision (visual loss or visual field defect), or when the patients complains of severe, refractory headaches. Careful follow-up with repeated formal visual field testing may help preventing a devastating visual loss in these patients.", "Pseudotumor cerebri is a condition characterized by an elevation of the intracranial pressure not associated with an intracranial process or hydrocephaly, and with normal cerebrospinal fluid (CSF) contents. It most often occurs in obese women of childbearing age. The management of patients with pseudotumor cerebri mainly depends on the presence and severity of ocular symptoms and signs on which the prognostic of the disease is based. Repeated lumbar punctures associated with acetazolamide and weight loss are usually efficient enough. However a surgical treatment (optic nerve sheath fenestration or lumboperitoneal shunt) is required when appropriate medical management does not prevent progressive alteration of vision (visual loss or visual field defect), or when the patients complains of severe, refractory headaches. Careful follow-up with repeated formal visual field testing may help preventing a devastating visual loss in these patients." ], "type": "summary", "id": "627aa17156bf9aee6f000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 556, "text": "Benign intracranial hypertension (BIH) is characterized by an elevation of the intracranial pressure not associated with an intracranial process or hydrocephaly, and with normal cerebrospinal fluid (CSF) contents. The elevation of the intracranial pressure is isolated; therefore, diseases such as cerebral venous thrombosis or dural fistulas should not be considered as etiologies of BIH. The exact definition of BIH remains debated, and other terms such as \"pseudotumor cerebri\" or \"idiopathic intracranial hypertension\" are often used in the literature.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11240545", "endSection": "abstract" }, { "offsetInBeginSection": 985, "offsetInEndSection": 1657, "text": "The management of patients with BIH depends mainly on the presence and severity of ocular symptoms and signs on which the prognostic of the disease is based. Repeated lumbar punctures associated with acetazolamide and weight loss are usually efficient enough. However a surgical treatment (optic nerve sheath fenestration or lumboperitoneal shunt) is required when appropriate medical management does not prevent progressive alteration of vision (visual loss or visual field defect), or when the patients complains of severe, refractory headaches. Careful follow-up with repeated formal visual field testing may help preventing a devastating visual loss in these patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11240545", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Idiopathic intracranial hypertension (IIH) is a rare disorder occurring more frequently in obese women of childbearing age, resulting in increased intracranial pressure (ICP) from an unknown cause.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26444398", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Pseudotumor cerebri is a disorder characterized by increased intracranial pressure that predominantly affects obese young women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32736880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Pseudotumor cerebri is characterized by increased intracranial pressure and papilledema, with an essentially normal neurologic examination", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3799419", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Pseudotumor cerebri is a central nervous disorder with elevated intracranial pressure that is most common among young obese women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1614156", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Pseudotumor cerebri is an unusual syndrome of increased intracranial pressure without a space-occupying mass.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10529973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Pseudotumor cerebri is an idiopathic disorder characterized by papilledema and elevated intracranial pressure without a mass lesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15010717", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Pseudotumor cerebri, or benign intracranial hypertension, is characterized by intracranial hypertension of unknown etiology typically in obese women <45 years of age, and can be disabling secondary to headaches and visual disturbances.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23265564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Pseudotumor cerebri is a clinical syndrome characterized by raised intracranial pressure with normal ventricular size, anatomy and position.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16388155", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 345, "text": "Pseudotumor cerebri is a poorly understood syndrome characterized by chronic headaches, bilateral papilledema, and increased intracranial pressure without localized neurologic signs or symptoms, intracranial mass, or hydrocephalus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2347863", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 202, "text": "Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is a complex and difficult-to-manage condition that can lead to permanent vision loss and refractory headaches if untreated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29393752", "endSection": "abstract" } ] }, { "body": "What is pseudodementia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21995351", "http://www.ncbi.nlm.nih.gov/pubmed/7316680", "http://www.ncbi.nlm.nih.gov/pubmed/23979551", "http://www.ncbi.nlm.nih.gov/pubmed/9658274", "http://www.ncbi.nlm.nih.gov/pubmed/453349", "http://www.ncbi.nlm.nih.gov/pubmed/6342420", "http://www.ncbi.nlm.nih.gov/pubmed/3911280", "http://www.ncbi.nlm.nih.gov/pubmed/30319082", "http://www.ncbi.nlm.nih.gov/pubmed/2204977", "http://www.ncbi.nlm.nih.gov/pubmed/12910854", "http://www.ncbi.nlm.nih.gov/pubmed/32318620", "http://www.ncbi.nlm.nih.gov/pubmed/4050642" ], "ideal_answer": [ "Depression can cause some clinical symptoms and signs of dementia, classically in older adults. This type of \"dementia\" is called pseudodementia and is typically reversible with treatment.", "Pseudodementia is defined as an intellectual impairment in patients with a primary psychiatric disorder, in which the features of intellectual abnormality resemble, at least in part, those of a neuropathologically induced cognitive deficit. This neuropsychological impairment is reversible, and there is no apparent primary neuropathological process that leads to the genesis of this disturbance." ], "type": "summary", "id": "6277d7f356bf9aee6f000004", "snippets": [ { "offsetInBeginSection": 121, "offsetInEndSection": 505, "text": "It is defined as an intellectual impairment in patients with a primary psychiatric disorder, in which the features of intellectual abnormality resemble, at least in part, those of a neuropathologically induced cognitive deficit. This neuropsychological impairment is reversible, and there is no apparent primary neuropathological process that leads to the genesis of this disturbance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7316680", "endSection": "abstract" }, { "offsetInBeginSection": 1251, "offsetInEndSection": 1769, "text": "A new definition has been introduced for 'pseudodementia' as a syndrome of reversible subjective or objective cognitive problems caused by non-organic disorder. Thus depressive pseudodementia may be classified into two subtypes. Type I is a group of patients who have depressive symptoms with subject complaint of dysmnesia without measurable intellectual deficits. Type II is a group of patients who have depressive symptoms and show poor cognitive performance based on poor concentration not due to organic disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9658274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 265, "text": "Dementia has a wide range of reversible causes. Well known among these is depression, though other psychiatric disorders can also impair cognition and give the appearance of neurodegenerative disease. This phenomenon has been known historically as \"pseudodementia.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32318620", "endSection": "abstract" }, { "offsetInBeginSection": 361, "offsetInEndSection": 646, "text": "The term \"pseudodementia\" had been used previously. However, Kiloh's paper gave impetus to psychiatrists to focus on the potential reversibility of cognitive impairments that might be attributable to psychiatric disorders (depression, schizophrenia and conversion disorder among them).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21995351", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 239, "text": "Cognitive dysfunctions in elder depressive patients (so called pseudodementia) as well as comorbidity of dementia with depression are special diagnostic problems.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12910854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "The most common features of cognitive impairment due to pseudodementia are a relatively acute onset, symptoms of six to 12 months duration; past psychiatric history, particularly depressive illness; age over 50; frequent \"don't know\" as opposed to \"near miss\" answers; normal electroencephalogram and computed tomographic scan of the brain, and absence of nocturnal worsening. With this ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4050642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Depressive pseudodementia is a major depressive disorder in which the cognitive deficits secondary to the affective disorder is so significant that clinicians are obliged to consider dementia as a differential diagnosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23979551", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 229, "text": "Despite the increased attention that the syndrome of pseudodementia is receiving, several important questions regarding diagnostic criteria and accuracy, etiology, and even the appropriateness of the term itself remain unanswered", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6342420", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Pseudodementia is the syndrome in which dementia is mimicked or caricatured by functional psychiatric disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/453349", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "The term pseudodementia is applied to the range of functional psychiatric conditions such as depression, schizophrenia and hysteria that may mimic organic dementia, but are essentially reversible on treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3911280", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "The concept of pseudodementia was coined in the late XIXth century to refer to a syndrome mimicking dementia, but without underlying neurological lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2204977", "endSection": "abstract" } ] }, { "body": "Should acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) be used when providing supportive care for COVID-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32805057", "http://www.ncbi.nlm.nih.gov/pubmed/33824640", "http://www.ncbi.nlm.nih.gov/pubmed/34318916", "http://www.ncbi.nlm.nih.gov/pubmed/33135113", "http://www.ncbi.nlm.nih.gov/pubmed/33658615", "http://www.ncbi.nlm.nih.gov/pubmed/32447629", "http://www.ncbi.nlm.nih.gov/pubmed/34339037", "http://www.ncbi.nlm.nih.gov/pubmed/32256706", "http://www.ncbi.nlm.nih.gov/pubmed/32460369", "http://www.ncbi.nlm.nih.gov/pubmed/33997800", "http://www.ncbi.nlm.nih.gov/pubmed/33197762", "http://www.ncbi.nlm.nih.gov/pubmed/32505846" ], "ideal_answer": [ "Nonsteroidal anti-inflammatory drugs (NSAIDs) have been theorized to cause harm in patients with COVID-19, but clinical data are limited. Given the uncertainty, acetaminophen is the preferred antipyretic agent for most patients rather than NSAIDs. If NSAIDs are needed, the lowest effective dose is recommended.", "Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID-19 and case-reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID-19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID-19 patients until there are enough evidence." ], "exact_answer": [ "Acetaminophen", "Paracetamol" ], "type": "factoid", "id": "6277e4ee56bf9aee6f000008", "snippets": [ { "offsetInBeginSection": 1136, "offsetInEndSection": 1676, "text": "Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID-19 and case-reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID-19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID-19 patients until there are enough evidence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32460369", "endSection": "abstract" }, { "offsetInBeginSection": 1230, "offsetInEndSection": 1503, "text": "Pharmacological approaches like acetaminophen, NSAIDS, spasmolytics etc. can be used if non-pharmacological therapy is inadequate. As per the current strength of evidence, acetaminophen and ibuprofen can be safely administered for pain management in children with COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33824640", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 364, "text": "Recently, the safety of ibuprofen in COVID-19 patients has been questioned due to anecdotal reports of worsening symptoms in previously healthy young adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32505846", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1401, "text": "Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses. There are clearly COVID-19 cases where NSAIDs should not be used, but there is no strong evidence that NSAIDs must be avoided in all patients with COVID-19; clinicians must weigh these choices on an individual basis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32447629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 322, "text": "Concern about the appropriate role of nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 speculate that NSAIDs, in particular ibuprofen, may upregulate the entry point for the virus, the angiotensin-converting enzyme (ACE)\u00a02 receptors and increase susceptibility to the virus or worsen symptoms in existing disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32447629", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 717, "text": "The Expert Working Group on the Commission of Human Medicines in the UK and other organizations have stated that there is insufficient evidence to establish a link between ibuprofen and susceptibility to or exacerbation of COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32447629", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 471, "text": "To provide analgesia, paracetamol can be listed as the first option in these patients, and then NSAIDs can also be reliably used for pain management in patients with COVID-19 if there are no absolute contraindications such as kidney failure or gastric bleeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34318916", "endSection": "abstract" }, { "offsetInBeginSection": 1185, "offsetInEndSection": 1401, "text": "There are clearly COVID-19 cases where NSAIDs should not be used, but there is no strong evidence that NSAIDs must be avoided in all patients with COVID-19; clinicians must weigh these choices on an individual basis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32447629", "endSection": "abstract" }, { "offsetInBeginSection": 1055, "offsetInEndSection": 1183, "text": "Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32447629", "endSection": "abstract" } ] }, { "body": "Is there a way to distinguish COVID-19 clinically from other respiratory illnesses, particularly influenza?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33135801", "http://www.ncbi.nlm.nih.gov/pubmed/32542934", "http://www.ncbi.nlm.nih.gov/pubmed/32881022", "http://www.ncbi.nlm.nih.gov/pubmed/33537361", "http://www.ncbi.nlm.nih.gov/pubmed/32856744", "http://www.ncbi.nlm.nih.gov/pubmed/33742041", "http://www.ncbi.nlm.nih.gov/pubmed/34016193", "http://www.ncbi.nlm.nih.gov/pubmed/32903584", "http://www.ncbi.nlm.nih.gov/pubmed/32445165" ], "ideal_answer": [ "No, the clinical features of COVID-19 overlap substantially with influenza and other respiratory viral illnesses. There is no way to distinguish among them without testing.", "Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations)", "Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations). At present, clinical workup of COVID-19 remains a hard task to accomplish." ], "exact_answer": "no", "type": "yesno", "id": "627926bc56bf9aee6f00001a", "snippets": [ { "offsetInBeginSection": 166, "offsetInEndSection": 410, "text": "Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33537361", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 967, "text": "Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32445165", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 1017, "text": "In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32881022", "endSection": "abstract" }, { "offsetInBeginSection": 135, "offsetInEndSection": 249, "text": "COVID-19 has a similar pattern of infection, clinical symptoms, and chest imaging findings to influenza pneumonia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33742041", "endSection": "abstract" }, { "offsetInBeginSection": 354, "offsetInEndSection": 573, "text": "Here, we hypothesize the order of symptom occurrence could help patients and medical professionals more quickly distinguish COVID-19 from other respiratory diseases, yet such essential information is largely unavailable", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32903584", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "It is difficult to distinguish coronavirus disease-2019 (COVID-19) from other viral respiratory tract infections owing to the similarities in clinical and radiological findings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33135801", "endSection": "abstract" } ] }, { "body": "What is the incubation period for COVID-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34579681", "http://www.ncbi.nlm.nih.gov/pubmed/34131198", "http://www.ncbi.nlm.nih.gov/pubmed/33998486", "http://www.ncbi.nlm.nih.gov/pubmed/34368314", "http://www.ncbi.nlm.nih.gov/pubmed/33915459", "http://www.ncbi.nlm.nih.gov/pubmed/34485577", "http://www.ncbi.nlm.nih.gov/pubmed/34117868", "http://www.ncbi.nlm.nih.gov/pubmed/33548553", "http://www.ncbi.nlm.nih.gov/pubmed/33035373", "http://www.ncbi.nlm.nih.gov/pubmed/32627172", "http://www.ncbi.nlm.nih.gov/pubmed/34886835", "http://www.ncbi.nlm.nih.gov/pubmed/33643779", "http://www.ncbi.nlm.nih.gov/pubmed/33748041", "http://www.ncbi.nlm.nih.gov/pubmed/33024342", "http://www.ncbi.nlm.nih.gov/pubmed/34541481", "http://www.ncbi.nlm.nih.gov/pubmed/33706702", "http://www.ncbi.nlm.nih.gov/pubmed/32848488", "http://www.ncbi.nlm.nih.gov/pubmed/34535192", "http://www.ncbi.nlm.nih.gov/pubmed/33818217", "http://www.ncbi.nlm.nih.gov/pubmed/32594928", "http://www.ncbi.nlm.nih.gov/pubmed/34423821", "http://www.ncbi.nlm.nih.gov/pubmed/33832511", "http://www.ncbi.nlm.nih.gov/pubmed/33362233", "http://www.ncbi.nlm.nih.gov/pubmed/33773195", "http://www.ncbi.nlm.nih.gov/pubmed/32801208", "http://www.ncbi.nlm.nih.gov/pubmed/32661509" ], "ideal_answer": [ "For COVID-19, the mean incubation period was 6.0\u00a0days globally but near 7.0\u00a0days in the mainland of China, which will help identify the time of infection and make disease control decisions. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain.", "The incubation period for COVID-19 is thought to be within 14 days following exposure, with most cases occurring approximately five to seven days after exposure. The incubation period also varies by viral variant. For example, the incubation period for the Delta variant (B.1.617.2) appears to be slightly shorter, with symptoms first appearing around four days after exposure." ], "exact_answer": [ "5-7 days", "5 days", "6 days", "7 days" ], "type": "factoid", "id": "6277e52256bf9aee6f000009", "snippets": [ { "offsetInBeginSection": 1199, "offsetInEndSection": 1304, "text": "We find that the incubation period has a median of 8.50\u00a0days (95% confidence interval [CI] [7.22; 9.15]).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32627172", "endSection": "abstract" }, { "offsetInBeginSection": 829, "offsetInEndSection": 1256, "text": "The pooled mean incubation period of COVID-19 was 6.0\u00a0days (95% confidence interval [CI] 5.6-6.5) globally, 6.5\u00a0days (95% CI 6.1-6.9) in the mainland of China, and 4.6\u00a0days (95% CI 4.1-5.1) outside the mainland of China (P\u2009=\u20090.006). The incubation period varied with age (P\u2009=\u20090.005). Meanwhile, in 11 545 patients, the mean incubation period was 7.1\u00a0days (95% CI 7.0-7.2), which was similar to the finding in our meta-analysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535192", "endSection": "abstract" }, { "offsetInBeginSection": 1269, "offsetInEndSection": 1458, "text": "For COVID-19, the mean incubation period was 6.0\u00a0days globally but near 7.0\u00a0days in the mainland of China, which will help identify the time of infection and make disease control decisions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535192", "endSection": "abstract" }, { "offsetInBeginSection": 1009, "offsetInEndSection": 1256, "text": "The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33024342", "endSection": "abstract" }, { "offsetInBeginSection": 823, "offsetInEndSection": 1101, "text": "The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34541481", "endSection": "abstract" }, { "offsetInBeginSection": 1429, "offsetInEndSection": 1531, "text": "We estimated that the 0.95-th quantile related to people in the age group 23 \u223c55 is less than 15 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34579681", "endSection": "abstract" }, { "offsetInBeginSection": 1129, "offsetInEndSection": 1260, "text": "Based on the collected data, we found that the conditional quantiles of the incubation period distribution of COVID-19 vary by age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34579681", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 581, "text": "The estimated mean incubation period we obtain is 6.74 days (95% Confidence Interval(CI): 6.35 to 7.13), and the 90th percentile is 11.64 days (95% CI: 11.22 to 12.17), corresponding to a good agreement with statistical supported studies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34131198", "endSection": "abstract" }, { "offsetInBeginSection": 693, "offsetInEndSection": 921, "text": "The mean and median incubation period were of maximum 8 days and 12 days respectively. In various parametric models, the 95th percentiles were in the range 10.3-16 days. The highest 99th percentile would be as long as 20.4 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33832511", "endSection": "abstract" }, { "offsetInBeginSection": 1260, "offsetInEndSection": 1356, "text": "The mean incubation period ranged from 5.2 (95% CI 4.4 to 5.9) to 6.65 days (95% CI 6.0 to 7.2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33832511", "endSection": "abstract" }, { "offsetInBeginSection": 1369, "offsetInEndSection": 1569, "text": "This work provides additional evidence of incubation period for COVID-19 and showed that it is prudent not to dismiss the possibility of incubation periods up to 14 days at this stage of the epidemic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33832511", "endSection": "abstract" }, { "offsetInBeginSection": 311, "offsetInEndSection": 455, "text": "For COVID-19, average incubation period times commonly span 5-7 days which are generally longer than for most typical other respiratory viruses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33915459", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 902, "text": "Our estimated median incubation period of COVID-19 is 5.4 days (bootstrapped 95% confidence interval (CI) 4.8-6.0), and the 2.5th and 97.5th percentiles are 1 and 15 days, respectively; while the estimated serial interval of COVID-19 falls within the range of -4 to 13 days with 95% confidence and has a median of 4.6 days (95% CI 3.7-5.5).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32594928", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 504, "text": "We conducted a systematic review and meta-analysis on published estimates of the incubation period distribution of COVID-19, and showed that the pooled median of the point estimates of the mean, median and 95 th percentile for incubation period are 6.3 days (range: 1.8 to 11.9 days), 5.4 days (range: 2.0 to 17.9 days) and 13.1 days (range: 3.2 to 17.8 days) respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34117868", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 981, "text": "The incubation period in COVID-19 (6.4 days estimated) was longer than influenza type A (3.4 days).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33035373", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 407, "text": "Children (aged below 18 years) are susceptible to COVID-19, with an average incubation period of about 6.5 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33748041", "endSection": "abstract" }, { "offsetInBeginSection": 363, "offsetInEndSection": 601, "text": "At present, the quarantine duration in most countries is 14 d due to the fact that the incubation period of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is usually identified as 1-14 d with median estimate of 4-7.5 d.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34368314", "endSection": "abstract" }, { "offsetInBeginSection": 818, "offsetInEndSection": 1024, "text": "The median COVID-19 incubation period was 8.3 (90% confidence interval [CI], 7.4-9.2) days for all patients, 7.6 (90% CI, 6.7-8.6) days for younger adults, and 11.2 (90% CI, 9.0-13.5) days for older adults.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32661509", "endSection": "abstract" }, { "offsetInBeginSection": 1151, "offsetInEndSection": 1255, "text": "This analysis provides evidence for an average incubation period for COVID-19 of approximately 6.4 days.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33362233", "endSection": "abstract" } ] }, { "body": "What is Guillain-Barre syndrome (GBS)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33002998", "http://www.ncbi.nlm.nih.gov/pubmed/26560944", "http://www.ncbi.nlm.nih.gov/pubmed/30895887", "http://www.ncbi.nlm.nih.gov/pubmed/24872655", "http://www.ncbi.nlm.nih.gov/pubmed/15168961", "http://www.ncbi.nlm.nih.gov/pubmed/20508277", "http://www.ncbi.nlm.nih.gov/pubmed/32537271", "http://www.ncbi.nlm.nih.gov/pubmed/26793497", "http://www.ncbi.nlm.nih.gov/pubmed/9365863", "http://www.ncbi.nlm.nih.gov/pubmed/23117942", "http://www.ncbi.nlm.nih.gov/pubmed/19202218", "http://www.ncbi.nlm.nih.gov/pubmed/12134330", "http://www.ncbi.nlm.nih.gov/pubmed/23642721", "http://www.ncbi.nlm.nih.gov/pubmed/24731000", "http://www.ncbi.nlm.nih.gov/pubmed/31639842", "http://www.ncbi.nlm.nih.gov/pubmed/16708185", "http://www.ncbi.nlm.nih.gov/pubmed/8478553", "http://www.ncbi.nlm.nih.gov/pubmed/12690329", "http://www.ncbi.nlm.nih.gov/pubmed/23431480", "http://www.ncbi.nlm.nih.gov/pubmed/30069105", "http://www.ncbi.nlm.nih.gov/pubmed/23087283", "http://www.ncbi.nlm.nih.gov/pubmed/15018590", "http://www.ncbi.nlm.nih.gov/pubmed/24511391", "http://www.ncbi.nlm.nih.gov/pubmed/28968363", "http://www.ncbi.nlm.nih.gov/pubmed/16206698", "http://www.ncbi.nlm.nih.gov/pubmed/12415961", "http://www.ncbi.nlm.nih.gov/pubmed/15921641", "http://www.ncbi.nlm.nih.gov/pubmed/34434441", "http://www.ncbi.nlm.nih.gov/pubmed/32192609" ], "ideal_answer": [ "Guillain-Barr\u00e9 syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF). Recently, the heterogeneity of GBS has been noticed with definition of several GBS variants. The diagnosis of GBS includes clinical, electrophysiological and laboratory (CSF) criteria.", "Guillain-Barr syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF).", "Guillain-Barre syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF).", "Guillain-Barr\u00e9 syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF)." ], "type": "summary", "id": "627a9ff356bf9aee6f000025", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 335, "text": "Guillain-Barr\u00e9 syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF). Recently, the heterogeneity of GBS has been noticed with definition of several GBS variants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16206698", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 881, "text": "The diagnosis of GBS has been established in 17 patients according to clinical, electrophysiological and laboratory (CSF) criteria.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16206698", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Guillain-Barre syndrome (GBS) is a life-threatening immune-mediated acute inflammatory polyneuropathy and is associated with various antecedent infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32192609", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Guillain-Barr\u00e9 syndrome (GBS) is a potentially life-threatening immune-mediated acute inflammatory polyneuropathy associated with several antecedent infections. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30895887", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Acute Guillain-Barre syndrome (GBS) is a demyelinating polyneuropathy which responds readily to plasma exchange (PEX). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9365863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Guillain-Barre syndrome (GBS) is an acquired disease of the peripheral nervous system which causes demyelination and leads to weakness, ataxia, and areflexia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23431480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Guillain-Barr\u00e9 syndrome (GBS) is an acute inflammatory polyradiculoneuropathy, which has various clinical presentations and both axonal and demyelinating forms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23117942", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Guillain-Barr\u00e9 syndrome (GBS) is an autoimmune disease that leads to an axonal demyelination and/or degeneration of peripheral nerves through molecular mimicry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15921641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "Guillain-Barre syndrome (GBS) is a heterogenous group of peripheral-nerve disorders with similar clinical presentation characterized by acute, self-limited, progressive, bilateral and relatively symmetric ascending flaccid paralysis, which peaks in 2-4 weeks and then subsides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24872655", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Guillain-Barre syndrome (GBS) is an autoimmune polyradiculoneuropathy usually preceded by respiratory tract or gastrointestinal infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30069105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Guillain-Barre syndrome (GBS) is an acute immune-mediated progressive predominantly motor symmetric polyradiculoneuropathy which causes demyelination and leads to weakness, ataxia and areflexia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34434441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Guillain-Barre Syndrome is a well described acute demyelinating polyradiculoneuropathy with a likely autoimmune basis characterized by progressive ascending muscle paralysis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26793497", "endSection": "abstract" } ] }, { "body": "Is lumbar puncture the first test that should be performed on a patient with increased intracranial pressure?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25685562", "http://www.ncbi.nlm.nih.gov/pubmed/21129599", "http://www.ncbi.nlm.nih.gov/pubmed/10608260", "http://www.ncbi.nlm.nih.gov/pubmed/2277190", "http://www.ncbi.nlm.nih.gov/pubmed/21541088", "http://www.ncbi.nlm.nih.gov/pubmed/11985377", "http://www.ncbi.nlm.nih.gov/pubmed/3550721", "http://www.ncbi.nlm.nih.gov/pubmed/5763958", "http://www.ncbi.nlm.nih.gov/pubmed/28965126", "http://www.ncbi.nlm.nih.gov/pubmed/3520526" ], "ideal_answer": [ "No. A lumbar puncture is contraindicated in any patient with signs of increased intracranial pressure because it may precipitate cerebral herniation and death. For this reason, a computed tomography (CT) or magnetic resonance imaging (MRI) scan is done first. When the findings of the scan are normal, a lumbar puncture can be performed, if needed.", "Lumbar puncture (LP) is usually contra-indicated in situations where the ICP is suspected to be high." ], "exact_answer": "no", "type": "yesno", "id": "627a6ef856bf9aee6f000020", "snippets": [ { "offsetInBeginSection": 158, "offsetInEndSection": 462, "text": "As an emergency diagnostic procedure, spinal puncture is indicated when CNS infection is suspected or to establish the diagnosis of subarachnoid hemorrhage when results of cranial computed tomography are normal. The major contraindication is elevated intracranial pressure with evidence of a mass lesion.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3520526", "endSection": "abstract" }, { "offsetInBeginSection": 583, "offsetInEndSection": 849, "text": "Brain shift is a contraindication to LP, whether CSF pressure is raised or not, and whether papilloedema is present or not. Subsequently, recommendations are offered for indications to perform CT before LP, grouped according to the safety and clinical utility of LP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11985377", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 210, "text": "Death following lumbar puncture (LP) is feared by physicians. Many opinions are found in literature on the question whether computed cranial tomography (CT) should be performed before LP, to prevent herniation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11985377", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 625, "text": "Headache, caused by cerebrospinal fluid (CSF) hypotension, is a frequent complication of lumbar puncture; hematic patch is a therapeutic option for severe cases. The most serious complication is cerebral herniation and, for its prevention, computed tomography (CT) or cerebral magnetic resonance imaging (MRI) must always be performed before lumbar puncture: a lesion with evident mass effect is a contraindication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21129599", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 339, "text": "Lumbar puncture (LP) is usually contra-indicated in situations where the ICP is suspected to be high.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10608260", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 436, "text": "Low-dose cranial computed tomography (LD-CCT) based on iterative reconstruction has been shown to have sufficient image quality to assess cerebrospinal fluid spaces (CSF) and midline structures but not to exclude subtle parenchymal pathologies. Patients without focal neurological deficits often undergo CCT before lumbar puncture (LP) to exclude contraindications to LP including brain herniation or increased CSF pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28965126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Lumbar puncture is performed routinely for diagnostic and therapeutic purposes in idiopathic intracranial hypertension, despite lumbar puncture being classically contraindicated in the setting of raised intracranial pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685562", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 410, "text": "Although generally considered innocuous, there may be considerable danger when lumbar puncture is performed in the presence of increased intracranial pressure, especially when a mass lesion is present.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3550721", "endSection": "abstract" }, { "offsetInBeginSection": 1360, "offsetInEndSection": 1619, "text": "Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2277190", "endSection": "abstract" }, { "offsetInBeginSection": 1604, "offsetInEndSection": 1789, "text": "There are few abnormal CT scans presenting a contraindication for lumbar puncture and the majority of these patients usually have clinical signs to suggest raised intracranial pressure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21541088", "endSection": "abstract" } ] }, { "body": "What laboratory abnormalities are commonly seen in patients with COVID-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33973190", "http://www.ncbi.nlm.nih.gov/pubmed/33726761", "http://www.ncbi.nlm.nih.gov/pubmed/32542934", "http://www.ncbi.nlm.nih.gov/pubmed/33936225", "http://www.ncbi.nlm.nih.gov/pubmed/32336069", "http://www.ncbi.nlm.nih.gov/pubmed/34374346", "http://www.ncbi.nlm.nih.gov/pubmed/32501877", "http://www.ncbi.nlm.nih.gov/pubmed/32344313", "http://www.ncbi.nlm.nih.gov/pubmed/32656888", "http://www.ncbi.nlm.nih.gov/pubmed/33548996", "http://www.ncbi.nlm.nih.gov/pubmed/33210948", "http://www.ncbi.nlm.nih.gov/pubmed/33986318", "http://www.ncbi.nlm.nih.gov/pubmed/32877961", "http://www.ncbi.nlm.nih.gov/pubmed/34258956", "http://www.ncbi.nlm.nih.gov/pubmed/33522493", "http://www.ncbi.nlm.nih.gov/pubmed/32352401", "http://www.ncbi.nlm.nih.gov/pubmed/34383402", "http://www.ncbi.nlm.nih.gov/pubmed/32449374", "http://www.ncbi.nlm.nih.gov/pubmed/32721958", "http://www.ncbi.nlm.nih.gov/pubmed/33482780", "http://www.ncbi.nlm.nih.gov/pubmed/33407543" ], "ideal_answer": [ "Common laboratory abnormalities among patients with COVID-19 include:\n\n1. Elevated inflammatory markers (e.g., ferritin, C-reactive protein, and erythrocyte sedimentation rate).\n2. Elevated aminotransaminase levels (i.e., AST, ALT).\n3. Elevated lactate dehydrogenase (LDH) levels.\n4. Lymphopenia, leucocytosis.\n\nAbnormalities in coagulation testing (e.g., increased D-Dimers, decreased platelets), elevated procalcitonin levels, and elevated troponin levels have also been reported. The degree of these abnormalities tends to correlate with disease severity." ], "exact_answer": [ [ "Elevated ferritin", "Increased serum ferritin" ], [ "Elevated CRP", "Elevated C-reactive protein", "High C-reactive protein", "Elevated high sensitivity C-reactive protein (hs-CRP)" ], [ "Elevated ESR", "Increased ESR", "High erythrocyte sedimentation rate (ESR)" ], [ "Leucocytosis", "Increased white blood cells (WBC)", "Increased polymorphonuclear leukocytes (PMN)" ], [ "Lymphopenia", "Decreased lymphocyte count" ], [ "Elevated aminotransferases", "Increased alanine aminotransferase (ALT)", "Increased aspartate aminotransferase (AST)", "Increased ALT", "Increased AST" ], [ "Elevated lactate dehydrogenase (LDH)", "Elevated lactic dehydrogenase (LDH)", "Increased LDH" ], [ "Elevated D-dimers", "Elevated levels of D-dimer", "Increased D-Dimer" ], [ "Increased troponin", "Elevated troponin", "Elevated hypersensitive cardiac troponin I (hs-CTnI)" ], [ "Hyponatremia" ], [ "Decreased platelet count", "Decreased platelets" ], [ "Decreased albumin" ], [ "Increased procalcitonin (PCT)", "Elevated procalcitonin" ], [ "Increased total bilirubin", "Increased bilirubin" ], [ "Increased creatinine" ] ], "type": "list", "id": "627a70e656bf9aee6f000021", "snippets": [ { "offsetInBeginSection": 819, "offsetInEndSection": 999, "text": "Increased serum ferritin (74.2%), high C-reactive protein (73.3%), and high erythrocyte sedimentation rate (ESR) (72.2%) were the most frequently reported laboratory abnormalities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33548996", "endSection": "abstract" }, { "offsetInBeginSection": 1674, "offsetInEndSection": 1983, "text": "Some specific laboratory indicators implied the deterioration of disease, such as leucocytosis, lymphopenia, platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, creatinine, creatine kinase (CK), lactic dehydrogenase (LDH), C-reactive protein, procalcitonin (PCT), and D-dimer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33548996", "endSection": "abstract" }, { "offsetInBeginSection": 2130, "offsetInEndSection": 2422, "text": "Most COVID-19 patients have fever and cough with lymphopenia and increased inflammatory indices, and the main CT feature is GGO involved bilateral lung. Patients with comorbidities and worse clinical symptoms, laboratory characteristics, and CT findings tend to have poor disease progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33548996", "endSection": "abstract" }, { "offsetInBeginSection": 757, "offsetInEndSection": 1022, "text": "Multivariate logistic regression analysis showed that lymphopenia, elevated level of d-dimer, hypersensitive cardiac troponin I (hs-CTnI) and high sensitivity C-reactive protein (hs-CRP) were independent predictors of mortality in young adults with severe COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33407543", "endSection": "abstract" }, { "offsetInBeginSection": 1272, "offsetInEndSection": 1396, "text": "Lymphopenia, elevated level of d-dimer, hs-CTnI and hs-CRP predicted clinical outcomes of young adults with severe COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33407543", "endSection": "abstract" }, { "offsetInBeginSection": 726, "offsetInEndSection": 1165, "text": "Compared to patients with a non-severe form of COVID-19, patients who had a severe form of disease revealed higher values for white blood cells (WBC), polymorphonuclear leukocytes (PMN), total bilirubin, alanine aminotransferase (ALT), creatinine, troponin, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. By contrast, platelet count, lymphocyte count, and albumin levels were decreased in patients with a severe form of COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33973190", "endSection": "abstract" }, { "offsetInBeginSection": 1277, "offsetInEndSection": 1516, "text": "Hyponatremia (50%), elevated C-reactive protein (CRP; 100%), and lactate dehydrogenase (LDH; 80%) were common. Acute renal failure, myocardial injury, and elevation in aminotransferases occurred in 69%, 19%, and 38% patients, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32352401", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 529, "text": "The most common laboratory abnormalities in COVID\u201119 include decreased lymphocyte count (35%-82.1%), thrombocytopenia (17%-36.2%), elevated serum C\u2011reactive protein (60.7%-93%), lactate dehydrogenase (41%-76%), and D\u2011dimer concentrations (36%-46.4%).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32336069", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 524, "text": "Thrombocytopenia, coagulation abnormalities, and disseminated intravascular coagulation were observed in COVID-19 patients, especially those with critical illness and non-survivors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32721958", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 732, "text": "In conclusion, abnormalities in aminotransferase, lactate dehydrogenase, and ferritin levels are commonly seen in COVID-19 related liver injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32501877", "endSection": "abstract" }, { "offsetInBeginSection": 932, "offsetInEndSection": 1220, "text": "In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32344313", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 219, "text": "Clinical observations demonstrated that COVID-19 related pneumonia is often accompanied by hematological and coagulation abnormalities including lymphopenia, thrombocytopenia, and prolonged prothrombin time.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33210948", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1517, "text": "Lymphopenia is the mostly commonly reported laboratory abnormality and occurs in over 50% of COVID-19 patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32542934", "endSection": "abstract" }, { "offsetInBeginSection": 1341, "offsetInEndSection": 1575, "text": "Laboratory findings are unspecific in COVID-19 patients; laboratory abnormalities include lymphopenia, elevated of LDH, CPK and the inflammatory markers, such as C reactive protein, ferritinemia and the erythrocyte sedimentation rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33522493", "endSection": "abstract" }, { "offsetInBeginSection": 966, "offsetInEndSection": 1092, "text": "The common laboratory features reported include lymphopenia, elevated levels of C-reactive proteins and lactate dehydrogenase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33482780", "endSection": "abstract" } ] }, { "body": "Do only changes in coding regions of MEF2C cause developmental disorders?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34022131" ], "ideal_answer": [ "No. Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms." ], "exact_answer": "no", "type": "yesno", "id": "61f80d5d882a024a1000003c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34022131", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1608, "text": "Clinical genetic testing of protein-coding regions identifies a likely causative variant in only around half of developmental disorder (DD) cases. The contribution of regulatory variation in non-coding regions to rare disease, including DD, remains very poorly understood. We screened 9,858 probands from the Deciphering Developmental Disorders (DDD) study for de novo mutations in the 5' untranslated regions (5' UTRs) of genes within which variants have previously been shown to cause DD through a dominant haploinsufficient mechanism. We identified four single-nucleotide variants and two copy-number variants upstream of MEF2C in a total of ten individual probands. We developed multiple bespoke and orthogonal experimental approaches to demonstrate that these variants cause DD through three distinct loss-of-function mechanisms, disrupting transcription, translation, and/or protein function. These non-coding region variants represent 23% of likely diagnoses identified in MEF2C in the DDD cohort, but these would all be missed in standard clinical genetics approaches. Nonetheless, these variants are readily detectable in exome sequence data, with 30.7% of 5' UTR bases across all genes well covered in the DDD dataset. Our analyses show that non-coding variants upstream of genes within which coding variants are known to cause DD are an important cause of severe disease and demonstrate that analyzing 5' UTRs can increase diagnostic yield. We also show how non-coding variants can help inform both the disease-causing mechanism underlying protein-coding variants and dosage tolerance of the gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34022131", "endSection": "abstract" } ] }, { "body": "Which factor is inhibited by Milvexian?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34558200", "http://www.ncbi.nlm.nih.gov/pubmed/34752670", "http://www.ncbi.nlm.nih.gov/pubmed/34494428", "http://www.ncbi.nlm.nih.gov/pubmed/34780683" ], "ideal_answer": [ "Milvexian is a small molecule, active-site inhibitor of factor XIa (FXIa) being developed to prevent and treat thrombotic events." ], "exact_answer": [ "XIa" ], "type": "factoid", "id": "61f58de2882a024a1000000a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34494428", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "First-in-human study of milvexian, an oral, direct, small molecule factor XIa inhibitor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34558200", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Milvexian (BMS-986177/JNJ-70033093) is a small molecule, active-site inhibitor of factor XIa (FXIa) being developed to prevent and treat thrombotic events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34558200", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 294, "text": "Additional data are needed regarding the efficacy and safety of milvexian, an oral factor XIa inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780683", "endSection": "abstract" }, { "offsetInBeginSection": 1817, "offsetInEndSection": 2033, "text": "CONCLUSIONS: Postoperative factor XIa inhibition with oral milvexian in patients undergoing knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780683", "endSection": "abstract" }, { "offsetInBeginSection": 1823, "offsetInEndSection": 2039, "text": "SIONS: Postoperative factor XIa inhibition with oral milvexian in patients undergoing knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Fund", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "BACKGROUND: Milvexian (BMS-986177/JNJ-70033093) is an orally bioavailable factor XIa (FXIa) inhibitor currently in phase 2\u00a0clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34752670", "endSection": "abstract" }, { "offsetInBeginSection": 465, "offsetInEndSection": 607, "text": "S: Milvexian is an active-site, reversible inhibitor of human and rabbit FXIa (Ki 0.11 and 0.38\u00a0nM, respectively). Milvexian increased activat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34752670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Milvexian, an orally bioavailable, small-molecule, reversible, direct inhibitor of factor XIa: In vitro studies and in vivo evaluation in experimental thrombosis in rabbits.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34752670", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Milvexian (BMS-986177/JNJ-70033093) is a small molecule, active-site inhibitor of factor XIa (FXIa) being developed to prevent and treat thrombotic events. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34558200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "BACKGROUND: Milvexian (BMS-986177/JNJ-70033093) is an orally bioavailable factor XIa (FXIa) inhibitor currently in phase 2\u00a0clinica", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34752670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Milvexian (BMS-986177/JNJ-70033093) is a small molecule, active-site inhibitor of factor XIa (FXIa) being developed to prevent and treat thrombotic events.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34558200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 537, "text": "BACKGROUND: Milvexian (BMS-986177/JNJ-70033093) is an orally bioavailable factor XIa (FXIa) inhibitor currently in phase 2\u00a0clinical trials.OBJECTIVES: To evaluate in vitro properties and in vivo characteristics of milvexian.METHODS: In vitro properties of milvexian were evaluated with coagulation and enzyme assays, and in vivo profiles were characterized with rabbit models of electrolytic-induced carotid arterial thrombosis and cuticle bleeding time (BT).RESULTS: Milvexian is an active-site, reversible inhibitor of human and rabbit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34752670", "endSection": "abstract" }, { "offsetInBeginSection": 178, "offsetInEndSection": 562, "text": "coagulants. Additional data are needed regarding the efficacy and safety of milvexian, an oral factor XIa inhibitor.METHODS: In this parallel-group, phase 2 trial, we randomly assigned 1242 patients undergoing knee arthroplasty to receive one of seven postoperative regimens of milvexian (25 mg, 50 mg, 100 mg, or 200 mg twice daily or 25 mg, 50 mg, or 200 mg once daily) or enoxapari", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780683", "endSection": "abstract" }, { "offsetInBeginSection": 1685, "offsetInEndSection": 1808, "text": "emostasis, even when combined with aspirin in rabbits. This study supports inhibition of FXIa with milvexian as a promising", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34752670", "endSection": "abstract" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1990, "text": "k of 30% (one-sided P<0.001). Bleeding of any severity occurred in 38 of 923 patients (4%) taking milvexian and in 12 of 296 patients (4%) taking enoxaparin; major or clinically relevant nonmajor bleeding occurred in 1% and 2%, respectively; and serious adverse events were reported in 2% and 4%, respectively.CONCLUSIONS: Postoperative factor XIa inhibition with oral milvexian in patients undergoing knee arthroplasty was effective for the prevention of venous thromboembolism and ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34780683", "endSection": "abstract" } ] }, { "body": "What is Granzyme B?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32324629", "http://www.ncbi.nlm.nih.gov/pubmed/32302642", "http://www.ncbi.nlm.nih.gov/pubmed/32079690", "http://www.ncbi.nlm.nih.gov/pubmed/34549432", "http://www.ncbi.nlm.nih.gov/pubmed/32608278", "http://www.ncbi.nlm.nih.gov/pubmed/34509050" ], "ideal_answer": [ "Granzyme B is a serine protease that is secreted by Natural Killer (NK) cells and cytotoxic T lymphocytes during a cellular immune response and can induce apoptosis." ], "exact_answer": [ "Granzyme B is a serine protease" ], "type": "factoid", "id": "6217d9de3a8413c653000025", "snippets": [ { "offsetInBeginSection": 1122, "offsetInEndSection": 1192, "text": "expression of the non-specific cytotoxic cell marker (granzyme B, grb)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34549432", "endSection": "abstract" }, { "offsetInBeginSection": 483, "offsetInEndSection": 542, "text": " cytotoxic protein-positive cells, such as granzyme B cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32324629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Granzyme B is known to be a serine protease contained in granules of cytotoxic T cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32302642", "endSection": "abstract" }, { "offsetInBeginSection": 473, "offsetInEndSection": 532, "text": "including cytotoxic T cells (CD8, Granzyme B, OX40, Ki67),\n", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32079690", "endSection": "abstract" }, { "offsetInBeginSection": 195, "offsetInEndSection": 361, "text": "Granzyme B is a serine protease that is secreted by Natural Killer (NK) cells and cytotoxic T lymphocytes during a cellular immune response and can induce apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32608278", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 507, "text": "markers of activated cytotoxic T lymphocytes (CD8, granzyme-B) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34509050", "endSection": "abstract" } ] }, { "body": "Is CircRNA produced by back splicing of exon, intron or both, forming exon or intron circRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32751504", "http://www.ncbi.nlm.nih.gov/pubmed/28265491", "http://www.ncbi.nlm.nih.gov/pubmed/33614648", "http://www.ncbi.nlm.nih.gov/pubmed/31931031", "http://www.ncbi.nlm.nih.gov/pubmed/33662561", "http://www.ncbi.nlm.nih.gov/pubmed/27365365", "http://www.ncbi.nlm.nih.gov/pubmed/34160816", "http://www.ncbi.nlm.nih.gov/pubmed/34313732", "http://www.ncbi.nlm.nih.gov/pubmed/34179306", "http://www.ncbi.nlm.nih.gov/pubmed/29322444", "http://www.ncbi.nlm.nih.gov/pubmed/29116363", "http://www.ncbi.nlm.nih.gov/pubmed/33649838" ], "ideal_answer": [ "Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA." ], "exact_answer": "yes", "type": "yesno", "id": "62211c853a8413c65300006d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "CircRNAs are a subclass of lncRNAs that have been found to be abundantly present in a wide range of species, including humans. CircRNAs are generally produced by a noncanonical splicing event called backsplicing that is dependent on the canonical splicing machinery, giving rise to circRNAs classified into three main categories: exonic circRNA, circular intronic RNA, and exon-intron circular RNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34160816", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Circular RNA (circRNA) is a large class of covalently closed circRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34313732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322444", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 906, "text": "Analyses of the other reads revealed two origins for non-canonical circRNAs: (1) Intronic sequences for lariat-derived intronic circRNAs and intron circles, (2) Mono-exonic genes (mostly non-coding) for either a new type of circRNA (including only part of the exon: sub-exonic circRNAs) or, even more rarely, mono-exonic canonical circRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32751504", "endSection": "abstract" }, { "offsetInBeginSection": 117, "offsetInEndSection": 258, "text": "Our objective was to characterize non-canonical circRNAs, namely not originating from back splicing and circRNA produced by non-coding genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32751504", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 332, "text": "Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31931031", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 352, "text": "CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34313732", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28265491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Exonic circular RNAs (circRNAs) are RNA molecules that are covalently closed by back-splicing via canonical splicing machinery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33662561", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29322444", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Circular RNAs (circRNAs) are a class of non\u2011coding RNAs formed by covalently closed loops through back\u2011splicing and exon\u2011skipping. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33649838", "endSection": "abstract" }, { "offsetInBeginSection": 405, "offsetInEndSection": 751, "text": "Here, we review the emerging understanding that both, circRNAs produced by co- and posttranscriptional head-to-tail \"backsplicing\" of a downstream splice donor to a more upstream splice acceptor, as well as circRNAs generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions in eukaryotes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29116363", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 943, "text": "Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3' poly-(A) tail or 5' cap, rendering them immune to exonuclease-mediated degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33614648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "CircRNAs are a large class of endogenous single-stranded RNA that is different from other linear RNA, which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34179306", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27365365", "endSection": "abstract" } ] }, { "body": "How does condensin affect the function of topoisomeraseII?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24062159", "http://www.ncbi.nlm.nih.gov/pubmed/22236810", "http://www.ncbi.nlm.nih.gov/pubmed/17360754", "http://www.ncbi.nlm.nih.gov/pubmed/14600262", "http://www.ncbi.nlm.nih.gov/pubmed/23133392" ], "ideal_answer": [ "Condensin prevents deleterious anaphase bridges during chromosome segregation by promoting sister chromatid decatenation.", "aids sister chromatid decatenation by topoisomerase II", "Condensin prevents deleterious anaphase bridges during chromosome segregation by promoting sister chromatid decatenation which are created by topoisomerase II. Condensin-dependent localisation of topoisomerase II to an axial chromosomal structure is required for sister chromatid resolution during mitosis.", "aids sister chromatid decatenation", "Condensin interferes with the function of Topo II. It prevents catenanes from persisting between sister chromatids during mitosis.", "Condensin aids sister chromatid decatenation by topoisomerase II and minimizes topoisomerase II-mediated entanglements of DNA in vivo" ], "type": "summary", "id": "5fe31323a43ad3127800004d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Condensin aids sister chromatid decatenation by topoisomerase II.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24062159", "endSection": "title" }, { "offsetInBeginSection": 216, "offsetInEndSection": 467, "text": "Anaphase bridges observed in cells lacking condensin are reminiscent of chromosome segregation failure after inactivation of topoisomerase II (topo II), the enzyme that removes catenanes persisting between sister chromatids following DNA replication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24062159", "endSection": "abstract" }, { "offsetInBeginSection": 1026, "offsetInEndSection": 1162, "text": "Complete resolution, however, requires the condensin complex, a dependency that becomes more pronounced with increasing chromosome size.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24062159", "endSection": "abstract" }, { "offsetInBeginSection": 1197, "offsetInEndSection": 1318, "text": "condensin prevents deleterious anaphase bridges during chromosome segregation by promoting sister chromatid decatenation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24062159", "endSection": "abstract" }, { "offsetInBeginSection": 578, "offsetInEndSection": 772, "text": "We propose a model of how metaphase chromosomes could be shaped based on the enzymatic activities of condensin and topoisomerase II in overwinding and relaxation of the DNA fiber during mitosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22236810", "endSection": "abstract" }, { "offsetInBeginSection": 790, "offsetInEndSection": 1012, "text": "ondensin overwinding is an important requirement for intertwine resolution by topoisomerase II and, together with the inhibition of transcription, contributes to cytological mitotic chromosome appearance or 'condensation'.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22236810", "endSection": "abstract" }, { "offsetInBeginSection": 1241, "offsetInEndSection": 1422, "text": "We also found spindle force, anaphase, or cytokinesis to be dispensable. RSZ breakage, however, required genes encoding condensin subunits (YCG1, YSC4) and topoisomerase II (TOP2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23133392", "endSection": "abstract" }, { "offsetInBeginSection": 867, "offsetInEndSection": 1040, "text": "BGLF4 also stimulates the decatenation activity of topoisomerase II, suggesting that it may induce chromosome condensation through condensin and topoisomerase II activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17360754", "endSection": "abstract" }, { "offsetInBeginSection": 708, "offsetInEndSection": 866, "text": "BGLF4 interacts with condensin complexes, the major components in mitotic chromosome assembly, and induces condensin phosphorylation at Cdc2 consensus motifs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17360754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Condensin-dependent localisation of topoisomerase II to an axial chromosomal structure is required for sister chromatid resolution during mitosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14600262", "endSection": "title" }, { "offsetInBeginSection": 1533, "offsetInEndSection": 1684, "text": "condensin is required so that an axial chromatid structure can be organised where topoisomerase II can effectively promote sister chromatid resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14600262", "endSection": "abstract" } ] }, { "body": "Which signaling pathway does LY294002 inhibit?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34820336" ], "ideal_answer": [ "LY294002, can block the PI3K/AKT signaling pathway." ], "exact_answer": [ "PI3K/AKT" ], "type": "factoid", "id": "6206c22ac9dfcb9c0900003e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "LY294002 Is a Promising Inhibitor to Overcome Sorafenib Resistance in FLT3-ITD Mutant AML Cells by Interfering With PI3K/Akt Signaling Pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34820336", "endSection": "title" }, { "offsetInBeginSection": 1507, "offsetInEndSection": 1652, "text": "PI3K inhibitor, LY294002, can block PI3K/AKT signaling, further inhibit glycolysis to disturb ATP production, and finally induce cell apoptosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34820336", "endSection": "abstract" } ] }, { "body": "Is METTL1 overexpression associated with better patient survival?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34352207" ], "ideal_answer": [ "No. METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival." ], "exact_answer": "no", "type": "yesno", "id": "620c27e93a8413c653000006", "snippets": [ { "offsetInBeginSection": 227, "offsetInEndSection": 547, "text": " Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m7G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34352207", "endSection": "abstract" } ] }, { "body": "List monoclonal antibodies included in the REGEN-COV.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34393218", "http://www.ncbi.nlm.nih.gov/pubmed/34159344", "http://www.ncbi.nlm.nih.gov/pubmed/34159343", "http://www.ncbi.nlm.nih.gov/pubmed/34587383", "http://www.ncbi.nlm.nih.gov/pubmed/34716907", "http://www.ncbi.nlm.nih.gov/pubmed/34347950", "http://www.ncbi.nlm.nih.gov/pubmed/34673689", "http://www.ncbi.nlm.nih.gov/pubmed/34463470" ], "ideal_answer": [ "REGEN-COV is a combination of the monoclonal antibodies casirivimab and imdevimab. It has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019." ], "exact_answer": [ [ "casirivimab" ], [ "imdevimab" ] ], "type": "list", "id": "61f58ef3882a024a1000000b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "REGEN-COV is a cocktail of two human IgG1 monoclonal antibodies (REGN10933 + REGN10987) that targets severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and has shown great promise to reduce the SARS-CoV-2 viral load in COVID-19 patients enrolled in clinical studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34463470", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Background: Casirivimab and imdevimab (REGEN-COV\u2122) markedly reduces risk of hospitalization or death in high-risk individuals with Covid-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34159344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "BACKGROUND: REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34347950", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 748, "text": "In the US, the FDA has given Emergency Use Authorization (EUA) for two neutralizing therapeutic monoclonal antibody 'cocktails,' casirivimab and imdevimab (REGEN-COV), bamlanivimab and etesevimab, and one monotherapy, bamlanivimab, for prophylactic post-exposure therapy in individuals at high risk of progressing to severe COVID-19. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34393218", "endSection": "abstract" }, { "offsetInBeginSection": 414, "offsetInEndSection": 747, "text": "In the US, the FDA has given Emergency Use Authorization (EUA) for two neutralizing therapeutic monoclonal antibody 'cocktails,' casirivimab and imdevimab (REGEN-COV), bamlanivimab and etesevimab, and one monotherapy, bamlanivimab, for prophylactic post-exposure therapy in individuals at high risk of progressing to severe COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34393218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "The emergency use authorization for REGEN-COV (a combination of two monoclonal antibodies, casirivimab and imdevimab) has been revised to include postexposure prophylaxis of COVID-19 in adults and children 12 years of age and older who, if they become COVID-19 positive, are at high risk for severe disease.Prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34673689", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "BACKGROUND: REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34347950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587383", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 768, "text": " the FDA has given Emergency Use Authorization (EUA) for two neutralizing therapeutic monoclonal antibody 'cocktails,' casirivimab and imdevimab (REGEN-COV), bamlanivimab and etesevimab, and one monotherapy, bamlanivimab, for prophylactic post-exposure therapy in individuals at high risk of progressing to severe COVID-19. Preclinical and clin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34393218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587383", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 249, "text": "BACKGROUND: REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34347950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Casirivimab/imdevimab (Ronapreve\u2122; REGEN-COV\u2122) is a co-packaged combination of two neutralizing immunoglobulin gamma 1 (IgG1) human monoclonal antibodies (casirivimab and imdevimab) against the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34716907", "endSection": "abstract" } ] }, { "body": "Which disease is caused by mutations in the gene PRF1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34339548", "http://www.ncbi.nlm.nih.gov/pubmed/29216683", "http://www.ncbi.nlm.nih.gov/pubmed/33869605", "http://www.ncbi.nlm.nih.gov/pubmed/31865540" ], "ideal_answer": [ "The presence of mutations in PRF1, UNC13D, STX11 and STXBP2 genes in homozygosis or compound heterozygosis results in immune deregulation. Most such cases lead to clinical manifestations of haemophagocytic lymphohistiocytosis (HLH)." ], "exact_answer": [ "haemophagocytic lymphohistiocytosis (HLH)" ], "type": "factoid", "id": "6217db1b3a8413c653000027", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34339548", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "The presence of mutations in PRF1, UNC13D, STX11 and STXBP2 genes in homozygosis or compound heterozygosis results in immune deregulation. Most such cases lead to clinical manifestations of haemophagocytic lymphohistiocytosis (HLH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31865540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Adult onset type 2 familial hemophagocytic lymphohistiocytosis with PRF1 c.65delC/c.163C>T compound heterozygous mutations: A case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33869605", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 138, "text": "Deleterious mutations in PRF1 result in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29216683", "endSection": "abstract" } ] }, { "body": "What protein is encoded by the GRN gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31962288", "http://www.ncbi.nlm.nih.gov/pubmed/22277331", "http://www.ncbi.nlm.nih.gov/pubmed/30862089", "http://www.ncbi.nlm.nih.gov/pubmed/31626287", "http://www.ncbi.nlm.nih.gov/pubmed/33433878", "http://www.ncbi.nlm.nih.gov/pubmed/33028409", "http://www.ncbi.nlm.nih.gov/pubmed/33433870", "http://www.ncbi.nlm.nih.gov/pubmed/32507413", "http://www.ncbi.nlm.nih.gov/pubmed/34433069", "http://www.ncbi.nlm.nih.gov/pubmed/32929860", "http://www.ncbi.nlm.nih.gov/pubmed/31864418", "http://www.ncbi.nlm.nih.gov/pubmed/26652843", "http://www.ncbi.nlm.nih.gov/pubmed/31291241", "http://www.ncbi.nlm.nih.gov/pubmed/29744576", "http://www.ncbi.nlm.nih.gov/pubmed/33636385", "http://www.ncbi.nlm.nih.gov/pubmed/24503614", "http://www.ncbi.nlm.nih.gov/pubmed/24709683", "http://www.ncbi.nlm.nih.gov/pubmed/28828399", "http://www.ncbi.nlm.nih.gov/pubmed/28778989", "http://www.ncbi.nlm.nih.gov/pubmed/20946666", "http://www.ncbi.nlm.nih.gov/pubmed/23383391", "http://www.ncbi.nlm.nih.gov/pubmed/29053785" ], "ideal_answer": [ "Loss-of-function mutations in the gene encoding for the protein progranulin (PGRN), GRN, are one of the major genetic abnormalities involved in frontotemporal lobar degeneration." ], "exact_answer": [ "progranulin" ], "type": "factoid", "id": "62211f453a8413c653000072", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Loss-of-function mutations in the gene encoding for the protein progranulin (PGRN), GRN, are one of the major genetic abnormalities involved in frontotemporal lobar degeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32507413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Numerous kindreds with familial frontotemporal lobar degeneration have been linked to mutations in microtubule-associated protein tau (MAPT) or progranulin (GRN) genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "BACKGROUND: Progranulin protein (PGRN) is a cysteine-rich growth factor encoded by the progranulin gene (GRN).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24503614", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 358, "text": "Due to the highly diverse biological functions of the progranulin (PGRN) protein, encoded by GRN, multiple possible disease mechanisms have been proposed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Single nucleotide polymorphisms (SNPs) in TMEM106B encoding the lysosomal type II transmembrane protein 106B increase the risk for frontotemporal lobar degeneration (FTLD) of GRN (progranulin gene) mutation carriers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32929860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "BACKGROUND: Progranulin protein (PGRN) is a cysteine-rich growth factor encoded by the progranulin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24503614", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "GRN, the gene coding for the progranulin (PGRN) protein, was recognized as a gene linked to frontotemporal lobar degeneration (FTLD). Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26652843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Progranulin (PGRN) is a protein encoded by the GRN gene with multiple identified functions including as a neurotrophic factor, tumorigenic growth factor, anti-inflammatory cytokine and regulator of lysosomal function. A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31864418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Mutations in the GRN gene coding for progranulin (PGRN) are responsible for many cases of familial frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein 43 (TDP-43)-positive inclusions (FTLD-TDP). GRN", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31626287", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 328, "text": "ozygous loss-of-function mutations in the gene encoding the progranulin protein (Granulin Precursor, GRN) are a common cause of familial frontotemporal dementia (FTD). Gene t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33636385", "endSection": "abstract" }, { "offsetInBeginSection": 449, "offsetInEndSection": 740, "text": "ne of these genes (GRN), which encodes progranulin, have been implicated in up to a quarter of cases of frontotemporal lobar degeneration with TDP-43 (TAR DNA-binding protein 43)-positive inclusions; currently, there are more than 60 known pathogenic mutations of the gene. We present the cl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24709683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 262, "text": "Mutation in the GRN gene, encoding the progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results in frontotemporal lobar degeneration (FTLD) and complete loss results in neuronal ceroid lipofuscinosis (NCL). Altho", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31291241", "endSection": "abstract" }, { "offsetInBeginSection": 480, "offsetInEndSection": 716, "text": "e on FTD caused by mutations in the GRN gene, which encodes a secreted protein, progranulin (PGRN), that has diverse roles in regulating cell survival, immune responses, and autophagy and lysosome function in the brain. FTD-linked mutat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31962288", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 365, "text": "to the highly diverse biological functions of the progranulin (PGRN) protein, encoded by GRN, multiple possible disease mechanisms have been proposed. Early ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33433878", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 439, "text": " most common pathological subtype, FTLD with transactive response DNA-binding protein with a molecular weight of 43 kDa inclusions (FTLD-TDP), is often caused by autosomal dominant mutations in the progranulin gene (GRN) encoding the progranulin protein (PGRN). GRN pa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22277331", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29053785", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Homozygous or heterozygous mutations in the GRN gene, encoding progranulin (PGRN), cause neuronal ceroid lipofuscinosis (NCL) or frontotemporal dementia (FTD), respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28828399", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 321, "text": "Heterozygous loss-of-function mutations in the gene encoding the progranulin protein (Granulin Precursor, GRN) are a common cause of familial frontotemporal dementia (FTD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33636385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 217, "text": "Progranulin (PGRN) is a protein encoded by the GRN gene with multiple identified functions including as a neurotrophic factor, tumorigenic growth factor, anti-inflammatory cytokine and regulator of lysosomal function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31864418", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: Progranulin (PGRN) encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiologica", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20946666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Progranulin (PGRN), encoded by the GRN gene in humans, is a secreted growth factor implicated in a multitude of processes ranging from regulation of inflammation to wound healing and tumorigenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29744576", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Mutation in the GRN gene, encoding the progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results in frontotemporal lobar degeneration (FTLD) and complete loss results in neuronal ceroid lipofuscinosis (NCL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31291241", "endSection": "abstract" }, { "offsetInBeginSection": 468, "offsetInEndSection": 699, "text": "We focus here on FTD caused by mutations in the GRN gene, which encodes a secreted protein, progranulin (PGRN), that has diverse roles in regulating cell survival, immune responses, and autophagy and lysosome function in the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31962288", "endSection": "abstract" }, { "offsetInBeginSection": 396, "offsetInEndSection": 602, "text": "By studying mice lacking progranulin (PGRN), the protein encoded by GRN, we discovered multiple lines of evidence that PGRN deficiency results in impairment of autophagy, a key cellular degradation pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28778989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Loss-of-function mutations in the progranulin gene (GRN), which encodes progranulin (PGRN), are a major cause of frontotemporal dementia (FTD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34433069", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 427, "text": "The recent discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD), and other neurodegenerative diseases leading to dementia, has brought renewed interest in progranulin and its functions in the central nervous system.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23383391", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Heterozygous, loss-of-function mutations in the granulin gene (GRN) encoding progranulin (PGRN) are a common cause of frontotemporal dementia (FTD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33028409", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 330, "text": " progranulin (PGRN). PGRN is a glycoprotein encoded by the GRN/Grn gene with multiple cellular functions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30862089", "endSection": "abstract" } ] }, { "body": "What is the difference in the roles of Tcf1 and Tcf3 during development?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21685894", "http://www.ncbi.nlm.nih.gov/pubmed/22573616", "http://www.ncbi.nlm.nih.gov/pubmed/24832538" ], "ideal_answer": [ "\u03a4here are opposing effects of Tcf3 and Tcf1 in the control of Wnt stimulation of embryonic stem cell self-renewal. In contrast to \u03b2-catenin-dependent functions described for Tcf1 the known embryonic functions for Tcf3 are consistent with \u03b2-catenin-independent repressor activity. Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling.", "Tcf3 antagonizes Wnt signaling, while Tcf1 enhances" ], "type": "summary", "id": "5fdb4176a43ad3127800001a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685894", "endSection": "title" }, { "offsetInBeginSection": 777, "offsetInEndSection": 1022, "text": "Interestingly, both Tcf3-\u03b2-catenin and Tcf1-\u03b2-catenin interactions contributed to Wnt stimulation of self-renewal and gene expression, and the combination of Tcf3 and Tcf1 recruited Wnt-stabilized \u03b2-catenin to Oct4 binding sites on ESC chromatin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21685894", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 344, "text": "In contrast to \u03b2-catenin-dependent functions described for Tcf1, Tcf4 and Lef1, the known embryonic functions for Tcf3 in mice, frogs and fish are consistent with \u03b2-catenin-independent repressor activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22573616", "endSection": "abstract" }, { "offsetInBeginSection": 1070, "offsetInEndSection": 1164, "text": "Tcf3 directly represses transcription of Lef1, which is stimulated by Wnt/\u03b2-catenin activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22573616", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Tcf3 represses Wnt-\u03b2-catenin signaling and maintains neural stem cell population during neocortical development", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24832538", "endSection": "title" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1287, "text": "We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling, in NPCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24832538", "endSection": "abstract" } ] }, { "body": "Why mix \u03b3-cyclodextrin with grapefruit juice?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31828807" ], "ideal_answer": [ "Grapefruit (Citrus paradisi) juice enhances the oral bioavailability of drugs that are metabolized by intestinal cytochrome P450 3A4 (CYP3A4). Patients are advised to avoid drinking grapefruit juice to prevent this drug-grapefruit juice interaction. The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with \u03b3CD. The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with \u03b3CD. Similar attenuation effects by \u03b3CD were observed in the cases of BG and DHBG. Furthermore, BG and DHBG were suggested to be strongly encapsulated in the cavity of \u03b3CD.The encapsulation of BG and DHBG by \u03b3CD and the resulting attenuation of the inhibition of CYP3A activity by grapefruit juice may be applicable to juice processing for preventing drug-grapefruit juice interactions." ], "type": "summary", "id": "62058382c9dfcb9c09000031", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 261, "text": "Grapefruit (Citrus paradisi) juice enhances the oral bioavailability of drugs that are metabolized by intestinal cytochrome P450 3A4 (CYP3A4). Patients are advised to avoid drinking grapefruit juice to prevent this drug-grapefruit juice interaction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31828807", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1389, "text": "The encapsulation of BG and DHBG by \u03b3CD and the resulting attenuation of the inhibition of CYP3A activity by grapefruit juice may be applicable to juice processing for preventing drug-grapefruit juice interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31828807", "endSection": "abstract" }, { "offsetInBeginSection": 886, "offsetInEndSection": 1163, "text": "The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with \u03b3CD. Similar attenuation effects by \u03b3CD were observed in the cases of BG and DHBG. Furthermore, BG and DHBG were suggested to be strongly encapsulated in the cavity of \u03b3CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31828807", "endSection": "abstract" } ] }, { "body": "What is disrupted by ALS- and FTD-associated missense mutations in TBK1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34099552" ], "ideal_answer": [ "ALS- and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy." ], "exact_answer": [ "mitophagy" ], "type": "factoid", "id": "62190ca03a8413c653000035", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "ALS- and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34099552", "endSection": "title" } ] }, { "body": "What is Morel\u2013Lavall\u00e9e lesion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22266744", "http://www.ncbi.nlm.nih.gov/pubmed/27579812", "http://www.ncbi.nlm.nih.gov/pubmed/33508615", "http://www.ncbi.nlm.nih.gov/pubmed/34401233", "http://www.ncbi.nlm.nih.gov/pubmed/33792213", "http://www.ncbi.nlm.nih.gov/pubmed/32716145", "http://www.ncbi.nlm.nih.gov/pubmed/24639319", "http://www.ncbi.nlm.nih.gov/pubmed/23332912", "http://www.ncbi.nlm.nih.gov/pubmed/30652431", "http://www.ncbi.nlm.nih.gov/pubmed/30025335", "http://www.ncbi.nlm.nih.gov/pubmed/33438963", "http://www.ncbi.nlm.nih.gov/pubmed/23739602", "http://www.ncbi.nlm.nih.gov/pubmed/30547132", "http://www.ncbi.nlm.nih.gov/pubmed/25114393", "http://www.ncbi.nlm.nih.gov/pubmed/25785224", "http://www.ncbi.nlm.nih.gov/pubmed/26506679", "http://www.ncbi.nlm.nih.gov/pubmed/26965645", "http://www.ncbi.nlm.nih.gov/pubmed/17351119", "http://www.ncbi.nlm.nih.gov/pubmed/33217297", "http://www.ncbi.nlm.nih.gov/pubmed/33310472", "http://www.ncbi.nlm.nih.gov/pubmed/20463988", "http://www.ncbi.nlm.nih.gov/pubmed/33936913", "http://www.ncbi.nlm.nih.gov/pubmed/33775030", "http://www.ncbi.nlm.nih.gov/pubmed/26023620", "http://www.ncbi.nlm.nih.gov/pubmed/24161364", "http://www.ncbi.nlm.nih.gov/pubmed/32335518", "http://www.ncbi.nlm.nih.gov/pubmed/32257483" ], "ideal_answer": [ "Morel-Lavall\u00e9e lesion is a closed degloving soft-tissue injury that results in the accumulation of a hemolymphatic fluid between the skin/superficial fascia and the deep fascia." ], "type": "summary", "id": "61f59012882a024a1000000c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "Morel-Lavall\u00e9e lesion is a post-traumatic degloving cyst, usually filled with blood, lymph or necrotic tissue, which mostly develops in the area around greater trochanter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33775030", "endSection": "abstract" }, { "offsetInBeginSection": 1295, "offsetInEndSection": 1594, "text": "CONCLUSIONS: Characteristic features of ML lesion include a fusiform fluid collection between the subcutaneous fat and the underlying fascia after shearing injury. Six types can be differentiated on MRI, with the seroma, the subacute hematoma and the chronic organizing hematoma being the commonest.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33792213", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Morel-Lavall\u00e9e lesion (MLL) is a closed degloving soft-tissue injury that results in the accumulation of a hemolymphatic fluid between the skin/superficial fascia and the deep fascia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33936913", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "The Morel-Lavall\u00e9e lesion is a closed internal soft-tissue degloving injury. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34401233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "INTRODUCTION: A Morel-Lavall\u00e9e lesion (MLL) is a rare and aesthetically concerning condition caused by a shearing force between subcutaneous fat and underlying fascia. Subsequent seroma formation occurs after the initial trauma of a crush injury, ligamentous sprain, or abdominal liposuction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32335518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Morel-Lavall\u00e9e lesion (MLL) is a degloving injury in soft tissues caused by shear force accompanying trauma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32257483", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 404, "text": "A particular case of lesion in which seroma occurs is the Morel-Lavall\u00e9e lesion (MLL), which is an uncommon closed soft-tissue degloving injury that develops after high-energy trauma or crush injury where shearing forces separate the subcutaneous tissue from the underlying fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32716145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "ABSTRACT: The Morel-Lavall\u00e9e lesion (MLL) is a posttraumatic close degloving injury, which is often underdiagnosed at first.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33438963", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 261, "text": "The Morel-Lavall\u00e9e lesion (MLL) is a rare cause of pain at the knee, caused by post-traumatic shearing of the hypodermis from the underlying fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22266744", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "A Morel-Lavall\u00e9e lesion (MLL) is a posttraumatic soft-tissue injury characterized by an accumulation of blood, lymph, and other physiologic breakdown products between subcutaneous tissue and underlying fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23332912", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The Morel-Lavall\u00e9e lesion (MLL) is a rarely reported closed degloving injury, in which shearing forces have lead to break off subcutaneous tissues from the underlying fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26965645", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "INTRODUCTION: A Morel-Lavall\u00e9e lesion (MLL) is a rare and aesthetically concerning condition caused by a shearing force between subcutaneous fat and underlying fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32335518", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "INTRODUCTION: Morel-Lavall\u00e9e lesion (MLL) is a posttraumatic closed degloving soft tissue injury, in which the subcutaneous tissues are separated from the underlying fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33310472", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Morel-lavallee lesion (MLL) represents post traumatic subcutaneous cyst generally overlying bony prominences like greater trochanter, lower back, knee and scapula. A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26023620", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A Morel-Lavall\u00e9e lesion is a post-traumatic soft tissue degloving injury which presents as a haemolymphatic mass or collection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "INTRODUCTION AND IMPORTANCE: A Morel-Lavallee lesion is a closed degloving injury due to traumatic separation of the hypod", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33508615", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "The Morel-Lavall\u00e9e lesion is a closed soft-tissue degloving injury commonly associated with high-energy trauma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27579812", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "INTRODUCTION: The Morel-Lavall\u00e9e lesion is an infrequently described, post-traumatic closed de-gloving wound that results from separation of the skin and subcutaneous tissues from the underlying deep fascia as a result of shearing forces that tear perforating vessels a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30025335", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "BACKGROUND: The Morel-Lavall\u00e9e lesion is a post-traumatic collection of fluid arising after a 'closed degloving injury' has caused the separation of the skin and subcutis from the underlying musc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739602", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 419, "text": "Morel-Lavall\u00e9e lesions are the result of direct trauma or shearing forces abruptly separating skin and subcutaneous tissue from underlying fascia causing disruption of perforating vessels and nerves, creating a potential space that may fill with blood, lymph and debris forming a collection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30652431", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 814, "text": "om the mid-thigh distally. Computed tomography of the thigh demonstrated a hyperdense foci within the fluid collection suggesting internal hemorrhage and internal de-gloving suggestive of a Morel-Lavall\u00e9e lesion.DISCUSSION: The Morel-Lavall\u00e9e lesion is a post-traumatic soft tissue injury that occurs as a result of shearing forces that create a potential space for t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33217297", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "BACKGROUND: The Morel-Lavallee lesion is a closed degloving injury most commonly described in the region of the hip joint after b", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17351119", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "BACKGROUND CONTEXT: The Morel-Lavall\u00e9e lesion occurs from a compression and shear force that usually separates the skin and subcutaneous tissue from the underly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24161364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Morel-Lavallee syndrome (MLS) is a significant post-traumatic soft tissue injury in which the subcutaneous tissue is torn away from the underlying fascia (closed degloving), creating a cavity filled with hematoma and liquefied fat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24639319", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Morel-Lavall\u00e9e Lesion (MLL) is a posttraumatic, closed degloving injury where the skin and superficial fascia get separated from deep fascia (fascialata) in the trochanteric region and upper thigh, hence creating a potential space.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26506679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "The Morel-Lavall\u00e9e lesion (MLL) is a closed degloving injury caused by traumatic separation of the subcutaneous tissue from the underlying fascia, without a break in the overlying skin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30547132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "A Morel-Lavall\u00e9e lesion is a relatively rare condition involving a closed, degloving injury to the pelvis, resulting in a blood-filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20463988", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Morel-Lavall\u00e9e lesions are post-traumatic, closed degloving injuries occurring deep to subcutaneous plane due to disruption of capillaries resulting in an effusion containing hemolymph and necrotic fat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25114393", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Morel-Lavall\u00e9e lesions are cystic lesions occurring between the subcutaneous tissue and the underlying layer of a fascia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25785224", "endSection": "abstract" } ] }, { "body": "What is known about the protein patatin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33272761", "http://www.ncbi.nlm.nih.gov/pubmed/34509145" ], "ideal_answer": [ "Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 \u03bcg/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects." ], "type": "summary", "id": "6217e7a63a8413c653000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1049, "text": "Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0\u00a0\u03bcg/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33272761", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Potato patatin is considered a valuable plant protein by the food industry for its exceptional functional properties and nutritional value. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34509145", "endSection": "abstract" } ] }, { "body": "What is the mode of action of primaquine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34474834", "http://www.ncbi.nlm.nih.gov/pubmed/34216464", "http://www.ncbi.nlm.nih.gov/pubmed/4625625", "http://www.ncbi.nlm.nih.gov/pubmed/1475854", "http://www.ncbi.nlm.nih.gov/pubmed/34546758", "http://www.ncbi.nlm.nih.gov/pubmed/34257648", "http://www.ncbi.nlm.nih.gov/pubmed/1657920", "http://www.ncbi.nlm.nih.gov/pubmed/31217011", "http://www.ncbi.nlm.nih.gov/pubmed/698128", "http://www.ncbi.nlm.nih.gov/pubmed/28289025", "http://www.ncbi.nlm.nih.gov/pubmed/10501629" ], "ideal_answer": [ "Primaquine (PQ) not only eliminates P. falciparum gametocytes but also kills liver dormant forms of P. vivax and P. ovale." ], "exact_answer": [ "anti-Malarial" ], "type": "factoid", "id": "621ecac13a8413c65300005f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Primaquine (PQ) not only eliminates P. falciparum gametocytes but also kills liver dormant forms of P. vivax and P. ovale. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34257648", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 109, "text": "The effect of primaquine in preventing P. vivax relapses from dormant stages is well established.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34216464", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 132, "text": "the wide use of PQ to treat liver-stage malaria. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34546758", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 579, "text": "Primaquine (PQ) is one of the most widely used antimalarial drugs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34474834", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Low-dose primaquine is recommended to prevent Plasmodium falciparum malaria transmission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28289025", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Four amphipathic drugs, primaquine, propranolol, chlorpromazine and tetracaine, were used to cause endocytosis in glucose-depleted red cells, and the relative reduction of membrane surfaces was measured by the toluidine blue (TB) method.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/698128", "endSection": "abstract" }, { "offsetInBeginSection": 880, "offsetInEndSection": 1038, "text": "This pattern of inhibition of macromolecular biosyntheses suggests that the major in vivo action of primaquine in B. megaterium is to block protein synthesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4625625", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 441, "text": "Quinine, chloroquine, primaquine, pyrimethamine, artemesinin, mefloquine and proguanil all down-regulated the expression of monocyte receptors by 40% or greater at the therapeutic concentrations of each drug.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10501629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Mode of action of primaquine: preferential inhibition of protein biosynthesis in Bacillus megaterium.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4625625", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Mode of action of primaquine: preferential inhibition of protein biosynthesis in Bacillus megaterium", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/4625625", "endSection": "title" }, { "offsetInBeginSection": 176, "offsetInEndSection": 287, "text": " study deals with the action of primaquine, a lysosomotropic agent, on EGF-receptor complexes (EGF-RC). By the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1475854", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 620, "text": "etic analysis of primaquine inhibition indicates that its point of action is at an early step in the vesicular transport mechanism. P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1657920", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 618, "text": "Kinetic analysis of primaquine inhibition indicates that its point of action is at an early step in the vesicular transport mechanism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1657920", "endSection": "abstract" }, { "offsetInBeginSection": 390, "offsetInEndSection": 1540, "text": "n explored. Recently, new primaquine-based hybrids as new molecules with potential multi-acting anti-malarial activity were reported and two hybrids of primaquine linked to quinoxaline 1,4-di-N-oxide (PQ-QdNO) were identified as the most active against erythrocytic, exoerythrocytic and sporogonic stages.METHODS: To further understand the anti-malarial mode of action (MA) of these hybrids, hepg2-CD81 were infected with Plasmodium yoelii 17XNL and treated with PQ-QdNO hybrids during 48\u00a0h. After were evaluated the production of ROS, the mitochondrial depolarization, the total glutathione content, the DNA damage and proteins related to oxidative stress and death cell.RESULTS: In a preliminary analysis as tissue schizonticidals, these hybrids showed a mode of action dependent on peroxides production, but independent of the activation of transcription factor p53, mitochondrial depolarization and arrest cell cycle.CONCLUSIONS: Primaquine-quinoxaline 1,4-di-N-oxide hybrids exert their antiplasmodial activity in the exoerythrocytic phase by generating high levels of oxidative stress which promotes the increase of total glutathione levels, th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31217011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Primaquine blocks transport by inhibiting the formation of functional transport vesicles. Studies in a cell-free assay of protein transport through the Golgi apparatus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1657920", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Primaquine-quinoxaline 1,4-di-N-oxide hybrids with action on the exo-erythrocytic forms of Plasmodium induce their effect by the production of reactive oxygen species.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31217011", "endSection": "title" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1330, "text": "In addition to illuminating the mechanism of action of primaquine, this study suggests that the selective action of this agent will make it a useful tool in the study of the formation of transport vesicles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1657920", "endSection": "abstract" } ] }, { "body": "Which databases are devoted to 3D genome interactions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30286773", "http://www.ncbi.nlm.nih.gov/pubmed/29106613", "http://www.ncbi.nlm.nih.gov/pubmed/24526713", "http://www.ncbi.nlm.nih.gov/pubmed/27734896", "http://www.ncbi.nlm.nih.gov/pubmed/26868282" ], "ideal_answer": [ "3DIV is a 3D-genome Interaction Viewer and database. The 3D Genome Browser is a web-based browser for visualizing 3D genome organization and long-range chromatin interactions. GMOL is an Interactive Tool for 3D Genome Structure Visualization. 3Disease Browser is a Web server for integrating 3D genome and disease-associated chromosome rearrangement data. The 3DGD is a database of genome 3D structure, that currently holds Hi-C data on four species, for easy accessing and visualization of chromatin 3D structure data." ], "exact_answer": [ [ "3DIV" ], [ "3D Genome Browser" ], [ "GMOL" ], [ "3Disease Browser" ], [ "3DGD" ] ], "type": "list", "id": "5fe3131da43ad31278000049", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "3DIV: A 3D-genome Interaction Viewer and database.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29106613", "endSection": "title" }, { "offsetInBeginSection": 445, "offsetInEndSection": 696, "text": "In order to overcome these limitations, we constructed a database named 3DIV (a 3D-genome Interaction Viewer and database) that provides a list of long-range chromatin interaction partners for the queried locus with genomic and epigenomic annotations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29106613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286773", "endSection": "title" }, { "offsetInBeginSection": 6, "offsetInEndSection": 200, "text": "we introduce the 3D Genome Browser, http://3dgenome.org , which allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30286773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "GMOL: An Interactive Tool for 3D Genome Structure Visualization.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26868282", "endSection": "title" }, { "offsetInBeginSection": 496, "offsetInEndSection": 654, "text": "ere we present a desktop application, known as GMOL, designed to effectively visualize genome structures so that researchers may better analyze genomic data. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26868282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "3Disease Browser: A Web server for integrating 3D genome and disease-associated chromosome rearrangement data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27734896", "endSection": "title" }, { "offsetInBeginSection": 723, "offsetInEndSection": 898, "text": "We also develop a Web server (3Disease Browser, http://3dgb.cbi.pku.edu.cn/disease/) for integrating and visualizing disease-associated CR events and chromosomal 3D structure.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27734896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 43, "text": "The 3DGD: a database of genome 3D structure", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24526713", "endSection": "title" }, { "offsetInBeginSection": 294, "offsetInEndSection": 461, "text": "We built 3DGD (3D Genome Database), a database that currently collected Hi-C data on four species, for easy accessing and visualization of chromatin 3D structure data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24526713", "endSection": "abstract" } ] }, { "body": "Where does REGN5458 bind to?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33651100" ], "ideal_answer": [ "The bispecific antibody REGN5458 binds to B-cell maturation antigen (BCMA) and CD3." ], "exact_answer": [ [ "B-cell maturation antigen", "BCMA" ], [ "CD3" ] ], "type": "list", "id": "621218fc3a8413c653000014", "snippets": [ { "offsetInBeginSection": 183, "offsetInEndSection": 418, "text": "Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33651100", "endSection": "abstract" } ] }, { "body": "Do mutations in KCNT2 only cause phenotypes with epilepsy?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34061450" ], "ideal_answer": [ "No. There is a report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy." ], "exact_answer": "no", "type": "yesno", "id": "61f80c37882a024a1000003b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 707, "text": "KCNT2 variants resulting in substitutions affecting the Arg190 residue have been shown to cause epileptic encephalopathy and a recognizable facial gestalt. We report two additional individuals with intellectual disability, dysmorphic features, hypertrichosis, macrocephaly and the same de novo KCNT2 missense variants affecting the Arg190 residue as previously described. Notably, neither patient has epilepsy. Homology modeling of these missense variants revealed that they are likely to disrupt the stabilization of a closed channel conformation of KCNT2 resulting in a constitutively open state. This is the first report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34061450", "endSection": "abstract" } ] }, { "body": "Is there an association between pyostomatitis vegetans and Crohn's disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21305742", "http://www.ncbi.nlm.nih.gov/pubmed/27377117", "http://www.ncbi.nlm.nih.gov/pubmed/24379574", "http://www.ncbi.nlm.nih.gov/pubmed/27433081", "http://www.ncbi.nlm.nih.gov/pubmed/9747282", "http://www.ncbi.nlm.nih.gov/pubmed/27830291", "http://www.ncbi.nlm.nih.gov/pubmed/2037493", "http://www.ncbi.nlm.nih.gov/pubmed/28209014", "http://www.ncbi.nlm.nih.gov/pubmed/26864508", "http://www.ncbi.nlm.nih.gov/pubmed/8426722", "http://www.ncbi.nlm.nih.gov/pubmed/31035024", "http://www.ncbi.nlm.nih.gov/pubmed/28639684", "http://www.ncbi.nlm.nih.gov/pubmed/19242389", "http://www.ncbi.nlm.nih.gov/pubmed/9528646", "http://www.ncbi.nlm.nih.gov/pubmed/19552719", "http://www.ncbi.nlm.nih.gov/pubmed/12890215", "http://www.ncbi.nlm.nih.gov/pubmed/28958141" ], "ideal_answer": [ "Yes. Pyostomatitis vegetans (PV) is a rare condition characterized by pustules that affect the oral mucosa. It is a highly specific marker for inflammatory bowel disease and its correct recognition may lead to the diagnosis of ulcerative colitis or Crohn's disease." ], "exact_answer": "yes", "type": "yesno", "id": "61f593f8882a024a1000000f", "snippets": [ { "offsetInBeginSection": 174, "offsetInEndSection": 372, "text": "Among the main oral manifestations of IBD are cobblestoning of the oral mucosa, labial swellings with vertical fissures, pyostomatitis vegetans, angular cheilitis, perioral erythema, and glossitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26864508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Pyostomatitis Vegetans: A Clue for Diagnosis of Silent Crohn's Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28209014", "endSection": "title" }, { "offsetInBeginSection": 351, "offsetInEndSection": 614, "text": "We present a case of Pyostomatitis vegetans involving gingiva and oral mucosa with no skin lesion which led to the diagnosis of Crohn's disease to emphasize important role of dentists in diagnosis of rare oral lesions and management of patients' systemic disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28209014", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1194, "text": "Moreover, in both CD and UC, there occur several other inflammatory skin conditions such as erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, chronic oral aphthous disease, Sweet syndrome, pyostomatitis vegetans, and bowel-associated dermatosis-arthritis syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27830291", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 503, "text": "Diffuse mucosal swelling, cobblestone mucosa, localised mucogingivitis, deep linear ulceration, fibrous tissue tags, polyps, nodules, pyostomatitis vegetans, and aphthous-like ulcers have been described in Crohn's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27377117", "endSection": "abstract" }, { "offsetInBeginSection": 513, "offsetInEndSection": 610, "text": "Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 430, "text": "Pyostomatitis vegetans (PV) is a rare, chronic mucocutaneous disorder associated with inflammatory bowel disease (IBD). Oral lesions of PV are distinct and present as multiple white or yellow pustules with an erythematous base that coalesce and undergo necrosis to form a typical \"snail tracks\" appearance. Two cases of PV associated with IBD--one with Crohn's disease (CD) and the other with ulcerative colitis (UC) are reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21305742", "endSection": "abstract" }, { "offsetInBeginSection": 292, "offsetInEndSection": 481, "text": " Oral involvement during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19552719", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "Pyostomatitis vegetans (PV) is a rare condition characterized by pustules that affect the oral mucosa. It is a highly specific marker for inflammatory bowel disease and its correct recognition may lead to the diagnosis of ulcerative colitis or Crohn's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19242389", "endSection": "abstract" }, { "offsetInBeginSection": 525, "offsetInEndSection": 621, "text": "matitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD. In differe", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24379574", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 804, "text": "on-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27433081", "endSection": "abstract" }, { "offsetInBeginSection": 305, "offsetInEndSection": 493, "text": "ment during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. Starting wit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19552719", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 464, "text": "s ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their p", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28958141", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 383, "text": "e main oral manifestations of IBD are cobblestoning of the oral mucosa, labial swellings with vertical fissures, pyostomatitis vegetans, angular cheilitis, perioral erythema, and glossitis. In this sen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26864508", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 402, "text": "Pyostomatitis vegetans is frequently associated with chronic inflammatory bowel diseases and can, thus, give a diagnostic hint at an existing ulcerative colitis or Crohn\u0092s disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28639684", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Oral Crohn's disease and pyostomatitis vegetans. An unusual association.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8426722", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "[Pyostomatitis vegetans and Crohn's disease. A specific association of 2 diseases].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9528646", "endSection": "title" }, { "offsetInBeginSection": 1407, "offsetInEndSection": 1779, "text": "osis of Crohn's disease. Clinical manifestations improved dramatically with prednisone.DISCUSSION: This case of pyostomatitis-pyodermatitis vegetans involved several aspects rarely reported in the literature: a) the cutaneomucosal signs were inaugural; b) the association with Crohn's disease; c) the presence of lesions to the genital mucosa; d) the unusual localization ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9747282", "endSection": "abstract" }, { "offsetInBeginSection": 330, "offsetInEndSection": 417, "text": "Pyostomatitis vegetans is a specific marker for ulcerative colitis and Crohn's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2037493", "endSection": "abstract" }, { "offsetInBeginSection": 1280, "offsetInEndSection": 1379, "text": "The pathogenetic interrelationship between pyostomatitis vegetans and Crohn's disease is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8426722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Successful treatment with infliximab and methotrexate of pyostomatitis vegetans associated with Crohn's disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12890215", "endSection": "title" }, { "offsetInBeginSection": 536, "offsetInEndSection": 670, "text": "Infliximab and methotrexate may be a promising treatment for the rare cases of pyostomatitis vegetans associated with Crohn's disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12890215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "INTRODUCTION: Pyostomatitis vegetan (PV) is often associated with chronic inflammatory bowel disease (IBD).OBSERVATION: Tw", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31035024", "endSection": "abstract" } ] }, { "body": "Is serotonin transported by platelets?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31570504", "http://www.ncbi.nlm.nih.gov/pubmed/34662506", "http://www.ncbi.nlm.nih.gov/pubmed/32876809", "http://www.ncbi.nlm.nih.gov/pubmed/31624776", "http://www.ncbi.nlm.nih.gov/pubmed/32901992" ], "ideal_answer": [ "Yes,\nplatelets transport serotonin." ], "exact_answer": "yes", "type": "yesno", "id": "6217e1ac3a8413c653000031", "snippets": [ { "offsetInBeginSection": 231, "offsetInEndSection": 286, "text": " activated platelets, which carry peripheral serotonin,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32901992", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 879, "text": "Platelet serotonin response was measured by serotonin augmented platelet aggregation and platelet serotonin receptor density. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32876809", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 589, "text": "SERT was studied in the 1970s and 1980s using membrane vesicles isolated from blood platelets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31570504", "endSection": "abstract" }, { "offsetInBeginSection": 685, "offsetInEndSection": 847, "text": "platelet-dense granules contain neurotransmitters such as serotonin and gamma-aminobutyric acid. Molecular players controlling granule formation and secretion are", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31624776", "endSection": "abstract" }, { "offsetInBeginSection": 383, "offsetInEndSection": 461, "text": "Platelets transport and store virtually all plasma serotonin in dense granules", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34662506", "endSection": "abstract" } ] }, { "body": "Proteins in the karyopherin family (Kaps) are associated with what cellular process?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33571591", "http://www.ncbi.nlm.nih.gov/pubmed/21347375", "http://www.ncbi.nlm.nih.gov/pubmed/10385521", "http://www.ncbi.nlm.nih.gov/pubmed/11777942", "http://www.ncbi.nlm.nih.gov/pubmed/34034774", "http://www.ncbi.nlm.nih.gov/pubmed/33728352", "http://www.ncbi.nlm.nih.gov/pubmed/31487436", "http://www.ncbi.nlm.nih.gov/pubmed/17116750", "http://www.ncbi.nlm.nih.gov/pubmed/33482249", "http://www.ncbi.nlm.nih.gov/pubmed/32474299", "http://www.ncbi.nlm.nih.gov/pubmed/21029754", "http://www.ncbi.nlm.nih.gov/pubmed/33681296", "http://www.ncbi.nlm.nih.gov/pubmed/33300986", "http://www.ncbi.nlm.nih.gov/pubmed/26947076", "http://www.ncbi.nlm.nih.gov/pubmed/22357553", "http://www.ncbi.nlm.nih.gov/pubmed/11309407", "http://www.ncbi.nlm.nih.gov/pubmed/9391096", "http://www.ncbi.nlm.nih.gov/pubmed/32023817", "http://www.ncbi.nlm.nih.gov/pubmed/11735022", "http://www.ncbi.nlm.nih.gov/pubmed/15367670", "http://www.ncbi.nlm.nih.gov/pubmed/19117056" ], "ideal_answer": [ "Nuclear translocation of large proteins is mediated through specific protein carriers, collectively named karyopherins (importins, exportins and adaptor proteins)" ], "exact_answer": [ "nuclear transport" ], "type": "factoid", "id": "6221209b3a8413c653000074", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 175, "text": "Nuclear translocation of large proteins is mediated through specific protein carriers, collectively named karyopherins (importins, exportins and adaptor proteins).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33482249", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Karyopherins mediate the macromolecular transport between the cytoplasm and the nucleus and participate in cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33571591", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Transportin-1 (Trn1), also known as karyopherin-\u03b22 (Kap\u03b22), is probably the best-characterized nuclear import receptor of the karyopherin-\u03b2 family after Importin-\u03b2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33681296", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 393, "text": "Karyopherin alpha 2 (KPNA2), a member of the nuclear transporter family, is elevated in multiple human cancers and accelerates carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33728352", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "Nuclear import of proteins relies on nuclear import receptors called importins/karyopherins (Kaps), whose functions were reported in yeasts, fungi, plants, and animal cells, including cell cycle control, morphogenesis, stress sensing/response, and also fungal pathogenecity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31487436", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 365, "text": "In eukaryotic cells, nucleocytoplasmic trafficking of macromolecules is largely mediated by Karyopherin \u03b2/Importin (KPN\u03b2 or Imp\u03b2) nuclear transport factors, and they import and export cargo proteins or RNAs via the nuclear pores across the nuclear envelope, consequently effecting the cellular signal cascades in response to pathogen attack and environmental cues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32023817", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 293, "text": "The nuclear-cytoplasmic distribution of these proteins is controlled by proteins in the karyopherin family of nuclear transport factors (Kaps).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32474299", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 341, "text": "We show here that the import of histone H2A and H2B is mediated by several members of the karyopherin (Kap; importin) family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11309407", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 364, "text": "Small molecules can freely exchange through the NPC, but macromolecules larger than ~40 kDa must be aided across by transport factors, most of which belong to a related family of proteins termed karyopherins (Kaps).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22357553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11777942", "endSection": "title" }, { "offsetInBeginSection": 141, "offsetInEndSection": 254, "text": "We show here that nuclear import of TBP is mediated by a new karyopherin (Kap) (importin) family member, Kap114p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10385521", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The karyopherin (Kap) family of nuclear transport factors facilitates macromolecular transport through nuclear pore complexes (NPCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26947076", "endSection": "abstract" }, { "offsetInBeginSection": 158, "offsetInEndSection": 300, "text": "ear-cytoplasmic distribution of these proteins is controlled by proteins in the karyopherin family of nuclear transport factors (Kaps). Recent", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32474299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Human karyopherin alpha2 (KPNA2), a member of the karyopherin alpha family, plays a key role in the nuclear import of proteins with a classical nuclear localization signal (NLS). K", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11735022", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 505, "text": "ystematically manipulating the amounts, types, and affinities of Kaps and cargos, we show that import rates in vivo are simply governed by the concentrations of Kaps and their cargo and the affinity between them. These", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17116750", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Proteins in the karyopherin-\u03b2 family mediate the majority of macromolecular transport between the nucleus and the cytoplasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21029754", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "The alpha- and beta-karyopherins (Kaps), also called importins, mediate the nuclear transport of proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9391096", "endSection": "abstract" }, { "offsetInBeginSection": 487, "offsetInEndSection": 635, "text": "Karyopherins interact with nucleoporins, proteins that form the nuclear pore complex, to promote the translocation of their cargos into the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300986", "endSection": "abstract" }, { "offsetInBeginSection": 863, "offsetInEndSection": 967, "text": "Studies have also suggested that karyopherins might participate in histones deposition into nucleosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300986", "endSection": "abstract" }, { "offsetInBeginSection": 636, "offsetInEndSection": 862, "text": "When binding to histones, karyopherins not only function as nuclear import receptors but also as chaperones, protecting histones from non-specific interactions in the cytoplasm, in the nuclear pore and possibly in the nucleus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33300986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "In yeast there are at least 14 members of the beta-karyopherin protein family that govern the movement of a diverse set of cargoes between the nucleus and cytoplasm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15367670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "The Karyopherin (Kap) family of nuclear transport receptors enables trafficking of proteins to and from the nucleus in a precise, regulated manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21347375", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19117056", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "BACKGROUND: Karyopherin \u03b1-2 (KPNA2) is a member of karyopherin family, which is proved to be responsible for the import or export of cargo proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34034774", "endSection": "abstract" } ] }, { "body": "What percentage of human genes have no introns?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21914464", "http://www.ncbi.nlm.nih.gov/pubmed/22732409", "http://www.ncbi.nlm.nih.gov/pubmed/11333024", "http://www.ncbi.nlm.nih.gov/pubmed/26415210", "http://www.ncbi.nlm.nih.gov/pubmed/16469316" ], "ideal_answer": [ "About 3% of human genes have no introns. URL_0", "Intronless genes (IGs) constitute approximately 3% of the human genome. Intronless genes (IGs) fraction varies between 2.7 and 97.7% in eukaryotic genomes.", "3 percent of the human genome", "Intronless genes (IGs) constitute approximately 3% of the human genome.", "Intronless genes (IGs) constitute approximately 3% of the human genome. Intronless genes, which constitute 3 percent of the human genome, differ from intron-containing genes in evolution and function.", "Intronless genes, which constitute 3 percent of the human genome, differ from intron-containing genes in evolution and function." ], "exact_answer": [ "3%" ], "type": "factoid", "id": "5fe1fc84a43ad31278000036", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Intronless genes (IGs) constitute approximately 3% of the human genome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22732409", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Intronless genes (IGs) fraction varies between 2.7 and 97.7% in eukaryotic genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21914464", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 527, "text": "608 of these genes have intronless human orthologs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16469316", "endSection": "abstract" }, { "offsetInBeginSection": 105, "offsetInEndSection": 233, "text": "Intronless genes, which constitute 3 percent of the human genome, differ from intron-containing genes in evolution and function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26415210", "endSection": "abstract" } ] }, { "body": "What are the currently FDA approved monoclonal antibodies for myeloma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34549911" ], "ideal_answer": [ "The US Food and Drug Administration approved MoAbs, include belantamab mafodotin, daratumumab, elotuzumab, and isatuximab." ], "exact_answer": [ [ "belantamab mafodotin" ], [ "daratumumab" ], [ "elotuzumab" ], [ "isatuximab" ] ], "type": "list", "id": "62121a463a8413c653000015", "snippets": [ { "offsetInBeginSection": 400, "offsetInEndSection": 560, "text": "In this review, we highlight the current US Food and Drug Administration approved MoAbs, namely, belantamab mafodotin, daratumumab, elotuzumab, and isatuximab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34549911", "endSection": "abstract" } ] }, { "body": "What is caused by biallelic variants in PCDHGC4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34244665" ], "ideal_answer": [ "Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies." ], "exact_answer": [ "A novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies" ], "type": "factoid", "id": "61f563f7882a024a10000006", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34244665", "endSection": "title" }, { "offsetInBeginSection": 1338, "offsetInEndSection": 1541, "text": "We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34244665", "endSection": "abstract" } ] }, { "body": "Is Sotrovimab effective for COVID-19?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34531332", "http://www.ncbi.nlm.nih.gov/pubmed/34819468", "http://www.ncbi.nlm.nih.gov/pubmed/34706189", "http://www.ncbi.nlm.nih.gov/pubmed/34556486" ], "ideal_answer": [ "Yes. Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression." ], "exact_answer": "yes", "type": "yesno", "id": "61f59592882a024a10000010", "snippets": [ { "offsetInBeginSection": 2582, "offsetInEndSection": 2762, "text": "It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34531332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819468", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706189", "endSection": "title" }, { "offsetInBeginSection": 159, "offsetInEndSection": 317, "text": "Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706189", "endSection": "abstract" }, { "offsetInBeginSection": 1611, "offsetInEndSection": 1732, "text": "CONCLUSIONS: Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706189", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness.Sotrovimab is a monoclonal antibody that works directly against the spike protein of SARS-CoV-2 to block its attachment and entry into a human cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819468", "endSection": "abstract" }, { "offsetInBeginSection": 2714, "offsetInEndSection": 2901, "text": "In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34556486", "endSection": "abstract" }, { "offsetInBeginSection": 2588, "offsetInEndSection": 2767, "text": "ms that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clini", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34531332", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 77, "text": "Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34706189", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34819468", "endSection": "abstract" } ] }, { "body": "Is Otolin-1 a matrix protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29076638", "http://www.ncbi.nlm.nih.gov/pubmed/28498270", "http://www.ncbi.nlm.nih.gov/pubmed/20856818", "http://www.ncbi.nlm.nih.gov/pubmed/18410381" ], "ideal_answer": [ "Yes,\notolin-1 is a otoconia matrix protein." ], "exact_answer": "yes", "type": "yesno", "id": "621b5bcc3a8413c65300003d", "snippets": [ { "offsetInBeginSection": 138, "offsetInEndSection": 171, "text": "otoconia matrix protein, otolin-1", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28498270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Otolin-1 is a collagen-like protein expressed in the inner ear of vertebrates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29076638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Mammalian Otolin: a multimeric glycoprotein specific to the inner ear that interacts with otoconial matrix protein Otoconin-90 and Cerebellin-1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20856818", "endSection": "title" }, { "offsetInBeginSection": 1558, "offsetInEndSection": 1616, "text": "binds to otolin-1 and forming matrix protein architectures", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18410381", "endSection": "abstract" } ] }, { "body": "List the drug targets of Faricimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34511878", "http://www.ncbi.nlm.nih.gov/pubmed/30905643", "http://www.ncbi.nlm.nih.gov/pubmed/34188445", "http://www.ncbi.nlm.nih.gov/pubmed/32785136", "http://www.ncbi.nlm.nih.gov/pubmed/31513439", "http://www.ncbi.nlm.nih.gov/pubmed/32342814", "http://www.ncbi.nlm.nih.gov/pubmed/33471572", "http://www.ncbi.nlm.nih.gov/pubmed/32729897", "http://www.ncbi.nlm.nih.gov/pubmed/32729888" ], "ideal_answer": [ "Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2.", "Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2" ], "exact_answer": [ [ "VEGF-A" ], [ "Ang-2" ] ], "type": "list", "id": "621eb93b3a8413c65300005b", "snippets": [ { "offsetInBeginSection": 438, "offsetInEndSection": 541, "text": "Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31513439", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 311, "text": "Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34511878", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 374, "text": "Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34511878", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 425, "text": "Faricimab is a promising bispecific drug targeting VEGF-A and the Ang-Tie/pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33471572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33471572", "endSection": "title" }, { "offsetInBeginSection": 952, "offsetInEndSection": 1148, "text": "Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32785136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "This review focuses on 5 new anti-VEGF drugs in the advanced stage of clinical development (i.e., phase 3): conbercept, brolucizumab, port delivery system with ranibizumab, abicipar pegol and faricimab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32342814", "endSection": "abstract" }, { "offsetInBeginSection": 1097, "offsetInEndSection": 1299, "text": "Faricimab is a bispecific anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34188445", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "Importance: Faricimab, the first bispecific antibody designed for intraocular use, simultaneously and independently binds and neutralizes angiopoietin 2 (Ang-2) and vascular endothelial growth factor A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32729888", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 417, "text": "gimen. Faricimab is a promising bispecific drug targeting VEGF-A and the Ang-Tie/", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33471572", "endSection": "abstract" }, { "offsetInBeginSection": 977, "offsetInEndSection": 1174, "text": "ntified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32785136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "PURPOSE: The phase 2 BOULEVARD trial compared safety and efficacy of faricimab, a novel bispecific antibody targeting angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A), with ranibizumab in patients with diabetic macular edema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30905643", "endSection": "abstract" }, { "offsetInBeginSection": 422, "offsetInEndSection": 526, "text": " Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials fo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31513439", "endSection": "abstract" }, { "offsetInBeginSection": 1121, "offsetInEndSection": 1323, "text": "c anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing. PAN-90806 is a topical ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34188445", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 541, "text": "Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31513439", "endSection": "abstract" }, { "offsetInBeginSection": 1149, "offsetInEndSection": 1512, "text": "By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32785136", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 933, "text": "PURPOSE: The phase 2 BOULEVARD trial compared safety and efficacy of faricimab, a novel bispecific antibody targeting angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A), with ranibizumab in patients with diabetic macular edema (DME).DESIGN: The BOULEVARD trial (ClinicalTrials.gov identifier, NCT02699450) was a prospective, randomized, active comparator-controlled, double-masked, multicenter, phase 2 study conducted at 59 sites in the United States.PARTICIPANTS: The trial enrolled patients 18 years of age or older with center-involving DME, best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central subfield thickness (CST) of 325 \u03bcm or more.METHODS: Anti-VEGF treatment-na\u00efve patients were randomized 1:1:1 to intravitreal 6.0 mg faricimab, 1.5 mg faricimab, or 0.3 mg ranibizumab, and patients previously treated with anti-VEGF were randomized 1:1 to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30905643", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 529, "text": "Importance: Faricimab, the first bispecific antibody designed for intraocular use, simultaneously and independently binds and neutralizes angiopoietin 2 (Ang-2) and vascular endothelial growth factor A (VEGF-A).Objective: To assess the efficacy and safety of different doses and regimens of faricimab vs ranibizumab in patients with neovascular age-related macular degeneration (nAMD).Design, Setting, and Participants: AVENUE was a 36-week, multiple-dose-regimen, active comparator-controlled, double-masked, phase 2 randomized ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32729888", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 407, "text": "Importance: Faricimab neutralizes angiopoietin-2 and vascular endothelial growth factor A via both simultaneous and independent binding.Objective: To evaluate extended dosing with faricimab, the first bispecific antibody designed for intraocular use, in patients with neovascular age-related macular degeneration.Design, Setting, and Participants: This phase 2 randomized clinical trial was a 52-week multic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32729897", "endSection": "abstract" } ] }, { "body": "What induces downstream of gene (DoG) readthrough transcription?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28928151", "http://www.ncbi.nlm.nih.gov/pubmed/9343185", "http://www.ncbi.nlm.nih.gov/pubmed/30089468", "http://www.ncbi.nlm.nih.gov/pubmed/29945683", "http://www.ncbi.nlm.nih.gov/pubmed/26861889", "http://www.ncbi.nlm.nih.gov/pubmed/29147672", "http://www.ncbi.nlm.nih.gov/pubmed/29548296" ], "ideal_answer": [ "Stress-induced transcriptional readthrough generates very long downstream of gene containing transcripts (DoGs), which may explain up to 20% of intergenic transcription. Massive induction of transcriptional readthrough generates downstream of gene-containing transcripts (DoGs) in cells under stress condition. Ca2+ signaling mediates reduced transcription termination in response to certain stress conditions. This reduction allows readthrough transcription, generating a highly inducible and diverse class of downstream of gene containing transcripts (DoGs) that we have recently described.", "osmotic stress", "DoGs are induced by osmotic stress at the level of transcription by a mechanism that depends on calcium release from the endoplasmic reticulum mediated by IP3 receptors." ], "exact_answer": [ "stress conditions" ], "type": "factoid", "id": "5fe31316a43ad31278000043", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Readthrough activation of early adenovirus E1b gene transcription", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9343185", "endSection": "title" }, { "offsetInBeginSection": 429, "offsetInEndSection": 560, "text": "Using the rigorous methodology Cap-Seq, we demonstrated that DoGs result from transcriptional readthrough, not de novo initiation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29945683", "endSection": "abstract" }, { "offsetInBeginSection": 1662, "offsetInEndSection": 1771, "text": "Rather it is, as we originally demonstrated, transcriptional readthrough that leads to the formation of DoGs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29945683", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "Previous studies demonstrated that massive induction of transcriptional readthrough generates downstream of gene-containing transcripts (DoGs) in cells under stress condition", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29548296", "endSection": "abstract" }, { "offsetInBeginSection": 618, "offsetInEndSection": 913, "text": " Importantly, Ca2+ signaling mediates reduced transcription termination in response to certain stress conditions. This reduction allows readthrough transcription, generating a highly inducible and diverse class of downstream of gene containing transcripts (DoGs) that we have recently described.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29147672", "endSection": "abstract" }, { "offsetInBeginSection": 1598, "offsetInEndSection": 1843, "text": "Finally, we examine genomic features of readthrough transcription and observe a unique chromatin signature typical of DoG-producing regions, suggesting that readthrough transcription is associated with the maintenance of an open chromatin state.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28928151", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 647, "text": "We recently discovered that stress-induced transcriptional readthrough generates very long downstream of gene containing transcripts (DoGs), which may explain up to 20% of intergenic transcription. DoGs are induced by osmotic stress at the level of transcription by a mechanism that depends on calcium release from the endoplasmic reticulum mediated by IP3 receptors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26861889", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 658, "text": "Furthermore, the readthrough response to stress has thus far not been investigated outside of mammalian species, and the occurrence of readthrough in many physiological and disease conditions remains to be explored", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30089468", "endSection": "abstract" }, { "offsetInBeginSection": 1171, "offsetInEndSection": 1403, "text": "We further demonstrate the use of the DoGFinder software package on a new publically available RNA-seq dataset, and discover DoG induction in human PME cells following hypoxia - a previously unknown readthrough inducing stress type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30089468", "endSection": "abstract" } ] }, { "body": "What is the effect of rHDL-apoE3 on endothelial cell migration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34875308" ], "ideal_answer": [ "rHDL-apoE3 has been shown to promote endothelial cell migration." ], "exact_answer": [ "Promotion" ], "type": "factoid", "id": "6206b5a8c9dfcb9c0900003a", "snippets": [ { "offsetInBeginSection": 3531, "offsetInEndSection": 3690, "text": "These novel insights into the rHDL-apoE3 functions suggest a potential clinical use to promote re-endothelialization and retard development of atherosclerosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34875308", "endSection": "abstract" }, { "offsetInBeginSection": 1245, "offsetInEndSection": 1632, "text": "The capacity of rHDL-apoE3 to stimulate EC migration was assessed by wound healing and transwell migration assays. The contribution of MEK1/2, PI3K and the transcription factor ID1 in rHDL-apoE3-induced EC migration and activation of EC migration-related effectors was assessed using specific inhibitors (PD98059: MEK1/2, LY294002: PI3K) and siRNA-mediated gene silencing, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34875308", "endSection": "abstract" }, { "offsetInBeginSection": 2436, "offsetInEndSection": 2591, "text": "In addition, rHDL-apoE3 stimulated migration of HCAEC and EA.hy926 cells, and the migration was markedly attenuated in the presence of PD98059 or LY294002.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34875308", "endSection": "abstract" } ] }, { "body": "Is AGO2 related to cytokinesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34117353" ], "ideal_answer": [ "Yes. AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division." ], "exact_answer": "yes", "type": "yesno", "id": "620aedee3a8413c653000001", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34117353", "endSection": "title" }, { "offsetInBeginSection": 871, "offsetInEndSection": 1037, "text": "We suggest that AGO2 is part of a regulatory mechanism triggered by cytokinetic stress to generate the appropriate micro-environment for local transcript homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34117353", "endSection": "abstract" } ] }, { "body": "Hampton\u2019s hump is characteristic to which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24862753", "http://www.ncbi.nlm.nih.gov/pubmed/8372182", "http://www.ncbi.nlm.nih.gov/pubmed/26521192" ], "ideal_answer": [ "Hampton\u2019s hump is characteristic to pulmonary embolism." ], "exact_answer": [ "pulmonary embolism" ], "type": "factoid", "id": "61f5ee57882a024a10000012", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Hampton's hump in a patient with endocarditis and septic emboli.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26521192", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 347, "text": "We discuss a case of a 20-year-old woman presenting with chest pain found to have a Hampton's hump on chest x-ray and corresponding wedge infarct on computed tomographic scan. Contrary to our suspicion that this febrile and tachycardic patient had a pulmonary embolism, she was later determined to have a septic embolus secondary to endocarditis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26521192", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 566, "text": "Chest radiograph showed a peripheral-based opacity in the right lower zone, which was not seen in a previous study done three months ago, suggestive of Hampton's hump. The D-dimer level was raised. Computed tomography pulmonary angiography confirmed the diagnosis of pulmonary embolism in a right lower lobe segmental branch, with adjacent collapsed lung, consistent with lung infarction. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24862753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 175, "text": "We discuss a case of a 20-year-old woman presenting with chest pain found to have a Hampton's hump on chest x-ray and corresponding wedge infarct on computed tomographic scan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26521192", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 933, "text": "emia (the Westermark sign), prominent central pulmonary artery (the Fleischner sign), pleural-based area of increased opacity (the Hampton hump), vascular redistribution, pleural effusion, elevated diaphragm, and enlarged hilum were also poor predictors of PE.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8372182", "endSection": "abstract" }, { "offsetInBeginSection": 624, "offsetInEndSection": 1100, "text": "ferent from that in patients without PE. Oligemia (the Westermark sign), prominent central pulmonary artery (the Fleischner sign), pleural-based area of increased opacity (the Hampton hump), vascular redistribution, pleural effusion, elevated diaphragm, and enlarged hilum were also poor predictors of PE.CONCLUSION: Although chest radiographs are essential in the investigation of suspected PE, their main value is to exclude diagnoses that clinically mimic PE and to aid in ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8372182", "endSection": "abstract" } ] }, { "body": "What is the activity of Indoleamine 2,3-dioxygenase 1.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34535017", "http://www.ncbi.nlm.nih.gov/pubmed/34520819", "http://www.ncbi.nlm.nih.gov/pubmed/34752953", "http://www.ncbi.nlm.nih.gov/pubmed/34557196" ], "ideal_answer": [ "Indoleamine 2,3-dioxygenase 1 (IDO1), a known immunosuppressive enzyme that catalyzes the rate-limiting step in the oxidation of tryptophan (Trp) to kynurenine (Kyn), has received increasing attention as an attractive immunotherapeutic target for cancer therapy." ], "exact_answer": [ "Immunosuppressive activity" ], "type": "factoid", "id": "6217d9493a8413c653000022", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 263, "text": "Indoleamine 2,3-dioxygenase 1 (IDO1), a known immunosuppressive enzyme that catalyzes the rate-limiting step in the oxidation of tryptophan (Trp) to kynurenine (Kyn), has received increasing attention as an attractive immunotherapeutic target for cancer therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34752953", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 273, "text": "Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn) in kynurenine pathway (KP) is involved in the immunosuppression in pancreatic cancer (PC), but the value of IDO1 as an independent prognostic marker for PC is uncertain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34520819", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 341, "text": "Indoleamine 2,3-dioxygenase 1 (IDO1), which is negatively regulated by the BIN1 proto-oncogene, is an interferon (IFN)-\u03b3-inducible mediator of immune tolerance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535017", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 220, "text": "Indoleamine 2,3-dioxygenase 1 (IDO1) is a normal endogenous mechanism of acquired peripheral immune tolerance and may therefore be tumor-promoting. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34557196", "endSection": "abstract" } ] }, { "body": "What is the purpose of Macropinocytosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30967003", "http://www.ncbi.nlm.nih.gov/pubmed/33520357", "http://www.ncbi.nlm.nih.gov/pubmed/30967006", "http://www.ncbi.nlm.nih.gov/pubmed/30967007", "http://www.ncbi.nlm.nih.gov/pubmed/30967008", "http://www.ncbi.nlm.nih.gov/pubmed/30967009", "http://www.ncbi.nlm.nih.gov/pubmed/30400219", "http://www.ncbi.nlm.nih.gov/pubmed/32756454", "http://www.ncbi.nlm.nih.gov/pubmed/10678991", "http://www.ncbi.nlm.nih.gov/pubmed/25096879", "http://www.ncbi.nlm.nih.gov/pubmed/10321993", "http://www.ncbi.nlm.nih.gov/pubmed/11029048", "http://www.ncbi.nlm.nih.gov/pubmed/11890548", "http://www.ncbi.nlm.nih.gov/pubmed/15533943", "http://www.ncbi.nlm.nih.gov/pubmed/32745890", "http://www.ncbi.nlm.nih.gov/pubmed/31924779", "http://www.ncbi.nlm.nih.gov/pubmed/34755081", "http://www.ncbi.nlm.nih.gov/pubmed/30617109", "http://www.ncbi.nlm.nih.gov/pubmed/30333835", "http://www.ncbi.nlm.nih.gov/pubmed/30966999", "http://www.ncbi.nlm.nih.gov/pubmed/27352861", "http://www.ncbi.nlm.nih.gov/pubmed/29085336", "http://www.ncbi.nlm.nih.gov/pubmed/14732047", "http://www.ncbi.nlm.nih.gov/pubmed/27503856", "http://www.ncbi.nlm.nih.gov/pubmed/30725454", "http://www.ncbi.nlm.nih.gov/pubmed/27647881", "http://www.ncbi.nlm.nih.gov/pubmed/17760832" ], "ideal_answer": [ "Macropinocytosis is an endocytic process, which involves the engulfment of extra-cellular content in vesicles known as macropinosomes." ], "exact_answer": [ "transport across an external cell membrane" ], "type": "factoid", "id": "62211ebc3a8413c653000071", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "Macropinocytosis defines a series of events initiated by extensive plasma membrane reorganization or ruffling to form an external macropinocytic structure that is then enclosed and internalized. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17760832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Macropinocytosis is a form of endocytosis that accompanies cell surface ruffling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14732047", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 75, "text": "Modified LDLs are internalized by macrophages in part via macropinocytosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10321993", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Macropinocytosis results from the closure of lamellipodia generated by membrane ruffling, thereby reflecting cortical actin dynamics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11029048", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Gonococcal entry into primary human urethral epithelial cells (HUEC) can occur by macropinocytosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10678991", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Macropinocytosis as a mechanism of entry into primary human urethral epithelial cells by Neisseria gonorrhoeae.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10678991", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "Macropinocytosis is a normal cellular process by which cells internalize extracellular fluids and nutrients from their environment and is one strategy that Ras-transformed pancreatic cancer cells use to increase uptake of amino acids to meet the needs of rapid growth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27503856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Macropinocytosis is a regulated form of endocytosis that mediates the nonselective uptake of nutrients to support growth under nutrient-deprived conditions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30400219", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Macropinocytosis is an ancient mechanism that allows cells to harvest nutrients from extracellular media, which also allows immune cells to sample antigens from their surroundings.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27647881", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "Macropinocytosis refers to the non-specific uptake of extracellular fluid, which plays ubiquitous roles in cell growth, immune surveillance, and virus entry. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34755081", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Macropinocytosis has emerged as an important nutrient supply pathway that sustains cell growth of cancer cells within the nutrient-poor tumor microenvironment", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30725454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30966999", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Macropinocytosis is an actin-driven process of large-scale and non-specific fluid uptake used for feeding by some cancer cells and the macropinocytosis model organism Dictyostelium discoideum In Dictyostelium, macropinocytic cups are organized by 'macropin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30617109", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Macropinocytosis-the large-scale, non-specific uptake of fluid by cells-is used by Dictyostelium discoideum amoebae to obtain nutrients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30967009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Macropinocytosis has received increasing attention in recent years for its various roles in nutrient acquisition, immune surveillance, and virus and cancer pathologies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30333835", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Macropinocytosis is an evolutionarily-conserved, large-scale, fluid-phase form of endocytosis that has been ascribed different functions including antigen presentation in macrophages and dendritic cells, regulation of receptor density in neurons, and regulation of tumor growth under nutrient-limiting conditions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31924779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Macropinocytosis is an evolutionarily conserved form of endocytosis that mediates non-selective uptake of extracellular fluid and the solutes contained therein.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30967008", "endSection": "abstract" }, { "offsetInBeginSection": 519, "offsetInEndSection": 796, "text": "The primary function of macropinocytosis in amoebae and some cancer cells is feeding, but the conserved processing pathway for macropinosomes, which involves shrinkage and the retrieval of membrane to the cell surface, has been adapted in immune cells for antigen presentation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30967007", "endSection": "abstract" }, { "offsetInBeginSection": 1372, "offsetInEndSection": 1513, "text": "Macropinocytosis is induced by many pathogens to enter host cells, but other functions for macropinocytosis in virus replication are unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25096879", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Macropinocytosis is a means by which eukaryotic cells ingest extracellular liquid and dissolved molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27352861", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Macropinocytosis is the endocytic pathway that mediates macrophage foam cell formation with native low density lipoprotein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15533943", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Macropinocytosis refers to the formation of primary large endocytic vesicles of irregular size and shape, generated by actin-driven evaginations of the plasma membrane, whereby cells avidly incorporate extracellular fluid.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11890548", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Macropinocytosis is exploited by many pathogens for entry into cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25096879", "endSection": "abstract" }, { "offsetInBeginSection": 614, "offsetInEndSection": 919, "text": "This suggests that macropinocytosis is necessary for mTORC1-dependent growth of metazoan cells, both as a route for delivery of amino acids to sensors associated with lysosomes and as a platform for growth factor-dependent signalling to mTORC1 via phosphatidylinositol 3-kinase (PI3K) and the Akt pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30967006", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Macropinocytosis is a form of endocytosis which provides an effective way for non-selective uptakes of extracellular proteins, liquids, and particles.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33520357", "endSection": "abstract" }, { "offsetInBeginSection": 216, "offsetInEndSection": 390, "text": "Macropinocytosis is important in a range of physiological processes, including antigen presentation, nutrient sensing, recycling of plasma proteins, migration and signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32756454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "Macropinocytosis is increasingly recognized for its versatile adaptations and functions as a highly conserved, ubiquitous pathway for the bulk uptake of fluid, particulate cargo, and membranes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32745890", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "In tumour cells, macropinocytosis functions as an amino acid supply route and supports cancer cell survival and proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30967003", "endSection": "abstract" }, { "offsetInBeginSection": 351, "offsetInEndSection": 526, "text": "Macropinocytosis is an evolutionarily conserved endocytic pathway that permits the internalization of extracellular fluid via large endocytic vesicles known as macropinosomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29085336", "endSection": "abstract" }, { "offsetInBeginSection": 527, "offsetInEndSection": 646, "text": "Recently, macropinocytosis has been determined to function as a nutrient-scavenging pathway in Ras-driven cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29085336", "endSection": "abstract" } ] }, { "body": "Which was the first species in which a de novo gene emergence (\"gene birth\") was reported?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25506301", "http://www.ncbi.nlm.nih.gov/pubmed/29556078", "http://www.ncbi.nlm.nih.gov/pubmed/28943376", "http://www.ncbi.nlm.nih.gov/pubmed/27358863", "http://www.ncbi.nlm.nih.gov/pubmed/28642936", "http://www.ncbi.nlm.nih.gov/pubmed/29216381", "http://www.ncbi.nlm.nih.gov/pubmed/28325876", "http://www.ncbi.nlm.nih.gov/pubmed/30346517", "http://www.ncbi.nlm.nih.gov/pubmed/24391509", "http://www.ncbi.nlm.nih.gov/pubmed/27056411", "http://www.ncbi.nlm.nih.gov/pubmed/22722833", "http://www.ncbi.nlm.nih.gov/pubmed/27103098" ], "ideal_answer": [ "New genes can arise through duplication of a pre-existing gene or de novo from non-coding DNA, providing raw material for evolution of new functions in response to a changing environment. A prime example is the independent evolution of antifreeze glycoprotein genes (afgps) in the Arctic codfishes and Antarctic notothenioids to prevent freezing." ], "exact_answer": [ "the Arctic codfish" ], "type": "factoid", "id": "5eb422150d431b5f73000009", "snippets": [ { "offsetInBeginSection": 239, "offsetInEndSection": 474, "text": "de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722833", "endSection": "abstract" }, { "offsetInBeginSection": 668, "offsetInEndSection": 855, "text": "Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722833", "endSection": "abstract" }, { "offsetInBeginSection": 1178, "offsetInEndSection": 1351, "text": "We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22722833", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 383, "text": "Although the origin of such \"orphan\" genes remains unclear, they are thought to be involved in species-specific adaptive processes. Here, we analyzed seven orphan genes (MoSPC1 to MoSPC7) prioritized based on in planta expressed sequence tag data in the rice blast fungus, Magnaporthe oryzae.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506301", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1298, "text": "Based on these results, the four orphan genes may be products of de novo gene birth processes, and their adaptive potential is in the course of being tested for retention or extinction through natural selection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25506301", "endSection": "abstract" }, { "offsetInBeginSection": 1741, "offsetInEndSection": 1926, "text": "NCYM is the first de novo evolved protein known to act as an oncopromoting factor in human cancer, and suggest that de novo evolved proteins may functionally characterize human disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24391509", "endSection": "abstract" }, { "offsetInBeginSection": 2580, "offsetInEndSection": 2723, "text": "De novo gene-birth contributes to shorter exons, longer introns, and higher exon-density in species-specific genes relative to conserved genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27358863", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "The phenomenon of de novo gene birth from junk DNA is surprising, because random polypeptides are expected to be toxic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28642936", "endSection": "abstract" }, { "offsetInBeginSection": 919, "offsetInEndSection": 1072, "text": "These targets regulated diverse biological processes including nutrient sensing and the DNA damage response, and implicated Vts1 in de novo gene \"birth.\"", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28325876", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 425, "text": "Many modern analysis pipelines use significant sequence similarity scores (p- or E-values) and the ranked order of BLAST matches to test a wide range of hypotheses concerning homology, orthology, the timing of de novo gene birth/death and gene family", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27103098", "endSection": "abstract" }, { "offsetInBeginSection": 27, "offsetInEndSection": 139, "text": "The Majority of Novel Protein-Coding Genes Identified with Phylostratigraphy Are Old Genes or Recent Duplicates.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346517", "endSection": "title" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1188, "text": "Using a combination of synteny information and sequence similarity searches, I show that \u223c60% of the remaining 381 putative de novo genes share homology with genes from other vertebrates, originated through gene duplication, and/or share no synteny information with nonrodent mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30346517", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 728, "text": "We find hundreds of open reading frames that are translated and that show no evolutionary conservation or selective constraints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29556078", "endSection": "abstract" }, { "offsetInBeginSection": 318, "offsetInEndSection": 523, "text": " The AQP2 gene consists of four exons, but the alternative AQP2 gene lacks the fourth exon and instead has a longer third exon that includes the original third exon and a part of the original third intron.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28943376", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 771, "text": "Nonetheless we identified 35 de novo genes: 16 human-specific; 5 human and chimpanzee specific; and 14 that originated prior to the divergence of human, chimpanzee, and gorilla and are found in all three genomes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27056411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "De novo gene evolution of antifreeze glycoproteins in codfishes revealed by whole genome sequence data.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29216381", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "New genes can arise through duplication of a pre-existing gene or de novo from non-coding DNA, providing raw material for evolution of new functions in response to a changing environment. A prime example is the independent evolution of antifreeze glycoprotein genes (afgps) in the Arctic codfishes and Antarctic notothenioids to prevent freezing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29216381", "endSection": "abstract" } ] }, { "body": "What are chromones?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24925412" ], "ideal_answer": [ "The chromones are a class of chemical compounds characterised by the presence of the structure 5:6 benz-1:4-pyrone in their chemical make-up." ], "type": "summary", "id": "6206c428c9dfcb9c0900003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The chromones are a class of chemical compounds characterised by the presence of the structure 5:6 benz-1:4-pyrone in their chemical make-up. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925412", "endSection": "abstract" } ] }, { "body": "Which type of cancer has been suggested as a strategy for potential small-molecule inhibition of METTL3?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33902106" ], "ideal_answer": [ "Small-molecule inhibition of METTL3 is a strategy against myeloid leukaemia. Targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy.", "Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia." ], "exact_answer": [ "myeloid leukaemia" ], "type": "factoid", "id": "620c28d03a8413c653000007", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33902106", "endSection": "title" }, { "offsetInBeginSection": 358, "offsetInEndSection": 1306, "text": "Here we present the identification and characterization of STM2457, a highly potent and selective first-in-class catalytic inhibitor of METTL3, and a crystal structure of STM2457 in complex with METTL3-METTL14. Treatment of tumours with STM2457 leads to reduced AML growth and an increase in differentiation and apoptosis. These cellular effects are accompanied by selective reduction of m6A levels on known leukaemogenic mRNAs and a decrease in their expression consistent with a translational defect. We demonstrate that pharmacological inhibition of METTL3 in vivo leads to impaired engraftment and prolonged survival in various mouse models of AML, specifically targeting key stem cell subpopulations of AML. Collectively, these results reveal the inhibition of METTL3 as a potential therapeutic strategy against AML, and provide proof of concept that the targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33902106", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Lanifibranor?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32613381", "http://www.ncbi.nlm.nih.gov/pubmed/29446942", "http://www.ncbi.nlm.nih.gov/pubmed/33038502", "http://www.ncbi.nlm.nih.gov/pubmed/32360434", "http://www.ncbi.nlm.nih.gov/pubmed/33987427", "http://www.ncbi.nlm.nih.gov/pubmed/33278455", "http://www.ncbi.nlm.nih.gov/pubmed/34670042", "http://www.ncbi.nlm.nih.gov/pubmed/30261763", "http://www.ncbi.nlm.nih.gov/pubmed/34488870" ], "ideal_answer": [ "Lanifibranor is peroxisome proliferator-activated receptor (PPAR) agonist." ], "type": "summary", "id": "61f5f580882a024a10000017", "snippets": [ { "offsetInBeginSection": 683, "offsetInEndSection": 936, "text": "These cell systems were then used to evaluate the anti-NASH properties of eight peroxisome proliferator-activated receptor (PPAR) agonists (bezafibrate, elafibranor, fenofibrate, lanifibranor, pemafibrate, pioglitazone, rosiglitazone, and saroglitazar).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32613381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34488870", "endSection": "title" }, { "offsetInBeginSection": 210, "offsetInEndSection": 408, "text": "We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34488870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33278455", "endSection": "title" }, { "offsetInBeginSection": 289, "offsetInEndSection": 545, "text": "Given the current lack of an effective treatment, we aimed to characterise the effects of the pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor in 2 preclinical models of ACLD, as well as in liver cells from patients with ACLD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33278455", "endSection": "abstract" }, { "offsetInBeginSection": 721, "offsetInEndSection": 1072, "text": "This explains the manifold metabolic pathways as antifibrotic targets, including farnesoid X receptor (FXR) agonism (obeticholic acid, nonsteroidal FXR agonists), acetyl-CoA carboxylase inhibition, peroxisome proliferator-activator receptor agonism (elafibranor, lanifibranor, saroglitazar), and fibroblast growth factor (FGF)-21 or FGF-19 activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30261763", "endSection": "abstract" }, { "offsetInBeginSection": 1586, "offsetInEndSection": 1987, "text": "While several promising drug candidates failed in phase 2 or 3 clinical trials (including elafibranor, emricasan and selonsertib), promising results with the farnesoid X receptor agonist obeticholic acid, the pan-PPAR agonist lanifibranor and the chemokine receptor CCR2/CCR5 inhibitor cenicriviroc support the expectation of an effective pharmacological therapy for liver fibrosis in the near future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33987427", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 473, "text": "Starting with a PPAR\u03b1 activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29446942", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 602, "text": "Lanifibranor (IVA337), a panPPAR agonist, by acting on these three different PPAR isotypes, combines pharmacological effects that could address the different components of the disease as demonstrated in preclinical models.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33038502", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 265, "text": "Lanifibranor is a pan-PPAR (peroxisome proliferator-activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34670042", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34670042", "endSection": "title" }, { "offsetInBeginSection": 79, "offsetInEndSection": 258, "text": "cal need. Lanifibranor is a pan-PPAR (peroxisome proliferator-activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34670042", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 490, "text": "nical need. Lanifibranor is a pan-PPAR (peroxisome proliferator-activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH.METHODS: In this phase 2b, double-blind, randomized, placebo-controlled trial, patients with noncirrhotic, highly active NASH were randomly assigned in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo onc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34670042", "endSection": "abstract" }, { "offsetInBeginSection": 1694, "offsetInEndSection": 2057, "text": "a metabolically activated phenotype. Lanifibranor attenuated the accompanying inflammatory activation in both murine palmitic acid-stimulated bone marrow-derived macrophages, as well as patient-derived circulating monocytes, in a PPAR\u03b4-dependent fashion.CONCLUSION: Pan-PPAR agonists combine the beneficial effects of selective PPAR agonists and may counteract in", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32360434", "endSection": "abstract" }, { "offsetInBeginSection": 2058, "offsetInEndSection": 2334, "text": "lammation and disease progression more potently. PPAR\u03b4 agonism and lanifibranor directly modulate macrophage activation, but not infiltration, thereby synergizing with beneficial metabolic effects of PPAR\u03b1/\u03b3 agonists.LAY SUMMARY: Peroxisome proliferated-activated receptors (P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32360434", "endSection": "abstract" } ] }, { "body": "Is the protein HOXA11 associated with endometrial disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33419445", "http://www.ncbi.nlm.nih.gov/pubmed/34844098", "http://www.ncbi.nlm.nih.gov/pubmed/33515421", "http://www.ncbi.nlm.nih.gov/pubmed/32347039" ], "ideal_answer": [ "Yes,\nLow HOXA11 expression may promote the proliferation, migration, invasion of endometrial cancer cells" ], "exact_answer": "yes", "type": "yesno", "id": "621b61833a8413c65300003e", "snippets": [ { "offsetInBeginSection": 487, "offsetInEndSection": 571, "text": " Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34844098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Combined expression of HOXA11 and CD10 identifies endometriosis versus normal tissue and tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34844098", "endSection": "title" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1565, "text": "The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34844098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Downregulation of HOXA11 enhances endometrial cancer malignancy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33515421", "endSection": "title" }, { "offsetInBeginSection": 1583, "offsetInEndSection": 1764, "text": "Low HOXA11 expression may promote the proliferation, migration, invasion of endometrial cancer cells, and increase their resistance to cisplatin through activating PTEN/AKT pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33515421", "endSection": "abstract" }, { "offsetInBeginSection": 923, "offsetInEndSection": 1061, "text": "Endometrial mRNA and protein expression levels of HOXA10 and HOXA11 were significantly lower in patients with AM than in control patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33419445", "endSection": "abstract" } ] }, { "body": "Summarize the function of DEAH helicase DHX36 and its role in G-quadruplex-dependent processes.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29899445", "http://www.ncbi.nlm.nih.gov/pubmed/33857359", "http://www.ncbi.nlm.nih.gov/pubmed/33857358", "http://www.ncbi.nlm.nih.gov/pubmed/34862880", "http://www.ncbi.nlm.nih.gov/pubmed/33021960", "http://www.ncbi.nlm.nih.gov/pubmed/34025941", "http://www.ncbi.nlm.nih.gov/pubmed/29269411", "http://www.ncbi.nlm.nih.gov/pubmed/30910870", "http://www.ncbi.nlm.nih.gov/pubmed/25653156", "http://www.ncbi.nlm.nih.gov/pubmed/27797375" ], "ideal_answer": [ "DEAH-Box helicase 36 (DHX36), a member of the large DExD/H box helicase family, enzymatically unwinds both G4 DNA and G4 RNA. RNA helicases of the DEAH/RHA family form a large and conserved class of enzymes that remodel RNA protein complexes (RNPs) by translocating along the RNA" ], "type": "summary", "id": "6220cf383a8413c653000069", "snippets": [ { "offsetInBeginSection": 286, "offsetInEndSection": 410, "text": "DEAH-Box helicase 36 (DHX36), a member of the large DExD/H box helicase family, enzymatically unwinds both G4 DNA and G4 RNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34862880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "RNA helicases of the DEAH/RHA family form a large and conserved class of enzymes that remodel RNA protein complexes (RNPs) by translocating along the RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33857358", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "DHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33021960", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 365, "text": " G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33021960", "endSection": "abstract" }, { "offsetInBeginSection": 531, "offsetInEndSection": 701, "text": "We also show that GSEC binds to the DEAH box polypeptide 36 (DHX36) RNA helicase via its G-quadruplex-forming sequence and inhibits DHX36 G-quadruplex unwinding activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27797375", "endSection": "abstract" }, { "offsetInBeginSection": 168, "offsetInEndSection": 293, "text": "DHX36, also known as RHAU or G4R1, is a DEAH-box ATP-dependent helicase highly specific for DNA and RNA G-quadruplexes (G4s).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25653156", "endSection": "abstract" }, { "offsetInBeginSection": 978, "offsetInEndSection": 1244, "text": "Together, our results animate recent DHX36 crystal structures, suggesting a model in which the DSM recruits G4s in a modular and flexible manner by contacting the 5' face early in binding, prior to rate-limiting capture and disruption of the G4 by the helicase core.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33857359", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 291, "text": "he DEAH helicase DHX37 (Dhr1 in yeast) is activated by the ribosome biogenesis factor UTP14A to facilitate maturation of the small ribosomal subunit. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30910870", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "DHX36 is a eukaryotic DEAH/RHA family helicase that disrupts G-quadruplex structures (G4s) with high specificity, contributing to regulatory roles of G4s.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33857359", "endSection": "abstract" }, { "offsetInBeginSection": 718, "offsetInEndSection": 944, "text": "DHX36\u00a0is a multi-functional helicase that has been implicated in G-quadruplex-mediated transcriptional and post-transcriptional regulation, and is essential for heart development, haematopoiesis, and embryogenesis in mice9-12.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29899445", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 717, "text": "DHX36 (also known as RHAU and G4R1), a member of the DEAH/RHA family of helicases, binds both DNA and RNA G-quadruplexes with extremely high affinity4-6, is consistently found bound to G-quadruplexes in cells7,8, and is a major source of G-quadruplex unfolding activity in HeLa cell lysates 6 .", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29899445", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 411, "text": "DEAH-Box helicase 36 (DHX36), a member of the large DExD/H box helicase family, enzymatically unwinds both G4 DNA and G4 RNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34862880", "endSection": "abstract" }, { "offsetInBeginSection": 200, "offsetInEndSection": 339, "text": "One example is DHX36, a DEAH-box helicase, which participates in gene expression and replication by recognizing and unwinding parallel G4s.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34025941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 129, "text": "The G-quadruplex (G4) resolvase DHX36 efficiently and specifically disrupts DNA G4s via a translocation-based helicase mechanism.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29269411", "endSection": "title" } ] }, { "body": "What is the function of the YY1 transcriptional regulator?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/9359867", "http://www.ncbi.nlm.nih.gov/pubmed/18046414", "http://www.ncbi.nlm.nih.gov/pubmed/24575094", "http://www.ncbi.nlm.nih.gov/pubmed/15955096", "http://www.ncbi.nlm.nih.gov/pubmed/26892542", "http://www.ncbi.nlm.nih.gov/pubmed/16314846", "http://www.ncbi.nlm.nih.gov/pubmed/26981420", "http://www.ncbi.nlm.nih.gov/pubmed/18542060", "http://www.ncbi.nlm.nih.gov/pubmed/22570637", "http://www.ncbi.nlm.nih.gov/pubmed/12411495", "http://www.ncbi.nlm.nih.gov/pubmed/9696045", "http://www.ncbi.nlm.nih.gov/pubmed/8276234", "http://www.ncbi.nlm.nih.gov/pubmed/16822951" ], "ideal_answer": [ "The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have a fundamental role in normal biologic processes such as embryogenesis, differentiation, replication, and cellular proliferation. YY1 is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes. YY1 overexpression and/or activation is associated with unchecked cellular proliferation, resistance to apoptotic stimuli, tumorigenesis and metastatic potential. YY1, in addition to its regulatory roles in normal biologic processes, may possess the potential to act as an initiator of tumorigenesis and may thus serve as both a diagnostic and prognostic tumor marker; furthermore, it may provide an effective target for antitumor chemotherapy and/or immunotherapy.", "The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have a fundamental role in normal biologic processes such as embryogenesis, differentiation, replication, and cellular proliferation. YY1 exerts its effects on genes involved in these processes via its ability to initiate, activate, or repress transcription depending upon the context in which it binds. Mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes.", "YY1 is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. We present evidence that YY1, a ubiquitously expressed DNA-binding protein, regulates the activity of the c-fos promoter primarily through an effect on DNA structure. the principal function of YY1 in this promoter is to bend DNA to regulate contact between other proteins. By using oligonucleotide competition and a specific antibody we demonstrated that the transcription factor YY1 is responsible for the formation of complex BIII. Also in this case, the transient expression of the YY1 cDNA in CHO cells resulted in an increased transcription from the FE65 minimal promoter. The absence of any co-operative effect when CHO cells were co-transfected with both YY1 and Pur alpha cDNA species suggests that two different transcription regulatory mechanisms could have a role in the regulation of the FE65 gene.", "YY1 is a transcriptional regulator. It is a protein that binds to the C-fos promoter. The function of this protein is to bend DNA to allow it to contact with other proteins." ], "type": "summary", "id": "5fd3c4f4a43ad31278000003", "snippets": [ { "offsetInBeginSection": 139, "offsetInEndSection": 306, "text": "We present evidence that YY1, a ubiquitously expressed DNA-binding protein, regulates the activity of the c-fos promoter primarily through an effect on DNA structure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8276234", "endSection": "abstract" }, { "offsetInBeginSection": 837, "offsetInEndSection": 943, "text": "the principal function of YY1 in this promoter is to bend DNA to regulate contact between other proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8276234", "endSection": "abstract" }, { "offsetInBeginSection": 1166, "offsetInEndSection": 1703, "text": "By using oligonucleotide competition and a specific antibody we demonstrated that the transcription factor YY1 is responsible for the formation of complex BIII. Also in this case, the transient expression of the YY1 cDNA in CHO cells resulted in an increased transcription from the FE65 minimal promoter. The absence of any co-operative effect when CHO cells were co-transfected with both YY1 and Pur alpha cDNA species suggests that two different transcription regulatory mechanisms could have a role in the regulation of the FE65 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9359867", "endSection": "abstract" }, { "offsetInBeginSection": 22, "offsetInEndSection": 129, "text": "c-Myc and the multifunctional transcriptional regulator YY1 have been shown previously to interact directly", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9696045", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 400, "text": "We demonstrate that YY1 is a potent inhibitor of c-Myc transforming activity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9696045", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 794, "text": "Furthermore the transactivation domain of YY1 was not necessary suggesting that gene regulation by YY1, for example through DNA bending or displacement of regulators from DNA, could be the cause for the negative regulation of c-Myc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9696045", "endSection": "abstract" }, { "offsetInBeginSection": 882, "offsetInEndSection": 1071, "text": "We suggest that the ability of RYBP to mediate an interaction between E2F2 or E2F3 and YY1 is an important component of Cdc6 activation and provides a basis for specificity of E2F function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12411495", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 757, "text": "In accordance with this result, when Sp1 or YY1 was overexpressed in keratinocytes, an obvious increase in ATP2C1 promoter activity was observed, which was in contrast with the case where a mutant promoter lacking the binding sites for Sp1 and YY1 was used as the reporter.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15955096", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1173, "text": "These results indicate that Sp1 and YY1 transactivate the human ATP2C1 promoter via cis-enhancing elements and that incomplete upregulation of ATP2C1 transcription contributes to the keratinocyte-specific pathogenesis of HHD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15955096", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have a fundamental role in normal biologic processes such as embryogenesis, differentiation, replication, and cellular proliferation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314846", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1265, "text": "YY1 overexpression and/or activation is associated with unchecked cellular proliferation, resistance to apoptotic stimuli, tumorigenesis and metastatic potential.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314846", "endSection": "abstract" }, { "offsetInBeginSection": 1775, "offsetInEndSection": 1906, "text": "recent findings implicate YY1 in the regulation of tumor cell resistance to chemotherapeutics and immune-mediated apoptotic stimuli", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314846", "endSection": "abstract" }, { "offsetInBeginSection": 1430, "offsetInEndSection": 1764, "text": "Molecular mechanisms that have been investigated include YY1-mediated downregulation of p53 activity, interference with poly-ADP-ribose polymerase, alteration in c-myc and nuclear factor-kappa B (NF-kappaB) expression, regulation of death genes and gene products, and differential YY1 binding in the presence of inflammatory mediators", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314846", "endSection": "abstract" }, { "offsetInBeginSection": 1985, "offsetInEndSection": 2287, "text": "YY1, in addition to its regulatory roles in normal biologic processes, may possess the potential to act as an initiator of tumorigenesis and may thus serve as both a diagnostic and prognostic tumor marker; furthermore, it may provide an effective target for antitumor chemotherapy and/or immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16314846", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "YY1 is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16822951", "endSection": "abstract" }, { "offsetInBeginSection": 996, "offsetInEndSection": 1167, "text": "Knockdown of YY1 caused a significant decrease in mitochondrial gene expression and in respiration, and YY1 was required for rapamycin-dependent repression of those genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18046414", "endSection": "abstract" }, { "offsetInBeginSection": 812, "offsetInEndSection": 1036, "text": "These and other results suggest that in quiescent cells the C-terminal region of p300 provides corepressor function and facilitates the recruitment of p300 and HDAC3 to the YY1-binding site and represses the c-Myc promoter. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18542060", "endSection": "abstract" }, { "offsetInBeginSection": 357, "offsetInEndSection": 523, "text": "Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22570637", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 727, "text": "Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22570637", "endSection": "abstract" }, { "offsetInBeginSection": 1105, "offsetInEndSection": 1160, "text": "Our recent data show that YY1 is also required for CSR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24575094", "endSection": "abstract" }, { "offsetInBeginSection": 1759, "offsetInEndSection": 1879, "text": "The large numbers of post-translational modifications that control YY1 functions are possible candidates for regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24575094", "endSection": "abstract" }, { "offsetInBeginSection": 66, "offsetInEndSection": 233, "text": "Here we describe the discovery and functional annotation of Linc-YY1, a novel lincRNA originating from the promoter of the transcription factor (TF) Yin Yang 1 (YY1). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26981420", "endSection": "abstract" }, { "offsetInBeginSection": 601, "offsetInEndSection": 679, "text": "YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26892542", "endSection": "abstract" } ] }, { "body": "Which CYP genes' expression is decreased at the in vivo level following pomegranate juice consumption?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18158835" ], "ideal_answer": [ "It was found that pomegranate juice consumption decreased total hepatic CYP content as well as the expression of CYP1A2 and CYP3A." ], "exact_answer": [ [ "CYP1A2" ], [ "CYP3A" ] ], "type": "list", "id": "620c01ae3a8413c653000005", "snippets": [ { "offsetInBeginSection": 859, "offsetInEndSection": 990, "text": "It was found that pomegranate juice consumption decreased total hepatic CYP content as well as the expression of CYP1A2 and CYP3A. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18158835", "endSection": "abstract" } ] }, { "body": "Class-defining mutations in which genes drive FLT3-ITD-mutant AML?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33956058" ], "ideal_answer": [ "Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA. These class-defining mutations frequently synergize with internal tandem duplications in FLT3 (FLT3-ITDs) to drive leukemogenesis.", "Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA.", "NPM1, MLL, and CEBPA", "NPM1, RUNX1, CEBPA, MLL" ], "exact_answer": [ [ "NPM1" ], [ "MLL" ], [ "CEBPA" ] ], "type": "list", "id": "62128a913a8413c653000017", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 336, "text": "Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA. These class-defining mutations frequently synergize with internal tandem duplications in FLT3 (FLT3-ITDs) to drive leukemogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33956058", "endSection": "abstract" } ] }, { "body": "Belzutifan has shown effectiveness for which diseases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34482771", "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "http://www.ncbi.nlm.nih.gov/pubmed/34818478", "http://www.ncbi.nlm.nih.gov/pubmed/33931436", "http://www.ncbi.nlm.nih.gov/pubmed/33945366", "http://www.ncbi.nlm.nih.gov/pubmed/34590859", "http://www.ncbi.nlm.nih.gov/pubmed/34479868" ], "ideal_answer": [ "Belzutifan is the small-molecule HIF 2 alpha inhibitor that has demonstrated significant efficacy in the von Hippel-Lindau disease related renal cell carcinomas, hemangioblastomas, and pancreatic neuroendocrine tumors while demonstrating an acceptable safety profile" ], "exact_answer": [ [ "renal cell carcinomas" ], [ "hemangioblastomas" ], [ "pancreatic neuroendocrine tumors" ] ], "type": "list", "id": "61f5924e882a024a1000000e", "snippets": [ { "offsetInBeginSection": 186, "offsetInEndSection": 692, "text": "AIM AND RESULTS: This article describes the main acquisitions of RCC management, including the advent of a new combo (pembrolizumab+lenvatinib) as first-line therapy, the confirmation of an OS advantage of ICI plus VEGFR-TKI combinations over sunitinib at longer follow-up, the persistent benefit from these combinations in particular subgroups (clear cell mRCC tumors with sarcomatoid differentiation), and possible new approaches in subsequent lines of therapy (including the HIF-2\u03b1 inhibitor belzutifan)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34482771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Belzutifan (Welireg\u2122) is an oral small molecule inhibitor of hypoxia-inducible factor (HIF)-2\u03b1 being developed by Peloton Therapeutics for the treatment of solid tumours, including renal cell carcinoma (RCC) with clear cell histology (ccRCC) and von Hippel-Lindau (VHL) disease-associated RCC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "A detailed mechanistic understanding of a benzylic photobromination en route to belzutifan (MK-6482, a small molecule for the treatment of renal cell carcinoma associated with von Hippel-Lindau syndrome) has been achieved using in situ LED-NMR spectroscopy in conjunction with kinetic analysis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590859", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34818478", "endSection": "title" }, { "offsetInBeginSection": 1752, "offsetInEndSection": 1966, "text": "CONCLUSIONS: Belzutifan was associated with predominantly grade 1 and 2 adverse events and showed activity in patients with renal cell carcinomas and non-renal cell carcinoma neoplasms associated with VHL disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34818478", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 872, "text": "The small-molecule HIF 2 alpha inhibitor MK-6482 (belzutifan) has demonstrated significant efficacy in VHL disease related renal cell carcinomas, hemangioblastomas, and pancreatic neuroendocrine tumors while demonstrating an acceptable safety profile.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33945366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "The HIF2\u03b1 Inhibitor Belzutifan Shows Signs of Efficacy in Kidney Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33931436", "endSection": "title" }, { "offsetInBeginSection": 256, "offsetInEndSection": 539, "text": "en-label, single-group trial, we investigated the efficacy and safety of the HIF-2\u03b1 inhibitor belzutifan (MK-6482, previously called PT2977), administered orally at a dose of 120 mg daily, in patients with renal cell carcinoma associated with VHL disease. The primary end point was o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34818478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 64, "text": "Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34818478", "endSection": "title" }, { "offsetInBeginSection": 608, "offsetInEndSection": 862, "text": "ifestations. The small-molecule HIF 2 alpha inhibitor MK-6482 (belzutifan) has demonstrated significant efficacy in VHL disease related renal cell carcinomas, hemangioblastomas, and pancreatic neuroendocrine tumors while demonstrating an acceptable safet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33945366", "endSection": "abstract" }, { "offsetInBeginSection": 306, "offsetInEndSection": 589, "text": "21, belzutifan received its first approval in the USA for the treatment of patients with VHL disease who require therapy for associated RCC, central nervous system (CNS) haemangioblastomas or pancreatic neuroendocrine tumours (pNET), not requiring immediate surgery. Clinical studies", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Belzutifan (Welireg\u2122) is an oral small molecule inhibitor of hypoxia-inducible factor (HIF)-2\u03b1 being developed by Peloton Therapeutics for the treatment of solid tumours, including renal cell carcinoma (RCC) with clear cell histology (ccRCC) and von Hippel-Lindau (VHL) disease-associated RCC. In August", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "endSection": "abstract" }, { "offsetInBeginSection": 592, "offsetInEndSection": 787, "text": " belzutifan (as monotherapy or combination therapy) in other indications, including ccRCC, pNET and phaeochromocytoma/paraganglioma, are also underway in various countries. This article summarize", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 1042, "text": "nifestations. The small-molecule HIF 2 alpha inhibitor MK-6482 (belzutifan) has demonstrated significant efficacy in VHL disease related renal cell carcinomas, hemangioblastomas, and pancreatic neuroendocrine tumors while demonstrating an acceptable safety profile.AREAS COVERED: This paper reviews the development of the HIF-2 alpha inhibitor, MK-6482, and discusses preliminary results of ongoing phase I/II studies in renal cell car", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33945366", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 293, "text": "Belzutifan (Welireg\u2122) is an oral small molecule inhibitor of hypoxia-inducible factor (HIF)-2\u03b1 being developed by Peloton Therapeutics for the treatment of solid tumours, including renal cell carcinoma (RCC) with clear cell histology (ccRCC) and von Hippel-Lindau (VHL) disease-associated RCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "endSection": "abstract" }, { "offsetInBeginSection": 573, "offsetInEndSection": 764, "text": "Clinical studies of belzutifan (as monotherapy or combination therapy) in other indications, including ccRCC, pNET and phaeochromocytoma/paraganglioma, are also underway in various countries.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "endSection": "abstract" }, { "offsetInBeginSection": 1423, "offsetInEndSection": 1922, "text": "tients) and fatigue (in 66%). Seven patients discontinued treatment: four patients voluntarily discontinued, one discontinued owing to a treatment-related adverse event (grade 1 dizziness), one discontinued because of disease progression as assessed by the investigator, and one patient died (of acute toxic effects of fentanyl).CONCLUSIONS: Belzutifan was associated with predominantly grade 1 and 2 adverse events and showed activity in patients with renal cell carcinomas and non-renal cell carci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34818478", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 572, "text": "In August 2021, belzutifan received its first approval in the USA for the treatment of patients with VHL disease who require therapy for associated RCC, central nervous system (CNS) haemangioblastomas or pancreatic neuroendocrine tumours (pNET), not requiring immediate surgery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34613603", "endSection": "abstract" } ] }, { "body": "Where are the PUX proteins found?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32601292", "http://www.ncbi.nlm.nih.gov/pubmed/34141135" ], "ideal_answer": [ "PUX proteins specifically associate with the nucleoskeleton underneath the INM." ], "exact_answer": [ "PUX proteins specifically associate with the nucleoskeleton underneath the INM." ], "type": "factoid", "id": "621b54f03a8413c65300003b", "snippets": [ { "offsetInBeginSection": 849, "offsetInEndSection": 1036, "text": " These PUX proteins specifically associate with the nucleoskeleton underneath the INM and physically interact with CDC48 proteins to negatively regulate INM protein degradation in plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32601292", "endSection": "abstract" }, { "offsetInBeginSection": 47, "offsetInEndSection": 83, "text": " plant UBX-containing (PUX) proteins", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34141135", "endSection": "title" }, { "offsetInBeginSection": 425, "offsetInEndSection": 813, "text": "The activity and targeting of CDC48 are controlled by adaptor proteins, of which the plant ubiquitin regulatory\u00a0X\u00a0(UBX) domain-containing (PUX) proteins constitute the largest family. Emerging knowledge on the structure and function of PUX proteins highlights that these proteins are versatile factors for plant homeostasis and adaptation that might inspire biotechnological applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34141135", "endSection": "abstract" } ] }, { "body": "Are Tregs CD4(+)CD25(+) regulatory T cells a positive regulator of the immune response?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/19816193", "http://www.ncbi.nlm.nih.gov/pubmed/18205702", "http://www.ncbi.nlm.nih.gov/pubmed/21386770", "http://www.ncbi.nlm.nih.gov/pubmed/17848162", "http://www.ncbi.nlm.nih.gov/pubmed/23531479", "http://www.ncbi.nlm.nih.gov/pubmed/17826781", "http://www.ncbi.nlm.nih.gov/pubmed/24095986", "http://www.ncbi.nlm.nih.gov/pubmed/16809644", "http://www.ncbi.nlm.nih.gov/pubmed/17368474", "http://www.ncbi.nlm.nih.gov/pubmed/23983771", "http://www.ncbi.nlm.nih.gov/pubmed/20843956", "http://www.ncbi.nlm.nih.gov/pubmed/17407195", "http://www.ncbi.nlm.nih.gov/pubmed/22749847", "http://www.ncbi.nlm.nih.gov/pubmed/34495808", "http://www.ncbi.nlm.nih.gov/pubmed/16020508", "http://www.ncbi.nlm.nih.gov/pubmed/18032693", "http://www.ncbi.nlm.nih.gov/pubmed/20384869", "http://www.ncbi.nlm.nih.gov/pubmed/23635849", "http://www.ncbi.nlm.nih.gov/pubmed/27109178", "http://www.ncbi.nlm.nih.gov/pubmed/18580479", "http://www.ncbi.nlm.nih.gov/pubmed/19005268", "http://www.ncbi.nlm.nih.gov/pubmed/24754976", "http://www.ncbi.nlm.nih.gov/pubmed/25113439", "http://www.ncbi.nlm.nih.gov/pubmed/19543397", "http://www.ncbi.nlm.nih.gov/pubmed/15778406", "http://www.ncbi.nlm.nih.gov/pubmed/16393984", "http://www.ncbi.nlm.nih.gov/pubmed/21597299", "http://www.ncbi.nlm.nih.gov/pubmed/17234458", "http://www.ncbi.nlm.nih.gov/pubmed/24483245", "http://www.ncbi.nlm.nih.gov/pubmed/21655351", "http://www.ncbi.nlm.nih.gov/pubmed/22899644" ], "ideal_answer": [ "CD4(+)CD25(+) regulatory T cells (Tregs) are negative regulators of the immune system that induce and maintain immune tolerance." ], "exact_answer": "no", "type": "yesno", "id": "621ed10f3a8413c653000062", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "The immunosuppressive effects of CD4+ CD25 high regulatory T cells (Tregs) interfere with antitumor immune responses in cancer patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19816193", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 146, "text": "Alteration of regulatory T cells (Tregs) may contribute to ineffective suppression of proinflammatory cytokines in type 1 diabetes.AIM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25113439", "endSection": "abstract" }, { "offsetInBeginSection": 110, "offsetInEndSection": 179, "text": "Regulatory T cells (Tregs) suppress excessive immune responses in IRI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24754976", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "CD4(+)CD25(+) regulatory T cells (Tregs) are negative regulators of the immune system that induce and maintain immune tolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24095986", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1022, "text": "lar to chronic patients, Treg from patients with PHI inhibited the proliferation of purified tuberculin (PPD) and HIV p24 activated CD4CD25 T cells. CD4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19005268", "endSection": "abstract" }, { "offsetInBeginSection": 655, "offsetInEndSection": 901, "text": " demonstrate that aTregs are necessary for tolerance, DBA/2 skin was transplanted onto C57BL/6-RAG-1-deficient recipients adoptively transferred with purified sorted CD4CD25 T cells; half of the recipients undergo tolerance induction treatment.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21386770", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "It is well established that CD4CD25 regulatory T cells (Tregs) downregulate inflammatory immune responses and help to maintain immune homeostasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23635849", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "In vitro expanded human CD4+CD25+ regulatory T cells are potent suppressors of T-cell-mediated xenogeneic responses.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18580479", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "BACKGROUND: Regulatory T cells (Tregs) are essential in the control of tolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19543397", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "CD4(+)CD25(+) regulatory T cells (Tregs) are critical for the peripheral immune tolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20384869", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 287, "text": "T regulatory cells (Tregs) have a role in immunosuppression and control of autoimmunity, and are currently an important topic in the study of immune response to tumor cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27109178", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "CD4+CD25+ regulatory T cells attenuate lipopolysaccharide-induced systemic inflammatory responses and promotes survival in murine Escherichia coli infection.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23635849", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "OBJECTIVES: CD4CD25 regulatory T cells (Tregs) play a key role in the prevention of various inflammatory and autoimmune disorders by suppressing immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23531479", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "CD25(High) CD4+ regulatory T cells (Treg cells) have been described as key players in immune regulation, preventing infection-induced immune pathology and limiting collateral tissue damage caused by vigorous anti-parasite immune response. In t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21655351", "endSection": "abstract" }, { "offsetInBeginSection": 240, "offsetInEndSection": 521, "text": "ic subset of T cells, currently recognized as FOXP3(+) CD25(+) CD4(+) regulatory T cells (Tregs), are pivotal in suppressing autoimmunity and maintaining immune homeostasis by mediating self-tolerance at the periphery as shown in autoimmune diseases and cancers. A growing body of ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22899644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "CD4+CD25+ regulatory T cells (Tregs) are essential negative regulators of immune responses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16020508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Accumulating evidence has demonstrated that naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are critical for maintenance of immunological tolerance and have been shown to be important in regulating the immune responses in many diseases. Curcu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22749847", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 426, "text": "4+CD25+ Foxp3+ regulatory T cells (Tregs) are recognized as one of the major regulatory factors in immune tolerance and inflammatory responses. Si", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24483245", "endSection": "abstract" }, { "offsetInBeginSection": 370, "offsetInEndSection": 552, "text": "lly occurring CD4(+)CD25(+) regulatory T cells (Tregs) have a key role in the prevention of various inflammatory and autoimmune disorders by suppressing immune responses. We tested t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17826781", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "CD4(+)CD25(+) regulatory T cells (Tregs) are considered to play a key role as suppressors of immune mediated reactions. The a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17368474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "CD4+ CD25+ T regulatory cells (Tregs) are classified as a subset of T cells whose role is the suppression and regulation of immune responses to self and non-self. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18205702", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "CD4(+)CD25(+) regulatory T cells (Tregs) are potent modulators of immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18032693", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "CD4+ T cells naturally expressing CD25 molecules (natural T regulatory cells (Tregs)) have a role in maintaining self tolerance and in regulating responses to infectious agents, transplantation Ags, and tumor Ags.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16393984", "endSection": "abstract" }, { "offsetInBeginSection": 157, "offsetInEndSection": 275, "text": "Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are essential for the active suppression of autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20843956", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 489, "text": "Amongst these, naturally occurring CD4(+)CD25(+) Treg cells (nTreg) represent a major lymphocyte population engaged in the dominant control of self-reactive T responses and maintaining tolerance in several models of autoimmunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16809644", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "CD4+CD25+ regulatory T cells (Tregs) are essential negative regulators of immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16020508", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells (CD25(+) Tregs) constitute a specialized population of T cells that is essential for the maintenance of peripheral self-tolerance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17407195", "endSection": "abstract" }, { "offsetInBeginSection": 68, "offsetInEndSection": 394, "text": "One of the subpopulations of CD4+ T cells that express CD25+ and the transcription factor FOXP3, known as Regulator T cells (TReg), plays an essential role in maintaining tolerance and immune homeostasis preventing autoimmune diseases, minimalize chronic inflammatory diseases by enlisting various immunoregulatory mechanisms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34495808", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 240, "text": "Regulatory T cells (Tregs) are CD4(+)CD25(bright)CD62L(high) cells that actively down-regulate immune responses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15778406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 202, "text": "CD4(+)CD25(+) regulatory T cells (Treg) play a central role in the prevention of autoimmunity and in the control of immune responses by down-regulating the function of effector CD4(+) or CD8(+) T cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17234458", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 389, "text": "FoxP3(+)CD25(+)CD4(+) regulatory T cells (Tregs) suppress a variety of normal physiological and pathological immune responses via several pathways, such as inhibitory cytokine secretion, direct cytolysis induction, and antigen-presenting cell functional modulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23983771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "Regulatory CD4(+) CD25(+) T (Treg) cells with the ability to suppress host immune responses against self- or non-self antigens play important roles in the processes of autoimmunity, transplant rejection, infectious diseases and cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17848162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: Evidence indicating that CD4+CD25+ regulatory T (Treg) cells play a crucial role in the maintenance of peripheral T cell tolerance to allergens has been ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21597299", "endSection": "abstract" } ] }, { "body": "Is Mediator present at super enhancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "http://www.ncbi.nlm.nih.gov/pubmed/27376235", "http://www.ncbi.nlm.nih.gov/pubmed/28839111", "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "http://www.ncbi.nlm.nih.gov/pubmed/23582323", "http://www.ncbi.nlm.nih.gov/pubmed/26416749", "http://www.ncbi.nlm.nih.gov/pubmed/25263550", "http://www.ncbi.nlm.nih.gov/pubmed/25955728", "http://www.ncbi.nlm.nih.gov/pubmed/28978570" ], "ideal_answer": [ "Yes. Super enhancers are clusters of enhancers that are densely occupied by the master regulator and mediator.", "Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers.", "Super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator.", "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes. Master transcription factors and mediator establish super-enhancers at key cell identity genes", "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes. Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs).", "Master transcription factors and mediator establish super-enhancers at key cell identity genes Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs).", "clusters of enhancers that are densely occupied by the master regulators", "Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator", "yes", "Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation." ], "exact_answer": "yes", "type": "yesno", "id": "5fdb4100a43ad31278000015", "snippets": [ { "offsetInBeginSection": 355, "offsetInEndSection": 449, "text": "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582323", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Master transcription factors and mediator establish super-enhancers at key cell identity genes", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "endSection": "abstract" }, { "offsetInBeginSection": 324, "offsetInEndSection": 466, "text": "These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23582322", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 840, "text": "BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25263550", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25547603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Mediator kinase inhibition further activates super-enhancer-associated genes in AML.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26416749", "endSection": "title" }, { "offsetInBeginSection": 839, "offsetInEndSection": 1048, "text": "Furthermore, the binding of SIM2 marks a particular sub-category of enhancers known as super-enhancers. These regions are characterized by typical DNA modifications and Mediator co-occupancy (MED1 and MED12). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25955728", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27376235", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "A number of studies have recently demonstrated that super-enhancers, which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28978570", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Super-enhancers are characterized by high levels of Mediator binding and are major contributors to the expression of their associated genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28839111", "endSection": "abstract" } ] }, { "body": "Does atemoya juice inhibit the CYP1A2 enzyme?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34881402" ], "ideal_answer": [ "Yes, atemoya juice inhibits the CYP1A2 enzyme." ], "exact_answer": "yes", "type": "yesno", "id": "62057b35c9dfcb9c0900002d", "snippets": [ { "offsetInBeginSection": 838, "offsetInEndSection": 962, "text": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881402", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1491, "text": "This suggests that the intake of an excess amount of atemoya juice is necessary to cause a change in the pharmacokinetics of phenacetin when the IC50 values for CYP1A2 inhibition by atemoya and fluvoxamine are taken into account", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34881402", "endSection": "abstract" } ] }, { "body": "What is caused by biallelic variants in SPATA5L1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34626583" ], "ideal_answer": [ "Biallelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss.", "Bi-allelic variants in SPATA5L1 lead to microcephaly, intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss." ], "exact_answer": [ [ "intellectual disability" ], [ "microcephaly" ], [ "spastic-dystonic cerebral palsy" ], [ "epilepsy" ], [ "hearing loss" ] ], "type": "list", "id": "620997e9c9dfcb9c09000042", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34626583", "endSection": "title" }, { "offsetInBeginSection": 113, "offsetInEndSection": 404, "text": "We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34626583", "endSection": "abstract" } ] }, { "body": "A combination of which two drugs was tested in the IMbrave150 trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33442538", "http://www.ncbi.nlm.nih.gov/pubmed/32349374", "http://www.ncbi.nlm.nih.gov/pubmed/34853653", "http://www.ncbi.nlm.nih.gov/pubmed/34798793", "http://www.ncbi.nlm.nih.gov/pubmed/33663220", "http://www.ncbi.nlm.nih.gov/pubmed/34522691", "http://www.ncbi.nlm.nih.gov/pubmed/33139264", "http://www.ncbi.nlm.nih.gov/pubmed/34051880", "http://www.ncbi.nlm.nih.gov/pubmed/33549983", "http://www.ncbi.nlm.nih.gov/pubmed/34771637", "http://www.ncbi.nlm.nih.gov/pubmed/32984090", "http://www.ncbi.nlm.nih.gov/pubmed/33213161", "http://www.ncbi.nlm.nih.gov/pubmed/34377156", "http://www.ncbi.nlm.nih.gov/pubmed/34167423", "http://www.ncbi.nlm.nih.gov/pubmed/34189869", "http://www.ncbi.nlm.nih.gov/pubmed/34245216" ], "ideal_answer": [ "IMbrave150 trial tested a combination of atezolizumab and bevacizumab for advanced hepatocellular carcinoma." ], "exact_answer": [ [ "atezolizumab" ], [ "bevacizumab" ] ], "type": "list", "id": "602346eb1cb411341a000090", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "A successful phase III trial for the combination of atezolizumab and bevacizumab (the IMbrave150 trial) in advanced hepatocellular carcinoma has recently been reported. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32349374", "endSection": "abstract" }, { "offsetInBeginSection": 1120, "offsetInEndSection": 1460, "text": "ndeed, preliminary results from phase I studies of lenvatinib plus pembrolizumab and atezolizumab plus bevacizumab have proved favorable, prompting phase III investigations in the frontline setting, and for atezolizumab plus bevacizumab, these positive findings have been substantiated by recent reporting of phase III data from IMbrave150.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32984090", "endSection": "abstract" }, { "offsetInBeginSection": 238, "offsetInEndSection": 421, "text": "The approval was based on data from Study IMbrave150, which randomly allocated (2:1) patients to receive either atezolizumab plus bevacizumab (atezolizumab-bevacizumab) or sorafenib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33139264", "endSection": "abstract" }, { "offsetInBeginSection": 1993, "offsetInEndSection": 2134, "text": "In study IMbrave150, the combination of atezolizumab and bevacizumab was successfully used compared to sorafenib in the first-line treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33213161", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 261, "text": "The IMbrave150 trial set atezolizumab-bevacizumab as a new standard-of-care first-line treatment for unresectable HCC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34798793", "endSection": "abstract" }, { "offsetInBeginSection": 1107, "offsetInEndSection": 1382, "text": "A recent phase III trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33442538", "endSection": "abstract" }, { "offsetInBeginSection": 852, "offsetInEndSection": 1188, "text": "However, in 2020, the IMbrave150 trial demonstrated that combination therapy of atezolizumab (anti-programmed death-ligand 1 [PD-L1]) and bevacizumab (anti-vascular endothelial growth factor [VEGF]) is superior to sorafenib, a single anti-programmed death 1/PD-L1 antibody inhibitor used as an anti-cancer monotherapy for HCC treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34853653", "endSection": "abstract" }, { "offsetInBeginSection": 684, "offsetInEndSection": 857, "text": "The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34522691", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 879, "text": "nt Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34522691", "endSection": "abstract" }, { "offsetInBeginSection": 279, "offsetInEndSection": 498, "text": "ation treatment with atezolizumab (targeting PD-L1) and bevacizumab (targeting VEGF) in the recent IMbrave150 study was shown to be effective with an acceptable safety profile in patients with unresectable HCC. Herein, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33663220", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34377156", "endSection": "abstract" }, { "offsetInBeginSection": 736, "offsetInEndSection": 1011, "text": "he IMbrave150 trial recently showed that, among patients with previously untreated unresectable HCC, treatment with atezolizumab plus bevacizumab resulted in significantly longer overall survival and progression-free survival compared to sorafenib monotherapy. In addition, t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33549983", "endSection": "abstract" }, { "offsetInBeginSection": 350, "offsetInEndSection": 625, "text": "e 3 IMbrave150 clinical trial was successful because of the direct antitumor effect of bevacizumab, which shifted the suppressive immune microenvironment to a responsive immune microenvironment, in addition to its synergistic effects when combined with atezolizumab. The anal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34771637", "endSection": "abstract" }, { "offsetInBeginSection": 1124, "offsetInEndSection": 1401, "text": "I trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon. This review descri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33442538", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 233, "text": "BACKGROUND: IMbrave150 is a phase III trial that assessed atezolizumab\u00a0+\u00a0bevacizumab (ATEZO/BEV) versus sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (HCC) and demonstrated a significant improvement in clinic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34189869", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "A successful phase III trial for the combination of atezolizumab and bevacizumab (the IMbrave150 trial) in advanced hepatocellular carcinoma has recently been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32349374", "endSection": "abstract" }, { "offsetInBeginSection": 69, "offsetInEndSection": 488, "text": " important. We aimed to evaluate patient-reported outcomes (PROs) with atezolizumab plus bevacizumab versus sorafenib in patients with advanced hepatocellular carcinoma in the IMbrave150 trial, which has already shown significant overall survival and progression-free survival benefits with this combination therapy.METHODS: We did an open-label, randomised, phase 3 trial in 111 hospitals and cancer centres across 17 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34051880", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "AIM: A clinical trial (IMbrave150) indicated the efficacy and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34245216", "endSection": "abstract" }, { "offsetInBeginSection": 342, "offsetInEndSection": 616, "text": "The phase 3 IMbrave150 clinical trial was successful because of the direct antitumor effect of bevacizumab, which shifted the suppressive immune microenvironment to a responsive immune microenvironment, in addition to its synergistic effects when combined with atezolizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34771637", "endSection": "abstract" }, { "offsetInBeginSection": 160, "offsetInEndSection": 469, "text": "CC). In this study, we evaluated this therapeutic combination in a real-world setting, with a focus on patients who did not meet the IMbrave150 eligibility criteria.METHODS: In this multicenter study, patients with unresectable HCC treated with atezolizumab plus bevacizumab between October 2020 and May 2021 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34245216", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 774, "text": "The efficacy of the combination was first assessed in the phase Ib GO30140 study, and the combination was then proven superior to the prior standard of care, sorafenib, in the phase III IMbrave150 trial.Areas covered: This article focuses on the mechanism of action of atezolizumab and bevacizumab, their synergistic action, and the two clinical trials leading to approval.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34167423", "endSection": "abstract" }, { "offsetInBeginSection": 273, "offsetInEndSection": 489, "text": "Combination treatment with atezolizumab (targeting PD-L1) and bevacizumab (targeting VEGF) in the recent IMbrave150 study was shown to be effective with an acceptable safety profile in patients with unresectable HCC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33663220", "endSection": "abstract" } ] }, { "body": "Is ALS a heritable disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31959876", "http://www.ncbi.nlm.nih.gov/pubmed/33027627", "http://www.ncbi.nlm.nih.gov/pubmed/34025336", "http://www.ncbi.nlm.nih.gov/pubmed/34587215", "http://www.ncbi.nlm.nih.gov/pubmed/32391572" ], "ideal_answer": [ "Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance." ], "type": "summary", "id": "6217dba43a8413c653000029", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 427, "text": "Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disorder. The disease is characterized by degeneration of upper and lower motor neurons, leading to death usually within five years after the onset of symptoms. While most cases are sporadic, 5%-10% of cases can be associated with familial inheritance, including ALS type 6, which is associated with mutations in the Fused in Sarcoma (FUS) gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34587215", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33027627", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "Amyotrophic lateral sclerosis (ALS) is a severe disease causing motor neuron death, but a complete cure has not been developed and related genes have not been defined in more than 80% of cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31959876", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. The majority of cases are sporadic (sALS), while the most common inherited form is due to C9orf72 mutation (C9ALS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32391572", "endSection": "abstract" }, { "offsetInBeginSection": 181, "offsetInEndSection": 268, "text": "At least 30 genes have been implicated in familial ALS (fALS) and sporadic ALS (sALS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34025336", "endSection": "abstract" } ] }, { "body": "What is ARNIL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28251886" ], "ideal_answer": [ "Long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) is involved in several human cancers." ], "type": "summary", "id": "62211fdf3a8413c653000073", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) is involved in several human cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28251886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) is involved in several human cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28251886", "endSection": "abstract" } ] }, { "body": "What is the indication of CPX-351?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34256819" ], "ideal_answer": [ "CPX-351 has been approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes." ], "type": "summary", "id": "6211575f3a8413c653000011", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 362, "text": "CPX-351 (United States: Vyxeos\u00ae; Europe: Vyxeos\u00ae Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34256819", "endSection": "abstract" } ] }, { "body": "List signs of patients with biallelic variants in KARS1", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34172899" ], "ideal_answer": [ "KARS1-associated signs are autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement.", "Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated in the knockout zebrafish." ], "exact_answer": [ [ "autism" ], [ "hyperactive behavior" ], [ "pontine hypoplasia" ], [ "cerebellar atrophy with prevalent vermian involvement" ] ], "type": "list", "id": "61f808cd882a024a1000003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34172899", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 1217, "text": "Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo.METHODS: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic\u00a0in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish.RESULTS: We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34172899", "endSection": "abstract" } ] }, { "body": "Which substance use is associated with Brodifacoum poisoning?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31579608", "http://www.ncbi.nlm.nih.gov/pubmed/32659068", "http://www.ncbi.nlm.nih.gov/pubmed/32300441", "http://www.ncbi.nlm.nih.gov/pubmed/32771937", "http://www.ncbi.nlm.nih.gov/pubmed/9111096", "http://www.ncbi.nlm.nih.gov/pubmed/33132381", "http://www.ncbi.nlm.nih.gov/pubmed/30280655", "http://www.ncbi.nlm.nih.gov/pubmed/30022308" ], "ideal_answer": [ "Brodifacoum poisoning was linked to marijuana use." ], "exact_answer": [ "marijuana" ], "type": "factoid", "id": "6024a6871cb411341a0000a4", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Brodifacoum Poisoning Linked to Synthetic Marijuana Use in Wisconsin.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32659068", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 516, "text": "INTRODUCTION: Recent outbreaks of brodifacoum-induced coagulopathy resulting from the use of synthetic cannabinoids represents a growing public health concern. Brodifacoum is a commonly used and commercially available rodenticide that has anticoagulant properties. As new, unregulated synthetic cannabinoids enter the market, the potential for further outbreaks continues to rise.CASE PRESENTATION: We report a case of severe bleeding secondary to inhalation of synthetic cannabinoids contaminated with brodifacoum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32659068", "endSection": "abstract" }, { "offsetInBeginSection": 933, "offsetInEndSection": 1171, "text": "CONCLUSION: While hemorrhaging after exposure to synthetic cannabinoids has been reported previously, we use this case to increase awareness of the potentially deadly exposures to brodifacoum from synthetic cannabinoids use in Wisconsin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32659068", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Disseminated Intravascular Coagulopathy Secondary to Unintentional Brodifacoum Poisoning via Synthetic Marijuana.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32300441", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Recent evidence demonstrates a rising epidemic of unintentional brodifacoum poisoning associated with synthetic cannabinoid use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32300441", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 387, "text": "We present a rare case of severe coagulopathy and cardiac arrest secondary to synthetic cannabinoid use complicated by brodifacoum toxicity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32300441", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "Brodifacoum Poisoning Linked to Synthetic Marijuana Use in Wisconsin", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32659068", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Recent evidence demonstrates a rising epidemic of unintentional brodifacoum poisoning associated with synthetic cannabinoid use", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32300441", "endSection": "abstract" }, { "offsetInBeginSection": 127, "offsetInEndSection": 391, "text": "ently, brodifacoum-contaminated synthetic marijuana has led to multiple deaths and morbidity throughout the USA from severe coagulopathy associated with use of this strain of the drug (brodifacoum is a rodenticide and potent Vitamin K antagonist/anticoagulant). We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30022308", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Brodifacoum-contaminated synthetic marijuana: clinical and radiologic manifestations of a public health outbreak causing life-threatening coagulopathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30022308", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "INTRODUCTION: Recent outbreaks of brodifacoum-induced coagulopathy resulting from the use of synthetic cannabinoids represents a growing public h", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32659068", "endSection": "abstract" }, { "offsetInBeginSection": 1215, "offsetInEndSection": 1368, "text": "CONCLUSIONS Brodifacoum-laced synthetic marijuana toxicity can lead to potentially lethal complications if not recognized and treated in a timely manner.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33132381", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Brodifacoum intoxication with marijuana smoking.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9111096", "endSection": "title" }, { "offsetInBeginSection": 983, "offsetInEndSection": 1222, "text": "Brodifacoum use is authorized as rodenticide in many countries worldwide, but has been reported as cause of severe coagulopathies in humans, both intentional or involuntary, even consumed as a contaminant of herbal drugs, such as cannabis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32771937", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "We report the case of a 17-year-old boy with a significant history of drug and alcohol abuse, which included smoking marijuana mixed with brodifacoum.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9111096", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 385, "text": "se effects. There have been sporadic reports of co-consumption of illicit drugs with rodenticides such as warfarin and brodifacoum (BFC) over the past 20 years but recently, hundreds of people have been reported to have been poisoned with a mixture of synthetic cannabino", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31579608", "endSection": "abstract" }, { "offsetInBeginSection": 124, "offsetInEndSection": 388, "text": "Recently, brodifacoum-contaminated synthetic marijuana has led to multiple deaths and morbidity throughout the USA from severe coagulopathy associated with use of this strain of the drug (brodifacoum is a rodenticide and potent Vitamin K antagonist/anticoagulant).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30022308", "endSection": "abstract" }, { "offsetInBeginSection": 251, "offsetInEndSection": 660, "text": "binoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.METHODS: We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid-ass", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30280655", "endSection": "abstract" } ] }, { "body": "What is Alphafold?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34469019", "http://www.ncbi.nlm.nih.gov/pubmed/34265844", "http://www.ncbi.nlm.nih.gov/pubmed/34586808" ], "ideal_answer": [ "AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm." ], "exact_answer": [ "Highly accurate protein structure prediction approoach" ], "type": "factoid", "id": "621b4a223a8413c65300003a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "Highly accurate protein structure prediction with AlphaFold.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34265844", "endSection": "title" }, { "offsetInBeginSection": 1469, "offsetInEndSection": 1678, "text": "AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34265844", "endSection": "abstract" }, { "offsetInBeginSection": 93, "offsetInEndSection": 218, "text": "Using novel deep learning, AF2 predicted the structures of many difficult protein targets at or near experimental resolution.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34586808", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 324, "text": " Using the neural network-based method AlphaFold2, 3D structures of almost the entire human proteome have been predicted and made available (https://www.alphafold.ebi.ac.uk).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34469019", "endSection": "abstract" } ] }, { "body": "List diseases that are repeat expansion disorders (REDs).", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34054431", "http://www.ncbi.nlm.nih.gov/pubmed/14526165", "http://www.ncbi.nlm.nih.gov/pubmed/25886163", "http://www.ncbi.nlm.nih.gov/pubmed/34502075", "http://www.ncbi.nlm.nih.gov/pubmed/19710035", "http://www.ncbi.nlm.nih.gov/pubmed/8908515", "http://www.ncbi.nlm.nih.gov/pubmed/26420841", "http://www.ncbi.nlm.nih.gov/pubmed/25726753", "http://www.ncbi.nlm.nih.gov/pubmed/29325606", "http://www.ncbi.nlm.nih.gov/pubmed/32695777", "http://www.ncbi.nlm.nih.gov/pubmed/10766906", "http://www.ncbi.nlm.nih.gov/pubmed/8900536", "http://www.ncbi.nlm.nih.gov/pubmed/32619224", "http://www.ncbi.nlm.nih.gov/pubmed/32589669", "http://www.ncbi.nlm.nih.gov/pubmed/9302257" ], "ideal_answer": [ "The expansion of Short tandem repeats underlies the pathogenesis of multiple neurological disorders, including Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, fragile X-associated tremor/ataxia syndrome, and myotonic dystrophies, known as repeat expansion disorders (REDs).", "he Fragile-X related disorders (FXDs) are Repeat Expansion Diseases (REDs) that result from expansion of a CGG-repeat tract located at the 5' end of the FMR1 gene." ], "exact_answer": [ [ "Huntington's disease," ], [ "amyotrophic lateral sclerosis" ], [ "frontotemporal dementia" ], [ "fragile X-associated tremor/ataxia syndrome", "FRAXA", "FRAXE" ], [ "myotonic dystrophies" ], [ "FMR1 disorders,", "Fragile X-related disorders (FXDs)," ], [ "SCA3 (Spinocerebellar ataxia Type 3 or Machado-Joseph disease)" ], [ "DRPLA (Dentatorubropallidoluysian atrophy)" ], [ "SBMA (Spinal and bulbar muscular atrophy" ], [ "Baratela-Scott syndrome" ] ], "type": "list", "id": "621fc8513a8413c653000063", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Fragile X-related disorders (FXDs), also known as FMR1 disorders, are examples of repeat expansion diseases (REDs), clinical conditions that arise from an increase in the number of repeats in a disease-specific microsatellite. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34502075", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 165, "text": "he Fragile-X related disorders (FXDs) are Repeat Expansion Diseases (REDs) that result from expansion of a CGG-repeat tract located at the 5' end of the FMR1 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32695777", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 446, "text": "An increased polyglutamine chain size leads to a more severe disease, thus correlating with the genetic anticipation seen in repeat expansion disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8908515", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Expanded CAG repeat sequences have been identified in the coding region of genes mutated in several neurodegenerative disorders, including spinocerebellar ataxia type 1 and Machado-Joseph disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8908515", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 276, "text": "Among these is Machado-Joseph disease, one of the most common spinocerebellar ataxias (MJD/SCA3), caused by a CAG repeat expansion on chromosome 14.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8900536", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Absence of unidentified CAG repeat expansion in patients with Huntington's disease-like phenotype.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10766906", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "Fragile X-related disorders (FXDs), also known as FMR1 disorders, are examples of repeat expansion diseases (REDs), clinical conditions that arise from an increase in the number of repeats in a disease-specific microsatellite. In the case of FXDs, the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34502075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "The Fragile-X related disorders (FXDs) are Repeat Expansion Diseases (REDs) that result from expansion of a CGG-repeat tract located at the 5' end of the FMR1 gene. While expansion affects t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32695777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Fragile X-associated disorders are Repeat Expansion Diseases that result from expansion of a CGG/CCG-repeat in the FMR1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26420841", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The Fragile X-related disorders (FXDs) are members of the Repeat Expansion Diseases, a group of human genetic conditions resulting from expansion of a specific tandem repeat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25886163", "endSection": "abstract" }, { "offsetInBeginSection": 464, "offsetInEndSection": 894, "text": "Repeat expansion diseases include both causes of myotonic dystrophy (DM1 and DM2), the most common genetic cause of amyotrophic lateral sclerosis/frontotemporal dementia (C9ORF72), Huntington disease, and eight other polyglutamine disorders, including the most common forms of dominantly inherited ataxia, the most common recessive ataxia (Friedreich ataxia), and the most common heritable mental retardation (fragile X syndrome).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29325606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "The Fragile-X related disorders (FXDs) are Repeat Expansion Diseases (REDs) that result from expansion of a CGG-repeat tract located at the 5' end of the FMR1 ge", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32695777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 224, "text": "Fragile X-related disorders (FXDs), also known as FMR1 disorders, are examples of repeat expansion diseases (REDs), clinical conditions that arise from an increase in the number of repeats in a disease-specific microsatellit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34502075", "endSection": "abstract" }, { "offsetInBeginSection": 546, "offsetInEndSection": 757, "text": "epeat expansion-associated diseases, fragile X-associated tremor/ataxia syndrome (FXTAS), is caused by a CGG repeat expansion in the 5'UTR region of the fragile X mental retardation 1 (FMR1) gene. Moreover, rece", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34054431", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene causes the fragile X-related disorders (FXDs; aka the FMR1 disorders).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589669", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "The fragile X-related disorders (FXDs) are members of the group of diseases known as the repeat expansion diseases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25726753", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "Expansion of a tandem repeat tract is responsible for the Repeat Expansion diseases, a group of more than 20 human genetic disorders that includes those like Fragile X (FX) syndrome that result from repeat expansion in the FMR1 gene. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19710035", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "Fragile X-related disorders (FXDs), also known as FMR1 disorders, are examples of repeat expansion diseases (REDs), clinical conditions that arise from an increase in the number of repeats in a disease-specific microsatellite.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34502075", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "The Fragile-X related disorders (FXDs) are Repeat Expansion Diseases (REDs) that result from expansion of a CGG-repeat tract located at the 5' end of the FMR1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32695777", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "CAG repeat expansions have been identified as the disease-causing dynamic mutations in the coding regions of genes in several dominantly inherited neurodegenerative disorders, including spinobulbar muscular atrophy, Huntington's disease, dentatorubral-pallidoluysian atrophy, spinocerebellar ataxia type 1, 2 and 6 and Machado-Joseph disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9302257", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "The Fragile X-related disorders (FXDs) are Repeat Expansion Diseases, genetic disorders that result from the expansion of a disease-specific microsatellite.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32619224", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Fragile X mental retardation syndrome, FRAXE mental retardation, Progressive myoclonus epilepsy Type I, and Friedreich ataxia are members of a larger group of genetic disorders known as the Repeat Expansion Diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14526165", "endSection": "abstract" } ] }, { "body": "What is bb21217?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34256819", "http://www.ncbi.nlm.nih.gov/pubmed/32055000" ], "ideal_answer": [ "BB21217 is a chimeric antigen receptor (CAR)-modified T-cell therapy used to target B-cell maturation antigen (BCMA) in the treatment of multiple myeloma." ], "type": "summary", "id": "621150333a8413c65300000e", "snippets": [ { "offsetInBeginSection": 1074, "offsetInEndSection": 1584, "text": "Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy. We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE\u00ae (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody-drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32055000", "endSection": "abstract" } ] }, { "body": "Describe the syndrome that is caused by biallelic variants in HPDL", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33970200" ], "ideal_answer": [ "Biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays." ], "type": "summary", "id": "61f81785882a024a1000003f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33970200", "endSection": "title" }, { "offsetInBeginSection": 1424, "offsetInEndSection": 1637, "text": "Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33970200", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33970200", "endSection": "title" } ] }, { "body": "Which receptor is targeted by Spesolimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33919434", "http://www.ncbi.nlm.nih.gov/pubmed/34626330", "http://www.ncbi.nlm.nih.gov/pubmed/34678325", "http://www.ncbi.nlm.nih.gov/pubmed/33661508", "http://www.ncbi.nlm.nih.gov/pubmed/33785490", "http://www.ncbi.nlm.nih.gov/pubmed/34085329", "http://www.ncbi.nlm.nih.gov/pubmed/32884319" ], "ideal_answer": [ "Spesolimab is a novel anti-interleukin-36 receptor antibody." ], "exact_answer": [ "interleukin-36" ], "type": "factoid", "id": "61f5847b882a024a10000008", "snippets": [ { "offsetInBeginSection": 536, "offsetInEndSection": 771, "text": "A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33785490", "endSection": "abstract" }, { "offsetInBeginSection": 226, "offsetInEndSection": 379, "text": "The objectives of this study were to evaluate the safety and efficacy of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients with PPP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33661508", "endSection": "abstract" }, { "offsetInBeginSection": 1049, "offsetInEndSection": 1235, "text": "Directing treatment at neutrophil recruitment and activation by targeting IL-36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34085329", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 485, "text": "Two IL-36R blocking antibodies, imsidolimab and spesolimab, are currently undergoing phase II and III clinical trials, with promising results.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33919434", "endSection": "abstract" }, { "offsetInBeginSection": 107, "offsetInEndSection": 291, "text": " In a proof-of-concept clinical trial, treatment with spesolimab, an anti-IL-36 receptor antibody, resulted in rapid skin and pustular clearance in patients presenting with GPP flares.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34678325", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1858, "text": "Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34626330", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Spesolimab, an Anti-Interleukin-36 Receptor Antibody, in Patients with Palmoplantar Pustulosis: Results of a Phase IIa, Multicenter, Double-Blind, Randomized, Placebo-Controlled Pilot Study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33661508", "endSection": "title" }, { "offsetInBeginSection": 108, "offsetInEndSection": 291, "text": "In a proof-of-concept clinical trial, treatment with spesolimab, an anti-IL-36 receptor antibody, resulted in rapid skin and pustular clearance in patients presenting with GPP flares.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34678325", "endSection": "abstract" }, { "offsetInBeginSection": 1388, "offsetInEndSection": 1619, "text": "Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32884319", "endSection": "abstract" }, { "offsetInBeginSection": 1679, "offsetInEndSection": 1857, "text": "Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34626330", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 373, "text": "h PPP. The objectives of this study were to evaluate the safety and efficacy of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients wit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33661508", "endSection": "abstract" }, { "offsetInBeginSection": 1720, "offsetInEndSection": 1900, "text": "6 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. The emerging drugs for pustular psoriasis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34626330", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 766, "text": "ares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP f", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33785490", "endSection": "abstract" }, { "offsetInBeginSection": 1415, "offsetInEndSection": 1647, "text": "IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32884319", "endSection": "abstract" }, { "offsetInBeginSection": 1065, "offsetInEndSection": 1250, "text": "ent at neutrophil recruitment and activation by targeting IL-36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending. In contrast to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34085329", "endSection": "abstract" }, { "offsetInBeginSection": 98, "offsetInEndSection": 283, "text": "is (GPP). In a proof-of-concept clinical trial, treatment with spesolimab, an anti-IL-36 receptor antibody, resulted in rapid skin and pustular clearance in patients presenting with GPP", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34678325", "endSection": "abstract" }, { "offsetInBeginSection": 96, "offsetInEndSection": 706, "text": "asis (GPP). In a proof-of-concept clinical trial, treatment with spesolimab, an anti-IL-36 receptor antibody, resulted in rapid skin and pustular clearance in patients presenting with GPP flares.OBJECTIVE: We sought to compare the molecular profiles of lesional and nonlesional skin from patients with GPP or palmoplantar pustulosis (PPP) with skin from healthy volunteers, and to investigate the molecular changes after spesolimab treatment in the skin and blood of patients with GPP flares.METHODS: Pre- and post-treatment skin and blood samples were collected from patients with GPP who participated in a si", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34678325", "endSection": "abstract" } ] }, { "body": "Is NfL (neurofilament light chain) a biomarker of neurodegeneration?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34375485", "http://www.ncbi.nlm.nih.gov/pubmed/32306372", "http://www.ncbi.nlm.nih.gov/pubmed/34519102", "http://www.ncbi.nlm.nih.gov/pubmed/34556565", "http://www.ncbi.nlm.nih.gov/pubmed/34480363" ], "ideal_answer": [ "Yes,\nNeurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD)." ], "exact_answer": "yes", "type": "yesno", "id": "6217dc9d3a8413c65300002d", "snippets": [ { "offsetInBeginSection": 24, "offsetInEndSection": 142, "text": "Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34375485", "endSection": "abstract" }, { "offsetInBeginSection": 227, "offsetInEndSection": 360, "text": "Neurofilament light chain (NfL) is a new, non-disease specific, widely studied biomarker indicative of axonal injury and degeneration", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32306372", "endSection": "abstract" }, { "offsetInBeginSection": 709, "offsetInEndSection": 773, "text": "the neurodegeneration biomarker neurofilament light chain (NfL) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34556565", "endSection": "abstract" }, { "offsetInBeginSection": 1408, "offsetInEndSection": 1520, "text": "bNfL can be used as a potential biomarker to predict disease onset, severity, and progression of genetic ataxia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34519102", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 98, "text": "Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34480363", "endSection": "abstract" } ] }, { "body": "Is Epistaxis associated with dental implant placement?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24155599", "http://www.ncbi.nlm.nih.gov/pubmed/30719578" ], "ideal_answer": [ "Epistaxis is a frequent complication associated with dental implant placement." ], "exact_answer": "yes", "type": "yesno", "id": "621ebec63a8413c65300005d", "snippets": [ { "offsetInBeginSection": 2399, "offsetInEndSection": 2683, "text": " The overall survival rate of the implants into the sinus cavity was 95.6%, without statistical differences according to the level of penetration. The clinical and radiological complications were 3.4% and 14.8% respectively. The most frequent clinical complication was the epistaxis, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30719578", "endSection": "abstract" }, { "offsetInBeginSection": 1075, "offsetInEndSection": 1352, "text": "implant placement and protrusion of the implant up to 3mm beyond the sinus floor does not alter the stability and outcome of dental implants, one year post-restoration. This could be associated with minor complications ranging from epistaxis to sinusitis, which are manageable.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24155599", "endSection": "abstract" } ] }, { "body": "What is the effect of grapefruit juice on CYP3A4?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31828807" ], "ideal_answer": [ "Grapefruit juice inhibits CYP3A4 activity." ], "exact_answer": [ "Inhibitory" ], "type": "factoid", "id": "62058198c9dfcb9c09000030", "snippets": [ { "offsetInBeginSection": 886, "offsetInEndSection": 995, "text": "The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with \u03b3CD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31828807", "endSection": "abstract" }, { "offsetInBeginSection": 1175, "offsetInEndSection": 1389, "text": "The encapsulation of BG and DHBG by \u03b3CD and the resulting attenuation of the inhibition of CYP3A activity by grapefruit juice may be applicable to juice processing for preventing drug-grapefruit juice interactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31828807", "endSection": "abstract" } ] }, { "body": "Which is the major clinical feature observed in FDXR-associated disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33938912" ], "ideal_answer": [ "FDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort.", "Retinal dystrophy is a major clinical feature observed in FDXR-associated disease." ], "exact_answer": [ "Retinal dystrophy" ], "type": "factoid", "id": "61f81857882a024a10000040", "snippets": [ { "offsetInBeginSection": 1204, "offsetInEndSection": 1531, "text": "FDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort. In addition, we hypothesize that a number of factors are likely to drive the pathogenesis of optic atrophy, retinal degeneration, and perhaps the associated systemic manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33938912", "endSection": "abstract" } ] }, { "body": "Is Daprodustat effective for anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33744933", "http://www.ncbi.nlm.nih.gov/pubmed/33597868", "http://www.ncbi.nlm.nih.gov/pubmed/31306555", "http://www.ncbi.nlm.nih.gov/pubmed/34739194", "http://www.ncbi.nlm.nih.gov/pubmed/34713596", "http://www.ncbi.nlm.nih.gov/pubmed/27978511", "http://www.ncbi.nlm.nih.gov/pubmed/32250021", "http://www.ncbi.nlm.nih.gov/pubmed/34739196", "http://www.ncbi.nlm.nih.gov/pubmed/33628028", "http://www.ncbi.nlm.nih.gov/pubmed/31640478", "http://www.ncbi.nlm.nih.gov/pubmed/33964183", "http://www.ncbi.nlm.nih.gov/pubmed/33561857" ], "ideal_answer": [ "Yes. Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease." ], "exact_answer": "yes", "type": "yesno", "id": "61f58a1a882a024a10000009", "snippets": [ { "offsetInBeginSection": 1989, "offsetInEndSection": 2122, "text": "CONCLUSIONS: Oral daprodustat was noninferior to CERA in achieving and maintaining target hemoglobin levels in Japanese ND patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33561857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 346, "text": "BACKGROUND: The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is non-inferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: haemoglobin efficacy and cardiovascular safety.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33744933", "endSection": "abstract" }, { "offsetInBeginSection": 397, "offsetInEndSection": 749, "text": "Daprodustat is one of the orally administrated small-molecule HIF-PH inhibitors, leading to an increase in erythropoietin production, which is regulated by HIF. Also, daprodustat is expected to improve iron metabolism. Recently, several clinical trials showed its efficacy and safety in both hemodialysis- and non-hemodialysis- dependent CKD patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33628028", "endSection": "abstract" }, { "offsetInBeginSection": 819, "offsetInEndSection": 1003, "text": "Once-daily oral daprodustat treatment was generally well tolerated and mean hemoglobin was achieved and maintained within the target range in Japanese peritoneal dialysis participants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33964183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33964183", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34713596", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34739196", "endSection": "title" }, { "offsetInBeginSection": 1701, "offsetInEndSection": 1940, "text": "ONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34739196", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34739194", "endSection": "title" }, { "offsetInBeginSection": 2021, "offsetInEndSection": 2202, "text": "CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34739194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "Daprodustat (GSK1278863) is a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor in development for treatment of anemia of chronic kidney disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31640478", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "BACKGROUND: Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treatment of anemia associated with chronic kidney disease (CKD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27978511", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia of chronic kidney disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31306555", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 428, "text": "Daprodustat is under development as an emerging new class of agents for the treatment of anemia associated with chronic kidney disease (CKD).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32250021", "endSection": "abstract" }, { "offsetInBeginSection": 1822, "offsetInEndSection": 1960, "text": "Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33597868", "endSection": "abstract" }, { "offsetInBeginSection": 1961, "offsetInEndSection": 2046, "text": "And daprodustat may become an effective alternative for treatment of anemia with CKD.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33597868", "endSection": "abstract" } ] }, { "body": "Where is the the protein perforin localized?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33710487", "http://www.ncbi.nlm.nih.gov/pubmed/33884612", "http://www.ncbi.nlm.nih.gov/pubmed/33410220", "http://www.ncbi.nlm.nih.gov/pubmed/33467515" ], "ideal_answer": [ "Perforin are stored inside the leukocytes in secretory granules." ], "exact_answer": [ "In secretory granules" ], "type": "factoid", "id": "6217da133a8413c653000026", "snippets": [ { "offsetInBeginSection": 139, "offsetInEndSection": 220, "text": " a family of pore-forming proteins (PFPs), known as perforin like proteins (PLPs)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33467515", "endSection": "abstract" }, { "offsetInBeginSection": 943, "offsetInEndSection": 1000, "text": "cytotoxic granules (granzyme B, granulysin, and perforin)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33410220", "endSection": "abstract" }, { "offsetInBeginSection": 355, "offsetInEndSection": 434, "text": "Granzyme B and perforin are stored inside the leukocytes in secretory granules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33710487", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 260, "text": "T cells produce effector molecules that are either directly cytotoxic, such as granzymes, perforin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33884612", "endSection": "abstract" } ] }, { "body": "Is REGN5458 a single-targeted antibody?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33651100" ], "ideal_answer": [ "No, REGN5458 is a bispecific antibody." ], "exact_answer": "no", "type": "yesno", "id": "621218353a8413c653000013", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 418, "text": "CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33651100", "endSection": "abstract" } ] }, { "body": "Which disease is associated with X-linked recessive TLR7 deficiency?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34413140" ], "ideal_answer": [ "X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years.", "COVID-19 pneumonia", "Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years.", "COVID-19" ], "exact_answer": [ "critical COVID-19 pneumonia" ], "type": "factoid", "id": "62190bac3a8413c653000034", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34413140", "endSection": "title" }, { "offsetInBeginSection": 1352, "offsetInEndSection": 1638, "text": "Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34413140", "endSection": "abstract" } ] }, { "body": "Is Benralizumab effective for Chronic Spontaneous Urticaria?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32224275", "http://www.ncbi.nlm.nih.gov/pubmed/31446134", "http://www.ncbi.nlm.nih.gov/pubmed/30015639", "http://www.ncbi.nlm.nih.gov/pubmed/33685605" ], "ideal_answer": [ "Yes, the anti-IL-5 antibody benralizumab has been reported to reduce Chronic Spontaneous Urticaria symptoms." ], "exact_answer": "yes", "type": "yesno", "id": "6020a7391cb411341a00007e", "snippets": [ { "offsetInBeginSection": 1038, "offsetInEndSection": 1235, "text": "Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32224275", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1163, "text": "The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30015639", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1007, "text": "f-label use of dupilumab, reslizumab, mepolizumab, and benralizumab can be effective in CU. Ligel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31446134", "endSection": "abstract" }, { "offsetInBeginSection": 1038, "offsetInEndSection": 1234, "text": "Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32224275", "endSection": "abstract" }, { "offsetInBeginSection": 1052, "offsetInEndSection": 1252, "text": "ments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. Clearly, a new pi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32224275", "endSection": "abstract" }, { "offsetInBeginSection": 730, "offsetInEndSection": 939, "text": "ormation on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we discuss", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33685605", "endSection": "abstract" }, { "offsetInBeginSection": 753, "offsetInEndSection": 1312, "text": ", B cells, T cells and eosinophils. The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab.SUMMARY: The ongoing clinical trials on new targets of treatment hold new hopes not only for a better care of the disease but also a better understan", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30015639", "endSection": "abstract" } ] }, { "body": "Do the proteins Talin and Amot interact?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34433061" ], "ideal_answer": [ "Yes,\nAmot binds Talin" ], "exact_answer": "yes", "type": "yesno", "id": "6217dd013a8413c65300002f", "snippets": [ { "offsetInBeginSection": 652, "offsetInEndSection": 759, "text": "we show that Amot binds Talin and is essential for relaying forces between fibronectin and the cytoskeleton", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34433061", "endSection": "abstract" } ] }, { "body": "Do RNA binding Proteins that bind to adenine uridine (AU)-rich elements (AREs) in the 5' untranslated region (UTR) of mRNAs (AU-RBPs) regulate the DNA Damage Response?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32655569", "http://www.ncbi.nlm.nih.gov/pubmed/12762222", "http://www.ncbi.nlm.nih.gov/pubmed/19520857", "http://www.ncbi.nlm.nih.gov/pubmed/17878526", "http://www.ncbi.nlm.nih.gov/pubmed/25483082", "http://www.ncbi.nlm.nih.gov/pubmed/22626558", "http://www.ncbi.nlm.nih.gov/pubmed/24423872", "http://www.ncbi.nlm.nih.gov/pubmed/27592685", "http://www.ncbi.nlm.nih.gov/pubmed/15358174", "http://www.ncbi.nlm.nih.gov/pubmed/27634883", "http://www.ncbi.nlm.nih.gov/pubmed/20881234", "http://www.ncbi.nlm.nih.gov/pubmed/21457063", "http://www.ncbi.nlm.nih.gov/pubmed/21729330", "http://www.ncbi.nlm.nih.gov/pubmed/21161418", "http://www.ncbi.nlm.nih.gov/pubmed/11103939", "http://www.ncbi.nlm.nih.gov/pubmed/25680182", "http://www.ncbi.nlm.nih.gov/pubmed/29109951", "http://www.ncbi.nlm.nih.gov/pubmed/12900401", "http://www.ncbi.nlm.nih.gov/pubmed/23383270", "http://www.ncbi.nlm.nih.gov/pubmed/32491174", "http://www.ncbi.nlm.nih.gov/pubmed/11280780", "http://www.ncbi.nlm.nih.gov/pubmed/24692066", "http://www.ncbi.nlm.nih.gov/pubmed/29168431", "http://www.ncbi.nlm.nih.gov/pubmed/33271327", "http://www.ncbi.nlm.nih.gov/pubmed/23946796" ], "ideal_answer": [ "RNA Binding Proteins (RBPs) that bind to adenine uridine (AU)-rich elements (AREs) in the 3' untranslated region (UTR) of mRNAs (AU-RBPs) have emerged as key players in regulating the DNA Damage Response (DDR) and preserving genome integrity.", "We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA." ], "exact_answer": "no", "type": "yesno", "id": "6220cbf83a8413c653000067", "snippets": [ { "offsetInBeginSection": 554, "offsetInEndSection": 678, "text": " We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483082", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 371, "text": "Bioinformatics analysis of the human SOD1 mRNA 3' untranslated region (3'UTR) demonstrated the presence of HuD binding adenine-uridine (AU)-rich instability-conferring elements (AREs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33271327", "endSection": "abstract" }, { "offsetInBeginSection": 481, "offsetInEndSection": 612, "text": "We found that AU-rich element RNA binding protein 1 (AUF1) directly binds to the Cry1 3'UTR and regulates translation of Cry1 mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24423872", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Adenylate/uridylate-rich elements (AREs) are the most common cis-regulatory elements in the 3'-untranslated region (UTR) of mRNAs, where they fine-tune turnover by mediating mRNA decay.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32491174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "HuR binding to AU-rich elements present in the 3' untranslated region of Classical swine fever virus.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21729330", "endSection": "title" }, { "offsetInBeginSection": 332, "offsetInEndSection": 650, "text": "Previous reports indicate that distinct RNA sequence in the BDNF 3'UTRs differentially regulates BDNF production in the brain to accommodate neuronal activity changes, conceivably through differential interactions with undefined trans-acting factors that regulate stability and translation of these BDNF mRNA isoforms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23383270", "endSection": "abstract" }, { "offsetInBeginSection": 116, "offsetInEndSection": 253, "text": "The 5' untranslated region (UTR) of CSFV contains the IRES, which is a highly structured element that recruits the translation machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21729330", "endSection": "abstract" }, { "offsetInBeginSection": 184, "offsetInEndSection": 375, "text": "Although AU-rich elements (AREs) in the 3'UTR of interleukin-6 (IL-6) mRNA dictate mRNA degradation, the role of TTP in the post-transcriptional regulation of IL-6 gene expression is unclear.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21457063", "endSection": "abstract" }, { "offsetInBeginSection": 284, "offsetInEndSection": 419, "text": "We cloned the full-length cDNA of rabbit RGS4, which contains a long 3'-untranslated region (UTR) with several AU-rich elements (AREs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20881234", "endSection": "abstract" }, { "offsetInBeginSection": 544, "offsetInEndSection": 688, "text": "Luciferase reporter assays demonstrate that HuR specifically regulates FOXO1 expression through AU-rich elements (AREs) within the FOXO1 3' UTR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23946796", "endSection": "abstract" }, { "offsetInBeginSection": 669, "offsetInEndSection": 837, "text": "Additionally, we demonstrated that RNPC1 could bind to PR mRNA via AU-rich elements (AREs) within PR 3'-untranslated region (3'-UTR) and then enhance PR mRNA stability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27634883", "endSection": "abstract" }, { "offsetInBeginSection": 266, "offsetInEndSection": 458, "text": "Here, we find that CXCR4 harbors AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR) that bind and respond to the RNA-binding proteins, tristetraprolin (TTP/ZFP36) and HuR (ELAVL1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24692066", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 366, "text": "These proteins bind to adenine uridine-rich element (ARE) in the 3'untranslated region of target messenger RNA and stimulate target degradation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32655569", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 410, "text": "t mRNAs. RNA-binding proteins can control mRNA stability by binding to AU- and U-rich elements located in the 3'-untranslated regions (3'-UTRs) of target", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22626558", "endSection": "abstract" }, { "offsetInBeginSection": 997, "offsetInEndSection": 1139, "text": "y RNA-binding proteins (RBPs) have been shown to recognize and bind to mRNAs that contains AREs generally present in the 3'UTR of mRNAs. RBPs ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17878526", "endSection": "abstract" }, { "offsetInBeginSection": 1248, "offsetInEndSection": 1389, "text": "at AREs in the 3'UTR control TSP-1 mRNA stability and that the RNA binding protein AUF1 participates in this control. These studies suggest t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21161418", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 605, "text": "mber of the Elav family of RNA-binding proteins, has been implicated in this pathway through its binding to adenine and uridine (AU)-rich stability elements (ARE) located in the 3' untranslated regions (3'-UTRs) of the mRNA. Whereas three ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11280780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Hu proteins are RNA-binding proteins that are implicated in the control of stabilization, nuclear export, and/or translation of specific mRNAs with AU-rich elements (AREs) in the 3'-untranslated region. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15358174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "Post-transcriptional mRNA regulation by RNA binding proteins (RBPs) associated with AU-rich elements (AREs) present in the 3' untranslated region (3'UTR) of specific mRNAs modulates transcript stability and translation in eukaryotic cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680182", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "In the 3'-untranslated region, the destabilizing adenine-uridine (AU)-rich elements (AREs) control the expression of several transcripts through interactions with ARE-binding proteins (AUBPs) and RNA degradation machinery.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19520857", "endSection": "abstract" }, { "offsetInBeginSection": 220, "offsetInEndSection": 369, "text": "The AU/U-rich element-binding protein HuR has been shown to bind to p53 mRNA 3'UTR and enhance translation in response to DNA-damaging UVC radiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27592685", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The AUF1 (hnRNPD) and HuR (ELAV-like) proteins, potential trans-acting factors for regulated mRNA decay, bind in vitro to A+U-rich elements (AREs) found in the 3' untranslated region (3' UTR) of many labile transcripts.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11103939", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 322, "text": "NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29168431", "endSection": "abstract" }, { "offsetInBeginSection": 555, "offsetInEndSection": 678, "text": "We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25483082", "endSection": "abstract" }, { "offsetInBeginSection": 410, "offsetInEndSection": 656, "text": "Secondly, the degradation of some mRNAs related to immune responses has been reported to be regulated by binding of RNA-binding proteins to adenylate uridylate-rich elements (AU-rich elements, AREs) located in the 3'-untranslated region (3'-UTR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12762222", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 385, "text": "Here, we review the interplay between six well-known RBPs (TTP, AUF-1, KSRP, HuR, TIA-1, and TIAR) that recognize AU-rich elements (AREs) at the 3' untranslated regions of mRNAs, namely ARE-RBPs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29109951", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Hu proteins have been shown to bind to AU-rich elements (AREs) in the 3'-untranslated region of unstable mRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12900401", "endSection": "abstract" } ] }, { "body": "Has CPX-351 been approved by the FDA and the EMA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34256819" ], "ideal_answer": [ "Yes, CPX-351 has been approved by the US FDA and the EMA." ], "exact_answer": "yes", "type": "yesno", "id": "6211566a3a8413c653000010", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 362, "text": "CPX-351 (United States: Vyxeos\u00ae; Europe: Vyxeos\u00ae Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34256819", "endSection": "abstract" } ] }, { "body": "What is the role of KAT7 in AML?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32764680" ], "ideal_answer": [ "KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements and more specifically driven by the MLL-X gene fusions.", "KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements." ], "type": "summary", "id": "620c2d743a8413c653000008", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32764680", "endSection": "title" }, { "offsetInBeginSection": 449, "offsetInEndSection": 840, "text": " Here we investigate the essentiality of lysine acetyltransferase KAT7 in AMLs driven by the MLL-X gene fusions. We found that KAT7 loss leads to a rapid and complete loss of both H3K14ac and H4K12ac marks, in association with reduced proliferation, increased apoptosis, and differentiation of AML cells. Acetyltransferase activity of KAT7 is essential for the proliferation of these cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32764680", "endSection": "abstract" }, { "offsetInBeginSection": 562, "offsetInEndSection": 753, "text": "We found that KAT7 loss leads to a rapid and complete loss of both H3K14ac and H4K12ac marks, in association with reduced proliferation, increased apoptosis, and differentiation of AML cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32764680", "endSection": "abstract" } ] }, { "body": "Which drugs are included in the CAPIRI regimen?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/25534239", "http://www.ncbi.nlm.nih.gov/pubmed/33270098", "http://www.ncbi.nlm.nih.gov/pubmed/21300933", "http://www.ncbi.nlm.nih.gov/pubmed/30049885", "http://www.ncbi.nlm.nih.gov/pubmed/19526201", "http://www.ncbi.nlm.nih.gov/pubmed/26632033", "http://www.ncbi.nlm.nih.gov/pubmed/18361802", "http://www.ncbi.nlm.nih.gov/pubmed/31144145", "http://www.ncbi.nlm.nih.gov/pubmed/19713248", "http://www.ncbi.nlm.nih.gov/pubmed/27121793", "http://www.ncbi.nlm.nih.gov/pubmed/32703200", "http://www.ncbi.nlm.nih.gov/pubmed/25889149", "http://www.ncbi.nlm.nih.gov/pubmed/19152449", "http://www.ncbi.nlm.nih.gov/pubmed/22240792", "http://www.ncbi.nlm.nih.gov/pubmed/15684318", "http://www.ncbi.nlm.nih.gov/pubmed/28968978", "http://www.ncbi.nlm.nih.gov/pubmed/17325705" ], "ideal_answer": [ "CAPIRI regimen includes capecitabine plus irinotecan." ], "exact_answer": [ [ "capecitabine" ], [ "irinotecan" ] ], "type": "list", "id": "6027549d1cb411341a0000ea", "snippets": [ { "offsetInBeginSection": 263, "offsetInEndSection": 555, "text": "AXEPT, an Asian phase III study, showed that modified CAPIRI+BEV [capecitabine (CAP: 1600\u2009mg/m2), irinotecan (IRI: 200\u2009mg/m2), and BEV (7.5\u2009mg/m2)] was non-inferior to FOLFIRI+BEV as a second-line therapy for mCRC patients and was associated with a lower incidence of hematologic toxicities. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32703200", "endSection": "abstract" }, { "offsetInBeginSection": 221, "offsetInEndSection": 448, "text": "Objective: To compare the efficacy of capecitabine plus irinotecan (CAPIRI) vs irinotecan (IRI) alone in patients with advanced gallbladder cancer (GBC) who have disease progression after gemcitabine-based first-line treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33270098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 240, "text": "BACKGROUND: Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31144145", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 345, "text": "PURPOSE: The aim of this randomized, multicenter, noncomparative, phase II trial was to investigate the efficacy and safety of two potential first-line treatments, capecitabine and oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine and irinotecan (CapIRI) plus bevacizumab, in Japanese patients with metastatic colorectal cancer (mCRC).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30049885", "endSection": "abstract" }, { "offsetInBeginSection": 408, "offsetInEndSection": 768, "text": "A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI)).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28968978", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 963, "text": "Among these patients, 90 received capecitabine monotherapy as first-line therapy, and 93 received capecitabine plus irinotecan (CAPIRI) therapy as part of the CAIRO phase III clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27121793", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 353, "text": "A nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26632033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26632033", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "The relative efficacy and safety of first-line metastatic colorectal cancer (mCRC) treatment regimens, capecitabine with irinotecan (CAPIRI) and 5-fluorouracil/leucovorin plus irinotecan (FOLFIRI), are not well defined.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534239", "endSection": "abstract" }, { "offsetInBeginSection": 382, "offsetInEndSection": 508, "text": "tients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regimen every 3 wk. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19152449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "Randomised phase-II trial of CAPIRI (capecitabine, irinotecan) plus bevacizumab vs FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) plus bevacizumab as first-line treatment of patients with unresectable/metastatic colorectal cancer (mCRC).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22240792", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26632033", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "PURPOSE: The AIO KRK-0104 randomized phase II trial investigated the efficacy and safety of cetuximab combined with capecitabine and irinotecan (CAPIRI) or capecitabine and oxaliplatin (CAPOX) in the first-line treatment of metastatic colorectal cancer (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300933", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 234, "text": "BACKGROUND: Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31144145", "endSection": "abstract" }, { "offsetInBeginSection": 1225, "offsetInEndSection": 1358, "text": "e capecitabine has been effectively and safely combined with irinotecan (CAPIRI) and/or oxaliplatin (CAPOX). Three randomized phase I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18361802", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "BACKGROUND: To determine the efficacy and tolerability of capecitabine combined with oxaliplatin (CAPOX) or irinotecan (CAPIRI) as first-line treatment in patients with advanced/metastatic colorectal cancer aged > or =", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19713248", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "PURPOSE: To establish the feasibility and efficacy of capecitabine in combination with weekly irinotecan (CAPIRI) with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15684318", "endSection": "abstract" }, { "offsetInBeginSection": 76, "offsetInEndSection": 357, "text": " nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Pati", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26632033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "The relative efficacy and safety of first-line metastatic colorectal cancer (mCRC) treatment regimens, capecitabine with irinotecan (CAPIRI) and 5-fluorouracil/leucovorin plus irinotecan (FOLFIRI), are not well defined. We id", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25534239", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25889149", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17325705", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17325705", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 492, "text": "ient clinics. Patients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regim", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19152449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 460, "text": "PURPOSE: To establish the feasibility and efficacy of capecitabine in combination with weekly irinotecan (CAPIRI) with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer.PATIENTS AND METHODS: Nineteen patients with rectal cancer clinical stage T3-4, Nx received weekly irinotecan 50 mg/m(2) (days 1, 8, 15, 22, 29) and two doses of capecitabine (days 1 through 38; dose level [DL] I, 500 mg/m(2) bid; DL II, 625 mg/m(2) bid) ac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15684318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 616, "text": "PURPOSE: The AIO KRK-0104 randomized phase II trial investigated the efficacy and safety of cetuximab combined with capecitabine and irinotecan (CAPIRI) or capecitabine and oxaliplatin (CAPOX) in the first-line treatment of metastatic colorectal cancer (mCRC).PATIENTS AND METHODS: A total of 185 patients with mCRC were randomly assigned to cetuximab (400 mg/m(2) day 1, followed by 250 mg/m(2) weekly) plus CAPIRI (irinotecan 200 mg/m(2), day 1; capecitabine 800 mg/m(2) twice daily days 1 through 14, every 3 weeks; or cetuximab plus CAPOX (oxaliplatin 130 mg/m(2) day 1; capecitabine 1,000 mg/m(2) twice daily da", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21300933", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 512, "text": "But, since the data regarding bevacizumab administered together with capecitabin, an oral fluoropyrimidine, and irinotecan in patients with mCRC is limited, we aimed to analyse the efficacy and safety of bevacizumab with capecitabine plus irinotecan (BEV-CAPIRI) regimen in mCRC patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19526201", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1333, "text": "The oral fluoropyrimidine capecitabine has been effectively and safely combined with irinotecan (CAPIRI) and/or oxaliplatin (CAPOX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18361802", "endSection": "abstract" } ] }, { "body": "What is the p-crAssphage?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33715349", "http://www.ncbi.nlm.nih.gov/pubmed/33594055", "http://www.ncbi.nlm.nih.gov/pubmed/33137401" ], "ideal_answer": [ "CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes." ], "type": "summary", "id": "621b45943a8413c653000039", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "crAssphages are a broad group of diverse bacteriophages in the order Caudovirales that have been found to be highly abundant in the human gastrointestinal tract. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33137401", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33594055", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 100, "text": " crAssphage has been proposed as a human-specific marker for tracking fecal contamination. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33715349", "endSection": "abstract" } ] }, { "body": "What is the function of Circular RNA (circRNA)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32059672", "http://www.ncbi.nlm.nih.gov/pubmed/34258296", "http://www.ncbi.nlm.nih.gov/pubmed/33715625", "http://www.ncbi.nlm.nih.gov/pubmed/28082450", "http://www.ncbi.nlm.nih.gov/pubmed/28969093", "http://www.ncbi.nlm.nih.gov/pubmed/31998941", "http://www.ncbi.nlm.nih.gov/pubmed/34699790", "http://www.ncbi.nlm.nih.gov/pubmed/28634583", "http://www.ncbi.nlm.nih.gov/pubmed/27616979", "http://www.ncbi.nlm.nih.gov/pubmed/34542406", "http://www.ncbi.nlm.nih.gov/pubmed/30550956", "http://www.ncbi.nlm.nih.gov/pubmed/32667692", "http://www.ncbi.nlm.nih.gov/pubmed/29387208", "http://www.ncbi.nlm.nih.gov/pubmed/34110722", "http://www.ncbi.nlm.nih.gov/pubmed/30791568", "http://www.ncbi.nlm.nih.gov/pubmed/33649838", "http://www.ncbi.nlm.nih.gov/pubmed/33065239", "http://www.ncbi.nlm.nih.gov/pubmed/28018143", "http://www.ncbi.nlm.nih.gov/pubmed/32018039", "http://www.ncbi.nlm.nih.gov/pubmed/34100450", "http://www.ncbi.nlm.nih.gov/pubmed/31897908", "http://www.ncbi.nlm.nih.gov/pubmed/31832126", "http://www.ncbi.nlm.nih.gov/pubmed/34296749", "http://www.ncbi.nlm.nih.gov/pubmed/34535136", "http://www.ncbi.nlm.nih.gov/pubmed/31178190", "http://www.ncbi.nlm.nih.gov/pubmed/29349062", "http://www.ncbi.nlm.nih.gov/pubmed/33537235", "http://www.ncbi.nlm.nih.gov/pubmed/33835457" ], "ideal_answer": [ "Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation as well as the pathogenesis of diseases. including cancer", "Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation." ], "type": "summary", "id": "62211ce03a8413c65300006e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34100450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Circular RNAs (circRNAs) are important for the development and regeneration of the nervous system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34699790", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "Circular RNAs (circRNAs) are a type of single-stranded RNA molecules that normally do not encode proteins. circRNAs are involved in many physiological processes as well as the pathogenesis of diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31897908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Circular RNAs (circRNAs) are covalently closed RNA molecules that have been linked to various diseases, including cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31998941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Circular RNAs (circRNA) have been reported as regulators involved in hepatocellular carcinoma (HCC), but their mechanism of activity remains unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32667692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Circular RNA (or circRNA) is a type of single-stranded covalently closed circular RNA molecule and play important roles in diverse biological pathways.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33835457", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Circular RNA (circRNA) is a type of noncoding RNA that can interact with miRNAs to regulate gene expression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34258296", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Aims: Circular RNA (circRNA) is a newly validated class of single-stranded RNA, ubiquitously expressed in mammalian tissues and possessing key functions including acting as microRNA sponges and as transcriptional regulators by binding to RNA-binding prote", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28082450", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "Circular RNA (circRNA) participates in regulation of gene transcription, while estrogen receptor alpha (ER\u03b1) and quercetin (QUE) positively regulate bone formation, but little is known about the correlation among circRNA, ER\u03b1 and QUE. In this", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33065239", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Background: Circular RNA (circRNA), a new class of noncoding RNA, has been shown to be important in silicosis due to its unique role as a transcription regulator or as a sponge of small RNA r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31832126", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Circular RNA (circRNA) is a highly stable, single-stranded, closed-loop RNA that works as RNA or as a protein decoy to regulate gene expression. In", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34296749", "endSection": "abstract" }, { "offsetInBeginSection": 436, "offsetInEndSection": 555, "text": " RNA (circRNA), a kind of stable ncRNA, plays important roles in regulating gene expression via various ways. To date, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32018039", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "BACKGROUND: Circular RNA (circRNA) plays an important role in regulating cell biological function and has been shown to be involved in cancer progression, including oral squamous cell carcino", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33715625", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Circular RNA (circRNA) have been suggested to contribute to regulating gene expression in various tissues and cells of eukaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31178190", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Circular RNA (circRNA), a kind of special endogenous RNA, has been shown to be implicated in crucial biological processes of multiple cancers as a gene regulator. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30791568", "endSection": "abstract" }, { "offsetInBeginSection": 421, "offsetInEndSection": 592, "text": "The most explored function of circRNAs is as master regulators of gene expression that act to sequester or \u00b4sponge\u00b4 other gene expression regulators, in particular miRNAs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30550956", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34542406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634583", "endSection": "abstract" }, { "offsetInBeginSection": 723, "offsetInEndSection": 921, "text": "These features confer numerous potential functions to circRNAs, such as acting as miRNA sponges, or binding to RNA-associated proteins to form RNA-protein complexes that regulate gene transcription.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634583", "endSection": "abstract" }, { "offsetInBeginSection": 922, "offsetInEndSection": 1161, "text": "It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28634583", "endSection": "abstract" }, { "offsetInBeginSection": 303, "offsetInEndSection": 538, "text": "Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535136", "endSection": "abstract" }, { "offsetInBeginSection": 440, "offsetInEndSection": 600, "text": "CircRNAs play important roles as miRNA sponges, gene transcription and expression regulators, RNA-binding protein (RBP) sponges and protein/peptide translators.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28969093", "endSection": "abstract" }, { "offsetInBeginSection": 683, "offsetInEndSection": 818, "text": "New functions for circRNAs are arising, including protein sequestration, transcriptional regulation, and potential functions in cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28018143", "endSection": "abstract" }, { "offsetInBeginSection": 564, "offsetInEndSection": 682, "text": "Several circRNAs have been shown to function as microRNA \"sponges\" to counteract microRNA mediated repression of mRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28018143", "endSection": "abstract" }, { "offsetInBeginSection": 444, "offsetInEndSection": 769, "text": "circRNAs function as miRNA/protein sponge, protein scaffold, protein recruitment, enhancer of protein function, as well as templates for translation involved in the regulation of transcription/splicing, translation, protein degradation, and pri-miRNA processing in human cancers and contributed to the pathogenesis of cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33537235", "endSection": "abstract" }, { "offsetInBeginSection": 192, "offsetInEndSection": 338, "text": "CircRNAs function as competing endogenous RNAs or microRNA sponges that regulate transcription and splicing, binding to proteins, and translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34110722", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Circular RNAs function as competing endogenous RNAs in multiple types of cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29387208", "endSection": "title" }, { "offsetInBeginSection": 410, "offsetInEndSection": 527, "text": "Generally, circRNAs function as microRNA (miRNA) sponges and have a regulatory role in transcription and translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29349062", "endSection": "abstract" }, { "offsetInBeginSection": 232, "offsetInEndSection": 382, "text": "CircRNAs play important roles in various biological functions as microRNA sponges, transcriptional regulators and combining with RNA binding proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32059672", "endSection": "abstract" }, { "offsetInBeginSection": 131, "offsetInEndSection": 352, "text": "circRNAs have been confirmed to play a vital role in various biological functions, acting as microRNA sponges and reservoirs, as well as combining with RNA\u2011binding proteins during the progression of multiple cancer types.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33649838", "endSection": "abstract" }, { "offsetInBeginSection": 401, "offsetInEndSection": 676, "text": "The exact functions of circRNAs remain poorly understood, but evidence from analysis of some circRNA molecules suggests that they could substantially contribute to the regulation of gene expression, particularly in architecturally complex and polarized cells such as neurons.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27616979", "endSection": "abstract" }, { "offsetInBeginSection": 689, "offsetInEndSection": 935, "text": "Presently, certain circRNAs have been reported to function as microRNA sponges and RNA-binding protein sponges to regulate downstream gene transcription, which suggests a potential for circRNAs in cancer diagnosis, prognosis and clinical therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29387208", "endSection": "abstract" } ] }, { "body": "Which one was the first chromone in clinical use?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24925412" ], "ideal_answer": [ "The first chromone in clinical use, khellin." ], "exact_answer": [ "Khellin" ], "type": "factoid", "id": "6206cfd5c9dfcb9c09000040", "snippets": [ { "offsetInBeginSection": 142, "offsetInEndSection": 322, "text": "The first chromone in clinical use, khellin, was extracted from the seeds of the plant Ammi visnaga, and had been used for centuries as a diuretic and as a smooth muscle relaxant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925412", "endSection": "abstract" } ] }, { "body": "Which resource is used for visualisation of non-covalent contacts?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29335563" ], "ideal_answer": [ "The Protein Contacts Atlas is an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. The Protein Contacts Atlas enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information. The Protein Contacts Atlas is available at http://www.mrc-lmb.cam.ac.uk/pca/ and also through PDBe.", "The Protein Contacts Atlas is an interactive resource of non-covalent contacts at different scales of organization: atoms, residues, secondary structures, secondary structure, subunits, and entire complexes." ], "exact_answer": [ "Protein Contacts Atlas" ], "type": "factoid", "id": "605fb19794d57fd879000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Visualization and analysis of non-covalent contacts using the Protein Contacts Atlas.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335563", "endSection": "title" }, { "offsetInBeginSection": 381, "offsetInEndSection": 1152, "text": "We present the Protein Contacts Atlas, an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. We developed multiple representations for visualization and analysis of non-covalent contacts at different scales of organization: atoms, residues, secondary structure, subunits, and entire complexes. The Protein Contacts Atlas enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information. The Protein Contacts Atlas is available at http://www.mrc-lmb.cam.ac.uk/pca/ and also through PDBe.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29335563", "endSection": "abstract" } ] }, { "body": "Which disease is treated with Emapalumab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34096649", "http://www.ncbi.nlm.nih.gov/pubmed/31537529", "http://www.ncbi.nlm.nih.gov/pubmed/33686916", "http://www.ncbi.nlm.nih.gov/pubmed/32374962", "http://www.ncbi.nlm.nih.gov/pubmed/32648854", "http://www.ncbi.nlm.nih.gov/pubmed/33484058", "http://www.ncbi.nlm.nih.gov/pubmed/32447592", "http://www.ncbi.nlm.nih.gov/pubmed/33424859", "http://www.ncbi.nlm.nih.gov/pubmed/30623346", "http://www.ncbi.nlm.nih.gov/pubmed/32817285" ], "ideal_answer": [ "Emapalumab is a human monoclonal antibody directed against interferon-\u03b3 (IFN-\u03b3) that was approved by the Food and Drug Administration for primary hemophagocytic lymphohistiocytosis (HLH)." ], "exact_answer": [ "primary hemophagocytic lymphohistiocytosis" ], "type": "factoid", "id": "60234dc61cb411341a000094", "snippets": [ { "offsetInBeginSection": 1117, "offsetInEndSection": 1283, "text": "All patients who received the complement blocker eculizumab in addition to the interferon gamma blocker emapalumab had complete resolution of their TMA and survived. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32447592", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32374962", "endSection": "title" }, { "offsetInBeginSection": 2045, "offsetInEndSection": 2167, "text": "CONCLUSIONS: Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32374962", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Emapalumab for the treatment of hemophagocytic lymphohistiocytosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648854", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Emapalumab-Igsz (Gamifant) is a human monoclonal antibody directed against interferon-\u03b3 (IFN-\u03b3), and the first Food and Drug Administration (FDA)-approved therapy for primary hemophagocytic lymphohistiocytosis (HLH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648854", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 809, "text": "Emapalumab is approved for treatment of primary HLH that is refractory, recurrent, progressing or intolerant to current HLH treatments in both adult and pediatric patients. FDA approval was based on the results of a phase II/III clinical trial evaluating the safety and efficacy of emapalumab in 34 pediatric patients with primary HLH, 27 of whom were refractory to current therapies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "Emapalumab, a fully human anti-IFN\u03b3 monoclonal antibody, has been approved in the US as second-line treatment of primary hemophagocytic lymphohistiocytosis (HLH) patients and has shown promise in patients with graft failure (GF) requiring a second allogeneic hematopoietic stem cell transplantation (HSCT).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32817285", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 348, "text": "Emapalumab is a fully human immunoglobulin G1 monoclonal antibody directed against interferon-\u03b3 (IFN-\u03b3), which in November 2018 received the first global approval for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance to HLH therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31537529", "endSection": "abstract" }, { "offsetInBeginSection": 1263, "offsetInEndSection": 1498, "text": "Available data support the use of emapalumab for treatment of pHLH patients with refractory, recurrent or progressive disease, or intolerance to conventional therapy, recently, leading to FDA approval of the drug for these indications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33424859", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 497, "text": "Emapalumab, a monoclonal antibody directed against IFN-\u03b3, is the first target therapy approved for primary HLH with refractory, recurrent or progressive disease or intolerance to conventional therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33686916", "endSection": "abstract" }, { "offsetInBeginSection": 761, "offsetInEndSection": 849, "text": "RT OPINION: Emapalumab is an effective treatment for HLH with a good safety profile. Its", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33686916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Emapalumab for the treatment of relapsed/refractory hemophagocytic lymphohistiocytosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31537529", "endSection": "title" }, { "offsetInBeginSection": 287, "offsetInEndSection": 581, "text": "Recently, the therapeutic potential of IFN-\u03b3 inhibition has been documented; emapalumab, an anti-IFN-\u03b3 monoclonal antibody, has been approved in the United States for treatment of primary HLH that is refractory, recurrent or progressive, or in patients with intolerance to conventional therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33484058", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 311, "text": "Emapalumab, a fully human anti-IFN\u03b3 monoclonal antibody, has been approved in the US as second-line treatment of primary hemophagocytic lymphohistiocytosis (HLH) patients and has shown promise in patients with graft failure (GF) requiring a second allogeneic hematopoietic stem cell transplantation (HSCT). The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32817285", "endSection": "abstract" }, { "offsetInBeginSection": 291, "offsetInEndSection": 493, "text": "role. Emapalumab, a monoclonal antibody directed against IFN-\u03b3, is the first target therapy approved for primary HLH with refractory, recurrent or progressive disease or intolerance to conventional ther", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33686916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 353, "text": "Emapalumab is a fully human immunoglobulin G1 monoclonal antibody directed against interferon-\u03b3 (IFN-\u03b3), which in November 2018 received the first global approval for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance to HLH therapy. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31537529", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Emapalumab-Igsz (Gamifant) is a human monoclonal antibody directed against interferon-\u03b3 (IFN-\u03b3), and the first Food and Drug Administration (FDA)-approved therapy for primary hemophagocytic lymphohistiocytosis (HLH). HLH", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648854", "endSection": "abstract" }, { "offsetInBeginSection": 295, "offsetInEndSection": 593, "text": ", the therapeutic potential of IFN-\u03b3 inhibition has been documented; emapalumab, an anti-IFN-\u03b3 monoclonal antibody, has been approved in the United States for treatment of primary HLH that is refractory, recurrent or progressive, or in patients with intolerance to conventional therapy. Moreover, r", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33484058", "endSection": "abstract" }, { "offsetInBeginSection": 224, "offsetInEndSection": 430, "text": "a disorder characterized by hypercytokinemia in the setting of unbridled immune activation, and emapalumab represents the first therapeutic developed to address the underlying pathophysiology of HLH. Emapal", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Emapalumab for the treatment of relapsed/refractory hemophagocytic lymphohistiocytosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31537529", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Emapalumab for adult and pediatric patients with hemophagocytic lymphohistiocytosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33686916", "endSection": "title" }, { "offsetInBeginSection": 313, "offsetInEndSection": 580, "text": "ember 2018, emapalumab received its first global approval in the USA, for the treatment of paediatric (newborn and older) and adult patients with primary HLH, who have refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. Emapalumab", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30623346", "endSection": "abstract" }, { "offsetInBeginSection": 1290, "offsetInEndSection": 1528, "text": "use of emapalumab for treatment of pHLH patients with refractory, recurrent or progressive disease, or intolerance to conventional therapy, recently, leading to FDA approval of the drug for these indications. Additional data are needed to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33424859", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 596, "text": "Emapalumab is approved for treatment of primary HLH that is refractory, recurrent, progressing or intolerant to current HLH treatments in both adult and pediatric patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648854", "endSection": "abstract" }, { "offsetInBeginSection": 1342, "offsetInEndSection": 1500, "text": "The novel agent, emapalumab (an anti-IFN-\u03b3 monoclonal antibody) can be used to treat EBV-HLH cases to avoid the risk of secondary malignancy due to etoposide.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34096649", "endSection": "abstract" }, { "offsetInBeginSection": 283, "offsetInEndSection": 581, "text": "hogenic role. Emapalumab, a monoclonal antibody directed against IFN-\u03b3, is the first target therapy approved for primary HLH with refractory, recurrent or progressive disease or intolerance to conventional therapy.AREAS COVERED: We reviewed the pharmacological characteristics, safety, efficacy and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33686916", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 306, "text": "Emapalumab is being developed by Novimmune and Swedish Orphan Biovitrum for the treatment of haemophagocytic lymphohistiocytosis (HLH).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30623346", "endSection": "abstract" }, { "offsetInBeginSection": 307, "offsetInEndSection": 569, "text": "In November 2018, emapalumab received its first global approval in the USA, for the treatment of paediatric (newborn and older) and adult patients with primary HLH, who have refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30623346", "endSection": "abstract" } ] }, { "body": "Do we find bacteriophages in the gut?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34560321", "http://www.ncbi.nlm.nih.gov/pubmed/33137401", "http://www.ncbi.nlm.nih.gov/pubmed/33465423", "http://www.ncbi.nlm.nih.gov/pubmed/33176253", "http://www.ncbi.nlm.nih.gov/pubmed/33171009" ], "ideal_answer": [ "yes,\nBacterial viruses (bacteriophages, phages) of the gut have increasingly become a focus in microbiome studies, with an understanding that they are likely key players in health and disease." ], "exact_answer": "yes", "type": "yesno", "id": "6217dc173a8413c65300002b", "snippets": [ { "offsetInBeginSection": 830, "offsetInEndSection": 935, "text": "a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34560321", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Bacterial viruses (bacteriophages, phages) of the gut have increasingly become a focus in microbiome studies, with an understanding that they are likely key players in health and disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33465423", "endSection": "abstract" }, { "offsetInBeginSection": 286, "offsetInEndSection": 459, "text": "Already without exogenous intervention, a multitude of phage-bacterial interactions occur within the human gut, some of which might play a direct role in disease progression", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33176253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "We are surrounded by microbes, mostly bacteria and their viruses or phages, on the inside and outside of our bodies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33171009", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 317, "text": "crAssphages are a broad group of diverse bacteriophages in the order Caudovirales that have been found to be highly abundant in the human gastrointestinal tract. Despite their high prevalence, we have an incomplete understanding of how crAssphages shape and respond to ecological and evolutionary dynamics in the gut.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33137401", "endSection": "abstract" } ] }, { "body": "What is the function of the protein encoded by PUMILIO1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21098481", "http://www.ncbi.nlm.nih.gov/pubmed/34541851", "http://www.ncbi.nlm.nih.gov/pubmed/16954190", "http://www.ncbi.nlm.nih.gov/pubmed/30289101", "http://www.ncbi.nlm.nih.gov/pubmed/21397187", "http://www.ncbi.nlm.nih.gov/pubmed/25768905", "http://www.ncbi.nlm.nih.gov/pubmed/34705895", "http://www.ncbi.nlm.nih.gov/pubmed/34531333", "http://www.ncbi.nlm.nih.gov/pubmed/33508364", "http://www.ncbi.nlm.nih.gov/pubmed/30256721", "http://www.ncbi.nlm.nih.gov/pubmed/25896760", "http://www.ncbi.nlm.nih.gov/pubmed/29490074", "http://www.ncbi.nlm.nih.gov/pubmed/17024422", "http://www.ncbi.nlm.nih.gov/pubmed/31897787", "http://www.ncbi.nlm.nih.gov/pubmed/32437472" ], "ideal_answer": [ "Pumilio1 (Pum1) has been shown to play key roles in translational regulation of target mRNAs in many systems of diverse organisms.", "Pumilio is a member of the highly conserved PUF family of RNA-binding proteins that function as a developmental regulator in diverse animal species. Pumilio1 (Pum1) has been shown to play key roles in translational regulation of target mRNAs in many systems of diverse organisms." ], "exact_answer": [ "developmental and translational regulator of RNA", "regulate specific target mRNAs posttranscriptionally", "translational regulation of target mRNAs", "RNA-binding proteins that function as a developmental regulator in diverse animal species." ], "type": "factoid", "id": "621fcaf93a8413c653000065", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Human Pumilio (hPUM) is a structurally well-analyzed RNA-binding protein that has been used recently for artificial RNA binding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34541851", "endSection": "abstract" }, { "offsetInBeginSection": 247, "offsetInEndSection": 456, "text": "A family of RBPs, which is known as the Pumilio-FBF (PUF) family, is highly conserved among different species and has been associated with the undifferentiated and differentiated states of different cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32437472", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 273, "text": " The RNA-binding domains of Pumilio/fem-3 mRNA binding factors (PUF domains) are programmable RNA binding scaffolds used to engineer artificial proteins that specifically modulate RNAs", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29490074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Pumilio is a member of the highly conserved PUF family of RNA-binding proteins that function as a developmental regulator in diverse animal species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25896760", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 243, "text": "Pumilio1 (Pum1) has been shown to play key roles in translational regulation of target mRNAs in many systems of diverse organisms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30289101", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Human PUMILIO1 (PUM1) and PUMILIO2 (PUM2) are members of the PUMILIO/FBF (PUF) family that regulate specific target mRNAs posttranscriptionally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21397187", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 377, "text": "We previously showed that Pumilio1 (Pum1) is specifically involved in the translational control of cyclin B1 mRNA during Xenopus oocyte maturation, in cooperation with cytoplasmic polyadenylation element-binding protein (CPEB).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098481", "endSection": "abstract" }, { "offsetInBeginSection": 260, "offsetInEndSection": 518, "text": "Seeking to understand how post-translational modification of ATAXIN1 levels influences disease, we discovered that the RNA-binding protein PUMILIO1 (PUM1) not only directly regulates ATAXIN1 but also plays an unexpectedly important role in neuronal function.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25768905", "endSection": "abstract" }, { "offsetInBeginSection": 133, "offsetInEndSection": 345, "text": "ilio-1 (PUM1) is an RNA binding protein whose regulatory role is by binding to the consensus 5'UGUANAUA3' sequence on the 3'UTR of the mRNA targets and post-transcriptionally repressing their expression. This stu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33508364", "endSection": "abstract" }, { "offsetInBeginSection": 254, "offsetInEndSection": 401, "text": "ighly conserved RNA-binding protein Pumilio-1 (PUM1) regulates mouse growth and cell proliferation, propelling us to examine its role in cancer. We", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34531333", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 380, "text": "e previously showed that Pumilio1 (Pum1) is specifically involved in the translational control of cyclin B1 mRNA during Xenopus oocyte maturation, in cooperation with cytoplasmic polyadenylation element-binding protein (CPEB). It", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Pumilio is a sequence-specific RNA-binding protein that regulates translation from the relevant mRNA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17024422", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 528, "text": "to understand how post-translational modification of ATAXIN1 levels influences disease, we discovered that the RNA-binding protein PUMILIO1 (PUM1) not only directly regulates ATAXIN1 but also plays an unexpectedly important role in neuronal function. Loss of P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25768905", "endSection": "abstract" }, { "offsetInBeginSection": 1114, "offsetInEndSection": 1261, "text": "st-transcriptional repressor Pumilio-1 was identified as a potent limiter of PrPC expression through the degradation of PRNP mRNA. Because of its h", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34705895", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "Pumilio is a member of the highly conserved PUF family of RNA-binding proteins that function as a developmental regulator in diverse animal species.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25896760", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 243, "text": "Mouse PUMILIO1 (PUM1) and PUMILIO2 (PUM2) belong to the PUF (Pumilio/FBF) family, a highly conserved RNA binding protein family whose homologues play critical roles in embryonic development and germ line stem cell maintenance in invertebrates.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30256721", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 311, "text": "Although the pumilio protein regulates the reproductive organ development in many species, its role in Schistosoma japonicum is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31897787", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 337, "text": "Two Pumilio genes, Pum1 and Pum2, have been identified in mammals and are found to be involved in sperm development, neuron development as well as human diseases such as neurodegeneration.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25896760", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 619, "text": "These data show that Pumilio1 can be used as a scaffold to engineer RNA-binding proteins with designed sequence specificity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16954190", "endSection": "abstract" }, { "offsetInBeginSection": 556, "offsetInEndSection": 942, "text": "To understand the role of these proteins in human ESCs (hESCs), we first assessed the influence of the silencing of PUM1 and PUM2 on pluripotency genes and found that the knockdown of Pumilio genes significantly decreased the OCT4 and NANOG mRNA levels and reduced the amount of nuclear OCT4, which suggests that Pumilio proteins play a role in the maintenance of pluripotency in hESCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32437472", "endSection": "abstract" } ] }, { "body": "What is CPX-351", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34256819" ], "ideal_answer": [ "CPX-351 (United States: Vyxeos\u00ae; Europe: Vyxeos\u00ae Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes." ], "type": "summary", "id": "6211557b3a8413c65300000f", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 363, "text": "CPX-351 (United States: Vyxeos\u00ae; Europe: Vyxeos\u00ae Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34256819", "endSection": "abstract" } ] }, { "body": "What is the prevalence of the inactivating AKT variant p.Pro50Thr in the Finnish population?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28341696" ], "ideal_answer": [ "1.1% frequency", "The P.Pro50Thr allele is present at 1.1% frequency in Finns but virtually absent in other ancestries.", "A study identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function." ], "exact_answer": [ "1.1%" ], "type": "factoid", "id": "6028f5851cb411341a0000ff", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1179, "text": "To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28341696", "endSection": "abstract" } ] }, { "body": "Which mutations are inhibited by Ripretinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33948116", "http://www.ncbi.nlm.nih.gov/pubmed/32578014", "http://www.ncbi.nlm.nih.gov/pubmed/33473249", "http://www.ncbi.nlm.nih.gov/pubmed/31755321", "http://www.ncbi.nlm.nih.gov/pubmed/32859585", "http://www.ncbi.nlm.nih.gov/pubmed/31085175", "http://www.ncbi.nlm.nih.gov/pubmed/34503977", "http://www.ncbi.nlm.nih.gov/pubmed/34391056", "http://www.ncbi.nlm.nih.gov/pubmed/33947686", "http://www.ncbi.nlm.nih.gov/pubmed/31033566", "http://www.ncbi.nlm.nih.gov/pubmed/33876372", "http://www.ncbi.nlm.nih.gov/pubmed/32511981", "http://www.ncbi.nlm.nih.gov/pubmed/32804590" ], "ideal_answer": [ "Ripretinib is a novel switch-control kinase inhibitor designed to inhibit a wide range of KIT and PDGFRA mutations." ], "exact_answer": [ [ "KIT" ], [ "PDGFRA" ] ], "type": "list", "id": "6025e3a71cb411341a0000bc", "snippets": [ { "offsetInBeginSection": 185, "offsetInEndSection": 300, "text": "Ripretinib is a novel switch-control kinase inhibitor designed to inhibit a wide range of KIT and PDGFRA mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32804590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "The KIT/PDGFRA Inhibitor Ripretinib Shows Signs of Activity in GIST.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32859585", "endSection": "title" }, { "offsetInBeginSection": 395, "offsetInEndSection": 503, "text": "Both avapritinib and ripretinib are more potent and more specific against various KIT and PDGFRA mutations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31033566", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31085175", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 286, "text": "Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31085175", "endSection": "abstract" }, { "offsetInBeginSection": 424, "offsetInEndSection": 656, "text": "Ripretinib inhibits all tested KIT and PDGFRA mutants, and notably is a type II kinase inhibitor demonstrated to broadly inhibit activation loop mutations in KIT and PDGFRA, previously thought only achievable with type I inhibitors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31085175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 285, "text": "Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31085175", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "Ripretinib (DCC-2618) is a novel, type II tyrosine switch control inhibitor designed to broadly inhibit activating and drug-resistant mutations in KIT and PDGFRA. Ripretinib has emerged as a promising investigation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31755321", "endSection": "abstract" }, { "offsetInBeginSection": 322, "offsetInEndSection": 483, "text": "Ripretinib inhibits KIT and PDGFRA kinase, including wild-type, primary and secondary mutations, as well as other kinases, such as PDGFRB, TIE2, VEGFR2 and BRAF.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32578014", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 321, "text": "Ripretinib (QINLOCK\u2122) is a novel type II tyrosine switch control inhibitor being developed by Deciphera Pharmaceuticals for the treatment of KIT proto-oncogene receptor tyrosine kinase (KIT)-driven and/or platelet derived growth factor receptor A (PDGFRA)-driven cancers, including gastrointestinal stromal tumour (GIST).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32578014", "endSection": "abstract" }, { "offsetInBeginSection": 1325, "offsetInEndSection": 1710, "text": ".0001; exon 9, P = 0.0023; exon 13, P < 0.0001; exon 17, P < 0.0001). Among patients with wild-type KIT/PDGFRA by tumor tissue, PFS ranged from 2 to 23 months for ripretinib versus 0.9 to 10.1 months for placebo.CONCLUSIONS: Ripretinib provided clinically meaningful activity across mutation subgroups in patients with advanced GIST, demonstrating that ripretinib inhibits a broad rang", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34503977", "endSection": "abstract" }, { "offsetInBeginSection": 737, "offsetInEndSection": 934, "text": "Ripretinib is a novel switch-pocket inhibitor with broad activity against KIT and PDGFRA oncoproteins and has recently demonstrated antitumoral activity across phase I to phase III clinical trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33473249", "endSection": "abstract" }, { "offsetInBeginSection": 185, "offsetInEndSection": 352, "text": "Ripretinib is a novel switch-control kinase inhibitor designed to inhibit a wide range of KIT and PDGFRA mutations.PATIENTS AND METHODS: This first-in-human, to our kn", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32804590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "PURPOSE: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor \u03b1 kinase signalling.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34391056", "endSection": "abstract" }, { "offsetInBeginSection": 235, "offsetInEndSection": 484, "text": "ours. We compared the efficacy and safety of ripretinib, a switch-control tyrosine kinase inhibitor active against a broad spectrum of KIT and PDGFRA mutations, with placebo in patients with previously treated, advanced gastrointestinal stromal tumo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32511981", "endSection": "abstract" }, { "offsetInBeginSection": 847, "offsetInEndSection": 1041, "text": " possible. Ripretinib - a novel switch-control TKI - inhibits many of the most common primary and secondary activating KIT and PDGFRA mutants involved in GIST progression through a dual mechanis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33948116", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge. Rip", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31085175", "endSection": "abstract" }, { "offsetInBeginSection": 563, "offsetInEndSection": 911, "text": "y, United States Federal and Drug Administration (FDA) approved two new tyrosine kinase inhibitors for the treatment of heavily pretreated advanced/unresectable GIST including avapritinib (a selective inhibitor for PDGFRA exon 18 mutation including D842V mutations) and ripretinib (a broad-spectrum kinase inhibitor of c-Kit and PDGFRA). In this ar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33876372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Ripretinib (DCC-2618) is a novel, type II tyrosine switch control inhibitor designed to broadly inhibit activating and drug-resistant mutations in KIT and PDGFRA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31755321", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1223, "text": "Ripretinib potently inhibits a broad spectrum of primary and drug-resistant KIT/PDGFRA mutants and is approved by the FDA for the treatment of adult patients with advanced GIST who have received previous treatment with 3 or more kinase inhibitors, including imatinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33947686", "endSection": "abstract" }, { "offsetInBeginSection": 858, "offsetInEndSection": 1053, "text": "Ripretinib - a novel switch-control TKI - inhibits many of the most common primary and secondary activating KIT and PDGFRA mutants involved in GIST progression through a dual mechanism of action.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33948116", "endSection": "abstract" }, { "offsetInBeginSection": 1355, "offsetInEndSection": 1766, "text": "n 13, P < 0.0001; exon 17, P < 0.0001). Among patients with wild-type KIT/PDGFRA by tumor tissue, PFS ranged from 2 to 23 months for ripretinib versus 0.9 to 10.1 months for placebo.CONCLUSIONS: Ripretinib provided clinically meaningful activity across mutation subgroups in patients with advanced GIST, demonstrating that ripretinib inhibits a broad range of KIT/PDGFRA mutations in patients with advanced GIST", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34503977", "endSection": "abstract" }, { "offsetInBeginSection": 229, "offsetInEndSection": 616, "text": "al tumours. We compared the efficacy and safety of ripretinib, a switch-control tyrosine kinase inhibitor active against a broad spectrum of KIT and PDGFRA mutations, with placebo in patients with previously treated, advanced gastrointestinal stromal tumours.METHODS: In this double-blind, randomised, placebo-controlled, phase 3 study, we enrolled adult patients in 29 specialised hospi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32511981", "endSection": "abstract" }, { "offsetInBeginSection": 176, "offsetInEndSection": 507, "text": "roteins. Ripretinib is a novel switch-control kinase inhibitor designed to inhibit a wide range of KIT and PDGFRA mutations.PATIENTS AND METHODS: This first-in-human, to our knowledge, phase I study of ripretinib (ClinicalTrials.gov identifier: NCT02571036) included a dose-escalation phase and subsequent expansion phase at the re", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32804590", "endSection": "abstract" } ] }, { "body": "What is known about the PYHIN proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29120406", "http://www.ncbi.nlm.nih.gov/pubmed/32760121", "http://www.ncbi.nlm.nih.gov/pubmed/25665578", "http://www.ncbi.nlm.nih.gov/pubmed/28931603", "http://www.ncbi.nlm.nih.gov/pubmed/32946794" ], "ideal_answer": [ "The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle.\nAbsent in melanoma 2 (AIM2) is a member of the PYHIN (pyrin and HIN domain-containing protein) family with important roles in sensing double-stranded DNA (dsDNA) and assembling the AIM2 inflammasome, which has wide-ranging, pro-inflammatory and pro-pyroptotic properties." ], "type": "summary", "id": "60490e321cb411341a000168", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Members of the family of pyrin and HIN domain containing (PYHIN) proteins play an emerging role in innate immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32760121", "endSection": "abstract" }, { "offsetInBeginSection": 1769, "offsetInEndSection": 1988, "text": " our data show that IFI16, PYHIN1 and MNDA restrict HIV-1 and other viral pathogens by interfering with Sp1-dependent gene expression and support an important role of nuclear PYHIN proteins in innate antiviral immunity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32760121", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 272, "text": "Absent in melanoma 2 (AIM2) is a member of the PYHIN (pyrin and HIN domain-containing protein) family with important roles in sensing double-stranded DNA (dsDNA) and assembling the AIM2 inflammasome, which has wide-ranging, pro-inflammatory and pro-pyroptotic properties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32946794", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 303, "text": "Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and hematopoitic interferon-inducible nuclear protein (HIN) domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29120406", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Members of the IFN-inducible PYHIN protein family, such as absent in melanoma-2 and IFN-\u03b3-inducible protein (IFI)16, bind dsDNA and form caspase-1-activating inflammasomes that are important in immunity to cytosolic bacteria, DNA viruses, or HIV. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28931603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25665578", "endSection": "abstract" } ] }, { "body": "What class of drugs is commonly associated with Drug-induced interstitial lung disease (DIILD)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/2185802", "http://www.ncbi.nlm.nih.gov/pubmed/34177523", "http://www.ncbi.nlm.nih.gov/pubmed/1327232", "http://www.ncbi.nlm.nih.gov/pubmed/29631763", "http://www.ncbi.nlm.nih.gov/pubmed/24231065", "http://www.ncbi.nlm.nih.gov/pubmed/8765915", "http://www.ncbi.nlm.nih.gov/pubmed/10992015", "http://www.ncbi.nlm.nih.gov/pubmed/22189216", "http://www.ncbi.nlm.nih.gov/pubmed/17545850", "http://www.ncbi.nlm.nih.gov/pubmed/31963908", "http://www.ncbi.nlm.nih.gov/pubmed/31584970", "http://www.ncbi.nlm.nih.gov/pubmed/28050004", "http://www.ncbi.nlm.nih.gov/pubmed/30521972", "http://www.ncbi.nlm.nih.gov/pubmed/32598798", "http://www.ncbi.nlm.nih.gov/pubmed/22896776", "http://www.ncbi.nlm.nih.gov/pubmed/32874590", "http://www.ncbi.nlm.nih.gov/pubmed/30326612", "http://www.ncbi.nlm.nih.gov/pubmed/20298401" ], "ideal_answer": [ "[' Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity.']", "Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity", "Cytotoxic drugs are the most common cause of toxic lung disease." ], "exact_answer": [ "cytotoxic drugs" ], "type": "factoid", "id": "621ec0313a8413c65300005e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "The problem of the drug induced pulmonary toxicity (cytotoxic and non-cytotoxic drugs) is discussed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1327232", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 207, "text": "ulmonary drug toxicity is increasingly being diagnosed as a cause of acute and chronic lung disease. Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10992015", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Cytotoxic agents may cause interstitial or eosinophilic pneumonitis, alveolar proteinosis, pulmonary venous occlusive disease, pulmonary fibrosis, pneumothorax, or pulmonary oedema", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2185802", "endSection": "abstract" }, { "offsetInBeginSection": 1181, "offsetInEndSection": 1309, "text": "The cytotoxic drugs which are most often implicated in causing this are bleomycin, methotrexate, cyclophosphamide and busulfan. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8765915", "endSection": "abstract" }, { "offsetInBeginSection": 1730, "offsetInEndSection": 1794, "text": "Cytotoxic drugs are the most common cause of toxic lung disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8765915", "endSection": "abstract" }, { "offsetInBeginSection": 772, "offsetInEndSection": 883, "text": "er drugs, followed by rheumatology drugs, amiodarone and antibiotics, were the most common causes of DIILD. The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30326612", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Drug-induced interstitial lung disease (DIILD) is a serious side effect of chemotherapy in cancer patients with an extremely high mortality rate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31584970", "endSection": "abstract" }, { "offsetInBeginSection": 1032, "offsetInEndSection": 1270, "text": "Furthermore, in a subgroup analysis of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-induced interstitial lung disease (ILD), we observed seven candidate SNVs that were possibly associated with ILD (P < 0.00001).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31584970", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Drug-induced interstitial lung disease (DI-ILD) is a rare, yet life-threatening complication associated with tyrosine-kinase inhibitor (TKI) therapy. Thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34177523", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Drug-induced interstitial lung disease associated with dasatinib coinciding with active tuberculosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32874590", "endSection": "title" }, { "offsetInBeginSection": 821, "offsetInEndSection": 945, "text": "s was added. It is known that drug-induced ILD and susceptibility to infection associated with dasatinib occur in a dose-dep", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32874590", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "INTRODUCTION: The study objective was to determine the incidence and characteristics of drug-induced interstitial lung disease (ILD) associated with an orally available small-molecule tyrosine kinase inhibitor, crizotinib, in a real-world clinic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30521972", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "INTRODUCTION: Although gefitinib used for the treatment of non-small-cell lung cancer is a well-known cause of interstitial lung disease (ILD), few case reports on erlotinib-induced ILD have", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20298401", "endSection": "abstract" }, { "offsetInBeginSection": 310, "offsetInEndSection": 462, "text": "Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22896776", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "INTRODUCTION: A rare but serious complication of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is a lung injury syndrome commonly referred to as a drug-induced interstitial lung ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17545850", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "BACKGROUND: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31963908", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "OBJECTIVE: To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice.METHODS: We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010-2012 and EULAR 2010-2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231065", "endSection": "abstract" }, { "offsetInBeginSection": 434, "offsetInEndSection": 804, "text": "13 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA pat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24231065", "endSection": "abstract" }, { "offsetInBeginSection": 956, "offsetInEndSection": 1114, "text": "Drugs that are more commonly associated with lung toxicity include nitrofurantoin, amiodarone, and chemotherapeutic agents such as bleomycin and methotrexate.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29631763", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Drug-induced interstitial lung disease (D-ILD) can be caused by various drugs, including antibiotics, amiodarone, antitumor, rheumatological and non-steroidal anti-inflammatory drugs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32598798", "endSection": "abstract" } ] }, { "body": "What pathological phenotype could potentially concomitant pomegranate juice and rosuvastatin use cause?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/16923466" ], "ideal_answer": [ "Concomitant use of rosuvastatin and pomegranate juice has been hypothesized to be associated with the development of rhabdomyolysis in a case report." ], "exact_answer": [ "Rhabdomyolysis" ], "type": "factoid", "id": "6206b399c9dfcb9c09000039", "snippets": [ { "offsetInBeginSection": 365, "offsetInEndSection": 680, "text": "In conclusion, because both grapefruit and pomegranate juice are known to inhibit intestinal cytochrome P450 3A4, this report suggests that pomegranate juice may increase the risk of rhabdomyolysis during rosuvastatin treatment, despite the fact that rosuvastatin is not known to be metabolized by hepatic P450 3A4.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16923466", "endSection": "abstract" } ] }, { "body": "Which tool has been developed to discover VNTR-associated deletions?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34864893" ], "ideal_answer": [ "\u03a4rfermikit is a software tool designed to detect deletions larger than 50\u2009bp occurring in Variable Number Tandem Repeats (VNTRs) using Illumina DNA sequencing reads. In such regions, it achieves a better trade-off between sensitivity and false discovery than a state-of-the-art structural variation (SV) caller, Manta, and complements it by recovering a significant number of deletions that Manta missed. trfermikit is based upon the fermikit pipeline, which performs read assembly, maps the assembly to the reference genome, and calls variants from the alignment." ], "exact_answer": [ "trfermikit" ], "type": "factoid", "id": "621911323a8413c653000038", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "trfermikit: a tool to discover VNTR-associated deletions.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864893", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 582, "text": "We present trfermikit, a software tool designed to detect deletions larger than 50\u2009bp occurring in Variable Number Tandem Repeats (VNTRs) using Illumina DNA sequencing reads. In such regions, it achieves a better trade-off between sensitivity and false discovery than a state-of-the-art structural variation (SV) caller, Manta, and complements it by recovering a significant number of deletions that Manta missed. trfermikit is based upon the fermikit pipeline, which performs read assembly, maps the assembly to the reference genome, and calls variants from the alignment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "RESULTS: We present trfermikit, a software tool designed to detect deletions larger than 50\u2009bp occurring in Variable Number Tandem Repeats (VNTRs) using Illumina DNA sequencing reads.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "RESULTS: We present trfermikit, a software tool designed to detect deletions larger than 50\u2009bp occurring in Variable Number Tandem Repeats (VNTRs) using Illumina DNA sequencing", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864893", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 584, "text": "trfermikit is based upon the fermikit pipeline, which performs read assembly, maps the assembly to the reference genome, and calls variants from the alignment.AV", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864893", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "RESULTS: We present trfermikit, a software tool designed to detect deletions larger than 50\u2009bp occurring in Variable Number Tandem Repeats (VNTRs) using Illumina DNA sequenci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864893", "endSection": "abstract" } ] }, { "body": "Is tirabrutinib effective for lymphoma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32583848", "http://www.ncbi.nlm.nih.gov/pubmed/30815927", "http://www.ncbi.nlm.nih.gov/pubmed/33902692", "http://www.ncbi.nlm.nih.gov/pubmed/33851691", "http://www.ncbi.nlm.nih.gov/pubmed/34615748", "http://www.ncbi.nlm.nih.gov/pubmed/32382949" ], "ideal_answer": [ "Yes, tirabrutinib appears to be effective for lymphoma. It was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma." ], "exact_answer": "yes", "type": "yesno", "id": "601d6fe11cb411341a000033", "snippets": [ { "offsetInBeginSection": 420, "offsetInEndSection": 1106, "text": "In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also under regulatory review in Japan for the treatment of Waldenstr\u00f6m's macroglobulinemia and lymphoplasmacytic lymphoma. Clinical development is underway in the USA, Europe and Japan for autoimmune disorders, chronic lymphocytic leukaemia, B cell lymphoma, Sjogren's syndrome, pemphigus and rheumatoid arthritis. This article summarizes the milestones in the development of tirabrutinib leading to the first approval of tirabrutinib for the treatment of recurrent or refractory primary central nervous system lymphoma in Japan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32382949", "endSection": "abstract" }, { "offsetInBeginSection": 1570, "offsetInEndSection": 1680, "text": "CONCLUSION: These data indicate favorable efficacy of tirabrutinib in patients with relapsed/refractory PCNSL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32583848", "endSection": "abstract" }, { "offsetInBeginSection": 1621, "offsetInEndSection": 1702, "text": "Tirabrutinib was well tolerated and showed promising efficacy for B-cell NHL/CLL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30815927", "endSection": "abstract" }, { "offsetInBeginSection": 442, "offsetInEndSection": 582, "text": "rabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32382949", "endSection": "abstract" }, { "offsetInBeginSection": 947, "offsetInEndSection": 1211, "text": "Here, we provide a comprehensive review of the preclinical and clinical activity of tirabrutinib, a drug approved in Japan for relapsed or refractory primary central nervous system lymphoma and all lines of Waldenstr\u00f6m macroglobulinemia/lymphoplasmacytic lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33851691", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Tirabrutinib (ONO/GS-4059; Ono Pharmaceutical) is a newly developed drug that selectively and irreversibly inhibits Bruton's tyrosine kinase (BTK) and has been approved in Japan for treating relapsed/refractory primary central nervous system lymphoma (PCNSL).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33902692", "endSection": "abstract" }, { "offsetInBeginSection": 359, "offsetInEndSection": 543, "text": "A 64-year-old patient with recurrent PCNSL enrolled in the phase I/II clinical trial of tirabrutinib, a second-generation BTK inhibitor designed for treating relapsed/refractory PCNSL.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33902692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 252, "text": "BACKGROUND: The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).M", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32583848", "endSection": "abstract" }, { "offsetInBeginSection": 428, "offsetInEndSection": 568, "text": " 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabru", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32382949", "endSection": "abstract" }, { "offsetInBeginSection": 900, "offsetInEndSection": 1231, "text": "ine kinase inhibitor tirabrutinib (for relapsed and refractory PCNSL) and high-dose chemotherapy with autologous stem cell transplantation support using thiotepa and busulfan (BuTT) were approved by the Japanese Ministry of Health and Welfare in March 2020 and has recently become available for clinical practice. While these novel", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34615748", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 399, "text": "BACKGROUND: The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).METHODS: Patients with relapsed/refractory PCNSL, Karnofsky performance status \u226570, and normal end-organ function received tirabrutinib 320 and 480 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32583848", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Histological verification of the treatment effect of tirabrutinib for relapsed/refractory primary central nervous system lymphoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33902692", "endSection": "title" }, { "offsetInBeginSection": 420, "offsetInEndSection": 560, "text": "In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32382949", "endSection": "abstract" } ] }, { "body": "Is covid-19 induced anosmia caused by disruption of nuclear architecture?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33594368" ], "ideal_answer": [ "Yes. Disruption of nuclear architecture is a cause of COVID-19 induced anosmia." ], "exact_answer": "yes", "type": "yesno", "id": "620155b6c9dfcb9c09000024", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 74, "text": "Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33594368", "endSection": "title" }, { "offsetInBeginSection": 284, "offsetInEndSection": 1155, "text": "Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33594368", "endSection": "abstract" } ] }, { "body": "What is the mechanism of action of Toripalimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34603452", "http://www.ncbi.nlm.nih.gov/pubmed/30892132", "http://www.ncbi.nlm.nih.gov/pubmed/34894461", "http://www.ncbi.nlm.nih.gov/pubmed/34521188", "http://www.ncbi.nlm.nih.gov/pubmed/33492986", "http://www.ncbi.nlm.nih.gov/pubmed/30805896", "http://www.ncbi.nlm.nih.gov/pubmed/32224416", "http://www.ncbi.nlm.nih.gov/pubmed/34504425", "http://www.ncbi.nlm.nih.gov/pubmed/32406293", "http://www.ncbi.nlm.nih.gov/pubmed/32943323", "http://www.ncbi.nlm.nih.gov/pubmed/34678907", "http://www.ncbi.nlm.nih.gov/pubmed/32589350", "http://www.ncbi.nlm.nih.gov/pubmed/32487680", "http://www.ncbi.nlm.nih.gov/pubmed/32874831", "http://www.ncbi.nlm.nih.gov/pubmed/31403867", "http://www.ncbi.nlm.nih.gov/pubmed/31236579", "http://www.ncbi.nlm.nih.gov/pubmed/34632814", "http://www.ncbi.nlm.nih.gov/pubmed/32445174", "http://www.ncbi.nlm.nih.gov/pubmed/34532490" ], "ideal_answer": [ "Toripalimab is IgG4 monoclonal antibody targeting PD-1, which has been approved for treatment of patients with metastatic melanoma after previous systemic therapy." ], "type": "summary", "id": "61f7d6db882a024a10000037", "snippets": [ { "offsetInBeginSection": 490, "offsetInEndSection": 783, "text": "METHODS: Patients with advanced non-small cell lung cancer who were hospitalized in The Affiliated Cancer Hospital of Nanjing Medical University from October 2018 to August 2019 were selected to receive anti-PD-1 (pembrolizumab, sintilimab or toripalimab) monotherapy or combination regimens. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34521188", "endSection": "abstract" }, { "offsetInBeginSection": 778, "offsetInEndSection": 990, "text": "Here, we have presented a case of refractory ACC with lung metastases that was reduced after combinatorial treatment using the immune checkpoint inhibitor (ICI) toripalimab and anti-angiogenesis agent anlotinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34532490", "endSection": "abstract" }, { "offsetInBeginSection": 646, "offsetInEndSection": 742, "text": "Toripalimab is a type of anti-PD-1 monoclonal antibody produced by Junshi Biosciences in China. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34603452", "endSection": "abstract" }, { "offsetInBeginSection": 302, "offsetInEndSection": 826, "text": "Case summary: Herein, we described for the first time a case report of SBSR induced by anti-PD-1 therapy in a cervical cancer patient. In addition, we revised existing literature on anti-PD-1 induced cutaneous reactions. We reported a cervical cancer patient who was treated with four successive cycles of Sintilimab and Toripalimab injections and developed systemic rashes, bullae, and epidermal desquamation, which worsened and led to infection, eventually causing death after being unresponsive to aggressive treatments. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34504425", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Successful treatment of advanced pulmonary sarcomatoid carcinoma with the PD-1 inhibitor toripalimab: A case report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943323", "endSection": "title" }, { "offsetInBeginSection": 399, "offsetInEndSection": 570, "text": "Toripalimab (JS001) is IgG4 monoclonal antibody targeting PD-1, which has been approved for treatment of patients with metastatic melanoma after previous systemic therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32943323", "endSection": "abstract" }, { "offsetInBeginSection": 991, "offsetInEndSection": 1157, "text": "mber of studies have confirmed that PD-1 inhibitors, including toripalimab, are not as effective in mucosal and acral melanomas as in non-acral cutaneous subtype. Tor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32406293", "endSection": "abstract" }, { "offsetInBeginSection": 593, "offsetInEndSection": 853, "text": "Our analysis reveals that toripalimab mainly binds to the FG loop of PD-1 with an unconventionally long complementarity-determining region 3 loop of the heavy chain, which is distinct from the known binding epitopes of anti-PD-1 mAbs with structural evidences.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30892132", "endSection": "abstract" }, { "offsetInBeginSection": 336, "offsetInEndSection": 592, "text": "Here, we report the complex structure of PD-1 with toripalimab, a mAb that is approved by China National Medical Products Administration as a second-line treatment for melanoma and is under multiple Phase 1-Phase 3 clinical trials in both China and the US.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30892132", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "In this trial of programmed cell death-1 (PD-1) blockade with toripalimab in previously treated Chinese patients with melanoma, unique histologic and molecular features may explain why the objective response rate is lower than those defined in Western populations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32487680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30892132", "endSection": "title" }, { "offsetInBeginSection": 94, "offsetInEndSection": 315, "text": "NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33492986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "PURPOSE: This is a first-in-human phase I study investigating the safety and efficacy of toripalimab, a humanized monoclonal antibody against the programmed cell death-1 (PD-1) receptor, in Chinese patients with advanced or recurrent malignant tumor refractory to standard trea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32224416", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 395, "text": "apy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31236579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 255, "text": "Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30805896", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 266, "text": "In this trial of programmed cell death-1 (PD-1) blockade with toripalimab in previously treated Chinese patients with melanoma, unique histologic and molecular features may explain why the objective response rate is lower than those defined in Western populations. T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32487680", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Toripalimab is a monoclonal antibody targeting programmed cell death protein 1 (PD-1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32445174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30892132", "endSection": "title" }, { "offsetInBeginSection": 255, "offsetInEndSection": 475, "text": "uentially. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death protein-1 (PD-1), was approved by National Medical Product Administration in China in 2018 as second-line therapy for metastatic ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32406293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Toripalimab is a monoclonal antibody targeting programmed cell death protein 1 (PD-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32445174", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 300, "text": "Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30805896", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 217, "text": "Toripalimab is an\u00a0anti-PD-1 monoclonal antibody used for the treatment of some cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34632814", "endSection": "abstract" }, { "offsetInBeginSection": 634, "offsetInEndSection": 729, "text": " with ICIs. Toripalimab is a type of anti-PD-1 monoclonal antibody produced by Junshi Bioscienc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34603452", "endSection": "abstract" }, { "offsetInBeginSection": 1031, "offsetInEndSection": 1187, "text": "These findings benefit our understanding of the binding mechanisms of toripalimab to PD-1 and shed light for future development of biologics targeting PD-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30892132", "endSection": "abstract" }, { "offsetInBeginSection": 91, "offsetInEndSection": 306, "text": "a (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chem", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33492986", "endSection": "abstract" }, { "offsetInBeginSection": 1690, "offsetInEndSection": 1858, "text": " first dose of toripalimab.CONCLUSIONS: Toripalimab is a promising anti-PD-1 antibody, which was well tolerated and demonstrated anti-tumor activity in treatment-refrac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589350", "endSection": "abstract" }, { "offsetInBeginSection": 1262, "offsetInEndSection": 1410, "text": "by immunohistochemistry. The patient was treated with toripalimab (a PD-1 inhibitor) concurrently with radiotherapy for bone metastases.OUTCOMES: Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34678907", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Toripalimab, a humanized IgG4 monoclonal antibody (mAb) against programmed death receptor-1, is being extensively studied to treat various malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34894461", "endSection": "abstract" }, { "offsetInBeginSection": 1723, "offsetInEndSection": 1903, "text": "SIONS: Toripalimab is a promising anti-PD-1 antibody, which was well tolerated and demonstrated anti-tumor activity in treatment-refractory advanced solitary malignant tumors. Furt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589350", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32874831", "endSection": "abstract" }, { "offsetInBeginSection": 252, "offsetInEndSection": 706, "text": "sequentially. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death protein-1 (PD-1), was approved by National Medical Product Administration in China in 2018 as second-line therapy for metastatic melanoma.AREAS COVERED: This is a comprehensive review of the literature and studies of toripalimab in melanoma, including clinical trials and translational research.EXPERT OPINION: Toripalimab is not inferior to pembrolizumab as a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32406293", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32224416", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 426, "text": "PURPOSE: This is a first-in-human phase I study investigating the safety and efficacy of toripalimab, a humanized monoclonal antibody against the programmed cell death-1 (PD-1) receptor, in Chinese patients with advanced or recurrent malignant tumor refractory to standard treatment.PATIENTS AND METHODS: During dose escalation, patients received a single-dose intravenous infusion of toripalimab for 56 days followed by multi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32224416", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "A phase I study of toripalimab, an anti-PD-1 antibody, in patients with refractory malignant solid tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589350", "endSection": "title" }, { "offsetInBeginSection": 176, "offsetInEndSection": 610, "text": "unotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.PATIENTS AND METHODS: We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31236579", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31403867", "endSection": "title" } ] }, { "body": "Is taxilin a cancer marker?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/24091795", "http://www.ncbi.nlm.nih.gov/pubmed/32377534", "http://www.ncbi.nlm.nih.gov/pubmed/21042709", "http://www.ncbi.nlm.nih.gov/pubmed/28789367" ], "ideal_answer": [ "Yes,\n\u03b1-Taxilin, a binding partner of the syntaxin family, is a candidate tumor marker." ], "exact_answer": "yes", "type": "yesno", "id": "622dd1433a8413c6530000a5", "snippets": [ { "offsetInBeginSection": 770, "offsetInEndSection": 872, "text": "\u0391lpha-Taxilin (\u03b1-Taxilin) has been found as one of the novel, significantly up regulated protein in RA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32377534", "endSection": "abstract" }, { "offsetInBeginSection": 101, "offsetInEndSection": 238, "text": "Expression of \u03b1-taxilin has been implicated in the development of human glioblastoma, hepatocellular carcinoma and renal cell carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28789367", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "\u03b1-Taxilin, a binding partner of the syntaxin family, is a candidate tumor marker. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24091795", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Expression of \u03b1-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21042709", "endSection": "title" } ] }, { "body": "What are the symptoms of an incidental durotomy (ID).", "_type": "list", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10528385", "http://www.ncbi.nlm.nih.gov/pubmed/15260094" ], "_body": "What are the symptoms of an incidental durotomy (ID)", "ideal_answer": [ "Incidental durotomy can cause postural headaches, nausea, vomiting, dizziness, photophobia, tinnitus, and vertigo. Meningitis is a rare complication reported to occur with a frequency of 0.18%", "Incidental durotomy can cause postural headaches, nausea, vomiting, dizziness, photophobia, tinnitus, and vertigo." ], "exact_answer": [ [ "postural headaches" ], [ "vomiting" ], [ "dizziness" ], [ "photophobia" ], [ "tinnitus" ], [ "vertigo" ], [ "menningitis" ] ], "type": "list", "id": "6238a32a3a8413c6530000b9", "snippets": [ { "offsetInBeginSection": 268, "offsetInEndSection": 383, "text": "Incidental durotomy can cause postural headaches, nausea, vomiting, dizziness, photophobia, tinnitus, and vertigo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10528385", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Despite the frequency of dural tears in spinal surgery, meningitis is a rare complication reported to occur with a frequency of 0.18%.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15260094", "endSection": "abstract" }, { "offsetInBeginSection": 263, "offsetInEndSection": 413, "text": "ATA: Incidental durotomy can cause postural headaches, nausea, vomiting, dizziness, photophobia, tinnitus, and vertigo. These symptoms are believed to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10528385", "endSection": "abstract" } ] }, { "body": "Is PCAT6 a microRNA?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34620745" ], "ideal_answer": [ "No, PCAT6 is a long noncoding RNA." ], "exact_answer": "no", "type": "yesno", "id": "622668313a8413c653000087", "snippets": [ { "offsetInBeginSection": 240, "offsetInEndSection": 391, "text": "In this work, we investigated the role and regulatory mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in breast cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34620745", "endSection": "abstract" } ] }, { "body": "Is HDAC1 required for GATA-1 transcriptional activity?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34450641" ], "ideal_answer": [ "Yes. HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis." ], "exact_answer": "yes", "type": "yesno", "id": "6201a4edc9dfcb9c09000028", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34450641", "endSection": "title" }, { "offsetInBeginSection": 764, "offsetInEndSection": 1339, "text": "GATA-12RA knock-in (KI) mice suffer mild anemia and thrombocytopenia with accumulation of immature erythrocytes and megakaryocytes in bone marrow and spleen. Single cell RNA-seq analysis of Lin- cKit+ (LK) cells further reveal a profound change in cell subpopulations and signature gene expression patterns in HSC, myeloid progenitors, and erythroid/megakaryocyte clusters in KI mice. Thus, GATA-1 deacetylation and its interaction with HDAC1 modulates GATA-1 chromatin binding and transcriptional activity that control erythroid/megakaryocyte commitment and differentiation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34450641", "endSection": "abstract" } ] }, { "body": "Which enzyme is inhibited by Aramchol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32982112", "http://www.ncbi.nlm.nih.gov/pubmed/31931543", "http://www.ncbi.nlm.nih.gov/pubmed/29159325", "http://www.ncbi.nlm.nih.gov/pubmed/31013363", "http://www.ncbi.nlm.nih.gov/pubmed/34621052", "http://www.ncbi.nlm.nih.gov/pubmed/21044742", "http://www.ncbi.nlm.nih.gov/pubmed/34151243" ], "ideal_answer": [ "Arachidyl amido cholanoic acid (Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1 (SCD1) protein expression." ], "exact_answer": [ "hepatic stearoyl-CoA desaturase 1" ], "type": "factoid", "id": "61f7d683882a024a10000036", "snippets": [ { "offsetInBeginSection": 190, "offsetInEndSection": 354, "text": "Aramchol attenuates NASH in mouse models and decreases steatosis by downregulating the fatty acid synthetic enzyme stearoyl CoA desaturase 1 (SCD1) in hepatocytes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 380, "text": "Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34621052", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1965, "text": "Although the primary end point of a reduction in liver fat did not meet the prespecified significance level with Aramchol 600\u2009mg, the observed safety and changes in liver histology and enzymes provide a rationale for SCD1 modulation as a promising therapy for NASH and fibrosis and are being evaluated in an ongoing phase 3 program.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34621052", "endSection": "abstract" }, { "offsetInBeginSection": 621, "offsetInEndSection": 949, "text": "A number of phase 3 clinical trials are currently ongoing including Elafibranor, a dual PPAR \u03b1/\u03b4 agonist, Cenicriviroc, a CCR2/CCR5 chemokine antagonist, the nuclear bile acid receptor FXR agonist obeticholic acid, Aramchol, a fatty acid bile acid conjugate that modulates SCD-1, and Resmetrion, a liver-specific THR-\u03b2 agonist. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31931543", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "BACKGROUND: Arachidyl amido cholanoic acid (Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1 (SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982112", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 379, "text": "Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34621052", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 353, "text": "Aramchol attenuates NASH in mouse models and decreases steatosis by downregulating the fatty acid synthetic enzyme stearoyl CoA desaturase 1 (SCD1) in hepatocytes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "abstract" }, { "offsetInBeginSection": 1104, "offsetInEndSection": 1255, "text": "Aramchol downregulated stearoyl-CoA desaturase 1 (SCD1), a key enzyme involved in triglyceride biosynthesis whose loss enhances fatty acid \u03b2-oxidation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29159325", "endSection": "abstract" }, { "offsetInBeginSection": 1568, "offsetInEndSection": 1764, "text": "nclusions: Aramchol treatment improved steatohepatitis and fibrosis by 1) decreasing SCD1, and 2) increasing the flux through the transsulfuration pathway maintaining cellular redox homeostasis. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29159325", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "BACKGROUND: Arachidyl amido cholanoic acid (Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1 (SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982112", "endSection": "abstract" }, { "offsetInBeginSection": 205, "offsetInEndSection": 395, "text": "atherogenesis. The aim of the present study was to investigate whether inhibition of SCD by Aramchol, a fatty acid bile conjugate with known hypocholesterolemic effects, will affect atheroge", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21044742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "BACKGROUND: Arachidyl amido cholanoic acid (Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1 (SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatoh", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Aramchol downregulates stearoyl CoA-desaturase 1 in hepatic stellate cells to attenuate cellular fibrogenesis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "title" }, { "offsetInBeginSection": 1127, "offsetInEndSection": 1279, "text": "stearoyl-CoA desaturase 1 (SCD1), a key enzyme involved in triglyceride biosynthesis whose loss enhances fatty acid \u03b2-oxidation. Aramchol increased the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29159325", "endSection": "abstract" }, { "offsetInBeginSection": 173, "offsetInEndSection": 337, "text": "epatitis (NASH). Aramchol attenuates NASH in mouse models and decreases steatosis by downregulating the fatty acid synthetic enzyme stearoyl CoA desaturase 1 (SCD1)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "abstract" }, { "offsetInBeginSection": 1364, "offsetInEndSection": 1473, "text": "d increased PPARG mRNA expression.Conclusions: Aramchol downregulates SCD1 and elevates PPARG in HSCs, reduci", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Aramchol downregulates stearoyl CoA-desaturase 1 in hepatic stellate cells to attenuate cellular fibrogenesis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "title" }, { "offsetInBeginSection": 1474, "offsetInEndSection": 1666, "text": "g COL1A1 and ACTA2 mRNAs and COL1A1 secretion. These data suggest a direct inhibitory effect of Aramchol in HSCs through SCD1 inhibition, as part of a broader impact on both fibrogenic genes a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "abstract" }, { "offsetInBeginSection": 182, "offsetInEndSection": 332, "text": " hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents an", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34621052", "endSection": "abstract" }, { "offsetInBeginSection": 1064, "offsetInEndSection": 1214, "text": "atitis and fibrosis in 0.1MCD fed mice. Aramchol downregulated stearoyl-CoA desaturase 1 (SCD1), a key enzyme involved in triglyceride biosynthesis wh", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29159325", "endSection": "abstract" }, { "offsetInBeginSection": 215, "offsetInEndSection": 365, "text": "sis. The aim of the present study was to investigate whether inhibition of SCD by Aramchol, a fatty acid bile conjugate with known hypocholesterolemic", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21044742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31013363", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "BACKGROUND: Arachidyl amido cholanoic acid (Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1 (SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of stea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32982112", "endSection": "abstract" }, { "offsetInBeginSection": 1471, "offsetInEndSection": 1663, "text": "cing COL1A1 and ACTA2 mRNAs and COL1A1 secretion. These data suggest a direct inhibitory effect of Aramchol in HSCs through SCD1 inhibition, as part of a broader impact on both fibrogenic gene", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "abstract" }, { "offsetInBeginSection": 1287, "offsetInEndSection": 1470, "text": "ich catalyses cholesterol synthesis. In phHeps, Aramchol also reduced SCD1 and increased PPARG mRNA expression.Conclusions: Aramchol downregulates SCD1 and elevates PPARG in HSCs, red", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34151243", "endSection": "abstract" } ] }, { "body": "What is the cause of the Diamond Blackfan Anemia?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32643123", "http://www.ncbi.nlm.nih.gov/pubmed/32630050", "http://www.ncbi.nlm.nih.gov/pubmed/32620751" ], "ideal_answer": [ "Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency." ], "exact_answer": [ "Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency." ], "type": "factoid", "id": "622d17b83a8413c6530000a2", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32620751", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Diamond-Blackfan anemia is an autosomal dominant syndrome, characterized by anemia and a predisposition for malignancies. Ribosomal proteins are responsible for this syndrome, and the incidence of colorectal cancer in patients with this syndrome is higher than the general population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32643123", "endSection": "abstract" } ] }, { "body": "What are the functions of DNA and RNA G-quadruplexes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32545267", "http://www.ncbi.nlm.nih.gov/pubmed/26350216", "http://www.ncbi.nlm.nih.gov/pubmed/34148284", "http://www.ncbi.nlm.nih.gov/pubmed/32056246", "http://www.ncbi.nlm.nih.gov/pubmed/33021960", "http://www.ncbi.nlm.nih.gov/pubmed/22388183", "http://www.ncbi.nlm.nih.gov/pubmed/34285374", "http://www.ncbi.nlm.nih.gov/pubmed/22488917", "http://www.ncbi.nlm.nih.gov/pubmed/22376111", "http://www.ncbi.nlm.nih.gov/pubmed/34166611", "http://www.ncbi.nlm.nih.gov/pubmed/19330720", "http://www.ncbi.nlm.nih.gov/pubmed/25207541", "http://www.ncbi.nlm.nih.gov/pubmed/34162892", "http://www.ncbi.nlm.nih.gov/pubmed/21416921", "http://www.ncbi.nlm.nih.gov/pubmed/33733306", "http://www.ncbi.nlm.nih.gov/pubmed/23012368", "http://www.ncbi.nlm.nih.gov/pubmed/29517770", "http://www.ncbi.nlm.nih.gov/pubmed/23458775" ], "ideal_answer": [ "G-Quadruplex, a unique secondary structure in nucleic acids found throughout human genome, elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, RNAs and telomere, G-Quadruplex structure regulates transcription, translation, splicing, etc" ], "exact_answer": [ [ "transcription" ], [ "translation" ], [ "splicing" ], [ "RNA regulation" ] ], "type": "list", "id": "6220ce4c3a8413c653000068", "snippets": [ { "offsetInBeginSection": 189, "offsetInEndSection": 364, "text": "G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33021960", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory genomic regions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34166611", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 293, "text": "DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34162892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 306, "text": "G-Quadruplex, a unique secondary structure in nucleic acids found throughout human genome, elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, RNAs and telomere, G-Quadruplex structure regulates transcription, translation, splicing, etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34148284", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 387, "text": "G-quadruplexes (G4s) are higher-order structures formed by guanine-rich sequences of nucleic acids, such as the telomeric 5'-TTAGGG-3'/5'-UUAGGG-3' repeats and those in gene regulatory regions. G4s regulate various biological events, including replication, transcription, and translation. Imbalanced G4 dynamics is associated with diseases, such as cancer and neurodegenerative diseases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34285374", "endSection": "abstract" }, { "offsetInBeginSection": 791, "offsetInEndSection": 894, "text": "Further, the plausible functions of RNA G-quadruplexes such as translational suppression, splicing etc.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22376111", "endSection": "abstract" }, { "offsetInBeginSection": 155, "offsetInEndSection": 397, "text": "G-quadruplexes have various biological functions, including inhibition of telomerase and the regulation of gene transcription and translation, and have become an active target for drug development, particularly for novel anticancer therapies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19330720", "endSection": "abstract" }, { "offsetInBeginSection": 822, "offsetInEndSection": 1029, "text": "Here we briefly discuss various aspects of reporter assays followed by a review of available studies using reporter assays to understand the role and functions of DNA and RNA quadruplexes in gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22388183", "endSection": "abstract" }, { "offsetInBeginSection": 647, "offsetInEndSection": 864, "text": " review, we summarize recent evidence for the in vivo presence and function of DNA and RNA G-quadruplexes in various cellular pathways including DNA replication, gene expression and telomere maintenance. We also highl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26350216", "endSection": "abstract" }, { "offsetInBeginSection": 134, "offsetInEndSection": 334, "text": "im was to investigate their interaction with DNA and RNA G-quadruplexes, their uptake in malignant and nonmalignant cells, and their capacity to modulate gene expression and inhibit cell growth. Flow ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23458775", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 472, "text": "particular, G-quadruplexes occupy strategic locations in genomic DNA and both coding and noncoding RNA molecules, being involved in many essential cellular and organismal functions. In ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32545267", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Growing evidence indicates that RNA G-quadruplexes have important roles in various processes such as transcription, translation, regulation of telomere length, and formation of telomeric heterochromatin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29517770", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 484, "text": "RNA G-quadruplexes at these specific locations play important roles in key cellular functions, including telomere homeostasis and gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488917", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 949, "text": " the plausible functions of RNA G-quadruplexes such as translational suppression, splicing etc. are discussed in brief, suggesting scope for an extens", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22376111", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 341, "text": "Accumulating evidence indicates that G-quadruplexes serve important regulatory roles in fundamental biological processes such as DNA replication, transcription, and translation, while aberrant G-quadruplex formation is linked to genome instability and cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33733306", "endSection": "abstract" }, { "offsetInBeginSection": 485, "offsetInEndSection": 643, "text": "Indeed, RNA G-quadruplexes appear as important regulators of pre-mRNA processing (splicing and polyadenylation), RNA turnover, mRNA targeting and translation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22488917", "endSection": "abstract" }, { "offsetInBeginSection": 913, "offsetInEndSection": 1084, "text": "We show that G-quadruplexes formed by both (G(4)C(2))(4) RNA and DNA not only complex tightly with heme but also enhance its intrinsic peroxidase and oxidase propensities.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25207541", "endSection": "abstract" }, { "offsetInBeginSection": 802, "offsetInEndSection": 965, "text": "The formation of the DNA-RNA G-quadruplex causes a significant increase in the clonogenic capacity of cells and has an effect on inhibition of cellular senescence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23012368", "endSection": "abstract" }, { "offsetInBeginSection": 287, "offsetInEndSection": 473, "text": "Meanwhile, the different conformations of G-quadruplexes have certain influences on their biological functions, such as the inhibition of transcription, translation, and DNA replication.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32056246", "endSection": "abstract" }, { "offsetInBeginSection": 236, "offsetInEndSection": 471, "text": "G-quadruplex has been implicated by a lot of studies as an important structure in many biological processes including gene stability, telomere synthesis, transcriptional or translational regulation of gene expression and recombination.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21416921", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33733306", "endSection": "title" } ] }, { "body": "What is the effect of epiregulin expression in tumors?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30738695" ], "ideal_answer": [ "Epiregulin has elevated expression in a variety of human cancers. Epiregulin expression promotes tumor progression and metastasis and reduces patient survival." ], "type": "summary", "id": "6237aa3c3a8413c6530000b5", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 211, "text": "Epiregulin (EREG) is a novel family member of EGF-like ligands and have elevated expression in a variety of human cancers. EREG expression promotes tumor progression and metastasis and reduces patient survival. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30738695", "endSection": "abstract" }, { "offsetInBeginSection": 625, "offsetInEndSection": 1003, "text": "We found that EREG expression was significantly higher in GC tissues than in matched adjacent noncancerous tissues. High EREG protein expression in GC was significantly associated with TNM stage including tumor size, lymph node metastases and distant metastases as well as poor overall survival. These finding demonstrate that EREG is an independent prognostic biomarker for GC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30738695", "endSection": "abstract" } ] }, { "body": "Name scRNA-seq workflows which harness graph attention networks", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34512734", "http://www.ncbi.nlm.nih.gov/pubmed/34864884" ], "ideal_answer": [ "SCDRHA and CellVGAE" ], "exact_answer": [ [ "CellVGAE" ], [ "SCDRHA" ] ], "type": "list", "id": "621e5cf53a8413c65300004e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "SCDRHA: A scRNA-Seq Data Dimensionality Reduction Algorithm Based on Hierarchical Autoencoder.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34512734", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 922, "text": "To address this issue, in this paper, we propose a scRNA-seq data dimensionality reduction algorithm based on a hierarchical autoencoder, termed SCDRHA. The proposed SCDRHA consists of two core modules, where the first module is a deep count autoencoder (DCA) that is used to denoise data, and the second module is a graph autoencoder that projects the data into a low-dimensional space. Experimental results demonstrate that SCDRHA has better performance than existing state-of-the-art algorithms on dimension reduction and noise reduction in five real scRNA-seq datasets. Besides, SCDRHA can also dramatically improve the performance of data visualization and cell clustering.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34512734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "CellVGAE: an unsupervised scRNA-seq analysis workflow with graph attention networks.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864884", "endSection": "title" }, { "offsetInBeginSection": 497, "offsetInEndSection": 934, "text": "With the help of several case studies, we show that our model, named CellVGAE, can be effectively used for exploratory analysis even on challenging datasets, by extracting meaningful features from the data and providing the means to visualise and interpret different aspects of the model.RESULTS: We show that CellVGAE is more interpretable than existing scRNA-seq variational architectures by analysing the graph attention coefficients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864884", "endSection": "abstract" } ] }, { "body": "Which molecule is targeted by Fenebrutinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34750553", "http://www.ncbi.nlm.nih.gov/pubmed/31494233", "http://www.ncbi.nlm.nih.gov/pubmed/32832028", "http://www.ncbi.nlm.nih.gov/pubmed/32270926", "http://www.ncbi.nlm.nih.gov/pubmed/33806595", "http://www.ncbi.nlm.nih.gov/pubmed/31907670", "http://www.ncbi.nlm.nih.gov/pubmed/31446134", "http://www.ncbi.nlm.nih.gov/pubmed/34042314", "http://www.ncbi.nlm.nih.gov/pubmed/33777941", "http://www.ncbi.nlm.nih.gov/pubmed/31371481", "http://www.ncbi.nlm.nih.gov/pubmed/33689480" ], "ideal_answer": [ "Fenebrutinib is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK)." ], "exact_answer": [ "Bruton's tyrosine kinase" ], "type": "factoid", "id": "61f7d5a0882a024a10000035", "snippets": [ { "offsetInBeginSection": 600, "offsetInEndSection": 898, "text": "These inhibitors include four Syk inhibitors, Bay 61-3606, R406 (fostamatinib), entospletinib, TAK-659; four irreversible BTK inhibitors, ibrutinib, acalabrutinib, ONO-4059 (tirabrutinib), AVL-292 (spebrutinib); and four reversible BTK inhibitors, CG-806, BMS-935177, BMS-986195, and fenebrutinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33689480", "endSection": "abstract" }, { "offsetInBeginSection": 782, "offsetInEndSection": 1103, "text": "However, an increasing number of trials instead addresses autoimmunity and inflammation in multiple sclerosis, rheumatoid arthritis, pemphigus and systemic lupus erythematosus with the use of either irreversibly binding inhibitors, e.g., evobrutinib and tolebrutinib, or reversibly binding inhibitors, like fenebrutinib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33777941", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "OBJECTIVE: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34042314", "endSection": "abstract" }, { "offsetInBeginSection": 607, "offsetInEndSection": 1013, "text": "In contrast, no bleeding has been reported in clinical trials of other BTKi. These include the brain-penetrant irreversible tolebrutinib and evobrutinib (against multiple sclerosis), the irreversible branebrutinib, the reversible BMS-986142 and fenebrutinib (targeting rheumatoid arthritis and lupus erythematodes), and the reversible covalent rilzabrutinib (against pemphigus and immune thrombocytopenia).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33806595", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "Bruton's tyrosine kinase (BTK) is crucial for Fc\u03b5RI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34750553", "endSection": "abstract" }, { "offsetInBeginSection": 973, "offsetInEndSection": 1311, "text": "New therapeutics under investigation include IgG1 anti-IgE monoclonal antibodies (ligelizumab), chemoattractant rector-homologous molecule expressed on TH2 cells antagonists (AZD1981), Bruton tyrosine kinase inhibitors (fenebrutinib), anti-siglec-8 monoclonal antibody (AK002), and topical spleen tyrosine kinase inhibitors (GSK2646264). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31494233", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "Fenebrutinib (GDC-0853) is an orally administered small molecule inhibitor of Bruton's tyrosine kinase being investigated for treatment of rheumatoid arthritis in patients with inadequate responses to methotrexate (MTX).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31371481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Absence of Pharmacokinetic Interactions between the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib and Methotrexate.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31371481", "endSection": "title" }, { "offsetInBeginSection": 285, "offsetInEndSection": 560, "text": "In efforts to develop additional series of reversible Btk inhibitors for chronic immune diseases, we sought to differentiate from our clinical stage inhibitor fenebrutinib using cyclopropyl amide isosteres of the 2-aminopyridyl group to occupy the flat, lipophilic H2 pocket.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32832028", "endSection": "abstract" }, { "offsetInBeginSection": 979, "offsetInEndSection": 1338, "text": "erapeutics under investigation include IgG1 anti-IgE monoclonal antibodies (ligelizumab), chemoattractant rector-homologous molecule expressed on TH2 cells antagonists (AZD1981), Bruton tyrosine kinase inhibitors (fenebrutinib), anti-siglec-8 monoclonal antibody (AK002), and topical spleen tyrosine kinase inhibitors (GSK2646264). We review the mechanisms of", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31494233", "endSection": "abstract" }, { "offsetInBeginSection": 1103, "offsetInEndSection": 1430, "text": "promising drugs that are currently under development for CU are a chemoattractant receptor-homologous molecule expressed on TH2 cell antagonist, a monoclonal antibody to Siglec-8 (AK002), Bruton tyrosine kinase inhibitors (fenebrutinib and Lou064), a spleen tyrosine kinase inhibitor, and dupilumab. Promising targets of future", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31446134", "endSection": "abstract" }, { "offsetInBeginSection": 600, "offsetInEndSection": 897, "text": "These inhibitors include four Syk inhibitors, Bay 61-3606, R406 (fostamatinib), entospletinib, TAK-659; four irreversible BTK inhibitors, ibrutinib, acalabrutinib, ONO-4059 (tirabrutinib), AVL-292 (spebrutinib); and four reversible BTK inhibitors, CG-806, BMS-935177, BMS-986195, and fenebrutinib.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33689480", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "OBJECTIVE: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34042314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVE: To evaluate fenebrutinib, an oral and highly selective non-covalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthrit", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32270926", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "PURPOSE: Fenebrutinib (GDC-0853), a Bruton's tyrosine kinase (BTK) inhibitor was investigated in a Phase 2 clinical trial in patients with rheumatoid arthritis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31907670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 222, "text": "Fenebrutinib (GDC-0853) is an orally administered small molecule inhibitor of Bruton's tyrosine kinase being investigated for treatment of rheumatoid arthritis in patients with inadequate responses to methotrexate (MTX). T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31371481", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "OBJECTIVE: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine ki", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34042314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "PURPOSE: Fenebrutinib (GDC-0853), a Bruton's tyrosine kinase (BTK) inhibitor was investigated in a Phase 2 clinical trial in patients with rheumatoid arthri", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31907670", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "OBJECTIVE: To evaluate fenebrutinib, an oral and highly selective non-covalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32270926", "endSection": "abstract" }, { "offsetInBeginSection": 1370, "offsetInEndSection": 1610, "text": "utinib 200 mg twice daily. By week 48, patients treated with fenebrutinib had reduced levels of a BTK-dependent plasmablast RNA signature, anti-double-stranded DNA autoantibodies, total IgG, and IgM, as well as increased complement C4 level", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34042314", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 375, "text": "OBJECTIVE: To evaluate fenebrutinib, an oral and highly selective non-covalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA).METHODS: Patients with RA and inadequate response to methotrexate (cohort 1, n=480) were randomized to fenebrutinib (50 mg once daily, 150 mg once daily, 200 mg twice daily), 40 mg adalimumab every oth", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32270926", "endSection": "abstract" }, { "offsetInBeginSection": 175, "offsetInEndSection": 289, "text": "Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34750553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34042314", "endSection": "title" }, { "offsetInBeginSection": 921, "offsetInEndSection": 1258, "text": "essants; however, additional treatments are needed. New therapeutics under investigation include IgG1 anti-IgE monoclonal antibodies (ligelizumab), chemoattractant rector-homologous molecule expressed on TH2 cells antagonists (AZD1981), Bruton tyrosine kinase inhibitors (fenebrutinib), anti-siglec-8 monoclonal antibody (AK002), and top", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31494233", "endSection": "abstract" }, { "offsetInBeginSection": 1368, "offsetInEndSection": 1758, "text": "brutinib 200 mg twice daily. By week 48, patients treated with fenebrutinib had reduced levels of a BTK-dependent plasmablast RNA signature, anti-double-stranded DNA autoantibodies, total IgG, and IgM, as well as increased complement C4 levels, all relative to placebo.CONCLUSION: While fenebrutinib had an acceptable safety profile, the primary end point, SRI-4 response, was not met despi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34042314", "endSection": "abstract" } ] }, { "body": "What is Cereblon?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34588172", "http://www.ncbi.nlm.nih.gov/pubmed/34489457", "http://www.ncbi.nlm.nih.gov/pubmed/34553266", "http://www.ncbi.nlm.nih.gov/pubmed/34572892" ], "ideal_answer": [ "Cereblon (CRBN) is a substrate recognition protein in the E3-ligase ubiquitin complex. The binding target of CRBN varies according to tissues and cells, and the protein regulates various biological functions by regulating tissue-specific targets." ], "type": "summary", "id": "622d04da3a8413c65300009f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 247, "text": "Cereblon (CRBN) is a substrate recognition protein in the E3-ligase ubiquitin complex. The binding target of CRBN varies according to tissues and cells, and the protein regulates various biological functions by regulating tissue-specific targets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34553266", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The E3 ubiquitin ligase component, Cereblon, is an evolutionarily conserved regulator of Wnt signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34489457", "endSection": "title" }, { "offsetInBeginSection": 591, "offsetInEndSection": 662, "text": "the cereblon (CRBN) protein was discovered as a direct target of IMiDs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34572892", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Rapid Progress in the Use of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34572892", "endSection": "title" }, { "offsetInBeginSection": 1001, "offsetInEndSection": 1062, "text": "cereblon, a substrate receptor of the cullin-4 RING E3 ligase", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34588172", "endSection": "abstract" } ] }, { "body": "What is Abbreviated Injury Scale (AIS) used to determine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30841797", "http://www.ncbi.nlm.nih.gov/pubmed/17503572", "http://www.ncbi.nlm.nih.gov/pubmed/29137197", "http://www.ncbi.nlm.nih.gov/pubmed/30663437", "http://www.ncbi.nlm.nih.gov/pubmed/16060187", "http://www.ncbi.nlm.nih.gov/pubmed/27586096", "http://www.ncbi.nlm.nih.gov/pubmed/34469860", "http://www.ncbi.nlm.nih.gov/pubmed/8859913", "http://www.ncbi.nlm.nih.gov/pubmed/8861162", "http://www.ncbi.nlm.nih.gov/pubmed/20356359", "http://www.ncbi.nlm.nih.gov/pubmed/29930816", "http://www.ncbi.nlm.nih.gov/pubmed/3925257", "http://www.ncbi.nlm.nih.gov/pubmed/29320211", "http://www.ncbi.nlm.nih.gov/pubmed/20691038", "http://www.ncbi.nlm.nih.gov/pubmed/30624377", "http://www.ncbi.nlm.nih.gov/pubmed/10452467", "http://www.ncbi.nlm.nih.gov/pubmed/20376615", "http://www.ncbi.nlm.nih.gov/pubmed/17092503", "http://www.ncbi.nlm.nih.gov/pubmed/11320737", "http://www.ncbi.nlm.nih.gov/pubmed/7282320", "http://www.ncbi.nlm.nih.gov/pubmed/3339667" ], "ideal_answer": [ "The Abbreviated Injury Scale (AIS) is an objective anatomically-based injury severity scoring system that classifies each injury by body region on a 6 point scale. AIS is the system used to determine the Injury Severity Score (ISS) of the multiply injured trauma patient.\n\nAIS CLASSIFICATIONS\nThe AIS classifies individual injuries by body region as follows:\nAIS 1 \u2013 Minor\nAIS 2 \u2013 Moderate\nAIS 3 \u2013 Serious\nAIS 4 \u2013 Severe\nAIS 5 \u2013 Critical\nAIS 6 \u2013 Maximal (currently untreatable)" ], "type": "summary", "id": "623648513a8413c6530000ae", "snippets": [ { "offsetInBeginSection": 366, "offsetInEndSection": 610, "text": "The authors report on their experience with the management of multiple trauma, through the study of 617 clinical cases. Patients were evaluated with the Revised Trauma Score (RTS), Injury Severity Score (ISS) and Abbreviated Injury Scale (AIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16060187", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 318, "text": "Various trauma scoring systems were developed in order to assess injury severity and aid in decision making regarding further therapy and probable outcome.ANATOMIC INJURY SEVERITY SCALES: AIS--Abbreviated Injury Scale is a summary of all the values (from 1-9) for each organ or body part that is injured.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11320737", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "One of the more often used measures of multiple injuries is the injury severity score (ISS). Determination of the ISS is based on the abbreviated injury scale (AIS). T", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8861162", "endSection": "abstract" }, { "offsetInBeginSection": 762, "offsetInEndSection": 1019, "text": "Mortality and morbidity of patients with chest injury depend on the actual combination of multiple body systems injury. The severity of total injury can be predicted using objective scoring systems (Abbreviated Injury Scale=AIS; Injury Severity Score=ISS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29320211", "endSection": "abstract" }, { "offsetInBeginSection": 495, "offsetInEndSection": 631, "text": "The injury and trauma severity was measured using the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS), respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30624377", "endSection": "abstract" }, { "offsetInBeginSection": 14, "offsetInEndSection": 280, "text": "There is no specific injury among fatally injured frontal car-occupants in frontal car collisions, used in forensic expertise. We tried to point out the usefulness of the Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) for the expertise in such cases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17503572", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "BACKGROUND: The purpose of Abbreviated Injury Scale (AIS) is to code various types of Traumatic Brain Injuries (TBI) based on their anatomical location and severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691038", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Using Abbreviated Injury Scale (AIS) codes to classify Computed Tomography (CT) features in the Marshall System.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691038", "endSection": "title" }, { "offsetInBeginSection": 376, "offsetInEndSection": 523, "text": "The abbreviated injury scale (AIS) is the only dictionary specifically designed as a system to define the severity of injuries throughout the body.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17092503", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "Refinements in injury scaling of blunt trauma and expansion to include penetrating injuries have resulted in the publication of the 1985 revision of the Abbreviated Injury Scale (AIS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3339667", "endSection": "abstract" }, { "offsetInBeginSection": 180, "offsetInEndSection": 431, "text": "The Abbreviated Injury Scale (AIS) is a commonly used anatomical-based coding system created to classify and describe injury severity after initial presentation, once test results are able to better define the anatomical characteristics of the injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30663437", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "BACKGROUND: The Abbreviated Injury Scale (AIS) score is used widely to quantify injury severity by body region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34469860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Background: The most widely used methods of describing traumatic brain injury (TBI) are the Glasgow Coma Scale (GCS) and the Abbreviated Injury Sca", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29137197", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "BACKGROUND: Injury severity measures are based either on the Abbreviated Injury Scale (AIS) or the International Classification of dise", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20356359", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "BACKGROUND: The purpose of Abbreviated Injury Scale (AIS) is to code various types of Traumatic Brain Injuries (TBI) based on their anatomical location and ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691038", "endSection": "abstract" }, { "offsetInBeginSection": 327, "offsetInEndSection": 674, "text": "uries. Many facilities treating trauma patients perform duplicate coding for trauma diagnoses using two different classification systems, the ICD for administrative purposes and the Abbreviated Injury Scale (AIS) for trauma registry, because unambiguous conversion of codes between the ICD and AIS is not always possible due to structural differen", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29930816", "endSection": "abstract" }, { "offsetInBeginSection": 548, "offsetInEndSection": 642, "text": "8 in. on any site. The Abbreviated Injury Scale (AIS) was used to determine injury patterns fo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30841797", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "BACKGROUND: The Abbreviated Injury Scale (AIS) score is used widely to quantify injury severity by ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34469860", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "BACKGROUND: The purpose of Abbreviated Injury Scale (AIS) is to code various types of Traumatic Brain Injuries (TBI) based on their anatomical location a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20691038", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 166, "text": "sage and proven value of the Abbreviated Injury Scale (AIS) in rating severity of trauma, it is essential that certain reliability issues concerning i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3925257", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 421, "text": "universal scoring system in the field of trauma applicable in clinic and research. In engineering it is used as a classification system for vehicle safety. The AIS can therefore be considered as an international, interdisciplinary and universal code of injury severity", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20376615", "endSection": "abstract" }, { "offsetInBeginSection": 400, "offsetInEndSection": 473, "text": "The Abbreviated Injury Scale (AIS) was used to ascertain injury severity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8859913", "endSection": "abstract" }, { "offsetInBeginSection": 524, "offsetInEndSection": 648, "text": "The Abbreviated Injury Scale is a system developed in the United States for ranking the severity of specific trauma lesions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7282320", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "BACKGROUND: The Abbreviated Injury Scale (AIS), developed by the Association for the Advancement of Automotive Medicine is the most widely used anatomic injury severity scale in the world (Association for the Advancement of Automoti", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10452467", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 226, "text": "BACKGROUND: The Abbreviated Injury Scale (AIS) is an anatomical-based coding system created by the Association for the Advancement of Automotive Medicine, utilized to classify and code injuries resulting from trauma, in order ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27586096", "endSection": "abstract" } ] }, { "body": "Which protein family is epiregulin a member of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32700456" ], "ideal_answer": [ "EREG (epiregulin), a member of the epidermal growth factor (EGF) family." ], "exact_answer": [ "epidermal growth factor family" ], "type": "factoid", "id": "6237a8343a8413c6530000b2", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 225, "text": "EREG (epiregulin), a member of the epidermal growth factor (EGF) family, plays a role in inflammation, wound healing, normal physiology and malignancies. However, little is known about its function on hair growth.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32700456", "endSection": "abstract" } ] }, { "body": "Describe Cap Trap RNA-seq", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34078885" ], "ideal_answer": [ "Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly,\u2009~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Cap Trap RNA-seq is a technology which combines cap trapping and long read MinION sequencing." ], "type": "summary", "id": "6202fa3cc9dfcb9c0900002c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 1255, "text": "Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly,\u2009~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34078885", "endSection": "abstract" } ] }, { "body": "What is the use of the Canadian C-Spine Rule?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33987067", "http://www.ncbi.nlm.nih.gov/pubmed/32965634", "http://www.ncbi.nlm.nih.gov/pubmed/28844294", "http://www.ncbi.nlm.nih.gov/pubmed/32805098", "http://www.ncbi.nlm.nih.gov/pubmed/17288613", "http://www.ncbi.nlm.nih.gov/pubmed/34108196", "http://www.ncbi.nlm.nih.gov/pubmed/32348267", "http://www.ncbi.nlm.nih.gov/pubmed/34548412", "http://www.ncbi.nlm.nih.gov/pubmed/19394111", "http://www.ncbi.nlm.nih.gov/pubmed/32373348", "http://www.ncbi.nlm.nih.gov/pubmed/16730989" ], "ideal_answer": [ "The Canadian C-spine rule clinically clears cervical spine fracture without imaging." ], "type": "summary", "id": "6200879ac9dfcb9c09000021", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "PURPOSE: Although, Canadian C-spine rule and the National Emergency X-Radiography Utilization Study (NEXUS) criteria in ruling out clinically important cervical spine injuries have been validated using large prospective studies, no consensus exist as to which rule should be endorsed.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32965634", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "OBJECTIVE: The Canadian C-Spine Rule (CCR) and the National Emergency X-Radiography Utilization Study (NEXUS) criteria are two commonly used clinical decision rules which use midline cervical spine (c-spine) tenderness on palpation as an indication for c-spine imaging post-trauma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 307, "text": "BACKGROUND: A consistent approach to cervical spine injury (CSI) clearance for patients 65 and older remains a challenge. Clinical clearance algorithms like the National Emergency X-Radiography Utilisation Study (NEXUS) criteria have variable accuracy and the Canadian C-spine rule excludes older patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34108196", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 852, "text": ". Clinical decision rules such as the Canadian C-Spine Rule are frequently used to risk-stratify patients needing radiography. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33987067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Pragmatic Strategy Empowering Paramedics to Assess Low-Risk Trauma Patients With the Canadian C-Spine Rule and Selectively Transport Them Without Immobilization: Protocol for a Stepped-Wedge Cluster Randomized Trial.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32348267", "endSection": "title" }, { "offsetInBeginSection": 1174, "offsetInEndSection": 1329, "text": "The high sensitivity of the Canadian C-spine Rule (CCR) prevents missing C-spine injuries while limiting the amount of unnecessary radiologic examinations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32373348", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "The Canadian C-spine rule clinically clears cervical spine fracture without imaging.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32805098", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "OBJECTIVE: The Canadian C-Spine Rule (CCR) and the National Emergency X-Radiography Utilization Study (NEXUS) criteria are two commonly used clinical decision rules which use midline cervical spine (c-spine) tenderness on palpation as an indication for c-spine imaging post-t", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548412", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "INTRODUCTION: The Canadian C-Spine Rule (CCR) is a clinical decision aid to facilitate the safe removal of cervical collars in the alert, orientated, low-risk adult trau", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28844294", "endSection": "abstract" }, { "offsetInBeginSection": 290, "offsetInEndSection": 498, "text": "nt. The Canadian C-Spine Rule is designed to allow physicians to be more selective and accurate in ordering C-spine radiography, and to rapidly clear the C-spine without the need for radiography in many patie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17288613", "endSection": "abstract" }, { "offsetInBeginSection": 735, "offsetInEndSection": 858, "text": " decision rules such as the Canadian C-Spine Rule are frequently used to risk-stratify patients needing radiography. The le", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33987067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The Canadian c-spine rule (CCR) allows safe, reproducible use of radiography in alert, stable patients with potential c-spine injury in the emergency setting [Stiell, I., Cle", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16730989", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "The Canadian C-spine rule clinically clears cervical spine fracture without imaging", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32805098", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 490, "text": " efficient. The Canadian C-Spine Rule is designed to allow physicians to be more selective and accurate in ordering C-spine radiography, and to rapidly clear the C-spine without the need for radiography in ma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17288613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "STUDY OBJECTIVE: We designed the Canadian C-Spine Rule for the clinical clearance of the cervical spine, without need for diagnostic imaging, in alert and stable", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19394111", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "The Canadian c-spine rule (CCR) allows safe, reproducible use of radiography in alert, stable patients with potential c-spine injury in the emergency setting [Stiell, I., Clement, C., McKnight, R., Brison, R., Schull, M., Lowe, B., Worthington, J., Eisenhauer, M., Cass, D., Greenberg, G., MacPhail, I., Dreyer, J., Lee, J., Bandiera, G., Reardon, M., Holroyd, B., Lesiuk, H., G. Wells, 2003.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16730989", "endSection": "abstract" } ] }, { "body": "What is the Daughterless gene?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11731451", "http://www.ncbi.nlm.nih.gov/pubmed/8217842", "http://www.ncbi.nlm.nih.gov/pubmed/8149916" ], "ideal_answer": [ "The daughterless (da) gene in Drosophila encodes a broadly expressed transcriptional regulator whose specific functions in the control of sex determination and neurogenesis have been extensively examined." ], "exact_answer": [ "The daughterless (da) gene in Drosophila encodes a broadly expressed transcriptional regulator whose specific functions in the control of sex determination and neurogenesis have been extensively examined." ], "type": "factoid", "id": "622d1ed13a8413c6530000a3", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "As the only class I helix-loop-helix transcription factor in Drosophila, Daughterless (Da) has generally been regarded as a ubiquitously expressed binding partner for other developmentally regulated bHLH transcription factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11731451", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "The daughterless (da) gene in Drosophila encodes a broadly expressed transcriptional regulator whose specific functions in the control of sex determination and neurogenesis have been extensively examined. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8149916", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "The daughterless (da) gene in Drosophila functions in the regulation of at least three significant developmental pathways: sex determination, neurogenesis and oogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8217842", "endSection": "abstract" } ] }, { "body": "Is telomestatin, a novel statin drug used to treat high cholesterol?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/11878947", "http://www.ncbi.nlm.nih.gov/pubmed/28611443", "http://www.ncbi.nlm.nih.gov/pubmed/23909929", "http://www.ncbi.nlm.nih.gov/pubmed/16652154", "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "http://www.ncbi.nlm.nih.gov/pubmed/12917635" ], "ideal_answer": [ "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor and is used to treat cancer.", "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor." ], "exact_answer": "no", "type": "yesno", "id": "623a24d6f0baec9a1b000002", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 139, "text": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11878947", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11878947", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635", "endSection": "title" }, { "offsetInBeginSection": 149, "offsetInEndSection": 220, "text": " G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095),", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635", "endSection": "abstract" }, { "offsetInBeginSection": 380, "offsetInEndSection": 509, "text": " We found that treatment with telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 93, "text": "Telomerase inhibitor, telomestatin, a specific mechanism to interact with telomere structure", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "endSection": "title" }, { "offsetInBeginSection": 128, "offsetInEndSection": 232, "text": "Telomestatin specifically inhibited telomerase without affecting reverse transcriptases and polymerases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 379, "text": "In addition, telomestatin induced telomere shortening, but its ratio was extremely faster than that observed in physiological telomere shortening.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "endSection": "abstract" }, { "offsetInBeginSection": 384, "offsetInEndSection": 530, "text": "ructure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23909929", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28611443", "endSection": "abstract" }, { "offsetInBeginSection": 871, "offsetInEndSection": 961, "text": "Thus, telomestatin provide the novel therapeutic molecular target for cancer chemotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15283144", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16652154", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), against human leukemia cells: involvement of ATM-dependent DNA damage response pathways.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12917635", "endSection": "title" } ] }, { "body": "What is amphiregulin a ligand of?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34893673" ], "ideal_answer": [ "Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand." ], "exact_answer": [ "epidermal growth factor receptor" ], "type": "factoid", "id": "6237a8a33a8413c6530000b3", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34893673", "endSection": "abstract" } ] }, { "body": "Which genetic susceptibility loci are implicated in irritable bowel syndrome (IBS)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34741163" ], "ideal_answer": [ "There have been six genetic susceptibility loci identified and confirmed for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6.", "Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6." ], "exact_answer": [ [ "NCAM1" ], [ "CADM2" ], [ "PHF2", "FAM120A" ], [ "DOCK9" ], [ "CKAP2", "TPTE2P3" ], [ "BAG6" ] ], "type": "list", "id": "6206743ac9dfcb9c09000037", "snippets": [ { "offsetInBeginSection": 299, "offsetInEndSection": 643, "text": "We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34741163", "endSection": "abstract" } ] }, { "body": "Is there an association between Guillain\u2013Barr\u00e9 syndrome and covid vaccine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34306190", "http://www.ncbi.nlm.nih.gov/pubmed/33968610", "http://www.ncbi.nlm.nih.gov/pubmed/34330729", "http://www.ncbi.nlm.nih.gov/pubmed/34649856", "http://www.ncbi.nlm.nih.gov/pubmed/34560365", "http://www.ncbi.nlm.nih.gov/pubmed/34418708", "http://www.ncbi.nlm.nih.gov/pubmed/34648420", "http://www.ncbi.nlm.nih.gov/pubmed/34538679", "http://www.ncbi.nlm.nih.gov/pubmed/34548920", "http://www.ncbi.nlm.nih.gov/pubmed/32896460", "http://www.ncbi.nlm.nih.gov/pubmed/34187803", "http://www.ncbi.nlm.nih.gov/pubmed/34617967", "http://www.ncbi.nlm.nih.gov/pubmed/34484780" ], "ideal_answer": [ "Yes. There series reporting Guillain\u2013Barr\u00e9 syndrome after COVID-19 vaccination." ], "exact_answer": "yes", "type": "yesno", "id": "61f7d4da882a024a10000033", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "AstraZeneca COVID-19 vaccine and Guillain- Barr\u00e9 Syndrome in Tasmania: A causal link?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34560365", "endSection": "title" }, { "offsetInBeginSection": 518, "offsetInEndSection": 731, "text": "Nearly all reported cases of post-COVID-19 vacciation inflammatory demyelinating polyneuropathy are linked to AstraZeneca vaccination and a variant with bifacial weakness is the most reported form of GBS globally.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34560365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Guillain-Barr\u00e9 Syndrome Presenting as Facial Diplegia after COVID-19 Vaccination: A Case Report.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34538679", "endSection": "title" }, { "offsetInBeginSection": 489, "offsetInEndSection": 639, "text": "CASE REPORT: We report a case of atypical GBS occurring after Coronavirus disease 2019 (COVID-19) vaccination in an otherwise healthy 38-year-old man.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34538679", "endSection": "abstract" }, { "offsetInBeginSection": 1238, "offsetInEndSection": 1489, "text": "It is critical for emergency physicians to be aware of the manifold presentations of GBS for early recognition and treatment. This may be of particular importance in the context of a worldwide vaccination campaign in response to the COVID-19 pandemic.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34538679", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Guillain-Barr\u00e9 syndrome following ChAdOx1 nCoV-19 COVID-19 vaccination: A case series.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548920", "endSection": "title" }, { "offsetInBeginSection": 171, "offsetInEndSection": 326, "text": "We report three patients who developed Guillain-Barr\u00e9 syndrome following ChAdOx1 nCoV-19 vaccination, who did not have active or prior COVID-19 infection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34548920", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "We report a case of Guillain-Barr\u00e9\u00a0syndrome (GBS) following the first dose of Oxford/AstraZeneca COVID-19 vaccine with papilledema as atypical onset.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34418708", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "We report a case of Guillain-Barr\u00e9 syndrome (GBS) occurring soon after the first dose of Vaxzevria (previously known as COVID-19 vaccine AstraZeneca).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34330729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Guillain-\u200bBarr\u00e9 Syndrome Associated with COVID-19 Vaccination", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34648420", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Guillain-\u200bBarr\u00e9 Syndrome Associated with COVID-19 Vaccination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34648420", "endSection": "title" }, { "offsetInBeginSection": 135, "offsetInEndSection": 278, "text": "To date, cases of Guillain-Barr\u00e9 syndrome (GBS) following a COVID vaccine (Pfizer, Johnson & Johnson, Janssen, AstraZeneca) have been reported.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34649856", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 59, "text": "Case of Guillain-Barr\u00e9 syndrome following COVID-19 vaccine.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34187803", "endSection": "title" }, { "offsetInBeginSection": 480, "offsetInEndSection": 630, "text": "We report a case of Guillain-Barr\u00e9 syndrome after the first dose of SARS-CoV-2 vaccine and believe this is a temporal, rather than causal association.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33968610", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "COVID-19 vaccine causing Guillain-Barre syndrome, a rare potential side effect.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34484780", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Association of Receipt of the Ad26.COV2.S COVID-19 Vaccine With Presumptive Guillain-Barr\u00e9 Syndrome, February-July 2021.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34617967", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "Guillain-Barr\u00e9 syndrome associated with Covid-19: A close relationship or just a coincidence? (Review).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34306190", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Relation between COVID-19 and Guillain-Barr\u00e9 syndrome in adults. Systematic review.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32896460", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Guillain-Barr\u00e9 syndrome after COVID-19 vaccination.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34330729", "endSection": "title" } ] }, { "body": "What is the function of the protein calreticulin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33360823", "http://www.ncbi.nlm.nih.gov/pubmed/34472223", "http://www.ncbi.nlm.nih.gov/pubmed/34495528", "http://www.ncbi.nlm.nih.gov/pubmed/32733014" ], "ideal_answer": [ "Calreticulin (CALR) is an endoplasmic reticulum (ER)-resident protein involved in a spectrum of cellular processes. In healthy cells, CALR operates as a chaperone and Ca2+ buffer to assist correct protein folding within the ER." ], "exact_answer": [ "chaperone and Ca2+ buffer to assist correct protein folding within the ER" ], "type": "factoid", "id": "623dfd2ef0baec9a1b000004", "snippets": [ { "offsetInBeginSection": 718, "offsetInEndSection": 938, "text": "Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34495528", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The lectin chaperones calnexin (CNX) and calreticulin (CRT) localized in the endoplasmic reticulum play important roles in glycoprotein quality control. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33360823", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 155, "text": "Calreticulin (CRT), an endoplasmic reticulum-resident protein generally overexpressed in cancer cells, is associated with radiation resistance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34472223", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Calreticulin (CALR) is an endoplasmic reticulum (ER)-resident protein involved in a spectrum of cellular processes. In healthy cells, CALR operates as a chaperone and Ca2+ buffer to assist correct protein folding within the ER.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32733014", "endSection": "abstract" } ] }, { "body": "Atlanto-axial rotary instability (Fielding type 1) is common to what diseases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32623537", "http://www.ncbi.nlm.nih.gov/pubmed/6523080", "http://www.ncbi.nlm.nih.gov/pubmed/11301365", "http://www.ncbi.nlm.nih.gov/pubmed/2645074", "http://www.ncbi.nlm.nih.gov/pubmed/22665557", "http://www.ncbi.nlm.nih.gov/pubmed/15776322", "http://www.ncbi.nlm.nih.gov/pubmed/16272271", "http://www.ncbi.nlm.nih.gov/pubmed/2492542", "http://www.ncbi.nlm.nih.gov/pubmed/16525818", "http://www.ncbi.nlm.nih.gov/pubmed/33850389", "http://www.ncbi.nlm.nih.gov/pubmed/33763273" ], "ideal_answer": [ "Atlanto-axial instability (AAI) is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) syndromes as well as infectious disease.", "Atlanto-axial instability (AAI) is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) syndromes, where it typically presents as a rotary subluxation due to incompetence of the alar ligament." ], "exact_answer": [ [ "rheumatoid arthritis" ], [ "connective tissues disorders" ], [ "infectious disease" ], [ "Stickler syndrome" ], [ "Loeys-Dietz syndrome" ], [ "Marfan's syndrome" ], [ "Morquio syndrome" ], [ "Ehlers-Danlos (EDS) syndrome" ] ], "type": "list", "id": "6235f0e93a8413c6530000ad", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 334, "text": "Atlanto-axial instability (AAI) is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) syndromes, where it typically presents as a rotary subluxation due to incompetence of the alar ligament.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32623537", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Grisel's syndrome is a unilateral or bilateral subluxation of C1 on C2, associated with an infectious condition in the head or neck.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2645074", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 483, "text": "Compression of the spinal cord caused by atlanto-axial instability is a common, serious complication in SED patients, and causes severe spinal cord symptoms or occasionally sudden death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301365", "endSection": "abstract" }, { "offsetInBeginSection": 484, "offsetInEndSection": 645, "text": "We present an SED patient who underwent a posterior fusion of the occiput to the cervical spine for severe spinal cord symptoms due to atlanto-axial instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301365", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 256, "text": "Atlantoaxial rotatory fixation (AARF) resulting from drug-induced cervical dystonia (DICD) represents an extremely rare complication of antipsychotic treatment, requiring a comprehensive assessment of pharmacologic therapy and timely radiologic workup. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33763273", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "A relatively rare report of an 8-year-old girl with Maroteaux-Lamy syndrome that is Type VI mucopolysaccharidosis who presented with symptoms of spastic quadriparesis related to atlantoaxial instability is presented", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33850389", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "We report a 15-year-old boy with mucopolysaccharidosis (MPS) Type VII (Sly disease) who was found to have atlantoaxial instability with quadriparesis. Su", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2492542", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "Atlanto-axial rotatory fixation (AARF) is a rare cause of childhood torticollis that may occur spontaneously or in association with trauma and upper respiratory infections.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15776322", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Ankylosing spondylitis is one of the commonest inflammatory diseases of the axial skeleton and can be complicated by atlanto-axial instability.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22665557", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Atlantoaxial instability (AAI) affects 10-20% of individuals with Down syndrome (DS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16525818", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Atlanto-axial subluxation in rheumatoid arthritis. A study of 104 hospital patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6523080", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 214, "text": "The cervical spine often becomes involved early in the course of rheumatoid arthritis, leading to three different patterns of instability: atlantoaxial subluxation, atlantoaxial impaction, and subaxial subluxation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16272271", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Arthritic affection of the upper cervical spine is relatively common in rheumatoid arthritis (RA). Atlanto-axial subluxations are also reported to occur frequently,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6523080", "endSection": "abstract" } ] }, { "body": "What is the effect of epiregulin on leptin secretion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30400011" ], "ideal_answer": [ "Epiregulin induces leptin secretion." ], "exact_answer": [ "induction", "increase" ], "type": "factoid", "id": "6237ab873a8413c6530000b6", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "Epiregulin induces leptin secretion and energy expenditure in high-fat diet-fed mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30400011", "endSection": "title" }, { "offsetInBeginSection": 723, "offsetInEndSection": 845, "text": " EREG increased leptin production and secretion in a dose-dependent manner in iAb fat explants via the EGFR/MAPK pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30400011", "endSection": "abstract" }, { "offsetInBeginSection": 1522, "offsetInEndSection": 1633, "text": "Our data revealed a new role of EREG in induction of leptin secretion leading to the energy expenditure state. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30400011", "endSection": "abstract" } ] }, { "body": "Which JASPAR release is JASPAR 2022?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34850907" ], "ideal_answer": [ "JASPAR (http://jaspar.genereg.net/) is an open-access database containing manually curated, non-redundant transcription factor (TF) binding profiles for TFs across six taxonomic groups. In JASPAR 2022, JASPAR's 9th release, the CORE collection was expanded with 341 new profiles (148 for plants, 101 for vertebrates, 85 for urochordates, and 7 for insects), which corresponds to a 19% expansion over the previous release." ], "exact_answer": [ "9th" ], "type": "factoid", "id": "6202f600c9dfcb9c0900002b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34850907", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 1313, "text": "JASPAR (http://jaspar.genereg.net/) is an open-access database containing manually curated, non-redundant transcription factor (TF) binding profiles for TFs across six taxonomic groups. In this 9th release, we expanded the CORE collection with 341 new profiles (148 for plants, 101 for vertebrates, 85 for urochordates, and 7 for insects), which corresponds to a 19% expansion over the previous release. We added 298 new profiles to the Unvalidated collection when no orthogonal evidence was found in the literature. All the profiles were clustered to provide familial binding profiles for each taxonomic group. Moreover, we revised the structural classification of DNA binding domains to consider plant-specific TFs. This release introduces word clouds to represent the scientific knowledge associated with each TF. We updated the genome tracks of TFBSs predicted with JASPAR profiles in eight organisms; the human and mouse TFBS predictions can be visualized as native tracks in the UCSC Genome Browser. Finally, we provide a new tool to perform JASPAR TFBS enrichment analysis in user-provided genomic regions. All the data is accessible through the JASPAR website, its associated RESTful API, the R/Bioconductor data package, and a new Python package, pyJASPAR, that facilitates serverless access to the data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34850907", "endSection": "abstract" } ] }, { "body": "Is Erythropoietin effective for neuroprotection of Preterm Infants.", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32961562", "http://www.ncbi.nlm.nih.gov/pubmed/31940698", "http://www.ncbi.nlm.nih.gov/pubmed/34030616" ], "ideal_answer": [ "No. High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age." ], "exact_answer": "no", "type": "yesno", "id": "61fa904fc9dfcb9c09000004", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31940698", "endSection": "abstract" }, { "offsetInBeginSection": 1448, "offsetInEndSection": 2232, "text": "There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P\u2009=\u20090.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31940698", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1054, "text": "Based on existing evidence, it is still too early to recommend Epo as the standard treatment for preterm brain injury.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34030616", "endSection": "abstract" }, { "offsetInBeginSection": 816, "offsetInEndSection": 1066, "text": "Erythropoietin treatment of preterm infants did not result in neuroprotection at 2 years of age in two out of three published large randomized controlled trials; however, long-term follow-up of these infants is needed to come to definite conclusions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32961562", "endSection": "abstract" } ] }, { "body": "What is the SPRTN protein function?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33348378", "http://www.ncbi.nlm.nih.gov/pubmed/33183910", "http://www.ncbi.nlm.nih.gov/pubmed/34551432", "http://www.ncbi.nlm.nih.gov/pubmed/34189469" ], "ideal_answer": [ "The protease SPRTN emerged as the essential enzyme for DNA-protein crosslink proteolysis repair." ], "exact_answer": [ "DNA-protein crosslink proteolysis repair" ], "type": "factoid", "id": "622deabc3a8413c6530000a6", "snippets": [ { "offsetInBeginSection": 384, "offsetInEndSection": 512, "text": "we explored the role of Spartan (SPRTN), a metalloprotease associated with DNA replication, which removes proteins forming DPCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34551432", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Repair of covalent DNA-protein crosslinks (DPCs) by the metalloprotease SPRTN prevents genome instability, premature aging and carcinogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33348378", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The protease SPRTN emerged as the essential enzyme for DNA-protein crosslink proteolysis repair", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33183910", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Covalent DNA-protein crosslinks (DPCs) have emerged as pervasive sources of genome instability. DPCs are targeted for repair by DNA-dependent proteases of the Wss1/SPRTN family.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34189469", "endSection": "abstract" } ] }, { "body": "What part of the body is associated with Cauda equina", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/26442520", "http://www.ncbi.nlm.nih.gov/pubmed/25495513", "http://www.ncbi.nlm.nih.gov/pubmed/22254963", "http://www.ncbi.nlm.nih.gov/pubmed/27753733", "http://www.ncbi.nlm.nih.gov/pubmed/3356808", "http://www.ncbi.nlm.nih.gov/pubmed/22996855", "http://www.ncbi.nlm.nih.gov/pubmed/3806684", "http://www.ncbi.nlm.nih.gov/pubmed/32541159", "http://www.ncbi.nlm.nih.gov/pubmed/33261250", "http://www.ncbi.nlm.nih.gov/pubmed/23101243", "http://www.ncbi.nlm.nih.gov/pubmed/11311464", "http://www.ncbi.nlm.nih.gov/pubmed/18664636", "http://www.ncbi.nlm.nih.gov/pubmed/10797973", "http://www.ncbi.nlm.nih.gov/pubmed/34321945", "http://www.ncbi.nlm.nih.gov/pubmed/22764663" ], "ideal_answer": [ "The cauda equina is the sack of nerve roots (nerves that leave the spinal cord between spaces in the bones of the spine to connect to other parts of the body) at the lower end of the spinal cord." ], "exact_answer": [ "spine" ], "type": "factoid", "id": "6238a0033a8413c6530000b8", "snippets": [ { "offsetInBeginSection": 218, "offsetInEndSection": 346, "text": "the right pedicle of L4, moved inside the vertebral canal (bridging the cauda equina) stopping just in front of the body of S2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33261250", "endSection": "abstract" }, { "offsetInBeginSection": 1, "offsetInEndSection": 124, "text": "Thermoesthesia-and-algesthesia status in the dermatomes of cauda equina roots in patients with lumbar spine osteochondrosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101243", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "Thermoesthesia-and-algesthesia disorders have been registered in the dermatomes of cauda equina roots of patients with lumbar spine osteochondrosis in all the cases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101243", "endSection": "abstract" }, { "offsetInBeginSection": 581, "offsetInEndSection": 722, "text": " Magnetic resonance images of the lumbar spine showed an intradural cystic lesion displacing and compressing the lower cord and cauda equina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22764663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Cauda equina syndrome is a well described state of neurologic compromise due to lumbosacral root compression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22996855", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "Acute cauda equina syndrome secondary to a lumbar synovial cyst", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22996855", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "INTRODUCTION: Schwannoma is a relatively common benign spinal cord and/or cauda equina tumor; however, giant cauda equina schwannoma with extensive scalloping of the lumbar vertebral body is a rare pathology, and the treatment strategy, including the use of surgical procedures, is controversial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495513", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 509, "text": "In this report, we present a rare case of a giant lumbar schwannoma of the cauda equina with extremely large scalloping of the vertebral body, and we discuss the surgical strategy we used to treat this pathology.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495513", "endSection": "abstract" }, { "offsetInBeginSection": 532, "offsetInEndSection": 791, "text": "In contrast, the caudal cord of Rana is reduced to a filum terminale consisting of little more than an ependymal tube; spinal nerves to all caudal myotomes leave the cord in the sacral region and reach their motor targets via a cauda equina and caudal plexus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3356808", "endSection": "abstract" }, { "offsetInBeginSection": 662, "offsetInEndSection": 791, "text": "The spinal cords of other teleosts, the sun-fish and angler, also are abbreviated and possess a filum terminale and cauda equina.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3806684", "endSection": "abstract" }, { "offsetInBeginSection": 993, "offsetInEndSection": 1126, "text": "Penetrating spinal cord injury with foreign body included or myelography stop or showing cauda equina syndrome should be operated on.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10797973", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Cauda Equina Conduction Time Determined by F-Waves in Normal Subjects and Patients With Neurogenic Intermittent Claudication Caused by Lumbar Spinal Stenosis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27753733", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "After spinal cord injury, electrical stimulation of the roots inside the spinal column at the level of the cauda equina is a safe and effective way to regain some degree of control over lower body function, e.g. bladder and bowel management and leg movement. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22254963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Malignant spinal cord compression(MSCC)is defined as a compression of the spinal cord or cauda equina with neuropathy caused by tumor spreading to the vertebral body. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32541159", "endSection": "abstract" }, { "offsetInBeginSection": 37, "offsetInEndSection": 187, "text": "nction of the cauda equina, the collection of ventral and dorsal lumbar, sacral and coccygeal nerve roots that surround the filum terminale. This most", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26442520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 295, "text": "INTRODUCTION: Schwannoma is a relatively common benign spinal cord and/or cauda equina tumor; however, giant cauda equina schwannoma with extensive scalloping of the lumbar vertebral body is a rare pathology, and the treatment strategy, including the use of surgical procedures, is controversial", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25495513", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "Cauda equina syndrome is a relatively uncommon condition typically associated with a large, space-occupying lesion within the canal of the lumbosacral spine.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18664636", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "Cauda equina syndrome refers to dysfunction of the cauda equina, the collection of ventral and dorsal lumbar, sacral and coccygeal nerve roots that surround the filum terminale.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26442520", "endSection": "abstract" }, { "offsetInBeginSection": 1320, "offsetInEndSection": 1510, "text": "The involvement of intrinsic spinal cord neurons in the compression-induced cauda equina syndrome includes anterograde, retrograde and transneuronal degeneration in the lumbosacral segments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11311464", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Single or double-level compression of the lumbosacral nerve roots located in the dural sac results in a polyradicular symptomatology clinically diagnosed as cauda equina syndrome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11311464", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 470, "text": "The cauda equina is an anatomic structure located in the lower part of the spinal canal consisting of multiple lumbar and sacral nerve roots.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34321945", "endSection": "abstract" } ] }, { "body": "What does RUNX1T1 stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32589708" ], "ideal_answer": [ "RUNX1T1 stands for runt-related transcription factor 1." ], "exact_answer": [ "runt-related transcription factor 1" ], "type": "factoid", "id": "62265b4a3a8413c653000083", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 96, "text": "Runt-related transcription factor 1 (RUNX1T1) isoforms are involved in adipogenesis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32589708", "endSection": "abstract" } ] }, { "body": "Describe InteractiveComplexHeatmap", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34864868" ], "ideal_answer": [ "InteractiveComplexHeatmap is designed with an easy-to-use interface where static complex heatmaps can be directly exported to an interactive Shiny web application only with one additional line of code.", "InteractiveComplexHeatmap is an R package that brings interactivity to the widely used ComplexHeatmap package. InteractiveComplexHeatmap is designed with an easy-to-use interface where static complex heatmaps can be directly exported to an interactive Shiny web application only with one additional line of code. InteractiveComplexHeatmap also provides flexible functionalities for integrating interactive heatmap widgets to build more complex and customized Shiny web applications." ], "type": "summary", "id": "621e5dcf3a8413c65300004f", "snippets": [ { "offsetInBeginSection": 134, "offsetInEndSection": 643, "text": "In this work, we introduce a new R package InteractiveComplexHeatmap that brings interactivity to the widely used ComplexHeatmap package. InteractiveComplexHeatmap is designed with an easy-to-use interface where static complex heatmaps can be directly exported to an interactive Shiny web application only with one additional line of code. InteractiveComplexHeatmap also provides flexible functionalities for integrating interactive heatmap widgets to build more complex and customized Shiny web applications.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864868", "endSection": "abstract" } ] }, { "body": "What is the use of Brain Metastasis Velocity (BMV) Model?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31526671", "http://www.ncbi.nlm.nih.gov/pubmed/33817641", "http://www.ncbi.nlm.nih.gov/pubmed/34775780", "http://www.ncbi.nlm.nih.gov/pubmed/29740743", "http://www.ncbi.nlm.nih.gov/pubmed/30524969", "http://www.ncbi.nlm.nih.gov/pubmed/29464141", "http://www.ncbi.nlm.nih.gov/pubmed/28586952" ], "ideal_answer": [ "Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery." ], "type": "summary", "id": "620086aac9dfcb9c09000020", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "PURPOSE/OBJECTIVE(S): Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29740743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Background: Brain metastasis velocity (BMV) predicts outcomes after initial distant brain failure (DBF) following upfront stereotactic radiosurgery (SRS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33817641", "endSection": "abstract" }, { "offsetInBeginSection": 787, "offsetInEndSection": 972, "text": "lso tells the history of the derivation and validation of BMV, a recently identified biomarker for survival and neurologic death in the brain metastasis population treated with SRS.CONC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34775780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "OBJECTIVE: To provide a review of the current status of predictive nomograms and brain metastasis velocity (BMV) in the prognostication of brain metastasis outcomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34775780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31526671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Background: Brain metastasis velocity (BMV) predicts outcomes after initial distant brain failure (DBF) following upfront stereotactic radiosurgery (SRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33817641", "endSection": "abstract" }, { "offsetInBeginSection": 248, "offsetInEndSection": 398, "text": "We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28586952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "PURPOSE/OBJECTIVE(S): Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29740743", "endSection": "abstract" }, { "offsetInBeginSection": 245, "offsetInEndSection": 397, "text": "e. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28586952", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radios", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31526671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "OBJECTIVE: To provide a review of the current status of predictive nomograms and brain metastasis velocity (BMV) in the prognostication of brain metastasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34775780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "PURPOSE/OBJECTIVE(S): Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29740743", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 351, "text": "SRS). We developed an integrated model of clinical predictors and pre-SRS MRI-derived radiomic scores (R-scores) to identify high-BMV (BMV-H) patients upon initial identification of brain metastases (BM", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33817641", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "PURPOSE/OBJECTIVE(S): Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotact", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29740743", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radio", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31526671", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Background: Brain metastasis velocity (BMV) predicts outcomes after initial distant brain failure (DBF) following upfront stereotactic radiosu", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33817641", "endSection": "abstract" }, { "offsetInBeginSection": 810, "offsetInEndSection": 1001, "text": "Besides clinical and treatment related factors, brain metastasis velocity (BMV) as a newly described clinical prognostic metric was included and calculated between first and second treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30524969", "endSection": "abstract" }, { "offsetInBeginSection": 387, "offsetInEndSection": 537, "text": "stasis velocity (vBMV) was defined as the volume of new intracranial disease at the time of distant brain failure (DBF) for the first DBF (DBF1) and s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29464141", "endSection": "abstract" } ] }, { "body": "What is \"cell competition\"?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34500336", "http://www.ncbi.nlm.nih.gov/pubmed/33508854", "http://www.ncbi.nlm.nih.gov/pubmed/34485872", "http://www.ncbi.nlm.nih.gov/pubmed/33357449" ], "ideal_answer": [ "Cell competition is a social cellular phenomenon in which unfit cells are selectively eliminated to maintain tissue homeostasis.\nAt the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer." ], "type": "summary", "id": "622df6663a8413c6530000a7", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 329, "text": "Cell competition involves a conserved fitness-sensing process during which fitter cells eliminate neighbouring less-fit but viable cells1. Cell competition has been proposed as a surveillance mechanism to ensure normal development and tissue homeostasis, and has also been suggested to act as a barrier to interspecies chimerism2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33508854", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Cell competition is a social cellular phenomenon in which unfit cells are selectively eliminated to maintain tissue homeostasis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33357449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 220, "text": "At the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34485872", "endSection": "abstract" }, { "offsetInBeginSection": 209, "offsetInEndSection": 355, "text": "Cell competition represents one of the operating arms of such quality control mechanisms and relies on fitness comparison among individual cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34500336", "endSection": "abstract" } ] }, { "body": "What is IDD in relation to organ transplantation?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28027062", "http://www.ncbi.nlm.nih.gov/pubmed/32633023", "http://www.ncbi.nlm.nih.gov/pubmed/28030433" ], "ideal_answer": [ "Imminent death donation (IDD) has been proposed as a separate category of organ donation: distinct from living donation and donation after cardiac death", "Imminent death donation (IDD) is a proposal to procure organs from patients prior to the withdrawal of life support, which is anticipated to lead to death", "Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient." ], "type": "summary", "id": "623648723a8413c6530000af", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32633023", "endSection": "abstract" }, { "offsetInBeginSection": 19, "offsetInEndSection": 173, "text": "Imminent death donation (IDD) is a proposal to procure organs from patients prior to the withdrawal of life support, which is anticipated to lead to death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28030433", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 358, "text": "Imminent death donation (IDD) has been proposed as a separate category of organ donation: distinct from living donation and donation after cardiac death", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28027062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32633023", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32633023", "endSection": "abstract" }, { "offsetInBeginSection": 190, "offsetInEndSection": 345, "text": " organ discard. Imminent death donation (IDD) has been proposed as a separate category of organ donation: distinct from living donation and donation after ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28027062", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 157, "text": "PURPOSE OF REVIEW: Imminent death donation (IDD) is a proposal to procure organs from patients prior to the withdrawal of life support, which is anticipated ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28030433", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 340, "text": "ent organ discard. Imminent death donation (IDD) has been proposed as a separate category of organ donation: distinct from living donation and donation a", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28027062", "endSection": "abstract" }, { "offsetInBeginSection": 17, "offsetInEndSection": 167, "text": ": Imminent death donation (IDD) is a proposal to procure organs from patients prior to the withdrawal of life support, which is anticipated to lead to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28030433", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "PURPOSE OF REVIEW: Imminent death donation (IDD) is a proposal to procure organs from patients prior to the withdrawal of life support, which is anticipate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28030433", "endSection": "abstract" }, { "offsetInBeginSection": 187, "offsetInEndSection": 437, "text": "ent organ discard. Imminent death donation (IDD) has been proposed as a separate category of organ donation: distinct from living donation and donation after cardiac death.RECENT FINDINGS: A protocol for IDD was developed at Rhode Island Hospital and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28027062", "endSection": "abstract" } ] }, { "body": "Is METTL3 an m6A writer, reader or eraser?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34535671" ], "ideal_answer": [ "The methyltransferase METTL3 is an m6A writer." ], "exact_answer": [ "Writer" ], "type": "factoid", "id": "62265c953a8413c653000084", "snippets": [ { "offsetInBeginSection": 200, "offsetInEndSection": 401, "text": "Here we report decreased expression of the m6A \"writer\" METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein\u00a0expression levels of METTL3 and effector molecules in NK cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34535671", "endSection": "abstract" } ] }, { "body": "What is the 4D nucleome project?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28905911" ], "ideal_answer": [ "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.", "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions.", "The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions." ], "type": "summary", "id": "6201a06fc9dfcb9c09000026", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 692, "text": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905911", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 245, "text": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28905911", "endSection": "abstract" } ] }, { "body": "Which drugs were included in the polypill that was tested in TIPS-3 trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30342297" ], "ideal_answer": [ "Polypill tested in the TIPS-3 trial was comprised of atenolol, ramipril, hydrochlorothiazide, and a statin." ], "exact_answer": [ [ "atenolol" ], [ "ramipril" ], [ "hydrochlorothiazide" ], [ "statin" ] ], "type": "list", "id": "61f7d017882a024a1000002f", "snippets": [ { "offsetInBeginSection": 467, "offsetInEndSection": 856, "text": "METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30342297", "endSection": "abstract" } ] }, { "body": "What is the drug gantenerumab targeting?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33336218", "http://www.ncbi.nlm.nih.gov/pubmed/34198582", "http://www.ncbi.nlm.nih.gov/pubmed/34155411" ], "ideal_answer": [ "Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain." ], "exact_answer": [ "Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain." ], "type": "factoid", "id": "622dfb133a8413c6530000a8", "snippets": [ { "offsetInBeginSection": 1026, "offsetInEndSection": 1183, "text": "Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34155411", "endSection": "abstract" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1327, "text": "The late-stage agents with positive clinical or biomarker data include four antibodies that engage A\u03b2 oligomers (aducanumab, lecanemab, gantenerumab, and donanemab) and ALZ-801, an oral agent that fully blocks the formation of A\u03b2 oligomers at the clinical dose.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34198582", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 136, "text": "Reduction in Amyloid Burden with Subcutaneous Gantenerumab.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336218", "endSection": "title" }, { "offsetInBeginSection": 770, "offsetInEndSection": 929, "text": "These results demonstrate that prolonged gantenerumab treatment, at doses up to 1200 mg, reduces amyloid plaque levels below the amyloid positivity threshold. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33336218", "endSection": "abstract" } ] }, { "body": "Is Ameloblastoma (AB) a common benign tumor occurring in the brain?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/28187692", "http://www.ncbi.nlm.nih.gov/pubmed/32659412", "http://www.ncbi.nlm.nih.gov/pubmed/34599642", "http://www.ncbi.nlm.nih.gov/pubmed/25206141", "http://www.ncbi.nlm.nih.gov/pubmed/34508164", "http://www.ncbi.nlm.nih.gov/pubmed/10895162", "http://www.ncbi.nlm.nih.gov/pubmed/30126803", "http://www.ncbi.nlm.nih.gov/pubmed/28191811", "http://www.ncbi.nlm.nih.gov/pubmed/32698263", "http://www.ncbi.nlm.nih.gov/pubmed/23986011", "http://www.ncbi.nlm.nih.gov/pubmed/25567699", "http://www.ncbi.nlm.nih.gov/pubmed/29274152", "http://www.ncbi.nlm.nih.gov/pubmed/34510060", "http://www.ncbi.nlm.nih.gov/pubmed/27099699", "http://www.ncbi.nlm.nih.gov/pubmed/19995435", "http://www.ncbi.nlm.nih.gov/pubmed/30420932", "http://www.ncbi.nlm.nih.gov/pubmed/34594553", "http://www.ncbi.nlm.nih.gov/pubmed/26925653", "http://www.ncbi.nlm.nih.gov/pubmed/31990904", "http://www.ncbi.nlm.nih.gov/pubmed/25298718", "http://www.ncbi.nlm.nih.gov/pubmed/31674718", "http://www.ncbi.nlm.nih.gov/pubmed/26015700", "http://www.ncbi.nlm.nih.gov/pubmed/17170964", "http://www.ncbi.nlm.nih.gov/pubmed/1569364", "http://www.ncbi.nlm.nih.gov/pubmed/30196986", "http://www.ncbi.nlm.nih.gov/pubmed/32484411", "http://www.ncbi.nlm.nih.gov/pubmed/20051072", "http://www.ncbi.nlm.nih.gov/pubmed/14970780", "http://www.ncbi.nlm.nih.gov/pubmed/27721617", "http://www.ncbi.nlm.nih.gov/pubmed/28212886", "http://www.ncbi.nlm.nih.gov/pubmed/26261564", "http://www.ncbi.nlm.nih.gov/pubmed/33394372", "http://www.ncbi.nlm.nih.gov/pubmed/21371124", "http://www.ncbi.nlm.nih.gov/pubmed/21717310", "http://www.ncbi.nlm.nih.gov/pubmed/34511355", "http://www.ncbi.nlm.nih.gov/pubmed/27435007", "http://www.ncbi.nlm.nih.gov/pubmed/21968082", "http://www.ncbi.nlm.nih.gov/pubmed/29747056" ], "ideal_answer": [ "Ameloblastoma (AM) is a slow growing and aggressive benign tumor with an odontogenic epithelial origin arising from the mandible or maxilla.", "Ameloblastoma is a neoplasm arising in the craniofacial skeleton.", "Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the mandible" ], "exact_answer": "no", "type": "yesno", "id": "6226317a3a8413c653000080", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Ameloblastoma is a benign odontogenic tumor which undergoes malignant transformation to ameloblastic carcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32659412", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 86, "text": "Ameloblastomas are benign tumors that most commonly affecting the mandible. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34510060", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 65, "text": "Ameloblastoma is a neoplasm arising in the craniofacial skeleton.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599642", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Ameloblastoma is an invasive odontogenic tumor, and for reconstruction, i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34594553", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Ameloblastoma is a locally aggressive, benign epithelial odontogenic neoplasm currently classified to include conventional, unicystic, and extraosseous/peripheral subtypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34511355", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Ameloblastoma (AM) is a slow growing and aggressive benign tumor with an odontogenic epithelial origin arising from the mandible or maxilla.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32484411", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "The ameloblastoma is a benign but aggressive neoplasm of odontogenic origin.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25206141", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "Ameloblastoma is a rare odontogenic tumor of the jaw.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28191811", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Ameloblastoma is the most common epithelial odontogenic tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26925653", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Ameloblastoma or adamantinoma is the rarest of the three forms of tumor of the odontogenic type.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25298718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "Ameloblastoma is a benign locally invasive odontogenic tumor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32698263", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Ameloblastoma is the second most common benign epithelial odontogenic tumor and though it is of a benign nature, it is locally invasive, has a high recurrence rate and could potentially become malignant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27721617", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Ameloblastoma is the most common odontogenic tumor of epithelial origin, and though it is of a benign nature, it frequently infiltrates the bone, has a high rate of recurrence and could potentially become malignant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23986011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 172, "text": "OBJECTIVES: Ameloblastoma is a benign, slow-growing, locally invasive epithelial tumor of odontogenic origin, with unlimited growth capacity and a strong tendency to recur.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30126803", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "Ameloblastoma, a benign but locally aggressive odontogenic tumor, often demonstrates metastasis despite benign histological features and this variant is termed as metastasizing ameloblastoma (METAM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33394372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31674718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-fac", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Peripheral ameloblastoma is a benign odontogenic tumor with the same histological characteristics as the centrally located ameloblastoma, but appearing in the gingiva and mucosa of the tooth-bearing area of the jaws.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1569364", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "BACKGROUND Ameloblastoma (AB) is a common odontogenic epithelial tumor, with locally invasive behavior and high recurrence.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31990904", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Ameloblastoma(AB) is an aggressive and slow-growing tumor with high recurrence rate, which arises from odontogenic epithelium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30196986", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the jawbone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34508164", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 351, "text": "or growth. Ameloblastoma (AB) is a relatively common odontogenic epithelial neoplasm that manifests local infiltrative intraosse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14970780", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31674718", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 236, "text": "Ameloblastoma is a benign epithelial odontogenic tumor that typically arises in the mandible or maxilla or, rarely, in the immediate adjacent soft tissues", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25567699", "endSection": "abstract" }, { "offsetInBeginSection": 79, "offsetInEndSection": 229, "text": "nic epithelial components with a mature fibrous stroma. It is the second most common odontogenic neoplasm following odontome. Acanthomatous ameloblast", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30420932", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "OBJECTIVE AND IMPORTANCE: Ameloblastoma is a locally aggressive benign tumor, commonly occurring in the mandible", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28187692", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "BACKGROUND AND OVERVIEW: Ameloblastoma is an odontogenic tumor predominantly occurring in patients who are in their 20s and 30s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27435007", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 193, "text": "BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261564", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "BACKGROUND: Ameloblastoma is a neoplasm classified as a benign epithelial odontogenic tumor of the jaws, grow slowly and are locally invasive", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29274152", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "BACKGROUND: Ameloblastoma is a frequent odontogenic benign tumor characterized by local invasiveness, high risk of recurrence and occasional metastasis and malignant transformation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19995435", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "BACKGROUND: Ameloblastoma is a rare benign odontogenic tumor with locally aggressive behavior and a high recurrence rate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21968082", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "BACKGROUND: Ameloblastoma is a benign odontogenic tumor, exhibiting local invasiveness and high rate of recurrence", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21371124", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 653, "text": "BACKGROUND: Ameloblastoma is a rare benign odontogenic tumor with a metastasis rate estimated at 2% of cases, mainly involving the lung (80%) and lymph nodes (20%).METHODS: We hereby present the case of a 26 year old patient with a history of locally recurrent mandibular ameloblastoma who developed a temporal intracranial ameloblastoma tumor requiring a collaborative neurosurgical and maxillo-facial radical surgical approach.CONCLUSION: Although ameloblastomas are histologically benign, the temporal topography questions the dissemination pathophysiology of the tumor (metastasis or local extension through temporal muscle fibers), mainly relevant ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29747056", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Ameloblastoma is a histologically benign tumor derived from odontogenic apparatus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10895162", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "BACKGROUND: Ameloblastoma is a benign odontogenic tumour that may exhibit aggressive biological behaviour with local recurrence and metastasis following initial surgica", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27099699", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Ameloblastomas are histologically benign tumors derived from the odontogenic apparatus.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17170964", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "Ameloblastoma is a benign odontogenic tumor generally present in the jaw bone.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26015700", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Ameloblastoma is a locally aggressive tumor derived from odontogenic epithelium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28212886", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Ameloblastoma is the most common clinically significant epithelial odontogenic tumor, and is considered a benign but locally aggressive tumor of the craniofacial region.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20051072", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Ameloblastoma (AB), which is the most common odontogenic tumor, may originate from the dental lamina remnants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21717310", "endSection": "abstract" } ] }, { "body": "In which aspects of the immune response is m6A methylation implicated?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34515345" ], "ideal_answer": [ "m6A is a novel regulator of immune system homeostasis and activation. m6A modifications and m6A modifying proteins play a critical role in pathogen recognition, immune cell activation, immune cell fate decisions, and immune reactions. These modifications modulate the fate decisions of innate and adaptive immune cells and regulate immune responses in immune-associated diseases, including viral infections and cancer." ], "exact_answer": [ [ "pathogen recognition" ], [ "immune cell activation" ], [ "immune cell fate decisions" ], [ "immune reactions" ] ], "type": "list", "id": "622664fa3a8413c653000086", "snippets": [ { "offsetInBeginSection": 400, "offsetInEndSection": 932, "text": "Here, we summarize the current state of m6 A methylation researches, focusing on how these modifications modulate the fate decisions of innate and adaptive immune cells and regulate immune responses in immune-associated diseases, including viral infections and cancer. These studies showed that m6 A modifications and m6 A modifying proteins play a critical role in pathogen recognition, immune cell activation, immune cell fate decisions, and immune reactions. m6 A is a novel regulator of immune system homeostasis and activation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34515345", "endSection": "abstract" } ] }, { "body": "Describe nextNEOpi", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34788790" ], "ideal_answer": [ "NextNEOpi is a comprehensive and fully-automated bioinformatic pipeline to predict tumor neoantigens from raw DNA and RNA sequencing data. In addition, nextNEOpi quantifies neoepitope- and patient-specific features associated with tumor immunogenicity and response to immunotherapy." ], "type": "summary", "id": "621e991a3a8413c653000052", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 76, "text": "nextNEOpi: a comprehensive pipeline for computational neoantigen prediction.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788790", "endSection": "title" }, { "offsetInBeginSection": 451, "offsetInEndSection": 748, "text": "Here, we present nextNEOpi, a comprehensive and fully-automated bioinformatic pipeline to predict tumor neoantigens from raw DNA and RNA sequencing data. In addition, nextNEOpi quantifies neoepitope- and patient-specific features associated with tumor immunogenicity and response to immunotherapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788790", "endSection": "abstract" } ] }, { "body": "What is the use of the ATRIA score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31800901", "http://www.ncbi.nlm.nih.gov/pubmed/29030869", "http://www.ncbi.nlm.nih.gov/pubmed/28363682", "http://www.ncbi.nlm.nih.gov/pubmed/24991318", "http://www.ncbi.nlm.nih.gov/pubmed/29274754", "http://www.ncbi.nlm.nih.gov/pubmed/29560065", "http://www.ncbi.nlm.nih.gov/pubmed/33550837" ], "ideal_answer": [ "ATRIA score determines bleeding risk for patients on warfarin." ], "type": "summary", "id": "62008577c9dfcb9c0900001f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 296, "text": "Many parameters included in the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) and CHA2DS2-VASc (congestive heart failure, hypertension, age \u226575 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex category) scores also predict coronary artery disease (CAD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33550837", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "The HAS-BLED, ATRIA, and ORBIT Bleeding Scores in Atrial Fibrillation Patients Using Non-Vitamin K Antagonist Oral Anticoagulants.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29274754", "endSection": "title" }, { "offsetInBeginSection": 259, "offsetInEndSection": 932, "text": "METHODS: Using the Danish registries, we evaluated and compared the risk classification properties of the Hypertension, Age, Stroke, Bleeding tendency/predisposition, Labile international normalized ratios, Elderly age/frailty, Drugs such as concomitant aspirin/nonsteroidal anti-inflammatory drugs or alcohol excess (HAS-BLED), Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA), and Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) scores for predicting major bleeding in 57,930 atrial fibrillation patients (44.6% female; mean age 73.5 years, standard deviation 11.4 years; mean CHA2DS2-VASc score 3.2, standard deviation 1.8).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29274754", "endSection": "abstract" }, { "offsetInBeginSection": 1608, "offsetInEndSection": 1900, "text": "All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR2 HAGES (C-statistic\u00a0=\u00a00.71, 95% CI 0.60-0.82, P\u00a0<\u00a0.001) and ATRIA score (C-statistic\u00a0=\u00a00.70, 95% CI 0.58-0.82, P\u00a0<\u00a0.001) show acceptable discrimination performance for major bleeding events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29030869", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 923, "text": "Patients were then sorted into two groups at non-low and low risk of bleeding, as defined by an ATRIA score >3 and \u22643 respectively, and compared regarding major adverse cardiac and vascular events (MACVE) and bleeding.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28363682", "endSection": "abstract" }, { "offsetInBeginSection": 309, "offsetInEndSection": 544, "text": "Methods: This prospective study included non-anticoagulated adults at high risk for ischemic stroke (ATRIA score \u22657) who received emergency AF/FL care and were discharged home from seven community EDs between May 2011 and August 2012. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29560065", "endSection": "abstract" }, { "offsetInBeginSection": 773, "offsetInEndSection": 1089, "text": "viduals with moderate-to-high stroke risk per CHADS2 but not at high bleeding risk per ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score were evaluated for warfarin use, as identified by the presence of \u22651 warfarin prescription claims within 12 months after the index diagnosis. War", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991318", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "BACKGROUND: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) risk score used to detect the thromboembolic and hemorrhagic risk in atrial fibrillation patients has been shown recently to predict poor clinical outcomes in patients with acute myocardial infarction (ACS), regardless of having atrial fibrillat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31800901", "endSection": "abstract" } ] }, { "body": "Which protein is targeted by Herceptin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33468562", "http://www.ncbi.nlm.nih.gov/pubmed/34532642" ], "ideal_answer": [ "Her2 is targeted by Herceptin." ], "exact_answer": [ "Her2" ], "type": "factoid", "id": "622b99f73a8413c653000093", "snippets": [ { "offsetInBeginSection": 218, "offsetInEndSection": 347, "text": "HER2-targeting agents such as Herceptin\u00ae, Kadcyla\u00ae and ENHERTU\u00ae have been approved by the FDA for the treatment of breast cancer,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34532642", "endSection": "abstract" }, { "offsetInBeginSection": 799, "offsetInEndSection": 851, "text": " Herceptin toward ErbB2-positive breast cancer cells", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33468562", "endSection": "abstract" } ] }, { "body": "What are the main clinical components of the brain death exam?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33273410", "http://www.ncbi.nlm.nih.gov/pubmed/32312535", "http://www.ncbi.nlm.nih.gov/pubmed/32667440", "http://www.ncbi.nlm.nih.gov/pubmed/31456011", "http://www.ncbi.nlm.nih.gov/pubmed/21604079", "http://www.ncbi.nlm.nih.gov/pubmed/18514082", "http://www.ncbi.nlm.nih.gov/pubmed/32524528", "http://www.ncbi.nlm.nih.gov/pubmed/32648194", "http://www.ncbi.nlm.nih.gov/pubmed/22522447", "http://www.ncbi.nlm.nih.gov/pubmed/20724258" ], "ideal_answer": [ "The three essential findings in brain death are coma, absence of brain stem reflexes by neurologic exam including ancillary testing, and apnea. Studies can highlight the variability in practice in regard to the AT and supports the use of ancillary tests to determine BD in patients. Coma and brain stem reflexes can be determined by several ancillary tests Ancillary tests include electroencephalography, brainstem auditory evoked potentials, included somatosensory evoked potentials, transcranial Doppler ultrasonography, conventional cerebral angiography, and nuclear medicine flow study" ], "exact_answer": [ [ "coma" ], [ "neurologic exam", "neurologic criteria" ], [ "Apnea test" ], [ "Ancillary test" ], [ "somatosensory evoked potentials" ], [ "electroencephalography" ], [ "transcranial Doppler ultrasonography" ], [ "nuclear medicine flow study" ], [ "conventional cerebral angiography" ], [ "brainstem auditory evoked potentials" ] ], "type": "list", "id": "6235ee453a8413c6530000ac", "snippets": [ { "offsetInBeginSection": 979, "offsetInEndSection": 1348, "text": "A total of 157 ancillary tests were performed, including electroencephalogram (62%), computed tomography angiography (22%), transcranial Doppler ultrasound (6%), cerebral blood flow nuclear study (5%), cerebral angiography (4%), and other (1%). Forty-seven patients (53% of patients with AT) with confirmatory AT still underwent additional ancillary for BD confirmation", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32312535", "endSection": "abstract" }, { "offsetInBeginSection": 1349, "offsetInEndSection": 1469, "text": " Only 21 patients (12% of all patients) were declared brain-dead using confirmatory ATs alone without ancillary testing.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32312535", "endSection": "abstract" }, { "offsetInBeginSection": 1588, "offsetInEndSection": 1724, "text": "Our study highlights the variability in practice in regard to the AT and supports the use of ancillary tests to determine BD in patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32312535", "endSection": "abstract" }, { "offsetInBeginSection": 407, "offsetInEndSection": 1047, "text": "Details provided on the performance and interpretation of ancillary tests for determination of BD/DNC were variably provided and inconsistent. Approximately half of all protocols that included each ancillary test provided details about study performance: 63% of protocols that included conventional cerebral angiography, 55% of protocols that included electroencephalography, 50% of protocols that included somatosensory evoked potentials, 48% of protocols that included transcranial Doppler ultrasonography, 43% of protocols that included nuclear medicine flow study and 41% of protocols that included brainstem auditory evoked potentials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648194", "endSection": "abstract" }, { "offsetInBeginSection": 1566, "offsetInEndSection": 1660, "text": " Diagnostic requirements for ancillary testing in BD/DNC determination vary around the world. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32648194", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Apnea is one of the three cardinal findings in brain death (BD). Apnea testing (AT) is physiologically and practically complex.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32524528", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 51, "text": "Apnea Testing for the Determination of Brain Death:", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32524528", "endSection": "title" }, { "offsetInBeginSection": 1584, "offsetInEndSection": 1750, "text": " When conducting the neurologic examination and apnea test required for death by neurologic criteria determination in patients with suspected or confirmed coronavirus", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33273410", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 196, "text": "To discuss the challenges of conducting a death by neurologic criteria or brain death evaluation in the coronavirus disease 2019 era and provide guidance to mitigate viral transmission", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33273410", "endSection": "abstract" }, { "offsetInBeginSection": 1847, "offsetInEndSection": 1996, "text": "he final exam, negative brain flow was demonstrated 12 of 15 patients with craniectomy (80%) and 111 of 123 patients without craniectomy (90.2%). The", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31456011", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Use of CPAP as an alternative to the apnea test during the determination of brain death in hypoxemic patients", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32667440", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "The apnea test, which involves disconnection from the mechanical ventilator, presents risks during the determination of brain death, especially in hypoxemic patients. W", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32667440", "endSection": "abstract" }, { "offsetInBeginSection": 584, "offsetInEndSection": 770, "text": "The 2 main radionuclidic techniques used in evaluation of brain death are radionuclide angiography with nonlipophilic radiopharmaceuticals and parenchymal imaging with lipophilic agents.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18514082", "endSection": "abstract" }, { "offsetInBeginSection": 2143, "offsetInEndSection": 2552, "text": "are not a substitute for the neurologic examination. Ancillary studies may be used to assist the clinician in making the diagnosis of brain death (a) when components of the examination or apnea testing cannot be completed safely due to the underlying medical condition of the patient; (b) if there is uncertainty about the results of the neurologic examination; (c) if a medication effect may be present; or (", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22522447", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 538, "text": "BACKGROUND: Although the new Practice Parameters for brain death support a single examination, there is paucity of data comparing its impact to dual brain death (DBD) examinations.METHODS: We reviewed all brain deaths in our hospital over a 39-month period and compared the optional single brain death (SBD) exam requiring an apnea and a mandatory confirmatory blood flow test to the DBD for organ function at the time of death, rate of donation, and cost.RESULTS: Thirty-six patients had a SBD and 59 DBD exams, without any of them regai", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21604079", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "BACKGROUND: In Canada, ancillary tests, such as selective four vessels angiography (S4VA), are sometimes necessary for brain death (BD) diagnosis when the clinical exam cannot be completed or confounding factors ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20724258", "endSection": "abstract" }, { "offsetInBeginSection": 1237, "offsetInEndSection": 1571, "text": "We hypothesize that the existence of these apparent contradictions is related to differences in sensitivity of the physical examination and the confirmatory examinations, differences in localization of the physical examination and confirmatory tests, and differences between blood flow and cerebral function as markers of brain death.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18514082", "endSection": "abstract" }, { "offsetInBeginSection": 984, "offsetInEndSection": 1127, "text": "Nonetheless, on occasion patients clinically diagnosed with brain death will exhibit persistent intracranial blood flow or electrical activity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18514082", "endSection": "abstract" } ] }, { "body": "How does amphiregulin decrease the anti-proliferative effect of cetuximab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34893673" ], "ideal_answer": [ "In SNU-C4 and Caco-2 cells which were relatively sensitive to cetuximab among the seven CRC cell lines tested, AREG significantly decreased the anti-proliferative effect of cetuximab (p\u2009<\u20090.05) via AKT and ERK activation." ], "type": "summary", "id": "6237a94f3a8413c6530000b4", "snippets": [ { "offsetInBeginSection": 837, "offsetInEndSection": 1059, "text": "In SNU-C4 and Caco-2 cells which were relatively sensitive to cetuximab among the seven CRC cell lines tested, AREG significantly decreased the anti-proliferative effect of cetuximab (p\u2009<\u20090.05) via AKT and ERK activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34893673", "endSection": "abstract" } ] }, { "body": "Describe RCandy", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34864895" ], "ideal_answer": [ "RCandy is a platform-independent R package for rapid, simple, and flexible visualisation of recombination events in bacterial genomes." ], "type": "summary", "id": "621e5aa53a8413c65300004d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "RCandy: an R package for visualising homologous recombinations in bacterial genomes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864895", "endSection": "title" }, { "offsetInBeginSection": 419, "offsetInEndSection": 568, "text": "Here, we present RCandy, a platform-independent R package for rapid, simple, and flexible visualisation of recombination events in bacterial genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864895", "endSection": "abstract" } ] }, { "body": "What variables are included in the MuLBSTA score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32860431", "http://www.ncbi.nlm.nih.gov/pubmed/33729130", "http://www.ncbi.nlm.nih.gov/pubmed/32923449", "http://www.ncbi.nlm.nih.gov/pubmed/33573696" ], "ideal_answer": [ "MuLBSTA score includes Multilobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age." ], "exact_answer": [ [ "Multilobular infiltration" ], [ "hypo-Lymphocytosis" ], [ "Bacterial coinfection" ], [ "Smoking history" ], [ "hyper-Tension" ], [ "Age" ] ], "type": "list", "id": "61fbca4bc9dfcb9c09000011", "snippets": [ { "offsetInBeginSection": 456, "offsetInEndSection": 734, "text": "Patients were assessed according to HScore, SOFA (Sequential Organ Failure Assessment Score\u2009=\u2009SOFA), MuLBSTA Score (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension, and age), Brescia-COVID respiratory severity scale (BCRSS). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32860431", "endSection": "abstract" }, { "offsetInBeginSection": 2619, "offsetInEndSection": 2814, "text": "MuLBSTA score for viral pneumonia (multinodular infiltration, hypo-lymphocytosis, bacterial co infection, Total Leucocyte Count (TLC \u2264 0.8 x 109/L), smoking history, hyper-tension and age) score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33573696", "endSection": "abstract" }, { "offsetInBeginSection": 1406, "offsetInEndSection": 1994, "text": "There were significantly differences in ages (years old: 43\u00b113 vs. 57\u00b113), the proportion of patients with one chronic disease (17.7% vs. 55.6%), C-reactive protein [CRP (mg/L): 7.3 (2.3, 21.0) vs. 40.1 (18.8, 62.6)], lymphocyte count [LYM (\u00d7109/L): 1.3 (1.0, 1.8) vs. 0.8 (0.7, 1.1)], the neutrophil/lymphocyte ratio [NLR: 2.1 (1.6, 3.0) vs. 3.1 (2.2, 8.8)] and multilobularinltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension and age [MuLBSTA score: 5.0 (3.0, 5.0) vs. 5.0 (5.0, 7.0)] between mild/common group and severe/critical group (all P < 0.05). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33729130", "endSection": "abstract" }, { "offsetInBeginSection": 510, "offsetInEndSection": 812, "text": "g admission. The Multi-lobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age (MuLBSTA) Score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score were used to assess the death and intensive care unit (ICU) risks in all patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923449", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 673, "text": "The Multi-lobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age (MuLBSTA) Score and Confusion, Urea,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923449", "endSection": "abstract" }, { "offsetInBeginSection": 523, "offsetInEndSection": 812, "text": "The Multi-lobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age (MuLBSTA) Score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score were used to assess the death and intensive care unit (ICU) risks in all patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32923449", "endSection": "abstract" } ] }, { "body": "Which organisms are the focus of the Wormbase?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31552661", "http://www.ncbi.nlm.nih.gov/pubmed/31642470", "http://www.ncbi.nlm.nih.gov/pubmed/32185395", "http://www.ncbi.nlm.nih.gov/pubmed/29761466", "http://www.ncbi.nlm.nih.gov/pubmed/29069413" ], "ideal_answer": [ "WormBase continues to advance its practices on data acquisition, curation and retrieval to most effectively deliver comprehensive knowledge about Caenorhabditis elegans, and genomic information about other nematodes and parasitic flatworms." ], "exact_answer": [ [ "Caenorhabditis elegans" ], [ "nematodes" ], [ "parasitic flatworms" ] ], "type": "list", "id": "622cebe13a8413c65300009d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "The nematode C. elegans is a useful model organism for studying neuronal development and function due to its extremely simple, well-defined nervous system, translucence, short life cycle, and abundance of genetic tools (WormBase. http://wormbase.org , 2018; WormBook.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31552661", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31642470", "endSection": "abstract" }, { "offsetInBeginSection": 423, "offsetInEndSection": 593, "text": "WormBase (WB), the authoritative repository for research data on Caenorhabditis elegans and other nematodes, uses text mining (TM) to semi-automate its curation pipeline.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32185395", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 423, "text": "WormBase continues to advance its practices on data acquisition, curation and retrieval to most effectively deliver comprehensive knowledge about Caenorhabditis elegans, and genomic information about other nematodes and parasitic flatworms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29069413", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "WormBase ( www.wormbase.org ) provides the nematode research community with a centralized database for information pertaining to nematode genes and genomes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29761466", "endSection": "abstract" } ] }, { "body": "Is Ameloblastoma (AB) a benign tumor that never metastasizes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/21558899", "http://www.ncbi.nlm.nih.gov/pubmed/32712102", "http://www.ncbi.nlm.nih.gov/pubmed/23775022", "http://www.ncbi.nlm.nih.gov/pubmed/24374844", "http://www.ncbi.nlm.nih.gov/pubmed/6575436", "http://www.ncbi.nlm.nih.gov/pubmed/28944145", "http://www.ncbi.nlm.nih.gov/pubmed/31674718", "http://www.ncbi.nlm.nih.gov/pubmed/18230377" ], "ideal_answer": [ "Ameloblastomas are benign but locally invasive neoplasms which can be metastatic" ], "exact_answer": "no", "type": "yesno", "id": "622901d23a8413c65300008c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 215, "text": "Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31674718", "endSection": "abstract" }, { "offsetInBeginSection": 217, "offsetInEndSection": 313, "text": "AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31674718", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 313, "text": "Ameloblastomas are benign but locally invasive neoplasms which may grow to massive proportions and cause significant morbidity. Although some types of ameloblastoma can be treated predictably with aggressive surgical treatment, recurrent ameloblastoma and metastasising ameloblastoma are still difficult to treat.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32712102", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Ameloblastoma of the maxilla is a rare odontogenic tumor that rarely metastasizes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21558899", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "Ameloblastoma is an odontogenic tumor, usually benign, which rarely metastasizes to distant organs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18230377", "endSection": "abstract" }, { "offsetInBeginSection": 73, "offsetInEndSection": 218, "text": "Although ameloblastomas rarely metastasise, recurrences together with radical surgery often result in facial deformity and significant morbidity.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24374844", "endSection": "abstract" }, { "offsetInBeginSection": 74, "offsetInEndSection": 224, "text": "The World Health Organization (WHO) has defined malignant ameloblastoma (MA) as a histologically benign-appearing ameloblastoma that has metastasized.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28944145", "endSection": "abstract" }, { "offsetInBeginSection": 102, "offsetInEndSection": 250, "text": "Distant metastasis is a very rare condition and is designated as metastasizing (malignant) ameloblastoma despite its benign histological appearance.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23775022", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "Ameloblastoma is a locally invasive, histologically nonmalignant tumor that may on very rare occasions give rise to metastases.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6575436", "endSection": "abstract" } ] }, { "body": "What does PCAT6 stand for?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34620745" ], "ideal_answer": [ "PCAT6 stands for prostate cancer-associated transcript 6." ], "exact_answer": [ "rostate cancer-associated transcript 6" ], "type": "factoid", "id": "622668b13a8413c653000088", "snippets": [ { "offsetInBeginSection": 240, "offsetInEndSection": 391, "text": "In this work, we investigated the role and regulatory mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in breast cancer progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34620745", "endSection": "abstract" } ] }, { "body": "Is there any role of the 'Greek islands' in olfactory receptor choice?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30626972" ], "ideal_answer": [ "Yes. 'Greek islands' first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression." ], "exact_answer": "yes", "type": "yesno", "id": "620157bec9dfcb9c09000025", "snippets": [ { "offsetInBeginSection": 367, "offsetInEndSection": 1269, "text": "Chromatin conformation capture using in situ Hi-C on fluorescence-activated cell-sorted olfactory sensory neurons and their progenitors shows that olfactory receptor gene clusters from 18 chromosomes make specific and robust interchromosomal contacts that increase with differentiation of the cells. These contacts are orchestrated by intergenic olfactory receptor enhancers, the 'Greek islands', which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30626972", "endSection": "abstract" } ] }, { "body": "What is ASTRAL Score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32208843", "http://www.ncbi.nlm.nih.gov/pubmed/29994736", "http://www.ncbi.nlm.nih.gov/pubmed/22649218", "http://www.ncbi.nlm.nih.gov/pubmed/34431455", "http://www.ncbi.nlm.nih.gov/pubmed/30077603", "http://www.ncbi.nlm.nih.gov/pubmed/31706753", "http://www.ncbi.nlm.nih.gov/pubmed/23493731", "http://www.ncbi.nlm.nih.gov/pubmed/28236594", "http://www.ncbi.nlm.nih.gov/pubmed/23559264" ], "ideal_answer": [ "ASTRAL Score is used to predict prognosis of stroke patients." ], "type": "summary", "id": "62008456c9dfcb9c0900001e", "snippets": [ { "offsetInBeginSection": 724, "offsetInEndSection": 870, "text": "RESULTS: : Among all the scales, the ASTRAL score had the best accuracy for predicting 2-year prognosis in Chinese patients with ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431455", "endSection": "abstract" }, { "offsetInBeginSection": 1356, "offsetInEndSection": 1628, "text": "CONCLUSION: : The ASTRAL score had higher efficacy than the SPAN-100 and THRIVE scores in predicting 2-year adverse outcomes among Chinese patients with ischemic stroke, suggesting that it could be a valuable risk assessment tool for the 2-year prognosis of such patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431455", "endSection": "abstract" }, { "offsetInBeginSection": 1160, "offsetInEndSection": 1307, "text": "CONCLUSIONS: The ASTRAL score was an independent predictor of 3-month functional outcome and showed high predictive accuracy in patients with ESUS.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31706753", "endSection": "abstract" }, { "offsetInBeginSection": 501, "offsetInEndSection": 1060, "text": "We first validated point-based stroke prognostic scores (preadmission comorbidities, level of consciousness, age, and neurological deficit [PLAN] score, ischemic stroke predictive risk score [IScore], and acute stroke registry and analysis of Lausanne [ASTRAL] score in all patients; Houston intraarterial recanalization therapy [HIAT] score, totaled health risks in vascular events [THRIVE] score, and stroke prognostication using age and National Institutes of Health Stroke Scale-100 [SPAN-100] in patients who received reperfusion therapy) in our cohort. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32208843", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The Prognostic Value of the THRIVE Score, the iScore Score and the ASTRAL Score in Chinese Patients With Acute Ischemic Stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30077603", "endSection": "title" }, { "offsetInBeginSection": 83, "offsetInEndSection": 251, "text": "Many prediction tools have been developed to predict the risk of poor outcomes in patients after AIS, such as the THRIVE score, the iScore score, and the ASTRAL score. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30077603", "endSection": "abstract" }, { "offsetInBeginSection": 1786, "offsetInEndSection": 2012, "text": "CONCLUSIONS: The iScore score and the ASTRAL score reliably predict 1-year poor outcomes in Chinese patients with AIS, and the iScore score can accurately predict 1-year mortality and severe disability in Chinese AIS patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30077603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The Prognostic Value of the iScore, the PLAN Score, and the ASTRAL Score in Acute Ischemic Stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28236594", "endSection": "title" }, { "offsetInBeginSection": 244, "offsetInEndSection": 467, "text": "In this study, we evaluated the ability of 3 prognostic models including the iScore, the PLAN score, and the ASTRAL score in predicting clinical poor outcomes or mortality at 6 months in patients with acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28236594", "endSection": "abstract" }, { "offsetInBeginSection": 1148, "offsetInEndSection": 1351, "text": "CONCLUSIONS: The results of this study suggest that the iScore, the PLAN score, and the ASTRAL score were equal in predicting 6-month poor prognosis and mortality in patients with acute ischemic stroke. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28236594", "endSection": "abstract" }, { "offsetInBeginSection": 193, "offsetInEndSection": 450, "text": "THODS: Logistic regression was performed in the derivation cohort of previously independent patients with AIS (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) to identify predictors of unfavorable outcome (3-month modified Rankin Scale score >2). A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22649218", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "BACKGROUND AND PURPOSE: The ASTRAL score was recently introduced as a prognostic tool for acute ischemic stroke.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23493731", "endSection": "abstract" }, { "offsetInBeginSection": 1116, "offsetInEndSection": 1265, "text": "SIONS: ASTRAL score is a reliable tool to predict unfavorable outcome at 3 and 12 months after acute ischemic stroke in the Chinese population. It is", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23493731", "endSection": "abstract" }, { "offsetInBeginSection": 874, "offsetInEndSection": 1188, "text": "C-statistic of the ASTRAL score for the 2-year primary outcome was 0.79 (95% confidence interval [CI]: 0.78-0.80), and the Hosmer-Lemeshow goodness-of-fit test showed that the ASTRAL score fitted Chinese patients with ischemic stroke well (\u03c72\u00a0=\u00a09.83, P =\u00a00.277). The incidences of the primary outcome in the <5%, 5", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34431455", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "An integer-based score to predict functional outcome in acute ischemic stroke: the ASTRAL score.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22649218", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "ASTRAL score predicts 5-year dependence and mortality in acute ischemic stroke", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559264", "endSection": "title" }, { "offsetInBeginSection": 208, "offsetInEndSection": 389, "text": "n the last five years, several scores such as the ASTRAL, DRAGON, and THRIVE have been proposed as tools to help physicians predict the patient functional outcome after a stroke. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29994736", "endSection": "abstract" }, { "offsetInBeginSection": 366, "offsetInEndSection": 548, "text": " So, this study aimed to determine the ability of the THRIVE score, the iScore score, and the ASTRAL score in predicting clinical poor outcomes in Chinese patients with AIS at 1 year", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30077603", "endSection": "abstract" }, { "offsetInBeginSection": 82, "offsetInEndSection": 249, "text": " Many prediction tools have been developed to predict the risk of poor outcomes in patients after AIS, such as the THRIVE score, the iScore score, and the ASTRAL score", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30077603", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "ASTRAL score predicts 5-year dependence and mortality in acute ischemic stroke.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23559264", "endSection": "title" } ] }, { "body": "Is paxillin affected by RANKL?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32193744", "http://www.ncbi.nlm.nih.gov/pubmed/30609675", "http://www.ncbi.nlm.nih.gov/pubmed/22807029" ], "ideal_answer": [ "Yes,\nRANKL promotes paxillin serine and tyrosine phosphorylation." ], "exact_answer": "yes", "type": "yesno", "id": "622dc4b63a8413c6530000a4", "snippets": [ { "offsetInBeginSection": 899, "offsetInEndSection": 1329, "text": "Western blotting assays presented upregulated expressions of TNF receptor-activating factor 6 (TRAF6) and integrin \u03b23 induced by gingipains and RANKL compared to RANKL alone. Enhanced integrin-related signaling was also demonstrated by elevated phosphorylations of FAK and paxillin compared to control. Moreover, the pit resorption assays showed that gingipains augmented bone resorptive function of osteoclasts induced by RANKL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32193744", "endSection": "abstract" }, { "offsetInBeginSection": 1192, "offsetInEndSection": 1253, "text": "paxillin levels induced by RANKL in murine bone marrow cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30609675", "endSection": "abstract" }, { "offsetInBeginSection": 716, "offsetInEndSection": 776, "text": "RANKL promotes paxillin serine and tyrosine phosphorylation,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22807029", "endSection": "abstract" } ] }, { "body": "What organ is associated with a Gleason pattern or Gleason Score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/10652560", "http://www.ncbi.nlm.nih.gov/pubmed/12385930", "http://www.ncbi.nlm.nih.gov/pubmed/25189638", "http://www.ncbi.nlm.nih.gov/pubmed/32350585", "http://www.ncbi.nlm.nih.gov/pubmed/22367295", "http://www.ncbi.nlm.nih.gov/pubmed/25228336", "http://www.ncbi.nlm.nih.gov/pubmed/32686748", "http://www.ncbi.nlm.nih.gov/pubmed/15475927", "http://www.ncbi.nlm.nih.gov/pubmed/14562287", "http://www.ncbi.nlm.nih.gov/pubmed/21862072", "http://www.ncbi.nlm.nih.gov/pubmed/30363387", "http://www.ncbi.nlm.nih.gov/pubmed/17277764", "http://www.ncbi.nlm.nih.gov/pubmed/26439747" ], "ideal_answer": [ "The Gleason score is an important parameter for clinical outcome in prostate cancer patients", "The Gleason score is an important parameter for clinical outcome in prostate cancer patients." ], "exact_answer": [ "prostate" ], "type": "factoid", "id": "622b9d593a8413c653000095", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "The Gleason score is an important parameter for clinical outcome in prostate cancer patients", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32686748", "endSection": "abstract" }, { "offsetInBeginSection": 83, "offsetInEndSection": 124, "text": "Gleason score 8 prostate cancer patients.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32686748", "endSection": "title" }, { "offsetInBeginSection": 348, "offsetInEndSection": 390, "text": "Gleason score 8 prostate cancer patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32686748", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 114, "text": "Men with Gleason score 9-10 prostate cancer have worse outcomes compared to those with Gleason 8 disease.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32350585", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "OBJECTIVES: Most adenocarcinomas of the prostate with a Gleason score greater than 8 at radical prostatectomy have extraprostatic extension and a high risk of progression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12385930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26439747", "endSection": "title" }, { "offsetInBeginSection": 571, "offsetInEndSection": 730, "text": "eason score (GS) and predominant Gleason pattern were determined in prostate biopsies and in prostate tissue specimens, crosschecked by two uro-pathologists.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26439747", "endSection": "abstract" }, { "offsetInBeginSection": 1712, "offsetInEndSection": 1918, "text": "In conclusion, cribriform growth in Gleason grade 4 is a strong prognostic marker for distant metastasis and disease-specific death in patients with Gleason score 7 prostate cancer at radical prostatectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 192, "text": "Accurate recognition of Gleason pattern 5 (GP5) prostate adenocarcinoma (PCa) on core biopsy (NBX) is critical because it is associated with disease progression and the worst clinical outcome.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25228336", "endSection": "abstract" }, { "offsetInBeginSection": 1255, "offsetInEndSection": 1498, "text": " the first time that reelin is expressed in prostate cancer and not in benign prostate tissue and its expression occurs in higher Gleason score and correlates significantly with increasing of single Gleason patterns. This suggests reelin may b", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17277764", "endSection": "abstract" }, { "offsetInBeginSection": 89, "offsetInEndSection": 426, "text": "ne of the recent important modifications in the Gleason grading system recommended from the International Society of Urological Pathology consensus conference is recording the percentage of Gleason pattern 4 in the pathology reports of prostate needle biopsy and radical prostatectomy cases with Gleason score 7 prostatic adenocarcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30363387", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Usual and unusual histologic patterns of high Gleason score 8 to 10 adenocarcinoma of the prostate in needle biopsy tissue", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22367295", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The Gleason score of prostate adenocarcinomas is an important preoperative predictor of cancer behavior, and is used to help guide treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15475927", "endSection": "abstract" }, { "offsetInBeginSection": 935, "offsetInEndSection": 1093, "text": " frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns. While Gleason 3 patt", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17277764", "endSection": "abstract" }, { "offsetInBeginSection": 2843, "offsetInEndSection": 3036, "text": " of prostate cancer would occur within Gleason scores 3 to 10 even though higher scores are usually considered more aggressive forms of prostate cancers. Since our study is based upon a very li", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10652560", "endSection": "abstract" }, { "offsetInBeginSection": 713, "offsetInEndSection": 934, "text": "3 + 4 = 7 and Gleason score 4 + 3 = 7. Gleason score 4 + 3 = 7 showed an overall correlation with pathological stage (organ confined, focal extraprostatic extension, nonfocal extraprostatic extension, seminal vesicle inva", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21862072", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 490, "text": "We compared the Gleason scores found on needle biopsy with the grade and stage (organ-confined, extra-prostatic extension, positive seminal vesicles or lymph nodes) at radical prostatectomy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14562287", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "Prediction of outcome after radical prostatectomy in men with organ-confined Gleason score 8 to 10 adenocarcinoma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12385930", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "OBJECTIVES: Most adenocarcinomas of the prostate with a Gleason score greater than 8 at radical prostatectomy have extraprostatic extension and a high risk of ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12385930", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Usual and unusual histologic patterns of high Gleason score 8 to 10 adenocarcinoma of the prostate in needle biopsy tissue.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22367295", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25189638", "endSection": "title" }, { "offsetInBeginSection": 1697, "offsetInEndSection": 1893, "text": "A were similar in normal prostate and benign prostatic hyperplasia (BPH) whereas they varied consistently within and between Gleason histologic scores for prostate cancer. These variations showed ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10652560", "endSection": "abstract" } ] }, { "body": "How does FTO suppress pancreatic tumorigenesis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34484859" ], "ideal_answer": [ "Reduced expression of the m6A demethylase, fat mass and obesity-associated protein (FTO), was responsible for the high levels of m6A RNA modification in pancreatic cancer. Moreover, FTO demethylated the m6A modification of praja ring finger ubiquitin ligase 2 (PJA2), thereby reducing its mRNA decay, suppressing Wnt signaling, and ultimately restraining the proliferation, invasion, and metastasis of pancreatic cancer cells." ], "type": "summary", "id": "62262b353a8413c65300007f", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "m6A demethylase FTO suppresses pancreatic cancer tumorigenesis by demethylating PJA2 and inhibiting Wnt signaling.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34484859", "endSection": "title" }, { "offsetInBeginSection": 759, "offsetInEndSection": 1185, "text": "Reduced expression of the m6A demethylase, fat mass and obesity-associated protein (FTO), was responsible for the high levels of m6A RNA modification in pancreatic cancer. Moreover, FTO demethylated the m6A modification of praja ring finger ubiquitin ligase 2 (PJA2), thereby reducing its mRNA decay, suppressing Wnt signaling, and ultimately restraining the proliferation, invasion, and metastasis of pancreatic cancer cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34484859", "endSection": "abstract" } ] }, { "body": "Which tool has been developed to identify the glycan shielding of glycosylated proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34864901" ], "ideal_answer": [ "GLYCO (GLYcan COverage) is an in silico approach to quantify the glycan shielding of a protein surface. The software provides insights into glycan-dense/sparse regions of the entire protein surface or a subset of the protein surface. GLYCO calculates glycan shielding from a single coordinate file or from multiple coordinate files, for instance, as obtained from molecular dynamics simulations or by nuclear magnetic resonance spectroscopy structure determination, enabling analysis of glycan dynamics.", "GLYCO calculates glycan shielding from a single coordinate file or from multiple coordinate files, for instance, as obtained from molecular dynamics simulations or by nuclear magnetic resonance spectroscopy structure determination, enabling analysis of glycan dynamics." ], "exact_answer": [ "GLYCO" ], "type": "factoid", "id": "621e59ce3a8413c65300004c", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 68, "text": "GLYCO: a tool to quantify glycan shielding of glycosylated proteins.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864901", "endSection": "title" }, { "offsetInBeginSection": 389, "offsetInEndSection": 910, "text": "Here, we developed an in silico approach, GLYCO (GLYcan COverage), to quantify the glycan shielding of a protein surface. The software provides insights into glycan-dense/sparse regions of the entire protein surface or a subset of the protein surface. GLYCO calculates glycan shielding from a single coordinate file or from multiple coordinate files, for instance, as obtained from molecular dynamics simulations or by nuclear magnetic resonance spectroscopy structure determination, enabling analysis of glycan dynamics.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34864901", "endSection": "abstract" } ] }, { "body": "What are the targets of Tirbanibulin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33713299", "http://www.ncbi.nlm.nih.gov/pubmed/34349652", "http://www.ncbi.nlm.nih.gov/pubmed/33567191", "http://www.ncbi.nlm.nih.gov/pubmed/34783452", "http://www.ncbi.nlm.nih.gov/pubmed/33196758" ], "ideal_answer": [ "Tirbanibulin is Src kinase signaling inhibitor and tubulin polymerisation inhibitor that is being developed for the topical treatment of actinic keratosis, and psoriasis." ], "exact_answer": [ [ "Src kinase signaling" ], [ "tubulin polymerisation" ] ], "type": "list", "id": "61f7ceeb882a024a1000002e", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "BACKGROUND: The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33567191", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 238, "text": "Tirbanibulin (Klisyri\u00ae) is a first-in-class Src kinase signaling inhibitor and tubulin polymerisation inhibitor being developed by Athenex in conjunction with global partners for the topical treatment of actinic keratosis, and psoriasis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33713299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Tirbanibulin is a novel tubulin polymerization and Src kinase signaling inhibitor.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34783452", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34349652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Tirbanibulin (Klisyri\u00ae) is a first-in-class Src kinase signaling inhibitor and tubulin polymerisation inhibitor being developed by Athenex in conjunction with global partners for the topical treatment of actinic keratosis, and psoriasis. Based on the data fro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33713299", "endSection": "abstract" }, { "offsetInBeginSection": 170, "offsetInEndSection": 391, "text": "Tirbanibulin, a novel potent anti-proliferative synthetic agent that inhibits tubulin polymerization and Src kinase signalling, is being developed as a convenient, safe, and effective field treatment of actinic keratosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33196758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 187, "text": "Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34349652", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Tirbanibulin is a novel tubulin polymerization and Src kinase signaling inhibitor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34783452", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 386, "text": "atment. Tirbanibulin, a novel potent anti-proliferative synthetic agent that inhibits tubulin polymerization and Src kinase signalling, is being developed as a convenient, safe, and effective field treatment of actinic kerat", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33196758", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 237, "text": "Tirbanibulin (Klisyri\u00ae) is a first-in-class Src kinase signaling inhibitor and tubulin polymerisation inhibitor being developed by Athenex in conjunction with global partners for the topical treatment of actinic keratosis, and psoriasis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33713299", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 389, "text": "BACKGROUND: The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.METHODS: In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33567191", "endSection": "abstract" } ] }, { "body": "Is retinol binding protein 4 an adipokine?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33199363", "http://www.ncbi.nlm.nih.gov/pubmed/33484131", "http://www.ncbi.nlm.nih.gov/pubmed/34575030" ], "ideal_answer": [ "Yes,\nRetinol-binding protein 4 (RBP4) is a prominent adipokine." ], "exact_answer": "yes", "type": "yesno", "id": "622b95dc3a8413c653000092", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Systematic Quantification of Neurotrophic Adipokines RBP4, PEDF, and Clusterin in Human Cerebrospinal Fluid and Serum.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33484131", "endSection": "title" }, { "offsetInBeginSection": 91, "offsetInEndSection": 150, "text": "Retinol-binding protein 4 (RBP4) is a prominent adipokine i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33199363", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 105, "text": "Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34575030", "endSection": "abstract" } ] }, { "body": "What is the function of BACH1", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23181164", "http://www.ncbi.nlm.nih.gov/pubmed/31939443", "http://www.ncbi.nlm.nih.gov/pubmed/11301010", "http://www.ncbi.nlm.nih.gov/pubmed/12511571", "http://www.ncbi.nlm.nih.gov/pubmed/34322202", "http://www.ncbi.nlm.nih.gov/pubmed/15809329", "http://www.ncbi.nlm.nih.gov/pubmed/34339740", "http://www.ncbi.nlm.nih.gov/pubmed/27959382", "http://www.ncbi.nlm.nih.gov/pubmed/19439223", "http://www.ncbi.nlm.nih.gov/pubmed/30370001", "http://www.ncbi.nlm.nih.gov/pubmed/21873975", "http://www.ncbi.nlm.nih.gov/pubmed/17701549", "http://www.ncbi.nlm.nih.gov/pubmed/18555605", "http://www.ncbi.nlm.nih.gov/pubmed/8887638", "http://www.ncbi.nlm.nih.gov/pubmed/34605540", "http://www.ncbi.nlm.nih.gov/pubmed/18325350", "http://www.ncbi.nlm.nih.gov/pubmed/26377036", "http://www.ncbi.nlm.nih.gov/pubmed/20501657", "http://www.ncbi.nlm.nih.gov/pubmed/34482423", "http://www.ncbi.nlm.nih.gov/pubmed/33503260", "http://www.ncbi.nlm.nih.gov/pubmed/18550526", "http://www.ncbi.nlm.nih.gov/pubmed/15743416", "http://www.ncbi.nlm.nih.gov/pubmed/33373621", "http://www.ncbi.nlm.nih.gov/pubmed/19119918", "http://www.ncbi.nlm.nih.gov/pubmed/15855052", "http://www.ncbi.nlm.nih.gov/pubmed/16462773", "http://www.ncbi.nlm.nih.gov/pubmed/22107958", "http://www.ncbi.nlm.nih.gov/pubmed/22348305", "http://www.ncbi.nlm.nih.gov/pubmed/21812759", "http://www.ncbi.nlm.nih.gov/pubmed/21473739" ], "ideal_answer": [ "BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar" ], "type": "summary", "id": "622cbb4e3a8413c65300009a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "Regulatory mechanisms of heme regulatory protein BACH1", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34482423", "endSection": "title" }, { "offsetInBeginSection": 143, "offsetInEndSection": 306, "text": "(BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34482423", "endSection": "abstract" }, { "offsetInBeginSection": 530, "offsetInEndSection": 613, "text": "BACH1 is a ubiquitous master regulator of the cellular response to oxidative stress", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34605540", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Bach1 is a known transcriptional repressor of the heme oxygenase-1 (HO-1) gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33373621", "endSection": "abstract" }, { "offsetInBeginSection": 300, "offsetInEndSection": 345, "text": "Here, we report a transcription factor BACH1,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33503260", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8887638", "endSection": "title" }, { "offsetInBeginSection": 364, "offsetInEndSection": 436, "text": "we have identified two novel bZip transcription factors, Bach1 and Bach2", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8887638", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Bach1, a heme-dependent transcription factor, reveals presence of multiple heme binding sites with distinct coordination structure.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17701549", "endSection": "title" }, { "offsetInBeginSection": 324, "offsetInEndSection": 507, "text": "Proteomics analysis of Bach1 complex revealed its interaction with p19(ARF), a tumor suppressor that competitively inhibited the Bach1-p53 interaction when overexpressed within cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22348305", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Bach1 is a transcriptional repressor which modulates several critical transcriptional responses, such as the expression of the heme oxygenase-1 (HO-1) gene in response to oxidative stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23181164", "endSection": "abstract" }, { "offsetInBeginSection": 86, "offsetInEndSection": 141, "text": "Bach1 is a mammalian transcriptional repressor of HO-1.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18325350", "endSection": "abstract" }, { "offsetInBeginSection": 71, "offsetInEndSection": 238, "text": "Bach1 is an important transcriptional repressor that acts by modulating oxidative stress and represents a potential target in the treatment of pulmonary fibrosis\u00a0(PF).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27959382", "endSection": "abstract" }, { "offsetInBeginSection": 801, "offsetInEndSection": 1019, "text": "Overexpression of Bach1, together with MafK, represses basal and UVA-mediated HO-1 protein expression, whereas silencing of the Bach1 gene by Bach1-specific siRNAs causes robust enhancement of constitutive HO-1 levels.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22107958", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "BTB and CNC homologue 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21473739", "endSection": "abstract" }, { "offsetInBeginSection": 447, "offsetInEndSection": 680, "text": "tly, BTB and CNC homology 1 (BACH1), a heme-regulated transcription factor that represses genes involved in iron and heme metabolism in normal cells, was shown to shape the metabolism and metastatic potential of cancer cells. The gro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34339740", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 724, "text": "reveal BACH1 as a novel let-7-regulated transcription factor that induces matrix metalloproteinase1 (MMP1) expression and promotes metastasis. An RKIP path", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21873975", "endSection": "abstract" }, { "offsetInBeginSection": 372, "offsetInEndSection": 529, "text": "tory. The BTB and CNC homology 1 (BACH1) protein is known to regulate \u03b1- and \u03b2-globin gene transcriptions during the terminal differentiation of erythroid ce", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26377036", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer-promoter activity and maintains pluripotency", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33503260", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "Bach1 functions as a transcriptional repressor of heme oxygenase-1 (HO-1) and the beta-globin genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15809329", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Bach1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12511571", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Bach1 is a transcriptional repressor of the cytoprotective enzyme heme oxygenase-1 (HO-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15743416", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 538, "text": "Bach1 is a transcriptional repressor of the HO-1 gene, and plays a critical role in tissue protection from oxidative stress by reperfusion injury of the myocardium.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18555605", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 291, "text": "Bach1 is a transcriptional repressor of the HO-1 gene (Hmox-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19119918", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 69, "text": "Bach1 as a regulator of mitosis, beyond its transcriptional function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23181164", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Bach1 is a transcriptional repressor of the heme oxygenase (HO)-1 gene.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19439223", "endSection": "abstract" }, { "offsetInBeginSection": 1183, "offsetInEndSection": 1303, "text": "Thus, Bach1 plays an important role in regulating the constitutive and inducible expression levels of HO-1 in the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18555605", "endSection": "abstract" }, { "offsetInBeginSection": 343, "offsetInEndSection": 492, "text": "BACH1 plays important roles both in phosphorylated as well as dephosphorylated state and functions in coordination with multiple signaling molecules.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34322202", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 322, "text": "he Maf recognition element (MARE). Because Bach1 is a repressor of the oxidative stress response, we examined the function(s) of Bach1 in keratinocyte", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20501657", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 277, "text": "The transcription factor BTB and CNC homology 1 (Bach1) is widely expressed in most mammalian tissues and functions primarily as a transcriptional suppressor by heterodimerizing with small Maf proteins and binding to Maf recognition elements in the promoters of targeted genes.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30370001", "endSection": "abstract" }, { "offsetInBeginSection": 1205, "offsetInEndSection": 1357, "text": "Therefore, Bach1 functions as a hypoxia-inducible repressor for the HO-1 gene, thereby contributing to fine-tuning of oxygen homeostasis in human cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12511571", "endSection": "abstract" }, { "offsetInBeginSection": 339, "offsetInEndSection": 436, "text": "Thus, BACH1 is a likely candidate for mediating BRCA1 DNA repair and tumor suppression functions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16462773", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11301010", "endSection": "title" }, { "offsetInBeginSection": 715, "offsetInEndSection": 990, "text": "Transcription factor BACH1 [BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1] binds to ARE-like sequences, functioning as a transcriptional repressor in a subset of ARE-regulated genes, thus antagonizing the activator function of Nrf2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21812759", "endSection": "abstract" }, { "offsetInBeginSection": 1145, "offsetInEndSection": 1336, "text": "The loss of BACH1 function in human keratinocytes results almost exclusively in HMOX1 induction, suggesting that BACH1 may function as a rheostat regulating levels of intracellular free heme.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18550526", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 63, "text": "BACH1 is a DNA repair protein supporting BRCA1 damage response.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16462773", "endSection": "title" }, { "offsetInBeginSection": 116, "offsetInEndSection": 205, "text": "The N-terminus of BACH1 functions in DNA metabolism as DNA-dependent ATPase and helicase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34322202", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Bach1 is a transcriptional repressor of heme oxygenase-1, one of the most inducible phase 2 proteins.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15855052", "endSection": "abstract" }, { "offsetInBeginSection": 750, "offsetInEndSection": 870, "text": "Our findings suggest that Bach1 might mediate the regulation of mitotic chromosomes under conditions of cellular stress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23181164", "endSection": "abstract" }, { "offsetInBeginSection": 189, "offsetInEndSection": 302, "text": "In our recent study, we found that Bach1 possesses a novel role in mitotic chromosome alignment during metaphase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23181164", "endSection": "abstract" }, { "offsetInBeginSection": 6, "offsetInEndSection": 290, "text": "The purpose of this study was to investigate the potential correlation between metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the transcription factor BTB and CNC homology 1 (BACH1) and their clinicopathological significance in triple-negative breast cancer (TNBC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31939443", "endSection": "abstract" } ] }, { "body": "What does the gene symbol EREG stand for?", "_type": "factoid", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34667080" ], "_body": "epiregulin", "ideal_answer": [ "The gene symbol EREG stands for the gene epiregulin." ], "exact_answer": [ "epiregulin" ], "type": "factoid", "id": "6237a5513a8413c6530000b0", "snippets": [ { "offsetInBeginSection": 268, "offsetInEndSection": 569, "text": "We found that epidermal growth factor (EGF)-deficient cells exhibited lower basal ERK activity than the cells deficient in heparin-binding EGF (HBEGF), transforming growth factor alpha (TGF\u03b1) or epiregulin (EREG), but all cell lines deficient in a single EGFR ligand retained the ERK activation waves.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34667080", "endSection": "abstract" } ] }, { "body": "Which tool has been developed for proteome-wide detection of membrane lipid-binding proteins?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27048983" ], "ideal_answer": [ "MBPpred is a profile Hidden Markov Model based method capable of detecting Membrane Binding Proteins (MBPs) from information encoded in their amino acid sequence." ], "exact_answer": [ "MBPpred" ], "type": "factoid", "id": "62005e02c9dfcb9c09000018", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "MBPpred: Proteome-wide detection of membrane lipid-binding proteins using profile Hidden Markov Models.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048983", "endSection": "title" }, { "offsetInBeginSection": 355, "offsetInEndSection": 1018, "text": "Here we report a profile Hidden Markov Model based method capable of detecting Membrane Binding Proteins (MBPs) from information encoded in their amino acid sequence, called MBPpred. The method identifies MBPs that contain one or more of the Membrane Binding Domains (MBDs) that have been described to date, and further classifies these proteins based on their position in respect to the membrane, either as peripheral or transmembrane. MBPpred is available online at http://bioinformatics.biol.uoa.gr/MBPpred. This method was applied in selected eukaryotic proteomes, in order to examine the characteristics they exhibit in various eukaryotic kingdoms and phyla.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27048983", "endSection": "abstract" } ] }, { "body": "What disease can be treated with Avacopan?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33625803", "http://www.ncbi.nlm.nih.gov/pubmed/28400446", "http://www.ncbi.nlm.nih.gov/pubmed/34484454", "http://www.ncbi.nlm.nih.gov/pubmed/34473462", "http://www.ncbi.nlm.nih.gov/pubmed/34826105", "http://www.ncbi.nlm.nih.gov/pubmed/34006155", "http://www.ncbi.nlm.nih.gov/pubmed/33164993", "http://www.ncbi.nlm.nih.gov/pubmed/33596356", "http://www.ncbi.nlm.nih.gov/pubmed/29718732", "http://www.ncbi.nlm.nih.gov/pubmed/34224265", "http://www.ncbi.nlm.nih.gov/pubmed/34553355", "http://www.ncbi.nlm.nih.gov/pubmed/33128347", "http://www.ncbi.nlm.nih.gov/pubmed/32088663" ], "ideal_answer": [ "Avacopan is effective for ANCA-associated vasculitis." ], "exact_answer": [ "ANCA-associated vasculitis" ], "type": "factoid", "id": "61f7c883882a024a10000026", "snippets": [ { "offsetInBeginSection": 1009, "offsetInEndSection": 1397, "text": "Current therapies are often effective in inducing and maintaining remission but are associated with a range of toxicities. Several new therapies are in development for ANCA vasculitis. Avacopan, an orally administered inhibitor of the complement fragment 5a (C5a) receptor, has been assessed in a phase 3 clinical trial and may play a role in reducing the cumulative glucocorticoid dose. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34473462", "endSection": "abstract" }, { "offsetInBeginSection": 846, "offsetInEndSection": 973, "text": "New treatment approaches, such as the C5a receptor inhibitor avacopan could enable a\u00a0minimized steroid treatment in the future.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34484454", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 241, "text": "GPA/MPA INDUCTION OF REMISSION: \u2002As demonstrated in the ADVOCATE-trial avacopan allows for a substantial reduction of glucocorticoid (GC) use during induction of remission. A future role of avacopan in the treatment of GPA and MPA is likely.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34553355", "endSection": "abstract" }, { "offsetInBeginSection": 1058, "offsetInEndSection": 1216, "text": "Avacopan has shown significant promise in ANCA-associated vasculitis as part of a glucocorticoid-free induction regimen in a recently completed phase 3 trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33164993", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "In ANCA-associated vasculitis, avacopan was superior to prednisone taper for sustained remission", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34224265", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "SOURCE CITATION: Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384:599-609. 33596356.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34224265", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Avacopan for the Treatment of ANCA-Associated Vasculitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33596356", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: The C5a receptor inhibitor avacopan is being studied for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33596356", "endSection": "abstract" }, { "offsetInBeginSection": 1886, "offsetInEndSection": 2149, "text": "CONCLUSIONS: In this trial involving patients with ANCA-associated vasculitis, avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33596356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 82, "text": "Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28400446", "endSection": "title" }, { "offsetInBeginSection": 431, "offsetInEndSection": 592, "text": "tly, new molecules are being developed and some of them have already demonstrated clinical efficacy, such as avacopan (C5aR blocker) in ANCA vasculitis. As for k", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33625803", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 769, "text": "ber 2021, avacopan received its first approval in Japan for the treatment of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), the two most common forms of ANCA-associated vasculitis, where it is being commercialized by Kissei Pharmaceutical through a partnership with Vifor Pharma. In October 20", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34826105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Avacopan for the treatment of ANCA-associated vasculitis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34006155", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Avacopan for the Treatment of ANCA-Associated Vasculitis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33596356", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Avacopan in the treatment of ANCA-associated vasculitis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29718732", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "In ANCA-associated vasculitis, avacopan was superior to prednisone taper for sustained remission.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34224265", "endSection": "title" }, { "offsetInBeginSection": 772, "offsetInEndSection": 1045, "text": " avacopan was approved in the USA as an adjunctive treatment in adults for severe active ANCA-associated vasculitis (specifically MPA and GPA) in combination with standard therapy including glucocorticoids (avacopan does not eliminate glucocorticoid use). Avacopan has rece", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34826105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 218, "text": "Avacopan (TAVNEOS\u2122) is a complement 5a receptor (C5aR) antagonist developed by ChemoCentryx for the treatment of autoimmune diseases including anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34826105", "endSection": "abstract" }, { "offsetInBeginSection": 809, "offsetInEndSection": 938, "text": "al will evaluate if avacopan replaces the need for chronic glucocorticoids in the treatment of ANCA-associated vasculitis.OBJECTI", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32088663", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 57, "text": "Avacopan for the treatment of ANCA-associated vasculitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34006155", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "Avacopan in the treatment of ANCA-associated vasculitis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29718732", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 290, "text": "OBJECTIVE: This study aimed to evaluate the safety of avacopan, an orally administered C5a receptor inhibitor, for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in addition to standard-of-care (SOC) treatment with glucocorticoids with cyclophosphamide or", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33128347", "endSection": "abstract" }, { "offsetInBeginSection": 1876, "offsetInEndSection": 2024, "text": "rednisone.CONCLUSIONS: In this trial involving patients with ANCA-associated vasculitis, avacopan was noninferior but not superior to prednisone tap", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33596356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 213, "text": "Avacopan (TAVNEOS\u2122) is a complement 5a receptor (C5aR) antagonist developed by ChemoCentryx for the treatment of autoimmune diseases including anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34826105", "endSection": "abstract" }, { "offsetInBeginSection": 439, "offsetInEndSection": 755, "text": "In September 2021, avacopan received its first approval in Japan for the treatment of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), the two most common forms of ANCA-associated vasculitis, where it is being commercialized by Kissei Pharmaceutical through a partnership with Vifor Pharma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34826105", "endSection": "abstract" }, { "offsetInBeginSection": 756, "offsetInEndSection": 1027, "text": "In October 2021, avacopan was approved in the USA as an adjunctive treatment in adults for severe active ANCA-associated vasculitis (specifically MPA and GPA) in combination with standard therapy including glucocorticoids (avacopan does not eliminate glucocorticoid use).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34826105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 343, "text": "BACKGROUND: The C5a receptor inhibitor avacopan is being studied for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.METHODS: In this randomized, controlled trial, we assigned patients with ANCA-associated vasculitis in a 1:1 ratio to receive oral avacopan at a dose of 30 mg twice daily or oral prednisone on", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33596356", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 470, "text": "OBJECTIVE: This study aimed to evaluate the safety of avacopan, an orally administered C5a receptor inhibitor, for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in addition to standard-of-care (SOC) treatment with glucocorticoids with cyclophosphamide or rituximab.METHODS: In this randomized 12-week study, twice daily avacopan (10 mg or 30 mg) plus SOC was assessed versus SOC only in patients with newly diagnosed/relapsing ANCA-as", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33128347", "endSection": "abstract" }, { "offsetInBeginSection": 789, "offsetInEndSection": 1505, "text": "onephritis. This trial will evaluate if avacopan replaces the need for chronic glucocorticoids in the treatment of ANCA-associated vasculitis.OBJECTIVE: The aim of this study is to determine the proportions of patients in remission at week 26 and with sustained remission at week 52, defined as Birmingham Vasculitis Activity Score=0, and not taking glucocorticoids within the 4 weeks before week 26 and week 52, respectively.METHODS: The Avacopan Development in Vasculitis to Obtain Corticosteroid elimination and Therapeutic Efficacy study is a randomized, double-blind, active-comparator (prednisone), 2-arm study evaluating the safety and efficacy of avacopan versus prednisone, administered in combination with ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32088663", "endSection": "abstract" } ] }, { "body": "Is HYDIN (Hydrocephalus-inducing protein homolog) an axonemal protein?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/17683645", "http://www.ncbi.nlm.nih.gov/pubmed/17296793" ], "ideal_answer": [ "Yes,\nHYDIN is a axonemal protein." ], "exact_answer": "yes", "type": "yesno", "id": "622ce21d3a8413c65300009c", "snippets": [ { "offsetInBeginSection": 198, "offsetInEndSection": 292, "text": "Hydin was recently identified as an axonemal protein; however, its function is as yet unknown.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17683645", "endSection": "abstract" }, { "offsetInBeginSection": 747, "offsetInEndSection": 891, "text": "precise axonemal location of hydin, a protein that, when mutated, causes hydrocephalus, and defined a unique role for hydin in ciliary motility.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17296793", "endSection": "abstract" } ] }, { "body": "What disease is also known as Bechterew's Disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/6461592", "http://www.ncbi.nlm.nih.gov/pubmed/6983935", "http://www.ncbi.nlm.nih.gov/pubmed/25050151", "http://www.ncbi.nlm.nih.gov/pubmed/11803718", "http://www.ncbi.nlm.nih.gov/pubmed/22744304", "http://www.ncbi.nlm.nih.gov/pubmed/18650743", "http://www.ncbi.nlm.nih.gov/pubmed/32349490", "http://www.ncbi.nlm.nih.gov/pubmed/3923615", "http://www.ncbi.nlm.nih.gov/pubmed/29101454", "http://www.ncbi.nlm.nih.gov/pubmed/2233790", "http://www.ncbi.nlm.nih.gov/pubmed/22085520" ], "ideal_answer": [ "Ankylosing spondylitis (Bechterew's disease) is the most typical form of axial SpA whereby sacroiliitis can be found on X-rays of the SI joints." ], "exact_answer": [ "Ankylosing spondylitis" ], "type": "factoid", "id": "622b9e743a8413c653000097", "snippets": [ { "offsetInBeginSection": 229, "offsetInEndSection": 373, "text": "Ankylosing spondylitis (Bechterew's disease) is the most typical form of axial SpA whereby sacroiliitis can be found on X-rays of the SI joints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22085520", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "[Special considerations in therapy of injuries of the cervical spine in ankylosing spondylitis (Bechterew disease)]", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11803718", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Ankylosing spondylitis (AS) or Bechterew disease is a chronic, usually progressive, systemic inflammatory joint disease, which predominantly affects the spine and sacroiliac joints. In ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050151", "endSection": "abstract" }, { "offsetInBeginSection": 2, "offsetInEndSection": 106, "text": "iagnosis and therapy of axial spondyloarthritis including ankylosing spondylitis (Bechterew's disease)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22744304", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Hyperplasia of the coronoid process in patients with ankylosing spondylitis (Bechterew disease)", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18650743", "endSection": "title" }, { "offsetInBeginSection": 2, "offsetInEndSection": 115, "text": "pecial considerations in therapy of injuries of the cervical spine in ankylosing spondylitis (Bechterew disease)]", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11803718", "endSection": "title" }, { "offsetInBeginSection": 2, "offsetInEndSection": 113, "text": "irected cloning of the HLA-B27 gene isolated from a patient with ankylosing spondylitis (Bechterew's disease)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2233790", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "Bechterew's syndrome (ankylosing spondylitis).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/3923615", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "Ankylosing spondylitis (AS) or Bechterew disease is a chronic, usually progressive, systemic inflammatory joint disease, which predominantly affects the spine and sacroiliac joints.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25050151", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "[Ankylosing spondylitis (Bechterew's disease)--a current review (author's transl)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6461592", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "The distribution of clinical findings in Bechterew's syndrome (ankylosing spondylitis) suggests distinct genetic subgroups.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/6983935", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Hyperplasia of the coronoid process in patients with ankylosing spondylitis (Bechterew disease).", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18650743", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "[Surgical management of ankylosing spondylitis (Bechterew's disease)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29101454", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "[Diagnosis and therapy of axial spondyloarthritis including ankylosing spondylitis (Bechterew's disease)].", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22744304", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 205, "text": "Ankylosing spondylitis (AS) or else Bechterews\u00a0or Marie-Str\u00fcmpells\u00a0disease is a\u00a0chronic inflammatory autoimmune disease affecting preferentially the spine in the form of sacroileitis and spondylitis [1,2].", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32349490", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Although involvement of the temporomandibular joint in patients with ankylosing spondylitis (AS, Bechterew disease) has been described previously", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18650743", "endSection": "abstract" } ] }, { "body": "Through which pathway does epiregulin promote leptin secretion?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30400011" ], "ideal_answer": [ "EREG increased leptin production and secretion in a dose-dependent manner in iAb fat explants via the EGFR/MAPK pathway." ], "exact_answer": [ "EGFR/MAPK pathway" ], "type": "factoid", "id": "6237ac143a8413c6530000b7", "snippets": [ { "offsetInBeginSection": 724, "offsetInEndSection": 845, "text": "EREG increased leptin production and secretion in a dose-dependent manner in iAb fat explants via the EGFR/MAPK pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30400011", "endSection": "abstract" } ] }, { "body": "Are there any R packages that help with visualizing data on spirals?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34849585" ], "ideal_answer": [ "Yes. Spiralize is an R package for visualizing data on spirals." ], "exact_answer": "yes", "type": "yesno", "id": "621e62c33a8413c653000050", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 56, "text": "spiralize: an R package for Visualizing Data on Spirals.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34849585", "endSection": "title" }, { "offsetInBeginSection": 9, "offsetInEndSection": 584, "text": "Spiral layout has two major advantages for data visualization. First, it is able to visualize data with long axes, which greatly improves the resolution of visualization. Second, it is efficient for time series data to reveal periodic patterns. Here we present the R package spiralize that provides a general solution for visualizing data on spirals. spiralize implements numerous graphics functions so that self-defined high-level graphics can be easily implemented by users. The flexibility and power of spiralize are demonstrated by five examples from real-world datasets.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34849585", "endSection": "abstract" } ] }, { "body": "Was ALVAC-HIV effective for HIV prevention in the HVTN 702 trial?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33761206", "http://www.ncbi.nlm.nih.gov/pubmed/34029515", "http://www.ncbi.nlm.nih.gov/pubmed/32554928" ], "ideal_answer": [ "No. The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity" ], "exact_answer": "no", "type": "yesno", "id": "61faa3bac9dfcb9c0900000b", "snippets": [ { "offsetInBeginSection": 1258, "offsetInEndSection": 1662, "text": "During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P\u2009=\u20090.84).CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33761206", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 433, "text": "The advanced-phase HIV prevention vaccine trials done in South Africa (HVTN 702) and in Thailand (RV144), which both investigated canarypox vectors and adjuvanted gp120 proteins, gave rise to different results. The South African trial did not find vaccine efficacy, whereas the Thai trial had modest, but statistically significant, success with the modified intention-to-treat analysis prespecified in the protocols of both studies. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34029515", "endSection": "abstract" }, { "offsetInBeginSection": 280, "offsetInEndSection": 450, "text": "However, with the recent failure of the HVTN 702 clinical trial, comprehensive profiling of humoral immune responses may provide insight for these disappointing results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32554928", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 238, "text": "A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33761206", "endSection": "abstract" }, { "offsetInBeginSection": 1228, "offsetInEndSection": 1567, "text": "e vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P\u2009=\u20090.84).CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa d", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33761206", "endSection": "abstract" } ] }, { "body": "Do Afamin bind Vitamin E?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30247793", "http://www.ncbi.nlm.nih.gov/pubmed/33409873", "http://www.ncbi.nlm.nih.gov/pubmed/30220025", "http://www.ncbi.nlm.nih.gov/pubmed/29587878", "http://www.ncbi.nlm.nih.gov/pubmed/28877915" ], "ideal_answer": [ "Yes,\nAfamin is a plasma vitamin E-binding glycoprotein." ], "exact_answer": "yes", "type": "yesno", "id": "622baf3f3a8413c653000099", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The plasma glycoprotein afamin has been previously identified as an alternative carrier protein for vitamin E in extravascular fluids such as plasma and cerebrospinal, ovarian follicular, and seminal fluids.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33409873", "endSection": "abstract" }, { "offsetInBeginSection": 128, "offsetInEndSection": 179, "text": "afamin, a vitamin E-binding protein in human plasma", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29587878", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 172, "text": "the human vitamin E-binding protein afamin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30220025", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 61, "text": "Afamin is a plasma vitamin E-binding glycoprotein", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30247793", "endSection": "abstract" }, { "offsetInBeginSection": 11, "offsetInEndSection": 165, "text": "The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28877915", "endSection": "abstract" } ] }, { "body": "Is disruption of immune regulation mechanisms associated with adverse pregnancy outcomes, including preeclampsia (PE)?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34576285", "http://www.ncbi.nlm.nih.gov/pubmed/9272206", "http://www.ncbi.nlm.nih.gov/pubmed/34847253", "http://www.ncbi.nlm.nih.gov/pubmed/32161574", "http://www.ncbi.nlm.nih.gov/pubmed/19683334", "http://www.ncbi.nlm.nih.gov/pubmed/34412079", "http://www.ncbi.nlm.nih.gov/pubmed/21498785", "http://www.ncbi.nlm.nih.gov/pubmed/34509865", "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "http://www.ncbi.nlm.nih.gov/pubmed/32573856", "http://www.ncbi.nlm.nih.gov/pubmed/27108670", "http://www.ncbi.nlm.nih.gov/pubmed/24520479", "http://www.ncbi.nlm.nih.gov/pubmed/34191338", "http://www.ncbi.nlm.nih.gov/pubmed/30058156", "http://www.ncbi.nlm.nih.gov/pubmed/31608721", "http://www.ncbi.nlm.nih.gov/pubmed/29756666", "http://www.ncbi.nlm.nih.gov/pubmed/34599631" ], "ideal_answer": [ "Inflammation and oxidative stress at the maternal-fetal interface characterize the placental dysfunction that underlies the pregnancy disorder preeclampsia.", "Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE)" ], "exact_answer": "yes", "type": "yesno", "id": "622632483a8413c653000081", "snippets": [ { "offsetInBeginSection": 11, "offsetInEndSection": 244, "text": " Maternal systemic and placental inflammatory responses participate in the pathogenesis of hypertensive disorders of pregnancy including preeclampsia, a pregnancy-specific syndrome, although the role of inflammation remains unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34412079", "endSection": "abstract" }, { "offsetInBeginSection": 588, "offsetInEndSection": 718, "text": "Our results indicate these proteins are new factors that play important roles in the immunological pathomechanism of preeclampsia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31608721", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 156, "text": "Inflammation and oxidative stress at the maternal-fetal interface characterize the placental dysfunction that underlies the pregnancy disorder preeclampsia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32573856", "endSection": "abstract" }, { "offsetInBeginSection": 1119, "offsetInEndSection": 1265, "text": "The abnormal expression of Tim-3 on MDSC might be involved in the pathogenesis of PE, and could be a marker to evaluate the immune function in PE.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34509865", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 408, "text": "Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34599631", "endSection": "abstract" }, { "offsetInBeginSection": 130, "offsetInEndSection": 289, "text": "Disruption of well-controlled immune functions leads to infertility, placental inflammation, and numerous pregnancy complications, including preeclampsia (PE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32161574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "Effect of Endogenic and Exogenic Oxidative Stress Triggers on Adverse Pregnancy Outcomes: Preeclampsia, Fetal Growth Restriction, Gestational Diabetes Mellitus and Preterm Birth.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34576285", "endSection": "title" }, { "offsetInBeginSection": 204, "offsetInEndSection": 330, "text": "Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34847253", "endSection": "abstract" }, { "offsetInBeginSection": 1203, "offsetInEndSection": 1427, "text": "In addition, it has been demonstrated that immune disturbance may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE), recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24520479", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 265, "text": "esponse. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathophy", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29756666", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "OBJECTIVE: Increased oxidative stress and immune dysfunction are implicated in preeclampsia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21498785", "endSection": "abstract" }, { "offsetInBeginSection": 433, "offsetInEndSection": 655, "text": "r, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differentiation of T-helper cell subsets creating a cytotoxic environment in uter", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Disruption in the Regulation of Immune Responses in the Placental Subtype of Preeclampsia", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "title" }, { "offsetInBeginSection": 1654, "offsetInEndSection": 1808, "text": "a disrupted immune system might be a predisposing factor or result of placental oxidative stress or excessive inflammation in preeclampsia. Preeclampsia c", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 1247, "offsetInEndSection": 1448, "text": "clude insufficient control of inflammation, failure of tolerance toward paternal antigens at the fetal-maternal interface, and subsequent over- or insufficient activation of immune mediators. It is als", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of pre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9272206", "endSection": "abstract" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1244, "text": "s review, we focus on the role of excessive systemic inflammation as the result of a dysregulated immune system in the development of preeclampsia. These", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 161, "text": "PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of pree", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9272206", "endSection": "abstract" }, { "offsetInBeginSection": 427, "offsetInEndSection": 657, "text": "However, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differentiation of T-helper cell subsets creating a cytotoxic environment in utero.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 1639, "offsetInEndSection": 1793, "text": "In conclusion, a disrupted immune system might be a predisposing factor or result of placental oxidative stress or excessive inflammation in preeclampsia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 264, "text": "esponse. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathoph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29756666", "endSection": "abstract" }, { "offsetInBeginSection": 140, "offsetInEndSection": 385, "text": "Disruption of this immune balance and/or inadequate placental perfusion is believed to be associated with a lot of pregnancy-related complications, such as recurrent spontaneous abortion, pre-eclampsia, and fetal intrauterine growth restriction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34191338", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 530, "text": "Therefore, a delicate immune balance is critical for the maintenance of a successful pregnancy, while disruption of this balance can induce complications such as implantation failure, miscarriage, preterm birth/labor, preeclampsia and fetal growth restriction.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30058156", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 327, "text": "antigens during pregnancy. Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (P", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34847253", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 381, "text": "ccessful pregnancy. It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclamps", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27108670", "endSection": "abstract" }, { "offsetInBeginSection": 430, "offsetInEndSection": 580, "text": "ever, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9272206", "endSection": "abstract" }, { "offsetInBeginSection": 1079, "offsetInEndSection": 1323, "text": "However, immune maladaptation and hemostatic imbalance have been suggested to be responsible for adverse pregnant outcomes, such as preeclampsia (PE), miscarriage, recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19683334", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 856, "text": "PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia.METHOD OF STUDY: The serum concentrations of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) were determined by using enzyme-linked immunoadsorbent assay (ELISA) in the first trimester of pregnancy in women who had preeclampsia develop after 28 weeks of pregnancy (preeclamptic group) and in women who completed pregnancy uneventfully (control group).RESULTS: Serum concentrations of both IL-2 and TNF-alpha in the first trimester of the preeclamptic group were significantly higher than those of the control group.CONCLUSIONS: That the perturbation of feto-maternal immune regulation may precede the clinical manifestations of preeclampsia, which may be of relevance i", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9272206", "endSection": "abstract" }, { "offsetInBeginSection": 1794, "offsetInEndSection": 2009, "text": "Preeclampsia can thus be considered a hyperinflammatory state associated with defective regulation of the immune system proposed as a key element in the pathological events of the placental subtype of this disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Disruption in the Regulation of Immune Responses in the Placental Subtype of Preeclampsia.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30079067", "endSection": "title" }, { "offsetInBeginSection": 251, "offsetInEndSection": 538, "text": "It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE); hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; intrauterine growth restriction (IUGR); and recurrent spontaneous abortion (RSA).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27108670", "endSection": "abstract" } ] }, { "body": "Can autophagy related lncRNAs be used for colorectal cancer prognosis?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34692467" ], "ideal_answer": [ "Yes, a prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p < 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC." ], "exact_answer": "yes", "type": "yesno", "id": "62266c353a8413c65300008a", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34692467", "endSection": "title" }, { "offsetInBeginSection": 1347, "offsetInEndSection": 1882, "text": "A prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p < 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34692467", "endSection": "abstract" }, { "offsetInBeginSection": 2284, "offsetInEndSection": 2518, "text": "The new ARlncRNA-based model predicts CRC patient prognosis and provides new research ideas regarding potential mechanisms regulating the biological behavior of CRC. ARlncRNAs may play important roles in personalized cancer treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34692467", "endSection": "abstract" } ] }, { "body": "Are there roles for cohesin mutations in AML?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31552185" ], "ideal_answer": [ "Yes. Several landmark studies have shown that cohesin mutations perturb the balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data now begin to uncover the molecular mechanisms that underpin this phenotype. Among these mechanisms is a role for cohesin in the control of inflammatory responses in HSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and drive HSPC differentiation. Consistent with this, cohesin mutations promote resistance to inflammatory signals, and may provide a selective advantage for AML progression." ], "exact_answer": "yes", "type": "yesno", "id": "621e9aa13a8413c653000053", "snippets": [ { "offsetInBeginSection": 741, "offsetInEndSection": 1336, "text": "Several landmark studies have shown that cohesin mutations perturb the balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data now begin to uncover the molecular mechanisms that underpin this phenotype. Among these mechanisms is a role for cohesin in the control of inflammatory responses in HSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and drive HSPC differentiation. Consistent with this, cohesin mutations promote resistance to inflammatory signals, and may provide a selective advantage for AML progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31552185", "endSection": "abstract" } ] }, { "body": "What is the target of Sotorasib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34553354", "http://www.ncbi.nlm.nih.gov/pubmed/33547148", "http://www.ncbi.nlm.nih.gov/pubmed/34800654", "http://www.ncbi.nlm.nih.gov/pubmed/34504076", "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "http://www.ncbi.nlm.nih.gov/pubmed/33466360", "http://www.ncbi.nlm.nih.gov/pubmed/34520956", "http://www.ncbi.nlm.nih.gov/pubmed/34004237", "http://www.ncbi.nlm.nih.gov/pubmed/34776511", "http://www.ncbi.nlm.nih.gov/pubmed/33004338", "http://www.ncbi.nlm.nih.gov/pubmed/34607583", "http://www.ncbi.nlm.nih.gov/pubmed/34200676", "http://www.ncbi.nlm.nih.gov/pubmed/33971321", "http://www.ncbi.nlm.nih.gov/pubmed/34158284", "http://www.ncbi.nlm.nih.gov/pubmed/34715449", "http://www.ncbi.nlm.nih.gov/pubmed/34838325", "http://www.ncbi.nlm.nih.gov/pubmed/34607832", "http://www.ncbi.nlm.nih.gov/pubmed/34590053", "http://www.ncbi.nlm.nih.gov/pubmed/34558391", "http://www.ncbi.nlm.nih.gov/pubmed/34675734", "http://www.ncbi.nlm.nih.gov/pubmed/33097477", "http://www.ncbi.nlm.nih.gov/pubmed/34137282" ], "ideal_answer": [ "Sotorasib is a KRASG12C inhibitor." ], "exact_answer": [ "KRASG12C" ], "type": "factoid", "id": "61f7c60c882a024a10000025", "snippets": [ { "offsetInBeginSection": 425, "offsetInEndSection": 622, "text": "Encouragingly, the KRASG12C inhibitor AMG510 (sotorasib), which has been approved for treating NSCLC and CRC recently, makes directly targeting KRAS the most promising strategy for cancer therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34520956", "endSection": "abstract" }, { "offsetInBeginSection": 705, "offsetInEndSection": 881, "text": "Finally, we show that a selective PI4KA inhibitor augments the antineoplastic activity of the KRASG12C inhibitor\u00a0sotorasib, suggesting a clinical path to exploit this pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34504076", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 811, "text": "However, clinical candidates targeting the KRAS G12C protein have recently been developed. MRTX849 and recently approved Sotorasib are covalent binders targeting the mutated cysteine 12, occupying Switch II pocket.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34558391", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 736, "text": "Sotorasib with efficacy in kRAS-G12C mutation of NSCLC", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34553354", "endSection": "abstract" }, { "offsetInBeginSection": 725, "offsetInEndSection": 954, "text": "Two such inhibitors, sotorasib (AMG 510) and adagrasib (MRTX849), were recently evaluated in phase I-III trials for the treatment of non-small cell lung cancer with KRAS-G12C mutations, heralding a new era of precision oncology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34607583", "endSection": "abstract" }, { "offsetInBeginSection": 475, "offsetInEndSection": 616, "text": "The findings, along with data on the KRASG12C inhibitor sotorasib, were presented at the 2021 European Society for Medical Oncology Congress.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34607832", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "The FDA has approved the first KRAS-targeted therapy, sotorasib, for patients with previously treated non-small cell lung cancer with KRASG12C mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34158284", "endSection": "abstract" }, { "offsetInBeginSection": 317, "offsetInEndSection": 549, "text": "In 2021, the Food and Drug Administration (FDA) approved the use of Sotorasib (Lumakras) for the treatment of adult patients with KRAS-G12C mutated locally advanced or metastatic NSCLC, following at least one prior systemic therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34800654", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 271, "text": "The KRASG12C inhibitor sotorasib continues to impress in non-small cell lung cancer: In the phase II CodeBreak 100 trial, the agent elicited responses in more than a third of patients and led to a median progression-free survival of almost 7 months. Based on these result", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33547148", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590053", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Sotorasib is a first-in class KRASG12C covalent inhibitor in clinical development for the treatment of tumors with the KRAS p.G12C mutation. In the nonclinical to", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34004237", "endSection": "abstract" }, { "offsetInBeginSection": 81, "offsetInEndSection": 247, "text": "Recently, novel KRAS G12C inhibitors, such as sotorasib and adagrasib, are being developed in clinical trials and have revealed promising results in metastatic NSCLC.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33971321", "endSection": "abstract" }, { "offsetInBeginSection": 340, "offsetInEndSection": 509, "text": "We evaluated the clinical validity of Guardant360 CDx as a companion diagnostic for sotorasib for detection of KRAS p.G12C, an important oncogenic NSCLC driver mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34838325", "endSection": "abstract" }, { "offsetInBeginSection": 202, "offsetInEndSection": 379, "text": "Until the recent approval of sotorasib, a KRAS G12C inhibitor, lack of targeted therapy for KRAS has resulted in poor prognosis of patients with tumors harboring KRAS mutations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34715449", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Sotorasib is a first-in-class KRASG12C covalent inhibitor in clinical development for the treatment of tumors with the KR", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34137282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Sotorasib is a first-in class KRASG12C covalent inhibitor in clinical development for the treatment of tumors with the KRAS p.G12C mut", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34004237", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "Nonclinical Safety Profile of Sotorasib, a KRASG12C-Specific Covalent Inhibitor for the Treatment of KRAS p.G12C", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34137282", "endSection": "title" }, { "offsetInBeginSection": 166, "offsetInEndSection": 397, "text": "t efforts to produce subtype specific inhibitors have been more successful, and several KRASG12C inhibitors have reached clinical trials, including adagrasib and sotorasib, which have shown early evidence of efficacy in patients. L", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33466360", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. H", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34590053", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 290, "text": "phase I trial, the KRASG12C inhibitor sotorasib elicited responses in about a third of patients with the disease and was generally well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33097477", "endSection": "abstract" }, { "offsetInBeginSection": 533, "offsetInEndSection": 658, "text": "seven KRAS-G12C inhibitors are in clinical trials and sotorasib has become the first one to be granted FDA approval. Here, we", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34200676", "endSection": "abstract" }, { "offsetInBeginSection": 560, "offsetInEndSection": 800, "text": "re have been surprising advances in directly targeted drugs for KRAS, especially in KRAS (G12C) inhibitors, such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have obtained encouraging results in clinical trials. Excitingly, AMG510 w", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34776511", "endSection": "abstract" }, { "offsetInBeginSection": 435, "offsetInEndSection": 629, "text": "gly, the KRASG12C inhibitor AMG510 (sotorasib), which has been approved for treating NSCLC and CRC recently, makes directly targeting KRAS the most promising strategy for cancer therapy. To bett", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34520956", "endSection": "abstract" }, { "offsetInBeginSection": 219, "offsetInEndSection": 367, "text": "Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.METHODS: We conducted a phase 1 trial of sotorasib in patients with", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 1642, "offsetInEndSection": 1792, "text": "esults of the nonclinical safety program support a high benefit/risk ratio of sotorasib for the treatment of patients with KRAS p.G12C-mutated tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34137282", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 166, "text": "oved the first KRAS-targeted therapy, sotorasib, for patients with previously treated non-small cell lung cancer with KRASG12C mutations. In a phase I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34158284", "endSection": "abstract" }, { "offsetInBeginSection": 49, "offsetInEndSection": 199, "text": "ered an \"undruggable\" target, can be targeted successfully in non-small cell lung cancer. In a phase I trial, the KRASG12C inhibitor sotorasib elicite", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33004338", "endSection": "abstract" }, { "offsetInBeginSection": 207, "offsetInEndSection": 404, "text": "er cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.METHODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Sotorasib is a first-in-class KRASG12C covalent inhibitor in clinical development for the treatment of tumors with the KRAS p.G12C mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34137282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Sotorasib is a first-in class KRASG12C covalent inhibitor in clinical development for the treatment of tumors with the KRAS p.G12C mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34004237", "endSection": "abstract" }, { "offsetInBeginSection": 425, "offsetInEndSection": 621, "text": "Encouragingly, the KRASG12C inhibitor AMG510 (sotorasib), which has been approved for treating NSCLC and CRC recently, makes directly targeting KRAS the most promising strategy for cancer therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34520956", "endSection": "abstract" }, { "offsetInBeginSection": 352, "offsetInEndSection": 513, "text": "Based on promising results in both preclinical and clinical trials, sotorasib, a novel KRASG12C inhibitor, was given conditional approval by the FDA in May 2021.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34675734", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Nonclinical Safety Profile of Sotorasib, a KRASG12C-Specific Covalent Inhibitor for the Treatment of KRAS p.G12C-Mutated Cancer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34137282", "endSection": "title" }, { "offsetInBeginSection": 139, "offsetInEndSection": 290, "text": "In a phase I trial, the KRASG12C inhibitor sotorasib elicited responses in about a third of patients with the disease and was generally well tolerated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33097477", "endSection": "abstract" }, { "offsetInBeginSection": 1628, "offsetInEndSection": 1792, "text": "Overall, the results of the nonclinical safety program support a high benefit/risk ratio of sotorasib for the treatment of patients with KRAS p.G12C-mutated tumors.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34137282", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 60, "text": "KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32955176", "endSection": "title" } ] }, { "body": "Is ASF1 phopshorylated by the Tousled-like kinases?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/23946870", "http://www.ncbi.nlm.nih.gov/pubmed/24598821", "http://www.ncbi.nlm.nih.gov/pubmed/23869254", "http://www.ncbi.nlm.nih.gov/pubmed/20222959", "http://www.ncbi.nlm.nih.gov/pubmed/32755577" ], "ideal_answer": [ "Yes,\nAsf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-like kinases (TLKs)." ], "exact_answer": "yes", "type": "yesno", "id": "622d0aa63a8413c6530000a0", "snippets": [ { "offsetInBeginSection": 118, "offsetInEndSection": 231, "text": "Asf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-like kinases (TLKs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24598821", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The Tousled-like kinases 1 and 2 (TLK1/2) control histone deposition through the ASF1 histone chaperone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32755577", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "The Tousled-like kinases (TLKs) are involved in chromatin assembly, DNA repair, and transcription. Two TLK genes exist in humans, and their expression is often dysregulated in cancer. TLKs phosphorylate Asf1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23946870", "endSection": "abstract" }, { "offsetInBeginSection": 151, "offsetInEndSection": 264, "text": "TLKs interact specifically (and phosphorylate) with the chromatin assembly factor Asf1, a histone H3-H4 chaperone", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23869254", "endSection": "abstract" }, { "offsetInBeginSection": 183, "offsetInEndSection": 269, "text": "TLK1 substrates were identified as the histone H3 and Asf1 (a histone H3/H4 chaperone)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20222959", "endSection": "abstract" } ] }, { "body": "What is Luteolin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/18991571", "http://www.ncbi.nlm.nih.gov/pubmed/21881237", "http://www.ncbi.nlm.nih.gov/pubmed/34460026", "http://www.ncbi.nlm.nih.gov/pubmed/32407927", "http://www.ncbi.nlm.nih.gov/pubmed/30119240", "http://www.ncbi.nlm.nih.gov/pubmed/29207088", "http://www.ncbi.nlm.nih.gov/pubmed/33469821", "http://www.ncbi.nlm.nih.gov/pubmed/23317200", "http://www.ncbi.nlm.nih.gov/pubmed/29928143", "http://www.ncbi.nlm.nih.gov/pubmed/24353826", "http://www.ncbi.nlm.nih.gov/pubmed/34717250", "http://www.ncbi.nlm.nih.gov/pubmed/20074346", "http://www.ncbi.nlm.nih.gov/pubmed/22203870", "http://www.ncbi.nlm.nih.gov/pubmed/22269172", "http://www.ncbi.nlm.nih.gov/pubmed/28282295", "http://www.ncbi.nlm.nih.gov/pubmed/10972088", "http://www.ncbi.nlm.nih.gov/pubmed/24477342", "http://www.ncbi.nlm.nih.gov/pubmed/26020516", "http://www.ncbi.nlm.nih.gov/pubmed/18937165", "http://www.ncbi.nlm.nih.gov/pubmed/27185356", "http://www.ncbi.nlm.nih.gov/pubmed/27170112", "http://www.ncbi.nlm.nih.gov/pubmed/27016074", "http://www.ncbi.nlm.nih.gov/pubmed/32081041", "http://www.ncbi.nlm.nih.gov/pubmed/12027807", "http://www.ncbi.nlm.nih.gov/pubmed/30280574", "http://www.ncbi.nlm.nih.gov/pubmed/16140950", "http://www.ncbi.nlm.nih.gov/pubmed/32694396", "http://www.ncbi.nlm.nih.gov/pubmed/26246742", "http://www.ncbi.nlm.nih.gov/pubmed/31994822", "http://www.ncbi.nlm.nih.gov/pubmed/31019613" ], "ideal_answer": [ "Luteolin has been reviewed as a flavonoid possessing potential cardioprotective, anti-inflammatory, anti-cancer activities.", "Luteolin, a polyphenolic flavonoid, has potent anti-inflammatory properties." ], "exact_answer": [ "flavonoid" ], "type": "factoid", "id": "6226335d3a8413c653000082", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 185, "text": "Recently, many studies have reported the anticancer properties of flavonoid luteolin against a variety of tumors, but there is still a lack in the description of its mechanism of action", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32081041", "endSection": "abstract" }, { "offsetInBeginSection": 242, "offsetInEndSection": 319, "text": "Luteolin, a polyphenolic flavonoid, has potent anti-inflammatory properties. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32694396", "endSection": "abstract" }, { "offsetInBeginSection": 123, "offsetInEndSection": 265, "text": "Luteolin is a falconoid compound that has an antioxidant effect, but its mechanism in I/R injury in vivo and in vitro is still under explored.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34460026", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 88, "text": "Luteolin is a naturally occurring flavone that reportedly has anti-inflammatory effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27170112", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Luteolin is a flavonoid present in plants in the form of aglycone or glucosides.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30280574", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 294, "text": "Luteolin, a naturally occurring flavonoid, possesses anti-cancer activities against several human cancers, but the exact molecular and biochemical mechanisms of above findings are not very clear, and its activity against head and neck squamous cell carcinoma (HNSCC) is seldom mentioned. In thi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24477342", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 259, "text": "Luteolin is a flavonoid with antioxidant properties already demonstrated in studies related to inflammation, tumor, and cardiovascular processes; however, there are no available information regarding its antioxidant effects at the venous endothelial site. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33469821", "endSection": "abstract" }, { "offsetInBeginSection": 162, "offsetInEndSection": 258, "text": "Luteolin (3',4',5,7-tetrahydroxyflavone) is a phytochemical found frequently in medicinal herbs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32407927", "endSection": "abstract" }, { "offsetInBeginSection": 156, "offsetInEndSection": 228, "text": "Luteolin is a dietary flavonoid commonly found in some medicinal plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16140950", "endSection": "abstract" }, { "offsetInBeginSection": 223, "offsetInEndSection": 393, "text": "Luteolin (2-[3,4-dihydroxyphenyl]-5,7-dihydroxy-4-chromenone), is a naturally occurring flavonoid found in fruits and vegetables that exhibits many anticancer properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29928143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Luteolin, 3',4',5,7-tetrahydroxyflavone, is a common flavonoid that exists in many types of plants including fruits, vegetables, and medicinal herbs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991571", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Luteolin is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27016074", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 138, "text": "Luteolin is a falconoid compound that is present in various types of plants and possesses remarkable potential as a chemopreventive agent.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29207088", "endSection": "abstract" }, { "offsetInBeginSection": 75, "offsetInEndSection": 166, "text": "Luteolin is a natural flavonoid widely distributed in plants with anti-inflammatory effect.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30119240", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23317200", "endSection": "abstract" }, { "offsetInBeginSection": 149, "offsetInEndSection": 229, "text": "Luteolin is an anti-inflammatory flavonoid and widely distributed in the plants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22203870", "endSection": "abstract" }, { "offsetInBeginSection": 34, "offsetInEndSection": 184, "text": "ucial in the pathogenesis of numerous brain disorders. Luteolin, a flavonoid compound, inhibits glutamate release, however, its ability to affect glut", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27185356", "endSection": "abstract" }, { "offsetInBeginSection": 99, "offsetInEndSection": 249, "text": "depression and endoplasmic reticulum stress. Luteolin is a flavonoid contained in many plants and with a variety of known pharmacological properties s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21881237", "endSection": "abstract" }, { "offsetInBeginSection": 21, "offsetInEndSection": 171, "text": " common multiple infection disease under 2 years old. Luteolin is a natural flavonoid widely distributed in plants with anti-inflammatory effect. This", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30119240", "endSection": "abstract" }, { "offsetInBeginSection": 222, "offsetInEndSection": 360, "text": "Luteolin is a naturally occurring flavonoid with diverse pharmacological properties such as anti-inflammatory, antioxidant and anticancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28282295", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "BACKGROUND: Luteolin is a 3',4',5,7-tetrahydroxyflavone found in various fruits and", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22269172", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "Luteolin is a bioflavonoid that attenuates adipocyte-derived inflammatory responses via suppression of nuclear factor-\u03baB/mitogen-activated protein kinases pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26246742", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Background: Luteolin (3',4',5,7-tetrahydroxyflavone) is a flavone with a yellow crystalline appearance present in numerous plants such as broccoli, green chili,", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31019613", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Luteolin is a flavone which occurs in medicinal plants as well as in some vegetables and spices.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18937165", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 71, "text": "Luteolin, a flavonoid with potential for cancer prevention and therapy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18991571", "endSection": "title" }, { "offsetInBeginSection": 173, "offsetInEndSection": 563, "text": "I diabetes. Luteolin is a bioflavonoid with many beneficial properties such as antioxidant, antiproliferative, and anti-cancer.OBJECTIVES: To elucidate the potential anti-inflammatory response and the underlying mechanism of luteolin in 3T3-L1 adipocytes.MATERIALS AND METHODS: We stimulated 3T3-L1 adipocytes with the mixture of tumor necrosis factor-\u03b1, lipopolysaccharide, and interferon-", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26246742", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 84, "text": "Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12027807", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10972088", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31994822", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Luteolin is a flavonoid found in abundance in celery, green pepper, and dandelions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24353826", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 181, "text": "BACKGROUND: Luteolin, a plant derived flavonoid, exerts a variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen and nitro", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20074346", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Luteolin, a naturally occurring flavonoid, is abundant in our daily dietary intake.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12027807", "endSection": "abstract" }, { "offsetInBeginSection": 714, "offsetInEndSection": 809, "text": "The flavonoid luteolin shows therapeutic potential with low incidence of unwanted side effects.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26020516", "endSection": "abstract" }, { "offsetInBeginSection": 144, "offsetInEndSection": 370, "text": "Luteolin is a flavonoid contained in many plants and with a variety of known pharmacological properties such as anti-inflammatory, anti-anxiety, and memory-improving effects, suggesting that luteolin penetrates into the brain.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21881237", "endSection": "abstract" } ] }, { "body": "Does sphingosine-1 phosphoate suppress epiregulin?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33189864" ], "ideal_answer": [ "Sphingosine-1 phosphate induces epiregulin (EREG) gene expression." ], "exact_answer": "no", "type": "yesno", "id": "6237a6e93a8413c6530000b1", "snippets": [ { "offsetInBeginSection": 1971, "offsetInEndSection": 2128, "text": "S1P-induced FOXO1 and EREG gene expression suggests that the activation of S1P-S1PR axis may cooperate with gonadotropins in modulating follicle development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33189864", "endSection": "abstract" }, { "offsetInBeginSection": 1411, "offsetInEndSection": 1627, "text": "S1P-dependent CREB phosphorylation induced FOXO1 and the EGF-like epiregulin-encoding gene (EREG), confirming the exclusive role of gonadotropins and interleukins in this process, but did not affect steroidogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33189864", "endSection": "abstract" } ] }, { "body": "Which is the literature-based database of phenotypes?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34788791" ], "ideal_answer": [ "PheneBank is a Web-portal for retrieving human phenotype-disease associations that have been text-mined from the whole of Medline. This approach exploits state-of-the-art machine learning for concept identification by utilising an expert annotated rare disease corpus from the PMC Text Mining subset. Evaluation of the system for entities is conducted on a gold-standard corpus of rare disease sentences and for associations against the Monarch initiative data.", "PheneBank is a Web-portal for retrieving human phenotype-disease associations that have been text-mined from the whole of Medline." ], "exact_answer": [ "PheneBank" ], "type": "factoid", "id": "621e63a43a8413c653000051", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "PheneBank: a literature-based database of phenotypes.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788791", "endSection": "title" }, { "offsetInBeginSection": 312, "offsetInEndSection": 772, "text": "PheneBank is a Web-portal for retrieving human phenotype-disease associations that have been text-mined from the whole of Medline. Our approach exploits state-of-the-art machine learning for concept identification by utilising an expert annotated rare disease corpus from the PMC Text Mining subset. Evaluation of the system for entities is conducted on a gold-standard corpus of rare disease sentences and for associations against the Monarch initiative data.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34788791", "endSection": "abstract" } ] }, { "body": "Idecabtagene vicleucel can be used for treatment of which disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34461271", "http://www.ncbi.nlm.nih.gov/pubmed/34256668", "http://www.ncbi.nlm.nih.gov/pubmed/33896344", "http://www.ncbi.nlm.nih.gov/pubmed/34527606", "http://www.ncbi.nlm.nih.gov/pubmed/34625232", "http://www.ncbi.nlm.nih.gov/pubmed/33626253", "http://www.ncbi.nlm.nih.gov/pubmed/33598857", "http://www.ncbi.nlm.nih.gov/pubmed/34854741", "http://www.ncbi.nlm.nih.gov/pubmed/34104374", "http://www.ncbi.nlm.nih.gov/pubmed/34145225" ], "ideal_answer": [ "Idecabtagene vicleucel was shown to be effective for Relapsed and Refractory Multiple Myeloma." ], "exact_answer": [ "Multiple Myeloma" ], "type": "factoid", "id": "61f7ce26882a024a1000002d", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 342, "text": "B-cell maturation antigen (BCMA) has become a key target for antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T-cell therapies, and other immunotherapies in multiple myeloma. Some of these agents such as belantamab mafodotin and idecabtagene vicleucel have already received regulatory approval in the United States. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34461271", "endSection": "abstract" }, { "offsetInBeginSection": 1113, "offsetInEndSection": 1321, "text": "These include isatuximab (also anti-CD38) and, in the past year, the antibody-drug conjugate (ADC) belantamab mafodotin and the chimeric antigen receptor (CAR) T-cell product idecabtagene vicleucel (ide-cel).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34527606", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 219, "text": "Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34256668", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34145225", "endSection": "title" }, { "offsetInBeginSection": 233, "offsetInEndSection": 406, "text": "Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34145225", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33626253", "endSection": "title" }, { "offsetInBeginSection": 1917, "offsetInEndSection": 2100, "text": "CONCLUSIONS: Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33626253", "endSection": "abstract" }, { "offsetInBeginSection": 1633, "offsetInEndSection": 1822, "text": "Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34104374", "endSection": "abstract" }, { "offsetInBeginSection": 1207, "offsetInEndSection": 1632, "text": "After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34104374", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 337, "text": "BACKGROUND AND OBJECTIVE: Registrational trials for ciltacabtagene autoleucel [cilta-cel]) and idecabtagene vicleucel [ide-cel] chimeric antigen receptor T-cell (CAR-T) therapies were single-arm studies conducted with relapse refractory multiple myeloma (MM) patients who were triple-class-exposed (TCE) or triple-class-refractory (TCR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33598857", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "BACKGROUND: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33626253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 325, "text": "Idecabtagene vicleucel (ide-cel, bb2121), a chimeric antigen receptor (CAR) T cell therapy, has been investigated in patients with relapsed and refractory multiple myeloma (RRMM) who have received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody in the single-arm phase 2 KarMMa clinical trial. Two ther", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33896344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 269, "text": "BACKGROUND: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple m", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33626253", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34104374", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34104374", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 316, "text": "Idecabtagene vicleucel (ide-cel, bb2121), a chimeric antigen receptor (CAR) T cell therapy, has been investigated in patients with relapsed and refractory multiple myeloma (RRMM) who have received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody in the single-arm phase 2 KarMMa clinical trial.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33896344", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 341, "text": "Idecabtagene vicleucel (ide-cel), a novel chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), has recently gained approval by the US FDA for relapsed and refractory multiple myeloma (RRMM) after multicenter trials have demonstrated unprecedented results in this difficult-to-treat subgroup of patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34854741", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34854741", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 392, "text": "BACKGROUND: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma.METHODS: In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed an", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33626253", "endSection": "abstract" }, { "offsetInBeginSection": 499, "offsetInEndSection": 886, "text": "The bulk of CAR T-cell constructs currently in clinical development target the B-cell maturation antigen (BCMA) and to date only idecabtagene vicleucel (ide-cel) is approved by the Food and Drug Administration (FDA) for commercial use in adult patients with relapsed or refractory MM based on the promising clinical responses and positive safety record shown in the pivotal KarMMa study.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34625232", "endSection": "abstract" }, { "offsetInBeginSection": 233, "offsetInEndSection": 405, "text": "Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34145225", "endSection": "abstract" } ] }, { "body": "LINC00339 is a diagnostic, prognostic and treatment efficacy biomarker for what disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31239716", "http://www.ncbi.nlm.nih.gov/pubmed/31269584", "http://www.ncbi.nlm.nih.gov/pubmed/28171565", "http://www.ncbi.nlm.nih.gov/pubmed/34741346", "http://www.ncbi.nlm.nih.gov/pubmed/31188482", "http://www.ncbi.nlm.nih.gov/pubmed/31128030", "http://www.ncbi.nlm.nih.gov/pubmed/34105151", "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "http://www.ncbi.nlm.nih.gov/pubmed/32991297", "http://www.ncbi.nlm.nih.gov/pubmed/31081143", "http://www.ncbi.nlm.nih.gov/pubmed/29499931", "http://www.ncbi.nlm.nih.gov/pubmed/30485513", "http://www.ncbi.nlm.nih.gov/pubmed/29906749", "http://www.ncbi.nlm.nih.gov/pubmed/32308105", "http://www.ncbi.nlm.nih.gov/pubmed/33235461", "http://www.ncbi.nlm.nih.gov/pubmed/31781497" ], "ideal_answer": [ "LINC00339 as a cancer diagnostic, prognostic and treatment efficacy biomarker." ], "exact_answer": [ "cancer" ], "type": "factoid", "id": "623345bf3a8413c6530000ab", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Long noncoding RNA Linc00339 promotes triple-negative breast cancer progression through miR-377-3p/HOXC6 signaling pathway.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "title" }, { "offsetInBeginSection": 122, "offsetInEndSection": 204, "text": "Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "PURPOSE: To investigate the role and mechanism of long non-coding (lnc) RNA LINC00339 in pancreatic cancer (PANC), and provided a potential target for its biological diagnosis and trea", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31128030", "endSection": "abstract" }, { "offsetInBeginSection": 276, "offsetInEndSection": 417, "text": " showed that LINC00339 was significantly up-regulated in NSCLC tissue and cells, which indicated the poor prognosis of NSCLC patients. Loss-o", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29906749", "endSection": "abstract" }, { "offsetInBeginSection": 139, "offsetInEndSection": 232, "text": "(HCC). The lncRNA LINC00339 was reported to regulate the development of lung cancer or breast", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31239716", "endSection": "abstract" }, { "offsetInBeginSection": 270, "offsetInEndSection": 372, "text": "we demonstrated that LINC00339 was upregulated in glioma tissue as well as in glioma cell lines. The e", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29499931", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 99, "text": "LINC00339 promotes cell proliferation and metastasis in pancreatic cancer via miR-497-5p/IGF1R axis", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31128030", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 227, "text": "Introduction: Accumulating evidence has indicated that long noncoding RNAs (lncRNAs) are pivotal regulators involved in the pathogenesis of cancer; however, the molecular mechanism of LINC00339 in colorectal cancer (CRC) remain", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33235461", "endSection": "abstract" }, { "offsetInBeginSection": 635, "offsetInEndSection": 805, "text": "vasion. Xenograft experiment was used to test tumor growth in vivo. Results: LINC00339 overexpression was correlated with an advanced stage, metastasis, and bad prognosis", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31239716", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Endometriosis risk alleles at 1p36.12 act through inverse regulation of CDC42 and LINC00339", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28171565", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "LINC00339 regulates ROCK1 by miR-152 to promote cell proliferation and migration in hepatocellular carcinoma", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31081143", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "Long noncoding RNA Linc00339 promotes triple-negative breast cancer progression through miR-377-3p/HOXC6 signaling pathway", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "title" }, { "offsetInBeginSection": 126, "offsetInEndSection": 208, "text": "ugh microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 1063, "offsetInEndSection": 1249, "text": " in vivo experiments, Linc00339 overexpression promoted triple-negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis. Silencing of Linc00339 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 211, "offsetInEndSection": 339, "text": "pared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 700, "text": "work identified a 5-lncRNA signature (ENSG00000206567, PCAT29, ENSG00000257989, LOC388282, and LINC00339) from TCGA training studies (n = 1,878). The identifie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32991297", "endSection": "abstract" }, { "offsetInBeginSection": 341, "offsetInEndSection": 426, "text": "fects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3-(4", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 348, "offsetInEndSection": 459, "text": "LINC00339 expression in colorectal cancer tissues and adjacent colorectal sampleswas detected by Real-time PCR.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269584", "endSection": "abstract" }, { "offsetInBeginSection": 541, "offsetInEndSection": 628, "text": "Linc00339 was then found to play a critical role in Huaier-mediated cancer suppression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31781497", "endSection": "abstract" }, { "offsetInBeginSection": 2169, "offsetInEndSection": 2306, "text": "Conclusions: LINC00339 expression is upregulated in colorectal cancer tissues and correlated with patients' clinicopathological features.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31269584", "endSection": "abstract" }, { "offsetInBeginSection": 839, "offsetInEndSection": 937, "text": "tween miR-152 and ROCK1. The role of LINC00339 in tumor formation and metastasis were explored thr", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31081143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 327, "text": "PURPOSE: To investigate the role and mechanism of long non-coding (lnc) RNA LINC00339 in pancreatic cancer (PANC), and provided a potential target for its biological diagnosis and treatment.METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00339 in PANC tissue specime", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31128030", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31188482", "endSection": "title" }, { "offsetInBeginSection": 1486, "offsetInEndSection": 1689, "text": "Our findings highlight the importance of the LINC00339-miR-539-SOX9 pathway in gastric cancer pathogenesis and may point to novel targets for the diagnosis, prognosis, and/or treatment of gastric cancer.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32308105", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "LINC00339 promotes cell proliferation and metastasis in pancreatic cancer via miR-497-5p/IGF1R axis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31128030", "endSection": "title" }, { "offsetInBeginSection": 783, "offsetInEndSection": 900, "text": "In conclusion, LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31188482", "endSection": "abstract" }, { "offsetInBeginSection": 1276, "offsetInEndSection": 1514, "text": "r transfected with miR-152 mimics. LINC00339 exerted oncogenesis effect on HCC progression by targeting miR-152/ROCK1, and the expression of LINC00339 was negatively correlated with miR-152 expression and positively correlated with ROCK1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31081143", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "Long noncoding RNA LINC00339 promotes the oncogenicity of gastric cancer by regulating SRY-box 9 expression via sponging of microRNA-539.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32308105", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Long noncoding RNA LINC00339 promotes laryngeal squamous cell carcinoma cell proliferation and invasion via sponging miR-145.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30485513", "endSection": "title" }, { "offsetInBeginSection": 1762, "offsetInEndSection": 1954, "text": "In conclusion, our results illuminated that the novel Linc00339/miR-377-3p/HOXC6 axis played a critical role in TNBC progression and might be a promising therapeutic target for TNBC treatment.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 1043, "offsetInEndSection": 1225, "text": "Through in vitro and in vivo experiments, Linc00339 overexpression promoted triple-negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 949, "offsetInEndSection": 1042, "text": "Linc00339 was increased in breast cancer cell lines compared with the normal epithelial cell.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 1609, "offsetInEndSection": 1714, "text": "And miR-377-3p was involved in Linc00339-mediated TNBC proliferation through regulating HOXC6 expression.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 122, "text": "The SP1-Induced Long Noncoding RNA, LINC00339, Promotes Tumorigenesis in Colorectal Cancer via the miR-378a-3p/MED19 Axis.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33235461", "endSection": "title" }, { "offsetInBeginSection": 205, "offsetInEndSection": 334, "text": "We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30618083", "endSection": "abstract" } ] }, { "body": "What is the role of PCAT6 in human cancers?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31676070", "http://www.ncbi.nlm.nih.gov/pubmed/34885209" ], "ideal_answer": [ "PCAT6, is a carcinogenic lncRNA. It is abnormally elevated in various human malignant tumors. PCAT6 has been found to sponge various miRNAs to activate the signaling pathways, which further affects tumor cell proliferation, migration, invasion, cycle, apoptosis, radioresistance, and chemoresistance. It is believed to have diagnostic and prognostic value and clinical applications in various human malignancies." ], "type": "summary", "id": "622669363a8413c653000089", "snippets": [ { "offsetInBeginSection": 92, "offsetInEndSection": 164, "text": "LncRNA PCAT6 was involved in the progression of multiple human cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31676070", "endSection": "abstract" }, { "offsetInBeginSection": 77, "offsetInEndSection": 814, "text": "Emerging evidence has shown that PCAT6, a newly discovered carcinogenic lncRNA, is abnormally elevated in various human malignant tumors. Until now, PCAT6 has been found to sponge various miRNAs to activate the signaling pathways, which further affects tumor cell proliferation, migration, invasion, cycle, apoptosis, radioresistance, and chemoresistance. Moreover, PCAT6 has been shown to exert biological functions beyond ceRNAs. In this review, we summarize the biological characteristics of PCAT6 in a variety of human malignancies and describe the biological mechanisms by which PCAT6 can facilitate tumor progression. Finally, we discuss its diagnostic and prognostic values and clinical applications in various human malignancies.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34885209", "endSection": "abstract" } ] }, { "body": "Can whole genome sequencing be used for diagnosis of mitochondrial disease?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34732400" ], "ideal_answer": [ "Yes. Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments." ], "exact_answer": "yes", "type": "yesno", "id": "62068e67c9dfcb9c09000038", "snippets": [ { "offsetInBeginSection": 1410, "offsetInEndSection": 1893, "text": "Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34732400", "endSection": "abstract" } ] }, { "body": "What are the targets of avapritinib?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30274985", "http://www.ncbi.nlm.nih.gov/pubmed/32615108", "http://www.ncbi.nlm.nih.gov/pubmed/31117741", "http://www.ncbi.nlm.nih.gov/pubmed/33465704", "http://www.ncbi.nlm.nih.gov/pubmed/33876372", "http://www.ncbi.nlm.nih.gov/pubmed/33025950", "http://www.ncbi.nlm.nih.gov/pubmed/34343033", "http://www.ncbi.nlm.nih.gov/pubmed/34580817", "http://www.ncbi.nlm.nih.gov/pubmed/32100250", "http://www.ncbi.nlm.nih.gov/pubmed/29233825", "http://www.ncbi.nlm.nih.gov/pubmed/34023541", "http://www.ncbi.nlm.nih.gov/pubmed/33307872", "http://www.ncbi.nlm.nih.gov/pubmed/33453089", "http://www.ncbi.nlm.nih.gov/pubmed/34552008", "http://www.ncbi.nlm.nih.gov/pubmed/32821296", "http://www.ncbi.nlm.nih.gov/pubmed/33301227", "http://www.ncbi.nlm.nih.gov/pubmed/32972961" ], "ideal_answer": [ "Avapritinib is a novel inhibitor of KIT/PDGFRA. It is approved in the U.S. for the treatment of adults with PDGFRA exon 18-mutant unresectable or metastatic gastrointestinal stromal tumors." ], "exact_answer": [ [ "KIT" ], [ "PDGFRA" ] ], "type": "list", "id": "61f7d535882a024a10000034", "snippets": [ { "offsetInBeginSection": 673, "offsetInEndSection": 807, "text": "In vitro studies tested the efficacy of MRP-1 inhibitors (nilotinib, ripretinib, selumetinib, and avapritinib) in sarcoma cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34552008", "endSection": "abstract" }, { "offsetInBeginSection": 338, "offsetInEndSection": 649, "text": "In this review, we briefly outline the history of treatment for systemic mastocytosis and subsequently focus on the clinical development and potential applications of avapritinib (previously known as BLU-285), a potent and selective oral inhibitor of the tyrosine kinase most commonly mutated in this condition.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34580817", "endSection": "abstract" }, { "offsetInBeginSection": 164, "offsetInEndSection": 401, "text": "Avapritinib is a novel, potent KIT/PDGFRA inhibitor with substantial clinical activity in patients with the D842V genotype. To date, only a minority of PDGFRA-mutant patients treated with avapritinib have developed secondary resistance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32972961", "endSection": "abstract" }, { "offsetInBeginSection": 1095, "offsetInEndSection": 1382, "text": "Clearly, better knowledge of the molecular mechanisms underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine kinase inhibitors such as avapritinib and ripretinib will provide new individualized therapeutic strategies for GIST patients.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33307872", "endSection": "abstract" }, { "offsetInBeginSection": 210, "offsetInEndSection": 453, "text": "NAVIGATOR is a two-part, single-arm, dose escalation and expansion study designed to evaluate safety and antineoplastic activity of avapritinib, a selective, potent inhibitor of KIT and PDGFRA, in patients with unresectable or metastatic GIST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33453089", "endSection": "abstract" }, { "offsetInBeginSection": 1624, "offsetInEndSection": 1778, "text": "CONCLUSION: Targeting PDGFRA D842V-mutant GIST with avapritinib resulted in an unprecedented, durable clinical benefit, with a manageable safety profile. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33465704", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 209, "text": "BACKGROUND: Avapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18-mutant unresectable or metastatic gastrointestinal stromal tumors (U/M GISTs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33301227", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 165, "text": "Avapritinib (AYVAKIT\u2122) is a potent and selective tyrosine kinase inhibitor of platelet-derived growth factor receptor alpha (PDGFRA) and KIT activation loop mutants.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32100250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "Avapritinib is a protein kinase inhibitor designed to selectively inhibit oncogenic KIT and platelet-derived growth factor receptor alpha (PDGFRA) mutants by targeting the active conformation of the kinase.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34023541", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 194, "text": "In a phase I trial of avapritinib (formerly BLU-285), which targets D816V mutant KIT, for the treatment of advanced systemic mastocytosis, patients experienced rapid and durable disease control.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233825", "endSection": "abstract" }, { "offsetInBeginSection": 566, "offsetInEndSection": 840, "text": "In this study, we discovered that avapritinib (BLU-285), a potent, selective, and orally bioavailable tyrosine kinase inhibitor against mutant forms of KIT and platelet-derived growth factor receptor alpha (PDGFRA), attenuates the transport function of both ABCB1 and ABCG2.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31117741", "endSection": "abstract" }, { "offsetInBeginSection": 314, "offsetInEndSection": 482, "text": "Avapritinib is approved in the USA for PDGFRA exon 18 (including D842V) mutant GIST and is undergoing regulatory assessment in the USA as a 4th-line treatment for GIST.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32100250", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 284, "text": "Avapritinib is a tyrosine kinase inhibitor (TKI) that has recently received Food and Drug Administration (FDA) approval for the treatment of metastatic or unresectable gastrointestinal stromal tumors harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33025950", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Avapritinib: A Selective Inhibitor of KIT and PDGFR\u03b1 that Reverses ABCB1 and ABCG2-Mediated Multidrug Resistance in Cancer Cell Lines.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31117741", "endSection": "title" }, { "offsetInBeginSection": 563, "offsetInEndSection": 911, "text": "y, United States Federal and Drug Administration (FDA) approved two new tyrosine kinase inhibitors for the treatment of heavily pretreated advanced/unresectable GIST including avapritinib (a selective inhibitor for PDGFRA exon 18 mutation including D842V mutations) and ripretinib (a broad-spectrum kinase inhibitor of c-Kit and PDGFRA). In this ar", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33876372", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "In a phase I trial of avapritinib (formerly BLU-285), which targets D816V mutant KIT, for the treatment of advanced systemic mastocytosis, patients experienced rapid and durable disease control. Th", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29233825", "endSection": "abstract" }, { "offsetInBeginSection": 231, "offsetInEndSection": 547, "text": "ibitors. We aimed to assess the safety, tolerability, and antitumour activity of avapritinib, a novel KIT and PDGFRA inhibitor that potently inhibits PDGFRA D842V, in patients with advanced gastrointestinal stromal tumours, including patients with KIT and PDGFRA D842V-mutant gastrointestinal stromal tumours (NAVIGA", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32615108", "endSection": "abstract" }, { "offsetInBeginSection": 574, "offsetInEndSection": 854, "text": "study, we discovered that avapritinib (BLU-285), a potent, selective, and orally bioavailable tyrosine kinase inhibitor against mutant forms of KIT and platelet-derived growth factor receptor alpha (PDGFRA), attenuates the transport function of both ABCB1 and ABCG2. Moreover, ava", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31117741", "endSection": "abstract" }, { "offsetInBeginSection": 161, "offsetInEndSection": 284, "text": "V. Avapritinib is a novel, potent KIT/PDGFRA inhibitor with substantial clinical activity in patients with the D842V genoty", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32972961", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Avapritinib is a tyrosine kinase inhibitor (TKI) that has recently received Food and Drug Administration (FDA) approval for the treatment of metastatic or unresectable gastrointestinal stromal tumors harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. Muta", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33025950", "endSection": "abstract" }, { "offsetInBeginSection": 177, "offsetInEndSection": 254, "text": "(GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34343033", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "BACKGROUND: Avapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18-mutant unresectable or metastatic gastrointestinal stromal tumors ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33301227", "endSection": "abstract" }, { "offsetInBeginSection": 448, "offsetInEndSection": 793, "text": "Herein, we report a clinical case of a patient with metastatic vulvar melanoma, harboring an exon 17 c-KIT mutation, treated with avapritinib (BLU-285) - a highly potent and selective oral kinase inhibitor designed to treat imatinib-resistant gastro-intestinal stromal tumors (GIST) by targeting KIT/PDGFR\u03b1 activation loop mutants (exons 17/18).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32821296", "endSection": "abstract" }, { "offsetInBeginSection": 297, "offsetInEndSection": 756, "text": "utation. We tested the activity of avapritinib, a potent and highly selective inhibitor of mutated KIT and PDGFRA, in three patient-derived xenograft (PDX) GIST models carrying different KIT mutations, with differential sensitivity to standard TKI.Experimental Design: NMRI nu/nu mice (n = 93) were transplanted with human GIST xenografts with KIT exon 11+17 (UZLX-GIST9 KIT 11+17 ), exon 11 (UZLX-GIST3 KIT 11 ), or exon 9 (UZLX-GIST2B KIT9 ) mutations, resp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30274985", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 755, "text": "inhibitors. We aimed to assess the safety, tolerability, and antitumour activity of avapritinib, a novel KIT and PDGFRA inhibitor that potently inhibits PDGFRA D842V, in patients with advanced gastrointestinal stromal tumours, including patients with KIT and PDGFRA D842V-mutant gastrointestinal stromal tumours (NAVIGATOR).METHODS: NAVIGATOR is a two-part, open-label, dose-escalation and dose-expansion, phase 1 study done at 17 sites across nine countries (Belgium, France, Germany, Poland, Netherlands, South Korea, Spain, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32615108", "endSection": "abstract" } ] }, { "body": "What is Jackhammer esophagus?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/27274539", "http://www.ncbi.nlm.nih.gov/pubmed/32510747", "http://www.ncbi.nlm.nih.gov/pubmed/32601779", "http://www.ncbi.nlm.nih.gov/pubmed/33337637", "http://www.ncbi.nlm.nih.gov/pubmed/29521727", "http://www.ncbi.nlm.nih.gov/pubmed/27660053", "http://www.ncbi.nlm.nih.gov/pubmed/33043556", "http://www.ncbi.nlm.nih.gov/pubmed/30543463", "http://www.ncbi.nlm.nih.gov/pubmed/27458179", "http://www.ncbi.nlm.nih.gov/pubmed/23452629", "http://www.ncbi.nlm.nih.gov/pubmed/30941328", "http://www.ncbi.nlm.nih.gov/pubmed/29667413", "http://www.ncbi.nlm.nih.gov/pubmed/25961439", "http://www.ncbi.nlm.nih.gov/pubmed/34001027", "http://www.ncbi.nlm.nih.gov/pubmed/34642274", "http://www.ncbi.nlm.nih.gov/pubmed/29967357", "http://www.ncbi.nlm.nih.gov/pubmed/26927491" ], "ideal_answer": [ "Jackhammer esophagus (JE) is a hypercontractile esophageal motor disorder defined by at least two swallows with a distal contractile integral (DCI) >8000 mm Hg.s.cm during high-resolution manometry (HRM).", "Jackhammer esophagus (JE) is a recently recognized esophageal motility disorder that is characterized by hypercontractile peristalsis." ], "type": "summary", "id": "622cbec13a8413c65300009b", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Jackhammer esophagus (JE) is a recently recognized esophageal motility disorder that is characterized by hypercontractile peristalsis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33337637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Hypercontractile esophagus (HE), also known as jackhammer esophagus, is an esophageal motility disorder.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33043556", "endSection": "abstract" }, { "offsetInBeginSection": 16, "offsetInEndSection": 221, "text": " Jackhammer esophagus (JE) is a hypercontractile esophageal motor disorder defined by at least two swallows with a distal contractile integral (DCI) >8000\u00a0mm\u00a0Hg.s.cm during high-resolution manometry (HRM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32510747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 111, "text": "Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30543463", "endSection": "abstract" }, { "offsetInBeginSection": 72, "offsetInEndSection": 325, "text": "Jackhammer esophagus (JE), a novel hypercontractile disorder associated with progression to achalasia and limited outcomes following anti-reflux surgery in patients with typical symptoms of GERD and responsiveness to proton pump inhibitor (PPI) therapy.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29967357", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Nutcracker esophagus and jackhammer esophagus are largely unknown motility disorders, also sometimes called hypertensive and hypercontractile peristalsis, respectively.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25961439", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Jackhammer esophagus is a rare esophageal motility disorder that can result in dysphagia, chest pain, and gastro-esophageal reflux symptoms.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34001027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 81, "text": "Two Distinct Types of Hypercontractile Esophagus: Classic and Spastic Jackhammer.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458179", "endSection": "title" }, { "offsetInBeginSection": 441, "offsetInEndSection": 630, "text": "The diagnosis of jackhammer esophagus as a primary motility disorder is based on the characteristic manometric findings after ruling out mechanical obstruction and eosinophilic esophagitis.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452629", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "The jackhammer esophagus is a rare hypercontractile disorder and diagnosis is based on high-resolution manometry.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29667413", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 248, "text": "Jackhammer esophagus is also rare, is characterized by esophageal hypercontraction, and comprises 4.1% of esophageal motility disorders.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32601779", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Background: Jackhammer esophagus is a hypercontractile esophageal disorder recently brought to light with the advent of high resolution manometry (HRM).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30941328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "BACKGROUND AND STUDY AIMS: With the success of peroral endoscopic myotomy (POEM) in treatment of achalasia, its successful application to other spastic esophageal motility disorders such as Jackhammer es", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27274539", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification. Res", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27458179", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "BACKGROUND: Jackhammer esophagus is a rare esophageal motility disorder that can result in dysphagia, chest pain, and gastro-esophageal reflux s", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34001027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Background: Jackhammer esophagus is a hypercontractile esophageal disorder recently brought to light with the advent of high resolution manomet", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30941328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Background/Aims: Jackhammer esophagus is an uncommon heterogeneous motility disorder associated with a distal contractile integral > 80", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34642274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "Hypercontractile esophagus (HE), also known as jackhammer esophagus, is an esophageal motility disorder. Nowa", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33043556", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 112, "text": "BACKGROUND: Jackhammer Esophagus is defined as intact esophageal peristaltic contractions with extremely elevate", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "Background: Jackhammer esophagus is a hypercontractile esophageal disorder recently brought to light with the advent of high resolution mano", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30941328", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "BACKGROUND: Jackhammer Esophagus is defined as intact esophageal peristaltic contractions with extremely elevated", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 204, "text": "BACKGROUND/AIMS: Jackhammer esophagus (JE) is a hypercontractile esophageal motor disorder defined by at least two swallows with a distal contractile integral (DCI) >8000\u00a0mm\u00a0Hg.s.cm during high-resolution", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32510747", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 267, "text": "BACKGROUND: Jackhammer esophagus (JE) is a rare esophageal motility disorder defined in the Chicago Classification of Esophageal Motility by presence of excessively high distal contractile integral (DCI) on high-resolution manometry (HRM), with unknown natural manome", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27660053", "endSection": "abstract" }, { "offsetInBeginSection": 1431, "offsetInEndSection": 1579, "text": "y and a high relapse rate.CONCLUSION: Jackhammer esophagus is a rare motility disorder. Diagnostic workup is heterogeneous and should be standardize", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32510747", "endSection": "abstract" }, { "offsetInBeginSection": 569, "offsetInEndSection": 866, "text": "dies with a diagnosis of jackhammer esophagus, hypercontractile esophagus, nutcracker, esophagogastric junction outflow obstruction, or hypertensive lower esophageal sphincter were reread using Chicago Classification version 3.0, and were included if they met criteria for jackhammer esophagus. Un", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29521727", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Frequency of Jackhammer Esophagus as the Extreme Phenotypes of Esophageal Hypercontractility Based on the New Chicago Classification.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927491", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 124, "text": "BACKGROUND: Jackhammer Esophagus is defined as intact esophageal peristaltic contractions with extremely elevated amplitudes", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927491", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: Jackhammer esophagus is a rare esophageal motility disorder that can result in dysphagia, chest pain, and gastro-esophageal reflux symptoms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34001027", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Background/Aims: Jackhammer esophagus is an uncommon heterogeneous motility disorder associated with a distal contractile integral > ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34642274", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "BACKGROUND: Jackhammer esophagus is a rare esophageal motility disorder that can result in dysphagia, chest pain, and gastro-esophageal refl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34001027", "endSection": "abstract" }, { "offsetInBeginSection": 114, "offsetInEndSection": 368, "text": "amplitudes. We conducted a retrospective study to identify the frequency of esophageal hypercontractility and the clinical characteristics of Jackhammer Esophagus.METHODS: Charts for the patients referred for manometric study at a tertiary-care motility ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26927491", "endSection": "abstract" }, { "offsetInBeginSection": 262, "offsetInEndSection": 328, "text": "whereas jackhammer esophagus is associated with hypercontractility", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23452629", "endSection": "abstract" } ] }, { "body": "Can METTL3 methylate long noncoding RNAs?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/34505967" ], "ideal_answer": [ "Yes, METTL3 can modulate methylation and expression of lncRNA." ], "exact_answer": "yes", "type": "yesno", "id": "622662e13a8413c653000085", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "METTL3-Mediated lncRNA m6A Modification in the Osteogenic Differentiation of Human Adipose-Derived Stem Cells Induced by NEL-Like 1 Protein.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34505967", "endSection": "title" }, { "offsetInBeginSection": 12, "offsetInEndSection": 290, "text": "This study aimed to explore the regulatory mechanism of methyltransferase3 (METTL3) -mediated long non-coding RNA (lncRNA) N6-methyladenosine (m6A) modification in the osteogenic differentiation of human adipose-derived stem cells (hASCs) induced by NEL-like 1 protein (NELL-1).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34505967", "endSection": "abstract" }, { "offsetInBeginSection": 1918, "offsetInEndSection": 2129, "text": "This study shows, for the first time, that METTL3 can activate the MAPK signaling pathway by regulating the m6A modification and expression of a lncRNA, thereby enhancing the osteogenic differentiation of hASCs.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34505967", "endSection": "abstract" } ] }, { "body": "Which disease is caused by repeat expansion in VWA1?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/33559681" ], "ideal_answer": [ "An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy." ], "exact_answer": [ "Recessive hereditary motor neuropathy" ], "type": "factoid", "id": "61f86c03882a024a10000044", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33559681", "endSection": "title" }, { "offsetInBeginSection": 2510, "offsetInEndSection": 3068, "text": "In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33559681", "endSection": "abstract" } ] }, { "body": "What is the use of the Apfel Score?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/32415631", "http://www.ncbi.nlm.nih.gov/pubmed/31230771", "http://www.ncbi.nlm.nih.gov/pubmed/34067551", "http://www.ncbi.nlm.nih.gov/pubmed/27902493", "http://www.ncbi.nlm.nih.gov/pubmed/17236637", "http://www.ncbi.nlm.nih.gov/pubmed/33683710", "http://www.ncbi.nlm.nih.gov/pubmed/33250474", "http://www.ncbi.nlm.nih.gov/pubmed/33832577", "http://www.ncbi.nlm.nih.gov/pubmed/34041090", "http://www.ncbi.nlm.nih.gov/pubmed/11861340", "http://www.ncbi.nlm.nih.gov/pubmed/34782501", "http://www.ncbi.nlm.nih.gov/pubmed/33721198" ], "ideal_answer": [ "The Apfel simplified risk score, developed in 1999, is the most widely used tool for risk stratification of postoperative nausea and vomiting." ], "type": "summary", "id": "6200839bc9dfcb9c0900001d", "snippets": [ { "offsetInBeginSection": 525, "offsetInEndSection": 1003, "text": "For PONV, anesthesia duration and Apfel score were independent risk factors.CONCLUSIONS: Our results indicate that desflurane was the main cause of ePONV. However, during the delayed phase, a higher Apfel score was the strongest predictor. In the early and delayed phases, long anesthesia duration was associated with high risk of PONV. Thus, prolonged anesthesia and desflurane use should be avoided for patients at high risk of PONV, particularly those with high Apfel scores.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33250474", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Interpretation of the four risk factors for postoperative nausea and vomiting in the Apfel simplified risk score: an analysis of published studies.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33721198", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "PURPOSE: The Apfel simplified risk score, developed in 1999, is the most widely used tool for risk stratification of postoperative nausea and vomiting (PONV). I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33721198", "endSection": "abstract" }, { "offsetInBeginSection": 1297, "offsetInEndSection": 1465, "text": "CONCLUSIONS: Significant variation exists in how the Apfel risk factors are defined and applied in PONV research, particularly with respect to postoperative opioid use.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33721198", "endSection": "abstract" }, { "offsetInBeginSection": 268, "offsetInEndSection": 449, "text": "METHODS: One hundred and twenty patients undergoing laparoscopic surgeries having 2 or more risk factors for PONV (simplified Apfel score) were randomised into 2 groups of 60 each. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33683710", "endSection": "abstract" }, { "offsetInBeginSection": 650, "offsetInEndSection": 762, "text": "In univariate analysis, female sex and Apfel scores of 2, 3, and 4 were associated with a higher POV incidence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34067551", "endSection": "abstract" }, { "offsetInBeginSection": 870, "offsetInEndSection": 1004, "text": "In multivariate logistic regression, sex, age, Apfel score, and intraoperative crystalloid infusion rate were POV predictive factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34067551", "endSection": "abstract" }, { "offsetInBeginSection": 594, "offsetInEndSection": 716, "text": "We used the Apfel scoring system for evaluation of risk of post-operative nausea and vomiting (PONV) for each participant.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34041090", "endSection": "abstract" }, { "offsetInBeginSection": 282, "offsetInEndSection": 501, "text": "THODS: Adult inpatients undergoing elective surgery during general anesthesia and having at least two of the four Apfel risk factors for postoperative nausea and vomiting were enrolled at 9 U.S. and 10 European sites. A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/27902493", "endSection": "abstract" }, { "offsetInBeginSection": 142, "offsetInEndSection": 241, "text": "The Apfel Simplified Score is an evidence-based instrument for determining individual risk of PONV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33832577", "endSection": "abstract" }, { "offsetInBeginSection": 112, "offsetInEndSection": 236, "text": "The simplified Apfel score is an attractive and frequently used tool to assess PONV risk in the general surgical population.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32415631", "endSection": "abstract" }, { "offsetInBeginSection": 1086, "offsetInEndSection": 1178, "text": "The Apfel score is an evidence-based tool that providers can use to reduce the risk of PONV.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33832577", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "PURPOSE: The Apfel simplified risk score, developed in 1999, is the most widely used tool for risk stratification of postoperative nausea and vomiting (PONV).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33721198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Preventing Nausea and Vomiting After Bariatric Surgery: Is the Apfel Risk Prediction Score Enough to Guide Prophylaxis?", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32415631", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 150, "text": "PURPOSE: The Apfel simplified risk score, developed in 1999, is the most widely used tool for risk stratification of postoperative nausea and vomiting", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33721198", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 153, "text": "Background: Simplified risk models, such as the Apfel score, have been developed to calculate the risk of postoperative nausea-vomiting (PONV) for adult ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34782501", "endSection": "abstract" }, { "offsetInBeginSection": 115, "offsetInEndSection": 238, "text": " simplified Apfel score is an attractive and frequently used tool to assess PONV risk in the general surgical population. D", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32415631", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Apfel's simplified score may favourably predict the risk of postoperative nausea and vomiting.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11861340", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Postoperative nausea and vomiting (PONV) : usefulness of the Apfel-score for identification of high risk patients for PONV.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17236637", "endSection": "title" }, { "offsetInBeginSection": 1066, "offsetInEndSection": 1216, "text": "dansetron returned. The Apfel score is an evidence-based tool that providers can use to reduce the risk of PONV. This electronic tool and the reminder", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33832577", "endSection": "abstract" }, { "offsetInBeginSection": 10, "offsetInEndSection": 160, "text": ": Simplified risk models, such as the Apfel score, have been developed to calculate the risk of postoperative nausea-vomiting (PONV) for adult patient", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34782501", "endSection": "abstract" }, { "offsetInBeginSection": 172, "offsetInEndSection": 340, "text": " The simplified Apfel-score includes the four factors female gender, no smoking, postoperative use of opioides and previous PONV or motion-sickness in patients' history", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17236637", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "A common predictive measure of postoperative nausea and vomiting (PONV) is the Apfel score.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31230771", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "PURPOSE: The Apfel simplified risk score, developed in 1999, is the most widely used tool for risk stratification of postoperative nausea and vomitin", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33721198", "endSection": "abstract" } ] }, { "body": "Is PPROM a condition that occurs in males or females?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/22506729", "http://www.ncbi.nlm.nih.gov/pubmed/23179796", "http://www.ncbi.nlm.nih.gov/pubmed/29727785", "http://www.ncbi.nlm.nih.gov/pubmed/30957602", "http://www.ncbi.nlm.nih.gov/pubmed/23599878", "http://www.ncbi.nlm.nih.gov/pubmed/10838338", "http://www.ncbi.nlm.nih.gov/pubmed/31018725", "http://www.ncbi.nlm.nih.gov/pubmed/24304137", "http://www.ncbi.nlm.nih.gov/pubmed/15703979", "http://www.ncbi.nlm.nih.gov/pubmed/18301713", "http://www.ncbi.nlm.nih.gov/pubmed/31272257", "http://www.ncbi.nlm.nih.gov/pubmed/21749283", "http://www.ncbi.nlm.nih.gov/pubmed/31402735", "http://www.ncbi.nlm.nih.gov/pubmed/15329560", "http://www.ncbi.nlm.nih.gov/pubmed/31372118", "http://www.ncbi.nlm.nih.gov/pubmed/16118716", "http://www.ncbi.nlm.nih.gov/pubmed/24840939", "http://www.ncbi.nlm.nih.gov/pubmed/29373884", "http://www.ncbi.nlm.nih.gov/pubmed/24175963", "http://www.ncbi.nlm.nih.gov/pubmed/23573382", "http://www.ncbi.nlm.nih.gov/pubmed/22706240" ], "ideal_answer": [ "Preterm premature rupture of fetal membranes (PPROM) occurs in pregnant females." ], "exact_answer": [ "Females" ], "type": "factoid", "id": "622a5a7c3a8413c653000090", "snippets": [ { "offsetInBeginSection": 104, "offsetInEndSection": 156, "text": "preterm premature rupture of fetal membranes (PPROM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30957602", "endSection": "abstract" }, { "offsetInBeginSection": 171, "offsetInEndSection": 301, "text": "To examine the effect of aspirin, an anti-inflammatory agent, on the prevalence of preterm prelabor rupture of membranes (PPRoMs).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31018725", "endSection": "abstract" }, { "offsetInBeginSection": 228, "offsetInEndSection": 276, "text": " preterm prelabor rupture of membranes (PPROM). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31272257", "endSection": "abstract" }, { "offsetInBeginSection": 169, "offsetInEndSection": 215, "text": "preterm premature rupture of membranes (PPROM)", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31402735", "endSection": "abstract" }, { "offsetInBeginSection": 294, "offsetInEndSection": 440, "text": " focused on TTTS, preterm premature rupture of membranes (PPROM), pregnancy-induced hypertension (PIH), and fetal sex as possible causes of PTB.RE", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21749283", "endSection": "abstract" }, { "offsetInBeginSection": 910, "offsetInEndSection": 1397, "text": "lts: Patients with the pregnancy complicated by OHSS, had a considerably higher rate of preterm labor, whether this was labor before gestation week 37 (56.0% vs. 30.5%) or before gestation week 34 (34.0% vs. 6.8%); significantly lower weight of newborns, as in the newborns with low body weight <2500g (45.6% vs. 25.0%) and specially in the newborn with very low body weight <1500 grams (19.1% vs. 3.8%), as well as preterm premature rupture of membranes (PPROM), (11.76% vs. 1.59%).Conc", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31372118", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 167, "text": "OBJECTIVES: Preterm premature rupture of membranes (PPROM) is defined as a rupture of the amniotic membranes occurring before 37 weeks of gestation and before the onse", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23599878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Preterm premature rupture of membranes (PPROM) occurs in 1% to 2% of births. Im", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24840939", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Preterm premature rupture of membranes (PPROM) is defined as rupture of membrane that happens before the onset of labor and 37 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24304137", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "OBJECTIVES: Preterm premature rupture of membranes (PPROM) is defined as the rupture of fetal membranes befor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23573382", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "Objective: To show that infants delivered prematurely because of preterm premature rupture of the membranes (PPROM) show a tendency for asymmetric intrauterine growth retardation (IUGR). A", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10838338", "endSection": "abstract" }, { "offsetInBeginSection": 673, "offsetInEndSection": 746, "text": "ported among preterm prelabor rupture of membranes (PPROM). Educating the", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18301713", "endSection": "abstract" }, { "offsetInBeginSection": 682, "offsetInEndSection": 936, "text": "ates with PC were significantly different from controls with regard to male prevalence ( P =0.002), rates of preterm premature rupture of membranes (PPROM) ( P =0.02), longer duration of antibiotic therapy ( P =0.01) and of ventilation ( P =0.02). The di", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703979", "endSection": "abstract" }, { "offsetInBeginSection": 12, "offsetInEndSection": 162, "text": "premature rupture of membranes (PPROM) is a common condition in pregnant women and is associated with significant maternal and perinatal morbidity. Mo", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22706240", "endSection": "abstract" }, { "offsetInBeginSection": 953, "offsetInEndSection": 1137, "text": "tory response to lipopolysaccharide (LPS). This heightened response could be a critical pathway in promoting premature rupture of membranes (PPROM) and may be associated with life long", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22506729", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVES: Preterm premature rupture of membranes (PPROM) is defined as a rupture of the amniotic membranes occurring before 37 weeks of gestation and before the ons", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23599878", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Objective: To show that infants delivered prematurely because of preterm premature rupture of the membranes (PPROM) show a tendency for asymmetric intrauterine growth retardation (IUGR).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10838338", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 281, "text": "AIM: To determine whether preterm premature rupture of membranes (PPROM) before 24 weeks is an independent risk factor for poor outcome in preterm neonates.METHODS: A retrospective comparative cohort study was conducted, including viable premature infants born between 25 and 34-we", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24175963", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 383, "text": "PURPOSE: To assess prevalence and risk factors for posttraumatic stress disorder (PTSD) and depression in fathers after early preeclampsia (PE) or preterm premature rupture of membranes (PPROM).METHODS: Partners of patients hospitalized for PE or PPROM and partners of healthy controls completed PTSD (PSS-SR) and depression (BDI-II) questionnaires during pregnancy (t 1) and 6 weeks", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23179796", "endSection": "abstract" }, { "offsetInBeginSection": 1712, "offsetInEndSection": 2081, "text": "s and iatrogenic preterm delivery. In our high-risk cohort there was no gender difference for preeclampsia (RR 0.93, 95% CI 0.61 to 1.41, p\u202f=\u202f0.725) or preterm premature rupture of membranes (PPROM) (RR 1.14, 95% CI 0.86 to 1.50, p\u202f=\u202f0.384) CONCLUSIONS: In a high-risk cohort there was no significant increased risk of miscarriage, spontaneous or iatrogenic PTB, preecl", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29727785", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 158, "text": "Preterm premature rupture of membranes (PPROM) is a condition leading to an increased risk of maternal and neonatal morbidity and mortality in pregnant women.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29373884", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "UNLABELLED: Preterm premature rupture of membranes (PPROM) occurs in 3% of pregnancies and is responsible for one third of all pre", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15329560", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 147, "text": "Preterm premature rupture of the membranes (PPROM) occurs in approximately 3% of all pregnancies, and accounts for one third of all preterm births.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16118716", "endSection": "abstract" } ] }, { "body": "What is EpiMethylTag?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31752933" ], "ideal_answer": [ "EpiMethylTag is a fast, low-input, low sequencing depth method, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." ], "type": "summary", "id": "6201a20cc9dfcb9c09000027", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "EpiMethylTag: simultaneous detection of ATAC-seq or ChIP-seq signals with DNA methylation.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752933", "endSection": "title" }, { "offsetInBeginSection": 279, "offsetInEndSection": 686, "text": "We developed a fast, low-input, low sequencing depth method, EpiMethylTag, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA. Here we demonstrate that EpiMethylTag can be used to study the functional interplay between chromatin accessibility and TF binding (CTCF and KLF4) at methylated sites.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31752933", "endSection": "abstract" } ] }, { "body": "What is the target of Sutimlimab?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/29737533", "http://www.ncbi.nlm.nih.gov/pubmed/30635392", "http://www.ncbi.nlm.nih.gov/pubmed/33261023", "http://www.ncbi.nlm.nih.gov/pubmed/33512410", "http://www.ncbi.nlm.nih.gov/pubmed/34482398", "http://www.ncbi.nlm.nih.gov/pubmed/31114413", "http://www.ncbi.nlm.nih.gov/pubmed/30559259", "http://www.ncbi.nlm.nih.gov/pubmed/32176765", "http://www.ncbi.nlm.nih.gov/pubmed/31523413", "http://www.ncbi.nlm.nih.gov/pubmed/31229501", "http://www.ncbi.nlm.nih.gov/pubmed/33826820" ], "ideal_answer": [ "Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s." ], "exact_answer": [ "C1s" ], "type": "factoid", "id": "61f7cc0c882a024a1000002a", "snippets": [ { "offsetInBeginSection": 805, "offsetInEndSection": 1018, "text": "Beyond PNH, complement inhibition has also shown efficacy and safety in cold agglutinin disease (CAD), primarily with the C1s inhibitor of the classical complement pathway, sutimlimab, but also with pegcetacoplan.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34482398", "endSection": "abstract" }, { "offsetInBeginSection": 1218, "offsetInEndSection": 1369, "text": " The complement C1s inhibitor sutimlimab is an emerging option in the second line and may also find its place in the first line in specific situations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33512410", "endSection": "abstract" }, { "offsetInBeginSection": 165, "offsetInEndSection": 316, "text": "Sutimlimab, a humanized monoclonal antibody, selectively targets the C1s protein, a C1 complex serine protease responsible for activating this pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33826820", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 223, "text": "Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32176765", "endSection": "abstract" }, { "offsetInBeginSection": 257, "offsetInEndSection": 494, "text": "Therapeutic options for these complement-mediated disorders are limited and sutimlimab, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29737533", "endSection": "abstract" }, { "offsetInBeginSection": 113, "offsetInEndSection": 222, "text": "Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/32176765", "endSection": "abstract" }, { "offsetInBeginSection": 1975, "offsetInEndSection": 2205, "text": "SIONS: In patients with cold agglutinin disease who received sutimlimab, selective upstream inhibition of activity in the classic complement pathway rapidly halted hemolysis, increased hemoglobin levels, and reduced fatigue. (Fund", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33826820", "endSection": "abstract" }, { "offsetInBeginSection": 1219, "offsetInEndSection": 1369, "text": "The complement C1s inhibitor sutimlimab is an emerging option in the second line and may also find its place in the first line in specific situations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33512410", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30635392", "endSection": "title" }, { "offsetInBeginSection": 471, "offsetInEndSection": 730, "text": "In this study, we use BIVV009 (Sutimlimab), a clinical stage, humanized mAb that specifically inhibits the CP-specific serine protease C1s to evaluate the impact of upstream CP antagonism on activation and proliferation of normal and autoimmune human B cells.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30635392", "endSection": "abstract" }, { "offsetInBeginSection": 567, "offsetInEndSection": 790, "text": "Novel treatment options that target the classical complement pathway are under development and appear very promising, and the C1s inhibitor sutimlimab is currently being investigated in two clinical Phase II and III trials.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31114413", "endSection": "abstract" }, { "offsetInBeginSection": 1087, "offsetInEndSection": 1323, "text": "Of these, the anti-C1s monoclonal antibody sutimlimab has shown favorable activity in CAD, while the anti-C3 cyclic peptide pegcetacoplan appears to be promising in PNH as well as CAD, and may also have a therapeutic potential in wAIHA.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31523413", "endSection": "abstract" }, { "offsetInBeginSection": 154, "offsetInEndSection": 307, "text": "t pathway. Sutimlimab, a humanized monoclonal antibody, selectively targets the C1s protein, a C1 complex serine protease responsible for activating this", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33826820", "endSection": "abstract" }, { "offsetInBeginSection": 579, "offsetInEndSection": 802, "text": "ent options that target the classical complement pathway are under development and appear very promising, and the C1s inhibitor sutimlimab is currently being investigated in two clinical Phase II and III trials. These achie", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31114413", "endSection": "abstract" }, { "offsetInBeginSection": 261, "offsetInEndSection": 499, "text": "apeutic options for these complement-mediated disorders are limited and sutimlimab, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A ph", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29737533", "endSection": "abstract" }, { "offsetInBeginSection": 208, "offsetInEndSection": 312, "text": "is trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30559259", "endSection": "abstract" }, { "offsetInBeginSection": 477, "offsetInEndSection": 739, "text": "s study, we use BIVV009 (Sutimlimab), a clinical stage, humanized mAb that specifically inhibits the CP-specific serine protease C1s to evaluate the impact of upstream CP antagonism on activation and proliferation of normal and autoimmune human B cells. We repor", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30635392", "endSection": "abstract" }, { "offsetInBeginSection": 328, "offsetInEndSection": 526, "text": "In this phase 1 trial, we evaluated the safety and activity of BIVV009 (sutimlimab, previously TNT009), a targeted C1s inhibitor, in 10 subjects with active or past bullous pemphigoid (NCT02502903).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31229501", "endSection": "abstract" }, { "offsetInBeginSection": 374, "offsetInEndSection": 524, "text": " and activity of BIVV009 (sutimlimab, previously TNT009), a targeted C1s inhibitor, in 10 subjects with active or past bullous pemphigoid (NCT02502903", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31229501", "endSection": "abstract" }, { "offsetInBeginSection": 329, "offsetInEndSection": 479, "text": "and sutimlimab, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical comp", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/29737533", "endSection": "abstract" }, { "offsetInBeginSection": 163, "offsetInEndSection": 313, "text": ". Sutimlimab, a humanized monoclonal antibody, selectively targets the C1s protein, a C1 complex serine protease responsible for activating this pathw", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33826820", "endSection": "abstract" }, { "offsetInBeginSection": 204, "offsetInEndSection": 354, "text": ". This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. Ten patients with cold agglutinin disease ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30559259", "endSection": "abstract" }, { "offsetInBeginSection": 1257, "offsetInEndSection": 1407, "text": "cted therapies (ibrutinib, venetoclax, parsaclisib) and inhibitors of complement (sutimlimab, pegcetacoplan), spleen tyrosine kinases (fostamatinib), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33261023", "endSection": "abstract" }, { "offsetInBeginSection": 153, "offsetInEndSection": 508, "text": "nt pathway. Sutimlimab, a humanized monoclonal antibody, selectively targets the C1s protein, a C1 complex serine protease responsible for activating this pathway.METHODS: We conducted a 26-week multicenter, open-label, single-group study to assess the efficacy and safety of intravenous sutimlimab in patients with cold agglutinin disease and a recent hi", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/33826820", "endSection": "abstract" }, { "offsetInBeginSection": 206, "offsetInEndSection": 311, "text": "This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30559259", "endSection": "abstract" } ] }, { "body": "Can parasite infections by Schistosoma japonicum prevent or improve asthma?", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/31496071", "http://www.ncbi.nlm.nih.gov/pubmed/34703270", "http://www.ncbi.nlm.nih.gov/pubmed/34358648", "http://www.ncbi.nlm.nih.gov/pubmed/26840774", "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "http://www.ncbi.nlm.nih.gov/pubmed/17042799", "http://www.ncbi.nlm.nih.gov/pubmed/18654798", "http://www.ncbi.nlm.nih.gov/pubmed/18824533", "http://www.ncbi.nlm.nih.gov/pubmed/34169075" ], "ideal_answer": [ "A peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice." ], "exact_answer": "yes", "type": "yesno", "id": "622f6ad13a8413c6530000aa", "snippets": [ { "offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31496071", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/31496071", "endSection": "title" }, { "offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "endSection": "title" }, { "offsetInBeginSection": 1091, "offsetInEndSection": 1294, "text": "To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "Novel T-cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840774", "endSection": "title" }, { "offsetInBeginSection": 845, "offsetInEndSection": 1022, "text": "hese results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840774", "endSection": "abstract" }, { "offsetInBeginSection": 597, "offsetInEndSection": 843, "text": "Using a panel of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840774", "endSection": "abstract" }, { "offsetInBeginSection": 9, "offsetInEndSection": 148, "text": "Helminths and their products can regulate immune response and offer new strategies to control and alleviate inflammation, including asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34703270", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34703270", "endSection": "title" }, { "offsetInBeginSection": 149, "offsetInEndSection": 254, "text": "We previously found that a peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34703270", "endSection": "abstract" }, { "offsetInBeginSection": 608, "offsetInEndSection": 855, "text": "el of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These resul", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840774", "endSection": "abstract" }, { "offsetInBeginSection": 150, "offsetInEndSection": 268, "text": "has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma. I", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18654798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "endSection": "title" }, { "offsetInBeginSection": 1109, "offsetInEndSection": 1237, "text": "it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth inv", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "endSection": "abstract" }, { "offsetInBeginSection": 402, "offsetInEndSection": 675, "text": "s study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI).", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34169075", "endSection": "abstract" }, { "offsetInBeginSection": 152, "offsetInEndSection": 384, "text": "Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17042799", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Schistosoma japonicum infection modulates the development of allergen-induced airway inflammation in mice.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18654798", "endSection": "title" }, { "offsetInBeginSection": 147, "offsetInEndSection": 266, "text": "It has been shown that helminth infections including Schistosoma mansoni may modulate atopic diseases including asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18654798", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma.", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17042799", "endSection": "title" }, { "offsetInBeginSection": 229, "offsetInEndSection": 511, "text": "Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34169075", "endSection": "abstract" }, { "offsetInBeginSection": 1619, "offsetInEndSection": 1739, "text": "In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34169075", "endSection": "abstract" }, { "offsetInBeginSection": 512, "offsetInEndSection": 641, "text": "In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34169075", "endSection": "abstract" }, { "offsetInBeginSection": 972, "offsetInEndSection": 1122, "text": " prior to OVA immunization. These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18654798", "endSection": "abstract" }, { "offsetInBeginSection": 699, "offsetInEndSection": 849, "text": "aponicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26840774", "endSection": "abstract" }, { "offsetInBeginSection": 455, "offsetInEndSection": 605, "text": "ve found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthm", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34358648", "endSection": "abstract" }, { "offsetInBeginSection": 904, "offsetInEndSection": 1090, "text": "Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "endSection": "abstract" }, { "offsetInBeginSection": 1000, "offsetInEndSection": 1122, "text": "These results suggest that both bisexual and male S. japonicum infections may modulate the development of allergic asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18654798", "endSection": "abstract" }, { "offsetInBeginSection": 936, "offsetInEndSection": 1069, "text": "We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34169075", "endSection": "abstract" }, { "offsetInBeginSection": 1201, "offsetInEndSection": 1378, "text": "In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen-induced airway inflammation, and inhibited asthma development.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17042799", "endSection": "abstract" }, { "offsetInBeginSection": 667, "offsetInEndSection": 745, "text": "We found that S. japonicum infection downregulated airway hyperresponsiveness.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/28614408", "endSection": "abstract" }, { "offsetInBeginSection": 419, "offsetInEndSection": 655, "text": "However, in recent years, studies have found that Schistosoma infection or Schistosoma related products can improve or prevent some immune and inflammatory diseases, such as severe asthma, inflammatory bowel disease, diabetes and so on.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/34358648", "endSection": "abstract" }, { "offsetInBeginSection": 0, "offsetInEndSection": 159, "text": "In areas where schistosomiasis is endemic, a negative correlation is observed between atopy and helminth infection, associated with a low prevalence of asthma.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18824533", "endSection": "abstract" } ] }, { "body": "Describe Multilocus Inherited Neoplasia Allele Syndrome (MINAS)", "documents": [ "http://www.ncbi.nlm.nih.gov/pubmed/30580288" ], "ideal_answer": [ "Genetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations." ], "type": "summary", "id": "62059190c9dfcb9c09000034", "snippets": [ { "offsetInBeginSection": 12, "offsetInEndSection": 354, "text": "Genetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations.", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/30580288", "endSection": "abstract" } ] } ] }